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Sample records for intermediate insulin-induced hypoglycemia

  1. Norepinephrine kinetics during insulin-induced hypoglycemia

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    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...

  2. Renal lactate metabolism and gluconeogenesis during insulin-induced hypoglycemia.

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    Cersosimo, E; Molina, P E; Abumrad, N N

    1998-07-01

    The contribution of gluconeogenic precursors to renal glucose production (RGP) during insulin-induced hypoglycemia was assessed in conscious dogs. Ten days after surgical placement of sampling catheters in the right and left renal veins and femoral artery and an infusion catheter in the left renal artery, systemic and renal glucose and glycerol kinetics were measured with peripheral infusions of [6-3H]glucose and [2-13C]glycerol. Renal blood flow was determined with a flowprobe, and the renal balance of lactate, alanine, and glycerol was calculated by arteriovenous difference. After baseline, six dogs received 2-h simultaneous infusions of peripheral insulin (4 mU x kg(-1) x min(-1)) and left intrarenal [6,6-2H]dextrose (14 micromol x kg(-1) x min(-1)) to achieve and maintain left renal normoglycemia during systemic hypoglycemia. Arterial glucose decreased from 5.3 +/- 0.1 to 2.2 +/- 0.1 mmol/l; insulin increased from 46 +/- 5 to 1,050 +/- 50 pmol/l; epinephrine, from 130 +/- 8 to 1,825 +/- 50 pg/ml; norepinephrine, from 129 +/- 6 to 387 +/- 15 pg/ml; and glucagon, from 52 +/- 2 to 156 +/- 12 pg/ml (all P gluconeogenesis induced by hypoglycemia.

  3. 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.

  4. Paradoxical increase in liver ketogenesis during long-term insulin-induced hypoglycemia in diabetic rats.

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    Schiavon, Fabiana P M; Gazola, Vilma A F G; Furlan, Maria M D P; Barrena, Helenton C; Bazotte, Roberto B

    2011-02-01

    It is well established that insulin inhibits liver ketogenesis. However, during insulin-induced hypoglycemia (IIH) the release of counterregulatory hormones could overcome the insulin effect on ketogenesis. To clarify this question the ketogenic activity in livers from alloxan-diabetic rats submitted to long-term IIH was investigated. Moreover, liver glycogenolysis, gluconeogensis, ureagenesis and the production of L-lactate were measured, and its correlation with blood levels of ketone bodies (KB), L-lactate, glucose, urea and ammonia was investigated. For this purpose, overnight fasted alloxan-diabetic rats (DBT group) were compared with control non-diabetic rats (NDBT group). Long-term IIH was obtained with an intraperitoneal injection of Detemir insulin (1 U/kg), and KB, glucose, L-lactate, ammonia and urea were evaluated at 0, 2, 4, 6, 8 or 10 h after insulin injection. Because IIH was well established two hours after insulin injection this time was used for liver perfusion experiments. The administration of Detemir insulin decreased (P < 0.05) blood KB and glucose levels, but there was an increase in the blood L-lactate levels and a rebound increase in blood KB during the glucose recovery phase of IIH. In agreement with these results, the capacity to produce KB from octanoate was increased in the livers of DBT rats. Moreover, the elevated blood L-lactate levels in DBT rats could be attributed to the higher (P < 0.05) glycogenolysis when part of glucose from glycogenolysis enters glycolysis, producing L-lactate. In contrast, except glycerol, gluconeogenesis was negligible in the livers of DBT rats. Therefore, during long-term IIH the higher liver ketogenic capacity of DBT rats increased the risk of hyperketonemia. In addition, in spite of the fact that the insulin injection decreased blood KB, there was a risk of worsening lactic acidosis.

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

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    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 anesthetize...

  6. Ketogenesis evaluation in perfused liver of diabetic rats submitted to short-term insulin-induced hypoglycemia.

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    Barrena, Helenton Cristhian; Gazola, Vilma Aparecida Ferreira Godoi; Furlan, Maria Montserrat Diaz Pedrosa; Garcia, Rosângela Fernandes; de Souza, Helenir Medri; Bazotte, Roberto Barbosa

    2009-08-01

    Ketogenesis, inferred by the production of acetoacetate plus ss-hydroxybutyrate, in isolated perfused livers from 24-h fasted diabetic rats submitted to short-term insulin-induced hypoglycemia (IIH) was investigated. For this purpose, alloxan-diabetic rats that received intraperitoneal regular insulin (IIH group) or saline (COG group) injection were compared. An additional group of diabetic rats which received oral glucose (gavage) (100 mg kg(-1)) 15 min after insulin administration (IIH + glucose group) was included. The studies were performed 30 min after insulin (1.0 U kg(-1)) or saline injection. The ketogenesis before octanoate infusion was diminished (p ketogenesis, livers from diabetic rats submitted to short-term IIH which received insulin or insulin plus glucose showed maintained capacity to produce acetoacetate and ss-hydroxybutyrate from octanoate. (c) 2009 John Wiley & Sons, Ltd.

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

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    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...

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

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    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....

  9. Paradoxical insulin-induced increase in gluconeogenesis in response to prolonged hypoglycemia in conscious dogs.

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    Davis, S N; Dobbins, R; Tarumi, C; Jacobs, J; Neal, D; Cherrington, A D

    1995-03-01

    The aim of this study was to determine the effects of differing insulin concentrations on the gluconeogenic response to equivalent prolonged hypoglycemia. Insulin was infused intraportally, for 3 h, into normal 18-h fasted conscious dogs at 2 (lower, n = 6) or 8 mU.kg-1.min-1 (high, n = 7) on separate occasions. This resulted in steady-state arterial insulin levels of 80 +/- 8 and 610 +/- 55 microU/ml, respectively. Glucose was infused during high dose to maintain the hypoglycemic plateau (50 +/- 1 mg/dl) equivalent to lower. Epinephrine (806 +/- 180 vs. 2,589 +/- 260 pg/ml), norepinephrine (303 +/- 55 vs. 535 +/- 60 pg/ml), cortisol (5.8 +/- 1.2 vs. 12.1 +/- 1.5 micrograms/dl), and pancreatic polypeptide (598 +/- 250 vs. 1,198 +/- 150 pg/ml) were all increased (P gluconeogenesis accounted for between 42 and 100% of glucose production during high-dose infusion but only 22-52% during lower-dose insulin. Intrahepatic gluconeogenic efficiency, however, increased similarly during both protocols. Lipolysis, as indicated by arterial blood glycerol levels, increased by a greater amount during high- compared with lower-dose insulin infusion. Six hyperinsulinemic euglycemic control experiments (2 or 8 mU.kg-1.min-1, n = 3 in each) provided baseline data. Gluconeogenesis remained similar to basal levels, but lipolysis was significantly suppressed during both series of hyperinsulinemic euglycemic studies. In summary, these data suggest that 1) the important counterregulatory processes of gluconeogenesis and lipolysis can be significantly increased during prolonged hypoglycemia despite an eightfold increase in circulating insulin levels and 2) the amplified gluconeogenic rate present during the hypoglycemic high-dose insulin infusions was caused by enhanced substrate delivery to the liver rather than an increase in intrahepatic gluconeogenic efficiency.

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

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    Mikines, K J; Kjær, Michael; Hagen, C

    1985-01-01

    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...... min)-1, mean and SE) and 8 physically trained (VO2max 65 +/- 4 ml X (kg X min)-1) subjects. In response to hypoglycemia, levels of beta-endorphin and prolactin immunoreactivity in serum increased similarly in trained (from 41 +/- 2 pg X ml-1 and 6 +/- 1 pg X ml-1 before hypoglycemia to 103 +/- 11 pg X...... to hypoglycemia neither in trained nor in untrained subjects. Finally, differences in beta-endorphin responses to exercise between trained and untrained subjects cannot be ascribed to differences in responsiveness to hypoglycemia....

  11. Time sequence of changes in the responsiveness of glycogen breakdown to adrenergic agonists in perfused liver of rats with insulin-induced hypoglycemia

    Directory of Open Access Journals (Sweden)

    M. Vardanega-Peicher

    2000-07-01

    Full Text Available The time-course changes of the responsiveness of glycogen breakdown to a- and ß-adrenergic agonists during insulin-induced hypoglycemia (IIH were investigated. Blood glucose levels were decreased prior to the alteration in the hepatic responsiveness to adrenergic agonists. The activation of hepatic glucose production and glycogenolysis by phenylephrine (2 µM and isoproterenol (20 µM was decreased in IIH. The changes in the responsiveness of glycogen catabolism were first observed for isoproterenol and later for phenylephrine. Hepatic ß-adrenergic receptors showed a higher degree of adrenergic desensitization than did a-receptors. Liver glycogen synthase activity, glycogen content and the catabolic effect of dibutyryl cyclic AMP (the ß-receptor second messenger were not affected by IIH.

  12. Insulin-induced hypoglycemia associations with gene expression changes in liver and hypothalamus of chickens from lines selected for low or high body weight.

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    Rice, Brittany B; Zhang, Wei; Bai, Shiping; Siegel, Paul B; Cline, Mark A; Gilbert, Elizabeth R

    2014-11-01

    Chickens selected for low (LWS) or high (HWS) body weight for more than 56 generations now have a 10-fold difference in body weight at 56 days of age and correlated responses in appetite and glucose regulation. The LWS chickens are lean and some are anorexic, while the HWS are compulsive feeders and have a different threshold sensitivity of food intake and blood glucose to both central and peripheral insulin, respectively. We previously demonstrated that at 90-days of age, insulin-induced hypoglycemia was associated with reduced glucose transporter expression in the liver of both lines, and differences in expression of neuropeptide Y (NPY) and NPY receptor sub-type genes between LWS and HWS in the hypothalamus. The objective of this study was to determine effects of insulin-induced hypoglycemia on gene expression in the hypothalamus and liver of early post-hatch LWS and HWS chicks. On day 5 post-hatch chicks from each line were fasted for 3h and injected intraperitoneally with insulin or vehicle. At 1h post-injection, chicks were euthanized, blood glucose was measured, and hypothalamus and liver were removed. Total RNA was isolated and real time PCR performed. Insulin injection was associated with a more pronounced reduction in blood glucose in HWS compared with LWS chicks (two-way interaction; Phypothalamus (Phypothalamus of HWS than LWS (Phypothalamus of both lines (P=0.02). In the liver of both lines, insulin treatment was associated with decreased (P=0.01) GLUT2 mRNA and increased (P=0.01) GLUT1 mRNA, compared to vehicle-treated chicks. Results suggest that NPY-associated factors and glucose transporters are differentially-expressed between LWS and HWS chickens and that HWS chicks display greater sensitivity to exogenous insulin during the early post-hatch period. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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    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...

  14. Neuroendocrine and sympathetic responses to an orexin receptor antagonist, SB-649868, and alprazolam following insulin-induced hypoglycemia in humans.

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    Patel, Ameera X; Miller, Sam R; Nathan, Pradeep J; Kanakaraj, Ponmani; Napolitano, Antonella; Lawrence, Philip; Koch, Annelize; Bullmore, Edward T

    2014-10-01

    The orexin-hypocretin system is important for translating peripheral metabolic signals and central neuronal inputs to a diverse range of behaviors, from feeding, motivation and arousal, to sleep and wakefulness. Orexin signaling is thus an exciting potential therapeutic target for disorders of sleep, feeding, addiction, and stress. Here, we investigated the low dose pharmacology of orexin receptor antagonist, SB-649868, on neuroendocrine, sympathetic nervous system, and behavioral responses to insulin-induced hypoglycemic stress, in 24 healthy male subjects (aged 18-45 years; BMI 19.0-25.9 kg/m(2)), using a randomized, double-blind, placebo-controlled, within-subject crossover design. Alprazolam, a licensed benzodiazepine anxiolytic, was used as a positive comparator, as it has previously been validated using the insulin tolerance test (ITT) model in humans. Of the primary endpoints, ITT induced defined increases in pulse rate, plasma cortisol, and adrenocorticotropic hormone in the placebo condition, but these responses were not significantly impacted by alprazolam or SB-649868 pre-treatment. Of the secondary endpoints, ITT induced a defined increase in plasma concentrations of adrenaline, noradrenaline, growth hormone (GH), and prolactin in the placebo condition. Alprazolam pre-treatment significantly reduced the GH response to ITT (p neuroendocrine or sympathetic nervous systems, but could not be validated for studying low dose orexin antagonist activity.

  15. 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

    -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...

  16. I.c.v. administration of the nonsteroidal glucocorticoid receptor antagonist, CP-472555, prevents exacerbated hypoglycemia during repeated insulin administration.

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    Kale, A Y; Paranjape, S A; Briski, K P

    2006-06-30

    Hypoglycemia elicits an integrated array of CNS-mediated counterregulatory responses, including activation of the hypothalamic-pituitary-adrenal axis. The role of antecedent adrenocortical hypersecretion in impaired glucose counterregulation remains controversial. The present studies utilized the selective, nonsteroidal glucocorticoid receptor antagonist, CP-472555, as a pharmacological tool to investigate the hypothesis that hypoglycemic hypercorticosteronemia modulates CNS efferent autonomic and neuroendocrine motor responses to recurring insulin-induced hypoglycemia via glucocorticoid receptor-dependent mechanisms. Groups of adult male rats were injected s.c. with either one or four doses of the intermediate-acting insulin, Humulin neutral protamine Hagedorn (NPH), on as many days, while controls were injected with diluent alone. Animals injected with four doses of insulin were pretreated by i.c.v. administration of graded doses of the glucocorticoid receptor antagonist or vehicle alone prior to the first three doses of insulin. Repeated daily injection of NPH exacerbated hypoglycemia, attenuated patterns of glucagon and epinephrine secretion, and diminished neuronal transcriptional activation in discrete CNS metabolic loci, including the lateral hypothalamic area, dorsomedial hypothalamic nucleus, paraventricular hypothalamic nucleus, and nucleus of the solitary tract. While i.c.v. delivery of 25 or 100 ng doses of CP-472555 did not alter any of these parameters, animals treated with 500 ng exhibited circulating glucose, glucagon, and epinephrine levels that were similar to those in rats injected with one dose of insulin, as well as a reversal of recurring insulin-induced hypoglycemia-associated reductions in Fos immunolabeling in the lateral hypothalamic area, dorsomedial hypothalamic nucleus, and paraventricular hypothalamic nucleus. These results provide unique pharmacological evidence that antecedent activation of central glucocorticoid receptor is required

  17. Effects of chemical sympathectomy on the increases in plasma catecholamines and dopamine-beta-hydroxylase induced by forced immobilization and insulin-induced hypoglycemia: origin and fate of plasma dopamine-beta-hydroxylase.

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    Israel, A S; Barbella, Y R; Cubeddu, L X

    1982-06-01

    The effect of acute stresses on plasma norepinephrine, epinephrine and dopamine-beta-hydroxylase (DBH) were evaluated in control and 6-hydroxydopamine-treated, awake cannulated guinea pigs. Forced immobolization for 1 hr caused a 3- and 5-fold increase in plasma DBH and norepinephrine, respectively. Pretreatment with 6-hydroxydopamine (23 mg/kg b.wt.i.a., 72 and 48 hr before stress) reduced by 70% the increase in plasma DBH and totally prevented the rise in plasma catecholamines evoked by the restraining stress. Injection of insulin (5 U/kg b.wt.i.a.) induced a 60% decrease in blood glucose, a 1-fold increase in plasma DBH and a selective 4-fold increase in plasma epinephrine; these effects were not modified by chemical sympathectomy. Our results indicate that forced immobilization and hypoglycemia produce a preferential activation of the sympathetic postganglionic nerves and of the adrenal medulla, respectively, and that in guinea pigs both stresses increase plasma DBH. The kinetics of disappearance of plasma DBH were studied after subjecting the guinea pigs for 1 hr to forced immobilization. Although 7 of 12 animals showed a biphasic rate of fall of plasma DBH, in each case there was a rapid initial fall possibly due to the "distribution" of the enzyme with a T1/2 of 1.65 hr. Similar findings were observed in 6-hydroxydopamine-treated guinea pigs. These results suggest that the distribution of DBH is the most important process in reducing the augmented plasma DBH levels elicited by a short-term stress and that this process is not dependent on the integrity of the sympathetic nerves nor on the adrenal or sympathetic origin of the enzyme. This study supports the view that the ratio, content of releasable DBH present in sympathetic nerves and adrenal glands/total circulating pool of DBH, is the factor that determines whether an increase in plasma DBH would occur in animals exposed to an acute stress.

  18. Sleep disturbances in IDDM patients with nocturnal hypoglycemia

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    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...

  19. 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 polygrap......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...

  20. 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

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

    DEFF Research Database (Denmark)

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

    1990-01-01

    )]. 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...

  2. No response of pancreatic hormones to hypoglycemia in diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Krarup, T

    1982-01-01

    The responses of pancreatic hormones (i.e. glucagon, pancreatic polypeptide, and somatostatin) to insulin-induced hypoglycemia were investigated in 18 insulin-dependent diabetics without residual beta-cell function and in 6 normal subjects. Nine of the diabetics had autonomic neuropathy, and 9 had...... no neuropathy. After hypoglycemia, no significant increase in any of the 3 pancreatic hormones was found in the diabetics with autonomic neuropathy, whereas significant increments were found in the diabetics without neuropathy and in the normal subjects. These results suggest that autonomic nervous activity...... is of major importance for pancreatic hormone release during hypoglycemia in man....

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

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

    1994-01-01

    after insulin-induced hypoglycemia. Eleven healthy subjects and nine type I (insulin-dependent) diabetic patients each participated in two experiments in randomized order, receiving on both days an insulin bolus of 0.15 IU/kg soluble insulin. On one day, theophylline (intravenous [IV] bolus of 220 mg...... 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...

  4. Low Blood Glucose (Hypoglycemia)

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    ... you up if you have hypoglycemia during sleep. Eat regular meals and snacks Your meal plan is key to preventing hypoglycemia. Eat regular meals and snacks with the correct amount of carbohydrates ...

  5. Detection of hypoglycemia associated EEG changes during sleep in type 1 diabetes mellitus.

    Science.gov (United States)

    Snogdal, Lena Sønder; Folkestad, Lars; Elsborg, Rasmus; Remvig, Line Sofie; Beck-Nielsen, Henning; Thorsteinsson, Birger; Jennum, Poul; Gjerstad, Michaela; Juhl, Claus B

    2012-10-01

    Nocturnal hypoglycemia is a feared complication to insulin treated diabetes. Impaired awareness of hypoglycemia (IAH) increases the risk of severe hypoglycemia. EEG changes are demonstrated during daytime hypoglycemia. In this explorative study, we test the hypothesis that specific hypoglycemia-associated EEG-changes occur during sleep and are detectable in time for the patient to take action. Ten patients with type 1 diabetes (duration 23.7 years) with IAH were exposed to insulin-induced hypoglycemia during the daytime and during sleep. EEG was recorded and analyzed real-time by an automated multi-parameter algorithm. Participants received an auditory alarm when EEG changes met a predefined threshold, and were instructed to consume a meal. Seven out of eight participants developed hypoglycemia-associated EEG changes during daytime. During sleep, nine out of ten developed EEG changes (mean BG 2.0 mmol/l). Eight were awakened by the alarm. Four corrected hypoglycemia (mean BG 2.2 mmol/l), while four (mean BG 1.9 mmol/l) received glucose infusion. Two had false alarms. EEG-changes occurred irrespective of sleep stage. Post hoc improvement indicates the possibility of earlier detection of hypoglycemia. Continuous EEG monitoring and automated real-time analysis may constitute a novel technique for a hypoglycemia alarm in patients with IAH. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. Glucose turnover and hormonal changes during insulin-induced hypoglycemia in trained humans

    DEFF Research Database (Denmark)

    Kjær, Michael; Mikines, K J; Christensen, N J

    1984-01-01

    Eight athletes (T), studied the third morning after the last exercise session, and seven sedentary males (C) (maximal O2 consumption 65 +/- 4 vs. 49 +/- 4 (SE) ml X kg-1 X min-1, for T and C men, respectively) had insulin infused until plasma glucose, at an insulin level of 1,600 pmol X l-1, was ...

  7. Insulin-Inducible SMILE Inhibits Hepatic Gluconeogenesis.

    Science.gov (United States)

    Lee, Ji-Min; Seo, Woo-Young; Han, Hye-Sook; Oh, Kyoung-Jin; Lee, Yong-Soo; Kim, Don-Kyu; Choi, Seri; Choi, Byeong Hun; Harris, Robert A; Lee, Chul-Ho; Koo, Seung-Hoi; Choi, Hueng-Sik

    2016-01-01

    The role of a glucagon/cAMP-dependent protein kinase-inducible coactivator PGC-1α signaling pathway is well characterized in hepatic gluconeogenesis. However, an opposing protein kinase B (PKB)/Akt-inducible corepressor signaling pathway is unknown. A previous report has demonstrated that small heterodimer partner-interacting leucine zipper protein (SMILE) regulates the nuclear receptors and transcriptional factors that control hepatic gluconeogenesis. Here, we show that hepatic SMILE expression was induced by feeding in normal mice but not in db/db and high-fat diet (HFD)-fed mice. Interestingly, SMILE expression was induced by insulin in mouse primary hepatocyte and liver. Hepatic SMILE expression was not altered by refeeding in liver-specific insulin receptor knockout (LIRKO) or PKB β-deficient (PKBβ(-/-)) mice. At the molecular level, SMILE inhibited hepatocyte nuclear factor 4-mediated transcriptional activity via direct competition with PGC-1α. Moreover, ablation of SMILE augmented gluconeogenesis and increased blood glucose levels in mice. Conversely, overexpression of SMILE reduced hepatic gluconeogenic gene expression and ameliorated hyperglycemia and glucose intolerance in db/db and HFD-fed mice. Therefore, SMILE is an insulin-inducible corepressor that suppresses hepatic gluconeogenesis. Small molecules that enhance SMILE expression would have potential for treating hyperglycemia in diabetes. © 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.

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

    DEFF Research Database (Denmark)

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

    1990-01-01

    Studies in humans have indicated that trained athletes compared with sedentary subjects have an increased capacity to secrete epinephrine. To investigate whether this is due to an adaptation induced by physical training or a selection phenomenon, rats were swim trained (T) 10 wk for 6 h/day or se...... nervous system to reduced blood glucose levels induced by repeated exercise bouts, the epinephrine response to insulin-induced hypoglycemia is markedly diminished after training.......)]. 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...... compared with trained rats. During hypoglycemia the epinephrine response was much smaller in trained than in untrained rats (P less than 0.05). In conclusion, in rats strenuous endurance training causes an enlargement of the adrenal medulla. However, possibly reflecting an adaptation within the central...

  9. Insulin induces calcium signals in the nucleus of rat hepatocytes.

    Science.gov (United States)

    Rodrigues, Michele A; Gomes, Dawidson A; Andrade, Viviane A; Leite, M Fatima; Nathanson, Michael H

    2008-11-01

    Insulin is an hepatic mitogen that promotes liver regeneration. Actions of insulin are mediated by the insulin receptor, which is a receptor tyrosine kinase. It is currently thought that signaling via the insulin receptor occurs at the plasma membrane, where it binds to insulin. Here we report that insulin induces calcium oscillations in isolated rat hepatocytes, and that these calcium signals depend upon activation of phospholipase C and the inositol 1,4,5-trisphosphate receptor, but not upon extracellular calcium. Furthermore, insulin-induced calcium signals occur in the nucleus, and are temporally associated with selective depletion of nuclear phosphatidylinositol bisphosphate and translocation of the insulin receptor to the nucleus. These findings suggest that the insulin receptor translocates to the nucleus to initiate nuclear, inositol 1,4,5-trisphosphate-mediated calcium signals in rat hepatocytes. This novel signaling mechanism may be responsible for insulin's effects on liver growth and regeneration.

  10. Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Yeom, Chul-gon; Kim, Dong-il; Park, Min-jung; Choi, Joo-hee [College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Jeong, Jieun; Wi, Anjin; Park, Whoashig [Jeollanamdo Forest Resources Research Institute, Naju 520-833 (Korea, Republic of); Han, Ho-jae [College of Veterinary Medicine, Seoul National University, Seoul 151-741 (Korea, Republic of); Park, Soo-hyun, E-mail: parksh@chonnam.ac.kr [College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 (Korea, Republic of)

    2015-06-05

    Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the ‘fed’ condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology. - Highlights: • Insulin treatment increases CARM1 expression in hepatocytes. • CARM1 overexpression does not increase the expression of lipogenic proteins. • CARM1 knockdown does not influence insulin sensitivity. • Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation.

  11. Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

    International Nuclear Information System (INIS)

    Yeom, Chul-gon; Kim, Dong-il; Park, Min-jung; Choi, Joo-hee; Jeong, Jieun; Wi, Anjin; Park, Whoashig; Han, Ho-jae; Park, Soo-hyun

    2015-01-01

    Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the ‘fed’ condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology. - Highlights: • Insulin treatment increases CARM1 expression in hepatocytes. • CARM1 overexpression does not increase the expression of lipogenic proteins. • CARM1 knockdown does not influence insulin sensitivity. • Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

  12. 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...

  13. Subcutaneous blood flow during insulin-induced hypoglycaemia

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Sestoft, L

    1982-01-01

    Subcutaneous blood flow was measured preceding insulin-induced hypoglycaemia, at the onset of hypoglycaemic symptoms and 2 h later in juvenile diabetics with and without autonomic neuropathy and in normal males. In all groups subcutaneous blood flow decreased at the onset of hypoglycaemic symptoms...... compared with pre-hypoglycaemic flow. Two hours after onset of hypoglycaemic symptoms, subcutaneous blood flow was still significantly decreased compared with pre-hypoglycaemic flow. In normal subjects local nerve blockade had no effect on blood flow changes during hypoglycaemia, whereas local alpha...

  14. Advanced glycation endproducts in horses with insulin-induced laminitis.

    Science.gov (United States)

    de Laat, M A; Kyaw-Tanner, M T; Sillence, M N; McGowan, C M; Pollitt, C C

    2012-01-15

    Advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of cancer, inflammatory conditions and diabetic complications. An interaction of AGEs with their receptor (RAGE) results in increased release of pro-inflammatory cytokines and reactive oxygen species (ROS), causing damage to susceptible tissues. Laminitis, a debilitating foot condition of horses, occurs in association with endocrine dysfunction and the potential involvement of AGE and RAGE in the pathogenesis of the disease has not been previously investigated. Glucose transport in lamellar tissue is thought to be largely insulin-independent (GLUT-1), which may make the lamellae susceptible to protein glycosylation and oxidative stress during periods of increased glucose metabolism. Archived lamellar tissue from horses with insulin-induced laminitis (n=4), normal control horses (n=4) and horses in the developmental stages (6h, 12h and 24h) of the disease (n=12) was assessed for AGE accumulation and the presence of oxidative protein damage and cellular lipid peroxidation. The equine-specific RAGE gene was identified in lamellar tissue, sequenced and is now available on GenBank. Lamellar glucose transporter (GLUT-1 and GLUT-4) gene expression was assessed quantitatively with qRT-PCR in laminitic and control horses and horses in the mid-developmental time-point (24 h) of the disease. Significant AGE accumulation had occurred by the onset of insulin-induced laminitis (48 h) but not at earlier time-points, or in control horses. Evidence of oxidative stress was not found in any group. The equine-specific RAGE gene was not expressed differently in treated and control animals, nor was the insulin-dependent glucose transporter GLUT-4. However, the glucose transporter GLUT-1 was increased in lamellar tissue in the developmental stages of insulin-induced laminitis compared to control horses and the insulin-independent nature of the lamellae may facilitate AGE formation. However, due to the lack of

  15. 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....

  16. Retrospective evaluation of a national guideline to prevent neonatal hypoglycemia

    Directory of Open Access Journals (Sweden)

    Annett Helleskov Rasmussen

    2017-10-01

    Conclusion: Stratification of hypoglycemia risk in a hypoglycemia prevention guideline was followed by decreased estimated hypoglycemia incidence, but no causative conclusion could be drawn. Prospective studies with risk stratification for hypoglycemia prevention are encouraged.

  17. Subcutaneous blood flow during insulin-induced hypoglycaemia

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Sestoft, L

    1982-01-01

    Subcutaneous blood flow was measured preceding insulin-induced hypoglycaemia, at the onset of hypoglycaemic symptoms and 2 h later in juvenile diabetics with and without autonomic neuropathy and in normal males. In all groups subcutaneous blood flow decreased at the onset of hypoglycaemic symptoms...... compared with pre-hypoglycaemic flow. Two hours after onset of hypoglycaemic symptoms, subcutaneous blood flow was still significantly decreased compared with pre-hypoglycaemic flow. In normal subjects local nerve blockade had no effect on blood flow changes during hypoglycaemia, whereas local alpha......-receptor blockade abolished the vasoconstrictor response. We suggest that circulating catecholamines stimulating vascular alpha-receptors are probably responsible for flow reduction in the subcutaneous tissue during hypoglycaemia....

  18. 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...

  19. The importance of hypoglycemia in diabetic patients

    Directory of Open Access Journals (Sweden)

    Shafiee Gita

    2012-10-01

    Full Text Available Abstract Hypoglycemia is one of the most important complications of diabetes treatment. The risk of severe hypoglycemia is higher in elderly patients, those having comorbidities such as vascular disease or renal failure, pregnant women and in children with type 1diabetes. Moreover, in type 2 diabetes, progressive insulin deficiency, longer duration of diabetes, and tight glycemic control increase the risk of hypoglycemia as much as type 1 diabetes.Episodes hypoglycemia may lead to impairment of counter-regulatory system, with the potential of development of hypoglycemia unawareness. So, hypoglycemia may increase the vascular events even death in addition to other possible detrimental effects. Glycemic control should be individualized based on patient characteristics with some degree of safety. Recognition of hypoglycemia risk factors, blood glucose monitoring, selection of appropriate regimens and educational programs for healthcare professionals and patients with diabetes are the major issues to maintain good glycemic control, minimize the risk of hypoglycemia, and prevent long- term complications.

  20. Paliperidone Induced Hypoglycemia by Increasing Insulin Secretion

    Directory of Open Access Journals (Sweden)

    Tsubasa Omi

    2016-01-01

    Full Text Available We report the case of a 41-year-old woman with schizophrenia who developed persistent hypoglycemia following paliperidone administration. After discontinuing paliperidone, the hypoglycemia resolved, but symptoms of diabetes emerged. Therefore, it appears that the hypoglycemia induced by paliperidone may mask symptoms of diabetes. Paliperidone may induce hypoglycemia by increasing insulin secretion. This report could help elucidate the relationship between atypical antipsychotics and glucose metabolism.

  1. Paliperidone Induced Hypoglycemia by Increasing Insulin Secretion

    OpenAIRE

    Omi, Tsubasa; Riku, Keisen; Fukumoto, Motoyuki; Kanai, Koji; Omura, Yumi; Takada, Hiromune; Matunaga, Hidenori

    2016-01-01

    We report the case of a 41-year-old woman with schizophrenia who developed persistent hypoglycemia following paliperidone administration. After discontinuing paliperidone, the hypoglycemia resolved, but symptoms of diabetes emerged. Therefore, it appears that the hypoglycemia induced by paliperidone may mask symptoms of diabetes. Paliperidone may induce hypoglycemia by increasing insulin secretion. This report could help elucidate the relationship between atypical antipsychotics and glucose m...

  2. 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...

  3. 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.

  4. Hypoglycemia-Associated EEG Changes Following Antecedent Hypoglycemia in Type 1 Diabetes Mellitus

    DEFF Research Database (Denmark)

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

    2017-01-01

    of hypoglycemia. METHODS: Twenty-four patients with type 1 diabetes mellitus (10 with normal hypoglycemia awareness, 14 with hypoglycemia unawareness) were studied on 2 consecutive days by hyperinsulinemic glucose clamp at hypoglycemia (2.0-2.5 mmol/L) during a 1-h period. EEG was recorded, cognitive function...... function between the two groups on day 2. The symptom response was higher in the aware group on both days, while only subtle differences were seen in the counterregulatory hormonal response. CONCLUSION: Antecedent hypoglycemia does not affect hypoglycemia-associated EEG changes in patients with type 1...... diabetes mellitus....

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

    DEFF Research Database (Denmark)

    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 type...... 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....

  6. Hypoglycemia

    Science.gov (United States)

    ... 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 ...

  7. Hypoglycemia

    Science.gov (United States)

    ... 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, ...

  8. Benign prostatic hyperplasia presenting with profound hypoglycemia

    African Journals Online (AJOL)

    Introduction: Approximately 90% of patients with diabetes have type 2 diabetes. Hypoglycemia ... Clinical case: We report the case of a man aged 85 years followed for type 2 diabetes and hypertension. ... Neurological disorders related to hypoglycemia were agitation, delirium, impaired higher functions and sleep disorders.

  9. Postprandial Hyperinsulinemic Hypoglycemia in Bariatric Surgery

    NARCIS (Netherlands)

    de Heide, L. J.M.; Emous, M.; van Beek, A. P.

    2016-01-01

    Postprandial hyperinsulinemic hypoglycemia (PHH) is a complication of bariatric surgery, especially Roux-en-Y gastric bypass. The true incidence is not known as the definition of PHH is not clear. Continuous glucose monitoring shows a prevalence of hypoglycemia in 75% of patients, with only 1 in 5

  10. A novel algorithm for prediction and detection of hypoglycemia based on continuous glucose monitoring and heart rate variability in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Cichosz, Simon Lebech; Frystyk, Jan; Hejlesen, Ole

    2014-01-01

    prior to each blood glucose sample were used to decide if that particular point in time was below the hypoglycemic threshold of 3.9 mmol/L. A total of 903 samples were analyzed by the novel algorithm, which yielded a sensitivity of 79% and a specificity of 99%. The algorithm was able to detect 16......, but with a modest accuracy. Therefore, our aim was to investigate whether a novel algorithm that adds information of the complex dynamic/pattern of heart rate variability (HRV) could improve the accuracy of hypoglycemia as detected by a CGM device. Data from 10 patients with type 1 diabetes studied during insulin......-induced hypoglycemia were obtained. Blood glucose samples were used as reference. HRV patterns and CGM data were combined in a mathematical prediction algorithm. Detection of hypoglycemic periods, performed by the algorithm, was treated as a pattern recognition problem and features/patterns derived from HRV and CGM...

  11. Cerebral blood flow response to hypoglycemia is altered in patients with type 1 diabetes and impaired awareness of hypoglycemia.

    Science.gov (United States)

    Wiegers, Evita C; Becker, Kirsten M; Rooijackers, Hanne M; von Samson-Himmelstjerna, Federico C; Tack, Cees J; Heerschap, Arend; de Galan, Bastiaan E; van der Graaf, Marinette

    2017-06-01

    It is unclear whether cerebral blood flow responses to hypoglycemia are altered in people with type 1 diabetes and impaired awareness of hypoglycemia. The aim of this study was to investigate the effect of hypoglycemia on both global and regional cerebral blood flow in type 1 diabetes patients with impaired awareness of hypoglycemia, type 1 diabetes patients with normal awareness of hypoglycemia and healthy controls ( n = 7 per group). The subjects underwent a hyperinsulinemic euglycemic-hypoglycemic glucose clamp in a 3 T MR system. Global and regional changes in cerebral blood flow were determined by arterial spin labeling magnetic resonance imaging, at the end of both glycemic phases. Hypoglycemia generated typical symptoms in patients with type 1 diabetes and normal awareness of hypoglycemia and healthy controls, but not in patients with impaired awareness of hypoglycemia. Conversely, hypoglycemia increased global cerebral blood flow in patients with impaired awareness of hypoglycemia, which was not observed in the other two groups. Regionally, hypoglycemia caused a redistribution of cerebral blood flow towards the thalamus of both patients with normal awareness of hypoglycemia and healthy controls, consistent with activation of brain regions associated with the autonomic response to hypoglycemia. No such redistribution was found in the patients with impaired awareness of hypoglycemia. An increase in global cerebral blood flow may enhance nutrient supply to the brain, hence suppressing symptomatic awareness of hypoglycemia. Altogether these results suggest that changes in cerebral blood flow during hypoglycemia contribute to impaired awareness of hypoglycemia.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Role of gluconeogenesis in sustaining glucose production during hypoglycemia caused by continuous insulin infusion in conscious dogs.

    Science.gov (United States)

    Frizzell, R T; Hendrick, G K; Biggers, D W; Lacy, D B; Donahue, D P; Green, D R; Carr, R K; Williams, P E; Stevenson, R W; Cherrington, A D

    1988-06-01

    The roles of glycogenolysis and gluconeogenesis in sustaining glucose production during insulin-induced hypoglycemia were assessed in overnight-fasted conscious dogs. Insulin was infused intraportally for 3 h at 5 mU.kg-1.min-1 in five animals, and glycogenolysis and gluconeogenesis were measured by using a combination of tracer [( 3-3H]glucose and [U-14C]alanine) and hepatic arteriovenous difference techniques. In response to the elevated insulin level (263 +/- 39 microU/ml), plasma glucose level fell (41 +/- 3 mg/dl), and levels of the counterregulatory hormones glucagon, epinephrine, norepinephrine, and cortisol increased (91 +/- 29 to 271 +/- 55 pg/ml, 83 +/- 26 to 2356 +/- 632 pg/ml, 128 +/- 31 to 596 +/- 81 pg/ml, and 1.5 +/- 0.4 to 11.1 +/- 1.0 micrograms/dl, respectively; for all, P less than .05). Glucose production fell initially and then doubled (3.1 +/- 0.3 to 6.1 +/- 0.5 mg.kg-1.min-1; P less than .05) by 60 min. Net hepatic gluconeogenic precursor uptake increased approximately eightfold by the end of the hypoglycemic period. By the same time, the efficiency with which the liver converted the gluconeogenic precursors to glucose rose twofold. Five control experiments in which euglycemia was maintained by glucose infusion during insulin administration (5.0 mU.kg-1.min-1) provided baseline data. Glycogenolysis accounted for 69-88% of glucose production during the 1st h of hypoglycemia, whereas gluconeogenesis accounted for 48-88% of glucose production during the 3rd h of hypoglycemia. These data suggest that gluconeogenesis is the key process for the normal counterregulatory response to prolonged and marked hypoglycemia.

  15. Glucose autoregulation is the dominant component of the hormone-independent counterregulatory response to hypoglycemia in the conscious dog.

    Science.gov (United States)

    Gregory, Justin M; Rivera, Noelia; Kraft, Guillaume; Winnick, Jason J; Farmer, Ben; Allen, Eric J; Donahue, E Patrick; Smith, Marta S; Edgerton, Dale S; Williams, Phillip E; Cherrington, Alan D

    2017-09-01

    The contribution of hormone-independent counterregulatory signals in defense of insulin-induced hypoglycemia was determined in adrenalectomized, overnight-fasted conscious dogs receiving hepatic portal vein insulin infusions at a rate 20-fold basal. Either euglycemia was maintained ( group 1 ) or hypoglycemia (≈45 mg/dl) was allowed to occur. There were three hypoglycemic groups: one in which hepatic autoregulation against hypoglycemia occurred in the absence of sympathetic nervous system input ( group 2 ), one in which autoregulation occurred in the presence of norepinephrine (NE) signaling to fat and muscle ( group 3 ), and one in which autoregulation occurred in the presence of NE signaling to fat, muscle, and liver ( group 4 ). Average net hepatic glucose balance (NHGB) during the last hour for groups 1-4 was -0.7 ± 0.1, 0.3 ± 0.1 ( P gluconeogenesis. Lowering glucose per se decreased nonhepatic glucose uptake by 8.9 mg·kg -1 ·min -1 , and the addition of increased neural efferent signaling to muscle and fat blocked glucose uptake further by 3.2 mg·kg -1 ·min -1 The addition of increased neural efferent input to liver did not affect NHGB or nonhepatic glucose uptake significantly. In conclusion, even in the absence of increases in counterregulatory hormones, the body can defend itself against hypoglycemia using glucose autoregulation and increased neural efferent signaling, both of which stimulate hepatic glucose production and limit glucose utilization. Copyright © 2017 the American Physiological Society.

  16. Severe Hypoglycemia Accompanied with Thyroid Crisis

    Directory of Open Access Journals (Sweden)

    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.

  17. Cross-cultural variation in symptom perception of hypoglycemia

    Directory of Open Access Journals (Sweden)

    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.

  18. Baroreflex Sensitivity Impairment During Hypoglycemia: Implications for Cardiovascular Control

    OpenAIRE

    Rao, Ajay D.; Bonyhay, Istvan; Dankwa, Joel; Baimas-George, Maria; Kneen, Lindsay; Ballatori, Sarah; Freeman, Roy; Adler, Gail K.

    2015-01-01

    Studies have shown associations between exposure to hypoglycemia and increased mortality, raising the possibility that hypoglycemia has adverse cardiovascular effects. In this study, we determined the acute effects of hypoglycemia on cardiovascular autonomic control. Seventeen healthy volunteers were exposed to experimental hypoglycemia (2.8 mmol/L) for 120 min. Cardiac vagal baroreflex function was assessed using the modified Oxford method before the initiation of the hypoglycemic-hyperinsul...

  19. Development of a New Fear of Hypoglycemia Scale: FH-15

    Science.gov (United States)

    Anarte Ortiz, Maria Teresa; Caballero, Francisco Felix; Ruiz de Adana, Maria Soledad; Rondan, Rosa Maria; Carreira, Monica; Dominguez-Lopez, Marta; Machado, Alberto; Gonzalo-Marin, Montserrat; Tapia, Maria Jose; Valdes, Sergio; Gonzalez-Romero, Stella; Soriguer, Federico C.

    2011-01-01

    Hypoglycemia is the most common adverse event associated with insulin treatment in diabetes. The consequences of hypoglycemia can be quite aversive and potentially life threatening. The physical sequelae provide ample reason for patients to fear hypoglycemia and avoid episodes. For these reasons, our purpose in this study was to develop a new…

  20. The economic impact of insulin-related hypoglycemia in Denmark

    DEFF Research Database (Denmark)

    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 u...

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

    Directory of Open Access Journals (Sweden)

    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

  2. Hypoglycemia-occipital syndrome: a specific neurologic syndrome following neonatal hypoglycemia?

    Science.gov (United States)

    Karimzadeh, Parvaneh; Tabarestani, Sepideh; Ghofrani, Mohammad

    2011-02-01

    This study attempted to elaborate the existence of a specific neurologic pattern observed in children who experienced neonatal hypoglycemia. Twenty-seven patients with seizure and history of neonatal hypoglycemia were compared with 28 children suffering from idiopathic occipital epilepsy. In both groups the most common type of seizure activities included eye movements and impaired consciousness responding well to treatment; however, ictal vomiting was more common in controls. Subjects were in epileptic and nonepileptic groups. Ninety percent of cases showed abnormal signal of the posterior head region on magnetic resonance imaging (MRI). A large number showed posterior abnormalities on electroencephalography (EEG). Visual loss with abnormal visual evoked potential was the most frequent visual finding. Fifty-five percent showed mild psychomotor retardation. This study demonstrates that neonatal hypoglycemia can induce a syndrome with a specific clinical spectrum consisting of epilepsy, visual disturbances, and psychomotor retardation. Hypoglycemia-occipital syndrome is an entity without statistically significant semiologic differences from the idiopathic type.

  3. Individual and societal consequences of hypoglycemia

    DEFF Research Database (Denmark)

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

    2015-01-01

    -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...

  4. Metabolic responses to hypoglycemia in juvenile diabetics

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Krarup, T

    1980-01-01

    /or orthostatic hypotension) and in seven control patients of similar age and duration of diabetes with out neuropathy. Before the hypoglycaemic episode, normoglycemia had been maintained for at least 10 hours. Following hypoglycemia, a slight but significant and similar increase in plasma glucagon was found...

  5. Rituximab induced hypoglycemia in non-Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    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.

  6. Toxicological Effects during and following Persistent Insulin-Induced Hypoglycaemia in Healthy Euglycaemic Rats

    DEFF Research Database (Denmark)

    Jensen, Vivi F. H.; Molck, Anne-Marie; Berthelsen, Line O.

    2017-01-01

    New insulin analogues with a longer duration of action and a ‘peakless’ pharmacokinetic profile have been developed to improve efficacy, safety and convenience for patients with diabetes. During non-clinical development, according to regulatory guidelines, these analogues are tested in healthy...... euglycaemic rats rendering them persistently hypoglycaemic. Little is known about the effect of persistent (24 hr/day) insulin-induced hypoglycaemia (IIH) in rats, complicating interpretation of results in pre-clinical studies with new longer-acting insulin analogues. In this study, we investigated...

  7. [Hypoglycemia as a cause of traffic accidents].

    Science.gov (United States)

    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.

  8. Insulin induces an EMT-like process in mammary epithelial cells MCF10A.

    Science.gov (United States)

    Rodriguez-Monterrosas, Cecilia; Díaz-Aragon, Ricardo; Leal-Orta, Elizabeth; Cortes-Reynosa, Pedro; Perez Salazar, Eduardo

    2017-12-13

    Diabetes mellitus has been related with an increased risk of breast cancer, whereas it has been suggested that links between diabetes mellitus and cancer are hyperinsulinemia, insulin resistance, hyperglycemia, and chronic inflammation induced by adipose tissue. Contribution of hyperinsulinemia to carcinogenesis is mediated through resistance to endogenous insulin and by exogenous insulin used in treatment. Epithelial to mesenchymal transition (EMT) is a process by which epithelial cells are transdifferentiated to a mesenchymal state that has been implicated in cancer progression. However, the role of insulin in EMT process has not been studied in detail. In the present study, we demonstrate that insulin induces downregulation of E-cadherin expression, accompanied with an increase of N-cadherin and vimentin expression, and an increase of MMP-2 and -9 secretions. Insulin also induces FAK activation, an increase of NFκB DNA binding activity, migration, and invasion of mammary non-tumorigenic epithelial cells MCF10A. In addition, migration requires the activity of insulin receptors and insulin-like growth factor receptor 1 (IGF1R). In summary, our results demonstrate that insulin induces an EMT-like process in MCF10A cells. © 2017 Wiley Periodicals, Inc.

  9. Insulin-induced enhancement of MCF-7 breast cancer cell response to 5-fluorouracil and cyclophosphamide.

    Science.gov (United States)

    Agrawal, Siddarth; Łuc, Mateusz; Ziółkowski, Piotr; Agrawal, Anil Kumar; Pielka, Ewa; Walaszek, Kinga; Zduniak, Krzysztof; Woźniak, Marta

    2017-06-01

    The study was designed to evaluate the potential use of insulin for cancer-specific treatment. Insulin-induced sensitivity of MCF-7 breast cancer cells to chemotherapeutic agents 5-fluorouracil and cyclophosphamide was evaluated. To investigate and establish the possible mechanisms of this phenomenon, we assessed cell proliferation, induction of apoptosis, activation of apoptotic and autophagic pathways, expression of glucose transporters 1 and 3, formation of reactive oxygen species, and wound-healing assay. Additionally, we reviewed the literature regarding theuse of insulin in cancer-specific treatment. We found that insulin increases the cytotoxic effect of 5-fluorouracil and cyclophosphamide in vitro up to two-fold. The effect was linked to enhancement of apoptosis, activation of apoptotic and autophagic pathways, and overexpression of glucose transporters 1 and 3 as well as inhibition of cell proliferation and motility. We propose a model for insulin-induced sensitization process. Insulin acts as a sensitizer of cancer cells to cytotoxic therapy through various mechanisms opening a possibility for metronomic insulin-based treatments.

  10. Insulin Induces Phosphorylation of Serine Residues of Translationally Controlled Tumor Protein in 293T Cells

    Directory of Open Access Journals (Sweden)

    Jeehye Maeng

    2015-04-01

    Full Text Available Insulin induces the activation of Na,K-ATPase while translationally controlled tumor protein (TCTP inhibits this enzyme and the associated pump activity. Because binding of insulin with its membrane receptor is known to mediate the phosphorylation of multiple intracellular proteins, phosphorylation of TCTP by insulin might be related to the sodium pump regulation. We therefore examined whether insulin induces TCTP phosphorylation in embryonic kidney 293T cells. Using immunoprecipitation and Western blotting, we found that insulin phosphorylates serine (Ser residues of TCTP. Following fractionation of the insulin-treated cells into cytosol and membrane fractions, phosphorylated TCTP at its Ser residue (p-Ser-TCTP was detected exclusively in the cytosolic part and not in the membrane fraction. Phosphorylation of TCTP reached maximum in about 10 min after insulin treatment in 293T cells. In studies of cell-type specificity of insulin-mediated phosphorylation of TCTP, insulin did not phosphorylate TCTP in HeLa cells. Computational prediction and immunoprecipitation using several constructs having Ser to Ala mutation at potential p-Ser sites of TCTP revealed that insulin phosphorylated the serine-9 and -15 residues of TCTP. Elucidations of how insulin-mediated TCTP phosphorylation promotes Na,K-ATPase activation, may offer potential therapeutic approaches to diseases associated with vascular activity and sodium pump dysregulation.

  11. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    International Nuclear Information System (INIS)

    Liu, Gang; Hitomi, Hirofumi; Hosomi, Naohisa; Lei, Bai; Nakano, Daisuke; Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu; Ma, Hong; Griendling, Kathy K.; Nishiyama, Akira

    2011-01-01

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: → Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. → Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. → Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. → Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  12. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Gang [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Hosomi, Naohisa [Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa (Japan); Lei, Bai; Nakano, Daisuke [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu [Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Ma, Hong [Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Griendling, Kathy K. [Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (United States); Nishiyama, Akira [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan)

    2011-10-15

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  13. Insulin-induced translocation of IR to the nucleus in insulin responsive cells requires a nuclear translocation sequence.

    Science.gov (United States)

    Kesten, Dov; Horovitz-Fried, Miriam; Brutman-Barazani, Tamar; Sampson, Sanford R

    2018-04-01

    Insulin binding to its cell surface receptor (IR) activates a cascade of events leading to its biological effects. The Insulin-IR complex is rapidly internalized and then is either recycled back to the plasma membrane or sent to lysosomes for degradation. Although most of the receptor is recycled or degraded, a small amount may escape this pathway and migrate to the nucleus of the cell where it might be important in promulgation of receptor signals. In this study we explored the mechanism by which insulin induces IR translocation to the cell nucleus. Experiments were performed cultured L6 myoblasts, AML liver cells and 3T3-L1 adipocytes. Insulin treatment induced a rapid increase in nuclear IR protein levels within 2 to 5 min. Treatment with WGA, an inhibitor of nuclear import, reduced insulin-induced increases nuclear IR protein; IR was, however, translocated to a perinuclear location. Bioinformatics tools predicted a potential nuclear localization sequence (NLS) on IR. Immunofluorescence staining showed that a point mutation on the predicted NLS blocked insulin-induced IR nuclear translocation. In addition, blockade of nuclear IR activation in isolated nuclei by an IR blocking antibody abrogated insulin-induced increases in IR tyrosine phosphorylation and nuclear PKCδ levels. Furthermore, over expression of mutated IR reduced insulin-induced glucose uptake and PKB phosphorylation. When added to isolated nuclei, insulin induced IR phosphorylation but had no effect on nuclear IR protein levels. These results raise questions regarding the possible role of nuclear IR in IR signaling and insulin resistance. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Detection of hypoglycemia associated EEG changes during sleep in type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Snogdal, Lena Sønder; Folkestad, Lars; Elsborg, Rasmus

    2012-01-01

    Nocturnal hypoglycemia is a feared complication to insulin treated diabetes. Impaired awareness of hypoglycemia (IAH) increases the risk of severe hypoglycemia. EEG changes are demonstrated during daytime hypoglycemia. In this explorative study, we test the hypothesis that specific hypoglycemia......-associated EEG-changes occur during sleep and are detectable in time for the patient to take action....

