Long-Term Cost-Effectiveness of Insulin Glargine Versus Neutral Protamine Hagedorn Insulin for Type 2 Diabetes in Thailand.

Science.gov (United States)

Permsuwan, Unchalee; Chaiyakunapruk, Nathorn; Dilokthornsakul, Piyameth; Thavorn, Kednapa; Saokaew, Surasak

2016-06-01

Even though Insulin glargine (IGlar) has been available and used in other countries for more than a decade, it has not been adopted into Thai national formulary. This study aimed to evaluate the long-term cost effectiveness of IGlar versus neutral protamine Hagedorn (NPH) insulin in type 2 diabetes from the perspective of Thai Health Care System. A validated computer simulation model (the IMS CORE Diabetes Model) was used to estimate the long-term projection of costs and clinical outcomes. The model was populated with published characteristics of Thai patients with type 2 diabetes. Baseline risk factors were obtained from Thai cohort studies, while relative risk reduction was derived from a meta-analysis study conducted by the Canadian Agency for Drugs and Technology in Health. Only direct costs were taken into account. Costs of diabetes management and complications were obtained from hospital databases in Thailand. Both costs and outcomes were discounted at 3 % per annum and presented in US dollars in terms of 2014 dollar value. Incremental cost-effectiveness ratio (ICER) was calculated. One-way and probabilistic sensitivity analyses were also performed. IGlar is associated with a slight gain in quality-adjusted life years (0.488 QALYs), an additional life expectancy (0.677 life years), and an incremental cost of THB119,543 (US$3522.19) compared with NPH insulin. The ICERs were THB244,915/QALY (US$7216.12/QALY) and THB176,525/life-year gained (LYG) (US$5201.09/LYG). The ICER was sensitive to discount rates and IGlar cost. At the acceptable willingness to pay of THB160,000/QALY (US$4714.20/QALY), the probability that IGlar was cost effective was less than 20 %. Compared to treatment with NPH insulin, treatment with IGlar in type 2 diabetes patients who had uncontrolled blood glucose with oral anti-diabetic drugs did not represent good value for money at the acceptable threshold in Thailand.

Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents.

Science.gov (United States)

Lira, Fábio S; Rosa, Jose C; Pimentel, Gustavo D; Santos, Ronaldo V; Carnier, June; Sanches, Priscila L; de Piano, Aline; de Souza, Claudio T; Tock, Lian; Tufik, Sergio; de Mello, Marco T; Seelaender, Marília; Oller do Nascimento, Claudia M; Oyama, Lila M; Dâmaso, Ana R

2012-09-18

The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15-19 y) with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR). The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways.

Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents

Directory of Open Access Journals (Sweden)

Lira Fábio S

2012-09-01

Full Text Available Abstract Aim The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. Design The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15–19 y with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR. Results The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. Conclusions The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways.

Oral administration of insulin by means of liposomes in animal experiments

International Nuclear Information System (INIS)

Tragl, K.H.; Pohl, A.; Kinast, H.

1979-01-01

Liposomes are an effective vehicle for the oral administration of insulin. They are prepared from lipid emulsions by sonication and particles of homogeneous size are generated by elution through sepharose columns. Liposomes are taken up into the gastric mucosa by endocytosis and then transported to the liver via the portal circulation. Oral administration of 10 U insulin/kg body weight to rats is followed by a reduction in blood glucose to 67% of the initial value. When liposome-trapped insulin was injected intravenously a decrease in blood glucose to 40% of the initial value was obtained by the administration of 5 IU insulin/kg body weight. While the effect of orally-administered liposome-trapped insulin is obvious, the problems of standardization of the insulin content of the liposomes and the great variability of liposome uptake into the gastric mucosa by endocytosis remain unsolved. (author)

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

DEFF Research Database (Denmark)

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

2016-01-01

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

7 CFR 801.2 - Meaning of terms.

Science.gov (United States)

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Meaning of terms. 801.2 Section 801.2 Agriculture... FOR GRAIN INSPECTION EQUIPMENT § 801.2 Meaning of terms. (a) Construction. Words used in the singular... used in this part 801. For the purposes of this part, the following terms shall have the meanings given...

The nature and meaning of insulin pump use in emerging adults with type 1 diabetes.

Science.gov (United States)

Hood, Donna G; Duke, Gloria

2015-05-01

Objective. The purpose of this study is to investigate the meaning of living with an insulin pump for the management of type 1 diabetes during the period of emerging adulthood. Through a phenomenological narrative, this study contributes to the reflective understanding of the everyday life experiences of this population. Methods. A hermeneutic phenomenological design was used for this study of nine emerging adults (aged 19-24 years). Data were generated through face-to-face interviews and analyzed using the phenomenological approach of Max van Manen. Results. Four themes represent the essence of the day-to-day experiences of these emerging adults: seeking control, becoming responsible, staying connected, and accepting me. Conclusions. An in-depth understanding of the meaning of daily experiences with insulin pump technology has the potential to promote a developmentally appropriate approach to this age-group. The human understanding gained through this study is essential to the development of evidence-based practice guidelines and resources for this vulnerable population.

The effects of increasing doses of 2 preparations of long-acting insulin on short-term plasma profiles of glucose and insulin in lactating dairy cows.

Science.gov (United States)

Winkelman, L A; Overton, T R

2012-12-01

Two experiments were conducted to investigate effects of administering increasing doses of 2 different preparations of long-acting insulin on the 24-h profiles of plasma glucose and insulin concentrations in mid lactation dairy cows. The 2 separately analyzed experiments investigated the effects administering either Humulin N (H), a neutral protamine Hagedorn insulin, or insulin glargine (Lantus, L), an insulin analog, at doses of 0 (control), 0.1, 0.2, and 0.4 IU/kg of body weight in a randomized complete block design. Sixteen cows (237±11 d in milk for H; 213±10 d in milk for L; mean ± SD) were used for each insulin preparation, resulting in n=4 for each dose within insulin preparation. Cows were fitted with a single jugular catheter on the day before the study. On the day of the study, cows were given treatments by subcutaneous injection of either sterile water or the designated insulin type and dose. Blood samples were taken hourly from the jugular catheter. Subcutaneous injection of both H and L resulted in linear decreases in plasma glucose concentrations, increased area under the curve, and decreased nadir for plasma glucose following administration of the insulin preparations. Plasma insulin concentration linearly increased with increasing dose of H. Though elevated concentrations of insulin were measurable in cows treated with H, they were not measurable in cows treated with L. Attempts to measure overall insulin concentrations and metabolites of L by a commercially available ELISA and a commercially available RIA kit were not successful and did not retrieve values that we felt truly represented the amount of insulin activity exhibited during this treatment. Both long-acting insulin preparations elicited insulin-like activity in lactating dairy cows, as evidenced by reduced plasma glucose concentrations. Given these results, the potential exists to use both H and L to study the effects of insulin in mid lactation dairy cows without the confounding

Insulin sensitivity deteriorates after short-term lifestyle intervention in the insulin sensitive phenotype of obesity.

Science.gov (United States)

Gilardini, Luisa; Vallone, Luciana; Cottafava, Raffaella; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

2012-01-01

To investigate the effects of a 3-month lifestyle intervention on insulin sensitivity and its related cardiometabolic factors in obese patients. Anthropometry, body composition, oral glucose tolerance test, lipids, alanine aminotransferase, insulin sensitivity (insulinogenic index (ISI), homeostasis model assessment, β-cell performance (disposition index)) were evaluated in 263 obese women and 93 obese men before and after 3 months of hypocaloric low fat/high protein diet associated with physical activity 30 min/day. Patients were divided into 3 groups according to the intervention-induced ISI changes: group 1 (decrease), group 2 (stability) and group 3 (increase). Insulin sensitivity and the disposition index were significantly higher before the intervention in group 1 than in group 3. BMI, waist circumference, and fat mass significantly decreased in groups 1 and 3 in both sexes. β-cell performance decreased in group 1 and increased in group 3. Metabolic variables improved in group 3, whereas glucose levels increased in women of group 1. The post-intervention insulin sensitivity was lower in group 1 than in group 3. Lifestyle intervention induces changes in insulin sensitivity and metabolic factors that depend on the pre-intervention degree of insulin sensitivity. Weight loss leads to metabolic benefits in insulin-resistant, obese patients, whereas it may paradoxically worsen the metabolic conditions in the insulin-sensitive phenotype of obesity. Copyright © 2012 S. Karger GmbH, Freiburg.

Short-term insulin treatment prevents the diabetogenic action of streptozotocin in rats

DEFF Research Database (Denmark)

Thulesen, J; Orskov, C; Holst, J J

1997-01-01

Streptozotocin, which induces diabetes mellitus in experimental animals, has been reported to be taken up by beta-cells by means of the glucose transporter 2 (GLUT2) and then reduce the cellular level of NAD+, leading to necrosis of the beta-cells. We investigated the effect of insulin pretreatme...

Glucose-lowering effect and glycaemic variability of insulin glargine, insulin detemir and insulin lispro protamine in people with type 1 diabetes.

Science.gov (United States)

Derosa, G; Franzetti, I; Querci, F; Romano, D; D'Angelo, A; Maffioli, P

2015-06-01

To compare, using a continuous glucose monitoring (CGM) system, the effect on glycaemic variability of insulin glargine, detemir and lispro protamine. A total of 49 white people with type 1 diabetes, not well controlled by three times daily insulin lispro, taken for at least 2 months before study and on a stable dose, were enrolled. The study participants were randomized to add insulin glargine, detemir or lispro protamine, once daily, in the evening. We used a CGM system, the iPro Digital Recorder (Medtronic MiniMed, Northridge, CA, USA) for 1 week. Glycaemic control was assessed according to mean blood glucose values, the area under the glucose curve above 3.9 mmol/l (AUC(>3.9)) or above 10.0 mmol/l (AUC(>10.0)), and the percentage of time spent with glucose values >3.9 or >10.0 mmol/l. Intraday glycaemic variability was assessed using standard deviation (s.d.) values, the mean amplitude of glycaemic excursions and continuous overlapping of net glycaemic action. Day-to-day glycaemic variability was assessed using the mean of daily differences. The s.d. was found to be significantly lower with insulin lispro protamine and glargine compared with insulin detemir. AUC(>3.9) was higher and AUC(>10.0) was lower with insulin lispro protamine and glargine compared with detemir. The mean amplitude of glycaemic excursions and continuous overlapping net glycaemic action values were lower with insulin lispro protamine and glargine compared with detemir. In addition, the mean of daily differences was significantly lower with insulin lispro protamine and glargine compared with detemir. Fewer hypoglycaemic events were recorded during the night-time with insulin lispro protamine compared with glargine and detemir. The results suggest that insulin lispro protamine and glargine are more effective than detemir in reducing glycaemic variability and improving glycaemic control in people with type 1 diabetes. Insulin lispro protamine seems to lead to fewer hypoglycaemic

Impaired autoregulation of cerebral blood flow in long-term type I (insulin-dependent) diabetic patients with nephropathy and retinopathy

DEFF Research Database (Denmark)

Kastrup, J; Rørsgaard, S; Parving, H H

1986-01-01

Autoregulation of cerebral blood flow, i.e., the maintenance of cerebral blood flow within narrow limits during changes in arterial perfusion pressure, was studied in nine healthy control subjects and in 12 long-term Type I (insulin-dependent) diabetic patients with clinical microangiopathy...... the previous findings suggesting that autoregulation of cerebral blood flow is impaired in some long-term Type I diabetic patients with clinical microangiopathy (arteriolar hyalinosis)........ Cerebral blood flow was measured by the intravenous 133Xenon method. Mean arterial blood pressure was elevated approximately 30 mmHg by intravenous infusion of angiotensin amide II and lowered about 10 mmHg by intravenous infusion of trimethaphan camsylate. In the control subjects the flow/pressure curve...

Interaction between exogenous insulin, endogenous insulin, and glucose in type 2 diabetes patients.

Science.gov (United States)

Janukonyté, Jurgita; Parkner, Tina; Bruun, Niels Henrik; Lauritzen, Torsten; Christiansen, Jens Sandahl; Laursen, Torben

2015-05-01

Little is known about the influence of exogenous insulin and actual glucose levels on the release of endogenous insulin in insulin-treated type 2 diabetes mellitus (T2DM) patients. This study investigated the interaction among serum endogenous insulin (s-EI), serum exogenous insulin aspart (s-IAsp), and blood glucose levels in an experimental short-term crossover design. Eight T2DM patients (63.52 years old; range, 49-69 years; mean body mass index, 28.8±3.8 kg/m(2)) were randomized to treatment with individual fixed doses of insulin aspart (0.5-1.5 IU/h) as a continuous subcutaneous insulin infusion (CSII) during a 10-h period on two occasions with different duration of hyperglycemia: (1) transient hyperglycemia for 2 h (visit TH) and (2) continuous hyperglycemia for 12 h (visit CH). During steady state the variances of plasma glucose (p-glucose), s-IAsp, and s-EI were equal within visit TH and within visit CH, but variances were significantly higher during visit CH compared with visit TH. The s-IAsp reached lower levels at visit CH compared with visit TH (test for slope=1, P=0.005). The s-EI depended on p-glucose in a nonlinear fashion during the first 100 min of both visits when s-IAsp was undetectable (adjusted R(2)=0.9). A complex but statistically significant interaction among s-IAsp, s-EI, p-glucose, and patients was observed during measurable s-IAsp levels (adjusted R(2)=0.70). Endogenous and exogenous insulin showed higher variation during continuous hyperglycemia. Significantly lower levels of exogenous insulin were observed following CSII during continuous hyperglycemia compared with transient hyperglycemia. Endogenous insulin levels could in a complex way be explained by an individual interaction among p-glucose and serum exogenous insulin, if present.

Long-term corticosterone exposure decreases insulin sensitivity and induces depressive-like behaviour in the C57BL/6NCrl mouse.

Directory of Open Access Journals (Sweden)

Eva L van Donkelaar

Full Text Available Chronic stress or long-term administration of glucocorticoids disrupts the hypothalamus-pituitary-adrenal system leading to continuous high levels of glucocorticoids and insulin resistance (IR. This pre-diabetic state can eventually develop into type 2 diabetes mellitus and has been associated with a higher risk to develop depressive disorders. The mechanisms underlying the link between chronic stress, IR and depression remains unclear. The present study aimed to establish a stress-depression model in mice to further study the effects of stress-induced changes upon insulin sensitivity and behavioural consequences. A pilot study was conducted to establish the optimal administration route and a pragmatic measurement of IR. Subsequently, 6-month-old C57BL/6NCrl mice were exposed to long-term oral corticosterone treatment via the drinking water. To evaluate insulin sensitivity changes, blood glucose and plasma insulin levels were measured at different time-points throughout treatment and mice were behaviourally assessed in the elevated zero maze (EZM, forced swimming test (FST and open field test to reveal behavioural changes. Long-term corticosterone treatment increased body weight and decreased insulin sensitivity. The latter was revealed by a higher IR index and increased insulin in the plasma, whereas blood glucose levels remained unchanged. Corticosterone treatment induced longer immobility times in the FST, reflecting depressive-like behaviour. No effects were observed upon anxiety as measured in the EZM. The effect of the higher body weight of the CORT treated animals at time of testing did not influence behaviour in the EZM or FST, as no differences were found in general locomotor activity. Long-term corticosterone treatment via the drinking water reduces insulin sensitivity and induces depressive-like behaviour in the C57BL/6 mouse. This mouse model could thus be used to further explore the underlying mechanisms of chronic stress-induced T2

Consolidation of long-term memory by insulin in Lymnaea is not brought about by changing the number of insulin receptors

OpenAIRE

Hatakeyama, Dai; Okuta, Akiko; Otsuka, Emi; Lukowiak, Ken; Ito, Etsuro

2013-01-01

The pond snail Lymnaea stagnalis learns taste aversion and consolidates it into long-term memory (LTM). This is referred to as conditioned taste aversion (CTA). The superfusion of molluscan insulin-related peptides (MIPs) over the isolated snail brain causes a long-term enhancement of synaptic input between the cerebral giant cell and the B1 buccal motor neuron. This enhancement is hypothesized to underlie CTA. The synaptic enhancement caused by the superfusion of MIPs can be blocked by the a...

Acute and long-term administration of palmitoylcarnitine induces muscle-specific insulin resistance in mice.

Science.gov (United States)

Liepinsh, Edgars; Makrecka-Kuka, Marina; Makarova, Elina; Volska, Kristine; Vilks, Karlis; Sevostjanovs, Eduards; Antone, Unigunde; Kuka, Janis; Vilskersts, Reinis; Lola, Daina; Loza, Einars; Grinberga, Solveiga; Dambrova, Maija

2017-09-10

Acylcarnitine accumulation has been linked to perturbations in energy metabolism pathways. In this study, we demonstrate that long-chain (LC) acylcarnitines are active metabolites involved in the regulation of glucose metabolism in vivo. Single-dose administration of palmitoylcarnitine (PC) in fed mice induced marked insulin insensitivity, decreased glucose uptake in muscles, and elevated blood glucose levels. Increase in the content of LC acylcarnitine induced insulin resistance by impairing Akt phosphorylation at Ser473. The long-term administration of PC using slow-release osmotic minipumps induced marked hyperinsulinemia, insulin resistance, and glucose intolerance, suggesting that the permanent accumulation of LC acylcarnitines can accelerate the progression of insulin resistance. The decrease of acylcarnitine content significantly improved glucose tolerance in a mouse model of diet-induced glucose intolerance. In conclusion, we show that the physiological increase in content of acylcarnitines ensures the transition from a fed to fasted state in order to limit glucose metabolism in the fasted state. In the fed state, the inability of insulin to inhibit LC acylcarnitine production induces disturbances in glucose uptake and metabolism. The reduction of acylcarnitine content could be an effective strategy to improve insulin sensitivity. © 2017 BioFactors, 43(5):718-730, 2017. © 2017 The Authors BioFactors published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology.

Short-term intensive insulin therapy in type 2 diabetes mellitus: a systematic review and meta-analysis.

Science.gov (United States)

Kramer, Caroline Kaercher; Zinman, Bernard; Retnakaran, Ravi

2013-09-01

Studies have shown that, when implemented early in the course of type 2 diabetes mellitus, treatment with intensive insulin therapy for 2-3 weeks can induce a glycaemic remission, wherein patients are able to maintain normoglycaemia without any anti-diabetic medication. We thus did a systematic review and meta-analysis of interventional studies to assess the effect of short-term intensive insulin therapy on the pathophysiological defects underlying type 2 diabetes mellitus (pancreatic β-cell dysfunction and insulin resistance) and identify clinical predictors of remission. We identified studies published between 1950 and Nov 19, 2012, which assessed the effect of intensive insulin therapy on β-cell function or insulin resistance, or both, or assessed long-term drug-free glycaemic remission in adults aged 18 years or older with newly diagnosed type 2 diabetes mellitus. We calculated pooled estimates by random-effects model. This study is registered with International Prospective Register of Systematic Reviews, number CRD42012002829. We identified 1645 studies of which seven fulfilled inclusion criteria (n=839 participants). Five studies were non-randomised. A pooled analysis of the seven studies showed a post-intensive insulin therapy increase in Homeostasis Model Assessment of β-cell function as compared with baseline (1·13, 95% CI 1·02 to 1·25) and a decrease in Homeostasis Model Assessment of Insulin Resistance (-0·57, -0·84 to -0·29). In the four studies that assessed glycaemic remission (n=559 participants), the proportion of participants in drug-free remission was about 66·2% (292 of 441 patients) after 3 months of follow-up, about 58·9% (222 of 377 patients) after 6 months, about 46·3% (229 of 495 patients) after 12 months, and about 42·1% (53 of 126 patients) after 24 months. Patients who achieved remission had higher body-mass index than those who did not achieve remission (1·06 kg/m(2), 95% CI 0·55 to 1·58) and lower fasting plasma glucose

The effect of glucagon infusion on kidney function in short-term insulin-dependent juvenile diabetics

DEFF Research Database (Denmark)

Parving, H H; Christiansen, J S; Noer, I

1980-01-01

Kidney function was studied in nine, metabolically well controlled, short-term insulin-dependent male diabetics before and during glucagon infusion of 4 to 5 and 8 to 10 ng/kg/min. Glomerular filtration rate, effective renal plasma flow (steady-state infusion technique, with urinary collections......, using 125I-iothalamate and 131I-iodohippurate), and urinary albumin and beta 2-microglobulin excretion rates were measured. The mean plasma glucagon concentration increased during infusion from 254 +/- 19 pg/ml to 440 +/- 31 pg/ml (low dose) and 730 +/- 52 pg/ml (high dose). Glomerular filtration rate...... increased in all subjects from 133 +/- 5 before the glucagon infusion to 141 +/- 4 with the low dose, and 148 +/- 7 ml/min/1.73 m2 with the high dose (p

Long-term tolerability of inhaled human insulin (Exubera) in patients with poorly controlled type 2 diabetes

DEFF Research Database (Denmark)

Barnett, A H; Lange, P; Dreyer, M

2007-01-01

OBJECTIVE: Inhaled human insulin (Exubera; EXU) has shown encouraging tolerability in short-term trials. We evaluated the safety profile of EXU after long-term exposure. DESIGN: In two, open-label, 2-year studies patients poorly controlled on a sulphonylurea were randomised to adjunctive EXU...... or metformin (study 1) and patients poorly controlled on metformin were randomised to adjunctive EXU or the sulphonylurea, glibenclamide (study 2). PATIENTS: The studies included 446 (study 1) and 476 (study 2) patients with type 2 diabetes, no clinically significant respiratory disease and glycosylated....... There was no discernable effect of long-term EXU therapy on pulmonary gas exchange. Insulin antibody binding reached a plateau at 6 months and did not correlate with HbA(1c) or lung function changes. Glycaemic control was maintained over 2 years. CONCLUSIONS: Exubera was well tolerated during long-term use. Pulmonary...

Insulin Resistance Induced by Hyperinsulinemia Coincides with a Persistent Alteration at the Insulin Receptor Tyrosine Kinase Domain

Science.gov (United States)

Catalano, Karyn J.; Maddux, Betty A.; Szary, Jaroslaw; Youngren, Jack F.; Goldfine, Ira D.; Schaufele, Fred

2014-01-01

Insulin resistance, the diminished response of target tissues to insulin, is associated with the metabolic syndrome and a predisposition towards diabetes in a growing proportion of the worldwide population. Under insulin resistant states, the cellular response of the insulin signaling pathway is diminished and the body typically responds by increasing serum insulin concentrations to maintain insulin signaling. Some evidence indicates that the increased insulin concentration may itself further dampen insulin response. If so, insulin resistance would worsen as the level of circulating insulin increases during compensation, which could contribute to the transition of insulin resistance to more severe disease. Here, we investigated the consequences of excess insulin exposure to insulin receptor (IR) activity. Cells chronically exposed to insulin show a diminished the level of IR tyrosine and serine autophosphorylation below that observed after short-term insulin exposure. The diminished IR response did not originate with IR internalization since IR amounts at the cell membrane were similar after short- and long-term insulin incubation. Förster resonance energy transfer between fluorophores attached to the IR tyrosine kinase (TK) domain showed that a change in the TK domain occurred upon prolonged, but not short-term, insulin exposure. Even though the altered ‘insulin refractory’ IR TK FRET and IR autophosphorylation levels returned to baseline (non-stimulated) levels after wash-out of the original insulin stimulus, subsequent short-term exposure to insulin caused immediate re-establishment of the insulin-refractory levels. This suggests that some cell-based ‘memory’ of chronic hyperinsulinemic exposure acts directly at the IR. An improved understanding of that memory may help define interventions to reset the IR to full insulin responsiveness and impede the progression of insulin resistance to more severe disease states. PMID:25259572

Insulin resistance induced by hyperinsulinemia coincides with a persistent alteration at the insulin receptor tyrosine kinase domain.

Directory of Open Access Journals (Sweden)

Karyn J Catalano

Full Text Available Insulin resistance, the diminished response of target tissues to insulin, is associated with the metabolic syndrome and a predisposition towards diabetes in a growing proportion of the worldwide population. Under insulin resistant states, the cellular response of the insulin signaling pathway is diminished and the body typically responds by increasing serum insulin concentrations to maintain insulin signaling. Some evidence indicates that the increased insulin concentration may itself further dampen insulin response. If so, insulin resistance would worsen as the level of circulating insulin increases during compensation, which could contribute to the transition of insulin resistance to more severe disease. Here, we investigated the consequences of excess insulin exposure to insulin receptor (IR activity. Cells chronically exposed to insulin show a diminished the level of IR tyrosine and serine autophosphorylation below that observed after short-term insulin exposure. The diminished IR response did not originate with IR internalization since IR amounts at the cell membrane were similar after short- and long-term insulin incubation. Förster resonance energy transfer between fluorophores attached to the IR tyrosine kinase (TK domain showed that a change in the TK domain occurred upon prolonged, but not short-term, insulin exposure. Even though the altered 'insulin refractory' IR TK FRET and IR autophosphorylation levels returned to baseline (non-stimulated levels after wash-out of the original insulin stimulus, subsequent short-term exposure to insulin caused immediate re-establishment of the insulin-refractory levels. This suggests that some cell-based 'memory' of chronic hyperinsulinemic exposure acts directly at the IR. An improved understanding of that memory may help define interventions to reset the IR to full insulin responsiveness and impede the progression of insulin resistance to more severe disease states.

Involvement of insulin-like peptide in long-term synaptic plasticity and long-term memory of the pond snail Lymnaea stagnalis.

Science.gov (United States)

Murakami, Jun; Okada, Ryuichi; Sadamoto, Hisayo; Kobayashi, Suguru; Mita, Koichi; Sakamoto, Yuki; Yamagishi, Miki; Hatakeyama, Dai; Otsuka, Emi; Okuta, Akiko; Sunada, Hiroshi; Takigami, Satoshi; Sakakibara, Manabu; Fujito, Yutaka; Awaji, Masahiko; Moriyama, Shunsuke; Lukowiak, Ken; Ito, Etsuro

2013-01-02

The pond snail Lymnaea stagnalis is capable of learning taste aversion and consolidating this learning into long-term memory (LTM) that is called conditioned taste aversion (CTA). Previous studies showed that some molluscan insulin-related peptides (MIPs) were upregulated in snails exhibiting CTA. We thus hypothesized that MIPs play an important role in neurons underlying the CTA-LTM consolidation process. To examine this hypothesis, we first observed the distribution of MIP II, a major peptide of MIPs, and MIP receptor and determined the amounts of their mRNAs in the CNS. MIP II was only observed in the light green cells in the cerebral ganglia, but the MIP receptor was distributed throughout the entire CNS, including the buccal ganglia. Next, when we applied exogenous mammalian insulin, secretions from MIP-containing cells or partially purified MIPs, to the isolated CNS, we observed a long-term change in synaptic efficacy (i.e., enhancement) of the synaptic connection between the cerebral giant cell (a key interneuron for CTA) and the B1 motor neuron (a buccal motor neuron). This synaptic enhancement was blocked by application of an insulin receptor antibody to the isolated CNS. Finally, injection of the insulin receptor antibody into the snail before CTA training, while not blocking the acquisition of taste aversion learning, blocked the memory consolidation process; thus, LTM was not observed. These data suggest that MIPs trigger changes in synaptic connectivity that may be correlated with the consolidation of taste aversion learning into CTA-LTM in the Lymnaea CNS.

Interaction between exogenous insulin, endogenous insulin, and glucose in type 2 diabetes patients

DEFF Research Database (Denmark)

Janukonyté, Jurgita; Parkner, Tina; Bruun, Niels Henrik

2015-01-01

insulin aspart (s-IAsp), and blood glucose levels in an experimental short-term crossover design. STUDY DESIGN AND METHODS: Eight T2DM patients (63.52 years old; range, 49-69 years; mean body mass index, 28.8±3.8 kg/m2) were randomized to treatment with individual fixed doses of insulin aspart (0.5-1.5 IU......-IAsp, and s-EI were equal within visit TH and within visit CH, but variances were significantly higher during visit CH compared with visit TH. The s-IAsp reached lower levels at visit CH compared with visit TH (test for slope=1, P=0.005). The s-EI depended on p-glucose in a nonlinear fashion during the first...

Impact of insulin pump on quality of life of diabetic patients

Directory of Open Access Journals (Sweden)

Haider Ghazanfar

2016-01-01

Full Text Available Aim: Diabetes is an emerging health problem, both in developing and developed countries and has an enormous economic and social impact. The objective of our study was to find the impact of insulin pump on the quality of life of patients with type 2 diabetes (T2D and compare it to the quality of life of patients with T2D using an insulin pen. Subjects and Methods: This is a case–control study which was conducted among patients with T2D presenting between November 2014 and November 2015. A total of 83 patients with T2D, using insulin pump were enrolled in the study as cases and 322 patients with T2D not using insulin pump but using insulin pens were enrolled as controls. Short form-36 quality of life questionnaire was used for data collection. Results: Mean age of patients using insulin pump was 52.49 ± 9.28 while the mean age of patients not using insulin pump was 54.72 ± 16.87. Mean score of all domains in the questionnaire was found to be higher in patients using insulin pump as compared to patients not using insulin pumps (P < 0.05. In 81.1% of the patients, the insulin pump decreased the frequency of hypoglycemic episodes. Conclusion: Insulin pump has significantly improved the quality of life of patients in terms of better self-esteem, decreased stress, and better mood. It has resulted in improved physical health, meal time flexibility, and ease of travel. It allows patient to have more active participation in social and recreational activities improving their personal and family life.

Long term rebaudioside A treatment does not alter circadian activity rhythms, adiposity, or insulin action in male mice.

Directory of Open Access Journals (Sweden)

Thomas H Reynolds

Full Text Available Obesity is a major public health problem that is highly associated with insulin resistance and type 2 diabetes, two conditions associated with circadian disruption. To date, dieting is one of the only interventions that result in substantial weight loss, but restricting caloric intake is difficult to maintain long-term. The use of artificial sweeteners, particularly in individuals that consume sugar sweetened beverages (energy drinks, soda, can reduce caloric intake and possibly facilitate weight loss. The purpose of the present study was to examine the effects of the artificial sweetener, rebaudioside A (Reb-A, on circadian rhythms, in vivo insulin action, and the susceptibility to diet-induced obesity. Six month old male C57BL/6 mice were assigned to a control or Reb-A (0.1% Reb-A supplemented drinking water group for six months. Circadian wheel running rhythms, body weight, caloric intake, insulin action, and susceptibility to diet-induced obesity were assessed. Time of peak physical activity under a 12:12 light-dark (LD cycle, mean activity levels, and circadian period in constant dark were not significantly different in mice that consumed Reb-A supplemented water compared to normal drinking water, indicating that circadian rhythms and biological clock function were unaltered. Although wheel running significantly reduced body weight in both Reb-A and control mice (P = 0.0001, consuming Reb-A supplemented water did not alter the changes in body weight following wheel running (P = 0.916. In vivo insulin action, as assessed by glucose, insulin, and pyruvate tolerance tests, was not different between mice that consumed Reb-A treated water compared to normal drinking water. Finally, Reb-A does not appear to change the susceptibility to diet-induced obesity as both groups of mice gained similar amounts of body weight when placed on a high fat diet. Our results indicate that consuming Reb-A supplemented water does not promote circadian disruption

What Do Mental Terms Mean?

Science.gov (United States)

Moore, Jay

2010-01-01

Psychologists and philosophers have long been interested in two questions: (a) What do mental terms mean? and (b) what role do mental terms play in explanations of behavior? In the current sketch I review how mediational neobehaviorism, cognitive psychology, and the radical behaviorism of B. F. Skinner address these questions. In so doing, I seek…

Concentrated insulins: the new basal insulins

Directory of Open Access Journals (Sweden)

Lamos EM

2016-03-01

Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

Single-donor islet transplantation and long-term insulin independence in select patients with type 1 diabetes mellitus.

Science.gov (United States)

Al-Adra, David P; Gill, Richdeep S; Imes, Sharleen; O'Gorman, Doug; Kin, Tatsuya; Axford, Sara J; Shi, Xinzhe; Senior, Peter A; Shapiro, A M James

2014-11-15

Islet transplantation is a recognized treatment option for select patients with type I diabetes mellitus. However, islet infusions from multiple donors are often required to achieve insulin independence. Ideally, insulin independence would be achieved routinely with only a single donor. Identification of factors associated with insulin independence after single-donor islet transplantation may help to select recipient-donor combinations with the highest probability of success. Subjects undergoing islet transplantation at a single center (Edmonton, Canada) between March 1999 and August 2013 were included. Recipient, donor, and transplant characteristics were collected and compared between recipients who became insulin independent after one islet transplantation and those who did not. Thirty-one patients achieved insulin independence after a single-donor islet transplantation, and 149 did not. Long-term insulin-free survival was not different between the groups. Factors significantly associated with single-donor success included recipient age, insulin requirement at baseline, donor weight, donor body mass index, islet transplant mass, and peritransplant heparin and insulin administration. On multivariate analysis, pretransplantation daily insulin requirements, the use of peritransplantation heparin and insulin infusions, and islet transplant mass remained significant. We have identified clinically relevant differences defining the achievement of insulin independence after single-donor transplantation. Based on these differences, a preoperative insulin requirement of less than 0.6 U/kg per day and receiving more than 5,646 islet equivalents (IEQ)/kg have a sensitivity of 84% and 71% and specificity of 50% and 50%, respectively, for insulin independence after single-donor islet transplantation. With ideal patient selection, this finding could potentially increase single-donor transplantation success and may be especially relevant for presensitized subjects or those who

Short-acting insulin analogues versus regular human insulin for adults with type 1 diabetes mellitus.

Science.gov (United States)

Fullerton, Birgit; Siebenhofer, Andrea; Jeitler, Klaus; Horvath, Karl; Semlitsch, Thomas; Berghold, Andrea; Plank, Johannes; Pieber, Thomas R; Gerlach, Ferdinand M

2016-06-30

the reporting of methods and results.The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value 1; 2608 participants; 9 trials; low quality evidence) in favour of insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the insulin analogue, insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable.We also found no clear evidence for a substantial effect of insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Our analysis suggests only a minor benefit of short-acting insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of short acting insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

The influence of short-term endurance training on the insulin blood level, binding, and degradation of 125I-insulin by erythrocyte receptors in patients after myocardial infarction.

Science.gov (United States)

Dylewicz, P; Przywarska, I; Szcześniak, L; Rychlewski, T; Bieńkowska, S; Długiewicz, I; Wilk, M

1999-01-01

This study was directed toward establishing whether and to what extent, short-term endurance training influences the insulin blood level, and the binding and degradation of 125I-insulin by erythrocyte receptors in patients undergoing rehabilitation after myocardial infarction. The study was conducted in a group of 60 patients who had had myocardial infarction within the past 1.5 to 3 months and who did not have arterial hypertension and diabetes mellitus. All the patients took a symptom-limited cardiopulmonary exercise test. Before and after the test, venous blood was collected to determine lactic acid and insulin blood levels as well as the binding and degradation of 125I-insulin. The study group was randomized into two subgroups. One subgroup entered into a 3-week in-patient rehabilitation course. The control group was discharged from the hospital and was given no recommendations for physical exercise. The same investigation was repeated 3 weeks later. In the patients (50%) with hyperinsulinemia (insulin resistance index, > 10 microIU/mL), which was detected during the first investigation, insulin blood level decreased from 23.9 +/- 4.4 to 15.0 +/- 1.9 microIU/mL (P endurance training period during rehabilitation after myocardial infarction reduces insulin resistance in patients with hyperinsulinemia.

Therapeutic fasting in patients with metabolic syndrome and impaired insulin resistance.

Science.gov (United States)

Stange, Rainer; Pflugbeil, Christine; Michalsen, Andreas; Uehleke, Bernhard

2013-01-01

In this study, we evaluated whether a short- to mid-term fasting therapy (7-18 days) might improve insulin resistance according to the homeostasis model assessment for insulin resistance (HOMA-IR), measured during mid-term (80 days) follow-up observation in patients with metabolic syndrome. In this open label observational study in inpatients, criteria of metabolic syndrome were defined. Before medically controlled Buchinger fasting, a wash-out period for hypoglycemic agents was conducted. Further evaluation was carried out on day 80. 25 patients (13 males, 12 females, mean age 61.3 years) were included in this study (mean fasting duration 11.5 days). Out of 16 inpatients with type 2 diabetes, 4 had been treated with metformin, 3 with insulin, and 1 with glimepiride before the intervention. After therapy, body mass index (BMI), fasting insulin, fasting glucose, and HOMA-IR were all significantly reduced. Compared to baseline, HOMA-IR decreased by 33% in all patients, by 38% in patients with type 2 diabetes, and by 23% in patients without diabetes. At day 80, BMI further improved, while other parameters showed complete (insulin) or partial (glucose, HOMA-IR) rebound. At this time, HOMA-IR values showed an only insignificant improvement in 15% of all patients, in 20% of patients with type 2 diabetes, and in 6% of patients without diabetes. There was no correlation between change in BMI and change in HOMA-IR (r(2) = 0.008, baseline minus day 80). No serious side effects were observed. Fasting as a safe and acceptable procedure may cause short- and mid-term improvement of increased insulin resistance (HOMA-IR). Patients with type 2 diabetes benefit more than those without diabetes. A possible clinical significance of this effect should be explored in larger and controlled clinical trials. © 2014 S. Karger GmbH, Freiburg.

Short- and long-term metabolic effects of recombinant human IGF-I treatment in patients with severe insulin resistance and diabetes mellitus

DEFF Research Database (Denmark)

Vestergaard, H; Rossen, M; Urhammer, S A

1997-01-01

In patients suffering from the genetic syndromes of severe insulin resistance it appears that diabetes develops when the adaptive hypersecretion of insulin fails and often these forms of diabetes will be insensitive to insulin treatment. The objective of the present study was to examine......-resistant diabetes mellitus and (b) during a long-term (10 weeks) period with rhIGF-I given once a day in a low dose (40 micrograms/kg body weight) in three of the four patients. Two siblings had known mutations in the tyrosine kinase domain of the insulin receptor and a deletion of exon 17 in part of their insulin......-50%), proinsulin (40-50%) and C-peptide (10-65%) and an improvement in glycaemic control as evaluated by decreased glycosylated haemoglobin and serum fructosamine. During the long-term study period blood glucose-lowering effects of rhIGF-I were seen after 2 weeks of treatment and fasting plasma glucose and serum...

Prediction on long-term mean and mean square pollutant concentrations in an urban atmosphere

Energy Technology Data Exchange (ETDEWEB)

Kumar, S; Lamb, R G; Seinfeld, J H

1976-01-01

The general problem of predicting long-term average (say yearly) pollutant concentrations in an urban atmosphere is formulated. The pollutant concentration can be viewed as a random process, the complete description of which requires knowledge of its probability density function, which is unknown. The mean concentration is the first moment of the concentration distribution, and at present there exist a number of models for predicting the long-term mean concentration of an inert pollutant. The second moment, or mean square concentration, indicates additional features of the distribution, such as the level of fluctuations about the mean. In the paper a model proposed by Lamb for the long-term mean concentration is reviewed, and a new model for prediction of the long-term mean square concentration of an inert air pollutant is derived. The properties and uses of the model are discussed, and the equations defining the model are presented in a form for direct application to an urban area.

Sub-acute insulin therapy does not affect long-term visiospatial ...

African Journals Online (AJOL)

Insulin is a common hypoglycaemic agent used to treat diabetes, but it has also been reported to exert other effects on the body including modulation cognition. Reported findings on insulin effect on learning and memory are scanty and often conflicting. This study was aimed at evaluating the effect of sub-acute insulin ...

[Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study].

Science.gov (United States)

Ribeiro, Maria Estela Bellini; Del Roio Liberatore Junior, Raphael; Custodio, Rodrigo; Martinelli Junior, Carlos Eduardo

2016-01-01

To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Short- and long-term outcomes of metformin compared with insulin alone in pregnancy: a systematic review and meta-analysis.

Science.gov (United States)

Butalia, S; Gutierrez, L; Lodha, A; Aitken, E; Zakariasen, A; Donovan, L

2017-01-01

To assess the short- and long-term maternal and fetal impact of metformin in pregnancy compared with insulin. We performed a comprehensive literature search of MEDLINE, EMBASE, BIOSIS, Cochrane Database of Systematic Reviews and ClinicalTrials.gov. Eligible studies were randomized control trials (RCTs) or follow-up of an RCT that: (1) compared metformin with insulin in pregnancy in women with gestational diabetes mellitus or Type 2 diabetes; and (2) reported maternal or fetal outcomes of interest. Two reviewers extracted the data, evaluated study quality and calculated pooled estimates. Sixteen studies (n = 2165 in quantitative analysis) were included. Metformin lowered the risk of neonatal hypoglycaemia [risk ratio (RR) = 0.63; 95% confidence interval (95% CI), 0.45 to 0.87], large for gestational age babies (RR = 0.80; 95% CI, 0.64 to 0.99), pregnancy-induced hypertension (RR = 0.56; 95% CI, 0.37 to 0.85) and total maternal pregnancy weight gain [mean difference (MD) -2.07; 95% CI -2.88 to -1.27]. Metformin did not increase preterm delivery (RR = 1.18; 95% CI 0.67 to 2.07), small for gestational age babies (RR = 1.20; 95% CI, 0.67 to 2.14), perinatal mortality (RR = 0.82; 95% CI, 0.17 to 3.92) or Caesarean section (RR = 0.97; 95% CI, 0.80 to 1.19). Long-term outcome information is limited. Our review found that metformin had no short-term adverse effects on pregnancy, potential benefits in the neonatal period, but limited long-term follow-up information. Prior to routine use, we recommend further follow-up studies of offspring exposed to metformin in utero. © 2016 Diabetes UK.

Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance.

Science.gov (United States)

Ramon-Krauel, Marta; Pentinat, Thais; Bloks, Vincent W; Cebrià, Judith; Ribo, Silvia; Pérez-Wienese, Ricky; Vilà, Maria; Palacios-Marin, Ivonne; Fernández-Pérez, Antonio; Vallejo, Mario; Téllez, Noèlia; Rodríguez, Miguel Àngel; Yanes, Oscar; Lerin, Carles; Díaz, Rubén; Plosch, Torsten; Tietge, Uwe J F; Jimenez-Chillaron, Josep C

2018-05-29

Postnatal overfeeding increases the risk of chronic diseases later in life, including obesity, insulin resistance, hepatic steatosis, and type 2 diabetes. Epigenetic mechanisms might underlie the long-lasting effects associated with early nutrition. Here we aimed to explore the molecular pathways involved in early development of insulin resistance and hepatic steatosis, and we examined the potential contribution of DNA methylation and histone modifications to long-term programming of metabolic disease. We used a well-characterized mouse model of neonatal overfeeding and early adiposity by litter size reduction. Neonatal overfeeding led to hepatic insulin resistance very early in life that persisted throughout adulthood despite normalizing food intake. Up-regulation of monoacylglycerol O-acyltransferase ( Mogat) 1 conceivably mediates hepatic steatosis and insulin resistance through increasing intracellular diacylglycerol content. Early and sustained deregulation of Mogat1 was associated with a combination of histone modifications that might favor Mogat1 expression. In sum, postnatal overfeeding causes extremely rapid derangements of hepatic insulin sensitivity that remain relatively stable until adulthood. Epigenetic mechanisms, particularly histone modifications, could contribute to such long-lasting effects. Our data suggest that targeting hepatic monoacylglycerol acyltransferase activity during early life might provide a novel strategy to improve hepatic insulin sensitivity and prevent late-onset insulin resistance and fatty liver disease.-Ramon-Krauel, M., Pentinat, T., Bloks, V. W., Cebrià, J., Ribo, S., Pérez-Wienese, R., Vilà, M., Palacios-Marin, I., Fernández-Pérez, A., Vallejo, M., Téllez, N., Rodríguez, M. À., Yanes, O., Lerin, C., Díaz, R., Plosch, T., Tietge, U. J. F., Jimenez-Chillaron, J. C. Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance.

Peripheral insulin resistance and impaired insulin signaling contribute to abnormal glucose metabolism in preterm baboons.

Science.gov (United States)

Blanco, Cynthia L; McGill-Vargas, Lisa L; Gastaldelli, Amalia; Seidner, Steven R; McCurnin, Donald C; Leland, Michelle M; Anzueto, Diana G; Johnson, Marney C; Liang, Hanyu; DeFronzo, Ralph A; Musi, Nicolas

2015-03-01

Premature infants develop hyperglycemia shortly after birth, increasing their morbidity and death. Surviving infants have increased incidence of diabetes as young adults. Our understanding of the biological basis for the insulin resistance of prematurity and developmental regulation of glucose production remains fragmentary. The objective of this study was to examine maturational differences in insulin sensitivity and the insulin-signaling pathway in skeletal muscle and adipose tissue of 30 neonatal baboons using the euglycemic hyperinsulinemic clamp. Preterm baboons (67% gestation) had reduced peripheral insulin sensitivity shortly after birth (M value 12.5 ± 1.5 vs 21.8 ± 4.4 mg/kg · min in term baboons) and at 2 weeks of age (M value 12.8 ± 2.6 vs 16.3 ± 4.2, respectively). Insulin increased Akt phosphorylation, but these responses were significantly lower in preterm baboons during the first week of life (3.2-fold vs 9.8-fold). Preterm baboons had lower glucose transporter-1 protein content throughout the first 2 weeks of life (8%-12% of term). In preterm baboons, serum free fatty acids (FFAs) did not decrease in response to insulin, whereas FFAs decreased by greater than 80% in term baboons; the impaired suppression of FFAs in the preterm animals was paired with a decreased glucose transporter-4 protein content in adipose tissue. In conclusion, peripheral insulin resistance and impaired non-insulin-dependent glucose uptake play an important role in hyperglycemia of prematurity. Impaired insulin signaling (reduced Akt) contributes to the defect in insulin-stimulated glucose disposal. Counterregulatory hormones are not major contributors.

Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss

Directory of Open Access Journals (Sweden)

J. Schmitz

2016-05-01

Conclusions: These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as well as in a significant subpopulation of obese patients.

Effect of iodination site on binding of radiolabeled ligand by insulin antibodies and insulin autoantibodies

International Nuclear Information System (INIS)

Diaz, J.L.; Wilkin, T.J.

1988-01-01

Four human insulins and four porcine insulins, each monoiodinated to the same specific activity at one of the four tyrosine residues (A14, A19, B16, B26) and purified by reversed-phase liquid chromatography, were tested in a radiobinding assay against a panel of insulin-antibody (IA)-positive sera from 10 insulin-treated diabetics and insulin-autoantibody-positive (IAA) sera from 10 nondiabetics. Of the 10 IAA-positive sera, five were fully cross reactive with both insulin species, and five were specific for human insulin. The rank order of binding of sera with the four ligands from each species was random for IA (mean rank values of 1.9 for A14, 2.0 for A19, 2.5 for B16, and 3.6 for B26 from a possible ranking range of 1 to 4), but more consistent for non-human-insulin-specific IAA (mean rank values 1.3 for A14, 3.8 for A19, 1.7 for B16, and 3.2 for B26 for labeled human insulins; 1.2 for A14, 4.0 for A19, 1.8 for B16, and 3.0 for B26 for labeled porcine insulins). The rank order of binding was virtually uniform for human-insulin-specific IAA (mean values 1.2 for A14, 3.0 for A19, 1.8 for B16, and 4.0 for B26). The influence of iodination site on the binding of labeled insulin appears to be dependent on the proximity of the labeled tyrosine to the antibody binding site and the clonal diversity, or restriction, of insulin-binding antibodies in the test serum. When IA and IAA are measured, the implications of this study regarding the choice of assay ligand may be important

Effect of metabolic regulation on renal leakiness to dextran molecules in short-term insulin-dependent diabetics

DEFF Research Database (Denmark)

Parving, H H; Rutili, F; Granath, K

1979-01-01

Renal clearance of dextran of two ranges of molecular size and glomerular filtration rate (GFR, 51Cr-EDTA) were measured in seven short-term insulin-dependent diabetics (mean age 25 years). Measurements were carried out in the same patient during good and poor metabolic regulation (plasma glucose......, mean +/- SEM, 6.5 +/- 0.9 and 14.8 +/- 1.5 mmol/l, respectively). GFR was elevated in all patients during poor metabolic regulation (119 +/- 6 ml/min/1.73 m2, versus 99 +/- 2 ml/min/1.73 m2 during good control, p less than 0.01). The average renal clearance of dextran with molecular weights ranging...... from 25,000 to 35,000 and 35,000 to 45,000 increased during poor metabolic regulation from 14.8 +/- 0.8 to 19.8 +/- 1.8 ml/min/1.73 m2, and 5.2 +/- 0.3 to 6.8 +/- 0.6 ml/min/1.73 m2, respectively (p less than 0.05). The elevated GFR and renal dextran clearance found during poor metabolic regulation...

Complete loss of insulin secretion capacity in type 1A diabetes patients during long-term follow up.

Science.gov (United States)

Uno, Sae; Imagawa, Akihisa; Kozawa, Junji; Fukui, Kenji; Iwahashi, Hiromi; Shimomura, Iichiro

2017-10-16

Patients with type 1 diabetes are classified into three subtypes in Japan: acute onset, fulminant and slowly progressive. Acute-onset type 1 diabetes would be equivalent to type 1A diabetes, the typical type 1 diabetes in Western countries. The insulin secretion capacity in Japanese patients with long-standing type 1A diabetes is unclear. The aim of the present study was to clarify the course of endogenous insulin secretion during long-term follow up and the factors associated with residual insulin secretion in patients with acute-onset type 1 diabetes (autoimmune). We retrospectively investigated endogenous insulin secretion capacity in 71 patients who fulfilled the diagnostic criteria for acute-onset type 1 diabetes (autoimmune) in Japan. To assess the residual insulin secretion capacity, we evaluated randomly measured C-peptide levels and the results of glucagon stimulation test in 71 patients. In the first year of disease, the child- and adolescent-onset patients had significantly more in residual insulin secretion than the adult-onset patients (34 patients in total). C-peptide levels declined more rapidly in patients whose age of onset was ≤18 years than in patients whose age of onset was ≥19 years. Endogenous insulin secretion capacity stimulated by glucagon was completely lost in almost all patients at >15 years after onset (61 patients in total). Most patients with acute-onset type 1 diabetes (autoimmune) completely lose their endogenous insulin secretion capacity during the disease duration in Japan. Age of onset might affect the course of insulin secretion. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Dissociation between fat-induced in vivo insulin resistance and proximal insulin signaling in skeletal muscle in men at risk for type 2 diabetes

DEFF Research Database (Denmark)

Storgaard, Heidi; Jensen, Christine B; Björnholm, Marie

2004-01-01

The effect of short- (2 h) and long-term (24 h) low-grade Intralipid infusion on whole-body insulin action, cellular glucose metabolism, and proximal components of the insulin signal transduction cascade was studied in seven obese male glucose intolerant first degree relatives of type 2 diabetic...... h Intralipid infusion (0.4 ml.kg(-1).min(-1)). Insulin-stimulated glucose disposal decreased approximately 25% after short- and long-term fat infusion in both IGT relatives and controls. Glucose oxidation decreased and lipid oxidation increased after both short- and long-term fat infusion in both...... groups. Insulin-stimulated glucose oxidation was higher after long-term as compared with short-term fat infusion in control subjects. Short- or long-term infusion did not affect the absolute values of basal or insulin-stimulated insulin receptor substrate-1 tyrosine phosphorylation, tyrosine...

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Mumbai cohort of the A1chieve study.

Science.gov (United States)

Talwalkar, P G; Gupta, Vishal; Kovil, Rajiv

2013-11-01

The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Mumbai, India. A total of 2112 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 1561), insulin detemir (n = 313), insulin aspart (n = 144), basal insulin plus insulin aspart (n = 53) and other insulin combinations (n = 41). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 8.7%) and insulin user (mean HbA1c: 9.2%) groups. After 24 weeks of treatment, both the groups showed improvement in HbA1c (insulin naïve: -1.4%, insulin users: -1.8%). SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss.

Science.gov (United States)

Schmitz, J; Evers, N; Awazawa, M; Nicholls, H T; Brönneke, H S; Dietrich, A; Mauer, J; Blüher, M; Brüning, J C

2016-05-01

Obesity represents a major risk factor for the development of type 2 diabetes mellitus, atherosclerosis and certain cancer entities. Treatment of obesity is hindered by the long-term maintenance of initially reduced body weight, and it remains unclear whether all pathologies associated with obesity are fully reversible even upon successfully maintained weight loss. We compared high fat diet-fed, weight reduced and lean mice in terms of body weight development, adipose tissue and liver insulin sensitivity as well as inflammatory gene expression. Moreover, we assessed similar parameters in a human cohort before and after bariatric surgery. Compared to lean animals, mice that demonstrated successful weight reduction showed increased weight gain following exposure to ad libitum control diet. However, pair-feeding weight-reduced mice with lean controls efficiently stabilized body weight, indicating that hyperphagia was the predominant cause for the observed weight regain. Additionally, whereas glucose tolerance improved rapidly after weight loss, systemic insulin resistance was retained and ameliorated only upon prolonged pair-feeding. Weight loss enhanced insulin action and resolved pro-inflammatory gene expression exclusively in the liver, whereas visceral adipose tissue displayed no significant improvement of metabolic and inflammatory parameters compared to obese mice. Similarly, bariatric surgery in humans (n = 55) resulted in massive weight reduction, improved hepatic inflammation and systemic glucose homeostasis, while adipose tissue inflammation remained unaffected and adipocyte-autonomous insulin action only exhibit minor improvements in a subgroup of patients (42%). These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as

The effect of intensive insulin therapy on the insulin-regulatable glucose transporter (GLUT4) expression in skeletal muscle in type 1 diabetes

DEFF Research Database (Denmark)

Andersen, P H; Vestergaard, H; Lund, S

1993-01-01

h given to patients with Type 1 diabetes in poor metabolic control was associated with an adaptive regulation of GLUT4 mRNA and protein levels in vastus lateralis muscle. Nine Type 1 diabetic patients with a mean HbA1c of 10.3% were included in the protocol. After intensified treatment with soluble.......54). These results suggest, that in spite of evidence that high insulin levels affect GLUT4 expression in muscle, changes in serum insulin within the physiological range do not play a major role in the short-term regulation of GLUT4 expression in Type 1 diabetic patients....

Insulin Resistance and Prediabetes

Science.gov (United States)

... Your Baby is Born Monogenic Diabetes Insulin Resistance & Prediabetes Insulin resistance and prediabetes occur when your body ... will stay in the healthy range. What is prediabetes? Prediabetes means your blood glucose levels are higher ...

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Casablanca cohort of the A 1 chieve study

Directory of Open Access Journals (Sweden)

Ahmed Farouqi

2013-01-01

Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Casablanca, Morocco. Results: A total of 495 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 231, insulin detemir (n = 151, insulin aspart (n = 19, basal insulin plus insulin aspart (n = 53 and other insulin combinations (n = 41. At baseline glycaemic control was poor for both insulin naïve (mean HbA 1 c: 10.2% and insulin user (mean HbA 1 c: 9.4% groups. After 24 weeks of treatment, both groups showed improvement in HbA 1 c (insulin naïve: −2.3%, insulin users: −1.8%. Major hypoglycaemia was observed in the insulin naïve group after 24 weeks. SADRs were reported in 1.2% of insulin naïve and 2.1% of insulin user groups. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Short-term endurance training after coronary artery bypass grafting improves insulin resistance parameters in patients with hypertension.

Science.gov (United States)

Borowicz-Bieńkowska, Sławomira; Przywarska, Izabela; Dylewicz, Piotr; Pilaczyńska-Szcześniak, Łucja; Rychlewski, Tadeusz; Wilk, Małgorzata; Rózańska, Anna

2004-05-01

It has been shown that short-term exercise training improves insulin resistance parameters in patients with ischaemic heart disease. The effects of such a rehabilitation programme in patients with hypertension have not been well established. To assess whether short-term endurance training after coronary artery bypass grafting (CABG) may improve metabolic parameters and reduce blood pressure in patients with hypertension. The study group consisted of 30 male patients (15 with hypertension and 15 normotensive) aged 55+/-2.1 years who underwent CABG 1 to 6 months before the initiation of a 3-week endurance training. Glucose, insulin and C-peptide blood levels as well as binding and degradation of 125I-insulin by erythrocyte receptors were assessed before and after the training programme. The effects of training on blood pressure values were also evaluated. A significant improvement (phypertension. This was accompanied by a significant (phypertension, both the exercise systolic and diastolic pressures decreased significantly (pendurance training was especially effective in patients with hypertension in whom beneficial changes in some metabolic risk factors of ischaemic heart disease as well as the reduction in the blood pressure values were observed.

Comparing effects of insulin analogues and human insulin on nocturnal glycaemia in hypoglycaemia-prone people with Type 1 diabetes

DEFF Research Database (Denmark)

Kristensen, P. L.; Tarnow, L.; Bay, C.

2017-01-01

. Conclusions: Treatment with insulin analogue reduces the occurrence of nocturnal hypoglycaemia assessed by nocturnal glucose profiles in people with Type 1 diabetes prone to severe hypoglycaemia. Nocturnal glucose profiles provide a more comprehensive assessment of clinical benefit of insulin regimens......Aims: To assess the difference between analogue and human insulin with regard to nocturnal glucose profiles and risk of hypoglycaemia in people with recurrent severe hypoglycaemia. Methods: A total of 72 people [46 men, mean ± sd age 54 ± 12 years, mean ± sd HbA1c 65 ± 12 mmol/mol (8.1 ± 1.1......%), mean ± sd duration of diabetes 30 ± 14 years], who participated in a 2-year randomized, crossover trial of basal-bolus therapy with insulin detemir/insulin aspart or human NPH insulin/human regular insulin (the HypoAna trial) were studied for 2 nights during each treatment. Venous blood was drawn...

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Kolkata cohort of the A 1 chieve study

Directory of Open Access Journals (Sweden)

Anirban Majumder

2013-01-01

Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Kolkata, India. Results: A total of 576 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 417, insulin detemir (n = 70, insulin aspart (n = 55, basal insulin plus insulin aspart (n = 19 and other insulin combinations (n = 15. At baseline, glycaemic control was poor for both insulin naïve (mean HbA 1 c: 8.3% and insulin user (mean HbA 1 c: 8.6% groups. After 24 weeks of treatment, both the groups showed improvement in HbA 1 c (insulin naïve: −1.3%, insulin users: −1.4%. SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Short-term effects of replacing milk with cola beverages on insulin-like growth factor-I and insulin-glucose metabolism: a 10 d interventional study in young men.

Science.gov (United States)

Hoppe, Camilla; Kristensen, Mette; Boiesen, Marlene; Kudsk, Jane; Fleischer Michaelsen, Kim; Mølgaard, Christian

2009-10-01

In the Western world, a trend towards increased consumption of carbonated soft drinks combined with a decreasing intake of milk is observed. This may affect circulating insulin-like growth factor I (IGF-I) and fasting insulin, as seen in pre-pubertal children. The present study was designed to reflect the trend of replacing milk with carbonated beverages in young men and to study the effects of this replacement on IGF-I, IGF-binding protein 3 (IGFBP-3), IGF-I:IGFBP-3 and glucose-insulin metabolism. A randomised, controlled crossover intervention study, in which eleven men aged 22-29 years were given a low-Ca diet in two 10 d periods with 10 d washout in between. In one period, they drank 2.5 litres of Coca Cola(R) per day and the other period 2.5 litres of semi-skimmed milk. Serum IGF-I, IGFBP-3 (RIA), insulin (fluoro immunoassay) and glucose (Cobas) were determined at baseline and end point of each intervention period. Insulin resistance and beta-cell function were calculated with the homeostasis model assessment. A decrease in serum IGF-I was observed in the cola period compared with the milk period (P cola over a 10 d period decreases total IGF-I compared with a high intake of milk, with no effect on glucose-insulin metabolism in adult men. It is unknown whether this is a transient phenomenon or whether it has long-term consequences.

Intrauterine growth-restricted sheep fetuses exhibit smaller hindlimb muscle fibers and lower proportions of insulin-sensitive Type I fibers near term.

Science.gov (United States)

Yates, Dustin T; Cadaret, Caitlin N; Beede, Kristin A; Riley, Hannah E; Macko, Antoni R; Anderson, Miranda J; Camacho, Leticia E; Limesand, Sean W

2016-06-01

Intrauterine growth restriction (IUGR) reduces muscle mass and insulin sensitivity in offspring. Insulin sensitivity varies among muscle fiber types, with Type I fibers being most sensitive. Differences in fiber-type ratios are associated with insulin resistance in adults, and thus we hypothesized that near-term IUGR sheep fetuses exhibit reduced size and proportions of Type I fibers. Placental insufficiency-induced IUGR fetuses were ∼54% smaller (P fetal muscles develop smaller fibers and have proportionally fewer Type I fibers, which is indicative of developmental adaptations that may help explain the link between IUGR and adulthood insulin resistance. Copyright © 2016 the American Physiological Society.

Postreceptor defects causing insulin resistance in normoinsulinemic non-insulin-dependent diabetes mellitus

International Nuclear Information System (INIS)

Bolinder, J.; Ostman, J.; Arner, P.

1982-01-01

The mechanisms of the diminished hypoglycemic response to insulin in non-insulin-dependent diabetes mellitus (NIDDM) with normal levels of circulating plasma insulin were investigated. Specific binding of mono- 125 I (Tyr A14)-insulin to isolated adipocytes and effects of insulin (5--10,000 microunits/ml) on glucose oxidation and lipolysis were determined simultaneously in subcutaneous adipose tissue of seven healthy subjects of normal weight and seven untreated NIDDM patients with normal plasma insulin levels. The two groups were matched for age, sex, and body weight. Insulin binding, measured in terms of receptor number and affinity, was normal in NIDDM, the total number of receptors averaging 350,000 per cell. Neither sensitivity nor the maximum antilipolytic effect of insulin was altered in NIDDM patients as compared with control subjects; the insulin concentration producing half the maximum effect (ED50) was 10 microunits/ml. As regards the effect of insulin on glucose oxidation, for the control subjects ED50 was 30 microunits/ml, whereas in NIDDM patients, insulin exerted no stimulatory effect. The results obtained suggest that the effect of insulin on glucose utilization in normoinsulinemic NIDDM may be diminished in spite of normal insulin binding to receptors. The resistance may be due solely to postreceptor defects, and does not involve antilipolysis

Short-term antidiabetic treatment with insulin or metformin has a similar impact on the components of metabolic syndrome in women with gestational diabetes mellitus requiring antidiabetic agents: results of a prospective, randomised study.

Science.gov (United States)

Zawiejska, A; Wender-Ozegowska, E; Grewling-Szmit, K; Brazert, M; Brazert, J

2016-04-01

Gestational diabetes mellitus (GDM) is associated with an increased prevalence of fetal and maternal complications primarily caused by maternal hyperglycemia, which results in abnormal fetal growth. Diet modification is a common first step in the treatment of GDM, followed by antidiabetic pharmacotherapy if this approach fails. Insulin therapy is generally accepted; however, oral hypoglycemic agents have been used in this population. In this prospective, randomised study, we compared maternal metabolic status after treatment with insulin or metformin. Pregnant women (gestational age: ≥ 20 weeks) with GDM requiring medical hypoglycemic treatment were randomly allocated to the Metformin (n = 35) or Insulin (n = 43) Groups. Maternal metabolic status - assessed by glycated hemoglobin (HBA1c) level, glycemic profile, insulin concentration, Homeostatic Model Assessment - Insulin Resistance index, and lipids - was recorded at booking and throughout pregnancy. The characteristics of the study group were: maternal age 33.5 ± 5.9 years, gestational age at baseline 28.5 ± 3.5 weeks, prepregnancy body mass index (BMI) 32.2 ± 3.5 kg/m(2), HbA1c at baseline 5.6 ± 0.6%, and average daily glycemia 5.9 ± 0.6 mmol/dl. Fasting glycemia at term was significantly lower in the Insulin Group but there were no significant differences in mean daily glycemia, HbA1c and BMI at term between the groups. Longitudinally, there was a small but significant increase in BMI and a significant increase in high-density lipoprotein-cholesterol in the Insulin Group and a significant increase in the atherogenic index of plasma (AIP) and a trend towards higher triglycerides in the Metformin Group. Both fasting and average daily glycemia were significantly reduced following treatment in both groups. No such change was evident for HbA1c. In a relative risk analysis, metformin treatment was associated with an insignificant elevated risk of HbA1c, triglycerides and lipid indices falling within the

Insulin aspart pharmacokinetics

DEFF Research Database (Denmark)

Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin

2014-01-01

Background: Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control postprandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between...... to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic...... distribution and elimination (Porksen et al., 1997; Sjostrand et al., 2002). PK and PD profiles for type 1 diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir et al. (2009) and Ma et al. (2012b...

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Northern Tunisia cohort of the A1chieve study

Science.gov (United States)

Blouza, Samira; Jamoussi, Henda

2013-01-01

Background: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Northern Tunisia. Results: A total of 443 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 137), insulin detemir (n = 243), insulin aspart (n = 11), basal insulin plus insulin aspart (n = 39) and other insulin combinations (n = 13). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 10.2%) and insulin user (mean HbA1c: 9.8%) groups. After 24 weeks of treatment, both the study groups showed improvement in HbA1c (insulin naïve: −2.1%, insulin users: −0.9%). SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia. PMID:24404473

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Northern Tunisia cohort of the A 1 chieve study

Directory of Open Access Journals (Sweden)

Samira Blouza

2013-01-01

Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Northern Tunisia. Results: A total of 443 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 137, insulin detemir (n = 243, insulin aspart (n = 11, basal insulin plus insulin aspart (n = 39 and other insulin combinations (n = 13. At baseline glycaemic control was poor for both insulin naïve (mean HbA 1 c: 10.2% and insulin user (mean HbA 1 c: 9.8% groups. After 24 weeks of treatment, both the study groups showed improvement in HbA 1 c (insulin naïve: −2.1%, insulin users: −0.9%. SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Insulin production rate in normal man as an estimate for calibration of continuous intravenous insulin infusion in insulin-dependent diabetic patients.

Science.gov (United States)

Waldhäusl, W K; Bratusch-Marrain, P R; Francesconi, M; Nowotny, P; Kiss, A

1982-01-01

This study examines the feasibility of deriving the 24-h insulin requirement of insulin-dependent diabetic patients who were devoid of any endogenous insulin release (IDD) from the insulin-production rate (IPR) of healthy man (basal, 17 mU/min; stimulated 1.35 U/12.5 g glucose). To this end, continuous intravenous insulin infusion (CIVII) was initiated at a precalculated rate of 41.2 +/- 4.6 (SD) U/24 h in IDD (N - 12). Blood glucose profiles were compared with those obtained during intermittent subcutaneous (s.c.) insulin therapy (IIT) and those of healthy controls (N = 7). Regular insulin (Hoechst CS) was infused with an adapted Mill Hill Infuser at a basal infusion rate of 1.6 U/h (6:00 a.m. to 8:00 p.m.), and of 0.8 U/h from 8:00 p.m. to 6:00 a.m. Preprandial insulin (3.2-6.4 U) was added for breakfast, lunch, and dinner. Daily individual food intake totaled 7688 +/- 784 kJ (1836 +/- 187 kcal)/24 h including 184 +/- 37 g of glucose. Proper control of blood glucose (BG) (mean BG 105 +/- 10 mg/dl; mean amplitude of glycemic excursions 54 +/- 18 mg/dl; and 1 h postprandial BG levels not exceeding 160 mg/dl) and of plasma concentrations of beta-hydroxybutyrate and lactate was maintained by 41.4 +/- 4.4 U insulin/24 h. Although BG values only approximated the upper normal range as seen in healthy controls, they were well within the range reported by others during CIVII. Therefore, we conclude that in adult IDD completely devoid of endogenous insulin (1) the IPR of normal man can be used during CIVII as an estimate for the patient's minimal insulin requirement per 24 h, and (2) this approach allows for a blood glucose profile close to the upper range of a normal control group. Thus, deriving a patient's daily insulin dose from the insulin production rate of healthy man may add an additional experimental protocol which aids in making general calculations of a necessary insulin dose instead of using trial and error or a closed-loop insulin infusion system.

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Rajasthan cohort of the A 1 chieve study

Directory of Open Access Journals (Sweden)

Akhil Joshi

2013-01-01

Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Rajasthan, India. Results: A total of 477 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 340, insulin detemir (n = 90, insulin aspart (n = 37, basal insulin plus insulin aspart (n = 7 and other insulin combinations (n = 2. At baseline glycaemic control was poor for both insulin naïve (mean HbA 1 c: 8.3% and insulin user (mean HbA 1 c: 8.4% groups. After 24 weeks of treatment, both the groups showed improvement in HbA 1 c (insulin naïve: −0.9%, insulin users: −1.2%. Major hypoglycaemic events decreased from 0.5 events/patient-year to 0.0 events/patient-year in insulin naïve group while no change from baseline (1.3 events/patients-year was observed for insulin users. SADRs were not reported in any of the study patients. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Glucose-stimulated insulin response in pregnant sheep following acute suppression of plasma non-esterified fatty acid concentrations

Directory of Open Access Journals (Sweden)

Sriskandarajah Nadarajah

2004-09-01

Full Text Available Abstract Background Elevated non-esterified fatty acids (NEFA concentrations in non-pregnant animals have been reported to decrease pancreatic responsiveness. As ovine gestation advances, maternal insulin concentrations fall and NEFA concentrations increase. Experiments were designed to examine if the pregnancy-associated rise in NEFA concentration is associated with a reduced pancreatic sensitivity to glucose in vivo. We investigated the possible relationship of NEFA concentrations in regulating maternal insulin concentrations during ovine pregnancy at three physiological states, non-pregnant, non-lactating (NPNL, 105 and 135 days gestational age (dGA, term 147+/- 3 days. Methods The plasma concentrations of insulin, growth hormone (GH and ovine placental lactogen (oPL were determined by double antibody radioimmunoassay. Insulin responsiveness to glucose was measured using bolus injection and hyperglycaemic clamp techniques in 15 non-pregnant, non-lactating ewes and in nine pregnant ewes at 105 dGA and near term at 135 dGA. Plasma samples were also collected for hormone determination. In addition to bolus injection glucose and insulin Area Under Curve calculations, the Mean Plasma Glucose Increment, Glucose Infusion Rate and Mean Plasma Insulin Increment and Area Under Curve were determined for the hyperglycaemic clamp procedures. Statistical analysis of data was conducted with Students t-tests, repeated measures ANOVA and 2-way ANOVA. Results Maternal growth hormone, placental lactogen and NEFA concentrations increased, while basal glucose and insulin concentrations declined with advancing gestation. At 135 dGA following bolus glucose injections, peak insulin concentrations and insulin area under curve (AUC profiles were significantly reduced in pregnant ewes compared with NPNL control ewes (p Conclusions Results suggest that despite an acute suppression of circulating NEFA concentrations during pregnancy, the associated steroids and hormones

Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

Science.gov (United States)

Richey, Joyce M.; Castro, Ana Valeria B.; Broussard, Josiane L.; Ionut, Viorica; Bergman, Richard N.

2015-01-01

Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance. PMID:25852002

The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults

DEFF Research Database (Denmark)

Rosenfalck, A M; Maghsoudi, S; Fisker, S

2000-01-01

The aim of the present study was to evaluate the long-term (30 months) metabolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 microg/kg x day (= 1.6 IU/day), in 11 patients with adult GH deficiency. Glucose metabolism was evaluated by an oral glucose tolerance test and an iv...... (frequently sampled iv glucose tolerance test) glucose tolerance test, and body composition was estimated by dual-energy x-ray absorptiometry. Treatment with rhGH induced persistent favorable changes in body composition, with a 10% increase in lean body mass (P ... in glucose tolerance, beta-cell response was still inappropriate. Our conclusion is that long-term rhGH-replacement therapy in GH deficiency adults induced a significant deterioration in glucose tolerance, profound changes in kinetics of C-peptide, and insulin and prehepatic insulin secretion, despite...

Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics

OpenAIRE

Pozzilli, Paolo; Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz?Chobot, Przemyslawa; Renard, Eric

2015-01-01

Summary The level of glycaemic control necessary to achieve optimal short?term and long?term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid?acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion ...

[Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy].

Science.gov (United States)

Pesić, Milica; Zivić, Sasa; Radenković, Sasa; Velojić, Milena; Dimić, Dragan; Antić, Slobodan

2007-04-01

Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05). Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Insulin sensitivity and albuminuria

DEFF Research Database (Denmark)

Pilz, Stefan; Rutters, Femke; Nijpels, Giel

2014-01-01

OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

Sodium retention and insulin treatment in insulin-dependent diabetes mellitus

DEFF Research Database (Denmark)

Nørgaard, K; Feldt-Rasmussen, B

1994-01-01

subcutaneously, contributes to the increased ENa. Three studies were performed. Study 1 was a cross-sectional study comprising 28 type 1 diabetic men (aged 18-35 years) with short-duration diabetes (diabetic complications, and 22 control subjects. Study 2 was a prospective study of 17...... subcutaneous insulin infusion for improvement of glycaemic control or to remain on conventional insulin treatment. In study 1, ENa was higher in short-duration type 1 diabetic men than in controls (3003 +/- 325 vs 2849 +/- 207 mEq/1.73 m2, P ...The hypothesis that total body exchangeable sodium (ENa) is elevated in type 1 (insulin-dependent) diabetic patients with short-duration diabetes and no signs of microangiopathy was tested. Also tested was whether peripheral hyperinsulinaemia, in terms of the amounts of insulin injected...

Insulin use, prescription patterns, regimens and costs.-a narrative from a developing country

Directory of Open Access Journals (Sweden)

Ogbera Anthonia O

2012-12-01

Full Text Available Abstract Background Achieving good glycemic control is of paramount importance in the reduction of diabetes mellitus (DM associated morbidity and mortality. Insulin plays a key role in the management of DM but unfortunately whilst some healthcare providers present insulin as a treatment of last resort , patients on insulin often have insulin related issues such as needle phobias, fear of hypoglycaemia, weight gain and in developing countries, costs. This Report aims at assessing insulin prescription pattern, insulin costs and issues associated with adherence. Methods This was a Cross-sectional observation Study whereby 160 patients with DM who were on insulin solely or in combination with oral hypoglycaemic agents were recruited over a 6 month period. Information obtained from the Study subjects pertained to their histories of DM, types of insulin, insulin costs, adherence issues and insulin delivery devices. Long and short term glycaemic control were determined and evaluated for possible relation to insulin adherence. Test statistics used were chi square, t test and binary regression. Results Insulin adherence was noted in 123-77% of the Study subjects and this was comparable between persons with type 1 DM and those with type 2 DM. The mean glycosylated haemoglobin values were significantly higher in those who admitted to non insulin adherence compared to those who adhered to their insulin regimen (9.7% (2.3 Vs 8.6% (2.1, p = 0.01. Reasons proffered by Respondents for non insulin adherence included high costs-15(41%, inconvenience −15 (41% and needle pain-7918%. A greater proportion of persons who self injected insulin adhered to insulin prescriptions compared to those who did not self inject and thus had better glycaemic control. Shorter duration of DM and older age were found to be predictors of adherence to insulin prescription. The monthly mean costs of insulin for those who earned an income was 5212.8 Nigerian naira which is

[News and perspectives in insulin treatment].

Science.gov (United States)

Haluzík, Martin

2014-09-01

Insulin therapy is a therapeutic cornerstone in patients with type 1 diabetes and also in numerous patients with type 2 diabetes especially with longer history of diabetes. The initiation of insulin therapy in type 2 diabetes patients is often delayed which is at least partially due to suboptimal pharmacokinetic characteristics of available insulins. The development of novel insulins with more favorable characteristics than those of current insulins is therefore still ongoing. The aim of this paper is to review current knowledge of novel insulins that have been recently introduced to the market or are getting close to routine clinical use. We will also focus on the perspectives of insulin therapy in the long-term run including the alternative routes of insulin administration beyond its classical subcutaneous injection treatment.Key words: alternative routes of insulin administration - diabetes mellitus - hypoglycemia - insulin - insulin analogues.

Comparison of insulin analogue B9AspB27Glu and soluble human insulin in insulin-treated diabetes.

Science.gov (United States)

Kang, S; Owens, D R; Vora, J P; Brange, J

1990-02-10

Postprandial plasma glucose excursions and plasma levels of free insulin after subcutaneous bolus injection of a rapidly absorbed monomeric insulin analogue (B9AspB27Glu) or soluble human insulin ('Actrapid HM' U100) were studied in six insulin-treated diabetic subjects. 10 U actrapid or an equimolar amount of the analogue were injected, in random order with an interval of 1 week, immediately before a 500 kcal test meal. Basal insulin levels were similar on the 2 study days (mean 74.1 [SE 5.1] pmol/l, actrapid; 79.7 [13.0] pmol/l, analogue). After injection of actrapid plasma free insulin levels rose slowly, reaching a plateau by 105 min at 222 (19) pmol/l. Injection of the analogue resulted in a rapid early peak at 30 min (798 [112] pmol/l), and levels were significantly higher than those after actrapid between 15 and 210 min. The more physiological plasma insulin levels achieved with the analogue were accompanied by a substantial reduction in postprandial plasma glucose excursions; the integrated area under the incremental plasma glucose curve was 45% lower after the analogue than after actrapid.

The effect of tubing dwell time on insulin adsorption during intravenous insulin infusions.

Science.gov (United States)

Thompson, Cecilia D; Vital-Carona, Jessica; Faustino, E Vincent S

2012-10-01

Insulin adsorbs to plastic tubing, which decreases the concentration of an insulin solution delivered from an intravenous infusion set. Dwelling insulin within tubing before starting the infusion decreases adsorption but delays treatment initiation and wastes time in infusion preparation. The lack of data on dwell time effects results in wide variability in practice. We aim to determine the effect of dwell time on insulin concentration from intravenous infusion tubing. In this in vitro study, we used insulin solutions with concentrations of 0.1 unit/mL, 1 unit/mL, and 10 units/mL. Each solution dwelled in intravenous infusion sets for 0, 15, 30, or 60 min. After the dwell, we measured insulin concentrations from the solution bags and tubing. We repeated each insulin concentration-dwell time combination five times. Comparisons were performed using analyses of variance. For each of the three insulin concentrations, the mean insulin concentrations from the tubing were not significantly different between dwell times. Duration of dwell time did not affect insulin adsorption in polypropylene intravenous infusion sets. We recommend that following a 20-mL flush, insulin infusions can be started without any dwell time. Removal of dwell times may improve clinical practice by minimizing preparation time and will allow faster initiation of insulin infusion therapy.

Comparing the quality of life in insulin recipient and refusal patients with type 2 diabetes.

Science.gov (United States)

Khalili, Mitra; Sabouhi, Fakhri; Abazari, Parvaneh; Aminorroaya, Ashraf

2016-01-01

Better control of blood sugar and reduction of diabetes complications through insulin therapy could convince people to choose this method. However, patients might refuse insulin therapy due to its painful injection, limitations in daily activities, and hypoglycemia. Thus, insulin therapy could have both positive and negative effects on patients' quality of life (QOL). Therefore, the aim of this study was to compare the QOL of insulin recipient and insulin refusal patients with type 2 diabetes. This study was a descriptive and comparative research conducted on 126 patients; 63 were insulin recipients and 63 had refused insulin therapy. Participants were under the care of the Endocrine and Metabolism Research Center of Isfahan, Iran. Data were gathered using the Diabetes Quality of Life (DQOL) questionnaire. In this tool, higher scores indicated lower QOL in patients. Data were analyzed using independent t-test, analysis of covariance, Mann-Whitney, Chi-square, and Pearson and Spearman's correlation. There was a significant difference (P refusal patients (mean = 1.74, SD = 0.41) in terms of mean QOL score. In addition, men and participants with higher educational levels reported a better QOL (P refusal patients had a better QOL. It seems that QOL is associated with the acceptance or refusal of insulin therapy. Therefore, enhancement of QOL could be related to all aspects of the disease, especially its treatment method and solving the therapeutic problems.

Toward understanding insulin fibrillation.

Science.gov (United States)

Brange, J; Andersen, L; Laursen, E D; Meyn, G; Rasmussen, E

1997-05-01

Formation of insulin fibrils is a physical process by which partially unfolded insulin molecules interact with each other to form linear aggregates. Shielding of hydrophobic domains is the main driving force for this process, but formation of intermolecular beta-sheet may further stabilize the fibrillar structure. Conformational displacement of the B-chain C-terminal with exposure of nonpolar, aliphatic core residues, including A2, A3, B11, and B15, plays a crucial role in the fibrillation process. Recent crystal analyses and molecular modeling studies have suggested that when insulin fibrillates this exposed domain interacts with a hydrophobic surface domain formed by the aliphatic residues A13, B6, B14, B17, and B18, normally buried when three insulin dimers form a hexamer. In rabbit immunization experiments, insulin fibrils did not elicit an increased immune response with respect to formation of IgG insulin antibodies when compared with native insulin. In contrast, the IgE response increased with increasing content of insulin in fibrillar form. Strategies and practical approaches to prevent insulin from forming fibrils are reviewed. Stabilization of the insulin hexameric structure and blockage of hydrophobic interfaces by addition of surfactants are the most effective means of counteracting insulin fibrillation.

Determination of 24-hour insulin infusion pattern by an artificial endocrine pancreas for intravenous insulin infusion with a miniature pump

DEFF Research Database (Denmark)

Kølendorf, K; Christiansen, J S; Bojsen, J

1981-01-01

UNLABELLED: Intravenous insulin infusion with a glucose controlled insulin infusion system (GCIIS) is known to restore glucose homeostasis. A simpler approach to improve blood glucose regulation is preprogrammed intravenous insulin infusion with portable pumps without sensor-mediated feedback. We...... report a study designed to evaluate whether the preprogrammed insulin infusion pattern to be used in the miniature insulin infusion pump (MIIP) could be optimized by concomitant employment of the GCIIS for blood glucose control. Six juvenile-onset insulin-dependent diabetics (mean age 31 yrs) were...... studied. Mean blood glucose (MBG) was 6.2 mmol/l +/- 0.5 (SD) during glucose controlled infusion and 5.3 +/- 0.6 during the combined MIIP + GCIIS-day. The insulin requirements calculated from the s.c. regimen (56 U +/- 10 SD) were identical to the GCIIS-measured (51 U +/- 14) and to the amounts delivered...

Psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin.

Science.gov (United States)

Petrak, Frank; Herpertz, Stephan; Stridde, Elmar; Pfützner, Andreas

2013-08-01

"Psychological insulin resistance" (PIR) is an obstacle to insulin treatment in type 2 diabetes, and patients' expectations regarding alternative ways of insulin delivery are poorly understood. PIR and beliefs regarding treatment alternatives were analyzed in patients with type 2 diabetes (n=532; mean glycated hemoglobin, 68±12 mmol/mol [8.34±1.5%]) comparing oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin. Questionnaires were used to assess barriers to insulin treatment (BIT), generic and diabetes-specific quality of life (Short Form 36 and Problem Areas in Diabetes, German version), diabetes knowledge, locus of control (Questionnaire for the Assessment of Diabetes-Specific Locus of Control, in German), coping styles (Freiburg Questionnaire of Illness Coping, 15-Items Short Form), self-esteem (Rosenberg Self-Esteem Scale, German version), and mental disorders (Patient Health Questionnaire, German version). Patients discussed treatment optimization options with a physician and were asked to make a choice about future diabetes therapy options in a two-step treatment choice scenario. Step 1 included oral antidiabetes drugs or subcutaneous insulin injection (SCI). Step 2 included an additional treatment alternative of inhaled insulin (INH). Subgroups were analyzed according to their treatment choice. Most patients perceived their own diabetes-related behavior as active, problem-focused, internally controlled, and oriented toward their doctors' recommendations, although their diabetes knowledge was limited. In Step 1, rejection of the recommended insulin was 82%, and in Step 2, it was 57%. Fear of hypoglycemia was the most important barrier to insulin treatment. Patients choosing INH (versus SCI) scored higher regarding fear of injection, expected hardship from insulin therapy, and BIT-Sumscore. The acceptance of insulin is very low in type 2 diabetes patients. The option to inhale insulin increases the acceptability for some but

Homeostatic model assessment for insulin resistance (homa-ir): a better marker for evaluating insulin resistance than fasting insulin in women with polycystic ovarian syndrome

International Nuclear Information System (INIS)

Majid, H.; Khan, A.H.; Masood, Q.

2017-01-01

To assess the utility of HOMA-IR in assessing insulin resistance in patients with polycystic ovary syndrome (PCOS) and compare it with fasting insulin for assessing insulin resistance (IR). Study Design: Observational study. Place and Duration of Study: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2009 to September 2012. Methodology: Medical chart review of all women diagnosed with PCOS was performed. Of the 400 PCOS women reviewed, 91 met the inclusion criteria. Insulin resistance was assessed by calculating HOMA-IR using the formula (fasting glucose x fasting insulin)/405, taking normal value =12 micro IU/ml. Results: A total of 91 premenopausal women diagnosed with PCOS were included. Mean age was 30 +-5.5 years. Mean HOMA-IR of women was 3.1 +-1.7, respectively with IR in 69% (n=63) women, while hyperinsulinemia was present in 60% (n=55) women (fasting Insulin 18.5 +-5.8 micro IU/ml). Hyperandrogenism was present in 53.8% (n=49), whereas 38.5% (n=35) women had primary infertility or subfertility, while 65.9% (n=60) had menstrual irregularities; and higher frequencies were observed in women with IR. Eight subjects with IR and endocrine abnormalities were missed by fasting insulin. Conclusion: Insulin resistance is common in PCOS and it is likely a pathogenic factor for development of PCOS. HOMA-IR model performed better than hyperinsulinemia alone for diagnosing IR. (author)

Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy

Directory of Open Access Journals (Sweden)

Pešić Milica

2007-01-01

Full Text Available Background/Aim. Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin for basal insulin supply in patients with type 1 diabetes. Methods. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IIT were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15; 2. NPH insulin twice daily (n = 15; 3. insulin glargine once daily (n = 18. Meal time insulin aspart was continued in all groups. Results. Fasting blood glucose (FBG was lower in the glargine group (7.30±0.98 mmol/l than in the twice daily NPH group (7.47±1.06 mmol/l, but without significant difference. FBG was significantly higher in the once daily NPH group (8.44±0.85 mmol/l; p < 0.05. HbA1c after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72±0.86% to 6.87±0.50%, as well as in the twice daily NPH group (from 7.80±0.83% to 7.01±0.63%. Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56±2.09 than in both NPH groups (9.0±1.65 in twice daily NPH group and 8.13±1.30 in other NPH group (episodes/patients-month, p < 0.05. Conclusion. Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbA1c and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Insulin-Like Growth Factor-1 Levels in Term Newborns with Hypoxic-Ischemic Encephalopathy.

Science.gov (United States)

Umran, Raid M R; Al-Tahir, Mahir; Jagdish, Desai; Chouthai, Nitin

2016-06-01

Objective This study aims to evaluate the correlation of changes in serum insulin-like growth factor-1 (IGF-1) levels with the clinical staging of hypoxic-ischemic encephalopathy (HIE) in term newborns. Study Design A prospective study of 29 newborns with HIE (stage I = 15, stage II + III = 14) and 28 healthy term newborns as the control group was performed in the neonatal intensive care unit. IGF-1 levels were obtained within 6 hours after birth from HIE and control groups and again on day 3 from HIE group. HIE was classified using the Sarnat staging I to III. Results IGF-1 levels were significantly lower in the HIE group than in the control group (p = 0.024). It was lower in the HIE stage II to III group compared with HIE stage I group at birth (p < 0.0001) and on day 3 (p = 0.009). The mean IGF-1 levels were significantly higher on day 3 than on day 1 among stage II to III HIE (p = 0.006) and it was inversely correlated with staging (R =  - 0.475, p = 0.009). There was a significant correlation between IGF-1 levels and Apgar score at 5 (R = 0.39, p = 0.042) and 10 minutes (R = 0.38, p = 0.035). Conclusions IGF-1 was lower in HIE and inversely correlated with clinical staging. It was increased with clinical improvement in the subsequent days. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Association of mean platelet volume with androgens and insulin resistance in nonobese patients with polycystic ovary syndrome.

Science.gov (United States)

Dogan, Bercem Aycicek; Arduc, Ayse; Tuna, Mazhar Muslum; Karakılıc, Ersen; Dagdelen, Iffet; Tutuncu, Yasemin; Berker, Dilek; Guler, Serdar

2014-10-01

Mean platelet volume (MPV) is generally accepted as a new marker of cardiovascular disease risk in several studies. This study aimed to determine the association of MPV with androgen hormones and insulin resistance (IR) in nonobese patients with polycystic ovary syndrome (PCOS). A total of 136 patients with newly diagnosed reproductive-age PCOS (regarding the criteria of new PCOS phenotypes, based on the Rotterdam criteria) who were nonobese with the mean age of 25 years (25.39 ± 5.51) and mean body mass index (BMI) of 21 kg/m(2) (22.07 ± 2.13) were included. In addition, 59 healthy subjects with mean age of 26 years (22.07 ± 2.13) and mean BMI of 22 kg/m(2) (21.52 ± 3.84) were recruited as control. Total blood count (including MPV), total testosterone, free testosterone, dehydroepiandrosterone-sulfate (DHEAS), and androstenedione levels were recorded. IR was calculated from blood chemistry measurements of fasting insulin and glucose according to updated homeostasis model assessment. No differences were observed in mean MPV values between patients and control group (9.02 fL (8.5-10.1) and 8.9 fL (7.7-9.1), respectively; P = 0.777). MPV values were similar among nonobese patients with and without IR and control subjects (P > 0.05). We detected significantly lower values of MPV in patients with hyperandrogenemia in comparison to patients with normal androgen levels (8.7 and 9.5 fL, P = 0.012). There was a negative correlation between total testosterone, DHEAS, and MPV (P = 0.016, r = -0.229; and P = 0.006, r = -0.261, respectively). Multiple logistic regression analyses confirmed the independence of these associations. Our study revealed that nonobese women with and without PCOS have similar MPV values. While IR does not have any effect on MPV, elevated androgen levels are associated with a low MPV in nonobese patients with PCOS.

