Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea

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Chang-Yun Woo

2015-04-01

Full Text Available BackgroundEndogenous hyperinsulinemic hypoglycemia (EHH is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS are relatively rare.MethodsTo evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital.ResultsAmong the 84 EHH patients, 74 patients (88%, five (6%, and five (6% were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months for insulinoma, 1.0 months (range, 6 days to 7 months for nesidioblastosis, and 2.0 months (range, 1 to 12 months for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL, which suggests that these patients might have had IAS, rather than nesidioblastosis.ConclusionThe results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.

Prevention of Severe Hypoglycemia-Induced Brain Damage and Cognitive Impairment with Verapamil.

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Jackson, David A; Michael, Trevin; Vieira de Abreu, Adriana; Agrawal, Rahul; Bortolato, Marco; Fisher, Simon J

2018-05-03

People with insulin-treated diabetes are uniquely at risk for severe hypoglycemia-induced brain damage. Since calcium influx may mediate brain damage, we tested the hypothesis that the calcium channel blocker, verapamil, would significantly reduce brain damage and cognitive impairment caused by severe hypoglycemia. Ten-week-old Sprague-Dawley rats were randomly assigned to one of three treatments; 1) control hyperinsulinemic (200 mU.kg -1 min -1 ) euglycemic (80-100mg/dl) clamps (n=14), 2) hyperinsulinemic hypoglycemic (10-15mg/dl) clamps (n=16), or 3) hyperinsulinemic hypoglycemic clamps followed by a single treatment with verapamil (20mg/kg) (n=11). As compared to euglycemic controls, hypoglycemia markedly increased dead/dying neurons in the hippocampus and cortex, by 16-fold and 14-fold, respectively. Verapamil treatment strikingly decreased hypoglycemia-induced hippocampal and cortical damage, by 87% and 94%, respectively. Morris Water Maze probe trial results demonstrated that hypoglycemia induced a retention, but not encoding, memory deficit (noted by both abolished target quadrant preference and reduced target quadrant time). Verapamil treatment significantly rescued spatial memory as noted by restoration of target quadrant preference and target quadrant time. In summary, a one-time treatment with verapamil following severe hypoglycemia prevented neural damage and memory impairment caused by severe hypoglycemia. For people with insulin treated diabetes, verapamil may be a useful drug to prevent hypoglycemia-induced brain damage. © 2018 by the American Diabetes Association.

Cerebral glycogen in humans following acute and recurrent hypoglycemia: Implications on a role in hypoglycemia unawareness.

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Öz, Gülin; DiNuzzo, Mauro; Kumar, Anjali; Moheet, Amir; Khowaja, Ameer; Kubisiak, Kristine; Eberly, Lynn E; Seaquist, Elizabeth R

2017-08-01

Supercompensated brain glycogen levels may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen following RH and acute hypoglycemia (AH). After undergoing 3 hyperinsulinemic, euglycemic and 3 hyperinsulinemic, hypoglycemic clamps (RH) on separate occasions at least 1 month apart, five healthy volunteers received [1- 13 C]glucose intravenously over 80+ h while maintaining euglycemia. 13 C-glycogen levels in the occipital lobe were measured by 13 C magnetic resonance spectroscopy at ∼8, 20, 32, 44, 56, 68 and 80 h at 4 T and glycogen levels estimated by fitting the data with a biophysical model that takes into account the tiered glycogen structure. Similarly, prior 13 C-glycogen data obtained following a single hypoglycemic episode (AH) were fitted with the same model. Glycogen levels did not significantly increase after RH relative to after euglycemia, while they increased by ∼16% after AH relative to after euglycemia. These data suggest that glycogen supercompensation may be blunted with repeated hypoglycemic episodes. A causal relationship between glycogen supercompensation and generation of HAAF remains to be established.

Evaluation of the Counter-regulatory Responses to Hypoglycemia in Patients with Type 1 Diabetes during Opiate Receptor Blockade with Naltrexone

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Naik, Sarita; Belfort-DeAguiar, Renata; Sejling, Anne-Sophie

2017-01-01

AIMS: Hypoglycemia is the major limiting factor in achieving optimal glycemic control in people with type 1 diabetes (T1DM), especially intensively treated patients with impaired glucose counterregulation during hypoglycemia. Naloxone, an opiate receptor blocker, has been reported to enhance...... with a high risk for hypoglycemia. MATERIALS AND METHODS: We performed a randomized, placebo-controlled, double-blinded, cross-over study in which 9 intensively treated subjects with T1DM underwent a 2-step euglycemic-hypoglycemic-hyperinsulinemic clamp on two separate occasions. Twelve hours and 1 hour...

Congenital hyperinsulinism: current trends in diagnosis and therapy

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Bellanné-Chantelot Christine

2011-10-01

Full Text Available Abstract Congenital hyperinsulinism (HI is an inappropriate insulin secretion by the pancreatic β-cells secondary to various genetic disorders. The incidence is estimated at 1/50, 000 live births, but it may be as high as 1/2, 500 in countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed because of seizures, a faint, or any other neurological symptom, in the neonatal period or later, usually within the first two years of life. After the neonatal period, the patient can present the typical clinical features of a hypoglycemia: pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main clinically indistinguishable histopathological lesions: diffuse and focal. Atypical lesions are under characterization. Recessive ABCC8 mutations (encoding SUR1, subunit of a potassium channel and, more rarely, recessive KCNJ11 (encoding Kir6.2, subunit of the same potassium channel mutations, are responsible for most severe diazoxide-unresponsive HI. Focal HI, also diazoxide-unresponsive, is due to the combination of a paternally-inherited ABCC8 or KCNJ11 mutation and a paternal isodisomy of the 11p15 region, which is specific to the islets cells within the focal lesion. Genetics and 18F-fluoro-L-DOPA positron emission tomography (PET help to diagnose diffuse or focal forms of HI. Hypoglycemias must be rapidly and intensively treated to prevent severe and irreversible brain damage. This includes a glucose load and/or a glucagon injection, at the time of hypoglycemia, to correct it. Then a treatment to prevent the recurrence of hypoglycemia must be set, which may include frequent and glucose-enriched feeding, diazoxide and octreotide. When medical and dietary therapies are ineffective, or when a focal HI is suspected, surgical treatment is required. Focal HI may be definitively cured when the partial pancreatectomy removes the whole lesion. By

An uncommon cause of hypoglycemia: insulin autoimmune syndrome.

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Savas-Erdeve, Senay; Yılmaz Agladioglu, Sebahat; Onder, Asan; Peltek Kendirci, Havva Nur; Bas, Veysel Nijat; Sagsak, Elif; Cetinkaya, Semra; Aycan, Zehra

2014-01-01

Insulin autoimmune syndrome (IAS) is a condition characterized by hypoglycemia associated with the presence of autoantibodies to insulin in patients who have not been injected with insulin. A female patient (aged 16 years and 3 months) presented with the complaint of being overweight. Physical examination revealed a body weight of 78.2 kg (+2.6 SD) and a height of 167 cm (+0.73 SD). While the patient's fasting blood glucose level was found to be 40 mg/dl, blood ketone was negative and the serum insulin level was determined as 379 mIU/ml. The patient was diagnosed with hyperinsulinemic hypoglycemia. Abdominal ultrasound, pancreas MRI and endoscopic ultrasound were normal. The daily blood glucose profile revealed postprandial hyperglycemia and reactive hypoglycemia in addition to fasting hypoglycemia. The results of anti-insulin antibody measurements were as high as 41.8% (normal range 0-7%). A 1,600-calorie diet containing 40% carbohydrate and divided into 6 meals a day was given to the patient. Simple sugars were excluded from the diet. Hypoglycemic episodes were not observed, but during 2 years of observation, serum levels of insulin and anti-insulin antibodies remained elevated. In all hyperinsulinemic hypoglycemia cases, IAS should be considered in the differential diagnosis and insulin antibody measurements should be carried out. © 2014 S. Karger AG, Basel.

Postprandial hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass

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Øhrstrøm, Caroline Christfort; Worm, Dorte; Hansen, Dorte Lindqvist

2017-01-01

of developing hypoglycemia. Known risk factors are female sex, longer time since surgery, and lack of prior diabetes. Management of the hypoglycemic episodes is difficult, and only dietary modifications consisting of frequent and less carbohydrate-rich meals seem to be efficient. Medical treatments and surgical...

Recurrent antecedent hypoglycemia alters neuronal oxidative metabolism in vivo.

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Jiang, Lihong; Herzog, Raimund I; Mason, Graeme F; de Graaf, Robin A; Rothman, Douglas L; Sherwin, Robert S; Behar, Kevin L

2009-06-01

The objective of this study was to characterize the changes in brain metabolism caused by antecedent recurrent hypoglycemia under euglycemic and hypoglycemic conditions in a rat model and to test the hypothesis that recurrent hypoglycemia changes the brain's capacity to utilize different energy substrates. Rats exposed to recurrent insulin-induced hypoglycemia for 3 days (3dRH rats) and untreated controls were subject to the following protocols: [2-(13)C]acetate infusion under euglycemic conditions (n = 8), [1-(13)C]glucose and unlabeled acetate coinfusion under euglycemic conditions (n = 8), and [2-(13)C]acetate infusion during a hyperinsulinemic-hypoglycemic clamp (n = 8). In vivo nuclear magnetic resonance spectroscopy was used to monitor the rise of(13)C-labeling in brain metabolites for the calculation of brain metabolic fluxes using a neuron-astrocyte model. At euglycemia, antecedent recurrent hypoglycemia increased whole-brain glucose metabolism by 43 +/- 4% (P glucose utilization in neurons. Although acetate metabolism remained the same, control and 3dRH animals showed a distinctly different response to acute hypoglycemia: controls decreased pyruvate dehydrogenase (PDH) flux in astrocytes by 64 +/- 20% (P = 0.01), whereas it increased by 37 +/- 3% in neurons (P = 0.01). The 3dRH animals decreased PDH flux in both compartments (-75 +/- 20% in astrocytes, P neurons, P = 0.005). Thus, acute hypoglycemia reduced total brain tricarboxylic acid cycle activity in 3dRH animals (-37 +/- 4%, P = 0.001), but not in controls. Our findings suggest that after antecedent hypoglycemia, glucose utilization is increased at euglycemia and decreased after acute hypoglycemia, which was not the case in controls. These findings may help to identify better methods of preserving brain function and reducing injury during acute hypoglycemia.

Effects of hypoglycemia on human brain activation measured with fMRI.

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Anderson, Adam W; Heptulla, Rubina A; Driesen, Naomi; Flanagan, Daniel; Goldberg, Philip A; Jones, Timothy W; Rife, Fran; Sarofin, Hedy; Tamborlane, William; Sherwin, Robert; Gore, John C

2006-07-01

Functional magnetic resonance imaging (fMRI) was used to measure the effects of acute hypoglycemia caused by passive sensory stimulation on brain activation. Visual stimulation was used to generate blood-oxygen-level-dependent (BOLD) contrast, which was monitored during hyperinsulinemic hypoglycemic and euglycemic clamp studies. Hypoglycemia (50 +/- 1 mg glucose/dl) decreased the fMRI signal relative to euglycemia in 10 healthy human subjects: the fractional signal change was reduced by 28 +/- 12% (P variations in blood glucose levels may modulate BOLD signals in the healthy brain.

The action of diazoxide and minoxidil sulphate on rat blood vessels: a comparison with cromakalim.

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Newgreen, D. T.; Bray, K. M.; McHarg, A. D.; Weston, A. H.; Duty, S.; Brown, B. S.; Kay, P. B.; Edwards, G.; Longmore, J.; Southerton, J. S.

1990-01-01

1. The actions of diazoxide and minoxidil sulphate have been compared with those of cromakalim in rat aorta and portal vein. 2. Diazoxide and minoxidil sulphate hyperpolarized the rat portal vein in a similar manner to cromakalim. 3. Cromakalim, diazoxide and minoxidil sulphate increased 42K and 86Rb efflux from rat portal vein, although minoxidil sulphate had only a small effect on 86Rb efflux. 4. Cromakalim, diazoxide and minoxidil sulphate increased 42K efflux from rat aorta but only cromakalim and diazoxide increased 86Rb efflux from this tissue. 5. Glibenclamide inhibited the relaxant actions of cromakalim, diazoxide and minoxidil sulphate on rat aorta and the increase in 42K efflux produced by these agents in this tissue. 6. Diazoxide relaxed an 80 mM KCl-induced contraction of rat aorta, whilst cromakalim and minoxidil sulphate were without effect. 7. Cromakalim, diazoxide and minoxidil sulphate had no effect on cyclic AMP or cyclic GMP concentrations in rat aorta. 8. It is concluded that diazoxide and minoxidil sulphate like cromakalim exhibit K+ channel opening properties in vascular smooth muscle. Diazoxide exerts an additional inhibitory action not related to the production of cyclic AMP or cyclic GMP. The action of minoxidil sulphate may be primarily located at a K+ channel which is relatively impermeable to 86Rb. PMID:2167738

Acute phase response in lactating dairy cows during hyperinsulinemic hypoglycaemic and hyperinsulinemic euglycaemic clamps and after intramammary LPS challenge.

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De Matteis, L; Bertoni, G; Lombardelli, R; Wellnitz, O; Van Dorland, H A; Vernay, M C M B; Bruckmaier, R M; Trevisi, E

2017-06-01

The link between energy availability, turnover of energy substrates and the onset of inflammation in dairy cows is complex and poorly investigated. To clarify this, plasma inflammatory variables were measured in mid-lactating dairy cows allocated to three groups: hyperinsulinemic hypoglycaemic clamp, induced by insulin infusion (HypoG, n = 5); hyperinsulinemic euglycaemic clamp, induced by insulin and glucose infusion (EuG; n = 6); control, receiving a saline solution infusion (NaCl; n = 6). At 48 h after the start of i.v. infusions, two udder quarters per cow were challenged with 200 μg of E. coli lipopolysaccharide (LPS). Individual blood samples were taken before clamps, before LPS challenge (i.e. 48 h after clamps) and 6.5 h after. At 48 h, positive acute phase proteins (posAPP) did not differ among groups, whereas albumin and cholesterol (index of lipoproteins), negative APP (negAPP), were lower (p insulin at the tissue-level makes dairy cows more susceptible to inflammatory events. In contrast, HypoG seems to attenuate the inflammatory response. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Severe hypoglycemia secondary to methimazole-induced insulin autoimmune syndrome in a 16 year old African-American male.

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Gomez Cruz, Michelle J; Jabbar, Muhammad; Saini, Natinder; Eng, Donna; Crawford, Brandon; Vazquez, Delia M; Menon, Ram; Chen, Ming

2012-12-01

Insulin autoimmune syndrome (IAS) or Hirata's disease is a rare disorder characterized by hypoglycemia secondary to insulin autoantibodies (IAb). Over 200 patients have been described from Japan with significantly less numbers being reported from outside the Orient. IAS is more common in patients older than 40 yr of age with reports in the pediatric age group being notably rarer. Exposure to sulfhydryl group containing medications is implicated in the pathogenesis of this syndrome. In this report, we describe a case of IAS in an African-American adolescent. A 16-yr-old healthy African-American male was diagnosed with Graves' disease and started on Methimazole. Four weeks later, he was found unconscious and hypoglycemic (blood sugar 1.5 mmol/L). Evaluation was negative for insulinoma. Insulin antibodies were positive. Oral glucose tolerance test revealed elevated free insulin concentrations with disproportionately elevated total insulin levels. The patient was started on prednisone, diazoxide, and propranolol for management of IAS and hyperthyroidism. Thyroid radio-ablation was subsequently undertaken. The doses of prednisone and diazoxide were tapered and these medications discontinued after 9 months. The insulin antibody levels decreased gradually and became undetectable in 6 months with resolution of the hypoglycemia. © 2012 John Wiley & Sons A/S.

Tolbutamide attenuates diazoxide-induced aggravation of hypoxic cell injury.

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Pissarek, M; Reichelt, C; Krauss, G J; Illes, P

1998-11-23

ATP-dependent potassium (KATP) channels of neurons are closed in the presence of physiological levels of intracellular ATP and open when ATP is depleted during hypoxia or metabolic damage. The present study investigates hypoxic alterations of purine and pyrimidine nucleotide levels supposed to intracellularly modulate KATP channels. In addition, the effects of the KATP channel activator diazoxide and its antagonist tolbutamide were investigated on ATP, GTP, CTP and UTP levels in slices of the parietal cortex. Hypoxia was evoked by saturation of the medium with 95% N2-5% CO2 instead of 95% O2-5% CO2 for 5 min. Nucleotide contents were measured by anion-exchange HPLC in neutralized perchloric acid extracts obtained from slices frozen immediately at the end of incubation. Hypoxia per se decreased purine and pyrimidine nucleoside triphosphate contents. Thus, ATP and GTP contents were reduced to 69.9 and 77.6% of the respective normoxic levels. UTP and CTP contents were even more decreased (to 60.9 and 41.6%),, probably because the salvage pathway of these pyrimidine nucleotides is less effective than that of the purine nucleotides ATP and GTP. While tolbutamide (30 microM) had no effect on the hypoxia-induced decrease of nucleotides, diazoxide at 300, but not 30 microM aggravated the decline of ATP, UTP and CTP to 51.8, 37.5 and 28.5% of the contents observed at normoxia; GTP levels also showed a tendency to decrease after diazoxide application. Tolbutamide (300 microM) antagonized the effects of diazoxide (300 but not 30 microM aggravated the decline of ATP, UTP and CTP to 51.8, 37.5 and 28.5% of the contents observed at normoxia; GTP levels also showed a tendency to decrease after diazoxide application. Tolbutamide (300 microM) antagonized the effects of diazoxide (300 MicroM). Nucleoside diphosphate (ADP, GDP and UDP) levels were uniformly increased by hypoxia. There was no hypoxia-induced increase of ADP contents in the presence of tolbutamide (300 microM). The ATP

Management of Refractory Noninsulinoma Pancreatogenous Hypoglycemia Syndrome with Gastric Bypass Reversal: A Case Report and Review of the Literature

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Bhavana B. Rao

2015-01-01

Full Text Available Background. Roux-en-Y gastric bypass (RYGB is a commonly performed, effective bariatric procedure; however, rarely, complications such as postprandial hypoglycemia due to noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS may ensue. Management of refractory NIPHS is challenging. We report a case that was successfully treated with RYGB reversal. Case Report. A 58-year-old male with history of RYGB nine months earlier for morbid obesity presented for evaluation of postprandial, hypoglycemic seizures. Testing for insulin level, insulin antibodies, oral hypoglycemic agents, pituitary axis hormone levels, and cortisol stimulation was unrevealing. Computed tomography (CT scan of the abdomen was unremarkable. A 72-hour fast was completed without hypoglycemia. Mixed meal testing demonstrated endogenous hyperinsulinemic hypoglycemia (EHH and selective arterial calcium stimulation testing (SACST was positive. Strict dietary modifications, maximal medical therapy, gastrostomy tube feeding, and stomal reduction failed to alleviate symptoms. Ultimately, he underwent laparoscopic reversal of RYGB. Now, 9 months after reversal, he has markedly reduced hypoglycemia burden. Discussion. Hyperfunctioning islets secondary to exaggerated incretin response and altered intestinal nutrient delivery are hypothesized to be causative in NIPHS. For refractory cases, there is increasing skepticism about the safety and efficacy of pancreatic resection. RYGB reversal may be successful.

Clopidogrel-Induced Insulin Autoimmune Syndrome: A Newly Recognized Cause of Hypoglycemia in a Patient Without Diabetes.

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Rajpal, Aman; Kassem, Laure Sayyed; Moscoso-Cordero, Maria; Arafah, Baha M

2017-09-01

Insulin autoimmune syndrome (IAS), defined as hyperinsulinemic hypoglycemia with high titers of anti-insulin antibodies, is frequently reported in Japanese patients but rarely observed in whites. We report in this study on a 79-year-old white male without diabetes who developed IAS following exposure to clopidogrel, a drug not previously known to cause hypoglycemia. The patient presented with recurrent symptomatic hypoglycemia. During one episode, serum glucose was 45 mg/dL, whereas insulin and C-peptide levels were 40,000 mIU/mL and 40 ng/mL, respectively. Additional studies revealed no intake of insulin or its secretagogues, whereas anti-insulin antibody titer was high (59.3 nmol/L). Although total insulin levels were consistently high, free insulin concentrations (polyethylene glycol precipitation) were appropriate for ambient glycemia. The patient was found to have HLA-DRB1*0404, a feature often reported in Japanese patients with IAS. Three weeks prior to symptom onset, he was started on clopidogrel, a drug that does not have a sulfhydryl group, but its active metabolite does. Clopidogrel was switched to a nonsulfhydryl antiplatelet agent, and glucocorticoid therapy was initiated. Shortly thereafter, the frequency of hypoglycemic episodes decreased, and glucocorticoids were tapered over the ensuing 3 months. No hypoglycemic episodes were noted during 6 months of observation after discontinuing glucocorticoids, whereas the total insulin and anti-insulin antibody levels normalized. The data indicate that IAS should be considered in the differential diagnosis of hyperinsulinemic hypoglycemia in seemingly well individuals, even when no drugs known to cause IAS were used. Clinical suspicion of IAS can avoid expensive imaging and unnecessary surgery in affected patients.

Hypoinsulinemic hypoglycemia triggered by liver injury in elderly subjects with low body weight: case reports

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Takatoshi Anno

2018-03-01

Full Text Available Hypoglycemia is induced by many causes, especially over-dose of insulin or oral hypoglycemic agents in diabetic subjects. In such a case, hyperinsulinemic hypoglycemia is usually observed. On the other hand, it is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia. Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in clinical practice. Herein, we experienced similar 2 cases of non-diabetic hypoinsulinemic hypoglycemia. Both of them were elderly subjects with low body weight. Furthermore, it is likely that hypoinsulinemic hypoglycemia in both subjects was triggered by severe liver injury, at least in part, due to possible limited liver glycogen store. In elderly subjects with low body weight and/or malnutrition, metabolism in the liver is reduced and glycogen accumulation is decreased. Such alteration brings out acute and marked liver injury, which finally leads to the onset of severe hypoglycemia. It is known that not only liver injury but also multiple organ failure could be induced due to extreme emaciation in subjects. It is likely that in elderly subjects with low body weight and/or malnutrition, multiple organ failure including liver failure could be induced due to the similar reason. Therefore, we should be very careful of such subjects in order to avoid the development of multiple organ failure which leads to life-threatening situations. In conclusion, we should keep in mind the possibility of hypoinsulinemic hypoglycemia when we examine severe liver injury, especially in elderly or starving subjects with low body weight and limited liver glycogen stores.

Prophylactic Dextrose Gel Does Not Prevent Neonatal Hypoglycemia: A Quasi-Experimental Pilot Study.

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Coors, Sarah M; Cousin, Joshua J; Hagan, Joseph L; Kaiser, Jeffrey R

2018-03-28

To test the hypothesis that prophylactic dextrose gel administered to newborn infants at risk for hypoglycemia will increase the initial blood glucose concentration after the first feeding and decrease neonatal intensive care unit (NICU) admissions for treatment of asymptomatic neonatal hypoglycemia compared with feedings alone. This quasi-experimental study allocated asymptomatic at-risk newborn infants (late preterm, birth weight 4000 g, and infants of mothers with diabetes) to receive prophylactic dextrose gel (Insta-Glucose; Valeant Pharmaceuticals North America LLC, Bridgewater, New Jersey); other at-risk infants formed the control group. After the initial feeding, the prophylactic group received dextrose gel (0.5 mL/kg) rubbed into the buccal mucosa. The blood glucose concentration was checked 30 minutes later. Initial glucose concentrations and rate of NICU admissions were compared between the prophylactic group and controls using bivariate analyses. A multivariable linear regression compared first glucose concentrations between groups, adjusting for at-risk categories and age at first glucose concentration. There were 236 subjects (72 prophylactic, 164 controls). The first glucose concentration was not different between the prophylactic and control groups in bivariate analysis (52.1 ± 17.1 vs 50.5 ± 15.3 mg/dL, P = .69) and after adjusting for covariates (P  = .18). Rates of NICU admission for treatment of transient neonatal hypoglycemia were 9.7% and 14.6%, respectively (P = .40). Prophylactic dextrose gel did not reduce transient neonatal hypoglycemia or NICU admissions for hypoglycemia. The carbohydrate concentration of Insta-Glucose (77%) may have caused a hyperinsulinemic response, or alternatively, exogenous enteral dextrose influences glucose homeostasis minimally during the first few hours when counter-regulatory mechanisms are especially active. ClinicalTrials.gov: NCT02523222. Copyright © 2018 Elsevier Inc. All

Hypoinsulinemic hypoglycemia triggered by liver injury in elderly subjects with low body weight: case reports.

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Anno, Takatoshi; Kaneto, Hideaki; Shigemoto, Ryo; Kawasaki, Fumiko; Kawai, Yasuhiro; Urata, Noriyo; Kawamoto, Hirofumi; Kaku, Kohei; Okimoto, Niro

2018-01-01

Hypoglycemia is induced by many causes, especially over-dose of insulin or oral hypoglycemic agents in diabetic subjects. In such a case, hyperinsulinemic hypoglycemia is usually observed. On the other hand, it is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia. Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in clinical practice. Herein, we experienced similar 2 cases of non-diabetic hypoinsulinemic hypoglycemia. Both of them were elderly subjects with low body weight. Furthermore, it is likely that hypoinsulinemic hypoglycemia in both subjects was triggered by severe liver injury, at least in part, due to possible limited liver glycogen store. In elderly subjects with low body weight and/or malnutrition, metabolism in the liver is reduced and glycogen accumulation is decreased. Such alteration brings out acute and marked liver injury, which finally leads to the onset of severe hypoglycemia. It is known that not only liver injury but also multiple organ failure could be induced due to extreme emaciation in subjects. It is likely that in elderly subjects with low body weight and/or malnutrition, multiple organ failure including liver failure could be induced due to the similar reason. Therefore, we should be very careful of such subjects in order to avoid the development of multiple organ failure which leads to life-threatening situations. In conclusion, we should keep in mind the possibility of hypoinsulinemic hypoglycemia when we examine severe liver injury, especially in elderly or starving subjects with low body weight and limited liver glycogen stores. It is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia.Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in everyday clinical practice.Herein, we reported similar 2 cases of hypoinsulinemic hypoglycemia without diabetes presumably triggered

Plasma glucagon and glucose recovery after hypoglycemia

DEFF Research Database (Denmark)

Hilsted, J; Frandsen, Henrik Lund; Holst, Janett

1991-01-01

) and of isolated alpha-adrenergic blockade on hormonal responses to hypoglycemia and on blood glucose recovery after hypoglycemia in healthy subjects. Neither of the pharmacological blockades had any significant effects on plasma glucagon responses to hypoglycemia nor had they any effect on the rate of blood...... glucose recovery after hypoglycemia. We conclude that the autonomic nervous system has no major influence on the glucagon response to hypoglycemia in healthy man. Changes in autonomic nervous activity are not essential for blood glucose recovery after hypoglycemia in healthy man....

Effects of Sleep Deprivation on Hypoglycemia-Induced Cognitive Impairment and Recovery in Adults With Type 1 Diabetes.

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Inkster, Berit E; Zammitt, Nicola N; Ritchie, Stuart J; Deary, Ian J; Morrison, Ian; Frier, Brian M

2016-05-01

To ascertain whether hypoglycemia in association with sleep deprivation causes greater cognitive dysfunction than hypoglycemia alone and protracts cognitive recovery after normoglycemia is restored. Fourteen adults with type 1 diabetes underwent a hyperinsulinemic, hypoglycemic clamp on two separate occasions. Before one glucose clamp, the participants stayed awake overnight to induce sleep deprivation. Participants were randomized and counterbalanced to the experimental condition. Cognitive function tests were performed before and during hypoglycemia and for 90 min after restoration of normoglycemia. Cognitive impairment during hypoglycemia did not differ significantly between the sleep-deprived and non-sleep-deprived conditions. However, in the sleep-deprived state, digit symbol substitution scores and choice reaction times were significantly poorer during recovery (P sleep deprivation, such as tiredness, were removed. Hypoglycemia per se produced a significant decrement in cognitive function; coexisting sleep deprivation did not have an additive effect. However, after restoration of normoglycemia, preceding sleep deprivation was associated with persistence of hypoglycemic symptoms and greater and more prolonged cognitive dysfunction during the recovery period. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

The Impact of Nocturnal Hypoglycemia on Sleep in Subjects With Type 2 Diabetes

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Jennum, Poul; Stender-Petersen, Kirstine; Rabøl, Rasmus

2015-01-01

night visits (one normoglycemic and one hypoglycemic) in randomized order. Plasma glucose (PG) levels were controlled by hyperinsulinemic glucose clamping. On the hypoglycemic night, hypoglycemia was induced after reaching sleep stage N2 by turning off glucose infusion until the PG target of 2......OBJECTIVE: The aim of this trial was to investigate the impact of nocturnal hypoglycemia on sleep patterns (assessed by polysomnography) and counterregulatory hormones. RESEARCH DESIGN AND METHODS: In this single-blinded, crossover trial, 26 subjects with type 2 diabetes attended two experimental.......7-2.8 mmol/L was reached and maintained for 15 min. Thereafter, subjects were brought back to normoglycemia for the rest of the night. On the normoglycemic night, PG was maintained at 5.0-7.0 mmol/L throughout the night. RESULTS: During the first 4 h of sleep (0-4 h; after reaching sleep stage N2...

Defective awakening response to nocturnal hypoglycemia in patients with type 1 diabetes mellitus.

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Bernd Schultes

2007-02-01

Full Text Available BACKGROUND: Nocturnal hypoglycemia frequently occurs in patients with type 1 diabetes mellitus (T1DM. It can be fatal and is believed to promote the development of the hypoglycemia-unawareness syndrome. Whether hypoglycemia normally provokes awakening from sleep in individuals who do not have diabetes, and whether this awakening response is impaired in T1DM patients, is unknown. METHODS AND FINDINGS: We tested two groups of 16 T1DM patients and 16 healthy control participants, respectively, with comparable distributions of gender, age, and body mass index. In one night, a linear fall in plasma glucose to nadir levels of 2.2 mmol/l was induced by infusing insulin over a 1-h period starting as soon as polysomnographic recordings indicated that stage 2 sleep had been reached. In another night (control, euglycemia was maintained. Only one of the 16 T1DM patients, as compared to ten healthy control participants, awakened upon hypoglycemia (p = 0.001. In the control nights, none of the study participants in either of the two groups awakened during the corresponding time. Awakening during hypoglycemia was associated with increased hormonal counterregulation. In all the study participants (from both groups who woke up, and in five of the study participants who did not awaken (three T1DM patients and two healthy control participants, plasma epinephrine concentration increased with hypoglycemia by at least 100% (p < 0.001. A temporal pattern was revealed such that increases in epinephrine in all participants who awakened started always before polysomnographic signs of wakefulness (mean +/- standard error of the mean: 7.5 +/- 1.6 min. CONCLUSIONS: A fall in plasma glucose to 2.2 mmol/l provokes an awakening response in most healthy control participants, but this response is impaired in T1DM patients. The counterregulatory increase in plasma epinephrine that we observed to precede awakening suggests that awakening forms part of a central nervous system

Monogenic hyperinsulinemic hypoglycemia: current insights into the pathogenesis and management

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Lord Katherine

2013-02-01

Full Text Available Abstract Hyperinsulinism (HI is the leading cause of persistent hypoglycemia in children, which if unrecognized may lead to development delays and permanent neurologic damage. Prompt recognition and appropriate treatment of HI are essential to avoid these sequelae. Major advances have been made over the past two decades in understanding the molecular basis of hyperinsulinism and mutations in nine genes are currently known to cause HI. Inactivating KATP channel mutations cause the most common and severe type of HI, which occurs in both a focal and a diffuse form. Activating mutations of glutamate dehydrogenase (GDH lead to hyperinsulinism/hyperammonemia syndrome, while activating mutations of glucokinase (GK, the “glucose sensor” of the beta cell, causes hyperinsulinism with a variable clinical phenotype. More recently identified genetic causes include mutations in the genes encoding short-chain 3-hydroxyacyl-CoA (SCHAD, uncoupling protein 2 (UCP2, hepatocyte nuclear factor 4-alpha (HNF-4α, hepatocyte nuclear factor 1-alpha (HNF-1α, and monocarboyxlate transporter 1 (MCT-1, which results in a very rare form of HI triggered by exercise. For a timely diagnosis, a critical sample and a glucagon stimulation test should be done when plasma glucose is ATP channel agonist, suggests a KATP defect, which frequently requires pancreatectomy. Surgery is palliative for children with diffuse KATPHI, but children with focal KATPHI are cured with a limited pancreatectomy. Therefore, distinguishing between diffuse and focal disease and localizing the focal lesion in the pancreas are crucial aspects of HI management. Since 2003, 18 F-DOPA PET scans have been used to differentiate diffuse and focal disease and localize focal lesions with higher sensitivity and specificity than more invasive interventional radiology techniques. Hyperinsulinism remains a challenging disorder, but recent advances in the understanding of its genetic basis and breakthroughs in

Hypoglycemia-associated changes in the electroencephalogram in patients with type 1 diabetes and normal hypoglycemia awareness or unawareness

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Sejling, Anne-Sophie; Kjær, Troels W; Pedersen-Bjergaard, Ulrik

2015-01-01

Hypoglycemia is associated with increased activity in the low-frequency bands in the electroencephalogram (EEG). We investigated whether hypoglycemia awareness and unawareness are associated with different hypoglycemia-associated EEG changes in patients with type 1 diabetes.Twenty-four patients...... and hypoglycemia symptom scores were recorded and the counterregulatory hormonal response was measured.Quantitative EEG analysis showed that the absolute amplitude of the theta band and alpha-theta band up to doubled during hypoglycemia with no difference between the two groups. In the recovery period the theta...

Hyperinsulinaemic hypoglycaemia in Beckwith-Wiedemann syndrome (BWS) due to defects in the function of pancreatic ß-cell ATP-sensitive K+ channels

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Hussain, K; Cosgrove, K E; Shepherd, R M

2005-01-01

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is clinically and genetically heterogeneous. Hyperinsulinemic hypoglycemia occurs in about 50% of children with BWS and, in the majority of infants, it resolves spontaneously. However, in a small group of patients...... the hypoglycemia can be persistent and may require pancreatectomy. The mechanism of persistent hyperinsulinemic hypoglycemia in this group of patients is unclear....

Glucose-Dependent Insulinotropic Polypeptide Augments Glucagon Responses to Hypoglycemia in Type 1 Diabetes

DEFF Research Database (Denmark)

Christensen, Mikkel; Calanna, Salvatore; Sparre-Ulrich, Alexander H

2015-01-01

constituted a "recovery phase." During the recovery phase, GIP infusions elicited larger glucagon responses (164 ± 50 [GIP] vs. 23 ± 25 [GLP-1] vs. 17 ± 46 [saline] min ⋅ pmol/L, P endogenous glucose production was higher with GIP and lower with GLP-1 compared with saline (P ... days, significantly less exogenous glucose was needed to keep plasma glucose above 2 mmol/L (155 ± 36 [GIP] vs. 232 ± 40 [GLP-1] vs. 212 ± 56 [saline] mg ⋅ kg(-1), P ... similar on all days. Our results suggest that during hypoglycemia in patients with T1DM, exogenous GIP increases glucagon responses during the recovery phase after hypoglycemia and reduces the need for glucose administration....

[Sudden death from hypoglycemia].

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Asmundo, A; Aragona, M; Gualniera, P; Aragona, F

1995-12-01

The sudden death by hypoglycemia is an aspect of the forensic pathology frequently neglected. Authors initially described the pathogenesis of different hypoglycemia forms, distinguishing the primary ones due to hyperinsulinism and the secondary ones due to functional insufficiency of other organs (hypophysis, thyroid, adrenal gland, liver); after that Authors described three cases of sudden death induced hypoglycemia by hyperinsulinism: two were unweaned with nesidioblastosis and one adolescent. In any form of hypoglycemia the central nervous system damage is present with evident neuronal degenerative-necrotic phenomena, widespread edema with microhemorrhage, swollen and dissociation of myelin sheath, glial cells hyperplasia. Death caused by primary hypoglycemia is histopathologically different from the secondary one because of the maintenance of hepatic glycogen content in the former, that increase in striated muscles, including the heart, in spite of the constant secretion of catecholamine from the adrenal medulla. Glycogen is depleted in secondary hypoglycemia. In the primary form, behind the adrenal medulla hyperfunction, the increased functional activity of the adrenal cortex is moderate, contrasting with the seriousness of the syndrome, due prevalently to inhibit the gluconeogenesis response conditioned by the persistence of stored glycogen in the liver, heart and striated muscles. The rare anoxic processes coming with resynthesis of hepatic glycogen have to be considered in the differential diagnosis. The primary hypoglycemic death, especially in unweaned, is frequently promoted by other processes inducing hypoxia (fetal asphyxia outcome, pneumonia, etc.) or worsening the hypoglycemia (hypothyroidism, etc.). The secondary hypoglycemias are characterized by the normality of exocrine pancreas and by organic alterations that cause glycogen depletion from the liver.

Rat liver responsiveness to gluconeogenic substrates during insulin-induced hypoglycemia

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H.M. de Souza

2001-06-01

Full Text Available Hepatic responsiveness to gluconeogenic substrates during insulin-induced hypoglycemia was investigated. For this purpose, livers were perfused with a saturating concentration of 2 mM glycerol, 5 mM L-alanine or 5 mM L-glutamine as gluconeogenic substrates. All experiments were performed 1 h after an ip injection of saline (CN group or 1 IU/kg of insulin (IN group. The IN group showed higher (P<0.05 hepatic glucose production from glycerol, L-alanine and L-glutamine and higher (P<0.05 production of L-lactate, pyruvate and urea from L-alanine and L-glutamine. In addition, ip injection of 100 mg/kg glycerol, L-alanine and L-glutamine promoted glucose recovery. The results indicate that the hepatic capacity to produce glucose from gluconeogenic precursors was increased during insulin-induced hypoglycemia.

Hypothalamic Obesity following Craniopharyngioma Surgery: Results of a Pilot Trial of Combined Diazoxide and Metformin Therapy

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Ahmet Alexandra

2011-03-01

Full Text Available Objective. To assess the effect of combined diazoxide-metformin therapy in obese adolescents treated for craniopharyngioma. Design. A prospective open-label 6-month pilot treatment trial in 9 obese subjects with craniopharyngioma. Diazoxide (2 mg/kg divided b.i.d., maximum 200 mg/day and metformin (1000 mg b.i.d.. Whole body insulin sensitivity index (WBISI and area-under-the-curve insulin (AUCins were calculated. Results. Seven subjects completed: 4M/3F, mean ± SD age years, weight  kg, BMI  kg/m2, and BMI SDS . Two were withdrawn due to vomiting and peripheral edema. Of participants completing the study, the mean ± SD weight gain, BMI, and BMI SDS during the 6 months were reduced compared to the 6 months prestudy ( versus  kg, ; versus  kg/m2, ; versus , , resp.. AUCins correlated with weight loss (, and BMI decrease (, . Conclusion. Combined diazoxide-metformin therapy was associated with reduced weight gain in patients with hypothalamic obesity. AUCins at study commencement predicted effectiveness of the treatment.

Hypopituitarism in a patient with Beckwith-Wiedemann syndrome due to hypomethylation of KvDMR1.

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Baiocchi, Michela; Yousuf, Fatimah Sireen; Hussain, Khalid

2014-04-01

Beckwith-Wiedemann syndrome (BWS) is caused by dysregulation of imprinted genes on chromosome 11.p15.5. The syndrome includes overgrowth, macroglossia, organomegaly, abdominal wall defects, hypoglycemia, and long-term malignancy risk. No patient who has BWS has been reported with hypopituitarism. We describe a patient who presented at birth with macrosomia, macroglossia, respiratory distress, jaundice, and hypoglycemia, and who was followed for 4.5 years. Genetic test for BWS was performed, which detected loss of maternal methylation on region KvDMR1 (11p15.5). The hypoglycemia was attributable to hyperinsulinism and was treated with diazoxide and chlorothiazide. She responded well, but the hypoglycemia returned after reducing the diazoxide. It was possible to stop the diazoxide after 2.5 years. On routine follow-up she was noted to be developing short stature. Baseline pituitary and growth hormone (GH) stimulation tests detected GH deficiency and secondary hypothyroidism. A brain MRI showed a small anterior pituitary gland. Thereafter, thyroxine and replacement therapy with GH were started, which resulted in a remarkable improvement in growth velocity. This is the first patient to be reported as having hypopituitarism and BWS. It is unclear if the BWS and the hypopituitarism are somehow connected; however, further investigations are necessary. Hypopituitarism explains the protracted hypoglycemia and the short stature. In our patient, GH therapy seems to be safe, but strict follow-up is required given the increased cancer risk related to BWS.

Diabetic Hypoglycemia

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Diabetic hypoglycemia Overview For people with diabetes, low blood sugar (hypoglycemia) occurs when there's too much insulin ... your blood sugar into a normal range. Untreated, diabetic hypoglycemia can lead to seizures and loss of ...

Octreotide therapy and restricted fetal growth

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Geilswijk, Marianne; Andersen, Lise Lotte Torvin; Frost, Morten

2017-01-01

that octreotide treatment in pregnancy, as well as hypoglycemia in itself, may pose a risk of fetal growth restriction. During pregnancy, management of blood glucose levels in familial hyperinsulinemic hypoglycemia thus forms a medical dilemma. We report on pregnancy outcomes in a woman with symptomatic familial...... hyperinsulinemic hypoglycemia, type 3. During the patient's first pregnancy with a viable fetus octreotide treatment was instituted in gestational age 23 weeks to prevent severe hypoglycemic incidences. Fetal growth velocity declined, and at 37 weeks of gestation, intrauterine growth retardation was evident...... growth velocity was normal. We conclude that octreotide treatment during pregnancy may pose a risk of fetal growth restriction and warrants careful consideration. In some cases of familial hyperinsulinemic hypoglycemia, blood glucose levels can be successfully managed through diet only, also during...

Near-total pancreatectomy for persistent hyperinsulinemic ...

African Journals Online (AJOL)

of persistent hypoglycemia in infancy with consequences ... (PHHI) is the most common cause of recurrent and per- sistent hypoglycemia in infancy and childhood. Causes .... a high rate of pancreatic surgery in the neonatal-onset group.

Whole genome expression profiling associates activation of unfolded protein response with impaired production and release of epinephrine after recurrent hypoglycemia.

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Juhye Lena Kim

Full Text Available Recurrent hypoglycemia can occur as a major complication of insulin replacement therapy, limiting the long-term health benefits of intense glycemic control in type 1 and advanced type 2 diabetic patients. It impairs the normal counter-regulatory hormonal and behavioral responses to glucose deprivation, a phenomenon known as hypoglycemia associated autonomic failure (HAAF. The molecular mechanisms leading to defective counter-regulation are not completely understood. We hypothesized that both neuronal (excessive cholinergic signaling between the splanchnic nerve fibers and the adrenal medulla and humoral factors contribute to the impaired epinephrine production and release in HAAF. To gain further insight into the molecular mechanism(s mediating the blunted epinephrine responses following recurrent hypoglycemia, we utilized a global gene expression profiling approach. We characterized the transcriptomes during recurrent (defective counter-regulation model and acute hypoglycemia (normal counter-regulation group in the adrenal medulla of normal Sprague-Dawley rats. Based on comparison analysis of differentially expressed genes, a set of unique genes that are activated only at specific time points after recurrent hypoglycemia were revealed. A complementary bioinformatics analysis of the functional category, pathway, and integrated network indicated activation of the unfolded protein response. Furthermore, at least three additional pathways/interaction networks altered in the adrenal medulla following recurrent hypoglycemia were identified, which may contribute to the impaired epinephrine secretion in HAAF: greatly increased neuropeptide signaling (proenkephalin, neuropeptide Y, galanin; altered ion homeostasis (Na+, K+, Ca2+ and downregulation of genes involved in Ca2+-dependent exocytosis of secretory vesicles. Given the pleiotropic effects of the unfolded protein response in different organs, involved in maintaining glucose homeostasis, these

Hyperinsulinism associated with gestational exposure to bupropion in a newborn infant.

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Gisslen, Tate; Nathan, Brandon; Thompson, Theodore; Rao, Raghavendra

2011-01-01

This case report describes severe hyperinsulinism in a term newborn infant without typical perinatal risk factors for transient hyperinsulinism. The mother had received bupropion, an antidepressant and aid to smoking cessation, throughout pregnancy. The infant presented with profound hypoglycemia and seizures on the 3rd day of life. Laboratory investigation confirmed hyperinsulinism. Stable euglycemia could be achieved only after starting diazoxide. The infant was weaned from diazoxide by 10 weeks of age without recurrence of hypoglycemia, signifying the transient nature of hyperinsulinism. This is the first reported case of a potential association between maternal bupropion use during pregnancy and neonatal hyperinsulinism, and highlights the importance of close monitoring of similar infants.

Spontaneous Hypoglycemia After Islet Autotransplantation for Chronic Pancreatitis.

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Lin, Yu Kuei; Faiman, Charles; Johnston, Philip C; Walsh, R Matthew; Stevens, Tyler; Bottino, Rita; Hatipoglu, Betul A

2016-10-01

Spontaneous hypoglycemia has been reported in patients after total pancreatectomy (TP) and islet autotransplantation (IAT) with maintained insulin independence. Details surrounding these events have not been well described. The objective of the study was to determine the frequency and characteristics of spontaneous hypoglycemia in patients undergoing TP-IAT and/or to ascertain predictive or protective factors of its development. This was an observational cohort study in 40 patients who underwent TP-IAT from August 2008 to May 2014, with a median follow-up of 34 months. The study was conducted at a single institution (Cleveland Clinic). Patients included recipients of TP-IAT. The intervention included small, frequent meals in those patients who developed spontaneous hypoglycemia. Incidence of spontaneous hypoglycemia development, characteristics of the patients developing hypoglycemia, and their response to small, frequent meals were measured. Six of 12 patients, who maintained insulin independence, developed spontaneous hypoglycemia. The episodes could be fasting, postprandial, and/or exercise associated, with the frequency ranging from two to three times daily to once every 1-2 weeks. All patients experienced at least one episode that required external assistance, glucagon administration, and/or emergent medical attention. Patients who developed hypoglycemia had a lower median age and tended to have a lower median islet equivalent/kg body weight but a higher median total islet equivalent, body mass index, and homeostatic model assessment for insulin resistance score. All patients who received small, frequent meal intervention had improvement in severity and/or frequency of the hypoglycemic episodes. Spontaneous hypoglycemia is prevalent after TP-IAT. Although the underlying pathophysiology responsible for these hypoglycemia events remains to be elucidated, small, frequent meal intervention is helpful in ameliorating this condition.

Effect of oral amino acids on counterregulatory responses and cognitive function during insulin-induced hypoglycemia in nondiabetic and type 1 diabetic people.

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Rossetti, Paolo; Porcellati, Francesca; Busciantella Ricci, Natalia; Candeloro, Paola; Cioli, Patrizia; Nair, K Sreekumaran; Santeusanio, Fausto; Bolli, Geremia B; Fanelli, Carmine G

2008-07-01

Amino acids stimulate glucagon responses to hypoglycemia and may be utilized by the brain. The aim of this study was to assess the responses to hypoglycemia in nondiabetic and type 1 diabetic subjects after ingestion of an amino acid mixture. Ten nondiabetic and 10 diabetic type 1 subjects were studied on three different occasions during intravenous insulin (2 mU . kg(-1) . min(-1)) plus variable glucose for 160 min. In two studies, clamped hypoglycemia (47 mg/dl plasma glucose for 40 min) was induced and either oral placebo or an amino acid mixture (42 g) was given at 30 min. In the third study, amino acids were given, but euglycemia was maintained. Plasma glucose and insulin were no different in the hypoglycemia studies with both placebo and amino acids (P > 0.2). After the amino acid mixture, plasma amino acid concentrations increased to levels observed after a mixed meal (2.4 +/- 0.13 vs. placebo study 1.7 +/- 0.1 mmol/l, P = 0.02). During clamped euglycemia, ingestion of amino acids resulted in transient increases in glucagon concentrations, which returned to basal by the end of the study. During clamped hypoglycemia, glucagon response was sustained and increased more in amino acid studies versus placebo in nondiabetic and diabetic subjects (P colored words, and verbal memory tests for nondiabetic subjects; and Trail-Making part B, digit span backward, and Stroop color tests for diabetic subjects. Oral amino acids improve cognitive function in response to hypoglycemia and enhance the response of glucagon in nondiabetic and diabetic subjects.

Hypoglycemia.

Science.gov (United States)

Alsahli, Mazen; Gerich, John E

2013-12-01

Hypoglycemia remains a common problem for patients with diabetes and is associated with substantial morbidity and mortality. This article summarizes our current knowledge of the epidemiology, pathogenesis, risk factors, and complications of hypoglycemia in patients with diabetes and discusses prevention and treatment strategies. Copyright © 2013 Elsevier Inc. All rights reserved.

Weight loss in obese men by caloric restriction and high-dose diazoxide-mediated insulin suppression.

NARCIS (Netherlands)

Boekel, G.A.J van; Loves, S.; Sorge, A.A. van; Ruinemans-Koerts, J.; Rijnders, T.; Boer, H. de

2008-01-01

OBJECTIVE: To examine the concept whether high-dose diazoxide (DZX)-mediated insulin suppression, in combination with moderate caloric restriction and increased physical activity, can establish a weight loss of at least 15% in obese hyperinsulinaemic men. DESIGN: Open, uncontrolled, 6-month pilot

Severe hypoglycemia, impaired awareness of hypoglycemia, and self-monitoring in adults with type 1 diabetes

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Hendrieckx, Crystal; Jenkins, A; Hagger, Virginia

2017-01-01

AIMS: To assess prevalence of severe hypoglycemia, awareness and symptoms of hypoglycemia, and their associations with self-monitoring of blood glucose. METHODS: Diabetes MILES-Australia Study participants completed validated questionnaires and study-specific items. RESULTS: Of 642 adults with ty...... autonomic symptoms, perceived at relatively low glucose levels. Frequent self-monitoring of blood glucose prompted early recognition and treatment of hypoglycemia, suggesting severe hypoglycemia risk can be minimized.......AIMS: To assess prevalence of severe hypoglycemia, awareness and symptoms of hypoglycemia, and their associations with self-monitoring of blood glucose. METHODS: Diabetes MILES-Australia Study participants completed validated questionnaires and study-specific items. RESULTS: Of 642 adults with type...

Posttranscriptional regulation of adrenal TH gene expression contributes to the maladaptive responses triggered by insulin-induced recurrent hypoglycemia.

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Kudrick, Necla; Chan, Owen; La Gamma, Edmund F; Kim, Juhye Lena; Tank, Arnold William; Sterling, Carol; Nankova, Bistra B

2015-02-01

Acute metabolic stress such as insulin-induced hypoglycemia triggers a counterregulatory response during which the release of catecholamines (epinephrine), the activation of tyrosine hydroxylase (TH) enzyme and subsequent compensatory catecholamine biosynthesis occur in the adrenal medulla. However, recurrent exposure to hypoglycemia (RH), a consequence of tight glycemic control in individuals with type 1 and type 2 diabetes compromises this physiological response. The molecular mechanisms underlying the maladaptive response to repeated glucose deprivation are incompletely understood. We hypothesize that impaired epinephrine release following RH reflects altered regulation of adrenal catecholamine biosynthesis. To test this hypothesis, we compared the effect of single daily (RH) and twice-daily episodes of insulin-induced hypoglycemia (2RH) on adrenal epinephrine release and production in normal rats. Control animals received saline injections under similar conditions (RS and 2RS, respectively). Following 3 days of treatment, we assessed the counterregulatory hormonal responses during a hypoglycemic clamp. Changes in adrenal TH gene expression were also analyzed. The counterregulatory responses, relative TH transcription and TH mRNA levels and Ser40-TH phosphorylation (marker for enzyme activation) were induced to a similar extent in RS, 2RS, and RH groups. In contrast, epinephrine and glucagon responses were attenuated in the 2RH group and this was associated with a limited elevation of adrenal TH mRNA, rapid inactivation of TH enzyme and no significant changes in TH protein. Our results suggest that novel posttranscriptional mechanisms controlling TH mRNA and activated TH enzyme turnover contribute to the impaired epinephrine responses and may provide new therapeutic targets to prevent HAAF. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Hypoglycemia: Role of Hypothalamic Glucose-Inhibited (GI) Neurons in Detection and Correction.

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Zhou, Chunxue; Teegala, Suraj B; Khan, Bilal A; Gonzalez, Christina; Routh, Vanessa H

2018-01-01

Hypoglycemia is a profound threat to the brain since glucose is its primary fuel. As a result, glucose sensors are widely located in the central nervous system and periphery. In this perspective we will focus on the role of hypothalamic glucose-inhibited (GI) neurons in sensing and correcting hypoglycemia. In particular, we will discuss GI neurons in the ventromedial hypothalamus (VMH) which express neuronal nitric oxide synthase (nNOS) and in the perifornical hypothalamus (PFH) which express orexin. The ability of VMH nNOS-GI neurons to depolarize in low glucose closely parallels the hormonal response to hypoglycemia which stimulates gluconeogenesis. We have found that nitric oxide (NO) production in low glucose is dependent on oxidative status. In this perspective we will discuss the potential relevance of our work showing that enhancing the glutathione antioxidant system prevents hypoglycemia associated autonomic failure (HAAF) in non-diabetic rats whereas VMH overexpression of the thioredoxin antioxidant system restores hypoglycemia counterregulation in rats with type 1 diabetes.We will also address the potential role of the orexin-GI neurons in the arousal response needed for hypoglycemia awareness which leads to behavioral correction (e.g., food intake, glucose administration). The potential relationship between the hypothalamic sensors and the neurocircuitry in the hindbrain and portal mesenteric vein which is critical for hypoglycemia correction will then be discussed.

Hypoglycemia: Role of Hypothalamic Glucose-Inhibited (GI Neurons in Detection and Correction

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Chunxue Zhou

2018-03-01

Full Text Available Hypoglycemia is a profound threat to the brain since glucose is its primary fuel. As a result, glucose sensors are widely located in the central nervous system and periphery. In this perspective we will focus on the role of hypothalamic glucose-inhibited (GI neurons in sensing and correcting hypoglycemia. In particular, we will discuss GI neurons in the ventromedial hypothalamus (VMH which express neuronal nitric oxide synthase (nNOS and in the perifornical hypothalamus (PFH which express orexin. The ability of VMH nNOS-GI neurons to depolarize in low glucose closely parallels the hormonal response to hypoglycemia which stimulates gluconeogenesis. We have found that nitric oxide (NO production in low glucose is dependent on oxidative status. In this perspective we will discuss the potential relevance of our work showing that enhancing the glutathione antioxidant system prevents hypoglycemia associated autonomic failure (HAAF in non-diabetic rats whereas VMH overexpression of the thioredoxin antioxidant system restores hypoglycemia counterregulation in rats with type 1 diabetes.We will also address the potential role of the orexin-GI neurons in the arousal response needed for hypoglycemia awareness which leads to behavioral correction (e.g., food intake, glucose administration. The potential relationship between the hypothalamic sensors and the neurocircuitry in the hindbrain and portal mesenteric vein which is critical for hypoglycemia correction will then be discussed.

Induced hypoglycemia for 48 hours indicates differential glucose and insulin effects on liver metabolism in dairy cows.

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Kreipe, L; Vernay, M C M B; Oppliger, A; Wellnitz, O; Bruckmaier, R M; van Dorland, H A

2011-11-01

Hypoglycemia is a characteristic condition of early lactation dairy cows and is subsequently dependent on, and may affect, metabolism in the liver. The objective of the present study was to investigate the effects of induced hypoglycemia, maintained for 48 h, on metabolic parameters in plasma and liver of mid-lactation dairy cows. The experiment involved 3 treatments, including a hyperinsulinemic hypoglycemic clamp (HypoG, n=6) to obtain a glucose concentration of 2.5 mmol/L, a hyperinsulinemic euglycemic clamp (EuG, n=6) in which the effect of insulin was studied, and a control treatment with a 0.9% saline solution (NaCl, n=6). Blood samples for measurements of insulin, metabolites, and enzymes were taken at least once per hour. Milk yield was recorded and milk samples were collected before and after treatment. Liver biopsies were obtained before and after treatment to measure mRNA abundance by real-time, quantitative reverse transcription-PCR of 12 candidate genes involved in the main metabolic pathways. Milk yield decreased in HypoG and NaCl cows, whereas it remained unaffected in EuG cows. Energy-corrected milk yield (kg/d) was only decreased in HypoG cows. In plasma, concentration of β-hydroxybutyrate decreased in response to treatment in EuG cows and was lower (0.41±0.04 mmol/L) on d 2 of the treatment compared with that in HypoG and NaCl cows (on average 0.61±0.03 mmol/L, respectively). Nonesterified fatty acids remained unaffected in all treatments. In the liver, differences between treatments for their effects were only observed in case of mitochondrial phosphoenolpyruvate carboxykinase (PEPCKm) and glucose-6-phosphatase (G6PC). In HypoG, mRNA abundance of PEPCKm was upregulated, whereas in EuG and NaCl cows, it was downregulated. The EuG treatment downregulated mRNA expression of G6PC, a marked effect compared with the unchanged transcript expression in NaCl. The mRNA abundance of the insulin receptor remained unaffected in all treatments, and no

Hypoglycemia in Coffin-Siris syndrome.

Science.gov (United States)

Imaizumi, K; Nakamura, M; Masuno, M; Makita, Y; Kuroki, Y

1995-10-23

We describe a further patient with the Coffin-Siris syndrome who presented at 4 months with recurrent hypoglycemia attacks. Detailed examination was undertaken at 7 months but the cause of hypoglycemia was not detected. Hypoglycemia seems to be a previously undescribed finding in the Coffin-Siris syndrome.

Reporting Severe Hypoglycemia in Type 1 Diabetes

DEFF Research Database (Denmark)

Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2017-01-01

PURPOSE OF REVIEW: To describe potential factors influencing reporting of severe hypoglycemia in adult patients with type 1 diabetes and to analyze their effect on reported rates of severe hypoglycemia. RECENT FINDINGS: Reported rates of severe hypoglycemia defined as need for third party...... by partners report higher rates of severe hypoglycemia. There is a large variation between studies reporting incidence and prevalence of severe hypoglycemia in patients with type 1 diabetes, mainly explained by definition of severity, methods of reporting, and patient selection. These findings call...... hypoglycemia are 0.02-0.5 events per patient-year and 1-29%, respectively. When subjects with recurrent severe hypoglycemia in the past or suffering from impaired hypoglycemia awareness are excluded from participation in studies, lower rates are reported. Studies applying anonymous reporting or reporting...

Hypoglycemia in type 2 diabetes: Standpoint of an experts′ committee (India hypoglycemia study group

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Mohan Viswanathan

2012-01-01

Full Text Available The epidemic of type 2 diabetes and the recognition that achieving specific glycemic goals can substantially reduce morbidity have made the effective treatment of hyperglycemia a top priority. Despite compelling evidence that tight glycemic control is crucial for delaying disease progression, increased risk of hypoglycemia associated with such control underscore the complexity of diabetes management. In most cases, hypoglycemia results from an excess of insulin, either absolute or relative to the available glucose substrate and the factors perhaps exacerbating the risk are pharmacokinetic imperfections, behavioral, co-morbidities etc. Additionally, many patients remain undiagnosed, and many diagnosed patients are not treated appropriately. In this article, the challenges of hypoglycemia, confronting health care providers and their patients with diabetes, are discussed for making treatment decisions that will help minimize risk of hypoglycemia and eventually overcome formidable barriers to optimal diabetes management. Strategies to treat and minimize the frequency and severity of hypoglycemia without compromising on glycemic goals are also presented.

Autoimmune Hypoglycemia in Type 1 Diabetes Mellitus.

Science.gov (United States)

Ambigapathy, Jayakumar; Sahoo, Jayaprakash; Kamalanathan, Sadishkumar

2017-07-15

Antibodies against exogenous insulin are common in type 1 diabetes mellitus patients. They can cause hypoglycemia, albeit uncommonly. A 14-year-old girl with type 1 diabetes mellitus presented with recurrent hypoglycemia. High insulin, low C-peptide and raised insulin antibody levels documented during hypoglycemia. Plasmapheresis led to remission of hypoglycemia. Antibodies to exogenous insulin should be considered as a cause of recurrent refractory hypoglycemia in type 1 diabetes mellitus patients.

Effect of Diazoxide Preconditioning on Cultured Rat Myocardium Microvascular Endothelial Cells against Apoptosis and Relation of PI3K/Akt Pathway

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Cao Su

2014-03-01

Full Text Available Background: Anti-apoptotic mechanism for cell protection on reperfusion may provide a new method to reduce reperfusion injury. Aims: The aim of the present study is to explore the effect of mitochondrial ATP sensitive potassium channel (Mito-KATP opener diazoxide (DZ preconditioning on hypoxia/ reoxygen (H/R injury of rat myocardium microvascular endothelial cells (MMECs against apoptosis and relation of PI3K/Akt pathway. Study Design: Animal experimentation. Methods: The rat MMECs were cultivated, and H/R model was made to imitate ischemia-reperfusion injury. The cells were seeds in 96-wellplates (100μL/hole or in 6cm diameter dishes (2 mL/dish with the density of 1×106/mL and randomly divided into 4 groups (n=6 each: control group (Group N, hypoxia-regoxygen group (Group H/R, Diazoxide preconditioning+H/R group (Group DZ and Diazoxide preconditioning +mitochondrial KATP blocker 5-hydroxydecanoate (5-HD + H/R group (Group DZ+5-HD. The cells were exposed to 2h hypoxia followed by 2h reoxygenation. Diazoxide 100μmol/L and diazoxide 100μmol/L+ 5-HD100μmol/L were added to the culture medium 2h before hypoxia in DZ and DZ+5-HD groups respectively. Each group was observed the proliferation in MTT, apoptotic rate in Annexin V-FITC/PI double standard, cell structure of Hoechst staining, and the levels of PI3K, Akt and p53 mRNA by RT-qPCR. Results: Compared with Group N, apoptotic rate of Group H/R increased (p<0.01 and the vitality decreased significantly (p<0.05, and the expression of PI3K, Akt and p53 mRNA elevated in Group H/R (p<0.05. Compared with Group H/R, apoptotic rate and p53 mRNA level of Group DZ depressed significantly (p<0.01, p<0.05, while the vitality, PI3K and Akt mRNA levels increased (p<0.05. Compared with Group DZ, apoptotic rate and p53 mRNA level of Group DZ+5-HD increased significantly (p<0.01, p<0.05, but the vitality, PI3K and Akt mRNA levels decreased (p<0.05. Conclusion: Under the condition of H/R, mito-KATP opened by DZ

Role of insulin in the hyperandrogenemia of lean women with polycystic ovary syndrome and normal insulin sensitivity.

Science.gov (United States)

Baillargeon, Jean-Patrice; Carpentier, André

2007-10-01

To determine the effect of reducing insulin secretion on hyperandrogenemia in lean normoinsulinemic women with polycystic ovary syndrome (PCOS) and normal metabolic insulin sensitivity. Transversal assessment at baseline and prospective follow-up of lean PCOS group after 8 days of diazoxide, which reduces insulin secretion, and 1 month of leuprolide, which suppresses LH. Clinical research center of an academic hospital. Nine lean women (body mass index PCOS and normal insulin levels, as well as 17 lean healthy women. Lean PCOS women were reassessed after 8 days of diazoxide and after 1 month of leuprolide, which suppresses LH. Androgen levels and insulin-stimulated glucose disposal (metabolic insulin sensitivity), determined by euglycemic-hyperinsulinemic clamp (M-value). Mean M-value of lean PCOS women (48.5 micromol/kg.min) was similar to lean control subjects (52.9 micromol/kg.min). They also had comparable anthropometric measures, lipids, fibrinogen, and plasminogen activator inhibitor 1. The LH did not change significantly after diazoxide, but was almost suppressed after leuprolide in the PCOS group. Androstenedione decreased significantly after diazoxide and even more after leuprolide. However, free T significantly decreased only after diazoxide in lean PCOS women. Diazoxide also increased SHBG significantly in this group. In women with typical PCOS and normal insulin levels and metabolic insulin sensitivity, reducing insulin secretion significantly decreased androgen and increased SHBG levels. These results suggest that insulin contributes to hyperandrogenemia even in PCOS women with normal metabolic insulin sensitivity, which might be due to increased sensitivity of their androgenic insulin pathway.

Patient Understanding of Hypoglycemia in Tertiary Referral Centers

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Nan Hee Cho

2018-02-01

Full Text Available BackgroundHypoglycemia is an important complication in the treatment of patients with diabetes. We surveyed the insight by patients with diabetes into hypoglycemia, their hypoglycemia avoidance behavior, and their level of worry regarding hypoglycemia.MethodsA survey of patients with diabetes, who had visited seven tertiary referral centers in Daegu or Gyeongsangbuk-do, Korea, between June 2014 and June 2015, was conducted. The survey contained questions about personal history, symptoms, educational experience, self-management, and attitudes about hypoglycemia.ResultsOf 758 participants, 471 (62.1% had experienced hypoglycemia, and 250 (32.9% had experienced hypoglycemia at least once in the month immediately preceding the study. Two hundred and forty-two (31.8% of the participants had received hypoglycemia education at least once, but only 148 (19.4% knew the exact definition of hypoglycemia. Hypoglycemic symptoms identified by the participants were dizziness (55.0%, sweating (53.8%, and tremor (40.8%. They mostly chose candy (62.1%, chocolate (37.7%, or juice (36.8% as food for recovering hypoglycemia. Participants who had experienced hypoglycemia had longer duration of diabetes and a higher proportion of insulin usage. The mean scores for hypoglycemia avoidance behavior and worry about hypoglycemia were 21.2±10.71 and 23.38±13.19, respectively. These scores tended to be higher for participants with higher than 8% of glycosylated hemoglobin, insulin use, and experience of emergency room visits.ConclusionMany patients had experienced hypoglycemia and worried about it. We recommend identifying patients that are anxious about hypoglycemia and educating them about what to do when they develop hypoglycemic symptoms, especially those who have a high risk of hypoglycemia.

Patient Understanding of Hypoglycemia in Tertiary Referral Centers.

Science.gov (United States)

Cho, Nan Hee; Kim, Nam Kyung; Han, Eugene; Hong, Jun Hwa; Jeon, Eon Ju; Moon, Jun Sung; Seo, Mi Hae; Lee, Ji Eun; Seo, Hyun Ae; Kim, Mi Kyung; Kim, Hye Soon

2018-02-01

Hypoglycemia is an important complication in the treatment of patients with diabetes. We surveyed the insight by patients with diabetes into hypoglycemia, their hypoglycemia avoidance behavior, and their level of worry regarding hypoglycemia. A survey of patients with diabetes, who had visited seven tertiary referral centers in Daegu or Gyeongsangbuk-do, Korea, between June 2014 and June 2015, was conducted. The survey contained questions about personal history, symptoms, educational experience, self-management, and attitudes about hypoglycemia. Of 758 participants, 471 (62.1%) had experienced hypoglycemia, and 250 (32.9%) had experienced hypoglycemia at least once in the month immediately preceding the study. Two hundred and forty-two (31.8%) of the participants had received hypoglycemia education at least once, but only 148 (19.4%) knew the exact definition of hypoglycemia. Hypoglycemic symptoms identified by the participants were dizziness (55.0%), sweating (53.8%), and tremor (40.8%). They mostly chose candy (62.1%), chocolate (37.7%), or juice (36.8%) as food for recovering hypoglycemia. Participants who had experienced hypoglycemia had longer duration of diabetes and a higher proportion of insulin usage. The mean scores for hypoglycemia avoidance behavior and worry about hypoglycemia were 21.2±10.71 and 23.38±13.19, respectively. These scores tended to be higher for participants with higher than 8% of glycosylated hemoglobin, insulin use, and experience of emergency room visits. Many patients had experienced hypoglycemia and worried about it. We recommend identifying patients that are anxious about hypoglycemia and educating them about what to do when they develop hypoglycemic symptoms, especially those who have a high risk of hypoglycemia. Copyright © 2018 Korean Diabetes Association

Norepinephrine kinetics during insulin-induced hypoglycemia

DEFF Research Database (Denmark)

Hilsted, J; Christensen, N J; Larsen, S

1985-01-01

Norepinephrine (NE) kinetics (plasma appearance rate, clearance, and forearm extraction) were measured during insulin-induced hypoglycemia in six healthy subjects. NE clearance did not change during hypoglycemia, indicating that the increase in plasma NE during hypoglycemia is due to an increased...

Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal.

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Goldfine, A B; Mun, E C; Devine, E; Bernier, R; Baz-Hecht, M; Jones, D B; Schneider, B E; Holst, J J; Patti, M E

2007-12-01

Hyperinsulinemic hypoglycemia is newly recognized as a rare but important complication after Roux-en-Y gastric bypass (GB). The etiology of the syndrome and metabolic characteristics remain incompletely understood. Recent studies suggest that levels of incretin hormones are increased after GB and may promote excessive beta-cell function and/or growth. We performed a cross-sectional analysis of metabolic variables, in both the fasting state and after a liquid mixed-meal challenge, in four subject groups: 1) with clinically significant hypoglycemia [neuroglycopenia (NG)] after GB surgery, 2) with no symptoms of hypoglycemia at similar duration after GB surgery, 3) without GB similar to preoperative body mass index of the surgical cohorts, and 4) without GB similar to current body mass index of the surgical cohorts. Insulin and C-peptide after the liquid mixed meal were both higher relative to the glucose level achieved in persons after GB with NG compared with asymptomatic individuals. Glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide levels were higher in both post-GB surgical groups compared with both overweight and morbidly obese persons, and glucagon-like peptide 1 was markedly higher in the group with NG. Insulin resistance, assessed by homeostasis model assessment of insulin resistance, the composite insulin sensitivity index, or adiponectin, was similar in both post-GB groups. Dumping score was also higher in both GB groups but did not discriminate between asymptomatic and symptomatic patients. Notably, the frequency of asymptomatic hypoglycemia after a liquid mixed meal was high in post-GB patients. A robust insulin secretory response was associated with postprandial hypoglycemia in patients after GB presenting with NG. Increased incretin levels may contribute to the increased insulin secretory response.

Prevention of hypoglycemia-induced neuronal death by minocycline

Science.gov (United States)

2012-01-01

Diabetic patients who attempt strict management of blood glucose levels frequently experience hypoglycemia. Severe and prolonged hypoglycemia causes neuronal death and cognitive impairment. There is no effective tool for prevention of these unwanted clinical sequelae. Minocycline, a second-generation tetracycline derivative, has been recognized as an anti-inflammatory and neuroprotective agent in several animal models such as stroke and traumatic brain injury. In the present study, we tested whether minocycline also has protective effects on hypoglycemia-induced neuronal death and cognitive impairment. To test our hypothesis we used an animal model of insulin-induced acute hypoglycemia. Minocycline was injected intraperitoneally at 6 hours after hypoglycemia/glucose reperfusion and injected once per day for the following 1 week. Histological evaluation for neuronal death and microglial activation was performed from 1 day to 1 week after hypoglycemia. Cognitive evaluation was conducted 6 weeks after hypoglycemia. Microglial activation began to be evident in the hippocampal area at 1 day after hypoglycemia and persisted for 1 week. Minocycline injection significantly reduced hypoglycemia-induced microglial activation and myeloperoxidase (MPO) immunoreactivity. Neuronal death was significantly reduced by minocycline treatment when evaluated at 1 week after hypoglycemia. Hypoglycemia-induced cognitive impairment is also significantly prevented by the same minocycline regimen when subjects were evaluated at 6 weeks after hypoglycemia. Therefore, these results suggest that delayed treatment (6 hours post-insult) with minocycline protects against microglial activation, neuronal death and cognitive impairment caused by severe hypoglycemia. The present study suggests that minocycline has therapeutic potential to prevent hypoglycemia-induced brain injury in diabetic patients. PMID:22998689

Rituximab induced hypoglycemia in non-Hodgkin's lymphoma

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Lali V

2006-12-01

Full Text Available Abstract Background Hypoglycemia is a vary rare toxicity of rituximab. The exact mechanism of rituximab induced hypoglycemia is not clear. Case presentation A 50 year old female presented with a left tonsillar non Hodgkin's lymphoma and was started on R-CHOP chemotherapy. Twenty four hours after the first rituximab infusion, she developed hypoglycemia which was managed by IV glucose infusion. Conclusion Hypoglycemia following rituximab administration is rare. Possibilities of hypoglycemia should be kept in mind in patients developing symptoms like fatigue, restlessness, and sweating while on rituximab therapy.

Individual and societal consequences of hypoglycemia

DEFF Research Database (Denmark)

Dømgaard, Mikala; Bagger, Malene; Rhee, Nicolai Alexander

2015-01-01

BACKGROUND: Hypoglycemia and fear of hypoglycemia threaten individuals' ability to work and drive. We studied the effect of hypoglycemia on the individual and society, with a focus on possible implications of new European union legislation on patients' continued ability to drive. METHODS: A cross......-sectional survey of Danish Diabetes Association members was conducted to investigate individual and societal consequences of hypoglycemia. RESULTS: A total of 3117/9951 individuals with type 1 diabetes (T1DM) (32.2%) or type 2 diabetes (T2DM) (67.8%) completed the survey. The calculated incidence rates of self...

Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery.

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Duarte, João M N; Morgenthaler, Florence D; Gruetter, Rolf

2017-06-01

Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.

Interdisciplinary approach to compensation of hypoglycemia in diabetic patients with chronic heart failure.

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Anfinogenova, Yana; Grakova, Elena V; Shvedova, Maria; Kopieva, Kristina V; Teplyakov, Alexander T; Popov, Sergey V

2018-05-01

Diabetes mellitus is a chronic disease requiring lifelong control with hypoglycemic agents that must demonstrate excellent efficacy and safety profiles. In patients taking glucose-lowering drugs, hypoglycemia is a common cause of death associated with arrhythmias, increased thrombus formation, and specific effects of catecholamines due to sympathoadrenal activation. Focus is now shifting from merely glycemic control to multifactorial approach. In the context of individual drugs and classes, this article reviews interdisciplinary strategies evaluating metabolic effects of drugs for treatment of chronic heart failure (CHF) which can mask characteristic hypoglycemia symptoms. Hypoglycemia unawareness and cardiac autonomic neuropathy are discussed. Data suggesting that hypoglycemia modulates immune response are reviewed. The potential role of gut microbiota in improving health of patients with diabetes and CHF is emphasized. Reports stating that nondiabetic CHF patients can have life-threatening hypoglycemia associated with imbalance of thyroid hormones are discussed. Regular glycemic control based on HbA1c measurements and adequate pharmacotherapy remain the priorities in diabetes management. New antihyperglycemic drugs with safer profiles should be preferred in vulnerable CHF patients. Multidrug interactions must be considered. Emerging therapies with reduced hypoglycemia risk, telemedicine, sensor technologies, and genetic testing predicting hypoglycemia risk may help solving the challenges of hypoglycemia in CHF patients with diabetes. Interdisciplinary work may involve cardiologists, diabetologists/endocrinologists, immunologists, gastroenterologists, microbiologists, nutritionists, imaging specialists, geneticists, telemedicine experts, and other relevant specialists. This review emphasizes that systematic knowledge on pathophysiology of hypoglycemia in diabetic patients with CHF is largely lacking and the gaps in our understanding require further discoveries.

Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies.