  15. 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...

  16. Enigma interacts with adaptor protein with PH and SH2 domains to control insulin-induced actin cytoskeleton remodeling and glucose transporter 4 translocation

    DEFF Research Database (Denmark)

    Barres, Romain; Grémeaux, Thierry; Gual, Philippe

    2006-01-01

    a critical role in actin cytoskeleton organization in fibroblastic cells. Because actin rearrangement is important for insulin-induced glucose transporter 4 (Glut 4) translocation, we studied the potential involvement of Enigma in insulin-induced glucose transport in 3T3-L1 adipocytes. Enigma m...

  17. 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

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

    Science.gov (United States)

    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.

  19. Hydrothermally modified slow release corn starch: a potential new therapeutic option for treating hypoglycemia in autoimmune hypoglycemia (Hirata's disease).

    Science.gov (United States)

    Lechner, K; Aulinger, B; Brand, S; Waldmann, E; Parhofer, K G

    2015-12-01

    We report the successful treatment of autoimmune hypoglycemia in an 82-year-old non-diabetic Caucasian male with hydrothermally modified slow release corn starch, a product which is used in other conditions associated with hypoglycemia, most typically glycogen storage disease type I. An 82-year-old-Caucasian male presented with recurrent spontaneous hypoglycemia as low as 30 mg/dl following in-patient treatment for community acquired pneumonia. During a fasting-test, symptomatic hypoglycemia occurred. Plasma concentrations of c-peptide and insulin were considerably elevated. Autoimmune hypoglycemia was confirmed by the presence of insulin autoantibodies. While dietary restriction alone did not result in sufficient glucose control in this patient with autoimmune hypoglycemia, treatment with hydrothermally modified slow release corn starch led to stable euglycemia. This easy, well tolerated and non-invasive treatment may constitute a new therapeutic option for hypoglycemia in patients with autoimmune hypoglycemia who do not achieve sufficient control of hypoglycemia by dietary restriction alone.

  20. Insulin induces long-term depression of VTA dopamine neurons via an endocannabinoid-mediated mechanism

    Science.gov (United States)

    Labouèbe, Gwenaël; Liu, Shuai; Dias, Carine; Zou, Haiyan; Wong, Jovi C.Y.; Karunakaran, Subashini; Clee, Susanne M.; Phillips, Anthony; Boutrel, Benjamin; Borgland, Stephanie L.

    2014-01-01

    The prevalence of obesity has drastically increased over the last few decades. Exploration into how hunger and satiety signals influence the reward system can help us to understand non-homeostatic mechanisms of feeding. Evidence suggests that insulin may act in the ventral tegmental area (VTA), a critical site for reward-seeking behavior, to suppress feeding. However, the neural mechanisms underlying insulin effects in the VTA remain unknown. We demonstrate that insulin, a circulating catabolic peptide that inhibits feeding, can induce a long-term depression (LTD) of excitatory synapses onto VTA dopamine neurons. This effect requires endocannabinoid-mediated presynaptic inhibition of glutamate release. Furthermore, after a sweetened high fat meal, which elevates endogenous insulin levels, insulin-induced LTD is occluded. Finally, insulin in the VTA reduces food anticipatory behavior and conditioned place preference for food. Taken together, these results suggest that insulin in the VTA suppresses excitatory synaptic transmission and reduces salience of food-related cues. PMID:23354329

  1. Effect of insulin-induced hypoglycaemia on the peripheral nervous system

    DEFF Research Database (Denmark)

    Jensen, Vivi Flou Hjorth; Mølck, A.-M.; Bøgh, I. B.

    2014-01-01

    Insulin-induced hypoglycaemia (IIH) is a common acute side effect in type 1 and type 2 diabetic patients, especially during intensive insulin therapy. The peripheral nervous system (PNS) depends on glucose as its primary energy source during normoglycaemia and, consequently, it may be particularly...... state exceeds a certain level of severity and duration, resulting in a sensory-motor neuropathy with associated skeletal muscle atrophy. Large myelinated motor fibres appear to be particularly vulnerable. Thus, although the PNS is not an obligate glucose consumer, as is the brain, it appears to be more...... prone to IIH than the central nervous system when hypoglycaemia is not severe (blood glucose level ≤ 2 mm), possibly reflecting a preferential protection of the brain during periods of inadequate glucose availability. With a primary focus on evidence from experimental animal studies investigating...

  2. Effect of insulin-induced hypoglycaemia on the central nervous system

    DEFF Research Database (Denmark)

    Jensen, Vivi Flou Hjorth; Bøgh, I. B.; Lykkesfeldt, Jens

    2014-01-01

    normoglycaemia. Brain glucose concentrations, being approximately 15-20% of the blood glucose concentration in humans, are rigorously maintained during hypoglycaemia through adaptions such as increased cerebral glucose transport, decreased cerebral glucose utilisation and, possibly, by using central nervous......Insulin-induced hypoglycaemia (IIH) is a major acute complication in type 1 as well as in type 2 diabetes, particularly during intensive insulin therapy. The brain plays a central role in the counter-regulatory response by eliciting parasympathetic and sympathetic hormone responses to restore...... system glycogen as a glucose reserve. However, during sustained hypoglycaemia, the brain cannot maintain a sufficient glucose influx and, as the cerebral hypoglycaemia becomes severe, electroencephalogram changes, oxidative stress and regional neuronal death ensues. With particular focus on evidence from...

  3. The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity.

    Science.gov (United States)

    de Laat, M A; Kyaw-Tanner, M T; Nourian, A R; McGowan, C M; Sillence, M N; Pollitt, C C

    2011-04-15

    Metalloproteinases have been implicated in the pathogenesis of equine laminitis and other inflammatory conditions, through their role in the degradation and remodelling of the extracellular matrix environment. Matrix metalloproteinases (MMPs) and their inhibitors are present in normal equine lamellae, with increased secretion and activation of some metalloproteinases reported in horses with laminitis associated with systemic inflammation. It is unknown whether these enzymes are involved in insulin-induced laminitis, which occurs without overt systemic inflammation. In this study, gene expression of MMP-2, MMP-9, MT1-MMP, ADAMTS-4 and TIMP-3 was determined in the lamellar tissue of normal control horses (n=4) and horses that developed laminitis after 48 h of induced hyperinsulinaemia (n=4), using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Protein concentrations of MMP-2 and MMP-9 were also examined using gelatin zymography in horses subject to prolonged hyperinsulinaemia for 6h (n=4), 12h (n=4), 24h (n=4) and 48 h (n=4), and in normal control horses (n=4). The only change in gene expression observed was an upregulation of MMP-9 (plaminitis (48 h). Zymographical analysis showed an increase (plaminitis (48 h), whereas pro MMP-2 was present in similar concentration in the tissue of all horses. Thus, MMP-2, MT1-MMP, TIMP-3 and ADAMTS-4 do not appear to play a significant role in the pathogenesis of insulin-induced laminitis. The increased expression of MMP-9 may be associated with the infiltration of inflammatory leukocytes, or may be a direct result of hyperinsulinaemia. The exact role of MMP-9 in basement membrane degradation in laminitis is uncertain as it appears to be present largely in the inactive form. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Hypoglycemia in Type 1 Diabetic Pregnancy

    Science.gov (United States)

    Heller, Simon; Damm, Peter; Mersebach, Henriette; Skjøth, Trine Vang; Kaaja, Risto; Hod, Moshe; Durán-García, Santiago; McCance, David; Mathiesen, Elisabeth R.

    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 (IAsp versus human insulin were 0.9 versus 2.4, 0.9 versus 2.4, 0.3 versus 1.2, and 0.2 versus 2.2 episodes per patient per year, respectively (NS). CONCLUSIONS These data suggest that initiation of insulin analog treatment preconception rather than during early pregnancy may result in a lower risk of severe hypoglycemia in women with type 1 diabetes. PMID:20007944

  5. 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 redun...

  6. Hypoglycemia is associated with intensive care unit mortality

    NARCIS (Netherlands)

    Hermanides, J.; Bosman, R.J.; Vriesendorp, T.M.; Dotsch, R.; Rosendaal, F.R.; Zandstra, D.F.; Hoekstra, J.B.L.; DeVries, J.H.

    2010-01-01

    Objective: The implementation of intensive insulin therapy in the intensive care unit is accompanied by an increase in hypoglycemia. We studied the relation between hypoglycemia on intensive care unit mortality, because the evidence on this subject is conflicting. Design: Retrospective database

  7. Hypoglycemia is associated with intensive care unit mortality

    NARCIS (Netherlands)

    Hermanides, Jeroen; Bosman, Robert J.; Vriesendorp, Titia M.; Dotsch, Ron; Rosendaal, Frits R.; Zandstra, Durk F.; Hoekstra, Joost B. L.; DeVries, J. Hans

    2010-01-01

    OBJECTIVE: The implementation of intensive insulin therapy in the intensive care unit is accompanied by an increase in hypoglycemia. We studied the relation between hypoglycemia on intensive care unit mortality, because the evidence on this subject is conflicting. DESIGN: Retrospective database

  8. 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...

  9. Profound postanesthetic hypoglycemia attributable to glucocorticoid deficiency in 2 dogs.

    OpenAIRE

    Lane, I F; Matwichuk, C L; Carpenter, L G; Behrend, E N

    1999-01-01

    Glucocorticoid deficiency was diagnosed as the cause of severe postanesthetic hypoglycemia in 2 dogs. Prior signs of systemic illness were not described in either dog; however, preoperative hematologic findings were consistent with glucocorticoid deficiency. Fasting hypoglycemia is a possible complication of chronic adrenal insufficiency primarily because of impaired gluconeogenesis.

  10. 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

  11. Recurrent Hypoglycemia in a Hemodialysis Patient Related to Propoxyphene Treatment

    Directory of Open Access Journals (Sweden)

    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.

  12. QT measurement and heart rate correction during hypoglycemia

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...... 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...... a significant impact on the prolongation of QT during hypoglycemia. Heart rate correction may also influence the QT during hypoglycemia while the type of insulin is insignificant. Prolongation of QTc in this study did not reach pathologic values suggesting that QTc prolongation cannot fully explain the dead...

  13. 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....

  14. 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

    of relatives. RESEARCH DESIGN AND METHODS: A cross-sectional paired questionnaire survey on hypoglycemia and the state of awareness was used in our study comprising 284 unselected adult patients with type 1 diabetes and their closest cohabitant. The cohabitant questionnaires also addressed involvement...... and concern. RESULTS: The agreement between assessments of rates of severe hypoglycemia and state of awareness made by patients and cohabitants was weak (kappa 0.404 and 0.442, respectively; P Cohabitants recalled more episodes of severe hypoglycemia than patients (2.7 vs. 1.6 episodes.......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....

  15. [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.

  16. Baroreflex Sensitivity Impairment During Hypoglycemia: Implications for Cardiovascular Control

    Science.gov (United States)

    Rao, Ajay D.; Bonyhay, Istvan; Dankwa, Joel; Baimas-George, Maria; Kneen, Lindsay; Ballatori, Sarah; Adler, Gail K.

    2016-01-01

    Studies have shown associations between exposure to hypoglycemia and increased mortality, raising the possibility that hypoglycemia has adverse cardiovascular effects. In this study, we determined the acute effects of hypoglycemia on cardiovascular autonomic control. Seventeen healthy volunteers were exposed to experimental hypoglycemia (2.8 mmol/L) for 120 min. Cardiac vagal baroreflex function was assessed using the modified Oxford method before the initiation of the hypoglycemic-hyperinsulinemic clamp protocol and during the last 30 min of hypoglycemia. During hypoglycemia, compared with baseline euglycemic conditions, 1) baroreflex sensitivity decreases significantly (19.2 ± 7.5 vs. 32.9 ± 16.6 ms/mmHg, P baroreflex activation increases significantly (the baroreflex function shifts to the right; 120 ± 14 vs. 112 ± 12 mmHg, P < 0.005), and 3) the maximum R-R interval response (1,088 ± 132 vs. 1,496 ± 194 ms, P < 0.001) and maximal range of the R-R interval response (414 ± 128 vs. 817 ± 183 ms, P < 0.001) decrease significantly. These findings indicate reduced vagal control and impaired cardiovascular homeostasis during hypoglycemia. PMID:26438610

  17. Spontaneous Hypoglycemia After Islet Autotransplantation for Chronic Pancreatitis.

    Science.gov (United States)

    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.

  18. Cotrimoxazole-Induced Hypoglycemia in an HIV-Infected Patient

    Directory of Open Access Journals (Sweden)

    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.

  19. Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes.

    Science.gov (United States)

    Manowsky, Julia; Camargo, Rodolfo Gonzalez; Kipp, Anna P; Henkel, Janin; Püschel, Gerhard P

    2016-06-01

    Overweight and obesity are associated with hyperinsulinemia, insulin resistance, and a low-grade inflammation. Although hyperinsulinemia is generally thought to result from an attempt of the β-cell to compensate for insulin resistance, there is evidence that hyperinsulinaemia itself may contribute to the development of insulin resistance and possibly the low-grade inflammation. To test this hypothesis, U937 macrophages were exposed to insulin. In these cells, insulin induced expression of the proinflammatory cytokines IL-1β, IL-8, CCL2, and OSM. The insulin-elicited induction of IL-1β was independent of the presence of endotoxin and most likely mediated by an insulin-dependent activation of NF-κB. Supernatants of the insulin-treated U937 macrophages rendered primary cultures of rat hepatocytes insulin resistant; they attenuated the insulin-dependent induction of glucokinase by 50%. The cytokines contained in the supernatants of insulin-treated U937 macrophages activated ERK1/2 and IKKβ, resulting in an inhibitory serine phosphorylation of the insulin receptor substrate. In addition, STAT3 was activated and SOCS3 induced, further contributing to the interruption of the insulin receptor signal chain in hepatocytes. These results indicate that hyperinsulinemia per se might contribute to the low-grade inflammation prevailing in overweight and obese patients and thereby promote the development of insulin resistance particularly in the liver, because the insulin concentration in the portal circulation is much higher than in all other tissues. Copyright © 2016 the American Physiological Society.

  20. Analysis of regulatory mechanisms of an insulin-inducible SHARP-2 gene by (S)-Equol.

    Science.gov (United States)

    Haneishi, Ayumi; Takagi, Katsuhiro; Asano, Kosuke; Yamamoto, Taichi; Tanaka, Takashi; Nakamura, Soichiro; Noguchi, Tamio; Yamada, Kazuya

    2012-09-01

    Small compounds that activate the insulin-dependent signaling pathway have potential therapeutic applications in controlling type 2 diabetes mellitus. The rat enhancer of split- and hairy-related protein-2 (SHARP-2) is an insulin-inducible transcription factor that decreases expression of the phosphoenolpyruvate carboxykinase gene, a gluconeogenic enzyme gene. In this study, we screened for soybean isoflavones that can induce the rat SHARP-2 gene expression and analyzed their mechanism(s). Genistein and (S)-Equol, a metabolite of daidzein, induced rat SHARP-2 gene expression in H4IIE rat hepatoma cells. The (S)-Equol induction was mediated by both the phosphoinositide 3-kinase- and protein kinase C (PKC)-pathways. When a dominant negative form of atypical PKC lambda (aPKCλ) was expressed, the induction of SHARP-2 mRNA level by (S)-Equol was inhibited. In addition, Western blot analyses showed that (S)-Equol rapidly activated both aPKCλ and classical PKC alpha. Furthermore, the (S)-Equol induction was inhibited by treatment with a RNA polymerase inhibitor or a protein synthesis inhibitor. Finally, a reporter gene assay revealed that the transcriptional stimulation by (S)-Equol was mediated by nucleotide sequences located between -4687 and -4133 of the rat SHARP-2 gene. Thus, we conclude that (S)-Equol is an useful dietary supplement to control type 2 diabetes mellitus. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice

    DEFF Research Database (Denmark)

    Meijer, Rick I; Bakker, Wineke; Alta, Caro-Lynn A F

    2013-01-01

    (-/-) were studied. In AMPKa2(-/-) resistance arteries, insulin caused vasoconstriction in the presence of PVAT, and AMPKa2(+/+) resistance arteries showed a neutral response. On the other hand, inhibition of the inflammatory kinase Jun NH(2)-terminal kinase (JNK) in db/db PVAT restored insulin...... in muscle, the underlying mechanisms, and how obesity disturbs this vasodilation. Insulin-induced vasoreactivity of resistance arteries was studied with PVAT from C57BL/6 or db/db mice. PVAT weight in muscle was higher in db/db mice compared with C57BL/6 mice. PVAT from C57BL/6 mice uncovered insulin......-induced vasodilation; this vasodilation was abrogated with PVAT from db/db mice. Blocking adiponectin abolished the vasodilator effect of insulin in the presence of C57BL/6 PVAT, and adiponectin secretion was lower in db/db PVAT. To investigate this interaction further, resistance arteries of AMPKa2(+/+) and AMPKa2...

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

    Science.gov (United States)

    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.

  3. Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells.

    Science.gov (United States)

    Carranza, Andrea; Musolino, Patricia L; Villar, Marcelo; Nowicki, Susana

    2008-12-01

    The inward l-dihydroxyphenylalanine (L-dopa) transport supplies renal proximal tubule cells (PTCs) with the precursor for dopamine synthesis. We have previously described insulin-induced stimulation of L-dopa uptake into PTCs. In the present paper we examined insulin-related signaling pathways involved in the increase of l-dopa transport into isolated rat PTCs. Insulin (50-500 microU/ml) increased L-dopa uptake by PTCs, reaching the maximal increment (60% over the control) at 200 microU/ml. At this concentration, insulin also increased insulin receptor tyrosine phosphorylation. Both effects were abrogated by the tyrosine kinase inhibitor genistein (5 microM). In line, inhibition of the protein tyrosine phosphatase by pervanadate (0.2-100 microM) caused a concentration-dependent increase in both the uptake of L-dopa (up to 400%) and protein tyrosine phosphorylation. A synergistic effect between pervanadate and insulin on L-dopa uptake was observed only when threshold (0.2 microM), but not maximal (5 microM), concentrations of pervanadate were assayed. Insulin-induced stimulation of L-dopa uptake was also abolished by inhibition of phosphatidylinositol 3-kinase (PI3K; 100 nM wortmannin, and 25 microM LY-294002) and protein kinase C (PKC; 1 microM RO-318220). Insulin-induced activation of PKC-zeta was confirmed in vitro by its translocation from the cytosol to the membrane fraction, and in vivo by immunohistochemistry studies. Insulin caused a wortmannin-sensitive increase in Akt/protein kinase B (Akt/PKB) phosphorylation and a dose-dependent translocation of Akt/PKB to the membrane fraction. Our findings suggest that insulin activates PKC-zeta, and Akt/PKB downstream of PI3K, and that these pathways contribute to the insulin-induced increase of L-dopa uptake into PTCs.

  4. 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)

  5. Overestimation of hypoglycemia in infants with a high hematocrit

    NARCIS (Netherlands)

    Kemperman, Hans; van Solinge, Wouter W; de Vooght, Karen MK

    Background: In neonates, hypoglycemia is an emergency condition requiring urgent treatment. Therefore, rapid and reliable blood glucose measurements are necessary. However, this step has been proven difficult because of both analytical and preanalytical variables. In our children's hospital, we

  6. Refractory hypoglycemia in a patient with functional adrenal cortical carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  7. Fasting time duration modulates the onset of insulin-induced hypoglycemic seizures in mice.

    Science.gov (United States)

    Pitchaimani, Vigneshwaran; Arumugam, Somasundaram; Thandavarayan, Rajarajan Amirthalingam; Karuppagounder, Vengadeshprabhu; Afrin, Mst Rejina; Sreedhar, Remya; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Nakamura, Takashi; Suzuki, Kenji; Nakamura, Masahiko; Ueno, Kazuyuki; Watanabe, Kenichi

    2016-09-01

    Fasting (48h) in mice causes resistance to insulin-induced hypoglycemic seizures (IIHS) but in rats fasting (14-16h) predisposes IIHS. So we suspect the duration of fasting may possibly affect the onset of seizures and in this study, we investigated the IIHS by administering 8 Units (U) insulin (INS)/k.g., intraperitoneally to 8 weeks old male C57BL6/J mice. The mice were divided into group 1 (non-fasted), group 2 (6h fasted) and group 3 (24h fasted) and we administered the 8U INS. The first behavioral hypoglycemic seizure symptoms such as jump, clonus or barrel rotations considered as seizure onset and we analyzed the blood glucose level (BGL) and serum beta-hydroxybutyrate (BHB) level. The time of first seizure onset in group 1 was 109.7±4.3min, group 2 was 46.50±3.9min and group 3 was 165.4±13.26min. The seizure onset time in group 2 was significantly decreased compared to group 1. The seizure onset time in group 3 was significantly increased compared to group 1 and group 2. The decreased BGL after INS administration was correlated with the seizure onset time in group 1 and group 2 but not in group 3. The BHB level in group 3 was significantly higher compared to group 1 and 2. Our data show that the fasting time duration significantly modulates the onset of hypoglycemic seizures. The opposite effect of 6h or 24h fasting time duration is likely caused by different BHB levels. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Sleep-related hypoglycemia-associated autonomic failure in type 1 diabetes: reduced awakening from sleep during hypoglycemia.

    Science.gov (United States)

    Banarer, Salomon; Cryer, Philip E

    2003-05-01

    Given that iatrogenic hypoglycemia often occurs during the night in people with type 1 diabetes, we tested the hypothesis that physiological, and the resulting behavioral, defenses against developing hypoglycemia-already compromised by absent glucagon and attenuated epinephrine and neurogenic symptom responses-are further compromised during sleep in type 1 diabetes. To do so, we studied eight adult patients with uncomplicated type 1 diabetes and eight matched nondiabetic control subjects with hyperinsulinemic stepped hypoglycemic clamps (glucose steps of approximately 85, 75, 65, 55, and 45 mg/dl) in the morning (0730-1230) while awake and at night (2100-0200) while awake throughout and while asleep from 0000 to 0200 in random sequence. Plasma epinephrine (P = 0.0010), perhaps norepinephrine (P = 0.0838), and pancreatic polypeptide (P = 0.0034) responses to hypoglycemia were reduced during sleep in diabetic subjects (the final awake versus asleep values were 240 +/- 86 and 85 +/- 47, 205 +/- 24 and 148 +/- 17, and 197 +/- 45 and 118 +/- 31 pg/ml, respectively), but not in the control subjects. The diabetic subjects exhibited markedly reduced awakening from sleep during hypoglycemia. Sleep efficiency (percent time asleep) was 77 +/- 18% in the diabetic subjects, but only 26 +/- 8% (P = 0.0109) in the control subjects late in the 45-mg/dl hypoglycemic steps. We conclude that autonomic responses to hypoglycemia are reduced during sleep in type 1 diabetes, and that, probably because of their reduced sympathoadrenal responses, patients with type 1 diabetes are substantially less likely to be awakened by hypoglycemia. Thus both physiological and behavioral defenses are further compromised during sleep. This sleep-related hypoglycemia-associated autonomic failure, in the context of imperfect insulin replacement, likely explains the high frequency of nocturnal hypoglycemia in type 1 diabetes.

  9. Recurrent hypoglycemia increases anxiety and amygdala norepinephrine release during subsequent hypoglycemia

    Directory of Open Access Journals (Sweden)

    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.

  10. An uncommon cause of hypoglycemia: insulin autoimmune syndrome.

    Science.gov (United States)

    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.

  11. Hypoglycemia associated with refeeding syndrome in a cat.

    Science.gov (United States)

    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.

  12. 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

  13. Hypoglycemia-Related Electroencephalogram Changes Assessed by Multiscale Entropy

    DEFF Research Database (Denmark)

    Fabris, C.; Sparacino, G.; Sejling, A. S.

    2014-01-01

    physiopathological conditions have never been assessed in hypoglycemia. The present study investigates if properties of the EEG signal measured by nonlinear entropy-based algorithms are altered in a significant manner when a state of hypoglycemia is entered. Subjects and Methods: EEG was acquired from 19 patients...... derivation in the two glycemic intervals was assessed using the multiscale entropy (MSE) approach, obtaining measures of sample entropy (SampEn) at various temporal scales. The comparison of how signal irregularity measured by SampEn varies as the temporal scale increases in the two glycemic states provides...

  14. Risk of Hospitalization for Hypoglycemia in Older Patients with Diabetes Using Antipsychotic Drugs

    NARCIS (Netherlands)

    van Keulen, Kris; van der Linden, Paul D; Souverein, Patrick C; Heerdink, Eibert R; Egberts, Toine; Knol, Wilma

    2015-01-01

    OBJECTIVE: Antipsychotics may disrupt metabolic regulation in patients with diabetes mellitus. The risk of hypoglycemia in older users of antipsychotics with diabetes is largely unknown. Therefore, we investigated the association between the use of antipsychotic drugs and hypoglycemia requiring

  15. Hypoglycemia in pregnant women with type 1 diabetes: predictors and role of metabolic control

    DEFF Research Database (Denmark)

    Nielsen, Lene Ringholm; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

    2008-01-01

    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....

  16. Insulin induces an increase in cytosolic glucose levels in 3T3-L1 cells with inhibited glycogen synthase activation.

    Science.gov (United States)

    Chowdhury, Helena H; Kreft, Marko; Jensen, Jørgen; Zorec, Robert

    2014-10-02

    Glucose is an important source of energy for mammalian cells and enters the cytosol via glucose transporters. It has been thought for a long time that glucose entering the cytosol is swiftly phosphorylated in most cell types; hence the levels of free glucose are very low, beyond the detection level. However, the introduction of new fluorescence resonance energy transfer-based glucose nanosensors has made it possible to measure intracellular glucose more accurately. Here, we used the fluorescent indicator protein (FLIPglu-600µ) to monitor cytosolic glucose dynamics in mouse 3T3-L1 cells in which glucose utilization for glycogen synthesis was inhibited. The results show that cells exhibit a low resting cytosolic glucose concentration. However, in cells with inhibited glycogen synthase activation, insulin induced a robust increase in cytosolic free glucose. The insulin-induced increase in cytosolic glucose in these cells is due to an imbalance between the glucose transported into the cytosol and the use of glucose in the cytosol. In untreated cells with sensitive glycogen synthase activation, insulin stimulation did not result in a change in the cytosolic glucose level. This is the first report of dynamic measurements of cytosolic glucose levels in cells devoid of the glycogen synthesis pathway.

  17. 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

    hypoglycemia. A1C, median SMPG, and fluctuations in SMPG decreased during pregnancy, with no differences between women with and without severe hypoglycemia. Logistic regression analysis identified history of severe hypoglycemia the year preceding pregnancy (odds ratio 3.3 [95% CI 1.2-9.2]) and impaired...

  18. Hypothalamic-Pituitary-Adrenal Axis Programming after Recurrent Hypoglycemia during Development

    Directory of Open Access Journals (Sweden)

    Raghavendra Rao

    2015-08-01

    Full Text Available Permanent brain injury is a complication of recurrent hypoglycemia during development. Recurrent hypoglycemia also has adverse consequences on the neuroendocrine system. Hypoglycemia-associated autonomic failure, characterized by ineffective glucose counterregulation during hypoglycemia, is well described in children and adults on insulin therapy for diabetes mellitus. Whether recurrent hypoglycemia also has a programming effect on the hypothalamus-pituitary-adrenal cortex (HPA axis has not been well studied. Hypoglycemia is a potent stress that leads to increased glucocorticoid secretion in all age groups, including the perinatal period. Other conditions associated with exposure to excess glucocorticoid in the perinatal period have a programming effect on the HPA axis activity. Limited animal data suggest the possibility of similar programming effect after recurrent hypoglycemia in the postnatal period. The age at exposure to hypoglycemia likely determines the HPA axis response in adulthood. Recurrent hypoglycemia in the early postnatal period likely leads to a hyperresponsive HPA axis, whereas recurrent hypoglycemia in the late postnatal period lead to a hyporesponsive HPA axis in adulthood. The age-specific programming effects may determine the neuroendocrine response during hypoglycemia and other stressful events in individuals with history of recurrent hypoglycemia during development.

  19. 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 ...

  20. Hypoglycemia-Induced Changes in the Electroencephalogram: An Overview

    DEFF Research Database (Denmark)

    Blaabjerg, Lykke; Juhl, Claus Bogh

    2016-01-01

    to the brain, where glucose is the primary metabolic fuel. The brain is one of the first organs to be affected by hypoglycemia. Shortage of glucose in the brain, or neuroglycopenia, results in a gradual loss of cognitive functions causing slower reaction time, blurred speech, loss of consciousness, seizures...

  1. A Rare Case of Noninsulinoma Pancreatogenous Hypoglycemia Syndrome

    Directory of Open Access Journals (Sweden)

    Jeffrey Nadelson

    2012-01-01

    Full Text Available As the obesity pandemic continues to worsen and medical interventions remain only moderately effective, bariatric surgery remains an important option for patients. In certain instances, patients who have undergone the procedure experience postprandial symptoms of neuroglycopenia caused by noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS. NIPHS is a recently described syndrome and is also very rare, and therapeutic approaches are still under debate. We report the case of a 51-year-old female who underwent Roux-en-Y gastric bypass and presented with episodic postprandial hypoglycemia 2 years after surgery. An insulinoma was absent from all abdominal imaging. Fasting C-peptide, insulin, and glucose were normal. Due to the possibility of NIPHS, clinical treatment was commenced with acarbose, leading to a significant reduction of hypoglycemic episodes. NIPHS occurs in approximately 0.5% to 7% of patients with hyperinsulinemic hypoglycemia. Sporadic hypoglycemia postgastric bypass is an important entity that should be understood by all surgeons and internists who are involved in postgastric bypass care.

  2. Postprandial hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    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...

  3. Persistent hyperinsulinemic hypoglycemia of infancy: long-term ...

    African Journals Online (AJOL)

    Aim The aim of this study was to investigate the long-term outcome of six children with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) after pancreatectomy who have been followed since 1990 at the Riyadh Military Hospital, Riyadh, Kingdom of Saudi Arabia. Patients and methods Data from six patients were ...

  4. [Diagnostic evaluation of persistent neonatal hypoglycemia using the fasting test: behavior of glucoregulatory hormones and intermediary metabolites (1)].

    Science.gov (United States)

    Lischka, A

    1987-01-01

    The effect of insulin induced hypoglycemia on glucoregulatory hormones and intermediary substrates was studied in four infants (three boys and one girl, ages 12-89 days) with persistent hyperinsulinism secondary to nesidioblastosis (two) or microadenoma of the pancreas (two). During the "fasting test" the following data expressed as mean basal plasma values +/- SEM vs. mean hypoglycemic values +/- SEM were obtained: insulin (57.3 +/- 17.9 vs. 27.5 +/- 10.6 microU/ml), C-peptide (4.9 +/- 1.1 vs. 3.5 +/- 0.9 ng/ml), free fatty acids (0.30 +/- 0.01 vs. 0.32 +/- 0.02 mmol/l), beta-hydroxybutyrate (less than 0.03 vs. 0.05 +/- 0.02 mmol/l), alanine (204.0 +/- 67.5 vs. 228.3 +/- 64.9 mumol/l), lactate (5.3 +/- 0.7 vs. 5.4 +/- 1.1 mg/dl), pyruvate (41.3 +/- 4.8 vs. 19.7 +/- 4.2 mg/dl). These data suggest "inappropriate" elevation of insulin and C-peptide levels, inhibition of lipolysis and lack of gluconeogenic substrates secondary to endogenous HI. An increase of cortisol (6.5 +/- 4.1 vs. 16.3 +/- 5.7 micrograms/dl), adrenaline (0.015 +/- 0.05 vs. 0.25 +/- 0.24 ng/ml) (3 out of 4) and noradrenaline (0.28 +/- 0.06 vs. 0.64 +/- 0.14 ng/ml) was noted, whereas only minute increase was found for glucagon (134.3 +/- 51.7 vs. 177.0 +/- 76.2 pg/ml) and HGH (5.7 +/- 1.1 vs. 7.1 +/- 1.1 ng/ml). Although some stimulation of neonatal glucoregulatory hormones was evident, this was not strong enough for counteracting endogenous HI.

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

    DEFF Research Database (Denmark)

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

    2018-01-01

    report results from the HypoAna trial comparing all-analog-insulin therapy (aspart/detemir) with all-human-insulin therapy (neutral protamine Hagedorn/regular) on non-severe hypoglycemia (symptomatic and asymptomatic hypoglycemia) as assessed by blinded CGM and compared with data obtained by self-monitoring......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...

  6. The Effects of Insulin-Induced Hypoglycaemia on Tyrosine Hydroxylase Phosphorylation in Rat Brain and Adrenal Gland.

    Science.gov (United States)

    Senthilkumaran, Manjula; Johnson, Michaela E; Bobrovskaya, Larisa

    2016-07-01

    In this study we investigated the effects of insulin-induced hypoglycaemia on tyrosine hydroxylase (TH) protein and TH phosphorylation in the adrenal gland, C1 cell group, locus coeruleus (LC) and midbrain dopaminergic cell groups that are thought to play a role in response to hypoglycaemia and compared the effects of different concentrations of insulin in rats. Insulin (1 and 10 U/kg) treatment caused similar reductions in blood glucose concentration (from 7.5-9 to 2-3 mmol/L); however, plasma adrenaline concentration was increased 20-30 fold in response to 10 U/kg insulin and only 14 fold following 1 U/kg. Time course studies (at 10 U/kg insulin) revealed that in the adrenal gland, Ser31 phosphorylation was increased between 30 and 90 min (4-5 fold), implying that TH was activated to increase catecholamine synthesis in adrenal medulla to replenish the stores. In the brain, Ser19 phosphorylation was limited to certain dopaminergic groups in the midbrain, while Ser31 phosphorylation was increased in most catecholaminergic regions at 60 min (1.3-2 fold), suggesting that Ser31 phosphorylation may be an important mechanism to maintain catecholamine synthesis in the brain. Comparing the effects of 1 and 10 U/kg insulin revealed that Ser31 phosphorylation was increased to similar extent in the adrenal gland and C1 cell group in response to both doses whereas Ser31 and Ser19 phosphorylation were only increased in response to 1 U/kg insulin in LC and in response to 10 U/kg insulin in most midbrain regions. Thus, the adrenal gland and some catecholaminergic brain regions become activated in response to insulin administration and brain catecholamines may be important for initiation of physiological defences against insulin-induced hypoglycaemia.

  7. Insulin-Induced Microvascular Recruitment in Skin and Muscle are Related and Both are Associated with Whole-Body Glucose Uptake

    NARCIS (Netherlands)

    Meijer, R.I.; de Boer, M.P.; Groen, M.R.; Eringa, E.C.; Rattigan, S.; Barrett, E.J.; Smulders, Y.M.; Serné, E.H.

    2012-01-01

    Objective: Insulin-induced capillary recruitment is considered a determinant of insulin-mediated glucose uptake. Insulin action on the microvasculature has been assessed in skin; however, there is concern as to whether the vascular responses observed in skin reflect those in the muscle. We

  8. A retrospective study on epidemiology of hypoglycemia in Emergency Department

    Directory of Open Access Journals (Sweden)

    Juvva Gowtham Kumar

    2017-01-01

    Full Text Available Background: Hypoglycemia is one among the leading causes for Emergency Department (ED visits and is the most common and easily preventable endocrine emergency. This study is aimed at assessing the incidence and elucidating the underlying causes of hypoglycemia. Materials and Methods: A retrospective, observational study which included patients registering in ED with a finger prick blood glucose ≤60 mg/dl at the time of arrival. All patients aged above 15 years with the above inclusion criteria during the period of August 2010 to July 2013 were selected. The study group was categorized based on diabetic status into diabetic and nondiabetic groups. Results: A total of 1196 hypoglycemic episodes encountered at the ED during the study period were included, and of which 772 with complete data were analyzed. Underlying causes for hypoglycemia in the diabetic group (535 mainly included medication related 320 (59.81%, infections 108 (20.19%, and chronic kidney disease 61 (11.40%. Common underlying causes of hypoglycemia in nondiabetic group (237, 30.69% included infections 107 (45.15%, acute/chronic liver disease 42 (17.72%, and malignancies 22 (9.28%. Among diabetic subjects on antidiabetic medications (n = 320, distribution over 24 h duration clearly reported two peaks at 8th and 21st h. The incidence of hypoglycemia and death per 1000 ED visits were 16.41 and 0.73 in 2011, 16.19 and 0.78 in 2012, 17.20 and 1.22 in 2013 with an average of 16.51 and 0.91, respectively. Conclusion: Bimodal distribution with peaks in incidences of hypoglycemic attacks at 8th and 21st h based on hourly distribution in a day can be correlated with the times just before next meal. None of the patients should leave ED without proper evaluation of the etiology of hypoglycemia and the problem should be addressed at each individual level. Increasing incidence of death over the years is alarming, and further studies are needed to conclude the root cause.

  9. Effect of the GLP-1 Receptor Agonist Lixisenatide on Counterregulatory Responses to Hypoglycemia in Subjects With Insulin-Treated Type 2 Diabetes.

    Science.gov (United States)

    Farngren, Johan; Persson, Margaretha; Ahrén, Bo

    2016-02-01

    Counterregulatory responses are critical to prevent hypoglycemia in subjects with type 2 diabetes. This is particularly important in insulin-treated patients. This study explored the effect of the glucagon-like peptide 1 receptor agonist lixisenatide on the hormonal counterregulatory responses to insulin-induced hypoglycemia when added to basal insulin therapy in subjects with type 2 diabetes. The study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 18 subjects with type 2 diabetes (11 males) with a mean age of 55 years, diabetes duration of 12 years, HbA1c level of 7.7%, fasting blood glucose (FBG) concentration of 9.7 mmol/L, and a BMI of 33 kg/m(2), who were treated with basal insulin (mean duration 7 years, daily dose 39 units/day) and metformin (mean daily dose 2.1 g). Subjects received treatment with lixisenatide or placebo for 6 weeks in random order, with a 4-week washout period in between. After 6 weeks of treatment, subjects underwent a two-step hyperinsulinemic hypoglycemic clamp at 3.5 and 2.8 mmol/L. After 6 weeks of treatment, HbA1c and FBG levels were lower after lixisenatide therapy than after placebo therapy. At the hypoglycemic level of 3.5 mmol/L, glucagon and epinephrine levels were significantly lower during lixisenatide treatment than during placebo treatment, whereas at 2.8 mmol/L glucagon and epinephrine levels did not differ between the subjects. Cortisol, pancreatic polypeptide, and norepinephrine levels did not differ significantly between the treatments. Glucagon and epinephrine levels are reduced by lixisenatide at a concentration of 3.5 mmol/L, but their counterregulatory responses to deep hypoglycemia at a concentration of 2.8 mmol/L are sustained during treatment with lixisenatide in combination with basal insulin. © 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

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Recognition and management of hyperinsulinemic hypoglycemia after bariatric surgery.

    Science.gov (United States)

    Malik, Sarah; Mitchell, James E; Steffen, Kristine; Engel, Scott; Wiisanen, Ron; Garcia, Luis; Malik, Shahbaz Ali

    2016-01-01

    Hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass (RYGB) due to the changes in gut hormonal milieu. Physicians should be aware of this complication to ensure timely and effective treatment of post-RYGB patients, who present to them with hypoglycemic symptoms. Possible causes of hypoglycemia in these patients include late dumping syndrome, nesidioblastosis and rarely insulinoma. Systematic evaluation including history, biochemical analysis, and diagnostic testing might help in distinguishing among these diagnoses. Continuous glucose monitoring is also a valuable tool, revealing the episodes in the natural environment and can also be used to monitor treatment success. Treatment should begin with strict low carbohydrate diet, followed by medication therapy. Therapy with diazoxide, acarbose, calcium channel blockers and octreotide have been proven to be beneficial, but the response apparently is highly variable. When other treatment options fail, surgical options can be considered. Copyright © 2015. Published by Elsevier Ltd.

  12. [Neonatal cholestasis and hypoglycemia like form of congenital hypopituitarism presentation].

    Science.gov (United States)

    Machado, Maren K; Bernardini, Alejandra; Giachetto, Gustavo

    2011-06-01

    Congenital hypopituitarism is a rare disease, of variable clinic. The neonatal hypoglycemia is one of the habitual forms of presentation; the cholestasis is a rare symptom of this disease. This is the case of a 2-months-old infant hospitalized for cholestatic jaundice. He added repeated episodes of severe hypoglycemia. We investigated metabolic and endocrine causes. The etiology was clarified by obtaining a critical sample that demonstrated the counterregulatory hormone deficiency. The diagnosis of congenital hypopituitarism was completed with confirmation of thyroid hormone and growth hormone deficiencies. It was confirmed the neuro-anatomical defect of “syndrome of pituitary stalk section” determined by pituitary stalk agenesis, pituitary hipoplasia, and ectopic neurohypophysis. Hormone replacement therapy was started with good response and outcome.

  13. Raspberry Leaf and Hypoglycemia in Gestational Diabetes Mellitus.

    Science.gov (United States)

    Cheang, Kai I; Nguyen, Thanh T; Karjane, Nicole W; Salley, Kelsey E S

    2016-12-01

    Raspberry leaf is commonly consumed by pregnant women. Hypoglycemic effects have been documented with other species within the plant family. Whether raspberry leaf affects glycemic control in gestational diabetes mellitus (GDM) is unknown. A 38-year-old nulliparous woman with GDM developed hypoglycemia requiring lowered insulin dose after consuming raspberry leaf tea at 32 weeks of gestation. The temporal relationship was confirmed by the patient's self-withdrawal and reintroduction of the herb. Fetal surveillance and growth were reassuring. A cesarean delivery was performed at 39 weeks of gestation. The neonate did not experience hypoglycemia or other complications. Placental biopsy revealed normal findings. Consumption of raspberry leaf may lead to reduced insulin requirements in GDM. Women with GDM should be cautioned about its use and their glucose levels more closely monitored.

  14. Insulinoma: A rare cause of hypoglycemia in a young female

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  17. Starvation of cancer via induced ketogenesis and severe hypoglycemia.

    Science.gov (United States)

    Kapelner, Adam; Vorsanger, Matthew

    2015-03-01

    Neoplasms are highly dependent on glucose as their substrate for energy production and are generally not able to catabolize other fuel sources such as ketones and fatty acids. Thus, removing access to glucose has the potential to starve cancer cells and induce apoptosis. Unfortunately, other body tissues are also dependent on glucose for energy under normal conditions. However, in human starvation (or in the setting of diet-induced ketogenesis), the body "keto-adapts" and glucose requirements of most tissues drop to almost nil. Exceptions include the central nervous system (CNS) and various other tissues which have a small but obligatory requirement of glucose. Our hypothesized treatment takes keto-adaptation as a prerequisite. We then propose the induction of severe hypoglycemia by depressing gluconeogenesis while administering glucose to the brain. Although severe hypoglycemia normally produces adverse effects such as seizure and coma, it is relatively safe following keto-adaptation. We hypothesize that our therapeutic hypoglycemia treatment has potential to rapidly induce tumor cell necrosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Hypoglycemia Following Bariatric Surgery: Our 31-Year Experience.

    Science.gov (United States)

    Michaels, Alex D; Hunter Mehaffey, J; Brenton French, W; Schirmer, Bruce D; Kirby, Jennifer L; Hallowell, Peter T

    2017-12-01

    The purposes of this study are to identify the cumulative incidence of post-bariatric surgery hypoglycemia (PBSH), describe its symptomatology, and characterize treatment patterns at a large academic institution. All patients who underwent bariatric surgery at a single institution from 1985 to 2015 were identified using a clinical database, administrative billing data identified patients who were treated for hypoglycemia, and chart reviews were performed to make a diagnosis of PBSH based on Whipple's triad. PBSH cases were reviewed including patient diabetes history, symptomatology, and treatment measures. Univariate analyses were performed to identify correlations based on symptomatology, laboratory values, and treatments utilized. Ninety (2.6%) of 3487 patients were diagnosed with PBSH with preoperative median age of 43 years, mean BMI of 50.0 kg/m 2 , and median glycated hemoglobin of 6.0%. Median time-to-first hypoglycemic event was 40.6 months. No factors were identified which predict symptom severity or resolution. The 24 (27%) patients who received pharmacotherapy to treat hypoglycemia were younger, had lower nadir blood glucose levels, and more frequent symptoms. Sixty-nine (79%) cases eventually resolved. PBSH onset and severity are highly variable. Successful management of these patients can prove difficult and should include dietary therapy, the selective use of pharmacotherapy and surgery, and the use of a multidisciplinary team including bariatric surgeons and endocrinologists.

  19. Social vulnerability and hypoglycemia among patients with diabetes.

    Science.gov (United States)

    Waitman, Jorge; Caeiro, Gabriela; Romero Gonzalez, Silvana A; Ré, Danila P; Daghero, Andrea; Gonzalez, Claudio D; Umpierrez, Guillermo E

    2017-02-01

    Lower-income populations are hit harder by the diabetes epidemic as regards both prevalence and the risk of complications. Food Insecurity is one of the mechanisms through which poverty may predispose people with low socio-economic status to poorer control and higher complication rates. The United Nations Food and Agriculture Organization defined food security as "the right to have access to sufficient nutritional and culturally acceptable food choices." Adults suffering from diabetes with limited income have a 40% greater chance of having food insecurity and an inadequate blood glucose control. Such patients have a two-fold greater risk of developing severe hypoglycemia. In addition, several studies have shown that social vulnerability resulting from food insecurity, low socioeconomic status, low educational levels, and poor health education is an independent risk factor for hypoglycemia, even after conventional predictors are controlled. This review analyzes the literature available on social vulnerability as a non-conventional risk factor for development of hypoglycemia in diabetic subjects. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    Science.gov (United States)

    Lopez, Janice Ms; Annunziata, Kathy; Bailey, Robert A; Rupnow, Marcia Ft; Morisky, Donald E

    2014-01-01

    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. 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. 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 Physical and Mental Summary scores were significantly lower for the recent hypoglycemia and nonrecent hypoglycemia groups compared with the never hypoglycemia group. Hypoglycemia can negatively impact many aspects of life. Greater awareness of those who are at risk for developing hypoglycemia can lead to the

  1. A Novel Algorithm in the Management of Hypoglycemia in Newborns

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. Influence of GLP-1 on myocardial glucose metabolism in healthy men during normo- or hypoglycemia

    DEFF Research Database (Denmark)

    Gejl, Michael; Lerche, Susanne; Mengel, Annette

    2014-01-01

    ) = 0.64, respectively) and changes in MGU correlated positively with the level of insulin resistance (HOMA 2IR) during hypoglycemia, P = 0.04, r(2) = 0.54. GLP-1 mediated an increase in circulating glucagon levels at PG levels below 3.5 mM and increased glucose infusion rates during the hypoglycemia....... GLP-1 preserves MGU during hypoglycemia in insulin resistant subjects. ClinicalTrials.gov registration numbers: NCT00418288: (hypoglycemia) and NCT00256256: (normoglycemia)....

  5. Risk of cardiac arrhythmias during hypoglycemia in patients with type 2 diabetes and cardiovascular risk.

    Science.gov (United States)

    Chow, Elaine; Bernjak, Alan; Williams, Scott; Fawdry, Robert A; Hibbert, Steve; Freeman, Jenny; Sheridan, Paul J; Heller, Simon R

    2014-05-01

    Recent trials of intensive glycemic control suggest a possible link between hypoglycemia and excess cardiovascular mortality in patients with type 2 diabetes. Hypoglycemia might cause arrhythmias through effects on cardiac repolarization and changes in cardiac autonomic activity. Our aim was to study the risk of arrhythmias during spontaneous hypoglycemia in type 2 diabetic patients with cardiovascular risk. Twenty-five insulin-treated patients with type 2 diabetes and a history of cardiovascular disease or two or more risk factors underwent simultaneous continuous interstitial glucose and ambulatory electrocardiogram monitoring. Frequency of arrhythmias, heart rate variability, and markers of cardiac repolarization were compared between hypoglycemia and euglycemia and between hyperglycemia and euglycemia matched for time of day. There were 134 h of recording at hypoglycemia, 65 h at hyperglycemia, and 1,258 h at euglycemia. Bradycardia and atrial and ventricular ectopic counts were significantly higher during nocturnal hypoglycemia compared with euglycemia. Arrhythmias were more frequent during nocturnal versus daytime hypoglycemia. Excessive compensatory vagal activation after the counterregulatory phase may account for bradycardia and associated arrhythmias. QT intervals, corrected for heart rate, >500 ms and abnormal T-wave morphology were observed during hypoglycemia in some participants. Hypoglycemia, frequently asymptomatic and prolonged, may increase the risk of arrhythmias in patients with type 2 diabetes and high cardiovascular risk. This is a plausible mechanism that could contribute to increased cardiovascular mortality during intensive glycemic therapy.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Histological and morphometric lesions in the pre-clinical, developmental phase of insulin-induced laminitis in Standardbred horses.

    Science.gov (United States)

    de Laat, Melody A; Patterson-Kane, Janet C; Pollitt, Christopher C; Sillence, Martin N; McGowan, Catherine M

    2013-03-01

    Lamellar pathology in experimentally-induced equine laminitis associated with euglycaemic hyperinsulinaemia is substantial by the acute, clinical phase (∼48h post-induction). However, lamellar pathology of the developmental, pre-clinical phase requires evaluation. The aim of this study was to analyse lamellar lesions both qualitatively and quantitatively, 6, 12 and 24h after the commencement of hyperinsulinaemia. Histological and histomorphometrical analyses of lamellar pathology at each time-point included assessment of lamellar length and width, epidermal cell proliferation and death, basement membrane (BM) pathology and leucocyte infiltration. Archived lamellar tissue from control horses and those with acute, insulin-induced laminitis (48h) was also assessed for cellular proliferative activity by counting the number of cells showing positive nuclear immuno labelling for TPX2. Decreased secondary epidermal lamellar (SEL) width and increased histomorphological evidence of SEL epidermal basal (and supra-basal) cell death occurred early in disease progression (6h). Increased cellular proliferation in SELs, infiltration of the dermis with small numbers of leucocytes and BM damage occurred later (24 and 48h). Some lesions, such as narrowing of the SELs, were progressive over this time period (6-48h). Cellular pathology preceded leucocyte infiltration and BM pathology, indicating that the latter changes may be secondary or downstream events in hyperinsulinaemic laminitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Gluconeogenesis and ketogenesis in perfused liver of rats submitted to short-term insulin-induced hypoglycaemia.