Determination of Insulin Resistance and Beta Cell Function in Healthy Obese and Non-obese Individuals

International Nuclear Information System (INIS)

Kazmi, A.; Sattar, A.; Tariq, K. M.; Najamussahar; Hashim, R.; Almani, M. I.

2013-01-01

Objective: To determine insulin resistance and beta cell function in healthy obese and nonobese individuals of the local population. Study Design: Case control study. Place and Duration of Study: AFIP Rawalpindi in collaboration with department of medicine military hospital(MH) Rawalpindi, from Aug 2008 to Mar 2009. Methods: Eighty obese(n=40) and non-obese(n=40) subjects were selected by non-probability convenience sampling. Plasma insulin, glucose, and serum total cholestrol were estimated in fasting state. Insulin resistance was calculated by HOMA-IR and beta cell function by HOMA- equation. Results: Significant differences were observed between obese and non-obese individuals regarding insulin resistance, beta cell function, and BMI and serum total cholesterol. Mean insulin resistance in obese group was found to be 11.1 +- 5.1(range 7.0-16.2) and in non-obese group it was 0.9+-0.4 (range 0.5-1.3). This difference was highly significant (p=0.001). There was a highly significant difference between the two groups in term of beta cell function with mean rank 60.1 for obese group and 20.9 non obese groups (Asym sig. 2 tailed 0.000). Also the correlation (r = 0.064) between insulin resistance and beta cell function in obese group is highly significant (p = 0.000). Mean serum leptin levels were lower (6.3 ng/ml) in non-obese, and high (57.2 ng/ml) in the obese group. Conclusions: Insulin resistance is found higher in obese individuals. Beta cell function is significantly different between obese and non-obese groups. (author)

On the labelling of insuline and insuline derivatives with tritium and carbon-14

International Nuclear Information System (INIS)

Uschkoreit, J.

1979-01-01

Two different labelling methods were investigated. By means of the Wilzbach labelling with diaminosuberoylinsuline the insuline is irreversibly altered. As a second method the reductive methylation was used, in doing so it was possible to distinguish between mono and dimethylated parts of the reaction product by using C-14 labelled formaldehyde. Furthermore four N,N-dimethylated insuline derivatives were isolated with yields of 25 until 35%. By using C-14 and h-3 labelled reagents insuline can be labelled doubly. Moreover N-terminal amino groups could be protected irreversibly with this method. Furthermore structure-function investigations and investigations concerning the insuline metabolism were done. (SPI) [de

Insulin dependence and pancreatic enzyme replacement therapy are independent prognostic factors for long-term survival after operation for chronic pancreatitis.

Science.gov (United States)

Winny, Markus; Paroglou, Vagia; Bektas, Hüseyin; Kaltenborn, Alexander; Reichert, Benedikt; Zachau, Lea; Kleine, Moritz; Klempnauer, Jürgen; Schrem, Harald

2014-02-01

This retrospective, single-center, observational study on postoperative long-term results aims to define yet unknown factors for long-term outcome after operation for chronic pancreatitis. We analyzed 147 consecutive patients operated for chronic pancreatitis from 2000 to 2011. Mean follow-up was 5.3 years (range, 1 month to 12.7 years). Complete long-term survival data were provided by the German citizen registration authorities for all patients. A quality-of-life questionnaire was sent to surviving patients after a mean follow-up of 5.7 years. Surgical principles were resection (n = 86; 59%), decompression (n = 29; 20%), and hybrid procedures (n = 32; 21%). No significant influences of different surgical principles and operative procedures on survival, long-term quality of life and pain control could be detected. Overall 30-day mortality was 2.7%, 1-year survival 95.9%, and 3-year survival 90.8%. Multivariate Cox regression analysis revealed that only postoperative insulin dependence at the time of hospital discharge (P = .027; Exp(B) = 2.111; 95% confidence interval [CI], 1.089-4.090) and the absence of pancreas enzyme replacement therapy at the time of hospital discharge (P = .039; Exp(B) = 2.102; 95% CI, 1.037-4.262) were significant, independent risk factors for survival with significant hazard ratios for long-term survival. Long-term improvement in quality of life was reported by 55 of 76 long-term survivors (73%). Pancreatic enzyme replacement should be standard treatment after surgery for chronic pancreatitis at the time of hospital discharge, even when no clinical signs of exocrine pancreatic failure exist. This study underlines the potential importance of early operative intervention in chronic pancreatitis before irreversible endocrine dysfunction is present. Copyright © 2014 Mosby, Inc. All rights reserved.

Insulin resistance, exercise capacity and body composition in subjects with two hypertensive parents

DEFF Research Database (Denmark)

Andersen, U B; Dige-Petersen, H; Ibsen, H

1999-01-01

OBJECTIVE: To study insulin resistance in subjects with strong genetic predisposition to essential hypertension, compared with non-disposed subjects. SUBJECTS: Thirty normotensive subjects aged 18-35 years whose parents both had essential hypertension, and 30 age- and sex matched subjects whose...... correlated to abdominal fat mass but not to insulin sensitivity. CONCLUSION: Subjects with a strong genetic predisposition to essential hypertension had increased diastolic blood pressure compared with subjects with normotensive parents, but they were not insulin resistant. This may be due to the subjects...... for the difference between the means; -0.5; -7.9), but the insulin sensitivity index was similar: 312 versus 362 I(2) min(-1) pmol(-1) kg(-1) (28; -129). The two groups were similar in terms of body composition, exercise capacity and composition of usual diet. Resting and 24-h diastolic blood pressures were...

Insulin degludec as an ultralong-acting basal insulin once a day: a systematic review

Directory of Open Access Journals (Sweden)

Wang F

2012-07-01

Full Text Available Fei Wang,1 Justine Surh,1 Manmeet Kaur21University of Connecticut School of Pharmacy, Department of Pharmacy Practice, Storrs, 2Joslin Diabetes Center Affiliate, Hospital of Central Connecticut, New Britain, CT, USABackground: Insulin degludec (IDeg is a neutral, ultralong-acting new generation basal insulin analog developed by NovoNordisk currently in Phase III clinical development. IDeg offers a duration of action of more than 42 hours in adults, much longer than current basal insulin formulations.Objective: The aim of this review is to assess the efficacy and safety data of IDeg in the treatment of type 1 and type 2 diabetes mellitus.Methods: Relevant English language articles from 2010 to 2012 were identified through MEDLINE, PubMed, EMBASE, Scopus, BIOSIS, and Google Scholar. Online conference proceedings of the 71st ADA Scientific Sessions and the 47th EASD Annual Meeting were reviewed. Studies were compared in terms of their study designs, primary and secondary efficacy parameters, and tolerability data.Results: There are a total of nine published trials investigating the clinical efficacy and safety of IDeg in over 3000 subjects with type 1 and 2 diabetes. Only three trials were published in full. All were open-label, randomized multicenter trials with durations of 16 to 52 weeks. IDeg and coformulations of IDeg with insulin aspart (IAsp were compared to insulin glargine (IGlar, detemir, and biphasic IAsp 30 (BIAsp 30.Conclusion: Based upon the available evidence, there appear to be no reported differences between IDeg and IGlar, detemir, or BIAsp 30 in the reduction of the primary efficacy end-points of HbA1c and mean fasting plasma glucose (FPG concentrations. Only flexible dosing of IDeg provided a significant reduction in FPG compared to IGlar. IDeg demonstrated a significant reduction in nocturnal hypoglycemia in type 1 diabetes. In type 2 diabetes, IDeg reduced the incidence of hypoglycemia by 18% and 58% compared to IGlar and

Hyperinsulinemia in the physiologic range is not superior to short-term fasting in suppressing insulin secretion in obese men.

Science.gov (United States)

Pincelli, A I; Brunani, A; Caumo, A; Scacchi, M; Pasqualinotto, L; Tibaldi, A; Dubini, A; Bonadonna, S; Cavagnini, F

2001-01-01

The negative-feedback control exerted by plasma insulin on beta-cell insulin release in normal-weight and obese subjects is still a matter of debate. Subjects submitted to a euglycemic insulin clamp undergo a suppression of insulin secretion that is due to both the infused insulin and the 2- to 3-hour fast during the procedure. We elected to elucidate the role of physiologic hyperinsulinemia per se in the insulin negative autofeedback in obese men. Ten men with massive uncomplicated obesity (age, 18 to 37 years; body mass index [BMI], 41 +/- 1.15 kg/m2) and 6 normal-weight healthy men (age, 22 to 30 years; BMI, 22 +/- 0.28 kg/m2) underwent 2 studies in random order: (1) a euglycemic-hyperinsulinemic glucose clamp with an insulin infusion rate of 1 mU/kg/min and (2) a control study with saline infusion. Serum C-peptide concentrations were significantly higher in obese versus control subjects at baseline (2.54 +/- 0.178 v 1.63 +/- 0.256 ng/mL, P < .05). Exogenous insulin infusion significantly suppressed serum C-peptide at steady state ([SS] last 30 minutes of insulin or saline infusion) in controls (mean of the last 4 measurements from 120 minutes to 150 minutes, 0.86 +/- 0.306 ng/mL, P < .05 vbaseline) but not in obese patients (2.03 +/- 0.26 ng/mL, nonsignificant [NS] v baseline). During the saline infusion studies, C-peptide levels slightly and similarly declined over time in both groups (2.71 +/- 0.350 at baseline v 2.31 +/- 0.300 ng/mL at SS in obese patients, NS, and 1.96 +/- 0.189 v 1.62 +/- 0.150 ng/mL in controls, NS). This study shows that in obese men hyperinsulinemia within the postprandial range is not superior to a 2.5-hour fast for the suppression of beta-cell activity, suggesting an impairment of the insulin negative autofeedback in this clinical condition.

The radioimmunological determination of the insulin level in the early postnatal period of the pigs

International Nuclear Information System (INIS)

Nowak, J.; Staszak, B.; Slebodzinski, A.

1980-01-01

The insulin level determined by means of the radioimmunoassay, in piglets, 1 - 21 days of age revealed marked changes with age of the animals, as illustrated by the hormonal profiles. In general, the postnatal insuline profile was characterized by a quick rise in the serum hormone concentration - the postnatal hiperinsulinemia - observed already in some litters within the first 48 hours of life. The peak of the hormone concentration was followed by a decrease to a relatively constant but low level, between the third day and 10 - 14 day. In the absolute terms, the insulin concentration at 0 - 6 hours averaged from 3.3+-1.42 to 11.0+-1.44 μU/ml and then increased to the maximum from 19.8+-1.44 to 30.3+-8.81 μU/ml (means +- S.E., p<0.01) found between 12 - 36 hour of life. In some of the pigs a low or a high insulin level came by turns. Any insulin level above 16 μU/ml was classified as ''an insulin peak'' and that below 8 μU/ml as ''an insulin depression''. The frequency of the peaks and the depressions per day was the highest during the first 2 days of life, that is during the period known from the highest mortality in this species. The preliminary observation suggest that a high frequency of the insulin depressions is somewhat related to the lower vitality or to the hypoglycemia state. (author)

A Retrospective Chart Review of Two Different Insulin Administration Systems on Glycemic Control in Older Adults in Long-Term Care.

Science.gov (United States)

Boonin, Alan; Balinski, Brenda; Sauter, Jerry; Martinez, Joe; Abbott, Scott

2017-01-01

The current retrospective chart review compared glycemic control and cost impact of two insulin administration systems, V-Go ® versus usual care with standard of care (SOC) insulin injections, in eight patients residing in a nursing home (NH). A total of 1,937 blood glucose (BG) values were collected over 61 days. Significant improvements were observed for the V-Go versus SOC group in time in range 100 mg/dL to 200 mg/dL (V-Go 59.09% vs. SOC 34.02%; p < 0.001), reduced BG fluctuations as measured by standard deviation (V-Go 61.2 vs. SOC 92.1; p < 0.001), and improved mean daily BG (V-Go 159.38 mg/dL vs. SOC 223.86 mg/dL; p < 0.001). The estimated A1c change, calculated from BG values, decreased from 8.9% to 7.2% in the V-Go group and increased from 9.0% to 9.4% in the SOC group. Compared to SOC, use of V-Go decreased the mean time for insulin administration by nursing staff by 26.3 minutes per patient per day and associated labor costs by $328.75 per patient per month. Insulin administration with V-Go may improve glycemic control and reduce administration costs compared to existing care in the NH setting. [Journal of Gerontological Nursing, 43(1), 10-16.]. Copyright 2017, SLACK Incorporated.

Effect of insulin catheter wear-time on subcutaneous adipose tissue blood flow and insulin absorption in humans

DEFF Research Database (Denmark)

Clausen, Trine Schnedler; Kaastrup, Peter; Stallknecht, Bente

2009-01-01

blood flow (ATBF) and absorption of the rapid-acting insulin analog insulin aspart over a period of 4 days. METHODS: Teflon insulin catheters (Medtronic, Minneapolis, MN) were inserted into the abdominal SAT of 10 healthy men without diabetes (mean +/- SEM age, 23.0 +/- 1.1 years; body mass index, 22...... +/- 3 min on day 0 to 45 +/- 4 min on day 4 (P = 0.019). Neither peak plasma concentration nor area under the curve of insulin aspart changed significantly. CONCLUSIONS: Insertion of a Teflon insulin catheter into the SAT results in increased ATBF and faster absorption of insulin aspart in a period of 4...

Metformin and insulin receptors

International Nuclear Information System (INIS)

Vigneri, R.; Gullo, D.; Pezzino, V.

1984-01-01

The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

Clinical experience with insulin detemir type 2 diabetes mellitus, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Rabat-Sale-Zemmour-Zaer Region cohort of the A1chieve study.

Science.gov (United States)

Chraibi, Abdelmjid; Belmejdoub, Ghizlane

2013-11-01

The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66 726) in routine clinical care across four continents. Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Rabat-Sale-Zemmour-Zaer region, Morocco. A total of 424 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 177), insulin detemir (n = 150), insulin aspart (n = 11), basal insulin plus insulin aspart (n = 45) and other insulin combinations (n = 41). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 10.1%) and insulin user (mean HbA1c: 9.4%) groups. After 24 weeks of treatment, all the study groups showed improvement in HbA1c (insulin naïve: -2.5%, insulin users: -1.8%). Major hypoglycaemia was observed in the insulin user group after 24 weeks (0.1 events/patient-year). SADRs were reported in 0.5% of insulin users. Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Insulin secretion after short- and long-term low-grade free fatty acid infusion in men with increased risk of developing type 2 diabetes

DEFF Research Database (Denmark)

Storgaard, Heidi; Jensen, Christine B; Vaag, Allan A

2003-01-01

We studied the effect of a low-grade short- and long-term 20% Intralipid infusion (0.4 mL(-1) x kg(-1) x h(-1)) on insulin secretion and insulin action in 15 elderly obese men; 7 glucose intolerant first-degree relatives of type 2 diabetic patients (impaired glucose tolerance [IGT] relatives) and 8...... healthy controls of similar age and body mass index (BMI). Intravenous glucose tolerance test (IVGTT) and a graded glucose infusion (dose-response test [DORE]) were performed to determine first phase insulin response and to explore the dose response relationship between glucose concentration and insulin...... secretion rates (ISR). ISR were calculated by deconvolution of plasma C-peptide concentrations. Insulin action was determined by performing a 120-minute hyperinsulinemic euglycemic clamp. All tests were performed 3 times, preceded by 0, 2, or 24 hours Intralipid infusion. Disposition indices (DI) were...

Short-Term Exercise Training Improves Insulin Sensitivity but Does Not Inhibit Inflammatory Pathways in Immune Cells from Insulin-Resistant Subjects

Directory of Open Access Journals (Sweden)

Sara M. Reyna

2013-01-01

Full Text Available Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD. Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells. Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise. Peripheral mononuclear cells (PMNC were obtained for determination of Toll-like receptor (TLR 2 and 4 protein content and mitogen-activated protein kinase phosphorylation. Results. Compared with that in lean individuals, TLR4 protein content was increased by 4.2-fold in diabetic subjects. This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK phosphorylation. Exercise improved insulin sensitivity in the lean, obese, and type 2 diabetes groups. However, exercise did not affect TLR content or ERK phosphorylation. Conclusions. TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals.

Short-term exercise training improves insulin sensitivity but does not inhibit inflammatory pathways in immune cells from insulin-resistant subjects.

Science.gov (United States)

Reyna, Sara M; Tantiwong, Puntip; Cersosimo, Eugenio; Defronzo, Ralph A; Sriwijitkamol, Apiradee; Musi, Nicolas

2013-01-01

Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD). Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells. Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise. Peripheral mononuclear cells (PMNC) were obtained for determination of Toll-like receptor (TLR) 2 and 4 protein content and mitogen-activated protein kinase phosphorylation. Results. Compared with that in lean individuals, TLR4 protein content was increased by 4.2-fold in diabetic subjects. This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK) phosphorylation. Exercise improved insulin sensitivity in the lean, obese, and type 2 diabetes groups. However, exercise did not affect TLR content or ERK phosphorylation. Conclusions. TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals.

Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

Science.gov (United States)

Kang, S; Brange, J; Burch, A; Vølund, A; Owens, D R

1991-11-01

To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and

Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes.

Science.gov (United States)

Farrar, Diane; Tuffnell, Derek J; West, Jane; West, Helen M

2016-06-07

).There was no clear evidence of differences in the maternal secondary outcomes: maternal weight gain during pregnancy, 24 hour mean blood glucose in each trimester, mean maternal HbA1c in each trimester, maternal hypoglycaemia, and maternal hyperglycaemia. The included studies did not report several GRADE outcomes: perineal trauma, return to pre-pregnancy weight, postnatal depression, induction of labour. Many maternal secondary outcomes were also not reported.In two trials, including a total of 61 infants, CSII was associated with an increase in mean birthweight compared with MDI (mean difference (MD) 220.56 g, 95% CI -2.09 g to 443.20 g; P = 0.05). However, the large CI including anything from a small reduction to an increase in mean birthweight and the lack of a difference in macrosomia rate (RR 3.20, CI 0.14 to 72.62; two trials, 61 infants) suggests uncertainty. Large-for-gestational age (see above), andsmall-for-gestational age also suggests uncertainty of effect. No significant differences were found in: gestation at delivery, preterm birth pregnant women with diabetes and their infants, and the results of further studies may differ substantially from those presented in this review. There is no evidence to support the use of one particular form of insulin administration over another for pregnant women with diabetes. There are only a small number of trials appropriate for meta-analysis, a small number of women included and questionable generalisability of the trial population.Pump technology has progressed since these trials were undertaken. Well-designed randomised trials are required to evaluate comparisons such as patch pumps against MDI and more conventional CSII against MDI. These trials should be adequately powered to assess the effect of interventions, and report the core set of outcomes used in Cochrane reviews of diabetes in pregnancy. Trials to assess the effects of pumps on birthweight and macrosomia rates are needed. It would be beneficial for future trials

Expression of glycogen synthase and phosphofructokinase in muscle from type 1 (insulin-dependent) diabetic patients before and after intensive insulin treatment

DEFF Research Database (Denmark)

Vestergaard, H; Andersen, P H; Lund, S

1994-01-01

The aim of the present study was to determine whether short-term appropriate insulinization of Type 1 (insulin-dependent) diabetic patients in long-term poor glycaemic control (HbA1C > 9.5%) was associated with an adaptive regulation of the activity and gene expression of key proteins in muscle...... glycogen storage and glycolysis: glycogen synthase and phosphofructokinase, respectively. In nine diabetic patients biopsies of quadriceps muscle were taken before and 24-h after intensified insulin therapy and compared to findings in eight control subjects. Subcutaneous injections of rapid acting insulin...... were given at 3-h intervals to improve glycaemic control in diabetic patients (fasting plasma glucose decreased from 20.8 +/- 0.8 to 8.7 +/- 0.8 mmol/l whereas fasting serum insulin increased from 59 +/- 8 to 173 +/- 3 pmol/l). Before intensified insulin therapy, analysis of muscle biopsies from...

7 CFR 868.1 - Meaning of terms.

Science.gov (United States)

2010-01-01

... following terms have the meanings given for them in this paragraph. (1) Act. The Agricultural Marketing Act... established scientific principles and laboratory procedures. [53 FR 3722, Feb. 9, 1988, as amended at 60 FR...

Pharmacokinetics of a porcine insulin zinc suspension in diabetic dogs.

Science.gov (United States)

Graham, P A; Nash, A S; McKellar, Q A

1997-10-01

Ten dogs with naturally occurring diabetes mellitus were injected with a highly purified porcine insulin zinc suspension at a dose according to their expected requirement. Plasma insulin and glucose concentrations were measured at two-hourly intervals over 24 hours following injection. There were either one or two peaks in plasma insulin concentration: one at about four hours (mean 4.3 +/- 1.3 [SD]) and another at about 11 hours (mean 11 +/- 1.85) after the injection. The second insulin peak was seen in only eight dogs. Persistence of elevated plasma insulin concentrations ranged from 14 to 24 hours (mean 17.4 +/- 3.65). These results compare favourably with those published for other intermediate-acting insulin preparations used to treat canine diabetes mellitus and suggest that this preparation has useful properties for the successful management of many canine diabetics.

Clinical experience with insulin detemir type 2 diabetes mellitus, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Rabat-Sale-Zemmour-Zaer Region cohort of the A 1 chieve study

Directory of Open Access Journals (Sweden)

Abdelmjid Chraibi

2013-01-01

Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66 726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Rabat-Sale-Zemmour-Zaer region, Morocco. Results: A total of 424 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 177, insulin detemir (n = 150, insulin aspart (n = 11, basal insulin plus insulin aspart (n = 45 and other insulin combinations (n = 41. At baseline glycaemic control was poor for both insulin naïve (mean HbA 1 c: 10.1% and insulin user (mean HbA 1 c: 9.4% groups. After 24 weeks of treatment, all the study groups showed improvement in HbA 1 c (insulin naïve: −2.5%, insulin users: −1.8%. Major hypoglycaemia was observed in the insulin user group after 24 weeks (0.1 events/patient-year. SADRs were reported in 0.5% of insulin users. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Icodextrine and insulin resistance in continuous ambulatory peritoneal dialysis patients.

Science.gov (United States)

Canbakan, Mustafa; Sahin, Gülizar Manga

2007-01-01

Insulin resistance is commonly observed in uremic patients. Glucose-based peritoneal dialysis solutions have long-term metabolic complications like hyperinsulinemia, hyperlipidemia, and obesity. The purpose of this study was to examine the insulin resistance in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with standard glucose and icodextrin containing solutions. The entire non diabetic CAPD patients of our center were studied: forty-four patients in all who were on CAPD treatment for 36.2 +/- 23.7 months. Twenty-seven of them (11 male and 16 female) with a mean age of 46 +/- 16 years were treated with standard glucose solutions (glucose group). The other 17 patients (10 male and 7 female) with a mean age of 49 +/- 16 years were treated with standard glucose solutions during the day and icodextrin dwell during the night, for a median of 12 +/- 6.3 months (icodextrin group). Morning fasting serum insulin levels were 20.59 +/- 17.86 in the glucose group and 10.15 +/- 6.87 in the icodextrin group (p = 0.0001). Homeostasis Model Assessment Method scores of the glucose group were significantly higher (4.8+/-4.1 vs 2.3+/- 1.7; p = 0.025) than the icodextrin group. A significant positive correlation of HOMA score with insulin, fasting plasma glucose, and triglyceride levels were found in HOMA (IR+) patients. Twenty patients of the icodextrin group (74%) and 15 patients of the glucose group (88%) were hypertensive, but there was no statistically significant difference between the two groups (p = 0.13). The groups showed no significant differences for body mass index and serum levels of glucose, total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, triglyceride, intact parathyroid hormone (iPTH), and fibrinogen. In conclusion, the use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.

Insulin Resistance of Puberty.

Science.gov (United States)

Kelsey, Megan M; Zeitler, Philip S

2016-07-01

Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity.

Comparison of Subcutaneous Regular Insulin and Lispro Insulin in Diabetics Receiving Continuous Nutrition

Science.gov (United States)

Stull, Mamie C.; Strilka, Richard J.; Clemens, Michael S.; Armen, Scott B.

2015-01-01

Background: Optimal management of non–critically ill patients with diabetes maintained on continuous enteral feeding (CEN) is poorly defined. Subcutaneous (SQ) lispro and SQ regular insulin were compared in a simulated type 1 and type 2 diabetic patient receiving CEN. Method: A glucose-insulin feedback mathematical model was employed to simulate type 1 and type 2 diabetic patients on CEN. Each patient received 25 SQ injections of regular insulin or insulin lispro, ranging from 0-6 U. Primary endpoints were the change in mean glucose concentration (MGC) and change in glucose variability (GV); hypoglycemic episodes were also reported. The model was first validated against patient data. Results: Both SQ insulin preparations linearly decreased MGC, however, SQ regular insulin decreased GV whereas SQ lispro tended to increase GV. Hourly glucose concentration measurements were needed to capture the increase in GV. In the type 2 diabetic patient, “rebound hyperglycemia” occurred after SQ lispro was rapidly metabolized. Although neither SQ insulin preparation caused hypoglycemia, SQ lispro significantly lowered MGC compared to SQ regular insulin. Thus, it may be more likely to cause hypoglycemia. Analyses of the detailed glucose concentration versus time data suggest that the inferior performance of lispro resulted from its shorter duration of action. Finally, the effects of both insulin preparations persisted beyond their duration of actions in the type 2 diabetic patient. Conclusions: Subcutaneous regular insulin may be the short-acting insulin preparation of choice for this subset of diabetic patients. Clinical trial is required before a definitive recommendation can be made. PMID:26134836

Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation.

Science.gov (United States)

Frank, N; Hermida, P; Sanchez-Londoño, A; Singh, R; Gradil, C M; Uricchio, C K

2017-07-01

Octreotide is a somatostatin analog that suppresses insulin secretion. We hypothesized that octreotide would suppress insulin concentrations in horses and that normal (N) horses and those with insulin dysregulation (ID) would differ significantly in their plasma glucose and insulin responses to administration of octreotide. Twelve horses, N = 5, ID = 7. Prospective study. An oral sugar test was performed to assign horses to N and ID groups. Octreotide (1.0 μg/kg IV) was then administered, and blood was collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, 75, and 90 minute, and 2, 3, 4, 6, 8, 12, and 24 hour for measurement of glucose and insulin concentrations. Area under the curve (AUC) values were calculated. Mean AUC values for glucose and insulin did not differ between normal (n = 5) and ID (n = 7) groups after octreotide injection. Significant time (P glucose and insulin concentrations. A group × time interaction (P = .091) was detected for insulin concentrations after administration of octreotide, but the group (P = .33) effect was not significant. Octreotide suppresses insulin secretion, resulting in hyperglycemia, and then concentrations increase above baseline as glycemic control is restored. Our hypothesis that octreotide causes insulin concentrations to decrease in horses was supported, but differences between N and ID groups did not reach statistical significance when blood glucose and insulin responses were compared. The utility of an octreotide response test remains to be determined. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Intramyocellular lipid content and insulin sensitivity are increased following a short-term low-glycemic index diet and exercise intervention

DEFF Research Database (Denmark)

Haus, Jacob M; Solomon, Thomas; Lu, Lan

2011-01-01

The relationship between intramyocellular (IMCL) and extramyocellular lipid (EMCL) accumulation and skeletal muscle insulin resistance is complex and dynamic. We examined the effect of a short-term (7-day) low-glycemic index (LGI) diet and aerobic exercise training intervention (EX) on IMCL and i...

Classifying insulin regimens--difficulties and proposal for comprehensive new definitions.

Science.gov (United States)

Neu, A; Lange, K; Barrett, T; Cameron, F; Dorchy, H; Hoey, H; Jarosz-Chobot, P; Mortensen, H B; Robert, J-J; Robertson, K; de Beaufort, C

2015-09-01

Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1 diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin regimens reflecting current diabetes management in childhood and adolescence. The HSG--founded in 1994--is an international group representing 24 highly experienced pediatric diabetes centers, from Europe, Japan, North America and Australia. Different benchmarking studies of the HSG revealed a broad variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides the concepts 'conventional' and 'intensified', several other terms for the characterization of insulin regimens are in use: Basal Bolus Concept (BBC), multiple daily injections (MDI), and flexible insulin therapy (FIT) are most frequently used, although none of these expressions is clearly or consistently defined. The proposed new classification for insulin management will be comprehensive, simple, and catchy. Currently available terms were included. This classification may offer the opportunity to compare therapeutic strategies without the currently existing confusion on the insulin regimen. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats

Energy Technology Data Exchange (ETDEWEB)

Vikram, Ajit [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab 160 062 (India); Jena, Gopabandhu, E-mail: gbjena@gmail.com [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab 160 062 (India)

2010-07-23

Research highlights: {yields}Insulin receptor antagonist S961 causes hyperglycemia, hyperinsulinemia and insulin resistance in rats. {yields}Peroxysome-proliferator-activated-receptor-gamma agonist pioglitazone improves S961 induced hyperglycemia and glucose intolerance. {yields}Long term treatment with insulin receptor antagonist S961 results in the decreased adiposity and hepatic glycogen content. {yields}Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. -- Abstract: Impairment in the insulin receptor signaling and insulin mediated effects are the key features of type 2 diabetes. Here we report that S961, a peptide insulin receptor antagonist induces hyperglycemia, hyperinsulinemia ({approx}18-fold), glucose intolerance and impairment in the insulin mediated glucose disposal in the Sprague-Dawley rats. Further, long-term S961 treatment (15 day, 10 nM/kg/day) depletes energy storage as evident from decrease in the adiposity and hepatic glycogen content. However, peroxysome-proliferator-activated-receptor-gamma (PPAR{gamma}) agonist pioglitazone significantly (P < 0.001) restored S961 induced hyperglycemia (196.73 {+-} 16.32 vs. 126.37 {+-} 27.07 mg/dl) and glucose intolerance ({approx}78%). Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. Further, results of the present study reconfirms and provide direct evidence to the crucial role of insulin receptor signaling in the glucose homeostasis and fuel metabolism.

Insulin Initiation in Insulin-Naïve Korean Type 2 Diabetic Patients Inadequately Controlled on Oral Antidiabetic Drugs in Real-World Practice: The Modality of Insulin Treatment Evaluation Study

Directory of Open Access Journals (Sweden)

Sang Soo Kim

2015-12-01

Full Text Available BackgroundThe Modality of Insulin Treatment Evaluation (MOTIV study was performed to provide real-world data concerning insulin initiation in Korean type 2 diabetes mellitus (T2DM patients with inadequate glycemic control with oral hypoglycemic agents (OHAs.MethodsThis multicenter, non-interventional, prospective, observational study enrolled T2DM patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0% who had been on OHAs for ≥3 months and were already decided to introduce basal insulin by their physician prior to the start of the study. All treatment decisions were at the physician's discretion to reflect real-world practice.ResultsA total of 9,196 patients were enrolled, and 8,636 patients were included in the analysis (mean duration of diabetes, 8.9 years; mean HbA1c, 9.2%. Basal insulin plus one OHA was the most frequently (51.0% used regimen. After 6 months of basal insulin treatment, HbA1c decreased to 7.4% and 44.5% of patients reached HbA1c <7%. Body weight increased from 65.2 kg to 65.5 kg, which was not significant. Meanwhile, there was significant increase in the mean daily insulin dose from 16.9 IU at baseline to 24.5 IU at month 6 (P<0.001. Overall, 17.6% of patients experienced at least one hypoglycemic event.ConclusionIn a real-world setting, the initiation of basal insulin is an effective and well-tolerated treatment option in Korean patients with T2DM who are failing to meet targets with OHA therapy.

Insulin resistance in human subjects having impaired glucose regulation

International Nuclear Information System (INIS)

Khan, S.H.; Khan, F.A.; Ijaz, A.

2007-01-01

To determine insulin resistance in human subjects having impaired glucose regulation (IGR) by Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). A total of 100 subjects with impaired glucose regulation were selected for evaluation of metabolic syndrome as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III), along with 47 healthy age and gender-matched controls. Physical examination to determine blood pressure and waist circumference was carried out and so was sampling for plasma glucose, serum triglycerides, HDL-cholesterol and insulin. Insulin resistance was calculated by the HOMA-IR. Finally, subjects with and without metabolic syndrome were compared with controls (n=47), using one-way ANOVA for studying insulin resistance between groups, with Tukey's post-hoc comparison. The frequency of finding metabolic syndrome in cases of IGR remained 47%. The insulin resistance demonstrated stepwise worsening from control population (mean=1.54, 95 % CI: 1.77 - 2.37) to subjects suffering from only IGR (mean=2.07, 95 % CI: 1.77- 2.37) to metabolic syndrome (mean=2.67, 95 %, CI: 2.34 - 3.00) (p < 0.001). Patients with impaired glucose regulation may have significant insulin resistance. It is, thus, recommended that a vigorous search be made to measure insulin resistance in all cases diagnosed to have impaired glucose regulation. (author)

27 CFR 21.11 - Meaning of terms.

Science.gov (United States)

2010-04-01

... taste, aroma, and characteristics generally attributed to rum. S.D.A. Specially denatured alcohol... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Meaning of terms. 21.11 Section 21.11 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT...

Short-term intensive insulin therapy could be the preferred option for new onset Type 2 diabetes mellitus patients with HbA1c > 9.

Science.gov (United States)

Weng, Jianping

2017-10-01

Type 2 diabetes mellitus (T2DM) is a heterogeneous disease. Currently, the typical clinical therapeutic pathway for the disease consists of the stepwise addition of antihyperglycemic preparations over time, followed lastly by insulin therapy when functional β-cell capacity is severely deteriorated. Recognizing the complexity of disease management, personalized (precision) medicine approaches may enable the physician to tailor diabetes treatment based on HbA1c levels, body mass index (BMI), efficacy, risk of hypoglycemia, risk of weight gain, age, safety, cost, and even genetic characteristics. Although insulin therapy has traditionally been recommended as the last option in the sequential treatment algorithm of T2DM, it is notable that several guidelines and consensus statements suggest consideration of insulin as part of a first-line regimen. In the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive T2DM 2017 management algorithm, insulin is recommended for T2DM patients presenting with symptoms and an HbA1c >9.0%. In addition, the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus statement recommends initial insulin therapy as an option when HbA1c ≥9%, and definite consideration with HbA1c ≥10-12%, and mentions that it may be possible to taper off insulin once initial glucotoxicity is reversed and to consider transfer to other types of non-insulin therapies. Based on accumulating evidence, an expert group has endorsed the concept of short-term intensive insulin (STII) therapy as an option for some patients with T2DM at the time of diagnosis. Notably, the latest Israeli guidelines suggest considering immediate, sometimes short-term, insulin treatment for patients with HbA1c >9% or with symptoms. It has been reported that nearly one-quarter (23%) of newly diagnosed T2DM patients in the US had an HbA1c ≥9.0% prior to initiation of treatment. For such

Do we really know what the term talent and talent management means?

DEFF Research Database (Denmark)

Adamsen, Billy

2015-01-01

to something beyond real life, something indefinite and indefinable. In other words, today we do not know specifically what the term “talent” in talent management really means or refers to. Indeed, this is problematical, because in late modernity the term “talent” has become a popular and frequently used key...... term among business consultants and, within the science of human resource management, a cornerstone in the discipline of “talent management”, and not knowing what the term really means will turn any talent discussion, talent identification and talent recruitment into a question of subjectivity......Over the centuries the term “talent” has changed semantically and slowly transformed itself into a floating signifier or become an accidental designator. The term “talent” no longer has one single meaning and a “referent” in real life, but instead a multiplicity of meaning and references...

Insulin Pump Malfunction During Hospitalization: Two Case Reports.

Science.gov (United States)

Faulds, Eileen R; Wyne, Kathleen L; Buschur, Elizabeth O; McDaniel, Jodi; Dungan, Kathleen

2016-06-01

Insulin pump malfunctions and failures continue to occur; however, more severe malfunctions such as the "runaway pump" phenomenon are rarely reported. This article describes two cases of pump malfunction in which pump users appear to have received an unsolicited bolus of insulin resulting in severe episodes of hypoglycemia during hospitalization. Both cases of insulin pump malfunction occurred in the inpatient setting at a large academic medical center in the United States. An analysis of the corresponding insulin pump downloads was performed. The Food and Drug Administration's (FDA's) Manufacturer and User Facility Device Experience (MAUDE) database was searched for similar cases involving Medtronic (Northridge, CA) insulin pumps using the terms "pump," "infusion," "insulin AND malfunction AND Medtronic." The two cases described show remarkable similarities, each demonstrating a severe hypoglycemic event preceded by an infusion site change followed by an alarm. In both cases a rapid spraying of insulin was reported. The insulin pump downloads validated much of the patients' and medical staff's descriptions of events. The FDA's MAUDE database search revealed 425 cases meeting our search term criteria. All cases were reviewed. Seven cases were identified involving independent movement of the reservoir piston. The cases detailed are the first to describe an insulin pump malfunction of this nature in the hospital setting involving unsolicited insulin boluses leading to severe hypoglycemia. The cases are particularly compelling in that they were witnessed by medical personnel. Providers and patients should receive instruction education on the recognition and management of insulin pump malfunction.

Effect of HCV on fasting glucose, fasting insulin and peripheral insulin resistance in first 5 years of infection.

Science.gov (United States)

Ahmed, Naeema; Rashid, Amir; Naveed, Abdul Khaliq; Bashir, Qudsia

2016-02-01

To assess the effects of hepatitis C virus infection in the first 5 years on fasting glucose, fasting insulin and peripheral insulin resistance. The case-control study was conducted at the Army Medical College, Rawalpindi, from December 2011 to November 2012, and comprised subjects recruited from a government hospital in Rawalpindi. The subjects included known cases of hepatitis C virus infection for at least 5 years, and normal healthy controls. Fasting blood samples of all the subjects were collected and analysed for serum fasting insulin and serum fasting glucose levels. Homeostatic model assessment-Insulin resistance was calculated SPSS 11 was used for statistical analysis. Of the 30 subjects, 20(66.6%) were cases, while 10(33.3%) were controls. Serum fasting glucose mean level in cases was 89.55±9.53 compared to 84.40±9.80 in the controls (p=0.188). The mean serum fasting insulin in controls was 7.52±3.23 and 6.79±3.30 in cases (p=0.567). Homeostatic model assessment-Insulin resistance level in controls was 1.60±0.76 and In the cases it was 1.49±0.74 (p=0.695). Peripheral insulin resistance and development of type 2 diabetes as a complication of hepatitis C virus infection was not likely at least within the first five years of infection.

Mean value estimates of the error terms of Lehmer problem

Indian Academy of Sciences (India)

Mean value estimates of the error terms of Lehmer problem. DONGMEI REN1 and YAMING ... For further properties of N(a,p) in [6], he studied the mean square value of the error term. E(a, p) = N(a,p) − 1. 2 (p − 1) ..... [1] Apostol Tom M, Introduction to Analytic Number Theory (New York: Springer-Verlag). (1976). [2] Guy R K ...

Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes

DEFF Research Database (Denmark)

Lund, Søren S; Tarnow, Lise; Frandsen, Merete

2009-01-01

. Patients had had type 2 diabetes for approximately 10 years. At the end of treatment, HbA(1c) concentration was reduced by a similar amount in the two treatment groups (insulin plus metformin: mean (standard deviation) HbA(1c) 8.15% (1.32) v 6.72% (0.66); insulin plus repaglinide: 8.07% (1.49) v 6.90% (0......OBJECTIVES: To study the effect of insulin treatment in combination with metformin or an insulin secretagogue, repaglinide, on glycaemic regulation in non-obese patients with type 2 diabetes. DESIGN: Randomised, double blind, double dummy, parallel trial. SETTING: Secondary care in Denmark between......% confidence interval -4.07 to -0.95). CONCLUSIONS: In non-obese patients with type 2 diabetes and poor glycaemic regulation on oral hypoglycaemic agents, overall glycaemic regulation with insulin in combination with metformin was equivalent to that with insulin plus repaglinide. Weight gain seemed less...

Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice.

Science.gov (United States)

Jung, Dae Young; Ko, Hwi Jin; Lichtman, Eben I; Lee, Eunjung; Lawton, Elizabeth; Ong, Helena; Yu, Kristine; Azuma, Yoshihiro; Friedline, Randall H; Lee, Ki Won; Kim, Jason K

2013-05-01

Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.

27 CFR 70.601 - Meaning of terms.

Science.gov (United States)

2010-04-01

... otherwise within the scope of the term defined. Alcoholic liquors or liquors. Distilled spirits, wines, and... claim under this subpart. Commissioner of Customs. The Commissioner of Customs, U.S. Customs Service... paid or determined on spirits. (2) With respect to wines, “tax” means the internal revenue tax that is...

Chitosan nanofibers for transbuccal insulin delivery.

Science.gov (United States)

Lancina, Michael G; Shankar, Roopa Kanakatti; Yang, Hu

2017-05-01

In this work, they aimed at producing chitosan based nanofiber mats capable of delivering insulin via the buccal mucosa. Chitosan was electrospun into nanofibers using poly(ethylene oxide) (PEO) as a carrier molecule in various feed ratios. The mechanical properties and degradation kinetics of the fibers were measured. Insulin release rates were determined in vitro using an ELISA assay. The bioactivity of released insulin was measured in terms of Akt activation in pre-adipocytes. Insulin permeation across the buccal mucosa was measured in an ex-vivo porcine transbuccal model. Fiber morphology, mechanical properties, and in vitro stability were dependent on PEO feed ratio. Lower PEO content blends produced smaller diameter fibers with significantly faster insulin release kinetics. Insulin showed no reduction in bioactivity due to electrospinning. Buccal permeation of insulin facilitated by high chitosan content blends was significantly higher than that of free insulin. Taken together, the work demonstrates that chitosan-based nanofibers have the potential to serve as a transbuccal insulin delivery vehicle. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1252-1259, 2017. © 2017 Wiley Periodicals, Inc.

Effect of fructose consumption on insulin sensitivity in nondiabetic subjects: a systematic review and meta-analysis of diet-intervention trials.

Science.gov (United States)

Ter Horst, Kasper W; Schene, Merle R; Holman, Rebecca; Romijn, Johannes A; Serlie, Mireille J

2016-12-01

High fructose consumption has been suggested to contribute to several features of metabolic syndrome including insulin resistance, but to our knowledge, no previous meta-analyses have investigated the effect of fructose on insulin sensitivity in nondiabetic subjects. We performed a systematic review and meta-analysis of controlled diet-intervention studies in nondiabetic subjects to determine the effect of fructose on insulin sensitivity. We searched MEDLINE, EMBASE, and the Cochrane Library for relevant trials on the basis of predetermined eligibility criteria. Two investigators independently performed the study selection, quality assessment, and data extraction. Results were pooled with the use of the generic inverse-variance method with random effects weighting and were expressed as mean differences (MDs) or standardized mean differences (SMDs) with 95% CIs. Twenty-nine articles that described 46 comparisons in 1005 normal-weight and overweight or obese participants met the eligibility criteria. An energy-matched (isocaloric) exchange of dietary carbohydrates by fructose promoted hepatic insulin resistance (SMD: 0.47; 95% CI: 0.03, 0.91; P = 0.04) but had no effect on fasting plasma insulin concentrations (MD: -0.79 pmol/L; 95% CI: -6.41, 4.84 pmol/L; P = 0.78), the homeostasis model assessment of insulin resistance (HOMA-IR) (MD: 0.13; 95% CI: -0.07, 0.34; P = 0.21), or glucose disposal rates under euglycemic hyperinsulinemic clamp conditions (SMD: 0.00; 95% CI: 20.41, 0.41; P = 1.00). Hypercaloric fructose (∼25% excess of energy compared with that of the weight-maintenance control diet) raised fasting plasma insulin concentrations (MD: 3.38 pmol/L; 95% CI: 0.03, 6.73 pmol/L; P fructose consumption, in isocaloric exchange or in hypercaloric supplementation, promotes the development of hepatic insulin resistance in nondiabetic adults without affecting peripheral or muscle insulin sensitivity. Larger and longer-term studies are needed to assess whether real

S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats

International Nuclear Information System (INIS)

Vikram, Ajit; Jena, Gopabandhu

2010-01-01

Research highlights: →Insulin receptor antagonist S961 causes hyperglycemia, hyperinsulinemia and insulin resistance in rats. →Peroxysome-proliferator-activated-receptor-gamma agonist pioglitazone improves S961 induced hyperglycemia and glucose intolerance. →Long term treatment with insulin receptor antagonist S961 results in the decreased adiposity and hepatic glycogen content. →Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. -- Abstract: Impairment in the insulin receptor signaling and insulin mediated effects are the key features of type 2 diabetes. Here we report that S961, a peptide insulin receptor antagonist induces hyperglycemia, hyperinsulinemia (∼18-fold), glucose intolerance and impairment in the insulin mediated glucose disposal in the Sprague-Dawley rats. Further, long-term S961 treatment (15 day, 10 nM/kg/day) depletes energy storage as evident from decrease in the adiposity and hepatic glycogen content. However, peroxysome-proliferator-activated-receptor-gamma (PPARγ) agonist pioglitazone significantly (P < 0.001) restored S961 induced hyperglycemia (196.73 ± 16.32 vs. 126.37 ± 27.07 mg/dl) and glucose intolerance (∼78%). Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. Further, results of the present study reconfirms and provide direct evidence to the crucial role of insulin receptor signaling in the glucose homeostasis and fuel metabolism.