Science.gov (United States)

Rooijackers, Hanne M M; Wiegers, Evita C; Tack, Cees J; van der Graaf, Marinette; de Galan, Bastiaan E

2016-02-01

Hypoglycemia is the most frequent complication of insulin therapy in patients with type 1 diabetes. Since the brain is reliant on circulating glucose as its main source of energy, hypoglycemia poses a threat for normal brain function. Paradoxically, although hypoglycemia commonly induces immediate decline in cognitive function, long-lasting changes in brain structure and cognitive function are uncommon in patients with type 1 diabetes. In fact, recurrent hypoglycemia initiates a process of habituation that suppresses hormonal responses to and impairs awareness of subsequent hypoglycemia, which has been attributed to adaptations in the brain. These observations sparked great scientific interest into the brain's handling of glucose during (recurrent) hypoglycemia. Various neuroimaging techniques have been employed to study brain (glucose) metabolism, including PET, fMRI, MRS and ASL. This review discusses what is currently known about cerebral metabolism during hypoglycemia, and how findings obtained by functional and metabolic neuroimaging techniques contributed to this knowledge.

Effect of Insulin Therapy using Hyper-insulinemic Normoglycemic Clamp on Inflammatory Response in Brain Dead Organ Donors.

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Aljiffry, M; Hassanain, M; Schricker, T; Shaheen, M; Nouh, T; Lattermann, R; Salman, A; Wykes, L; Metrakos, P

2016-05-01

Brain death is a major stress that is associated with a massive inflammatory response and systemic hyperglycemia. Severe inflammation leads to increased graft immunogenicity and risk of graft dysfunction; while acute hyperglycemia aggravates the inflammatory response and increases the risk of morbidity and mortality. Insulin therapy not only controls hyperglycemia but also suppresses inflammation. The present study is to investigate the anti-inflammatory properties and the normoglycemia maintenance of high dose insulin on brain dead organ donors. 15 brain dead organ donors were divided into 2 groups, insulin treated (n=6) and controls (n=9). Insulin was provided for a minimum of 6 h using the hyperinsulinemic normoglycemic clamp technique. The changes of serum cytokines, including IL-6, IL-10, IL-1β, IL-8, TNFα, TGFα and MCP-1, were measured by suspension bead array immunoassay and glucose by a glucose monitor. Compared to controls, insulin treated donors had a significant lower blood glucose 4.8 (4-6.9) vs. 9 (5.6-11.7) mmol/L, pinsulin treated donors compared with those in controls. High dose insulin therapy decreases the concentrations of inflammatory cytokines in brain dead donors and preserves normoglycemia. High dose of insulin may have anti-inflammatory effects in brain dead organ donors and therefore, improve the quality of donor organs and potentially improve outcomes. © Georg Thieme Verlag KG Stuttgart · New York.

Laparoscopic Adjustable Gastric Banding and Hypoglycemia

Directory of Open Access Journals (Sweden)

Sigrid Bairdain

2013-01-01

Full Text Available Obesity is commonplace, and surgical treatment usually includes Roux-en-Y gastric bypasses (RYGBs. RYGBs have the most documented side effects including vitamin deficiencies, rebound weight gain, and symptomatic hypoglycemia; fewer series exist describing hypoglycemia following other bariatric operations. We reviewed all patients undergoing laparoscopic adjustable gastric banding (LAGB at our institution between 2008 and 2012. Three patients were identified to have symptomatic hypoglycemia following LAGB. Mean time from surgery was 33 months (range 14–45 months, and mean weight loss was 32.7 kg (range 15.9–43.1 kg. None of the patients had preexisting diabetes. Therefore, symptomatic hypoglycemia should be investigated irrespective of bariatric operation.

Hypoglycemia, chronic kidney disease, and diabetes mellitus.

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Alsahli, Mazen; Gerich, John E

2014-11-01

Hypoglycemia is a major problem associated with substantial morbidity and mortality in patients with diabetes and is often a major barrier to achieving optimal glycemic control. Chronic kidney disease not only is an independent risk factor for hypoglycemia but also augments the risk of hypoglycemia that is already present in people with diabetes. This article summarizes our current knowledge of the epidemiology, pathogenesis, and morbidity of hypoglycemia in patients with diabetes and chronic kidney disease and reviews therapeutic considerations in this situation. PubMed and MEDLINE were searched for literature published in English from January 1989 to May 2014 for diabetes mellitus, hypoglycemia, chronic kidney disease, and chronic renal insufficiency. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Incidence of hypoglycemia in newborns at risk and an audit of the 2011 American academy of pediatrics guideline for hypoglycemia.

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Hosagasi, Nihan Hilal; Aydin, Mustafa; Zenciroglu, Aysegul; Ustun, Nuran; Beken, Serdar

2017-11-15

Hypoglycemia is low blood glucose level that may negatively affect neurological and developmental prognosis. The American Academy of Pediatrics (AAP), Committee on Fetus and Newborn defined the safe glucose concentrations in the 2011 guideline for newborns at risk for hypoglycemia. This study aimed to investigate the incidence and associated risk factors for hypoglycemia in newborn infants having risk and to assess compliance with the AAP guideline. According to 2011 AAP guideline for hypoglycemia, the newborns at risk for hypoglycemia included in this study were divided to four groups [infant of diabetic mother (IDM), large-for-gestational-age (LGA) infants, small-for-gestational-age (SGA) infants, and late preterm infants (LPI)]. Of the 207 newborn infants, there were 12 cases in IDM group (5.7%), 79 cases in LGA group (38.1%), 66 cases in SGA group (31.8%) and 50 cases in LPI group (24.1%). The incidences of hypoglycemia in these four groups were 2 (16.6%), 10 (12.7%), 8 (12.2%) and 17 (34%), respectively. Although the gender, delivery method, birth weight and 5-min Apgar score at 5-min were not found to be associated with hypoglycemia (P > 0.05), lower gestational age was determined to be associated with higher incidence of hypoglycemia (P = 0.02). Median first feeding time was 55 min and time between first nutrition and blood glucose measurement was 30 min in all cases. Highest risk for hypoglycemia in early postnatal period was present especially in LPI group. Our compliance levels with the AAP guideline was found to be satisfactory. Copyright © 2017. Published by Elsevier B.V.

Intraoperative tight glucose control using hyperinsulinemic normoglycemia increases delirium after cardiac surgery.

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Saager, Leif; Duncan, Andra E; Yared, Jean-Pierre; Hesler, Brian D; You, Jing; Deogaonkar, Anupa; Sessler, Daniel I; Kurz, Andrea

2015-06-01

Postoperative delirium is common in patients recovering from cardiac surgery. Tight glucose control has been shown to reduce mortality and morbidity. Therefore, the authors sought to determine the effect of tight intraoperative glucose control using a hyperinsulinemic-normoglycemic clamp approach on postoperative delirium in patients undergoing cardiac surgery. The authors enrolled 198 adult patients having cardiac surgery in this randomized, double-blind, single-center trial. Patients were randomly assigned to either tight intraoperative glucose control with a hyperinsulinemic-normoglycemic clamp (target blood glucose, 80 to 110 mg/dl) or standard therapy (conventional insulin administration with blood glucose target, battery. The authors considered patients to have experienced postoperative delirium when Confusion Assessment Method testing was positive at any assessment. A positive Confusion Assessment Method was defined by the presence of features 1 (acute onset and fluctuating course) and 2 (inattention) and either 3 (disorganized thinking) or 4 (altered consciousness). Patients randomized to tight glucose control were more likely to be diagnosed as being delirious than those assigned to routine glucose control (26 of 93 vs. 15 of 105; relative risk, 1.89; 95% CI, 1.06 to 3.37; P = 0.03), after adjusting for preoperative usage of calcium channel blocker and American Society of Anesthesiologist physical status. Delirium severity, among patients with delirium, was comparable with each glucose management strategy. Intraoperative hyperinsulinemic-normoglycemia augments the risk of delirium after cardiac surgery, but not its severity.

Association of Hypoglycemia With Subsequent Dementia in Older Patients With Type 2 Diabetes Mellitus.

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Mehta, Hemalkumar B; Mehta, Vinay; Goodwin, James S

2017-08-01

Studies have found conflicting evidence regarding the association of hypoglycemia with dementia. We evaluated an association of hypoglycemia with subsequent dementia in patients with type 2 diabetes. This retrospective longitudinal cohort study used the Clinical Practice Research Datalink, an electronic medical records data from the United Kingdom, from 2003 to 2012. We included patients aged >65 years diagnosed with type 2 diabetes, with no prior diagnosis of dementia. Dementia was defined using diagnosis codes from medical records. All patients were followed from the date of initial diabetes diagnosis. To account for competing risk of death, we used Fine and Gray's competing risk model to determine the association of hypoglycemia with dementia while adjusting for potential confounders. Hypoglycemia was modeled as a time-dependent covariate. Of 53,055 patients, 5.7% (n = 3,018) had at least one hypoglycemia episodes. The overall incidence rate of dementia was 12.7 per 1,000 person-years. In the fully adjusted model that controlled for all confounders, the occurrence of at least one hypoglycemia episode was associated with 27% higher odds of subsequent dementia (hazard ratio = 1.27; 95% confidence interval = 1.06-1.51). The risk increased with the number of hypoglycemia episodes: one episode (hazard ratio = 1.26; 95% confidence interval = 1.03-1.54); two or more episodes (hazard ratio = 1.50; 95% confidence interval = 1.09-2.08). Hypoglycemia is associated with a higher risk of dementia and may be responsible in part for the higher risk of dementia in patients with diabetes. Alternatively, hypoglycemia may be a marker for undiagnosed cognitive impairment, and we cannot rule out the possibility of reverse causation between hypoglycemia and dementia. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Impact of Hypoglycemia on Brain Metabolism During Diabetes.

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Rehni, Ashish K; Dave, Kunjan R

2018-04-10

Diabetes is a metabolic disease afflicting millions of people worldwide. A substantial fraction of world's total healthcare expenditure is spent on treating diabetes. Hypoglycemia is a serious consequence of anti-diabetic drug therapy, because it induces metabolic alterations in the brain. Metabolic alterations are one of the central mechanisms mediating hypoglycemia-related functional changes in the brain. Acute, chronic, and/or recurrent hypoglycemia modulate multiple metabolic pathways, and exposure to hypoglycemia increases consumption of alternate respiratory substrates such as ketone bodies, glycogen, and monocarboxylates in the brain. The aim of this review is to discuss hypoglycemia-induced metabolic alterations in the brain in glucose counterregulation, uptake, utilization and metabolism, cellular respiration, amino acid and lipid metabolism, and the significance of other sources of energy. The present review summarizes information on hypoglycemia-induced metabolic changes in the brain of diabetic and non-diabetic subjects and the manner in which they may affect brain function.

The versatility of the transumbilical approach for laparotomy in infants

African Journals Online (AJOL)

neonates and infants with gastrointestinal surgical ... surgical procedures in neonates and infants. .... trauma to the rectus abdominis muscle, which can cause .... pancreatectomy for persistent hyperinsulinemic hypoglycemia of infancy.

Screening for Hypoglycemia in Exclusively Breastfed High-risk Neonates.

Science.gov (United States)

Singh, Princy; Upadhyay, Amit; Sreenivas, Vishnubhatla; Jaiswal, Vijay; Saxena, Pranjali

2017-06-15

To determine incidence of hypoglycemia in exclusively breastfed, high-risk but healthy newborns, and risk factors for its development. This observational study enrolled 407 exclusively breastfed high-risk (low birth weight newborns (1800-2499 g), late preterms, small-for-gestation, large-for-gestation and infant of diabetic mother), who did not require admission to neonatal intensive care unit and were kept in postnatal wards with mother. Hypoglycemia was defined as blood glucose £46 mg/dL (2.6 mmol/L). Blood glucose was monitored till 48 hours of life. 27% of the screened newborns developed hypoglycemia in first 48 hours. 31 (7.6%) developed recurrent (>2) episodes, 28 (6.8%) had moderate (<37mg/dL) while 8 (1.9%) developed symptomatic hypoglycemia. With increase in birthweight, risk of hypoglycemia reduced significantly (P=0.003). Hypoglycemia was observed more frequently in first 2 hours as compared to next 48 hours (P=0.0001). Low birth- weight, preterm gestation and male gender was significantly associated with increased risk of hypoglycemia. Healthy, high-risk exclusively breastfed newborns in postnatal wards need close monitoring for hypoglycemia in first 24 hrs of life.

Hypoglycemia-associated electroencephalogram and electrocardiogram changes appear simultaneously

DEFF Research Database (Denmark)

Larsen, Anine Poulsen; Højlund, Kurt; Poulsen, Mikael Kjær

2013-01-01

Tight glycemic control in type 1 diabetes mellitus (T1DM) may be accomplished only if severe hypoglycemia can be prevented. Biosensor alarms based on the body's reactions to hypoglycemia have been suggested. In the present study, we analyzed three lead electrocardiogram (ECG) and single-channel e......Tight glycemic control in type 1 diabetes mellitus (T1DM) may be accomplished only if severe hypoglycemia can be prevented. Biosensor alarms based on the body's reactions to hypoglycemia have been suggested. In the present study, we analyzed three lead electrocardiogram (ECG) and single...

Genetics Home Reference: permanent neonatal diabetes mellitus

Science.gov (United States)

... AL. Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia. Hum Mutat. 2009 Nov;30(11):1512-26. ...

β1-Adrenergic receptor deficiency in ghrelin-expressing cells causes hypoglycemia in susceptible individuals

Science.gov (United States)

Mani, Bharath K.; Osborne-Lawrence, Sherri; Vijayaraghavan, Prasanna; Hepler, Chelsea; Zigman, Jeffrey M.

2016-01-01

Ghrelin is an orexigenic gastric peptide hormone secreted when caloric intake is limited. Ghrelin also regulates blood glucose, as emphasized by the hypoglycemia that is induced by caloric restriction in mouse models of deficient ghrelin signaling. Here, we hypothesized that activation of β1-adrenergic receptors (β1ARs) localized to ghrelin cells is required for caloric restriction–associated ghrelin release and the ensuing protective glucoregulatory response. In mice lacking the β1AR specifically in ghrelin-expressing cells, ghrelin secretion was markedly blunted, resulting in profound hypoglycemia and prevalent mortality upon severe caloric restriction. Replacement of ghrelin blocked the effects of caloric restriction in β1AR-deficient mice. We also determined that treating calorically restricted juvenile WT mice with beta blockers led to reduced plasma ghrelin and hypoglycemia, the latter of which is similar to the life-threatening, fasting-induced hypoglycemia observed in infants treated with beta blockers. These findings highlight the critical functions of ghrelin in preventing hypoglycemia and promoting survival during severe caloric restriction and the requirement for ghrelin cell–expressed β1ARs in these processes. Moreover, these results indicate a potential role for ghrelin in mediating beta blocker–associated hypoglycemia in susceptible individuals, such as young children. PMID:27548523

Nondiabetic Hypoglycemia

Science.gov (United States)

... hypoglycemia, which may be related to a disease Glucose is the main source of energy for your body and brain. It comes from what we eat and drink. Insulin, a hormone, helps keep blood glucose at normal levels so your body can work ...

Update on neonatal hypoglycemia.

Science.gov (United States)

Rozance, Paul J

2014-02-01

Neonatal hypoglycemia is one of the most common biochemical abnormalities encountered in the newborn. However, controversy remains surrounding its definition and management especially in asymptomatic patients. New information has been published that describes the incidence and timing of low glucose concentrations in the groups most at risk for asymptomatic neonatal hypoglycemia. Furthermore, one large prospective study failed to find an association between repetitive low glucose concentrations and poor neurodevelopmental outcomes in preterm infants. But hypoglycemia due to hyperinsulinism, especially genetic causes, continued to be associated with brain injury. New advances were made in the diagnosis and management of hyperinsulinism, including acquired hyperinsulinism in small for gestational age infants and others. Continuous glucose monitoring remains an attractive strategy for future research in this area. The fundamental question of how best to manage asymptomatic newborns with low glucose concentrations remains unanswered. Balancing the risks of overtreating newborns with low glucose concentrations who are undergoing a normal transition following birth against the risks of undertreating those in whom low glucose concentrations are pathological, dangerous, and/or a harbinger of serious metabolic disease remains a challenge.

Retrospective evaluation of a national guideline to prevent neonatal hypoglycemia.

Science.gov (United States)

Rasmussen, Annett Helleskov; Wehberg, Sonja; Fenger-Groen, Jesper; Christesen, Henrik Thybo

2017-10-01

Hypoglycemia is common in neonates and may cause adverse neurological outcomes. Guidelines should aim to prevent repeated hypoglycemic episodes in risk groups, but they are not usually stratified according to the severity of hypoglycemia risk, which may lead to inappropriate and redundant interventions. We evaluated the effect of a national prevention guideline stratified according to mild, moderate, and severe risks of hypoglycemia. From national registers, a population cohort of 22,725 neonates was identified retrospectively before and after implementation of a national guideline. Of these, 1900 had World Health Organization International Classification of Diseases 10 discharge diagnoses of hypoglycemia. Diagnoses indicating hypoglycemia risk [small/large for gestational age (SGA/LGA), asphyxia, prematurity, maternal insulin-treated diabetes mellitus] were recorded. Neonatal ward files were evaluated to validate hypoglycemia diagnoses. Adjusted odds ratios (aORs) were calculated, adjusting for sex, parity, SGA, LGA, preterm birth, and asphyxia, where relevant. Primiparity and male sex were associated independently with hypoglycemia diagnosis [aORs, 1.29 (1.17-1.42) and 1.14 (1.03-1.26), respectively]. Overall incidence of hypoglycemia at discharge decreased from 9.4% to 5.5% after guideline implementation [aOR change , 0.57 (0.50-0.64)]. Overall incidence of validated hypoglycemia decreased from 2.1% to 1.2% [aOR 0.59 (0.46-0.77), phypoglycemia incidence decreased from 30.5% to 18.6% [aOR 0.52 (0.36-0.75)] among SGA neonates, from 25.8% to 16.4% [aOR 0.57 (0.42-0.76)] among preterm infants, and from 27.4% to 16.6% [aOR 0.63 (0.34-0.83)] among those with asphyxia. LGA neonates showed a decreased incidence in obstetric wards only. No significant change was observed for the diabetes group. Stratification of hypoglycemia risk in a hypoglycemia prevention guideline was followed by decreased estimated hypoglycemia incidence, but no causative conclusion could be drawn

The impact of severe hypoglycemia and impaired awareness of hypoglycemia on relatives of patients with type 1 diabetes

DEFF Research Database (Denmark)

Jørgensen, Hanne V; Pedersen-Bjergaard, Ulrik; Rasmussen, Ase K

2003-01-01

.01). CONCLUSIONS: Cohabitants of patients with type 1 diabetes recall significantly more episodes of severe hypoglycemia than the patients. The rate of severe hypoglycemia and state of hypoglycemic awareness are the principal determinants of degree of cohabitants' involvement in their partners' disease....

QT measurement and heart rate correction during hypoglycemia

DEFF Research Database (Denmark)

Christensen, Toke Folke; Randløv, Jette; Christensen, Leif Engmann

2010-01-01

induced by intravenous injection of two insulin types in a cross-over design. QT measurements were done using the slope-intersect (SI) and manual annotation (MA) methods. Heart rate correction was done using Bazett's (QTcB) and Fridericia's (QTcF) formulas. Results. The SI method showed significant......Introduction. Several studies show that hypoglycemia causes QT interval prolongation. The aim of this study was to investigate the effect of QT measurement methodology, heart rate correction, and insulin types during hypoglycemia. Methods. Ten adult subjects with type 1 diabetes had hypoglycemia...... prolongation at hypoglycemia for QTcB (42(6) ms; P measuring the QT interval has...

Gut microbiome response to short-term dietary interventions in reactive hypoglycemia subjects.

Science.gov (United States)

Quercia, Sara; Turroni, Silvia; Fiori, Jessica; Soverini, Matteo; Rampelli, Simone; Biagi, Elena; Castagnetti, Andrea; Consolandi, Clarissa; Severgnini, Marco; Pianesi, Mario; Fallucca, Francesco; Pozzilli, Paolo; Brigidi, Patrizia; Candela, Marco

2017-11-01

Reactive hypoglycemia is a metabolic disorder that provokes severe hypoglycemic episodes after meals. Over recent years, the gut microbiota has been recognized as potential target for the control of metabolic diseases, and the possibility to correct gut microbiota dysbioses through diet, favouring the recovery of metabolic homeostasis, has been considered. We investigate the impact of 2 short-term (3-day) nutritional interventions, based on the macrobiotic Ma-Pi 2 diet and a control Mediterranean diet, on the structure and functionality of the gut microbiota in 12 patients affected by reactive hypoglycemia. The gut microbiota composition was characterized by next-generation sequencing of the V3 to V4 region of the 16S rRNA gene, and the ecosystem functionality was addressed by measuring the faecal concentration of short-chain fatty acids (SCFAs). In order to measure the short-term physiological gut microbiota fluctuation, the microbiomes of 7 healthy people were characterized before and after 3 days of constant diet. While no convergence of the gut microbiota compositional profiles was observed, a significant increase in SCFA faecal levels was induced only in the Ma-Pi 2 diet group, suggesting the potential of this diet to support a short-term functional convergence of the gut microbiota, regardless of the individual compositional layout. The Ma-Pi 2 diet, with its high fibre load, was effective in increasing the production of SCFAs by the gut microbiota. Because these metabolites are known for their ability to counterbalance the metabolic deregulation in persons with glucose impairment disorders, their increased bioavailability could be of some relevance in reactive hypoglycemia. Copyright © 2017 John Wiley & Sons, Ltd.

[Uncommon neonatal case of hypoglycemia: ACTH resistance syndrome].

Science.gov (United States)

Delmas, O; Marrec, C; Caietta, E; Simonin, G; Morel, Y; Girard, N; Roucher, F; Sarles, J; Chabrol, B; Reynaud, R

2014-12-01

Monitoring of blood glucose is usually reported to reduce the risk of hypoglycemia in term newborns with high risk factors and for prematurity in neonatal intensive care unit patients. Differential diagnosis has rarely been discussed. In the eutrophic term newborn, hypoglycemia remains rare and an etiological diagnosis must be made. Intensive management of neonatal hypoglycemia is required to prevent neurodevelopmental defects. Without evident cause or if hypoglycemia persists, a systematic review of possible causes should be made. We report isolated glucocorticoid deficiency diagnosed in an infant at 10 months of age. This boy had neonatal hypoglycemia and mild jaundice that had not been investigated. During his first 9 months of life, he presented frequent infections. At 10 months of age, febrile seizures occurred associated with shock, hypoglycemia, hyponatremia, mild hyperpigmentation, and coma. He was diagnosed with hypocortisolemia and elevated ACTH levels. Brain injury was revealed by MRI after resuscitation, with hypoxic-ischemic and hypoglycemic encephalopathy. The molecular studies demonstrated the presence of p.Asp107Asn and previously unreported frameshift p.Pro281GlnfsX9 MC2R gene mutations. A substitutive hormone therapy was provided and during a follow-up of 12 months no adrenal crisis was noted. We report an unusual case of familial glucocorticoid deficiency with severe neurological injury. This case demonstrates the importance of an appropriate etiological diagnosis in neonatal hypoglycemia. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Early feeding and neonatal hypoglycemia in infants of diabetic mothers

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Leandro Cordero

2013-12-01

Full Text Available Objectives: To examine the effects of early formula feeding or breast-feeding on hypoglycemia in infants born to 303 A1-A2 and 88 Class B-RF diabetics. Methods: Infants with hypoglycemia (blood glucose < 40 mg/dL were breast-fed or formula-fed, and those with recurrences were given intravenous dextrose. Results: Of 293 infants admitted to the well-baby nursery, 87 (30% had hypoglycemia, corrected by early feeding in 75 (86%, while 12 (14% required intravenous dextrose. In all, 98 infants were admitted to the newborn intensive care unit for respiratory distress (40%, prematurity (33% or prevention of hypoglycemia (27%. Although all newborn intensive care unit patients received intravenous dextrose, 22 (22% had hypoglycemia. Of 109 hypoglycemia episodes, 89 (82% were single low occurrences. At discharge, 56% of well-baby nursery and 43% of newborn intensive care unit infants initiated breast-feeding. Conclusions: Hypoglycemia among infants of diabetic mothers can be corrected by early breast-feeding or formula feeding.

Early feeding and neonatal hypoglycemia in infants of diabetic mothers

Science.gov (United States)

Ramesh, Shilpa; Hillier, Kirsty; Giannone, Peter J; Nankervis, Craig A

2013-01-01

Objectives: To examine the effects of early formula feeding or breast-feeding on hypoglycemia in infants born to 303 A1-A2 and 88 Class B-RF diabetics. Methods: Infants with hypoglycemia (blood glucose < 40 mg/dL) were breast-fed or formula-fed, and those with recurrences were given intravenous dextrose. Results: Of 293 infants admitted to the well-baby nursery, 87 (30%) had hypoglycemia, corrected by early feeding in 75 (86%), while 12 (14%) required intravenous dextrose. In all, 98 infants were admitted to the newborn intensive care unit for respiratory distress (40%), prematurity (33%) or prevention of hypoglycemia (27%). Although all newborn intensive care unit patients received intravenous dextrose, 22 (22%) had hypoglycemia. Of 109 hypoglycemia episodes, 89 (82%) were single low occurrences. At discharge, 56% of well-baby nursery and 43% of newborn intensive care unit infants initiated breast-feeding. Conclusions: Hypoglycemia among infants of diabetic mothers can be corrected by early breast-feeding or formula feeding. PMID:26770697

Correlation between measures of hypoglycemia and glycemic improvement in sulfonylurea treated patients with type 2 diabetes in India: Results from the OBSTACLE hypoglycemia study

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S Kalra

2014-01-01

Full Text Available Background: This study aimed to assess correlation between measures of hypoglycemia and glycemic control in patients with type 2 diabetes mellitus (T2DM treated with sulfonylureas. Materials and Methods: T2DM patients being initiated on a sulfonylurea (SU on background of a failing oral antihyperglycemic regimen were followed up for 12 weeks. (HbA1c was measured at baseline and end of follow-up. Hypoglycemia was assessed using Stanford Hypoglycemia Questionnaire at week 12. Results: Of the total 1069 patients enrolled, 950 were considered evaluable. A weak negative correlation was observed between end of follow-up HbA1c values and hypoglycemia score, using both linear regression analysis (correlation coefficient -0.12; P = 0.0002 and negative binomial regression (β slope -0.09; P = 0.0010. A similar correlation was also observed between change in HbA1c from baseline and hypoglycemia score (β slope -0.07; P = 0.0048. Mean HbA1c reduction was lowest (0.65 ± 2.27% in patients not reporting any hypoglycemia and highest (1.28 ± 2.40% in patients with hypoglycemia score greater than median of 2 (P = 0.0031. There was no correlation between hypoglycemia frequency and end of follow-up HbA1c values (P = 0.4111. Conclusion: With addition of SU on a background of a failing oral anti-hyperglycemic regimen, the extent of glycemic control correlates directly with measures of patient reported hypoglycemia.

The economic impact of insulin-related hypoglycemia in Denmark

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Hoskins, Nicki; Tikkanen, Christian Klyver; Pedersen-Bjergaard, Ulrik

2017-01-01

AIMS: To estimate the direct cost of hypoglycemia in insulin-treated adults with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in Denmark. MATERIALS AND METHODS: The Local Impact of Hypoglycemia Tool (LIHT) was used to estimate the costs associated with insulin-related hypoglycemia. Average...

Cross-cultural variation in symptom perception of hypoglycemia

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Sanjay Kalra

2013-01-01

Conclusion: Significant cross-cultural differences related to the symptomatology of hypoglycemia are noted. Indian diabetologists should be aware of the varying presentation of hypoglycemia based on language and ethnic background.

Exercise and deficient carbohydrate storage and intake as causes of hypoglycemia.

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Field, J B

1989-03-01

Exercise is associated with a marked increase in glucose uptake by muscle, which is initially supported by breakdown of hepatic glycogen and subsequently by increased gluconeogenesis. If hepatic glucose production is inadequate, hypoglycemia results. During exercise there is decreased plasma insulin and increased catecholamines, glucagon, cortisol, and growth hormone, which contribute to but are not essential for the increased hepatic output of glucose. Although insulin concentrations fall, insulin sensitivity is increased. However, the augmented glucose uptake by muscle is due to other factors. The symptoms of exhaustion during exercise are not due to hypoglycemia, and prevention of hypoglycemia may not prolong the time of exercise to exhaustion. During severe caloric restriction, hepatic glucose production decreases and free fatty acids and ketone bodies become important sources of calories. Although under these circumstances hepatic gluconeogenesis is usually sufficient to prevent hypoglycemia, with very severe caloric restriction hypoglycemia can result. With starvation, insulin concentrations fall while growth hormone and glucagon increase. Frequently the usual symptoms of hypoglycemia are absent in individuals with hypoglycemia from severe caloric restriction. Hypoglycemia from severe caloric restriction has not been totally restricted to underdeveloped areas of the world. In such patients no endocrine abnormalities have been found, and hypoglycemia has persisted despite administration of large amounts of carbohydrate. Pregnancy and lactation could predispose to hypoglycemia in the face of inadequate caloric intake.

Factors associated with hypoglycemia episodes in hospitalized type ...

African Journals Online (AJOL)

during hospital stay were those admitted due to other causes but subsequently developed hypoglycemia ..... Table 3: Association between causes and severity of hypoglycemia episodes .... An animal study in ... American Diabetes Association.

Relationship Between β-cell Response and Insulin Sensitivity in Horses based on the Oral Sugar Test and the Euglycemic Hyperinsulinemic Clamp.

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Lindåse, S; Nostell, K; Söder, J; Bröjer, J

2017-09-01

A hyperbolic relationship between β-cell response and insulin sensitivity (IS) has been described in several species including rodents, dogs, and humans. This relationship has not been elucidated in the horse. To determine whether the hyperbolic relationship between β-cell response and IS exists in horses by using indices of β-cell response from the oral sugar test (OST) and IS measurements from the euglycemic hyperinsulinemic clamp (EHC). A second aim was to compare how well IS estimates from the OST and EHC correlate. Forty-nine horses with different degrees of insulin regulation (normal-to-severe insulin dysregulation). Cross-sectional study. Horses were examined with an OST and an EHC. Decreased IS was associated with increased β-cell response in the horses. Nine of 12 comparisons between indices of β-cell response and IS measures fulfilled the criteria for a hyperbolic relationship. Indices of IS calculated from the OST correlated highly with the insulin-dependent glucose disposal rate (M) and the insulin-dependent glucose disposal rate per unit of insulin (M/I) determined from the EHC (r = 0.81-0.87). A hyperbolic relationship between β-cell response and IS exists in horses, which suggest that horses with insulin dysregulation respond not only with postprandial hyperinsulinemia but are also insulin resistant. The OST is primarily a test for β-cell response rather than a test for IS, but calculated indices of IS from the OST may be useful to estimate IS in horses, especially when the horse is insulin resistant. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Zinc release contributes to hypoglycemia-induced neuronal death.

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Suh, Sang Won; Garnier, Philippe; Aoyama, Koji; Chen, Yongmei; Swanson, Raymond A

2004-08-01

Neurons exposed to zinc exhibit activation of poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme that normally participates in DNA repair but promotes cell death when extensively activated. Endogenous, vesicular zinc in brain is released to the extracellular space under conditions causing neuronal depolarization. Here, we used a rat model of insulin-induced hypoglycemia to assess the role of zinc release in PARP-1 activation and neuronal death after severe hypoglycemia. Zinc staining with N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) showed depletion of presynaptic vesicular zinc from hippocampal mossy fiber terminals and accumulation of weakly bound zinc in hippocampal CA1 cell bodies after severe hypoglycemia. Intracerebroventricular injection of the zinc chelator calcium ethylene-diamine tetraacetic acid (CaEDTA) blocked the zinc accumulation and significantly reduced hypoglycemia-induced neuronal death. CaEDTA also attenuated the accumulation of poly(ADP-ribose), the enzymatic product of PARP-1, in hippocampal neurons. These results suggest that zinc translocation is an intermediary step linking hypoglycemia to PARP-1 activation and neuronal death.

Recurrent Hypoglycemia in a Hemodialysis Patient Related to Propoxyphene Treatment

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Hui-Ting Lee

2007-07-01

Full Text Available There are various etiologies for hypoglycemia in patients with chronic renal failure, and its pathogenesis is complex. Concomitant use of medications is the most common cause. We report a rare case of an 82-year-old woman with type 2 diabetes mellitus in end-stage renal disease undergoing maintenance hemodialysis, who experienced recurrent symptomatic hypoglycemia during treatment with propoxyphene for pain relief. Hypoglycemia occurred simultaneously with elevated levels of serum immunoreactive insulin and C-peptide. After discontinuing propoxyphene, hypoglycemia mitigated and the level of insulin returned to normal range. Our case reminds us that propoxyphene-induced hypoglycemia should not be ignored, especially in hemodialysis patients with cold sweats, agitation and depressed consciousness.

The effect of training on responses of beta-endorphin and other pituitary hormones to insulin-induced hypoglycemia

DEFF Research Database (Denmark)

Mikines, K J; Kjær, Michael; Hagen, C

1985-01-01

in untrained (25 +/- 6 mU X l-1) subjects (P less than 0.05). Levels of thyrotropin (TSH) changed in neither of the groups. It is concluded that, in contrast to what has been formerly proposed, training does not result in a general increase in secretory capacity of the anterior pituitary gland. TSH responds......We studied whether the previously reported intensified beta-endorphin response to exercise after training might result from a training-induced general increase in anterior pituitary secretory capacity. Identical hypoglycemia was induced by insulin infusion in 7 untrained (VO2max 49 +/- 4 ml X (kg X...

What Is Hypoglycemia?

Science.gov (United States)

... symptoms of hypoglycemia are caused when not enough glucose gets to the brain; in fact, the brain is the organ that ... fatigue, and weakness. At its most severe, insufficient glucose flow to the brain can cause confusion, seizures, and loss of consciousness ( ...

Cotrimoxazole-Induced Hypoglycemia in an HIV-Infected Patient

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Christine A Hughes

2001-01-01

Full Text Available A case of cotrimoxazole-induced hypoglycemia is described in a male patient infected with HIV. Ten days after initiating high dose cotrimoxazole for suspected Pneumocystis carinii pneumonia, the patient developed neuroglycopenic symptoms and diaphoresis. Blood glucose levels were repeatedly low, with elevated insulin and C-peptide levels despite multiple intravenous bolus doses and infusions of dextrose. Hypoglycemia resolved after approximately 36 h of treatment with dextrose and discontinuation of cotrimoxazole. A review of reported cases of hypoglycemia associated with cotrimoxazole is provided, including information about onset, risk factors and possible mechanism.

Retrospective Evaluation of a National Guideline to Prevent Neonatal Hypoglycemia

DEFF Research Database (Denmark)

Rasmussen, Annett Helleskov; Wehberg, Sonja; Fenger-Groen, Jesper

2017-01-01

Background: Hypoglycemia is common in neonates and may cause adverse neurological outcomes. Guidelines should aim to prevent repeated hypoglycemic episodes in risk groups, but they are not usually stratified according to the severity of hypoglycemia risk, which may lead to inappropriate...... and redundant interventions. We evaluated the effect of a national prevention guideline stratified according to mild, moderate, and severe risks of hypoglycemia. Methods: From national registers, a population cohort of 22,725 neonates was identified retrospectively before and after implementation of a national....... Neonatal ward files were evaluated to validate hypoglycemia diagnoses. Adjusted odds ratios (aORs) were calculated, adjusting for sex, parity, SGA, LGA, preterm birth, and asphyxia, where relevant. Results: Primiparity and male sex were associated independently with hypoglycemia diagnosis [aORs, 1.29 (1...

Validation of ICD-9-CM coding algorithm for improved identification of hypoglycemia visits

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Lieberman Rebecca M

2008-04-01

Full Text Available Abstract Background Accurate identification of hypoglycemia cases by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM codes will help to describe epidemiology, monitor trends, and propose interventions for this important complication in patients with diabetes. Prior hypoglycemia studies utilized incomplete search strategies and may be methodologically flawed. We sought to validate a new ICD-9-CM coding algorithm for accurate identification of hypoglycemia visits. Methods This was a multicenter, retrospective cohort study using a structured medical record review at three academic emergency departments from July 1, 2005 to June 30, 2006. We prospectively derived a coding algorithm to identify hypoglycemia visits using ICD-9-CM codes (250.3, 250.8, 251.0, 251.1, 251.2, 270.3, 775.0, 775.6, and 962.3. We confirmed hypoglycemia cases by chart review identified by candidate ICD-9-CM codes during the study period. The case definition for hypoglycemia was documented blood glucose 3.9 mmol/l or emergency physician charted diagnosis of hypoglycemia. We evaluated individual components and calculated the positive predictive value. Results We reviewed 636 charts identified by the candidate ICD-9-CM codes and confirmed 436 (64% cases of hypoglycemia by chart review. Diabetes with other specified manifestations (250.8, often excluded in prior hypoglycemia analyses, identified 83% of hypoglycemia visits, and unspecified hypoglycemia (251.2 identified 13% of hypoglycemia visits. The absence of any predetermined co-diagnosis codes improved the positive predictive value of code 250.8 from 62% to 92%, while excluding only 10 (2% true hypoglycemia visits. Although prior analyses included only the first-listed ICD-9 code, more than one-quarter of identified hypoglycemia visits were outside this primary diagnosis field. Overall, the proposed algorithm had 89% positive predictive value (95% confidence interval, 86–92 for

Persistent neonatal hypoglycemia: Diagnosis and management

OpenAIRE

Marles, Sandra L; Casiro, Oscar G

1998-01-01

Maintenance of plasma glucose depends on a normal endocrine system, functional enzyme levels for glycogenolysis, gluconeogenesis and other processes, and there must be an adequate supply of endogenous fat, glycogen and substrates of gluconeogenesis. Neonatal hypoglycemia should be defined as serum glucose less than 2.2 mmol/L in the first 72 h of life and less than 2.5 mmol/L thereafter. The purpose of this paper is to review the more uncommon causes of hypoglycemia in the full term, apparent...

Cost Analysis of Treating Neonatal Hypoglycemia with Dextrose Gel.

Science.gov (United States)

Glasgow, Matthew J; Harding, Jane E; Edlin, Richard

2018-04-03

To evaluate the costs of using dextrose gel as a primary treatment for neonatal hypoglycemia in the first 48 hours after birth compared with standard care. We used a decision tree to model overall costs, including those specific to hypoglycemia monitoring and treatment and those related to the infant's length of stay in the postnatal ward or neonatal intensive care unit, comparing the use of dextrose gel for treatment of neonatal hypoglycemia with placebo, using data from the Sugar Babies randomized trial. Sensitivity analyses assessed the impact of dextrose gel cost, neonatal intensive care cost, cesarean delivery rate, and costs of glucose monitoring. In the primary analysis, treating neonatal hypoglycemia using dextrose gel had an overall cost of NZ$6863.81 and standard care (placebo) cost NZ$8178.25; a saving of NZ$1314.44 per infant treated. Sensitivity analyses showed that dextrose gel remained cost saving with wide variations in dextrose gel costs, neonatal intensive care unit costs, cesarean delivery rates, and costs of monitoring. Use of buccal dextrose gel reduces hospital costs for management of neonatal hypoglycemia. Because it is also noninvasive, well tolerated, safe, and associated with improved breastfeeding, buccal dextrose gel should be routinely used for initial treatment of neonatal hypoglycemia. Australian New Zealand Clinical Trials Registry: ACTRN12608000623392. Copyright © 2018 Elsevier Inc. All rights reserved.

Influence of erythropoietin on cognitive performance during experimental hypoglycemia in patients with type 1 diabetes mellitus: a randomized cross-over trial.

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Peter Lommer Kristensen

Full Text Available The incidence of severe hypoglycemia in type 1 diabetes has not decreased over the past decades. New treatment modalities minimizing the risk of hypoglycemic episodes and attenuating hypoglycemic cognitive dysfunction are needed. We studied if treatment with the neuroprotective hormone erythropoietin (EPO enhances cognitive function during hypoglycemia.Eleven patients with type 1 diabetes, hypoglycemia unawareness and recurrent severe hypoglycemia completed the study. In a double-blind, randomized, balanced, cross-over study using clamped hypoglycemia they were treated with 40,000 IU of EPO or placebo administered intravenously six days before the two experiments. Cognitive function (primary endpoint, hypoglycemic symptoms, and counter-regulatory hormonal response were recorded.Compared with placebo, EPO treatment was associated with a significant reduction in errors in the most complex reaction time task (-4.7 (-8.1 to -1.3, p = 0.01 and a less reaction time prolongation (-66 (-117 to -16 msec, p = 0.02. EPO treatment did not change performance in other measures of cognition. Hypoglycemic symptoms, EEG-changes, and counter-regulatory hormone concentrations did not differ between EPO and placebo treatment.In patients with type 1 diabetes and hypoglycemia unawareness, treatment with EPO is associated with a beneficial effect on cognitive function in a complex reaction time task assessing sustained attention/working memory. Hypoglycemic symptoms and hormonal responses were not changed by EPO treatment.ClinicalTrials.gov NCT00615368.

Effects of Hypoglycemia on Circulating Stem and Progenitor Cells in Diabetic Patients.

Science.gov (United States)

Fadini, Gian Paolo; Boscari, Federico; Cappellari, Roberta; Galasso, Silvia; Rigato, Mauro; Bonora, Benedetta Maria; D'Anna, Marianna; Bruttomesso, Daniela; Avogaro, Angelo

2018-03-01

Iatrogenic hypoglycemia is the most common acute diabetic complication, and it significantly increases morbidity. In people with diabetes, reduction in the levels of circulating stem and progenitor cells predicts adverse outcomes. To evaluate whether hypoglycemia in diabetes affects circulating stem cells and endothelial progenitor cells (EPCs). We performed an experimental hypoglycemia study (Study 1) and a case-control study (Study 2). Tertiary referral inpatient clinic. Type 1 diabetic patients (Study 1, n = 19); diabetic patients hospitalized for severe iatrogenic hypoglycemia, matched inpatient and outpatient controls (Study 2, n = 22/group). Type 1 diabetic patients underwent two in-hospital sessions of glucose monitoring during a breakfast meal with or without induction of hypoglycemia in random order. In Study 2, patients hospitalized for hypoglycemia and matched controls were compared. Circulating stem cells and EPCs were measured by flow cytometry based on the expression of CD34 and kinase insert domain receptor (KDR). In Study 1, the physiologic decline of CD34+KDR+ EPCs from 8 am to 2 pm was abolished by insulin-induced hypoglycemia in type 1 diabetic patients. In Study 2, diabetic patients hospitalized for severe iatrogenic hypoglycemia had significantly lower levels of CD34+ stem cells and CD34+KDR+ EPCs compared with diabetic inpatients or outpatient controls. In diabetic patients, a single mild hypoglycemic episode can compromise the physiologic EPC fluctuation, whereas severe hypoglycemia is associated with a marked reduction in stem cells and EPCs. These data provide a possible link between hypoglycemia and adverse outcomes of diabetes.

Prevalence and underlying etiologies of neonatal hypoglycemia.

Science.gov (United States)

Najati, N; Saboktakin, L

2010-08-01

This study aims at determining the prevalence of neonatal hypoglycemia and its underlying causes. In this prospective study 14168 newborns delivered in Tabriz Alzahra Hospital during 2 years were evaluated in regard to blood glucose level at first 24 h of life. Glucose oxidase method with 4-aminophenazone with a Greiner G-300 was the used method for determining the blood glucose level. Cases with blood glucose causes of this condition, as well as the short-term mortality rate were determined. Prevalence of neonatal hypoglycemia was 0.4% (52 newborns). Underlying causes of hypoglycemia were prematurity (61.5%), diabetic mother (13.6%), septicemia (9.6%), perinatal asphyxia (9.6%), stress (3.8%) and neonatal hyperinsulinism (1.9%). The mortality rate was 53.8%, with prematurity as the leading cause of death.

Cross-cultural variation in symptom perception of hypoglycemia

Science.gov (United States)

Kalra, Sanjay; Balhara, Yatan Pal Singh; Mithal, Ambrish

2013-01-01

Background: Cross-cultural differences in attitudes and practices related to diabetes are well-known. Similar differences in symptom reporting of endocrine conditions such as menopause are well documented. Minimal literature is available on the cross-cultural variation in reporting of hypoglycemic symptoms. Aims: This cross-sectional study aimed to assess the symptoms of hypoglycemia encountered by diabetologists who deal with patients from different language groups from various states of North and West India and Nepal. Materials and Methods: Eighty three doctors from six Indian states and Nepal, attending a continuing medical education program were requested to fill a detailed, pre-tested, Likert scale based questionnaire which assessed the frequency and symptoms with which patients presented with hypoglycemia in their clinical practice. Data were analyzed based on geographic location of the diabetologists and language spoken by their patients (Hindi vs. Gujarati). Results: Gujarati-speaking patients tended to report to their doctors, a greater inability to work under pressure and a higher frequency of intense hunger during hypoglycemia. They were less likely to report specific adrenergic (inward trembling), neuroglycopenic (feeling down over nothing), and nocturnal (crumpled bedsheets upon waking up) symptoms. Conclusion: Significant cross-cultural differences related to the symptomatology of hypoglycemia are noted. Indian diabetologists should be aware of the varying presentation of hypoglycemia based on language and ethnic background. PMID:24672191

Refractory hypoglycemia in a patient with functional adrenal cortical carcinoma

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Katia Regina Marchetti

2016-11-01

Full Text Available Adrenacarcinomas are rare, and hypoglycemic syndrome resulting from the secretion of insulin-like growth factor II (IGF-II by these tumors have been described infrequently. This study describes the case of a young woman with severe persistent hypoglycemia and a large adrenal tumor and discusses the physiopathological mechanisms involved in hypoglycemia. The case is described as a 21-year-old woman who presented with 8 months of general symptoms and, in the preceding 3 months, with episodes of mental confusion and visual blurring secondary to hypoglycemia. A functional assessment of the adrenal cortex revealed ACTH-independent hypercortisolism and hyperandrogenism. Hypoglycemia, hypoinsulinemia, low C-peptide and no ketones were also detected. An evaluation of the GH–IGF axis revealed GH blockade (0.03; reference: up to 4.4 ng/mL, greatly reduced IGF-I levels (9.0 ng/mL; reference: 180–780 ng/mL, slightly reduced IGF-II levels (197 ng/mL; reference: 267–616 ng/mL and an elevated IGF-II/IGF-I ratio (21.9; reference: ~3. CT scan revealed a large expansive mass in the right adrenal gland and pulmonary and liver metastases. During hospitalization, the patient experienced frequent difficult-to-control hypoglycemia and hypokalemia episodes. Octreotide was ineffective in controlling hypoglycemia. Due to unresectability, chemotherapy was tried, but after 3 months, the patient’s condition worsened and progressed to death. In conclusion, our patient presented with a functional adrenal cortical carcinoma, with hyperandrogenism associated with hypoinsulinemic hypoglycemia and blockage of the GH–IGF-I axis. Patient’s data suggested a diagnosis of hypoglycemia induced by an IGF-II or a large IGF-II-producing tumor (low levels of GH, greatly decreased IGF-I, slightly decreased IGF-II and an elevated IGF-II/IGF-I ratio.

Prevention of acute/severe hypoglycemia-induced neuron death by lactate administration.

Science.gov (United States)

Won, Seok Joon; Jang, Bong Geom; Yoo, Byung Hoon; Sohn, Min; Lee, Min Woo; Choi, Bo Young; Kim, Jin Hee; Song, Hong Ki; Suh, Sang Won

2012-06-01

Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who attempt tight control of blood glucose and may lead to cognitive dysfunction. Accumulating evidence from animal models suggests that hypoglycemia-induced neuronal death is not a simple result of glucose deprivation, but is instead the end result of a multifactorial process. In particular, the excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide adenine dinucleotide (NAD(+)), resulting in energy failure. In this study, we investigate whether lactate administration in the absence of cytosolic NAD(+) affords neuroprotection against hypoglycemia-induced neuronal death. Intraperitoneal injection of sodium L-lactate corrected arterial blood pH and blood lactate concentration after hypoglycemia. Lactate administered without glucose was not sufficient to promote electroencephalogram recovery from an isoelectric state during hypoglycemia. However, supplementation of glucose with lactate reduced neuronal death by ∼80% in the hippocampus. Hypoglycemia-induced superoxide production and microglia activation was also substantially reduced by administration of lactate. Taken together, these results suggest an intriguing possibility: that increasing brain lactate following hypoglycemia offsets the decrease in NAD(+) due to overactivation of PARP-1 by acting as an alternative energy substrate that can effectively bypass glycolysis and be fed directly to the citric acid cycle to maintain cellular ATP levels.

Severe Hypoglycemia Accompanied with Thyroid Crisis

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Yuki Nakatani

2012-01-01

Full Text Available We report a 32-year-old Japanese women with severe hypoglycemia accompanied with thyroid crisis. She complained of dyspnea, general fatigue, and leg edema. She was diagnosed with hyperthyroidism with congestive heart failure and liver dysfunction. Soon after admission, sudden cardiopulmonary arrest occurred. She was then transferred to the intensive care unit. Her serum glucose level was 7 mg/dl. Intravenous glucose, hydrocortisone, diuretics, and continuous hemodiafiltration (CHDF saved her. We considered that hypoglycemia occurred due to heart failure and liver dysfunction due to thyroid crisis.

Brain injuries due to neonatal hypoglycemia: case report

International Nuclear Information System (INIS)

Kim, Dae Bong; Song, Chang Joon; Chang, Mae Young; Youn, Hyae Won

2003-01-01

Although hypoglycemia may be common among neonates, brain injuries resulting from isolated neonatal hypoglycemia are rare. The condition may cause neurological symptoms such as stupor, jitteriness, and seizures, though in their absence, diagnosis delayed or difficult. Hypoglycemia was diagnosed in a three-day-old neonate after he visited the emergency department with loose stool, poor oral intake, and decreased activity, first experienced two days earlier. Two days after his visity, several episodes of seizure occurred. T2 and diffusion-weighted magnetic resonance (MR) scanning, performed at 11 days of age, revealed bilateral and symmetrical high signal intensity lesions in occipital, parietal, and temporal lobes. We report the MR findings of hypoglycemic encephalopathy in a neonate

Testicular regulation of neuronal glucose and monocarboxylate transporter gene expression profiles in CNS metabolic sensing sites during acute and recurrent insulin-induced hypoglycemia.

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Vavaiya, Kamlesh V; Paranjape, Sachin A; Briski, Karen P

2007-01-01

Recurrent insulin-induced hypoglycemia (RIIH) impairs glucose counter-regulatory function in male humans and rodents and, in the latter, diminishes neuronal activation in CNS structures that monitor metabolic homeostasis, including the lateral hypothalamic area (LHA) and dorsal vagal complex (DVC). We investigated whether habituated neuronal reactivity in CNS sensing sites to hypoglycemia is correlated with modified monocarboxylate and/or glucose uptake by using quantitative real-time RT-PCR to analyze neuronal monocarboxylate transporter (MCT2) and glucose transporter variant (GLUT and GLUT4) gene expression profiles in the microdissected LHA, ventromedial nucleus hypothalamus (VMH), and DVC after one or multiple insulin injections. Because orchidectomy (ORDX) maintains uniform glycemic responses to RIIH in male rats, we also examined whether regional gene response patterns are testes dependent. In the intact male rat DVC, MCT2, GLUT3, and GLUT4 gene expression was not altered by acute hypoglycemia but was enhanced by RIIH. MCT2 and GLUT3 mRNA levels in the ORDX rat DVC did not differ among groups, but GLUT4 transcripts were progressively increased by acute and recurrent hypoglycemia. Precedent hypoglycemia decreased or increased basal MCT2 and GLUT4 gene expression, respectively, in the intact rat LHA; LHA GLUT3 transcription was augmented by RIIH in intact rats only. Acute hypoglycemia suppressed MCT2, GLUT3, and GLUT4 gene expression in the intact rat VMH, a response that was abolished by RIIH. In ORDX rats, VMH gene transcript levels were unchanged in response to one dose of insulin but were selectively diminished during RIIH. These data demonstrate site-specific, testes-dependent effects of acute and recurrent hypoglycemia on neuronal metabolic substrate transporter gene expression in characterized rat brain metabolic sensing loci and emphasize the need to assess the impact of potential alterations in glucose and lactate uptake during RIIH on general and

Evaluation of carbohydrate restriction as primary treatment for post-gastric bypass hypoglycemia.

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van Meijeren, Jorick; Timmer, Ilse; Brandts, Hans; Janssen, Ignace; Boer, Hans de

2017-03-01

Up to 15% of patients who have undergone Roux-en-Y gastric bypass (RYGB) surgery may eventually develop symptoms of hypoglycemia. To evaluate the daily life efficacy of a carbohydrate (carb)-restricted dietary advice (CRD) of 6 meals per day with a 30 g carb maximum per meal in patients with documented post-RYGB hypoglycemia. Teaching hospital, the Netherlands. Frequency and severity of hypoglycemic events before and after CRD were assessed retrospectively in 41 patients with documented post-RYGB hypoglycemia, based on medical records and telephone questionnaires. Hypoglycemia was defined as a blood glucose leveltreatment of hypoglycemia, decreased from 23 to 6 (Pmeals per day with up to 30 g carbs each, is an effective treatment of post-RYGB hypoglycemia in the majority of patients. Additional medication is needed in about a third of patients. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Pyruvate administration reduces recurrent/moderate hypoglycemia-induced cortical neuron death in diabetic rats.

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Bo Young Choi

Full Text Available Recurrent/moderate (R/M hypoglycemia is common in type 1 diabetes patients. Moderate hypoglycemia is not life-threatening, but if experienced recurrently it may present several clinical complications. Activated PARP-1 consumes cytosolic NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1 activation may render cells unable to use glucose even when glucose availability is restored. Pyruvate, however, can be metabolized in the absence of cytosolic NAD. We therefore hypothesized that pyruvate may be able to improve the outcome in diabetic rats subjected to insulin-induced R/M hypoglycemia by terminating hypoglycemia with glucose plus pyruvate, as compared with delivering just glucose alone. In an effort to mimic juvenile type 1 diabetes the experiments were conducted in one-month-old young rats that were rendered diabetic by streptozotocin (STZ, 50mg/kg, i.p. injection. One week after STZ injection, rats were subjected to moderate hypoglycemia by insulin injection (10 U/kg, i.p. without anesthesia for five consecutive days. Pyruvate (500 mg/kg was given by intraperitoneal injection after each R/M hypoglycemia. Three hours after last R/M hypoglycemia, zinc accumulation was evaluated. Three days after R/M hypoglycemia, neuronal death, oxidative stress, microglial activation and GSH concentrations in the cerebral cortex were analyzed. Sparse neuronal death was observed in the cortex. Zinc accumulation, oxidative injury, microglial activation and GSH loss in the cortex after R/M hypoglycemia were all reduced by pyruvate injection. These findings suggest that when delivered alongside glucose, pyruvate may significantly improve the outcome after R/M hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation.

Recurrent hypoglycemia increases anxiety and amygdala norepinephrine release during subsequent hypoglycemia

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Ewan eMcNay

2015-11-01

Full Text Available Recurrent hypoglycemia (RH is a common and debilitating side effect of therapy in patients with both type 1 and, increasingly, type 2 diabetes. Previous studies in rats have shown marked effects of RH on subsequent hippocampal behavioral, metabolic, and synaptic processes. In addition to impaired memory, patients experiencing RH report alterations in cognitive processes that include mood and anxiety, suggesting that RH may also affect amygdala function. We tested the impact of RH on amygdala function using an elevated plus-maze test of anxiety together with in vivo amygdala microdialysis for norepinephrine (NEp, a widely used marker of basolateral amygdala cognitive processes. In contrast to findings in the hippocampus and pre-frontal cortex, neither RH nor acute hypoglycemia alone significantly affected plus-maze performance or NEp release. However, animals tested when hypoglycemic who had previously experienced RH had elevated amygdala NEp during plus-maze testing, accompanied by increased anxiety (i.e. less time spent in the open arms of the plus-maze. The results show that RH has widespread effects on subsequent brain function, which vary by neural system.

Severe hypoglycemia and risks of vascular events and death.

NARCIS (Netherlands)

Zoungas, S.; Patel, A.; Chalmers, J.; Galan, B.E. de; Li, Q.; Billot, L.; Woodward, M.; Ninomiya, T.; Neal, B.; MacMahon, S; Grobbee, D.E.; Kengne, A.P.; Marre, M.; Heller, S.

2010-01-01

BACKGROUND: Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention. We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse

β-Receptor-mediated increase in cerebral blood flow during hypoglycemia

International Nuclear Information System (INIS)

Hollinger, B.R.; Bryan, R.M.

1987-01-01

The authors tested the hypothesis that β-adrenergic receptor stimulation is involved with the increase in regional cerebral blood flow (rCBF) during hypoglycemia. Rats were surgically prepared with the use of halothane-nitrous oxide anesthesia. A plaster restraining cast was placed around the hindquarters, and anesthesia was discontinued. Hypoglycemia was produced by an intravenous injection of insulin; normoglycemic control rates were given saline. Propranolol was administered to some control and some hypoglycemic rats to block the β-adrenergic receptors. Regional CBF was measured using 4-[N-methyl- 14 C]iodoantipyrine. Regional CBF increased during hypoglycemia in rats that were not treated with propranolol. The increase varied from ∼60 to 200% depending on the brain region. During hypoglycemia, propranolol abolished the increase in rCBF in the hypothalamus, cerebellum, and pyramidal tract. In other regions the increase in rCBF was only 33-65% of the increase in hypoglycemic rats that were not treated with propranolol. They conclude that β-receptor stimulation plays a major role in the increase in rCBF during hypoglycemia

Congenital Hypoglycemia Disorders: New Aspects of Etiology, Diagnosis, Treatment and Outcomes: Highlights of the Proceedings of the Congenital Hypoglycemia Disorders Symposium, Philadelphia April 2016.

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De Leon, Diva D; Stanley, Charles A

2017-02-01

Hypoglycemia continues to be an important cause of morbidity in neonates and children. Prompt diagnosis and management of the underlying hypoglycemia disorder is critical for preventing brain damage and improving outcomes. Congenital hyperinsulinism (HI) is the most common and severe cause of persistent hypoglycemia in neonates and children. Recent discoveries of the genetic causes of HI have improved our understanding of the pathophysiology, but its management is complex and requires the integration of clinical, biochemical, molecular, and imaging findings to establish the appropriate treatment according to the subtype. Here we present a summary of a recent international symposium on congenital hypoglycemia disorders with emphasis on novel molecular mechanisms resulting in HI, genetic diagnosis, overall approach to management, novel therapies under development, and current outcomes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neonatal hypoglycemia: prevalence and clinical manifestations in tehran children's hospital

International Nuclear Information System (INIS)

Dashti, N.; Einollahi, N.; Abbasi, S.

2007-01-01

To measure the prevalence of hypoglycemia among newborn infants in Children Hospital using a standard laboratory glucose method and to evaluate the evidence of clinical manifestations of hypoglycemia, designing appropriate strategies for prevention and treatment. The study population consisted of 673 neonates in Tehran Children's Hospital and was conducted between June 2004 and March 2005. The incidence of neonatal hypoglycemia in the present study group was 15.15% live births. The clinical features which remained significantly associated with the hypoglycemic neonates were refusal of feeding (45%), hyporeflexia (36.2%), irritability (30%), cyanosis (28.4%), tackypnea (24.5%), seizure (16.6%), weak cry (15.8%), apneic spels (9.8%), pallor (1.9%), cardiac arrest (9.1%) and sweating (1%). Hypoglycemia does occur frequently in newborn infants and requires careful monitoring and therapy of serum glucose. (author)

Glucose turnover during insulin-induced hypoglycemia in liver-denervated rats

DEFF Research Database (Denmark)

Mikines, K J; Sonne, B; Richter, Erik

1985-01-01

The role of hepatic autonomic nerves in glucose production during hypoglycemia was studied. Selective, surgical denervation of the liver was performed in rats, which reduced hepatic norepinephrine concentrations by 96%. Hypoglycemia was induced by 250 mU of insulin intra-arterially in anesthetized...... as well as in chronically catheterized, awake rats. Half of the anesthetized denervated or sham-operated rats had previously been adrenodemedullated. Glucose turnover was measured by primed, constant intravenous infusion of [3-3H]glucose. Before as well as during hypoglycemia the arterial glucose...

Effect of Insulin Analogs on Frequency of Non-Severe Hypoglycemia in Patients with Type 1 Diabetes Prone to Severe Hypoglycemia

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Agesen, Rikke Mette; Kristensen, Peter Lommer; Beck-Nielsen, Henning

2018-01-01

-monitoring of blood glucose (SMBG) in patients with type 1 diabetes and recurrent severe hypoglycemia. Methods: Fifty-three patients completed a substudy of 4 × 3 days of blinded CGM. CGM traces were reviewed for hypoglycemic events lasting 15 min or longer. Results: At the threshold ≤3.9 mmol/L, the per......Background: Hypoglycemia is an increasingly important endpoint in clinical diabetes trials. The assessment of hypoglycemia should therefore be as complete as possible. Blinded continuous glucose monitoring (CGM) provides an improved opportunity to capture asymptomatic and nocturnal events. Here we...... times shorter using CGM data than SMBG data (1.4 vs. 47 weeks). Conclusions: Capturing hypoglycemic events by the conventional method of SMBG in patients with impaired awareness reveals only a limited number of events. Blinded CGM can provide more complete data, particularly in terms of asymptomatic...

Hypoglycemia evaluation and reporting in diabetes: Importance for the development of new therapies.

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Klonoff, David C; Alexander Fleming, G; Muchmore, Douglas B; Frier, Brian M

2017-07-01

Hypoglycemia complicating diabetes therapy is well recognized to be an ever-present threat to patients, their families, providers, payers, and regulators. Despite this being widely acknowledged, the regulatory stance on hypoglycemia as an endpoint in clinical trials to support new product registration has not evolved in any meaningful way since the publication of a position paper by an American Diabetes Association (ADA) Workgroup in 2005. As the impact of hypoglycemia on persons affected by diabetes is of major importance when assessing new treatments, the historical position of regulatory agencies on hypoglycemia is reviewed with respect to product approvals. The purpose of this article is to present proposals for facilitating development of therapies that reduce hypoglycemia risk through (1) development of composite measures of benefit for regulatory endpoints and (2) facilitation of the fulfillment of an unmet clinical need for reducing hypoglycemia. In view of greater comprehension of the effects of hypoglycemia, coupled with improved methodology to assess its frequency, the authors recommend: (1) a numerical cut point of <54 mg/dl (<3.0 mmol/L) as a clinically relevant level with which to define meaningful hypoglycemia for trials of diabetes therapies; (2) utilization in clinical trials of mature glucose monitoring technologies for purposes of regulatory evaluation and clinical decision-making; and (3) development of primary efficacy endpoint composites that include hypoglycemia rates and glycemic control. Copyright © 2017 John Wiley & Sons, Ltd.

Avoiding hypoglycemia: a key to success for glucose-lowering therapy in type 2 diabetes

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Ahrén B

2013-04-01

Full Text Available Bo Ahrén Department of Clinical Sciences, Lund, Faculty of Medicine, Lund University, Lund, Sweden Abstract: Type 2 diabetes carries a risk for hypoglycemia, particularly in patients on an intensive glucose control plan as a glucose-lowering strategy, where hypoglycemia may be a limitation for the therapy and also a factor underlying clinical inertia. Glucose-lowering medications that increase circulating insulin in a glucose-independent manner, such as insulin and sulfonylurea therapy, are the most common cause of hypoglycemia. However, other factors such as a delayed or missed meal, physical exercise, or drug or alcohol consumption may also contribute. Specific risk factors for development of hypoglycemia are old age, long duration of diabetes, some concomitant medication, renal dysfunction, hypoglycemia unawareness, and cognitive dysfunction. Hypoglycemia is associated with acute short-term symptoms related to either counterregulation, such as tachycardia and sweating, or to neuroglycopenia, such as irritability, confusion, and in severe cases stupor, coma, and even death. However, there are also long-term consequences of hypoglycemia such as reduced working capacity, weight gain, loss of self-confidence with reduced quality of life, and increased risk for cardiovascular diseases. For both the patients, the health care system, and the society at large, hypoglycemia carries a high cost. Strategies to mitigate the risk of hypoglycemia include awareness of the condition; education of patients, relatives, and health-care providers; and selecting appropriate glucose-lowering medication that also judges the risk for hypoglycemia to prevent this complication. This article summarizes the current knowledge of hypoglycemia and its consequences with a special emphasis on its consequences for the choice of glucose-lowering therapy. Keywords: type 2 diabetes, hypoglycemia, treatment, sulfonylurea, incretin therapy, insulin

Heterogeneity in phenotype of usher-congenital hyperinsulinism syndrome: hearing loss, retinitis pigmentosa, and hyperinsulinemic hypoglycemia ranging from severe to mild with conversion to diabetes.

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Al Mutair, Angham N; Brusgaard, Klaus; Bin-Abbas, Bassam; Hussain, Khalid; Felimban, Naila; Al Shaikh, Adnan; Christesen, Henrik T

2013-03-01

To evaluate the phenotype of 15 children with congenital hyperinsulinism (CHI) and profound hearing loss, known as Homozygous 11p15-p14 Deletion syndrome (MIM #606528). Prospective clinical follow-up and genetic analysis by direct sequencing, multiplex ligation-dependent probe amplification, and microsatellite markers. Genetic testing identified the previous described homozygous deletion in 11p15, USH1C:c.(90+592)_ABCC8:c.(2694-528)del. Fourteen patients had severe CHI demanding near-total pancreatectomy. In one patient with mild, transient neonatal hypoglycemia and nonautoimmune diabetes at age 11 years, no additional mutations were found in HNF1A, HNF4A, GCK, INS, and INSR. Retinitis pigmentosa was found in two patients aged 9 and 13 years. No patients had enteropathy or renal tubular defects. Neuromotor development ranged from normal to severe delay with epilepsy. The phenotype of Homozygous 11p15-p14 Deletion syndrome, or Usher-CHI syndrome, includes any severity of neonatal-onset CHI and severe, sensorineural hearing loss. Retinitis pigmentosa and nonautoimmune diabetes may occur in adolescence.

ASPIRE In-Home: rationale, design, and methods of a study to evaluate the safety and efficacy of automatic insulin suspension for nocturnal hypoglycemia.

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Klonoff, David C; Bergenstal, Richard M; Garg, Satish K; Bode, Bruce W; Meredith, Melissa; Slover, Robert H; Ahmann, Andrew; Welsh, John B; Lee, Scott W

2013-07-01

Nocturnal hypoglycemia is a barrier to therapy intensification efforts in diabetes. The Paradigm® Veo™ system may mitigate nocturnal hypoglycemia by automatically suspending insulin when a prespecified sensor glucose threshold is reached. ASPIRE (Automation to Simulate Pancreatic Insulin REsponse) In-Home (NCT01497938) was a multicenter, randomized, parallel, adaptive study of subjects with type 1 diabetes. The control arm used sensor-augmented pump therapy. The treatment arm used sensor-augmented pump therapy with threshold suspend, which automatically suspends the insulin pump in response to a sensor glucose value at or below a prespecified threshold. To be randomized, subjects had to have demonstrated ≥2 episodes of nocturnal hypoglycemia, defined as >20 consecutive minutes of sensor glucose values ≤65 mg/dl starting between 10:00 PM and 8:00 AM in the 2-week run-in phase. The 3-month study phase evaluated safety by comparing changes in glycated hemoglobin (A1C) values and evaluated efficacy by comparing the mean area under the glucose concentration time curves for nocturnal hypoglycemia events in the two groups. Other outcomes included the rate of nocturnal hypoglycemia events and the distribution of sensor glucose values. Data from the ASPIRE In-Home study should provide evidence on the safety of the threshold suspend feature with respect to A1C and its efficacy with respect to severity and duration of nocturnal hypoglycemia when used at home over a 3-month period. © 2013 Diabetes Technology Society.

Hypoglycemia in Older People - A Less Well Recognized Risk Factor for Frailty

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Abdelhafiz, Ahmed H; Rodríguez-Mañas, Leocadio; Morley, John E.; Sinclair, Alan J

2015-01-01

Recurrent hypoglycemia is common in older people with diabetes and is likely to be less recognized and under reported by patients and health care professionals. Hypoglycemia in this age group is associated with significant morbidities leading to both physical and cognitive dysfunction. Repeated hospital admissions due to frequent hypoglycemia are also associated with further deterioration in patients’ general health. This negative impact of hypoglycemia is likely to eventually lead to frailty, disability and poor outcomes. It appears that the relationship between hypoglycemia and frailty is bidirectional and mediated through a series of influences including under nutrition. Therefore, attention should be paid to the management of under nutrition in the general elderly population by improving energy intake and maintaining muscle mass. Increasing physical activity and having a more conservative approach to glycemic targets in frail older people with diabetes may be worthwhile. PMID:25821643

Histopathological nerve and skeletal muscle changes in rats subjected to persistent insulin-induced hypoglycemia

DEFF Research Database (Denmark)

Jensen, Vivi Flou Hjorth; Mølck, Anne-Marie; Heydenreich, Annette

2016-01-01

femoris muscle tissue, as little is known about the response to persistent hypoglycemia in these tissues. Histopathologic changes in insulin-infused animals included axonal degeneration and myofibre degeneration. To our knowledge, this is the first study to show that persistent IIH provokes peripheral...

[Hypoglycemia as a cause of traffic accidents].

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Metter, D

1989-05-01

Hypoglycemia is the most important subsidiary effect of insulin therapy, where traffic medicine is concerned. A study has been made of 8 motor car drivers each dependent on insulin and involved in road accidents. The evidence was issued during the trial. The questions set out to prove if there was a state of hypoglycemia and if the afflicted could have foreseen this condition. In 5 cases the driving conduct before the accidents was evident in cordinatory disturbances, which resulted in sinuous driving. The accidents all happened in every-day traffic conditions, namely counter traffic (3), front-end collision (3) and through disregard of right-of-way at cross-roads (1). A further accident was conditioned by an alcoholic state while parking in a car-park. The disturbances in consciousness conditioned by hypoglycemia occurred without warning. In 3 cases the predictability (in legal terms Actio libera in causa) had to be conceded, because the drivers had set out on their routes despite warning signals or insufficient intake of nourishment beforehand.

Factors associated with nocturnal hypoglycemia in at-risk adolescents and young adults with type 1 diabetes.

Science.gov (United States)

Wilson, Darrell M; Calhoun, Peter M; Maahs, David M; Chase, H Peter; Messer, Laurel; Buckingham, Bruce A; Aye, Tandy; Clinton, Paula K; Hramiak, Irene; Kollman, Craig; Beck, Roy W

2015-06-01

Hypoglycemia remains an impediment to good glycemic control, with nocturnal hypoglycemia being particularly dangerous. Information on major contributors to nocturnal hypoglycemia remains critical for understanding and mitigating risk. Continuous glucose monitoring (CGM) data for 855 nights were studied, generated by 45 subjects 15-45 years of age with hemoglobin A1c (HbA1c) levels of ≤8.0% who participated in a larger randomized study. Factors assessed for potential association with nocturnal hypoglycemia (CGM measurement of <60 mg/dL for ≥30 min) included bedtime blood glucose (BG), exercise intensity, bedtime snack, insulin on board, day of the week, previous daytime hypoglycemia, age, gender, HbA1c level, diabetes duration, daily basal insulin, and daily insulin dose. Hypoglycemia occurred during 221 of 885 (25%) nights and was more frequent with younger age (P<0.001), lower HbA1c levels (P=0.006), medium/high-intensity exercise during the preceding day (P=0.003), and the occurrence of antecedent daytime hypoglycemia (P=0.001). There was a trend for lower bedtime BG levels to be associated with more frequent nocturnal hypoglycemia (P=0.10). Bedtime snack, before bedtime insulin bolus, weekend versus weekday, gender, and daily basal and bolus insulin were not associated with nocturnal hypoglycemia. Awareness that HbA1c level, exercise, bedtime BG level, and daytime hypoglycemia are all modifiable factors associated with nocturnal hypoglycemia may help patients and providers decrease the risk of hypoglycemia at night. Risk for nocturnal hypoglycemia increased in a linear fashion across the range of variables, with no clear-cut thresholds to guide clinicians or patients for any particular night.

Sleep disturbances in IDDM patients with nocturnal hypoglycemia

DEFF Research Database (Denmark)

Bendtson, I; Gade, J; Thomsen, C E

1992-01-01

Eight insulin-dependent diabetic patients were studied to evaluate sleep patterns during normoglycemia and spontaneous and insulin-induced hypoglycemia. Two channels of electroencephalogram (EEG), electromyogram and actooculogram were recorded. The signals were analyzed off-line, using...... a polygraphic sleep analysis system. The scoring was mainly based on the color density spectral array of the EEG. Blood glucose and growth hormone were measured serially. Asymptomatic, spontaneous nocturnal hypoglycemia occurred in 38% of the nights. Conventional sleep analysis showed a tendency toward...

Blood electrolyte disturbances during severe hypoglycemia in Korean patients with type 2 diabetes.

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Kang, Mi Yeon

2015-09-01

To investigate abnormalities in blood electrolyte levels during severe hypoglycemia in Korean patients with type 2 diabetes mellitus (T2DM) in a clinical setting. Blood electrolyte levels in adult T2DM patients during severe hypoglycemia were collected from January 1, 2008 to December 31, 2012. Patients who maintained normal serum creatinine and blood urea nitrogen levels were utilized in the study. Severe hypoglycemia was defined as a condition requiring medical assistance, such as administering carbohydrates when serum glucose levels less than 70 mg/dL were observed, in conjunction with other symptoms of hypoglycemia. A total of 1,068 patients who visited the emergency room with severe hypoglycemia were screened, of which 219 patients were included in this study. The incidence of abnormal levels for any electrolyte was 47%. Hypokalemia (type of electrolyte disturbance observed at 21.9%. A decrease in serum potassium levels was associated with decreases in blood glucose levels (r = 0.151, p = 0.025). During severe hypoglycemia, median blood glucose levels, incidence of tachycardia (> 100 beats per minute) and severe hypertension (≥ 180/120 mmHg) were 30 mg/dL (range, 14 to 62) and 35 mg/dL (range, 10 to 69; p = 0.04), 18.8% and 7.2% (p = 0.02), and 20.8% and 10.2% (p = 0.05) in the hypokalemia and normokalemia groups, respectively. During severe hypoglycemia, hypokalemia occurred in 21.9% of T2DM patients and was associated with tachycardia and severe hypertension. Therefore, the results suggest that severe hypoglycemia may increase cardiovascular events in T2DM.

Ventromedial hypothalamic expression of Bdnf is required to establish normal patterns of afferent GABAergic connectivity and responses to hypoglycemia

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Anna Kamitakahara

2016-02-01

Full Text Available Objective: The ventromedial nucleus of the hypothalamus (VMH controls energy and glucose homeostasis through direct connections to a distributed network of nuclei in the hypothalamus, midbrain, and hindbrain. Structural changes in VMH circuit morphology have the potential to alter VMH function throughout life, however, molecular signals responsible for specifying its neural connections are not fully defined. The VMH contains a high density of neurons that express brain-derived neurotrophic factor (BDNF, a potent neurodevelopmental effector known to regulate neuronal survival, growth, differentiation, and connectivity in a number of neural systems. In the current study, we examined whether BDNF impacts the afferent and efferent connections of the VMH, as well as energy homeostatic function. Methods: To determine if BDNF is required for VMH circuit formation, a transgenic mouse model was used to conditionally delete Bdnf from steroidogenic factor 1 (SF1 expressing neurons of the VMH prior to the onset of establishing neural connections with other regions. Projections of SF1 expressing neurons were visualized with a genetically targeted fluorescent label and immunofluorescence was used to measure the density of afferents to SF1 neurons in the absence of BDNF. Physiological changes in body weight and circulating blood glucose were also evaluated in the mutant mice. Results: Our findings suggest that BDNF is required to establish normal densities of GABAergic afferents onto SF1 neurons located in the ventrolateral part of the VMH. Furthermore, loss of BDNF from VMH SF1 neurons results in impaired physiological responses to insulin-induced hypoglycemia. Conclusion: The results of this study indicate that BDNF is required for formation and/or maintenance of inhibitory inputs to SF1 neurons, with enduring effects on glycemic control. Author Video: Author Video Watch what authors say about their articles Keywords: Ventromedial nucleus of the hypothalamus

Pre-morbid glycemic control modifies the interaction between acute hypoglycemia and mortality.