    Science.gov (United States)

    Albuquerque, G G; Gazola, V A F G; Garcia, R F; Souza, K L A; Barrena, H C; Curi, R; Bazotte, R B

    2008-01-01

    Gluconeogenesis and ketogenesis of in situ rat perfused liver submitted to short-term insulin-induced hypoglycaemia (IIH) were investigated. For this purpose, 24-h fasted rats that received intraperitoneal (ip) regular insulin (1.0 U kg(-1)) or saline were compared. The studies were performed 30 min after insulin (IIH group) or saline (COG group) injection. For gluconeogenesis studies, livers from the IIH and COG groups were perfused with increasing concentrations (from basal blood concentrations until saturating concentration) of glycerol, L-lactate (Lac) or pyruvate (Pyr). Livers of the IIH group showed maintained efficiency to produce glucose from glycerol and higher efficiency to produce glucose from Lac and Pyr. In agreement with these results the oral administration of glycerol (100 mg kg(-1)), Lac (100 mg kg(-1)), Pyr (100 mg kg(-1)) or glycerol (100 mg kg(-1)) + Lac (100 mg kg(-1)) + Pyr (100 mg kg(-1)) promoted glycaemia recovery. It can be inferred that the increased portal availability of Lac, Pyr and glycerol could help glycaemia recovery by a mechanism mediated, partly at least, by a maintained (glycerol) or increased (Lac and Pyr) hepatic efficiency to produce glucose. Moreover, in spite of the fact that insulin inhibits ketogenesis, the capacity of the liver to produce ketone bodies from octanoate during IIH was maintained. Copyright 2007 John Wiley & Sons, Ltd.

  9. Analysis of induction mechanisms of an insulin-inducible transcription factor SHARP-2 gene by (-)-epigallocatechin-3-gallate.

    Science.gov (United States)

    Haneishi, Ayumi; Takagi, Katsuhiro; Asano, Kosuke; Nakamura, Soichiro; Yamada, Kazuya

    2012-10-03

    The rat enhancer of split- and hairy-related protein-2 (SHARP-2) is an insulin-inducible transcription factor. In this study, we examined the mechanism(s) involved in the regulation of the rat SHARP-2 gene expression by (-)-epigallocatechin-3-gallate (EGCG). The induction of SHARP-2 mRNA by EGCG was repressed by pretreatments with inhibitors for either phosphoinositide 3-kinase (PI3K) or RNA polymerase II. Then, we examined a biological relationship between EGCG and transcription factor NF-κB interfering with the insulin action. The protein levels of the NF-κB were rapidly decreased by an EGCG treatment. Finally, the mechanism(s) of transcriptional activation of the rat SHARP-2 gene by both NF-κB and EGCG was analyzed. While overexpression of the NF-κB p65 protein decreased the promoter activity of the SHARP-2 gene, EGCG did not affect it. Thus, we conclude that EGCG induces the expression of the rat SHARP-2 gene via both the PI3K pathway and degradation of the NF-κB p65 protein.

  10. Is testing for postprandial hyperinsulinemic hypoglycemia after gastric bypass necessary?

    Science.gov (United States)

    Gasser, Michèle; Meier, Claudia; Herren, Sylvia; Aubry, Emilie; Steffen, Rudolf; Stanga, Zeno

    2017-11-23

    Postprandial hyperinsulinemic hypoglycemia (pHH) is an increasingly reported complication after Roux-en-Y gastric bypass (RYGB). As pHH can cause life-threatening emergencies if occurring without warning symptoms, challenge testing may detect patients at risk. The study objective was to determine the frequency of occurrence of pHH with or without symptoms of hypoglycemia after RYGB. We undertook an observational cohort study of consecutive, unselected patients approximately one year after uncomplicated RYGB. To simulate normal habits, all patients received a standardized carbohydrate-rich solid mixed meal. Plasma glucose and insulin were measured at 30, 60, 90, 120, and 150 min thereafter. Symptoms were classified as autonomous or neuroglycopenic. Patients with hypoglycemia (plasma glucose meal. 113 patients were included. Total weight loss at the first follow-up check (14 ± 0.4 months) was 33.97 ± 9.3%. After the carbohydrate-rich meal, glucose dropped to meal. The pHH occurred in 11.5% (n = 13) of patients. Asymptomatic patients (5.3%, n = 6) carried an increased risk (p = 0.008) for pHH. One patient needed emergency treatment after sudden loss of consciousness after the carbohydrate-rich meal. The occurrence of pHH was quite high in our study population with 11.5% thereof 5.3% asymptomatic. We therefore suggest that detection of these patients warrants a screening of patients after RYGB. At-risk patients should than be adequately advised to avoid carbohydrate-rich meals in order to optimize risk management. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  11. Insulin induced alteration in post-translational modifications of histone H3 under a hyperglycemic condition in L6 skeletal muscle myoblasts.

    Science.gov (United States)

    Kabra, Dhiraj G; Gupta, Jeena; Tikoo, Kulbhushan

    2009-06-01

    Chromatin remodelling events, especially histone modifications are proposed to form the mainstay for most of the biological processes. However, the role of these histone modifications in the progression of diabetes is still unknown. Hyperglycemia plays a major role in diabetes and its complications. The present study was undertaken to check the effect of insulin on alterations in post-translational modifications of histone H3 in L6 myoblasts under a hyperglycemic condition. We provide first evidence that insulin under hyperglycemic condition alters multiple histone modifications by enhanced production of reactive oxygen species. Insulin induces dose dependent changes in Lysine 4 and 9 methylation, Ser 10 phosphorylation and acetylation of histone H3. Interestingly, insulin induced generation of reactive oxygen species induces dephosphorylation and deacetylation of histone H3. Preincubation with catalase and DPI prevents these changes in post-translational modifications of histone H3. Furthermore, changes in histone H3 phosphorylation was found to be independent of ERK, p38, RSK2 and MSK1. Moreover, serine/threonine phosphatase inhibitor, okadaic acid attenuates insulin induced dephosphorylation and deacetylation of histone H3, suggesting a role of serine/threonine phosphatases in altering modifications of histone H3. These changes in epigenetic modifications can provide new insights into pathogenesis of diabetes.

  12. Review of Hypoglycemia in the Older Adult: Clinical Implications and Management.

    Science.gov (United States)

    Sircar, Mousumi; Bhatia, Ashmeet; Munshi, Medha

    2016-02-01

    The aging of the population is a worldwide phenomenon. The prevalence of diabetes rises with increasing age, so the personal and financial costs of diabetes in the aging population have become significant burdens. In 2012, 104 billion (59%) of the estimated $176 billion in United States healthcare expenditures attributable to diabetes were utilized by patients older than 65 years of age [American Diabetes Association (1)]. With improvement in diabetes management and better glycemic control in the general population, there is an increase in the prevalence of hypoglycemia, which is the complication of the treatment of diabetes. Older adults with diabetes have a higher risk for hypoglycemia due to altered adaptive physiologic responses to low glucose levels. These patients also have comorbidities, such as cognitive and functional loss, that interfere with prompt identification and/or appropriate treatment of hypoglycemia. Older adults who suffer from hypoglycemia also have increased risk for falls, fall-related fractures, seizures and comas and exacerbation of chronic conditions, such as cognitive dysfunction and cardiac events. Thus, hypoglycemia in the older adult must be proactively avoided to decrease significant morbidity and mortality. Education of the patients and caregivers is important in prevention and treatment of hypoglycemia. In this article, we discuss the important aspects and unique challenges pertaining to hypoglycemia in older population. We also highlight the risks, consequences and prevention and management strategies for hypoglycemia that can be used by healthcare providers caring for older populations. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  13. Minimizing the risk of hypoglycemia in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Kushner P

    2010-04-01

    Full Text Available Pamela KushnerUniversity of California, Irvine College of Medicine, California, USAAbstract: Hypoglycemia is a major barrier to achieving glycemic goals in patients with diabetes. Both acute and chronically recurrent hypoglycemic events appear to have long-term consequences for patients with type 2 diabetes mellitus (T2DM. Chronically recurrent hypoglycemia may lead to an impairment of the counterregulatory system, with the potential for the development of hypoglycemia unawareness syndrome, increased severe hypoglycemia-associated hospitalization, and increased mortality. Hypoglycemic events may also have negative implications in cardiovascular disease and/or dementia. Avoidance of hypoglycemia by treating with appropriate, individualized regimens for patients with T2DM should be a primary focus of physicians. Utilizing traditional agents (eg, metformin and thiazolidinediones that do not promote hypoglycemia, in combination with newer agents such as dipeptidyl peptidase-4 inhibitors and incretin mimetics, could offer a therapeutic advantage when trying to help patients reach their hemoglobin A1c goal without the added risk of hypoglycemia.Keywords: hypoglycemia, type 2 diabetes mellitus, incretin, dipeptidyl peptidase-4 inhibitors, diabetes management

  14. Neurodevelopment after neonatal hypoglycemia: a systematic review and design of an optimal future study

    NARCIS (Netherlands)

    Boluyt, Nicole; van Kempen, Anne; Offringa, Martin

    2006-01-01

    OBJECTIVE: Our goal was to assess the effect of episodes of neonatal hypoglycemia on subsequent neurodevelopment. METHODS: We searched Medline and Embase for cohort studies on subsequent neurodevelopment after episodes of hypoglycemia in the first week of life. Reference lists of available studies

  15. 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

    BACKGROUND: The purpose of this study was to explore the possible difference in the electroencephalogram (EEG) pattern between euglycemia and hypoglycemia in children with type 1 diabetes (T1D) during daytime and during sleep. The aim is to develop a hypoglycemia alarm based on continuous EEG...... measurement and real-time signal processing. METHOD: Eight T1D patients aged 6-12 years were included. A hyperinsulinemic hypoglycemic clamp was performed to induce hypoglycemia both during daytime and during sleep. Continuous EEG monitoring was performed. For each patient, quantitative EEG (qEEG) measures...... in specific bands comparing hypoglycemia to euglycemia both during daytime and during sleep. In daytime the EEG-based algorithm identified hypoglycemia in all children on average at a blood glucose (BG) level of 2.5 ± 0.5 mmol/l and 18.4 (ranging from 0 to 55) minutes prior to blood glucose nadir. During...

  16. 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

    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...... 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......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...

  17. Gender-Specific Effect of -102G>A Polymorphism in Insulin Induced Gene 2 on Obesity in Chinese Children

    Directory of Open Access Journals (Sweden)

    Fang-Hong Liu

    2015-01-01

    Full Text Available Background. Insulin induced gene 2 (INSIG2 encodes a protein that has a biological effect on regulation of adipocyte metabolism and body weight. This study aimed to investigate the association of INSIG2 gene -102G>A polymorphism with obesity related phenotypes in Chinese children and test gender-specific effects. Methods. The 2,030 independent individuals aged from 7 to 18 years, including 705 obese cases and 1,325 nonobese controls, were recruited from local schools. We measured the obesity-related phenotypes and detected the serum lipids. We genotype -102G>A polymorphism by using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS. Results. In all individuals, we found that the GG/GA genotype of INSIG2 -102G>A polymorphism was associated with risk of severe obesity (OR = 1.62, 95% CI: 1.11–2.36, and P=0.012 under the dominant model. The association with severe obesity existed only in boys (OR = 1.91, 95% CI: 1.15–3.17, P=0.012. The GG/GA genotype of -102G>A polymorphism was also associated with higher waist circumference (β=2.61 cm, P=0.031 in boys. No similar association was found in girls. The polymorphism was not associated with other obesity-related phenotypes, neither in all individuals nor in gender-specific population. Conclusions. This study identified a gender-specific effect of INSIG2 -102G>A polymorphism on risk of severe obesity and waist circumference in Chinese boys.

  18. Acute insulin-induced elevations of circulating leptin and feeding inhibition in lean but not obese rats.

    Science.gov (United States)

    Singh, Kimberly A; Boozer, Carol N; Vasselli, Joseph R

    2005-08-01

    Insulin has been shown to stimulate leptin mRNA expression acutely in rat adipose tissue, but its short-term effects on circulating leptin levels, and subsequent feeding behavior, have not been well described. We used 11-mo-old female selectively bred obesity-resistant (OR) and obesity-prone (OP) Sprague-Dawley rats maintained on laboratory chow to investigate this question. At testing, body weights and basal leptin levels of the OP rats were significantly elevated compared with the OR rats. In the 3-h fasted state, injection of 2.0 U insulin/kg ip resulted in significant elevations of plasma leptin at 4 h postinjection in both OP and OR groups (hour 4, +2.50 and +5.98 ng/ml, respectively). In separate feeding tests with the same groups, intake of laboratory chow pellets was significantly inhibited during hours 2-4 after 2.0 U/kg of insulin in the OR (-80.1%, P < 0.05), but not in the OP group, compared with intake after saline injections. In feeding tests with palatable moderately high-fat pellets after 2.0 and 3.0 U insulin/kg ip, significant decreases between hours 2 and 4 in intake were seen in the OR group only (-41.0 and -68.3%, respectively). Thus feeding inhibition coincides with insulin-induced elevations of plasma leptin in lean but not obese Sprague-Dawley rats. Our data suggest that elevations of leptin within the physiological range may contribute to short-term inhibition of food intake in rats and that this process may be stimulated by feeding-related insulin release.

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

    Science.gov (United States)

    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.

  20. 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

  1. 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....... with IAsp than HI (P = 0.003 and P = 0.044, respectively), as were mean plasma glucose levels 90 min after breakfast (P = 0.044 and P = 0.001, respectively). Maternal safety profiles and pregnancy outcomes were similar between treatments. CONCLUSIONS: IAsp is at least as safe and effective as HI when used...

  2. Nationwide reduction in the frequency of severe hypoglycemia by half

    DEFF Research Database (Denmark)

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

    2015-01-01

    -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...... the rate by 1.6-fold (P = 0.003) versus pump treatment, whereas long-acting insulin analogues were comparable with pump treatment (P = 0.1485). We found no association of SH with glycemic control (P > 0.05). Conclusions: A nationwide halving in rates of severe hypoglycemia was observed during the study...

  3. QT Measurement and Heart Rate Correction during Hypoglycemia: Is There a Bias?

    Directory of Open Access Journals (Sweden)

    Toke Folke Christensen

    2010-01-01

    Full Text Available 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 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 prolongation at hypoglycemia for QTcB (42(6 ms; P<.001 and QTcF (35(6 ms; P<.001. The MA method showed prolongation at hypoglycemia for QTcB (7(2 ms, P<.05 but not QTcF. No difference in ECG variables between the types of insulin was observed. Discussion. The method for measuring the QT interval has a significant impact on the prolongation of QT during hypoglycemia. Heart rate correction may also influence the QT during hypoglycemia while the type of insulin is insignificant. Prolongation of QTc in this study did not reach pathologic values suggesting that QTc prolongation cannot fully explain the dead-in-bed syndrome.

  4. Evaluation of glycogen storage disease as a cause of ketotic hypoglycemia in children.

    Science.gov (United States)

    Brown, Laurie M; Corrado, Michelle M; van der Ende, Rixt M; Derks, Terry G J; Chen, Margaret A; Siegel, Sara; Hoyt, Kate; Correia, Catherine E; Lumpkin, Christopher; Flanagan, Theresa B; Carreras, Caroline T; Weinstein, David A

    2015-05-01

    Ketone formation is a normal response when hypoglycemia occurs. Since the majority of children with recurrent hypoglycemia cannot be diagnosed with a known endocrine or metabolic disorder on a critical sample, ketotic hypoglycemia has been described as the most common cause of low blood glucose concentrations in children. Critical samples, however, will miss the ketotic forms of glycogen storage disease (GSD), which present with elevated ketones, hypoglycemia, and normal hormonal concentrations. A total of 164 children (96 boys, 68 girls) were enrolled in the study. Prediction of pathogenicity of DNA changes using computer modeling confirmed pathology in 20 individuals [four GSD 0, two GSD VI, 12 GSD IX alpha, one GSD IX beta, one GSD IX gamma] (12%). Boys were most likely to have changes in the PHKA2 gene, consistent with GSD IX alpha, an X-linked disorder. Mutations in genes involved in glycogen synthesis and degradation were commonly found in children with idiopathic ketotic hypoglycemia. GSD IX is likely an unappreciated cause of ketotic hypoglycemia in children, while GSD 0 and VI are relatively uncommon. GSD IX alpha should particularly be considered in boys with unexplained hypoglycemia.

  5. Evaluation and management of diabetic and non-diabetic hypoglycemia in end-stage renal disease.

    Science.gov (United States)

    Gosmanov, Aidar R; Gosmanova, Elvira O; Kovesdy, Csaba P

    2016-01-01

    Patients with end-stage renal disease (ESRD) regardless of diabetes status are at increased risk of hypoglycemia with a resultant array of adverse clinical outcomes. Therefore, hypoglycemia should be thoroughly evaluated in ESRD patients. In diabetic dialysis patients, hypoglycemic agents and nutritional alterations can trigger hypoglycemia in the background of diminished gluconeogenesis, reduced insulin clearance by the kidney and improved insulin sensitivity following initiation of renal replacement therapy. Detailed evaluation of antidiabetic regimen and nutritional patterns, patient education on self-monitoring of blood glucose and/or referral to a diabetes specialist may reduce risk of subsequent hypoglycemia. In certain situations, it is important to recognize the possibility of non-diabetic causes of hypoglycemia in patients with diabetes and to avoid treating pseudo-hyperglycemia caused by glucose- non-specific glucometers in patients utilizing icodextrin-based solutions for peritoneal dialysis. Adrenal insufficiency, certain medications, malnutrition and/or infection are among the most common causes of hypoglycemia in non-diabetic ESRD patients, and they should be suspected after exclusion of inadvertent use of hypoglycemic agents. The goal of this review article is to summarize approaches and recommendations for the work up and treatment of hypoglycemia in ESRD. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. NOCTURNAL HYPOGLYCEMIA--THE MAIN INDICATION FOR INSULIN PUMP THERAPY IN ADULTHOOD.

    Science.gov (United States)

    Baretić, Maja; Kraljević, Ivana; Renar, Ivana Pavlić

    2016-03-01

    The aim was to determine which adult type 1 diabetic patient receiving multiple daily injection therapy is the most appropriate candidate for insulin pump therapy, while taking into consideration limited insulin pump affordability in Croatia. A total of 145 type 1 diabetic patients (52% diagnosed in adult age) were monitored at the Department of Endocrinology, Clinical Department of Internal Medicine, Zagreb University Hospital Center from 2009 to 2014. Twenty-one patients started insulin pump therapy in adulthood (seven men and 14 women, median age 27). Five patients had chronic complications (retinopathy in two, polyneuropathy in one, and both nephropathy and retinopathy in two patients). The median HbA1c at the initiation of pump therapy was 6.95% versus 6.5% after 1 year of pump therapy. Patients were stratified according to indications for insulin pump therapy (frequent and/or severe hypoglycemia, specific lifestyle, having not reached glycemic goals despite adherence/labile diabetes, and preconception). Patients could meet more than one criterion. Initially, the occurrence of hypoglycemia was analyzed by 6-day continuous glucose monitoring, while re-evaluation was done after collecting history data at 1 year ± 3 months. Initially, all patients had a median of 5 hypoglycemias/6 days (30% nocturnal) versus 1 hypoglycemia/6 days (without nocturnal) after 1 year. The Wilcoxon signed-rank test yielded a statistically significant difference in hypoglycemic events, nocturnal hypoglycemia and HbA1c. Patients commencing insulin pump therapy due to hypoglycemia initially had median HbA1c of 6.7% with 7 hypoglycemia/6 days (50% nocturnal). After one year, median HbA1c was 6% with 1 hypoglycemia/6 days (without nocturnal). In conclusion, the main indication for insulin pump therapy in adults is the frequency of hypoglycemia, especially nocturnal ones.

  8. Hypoglycemia does not change the threshold for arousal from sleep in adolescents with type 1 diabetes.

    Science.gov (United States)

    Ly, Trang T; Jones, Timothy W; Griffiths, Amanda; Dart, Julie; Davis, Elizabeth A; Stick, Stephen; Wilson, Andrew

    2012-02-01

    Nocturnal hypoglycemia is a significant problem for children and adolescents with type 1 diabetes. The counterregulatory hormone response to hypoglycemia is blunted in both patients with type 1 diabetes and healthy subjects during sleep. It is not known whether the threshold for arousal from sleep is also modified by hypoglycemia. To address this question we compared the acoustic arousal threshold from sleep during hypoglycemia and euglycemia in adolescents with type 1 diabetes. Adolescents with type 1 diabetes were studied on two occasions: under hypoglycemic and euglycemic conditions. During the hypoglycemia night, subjects underwent a hyperinsulinemic hypoglycemic clamp with nadir glucose level of 2.8 mmol/L. Hypoglycemia was initiated during stage 2 sleep and maintained during slow-wave sleep. During the euglycemia night, blood glucose was maintained at 5.5 mmol/L using the same clamp technique. The acoustic arousal threshold was determined during the first cycle of slow-wave sleep. Seven subjects (mean±SE, 14.2±0.8 years old, mean glycosylated hemoglobin 8.1±0.3%, duration of diagnosis 2.5±0.5 years) completed both study nights. Arousal was only noted during acoustic testing and did not occur during hypoglycemia alone. The acoustic arousal threshold during slow-wave sleep was similar under both conditions: 79±8 dB during euglycemia and 71±6 dB (P=0.353) during hypoglycemia. In adolescents with type 1 diabetes, hypoglycemia does not impair arousal from slow-wave sleep induced by an external auditory stimulus.

  9. 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 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 (Psnack, 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.

  10. Nonislet Cell Tumor Hypoglycemia in a Patient with Adrenal Cortical Carcinoma

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  12. Neonatal hyperinsulinemic hypoglycemia in a patient with 9p deletion syndrome

    DEFF Research Database (Denmark)

    Bayat, Allan; Kirchhoff, Maria; Madsen, Camilla Gøbel

    2018-01-01

    We report the clinical and neuroradiological findings in a young boy harboring the 9p deletion syndrome including the novel findings of thalamic infarction and germinal matrix haemorrhage and neonatal hyperinsulinemic hypoglycemia. Both the hypoglycemic events and the ventriculomegaly found...

  13. Reversible hyperinsulinemic hypoglycemia after gastric bypass: a consequence of altered nutrient delivery

    DEFF Research Database (Denmark)

    McLaughlin, Tracey; Peck, Marcia; Holst, Jens

    2010-01-01

    Severe hypoglycemia after Roux-en-Y gastric bypass surgery (RYGB) is an increasingly recognized condition, characterized by neuroglycopenia and inappropriately elevated insulin concentrations that occur primarily in the postprandial state. Both pathophysiology and treatment of this disorder remain...

  14. 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...

  15. Hypoglycemia Prevention and User Acceptance of an Insulin Pump System with Predictive Low Glucose Management

    DEFF Research Database (Denmark)

    Choudhary, Pratik; Olsen, Birthe S; Conget, Ignacio

    2016-01-01

    was avoided with this strategy, as well as to assess user acceptance of the system and its insulin management features. SUBJECTS AND METHODS: Forty subjects with type 1 diabetes used the system for 4 weeks. We retrospectively evaluated performance of the system, using downloaded pump and sensor data...... between paired SG and BG values was 10.9 ± 13.8%. Subjects felt confident using the system, agreed that it helped protect them from hypoglycemia, and wished to continue using it. CONCLUSIONS: Automatic insulin pump suspension as implemented in the MiniMed 640G system can help patients avoid hypoglycemia......BACKGROUND: The MiniMed 640G sensor-augmented insulin pump system (Medtronic, Inc., Northridge, CA) can automatically suspend insulin delivery in advance of predicted hypoglycemia and restart it upon recovery. The aims of this analysis were to determine the rate at which predicted hypoglycemia...

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

    Science.gov (United States)

    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.

  17. Reversible Adrenal Insufficiency in Three Patients With Post–Roux-en-Y Gastric Bypass Noninsulinoma Pancreatogenous Hypoglycemia Syndrome

    Directory of Open Access Journals (Sweden)

    Shelly Mathur MD

    2014-03-01

    Full Text Available Objective . Noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS is a disorder of endogenous hyperinsulinemia that is clinically distinguishable from insulinoma, with a greater preponderance after Roux-en-Y gastric bypass (RYBG. Hyperinsulinemic hypoglycemia can predispose to attenuation of counterregulatory hormone responses to hypoglycemia, and consequent suppression of the hypothalamic–pituitary–adrenal (HPA axis. This case series describes 3 individuals who were diagnosed with adrenal insufficiency (AI after undergoing RYGB, complicated by NIPHS. Methods . A retrospective chart review was performed for each individual. Chart review applied particular attention to the onset of hyperinsulinemic hypoglycemia following bariatric surgery and the dynamic testing leading to the diagnoses of NIPHS and AI. Results . In each case, reactive hypoglycemia ensued within months to years after RYGB. Cosyntropin stimulation testing confirmed the diagnosis of AI. Hydrocortisone therapy reduced the frequency and severity of hypoglycemia and was continued until successful medical and/or surgical management of hyperinsulinism occurred. Follow-up testing of the HPA axis demonstrated resolution of AI. In all cases, hydrocortisone therapy was finally discontinued without incident. Conclusion . We speculate that transient AI is a potential complication in patients who experience recurrent hyperinsulinemic hypoglycemia after RYGB. The putative mechanism for this observation may be attenuation of the HPA axis after prolonged exposure to severe, recurrent hypoglycemia. We conclude that biochemical screening for AI should be considered in individuals who develop post-RYGB hyperinsulinemic hypoglycemia. If AI is diagnosed, supportive treatment should be maintained until hyperinsulinemic hypoglycemia has been managed effectively.

  18. A Single Bout of High-Intensity Interval Training Reduces Awareness of Subsequent Hypoglycemia in Patients With Type 1 Diabetes.

    Science.gov (United States)

    Rooijackers, Hanne M; Wiegers, Evita C; van der Graaf, Marinette; Thijssen, Dick H; Kessels, Roy P C; Tack, Cees J; de Galan, Bastiaan E

    2017-07-01

    High-intensity interval training (HIIT) has gained increasing popularity in patients with diabetes. HIIT acutely increases plasma lactate levels. This may be important, since the administration of lactate during hypoglycemia suppresses symptoms and counterregulation while preserving cognitive function. We tested the hypothesis that, in the short term, HIIT reduces awareness of hypoglycemia and attenuates hypoglycemia-induced cognitive dysfunction. In a randomized crossover trial, patients with type 1 diabetes and normal awareness of hypoglycemia (NAH), patients with impaired awareness of hypoglycemia (IAH), and healthy participants ( n = 10 per group) underwent a hyperinsulinemic-hypoglycemic (2.6 mmol/L) clamp, either after a HIIT session or after seated rest. Compared with rest, HIIT reduced symptoms of hypoglycemia in patients with NAH but not in healthy participants or patients with IAH. HIIT attenuated hypoglycemia-induced cognitive dysfunction, which was mainly driven by changes in the NAH subgroup. HIIT suppressed cortisol and growth hormone responses, but not catecholamine responses to hypoglycemia. The present findings demonstrate that a single HIIT session rapidly reduces awareness of subsequent hypoglycemia in patients with type 1 diabetes and NAH, but does not in patients with IAH, and attenuates hypoglycemia-induced cognitive dysfunction. The role of exercise-induced lactate in mediating these effects, potentially serving as an alternative fuel for the brain, should be further explored. © 2017 by the American Diabetes Association.

  19. Octreotide therapy and restricted fetal growth: pregnancy in familial hyperinsulinemic hypoglycemia

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    Marianne Geilswijk

    2017-02-01

    Full Text Available Hypoglycemia during pregnancy can have serious health implications for both mother and fetus. Although not generally recommended in pregnancy, synthetic somatostatin analogues are used for the management of blood glucose levels in expectant hyperinsulinemic mothers. Recent reports suggest 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. During the second pregnancy with a viable fetus, blood glucose levels were managed through dietary intervention alone. Thus, the patient was advised to take small but frequent meals high in fiber and low in carbohydrates. Throughout pregnancy, no incidences of severe hypoglycemia occurred and fetal 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 pregnancy.

  20. 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

    2016-09-01

    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.

  1. Persistent hyperinsulinemic hypoglycemia of infancy in 38 children

    International Nuclear Information System (INIS)

    Bin-Abbas, Bassam S.; Al-Mulhim, Abdulmohsin N.; Sakati, Nadia A.; Al-Ashwal, Abdullah A.

    2003-01-01

    To describe the clinical, biochemical,radiological and electrophysiological features of 38 Saudi children with persistent hyperinsulinemic hypoglycemia(PHH) that have been followed sine 1983. Data from 38 patients followed at King Faisal Specialist Hospital,Riyadh, Kingdom of Saudi Arabia 1983-2002 were analyzed. PHH of infancy was diagnosed on the basis of high intravenous glucose requirement,high insulin to glucose ratio, negative urinary ketones and normal tandem mass spectrometry. Patients were assessed radiologically by brain magnetic resonance imaging and computerized tomography. Patients were severely hypoglycaemic and intolerance to fast hypoglycaemic convulsion was the most commonly presenting complaint. 18 patients were developmentally delayed and 14 of them had brain atrophy.All patients except 9 did not respond to medical treatment and had surgery. Four of the pancreatectomized patients developed diabetes and 2 had malabsorption. PHH of infancy is relatively common and serious disease in Saudi children. Early medical intervention is necessary to avoid neurological damage. Surgically and probably medically treated patients are at a high risk of developing diabetes that could be the natural outcome of this disease. (author)

  2. 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.

  3. Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea

    Directory of Open Access Journals (Sweden)

    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.

  4. Insulin induces a transcriptional activation of epiregulin, HB-EGF and amphiregulin, by a PI3K-dependent mechanism: identification of a specific insulin-responsive promoter element

    DEFF Research Database (Denmark)

    Ornskov, Dorthe; Nexo, Ebba; Sørensen, Boe Sandahl

    2007-01-01

    ) [D. Ornskov, E. Nexo, B.S. Sorensen, Insulin-induced proliferation of bladder cancer cells is mediated through activation of the epidermal growth factor system, FEBS J. 273 (2006) 5479-5489]. In the present paper, we have investigated the molecular mechanism leading to this insulin-induced expression......Previously we have shown that insulin-stimulation of RT4 bladder cancer cells leads to increased proliferation, which require HER1 activation, and is accompanied by increased mRNA expression of the EGF-ligands heparin-binding EGF-like growth factor (HB-EGF), amphiregulin (AR), and epiregulin (EPI...

  5. Severe Hypoglycemia Following Acute Aluminum Phosphide (Rice Tablet Poisoning; A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Omid Mehrpour

    2012-08-01

    Full Text Available Aluminum phosphide (AlP as 3 g tablet is widely used in Iran to protect stored food grains from pests. Hyperglycemia following its ingestion has been already reported in the recent years but severe hypoglycemia is uncommon. Here, we report a 19 year old male who attempted suicide with one tablet of AlP and demonstrated severe hypoglycemia. Despite restoration of blood glucose concentration to normal, he failed to respond to supportive treatment and died. The possible mechanisms leading to severe hypoglycemia are discussed. Though severe hypoglycemia is rare following AlP poisoning, physicians managing such patients should be aware of it.

  6. Severe hypoglycemia following acute aluminum phosphide (rice tablet) poisoning; a case report and review of the literature.

    Science.gov (United States)

    Mehrpour, Omid; Aghabiklooei, Abbas; Abdollahi, Mohammad; Singh, Surjit

    2012-01-01

    Aluminum phosphide (AlP) as 3 g tablet is widely used in Iran to protect stored food grains from pests. Hyperglycemia following its ingestion has been already reported in the recent years but severe hypoglycemia is uncommon. Here, we report a 19 year old male who attempted suicide with one tablet of AlP and demonstrated severe hypoglycemia. Despite restoration of blood glucose concentration to normal, he failed to respond to supportive treatment and died. The possible mechanisms leading to severe hypoglycemia are discussed. Though severe hypoglycemia is rare following AlP poisoning, physicians managing such patients should be aware of it.

  7. Short communication: Cow- and herd-level prevalence of hypoglycemia in hyperketonemic postpartum dairy cows.

    Science.gov (United States)

    Dubuc, J; Buczinski, S

    2018-02-07

    The objective of this study was to quantify the prevalence of hypoglycemia in hyperketonemic dairy cows during the early postpartum period. A prospective observational study was conducted in 100 dairy herds selected by convenience. Within all participating herds, 40 cows (or the entire herd if smaller than 40 cows) were enrolled in the study (total of 3,776 enrolled cows). Herds were visited every 2 wk by an animal health technician. Cows were bled from their coccygeal vessels once between 1 and 14 d in milk, and cow-side testing was performed for ketonemia and glycemia using a device validated in cattle (Precision Xtra, Abbott, Mississauga, ON, Canada). Hyperketonemia was defined as β-hydroxybutyrate ≥1.4 mmol/L, and hypoglycemia was defined as glucose ≤2.2 mmol/L. Descriptive statistics were computed at the cow and herd levels. The cow-level prevalence of hyperketonemia, hypoglycemia, and simultaneous hypoglycemia and hyperketonemia was 20.0% (757/3,776), 13.8% (642/3,776), and 6.2% (235/3,776), respectively. Within the subset of hyperketonemic cows only, the prevalence of hypoglycemia was 31.0% (235/757). At the herd level, the median prevalence was 17.5% (minimum: 5.0%, first quartile: 10.0%, third quartile: 22.5%, maximum: 77.5%) for hyperketonemia, 15.0% (minimum: 5.0%, first quartile: 12.5%, third quartile: 20.0%, maximum: 47.5%) for hypoglycemia, and 7.5% (minimum: 2.5%, first quartile: 5.0%, third quartile: 12.5%, maximum: 17.5%) for simultaneous hypoglycemia and hyperketonemia. The herd-level median prevalence of hypoglycemia within the subset of hyperketonemic cows only was 30.6% (minimum: 2.5%, first quartile: 20.0%, third quartile: 39.1%, maximum: 63.0%). The results from this study show that the prevalence of simultaneous hyperketonemia and hypoglycemia is relatively low in the overall early postpartum cow population but also that approximately one third of hyperketonemic cows are hypoglycemic, which might represent an opportunity to improve

  8. Effects of subcutaneous, low-dose glucagon on insulin-induced mild hypoglycaemia in patients with insulin pump treated type 1 diabetes

    DEFF Research Database (Denmark)

    Ranjan, Ajenthen; Schmidt, S; Madsbad, Sten

    2016-01-01

    AIM: To investigate the dose-response relationship of subcutaneous glucagon administration on plasma glucose and on counterregulatory hormone responses during subcutaneous insulin induced mild hypoglycaemia in patients with type 1 diabetes treated with insulin pumps. MATERIALS AND METHODS: Eight...... insulin pump treated patients completed a blinded, randomized, placebo-controlled study. Hypoglycaemia was induced in the fasting state by a subcutaneous insulin bolus and when plasma glucose reached 3.4 mmol/l (95%CI 3.2-3.5), a subcutaneous bolus of either 100, 200, 300 µg glucagon or saline.......9(6.4-9.3) and 8.7(7.8-9.5) vs 3.6(3.4-3.9) mmol/l, p insulin levels. Area under plasma glucose curve, peak plasma glucose, time to peak and duration of plasma glucose above baseline...

  9. Mitochondrial 2,4-dienoyl-CoA reductase deficiency in mice results in severe hypoglycemia with stress intolerance and unimpaired ketogenesis.

    Science.gov (United States)

    Miinalainen, Ilkka J; Schmitz, Werner; Huotari, Anne; Autio, Kaija J; Soininen, Raija; Ver Loren van Themaat, Emiel; Baes, Myriam; Herzig, Karl-Heinz; Conzelmann, Ernst; Hiltunen, J Kalervo

    2009-07-01

    The mitochondrial beta-oxidation system is one of the central metabolic pathways of energy metabolism in mammals. Enzyme defects in this pathway cause fatty acid oxidation disorders. To elucidate the role of 2,4-dienoyl-CoA reductase (DECR) as an auxiliary enzyme in the mitochondrial beta-oxidation of unsaturated fatty acids, we created a DECR-deficient mouse line. In Decr(-/-) mice, the mitochondrial beta-oxidation of unsaturated fatty acids with double bonds is expected to halt at the level of trans-2, cis/trans-4-dienoyl-CoA intermediates. In line with this expectation, fasted Decr(-/-) mice displayed increased serum acylcarnitines, especially decadienoylcarnitine, a product of the incomplete oxidation of linoleic acid (C(18:2)), urinary excretion of unsaturated dicarboxylic acids, and hepatic steatosis, wherein unsaturated fatty acids accumulate in liver triacylglycerols. Metabolically challenged Decr(-/-) mice turned on ketogenesis, but unexpectedly developed hypoglycemia. Induced expression of peroxisomal beta-oxidation and microsomal omega-oxidation enzymes reflect the increased lipid load, whereas reduced mRNA levels of PGC-1alpha and CREB, as well as enzymes in the gluconeogenetic pathway, can contribute to stress-induced hypoglycemia. Furthermore, the thermogenic response was perturbed, as demonstrated by intolerance to acute cold exposure. This study highlights the necessity of DECR and the breakdown of unsaturated fatty acids in the transition of intermediary metabolism from the fed to the fasted state.

  10. Mitochondrial 2,4-dienoyl-CoA reductase deficiency in mice results in severe hypoglycemia with stress intolerance and unimpaired ketogenesis.

    Directory of Open Access Journals (Sweden)

    Ilkka J Miinalainen

    2009-07-01

    Full Text Available The mitochondrial beta-oxidation system is one of the central metabolic pathways of energy metabolism in mammals. Enzyme defects in this pathway cause fatty acid oxidation disorders. To elucidate the role of 2,4-dienoyl-CoA reductase (DECR as an auxiliary enzyme in the mitochondrial beta-oxidation of unsaturated fatty acids, we created a DECR-deficient mouse line. In Decr(-/- mice, the mitochondrial beta-oxidation of unsaturated fatty acids with double bonds is expected to halt at the level of trans-2, cis/trans-4-dienoyl-CoA intermediates. In line with this expectation, fasted Decr(-/- mice displayed increased serum acylcarnitines, especially decadienoylcarnitine, a product of the incomplete oxidation of linoleic acid (C(18:2, urinary excretion of unsaturated dicarboxylic acids, and hepatic steatosis, wherein unsaturated fatty acids accumulate in liver triacylglycerols. Metabolically challenged Decr(-/- mice turned on ketogenesis, but unexpectedly developed hypoglycemia. Induced expression of peroxisomal beta-oxidation and microsomal omega-oxidation enzymes reflect the increased lipid load, whereas reduced mRNA levels of PGC-1alpha and CREB, as well as enzymes in the gluconeogenetic pathway, can contribute to stress-induced hypoglycemia. Furthermore, the thermogenic response was perturbed, as demonstrated by intolerance to acute cold exposure. This study highlights the necessity of DECR and the breakdown of unsaturated fatty acids in the transition of intermediary metabolism from the fed to the fasted state.

  11. Identification of risk factors for suffering fear of hypoglycemia in type 1 Diabetes Mellitus patients.

    Science.gov (United States)

    Anarte, María Teresa; Carreira, Mónica; Machado, Alberto; Domínguez, Marta; Tapia, María José; Valdés, Sergio; Ruiz de Adana, María Soledad; Soriguer, Federico

    2014-12-01

    Hypoglycemia is one of the main burdens for type I Diabetes Mellitus (DM I) patients. The consequences of hypoglycemia can be quite unpleasant due to the variety of disagreeable physical and psychological symptoms it triggers. The patient's previous experience with hypoglycemia episodes will condition his psychological reaction to future episodes, promoting behavioral modifications that associate with poor glycemic control and worse prognosis, and even with developing psychological disorders, leading to fear of hypoglycemia (FH). To be able to provide tailored prevention and treatment of patients with FH it is necessary to identify the risk factors in DM I patients. We developed and validated the FH-15 scale, a novel instrument to assess FH, which showed good concurrent and predictive validity in DM I patients. In this work we aim to identify the risk factors for suffering FH by detecting DM I patients with FH using the FH-15 scale and then analyzing the association of clinical and sociodemographic variables. We found that age, needing help to resolve an episode of hypoglycemia, and a perceived lack of social support are risk factors for suffering FH. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  12. Post-Gastric Bypass Hyperinsulinemic Hypoglycemia: Fructose is a Carbohydrate Which Can Be Safely Consumed.

    Science.gov (United States)

    Bantle, Anne E; Wang, Qi; Bantle, John P

    2015-08-01

    Postprandial hypoglycemia after gastric bypass surgery is a serious problem. Available treatments are often ineffective. The objective was to test the hypotheses that injection of rapid-acting insulin before a high-carbohydrate meal or replacement of other carbohydrates with fructose in the meal would prevent hypoglycemia. This was a randomized, crossover trial comparing a high-carbohydrate meal with premeal saline injection (control), a high-carbohydrate meal with premeal insulin injection, and a high-fructose meal with total carbohydrate content similar to the control meal. The setting was an academic medical center. Ten patients with post-gastric bypass hyperinsulinemic hypoglycemia participated. Interventions included lispro insulin injected before test meals and replacement of other carbohydrates with fructose in test meals. The main outcome measure was plasma glucose meals. After the control meal, mean peak glucose and insulin were 173 ± 47 mg/dL and 134 ± 55 mU/L, respectively; mean glucose nadir was 44 ± 15 mg/dL; and eight of 10 subjects demonstrated glucose meal, mean peak postprandial glucose and insulin were 117 ± 20 mg/dL and 45 ± 31 mU/L, respectively (both P meal sweetened with fructose with little risk of hypoglycemia. Treatment with rapid-acting insulin before a carbohydrate-containing meal did not prevent hypoglycemia.

  13. The impact of parents' sleep quality and hypoglycemia worry on diabetes self-efficacy.

    Science.gov (United States)

    Herbert, Linda Jones; Monaghan, Maureen; Cogen, Fran; Streisand, Randi

    2015-01-01

    Parents of young children with type 1 diabetes (T1D) may experience poor sleep quality, possibly impacting their confidence in T1D management. This study investigated sleep characteristics among parents of children with T1D and relationships among parents' sleep quality, hypoglycemia worry, and diabetes self-efficacy. As part of baseline assessment for a randomized clinical trial (RCT) to promote parental management of T1D, 134 parents of children ≤ age 6 reported on demographics, parent sleep characteristics, hypoglycemia worry, and diabetes self-efficacy. Parents reported they slept less time than recommended by the National Sleep Foundation and endorsed greater global sleep problems than standardized norms of healthy adults; one third of parents reported their overall sleep quality was "fairly bad" or "very bad." Hypoglycemia worry and parents' sleep quality were both significantly related to diabetes self-efficacy, but parents' sleep quality did not mediate the relationship of hypoglycemia worry and diabetes self-efficacy. Many parents experience disrupted sleep that impacts their perceived ability to perform T1D management. Interventions designed to improve parental T1D self-efficacy should consider sleep and concerns about children's hypoglycemia.

  14. The Impact of Parents’ Sleep Quality and Hypoglycemia Worry on Diabetes Self-Efficacy

    Science.gov (United States)

    Herbert, Linda Jones; Monaghan, Maureen; Cogen, Fran; Streisand, Randi

    2014-01-01

    Parents of young children with type 1 diabetes (T1D) may experience poor sleep quality possibly impacting their confidence in T1D management. This study investigated sleep characteristics among parents of children with T1D and relationships amongst parents’ sleep quality, hypoglycemia worry, and diabetes self-efficacy. As part of baseline assessment for a randomized clinical trial (RCT) to promote parental management of T1D, 134 parents of children ≤ age 6 reported on demographics, parent sleep characteristics, hypoglycemia worry, and diabetes self-efficacy. Parents reported they slept less time than recommended by the National Sleep Foundation and endorsed greater global sleep problems than standardized norms of healthy adults; 1/3 of parents reported their overall sleep quality was “fairly bad” or “very bad.” Hypoglycemia worry and parents’ sleep quality were both significantly related to diabetes self-efficacy, but parents’ sleep quality did not mediate the relationship of hypoglycemia worry and diabetes self-efficacy. Many parents experience disrupted sleep that impacts their perceived ability to perform T1D management. Interventions designed to improve parental T1D self-efficacy should consider sleep and concerns about children’s hypoglycemia. PMID:24738994

  15. Hyperinsulinemic Hypoglycemia after Bariatric Surgery: Diagnosis and Management Experience from a Spanish Multicenter Registry

    Directory of Open Access Journals (Sweden)

    Nuria Vilarrasa

    2016-02-01

    Full Text Available Background: Severe postprandial hypoglycemia after bariatric surgery is a rare but invalidating complication. Our aim was to describe the different tests performed for its diagnosis and their outcomes as well as the response to the prescribed pharmacological and surgical treatments. Methods: Multicenter, retrospective systematic review of cases with recurrent severe postprandial hypoglycemia. Results: Over 11 years of follow-up, 22 patients were identified. The test most used to provoke hypoglycemia was the oral glucose load test followed by the mixed meal test which was the least standardized test. With pharmacological treatment, 3 patients were symptom-free (with octreotide and in 12 patients hypoglycemic episodes were attenuated. Seven patients had persistent hypoglycemic episodes and underwent surgery. Partial pancreatectomy was performed in 3 patients who had positive selective arterial calcium stimulation, and nesidioblastosis was confirmed in 2 patients. Reconversion to normal anatomy was performed in 3 patients, and 1 patient underwent a resection of the ‘candy cane' roux limb, with resolution of hypoglycemia in all cases. Conclusions: There is high heterogeneity in the evaluation and treatment options for postoperative hypoglycemia. In patients that do not respond to pharmacological treatment, reconstruction of gastrojejunal continuity may be the safest and most successful procedure.

  16. 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

  17. Glycogen storage disease type IX and growth hormone deficiency presenting as severe ketotic hypoglycemia.

    Science.gov (United States)

    Hodax, Juanita K; Uysal, Serife; Quintos, Jose Bernardo; Phornphutkul, Chanika

    2017-02-01

    Glycogen storage disease (GSD) type IX and growth hormone (GH) deficiency cause ketotic hypoglycemia via different mechanisms and are not known to be associated. We describe a patient presenting with severe ketotic hypoglycemia found to have both GSD IX and isolated GH deficiency. A 3-year-and-11-month-old boy with a history of prematurity, autism, developmental delay, seizures, and feeding difficulty was admitted for poor weight gain and symptomatic hypoglycemia. He was nondysmorphic, with a height of 93.8 cm (2%, -1.97 SDS), and has no hepatomegaly. He developed symptomatic hypoglycemia, with a serum glucose level of 37 mg/dL after 14 h of fasting challenge. Critical sample showed a GH of 0.24 ng/mL. GH provocative stimulation testing was done with a peak GH of 2.8 ng/mL. Brain magnetic resonance imaging showed a hypoplastic pituitary gland. Given the clinical symptoms, suspicion for mitochondrial disease was high. Dual Genome Panel by Massively Parallel Sequencing revealed a hemizygous variant c.721A>G (p1241V) in the X-linked PHKA2 gene, a causative gene for GSD IX. Red blood cell PhK enzyme activity testing was low, supporting the diagnosis. Given the patient's developmental delays that were not explained by GH deficiency alone, further investigation showed two unrelated conditions resulting in deranged metabolic adaptation to fasting leading to severe hypoglycemia.

  18. Utilization of the Zucker Diabetic Fatty (ZDF) Rat Model for Investigating Hypoglycemia-related Toxicities.

    Science.gov (United States)

    Tirmenstein, Mark; Horvath, Joseph; Graziano, Michael; Mangipudy, Raja; Dorr, Thomas; Colman, Karyn; Zinker, Bradley; Kirby, Mark; Cheng, Peter T W; Patrone, Laura; Kozlosky, John; Reilly, Timothy P; Wang, Victor; Janovitz, Evan

    2015-08-01

    Glucokinase (GK) catalyzes the initial step in glycolysis and is a key regulator of glucose homeostasis. Therefore, glucokinase activators (GKa) have potential benefit in treating type 2 diabetes. Administration of a Bristol-Myers Squibb GKa (BMS-820132) to healthy euglycemic Sprague-Dawley (SD) rats and beagle dogs in 1 mo toxicology studies resulted in marked and extended hypoglycemia with associated clinical signs of toxicity and degenerative histopathological changes in the stomach, sciatic nerve, myocardium, and skeletal muscles at exposures comparable to those expected at therapeutic clinical exposures. To investigate whether these adverse effects were secondary to exaggerated pharmacology (prolonged hypoglycemia), BMS-820132 was administered daily to male Zucker diabetic fatty (ZDF) rats for 1 mo. ZDF rats are markedly hyperglycemic and insulin resistant. BMS-820132 did not induce hypoglycemia, clinical signs of hypoglycemia, or any of the histopathologic adverse effects observed in the 1 mo toxicology studies at exposures that exceeded those observed in SD rats and dogs. This indicates that the toxicity observed in euglycemic animals was secondary to the exaggerated pharmacology of potent GK activation. This study indicates that ZDF rats, with conventional toxicity studies, are a useful disease model for testing antidiabetic agents and determining toxicities that are independent of prolonged hypoglycemia. © 2015 by The Author(s).

  19. Brain Glycogen Decreases During Intense Exercise Without Hypoglycemia: The Possible Involvement of Serotonin.

    Science.gov (United States)

    Matsui, Takashi; Soya, Shingo; Kawanaka, Kentaro; Soya, Hideaki

    2015-07-01

    Brain glycogen stored in astrocytes, a source of lactate as a neuronal energy source, decreases during prolonged exercise with hypoglycemia. However, brain glycogen dynamics during exercise without hypoglycemia remain unknown. Since intense exercise increases brain noradrenaline and serotonin as known inducers for brain glycogenolysis, we hypothesized that brain glycogen decreases with intense exercise not accompanied by hypoglycemia. To test this hypothesis, we employed a well-established acute intense exercise model of swimming in rats. Rats swam for fourteen 20 s bouts with a weight equal to 8 % of their body mass and were sacrificed using high-power (10 kW) microwave irradiation to inactivate brain enzymes for accurate detection of brain glycogen and monoamines. Intense exercise did not alter blood glucose, but did increase blood lactate levels. Immediately after exercise, brain glycogen decreased and brain lactate increased in the hippocampus, cerebellum, cortex, and brainstem. Simultaneously, serotonin turnover in the hippocampus and brainstem mutually increased and were associated with decreased brain glycogen. Intense swimming exercise that does not induce hypoglycemia decreases brain glycogen associated with increased brain lactate, implying an importance of glycogen in brain energetics during intense exercise even without hypoglycemia. Activated serotonergic regulation is a possible underlying mechanism for intense exercise-induced glycogenolysis at least in the hippocampus and brainstem.