Novel Simple Insulin Delivery Device Reduces Barriers to Insulin Therapy in Type 2 Diabetes

Science.gov (United States)

Hermanns, Norbert; Lilly, Leslie C.; Mader, Julia K.; Aberer, Felix; Ribitsch, Anja; Kojzar, Harald; Warner, Jay; Pieber, Thomas R.

2015-01-01

Background: The PaQ® insulin delivery system is a simple-to-use patch-on device that provides preset basal rates and bolus insulin on demand. In addition to feasibility of use, safety, and efficacy (reported elsewhere), this study analyzed the impact of PaQ on patient-reported outcomes, including barriers to insulin treatment, diabetes-related distress, and attitudes toward insulin therapy in patients with type 2 diabetes on a stable multiple daily injection (MDI) regimen. Methods: This single-center, open-label, single-arm study comprised three 2-week periods: baseline (MDI), transition from MDI to PaQ, and PaQ treatment. Validated questionnaires were administered during the baseline and PaQ treatment periods: Barriers to Insulin Treatment questionnaire (BIT), Insulin Treatment Appraisal Scale (ITAS), and Problem Areas in Diabetes scale (PAID). Results: Eighteen patients (age 59 ± 5 years, diabetes duration 15 ± 7 years, 21% female, HbA1c 7.7 ± 0.7%) completed the questionnaires. There was a strong, significant effect of PaQ use in mean BIT total scores (difference [D] = −5.4 ± 0.7.7, P = .01, effect size [d] = 0.70). Patients perceived less stigmatization by insulin injection (D = −2.2 ± 6.2, P = .18, d = 0.35), increased positive outcome (D = 1.9 ± 6.6, P = .17, d = 0.29), and less fear of injections (1.3 ± 4.8, P = .55, d = 0.28). Mean change in ITAS scores after PaQ device use showed a nonsignificant improvement of 1.71 ± 5.63 but moderate effect size (d = 0.30, P = .14). No increase in PAID scores was seen. Conclusions: The results and moderate to large effects sizes suggest that PaQ device use has beneficial and clinically relevant effects to overcoming barriers to and negative appraisal of insulin treatment, without increasing other diabetes-related distress. PMID:25670847

Effects of short-term metformin treatment on insulin sensitivity of blood glucose and free fatty acids.

Science.gov (United States)

Iannello, S; Camuto, M; Cavaleri, A; Milazzo, P; Pisano, M G; Bellomia, D; Belfiore, F

2004-01-01

Based on the known effect of metformin (MET) in improving insulin sensitivity in type 2 diabetes, with the scope to focus the effects on glycaemic and free fatty acids (FFA) levels, we studied the effects of a short-term treatment with this drug in obese subjects and obese patients with diabetes or family history of diabetes (FHD). We used a method to allow us to evaluate the possible difference of insulin sensibility with regard to the insulin action on glycaemia and blood FFA, both in the basal state and during oral glucose tolerance test (OGTT). Insulin sensitivity was investigated before and after MET treatment (850 mg bid for 10 days) in seven obese subjects with normal glucose tolerance and without FHD and 13 obese patients with diabetes (n=7) or FHD (n=6). By using specifically designed formulae, we calculated four insulin-sensitivity indices (ISI) from basal level (b) and area values (a) (during OGTT) of insulinaemia, glycaemia (gly) or FFA (ffa), namely: ISI (gly)-b, ISI (gly)-a, ISI (ffa)-b and ISI (ffa)-a. In patients with diabetes or FHD, MET improved ISI (gly)-b (0.79 +/- 0.06 vs. 0.59 +/- 0.07, p<0.001) and ISI (gly)-a (0.69 +/- 0.09 vs. 0.51 +/- 0.07, p<0.05), whereas only minor changes occurred for ISI (ffa)-b and ISI (ffa)-a. In contrast, in simple obese subjects, MET induced further deterioration of both ISI (gly)-a (0.47 +/- 0.07 vs. 0.64 +/- 0.10, p<0.01) and ISI (ffa)-a (0.43 +/- 0.07 vs. 0.55 +/- 0.08, p<0.05). Fasting level and total area of lactate were high in the obese patients and were not affected by MET. A statistically significant increase (p<0.01), however, was observed for the 'decremental' area of lactate in obese subjects with diabetes or FHD, which might probably contribute to the reduction of insulin resistance induced by the drug in these patients. Although the low number of subjects studied precludes absolute conclusions, data would suggest that MET improved ISI towards glucose but not towards FFA, in the diabetic and

Short-term memory and strategy use in children with insulin-dependent diabetes mellitus.

Science.gov (United States)

Wolters, C A; Yu, S L; Hagen, J W; Kail, R

1996-12-01

The present study was designed to examine recall and rehearsal in short-term memory among children with insulin-dependent diabetes mellitus (IDDM). Children with onset of IDDM before age 5 years, children with onset after 5 years, and children without IDDM were administered a measure of short-term memory that provides information about rehearsal as well as level of recall. Children with later onset of diabetes and children without IDDM were expected to recall more words and use more effective rehearsal strategies than children with early onset of diabetes. Results indicate that children diagnosed with IDDM early in life used similar rehearsal strategies but recalled fewer words than children with later onset of diabetes and children without IDDM. In addition, results provide evidence that children who are in poor control of their diabetes did not use strategies designed to increase recall as often, or as well as, children in better control of their diabetes.

Long-term efficacy and safety of vildagliptin add-on therapy in type 2 diabetes mellitus with insulin treatment.

Science.gov (United States)

Kanazawa, Ippei; Tanaka, Ken-Ichiro; Notsu, Masakazu; Tanaka, Sayuri; Kiyohara, Nobuaki; Koike, Sayo; Yamane, Yuko; Tada, Yuko; Sasaki, Motofumi; Yamauchi, Mika; Sugimoto, Toshitsugu

2017-01-01

The use of dipeptidyl peptidase (DPP)-4 inhibitors in patients with type 2 diabetes treated with insulin may be beneficial. However, the long-term efficacy and safety of vildagliptin add-on therapy in these patients remains unclear. A total of 73 patients with type 2 diabetes treated with insulin were randomly assigned to receive either add-on therapy of vildagliptin (n=37) or conventional therapy without DPP-4 inhibitors (n=36) for glucose control. Hemoglobin A1c (HbA1c) levels, dose and number of insulin injections, number of hypoglycemia episodes, and liver and renal function were monitored for 2years. The baseline characteristics of subjects, including age, dose of insulin injections, or HbA1c levels, did not differ between the two groups. In the vildagliptin group, HbA1c levels significantly decreased and the significance of HbA1c reduction was maintained for 24months (from 8.0±1.2% to 7.4±1.0%, pinsulin injections significantly reduced (-5.6units, p1, and -0.9 times, p1). However, these parameters were unchanged in the control group. The number of patients who experienced three or more episodes of hypoglycemia per year was significantly lower in the vildagliptin group (n=4) than in the control group (n=11) (odds ratio, 0.28; 95% confidence interval, 0.08-0.97; pinsulin treatment for 24months was well tolerated and led to sustained reductions in HbA1c, the dose and number of insulin injections, and the risk of hypoglycemia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

27 CFR 19.907 - Meaning of terms.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Meaning of terms. 19.907 Section 19.907 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... gas, or coal. This chapter. Title 27, Code of Federal Regulations, Chapter I [27 CFR Chapter I...

Patient safety and minimizing risk with insulin administration - role of insulin degludec.

Science.gov (United States)

Aye, Myint M; Atkin, Stephen L

2014-01-01

Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg) is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others who have to rely on health-care professionals for their daily insulin injections. Further studies are required to confirm whether this might benefit adherence to treatment, reduce long-term

[Continuous subcutaneous insulin infusion in children less than 6 years-old: long-term progress].

Science.gov (United States)

Colino, Esmeralda; Martín Frías, María; Roldán, Belén; Álvarez, María Ángeles; Yelmo, Rosa; Barrio, Raquel

2017-11-01

The aims of the study are to evaluate the efficacy and safety of continuous subcutaneous insulin infusion (CSII) treatment in pre-school children with type I diabetes, and to assess whether the criteria of good metabolic control are achieved. A review was performed on the medical charts of patient's180mg/dl), and hypoglycaemia (<70mg/dl), mean blood glucose, standard deviation and coefficient of variation (SD/mean glucose ×100). Statistical analysis was performed using SPSS. HbA1c decreased from 6.9% (6.7-7.5) to 6.8% (6.4-7.1) after one year of CSII. Afterwards, it remained under 6.8% during the follow-up (median 5 years [3-6]). Prior to CSII, 74% of children had HbA1c levels < 7.5%. It increased to 96% after one year of CSII. Median blood glucose measurements /day was 10 (9-11). Total insulin dose did not change significantly. During the follow-up, there was one episode of DKA and one episode of HS. I/HC at breakfast were higher than at other meals (0.92 vs. 0.55, 0.6 and 0.5, respectively). CSII is effective and safe in pre-school children. It allows good metabolic control (based on Society for Paediatric and Adolescent Diabetes / American Diabetes Association criteria) to be achieved and maintained for long periods of time without an increase in adverse events. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Comparison of insulin intensification strategies with insulin lispro low mixture twice daily versus basal insulin glargine and prandial insulin lispro once daily in East Asian and Caucasian patients with type 2 diabetes mellitus.

Science.gov (United States)

Jeong, In-Kyung; Chung, Choon Hee; Zhou, Zhiguang; Han, Jeong Hee; Duan, Ran; Edralin, Diana M; Rodriguez, Angel

2017-04-01

This analysis evaluated efficacy and safety of insulin lispro low mixture (LM25) twice daily (breakfast and dinner) versus basal insulin glargine (bedtime) plus prandial insulin lispro (IGL) once daily before the largest meal in East Asian (EA) and Caucasian patients with type 2 diabetes mellitus who failed to reach glycemic targets on basal insulin glargine with metformin and/or pioglitazone. Included patients had an HbA1c ≥7.5% and ≤10.5% and fasting plasma glucose ≤6.7 mmol/L. Primary outcome was HbA1c change at 24 weeks. Baseline mean HbA1c was numerically similar between groups in EA (n = 79) and Caucasian (n = 278) patients. Mean (± SD) HbA1c decreased significantly from baseline to 24 weeks for LM25 and IGL in both subpopulations (EA: -1.32 ± 0.96% and -0.89 ± 0.96%; Caucasian: -1.24 ± 0.98% and -1.04 ± 0.97; all P 1). The respective proportions reaching HbA1c ≤7.0% at Week 24 in the LM25 and IGL groups were 33.3% and 22.9% (EA) and 37.2% and 34.1% (Caucasian). Mean (± SD) rates of hypoglycemia per 30 days in the LM25 and IGL groups were 0.74 ± 1.16 and 1.22 ± 1.36 (EA) and 1.38 ± 2.04 and 1.65 ± 2.43 (Caucasian). Mean (± SD) weight gain changes in the LM25 and IGL groups were 0.62 ± 2.78 and 0.51 ± 2.63 kg (EA) and 1.77 ± 2.91 and 0.67 ± 3.09 kg (Caucasian). Both strategies improved glycemic control in a small group of EA and Caucasian patients not adequately controlled on insulin glargine plus metformin and/or pioglitazone. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Long-term rates of mitochondrial protein synthesis are increased in mouse skeletal muscle with high-fat feeding regardless of insulin-sensitizing treatment.

Science.gov (United States)

Newsom, Sean A; Miller, Benjamin F; Hamilton, Karyn L; Ehrlicher, Sarah E; Stierwalt, Harrison D; Robinson, Matthew M

2017-11-01

Skeletal muscle mitochondrial protein synthesis is regulated in part by insulin. The development of insulin resistance with diet-induced obesity may therefore contribute to impairments to protein synthesis and decreased mitochondrial respiration. Yet the impact of diet-induced obesity and insulin resistance on mitochondrial energetics is controversial, with reports varying from decreases to increases in mitochondrial respiration. We investigated the impact of changes in insulin sensitivity on long-term rates of mitochondrial protein synthesis as a mechanism for changes to mitochondrial respiration in skeletal muscle. Insulin resistance was induced in C57BL/6J mice using 4 wk of a high-fat compared with a low-fat diet. For 8 additional weeks, diets were enriched with pioglitazone to restore insulin sensitivity compared with nonenriched control low-fat or high-fat diets. Skeletal muscle mitochondrial protein synthesis was measured using deuterium oxide labeling during weeks 10-12 High-resolution respirometry was performed using palmitoyl-l-carnitine, glutamate+malate, and glutamate+malate+succinate as substrates for mitochondria isolated from quadriceps. Mitochondrial protein synthesis and palmitoyl- l-carnitine oxidation were increased in mice consuming a high-fat diet, regardless of differences in insulin sensitivity with pioglitazone treatment. There was no effect of diet or pioglitazone treatment on ADP-stimulated respiration or H 2 O 2 emission using glutamate+malate or glutamate+malate+succinate. The results demonstrate no impairments to mitochondrial protein synthesis or respiration following induction of insulin resistance. Instead, mitochondrial protein synthesis was increased with a high-fat diet and may contribute to remodeling of the mitochondria to increase lipid oxidation capacity. Mitochondrial adaptations with a high-fat diet appear driven by nutrient availability, not intrinsic defects that contribute to insulin resistance. Copyright © 2017 the

Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance

DEFF Research Database (Denmark)

Breum, Leif; Bjerre, U; Bak, J F

1995-01-01

differences (mean +/- SD: F, 10.1 +/- 10.0 kg; P, 9.4 +/- 11.5 kg). Fifteen patients from the F group and 14 from the P group completed the 12-month study without weight loss differences. Glycemic regulation improved along with the weight loss, but with a larger decline in plasma C-peptide and fasting glucose......Fluoxetine (F) is a specific serotonin-reuptake inhibitor that has been shown to promote weight loss and improve glycemic control in obese diabetic patients. To study its long-term metabolic effect, 40 obese patients with non-insulin -dependent diabetes mellitus (NIDDM) or impaired glucose...... tolerance (IGT) were included in a 12-month, randomized, placebo controlled study. Patients were assigned to receive either 60 mg F or placebo (P) daily in conjunction with a 5.0-MJ/d diet (> 50% carbohydrate). Both groups showed a significant weight loss, with a nadir after 6 months without group...

Continuous subcutaneous insulin infusion (CSII) therapy at Derby Teaching Hospitals: sustained benefits in glucose control.

Science.gov (United States)

Anyanwagu, U; Olaoye, H; Jennings, P; Ashton-Cleary, S; Sugunendran, S; Hughes, D; Idris, I; Wilmot, E G

2017-08-01

In the short term, continuous subcutaneous insulin infusion (CSII) has been associated with improved glycaemic control, reduced hypoglycaemia and improved quality of life (QOL). However, limited data are available on its long-term benefits, particularly in the UK. We aimed to assess the impact of CSII on longer term outcomes. Patient-level data were obtained for CSII users at Derby Teaching Hospitals, UK. Patient confidence and satisfaction questionnaires using the Likert scale were used to assess confidence in self-management. Comparative statistics were conducted using Pearson's chi-square and Student's t-tests. Some 258 CSII users were identified (60.1% female, mean age 43.9 ± 13.4 years). Overall, there was significant decrease in HbA 1c from 78 mmol/mol (9.3 ± 2.0%) at baseline, to 69 mmol/mol (8.5 ± 1.3%) at 6 months [mean difference (md): -0.64; 95% confidence interval (95% CI): -0.91 to -0.37; P quality of care received in the insulin pump service. CSII therapy led to a sustained long-term improvement in glycaemic control in addition to a reduction in self-reported hypoglycaemia. © 2017 Diabetes UK.

The short term effect of insulin, metformin and insulin-metformin combination on the liver morphology in high fat diet/streptozotocin induced diabetic albino rats

International Nuclear Information System (INIS)

Mubeen, S.; Amjad, Z.; Memon, F.M.

2016-01-01

Objective: To evaluate the histological effects of insulin, metformin and insulin-metformin combination on liver morphology in high fat diet (HFD) / Streptozotocin (STZ) induced diabetic albino rats. Study Design: Experimental and comparative study. Place and Duration of Study: Institute of Basic Medical Sciences (IBMS), Dow University of Health Sciences (DUHS), Ojha Campus, Karachi, from January to August 2012. Methodology: The study was conducted on 50 HFD/STZ induced diabetic albino wistar rats which were randomized into 5 groups. One of the groups was treated with insulin, one with metformin, and the other group with insulin-metformin combination for 4 weeks. One of the groups was left untreated. One group was control group. After the treatment period, the rats were sacrificed and livers were isolated, weighed, processed and stained to analyse the difference in hepatic morphology in each treated and untreated groups, then the results were compared with control rats. Results: Statistically significant difference (p < 0.0001) was seen between the groups by using Kruskill Wallis Test. To further investigate the effectiveness of insulin, metformin and insulin-metformin combination, Mann-Whitney U-test was applied. Statistically significant difference was noticed when diabetic rats were given insulin-metformin combination (p < 0.0001). Conclusion: The combination therapy was observed to have better effects on liver morphology than insulin and metformin used separately. (author)

PROXIMITY TO DELIVERY ALTERS INSULIN SENSITIVITY AND GLUCOSE METABOLISM IN PREGNANT MICE

OpenAIRE

Musial, Barbara; Fernandez-Twinn, Denise S.; Vaughan, Owen R.; Ozanne, Susan E.; Voshol, Peter; Sferruzzi-Perri, Amanda N.; Fowden, Abigail L.

2016-01-01

In late pregnancy, maternal insulin resistance occurs to support fetal growth but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy, day (D) 16, and near term, D19, (term 20.5D). Non-pregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by dual energy X-ray absorptiometry, tissue insulin signalling protein abundance by Western blotting, glucose tolerance and ut...

27 CFR 25.11 - Meaning of terms.

Science.gov (United States)

2010-04-01

.... The product of brewing before fermentation which results in beer. [T.D. ATF-224, 51 FR 7673, Mar. 5... OF THE TREASURY LIQUORS BEER Definitions § 25.11 Meaning of terms. When used in this part, where not... 27 CFR Part 25, Beer. Balling. The percent by weight of dissolved solids at 60 °F. present in wort...

Carbohydrate-to-insulin ratio is estimated from 300-400 divided by total daily insulin dose in type 1 diabetes patients who use the insulin pump.

Science.gov (United States)

Kuroda, Akio; Yasuda, Tetsuyuki; Takahara, Mitsuyoshi; Sakamoto, Fumie; Kasami, Ryuichi; Miyashita, Kazuyuki; Yoshida, Sumiko; Kondo, Eri; Aihara, Ken-ichi; Endo, Itsuro; Matsuoka, Taka-aki; Kaneto, Hideaki; Matsumoto, Toshio; Shimomura, Iichiro; Matsuhisa, Munehide

2012-11-01

To optimize insulin dose using insulin pump, basal and bolus insulin doses are widely calculated from total daily insulin dose (TDD). It is recommended that total daily basal insulin dose (TBD) is 50% of TDD and that the carbohydrate-to-insulin ratio (CIR) equals 500 divided by TDD. We recently reported that basal insulin requirement is approximately 30% of TDD. We therefore investigated CIR after adjustment of the proper basal insulin rate. Forty-five Japanese patients with type 1 diabetes were investigated during several weeks of hospitalization. The patients were served standard diabetes meals (25-30 kcal/kg of ideal body weight). Each meal omission was done to confirm basal insulin rate. Target blood glucose level was set at 100 and 150 mg/dL before and 2 h after each meal, respectively. After the basal insulin rate was fixed and target blood glucose levels were achieved, TBD, CIR, TDD, and their products were determined. Mean (±SD) blood glucose levels before and 2 h after meals were 121±47 and 150±61 mg/dL, respectively. TDD was 31.5±9.0 U, and TBD was 27.0±6.5% of TDD. CIR×TDD of breakfast was significantly lower than those of lunch and supper (288±73 vs. 408±92 and 387±83, respectively; Plunch and supper in type 1 diabetes patients. These results indicate that the insulin dose has been underestimated by using previously established calculations.

[Hypertension and insulin treatment in type 2 diabetes].

Science.gov (United States)

Ben Salem Hachmi, L; Bouguerra, R; Maatki, O; Smadhi, H; Turki, Z; Hraoui, S; Ben Slama, C

2007-08-01

Insulin resistance and endogenous hyperinsulinemia are associated with blood hypertension. The aim of this analysis is to estimate the prevalence of blood hypertension one year after insulin treatment in type 2 diabetic patients. and methods: This is a retrospective clinical study of 178 type 2 diabetic patients (57 men and 121 women) insulin treated since at least one year. Mean age is 62 +/- 10 years and mean duration of diabetes is ten years. All patients had a clinical and biological control before treatment with insulin and at least three controls during the first year of insulin treatment (anthropometric measurements, blood pressure, fasting plasma glucose, HbA1C). WHO definition of hypertension is used (blood pressure >or=140 / 90 mmHg). At baseline, 48% of patients have hypertension. After insulin treatment, the prevalence of hypertension significantly increase to 53% (94 / 178) three months later (p=0.008), to 54.5% (98 / 178) six months later (p=0.001) and to 55.6% (99 / 178) twelve months later. This increase in hypertension frequency is associated with a significant weight gain and a better blood glucose control. Insulin therapy may contribute to the development of blood hypertension. It promotes renal sodium retention and increases sympathetic nervous system activity. In the UKPDS intensive blood glucose control with insulin is not associated with an increase of macro vascular complications. These observational data suggest the need for further study of the relationship between exogenous insulin and hypertension.

Hepatic Insulin Resistance and Altered Gluconeogenic Pathway in Premature Baboons.

Science.gov (United States)

McGill-Vargas, Lisa; Gastaldelli, Amalia; Liang, Hanyu; Anzueto Guerra, Diana; Johnson-Pais, Teresa; Seidner, Steven; McCurnin, Donald; Muscogiuri, Giovanna; DeFronzo, Ralph; Musi, Nicolas; Blanco, Cynthia

2017-05-01

Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extrauterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content, and gene expression of key insulin-signaling/gluconeogenic molecules. Fetal baboons were delivered at 67%, 75%, and term gestational age and euthanized at birth. Neonatal baboons were delivered prematurely (67% gestation), survived for two weeks, and compared with similar postnatal term animals and underwent serial hyperinsulinemic-euglycemic clamp studies. Premature baboons had decreased endogenous glucose production (EGP) compared with term animals. Consistent with these results, the gluconeogenic molecule, phosphoenolpyruvate carboxykinase messenger RNA, was decreased in preterm baboons compared with terms. Hepatic insulin signaling was altered by preterm birth as evidenced by decreased insulin receptor-β, p85 subunit of phosphoinositide 3-kinase, phosphorylated insulin receptor substrate 1, and Akt-1 under insulin-stimulated conditions. Furthermore, preterm baboons failed to have the normal increase in glycogen synthase kinase-α from fetal to postnatal life. The blunted responses in hepatic insulin signaling may contribute to the hyperglycemia of prematurity, while impaired EGP leads to hypoglycemia of prematurity. Copyright © 2017 Endocrine Society.

Identification of metformin poor responders, requiring supplemental insulin, during randomization of metformin versus insulin for the control of gestational diabetes mellitus.

Science.gov (United States)

Ashoush, Sherif; El-Said, Mourrad; Fathi, Hisham; Abdelnaby, Mohamed

2016-06-01

To evaluate glycemic control among women with gestational diabetes mellitus (GDM) under insulin versus metformin (with or without insulin supplementation), and to identify metformin poor responders requiring supplemental insulin. In Ain Shams University Hospital, mothers with 26-32-week GDM pregnancies, failing diet control, were randomized to receive metformin (n = 47) or insulin (n = 48). The primary outcome was glycemic control. Secondary outcomes included maternal weight, parameters predicting successful metformin monotherapy, neonatal hypoglycemia, and birthweight. Women using metformin (23.4% needing supplemental insulin) gained less weight (P metformin group was related to initial body mass index, HbA1c, oral glucose tolerance test (GTT), and first week mean glucose level. The 1-h glucose level during initial GTT (Hr1-GTT) and the mean fasting glucose level during the first week of therapy (Wk1-mFG) were the two independent parameters associated with requiring supplemental insulin. Women with Hr1-GTT >212 mg/dL and Wk1-mFG >95 mg/dL had a risk ratio of 58.6 (95%CI: 3.68-933.35, P = 0.004) and 11.5 (95%CI: 2.77-47.34,= 0.0008), respectively for needing supplemental insulin during the course of the study compared with women without. Metformin is an effective and safe alternative to insulin in GDM. Women using metformin (± supplemental insulin) had similar glycemic control, less weight gain, and similar rates of side-effects as those on insulin monotherapy. Insulin supplementation to metformin therapy was more likely with elevated Hr1-GTT and Wk1-mFG. © 2016 Japan Society of Obstetrics and Gynecology.

Nutritional Modulation of Insulin Resistance

Directory of Open Access Journals (Sweden)

Martin O. Weickert

2012-01-01

Full Text Available Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM. Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss is generally difficult to achieve, and distinct metabolic characteristics in patients with T2DM further compromise success. Therefore, investigating the effects of modulating the macronutrient composition of isoenergetic diets is an interesting concept that may lead to additional important insights. Metabolic effects of various different dietary concepts and strategies have been claimed, but results from randomized controlled studies and particularly from longer-term-controlled interventions in humans are often lacking. However, some of these concepts are supported by recent research, at least in animal models and short-term studies in humans. This paper provides an update of the current literature regarding the role of nutrition in the modulation of insulin resistance, which includes the discussion of weight-loss-independent metabolic effects of commonly used dietary concepts.

The extended meanings of medical terms. Difficulties in the practice of translation

Directory of Open Access Journals (Sweden)

Corina Lungu

2015-10-01

Full Text Available Taking into account that the structure of a specialized field is never homogeneous, in order to interpret or translate a term, we should define and know its different possible "semantic manifestations" (Martin, 1972: 125. In order to facilitate understanding and to ensure translation accuracy, we analyze - from the perspective of an internal polysemy - the terms of the medical lexicon which constitute a specific and restrictive use of the common language lexicon. Through the study of a selection of terms extracted from a specialized dictionary (Dicţionar Medical, Rusu V. 2010, this communication illustrates the restrictions and the extensions of meaning in a double translation: the terms taken from the common language with a restrictive meaning in the specialized field; the terms belonging to related disciplines and various fields adopting a specific meaning in the medical area. All these directions of change of meaning are thus envisaged to facilitate the practice of translation which raises both general and specific difficulties.

The correlations between insulin-like growth factor I, insulin and gestational diabetes mellitus

International Nuclear Information System (INIS)

Xu Yongle; Yang Weiwen; Pu Xiangke

2006-01-01

Objectives; To research the correlation between insulin-like growth factor I (IGF-I), insulin and gestational diabetes mellitus (GDM). Methods: Thirty cases of GDM are taken as the GDM group. Thirty cases of normal pregnant women were taken as the control group. The insulin in maternal serum of these two groups were measured at 31 ± 1 weeks gestational age by radioimmunity. The IGF-I in maternal serum at 31 ± 1 weeks gestational age and IGF-I in umbilical serum at term delivery were measured by ELISA. results: There was no significant difference in IGF-I level in maternal serum between the GDM group and the control group (P>0.05) and there was significant difference between these two groups maternal LnIRI, IGF-I in umbilical serum and weight of newborn baby (P<0.01). In the GDM group, the IGF-I in maternal serum positively correlated with the LnIRI (r=0.424, P<0.05) and IGF-I in umbilical serum positively correlated with the weight of new-born baby (r=0.434, P<0.05). Conclusion: GDM has serious insulin resistance. The IGF-I in maternal serum correlated with the IR in GDM. IGF-I in umbilical serum plays a role in the pathology and physiology process of fetal macrosomia. Abnormality of the axis of growth hormone-insulin-insulin-like growth factor caused by IGF-I might be through the way of insulin resistance, and GDM is resulted. (authors)

Short-and long-term glucocorticoid treatment enhances insulin signalling in human subcutaneous adipose tissue

OpenAIRE

Gathercole, LL; Morgan, SA; Bujalska, IJ; Stewart, PM; Tomlinson, JW

2011-01-01

Background: Endogenous or exogenous glucocorticoid (GC) excess (Cushing's syndrome) is characterized by increased adiposity and insulin resistance. Although GCs cause global insulin resistance in vivo, we have previously shown that GCs are able to augment insulin action in human adipose tissue, contrasting with their action in skeletal muscle. Cushing's syndrome develops following chronic GC exposure and, in addition, is a state of hyperinsulinemia. Objectives: We have therefore compared the ...

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

Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.

Science.gov (United States)

Vinik, A I; Seino, S; Funakoshi, A; Schwartz, J; Matsumoto, M; Schteingart, D E; Fu, Z Z; Tsai, S T

1986-04-01

A 45-yr-old muscular nonobese white man who had a 9-yr history of syncopal episodes was studied on several occasions between April 1979 and August 1984. Fasting glucose concentrations ranged between 74-115 mg/dl, and those of insulin ranged between 14-64 microU/ml. Reactive hypoglycemia 3-4 h after ingestion of glucose occurred in the first 2 yr. Glucose tolerance was impaired in 1979, from February 1982 through September 1983, and again in August 1984. The maximum plasma insulin response to glucose ranged between 475-1630 microU/ml. When studied in November 1982, insulin (0.1 U/kg) caused a fall in blood glucose concentration of only 25% (normal, greater than 50%), and maximal glucose utilization during the euglycemic hyperinsulinemic clamp was 7.5 mg/kg . min (normal, greater than 12 mg/kg . min). Plasma counterregulatory hormone concentrations were normal, and antibodies to insulin and the insulin receptor were absent. Binding of exogenous insulin to the patient's cellular receptors (monocytes, red blood cells, and skin fibroblasts) was normal. Insulin was purified from plasma by immunoaffinity and molecular sieve chromatography and was found to elute later than human insulin on reversed phase high performance liquid chromatography. It was more hydrophobic than normal human insulin and had only 10% of the activity of normal insulin in terms of ability to bind to and stimulate glucose metabolism in isolated rat adipocytes. The abnormal insulin was identified in two of three sons and a sister, but not in the mother, brother, or niece. Sensitivity to insulin was normal in the two sons who had abnormal insulin. These results suggest that in this family the abnormal insulin was due to a biosynthetic defect, inherited as an autosomal dominant trait. The hyperinsulinemia was not associated with diabetes in family members who had no insulin resistance.

Comparison of Subcutaneous Regular Insulin and Lispro Insulin in Diabetics Receiving Continuous Nutrition: A Numerical Study.

Science.gov (United States)

Stull, Mamie C; Strilka, Richard J; Clemens, Michael S; Armen, Scott B

2015-06-30

Optimal management of non-critically ill patients with diabetes maintained on continuous enteral feeding (CEN) is poorly defined. Subcutaneous (SQ) lispro and SQ regular insulin were compared in a simulated type 1 and type 2 diabetic patient receiving CEN. A glucose-insulin feedback mathematical model was employed to simulate type 1 and type 2 diabetic patients on CEN. Each patient received 25 SQ injections of regular insulin or insulin lispro, ranging from 0-6 U. Primary endpoints were the change in mean glucose concentration (MGC) and change in glucose variability (GV); hypoglycemic episodes were also reported. The model was first validated against patient data. Both SQ insulin preparations linearly decreased MGC, however, SQ regular insulin decreased GV whereas SQ lispro tended to increase GV. Hourly glucose concentration measurements were needed to capture the increase in GV. In the type 2 diabetic patient, "rebound hyperglycemia" occurred after SQ lispro was rapidly metabolized. Although neither SQ insulin preparation caused hypoglycemia, SQ lispro significantly lowered MGC compared to SQ regular insulin. Thus, it may be more likely to cause hypoglycemia. Analyses of the detailed glucose concentration versus time data suggest that the inferior performance of lispro resulted from its shorter duration of action. Finally, the effects of both insulin preparations persisted beyond their duration of actions in the type 2 diabetic patient. Subcutaneous regular insulin may be the short-acting insulin preparation of choice for this subset of diabetic patients. Clinical trial is required before a definitive recommendation can be made. © 2015 Diabetes Technology Society.

Fasting glucose, fasting insulin, and insulin resistance in the prediction of myocardial infarction and mortality at long-term follow-up

DEFF Research Database (Denmark)

Nielsen, M. L.; Pareek, M.; Leosdottir, M.

2015-01-01

Objective: To assess the additional prognostic value of fasting blood glucose (FBG), fasting plasma insulin (FPI), and homeostasis model assessment derived insulin resistance (HOMA-IR) for predicting incident myocardial infarction (MI) and all-cause mortality, independently of traditional...... measured at baseline. Subsequently, HOMA-IR was derived using the computerized HOMA calculator and ranked into quartiles due to the non-normal distribution and presumably non-linear biological effect of insulin resistance. Prognostic values of FBG, FPI, HOMA-IR, and traditional risk factors were tested.......1-48.3] years, whereas median [IQR] HOMA-IR was 0.9 [0.4-1.4]. Over a median follow-up time of 20 years, 1448 events occurred (11.3 per 1000 person-years). The simple prediction model, i.e. the model with traditional CV risk factors only, included age, gender, body mass index, systolic blood pressure, total...

Insulin receptor degradation is accelerated in cultured lymphocytes from patients with genetic syndromes of extreme insulin resistance

International Nuclear Information System (INIS)

McElduff, A.; Hedo, J.A.; Taylor, S.I.; Roth, J.; Gorden, P.

1984-01-01

The insulin receptor degradation rate was examined in B lymphocytes that were obtained from peripheral blood of normal subjects and patients with several syndromes of extreme insulin resistance. The insulin receptors were surface labeled using Na 125 I/lactoperoxidase and the cells were returned to incubate in growth media. After varying periods of incubation, aliquots of cells were solubilized and the cell content of labeled receptor subunits were measured by immunoprecipitation with anti-receptor antibodies and NaDodSO4/polyacrylamide gel electrophoresis. In cell lines from four patients in whom the number of insulin receptors was reduced by greater than 90%, the rate of receptor loss was greater than normal (t1/2 equals 3.8 +/- 0.9 h vs. 6.5 +/- 1.2 h; mean +/- SD, P less than 0.01). However, a similar acceleration in receptor degradation was seen in cells from five patients with extreme insulin resistance but low-normal insulin receptor concentration (t1/2 equals 4.4 +/- 0.9 h). Thus, all the patients with genetic syndromes of insulin resistance had accelerated receptor degradation, regardless of their receptor concentration. By contrast, insulin receptors on cultured lymphocytes that were obtained from patients with extreme insulin resistance secondary to autoantibodies to the insulin receptor had normal receptor degradation (t1/2 equals 6.1 +/- 1.9 h). We conclude that (a) accelerated insulin receptor degradation is an additional feature of cells from patients with genetic forms of insulin resistance; (b) that accelerated insulin receptor degradation may explain the low-normal receptor concentrations that were seen in some patients with extreme insulin resistance; and (c) that accelerated degradation does not explain the decreased receptor concentration in patients with very low insulin receptor binding and, therefore, by inference, a defect in receptor synthesis must be present in this subgroup

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

Science.gov (United States)

Baillargeon, Jean-Patrice; Carpentier, André

2007-10-01

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

Long-term effects of continuous subcutaneous infusion versus daily subcutaneous injections of growth hormone (GH) on the insulin-like growth factor system, insulin sensitivity, body composition, and bone and lipoprotein metabolism in GH-deficient adults

DEFF Research Database (Denmark)

Laursen, Torben; Gravholt, Claus Højbjerg; Heickendorff, Lene

2001-01-01

injections (inj) in the evening as usual, and 7 received a continuous infusion (inf) of GH by means of a portable pump. The GH dose was kept unchanged before and during the study. Serum levels of insulin-like growth factor I (IGF-I) tended to increase in the patients switched to constant infusion (from 175...... for 6 months are comparable with respect to the IGF-IGFBP axis, whereas intermittent exposure may be of importance for the lipolytic effect of GH. The data on insulin sensitivity and lipoproteins suggest that constant GH exposure is as safe as intermittent GH administration....

Insulin initiation status of primary care physicians in Turkey, barriers to insulin initiation and knowledge levels about insulin therapy: A multicenter cross-sectional study.

Science.gov (United States)

Ates, Elif; Set, Turan; Saglam, Zuhal; Tekin, Nil; Karatas Eray, Irep; Yavuz, Erdinc; Sahin, Mustafa Kursat; Selcuk, Engin Burak; Cadirci, Dursun; Cubukcu, Mahcube

2017-10-01

Our aim was to evaluate the insulin initiation status, barriers to insulin initiation and knowledge levels about treatment administered by primary care physicians (PCP). We conducted our study in accordance with a multicenter, cross-sectional design in Turkey, between July 2015 and July 2016. A questionnaire inquiring demographic features, status of insulin initiation, obstacles to insulin initiation and knowledge about therapy of the PCPs was administered during face-to-face interviews. 84 PCPs (19%) (n=446, mean age=41.5±8.4years, 62.9% male and 90.0% ministry certified family physicians) initiated insulin therapy in the past. Most of the stated primary barriers (51.9%, n=230) were due to the physicians. The most relevant barrier was "lack of clinical experience" with a rate of 19% (n=84 of the total). The average total knowledge score was 5.7±2.0 for the family medicine specialist, and 3.8±2.1 for the ministry certified family physicians (p=0.000, maximum knowledge score could be 10). The status of insulin initiation in Turkey by the primary care physicians is inadequate. Medical education programs and health care systems may require restructuring to facilitate insulin initiation in primary care. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Cancer risk among insulin users

DEFF Research Database (Denmark)

But, Anna; De Bruin, Marie L.; Bazelier, Marloes T.

2017-01-01

Aims/hypothesis: The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies. Methods: National Health Registries from Denmark (1996–2010), Finland (1996–2011), Norway (2005......–2010) and Sweden (2007–2012) and the UK Clinical Practice Research Datalink database (1987–2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression...... models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5–1, 1–2, 2–3, 3–4, 4–5, 5–6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin. Results: A total of 21,390 cancer cases occurred during a mean...

Influence of insulin therapy on circulating ghrelin and insulin-like ghrelinowth factor-1(IGF-1) levels in children with type-1 diabetes mellitus

International Nuclear Information System (INIS)

Moawad, A.T.; Nassar, E.M.; Mostafa, A.M.; Mohammed, S.K.

2009-01-01

Diabetes mellitus type 1 (IDDM)is a chronic disease associated with alterations in the growth hormone/insulin -like growth factor (GH-IGF) system and ghrelin level which may lead to changes in metabolic control. This study aimed to evaluate the circulating levels of the gut-derived peptides (ghrelin and insulin-like growth factors (IGF s ) in children with IDDM and to link these two peptides with the glucose level in diabetic children at diagnoses and after insulin therapy. Design and methods: the studied group consisted of 30 newly diagnosed diabetic children (17 females and 13 males) diagnosed in paediatric diabetes unit, children's hospital, Ain shams university. Their age ranged from (6.2-11.8) years with mean of 10.10± 1.74 years. Twenty non diabetic healthy children matching in age and sex served as controls. Serum ghrelin was determined by enzyme linked immuno absorbanet assay (ELISA), while IGF-1 and insulin-like growth factors binding proteins -1 and 3 (IGFBP s ) were assessed by radioimmunoassay(RIA). Results: body mass index (BMI) in patients was significantly decreased in the diabetic group as compared to the healthy group at diagnosis. After insulin therapy BMI was significantly increase as compared to its value at diagnosis (p< 0.05) such increase was not significant on comparing to controls. Regarding blood glucose level there was very highly significant decrease in the level of HBAI (glycolated HB) in diabetic patients after insulin therapy (p<0.0001) than at diagnosis . The mean ghrelin level was highly significantly decreased in diabetic children at diagnosis and after insulin therapy as compared to controls (p<0.0001). No differences were found in the mean ghrelin levels in diabetic children at diagnosis or after insulin therapy.conclusions : the decrease in mean gherlin levels in this study at diagnosis and after therapy could reflect an attempt by the body to decrease the glucose level and thus may prevent hyperglycemia in diabetic patients

Insulin signaling in various equine tissues under basal conditions and acute stimulation by intravenously injected insulin.

Science.gov (United States)

Warnken, Tobias; Brehm, Ralph; Feige, Karsten; Huber, Korinna

2017-10-01

The aim of the study was to analyze key proteins of the equine insulin signaling cascade and their extent of phosphorylation in biopsies from muscle tissue (MT), liver tissue (LT), and nuchal AT, subcutaneous AT, and retroperitoneal adipose tissues. This was investigated under unstimulated (B1) and intravenously insulin stimulated (B2) conditions, which were achieved by injection of insulin (0.1 IU/kg bodyweight) and glucose (150 mg/kg bodyweight). Twelve warmblood horses aged 15 ± 6.8 yr (yr), weighing 559 ± 79 kg, and with a mean body condition score of 4.7 ± 1.5 were included in the study. Key proteins of the insulin signaling cascade were semiquantitatively determined using Western blotting. Furthermore, modulation of the cascade was assessed. The basal expression of the proteins was only slightly influenced during the experimental period. Insulin induced a high extent of phosphorylation of insulin receptor in LT (P < 0.01) but not in MT. Protein kinase B and mechanistic target of rapamycin expressed a higher extent of phosphorylation in all tissues in B2 biopsies. Adenosine monophosphate protein kinase, as a component related to insulin signaling, expressed enhanced phosphorylation in MT (P < 0.05) and adipose tissues (nuchal AT P < 0.05; SCAT P < 0.01; retroperitoneal adipose tissue P < 0.05), but not in LT at B2. Tissue-specific variations in the acute response of insulin signaling to intravenously injected insulin were observed. In conclusion, insulin sensitivity in healthy horses is based on a complex concerted action of different tissues by their variations in the molecular response to insulin. Copyright © 2017 Elsevier Inc. All rights reserved.

Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study.

Science.gov (United States)

Peyrot, M; Barnett, A H; Meneghini, L F; Schumm-Draeger, P-M

2012-05-01

To examine patient and physician beliefs regarding insulin therapy and the degree to which patients adhere to their insulin regimens. Internet survey of 1250 physicians (600 specialists, 650 primary care physicians) who treat patients with diabetes and telephone survey of 1530 insulin-treated patients (180 with Type 1 diabetes, 1350 with Type 2 diabetes) in China, France, Japan, Germany, Spain, Turkey, the UK or the USA. One third (33.2%) of patients reported insulin omission/non-adherence at least 1 day in the last month, with an average of 3.3 days. Three quarters (72.5%) of physicians report that their typical patient does not take their insulin as prescribed, with a mean of 4.3 days per month of basal insulin omission/non-adherence and 5.7 days per month of prandial insulin omission/non-adherence. Patients and providers indicated the same five most common reasons for insulin omission/non-adherence: too busy; travelling; skipped meals; stress/emotional problems; public embarrassment. Physicians reported low patient success at initiating insulin in a timely fashion and adjusting insulin doses. Most physicians report that many insulin-treated patients do not have adequate glucose control (87.6%) and that they would treat more aggressively if not for concern about hypoglycaemia (75.5%). Although a majority of patients (and physicians) regard insulin treatment as restrictive, more patients see insulin treatment as having positive than negative impacts on their lives. Glucose control is inadequate among insulin-treated patients, in part attributable to insulin omission/non-adherence and lack of dose adjustment. There is a need for insulin regimens that are less restrictive and burdensome with lower risk of hypoglycaemia. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Insulin inhalation for diabetic patients: Nursing considerations

Directory of Open Access Journals (Sweden)

Hanan Mohammed Mohammed

2016-04-01

Full Text Available Scientific knowledge has advanced to enable the development of inhaled insulin. It is a form of diabetes medication administered via the pulmonary system that studies have shown to be efficacious in the treatment of both type 1 and type 2 diabetes. Inhaled insulin is a new, safe means to deliver insulin that may increase patient compliance with insulin therapy, helping them to achieve optimal glycemic control and possibly reducing their risk of developing cardiovascular complications. However, diabetes is a chronic illness requiring lifetime intervention. Empowering patients with the knowledge of the diabetes disease process may give them the confidence to be more autonomous in managing their diabetes. HIIP gives nurse practitioners a new option that may improve their patients’ acceptance of insulin therapy, and improve glycemic control.

UV-light exposure of insulin: pharmaceutical implications upon covalent insulin dityrosine dimerization and disulphide bond photolysis.