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Egi, Moritoki; Krinsley, James S; Maurer, Paula; Amin, Devendra N; Kanazawa, Tomoyuki; Ghandi, Shruti; Morita, Kiyoshi; Bailey, Michael; Bellomo, Rinaldo

2016-04-01

To study the impact of pre-morbid glycemic control on the association between acute hypoglycemia in intensive care unit (ICU) patients and subsequent hospital mortality in critically ill patients. We performed a multicenter, multinational, retrospective observational study of patients with available HbA1c levels within the 3-month period preceding ICU admission. We separated patients into three cohorts according to pre-admission HbA1c levels (<6.5, 6.5-7.9, ≥8.0%, respectively). Based on published data, we defined a glucose concentration of 40-69 mg/dL (2.2-3.8 mmol/L) as moderate hypoglycemia and <40 mg/dL (<2.2 mmol/L) as severe hypoglycemia. We applied logistic regression analysis to study the impact of pre-morbid glycemic control on the relationship between acute hypoglycemia and mortality. A total of 3084 critically ill patients were enrolled in the study. Among these patients, with increasing HbA1c levels from <6.5, to 6.5-7.9, and to ≥8.0%, the incidence of both moderate (3.8, 11.1, and 16.4%, respectively; p < 0.001) and severe (0.9, 2.5, and 4.3%, respectively; p < 0.001) hypoglycemia progressively and significantly increased. The relationship between the occurrence of hypoglycemic episodes in the ICU and in-hospital mortality was independently and significantly affected by pre-morbid glucose control, as assessed by adjusted odds ratio (OR) and 95 % confidence interval (CI) for hospital mortality: (1) moderate hypoglycemia: in patients with <6.5, 6.5-7.9, and ≥8.0 % of HbA1c level-OR 0.54, 95% CI 0.25-1.16; OR 0.82, 95 % CI 0.33-2.05; OR 3.42, 95 % CI 1.29-9.06, respectively; (2) severe hypoglycemia: OR 1.50, 95% CI 0.42-5.33; OR 1.59, 95% CI 0.36-7.10; OR 23.46, 95% CI 5.13-107.28, respectively (interaction with pre-morbid glucose control, p = 0.009). We found that the higher the glucose level before admission to the ICU, the higher the mortality risk when patients experienced hypoglycemia. In critically ill patients, chronic pre

Hypoglycemia associated with refeeding syndrome in a cat.

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DeAvilla, Marisa D; Leech, Elizabeth B

2016-11-01

To describe the clinical presentation and biochemical abnormalities occurring during the successful treatment of refeeding syndrome in a cat. A 2-year-old neutered male domestic shorthair cat presented after having been missing for 12 weeks. The cat had clinical signs of severe starvation. Common complications developed during refeeding (eg, hypophosphatemia, hypokalemia, and hemolytic anemia). The cat also developed hypoglycemia, a complication common in people but not previously reported in a cat. Hypoglycemia and electrolyte deficiencies were managed with intravenous supplementation. The cat was successfully treated and was discharged alive 7 days after presentation. Hypoglycemia has not been reported previously as a complication of refeeding in a cat. Frequent monitoring of electrolyte, mineral, and blood glucose concentrations is essential to successful management of refeeding syndrome. The ideal refeeding strategy is unknown at this time. Evidence suggests that a diet low in carbohydrate decreases the likelihood of metabolic derangements commonly associated with refeeding. © Veterinary Emergency and Critical Care Society 2016.

Sustained Reduction in Severe Hypoglycemia in Adults With Type 1 Diabetes Complicated by Impaired Awareness of Hypoglycemia: 2-Year Follow-up in the HypoCOMPaSS Randomized Clinical Trial.

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Little, Stuart A; Speight, Jane; Leelarathna, Lalantha; Walkinshaw, Emma; Tan, Horng Kai; Bowes, Anita; Lubina-Solomon, Alexandra; Chadwick, Thomas J; Stocken, Deborah D; Brennand, Catherine; Marshall, Sally M; Wood, Ruth; Kerr, David; Flanagan, Daniel; Heller, Simon R; Evans, Mark L; Shaw, James A M

2018-04-16

Severe hypoglycemia is a feared complication of type 1 diabetes; yet, few trials have targeted prevention using optimized self-management (educational, therapeutic, and technological support). We aimed to investigate whether improved awareness and reduced severe hypoglycemia, achieved during an intensive randomized clinical trial (RCT), were sustained after return to routine care. Ninety-six adults with type 1 diabetes (29 ± 12 years' duration) and impaired awareness of hypoglycemia at five U.K. tertiary referral diabetes centers were recruited into a 24-week 2 × 2 factorial RCT (HypoCOMPaSS). Participants were randomized to pump (continuous subcutaneous insulin infusion [CSII]) or multiple daily injections (MDIs) and real-time continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose (SMBG), with equal education/attention to all groups. At 24 weeks, participants returned to routine care with follow-up until 24 months, including free choice of MDI/CSII; RT-CGM vs. SMBG comparison continued to 24 months. Primary outcome was mean difference (baseline to 24 months [between groups]) in hypoglycemia awareness. Improvement in hypoglycemia awareness was sustained (Gold score at baseline 5.1 ± 1.1 vs. 24 months 3.7 ± 1.9; P diabetes complicated by impaired awareness of hypoglycemia. © 2018 by the American Diabetes Association.

Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers

DEFF Research Database (Denmark)

Nauck, Michael A; Heimesaat, Markus M; Behle, Kai

2002-01-01

and neuroglucopenic symptoms were assessed, and cognitive function was tested at each plateau. Insulin secretion rates were estimated by deconvolution (two-compartment model of C-peptide kinetics). At insulin concentrations of approximately 45 mU/liter, glucose infusion rates were similar with and without GLP-1 (P......Glucagon-like peptide 1 (GLP-1) and analogues are being evaluated as a new therapeutic principle for the treatment of type 2 diabetes. GLP-1 suppresses glucagon secretion, which could lead to disturbances of hypoglycemia counterregulation. This has, however, not been tested. Nine healthy volunteers.......97). The other counterregulatory hormones and autonomic or neuroglucopenic symptom scores increased, and cognitive functions decreased with decreasing glucose concentrations, but there were no significant differences comparing experiments with GLP-1 or placebo, except for a significant reduction of GH responses...

Nonislet Cell Tumor Hypoglycemia in a Patient with Adrenal Cortical Carcinoma

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Se Won Kim

2016-01-01

Full Text Available Nonislet cell tumor hypoglycemia (NICTH is a rare but serious paraneoplastic syndrome in which a tumor secretes incompletely processed precursors of insulin-like growth factor-II (IGF-II, causing hypoglycemia. Here, we report an exceptional case of NICTH caused by nonfunctioning adrenocortical carcinoma in a 39-year-old male with recurrent hypoglycemia. The patient’s serum IGF-II/IGF-I ratio had increased to 27.8. The serum level of the IGF-II/IGF-I ratio was normalized after removal of the tumor, and the hypoglycemic attacks no longer occurred after the operation.

[Metabolic control in the critically ill patient an update: hyperglycemia, glucose variability hypoglycemia and relative hypoglycemia].

Science.gov (United States)

Pérez-Calatayud, Ángel Augusto; Guillén-Vidaña, Ariadna; Fraire-Félix, Irving Santiago; Anica-Malagón, Eduardo Daniel; Briones Garduño, Jesús Carlos; Carrillo-Esper, Raúl

Metabolic changes of glucose in critically ill patients increase morbidity and mortality. The appropriate level of blood glucose has not been established so far and should be adjusted for different populations. However concepts such as glucose variability and relative hypoglycemia of critically ill patients are concepts that are changing management methods and achieving closer monitoring. The purpose of this review is to present new data about the management and metabolic control of patients in critical areas. Currently glucose can no longer be regarded as an innocent element in critical patients; both hyperglycemia and hypoglycemia increase morbidity and mortality of patients. Protocols and better instruments for continuous measurement are necessary to achieve the metabolic control of our patients. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Fear of hypoglycemia and its clinical significance: a case-control study

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Elena Georgievna Starostina

2013-11-01

Full Text Available Aim. To assess the prevalence of fear of hypoglycemia, its clinical features and influence on diabetes compensation. Materials and Methods. A cross-sectional study was conducted with 200 sequentially enrolled participants with type 2 diabetes mellitus (T2DM; n=139 and type 1 diabetes mellitus (T1DM; n=61. Patients were screened for psychiatric disorders with appropriate inventory and examined by a psychiatrist. Subjects identified as those with fear of hypoglycemia (n=12 formed the study group, while control group was assembled of individuals without phobic signs, matched for gender, age, type and duration of diabetes and concomitant psychiatric disorders. Results. Prevalence of fear of hypoglycemia was estimated at 6%, being consistently higher in patients with T1DM (16.1% vs. T2DM (1%; p=0.0002. Fear of hypoglycemia was associated with higher median HbA1c (9.4% [8.6 ; 9.9] vs. 8.2% [6.8 ; 9.3], p

Hypoglycemia in pregnant women with type 1 diabetes - Predictors and role of metabolic control

DEFF Research Database (Denmark)

Nielsen, L.R.; Johansen, M.; Pedersen-Bjergaard, U.

2008-01-01

OBJECTIVE- In pregnancy with type 1 diabetes, we evaluated occurrence of mild and severe hypoglycemia and analyzed the influence of strict metabolic control, nausea, Vomiting, and other potential predictors of occurrence of severe hypoglycemia. RESEARCH DESIGN AND METHODS- A prospective...... awareness or unawareness (3.2 [1.2-8.2]) as independent predictors for severe hypoglycemia. CONCLUSIONS - In pregnancy with type 1 diabetes, the incidence of mild and severe hypoglycemia was highest in early pregnancy, although metabolic control was tighter in the last part of pregnancy. Predictors...... observational study of 108 consecutive pregnant women with type 1 diabetes was conducted. At 8, 14, 21, 27, and 33 weeks of gestation, patients performed self-monitored plasma glucose (SMPG) (eight/day) for 3 days and completed a questionnaire on nausea, vomiting, hypoglycemia awareness, and history of mild...

Diffuse nesidioblastosis diagnosed on a Ga-68 DOTATATE positron emission tomography/computerized tomography

International Nuclear Information System (INIS)

Arun, Sasikumar; Mittal, Bhagwant Rai; Shukla, Jaya; Bhattacharya, Anish; Kumar, Praveen

2013-01-01

The authors describe a 50 days old pre-term infant with persistent hyperinsulinemic hypoglycemia of infancy in whom 68 Ga DOTATATE positron emission tomography/computerized tomography scan showed diffusely increased tracer uptake in the entire pancreas with no abnormal tracer uptake anywhere else in the body, suggestive of a diffuse variant of nesidioblastosis. (author)

Is Low Blood Glucose (Hypoglycemia) Dangerous?

Science.gov (United States)

... pills. In general, hypoglycemia is defined as a blood glucose level below 70 mg/dl. Low blood glucose is ... glucose. Always carry carbohydrate foods for treatment. Check blood glucose levels again in 15 minutes, and repeat treatment if ...

Self-monitoring of blood glucose is associated with problem-solving skills in hyperglycemia and hypoglycemia.

Science.gov (United States)

Wang, Jing; Zgibor, Janice; Matthews, Judith T; Charron-Prochownik, Denise; Sereika, Susan M; Siminerio, Linda

2012-01-01

The purpose of this study was to examine the association between self-monitoring of blood glucose (SMBG) and problem-solving skills in response to detected hyperglycemia and hypoglycemia among patients with type 2 diabetes. Data were obtained from the American Association of Diabetes Educators Outcome System, implemented in 8 diabetes self-management education programs in western Pennsylvania. SMBG was measured by asking patients how often they checked, missed checking, or checked blood glucose later than planned. Problem-solving skill was measured by asking how often they modified their behaviors after detecting high or low blood glucose. Most patients checked their blood glucose at least once per day. However, when blood glucose was high or low, many of them reported doing nothing, and only some of them resolved the problem. There were significant associations between self-monitoring of blood glucose and problem-solving skills for hyperglycemia and hypoglycemia, after controlling for age, gender, ethnicity, education, and time since diagnosis. Patients reported poor problem-solving skills when detecting hyperglycemia and hypoglycemia via SMBG. Patients need to learn problem-solving skills along with SMBG training to achieve glycemic control.

Combined acute hyperglycemic and hyperinsulinemic clamp induced profibrotic and proinflammatory responses in the kidney.

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Mariappan, Meenalakshmi M; DeSilva, Kristin; Sorice, Gian Pio; Muscogiuri, Giovanna; Jimenez, Fabio; Ahuja, Seema; Barnes, Jefferey L; Choudhury, Goutam Ghosh; Musi, Nicolas; DeFronzo, Ralph; Kasinath, Balakuntalam S

2014-02-01

Increase in matrix protein content in the kidney is a cardinal feature of diabetic kidney disease. While renal matrix protein content is increased by chronic hyperglycemia, whether it is regulated by acute elevation of glucose and insulin has not been addressed. In this study, we aimed to evaluate whether short duration of combined hyperglycemia and hyperinsulinemia, mimicking the metabolic environment of prediabetes and early type 2 diabetes, induces kidney injury. Normal rats were subjected to either saline infusion (control, n = 4) or 7 h of combined hyperglycemic-hyperinsulinemic clamp (HG+HI clamp; n = 6). During the clamp, plasma glucose and plasma insulin were maintained at about 350 mg/dl and 16 ng/ml, respectively. HG+HI clamp increased the expression of renal cortical transforming growth factor-β (TGF-β) and renal matrix proteins, laminin and fibronectin. This was associated with the activation of SMAD3, Akt, mammalian target of rapamycin (mTOR) complexes, and ERK signaling pathways and their downstream target events in the initiation and elongation phases of mRNA translation, an important step in protein synthesis. Additionally, HG+HI clamp provoked renal inflammation as shown by the activation of Toll-like receptor 4 (TLR4) and infiltration of CD68-positive monocytes. Urinary F2t isoprostane excretion, an index of renal oxidant stress, was increased in the HG+HI clamp rats. We conclude that even a short duration of hyperglycemia and hyperinsulinemia contributes to activation of pathways that regulate matrix protein synthesis, inflammation, and oxidative stress in the kidney. This finding could have implications for the control of short-term rises in blood glucose in diabetic individuals at risk of developing kidney disease.

Hypoglycemic Exposure and Risk of Asymptomatic Hypoglycemia in Type 1 Diabetes assessed by Continuous Glucose Monitoring

DEFF Research Database (Denmark)

Henriksen, Marie Moth; Andersen, Henrik Ullits; Thorsteinsson, Birger

2018-01-01

: To explore the association between hypoglycemic exposure and proportion of asymptomatic hypoglycemia and relation to risk of severe hypoglycemia. Design: Prospective observational trial. Setting: Outpatient clinic. Patients: 153 unselected subjects with type 1 diabetes mellitus (T1D). Intervention: Six days...... of blinded continuous glucose monitoring (CGM) and recording of hypoglycemia symptoms. Main Outcome Measure: Proportion of asymptomatic hypoglycemic events (≤70 mg/dl). Results: Patients were grouped by the number of hypoglycemic events during the recording period (group 1: 1 event, group 2: 2-3 events...... positively associated with risk of severe hypoglycemia (incidence rate ratio (IRR) 1.3 (95% CI 1.1-1.5); p=0.003). Group 4 consisted of patients characterized by classical risk factors of severe hypoglycemia (longer duration of diabetes, lower HbA1c and more frequent impaired awareness of hypoglycemia...

PEPCK-C reexpression in the liver counters neonatal hypoglycemia in Pck1 del/del mice, unmasking role in non-gluconeogenic tissues.

Science.gov (United States)

Semakova, Jana; Hyroššová, Petra; Méndez-Lucas, Andrés; Cutz, Ernest; Bermudez, Jordi; Burgess, Shawn; Alcántara, Soledad; Perales, José C

2017-02-01

Whole body cytosolic phosphoenolpyruvate carboxykinase knockout (PEPCK-C KO) mice die early after birth with profound hypoglycemia therefore masking the role of PEPCK-C in adult, non-gluconeogenic tissues where it is expressed. To investigate whether PEPCK-C deletion in the liver was critically responsible for the hypoglycemic phenotype, we reexpress this enzyme in the liver of PEPCK-C KO pups by early postnatal administration of PEPCK-C-expressing adenovirus. This maneuver was sufficient to partially rescue hypoglycemia and allow the pups to survive and identifies the liver as a critical organ, and hypoglycemia as the critical pathomechanism, leading to early postnatal death in the whole-body PEPCK-C knockout mice. Pathology assessment of survivors also suggest a possible role for PEPCK-C in lung maturation and muscle metabolism.

Innovations and Challenges of Implementing a Glucose Gel Toolkit for Neonatal Hypoglycemia.

Science.gov (United States)

Hammer, Denise; Pohl, Carla; Jacobs, Peggy J; Kaufman, Susan; Drury, Brenda

2018-05-24

Transient neonatal hypoglycemia occurs most commonly in newborns who are small for gestational age, large for gestational age, infants of diabetic mothers, and late preterm infants. An exact blood glucose value has not been determined for neonatal hypoglycemia, and it is important to note that poor neurologic outcomes can occur if hypoglycemia is left untreated. Interventions that separate mothers and newborns, as well as use of formula to treat hypoglycemia, have the potential to disrupt exclusive breastfeeding. To determine whether implementation of a toolkit designed to support staff in the adaptation of the practice change for management of newborns at risk for hypoglycemia, that includes 40% glucose gel in an obstetric unit with a level 2 nursery will decrease admissions to the Intermediate Care Nursery, and increase exclusive breastfeeding. This descriptive study used a retrospective chart review for pre/postimplementation of the Management of Newborns at Risk for Hypoglycemia Toolkit (Toolkit) using a convenience sample of at-risk newborns in the first 2 days of life to evaluate the proposed outcomes. Following implementation of the Toolkit, at-risk newborns had a clinically but not statistically significant 6.5% increase in exclusive breastfeeding and a clinically but not statistically significant 5% decrease in admissions to the Intermediate Care Nursery. The Toolkit was designed for ease of staff use and to improve outcomes for the at-risk newborn. Future research includes replication at other level 2 and level 1 obstetric centers and investigation into the number of 40% glucose gel doses that can safely be administered.

The current status of treatment-related severe hypoglycemia in Japanese patients with diabetes mellitus: A report from the committee on a survey of severe hypoglycemia in the Japan Diabetes Society.

Science.gov (United States)

Namba, Mitsuyoshi; Iwakura, Toshio; Nishimura, Rimei; Akazawa, Kohei; Matsuhisa, Munehide; Atsumi, Yoshihito; Satoh, Jo; Yamauchi, Toshimasa

2018-03-02

Despite great strides in pharmacotherapy for diabetes, there is increasing concern over the risk of hypoglycemia in patients with diabetes receiving pharmacotherapy as they become increasingly older. This has prompted the Japan Diabetes Society (JDS) to initiate a survey on the current status of severe hypoglycemia in clinical settings. In July 2015, following approval from the JDS Scientific Survey/Research Ethics Committee, the JDS extended an invitation to executive educators, who represented a total of 631 healthcare facilities accredited by the JDS for diabetes education, to participate in the proposed survey. Of these, those who expressed their willingness to participate in the survey were sent an application form required for obtaining ethical approval at these healthcare facilities and were then asked, following approval, to enter relevant clinical data on an unlinked, anonymous basis in a web-based registry. The current survey was fully funded by the JDS Scientific Survey/Research Committee. A case registry (clinical case database) was launched after facility-specific information (healthcare facility database) was collected from all participating facilities and after informed consent was obtained from all participating patients. With severe hypoglycemia defined as the "presence of hypoglycemic symptoms requiring assistance from another person to treat and preferably venous plasma glucose levels at onset/diagnosis of disease or at presentation clearly less than 60 mg/dL (capillary whole blood glucose, less than 50 mg/dL)", the current survey was conducted between April 1, 2014 and March 31, 2015, during which facility-specific information was collected from a total of 193 facilities with a total of 798 case reports collected from 113 facilities. Of the 193 respondent facilities, 149 reported having an emergency department as well, with the median number of patients who required emergency transportation services to reach these facilities totaling 4

Tratamiento del insulinoma con diazóxido Insulinoma treated with diazoxide

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M. V. Mateu

2003-01-01

Full Text Available Los insulinomas son tumores pancreáticos de las células beta que segregan insulina en cantidad suficiente como para producir hipoglucemia. Habitualmente benignos se manifiestan como adenomas solitarios, y en menor medida como microadenomas múltiples o carcinomas. Con una incidencia anual de un caso por millón de habitantes, generalmente en adultos de más de 30 años, se localizan con mayor frecuencia en el cuerpo y cola del páncreas. El diagnóstico se realiza sobre la base de los síntomas, la glucemia por debajo de 50mg% y niveles elevados de insulina plasmática y péptido C en ayunas. El mejor método preoperatorio para localizar el tumor es la arteriografía subselectiva del tronco celíaco. La mayoría de los adenomas que no logran evidenciarse por estudios por imágenes se diagnostican durante la cirugía. El tratamiento de elección del insulinoma es la cirugía. Cuando ésta fracasa o se contraindica, se utiliza tratamiento médico con diazóxido. Presentamos un caso de un paciente con un insulinoma que fue tratado médicamente, con excelente respuesta, realizando una actualización de las manifestaciones clínicas, los métodos diagnósticos y las opciones terapéuticas de una enfermedad muy poco frecuente.Insulinomas are islet cell tumors of the pancreas that produce hypoglycemia due to inappropriate insulin secretion. They appear generally as solitary adenomas, and less commonly as multifocal microadenomas or malignant insulinomas. Their incidence is approximately one case per 1 million population per year, and they appear mostly in patients above thirty years old. They are mainly situated in the pancreas tail or body. The diagnosis is based on the symptoms related to hypoglycemia, a blood glucose level under 50mg% and high levels of fast insulin and C-peptide. Selective angiography is the best preoperative procedure to localize the tumor. Occult adenomas, which cannot be represented by preoperative imaging diagnosis, are

Impact of hypoglycemia on patients with type 2 diabetes mellitus and their quality of life, work productivity, and medication adherence

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Lopez JMS

2014-05-01

Full Text Available Janice MS Lopez,1 Kathy Annunziata,2 Robert A Bailey,1 Marcia FT Rupnow,1 Donald E Morisky31Janssen Scientific Affairs, LLC, Raritan, NJ, 2Kantar Health, Princeton, NJ, 3University of California at Los Angeles Fielding School of Public Health, Los Angeles, CA, USABackground: The purpose of this study was to determine the characteristics of adults with type 2 diabetes mellitus (T2DM that correlate with greater risk of hypoglycemia and determine the impact of hypoglycemia on health-related quality of life, work productivity, and medication adherence from a patient perspective.Methods: Data from a large web-based survey were retrospectively analyzed. Adults with a diagnosis of T2DM taking antihyperglycemic agents were included in the analysis. Participants with knowledge of their hypoglycemic history were divided into three groups: those experiencing recent hypoglycemia (previous 3 months, those experiencing nonrecent hypoglycemia, and those never experiencing hypoglycemia.Results: Of the participants with T2DM taking antihyperglycemic agents who were knowledgeable of their hypoglycemia history, 55.7% had ever experienced hypoglycemia. Of those, 52.7% had recent hypoglycemia. Compared with those who never experienced hypoglycemia, those who experienced hypoglycemia tended to: be younger; be more aware of their glycated hemoglobin (HbA1c levels; have higher HbA1c levels; have a higher body mass index; have higher Charlson Comorbidity Index scores; be on insulin, sulfonylureas, and/or glucagon-like peptide-1 agonists; and be less adherent to their antihyperglycemic agents. Hypoglycemia interfered with social activities, caused more missed work (absenteeism, more impairment while at work (presenteeism, and decreased overall work productivity compared with patients who had never experienced hypoglycemia. Overall health-related quality of life, as determined by the Short Form-36 health questionnaire, was negatively impacted by hypoglycemia. Both

Hypoglycemia induced changes in cholinergic receptor expression in the cerebellum of diabetic rats

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Anju TR

2010-02-01

Full Text Available Abstract Glucose homeostasis in humans is an important factor for the functioning of nervous system. Hypoglycemia and hyperglycemia is found to be associated with central and peripheral nerve system dysfunction. Changes in acetylcholine receptors have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS. In the present study we showed the effects of insulin induced hypoglycemia and streptozotocin induced diabetes on the cerebellar cholinergic receptors, GLUT3 and muscle cholinergic activity. Results showed enhanced binding parameters and gene expression of Muscarinic M1, M3 receptor subtypes in cerebellum of diabetic (D and hypoglycemic group (D + IIH and C + IIH. α7nAchR gene expression showed a significant upregulation in diabetic group and showed further upregulated expression in both D + IIH and C + IIH group. AchE expression significantly upregulated in hypoglycemic and diabetic group. ChAT showed downregulation and GLUT3 expression showed a significant upregulation in D + IIH and C + IIH and diabetic group. AchE activity enhanced in the muscle of hypoglycemic and diabetic rats. Our studies demonstrated a functional disturbance in the neuronal glucose transporter GLUT3 in the cerebellum during insulin induced hypoglycemia in diabetic rats. Altered expression of muscarinic M1, M3 and α7nAchR and increased muscle AchE activity in hypoglycemic rats in cerebellum is suggested to cause cognitive and motor dysfunction. Hypoglycemia induced changes in ChAT and AchE gene expression is suggested to cause impaired acetycholine metabolism in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. The results shows that cerebellar cholinergic neurotransmission is impaired during hyperglycemia and hypoglycemia and the hypoglycemia is causing more prominent imbalance in cholinergic neurotransmission which is suggested to be a cause of cerebellar

Fasting adaptation in idiopathic ketotic hypoglycemia: a mismatch between glucose production and demand

NARCIS (Netherlands)

Huidekoper, Hidde H.; Duran, Marinus; Turkenburg, Marjolein; Ackermans, Mariëtte T.; Sauerwein, Hans P.; Wijburg, Frits A.

2008-01-01

In order to study the pathophysiology of hypoglycemia in idiopathic ketotic hypoglycemia (KH), glucose kinetics during fasting in patients with KH were determined. A fasting test was performed in 12 children with previously documented KH. Besides determination of glucoregulatory hormones, plasma

Fear of Hypoglycemia in Parents of Young Children with Type 1 Diabetes Mellitus

OpenAIRE

Patton, Susana R.; Dolan, Lawrence M.; Henry, Racquel; Powers, Scott W.

2008-01-01

The current study examined fear of hypoglycemia in 81 mothers and 64 fathers of young children with type 1 diabetes (T1DM) using the Hypoglycemia Fear Survey-Parents of Young Children (HFS-P-YC possible range=26–130).

Impact of retrospective calibration algorithms on hypoglycemia detection in newborn infants using continuous glucose monitoring.

Science.gov (United States)

Signal, Matthew; Le Compte, Aaron; Harris, Deborah L; Weston, Philip J; Harding, Jane E; Chase, J Geoffrey

2012-10-01

Neonatal hypoglycemia is common and may cause serious brain injury. Diagnosis is by blood glucose (BG) measurements, often taken several hours apart. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing the number of BG measurements. Calibration algorithms convert sensor signals into CGM output. Thus, these algorithms directly affect measures used to quantify hypoglycemia. This study was designed to quantify the effects of recalibration and filtering of CGM data on measures of hypoglycemia (BG neonates. CGM data from 50 infants were recalibrated using an algorithm that explicitly recognized the high-accuracy BG measurements available in this study. CGM data were analyzed as (1) original CGM output, (2) recalibrated CGM output, (3) recalibrated CGM output with postcalibration median filtering, and (4) recalibrated CGM output with precalibration median filtering. Hypoglycemia was classified by number of episodes, duration, severity, and hypoglycemic index. Recalibration increased the number of hypoglycemic events (from 161 to 193), hypoglycemia duration (from 2.2% to 2.6%), and hypoglycemic index (from 4.9 to 7.1 μmol/L). Median filtering postrecalibration reduced hypoglycemic events from 193 to 131, with little change in duration (from 2.6% to 2.5%) and hypoglycemic index (from 7.1 to 6.9 μmol/L). Median filtering prerecalibration resulted in 146 hypoglycemic events, a total duration of hypoglycemia of 2.6%, and a hypoglycemic index of 6.8 μmol/L. Hypoglycemia metrics, especially counting events, are heavily dependent on CGM calibration BG error, and the calibration algorithm. CGM devices tended to read high at lower levels, so when high accuracy calibration measurements are available it may be more appropriate to recalibrate the data.

Continuous glucose monitoring in newborn infants: how do errors in calibration measurements affect detected hypoglycemia?

Science.gov (United States)

Thomas, Felicity; Signal, Mathew; Harris, Deborah L; Weston, Philip J; Harding, Jane E; Shaw, Geoffrey M; Chase, J Geoffrey

2014-05-01

Neonatal hypoglycemia is common and can cause serious brain injury. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing blood glucose (BG) measurements. Calibration algorithms use BG measurements to convert sensor signals into CGM data. Thus, inaccuracies in calibration BG measurements directly affect CGM values and any metrics calculated from them. The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia metrics in newborn infants. Data from 155 babies were used. Two timing and 3 BG meter error models (Abbott Optium Xceed, Roche Accu-Chek Inform II, Nova Statstrip) were created using empirical data. Monte-Carlo methods were employed, and each simulation was run 1000 times. Each set of patient data in each simulation had randomly selected timing and/or measurement error added to BG measurements before CGM data were calibrated. The number of hypoglycemic events, duration of hypoglycemia, and hypoglycemic index were then calculated using the CGM data and compared to baseline values. Timing error alone had little effect on hypoglycemia metrics, but measurement error caused substantial variation. Abbott results underreported the number of hypoglycemic events by up to 8 and Roche overreported by up to 4 where the original number reported was 2. Nova results were closest to baseline. Similar trends were observed in the other hypoglycemia metrics. Errors in blood glucose concentration measurements used for calibration of CGM devices can have a clinically important impact on detection of hypoglycemia. If CGM devices are going to be used for assessing hypoglycemia it is important to understand of the impact of these errors on CGM data. © 2014 Diabetes Technology Society.

The accuracy of home glucose meters in hypoglycemia.

Science.gov (United States)

Sonmez, Alper; Yilmaz, Zeynep; Uckaya, Gokhan; Kilic, Selim; Tapan, Serkan; Taslipinar, Abdullah; Aydogdu, Aydogan; Yazici, Mahmut; Yilmaz, Mahmut Ilker; Serdar, Muhittin; Erbil, M Kemal; Kutlu, Mustafa

2010-08-01

Home glucose meters (HGMs) may not be accurate enough to sense hypoglycemia. We evaluated the accuracy and the capillary and venous comparability of five different HGMs (Optium Xceed [Abbott Diabetes Care, Alameda, CA, USA], Contour TS [Bayer Diabetes Care, Basel, Switzerland], Accu-Chek Go [Roche Ltd., Basel, Switzerland], OneTouch Select [Lifescan, Milpitas, CA, USA], and EZ Smart [Tyson Bioresearch Inc., Chu-Nan, Taiwan]) in an adult population. The insulin hypoglycemia test was performed to 59 subjects (56 males; 23.6 +/- 3.2 years old). Glucose was measured from forearm venous blood and finger capillary samples both before and after regular insulin (0.1 U/kg) was injected. Venous samples were analyzed in the reference laboratory by the hexokinase method. In vitro tests for method comparison and precision analyses were also performed by spiking the glucose-depleted venous blood. All HGMs failed to sense hypoglycemia to some extend. EZ Smart was significantly inferior in critical error Zone D, and OneTouch Select was significantly inferior in the clinically unimportant error Zone B. Accu-Chek Go, Optium Xceed, and Contour TS had similar performances and were significantly better than the other two HGMs according to error grid analysis or International Organization for Standardization criteria. The in vitro tests were consistent with the above clinical data. The capillary and venous consistencies of Accu-Chek Go and OneTouch Select were better than the other HGMs. The present results show that not all the HGMs are accurate enough in low blood glucose levels. The patients and the caregivers should be aware of these restrictions of the HGMs and give more credit to the symptoms of hypoglycemia than the values obtained by the HGMs. Finally, these results indicate that there is a need for the revision of the accuracy standards of HGMs in low blood glucose levels.

Current perspectives on neonatal hypoglycemia, its management, and cerebral injury risk

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Chandran S

2015-02-01

Full Text Available Suresh Chandran,1–4 Victor Samuel Rajadurai,1–3 Abdul Alim Abdul Haium,1–3 Khalid Hussain5,6 1Department of Neonatology, KK Women’s and Children’s Hospital, Singapore; 2Duke-NUS Graduate School of Medicine, Singapore; 3Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 4Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 5Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, 6The Institute of Child Health, University College London, London, UK Abstract: Glucose is an essential substrate for mammalian cells; in particular, the brain needs glucose continuously as a primary source of energy. Hypoglycemia is the most common biochemical finding in the neonatal period. However, despite the common occurrence, there is still controversy on the definition of hypoglycemia in the newborn period. This has led to the development of guidelines designed to identify infants “at-risk” and the implementation of an “operational threshold” for physicians to consider intervention. In healthy term infants, the optimal hormonal and metabolic adaptations during the immediate neonatal period ensure an adequate energy substrate for the vital organs, whereas the abnormal glucose homeostasis observed in preterm and growth-retarded infants is multifactorial in origin. For these high-risk infants, it is important to identify, screen, and prevent significant hypoglycemia. Detailed investigations are warranted in infants with severe and persistent hypoglycemia. Neonatal hypoglycemia is a major cause of brain injury. The speculated mechanisms of cellular injury include excitatory neurotoxins active at N-methyl-D-aspartate receptors, increased mitochondrial free radical generation with initiation of apoptosis and altered cerebral energetic characteristics. This hypoglycemic brain injury predominantly affects parieto-occipital regions causing

Hypoglycemia in Patients with Diabetes and Renal Disease

OpenAIRE

Alsahli, Mazen; Gerich, John E.

2015-01-01

This article summarizes our current knowledge of the epidemiology, pathogenesis, and morbidity of hypoglycemia in patients with diabetic kidney disease and reviews therapeutic limitations in this situation.

Hypoglycemia in Patients with Diabetes and Renal Disease.

Science.gov (United States)

Alsahli, Mazen; Gerich, John E

2015-05-13

This article summarizes our current knowledge of the epidemiology, pathogenesis, and morbidity of hypoglycemia in patients with diabetic kidney disease and reviews therapeutic limitations in this situation.

Incidence of Hypoglycemia in Patients With Low eGFR Treated With Insulin and Dextrose for Hyperkalemia.

Science.gov (United States)

Pierce, Dwayne A; Russell, Greg; Pirkle, James L

2015-12-01

Hyperkalemia is a potentially life-threatening condition that is common in kidney disease patients. Insulin is used to treat hyperkalemia, but may cause hypoglycemia, especially in kidney disease when insulin may be metabolized more slowly. We compared the rates of hypoglycemia in patients with low estimated glomerular filtration rate (eGFR) using high versus low doses of insulin for hyperkalemia to determine if lower doses of insulin would decrease the incidence of hypoglycemia. This was a retrospective study of hospitalized patients receiving intravenous insulin for hyperkalemia during a 6-month period. Patients with low eGFR were analyzed based on how much insulin they received: high dose (10 units, n = 78) versus low dose (5 units, n = 71). Postdose nadir blood glucose values were examined for up to 8 hours after the dose. The percentage of hypoglycemia (blood glucose ≤70 mg/dl) and a subset of severe hypoglycemia (blood glucose <50 mg/dl) were then reported for each dose group. A total of 149 doses were identified in patients with low eGFR. The rates of hypoglycemia were 16.7% and 19.7% (P = 0.79), respectively, among high-dose (n = 78) and low-dose (n = 71) groups. Rates of severe hypoglycemia were 8.9% and 7.0%, respectively (P = 0.90). More than 28% of hypoglycemic episodes with high doses occurred after 4 hours (median = 2.5 hours) compared with 14.3% with low doses (median = 2.38 hours). There was no difference in the rate of hypoglycemia or severe hypoglycemia between high or low doses of insulin in patients with low eGFR. We recommend monitoring up to 6 hours after insulin use in hyperkalemia. © The Author(s) 2015.

Symptomatic hypoglycemia causing brain injury in a term breast fed newborn following early discharge.

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Marwah, Ashish; Gathwala, Geeta

2011-12-01

Cerebral metabolism and functioning depends upon an adequate blood glucose supply which provides for majority of the brain's energy requirement. Studies from the past have shown that neonatal hypoglycemia is associated with acute and long term neurological sequelae. Early discharge without adequately established breast feeding may lead to feeding problems, post discharge hypoglycemia and its associated neurological complications. The authors describe one such case of an exclusively breast fed term newborn who presented on day 3 with symptomatic hypoglycemia and associated neurological injury.

Gcg-XTEN: an improved glucagon capable of preventing hypoglycemia without increasing baseline blood glucose.

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Nathan C Geething

2010-04-01

Full Text Available While the majority of current diabetes treatments focus on reducing blood glucose levels, hypoglycemia represents a significant risk associated with insulin treatment. Glucagon plays a major regulatory role in controlling hypoglycemia in vivo, but its short half-life and hyperglycemic effects prevent its therapeutic use for non-acute applications. The goal of this study was to identify a modified form of glucagon suitable for prophylactic treatment of hypoglycemia without increasing baseline blood glucose levels.Through application of the XTEN technology, we report the construction of a glucagon fusion protein with an extended exposure profile (Gcg-XTEN. The in vivo half-life of the construct was tuned to support nightly dosing through design and testing in cynomolgus monkeys. Efficacy of the construct was assessed in beagle dogs using an insulin challenge to induce hypoglycemia. Dose ranging of Gcg-XTEN in fasted beagle dogs demonstrated that the compound was biologically active with a pharmacodynamic profile consistent with the designed half-life. Prophylactic administration of 0.6 nmol/kg Gcg-XTEN to dogs conferred resistance to a hypoglycemic challenge at 6 hours post-dose without affecting baseline blood glucose levels. Consistent with the designed pharmacokinetic profile, hypoglycemia resistance was not observed at 12 hours post-dose. Importantly, the solubility and stability of the glucagon peptide were also significantly improved by fusion to XTEN.The data show that Gcg-XTEN is effective in preventing hypoglycemia without the associated hyperglycemia expected for unmodified glucagon. While the plasma clearance of this Gcg-XTEN has been optimized for overnight dosing, specifically for the treatment of nocturnal hypoglycemia, constructs with significantly longer exposure profiles are feasible. Such constructs may have multiple applications such as allowing for more aggressive insulin treatment regimens, treating hypoglycemia due to insulin

Long-Term Prediction of Severe Hypoglycemia in Type 1 Diabetes

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Henriksen, Marie Moth; Færch, Louise; Thorsteinsson, Birger

2016-01-01

BACKGROUND: Prediction of risk of severe hypoglycemia (SH) in patients with type 1 diabetes is important to prevent future episodes, but it is unknown if it is possible to predict the long-term risk of SH. The aim of the study is to assess if long-term prediction of SH is possible in type 1...... diabetes. METHODS: A follow-up study was performed with 98 patients with type 1 diabetes. At baseline and at follow-up, the patients filled in a questionnaire about diabetes history and complications, number of SH in the preceding year and state of awareness, and HbA1c and C-peptide levels were measured......-up. CONCLUSIONS: Long-term prediction of severe hypoglycemia in type 1 diabetes was not possible, although baseline hypoglycemia unawareness tended to remain a predictor for risk of SH at follow-up. Therefore, it is important repeatedly to assess the different risk factors of SH to determine the actual risk....

Prevention of acute/severe hypoglycemia-induced neuron death by lactate administration

OpenAIRE

Won, Seok Joon; Jang, Bong Geom; Yoo, Byung Hoon; Sohn, Min; Lee, Min Woo; Choi, Bo Young; Kim, Jin Hee; Song, Hong Ki; Suh, Sang Won

2012-01-01

Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who attempt tight control of blood glucose and may lead to cognitive dysfunction. Accumulating evidence from animal models suggests that hypoglycemia-induced neuronal death is not a simple result of glucose deprivation, but is instead the end result of a multifactorial process. In particular, the excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide adenine dinucleotide (NAD+...

Continuous glucose monitoring in newborn infants: how do errors in calibration measurements affect detected hypoglycemia?

OpenAIRE

Thomas, Felicity Louise; Signal, Mathew; Harris, Deborah L.; Weston, Philip J.; Harding, Jane E.; Shaw, Geoffrey M.; Chase, J. Geoffrey

2014-01-01

Neonatal hypoglycemia is common and can cause serious brain injury. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing blood glucose (BG) measurements. Calibration algorithms use BG measurements to convert sensor signals into CGM data. Thus, inaccuracies in calibration BG measurements directly affect CGM values and any metrics calculated from them. The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia me...

Endotoxemia-induced lymphocyte apoptosis is augmented by a hyperinsulinemic-euglycemic clamp

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Nielsen, Jeppe Sylvest; A, Larsson; Brix-Christensen, Vibeke

2005-01-01

BACKGROUND: Sepsis and endotoxemia are associated with lymphocyte apoptosis. This has been regarded as harmful, contributing to further immune suppression in already immune-compromised patients. Because normalization of blood glucose improves outcome in critically ill patients, the authors...... hypothesized that one of the effects of insulin and normoglycemia would be inhibition of lymphocyte apoptosis. Therefore, in this experimental study in pigs, the authors examined the separate and combined effects of acute endotoxemia and a hyperinsulinemic-euglycemic clamp (HEC) on lymphocyte apoptosis...... sections of each sample, the apoptosis of B and T lymphocytes were analyzed using stereologic methods: The number of apoptotic B and T cells was estimated by fluorescence immunohistochemistry with anti-active caspase-3 and either anti-CD21 (B lymphocytes) or anti-CD3epsilon (T lymphocytes). The number...

Hypoglycemia in Patients with Diabetes and Renal Disease

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Mazen Alsahli

2015-05-01

Full Text Available This article summarizes our current knowledge of the epidemiology, pathogenesis, and morbidity of hypoglycemia in patients with diabetic kidney disease and reviews therapeutic limitations in this situation.

Characterization of the concurrent metabolic changes in brain and plasma during insulin-induced moderate hypoglycemia using 1H NMR spectroscopy in juvenile rats.

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Ennis, Kathleen; Lusczek, Elizabeth; Rao, Raghavendra

2017-07-13

Treatment of hypoglycemia in children is currently based on plasma glucose measurements. This approach may not ensure neuroprotection since plasma glucose does not reflect the dynamic state of cerebral energy metabolism. To determine whether cerebral metabolic changes during hypoglycemia could be better characterized using plasma metabolomic analysis, insulin-induced acute hypoglycemia was induced in 4-week-old rats. Brain tissue and concurrent plasma samples were collected from hypoglycemic (N=7) and control (N=7) rats after focused microwave fixation to prevent post-mortem metabolic changes. The concentration of 29 metabolites in brain and 34 metabolites in plasma were determined using 1 H NMR spectroscopy at 700MHz and examined using partial least squares-discriminant analysis. The sensitivity of plasma glucose for detecting cerebral energy failure was assessed by determining its relationship to brain phosphocreatine. The brain and plasma metabolite profiles of the hypoglycemia group were distinct from the control group (brain: R 2 =0.92, Q 2 =0.31; plasma: R 2 =0.95, Q 2 =0.74). Concentration differences in glucose, ketone bodies and amino acids were responsible for the intergroup separation. There was 45% concordance between the brain and plasma metabolite profiles. Brain phosphocreatine correlated with brain glucose (control group: R 2 =0.86; hypoglycemia group: R 2 =0.59; pplasma glucose. The results confirm that plasma glucose is an insensitive biomarker of cerebral energy changes during hypoglycemia and suggest that a plasma metabolite profile is superior for monitoring cerebral metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

Fear of Hypoglycemia in Children and Adolescents and Their Parents with Type 1 Diabetes.

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Driscoll, Kimberly A; Raymond, Jennifer; Naranjo, Diana; Patton, Susana R

2016-08-01

Hypoglycemia is a frequent occurrence in children and adolescents with type 1 diabetes. A variety of efforts have been made to standardize the definition of hypoglycemia and to define one of its most significant psychosocial consequences-fear of hypoglycemia (FOH). In addition to documenting the experience of FOH in children and adolescents type 1 diabetes and their parents, studies have investigated the relations between FOH and glycemic control and diabetes technology use. This review provides a summary of the recent FOH literature as it applies to pediatric type 1 diabetes.

A Novel Algorithm in the Management of Hypoglycemia in Newborns

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Swapna Naveen

2014-01-01

Full Text Available Study Objective. To evaluate the safety of a new protocol in comparison to the standard protocol for managing hypoglycemia in neonates. Methods. Open label RCT-pilot study. Neonates admitted to NICU with hypoglycemia and requiring intravenous fluids were included. Fifty-seven eligible neonates were randomly allocated to either intervention group (starting fluids with 10% dextrose and increments of 1.5% or standard protocol group (GIR of 6 mg/kg/min with increments of 2 mg/kg/min till control of hypoglycemia. Primary outcome of the study was to know proportion of infants with subsequent hypoglycemia and hyperglycemia after enrolment. Results. The initial GIR (6 ± 0 mg/kg/min versus 4.8 ± 1.4 mg/kg/min, P < 0.001, the mean maximum GIR (6.7 ± 1.6 mg/kg/min versus 5.6 ± 2 mg/kg/min, P = 0.03, the maximum concentration of glucose infused (13.8 ± 2.9% versus 10.9 ± 1.9%, P < 0.001, and the total amount of glucose infused were significantly lower in the intervention group. The mean maximum blood sugar was significantly higher (129 ± 57 mg/dL versus 87 ± 30 mg/dL, P = 0.001 and there was a trend towards high proportion of infants with Hyperglycemia in the standard protocol group (n = 10, 39% versus n = 5, 16%, P = 0.07. The median difference between the highest and the lowest recorded sugar for any infant was significantly higher in the standard protocol group (median 93 mg/dL, IQR 52 to 147 mg/dL versus median 50 mg/dL, IQR 38 to 62.5 mg/dL, P = 0.03. Conclusion. A new and novel algorithm in the management of hypoglycemia in neonates is as safe as the standard protocol and requires further testing before routine implementation.

Influence of non-steady state during isoglycemic hyperinsulinemic clamp in hypertension. A LIFE substudy

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Olsen, M H; Andersen, U B; Wachtell, K

1999-01-01

We wanted to investigate whether time to steady state was reached within 2 h of insulin infusion during isoglycemic hyperinsulinemic clamp, comparing the glucose uptake index (M/IG) with Bergman's insulin sensitivity index (Sip). We performed a 2-h oral glucose tolerance test and a 3-h isoglycemic....... Because the 2-h M/IG correlated strongly with the 3-h Sip with relatively narrow limits of agreement, it is a good measure of insulin sensitivity. However, a 2-h clamp results in lower insulin sensitivity values in elderly, hypertensive patients due to the fact that steady state is not reached...

Hypoglycemia: a review of definitions used in clinical trials evaluating antihyperglycemic drugs for diabetes

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Balijepalli C

2017-05-01

Full Text Available Chakrapani Balijepalli,1,2 Eric Druyts,2 Gaye Siliman,2 Michel Joffres,1 Kristian Thorlund,2,3 Edward J Mills3 1Faculty of Health Sciences, Simon Fraser University, Burnaby, 2Precision Health Economics, Vancouver, BC, 3Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada Objective: To understand the severity and potential impact of heterogeneity in definitions of hypoglycemia used in diabetes research, we aimed to review the hypoglycemia definitions adopted in randomized controlled trials (RCTs.Methods: We reviewed 109 RCTs included in the Canadian Agency for Drugs and Technologies in Health reports for the second- and third-line therapy for the patients with type 2 diabetes (T2D.Results: Nearly 60% (n=66 of the studies reviewed presented the definitions for overall hypoglycemia, and another 20% (n=22 of the studies reported the results for hypoglycemia but did not report a definition. Among these 66 studies, only 9 (14% followed the American Diabetes Association/European Medicines Agency specified guidelines to define hypoglycemia, with an exact threshold of plasma glucose ≤3.9 mmol/L. Fifty-two of the 66 studies (79% used a threshold considerably lower than the recommended ≤3.9 mmol/L, and 16 studies used a threshold between 3.8 and 4.0 mmol/L. The proportion of the trials that used a cutoff value of <3.1 mmol/L appeared to be slightly similar among the more commonly used non-insulin treatments, GLP-1s (7 of 18 [39%], thiazolidinediones (TZDs; 6 of 11 [55%], DPP-4s (12 of 19 [64%], and sulfonylureas (11 of 20 [55%]. Among trials with intermediate-long-acting insulins (neutral protamine Hagedorn insulin, detemir, glargine, 7 of 26 trials (27% used a cutoff of <3.1 mmol/L. The definition of severe hypoglycemia was also subject to substantial heterogeneity, in both the utilized threshold and accompanying soft definitions.Conclusion: This review demonstrates

Late Pregnancy β Blocker Exposure and Risks of Neonatal Hypoglycemia and Bradycardia.

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Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Maeda, Ayumi; Fischer, Michael A; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2016-09-01

β blockers are widely used in the treatment of hypertensive disorders during pregnancy. These medications cross the placenta and may cause physiologic changes in neonates exposed in utero. We sought to define the risks of neonatal hypoglycemia and bradycardia associated with maternal exposure to β blockers at the time of delivery in a large, nationwide cohort of Medicaid beneficiaries. We used a cohort of 2 292 116 completed pregnancies linked to liveborn infants of Medicaid-enrolled women from 2003 to 2007. We examined the risks of neonatal hypoglycemia and neonatal bradycardia associated with maternal exposure to β blockers at the time of delivery. Propensity score matching was used to control for potential confounders including maternal demographics, obstetric and medical conditions, and exposure to other medications. There were 10 585 (0.5%) pregnancies exposed to β blockers at the time of delivery. The risk of neonatal hypoglycemia was 4.3% in the β blocker-exposed neonates versus 1.2% in the unexposed; the risk of neonatal bradycardia was 1.6% in the exposed versus 0.5% in the unexposed. After controlling for confounders, risk remained elevated for both neonatal hypoglycemia and bradycardia among exposed pregnancies versus unexposed (adjusted odds ratio, 1.68, 95% confidence interval, 1.50-1.89 and adjusted odds ratio, 1.29, 95% confidence interval, 1.07-1.55, respectively). Our findings suggest that neonates born to mothers exposed to β blockers in late pregnancy, including labetalol, are at elevated risk for neonatal hypoglycemia and bradycardia. Copyright © 2016 by the American Academy of Pediatrics.

Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

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Suk Chon

2011-02-01

Full Text Available BackgroundType B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans.MethodsTo evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy.ResultsIn the patient's pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%.ConclusionWe treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding.

Fear of hypoglycemia and its clinical significance: a case-control study

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Elena Georgievna Starostina; Elena Nikolaevna Moshnyaga

2013-01-01

Aim. To assess the prevalence of fear of hypoglycemia, its clinical features and influence on diabetes compensation.Materials and Methods. A cross-sectional study was conducted with 200 sequentially enrolled participants with type 2 diabetes mellitus (T2DM; n=139) and type 1 diabetes mellitus (T1DM; n=61). Patients were screened for psychiatric disorders with appropriate inventory and examined by a psychiatrist. Subjects identified as those with fear of hypoglycemia (n=12) formed the study gr...

Assessing fear of hypoglycemia in a population-based study among parents of children with type 1 diabetes - psychometric properties of the hypoglycemia fear survey - parent version.

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Haugstvedt, Anne; Wentzel-Larsen, Tore; Aarflot, Morten; Rokne, Berit; Graue, Marit

2015-01-19

In the treatment of childhood type 1 diabetes, being aware of the parents' fear of hypoglycemia is important, since the parents' fear may influence the management of treatment and the children's blood glucose regulation. The availability of proper instruments to assess the parents' fear of hypoglycemia is essential. Thus, the aim of this study was to examine the psychometric properties of the Hypoglycemia Fear Survey - Parent version (HFS-P). In a Norwegian population-based sample, 176 parents representing 102 children with type 1 diabetes (6-15 years old) completed the HFS-P, comprising a 15-item worry subscale and a 10-item behavior subscale. We performed exploratory and confirmatory factor analysis and further analysis of the scales' construct validity, content validity and reliability. The Norwegian version of the HFS-P had an acceptable factor structure and internal consistency for the worry subscale, whereas the structure and internal consistency of the behavior subscale was more questionable. The HFS-P subscales were significantly correlated (from moderately to weakly) with symptoms of emotional distress, as measured by the Hopkins Symptom Checklist - 25 items. The mothers scored higher than fathers on both HFS-P subscales, but the difference was not statistically significant for the worry subscale. The HFS-P worry subscale seems to be a valid scale for measuring anxiety-provoking aspects of hypoglycemia, and the validity of the HFS-P behavior subscale needs to be investigated further.

Influence of Hypoglycemia During The 100-G Oral Glucose Tolerance Test on Obstetrics Outcomes

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İlknur İnegöl Gümüş

2008-08-01

CONCLUSIONS: Women who experience hypoglycemia during the OGTT have a significantly higher incidence of gestational weight gain and higher neonatal birth weights as well. As a result if a pregnant has hypoglycemia during OGTT we should monitorize her and the fetus as well carefully.

High-Intensity Exercise as a Dishabituating Stimulus Restores Counterregulatory Responses in Recurrently Hypoglycemic Rodents.

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McNeilly, Alison D; Gallagher, Jennifer R; Huang, Jeffrey T-J; Ashford, Michael L J; McCrimmon, Rory J

2017-06-01

Hypoglycemia is a major adverse effect of insulin therapy for people with type 1 diabetes (T1D). Profound defects in the normal counterregulatory response to hypoglycemia explain the frequency of hypoglycemia occurrence in T1D. Defective counterregulation results to a large extent from prior exposure to hypoglycemia per se, leading to a condition called impaired awareness of hypoglycemia (IAH), the cause of which is unknown. In the current study, we investigate the hypothesis that IAH develops through a special type of adaptive memory referred to as habituation. To test this hypothesis, we used a novel intense stimulus (high-intensity exercise) to demonstrate two classic features of a habituated response, namely dishabituation and response recovery. We demonstrate that after recurrent hypoglycemia the introduction of a novel dishabituating stimulus (a single burst of high-intensity exercise) in male Sprague-Dawley rats restores the defective hypoglycemia counterregulatory response. In addition, the rats showed an enhanced response to the novel stimulus (response recovery). We make the further observation using proteomic analysis of hypothalamic extracts that high-intensity exercise in recurrently hypoglycemic rats increases levels of a number of proteins linked with brain-derived neurotrophic factor signaling. These findings may lead to novel therapeutic approaches for individuals with T1D and IAH. © 2017 by the American Diabetes Association.

Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain.

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Fournier, Jean-Pascal; Azoulay, Laurent; Yin, Hui; Montastruc, Jean-Louis; Suissa, Samy

2015-02-01

Tramadol is a weak opioid analgesic whose use has increased rapidly, and it has been associated with adverse events of hypoglycemia. To assess whether tramadol use, when compared with codeine use, is associated with an increased risk of hospitalization for hypoglycemia. A nested case-control analysis was conducted within the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database of all patients newly treated with tramadol or codeine for noncancer pain between 1998 and 2012. Cohort and case-crossover analyses were also conducted to assess consistency of the results. Cases of hospitalization for hypoglycemia were matched with up to 10 controls on age, sex, and duration of follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated comparing use of tramadol with codeine. A cohort analysis, with high-dimensional propensity score-adjusted hazard ratios (HRs) and 95% CIs, was performed comparing tramadol with codeine in the first 30 days after treatment initiation. Finally, a case-crossover analysis was also performed, in which exposure to tramadol in a 30-day risk period immediately before the hospitalization for hypoglycemia was compared with 11 consecutive 30-day control periods. Odds ratios and 95% CIs were estimated using conditional logistic regression analysis. The cohort included 334,034 patients, of whom 1105 were hospitalized for hypoglycemia during follow-up (incidence, 0.7 per 1000 per year) and matched to 11,019 controls. Compared with codeine, tramadol use was associated with an increased risk of hospitalization for hypoglycemia (OR, 1.52 [95% CI, 1.09-2.10]), particularly elevated in the first 30 days of use (OR, 2.61 [95% CI, 1.61-4.23]). This 30-day increased risk was confirmed in the cohort (HR, 3.60 [95% CI, 1.56-8.34]) and case-crossover analyses (OR, 3.80 [95% CI, 2.64-5.47]). The initiation of tramadol therapy is associated with an increased risk of hypoglycemia requiring

Stepwise Approach to Problematic Hypoglycemia in Korea: Educational, Technological, and Transplant Interventions

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Sang-Man Jin

2017-06-01

Full Text Available Impaired awareness of hypoglycemia has been found to be prevalent in 20% to 40% of people with type 1 diabetes. If a similar prevalence exists in Koreans with type 1 diabetes, at a minimum, thousands of people with type 1 diabetes suffer at least one unpredicted episode of severe hypoglycemia per year in Korea. For patients with problematic hypoglycemia, an evidence-based stepwise approach was suggested in 2015. The first step is structured education regarding multiple daily injections of an insulin analog, and the second step is adding a technological intervention, such as continuous subcutaneous insulin infusion or real-time continuous glucose monitoring. The next step is a sensor-augmented pump, preferably with a low glucose suspension feature or very frequent contact, and the final step is islet or pancreas transplantation. In Korea, however, none of these treatments are reimbursed by the National Health Insurance, and thus have not been widely implemented. The low prevalence of type 1 diabetes means that Korean physicians are relatively unfamiliar with the new technologies in this field. Therefore, the roles of new technologies and pancreas or islet transplantation in the treatment of problematic hypoglycemia need to be defined in the current clinical setting of Korea.

Acute Hypoglycemia Induces Painful Neuropathy and the Treatment of Coenzyme Q10

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Yan Ping Zhang

2016-01-01

Full Text Available Diabetic neuropathic pain is reduced with tight glycemic control. However, strict control increases the risk of hypoglycemic episodes, which are themselves linked to painful neuropathy. This study explored the effects of hypoglycemia-related painful neuropathy. Pretreatment with coenzyme Q10 (CoQ10 was performed to explore the preventive effect of CoQ10 on hypoglycemia-related acute neuropathic pain. Two strains of mice were used and 1 unit/kg of insulin was given to induce hypoglycemia. Mechanical sensitivity of hindpaw withdrawal thresholds was measured using von Frey filaments. Blood glucose levels were clamped at normal levels by joint insulin and glucose injection to test whether insulin itself induced hypersensitivity. Results suggest that the increased mechanical sensitivity after insulin injection is related to decreased blood glucose levels. When blood glucose levels remained at a normal level by the linked administration of insulin and glucose, mice demonstrated no significant change in mechanical sensitivity. Pretreatment with CoQ10 prevented neuropathic pain and the expression of the stress factor c-Fos. These results support the concept that pain in the diabetic scenario can be the result of hypoglycemia and not insulin itself. Additionally, pretreatment with CoQ10 may be a potent preventive method for the development of neuropathic pain.

Genetic variation and activity of the renin-angiotensin system and severe hypoglycemia in type 1 diabetes

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Pedersen-Bjergaard, U.; Dhamrait, S.S.; Sethi, A.A.

2008-01-01

BACKGROUND: The deletion-allele of the angiotensin-converting enzyme (ACE) gene and elevated ACE activity are associated with increased risk of severe hypoglycemia in type 1 diabetes. We explored whether genetic and phenotypic variations in other components of the renin-angiotensin system...... are similarly associated. METHODS: Episodes of severe hypoglycemia were recorded in 171 consecutive type 1 diabetic outpatients during a 1-year follow-up. Participants were characterized at baseline by gene polymorphisms in angiotensinogen, ACE, angiotensin-II receptor types 1 (AT1R) and 2 (AT2R), and by plasma...... associate with high risk of severe hypoglycemia in type 1 diabetes. A potential preventive effect of renin-angiotensin system blocking drugs in patients with recurrent severe hypoglycemia merits further investigation Udgivelsesdato: 2008/3...

Descriptions of health states associated with increasing severity and frequency of hypoglycemia: a patient-level perspective

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Harris SB

2013-09-01

Full Text Available Stewart B Harris,1 Kamlesh Khunti,2 Mona Landin-Olsson,3 Claus B Galbo-Jørgensen,4 Mette Bøgelund,4 Barrie Chubb,5 Jens Gundgaard,6 Marc Evans71Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; 2Diabetes Research Unit, University of Leicester, Leicester, UK; 3Department of Medicine, Helsingborg Hospital, Lund University, Lund, Sweden; 4Incentive, Holte Stationsvej, Holte, Denmark; 5EU Health Economics and Outcomes Research, Novo Nordisk Ltd, Crawley, UK; 6Health Economics and HTA, Novo Nordisk A/S, Søborg, Denmark; 7Department of Diabetes, University Hospital Llandough, Cardiff, UKAims: We sought to develop descriptions of health states associated with daytime and nocturnal hypoglycemia in a structured fashion from the patient's perspective under different combinations of severity and frequency of hypoglycemic events.Methods: An expert meeting followed by two patient focus groups was used to develop comprehensive descriptions of acute consequences of severe and non-severe, daytime and nocturnal hypoglycemia. Patients with diabetes (type 1 = 85, type 2 = 162 from a survey panel then validated these descriptions and assessed how often they worried and took different actions to prevent hypoglycemia. Severity and frequency of hypoglycemia were compared with respect to how often people worried and took actions to prevent an event. The effect of hypoglycemia on 35 different life activities was quantitatively compared for patients who had and had not experienced a severe hypoglycemic event.Results: At least 95% of respondents agreed that the detailed patient-level descriptions of health states accurately reflected their experience of severe and non-severe, daytime and nocturnal hypoglycemia, thereby validating these descriptions. Respondents who had experienced a severe hypoglycemic event were generally more adversely affected in their worries and actions and life events than those who experienced only non

An evidence-based approach to breastfeeding neonates at risk for hypoglycemia.

Science.gov (United States)

Csont, Georgia Lowmaster; Groth, Susan; Hopkins, Patrick; Guillet, Ronnie

2014-01-01

The revised standard of care for breastfeeding infants at risk of developing hypoglycemia during transitioning to extrauterine life was developed using the American Academy of Pediatrics (AAP) 2011 hypoglycemia guidelines, the Academy of Breastfeeding Medicine protocol, and staff input. A pre/postimplementation chart audit indicated support of infant safety by glucose stabilization, breastfeeding within the first hour of life, and breastfeeding frequency without an increase in blood sampling, formula use, or admissions to the special care nursery. © 2014 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

Diminished epinephrine response to hypoglycemia despite enlarged adrenal medulla in trained rats

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Stallknecht, B; Kjaer, M; Mikines, K J

1990-01-01

/day or served as controls being either sedentary freely eating (C), food restricted (FR), sham swim trained (ST), or cold stressed (CS). Adrenal glands were weighted and cross sectioned for light microscopic determination of size of the adrenal medulla. Endurance-trained compared with control rats had heavier...... adrenal glands (P less than 0.05), higher catecholamine content in the glands (P less than 0.05), and higher adrenal medulla volumes (P less than 0.05) [males: 2.74 +/- 0.16 (T) vs. 2.05 +/- 0.16 (C), 1.90 +/- 0.10 (ST), and 2.21 +/- 0.08 mm3 (CS)] [females: 2.55 +/- 0.11 (T) vs. 1.92 +/- 0.06 mm3 (C......)]. Cold stress or sham swim training did not increase adrenal weight or volume of adrenal medulla (P greater than 0.05). To stimulate adrenal medulla secretion, rats had an insulin-induced hypoglycemia. Insulin dose needed to suppress plasma glucose below 4.0 mM was four times greater in sedentary...

Overnight Glucose Control with Dual- and Single-Hormone Artificial Pancreas in Type 1 Diabetes with Hypoglycemia Unawareness: A Randomized Controlled Trial.

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Abitbol, Alexander; Rabasa-Lhoret, Remi; Messier, Virginie; Legault, Laurent; Smaoui, Mohamad; Cohen, Nathan; Haidar, Ahmad

2018-03-01

The dual-hormone (insulin and glucagon) artificial pancreas may be justifiable in some, but not all, patients. We sought to compare dual- and single-hormone artificial pancreas systems in patients with hypoglycemia unawareness and documented nocturnal hypoglycemia. We conducted a randomized crossover trial comparing the efficacy of dual- and single-hormone artificial pancreas systems in controlling plasma glucose levels over the course of one night's sleep. We recruited 18 adult participants with hypoglycemia unawareness and 17 participants with hypoglycemia awareness, all of whom had documented nocturnal hypoglycemia during 2 weeks of screening. Outcomes were calculated using plasma glucose. In participants with hypoglycemia unawareness, the median (interquartile range [IQR]) percentage of time that plasma glucose was below 4.0 mmol/L was 0% (0-0) on dual-hormone artificial pancreas nights and 0% (0-10) on single-hormone artificial pancreas nights (P = 0.20). Additionally, participants with hypoglycemia unawareness experienced two hypoglycemic events (dual-hormone artificial pancreas nights and three hypoglycemic events on single-hormone artificial pancreas nights. In participants with hypoglycemia awareness, the median (IQR) percentage of time that plasma glucose was below 4.0 mmol/L was 0% (0-0) on both dual- and single-hormone artificial pancreas nights. Hypoglycemia awareness participants experienced zero hypoglycemic events on dual-hormone artificial pancreas nights and one event on single-hormone artificial pancreas nights. In this study, dual-hormone and single-hormone systems performed equally well in preventing nocturnal hypoglycemia in participants with hypoglycemia unawareness. Longer studies over the course of multiple days and nights may be needed to explore possible specific benefits in this population. ClinicalTrials.gov No. NCT02282254.

Potentiation of Hormonal Responses to Hemorrhage and Fasting, but not Hypoglycemia in Conscious Adrenalectomized Rats

Science.gov (United States)

Darlington, Daniel N.; Keil, Lanny C.; Dallman, Mary F.

1989-01-01

Bilateral adrenalectomy (ADRX) in rats removes the source of two major stress-responsive hormones, corticosterone and epinephrine. To test how ADRX rats with-stand stress, we performed the following experiments in adult male rats provided with indwelling femoral arterial and venous cannulae and either ADRX or sham-adrenalectomized (Sham) 3 days later and given 0.5% NaCl to drink. Five to 6 days after adrenal surgery the rats were studied after either a 15 ml/kg.5 min hemorrhage or after an overnight fast followed by insulin-induced hypoglycemia. In fed unstressed ADRX rats, basal mean arterial blood pressure was slightly decreased; heart rate was increased; blood volume, vasopressin, and oxytocin concentrations were not different from sham values; and renin and norepinephrine were significantly elevated. The recovery of arterial pressure after hemorrhage in the ADRX rats was similar to that in the sham group over a 5-h period; however, the responses of vasopressin and oxytocin were significantly greater, and those of renin and norepinephrine were markedly potentiated in the ADRX group. Heart rate recovered faster in the ADRX group and was elevated, compared to the sham value, for most of the 5-h period. Restitution of blood volume was attenuated in the ADRX group, although the restitution of plasma protein was not different between the groups. A significant difference in the change in plasma osmolality between groups after hemorrhage may account for the attenuated restitution of blood volume. After an overnight fast, which reduced blood volume in both groups of rats, the plasma renin concentration rose still further in ADRX rats; the differences in other measured variables observed between fed ADRX and sham groups remained the same. The insulin-induced 50% decrease in glucose caused minor effects on arterial blood pressure and heart rate and occasioned responses in renin and norepinephrine of similar magnitudes in the two groups. We conclude that in the absence of

Disease burden evaluation of fall-related events in the elderly due to hypoglycemia and other diabetic complications: a clinical review

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Malabu UH

2014-08-01

Full Text Available Usman H Malabu,1 Venkat N Vangaveti,1 Richard Lee Kennedy2 1School of Medicine and Dentistry, James Cook University, QLD, Australia; 2Department of Medicine, Deakin University, VIC, Australia Abstract: A hypoglycemia-induced fall is common in older persons with diabetes. The etiology of falls in this population is usually multifactorial, and includes microvascular and macrovascular complications and age-related comorbidities, with hypoglycemia being one of the major precipitating causes. In this review, we systematically searched the literature that was available up to March 31, 2014 from MEDLINE/PubMed, Embase, and Google Scholar using the following terms: hypoglycemia; insulin; diabetic complications; and falls in elderly. Hypoglycemia, defined as blood glucose <4.0 mmol/L (70 mg/dL requiring external assistance, occurs in one-third of elderly diabetics on glucose-lowering therapies. It represents a major barrier to the treatment of diabetes, particularly in the elderly population. Patients who experience hypoglycemia are at a high risk for adverse outcomes, including falls leading to bone fracture, seizures, cognitive dysfunction, and prolonged hospital stays. An increase in mortality has been observed in patients who experience any one of these events. Paradoxically, rational insulin therapy, dosed according to a patient's clinical status and the results of home blood glucose monitoring, so as to achieve and maintain recommended glycemic goals, can be an effective method for the prevention of hypoglycemia and falls in the elderly. Contingencies, such as clinician-directed hypoglycemia treatment protocols that guide the immediate treatment of hypoglycemia, help to limit both the duration and severity of the event. Older diabetic patients with or without underlying renal insufficiency or other severe illnesses represent groups that are at high risk for hypoglycemia-induced falls and, therefore, require lower insulin dosages. In this review

Doege–Potter Syndrome, cause of nonislet cell tumor hypoglycemia: the first case report from Nepal

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Pant V

2017-08-01

Full Text Available Vivek Pant,1 Suman Baral,2 Gita Sayami,3 Prakash Sayami4 1Department of Biochemistry, 2Endocrinology Unit, Department of Medicine, 3Department of Pathology, 4Manmohan Cardiothoracic vascular and transplant Center, Institute of Medicine (IOM, Tribhuvan University Teaching Hospital (TUTH, Kathmandu, Nepal Abstract: Doege–Potter syndrome (DPS, a paraneoplastic syndrome, presents as a hypoinsulinemic hypoglycemia from the ectopic secretion of insulin-like growth factor II from a solitary fibrous tumor which may be intrapleural or extrapleural in origin. We report a case of severe hypoglycemia in a 70-year old female initially admitted for resection of left sided solitary fibrous tumor of pleura. Investigation revealed true hypoglycemia, and DPS was diagnosed. The tumor was completely resected, after which no further hypoglycemic episodes were seen in 2 years follow-up. This is the first case of solitary fibrous tumor of pleura with DPS reported from Nepal. Keywords: insulin-like growth factor II, IGF-II, solitary fibrous tumor, hypoglycemia

Vascular endothelial growth factor during hypoglycemia in patients with type 1 diabetes mellitus: relation to cognitive function and renin-angiotensin system activity

DEFF Research Database (Denmark)

Kristensen, Peter Lommer; Høi-Hansen, Thomas; Boomsma, Frans

2009-01-01

hypoglycemia. High activity in the renin-angiotensin system (RAS) is associated with an increased risk of severe hypoglycemia in patients with type 1 diabetes mellitus. Renin-angiotensin system possibly exerts its mechanism in hypoglycemia via VEGF. We studied the impact of mild hypoglycemia on plasma VEGF...... in patients with type 1 diabetes mellitus and high or low RAS activity and analyzed associations between VEGF levels and cognitive function during hypoglycemia. Eighteen patients with type 1 diabetes mellitus-9 with high and 9 with low RAS activity-underwent a single-blinded, placebo-controlled, crossover...... study with either mild hypoglycemia or stable glycemia. Cognitive function was assessed by the California Cognitive Assessment Package and the Alzheimer Quick Test. Nadir plasma glucose was 2.2 (0.3) mmol/L. During the control study, plasma VEGF did not change. During hypoglycemia, plasma VEGF increased...

Factors associated with an inadequate hypoglycemia in the insulin tolerance test in Japanese patients with suspected or proven hypopituitarism.

Science.gov (United States)

Takahashi, Kiyohiko; Nakamura, Akinobu; Miyoshi, Hideaki; Nomoto, Hiroshi; Kameda, Hiraku; Cho, Kyu Yong; Nagai, So; Shimizu, Chikara; Taguri, Masataka; Terauchi, Yasuo; Atsumi, Tatsuya

2017-04-29

We attempted to identify the predictors of an inadequate hypoglycemia in insulin tolerance test (ITT), defined as a blood glucose level higher than 2.8 mmol/L after insulin injection, in Japanese patients with suspected or proven hypopituitarism. A total of 78 patients who had undergone ITT were divided into adequate and inadequate hypoglycemia groups. The relationships between the subjects' clinical parameters and inadequate hypoglycemia in ITT were analyzed. Stepwise logistic regression analysis identified high systolic blood pressure (SBP) and high homeostasis model assessment of insulin resistance (HOMA-IR) as being independent factors associated with inadequate hypoglycemia in ITT. Receiver operating characteristic (ROC) curve analysis revealed the cutoff value for inadequate hypoglycemia was 109 mmHg for SBP and 1.4 for HOMA-IR. The areas under ROC curve for SBP and HOMA-IR were 0.72 and 0.86, respectively. We confirmed that high values of SBP and HOMA-IR were associated with inadequate hypoglycemia in ITT, regardless of the degree of reduction of pituitary hormone levels. Furthermore, the strongest predictor of inadequate hypoglycemia was obtained by using the cutoff value of HOMA-IR. Our results suggest that HOMA-IR is a useful pre-screening tool for ITT in these populations.

Radish juice and corn oil as adjuvants that decrease the destructive alterations in hypoglycemia rats subjected to gamma irradiation

International Nuclear Information System (INIS)

Hanafy, N.

2007-01-01

This study was performed to investigate the decrease in different biochemical and histopathological alterations that may occur following the oral administration of aqueous extract of radish at the dose level (50 mg/100 g body weight) and the addition of 10% corn oil to the diet of hypoglycemia rats and /or exposed to 6 Gy of gamma radiation. The experiment included normal male albino rats and hypoglycemia ones.The hypoglycemia rats divided into tow groups; the first group was treated with radish juice or radish juice with diet containing corn oil and the other group was hypoglycemia rats exposed to 6 Gy of gamma radiation then treated also with radish juice or radish juice with diet containing 10% corn oil. Biochemical analysis included levels of blood sugar, total lipids, cholesterol, total protein and albumin, in addition to the activity of AST and ALT were evaluated. The level of TBARs and the histopathological changes in liver and kidney were also investigated. Treatment of irradiated hypoglycemia rats with radish juice either alone or combined with a diet containing 10% corn oil reverse the serum fasting glucose level nearly to the control level. Amelioration in lipid profile was recorded after the treatment of the hypoglycemia rats or those hypoglycemia irradiated then treated with radish juice and fed on a diet containing 10% corn oil. Also, significant amelioration was occurred in liver transaminases, total proteins, albumin and creatinine levels as compared to those of hypoglycemia group. TBARs levels showed remarkable decrease in liver and kidney tissues in comparison with control and hypoglycemia rats and/or gamma irradiated levels when it is treated with radish juice and diet containing corn oil. Also, the histopathological changes of the same tissues revealed the same trend. From the different observations , it is possible to conclude that treatment of rats with radish juice in addition to feeding on diet containing 10% corn oil could reduce the

The role of hypoglycemia in the burden of living with diabetes among adults with diabetes and family members

DEFF Research Database (Denmark)

Nefs, Giesje; Pouwer, François

2018-01-01

-severe hypoglycemia in the past year (OR = 2.45, 1.25-4.83), self-reported severe hypoglycemia in the past year (OR = 1.91, 1.02-3.58), and being very worried about hypoglycemia at least occasionally (OR = 3.64, 2.18-6.10). For family members, the odds of experiencing living with diabetes as a burden was increased......, 412 Dutch adults with type 1 or type 2 diabetes and 86 family members completed questions about the burden of living with diabetes, the frequency of hypoglycemia, worries about these events, and several demographic and clinical factors. Analyses included hierarchical logistic regression. RESULTS...