  20. Rasagiline-induced severe recurrent hypoglycemia in a young woman without diabetes: a case report.

    Science.gov (United States)

    Ibrahim, Fawzi A Bachet; Rashid, Fauzia; Hussain, Azza A Bin; Alawadi, Fatheya; Bashier, A

    2017-02-02

    We report a case of a patient with recurrent severe hypoglycemia after initiating the drug rasagiline (Azilect) for Parkinson disease. A 25-year-old Emirati woman who had been diagnosed with Parkinson disease due to a genetic mutation since the age of 18 years presented to our hospital. She had been treated with a rotigotine patch 2 mg per day along with carbidopa + levodopa + entacapone 25 mg/100 mg/200 mg (Stalevo) over these years. Recently, her Stalevo had been changed to rasagiline (a monoamine oxidase B inhibitor). Soon after this change, she started experiencing recurrent documented severe hypoglycemia requiring hospitalization. Her hypoglycemic symptoms completely disappeared after 5-7 days of drug withdrawal. Despite detailed evaluation, no other causal relationship was documented except for rasagiline. To the best of our knowledge, this case report documents an unknown association between rasagiline and hypoglycemia.

  1. Hypoglycemia Alert Dogs: A Novel, Cost-effective Approach for Diabetes Monitoring?

    Science.gov (United States)

    Lippi, Giuseppe; Cervellin, Gianfranco; Dondi, Maurizio; Targher, Giovanni

    2016-11-01

    The recent publication of the results of 3 small trials, and as many as 5 case reports on dogs producing clear and intelligible alerts in the presence of their owners' hypoglycemia, opens an intriguing clinical scenario for management of diabetes. The skill seems attributable to the ability of dogs to identify patterns in skin and breath odors as well as to understand and interpret visual cues from humans during hypoglycemia. Provided that further trials can confirm the findings, the use of diabetes alert dogs that are trained to detect the onset of hypoglycemia can be regarded as a fast, versatile, reliable, and cost-effective approach for safeguarding the health of individuals with diabetes.

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

    DEFF Research Database (Denmark)

    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...... hypoglycemia have been described, we investigated the frequency of nocturnal hypoglycemia and the predictive value of bedtime blood glucose concentration for development of this condition in insulin treated diabetic patients. METHODS: During hospitalization, with no other changes in the patients' normal...... the night, caused by either discomfort or cannula problems. Of the remaining 43 patients, 16 (37%) had at least one blood glucose prevalence at 05 h. Only one patient felt hypoglycemic during the night. Hemoglobin A1c was similar...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    counterregulatory response. During the low cognitive load, rCBF decreased in response to hypoglycemia in a large bilateral area in the posterior part of the temporal lobe, and rCBF increased bilaterally in the anterior cingulate gyrus, the right frontal gyrus, the fusiform gyrus, thalamus, and the left inferior...... part of the frontal gyrus. During the high cognitive load, rCBF decreased bilaterally in a large region in the posterior part of the temporal gyrus and increased in the left and right anterior cingulate gyrus, left and right frontal gyrus, right parahippocampal and lingual gyrus, and left superior...... temporal gyrus. Visual impairment during hypoglycemia was associated with deactivation in the ventral visual stream. The anterior cingulate gyrus was activated during hypoglycemia in a load-dependent manner. Areas on the frontal convexity were differentially activated in response to the cognitive load...

  4. Real-time detection of nocturnal hypoglycemic episodes using a novel non-invasive hypoglycemia monitor.

    Science.gov (United States)

    Nguyen, Hung T; Ghevondian, Nejhdeh; Jones, Timothy W

    2009-01-01

    Hypoglycemia or low blood glucose is a common and serious side effect of insulin therapy in patients with diabetes. Hypoglycemia is unpleasant and can result in unconsciousness, seizures and even death. HypoMon is a realtime non-invasive monitor that measures relevant physiological parameters continuously to provide detection of hypoglycemic episodes in Type 1 diabetes mellitus patients (T1DM). Based on heart rate and corrected QT interval of the ECG signal, we have continued to develop effective algorithms for early detection of nocturnal hypoglycemia. From a clinical study of 24 children with T1DM, associated with natural occurrence of hypoglycemic episodes at night, their heart rates increased (1.021+/-0.264 vs. 1.068+/-0.314, PBayesian neural network which was derived from the training set with the highest log evidence, the estimated blood glucose profiles produced a significant correlation (P<0.02) against measured values in the test set.

  5. Methadone Use and the Risk of Hypoglycemia for Inpatients With Cancer Pain.

    Science.gov (United States)

    Flory, James H; Wiesenthal, Alison C; Thaler, Howard T; Koranteng, Lauren; Moryl, Natalie

    2016-01-01

    Methadone is an important drug in the management of both cancer-related and non-cancer-related pain and is the main pharmacologic agent used in the treatment of opioid addiction. Unexpected hypoglycemia has been observed in patients receiving methadone, prompting a more detailed investigation. To evaluate the incidence of hypoglycemia in a cohort of inpatients receiving methadone versus other opioids including fentanyl, hydromorphone, and morphine. Retrospective observational cohort of inpatients in a tertiary cancer center admitted for more than 48 hours from November 1, 2011 to October 30, 2013. The main outcomes were lowest measured daily blood glucose (in mg/dL) and incidence of hypoglycemia (defined as blood glucose methadone doses compared with other non-methadone opioids. Of the 641 eligible patients admitted during the study period who received at least one dose of methadone during admission, multivariable logistic regression showed significant associations between methadone and hypoglycemia at doses greater than 40 mg oral equivalents per day or with patient-controlled analgesia use. A dose-response relationship was observed, with an odds ratio of 3.1 (95% confidence interval 2.5, 3.6) when doses greater than 80 mg/day were used. No evidence of increased risk of hypoglycemia or of a dose-response curve was seen for the other opioids. The risk of hypoglycemia is increased for patients taking more than 40 mg oral methadone equivalents per day. When starting methadone at or more than 40 mg/day, we recommend blood glucose monitoring. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  6. Effect of bilateral carotid body resection on cardiac baroreflex control of blood pressure during hypoglycemia.

    Science.gov (United States)

    Limberg, Jacqueline K; Taylor, Jennifer L; Mozer, Michael T; Dube, Simmi; Basu, Ananda; Basu, Rita; Rizza, Robert A; Curry, Timothy B; Joyner, Michael J; Wehrwein, Erica A

    2015-06-01

    Hypoglycemia results in a reduction in cardiac baroreflex sensitivity and a shift in the baroreflex working range to higher heart rates. This effect is mediated, in part, by the carotid chemoreceptors. Therefore, we hypothesized hypoglycemia-mediated changes in baroreflex control of heart rate would be blunted in carotid body-resected patients when compared with healthy controls. Five patients with bilateral carotid body resection for glomus tumors and 10 healthy controls completed a 180-minute hyperinsulinemic, hypoglycemic (≈3.3 mmol/L) clamp. Changes in heart rate, blood pressure, and spontaneous cardiac baroreflex sensitivity were assessed. Baseline baroreflex sensitivity was not different between groups (P>0.05). Hypoglycemia resulted in a reduction in baroreflex sensitivity in both the groups (main effect of time, P<0.01) and responses were lower in resected patients when compared with controls (main effect of group, P<0.05). Hypoglycemia resulted in large reductions in systolic (-17±7 mm Hg) and mean (-14±5 mm Hg) blood pressure in resected patients that were not observed in controls (interaction of group and time, P<0.05). Despite lower blood pressures, increases in heart rate with hypoglycemia were blunted in resected patients (interaction of group and time, P<0.01). Major novel findings from this study demonstrate that intact carotid chemoreceptors are essential for increasing heart rate and maintaining arterial blood pressure during hypoglycemia in humans. These data support a contribution of the carotid chemoreceptors to blood pressure control and highlight the potential widespread effects of carotid body resection in humans. © 2015 American Heart Association, Inc.

  7. Sensor-Augmented Insulin Pumps and Hypoglycemia Prevention in Type 1 Diabetes

    DEFF Research Database (Denmark)

    Steineck, Isabelle; Ranjan, Ajenthen; Nørgaard, Kirsten

    2017-01-01

    prevention. We present evidence from randomized trials, observational studies, and meta-analyses including nonpregnant individuals with type 1 diabetes mellitus. We also outline concerns regarding SAPs with and without automated insulin suspension. There is evidence that SAP treatment reduces episodes......Hypoglycemia can lead to seizures, unconsciousness, or death. Insulin pump treatment reduces the frequency of severe hypoglycemia compared with multiple daily injections treatment. The addition of a continuous glucose monitor, so-called sensor-augmented pump (SAP) treatment, has the potential...

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

    Directory of Open Access Journals (Sweden)

    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

  9. Hypoglycemia-related information seeking among informal caregivers of type 2 diabetes patients: Implications for health education.

    Science.gov (United States)

    Reifegerste, Doreen; Hartleib, Sarah

    2016-06-01

    To examine information seeking and knowledge about hypoglycemia among partners and family of type 2 diabetes patients and to identify associations between information seeking, knowledge and demographic, and disease-related characteristics. Caregivers of adults with type 2 diabetes (N = 488) completed surveys assessing information seeking, knowledge of hypoglycemia symptoms and treatment, perceived competence, demographic information, and diabetes-related characteristics. Hierarchical and logistic regressions were used for data analysis. Nearly two thirds of family members and friends actively sought information about hypoglycemia, while health professionals and print media were reported as the main sources. Many respondents (74.5%) were able to identify at least one correct warning sign. But 32% could not state any correct treatment measures. Health professionals were the main and most helpful source of their knowledge. Education, past experience with hypoglycemia, and comprehension of information were associated with knowledge about treatment. Caregivers' perceived competence about hypoglycemia correlated with medical education, information-seeking, and comprehension of information. Our results indicate the importance of the hypoglycemia-related information seeking of caregivers in managing incidents of hypoglycemia. These findings suggest the need to consider caregivers' health knowledge when developing health education programs in diabetes care. More attention must be focused on providing interventions that motivate information seeking and improve the comprehension of information. Interventions should inform caregivers about hypoglycemia to enhance their knowledge.

  10. 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.

  11. 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

    on their suggested prevention strategies. RESULTS: We included 13 studies. Eight studies reported that ethanol, regardless of administration intravenously or orally, were associated with an increased risk of hypoglycemia due to decrease in plasma glucose, impaired counter-regulatory response, awareness...... of hypoglycemia and cognitive function. Five studies did not report an increased risk of hypoglycemia. None of the studies investigated prevention strategies for ethanol-induced hypoglycemia. Recommendations from 13 diabetes associations were included. All associations recommend combining ethanol with food intake...

  12. Intermediate algebra a textworkbook

    CERN Document Server

    McKeague, Charles P

    1985-01-01

    Intermediate Algebra: A Text/Workbook, Second Edition focuses on the principles, operations, and approaches involved in intermediate algebra. The publication first takes a look at basic properties and definitions, first-degree equations and inequalities, and exponents and polynomials. Discussions focus on properties of exponents, polynomials, sums, and differences, multiplication of polynomials, inequalities involving absolute value, word problems, first-degree inequalities, real numbers, opposites, reciprocals, and absolute value, and addition and subtraction of real numbers. The text then ex

  13. Intermediate algebra & analytic geometry

    CERN Document Server

    Gondin, William R

    1967-01-01

    Intermediate Algebra & Analytic Geometry Made Simple focuses on the principles, processes, calculations, and methodologies involved in intermediate algebra and analytic geometry. The publication first offers information on linear equations in two unknowns and variables, functions, and graphs. Discussions focus on graphic interpretations, explicit and implicit functions, first quadrant graphs, variables and functions, determinate and indeterminate systems, independent and dependent equations, and defective and redundant systems. The text then examines quadratic equations in one variable, system

  14. Acute Hypoglycemia Induces Painful Neuropathy and the Treatment of Coenzyme Q10

    Directory of Open Access Journals (Sweden)

    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.

  15. Treatment of Hypoglycemia in Adult Patients with Type 1 Diabetes: An Observational Study.

    Science.gov (United States)

    Savard, Valérie; Gingras, Véronique; Leroux, Catherine; Bertrand, Amélie; Desjardins, Katherine; Mircescu, Hortensia; Rabasa-Lhoret, Rémi

    2016-08-01

    1) To characterize the nutritional treatment of hypoglycemia in adult patients with type 1 diabetes mellitus and 2) to compare the characteristics of participants who follow the recommendations with the characteristics of those who do not. A total of 121 adults with type 1 diabetes were included in this cross-sectional analysis. Participants completed a food record and a glycemia and insulin doses logbook to collect data on mild to moderate hypoglycemic events (glycemia 20g of carbohydrates for correction. Self-administered questionnaires about fear of hypoglycemia were completed, and cardiometabolic profile variables were measured (glycated hemoglobin, blood pressure, lipid profile and body mass indexes). Of the 121 participants, 94 (78%) reported at least 1 hypoglycemic event, for a total of 271 events (2.2±2.1 episodes per patient). Of these events, 64% were treated within 15 minutes, and they were treated primarily with fruit juice or sweet beverages (39%) or mixed snacks (29%). Average carbohydrate intake for treatment was 32±24 grams. Of the participants, 73% overtreated their episodes. They were significantly younger and had greater fear of hypoglycemia than those who treated the episodes adequately. No difference was observed for cardiometabolic variables. The majority of patients in our cohort overtreated their hypoglycemic episodes. These results suggest that hypoglycemia-correction education needs to be reinforced. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  16. 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...

  17. 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 fr...

  18. 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/

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Optimal management of type 2 diabetes in patients with increased risk of hypoglycemia

    Directory of Open Access Journals (Sweden)

    Anderson M

    2014-03-01

    Full Text Available Morgan Anderson,1 Jason Powell,2 Kendall M Campbell,3 James R Taylor2 1North Florida/South Georgia Veterans Health System, Malcom Randall VAMC, 2University of Florida, College of Pharmacy, Gainesville, 3The Center for Underrepresented Minorities in Academic Medicine, The Florida State University College of Medicine Tallahassee, FL, USA Abstract: With the number of individuals diagnosed with type 2 diabetes on the rise, it has become more important to ensure these patients are effectively treated. The Centers for Disease Control and Prevention estimated that 8.3% of all Americans were diagnosed with diabetes in 2011 and this number will likely continue to rise. With lifestyle interventions, such as proper diet and exercise, continuing to be an essential component of diabetes treatment, more patients are requiring medication therapy to help them reach their therapeutic goals. It is important for the clinician, when determining the treatment strategy for these individuals, to find a balance between reaching treatment goals and limiting the adverse effects of the treatments themselves. Of all the adverse events associated with treatment of diabetes, the risk of hypoglycemia is one that most therapies have in common. This risk is often a limiting factor when attempting to aggressively treat diabetic patients. This manuscript will review how hypoglycemia is defined and categorized, as well as discuss the prevalence of hypoglycemia among the many different treatment options. Keywords: type 2 diabetes, hypoglycemia

  1. Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

    Directory of Open Access Journals (Sweden)

    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.

  2. Hypoglycemia in falciparum malaria: is fasting an unrecognized and insufficiently emphasized risk factor?

    NARCIS (Netherlands)

    Thien, Huynh V.; Kager, Piet A.; Sauerwein, Hans P.

    2006-01-01

    Hypoglycemia is a frequently encountered complication in falciparum malaria that is usually ascribed to increased glucose use and impaired glucose production caused by the inhibition of gluconeogenesis. Here, in light of recent data showing that glucose production and gluconeogenesis are often

  3. Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

    Directory of Open Access Journals (Sweden)

    Chih-Ting Su

    2016-11-01

    Full Text Available Insulin antibodies (IA associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA found in insulin autoimmune syndrome (IAS, which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%, high insulin concentration (111.9 IU/mL and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly.

  4. Effects of repetitive hypoglycemia on neuroendocrine response and brain tyrosine hydroxylase activity in the rat.

    NARCIS (Netherlands)

    Figlewicz, D. P.; Van Dijk, G.; Wilkinson, C. W.; Gronbeck, P.; Higgins, M.; Zavosh, A.

    2002-01-01

    Hypoglycemia-associated autonomic failure (HAAF) is a syndrome of acute adaptation to a metabolic stressor, in which neuroendocrine responses to repetitive hypoglycemic bouts are blunted. The CNS mechanisms that contribute to HAAF are unknown. In the present study, we modeled HAAF in the rat and

  5. 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...

  6. Interactions between hypoglycemia and sleep architecture in children with type 1 diabetes mellitus.

    Science.gov (United States)

    Pillar, Giora; Schuscheim, Guy; Weiss, Ram; Malhotra, Atul; McCowen, Karen C; Shlitner, Arie; Peled, Nir; Shehadeh, Naim

    2003-02-01

    To assess the interactions between nocturnal hypoglycemia and sleep in children with type 1 diabetes mellitus (DM). Children with DM (n = 15) and 15 matched control children underwent full night polysomnographic recordings. Blood glucose levels were measured in the diabetic children by means of the MiniMed Continuous Glucose Monitoring System. Six of the diabetic children were also studied by peripheral arterial tonometry (an indirect indicator of sympathetic responses). Five children with DM (33%) had profound nocturnal hypoglycemia, which was associated with increased sleep efficiency, increased slow wave sleep, and increased Delta power in spectral analysis of the electroencephalogram. Hypoglycemic episodes were not associated with sympathetic activation. Rapid decline in glucose levels (>25 mg/dL/hour) but not the absolute degree of hypoglycemia were associated with awakenings from sleep. We conclude that sleep may inhibit sympathetic and arousal response to hypoglycemia. Rapid changes in glucose levels, independent of absolute glucose levels, may result in awakening from sleep. Continuous measurement of glucose levels during sleep may add important features in the treatment of children with DM.

  7. KCNQ1 long QT syndrome patients have hyperinsulinemia and symptomatic hypoglycemia.

    Science.gov (United States)

    Torekov, Signe S; Iepsen, Eva; Christiansen, Michael; Linneberg, Allan; Pedersen, Oluf; Holst, Jens J; Kanters, Jørgen K; Hansen, Torben

    2014-04-01

    Patients with loss-of-function mutations in KCNQ1 have KCNQ1 long QT syndrome (LQTS). KCNQ1 encodes a voltage-gated K(+) channel located in both cardiomyocytes and pancreatic β-cells. Inhibition of KCNQ1 in β-cells increases insulin secretion. Therefore KCNQ1 LQTS patients may exhibit increased insulin secretion. Fourteen patients, from six families, diagnosed with KCNQ1 LQTS were individually matched to two randomly chosen BMI-, age-, and sex-matched control participants and underwent an oral glucose tolerance test (OGTT), a hypoglycemia questionnaire, and continuous glucose monitoring. KCNQ1 mutation carriers showed increased insulin release (area under the curve 45.6 ± 6.3 vs. 26.0 ± 2.8 min ⋅ nmol/L insulin) and β-cell glucose sensitivity and had lower levels of plasma glucose and serum potassium upon oral glucose stimulation and increased hypoglycemic symptoms. Prolonged OGTT in four available patients and matched control subjects revealed hypoglycemia in carriers after 210 min (range 1.4-3.6 vs. 4.1-5.3 mmol/L glucose), and 24-h glucose profiles showed that the patients spent 77 ± 18 min per 24 h in hypoglycemic states (KCNQ1 LQTS, caused by mutations in KCNQ1, includes, besides long QT, hyperinsulinemia, clinically relevant symptomatic reactive hypoglycemia, and low potassium after an oral glucose challenge, suggesting that KCNQ1 mutations may explain some cases of "essential" reactive hypoglycemia.

  8. Effectiveness of a nurse-managed protocol to prevent hypoglycemia in hospitalized patients with diabetes.

    Science.gov (United States)

    Marelli, Giuseppe; Avanzini, Fausto; Iacuitti, Giuseppe; Planca, Enrico; Frigerio, Ilaria; Busi, Giovanna; Carlino, Liliana; Cortesi, Laura; Roncaglioni, Maria Carla; Riva, Emma

    2015-01-01

    Hypoglycemia due to inadequate carbohydrate intake is a frequent complication of insulin treatment of diabetic in-patients. Objective. To assess the effectiveness of a nurse-managed protocol to prevent hypoglycemia during subcutaneous insulin treatment. Prospective pre-post-intervention study. In 350 consecutive diabetic in-patients the incidence of hypoglycemia (blood glucose food to integrate incomplete carbohydrate intake in the meal; (2) in case of lack of appetite or repeatedly partial intake of the planned food, prandial insulin administered at the end of the meal to be related to the actual amount of carbohydrates eaten; (3) intravenous infusion of glucose during prolonged fasting. Eighty-four patients in phase A and 266 in phase B received subcutaneous insulin for median periods of, respectively, 7 (Q1-Q3 6-12) and 6 days (Q1-Q3 4-9). Hypoglycemic events declined significantly from 0.34 ± 0.33 per day in phase A to 0.19 ± 0.30 in phase B (P > 0.001). A nurse-managed protocol focusing on carbohydrate intake reduced the incidence of hypoglycemia in patients with diabetes receiving subcutaneous insulin in hospital.

  9. The GOAT-Ghrelin System Is Not Essential for Hypoglycemia Prevention during Prolonged Calorie Restriction

    NARCIS (Netherlands)

    Yi, Chun-Xia; Heppner, Kristy M.; Kirchner, Henriette; Tong, Jenny; Bielohuby, Maximillian; Gaylinn, Bruce D.; Müller, Timo D.; Bartley, Erin; Davis, Harold W.; Zhao, Yongmei; Joseph, Anupama; Kruthaupt, Traci; Ottaway, Nickki; Kabra, Dhiraj; Habegger, Kirk M.; Benoit, Stephen C.; Bidlingmaier, Martin; Thorner, Michael O.; Perez-Tilve, Diego; Tschöp, Matthias H.; Pfluger, Paul T.

    2012-01-01

    Objective: 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

  10. 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/

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

    Directory of Open Access Journals (Sweden)

    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

  12. Insulin Delivery Into the Peripheral Circulation: A Key Contributor to Hypoglycemia in Type 1 Diabetes

    Science.gov (United States)

    Kraft, Guillaume; Scott, Melanie F.; Neal, Doss W.; Farmer, Ben; Smith, Marta S.; Hastings, Jon R.; Allen, Eric J.; Donahue, E. Patrick; Rivera, Noelia; Winnick, Jason J.; Edgerton, Dale S.; Nishimura, Erica; Fledelius, Christian; Brand, Christian L.; Cherrington, Alan D.

    2015-01-01

    Hypoglycemia limits optimal glycemic control in type 1 diabetes mellitus (T1DM), making novel strategies to mitigate it desirable. We hypothesized that portal (Po) vein insulin delivery would lessen hypoglycemia. In the conscious dog, insulin was infused into the hepatic Po vein or a peripheral (Pe) vein at a rate four times of basal. In protocol 1, a full counterregulatory response was allowed, whereas in protocol 2, glucagon was fixed at basal, mimicking the diminished α-cell response to hypoglycemia seen in T1DM. In protocol 1, glucose fell faster with Pe insulin than with Po insulin, reaching 56 ± 3 vs. 70 ± 6 mg/dL (P = 0.04) at 60 min. The change in area under the curve (ΔAUC) for glucagon was similar between Pe and Po, but the peak occurred earlier in Pe. The ΔAUC for epinephrine was greater with Pe than with Po (67 ± 17 vs. 36 ± 14 ng/mL/180 min). In protocol 2, glucose also fell more rapidly than in protocol 1 and fell faster in Pe than in Po, reaching 41 ± 3 vs. 67 ± 2 mg/dL (P < 0.01) by 60 min. Without a rise in glucagon, the epinephrine responses were much larger (ΔAUC of 204 ± 22 for Pe vs. 96 ± 29 ng/mL/180 min for Po). In summary, Pe insulin delivery exacerbates hypoglycemia, particularly in the presence of a diminished glucagon response. Po vein insulin delivery, or strategies that mimic it (i.e., liver-preferential insulin analogs), should therefore lessen hypoglycemia. PMID:26085570

  13. Increasing Trend in the Number of Severe Hypoglycemia Patients in Korea

    Directory of Open Access Journals (Sweden)

    Jin Taek Kim

    2011-04-01

    Full Text Available BackgroundTo investigate whether the number of subjects with severe hypoglycemia who are brought to a hospital emergency department is increasing and to identify whether there have been changes in the demographic and clinical characteristics of those subjects.MethodsWe analyzed data from the Emergency Departments of two general hospitals in Seoul, Korea. We included data from all adult subjects with type 2 diabetes who presented to an emergency department with severe hypoglycemia between January 1, 2004 and December 30, 2009.ResultsA total of 740 cases of severe hypoglycemia were identified. The mean subject age was 69±12 years, mean duration of diabetes was 13.8±9.3 years, and 53.2% of subjects were receiving insulin therapy. We observed a sharp rise in the number of cases between 2006 and 2007. Stages 3-5 chronic kidney disease was diagnosed in 31.5% of subjects, and low C-peptide levels (<0.6 ng/mL were found in 25.5%. The mean subject age, duration of diabetes, HbA1c level, and renal and insulin secretory function values did not change significantly during the study period. The proportion of glimepiride use increased, while use of gliclazide decreased among sulfonylurea users. Use of insulin analogues increased, while use of NPH/RI decreased among insulin users.ConclusionWe identified a sharp increase in the number of subjects with severe hypoglycemia presenting to an emergency room since 2006. The clinical characteristics of these subjects did not change markedly during the study period. Nationwide studies are warranted to further clarify this epidemic of severe hypoglycemia.

  14. The Use of Gastrostomy Tube for the Long-Term Remission of Hyperinsulinemic Hypoglycemia After Roux-en-y Gastric Bypass

    DEFF Research Database (Denmark)

    Craig, CM; Lamendola, C; Holst, Jens Juul

    2015-01-01

    Objective: Hyperinsulinemic hypoglycemia is an increasingly reported complication of Roux-en-Y gastric bypass surgery (RYGB), for which there is currently no acceptable treatment. We present a case of the reversal of severe hyperinsulinemic hypoglycemia through gastrostomy tube (GT) feeding to th...... as an effective and durable treatment for severe refractory hyperinsulinemic hypoglycemia after RYGB. (AACE Clinical Case Rep. 2015;1:e84-e87)......Objective: Hyperinsulinemic hypoglycemia is an increasingly reported complication of Roux-en-Y gastric bypass surgery (RYGB), for which there is currently no acceptable treatment. We present a case of the reversal of severe hyperinsulinemic hypoglycemia through gastrostomy tube (GT) feeding...

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

    Science.gov (United States)

    Malabu, Usman H; Vangaveti, Venkat N; Kennedy, Richard Lee

    2014-01-01

    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 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, the risk factors of falls associated with hypoglycemia in elderly diabetics were highlighted and management plans were suggested. A target hemoglobin A1c level between 7% and 8% seems to be more appropriate for this population. In addition, the first-choice drugs should have good safety profiles and have the lowest probability of causing hypoglycemia - such as metformin (in the absence of significant renal impairment) and incretin enhancers - while other therapies that may cause more frequent hypoglycemia should be avoided.

  16. [Hypoglycemia induced by a solitary fibrous tumor of the lung or Doege-Potter syndrome: Report of one case].

    Science.gov (United States)

    Soutelo, Jimena; Moldes, Sofía; Martin, Ayelén; Lutfi, Rubén; Leal Reyna, Mariela

    2016-01-01

    We report the case of a 75-year-old man who was admitted to the hospital with symptoms of severe hypoglycemia. He had a history of solitary fibrous tumor diagnosed by Pathology after its complete surgical resection eight years before. The laboratory examination reported hypoglycemia with inhibited Insulin secretion. A computed tomography of the thorax revealed a large solid heterogeneous mass in the left hemithorax. Solitary fibrous tumor is a rare neoplasm. The association of solitary fibrous tumor and paraneoplastic hypoglycemia is known as Doege-Potter syndrome and occurs in less than 5% of all solitary fibrous tumors.

  17. 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...... remain on how cardiovascular autonomic neuropathy (CAN) influences these measurable changes. This study aims to examine if changes in HRV during hypoglycemia are confounded by the presence of CAN. METHODS: Twenty-one adults (hereof 13 men) with T1D prone to hypoglycemia were recruited and monitored...

  18. Mobile communication and intermediality

    DEFF Research Database (Denmark)

    Helles, Rasmus

    2013-01-01

    The article argues the importance of intermediality as a concept for research in mobile communication and media. The constant availability of several, partially overlapping channels for communication (texting, calls, email, Facebook, etc.) requires that we adopt an integrated view of the various...

  19. an intermediate moisture meat

    African Journals Online (AJOL)

    Bunmi

    Matured leaves of Ocimum gratissimum were harvested and the extracts used to cure. Suya (an intermediate moisture meat). O. gratissimum leaves were collected from. Oyo state south west region of Nigeria, rinsed in distilled water and squeezed to extract the fluid. The meat used was Semi membranosus muscle from beef ...

  20. Bolus Calculator Reduces Hypoglycemia in the Short Term and Fear of Hypoglycemia in the Long Term in Subjects with Type 1 Diabetes (CBMDI Study).

    Science.gov (United States)

    Vallejo Mora, María Del Rosario; Carreira, Mónica; Anarte, María Teresa; Linares, Francisca; Olveira, Gabriel; González Romero, Stella

    2017-07-01

    In a previous study we demonstrated improvement in metabolic control and reduction in hypoglycemia in people with type 1 diabetes on multiple daily injections, after having used a bolus calculator for 4 months. To demonstrate whether (1) extending its use (2) or introducing it in the control group, previously subjected to treatment intensification, could further improve metabolic control and related psychological issues. After the previous clinical trial, in which the subjects were randomized either to treatment with the calculator or to control group for 4 months, both groups used the calculator during an additional 4-month period. In the previous control group, after using the device, HbA1c did not improve (7.86% ± 0.87% vs. 8.01% ± 0.93%, P 0.215), although a significant decrease in postprandial hypoglycemia was observed (2.3 ± 2 vs. 1.1 ± 1.2/2 weeks, P 0.002). In the group in which the treatment was extended from 4 to 8 months, HbA1c did not improve either (7.61 ± 0.58 vs. 7.73 ± 0.65, P 0.209); however this group had a greater perceived treatment satisfaction (12.03 ± 4.26 vs. 13.71 ± 3.75, P 0.007) and a significant decrease in fear of hypoglycemia (28.24 ± 8.18 basal vs. 25.66 ± 8.02 at 8 months, P 0.026). The extension in the use of the calculator or its introduction in a previously intensified control group did not improve metabolic control, although it did confirm a decrease in hypoglycemic episodes in the short term, while the extension of its use to 8 months was associated with a reduction in fear of hypoglycemia and greater treatment satisfaction.

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

    Directory of Open Access Journals (Sweden)

    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

  2. Recurrent hypoglycemia in a patient of neurofibromatosis type 1 and type 1 diabetes mellitus: Munchausen′s syndrome mimicking Insulinoma

    Directory of Open Access Journals (Sweden)

    Mubaraq Naqash

    2015-01-01

    Full Text Available A 35-year-old widow having neurofibromatosis type 1 (NF 1 and type 1 diabetes mellitus (DM was admitted for abdominal pain, vomiting and recent onset low blood sugars. During hospitalization, the patient developed recurrent episodes of hypoglycemia despite stopping insulin. A possibility of insulinoma was made due to the presence of abdominal pain, vomiting, hypoglycemia, and association of insulinoma with NF 1. However, surprisingly c-peptide was very low and plasma insulin levels were high. A detailed psychiatric evaluation of the patient revealed Munchausen′s syndrome as a cause of recurrent hypoglycemia. Unrecognized psychiatric illnesses in type 1 DM may lead to overzealous investigation. In conclusion, the clinical presentations of persons with factitious disorder are varied and impact every area of medicine, factitious causes should always be considered in unclarified recurrent hypoglycemia, especially in cases presented with dramatic but inconsistent medical history, and an unusual personal behavior.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Combining genetic algorithm and Levenberg-Marquardt algorithm in training neural network for hypoglycemia detection using EEG signals.

    Science.gov (United States)

    Nguyen, Lien B; Nguyen, Anh V; Ling, Sai Ho; Nguyen, Hung T

    2013-01-01

    Hypoglycemia is the most common but highly feared complication induced by the intensive insulin therapy in patients with type 1 diabetes mellitus (T1DM). Nocturnal hypoglycemia is dangerous because sleep obscures early symptoms and potentially leads to severe episodes which can cause seizure, coma, or even death. It is shown that the hypoglycemia onset induces early changes in electroencephalography (EEG) signals which can be detected non-invasively. In our research, EEG signals from five T1DM patients during an overnight clamp study were measured and analyzed. By applying a method of feature extraction using Fast Fourier Transform (FFT) and classification using neural networks, we establish that hypoglycemia can be detected efficiently using EEG signals from only two channels. This paper demonstrates that by implementing a training process of combining genetic algorithm and Levenberg-Marquardt algorithm, the classification results are improved markedly up to 75% sensitivity and 60% specificity on a separate testing set.

  5. 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

  6. The Intermediate Neutrino Program

    Energy Technology Data Exchange (ETDEWEB)

    Adams, C.; et al.

    2015-03-23

    The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program (WINP) at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop.

  7. The Intermediate Neutrino Program

    CERN Document Server

    Adams, C.; Ankowski, A.M.; Asaadi, J.A.; Ashenfelter, J.; Axani, S.N.; Babu, K.; Backhouse, C.; Band, H.R.; Barbeau, P.S.; Barros, N.; Bernstein, A.; Betancourt, M.; Bishai, M.; Blucher, E.; Bouffard, J.; Bowden, N.; Brice, S.; Bryan, C.; Camilleri, L.; Cao, J.; Carlson, J.; Carr, R.E.; Chatterjee, A.; Chen, M.; Chen, S.; Chiu, M.; Church, E.D.; Collar, J.I.; Collin, G.; Conrad, J.M.; Convery, M.R.; Cooper, R.L.; Cowen, D.; Davoudiasl, H.; de Gouvea, A.; Dean, D.J.; Deichert, G.; Descamps, F.; DeYoung, T.; Diwan, M.V.; Djurcic, Z.; Dolinski, M.J.; Dolph, J.; Donnelly, B.; Dwyer, D.A.; Dytman, S.; Efremenko, Y.; Everett, L.L.; Fava, A.; Figueroa-Feliciano, E.; Fleming, B.; Friedland, A.; Fujikawa, B.K.; Gaisser, T.K.; Galeazzi, M.; Galehouse, D.C.; Galindo-Uribarri, A.; Garvey, G.T.; Gautam, S.; Gilje, K.E.; Gonzalez-Garcia, M.; Goodman, M.C.; Gordon, H.; Gramellini, E.; Green, M.P.; Guglielmi, A.; Hackenburg, R.W.; Hackenburg, A.; Halzen, F.; Han, K.; Hans, S.; Harris, D.; Heeger, K.M.; Herman, M.; Hill, R.; Holin, A.; Huber, P.; Jaffe, D.E.; Johnson, R.A.; Joshi, J.; Karagiorgi, G.; Kaufman, L.J.; Kayser, B.; Kettell, S.H.; Kirby, B.J.; Klein, J.R.; Kolomensky, Yu. G.; Kriske, R.M.; Lane, C.E.; Langford, T.J.; Lankford, A.; Lau, K.; Learned, J.G.; Ling, J.; Link, J.M.; Lissauer, D.; Littenberg, L.; Littlejohn, B.R.; Lockwitz, S.; Lokajicek, M.; Louis, W.C.; Luk, K.; Lykken, J.; Marciano, W.J.; Maricic, J.; Markoff, D.M.; Martinez Caicedo, D.A.; Mauger, C.; Mavrokoridis, K.; McCluskey, E.; McKeen, D.; McKeown, R.; Mills, G.; Mocioiu, I.; Monreal, B.; Mooney, M.R.; Morfin, J.G.; Mumm, P.; Napolitano, J.; Neilson, R.; Nelson, J.K.; Nessi, M.; Norcini, D.; Nova, F.; Nygren, D.R.; Orebi Gann, G.D.; Palamara, O.; Parsa, Z.; Patterson, R.; Paul, P.; Pocar, A.; Qian, X.; Raaf, J.L.; Rameika, R.; Ranucci, G.; Ray, H.; Reyna, D.; Rich, G.C.; Rodrigues, P.; Romero, E.Romero; Rosero, R.; Rountree, S.D.; Rybolt, B.; Sanchez, M.C.; Santucci, G.; Schmitz, D.; Scholberg, K.; Seckel, D.; Shaevitz, M.; Shrock, R.; Smy, M.B.; Soderberg, M.; Sonzogni, A.; Sousa, A.B.; Spitz, J.; St. John, J.M.; Stewart, J.; Strait, J.B.; Sullivan, G.; Svoboda, R.; Szelc, A.M.; Tayloe, R.; Thomson, M.A.; Toups, M.; Vacheret, A.; Vagins, M.; Van de Water, R.G.; Vogelaar, R.B.; Weber, M.; Weng, W.; Wetstein, M.; White, C.; White, B.R.; Whitehead, L.; Whittington, D.W.; Wilking, M.J.; Wilson, R.J.; Wilson, P.; Winklehner, D.; Winn, D.R.; Worcester, E.; Yang, L.; Yeh, M.; Yokley, Z.W.; Yoo, J.; Yu, B.; Yu, J.; Zhang, C.

    2015-01-01

    The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program (WINP) at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summ...

  8. The Intermediate Neutrino Program

    Energy Technology Data Exchange (ETDEWEB)

    Adams, C. [Yale Univ., New Haven, CT (United States); Alonso, J. R. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Ankowski, A. M. [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Asaadi, J. A. [Syracuse Univ., NY (United States); Ashenfelter, J. [Yale Univ., New Haven, CT (United States); Axani, S. N. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Babu, K [Oklahoma State Univ., Stillwater, OK (United States); Backhouse, C. [California Inst. of Technology (CalTech), Pasadena, CA (United States); Band, H. R. [Yale Univ., New Haven, CT (United States); Barbeau, P. S. [Duke Univ., Durham, NC (United States); Barros, N. [Univ. of Pennsylvania, Philadelphia, PA (United States); Bernstein, A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Betancourt, M. [Illinois Inst. of Technology, Chicago, IL (United States); Bishai, M. [Brookhaven National Lab. (BNL), Upton, NY (United States); Blucher, E. [Univ. of Chicago, IL (United States); Bouffard, J. [State Univ. of New York (SUNY), Albany, NY (United States); Bowden, N. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Brice, S. [Illinois Inst. of Technology, Chicago, IL (United States); Bryan, C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Camilleri, L. [Columbia Univ., New York, NY (United States); Cao, J. [Inst. of High Energy Physics, Beijing (China); Carlson, J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Carr, R. E. [Columbia Univ., New York, NY (United States); Chatterjee, A. [Univ. of Texas, Arlington, TX (United States); Chen, M. [Univ. of California, Irvine, CA (United States); Chen, S. [Tsinghua Univ., Beijing (China); Chiu, M. [Brookhaven National Lab. (BNL), Upton, NY (United States); Church, E. D. [Illinois Inst. of Technology, Chicago, IL (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Collar, J. I. [Univ. of Chicago, IL (United States); Collin, G. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Conrad, J. M. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Convery, M. R. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Cooper, R. L. [Indiana Univ., Bloomington, IN (United States); Cowen, D. [Pennsylvania State Univ., University Park, PA (United States); Davoudiasl, H. [Brookhaven National Lab. (BNL), Upton, NY (United States); Gouvea, A. D. [Northwestern Univ., Evanston, IL (United States); Dean, D. J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Deichert, G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Descamps, F. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); DeYoung, T. [Michigan State Univ., East Lansing, MI (United States); Diwan, M. V. [Brookhaven National Lab. (BNL), Upton, NY (United States); Djurcic, Z. [Argonne National Lab. (ANL), Argonne, IL (United States); Dolinski, M. J. [Drexel Univ., Philadelphia, PA (United States); Dolph, J. [Brookhaven National Lab. (BNL), Upton, NY (United States); Donnelly, B. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Dwyer, D. A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Dytman, S. [Univ. of Pittsburgh, PA (United States); Efremenko, Y. [Univ. of Tennessee, Knoxville, TN (United States); Everett, L. L. [Univ. of Wisconsin, Madison, WI (United States); Fava, A. [University of Padua, Padova (Italy); Figueroa-Feliciano, E. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Fleming, B. [Yale Univ., New Haven, CT (United States); Friedland, A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Fujikawa, B. K. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gaisser, T. K. [Univ. of Delaware, Newark, DE (United States); Galeazzi, M. [Univ. of Miami, FL (United States); Galehouse, DC [Univ. of Akron, OH (United States); Galindo-Uribarri, A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Garvey, G. T. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gautam, S. [Tribhuvan Univ., Kirtipur (Nepal); Gilje, K. E. [Illinois Inst. of Technology, Chicago, IL (United States); Gonzalez-Garcia, M. [Stony Brook Univ., NY (United States); Goodman, M. C. [Argonne National Lab. (ANL), Argonne, IL (United States); Gordon, H. [Brookhaven National Lab. (BNL), Upton, NY (United States); Gramellini, E. [Yale Univ., New Haven, CT (United States); Green, M. P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Guglielmi, A. [University of Padua, Padova (Italy); Hackenburg, R. W. [Brookhaven National Lab. (BNL), Upton, NY (United States); Hackenburg, A. [Yale Univ., New Haven, CT (United States); Halzen, F. [Univ. of Wisconsin, Madison, WI (United States); Han, K. [Yale Univ., New Haven, CT (United States); Hans, S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Harris, D. [Illinois Inst. of Technology, Chicago, IL (United States); Heeger, K. M. [Yale Univ., New Haven, CT (United States); Herman, M. [Brookhaven National Lab. (BNL), Upton, NY (United States); Hill, R. [Univ. of Chicago, IL (United States); Holin, A. [Univ. College London, Bloomsbury (United Kingdom); Huber, P. [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Jaffe, D. E. [Brookhaven National Lab. (BNL), Upton, NY (United States); Johnson, R. A. [Univ. of Cincinnati, OH (United States); Joshi, J. [Brookhaven National Lab. (BNL), Upton, NY (United States); Karagiorgi, G. [Univ. of Manchester (United Kingdom); Kaufman, L. J. [Indiana Univ., Bloomington, IN (United States); Kayser, B. [Illinois Inst. of Technology, Chicago, IL (United States); Kettell, S. H. [Brookhaven National Lab. (BNL), Upton, NY (United States); Kirby, B. J. [Brookhaven National Lab. (BNL), Upton, NY (United States); Klein, J. R. [Univ. of Texas, Arlington, TX (United States); Kolomensky, Y. G. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States); Kriske, R. M. [Univ. of Minnesota, Minneapolis, MN (United States); Lane, C. E. [Drexel Univ., Philadelphia, PA (United States); Langford, T. J. [Yale Univ., New Haven, CT (United States); Lankford, A. [Univ. of California, Irvine, CA (United States); Lau, K. [Univ. of Houston, TX (United States); Learned, J. G. [Univ. of Hawaii, Honolulu, HI (United States); Ling, J. [Univ. of Illinois, Urbana-Champaign, IL (United States); Link, J. M. [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Lissauer, D. [Brookhaven National Lab. (BNL), Upton, NY (United States); Littenberg, L. [Brookhaven National Lab. (BNL), Upton, NY (United States); Littlejohn, B. R. [Illinois Inst. of Technology, Chicago, IL (United States); Lockwitz, S. [Illinois Inst. of Technology, Chicago, IL (United States); Lokajicek, M. [Inst. of Physics of the Academy of Sciences of Czech Republic, Prague (Czech Republic); Louis, W. C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Luk, K. [Univ. of California, Berkeley, CA (United States); Lykken, J. [Illinois Inst. of Technology, Chicago, IL (United States); Marciano, W. J. [Brookhaven National Lab. (BNL), Upton, NY (United States); Maricic, J. [Univ. of Hawaii, Honolulu, HI (United States); Markoff, D. M. [North Carolina Central Univ., Durham, NC (United States); Caicedo, D. A. M. [Illinois Inst. of Technology, Chicago, IL (United States); Mauger, C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mavrokoridis, K. [Univ. of Liverpool (United Kingdom); McCluskey, E. [Illinois Inst. of Technology, Chicago, IL (United States); McKeen, D. [Univ. of Washington, Seattle, WA (United States); McKeown, R. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Mills, G. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mocioiu, I. [Pennsylvania State Univ., University Park, PA (United States); Monreal, B. [Univ. of California, Santa Barbara, CA (United States); Mooney, M. R. [Brookhaven National Lab. (BNL), Upton, NY (United States); Morfin, J. G. [Illinois Inst. of Technology, Chicago, IL (United States); Mumm, P. [National Inst. of Standards and Technology (NIST), Boulder, CO (United States); Napolitano, J. [Temple Univ., Philadelphia, PA (United States); Neilson, R. [Drexel Univ., Philadelphia, PA (United States); Nelson, J. K. [College of William and Mary, Williamsburg, VA (United States); Nessi, M. [European Organization for Nuclear Research (CERN), Geneva (Switzerland); Norcini, D. [Yale Univ., New Haven, CT (United States); Nova, F. [Univ. of Texas, Austin, TX (United States); Nygren, D. R. [Univ. of Texas, Arlington, TX (United States); Gann, GDO [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States); Palamara, O. [Illinois Inst. of Technology, Chicago, IL (United States); Parsa, Z. [Brookhaven National Lab. (BNL), Upton, NY (United States); Patterson, R. [California Inst. of Technology (CalTech), Pasadena, CA (United States); Paul, P. [Stony Brook Univ., NY (United States); Pocar, A. [Univ. of Massachusetts, Amherst, MA (United States); Qian, X. [Brookhaven National Lab. (BNL), Upton, NY (United States); Raaf, J. L. [Illinois Inst. of Technology, Chicago, IL (United States); Rameika, R. [Illinois Inst. of Technology, Chicago, IL (United States); Ranucci, G. [National Inst. of Nuclear Physics, Milano (Italy); Ray, H. [Univ. of Florida, Gainesville, FL (United States); Reyna, D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rich, G. C. [Triangle Universities Nuclear Lab., Durham, NC (United States); Rodrigues, P. [Univ. of Rochester, NY (United States); Romero, E. R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States); Rosero, R. [Brookhaven National Lab. (BNL), Upton, NY (United States); Rountree, S. D. [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Rybolt, B. [Univ. of Tennessee, Knoxville, TN (United States); Sanchez, M. C. [Iowa State Univ., Ames, IA (United States); Santucci, G. [Stony Brook Univ., NY (United States); Schmitz, D. [Univ. of Chicago, IL (United States); Scholberg, K. [Duke Univ., Durham, NC (United States); Seckel, D. [Univ. of Delaware, Newark, DE (United States); Shaevitz, M. [Columbia Univ., New York, NY (United States); Shrock, R. [Stony Brook Univ., NY (United States); Smy, M. B. [Univ. of California, Irvine, CA (United States); Soderberg, M. [Syracuse Univ., NY (United States); Sonzogni, A. [Brookhaven National Lab. (BNL), Upton, NY (United States); Sousa, A. B. [Univ. of Cincinnati, OH (United States); Spitz, J. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); John, J. M. S. [Univ. of Cincinnati, OH (United States); Stewart, J. [Brookhaven National Lab. (BNL), Upton, NY (United States); Strait, J. B. [Illinois Inst. of Technology, Chicago, IL (United States); Sullivan, G. [Univ. of Maryland, College Park, MD (United States); Svoboda, R. [Univ. of California, Davis, CA (United States); Szelc, A. M. [Yale Univ., New Haven, CT (United States); Tayloe, R. [Indiana Univ., Bloomington, IN (United States); Thomson, M. A. [Univ. of Cambridge (United Kingdom); Toups, M. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Vacheret, A. [Univ. of Oxford (United Kingdom); Vagins, M. [Univ. of California, Irvine, CA (United States); Water, R. G. V. D. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Vogelaar, R. B. [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Weber, M. [Bern (Switzerland); Weng, W. [Brookhaven National Lab. (BNL), Upton, NY (United States); Wetstein, M. [Univ. of Chicago, IL (United States); White, C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); White, B. R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Whitehead, L. [Univ. of Houston, TX (United States); Whittington, D. W. [Indiana Univ., Bloomington, IN (United States); Wilking, M. J. [Stony Brook Univ., NY (United States); Wilson, R. J. [Colorado State Univ., Fort Collins, CO (United States); Wilson, P. [Illinois Inst. of Technology, Chicago, IL (United States); Winklehner, D. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Winn, D. R. [Fairfield Univ., CT (United States); Worcester, E. [Brookhaven National Lab. (BNL), Upton, NY (United States); Yang, L. [Univ. of Illinois, Urbana-Champaign, IL (United States); Yeh, M [Brookhaven National Lab. (BNL), Upton, NY (United States); Yokley, Z. W. [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Yoo, J. [Illinois Inst. of Technology, Chicago, IL (United States); Yu, B. [Brookhaven National Lab. (BNL), Upton, NY (United States); Yu, J. [Univ. of Texas, Arlington, TX (United States); Zhang, C. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2017-04-03

    The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program (WINP) at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop.

  9. 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 Dan...... had a 31% (95% CI: 17; 49) reduced risk of severe hypoglycemia compared to patients on fewer daily injections (p = 0.015). CONCLUSIONS: Despite improvements in metabolic control over a decade the prevalence of severe hypoglycemic events remained unchanged. More intensive treatments such as insulin......DiabKids, a national diabetes register for children and adolescents. The register contains data on patients with type 1 diabetes with an ascertainment rate of 99%. Data from 3320 patients aged 0-18 yr was included in the study period from 1998 to 2009 and analyzed using a negative binomial model. RESULTS: One thousand...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...... 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.......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...

  11. Optimizing glycemic control and minimizing the risk of hypoglycemia in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Stanley S Schwartz

    2013-05-01

    Full Text Available Diabetic microvascular and macrovascular complications arise from hyperglycemia, presenting an increasing healthcare burden as the diabetic population continues to grow. Clinical trial evidence indicates that antihyperglycemic medications are beneficial with regard to microvascular disease (retinopathy, renal impairment, and perhaps neuropathy; however, the benefit of aggressive use of these medications with regard to cardiovascular risk has been less clear in recent studies. These studies were confounded by the propensity of the antihyperglycemic medications involved to cause hypoglycemia, which itself presents cardiovascular risk. This article presents additional context for these seemingly discordant results and maintains that the achievement of glycemic targets is warranted in most patients and provides cardiovascular benefit, provided that hypoglycemia is avoided and the treatment regimen is tailored to the needs of the individual patient. A treatment approach that is driven by these principles and emphasizes diet and exercise, a combination of noninsulin antidiabetic agents, not including sulfonylureas and glinides, and judicious use of insulin is also presented.