Science.gov (United States)

Correia, Manuel; Neves-Petersen, Maria Teresa; Jeppesen, Per Bendix; Gregersen, Søren; Petersen, Steffen B

2012-01-01

In this work we report the effects of continuous UV-light (276 nm, ~2.20 W.m(-2)) excitation of human insulin on its absorption and fluorescence properties, structure and functionality. Continuous UV-excitation of the peptide hormone in solution leads to the progressive formation of tyrosine photo-product dityrosine, formed upon tyrosine radical cross-linkage. Absorbance, fluorescence emission and excitation data confirm dityrosine formation, leading to covalent insulin dimerization. Furthermore, UV-excitation of insulin induces disulphide bridge breakage. Near- and far-UV-CD spectroscopy shows that UV-excitation of insulin induces secondary and tertiary structure losses. In native insulin, the A and B chains are held together by two disulphide bridges. Disruption of either of these bonds is likely to affect insulin's structure. The UV-light induced structural changes impair its antibody binding capability and in vitro hormonal function. After 1.5 and 3.5 h of 276 nm excitation there is a 33.7% and 62.1% decrease in concentration of insulin recognized by guinea pig anti-insulin antibodies, respectively. Glucose uptake by human skeletal muscle cells decreases 61.7% when the cells are incubated with pre UV-illuminated insulin during 1.5 h. The observations presented in this work highlight the importance of protecting insulin and other drugs from UV-light exposure, which is of outmost relevance to the pharmaceutical industry. Several drug formulations containing insulin in hexameric, dimeric and monomeric forms can be exposed to natural and artificial UV-light during their production, packaging, storage or administration phases. We can estimate that direct long-term exposure of insulin to sunlight and common light sources for indoors lighting and UV-sterilization in industries can be sufficient to induce irreversible changes to human insulin structure. Routine fluorescence and absorption measurements in laboratory experiments may also induce changes in protein

UV-light exposure of insulin: pharmaceutical implications upon covalent insulin dityrosine dimerization and disulphide bond photolysis.

Directory of Open Access Journals (Sweden)

Manuel Correia

Full Text Available In this work we report the effects of continuous UV-light (276 nm, ~2.20 W.m(-2 excitation of human insulin on its absorption and fluorescence properties, structure and functionality. Continuous UV-excitation of the peptide hormone in solution leads to the progressive formation of tyrosine photo-product dityrosine, formed upon tyrosine radical cross-linkage. Absorbance, fluorescence emission and excitation data confirm dityrosine formation, leading to covalent insulin dimerization. Furthermore, UV-excitation of insulin induces disulphide bridge breakage. Near- and far-UV-CD spectroscopy shows that UV-excitation of insulin induces secondary and tertiary structure losses. In native insulin, the A and B chains are held together by two disulphide bridges. Disruption of either of these bonds is likely to affect insulin's structure. The UV-light induced structural changes impair its antibody binding capability and in vitro hormonal function. After 1.5 and 3.5 h of 276 nm excitation there is a 33.7% and 62.1% decrease in concentration of insulin recognized by guinea pig anti-insulin antibodies, respectively. Glucose uptake by human skeletal muscle cells decreases 61.7% when the cells are incubated with pre UV-illuminated insulin during 1.5 h. The observations presented in this work highlight the importance of protecting insulin and other drugs from UV-light exposure, which is of outmost relevance to the pharmaceutical industry. Several drug formulations containing insulin in hexameric, dimeric and monomeric forms can be exposed to natural and artificial UV-light during their production, packaging, storage or administration phases. We can estimate that direct long-term exposure of insulin to sunlight and common light sources for indoors lighting and UV-sterilization in industries can be sufficient to induce irreversible changes to human insulin structure. Routine fluorescence and absorption measurements in laboratory experiments may also induce changes

Four-year evolution of insulin regimens, glycaemic control, hypoglycaemia and body weight after starting insulin therapy in type 2 diabetes across three continents.

Science.gov (United States)

Home, Philip D; Dain, Marie-Paule; Freemantle, Nick; Kawamori, Ryuzo; Pfohl, Martin; Brette, Sandrine; Pilorget, Valérie; Scherbaum, Werner A; Vespasiani, Giacomo; Vincent, Maya; Balkau, Beverley

2015-05-01

It is of interest to understand how insulin therapy currently evolves in clinical practice, in the years after starting insulin in people with type 2 diabetes. We aimed to describe this evolution prospectively over 4 years, to assist health care planning. People who had started any insulin were identified from 12 countries on three continents. Baseline, then yearly follow-up, data were extracted from clinical records over 4 years. Of the 2999 eligible people, 2272 were followed over 4 years. When starting insulin, mean (SD) duration of diabetes was 10.6 (7.8) years, HbA1c 9.5 (2.0)% (80 [22]mmol/mol) and BMI 29.3 (6.3)kg/m(2). Initial insulin therapy was basal 52%, premix 23%, mealtime+basal 14%, mealtime 8% and other 3%; at 4 years, 30%, 25%, 33%, 2% and 5%, respectively, with 5% not on insulin. Insulin dose was 20.2U/day at the start and 45.8U/day at year 4. There were 1258 people (55%) on their original regimen at 4 years, and this percentage differed according to baseline insulin regimen. HbA1c change was -2.0 (2.2)% (-22 [24]mmol/mol) and was similar by final insulin regimen. Hypoglycaemia prevalence was <20% in years 1-4. Body weight change was mostly in year 1, and was very variable, mean +2.7 (7.5)kg at year 4. Different insulin regimens were started in people with differing characteristics, and they evolved differently; insulin dose, hypoglycaemia and body weight change were diverse and largely independent of regimen. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Studies on insulin receptor, 2

International Nuclear Information System (INIS)

Sakai, Yukio

1979-01-01

The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using 125 I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and 125 I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia. (author)

Polymorphonuclear leucocyte dysfunction during short term metabolic changes from normo- to hyperglycemia in type 1 (insulin dependent) diabetic patients

DEFF Research Database (Denmark)

Kjersem, H; Hilsted, J; Madsbad, S

1988-01-01

Polymorphonuclear leucocyte (PMN) ingestion of particles coated with lipopolysaccharide (LPS) from Escherichia coli was compared to other PMN functions in seven patients with insulin dependent diabetes mellitus (IDDM) during short-term controlled metabolic changes from normo- to hyperglycemia...... without ketoacidosis. Factors known to interfere with PMN functions were excluded. PMN ingestion of particles coated with both LPS and bovine serum albumin became reduced from normo- to hyperglycemia. PMN motility was impaired in IDDM, but did not seem to be affected by short-term changes in metabolic...... control. PMN metabolism did not change from normo-to hyperglycemia. Particle-uptake by diabetic PMN is impaired after short term hyperglycemia in the range normally occurring in diabetics in every-day life....

Long-term tolerability of inhaled human insulin (Exubera) in patients with poorly controlled type 2 diabetes

DEFF Research Database (Denmark)

Barnett, A H; Lange, P; Dreyer, M

2007-01-01

or metformin (study 1) and patients poorly controlled on metformin were randomised to adjunctive EXU or the sulphonylurea, glibenclamide (study 2). PATIENTS: The studies included 446 (study 1) and 476 (study 2) patients with type 2 diabetes, no clinically significant respiratory disease and glycosylated....... There was no discernable effect of long-term EXU therapy on pulmonary gas exchange. Insulin antibody binding reached a plateau at 6 months and did not correlate with HbA(1c) or lung function changes. Glycaemic control was maintained over 2 years. CONCLUSIONS: Exubera was well tolerated during long-term use. Pulmonary...... function changes compared with comparator groups were small, non-progressive and reversed upon treatment discontinuation. Importantly, rates of lung function change were indistinguishable between EXU and comparator after 6 months of therapy. Udgivelsesdato: 2007-Oct...

Retinol binding protein 4, obesity, and insulin resistance in adolescents

Directory of Open Access Journals (Sweden)

Ronaldi Noor

2017-02-01

Full Text Available Background Obesity is a global problem. Even in poor and developing countries, obesity has reached alarming levels. In childhood, obesity may lead to insulin resistance. Retinol binding protein (RBP4, secreted primarily by liver and adipose tissues, was recently proposed as a link between obesity and insulin resistance. The role of RBP4 in pediatric obesity and its relationship with insulin resistance have not been well elucidated. Objective To compare RBP4 levels in obese and lean adolescents and to assess for a relationship between RBP4 levels and insulin resistance. Method This cross-sectional study was conducted in three senior high schools in Padang, West Sumatera, Indonesia. Subjects were adolescents aged 14-18 years, who were obese or normal weight (n=56. We measured subjects’ body mass index (BMI and serum RBP4 concentrations. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR index. Results Similar RBP4 levels were found in the obese and normoweight groups (P>0.05. Higher RBP4 levels were found in the insulin resistant compared to the non-insulin resistant group, but the difference was not significant (P > 0.05. Conclusion There is no significant difference in mean RBP4 levels in obese adolescents compared to normoweight adolescents. Nor are mean RBP4 levels significantly different between obese adolescents with and without insulin resistance.

Insulin-like growth factors: assay methods and their implications

International Nuclear Information System (INIS)

Guyda, H.J.; Posner, B.I.; Schiffrin, A.; Rappaport, R.; Postel-Vinay, M.C.; Corvol, M.T.

1981-01-01

The insulin-like growth factors (IGF's) are small molecular weight peptides (6-10 x 10 3 daltons) that circulate in blood plasma almost entirely bound to macromolecular carrier proteins. The growth-promoting and insulin-like activities of IGF's can be explained by the observed ability of these peptides to interact with the IGF receptor on the one hand and with the insulin receptor on the other. These observations have led to the establishment of radioreceptor assays (RRA's), competitive protein binding assays (CPBA's), and more recently radioimmunoassays (RIA's) for the IGF's that have different specificities. Because of their ease of performance and sensitivity, the radioligand assays have largely supplanted the biological assays originally utilized to identify and characterize these anabolic peptides. In this report the authors' studies are summarised which utilize a slightly acidic IGF which has been purified on the basis of its insulin-like activity in an insulin RRA and which was termed ILAs. They refer to purified insulin-like peptides that have the properties of a somatomedin by the generic term insulin-like growth factor (IGF). Somatomedin (SM) activity will be utilized to connote that activity in plasma or serum determined by bioassay. The competitive dose-response curves for IGF peptides in the insulin RRA as well as those in the ILAs RRA are presented. A combination of bioassays, RRA and RIA were employed to assess somatomedin activity and IGF peptide levels in a number of clinical circumstances. The correlations are discussed. (Auth.)

New ways of insulin delivery.

Science.gov (United States)

Heinemann, L

2011-02-01

The predominant number of papers published from the middle of 2009 to the middle of 2010 about alternative routes of insulin administration (ARIA) were still about inhaled insulin. Long-term experience with Exubera was the topic of a number of publications that are also of relevance for inhaled insulin in general. The clinical trials performed with AIR insulin by Eli Lilly were published in a supplement issue of one diabetes technology journal and most of these will be presented. A number of other publications (also one in a high ranked journal) about their inhaled insulin were from another company: MannKind. The driving force behind Technosphere insulin (TI) - which is the only one still in clinical development - is Al Mann; he has put a lot of his personal fortune in this development. We will know the opinion of the regulatory authorities about TI in the near future; however, I am personally relatively confident that the Food and Drug Administration will provide TI with market approval. The more critical question for me is: will diabetologists and patients jump on this product once it becomes commercially available? Will it become a commercial success? In view of many negative feelings in the scientific community about inhaled insulin, it might be of help that MannKind publish their studies with TI systematically. Acknowledging being a believer in this route of insulin administration myself, one has to state that Exubera and AIR insulin had not offered profound advantages in terms of pharmacokinetic (PK) and pharmacodynamic (PD) properties in comparison with subcutaneously (SC) applied regular human insulin (RHI) and rapid-acting insulin analogues. The time-action profiles of these inhaled insulins were more or less comparable with that of rapid-acting insulin analogues. This is clearly different with TI which exhibits a strong metabolic effect shortly after application and a rapid decline in the metabolic effect thereafter; probably the duration of action is

Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

Science.gov (United States)

Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

2013-12-05

Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1β (10pg/ml) for 24h. IL-1β increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor β expression. Furthermore, IL-1β inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1β alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1β treatment. Moreover, IL-1β inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1β inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1β levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth. Published by Elsevier Ireland Ltd.

Novel simple insulin delivery device reduces barriers to insulin therapy in type 2 diabetes: results from a pilot study.

Science.gov (United States)

Hermanns, Norbert; Lilly, Leslie C; Mader, Julia K; Aberer, Felix; Ribitsch, Anja; Kojzar, Harald; Warner, Jay; Pieber, Thomas R

2015-05-01

The PaQ® insulin delivery system is a simple-to-use patch-on device that provides preset basal rates and bolus insulin on demand. In addition to feasibility of use, safety, and efficacy (reported elsewhere), this study analyzed the impact of PaQ on patient-reported outcomes, including barriers to insulin treatment, diabetes-related distress, and attitudes toward insulin therapy in patients with type 2 diabetes on a stable multiple daily injection (MDI) regimen. This single-center, open-label, single-arm study comprised three 2-week periods: baseline (MDI), transition from MDI to PaQ, and PaQ treatment. Validated questionnaires were administered during the baseline and PaQ treatment periods: Barriers to Insulin Treatment questionnaire (BIT), Insulin Treatment Appraisal Scale (ITAS), and Problem Areas in Diabetes scale (PAID). Eighteen patients (age 59 ± 5 years, diabetes duration 15 ± 7 years, 21% female, HbA1c 7.7 ± 0.7%) completed the questionnaires. There was a strong, significant effect of PaQ use in mean BIT total scores (difference [D] = -5.4 ± 0.7.7, P = .01, effect size [d] = 0.70). Patients perceived less stigmatization by insulin injection (D = -2.2 ± 6.2, P = .18, d = 0.35), increased positive outcome (D = 1.9 ± 6.6, P = .17, d = 0.29), and less fear of injections (1.3 ± 4.8, P = .55, d = 0.28). Mean change in ITAS scores after PaQ device use showed a nonsignificant improvement of 1.71 ± 5.63 but moderate effect size (d = 0.30, P = .14). No increase in PAID scores was seen. The results and moderate to large effects sizes suggest that PaQ device use has beneficial and clinically relevant effects to overcoming barriers to and negative appraisal of insulin treatment, without increasing other diabetes-related distress. © 2015 Diabetes Technology Society.

Pancreas-After-Islet Transplantation in Nonuremic Type 1 Diabetes: A Strategy for Restoring Durable Insulin Independence.

Science.gov (United States)

Wisel, S A; Gardner, J M; Roll, G R; Harbell, J; Freise, C E; Feng, S; Kang, S M; Hirose, R; Kaufman, D B; Posselt, A M; Stock, P G

2017-09-01

Islet transplantation offers a minimally invasive approach for β cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet reinfusions from distinct donors, increasing the risk of allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the United States; however, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear. We describe a case series of seven patients undergoing solid organ pancreas transplant following islet graft failure with long-term follow-up of pancreatic graft survival and renal function. Despite highly variable panel reactive antibody levels prior to pancreas transplant (mean 27 ± 35%), all seven patients achieved stable and durable insulin independence with a mean follow-up of 6.7 years. Mean hemoglobin A1c values improved significantly from postislet, prepancreas levels (mean 8.1 ± 1.5%) to postpancreas levels (mean 5.3 ± 0.1%; p = 0.0022). Three patients experienced acute rejection episodes that were successfully managed with thymoglobulin and methylprednisolone, and none of these preuremic type 1 diabetic recipients developed stage 4 or 5 chronic kidney disease postoperatively. These results support pancreas-after-islet transplantation with aggressive immunosuppression and protocol biopsies as a viable strategy to restore insulin independence after islet graft failure. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Existential Meaning Among First-Time Full-Term and Preterm Mothers

DEFF Research Database (Denmark)

Prinds, Christina; Hvidtjørn, Dorte; Mogensen, Ole

2014-01-01

Research indicates that childbirth is a time when a woman might experience existential disruptions and gain new perspectives on life. The 2-fold aim of this study was to investigate whether attitudes related to existential meaning among first-time mothers intensify and whether they differ between...... mothers who gave birth at full term and those who gave birth preterm. All first-time mothers who gave birth in Denmark in 2010 before the 32nd week of pregnancy and twice that number of full-term mothers (randomly sampled) were invited to participate in a national cross-sectional survey. Five core items...... concerning meaning in life, vulnerability of life, responsibility, thoughts about life and death, and "something bigger than oneself" were analyzed to compare mothers' attitudes on existential meaning. The overall response rate was 57% (517/913). Contrary to the hypothesis, attitudes related to existential...

Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy

DEFF Research Database (Denmark)

Olsen, Michael H; Fossum, Eigil; Høieggen, Aud

2005-01-01

Hypertension and insulin resistance might be associated through peripheral vascular hypertrophy/rarefaction which compromises skeletal muscle blood flow and decreases glucose uptake, inducing insulin resistance. We hypothesized that treatment with losartan as compared to atenolol would improve...... insulin sensitivity through regression of peripheral vascular hypertrophy/rarefaction....

Absorption of subcutaneously infused insulin: influence of the basal rate pulse interval.

Science.gov (United States)

Hildebrandt, P; Birch, K; Jensen, B M; Kühl, C; Brange, J

1985-01-01

Eight insulin-dependent diabetic patients were given two constant infusions (each 1 IU/h) of 125I-labeled insulin into the abdominal subcutaneous tissue for about 12 h. Insulin was infused in pulses into one side of the abdomen in 6-min intervals (by means of an Auto-Syringe pump) and in the other side of the abdomen, insulin was infused in 1-h intervals (by means of a Medix pump). The size of the subcutaneous depots was continuously measured by counting the radioactivity at the infusion sites. After starting the infusions, the two depots were built up to steady-state levels at the same time and of the same size (approximately 3 IU) and with similar absorption rates. Thus, during basal rate insulin infusion, identical insulin absorption kinetics was achieved, irrespective of a 10-fold difference in the pulse rate.

Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

Science.gov (United States)

Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

2011-01-01

The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696

Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

International Nuclear Information System (INIS)

Naidoo, C.

1986-01-01

Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, 125 I-insulin binding to the solubilized erythrocyte membrane receptor and 125 I-insulin binding to fibroblasts in culture

Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

Energy Technology Data Exchange (ETDEWEB)

Naidoo, C

1986-01-01

Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, /sup 125/I-insulin binding to the solubilized erythrocyte membrane receptor and /sup 125/I-insulin binding to fibroblasts in culture.

Negative appraisals of insulin therapy are common among adults with Type 2 diabetes using insulin: Results from Diabetes MILES - Australia cross-sectional survey

DEFF Research Database (Denmark)

Holmes-Truscott, E.; Holmes-Truscott, E.; Skinner, T. C.

2015-01-01

Aim: To identify insulin therapy appraisals among adults with Type 2 diabetes using insulin and how negative appraisals relate to clinical, self-care and psychosocial outcomes. Methods: Diabetes MILES - Australia 2011 was a national survey of adults with diabetes, focused on behavioural...... and psychosocial issues. Subgroup analyses were conducted on the responses of 273 adults with Type 2 diabetes using insulin (46% women; mean ± sd age: 59 ± 9 years; diabetes duration: 12 ± 7 years; years using insulin: 4 ± 4). They completed validated measures of insulin therapy appraisals (ITAS), depression (PHQ......; 51% that insulin causes weight gain; 39% that they have 'failed to manage' their diabetes. Those with the greatest and least 'ITAS negative' scores did not differ by diabetes duration or years using insulin, or by average number of insulin injections or blood glucose checks per day. Those with more...

Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome

DEFF Research Database (Denmark)

Buhl, Esben Selmer; Jessen, Niels; Pold, Rasmus

2002-01-01

, upregulate mitochondrial enzymes in skeletal muscles, and decrease the content of intra-abdominal fat. Furthermore, acute AICAR exposure has been found to reduce sterol and fatty acid synthesis in rat hepatocytes incubated in vitro as well as suppress endogenous glucose production in rats under euglycemic......-treated animals exhibited a tendency toward decreased intra-abdominal fat content. Furthermore, AICAR administration normalized the oral glucose tolerance test and decreased fasting concentrations of glucose and insulin close to the level of the lean animals. Finally, in line with previous findings, AICAR...... treatment was also found to enhance GLUT4 protein expression and to increase maximally insulin-stimulated glucose transport in primarily white fast-twitch muscles. Our data provide strong evidence that long-term administration of AICAR improves glucose tolerance, improves the lipid profile, and reduces...

The early use of insulin in type 2 diabetes

Directory of Open Access Journals (Sweden)

PHILIP LEVY

2004-06-01

Full Text Available 60?70% of all patients with Type 2 Diabetes Mellitus will ultimately require insulin therapy for the management of their diabetes. Irisulin may be used alone, or in combination with oral agents. The early use of insulin can be very important in decreasing the incidence of micro-vascular complications and in helping to delay the onset of macro-vascular complications. The United Kingdom Prospective Diabetes Study and the Kumamoto Study have shown the beneficial effects of good glucose control in type 2 diabetes mellitus. The DECODE study has related overall mortality to the level of glucose control and specifically to the postprandial glucose. The American Association of Clinical Endocrinologists has established a goal of 6.5% or less for HgbAlc. The appropriate use of insulin will allow us to achieve this goal without causing the patient any undue harm. There are many barriers to insulin therapy including psychological barriers of both the patient and the doctor, and unrealistic fears of both insulin therapy and therapy with self-administered injections. These barriers will be discussed as well as methods to overcome them. Insulin therapy is beneficial and has no long term adverse effects. The incidence of severe hypoglycemia is extremely low in type 2 diabetes. Weight gain is minimal. Insulin therapy by reducing glucose toxicity may also increase the effectiveness of oral anti-hyperglycemic agents. The physician taking care of patients with diabetes should be aggressive and should have no fears of initiating insulin therapy. Insulin dosage is flexible and good control is possible in most patients. The most common use of insulin in type 2 diabetes is as an add-on to oral agents if control with oral agents alone is unsatisfactory. Frequently this involves the use of a single dose of intermediate or long acting insulin or an insulin mixture in the evening. If control is not attained with a single dose, then the patient can be placed on an insulin

Trajectories of BMI change impact glucose and insulin metabolism.

Science.gov (United States)

Walsh, E I; Shaw, J; Cherbuin, N

2018-03-01

The aim of this study was to examine, in a community setting, whether trajectory of weight change over twelve years is associated with glucose and insulin metabolism at twelve years. Participants were 532 community-living middle-aged and elderly adults from the Personality and Total Health (PATH) Through Life study. They spanned the full weight range (underweight/normal/overweight/obese). Latent class analysis and multivariate generalised linear models were used to investigate the association of Body Mass Index (BMI, kg/m 2 ) trajectory over twelve years with plasma insulin (μlU/ml), plasma glucose (mmol/L), and HOMA2 insulin resistance and beta cell function at follow-up. All models were adjusted for age, gender, hypertension, pre-clinical diabetes status (normal fasting glucose or impaired fasting glucose) and physical activity. Four weight trajectories were extracted; constant normal (mean baseline BMI = 25; follow-up BMI = 25), constant high (mean baseline BMI = 36; follow-up BMI = 37), increase (mean baseline BMI = 26; follow-up BMI = 32) and decrease (mean baseline BMI = 34; follow-up BMI = 28). At any given current BMI, individuals in the constant high and increase trajectories had significantly higher plasma insulin, greater insulin resistance, and higher beta cell function than those in the constant normal trajectory. Individuals in the decrease trajectory did not differ from the constant normal trajectory. Current BMI significantly interacted with preceding BMI trajectory in its association with plasma insulin, insulin resistance, and beta cell function. The trajectory of preceding weight has an independent effect on blood glucose metabolism beyond body weight measured at any given point in time. Copyright © 2017 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

Original meaning of the notion and term “formation” in geology

Directory of Open Access Journals (Sweden)

Grubić Aleksandar

2014-01-01

Full Text Available The notion of (geological formation has gradually developed through mostly German terms: from ein Gebirge, which was used by Saxon miners for several centuries (AGRICOLA, then Schichten, Bergart (LEHMANN and serie montana (FUCHSEL to Gebirgsart (WERNER. The term ‘formation’ was introduced by WERNER in 1791 and its meaning was clearly defined around 1800. He included the notion of “formation” into his system of “geognostic structures”: mineral; rock (layer; formation; Earth’s crust. Therefore, it was an equivocal term from the start. It implied a geological body of certain composition, genesis and superposition (i.e. time of origination. After Werner, the term ‘formation’ was used in different ways, mostly as a synonym for a ‘system’, until 1881 when such use was forbidden. The original Wernerian sense of the term ‘formation’ (as a unit in geological levels of organisation: mineral-rock-formation-geosphere-planet with an intentionally equivocal meaning was not restored until the second half of the twentieth century.

Association between insulin resistance and c-reactive protein among Peruvian adults

Directory of Open Access Journals (Sweden)

Gelaye Bizu

2010-05-01

Full Text Available Abstract Objective Insulin resistance (IR, a reduced physiological response of peripheral tissues to the action of insulin, is one of the major causes of type 2 diabetes. We sought to evaluate the relationship between serum C-reactive protein (CRP, a marker of systemic inflammation, and prevalence of IR among Peruvian adults. Methods This population based study of 1,525 individuals (569 men and 956 women; mean age 39 years old was conducted among residents in Lima and Callao, Peru. Fasting plasma glucose, insulin, and CRP concentrations were measured using standard approaches. Insulin resistance was assessed using the homeostasis model (HOMA-IR. Categories of CRP were defined by the following tertiles: 2.53 mg/l. Logistic regression procedures were employed to estimate odds ratios (OR and 95% confidence intervals (CI. Results Elevated CRP were significantly associated with increased mean fasting insulin and mean HOMA-IR concentrations (p 2.53 mg/l (upper tertile had a 2.18-fold increased risk of IR (OR = 2.18 95% CI 1.51-3.16 as compared with those in the lowest tertile ( Conclusion Our observations among Peruvians suggest that chronic systemic inflammation, as evidenced by elevated CRP, may be of etiologic importance in insulin resistance and diabetes.

Degludec insulin: A novel basal insulin

OpenAIRE

Kalra, Sanjay; Unnikrishnan, Ambika Gopalakrishnan; Baruah, Manash; Kalra, Bharti

2011-01-01

This paper reviews a novel insulin analogue, degludec, which has the potential to emerge as an ideal basal insulin. It reviews the limitations of existing basal insulin and analogues, and highlights the need for a newer molecule. The paper discusses the potential advantages of degludec, while reviewing its pharmacologic and clinical studies done so far. The paper assesses the potential role of insulin degludec and degludec plus in clinical diabetes practice.

Birth-weight, insulin levels, and HOMA-IR in newborns at term.

Science.gov (United States)

Simental-Mendía, Luis E; Castañeda-Chacón, Argelia; Rodríguez-Morán, Martha; Guerrero-Romero, Fernando

2012-07-07

Recent studies have demonstrated that low and high birth-weight at birth are risk factors of developing diabetes. The aim of this study was to determine if the abnormal birth-weight is related with hyperinsulinemia and elevated index of the Homeostasis Model assessment for Insulin Resistance (HOMA-IR) at birth, in at term newborns. Newborns with gestational age between 38 and 41 weeks, products of normal pregnancies of healthy mothers aged 18 to 39 years, were eligible to participate. Small-for-gestational age (SGA) and large-for-gestational age (LGA) newborns were compared with appropriate-for-gestational (AGA) age newborns. Incomplete or unclear data about mother's health status, diabetes, gestational diabetes, history of gestational diabetes, hypertension, pre-eclampsia, eclampsia, and other conditions that affect glucose metabolism were exclusion criteria. Hyperinsulinemia was defined by serum insulin levels ≥13.0 μU/mL and IR by HOMA-IR ≥2.60. Multiple logistic regression analysis was used to determine the odds ratio (OR) that computes the association between birth-weight (independent variable) with hyperinsulinemia and HOMA-IR index (dependent variables). A total of 107 newborns were enrolled; 13, 22, and 72 with SGA, LGA, and AGA, respectively. Hyperinsulinemia was identified in 2 (15.4%), 6 (27.3%), and 5 (6.9%) with SGA, LGA, and AGA (p=0.03), whereas IR in 3 (23.1%), 8 (36.4%), and 10 (13.9%) newborns with SGA, LGA and AGA (p=0.06). The LGA showed a strong association with hyperinsulinemia (OR 5.02; CI 95%, 1.15-22.3; p=0.01) and HOMA-IR (OR 3.54; CI 95%, 1.03-12.16; p=0.02); although without statistical significance, the SGA showed a tendency of association with hyperinsulinemia (OR 2.43; CI 95%, 0.43-17.3 p=0.29) and HOMA-IR (OR 1.86; CI 95%, 0.33-9.37; p=0.41). Our results suggest that LGA is associated with hyperinsulinemia and elevated HOMA-IR at birth whereas the SGA show a tendency of association.

Insulin resistance induced by hydrocortisone is increased in patients with abdominal obesity.

Science.gov (United States)

Darmon, Patrice; Dadoun, Frédéric; Boullu-Ciocca, Sandrine; Grino, Michel; Alessi, Marie-Christine; Dutour, Anne

2006-11-01

Glucocorticoids hypersensitivity may be involved in the development of abdominal obesity and insulin resistance. Eight normal weight and eight obese women received on two occasions a 3-h intravenous infusion of saline or hydrocortisone (HC) (1.5 microg x kg(-1) x min(-1)). Plasma cortisol, insulin, and glucose levels were measured every 30 min from time(-30) (min) (time(-30)) to time(240). Free fatty acids, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were measured at time(-30), time(180), and time(240). At time(240), subjects underwent an insulin tolerance test to obtain an index of insulin sensitivity (K(ITT)). Mean(30-240) cortisol level was similar in control and obese women after saline (74 +/- 16 vs. 75 +/- 20 microg/l) and HC (235 +/- 17 vs. 245 +/- 47 microg/l). The effect of HC on mean(180-240) insulin, mean(180-240) insulin resistance obtained by homeostasis model assessment (HOMA-IR), and K(ITT) was significant in obese (11.4 +/- 2.0 vs. 8.2 +/- 1.3 mU/l, P obese women (+25%) than in controls (+12%) (P obese women than in controls. These deleterious effects are correlated with the amount of visceral fat.

Identifying Meaning Components in the Translation of Medical Terms from English into Indonesian: A Semantic Approach

Directory of Open Access Journals (Sweden)

I Gusti Agung Sri Rwa Jayantini

2017-10-01

Full Text Available This paper focuses on identifying meaning components in the translation of English medical terms into Indonesian. The data used in this study are the English medical term disorder and its Indonesian equivalent penyakit (disease. The two terms are purposively chosen as the data of the present study, which is a comparative research on the lexical meaning investigation in two different languages. The investigation involving a particular term in one language and its equivalent in the other language is worth doing since the lexicons in every language have their own specific concepts that may be synonymous, yet they are not always interchangeable in all contexts. The analysis into meaning components is called decomposition by means of several semantic theories to analyse the meaning of a lexical item (Löbner 2013. Here, the meaning components of the two compared terms are demonstrated through a semantic approach, particularly Natural Semantic Metalanguage (NSM supported by the investigation on their synonyms and how the terms are used in different contexts. The results show that the meaning components of a particular term in one language like the English term disorder are not always found in the Indonesian term penyakit, or, conversely, some of the meaning components of the Indonesian term do not always exist in the English term.

Insulin-like growth factor 1, liver enzymes, and insulin resistance in patients with PCOS and hirsutism.

Science.gov (United States)

Çakir, Evrim; Topaloğlu, Oya; Çolak Bozkurt, Nujen; Karbek Bayraktar, Başak; Güngüneş, Aşkın; Sayki Arslan, Müyesser; Öztürk Ünsal, İlknur; Tutal, Esra; Uçan, Bekir; Delıbaşi, Tuncay

2014-01-01

Hyperinsulinemia and insulin resistance are commonly seen in patients with hirsutism and polycystic ovary syndrome (PCOS), and are associated with cardiovascular disease risk. However, it is not yet known whether insulin-like growth factor I (IGF-I) and alanine transaminase (ALT) produced by the liver play roles in hyperinsulinemia and subclinical atherosclerotic process in patients with PCOS and idiopathic hirsutism (IH). This was a prospective case-controlled study. The study population consisted of 25 reproductive-age PCOS women, 33 women with IH, and 25 control subjects. Mean IGF-I levels and median ALT levels were higher in patients with IH and PCOS than controls, but these differences were not statistically significant. The participants who had a homeostasis model assessment insulin resistance index (HOMA-IR) greater than 2.7 had significantly higher IGF-1 and ALT levels. ALT levels were positively correlated with body mass index, FG, insulin and HOMA-IR. The study illustrated that IGF-1 and ALT levels were significantly higher in patients with increased insulin resistance. Due to short disease duration in younger participants, we did not observe any correlation between IGF-1 and hyperinsulinemia. These findings suggest that increased hepatic production of IGF-I and ALT might be an early indicator of insulin resistance in hirsutism.

Insulin resistance in obese children and adolescents.

Science.gov (United States)

Romualdo, Monica Cristina dos Santos; Nóbrega, Fernando José de; Escrivão, Maria Arlete Meil Schimith

2014-01-01

To evaluate the presence of insulin resistance and its association with other metabolic abnormalities in obese children and adolescents. Retrospective study of 220 children and adolescents aged 5-14 years. Anthropometric measurements were performed (weight, height, and waist circumference) and clinical (gender, age, pubertal stage, and degree of obesity) and biochemical (glucose, insulin, total cholesterol, and fractions, triglycerides) data were analyzed. Insulin resistance was identified by the homeostasis model assessment for insulin resistance (HOMA-IR) index. The analysis of the differences between the variables of interest and the HOMA-IR quartiles was performed by ANOVA or Kruskal-Wallis tests. Insulin resistance was diagnosed in 33.20% of the sample. It was associated with low levels of high-density lipoprotein cholesterol (HDL-C; p=0.044), waist circumference measurement (p=0.030), and the set of clinical and metabolic (p=0.000) alterations. Insulin-resistant individuals had higher mean age (p=0.000), body mass index (BMI; p=0.000), abdominal circumference (p=0.000), median triglycerides (p=0.001), total cholesterol (p≤0.042), and low-density lipoprotein cholesterol (LDL-C; p≤0.027); and lower HDL-C levels (p=0.005). There was an increase in mean BMI (p=0.000), abdominal circumference (p=0.000), and median triglycerides (p=0.002) as the values of HOMA -IR increased, with the exception of HDL-C, which decreased (p=0.001). Those with the highest number of simultaneous alterations were between the second and third quartiles of the HOMA-IR index (p=0.000). The results confirmed that insulin resistance is present in many obese children and adolescents, and that this condition is associated with alterations that represent an increased risk for developing metabolic disorders in adulthood. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Blueberries’ Impact on Insulin Resistance and Glucose Intolerance

Directory of Open Access Journals (Sweden)

April J. Stull

2016-11-01

Full Text Available Blueberries are a rich source of polyphenols, which include anthocyanin bioactive compounds. Epidemiological evidence indicates that incorporating blueberries into the diet may lower the risk of developing type 2 diabetes (T2DM. These findings are supported by pre-clinical and clinical studies that have shown improvements in insulin resistance (i.e., increased insulin sensitivity after obese and insulin-resistant rodents or humans consumed blueberries. Insulin resistance was assessed by homeostatic model assessment-estimated insulin resistance (HOMA-IR, insulin tolerance tests, and hyperinsulinemic-euglycemic clamps. Additionally, the improvements in glucose tolerance after blueberry consumption were assessed by glucose tolerance tests. However, firm conclusions regarding the anti-diabetic effect of blueberries cannot be drawn due to the small number of existing clinical studies. Although the current evidence is promising, more long-term, randomized, and placebo-controlled trials are needed to establish the role of blueberries in preventing or delaying T2DM.

Insulin use and persistence in patients with type 2 diabetes adding mealtime insulin to a basal regimen: a retrospective database analysis

Directory of Open Access Journals (Sweden)

Torres Amelito M

2011-01-01

Full Text Available Abstract Background The objective of this study was to characterize insulin use and examine factors associated with persistence to mealtime insulin among patients with type 2 diabetes (T2D on stable basal insulin therapy initiating mealtime insulin therapy. Methods Insulin use among patients with T2D initiating mealtime insulin was investigated using Thomson Reuters MarketScan® research databases from July 2001 through September 2006. The first mealtime insulin claim preceded by 6 months with 2 claims for basal insulin was used as the index event. A total of 21 months of continuous health plan enrollment was required. Patients were required to have a second mealtime insulin claim during the 12-month follow-up period. Persistence measure 1 defined non-persistence as the presence of a 90-day gap in mealtime insulin claims, effective the date of the last claim prior to the gap. Persistence measure 2 required 1 claim per quarter to be persistent. Risk factors for non-persistence were assessed using logistic regression. Results Patients initiating mealtime insulin (n = 4752; 51% male, mean age = 60.3 years primarily used vial/syringe (87% and insulin analogs (60%. Patients filled a median of 2, 3, and 4 mealtime insulin claims at 3, 6, and 12 months, respectively, with a median time of 76 days between refills. According to measure 1, persistence to mealtime insulin was 40.7%, 30.2%, and 19.1% at 3, 6, and 12 months, respectively. Results for measure 2 were considerably higher: 74.3%, 55.3%, and 42.2% of patients were persistent at 3, 6, and 12 months, respectively. Initiating mealtime insulin with human insulin was a risk factor for non-persistence by both measures (OR Conclusions Mealtime insulin use and persistence were both considerably lower than expected, and were significantly lower for human insulin compared to analogs.

Insulin secretion and insulin action in non-insulin-dependent diabetes mellitus: which defect is primary?

Science.gov (United States)

Reaven, G M

1984-01-01

Defects in both insulin secretion and insulin action exist in patients with non-insulin-dependent diabetes mellitus (NIDDM). The loss of the acute plasma insulin response to intravenous glucose is seen in patients with relatively mild degrees of fasting hyperglycemia, but patients with severe fasting hyperglycemia also demonstrate absolute hypoinsulinemia in response to an oral glucose challenge. In contrast, day-long circulating insulin levels are within normal limits even in severely hyperglycemic patients with NIDDM. The relationship between NIDDM and insulin action in NIDDM is less complex, and is a characteristic feature of the syndrome. This metabolic defect is independent of obesity, and the severity of the resistance to insulin-stimulated glucose uptake increases with magnitude of hyperglycemia. Control of hyperglycemia with exogenous insulin ameliorates the degree of insulin resistance, and reduction of insulin resistance with weight loss in obese patients with NIDDM leads to an enhanced insulin response. Since neither therapeutic intervention is capable of restoring all metabolic abnormalities to normal, these observations do not tell us which of these two defects is primarily responsible for the development of NIDDM. Similarly, the observation that most patients with impaired glucose tolerance are hyperinsulinemic and insulin resistant does not prove that insulin resistance is the primary defect in NIDDM. In conclusion, reduction in both insulin secretion and action is seen in patients with NIDDM, and the relationship between these two metabolic abnormalities is very complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose and insulin dynamics associated with continuous rate infusion of dextrose solution or dextrose solution and insulin in healthy and endotoxin-exposed horses.

Science.gov (United States)

Han, Janet H; McKenzie, Harold C; McCutcheon, L Jill; Geor, Raymond J

2011-04-01

To investigate the effects of a continuous rate infusion (CRI) of dextrose solution or dextrose solution and insulin on glucose and insulin concentrations in healthy and endotoxin-exposed horses. 9 adult mares. During phase 1, treatments consisted of saline (0.9% NaCl) solution (control group; n = 4) or 20% dextrose solution (group 1; 4) administered IV as a 360-minute CRI. During phase 2, treatments consisted of 360-minute CRIs of 20% dextrose solution and insulin administered simultaneously at 367.6 mg/kg/h (30 kcal/kg/d) and 0.07 U/kg/h, respectively, in healthy horses (group 2; n = 4) or horses administered 35 ng of lipopolysaccharide/kg, IV, 24 hours before starting the dextrose solution and insulin CRIs (group 3; 4). A balanced crossover study design was used in both phases. Blood samples were collected for measurement of plasma glucose and insulin concentrations. Infusion of dextrose solution alone resulted in hyperglycemia for most of the 360-minute CRI. Insulin concentration increased significantly in group 1, compared with that in the control group. Mean insulin concentration of group 2 was significantly higher throughout most of the infusion period, compared with concentrations of the control group and group 1. Mean glucose concentration did not differ significantly between groups 2 and 3. Insulin infusion at a rate of 0.07 U/kg/h was found to be effective for the prevention of hyperglycemia when administered concurrently with dextrose solution. This rate was considered to be safe because horses did not become hypoglycemic during infusions of dextrose solution.

Correlation between the Plasma Insulin and Glucose Concentration in Normal Korean Adults

Energy Technology Data Exchange (ETDEWEB)

Lee, Jang Kyu; Sung, Ho Kyung; Kim, Jin Eui [Radiological Research Institute, Seoul (Korea, Republic of)

1971-09-15

The correlation between the plasma insulin, and glucose concentration was studied in healthy Korean adults consisting of 20 males and 22 females of 16 to 38 years of age. The blood samples of above subjects were obtained through cubital vein at arbitrary times during their usual working hours. Plasma insulin was assayed by means of double antibody system of radioimmunoassay technics, and blood glucose was determined by means of Van Slyke-Folch method. Results were as follows : 1. There were no differences in the blood sugar levels in relation to the plasma insulin concentration either by sex or age. 2. In the case, when the plasma insulin concentration was within 50 mmuU/ml, the correlation between the insulin, and glucose concentration existed, the ratio of which was expressed as; Plasma glucose concentration (mg/dl)=91.9 + 0.08 X Insulin concentration r=0.62. 3. Insulinogenic index was 12.4%, which was somewhat higher than other reports. 4. It is suggested that the correlation between plasma insulin and glucose concentration could be determined at arbitrary times instead of fasting times.

Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity.

Science.gov (United States)

Kim, Young-Je; Choi, Myung-Sook; Woo, Je Tae; Jeong, Mi Ji; Kim, Sang Ryong; Jung, Un Ju

2017-08-01

We evaluated the long-term effect of low-dose nobiletin (NOB), a polymethoxylated flavone, on diet-induced obesity and related metabolic disturbances. C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without NOB (0.02%, w/w) for 16 weeks. NOB did not alter food intake or body weight. Despite increases in fatty acid oxidation-related genes expression and enzymes activity in adipose tissue, NOB did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity. However, NOB significantly decreased not only pro-inflammatory genes expression in adipose tissue but also proinflammatory cytokine levels in plasma. NOB-supplemented mice also showed improved glucose tolerance and insulin resistance, along with decreased levels of plasma insulin, free fatty acids, total cholesterol, non-HDL-cholesterol, and apolipoprotein B. In addition, NOB caused significant decreases in hepatic lipid droplet accumulation and triglyceride content by activating hepatic fatty acid oxidation-related enzymes. Hepatic proinflammatory TNF-α mRNA expression, collagen accumulation, and plasma levels of aminotransferases, liver damage indicators, were also significantly lower in NOB-supplemented mice. These findings suggest that long-term supplementation with low-dose NOB can protect against HFD-induced inflammation, insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease, without ameliorating adiposity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes

DEFF Research Database (Denmark)

Zinman, Bernard; Philis-Tsimikas, Athena; Cariou, Bertrand

2012-01-01

To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).......To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs)....

Glucose but not insulin or insulin resistance is associated with memory performance in middle-aged non-diabetic women : a cross sectional study

OpenAIRE

Backeström, Anna; Eriksson, Sture; Nilsson, Lars-Göran; Olsson, Tommy; Rolandsson, Olov

2015-01-01

Background: Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population.  Methods: We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 +/- 8.0...

Current understanding of increased insulin sensitivity after exercise - emerging candidates

DEFF Research Database (Denmark)

Maarbjerg, Stine Just; Sylow, Lykke; Richter, Erik

2011-01-01

signaling component in the insulin signaling pathway such as aPKC, Rac1, TBC1D4 and TBC1D1 have been described. These are all affected by both insulin and exercise which means that they are likely converging points in promoting GLUT4 translocation and therefore possible candidates for regulating insulin...... sensitivity after exercise. Whereas TBC1D1 does not appear to regulate insulin sensitivity after exercise, correlative evidence in contrast suggests TBC1D4 to be a relevant candidate. Little is known about aPKC and Rac1 in relation to insulin sensitivity after exercise. Besides mechanisms involved...

Selection of well labelled insulin fractions for radioimmunoassay use

Energy Technology Data Exchange (ETDEWEB)

Awh, O D; Kim, J R [Korea Atomic Energy Research Inst., Seoul (Republic of Korea)

1980-06-01

Selection methods of well labelled insulin fractions based on two different criteria were compared to establish an efficient low level RIA of insulin and to elucidate the correlation between the immunoreactivity and the charcoal-adsorptivity of the radioiodine labelled insulin. The result indicated that the selection of well labelled insulin fractions by means of a charcoal-adsorption test is inappropriate. Generally, the distribution of radioactivity, antibody-bindability, and charcoal-adsorptivity of the labelled insulin was not consistent with each other. Thus, the selection should be carried out for every labelling batch to get the utmost assay reliability by antibody-bindability but not by charcoal-adsorptivity. By using the well selected labelled insulin fractions based on antibody-binding, a correct assay for a reference serum was possible, and by extending the incubation time up to 96 hrs, a sharp dose response curve could be obtained even in the range of below 5 ..mu..U/ml standard insulin doses.