Prevalence of nocturnal hypoglycemia in first trimester of pregnancy in patients with insulin treated diabetes mellitus

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Hellmuth, Ellinor Adelheid; Damm, P; Mølsted-Pedersen, L

2000-01-01

BACKGROUND: Excellent metabolic control before conception and during diabetic pregnancies is the aim in order to avoid malformations and perinatal morbidity. Since an inverse correlation between median blood glucose concentration (BG) and hypoglycemia as well as a high prevalence of nocturnal...... the night, caused by either discomfort or cannula problems. Of the remaining 43 patients, 16 (37%) had at least one blood glucose ... of pregnancy in insulin treated patients. Only one patient registered the hypoglycemia. Nocturnal hypoglycemia could be predicted in the majority of patients by measurements of BG before bedtime....

Association of insulin-like growth factor-1 with glycemic control and occurrence of severe hypoglycemia in patients with type 1 diabetes mellitus

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Færch, Louise; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2012-01-01

GH is implicated in the counter-regulatory response to hypoglycemia. We tested whether IGF1 levels are associated with occurrence of severe hypoglycemic events in patients with type 1 diabetes and whether the IGF1 concentration is influenced by glycemic control....

Hypoglycemia in small for gestational age neonates based on gestational age, gender, birth weight and mode of delivery

International Nuclear Information System (INIS)

Ramzan, M.; Razzaq, A.; Kiyani, A.N.

2017-01-01

To determine the frequency of hypoglycemia in small for gestational age neonates based on gestational age, gender, birth weight and mode of delivery. Study Design: Cross sectional study. Place and Duration of Study: Neonatal Intensive Care Unit (NICU), Military Hospital Rawalpindi, from Dec 2011 to Jul 2012. Material and Methods: We included 383 small for gestational age (SGA) neonates admitted in NICU. Blood glucose levels were checked in all neonates. Variables included in study were gestational age, gender, birth weight and mode of delivery. Results: Out of 383 SGA neonates enrolled by non-probability consecutive sampling, 191 (49.87%) were males and 192 (50.13%) were females. Out of these 203 (53%) were preterm, 165 (43.08%) were delivered at term and 15 (3.92%) were post-term SGA neonates with mean gestational age of 34 weeks 5 days. Out of the total 383 SGA neonates 208 (54.31%) developed hypoglycemia during stay in NICU and 175 (45.69%) remained euglycemic. Extremely low birth weight (ELBW) neonates were at highest risk to develop hypoglycemia (82.35%). It was seen that SGA neonates delivered by instrumental vaginal delivery had highest risk of developing hypoglycemia i.e. 20 (76.92) out of 26 neonates. Out of 103 vaginal deliveries 41 (39.81%) had hypoglycemia and out of 254 Caesarean section 147 (57.87%) had hypoglycemia. Conclusion: Low birth weight neonates delivered by instrumental vaginal delivery were found to be at a higher risk of developing hypoglycemia. (author)

Factors associated with hypoglycemia episodes in hospitalized type ...

African Journals Online (AJOL)

Purpose: To determine the factors associated with severity of hypoglycemia in hospitalized type 2 diabetes mellitus patients in a tertiary health facility in Malaysia. Methods: This retrospective study involved 207 hospitalised T2DM patients with hypoglycaemia episodes from January 2008 to December 2012 and was ...

Review of insulin-associated hypoglycemia and its impact on the management of diabetes in Southeast Asian countries.

Science.gov (United States)

Goh, Su-Yen; Hussein, Zanariah; Rudijanto, Achmad

2017-09-01

Although the incidence of diabetes is rising in Southeast Asia, there is limited information regarding the incidence and manifestation of insulin-associated hypoglycemia. The aim of the present review was to discuss what is currently known regarding insulin-associated hypoglycemia in Southeast Asia, including its known incidence and impact in the region, and how the Southeast Asian population with diabetes differs from other populations. We found a paucity of data regarding the incidence of hypoglycemia in Southeast Asia, which has contributed to the adoption of Western guidelines. This might not be appropriate, as Southeast Asians have a range of etiological, educational and cultural differences from Western populations with diabetes that might place them at greater risk of hypoglycemia if not managed optimally. For example, Southeast Asians with type 2 diabetes tend to be younger, with lower body mass indexes than their Western counterparts, and the management of type 2 diabetes with premixed insulin preparations is more common in Southeast Asia. Both of these factors might result in higher rates of hypoglycemia. In addition, Southeast Asians are often poorly educated about hypoglycemia and its management, including during Ramadan fasting. We conclude there is a need for more information about Southeast Asian populations with diabetes to assist with the construction of more appropriate national and regional guidelines for the management of hypoglycemia, more closely aligned to patient demographics, behaviors and treatment practices. Such bespoke guidelines might result in a greater degree of implementation and adherence within clinical practice in Southeast Asian nations. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Hypoglycemia, S-ACE and ACE genotypes in a Danish nationwide population of children and adolescents with type 1 diabetes

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Johannesen, Jesper; Svensson, Jannet; Bergholdt, Regine

2011-01-01

OBJECTIVE: High S-ACE levels have been shown to predispose to increased risk of hypoglycemia, however; some inconsistency relates to the risk of the ACE genotype. We investigated the association between S-ACE level at diagnosis and ACE genotype to long-term risk of severe hypoglycemia in more than...... to increased risk of hypoglycemia generated from a negative binominal model were long diabetes duration (p high S-ACE level (p = 0.0497) when adjusted for ACE genotype. In the stratified analysis, S-ACE and insulin dosage were associated with hypoglycemia in girls (p = 0.026 and 0...

What Happens to Blood Glucose Concentrations After Oral Treatment for Neonatal Hypoglycemia?

Science.gov (United States)

Harris, Deborah L; Gamble, Greg D; Weston, Philip J; Harding, Jane E

2017-11-01

To determine the change in blood glucose concentration after oral treatment of infants with hypoglycemia in the first 48 hours after birth. We analyzed data from 227 infants with hypoglycemia (blood glucose dextrose or placebo gel plus feeding with formula, expressed breast milk, or breast feeding. The overall mean increase in blood glucose concentration was 11.7 mg/dL (95% CI 10.4-12.8). The increase was greater after buccal dextrose gel than after placebo gel (+3.0 mg/dL; 95% CI 0.7-5.3; P = .01) and greater after infant formula than after other feedings (+3.8 mg/dL; 95% CI 0.8-6.7; P = .01). The increase in blood glucose concentration was not affected by breast feeding (+2.0 mg/dL; 95% CI -0.3 to 44.2; P = .09) or expressed breast milk (-1.4 mg/dL; 95% CI -3.7 to 0.9; P = .25). However, breast feeding was associated with reduced requirement for repeat gel treatment (OR = 0.52; 95% CI 0.28-0.94; P = .03). Treatment of infants with hypoglycemia with dextrose gel or formula is associated with increased blood glucose concentration and breast feeding with reduced need for further treatment. Dextrose gel and breast feeding should be considered for first-line oral treatment of infants with hypoglycemia. Copyright © 2017 Elsevier Inc. All rights reserved.

Apparent mineral retention is similar in control and hyperinsulinemic men after consumption of high amylose cornstarch.

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Behall, Kay M; Howe, Juliette C; Anderson, Richard A

2002-07-01

The effects on apparent mineral retention after long-term consumption of a high amylose diet containing 30 g resistant starch (RS) were investigated in 10 control and 14 hyperinsulinemic men. Subjects consumed products (bread, muffins, cookies, corn flakes and cheese puffs) made with standard (70% amylopectin, 30% amylose; AP) or high amylose (70% amylose, 30% amylopectin; AM) cornstarch for two 14-wk periods in a crossover pattern. Starch products replaced usual starches in the habitual diet for 10 wk followed by 4 wk of consuming the controlled diets. During wk 12, all urine, feces and duplicate foods were collected for 7 d. Urinary chromium losses after a glucose tolerance test or 24-h collections of the hyperinsulinemic and control subjects did not differ and were not altered by diet. Except for zinc, the two subject types did not differ significantly in apparent mineral balance. Apparent retentions of calcium and magnesium were not significantly affected by diet (AM vs. AP) or type-by-diet interaction. Apparent iron retention tended to be greater after AM than AP consumption (P copper retention was greater after consuming AP than after AM (P < 0.02), whereas apparent zinc retention was greater after consuming AM than after AP (P < 0.018). Zinc also showed a significant type-by-diet interaction (P < 0.034) with control subjects retaining less zinc after consuming AP than after AM. In summary, a high amylose cornstarch diet containing 30 g RS could be consumed long term without markedly affecting, and possibly enhancing, retention of some minerals.

ACUTE HYPOGLYCEMIA RESULTS IN REDUCED CORTICAL NEURONAL INJURY IN THE DEVELOPING IUGR RAT

OpenAIRE

Maliszewski-Hall, Anne M.; Stein, Ariel B.; Alexander, Michelle; Ennis, Kathleen; Rao, Raghavendra

2015-01-01

Background Hypoglycemia (HG) is common in IUGR neonates. In normally grown (NG) neonatal rats, acute HG causes neuronal injury in the brain, cerebral cortex more vulnerable than the hippocampus (HPC). We hypothesized that the IUGR brain is less vulnerable to hypoglycemia-induced injury while preserving the regional variation in vulnerability. Methods We induced IUGR via bilateral uterine artery ligation on gestational day 19 (term 22d) rats. On postnatal day 14, insulin-induced HG of equivale...

Islet Transplantation Provides Superior Glycemic Control With Less Hypoglycemia Compared With Continuous Subcutaneous Insulin Infusion or Multiple Daily Insulin Injections.

Science.gov (United States)

Holmes-Walker, Deborah Jane; Gunton, Jenny E; Hawthorne, Wayne; Payk, Marlene; Anderson, Patricia; Donath, Susan; Loudovaris, Tom; Ward, Glenn M; Kay, Thomas Wh; OʼConnell, Philip J

2017-06-01

The aim was to compare efficacy of multiple daily injections (MDI), continuous subcutaneous insulin infusion (CSII) and islet transplantation to reduce hypoglycemia and glycemic variability in type 1 diabetes subjects with severe hypoglycemia. This was a within-subject, paired comparison of MDI and CSII and CSII with 12 months postislet transplantation in 10 type 1 diabetes subjects referred with severe hypoglycemia, suitable for islet transplantation. Individuals were assessed with HbA1c, Edmonton Hypoglycemia Score (HYPOscore), continuous glucose monitoring (CGM) and in 8 subjects measurements of glucose variability using standard deviation of glucose (SD glucose) from CGM and continuous overlapping net glycemic action using a 4 hour interval (CONGA4). After changing from MDI to CSII before transplantation, 10 subjects reduced median HYPOscore from 2028 to 1085 (P transplantation, there were significant reductions in all baseline parameters versus CSII, respectively, HbA1c (6.4% cf 8.2%), median HYPOscore (0 cf 1085), mean glucose (7.1 cf 8.6 mmol L), SD glucose (1.7 cf 3.2 mmol/L), and CONGA4 (1.6 cf 3.0). In subjects with severe hypoglycemia suitable for islet transplantation, CSII decreased hypoglycemia frequency and glycemic variability compared with MDI whereas islet transplantation resolved hypoglycemia and further improved glycemic variability regardless of insulin independence.

Incidence and risk factors for severe and symptomatic hypoglycemia in type 1 diabetes. Results of the HYPOS-1 study.

Science.gov (United States)

Giorda, Carlo B; Ozzello, Alessandro; Gentile, Sandro; Aglialoro, Alberto; Chiambretti, Anna; Baccetti, Fabio; Gentile, Francesco M; Lucisano, Giuseppe; Nicolucci, Antonio; Rossi, Maria Chiara

2015-10-01

Hypoglycemia is common in type 1 diabetes mellitus (T1DM). We aimed to update the incidence of severe and symptomatic hypoglycemia and investigate several correlated factors. In this multicenter, observational retrospective study, the data of 206 T1DM patients from a sample of 2,229 consecutive patients seen at 18 diabetes clinics were analyzed. Sociodemographic and clinical characteristics, severe hypoglycemia in the past 12 months, and symptomatic hypoglycemia in the past 4 weeks were recorded with a self-report questionnaire and a clinical form during a routine visit. Poisson multivariate models were applied. A minority of patients accounted for the majority of both severe and symptomatic episodes. The incidence rate (IR) of severe hypoglycemia was 0.49 (0.40-0.60) events/person-years. The incidence rate ratio (IRR) was higher in patients with previous severe hypoglycemia (3.71; 2.28-6.04), neuropathy (4.16; 2.14-8.05), long duration (>20 years, 2.96; 1.60-5.45), and on polypharmacy (1.24; 1.13-1.36), but it was lower when a complication was present. The IR of symptomatic hypoglycemia was 53.3 events/person-years, with an IRR significantly higher among women or patients with better education, or shorter duration or on pumps. The IRR was lower in patients with higher BMI or neuropathy or aged more than 50 years. Fewer than 20 % of T1DM patients are free from hypoglycemia, with one in six having experienced at least one severe episode in the last year. The distribution is uneven, with a tendency of episodes to cluster in some patients. Severe and symptomatic episodes have different correlates and reflect different conditions.

Profound neonatal hypoglycemia and lactic acidosis caused by pyridoxine-dependent epilepsy.

Science.gov (United States)

Mercimek-Mahmutoglu, Saadet; Horvath, Gabriella A; Coulter-Mackie, Marion; Nelson, Tanya; Waters, Paula J; Sargent, Michael; Struys, Eduard; Jakobs, Cornelis; Stockler-Ipsiroglu, Sylvia; Connolly, Mary B

2012-05-01

Pyridoxine-dependent epilepsy (PDE) was first described in 1954. The ALDH7A1 gene mutations resulting in α-aminoadipic semialdehyde dehydrogenase deficiency as a cause of PDE was identified only in 2005. Neonatal epileptic encephalopathy is the presenting feature in >50% of patients with classic PDE. We report the case of a 13-month-old girl with profound neonatal hypoglycemia (0.6 mmol/L; reference range >2.4), lactic acidosis (11 mmol/L; reference range A (p.Val278Val), and a novel putative pathogenic missense mutation c.1192G>C (p.Gly398Arg) in the ALDH7A1 gene. She has been seizure-free since 1.5 months of age on treatment with pyridoxine alone. She has motor delay and central hypotonia but normal language and social development at the age of 13 months. This case is the first description of a patient with PDE due to mutations in the ALDH7A1 gene who presented with profound neonatal hypoglycemia and lactic acidosis masquerading as a neonatal-onset gluconeogenesis defect. PDE should be included in the differential diagnosis of hypoglycemia and lactic acidosis in addition to medically refractory neonatal seizures.

Hypoglycemia and Medical Expenses in Patients with Type 2 Diabetes Mellitus: An Analysis Based on the Korea National Diabetes Program Cohort.

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Sang Youl Rhee

Full Text Available Hypoglycemia is one of the most important adverse events in individuals with type 2 diabetes mellitus (T2DM. However, hypoglycemia-related events are usually overlooked and have been documented less in clinical practice.We evaluated the incidence, clinical characteristics, and medical expenses of hypoglycemia related events in T2DM patients based on the Korea National Diabetes Program (KNDP, which is the largest multi-center, prospective cohort in Korea (n = 4,350. For accurate outcomes, the KNDP data were merged with claims data from the Health Insurance Review and Assessment Service (HIRA of Korea.During a median follow-up period of 3.23 years (95% CI: 3.14, 3.19, 88 subjects (2.02% were newly diagnosed with hypoglycemia, and the incidence of hypoglycemia was 6.44 cases per 1,000 person-years (PY. Individuals with hypoglycemia were significantly older (59.7±10.7 vs. 53.3±10.4 years, p < 0.001, had more hospital visits (121.94±126.88 days/PY, p < 0.001, had a longer hospital stays (16.13±29.21 days/PY, p < 0.001, and incurred greater medical costs ($2,447.56±4,056.38 vs. $1,336.37±3,403.39 /PY, p < 0.001 than subjects without hypoglycemia.Hypoglycemia-related events were infrequently identified among the medical records of T2DM subjects. However, they were associated significantly with poor clinical outcomes, and thus, hypoglycemia could have a substantial burden on the Korean national healthcare system.

Roux en Y gastric bypass hypoglycemia resolves with gastric feeding or reversal: Confirming a non-pancreatic etiology

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Dawn Belt Davis

2018-03-01

Full Text Available Objective: Postprandial hypoglycemia is an infrequent but disabling complication of Roux-en-Y gastric bypass (RYGB surgery. Controversy still exists as to whether the postprandial hyperinsulinemia observed is due to inherent changes in pancreatic β-cell mass or function or to reversible alterations caused by RYGB anatomy. We aimed to determine if gastric feeding or reversal of RYGB would normalize postprandial glucose and hormone excursions in patients with symptomatic hypoglycemia. Methods: We completed a prospective study of six patients with severe symptomatic RYGB hypoglycemia who underwent RYGB reversal. An additional subject without hypoglycemia who underwent RYGB reversal was also studied prospectively. Mixed meal tolerance testing (MTT was done orally (RYGB anatomy, via gastrostomy tube in the excluded stomach in the setting of RYGB, and several months after RYGB reversal. Results: All subjects reported symptomatic improvement of hypoglycemia after reversal of RYGB. Weight gain after reversal was moderate and variable. Postprandial glucose, insulin, and GLP-1 excursions were significantly diminished with gastric feeding and after reversal. Insulin secretion changed proportional to glucose levels and insulin clearance increased after reversal. Glucagon/insulin ratios were similar throughout study. We further compared the impact of modified sleeve gastrectomy reversal surgery to those with restoration of complete stomach and found no significant differences in weight regain or in postprandial glucose or hormone levels. Conclusions: Reversal of RYGB is an effective treatment option for severe postprandial hypoglycemia. The pathophysiology of this disorder is primarily due to RYGB anatomy resulting in altered glucose, gut, and pancreatic hormone levels and decreased insulin clearance, rather than inherent β-cell hyperplasia or hyperfunction. Keywords: Hypoglycemia, Insulin, Glucagon-like peptide 1, Roux en Y gastric bypass, Gastric bypass

Nocturnal hypoglycemia identified by a continuous glucose monitoring system in patients with primary adrenal insufficiency (Addison's Disease).

Science.gov (United States)

Meyer, Gesine; Hackemann, Annika; Reusch, Juergen; Badenhoop, Klaus

2012-05-01

Hypoglycemia can be a symptom in patients with Addison's disease. The common regimen of replacement therapy with oral glucocorticoids results in unphysiological low cortisol levels in the early morning, the time of highest insulin sensitivity. Therefore patients with Addison's disease are at risk for unrecognized and potentially severe nocturnal hypoglycemia also because of a disturbed counterregulatory function. Use of a continuous glucose monitoring system (CGMS) could help to adjust hydrocortisone treatment and to avoid nocturnal hypoglycemia in these patients. Thirteen patients with Addison's disease were screened for hypoglycemia wearing a CGMS for 3-5 days. In one patient we identified a hypoglycemic episode at 3:45 a.m. with a blood glucose level of 46 mg/dL, clearly beneath the 95% tolerance interval of minimal glucose levels between 2 and 4 a.m. (53.84 mg/dL). After the hydrocortisone replacement scheme was changed, the minimum blood glucose level between 2 and 4 a.m. normalized to 87 mg/dL. Continuous glucose monitoring can detect nocturnal hypoglycemia in patients with primary adrenal insufficiency and hence prevent in these patients an impaired quality of life and even serious adverse effects.

Hypoglycemia perception: Cross-cultural differences in Punjabi and Hindi speaking postmenopausal women.

Science.gov (United States)

Bhutani, Jaikrit; Kalra, Sanjay; Bhutani, Sukriti; Kalra, Bharti

2013-10-01

The cross cultural differences in perception of menopausal symptoms are well known and these differences in perception of hypoglycemic symptoms in Russian-speaking and Caucasian postmenopausal women have been reported. This study assessed cross - linguistic and cross - cultural differences in symptomatology of self reported hypoglycemia, between Punjabi and Hindi speaking diabetic post menopausal women. Thirty Punjabi speaking and 20 Hindi speaking diabetic postmenopausal women aged over 50 years, were recruited for this study. Each subject was asked, what happens to you when you have low sugar? in the language of her choice, and spontaneous answers were recorded verbatim. The data so obtained was analyzed by paper and pen method to obtain an understanding of the frequency of self reporting of various symptoms and then analyzed using Statistical Package for Social Science ver.19.0. Symptoms of hollowness, cold sweats and headache correlated significantly (P Punjabi speaking cohort were bilingual. Some symptoms of hypoglycemia may have been missed or over-reported by participants. Diabetes care professionals should be aware that persons with diabetes from varying linguistic backgrounds may report symptoms of hypoglycemia differently.

[Spontaneous hypoglycemia].

Science.gov (United States)

Ellorhaoui, M; Schultze, W

1977-01-15

On the basis of a survey is attempted to describe mode of development, symptomatology, individual forms and the different possibilities of therapy of the spontaneous hypoglycaemias. A particularly broad range was devoted to the cerebral sequelae, since in these cases--according to our experience--on account of simulation of neurologico-psychiatric symptoms at the soonest wrong diagnoses are to be expected. Furthermore, it is attempted to classify the hypoglycemias according to their development, in which cases their incompleteness was evident from the very beginning. The individual forms of appearance are treated according their to significance. Out of the inducible hypoglycaemias a particular attention is devoted to the forms caused by insulin and oral antidiabetics, since these most frequently participate in the development. Finally the author inquires into diagnostic measures for recognition of special forms of hypoglycaemia. In this place the diagnostics of hyperinsulinism conditioned by adenomatosis or tumours of other kinds is of particular importance. Finally conservative and operative possibilities of the therapy of these tumours are discussed,whereby the only recently tested treatment with streptotocin is mentioned.

A social media intervention to improve hypoglycemia management at a multicenter hospital: a quality improvement pilot for clinical nurses.

Science.gov (United States)

De Sousa, Filomena; Jackson, Jennifer; Knight, Ruth; Cloutier, Edith; Basa, Rosemary; Fourney, Anne; Devecseri, Kathleen

2018-02-01

Hypoglycemia poses significant risk to inpatients. Nursing management of hypoglycemia is a challenge, despite established best practice guidelines. Social media is an effective tool for sharing information and could overcome barriers to clinical education at a multicenter hospital. The purpose of this quality improvement intervention was to create and disseminate social media posts about best practices in hypoglycemia management. An unmatched pre-and post-survey assessed nursing knowledge of hypoglycemia management. Social media posts were created to visually outline the steps for hypoglycemia management over 2 weeks, across a nursing social media platform. We assessed the reach of the posts via Facebook and a survey. The posts reached 2962 users during the first week, and 1491 users the second week. A social media intervention can have a substantial reach and distribute information across a multicenter hospital. Additional study is needed to determine what factors could support an increase in nursing knowledge through a social media campaign.

The unexpected truth about dates and hypoglycemia

Directory of Open Access Journals (Sweden)

Mohammed I Yasawy

2016-01-01

Full Text Available Background: Dates are a concentrated source of essential nutrients, vitamins, minerals, and carbohydrates (CHOs, which are necessary for the maintenance of optimum health. Most of the CHOs in dates come from sugars including glucose and fructose. Dates are commonly consumed in Saudi Arabia, particularly at the time of breaking the fast to provide instant energy and maintain blood sugar level. However, dates may cause hypoglycemia in a rare condition named as heredity fructose intolerance (HFI, and a few families have been to see us with a history of that nature. This is to report the preliminary results of an on-going study of a group of patients who get symptoms of hypoglycemia following the ingestion of dates and have suffered for years without an accurate diagnosis. Methodology: This report is based on three patients, from the same family, living in a date growing region of the Kingdom of Saudi Arabia (KSA. The patients had been to several medical centers without getting any definite answers or diagnosis until they were referred to the Gastroenterology Clinic of King Fahd Hospital of the University, Al-Khobar, KSA. The data were obtained by careful history and laboratory investigations, and a final diagnosis of HFI made on fructose intolerance test (FIT. Results: The patients reported that they had avoided eating dates because of various symptoms, such as bloating, nausea, and even hypoglycemia when larger amounts were consumed. Their other symptoms included sleepiness, sweating, and shivering. After full examinations and necessary laboratory tests based on the above symptoms, FIT was performed and the patients were diagnosed with HFI. They were referred to a dietitian who advised a fructose-free diet. They felt well and were free of symptoms. Conclusion: HFI may remain undiagnosed until adulthood and may lead to disastrous complications and even death. The diagnosis can only be suspected after a careful dietary history is taken supported by

HEART FAILURE, DIABETES, BETA-BLOCKERS AND RISK OF HYPOGLYCEMIA

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A. A. Aleksandrov

2008-01-01

Full Text Available Aim. To evaluate an influence of carvedilol on risk of hypoglycemia in patients with diabetes type 2 (D2 and chronic heart failure (CHF treated with angiotensin converting enzyme (ACE inhibitors.Material and methods. 13 patients (10 men, 3 women; aged 59,8±6,7 y.o. with D2 and CHF caused by ischemic heart disease were included in the study. Before inclusion all patients were treated with ACE inhibitors and various beta-blockers (atenolol, metoprolol, bisoprolol. These beta-blockers were changed for carvedilol. Heart ultrasonography, blood pressure control, glycemia monitoring, HbA1c level determination were performed before, during and after carvedilol therapy.Results. Carvedilol reduces frequency and duration of hypoglycaemia episodes. There were not episodes of severe hypoglycaemia during carvedilol therapy.Conclusion. Carvedilol reduces risk of hypoglycemia when it is used in combination with ACE inhiditors in diabetic patients with CHF.

Knowledge of hypoglycemia and its associated factors among type 2 diabetes mellitus patients in a Tertiary Care Hospital in South India.

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Shriraam, Vanishree; Mahadevan, Shriraam; Anitharani, M; Jagadeesh, Nalini Sirala; Kurup, Sreelekha Bhaskara; Vidya, T A; Seshadri, Krishna G

2015-01-01

Hypoglycemia being the rate limiting complication in the attainment of strict glycemic control in diabetes management, in this study, we intended to study the knowledge of its symptoms, target blood levels during treatment and ways of prevention among type 2 diabetes patients attending Outpatient Department (OPD) of a medical college hospital. Every fifth patient attending the OPD during the 4 months between March and June 2013 was interviewed using a questionnaire. The study included 366 type 2 diabetic patients, of which 76.5% were females. The target fasting and postprandial blood glucose levels while on treatment was known to 135 (36.9%) and 126 (34.4%) patients, respectively. The common symptoms of hypoglycemia known to the study subjects were dizziness (81.4%), weakness (73.8%), and drowsiness (72.1%). Overall, 242 (66.1%) diabetic patients had good knowledge on hypoglycemia (knowledge of at least three symptoms of hypoglycemia together with at least one precipitating factor and at least one remedial measure). Higher age, illiteracy, low socioeconomic status were associated with poor knowledge whereas treatment with insulin along with oral hypoglycemic agents was associated with good knowledge on hypoglycemia. Sex and duration of disease were not associated with knowledge on hypoglycemia. Although the knowledge on symptoms of hypoglycemia, precipitating factors, remedial measures are high in this study, the target blood levels, complications were known to just a third of them. There is a knowledge gap on important aspects of hypoglycemia among type 2 diabetic patients.

A randomized trial of a home system to reduce nocturnal hypoglycemia in type 1 diabetes.

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Maahs, David M; Calhoun, Peter; Buckingham, Bruce A; Chase, H Peter; Hramiak, Irene; Lum, John; Cameron, Fraser; Bequette, B Wayne; Aye, Tandy; Paul, Terri; Slover, Robert; Wadwa, R Paul; Wilson, Darrell M; Kollman, Craig; Beck, Roy W

2014-07-01

Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels. Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred. Overnight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43-0.64]; P 2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P 250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm. Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis. © 2014 by the American Diabetes Association.

Knowledge of hypoglycemia and its associated factors among type 2 diabetes mellitus patients in a Tertiary Care Hospital in South India

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Vanishree Shriraam

2015-01-01

Full Text Available Introduction: Hypoglycemia being the rate limiting complication in the attainment of strict glycemic control in diabetes management, in this study, we intended to study the knowledge of its symptoms, target blood levels during treatment and ways of prevention among type 2 diabetes patients attending Outpatient Department (OPD of a medical college hospital. Materials and Methods: Every fifth patient attending the OPD during the 4 months between March and June 2013 was interviewed using a questionnaire. Results: The study included 366 type 2 diabetic patients, of which 76.5% were females. The target fasting and postprandial blood glucose levels while on treatment was known to 135 (36.9% and 126 (34.4% patients, respectively. The common symptoms of hypoglycemia known to the study subjects were dizziness (81.4%, weakness (73.8%, and drowsiness (72.1%. Overall, 242 (66.1% diabetic patients had good knowledge on hypoglycemia (knowledge of at least three symptoms of hypoglycemia together with at least one precipitating factor and at least one remedial measure. Higher age, illiteracy, low socioeconomic status were associated with poor knowledge whereas treatment with insulin along with oral hypoglycemic agents was associated with good knowledge on hypoglycemia. Sex and duration of disease were not associated with knowledge on hypoglycemia. Conclusion: Although the knowledge on symptoms of hypoglycemia, precipitating factors, remedial measures are high in this study, the target blood levels, complications were known to just a third of them. There is a knowledge gap on important aspects of hypoglycemia among type 2 diabetic patients.

Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society.

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Seaquist, Elizabeth R; Anderson, John; Childs, Belinda; Cryer, Philip; Dagogo-Jack, Samuel; Fish, Lisa; Heller, Simon R; Rodriguez, Henry; Rosenzweig, James; Vigersky, Robert

2013-05-01

To review the evidence about the impact of hypoglycemia on patients with diabetes that has become available since the past reviews of this subject by the American Diabetes Association and The Endocrine Society and to provide guidance about how this new information should be incorporated into clinical practice. Five members of the American Diabetes Association and five members of The Endocrine Society with expertise in different aspects of hypoglycemia were invited by the Chair, who is a member of both, to participate in a planning conference call and a 2-day meeting that was also attended by staff from both organizations. Subsequent communications took place via e-mail and phone calls. The writing group consisted of those invitees who participated in the writing of the manuscript. The workgroup meeting was supported by educational grants to the American Diabetes Association from Lilly USA, LLC and Novo Nordisk and sponsorship to the American Diabetes Association from Sanofi. The sponsors had no input into the development of or content of the report. The writing group considered data from recent clinical trials and other studies to update the prior workgroup report. Unpublished data were not used. Expert opinion was used to develop some conclusions. Consensus was achieved by group discussion during conference calls and face-to-face meetings, as well as by iterative revisions of the written document. The document was reviewed and approved by the American Diabetes Association's Professional Practice Committee in October 2012 and approved by the Executive Committee of the Board of Directors in November 2012 and was reviewed and approved by The Endocrine Society's Clinical Affairs Core Committee in October 2012 and by Council in November 2012. The workgroup reconfirmed the previous definitions of hypoglycemia in diabetes, reviewed the implications of hypoglycemia on both short- and long-term outcomes, considered the implications of hypoglycemia on treatment outcomes

Patologia molecular do receptor de sulfoniluréia (SUR1)

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Reis, André F.; Velho, Gilberto

2000-01-01

The sulfonylurea receptor is a subunit of the ATP-sensitive potassium channel, which is expressed in the pancreatic beta cell. The central role of this receptor in glucose-induced insulin secretion was confirmed by description that mutations in this gene might result in hyperinsulinemic hypoglycemia of infancy. The possible role of SUR1 gene variants in the genetic susceptibility for type 2 diabetes mellitus has been studied. In this review, we discuss the results concerning the genetic varia...

Neonatal episodic hypoglycemia: a finding of valproic acid withdrawal.

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Çoban, Dilek; Kurtoğlu, Selim; Akın, Mustafa Ali; Akçakuş, Mustafa; Güneş, Tamer

2010-01-01

The treatment of epilepsy during pregnancy is a worldwide problem. Drugs need to be used to control seizures in the mothers. In utero, exposure to valproic acid (VPA) and phenytoin (PH) may cause congenital malformations and also withdrawal symptoms such as irritability, jitteriness and symptoms of hypoglycemia. We present here a newborn with episodic hypoglycemia due to in utero exposure to VPA and PH. The mother was diagnosed as having complex partial epilepsy and was treated with PH (200 mg/day) and VPA (600 mg/day). The offspring developed jitteriness on the second day of life. The infant was hypoglycemic (32 mg/dl). These findings were accepted as withdrawal symptoms, since serum levels of VPA and PH were 37.8 μg/ml (50-100 μg/ml) and 6.37 μg/dl (10-20 μg/ml), respectively. Measurement of blood glucose is important and should be carefully monitored in infants exposed to antiepileptics in utero.

Hypoglycemia-Induced Decrease of EEG Coherence in Patients with Type 1 Diabetes

DEFF Research Database (Denmark)

Rubega, Maria; Sparacino, Giovanni; Sejling, A. S.

2016-01-01

investigated. The aim of the present work is to use a coherence approach to quantitatively assess how hypoglycemia affects mutual connectivity of different brain areas. MATERIALS AND METHODS: EEG multichannel data were obtained from 19 patients with T1D (58% males; mean age, 55 ± 2.4 years; diabetes duration......: In passing from eu- to hypoglycemia, absolute values of the iPDC function tend to decrease in both bands in all combinations of the considered channels. In particular, the scalar indicator [Formula: see text], which summarizes iPDC information, significantly decreased (P ...-A1A2 to C3-A1A2 from O1-A1A2 to C4-A1A2 and from O2-A1A2 to Cz-A1A2 in the theta band and from O1-A1A2 to T4-A1A2 and from O1-A1A2 to C4-A1A2 in the alpha band. CONCLUSIONS: The coherence decrease measured by iPDC in passing from eu- to hypoglycemia is likely related to the progressive loss...

Long term prognosis of symptomatic occipital lobe epilepsy secondary to neonatal hypoglycemia.

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Montassir, Hesham; Maegaki, Yoshihiro; Ohno, Kousaku; Ogura, Kaeko

2010-02-01

To report on long-term clinical course in patients with symptomatic occipital lobe epilepsy secondary to neonatal hypoglycemia. Six patients with neonatal hypoglycemia and symptomatic occipital lobe epilepsy were studied in our hospital through reviewing their medical records retrospectively. The median onset age of epilepsy was 2 years 8 months and median follow-up period was 12 years and 4 months. Initial seizure types were generalized convulsions in 4 patients, hemiconvulsion in 1, and infantile spasms in 1. Ictal manifestations of main seizures were identical to occipital lobe seizures, such as eye deviation, eye blinking, ictal vomiting, and visual hallucination. Seizure frequency was maximum during infancy and early childhood and decreased thereafter with no seizure in 2 patients, a few seizures a year in 3, and once a month in 1. All patients had status epilepticus in the early course of epilepsy. EEGs showed parieto-occipital spikes in all patients. MRI revealed cortical atrophy and T2 prolongation parieto-occipitally in 4 patients, hippocampal atrophy in 1, and unremarkable in 1. This study indicates that epilepsy secondary to neonatal hypoglycemia is intractable during infancy and early childhood with frequent status epilepticus but tends to decrease in older age.

Reexamining the Hypoglycemia Fear Survey for Parents of Young Children in a Sample of Children Using Insulin Pumps.

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Patton, Susana R; Noser, Amy E; Clements, Mark A; Dolan, Lawrence M; Powers, Scott W

2017-02-01

We update the psychometric properties of the Hypoglycemia Fear Survey-Parents of Young Children (HFS-PYC), a 26-item measure of parents' hypoglycemia fear for young children using an insulin pump. We combined three similar datasets for the analyses. The data analyzed included parents' responses to the HFS-PYC and a demographic form. For a subset of children (n = 91), we also analyzed self-monitoring of blood glucose data. We used confirmatory factor analysis (CFA) to confirm the measure's original factor structure. Additional analyses examined reliability and validity of a revised HFS-PYC for parents of young children using pumps. We analyzed data from 116 parents (93% mothers). Mean child age and HbA1c were 5.2 ± 1.3 years and 8.2% ± 1.1%, respectively. CFA identified a 22-item two-factor solution (χ 2 (208, n = 116) = 368.688, P 0.65). Correlations revealed significant negative associations between current HFS-PYC worry scores and children's mean daily blood glucose and percent of very high glucose levels per day, suggesting less fear among parents of young children with elevated glycemic levels. In addition, there was a positive association with the percent of glucose levels in target, suggesting greater hypoglycemia fear among parents of children who have better control. Results provide preliminary evidence for the reliability and validity of a reduced 22-item HFS-PYC for parents of children using insulin pumps.

Nocturnal Hypoglycemia in Type 2 Diabetes

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Clus Simona

2018-03-01

Full Text Available Background and aims: It is known that the majority of critical unacknowledged hypoglycemia has an increased incidence in patients with type 1 diabetes (T1DM with a long evolution. The aim of this research is to evaluate the variability of glucose level and hypoglycemic events in patients with type 2 diabetes (T2DM having pharmacological interventions with hypoglycemic risk. These events are sometimes asymptomatic also in T2DM: frequently in elderly, patients with autonomic neuropathy, or having a long evolution of disease.

Theophylline enhances glucose recovery after hypoglycemia in healthy man and in type I diabetic patients

DEFF Research Database (Denmark)

Hvidberg, A; Rasmussen, M H; Christensen, N J

1994-01-01

followed by IV infusion of 1 mg/kg/h) was administered from 1 hour before induction of hypoglycemia until the end of the study period. On the other day, NaCl was administered. Plasma glucose before induction of hypoglycemia was equal on the 2 study days. The plasma glucose area under the curve (AUC......). The incremental AUC for cAMP was larger with theophylline for diabetic patients (P = .01). For healthy subjects, cAMP was greater with theophylline 30 minutes after insulin (P = .03). In conclusion, glucose recovery after hypoglycemia is significantly increased when theophylline is administered in an asthma......The principal mediators of glucose counterregulation (glucagon and epinephrine) use intracellular cyclic adenosine monophosphate (cAMP) to mediate glucose release. Since theophylline increases cAMP (by inhibiting its decomposition), we investigated the effect of theophylline on glucose recovery...

INCIDENCE & CAUSES OF NEONATAL HYPOGLYCEMIA AFTER CESAREAN SECTION IN A RURAL SETUP OF WEST BENGAL

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Rudradev; Anirban; Abhijit; Maitreyi; Banani; Srimanta; Loknath; Bhaskar

2014-01-01

Neonatal hypoglycaemia a major cause of morbidity and mortality may lead to permanent brain damage. This is more common in babies delivered by Caesar ean Section. AIMS: A clinico - statistical study was performed among newborns delivered by Caesarean Section for a period of 1 year to find out: 1. The incidence of neonatal hypoglycemia at 48 hrs of birth. 2. Risk factors of neonatal hypoglycemia in case of cesarean section. 3. Incidence of neonat...

Hypoglycemia-related electroencephalogram changes are independent of gender, age, duration of diabetes, and awareness status in type 1 diabetes

DEFF Research Database (Denmark)

Remvig, Line Sofie; Elsborg, Rasmus; Sejling, Anne-Sophie

2012-01-01

Introduction: Neuroglycopenia in type 1 diabetes mellitus (T1DM) results in reduced cognition, unconsciousness, seizures, and possible death. Characteristic changes in the electroencephalogram (EEG) can be detected even in the initial stages. This may constitute a basis for a hypoglycemia alarm...... device. The aim of the present study was to explore the characteristics of the EEG differentiating normoglycemia and hypoglycemia and to elucidate potential group differences. Methods: We pooled data from experiments in T1DM where EEG was available during both normoglycemia and hypo-glycemia for each...

Spanish translation, adaptation and validation of the Hypoglycemia Fear Survey in adults with type 1 diabetes in the Community of Madrid.

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Tasende, Clara; Rubio, José Antonio; Álvarez, Julia

2018-05-01

The negative impact of hypoglycemia on patients with type 1 diabetes mellitus (T1DM) may lead to development of fear of hypoglycemia. In this study, the original Hypoglycemia Fear Survey (HFS) questionnaire was translated into Spanish, adapted and validated, and variables associated to fear of hypoglycemia in T1DM were analyzed. The HFS was translated and adapted to Spanish using the forward-backward translation method. The resulting questionnaire, EsHFS, was administrated to a population with T1DM. The following parameters of the questionnaire were analyzed: feasibility, reliability (Cronbach's alpha), content validity (correlating EsHFS and EsDQOL [Diabetes Quality of Life] questionnaire), and stability (by means of test-retest correlation). The EsHFS questionnaire consists of 24 items and three subscales including: subscale 1 on worry; subscale 2 on hypoglycemia-avoidant behavior, and subscale 3 on hyperglycemia-influenced behavior. 163 subjects, with a mean aged (SD) of 36 (10.5) years, 24% on continuous subcutaneous insulin infusion. Of these, 99.8% completed the EsHFS questionnaire in less than 10minutes. Cronbach's alpha for global EsHFS was 0.92. EsHFS and its subscales correlated with EsDQOL. Test-retest correlation (Pearson) was r=0.92. Age, female sex, lower educational level, living alone, frequency of daily self-monitoring and non-severe hypoglycemia, and history of severe and/or asymptomatic hypoglycemia were independently associated to the result of EsHFS. The Spanish version of the HFS, EsHFS, has good psychometric properties and may be a useful tool to assess fear of hypoglycemia in Spanish-speaking patients with T1DM. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Symptomatic Hypoglycemia Related to Inappropriately High IGF-II Serum Levels in a Patient with Desmoplastic Small Round Cell Tumor

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Williams Fernandes Barra

2010-01-01

Full Text Available A 45-year old man was diagnosed with desmoplastic small round cell tumor (DSRCT with involvement of the peritoneum and pelvis. Disease progression was observed despite systemic chemotherapy. Six months after diagnosis, he developed severe hypoglycemia presented with seizures. He received intravenous glucose infusion and hydrocortisone with poor glycemic control, but with seizures resolution. The investigation excluded insulinoma, adrenal, liver and GH deficiencies. Laboratory showed slight rise of IGF-II and significant increase of the ratio IGF-II : IGF-I, which is pathognomonic of non-islet cell tumor hypoglycemia (NICTH. He received the diagnoses of NICTH related to IGF-II inappropriate production by DSRCT. Despite the attempt to control tumor mass and hypoglycemia, the patient died 9 months after diagnosis. NICTH related to inappropriate IGF-II secretion should be investigated in all cancer patients with refractory hypoglycemia whom insulinoma and other metabolic abnormalities were excluded from.

Blocking of beta-2 adrenergic receptors hastens recovery from hypoglycemia-associated social withdrawal.

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Park, Min Jung; Guest, Christopher B; Barnes, Meredith B; Martin, Jonathan; Ahmad, Uzma; York, Jason M; Freund, Gregory G

2008-11-01

Hypoglycemia is associated with a variety of adverse behaviors including fatigue, confusion and social withdrawal. While these clinical symptoms are well characterized, the mechanism of their cause is not understood. Here we investigated how insulin-induced hypoglycemia causes social withdrawal. Male 8-12-week-old C57BL/6J mice were injected intraperitoneally (IP) with or without and/or insulin, norepinephrine (NE) and epinephrine (Epi), terbutaline and butoxamine with subsequent measurement of blood glucose, social withdrawal and plasma catecholamines. Insulin generated (0.75h post-injection) significant hypoglycemia with blood glucose nadirs of 64+/-4 and 48+/-5mg/dl for 0.8 and 1.2units/kg of insulin, respectively. Insulin (0.8 or 1.2units/kg) caused near total social withdrawal at 0.75h with full recovery not occurring until 4h (0.8units/kg) or 8h (1.2units/kg) post-insulin injection. Insulin also caused a marked elevation in plasma catecholamines. Basal 12h fasting NE and Epi were 287+/-38 and 350+/-47pg/ml, respectively. Insulin at 0.8units/kg increased plasma NE and Epi to 994+/-73 and 1842+/-473pg/ml, respectively. Administration of exogenous NE or Epi caused social withdrawal similar in magnitude to insulin. Importantly, administration of the beta-2 adrenergic receptor agonist terbutaline also caused social withdrawal while administration of the beta-2 adrenergic receptor antagonist butoxamine blocked NE-induced social withdrawal. Finally, butoxamine blocked insulin-induced social withdrawal. These data demonstrate that hypoglycemia-associated social withdrawal is dependent on catecholamines via a beta-2 receptor-mediated pathway.

Generalized Anxiety Disorder and Hypoglycemia Symptoms Improved with Diet Modification.

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Aucoin, Monique; Bhardwaj, Sukriti

2016-01-01

Observational evidence suggests that a relationship may exist between high glycemic index diets and the development of anxiety and depression symptoms; however, as no interventional studies assessing this relationship in a psychiatric population have been completed, the possibility of a causal link is unclear. AB is a 15-year-old female who presented with concerns of generalized anxiety disorder and hypoglycemia symptoms. Her diet consisted primarily of refined carbohydrates. The addition of protein, fat, and fiber to her diet resulted in a substantial decrease in anxiety symptoms as well as a decrease in the frequency and severity of hypoglycemia symptoms. A brief return to her previous diet caused a return of her anxiety symptoms, followed by improvement when she restarted the prescribed diet. This case strengthens the hypothesis that dietary glycemic index may play a role in the pathogenesis or progression of mental illnesses such as generalized anxiety disorder and subsequently that dietary modification as a therapeutic intervention in the treatment of mental illness warrants further study.

Fatty acid turnover, substrate oxidation, and heat production in lean and obese cats during the euglycemic hyperinsulinemic clamp.

Science.gov (United States)

Hoenig, M; Thomaseth, K; Waldron, M; Ferguson, D C

2007-05-01

Simultaneous application of the euglycemic hyperinsulinemic clamp (EHC) and indirect calorimetry was used to examine heat production, fat, and glucose metabolism in lean and obese adult neutered male and female cats. The results show that in lean insulin-sensitive cats glucose oxidation predominated during fasting, whereas lipid oxidation became more prominent in obese cats. Insulin infusion during the EHC in lean cats and obese male cats led to a large increase in glucose oxidation, glycogenesis, and lipogenesis. It also led to an increase in glucose oxidation and glycogenesis in obese female cats but it was significantly less compared to lean cats and obese males. This indicates that obese females show greater metabolic inflexibility. In obese cats of either gender, insulin caused greater suppression of non-esterified fatty acids compared to lean cats suggesting that obese cats show greater fatty acid clearance than lean cats. The heat production per metabolic size was lower in obese cats than lean cats. This would perpetuate obesity unless food intake is decreased. The higher glucose oxidation rate in obese neutered male cats suggests that they are able to replete their glycogen and lipid stores at a faster rate than females in response to insulin and it implies that they gain weight more rapidly. Further studies are needed to investigate if the different response to insulin of male cats is involved in their higher risk to develop diabetes.

Dextrose boluses versus burette dextrose infusions in prevention of hypoglycemia among preterms admitted at Mulago Hospital: an open label randomized clinical trial.

Science.gov (United States)

Kutamba, E; Lubega, S; Mugalu, J; Ouma, J; Mupere, E

2014-09-01

Hypoglycemia is a major cause of morbidity and mortality among preterm infants and its management remains a challenge in resource limited settings. Use of dextrose infusion by the recommended infusion pumps is not feasible in our environment due to their high costs and yet the current use of mini dextrose boluses with syringes as adapted at Mulago national referral and tertiary teaching hospital has unknown efficacy in prevention of hypoglycemia. We determined the efficacy of dextrose infusions by burettes versus two hourly dextrose boluses in prevention of hypoglycemia among preterms admitted in the first 72 hours at Special Care Unit, Mulago Hospital. One hundred and forty preterms aged 0 to 24 hours of life were randomized to receive 10% IV dextrose either as mini boluses or by infusion using burettes in an open label clinical trial. Blood glucose was measured at 0, two hourly for next 6 hours, 6 hourly for next 12 hours and thereafter 12 hourly until end of 72 hours following admission. Primary end point was incidence of hypoglycemia (random blood sugar (RBS) dextrose infusion was computed using 1-RR. From February 2012 to April 2012, 68 preterms in the bolus arm and 72 in the infusion arm were studied. Hypoglycemia was detected in 34% (48/140). The incidence of hypoglycemia in the bolus arm was 59% (40/68) compared to 11% (8/72) in the infusion arm (RR; 0.19, 95% CI; 0.09-0.37). Efficacy (1-RR) of infusion by burettes versus boluses in prevention of hypoglycemia among preterms was 0.81 (95% CI; 0.63-0.90). Continuous 10% dextrose infusion by burettes reduced the incidence of hypoglycemia by 81% in the first 72 hours of admission compared to two hourly 10% mini dextrose boluses among preterms admitted at Special Care Unit, Mulago Hospital. (ClinicalTrials.gov Identifier: NCT01688674).

Severe paraneoplastic hypoglycemia in a patient with a gastrointestinal stromal tumor with an exon 9 mutation: a case report

International Nuclear Information System (INIS)

Escobar, Guillermo A; Robinson, William A; Nydam, Trevor L; Heiple, Drew C; Weiss, Glen J; Buckley, Linda; Gonzalez, Rene; McCarter, Martin D

2007-01-01

Non-islet cell tumor induced hypoglycemia (NICTH) is a very rare phenomenon, but even more so in gastrointestinal stromal tumors. It tends to present in large or metastatic tumors, and can appear at any time in the progression of the disease. We present herein a case of NICTH in a GIST tumor and report an exon 9 mutation associated to it. A thirty nine year-old man with a recurrent, metastatic gastrointestinal stromal tumor presented to the hospital with nausea, dizziness, loss of consciousness, and profound hypoglycemia (20 mg/dL). There was no evidence of factitious hypoglycemia. He was stabilized with a continuous glucose infusion and following selective vascular embolization, the patient underwent debulking of a multicentric 40 cm × 25 cm × 10 cm gastrointestinal stromal tumor. After resection, the patient became euglycemic and returned to his normal activities. Tumor analysis confirmed excessive production of insulin-like growth factor II m-RNA and the precursor protein, 'big' insulin-like growth factor II. Mutational analysis also identified a rare, 6 bp tandem repeat insert (gcctat) at position 1530 in exon 9 of KIT. Optimal management of gastrointestinal stromal tumor-induced hypoglycemia requires a multidisciplinary approach, and surgical debulking is the treatment of choice to obtain immediate symptom relief. Imatinib or combinations of glucocorticoids and growth hormone are alternative palliative strategies for symptomatic hypoglycemia. In addition, mutations in exon 9 of the tyrosine kinase receptor KIT occur in 11–20% of GIST and are often associated with poor patient outcomes. The association of this KIT mutation with non-islet cell tumor induced hypoglycemia has yet to be established

The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp.

Science.gov (United States)

Guerrero-Romero, Fernando; Simental-Mendía, Luis E; González-Ortiz, Manuel; Martínez-Abundis, Esperanza; Ramos-Zavala, María G; Hernández-González, Sandra O; Jacques-Camarena, Omar; Rodríguez-Morán, Martha

2010-07-01

To meet the worldwide challenge of emerging diabetes, accessible and inexpensive tests to identify insulin resistance are needed. To evaluate the sensitivity and specificity of the product of fasting, we compared the triglycerides and glucose (TyG) index, a simple measure of insulin resistance, with the euglycemic-hyperinsulinemic clamp test. We conducted a cross-sectional study of the general population and outpatients of the Internal Medicine Department at the Medical Unit of High Specialty of the Specialty Hospital at the West National Medical Center in Guadalajara, Mexico. Eleven nonobese healthy subjects, 34 obese normal glucose tolerance individuals, 22 subjects with prediabetes, and 32 diabetic patients participated in the study. We performed a euglycemic-hyperinsulinemic clamp test. Sensitivity and specificity of the TyG index [Ln(fasting triglycerides) (mg/dl) x fasting glucose (mg/dl)/2] were measured, as well as the area under the curve of the receiver operating characteristic scatter plot and the correlation between the TyG index and the total glucose metabolism (M) rates. Pearson's correlation coefficient between the TyG index and M rates was -0.681 (P index and M rates was similar between men (-0.740) and women (-0.730), nonobese (-0.705) and obese (-0.710), and nondiabetic (-0.670) and diabetic (-0.690) individuals. The best value of the TyG index for diagnosis of insulin resistance was 4.68, which showed the highest sensitivity (96.5%) and specificity (85.0%; area under the curve + 0.858). The TyG index has high sensitivity and specificity, suggesting that it could be useful for identification of subjects with decreased insulin sensitivity.

Dipyrone in association with atropine inhibits the effect on gastric emptying induced by hypoglycemia in rats

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E.F. Collares

2017-08-01

Full Text Available Atropine (AT and dipyrone (Dp induce a delay of gastric emptying (GE of liquids in rats by inhibiting muscarinic receptors and activating β2-adrenergic receptors, respectively. The objective of the present study was to determine the effects of pretreatment with AT and Dp, given alone or in combination, on the effect of hypoglycemia in the liquid GE in rats. Male Wistar adult rats (280-310 g were pretreated intravenously with AT, Dp, AT plus Dp or their vehicle and then treated 30 min later with iv insulin or its vehicle (n=8-10 animals/group. Thirty min after treatment, GE was evaluated by determining, in awake rats, the percent gastric retention (%GR of a saline meal labeled with phenol red administered by gavage. The results indicated that insulin induced hypoglycemia in a dose-dependent manner resulting in a significant reduction in %GR of liquid only at the highest dose tested (1 U/kg. Pretreatment with AT significantly increased %GR in the rats treated with 1 U/kg insulin. Surprisingly, after pretreatment with AT, the group treated with the lowest dose of insulin (0.25 U/kg displayed significantly lower %GR compared to its control (vehicle-treated group, which was not seen in the non-pretreated animals. Pretreatment with Dp alone at the dose of 40 mg/kg induced an increase in %GR in both vehicle and 0.25 U/kg-treated rats. A higher dose of Dp alone (80 mg/kg significantly reduced the effect of a marked hypoglycemia induced by 1 U/kg of insulin on GE while in combination with AT the effect was completely abolished. The results with AT suggest that moderate hypoglycemia may render the inhibitory mechanisms of GE ineffective while Dp alone and in combination with AT significantly overcame the effect of hypoglycemia on GE.

Hypoglycemia-Associated EEG Changes in Prepubertal Children With Type 1 Diabetes

DEFF Research Database (Denmark)

Hansen, Grith Lærkholm; Foli-Andersen, Pia; Fredheim, Siri

2016-01-01

were calculated. A within-patient analysis was conducted comparing hypoglycemia versus euglycemia changes in the qEEG. The nonparametric Wilcoxon signed rank test was performed. A real-time analyzing algorithm developed for adults was applied. RESULTS: The qEEG showed significant differences...

Profound hypoglycemia-ınduced by vaccinium corymbosum juice and laurocerasus fruit.

Science.gov (United States)

Aktan, Ahmet Hamdi; Ozcelik, Abdullah; Cure, Erkan; Cure, Medine Cumhur; Yuce, Suleyman

2014-01-01

An emergency intervention was performed in a 75-year-old male patient with hypoglycemic attack and blackout. Although he was diagnosed with prediabetes before 2 years, he did not take any anti-diabetic drug or follow dietary advice. He drank Vaccinium corymbosum L (VC) juice daily with a belief that it increases sexual potency. Before the development of hypoglycemia, the patient had consumed about 500 ml VC juice in addition to eating 200-300 gram of Laurocerasus officinalis (LO) fruit. The measured plasma glucose (PG) level during loss of consciousness was 30 mg/dl. The profound hypoglycemia may be an unexpected side effect of an interaction between the chemical compositions of the two plants, occurred as a result of LO fruit intake that may have a strong PG-lowering effect or related to excessive intake of VC juice. Both plants may be considered in the alternative treatment of diabetes.

Impact of screening and monitoring of capillary blood glucose in the detection of hyperglycemia and hypoglycemia in non-critical inpatients

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Rogerio Silicani Ribeiro

2011-03-01

Full Text Available Objective: To evaluate the impact of screening hyper and hypoglycemia measured by capillary glycemia and standard monitorization of  hyperglycemic patients hospitalized in regular care units of Hospital Israelita Albert Einstein. Methods: The capillary glycemia was  measured by the Precision PCx (Abbott glucosimeter, using the PrecisionWeb (Abbott software. The detection of hyper and hypoglycemia during the months of May/June were compared to those of March/April in 2009 and to the frequency of the diagnosis of diabetes in 2007. Rresults: There was an increase in the glycemia screening from 27.7 to 77.5% of hospitalized patients (p < 0.001, of hyperglycemia detection (from 9.3 to 12.2%; p < 0.001 and of hypoglycemia (from 1.5 to 3.3%; p < 0.001 during  the months of May/June  2009. According to this action 14 patients for each additional case of hyperglycemia and 26 cases for each case of hypoglycemia were identified. The detection of hyperglycemia was significantly higher (p < 0.001 than the frequency of registered diagnosis related do diabetes in the year of 2007. Cconclusions: the adoption of an institutional program of glycemia monitorization improves the detection of hyper and hypoglycemia and glycemia control in hospitalized patients in regular care units.

Development and validation of a prediction model for insulin-associated hypoglycemia in non-critically ill hospitalized adults.

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Mathioudakis, Nestoras Nicolas; Everett, Estelle; Routh, Shuvodra; Pronovost, Peter J; Yeh, Hsin-Chieh; Golden, Sherita Hill; Saria, Suchi

2018-01-01

To develop and validate a multivariable prediction model for insulin-associated hypoglycemia in non-critically ill hospitalized adults. We collected pharmacologic, demographic, laboratory, and diagnostic data from 128 657 inpatient days in which at least 1 unit of subcutaneous insulin was administered in the absence of intravenous insulin, total parenteral nutrition, or insulin pump use (index days). These data were used to develop multivariable prediction models for biochemical and clinically significant hypoglycemia (blood glucose (BG) of ≤70 mg/dL and model development and validation, respectively. Using predictors of age, weight, admitting service, insulin doses, mean BG, nadir BG, BG coefficient of variation (CV BG ), diet status, type 1 diabetes, type 2 diabetes, acute kidney injury, chronic kidney disease (CKD), liver disease, and digestive disease, our model achieved a c-statistic of 0.77 (95% CI 0.75 to 0.78), positive likelihood ratio (+LR) of 3.5 (95% CI 3.4 to 3.6) and negative likelihood ratio (-LR) of 0.32 (95% CI 0.30 to 0.35) for prediction of biochemical hypoglycemia. Using predictors of sex, weight, insulin doses, mean BG, nadir BG, CV BG , diet status, type 1 diabetes, type 2 diabetes, CKD stage, and steroid use, our model achieved a c-statistic of 0.80 (95% CI 0.78 to 0.82), +LR of 3.8 (95% CI 3.7 to 4.0) and -LR of 0.2 (95% CI 0.2 to 0.3) for prediction of clinically significant hypoglycemia. Hospitalized patients at risk of insulin-associated hypoglycemia can be identified using validated prediction models, which may support the development of real-time preventive interventions.

Prevalence and possible mechanisms of reactive hypoglycemia in polycystic ovary syndrome

DEFF Research Database (Denmark)

Mumm, Hanne; Altinok, Magda Lambaa; Henriksen, Jan Erik

2016-01-01

STUDY QUESTION: What is the prevalence of reactive hypoglycemia (RH) in polycystic ovary syndrome (PCOS) versus age- and body mass index (BMI)-matched healthy controls. SUMMARY ANSWER: The prevalence of RH was increased in PCOS versus controls. WHAT IS KNOWN ALREADY: Previous studies suggested...

Malignant phyllodes tumor of the breast presenting with hypoglycemia: a case report and literature review

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Pacioles T

2014-12-01

Full Text Available Toni Pacioles,1 Rahul Seth,2,3 Cesar Orellana,3 Ivy John,4 Veera Panuganty,3 Ruban Dhaliwal3,5 1Department of Hematology and Oncology, Edwards Comprehensive Cancer Center, Marshall University, Huntington, WV, USA; 2Division of Hematology and Oncology, 3Department of Medicine, 4Department of Pathology, 5Division of Endocrinology, SUNY Upstate Medical University, Syracuse, NY, USA Abstract: Phyllodes tumors are rare fibroepithelial neoplasms that account for less than 1% of all breast tumors and are typically found in middle-aged women. Phyllodes tumors that present with hypoglycemia are even rarer. No one morphologic finding is reliable in predicting the clinical behavior of this tumor. Surgery has been the primary mode of treatment to date. However, the extent of resection and the role of adjuvant radiotherapy or chemotherapy are still controversial. Here, we present a challenging case of malignant phyllodes tumor of the breast associated with hypoglycemia, and review the literature regarding clinical findings, pathologic risk factors for recurrence, and treatment recommendations. Keywords: breast cancer, fibroepithelial neoplasm, neuroendocrine tumor, adjuvant treatment, non-islet cell tumor-induced hypoglycemia

Generalized Anxiety Disorder and Hypoglycemia Symptoms Improved with Diet Modification

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Monique Aucoin

2016-01-01

Full Text Available Observational evidence suggests that a relationship may exist between high glycemic index diets and the development of anxiety and depression symptoms; however, as no interventional studies assessing this relationship in a psychiatric population have been completed, the possibility of a causal link is unclear. AB is a 15-year-old female who presented with concerns of generalized anxiety disorder and hypoglycemia symptoms. Her diet consisted primarily of refined carbohydrates. The addition of protein, fat, and fiber to her diet resulted in a substantial decrease in anxiety symptoms as well as a decrease in the frequency and severity of hypoglycemia symptoms. A brief return to her previous diet caused a return of her anxiety symptoms, followed by improvement when she restarted the prescribed diet. This case strengthens the hypothesis that dietary glycemic index may play a role in the pathogenesis or progression of mental illnesses such as generalized anxiety disorder and subsequently that dietary modification as a therapeutic intervention in the treatment of mental illness warrants further study.

Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats

International Nuclear Information System (INIS)

Schwartz, M.W.; Figlewicz, D.F.; Kahn, S.E.; Baskin, D.G.; Greenwood, M.R.; Porte, D. Jr.

1990-01-01

In order to study the role of plasma insulin in regulating the binding of insulin to the endothelium of the blood-brain barrier (BBB), insulin binding to a purified preparation of brain capillaries was measured in both genetically obese Zucker rats and lean Zucker controls. We found a reduction of 65% in brain capillary insulin binding site number in the obese compared to lean rats with no change in receptor affinity. Furthermore, specific insulin binding to brain capillaries was negatively correlated (p less than 0.05) to the plasma insulin level, suggesting a role for plasma insulin in regulating insulin binding. A similar relationship was observed between insulin receptor number in liver membranes and the plasma insulin level. We conclude that obese, hyperinsulinemic Zucker rats exhibit a reduction in the number of BBB insulin receptors, which parallels the reduction seen in other peripheral tissues. Since insulin receptors have been hypothesized to participate in the transport of insulin across the BBB, the reduction observed in the obese rats may account for the decrease in cerebrospinal fluid insulin uptake previously demonstrated in these animals

Neonatal hypoglycemia: A wide range of electroclinical manifestations and seizure outcomes.

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Arhan, Ebru; Öztürk, Zeynep; Serdaroğlu, Ayşe; Aydın, Kürşad; Hirfanoğlu, Tuğba; Akbaş, Yılmaz

2017-09-01

We examined the various types of epilepsy in children with neonatal hypoglycemia in order to define electroclinical and prognostic features of these patients. We retrospectively reviewed the medical records of patients with a history of symptomatic neonatal hypoglycaemia who have been followed at Gazi University Hospital Pediatric Neurology Department between 2006 and 2015. Patients with perinatal asphyxia were excluded. Details of each patient's perinatal history, neurological outcome, epilepsy details, seizure outcome and EEG and brain MRI findings were reviewed. Fourty five patients (range 6 mo-15 y) with a history of symptomatic neonatal hypoglycaemia were included the study. Epilepsy developed in 36 patients and 23 of them had intractable epilepsy. All patients had occipital brain injury. We observed that most of the patients, either manifesting focal or generalized seizures, further develop intractable epilepsy. This finding establishes neonatal hypoglycemia as a possible cause to be considered in any case of intractable epilepsy. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Enhanced 911/global position system wizard: a telemedicine application for the prevention of severe hypoglycemia--monitor, alert, and locate.

Science.gov (United States)

Dassau, Eyal; Jovanovic, Lois; Doyle, Francis J; Zisser, Howard C

2009-11-01

Intensive insulin therapy has an inherent risk of hypoglycemia that can lead to loss of consciousness, cardiac arrhythmia, seizure, and death ("dead-in-bed syndrome"). This risk of hypoglycemia is a major concern for patients, families, and physicians. The need for an automated system that can alert in the event of severe hypoglycemia is evident. In engineering systems, where there is a risk of malfunction of the primary control system, alert and safety mechanisms are implemented in layers of protection. This concept has been adopted in the proposed system that integrates a hypoglycemia prediction algorithm with a global position system (GPS) locator and short message service such that the current glucose value with the rate of change (ROC) and the location of the subject can be communicated to a predefined list. Furthermore, if the system is linked to the insulin pump, it can suspend the pump or decrease the basal insulin infusion rate to prevent the pending event. The system was evaluated on clinical datasets of glucose tracings from the DexCom Seven system. Glucose tracings were analyzed for hypoglycemia events and then a text message was broadcast to a predefined list of people who were notified with the glucose value, ROC, GPS coordinates, and a Google map of the location. In addition to providing a safety layer to a future artificial pancreas, this system also can be easily implemented in current continuous glucose monitors to help provide information and alerts to people with diabetes.

The lactate receptor HCAR1 promotes neuronal development and protects axons and myelin during hypoglycemia

DEFF Research Database (Denmark)

Kennedy, L. H.; Andersson, K. A.; Haugen, O. P.

2017-01-01

Lactate plays a significant role as an energy supply for neurons and has a neuroprotective effect in hypoglycemia and ischemia (1±5). Further, oligodendrocytes can use lactate for myelination when glucose levels are low. New studies suggest that lactate is not only a metabolic fuel but also...... in the development and survival of neurons and oligodendrocytes in normal conditions and hypoglycemia. We show that young HCAR1 KO mice have a reduced number of neural progenitor cells in the hippocampus and the cerebral cortex, and the average size of cortical axons is smaller in KO compared with WT mice...

Doege-Potter syndrome presenting with hypoinsulinemic hypoglycemia in a patient with a malignant extrapleural solitary fibrous tumor: a case report

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Schutt Robert C

2013-01-01

Full Text Available Abstract Introduction Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. This tumor causes hypoglycemia by the secretion of a prohormone form of insulin-like growth factor II. We describe the diagnosis and management of Doege-Potter syndrome and the use of transarterial chemoembolization in a patient with a malignant extrapleural solitary fibrous tumor. Case presentation Our patient was a 64-year-old Caucasian woman who initially presented with urinary incontinence and was found to have a 14.5×9.0×9.0cm retroperitoneal solitary fibrous tumor compressing her bladder. Her tumor was surgically resected but recurred with multiple hepatic metastatic lesions. The hepatic metastases progressed despite systemic chemotherapy and treatment with doxorubicin transarterial chemoembolization. Her course was complicated by the development of recurrent fasting hypoglycemia, most likely secondary to Doege-Potter syndrome. Her hypoglycemia was managed with corticosteroid therapy and frequent scheduled nutrient intake overnight. Conclusions The rarity of hepatic solitary fibrous tumors and consequent lack of controlled trials make this report significant in that it describes the diagnostic approach to Doege-Potter syndrome, describes our experience with the use of doxorubicin transarterial chemoembolization, and presents management options for tumor-associated hypoglycemia in the case of extensive disease not amenable to surgical resection.

Impact of hypoglycemia on daily life of type 2 diabetes patients in Ukraine

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Mandrik O

2013-07-01

Full Text Available Olena Mandrik,1–3 Johan L Severens,1 Olena Doroshenko,4 Vladymir Pan'kiv,5 Nonna Kravchun,6 Maryna Vlasenko,7 Mykola Hulchiy,8 Maryna Baljuk,9 Yuliia Komisarenko,10 Eugene Martsynik,11 Liubov Sokolova,12 Olga Zalis'ka,2 Boris Mankovsky131Erasmus University Rotterdam, Rotterdam, the Netherlands; 2Danylo Halytsky Lviv National Medical University, Lviv, 3MSD Ukraine, 4Ukrainian Institute for Strategic Research, 5Ukrainian Scientific Centre of Endocrine Surgery, 6Institute of Problems of Endocrine Pathology na VY Danylevskogo, Ukrainian Academy of Medical Sciences, Kyiv, 7Vinnitsa National Medical University named after MI Pyrogov, Vinnytsia, 8Kyiv City Teaching Endocrinological Center, Kyiv, 9Danilevsky Institute of Endocrine Pathology Problems, Ukrainian Academy of Medical Sciences, Kharkov, 10OO Bogomolets National Medical University, Kyiv, 11Medical Academy of Dnepropetrovsk, Dnepropetrovsk, 12Institute of Endocrinology and Metabolism after V.P. Komissarenko, National Academy of Medical Sciences of Ukraine, Kyiv, 13PL Shupik National Medical Academy of Postgraduate Education, Kyiv, UkraineAbstract: This study evaluates the impact of hypoglycemia on the lives of Ukrainian patients with type 2 diabetes mellitus. The secondary objective was to explore patient–physician relationships and the attitudes of patients towards various informational resources on diabetes management. Three focus groups with 26 patients were conducted. Qualitative information was evaluated using content analysis. The results show that patients with type 2 diabetes mellitus in Ukraine are adapting to potential attacks of hypoglycemia; however, they still experience periodic manifestations of hypoglycemia that significantly affect their psychological well-being. This result is similar to observations made in other countries. Ukrainian patients >40 years old mainly receive information on disease management from endocrinologists, and rarely use internet resources on diabetes

A Comparative Study of Blood Glucose Measurements Using Glucometer Readings and the Standard Method in the Diagnosis of Neonatal Hypoglycemia

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Mohammad Torkaman

2016-03-01

Full Text Available Background: Hypoglycemia is one of the most common neonatal disorders, associated with severe complications. There has been a great deal of controversy regarding the definition and screening of hypoglycemia. Therefore, in this study, we aimed to determine a cut-off value for blood glucose level in glucometer readings. Methods: This cross-sectional study was conducted on 238 newborns at risk of hypoglycemia, admitted to Baqiyatallah Hospital of Tehran, Iran in 2012; the subjects were selected via simple sampling. After obtaining informed consents from the newborns’ parents, 1 cc blood samples were sent to the laboratory for measuring the blood glucose level. Moreover, venous blood samples, as well as heel-stick blood samples, were obtained for glucometer measurements. Blood glucose measurements were used to determine the cut-off value by the receiver operating characteristic (ROC curve and make comparisons with the diagnostic criteria for hypoglycemia in the literature. Results: A total of 238 infants with the mean weight of 2869±821.9 g were enrolled in this study. The mean (±SD blood glucose levels were 65.1±22.9, 82.9±24.7, and 84.4±24.8 mg/dl, based on the standard laboratory method, glucometer reading of venous blood samples, and glucometer reading of heel-stick capillary blood samples, respectively. The optimal cut-off point for hypoglycemia was determined as 65 mg/dl, using glucometer-based assessment of heel-stick blood samples. Conclusion: The significant difference in blood glucose levels measured by the laboratory method and outpatient glucometer readings highlights the importance of a cut-off value for rapid assessment and control of blood glucose and timely detection of hypoglycemia. In fact, the cut-off value introduced in the present study could facilitate such measurements.

Inborn Errors of Metabolism with Hypoglycemia Glycogen Storage Diseases and Inherited Disorders of Gluconeogenesis : Glycogen Storage Diseases and Inherited Disorders of Gluconeogenesis

NARCIS (Netherlands)

Weinstein, David A.; Steuerwald, Ulrike; De Souza, Carolina F. M.; Derks, Terry G. J.

Although hyperinsulinism is the predominant inherited cause of hypoglycemia in the newborn period, inborn errors of metabolism are the primary etiologies after 1 month of age. Disorders of carbohydrate metabolism often present with hypoglycemia when fasting occurs. The presentation, diagnosis, and

Dextrose 10% in the treatment of out-of-hospital hypoglycemia.

Science.gov (United States)

Kiefer, Matthew V; Gene Hern, H; Alter, Harrison J; Barger, Joseph B

2014-04-01

Prehospital first responders historically have treated hypoglycemia in the field with an IV bolus of 50 mL of 50% dextrose solution (D50). The California Contra Costa County Emergency Medical Services (EMS) system recently adopted a protocol of IV 10% dextrose solution (D10), due to frequent shortages and relatively high cost of D50. The feasibility, safety, and efficacy of this approach are reported using the experience of this EMS system. Over the course of 18 weeks, paramedics treated 239 hypoglycemic patients with D10 and recorded patient demographics and clinical outcomes. Of these, 203 patients were treated with 100 mL of D10 initially upon EMS arrival, and full data on response to treatment was available on 164 of the 203 patients. The 164 patients' capillary glucose response to initial infusion of 100 mL of D10 was calculated and a linear regression line fit between elapsed time and difference between initial and repeat glucose values. Feasibility, safety, and the need for repeat glucose infusions were examined. The study cohort included 102 men and 62 women with a median age of 68 years. The median initial field blood glucose was 38 mg/dL, with a subsequent blood glucose median of 98 mg/dL. The median time to second glucose testing was eight minutes after beginning the 100 mL D10 infusion. Of 164 patients, 29 (18%) required an additional dose of IV D10 solution due to persistent or recurrent hypoglycemia, and one patient required a third dose. There were no reported adverse events or deaths related to D10 administration. Linear regression analysis of elapsed time and difference between initial and repeat glucose values showed near-zero correlation. In addition to practical reasons of cost and availability, theoretical risks of using 50 mL of D50 in the out-of-hospital setting include extravasation injury, direct toxic effects of hypertonic dextrose, and potential neurotoxic effects of hyperglycemia. The results of one local EMS system over an 18-week

Hypoglycemia and severe lactic acidosis in a dog following metformin exposure

OpenAIRE

Barrella, Nicole; Eisenberg, Beth; Simpson, Stephanie Nicole

2017-01-01

Key Clinical Message Hypoglycemia and lactic acidosis are rare complications with metformin use in humans. As metformin is not commonly used in veterinary medicine, severe adverse effects secondary to exposure are not known. Awareness of potentially life‐threatening complications with metformin exposure is an important addition to the veterinary literature.

Hypoglycemia in noncritically ill patients receiving total parenteral nutrition: a multicenter study. (Study group on the problem of hyperglycemia in parenteral nutrition; Nutrition area of the Spanish Society of Endocrinology and Nutrition).