  12. Hypoketonemia and age-related fasting hypoglycemia in growth hormone deficiency.

    Science.gov (United States)

    Wolfsdorf, J I; Sadeghi-Nejad, A; Senior, B

    1983-05-01

    Body fuels were measured in 45 normal children and 17 growth hormone-deficient patients after 24 hours of fasting. After three months of therapy with human Growth Hormone (hGH) 16 of the patients were restudied. In all groups, beta-hydroxybutyrate (BOHB) concentrations correlated inversely with age and with glucose concentrations. When adjusted for these factors, the concentrations of BOHB were significantly lower in the growth hormone-deficient patients than in the control children, before (P less than 0.01) as well as after therapy (P less than 0.01). Only the five youngest patients became hypoglycemic. During fasting, ketones, which serve as an alternative fuel for the brain, spare glucose. Thus, a shortage of ketones would compromise the ability of the patient to conserve glucose and predispose the patient to fasting hypoglycemia. Accordingly, we propose that hypoketonemia is a critical factor in the genesis of fasting hypoglycemia in growth hormone deficiency.

  13. 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.

  14. Major Increases between Pre- and Post-breakfast Glucose Levels May Predict Nocturnal Hypoglycemia in Type 2 Diabetes.

    Science.gov (United States)

    Takeishi, Soichi; Mori, Akihiro; Kawai, Miyuka; Yoshida, Yohei; Hachiya, Hiroki; Yumura, Takayuki; Ito, Shun; Shibuya, Takashi; Fushimi, Nobutoshi; Ohashi, Noritsugu; Kawai, Hiromi

    Objective The aim of this study was to determine whether nocturnal hypoglycemia may be predicted according to morning glucose levels. Methods We retrospectively evaluated 106 patients with type 2 diabetes who underwent continuous glucose monitoring during admission. The pre-breakfast glucose level (Pre-breakfast level), highest postprandial glucose level within 3 hours after breakfast (Highest level), time from the start of breakfast to the highest postprandial glucose level (Highest time), difference between the pre-breakfast and highest postprandial breakfast glucose levels (Increase), area under the glucose curve (≥180 mg/dL) within 3 hours after breakfast (Morning AUC), post-breakfast glucose gradient (Gradient), and the increase-to-pre-breakfast ratio (Increase/Pre-breakfast) were calculated. The subjects were divided into hypoglycemic and non-hypoglycemic patients and compared for the above parameters using the t-test. A receiver operating characteristic analysis was used to determine the optimal cut-off values to predict nocturnal hypoglycemia (Hypoglycemia). Results Twenty-eight patients (26.4%) had hypoglycemia. The Pre-breakfast levels were significantly lower in patients with hypoglycemia than those without (p=0.03). The Increases were significantly higher in patients with hypoglycemia than those without (p=0.047). The Increase/Pre-breakfast ratio were significantly larger in patients with hypoglycemia than those without (p=0.0002). Their cut-off values were as follows (level, sensitivity, specificity, and area under the curve): 123 mg/dL, 0.89, 0.55, and 0.78 (pbreakfast glucose levels may predict nocturnal hypoglycemia in patients with type 2 diabetes.

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

    DEFF Research Database (Denmark)

    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....

  16. Intermediate energy data

    International Nuclear Information System (INIS)

    Koning, A.J.; Fukahori, T.; Hasegawa, A.

    1998-01-01

    Subgroup 13 (SG13) on Intermediate Energy Nuclear data was formed by NEA Nuclear Science Committee to solve common problems of these types of data for nuclear applications. An overview is presented in this final report of the present activities of SG13, including data needs, high-priority nuclear data request list (nuclides), compilation of experimental data, specialists meetings and benchmarks, data formats and data libraries. Some important accomplishments are summarized, and recommendations are presented. (R.P.)

  17. Factors Affecting the Ability of People With Diabetes to Avoid Hypoglycemia.

    Science.gov (United States)

    Wu, Fei-Ling; Wu, En-Chang; Chang, Yue-Cune; Hu, Wen-Yu; Juang, Jyuhn-Huarng; Yeh, Mei Chang

    2018-02-01

    Hypoglycemia is recognized as a limiting factor in diabetes management. Fear of experiencing hypoglycemia may lead to lower quality of life, impaired glycemic control, and emotional distress, all of which impair the ability of patients to self-manage their diabetes effectively. Problem solving is central to diabetes self-management and may help patients achieve effective self-care of their disease. The aim of this study was to investigate the ability of people with diabetes to avoid hypoglycemia and to explore associated factors. A cross-sectional, descriptive design was used for the study. Data were collected using a demographic and disease characteristics datasheet, the Hypoglycemic Problem Solving Scale, and the Disease-Associated Negative Mood Scale. Three hundred thirteen participants were recruited, with a mean age of 55.49 years. The average item score for the questions on hypoglycemic problem-solving ability was 2.43 (SD = 0.75). In comparing Hypoglycemic Problem Solving Scale subscales, participants scored highest on the problem orientation subscales and lowest on the problem-solving skills subscales. Multiple regression analysis revealed that being younger and unmarried and having a higher level of education, a diagnosis of Type 1 diabetes, and a lower negative mood score were each significantly associated with greater problem-solving ability as regards hypoglycemic events. We suggest that patients with diabetes, especially those who are older or with lower levels of education, receive disease-related psychological interventions and that healthcare professionals teach problem-solving abilities in conjunction with hypoglycemia management.

  18. Endocrine and metabolic emergencies in children: hypocalcemia, hypoglycemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis

    OpenAIRE

    Se Young Kim

    2015-01-01

    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 shoul...

  19. Hypoglycemia Prevention and User Acceptance of an Insulin Pump System with Predictive Low Glucose Management.

    Science.gov (United States)

    Choudhary, Pratik; Olsen, Birthe S; Conget, Ignacio; Welsh, John B; Vorrink, Linda; Shin, John J

    2016-05-01

    The MiniMed 640G sensor-augmented insulin pump system (Medtronic, Inc., Northridge, CA) can automatically suspend insulin delivery in advance of predicted hypoglycemia and restart it upon recovery. The aims of this analysis were to determine the rate at which predicted hypoglycemia was avoided with this strategy, as well as to assess user acceptance of the system and its insulin management features. Forty subjects with type 1 diabetes used the system for 4 weeks. We retrospectively evaluated performance of the system, using downloaded pump and sensor data, and evaluated user acceptance via questionnaires. There were 2,322 suspend before low events (2.1 per subject-day). The mean (± SD) duration of pump suspension events was 56.4 ± 9.6 min, and the mean subsequent sensor glucose (SG) nadir was 71.8 ± 5.2 mg/dL. SG values following 1,930 (83.1%) of the predictive suspensions did not reach the preset low limit. Nadir SG values of ≤50 and ≤60 mg/dL were seen in 207 (8.9%) and 356 (15.3%) of the predictive suspensions, respectively. Blood glucose (BG) and SG values before and during the study were comparable (P > 0.05). The mean absolute relative difference between paired SG and BG values was 10.9 ± 13.8%. Subjects felt confident using the system, agreed that it helped protect them from hypoglycemia, and wished to continue using it. Automatic insulin pump suspension as implemented in the MiniMed 640G system can help patients avoid hypoglycemia, without significantly increasing hyperglycemia.

  20. Trends in Antihyperglycemic Medication Prescriptions and Hypoglycemia in Older Adults: 2002-2013.

    Directory of Open Access Journals (Sweden)

    Kristin K Clemens

    Full Text Available Over the last decade, several new antihyperglycemic medications have been introduced including those associated with a lower hypoglycemia risk. We aimed to investigate how these medications are being prescribed to older adults in our region.We conducted population-based cross-sectional analyses of older adults (mean age 75 years with treated diabetes in Ontario, Canada from 2002 until 2013, to examine the percentage prescribed insulin, sulphonylureas, alpha-glucosidase inhibitors, metformin, thiazolidinediones, meglitinides, and dipeptidyl peptidase-4 inhibitors. Over the study period, we also examined their hospital encounters for hypoglycemia (emergency room or inpatient encounter.The mean age of treated patients increased slightly over the study quarters and the proportion that were women declined. With the exception of chronic kidney disease, cancer, dementia, and neuropathy, the percentage with a comorbidity appeared to decline. The percentage of treated patients prescribed metformin, gliclazide and dipeptidyl peptidase-4 inhibitors increased as did combination therapy. Glyburide and thiazolidinedione prescriptions declined, and insulin use remained stable. In those with newly treated diabetes, the majority were prescribed metformin, with smaller percentages prescribed insulin and other oral agents. Although the absolute number of treated patients with a hypoglycemia encounter increased until mid-2006 and then decreased, the overall percentage with an encounter declined over the study period (0.8% with an event in the first quarter, 0.4% with an event in the last quarter.Antihyperglycemic medications with safer profiles are being increasingly prescribed to older adults. In this setting there has been a decrease in the percentage of treated patients with a hospital encounter for hypoglycemia.

  1. Long-Term Prediction of Severe Hypoglycemia in Type 1 Diabetes

    DEFF Research Database (Denmark)

    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....

  2. Ocular Myasthenia Gravis, Hashimoto’s Thyroiditis, Iron Deficiency Anemia, and Reactive Hypoglycemia

    Directory of Open Access Journals (Sweden)

    Füsun Mayda Domaç

    2009-06-01

    Full Text Available Myasthenia gravis (MG may occur in association with other organ- specific or nonspecific autoimmune diseases. In our study, we present a patient with ocular myasthenia, Hashimoto’s thyroiditis, and iron deficiency anemia who later developed reactive hypoglycemia. A 25-year-old woman with complaints of fluctuating extraocular muscle weakness, ptosis, and diplopia was examined. MG, type I (ocular MG, was confirmed by an elevated titer of anti-acetylcholine receptor antibodies in serum (7 nmol/l, normal <0.6 and positive edrophonium test. Nerve conduction studies, needle electromyography, repetitive stimulation tests, and mediasten MRI were normal. The coexistence of Hashimoto's thyroiditis was diagnosed by the presence of a diffuse thyroid enlargement, elevated titers of anti-thyroglobulin antibodies (211.8 IU/ml, normal 0-115, thyroid peroxidase antibodies (356.4 IU/ml, normal 0-34, thyroid stimulating hormone (8.21 uIU/ml, normal 0.27-4.2, and a decreased titer of free-T4 (1.03ng/dl normal 1.8-4.6. Diplopia and ptosis have regressed with 180 mg/day pyridostigmine bromide. On her follow-up period, 8 months later, reactive hypoglycemia has been diagnosed. The coexistence of myastenia gravis, Hashimoto’s thyroiditis and reactive hypoglycemia was not found in the literature. We should take into consideration the association and the importance of recognizing and treating these pathologies in myastenia gravis. Turk Jem 2009; 13: 31-3

  3. Potential link between post-acute ischemic stroke exposure to hypoglycemia and hemorrhagic transformation.

    Science.gov (United States)

    Klingbeil, Kyle D; Koch, Sebastian; Dave, Kunjan R

    2017-01-01

    Hemorrhagic transformation is a severe complication of acute ischemic stroke owing to its limited treatment options and poor prognosis. In the last decade, the rates of hemorrhagic transformation incidence have been associated with blood glucose levels. In particular, hyperglycemia at the time of admission has been associated with increased rates of hemorrhagic transformation in acute ischemic stroke patients. Recent pilot clinical trials have attempted to use intensive insulin therapy during stroke treatment to reduce the severity of cerebral infarction and possibly alleviate the risk of hemorrhagic transformation. However, the results of these studies have shown no clear clinical benefit. In addition, intensive insulin therapy has increased rates of hypoglycemia which may be associated with larger infarct growth. We hypothesize that hypoglycemia, similarly to hyperglycemia, is a risk factor for worse outcomes in acute ischemic stroke by promoting hemorrhagic transformation. This review serves to call attention to patterns present within intensive insulin therapy trials and shed light into the pathophysiological effects of hypoglycemia. It is critical that efforts be directed toward the prevention of hemorrhagic transformation by optimizing insulin therapy during the treatment of acute ischemic stroke.

  4. Incidence and risk factors of hypoglycemia among Type 2 diabetic patients in a South Indian hospital.

    Science.gov (United States)

    Vikas Pv; Chandrakumar, Abin; Dilip, C; Suriyaprakash, T N K; Thomas, Levin; Surendran, Reshma

    2016-01-01

    The study was aimed at assessing the cumulative incidence of hypoglycemia and precipitating risk factors among type 2 diabetes mellitus in-patients of a tertiary care hospital in South India. The prospective cross sectional study spanning 14 months was conducted in a tertiary care hospital in Kerala. All T2DM patients who were administered any form of insulin during the length of hospital stay was monitored for assessing the hypoglycemic episodes. Any patient with a GRBS value less than 70mg/dL was defined to be hypoglycemic as per the ADA guidelines. The statistical analysis of collected data was performed using SPSS 18 for windows version. Of the 1650 subjects enrolled in the study, 204 subjects developed hypoglycemia. The sample composed of 60.8% females and 39.2% males and the difference was significant with p=0.02. A significant positive correlation was observed between HbA1c values and GRBS value, with a 2 tailed Pearson correlation coefficient of 0.027. On stratifying as per the modality of insulin dose prescribed, 72.5% of the hypoglycemic patients were found to have been administered fixed dose insulin. The cumulative incidence of institutional hypoglycemia among type 2 diabetic inpatients was gauged as 12.36%; among which, 26.96% had asymptomatic episodes. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  5. 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

  6. 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 <3.5 mmol/L during the day (7:00–23:00 and nighttime (23:00–7:00 were selected for further study. In these patients length of QTc and RR intervals, HRV parameters and arrhythmic events were analyzed and collated with CGM data.Results. We observed 39 episodes of nocturnal hypoglycaemia in 32 patients (21.3% and 89 episodes of daytime hypoglycaemia in 46 patients (30.7%. Marked prolongation of QTc (hypo- vs. normoglycemia, respectively: 431 vs. 420 ms; p<0.05 and reduced HRV (hypo- vs. normoglycemia, respectively: SDNN 68 and 90 ms; RMSSD 56 and 61 ms; p <0.05 occurred during episodes of nocturnal hypoglycemia. The same pattern was observed during the day (hypo- vs. normoglycemia, respectively: SDNN 58 and 63 ms; RMSSD 32 and 36 ms; p<0.05. Eleven subjects with nocturnal hypoglycemia demonstrated either ventricular or supraventricular premature complexes. Thirty of subjects with diurnal hypoglycemia also had either ventricular or supraventricular premature complexes. Hypoglycemic episodes vs. normoglycemia were characterized by an increase in ventricular and supraventricular ectopic beats, ST segment and T-wave amplitude depression. Various rhythm abnormalities were associated with cardiovascular autonomic and peripheral neuropathy

  7. 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

  8. Putative identification of components in Zengye Decoction and their effects on glucose consumption and lipogenesis in insulin-induced insulin-resistant HepG2 cells.

    Science.gov (United States)

    Liu, Zhenzhen; Kuang, Wenhua; Xu, Xi; Li, Dandan; Zhu, Wufu; Lan, Zhou; Zhang, Xu

    2018-01-15

    Zengye Decoction (ZYD) is a well-known traditional medicine in China used for treating diseases associated with "Yin deficiency" such as diabetes. However, little information is available on its components, pharmacological effects and underlying mechanisms. This study was designed to identify its active components and evaluate the effects and mechanisms of ZYD on glucose consumption and lipogenesis in insulin-induced insulin-resistant (IR)-HepG2 cells. In this study, 45 compounds of ZYD were putatively identified, in which the iridoid glycosides such as catalpol, aucubin and harpagide were identified as the main components. The insulin-resistant (IR)-HepG2 cell model was established and the effect of ZYD at three doses (0.17, 0.5 and 1.5 μg/mL) on cell growth was evaluated with an IncuCyte™ live-cell imaging system. The effects of ZYD on glucose consumption and uptake were evaluated by glucose consumption and uptake assay. Meanwhile, the effect of ZYD on lipogenesis was investigated in IR-HepG2 cells by oil red O (ORO) staining. Western blot was applied to observe the changes in some of the key factors involved in glucose metabolism and lipogenesis. It was found that the ZYD at a dose of 1.5 μg/mL exhibited an inhibitory activity on IR-HepG2 cell growth. Besides, ZYD at doses of 0.5 and 1.5 μg/mL accelerated the glucose consumption, glucose uptake and reduced the lipogenesis in the IR-HepG2 cells. Western blot studies revealed that ZYD phosphorylated AMP-activated protein kinase α subunits (AMPKα), upregulated hexokinase (HK), phosphorylated acetyl-CoA carboxylase alpha (pACC1) and carnitine palmitoyltransferase 1A (CPT1A) in the IR-HepG2 cells. These results indicate ZYD promotes glucose consumption and uptake, and attenuates lipogenesis in IR-HepG2 cells, which may be involved in activating AMPK and regulating its downstream factors including HK, pACC1 and CPT1A. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Insulin induces a transcriptional activation of epiregulin, HB-EGF and amphiregulin, by a PI3K-dependent mechanism: Identification of a specific insulin-responsive promoter element

    International Nuclear Information System (INIS)

    Ornskov, Dorthe; Nexo, Ebba; Sorensen, Boe S.

    2007-01-01

    Previously we have shown that insulin-stimulation of RT4 bladder cancer cells leads to increased proliferation, which require HER1 activation, and is accompanied by increased mRNA expression of the EGF-ligands heparin-binding EGF-like growth factor (HB-EGF), amphiregulin (AR), and epiregulin (EPI) [D. Ornskov, E. Nexo, B.S. Sorensen, Insulin-induced proliferation of bladder cancer cells is mediated through activation of the epidermal growth factor system, FEBS J. 273 (2006) 5479-5489]. In the present paper, we have investigated the molecular mechanism leading to this insulin-induced expression. We monitored the decay of mRNA after inhibiting transcription with Actinomycin D and demonstrated that the insulin-mediated increase was not caused by enhanced mRNA stability. In untreated cells, HB-EGF mRNA was the least stable, whereas AR and EPI mRNA decayed with slower kinetics. However, promoter analysis of HB-EGF and EPI demonstrated that insulin stimulated transcription. Studies on the EPI promoter identified the insulin-responsive element to be located in the region -564 to -365 bp. This region contains potential binding sites for the transcription factors SP1, AP1, and NF-κB. Interestingly, all three transcription factors can be activated by PI3K. We demonstrate that the insulin-induced expression of HB-EGF, AR, and EPI mRNA is completely prevented by the specific PI3K inhibitor Wortmannin, suggesting an involvement of the PI3K

  10. Bacterial intermediate filaments

    DEFF Research Database (Denmark)

    Charbon, Godefroid; Cabeen, M.; Jacobs-Wagner, C.

    2009-01-01

    Crescentin, which is the founding member of a rapidly growing family of bacterial cytoskeletal proteins, was previously proposed to resemble eukaryotic intermediate filament (IF) proteins based on structural prediction and in vitro polymerization properties. Here, we demonstrate that crescentin...... also shares in vivo properties of assembly and dynamics with IF proteins by forming stable filamentous structures that continuously incorporate subunits along their length and that grow in a nonpolar fashion. De novo assembly of crescentin is biphasic and involves a cell size-dependent mechanism...... a new function for MreB and providing a parallel to the role of actin in IF assembly and organization in metazoan cells. Additionally, analysis of an MreB localization mutant suggests that cell wall insertion during cell elongation normally occurs along two helices of opposite handedness, each...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  13. 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.

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Role of glucagon in countering hypoglycemia induced by insulin infusion in dogs.

    Science.gov (United States)

    Dobbins, R L; Connolly, C C; Neal, D W; Palladino, L J; Parlow, A F; Cherrington, A D

    1991-12-01

    The aim of the present study was to characterize the role of glucagon in countering the prolonged hypoglycemia resulting from insulin infusion and to determine whether its effect is manifest through glycogenolysis and/or gluconeogenesis. Two groups of 18-h fasted somatostatin-treated dogs were given intraportal insulin at 5 mU.kg-1.min-1. In one group (SimGGN; n = 6), glucagon was infused intraportally so as to mimic the normal response to hypoglycemia. In a second group (BasGGN; n = 6), glucagon was infused at a basal rate. Glucose turnover and gluconeogenesis were assessed by combining tracer and hepatic balance techniques. Exogenous glucose was infused as needed to maintain equivalent hypoglycemia at approximately 45 mg/dl in the two groups. Although glucagon concentrations were significantly different, the levels of other counterregulatory hormones were equivalent in both experimental protocols. Endogenous glucose production (EGP) in SimGGN doubled from 2.4 +/- 0.2 to 5.4 +/- 0.8 mg.kg-1.min-1 by 1 h before dropping to 4.5 +/- 0.2 mg.kg-1.min-1 in the 3rd h of insulin infusion. EGP in BasGGN was initially 2.5 +/- 0.1 mg.kg-1.min-1, unchanged by 1 h, and increased to 3.9 +/- 0.2 mg.kg-1.min-1 by the 3rd h of insulin infusion. In the 1st h of insulin infusion, the rise in gluconeogenesis in both groups was equal and represented only a small part of total EGP. By the 3rd h, gluconeogenesis was the major contributor to total EGP, and gluconeogenic efficiency increased significantly more in SimGGN than BasGGN (261 vs. 140%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  20. Threshold-based insulin-pump interruption for reduction of hypoglycemia.

    Science.gov (United States)

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

    2013-07-18

    The threshold-suspend feature of sensor-augmented insulin pumps is designed to minimize the risk of hypoglycemia by interrupting insulin delivery at a preset sensor glucose value. We evaluated sensor-augmented insulin-pump therapy with and without the threshold-suspend feature in patients with nocturnal hypoglycemia. We randomly assigned patients with type 1 diabetes and documented nocturnal hypoglycemia to receive sensor-augmented insulin-pump therapy with or without the threshold-suspend feature for 3 months. The primary safety outcome was the change in the glycated hemoglobin level. The primary efficacy outcome was the area under the curve (AUC) for nocturnal hypoglycemic events. Two-hour threshold-suspend events were analyzed with respect to subsequent sensor glucose values. A total of 247 patients were randomly assigned to receive sensor-augmented insulin-pump therapy with the threshold-suspend feature (threshold-suspend group, 121 patients) or standard sensor-augmented insulin-pump therapy (control group, 126 patients). The changes in glycated hemoglobin values were similar in the two groups. The mean AUC for nocturnal hypoglycemic events was 37.5% lower in the threshold-suspend group than in the control group (980 ± 1200 mg per deciliter [54.4 ± 66.6 mmol per liter] × minutes vs. 1568 ± 1995 mg per deciliter [87.0 ± 110.7 mmol per liter] × minutes, Ppump was stopped for 2 hours, the mean sensor glucose value was 92.6 ± 40.7 mg per deciliter (5.1 ± 2.3 mmol per liter). Four patients (all in the control group) had a severe hypoglycemic event; no patients had diabetic ketoacidosis. This study showed that over a 3-month period the use of sensor-augmented insulin-pump therapy with the threshold-suspend feature reduced nocturnal hypoglycemia, without increasing glycated hemoglobin values. (Funded by Medtronic MiniMed; ASPIRE ClinicalTrials.gov number, NCT01497938.).

  1. Severe hypoglycemia identifies vulnerable patients with type 2 diabetes at risk for premature death and all-site cancer: the Hong Kong diabetes registry.

    Science.gov (United States)

    Kong, Alice P S; Yang, Xilin; Luk, Andrea; Ma, Ronald C W; So, Wing Yee; Ozaki, Risa; Ting, Rose; Cheung, Kitty; Ho, Chung Shun; Chan, Michael H M; Chow, Chun Chung; Chan, Juliana C N

    2014-04-01

    OBJECTIVE We examined the associations of clinical profiles in type 2 diabetic patients who developed severe hypoglycemia and their clinical outcomes, including death and all-site cancer. RESEARCH DESIGN AND METHODS A consecutive cohort of 8,767 type 2 diabetic patients with and without severe hypoglycemia in the 12 months before enrollment were recruited between 1995 and 2007, with follow-up until 2009. Severe hypoglycemia was defined by ICD-9 codes as hospitalizations resulting from hypoglycemia. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% CIs of clinical factors collected at enrollment for severe hypoglycemia. RESULTS In this cohort, mean age was 57.4 (SD 13.2) years and median disease duration of diabetes was 5 (interquartile range [IQR] 1-11) years. During a median follow-up of 6.71 (IQR 3.47-10.38) years, 235 patients had severe hypoglycemia (incidence 3.96 [95% CI 3.45-4.46] per 1,000 patient-years). At enrollment, patients with and without severe hypoglycemia had similar cancer rates. During follow-up, patients with severe hypoglycemia had a higher incidence of all-site cancer (13.4 vs. 6.4%, P < 0.0001) and mortality (32.8 vs. 11.2%, P < 0.0001) than those without severe hypoglycemia. After adjusting for confounders, old age, low BMI, high glycated hemoglobin, low triglyceride (TG), low LDL cholesterol (LDL-C), albuminuria, and chronic kidney disease were independent predictors for severe hypoglycemia. CONCLUSIONS In type 2 diabetes, severe hypoglycemia is associated with advanced age, renal dysfunction, poor glycemic control, and cancer subphenotypes (low BMI, low LDL-C, and low TG).

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

    Science.gov (United States)

    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.

  3. An international survey on hypoglycemia among insulin-treated type I and type II diabetes patients: Turkey cohort of the non-interventional IO HAT study.

    Science.gov (United States)

    Emral, Rıfat; Tetiker, Tamer; Sahin, Ibrahim; Sari, Ramazan; Kaya, Ahmet; Yetkin, İlhan; Cil, Sefika Uslu; Tütüncü, Neslihan Başcıl

    2018-02-13

    Limited real-world data are currently available on hypoglycemia in diabetes patients. The International Operations Hypoglycemia Assessment Tool (IO HAT) study was designed to estimate hypoglycemia in insulin-treated type I (T1DM) and type II (T2DM) diabetes mellitus patients from 9 countries. The data from Turkey cohort are presented here. A non-interventional study to determine the hypoglycemia incidence, retrospectively and prospectively, in Turkish T1DM and T2DM patients using a 2-part self-assessment questionnaire. Overall, 2348 patients were enrolled in the Turkey cohort (T1DM = 306 patients, T2DM = 2042 patients). In T1DM patients, 96.8% patients reported hypoglycemic events (Incidence rate [IR]: 68.6 events per patient-year [ppy]), prospectively, while 74.0% patients reported hypoglycemic events (IR: 51.7 events ppy), retrospectively. In T2DM patients, 95.9% patients (IR: 28.3 events ppy) reported hypoglycemic events, prospectively, while 53.6% patients (IR: 23.0 events ppy) reported hypoglycemic events, retrospectively. Nearly all patients reported hypoglycemia during the prospective period. This is a first patient-reported dataset on hypoglycemia in Turkish, insulin-treated diabetes patients. A high incidence of patient-reported hypoglycemia confirms that hypoglycemia remains under-estimated. Hypoglycemia increased healthcare utilization impacting patients' quality of life. Hypoglycemia remains a common side effect with insulin-treatment and strategies to optimize therapy and reduce hypoglycemia occurrence in diabetes patients are required. Clinicaltrials.gov, NCT02306681 (Date of registration: 12 Nov 2014; retrospectively registered).

  4. Information acquisition and financial intermediation

    OpenAIRE

    Boyarchenko, Nina

    2012-01-01

    This paper considers the problem of information acquisition in an intermediated market, where the specialists have access to superior technology for acquiring information. These informational advantages of specialists relative to households lead to disagreement between the two groups, changing the shape of the intermediation-constrained region of the economy and increasing the frequency of periods when the intermediation constraint binds. Acquiring the additional information is, however, cost...

  5. Intermediate inputs and economic productivity.

    Science.gov (United States)

    Baptist, Simon; Hepburn, Cameron

    2013-03-13

    Many models of economic growth exclude materials, energy and other intermediate inputs from the production function. Growing environmental pressures and resource prices suggest that this may be increasingly inappropriate. This paper explores the relationship between intermediate input intensity, productivity and national accounts using a panel dataset of manufacturing subsectors in the USA over 47 years. The first contribution is to identify sectoral production functions that incorporate intermediate inputs, while allowing for heterogeneity in both technology and productivity. The second contribution is that the paper finds a negative correlation between intermediate input intensity and total factor productivity (TFP)--sectors that are less intensive in their use of intermediate inputs have higher productivity. This finding is replicated at the firm level. We propose tentative hypotheses to explain this association, but testing and further disaggregation of intermediate inputs is left for further work. Further work could also explore more directly the relationship between material inputs and economic growth--given the high proportion of materials in intermediate inputs, the results in this paper are suggestive of further work on material efficiency. Depending upon the nature of the mechanism linking a reduction in intermediate input intensity to an increase in TFP, the implications could be significant. A third contribution is to suggest that an empirical bias in productivity, as measured in national accounts, may arise due to the exclusion of intermediate inputs. Current conventions of measuring productivity in national accounts may overstate the productivity of resource-intensive sectors relative to other sectors.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Nondiabetic Hypoglycemia

    Science.gov (United States)

    ... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... an Endocrinologist Clinical Trials Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ...

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

    Science.gov (United States)

    Heller, Simon; Damm, Peter; Mersebach, Henriette; Skjøth, Trine Vang; Kaaja, Risto; Hod, Moshe; Durán-García, Santiago; McCance, David; Mathiesen, Elisabeth R

    2010-03-01

    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 (IAsp versus human insulin were 0.9 versus 2.4, 0.9 versus 2.4, 0.3 versus 1.2, and 0.2 versus 2.2 episodes per patient per year, respectively (NS). CONCLUSIONS These data suggest that initiation of insulin analog treatment preconception rather than during early pregnancy may result in a lower risk of severe hypoglycemia in women with type 1 diabetes.

  10. Pediatric patient with hyperketotic hypoglycemia diagnosed with glycogen synthase deficiency due to the novel homozygous mutation in GYS2

    Directory of Open Access Journals (Sweden)

    Edyta Szymańska

    2015-09-01

    A random, asymptomatic hypoglycemia with ketonuria was found in this patient at the age of 7. His developmental parameters were within normal ranges. Oral glucose tolerance test showed normal baseline blood levels of glucose, insulin and lactate, and their increase following glucose intake. Eight-hour fasting plasma glucose test, revealed glucose blood level of 34 mg/dl with no clinical symptoms. The results of these tests suggested GSD 0. Molecular analysis of the GYS2 gene was not feasible, but this particular gene was included in the panel of hypoglycemia of whole exome sequencing (WES which was at our disposal.

  11. Functional Connectivity of Insula, Basal Ganglia, and Prefrontal Executive Control Networks during Hypoglycemia in Type 1 Diabetes.

    Science.gov (United States)

    Bolo, Nicolas R; Musen, Gail; Simonson, Donald C; Nickerson, Lisa D; Flores, Veronica L; Siracusa, Tamar; Hager, Brandon; Lyoo, In Kyoon; Renshaw, Perry F; Jacobson, Alan M

    2015-08-05

    Human brain networks mediating interoceptive, behavioral, and cognitive aspects of glycemic control are not well studied. Using group independent component analysis with dual-regression approach of functional magnetic resonance imaging data, we examined the functional connectivity changes of large-scale resting state networks during sequential euglycemic-hypoglycemic clamp studies in patients with type 1 diabetes and nondiabetic controls and how these changes during hypoglycemia were related to symptoms of hypoglycemia awareness and to concurrent glycosylated hemoglobin (HbA1c) levels. During hypoglycemia, diabetic patients showed increased functional connectivity of the right anterior insula and the prefrontal cortex within the executive control network, which was associated with higher HbA1c. Controls showed decreased functional connectivity of the right anterior insula with the cerebellum/basal ganglia network and of temporal regions within the temporal pole network and increased functional connectivity in the default mode and sensorimotor networks. Functional connectivity reductions in the right basal ganglia were correlated with increases of self-reported hypoglycemic symptoms in controls but not in patients. Resting state networks that showed different group functional connectivity during hypoglycemia may be most sensitive to glycemic environment, and their connectivity patterns may have adapted to repeated glycemic excursions present in type 1 diabetes. Our results suggest that basal ganglia and insula mediation of interoceptive awareness during hypoglycemia is altered in type 1 diabetes. These changes could be neuroplastic adaptations to frequent hypoglycemic experiences. Functional connectivity changes in the insula and prefrontal cognitive networks could also reflect an adaptation to changes in brain metabolic pathways associated with chronic hyperglycemia. The major factor limiting improved glucose control in type 1 diabetes is the significant increase

  12. Welding. Performance Objectives. Intermediate Course.

    Science.gov (United States)

    Vincent, Kenneth

    Several intermediate performance objectives and corresponding criterion measures are listed for each of nine terminal objectives for an intermediate welding course. The materials were developed for a 36-week (3 hours daily) course designed to prepare the student for employment in the field of welding. Electric welding and specialized (TIG & MIG)…

  13. Design and rationale of the IN CONTROL trial: the effects of real-time continuous glucose monitoring on glycemia and quality of life in patients with type 1 diabetes mellitus and impaired awareness of hypoglycemia

    NARCIS (Netherlands)

    van Beers, C.A.J.; Kleijer, S.J.; Serne, E.H.; Geelhoed-Duijvestijn, P.H.; Snoek, F.J.; Kramer, M.H.H.; Diamant, M.

    2015-01-01

    Background: Hypoglycemia is the main side effect of intensified insulin therapy in type 1 diabetes and recognized as a limitation in achieving glycemic targets. Patients with impaired awareness of hypoglycemia have a threefold to sixfold increased risk of severe hypoglycemia. Real-time continuous

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

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik; Dhamrait, Sukhbir S.; Sethi, Amar 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 sim...

  15. Changes in 125I-insulin binding antibodies in diabetic pregnant women on insulin therapy and hypoglycemia in newborns

    International Nuclear Information System (INIS)

    Kohama, Tomoko; Omori, Yasue; Minei, Satomi; Akihisa, Rima; Honda, Masashi; Hirata, Yukimasa

    1982-01-01

    To elucidate whether insulin antibodies in pregnant diabetics are related to changes in insulin requirement during pregnancy, and whether hypoglycemia in newborns of diabetic mothers is influenced by insulin antibodies transferred through the placenta, changes in 125 I-insulin percent binding to insulin antibodies were measured at the first, second and third trimesters of pregnancy and at delivery, in 20 deliveries by 17 diabetics treated with insulin. The free insulin levels in the same serum were also measured for each patient in whom the 125 I-insulin binding was decreased more than 5% in the third trimester. The mean percent of 125 I-insulin binding in the 20 diabetic pregnancies was unchanged in the first (21.2%) and second trimester (21.1%), but tended to decrease to 17.6% in the third trimester and to increase to 24.6% after delivery. The 125 I-insulin percent binding of 5 patients with neonatal hypoglycemia was significantly higher than that of the other patients without hypoglycemia (p 125 I-insulin percent binding was decreased in the third trimester in contrast with an increased insulin dosage. The finding that hypoglycemia tended to occur in the newborns of diabetic mothers with high insulin percent binding to insulin antibody during the third trimester, suggests that maternal insulin antibodies may affect the fetal pancreas. (author)

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

    DEFF Research Database (Denmark)

    Johannesen, Jesper; Svensson, Jannet; Bergholdt, Regine

    2011-01-01

    complications (hypoglycemia and DKA). A BioBank coupled to the Registry comprised serum for measuring S-ACE levels and DNA for ACE genotyping. RESULTS: A total of 1037 individuals were included, aged 9.97 yr (SD 3.84). A total of 622 severe hypoglycemic episodes were observed in 270 individuals. Associations...

  17. A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene

    DEFF Research Database (Denmark)

    Højlund, Kurt; Hansen, Torben; Lajer, Maria

    2004-01-01

    a missense mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene that cosegregated with the disease phenotype (logarithm of odds [LOD] score 3.21). In conclusion, we report a novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia. The findings demonstrate...

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

    Directory of Open Access Journals (Sweden)

    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

  19. 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

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

    Science.gov (United States)

    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

  1. Endocrine and metabolic emergencies in children: hypocalcemia, hypoglycemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis

    Directory of Open Access Journals (Sweden)

    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.

  2. Endocrine and metabolic emergencies in children: hypocalcemia, hypoglycemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis.

    Science.gov (United States)

    Kim, Se Young

    2015-12-01

    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.

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

    Science.gov (United States)

    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.

  4. 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.

  5. Amino acids as substrates in children with growth hormone deficiency and hypoglycemia.

    Science.gov (United States)

    LaFranchi, S; Buist, N R; Jhaveri, B; Klevit, H

    1981-08-01

    In order to investigate the role of amino acid (AA) substrates in the hypoglycemia associated with human growth hormone (hGH) deficiency, we measured 12-hour fasting blood glucose and total quantitative AA concentrations in 11 children with hGH deficiency during three study periods: (1) before hGH replacement; (2) after 12 months of hGH treatment; and (3) after discontinuation of hGH for three months. The results were compared to studies in 16 control subjects. Fasting blood glucose concentrations were significantly (P less than .05) lower in the hGH-deficient children prior to hGH treatment as compared to the control subjects (67.0 +/- 5.3 vs 80.7 +/- 5.3 mg/100 ml, mean +/- SE). Fasting total serum AA concentrations were similar in the patients and in the control subjects; however, after 12 months of hGH replacement, there was a significant (P less than .01) elevation of serum AA (2,750 +/- 170 vs 2,283 micromoles/liter). Fasting serum concentrations of alanine, glycine, arginine, and tryptophan were also significantly elevated (P less than .01) with hGH treatment; ornithine, tyrosine, lysine, methionine, and phenylalanine showed lesser elevations (P less than 0.5), whereas threonine decreased significantly (P less than 0.01). The fasting hypoglycemia seen with isolated hGH deficiency is not an AA substrate-limited disorder. The finding of increased concentrations of AA with hGH replacement suggests increased retention of nitrogen and synthesis of AA for gluconeogenesis due to availability of other substrates.

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

    Science.gov (United States)

    Rhee, Sang Youl; Hong, Soo Min; Chon, Suk; Ahn, Kyu Jeung; Kim, Sung Hoon; Baik, Sei Hyun; Park, Yong Soo; Nam, Moon Suk; Lee, Kwan Woo; Woo, Jeong-Taek; Kim, Young Seol

    2016-01-01

    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.

  7. High incidence of hypoglycemia in stable insulin-treated type 2 diabetes mellitus: continuous glucose monitoring vs. self-monitored blood glucose. Observational prospective study.

    Science.gov (United States)

    Pazos-Couselo, Marcos; García-López, Jose Manuel; González-Rodríguez, Maria; Gude, Francisco; Mayán-Santos, Jose Manuel; Rodríguez-Segade, Santiago; Rodríguez-García, Javier; Casanueva, Felipe

    2015-10-01

    Hypoglycemia is a limiting factor in the achievement of strict glycemic control. The primary objective of this 9-week study was to determine the frequency of hypoglycemia in patients with stable insulin-treated type 2 diabetes mellitus by comparing self-monitored blood glucose (SMBG) measurement with continuous glucose monitoring (CGM). This was an observational prospective study. Included in the study were 63 stable, insulin-treated patients with type 2 diabetes. They were instructed to record 2 daily capillary blood glucose readings, pre- and/or postprandial, in a sequential way during 8 consecutive weeks. A CGM system was worn during an additional week. We evaluated the frequency of hypoglycemia using the 8-week SMBG profile and the 1 CGM week. SMBG revealed that 50% of the patients had experienced hypoglycemia. CGM found hypoglycemia in 59% of patients. Significantly higher percentages of hyperglycemic and hypoglycemic episodes were detected by CGM than by capillary blood glucose measurements (61.1% vs. 50.8%; p=0.047) and (3.8% vs. 1.7%; p=0.016); 33% of patients experienced nocturnal hypoglycemia, and 19% of patients who had no data concerning hypoglycemia recorded in the capillary blood glucose diary had experienced hypoglycemia as measured by CGM, and the hypoglycemia occurred mainly during the nocturnal period. In stable well-controlled, insulin-treated patients with type 2 diabetes, CGM showed higher numbers of hypoglycemic events than did SMBG, especially at night. CGM is a useful tool that provides clinically valuable information about glucose control in these patients. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  8. 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 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.

  9. 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....

  10. Gravity with Intermediate Goods Trade

    Directory of Open Access Journals (Sweden)

    Sujin Jang

    2017-12-01

    Full Text Available This paper derives the gravity equation with intermediate goods trade. We extend a standard monopolistic competition model to incorporate intermediate goods trade, and show that the gravity equation with intermediates trade is identical to the one without it except in that gross output should be used as the output measure instead of value added. We also show that the output elasticity of trade is significantly underestimated when value added is used as the output measure. This implies that with the conventional gravity equation, the contribution of output growth can be substantially underestimated and the role of trade costs reduction can be exaggerated in explaining trade expansion, as we demonstrate for the case of Korea's trade growth between 1995 and 2007.

  11. Larval helminths in intermediate hosts

    DEFF Research Database (Denmark)

    Fredensborg, Brian Lund; Poulin, R

    2005-01-01

    Density-dependent effects on parasite fitness have been documented from adult helminths in their definitive hosts. There have, however, been no studies on the cost of sharing an intermediate host with other parasites in terms of reduced adult parasite fecundity. Even if larval parasites suffer...... transmission to their bird definitive host by predation. In experimental infections, we found an intensity-dependent establishment success, with a decrease in the success rate of cercariae developing into infective metacercariae with an increasing dose of cercariae applied to each amphipod. In natural...... the two species. Our results thus indicate that the infracommunity of larval helminths in their intermediate host is interactive and that any density-dependent effect in the intermediate host may have lasting effects on individual parasite fitness....

  12. 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

    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...... diabetes who are prone to recurrent severe hypoglycemia with an insulin analogue regimen is cost-effective compared with a human insulin regimen....

  13. A Case of Inoperable Malignant Insulinoma with Resistant Hypoglycemia Who Experienced the Most Significant Clinical Improvement with Everolimus

    Directory of Open Access Journals (Sweden)

    Emre Bozkirli

    2013-01-01

    Full Text Available Metastatic insulinomas may sometimes present with recurrent life-threatening hypoglycemia episodes. Such patients usually fail to respond to various therapeutic agents which causes constant dextrose infusion requirement. Herein, we present a resistant case of inoperable malignant insulinoma who was treated with many therapeutic agents and interventions including somatostatin analogues, Yttrium-90 radioembolization, everolimus, radiotherapy, and chemoembolization. Close blood sugar monitorization during these therapies showed the most favourable response with everolimus. Everolimus treatment resulted in rapid improvement of hypoglycemia episodes, letting us discontinue dextrose infusion and discharge the patient. However, experience with everolimus in such patients is still limited, and more precise data can be obtained with the increasing use of this agent for neuroendocrine tumours.

  14. 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.

  15. Does Reducing Basal Insulin During Ramadan Fasting by Children and Adolescents with Type 1 Diabetes Decrease the Risk of Symptomatic Hypoglycemia?

    Science.gov (United States)

    Deeb, Asma; Al Qahtani, Nabras; Attia, Salima; Al Suwaidi, Hana; Nagelkerke, Nico

    2016-09-01

    Ramadan fasting by patients with type 1 diabetes might predispose them to hypoglycemia. There are no data on the optimal way of adjusting basal insulin during fasting. We aim at studying whether reducing basal insulin during Ramadan reduces the frequency of symptomatic hypoglycemia. We enrolled children and adolescents with type 1 diabetes who intended to fast during Ramadan. Logbooks were given to subjects to mark days fasted, symptomatic hypoglycemia, and dose of basal insulin on all days of Ramadan. Logbooks were examined. Glucometers and insulin pumps were downloaded. Seventy-five patients were enrolled. The age was 10.2-18.9 (14.5) years. Sixty-eight patients had results analyzed. Forty-one patients were on pumps, and 27 patients were on multiple daily injections (MDI). Mean HbA1c was 7.9 (1.2) and 8.4 (1.3) for the pump and the MDI, respectively (P = 0.007). Thirty-nine patients had hypoglycemia leading to breaking fast. The mean number of episodes of breaking fast was 3 (1-8). Thirty-five of the 68 patients had reduced basal insulin. The difference in the frequency of hypoglycemia in those who reduced/did not reduce insulin was not statistically significant (P > 0.10). Fifteen patients on MDI and 24 patients on pumps had at least one episode of breaking fast. Six and 18 of the patients on MDI and pumps, respectively, reduced basal insulin (P > 0.10). This is the first study examining the impact of reduction of basal insulin on hypoglycemia in adolescents. Reducing basal insulin during Ramadan fasting does not decrease the risk of symptomatic hypoglycemia. Use of the insulin pump does not appear to be different from MDI in the frequency of occurrence of hypoglycemia.

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

    Science.gov (United States)

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

    2018-03-07

    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.

  17. Chromium modulates expressions of neuronal plasticity markers and glial fibrillary acidic proteins in hypoglycemia-induced brain injury.

    Science.gov (United States)

    Sahin, Kazim; Tuzcu, Mehmet; Orhan, Cemal; Ali, Shakir; Sahin, Nurhan; Gencoglu, Hasan; Ozkan, Yusuf; Hayirli, Armagan; Gozel, Nevzat; Komorowski, James R

    2013-12-18

    This experiment investigated if chromium (Cr) as Cr-histidinate (CrHis) and Cr29 picolinate (CrPic) have a protective role in rats with hypoglycemia-induced brain injury, assessed by neuronal plasticity and regeneration potential. Male Sprague-Dawley rats were prospectively divided into 2 groups: control and hypoglycemic (induced by insulin administration, 15U/kg, i.p., n=56). Hypoglycemic rats were then received randomly 1) none, 2) dextrose (on the day of sampling), 3) CrHis, or 4) CrPic. Cr-chelates were delivered via drinking water (providing 8μg elemental Cr per day) for one week prior to the hypoglycemia induction. The expressions of neuroplasticity markers [neural cell adhesion molecule (NCAM), growth-associated protein-43 (GAP-43), glial fibrillary acidic protein (GFAP)], glucose transporters (GLUT), and nuclear transcription proteins [nuclear factor-kappa (NF-κB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and 4-hydroxyl nonenal (HNE)] were determined using Western blot. Hypoglycemia caused increases in the expressions of GLUT-1, GLUT-3, GFAP, NF-κB and HNE and decreases in the expression of NCAM's, GAP-43 and Nrf2 in the hippocampus, cerebellum, and cortex. Cr-chelates suppressed expressions of GLUTs, GFAP, NF-κB and HNE expressions and enhanced expressions of NCAM, GAP-43 and Nrf2, which were more notable for CrHis than for CrPic. In conclusion, hypoglycemia leads to cerebral injury and Cr-chelates, particularly CrHis have protective and regeneration potential in cerebral tissues through modulating neuroplasticity markers and nuclear transcription proteins as well as facilitating glucose transporters. © 2013.

  18. Chronic fetal hypoglycemia inhibits the later steps of stimulus-secretion coupling in pancreatic beta-cells.

    Science.gov (United States)

    Rozance, Paul J; Limesand, Sean W; Zerbe, Gary O; Hay, William W

    2007-05-01

    We measured the impact of chronic late gestation hypoglycemia on pancreatic islet structure and function to determine the cause of decreased insulin secretion in this sheep model of fetal nutrient deprivation. Late gestation hypoglycemia did not decrease pancreas weight, insulin content, beta-cell area, beta-cell mass, or islet size. The pancreatic islet isolation procedure selected a group of islets that were larger and had an increased proportion of beta-cells compared with islets measured in pancreatic sections, but there were no morphologic differences between islets isolated from control and hypoglycemic fetuses. The rates of glucose-stimulated pancreatic islet glucose utilization (126.2 +/- 25.3 pmol glucose.islet(-1).h(-1), hypoglycemic, vs. 93.5 +/- 5.5 pmol glucose.islet(-1).h(-1), control, P = 0.47) and oxidation (10.5 +/- 1.7 pmol glucose.islet(-1).h(-1), hypoglycemic, vs. 10.6 +/- 1.6 pmol glucose.islet(-1).h(-1), control) were not different in hypoglycemic fetuses compared with control fetuses. Chronic late gestation hypoglycemia decreased insulin secretion in isolated pancreatic islets by almost 70% in response to direct nonnutrient membrane depolarization and in response to increased extracellular calcium entry. beta-Cell ultrastructure was abnormal with markedly distended rough endoplasmic reticulum in three of the seven hypoglycemic fetuses studied, but in vitro analysis of hypoglycemic control islets showed no evidence that these changes represented endoplasmic reticulum stress, as measured by transcription of glucose regulatory protein-78 and processing of X-box binding protein-1. In conclusion, these studies show that chronic hypoglycemia in late gestation decreases insulin secretion by inhibiting the later steps of stimulus-secretion coupling after glucose metabolism, membrane depolarization, and calcium entry.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Recurrent Moderate Hypoglycemia Suppresses Brain-Derived Neurotrophic Factor Expression in the Prefrontal Cortex and Impairs Sensorimotor Gating in the Posthypoglycemic Period in Young Rats.

    Science.gov (United States)

    Rao, Raghavendra; Ennis, Kathleen; Mitchell, Eugena P; Tran, Phu V; Gewirtz, Jonathan C

    2016-01-01

    Recurrent hypoglycemia is common in infants and children. In developing rat models, recurrent moderate hypoglycemia leads to neuronal injury in the medial prefrontal cortex. To understand the effects beyond neuronal injury, 3-week-old male rats were subjected to 5 episodes of moderate hypoglycemia (blood glucose concentration, approx. 30 mg/dl for 90 min) once daily from postnatal day 24 to 28. Neuronal injury was determined using Fluoro-Jade B histochemistry on postnatal day 29. The effects on brain-derived neurotrophic factor (BDNF) and its cognate receptor, tyrosine kinase receptor B (TrkB) expression, which is critical for prefrontal cortex development, were determined on postnatal day 29 and at adulthood. The effects on prefrontal cortex-mediated function were determined by assessing the prepulse inhibition of the acoustic startle reflex on postnatal day 29 and 2 weeks later, and by testing for fear-potentiated startle at adulthood. Recurrent hypoglycemia led to neuronal injury confined primarily to the medial prefrontal cortex. BDNF/TrkB expression in the prefrontal cortex was suppressed on postnatal day 29 and was accompanied by lower prepulse inhibition, suggesting impaired sensorimotor gating. Following the cessation of recurrent hypoglycemia, the prepulse inhibition had recovered at 2 weeks. BDNF/TrkB expression in the prefrontal cortex had normalized and fear-potentiated startle was intact at adulthood. Recurrent moderate hypoglycemia during development has significant adverse effects on the prefrontal cortex in the posthypoglycemic period. © 2016 S. Karger AG, Basel.

  1. Intermediate Infrastructure Analyst | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The incumbent conducts research on technologies and tools that might enhance service delivery and where appropriate, makes recommendations to management. The Intermediate Infrastructure System Analyst provides leadership and direction to junior team members and functional direction to consultants and ...

  2. 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 (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.