Expression of insulin receptor spliced variants and their functional correlates in muscle from patients with non-insulin-dependent diabetes mellitus

DEFF Research Database (Denmark)

Hansen, Torben; Bjørbaek, C; Vestergaard, H

1993-01-01

Due to alternative splicing of exon 11 of the receptor gene, the human insulin receptor exists in two forms, that have distinct tissue-specific expression and are functionally different. Needle biopsies obtained from vastus lateralis muscle from 20 patients with noninsulin-dependent diabetes...... kinase activity were examined in wheat germ agglutinin-purified insulin receptors isolated from muscle biopsies. Moreover, insulin-stimulated glucose disposal was studied by means of the euglycemic hyperinsulinemic clamp technique. No difference in the relative expression of spliced variants......, and tyrosine kinase activity toward the exogenous substrate poly(Glu-Tyr(4:1)). Furthermore, no significant relationship was demonstrated between the glucose disposal rate and the relative expression of insulin receptor splice variants. In conclusion, in skeletal muscle from both normal control subjects...

The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

OpenAIRE

Messier, Claude; Teutenberg, Kevin

2005-01-01

Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in a...

Semiclassical approximations in a mean-field theory with collision terms

International Nuclear Information System (INIS)

Galetti, D.

1986-01-01

Semiclassical approximations in a mean-field theory with collision terms are discussed taking the time dependent Hartree-Fock method as framework in the obtainment of the relevant parameters.(L.C.) [pt

2 CFR 182.105 - Do terms in this part have special meanings?

Science.gov (United States)

2010-01-01

... FOR GRANTS AND AGREEMENTS Reserved GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Purpose and Coverage § 182.105 Do terms in this part have special meanings? This part uses terms...

Function of insulin in snail brain in associative learning.

Science.gov (United States)

Kojima, S; Sunada, H; Mita, K; Sakakibara, M; Lukowiak, K; Ito, E

2015-10-01

Insulin is well known as a hormone regulating glucose homeostasis across phyla. Although there are insulin-independent mechanisms for glucose uptake in the mammalian brain, which had contributed to a perception of the brain as an insulin-insensitive organ for decades, the finding of insulin and its receptors in the brain revolutionized the concept of insulin signaling in the brain. However, insulin's role in brain functions, such as cognition, attention, and memory, remains unknown. Studies using invertebrates with their open blood-vascular system have the promise of promoting a better understanding of the role played by insulin in mediating/modulating cognitive functions. In this review, the relationship between insulin and its impact on long-term memory (LTM) is discussed particularly in snails. The pond snail Lymnaea stagnalis has the ability to undergo conditioned taste aversion (CTA), that is, it associatively learns and forms LTM not to respond with a feeding response to a food that normally elicits a robust feeding response. We show that molluscan insulin-related peptides are up-regulated in snails exhibiting CTA-LTM and play a key role in the causal neural basis of CTA-LTM. We also survey the relevant literature of the roles played by insulin in learning and memory in other phyla.

Effect of Insulin Infusion on insulin-like growth factor I (IGF-I) during Hemodialysis

DEFF Research Database (Denmark)

Reinhard, Mark; Frystyk, Jan; Bjerre, Mette

2012-01-01

Background: Hemodialysis (HD) is a catabolic procedure probably contributing to the high frequency of protein-energy wasting among patients on maintenance HD. The aim was to investigate the effect of insulin infusion on insulin-like growth factor I (IGF-I) during HD compared with a meal alone...... infusion and followed by the only meal allowed during the study. Results: Data are presented as mean±SD. From baseline to end of HD session we observed an overall increase in both serum bioactive IGF-I (from 0.83±0.27 to 1.01±0.34 µg/L, p... in the change between the groups (p=0.43). Conclusion: A meal at the beginning of a HD session leads to an increase in bioactive IGF-I thereby assumingly counteracting the catabolic effects of HD. However, according to changes in bioactive IGF-I neither glucose nor glucose-insulin infusion during HD appear...

Chitosan/lecithin liposomal nanovesicles as an oral insulin delivery system.

Science.gov (United States)

Al-Remawi, Mayyas; Elsayed, Amani; Maghrabi, Ibrahim; Hamaidi, Mohammad; Jaber, Nisrein

2017-05-01

In the present work, insulin-chitosan polyelectrolyte complexes associated to lecithin liposomes were investigated as a new carrier for oral delivery of insulin. The preparation was characterized in terms of particle size, zeta potential and encapsulation efficiency. Surface tension measurements revealed that insulin-chitosan polyelectrolyte complexes have some degree of hydrophobicity and should be added to lecithin liposomal dispersion and not the vice versa to prevent their adsorption on the surface. Stability of insulin was enhanced when it was associated to liposomes. Significant reduction of blood glucose levels was noticed after oral administration of liposomal preparation to streptozotocin diabetic rats compared to control. The hypoglycemic activity was more prolonged compared to subcutaneously administered insulin.

Omentin, an adipokine with insulin-sensitizing properties, is negatively associated with insulin resistance in normal gestation.

Science.gov (United States)

Brandt, Benny; Mazaki-Tovi, Shali; Hemi, Rina; Yinon, Yoav; Schiff, Eyal; Mashiach, Roy; Kanety, Hannah; Sivan, Eyal

2015-05-01

Omentin, a newly identified adipokine, enhances insulin mediated glucose uptake in human adipocytes, thus, inducing systemic insulin-sensitizing effect. The aims of this study were to determine whether circulating maternal omentin levels are associated with insulin resistance indices and to assess which compartment, maternal, fetal, or placental, is the source of omentin in maternal circulation. Fasting serum glucose, insulin, and omentin were determined in 25 healthy pregnant women at the third trimester, before and 3 days after elective cesarean section. Cord blood omentin was measured in the 25 term neonates. Homeostasis model assessment (HOMA) was used to evaluate insulin sensitivity before and after delivery. Antepartum maternal omentin levels were negatively correlated with insulin levels (r=-0.41, P=0.04) and positively correlated with insulin sensitivity (HOMA%S; r=0.4, P=0.04). Postpartum omentin levels were negatively correlated with maternal body mass index (r=-0.44, P=0.02). Median maternal omentin levels was comparable before and after delivery (57.2, inter-quartile range: 38.2-76.2 ng/mL vs. 53.4, 39.8-69.4 ng/mL, respectively, P=0.25) and highly correlated (r=0.83, Pinsulin resistance indices, suggesting that this adipokine may play a role in metabolic adaptations of normal gestation. The strong correlation between anteparum and postpartum maternal omentin levels, as well as the lack of association between maternal and neonatal omentin levels, suggest that placental or fetal compartments are unlikely as the main source of circulating maternal omentin.

Retroendocytosis of insulin in rat adipocytes

International Nuclear Information System (INIS)

Levy, J.R.; Olefsky, J.M.

1986-01-01

A variety of ligands internalized by receptor-mediated endocytosis follow a short circuit pathway that does not lead to degradation but results in rapid exocytosis of intact ligand, a process termed retroendocytosis. We studied the time course of [ 125 I]iodoinsulin processing and retroendocytosis after internalization in isolated rat adipocytes. After steady state binding and internalization, surface receptor-bound insulin was removed by exposing cells to a low pH at low temperatures. The cells containing internalized [ 125 I]iodoinsulin were reincubated in fresh medium; subsequently, the radioactivity remaining within the cells and released into the medium were analyzed at various times by trichloroacetic acid (TCA) precipitation, Sephadex G-50 gel filtration, and reverse phase HPLC. Cell-associated radioactivity progressively decreased after reincubation in 37 C buffer, with 50% released in 9 min and 85% by 45 min. In the media, TCA-precipitable material appeared quickly, with a t1/2 of 2 min, and plateaued by 10 min. TCA-soluble material was released continually throughout the 45-min period. The release of both TCA-precipitable and TCA-soluble material was temperature and energy dependent. Sephadex G-50 chromatography demonstrated the loss of insulin from the intracellular pool and its appearance in the medium with a time course similar to that of TCA-precipitable material. Reverse phase HPLC demonstrated that the intracellular and medium radioactivity eluting in peak II (insulin peak) on Sephadex G-50 was composed of both intact insulin and intermediates. After the internalization of insulin, rat adipocytes release not only small mol wt degradation products of insulin, but also insulin intermediates and intact insulin. The rate of retroendocytosis reported here is almost identical to the rate of insulin receptor recycling in rat adipocytes

Short-term effect of red wine (consumed during meals) on insulin requirement and glucose tolerance in diabetic patients.

Science.gov (United States)

Gin, H; Morlat, P; Ragnaud, J M; Aubertin, J

1992-04-01

To determine the effect of wine on insulin requirement or glucose tolerance. Five men with insulin-treated diabetes and 10 men with non-insulin-treated diabetes ate the same lunch with the same volume of either water or red wine (2 glasses). Insulin requirement was determined with an artificial pancreas (Biostator). Glucose tolerance was evaluated from the postprandial glycemic level. There was no significant difference in insulin requirement determined with an artificial pancreas in the insulin-treated patients after the two meals (31.5 +/- 4.21 U with water and 31.8 +/- 4.3 U with wine). Glucose tolerance in the non-insulin-treated patients was lower after the meal with wine. Moderate prandial wine consumption has no adverse effect on the glycemic control of diabetic patients. Thus, it appears unnecessary to proscribe the consumption of red wine in moderation with meals to diabetic patients. Wine contains tannins and phytates that can explain its action.

Mid-term results of bariatric surgery in morbidly obese Japanese patients with slow progressive autoimmune diabetes.

Science.gov (United States)

Uno, Kohei; Seki, Yosuke; Kasama, Kazunori; Wakamatsu, Kotaro; Hashimoto, Kenkichi; Umezawa, Akiko; Yanaga, Katsuhiko; Kurokawa, Yoshimochi

2017-12-11

Bariatric surgery is recognized as an effective treatment for type 2 diabetes mellitus, but data on its efficacy for type 1 diabetes mellitus, especially slowly progressive insulin-dependent diabetes mellitus, are limited. We investigated five Japanese patients with slowly progressive insulin-dependent diabetes mellitus who underwent bariatric surgery at our center. Five morbidly obese glutamic acid decarboxylase antibody-positive diabetic patients underwent two different types of bariatric surgery. The mean titer of anti-glutamic acid decarboxylase antibody was 4.6 U/mL, and the mean preoperative bodyweight and BMI were 113 kg and 39.6 kg/m 2 , respectively. The mean hemoglobin A1c was 8.4%. The mean fasting serum C-peptide was 5.0 ng/mL. Laparoscopic sleeve gastrectomy was performed in two patients, while laparoscopic sleeve gastrectomy with duodenojejunal bypass was performed in three patients. At one year after surgery, the mean bodyweight and BMI significantly dropped, and the mean percentage of excess weight loss was 96.4%. The mean hemoglobin A1c was 5.7%. This favorable trend was maintained at mid-term. Bariatric surgery for morbidly obese patients with anti-glutamic acid decarboxylase antibody-positive type 1 diabetes mellitus, especially slow progressive autoimmune diabetes, seemed effective in achieving mid-term glycemic control. Longer follow-up with a larger number of patients, as well as validation with more advanced patients with slowly progressive insulin-dependent diabetes mellitus, will be needed. © 2017 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

Long-term mortality after primary PCI for STEMI in patients with insulin-dependent diabetes mellitus

Directory of Open Access Journals (Sweden)

Zlatanović Petar

2015-01-01

Full Text Available Introduction: Primary PCI (pPCI is the gold standard in the treatment of patients with acute myocardial infarction (AMI with ST elevation (STEMI. Aim: The purpose of this study is to evaluate the influence of diabetic status upon arrival at five year survival in patients with STEMI that were treated with pPCI. Material and methods: Consecutive data for 2087 patients admitted in the period from 1st of January 2009. to 31st of December 2010. with diagnosis of acute STEMI were collected from catheterisation laboratory cardiology clinic CCS electronic database. Patients were divided into 3 groups: those without diabetes mellitus (DM, IDDM (insulin dependent diabetes mellitus, NIDDM (non-insulin dependent diabetes mellitus. Results: 1664 patients (79.7% did not have DM, 98 (4.7% had IDDM and 325 (15.6% had NIDDM. There was a statistically significant difference in mortality rate among three groups after 30 days, one year and five years after intervention, and the highest rates were recorded at the IDDM patients, then at the NIDDM and the lowest in patients without DM (15.3% vs 8.3% vs 5.9 %, p < 0.001 after 30 days; 21.4% vs 15.4% vs 10.9%, p < 0.001 after one year and 32.7% vs 24.3% vs 18%, p < 0.001 after 5 years. Also, there was a highly statistically significant difference in five-year mortality rate between patients with and without DM (26.2 % vs 17.6%, p < 0.001. IDDM was a independent factor when it comes to predicting five-year mortality (HR = 1.58, 95% CI 1.07-2.32, p = 0.02 whereas NIDDM was not (HR = 1.24, 95% CI 0.95-1.63, p = 0.12. Conclusion: Diabetic patients had an increased risk of mortality in the short and long-term follow-up after pPCI. Insulin-dependent was a single predicting factor after five year follow-up.

Effect of naloxone on plasma insulin, insulin-like growth factor I, and its binding protein 1 in patients with polycystic ovarian disease.

Science.gov (United States)

Laatikainen, T; Anttila, L; Suikkari, A M; Ruutiainen, K; Erkkola, R; Seppälä, M

1990-09-01

Insulin and insulin-like growth factors (IGFs) stimulate ovarian steroidogenesis, and hyperinsulinemia is often accompanied by hyperandrogenemia in women with polycystic ovarian disease (PCOD). Because opioid peptides are involved in the regulation of insulin secretion, we studied the effect of naloxone-induced opiate receptor blockade on the circulating levels of insulin, IGF-I, and IGF binding protein 1 (IGFBP-1) in 13 nonobese and 7 obese PCOD patients and in 6 healthy subjects. In obese PCOD patients, the mean basal insulin concentration was significantly higher and the IGFBP-1 concentration lower than in nonobese PCOD patients. Plasma IGF-I levels were elevated both in obese and nonobese PCOD patients. After an intravenous bolus of 10 mg naloxone, no significant changes were found in the circulating insulin or IGF-I levels, whereas IGFBP-1 levels decreased in nonobese PCOD patients and remained low in obese PCOD patients. No significant decrease was found in healthy subjects. These results suggest that, in addition to insulin, endogenous opioids are involved in the regulation of serum IGFBP-1 level.

Effect of strict metabolic control on regulation of subcutaneous blood flow in insulin-dependent diabetic patients

DEFF Research Database (Denmark)

Kastrup, J; Mathiesen, E R; Saurbrey, Nina

1987-01-01

washout technique. Mean arterial blood pressure was reduced by a maximum of 23 mmHg by elevating the limb above heart level and elevated to a maximum of 65 mmHg by head-up tilt; in the latter position venous pressure was kept constantly low by activation of the leg muscle vein pump (heel raising......The effect of 10 weeks of improved metabolic control on the impaired autoregulation of the subcutaneous blood flow was studied at the level of the lateral malleolus in eight long-term insulin-dependent diabetic patients with clinical microangiopathy. Blood flow was measured by the local 133-Xenon......). Improved metabolic control was achieved using either continuous subcutaneous insulin infusion or multiple insulin injections. The blood glucose concentration declined from (median) 12.7 to 6.8 mmol/l and the HbA1C level from 10.1 to 7.5% during strict metabolic control (p less than 0.01 and p less than 0...

Evidence-based insulin treatment in type 1 diabetes mellitus

DEFF Research Database (Denmark)

Jacobsen, Iben Brock; Henriksen, J E; Hother-Nielsen, O

2009-01-01

AIM: Evaluation of the evidence base for recommending different insulin treatment regimens in type 1 diabetes. METHODS: A computerised literature survey was conducted using The Cochrane Controlled Trials Register and the Pub Med database for the period of 1982-2007. RESULTS: A meta-analysis on only...... 49 out of 1295 references showed that CSII compared with conventional or multiple insulin injections therapy demonstrated a significant reduction in mean HbA1c (primary outcome) of 1.2% CI [0.73; 1.59] (P... daily insulin injections was based on only one publication demonstrating an improved quality of life but no significant reduction in HbA1c or hypoglycaemia. A comparison of rapid-acting insulin analogues and human soluble insulin demonstrated a statistically significant reduction in HbA1c of 0.1% CI: [0...

Mathematical modeling of the glucose-insulin system

DEFF Research Database (Denmark)

Palumbo, Pasquale; Ditlevsen, Susanne; Bertuzzi, Alessandro

2013-01-01

of pancreatic insulin production, with a oarser/finer level of detail ranging over cellular and subcellular scales, to short-term organ/tissue models accounting for the intra-venous and the oral glucose tolerance tests as well as for the euglycemic hyperinsulinemic clamp, to total-body, long-term diabetes...

Insulin receptors

International Nuclear Information System (INIS)

Kahn, C.R.; Harrison, L.C.

1988-01-01

This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

Autoimmunity in diabetics induced by hormonal contaminants of insulin

International Nuclear Information System (INIS)

Bloom, S.R.; Barnes, A.J.; Adrian, T.E.; Polak, J.M.

1979-01-01

Several commercial insulin preparations were found to contain significant quantities of pancreatic glucagon, pancreatic polypeptide (P.P.), vasoactive intestinal peptide (V.I.P.), and somatostatin, though these substances were effectively absent from the new highly purified or monocomponent insulins. Of 448 insulin-dependent diabetics receiving conventional insulins, 63% had circulating antibodies to human P.P., 6% antibodies to V.I.P., 6% to glucagon, and 0.5% to somatostatin. The antibodies were of high affinity and were commonest in the younger diabetics. No antibodies were detected in 167 maturity-onset diabetics, in 125 healthy controls, or in 22 patients treated only with monocomponent insulin. Immuno-cytochemical testing showed that antibody-positive diabetic plasmas reacted specifically against the corresponding hormone-producing pancreatic endocrine cells, against enteroglucagon and somatostatin cells outside the pancreas, and against V.I.P.-containing autonomic nerves throughout the body. The finding of iatrogenic autoimmunity to naturally occurring hormones in large numbers of insulin-dependent diabetics raises important questions about long-term treatment. (author)

Autoimmunity in diabetics induced by hormonal contaminants of insulin

Energy Technology Data Exchange (ETDEWEB)

Bloom, S R; Barnes, A J; Adrian, T E; Polak, J M [Royal Postgraduate Medical School, London (UK)

1979-01-06

Several commercial insulin preparations were found to contain significant quantities of pancreatic glucagon, pancreatic polypeptide (P.P.), vasoactive intestinal peptide (V.I.P.), and somatostatin, though these substances were effectively absent from the new highly purified or monocomponent insulins. Of 448 insulin-dependent diabetics receiving conventional insulins, 63% had circulating antibodies to human P.P., 6% antibodies to V.I.P., 6% to glucagon, and 0.5% to somatostatin. The antibodies were of high affinity and were commonest in the younger diabetics. No antibodies were detected in 167 maturity-onset diabetics, in 125 healthy controls, or in 22 patients treated only with monocomponent insulin. Immuno-cytochemical testing showed that antibody-positive diabetic plasmas reacted specifically against the corresponding hormone-producing pancreatic endocrine cells, against enteroglucagon and somatostatin cells outside the pancreas, and against V.I.P.-containing autonomic nerves throughout the body. The finding of iatrogenic autoimmunity to naturally occurring hormones in large numbers of insulin-dependent diabetics raises important questions about long-term treatment.

Efficacy of Metformin Versus Insulin in the Management of Pregnancy with Diabetes

International Nuclear Information System (INIS)

Waheed, S.; Malik, F.P.

2013-01-01

Objective: To compare the efficacy of metformin with insulin in the management of pregnancy with diabetes. Study Design: Randomized clinical trial. Place and Duration of Study: Department of Obstetrics and Gynaecology, Maternal and Child Health Centre (MCH), Pakistan Institute of Medical Sciences, Islamabad, from May 2010 to January 2011. Methodology: A total of 68 pregnant patients with diabetes were included in this study. Patients were randomly divided in to two groups of each 34 patients based on table of random numbers. One was labelled as group-A and other was labelled as group-B. Group-A received insulin and group-B received metformin for the management of diabetes. Results: The mean age was 29.82 A+- 4.58 and 29.35 A+- 4.97 years in groups-A and B respectively. Fasting blood sugar level after 1 month was controlled in 22 (64.7%) patients in group-A and in 27 (79.4%) in group-B (p > 0.05). Fasting blood sugar level at term, remained controlled in 30 (88.2%) patients in group-A and 27 (79.4%) in group-B (p > 0.05). Comparison of random blood sugar levels within normal limits after 1 month in 25 (73.5%) in group-A and in 24 (70.6%) in group-B. At term, random blood sugar level was controlled in 28 (82.4%) and 27 (79.4%) patients in group-A and B, respectively. Comparison of post-treatment HBA1C level depicts that diabetes controlled in 27 (79.4%) patients in group-A while in 28 (82.3%) patients of group-B. The efficacy of metformin and insulin in controlling diabetes was equal in two groups. Conclusion: There was no marked difference in efficacy of metformin and insulin in controlling diabetes in pregnant patients in two groups. (author)

Efficacy of metformin versus insulin in the management of pregnancy with diabetes.

Science.gov (United States)

Waheed, Seema; Malik, Farhat Perveen; Mazhar, Syeda Batool

2013-12-01

To compare the efficacy of metformin with insulin in the management of pregnancy with diabetes. Randomized clinical trial. Department of Obstetrics and Gynaecology, Maternal and Child Health Centre (MCH), Pakistan Institute of Medical Sciences, Islamabad, from May 2010 to January 2011. A total of 68 pregnant patients with diabetes were included in this study. Patients were randomly divided in to two groups of each 34 patients based on table of random numbers. One was labelled as group-A and other was labelled as group-B. Group-A received insulin and group-B received metformin for the management of diabetes. The mean age was 29.82 ± 4.58 and 29.35 ± 4.97 years in groups-A and B respectively. Fasting blood sugar level after 1 month was controlled in 22 (64.7%) patients in group-A and in 27 (79.4%) in group-B (p > 0.05). Fasting blood sugar level at term, remained controlled in 30 (88.2%) patients in group-A and 27 (79.4%) in group-B (p > 0.05). Comparison of random blood sugar levels within normal limits after 1 month in 25 (73.5%) in group-A and in 24 (70.6%) in group-B. At term, random blood sugar level was controlled in 28 (82.4%) and 27 (79.4%) patients in group-A and B, respectively. Comparison of post-treatment HBA1C level depicts that diabetes controlled in 27 (79.4%) patients in group-A while in 28 (82.3%) patients of group-B. The efficacy of metformin and insulin in controlling diabetes was equal in two groups. There was no marked difference in efficacy of metformin and insulin in controlling diabetes in pregnant patients in two groups.

Studies on insulin receptor, 2. Studies on the influence of starvation and high fat diet on insulin receptor

Energy Technology Data Exchange (ETDEWEB)

Sakai, Y [Hiroshima Univ. (Japan). School of Medicine

1979-08-01

The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using /sup 125/I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and /sup 125/I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and /sup 125/I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in /sup 125/I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia.

Ultrastructural evidence for the accumulation of insulin in nuclei of intact 3T3-L1 adipocytes by an insulin-receptor mediated process

International Nuclear Information System (INIS)

Smith, R.M.; Jarett, L.

1987-01-01

Monomeric ferritin-labeled insulin (F/sub m/-Ins), a biologically active, electron-dense marker of occupied insulin receptors, was used to characterize the internalization of insulin in 3T3-L1 adipocytes. F/sub m/-Ins bound specifically to insulin receptors and was internalized in a time- and temperature-dependent manner. In the nucleus, several F/sub m/-Ins particles usually were found in the same general location-near nuclear pores, associated with the periphery of the condensed chromatin. Addition of a 250-fold excess of unlabeled insulin or incubation at 15 0 C reduced the number of F/sub m/-Ins particles found in nuclei after 90 min by 99% or 92%, respectively. Nuclear accumulation of unlabeled ferritin was only 2% of that found with F/sub m/-Ins after 90 min at 37 0 C. Biochemical experiments utilizing 125 I-labeled insulin and subcellular fractionation indicated that intact 3T3-L1 adipocytes internalized insulin rapidly and that ≅ 3% of the internalized ligand accumulated in nuclei after 1 hr. These data provide biochemical and high-resolution ultrastructural evidence that 3T3-L1 adipocytes accumulate potentially significant amounts of insulin in nuclei by an insulin receptor-mediated process. The transport of insulin or the insulin-receptor complex to nuclei in this cell or in others may be directly involved in the long-term biological effects of insulin - in particular, in the control of DNA and RNA synthesis

MEANING TRANSFER ANALYSIS OF BALINESE ARTS TERMS INTO ENGLISH AND FRENCH: A COMPARATIVE STUDY

Directory of Open Access Journals (Sweden)

Putu Weddha Savitri

2015-11-01

Full Text Available In order to show and promote Balinese culture to the incoming tourists, many specific terms, especially in arts terms, must be well translated. This paper aims at analyzing the meaning transfer of Balinese Arts Terms into English and French found in Tourism Promotion Book published by Bali Government Tourism Department in two languages versions. The analysis focused on the techniques or procedures applied in transferring Balinese art terms into English (TL1 and French (TL2. Besides, it is also to figure out the most common technique used by the translator in transferring the meanings. The findings showed that there are three techniques used to transfer the meaning of the SL into the TL 1, those are descriptive, transcription, and functional equivalence, meanwhile, there are three translation techniques: transcription, functional equivalence, and formal equivalence and one translation procedure: cultural equivalence used in transferring the SL meaning to TL 2. Transcription technique, usually called borrowing was mostly used by the translator in the meaning transfer from the SL to both the target languages in order to retain the SL meaning in the TL.

Partial sleep restriction decreases insulin sensitivity in type 1 diabetes

NARCIS (Netherlands)

Donga, Esther; van Dijk, Marieke [Leiden Univ., LUMC; van Dijk, J. Gert; Biermasz, Nienke R.; Lammers, Gert-Jan; van Kralingen, Klaas; Hoogma, Roel P. L. M.; Corssmit, Eleonora P. M.; Romijn, Johannes A.

2010-01-01

Sleep restriction results in decreased insulin sensitivity and glucose tolerance in healthy subjects. We hypothesized that sleep duration is also a determinant of insulin sensitivity in patients with type 1 diabetes. We studied seven patients (three men, four women) with type 1 diabetes: mean age 44

Birth-weight, insulin levels, and HOMA-IR in newborns at term

Directory of Open Access Journals (Sweden)

Simental-Mendía Luis E

2012-07-01

Full Text Available Abstract Background Recent studies have demonstrated that low and high birth-weight at birth are risk factors of developing diabetes. The aim of this study was to determine if the abnormal birth-weight is related with hyperinsulinemia and elevated index of the Homeostasis Model assessment for Insulin Resistance (HOMA-IR at birth, in at term newborns. Methods Newborns with gestational age between 38 and 41 weeks, products of normal pregnancies of healthy mothers aged 18 to 39 years, were eligible to participate. Small-for-gestational age (SGA and large-for-gestational age (LGA newborns were compared with appropriate-for-gestational (AGA age newborns. Incomplete or unclear data about mother’s health status, diabetes, gestational diabetes, history of gestational diabetes, hypertension, pre-eclampsia, eclampsia, and other conditions that affect glucose metabolism were exclusion criteria. Hyperinsulinemia was defined by serum insulin levels ≥13.0 μU/mL and IR by HOMA-IR ≥2.60. Multiple logistic regression analysis was used to determine the odds ratio (OR that computes the association between birth-weight (independent variable with hyperinsulinemia and HOMA-IR index (dependent variables. Results A total of 107 newborns were enrolled; 13, 22, and 72 with SGA, LGA, and AGA, respectively. Hyperinsulinemia was identified in 2 (15.4%, 6 (27.3%, and 5 (6.9% with SGA, LGA, and AGA (p=0.03, whereas IR in 3 (23.1%, 8 (36.4%, and 10 (13.9% newborns with SGA, LGA and AGA (p=0.06. The LGA showed a strong association with hyperinsulinemia (OR 5.02; CI 95%, 1.15-22.3; p=0.01 and HOMA-IR (OR 3.54; CI 95%, 1.03-12.16; p=0.02; although without statistical significance, the SGA showed a tendency of association with hyperinsulinemia (OR 2.43; CI 95%, 0.43-17.3 p=0.29 and HOMA-IR (OR 1.86; CI 95%, 0.33-9.37; p=0.41. Conclusions Our results suggest that LGA is associated with hyperinsulinemia and elevated HOMA-IR at birth whereas the SGA show a tendency of

Improved insulin sensitivity after exercise: focus on insulin signaling

DEFF Research Database (Denmark)

Frøsig, Christian; Richter, Erik

2009-01-01

After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part...... of the mechanism relates to an improved ability of insulin to stimulate translocation of glucose transporters (GLUT4) to the muscle membrane after exercise. How this is accomplished is still unclear; however, an obvious possibility is that exercise interacts with the insulin signaling pathway to GLUT4...... translocation allowing for a more potent insulin response. Parallel to unraveling of the insulin signaling cascade, this has been investigated within the past 25 years. Reviewing existing studies clearly indicates that improved insulin action can occur independent of interactions with proximal insulin signaling...

Intermittent hypoxia increases insulin resistance in genetically obese mice.

Science.gov (United States)

Polotsky, Vsevolod Y; Li, Jianguo; Punjabi, Naresh M; Rubin, Arnon E; Smith, Philip L; Schwartz, Alan R; O'Donnell, Christopher P

2003-10-01

Obstructive sleep apnoea, a syndrome that leads to recurrent intermittent hypoxia, is associated with insulin resistance in obese individuals, but the mechanisms underlying this association remain unknown. We utilized a mouse model to examine the effects of intermittent hypoxia on insulin resistance in lean C57BL/6J mice and leptin-deficient obese (C57BL/6J-Lepob) mice. In lean mice, exposure to intermittent hypoxia for 5 days (short term) resulted in a decrease in fasting blood glucose levels (from 173 +/- 11 mg dl-1 on day 0 to 138 +/- 10 mg dl-1 on day 5, P obese mice, short-term intermittent hypoxia led to a decrease in blood glucose levels accompanied by a 607 +/- 136 % (P intermittent hypoxia was completely abolished by prior leptin infusion. Obese mice exposed to intermittent hypoxia for 12 weeks (long term) developed a time-dependent increase in fasting serum insulin levels (from 3.6 +/- 1.1 ng ml-1 at baseline to 9.8 +/- 1.8 ng ml-1 at week 12, P intermittent hypoxia is dependent on the disruption of leptin pathways.

26 CFR 48.4161(b)-2 - Meaning of terms.

Science.gov (United States)

2010-04-01

... EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Sporting Goods § 48.4161(b)-2 Meaning of terms. (a... with the particular type of arrow shaft. (b) Parts and accessories—(1) In general. “Parts and... attachment to, a bow or arrow of the type described in section 4161(b)(1) and paragraph (a) of this section...

Statin Intake Is Associated With Decreased Insulin Sensitivity During Cardiac Surgery

Science.gov (United States)

Sato, Hiroaki; Carvalho, George; Sato, Tamaki; Hatzakorzian, Roupen; Lattermann, Ralph; Codere-Maruyama, Takumi; Matsukawa, Takashi; Schricker, Thomas

2012-01-01

OBJECTIVE Surgical trauma impairs intraoperative insulin sensitivity and is associated with postoperative adverse events. Recently, preprocedural statin therapy is recommended for patients with coronary artery disease. However, statin therapy is reported to increase insulin resistance and the risk of new-onset diabetes. Thus, we investigated the association between preoperative statin therapy and intraoperative insulin sensitivity in nondiabetic, dyslipidemic patients undergoing coronary artery bypass grafting. RESEARCH DESIGN AND METHODS In this prospective, nonrandomized trial, patients taking lipophilic statins were assigned to the statin group and hypercholesterolemic patients not receiving any statins were allocated to the control group. Insulin sensitivity was assessed by the hyperinsulinemic-normoglycemic clamp technique during surgery. The mean, SD of blood glucose, and the coefficient of variation (CV) after surgery were calculated for each patient. The association between statin use and intraoperative insulin sensitivity was tested by multiple regression analysis. RESULTS We studied 120 patients. In both groups, insulin sensitivity gradually decreased during surgery with values being on average ∼20% lower in the statin than in the control group. In the statin group, the mean blood glucose in the intensive care unit was higher than in the control group (153 ± 20 vs. 140 ± 20 mg/dL; P statin group (SD, P statin use was independently associated with intraoperative insulin sensitivity (β = −0.16; P = 0.03). CONCLUSIONS Preoperative use of lipophilic statins is associated with increased insulin resistance during cardiac surgery in nondiabetic, dyslipidemic patients. PMID:22829524

Effect of exercise on insulin action in human skeletal muscle

DEFF Research Database (Denmark)

Richter, Erik; Mikines, K J; Galbo, Henrik

1989-01-01

The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization...... was performed. Increased insulin action on glucose uptake was found in the exercised compared with the rested thigh at mean plasma insulin concentrations of 23, 40, and 410 microU/ml. Furthermore, prior contractions directed glucose uptake toward glycogen synthesis and increased insulin effects on thigh O2...... consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp...

Relationship of serum resistin with insulin resistance and obesity

International Nuclear Information System (INIS)

Zaidi, S.I.Z.

2015-01-01

Background: Adipokines have been implicated in the modulation of insulin sensitivity and glucose tolerance and have thus gained importance in the study of Type 2 diabetes mellitus (T2DM). Resistin, a unique signalling molecule, is being proposed as a significant factor in the pathogenesis of obesity-related insulin resistance. However, its relevance to human diabetes mellitus remains uncertain and controversial. This study was therefore planned to compare and correlate the potential role of resistin in obese patients with T2DM and obese non-diabetic controls and also to evaluate the correlation between resistin and marker of obesity and glycaemic parameters. Method: Fasting serum resistin, glucose and insulin were measured in forty obese diabetics (mean±SD BMI 35±5 kg/m2) and forty obese non-diabetics (mean±SD BMI 33±3 kg/m2). Insulin resistance was assessed using the HOMA-IR formula derived from fasting insulin and glucose levels. Results: Serum resistin levels (38±8 ng/ml) were significantly higher in type 2 diabetic patients as compared with the controls. Fasting blood glucose (164±46 mg/dl), serum insulin (37±7 μU/ml) and insulin resistance (19±8), were considerably higher among the studied diabetics than in the controls. Pearson's correlation analysis revealed positive correlation between serum resistin and BMI (p=0.001) and HOMA-IR (p=0.561) in diabetic subjects. Similarly, a correlation also existed between serum resistin and BMI (p=0.016) and HOMA-IR (p=0.307) in control obese subjects. However, it was highly significant in diabetics as compared to non-diabetic controls. Conclusion: A significant BMI-dependent association exists between resistin and insulin resistance in patients with T2DM. It appears that resistin may play a role in the pathogenesis of obesity and insulin resistance and that both of these may contribute to the development of T2DM. (author)

Pulse radiolysis study of zinc(II)-insulin

Energy Technology Data Exchange (ETDEWEB)

Elliot, A J; Wilkinson, F; Armstrong, D A [Calgary Univ., Alberta (Canada). Dept. of Chemistry

1980-07-01

Reactions of e/sup -/sub(aq) with zinc(II)-insulin at pH 6.6 and 9.0 yielded relatively low disulphide anion absorptions, suggesting e/sup -/sub(aq) reacts at other sites than S-S. A similar conclusion was reached for the reaction of COsub(./2) where an even lower yield of disulphide anion was found. However, here the disulphide anion yield increased with 'prepulsing'. Simultaneously the rate constant decreased, implying that a more reactive site was 'cleaned up'. While no reaction of Brsub(./2) with insulin was observed, both OH and Clsub(./2) reacted rapidly and predominantly at the tyrosine residues. The second order rate constants, calculated in terms of insulin monomer concentrations, are reported for e/sup -/sub(aq) COsub(./2) and Clsub(./2). The transient spectra qualitatively support evidence regarding the accessibility of S-S bonds and tyrosine residues in the various forms of insulin as predicted from earlier studies.

14 CFR 331.3 - What do the terms used in this part mean?

Science.gov (United States)

2010-01-01

... part mean? The following terms apply to this part: Airport means Ronald Reagan Washington National... generally permitted at Ronald Reagan Washington National Airport; until November 30, 2005 at Washington...

Comparison of Insulin Detemir and Insulin Glargine for Hospitalized Patients on a Basal-Bolus Protocol

Directory of Open Access Journals (Sweden)

Sondra Davis

2017-04-01

Full Text Available BACKGROUND: The primary purpose of this study is to determine whether insulin detemir is equivalent to insulin glargine in controlling hyperglycemia for the adult hospitalized patient on a basal-bolus treatment regimen. METHODS: A retrospective study was conducted at two acute care hospitals within the same health system. Patients from both facilities who were initiated on a basal-bolus subcutaneous insulin regimen were included in the study. The basal-bolus regimen consisted of three components: basal, bolus, and corrective insulin with only the data from the first seven days analyzed. Once the basal-bolus protocol was initiated, all previous glycemic agents were discontinued. The target glycemic goal of the study was 100–180 mg/dL. RESULTS: In both groups, 50% of the patients had achieved the target glycemic control goal (100–180 mg/dL by day 2 (p = 0.3. However, on the seventh or last day of basal-bolus treatment, whichever came first, 36.36% of patients receiving insulin detemir (n = 88 achieved the blood glucose reading goal compared to 52.00% in patients receiving insulin glargine (n = 100 (p = 0.03. This corresponded to an adjusted odds ratio of 2.12 (1.08 to 4.15, p = 0.03. The adjusting variables were provider type, whether the patient was hospitalized within 30 days prior and diagnosis of stroke. The mean blood glucose readings for the insulin glargine and the insulin detemir groups while on basal-bolus therapy were 200 mg/dL and 215 mg/dL, respectively (p = 0.05. The total number of blood glucose readings less than 70 mg/dL and less than 45 mg/dL was very low and there were no differences in number of episodes with hypoglycemia between the two groups. CONCLUSION: There was not a statistical difference between the two groups at 2 days, however there was on the seventh day or the last day of basal-bolus treatment. There were nonsignificant hypoglycemia events between basal insulin groups and the results for the last or seventh day

Insulin binding properties of normal and transformed human epidermal cultured keratinocytes

International Nuclear Information System (INIS)

Verrando, P.; Ortonne, J.P.

1985-01-01

Insulin binding to its receptors was studied in cultured normal and transformed (A431 line) human epidermal keratinocytes. The specific binding was a temperature-dependent, saturable process. Normal keratinocytes possess a mean value of about 80,000 receptors per cell. Fifteen hours exposure of the cells to insulin lowered their receptor number (about 65% loss in available sites); these reappeared when the hormone was removed from the culture medium. In the A431 epidermoid carcinoma cell line, there is a net decrease in insulin binding (84% of the initial bound/free hormone ratio in comparison with normal cells) essentially related to a loss in receptor affinity for insulin. Thus, cultured human keratinocytes which express insulin receptors may be a useful tool in understanding skin pathology related to insulin disorders

Acute pain induces insulin resistance in humans

DEFF Research Database (Denmark)

Greisen, J.; Juhl, C.B.; Grøfte, Thorbjørn

2001-01-01

Background: Painful trauma results in a disturbed metabolic state with impaired insulin sensitivity, which is related to the magnitude of the trauma. The authors explored whether pain per se influences hepatic and extrahepatic actions of insulin. Methods: Ten healthy male volunteers underwent two...... randomly sequenced hyperinsulinemic–euglycemic (insulin infusion rate, 0.6 mU · kg-1 · min-1 for 180 min) clamp studies 4 weeks apart. Self-controlled painful electrical stimulation was applied to the abdominal skin for 30 min, to a pain intensity of 8 on a visual analog scale of 0–10, just before...... the clamp procedure (study P). In the other study, no pain was inflicted (study C). Results: Pain reduced whole-body insulin-stimulated glucose uptake from 6.37 ± 1.87 mg · kg-1 · min-1 (mean ± SD) in study C to 4.97 ± 1.38 mg · kg-1 · min-1 in study P (P

Effects of supervised structured aerobic exercise training program on fasting blood glucose level, plasma insulin level, glycemic control, and insulin resistance in type 2 diabetes mellitus.

Science.gov (United States)

Shakil-Ur-Rehman, Syed; Karimi, Hossein; Gillani, Syed Amir

2017-01-01

To determine the effects of supervised structured aerobic exercise training (SSAET) program on fasting blood glucose level (FBGL), plasma insulin level (PIL), glycemic control (GC), and insulin resistance (IR) in type 2 diabetes mellitus (T2DM). Riphah Rehabilitation and Research Centre (RRRC) was the clinical setting for this randomized controlled trial, located at Pakistan Railways General Hospital (PRGH), Rawalpindi, Pakistan. Study duration was 18 months from January 1, 2015 to June 30, 2016. Patients of both genders ranging 40-70 years of age with at least one year of history of T2DM were considered eligible according to WHO criteria, while patients with other chronic diseases, history of smoking, regular exercise and diet plan were excluded. Cohorts of 195 patients were screened out of whom 120 fulfilled the inclusion criteria. Amongst them 102 agreed to participate and were assigned to experimental (n=51) and control (n=51) groups. Experimental group underwent SSAET program, routine medication and dietary plan, whereas the control group received routine medication and dietary plan, while both group received treatment for 25 weeks. The blood samples were taken at baseline and on the completion of 25 weeks. The investigation of fasting blood glucose level, plasma insulin level, and glycemic control was conducted to calculate IR. Patients with T2DM in experimental group (n=51) treated with SSAET program, routine medication and dietary plan significantly improved FBGL (pre-mean= 276.41±25.31, post-mean=250.07±28.23), PIL (pre-mean=13.66±5.31, post-mean=8.91±3.83), GC (pre-mean=8.31±1.79, post-mean 7.28±1.43), and IR (pre-mean=64.95±27.26, post-mean 37.97±15.58), as compared with patients in control group treated with routine medication and dietary plan in whom deteriorations were noted in FBGL (pre-mean=268.19±22.48, post-mean=281.41±31.30), PIL(pre-mean=14.14±5.48, post-mean=14.85±5.27) GC (pre-mean=8.15±1.74, post-mean=8.20±1.44, and IR (pre-mean

Carbohydrate modified diet & insulin sensitizers reduce body weight & modulate metabolic syndrome measures in EMPOWIR (enhance the metabolic profile of women with insulin resistance: a randomized trial of normoglycemic women with midlife weight gain.

Directory of Open Access Journals (Sweden)

Harriette R Mogul

Full Text Available Progressive midlife weight gain is associated with multiple adverse health outcomes and may represent an early manifestation of insulin resistance in a distinct subset of women. Emerging data implicate hyperinsulinema as a proximate cause of weight gain and support strategies that attenuate insulin secretion.To assess a previously reported novel hypocaloric carbohydrate modified diet alone (D, and in combination with metformin (M and metformin plus low-dose rosiglitazone (MR, in diverse women with midlife weight gain (defined as >20lbs since the twenties, normal glucose tolerance, and hyperinsulinemia.46 women, mean age 46.6±1.0, BMI 30.5±0.04 kg/m2, 54.5% white, 22.7% black, 15.9% Hispanic, at 2 university medical centers.A dietary intervention designed to reduce insulin excursions was implemented in 4 weekly nutritional group workshops prior to randomization.Change in 6-month fasting insulin. Pre-specified secondary outcomes were changes in body weight, HOMA-IR, metabolic syndrome (MS measures, leptin, and adiponectin.Six-month fasting insulin declined significantly in the M group: 12.5 to 8.0 µU/ml, p = .026. Mean 6-month weight decreased significantly and comparably in D, M, and MR groups: 4.7, 5.4, and 5.5% (p's.049, .002, and.032. HOMA-IR decreased in M and MR groups (2.5 to 1.6 and 1.9 to 1.3, p's = .054, .013. Additional improvement in MS measures included reduced waist circumference in D and MR groups and increased HDL in the D and M groups. Notably, mean fasting leptin did not decline in a subset of subjects with weight loss (26.15±2.01 ng/ml to 25.99±2.61 ng/ml, p = .907. Adiponectin increased significantly in the MR group (11.1±1.0 to 18.5±7.4, p<.001 Study medications were well tolerated.These findings suggest that EMPOWIR's easily implemented dietary interventions, alone and in combination with pharmacotherapies that target hyperinsulinemia, merit additional investigation in larger, long-term studies

Glucose-Responsive Implantable Polymeric Microdevices for "Smart" Insulin Therapy of Diabetes

Science.gov (United States)

Chu, Michael Kok Loon

Diabetes mellitus is a chronic illness manifested by improper blood glucose management, affecting over 350 million worldwide. As a result, all type 1 patients and roughly 20% of type 2 patients require exogenous insulin therapy to survive. Typically, daily multiple injections are taken to maintain normal glucose levels in response glucose spikes from meals. However, patient compliance and dosing accuracy can fluctuate with variation in meals, exercise, glucose metabolism or stress, leading to poor clinical outcomes. A 'smart', closed-loop insulin delivery system providing on-demand release kinetics responding to circulating glucose levels would be a boon for diabetes patients, replacing constant self monitoring and insulin. This thesis focuses on the development of a novel, 'smart' insulin microdevice that can provide on-demand insulin release in response to blood glucose levels. In the early stage, the feasibility of integrating a composite membrane with pH-responsive nanoparticles embedded in ethylcellulose membrane to provide pH-responsive in vitro release was examined and confirmed using a model drug, vitamin B12. In the second microdevice, glucose oxidase for generating pH signals from glucose oxidation, catalase and manganese dioxide nanoparticles, as peroxide scavengers, were used in a bioinorganic, albumin-based membrane cross-linked with a polydimethylsiloxane (PDMS) grid-microdevice system. This prototype device demonstrated insulin release in response to glucose levels in vitro and regulating plasma glucose in type 1 diabetic rats when implanted intraperitoneally. Advancement allowing for subcutaneous implantation and improved biocompatibility was achieved with surface modification of PDMS microdevices grafted with activated 20 kDa polyethylene glycol (PEG) chains, dramatically reducing immune response and local inflammation. When implanted subcutaneously in diabetic rats, glucose-responsive insulin delivery microdevices showed short and long-term

XPS and Raman study of zinc containing silica microparticles loaded with insulin

Energy Technology Data Exchange (ETDEWEB)

Vanea, E.; Simon, V., E-mail: viorica.simon@phys.ubbcluj.ro

2013-09-01

Zinc–silica microparticles obtained by sol–gel method solely or by combining sol–gel chemistry with freeze-drying and spray-drying procedures were explored as potential insulin drug delivery carriers for their improved loading efficiency. Zinc containing silica hosts of different specific surface area and mean pore volume loaded with insulin under similar conditions were investigated by X-ray photoelectron spectroscopy (XPS) and confocal micro-Raman spectroscopy in order to assess the insulin adherence to these matrices and the biologically active state of the insulin after embedding.