Science.gov (United States)

Olveira, Gabriel; Tapia, María José; Ocón, Julia; Cabrejas-Gómez, Carmen; Ballesteros-Pomar, María D; Vidal-Casariego, Alfonso; Arraiza-Irigoyen, Carmen; Olivares, Josefina; Conde-García, Maria Carmen; García-Manzanares, Álvaro; Botella-Romero, Francisco; Quílez-Toboso, Rosa P; Matía, Pilar; Rubio, Miguel Ángel; Chicharro, Luisa; Burgos, Rosa; Pujante, Pedro; Ferrer, Mercedes; Zugasti, Ana; Petrina, Estrella; Manjón, Laura; Diéguez, Marta; Carrera, Ma José; Vila-Bundo, Anna; Urgelés, Juan Ramón; Aragón-Valera, Carmen; Sánchez-Vilar, Olga; Bretón, Irene; García-Peris, Pilar; Muñoz-Garach, Araceli; Márquez, Efren; Del Olmo, Dolores; Pereira, José Luis; Tous, María C

2015-01-01

Hypoglycemia is a common problem among hospitalized patients. Treatment of hyperglycemia with insulin is potentially associated with an increased risk for hypoglycemia. The aim of this study was to determine the prevalence and predictors of hypoglycemia (capillary blood glucose parenteral nutrition (TPN). This prospective multicenter study involved 19 Spanish hospitals. Noncritically ill adults who were prescribed TPN were included, thus enabling us to collect data on capillary blood glucose and insulin dosage. The study included 605 patients of whom 6.8% (n = 41) had at least one capillary blood glucose <70 mg/dL and 2.6% (n = 16) had symptomatic hypoglycemia. The total number of hypoglycemic episodes per 100 d of TPN was 0.82. In univariate analysis, hypoglycemia was significantly associated with the presence of diabetes, a lower body mass index (BMI), and treatment with intravenous (IV) insulin. Patients with hypoglycemia also had a significantly longer hospital length of stay, PN duration, higher blood glucose variability, and a higher insulin dose. Multiple logistic regression analysis showed that a lower BMI, high blood glucose variability, and TPN duration were risk factors for hypoglycemia. Use of IV insulin and blood glucose variability were predictors of symptomatic hypoglycemia. The occurrence of hypoglycemia in noncritically ill patients receiving PN is low. A lower BMI and a greater blood glucose variability and TPN duration are factors associated with the risk for hypoglycemia. IV insulin and glucose variability were predictors of symptomatic hypoglycemia. Copyright © 2015 Elsevier Inc. All rights reserved.

Severe Hypoglycemia due to Isolated ACTH Deficiency in Children: A New Case Report and Review of the Literature

OpenAIRE

Torchinsky, Michael Y.; Wineman, Robert; Moll, George W.

2011-01-01

Isolated ACTH deficiency causes life-threatening severe hypoglycemia. A 7-year-old girl with hypoglycemia due to this rare disorder is described. Our patient had undetectable plasma ACTH repeatedly and cortisol 0 mcg/dl before and after ACTH 1-24 stimulation. There was no evidence of other pituitary hormone deficiency. Glucocorticoid replacement therapy resulted in resolution of all symptoms and normalization of blood glucose. Previously published data on isolated ACTH deficiency in children ...

Recurrent Hypoglycemia in a Patient with Hodgkin’s Lymphoma: A Case Report with Review of Literature

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Rawal Gautam

2016-09-01

Full Text Available A rare complication associated with the Hodgkin’s lymphoma is the occurrence of persistent or recurrent hypoglycemia. Although few cases have been reported in the literature, describing its pathophysiology to be multifactorial, it is difficult to determine the exact cause. We present the case of a 26 year old patient diagnosed with Hodgkin’s lymphoma who developed recurrent episodes of hypoglycemia and also discuss the various causes for its pathogenesis. In this case the serum insulin and C-peptide levels were found to be low, suggesting the presence of insulin like growth factors (IGF secreted by the cancer cells. Also, we performed a18F-2-fluoro-2-deoxy-d-glucose positron emission tomography that showed a massive tumor load. The published reports in literature have similary suggested the presence of IGF or auto-antibodies secreted by the tumor cells and also the Warburg effect in patients with high tumor load. Further research is required to clearly diagnose and define the exact etiopathogenesis of the hypoglycemia occurring in a patient with Hodgkin’s lymphoma.

Impact of genetic polymorphism in the β₂-receptor gene on risk of severe hypoglycemia in patients with type 1 diabetes

DEFF Research Database (Denmark)

Rokamp, Kim Zillo; Olsen, Niels Vidiendal; Færch, Louise

2018-01-01

characterized by diabetes history, state of hypoglycemia awareness (Clarke, Gold, and Hillerød methods), C-peptide status, hemoglobin A1c (HbA1c), and ADRB2 genotype. Results: The ADRB2 Gly16Arg genotype distribution was in Hardy-Weinberg equilibrium. There was a difference in rate of severe hypoglycemia...

Pancreatic arterial calcium stimulation in the diagnosis and localisation of persistent hyperinsulinemic hypoglycaemia of infancy

Energy Technology Data Exchange (ETDEWEB)

Chigot, V.; Brunelle, F. [Department of Radiology, Hopital des Enfants Malades, Paris (France); Lonlay, P. de; Nassogne, M.-C.; Delagne, V.; Saudubray, J.-M. [Dept. of Paediatrics, Hopital des Enfants Malades, Paris (France); Laborde, K. [Dept. of Biology, Hopital des Enfants Malades, Paris (France); Fournet, J.-C. [Dept. of Pathology, Hopital des Enfants Malades, Paris (France); Nihoul-Fekete, C. [Department of Surgery, Hopital des Enfants Malades, Paris (France)

2001-09-01

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is often resistant to medical therapy. Surgery is therefore necessary. It is due to focal adenomatous islet-cell hyperplasia treatable by partial pancreatectomy, or diffuse beta-cell hyperfunction, which requires near-total pancreatectomy. Pancreatic venous sampling (PVS) is the reference technique for the preoperative diagnosis and localization of focal forms of PHHI in the pancreas. However, hypoglycaemia is necessary to analyse the results and PVS is technically challenging. Pancreatic arterial calcium stimulation (PACS) is technically easier and does not require hypoglycaemia. To study the accuracy in the diagnosis and localization of PHHI. Materials and methods: PACS was performed in 12 patients and correlated with histology. The accuracy of PACS is poor in diffuse lesions since only two of six cases were correctly identified by this test. Five of six focal lesions were correctly recognized and located. PACS is less accurate than PVS in PHHI. Currently, it should be performed only when PVS fails. (orig.)

Pancreatic arterial calcium stimulation in the diagnosis and localisation of persistent hyperinsulinemic hypoglycaemia of infancy

International Nuclear Information System (INIS)

Chigot, V.; Brunelle, F.; Lonlay, P. de; Nassogne, M.-C.; Delagne, V.; Saudubray, J.-M.; Laborde, K.; Fournet, J.-C.; Nihoul-Fekete, C.

2001-01-01

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is often resistant to medical therapy. Surgery is therefore necessary. It is due to focal adenomatous islet-cell hyperplasia treatable by partial pancreatectomy, or diffuse beta-cell hyperfunction, which requires near-total pancreatectomy. Pancreatic venous sampling (PVS) is the reference technique for the preoperative diagnosis and localization of focal forms of PHHI in the pancreas. However, hypoglycaemia is necessary to analyse the results and PVS is technically challenging. Pancreatic arterial calcium stimulation (PACS) is technically easier and does not require hypoglycaemia. To study the accuracy in the diagnosis and localization of PHHI. Materials and methods: PACS was performed in 12 patients and correlated with histology. The accuracy of PACS is poor in diffuse lesions since only two of six cases were correctly identified by this test. Five of six focal lesions were correctly recognized and located. PACS is less accurate than PVS in PHHI. Currently, it should be performed only when PVS fails. (orig.)

Noninsulinoma pancreatogenous hypoglycemia syndrome in a Saudi male

International Nuclear Information System (INIS)

Karawagh, Abullah M.; Gasim, Abdelhamid M.; Abdelaziz, Muntasir M.; Abdullah, Layla S.

2008-01-01

Nesidioblastosis is focal or diffuse islet hyperplasia leading tohyperinsulinism with subsequent hypoglycemia in the absence of insulinoma,usually described in neonates and infancy. We described the first adult caseof nesidioblastosis in Saudi Arabia and the Gulf region. The diagnosis andtreatment of the condition can be very difficult and challenging. Despite thefact that our patient responded initially to surgical treatment, hishypoglycemic symptoms occasionally recurred and needed adjunctive medicaltreatment. Although initially thought to affect only infants and children,cases of nesidioblastosis can effect adults and pose a diagnostic andtherapeutic challenge to the clinicians. (author)

MRI findings of brain damage due to neonatal hypoglycemia

International Nuclear Information System (INIS)

Wang Lu; Fan Guoguang; Ji Xu; Sun Baohai; Guo Qiyong

2009-01-01

Objective: To report the MRI findings of brain damage observed in neonatal patients who suffered from isolated hypoglycemia and to explore the value of diffusion-weighted imaging(DWI) in early detection of neonatal hypoglycemic brain injury. Methods: Twelve neonates with isolated hypoglycemia (10 of the 12 were diagnosed to suffer from hypoglycemic encephalopathy) were enrolled in this study. They were first scanned at age from 3 days to 10 days with T 1 WI, T 2 WI and DWI(b is 0 s/mm 2 , 1000 s/mm 2 ), and 4 of them were then scanned from 7 days to 10 days following the initial scan. All acquired MR images were retrospectively analysed. Results: First series of DWI images showed distinct hyperintense signal in 11 cases in several areas including bilateral occipital cortex (2 cases), right occipital cortex (1 case), left occipital cortex and subcortical white matter(1 case), bilateral occipital cortex and subcortical white matter (2 cases), bilateral parieto-occipital cortex (2 cases), bilateral parieto-occipital cortex and subcortical white matter(2 cases), the splenium of corpus callosum (4 cases), bilateral corona radiata( 2 cases), left caudate nucleus and globus pallidus (1 case), bilateral thalamus (1 case), bilaterally posterior limb of internal capsule (1 case). In the initial T 1 WI and T 2 WI images, there were subtle hypointensity in the damaged cortical areas (3 cases), hyperintensity in the bilaterally affected occipital cortex( 1 case) on T 1 weighted images, and hyperintensity in the affected cortex and subcortical white matter with poor differentiation on T 2 weighted images. The followed-up MRI of 4 cases showed regional encephalomalacia in the affected occipital lobes(4 cases), slightly hyperintensity on T 2 weighted images in the damaged occipital cortex (2 cases), extensive demyelination (1 case), disappearance of hyperintensity of the splenium of corpus callosum (1 case), and persistent hyperintensity in the splenium of corpus callosum (1 case

Hypoglycemia, S-ACE and ACE genotypes in a Danish nationwide population of children and adolescents with type 1 diabetes

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Johannesen, Jesper; Svensson, Jannet; Bergholdt, Regine

2011-01-01

High S-ACE levels have been shown to predispose to increased risk of hypoglycemia, however; some inconsistency relates to the risk of the ACE genotype. We investigated the association between S-ACE level at diagnosis and ACE genotype to long-term risk of severe hypoglycemia in more than 1000 chil...... children and adolescents with type 1 diabetes being part of the Danish Registry of Childhood diabetes over a 10-yr period....

Accuracy evaluation of a new real-time continuous glucose monitoring algorithm in hypoglycemia

DEFF Research Database (Denmark)

Mahmoudi, Zeinab; Jensen, Morten Hasselstrøm; Johansen, Mette Dencker

2014-01-01

UNLABELLED: Abstract Background: The purpose of this study was to evaluate the performance of a new continuous glucose monitoring (CGM) calibration algorithm and to compare it with the Guardian(®) REAL-Time (RT) (Medtronic Diabetes, Northridge, CA) calibration algorithm in hypoglycemia. SUBJECTS...... AND METHODS: CGM data were obtained from 10 type 1 diabetes patients undergoing insulin-induced hypoglycemia. Data were obtained in two separate sessions using the Guardian RT CGM device. Data from the same CGM sensor were calibrated by two different algorithms: the Guardian RT algorithm and a new calibration...... algorithm. The accuracy of the two algorithms was compared using four performance metrics. RESULTS: The median (mean) of absolute relative deviation in the whole range of plasma glucose was 20.2% (32.1%) for the Guardian RT calibration and 17.4% (25.9%) for the new calibration algorithm. The mean (SD...

Brain glucose transport and phosphorylation under acute insulin-induced hypoglycemia in mice: an 18F-FDG PET study.

Science.gov (United States)

Alf, Malte F; Duarte, João M N; Schibli, Roger; Gruetter, Rolf; Krämer, Stefanie D

2013-12-01

We addressed the questions of how cerebral glucose transport and phosphorylation change under acute hypoglycemia and what the underlying mechanisms of adaptation are. Quantitative (18)F-FDG PET combined with the acquisition of real-time arterial input function was performed on mice. Hypoglycemia was induced and maintained by insulin infusion. PET data were analyzed with the 2-tissue-compartment model for (18)F-FDG, and the results were evaluated with Michaelis-Menten saturation kinetics. Glucose clearance from plasma to brain (K1,glc) and the phosphorylation rate constant increased with decreasing plasma glucose (Gp), in particular at a Gp of less than 2.5 mmol/L. Estimated cerebral glucose extraction ratios taking into account an increased cerebral blood flow (CBF) at a Gp of less than 2 mmol/L were between 0.14 and 0.79. CBF-normalized K1,glc values were in agreement with saturation kinetics. Phosphorylation rate constants indicated intracellular glucose depletion at a Gp of less than 2-3 mmol/L. When brain regions were compared, glucose transport under hypoglycemia was lowest in the hypothalamus. Alterations in glucose transport and phosphorylation, as well as intracellular glucose depletion, under acute hypoglycemia can be modeled by saturation kinetics taking into account an increase in CBF. Distinct transport kinetics in the hypothalamus may be involved in its glucose-sensing function.

Presentations for hypoglycemia associated with diabetes mellitus to emergency departments in a Canadian province: A database and epidemiological analysis.

Science.gov (United States)

Alexiu, Chris J; Chuck, Anderson; Jelinski, Susan E; Rowe, Brian H

2017-08-01

The prevalence of diabetes mellitus was reportedly 9% in 2014, making it one of the most common global chronic conditions. Hypoglycemia is an important complication of diabetes treatment. The objective of this study was to quantify and characterize hypoglycemia presentations associated with type 1 or 2 diabetes made to emergency departments (EDs) by adults in a Canadian province. A retrospective cohort study was conducted using reliable administrative data from Alberta for a five-year period (2010/11-2014/15). Records of interest were those with an ICD-10-CA diagnosis of diabetes-associated hypoglycemia (e.g., E10.63). A descriptive analysis was conducted. Data extraction yielded 7835 presentations by 5884 patients. The majority (56.2%) of presentations were made by males, median patient age was 62, and 60.5% had type 2 diabetes. These episodes constituted 0.08% of presentations to Alberta EDs. The annual rate of presentations decreased by 11.8% during the five-year period. Most presentations (63.4%) involved transportation to ED via ambulance. Median length-of-stay was four hours. For 27.5% of presentations, an X-ray was obtained. Most hypoglycemic episodes (65.2%) were considered to be moderate, while 34.3% were considered to be severe. Diabetes-associated hypoglycemia presentations to Alberta EDs are more commonly made by patients with type 2 diabetes, who are more likely to be transported via ambulance and also admitted. Each year, approximately one percent of Albertans with diabetes presented with a hypoglycemia episode; however, knowledge of the variation across regions can guide a strategy for improved care. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-severe Hypoglycemia Risk Difference between Sulfonylurea and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2-I) as an Add-On to Metformin in Randomized Controlled Trials.

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Farahani, Pendar

2017-05-23

Non-severe hypoglycemia reduces well-being, lowers quality of life, reduces productivity and increases treatment costs. The non-severe hypoglycemia rate, attributable to sulfonylurea (SU) utilization compared with newer classes such as SGLT2-I, could be of clinical significance. To explore the non-severe hypoglycemia risk difference (RD) for SU use compared with SGLT2-I in randomized controlled trials (RCTs) as an add on to metformin. A search was conducted for RCTs of SGLT2-I. PubMed database were utilized for this search. The search was limited to RCTs reported in English language for canagliflozin, dapagliflozin, and empagliflozin. SU dose comparison was utilized to convert the dose of SUs to glimepiride equivalent doses. Totally, 118 RCTs were reviewed; 6 articles had an arm for a SU as add on to metformin. Six articles belong to 3 RCTs, which reported results for 52 weeks and 104 weeks. Average non-severe hypoglycemia rate for SU arm was 30% (5.5%) [Mean (SD)] for 52 weeks and 35.6% (6.1%) for 104 weeks. RD for non-severe hypoglycemia events for SU compared to SGLT2-I was 26.7% (4.9%) for 52 weeks (p-value less than 0.001) and 30.6% (5.5%) for 104 weeks (p-value less than 0.001). There was a significant correlation between dose of SU and hypoglycemia rate (Pearson correlation 0.995; R-square 99%). This study illustrated that a large proportion of patients who had exposure to SU in RCTs of SGLT2-I experienced non-severe hypoglycemia compared to SGLT2-I. There was a close relation between SU dose and increased probability of non-severe hypoglycemia events. © 2017 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.

Accuracy of a cow-side test for the diagnosis of hyperketonemia and hypoglycemia in lactating dairy cows.

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Macmillan, K; López Helguera, I; Behrouzi, A; Gobikrushanth, M; Hoff, B; Colazo, M G

2017-12-01

The objective of this study was to evaluate the use of a cow-side device (FreeStyle Precision Neo™) to diagnose ketosis and hypoglycemia based on measures of blood β-hydroxybutyrate (BHBA) and glucose. Eleven commercial dairy farms were visited and blood samples were taken from Holstein cows between 2 and 14days in milk, yielding 441 samples for BHBA analysis and 308 samples for glucose analysis. Concentrations of BHBA and glucose were measured in two ways, 1) using the cow-side device with whole blood immediately after sampling and 2) serum samples analyzed with a standard laboratory assay (Animal Health Laboratory, University of Guelph, Canada). The accuracy of the device was determined by comparing the results to the laboratory method as well as the ability to diagnose ketosis (BHBA ≥1.2mmol/L) and hypoglycemia (glucose cow-side device is accurate for rapid measurement of blood BHBA and diagnosis of ketosis on farms but is not accurate for measurement of blood glucose concentrations and diagnosis of hypoglycemia. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Frequency and risk factors of severe hypoglycemia in insulin-treated type 2 diabetes

DEFF Research Database (Denmark)

Akram, Kamran; Pedersen-Bjergaard, Ulrik; Borch-Johnsen, Knut

2006-01-01

Intensive treatment regimens including early initiation of insulin treatment are important to prevent late complications in type 2 diabetes. The assumed risk of severe hypoglycemia (SH) is a major barrier to initiation of insulin treatment. To assess the relevance of this risk we evaluated...... the frequency of SH as reported in the literature. Using Medline and Embase search we identified 11 studies (5 retrospective and 6 prospective) including at least 50 patients with insulin-treated type 2 diabetes followed for at least 6 months in which frequency of SH was reported. The incidence of SH....... Only few studies looked into the impact of risk factors on the rate of SH. Impaired hypoglycemia awareness, high age, long duration of diabetes and insulin therapy increased the risk, while no association was found with HbA1c and insulin dose. The present knowledge of SH in insulin-treated type 2...

The Influence of New European Union Driver’s License Legislation on Reporting of Severe Hypoglycemia by Patients With Type 1 Diabetes

DEFF Research Database (Denmark)

Pedersen-Bjergaard, Ulrik; Færch, Louise; Allingbjerg, Marie-Louise

2015-01-01

OBJECTIVE: We test the hypotheses that the implementation in Denmark of new, stricter European Union (EU) legislation on driver's licensing, with the purpose to improve traffic safety in January 2012, has reduced the self-reported rate of severe hypoglycemia in a routine clinical setting...... of concealed severe hypoglycemia may impair the safety of affected patients and unintentionally paradoxically reduce the general traffic safety....

Severe Hypoglycemia Is a Serious Complication and Becoming an Economic Burden in Diabetes

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Won Chul Ha

2012-08-01

Full Text Available BackgroundThe prevalence of hypoglycemia is increasing due to the growing incidence of diabetes and the latest strict guidelines for glycated hemoglobin (HbA1c levels under 7%. This study examined the clinical characteristics, causal factors, and medical costs of severely hypoglycemic patients in an emergency room (ER of Uijeongbu St. Mary's Hospital.MethodsThe study consisted of a retrospective analysis of the characteristics, risk factors, and medical costs of 320 severely hypoglycemic patients with diabetes who presented to an ER of Uijeongbu St. Mary's Hospital from January 1, 2006 to December 31, 2009.ResultsMost hypoglycemic patients (87.5%, 280/320 were over 60 years old with a mean age of 69.5±10.9 years and a mean HbA1c level of 6.95±1.46%. Mean serum glucose as noted in the ER was 37.9±34.5 mg/dL. Renal function was decreased, serum creatinine was 2.0±2.1 mg/dL and estimated glomerular filtration rate (eGFR was 48.0±33.6 mL/min/1.73 m2. In addition, hypoglycemic patients typically were taking sulfonylureas or insulin and a variety of other medications, and had a long history of diabetes.ConclusionSevere hypoglycemia is frequent in older diabetic patients, subjects with low HbA1c levels, and nephropathic patients. Therefore, personalized attention is warranted, especially in long-term diabetics with multiple comorbidities who may not have been properly educated or may need re-education for hypoglycemia.

Prevalence and predictors of severe hypoglycemia in Danish children and adolescents with diabetes

DEFF Research Database (Denmark)

Johansen, Anders; Kanijo, B; Fredheim, S

2015-01-01

OBJECTIVE: To investigate the prevalence of severe hypoglycemia in Danish children and adolescents with type 1 diabetes and to pinpoint predictors of this acute complication in children on modern treatment modalities. RESEARCH DESIGN AND METHODS: The study is based on data from DanDiabKids...

Changes of cognition and regional cerebral activity during acute hypoglycemia in normal subjects

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Bie-Olsen, Lise G; Kjaer, Troels W; Pedersen-Bjergaard, Ulrik

2009-01-01

cerebral blood flow (rCBF) as a marker of cerebral activity. Hypoglycemia was induced by intravenous insulin infusion in 19 healthy men performing two different cognitive tasks of varying complexity. The hypoglycemic stimulus [plasma glucose 2.2 mmol/liter (0.4)] produced a significant hormonal...

Hypoglycemia in type 2 diabetes patients treated with insulin: the advantages of continuous glucose monitoring

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Vadim Valer'evich Klimontov

2014-03-01

Full Text Available Aims.  To determine the incidence and risk factors for hypoglycemia in elderly insulin-treated type 2 diabetes mellitus (T2DM patients by means of continuous glucose monitoring (CGM. Materials and Methods.  We observed seventy-six hospitalized patients with T2DM, aged 65 to 79 years. Treatment with basal insulin (n=36, premixed insulin (n=12 or basal-bolus insulin regimen (n=28 was followed by metformin (n=44, glimepiride (n=14 and dipeptidyl peptidase-4 inhibitors (n=14. 2-days CGM with retrospective data analysis was performed in all patients. During CGM, three fasting and three 2-h postprandial finger-prick glucose values were obtained daily with portable glucose meter. Results.  Hypoglycemia (identified as blood glucose

Generalized Anxiety Disorder and Hypoglycemia Symptoms Improved with Diet Modification

OpenAIRE

Aucoin, Monique; Bhardwaj, Sukriti

2016-01-01

Observational evidence suggests that a relationship may exist between high glycemic index diets and the development of anxiety and depression symptoms; however, as no interventional studies assessing this relationship in a psychiatric population have been completed, the possibility of a causal link is unclear. AB is a 15-year-old female who presented with concerns of generalized anxiety disorder and hypoglycemia symptoms. Her diet consisted primarily of refined carbohydrates. The addition of ...

Insulinoma: A rare cause of hypoglycemia in a young female

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Fnu Kelash

2014-09-01

Full Text Available Insulinoma is an exceedingly uncommon pancreatic islet cell neuroendocrine tumor. The estimated incidence is approximately four cases per million individuals per year and accounts for 60% of islets cell tumors. It causes glycopenic symptoms which includes headache, feeling irritable, confused, seizure or coma and leads to catecholamine excess which includes rapid heartbeat, sweating, palpitations and feelings of hunger. Early detection of the tumor prevents recurrent episodes of lethal hypoglycemia.

Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy.

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Tam, Emily W Y; Haeusslein, Laurel A; Bonifacio, Sonia L; Glass, Hannah C; Rogers, Elizabeth E; Jeremy, Rita J; Barkovich, A James; Ferriero, Donna M

2012-07-01

To investigate the contribution of hypoglycemia in the first 24 hours after birth to brain injury in term newborns at risk for neonatal encephalopathy. A prospective cohort of 94 term neonates born between 1994 and 2010 with early postnatal brain magnetic resonance imaging studies were analyzed for regions of brain injury. Neurodevelopmental outcome was assessed at 1 year of age. Hypoglycemia (glucose encephalopathy with increased corticospinal tract injury and adverse motor and cognitive outcomes. Copyright © 2012 Mosby, Inc. All rights reserved.

No hypoglycemia after subcutaneous administration of glucagon-like peptide-1 in lean type 2 diabetic patients and in patients with diabetes secondary to chronic pancreatitis

DEFF Research Database (Denmark)

Knop, Filip K; Vilsbøll, Tina; Larsen, Steen

2003-01-01

administration of GLP-1 concomitant with intravenous glucose results in hypoglycemia in healthy subjects. Because GLP-1 is also effective in type 2 diabetic patients and is currently being evaluated as a therapeutic agent, it is important to investigate whether GLP-1 may cause hypoglycemia in such patients. We...... have previously shown that GLP-1 does not cause hypoglycemia in obese type 2 diabetic patients with insulin resistance amounting to 5.4 +/- 1.1 according to homeostasis model assessment (HOMA). In this study, we investigated diabetic patients with normal or close to normal insulin sensitivity....

Glycemic Control, Self-Efficacy and Fear of Hypoglycemia Among Iranian Children with Type 1 Diabetes.

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Amiri, Fatemehsadat; Vafa, Mohammadreza; Gonder-Frederick, Linda

2015-08-01

This study was designed to test the reliability of a Persian version of 2 questionnaires to assess the level of fear of hypoglycemia (FoH) and self-efficacy in diabetes management and their association with glycated hemoglobin (A1C) and parents' demographic characteristics in a sample of children with type 1 diabetes. We assessed 61 children with type 1 diabetes (35 boys and girls, 6.0 to 12.7 years of age) using the Hypoglycemia Fear Survey-Child version (HFS-C) and Self-Efficacy for Diabetes Scale-Child version (SED-C). Their glycemic control was evaluated by A1C levels. The internal consistency of the Persian version of HFS-C and SED-C were very good. Our results showed that children older than 10 years of age report lower levels of FoH, which are related to higher levels of self-efficacy (r=-.30, p=0.025 and r=-.30, p=0.02, respectively). Of the children, 42.3% of girls and 31.4% of boys reported that low blood sugar is a big problem for them. These findings suggest that FoH is a significant concern for this target group. Only 19.7% of children had controlled diabetes based on A1C levels. There was no significant association between higher A1C levels and other variables, including HFS-C, SED-C and parents' demographic characteristics. The Persian version of HFS-C and SED-C are reliable and valid measures of the fear of hypoglycemia and of self-efficacy in children with type 1 diabetes, and these questionnaires could be used in our country for identifying those children who may need diabetes education and other supports. The association between greater self-efficacy and lower fear of hypoglycemia suggests that addressing self-efficacy in diabetes education courses may be effective in helping to overcome FoH. Copyright © 2015 Canadian Diabetes Association. All rights reserved.

Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function.

Science.gov (United States)

Altuntas, Yuksel; Bilir, Muammer; Ucak, Sema; Gundogdu, Sadi

2005-04-01

Reactive hypoglycemia (RH), which is a postprandial hypoglycemic state, occurs within 2-5 h after food intake. It is classified as idiopathic, alimentary, or diabetic reactive hypoglycemia. We studied the incidence of reactive hypoglycemia and looked for any correlations between it and the presence of insulin sensitivity and/or beta cell function in young lean polycystic ovary syndrome (PCOS) patients. This study was designed as a cross-sectional study in 64 lean young women with PCOS (BMI lean young women with PCOS. DHEA-S and PRL levels were found to be lower in subjects with RH (P 0.05, respectively). Beta cell function indices such as the insulinogenic index (at 120 min), CIR (at 120 min) and HOMA beta cell index were found to be insignificantly higher in the RH group than the nonreactive hypoglycemia (NRH) group. The 4 h glucose level, but not the 3 h glucose level, was significantly correlated with insulin resistance indices, such as fasting insulin level, HOMA-IR, Quicky index, and FIRI in the RH group. Significantly decreased DHEA-S levels were an interesting finding. In conclusion, there is an urgent need to investigate RH in lean young women with PCOS. Our results indicate that more definite insulin resistance occurs in subjects with RH in the fourth hour of the OGTT than those with RH in the third hour. In addition, RH in the fourth hour together with a low DHEA-S level may be predictive of future diabetes in young women with PCOS even when they are not obese.

The GOAT-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction.

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Chun-Xia Yi

Full Text Available Ghrelin acylation by ghrelin O-acyltransferase (GOAT has recently been reported to be essential for the prevention of hypoglycemia during prolonged negative energy balance. Using a unique set of four different genetic loss-of-function models for the GOAT/ghrelin/growth hormone secretagogue receptor (GHSR system, we thoroughly tested the hypothesis that lack-of-ghrelin activation or signaling would lead to hypoglycemia during caloric deprivation.Male and female knockout (KO mice for GOAT, ghrelin, GHSR, or both ghrelin and GHSR (dKO were subjected to prolonged calorie restriction (40% of ad libitum chow intake. Body weight, fat mass, and glucose levels were recorded daily and compared to wildtype (WT controls. Forty-eight hour blood glucose profiles were generated for each individual mouse when 2% or less body fat mass was reached. Blood samples were obtained for analysis of circulating levels of acyl- and desacyl-ghrelin, IGF-1, and insulin.Chronic calorie restriction progressively decreased body weight and body fat mass in all mice regardless of genotype. When fat mass was depleted to 2% or less of body weight for 2 consecutive days, random hypoglycemic events occurred in some mice across all genotypes. There was no increase in the incidence of hypoglycemia in any of the four loss-of-function models for ghrelin signaling including GOAT KO mice. Furthermore, no differences in insulin or IGF-1 levels were observed between genotypes.The endogenous GOAT-ghrelin-GHSR system is not essential for the maintenance of euglycemia during prolonged calorie restriction.

Diabetic emergencies including hypoglycemia during Ramadan

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Jamal Ahmad

2012-01-01

Full Text Available Majority of physicians are of the opinion that Ramadan fasting is acceptable for well-balanced type 2 patients conscious of their disease and compliant with their diet and drug intake. Fasting during Ramadan for patients with diabetes carries a risk of an assortment of complications. Islamic rules allow patients not to fast. However, if patient with diabetes wish to fast, it is necessary to advice them to undertake regular monitoring of blood glucose levels several times a day, to reduce the risk of hypoglycemia during day time fasting or hyperglycemia during the night. Patient with type 1 diabetes who fast during Ramadan may be better managed with fast-acting insulin. They should have basic knowledge of carbohydrate metabolism, the standard principles of diabetes care, and pharmacology of various antidiabetic drugs. This Consensus Statement describes the management of the various diabetic emergencies that may occur during Ramadan.

Diabetic emergencies including hypoglycemia during Ramadan

Science.gov (United States)

Ahmad, Jamal; Pathan, Md Faruque; Jaleel, Mohammed Abdul; Fathima, Farah Naaz; Raza, Syed Abbas; Khan, A. K. Azad; Ishtiaq, Osama; Sheikh, Aisha

2012-01-01

Majority of physicians are of the opinion that Ramadan fasting is acceptable for well-balanced type 2 patients conscious of their disease and compliant with their diet and drug intake. Fasting during Ramadan for patients with diabetes carries a risk of an assortment of complications. Islamic rules allow patients not to fast. However, if patient with diabetes wish to fast, it is necessary to advice them to undertake regular monitoring of blood glucose levels several times a day, to reduce the risk of hypoglycemia during day time fasting or hyperglycemia during the night. Patient with type 1 diabetes who fast during Ramadan may be better managed with fast-acting insulin. They should have basic knowledge of carbohydrate metabolism, the standard principles of diabetes care, and pharmacology of various antidiabetic drugs. This Consensus Statement describes the management of the various diabetic emergencies that may occur during Ramadan. PMID:22837906

Intensive Individualized Reinforcement Education Is Important for the Prevention of Hypoglycemia in Patients with Type 2 Diabetes

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Yun-Mi Yong

2015-04-01

Full Text Available BackgroundWe investigated whether an intensive individualized reinforcement education program could influence the prevention of hypoglycemic events in patients with type 2 diabetes.MethodsFrom March 2013 to September 2013, patients aged 35 to 75 years with type 2 diabetes who had not previously participated in diabetes education, and treated with insulin or a sulfonylurea-containing regimen were included in the study. After structured group education, the patients assigned to the intensive individualized education group (IT were requested to visit for reinforcement. All subjects in the IT were encouraged to self-manage dose adjustments. Participants in both groups (control group [CG, group education only; n=22] and IT [n=24] attended follow-up visits at 2, 8, 12, and 24 weeks. At each visit, all patients were asked whether they had experienced hypoglycemia.ResultsThe total study population consisted of 20 men (43.5%; mean age and diabetic duration of 55.9±11.0 and 5.1±7.3 years, respectively. At 24 weeks, there were no significant differences in hemoglobin A1c values between the CG and IT. The total number of hypoglycemic events per patient was 5.26±6.5 in the CG and 2.58±2.3 times in the IT (P=0.004. Adherence to lifestyle modification including frequency of exercise, self-monitoring of blood glucose, or dietary habit was not significantly different between the groups. However, adherence to hypoglycemia management, especially the dose adjustment of medication, was significantly higher in the IT compared with the CG.ConclusionCompared with the structured group education, additional IT resulted in additional benefits in terms of avoidance of hypoglycemia and treating hypoglycemia in patients with type 2 diabetes.

Intensive individualized reinforcement education is important for the prevention of hypoglycemia in patients with type 2 diabetes.

Science.gov (United States)

Yong, Yun-Mi; Shin, Kyung-Mi; Lee, Kang-Min; Cho, Jae-Young; Ko, Sun-Hye; Yoon, Min-Hyang; Kim, Tae-Won; Jeong, Jong-Hyun; Park, Yong-Moon; Ko, Seung-Hyun; Ahn, Yu-Bae

2015-04-01

We investigated whether an intensive individualized reinforcement education program could influence the prevention of hypoglycemic events in patients with type 2 diabetes. From March 2013 to September 2013, patients aged 35 to 75 years with type 2 diabetes who had not previously participated in diabetes education, and treated with insulin or a sulfonylurea-containing regimen were included in the study. After structured group education, the patients assigned to the intensive individualized education group (IT) were requested to visit for reinforcement. All subjects in the IT were encouraged to self-manage dose adjustments. Participants in both groups (control group [CG, group education only; n=22] and IT [n=24]) attended follow-up visits at 2, 8, 12, and 24 weeks. At each visit, all patients were asked whether they had experienced hypoglycemia. The total study population consisted of 20 men (43.5%; mean age and diabetic duration of 55.9±11.0 and 5.1±7.3 years, respectively). At 24 weeks, there were no significant differences in hemoglobin A1c values between the CG and IT. The total number of hypoglycemic events per patient was 5.26±6.5 in the CG and 2.58±2.3 times in the IT (P=0.004). Adherence to lifestyle modification including frequency of exercise, self-monitoring of blood glucose, or dietary habit was not significantly different between the groups. However, adherence to hypoglycemia management, especially the dose adjustment of medication, was significantly higher in the IT compared with the CG. Compared with the structured group education, additional IT resulted in additional benefits in terms of avoidance of hypoglycemia and treating hypoglycemia in patients with type 2 diabetes.

Effect of fasting ramadan in diabetes control status - application of extensive diabetes education, serum creatinine with HbA1c statistical ANOVA and regression models to prevent hypoglycemia.

Science.gov (United States)

Aziz, Kamran M A

2013-09-01

Ramadan fasting is an obligatory duty for Muslims. Unique physiologic and metabolic changes occur during fasting which requires adjustments of diabetes medications. Although challenging, successful fasting can be accomplished if pre-Ramadan extensive education is provided to the patients. Current research was conducted to study effective Ramadan fasting with different OHAs/insulins without significant risk of hypoglycemia in terms of HbA1c reductions after Ramadan. ANOVA model was used to assess HbA1c levels among different education statuses. Serum creatinine was used to measure renal functions. Pre-Ramadan diabetes education with alteration of therapy and dosage adjustments for OHAs/insulin was done. Regression models for HbA1c before Ramadan with FBS before sunset were also synthesized as a tool to prevent hypoglycemia and successful Ramadan fasting in future. Out of 1046 patients, 998 patients fasted successfully without any episodes of hypoglycemia. 48 patients (4.58%) experienced hypoglycemia. Χ(2) Test for CRD/CKD with hypoglycemia was also significant (p-value Ramadan diabetes management. Some relevant patents are also outlined in this paper.

Blood glucose response to rescue dextrose in hypoglycemic, critically ill patients receiving an insulin infusion.

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Murthy, Manasa S; Duby, Jeremiah J; Parker, Patricia L; Durbin-Johnson, Blythe P; Roach, Denise M; Louie, Erin L

2015-08-01

There is inadequate guidance for clinicians on selection of the optimal dextrose 50% (D50W) dose for hypoglycemia correction in critically ill patients. The purpose of this study was to determine the blood glucose (BG) response to D50W in critically ill patients. A retrospective analysis was conducted of critically ill patients who received D50W for hypoglycemia (BG 150 mg/dL), resulting in a 6.8% rate of overcorrection; 49% of hypoglycemic episodes (230/470) corrected to a BG >100 mg/dL. A multivariable GEE analysis showed a significantly higher BG response in participants with diabetes (0.002) but a lower response in those with recurrent hypoglycemia (P = 0.049). The response to D50W increased with increasinginsulin infusion rate (P = 0.022). Burn patients experienced a significantly larger BG response compared with cardiac, medical, neurosurgical, or surgical patients. The observed median effect of D50W on BG was approximately 4 mg/dL per gram of D50W administered. Application of these data may aid in rescue protocol development that may reduce glucose variability associated with hypoglycemic episodes and the correction. © The Author(s) 2015.

The impact of eating behavior on psychological symptoms typical of reactive hypoglycemia. A pilot study comparing women with polycystic ovary syndrome to controls.

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Barry, John A; Bouloux, Pierre; Hardiman, Paul J

2011-08-01

The idea that diet can affect mood and behavior in women with polycystic ovary syndrome (PCOS) by altering blood glucose levels has become popular in recent years. This paper describes an online survey (N=462) of 24 women with PCOS, 299 healthy control women, 47 women who possibly had undiagnosed PCOS, and 92 men. The groups were compared for symptoms of mood and behavioral symptoms typical of reactive (postprandial) hypoglycemia. The outcome measures were two questionnaires that measure states associated with hypoglycemia: the Hypoglycemia Symptom Checklist-7 (HSC-7), which measures behavioral symptoms and the Mood Adjective Checklist (MACL), which measures emotional states. Controlling for age and body mass index (BMI) using between-groups analysis of covariance (ANCOVA), the women with PCOS scored significantly higher than the other three groups (pPCOS compared to twelve healthy control women closely matched for age, BMI, and eating behavior. The findings are suggestive of hypoglycemia-related mood and behavioral problems in PCOS. Future research should test whether blood glucose levels correlate with these symptoms in PCOS, and whether a low glycemic index ('low-GI') diet improves the symptoms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Trends in Drug Utilization, Glycemic Control, and Rates of Severe Hypoglycemia, 2006-2013.

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Lipska, Kasia J; Yao, Xiaoxi; Herrin, Jeph; McCoy, Rozalina G; Ross, Joseph S; Steinman, Michael A; Inzucchi, Silvio E; Gill, Thomas M; Krumholz, Harlan M; Shah, Nilay D

2017-04-01

To examine temporal trends in utilization of glucose-lowering medications, glycemic control, and rate of severe hypoglycemia among patients with type 2 diabetes (T2DM). Using claims data from 1.66 million privately insured and Medicare Advantage patients with T2DM from 2006 to 2013, we estimated the annual 1 ) age- and sex-standardized proportion of patients who filled each class of agents; 2 ) age-, sex-, race-, and region-standardized proportion with hemoglobin A 1c (HbA 1c ) use increased for metformin (from 47.6 to 53.5%), dipeptidyl peptidase 4 inhibitors (0.5 to 14.9%), and insulin (17.1 to 23.0%) but declined for sulfonylureas (38.8 to 30.8%) and thiazolidinediones (28.5 to 5.6%; all P use of glucose-lowering drugs has changed dramatically among patients with T2DM. Overall glycemic control has not improved and remains poor among nearly a quarter of the youngest patients. The overall rate of severe hypoglycemia remains largely unchanged. © 2017 by the American Diabetes Association.

Hematocrit correction does not improve glucose monitor accuracy in the assessment of neonatal hypoglycemia.

Science.gov (United States)

Wang, Li; Sievenpiper, John L; de Souza, Russell J; Thomaz, Michele; Blatz, Susan; Grey, Vijaylaxmi; Fusch, Christoph; Balion, Cynthia

2013-08-01

The lack of accuracy of point of care (POC) glucose monitors has limited their use in the diagnosis of neonatal hypoglycemia. Hematocrit plays an important role in explaining discordant results. The objective of this study was to to assess the effect of hematocrit on the diagnostic performance of Abbott Precision Xceed Pro (PXP) and Nova StatStrip (StatStrip) monitors in neonates. All blood samples ordered for laboratory glucose measurement were analyzed using the PXP and StatStrip and compared with the laboratory analyzer (ABL 800 Blood Gas analyzer [ABL]). Acceptable error targets were ±15% for glucose monitoring and ±5% for diagnosis. A total of 307 samples from 176 neonates were analyzed. Overall, 90% of StatStrip and 75% of PXP values met the 15% error limit and 45% of StatStrip and 32% of PXP values met the 5% error limit. At glucose concentrations ≤4 mmol/L, 83% of StatStrip and 79% of PXP values met the 15% error limit, while 37% of StatStrip and 38% of PXP values met the 5% error limit. Hematocrit explained 7.4% of the difference between the PXP and ABL whereas it accounted for only 0.09% of the difference between the StatStrip and ABL. The ROC analysis showed the screening cut point with the best performance for identifying neonatal hypoglycemia was 3.2 mmol/L for StatStrip and 3.3 mmol/L for PXP. Despite a negligible hematocrit effect for the StatStrip, it did not achieve recommended error limits. The StatStrip and PXP glucose monitors remain suitable only for neonatal hypoglycemia screening with confirmation required from a laboratory analyzer.

Effects of Alcohol on Plasma Glucose and Prevention of Alcohol-induced Hypoglycemia in Type 1 Diabetes - A Systematic Review with GRADE

DEFF Research Database (Denmark)

Tetzschner, R; Nørgaard, K; Ranjan, A

2018-01-01

systematically reviewed the literature for ethanol effects on plasma glucose and for prevention strategies on ethanol-induced hypoglycemia. METHODS: Electronic searches on PubMed and Google were conducted in February 2017. Randomized clinical trials and observational studies were included. Studies involved...... patients with T1D with no history of ethanol abuse. The primary aims were changes in plasma glucose after ethanol intake and prevention strategies for ethanol-induced hypoglycemia. Quality of the studies was assessed by GRADE. Additionally, we searched for guidelines from diabetes associations...

Severe Hypoglycemia due to Isolated ACTH Deficiency in Children: A New Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

Michael Y. Torchinsky

2011-01-01

Full Text Available Isolated ACTH deficiency causes life-threatening severe hypoglycemia. A 7-year-old girl with hypoglycemia due to this rare disorder is described. Our patient had undetectable plasma ACTH repeatedly and cortisol 0 mcg/dl before and after ACTH 1-24 stimulation. There was no evidence of other pituitary hormone deficiency. Glucocorticoid replacement therapy resulted in resolution of all symptoms and normalization of blood glucose. Previously published data on isolated ACTH deficiency in children is summarized. Review of the literature showed that the prevalence of this condition could be underestimated in the neonatal period and in Prader-Willi syndrome. Isolated ACTH deficiency occurs in older children as well as in neonates.

Usefulness of continuous glucose monitoring for the diagnosis of hypoglycemia after a gastric bypass in a patient previously treated for type 2 diabetes.

Science.gov (United States)

Hanaire, Hélène; Dubet, Audrey; Chauveau, Marie-Emilie; Anduze, Yves; Fernandes, Martine; Melki, Vincent; Ritz, Patrick

2010-01-01

Hypoglycemia is rare after a gastric bypass and can be taken for a dumping syndrome. There is no report in the literature of the contribution of continuous glucose monitoring to the diagnosis of hypoglycemia in these circumstances. The present case report shows that continuous glucose monitoring can be a useful tool for the diagnosis and the management of such episodes. Continuous glucose monitoring revealed hypoglycemic episodes in free living circumstances that were not present during 72-h fasting. These episodes followed wide hyperglycemic swings. No such episode resumed over 8 months after specific dietary advices and treatment by 50 mg TID of acarbose. Because hypoglycemia can be difficult to diagnose from dumping syndrome, continuous glucose monitoring is a very useful tool revealing the episodes in free living circumstances and can be used to monitor the treatment success.

Impact of symptomatic hypoglycemia on medication adherence, patient satisfaction with treatment, and glycemic control in patients with type 2 diabetes

Directory of Open Access Journals (Sweden)

Walz L

2014-04-01

Full Text Available Lotta Walz,1,3 Billie Pettersson,2,3 Ulf Rosenqvist,4 Anna Deleskog,3,5 Gunilla Journath,6 Per Wändell7 1Department of Oncology-Pathology, Karolinska Institutet, Stockholm, 2Center for Medical Technology Assessment, Linköping University, Linköping, 3Merck Sharp and Dohme (Sweden AB, Sollentuna, 4Department of Internal Medicine, Motala Hospital, Motala, 5Department of Molecular Medicine and Surgery, 6Department of Medicine, Karolinska Institutet, Stockholm, 7Department of Neurobiology, Care Sciences and Society, Centre for Family Medicine, Karolinska Institutet, Huddinge, Sweden Background: The purpose of this study was to evaluate the impact of symptomatic hypoglycemia on medication adherence, satisfaction with treatment, and glycemic control in patients with type 2 diabetes based on the treatment goals stated in the Swedish national guidelines. Methods: This cross-sectional, multicenter study was carried out between January and August 2009 in 430 consecutive primary health care patients on stable doses of metformin and sulfonylureas for at least 6 months. The patients completed questionnaires covering their experiences of low blood glucose and adherence, as well as barriers to and satisfaction with drug treatment (using the Treatment Satisfaction Questionnaire for Medication. Physicians collected the data from medical records. Results: Patients who experienced moderate or worse symptoms of hypoglycemia reported poorer adherence to medication (46% versus 67%; P<0.01 and were more likely to perceive barriers such as “bothered by medication side effects” (36% versus 14%; P<0.001 compared with patients with no or mild symptoms. Patients with moderate or worse symptoms of hypoglycemia were less satisfied with their treatment than those with no or mild symptoms as determined by the Treatment Satisfaction Questionnaire for Medication-Global satisfaction (67.0 versus 71.2; P<0.05. Overall, achievement of target glycated hemoglobin

The incidence and risk factors associated with developing symptoms of hypoglycemia after bariatric surgery.

Science.gov (United States)

Lee, Clare J; Brown, Todd T; Schweitzer, Michael; Magnuson, Thomas; Clark, Jeanne M

2018-01-31

Hypoglycemia after bariatric surgery is an increasingly recognized metabolic complication associated with exaggerated secretion of insulin and gut hormones. We sought to determine the incidence of hypoglycemic symptoms (hypo-sx) after bariatric surgery and characteristics of those affected compared with those unaffected. University hospital. We collected retrospective survey data from the patients who underwent bariatric surgery at a single center. Based on number and severity of postprandial hypo-sx in Edinburgh hypoglycemia questionnaire postoperatively, patients without preoperative hypo-sx were grouped into high versus low suspicion for hypoglycemia. We used multivariable logistic regression to examine potential baseline and operative risk factors for the development of hypo-sx after surgery. Among the 1119 patients who had undergone bariatric surgery who received the questionnaire, 464 (40.6%) responded. Among the 341 respondents without preexisting hypo-sx, 29% (n = 99) had new-onset hypo-sx, and most were severe cases (n = 92) with neuroglycopenic symptoms. Compared with the low suspicion group, the high suspicion group consisted of more female patients, younger patients, patients without diabetes, and those who underwent Roux-en-Y gastric bypass with a longer time since surgery and more weight loss. In multivariate analysis, factors independently associated with incidence of hypo-sx after bariatric surgery were female sex (P = .003), Roux-en-Y gastric bypass (P = .001), and absence of preexisting diabetes (P = .011). New onset postprandial hypoglycemic symptoms after bariatric surgery are common, affecting up to a third of those who underwent bariatric surgery. Many affected individuals reported neuroglycopenic symptoms and were more likely to be female and nondiabetic and to have undergone Roux-en-Y gastric bypass. Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Influence of erythropoietin on cognitive performance during experimental hypoglycemia in patients with type 1 diabetes mellitus

DEFF Research Database (Denmark)

Kristensen, Peter Lommer; Pedersen-Bjergaard, Ulrik; Kjær, Troels Wesenberg

2013-01-01

The incidence of severe hypoglycemia in type 1 diabetes has not decreased over the past decades. New treatment modalities minimizing the risk of hypoglycemic episodes and attenuating hypoglycemic cognitive dysfunction are needed. We studied if treatment with the neuroprotective hormone...

Oral Dextrose Gel Reduces the Need for Intravenous Dextrose Therapy in Neonatal Hypoglycemia.

Science.gov (United States)

Rawat, Munmun; Chandrasekharan, Praveen; Turkovich, Stephen; Barclay, Nancy; Perry, Katherine; Schroeder, Eileen; Testa, Lisa; Lakshminrusimha, Satyan

2016-01-01

Newborn infants with risk factors may require intravenous (IV) dextrose for asymptomatic hypoglycemia. Administration of IV dextrose and transfer to the neonatal intensive care unit (NICU) may interfere with parent-infant bonding. To study the effect of implementing dextrose gel supplement with feeds in late preterm/term infants affected by asymptomatic hypoglycemia on reducing IV dextrose therapy. A retrospective study was conducted before and after dextrose gel use: 05/01/2014 to 10/31/2014 and 11/01/2014 to 04/30/2015, respectively. Asymptomatic hypoglycemic (blood glucose level dextrose gel (200 mg/kg of 40% dextrose) along with feeds. Transfer to the NICU for IV dextrose was considered treatment failure. Dextrose gel with feeds increased the blood glucose level in 184/250 (74%) of asymptomatic hypoglycemic infants compared to 144/248 (58%) with feeds only (p dextrose decreased from 35/1,000 to 25/1,000 live births (p dextrose gel with feeds reduced the need for IV fluids, avoided separation from the mother and promoted breastfeeding. Neonates who failed dextrose gel therapy were more likely to be large for gestational age, delivered by cesarean section and had lower baseline blood glucose levels.

Individuals with Type 1 and Type 2 Diabetes Mellitus Trade Increased Hyperglycemia for Decreased Hypoglycemia When Glycemic Variability is not Improved.

Science.gov (United States)

Jangam, Sujit R; Hayter, Gary; Dunn, Timothy C

2018-02-01

Glycemic variability refers to oscillations in blood glucose within a day and differences in blood glucose at the same time on different days. Glycemic variability is linked to hypoglycemia and hyperglycemia. The relationship among these three important metrics is examined here, specifically to show how reduction in both hypo- and hyperglycemia risk is dependent on changes in variability. To understand the importance of glycemic variability in the simultaneous reduction of hypoglycemia and hyperglycemia risk, we introduce the glycemic risk plot-estimated HbA1c % (eA1c) vs. minutes below 70 mg/dl (MB70) with constant variability contours for predicting post-intervention risks in the absence of a change in glycemic variability. The glycemic risk plot illustrates that individuals who do not reduce glycemic variability improve one of the two metrics (hypoglycemia risk or hyperglycemia risk) at the cost of the other. It is important to reduce variability to improve both risks. These results were confirmed by data collected in a randomized controlled trial consisting of individuals with type 1 and type 2 diabetes on insulin therapy. For type 1, a total of 28 individuals out of 35 (80%) showed improvement in at least one of the risks (hypo and/or hyper) during the 100-day course of the study. Seven individuals (20%) showed improvement in both. Similar data were observed for type 2 where a total of 36 individuals out of 43 (84%) showed improvement in at least one risk and 8 individuals (19%) showed improvement in both. All individuals in the study who showed improvement in both hypoglycemia and hyperglycemia risk also showed a reduction in variability. Therapy changes intended to improve an individual's hypoglycemia or hyperglycemia risk often result in the reduction of one risk at the expense of another. It is important to improve glucose variability to reduce both risks or at least maintain one risk while reducing the other. Abbott Diabetes Care.

Short-term cost-effectiveness of insulin detemir and insulin aspart in people with type 1 diabetes who are prone to recurrent severe hypoglycemia

DEFF Research Database (Denmark)

Pedersen-Bjergaard, Ulrik; Kristensen, Peter Lommer; Nørgaard, Kirsten

2016-01-01

to a lower event rate. QALYs were higher with insulin analogues vs. human insulin (difference 0.0672). The resulting ICER was 27,685 DKK (2674 GBP) per QALY gained, which is well below the generally accepted cost–effectiveness threshold. Conclusions: The analysis shows that treating people with type 1......Objective: Based on the data of the HypoAna trial (ClinicalTrials.gov NCT00346996), a short-term cost–effectiveness analysis was conducted comparing an all insulin analogue regimen with an all human insulin regimen in people with type 1 diabetes who are prone to recurrent severe hypoglycemia....... Methods: Clinical data from the HypoAna trial and Danish cost data related to the treatment of severe hypoglycemia were used to populate a 1-year cost–effectiveness analysis. Hypoglycemia quality-of-life data were based on previously published utility values, used to calculate the quality-adjusted life...

Pyrvinium targets the unfolded protein response to hypoglycemia and its anti-tumor activity is enhanced by combination therapy.

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De-Hua Yu

Full Text Available We identified pyrvinium pamoate, an old anthelminthic medicine, which preferentially inhibits anchorage-independent growth of cancer cells over anchorage-dependent growth (approximately 10 fold. It was also reported by others to have anti-tumor activity in vivo and selective toxicity against cancer cells under glucose starvation in vitro, but with unknown mechanism. Here, we provide evidence that pyrvinium suppresses the transcriptional activation of GRP78 and GRP94 induced by glucose deprivation or 2-deoxyglucose (2DG, a glycolysis inhibitor, but not by tunicamycin or A23187. Other UPR pathways induced by glucose starvation, e.g. XBP-1, ATF4, were also found suppressed by pyrvinium. Constitutive expression of GRP78 via transgene partially protected cells from pyrvinium induced cell death under glucose starvation, suggesting that suppression of the UPR is involved in pyrvinium mediated cytotoxicity under glucose starvation. Xenograft experiments showed rather marginal overall anti-tumor activity for pyrvinium as a monotherapy. However, the combination of pyrvinium and Doxorubicin demonstrated significantly enhanced efficacy in vivo, supporting a mechanistic treatment concept based on tumor hypoglycemia and UPR.

Preventing Unnecessary Costs of Drug-Induced Hypoglycemia in Older Adults with Type 2 Diabetes in the United States and Canada.

Science.gov (United States)

Boulin, Mathieu; Diaby, Vakaramoko; Tannenbaum, Cara

2016-01-01

The costs of drug-induced hypoglycemia are a critical but often neglected component of value-based arguments to reduce tight glycemic control in older adults with type 2 diabetes. An economic (decision-tree) analysis compared rates, costs, quality-adjusted life-years, and incremental costs per quality-adjusted life-year gained associated with mild, moderate and severe hypoglycemic events for 6 glucose-lowering medication classes in type 2 diabetic adults aged 65-79 versus those 80 years and older. The national U.S. (Center for Medicare Services) and Canadian public health payer perspectives were adopted. Incidence rates of drug-induced hypoglycemia were the highest for basal insulin and sulfonylureas: 8.64 and 4.32 events per person-year in 65-79 year olds, and 12.06 and 6.03 events per person-year for 80 years and older. In both the U.S. and Canada, metformin dominated sulfonylureas, basal insulin and glucagon-like peptide1 receptor agonists. Relative to sulfonylureas, thiazolidinediones had the lowest incremental cost-effectiveness ratios in the U.S. and dominated sulfonylureas in Canada for adults 80 years and older. Relative to sulfonylureas, dipeptidyl peptidase4 inhibitors were cost-effective for adults 80 years and older in both countries, and for 65-79 year olds in Canada. Annual costs of hypoglycemia for older adults attaining very tight glycemic control with the use of insulin or sulfonylureas were estimated at U.S.$509,214,473 in the U.S. and CAN$65,497,849 in Canada. Optimizing drug therapy for older type 2 diabetic adults through the avoidance of drug-induced hypoglycemia will dramatically improve patient health while also generating millions of dollars by saving unnecessary medical costs.

Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

International Nuclear Information System (INIS)

Wong, K.L.; Tyce, G.M.

1983-01-01

The metabolism of glucose in brains during sustained hypoglycemia was studied. [U- 14 C]Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. In the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia

NPY/AgRP neurons are not essential for feeding responses to glucoprivation.

Science.gov (United States)

Luquet, Serge; Phillips, Colin T; Palmiter, Richard D

2007-02-01

Animals respond to hypoglycemia by eating and by stimulating gluconeogenesis. These responses to glucose deprivation are initiated by glucose-sensing neurons in the brain, but the neural circuits that control feeding behavior are not well established. Neurons in the arcuate region of the hypothalamus that express neuropeptide Y (NPY) and agouti-related protein (AgRP) have been implicated in mediating the feeding response to glucoprivation. We devised a method to selectively ablate these neurons in neonatal mice and then tested adult mice for their feeding responses to fasting, mild hypoglycemia, 2-deoxy-d-glucose and a ghrelin receptor agonist. Whereas the feeding response to the ghrelin receptor agonist was completely abrogated, the feeding response to glucoprivation was normal. The feeding response after a fast was attenuated when standard chow was available but normal with more palatable solid or liquid diet. We conclude that NPY/AgRP neurons are not necessary for generating or mediating the orexigenic response to glucose deficiency, but they are essential for the feeding response to ghrelin and refeeding on standard chow after a fast.

Could Continuous Glucose Monitoring Facilitate Identifying Diabetes Patients with a Higher Risk of Hypoglycemia during Driving?

Czech Academy of Sciences Publication Activity Database

Brož, J.; Doničová, V.; Brabec, Marek; Janíčková Žďárská, D.; Polák, J.

2013-01-01

Roč. 7, č. 6 (2013), s. 1644-1645 ISSN 1932-2968 Institutional support: RVO:67985807 Keywords : continuous glucose monitoring * driving * hypoglycemia * insulin pump * prevention * type 1 diabetes mellitus Subject RIV: BB - Applied Statistics, Operational Research http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876343/

Effects of patient-reported non-severe hypoglycemia on healthcare resource use, work-time loss, and wellbeing in insulin-treated patients with diabetes in seven European countries.

Science.gov (United States)

Geelhoed-Duijvestijn, Petronella H; Pedersen-Bjergaard, Ulrik; Weitgasser, Raimund; Lahtela, Jorma; Jensen, Marie Markert; Östenson, Claes-Göran

2013-12-01

Hypoglycemia is a frequent side effect induced by insulin treatment of type 1 (T1DM) and type 2 diabetes (T2DM). Limited data exist on the associated healthcare resource use and patient impact of hypoglycemia, particularly at a country-specific level. This study investigated the effects of self-reported non-severe hypoglycemic events (NSHE) on use of healthcare resources and patient wellbeing. Patients with T1DM or insulin-treated T2DM diabetes from seven European countries were invited to complete four weekly questionnaires. Data were collected on patient demographics, NSHE occurrence in the last 7 days, hypoglycemia-related resource use, and patient impact. NSHE were defined as events with hypoglycemia symptoms, with or without blood glucose measurement, or low blood glucose measurement without symptoms, which the patient could manage without third-party assistance. Three thousand, nine hundred and fifty-nine respondents completed at least one wave of the survey, with 57% completing all four questionnaires; 3827 respondents were used for data analyses. Overall, 2.3% and 8.9% of NSHE in patients with T1DM and T2DM, respectively, resulted in healthcare professional contact. Across countries, there was a mean increase in blood glucose test use of 3.0 tests in the week following a NSHE. Among respondents who were employed (48%), loss of work-time after the last hypoglycemic event was reported for 9.7% of NSHE. Overall, 10.2% (daytime) and 8.0% (nocturnal) NSHE led to work-time loss, with a mean loss of 84.3 (daytime) and 169.6 (nocturnal) minutes among patients reporting work-time loss. Additionally, patients reported feeling tired, irritable, and having negative feelings following hypoglycemia. Direct comparisons between studies must be interpreted with caution because of different definitions of hypoglycemia severity, duration of the studies, and methods of data collection. NSHE were associated with use of extra healthcare resources and work-time loss in all

Preventing Unnecessary Costs of Drug-Induced Hypoglycemia in Older Adults with Type 2 Diabetes in the United States and Canada.

Directory of Open Access Journals (Sweden)

Mathieu Boulin

Full Text Available The costs of drug-induced hypoglycemia are a critical but often neglected component of value-based arguments to reduce tight glycemic control in older adults with type 2 diabetes.An economic (decision-tree analysis compared rates, costs, quality-adjusted life-years, and incremental costs per quality-adjusted life-year gained associated with mild, moderate and severe hypoglycemic events for 6 glucose-lowering medication classes in type 2 diabetic adults aged 65-79 versus those 80 years and older. The national U.S. (Center for Medicare Services and Canadian public health payer perspectives were adopted.Incidence rates of drug-induced hypoglycemia were the highest for basal insulin and sulfonylureas: 8.64 and 4.32 events per person-year in 65-79 year olds, and 12.06 and 6.03 events per person-year for 80 years and older. In both the U.S. and Canada, metformin dominated sulfonylureas, basal insulin and glucagon-like peptide1 receptor agonists. Relative to sulfonylureas, thiazolidinediones had the lowest incremental cost-effectiveness ratios in the U.S. and dominated sulfonylureas in Canada for adults 80 years and older. Relative to sulfonylureas, dipeptidyl peptidase4 inhibitors were cost-effective for adults 80 years and older in both countries, and for 65-79 year olds in Canada. Annual costs of hypoglycemia for older adults attaining very tight glycemic control with the use of insulin or sulfonylureas were estimated at U.S.$509,214,473 in the U.S. and CAN$65,497,849 in Canada.Optimizing drug therapy for older type 2 diabetic adults through the avoidance of drug-induced hypoglycemia will dramatically improve patient health while also generating millions of dollars by saving unnecessary medical costs.

Maintenance of high-energy brain phosphorous compounds during insulin-induced hypoglycemia in men. 31P nuclear magnetic resonance spectroscopy study

DEFF Research Database (Denmark)

Hilsted, Jannik; Jensen, K E; Thomsen, C

1988-01-01

31P nuclear magnetic resonance (NMR) spectroscopy allows noninvasive studies of cerebral energy-rich phosphorous compounds in humans. In an attempt to characterize the relationship between peripheral blood glucose concentrations and whole-brain phosphate metabolism during insulin......-induced hypoglycemia, 31P NMR spectra were obtained before and after intravenous injection of insulin (0.15 IU/kg body wt) in six men. Compared with prehypoglycemic measurements, no significant changes were found in brain content of Pi, sugar phosphates, phosphocreatine, phosphodiesters, and ATP, and brain pH remained...... constant during the experiment. These results show that the integrated brain profile of energy-rich phosphorous compounds is unaffected by experimental insulin-induced hypoglycemia in humans....

Outcome at 2 Years after Dextrose Gel Treatment for Neonatal Hypoglycemia: Follow-Up of a Randomized Trial.

Science.gov (United States)

Harris, Deborah L; Alsweiler, Jane M; Ansell, Judith M; Gamble, Gregory D; Thompson, Benjamin; Wouldes, Trecia A; Yu, Tzu-Ying; Harding, Jane E

2016-03-01

To determine neurodevelopmental outcome at 2 years' corrected age in children randomized to treatment with dextrose gel or placebo for hypoglycemia soon after birth (The Sugar Babies Study). This was a follow-up study of 184 children with hypoglycemia (dextrose (90/118, 76%) or placebo gel (94/119, 79%). Assessments were performed at Kahikatea House, Hamilton, New Zealand, and included neurologic function and general health (pediatrician assessed), cognitive, language, behavior, and motor skills (Bayley Scales of Infant and Toddler Development, Third Edition), executive function (clinical assessment and Behaviour Rating Inventory of Executive Function-Preschool Edition), and vision (clinical examination and global motion perception). Coprimary outcomes were neurosensory impairment (cognitive, language or motor score below -1 SD or cerebral palsy or blind or deaf) and processing difficulty (executive function or global motion perception worse than 1.5 SD from the mean). Statistical tests were two sided with 5% significance level. Mean (± SD) birth weight was 3093 ± 803 g and mean gestation was 37.7 ± 1.6 weeks. Sixty-six children (36%) had neurosensory impairment (1 severe, 6 moderate, 59 mild) with similar rates in both groups (dextrose 38% vs placebo 34%, relative risk 1.11, 95% CI 0.75-1.63). Processing difficulty also was similar between groups (dextrose 10% vs placebo 18%, relative risk 0.52, 95% CI 0.23-1.15). Dextrose gel is safe for the treatment of neonatal hypoglycemia, but neurosensory impairment is common among these children. Australian New Zealand Clinical Trials Registry: ACTRN 12608000623392. Copyright © 2016 Elsevier Inc. All rights reserved.

NT-pro-BNP during hypoglycemia and hypoxemia in normal subjects: impact of renin-angiotensin system activity

DEFF Research Database (Denmark)

Due-Andersen, R; Pedersen-Bjergaard, U; Høi-Hansen, T

2008-01-01

subjects with high-RAS activity and 10 subjects with low-RAS activity (age 26 +/- 1 yr; mean +/- SE) were studied in a single-blinded, randomized, counterbalanced, crossover study on three occasions separated by at least 3 wk: 1) hypoglycemia (mean nadir plasma glucose 2.7 +/- 0.5 mmol/l), 2) hypoxemia...

Maternal glycemic control and hypoglycemia in type 1 diabetic pregnancy

DEFF Research Database (Denmark)

Mathiesen, Elisabeth R; Kinsley, Brendan; Amiel, Stephanie A

2007-01-01

OBJECTIVE: To assess the safety and efficacy of insulin aspart (IAsp) versus regular human insulin (HI) in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects (n = 322) who were pregnant or planning pregnancy were randomized to IAsp...... in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes and may potentially offer some benefits in terms of postprandial glucose control and preventing severe hypoglycemia....... or HI as meal-time insulin in an open-label, parallel-group, multicenter study. Subjects had A1C pregnancy. Insulin doses were titrated toward predefined glucose targets and A1C 1C, plasma glucose...

Low-Carbohydrate Diet Impairs the Effect of Glucagon in the Treatment of Insulin-Induced Mild Hypoglycemia

DEFF Research Database (Denmark)

Ranjan, Ajenthen; Schmidt, Signe; Damm-Frydenberg, Camilla

2017-01-01

OBJECTIVE: This study compared the ability of glucagon to restore plasma glucose (PG) after mild hypoglycemia in patients with type 1 diabetes on an isocaloric high-carbohydrate diet (HCD) versus a low-carbohydrate diet (LCD). RESEARCH DESIGN AND METHODS: Ten patients with insulin pump-treated type...... 1 diabetes randomly completed 1 week of the HCD (≥250 g/day) and 1 week of the LCD (≤50 g/day). After each week, mild hypoglycemia was induced by a subcutaneous insulin bolus in the fasting state. When PG reached 3.9 mmol/L, 100 µg glucagon was given subcutaneously, followed by 500 µg glucagon 2 h...... later. RESULTS: Compared with the HCD, the LCD resulted in lower incremental rises in PG after the first (mean ± SEM: 1.3 ± 0.3 vs. 2.7 ± 0.4 mmol/L, P = 0.002) and second glucagon bolus (4.1 ± 0.2 vs. 5.6 ± 0.5 mmol/L, P = 0.002). No differences were observed between the diets regarding concentrations...

Effect of oral contraceptives and/or metformin on GLP-1 secretion and reactive hypoglycemia in PCOS

DEFF Research Database (Denmark)

Glintborg, Dorte; Mumm, Hanne; Holst, Jens Juul

2017-01-01

CONTEXT: Insulin resistance in polycystic ovary syndrome (PCOS) may increase the risk of reactive hypoglycaemia (RH) and decrease glucagon-like peptide-1 (GLP-1) secretion. The possible effects of treatment with oral contraceptives (OCP) and/or metformin on GLP-1 secretion and risk of RH in PCOS ...... significantly lower in obese vs. lean patients and were inversely associated with BMI. CONCLUSIONS: AUC GLP-1 levels were unchanged during treatment. Increased risk of hypoglycemia during metformin +OCP could be associated with increased insulin secretion.......CONTEXT: Insulin resistance in polycystic ovary syndrome (PCOS) may increase the risk of reactive hypoglycaemia (RH) and decrease glucagon-like peptide-1 (GLP-1) secretion. The possible effects of treatment with oral contraceptives (OCP) and/or metformin on GLP-1 secretion and risk of RH in PCOS......, glucose, insulin, and C-peptide during 5 h OGTT. RESULTS: Fasting GLP-1 levels increased during metformin+OCP vs. OCP treatment, whereas AUC GLP-1 levels were unchanged during medical treatment. The prevalence of reactive hypoglycemia increased from 9/65 to 14/65 after intervention (P

A single bout of high-intensity interval training reduces awareness of subsequent hypoglycemia in patients with type 1 diabetes

NARCIS (Netherlands)

Rooijackers, H.M.M.; Wiegers, E.C.; Graaf, M. van der; Thijssen, D.H.J.; Kessels, R.P.C.; Tack, C.J.J.; Galan, B.E. de

2017-01-01

High-intensity interval training (HIIT) gains increasing popularity in patients with diabetes. HIIT acutely increases plasma lactate levels. This may be important, since administration of lactate during hypoglycemia suppresses symptoms and counterregulation, whilst preserving cognitive function. We

Hypoglycemia Secondary to Sulfonylurea Ingestion in a Patient with End Stage Renal Disease: Results from a 72-Hour Fast

Directory of Open Access Journals (Sweden)

Alice Abraham

2015-01-01

Full Text Available Insulin, proinsulin, and C-peptide levels increase with sulfonylurea exposure but the acuity of increase has not been described in dialysis patients. We present a case of a dialysis patient who presented with hypoglycemia and was found to have accidental sulfonylurea ingestion. This is a 73-year-old man with ESRD on peritoneal dialysis, without history of diabetes, who presented with hypoglycemia. Past medical history includes multiple myeloma, congestive heart failure, and hypertension. At initial presentation, his blood glucose was 47 mg/dL, with concomitant elevations in the following: C-peptide 30.5 (nl: 0.8–3.5 ng/mL, insulin 76 (nl: 3–19 μIU/mL, and proinsulin 83.3 (nl: ≤8.0 pmol/L. During the 72-hour fast, which he completed without hypoglycemia, insulin declined to be within normal limits (to 12 μIU/mL; proinsulin (to 12.1 pmol/L and C-peptide (to 7.2 ng/mL levels decreased but remained elevated. The sulfonylurea screen ultimately returned positive for glipizide, clinching the diagnosis. This is the first reported case which characterizes the chronic elevation of proinsulin in a patient with ESRD, as well as its dramatic increase after a presumed solitary exposure to sulfonylurea. The 72-hour fast conducted gives insight into the clearance of insulin, proinsulin, and C-peptide after sulfonylurea ingestion in ESRD.

Diagnosis of insulinoma in a patient with hypoglycemia without obvious hyperinsulinemia.

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Coelho, Catarina; Druce, Maralyn R; Grossman, Ashley B

2009-11-01

A 41-year-old Maltese woman with a 12-month history of severe, morning episodes of confusion, blurred vision and sweating was referred to a specialist center for evaluation of fasting hypoglycemia. She was not taking medication and did not report any prior personal or familial history of endocrinopathy or other relevant pathology. Measurement of plasma glucose, insulin, C-peptide, and beta-hydroxybutyrate concentrations during a prolonged supervised fast; sulfonylurea screen; CT, MRI scan and endoscopic ultrasonography of the pancreas; calcium stimulation test; surgical exploration and intra-operative ultrasonography of the pancreas. Insulin-secreting lesion (insulinoma) in the tail of the pancreas. The tumor was resected with cure of symptoms.

Healthcare resource use, direct and indirect costs of hypoglycemia in type 1 and type 2 diabetes, and nationwide projections. Results of the HYPOS-1 study.

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Giorda, C B; Rossi, M C; Ozzello, O; Gentile, S; Aglialoro, A; Chiambretti, A; Baccetti, F; Gentile, F M; Romeo, F; Lucisano, G; Nicolucci, A

2017-03-01

To obtain an accurate picture of the total costs of hypoglycemia, including the indirect costs and comparing the differences between type 1 (T1DM) and type 2 diabetes mellitus (T2DM). HYPOS-1 was a multicenter, retrospective cohort study which analyzed the data of 2229 consecutive patients seen at 18 diabetes clinics. Data on healthcare resource use and indirect costs by diabetes type were collected via a questionnaire. The domains of inpatient admission and hospital stay, work days lost, and third-party assistance were also explored. Resource utilization was reported as estimated incidence rates (IRs) of hypoglycemic episodes per 100 person-years and estimated costs as IRs per person-years. For every 100 patients with T1DM, 9 emergency room (ER) visits and 6 emergency medical service calls for hypoglycemia were required per year; for every 100 patients with T2DM, 3 ER visits and 1 inpatient admission were required, with over 3 nights spent in hospital. Hypoglycemia led to 58 work days per 100 person-years lost by the patient or a family member in T1DM versus 19 in T2DM. The costs in T1DM totaled €90.99 per person-year and €62.04 in T2DM. Direct and indirect costs making up the total differed by type of diabetes (60% indirect costs in T1DM versus 43% in T2DM). The total cost associated with hypoglycemia in Italy is estimated to be €107 million per year. Indirect costs meaningfully contribute to the total costs associated with hypoglycemia. As compared with T1DM, T2DM requires fewer ER visits and incurs lower indirect costs but more frequent hospital use. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Effects of aging and insulin resistant states on protein anabolic responses in older adults.

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Morais, Jose A; Jacob, Kathryn Wright; Chevalier, Stéphanie

2018-07-15

Insulin is the principal postprandial anabolic hormone and resistance to its action could contribute to sarcopenia. We developed different types of hyperinsulinemic clamp protocols to measure simultaneously glucose and protein metabolism in insulin resistant states (older adults, obesity, diabetes, etc.). To define effects of healthy aging in response to insulin, we employed the hyperinsulinemic, euglycemic and isoaminoacidemic (HYPER-1) clamp. The net whole-body anabolic (protein balance) response to hyperinsulinemia was lower in the elderly vs young (p = 0.007) and was highly correlated with the clamp glucose rate of disposal (r = 0.671, p anabolism compared with young ones. As most of the anabolism occurs during feeding, we studied the fed-state metabolic responses with aging using the hyperinsulinemic, hyperglycemic and hyperaminoacidemic clamp, including muscle biopsies. Older women showed comparable whole-body protein anabolic responses and stimulation of mixed-muscle protein synthesis by feeding to the young. The responses of skeletal muscle insulin signaling through the Akt-mTORC1 pathway were also unaltered, and therefore consistent with muscle protein synthesis results. Given that type 2 diabetes infers insulin resistance of protein metabolism with aging, we studied 10 healthy, 8 obese, and 8 obese type 2 diabetic elderly women using the HYPER-1 clamp. When compared to the group of young lean women to define the effects of obesity and diabetes with aging, whole-body change in net protein balance with hyperinsulinemia was similarly blunted in obese and diabetic older women. However, only elderly obese women with diabetes had lower net balance than lean older women. We conclude that with usual aging, the blunted whole-body anabolic response in elderly subjects is mediated by the failure of insulin to stimulate protein synthesis to the same extent as in the young, especially in men. This blunted response can be overcome at the whole-body and muscle

Fear of Hypoglycemia, Parenting Stress, and Metabolic Control for Children with Type 1 Diabetes and Their Parents.