  3. Eucaloric Ketogenic Diet Reduces Hypoglycemia and Inflammation in Mice with Endotoxemia.

    Science.gov (United States)

    Nandivada, Prathima; Fell, Gillian L; Pan, Amy H; Nose, Vania; Ling, Pei-Ra; Bistrian, Bruce R; Puder, Mark

    2016-06-01

    Dietary strategies to alter the immune response to acute inflammation have the potential to improve outcomes in critically ill patients. A eucaloric ketogenic diet (EKD), composed predominantly of fat with very small amounts of carbohydrate, can provide adequate caloric support while minimizing spikes in blood glucose and reducing oxidative stress. The purpose of this study was to evaluate the effects of an EKD on glycemic control and the inflammatory response after acute endotoxemia in mice. Mice received either an EKD or a carbohydrate-based control diet (CD) for 4 weeks. Animals subsequently underwent either a 2-h fast (postprandial) or an overnight fast (postabsorptive), and half of the animals in each diet group were randomized to receive either intraperitoneal lipopolysaccharide (1 mg/kg) or an equivalent volume of saline. Glycemic response, insulin resistance, inflammatory cytokine levels, and the expression of key inflammatory and metabolic genes were measured. After endotoxin challenge, hypoglycemia was more frequent in mice fed a CD than an EKD in the postprandial period. This was due in part to the preservation of hepatic glycogen stores despite endotoxin exposure and prolonged fasting in mice fed an EKD. Furthermore, mice fed the CD had higher levels of IL-6 and TNF-α in the postabsorptive period, with a fivefold higher expression of hepatic NFκB compared to mice fed the EKD in both fasting periods. These results suggest that the unique metabolic state induced by an EKD can alter the response to acute inflammation in mice.

  4. Metabolic acidosis, hypoglycemia, and severe myalgias: an attempt to mask urine drug screen results.

    Science.gov (United States)

    Arcinegas-Rodriguez, Silvana; Gaspers, Mary Glas; Lowe, Merlin Channing

    2011-04-01

    Adolescent use of illicit substances remains a significant problem. In attempts to hide their use of these substances, some are using Internet-recommended methods of masking these drugs on drug screens, potentially exposing the adolescent to severe and possibly dangerous adverse effects. We report a 16-year-old patient who ingested approximately 13 g (twenty-six 500-mg tablets) of niacin during a 48-hour period in an attempt to mask his use of tetrahydrocannabinol on an upcoming drug screen. He subsequently developed severe chest and abdominal pain as well as extreme diffuse myalgias (previously unreported in association with niacin use). In addition, he developed severe hypoglycemia, acidosis, transaminitis, and coagulopathy. He required significant fluid resuscitation and bicarbonate infusion. Over approximately 5 days his symptoms resolved and he ultimately did well. Given increasingly available home drug screens and the abundance of false information readily available to adolescents via the Internet regarding "masking" of drug use, it is likely that cases such as ours will become more prevalent. Pediatric emergency physicians and pediatricians should maintain a high suspicion for use of niacin or other substances to obscure detection of illicit substances when patients present with symptoms similar to those of our patient. Copyright © 2011 by Lippincott Williams & Wilkins

  5. Conundrum of elevated HbA1C and hypoglycemia-a rare cause.

    Science.gov (United States)

    Nanda, Sudip; Sharma, Shree Gopal; Bhatt, Surya Prakash; Pamula, John; Arastu, Mohammad I

    2008-05-01

    A white diabetic patient on insulin therapy presented with recurrent hypoglycemia despite very high glycosylated hemoglobin (HbA1c) values. Hemoglobin (Hb) variants, chemically modified Hb, and abnormalities of red cell turnover cause errors in HbA1c measurement. Widely prevalent Hb variants affecting HbA1c estimation include HbS and HbC in African Americans, HbE in southeast Asians, and carbamyl-Hb in uremic patients. In addition, there are at least 893 other Hb variants as of 2005, many of which affect HbA1c estimation. HbA1c values are also affected by methodology of estimation. Our patient had HbJ, which is rare amongst whites. The relationship between HbA1c values and mean plasma glucose allows estimation of expected HbA1c. Significant discrepancy between expected and measured HbA1c should be evaluated. Considering Hb variants, evaluating for the same and estimating HbA1c with the appropriate method under such circumstances are described. Numerous new or rare Hb variants will be diagnosed if suspicion is appropriately entertained.

  6. Severe Hypoglycemia and Cardiovascular or All-Cause Mortality in Patients with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Seon-Ah Cha

    2016-04-01

    Full Text Available BackgroundWe investigated the association between severe hypoglycemia (SH and the risk of cardiovascular (CV or all-cause mortality in patients with type 2 diabetes.MethodsThe study included 1,260 patients aged 25 to 75 years with type 2 diabetes from the Vincent Type 2 Diabetes Resgistry (VDR, who consecutively enrolled (n=1,260 from January 2000 to December 2010 and were followed up until May 2015 with a median follow-up time of 10.4 years. Primary outcomes were death from any cause or CV death. We investigated the association between the CV or all-cause mortality and various covariates using Cox proportional hazards regression analysis.ResultsAmong the 906 participants (71.9% who completed follow-up, 85 patients (9.4% had at least one episode of SH, and 86 patients (9.5% died (9.1 per 1,000 patient-years. Patients who had died were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline, as compared with surviving patients. The experience of SH was significantly associated with an increased risk of all-cause mortality (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.39 to 5.02; P=0.003 and CV mortality (HR, 6.34; 95% CI, 2.02 to 19.87; P=0.002 after adjusting for sex, age, diabetic duration, hypertension, mean glycosylated hemoglobin levels, diabetic nephropathy, lipid profiles, and insulin use.ConclusionWe found a strong association between SH and increased risk of all-cause and CV mortality in patients with type 2 diabetes.

  7. Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock.

    Science.gov (United States)

    Wang, Hao; Guan, Yuxia; Widlund, Anne Lykkegaard; Becker, Lance B; Baur, Joseph A; Reilly, Patrick M; Sims, Carrie A

    2014-12-01

    Hemorrhagic shock (HS) may contribute to organ failure, by profoundly altering mitochondrial function. Resveratrol (RSV), a naturally occurring polyphenol, has been shown to promote mitochondrial function and regulate glucose homeostasis in diabetes. We hypothesized that RSV during resuscitation would ameliorate HS-induced mitochondrial dysfunction and improve hyperglycemia following acute blood loss. With the use a decompensated HS model, male Long-Evans rats (n = 6 per group) were resuscitated with lactated Ringer's solution with or without RSV (30 mg/kg) and were killed before hemorrhage (sham), at severe shock, following resuscitation, and 18 hours after resuscitation. At each time point, the liver and kidney mitochondria were isolated to assess individual respiratory complexes (CI, CII, and CIV) and the production of reactive oxygen species (ROS). Blood samples were assayed for glucose, insulin, corticosterone, total glucagon-like peptide (GLP-1), glucagon, and serum cytokine levels. The Homeostatic Model Assessment-Insulin Resistance index was used to quantify insulin resistance. RSV supplementation following HS significantly improved mitochondrial function and decreased mitochondrial ROS production in both liver and kidney. RSV-treated animals had significantly lower blood glucose levels following resuscitation when compared with sham animals (116.0 ± 20.2 mg/dL vs. 227.7 ± 8.3 mg/dL, p GLP-1 levels (385.8 ± 56.6 ng/mL vs. 187.3 ± 11.1 ng/mL, p effect on plasma corticosterone, glucagon, or cytokine levels. Resuscitation with RSV restores mitochondrial function and decreases insulin resistance but may be associated with increased hypoglycemia. The observed antiglycemic effects of RSV may be mediated by decreased mitochondrial ROS and increased GLP-1 secretion.

  8. Maternal diabetes and neonatal macrosomia. I. Postpartum maternal hemoglobin A1c levels and neonatal hypoglycemia.

    Science.gov (United States)

    Brans, Y W; Huff, R W; Shannon, D L; Hunter, M A

    1982-10-01

    Hemoglobin A1c (HgbA1c) levels were determined within 24 hours after delivery in 88 nondiabetic and 73 diabetic women belonging to White's classes A to D. Diet-controlled gestational diabetic women had mean (+/- SE) Hgb A1c levels similar to those of nondiabetics (5.8 +/- 0.18% vs 5.7 +/- 0.08%). Mean Hgb A1c levels were higher in insulin-requiring gestational (6.4 +/- 0.20%, P less than .05) and permanent (6.5 +/- 0.27%, P less than .05) diabetics than in nondiabetics. The proportions of subjects with levels above the normal range were also larger in the insulin-requiring groups. Mean Hgb A1c levels and the proportions of abnormally high levels were similar for mothers of macrosomic and of normally grown neonates in the nondiabetic as well as in the various diabetes groups. There was no correlation between maternal Hgb A1c level and neonatal birth weight, either real or relative. There were also no statistically significant differences in mean Hgb A1c levels between mothers of neonates with or without hypoglycemia within four hours of birth. Hgb A1c measurement did not permit differentiation between those mothers of macrosomic neonates who were diabetic and those who were not. In conclusion, although Hgb A1c level has been shown to reflect diabetic control, our data suggest that it may not be reliable as an indicator of fine tuning during the third trimester of pregnancy or as a predictor of the effects of diabetes on the fetus.

  9. 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

  10. ESL intermediate/advanced writing

    CERN Document Server

    Munoz Page, Mary Ellen; Jaskiewicz, Mary

    2011-01-01

    Master ESL (English as a Second Language) Writing with the study guide designed for non-native speakers of English. Skill-building lessons relevant to today's topics help ESL students write complete sentences, paragraphs, and even multi-paragraph essays. It's perfect for classroom use or self-guided writing preparation.DETAILS- Intermediate drills for improving skills with parallel structure, mood, correct shifting errors & dangling participles- Advanced essay drills focusing on narrative, descriptive, process, reaction, comparison and contrast- Superb preparation for students taking the TOEFL

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Subcutaneous glucagon infusion and continuous glucose monitoring enable effective management of hypoglycemia in a patient with IGF-2-producing hemangiopericytoma

    OpenAIRE

    Buras, Eric D.; Weatherup, Emily; Wyckoff, Jennifer

    2018-01-01

    Background Ectopic insulin-like growth factor (IGF)-2 production is a rare complication of an array of epithelial and mesenchymal tumors, and can clinically manifest as life-threatening hypoglycemia. Case presentation A 49-year-old woman with 13-year history of metastatic hemangiopericytoma, previously treated with multiple rounds of chemotherapy and palliative radiation, presented to the emergency department after a hypoglycemic seizure. On arrival, glucose was 18 mg/dL (1.0 mmol/L) and requ...

  15. Intermediate neutron detection by thermoluminescence

    International Nuclear Information System (INIS)

    Santos, E.N. dos; Muccillo, R.

    1979-01-01

    Thermoluminescent (TL) studies were carried out in cold-pressed CaSO 4 :Dy + Dy 2 O 3 + KCl and CaF 2 + Dy 2 O 3 + KCl polycrystalline samples exposed to mixed neutron-gamma fields, for the detection of intermediate neutrons which is based on the evaluation of the TL signal of the specimens stored for 24 hours after being exposed to a mixed neutron-gamma field and thermally annealed to erase the total radiation-induced TL. The addition of Dy 2 O 3 to CaSO 4 :Dy in the proportion 1:2 increased the neutron response by a factor of 160 relative to that of CaSO 4 :Dy. 180 mg of CaSO 4 :Dy + Dy 2 O 3 + KCl in the proportion 2:1:3 showed to be an appropriate detector of intermediate neutrons; the minimum detectable fluence was estimated to be 3.5 x 10 5 neutrons/cm 2 . (Author) [pt

  16. Conditional Tissue-Specific Foxa2 Ablation in Mouse Pancreas Causes Hyperinsulinemic Hypoglycemia: RETRACTED.

    Science.gov (United States)

    Wu, Zengbin; Fei, Aihua; Liu, Yingbin; Pan, Shuming

    The forkhead/winged helix transcription factor Foxa2 is a major upstream regulator of Pdx1, a transcription factor necessary for pancreatic development. In the present study, we conditionally knocked out Foxa2 in Pdx1-expressing domain and further analyzed the contribution of Foxa2 to α- and β-cell development and the effect of Foxa2 deletion on plasma insulin, glucagon, and glucose levels. Homozygous pdx1 Foxa2 mice and heterozygous pdx1 Foxa2 mice were generated by homologous recombination using a Foxa2 gene-targeting vector. α- and β-cell mass was examined by immunofluorescence microscopy. Plasma glucose, insulin, and plasma were measured at postnatal day 10. For pdx1 lineage tracing studies, heterozygous pdx1 Foxa2 EYFP and homozygous pdx1 Foxa2 EYFP mice were used. Our immunofluorescence analysis revealed that in the pancreas sections of the homozygous mutant mice, Foxa2 was virtually absent from non-β cells and its expression almost exclusively coincided with remnant β cells. The density of both α and β cells apparently decreased in the pancreas of the heterozygous mutant mice and in the pancreas of the homozygous mutant mice, α cells lost its predominance and β cells increased proportionally. Direct Pdx1 cell lineage tracing revealed that, on embryonic day 18.5, in the homozygous mutant mice, Pdx1 expression coincided almost exclusively with that of insulin-secreting β cells. Chemiluminescence assays revealed that heterozygous pdx1 Foxa2 mice had significantly lower insulin levels than control mice (P Foxa2 mice and control mice (P > 0.05). Chemiluminescence assays also showed that Foxa2 deletion significantly depressed plasma glucagon levels in both homozygous pdx1 Foxa2 mice and heterozygous pdx1 Foxa2 mice (P Foxa2 mice compared with control mice (P Foxa2 ablation leads to an imbalance in β/α ratio, profound hypoglucagonemia, inappropriate hyperinsulinemia, and hypoglycemia in mice. Our conditional tissue-specific Foxa2 ablation mouse model

  17. Conditional Tissue-Specific Foxa2 Ablation in Mouse Pancreas Causes Hyperinsulinemic Hypoglycemia.

    Science.gov (United States)

    Wu, Zengbin; Fei, Aihua; Liu, Yingbin; Pan, Shuming

    The forkhead/winged helix transcription factor Foxa2 is a major upstream regulator of Pdx1, a transcription factor necessary for pancreatic development. In the present study, we conditionally knocked out Foxa2 in Pdx1-expressing domain and further analyzed the contribution of Foxa2 to α- and β-cell development and the effect of Foxa2 deletion on plasma insulin, glucagon, and glucose levels. Homozygous pdx1 Foxa2 mice and heterozygous pdx1 Foxa2 mice were generated by homologous recombination using a Foxa2 gene-targeting vector. α- and β-cell mass was examined by immunofluorescence microscopy. Plasma glucose, insulin, and plasma were measured at postnatal day 10. For pdx1 lineage tracing studies, heterozygous pdx1 Foxa2 EYFP and homozygous pdx1 Foxa2 EYFP mice were used. Our immunofluorescence analysis revealed that in the pancreas sections of the homozygous mutant mice, Foxa2 was virtually absent from non-β cells and its expression almost exclusively coincided with remnant β cells. The density of both α and β cells apparently decreased in the pancreas of the heterozygous mutant mice and in the pancreas of the homozygous mutant mice, α cells lost its predominance and β cells increased proportionally. Direct Pdx1 cell lineage tracing revealed that, on embryonic day 18.5, in the homozygous mutant mice, Pdx1 expression coincided almost exclusively with that of insulin-secreting β cells. Chemiluminescence assays revealed that heterozygous pdx1 Foxa2 mice had significantly lower insulin levels than control mice (P Foxa2 mice and control mice (P > 0.05). Chemiluminescence assays also showed that Foxa2 deletion significantly depressed plasma glucagon levels in both homozygous pdx1 Foxa2 mice and heterozygous pdx1 Foxa2 mice (P Foxa2 mice compared with control mice (P Foxa2 ablation leads to an imbalance in β/α ratio, profound hypoglucagonemia, inappropriate hyperinsulinemia, and hypoglycemia in mice. Our conditional tissue-specific Foxa2 ablation mouse model

  18. Dogs Can Be Successfully Trained to Alert to Hypoglycemia Samples from Patients with Type 1 Diabetes.

    Science.gov (United States)

    Hardin, Dana S; Anderson, Wesley; Cattet, Jennifer

    2015-12-01

    Hypoglycemia (Hypo) is the most common side effect of insulin therapy in people with type 1 diabetes (T1D). Over time, patients with T1D become unaware of signs and symptoms of Hypo. Hypo unawareness leads to morbidity and mortality. Diabetes alert dogs (DADs) represent a unique way to help patients with Hypo unawareness. Our group has previously presented data in abstract form which demonstrates the sensitivity and specificity of DADS. The purpose of our current study is to expand evaluation of DAD sensitivity and specificity using a method that reduces the possibility of trainer bias. We evaluated 6 dogs aging 1-10 years old who had received an average of 6 months of training for Hypo alert using positive training methods. Perspiration samples were collected from patients during Hypo (BG 46-65 mg/dL) and normoglycemia (BG 85-136 mg/dl) and were used in training. These samples were placed in glass vials which were then placed into 7 steel cans (1 Hypo, 2 normal, 4 blank) randomly placed by roll of a dice. The dogs alerted by either sitting in front of, or pushing, the can containing the Hypo sample. Dogs were rewarded for appropriate recognition of the Hypo samples using a food treat via a remote control dispenser. The results were videotaped and statistically evaluated for sensitivity (proportion of lows correctly alerted, "true positive rate") and specificity (proportion of blanks + normal samples not alerted, "true negative rate") calculated after pooling data across all trials for all dogs. All DADs displayed statistically significant (p value <0.05) greater sensitivity (min 50.0%-max 87.5%) to detect the Hypo sample than the expected random correct alert of 14%. Specificity ranged from a min of 89.6% to a max of 97.9% (expected rate is not defined in this scenario). Our results suggest that properly trained DADs can successfully recognize and alert to Hypo in an in vitro setting using smell alone.

  19. 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

    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.......Glucagon-like peptide 1 (GLP-1) is a proglucagon derivative secreted primarily from the L-cells of the small intestinal mucosa in response to the ingestion of meals. GLP-1 stimulates insulin secretion and inhibits glucagon secretion. It has previously been shown that intravenous or subcutaneous...... 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...

  20. 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.

  1. Intermediate processes in nuclear reactions

    International Nuclear Information System (INIS)

    Petrovici, M.

    1983-01-01

    The main results presented here cannot be interpreted in terms of the direct reaction model or the statistical models and one can more or less explicitely use some nuclear configurations for their interpretation. The first chapter deals with the so-called second order intermediate structures observed in the elastic and inelastic proton scattering on 66 Zn and 70 Ge targets in the energetic regions of some isobaric analog resonances. A formal theory for their interpretation is developed and the comparison with the experimental data is presented. New experimental results on the resonant structures observed in the elastic and inelastic scattering of 12 C on 24 Mg are presented in the second chapter. Detailed statistical analysis and their interpretation is presented too. Charge equilibration in deep inelastic collisions is the main subject of the third chapter. The experimental results obtained by the 98 Mo + 154 Sm collision at 12 MeV/n, a quantum treatment of a damped harmonic oscillator and the comparison with the experimental data are given. In the last chapter, some results on the existence of two other processes which could candidate to be involved in the main topic are presented. Those processes are: the fast fragmentation and preequilibrium charged particles emission. All these processes originate in the excitation of some simple configurations which can be seen on ''doorway'' states (''Hallway'' in the case of the second intermediate structures). The coupling of these states to other more complicated excitation modes of the nuclei and to outgoing channel=gives the possibility to study the nuclear dynamics. This justifies the interest for their detailed theoretical and experimental investigations. (author)

  2. Co-expression of c-Fos with oestradiol receptor α or somatostatin in the arcuate nucleus, ventromedial nucleus and medial preoptic area in the follicular phase of intact ewes: alteration after insulin-induced hypoglycaemia.

    Science.gov (United States)

    Fergani, C; Routly, Je; Jones, Dn; Pickavance, Lc; Smith, Rf; Dobson, H

    2015-02-01

    The aim of this study was to investigate how acute insulin-induced hypoglycaemia (IIH) alters the activity of cells containing oestradiol receptor α (ERα) or somatostatin (SST) in the arcuate nucleus (ARC) and ventromedial nucleus (VMN), and ERα cells in the medial preoptic area (mPOA) of intact ewes. Follicular phases were synchronized with progesterone vaginal pessaries. Control animals were killed at 0 h or 31 h (n = 5 and 6, respectively) after progesterone withdrawal (PW; time zero). At 28 h, five other animals received insulin (INS; 4 iu/kg) and were subsequently killed at 31 h. Hypothalamic sections were immunostained for ERα or SST each with c-Fos, a marker of neuronal transcriptional activation. Insulin did not alter the percentage of activated ERα cells in the ARC; however, it appeared visually that two insulin-treated animals (INS responders, with no LH surge) had an increase in the VMN (from 32 to 78%) and a decrease in the mPOA (from 40 to 12%) compared to no increase in the two INS non-responders (with an LH surge). The percentage of activated SST cells in the ARC was greater in all four insulin-treated animals (from 10 to 60%), whereas it was visually estimated that activated SST cells in the VMN increased only in the two insulin responders (from 10 to 70%). From these results, we suggest that IIH stimulates SST activation in the ARC as part of the glucose-sensing mechanism but ERα activation is unaffected in this region. We present evidence to support a hypothesis that disruption of the GnRH/LH surge may occur in insulin responders via a mechanism that involves, at least in part, SST cell activation in the VMN along with decreased ERα cell activation in the mPOA. © 2014 Blackwell Verlag GmbH.

  3. Insulin induces relaxation and decreases hydrogen peroxide-induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium-activated potassium channels and L-arginine/nitric oxide pathways.

    Directory of Open Access Journals (Sweden)

    Lissette Cabrera

    2016-11-01

    Full Text Available Insulin induces relaxation in umbilical veins, increasing the expression of human amino acid transporter 1 (hCAT-1 and nitric oxide synthesis (NO in human umbilical vein endothelial cells (HUVECs. Short-term effects of insulin on vasculature have been reported in healthy subjects and cell cultures; however, its mechanisms remain unknown. The aim of this study was to characterize the effect of acute incubation with insulin on the regulation of vascular tone of placental vasculature. HUVECs and chorionic vein rings were isolated from normal pregnancies. The effect of insulin on NO synthesis, L-arginine transport and hCAT-1 abundance was measured in HUVECs. Isometric tension induced by U46619 (thromboxane A2 analogue or hydrogen peroxide (H2O2 were measured in vessels previously incubated 30 min with insulin and/or the following pharmacological inhibitors: tetraethylammonium (KCa channels, iberiotoxin (BKCa channels, genistein (tyrosine kinases and wortmannin (phosphatidylinositol 3-kinase. Insulin increases L-arginine transport and NO synthesis in HUVECs. In the placenta, this hormone caused relaxation of the chorionic vein and reduced perfusion pressure in placental cotyledons. In vessels pre-incubated with insulin, the constriction evoked by H2O2 and U46619 was attenuated and the effect on H2O2-induced constriction was blocked with tetraethylammonium and iberiotoxin, but not with genistein or wortmannin. Insulin rapidly dilates the placental vasculature through a mechanism involving activity of BKCa channels and L-arginine/NO pathway in endothelial cells. This phenomenon is related to quick increases of hCAT-1 abundance and higher capacity of endothelial cells to take up L-arginine and generate NO.

  4. RHIZOME AND DISCOURSE OF INTERMEDIALITY

    Directory of Open Access Journals (Sweden)

    Л Н Синельникова

    2017-12-01

    Full Text Available Rhizomaticity is a strategy and a regularity of text creation in a lot of modern commu-nicative discourse practices. What remains urgent is the problem of the systematic interdisciplinary de-scription of texts whose structure and language qualities are determined by the signs of the rhizome - a concept of post-modern philosophy introduced into the scientific field by the French philosopher Gilles Deleuze and the psychotherapist Félix Guattari (Deleuze, Guattari 1996. The rhizome (Fr. rhizome - rootstock, tuber, bulb, mycelium possesses the following qualities: it is non-linear, open and directed towards the unpredictability of discourse transformations through the possibilities of structure development in any direction; there is no centre or periphery in the rhizome, and any discourse element can become ‘a vital structure’ for text-creation. The rhizome does not have non-intersecting boundaries; and in the space of the rhizomatic discourse environment, an increase of reality facets takes place, non-standard associative con-nections appear, multiplication effects are formed, which create new meanings. Rhizomaticity is the quality of texts being organised by the laws of rhizomatic logic (V.F. Sharkov 2007, by the terms of which ‘su-perposition’ of discourses can take place, a transition from one semiotic system to another. The article makes an attempt to correlate the qualities of the rhizome with the signs of the intermedia discourse, which is built on the semiotic interaction of different media. The moving lines of the rhizome, its ‘branch-ing’ qualities can be found in poetic texts, in the evaluating segments of political discourse, in advertising discourse, in internet communications, which represent rhizomorphic environments. An analysis of examples from these spheres has shown that the rhizomatic approach opens new facets of intermediality. The author uses the methods of discourse analysis to prove that the openness and non

  5. On financial equilibrium with intermediation costs

    DEFF Research Database (Denmark)

    Markeprand, Tobias Ejnar

    2008-01-01

    This paper studies the set of competitive equilibria in financial economies with intermediation costs. We consider an arbitrary dividend structure, which includes options and equity with limited liabilities.We show a general existence result and upper-hemi continuity of the equilibrium...... correspondence. Finally, we prove that when intermediation costs approach zero, unbounded volume of asset trades is a necessary and sufficient condition, provided that, there is no financial equilibrium without intermediation costs....

  6. Biocatalytic Synthesis of Chiral Pharmaceutical Intermediates

    Directory of Open Access Journals (Sweden)

    Ramesh N. Patel

    2004-01-01

    Full Text Available The production of single enantiomers of drug intermediates has become increasingly important in the pharmaceutical industry. Chiral intermediates and fine chemicals are in high demand from both the pharmaceutical and agrochemical industries for the preparation of bulk drug substances and agricultural products. The enormous potential of microorganisms and enzymes for the transformation of synthetic chemicals with high chemo-, regio- and enantioselectivities has been demonstrated. In this article, biocatalytic processes are described for the synthesis of chiral pharmaceutical intermediates.

  7. Experiments in intermediate energy physics

    Energy Technology Data Exchange (ETDEWEB)

    Dehnhard, D.

    2003-02-28

    Research in experimental nuclear physics was done from 1979 to 2002 primarily at intermediate energy facilities that provide pion, proton, and kaon beams. Particularly successful has been the work at the Los Alamos Meson Physics Facility (LAMPF) on unraveling the neutron and proton contributions to nuclear ground state and transition densities. This work was done on a wide variety of nuclei and with great detail on the carbon, oxygen, and helium isotopes. Some of the investigations involved the use of polarized targets which allowed the extraction of information on the spin-dependent part of the triangle-nucleon interaction. At the Indiana University Cyclotron Facility (IUCF) we studied proton-induced charge exchange reactions with results of importance to astrophysics and the nuclear few-body problem. During the first few years, the analysis of heavy-ion nucleus scattering data that had been taken prior to 1979 was completed. During the last few years we created hypernuclei by use of a kaon beam at Brookhaven National Laboratory (BNL) and an electron beam at Jefferson Laboratory (JLab). The data taken at BNL for a study of the non-mesonic weak decay of the A particle in a nucleus are still under analysis by our collaborators. The work at JLab resulted in the best resolution hypernuclear spectra measured thus far with magnetic spectrometers.

  8. Compact Intermediate-Temperature Fuel Cells

    National Research Council Canada - National Science Library

    Sun, Yipeng

    2003-01-01

    In Phase I, we demonstrate the feasibility of making supported electronically insulating, proton conducting inorganic thin films on metal hydride foils for intermediate temperature fuel cell electrolytes...

  9. Insulin pumps in pediatric routine care improve long-term metabolic control without increasing the risk of hypoglycemia.

    Science.gov (United States)

    Hanas, Ragnar; Adolfsson, Peter

    2006-02-01

    Although continuous subcutaneous insulin infusion (CSII) has been used in pediatric practice for >20 yr, the technique is not widely used in many countries. The aim of this non-randomized population-based study was to evaluate CSII in routine pediatric care. In a 1-yr cross-sectional evaluation, 27/89 patients (30.3%, age 7-21 yr) used pumps (two during the night only), the others 4-6 injections/day. In patients with >2 yr of diabetes, pump users had higher HbA1c (8.9+/-1.0 vs. 8.2+/-1.6%, p=0.04), less insulin/24 h (0.9+/-0.1 vs. 1.0+/-0.2 U/kg, p=0.002), and longer diabetes duration (p=0.02). The higher HbA1c is explained by 67% of pump patients having high HbA1c (>8.5%) as the major indication for CSII. The overall incidence of severe hypoglycemia was 31.5/100 patient years, 40.3 for injection therapy, and 11.1 for pump therapy (p=not significant). The incidence of severe hypoglycemia with unconsciousness was 12.9/100 patient years and with seizures 9.7 for injection therapy, whereas no children on pumps experienced these complications during the cross-sectional study year. We had no admissions for ketoacidosis in either group during this year. The pump patients were followed for 5 yr after pump start. Two stopped using the pump after 2 and 3 yr. For the patients with high HbA1c as indication, mean HbA1c the year before pump was 9.5%. Mean HbA1c during the first year with pump was lowered to 8.9% (p=0.019), the second year 8.6% (p=0.017), the third year 8.6 (p=0.012), the fourth year 8.7 (p=0.062), and the fifth year 8.9% (p=0.28). We found six cases of ketoacidosis corresponding to 4.7/100 patient years. In conclusion, we found a long-term lowering of HbA1c after starting CSII in a pediatric population, decreased frequency of severe hypoglycemia, and a low risk of ketoacidosis.

  10. Continuous Glucose Monitoring After Gastric Bypass to Evaluate the Glucose Variability After a Low-Carbohydrate Diet and to Determine Hypoglycemia.

    Science.gov (United States)

    Nielsen, Joan Bach; Abild, Caroline Bruun; Pedersen, Ane Mathilde; Pedersen, Steen Bønløkke; Richelsen, Bjørn

    2016-09-01

    Roux-en-Y gastric bypass (RYGB) alters glucose metabolism and can cause postprandial hypoglycemia. Continuous glucose monitoring (CGM) has been proposed as an evaluation tool in hypoglycemic RYGB individuals. The objective of this study is to investigate the use of CGM in clinical decision-making including diagnosing hypoglycemia and evaluating treatment effects. Furthermore, we aim to assess its accuracy in RYGB-operated individuals. Thirteen RYGB individuals with symptomatic hypoglycemia and 13 asymptomatic RYGB individuals underwent CGM for 5 days. During this period, a mixed-meal test with concomitant plasma glucose (PG) measurements was performed. Furthermore, the RYGB individuals followed a low-carbohydrate diet (LCD) for 1 day and maintained their ordinary diet (OD) for the rest of the period. LCD reduced the CGM-determined glycemic variability of the mean interstitial fluid glucose (IFG) significantly compared to OD (p RYGB individuals and for displaying dietary effects on reducing this glycemic variability, including hypoglycemic events. In RYGB individuals, CGM-measured IFG overestimated the real glucose value by about 1 mmol/l in the hypoglycemic range. This should be taken into consideration if CGM is used to diagnose hypoglycemia after RYGB.

  11. Metabolic and Neurologic Sequelae in a Patient with Long-Standing Anorexia Nervosa Who Presented with Septic Shock and Deep Hypoglycemia

    NARCIS (Netherlands)

    de Jager, Corine M.; Hoekstra, Miriam; Nijsten, Maarten W. N.; Oude Lansink, Annemieke; Ismael, Farouq

    2011-01-01

    Objective: To report the case of a 48-year female with chronic remitting anorexia nervosa who was found comatose at home and admitted to our hospital with a deep hypoglycemia (glucose level 0.6 mmol/L; 11 mg/dL) and septic shock secondary to a bilateral pneumonia. Method: Case report. Results: After

  12. Insulin induces airway smooth muscle contraction

    NARCIS (Netherlands)

    Schaafsma, D.; Gosens, R.; Ris, J. M.; Zaagsma, J.; Meurs, H.; Nelemans, S. A.

    Background and purpose: Recently, the use of inhaled insulin formulations for the treatment of type I and type II diabetes has been approved in Europe and in the United States. For regular use, it is critical that airway function remains unimpaired in response to insulin exposure. Experimental

  13. Nuclear structure at intermediate energies

    International Nuclear Information System (INIS)

    Bonner, B.E.; Mutchler, G.S.

    1991-01-01

    The theme that unites the sometimes seemingly disparate experiments undertaken by the Bonner Lab Medium Energy Group is a determination to understand in detail the many facets and manifestations of the strong interaction, that which is now referred to as nonperturbative QCD. Whether we are investigating the question of just what does carry the spin of baryons, or the extent of the validity of the SU(6) wavefunctions for the excited hyperons (as will be measured in their radiative decays in our CEBAF experiment), or questions associated with the formation of a new state of matter predicted by QCD (the subject of our BNL experiments E810, E854, as well as our approved experiment at RHIC), -- all these projects share this common goal. Our other experiments represent different approaches to the same broad undertaking. LAMPF E1097 will provide definitive answers to the question of the spin dependence of the inelastic channel of pion production in the n-p interaction. FNAL E683 may well open a new field of investigation in nuclear physics: that of just how quarks and gluons interact with nuclear matter as they transverse nuclei of different sizes. In most all of the experiments mentioned above, the Bonner Lab Group is playing major leadership roles as well as doing a big fraction of the hard work that such experiments require. We use many of the facilities that are unavailable to the intermediate energy physics community and we use our expertise to design and fabricate the detectors and instrumentation that are required to perform the measurements which we decide to do

  14. Nuclear structure at intermediate energies

    Energy Technology Data Exchange (ETDEWEB)

    Bonner, B.E.; Mutchler, G.S.

    1991-09-30

    The theme that unites the sometimes seemingly disparate experiments undertaken by the Bonner Lab Medium Energy Group is a determination to understand in detail the many facets and manifestations of the strong interaction, that which is now referred to as nonperturbative QCD. Whether we are investigating the question of just what does carry the spin of baryons, or the extent of the validity of the SU(6) wavefunctions for the excited hyperons (as will be measured in their radiative decays in our CEBAF experiment), or questions associated with the formation of a new state of matter predicted by QCD (the subject of our BNL experiments E810, E854, as well as our approved experiment at RHIC), -- all these projects share this common goal. Our other experiments represent different approaches to the same broad undertaking. LAMPF E1097 will provide definitive answers to the question of the spin dependence of the inelastic channel of pion production in the n-p interaction. FNAL E683 may well open a new field of investigation in nuclear physics: that of just how quarks and gluons interact with nuclear matter as they transverse nuclei of different sizes. In most all of the experiments mentioned above, the Bonner Lab Group is playing major leadership roles as well as doing a big fraction of the hard work that such experiments require. We use many of the facilities that are unavailable to the intermediate energy physics community and we use our expertise to design and fabricate the detectors and instrumentation that are required to perform the measurements which we decide to do.

  15. 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

    BACKGROUND: To examine the relation between self-reported hypoglycemic events, worries about these episodes, and the burden of diabetes in adults with diabetes and family members from The Netherlands. METHODS: As part of the second multinational Diabetes Attitudes, Wishes and Needs (DAWN2) study......, 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......: In total, 41% of people with diabetes and 56% of family members considered diabetes at least somewhat of a burden. In people with diabetes, diabetes burden was independently associated with self-reported current insulin use (fully adjusted OR = 2.75, 95% CI 1.49-5.10), self-reported frequent non...

  16. Anemia causes hypoglycemia in intensive care unit patients due to error in single-channel glucometers: methods of reducing patient risk.

    Science.gov (United States)

    Pidcoke, Heather F; Wade, Charles E; Mann, Elizabeth A; Salinas, Jose; Cohee, Brian M; Holcomb, John B; Wolf, Steven E

    2010-02-01

    Intensive insulin therapy in the critically ill reduces mortality but carries the risk of increased hypoglycemia. Point-of-care blood glucose analysis is standard; however, anemia causes falsely high values and potentially masks hypoglycemia. Permissive anemia is practiced routinely in most intensive care units. We hypothesized that point-of-care glucometer error due to anemia is prevalent, can be corrected mathematically, and correction uncovers occult hypoglycemia during intensive insulin therapy. The study has both retrospective and prospective phases. We reviewed data to verify the presence of systematic error, determine the source of error, and establish the prevalence of anemia. We confirmed our findings by reproducing the error in an in vitro model. Prospective data were used to develop a correction formula validated by the Monte Carlo method. Correction was implemented in a burn intensive care unit and results were evaluated after 9 mos. Burn and trauma intensive care units at a single research institution. Samples for in vitro studies were taken from healthy volunteers. Samples for formula development were from critically ill patients who received intensive insulin therapy. Insulin doses were calculated based on predicted serum glucose values from corrected point-of-care glucometer measurements. Time-matched point-of-care glucose, laboratory glucose, and hematocrit values. We previously found that anemia (hematocrit error in glucometer measurements. The error was correctible with a mathematical formula developed and validated, using prospectively collected data. Error of uncorrected point-of-care glucose ranged from 19% to 29% (p < .001), improving to < or = 5% after mathematical correction of prospective data. Comparison of data pairs before and after correction formula implementation demonstrated a 78% decrease in the prevalence of hypoglycemia in critically ill and anemic patients treated with insulin and tight glucose control (p < .001). A mathematical

  17. Impact of the "Diabetes Interactive Diary" telemedicine system on metabolic control, risk of hypoglycemia, and quality of life: a randomized clinical trial in type 1 diabetes.

    Science.gov (United States)

    Rossi, Maria Chiara; Nicolucci, Antonio; Lucisano, Giuseppe; Pellegrini, Fabio; Di Bartolo, Paolo; Miselli, Valerio; Anichini, Roberto; Vespasiani, Giacomo

    2013-08-01

    Telemedicine systems based on mobile phones represent new promising educational tools. The "Diabetes Interactive Diary" (DID) is a carbohydrate/bolus calculator promoting the patient-physician communication via short message service. This study aimed to compare the efficacy of the DID versus usual care on metabolic control, hypoglycemia, and quality of life. Patients with type 1 diabetes on a basal:bolus regimen with insulin glargine and insulin glulisine, not previously educated on carbohydrate (CHO) counting, were randomized to DID (Group A; n=63) or traditional education (Group B; n=64). Generalized hierarchical linear regression models for repeated measures were applied to compare changes between groups. Incidence of hypoglycemia was compared using Poisson regression models. Of 127 patients (age, 36.9±10.5 years; diabetes duration, 16.3±9.3 years), 15 (11.8%) dropped out. After 6 months, hemoglobin A1c (HbA1c) levels decreased by -0.49±0.11 in Group A and -0.48±0.11 in Group B (P=0.73). Group A showed a 86% lower risk of grade 2 hypoglycemia than Group B. Compared with usual care, DID improved the "perceived frequency of hyperglycemic episodes" scale of the Diabetes Treatment Satisfaction Questionnaire and the "social relations" and the "fear of hypoglycemia" dimensions of the Diabetes Specific Quality of Life Scale. Results obtained with DID markedly differ among patients and centers. DID is no more effective than traditional CHO counting education in reducing HbA1c levels. DID reduces the risk of moderate/severe hypoglycemia and improves quality of life. A better understanding of patients' and healthcare professionals' attitudes associated with an effective care supported by technology is essential to avoid waste of resources.

  18. 19 CFR 122.84 - Intermediate airport.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Intermediate airport. 122.84 Section 122.84... Intermediate airport. (a) Application. The provisions of this section apply at any U.S. airport to which an... aircraft arrives at the next airport, the aircraft commander or agent shall make entry by filing the: (1...

  19. Gasoline Engine Mechanics. Performance Objectives. Intermediate Course.

    Science.gov (United States)

    Jones, Marion

    Several intermediate performance objectives and corresponding criterion measures are listed for each of six terminal objectives presented in this curriculum guide for an intermediate gasoline engine mechanics course at the secondary level. (For the beginning course guide see CE 010 947.) The materials were developed for a two-semester (2 hour…

  20. Some Intermediate-Level Violin Concertos.

    Science.gov (United States)

    Abramson, Michael

    1997-01-01

    Contends that many violin students attempt difficult concertos before they are technically or musically prepared. Identifies a variety of concertos at the intermediate and advanced intermediate-level for students to study and master before attempting the advanced works by Bach and Mozart. Includes concertos by Vivaldi, Leclair, Viotti, Haydn,…

  1. Automotive Body Repair. Performance Objectives. Intermediate Course.

    Science.gov (United States)

    Lang, Thomas

    Several intermediate performance objectives and corresponding criterion measures are listed for each of 10 terminal objectives for an intermediate automotive body repair and refinishing course. The materials were developed for a two-semester (3 hours daily) course for specialized classrooms, shop, and practical experiences designed to enable the…

  2. 39 CFR 3001.39 - Intermediate decisions.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Intermediate decisions. 3001.39 Section 3001.39 Postal Service POSTAL REGULATORY COMMISSION PERSONNEL RULES OF PRACTICE AND PROCEDURE Rules of General Applicability § 3001.39 Intermediate decisions. (a) Initial decision by presiding officer. In any proceedings in...

  3. Brazil : Interest Rates and Intermediation Spreads

    OpenAIRE

    World Bank

    2006-01-01

    This study sheds light on the analytical and policy issues regarding the high intermediation spread in Brazil, focusing on its determinants, the reasons for its persistence, and its impact on the real economy, especially on access to finance for Brazilian firms. The key contention of the analysis is that high intermediation spreads are a symptom of underlying problems; as such, spreads constitute ...

  4. Identification of outliers and positive deviants for healthcare improvement: looking for high performers in hypoglycemia safety in patients with diabetes

    Directory of Open Access Journals (Sweden)

    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.

  5. Identification of outliers and positive deviants for healthcare improvement: looking for high performers in hypoglycemia safety in patients with diabetes.

    Science.gov (United States)

    Wilson, Brigid; Tseng, Chin-Lin; Soroka, Orysya; Pogach, Leonard M; Aron, David C

    2017-11-16

    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. 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. 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 performing facilities for overtreatment had higher rates of undertreatment (A1c > 9%) than VA average in the population of patients at high risk for hypoglycemia. 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.

  6. 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)

  7. Epithelial Intermediate Filaments: Guardians against Microbial Infection?

    Directory of Open Access Journals (Sweden)

    Florian Geisler

    2016-06-01

    Full Text Available Intermediate filaments are abundant cytoskeletal components of epithelial tissues. They have been implicated in overall stress protection. A hitherto poorly investigated area of research is the function of intermediate filaments as a barrier to microbial infection. This review summarizes the accumulating knowledge about this interaction. It first emphasizes the unique spatial organization of the keratin intermediate filament cytoskeleton in different epithelial tissues to protect the organism against microbial insults. We then present examples of direct interaction between viral, bacterial, and parasitic proteins and the intermediate filament system and describe how this affects the microbe-host interaction by modulating the epithelial cytoskeleton, the progression of infection, and host response. These observations not only provide novel insights into the dynamics and function of intermediate filaments but also indicate future avenues to combat microbial infection.

  8. Effect of Intermediate Hosts on Emerging Zoonoses.

    Science.gov (United States)

    Cui, Jing-An; Chen, Fangyuan; Fan, Shengjie

    2017-08-01

    Most emerging zoonotic pathogens originate from animals. They can directly infect humans through natural reservoirs or indirectly through intermediate hosts. As a bridge, an intermediate host plays different roles in the transmission of zoonotic pathogens. In this study, we present three types of pathogen transmission to evaluate the effect of intermediate hosts on emerging zoonotic diseases in human epidemics. These types are identified as follows: TYPE 1, pathogen transmission without an intermediate host for comparison; TYPE 2, pathogen transmission with an intermediate host as an amplifier; and TYPE 3, pathogen transmission with an intermediate host as a vessel for genetic variation. In addition, we established three mathematical models to elucidate the mechanisms underlying zoonotic disease transmission according to these three types. Stability analysis indicated that the existence of intermediate hosts increased the difficulty of controlling zoonotic diseases because of more difficult conditions to satisfy for the disease to die out. The human epidemic would die out under the following conditions: TYPE 1: [Formula: see text] and [Formula: see text]; TYPE 2: [Formula: see text], [Formula: see text], and [Formula: see text]; and TYPE 3: [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] Simulation with similar parameters demonstrated that intermediate hosts could change the peak time and number of infected humans during a human epidemic; intermediate hosts also exerted different effects on controlling the prevalence of a human epidemic with natural reservoirs in different periods, which is important in addressing problems in public health. Monitoring and controlling the number of natural reservoirs and intermediate hosts at the right time would successfully manage and prevent the prevalence of emerging zoonoses in humans.

  9. Language in use intermediate : classroom book

    CERN Document Server

    Doff, Adrian

    1995-01-01

    ach of the four levels comprises about 80 hours of class work, with additional time for the self-study work. The Teacher's Book contains all the pages from the Classroom Book, with interleaved teaching notes including optional activities to cater for different abilities. There is a video to accompany the Beginner, Pre-intermediate and Intermediate levels. Each video contains eight stimulating and entertaining short programmes, as well as a booklet of photocopiable activities. Free test material is available in booklet and web format for Beginner and Pre-intermediate levels. Visit www.cambridge.org/elt/liu or contact your local Cambridge University Press representative.

  10. Language in use intermediate : teacher's book

    CERN Document Server

    Doff, Adrian

    1998-01-01

    Each of the four levels comprises about 80 hours of class work, with additional time for the self-study work. The Teacher's Book contains all the pages from the Classroom Book, with interleaved teaching notes including optional activities to cater for different abilities. There is a video to accompany the Beginner, Pre-intermediate and Intermediate levels. Each video contains eight stimulating and entertaining short programmes, as well as a booklet of photocopiable activities. Free test material is available in booklet and web format for Beginner and Pre-intermediate levels. Visit www.cambridge.org/elt/liu or contact your local Cambridge University Press representative.

  11. Intermedial Strategies of Memory in Contemporary Novels

    DEFF Research Database (Denmark)

    Tanderup, Sara

    2014-01-01

    , and Judd Morrissey and drawing on the theoretical perspectives of N. Katherine Hayles (media studies) and Andreas Huyssen (cultural memory studies), Tanderup argues that recent intermedial novels reflect a certain nostalgia celebrating and remembering the book as a visual and material object in the age......In her article "Intermedial Strategies and Memory in Contemporary Novels" Sara Tanderup discusses a tendency in contemporary literature towards combining intermedial experiments with a thematic preoccupation with memory and trauma. Analyzing selected works by Steven Hall, Jonathan Safran Foer...... of digital media while also highlighting the influence of new media on our cultural understanding and representation of memory and the past....

  12. Intermediate/Advanced Research Design and Statistics

    Science.gov (United States)

    Ploutz-Snyder, Robert

    2009-01-01

    The purpose of this module is To provide Institutional Researchers (IRs) with an understanding of the principles of advanced research design and the intermediate/advanced statistical procedures consistent with such designs

  13. The deterioration of intermediate moisture foods

    Science.gov (United States)

    Labruza, T. P.

    1971-01-01

    Deteriorative reactions are low and food quality high if intermediate moisture content of a food is held at a water activity of 0.6 to 0.75. Information is of interest to food processing and packaging industry.

  14. Proposed changes in intermediate pipe break criteria

    International Nuclear Information System (INIS)

    Schmitz, R.P.

    1984-01-01

    Bechtel Power Corporation proposed to the US NRC in 1983 that the NRC eliminate from their criteria all intermediate breaks. Bechtel's rationale for the proposal and support for their position are presented

  15. MNE Entrepreneurial Capabilities at Intermediate Levels

    DEFF Research Database (Denmark)

    Hoenen, Anne K.; Nell, Phillip Christopher; Ambos, Björn

    2014-01-01

    at intermediate geographical levels differ from local subsidiaries and global corporate headquarters, and why those differences are important. We illustrate our arguments using data on European regional headquarters (RHQs). We find that RHQs' entrepreneurial capabilities depend on their external embeddedness...

  16. Directional spread parameter at intermediate water depth

    Digital Repository Service at National Institute of Oceanography (India)

    SanilKumar, V.; Deo, M.C.; Anand, N.M.; AshokKumar, K.

    The characteristics of directional spread parameters at intermediate water depth are investigated based on a cosine power '2s' directional spreading model. This is based on wave measurements carried out using a Datawell directional waverider buoy...

  17. Intermediality, Architecture, and the Politics of Urbanity

    OpenAIRE

    Tortosa Garrigós, Virgilio

    2011-01-01

    In his article "Intermediality, Architecture, and the Politics of Urbanity" Virgilio Tortosa Garrigós discusses aspects of the exponential development of large cities, the neoliberal economy, and the "spectacle" of architecture in the context of intermediality. With the connivance between land speculators and politicians — which has led not only to the loss of spatial identity but to irreversible pollution and geographic degradation — urbanity is epitomized on the Mediterranean coast line. In...

  18. Intermediate Inflation or Late Time Acceleration?

    International Nuclear Information System (INIS)

    Sanyal, A.K.

    2008-01-01

    The expansion rate of intermediate inflation lies between the exponential and power law expansion but corresponding accelerated expansion does not start at the onset of cosmological evolution. Present study of intermediate inflation reveals that it admits scaling solution and has got a natural exit form it at a later epoch of cosmic evolution, leading to late time acceleration. The corresponding scalar field responsible for such feature is also found to behave as a tracker field for gravity with canonical kinetic term.

  19. Higher order antibunching in intermediate states

    International Nuclear Information System (INIS)

    Verma, Amit; Sharma, Navneet K.; Pathak, Anirban

    2008-01-01

    Since the introduction of binomial state as an intermediate state, different intermediate states have been proposed. Different nonclassical effects have also been reported in these intermediate states. But till now higher order antibunching is predicted in only one type of intermediate state, which is known as shadowed negative binomial state. Recently we have shown that the higher order antibunching is not a rare phenomenon [P. Gupta, P. Pandey, A. Pathak, J. Phys. B 39 (2006) 1137]. To establish our earlier claim further, here we have shown that the higher order antibunching can be seen in different intermediate states, such as binomial state, reciprocal binomial state, hypergeometric state, generalized binomial state, negative binomial state and photon added coherent state. We have studied the possibility of observing the higher order subpoissonian photon statistics in different limits of intermediate states. The effects of different control parameters on the depth of non classicality have also been studied in this connection and it has been shown that the depth of nonclassicality can be tuned by controlling various physical parameters

  20. Associations of Systemic Diseases with Intermediate Uveitis.

    Science.gov (United States)

    Shoughy, Samir S; Kozak, Igor; Tabbara, Khalid F

    2016-01-01

    To determine the associations of systemic diseases with intermediate uveitis. The medical records of 50 consecutive cases with intermediate uveitis referred to The Eye Center in Riyadh, Saudi Arabia, were reviewed. Age- and sex-matched patients without uveitis served as controls. Patients had complete ophthalmic and medical examinations. There were 27 male and 23 female patients. Mean age was 29 years with a range of 5-62 years. Overall, 21 cases (42%) had systemic disorders associated with intermediate uveitis and 29 cases (58%) had no associated systemic disease. A total of 11 patients (22%) had asthma, 4 (8%) had multiple sclerosis, 3 (6%) had presumed ocular tuberculosis, 1 (2%) had inflammatory bowel disease, 1 (2%) had non-Hodgkin lymphoma and 1 (2%) had sarcoidosis. Evidence of systemic disease was found in 50 (5%) of the 1,000 control subjects. Bronchial asthma was found in 37 patients (3.7 %), multiple sclerosis in 9 patients (0.9%), inflammatory bowel disease in 3 patients (0.3%), and tuberculosis in 1 patient (0.1%). None of the control patients had sarcoidosis or lymphoma. There were statistically significant associations between intermediate uveitis and bronchial asthma (p = 0.0001), multiple sclerosis (p = 0.003) and tuberculosis (p = 0.0005). Bronchial asthma and multiple sclerosis were the most frequently encountered systemic diseases associated with intermediate uveitis in our patient population. Patients with intermediate uveitis should undergo careful history-taking and investigations to rule out associated systemic illness.