High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity.

Directory of Open Access Journals (Sweden)

Zhigang Liu

Full Text Available High-fat diet (HFD-induced obesity is associated with insulin resistance, which may affect brain synaptic plasticity through impairment of insulin-sensitive processes underlying neuronal survival, learning, and memory. The experimental model consisted of 3 month-old C57BL/6J mice fed either a normal chow diet (control group or a HFD (60% of calorie from fat; HFD group for 12 weeks. This model was characterized as a function of time in terms of body weight, fasting blood glucose and insulin levels, HOMA-IR values, and plasma triglycerides. IRS-1/Akt pathway was assessed in primary hepatocytes and brain homogenates. The effect of HFD in brain was assessed by electrophysiology, input/output responses and long-term potentiation. HFD-fed mice exhibited a significant increase in body weight, higher fasting glucose- and insulin levels in plasma, lower glucose tolerance, and higher HOMA-IR values. In liver, HFD elicited (a a significant decrease of insulin receptor substrate (IRS-1 phosphorylation on Tyr608 and increase of Ser307 phosphorylation, indicative of IRS-1 inactivation; (b these changes were accompanied by inflammatory responses in terms of increases in the expression of NFκB and iNOS and activation of the MAP kinases p38 and JNK; (c primary hepatocytes from mice fed a HFD showed decreased cellular oxygen consumption rates (indicative of mitochondrial functional impairment; this can be ascribed partly to a decreased expression of PGC1α and mitochondrial biogenesis. In brain, HFD feeding elicited (a an inactivation of the IRS-1 and, consequentially, (b a decreased expression and plasma membrane localization of the insulin-sensitive neuronal glucose transporters GLUT3/GLUT4; (c a suppression of the ERK/CREB pathway, and (d a substantial decrease in long-term potentiation in the CA1 region of hippocampus (indicative of impaired synaptic plasticity. It may be surmised that 12 weeks fed with HFD induce a systemic insulin resistance that impacts

Cost-effectiveness of continuous subcutaneous insulin infusion versus multiple daily injections of insulin in Type 1 diabetes

DEFF Research Database (Denmark)

Roze, S.; Smith-Palmer, J.; Valentine, W.

2015-01-01

Aim: Continuous subcutaneous insulin infusion (CSII) is increasingly used in clinical practice for the management of selected patients with Type 1 diabetes. Several cost-effectiveness studies comparing CSII vs. multiple insulin injections (MDI) have been reported. The aim was systematically...... to review these analyses and test the hypothesis that CSII is a cost-effective use of healthcare resources across settings. Methods: A literature review was performed using MEDLINE, Cochrane Library and other databases. No time limit or language restrictions were applied. After two rounds of screening, 11...... cost-effectiveness analyses were included in the final review, of which nine used the CORE Diabetes Model. A narrative synthesis was conducted and mean cost effectiveness calculated. Results: CSII was considered cost-effective vs. MDI in Type 1 diabetes in all 11 studies in 8 countries, with a mean (95...

RELATIONSHIP BETWEEN URIC ACID METABOLISM AND INSULIN RESISTANCE

OpenAIRE

辻本, 伸宏; 金内, 雅夫; 尾崎, 博基; 藤田, 泰三; 中嶋, 民夫; 土肥, 和紘

1998-01-01

To investigate the relationship between uric acid (UA) metabolism and insulin resistance, serum creatinine concentration (Scr), serum UA concentration (SuA) and the urinary excretion of creatinine and UA were determined in 25 non-diabetic patients. Creatinine clearance (Ccr) and UA clearance/creatinine clearance ratio (CuA/Ccr) were also calculated. Insulin resistance was evaluated by the euglycemic glucose clamp tech- nique and expressed as the mean value of the glucose infusion rate (M-valu...

Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line

International Nuclear Information System (INIS)

Androlewicz, M.J.; Straus, D.S.; Brandenburg, D.F.

1989-01-01

Previous studies from this laboratory demonstrated that the PG19 mouse melanoma cell line does not exhibit a biological response to insulin, whereas melanoma x mouse embryo fibroblast hybrids do respond to insulin. To investigate the molecular basis of the insulin resistance of the PG19 melanoma cells, insulin receptors from the insulin-resistant melanoma cells and insulin-sensitive fibroblast x melanoma hybrid cells were analyzed by the technique of photoaffinity labeling using the photoprobe 125 I-NAPA-DP-insulin. Photolabeled insulin receptors from the two cell types have identical molecular weights as determined by SDS gel electrophoresis under reducing and nonreducing conditions, indicating that the receptors on the two cell lines are structurally similar. Insulin receptor internalization studies revealed that the hybrid cells internalize receptors to a high degree at 37 degree C, whereas the melanoma cells internalize receptors to a very low degree or not at all. The correlation between ability to internalize insulin receptors and sensitivity to insulin action in this system suggests that uptake of the insulin-receptor complex may be required for insulin action in these cells. Insulin receptors from the two cell lines autophosphorylate in a similar insulin-dependent manner both in vitro and in intact cells, indicating that insulin receptors on the melanoma and hybrid cells have functional tyrosine protein kinase activity. Therefore, the block in insulin action in the PG19 melanoma cells appears to reside at a step beyond insulin-stimulated receptor autophosphorylation

Effect of Scoparia dulcis extract on insulin receptors in streptozotocin induced diabetic rats: studies on insulin binding to erythrocytes.

Science.gov (United States)

Pari, Leelavinothan; Latha, Muniappan; Rao, Chippada Appa

2004-01-01

We investigated the insulin-receptor-binding effect of Scoparia dulcis plant extract in streptozotocin (STZ)-induced male Wistar rats, using circulating erythrocytes (ER) as a model system. An aqueous extract of S dulcis plant (SPEt) (200 mg/kg body weight) was administered orally. We measured blood levels of glucose and plasma insulin and the binding of insulin to cell-membrane ER receptors. Glibenclamide was used as standard reference drug. The mean specific binding of insulin to ER was significantly lower in diabetic control rats (DC) (55.0 +/- 2.8%) than in SPEt-treated (70.0 +/- 3.5%)- and glibenclamide-treated (65.0 +/- 3.3%) diabetic rats, resulting in a significant decrease in plasma insulin. Scatchard plot analysis demonstrated that the decrease in insulin binding was accounted for by a lower number of insulin receptor sites per cell in DC rats when compared with SPEt- and glibenclamide-treated rats. High-affinity (Kd1), low-affinity (Kd2), and kinetic analysis revealed an increase in the average receptor affinity in ER from SPEt and glibenclamide treated diabetic rats having 2.5 +/- 0.15 x 10(10) M(-1) (Kd1); 17.0 +/- 1.0 x 10(-8) M(-1) (Kd2), and 2.0 +/- 0.1 x 10(-10) M(-1) (Kd1); 12.3 +/- 0.9 x 10(-8) M(-1) (Kd2) compared with 1.0 +/- 0.08 x 10(-10) M(-1) (Kd1); 2.7 +/- 0.25 x 10(-8) M(-1) (Kd2) in DC rats. The results suggest an acute alteration in the number of insulin receptors on ER membranes in STZ-induced diabetic rats. Treatment with SPEt and glibenclamide significantly improved specific insulin binding, with receptor number and affinity binding (p < 0.001) reaching almost normal non-diabetic levels. The data presented here show that SPEt and glibenclamide increase total ER membrane insulin binding sites with a concomitant significant increase in plasma insulin.

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

Directory of Open Access Journals (Sweden)

Nicole M. Templeman

2017-07-01

Full Text Available The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1 signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.

Science.gov (United States)

Templeman, Nicole M; Flibotte, Stephane; Chik, Jenny H L; Sinha, Sunita; Lim, Gareth E; Foster, Leonard J; Nislow, Corey; Johnson, James D

2017-07-11

The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2 +/- mice to Ins2 +/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2 +/- mice. Halving Ins2 lowered circulating insulin by 25%-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study.

Science.gov (United States)

But, Anna; De Bruin, Marie L; Bazelier, Marloes T; Hjellvik, Vidar; Andersen, Morten; Auvinen, Anssi; Starup-Linde, Jakob; Schmidt, Marjanka K; Furu, Kari; de Vries, Frank; Karlstad, Øystein; Ekström, Nils; Haukka, Jari

2017-09-01

The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies. National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5-1, 1-2, 2-3, 3-4, 4-5, 5-6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin. A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for ≤0.5 years of treatment and for malignant melanoma for 2-3 years (RR 1.92, 95% CI 1.02, 3.61) and 4-5 years (RR 3.55, 95% CI 1.68, 7.47]); among men, a lower risk was observed for pancreatic cancer for 2-3 years (RR 0.34, 95% CI 0.17, 0.66) and for liver cancer for 3-4 years (RR 0.36, 95% CI 0.14, 0.94) and >6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences. The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.

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.

Peripheral nerve function during hyperglycemic clamping in insulin-dependent diabetic patients

DEFF Research Database (Denmark)

Sindrup, S H; Ejlertsen, B; Gjessing, H

1989-01-01

The influence of hyperglycemia on peripheral nerve function was studied in 9 patients with long-term insulin-dependent diabetes. Blood glucose concentration was raised 13.5 +/- 0.5 mmol/l (mean +/- SEM) within 15 min and kept approximately 15 mmol/l over basal level for 120 min by intravenous...... glucose infusion. Hyperglycemia was accompanied by increased plasma osmolality. Sensory and motor nerve conduction and distal motor latency in the ulnar nerve were determined before, immediately after induction of hyperglycemia, and again after 120 min hyperglycemia. Distal (5th finger - wrist......) and proximal (wrist - elbow) sensory nerve conduction showed an insignificant increase as hyperglycemia was induced. During hyperglycemia mean distal sensory conduction decreased from 53.1 m/s to 50.4 m/s (P less than 0.05) and mean proximal sensory conduction decreased from 56.0 m/s to 54.2 m/s (P less than 0...

Monomeric insulins and their experimental and clinical implications.

Science.gov (United States)

Brange, J; Owens, D R; Kang, S; Vølund, A

1990-09-01

Due to the inherent pharmacokinetic properties of available insulins, normoglycemia is rarely, if ever, achieved in insulin-dependent diabetic patients without compromising their quality of life. Subcutaneous insulin absorption is influenced by many factors, among which the associated state of insulin (hexameric) in pharmaceutical formulation may be of importance. This review describes the development of a series of human insulin analogues with reduced tendency to self-association that, because of more rapid absorption, are better suited to meal-related therapy. DNA technology has made it possible to prepare insulins that remain dimeric or even monomeric at high concentration by introducing one or a few amino acid substitutions into human insulin. These analogues were characterized and used for elucidating the mechanisms involved in subcutaneous absorption and were investigated in preliminary clinical studies. Their relative receptor binding and in vitro potency (free-fat cell assay), ranging from 0.05 to 600% relative to human insulin, were strongly correlated (r = 0.97). In vivo, most of the analogues exhibited approximately 100% activity, explainable by a dominating receptor-mediated clearance. This was confirmed by clamp studies in which correlation between receptor binding and clearance was observed. Thus, an analogue with reduced binding and clearance gives higher circulating concentrations, counterbalancing the reduced potency at the cellular level. Absorption studies in pigs revealed a strong inverse correlation (r = 0.96) between the rate of subcutaneous absorption and the mean association state of the insulin analogues. These studies also demonstrated that monomeric insulins were absorbed three times faster than human insulin. In healthy subjects, rates of disappearance from subcutis were two to three times faster for dimeric and monomeric analogues than for human insulin. Concomitantly, a more rapid rise in plasma insulin concentration and an earlier

State of insulin self-association does not affect its absorption from the pulmonary route.

Science.gov (United States)

Hussain, Alamdar; Ahsan, Fakhrul

2005-06-01

This study is designed to compare and contrast the pulmonary absorption profiles of monomeric and hexameric insulin in the presence or absence of ethylene diamine tetraacetic acid (EDTA) or n-tetradecyl-beta-d-maltoside (TDM). The pulmonary absorption of two forms of insulin was studied by monitoring the changes in plasma insulin and glucose levels after intratracheal administration of monomeric or hexameric insulin into anesthetized rodents. EDTA or TDM was added to the formulation in order to evaluate if either of these agents has effects on the rate and extent of pulmonary absorption of monomeric and hexameric insulin. The biochemical changes that may occur after acute administration of TDM-based formulation have also been investigated by estimating lung injury markers in bronchoalveolar lavage fluid. A dose-dependent increase in the plasma insulin and decrease in plasma glucose levels was observed when increasing concentrations of hexameric or monomeric insulin were administered via the pulmonary route. Pulmonary administration of monomeric and hexameric insulin produced comparable absorption profiles in the presence or absence of EDTA or TDM. The bronchoalveolar lavage fluid analysis did not show differences in the levels of injury markers produced in TDM-treated rats and that produced in saline-treated rats, indicating no evidence for adverse effects of TDM in these short-term studies. Overall, in terms of rapidity of action and efficacy to reduce blood sugar, monomeric insulin did not provide advantages over hexameric insulin when administered via the pulmonary route.

Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study

DEFF Research Database (Denmark)

Laakso, M; Zilinskaite, J; Hansen, T

2008-01-01

AIMS/HYPOTHESIS: We examined the phenotype of individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) with regard to insulin release and insulin resistance. METHODS: Non-diabetic offspring (n=874; mean age 40+/-10.4 years; BMI 26.6+/-4.9 kg/m(2)) of type 2 diabetic...

A model of insulin fibrils derived from the x-ray crystal structure of a monomeric insulin (despentapeptide insulin).

Science.gov (United States)

Brange, J; Dodson, G G; Edwards, D J; Holden, P H; Whittingham, J L

1997-04-01

The crystal structure of despentapeptide insulin, a monomeric insulin, has been refined at 1.3 A spacing and subsequently used to predict and model the organization in the insulin fibril. The model makes use of the contacts in the densely packed despentapeptide insulin crystal, and takes into account other experimental evidence, including binding studies with Congo red. The dimensions of this model fibril correspond well with those measured experimentally, and the monomer-monomer contacts within the fibril are in accordance with the known physical chemistry of insulin fibrils. Using this model, it may be possible to predict mutations in insulin that might alleviate problems associated with fibril formation during insulin therapy.

Glucose but not insulin or insulin resistance is associated with memory performance in middle-aged non-diabetic women: a cross sectional study.

Science.gov (United States)

Backeström, Anna; Eriksson, Sture; Nilsson, Lars-Göran; Olsson, Tommy; Rolandsson, Olov

2015-01-01

Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population. We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 ± 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method. A higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = -0.08, 95% CI -0.14; -0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity. This indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.

[Metabolic profile in obese patients with obstructive sleep apnea. A comparison between patients with insulin resistance and with insulin sensitivity].

Science.gov (United States)

Dumitrache-Rujinski, Stefan; Dinu, Ioana; Călcăianu, George; Erhan, Ionela; Cocieru, Alexandru; Zaharia, Dragoş; Toma, Claudia Lucia; Bogdan, Miron Alexandru

2014-01-01

Obstructive sleep apnea syndrome (OSAS) may induce metabolic abnormalities through intermittent hypoxemia and simpathetic activation. It is difficult to demonstrate an independent role of OSAS in the occurrence of metabolic abnormalities, as obesity represents an important risk factor for both OSAS and metabolic abnormalities. to assess the relations between insulin resistance (IR), insulin sensitivity (IS), OSAS severity and nocturnal oxyhaemoglobin levels in obese, nondiabetic patients with daytime sleepiness. We evaluated 99 consecutive, obese, nondiabetic patients (fasting glycemia 5/hour and daytime sleepiness) by an ambulatory six channel cardio-respiratory polygraphy. Hight, weight serum triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) levels were evaluated. Correlations between Apneea Hypopnea Index (AHI), Oxygen Desaturation Index (ODI), average and lowest oxyhaemoglobin saturation (SaO), body mass index (BMI) and insulin resistance or sensitivity were assesed. IR was defined as a TG/ HDL-Cratio > 3, and insulin sensitivity (IS) as a TG/HDL-C ratio obese nondiabetic patients. Preserving insulin sensitivity is more likely when oxyhaemoglobin levels are higher and ODI is lower. Mean lowest nocturnal SaO2 levels seems to be independently involved in the development of insulin resistance as no statistically significant differences were found for BMI between the two groups.

Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons.

Science.gov (United States)

Rodriguez-Rodriguez, Patricia; Sandebring-Matton, Anna; Merino-Serrais, Paula; Parrado-Fernandez, Cristina; Rabano, Alberto; Winblad, Bengt; Ávila, Jesús; Ferrer, Isidre; Cedazo-Minguez, Angel

2017-12-01

Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of 7 days of exercise training on insulin sensitivity and responsiveness in type 2 diabetes mellitus

DEFF Research Database (Denmark)

Kirwan, John P; Solomon, Thomas; Wojta, Daniel M

2009-01-01

sensitivity and responsiveness and 2) short-term exercise training results in improved suppression of hepatic glucose production by insulin. Fourteen obese patients with type 2 diabetes, age 64 +/- 2 yr, underwent a two-stage hyperinsulinemic euglycemic clamp procedure, first stage 40 mU.m(-2).min(-1) insulin......The objectives of this study were to determine whether 1) the improvement in insulin action induced by short-term exercise training in patients with type 2 diabetes is due to an improvement in insulin sensitivity, an improvement in insulin responsiveness, or a combination of improved insulin...... infusion, second stage 1,000 mU.m(-2).min(-1) insulin infusion, together with a [3-(3)H]glucose infusion, before and after 7 days of exercise. The training consisted of 30 min of cycling and 30 min of treadmill walking at approximately 70% of maximal aerobic capacity daily for 7 days. The exercise program...

Total antioxidant and oxidant status in obese children without insulin resistance

OpenAIRE

Ayşegül Doğan Demir; Ufuk Erenberk; İlker Tolga Özgen; Emin Özkaya; Aysel Vahapoğlu Türkmen; M. Ruşen Dündaröz; Özcan Erel

2014-01-01

Objective: Oxidative stress in obese children may lead in adulthood serious conditions such as coronary heart diseases or type 2 diabetes mellitus. In childhood oxidative stress is associated with insulin resistance or extreme obesity. In this study, we aimed to evaluate oxidative stress status in moderately obese children without insulin resistance. Methods: A total of 38 obese children (21 male, 17 female) without insulin resistance, mean aged 9.4±3.8 years) and 51 normal weight children...

Polycystic ovary syndrome (PCOS), insulin resistance and insulin-like growth factors (IGfs)/IGF-binding proteins (IGFBPs).

Science.gov (United States)

Wang, Hsin-Shih; Wang, Tzu-Hao

2003-08-01

Polycystic ovary syndrome (PCOS) is the most frequent androgen disorder of ovarian function. Hyperinsulinemia with insulin resistance is believed to be a key link in the enigmatic generation of the symptoms of PCOS such as anovulatory infertility and hyperandrogenism. Regression of these symptoms may be achieved by reducing the hyperinsulinemia. A growing body of evidence suggests that PCOS patients with hyperinsulinemia have a higher risk to develop diabetes mellitus, hypertension and cardiovascular disease as compared to age-matched women. Although oral contraceptives, progestins, antiandrogens, and ovulation induction agents remain standard therapies, weight loss should also be vigorously encouraged to ameliorate the metabolic consequences of PCOS. In addition, insulin-sensitizing agents are now being shown to be useful alone or combined with standard therapies to alleviate hyperinsulinemia in PCOS. Finally and most importantly, early identification of patients at risk and prompt initiation of therapies, followed by long-term surveillance and management, may promote the patient's long-term health.

Insulin response to oral glucose in healthy, lean young women and patients with polycystic ovary syndrome.

Science.gov (United States)

Kulshreshtha, Bindu; Ganie, Mohammed Ashraf; Praveen, Edavan Pulikkanath; Gupta, Nandita; Lal Khurana, Madan; Seith, Ashu; Dwivedi, Sadanand N; Kumar, Guresh; Ammini, Ariachery C

2008-11-01

Insulin resistance and consequent hyperinsulinemia are common among patients with polycystic ovary syndrome (PCOS). Ethnicity and dietary habits affect insulin levels. There is little published information from India on insulin levels in PCOS patients. Thus the present study aimed to determine the insulin response to oral glucose in women with PCOS and healthy women. In a case-control study design, women with PCOS and lean healthy women without a family history of diabetes mellitus underwent oral glucose tolerance testing. Samples were collected at 0, 1 and 2 h after glucose ingestion. Two hundred and eighty-five women with PCOS and 27 lean healthy young women were enrolled into the study. The mean age of controls was 22.8 +/- 4.5 years (range 15-32 years) and their mean body mass index (BMI) was 19.7 +/- 2.6 kg/m(2). Mean blood glucose at 0, 1 and 2 h was 88.2 +/- 7.2, 115.5 +/- 25.5 and 91.8 +/- 20.5 mg/dl, respectively. Corresponding plasma insulin levels were 5.8 +/- 1.1, 32.7 +/- 26.5 and 14.6 +/- 9.6 mIU/l. Peak insulin levels were seen at 1 h and these came down to less than 40% of the peak value by 2 h. Glucose/insulin ratio at 0, 1 and 2 h was 15.6 +/- 3.1, 7.0 +/- 3.1 and 11.4 +/- 7.0. Homeostasis model assessment of insulin resistance (HOMA-IR) was 1.2 +/- 0.2. The age of the PCOS women ranged from 15 to 40 years (mean 23.4 +/- 6.2 years) and their BMI ranged from 16.4 to 50.4 kg/m(2) (mean 27.7 +/- 6.3 kg/m(2)). One hundred and seventy-six (62%) PCOS patients had normal glucose tolerance (NGT), 39 (14%) had impaired fasting glucose (IFG), 49 (17%) had impaired glucose tolerance (IGT) and 21 (7%) had type 2 diabetes mellitus (T2DM). Insulin response was higher in women with PCOS. Peak insulin was observed at 1 h. The difference between 1-h and 2-h post-glucose insulin decreased with worsening glucose tolerance. Both plasma insulin and BMI showed a rising trend from NGT to IFG to IGT. There was no further increase in either insulin or BMI from IGT to T2DM

Acute effect of insulin on guinea pig airways and its amelioration by pre-treatment with salbutamol

International Nuclear Information System (INIS)

Sharif, M.; Khan, B. T.; Anwar, M. A.

2014-01-01

Objective: To study the magnitude of insulin-mediated airway hyper-reactivity and to explore the protective effects of salbutamol in inhibiting the insulin-induced airway hyper-responsiveness on tracheal smooth muscle of guinea pigs in vitro. Methods: The quasi-experimental study was conducted at the Pharmacology Department of Army Medical College, Rawalpindi, in collaboration with the Centre for Research in Experimental and Applied Medicine from December 2011 to July 2012. It used 18 healthy Dunkin Hartely guinea pigs of either gender. Effects of increasing concentrations of histamine (10-8-10-3M), insulin (10-8-10-3 M) and insulin pre-treated with salbutamol (10-6 M) were observed on isolated tracheal strip of guinea pig in vitro by constructing cumulative concentration response curves. The tracheal smooth muscle contractions were recorded with Transducer on Four Channel Oscillograph. Mean and standard error of mean were calculated. SPSS 16 was used for statistical analysis. Results: Histamine and insulin produced a concentration-dependent reversible contraction of isolated tracheal muscle of guinea pig. The mean of maximum amplitudes of contraction with histamine, insulin and insulin pre-treated with salbutamol were 92. 1.20 mm, 35+-1.13 mm and 14.55+-0.62 mm respectively. Salbutamol shifted the concentration response curve of insulin to the right and downwards. Conclusions: Salbutamol significantly reduced the insulin mediated airway hyper-reactivity in guinea pigs, suggesting that pre-treatment of inhaled insulin with salbutamol may have clinical implication in the amelioration of its potential respiratory adverse effects such as bronchoconstriction. (author)

Effect of long-term high-fat diet intake on peripheral insulin sensibility, blood pressure, and renal function in female rats

Directory of Open Access Journals (Sweden)

Noemi A. V. Roza

2016-02-01

Full Text Available Background: This study determines whether -week high-fat diet (HFD consumption alters insulin sensitivity, kidney function, and blood pressure (BP in female rats when compared with standard rodent diet (ND intake in gender- and age-matched rats. Methods: The present study investigates, in female Wistar HanUnib rats, the effect of long-term high-fat fed group (HFD compared with standard chow on BP by an indirect tail-cuff method using an electrosphygmomanometer, insulin and glucose function, and kidney function by creatinine and lithium clearances. Results: The current study shows glucose tolerance impairment, as demonstrated by increased fasting blood glucose (ND: ±2.8 vs. HFD: 87±3.8 mg/dL associated with reduced insulin secretion (ND: 0.58±0.07 vs. HFD: 0.40±0.03 ng/mL in 8-week female HFD-treated rats. The incremental area under the curve (AUC, ND: 1,4558.0±536.0 vs. HFD: 1,6507.8±661.9, homeostasis model assessment of insulin resistance (HOMA-IR index, and the first-order rate constant for the disappearance of glucose (Kitt were significantly enhanced in 8-week HFD-treated rats compared with age-matched ND group (respectively, P=0.03, P=0.002, and P<0.0001. The current study also shows a significantly higher systolic BP measured in 5 and 8 weeks posttreatment in HFD (5-week HFD-treated: 155.25±10.54 mmHg and 8-week HFD-treated: 165±5.8 mmHg (P=0.0001, when compared to BP values in 5-week ND, 137±4.24 mmHg and 8-week ND, 131.75±5.8 mmHg age-matched group. Otherwise, the glomerular filtration rate and renal sodium handling evaluated by FENa, FEPNa and FEPPNa, were unchanged in both groups. Conclusion: We may conclude that 8-week female HFD-fed rats compared with ND group stimulate harmful effects, such as BP rise and peripheral glucose intolerance. The increased BP occurs through insulin resistance and supposedly decreased vasodilatation response without any change on renal function.

Effect of long-term high-fat diet intake on peripheral insulin sensibility, blood pressure, and renal function in female rats.

Science.gov (United States)

Roza, Noemi A V; Possignolo, Luiz F; Palanch, Adrianne C; Gontijo, José A R

2016-01-01

This study determines whether 8-week high-fat diet (HFD) consumption alters insulin sensitivity, kidney function, and blood pressure (BP) in female rats when compared with standard rodent diet (ND) intake in gender- and age-matched rats. The present study investigates, in female Wistar HanUnib rats, the effect of long-term high-fat fed group (HFD) compared with standard chow on BP by an indirect tail-cuff method using an electrosphygmomanometer, insulin and glucose function, and kidney function by creatinine and lithium clearances. The current study shows glucose tolerance impairment, as demonstrated by increased fasting blood glucose (ND: 78±2.8 vs. HFD: 87±3.8 mg/dL) associated with reduced insulin secretion (ND: 0.58±0.07 vs. HFD: 0.40±0.03 ng/mL) in 8-week female HFD-treated rats. The incremental area under the curve (AUC, ND: 1,4558.0±536.0 vs. HFD: 1,6507.8±661.9), homeostasis model assessment of insulin resistance (HOMA-IR) index, and the first-order rate constant for the disappearance of glucose (Kitt) were significantly enhanced in 8-week HFD-treated rats compared with age-matched ND group (respectively, P=0.03, P=0.002, and P<0.0001). The current study also shows a significantly higher systolic BP measured in 5 and 8 weeks posttreatment in HFD (5-week HFD-treated: 155.25±10.54 mmHg and 8-week HFD-treated: 165±5.8 mmHg) (P=0.0001), when compared to BP values in 5-week ND, 137±4.24 mmHg and 8-week ND, 131.75±5.8 mmHg age-matched group. Otherwise, the glomerular filtration rate and renal sodium handling evaluated by FENa, FEPNa and FEPPNa, were unchanged in both groups. We may conclude that 8-week female HFD-fed rats compared with ND group stimulate harmful effects, such as BP rise and peripheral glucose intolerance. The increased BP occurs through insulin resistance and supposedly decreased vasodilatation response without any change on renal function.

Effects of intraperitoneal insulin versus subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus

Directory of Open Access Journals (Sweden)

M Boering

2016-06-01

Full Text Available Aims Elevated sex hormone-binding globulin (SHBG concentrations have been described in patients with type 1 diabetes mellitus (T1DM, probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII, or subcutaneous (SC, influences SHBG concentrations among T1DM patients. Methods Post hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (±13 years, diabetes duration 23 (±11 years, and hemoglobin A1c (HbA1c 8.7 (±1.1 (72 (±12 mmol/mol. As secondary outcomes, testosterone, 17-β-estradiol, luteinizing hormone (LH, and follicle-stimulating hormone (FSH were analyzed. Results Estimated mean change in SHBG was −10.3nmol/L (95% CI: −17.4, −3.2 during CIPII and 3.7nmol/L (95% CI: −12.0, 4.6 during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was −6.6nmol/L (95% CI: −17.5, 4.3; −12.7nmol/L (95% CI: −25.1, −0.4 for males and −1.7nmol/L (95% CI: −24.6, 21.1 for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; −15.8nmol/L (95% CI: −24.2, −7.5 and −8.3nmol/L (95% CI: −14.4, −2.2, respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2U/L (95% CI: 0.1, 2.2 among males. Conclusions SHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids.

Anti-insulin antibody test

Science.gov (United States)

Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... Normally, there are no antibodies against insulin in your blood. ... different laboratories. Some labs use different measurements or ...

Cerebral insulin, insulin signaling pathway, and brain angiogenesis.

Science.gov (United States)

Zeng, Yi; Zhang, Le; Hu, Zhiping

2016-01-01

Insulin performs unique non-metabolic functions within the brain. Broadly speaking, two major areas of these functions are those related to brain endothelial cells and the blood-brain barrier (BBB) function, and those related to behavioral effects, like cognition in disease states (Alzheimer's disease, AD) and in health. Recent studies showed that both these functions are associated with brain angiogenesis. These findings raise interesting questions such as how they are linked to each other and whether modifying brain angiogenesis by targeting certain insulin signaling pathways could be an effective strategy to treat dementia as in AD, or even to help secure healthy longevity. The two canonical downstream pathways involved in mediating the insulin signaling pathway, the phosphoinositide-3 kinase (PI3K), and mitogen-activated protein kinase (MAPK) cascades, in the brain are supposed to be similar to those in the periphery. PI3K and MAPK pathways play important roles in angiogenesis. Both are involved in stimulating hypoxia inducible factor (HIF) in angiogenesis and could be activated by the insulin signaling pathway. This suggests that PI3K and MAPK pathways might act as cross-talk between the insulin signaling pathway and the angiogenesis pathway in brain. But the cerebral insulin, insulin signaling pathway, and the detailed mechanism in the connection of insulin signaling pathway, brain angiogenesis pathway, and healthy aging or dementias are still mostly not clear and need further studies.

Insulin resistance in obesity can be reliably identified from fasting plasma insulin.

Science.gov (United States)

ter Horst, K W; Gilijamse, P W; Koopman, K E; de Weijer, B A; Brands, M; Kootte, R S; Romijn, J A; Ackermans, M T; Nieuwdorp, M; Soeters, M R; Serlie, M J

2015-12-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), Pobese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

Absence of down-regulation of the insulin receptor by insulin. A possible mechanism of insulin resistance in the rat.

OpenAIRE

Walker, A P; Flint, D J

1983-01-01

Insulin resistance occurs in rat adipocytes during pregnancy and lactation despite increased or normal insulin binding respectively; this suggests that a post-receptor defect exists. The possibility has been examined that, although insulin binding occurs normally, internalization of insulin or its receptor may be impaired in these states. Insulin produced a dose-dependent reduction in the number of insulin receptors on adipocytes from virgin rats maintained in culture medium, probably due to ...

Evidence for insulin resistance in nonobese patients with polycystic ovarian disease.

Science.gov (United States)

Jialal, I; Naiker, P; Reddi, K; Moodley, J; Joubert, S M

1987-05-01

In this study seven normal weight Indian patients with polycystic ovarian disease (PCOD) with no evidence of acanthosis nigricans and 7 age- and weight-matched normal Indian women were studied to determine whether PCOD patients were insulin-resistant. While all 14 women had normal glucose tolerance, the PCOD women had significantly higher mean plasma glucose levels at 30 and 60 min and higher mean incremental glucose areas [incremental areas: PCOD, 9.0 +/- 2.2 (+/- SEM); normal women, 4.0 +/- 0.8 mmol/L; P less than 0.05]. Insulin responses were significantly higher in the PCOD compared to normal women (incremental areas: PCOD, 623.8 +/- 78.3; normal women, 226.2 +/- 30.3 microU/mL; P less than 0.001). Both serum testosterone and androstenedione levels correlated with the insulin areas (r = 0.82; P less than 0.001 and r = 0.86; P less than 0.001, respectively). [125I] Insulin binding to erythrocytes revealed decreased maximum specific binding in the PCOD women (6.9 +/- 0.6%) compared to that in normal women (9.2 +/- 0.7%; P less than 0.02). While Scatchard analysis revealed similar receptor numbers, ID50 values demonstrated decreased receptor affinity in the women with PCOD. In conclusion, in the absence of acanthosis nigricans, nonobese patients with PCOD are insulin resistant, and this insulin resistance correlates with the hyperandrogenism.

Clinical use of the co-formulation of insulin degludec and insulin aspart

DEFF Research Database (Denmark)

Kumar, A; Awata, T; Bain, S C

2016-01-01

(HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice...... a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins....

Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice.

Science.gov (United States)

Musial, Barbara; Fernandez-Twinn, Denise S; Vaughan, Owen R; Ozanne, Susan E; Voshol, Peter; Sferruzzi-Perri, Amanda N; Fowden, Abigail L

2016-04-01

In late pregnancy, maternal insulin resistance occurs to support fetal growth, but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy at day 16 (D16) and near term at D19. Nonpregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by DEXA, tissue insulin signaling protein abundance by Western blotting, glucose tolerance and utilization, and insulin sensitivity using acute insulin administration and hyperinsulinemic-euglycemic clamps with [(3)H]glucose infusion. Whole-body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinemia, insulin-resistant endogenous glucose production, and downregulation of several proteins in hepatic and skeletal muscle insulin signaling pathways relative to NP and D19 values. Insulin resistance was less pronounced at D19, with restoration of NP insulin concentrations, improved hepatic insulin sensitivity, and increased abundance of hepatic insulin signaling proteins. At D16, insulin resistance at whole-body, tissue, and molecular levels will favor fetal glucose acquisition, while improved D19 hepatic insulin sensitivity will conserve glucose for maternal use in anticipation of lactation. Tissue sensitivity to insulin, therefore, alters differentially with proximity to delivery in pregnant mice, with implications for human and other species. © 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.

Insulin sensitivity and carotid intima-media thickness

DEFF Research Database (Denmark)

Kozakova, Michaela; Natali, Andrea; Dekker, Jacqueline

2013-01-01

Despite a wealth of experimental data in animal models, the independent association of insulin resistance with early carotid atherosclerosis in man has not been demonstrated. APPROACH AND RESULTS: We studied a European cohort of 525 men and 655 women (mean age, 44±8 years) free of conditions known...... to affect carotid wall (diabetes mellitus, hypertension, and dyslipidemia). All subjects received an oral glucose tolerance test, a euglycemic hyperinsulinemic clamp (M/I as a measure of insulin sensitivity), and B-mode carotid ultrasound. In 833 participants (380 men), the carotid ultrasound was repeated...

Effects of intranasal insulin on endogenous glucose production in insulin-resistant men.

Science.gov (United States)

Xiao, Changting; Dash, Satya; Stahel, Priska; Lewis, Gary F

2018-03-14

The effects of intranasal insulin on the regulation of endogenous glucose production (EGP) in individuals with insulin resistance were assessed in a single-blind, crossover study. Overweight or obese insulin-resistant men (n = 7; body mass index 35.4 ± 4.4 kg/m 2 , homeostatic model assessment of insulin resistance 5.6 ± 1.6) received intranasal spray of either 40 IU insulin lispro or placebo in 2 randomized visits. Acute systemic spillover of intranasal insulin into the circulation was matched with a 30-minute intravenous infusion of insulin lispro in the nasal placebo arm. EGP was assessed under conditions of a pancreatic clamp with a primed, constant infusion of glucose tracer. Under these experimental conditions, compared with placebo, intranasal administration of insulin did not significantly affect plasma glucose concentrations, EGP or glucose disposal in overweight/obese, insulin-resistant men, in contrast to our previous study, in which an equivalent dose of intranasal insulin significantly suppressed EGP in lean, insulin-sensitive men. Insulin resistance is probably associated with impairment in centrally mediated insulin suppression of EGP. © 2018 John Wiley & Sons Ltd.

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

DEFF Research Database (Denmark)

Højlund, Kurt

2014-01-01

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

Meaning in life: the perspective of long-term care residents.

Science.gov (United States)

Welsh, Darlene; Moore, Sharon L; Getzlaf, Beverley A

2012-07-01

A qualitative approach was used in the exploration of meaning in life for long-term care (LTC) residents. This hermeneutic phenomenological study, as described by van Manen, was conducted using semi-structured interviews with 11 LTC residents from a rural region in Atlantic Canada. Four themes emerged as enhancing meaning in life for the residents in this study: Connectedness, Survival Despite Declining Functional Capacity, Engaging in "Normal" Activities, and Seeking a Place of Refuge. In this article, we describe the emerging themes and the implications for LTC education, practice, and future research. Copyright 2012, SLACK Incorporated.

Dissociation between insulin secretion and DNA synthesis in cultured pancreatic islets

DEFF Research Database (Denmark)

Nielsen, Jens Høiriis

1985-01-01

-Tdr incorporation. However, long-term exposure to IBMX did not result in increased DNA content of the islets. Inhibition of the DNA synthesis by 5 mM hydroxyurea resulted in a marked reduction in DNA content of the islets but no decrease in either insulin release or insulin content when expressed per ng DNA...

Implantable batteryless device for on-demand and pulsatile insulin administration

Science.gov (United States)

Lee, Seung Ho; Lee, Young Bin; Kim, Byung Hwi; Lee, Cheol; Cho, Young Min; Kim, Se-Na; Park, Chun Gwon; Cho, Yong-Chan; Choy, Young Bin

2017-04-01

Many implantable systems have been designed for long-term, pulsatile delivery of insulin, but the lifetime of these devices is limited by the need for battery replacement and consequent replacement surgery. Here we propose a batteryless, fully implantable insulin pump that can be actuated by a magnetic field. The pump is prepared by simple-assembly of magnets and constituent units and comprises a drug reservoir and actuator equipped with a plunger and barrel, each assembled with a magnet. The plunger moves to noninvasively infuse insulin only when a magnetic field is applied on the exterior surface of the body. Here we show that the dose is easily controlled by varying the number of magnet applications. Also, pump implantation in diabetic rats results in profiles of insulin concentration and decreased blood glucose levels similar to those observed in rats treated with conventional subcutaneous insulin injections.

[New insulin types in type 1 diabetes mellitus].

Science.gov (United States)

Mesa, Jordi

2015-07-20

Since its discovery almost a century ago, insulin remains the mainstay of treatment of patients with type 1 diabetes mellitus. Although progress in the synthesis of new formulations has been remarkable, the physiological profile of insulin is still different from that observed with preparations available nowadays. In the last decade, the introduction into clinical practice of insulin analogues has allowed significantly improvement in glycemic control and has facilitated the spread of basal/bolus patterns, the most physiological ones until now. Despite the benefits of basal analogues, glycemia often varies considerably when used as a single daily injection and this is why new molecules have been further investigated. Improvement has been achieved especially in terms of duration and rate of hypoglycemia, the main limiting factor of intensive therapy. This article reviews the available data concerning the new basal insulin analogues, degludec, pegylated lispro and glargine U300, and new formulations currently under development. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of Lung Cancer.

Science.gov (United States)

Argirion, Ilona; Weinstein, Stephanie J; Männistö, Satu; Albanes, Demetrius; Mondul, Alison M

2017-10-01

Background: Although insulin may increase the risk of some cancers, few studies have examined fasting serum insulin and lung cancer risk. Methods: We examined serum insulin, glucose, and indices of insulin resistance [insulin:glucose molar ratio and homeostasis model assessment of insulin resistance (HOMA-IR)] and lung cancer risk using a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. A total of 196 cases and 395 subcohort members were included. Insulin and glucose were measured in fasting serum collected 5 to 12 years before diagnosis. Cox proportional hazards models were utilized to estimate the relative risk of lung cancer. Results: The average time between blood collection and lung cancer was 9.6 years. Fasting serum insulin levels were 8.7% higher in subcohort members than cases. After multivariable adjustment, men in the fourth quartile of insulin had a significantly higher risk of lung cancer than those in the first quartile [HR = 2.10; 95% confidence interval (CI), 1.12-3.94]. A similar relationship was seen with HOMA-IR (HR = 1.83; 95% CI, 0.99-3.38). Risk was not strongly associated with glucose or the insulin:glucose molar ratio ( P trend = 0.55 and P trend = 0.27, respectively). Conclusions: Higher fasting serum insulin concentrations, as well as the presence of insulin resistance, appear to be associated with an elevated risk of lung cancer development. Impact: Although insulin is hypothesized to increase risk of some cancers, insulin and lung cancer remain understudied. Higher insulin levels and insulin resistance were associated with increased lung cancer risk. Although smoking cessation is the best method of lung cancer prevention, other lifestyle changes that affect insulin concentrations and sensitivity may reduce lung cancer risk. Cancer Epidemiol Biomarkers Prev; 26(10); 1519-24. ©2017 AACR . ©2017 American Association for Cancer Research.

Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects

DEFF Research Database (Denmark)

Kofoed, Klaus F; Hove, Jens D; Freiberg, Jacob

2002-01-01

The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure...... rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion...... = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole...

Differential effects of insulin injections and insulin infusions on levels ...

African Journals Online (AJOL)

Studies have shown that while injections of insulin cause an increase in fat mass, infusions of insulin increase fat mass. The aim of this paper was to test the hypothesis that if an increase in glycogen is an indicator of an impending increase in adipose mass, then insulin infusions should not increase glycogen, while insulin ...

Insulin delivery route for the artificial pancreas: subcutaneous, intraperitoneal, or intravenous? Pros and cons.

Science.gov (United States)

Renard, Eric

2008-07-01

Insulin delivery is a crucial component of a closed-loop system aiming at the development of an artificial pancreas. The intravenous route, which has been used in the bedside artificial pancreas model for 30 years, has clear advantages in terms of pharmacokinetics and pharmacodynamics, but cannot be used in any ambulatory system so far. Subcutaneous (SC) insulin infusion benefits from the broad expansion of insulin pump therapy that promoted the availability of constantly improving technology and fast-acting insulin analog use. However, persistent delays of insulin absorption and action, variability and shortterm stability of insulin infusion from SC-inserted catheters generate effectiveness and safety issues in view of an ambulatory, automated, glucose-controlled, artificial beta cell. Intraperitoneal insulin delivery, although still marginally used in diabetes care, may offer an interesting alternative because of its more-physiological plasma insulin profiles and sustained stability and reliability of insulin delivery.