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Viaene, Ann-Sofie; Van Daele, Tom; Bleys, Dries; Faust, Kelly; Massa, Guy G

2017-03-01

This study sets out to extend current knowledge of parenting stress and fear of hypoglycemia (FoH) in parents of children with type 1 diabetes mellitus (T1DM). We examined if the relationship between parental and children's FoH and metabolic control, as reflected by HbA1c, is mediated by parenting stress. A total of 63 parents and children with T1DM were recruited during their routine physician's appointment. Parents completed questionnaires on parenting stress and FoH. Children eight years and older also completed a questionnaire on FoH. HbA1c values were obtained from all children. Mediation analysis revealed an indirect association between parental FoH and HbA1c values through parenting stress (Sobel's z = 2.42, p = .02), but no indirect association between children's FoH and HbA1c. We concluded that parental FOH has an indirect association with the child's metabolic control that is mediated by parenting stress. More simply, fear of hypoglycemia predicts parent stress, which in turn, predicts metabolic control.

Detection of hypoglycemia with continuous interstitial and traditional blood glucose monitoring using the FreeStyle Navigator Continuous Glucose Monitoring System.

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McGarraugh, Geoffrey; Bergenstal, Richard

2009-03-01

The objective of the analysis was to compare detection of hypoglycemic episodes (glucose 15 min) with the FreeStyle Navigator Continuous Glucose Monitoring System (FSN-CGM) (Abbott Diabetes Care, Alameda, CA) alarms to detection with traditional finger stick testing at an average frequency of eight tests per day. The performance of FSN-CGM alarms was evaluated in a clinic setting using 58 subjects with type 1 diabetes mellitus (T1DM) monitoring interstitial glucose concentration over a 5-day period compared to reference YSI measurements (instrument manufactured by YSI, Yellow Springs, OH) at 15-min intervals. Finger stick glucose testing was evaluated in the home environment with 91 subjects with TIDM monitoring with the blood glucose meter integrated into the FreeStyle Navigator (FSN-BG) over a 20-day period. The reference was FSN-CGM with results masked from the subjects. Blood glucose values glucose was <= 85 mg/dL 77.2% of the time. In the home environment, the average FSN-BG testing frequency was 7.9 tests per day. Hypoglycemia was verified within +/- 30 min by FSN-BG measurements <= 85 mg/dL at a rate of 27.5%. Even with a high rate of FSN-BG testing, hypoglycemia detected by FSN-CGM was verified by patients with T1DM very infrequently. A high rate of hypoglycemia detection with a moderate rate of unnecessary alarms can be attained using FSN-CGM.

Performance during a strenuous swimming session is associated with high blood lactate: pyruvate ratio and hypoglycemia in fasted rats.

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Travassos, P B; Godoy, G; De Souza, H M; Curi, R; Bazotte, R B

2018-03-26

The aim of this study was to investigate the effect of lactatemia elevation and glycemia reduction on strenuous swimming performance in fasted rats. Three rats were placed in a swimming tank at the same time. The first rat was removed immediately (control group) and the remaining ones were submitted to a strenuous swimming session. After the second rat was exhausted (Exh group), the third one was immediately removed from the water (Exe group). According to the period of time required for exhaustion, the rats were divided into four groups: low performance (3-7 min), low-intermediary performance (8-12 min), high-intermediary performance (13-17 min), and high performance (18-22 min). All rats were removed from the swimming tanks and immediately killed by decapitation for blood collection or anesthetized for liver perfusion experiments. Blood glucose, lactate, and pyruvate concentrations, blood lactate/pyruvate ratio, and liver lactate uptake and its conversion to glucose were evaluated. Exhaustion in low and low-intermediary performance were better associated with higher lactate/pyruvate ratio. On the other hand, exhaustion in high-intermediary and high performance was better associated with hypoglycemia. Lactate uptake and glucose production from lactate in livers from the Exe and Exh groups were maintained. We concluded that there is a time sequence in the participation of lactate/pyruvate ratio and hypoglycemia in performance during an acute strenuous swimming section in fasted rats. The liver had an important participation in preventing hyperlactatemia and hypoglycemia during swimming through lactate uptake and its conversion to glucose.

Polyglandular autoimmune syndrome iii with hypoglycemia and association with empty sella and hypopituitarism

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Samia Abdulla Bokhari

2017-01-01

Full Text Available A 25-year-old Saudi female with a known case of autoimmune thyroiditis presented to the Emergency Room in stuporous condition. A blood test revealed a blood sugar level of 1.7 mmols/l (30.6 mg/dl. The patient was resuscitated with intravenous glucose. Further evaluations of the patient revealed celiac disease and idiopathic thrombocytopenia with preexisting autoimmune thyroiditis (polyglandular autoimmune syndrome III [PAS III]. The severe hypoglycemia, coupled with 6 years of infertility evaluation, revealed a rare association of empty sella syndrome with hypopituitarism {PAS II}.

Position statement: hypoglycemia management in patients with diabetes mellitus. Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition.

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Mezquita-Raya, Pedro; Reyes-García, Rebeca; Moreno-Pérez, Óscar; Muñoz-Torres, Manuel; Merino-Torres, Juan Francisco; Gorgojo-Martínez, Juan José; Jódar-Gimeno, Esteban; Escalada San Martín, Javier; Gargallo-Fernández, Manuel; Soto-Gonzalez, Alfonso; González Pérez de Villar, Noemí; Becerra Fernández, Antonio; Bellido Guerrero, Diego; Botella-Serrano, Marta; Gómez-Peralta, Fernando; López de la Torre Casares, Martín

2013-11-01

To provide practical recommendations for evaluation and management of hypoglycemia in patients with diabetes mellitus. Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition. Recommendations were formulated according to the Grading of Recommendations, Assessment, Development, and Evaluation system to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (PubMed). Papers in English and Spanish with publication date before 15 February 2013 were included. For recommendations about drugs only those approved by the European Medicines Agency were included. After formulation of recommendations, they were discussed by the Working Group. The document provides evidence-based practical recommendations for evaluation and management of hypoglycemia in patients with diabetes mellitus. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia

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Hering, Bernhard J.; Clarke, William R.; Bridges, Nancy D.; Eggerman, Thomas L.; Alejandro, Rodolfo; Bellin, Melena D.; Chaloner, Kathryn; Czarniecki, Christine W.; Goldstein, Julia S.; Hunsicker, Lawrence G.; Kaufman, Dixon B.; Korsgren, Olle; Larsen, Christian P.; Luo, Xunrong; Markmann, James F.; Naji, Ali; Oberholzer, Jose; Posselt, Andrew M.; Rickels, Michael R.; Ricordi, Camillo; Robien, Mark A.; Senior, Peter A.; Shapiro, A.M. James; Stock, Peter G.; Turgeon, Nicole A.

2016-01-01

OBJECTIVE Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50–80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. RESEARCH DESIGN AND METHODS This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA1c transplant. RESULTS The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA1c level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients. CONCLUSIONS Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding

Triglyceride glucose index as a surrogate measure of insulin sensitivity in obese adolescents with normoglycemia, prediabetes, and type 2 diabetes mellitus: comparison with the hyperinsulinemic-euglycemic clamp.

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Mohd Nor, Noor Shafina; Lee, SoJung; Bacha, Fida; Tfayli, Hala; Arslanian, Silva

2016-09-01

There is a need for simple surrogate estimates of insulin sensitivity in epidemiological studies of obese youth because the hyperinsulinemic-euglycemic clamp is not feasible on a large scale. (i) To examine the triglyceride glucose (TyG) index (Ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]) and its relationship to in vivo insulin sensitivity in obese adolescents (OB) along the spectrum of glucose tolerance and (ii) to compare TyG index with triglyceride/high-density lipoprotein TG/HDL and 1/fasting insulin (1/IF ), other surrogates of insulin sensitivity. Cross-sectional data in 225 OB with normal glucose tolerance (NGT), prediabetes (preDM), and type 2 diabetes (T2DM) who had a 3-h hyperinsulinemic-euglycemic clamp and fasting lipid measurement. Insulin-stimulated glucose disposal (Rd) declined significantly across the glycemic groups from OB-NGT to OB-preDM to OB-T2DM with a corresponding increase in TyG index (8.3 ± 0.5, 8.6 ± 0.5, 8.9 ± 0.6, p index to Rd was -0.419 (p index for diagnosis of insulin resistance was 8.52 [receiver operating characteristic-area under the ROC curves (ROC-AUC) 0.750, p index, 1/IF , body mass index (BMI) z-score, glycemic group, and sex. The TyG index affords an easily and widely available simple laboratory method as a surrogate estimate of insulin sensitivity that could be used repeatedly in large-scale observational and/or interventional cohorts of OB. Although not superior to 1/IF , TyG index offers the advantage of having a standardized method of measuring triglyceride and glucose, which is not the case for insulin assays. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Delineation of glutamate pathways and secretory responses in pancreatic islets with ß-cell-specific abrogation of the glutamate dehydrogenase

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Vetterli, Laurene; Carobbio, Stefania; Pournourmohammadi, Shirin

2012-01-01

isolated from βGlud1(-/-) mice exhibited half of the response measured in control islets. The amplifying pathway, tested at stimulatory glucose concentrations in the presence of KCl and diazoxide, was markedly inhibited in βGlud1(-/-) islets. On glucose stimulation, net synthesis of glutamate from α......-ketoglutarate was impaired in GDH-deficient islets. Accordingly, glucose-induced elevation of glutamate levels observed in control islets was absent in βGlud1(-/-) islets. Parallel biochemical pathways, namely alanine and aspartate aminotransferases, could not compensate for the lack of GDH. However, the secretory response...... to glucose was fully restored by the provision of cellular glutamate when βGlud1(-/-) islets were exposed to dimethyl glutamate. This shows that permissive levels of glutamate are required for the full development of glucose-stimulated insulin secretion and that GDH plays an indispensable role...

Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

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Højlund, Kurt

2014-01-01

. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance....... Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin...

Residual β-Cell Function 3 to 6 Years After Onset of Type 1 Diabetes Reduces Risk of Severe Hypoglycemia in Children and Adolescents

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Sorensen, Jesper Sand; Johannesen, Jesper; Pociot, Flemming

2013-01-01

OBJECTIVETo determine the prevalence of residual -cell function (RBF) in children after 3-6 years of type 1 diabetes, and to examine the association between RBF and incidence of severe hypoglycemia, glycemic control, and insulin requirements.RESEARCH DESIGN AND METHODSA total of 342 children (173....../mol]; P 0.2 nmol/L (mean +/- SE: 1.07 +/- 0.02 vs. 0.93 +/- 0.07 units/kg/day; P children after 3-6 years of type 1 diabetes. Children with RBF...... boys) 4.8-18.9 years of age with type 1 diabetes for 3-6 years were included. RBF was assessed by testing meal-stimulated C-peptide concentrations. Information regarding severe hypoglycemia within the past year, current HbA(1c), and daily insulin requirements was retrieved from the medical records...

The Role of Interleukin-6 in Lipopolysaccharide-Induced Weight Loss, Hypoglycemia and Fibrinogen Production, in Vivo

Science.gov (United States)

1994-07-01

result in chronic wasting or cachexia. In neoplastic severe weight loss in syngeneic hosts.6 In this model, diseases, the presence of wasting of muscle...48 h post-endotoxin). Anti-TNF MAb tribution of TNF and IL-6 in several metabolic changes reduced by c. 50% the LPS-induced weight loss, but...similar results. Also, the addi- hypertriglyceridemia , hypoglycemia as well as stimu- tion of fresh 20F3 MAb to diluted serum sample from late the

Mitochondria from rat uterine smooth muscle possess ATP-sensitive potassium channel

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Olga B. Vadzyuk

2018-03-01

Full Text Available The objective of this study was to detect ATP-sensitive K+ uptake in rat uterine smooth muscle mitochondria and to determine possible effects of its activation on mitochondrial physiology. By means of fluorescent technique with usage of K+-sensitive fluorescent probe PBFI (potassium-binding benzofuran isophthalate we showed that accumulation of K ions in isolated mitochondria from rat myometrium is sensitive to effectors of KATP-channel (ATP-sensitive K+-channel – ATP, diazoxide, glibenclamide and 5HD (5-hydroxydecanoate. Our data demonstrates that K+ uptake in isolated myometrium mitochondria results in a slight decrease in membrane potential, enhancement of generation of ROS (reactive oxygen species and mitochondrial swelling. Particularly, the addition of ATP into incubation medium led to a decrease in mitochondrial swelling and ROS production, and an increase in membrane potential. These effects were eliminated by diazoxide. If blockers of KATP-channel were added along with diazoxide, the effects of diazoxide were removed. So, we postulate the existence of KATP-channels in rat uterus mitochondria and assume that their functioning may regulate physiological conditions of mitochondria, such as matrix volume, ROS generation and polarization of mitochondrial membrane. Keywords: ATP-sensitive potassium channel, Diazoxide, 5-hydroxydecanoate, Myometrium, Mitochondria, Mitochondrial swelling, Mitochondrial membrane potential, ROS

Elevation of serum insulin concentration during euglycemic hyperinsulinemic clamp studies leads to similar activation of insulin receptor kinase in skeletal muscle of subjects with and without NIDDM

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Klein, H H; Vestergaard, H; Kotzke, G

1995-01-01

The role of skeletal muscle insulin receptor kinase in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) was investigated. Muscle biopsies from 13 patients with NIDDM and 10 control subjects at fasting serum insulin concentrations and approximately 1,000 pmol/l steady-state serum...... insulin during euglycemic hyperinsulinemic clamps were immediately frozen. The biopsies were then solubilized, and the receptors were immobilized to anti-insulin receptor antibody-coated microwells. Receptor kinase and binding activities were consecutively measured in these wells. The increase in serum...... and control groups, respectively). Moreover, by selecting only the receptors that bound to anti-phosphotyrosine antibody, we found similar hyperinsulinemia-induced increases of this receptor fraction and its kinase activity in both study groups. In vitro activation of the immobilized receptors with 2 mmol...

Numerical and clinical precision of continuous glucose monitoring in Colombian patients treated with insulin infusion pump with automated suspension in hypoglycemia.

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Gómez, Ana M; Marín Sánchez, Alejandro; Muñoz, Oscar M; Colón Peña, Christian Alejandro

2015-12-01

Insulin pump therapy associated with continuous glucose monitoring has shown a positive clinical impact on diabetes control and reduction of hypoglycemia episodes. There are descriptions of the performance of this device in other populations, but its precision and accuracy in Colombia and Latin America are unknown, especially in the routine outpatient setting. Data from 33 type 1 and type 2 diabetes patients with sensor-augmented pump therapy with threshold suspend automation, MiniMed Paradigm® Veo™ (Medtronic, Northridge, California), managed at Hospital Universitario San Ignacio (Bogotá, Colombia) and receiving outpatient treatment, were analyzed. Simultaneous data from continuous glucose monitoring and capillary blood glucose were compared, and their precision and accuracy were calculating with different methods, including Clarke error grid. Analyses included 2,262 continuous glucose monitoring -reference paired glucose values. A mean absolute relative difference of 20.1% was found for all measurements, with a value higher than 23% for glucose levels ≤75mg/dL. Global compliance with the ISO criteria was 64.9%. It was higher for values >75mg/dl (68.3%, 1,308 of 1,916 readings), than for those ≤ 75mg/dl (49.4%, 171 of 346 readings). Clinical accuracy, as assessed by the Clarke error grid, showed that 91.77% of data were within the A and B zones (75.6% in hypoglycemia). A good numerical accuracy was found for continuous glucose monitoring in normo and hyperglycemia situations, with low precision in hypoglycemia. The clinical accuracy of the device was adequate, with no significant safety concerns for patients. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Nationwide reduction in the frequency of severe hypoglycemia by half

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Fredheim, S.; Johansen, A.; Thorsen, S. U.

2015-01-01

Aims: To examine contemporary rates of severe hypoglycemia (SH) and identify the effect of predictors of SH in a pediatric type 1 diabetes population. Methods: The national diabetes register provided data on children residing in Denmark from 2008 to 2013 in this register-based population study....... Robust Poisson regression models were applied. Results: The study population [n = 2,715 (50.9 % boys), mean (SD) age at onset; 8.1 (4.0) years, diabetes duration; 5.6 (4.9) years] comprised 7,390 person-years of data and 561 events of SH. The overall incidence of SH was 7.6 per 100 person......-years. The incidence rate peaked with 16.0 per 100 person-years in 2008 reaching a nadir of 4.9 in 2011. Overall, insulin pump reduced the rate of SH with 27 % compared to any pen treatment (P = 0.003). When stratifying pen treatment, premixed insulin increased the rate of SH by 1.9-fold (P = 0.0015) and NPH increased...

Arrhythmogenic effects of hypoglycemia in children and adolescents with type 1 diabetes mellitus

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Dmitriy Nikitich Laptev

2013-12-01

Full Text Available Aim. To determine the effects of hypoglycemia on the duration of QT interval, heart rate variability (HRV and frequency of arrhythmic events, as well as to closer investigate the factors associated with the development of various heart rhythm disorders in children and adolescents with type 1 diabetes mellitus (T1DM. Materials and methods.  The study included 150 children and adolescents with T1DM at the age of 6?18 years. All participants underwent Holter monitoring and continuous glucose monitoring (CGM for 24 hours. QTc and HRV parameters (SDNN, RMSSD, SVVR were calculated automatically. Data was averaged for 5?-interval and juxtaposed with CGM. Patients identified with hypoglycemic events (blood glucose

Screening for hypoglycemia at the bedside in the neonatal intensive care unit (NICU with the Abbott PCx glucose meter

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Ismaila Afisi

2006-11-01

Full Text Available Abstract Background Point of care (POC glucose meters are routinely used as a screening tool for hypoglycemia in a neonatal setting. Glucose meters however, lack the same accuracy as laboratory instruments for glucose measurement. In this study we investigated potential reasons for this inaccuracy and established a cut off value for confirmatory testing. Methods In this prospective study, all patients in the neonatal intensive care unit who had a plasma glucose test ordered were eligible to participate. Demographic information, sample collection information (nine variables and a recent hematocrit value were recorded for each sample. Glucose measurements were taken at the bedside on the glucose meter (RN PCx as well as in the laboratory on both the glucose meter (LAB PCx and the laboratory analyzer (PG. Data were analyzed by simple and mixed-effects regression analysis and by analysis of a receiver operator characteristics (ROC curve. Results There were 475 samples analyzed from 132 patients. RN PCx values were higher than PG values (mean = 4.9%, while LAB PCx results were lower (mean = -5.2% than PG values. Only 31% of the difference between RN PCx – PG and 46% of the difference for LAB PCx – PG could be accounted for by the variables tested. The largest proportion of variance between PCx and PG measurements was explained by hematocrit (about 30% with a greater effect seen at glucose concentrations ≤4.0 mmol/L (≤72 mg/dL(48% and 40% for RN PCx and LAB PCx, respectively. The ROC analysis showed that for detection of all cases of hypoglycemia (PG Conclusion The large difference between glucose results obtained by PCx glucose meter compared to the laboratory analyzer can be explained in part by hematocrit and low glucose concentration. These results emphasize that the glucose meter is useful only as a screening device for neonatal hypoglycemia and that a screening cut off value must be established.

Screening for hypoglycemia at the bedside in the neonatal intensive care unit (NICU) with the Abbott PCx glucose meter.

Science.gov (United States)

Balion, Cynthia; Grey, Vijaylaxmi; Ismaila, Afisi; Blatz, Susan; Seidlitz, Wendy

2006-11-03

Point of care (POC) glucose meters are routinely used as a screening tool for hypoglycemia in a neonatal setting. Glucose meters however, lack the same accuracy as laboratory instruments for glucose measurement. In this study we investigated potential reasons for this inaccuracy and established a cut off value for confirmatory testing. In this prospective study, all patients in the neonatal intensive care unit who had a plasma glucose test ordered were eligible to participate. Demographic information, sample collection information (nine variables) and a recent hematocrit value were recorded for each sample. Glucose measurements were taken at the bedside on the glucose meter (RN PCx) as well as in the laboratory on both the glucose meter (LAB PCx) and the laboratory analyzer (PG). Data were analyzed by simple and mixed-effects regression analysis and by analysis of a receiver operator characteristics (ROC) curve. There were 475 samples analyzed from 132 patients. RN PCx values were higher than PG values (mean = 4.9%), while LAB PCx results were lower (mean = -5.2%) than PG values. Only 31% of the difference between RN PCx--PG and 46% of the difference for LAB PCx--PG could be accounted for by the variables tested. The largest proportion of variance between PCx and PG measurements was explained by hematocrit (about 30%) with a greater effect seen at glucose concentrations LAB PCx, respectively). The ROC analysis showed that for detection of all cases of hypoglycemia (PG < 2.6 mmol/L)(PG < 47 mg/dL) the PCx screening cut off value would need to be set at 3.8 mmol/L (68 mg/dL) requiring 20% of all samples to have confirmatory analysis by the laboratory method. The large difference between glucose results obtained by PCx glucose meter compared to the laboratory analyzer can be explained in part by hematocrit and low glucose concentration. These results emphasize that the glucose meter is useful only as a screening device for neonatal hypoglycemia and that a screening

Validation of different measures of insulin sensitivity of glucose metabolism in dairy cows using the hyperinsulinemic euglycemic clamp test as the gold standard.

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De Koster, J; Hostens, M; Hermans, K; Van den Broeck, W; Opsomer, G

2016-10-01

The aim of the present research was to compare different measures of insulin sensitivity in dairy cows at the end of the dry period. To do so, 10 clinically healthy dairy cows with a varying body condition score were selected. By performing hyperinsulinemic euglycemic clamp (HEC) tests, we previously demonstrated a negative association between the insulin sensitivity and insulin responsiveness of glucose metabolism and the body condition score of these animals. In the same animals, other measures of insulin sensitivity were determined and the correlation with the HEC test, which is considered as the gold standard, was calculated. Measures derived from the intravenous glucose tolerance test (IVGTT) are based on the disappearance of glucose after an intravenous glucose bolus. Glucose concentrations during the IVGTT were used to calculate the area under the curve of glucose and the clearance rate of glucose. In addition, glucose and insulin data from the IVGTT were fitted in the minimal model to derive the insulin sensitivity parameter, Si. Based on blood samples taken before the start of the IVGTT, basal concentrations of glucose, insulin, NEFA, and β-hydroxybutyrate were determined and used to calculate surrogate indices for insulin sensitivity, such as the homeostasis model of insulin resistance, the quantitative insulin sensitivity check index, the revised quantitative insulin sensitivity check index and the revised quantitative insulin sensitivity check index including β-hydroxybutyrate. Correlation analysis revealed no association between the results obtained by the HEC test and any of the surrogate indices for insulin sensitivity. For the measures derived from the IVGTT, the area under the curve for the first 60 min of the test and the Si derived from the minimal model demonstrated good correlation with the gold standard. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypoglycemia in type 1 diabetic pregnancy: role of preconception insulin aspart treatment in a randomized study

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Heller, Simon; Damm, Peter; Mersebach, Henriette

2010-01-01

OBJECTIVE A recent randomized trial compared prandial insulin aspart (IAsp) with human insulin in type 1 diabetic pregnancy. The aim of this exploratory analysis was to investigate the incidence of severe hypoglycemia during pregnancy and compare women enrolled preconception with women enrolled...... during early pregnancy. RESEARCH DESIGN AND METHODS IAsp administered immediately before each meal was compared with human insulin administered 30 min before each meal in 99 subjects (44 to IAsp and 55 to human insulin) randomly assigned preconception and in 223 subjects (113 for IAsp and 110 for human...

Effects of Preceding Ethanol Intake on Glucose Response to Low-Dose Glucagon in Individuals With Type 1 Diabetes

DEFF Research Database (Denmark)

Ranjan, Ajenthen; Nørgaard, Kirsten; Tetzschner, Rikke

2018-01-01

OBJECTIVE: This study investigated whether preceding ethanol intake impairs glucose response to low-dose glucagon in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a randomized, crossover, placebo-controlled study in 12 insulin pump-treated individuals (median...... ethanol compared with placebo. The second glucagon bolus had similar responses between visits, but PG remained 1.8 ± 0.7 mmol/L lower after ethanol compared with placebo. CONCLUSIONS: The ability of low-dose glucagon to treat mild hypoglycemia persisted with preceding ethanol intake, although it tended...... to be metabolized, and a subcutaneous (s.c.) insulin bolus was given to induce mild hypoglycemia. When plasma glucose (PG) was ≤3.9 mmol/L, 100 µg glucagon was given s.c., followed by another s.c. 100 µg glucagon 2 h later. Primary end point was incremental peak PG induced by the first glucagon bolus. RESULTS...

Non-invasive biosensor and wilreless interrogating system for hypoglycemia

Science.gov (United States)

Varadan, Vijay K.; Whitchurch, Ashwin K.; Saukesi, K.

2002-11-01

Hypoglycemia - abnormal decrease in blood sugar - is a major obstacle in the management of diabetes and prevention of long-term complications, and it may impose serious effects on the brain, including impairment of memory and other cognitive functions. This paper presents the development of a non-invasive sensor with miniaturized telemetry device in a wrist-watch for monitoring glucose concentration in blood. The sensor concept is based on optical chiralit of glucose level in the interstitial fluid. The wrist watch consists of a laser power source of the wavelength compatible with the glucose. A nanofilm with specific chirality is placed at the bottom of the watch. The light then passes through the film and illuminates a small area on the skin.It has been documented that there is certain concentration of sugar level is taken by the intertitial fluid from the blood stream and deposit a portion of it at the dead skin. The wrist-watch when in contact with the outer skin of the human will thus monitor the glucose concentration. A wireless monitoring system in the watch then downloads the data from the watch to a Palm or laptop computer.

Association of Insulin Pump Therapy vs Insulin Injection Therapy With Severe Hypoglycemia, Ketoacidosis, and Glycemic Control Among Children, Adolescents, and Young Adults With Type 1 Diabetes.

Science.gov (United States)

Karges, Beate; Schwandt, Anke; Heidtmann, Bettina; Kordonouri, Olga; Binder, Elisabeth; Schierloh, Ulrike; Boettcher, Claudia; Kapellen, Thomas; Rosenbauer, Joachim; Holl, Reinhard W

2017-10-10

Insulin pump therapy may improve metabolic control in young patients with type 1 diabetes, but the association with short-term diabetes complications is unclear. To determine whether rates of severe hypoglycemia and diabetic ketoacidosis are lower with insulin pump therapy compared with insulin injection therapy in children, adolescents, and young adults with type 1 diabetes. Population-based cohort study conducted between January 2011 and December 2015 in 446 diabetes centers participating in the Diabetes Prospective Follow-up Initiative in Germany, Austria, and Luxembourg. Patients with type 1 diabetes younger than 20 years and diabetes duration of more than 1 year were identified. Propensity score matching and inverse probability of treatment weighting analyses with age, sex, diabetes duration, migration background (defined as place of birth outside of Germany or Austria), body mass index, and glycated hemoglobin as covariates were used to account for relevant confounders. Type 1 diabetes treated with insulin pump therapy or with multiple (≥4) daily insulin injections. Primary outcomes were rates of severe hypoglycemia and diabetic ketoacidosis during the most recent treatment year. Secondary outcomes included glycated hemoglobin levels, insulin dose, and body mass index. Of 30 579 patients (mean age, 14.1 years [SD, 4.0]; 53% male), 14 119 used pump therapy (median duration, 3.7 years) and 16 460 used insulin injections (median duration, 3.6 years). Patients using pump therapy (n = 9814) were matched with 9814 patients using injection therapy. Pump therapy, compared with injection therapy, was associated with lower rates of severe hypoglycemia (9.55 vs 13.97 per 100 patient-years; difference, -4.42 [95% CI, -6.15 to -2.69]; P young patients with type 1 diabetes, insulin pump therapy, compared with insulin injection therapy, was associated with lower risks of severe hypoglycemia and diabetic ketoacidosis and with better glycemic control during the

Severe Unresponsive Hypoglycemia Associated with Neuroendocrine Tumor of Unknown Primary Site - 18 Years after Rectal Cancer Surgery. Case Report.

Science.gov (United States)

Rusu, Octavia Cristina; Costea, Radu Virgil; Popa, Cristian Constantin; Iliesiu, Andreea; Dumitru, Adrian; Becheanu, Gabriel; Neagu, Stefan Ilie

2015-09-01

Neuroendocrine tumors are derived from cells that have the unique ability to synthesize, store and secrete a variety of metabolically active substances, peptides and amines, characteristic of the tissue of origin, which can cause distinct clinical syndromes. We present the case of a 58-year-old patient diagnosed and surgically treated in January 1996 for stage III inferior rectal cancer, who was readmitted after 18 years presenting persistent diarrheic syndrome and asthenia. Investigations performed (abdominal CT) showed multiple liver metastases, initially suspected as being related to the rectal cancer. Biopsy of liver metastases and pathological and immunohistochemical analysis demonstrated the neuroendocrine origin (moderately differentiated neuroendocrine tumor). Seven months after the identification of liver metastases and after initiation of oncological therapy with Interferon and Somatostatin, the patient presented severe hypoglycemia (serum glucose 13-70 mg/dl) proved to be due to insulin-like factors (serum insulin level 64.9 ìU/ml) secreted by metastases. Due to the aggressive evolution of neuroendocrine tumor, with multiple episodes of severe hypoglycemia, resistant to treatment, the patient died approximately one month after the occurrence of hypoglycemic episodes. Despite comprehensive tests (abdominal CT scan, colonoscopy, bone scintigraphy and PET/CT), the primary site of the neuroendocrine tumors remained unknown.

Altered glucose metabolism after bariatric surgery: What's GLP-1 got to do with it?

Science.gov (United States)

Smith, Eric P; Polanco, Georgina; Yaqub, Abid; Salehi, Marzieh

2018-06-01

Bariatric surgery is an effective treatment for obesity. The two widely performed weight-loss procedures, Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG), alter postprandial glucose pattern and enhance gut hormone secretion immediately after surgery before significant weight loss. This weight-loss independent glycemic effects of GB has been attributed to an accelerated nutrient transit from stomach pouch to the gut and enhanced secretion of insulinotropic gut factors; in particular, glucagon-like peptide-1 (GLP-1). Meal-induced GLP-1 secretion is as much as tenfold higher in patients after GB compared to non-surgical individuals and inhibition of GLP-1 action during meals reduces postprandial hyperinsulinemia after GB two to three times more than that in persons without surgery. Moreover, in a subgroup of patients with the late complication of postprandial hyperinsulinemic hypoglycemia after GB, GLP1R blockade reverses hypoglycemia by reducing meal stimulated insulin secretion. The role of enteroinsular axis activity after SG, an increasingly popular alternative to GB, is less understood but, similar to GB, SG accelerates nutrient delivery to the intestine, improves glucose tolerance, and increases postprandial GLP-1 secretion. This review will focus on the current evidence for and against the role of GLP-1 on glycemic effects of GB and will also highlight differences between GB and SG. Copyright © 2017 Elsevier Inc. All rights reserved.

Diabetes management and hypoglycemia in safety sensitive jobs.

Science.gov (United States)

Lee, See-Muah; Koh, David; Chui, Winnie Kl; Sum, Chee-Fang

2011-03-01

The majority of people diagnosed with diabetes mellitus are in the working age group in developing countries. The interrelationship of diabetes and work, that is, diabetes affecting work and work affecting diabetes, becomes an important issue for these people. Therapeutic options for the diabetic worker have been developed, and currently include various insulins, insulin sensitizers and secretagogues, incretin mimetics and enhancers, and alpha glucosidase inhibitors. Hypoglycemia and hypoglycaemic unawareness are important and unwanted treatment side effects. The risk they pose with respect to cognitive impairment can have safety implications. The understanding of the therapeutic options in the management of diabetic workers, blood glucose awareness training, and self-monitoring blood glucose will help to mitigate this risk. Employment decisions must also take into account the extent to which the jobs performed by the worker are safety sensitive. A risk assessment matrix, based on the extent to which a job is considered safety sensitive and based on the severity of the hypoglycaemia, may assist in determining one's fitness to work. Support at the workplace, such as a provision of healthy food options and arrangements for affected workers will be helpful for such workers. Arrangements include permission to carry and consume emergency sugar, flexible meal times, self-monitoring blood glucose when required, storage/disposal facilities for medicine such as insulin and needles, time off for medical appointments, and structured self-help programs.

GLP1 and glucagon co-secreting pancreatic neuroendocrine tumor presenting as hypoglycemia after gastric bypass

DEFF Research Database (Denmark)

Guimarães, Marta; Rodrigues, Pedro; Pereira, Sofia S

2015-01-01

for the treatment of severe obesity, a 54-year-old female with previous type 2 diabetes, developed post-prandial sweating, fainting and hypoglycemic episodes, which eventually led to the finding by ultrasound of a 1.8-cm solid mass in the pancreatic head. The 72-h fast test and the plasma chromogranin A levels were...... (471 pmol/g), insulin (139 pmol/g) and somatostatin (23 pmol/g). This is the first report of a GLP1 and glucagon co-secreting pNET presenting as hypoglycemia after gastric bypass surgery. Although pNET are rare, they should be considered in the differential diagnosis of the clinical approach...

Outcome at two years after dextrose gel treatment for neonatal hypoglycemia; Follow up of a randomized trial

Science.gov (United States)

Harris, Deborah L; Alsweiler, Jane M; Ansell, Judith M; Gamble, Greg D; Thompson, Ben; Wouldes, Trecia A; Yu, Tzu-Ying; Harding, Jane E

2015-01-01

Objective To determine neurodevelopmental outcome at two years’ corrected age in children randomized to treatment with dextrose gel or placebo for hypoglycemia soon after birth (The Sugar Babies Study). Study design This was a follow-up study of 184 children who had been hypoglycemic (dextrose (90/118, 76%) or placebo gel (94/119, 79%). Assessments were performed at Kahikatea House, Hamilton, New Zealand, and included neurological function and general health (Pediatrician assessed), cognitive, language, behaviour and motor skills (Bayley-III), executive function (clinical assessment and BRIEF-P), and vision (clinical examination and global motion perception). Co-primary outcomes were neurosensory impairment (cognitive, language or motor score below −1 SD or cerebral palsy or blind or deaf) and processing difficulty (executive function or global motion perception worse than 1.5 SD from the mean). Statistical tests were two sided with 5% significance level. Results Mean (±SD) birth weight was 3093 ± 803 g and mean gestation was 37.7 ±1.6 weeks. Sixty-six children (36%) had neurosensory impairment (1 severe, 6 moderate, 59 mild) with similar rates in both groups (dextrose 38% vs. placebo 34%, RR 1.11, 95% CI 0.75–1.63). Processing difficulty was also similar between groups (dextrose 10% vs. placebo 18%, RR 0.52, 95% CI 0.23–1.15). Conclusions Dextrose gel is safe for treatment of neonatal hypoglycemia, but neurosensory impairment is common amongst these children. PMID:26613985

Hypoglycemia in type 1 diabetic pregnancy: role of preconception insulin aspart treatment in a randomized study

DEFF Research Database (Denmark)

Heller, Simon; Damm, Peter; Mersebach, Henriette

2010-01-01

OBJECTIVE A recent randomized trial compared prandial insulin aspart (IAsp) with human insulin in type 1 diabetic pregnancy. The aim of this exploratory analysis was to investigate the incidence of severe hypoglycemia during pregnancy and compare women enrolled preconception with women enrolled...... during early pregnancy. RESEARCH DESIGN AND METHODS IAsp administered immediately before each meal was compared with human insulin administered 30 min before each meal in 99 subjects (44 to IAsp and 55 to human insulin) randomly assigned preconception and in 223 subjects (113 for IAsp and 110 for human...... insulin) randomly assigned in early pregnancy (...

Metastatic extrapleural malignant solitary fibrous tumor presenting with hypoglycemia (Doege–Potter syndrome

Directory of Open Access Journals (Sweden)

Andrew J. Degnan, MD, MPhil

2017-03-01

Full Text Available We report a rare case of metastatic malignant solitary fibrous tumor (SFT that presented with hypoglycemia because of insulin growth factor-2 production. Initial workup included computed tomography imaging that revealed a large, partially necrotic liver mass, a hypervascular pancreatic head lesion, and 2 renal lesions. Following hepatic resection, pancreatic head resection and nephrectomy, all these lesions demonstrated pathological findings that were consistent with SFT. The patient also had a history of an intracranial mass that had been previously resected and treated with gamma knife therapy at an outside institution, which was found to also be SFT. Six months after initial pancreatic head resection, the patient developed a new lesion involving the pancreatic tail that was found to represent recurrent metastatic SFT. This case emphasizes the highly aggressive nature of extrapleural SFT, while rare, and the role of imaging in follow-up for disease recurrence.

Screening for hypoglycemia at the bedside in the neonatal intensive care unit (NICU) with the Abbott PCx glucose meter

OpenAIRE

Balion, Cynthia; Grey, Vijaylaxmi; Ismaila, Afisi; Blatz, Susan; Seidlitz, Wendy

2006-01-01

Abstract Background Point of care (POC) glucose meters are routinely used as a screening tool for hypoglycemia in a neonatal setting. Glucose meters however, lack the same accuracy as laboratory instruments for glucose measurement. In this study we investigated potential reasons for this inaccuracy and established a cut off value for confirmatory testing. Methods In this prospective study, all patients in the neonatal intensive care unit who had a plasma glucose test ordered were eligible to ...

A prospective study of severe hypoglycemia and long-term spatial memory in children with type 1 diabetes.

Science.gov (United States)

Hershey, Tamara; Lillie, Rema; Sadler, Michelle; White, Neil H

2004-06-01

In a previous retrospective study, severe hypoglycemia (SH) was associated with decreased long-term spatial memory in children with type 1 diabetes mellitus (T1DM). In this study, we tested the hypothesis that prospectively ascertained SH would also be associated with decreased spatial long-term memory over time. Children with T1DM (n = 42) and sibling controls (n = 25) performed a spatial delayed response (SDR) task with short and long delays and other neuropsychological tests at baseline and after 15 months of monitoring. Extreme glycemic events and other medical complications were recorded prospectively during follow-up. Fourteen T1DM children experienced at least one episode of SH during the follow-up period (range = 1-5). After controlling for long-delay SDR performance at baseline, age, gender, and age of onset, the presence of SH during the prospective period was statistically associated with decreased long-delay SDR performance at follow-up (semipartial r = -0.38, p = 0.017). This relationship was not seen with short-delay SDR or with verbal or object memory, attention, or motor speed. These results, together with previously reported data, support the hypothesis that SH has specific, negative effects on spatial memory skills in T1DM children.

Diabetes Management and Hypoglycemia in Safety Sensitive Jobs

Directory of Open Access Journals (Sweden)

See-Muah Lee

2011-03-01

Full Text Available The majority of people diagnosed with diabetes mellitus are in the working age group in developing countries. The interrelationship of diabetes and work, that is, diabetes affecting work and work affecting diabetes, becomes an important issue for these people. Therapeutic options for the diabetic worker have been developed, and currently include various insulins, insulin sensitizers and secretagogues, incretin mimetics and enhancers, and alpha glucosidase inhibitors. Hypoglycemia and hypoglycaemic unawareness are important and unwanted treatment side effects. The risk they pose with respect to cognitive impairment can have safety implications. The understanding of the therapeutic options in the management of diabetic workers, blood glucose awareness training, and self-monitoring blood glucose will help to mitigate this risk. Employment decisions must also take into account the extent to which the jobs performed by the worker are safety sensitive. A risk assessment matrix, based on the extent to which a job is considered safety sensitive and based on the severity of the hypoglycaemia, may assist in determining one's fitness to work. Support at the workplace, such as a provision of healthy food options and arrangements for affected workers will be helpful for such workers. Arrangements include permission to carry and consume emergency sugar, flexible meal times, self-monitoring blood glucose when required, storage/disposal facilities for medicine such as insulin and needles, time off for medical appointments, and structured self-help rogams.

Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds.

Science.gov (United States)

Yoshida, Ryusuke; Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F; Ninomiya, Yuzo

2015-11-01

Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor-deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

A cross-sectional survey among patients and prescribers on insulin dosing irregularities and impact of mild (self-treated) hypoglycemia episodes in Spanish patients with type 2 diabetes as compared to other European patients.

Science.gov (United States)

Ampudia-Blasco, Francisco J; Galán, Manuel; Brod, Meryl

2014-10-01

In Spain, data suggest that 13.8% of adults have diabetes. Two important aspects in diabetes management are mild hypoglycemic episodes and poor treatment adherence. This study assesses the impact of missed insulin doses and prevalence of mistimed and reduced insulin doses and mild hypoglycemia in patients with type 2 diabetes treated with basal insulin analogues in Spain, and compares the data collected to pooled data from 8 other European countries (OECs). GAPP2 was an international, online, cross-sectional study of diabetic patients aged ≥40 years treated with long-acting insulin analogues and their healthcare professionals. Patients and healthcare professionals were recruited from online research panels. Data reported in Spain are compared to pooled data from 8 OECs. In Spain, 1-3% of patients reported they had reduced, missed, or mistimed at least one insulin does in the previous month. Significantly more OEC patients reported dosing irregularities (15-23%; all P<0.01). In Spain, 77% of patients were worried and 59% felt guilty for missing a dose of basal insulin, while 24% reported that they were very worried about nocturnal hypoglycemia. Significantly fewer OEC patients reported worrying (47%; P<0.01) and feeling guilty (37%; P<0.01) about missing an insulin dose, or worry about nocturnal hypoglycemia (12%; P<0.01). In Spain, patients with type 2 diabetes report fewer dosing irregularities and hypoglycemic episodes as compared to patients from OECs. However, Spanish patients appear to have a reduced quality of life related to hypoglycemia as well as worry and guilt related to insulin dosing irregularities. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

Estimation of endogenous glucose production during hyperinsulinemic-euglycemic glucose clamps. Comparison of unlabeled and labeled exogenous glucose infusates

International Nuclear Information System (INIS)

Finegood, D.T.; Bergman, R.N.; Vranic, M.

1987-01-01

Tracer methodology has been applied extensively to the estimation of endogenous glucose production (Ra) during euglycemic glucose clamps. The accuracy of this approach has been questioned due to the observation of significantly negative estimates for Ra when insulin levels are high. We performed hyperinsulinemic (300 microU/ml)-euglycemic glucose clamps for 180 min in normal dogs and compared the standard approach, an unlabeled exogenous glucose infusate (cold GINF protocol, n = 12), to a new approach in which a tracer (D-[3- 3 H]glucose) was added to the exogenous glucose used for clamping (hot GINF protocol, n = 10). Plasma glucose, insulin and glucagon concentrations, and glucose infusion rates were similar for the two protocols. Plasma glucose specific activity was 20 +/- 1% of basal (at 120-180 min) in the cold GINF studies, and 44 +/- 3 to 187 +/- 5% of basal in the hot GINF studies. With the one-compartment, fixed pool volume model of Steele, Ra for the cold GINF studies was -2.4 +/- 0.7 mg X min-1 X kg-1 at 25 min and remained significantly negative until 110 min (P less than .05). For the hot GINF studies, Ra was never significantly less than zero (P greater than .05) and was greater than in the cold GINF studies at 20-90 min (P less than .05). There was substantially less between-(78%) and within- (40%) experiment variation for the hot GINF studies compared with the cold GINF studies. An alternate approach (regression method) to the application of the one-compartment model, which allows for a variable and estimable effective distribution volume, yielded Ra estimates that were suppressed 60-100% from basal

Treating Severe Hypoglycemia: Rapid Mixing of Lyophilized Glucagon and Diluent at Point of Care With the Enject GlucaPen

OpenAIRE

Rylander, Dick

2014-01-01

Severe hypoglycemia (SH) is a common problem in type 1 diabetes (T1D). Annually, nearly 1 of 5 persons with long-standing T1D will have SH. Though injections of glucagon are effective in treating SH, liquid formulations of glucagon are biochemically very unstable. For this reason, available preparations of glucagon are lyophilized; the powder and the diluent must be mixed at the point of care prior to administration and any remaining drug must be discarded. The process of mixing and delivery ...

Blood Glucose Reduction by Diabetic Drugs with Minimal Hypoglycemia Risk for Cardiovascular Outcomes

DEFF Research Database (Denmark)

Huang, Chi-Jung; Wang, Wei-Ting; Sung, Shih-Hsien

2018-01-01

of antidiabetic drugs with less hypoglycemia risk were comprehensively searched in MEDLINE, Embase, and the Cochrane Library up to January 27, 2018. Mixed-effects meta-regression analysis was conducted to explore the relationship between haemoglobin A1c (HbA1c) reduction and the risk of major adverse...... concentration was 0.42% lower (median, 0.27-0.86%) for participants given antihyperglycemic agents than those given placebo. The meta-regression analysis demonstrated that HbA1c reduction was significantly associated with a decreased risk of MACE (β value, -0.39 to -0.55; P...-40%) for MACE. By contrast, the meta-regression analysis for trials using conventional agents failed to demonstrate a significant relationship between achieved HbA1c difference and MACE risk (P>0.74). CONCLUSIONS: Compared with placebo, newer T2D agents with less hypoglycemic hazard significantly reduced...

Atypical blood glucose response to continuous and interval exercise in a person with type 1 diabetes: a case report.

Science.gov (United States)

Moser, Othmar; Tschakert, Gerhard; Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R; Koehler, Gerd; Eckstein, Max L; Bracken, Richard M; Hofmann, Peter

2017-06-30

Therapy must be adapted for people with type 1 diabetes to avoid exercise-induced hypoglycemia caused by increased exercise-related glucose uptake into muscles. Therefore, to avoid hypoglycemia, the preexercise short-acting insulin dose must be reduced for safety reasons. We report a case of a man with long-lasting type 1 diabetes in whom no blood glucose decrease during different types of exercise with varying exercise intensities and modes was found, despite physiological hormone responses. A Caucasian man diagnosed with type 1 diabetes for 24 years performed three different continuous high-intensity interval cycle ergometer exercises as part of a clinical trial (ClinicalTrials.gov identifier NCT02075567). Intensities for both modes of exercises were set at 5% below and 5% above the first lactate turn point and 5% below the second lactate turn point. Short-acting insulin doses were reduced by 25%, 50%, and 75%, respectively. Measurements taken included blood glucose, blood lactate, gas exchange, heart rate, adrenaline, noradrenaline, cortisol, glucagon, and insulin-like growth factor-1. Unexpectedly, no significant blood glucose decreases were observed during all exercise sessions (start versus end, 12.97 ± 2.12 versus 12.61 ± 2.66 mmol L -1 , p = 0.259). All hormones showed the expected response, dependent on the different intensities and modes of exercises. People with type 1 diabetes typically experience a decrease in blood glucose levels, particularly during low- and moderate-intensity exercises. In our patient, we clearly found no decline in blood glucose, despite a normal hormone response and no history of any insulin insensitivity. This report indicates that there might be patients for whom the recommended preexercise therapy adaptation to avoid exercise-induced hypoglycemia needs to be questioned because this could increase the risk of severe hyperglycemia and ketosis.

Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia.

Science.gov (United States)

Abi-Saab, Walid M; Maggs, David G; Jones, Tim; Jacob, Ralph; Srihari, Vinod; Thompson, James; Kerr, David; Leone, Paola; Krystal, John H; Spencer, Dennis D; During, Matthew J; Sherwin, Robert S

2002-03-01

Brain levels of glucose and lactate in the extracellular fluid (ECF), which reflects the environment to which neurons are exposed, have never been studied in humans under conditions of varying glycemia. The authors used intracerebral microdialysis in conscious human subjects undergoing electrophysiologic evaluation for medically intractable epilepsy and measured ECF levels of glucose and lactate under basal conditions and during a hyperglycemia-hypoglycemia clamp study. Only measurements from nonepileptogenic areas were included. Under basal conditions, the authors found the metabolic milieu in the brain to be strikingly different from that in the circulation. In contrast to plasma, lactate levels in brain ECF were threefold higher than glucose. Results from complementary studies in rats were consistent with the human data. During the hyperglycemia-hypoglycemia clamp study the relationship between plasma and brain ECF levels of glucose remained similar, but changes in brain ECF glucose lagged approximately 30 minutes behind changes in plasma. The data demonstrate that the brain is exposed to substantially lower levels of glucose and higher levels of lactate than those in plasma; moreover, the brain appears to be a site of significant anaerobic glycolysis, raising the possibility that glucose-derived lactate is an important fuel for the brain.

Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis.

Science.gov (United States)

Buckingham, Bruce A; Raghinaru, Dan; Cameron, Fraser; Bequette, B Wayne; Chase, H Peter; Maahs, David M; Slover, Robert; Wadwa, R Paul; Wilson, Darrell M; Ly, Trang; Aye, Tandy; Hramiak, Irene; Clarson, Cheril; Stein, Robert; Gallego, Patricia H; Lum, John; Sibayan, Judy; Kollman, Craig; Beck, Roy W

2015-07-01

Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess the efficacy and safety of a continuous glucose monitor-based overnight predictive low-glucose suspend (PLGS) system. In two age-groups of children with type 1 diabetes (11-14 and 4-10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight. Median time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11-14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4-10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL [P < 0.001] and 153 ± 14 vs. 160 ± 16 mg/dL [P = 0.004], respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11-14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4-10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis. In 4-14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

EARS2 mutations cause fatal neonatal lactic acidosis, recurrent hypoglycemia and agenesis of corpus callosum.

Science.gov (United States)

Danhauser, Katharina; Haack, Tobias B; Alhaddad, Bader; Melcher, Marlen; Seibt, Annette; Strom, Tim M; Meitinger, Thomas; Klee, Dirk; Mayatepek, Ertan; Prokisch, Holger; Distelmaier, Felix

2016-06-01

Mitochondrial aminoacyl tRNA synthetases are essential for organelle protein synthesis. Genetic defects affecting the function of these enzymes may cause pediatric mitochondrial disease. Here, we report on a child with fatal neonatal lactic acidosis and recurrent hypoglycemia caused by mutations in EARS2, encoding mitochondrial glutamyl-tRNA synthetase 2. Brain ultrasound revealed agenesis of corpus callosum. Studies on patient-derived skin fibroblasts showed severely decreased EARS2 protein levels, elevated reactive oxygen species (ROS) production, and altered mitochondrial morphology. Our report further illustrates the clinical spectrum of the severe neonatal-onset form of EARS2 mutations. Moreover, in this case the live-cell parameters appeared to be more sensitive to mitochondrial dysfunction compared to standard diagnostics, which indicates the potential relevance of fibroblast studies in children with mitochondrial diseases.

Glucose levels in late preterm and term newborns at one hour of life and frequency of hypoglycemia

International Nuclear Information System (INIS)

Afzal, M.; Yaqoob, A.

2015-01-01

To determine glucose levels in late preterm and term newborns at one hour of life in our population, along with the frequency of symptomatic hypoglycemia and it's known risk factors. Study Design: Descriptive study Place and Duration of Study: Quaid-e-Azam International Hospital (QIH) Islamabad from July 2012 to September 2013. Material and Methods: Two hundred and seventy newborns were selected by consecutive purposive non probability sampling who were born at QIH either by spontaneous vaginal delivery or cesarean section. Only healthy neonates were included. Gestational age, weight, fetal and maternal risk factors were assessed. Glucose level was measured by glucometer at 1 hour of life after first feed. Neonates that became symptomatic with low glucose levels were thoroughly studied, readings reconfirmed from laboratory and were promptly managed. Results: Thirty (11%) babies showed sugar level < 30 mg/dl at 1 hour of life. Out of them 18(60%) were late preterm and 12(40%) were term babies. Out of them 12(40%) babies weighed <2kg, 8(26%) were between 2-2.5 kg and 6(20%) were 2.5-4.0 kg while 4(14%) babies were between 4.0 to 4.6 kg. Only 6(2.2%) newborns became symptomatic with low sugar level. Among symptomatic newnates, 4 mothers had gestational diabetes and other two were with pregnancy induced hypertension (PIH). Important risk factors were gestational diabetes, PIH, fetal distress and SGA babies. Safest lower glucose level was found to be 30 mg/dl at 1 hour after birth. Conclusion: Plasma glucose levels measured at 1 hour of life in late preterm and term newborns in our population are consistent with international studies. Frequency of ymptomatic hypoglycemia is quite low and normal newborns without risk factors do not need screening. However one needs to be vigilant in babies with risk factors. (author)

Hepatic Insulin Resistance and Altered Gluconeogenic Pathway in Premature Baboons.

Science.gov (United States)

McGill-Vargas, Lisa; Gastaldelli, Amalia; Liang, Hanyu; Anzueto Guerra, Diana; Johnson-Pais, Teresa; Seidner, Steven; McCurnin, Donald; Muscogiuri, Giovanna; DeFronzo, Ralph; Musi, Nicolas; Blanco, Cynthia

2017-05-01

Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extrauterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content, and gene expression of key insulin-signaling/gluconeogenic molecules. Fetal baboons were delivered at 67%, 75%, and term gestational age and euthanized at birth. Neonatal baboons were delivered prematurely (67% gestation), survived for two weeks, and compared with similar postnatal term animals and underwent serial hyperinsulinemic-euglycemic clamp studies. Premature baboons had decreased endogenous glucose production (EGP) compared with term animals. Consistent with these results, the gluconeogenic molecule, phosphoenolpyruvate carboxykinase messenger RNA, was decreased in preterm baboons compared with terms. Hepatic insulin signaling was altered by preterm birth as evidenced by decreased insulin receptor-β, p85 subunit of phosphoinositide 3-kinase, phosphorylated insulin receptor substrate 1, and Akt-1 under insulin-stimulated conditions. Furthermore, preterm baboons failed to have the normal increase in glycogen synthase kinase-α from fetal to postnatal life. The blunted responses in hepatic insulin signaling may contribute to the hyperglycemia of prematurity, while impaired EGP leads to hypoglycemia of prematurity. Copyright © 2017 Endocrine Society.

In vivo measurements of brain glucose transport using the reversible michaelis-menten model and simultaneous measurements of cerebral blood flow changes during hypoglycemia

OpenAIRE

Choi, I.-Y.; Lee, S.-P.; Kim, S.-G.; Gruetter, R.

2001-01-01

Glucose is the major substrate that sustains normal brain function. When the brain glucose concentration approaches zero, glucose transport across the blood-brain barrier becomes rate limiting for metabolism during, for example, increased metabolic activity and hypoglycemia. Steady-state brain glucose concentrations in α-chloralose anesthetized rats were measured noninvasively as a function of plasma glucose. The relation between brain and plasma glucose was linear at 4.5 to 30 mmol/L plasma ...

Comparison of appetite responses to high- and low-glycemic index postexercise meals under matched insulinemia and fiber in type 1 diabetes.

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Campbell, Matthew D; Gonzalez, Javier T; Rumbold, Penny L S; Walker, Mark; Shaw, James A; Stevenson, Emma J; West, Daniel J

2015-03-01

Patients with type 1 diabetes face heightened risk of hypoglycemia after exercise. Subsequent overfeeding, as a preventative measure against hypoglycemia, negates the energy deficit after exercise. Patients are also required to reduce the insulin dose administered with postexercise foods to further combat hypoglycemia. However, the insulin dose is dictated solely by the carbohydrate content, even though postprandial glycemia is vastly influenced by glycemic index (GI). With a need to control the postexercise energy balance, appetite responses after meals differing in GI are of particular interest. We assessed the appetite response to low-glycemic index (LGI) and high-glycemic index (HGI) postexercise meals in type 1 diabetes patients. This assessment also offered us the opportunity to evaluate the influence of GI on appetite responses independently of insulinemia, which confounds findings in individuals without diabetes. Ten physically active men with type 1 diabetes completed 2 trials in a randomized crossover design. After 45 min of treadmill exercise at 70% of the peak oxygen uptake, participants consumed an LGI (GI ∼37) or HGI (GI ∼92) meal with a matched macronutrient composition, negligible fiber content, and standardized insulin-dose administration. The postprandial appetite response was determined for 180 min postmeal. During this time, circulating glucose, insulin, glucagon, and glucagon-like peptide-1 (GLP-1) concentrations and subjective appetite ratings were determined. The HGI meal produced an ∼60% greater postprandial glucose area under the curve (AUC) than did the LGI meal (P = 0.008). Insulin, glucagon, and GLP-1 did not significantly differ between trials (P > 0.05). The fullness AUC was ∼25% greater after the HGI meal than after the LGI meal (P < 0.001), whereas hunger sensations were ∼9% lower after the HGI meal than after the LGI meal (P = 0.001). Under conditions of matched insulinemia and fiber, an HGI postexercise meal suppresses

Stigma and Its Association With Glycemic Control and Hypoglycemia in Adolescents and Young Adults With Type 1 Diabetes: Cross-Sectional Study.

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Brazeau, Anne-Sophie; Nakhla, Meranda; Wright, Michael; Henderson, Mélanie; Panagiotopoulos, Constadina; Pacaud, Daniele; Kearns, Patricia; Rahme, Elham; Da Costa, Deborah; Dasgupta, Kaberi

2018-04-20

Qualitative studies in type 1 diabetes indicate that visibility of diabetes supplies, self-care, and hypoglycemia symptoms are associated with stigma and suboptimal management. This may be particularly salient in youth who face concurrent challenges such as establishing autonomy and making vocational choices. The aim of the study was to estimate stigma prevalence in youth (aged 14-24 years) with type 1 diabetes and its associations with glycemic control. Participants, recruited largely through social media, were asked to complete a Web-based survey and to send via mail capillary blood samples for glycated hemoglobin (HbA 1c ) measurement. The primary definition of stigma required endorsement of one or more of 3 stigma-specific items of the Barriers to Diabetes Adherence questionnaire. These addressed avoidance of diabetes management with friends present, difficulty telling others about diabetes diagnosis, and embarrassment in performing diabetes care with others present. Poor glycemic control was defined as HbA 1c >9% (ie, >75 mmol/mol; measured value when available, else self-report) and/or ≥1 severe hypoglycemic episode in the previous year (reported requiring assistance from someone else during the episode). Stigma prevalence was computed (95% CI), and associations with glycemic control were evaluated (multivariate logistic regression models). Among the 380 respondents, stigma prevalence was 65.5% (95% CI 60.7-70.3). Stigma was associated with a 2-fold higher odds of poor glycemic control overall (odds ratio [OR] 2.25, 95% CI 1.33-3.80; adjusted for age, sex, and type of treatment). There were specific associations with both HbA 1c >9% (75 mmol/mol; OR 3.05, 95% CI 1.36-6.86) and severe hypoglycemia in the previous year (OR 1.86, 95% CI 1.05-3.31). There is a high prevalence of stigma in youth with type 1 diabetes that is associated with both elevated HbA 1c levels and severe hypoglycemia. Targeted strategies to address stigma are needed. Clinical

Glycemia, Hypoglycemia, and Costs of Simultaneous Islet-Kidney or Islet After Kidney Transplantation Versus Intensive Insulin Therapy and Waiting List for Islet Transplantation.

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Gerber, Philipp A; Locher, Rebecca; Zuellig, Richard A; Tschopp, Oliver; Ajdler-Schaeffler, Evelyne; Kron, Philipp; Oberkofler, Christian; Brändle, Michael; Spinas, Giatgen A; Lehmann, Roger

2015-10-01

Long-term data of patients with type 1 diabetes mellitus (T1D) after simultaneous islet-kidney (SIK) or islet-after-kidney transplantation (IAK) are rare and have never been compared to intensified insulin therapy (IIT). Twenty-two patients with T1D and end-stage renal failure undergoing islet transplantation were compared to 70 patients matched for age and diabetes duration treated with IIT and to 13 patients with kidney transplantation alone or simultaneous pancreas-kidney after loss of pancreas function (waiting list for IAK [WLI]). Glycemic control, severe hypoglycemia, insulin requirement, and direct medical costs were analyzed. Glycated hemoglobin decreased significantly from 8.2 ± 1.5 to 6.7 ± 0.9% at the end of follow-up (mean 7.2 ± 2.5 years) in the SIK/IAK and remained constant in IIT (7.8 ± 1.0% and 7.6 ± 1.0) and WLI (7.8 ± 0.8 and 7.9 ± 1.0%). Daily insulin requirement decreased from 0.53 ± 0.15 to 0.29 ± 0.26 U/kg and remained constant in IIT (0.59 ± 0.19 and 0.58 ± 0.23 U/kg) and in WLI (0.76 ± 0.28 and 0.73 ± 0.11 U/kg). Severe hypoglycemia dropped in SIK/IAK from 4.5 ± 9.7 to 0.3 ± 0.7/patient-year and remained constant in IIT (0.1 ± 0.7 and 0.2 ± 0.8/patient-year). Detailed cost analysis revealed US $57,525 of additional cost for islet transplantation 5 years after transplantation. Based on a 5- and 10-year analysis, cost neutrality is assumed to be achieved 15 years after transplantation. This long-term cohort with more than 7 years of follow-up shows that glycemic control in patients with T1D after SIK/IAK transplantation improved, and the rate of severe hypoglycemia decreased significantly as compared to control groups. Cost analysis revealed that islet transplantation is estimated to be cost neutral at 15 years after transplantation.

[Diabetes care and incidence of severe hypoglycemia in nursing home facilities and nursing services: The Heidelberg Diabetes Study].

Science.gov (United States)

Bahrmann, A; Wörz, E; Specht-Leible, N; Oster, P; Bahrmann, P

2015-04-01

The goal of this study was to perform a structured analysis of the treatment quality and acute complications of geriatric patients with diabetes mellitus (DM) cared for by nursing services and nursing home facilities. Secondly, structural problems and potentials for improvement in the care of multimorbid older people with DM treated by nursing homes and nursing services were analysed from the viewpoint of geriatric nurses, managers of nursing homes and general practitioners. In all, 77 older persons with DM from 13 nursing homes and 3 nursing services were included in the analysis (76.6% female, HbA1c 6.9 ± 1.4%, age 81.6 ± 9.9 years). Structural problems and potentials for improvement were collected from 95 geriatric nurses, 9 managers of nursing homes and 6 general practitioners using semistandardized questionnaires. Metabolic control was too strict in care-dependent older people with DM (mean HbA1c value: 6.9 ± 1.4 %; recommended by guidelines: 7-8%). The measurement of HbA1c was performed in 16 of 77 people (20.8%) within the last year despite a high visitation frequency of the general practitioners (12.7 ± 7.7 within the last 6 months). The incidence of severe hypoglycemia was 7.8%/patient/year. Regarding the management in case of diabetes-related acute complications 33 geriatric nurses (34.7%) stated not having any written standard (nursing home 39%, geriatric services 16.7%). Complex insulin therapies are still used in older people with DM with the consequence of a high incidence of severe hypoglycemia. Concrete management standards in the case of diabetes-related acute complications for geriatric nurses are lacking for more than one third of the nursing services.

Infectious Diseases,

Science.gov (United States)

1980-02-29

of sufficient severity, infectious hepatitis may produce hypoglycemia or hepatic failure. Severe hypoglycemia is also a common danger in neonatal ...emergency situations geoier~3ly involve the correction of severe fluid and electrolyte or acid-base ;atbnormalities. Severe hypoglycemia or anoxia... causes widespread metabolic responses in the host and in addition, leads to nutritional deficiencies. Localized infections may also result in metabolic

Are Changes in Heart Rate Variability During Hypoglycemia Confounded by the Presence of Cardiovascular Autonomic Neuropathy in Patients with Diabetes?

DEFF Research Database (Denmark)

Cichosz, Simon Lebech; Frystyk, Jan; Tarnow, Lise

2017-01-01

BACKGROUND: We have recently shown how the combination of information from continuous glucose monitor (CGM) and heart rate variability (HRV) measurements can be used to construct an algorithm for prediction of hypoglycemia in both bedbound and active patients with type 1 diabetes (T1D). Questions...... with CGM and a Holter device while they performed normal daily activities. CAN was diagnosed using two cardiac reflex tests: (1) deep breathing and (2) orthostatic hypotension and end organ symptoms. Early CAN was defined as the presence of one abnormal reflex test and severe CAN was defined as two...

Endocrine and metabolic emergencies in children: hypocalcemia, hypoglycemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis

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Se Young Kim

2015-12-01

Full Text Available It is important to fast diagnosis and management of the pediatric patients of the endocrine metabolic emergencies because the signs and symptoms of these disorders are nonspecific. Delayed diagnosis and treatment may lead to serious consequences of the pediatric patients, for example, cerebral dysfunction leading to coma or death of the patients with hypoglycemia, hypocalcemia, adrenal insufficiency, or diabetic ketoacidosis. The index of suspicion of the endocrine metabolic emergencies should be preceded prior to the starting nonspecific treatment. Importantly, proper diagnosis depends on the collection of blood and urine specimen before nonspecific therapy (intravenous hydration, electrolytes, glucose or calcium injection. At the same time, the taking of precise history and searching for pathognomonic physical findings should be performed. This review was described for fast diagnosis and proper management of hypoglycemic emergencies, hypocalcemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis.

A Critical Role of Fatty Acid Binding Protein 4 and 5 (FABP4/5) in the Systemic Response to Fasting

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Syamsunarno, Mas Rizky A. A.; Iso, Tatsuya; Hanaoka, Hirofumi; Yamaguchi, Aiko; Obokata, Masaru; Koitabashi, Norimichi; Goto, Kosaku; Hishiki, Takako; Nagahata, Yoshiko; Matsui, Hiroki; Sano, Motoaki; Kobayashi, Masaki; Kikuchi, Osamu; Sasaki, Tsutomu; Maeda, Kazuhisa; Murakami, Masami; Kitamura, Tadahiro; Suematsu, Makoto; YoshitoTsushima; Endo, Keigo; Hotamisligil, Gökhan S.; Kurabayashi, Masahiko

2013-01-01

During prolonged fasting, fatty acid (FA) released from adipose tissue is a major energy source for peripheral tissues, including the heart, skeletal muscle and liver. We recently showed that FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipocytes and macrophages, are prominently expressed in capillary endothelial cells in the heart and skeletal muscle. In addition, mice deficient for both FABP4 and FABP5 (FABP4/5 DKO mice) exhibited defective uptake of FA with compensatory up-regulation of glucose consumption in these tissues during fasting. Here we showed that deletion of FABP4/5 resulted in a marked perturbation of metabolism in response to prolonged fasting, including hyperketotic hypoglycemia and hepatic steatosis. Blood glucose levels were reduced, whereas the levels of non-esterified FA (NEFA) and ketone bodies were markedly increased during fasting. In addition, the uptake of the 125I-BMIPP FA analogue in the DKO livers was markedly increased after fasting. Consistent with an increased influx of NEFA into the liver, DKO mice showed marked hepatic steatosis after a 48-hr fast. Although gluconeogenesis was observed shortly after fasting, the substrates for gluconeogenesis were reduced during prolonged fasting, resulting in insufficient gluconeogenesis and enhanced hypoglycemia. These metabolic responses to prolonged fasting in DKO mice were readily reversed by re-feeding. Taken together, these data strongly suggested that a maladaptive response to fasting in DKO mice occurred as a result of an increased influx of NEFA into the liver and pronounced hypoglycemia. Together with our previous study, the metabolic consequence found in the present study is likely to be attributed to an impairment of FA uptake in the heart and skeletal muscle. Thus, our data provided evidence that peripheral uptake of FA via capillary endothelial FABP4/5 is crucial for systemic metabolism and may establish FABP4/5 as potentially novel targets for the

Identification of outliers and positive deviants for healthcare improvement: looking for high performers in hypoglycemia safety in patients with diabetes

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Brigid Wilson

2017-11-01

Full Text Available Abstract Background The study objectives were to determine: (1 how statistical outliers exhibiting low rates of diabetes overtreatment performed on a reciprocal measure – rates of diabetes undertreatment; and (2 the impact of different criteria on high performing outlier status. Methods The design was serial cross-sectional, using yearly Veterans Health Administration (VHA administrative data (2009–2013. Our primary outcome measure was facility rate of HbA1c overtreatment of diabetes in patients at risk for hypoglycemia. Outlier status was assessed by using two approaches: calculating a facility outlier value within year, comparator group, and A1c threshold while incorporating at risk population sizes; and examining standardized model residuals across year and A1c threshold. Facilities with outlier values in the lowest decile for all years of data using more than one threshold and comparator or with time-averaged model residuals in the lowest decile for all A1c thresholds were considered high performing outliers. Results Using outlier values, three of the 27 high performers from 2009 were also identified in 2010–2013 and considered outliers. There was only modest overlap between facilities identified as top performers based on three thresholds: A1c  9% than VA average in the population of patients at high risk for hypoglycemia. Conclusions Statistical identification of positive deviants for diabetes overtreatment was dependent upon the specific measures and approaches used. Moreover, because two facilities may arrive at the same results via very different pathways, it is important to consider that a “best” practice may actually reflect a separate “worst” practice.

Effects of 7 days of exercise training on insulin sensitivity and responsiveness in type 2 diabetes mellitus

DEFF Research Database (Denmark)

Kirwan, John P; Solomon, Thomas; Wojta, Daniel M

2009-01-01

sensitivity and responsiveness and 2) short-term exercise training results in improved suppression of hepatic glucose production by insulin. Fourteen obese patients with type 2 diabetes, age 64 +/- 2 yr, underwent a two-stage hyperinsulinemic euglycemic clamp procedure, first stage 40 mU.m(-2).min(-1) insulin......The objectives of this study were to determine whether 1) the improvement in insulin action induced by short-term exercise training in patients with type 2 diabetes is due to an improvement in insulin sensitivity, an improvement in insulin responsiveness, or a combination of improved insulin...... infusion, second stage 1,000 mU.m(-2).min(-1) insulin infusion, together with a [3-(3)H]glucose infusion, before and after 7 days of exercise. The training consisted of 30 min of cycling and 30 min of treadmill walking at approximately 70% of maximal aerobic capacity daily for 7 days. The exercise program...

The GLP-1 Analogue Exenatide Improves Hepatic and Muscle Insulin Sensitivity in Diabetic Rats: Tracer Studies in the Basal State and during Hyperinsulinemic-Euglycemic Clamp

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Hui Wu

2014-01-01

Full Text Available Objective. Glucagon-like peptide-1 (GLP-1 analogues (e.g., exenatide increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues. Methods. Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C; nondiabetic + exenatide (C + E; diabetic (D; diabetic + exenatide (D + E with diabetes induced by streptozotocin and high fat diet. Infusion of 3-3H-glucose and U-13C-glycerol was used to measure basal rates of appearance (Ra of glucose and glycerol and gluconeogenesis from glycerol (GNG. During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-14C-glucose. Results. In the diabetic rats, exenatide reduced the basal Ra of glucose (P<0.01 and glycerol (P<0.01 and GNG (P<0.001. During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P<0.01 during the clamp. In the nondiabetic rats, exenatide had no effect. Conclusion. In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.

The adipose transcriptional response to insulin is determined by obesity, not insulin sensitivity

DEFF Research Database (Denmark)

Rydén, Mikael; Hrydziuszko, Olga; Mileti, Enrichetta

2016-01-01

Metabolically healthy obese subjects display preserved insulin sensitivity and a beneficial white adipose tissue gene expression pattern. However, this observation stems from fasting studies when insulin levels are low. We investigated adipose gene expression by 5'Cap-mRNA sequencing in 17 healthy...... non-obese (NO), 21 insulin-sensitive severely obese (ISO), and 30 insulin-resistant severely obese (IRO) subjects, before and 2 hr into a hyperinsulinemic euglycemic clamp. ISO and IRO subjects displayed a clear but globally similar transcriptional response to insulin, which differed from the small...... effects observed in NO subjects. In the obese, 231 genes were altered; 71 were enriched in ISO subjects (e.g., phosphorylation processes), and 52 were enriched in IRO subjects (e.g., cellular stimuli). Common cardio-metabolic risk factors and gender do not influence these findings. This study demonstrates...

Fasting mediated increase in p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex of mice.

Science.gov (United States)

Pitchaimani, Vigneshwaran; Arumugam, Somasundaram; Thandavarayan, Rajarajan Amirthalingam; Karuppagounder, Vengadeshprabhu; Sreedhar, Remya; Afrin, Rejina; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Nomoto, Mayumi; Sone, Hirohito; Suzuki, Kenji; Watanabe, Kenichi

2014-09-05

BAD-deficient mice and fasting have several common functional roles in seizures, beta-hydroxybutyrate (BHB) uptake in brain and alteration in counterregulatory hormonal regulation during hypoglycemia. Neuronal specific insulin receptor knockout (NIRKO) mice display impaired counterregulatory hormonal responses during hypoglycemia. In this study we investigated the fasting mediated expression of p-BAD(ser155) and p-AKT(ser473) in different regions of brain (prefrontal cortex, hippocampus, midbrain and hypothalamus). Fasting specifically increases p-BAD(ser155) and p-AKT(ser473) in prefrontal cortex and decreases in other regions of brain. Our results suggest that fasting may increase the uptake BHB by decreasing p-BAD(ser155) in the brain during hypoglycemia except prefrontal cortex and it uncovers specific functional area of p-BAD(ser155) and p-AKT(ser473) that may regulates counter regulatory hormonal response. Overall in support with previous findings, fasting mediated hypoglycemia activates prefrontal cortex insulin signaling which influences the hypothalamic paraventricular nucleus mediated activation of sympathoadrenal hormonal responses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Glucose counterregulation in diabetes secondary to chronic pancreatitis

DEFF Research Database (Denmark)

Larsen, S; Hilsted, J; Philipsen, E K

1990-01-01

Glucose counterregulation and hormonal responses after insulin-induced hypoglycemia were investigated in six patients with diabetes mellitus secondary to chronic pancreatitis, in seven with insulin-dependent (type I) diabetes mellitus, and in seven healthy subjects. Glucose counterregulation...... was identical in type I patients and in the patients with chronic pancreatitis, whereas both groups had impaired glucose recovery compared with the healthy subjects. The patients with chronic pancreatitis had no glucagon response to hypoglycemia, whereas epinephrine increased significantly. In an additional...... experiment, glucose recovery did not occur after hypoglycemia during concomitant beta-adrenoceptor blockade in these patients. In conclusion, glucose counterregulation is preserved but slightly impaired in patients with diabetes secondary to chronic pancreatitis, and the combination of total glucagon...

A K ATP channel-dependent pathway within alpha cells regulates glucagon release from both rodent and human islets of Langerhans.