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

    DEFF Research Database (Denmark)

    Sorensen, J. S.; Johannesen, J.; Pociot, F.

    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...... 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....../mol]; P 0.2 nmol/L (mean +/- SE: 1.07 +/- 0.02 vs. 0.93 +/- 0.07 units/kg/day; P diabetes. Children with RBF...

  2. Shwachman-Diamond syndrome presenting with early ichthyosis, associated dermal and epidermal intracellular lipid droplets, hypoglycemia, and later distinctive clinical SDS phenotype.

    Science.gov (United States)

    Scalais, Emmanuel; Connerotte, Anne-Catherine; Despontin, Karine; Biver, Armand; Ceuterick-de Groote, Chantal; Alders, Marielle; Kolivras, Athanassios; Hachem, Jean-Pierre; De Meirleir, Linda

    2016-07-01

    Shwachman-Diamond syndrome (SDS) is a recessive ribosomopathy, characterized by bone marrow failure and exocrine pancreatic insufficiency (ePI) often associated with neurodevelopmental and skeletal abnormalities. The aim of this report is to describe a SDS patient with early ichthyosis associated with dermal and epidermal intracellular lipid droplets (iLDs), hypoglycemia and later a distinctive clinical SDS phenotype. At 3 months of age, she had ichthyosis, growth retardation, and failure to thrive. She had not cytopenia. Ultrasonography (US) showed pancreatic diffuse high echogenicity. Subsequently fasting hypoketotic hypoglycemia occurred without permanent hepatomegaly or hyperlipidemia. Continuous gavage feeding was followed by clinical improvement including ichthyosis and hypoglycemia. After 14 months of age, she developed persistent neutropenia and ePI consistent with SDS. The ichthyotic skin biopsy, performed at 5 months of age, disclosed iLDs in all epidermal layers, in melanocytes, eccrine sweat glands, Schwann cells and dermal fibroblasts. These iLDs were reminiscent of those described in Dorfman-Chanarin syndrome (DCS) or Wolman's disease. Both LIPA and CGI-58 analysis did not revealed pathogenic mutation. By sequencing SBDS, a compound heterozygous for a previously reported gene mutation (c.258 + 2T>C) and a novel mutation (c.284T>G) were found. Defective SBDS may hypothetically interfere as in DCS, with neutral lipid metabolism and play a role in the SDS phenotype such as ichthyosis with dermal and epidermal iLDs and hypoglycemia. This interference with neutral lipid metabolism must most likely occur in the cytoplasm compartment as in DCS and not in the lysosomal compartment as in Wolman's disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Persistent and severe hypoglycemia associated with trimethoprim-sulfamethoxazole in a frail diabetic man on polypharmacy: A case report and literature review
.

    Science.gov (United States)

    Rossio, Raffaella; Arcudi, Sara; Peyvandi, Flora; Piconi, Stefania

    2018-02-01

    Trimethoprim-sulfamethoxazole (co-trimoxazole) is a commonly used broad-spectrum antibiotic, but it can be associated with potentially serious adverse effects, often not recognized by clinicians. This is a relevant problem in elderly patients, who are particularly susceptible to adverse drug reactions. Moreover, multiple medications taken by older people increase the risk for adverse drug reactions and drug-drug interactions. We report the case of an 85-year-old man with diabetes mellitus who attended the emergency room with severe hypoglycemia that persisted despite multiple intravenous bolus doses and continuous infusion of glucose. He needed hospital admission to stabilize glycemia. The patient, a nursing home resident, was being treated with co-trimoxazole for an uncomplicated urinary tract infection, but was also taking multiple additional drugs for his co-morbidities. After co-trimoxazole was discontinued, plasma glucose levels slowly stabilized within the normal range. A diagnosis of prolonged and refractory hypoglycemia induced mainly by the antimicrobial agent was made, with additional contribution from multiple other drugs. No further episodes of hypoglycemia occurred during the next 6 months of follow-up. This case study illustrates once more the critical importance of prescription appropriateness in elderly patients with multiple morbidities in terms of type and dosage of drugs, in order to avoid serious adverse reactions.
.

  4. No evidence of hypoglycemia or hypotension in older adults during 6 months of flax lignan supplementation in a randomized controlled trial: a safety evaluation.

    Science.gov (United States)

    Billinsky, Jennifer; Glew, Riley A; Cornish, Stephen M; Whiting, Susan J; Thorpe, Lilian U; Alcorn, Jane; Paus-Jenssen, Lisa; Hadjistavropoulos, Thomas; Chilibeck, Philip D

    2013-06-01

    The natural health product, BeneFlax, is a standardized flaxseed [Linum usitatissimum L. (Linaceae)] lignan enriched product with evidence of product quality and known quantity of the bioactive component, lignan. The acceptance of this natural health product for its various health benefits requires greater evidence of its safety in the general population. We determined whether flaxseed lignan causes clinical hypoglycemia or hypotension in healthy older adults as an important aspect of safety. Participants aged 49-87 years were randomized in a double-blind trial to receive flaxseed lignan (543 mg/day in BeneFlax) or placebo while completing a 6-month walking program. The 94 participants who completed the study were stratified by age (Controlling for sex and body mass index covariates resulted in no observed differences between plasma glucose or blood pressure measurements between treatment or age groups (p > 0.05). No incidents of hypoglycemia or hypotension were observed during BeneFlax treatment, suggesting that 543 mg falls at or below the no observable adverse effect level (NOAEL). These data suggest the flaxseed lignan product BeneFlax does not pose a risk of hypoglycemia or hypotension in healthy adults aged 49-87 years.

  5. Predicting the 6-month risk of severe hypoglycemia among adults with diabetes: Development and external validation of a prediction model.

    Science.gov (United States)

    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.

  6. Genetic deletion of Rheb1 in the brain reduces food intake and causes hypoglycemia with altered peripheral metabolism.

    Science.gov (United States)

    Yang, Wanchun; Jiang, Wanxiang; Luo, Liping; Bu, Jicheng; Pang, Dejiang; Wei, Jing; Du, Chongyangzi; Xia, Xiaoqiang; Cui, Yiyuan; Liu, Shuang; Mao, Qing; Chen, Mina

    2014-01-21

    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.

  7. Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism

    Science.gov (United States)

    Yang, Wanchun; Jiang, Wanxiang; Luo, Liping; Bu, Jicheng; Pang, Dejiang; Wei, Jing; Du, Chongyangzi; Xia, Xiaoqiang; Cui, Yiyuan; Liu, Shuang; Mao, Qing; Chen, Mina

    2014-01-01

    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. PMID:24451134

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism

    Directory of Open Access Journals (Sweden)

    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.

  10. Partially folded intermediates during trypsinogen denaturation

    Directory of Open Access Journals (Sweden)

    Martins N.F.

    1999-01-01

    Full Text Available The equilibrium unfolding of bovine trypsinogen was studied by circular dichroism, differential spectra and size exclusion HPLC. The change in free energy of denaturation was = 6.99 ± 1.40 kcal/mol for guanidine hydrochloride and = 6.37 ± 0.57 kcal/mol for urea. Satisfactory fits of equilibrium unfolding transitions required a three-state model involving an intermediate in addition to the native and unfolded forms. Size exclusion HPLC allowed the detection of an intermediate population of trypsinogen whose Stokes radii varied from 24.1 ± 0.4 Å to 26.0 ± 0.3 Å for 1.5 M and 2.5 M guanidine hydrochloride, respectively. During urea denaturation, the range of Stokes radii varied from 23.9 ± 0.3 Å to 25.7 ± 0.6 Å for 4.0 M and 6.0 M urea, respectively. Maximal intrinsic fluorescence was observed at about 3.8 M urea with 8-aniline-1-naphthalene sulfonate (ANS binding. These experimental data indicate that the unfolding of bovine trypsinogen is not a simple transition and suggest that the equilibrium intermediate population comprises one intermediate that may be characterized as a molten globule. To obtain further insight by studying intermediates representing different stages of unfolding, we hope to gain a better understanding of the complex interrelations between protein conformation and energetics.

  11. The ARES High-level Intermediate Representation

    Energy Technology Data Exchange (ETDEWEB)

    Moss, Nicholas David [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-03-03

    The LLVM intermediate representation (IR) lacks semantic constructs for depicting common high-performance operations such as parallel and concurrent execution, communication and synchronization. Currently, representing such semantics in LLVM requires either extending the intermediate form (a signi cant undertaking) or the use of ad hoc indirect means such as encoding them as intrinsics and/or the use of metadata constructs. In this paper we discuss a work in progress to explore the design and implementation of a new compilation stage and associated high-level intermediate form that is placed between the abstract syntax tree and when it is lowered to LLVM's IR. This highlevel representation is a superset of LLVM IR and supports the direct representation of these common parallel computing constructs along with the infrastructure for supporting analysis and transformation passes on this representation.

  12. 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.

    Science.gov (United States)

    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.

  13. Intermediate-energy nuclear chemistry workshop

    Energy Technology Data Exchange (ETDEWEB)

    Butler, G.W.; Giesler, G.C.; Liu, L.C.; Dropesky, B.J.; Knight, J.D.; Lucero, F.; Orth, C.J.

    1981-05-01

    This report contains the proceedings of the LAMPF Intermediate-Energy Nuclear Chemistry Workshop held in Los Alamos, New Mexico, June 23-27, 1980. The first two days of the Workshop were devoted to invited review talks highlighting current experimental and theoretical research activities in intermediate-energy nuclear chemistry and physics. Working panels representing major topic areas carried out indepth appraisals of present research and formulated recommendations for future research directions. The major topic areas were Pion-Nucleus Reactions, Nucleon-Nucleus Reactions and Nuclei Far from Stability, Mesonic Atoms, Exotic Interactions, New Theoretical Approaches, and New Experimental Techniques and New Nuclear Chemistry Facilities.

  14. Intermediate-energy nuclear chemistry workshop

    International Nuclear Information System (INIS)

    Butler, G.W.; Giesler, G.C.; Liu, L.C.; Dropesky, B.J.; Knight, J.D.; Lucero, F.; Orth, C.J.

    1981-05-01

    This report contains the proceedings of the LAMPF Intermediate-Energy Nuclear Chemistry Workshop held in Los Alamos, New Mexico, June 23-27, 1980. The first two days of the Workshop were devoted to invited review talks highlighting current experimental and theoretical research activities in intermediate-energy nuclear chemistry and physics. Working panels representing major topic areas carried out indepth appraisals of present research and formulated recommendations for future research directions. The major topic areas were Pion-Nucleus Reactions, Nucleon-Nucleus Reactions and Nuclei Far from Stability, Mesonic Atoms, Exotic Interactions, New Theoretical Approaches, and New Experimental Techniques and New Nuclear Chemistry Facilities

  15. Governance-Default Risk Relationship and the Demand for Intermediated and Non-Intermediated Debt

    Directory of Open Access Journals (Sweden)

    Husam Aldamen

    2012-09-01

    Full Text Available This paper explores the impact of corporate governance on the demand for intermediated debt (asset finance, bank debt, non-bank private debt and non-intermediated debt (public debt in the Australian debt market. Relative to other countries the Australian debt market is characterised by higher proportions of intermediated or private debt with a lower inherent level of information asymmetry in that private lenders have greater access to financial information (Gray, Koh & Tong 2009. Our firm level, cross-sectional evidence suggests that higher corporate governance impacts demand for debt via the mitigation of default risk. However, this relationship is not uniform across all debt types. Intermediated debt such as bank and asset finance debt are more responsive to changes in governance-default risk relationship than non-bank and non-intermediated debt. The implication is that a firm’s demand for different debt types will reflect its governance-default risk profile.

  16. Fostering teamwork in an intermediate care unit.

    Science.gov (United States)

    Spence, Heather; Cappleman, Julia

    2011-06-01

    The government has emphasised that, to deliver high quality, integrated care, staff must work across organisational boundaries using a team approach so that everyone works towards the same goals. This article describes how one NHS-managed intermediate care unit has integrated care staff employed by the independent sector.

  17. Essays in corporate finance and financial intermediation

    NARCIS (Netherlands)

    Kempf, Elisabeth

    2016-01-01

    This thesis consists of three chapters in corporate finance and financial intermediation. The first two chapters explore sources of incentives and learning for finance professionals. Specifically, the first chapter studies how the option to go work for an investment bank affects the incentives of

  18. 34 CFR 200.17 - Intermediate goals.

    Science.gov (United States)

    2010-07-01

    ..., DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE DISADVANTAGED Improving Basic.... Each State must establish intermediate goals that increase in equal increments over the period covered by the timeline under § 200.15 as follows: (a) The first incremental increase must take effect not...

  19. Trusted intermediating agents in electronic trade networks

    NARCIS (Netherlands)

    T.B. Klos (Tomas); F. Alkemade (Floortje)

    2005-01-01

    htmlabstract Electronic commerce and trading of information goods significantly impact the role of intermediaries: consumers can bypass intermediating agents by forming direct links to producers. One reason that traditional intermediaries can still make a profit, is that they have more knowledge of

  20. Intermediates and Generic Convergence to Equilibria

    DEFF Research Database (Denmark)

    Marcondes de Freitas, Michael; Wiuf, Carsten; Feliu, Elisenda

    2017-01-01

    Known graphical conditions for the generic and global convergence to equilibria of the dynamical system arising from a reaction network are shown to be invariant under the so-called successive removal of intermediates, a systematic procedure to simplify the network, making the graphical condition...

  1. Financial intermediation with credit constrained agents

    Czech Academy of Sciences Publication Activity Database

    Boháček, Radim

    2007-01-01

    Roč. 29, č. 4 (2007), s. 741-759 ISSN 0164-0704 R&D Projects: GA AV ČR IAA700850602 Institutional research plan: CEZ:AV0Z70850503 Keywords : financial intermediation * occupational choice * general equilibrium Subject RIV: AH - Economics Impact factor: 0.360, year: 2007

  2. What Should be Taught in Intermediate Macroeconomics?

    Science.gov (United States)

    de Araujo, Pedro; O'Sullivan, Roisin; Simpson, Nicole B.

    2013-01-01

    A lack of consensus remains on what should form the theoretical core of the undergraduate intermediate macroeconomic course. In determining how to deal with the Keynesian/classical divide, instructors must decide whether to follow the modern approach of building macroeconomic relationships from micro foundations, or to use the traditional approach…

  3. Interaction between Biomphalaria pfeifferi, the snail intermediate ...

    African Journals Online (AJOL)

    Biological control of snail intermediate host of human schistosome parasites has been suggested. In this study, the effect of Indoplanobis exustus a planorbid snail and possible competitor snail of Biomphalaria pfeifferi on the fecundity and growth rate of the later was evaluated. The results showed a significant difference in ...

  4. Bridge: Intelligent Tutoring with Intermediate Representations

    Science.gov (United States)

    1988-05-01

    Research and Development Center and Psychology Department University of Pittsburgh Pittsburgh, PA. 15260 The Artificial Intelligence and Psychology...problem never introduces more than one unfamiliar plan. Inteligent Tutoring With Intermediate Representations - Bonar and Cunniigbam 4 You must have a... Inteligent Tutoring With ntermediate Representations - Bonar and Cunningham 7 The requirements are specified at four differcnt levels, corresponding to

  5. Intermediality and politics in theatre and performance

    NARCIS (Netherlands)

    Dapp, G.S.

    2013-01-01

    This dissertation applies the concepts of intermediality and politics to five performances by Rimini Protokoll, Christoph Schlingensief, and Igneous, and analyzes the implications that emerge on both a significational and a theoretical level. Based on the specific mediality involved, it argues that

  6. Changes to the Intermediate Accounting Course Sequence

    Science.gov (United States)

    Davidson, Lesley H.; Francisco, William H.

    2009-01-01

    There is an ever-growing amount of information that must be covered in Intermediate Accounting courses. Due to recent accounting standards and the implementation of IFRS this trend is likely to continue. This report incorporates the results of a recent survey to examine the trend of spending more course time to cover this additional material.…

  7. Unraveling Intermediate Filaments : The super resolution solution

    NARCIS (Netherlands)

    Nahidiazar, L.

    2017-01-01

    Intermediate Filaments (IFs) carry out major functions in cells. Several diseases have been associated with malfunctioning IFs in the cells and among them are certain sub types of cancer. To determine the structure and organization of IFs, we have used Single Molecule Localization Microscopy (SMLM)

  8. Intermediate state trapping of a voltage sensor

    DEFF Research Database (Denmark)

    Lacroix, Jérôme J; Pless, Stephan Alexander; Maragliano, Luca

    2012-01-01

    transition pathway determined using the string method. The experimental results and computational analysis suggest that the phenotype of I241W may originate in the formation of a hydrogen bond between the indole nitrogen atom and the backbone carbonyl of R2. This work provides new information on intermediate...... states in voltage-gated ion channels with an approach that produces minimum chemical perturbation....

  9. Intuitionistic Rules : Admissible Rules of Intermediate Logics

    NARCIS (Netherlands)

    Goudsmit, J.P.

    2015-01-01

    In this thesis, we investigate the admissible rules of intermediate logics. On the one hand, one can characterize the admissibility of rules in certain logic, and on the other hand, one can characterize logics through their admissible rules. We take both approaches, and reach new results in both

  10. Intermediate Systems Analyst | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The intermediate Systems Analyst will bring to the System Development Group the necessary skills to understand in depth the architecture of Oracle to allow better design and implementation of new and enhanced information systems and applications. The incumbent will take full responsibility for the ITM division's ...

  11. Software Testing An ISEB Intermediate Certificate

    CERN Document Server

    Hambling, Brian

    2009-01-01

    Covering testing fundamentals, reviews, testing and risk, test management and test analysis, this book helps newly qualified software testers to learn the skills and techniques to take them to the next level. Written by leading authors in the field, this is the only official textbook of the ISEB Intermediate Certificate in Software Testing.

  12. Bismuth phosphates as intermediate temperature proton conductors

    DEFF Research Database (Denmark)

    Huang, Yunjie; Christensen, Erik; Shuai, Qin

    2017-01-01

    Proton conducting electrolyte materials operational in the intermediate temperature range of 200-400 °C are of special interest for applications in fuel cells and water electrolysers. Bismuth phosphates in forms of polycrystalline powders and amorphous glasses are synthesized and investigated...

  13. Design and rationale of the IN CONTROL trial: the effects of real-time continuous glucose monitoring on glycemia and quality of life in patients with type 1 diabetes mellitus and impaired awareness of hypoglycemia.

    Science.gov (United States)

    van Beers, Cornelis A J; Kleijer, Susanne J; Serné, Erik H; Geelhoed-Duijvestijn, Petronella H; Snoek, Frank J; Kramer, Mark H H; Diamant, Michaela

    2015-08-21

    Hypoglycemia is the main side effect of intensified insulin therapy in type 1 diabetes and recognized as a limitation in achieving glycemic targets. Patients with impaired awareness of hypoglycemia have a threefold to sixfold increased risk of severe hypoglycemia. Real-time continuous glucose monitoring may help patients with type 1 diabetes to achieve better glycemic control with less hypoglycemic episodes. Accordingly, one may hypothesize that particularly type 1 diabetes mellitus patients with impaired awareness of hypoglycemia will profit most from this technology with improvements in their quality of life. However, this has not yet been established. This trial aims to study the effect of real-time continuous glucose monitoring on glycemia and quality of life specifically in type 1 diabetes mellitus patients with established impaired awareness of hypoglycemia. This is a two-center, randomized, cross-over trial with a 12-week wash-out period in between intervention periods. A total of 52 type 1 diabetes mellitus patients with impaired awareness of hypoglycemia according to Gold et al. criteria will be randomized to receive real-time continuous glucose monitoring or blinded continuous glucose monitoring for 16 weeks. After a wash-out period, patients will cross over to the other intervention. The primary outcome measure is time spent in euglycemia. Secondary outcomes include (diabetes-specific) markers of quality of life and other glycemic variables. It remains unclear whether patients with type 1 diabetes and impaired awareness of hypoglycemia benefit from real-time continuous glucose monitoring in real-life. This study will provide insight into the potential benefits of real-time continuous glucose monitoring in this patient population. Clinicaltrials.gov: NCT01787903.

  14. 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.

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

    Science.gov (United States)

    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.

  16. One-Anastomosis Jejunal Interposition with Gastric Remnant Resection (Branco-Zorron Switch) for Severe Recurrent Hyperinsulinemic Hypoglycemia after Gastric Bypass for Morbid Obesity.

    Science.gov (United States)

    Zorron, Ricardo; Branco, Alcides; Sampaio, Jose; Bothe, Claudia; Junghans, Tido; Rasim, Gyurdzhan; Pratschke, Johann; Guel-Klein, Safak

    2017-04-01

    The anatomical and physiological changes after Roux-en-Y gastric bypass for morbid obesity can lead to severe hyperinsulinemic hypoglycemia with neuroglycopenia in a small percentage of patients. The exact physiologic mechanism is not completely understood. Surgical reversal to the original anatomy and distal or total pancreatectomy are current therapeutic options to reverse the hypoglycemic effect, with substantial associated morbidity. Our group reports a pilot clinical series of a novel surgical technique using one-anastomosis jejunal interposition with gastric remnant resection (Branco-Zorron Switch). Patients with severe symptomatic hyperinsulinemic hypoglycemia refractory to conservative therapy were treated using the technique. The procedure started with resection of the remnant stomach close to pylorus. The alimentary limb was sectioned at 20 cm from the gastrojejunal anastomosis, and the rest of the alimentary limb was resected until the Y-Roux anastomosis. A hand-sutured anastomosis was then performed with the proximal alimentary limb and the remnant antrum. Four patients were successfully submitted to the procedure with reversal of the symptomatology and normalization of insulin levels, postprandial glucose levels, and oral glucose tolerance test, with a mean follow-up of 24.3 months. Mean operative time was 188 min, and patients recovered without postoperative complications. Patients suffering from severe hyperinsulinemic hypoglycemia after gastric bypass may be efficiently treated by this innovative procedure, avoiding extreme surgical therapy such as pancreatectomy or restoring the gastric anatomy, while still maintaining sustained weight loss. Studies with larger series and longer follow-up are still needed to define the role of this therapy in managing this entity.

  17. Hypoglycemia is associated with increased worry and lower quality of life among patients with type 2 diabetes treated with oral antihyperglycemic agents in the Asia-Pacific region.

    Science.gov (United States)

    Sheu, Wayne H-H; Ji, Li-Nong; Nitiyanant, Wannee; Baik, Sei Hyun; Yin, Donald; Mavros, Panagiotis; Chan, Siew-Pheng

    2012-05-01

    We examined the relationship of hypoglycemic symptoms with health-related quality of life and worry about hypoglycemia among type 2 diabetic patients using oral antihyperglycemic agents (AHA) in the Asia-Pacific region. A total of 2257 type 2 diabetic patients with at least 6 months of oral AHA were enrolled in China, Korea, Malaysia, Thailand, and Taiwan. Quality of life was measured with the EuroQol Visual Analog Scale (EQ-VAS) and EuroQol-5 Dimensions questionnaire (EQ-5D), and worry about hypoglycemia with the worry subscale of the Hypoglycemic Fear Survey-II (HFS). The mean (SD) age was 58.7 (10.2) years and HbA(1c) was 7.5% (1.5). The proportion of patients with an HbA(1c) <6.5% and <7% was 24.9% and 41.8%, respectively. Hypoglycemic symptoms in the prior 6 months were reported by 35.8% of patients. Mean scores on the EQ-VAS and the EQ-5D were significantly lower for patients who had hypoglycemic symptoms compared to those who did not (73.6 vs. 76.9, p<0.001; 0.88 vs. 0.90, p<0.0001, respectively), whereas mean score on the HFS was significantly higher (12.5 vs. 6.3, p<0.001). In multivariate models, hypoglycemic symptoms were independently associated with scores on the EQ-5D, EQ-VAS, and HFS (all p ≤ 0.01-0.001). Symptom severity was positively associated with fear of hypoglycemia (all p ≤ 0.001). Hypoglycemic symptoms were associated with reduced quality of life and increased patient worry in patients with type 2 diabetes treated with AHA. Copyright © 2012. Published by Elsevier Ireland Ltd.

  18. Opening the Black Box of Intermediation

    DEFF Research Database (Denmark)

    Nowinska, Agnieszka

    ) and at the interfirm level (between partners and within alliances and associations).The tentative results show that both of these levels are important in defining the intermediating firms' business models and in answering their environmental threats and in building up competitive advantage. The paper ends with a short......This paper attempts to answer how external environmental factors affect intermediating firms within the maritime industry - the middlemen that plays a very important role in the sector. The category encompasses firms such as liner and port agencies, freight forwarders and shipbrokers, who link......, by its global character and by volatility. As such, the industry offers an interesting and generalizable environment for research. Moreover, the choice of the middleman, an intermediary in the value chain, as the object of study, offers additional insights into the complex industry and value chain...

  19. Hγ Line Spectrum of Intermediate Polars

    Directory of Open Access Journals (Sweden)

    Yonggi Kim

    1998-06-01

    Full Text Available Kim & Beuermann (1995, 1996 have developed a model for the propagation of X-rays from the accreting white dwarf through the infalling material and the re-emission of the energy deposited by photo-absorption in the optical (and UV spectral range. By using this model, we calculate the profiles of the Hγ emission-line spectrum of intermediate polars. Photoabsorption of X-rays by the infalling material is the dominant process in forming the observed energy-dependent rotational modulation of the X-ray flux. X-ray and optical modulations are sensitive to model parameters in different ways. In principle, these dependencies allow us to obtain improved insight into the accretion geometry of the intermediate polars. We present results of our calculations and compare them with the Hβ line spectrum (Kim & Beuermann 1996.

  20. Intermediate storage for the Start accelerator

    International Nuclear Information System (INIS)

    Gaponenko, N.I.; Tkach, Yu.V.; Stepanenko, I.A.; Kozachek, A.S.; Komarov, A.D.; Gadetskij, N.P.

    1988-01-01

    Usage of the chain of series-connected capacitors, placed near the voltage pulse generator (VPG) cascades, as an intermediate storage (IS) has allowed to reduce the inductance of the PG-IS charging circuit and to reduce storage charging time up to 30 ns. In such cases the electrical strength of the IS capacitor insulation is essentially higher, than at dc voltage, it has allowed to reduce the number of capacitors in the chain and to reduce IS self-inductance. Additional ways to reduce the inductance of the VPG-IS charging circuit are considered. Reduction of storage charging time has allowed to stabilize the operation of the commutator, which connects the intermediate storage with the accelerator shaping line

  1. Far from the intermediate nuclear field

    International Nuclear Information System (INIS)

    Dietrich, K.; Wagner, G.J.; Gregoire, C.; Campi, X.; Silvestre-Brac, B.; Platchkov, S.; Mayer, B.; Abgrall, Y.; Bohigas, O.; Grange, P.; Signarbieux, C.

    1988-01-01

    Pairing correlations in nuclear physics; the BCS state and quasi-particles; the layer model; collision effects on nuclear dynamics; the theory of cluster formation (application to nucleus fragmentation); short range correlations (few-particle systems); deuterium electron scattering; dibaryonic resonances; traditional and exotic hadron probes of nuclear structure; spectral fluctuations and chaotic motion; corrections to the intermediate nuclear field (nonrelativistic and other effects); and heavy nuclei splitting and nuclear superfluidity are introduced [fr

  2. International express student's book : pre-intermediate

    CERN Document Server

    Taylor, Liz

    1996-01-01

    The New Edition of International Express Pre-Intermediate retains all the keys features of this popular and successel four-level course. It combines engaging, up-to-date topics with a time-efficient and student-centred approach to language work, and clearly focused activities that reflect learner's real communicative needs - the ideal course for professional adults who use English for work, travel, and socializing.

  3. Assembly of intermediates for rapid membrane fusion.

    Science.gov (United States)

    Harner, Max; Wickner, William

    2018-01-26

    Membrane fusion is essential for intracellular protein sorting, cell growth, hormone secretion, and neurotransmission. Rapid membrane fusion requires tethering and Sec1-Munc18 (SM) function to catalyze R-, Qa-, Qb-, and Qc-SNARE complex assembly in trans , as well as SNARE engagement by the SNARE-binding chaperone Sec17/αSNAP. The hexameric vacuolar HOPS ( ho motypic fusion and vacuole p rotein s orting) complex in the yeast Saccharomyces cerevisiae tethers membranes through its affinities for the membrane Rab GTPase Ypt7. HOPS also has specific affinities for the vacuolar SNAREs and catalyzes SNARE complex assembly, but the order of their assembly into a 4-SNARE complex is unclear. We now report defined assembly intermediates on the path to membrane fusion. We found that a prefusion intermediate will assemble with HOPS and the R, Qa, and Qc SNAREs, and that this assembly undergoes rapid fusion upon addition of Qb and Sec17. HOPS-tethered membranes and all four vacuolar SNAREs formed a complex that underwent an even more dramatic burst of fusion upon Sec17p addition. These findings provide initial insights into an ordered fusion pathway consisting of the following intermediates and events: 1) Rab- and HOPS-tethered membranes, 2) a HOPS:R:Qa:Qc trans -complex, 3) a HOPS:4-SNARE trans -complex, 4) an engagement with Sec17, and 5) the rapid lipid rearrangements during fusion. In conclusion, our results indicate that the R:Qa:Qc complex forms in the context of membrane, Ypt7, HOPS, and trans -SNARE assembly and serves as a functional intermediate for rapid fusion after addition of the Qb-SNARE and Sec17 proteins. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. The Risk of Severe Hypoglycemia in Patients with Type 2 Diabetes Mellitus Starting Insulin Therapy with Premixed Insulin Analogues Taken Twice Daily: An Observational Study in Turkish Patients

    Directory of Open Access Journals (Sweden)

    Mustafa Sait Gönen

    2013-12-01

    Full Text Available Purpose: To assess the risk of severe hypoglycemia in Turkish patients with type 2 diabetes mellitus (T2DM starting insulin therapy with premixed insulin analogues alone or in combination with oral antihyperglycemic medications. Material and Method: Data from a subset of Turkish patients who participated in a 1-year, multinational, multicenter, prospective observational study were evaluated. Insulin treatment was initiated using commonly prescribed premixed regimens: insulin lispro mix 25 (25% insulin lispro, 75% insulin lispro protamine suspension or biphasic insulin aspart 30/70 (30% insulin aspart, 70% insulin aspart protamine suspension twice daily. Results: Of the 154 patients treated, 61 (39.6% were male with a mean age of 56 years and a T2DM duration of 8.9 years. Twelve patients (7.8% experienced ≥1 episode of severe hypoglycemia, but all recovered. The severe hypoglycemic rate was 0.14 episodes/patient-year. The mean glycated hemoglobin decreased by 2.7% (10.4% to 7.8% and fasting plasma glucose by 115.9 mg/dL (265.3 mg/dL to 157.6 mg/dL (p<0.0001. Self-monitored blood glucose (2-hour post morning meal decreased by 163.3 mg/dL (327.0 mg/dL to 216.2 mg/dL; p<0.0001. Self-monitored blood glucose level was low, particularly at the 2-hour post evening meal. Body mass index increased by 1.4 kg/m2, and total daily insulin dose by 4.2 IU. Discussion: In Turkish patients with T2DM, initiation of premixed insulin analogues during routine clinical care significantly improves glycemic control during the first year of treatment, but comes with a risk for severe hypoglycemia. Improvements in physician and patient education within the Turkish population regarding hypoglycemia management may be of benefit. Turk Jem 2013; 17: 83-8

  5. 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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    visits; as well as the glucose infusion rates required to keep glucose levels at target. During hypoglycemia, naltrexone, in comparison to the placebo group, induced an increase in epinephrine levels (P=0.05). However, no statistically significant differences in glucagon, cortisol, and growth hormone...... before the clamp study the participants received 100 mg of naltrexone or placebo orally. Counterregulatory hormonal responses were assessed at baseline and during each step of the hyperinsulinemic-clamp. RESULTS: Glucose and insulin levels did not differ significantly between the naltrexone and placebo...

  7. Permanent Neonatal Diabetes in a Patient with a KCNJ11/Q52R Mutation Accompanied by Intermittent Hypoglycemia and Liver Failure

    Directory of Open Access Journals (Sweden)

    Majzoub JosephA

    2009-09-01

    Full Text Available The most common monogenic cause of neonatal diabetes is mutation in KCNJ11, which encodes a potassium channel in pancreatic beta cells. Some mutations in this gene, including Q52R, have been described in association with neurological deficits, but never with hepatic involvement. We report the second case of neonatal diabetes in a patient with a KCNJ11 Q52R mutation. This patient's clinical course did not include obvious neurological deficits despite the presence of prematurity, but did include transient hyperbilirubinemia, and recurrent hypoglycemia. The phenotypic spectrum of KCNJ11 mutations is variable and is likely influenced by additional genetic and environmental factors.

  8. Severe hypoglycemia rates and associated costs among type 2 diabetics starting basal insulin therapy in the United States.

    Science.gov (United States)

    Ganz, Michael L; Wintfeld, Neil S; Li, Qian; Lee, Yuan-Chi; Gatt, Elyse; Huang, Joanna C

    2014-10-01

    To derive current real-world data on the rates and costs of severe hypoglycemia (SH) for people with type 2 diabetes mellitus (T2D) who have initiated basal insulin therapy and to examine differences in SH rates and costs stratified by history of prior SH events. We used a nation-wide electronic health records database that included encounter and laboratory data, as well as clinical notes, to estimate the rates and costs of SH events among adults with T2D who initiated basal insulin between 2008 and 2011. Unadjusted and regression-adjusted rates and quarterly costs were calculated for all patients as well as stratified by history of a SH event before starting basal insulin and history of a SH event during the basal insulin titration period. We identified 7235 incident cases of basal insulin use among patients with T2D who did not use insulin during the previous 12 months. Regression-adjusted incidence and total event rates were 10.36 and 11.21 per 100 patient-years, respectively. A history of SH events during the pre-index baseline and post-index titration periods were statistically significantly associated with both the incidence and total event rates (p history of previous SH or SH events during the titration period were not statistically significantly associated with costs. These results suggest that the real-world burden of SH is high among people with T2D who start using basal insulin and that history of previous SH events, both before starting insulin and during the insulin titration period, influences future SH. These results can also provide insights into interventions that can prevent or delay SH. These results should, however, be interpreted in light of the key limitations of our study: not all SH events may have been captured or coded in the database, data on filled prescriptions were not available, and the post-titration follow-up period could have been divided into time units other than quarters (3 month blocks) resulting in potentially different

  9. What Is Hypoglycemia?

    Science.gov (United States)

    ... adults unless the starvation is severe, as in anorexia . Poisoning or overdoses of some substances, such as ... will ask about the patient's medical history and diet, in particular about the timing of the symptoms, ...

  10. Hypoglycemia in Emergency Department

    Directory of Open Access Journals (Sweden)

    Yu-Jang Su

    2015-03-01

    Conclusions: When hypoglycemic patients present in the emergency department, physicians should pay attention to the presence of infection, malignancy, liver diseases (liver cirrhosis and biliary tract infection, and acute renal failure.

  11. Health-related quality of life and utility values associated to hypoglycemia in patients with type 1 diabetes mellitus treated in the Brazilian Public Health System: a multicenter study.

    Science.gov (United States)

    Bahia, Luciana; Kupfer, Rosane; Momesso, Denise; Cabral, Debora A P; Tschiedel, Balduino; Puñales, Marcia; Lavigne, Suzana; Façanha, Cristina F S; Forti, Adriana C; Mendes, Angela D N; Tura, Bernardo R

    2017-01-01

    Hypoglycemia is a critical and limiting factor of a good metabolic control and can adversely affect the quality of life of diabetic patients. The aim of the study was to evaluate the health-related quality of life and calculate utilities values associated with hypoglycemia in patients with type 1 diabetes mellitus (T1DM). A multicenter, cross-sectional and observational study with T1DM patients from reference centers of the Brazilian public health system was conducted in three cities. Demographic and clinical data were collected, besides details on the frequency and severity of hypoglycemia. Health-related quality of life was assessed using EQ-5D instrument and utility values generated. 221 patients (107 women, 114 men), aged 29.8 ± 11.6 and disease duration of 14.2 ± 9.1 years were included. Most patients (n = 214, 96.8%) reported at least one symptomatic hypoglycemia in the last three months, 68% (n = 150) reported nocturnal episodes and 34.8% (n = 77) reported severe episodes. High frequency (daily or weekly) was observed in 38.6 and 26% of those reporting nocturnal or severe hypoglycemia, respectively. The median visual analog scale was 70 [60-85] for all patients, with differences between those with and without severe hypoglycemia (70 [60-80] vs 80 [61-90]; p = 0.006) and those with high and low frequency (62.5 [50-72.25] vs 70 [60-80]; p = 0.007). The median utility values was 0.801 [0.756-1.000] for all patients, with difference between those with high and low frequency of severe episodes (0.737 [0.628-1.000] vs 0.801 [0.756-1.000]; p = 0.02). This study shows the high frequency of hypoglycemia in a sample of T1DM patients treated in three reference centers of the Brazilian public health system and the impact of severe episodes on health-related quality of life. Utility values were generated and can be used in economic analysis for treatments that could decrease hypoglycemia and consequently improve quality of life.

  12. One-stage correction of intermediate imperforate anus in males ...

    African Journals Online (AJOL)

    Background: This prospective study was designed to assess the safety, cost effectiveness, and advantages of performing posterior sagittal anorectoplasty without colostomy on males with intermediate imperforate anus. Method: Five consecutive males with intermediate imperforate anus were entered into the study.

  13. Intermediate Temperature Solid Oxide Fuel Cell Development

    Energy Technology Data Exchange (ETDEWEB)

    S. Elangovan; Scott Barnett; Sossina Haile

    2008-06-30

    Solid oxide fuel cells (SOFCs) are high efficiency energy conversion devices. Present materials set, using yttria stabilized zirconia (YSZ) electrolyte, limit the cell operating temperatures to 800 C or higher. It has become increasingly evident however that lowering the operating temperature would provide a more expeditious route to commercialization. The advantages of intermediate temperature (600 to 800 C) operation are related to both economic and materials issues. Lower operating temperature allows the use of low cost materials for the balance of plant and limits degradation arising from materials interactions. When the SOFC operating temperature is in the range of 600 to 700 C, it is also possible to partially reform hydrocarbon fuels within the stack providing additional system cost savings by reducing the air preheat heat-exchanger and blower size. The promise of Sr and Mg doped lanthanum gallate (LSGM) electrolyte materials, based on their high ionic conductivity and oxygen transference number at the intermediate temperature is well recognized. The focus of the present project was two-fold: (a) Identify a cell fabrication technique to achieve the benefits of lanthanum gallate material, and (b) Investigate alternative cathode materials that demonstrate low cathode polarization losses at the intermediate temperature. A porous matrix supported, thin film cell configuration was fabricated. The electrode material precursor was infiltrated into the porous matrix and the counter electrode was screen printed. Both anode and cathode infiltration produced high performance cells. Comparison of the two approaches showed that an infiltrated cathode cells may have advantages in high fuel utilization operations. Two new cathode materials were evaluated. Northwestern University investigated LSGM-ceria composite cathode while Caltech evaluated Ba-Sr-Co-Fe (BSCF) based pervoskite cathode. Both cathode materials showed lower polarization losses at temperatures as low as 600

  14. Intermediate temperature solid oxide fuel cells.

    Science.gov (United States)

    Brett, Daniel J L; Atkinson, Alan; Brandon, Nigel P; Skinner, Stephen J

    2008-08-01

    High temperature solid oxide fuel cells (SOFCs), typified by developers such as Siemens Westinghouse and Rolls-Royce, operate in the temperature region of 850-1000 degrees C. For such systems, very high efficiencies can be achieved from integration with gas turbines for large-scale stationary applications. However, high temperature operation means that the components of the stack need to be predominantly ceramic and high temperature metal alloys are needed for many balance-of-plant components. For smaller scale applications, where integration with a heat engine is not appropriate, there is a trend to move to lower temperatures of operation, into the so-called intermediate temperature (IT) range of 500-750 degrees C. This expands the choice of materials and stack geometries that can be used, offering reduced system cost and, in principle, reducing the corrosion rate of stack and system components. This review introduces the IT-SOFC and explains the advantages of operation in this temperature regime. The main advances made in materials chemistry that have made IT operation possible are described and some of the engineering issues and the new opportunities that reduced temperature operation affords are discussed. This tutorial review examines the advances being made in materials and engineering that are allowing solid oxide fuel cells to operate at lower temperature. The challenges and advantages of operating in the so-called 'intermediate temperature' range of 500-750 degrees C are discussed and the opportunities for applications not traditionally associated with solid oxide fuel cells are highlighted. This article serves as an introduction for scientists and engineers interested in intermediate temperature solid oxide fuel cells and the challenges and opportunities of reduced temperature operation.

  15. Intermediate Energy Activation File (IEAF-99)

    International Nuclear Information System (INIS)

    Korovin, Yu.; Konobeev, A.; Pereslavtsev, P.; Stankovskij, A.; Fischer, U.; Moellendorff, U. von

    1999-01-01

    Nuclear data library IEAF-99, elaborated to study processes of interactions of intermediate energy neutrons with materials in accelerator driven systems, is described. The library is intended for activation and transmutation studies for materials irradiated by neutrons. IEAF-99 contains evaluated neutron induced reaction cross sections at the energies 0-150 MeV for 665 stable and unstable nuclei from C to Po. Approximately 50,000 excitation functions are included in the library. The IEAF-99 data are written in the ENDF-6 format combining MF = 3,6 MT = 5 data recording. (author)

  16. Thermoelectric power generator with intermediate loop

    Science.gov (United States)

    Bell, Lon E; Crane, Douglas Todd

    2013-05-21

    A thermoelectric power generator is disclosed for use to generate electrical power from heat, typically waste heat. An intermediate heat transfer loop forms a part of the system to permit added control and adjustability in the system. This allows the thermoelectric power generator to more effectively and efficiently generate power in the face of dynamically varying temperatures and heat flux conditions, such as where the heat source is the exhaust of an automobile, or any other heat source with dynamic temperature and heat flux conditions.

  17. MHD oxidant intermediate temperature ceramic heater study

    Science.gov (United States)

    Carlson, A. W.; Chait, I. L.; Saari, D. P.; Marksberry, C. L.

    1981-09-01

    The use of three types of directly fired ceramic heaters for preheating oxygen enriched air to an intermediate temperature of 1144K was investigated. The three types of ceramic heaters are: (1) a fixed bed, periodic flow ceramic brick regenerative heater; (2) a ceramic pebble regenerative heater. The heater design, performance and operating characteristics under conditions in which the particulate matter is not solidified are evaluated. A comparison and overall evaluation of the three types of ceramic heaters and temperature range determination at which the particulate matter in the MHD exhaust gas is estimated to be a dry powder are presented.

  18. Intermediate Bandgap Solar Cells From Nanostructured Silicon

    Energy Technology Data Exchange (ETDEWEB)

    Black, Marcie [Bandgap Engineering, Lincoln, MA (United States)

    2014-10-30

    This project aimed to demonstrate increased electronic coupling in silicon nanostructures relative to bulk silicon for the purpose of making high efficiency intermediate bandgap solar cells using silicon. To this end, we formed nanowires with controlled crystallographic orientation, small diameter, <111> sidewall faceting, and passivated surfaces to modify the electronic band structure in silicon by breaking down the symmetry of the crystal lattice. We grew and tested these silicon nanowires with <110>-growth axes, which is an orientation that should produce the coupling enhancement.

  19. 40 CFR 721.983 - Sulfonyl azide intermediate (generic).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Sulfonyl azide intermediate (generic... Substances § 721.983 Sulfonyl azide intermediate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as sulfonyl azide intermediate...

  20. Surface Intermediate Zone of Submerged Turbulent Buoyant Jet in Current

    DEFF Research Database (Denmark)

    Chen, H. B.; Larsen, Torben

    1995-01-01

    This paper deals with the intermediate zone between the jet and plume stages of a submerged buoyant discharge from sea outfall in current. The stability criteria, plume width and height after the intermediate zone and the dilution within the intermediate region have been studied theoretically...

  1. Intermediate product selection and blending in the food processing industry

    DEFF Research Database (Denmark)

    Kilic, Onur A.; Akkerman, Renzo; van Donk, Dirk Pieter

    2013-01-01

    This study addresses a capacitated intermediate product selection and blending problem typical for two-stage production systems in the food processing industry. The problem involves the selection of a set of intermediates and end-product recipes characterising how those selected intermediates...

  2. 42 CFR 54.12 - Treatment of intermediate organizations.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Treatment of intermediate organizations. 54.12... intermediate organizations. If a nongovernmental organization (referred to here as an “intermediate organization”), acting under a contract or other agreement with the Federal Government or a State or local...

  3. 40 CFR 86.246-94 - Intermediate temperature testing.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Intermediate temperature testing. 86... New Medium-Duty Passenger Vehicles; Cold Temperature Test Procedures § 86.246-94 Intermediate temperature testing. (a) This section is applicable to tests which are conducted at an intermediate...

  4. Can Morphing Methods Predict Intermediate Structures?

    Science.gov (United States)

    Weiss, Dahlia R.; Levitt, Michael

    2009-01-01

    Movement is crucial to the biological function of many proteins, yet crystallographic structures of proteins can give us only a static snapshot. The protein dynamics that are important to biological function often happen on a timescale that is unattainable through detailed simulation methods such as molecular dynamics as they often involve crossing high-energy barriers. To address this coarse-grained motion, several methods have been implemented as web servers in which a set of coordinates is usually linearly interpolated from an initial crystallographic structure to a final crystallographic structure. We present a new morphing method that does not extrapolate linearly and can therefore go around high-energy barriers and which can produce different trajectories between the same two starting points. In this work, we evaluate our method and other established coarse-grained methods according to an objective measure: how close a coarse-grained dynamics method comes to a crystallographically determined intermediate structure when calculating a trajectory between the initial and final crystal protein structure. We test this with a set of five proteins with at least three crystallographically determined on-pathway high-resolution intermediate structures from the Protein Data Bank. For simple hinging motions involving a small conformational change, segmentation of the protein into two rigid sections outperforms other more computationally involved methods. However, large-scale conformational change is best addressed using a nonlinear approach and we suggest that there is merit in further developing such methods. PMID:18996395

  5. Intermediate heat exchanger project for Super Phenix

    International Nuclear Information System (INIS)

    Roumailhac, J.; Desir, D.

    1975-01-01

    The Super Phenix (1200 MWe) intermediate heat exchangers are derived directly from those of Phenix (250 MWe). The intermediate exchangers are housed in the reactor vessel annulus: as this annulus must be of the smallest volume possible, these IHX are required to work at a high specific rating. The exchange surface is calculated for nominal conditions. A range is then defined, consistent with the above requirements and throughout which the ratio between bundle thickness and bundle length remains acceptable. Experimental technics and calculations were used to determine the number of tube constraint systems required to keep the vibration amplitude within permissible limits. From a knowledge of this number, the pressure drop produced by the primary flow can be calculated. The bundle geometry is determined together with the design of the corresponding tube plates and the way in which these plates should be joined to the body of the IHX. The experience (technical and financial) acquired in the construction of Phenix is then used to optimize the design of the Super Phenix project. An approximate definition of the structure of the IHX is obtained by assuming a simplified load distribution in the calculations. More sophisticated calculations (e.g. finite element method) are then used to determine the behaviour of the different points of the IHX, under nominal and transient conditions

  6. The intermediate endpoint effect in logistic and probit regression

    Science.gov (United States)

    MacKinnon, DP; Lockwood, CM; Brown, CH; Wang, W; Hoffman, JM

    2010-01-01

    Background An intermediate endpoint is hypothesized to be in the middle of the causal sequence relating an independent variable to a dependent variable. The intermediate variable is also called a surrogate or mediating variable and the corresponding effect is called the mediated, surrogate endpoint, or intermediate endpoint effect. Clinical studies are often designed to change an intermediate or surrogate endpoint and through this intermediate change influence the ultimate endpoint. In many intermediate endpoint clinical studies the dependent variable is binary, and logistic or probit regression is used. Purpose The purpose of this study is to describe a limitation of a widely used approach to assessing intermediate endpoint effects and to propose an alternative method, based on products of coefficients, that yields more accurate results. Methods The intermediate endpoint model for a binary outcome is described for a true binary outcome and for a dichotomization of a latent continuous outcome. Plots of true values and a simulation study are used to evaluate the different methods. Results Distorted estimates of the intermediate endpoint effect and incorrect conclusions can result from the application of widely used methods to assess the intermediate endpoint effect. The same problem occurs for the proportion of an effect explained by an intermediate endpoint, which has been suggested as a useful measure for identifying intermediate endpoints. A solution to this problem is given based on the relationship between latent variable modeling and logistic or probit regression. Limitations More complicated intermediate variable models are not addressed in the study, although the methods described in the article can be extended to these more complicated models. Conclusions Researchers are encouraged to use an intermediate endpoint method based on the product of regression coefficients. A common method based on difference in coefficient methods can lead to distorted

  7. Dust Evolution in Intermediate Velocity Clouds

    Science.gov (United States)

    Pinheiro Gonçalves, D.; Martin, P. G.; Blagrave, K.; Miville-Deschenes, M. A.

    We search for evidence of dust evolution in high Galactic latitude regions by looking at variations in the emissivities of dust associated with different velocity clouds. In order to do so, we spatially correlate infrared IRAS/IRIS dust maps with HI column density maps derived from 21-cm radio observations with the GBT. Our findings show that intermediate velocity clouds (IVCs or halo clouds) have a higher 60µm/100µm and lower 12µm/100µm color ratio when compared to dust in local low-velocity gas. This suggests that large thermal dust grains are shattered into smaller ones (VSGs) and that there is a low relative abundance of PAHs in IVCs.

  8. Slab tears and intermediate-depth seismicity

    Science.gov (United States)

    Meighan, Hallie E.; ten Brink, Uri S.; Pulliam, Jay

    2013-01-01

    Active tectonic regions where plate boundaries transition from subduction to strike slip can take several forms, such as triple junctions, acute, and obtuse corners. Well-documented slab tears that are associated with high rates of intermediate-depth seismicity are considered here: Gibraltar arc, the southern and northern ends of the Lesser Antilles arc, and the northern end of Tonga trench. Seismicity at each of these locations occurs, at times, in the form of swarms or clusters, and various authors have proposed that each marks an active locus of tear propagation. The swarms and clusters start at the top of the slab below the asthenospheric wedge and extend 30–60 km vertically downward within the slab. We propose that these swarms and clusters are generated by fluid-related embrittlement of mantle rocks. Focal mechanisms of these swarms generally fit the shear motion that is thought to be associated with the tearing process.