Science.gov (United States)

MacDonald, Patrick E; De Marinis, Yang Zhang; Ramracheya, Reshma; Salehi, Albert; Ma, Xiaosong; Johnson, Paul R V; Cox, Roger; Eliasson, Lena; Rorsman, Patrik

2007-06-01

Glucagon, secreted from pancreatic islet alpha cells, stimulates gluconeogenesis and liver glycogen breakdown. The mechanism regulating glucagon release is debated, and variously attributed to neuronal control, paracrine control by neighbouring beta cells, or to an intrinsic glucose sensing by the alpha cells themselves. We examined hormone secretion and Ca(2+) responses of alpha and beta cells within intact rodent and human islets. Glucose-dependent suppression of glucagon release persisted when paracrine GABA or Zn(2+) signalling was blocked, but was reversed by low concentrations (1-20 muM) of the ATP-sensitive K(+) (KATP) channel opener diazoxide, which had no effect on insulin release or beta cell responses. This effect was prevented by the KATP channel blocker tolbutamide (100 muM). Higher diazoxide concentrations (>/=30 muM) decreased glucagon and insulin secretion, and alpha- and beta-cell Ca(2+) responses, in parallel. In the absence of glucose, tolbutamide at low concentrations (10 muM) were inhibitory. In the presence of a maximally inhibitory concentration of tolbutamide (0.5 mM), glucose had no additional suppressive effect. Downstream of the KATP channel, inhibition of voltage-gated Na(+) (TTX) and N-type Ca(2+) channels (omega-conotoxin), but not L-type Ca(2+) channels (nifedipine), prevented glucagon secretion. Both the N-type Ca(2+) channels and alpha-cell exocytosis were inactivated at depolarised membrane potentials. Rodent and human glucagon secretion is regulated by an alpha-cell KATP channel-dependent mechanism. We propose that elevated glucose reduces electrical activity and exocytosis via depolarisation-induced inactivation of ion channels involved in action potential firing and secretion.

High rate of hypoglycemia in 6770 type 2 diabetes patients with comorbid dementia: A multicenter cohort study on 215,932 patients from the German/Austrian diabetes registry.

Science.gov (United States)

Prinz, Nicole; Stingl, Julia; Dapp, Albrecht; Denkinger, Michael D; Fasching, Peter; Jehle, Peter M; Merger, Sigrun; Mühldorfer, Steffen; Pieper, Urte; Schuler, Andreas; Zeyfang, Andrej; Holl, Reinhard W

2016-02-01

Dementia and type 2 diabetes (T2D) are two major phenomena in older people. To compare anti-hyperglycemic therapy and diabetes-related comorbidities between elderly T2D patients with or without comorbid dementia. 215,932 type 2 diabetes patients aged ≥ 40 years (median [Q1;Q3]: 70.4 [61.2;77.7] years) from the standardized, multicenter German/Austrian diabetes patient registry, DPV, were studied. To identify patients with comorbid dementia, the registry was searched by ICD-10 codes, DSM-IV/-5 codes, respective search terms and/or disease-specific medication. For group comparisons, multiple hierarchic regression modeling with adjustments for age, sex, and duration of diabetes was applied. 3.1% (n=6770; 57% females) of the eligible T2D patients had clinically recognized comorbid dementia. After adjustment for demographics, severe hypoglycemia (insulin group: 14.8 ± 0.6 vs. 10.4 ± 0.2 events per 100 patient-years, p<0.001), hypoglycemia with coma (insulin group: 7.6 ± 0.4 vs. 3.9 ± 0.1 events per 100 patient-years, p<0.001), depression (9.9 vs. 4.7%, p<0.001), hypertension (74.7 vs. 72.2%, p<0.001), stroke (25.3 vs. 6.5%, p<0.001), diabetic foot syndrome (6.0 vs. 5.2%, p=0.004), and microalbuminuria (34.7 vs. 32.2%, p<0.001) were more common in dementia patients compared to T2D without dementia. Moreover, patients with dementia received insulin therapy more frequently (59.3 vs. 54.7%, p<0.001), but metabolic control (7.7 ± 0.1 vs. 7.7 ± 0.1%) was comparable to T2D without dementia. In T2D with dementia, higher rates of hypoglycemia and other diabetes-related comorbidities were observed. Hence, the risks of a glucocentric and intense diabetes management with insulin and a focus on tight glycemic control without considering other factors may outweigh the benefits in elderly T2D patients with comorbid dementia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Diabetes and driving safety: science, ethics, legality and practice.

Science.gov (United States)

Cox, Daniel J; Singh, Harsimran; Lorber, Daniel

2013-04-01

Diabetes affects over 25 million people in the United States, most of whom are over the age of 16 and many of whom are licensed to drive a motor vehicle. Safe operation of a motor vehicle requires complex interactions of cognitive and motor functions and medical conditions that affect these functions often will increase the risk of motor vehicle accidents (MVA). In the case of diabetes, hypoglycemia is the most common factor that has been shown to increase MVA rates. When people with diabetes are compared with nondiabetic controls, systematic analyses show that the relative risk of MVA is increased by between 12% and 19% (Relative Risk Ratio 1.12-1.19). In comparison, the RRR for attention deficit hyperactivity disorder is 4.4 and for sleep apnea is 2.4. Epidemiologic research suggests that patients at risk for hypoglycemia-related MVAs may have some characteristics in common, including a history of severe hypoglycemia or of hypoglycemia-related driving mishaps. Experimental studies also have shown that people with a history of hypoglycemia-related driving mishaps have abnormal counter-regulatory responses to hypoglycemia and greater cognitive impairments during moderate hypoglycemia.

[Hemodynamic changes in hypoglycemic shock].

Science.gov (United States)

Gutiérrez, C; Piza, R; Chousleb, A; Hidalgo, M A; Ortigosa, J L

1977-01-01

Severe hypoglycemia may be present in seriously ill patients; if it is not corrected opportunely a series of neuroendocrinal mechanisms take place aimed at correcting metabolic alterations. These mechanisms can produce hemodynamic alterations as well. Nine mongrel dogs were studied with continuous registration of: blood pressure, central venous pressure, cardiac frequency, respiratory frequency, electrocardiogram and first derivative (Dp/Dt). Six dogs received crystalline (fast acting) insuline intravenously (group 1). After hemodynamic changes were registered hypoglycemia was corrected with 50 per cent glucose solution. Complementary insuline doses were administered to three dogs (group 2); in this group hypoglycemia was not corrected. In group 1 during hypoglycemia there was an increase in blood pressure, central venous pressure, cardiac frequency, respiratory frequency and Dp/Dt, and changes in QT and T wave on the EKG; these changes were partially reversible after hypoglycemia was corrected. The above mentioned alterations persisted in group 2, breathing became irregular irregular and respiratory arrest supervened. It can be inferred that the hemodynamic response to hypoglycemia is predominantly adrenergic. The role of catecolamines, glucocorticoides, glucagon, insuline, cyclic AMP in metabolic and hemodynamic alterations consecutive to hypoglycemia are discussed.

A psychometric evaluation of the Diabetes Symptom Checklist-Revised (DSC-R cognitive distress, fatigue, hyperglycemia, and hypoglycemia subscales in patients with type 1 and type 2 diabetes

Directory of Open Access Journals (Sweden)

Naegeli AN

2010-03-01

Full Text Available April N Naegeli1, Timothy E Stump2, Risa P Hayes11Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 2Consultant, Indianapolis, IN, USAObjective: To explore the use of Diabetes Symptom Checklist-Revised (DSC-R Cognitive Distress, Fatigue, Hyperglycemia, and Hypoglycemia subscales as measures of acute diabetesassociated symptoms in patients with both type 1 and 2 diabetes.Research design and methods: Our study was conducted in context of two international, multicenter, randomized clinical trials for inhaled insulin. Confirmatory factor analyses and assessments of reliability and construct validity were performed.Results: Study participants were 371 patients with type 2 (56% male; mean age, 57 years and 481 with type 1 diabetes (57% male, mean age, 40 years. In both populations a four-factor model was the best fit. Cronbach’s α ≥ 0.79 and intraclass correlation coefficient ≥0.63; subscales correlated (P ≤ 0.05 with measures of well-being and satisfaction (0.12 ≤ r ≤ 0.71. In patients with type 1 diabetes, three subscales correlated (P < 0.05 with A1C.Conclusions: The psychometric properties of the DSC-R Cognitive Distress, Fatigue, Hyperglycemia, and Hypoglycemia suggest they may be utilized in clinical trials as reliable and valid measures of acute symptoms of diabetes.Keywords: Diabetes Symptom Checklist-Revised, DSC-R, type 1 diabetes, type 2 diabetes, psychometric validation

Changes by short-term hypoxia in the membrane properties of pyramidal cells and the levels of purine and pyrimidine nucleotides in slices of rat neocortex; effects of agonists and antagonists of ATP-dependent potassium channels.

Science.gov (United States)

Pissarek, M; Garcia de Arriba, S; Schäfer, M; Sieler, D; Nieber, K; Illes, P

1998-10-01

In a first series of experiments, intracellular recordings were made from pyramidal cells in layers II-III of the rat primary somatosensory cortex. Superfusion of the brain slice preparations with hypoxic medium (replacement of 95%O2-5%CO2 with 95%N2-5%CO2) for up to 30 min led to a time-dependent depolarization (HD) without a major change in input resistance. Short periods of hypoxia (5 min) induced reproducible depolarizations which were concentration-dependently depressed by an agonist of ATP-dependent potassium (K(ATP)) channels, diazoxide (3-300 microM). The effect of 30 but not 300 microM diazoxide was reversed by washout. Tolbutamide (300 microM), an antagonist of K(ATP) channels, did not alter the HD when given alone. It did, however, abolish the inhibitory effect of diazoxide (30 microM) on the HD. Neither diazoxide (3-300 microM) nor tolbutamide (300 microM) influenced the membrane potential or the apparent input resistance of the neocortical pyramidal cells. Current-voltage (I-V) curves constructed at a membrane potential of -90 mV by injecting both de- and hyperpolarizing current pulses were not altered by diazoxide (30 microM) or tolbutamide (300 microM). Moreover, normoxic and hypoxic I-V curves did not cross each other, excluding a reversal of the HD at any membrane potential between -130 and -50 mV. The hypoxia-induced change of the I-V relation was the same both in the absence and presence of tolbutamide (300 microM). In a second series of experiments, nucleoside di- and triphosphates separated with anion exchange HPLC were measured in the neocortical slices. After 5 min of hypoxia, levels of nucleoside triphosphates declined by 29% (GTP), 34% (ATP), 44% (UTP) and 58% (CTP). By contrast, the levels of nucleoside diphosphates either did not change (UDP) or increased by 13% (GDP) and 40% (ADP). In slices subjected to 30 min of hypoxia the triphosphate levels continued to decrease, while the levels of GDP and ADP returned to control values. The tri

Insulin-resistant glucose metabolism in patients with microvascular angina--syndrome X

DEFF Research Database (Denmark)

Vestergaard, H; Skøtt, P; Steffensen, R

1995-01-01

Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose challenge, suggesting insulin resistance and a role for increased serum insulin in coronary microvascular dysfunction. The aim of the present study was to exa......Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose challenge, suggesting insulin resistance and a role for increased serum insulin in coronary microvascular dysfunction. The aim of the present study...... was to examine whether patients with MA are insulin-resistant. Nine patients with MA and seven control subjects were studied. All were sedentary and glucose-tolerant. Coronary arteriography was normal in all participants, and exercise-induced coronary ischemia was demonstrated in all MA patients. A euglycemic...... metabolism (8.4 +/- 0.9 v 12.5 +/- 1.3 mg.kg FFM-1.min-1, P

Common variants in the hERG (KCNH2) voltage-gated potassium channel are associated with altered fasting and glucose-stimulated plasma incretin and glucagon responses

DEFF Research Database (Denmark)

Engelbrechtsen, Line; Mahendran, Yuvaraj; Jonsson, Anna

2018-01-01

BACKGROUND: Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused by a dysfun......BACKGROUND: Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused...... by a dysfunctional Kv11.1 voltage-gated potassium channel. Based on these findings in patients with rare variants in hERG, we hypothesized that common variants in hERG may also lead to alterations in glucose homeostasis. Subsequently, we aimed to evaluate the effect of two common gain-of-function variants in hERG...... in hERG on QT-interval and circulation levels of incretins, insulin and glucagon. The Danish population-based Inter99 cohort (n = 5895) was used to assess the effect of common variants on QT-interval. The Danish ADDITION-PRO cohort was used (n = 1329) to study genetic associations with levels of GLP-1...

A liver-specific defect of Acyl-CoA degradation produces hyperammonemia, hypoglycemia and a distinct hepatic Acyl-CoA pattern.

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Nicolas Gauthier

Full Text Available Most conditions detected by expanded newborn screening result from deficiency of one of the enzymes that degrade acyl-coenzyme A (CoA esters in mitochondria. The role of acyl-CoAs in the pathophysiology of these disorders is poorly understood, in part because CoA esters are intracellular and samples are not generally available from human patients. We created a mouse model of one such condition, deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase (HL, in liver (HLLKO mice. HL catalyses a reaction of ketone body synthesis and of leucine degradation. Chronic HL deficiency and acute crises each produced distinct abnormal liver acyl-CoA patterns, which would not be predictable from levels of urine organic acids and plasma acylcarnitines. In HLLKO hepatocytes, ketogenesis was undetectable. Carboxylation of [2-(14C] pyruvate diminished following incubation of HLLKO hepatocytes with the leucine metabolite 2-ketoisocaproate (KIC. HLLKO mice also had suppression of the normal hyperglycemic response to a systemic pyruvate load, a measure of gluconeogenesis. Hyperammonemia and hypoglycemia, cardinal features of many inborn errors of acyl-CoA metabolism, occurred spontaneously in some HLLKO mice and were inducible by administering KIC. KIC loading also increased levels of several leucine-related acyl-CoAs and reduced acetyl-CoA levels. Ultrastructurally, hepatocyte mitochondria of KIC-treated HLLKO mice show marked swelling. KIC-induced hyperammonemia improved following administration of carglumate (N-carbamyl-L-glutamic acid, which substitutes for the product of an acetyl-CoA-dependent reaction essential for urea cycle function, demonstrating an acyl-CoA-related mechanism for this complication.

Developing an Integrated Treatment Pathway for a Post-Coronary Artery Bypass Grating (CABG) Geriatric Patient with Comorbid Hypertension and Type 1 Diabetes Mellitus for Treating Acute Hypoglycemia and Electrolyte Imbalance.

Science.gov (United States)

Naqvi, Atta Abbas; Shah, Amna; Ahmad, Rizwan; Ahmad, Niyaz

2017-01-01

The ailments afflicting the elderly population is a well-defined specialty of medicine. It calls for an immaculately designed health-care plan to treat diseases in geriatrics. For chronic illnesses such as diabetes mellitus (DM), coronary heart disease, and hypertension (HTN), they require proper management throughout the rest of patient's life. An integrated treatment pathway helps in treatment decision-making and improving standards of health care for the patient. This case describes an exclusive clinical pharmacist-driven designing of an integrated treatment pathway for a post-coronary artery bypass grafting (CABG) geriatric male patient with DM type I and HTN for the treatment of hypoglycemia and electrolyte imbalance. The treatment begins addressing the chief complaints which were vomiting and unconsciousness. Biochemical screening is essential to establish a diagnosis of electrolyte imbalance along with blood glucose level after which the integrated pathway defines the treatment course. This individualized treatment pathway provides an outline of the course of treatment of acute hypoglycemia, electrolyte imbalance as well as some unconfirmed diagnosis, namely, acute coronary syndrome and respiratory tract infection for a post-CABG geriatric patient with HTN and type 1 DM. The eligibility criterion for patients to be treated according to treatment pathway is to fall in the defined category.

Diabetes and Driving Safety: Science, Ethics, Legality & Practice

Science.gov (United States)

Cox, Daniel J.; Singh, Harsimran; Lorber, Daniel

2013-01-01

Diabetes affects over 25 million people in the United States, most of whom are over the age of 16 and many of whom are licensed to drive a motor vehicle. Safe operation of a motor vehicle requires complex interactions of cognitive and motor functions and medical conditions that affect these functions often will increase the risk of motor vehicle accidents (MVA). In the case of diabetes, hypoglycemia is the most common factor that has been shown to increase MVA rates. When people with diabetes are compared with non-diabetic controls, systematic analyses show that the relative risk of MVA is increased by between 12 and 19% (RRR 1.12-1.19). In comparison, the RRR for Attention Deficit Hyperactivity Disorder is 4.4 and for Sleep Apnea is 2.4. Epidemiologic research suggests that patients at risk for hypoglycemia-related MVAs may have some characteristics in common, including a history of severe hypoglycemia or of hypoglycemia-related driving mishaps. Experimental studies also have shown that people with a history of hypoglycemia-related driving mishaps have abnormal counter-regulatory responses to hypoglycemia and greater cognitive impairments during moderate hypoglycemia. There are medical, ethical and legal issues for health care professionals who care for people with diabetes regarding their patients’ risk of hypoglycemia-related driving mishaps. This includes identifying those at increased risk and counseling them on preventive measures, including more frequent blood glucose testing, delaying driving with low or low normal blood glucose, and carrying readily available emergency supplies in the vehicle for the treatment of hypoglycemia. PMID:23531955

Channelopathies.

Science.gov (United States)

Kim, June-Bum

2014-01-01

Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases.

Change in hexose distribution volume and fractional utilization of [18F]-2-deoxy-2-fluoro-D-glucose in brain during acute hypoglycemia in humans

International Nuclear Information System (INIS)

Shapiro, E.T.; Cooper, M.; Chen, C.T.; Given, B.D.; Polonsky, K.S.

1990-01-01

We used positron emission tomography (PET) to study the effects of mild hypoglycemia on cerebral glucose uptake and metabolism. Nine healthy men were studied under basal saline-infusion conditions, and during euglycemic and hypoglycemic clamp studies. Insulin was infused at the same rate (1 mU.kg-1.min-1) in both clamp studies. In euglycemic clamp studies, glucose was infused at a rate sufficient to maintain the basal plasma glucose concentration, whereas in hypoglycemic clamp studies, the glucose infusion rate was reduced to maintain the plasma glucose at 3.1 mM. Each study lasted 3 h and included a 30-min baseline period and a subsequent 150-min period in which insulin or glucose was administered. Blood samples for measurement of insulin, glucose, cortisol, growth hormone, and glucagon were obtained at 20- to 30-min intervals. A bolus injection of 5-10 mCi [18F]-2-deoxy-2-fluoro-D-glucose (2-DFG) was administered 120 min after initiation of the study, and plasma radioactivity and dynamic PET scans were obtained at frequent intervals for the remaining 40-60 min of the study. Cerebral regions of interest were defined, and concentrations of radioactivity were calculated and used in the three-compartment model of 2-DFG distribution described by Sokoloff. Glucose levels were similar during saline-infusion (4.9 +/- 0.1 mM) and euglycemic clamp (4.8 +/- 0.1 mM) studies, whereas the desired degree of mild hypoglycemia was achieved during the hypoglycemic clamp study (3.1 +/- 0.1 mM, P less than 0.05). The insulin level during saline infusion was 41 +/- 7 pM

Effect of mitochondrial potassium channel on the renal protection mediated by sodium thiosulfate against ethylene glycol induced nephrolithiasis in rat model

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N. Baldev

2015-12-01

Full Text Available Purpose: Sodium thiosulfate (STS is clinically reported to be a promising drug in preventing nephrolithiasis. However, its mechanism of action remains unclear. In the present study, we investigated the role of mitochondrial KATP channel in the renal protection mediated by STS. Materials and Methods: Nephrolithiasis was induced in Wistar rats by administrating 0.4% ethylene glycol (EG along with 1% ammonium chloride for one week in drinking water followed by only 0.75% EG for two weeks. Treatment groups received STS, mitochondrial KATP channel opener and closer exclusively or in combination with STS for two weeks. Results: Animals treated with STS showed normal renal tissue architecture, supported by near normal serum creatinine, urea and ALP activity. Diazoxide (mitochondria KATP channel opening treatment to the animal also showed normal renal tissue histology and improved serum chemistry. However, an opposite result was shown by glibenclamide (mitochondria KATP channel closer treated rats. STS administered along with diazoxide negated the renal protection rendered by diazoxide alone, while it imparted protection to the glibenclamide treated rats, formulating a mitochondria modulated STS action. Conclusion: The present study confirmed that STS render renal protection not only through chelation and antioxidant effect but also by modulating the mitochondrial KATP channel for preventing urolithiasis.

Hindbrain medulla catecholamine cell group involvement in lactate-sensitive hypoglycemia-associated patterns of hypothalamic norepinephrine and epinephrine activity.

Science.gov (United States)

Shrestha, P K; Tamrakar, P; Ibrahim, B A; Briski, K P

2014-10-10

Cell-type compartmentation of glucose metabolism in the brain involves trafficking of the oxidizable glycolytic end product, l-lactate, by astrocytes to fuel neuronal mitochondrial aerobic respiration. Lactate availability within the hindbrain medulla is a monitored function that regulates systemic glucostasis as insulin-induced hypoglycemia (IIH) is exacerbated by lactate repletion of that brain region. A2 noradrenergic neurons are a plausible source of lactoprivic input to the neural gluco-regulatory circuit as caudal fourth ventricular (CV4) lactate infusion normalizes IIH-associated activation, e.g. phosphorylation of the high-sensitivity energy sensor, adenosine 5'-monophosphate-activated protein kinase (AMPK), in these cells. Here, we investigated the hypothesis that A2 neurons are unique among medullary catecholamine cells in directly screening lactate-derived energy. Adult male rats were injected with insulin or vehicle following initiation of continuous l-lactate infusion into the CV4. Two hours after injections, A1, C1, A2, and C2 neurons were collected by laser-microdissection for Western blot analysis of AMPKα1/2 and phosphoAMPKα1/2 proteins. Results show that AMPK is expressed in each cell group, but only a subset, e.g. A1, C1, and A2 neurons, exhibit increased sensor activity in response to IIH. Moreover, hindbrain lactate repletion reversed hypoglycemic augmentation of pAMPKα1/2 content in A2 and C1 but not A1 cells, and normalized hypothalamic norepinephrine and epinephrine content in a site-specific manner. The present evidence for discriminative reactivity of AMPK-expressing medullary catecholamine neurons to the screened energy substrate lactate implies that that lactoprivation is selectively signaled to the hypothalamus by A2 noradrenergic and C1 adrenergic cells. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Hallazgos electroencefalográficos e hipoglucemia severa en niños con diabetes mellitus tipo 1 Electroencephalographic findings and severe hypoglycemia in children with type 1 diabetes mellitus

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Pedro González Fernández

2003-08-01

Full Text Available Los episodios de hipoglucemia severa (HS constituyen un riesgo por ocasionar alteraciones de la función cerebral y del trazado electroencefalográfico (EEG en pacientes con diabetes. El presente estudio tiene como objetivo determinar la frecuencia de alteraciones del EEG después del diagnóstico de diabetes en un grupo de niños y su posible relación con HS, edad, control metabólico y tiempo de evolución de la diabetes. Se estudiaron retrospectivamente 40 niños con edades comprendidas entre 1 y 17 años (media de 12 años con diagnóstico de diabetes mellitus tipo 1 atendidos en el servicio de endocrinología del Hospital Pediátrico Docente "William Soler", en el período comprendido entre abril de 1990 y abril de 1998. Se tomaron los resultados de la hemoglobina glucosilada, así como los episodios referidos de HS. Se realizó EEG al diagnóstico de la diabetes y anualmente. Se clasificaron los EEG anormales de acuerdo con el tipo de trazado. Se encontraron EEG anormales en aproximadamente la mitad de los pacientes (45 % con predominio del trazado con descargas focales, los que fueron significativamente mayor en los pacientes con 2 ó más HS y con una edad menor al diagnóstico de la diabetes. No se encontró relación entre el EEG anormal y el control metabólico ni con el tiempo de evolución de la diabetes. La frecuencia hallada en este estudio enfatiza la importancia de realizar EEG al diagnóstico de DM y posteriormente, sobre todo en aquellos pacientes con HS y edad menor de 6 años.Episodes of severe hypoglycemia (SH constitute a risk because it causes brain function and electroencephalographic recording (EEG disturbances in patients with diabetes. This study was aimed at determining the frequency of EEG alterations after the diagnosis of diabetes in a group of children and their possible relation with SH, age, metabolic control and progression of diabetes. Forty children aged 1 to 17 years (average 12 years diagnosed with type 1

A K ATP channel-dependent pathway within alpha cells regulates glucagon release from both rodent and human islets of Langerhans.

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Patrick E MacDonald

2007-06-01

Full Text Available Glucagon, secreted from pancreatic islet alpha cells, stimulates gluconeogenesis and liver glycogen breakdown. The mechanism regulating glucagon release is debated, and variously attributed to neuronal control, paracrine control by neighbouring beta cells, or to an intrinsic glucose sensing by the alpha cells themselves. We examined hormone secretion and Ca(2+ responses of alpha and beta cells within intact rodent and human islets. Glucose-dependent suppression of glucagon release persisted when paracrine GABA or Zn(2+ signalling was blocked, but was reversed by low concentrations (1-20 muM of the ATP-sensitive K(+ (KATP channel opener diazoxide, which had no effect on insulin release or beta cell responses. This effect was prevented by the KATP channel blocker tolbutamide (100 muM. Higher diazoxide concentrations (>/=30 muM decreased glucagon and insulin secretion, and alpha- and beta-cell Ca(2+ responses, in parallel. In the absence of glucose, tolbutamide at low concentrations (10 muM were inhibitory. In the presence of a maximally inhibitory concentration of tolbutamide (0.5 mM, glucose had no additional suppressive effect. Downstream of the KATP channel, inhibition of voltage-gated Na(+ (TTX and N-type Ca(2+ channels (omega-conotoxin, but not L-type Ca(2+ channels (nifedipine, prevented glucagon secretion. Both the N-type Ca(2+ channels and alpha-cell exocytosis were inactivated at depolarised membrane potentials. Rodent and human glucagon secretion is regulated by an alpha-cell KATP channel-dependent mechanism. We propose that elevated glucose reduces electrical activity and exocytosis via depolarisation-induced inactivation of ion channels involved in action potential firing and secretion.

Blueberry muffin rash, hyperbilirubinemia, and hypoglycemia: a case of hemolytic disease of the fetus and newborn due to anti-Kp(a).

Science.gov (United States)

Brumbaugh, J E; Morgan, S; Beck, J C; Zantek, N; Kearney, S; Bendel, C M; Roberts, K D

2011-05-01

Hemolytic disease of the fetus and newborn occurs when maternal IgG antibodies cross the placenta and cause hemolysis of fetal red blood cells. Kp(a) is a low frequency red blood cell antigen that has rarely been implicated in hemolytic disease of the fetus and newborn. The few reported cases attributed to anti-Kp(a) have typically had minimal clinical consequences. We report a critically ill neonate who presented with purpura, respiratory failure, severe liver dysfunction, hyperbilirubinemia, hypoglycemia and anemia. This case report broadens the spectrum of neonatal disease associated with anti-Kp(a), addresses the evaluation of hemolysis with liver failure in a neonate, and emphasizes the importance of screening for antibodies to low frequency red blood cell antigens in suspected hemolytic disease of the fetus and newborn.

Adaptive Stress Response in Segmental Progeria Resembles Long-Lived Dwarfism and Calorie Restriction in Mice

Science.gov (United States)

Holcomb, Valerie B; von Lindern, Marieke; Jong, Willeke M. C; Zeeuw, Chris I. De; Suh, Yousin; Hasty, Paul; Hoeijmakers, Jan H. J; van der Horst, Gijsbertus T. J; Mitchell, James R

2006-01-01

How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age), including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPDG602D/R722W/XPA−/−) that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80 −/− mouse. Specific (but not all) types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage. PMID:17173483

Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice.

Science.gov (United States)

van de Ven, Marieke; Andressoo, Jaan-Olle; Holcomb, Valerie B; von Lindern, Marieke; Jong, Willeke M C; De Zeeuw, Chris I; Suh, Yousin; Hasty, Paul; Hoeijmakers, Jan H J; van der Horst, Gijsbertus T J; Mitchell, James R

2006-12-15

How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age), including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPD(G602D/R722W)/XPA(-/-)) that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80(-/-) mouse. Specific (but not all) types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage.

Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice.

Directory of Open Access Journals (Sweden)

Marieke van de Ven

2006-12-01

Full Text Available How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age, including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPD(G602D/R722W/XPA(-/- that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80(-/- mouse. Specific (but not all types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage.

Severe hypoglycemia and diabetic ketoacidosis in young persons with preschool onset of type 1 diabetes mellitus: An analysis of three nationwide population-based surveys.

Science.gov (United States)

Lindner, Lena M E; Gontscharuk, Veronika; Bächle, Christina; Castillo, Katty; Stahl-Pehe, Anna; Tönnies, Thaddäus; Yossa, Rhuphine; Holl, Reinhard W; Rosenbauer, Joachim

2018-06-01

To describe incidence rates and temporal trends of severe hypoglycemia (SH) and of hospitalizations for SH or diabetic ketoacidosis (DKA) in persons with early-onset, long-term type 1 diabetes (T1D) and associations of these short-term complications with potential risk factors. This study includes data of 1,875 persons 11.2 to 21.9 years of age with early-onset (10 years) T1D from 3 cross-sectional nationwide, population-based surveys conducted in 2009/2010, 2012/2013 and 2015/2016 using standardized questionnaires. Negative binomial regression was used to estimate incidence rates per 100 person-years (py), temporal trends and associations between potential risk factors and outcomes. The crude incidence rate of SH showed a decreasing trend over time (P for trend = .004), disappearing after adjustment for confounders (P for trend = .341). In contrast, adjusted rates of SH- and DKA-associated hospitalizations did not change significantly between 2009 and 2016 (P for trend = .306 and .774, respectively). Associations between sex, diabetes duration, insulin treatment regimen, hypoglycemia awareness as well as physical activity and SH were found, while family structure was associated with hospitalizations for SH. Family structure, socioeconomic status (SES), diabetes duration, and hemoglobin A1c values showed associations with DKA-related hospitalizations. After adjustment, rates of SH and SH- or DKA-associated hospitalization showed no significant changes in recent years. Structured education programs focusing on high-risk groups as, for example, persons with T1D living with 1 biological parent and the parents' partner or those with a low SES, should be implemented to reduce incidence rates of hospitalizations. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Incidence of severe hypoglycemia in children with type 1 diabetes in the Nordic countries in the period 2008-2012

DEFF Research Database (Denmark)

Birkebaek, N H; Drivvoll, A K; Aakeson, K

2017-01-01

of hemoglobin A1c (HbA1c) and treatment modalities on the frequency of SH; particularly, to explore if a HbA1c target ≤6.7% (50 mmol/mol) is feasible. RESEARCH DESIGN AND METHODS: Data on children below 15 years with a diabetes duration more than 1 year, registered in the national childhood diabetes databases......OBJECTIVE: Treatment of type 1 diabetes has been intensified aiming at normalizing blood glucose, which may increase the risk of severe hypoglycemia (SH). We aimed to compare the incidence of SH events in the four Nordic countries Denmark, Iceland, Norway and Sweden, and to assess the influence...... in the four Nordic countries from 2008 to 2012, were compiled. Data completeness was more than 95%. RESULTS: Totally 8806 (48% females) patients with 29 715 person years were included, mean age and diabetes duration were 11 years and 5.1 years, respectively. The overall rate of SH was 6.0 per 100 patient...

Insulin response of the glucose and fatty acid metabolism in dry dairy cows across a range of body condition scores.

Science.gov (United States)

De Koster, J; Hostens, M; Van Eetvelde, M; Hermans, K; Moerman, S; Bogaert, H; Depreester, E; Van den Broeck, W; Opsomer, G

2015-07-01

The objective of the present research was to determine the insulin response of the glucose and fatty acid metabolism in dry dairy cows with a variable body condition score (BCS). Ten pregnant Holstein Friesian dairy cows (upcoming parity 2 to 5) were selected based on BCS at the beginning of the study (2mo before expected parturition date). During the study, animals were monitored weekly for BCS and backfat thickness and in the last 2wk, blood samples were taken for determination of serum nonesterified fatty acid (NEFA) concentration. Animals underwent a hyperinsulinemic euglycemic clamp test in the third week before the expected parturition date. The hyperinsulinemic euglycemic clamp test consisted of 4 consecutive insulin infusions with increasing insulin doses: 0.1, 0.5, 2, and 5mIU/kg per minute. For each insulin infusion period, a steady state was defined as a period of 30min where no or minor changes of the glucose infusion were necessary to keep the blood glucose concentration constant and near basal levels. During the steady state, the glucose infusion rate [steady state glucose infusion rate (SSGIR) in µmol/kg per minute] and NEFA concentration [steady state NEFA concentration (SSNEFA) in mmol/L] were determined and reflect the insulin response of the glucose and fatty acid metabolism. Dose response curves were created based on the insulin concentrations during the steady state and the SSGIR or SSNEFA. The shape of the dose response curves is determined by the concentration of insulin needed to elicit the half maximal effect (EC50) and the maximal SSGIR or the minimal SSNEFA for the glucose or fatty acid metabolism, respectively. The maximal SSGIR was negatively associated with variables reflecting adiposity of the cows (BCS, backfat thickness, NEFA concentration during the dry period, and absolute weight of the different adipose depots determined after euthanasia and dissection of the different depots), whereas the EC50 of the glucose metabolism was

Vildagliptin as add-on therapy to insulin improves glycemic control without increasing risk of hypoglycemia in Asian, predominantly Chinese, patients with type 2 diabetes mellitus.

Science.gov (United States)

Ning, Guang; Wang, Weiqing; Li, Ling; Ma, Jianhua; Lv, Xiaofeng; Yang, Ming; Wang, Wei; Woloschak, Michael; Lukashevich, Valentina; Kothny, Wolfgang

2016-05-01

The aim of the present study was to investigate the efficacy and safety of vildagliptin added onto insulin with or without metformin in an Asian, predominantly Chinese, population with type 2 diabetes mellitus (T2DM). In this 24-week, multicenter, double-blind, placebo-controlled trial, patients with T2DM inadequately controlled (HbA1c 7.5%-11.0%) on stable therapy with long-acting, intermediate-acting, or premixed insulin, with or without concomitant metformin, were randomized to receive vildagliptin 50 mg b.i.d. or placebo. Of 293 patients randomized, 146 received vildagliptin and 147 received placebo treatment. At baseline, the overall mean age of patients was 58.1 years, mean T2DM duration was 11.3 years, and mean HbA1c was 8.7%. The adjusted mean (±SE) change in HbA1c at Week 24 in the vildagliptin and placebo groups was -1.08 ± 0.12% and -0.38 ± 0.12%, respectively (between-treatment difference -0.70 ± 0.16%; P vildagliptin than with placebo (23.6% vs. 11.2%; P = 0.006). The incidence of adverse events in the vildagliptin and placebo groups was 43.8% and 46.3%, whereas that of serious adverse events was 3.4% and 6.8%, respectively. The frequency of hypoglycemia was lower in the vildagliptin than placebo group (2.7% vs. 5.4%). The addition of vildagliptin 50 mg b.i.d. significantly improved glycemic control without an increased risk of hypoglycemia in Asian, predominantly Chinese, patients with T2DM inadequately controlled on insulin, with or without metformin. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley Sons Australia, & Ltd.

Development of glucose-responsive 'smart' insulin systems.

Science.gov (United States)

Rege, Nischay K; Phillips, Nelson F B; Weiss, Michael A

2017-08-01

The complexity of modern insulin-based therapy for type I and type II diabetes mellitus and the risks associated with excursions in blood-glucose concentration (hyperglycemia and hypoglycemia) have motivated the development of 'smart insulin' technologies (glucose-responsive insulin, GRI). Such analogs or delivery systems are entities that provide insulin activity proportional to the glycemic state of the patient without external monitoring by the patient or healthcare provider. The present review describes the relevant historical background to modern GRI technologies and highlights three distinct approaches: coupling of continuous glucose monitoring (CGM) to deliver devices (algorithm-based 'closed-loop' systems), glucose-responsive polymer encapsulation of insulin, and molecular modification of insulin itself. Recent advances in GRI research utilizing each of the three approaches are illustrated; these include newly developed algorithms for CGM-based insulin delivery systems, glucose-sensitive modifications of existing clinical analogs, newly developed hypoxia-sensitive polymer matrices, and polymer-encapsulated, stem-cell-derived pancreatic β cells. Although GRI technologies have yet to be perfected, the recent advances across several scientific disciplines that are described in this review have provided a path towards their clinical implementation.

Glucose-Lowering Effects and Low Risk of Hypoglycemia in Patients With Maturity-Onset Diabetes of the Young When Treated With a GLP-1 Receptor Agonist

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Ostoft, S. H.; Bagger, J. I.; Hansen, Torben

2014-01-01

OBJECTIVE The most common form of maturity-onset diabetes of the young (MODY), hepatocyte nuclear factor 1 alpha (HNF1A diabetes: MODY3) is often treated with sulfonylureas that confer a high risk of hypoglycemia. We evaluated treatment with GLP-1 receptor agonists (GLP-1RAs) in patients with HNF1A...... diabetes. RESEARCH DESIGN AND METHODS Sixteen patients with HNF1A diabetes (8 women; mean age 39 years [range 23-67 years]; BMI 24.9 +/- 0.5 kg/m(2) [mean +/- SEM]; fasting plasma glucose [FPG] 9.9 +/- 0.9 mmol/L; HbA(1c) 6.4 +/- 0.2% [47 +/- 3 mmol/mol]) received 6 weeks of treatment with a GLP-1RA...

Glycemic control paradox: Poor glycemic control associated with higher one-year and eight-year risks of all-cause hospitalization but lower one-year risk of hypoglycemia in patients with type 2 diabetes.

Science.gov (United States)

Li, Tsai-Chung; Kardia, Sharon L R; Li, Chia-Ing; Chen, Ching-Chu; Liu, Chiu-Shong; Yang, Sing-Yu; Muo, Chin-Shin; Peyser, Patricia A; Lin, Cheng-Chieh

2015-09-01

The relationship between glycemic control and adverse outcomes found in a population with diabetes has seldom been evaluated in patients with type 2 diabetes. We explored the association between hemoglobin A1c (HbA1c) and hospitalization risks within one-year and eight-year follow-up periods. We conducted a retrospective cohort study on 57,061 patients with type 2 diabetes from National Diabetes Case Management Program during 2002-2004 in Taiwan. HbA1c at baseline and in-hospital mortality, all-cause and cause-specific hospitalization over one year and eight years were analyzed. After multivariate adjustment, one-year risk was higher for cases with HbA1c level risk of hypoglycemia hospitalization (0.81, 95% CI: 0.74-0.88). For eight-year risk, subjects with HbA1c level risks of all-cause and diabetes-related hospitalization (1.04, 1.03-1.05, and 1.15, 1.14-1.17, respectively). Higher HbA1c level correlated with lower one-year risk due to hypoglycemia hospitalization but increased one-year and eight-year risks due to all-cause and diabetes-specific hospitalization among Chinese people with type 2 diabetes in Taiwan. Future study must ascertain how to meet HbA1c targets and improve outcome without risk to this population. Copyright © 2015 Elsevier Inc. All rights reserved.

Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth.

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Stacy Zamudio

2010-01-01

Full Text Available The most well known reproductive consequence of residence at high altitude (HA >2700 m is reduction in fetal growth. Reduced fetoplacental oxygenation is an underlying cause of pregnancy pathologies, including intrauterine growth restriction and preeclampsia, which are more common at HA. Therefore, altitude is a natural experimental model to study the etiology of pregnancy pathophysiologies. We have shown that the proximate cause of decreased fetal growth is not reduced oxygen availability, delivery, or consumption. We therefore asked whether glucose, the primary substrate for fetal growth, might be decreased and/or whether altered fetoplacental glucose metabolism might account for reduced fetal growth at HA.Doppler and ultrasound were used to measure maternal uterine and fetal umbilical blood flows in 69 and 58 residents of 400 vs 3600 m. Arterial and venous blood samples from mother and fetus were collected at elective cesarean delivery and analyzed for glucose, lactate and insulin. Maternal delivery and fetal uptakes for oxygen and glucose were calculated.The maternal arterial - venous glucose concentration difference was greater at HA. However, umbilical venous and arterial glucose concentrations were markedly decreased, resulting in lower glucose delivery at 3600 m. Fetal glucose consumption was reduced by >28%, but strongly correlated with glucose delivery, highlighting the relevance of glucose concentration to fetal uptake. At altitude, fetal lactate levels were increased, insulin concentrations decreased, and the expression of GLUT1 glucose transporter protein in the placental basal membrane was reduced.Our results support that preferential anaerobic consumption of glucose by the placenta at high altitude spares oxygen for fetal use, but limits glucose availability for fetal growth. Thus reduced fetal growth at high altitude is associated with fetal hypoglycemia, hypoinsulinemia and a trend towards lactacidemia. Our data support that

Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass

DEFF Research Database (Denmark)

Myint, K S; Greenfield, J R; Farooqi, I S

2012-01-01

Spontaneous hyperinsulinaemic hypoglycaemia following gastric bypass surgery (GBS) is increasingly recognised. However, its pathophysiology remains unclear. Some patients require pancreatectomy. Medical therapy with calcium channel blockers, acarbose and diazoxide has been reported to be beneficial...

Cost-effectiveness analysis of sensor-augmented pump therapy with low glucose-suspend in patients with type 1 diabetes mellitus and high risk of hypoglycemia in Spain.

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Conget, Ignacio; Martín-Vaquero, Pilar; Roze, Stéphane; Elías, Isabel; Pineda, Cristina; Álvarez, María; Delbaere, Alexis; Ampudia-Blasco, Francisco Javier

2018-05-19

To compare the cost-effectiveness of sensor-augmented pump therapy (SAP) [continuous subcutaneous insulin infusion (CSII) plus real-time continuous glucose monitoring (RT-CGM)] with low glucose suspend (MiniMed™ Veo™) and CSII alone in patients with type 1 diabetes mellitus (T1DM) at high risk of hypoglycemia in Spain. The IQVIA CORE Diabetes Model was used to estimate healthcare outcomes as life-years gained (LYGs) and quality-adjusted life years (QALYs), and to project lifetime costs. Information about efficacy, resource utilization, and unit costs (€2016) was taken from published sources and validated by an expert panel. Analyses were performed from both the Spanish National Health System (NHS) perspective and the societal perspective. From the NHS perspective, SAP with low glucose suspend was associated to a €47,665 increase in direct healthcare costs and to increases of 0.19 LYGs and 1.88 QALYs, both discounted, which resulted in an incremental cost-effectiveness ratio (ICER) of €25,394/QALY. From the societal perspective, SAP with low glucose suspend increased total costs (including direct and indirect healthcare costs) by €41,036, with a resultant ICER of €21,862/QALY. Considering the willingness-to-pay threshold of €30,000/QALY in Spain, SAP with low glucose suspend represents a cost-effective option from both the NHS and societal perspectives. Sensitivity analyses confirmed the robustness of the model. From both the Spanish NHS perspective and the societal perspective, SAP with low glucose suspend is a cost-effective option for the treatment of T1DM patients at high risk of hypoglycemia. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Predictive value of glucose-insulin ratio in PCOS and profile of women who will benefit from metformin therapy: obese, lean, hyper or normoinsulinemic?

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Onalan, Gogsen; Goktolga, Umit; Ceyhan, Temel; Bagis, Tayfun; Onalan, Reside; Pabuçcu, Recai

2005-12-01

The aim of the present study is to evaluate sub-groups of PCOS patients who will benefit from metformin therapy and to find out any predictors of ovulation in PCOS sub-groups. In the current prospective-randomized, placebo-controlled, double-blind study, PCOS patients (n = 116) were divided into six main groups according to glucose to insulin ratio (G-I ratio mg/10(-4) U) and body mass index (BMI kg/m2) as: Group 1: normoinsulinemic (G-I ratio > or = 4.5 mg/10(-4) U), lean (BMI or = 30) (n = 18); Group 4: hyperinsulinemic (G-I ratio lean (n = 28); Group 5: hyperinsulinemic, overweight (n = 17); Group 6: hyperinsulinemic, obese (n = 20). Patients in each group were randomized onto placebo or metformin treatments (850 mg two to three times per day according to BMI). The rate of ovulation, biochemical profile, hormonal profile and clinical symptoms of hyperandrogenism were evaluated before and after 6 months of metformin and placebo treatments. We observed a significant decrease in WHR following metformin therapy in the normoinsulinemic overweight sub-group (P lean women (P lean hyperinsulinemic and normoinsulinemic groups (P lean hyperinsulinemic women (P PCOS patients.

Isoattenuating insulinomas at biphasic contrast-enhanced CT: frequency, clinicopathologic features and perfusion characteristics

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Zhu, Liang; Xue, Hua-dan; Sun, Hao; Wang, Xuan; He, Yong-lan; Jin, Zheng-yu [Peking Union Medical College Hospital, Department of Radiology, Beijing (China); Zhao, Yu-pei [Peking Union Medical College Hospital, Department of General Surgery, Beijing (China)

2016-10-15

We aimed to determine the frequency of isoattenuating insulinomas, to investigate their clinicopathological features and to assess their regional pancreatic perfusion characteristics. Institutional review board approval was obtained, and patient informed consent was waived. From July 2010 to June 2014, 170 patients (66 male, 104 female) with endogenous hyperinsulinemic hypoglycemia underwent biphasic contrast-enhanced CT before surgery, and 129 of those patients also received preoperative whole-pancreas CT perfusion. A total of 181 tumours were proved histopathologically after surgery. Enhancement pattern and regional pancreatic perfusion characteristics were analyzed. Clinical features, tumour size and pathological grading were investigated. The frequency of isoattenuating tumours was 24.9 %. Tumour size and WHO grading was not significantly different between isoattenuating and hyperattenuating tumours. Tumour-free regions had identical blood flow (BF) regardless of their location (p = 0.35). Isoattenuating tumour-harbouring regions had lower BF compared with hyperattenuating tumour-harbouring regions; both showed higher BF compared with tumour-free neighbourhood regions (all p < 0.01). For patients with isoattenuating tumours, the overall hospital stay was longer (p < 0.01). A substantial subset of insulinomas were isoattenuating on biphasic CT. CT perfusion showed higher BF in tumour-harbouring regions compared to tumour-free regions, providing a clue for tumour regionalization. (orig.)

Localization of Hidden Insulinomas with ⁶⁸Ga-DOTA-Exendin-4 PET/CT: A Pilot Study.

Science.gov (United States)

Antwi, Kwadwo; Fani, Melpomeni; Nicolas, Guillaume; Rottenburger, Christof; Heye, Tobias; Reubi, Jean Claude; Gloor, Beat; Christ, Emanuel; Wild, Damian

2015-07-01

(111)In-DOTA-exendin-4 SPECT/CT has been shown to be highly efficient in the detection of insulinomas. We aimed at determining whether novel PET/CT imaging with [Nle(14),Lys(40)(Ahx-DOTA-(68)Ga)NH2]exendin-4 ((68)Ga-DOTA-exendin-4) is feasible and sensitive in detecting benign insulinomas. (68)Ga-DOTA-exendin-4 PET/CT and (111)In-DOTA-exendin-4 SPECT/CT were performed in a randomized cross-over order on 5 patients with endogenous hyperinsulinemic hypoglycemia. The gold standard for comparison was the histologic diagnosis after surgery. In 4 patients histologic diagnosis confirmed a benign insulinoma, whereas one patient refused surgery despite a positive (68)Ga-DOTA-exendin-4 PET/CT scan. In 4 of 5 patients, previously performed conventional imaging (CT or MR imaging) was not able to localize the insulinoma. (68)Ga-DOTA-exendin-4 PET/CT correctly identified the insulinoma in 4 of 4 patients, whereas (111)In-DOTA-exendin-4 SPECT/CT correctly identified the insulinoma in only 2 of 4 patients. These preliminary data suggest that the use of (68)Ga-DOTA-exendin-4 PET/CT in detecting hidden insulinomas is feasible. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

[Effects of coca chewing on the glucose tolerance test].

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Galarza Guzmán, M; Peñaloza Imaña, R; Echalar Afcha, L; Aguilar Valerio, M; Spielvogel, H; Sauvain, M

1997-01-01

The effects of coca chewing on the glucose tolerance test were measured. The subjects were 14 habitual coca chewers and 14 non-chewers. All were of Aymara ancestry and came from a rural community from the "Altiplano" close to the city of La Paz. The coca users chewed coca leaves during 3 1/2 hours of the test. The non-chewers showed a significant hypoglycemia at 120 minutes of the test. This effect was not observed in the coca chewers. The hormonal counter-regulation response to hypoglycemia worked perfectly in non-chewers, since glucose levels reached normal values at 180 minutes of the test. These results suggest that coca chewers, at high altitude do not present hypoglycemia, due to an antagonic action of coca metabolites on insulin; allowing a greater availability of glucose in the organism. This would have a positive effect on metabolism in an environment of hypobaric hypoxia, known to lead to situations of hypoglycemia.

Role of opioid tone in the pathophysiology of hyperinsulinemia and insulin resistance in polycystic ovarian disease.

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Fulghesu, A M; Ciampelli, M; Guido, M; Murgia, F; Caruso, A; Mancuso, S; Lanzone, A

1998-02-01

Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of polycystic ovarian disease (PCOD). On the other hand, being generally admitted that opioids may play a role in glycoregulation and that opioid tone is altered in PCOD, an involvement of the opioids in determining the hyperinsulinemia of PCOD patients could be suggested. The aim of this study was to evaluate the effect of a chronic opioid blockade on insulin metabolism and peripheral insulin sensitivity in PCOD hyperinsulinemic patients. Twenty-three women with PCOD were studied. An oral glucose tolerance test (OGTT) and a clamp study were performed at baseline (during the follicular phase) and after 6 weeks of naltrexone administration (50 mg/d orally). Based on the insulinemic response to the OGTT, 16 women were classified as hyperinsulinemic and seven as normoinsulinemic. Naltrexone treatment significantly reduced fasting (P PCOD patients.

Local and systemic response to intramammary lipopolysaccharide challenge during long-term manipulated plasma glucose and insulin concentrations in dairy cows.

Science.gov (United States)

Vernay, M C M B; Wellnitz, O; Kreipe, L; van Dorland, H A; Bruckmaier, R M

2012-05-01

The metabolic load during periods of high milk production in dairy cows causes a variety of changes of metabolite blood concentrations including dramatically decreased glucose levels. These changes supposedly impair the immune system. The goal of this study was, therefore, to evaluate adaptations of the cow's immune system in response to an intramammary lipopolysaccharide (LPS) stimulation during a 3-d modification of plasma glucose and insulin induced by different clamp infusions. Seventeen midlactating dairy cows received a hypoglycemic hyperinsulinemic clamp induced by insulin infusion (HypoG; n=5), a euglycemic hyperinsulinemic clamp induced by insulin and glucose infusion (EuG; n=6), or infusion of saline solution (NaCl; n=6) for 56 h. At 48 h of infusion, 2 udder quarters were challenged with 200 μg of Escherichia coli LPS. At 48 h of infusion (immediately before LPS challenge), tumor necrosis factor α, lactoferrin, and serum amyloid A (SAA) mRNA abundance was increased in HypoG and Il-1β mRNA abundance was decreased in EuG. After LPS challenge, plasma glucose concentration did not decrease, although plasma insulin increased simultaneously in all groups either due to enhanced endogenous release (NaCl) or due to increased insulin infusion rate (HypoG; EuG). Plasma cortisol, rectal temperatures, and milk somatic cell count of challenged quarters increased, whereas plasma nonesterified fatty acid concentrations were similarly decreased across treatments. In mammary biopsies, increased mRNA expression of tumor necrosis factor α, IL-1β, IL-8, and IL-10, and SAA were observed in LPS-treated quarters of all groups, with a more pronounced increase in IL-1β, IL-10, and SAA expression in EuG. Nuclear factor-κB mRNA expression was upregulated in NaCl and EuG but not in HypoG in response to LPS. Lactoferrin, toll-like receptor 4, and cyclooxygenase-2 mRNA expression was increased in LPS-treated quarters of EuG only, and 5-lipoxygenase mRNA expression was decreased

Conjoint regulation of glucagon concentrations via plasma insulin and glucose in dairy cows.

Science.gov (United States)

Zarrin, M; Wellnitz, O; Bruckmaier, R M

2015-04-01

Insulin and glucagon are glucoregulatory hormones that contribute to glucose homeostasis. Plasma insulin is elevated during normoglycemia or hyperglycemia and acts as a suppressor of glucagon secretion. We have investigated if and how insulin and glucose contribute to the regulation of glucagon secretion through long term (48 h) elevated insulin concentrations during simultaneous hypoglycemia or euglycemia in mid-lactating dairy cows. Nineteen Holstein dairy cows were randomly assigned to 3 treatment groups: an intravenous insulin infusion (HypoG, n = 5) to decrease plasma glucose concentrations (2.5 mmol/L), a hyperinsulinemic-euglycemic clamp to study effects of insulin at simultaneously normal glucose concentrations (EuG, n = 6) and a 0.9% saline infusion (NaCl, n = 8). Plasma glucose was measured at 5-min intervals, and insulin and glucose infusion rates were adjusted accordingly. Area under the curve of hourly glucose, insulin, and glucagon concentrations on day 2 of infusion was evaluated by analysis of variance with treatments as fixed effect. Insulin infusion caused an increase of plasma insulin area under the curve (AUC)/h in HypoG (41.9 ± 8.1 mU/L) and EuG (57.8 ± 7.8 mU/L) compared with NaCl (13.9 ± 1.1 mU/L; P insulin infusion induces elevated glucagon concentrations during hypoglycemia, although the same insulin infusion reduces glucagon concentrations at simultaneously normal glucose concentrations. Thus, insulin does not generally have an inhibitory effect on glucagon concentrations. If simultaneously glucose is low and insulin is high, glucagon is upregulated to increase glucose availability. Therefore, insulin and glucose are conjoint regulatory factors of glucagon concentrations in dairy cows, and the plasma glucose status is the key factor to decide if its concentrations are increased or decreased. This regulatory effect can be important for the maintenance of glucose homeostasis if insulin secretion is upregulated by other factors than high

Evaluating the clinical accuracy of two continuous glucose sensors using continuous glucose-error grid analysis.

Science.gov (United States)

Clarke, William L; Anderson, Stacey; Farhy, Leon; Breton, Marc; Gonder-Frederick, Linda; Cox, Daniel; Kovatchev, Boris

2005-10-01

To compare the clinical accuracy of two different continuous glucose sensors (CGS) during euglycemia and hypoglycemia using continuous glucose-error grid analysis (CG-EGA). FreeStyle Navigator (Abbott Laboratories, Alameda, CA) and MiniMed CGMS (Medtronic, Northridge, CA) CGSs were applied to the abdomens of 16 type 1 diabetic subjects (age 42 +/- 3 years) 12 h before the initiation of the study. Each system was calibrated according to the manufacturer's recommendations. Each subject underwent a hyperinsulinemic-euglycemic clamp (blood glucose goal 110 mg/dl) for 70-210 min followed by a 1-mg.dl(-1).min(-1) controlled reduction in blood glucose toward a nadir of 40 mg/dl. Arterialized blood glucose was determined every 5 min using a Beckman Glucose Analyzer (Fullerton, CA). CGS glucose recordings were matched to the reference blood glucose with 30-s precision, and rates of glucose change were calculated for 5-min intervals. CG-EGA was used to quantify the clinical accuracy of both systems by estimating combined point and rate accuracy of each system in the euglycemic (70-180 mg/dl) and hypoglycemic (<70 mg/dl) ranges. A total of 1,104 data pairs were recorded in the euglycemic range and 250 data pairs in the hypoglycemic range. Overall correlation between CGS and reference glucose was similar for both systems (Navigator, r = 0.84; CGMS, r = 0.79, NS). During euglycemia, both CGS systems had similar clinical accuracy (Navigator zones A + B, 88.8%; CGMS zones A + B, 89.3%, NS). However, during hypoglycemia, the Navigator was significantly more clinically accurate than the CGMS (zones A + B = 82.4 vs. 61.6%, Navigator and CGMS, respectively, P < 0.0005). CG-EGA is a helpful tool for evaluating and comparing the clinical accuracy of CGS systems in different blood glucose ranges. CG-EGA provides accuracy details beyond other methods of evaluation, including correlational analysis and the original EGA.

Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism

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Wanchun Yang

2014-01-01

Full Text Available Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR, a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1 activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1 as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals.

Simulation and qualitative analysis of glucose variability, mean glucose, and hypoglycemia after subcutaneous insulin therapy for stress hyperglycemia.

Science.gov (United States)

Strilka, Richard J; Stull, Mamie C; Clemens, Michael S; McCaver, Stewart C; Armen, Scott B

2016-01-27

The critically ill can have persistent dysglycemia during the "subacute" recovery phase of their illness because of altered gene expression; it is also not uncommon for these patients to receive continuous enteral nutrition during this time. The optimal short-acting subcutaneous insulin therapy that should be used in this clinical scenario, however, is unknown. Our aim was to conduct a qualitative numerical study of the glucose-insulin dynamics within this patient population to answer the above question. This analysis may help clinicians design a relevant clinical trial. Eight virtual patients with stress hyperglycemia were simulated by means of a mathematical model. Each virtual patient had a different combination of insulin resistance and insulin deficiency that defined their unique stress hyperglycemia state; the rate of gluconeogenesis was also doubled. The patients received 25 injections of subcutaneous regular or Lispro insulin (0-6 U) with 3 rates of continuous nutrition. The main outcome measurements were the change in mean glucose concentration, the change in glucose variability, and hypoglycemic episodes. These end points were interpreted by how the ultradian oscillations of glucose concentration were affected by each insulin preparation. Subcutaneous regular insulin lowered both mean glucose concentrations and glucose variability in a linear fashion. No hypoglycemic episodes were noted. Although subcutaneous Lispro insulin lowered mean glucose concentrations, glucose variability increased in a nonlinear fashion. In patients with high insulin resistance and nutrition at goal, "rebound hyperglycemia" was noted after the insulin analog was rapidly metabolized. When the nutritional source was removed, hypoglycemia tended to occur at higher Lispro insulin doses. Finally, patients with severe insulin resistance seemed the most sensitive to insulin concentration changes. Subcutaneous regular insulin consistently lowered mean glucose concentrations and glucose

Relationship between serum adiponectin concentration, body condition score, and peripheral tissue insulin response of dairy cows during the dry period.

Science.gov (United States)

De Koster, J; Urh, C; Hostens, M; Van den Broeck, W; Sauerwein, H; Opsomer, G

2017-04-01

The aim of the present study was to describe the relationship between serum adiponectin concentration and peripheral tissue insulin response in dairy cows with a variable body condition score (BCS) during the dry period. Cows were selected at the beginning of the dry period based on BCS (BCS 3.75, n = 5). Animals were followed from the beginning of the dry period by weekly blood sampling and assessment of BCS and backfat thickness. Weekly blood samples were analyzed for adiponectin concentration using a bovine specific ELISA. Hyperinsulinemic euglycemic clamp tests were performed at the end of the dry period to measure peripheral tissue insulin response. Insulin dose response curves were established for both glucose and fatty acid metabolism. Regression analysis revealed that the serum concentrations of adiponectin dropped at the end of the dry period (P insulin responsiveness (reflecting the maximal effect of insulin; r = 0.76, P insulin sensitivity (reflecting the insulin concentration needed to achieve halfmaximal effect; r = -0.54, P = 0.13). At the level of the fatty acid metabolism, greater adiponectin concentrations were negatively correlated with lower NEFA levels during the HEC test reflecting the insulin responsiveness of the NEFA metabolism (r = -0.61, P = 0.08), whereas there was no association with the insulin sensitivity of the NEFA metabolism (r = -0.16, P = 0.67). In conclusion, serum concentrations of adiponectin were negatively associated with the BCS of dairy cows during the dry period and positively associated with insulin responsiveness of the glucose and fatty acid metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypoglycemia hospitalization frequency in patients with type 2 diabetes mellitus: a comparison of dipeptidyl peptidase 4 inhibitors and insulin secretagogues using the French health insurance database

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Detournay B

2015-07-01

Full Text Available Bruno Detournay,1 Serge Halimi,2,3 Julien Robert,1 Céline Deschaseaux,4 Sylvie Dejager5,6 1Cemka-Eval, Bourg-la Reine, France; 2Department of Diabetology, Endocrinology and Nutrition, Grenoble University Hospital Center, Grenoble, France; 3University Joseph Fourier, Grenoble, France; 4Novartis Pharma SAS, Market Access Department, Rueil-Malmaison, France; 5Novartis Pharma SAS, Medical and Scientific Affairs, Rueil Malmaison, France; 6Department of Diabetology, Metabolism and Endocrinology, Pitié-Salpétrière Hospital, Paris, France Aim: We aimed to compare the frequency of severe hypoglycemia leading to hospitalization (HH and emergency visits (EV for any cause in patients with type 2 diabetes mellitus exposed to dipeptidyl peptidase 4 (DPP4 inhibitors (DPP4-i versus those exposed to insulin secretagogues (IS; sulfonylureas or glinides. Methods: Data were extracted from the EGB (Echantillon Généraliste des Bénéficiaires database, comprising a representative sample of ~1% of patients registered in the French National Health Insurance System (~600,000 patients. Type 2 diabetes mellitus patients exposed to regimens containing either a DPP4-i (excluding treatment with IS, insulin, or glucagon-like peptide 1 analog or IS (excluding treatment with insulin and any incretin therapy between 2009 and 2012 were selected. HH and EV during the exposure periods were identified in both cohorts. A similar analysis was conducted considering vildagliptin alone versus IS. Comparative analyses adjusting for covariates within the model (subjects matched for key characteristics and using multinomial regression models were performed. Results: Overall, 7,152 patients exposed to any DPP4-i and 1,440 patients exposed to vildagliptin were compared to 10,019 patients exposed to IS. Eight patients (0.11% from the DPP4-i cohort and none from the vildagliptin cohort (0.0% were hospitalized for hypoglycemia versus 130 patients (1.30% from the IS cohort (138

Blood pressure regulation in diabetic autonomic neuropathy

DEFF Research Database (Denmark)

Hilsted, J

1985-01-01

Defective blood pressure responses to standing, exercise and epinephrine infusions have been demonstrated in diabetic patients with autonomic neuropathy. The circulatory mechanisms underlying blood pressure responses to exercise and standing up in these patients are well characterized: In both...... which may contribute to exercise hypotension in these patients. During hypoglycemia, blood pressure regulation seems intact in patients with autonomic neuropathy. This is probably due to release of substantial amounts of catecholamines during these experiments. During epinephrine infusions a substantial...... blood pressure fall ensues in patients with autonomic neuropathy, probably due to excessive muscular vasodilation. It is unresolved why blood pressure regulation is intact during hypoglycemia and severely impaired--at similar catecholamine concentrations--during epinephrine infusions....

The Effect of Diazoxide Upon Heat Shock Protein and Physiological Response to Hemorrhagic Shock and Cerebral Stroke

Science.gov (United States)

2006-06-16

requirements. Buprenex ( Reckitt Benckiser Pharm, Richmond, VA) was given subcutaneously for post-surgical discomfort. For euthanization, the rats 67...areas to reduce anesthetic requirements. Buprenex ( Reckitt Benckiser Pharm, Richmond, VA) was given subcutaneously (0.03 mg/kg) for post-surgical

Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.

Science.gov (United States)

Vinik, A I; Seino, S; Funakoshi, A; Schwartz, J; Matsumoto, M; Schteingart, D E; Fu, Z Z; Tsai, S T

1986-04-01

A 45-yr-old muscular nonobese white man who had a 9-yr history of syncopal episodes was studied on several occasions between April 1979 and August 1984. Fasting glucose concentrations ranged between 74-115 mg/dl, and those of insulin ranged between 14-64 microU/ml. Reactive hypoglycemia 3-4 h after ingestion of glucose occurred in the first 2 yr. Glucose tolerance was impaired in 1979, from February 1982 through September 1983, and again in August 1984. The maximum plasma insulin response to glucose ranged between 475-1630 microU/ml. When studied in November 1982, insulin (0.1 U/kg) caused a fall in blood glucose concentration of only 25% (normal, greater than 50%), and maximal glucose utilization during the euglycemic hyperinsulinemic clamp was 7.5 mg/kg . min (normal, greater than 12 mg/kg . min). Plasma counterregulatory hormone concentrations were normal, and antibodies to insulin and the insulin receptor were absent. Binding of exogenous insulin to the patient's cellular receptors (monocytes, red blood cells, and skin fibroblasts) was normal. Insulin was purified from plasma by immunoaffinity and molecular sieve chromatography and was found to elute later than human insulin on reversed phase high performance liquid chromatography. It was more hydrophobic than normal human insulin and had only 10% of the activity of normal insulin in terms of ability to bind to and stimulate glucose metabolism in isolated rat adipocytes. The abnormal insulin was identified in two of three sons and a sister, but not in the mother, brother, or niece. Sensitivity to insulin was normal in the two sons who had abnormal insulin. These results suggest that in this family the abnormal insulin was due to a biosynthetic defect, inherited as an autosomal dominant trait. The hyperinsulinemia was not associated with diabetes in family members who had no insulin resistance.

Moringa Oleifera leaf extract increases plasma antioxidant status associated with reduced plasma malondialdehyde concentration without hypoglycemia in fasting healthy volunteers.

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Ngamukote, Sathaporn; Khannongpho, Teerawat; Siriwatanapaiboon, Marent; Sirikwanpong, Sukrit; Dahlan, Winai; Adisakwattana, Sirichai

2016-12-29

To investigate the effect of Moringa Oleifera leaf extract (MOLE) on plasma glucose concentration and antioxidant status in healthy volunteers. A randomized crossover design was used in this study. Healthy volunteers were randomly assigned to receive either 200 mL of warm water (10 cases) or 200 mL of MOLE (500 mg dried extract, 10 cases). Blood samples were drawn at 0, 30, 60, 90, and 120 min for measuring fasting plasma glucose (FPG), ferric reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC) and malondialdehyde (MDA). FPG concentration was not signifificantly different between warm water and MOLE. The consumption of MOLE acutely improved both FRAP and TEAC, with increases after 30 min of 30 μmol/L FeSO 4 equivalents and 0.18 μmol/L Trolox equivalents, respectively. The change in MDA level from baseline was signifificantly lowered after the ingestion of MOLE at 30, 60, and 90 min. In addition, FRAP level was negatively correlated with plasma MDA level after an intake of MOLE. MOLE increased plasma antioxidant capacity without hypoglycemia in human. The consumption of MOLE may reduce the risk factors associated with chronic degenerative diseases.

Energetic stress: The reciprocal relationship between energy availability and the stress response.

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Harrell, C S; Gillespie, C F; Neigh, G N

2016-11-01

The worldwide epidemic of metabolic syndromes and the recognized burden of mental health disorders have driven increased research into the relationship between the two. A maladaptive stress response is implicated in both mental health disorders and metabolic disorders, implicating the hypothalamic-pituitary-adrenal (HPA) axis as a key mediator of this relationship. This review explores how an altered energetic state, such as hyper- or hypoglycemia, as may be manifested in obesity or diabetes, affects the stress response and the HPA axis in particular. We propose that changes in energetic state or energetic demands can result in "energetic stress" that can, if prolonged, lead to a dysfunctional stress response. In this review, we summarize the role of the hypothalamus in modulating energy homeostasis and then briefly discuss the relationship between metabolism and stress-induced activation of the HPA axis. Next, we examine seven mechanisms whereby energetic stress interacts with neuroendocrine stress response systems, including by glucocorticoid signaling both within and beyond the HPA axis; by nutrient-induced changes in glucocorticoid signaling; by impacting the sympathetic nervous system; through changes in other neuroendocrine factors; by inducing inflammatory changes; and by altering the gut-brain axis. Recognizing these effects of energetic stress can drive novel therapies and prevention strategies for mental health disorders, including dietary intervention, probiotics, and even fecal transplant. Copyright © 2015 Elsevier Inc. All rights reserved.

Stressor specificity of central neuroendocrine responses: implications for stress-related disorders.

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Pacák, K; Palkovits, M

2001-08-01

Despite the fact that many research articles have been written about stress and stress-related diseases, no scientifically accepted definition of stress exists. Selye introduced and popularized stress as a medical and scientific idea. He did not deny the existence of stressor-specific response patterns; however, he emphasized that such responses did not constitute stress, only the shared nonspecific component. In this review we focus mainly on the similarities and differences between the neuroendocrine responses (especially the sympathoadrenal and the sympathoneuronal systems and the hypothalamo-pituitary-adrenocortical axis) among various stressors and a strategy for testing Selye's doctrine of nonspecificity. In our experiments, we used five different stressors: immobilization, hemorrhage, cold exposure, pain, or hypoglycemia. With the exception of immobilization stress, these stressors also differed in their intensities. Our results showed marked heterogeneity of neuroendocrine responses to various stressors and that each stressor has a neurochemical "signature." By examining changes of Fos immunoreactivity in various brain regions upon exposure to different stressors, we also attempted to map central stressor-specific neuroendocrine pathways. We believe the existence of stressor-specific pathways and circuits is a clear step forward in the study of the pathogenesis of stress-related disorders and their proper treatment. Finally, we define stress as a state of threatened homeostasis (physical or perceived treat to homeostasis). During stress, an adaptive compensatory specific response of the organism is activated to sustain homeostasis. The adaptive response reflects the activation of specific central circuits and is genetically and constitutionally programmed and constantly modulated by environmental factors.

An Atypical HNF4A Mutation Which Does Not Conform to the Classic Presentation of HNF4A-MODY

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Andrew J. Spiro

2018-01-01

Full Text Available Objective. To present the case of an atypical Hepatocyte Nuclear Factor 4 Alpha (HNF4A mutation that is not consistent with the classically published presentation of HNF4A-Mature Onset Diabetes of the Young (MODY. Methods. Clinical presentation and literature review. Results. A 43-year-old nonobese man was referred to the endocrinology clinic for evaluation of elevated fasting blood glucose (FBG measurements. Laboratory review revealed prediabetes and hypertriglyceridemia for the previous decade. Testing of autoantibodies for type 1 diabetes was negative. Genetic testing showed an autosomal dominant, heterozygous missense mutation (c.991C>T; p.Arg331Cys in the HNF4A gene, which is correlated with HNF4A-MODY. Phenotypically, patients with an HNF4A-MODY tend to have early-onset diabetes, microvascular complications, low triglyceride levels, increased birth weight, fetal macrosomia, and less commonly neonatal hyperinsulinemic hypoglycemia. The patient did not demonstrate any of these features but instead presented with late-onset diabetes, an elevated triglyceride level, and a normal birth weight. Conclusion. Our patient likely represents an atypical variant of HNF4A-MODY with a milder clinical presentation. Patients with atypical, less-severe presentations of HNF4A-MODY may be largely undiagnosed or misdiagnosed, but identification is important due to implications for treatment, pregnancy, and screening of family members.

Hepatic Glucose Production Increases in Response to Metformin Treatment in the Glycogen-depleted State

DEFF Research Database (Denmark)

Christensen, Mette Marie Hougaard; Højlund, Kurt; Hother-Nielsen, Ole

with two reduced-function alleles) were fasted for 42 h twice. In one of the periods, before the fasting, the volunteers were titrated to steady-state with 1 g metformin twice daily for seven days. Parameters of whole-body glucose metabolism were assessed using [3-3^H] glucose, indirect calorimetry......Metformin is believed to reduce glucose levels primarily by inhibiting hepatic glucose production, but at the same time do not cause hypoglycemia. Recent data indicate that metformin antagonizes the major glucose counterregulatory hormone, glucagon suggesting that other mechanisms protect against...... hypoglycemia. Here, we examined the effect of metformin on whole-body glucose metabolism after a glycogen-depleting 40 h fast and the role of reduced-function alleles in OCT1. In a randomized cross-over trial, 34 healthy volunteers with known OCT1 genotypes (12 with two wild-type alleles, 13 with one and 9...

Effect of antrectomy on the nervous phase of gastric secretion in the dog.

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Caboclo, J L; Wolfe, M M; Hocking, M P; McGuigan, J E; Woodward, E R

1981-09-01

A method is described for complete isolation of the stomach in the dog with vagal innervation intact. This involves esophagostomy, double mucosal closure of the pylorus and a Maydl gastric fistula combined with gastrojejunostomy. The latter is occluded during periods of study. In this preparation the responses to sham feeding and to insulin-induced hypoglycemia were reduced approximately 10-fold, reiterating the significant synergistic effect of gastrin on vagal stimulation of the parietal cell mass. However, significant acid secretion could still be induced in this preparation by both sham feeding and insulin-induced hypoglycemia.

High-dose fasudil preserves postconditioning against myocardial infarction under hyperglycemia in rats: role of mitochondrial KATP channels

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Ichinomiya Taiga

2012-03-01

Full Text Available Abstract Background The current study was carried out to determine whether fasudil hydrochloride (fasudil, a Rho-kinase inhibitor, has myocardial postconditioning (PostC activity under hyperglycemia as well as normoglycemia, and if so, whether the effects could be mediated by mitochondrial ATP-sensitive potassium (m-KATP channels. Methods Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. After opening the chest, all rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received low-dose (0.15 mg/kg or high-dose (0.5 mg/kg fasudil or diazoxide, an m-KATP channel opener, at 10 mg/kg, just before reperfusion under normoglycemic or hyperglycemic conditions. In another group, rats received 5-hydroxydecanoic acid (5HD, an m-KATP channel blocker, at 10 mg/kg, before high-dose fasudil. Myocardial infarct size was expressed as a percentage of area at risk (AAR. Results Under normoglycemia, low-dose and high-dose fasudil and diazoxide reduced myocardial infarct size (23 ± 8%, 21 ± 9% and 21 ± 10% of AAR, respectively compared with that in the control (42 ± 7%. Under hyperglycemia, low-dose fasudil (40 ± 11% and diazoxide (44 ± 14% could not exert this beneficial effect, but high-dose fasudil reduced myocardial infarct size in the same manner as under normoglycemia (21 ± 13%. 5HD prevented fasudil-induced reduction of myocardial infarct size (42 ± 13%. Conclusion Fasudil induces PostC against myocardial infarction via activation of m-KATP channels in the rat. Although hyperglycemia attenuates the PostC, high-dose fasudil can restore cardioprotection.

Obligatory Role of Intraluminal O2− in Acute Endothelin-1 and Angiotensin II Signaling to Mediate Endothelial Dysfunction and MAPK Activation in Guinea-Pig Hearts

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Emilia Wojtera

2014-10-01

Full Text Available We hypothesized that, due to a cross-talk between cytoplasmic O2−-sources and intraluminally expressed xanthine oxidase (XO, intraluminal O2− is instrumental in mediating intraluminal (endothelial dysfunction and cytosolic (p38 and ERK1/2 MAPKs phosphorylation manifestations of vascular oxidative stress induced by endothelin-1 (ET-1 and angiotensin II (AT-II. Isolated guinea-pig hearts were subjected to 10-min agonist perfusion causing a burst of an intraluminal O2−. ET-1 antagonist, tezosentan, attenuated AT-II-mediated O2−, indicating its partial ET-1 mediation. ET-1 and Ang-T (AT-II + tezosentan triggered intraluminal O2−, endothelial dysfunction, MAPKs and p47phox phosphorylation, and NADPH oxidase (Nox and XO activation. These effects were: (i prevented by blocking PKC (chelerythrine, Nox (apocynin, mitochondrial ATP-dependent K+ channel (5-HD, complex II (TTFA, and XO (allopurinol; (ii mimicked by the activation of Nox (NADH; and mitochondria (diazoxide, 3-NPA and (iii the effects by NADH were prevented by 5-HD, TTFA and chelerythrine, and those by diazoxide and 3-NPA by apocynin and chelerythrine, suggesting that the agonists coactivate Nox and mitochondria, which further amplify their activity via PKC. The effects by ET-1, Ang-T, NADH, diazoxide, and 3-NPA were opposed by blocking intraluminal O2− (SOD and XO, and were mimicked by XO activation (hypoxanthine. Apocynin, TTFA, chelerythrine, and SOD opposed the effects by hypoxanthine. In conclusion, oxidative stress by agonists involves cellular inside-out and outside-in signaling in which Nox-mitochondria-PKC system and XO mutually maintain their activities via the intraluminal O2−.

Role of Shp2 in forebrain neurons in regulating metabolic and cardiovascular functions and responses to leptin.

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do Carmo, J M; da Silva, A A; Sessums, P O; Ebaady, S H; Pace, B R; Rushing, J S; Davis, M T; Hall, J E

2014-06-01

We examined whether deficiency of Src homology 2 containing phosphatase (Shp2) signaling in forebrain neurons alters metabolic and cardiovascular regulation under various conditions and if it attenuates the anorexic and cardiovascular effects of leptin. We also tested whether forebrain Shp2 deficiency alters blood pressure (BP) and heart rate (HR) responses to acute stress. Forebrain Shp2(-/-) mice were generated by crossing Shp2(flox/flox) mice with CamKIIα-cre mice. At 22-24 weeks of age, the mice were instrumented for telemetry for measurement of BP, HR and body temperature (BT). Oxygen consumption (VO2), energy expenditure and motor activity were monitored by indirect calorimetry. Shp2/CamKIIα-cre mice were heavier (46±3 vs 32±1 g), hyperglycemic, hyperleptinemic, hyperinsulinemic and hyperphagic compared to Shp2(flox/flox) control mice. Shp2/CamKIIα-cre mice exhibited reduced food intake responses to fasting/refeeding and impaired regulation of BT when exposed to 15 and 30 °C ambient temperatures. Despite being obese and having many features of metabolic syndrome, Shp2/CamKIIα-cre mice had similar daily average BP and HR compared to Shp2(flox/flox) mice (112±2 vs 113±1 mm Hg and 595±34 vs 650±40 b.p.m.), but exhibited increased BP and HR responses to cold exposure and acute air-jet stress test. Leptin's ability to reduce food intake and to raise BP were markedly attenuated in Shp2/CamKIIα-cre mice. These results suggest that forebrain Shp2 signaling regulates food intake, appetite responses to caloric deprivation and thermogenic control of body temperature during variations in ambient temperature. Deficiency of Shp2 signaling in the forebrain is associated with augmented cardiovascular responses to cold and acute stress but attenuated BP responses to leptin.

Changes in phosphatidylcholine fatty acid composition are associated with altered skeletal muscle insulin responsiveness in normal man.

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Clore, J N; Harris, P A; Li, J; Azzam, A; Gill, R; Zuelzer, W; Rizzo, W B; Blackard, W G

2000-02-01

The fatty acid composition of skeletal muscle cell membrane phospholipids (PLs) is known to influence insulin responsiveness in man. We have recently shown that the fatty acid composition of phosphatidylcholine (PC), and not phosphatidylethanolamine (PE), from skeletal muscle membranes is of particular importance in this relationship. Efforts to alter the PL fatty acid composition in animal models have demonstrated induction of insulin resistance. However, it has been more difficult to determine if changes in insulin sensitivity are associated with changes in the skeletal muscle membrane fatty acid composition of PL in man. Using nicotinic acid (NA), an agent known to induce insulin resistance in man, 9 normal subjects were studied before and after treatment for 1 month. Skeletal muscle membrane fatty acid composition of PC and PE from biopsies of vastus lateralis was correlated with insulin responsiveness using a 3-step hyperinsulinemic-euglycemic clamp. Treatment with NA was associated with a 25% increase in the half-maximal insulin concentration ([ED50] 52.0 +/- 7.5 to 64.6 +/- 9.0 microU/mL, P insulin sensitivity. Significant changes in the fatty acid composition of PC, but not PE, were also observed after NA administration. An increase in the percentage of 16:0 (21% +/- 0.3% to 21.7% +/- 0.4%, P insulin resistance with NA is associated with changes in the fatty acid composition of PC in man.

Pathophysiological Characteristics Underlying Different Glucose Response Curves

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Hulman, Adam; Witte, Daniel R; Vistisen, Dorte

2018-01-01

different glucose curve patterns and studied their stability and reproducibility over 3 years of follow-up. RESEARCH DESIGN AND METHODS: We analyzed data from participants without diabetes from the observational cohort from the European Group for the Study of Insulin Resistance: Relationship between Insulin...... and secretion. The glucose patterns identified at follow-up were similar to those at baseline, suggesting that the latent class method is robust. We integrated our classification model into an easy-to-use online application that facilitates the assessment of glucose curve patterns for other studies. CONCLUSIONS...... Sensitivity and Cardiovascular Disease study; participants had a five-time point OGTT at baseline (n = 1,443) and after 3 years (n = 1,045). Measures of insulin sensitivity and secretion were assessed at baseline with a euglycemic-hyperinsulinemic clamp and intravenous glucose tolerance test. Heterogeneous...

Gliadin Fragments and a Specific Gliadin 33-mer Peptide Close KATP Channels and Induce Insulin Secretion in INS-1E Cells and Rat Islets of Langerhans

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Dall, Morten; Calloe, Kirstine; Haupt-Jorgensen, Martin

2013-01-01

. A similar effect was observed in isolated rat islets (1.6-fold increase). In INS-1E cells, diazoxide reduced the stimulatory effect of gliadin digest. Additionally, gliadin digest was shown to decrease current through KATP-channels. A specific gliadin 33-mer had a similar effect, both on current and insulin...

Strategies used by Patients with Type 1 Diabetes to Avoid Hypoglycemia in a 24×1-Hour Marathon: Comparison with the Amounts of Carbohydrates Estimated by a Customizable Algorithm.

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Buoite Stella, Alex; Assaloni, Roberta; Tonutti, Laura; Manca, Elena; Tortul, Carla; Candido, Riccardo; Francescato, Maria Pia

2017-04-01

The preferred countermeasure to avoid exercise-related hypoglycemia was investigated in a group of patients with type 1 diabetes participating in a stressful event, a 24×1-hour relay marathon. The carbohydrates actually consumed were compared to those estimated for each patient by applying a customizable algorithm, Exercise Carbohydrates Requirement Estimating Software (ECRES), based on patient's usual therapy and diet and on the exercise characteristics. Glycemia was tested at the start, middle and end of the races. Usual therapies and diets and the adopted countermeasures were recorded in detail. We studied 19 patients who walked/ran 10.4±2.8 km with a heart rate of 167±11 beats per minute. Of the 19 patients, 7 patients reduced the administered insulin (premeal bolus or basal infusion rate). Glycemia fell by the end of the races (p=0.006; median -1.8 mmol⋅L -1 ; interquartile range -0.4 mmol⋅L -1 to -5.3 mmol⋅L -1 ), despite 9 patients being hyperglycemic at the start. Of the patients, 14 concluded the race with glycemia on target, and 4 patients were hyperglycemic. Amounts of carbohydrates actually consumed (median 30 g; interquartile range 0 g to 71 g) were not significantly different from those estimated by ECRES (median 38 g; interquartile range 24 g to 68 g), the 2 quantities being significantly related (R=0.64; p=0.003). ECRES estimated lower carbohydrate levels (-13 g) than the amounts actually consumed by the 4 patients who concluded their exercises with hyperglycemia. Patients preferred to consume extra carbohydrates to avoid the possible exercise-induced hypoglycemia. ECRES would provide satisfactory estimates of the carbohydrate requirements, even for a stressful condition, and almost equal to the quantities consumed following medical advice. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Lifetime Exposure to a Constant Environment Amplifies the Impact of a Fructose-Rich Diet on Glucose Homeostasis during Pregnancy

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Song, Aleida; Astbury, Stuart; Hoedl, Abha; Nielsen, Brent; Symonds, Michael E.; Bell, Rhonda C.

2017-01-01

The need to refine rodent models of human-related disease is now being recognized, in particular the rearing environment that can profoundly modulate metabolic regulation. Most studies on pregnancy and fetal development purchase and transport young females into the research facility, which after a short period of acclimation are investigated (Gen0). We demonstrate that female offspring (Gen1) show an exaggerated hyperinsulinemic response to pregnancy when fed a standard diet and with high fru...

Glucose-dependent insulinotropic polypeptide

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Christensen, Mikkel; Vedtofte, Louise; Holst, Jens Juul

2011-01-01

of GIP were administered intravenously (randomized and double blinded) during 90 min of insulin-induced hypoglycemia, euglycemia, or hyperglycemia. RESULTS During hypoglycemia, GIP infusion caused greater glucagon responses during the first 30 min compared with saline (76 ± 17 vs. 28 ± 16 pmol/L per 30...... min, P hyperglycemia, comparable suppression of plasma glucagon (-461 ± 81 vs. -371 ± 50 pmol/L per 90 min......, P = 0.26) was observed with GIP and saline infusions. In addition, during hyperglycemia, GIP more than doubled the insulin secretion rate (P hyperglycemia while strongly potentiating insulin secretion...

Dietary change: what are the responses and roles of significant others?

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Paisley, Judy; Beanlands, Heather; Goldman, Joanne; Evers, Susan; Chappell, Janet

2008-01-01

This study examined the impact of one person's dietary change on the experiences of a significant other with whom they regularly shared meals. Qualitative constant comparison approach using semistructured interviews. Community-based. Forty-two participants were recruited using a stratified purposive sampling strategy. Verbatim transcripts were analyzed using NUD*IST, version 4.0 software (Qualitative Solutions and Research, Melbourne, Australia, 1997) and manual coding. Most dietary changers had modified their diets in response to a disease diagnosis (eg, cardiovascular disease, diabetes, cancer, hypoglycemia, acquired immunodeficiency syndrome (AIDS), ulcer, allergies). Others had changed their diets for personal reasons (eg, weight loss, vegetarian diets). The dietary changes included dietary fat reduction, conversion to vegetarian or vegan diets, restriction of total kilocalorie intake, and elimination or reduction of specific food items. Significant others described a range of emotional responses to the dietary change, including cooperation, encouragement, skepticism, and anger. Significant others' descriptions of the roles that they played in the dietary change were positive (enabling), neutral (neither enabling nor inhibiting), or negative (inhibiting). Most significant others played positive roles; few played neutral or negative roles. Understanding dietary change from the perspective of significant others can enable nutrition professionals to develop strategies to promote dietary modifications as a shared activity.

Polycystic ovary disease. A risk factor for gestational diabetes?

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Lanzone, A; Caruso, A; Di Simone, N; De Carolis, S; Fulghesu, A M; Mancuso, S

1995-04-01

We investigated the impact of pregestationally elevated insulin plasma levels on glycemic control in pregnant women with polycystic ovary disease (PCOD). Twelve patients with PCOD who became pregnant within six months following evaluation of their metabolic status were the study subjects. Four were obese and six (two obese) had a hyperinsulinemic response to the oral glucose tolerance test (OGTT). They were tested with the OGTT at 28-30 weeks of gestation. We also tested 12 normal patients and 10 consecutive patients with gestational diabetes; all were at the same gestational age. Plasma levels of insulin and glucose were determined in the samples collected for a period of four hours after glucose load (100 g). All PCOD patients significantly increased their insulin secretion in pregnancy. The hyperinsulinemic PCOD patients developed gestational diabetes (two patients) and impaired gestational glucose tolerance (three patients). The area under the insulin curve was greater in PCOD patients than in control and gestational diabetes patients (P PCOD may develop a derangement of glycemic control, probably related to their pregestational insulinemic status.

Defects in α-Cell Function in Patients With Diabetes Due to Chronic Pancreatitis Compared With Patients With Type 2 Diabetes and Healthy Individuals

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Mumme, Lena; Breuer, Thomas G K; Rohrer, Stephan

2017-01-01

.0002) but not in patients with chronic pancreatitis. CONCLUSIONS: α-Cell responses to oral glucose ingestion and to hypoglycemia are disturbed in patients with diabetes and chronic pancreatitis and in patients with type 2 diabetes. The similarities between these defects suggest a common etiology.......OBJECTIVE: Diabetes frequently develops in patients with chronic pancreatitis. We examined the alterations in the glucagon response to hypoglycemia and to oral glucose administration in patients with diabetes due to chronic pancreatitis. RESEARCH DESIGN AND METHODS: Ten patients with diabetes...... secondary to chronic pancreatitis were compared with 13 patients with type 2 diabetes and 10 healthy control subjects. A stepwise hypoglycemic clamp and an oral glucose tolerance test (OGTT) were performed. RESULTS: Glucose levels during the OGTT were higher in patients with diabetes and chronic...

A case of hypoglycemiainduced QT prolongation leading to torsade de pointes and a review of pathophysiological mechanisms

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Faris Hannoodi

2017-06-01

Full Text Available Torsades de pointes is a life-threatening cardiac arrhythmia. Occurrence of this arrhythmia as a result of hypoglycemia has not been reported in the literature. We describe an interesting case of an insulindependent diabetic patient presenting with torsades de pointes resulting from hypoglycemia. A 62-year-old male was admitted to the hospital following an episode of severe insulin-induced hypoglycemia and a cardiac arrest. He was found to unresponsive at home after taking insulin. His serum glucose was found to be 18. He was given juice initially to normalize his glucose and was then transferred by EMS to ER where he was given 5% dextrose infusion. Analysis of the LifeVest rhythm recording showed torsades de pointes that was terminated by defibrillation of the LifeVest. Several mechanisms are responsible for torsade, including QT interval prolongation, adrenalin secretion and calcium overload leading to intracellular calcium oscillations. These mechanisms are a trigger to torsade de pointes. Predisposing factors were present leading torsade to occur.

In vivo cardiac glucose metabolism in the high-fat fed mouse: Comparison of euglycemic–hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach

International Nuclear Information System (INIS)

Kowalski, Greg M.; De Souza, David P.; Risis, Steve; Burch, Micah L.; Hamley, Steven; Kloehn, Joachim; Selathurai, Ahrathy; Lee-Young, Robert S.; Tull, Dedreia; O'Callaghan, Sean; McConville, Malcolm J.; Bruce, Clinton R.

2015-01-01

Rationale: Cardiac metabolism is thought to be altered in insulin resistance and type 2 diabetes (T2D). Our understanding of the regulation of cardiac substrate metabolism and insulin sensitivity has largely been derived from ex vivo preparations which are not subject to the same metabolic regulation as in the intact heart in vivo. Studies are therefore required to examine in vivo cardiac glucose metabolism under physiologically relevant conditions. Objective: To determine the temporal pattern of the development of cardiac insulin resistance and to compare with dynamic approaches to interrogate cardiac glucose and intermediary metabolism in vivo. Methods and results: Studies were conducted to determine the evolution of cardiac insulin resistance in C57Bl/6 mice fed a high-fat diet (HFD) for between 1 and 16 weeks. Dynamic in vivo cardiac glucose metabolism was determined following oral administration of [U- 13 C] glucose. Hearts were collected after 15 and 60 min and flux profiling was determined by measuring 13 C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates. Cardiac insulin resistance, determined by euglycemic–hyperinsulinemic clamp, was evident after 3 weeks of HFD. Despite the presence of insulin resistance, in vivo cardiac glucose metabolism following oral glucose administration was not compromised in HFD mice. This contrasts our recent findings in skeletal muscle, where TCA cycle activity was reduced in mice fed a HFD. Similar to our report in muscle, glucose derived pyruvate entry into the TCA cycle in the heart was almost exclusively via pyruvate dehydrogenase, with pyruvate carboxylase mediated anaplerosis being negligible after oral glucose administration. Conclusions: Under experimental conditions which closely mimic the postprandial state, the insulin resistant mouse heart retains the ability to stimulate glucose metabolism. - Highlights: • Insulin clamp was used to determine the evolution of cardiac insulin

Patient Safety Learning Laboratory: Making Acute Care More Patient-Centered

Science.gov (United States)

2017-03-22

Central Line-Associated Bloodstream Infection (CLABSI); Venous Thromboembolism; Patient Fall; Catheter-Associated Infection; Severe Hypoglycemia; Opioid-Related Severe Adverse Drug Event; Hospital Acquired Pressure Ulcer; Adverse Drug Event; Severe Hospital Acquired Delerium; Rapid Response Related to Arrhythmia

The dissociation of tumor-induced weight loss from hypoglycemia in a transplantable pluripotent rat islet tumor results in the segregation of stable alpha- and beta-cell tumor phenotypes

DEFF Research Database (Denmark)

Madsen, O D; Karlsen, C; Nielsen, E

1993-01-01

in NEDH rats resulted in stable hypoglycemic insulinoma tumor lines, such as MSL-G2-IN. Occasionally, hypoglycemia as well as severe weight loss were observed in the early tumor passages of MSL-G and the subclone, NHI-5B, which carry the transfected neomycin and human insulin genes as unique clonal...... markers. By selective transplantation, it was possible to segregate stable anorectic normoglycemic tumor lines, MSL-G-AN and NHI-5B-AN, from both clones. These tumors cause an abrupt onset of anorexia when they reach a size of 400-500 mg (loss parallels...... a common clonal origin of pluripotent MSL cells, thus supporting the existence of a cell lineage relationship between islet alpha- and beta-cell during ontogeny; and 2) that our glucagonomas release an anorexigenic substance(s) of unknown nature that causes a severe weight loss comparable to that reported...

Lys169 of human glucokinase is a determinant for glucose phosphorylation: implication for the atomic mechanism of glucokinase catalysis.

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Jian Zhang

Full Text Available Glucokinase (GK, a glucose sensor, maintains plasma glucose homeostasis via phosphorylation of glucose and is a potential therapeutic target for treating maturity-onset diabetes of the young (MODY and persistent hyperinsulinemic hypoglycemia of infancy (PHHI. To characterize the catalytic mechanism of glucose phosphorylation by GK, we combined molecular modeling, molecular dynamics (MD simulations, quantum mechanics/molecular mechanics (QM/MM calculations, experimental mutagenesis and enzymatic kinetic analysis on both wild-type and mutated GK. Our three-dimensional (3D model of the GK-Mg(2+-ATP-glucose (GMAG complex, is in agreement with a large number of mutagenesis data, and elucidates atomic information of the catalytic site in GK for glucose phosphorylation. A 10-ns MD simulation of the GMAG complex revealed that Lys169 plays a dominant role in glucose phosphorylation. This prediction was verified by experimental mutagenesis of GK (K169A and enzymatic kinetic analyses of glucose phosphorylation. QM/MM calculations were further used to study the role of Lys169 in the catalytic mechanism of the glucose phosphorylation and we found that Lys169 enhances the binding of GK with both ATP and glucose by serving as a bridge between ATP and glucose. More importantly, Lys169 directly participates in the glucose phosphorylation as a general acid catalyst. Our findings provide mechanistic details of glucose phorphorylation catalyzed by GK, and are important for understanding the pathogenic mechanism of MODY.

GKAs for diabetes therapy: why no clinically useful drug after two decades of trying?

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Matschinsky, Franz M

2013-02-01

Results of basic biochemical and physiological research, strongly endorsed by findings in human pathophysiology and genetics, had characterized the glucose phosphorylating enzyme glucokinase as a critical player in normal glucose homeostasis, diabetes mellitus, and hyperinsulinemic hypoglycemia, and identified the enzyme as a promising new drug target. R&D initiated in the early 1990s and directed at this target discovered glucokinase activators (GKAs) as a new class of potentially antidiabetic drugs. GKAs were characterized as nonessential allosteric activators that increase glucose affinity and V(max) of the enzyme, thus stimulating glucose metabolism in glucokinase expressing tissue, of foremost functional significance in the insulin producing pancreatic beta cells and the liver. The results of preclinical testing of GKAs by many pharmaceutical companies demonstrated uniformly high hypoglycemic efficacy in normal and diabetic animals. GKAs were also highly effective in Phase I trials in patients with type 2 diabetes mellitus (T2DM). However, results of a recent Phase II trial were less encouraging because patients developed hyperlipidemia and vascular hypertension, and the drug lost efficacy within several months. This outcome is prompting a reappraisal of the GKA strategy. In this opinion article, the 'pros and cons' of the strategy to use these compounds in diabetes management are critically reexamined and suggestions are made that might facilitate progress of GKA R&D that could still result in a novel antidiabetic medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mosaic Turner syndrome and hyperinsulinaemic hypoglycaemia

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Alkhayyat, H.; Christesen, Henrik Thybo; Steer, J.

2006-01-01

BACKGROUND: A common and well recognised feature of Turner's syndrome (partial or total monosomy X) is impaired glucose tolerance or type 2 diabetes mellitus. A small percentage of patients with Turner's syndrome have a complex mosaic karyotype with atypical clinical features and mental retardation....... METHODS/PATIENT: We report the first case of a child with a complex mosaic Turner genotype and hyperinsulinaemic hypoglycaemia responsive to diazoxide therapy. RESULTS: Cytogenetic analysis showed four cell lines: one with 45,X; the others with an additional small ring chromosome, a small marker...... chromosome, and both the ring and marker chromosomes, respectively. FISH studies showed the abnormal chromosomes to originate from an X. The X inactivation locus (XIST) was present in the ring, but not in the marker chromosome. CONCLUSIONS: The recognition of hypoglycaemia in children with atypical Turner...

Defects in α-Cell Function in Patients With Diabetes Due to Chronic Pancreatitis Compared With Patients With Type 2 Diabetes and Healthy Individuals.

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Mumme, Lena; Breuer, Thomas G K; Rohrer, Stephan; Schenker, Nina; Menge, Björn A; Holst, Jens J; Nauck, Michael A; Meier, Juris J

2017-10-01

Diabetes frequently develops in patients with chronic pancreatitis. We examined the alterations in the glucagon response to hypoglycemia and to oral glucose administration in patients with diabetes due to chronic pancreatitis. Ten patients with diabetes secondary to chronic pancreatitis were compared with 13 patients with type 2 diabetes and 10 healthy control subjects. A stepwise hypoglycemic clamp and an oral glucose tolerance test (OGTT) were performed. Glucose levels during the OGTT were higher in patients with diabetes and chronic pancreatitis and lower in control subjects ( P chronic pancreatitis and with type 2 diabetes ( P chronic pancreatitis. α-Cell responses to oral glucose ingestion and to hypoglycemia are disturbed in patients with diabetes and chronic pancreatitis and in patients with type 2 diabetes. The similarities between these defects suggest a common etiology. © 2017 by the American Diabetes Association.

Hypoglycemia

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... body breaks down carbohydrates from foods — such as bread, rice, pasta, vegetables, fruit and milk products — into ... which is used to treat malaria. Excessive alcohol consumption. Drinking heavily without eating can block your liver ...

Hypoglycemia

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... fall too low, the body releases the hormone adrenaline, which helps get stored glucose into the bloodstream ... heart rate are early warning signs of this adrenaline release. More severe symptoms — such as confusion, drowsiness, ...

Protection of hypoglycemia-induced neuronal death by β-hydroxybutyrate involves the preservation of energy levels and decreased production of reactive oxygen species.

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Julio-Amilpas, Alberto; Montiel, Teresa; Soto-Tinoco, Eva; Gerónimo-Olvera, Cristian; Massieu, Lourdes

2015-05-01

Glucose is the main energy substrate in brain but in certain circumstances such as prolonged fasting and the suckling period alternative substrates can be used such as the ketone bodies (KB), beta-hydroxybutyrate (BHB), and acetoacetate. It has been shown that KB prevent neuronal death induced during energy limiting conditions and excitotoxicity. The protective effect of KB has been mainly attributed to the improvement of mitochondrial function. In the present study, we have investigated the protective effect of D-BHB against neuronal death induced by severe noncoma hypoglycemia in the rat in vivo and by glucose deprivation (GD) in cortical cultures. Results show that systemic administration of D-BHB reduces reactive oxygen species (ROS) production in distinct cortical areas and subregions of the hippocampus and efficiently prevents neuronal death in the cortex of hypoglycemic animals. In vitro results show that D-BHB stimulates ATP production and reduces ROS levels, while the nonphysiologic isomer of BHB, L-BHB, has no effect on energy production but reduces ROS levels. Data suggest that protection by BHB, not only results from its metabolic action but is also related to its capability to reduce ROS, rendering this KB as a suitable candidate for the treatment of ischemic and traumatic injury.

Zinc transporter ZIP14 functions in hepatic zinc, iron and glucose homeostasis during the innate immune response (endotoxemia.

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Tolunay Beker Aydemir

Full Text Available ZIP14 (slc39A14 is a zinc transporter induced in response to pro-inflammatory stimuli. ZIP14 induction accompanies the reduction in serum zinc (hypozincemia of acute inflammation. ZIP14 can transport Zn(2+ and non-transferrin-bound Fe(2+ in vitro. Using a Zip14(-/- mouse model we demonstrated that ZIP14 was essential for control of phosphatase PTP1B activity and phosphorylation of c-Met during liver regeneration. In the current studies, a global screening of ZIP transporter gene expression in response to LPS-induced endotoxemia was conducted. Following LPS, Zip14 was the most highly up-regulated Zip transcript in liver, but also in white adipose tissue and muscle. Using ZIP14(-/- mice we show that ZIP14 contributes to zinc absorption from the gastrointestinal tract directly or indirectly as zinc absorption was decreased in the KOs. In contrast, Zip14(-/- mice absorbed more iron. The Zip14 KO mice did not exhibit hypozincemia following LPS, but do have hypoferremia. Livers of Zip14-/- mice had increased transcript abundance for hepcidin, divalent metal transporter-1, ferritin and transferrin receptor-1 and greater accumulation of iron. The Zip14(-/- phenotype included greater body fat, hypoglycemia and higher insulin levels, as well as increased liver glucose and greater phosphorylation of the insulin receptor and increased GLUT2, SREBP-1c and FASN expression. The Zip14 KO mice exhibited decreased circulating IL-6 with increased hepatic SOCS-3 following LPS, suggesting SOCS-3 inhibited insulin signaling which produced the hypoglycemia in this genotype. The results are consistent with ZIP14 ablation yielding abnormal labile zinc pools which lead to increased SOCS-3 production through G-coupled receptor activation and increased cAMP production as well as signaled by increased pSTAT3 via the IL-6 receptor, which inhibits IRS 1/2 phosphorylation. Our data show the role of ZIP14 in the hepatocyte is multi-functional since zinc and iron trafficking are

Predicting the 6-month risk of severe hypoglycemia among adults with diabetes: Development and external validation of a prediction model.

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Schroeder, Emily B; Xu, Stan; Goodrich, Glenn K; Nichols, Gregory A; O'Connor, Patrick J; Steiner, John F

2017-07-01

To develop and externally validate a prediction model for the 6-month risk of a severe hypoglycemic event among individuals with pharmacologically treated diabetes. The development cohort consisted of 31,674 Kaiser Permanente Colorado members with pharmacologically treated diabetes (2007-2015). The validation cohorts consisted of 38,764 Kaiser Permanente Northwest members and 12,035 HealthPartners members. Variables were chosen that would be available in electronic health records. We developed 16-variable and 6-variable models, using a Cox counting model process that allows for the inclusion of multiple 6-month observation periods per person. Across the three cohorts, there were 850,992 6-month observation periods, and 10,448 periods with at least one severe hypoglycemic event. The six-variable model contained age, diabetes type, HgbA1c, eGFR, history of a hypoglycemic event in the prior year, and insulin use. Both prediction models performed well, with good calibration and c-statistics of 0.84 and 0.81 for the 16-variable and 6-variable models, respectively. In the external validation cohorts, the c-statistics were 0.80-0.84. We developed and validated two prediction models for predicting the 6-month risk of hypoglycemia. The 16-variable model had slightly better performance than the 6-variable model, but in some practice settings, use of the simpler model may be preferred. Copyright © 2017 Elsevier Inc. All rights reserved.

Glucose sensing by carotid body glomus cells: potential implications in disease

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Lin eGao

2014-10-01

Full Text Available The carotid body (CB is a key chemoreceptor organ in which glomus cells sense changes in blood O2, CO2, and pH levels. CB glomus cells have also been found to detect hypoglycemia in both non-primate mammals and humans. O2 and low-glucose responses share a common final pathway involving membrane depolarization, extracellular calcium influx, increase in cytosolic calcium concentration, and neurotransmitter secretion, which stimulates afferent sensory fibers to evoke sympathoadrenal activation. On the other hand, hypoxia and low glucose induce separate signal transduction pathways. Unlike O2 sensing, the response of the CB to low glucose is not altered by rotenone, with the low glucose-activated background cationic current unaffected by hypoxia. Responses of the CB to hypoglycemia and hypoxia can be potentiated by each other. The counter-regulatory response to hypoglycemia by the CB is essential for the brain, an organ that is particularly sensitive to low glucose. CB glucose sensing could be altered in diabetic patients, particularly those under insulin treatment, as well as in other medical conditions such as sleep apnea or obstructive pulmonary diseases, where chronic hypoxemia presents with plastic modifications in CB structure and function. The current review will focus on the following main aspects: 1 the CB as a low glucose sensor in both in vitro and in vivo models; 2 molecular and ionic mechanisms of low glucose sensing by glomus cells, 3 the interplay between low glucose and O2 sensing in CB, and 4 the role of CB low glucose sensing in the pathophysiology of cardiorespiratory and metabolic diseases, and how this may serve as a potential therapeutic target.

In vivo cardiac glucose metabolism in the high-fat fed mouse: Comparison of euglycemic–hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach

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Kowalski, Greg M., E-mail: greg.kowalski@deakin.edu.au [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); De Souza, David P. [Metabolomics Australia, Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Risis, Steve [Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004 (Australia); Burch, Micah L. [Brigham and Women' s Hospital, Department of Medicine, Boston, MA (United States); Hamley, Steven [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); Kloehn, Joachim [Metabolomics Australia, Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Selathurai, Ahrathy [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); Lee-Young, Robert S. [Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004 (Australia); Tull, Dedreia; O' Callaghan, Sean; McConville, Malcolm J. [Metabolomics Australia, Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Bruce, Clinton R. [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia)

2015-08-07

Rationale: Cardiac metabolism is thought to be altered in insulin resistance and type 2 diabetes (T2D). Our understanding of the regulation of cardiac substrate metabolism and insulin sensitivity has largely been derived from ex vivo preparations which are not subject to the same metabolic regulation as in the intact heart in vivo. Studies are therefore required to examine in vivo cardiac glucose metabolism under physiologically relevant conditions. Objective: To determine the temporal pattern of the development of cardiac insulin resistance and to compare with dynamic approaches to interrogate cardiac glucose and intermediary metabolism in vivo. Methods and results: Studies were conducted to determine the evolution of cardiac insulin resistance in C57Bl/6 mice fed a high-fat diet (HFD) for between 1 and 16 weeks. Dynamic in vivo cardiac glucose metabolism was determined following oral administration of [U-{sup 13}C] glucose. Hearts were collected after 15 and 60 min and flux profiling was determined by measuring {sup 13}C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates. Cardiac insulin resistance, determined by euglycemic–hyperinsulinemic clamp, was evident after 3 weeks of HFD. Despite the presence of insulin resistance, in vivo cardiac glucose metabolism following oral glucose administration was not compromised in HFD mice. This contrasts our recent findings in skeletal muscle, where TCA cycle activity was reduced in mice fed a HFD. Similar to our report in muscle, glucose derived pyruvate entry into the TCA cycle in the heart was almost exclusively via pyruvate dehydrogenase, with pyruvate carboxylase mediated anaplerosis being negligible after oral glucose administration. Conclusions: Under experimental conditions which closely mimic the postprandial state, the insulin resistant mouse heart retains the ability to stimulate glucose metabolism. - Highlights: • Insulin clamp was used to determine the evolution of cardiac

Fasting during Ramadan: efficacy, safety, and patient acceptability of vildagliptin in diabetic patients

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Aziz KMA

2015-04-01

Full Text Available Kamran MA Aziz Aseer Diabetes Center, Aseer Central Hospital, Ministry of Health, Abha, Saudi Arabia Abstract: Diabetes management during Ramadan fasting is challenging to the physician in terms of minimizing the risk of hypoglycemia. As compared to oral hypoglycemic agents (OHAs and sulfonylureas (SUs, which carry a higher and significant risk of hypoglycemia, newer antidiabetic agents such as dipeptidyl peptidase-4 (DPP-4 inhibitors have demonstrated lower risk of hypoglycemia during Ramadan fasting, with better patient compliance. In addition to diabetes education and pre-Ramadan assessments, the physician should also consider use of DPP-4 inhibitors (such as vildagliptin during Ramadan fasting to minimize the risk of hypoglycemia in type 2 diabetic subjects. Severe episodes of hypoglycemia have been demonstrated in recent research and clinical trials with OHAs/SUs. Conversely, these research observations have also demonstrated comparative safety and efficacy with lower risk of hypoglycemia associated with vildagliptin. Current research review has collected evidence-based clinical trials and observations for the drug vildagliptin to minimize the risk of hypoglycemia during Ramadan fasting, while at the same time focusing the role of diabetes self-management education (DSME, pre-Ramadan assessments, and patient care. Keywords: hypoglycemia, DPP4-inhibitors, oral hypoglycemic agents, Ramadan fasting, type 2 diabetes, vildagliptin

Incapacity of the Mind Secondary to Medication Misuse as a Not Criminally Responsible Defense.

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Prat, Sebastien S; Losier, Bruno J; Moulden, Heather M; Chaimowitz, Gary A

2017-01-01

The manifestations of disorders of the mind may play a role in the occurrence of criminal behavior. In the majority of the cases, the presence of a psychiatric disorder is cited as the reason that an individual was not fully aware of his behavior. However, other conditions, such as seizure disorders or hypoglycemia, have also been linked to an inability to understand the nature and consequences of one's actions. On occasion, these situations can be explained by a state of automatism that may be described as insane or noninsane. In this article, we describe the case of a 77-year-old man, suffering from Parkinson's disease, where the issue of criminal responsibility associated with incapacity of the mind secondary to medication misuse was raised. We elaborate on the thinking behind this opinion and the implications according to Canadian law. Although the legal outcome of this case is specific to our jurisdiction, the clinical implication may be common to any patient suffering from a similar condition and may inform physicians, families, and lawyers. © 2016 American Academy of Forensic Sciences.

Insulin sensitivity, fat distribution, and adipocytokine response to different diets in lean and obese cats before and after weight loss.

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Hoenig, M; Thomaseth, K; Waldron, M; Ferguson, D C

2007-01-01

Obesity is a major health problem in cats and a risk factor for diabetes. It has been postulated that cats are always gluconeogenic and that the rise in obesity might be related to high dietary carbohydrates. We examined the effect of a high-carbohydrate/low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on glucose and fat metabolism during euglycemic hyperinsulinemic clamp, adipocytokines, and fat distribution in 12 lean and 16 obese cats before and after weight loss. Feeding diet HP led to greater heat production in lean but not in obese cats. Regardless of diet, obese cats had markedly decreased glucose effectiveness and insulin resistance, but greater suppression of nonesterified fatty acids during the euglycemic hyperinsulinemic clamp was seen in obese cats on diet HC compared with lean cats on either diet or obese cats on diet HP. In contrast to humans, obese cats had abdominal fat equally distributed subcutaneously and intra-abdominally. Weight loss normalized insulin sensitivity; however, increased nonesterified fatty acid suppression was maintained and fat loss was less in cats on diet HC. Adiponectin was negatively and leptin positively correlated with fat mass. Lean cats and cats during weight loss, but not obese cats, adapted to the varying dietary carbohydrate/protein content with changes in substrate oxidation. We conclude that diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats. These data also show that insulin sensitivity of glucose and fat metabolism can be differentially regulated in cats.

α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes

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Marcela Brissova

2018-03-01

Full Text Available Many patients with type 1 diabetes (T1D have residual β cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual β cells and α cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant β cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D α cells was markedly reduced, and these cells had alterations in transcription factors constituting α and β cell identity. In the native pancreas and after placing the T1D islets into a non-autoimmune, normoglycemic in vivo environment, there was no evidence of α-to-β cell conversion. These results suggest an explanation for the disordered T1D counterregulatory glucagon response to hypoglycemia.

Early enhancements of hepatic and later of peripheral insulin sensitivity combined with increased postprandial insulin secretion contribute to improved glycemic control after Roux-en-Y gastric bypass

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Bojsen-Møller, Kirstine N; Dirksen, Carsten; Jørgensen, Nils Bruun

2014-01-01

after RYGB. Participants were included after a preoperative diet induced total weight loss of -9.2±1.2%. Hepatic and peripheral insulin sensitivity were assessed using the hyperinsulinemic euglycemic clamp combined with glucose tracer technique and beta-cell function evaluated in response...... after surgery. Insulin mediated glucose disposal and suppression of fatty acids did not improve immediately after surgery but increased at 3 months and 1 year likely related to the reduction in body weight. Insulin secretion increased after RYGB, but only in patients with type 2 diabetes and only...

Islet transplantation as safe and efficacious method to restore glycemic control and to avoid severe hypoglycemia after donor organ failure in pancreas transplantation.

Science.gov (United States)

Gerber, Philipp A; Hochuli, Michel; Benediktsdottir, Bara D; Zuellig, Richard A; Tschopp, Oliver; Glenck, Michael; de Rougemont, Olivier; Oberkofler, Christian; Spinas, Giatgen A; Lehmann, Roger

2018-01-01

The aim of this study was to assess safety and efficacy of islet transplantation after initial pancreas transplantation with subsequent organ failure. Patients undergoing islet transplantation at our institution after pancreas organ failure were compared to a control group of patients with pancreas graft failure, but without islet transplantation and to a group receiving pancreas retransplantation. Ten patients underwent islet transplantation after initial pancreas transplantation failed and were followed for a median of 51 months. The primary end point of HbA1c islet transplantation and in all three patients in the pancreas retransplantation group, but by none of the patients in the group without retransplantation (n = 7). Insulin requirement was reduced by 50% after islet transplantation. Kidney function (eGFR) declined with a rate of -1.0 mL ± 1.2 mL/min/1.73 m 2 per year during follow-up after islet transplantation, which tended to be slower than in the group without retransplantation (P = .07). Islet transplantation after deceased donor pancreas transplant failure is a method that can safely improve glycemic control and reduce the incidence of severe hypoglycemia and thus establish similar glycemic control as after initial pancreas transplantation, despite the need of additional exogenous insulin. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors

International Nuclear Information System (INIS)

Daughaday, W.H.; Kapadia, M.

1989-01-01

The authors reported that serum and tumor from a hypoglycemic patient with a fibrosarcoma contained insulin-like growth factor II (IGF-II), mostly in a large molecular form designated big IGF-II. They now describe two additional patients with non-islet-cell tumor with hypoglycemia (NICTH) whose sera contained big IGF-II. Removal of the tumor eliminated most of the big IGF-II from the sera of two patients. Because specific IGF-binding proteins modify the bioactivity of IGFs, the sizes of the endogenous IGF-binding protein complexes were determined after neutral gel filtration through Sephadex G-200. Normally about 75% of IGFs are carried as a ternary complex of 150 kDa consisting of IGF, a growth hormone (GH)-dependent IGF-binding protein, and an acid-labile complexing component. The three patients with NICTH completely lacked the 150-kDa complex. IGF-II was present as a 60-kDa complex with variable contributions of smaller complexes. In the immediate postoperative period, a 110-kDa complex appeared rather than the expected 150-kDa complex. Abnormal IGF-II binding may be important in NICTH because the 150-kDa complexes cross the capillary membrane poorly. The smaller complexes present in our patients' sera would be expected to enter interstitial fluid readily, and a 4- to 5-fold increase in the fraction of IGFs reaching the target cells would result

Susceptibility of glucokinase-MODY mutants to inactivation by oxidative stress in pancreatic β-cells.

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Cullen, Kirsty S; Matschinsky, Franz M; Agius, Loranne; Arden, Catherine

2011-12-01

The posttranslational regulation of glucokinase (GK) differs in hepatocytes and pancreatic β-cells. We tested the hypothesis that GK mutants that cause maturity-onset diabetes of the young (GK-MODY) show compromised activity and posttranslational regulation in β-cells. Activity and protein expression of GK-MODY and persistent hyperinsulinemic hypoglycemia of infancy (PHHI) mutants were studied in β-cell (MIN6) and non-β-cell (H4IIE) models. Binding of GK to phosphofructo-2-kinase, fructose-2,6-bisphosphatase (PFK2/FBPase2) was studied by bimolecular fluorescence complementation in cell-based models. Nine of 11 GK-MODY mutants that have minimal effect on enzyme kinetics in vitro showed decreased specific activity relative to wild type when expressed in β-cells. A subset of these were stable in non-β-cells but showed increased inactivation in conditions of oxidative stress and partial reversal of inactivation by dithiothreitol. Unlike the GK-MODY mutants, four of five GK-PHHI mutants had similar specific activity to wild type and Y214C had higher activity than wild type. The GK-binding protein PFK2/FBPase2 protected wild-type GK from oxidative inactivation and the decreased stability of GK-MODY mutants correlated with decreased interaction with PFK2/FBPase2. Several GK-MODY mutants show posttranslational defects in β-cells characterized by increased susceptibility to oxidative stress and/or protein instability. Regulation of GK activity through modulation of thiol status may be a physiological regulatory mechanism for the control of GK activity in β-cells.

ABCC8 R1420H Loss-of-Function Variant in a Southwest American Indian Community: Association With Increased Birth Weight and Doubled Risk of Type 2 Diabetes.

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Baier, Leslie J; Muller, Yunhua Li; Remedi, Maria Sara; Traurig, Michael; Piaggi, Paolo; Wiessner, Gregory; Huang, Ke; Stacy, Alyssa; Kobes, Sayuko; Krakoff, Jonathan; Bennett, Peter H; Nelson, Robert G; Knowler, William C; Hanson, Robert L; Nichols, Colin G; Bogardus, Clifton

2015-12-01

Missense variants in KCNJ11 and ABCC8, which encode the KIR6.2 and SUR1 subunits of the β-cell KATP channel, have previously been implicated in type 2 diabetes, neonatal diabetes, and hyperinsulinemic hypoglycemia of infancy (HHI). To determine whether variation in these genes affects risk for type 2 diabetes or increased birth weight as a consequence of fetal hyperinsulinemia in Pima Indians, missense and common noncoding variants were analyzed in individuals living in the Gila River Indian Community. A R1420H variant in SUR1 (ABCC8) was identified in 3.3% of the population (N = 7,710). R1420H carriers had higher mean birth weights and a twofold increased risk for type 2 diabetes with a 7-year earlier onset age despite being leaner than noncarriers. One individual homozygous for R1420H was identified; retrospective review of his medical records was consistent with HHI and a diagnosis of diabetes at age 3.5 years. In vitro studies showed that the R1420H substitution decreases KATP channel activity. Identification of this loss-of-function variant in ABCC8 with a carrier frequency of 3.3% affects clinical care as homozygous inheritance and potential HHI will occur in 1/3,600 births in this American Indian population. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Mitochondrial K-ATP opening confers protection against lethal myocardial injury and ischaemia-induced arrhythmias in the rat heart via PI3K/Akt-dependent and -independent mechanisms

Czech Academy of Sciences Publication Activity Database

Matejíková, J.; Ravingerová, T.; Pancza, D.; Čarnická, S.; Kolář, František

2009-01-01

Roč. 87, č. 12 (2009), s. 1055-1062 ISSN 0008-4212 R&D Projects: GA ČR(CZ) GA305/07/0875; GA MŠk MEB080837 Grant - others:VEGA(SK) 2/0173/08; APVV(SK) SK-CZ-0049-07 Institutional research plan: CEZ:AV0Z50110509 Keywords : myocardial ischemia * diazoxide * PI3K/Akt Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.341, year: 2009

Glucose-responsive neurons of the paraventricular thalamus control sucrose-seeking behavior.

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Labouèbe, Gwenaël; Boutrel, Benjamin; Tarussio, David; Thorens, Bernard

2016-08-01

Feeding behavior is governed by homeostatic needs and motivational drive to obtain palatable foods. Here, we identify a population of glutamatergic neurons in the paraventricular thalamus of mice that express the glucose transporter Glut2 (encoded by Slc2a2) and project to the nucleus accumbens. These neurons are activated by hypoglycemia and, in freely moving mice, their activation by optogenetics or Slc2a2 inactivation increases motivated sucrose-seeking but not saccharin-seeking behavior. These neurons may control sugar overconsumption in obesity and diabetes.

Insulin signaling in skeletal muscle of HIV‐infected patients in response to endurance and strength training

DEFF Research Database (Denmark)

Broholm, Christa; Mathur, Neha; Hvid, Thine

2013-01-01

. Euglycemic-hyperinsulinemic clamps with muscle biopsies were performed before and after the training interventions. Fifteen age- and body mass index (BMI)-matched HIV-negative men served as a sedentary baseline group. Phosphorylation and total protein expression of insulin signaling molecules as well...... hexokinase II (HKII) protein. HIV-infected patients with lipodystrophy have decreased insulin-stimulated glucose uptake in skeletal muscle and defects in insulin-stimulated phosphorylation of Akt(thr308). Endurance and strength training increase insulin-stimulated glucose uptake in these patients......Human immunodeficiency virus (HIV)-infected patients with lipodystrophy have decreased insulin-stimulated glucose uptake. Both endurance and resistance training improve insulin-stimulated glucose uptake in skeletal muscle of HIV-infected patients, but the mechanisms are unknown. This study aims...

The association of admission blood glucose level with the clinical picture and prognosis in cardiogenic shock - Results from the CardShock Study.

Science.gov (United States)

Kataja, Anu; Tarvasmäki, Tuukka; Lassus, Johan; Cardoso, Jose; Mebazaa, Alexandre; Køber, Lars; Sionis, Alessandro; Spinar, Jindrich; Carubelli, Valentina; Banaszewski, Marek; Marino, Rossella; Parissis, John; Nieminen, Markku S; Harjola, Veli-Pekka

2017-01-01

Critically ill patients often present with hyperglycemia, regardless of previous history of diabetes mellitus (DM). Hyperglycemia has been associated with adverse outcome in acute myocardial infarction and acute heart failure. We investigated the association of admission blood glucose level with the clinical picture and short-term mortality in cardiogenic shock (CS). Consecutively enrolled CS patients were divided into five categories according to plasma glucose level at the time of enrolment: hypoglycemia (glucose glucose level of 211 CS patients was recorded. Glucose levels were distributed equally between normoglycemia (26% of patients), mild (27%), moderate (19%) and severe (25%) hyperglycemia, while hypoglycemia (2%) was rare. Severe hyperglycemia was associated with higher blood leukocyte count (17.3 (5.8) E9/L), higher lactate level (4.4 (3.3-8.4) mmol/L) and lower arterial pH (7.23 (0.14)) compared with normoglycemia or mild to moderate hyperglycemia (pblood glucose level has prognostic significance in CS. Mortality is highest among patients with severe hyperglycemia or hypoglycemia. Severe hyperglycemia is independently associated with high in-hospital mortality in CS. It is also associated with biomarkers of systemic hypoperfusion and stress response. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Vulnerability to oxidative stress in vitro in pathophysiology of mitochondrial short-chain acyl-CoA dehydrogenase deficiency: response to antioxidants.

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Zarazuela Zolkipli

Full Text Available OBJECTIVE: To elucidate the pathophysiology of SCAD deficient patients who have a unique neurological phenotype, among fatty acid oxidation disorders, with early developmental delay, CNS malformations, intractable seizures, myopathy and clinical signs suggesting oxidative stress. METHODS: We studied skin fibroblast cultures from patients homozygous for ACADS common variant c.625G>A (n = 10, compound heterozygous for c.625G>A/c.319C>T (n = 3 or homozygous for pathogenic c.319C>T (n = 2 and c.1138C>T (n = 2 mutations compared to fibroblasts from patients with carnitine palmitoyltransferase 2 (CPT2 (n = 5, mitochondrial trifunctional protein (MTP/long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD (n = 7, and medium-chain acyl-CoA dehydrogenase (MCAD deficiencies (n = 4 and normal controls (n = 9. All were exposed to 50 µM menadione at 37°C. Additional conditions included exposure to 39°C and/or hypoglycemia. Time to 100% cell death was confirmed with trypan blue dye exclusion. Experiments were repeated with antioxidants (Vitamins C and E or N-acetylcysteine, Bezafibrate or glucose and temperature rescue. RESULTS: The most significant risk factor for vulnerability to menadione-induced oxidative stress was the presence of a FAO defect. SCADD fibroblasts were the most vulnerable compared to other FAO disorders and controls, and were similarly affected, independent of genotype. Cell death was exacerbated by hyperthermia and/or hypoglycemia. Hyperthermia was a more significant independent risk factor than hypoglycemia. Rescue significantly prolonged survival. Incubation with antioxidants and Bezafibrate significantly increased viability of SCADD fibroblasts. INTERPRETATION: Vulnerability to oxidative stress likely contributes to neurotoxicity of SCADD regardless of ACADS genotype and is significantly exacerbated by hyperthermia. We recommend rigorous temperature control in SCADD patients during acute illness

Use of a variable tracer infusion method to determine glucose turnover in humans

International Nuclear Information System (INIS)

Molina, J.M.; Baron, A.D.; Edelman, S.V.; Brechtel, G.; Wallace, P.; Olefsky, J.M.

1990-01-01

The single-compartment pool fraction model, when used with the hyperinsulinemic glucose clamp technique to measure rates of glucose turnover, sometimes underestimates true rates of glucose appearance (Ra) resulting in negative values for hepatic glucose output (HGO). We focused our attention on isotope discrimination and model error as possible explanations for this underestimation. We found no difference in [3-3H] glucose specific activity in samples obtained simultaneously from the femoral artery and vein (2,400 +/- 455 vs. 2,454 +/- 522 dpm/mg) in 6 men during a hyperinsulinemic euglycemic clamp study where insulin was infused at 40 mU.m-2.min-1 for 3 h; therefore, isotope discrimination did not occur. We compared the ability of a constant (0.6 microCi/min) vs. variable tracer infusion method (tracer added to the glucose infusate) to measure non-steady-state Ra during hyperinsulinemic clamp studies. Plasma specific activity fell during the constant tracer infusion studies but did not change from base line during the variable tracer infusion studies. By maintaining a constant plasma specific activity the variable tracer infusion method eliminates uncertainty about changes in glucose pool size. This overcame modeling error and more accurately measures non-steady-state Ra (P less than 0.001 by analysis of variance vs. constant infusion method). In conclusion, underestimation of Ra determined isotopically during hyperinsulinemic clamp studies is largely due to modeling error that can be overcome by use of the variable tracer infusion method. This method allows more accurate determination of Ra and HGO under non-steady-state conditions

Improved glycemic control without hypoglycemia in elderly diabetic patients using the ubiquitous healthcare service, a new medical information system.

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Lim, Soo; Kang, Seon Mee; Shin, Hayley; Lee, Hak Jong; Won Yoon, Ji; Yu, Sung Hoon; Kim, So-Youn; Yoo, Soo Young; Jung, Hye Seung; Park, Kyong Soo; Ryu, Jun Oh; Jang, Hak C

2011-02-01

To improve quality and efficiency of care for elderly patients with type 2 diabetes, we introduced elderly-friendly strategies to the clinical decision support system (CDSS)-based ubiquitous healthcare (u-healthcare) service, which is an individualized health management system using advanced medical information technology. We conducted a 6-month randomized, controlled clinical trial involving 144 patients aged >60 years. Participants were randomly assigned to receive routine care (control, n = 48), to the self-monitored blood glucose (SMBG, n = 47) group, or to the u-healthcare group (n = 49). The primary end point was the proportion of patients achieving A1C healthcare system refers to an individualized medical service in which medical instructions are given through the patient's mobile phone. Patients receive a glucometer with a public switched telephone network-connected cradle that automatically transfers test results to a hospital-based server. Once the data are transferred to the server, an automated system, the CDSS rule engine, generates and sends patient-specific messages by mobile phone. After 6 months of follow-up, the mean A1C level was significantly decreased from 7.8 ± 1.3% to 7.4 ± 1.0% (P healthcare group and from 7.9 ± 1.0% to 7.7 ± 1.0% (P = 0.020) in the SMBG group, compared with 7.9 ± 0.8% to 7.8 ± 1.0% (P = 0.274) in the control group. The proportion of patients with A1C healthcare group, 23.4% in the SMBG group (23.4%), and 14.0% in the control group (P healthcare service achieved better glycemic control with less hypoglycemia than SMBG and routine care and may provide effective and safe diabetes management in the elderly diabetic patients.

Hypoglycemia in a dog with a leiomyoma of the gastric wall producing an insulin-like growth factor II-like peptide.

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Boari, A; Barreca, A; Bestetti, G E; Minuto, F; Venturoli, M

1995-06-01

A 12-year-old mixed-breed male dog was referred to the Clinica Medica Veterinaria of Bologna University for recurrent episodes of seizures due to hypoglycemia with abnormally low plasma insulin levels (18 pmol/l). Resection of a large leiomyoma (780 g) of the gastric wall resulted in a permanent resolution of the hypoglycemic episodes. Insulin-like growth factors I and II (IGF-I and -II) were measured by RIA in serum before and after surgery and in tumor tissue. Results were compared to the serum concentration of 54 normal and to the tissue concentration observed in eight non-hypoglycemic dog gastric wall extracts. Before surgery, circulating immunoreactive IGF-I was 0.92 nmol/l, which is significantly lower than the control values (16.92 +/- 8.44 nmol/l, range 3.53-35.03), while IGF-II was 152 nmol/l, which is significantly higher than the control values (42.21 +/- 3.75, range 31.99-50.74). After surgery, IGF-I increased to 6.80 nmol/l while IGF-II decreased to 45.52 nmol/l. Tumor tissue IGF-II concentration was higher than normal (5.66 nmol/kg tissue as compared to a range in normal gastric wall tissue of 1.14-3.72 nmol/kg), while IGF-I was 0.08 nmol/kg tissue, which is close to the lowest normal value (range in controls, 0.08-1.18 nmol/kg). Partial characterization of IGF-II immunoreactivity extracted from tissue evidenced a molecular weight similar to that of mature IGF-II, thus excluding that peptide released by the tumor is a precursor molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Vildagliptin added to sulfonylurea improves glycemic control without hypoglycemia and weight gain in Chinese patients with type 2 diabetes mellitus.

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Yang, Wenying; Xing, Xiaoping; Lv, Xiaofeng; Li, Yiming; Ma, Jianhua; Yuan, Guoyue; Sun, Feifei; Wang, Wei; Woloschak, Michael; Lukashevich, Valentina; Kozlovski, Plamen; Kothny, Wolfgang

2015-03-01

The aim of the present study was to assess the efficacy and safety of vildagliptin as add-on to sulfonylurea therapy in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on sulfonylurea monotherapy. The 24-week randomized double-blind placebo-controlled study compared vildagliptin 50 mg, q.d., with placebo as add-on to glimepiride in T2DM patients who were inadequately controlled (HbA1c 7.5%-11.0% [58-97 mmol/mol]) on a stable dose of sulfonylurea for ≥12 weeks before study entry. In all, 279 patients were randomized to receive either vildagliptin (n = 143) or placebo (n = 136). At baseline, overall mean age was 58.5 years, body weight 68.1 kg, duration of diabetes 6.9 years and daily glimepiride dose 3.3 mg. After 24 weeks, the adjusted mean change (AMΔ) in HbA1c was -0.7% (-8 mmol/mol; baseline 8.6%, 70 mmol/mol) in the vildagliptin group and -0.2% (-2 mmol/mol; baseline 8.7%, 72 mmol/mol) in the placebo group, with a treatment difference of -0.5% (-5 mmol/mol; P vildagliptin and placebo groups reported low and comparable incidences of adverse events (14.0% vs. 17.8%) and serious adverse events (0.7% in each group). Vildagliptin 50 mg, q.d., added to sulfonylurea monotherapy is effective in Chinese patients with T2DM, without increasing the risk of hypoglycemia and weight gain. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Potassium channels as drugs targets in therapy of cardiovascular diseases: 25 years later

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Protić Dragana

2013-03-01

Full Text Available Potassium channels are the most variable ion channel group. They participate in numerous cardiovascular functions, for example regulation of vascular tone, maintenance of resting cardiac membrane potential and excitability of cardiac conduction tissue. Both drugs and endogenous ligands could modulate potassium channel function, belonging to the potassium channel blockers or openers. Modulation of potassium channels could be a therapeutic or adverse drug action. Class III antiarrhythmic agents block the potassium channels, thereby prolonging repolarization phase of action potential with resulting prolongation of effective refractory period. Their effectiveness against supraventricular and ventricular arrhythmias should be weighted against their proarrhythmogenic potential. In addition, numerous other antiarrhythmic agents could modulate potassium channels as well. Diazoxide, minoxidil and nicorandil (well known arterial vasodilators, as well as numerous newly synthesized substances with still unknown therapeutic potential, belong to the potassium channel activators/openers. Therapeutic use of such vasodilators may involve treatment of hypertension (diazoxide, minoxidil and stable angina (nicorandil. Their use might be accompanied with side effects, such as vasodilation, edema, hypotension and reflex tachycardia. Potassium channel openers have also an important role in the treatment of peripheral vascular disease and pulmonary hypertension. In the future, drugs with selective effects on the vascular or cardiac potassium channels could be useful therapeutic agents.

POTASSIUM CHANNELS AS DRUGS TARGETS IN THERAPY OF CARDIOVASCULAR DESEASES: 25 YEARS LATER

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Protić Dragana

2013-01-01

Full Text Available Potassium channels are the most variable ion channel group. They participate in numerous cardiovascular functions, for example regulation of vascular tone, maintenance of resting cardiac membrane potential and excitability of cardiac conduction tissue. Both drugs and endogenous ligands could modulate potassium channel function, belonging to the potassium channel blockers or openers. Modulation of potassium channels could be a therapeutic or adverse drug action. Class III antiarrhythmic agents block the potassium channels, thereby prolonging repolarization phase of action potential with resulting prolongation of effective refractory period. Their effectiveness against supraventricular and ventricular arrhythmias should be weighted against their proarrhythmogenic potential. In addition, numerous other antiarrhythmic agents could modulate potassium channels as well. Diazoxide, minoxidil and nicorandil (well known arterial vasodilators, as well as numerous newly synthesized substances with still unknown therapeutic potential, belong to the potassium channel activators/ openers. Therapeutic use of such vasodilators may involve treatment of hypertension (diazoxide, minoxidil and stable angina (nicorandil. Their use might be accompanied with side effects, such as vasodilation, edema, hypotension and reflex tachycardia. Potassium channel openers have also an important role in the treatment of peripheral vascular disease and pulmonary hypertension. In the future, drugs with selective effects on the vascular or cardiac potassium channels could be useful therapeutic agents.

A novel technique of Roux-en-Y gastric bypass reversal for postprandial hyperinsulinemic hypoglycaemia: A case report

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E. Qvigstad

2016-01-01

Conclusions: Reduction of plasma–glucose, insulin and GLP-1 excursions and symptoms were seen after gastric tube placement and partial RYGB reversal. This attenuation of GLP-1 response to feeding could reflect an adaptation to nutrients.

Transformation of Nonfunctioning Pancreatic Neuroendocrine Carcinoma Cells into Insulin Producing Cells after Treatment with Sunitinib

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Jung Hun Ohn

2013-06-01

Full Text Available We report a rare case of severe hypoglycemia after sunitinib treatment for pancreatic neuroendocrine carcinoma. We describe the initial clinical presentation, laboratory results, pathologic findings, and managment in a patient with a nonfunctioning pancreatic neuroendocrine carcinoma with liver metastases who developed life threatening hypoglycemia after 2 months of sunitinib therapy. A 46-year-old woman presented to the emergency department with loss of consciousness from hypoglycemia. Serum C-peptide and insulin levels at fasting state revealed that the hypoglycemia resulted from endogenous hyperinsulinemia. She had been diagnosed with nonfunctioning pancreatic neuroendocrine carcinoma based on a biopsy of metastatic cervical lymph node and was being treated with sunitinib, a small molecule tyrosine kinase inhibitor. Immunohistochemical stain of the metastatic liver mass demonstrated that the initially nonfunctioning neuroendocrine carcinoma cells had changed into insulin-producing cells after sunitinib therapy. Transarterial chemoembolization of the liver masses and systemic chemotherapy with streptozotocin/adriamycin relieved the hypoglycemia. A nonfunctioning pancreatic neuroendocrine carcinoma was transformed into an insulin-producing tumor after treatment with sunitinib, causing endogenous hyperinsulinemia and severe hypoglycemia.

Relationship of oxidative stress in skeletal muscle with obesity and obesity-associated hyperinsulinemia in horses.

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Banse, Heidi E; Frank, Nicholas; Kwong, Grace P S; McFarlane, Dianne

2015-10-01

In horses, hyperinsulinemia and insulin resistance (insulin dysregulation) are associated with the development of laminitis. Although obesity is associated with insulin dysregulation, the mechanism of obesity-associated insulin dysregulation remains to be established. We hypothesized that oxidative stress in skeletal muscle is associated with obesity-associated hyperinsulinemia in horses. Thirty-five light breed horses with body condition scores (BCS) of 3/9 to 9/9 were studied, including 7 obese, normoinsulinemic (BCS ≥ 7, resting serum insulin obese, hyperinsulinemic (resting serum insulin ≥ 30 μIU/mL) horses. Markers of oxidative stress (oxidative damage, mitochondrial function, and antioxidant capacity) were evaluated in skeletal muscle biopsies. A Spearman's rank correlation coefficient was used to determine relationships between markers of oxidative stress and BCS. Furthermore, to assess the role of oxidative stress in obesity-related hyperinsulinemia, markers of antioxidant capacity and oxidative damage were compared among lean, normoinsulinemic (L-NI); obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses. Increasing BCS was associated with an increase in gene expression of a mitochondrial protein responsible for mitochondrial biogenesis (estrogen-related receptor alpha, ERRα) and with increased antioxidant enzyme total superoxide dismutase (TotSOD) activity. When groups (L-NI, O-NI, and O-HI) were compared, TotSOD activity was increased and protein carbonyls, a marker of oxidative damage, decreased in the O-HI compared to the L-NI horses. These findings suggest that a protective antioxidant response occurred in the muscle of obese animals and that obesity-associated oxidative damage in skeletal muscle is not central to the pathogenesis of equine hyperinsulinemia.

Intact pituitary function is decisive for the catabolic response to TNF-α: studies of protein, glucose and fatty acid metabolism in hypopituitary and healthy subjects.

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Bach, Ermina; Møller, Andreas B; Jørgensen, Jens O L; Vendelbo, Mikkel H; Jessen, Niels; Olesen, Jonas F; Pedersen, Steen B; Nielsen, Thomas S; Møller, Niels

2015-02-01

TNF-α generates inflammatory responses and insulin resistance, lipolysis, and protein breakdown. It is unclear whether these changes depend on intact hypothalamo-pituitary stress hormone responses to trigger the release of cortisol and growth hormone. To define differential effects of TNF-α on glucose, protein, and lipid metabolism in hypopituitary patients (without intact hypothalamo-pituitary axis) and healthy controls. Randomized, placebo controlled, single-blinded. Setting, Participants, and Intervention: We studied eight hypopituitary (HP) patients and eight matched control subjects [control volunteers (CTR)] twice during 4-h basal and 2-h hyperinsulinemic clamp conditions with isotope dilution during infusion of saline or TNF-α(12 ng/kg/h) for 6 h. Phenylalanine, urea, palmitate, and glucose fluxes and fat biopsies in basal and clamp periods. TNF-α infusion significantly increased cortisol and GH levels in CTR but not in HP. TNF-α increased phenylalanine fluxes in both groups, with the increase being significantly greater in CTR, and raised urea flux by 40 % in CTR without any alteration in HP. Endogenous glucose production (EGP) was elevated in CTR compared to HP after TNF-α administration, whereas insulin sensitivity remained similarly unaffected in both groups. TNF-α increased whole body palmitate fluxes and decreased palmitate specific activity in CTR, but not in HP without statistical difference between groups. We did not detect significant effects TNF-α on lipase expression or regulation in fat. TNF-α increased both urea and amino acid fluxes and EGP significantly more in CTR compared to HP, suggesting that increases in endogenous cortisol and GH release are significant components of the metabolic response to TNF-α.

Effect of antioxidant supplementation on insulin sensitivity in response to endurance exercise training

DEFF Research Database (Denmark)

Yfanti, Christina; Nielsen, Anders R; Åkerström, Thorbjörn

2011-01-01

While production of reactive oxygen and nitrogen species (RONS) is associated with some of the beneficial adaptations to regular physical exercise, it is not established whether RONS play a role in the improved insulin-stimulated glucose uptake in skeletal muscle obtained by endurance training....... To assess the effect of antioxidant supplementation during endurance training on insulin-stimulated glucose uptake, twenty-one young healthy (age 29±1 y; BMI 25±3 Kg m(-2)) men were randomly assigned into either an antioxidant (AO; 500 mg vitamin C and 400 IU vitamin E (a-tocopherol) daily) or a placebo (PL......) group that both underwent a supervised intense endurance-training program, 5 times per week for 12 weeks. A 3-hour euglycemic-hyperinsulinemic clamp, a maximal oxygen consumption (VO(2max)) and maximal power output (P(max)) test, and body composition measurements (fat mass, fat-free mass) were performed...

Association of Neonatal Glycemia With Neurodevelopmental Outcomes at 4.5 Years.

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McKinlay, Christopher J D; Alsweiler, Jane M; Anstice, Nicola S; Burakevych, Nataliia; Chakraborty, Arijit; Chase, J Geoffrey; Gamble, Gregory D; Harris, Deborah L; Jacobs, Robert J; Jiang, Yannan; Paudel, Nabin; San Diego, Ryan J; Thompson, Benjamin; Wouldes, Trecia A; Harding, Jane E

2017-10-01

Hypoglycemia is common during neonatal transition and may cause permanent neurological impairment, but optimal intervention thresholds are unknown. To test the hypothesis that neurodevelopment at 4.5 years is related to the severity and frequency of neonatal hypoglycemia. The Children With Hypoglycemia and Their Later Development (CHYLD) Study is a prospective cohort investigation of moderate to late preterm and term infants born at risk of hypoglycemia. Clinicians were masked to neonatal interstitial glucose concentrations; outcome assessors were masked to neonatal glycemic status. The setting was a regional perinatal center in Hamilton, New Zealand. The study was conducted from December 2006 to November 2010. The dates of the follow-up were September 2011 to June 2015. Participants were 614 neonates born from 32 weeks' gestation with at least 1 risk factor for hypoglycemia, including diabetic mother, preterm, small, large, or acute illness. Blood and masked interstitial glucose concentrations were measured for up to 7 days after birth. Infants with hypoglycemia (whole-blood glucose concentration Neonatal hypoglycemic episode, defined as at least 1 consecutive blood glucose concentration less than 47 mg/dL, a severe episode (neonatal hypoglycemia (280 [58.7%]) did not have increased risk of neurosensory impairment (risk difference [RD], 0.01; 95% CI, -0.07 to 0.10 and risk ratio [RR], 0.96; 95% CI, 0.77 to 1.21). However, hypoglycemia was associated with increased risk of low executive function (RD, 0.05; 95% CI, 0.01 to 0.10 and RR, 2.32; 95% CI, 1.17 to 4.59) and visual motor function (RD, 0.03; 95% CI, 0.01 to 0.06 and RR, 3.67; 95% CI, 1.15 to 11.69), with highest risk in children exposed to severe, recurrent, or clinically undetected (interstitial episodes only) hypoglycemia. Neonatal hypoglycemia was not associated with increased risk of combined neurosensory impairment at 4.5 years but was associated with a dose-dependent increased risk of poor executive

Continuous Glucose Monitoring in Newborn Infants

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Thomas, Felicity; Signal, Mathew; Harris, Deborah L.; Weston, Philip J.; Harding, Jane E.; Shaw, Geoffrey M.

2014-01-01

Neonatal hypoglycemia is common and can cause serious brain injury. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing blood glucose (BG) measurements. Calibration algorithms use BG measurements to convert sensor signals into CGM data. Thus, inaccuracies in calibration BG measurements directly affect CGM values and any metrics calculated from them. The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia metrics in newborn infants. Data from 155 babies were used. Two timing and 3 BG meter error models (Abbott Optium Xceed, Roche Accu-Chek Inform II, Nova Statstrip) were created using empirical data. Monte-Carlo methods were employed, and each simulation was run 1000 times. Each set of patient data in each simulation had randomly selected timing and/or measurement error added to BG measurements before CGM data were calibrated. The number of hypoglycemic events, duration of hypoglycemia, and hypoglycemic index were then calculated using the CGM data and compared to baseline values. Timing error alone had little effect on hypoglycemia metrics, but measurement error caused substantial variation. Abbott results underreported the number of hypoglycemic events by up to 8 and Roche overreported by up to 4 where the original number reported was 2. Nova results were closest to baseline. Similar trends were observed in the other hypoglycemia metrics. Errors in blood glucose concentration measurements used for calibration of CGM devices can have a clinically important impact on detection of hypoglycemia. If CGM devices are going to be used for assessing hypoglycemia it is important to understand of the impact of these errors on CGM data. PMID:24876618

Who Should Be Considered for Islet Transplantation Alone?

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Othonos, Nantia; Choudhary, Pratik

2017-04-01

Episodic hypoglycemia is an almost inevitable consequence of exogenous insulin treatment of type 1 diabetes, and in up to 30% of patients, this can lead to impaired awareness of hypoglycemia. This predisposes to recurrent severe hypoglycemia and has a huge impact on quality of life. Although many patients can get resolution of severe hypoglycemia through novel education and technology, some patients continue to have ongoing life-threatening hypoglycemia. Islet transplantation offers an alternative therapeutic option for these patients, in whom these conventional approaches have been unsuccessful. This review discusses the selection process of identifying suitable candidates based on recent clinical data. Results from studies of islet transplantation suggest the optimal recipient characteristics for successful islet transplantation include age >35 years, insulin requirements 85 kg. Islet transplantation can completely resolve hypoglycemia and near-normalize glucose levels, achieving insulin independence for a limited period of time in up to 40% of patients. The selection of appropriate candidates, optimizing donor selection, the use of an optimized protocol for islet cell extraction, and immunosuppression therapy have been proved to be the key criteria for a favorable outcome in islet transplantation.

Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle.

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Santiago, Ammy M; Clegg, Deborah J; Routh, Vanessa H

2016-12-01

17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17βE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL-VMN glucose-sensing neurons (GSNs). These hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17βE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed. The response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5mM also peaked during diestrous; an effect which was blunted by the addition of 17βE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17βE application. These data suggest that physiological

Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle

Science.gov (United States)

Santiago, Ammy M.; Clegg, Deborah J.; Routh, Vanessa H.

2016-01-01

Objective 17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17βE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL-VMN glucose-sensing neurons (GSNs). Methods These hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17βE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed. Results The response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5mM also peaked during diestrous; an effect which was blunted by the addition of 17βE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17βE application. Conclusion

Insulin secretion after short- and long-term low-grade free fatty acid infusion in men with increased risk of developing type 2 diabetes

DEFF Research Database (Denmark)

Storgaard, Heidi; Jensen, Christine B; Vaag, Allan A

2003-01-01

We studied the effect of a low-grade short- and long-term 20% Intralipid infusion (0.4 mL(-1) x kg(-1) x h(-1)) on insulin secretion and insulin action in 15 elderly obese men; 7 glucose intolerant first-degree relatives of type 2 diabetic patients (impaired glucose tolerance [IGT] relatives) and 8...... healthy controls of similar age and body mass index (BMI). Intravenous glucose tolerance test (IVGTT) and a graded glucose infusion (dose-response test [DORE]) were performed to determine first phase insulin response and to explore the dose response relationship between glucose concentration and insulin...... secretion rates (ISR). ISR were calculated by deconvolution of plasma C-peptide concentrations. Insulin action was determined by performing a 120-minute hyperinsulinemic euglycemic clamp. All tests were performed 3 times, preceded by 0, 2, or 24 hours Intralipid infusion. Disposition indices (DI) were...

Growth hormone and insulin-like growth factor-1 concentrations in women with fibromyalgia.

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McCall-Hosenfeld, Jennifer S; Goldenberg, Don L; Hurwitz, Shelley; Adler, Gail K

2003-04-01

To determine activity of the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis in women with fibromyalgia (FM). Premenopausal women with FM (n = 24) and premenopausal healthy women (n = 27) were studied. IGF-1 was measured in 23 patients with FM and 25 controls. GH was measured during a stepped hypoglycemic hyperinsulinemic clamp procedure (blood glucose decreased from 90 to 40 mg/dl every 30 min in 10 mg/dl decrements) in 12 FM and 13 control subjects. IGF-1 concentrations were similar in the FM (200 +/- 71 ng/ml, mean +/- SD) and control (184 +/- 70 ng/ml) groups. By multiple variable analysis, IGF-1 was negatively associated with age (p = 0.0006), body mass index (BMI) (p = 0.006), and 24 h urinary free cortisol (p = 0.007) in healthy controls. Even after accounting for these factors, there was no association between FM and IGF-1. The average peak GH achieved during hypoglycemia was lower in patients with FM (range 5 to 58 ng/ml, median 13 ng/ml) versus controls (6 to 68 ng/ml, median 21 ng/ml) (p = 0.04). However, BMI was a significant predictor of average peak GH in FM (r = -0.62, p BMI, there was no significant association between FM subjects and the average peak GH (p = 0.20). In this sample of premenopausal women with FM, the activity of the GH-IGF-1 axis was similar to that of healthy controls. Increases in age and obesity were both strongly associated with lower activity of this axis, suggesting that these factors must be considered when studying activity of the GH-IGF-1 axis in FM.

Sildenafil protects neuronal cells from mitochondrial toxicity induced by β-amyloid peptide via ATP-sensitive K+ channels.

Science.gov (United States)

Son, Yonghae; Kim, Koanhoi; Cho, Hyok-Rae

2018-06-02

To understand the molecular mechanisms underlying the beneficial effects of sildenafil in animal models of neurological disorders, we investigated the effects of sildenafil on the mitochondrial toxicity induced by β-amyloid (Aβ) peptide. Treatment of HT-22 hippocampal neuronal cells with Aβ 25∼35 results in increased mitochondrial Ca 2+ load, which is subsequently suppressed by sildenafil as well as by diazoxide, a selective opener of the ATP-sensitive K + channels (K ATP ). However, the suppressive effects of sildenafil and diazoxide are significantly attenuated by 5-hydroxydecanoic acid (5-HD), a K ATP inhibitor. The increased mitochondrial Ca 2+ overload is accompanied by decrease in the intracellular ATP concentration, increase in intracellular ROS generation, occurrence of mitochondrial permeability transition, and activation of caspase-9 and cell death. Exposure to sildenafil inhibited the mitochondria-associated changes and cell death induced by Aβ. However, the inhibitory effects of sildenafil are abolished or weakened in the presence of 5-HD, suggesting that opening of the mitochondrial K ATP is required for sildenafil to exert these effects. Taken together, these results indicate that at the mitochondrial levels, sildenafil plays a protective role towards neuronal cell in an environment rich in Aβ, and exerts its effects via the mitochondrial K ATP channels-dependent mechanisms. Copyright © 2018 Elsevier Inc. All rights reserved.

Hypoglycaemia in anesthesiology practice: Diagnostic, preventive, and management strategies

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Sanjay Kalra

2013-01-01

Full Text Available Diabetes mellitus has emerged as one of the fastest growing non communicable diseases worldwide. Management of diabetic patients during surgical and critically illness is of paramount challenge to anesthesiologist and intensivist. Among its major acute complications, hypoglycemia has been given lesser attention as compared to other major acute complications; diabetic ketoacidosis and hyperosmolar non ketotic coma. However, newer studies and literary evidence have established the serious concerns of morbidity and mortality, both long- and short-term, related to hypoglycemia. basis. Invariably, diabetic patients are encountered in our daily routine practice of anesthesia. During fasting status as well as the perioperative period, it is hypoglycemia that is of high concern to anesthesiologist. Management has to be based on clinical, pharmacological, social, and psychological basis, so as to completely prevent the complications arising from an acute episode of hypoglycemia. This review aims to highlight various aspects of hypoglycemia and its management both from endocrine and anesthesia perspective.