  9. Intermediate normal metal layers in superconducting circuitry

    International Nuclear Information System (INIS)

    Sweeney, M.F.; Gershenson, M.; Fleming, D.L.; Barta, R.E.

    1987-01-01

    This patent describes a superconducting device comprising a first superconducting layer, a junction layer on the first superconducting layer, an insulating layer on the first superconducting layer, at least one superconducting area on the junction layer surrounded by the insulator layer, superconducting connector pad means disposed over the superconducting area, and superconducting wire means electrically connected to the superconducting connector pad means. The improvement comprising a first metal layer is disposed over the insulator layer and intermediate the superconducting area. The connector pad means and a second metal layer are disposed between the connector pad means and the superconductor wire means. The first metal layer covers the superconducting area and the first and second metal layers are sufficiently thin to allow quantum mechanical tunneling between the connector pad means and the superconducting area and the connector pad means and the superconducting wire means, respectively

  10. Modernisation of the intermediate physics laboratory

    Science.gov (United States)

    Kontro, Inkeri; Heino, Olga; Hendolin, Ilkka; Galambosi, Szabolcs

    2018-03-01

    The intermediate laboratory courses at the Department of Physics, University of Helsinki, were reformed using desired learning outcomes as the basis for design. The reformed laboratory courses consist of weekly workshops and small-group laboratory sessions. Many of the laboratory exercises are open-ended and have several possible ways of execution. They were designed around affordable devices, to allow for the purchase of multiple sets of laboratory equipment. This allowed students to work on the same problems simultaneously. Thus, it was possible to set learning goals which build on each other. Workshop sessions supported the course by letting the students solve problems related to conceptual and technical aspects of each laboratory exercise. The laboratory exercises progressed biweekly to allow for iterative problem solving. Students reached the learning goals well and the reform improved student experiences. Neither positive or negative changes in expert-like attitudes towards experimental physics (measured by E-CLASS questionnaire) were observed.

  11. Melting of metallic intermediate level waste

    International Nuclear Information System (INIS)

    Huutoniemi, Tommi; Larsson, Arne; Blank, Eva

    2013-08-01

    This report presents a feasibility study of a melting facility for core components and reactor internals. An overview is given of how such a facility for treatment of intermediate level waste might be designed, constructed and operated and highlights both the possibilities and challenges. A cost estimate and a risk analysis are presented in order to make a conclusion of the technical feasibility of such a facility. Based on the authors' experience in operating a low level waste melting facility, their conclusion is that without technical improvements such a facility is not feasible today. This is based on the cost of constructing and operating such a facility, in conjunction with the radiological risks associated with operation and the uncertain benefits to disposal and long term safety

  12. Environmental issues of an intermediate city

    International Nuclear Information System (INIS)

    Ahmad, N.

    2005-01-01

    Our urban centers present a unique dimension of environmental problems. They are at one and the same time, enormous consumers of natural resources and produces of waste and pollution. In this respect intermediate cities and small towns appear to be more vulnerable to natural catastrophes and ecological accidents caused by human factors. While in large cities there exist pressure groups which attain government attention for the solution of their problems and have well equipped municipalities. However, a vast majority of the population lives in rural areas and depends upon medium sized cities and towns for access to services. These cities and towns form the pivot of economic, social, cultural and political life for a large part of the population. Therefore, it deserves more attention than bigger ones. This paper explores local people perception about urban environmental problems exist in the city. Attempts are also made to shape and guide municipality efforts to overcome such problems with available resources. (author)

  13. q-Gamow states for intermediate energies

    Energy Technology Data Exchange (ETDEWEB)

    Plastino, A. [La Plata National University and Argentina' s National Research Council, (IFLP-CCT-CONICET)-C. C. 727, 1900 La Plata (Argentina); Rocca, M.C., E-mail: mariocarlosrocca@gmail.com [La Plata National University and Argentina' s National Research Council, (IFLP-CCT-CONICET)-C. C. 727, 1900 La Plata (Argentina); Ferri, G.L. [Fac. de C. Exactas, National University La Pampa, Peru y Uruguay, Santa Rosa, La Pampa (Argentina); Zamora, D.J. [La Plata National University and Argentina' s National Research Council, (IFLP-CCT-CONICET)-C. C. 727, 1900 La Plata (Argentina)

    2016-11-15

    In a recent paper Plastino and Rocca (2016) [18] we have demonstrated the possible existence of Tsallis' q-Gamow states. Now, accelerators' experimental evidence for Tsallis' distributions has been ascertained only at very high energies. Here, instead, we develop a different set of q-Gamow states for which the associated q-Breit–Wigner distribution could easily be found at intermediate energies, for which accelerators are available at many locations. In this context, it should be strongly emphasized Vignat and Plastino (2009) [2] that, empirically, one never exactly and unambiguously “detects” pure Gaussians, but rather q-Gaussians. A prediction is made via Eq. (3.4).

  14. Being back home after intermediate care

    DEFF Research Database (Denmark)

    Martinsen, Bente; Harder, Ingegerd; Norlyk, Annelise

    2015-01-01

    Older people may face many challenges and experience insecurity after discharge from hospital to home. To bridge the potential gap between general hospital and home, the concept ‘Intermediate Care’ (IC) was developed at the beginning of 2000. IC aims to safeguard older people from being discharged...... to their home before they have sufficiently recovered, but knowledge within this area is sparse. In particular the experience of older people is yet to be explored. The aim of this study was to explore older people’s experiences of being back home after a stay in an IC unit. Data were drawn from 12 interviews....... Transcripts were analysed using a phenomenological approach. The essential meaning of being back home after a stay in an IC unit was characterised by ‘uncertainty’. Four constituents emerged: ‘in a state of shock about coming home’, ‘dependence on informal helpers’, ‘a sense of isolation’, and ‘fear of losing...

  15. Turned Back: Mad Men as Intermedial Melodrama

    Directory of Open Access Journals (Sweden)

    Monique Rooney

    2012-09-01

    Full Text Available This essay draws on definitions of gesture (Giorgio Agamben and Peter Brooks and catachresis (Peter Brooks, Jacques Derrida to examine the primacy of non-verbal signifiers as communicators of meaning in AMC’s Mad Men. Beginning with an analysis of Mad Men’s credit sequence, it draws attention to Mad Men’s use of gesture and catachresis in relation to melodrama’s privileging of non-verbal and naturalistic expression and its persistence as an intermedial mode that has moved back and forth between various media (theatre, novel, cinema, television and now digital formats. It argues that Mad Men’s melodramatic aesthetic is one that obliquely, and via a gestural and rhetorical ‘turned back’, communicates its relation to the past and the present.

  16. Treatment of low and intermediate level wastes

    International Nuclear Information System (INIS)

    Hoehlein, G.

    1978-05-01

    The methods described of low and intermediate level waste treatment are based exclusively on operating experience gathered with the KfK facilities for waste management, the Karlsruhe Reprocessing Plant (WAK), the ALKEM fuel element fabrication plant, the MZFR, KNK and FR 2 reactors as well as at the Karlsruhe Nuclear Research Center and at the state collecting depot of Baden-Wuerttemberg. The processing capacities and technical status are similar to that in 1976. With an annual throughput of 10000 m 3 of solid and liquid raw wastes, an aggregate activity of 85000 Ci, 500 kg of U and 2 kg of Pu, final waste in the amount of 500 m 3 was produced which was stored in the ASSE II salt mine. (orig.) [de

  17. Fission cross section measurements at intermediate energies

    International Nuclear Information System (INIS)

    Laptev, Alexander

    2005-01-01

    The activity in intermediate energy particle induced fission cross-section measurements of Pu, U isotopes, minor actinides and sub-actinides in PNPI of Russia is reviewed. The neutron-induced fission cross-section measurements are under way in the wide energy range of incident neutrons from 0.5 MeV to 200 MeV at the GNEIS facility. In number of experiments at the GNEIS facility, the neutron-induced fission cross sections were obtained for many nuclei. In another group of experiments the proton-induced fission cross-section have been measured for proton energies ranging from 200 to 1000 MeV at 100 MeV intervals using the proton beam of PNPI synchrocyclotron. (author)

  18. Melting of metallic intermediate level waste

    Energy Technology Data Exchange (ETDEWEB)

    Huutoniemi, Tommi; Larsson, Arne; Blank, Eva [Studsvik Nuclear AB, Nykoeping (Sweden)

    2013-08-15

    This report presents a feasibility study of a melting facility for core components and reactor internals. An overview is given of how such a facility for treatment of intermediate level waste might be designed, constructed and operated and highlights both the possibilities and challenges. A cost estimate and a risk analysis are presented in order to make a conclusion of the technical feasibility of such a facility. Based on the authors' experience in operating a low level waste melting facility, their conclusion is that without technical improvements such a facility is not feasible today. This is based on the cost of constructing and operating such a facility, in conjunction with the radiological risks associated with operation and the uncertain benefits to disposal and long term safety.

  19. On the Intermediate Line Region in AGNs

    Directory of Open Access Journals (Sweden)

    Tek P. Adhikari

    2017-09-01

    Full Text Available In this paper we explore the intermediate line region (ILR by using the photoionisation simulations of the gas clouds present at different radial distances from the center, corresponding to the locations from BLR out to NLR in four types of AGNs. We let for the presence of dust whenever conditions allow for dust existence. All spectral shapes are taken from the recent multi-wavelength campaigns. The cloud density decreases with distance as a power law. We found that the slope of the power law density profile does not affect the line emissivity radial profiles of major emission lines: Hβ, He II, Mg II, C III, and O III. When the density of the cloud at the sublimation radius is as high as 1011.5 cm−3, the ILR should clearly be seen in the observations independently of the shape of the illuminating radiation. Moreover, our result is valid for low ionization nuclear emission regions of active galaxies.

  20. Intermediate storage device of start accelerator

    International Nuclear Information System (INIS)

    Gaponenko, N.I.; Tkach, Yu.V.; Stepanenko, I.A.; Kozachek, A.S.; Komarov, A.D.; Gadetskii, N.P.

    1989-01-01

    The use as an intermediate storage device (ISD) of a chain of series-connected capacitors near the stages of a voltage-pulse generator (VPG) reduces the inductance of the VPG-ISD charging circuit and reduces the charging time to 330 nsec. For such times, the electric strength of the capacitor insulation is considerably higher than for dc voltage, which makes it possible to reduce the number of capacitors in the chain and the inductance of the ISD. Additional methods for reduction of the inductance of the VPG-ISD charging circuit are examined. Reduction of the charging time of the storage device makes the operation of the switch connecting the ISD to the shaping line more stable

  1. Intermediate Ethanol Blends Catalyst Durability Program

    Energy Technology Data Exchange (ETDEWEB)

    West, Brian H; Sluder, Scott; Knoll, Keith; Orban, John; Feng, Jingyu

    2012-02-01

    In the summer of 2007, the U.S. Department of Energy (DOE) initiated a test program to evaluate the potential impacts of intermediate ethanol blends (also known as mid-level blends) on legacy vehicles and other engines. The purpose of the test program was to develop information important to assessing the viability of using intermediate blends as a contributor to meeting national goals for the use of renewable fuels. Through a wide range of experimental activities, DOE is evaluating the effects of E15 and E20 - gasoline blended with 15% and 20% ethanol - on tailpipe and evaporative emissions, catalyst and engine durability, vehicle driveability, engine operability, and vehicle and engine materials. This report provides the results of the catalyst durability study, a substantial part of the overall test program. Results from additional projects will be reported separately. The principal purpose of the catalyst durability study was to investigate the effects of adding up to 20% ethanol to gasoline on the durability of catalysts and other aspects of the emissions control systems of vehicles. Section 1 provides further information about the purpose and context of the study. Section 2 describes the experimental approach for the test program, including vehicle selection, aging and emissions test cycle, fuel selection, and data handling and analysis. Section 3 summarizes the effects of the ethanol blends on emissions and fuel economy of the test vehicles. Section 4 summarizes notable unscheduled maintenance and testing issues experienced during the program. The appendixes provide additional detail about the statistical models used in the analysis, detailed statistical analyses, and detailed vehicle specifications.

  2. Connectomic intermediate phenotypes for psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Alex eFornito

    2012-04-01

    Full Text Available Psychiatric disorders are phenotypically heterogeneous entities with a complex genetic basis. To mitigate this complexity, many investigators study so-called intermediate phenotypes that putatively provide a more direct index of the physiological effects of candidate genetic risk variants than overt psychiatric syndromes. Magnetic resonance imaging (MRI is a particularly popular technique for measuring such phenotypes because it allows interrogation of diverse aspects of brain structure and function in vivo. Much of this work however, has focused on relatively simple measures that quantify variations in the physiology or tissue integrity of specific brain regions in isolation, contradicting an emerging consensus that most major psychiatric disorders do not arise from isolated dysfunction in one or a few brain regions, but rather from disturbed interactions within and between distributed neural circuits; i.e., they are disorders of brain connectivity. The recent proliferation of new MRI techniques for comprehensively mapping the entire connectivity architecture of the brain, termed the human connectome, has provided a rich repertoire of tools for understanding how genetic variants implicated in mental disorder impact distinct neural circuits. In this article, we review research using these connectomic techniques to understand how genetic variation influences the connectivity and topology of human brain networks. We highlight recent evidence from twin and imaging genetics studies suggesting that the penetrance of candidate risk variants for mental illness, such as those in SLC6A4, MAOA, ZNF804A and APOE, may be higher for intermediate phenotypes characterised at the level of distributed neural systems than at the level of spatially localised brain regions. The findings indicate that imaging connectomics provides a powerful framework for understanding how genetic risk for psychiatric disease is expressed through altered structure and function of

  3. 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...

  4. 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.

  5. Replacing Insulin Glargine with Neutral Protamine Hagedorn (NPH) Insulin in a Subpopulation of Study Subjects in the Action to Control Cardiovascular Risk in Diabetes (ACCORD): Effects on Blood Glucose Levels, Hypoglycemia and Patient Satisfaction.

    Science.gov (United States)

    Berard, Lori; Cameron, Brett; Woo, Vincent; Stewart, John

    2015-08-01

    To ensure patient safety when replacing insulin glargine (IG) with neutral protamine Hagedorn (NPH) insulin and to determine differences in blood glucose control, frequency of hypoglycemia, insulin dosing, health resource utilization and quality of life between users of IG and NPH insulin. A single-site, open-label, randomized, 6-month comparative study of 66 patients from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Randomization was 1:1 to receive IG or NPH insulin. Data regarding blood glucose control, insulin dosage adjustment and recording of hypoglycemia episodes were obtained through telephone calls; office visits were conducted to measure weight, glycated hemoglobin, fasting plasma glucose and blood glucose profile. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was used to measure patients' satisfaction with their diabetes treatment. Rates of symptomatic hypoglycemia did not differ significantly between groups: 37.5±2.2 for the IG group and 31.1±2.1 for the NPH group. However, patients treated with NPH insulin had higher frequencies of severe hypoglycemia (6.1±0.9) compared with 2.7±0.6 for the IG group. A significant difference in changes in glycated hemoglobin (A1C) was observed between the groups: the mean ± standard error A1C decreases from baseline were -0.34%±0.11 for the IG group, vs -0.01%±0.10 for the NPH insulin group. The data obtained from the DTSQ showed greater treatment satisfaction in the IG group compared with the NPH insulin group. Switching from IG to NPH insulin resulted in more than double the rate of severe hypoglycemias and led to decreased metabolic control. Greater treatment satisfaction was observed with IG, compared with NPH insulin, as measured by change from baseline in the DTSQ scores. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  6. 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

    2018-03-02

    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.

  7. 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

  8. "Let the Algorithm Do the Work": Reduction of Hypoglycemia Using Sensor-Augmented Pump Therapy with Predictive Insulin Suspension (SmartGuard) in Pediatric Type 1 Diabetes Patients.

    Science.gov (United States)

    Biester, Torben; Kordonouri, Olga; Holder, Martin; Remus, Kerstin; Kieninger-Baum, Dorothee; Wadien, Tanja; Danne, Thomas

    2017-03-01

    A sensor-augmented insulin pump (SAP) using the MiniMed ® 640G system with SmartGuard™ technology allows an automatic stop of insulin delivery based on prediction of low glucose levels. Since pediatric patients are particularly prone to hypoglycemia, this device may offer additional protection beyond conventional sensor-augmented therapy. This prospective, pediatric multicenter user evaluation assessed 6 weeks of SAP with SmartGuard (threshold setting for hypoglycemia: 70 mg/dL) compared to a preceding period of 2 weeks with SAP only. The primary outcome was the potential reduction in the frequency of hypoglycemic episodes and hypoglycemic intensity (area under the curve [AUC] and time insulin pump use (average age: 11.6 ± 5.1 years, 15 female, average type 1 diabetes duration: 7.5 ± 4.2 years, mean ± SD) who had on average 3.2 ± 1.0 predictive suspensions/patient/day. The mean sensor glucose minimum during suspension was 78 ± 6 mg/dL and the average suspension time was 155 ± 47 min/day. Use of SmartGuard in patients treated as per the protocol (n = 18) reduced the number of instances in which the glucose level was insulin delivery followed by carbohydrate intake resulted in significantly higher glucose levels 1 h after suspension compared to SmartGuard suspensions with automatic resume (190.8 ± 26.5 vs. 138.7 ± 10.3 mg/dL; P insulin suspension technology, extra carbohydrate intake in response to an alarm combined with manual resumption is likely to cause rebound hyperglycemia. The best results were achieved when the user did not interfere with pump operation.

  9. Fetal intermediate lobe is stimulated by parturition.

    Science.gov (United States)

    Facchinetti, F; Lanzani, A; Genazzani, A R

    1989-11-01

    The fetal pituitary gland secretes beta-endorphin in blood in response to delivery. However, other forms of endorphin have recently been observed in the fetal pituitary, such as N-acetyl-beta-endorphin, which is devoid of opiate activity, and a desacetylated form of alpha-melanocyte-stimulating hormone. Both endorphins originate in the pituitary intermediate lobe. The sensitivity of this lobe to labor stress was assessed by the evaluation of beta-endorphin, N-acetyl-beta-endorphin, melanocyte-stimulating hormone, and desacetylated alpha-melanocyte-stimulating hormone in maternal plasma and cord blood in 11 cases of vaginal delivery and 10 cases of elective cesarean section without labor. Plasma peptide levels were determined by specific radioimmunoassays after extraction on Sep-Pak C-18 cartridges and high-performance liquid chromatography fractionation. Cord blood samples of infants delivered vaginally showed higher beta-endorphin (8.5 +/- 1.6 pmol/L, mean +/- SE) and desacetylated alpha-melanocyte-stimulating hormone (13.6 +/- 3.2 pmol/L) levels than those delivered by elective cesarean section (3.7 +/- 0.8 and 4.2 +/- 1.1 pmol/L, for beta-endorphin and desacetylated alpha-melanocyte-stimulating hormone, respectively). N-acetyl-beta-endorphin and alpha-melanocyte-stimulating hormone levels do not differ in relation to the mode of delivery. In maternal circulation beta-endorphin levels were higher in those delivered vaginally (5.2 pm 1) than in women who had cesarean sections (2.5 +/- 0.5 pmol/L), whereas no changes were found for the other peptides. In vaginal deliveries, the level of desacetylated alpha-melanocyte-stimulating hormone was higher in cord blood (13.6 +/- 3.2 pmol/L) than in maternal plasma (6.5 +/- 3 pmol/L); there were no significant differences with regard to the other peptides. Fetal and maternal levels of all the peptides were similar in cases of cesarean section. We conclude that parturition activates proopiomelanocortin peptide release from

  10. Taxation of Financial Intermediation Activities in Hong Kong

    OpenAIRE

    Jack M. Mintz; Stephen R. Richardson

    2001-01-01

    This paper discusses issues related to the taxation of financial intermediation in Hong Kong in the context of Hong Kong's position as a major regional financial centre. It first provides some background analysis as to the definition of financial intermediation and identification of the providers of financial services. This is then followed by a discussion of the principles of taxation applicable to financial intermediation, including a comparison of income taxes to consumption taxes. Some sp...

  11. Intermediate mass fragments emission in binary fragmentation model

    International Nuclear Information System (INIS)

    Bhattacharya, C.; Bhattacharya, S.

    1991-01-01

    Intermediate mass fragments emission in intermediate-energy nucleus-nucleus collisions has been studied in the framework of a generalized model where the fragments are assumed to be emitted from binary fissionlike decay of the fully equilibrated compound nucleus. The present formulation, with a schematic exit channel shape configuration and simple rotating liquid-drop nuclear potential, has been found to explain most of the intermediate mass fragments emission cross sections reasonably well without incorporating any free parameters in the calculation

  12. La escritura intermedial en la escena actual

    Directory of Open Access Journals (Sweden)

    Luis Thenon

    2013-08-01

    Full Text Available Las escrituras artísticas actuales integran, en el marco determinado por las realidades intermediales de la escena tecnológica, el concepto de diseño como manipulación perceptiva del espacio, lo que constituye uno de los instrumentos determinantes en la puesta en marcha de un cuadro compositivo de resonancias transformacionales. Podríamos en este sentido hablar de una nueva ecología artística y en especial, teatral. En la renovación del pensamiento teatral actualizado, fuertemente influenciado por la estructura discursiva cinematográfica y por los universos sensoriales de la cultura tecnológica de la imagen y del sonido, está la base de la multiplicación diegética, de la superposición, de la fragmentación de los discursos y de la praxis inter-relacional en la que radica, en gran medida, la potencia intermedial de la escena actual.

  13. Electron scattering from sodium at intermediate energies

    International Nuclear Information System (INIS)

    Mitroy, J.; McCarthy, I.E.

    1986-10-01

    A comprehensive comparison is made between theoretical calculations and experimental data for intermediate energy (≥ 10 eV) electron scattering from sodium vapour. The theoretical predictions of coupled-channels calculations (including one, two or four channels) do not agree with experimental values of the differential cross sections for elastic scattering or the resonant 3s to 3p excitation. Increasingly-more-sophisticated calculations, incorporating electron correlations in the target states, and also including core-excited states in the close-coupling expansion, are done at a few selected energies in an attempt to isolate the cause of the discrepancies between theory and experiment. It is found that these more-sophisticated calculations give essentially the same results as the two- and four-channel calculations using Hartree-Fock wavefunctions. Comparison of the sodium high-energy elastic differential cross sections with those of neon suggests that the sodium differential cross section experiments may suffer from systematic errors. There is also disagreement, at the higher energies, between theoretical values for the scattering parameters and those that are derived from laser-excited superelastic scattering and electron photon coincidence experiments. When allowance is made for the finite acceptance angle of the electron spectrometers used in the experiments by convoluting the theory with a function representing the distribution of electrons entering the electron spectrometer it is found that the magnitudes of the differences between theory and experiment are reduced

  14. On the Intermediate Line Region in AGNs

    Energy Technology Data Exchange (ETDEWEB)

    Adhikari, Tek P.; Różańska, Agata; Hryniewicz, Krzysztof [Nicolaus Copernicus Astronomical Center, Polish Academy of Sciences, Warsaw (Poland); Czerny, Bozena [Nicolaus Copernicus Astronomical Center, Polish Academy of Sciences, Warsaw (Poland); Center for Theoretical Physics, Polish Academy of Sciences, Warsaw (Poland); Ferland, Gary J., E-mail: tek@camk.edu.pl [Department of Physics and Astronomy, The University of Kentucky, Lexington, KY (United States)

    2017-09-29

    In this paper we explore the intermediate line region (ILR) by using the photoionisation simulations of the gas clouds present at different radial distances from the center, corresponding to the locations from BLR out to NLR in four types of AGNs. We let for the presence of dust whenever conditions allow for dust existence. All spectral shapes are taken from the recent multi-wavelength campaigns. The cloud density decreases with distance as a power law. We found that the slope of the power law density profile does not affect the line emissivity radial profiles of major emission lines: Hβ, He II, Mg II, C III, and O III. When the density of the cloud at the sublimation radius is as high as 10{sup 11.5} cm{sup −3}, the ILR should clearly be seen in the observations independently of the shape of the illuminating radiation. Moreover, our result is valid for low ionization nuclear emission regions of active galaxies.

  15. Substrate radical intermediates in soluble methane monooxygenase

    International Nuclear Information System (INIS)

    Liu Aimin; Jin Yi; Zhang Jingyan; Brazeau, Brian J.; Lipscomb, John D.

    2005-01-01

    EPR spin-trapping experiments were carried out using the three-component soluble methane monooxygenase (MMO). Spin-traps 5,5-dimethyl-1-pyrroline N-oxide (DMPO), α-4-pyridyl-1-oxide N-tert-butylnitrone (POBN), and nitrosobenzene (NOB) were used to investigate the possible formation of substrate radical intermediates during catalysis. In contrast to a previous report, the NADH-coupled oxidations of various substrates did not produce any trapped radical species when DMPO or POBN was present. However, radicals were detected by these traps when only the MMO reductase component and NADH were present. DMPO and POBN were found to be weak inhibitors of the MMO reaction. In contrast, NOB is a strong inhibitor for the MMO-catalyzed nitrobenzene oxidation reaction. When NOB was used as a spin-trap in the complete MMO system with or without substrate, EPR signals from an NOB radical were detected. We propose that a molecule of NOB acts simultaneously as a substrate and a spin-trap for MMO, yielding the long-lived radical and supporting a stepwise mechanism for MMO

  16. Uranium concentration monitor manual, secondary intermediate evaporator

    International Nuclear Information System (INIS)

    Russo, P.A.; Sprinkle, J.K. Jr.; Slice, R.W.; Strittmatter, R.B.

    1985-08-01

    This manual describes the design, operation, and measurement control procedures for the automated uranium concentration monitor on the secondary intermediate evaporator at the Oak Ridge Y-12 Plant. The nonintrusive monitor provides a near-real time readout of uranium concentration in the return loop of time recirculating evaporator for purposes of process monitoring and control. A detector installed near the bottom of the return loop is used to acquire spectra of gamma rays from the evaporator solutions during operation. Pulse height analysis of each spectrum gives the information required to deduce the concentration of uranium in the evaporator solution in near-real time. The visual readout of concentration is updated at the end of every assay cycle. The readout includes an alphanumeric display of uranium concentration and an illuminated, colored LED (in an array of colored LEDs) indicating whether the measured concentration is within (or above or below) the desired range. An alphanumeric display of evaporator solution acid molarity is also available to the operator. 9 refs., 16 figs., 4 tabs

  17. Intermediate Temperature Fluids Life Tests — Theory

    Science.gov (United States)

    Tarau, Calin; Sarraf, David B.; Locci, Ivan E.; Anderson, William G.

    2007-01-01

    There are a number of different applications that could use heat pipes or loop heat pipes (LHPs) in the intermediate temperature range of 450 to 750 K, including space nuclear power system radiators, and high temperature electronics cooling. Potential working fluids include organic fluids, elements, and halides, with halides being the least understood, with only a few life tests conducted. Potential envelope materials for halide working fluids include pure aluminum, aluminum alloys, commercially pure (CP) titanium, titanium alloys, and corrosion resistant superalloys. Life tests were conducted with three halides (AlBr3, SbBr3, and TiCl4) and water in three different envelopes: two aluminum alloys (Al-5052, Al-6061) and CP-2 titanium. The AlBr3 attacked the grain boundaries in the aluminum envelopes, and formed TiAl compounds in the titanium. The SbBr3 was incompatible with the only envelope material that it was tested with, Al-6061. TiCl4 and water were both compatible with CP2-titanium. A theoretical model was developed that uses electromotive force differences to predict the compatibility of halide working fluids with envelope materials. This theory predicts that iron, nickel, and molybdenum are good envelope materials, while aluminum and titanium halides are good working fluids. The model is in good agreement with results from previous life tests, as well as the current life tests.

  18. Intermediate Temperature Fluids Life Tests - Theory

    Science.gov (United States)

    Tarau, Calin; Sarraf, David B.; Locci, Ivan E.; Anderson, William G.

    2008-01-01

    There are a number of different applications that could use heat pipes or loop heat pipes (LHPs) in the intermediate temperature range of 450 to 750 K, including space nuclear power system radiators, and high temperature electronics cooling. Potential working fluids include organic fluids, elements, and halides, with halides being the least understood, with only a few life tests conducted. Potential envelope materials for halide working fluids include pure aluminum, aluminum alloys, commercially pure (CP) titanium, titanium alloys, and corrosion resistant superalloys. Life tests were conducted with three halides (AlBr3, SbBr3, and TiCl4) and water in three different envelopes: two aluminum alloys (Al-5052, Al-6061) and Cp-2 titanium. The AlBr3 attacked the grain boundaries in the aluminum envelopes, and formed TiAl compounds in the titanium. The SbBr3 was incompatible with the only envelope material that it was tested with, Al-6061. TiCl4 and water were both compatible with CP2-titanium. A theoretical model was developed that uses electromotive force differences to predict the compatibility of halide working fluids with envelope materials. This theory predicts that iron, nickel, and molybdenum are good envelope materials, while aluminum and titanium halides are good working fluids. The model is in good agreement with results form previous life tests, as well as the current life tests.

  19. [Intermediate/high energy nuclear physics

    International Nuclear Information System (INIS)

    1989-01-01

    We have continued to develop a theoretical framework for the quark and gluon structure of nuclei. Our approach features a successful phenomenological model, the quark cluster model (QCM), and an ambitious program in the non-perturbative solution of quantum field theories. The effort in quantum field theory provides theoretical results to test or replace assumed ingredients of the QCM. By the explicit example of a scalar field theory in 2D we have solved the long-standing problem of how to treat the dynamics of the vacuum in light-front quantization. We now propose to solve the same problem for simple Fermion field theories in 2D such as the Gross-Neveu model. We propose in subsequent years to address QCD in low dimensionality with the purpose of extracting non-perturbative predictions for quark and gluon amplitudes in few baryon systems. Simultaneously with this new effort we will continue to develop extensions and applications of the QCM. We propose to continue predicting phenomena to be observed in high energy particle-nucleus collisions that reflect the rearrangement of quarks and gluons in nuclei. We have completed our analysis of the SLAC E101 and E133 experiments on Deuterium to elucidate the degree to which a six-quark cluster contribution is admissable in the Bjorken x > 1 data. We have completed our development of a parameterized thermal liquid drop model for light nuclei. In addition we have completed a set of predictions for the formation of a ''nuclear stratosphere'' in nuclei created by intermediate energy heavy ion interactions. These results motivate a new investigation of the temperature dependence of the ion-ion potential with particular emphasis on the thermal dependence of the barrier height and radius. We have also shown that a consistent treatment of relativistic effects is important for a theoretical description of the elastic magnetic form factor of 17 O. 85 refs

  20. Intermediate Syndrome Following Organophosphate Insecticide Poisoning

    Directory of Open Access Journals (Sweden)

    Chen-Chang Yang

    2007-11-01

    Full Text Available Acute organophosphate insecticide poisoning can manifest 3 different phases of toxic effects, namely, acute cholinergic crisis, intermediate syndrome (IMS, and delayed neuropathy. Among them, IMS has been considered as a major contributing factor of organophosphate-related morbidity and mortality because of its frequent occurrence and probable consequence of respiratory failure. Despite a high incidence, the pathophysiology that underlies IMS remains unclear. Previously proposed mechanisms of IMS include different susceptibility of various cholinergic receptors, muscle necrosis, prolonged acetylcholinesterase inhibition, inadequate oxime therapy, downregulation or desensitization of postsynaptic acetylcholine receptors, failure of postsynaptic acetylcholine release, and oxidative stress-related myopathy. The clinical manifestations of IMS typically occur within 24 to 96 hours, affecting conscious patients without cholinergic signs, and involve the muscles of respiration, proximal limb muscles, neck flexors, and muscles innervated by motor cranial nerves. With appropriate therapy that commonly includes artificial respiration, complete recovery develops 5–18 days later. Patients with atypical manifestations of IMS, especially a relapse or a continuum of acute cholinergic crisis, however, were frequently reported in clinical studies of IMS. The treatment of IMS is mainly supportive. Nevertheless, because IMS generally concurs with severe organophosphate toxicity and persistent inhibition of acetylcholinesterase, early aggressive decontamination, appropriate antidotal therapy, and prompt institution of ventilatory support should be helpful in ameliorating the magnitude and/or the incidence of IMS. Although IMS is well recognized as a disorder of neuromuscular junctions, its exact etiology, incidence, and risk factors are not clearly defined because existing studies are largely small-scale case series and do not employ a consistent and rigorous

  1. Intermediate frequency magnetic field and chick embryotoxicity.

    Science.gov (United States)

    Nishimura, Izumi; Tanaka, Keiko; Negishi, Tadashi

    2013-09-01

    Intermediate frequency magnetic fields (MFs) have widely been used in industrial machines and home appliances, such as induction heating cookers, although toxicity studies to evaluate the potential health risks of such fields are insufficient. In induction heating cookers, the MF source (i.e. hobs), is located near the abdominal position of a person cooking. Hence, developmental effects on the fetus may be a concern in case the person is a pregnant woman. Fertile White Leghorn eggs (60/group) were either exposed to 20 kHz, 1.1 mT(rms) or 60 kHz, 0.11 mT(rms) sinusoidal MFs for 19 days during embryogenesis. The same number of eggs served as a control group. In addition, a sham-sham experiment was conducted to validate the equality between exposure and control facilities. After exposure, embryos were examined for mortality rate and stage. Live embryos were evaluated for developmental stage and gross and skeletal anomalies. Length of upper beak and leg digits was also measured. Examinations were conducted in a blinded fashion to ensure quality assurance; experiments were triplicated for each frequency to confirm the outcome reproducibility. Mortality rate and stage, incidence of malformed embryos, and developmental variables in live embryos were found to be similar between the MF-exposed and corresponding control group. Incidence of gross anomalies such as mandibular edema and skeletal anomalies such as coccyx defects were low across the experiments, and no significant group differences were noted. In conclusion, exposure to 20 kHz or 60 kHz MF did not produce any significant teratogenic developmental effects in chick embryos. © 2013 The Authors. Congenital Anomalies © 2013 Japanese Teratology Society.

  2. Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes: a randomized clinical trial.

    Science.gov (United States)

    Ly, Trang T; Nicholas, Jennifer A; Retterath, Adam; Lim, Ee Mun; Davis, Elizabeth A; Jones, Timothy W

    2013-09-25

    Hypoglycemia is a critical obstacle to the care of patients with type 1 diabetes. Sensor-augmented insulin pump with automated low-glucose insulin suspension has the potential to reduce the incidence of major hypoglycemic events. To determine the incidence of severe and moderate hypoglycemia with sensor-augmented pump with low-glucose suspension compared with standard insulin pump therapy. A randomized clinical trial involving 95 patients with type 1 diabetes, recruited from December 2009 to January 2012 in Australia. Patients were randomized to insulin pump only or automated insulin suspension for 6 months. The primary outcome was the combined incidence of severe (hypoglycemic seizure or coma) and moderate hypoglycemia (an event requiring assistance for treatment). In a subgroup, counterregulatory hormone responses to hypoglycemia were assessed using the hypoglycemic clamp technique. Of the 95 patients randomized, 49 were assigned to the standard-pump (pump-only) therapy and 46 to the low-glucose suspension group. The mean (SD) age was 18.6 (11.8) years; duration of diabetes, 11.0 (8.9) years; and duration of pump therapy, 4.1 (3.4) years. The baseline rate of severe and moderate hypoglycemic events in the pump-only group was 20.7 vs 129.6 events per 100 patient months in the low-glucose suspension group. After 6 months of treatment, the event rates decreased from 28 to 16 in the pump-only group vs 175 to 35 in the low-glucose suspension group. The adjusted incidence rate per 100 patient-months was 34.2 (95% CI, 22.0-53.3) for the pump-only group vs 9.5 (95% CI, 5.2-17.4) for the low-glucose suspension group. The incidence rate ratio was 3.6 (95% CI, 1.7-7.5; P pump-only group vs mean, 7.6 (95%, CI, 7.4-7.9) to 7.5 (95% CI, 7.3-7.7) in the low-glucose suspension group. Counterregulatory hormone responses to hypoglycemia were not changed. There were no episodes of diabetic ketoacidosis or hyperglycemia with ketosis. Sensor-augmented pump therapy with automated

  3. Unification of favourable intermediate-, unfavourable intermediate-, and very high-risk stratification criteria for prostate cancer.

    Science.gov (United States)

    Zumsteg, Zachary S; Zelefsky, Michael J; Woo, Kaitlin M; Spratt, Daniel E; Kollmeier, Marisa A; McBride, Sean; Pei, Xin; Sandler, Howard M; Zhang, Zhigang

    2017-11-01

    To improve on the existing risk-stratification systems for prostate cancer. This was a retrospective investigation including 2 248 patients undergoing dose-escalated external beam radiotherapy (EBRT) at a single institution. We separated National Comprehensive Cancer Network (NCCN) intermediate-risk prostate cancer into 'favourable' and 'unfavourable' groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), and number of NCCN intermediate-risk factors. Similarly, NCCN high-risk prostate cancer was stratified into 'standard' and 'very high-risk' groups based on primary Gleason pattern, PPBC, number of NCCN high-risk factors, and stage T3b-T4 disease. Patients with unfavourable-intermediate-risk (UIR) prostate cancer had significantly inferior prostate-specific antigen relapse-free survival (PSA-RFS, P prostate cancer-specific mortality (PCSM, P prostate cancer. Similarly, patients with very high-risk (VHR) prostate cancer had significantly worse PSA-RFS (P prostate cancer. Moreover, patients with FIR and low-risk prostate cancer had similar outcomes, as did patients with UIR and SHR prostate cancer. Consequently, we propose the following risk-stratification system: Group 1, low risk and FIR; Group 2, UIR and SHR; and Group 3, VHR. These groups have markedly different outcomes, with 8-year distant metastasis rates of 3%, 9%, and 29% (P < 0.001) for Groups 1, 2, and 3, respectively, and 8-year PCSM of 1%, 4%, and 13% (P < 0.001) after EBRT. This modified stratification system was significantly more accurate than the three-tiered NCCN system currently in clinical use for all outcomes. Modifying the NCCN risk-stratification system to group FIR with low-risk patients and UIR with SHR patients, results in modestly improved prediction of outcomes, potentially allowing better personalisation of therapeutic recommendations. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  4. Borderline Personality Disorder in an Intermediate Psychological Therapies Service

    Science.gov (United States)

    Ryan, Seamus; Danquah, Adam N.; Berry, Katherine; Hopper, Mary

    2017-01-01

    The intermediate psychological therapies service is provided for individuals referred with common mental health problems within the primary care psychological therapies service, but whose difficulties are longstanding and/or complex. The prevalence of borderline personality disorder (BPD) in intermediate psychological therapy services has not been…

  5. Unfolding intermediates of the mutant His-107-Tyr of human ...

    Indian Academy of Sciences (India)

    When projected along a reaction coordinate these trajectories yield four distinguishable sets of structures that map qualitatively to folding intermediates of this mutant postulated earlier from experiments.We present in this article a detailed analysis of representative structures and proton transfer activity of these intermediates.

  6. "Affective Encounters": Live Intermedial Spaces in Sites of Trauma

    Science.gov (United States)

    Scott, Jo

    2016-01-01

    This article addresses live intermediality as a tool for creative learning in the context of workshops carried out with young people in the town of Terezin, in the Czech Republic, site of the Nazi concentration camp, Theresienstadt. Live intermediality, as a mode of live media practice, involves the real time mixing and merging of sound, image,…

  7. The management of intermediate level wastes in Sweden

    International Nuclear Information System (INIS)

    Hultgren, Aa.; Thegerstroem, C.

    1980-01-01

    A brief overview of current practices and research in Sweden on the management of intermediate level wastes is given. Intermediate level wastes include spent resins, filters and core components from the six power reactors in operation; radioactive wastes from nuclear fuel development at Studsvik and from non-nuclear applications are a minor contribution. (Auth.)

  8. 42 CFR 54a.12 - Treatment of intermediate organizations.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Treatment of intermediate organizations. 54a.12... CHARITABLE CHOICE REGULATIONS APPLICABLE TO STATES, LOCAL GOVERNMENTS AND RELIGIOUS ORGANIZATIONS RECEIVING... ABUSE PREVENTION AND TREATMENT SERVICES § 54a.12 Treatment of intermediate organizations. If a...

  9. Surface Intermediates on Metal Electrodes at High Temperature

    DEFF Research Database (Denmark)

    Zachau-Christiansen, Birgit; Jacobsen, Torben; Bay, Lasse

    1997-01-01

    The mechanisms widely suggested for the O2-reduc-tion or H2-oxidation SOFC reactions involve inter-mediate O/H species adsorbed on the electrode surface. The presence of these intermediates is investigated by linear sweep voltammetry. In airat moderate temperatures (500øC) Pt in contact with YSZ...

  10. Superlattice Intermediate Band Solar Cell on Gallium Arsenide

    Science.gov (United States)

    2015-02-09

    AFRL-RV-PS- AFRL-RV-PS- TR-2015-0048 TR-2015-0048 SUPERLATTICE INTERMEDIATE BAND SOLAR CELL ON GALLIUM ARSENIDE Alexandre Freundlich...SUBTITLE 5a. CONTRACT NUMBER FA9453-13-1-0232 Superlattice Intermediate Band Solar Cell on Gallium Arsenide 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER

  11. 21 CFR 312.315 - Intermediate-size patient populations.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Intermediate-size patient populations. 312.315... for Treatment Use § 312.315 Intermediate-size patient populations. Under this section, FDA may permit an investigational drug to be used for the treatment of a patient population smaller than that...

  12. Nuclear structure at intermediate energies. Progress report

    International Nuclear Information System (INIS)

    Bonner, B.E.; Mutchler, G.S.

    1992-01-01

    We report here oil the progress that we made for the nine months beginning October 1, 1991 for DOE Grant No. DE-FG05-87ER40309. The report covers the third year of a three year grant. Since we are submitting an accompanying Grant Renewal Proposal, we provide in this report more background information than usual for the different projects. The theme that unites the experiments undertaken by the Bonner Lab Medium Energy Group is a determination to understand in detail the many facets and manifestations of the strong interaction, that which is now referred to as nonperturbative QCD. Whether we are investigating the question of just what does carry the spin of baryons, or the extent of the validity of the SU(6) wavefunctions for the excited hyperons (as will be measured in our CEBAF experiment), or questions associated with the formation of a new state of matter predicted by QCD (the subject of AGS bar p experiment E854, AGS heavy ion experiment E810, as-well as the approved STAR experiment at RHIC), - all these projects share this common goal. FNAL E683 may well open a new field of investigation in nuclear physics: That of just how colored quarks and gluons interact with nuclear matter as they traverse nuclei of different-sizes. In most all of the experiments mentioned, above, the Bonner Lab Group is playing major leadership roles as well as doing a big fraction of the hard work that such experiments require. We use many of the facilities that are available to the intermediate energy physics community and we use our expertise to design and fabricate the detectors and instrumentation that are required to perform the measurements which we decide to do. The format we follow in the Progress Report is,to provide a concise, but fairly complete write-up on each project. The publications listed in Section In give much greater detail on many of the projects. The aim in this report is to focus on the physics goals, the results, and their significance

  13. 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

    Directory of Open Access Journals (Sweden)

    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

  14. Researchers Resolve Intermediate Mass Black Hole Mystery

    Science.gov (United States)

    2004-04-01

    New research, funded by the Royal Netherlands Academy of Sciences, the Institute of Advanced Physical and Chemical Research, NASA and the University of Tokyo, solved the mystery of how a black hole, with the mass more than several hundreds times larger than that of our Sun, could be formed in the nearby starburst galaxy, M82. Recent observations of the Chandra X-ray observatory (Matsumoto et al., 2001 ApJ 547, L25) indicate the presence of an unusually bright source in the star cluster MGG11 in the starburst galaxy M82. The properties of the X-ray source are best explained by a black hole with a mass of about a thousand times the mass of the Sun, placing it intermediate between the relatively small (stellar mass) black holes in the Milky way Galaxy and the supermassive black holes found in the nuclei of galaxies. For comparison, stellar-mass black holes are only a few times more massive than the Sun, whereas the black hole in the center of the Milky-way Galaxy is more than a few million times more massive than the Sun. An international team of researchers, using the world's fastest computer, the GRAPE-6 system in Japan, were engaged in a series of simulations of star clusters that resembled MGG11. They used the GRAPE-6 to perform simulations with two independently developed computer programs (Starlab and NBODY4 developed by Sverre Aarseth in Cambridge), both of which give the same qualitative result. The simulations ware initiated by high resolution observations of the star cluster MGG11 by McCrady et al (2003, ApJ 596, 240) using the Hubble Space Telescope and Keck, and by Harashima et al (2001) using the giant Subaru telescope. M82 Chandra X-ray image of the central region of the starburst galaxy M82. The GRAPE's detailed, star-by-star simulations represent the state of the art in cluster modeling. For the first time using the GRAPE, researchers perform simulations of the evolution of young and dense star clusters with up to 600000 stars; they calculate the

  15. Evaluation of FreeStyle Libre Flash Glucose Monitoring System on Glycemic Control, Health-Related Quality of Life, and Fear of Hypoglycemia in Patients with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Ayman A Al Hayek

    2017-12-01

    Full Text Available Background/objectives: In the current era of modern technology and the development of smart devices such as the flash glucose monitoring (FGM systems, patients can easily monitor their glucose levels more frequently without any inconvenience. In this study, we evaluate the effect of FreeStyle Libre FGM system on glycemic control, hypoglycemia, health-related quality of life (QoL, and the fear of hypoglycemia (FOH among children and young people with type 1 diabetes (T1D. Design and methods: A prospective study was conducted at the Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia, between January 2017 and May 2017 on 47 (aged 13-19 years registered patients with T1D who used conventional finger-pricking method for self-testing the glucose. At baseline visit, the FGM sensors were placed on each participant by a trained diabetes educator. The data collected from the sensors were computed to generate the respective ambulatory glucose profiles so as to determine the total number of scans conducted during the study period. At the baseline and at 3 months of the experiment, a trained interviewer administered the questionnaire Hypoglycemia Fear Survey-Child Version (HFS-C and PedsQL 3.0 (QoL questionnaire to each patient. The age, sex, weight, height, adjusted body mass index, duration of diabetes, treatment modality, and glycosylated hemoglobin A 1c (HbA 1c levels of each patient were recorded. Results: As compared with the baseline, a significant improvement was noted in the behavior of FOH ( P = .0001, worry ( P = .0001, QoL ( P = .002, HbA 1c level ( P = .008, and hypoglycemia ( P = .023 at 3 months. Significant improvement was noted in the behavior ( P = .0001, worry ( P = .0001, QoL ( P = .003, HbA 1c level ( P = .014, and hypoglycemia ( P = .001 among the multiple-dose insulin injection–treated patients as compared with baseline. Significant improvement was noted in the behavior ( P = .0001, worry ( P = .0001

  16. 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

    DEFF Research Database (Denmark)

    Geelhoed-Duijvestijn, Petronella H; Pedersen-Bjergaard, Ulrik; Weitgasser, Raimund

    2013-01-01

    be interpreted with caution because of different definitions of hypoglycemia severity, duration of the studies, and methods of data collection. Conclusions: NSHE were associated with use of extra healthcare resources and work-time loss in all countries studied, suggesting that NSHE have considerable impact...... 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. Limitations: Direct comparisons between studies must...

  17. Language in use intermediate : self-study workbook

    CERN Document Server

    Doff, Adrian

    1994-01-01

    Each of the four levels comprises about 80 hours of class work, with additional time for the self-study work. The Teacher's Book contains all the pages from the Classroom Book, with interleaved teaching notes including optional activities to cater for different abilities. There is a video to accompany the Beginner, Pre-intermediate and Intermediate levels. Each video contains eight stimulating and entertaining short programmes, as well as a booklet of photocopiable activities. Free test material is available in booklet and web format for Beginner and Pre-intermediate levels. Visit www.cambridge.org/elt/liu or contact your local Cambridge University Press representative.

  18. Accuracy of blood glucose meters for self-monitoring affects glucose control and hypoglycemia rate in children and adolescents with type 1 diabetes.

    Science.gov (United States)

    Boettcher, Claudia; Dost, Axel; Wudy, Stefan A; Flechtner-Mors, Marion; Borkenstein, Martin; Schiel, Ralf; Weitzel, Dieter; Bechtold-Dalla Pozza, Susanne; Wolf, Johannes; Holl, Reinhard W

    2015-04-01

    This study investigated the accuracy of blood glucose meters for self-monitoring and its influence on glycated hemoglobin (HbA1c) levels and the frequency of hypoglycemic coma. Self-measured and simultaneously obtained laboratory blood glucose values from 9,163 patients with type 1 diabetes glucose control and hypoglycemia rates. Depending on the respective subgroup (defined by sex, age, duration of diabetes, mode of insulin therapy), 78.7-94.7% of the self-monitoring of blood glucose (SMBG) values met the old and 79.7-88.6% met the new ISO criteria. In Clarke and Parkes error grid analyses, the percentages of SMBG values in Zone A ranged between 92.8% and 94.6% (Clarke) and between 92.2% and 95.0% (Parkes). The patient group with SMBG devices measuring "far too low" (compared with the laboratory-obtained glucose levels) presented with a higher HbA1c level than those measuring "far too high," "too high," "identical/almost identical," or "too low" (based on quintiles of deviation). Performing "far too high" was associated with the highest rate of hypoglycemic coma in comparison with the other deviation quintiles. This study showed that current SMBG devices fulfilled neither the previous nor the new ISO criteria. Large deviations of the SMBG values from the "true" glucose levels resulted in higher HbA1c levels and markedly increased rates of hypoglycemic events.

  19. Metal–metal multiple bonded intermediates in catalysis

    Indian Academy of Sciences (India)

    type structure are exceptional catalysts for a broad range of organic transformations. I review here the recent efforts towards the observation and characterization of intermediates in these reactions that have previously eluded detection.

  20. Supersymmetry and intermediate symmetry breaking in SO(10) superunification

    International Nuclear Information System (INIS)

    Asatryan, H.M.; Ioannisyan, A.N.

    1985-01-01

    A scheme of simultaneous breakdown of intermediate symmetry SO(10) → SU(3)sub(c) x U(1) x SU(2)sub(L) x SU(2)sub(R) and supersymmetry by means of a single scale parameter is suggested. This intermediate symmetry, which is preferable physically, owing to the broken supersymmetry has a minimum lying lower than SU(4) x SU(2)sub(L) x SU(2)sub(R). The intermediate symmetry is broken by the vacuum expectation value of the Higgs superfields. Owing to the quantum corrections the potential minimum turns out to correspond to breakdown of the intermediate symmetry up to the standard group SU(3)sub(c) x SU(2)sub(L) x U(1)sub(y). The value of the Weinberg angle is less than that in the supersymmetric SU(5) model and agrees with the experiment