Economic benefits of improved insulin stability in insulin pumps.

Science.gov (United States)

Weiss, Richard C; van Amerongen, Derek; Bazalo, Gary; Aagren, Mark; Bouchard, Jonathan R

2011-05-01

Insulin pump users discard unused medication and infusion sets according to labeling and manufacturer's instructions. The stability labeling for insulin aspart (rDNA origin] (Novolog) was increased from two days to six. The associated savings was modeled from the perspective of a hypothetical one-million member health plan and the total United States population. The discarded insulin volume and the number of infusion sets used under a two-day stability scenario versus six were modeled. A mix of insulin pumps of various reservoir capacities with a range of daily insulin dosages was used. Average daily insulin dose was 65 units ranging from 10 to 150 units. Costs of discarded insulin aspart [rDNA origin] were calculated using WAC (Average Wholesale Price minus 16.67%). The cost of pump supplies was computed for the two-day scenario assuming a complete infusion set change, including reservoirs, every two days. Under the six-day scenario complete infusion sets were discarded every six days while cannulas at the insertion site were changed midway between complete changes. AWP of least expensive supplies was used to compute their costs. For the hypothetical health plan (1,182 pump users) the annual reduction in discarded insulin volume between scenarios was 19.8 million units. The corresponding cost reduction for the plan due to drug and supply savings was $3.4 million. From the U.S. population perspective, savings of over $1 billion were estimated. Using insulin that is stable for six days in pump reservoirs can yield substantial savings to health plans and other payers, including patients.

Insulin analogues in type 1 diabetes mellitus: getting better all the time.

Science.gov (United States)

Mathieu, Chantal; Gillard, Pieter; Benhalima, Katrien

2017-07-01

The treatment of type 1 diabetes mellitus consists of external replacement of the functions of β cells in an attempt to achieve blood levels of glucose as close to the normal range as possible. This approach means that glucose sensing needs to be replaced and levels of insulin need to mimic physiological insulin-action profiles, including basal coverage and changes around meals. Training and educating patients are crucial for the achievement of good glycaemic control, but having insulin preparations with action profiles that provide stable basal insulin coverage and appropriate mealtime insulin peaks helps people with type 1 diabetes mellitus to live active lives without sacrificing tight glycaemic control. Insulin analogues enable patients to achieve this goal, as some have fast action profiles, and some have very slow action profiles, which gives people with type 1 diabetes mellitus the tools to achieve dynamic insulin-action profiles that enable tight glycaemic control with a risk of hypoglycaemia that is lower than that with human short-acting and long-acting insulins. This Review discusses the established and novel insulin analogues that are used to treat patients with type 1 diabetes mellitus and provides insights into the future development of insulin analogues.

Influence of Unweighting on Insulin Signal Transduction in Muscle

Science.gov (United States)

Tischler, Marc E.

2002-01-01

Unweighting of the juvenile soleus muscle is characterized by an increased binding capacity for insulin relative to muscle mass due to sparing of the receptors during atrophy. Although carbohydrate metabolism and protein degradation in the unweighted muscle develop increased sensitivity to insulin in vivo, protein synthesis in vivo and system A amino acid transport in vitro do not appear to develop such an enhanced response. The long-term goal is to identify the precise nature of this apparent resistance in the insulin signal transduction pathway and to consider how reduced weight-bearing may elicit this effect, by evaluating specific components of the insulin signalling pathway. Because the insulin-signalling pathway has components in common with the signal transduction pathway for insulin-like growth factor (IGF-1) and potentially other growth factors, the study could have important implications in the role of weight-bearing function on muscle growth and development. Since the insulin signalling pathway diverges following activation of insulin receptor tyrosine kinase, the immediate specific aims will be to study the receptor tyrosine kinase (IRTK) and those branches, which lead to phosphorylation of insulin receptor substrate-1 (IRS-1) and of Shc protein. To achieve these broader objectives, we will test in situ, by intramuscular injection, the responses of glucose transport, system A amino acid transport and protein synthesis to insulin analogues for which the receptor has either a weaker or much stronger binding affinity compared to insulin. Studies will include: (1) estimation of the ED(sub 50) for each analogue for these three processes; (2) the effect of duration (one to four days) of unweighting on the response of each process to all analogues tested; (3) the effect of unweighting and the analogues on IRTK activity; and (4) the comparative effects of unweighting and analogue binding on the tyrosine phosphorylation of IRTK, IRS-1, and Shc protein.

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

Science.gov (United States)

Højlund, Kurt

2014-07-01

Type 2 diabetes, obesity and polycystic ovary syndrome (PCOS) are common metabolic disorders which are observed with increasing prevalences, and which are caused by a complex interplay between genetic and environmental factors, including increased calorie intake and physical inactivity. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes and cardiovascular disease. In several studies, we have investigated insulin action on glucose and lipid metabolism, and at the molecular level, insulin signaling to glucose transport and glycogen synthesis in skeletal muscle from healthy individuals and in obesity, PCOS and type 2 diabetes. Moreover, we have described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance. Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin action on glucose uptake and glycogen synthesis is impaired. This suggests that the defects in glucose and lipid oxidation in the common metabolic disorders are secondary to other factors. In young women with PCOS, the degree of insulin resistance was similar to that seen in middle-aged patients with type 2 diabetes. This supports the hypothesis of an unique pathogenesis of insulin resistance in PCOS. Insulin in physiological concentrations stimulates glucose uptake in human skeletal

Effectiveness of insulin glargine in type 2 diabetes mellitus patients failing glycaemic control with premixed insulin: Adriatic countries data meta-analysis.

Science.gov (United States)

Cigrovski Berkovic, Maja; Petrovski, Goran; Grulovic, Natasa

2016-10-01

Type 2 diabetes mellitus (T2DM) is a progressive disease, often requiring exogenous insulin therapy and treatment intensification. Despite new therapies, most patients do not reach the recommended HbA1c targets, among them a significant proportion of patients on premixed insulins. The aim was to summarize published data in Adriatic countries on effectiveness of insulin glargine based therapy in type 2 diabetic patients suboptimally controlled on premix insulin. A meta-analysis was carried out in major medical databases up to April 2014, focusing on Adriatic region. We searched observational studies with duration of at least 6 months, evaluating effectiveness and safety of insulin glargine (IGlar), in combination with OAD or bolus insulin in patients with T2 failing premixed insulin therapy. Outcomes included values of HbA1c, fasting blood glucose and two hours post-prandial glucose concentration as well as changes in body mass index after at least 6 months of study duration. Three prospective, observational, multicentric trials (698 patients in total) were included. The basal bolus regimen with glargine significantly reduced HbA1c (Mean Difference, MD=2.27, CI [1.76, 2.78]), fasting glucose (MD=5.15, CI [4.86, 5.44]) and 2-hours postprandial glucose concentration (MD=6.94, CI [6.53, 7.34]). No significant changes were found in BMI after switching from premixes to IGlar based treatment. Insulin glargine based therapy following premix failure is efficacious and safe option of type 2 diabetes treatment intensification.

Insulin secretion and incretin hormones after oral glucose in non-obese subjects with impaired glucose tolerance

DEFF Research Database (Denmark)

Rask, E; Olsson, T; Söderberg, S

2004-01-01

of glucose, insulin, C-peptide, GLP-1, and GIP. Insulin secretion (TIS) and insulin sensitivity (OGIS) were assessed using models describing the relationship between glucose, insulin and C-peptide data. These models allowed estimation also of the hepatic extraction of insulin. The age (54.2 +/- 9.7 [mean......Subjects with impaired glucose tolerance (IGT) are usually overweight and exhibit insulin resistance with a defective compensation of insulin secretion. In this study, we sought to establish the interrelation between insulin secretion and insulin sensitivity after oral glucose in non-obese subjects...... over the whole 180-minute period was higher in IGT (26.2 +/- 2.4 v 20.0 +/- 2.0 nmol/L; P =.035). Hepatic insulin extraction correlated linearly with OGIS (r = 0.71; P

Pregestational diabetes with extreme insulin resistance: use of U-500 insulin in pregnancy.

Science.gov (United States)

Zuckerwise, Lisa C; Werner, Erika F; Pettker, Christian M; McMahon-Brown, Erin K; Thung, Stephen F; Han, Christina S

2012-08-01

Increased insulin requirements in pregnancy can hinder attainment of glycemic control in diabetic patients. U-500 insulin is a concentrated form of regular insulin that can be a valuable tool in the treatment of patients with severe insulin resistance. A 24-year-old woman with pregestational diabetes mellitus experienced increasing insulin requirements during pregnancy, peaking at 650 units daily. The frequent, large-volume injections of standard-concentration insulin were poorly tolerated by the patient and resulted in nonadherence. She subsequently achieved glycemic control on thrice-daily U-500 insulin. Pregnancy exacerbates insulin resistance in diabetic patients, and these patients may require high doses of insulin. U-500 insulin is an effective alternative for patients with severe insulin resistance and should be considered for pregnant women with difficulty achieving glycemic control.

Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans

DEFF Research Database (Denmark)

Stefan, Norbert; Vozarova, Barbora; Funahashi, Tohru

2002-01-01

(insulin-stimulated glucose disposal, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) were measured in 55 Pima Indians (47 men and 8 women, aged 31 +/- 8 years, body fat 29 +/- 8% [mean +/- SD]; 50 with normal glucose tolerance, 3 with impaired glucose tolerance, and 2......Adiponectin, the most abundant adipose-specific protein, has been found to be negatively associated with degree of adiposity and positively associated with insulin sensitivity in Pima Indians and other populations. Moreover, adiponectin administration to rodents has been shown to increase insulin...

Development of a bioassay system for investigating insulin resistance factors of pregnancy

International Nuclear Information System (INIS)

Hausman, D.B.; Singh, R.; Martin, R.J.

1986-01-01

To determine if late-term pregnant serum and/or placenta could induce insulin resistance in normal adipose cells, the authors have developed an insulin sensitive bioassay system. Cells isolated from epididymal fat pads of 250-275 g Sprague Dawley rats are preincubated for 3 hours at 37 0 in media 199 and serum or placental extract. The cells are washed free of serum and tested for metabolic activity in a 2 hour incubation which measures the conversion of U- 14 C-glucose to 14 CO 2 and to 14 C-triglyceride fatty acids under basal and insulin stimulated conditions. Maximal insulin responsiveness (350-450% basal for CO 2 and 1400-1700% basal for fatty acids) is achieved using Worthington Type II collagenase and a 45-60 minute digestion period for cell isolations and Krebs-Ringer bicarbonate buffer containing 0.5 mM glucose, 2% Armour bovine serum albumin (CRG-7), 1000 μU/ml insulin and 110,000 to 120,000 cells in the 2 hour incubations. Using this bioasssay system the authors have found that insulin responsiveness, in terms of glucose conversion to fatty acids, is unchanged when cells are preincubated with 5% control pig serum but reduced following preincubation with late pregnant (110 day) pig serum. In future experiments the authors hope to further characterize the factor(s) in pregnant serum responsible for inducing this metabolic effect

Adiponectin inhibits insulin function in primary trophoblasts by PPARα-mediated ceramide synthesis.

Science.gov (United States)

Aye, Irving L M H; Gao, Xiaoli; Weintraub, Susan T; Jansson, Thomas; Powell, Theresa L

2014-04-01

Maternal adiponectin (ADN) levels are inversely correlated with birth weight, and ADN infusion in pregnant mice down-regulates placental nutrient transporters and decreases fetal growth. In contrast to the insulin-sensitizing effects in adipose tissue and muscle, ADN inhibits insulin signaling in the placenta. However, the molecular mechanisms involved are unknown. We hypothesized that ADN inhibits insulin signaling and insulin-stimulated amino acid transport in primary human trophoblasts by peroxisome proliferator-activated receptor-α (PPARα)-mediated ceramide synthesis. Primary human term trophoblast cells were treated with ADN and/or insulin. ADN increased the phosphorylation of p38 MAPK and PPARα. ADN inhibited insulin signaling and insulin-stimulated amino acid transport. This effect was dependent on PPARα, because activation of PPARα with an agonist (GW7647) inhibited insulin signaling and function, whereas PPARα-small interfering RNA reversed the effects of ADN on the insulin response. ADN increased ceramide synthase expression and stimulated ceramide production. C2-ceramide inhibited insulin signaling and function, whereas inhibition of ceramide synthase (with Fumonisin B1) reversed the effects of ADN on insulin signaling and amino acid transport. These findings are consistent with the model that maternal ADN limits fetal growth mediated by activation of placental PPARα and ceramide synthesis, which inhibits placental insulin signaling and amino acid transport, resulting in reduced fetal nutrient availability.

Effects of insulin on the survival of irradiated chinese hamster lung cells

Energy Technology Data Exchange (ETDEWEB)

Lin, P S; Kwock, L; Hefter, K; Wallach, D F.H.; Brotman, R [Tufts-New England Medical Center, Boston, Mass. (USA)

1977-01-01

Insulin treatment (10/sup -7/-10/sup -9/ M) before ..gamma.. irradiation (50 to 500 rads) increases the long term survival of Chinese hamster lung cells (DON). Our data indicates that the radioprotective effect of insulin is not due to a modulation of cyclic-adenosine-3',5'-monophosphate levels within these cells. The results suggest that the radiosensitive plasma membrane component postulated to be involved in the interphase death of thymocytes and protected by insulin may have a counterpart in DON cells.

Long-term prophylactic insulin treatment can prevent spontaneous diabetes and thyroiditis development in the diabetes-prone bio-breeding rat, while short-term treatment is ineffective

NARCIS (Netherlands)

Visser, J.; Klatter, F; Vis, L; Groen, Harry; Strubbe, J.H.; Rozing, Nico

Objective: Prophylactic insulin treatment has been demonstrated to reduce diabetes development in the diabetes-prone bio-breeding (DP-BB) rat. These prophylactic insulin treatments were given from 50 to 150 days of age. However, several data indicate that the diabetogenic process in DP-BB rats

Alternative translation initiation of Caveolin-2 desensitizes insulin signaling through dephosphorylation of insulin receptor by PTP1B and causes insulin resistance.

Science.gov (United States)

Kwon, Hayeong; Jang, Donghwan; Choi, Moonjeong; Lee, Jaewoong; Jeong, Kyuho; Pak, Yunbae

2018-06-01

Insulin resistance, defined as attenuated sensitivity responding to insulin, impairs insulin action. Direct causes and molecular mechanisms of insulin resistance have thus far remained elusive. Here we show that alternative translation initiation (ATI) of Caveolin-2 (Cav-2) regulates insulin sensitivity. Cav-2β isoform yielded by ATI desensitizes insulin receptor (IR) via dephosphorylation by protein-tyrosine phosphatase 1B (PTP1B), and subsequent endocytosis and lysosomal degradation of IR, causing insulin resistance. Blockage of Cav-2 ATI protects against insulin resistance by preventing Cav-2β-PTP1B-directed IR desensitization, thereby normalizing insulin sensitivity and glucose uptake. Our findings show that Cav-2β is a negative regulator of IR signaling, and identify a mechanism causing insulin resistance through control of insulin sensitivity via Cav-2 ATI. Copyright © 2018 Elsevier B.V. All rights reserved.

Improving long-term care provision: towards demand-based care by means of modularity

Directory of Open Access Journals (Sweden)

Meijboom Bert

2010-09-01

Full Text Available Abstract Background As in most fields of health care, societal and political changes encourage suppliers of long-term care to put their clients at the center of care and service provision and become more responsive towards client needs and requirements. However, the diverse, multiple and dynamic nature of demand for long-term care complicates the movement towards demand-based care provision. This paper aims to advance long-term care practice and, to that end, examines the application of modularity. This concept is recognized in a wide range of product and service settings for its ability to design demand-based products and processes. Methods Starting from the basic dimensions of modularity, we use qualitative research to explore the use and application of modularity principles in the current working practices and processes of four organizations in the field of long-term care for the elderly. In-depth semi-structured interviews were conducted with 38 key informants and triangulated with document research and observation. Data was analyzed thematically by means of coding and subsequent exploration of patterns. Data analysis was facilitated by qualitative analysis software. Results Our data suggest that a modular setup of supply is employed in the arrangement of care and service supply and assists providers of long-term care in providing their clients with choice options and variation. In addition, modularization of the needs assessment and package specification process allows the case organizations to manage client involvement but still provide customized packages of care and services. Conclusion The adequate setup of an organization's supply and its specification phase activities are indispensible for long-term care providers who aim to do better in terms of quality and efficiency. Moreover, long-term care providers could benefit from joint provision of care and services by means of modular working teams. Based upon our findings, we are able to

Improving long-term care provision: towards demand-based care by means of modularity

Science.gov (United States)

2010-01-01

Background As in most fields of health care, societal and political changes encourage suppliers of long-term care to put their clients at the center of care and service provision and become more responsive towards client needs and requirements. However, the diverse, multiple and dynamic nature of demand for long-term care complicates the movement towards demand-based care provision. This paper aims to advance long-term care practice and, to that end, examines the application of modularity. This concept is recognized in a wide range of product and service settings for its ability to design demand-based products and processes. Methods Starting from the basic dimensions of modularity, we use qualitative research to explore the use and application of modularity principles in the current working practices and processes of four organizations in the field of long-term care for the elderly. In-depth semi-structured interviews were conducted with 38 key informants and triangulated with document research and observation. Data was analyzed thematically by means of coding and subsequent exploration of patterns. Data analysis was facilitated by qualitative analysis software. Results Our data suggest that a modular setup of supply is employed in the arrangement of care and service supply and assists providers of long-term care in providing their clients with choice options and variation. In addition, modularization of the needs assessment and package specification process allows the case organizations to manage client involvement but still provide customized packages of care and services. Conclusion The adequate setup of an organization's supply and its specification phase activities are indispensible for long-term care providers who aim to do better in terms of quality and efficiency. Moreover, long-term care providers could benefit from joint provision of care and services by means of modular working teams. Based upon our findings, we are able to elaborate on how to further

Analog insulin detemir for patients with type 1 and type 2 diabetes: a review

Directory of Open Access Journals (Sweden)

Gregory E Peterson

2009-05-01

Full Text Available Gregory E PetersonDepartment of Internal Medicine, Des Moines University, USAObjective: To review insulin detemir for clinical use to better manage patients with type 1 and type 2 diabetes.Methods: A MEDLINE search, in English, from June 30, 2006 to December 1, 2008, using the terms “insulin analogs,” “insulin detemir” and “long-acting insulin analog.”Results: Insulin detemir improves glycemic control, based on HbA1C reduction and fasting glucose levels, without increasing the risk of hypoglycemia and weight gain. Insulin detemir has lower glycemic variability, with less intra-subject variability in blood glucose levels in patients with type 1 and type 2 diabetes, without increasing the risk of hypoglycemia. When added to oral anti-diabetes agents (OADs in type 2 diabetes, insulin detemir demonstrates superiority to other basal insulin options.Conclusion: Insulin detemir appears to provide better glycemic control with a lower risk of hypoglycemia and less weight gain in the treatment of patients with type 1 and type 2 diabetes.Keywords: type 1 diabetes, type 2 diabetes, insulin analogs, insulin detemir

Design and clinical pilot testing of the model-based dynamic insulin sensitivity and secretion test (DISST).

Science.gov (United States)

Lotz, Thomas F; Chase, J Geoffrey; McAuley, Kirsten A; Shaw, Geoffrey M; Docherty, Paul D; Berkeley, Juliet E; Williams, Sheila M; Hann, Christopher E; Mann, Jim I

2010-11-01

Insulin resistance is a significant risk factor in the pathogenesis of type 2 diabetes. This article presents pilot study results of the dynamic insulin sensitivity and secretion test (DISST), a high-resolution, low-intensity test to diagnose insulin sensitivity (IS) and characterize pancreatic insulin secretion in response to a (small) glucose challenge. This pilot study examines the effect of glucose and insulin dose on the DISST, and tests its repeatability. DISST tests were performed on 16 subjects randomly allocated to low (5 g glucose, 0.5 U insulin), medium (10 g glucose, 1 U insulin) and high dose (20 g glucose, 2 U insulin) protocols. Two or three tests were performed on each subject a few days apart. Average variability in IS between low and medium dose was 10.3% (p=.50) and between medium and high dose 6.0% (p=.87). Geometric mean variability between tests was 6.0% (multiplicative standard deviation (MSD) 4.9%). Geometric mean variability in first phase endogenous insulin response was 6.8% (MSD 2.2%). Results were most consistent in subjects with low IS. These findings suggest that DISST may be an easily performed dynamic test to quantify IS with high resolution, especially among those with reduced IS. © 2010 Diabetes Technology Society.

Vitamin D and insulin resistance in postmenopausal Indian women

Directory of Open Access Journals (Sweden)

Niti Agarwal

2014-01-01

Full Text Available Purpose: The purpose of this study is to investigate the association of the serum 25-hydroxyvitamin D (25-OHD level with markers of insulin resistance (IR in postmenopausal Indian women. Materials and Methods: This was a cross-sectional study, conducted at a Tertiary Care Hospital in New Delhi, India. Seventy one postmenopausal women (mean age 56.3 ± 7.6 years were enrolled. Exclusion criteria were known or newly detected diabetics, subjects with chronic renal failure, chronic liver disease or any other chronic inflammatory condition, chronic smokers and chronic alcoholics. Serum calcium (and albumin for calculating corrected calcium, phosphorus, alkaline phosphatase and 25-OHD were measured as parameters of calcium homeostasis. Fasting blood glucose (FBG, systolic and diastolic blood pressures, body mass index (BMI, fasting serum insulin, calculated glucose insulin ratio (GIR, and homeostatic model assessment of insulin resistance (HOMA-IR were studied as parameters of IR. Data was then analyzed for statistical significance. Results: The mean serum 25-OHD level was 12.73 ± 7.63 ng/ml. The mean BMI was 27.78 ± 5.37 kg/m 2 . The mean calculated GIR was 13.14 ± 9.39 and HOMA-IR was 2.31 ± 1.70. Serum 25-OHD was inversely correlated with BMI (correlation coefficient −0.234, P value 0.050 and with HOMA-IR (correlation coefficient −0.237, P value 0.047. However, when 25-OHD was adjusted for BMI the correlation between 25-OHD and HOMA-IR lost its significance. No correlation was found between serum 25-OHD and any other parameters of IR studied. Conclusions: There is a significant negative linear correlation between 25-OHD and BMI. The significant negative linear correlation between 25-OHD and HOMA-IR was confounded by BMI. There is no correlation between 25-OHD and parameters of IR.

Conversion from insulin glargine U-100 to insulin glargine U-300 or insulin degludec and the impact on dosage requirements.

Science.gov (United States)

Pearson, Scott M; Trujillo, Jennifer M

2018-04-01

We wanted to determine whether basal insulin requirements change when patients transition from insulin glargine U-100 (Gla-100) to insulin glargine U-300 (Gla-300) or insulin degludec. This study involved subjects seen in the University of Colorado Health Endocrine Clinic who were transitioned from Gla-100 to either Gla-300 ( n = 95) or insulin degludec ( n = 39). The primary outcome was the difference between baseline Gla-100 dose and dose of Gla-300 or insulin degludec prescribed after first follow-up visit within 1-12 months. Secondary outcomes included changes in glycemic control and empiric dose conversion from Gla-100 to Gla-300 or insulin degludec on the day of transition. Wilcoxon rank sum tests evaluated changes in insulin doses, and paired t tests assessed changes in glycemic control using GraphPad statistical software. Median daily basal insulin dose increased for individuals transitioned from Gla-100 to Gla-300 from 30 [19-60 interquartile range (IQR)] units at baseline to 34.5 (19-70 IQR) units after follow up ( p = 0.01). For patients transitioned to insulin degludec, dose changes from baseline to follow up were not significantly different ( p = 0.56). At the time of transition, the prescribed dose of Gla-300 or insulin degludec did not significantly differ from the previous dose of Gla-100 ( p = 0.73 and 0.28, respectively), indicating that empiric dose adjustments were not routinely prescribed. Patients who transitioned from Gla-100 to Gla-300 had increased basal insulin requirements between visits, while basal insulin requirements for those transitioned from Gla-100 to insulin degludec were not significantly different.

Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes

Science.gov (United States)

Oh, Da Hee; Kim, Jung Yeon; Lee, Bong Gn; You, Jeong Soon; Chang, Kyung Ja; Chung, Hyunju; Yoo, Myung Chul; Yang, Hyung-In; Kang, Ja-Heon; Hwang, Yoo Chul; Ahn, Kue Jeong; Chung, Ho-Yeon

2012-01-01

This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve β-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients. PMID:23114424

(B1-/sup 125/I-desaminotyrosine)-insulin - A novel homogeneous insulin tracer

Energy Technology Data Exchange (ETDEWEB)

Bahrami, S; Zahn, H; Brandenburg, D [Deutsches Wollforschungsinstitut, Aachen (Germany F.R.); Machulla, H -J; Dutschka, K [Institut fuer Medizinische Strahlenphysik und Strahlenbiologie des Universitaetsklinikum, Essen (Germany F.R.)

1980-10-28

(B1-/sup 125/I-desaminotyrosine)-insulin (/sup 125/I-MII) was prepared with high specific activities (420 Ci/mmole) by exchanging B1-phenylalanine for /sup 125/I-p-hydroxyphenyl-propionic acid N-hydroxysuccinimide ester (Bolton-Hunter reagent). Overall radiochemical yields were about 8%. Analytical quality control and purification were performed by means of radio high pressure liquid chromatography. The radiochemical purity of /sup 125/I-MII was >99%, and the immunoprecipitability was 97%.

Parity Increases Insulin Requirements in Pregnant Women With Type 1 Diabetes.

Science.gov (United States)

Skajaa, Gitte Ø; Fuglsang, Jens; Kampmann, Ulla; Ovesen, Per G

2018-06-01

Tight glycemic control throughout pregnancy in women with type 1 diabetes is crucial, and knowledge about which factors that affect insulin sensitivity could improve the outcome for both mother and offspring. To evaluate insulin requirements in women with type 1 diabetes during pregnancy and test whether parity affects insulin requirements. Observational cohort study consisting of women with type 1 diabetes who gave birth at Aarhus University Hospital, Denmark, from 2004 to 2014. Daily insulin requirement (the hypothesis that parity could affect insulin resistance was formulated before data collection). A total of 380 women with a total of 536 pregnancies were included in the study. Mean age was 31.1 years, and prepregnancy hemoglobin A1c was 60 mmol/mol. Parity was as follows: P0, 43%; P1, 40%; P2, 14%; and P3+4, 3%. Insulin requirements from weeks 11 to 16 decreased significantly by 4% (P = 0.0004) and rose from week 19 to delivery with a peak of 70% (P insulin requirements increased significantly with parity. The unadjusted differences between P0 and P1, P2, and P3+4 were 9% (P insulin requirements from week to week in pregnancy and indicate that insulin requirements increase with parity. This suggests that the patient's parity probably should be considered in choosing insulin dosages for pregnant women with type 1 diabetes.

Heterogeneous response of isolated adult rat heart cells to insulin

International Nuclear Information System (INIS)

Haworth, R.A.; Hunter, D.R.; Berkoff, H.A.

1984-01-01

3-O-Methylglucose uptake by Ca2+-resistant adult rat heart cells in suspension was measured, free of artifactual inhibitor-insensitive uptake, and with an accuracy of +/- 1.9% pellet water. (Ca2+-resistant cells are cells which retain their original rod-shaped morphology in the presence of physiological levels of Ca2+.) High levels of insulin (10(-6) M) stimulated the rate of 3-O-methylglucose uptake approximately 10-fold. In the presence of low levels of insulin (3 X 10(-11) M, 10(-10) M) uptake was biphasic; it could not be described by a single exponential function within experimental error, but required the sum of two exponentials. Deviation from a single exponential function was not so great with high levels of insulin (10(-6) M) or no insulin. Cell sugar uptake was also investigated using autoradiography of cells which had accumulated [2-14C]deoxyglucose under similar conditions. This showed considerable heterogeneity of 2-deoxyglucose uptake by cells treated with low levels of insulin, but significantly less heterogeneity of 2-deoxyglucose uptake by cells treated with high levels of insulin. It is concluded that the deviation of 3-O-methylglucose uptake from a single exponential observed at low insulin levels can be accounted for in terms of a heterogeneous response of cells to insulin

Prediction of the association state of insulin using spectral parameters.

Science.gov (United States)

Uversky, Vladimir N; Garriques, Liza Nielsen; Millett, Ian S; Frokjaer, Sven; Brange, Jens; Doniach, Sebastian; Fink, Anthony L

2003-04-01

Human insulin exists in different association states, from monomer to hexamer, depending on the conditions. In the presence of zinc the "normal" state is a hexamer. The structural properties of 20 variants of human insulin were studied by near-UV circular dichroism, fluorescence spectroscopy, and small-angle X-ray scattering (SAXS). The mutants showed different degrees of association (monomer, dimers, tetramers, and hexamers) at neutral pH. A correlation was shown between the accessibility of tyrosines to acrylamide quenching and the degree of association of the insulin mutants. The near-UV CD spectra of the insulins were affected by protein association and by mutation-induced structural perturbations. However, the shape and intensity of difference CD spectra, obtained by subtraction of the spectra measured in 20% acetic acid (where all insulin species were monomeric) from the corresponding spectra measured at neutral pH, correlate well with the degree of insulin association. In fact, the near-UV CD difference spectra for monomeric, dimeric, tetrameric, and hexameric insulin are very distinctive, both in terms of intensity and shape. The results show that the spectral properties of the insulins reflect their state of association, and can be used to predict their oligomeric state. Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:847-858, 2003

Update on insulin treatment for dogs and cats: insulin dosing pens and more

Directory of Open Access Journals (Sweden)

Thompson A

2015-04-01

Full Text Available Ann Thompson,1 Patty Lathan,2 Linda Fleeman3 1School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia; 2College of Veterinary Medicine Mississippi State University, Starkville, MS, USA; 3Animal Diabetes Australia, Melbourne, VIC, Australia Abstract: Insulin therapy is still the primary therapy for all diabetic dogs and cats. Several insulin options are available for each species, including veterinary registered products and human insulin preparations. The insulin chosen depends on the individual patient's requirements. Intermediate-acting insulin is usually the first choice for dogs, and longer-acting insulin is the first choice for cats. Once the insulin type is chosen, the best method of insulin administration should be considered. Traditionally, insulin vials and syringes have been used, but insulin pen devices have recently entered the veterinary market. Pens have different handling requirements when compared with standard insulin vials including: storage out of the refrigerator for some insulin preparations once pen cartridges are in use; priming of the pen to ensure a full dose of insulin is administered; and holding the pen device in place for several seconds during the injection. Many different types of pen devices are available, with features such as half-unit dosing, large dials for visually impaired people, and memory that can display the last time and dose of insulin administered. Insulin pens come in both reusable and disposable options. Pens have several benefits over syringes, including improved dose accuracy, especially for low insulin doses. Keywords: diabetes, mellitus, canine, feline, NPH, glargine, porcine lente

Plasma resistin, adiponectin and leptin levels in relation to insulin resistance

International Nuclear Information System (INIS)

Shousha, M.A.; Soliman, S.E.T.

2010-01-01

Adipose tissue regulates insulin sensitivity via the circulating adipo cytokines, adiponectin, resistin and leptin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. We examined plasma levels of resistin, adiponectin and leptin in 20 lean subjects with mean body mass index (BMI) of 24, and, 36 nondiabetic obese individuals with mean BMI 34. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 30.4±6.5 vs. 14.4±2.9 mg/l, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P < 0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly reduced in obese compared with lean subjects, P < 0.005 and higher in women, P< 0.001. Adiponectin levels showed significant correlation with HOMA-R and this correlation remained significant after adjustment for gender and BMI. Leptin levels were significantly higher in obese subjects and women and correlated with resistin, but, didn't correlate with HOMA-R. In this small group of patients we demonstrated that insulin resistance correlated most strongly and reciprocally with adiponectin levels. Significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for leptin, the correlation with insulin resistance did not achieve statistical significance

49 CFR 23.3 - What do the terms used in this part mean?

Science.gov (United States)

2010-10-01

... BUSINESS ENTERPRISE IN AIRPORT CONCESSIONS General § 23.3 What do the terms used in this part mean... participation of firms in the ACDBE program. Airport Concession Disadvantaged Business Enterprise (ACDBE) means... management and daily business operations are controlled by one or more of the socially and economically...

Heart Rate Variability, Insulin Resistance, and Insulin Sensitivity in Japanese Adults: The Toon Health Study

Directory of Open Access Journals (Sweden)

Isao Saito

2015-09-01

Full Text Available Background: Although impaired cardiac autonomic function is associated with an increased risk of type 2 diabetes in Caucasians, evidence in Asian populations with a lower body mass index is limited. Methods: Between 2009–2012, the Toon Health Study recruited 1899 individuals aged 30–79 years who were not taking medication for diabetes. A 75-g oral glucose tolerance test was used to diagnose type 2 diabetes, and fasting and 2-h-postload glucose and insulin concentrations were measured. We assessed the homeostasis model assessment index for insulin resistance (HOMA-IR and Gutt’s insulin sensitivity index (ISI. Pulse was recorded for 5 min, and time-domain heart rate variability (HRV indices were calculated: the standard deviation of normal-to-normal intervals (SDNN and the root mean square of successive difference (RMSSD. Power spectral analysis provided frequency domain measures of HRV: high frequency (HF power, low frequency (LF power, and the LF:HF ratio. Results: Multivariate-adjusted logistic regression models showed decreased SDNN, RMSSD, and HF, and increased LF:HF ratio were associated significantly with increased HOMA-IR and decreased ISI. When stratified by overweight status, the association of RMSSD, HF, and LF:HF ratio with decreased ISI was also apparent in non-overweight individuals. The interaction between LF:HF ratio and decreased ISI in overweight individuals was significant, with the odds ratio for decreased ISI in the highest quartile of LF:HF ratio in non-overweight individuals being 2.09 (95% confidence interval, 1.41–3.10. Conclusions: Reduced HRV was associated with insulin resistance and lower insulin sensitivity. Decreased ISI was linked with parasympathetic dysfunction, primarily in non-overweight individuals.

Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization

DEFF Research Database (Denmark)

Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.

2012-01-01

An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...... in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic ß-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization...... and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization...

New ways of insulin delivery.

Science.gov (United States)

Heinemann, L

2010-02-01

When Exubera (EXU), the first inhaled insulin formulation to make it through the clinical development process, was introduced to the market some years ago it was hoped that this would be the first in a series of novel insulin formulations applied by this route. In addition, it was hoped that inhaled insulin would pave the way for other alternative routes of insulin administration (ARIA), i.e. oral insulin, nasal insulin or transdermal insulin to mention only some of the different attempts that have been studied in the last 90 years. The failure of EXU, i.e. its withdrawal from the market due to insufficient market success, was followed by the cessation of nearly all other attempts to develop inhaled insulin formulations. Currently there is only one company (MannKind) which moves sturdily ahead with their Technosphere insulin. This company has submitted an NDA for their product recently and hopes to bring it to the market by the end of 2010 or early 2011. Even if the product is able to pass the approval hurdles in the USA and Europe, this does not guarantee that it will become a market success. Many diabetologists were sceptical about the need/advantages of inhaled insulin/EXU from the start and the introduction of this product has raised even more scepticism. Reports about 'side effects' (development of lung cancer in patients treated with EXU) of inhaled insulin are also not helpful, even if the causality of the appearance of cancer with this type of insulin therapy is not proven. One of the very negative consequences of stopping EXU are the huge financial losses to Pfizer. The managers in charge in other pharmaceutical companies and also most venture capitalists are reluctant to invest in ARIA nowadays. This in turn means that many of the small companies that try to develop new forms of insulin administration have issues when they try to find a big brother and/or sufficient financial support. Clearly the economic crisis has further aggravated this issue. One can

Insulin analogues: have they changed insulin treatment and improved glycaemic control?

DEFF Research Database (Denmark)

Madsbad, Sten

2002-01-01

To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studies....... This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...... administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting...

Insulin structure and stability.

Science.gov (United States)

Brange, J; Langkjoer, L

1993-01-01

Insulin is composed of 51 amino acids in two peptide chains (A and B) linked by two disulfide bonds. The three-dimensional structure of the insulin molecule (insulin monomer), essentially the same in solution and in solid phase, exists in two main conformations. These differ in the extent of helix in the B chain which is governed by the presence of phenol or its derivatives. In acid and neutral solutions, in concentrations relevant for pharmaceutical formulation, the insulin monomer assembles to dimers and at neutral pH, in the presence of zinc ions, further to hexamers. Many crystalline modifications of insulin have been identified but only those with the hexamer as the basic unit are utilized in preparations for therapy. The insulin hexamer forms a relatively stable unit but some flexibility remains within the individual molecules. The intrinsic flexibility at the ends of the B chain plays an important role in governing the physical and chemical stability of insulin. A variety of chemical changes of the primary structure (yielding insulin derivatives), and physical modifications of the secondary to quaternary structures (resulting in "denaturation," aggregation, and precipitation) are known to affect insulin and insulin preparations during storage and use (Fig. 8). The tendency of insulin to undergo structural transformation resulting in aggregation and formation of insoluble insulin fibrils has been one of the most intriguing and widely studied phenomena in relation to insulin stability. Although the exact mechanism of fibril formation is still obscure, it is now clear that the initial step is an exposure of certain hydrophobic residues, normally buried in the three-dimensional structure, to the surface of the insulin monomer. This requires displacement of the COOH-terminal B-chain residues from their normal position which can only be accomplished via monomerization of the insulin. Therefore, most methods stabilizing insulin against fibrillation share the

Alteration in insulin action

DEFF Research Database (Denmark)

Tanti, J F; Gual, P; Grémeaux, T

2004-01-01

Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

DEFF Research Database (Denmark)

Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

2005-01-01

In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... endogenous insulin secretion, which was estimated by deconvolution of C-peptide concentrations. Hepatic extraction of insulin was calculated as 1 minus the ratio of fasting posthepatic insulin delivery rate to fasting endogenous insulin secretion rate. Compared with controls, LIPO displayed increased fasting...... insulin (130%, P Hepatic extraction of insulin was similar between groups (LIPO, 55%; controls, 57%; P > .8). In LIPO, HEXi and MCRi correlated inversely with fasting insulin (r = -0.56, P

Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization.

Directory of Open Access Journals (Sweden)

Tine N Vinther

Full Text Available An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic β-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization to form the structural equivalent of the classical hexamer. The covalently linked dimer neither bound to the insulin receptor, nor induced a metabolic response in vitro. However, it was extremely thermodynamically stable and did not form amyloid fibrils when subjected to mechanical stress, underlining the importance of oligomerization for insulin stability.

Binding Mode of Insulin Receptor and Agonist Peptide

Institute of Scientific and Technical Information of China (English)

无

2006-01-01

Insulin is a protein hormone secreted by pancreatic β cells. One of its main functions is to keep the balance of glucose inside the body by regulating the absorption and metabolism of glucose in the periphery tissue, as well as the production and storage of hepatic glycogen. The insulin receptor is a transmembrane glycoprotein in which two α subunits with a molecular weight of 135 kD and twoβ subunits with a molecular weight of 95 kD are joined by a disulfide bond to form a β-α-α-β structure. The extracellular α subunit, especially, its three domains near the N-terminal are partially responsible for signal transduction or ligand-binding, as indicated by the experiments. The extracellular α subunits are involved in binding the ligands. The experimental results indicate that the three domains of the N-terminal of the α subunits are the main determinative parts of the insulin receptor to bind the insulin or mimetic peptide.We employed the extracellular domain (PDBID: 1IGR) of the insulin-like growth factor-1 receptor (IGF-1 R ) as the template to simulate and optimize the spatial structures of the three domains in the extracellular domain of the insulin receptor, which includes 468 residues. The work was accomplished by making use of the homology program in the Insight Ⅱ package on an Origin3800 server. The docking calculations of the insulin receptor obtained by homology with hexapeptides were carried out by means of the program Affinity. The analysis indicated that there were hydrogen bonding, and electrostatic and hydrophobic effects in the docking complex of the insulin receptor with hexapeptides.Moreover, we described the spatial orientation of a mimetic peptide with agonist activity in the docking complex. We obtained a rough model of binding of DLAPSQ or STIVYS with the insulin receptor, which provides the powerful theoretical support for designing the minimal insulin mimetic peptide with agonist activity, making it possible to develop oral small

Long-term surface EMG monitoring using K-means clustering and compressive sensing

Science.gov (United States)

Balouchestani, Mohammadreza; Krishnan, Sridhar

2015-05-01

In this work, we present an advanced K-means clustering algorithm based on Compressed Sensing theory (CS) in combination with the K-Singular Value Decomposition (K-SVD) method for Clustering of long-term recording of surface Electromyography (sEMG) signals. The long-term monitoring of sEMG signals aims at recording of the electrical activity produced by muscles which are very useful procedure for treatment and diagnostic purposes as well as for detection of various pathologies. The proposed algorithm is examined for three scenarios of sEMG signals including healthy person (sEMG-Healthy), a patient with myopathy (sEMG-Myopathy), and a patient with neuropathy (sEMG-Neuropathr), respectively. The proposed algorithm can easily scan large sEMG datasets of long-term sEMG recording. We test the proposed algorithm with Principal Component Analysis (PCA) and Linear Correlation Coefficient (LCC) dimensionality reduction methods. Then, the output of the proposed algorithm is fed to K-Nearest Neighbours (K-NN) and Probabilistic Neural Network (PNN) classifiers in order to calclute the clustering performance. The proposed algorithm achieves a classification accuracy of 99.22%. This ability allows reducing 17% of Average Classification Error (ACE), 9% of Training Error (TE), and 18% of Root Mean Square Error (RMSE). The proposed algorithm also reduces 14% clustering energy consumption compared to the existing K-Means clustering algorithm.

Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects.

Science.gov (United States)

Kang, S; Creagh, F M; Peters, J R; Brange, J; Vølund, A; Owens, D R

1991-07-01

To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100). Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal. Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case). Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.

Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1–40/42 and Phospho-Tau May Abet Alzheimer Development

Science.gov (United States)

Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret

2016-01-01

Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat–fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1–40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1–40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. PMID:26895791

Generic Safety Requirements for Developing Safe Insulin Pump Software

Science.gov (United States)

Zhang, Yi; Jetley, Raoul; Jones, Paul L; Ray, Arnab

2011-01-01

Background The authors previously introduced a highly abstract generic insulin infusion pump (GIIP) model that identified common features and hazards shared by most insulin pumps on the market. The aim of this article is to extend our previous work on the GIIP model by articulating safety requirements that address the identified GIIP hazards. These safety requirements can be validated by manufacturers, and may ultimately serve as a safety reference for insulin pump software. Together, these two publications can serve as a basis for discussing insulin pump safety in the diabetes community. Methods In our previous work, we established a generic insulin pump architecture that abstracts functions common to many insulin pumps currently on the market and near-future pump designs. We then carried out a preliminary hazard analysis based on this architecture that included consultations with many domain experts. Further consultation with domain experts resulted in the safety requirements used in the modeling work presented in this article. Results Generic safety requirements for the GIIP model are presented, as appropriate, in parameterized format to accommodate clinical practices or specific insulin pump criteria important to safe device performance. Conclusions We believe that there is considerable value in having the diabetes, academic, and manufacturing communities consider and discuss these generic safety requirements. We hope that the communities will extend and revise them, make them more representative and comprehensive, experiment with them, and use them as a means for assessing the safety of insulin pump software designs. One potential use of these requirements is to integrate them into model-based engineering (MBE) software development methods. We believe, based on our experiences, that implementing safety requirements using MBE methods holds promise in reducing design/implementation flaws in insulin pump development and evolutionary processes, therefore improving

Insulin resistance in obesity can be reliably identified from fasting plasma insulin

NARCIS (Netherlands)

ter Horst, K. W.; Gilijamse, P. W.; Koopman, K. E.; de Weijer, B. A.; Brands, M.; Kootte, R. S.; Romijn, J. A.; Ackermans, M. T.; Nieuwdorp, M.; Soeters, M. R.; Serlie, M. J.

2015-01-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely

New Insulin Delivery Recommendations.

Science.gov (United States)

Frid, Anders H; Kreugel, Gillian; Grassi, Giorgio; Halimi, Serge; Hicks, Debbie; Hirsch, Laurence J; Smith, Mike J; Wellhoener, Regine; Bode, Bruce W; Hirsch, Irl B; Kalra, Sanjay; Ji, Linong; Strauss, Kenneth W

2016-09-01

Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Comparison of insulin lispro mix 25 with insulin lispro mix 50 as insulin starter in Chinese patients with type 2 diabetes mellitus (CLASSIFY study): Subgroup analysis of a Phase 4 open-label randomized trial.

Science.gov (United States)

Su, Qing; Liu, Chao; Zheng, Hongting; Zhu, Jun; Li, Peng Fei; Qian, Lei; Yang, Wen Ying

2017-06-01

Premixed insulins are recommended starter insulins in Chinese patients after oral antihyperglycemic medication (OAM) failure. In the present study, we compared the efficacy and safety of insulin lispro mix 25 (LM25) twice daily (b.i.d.) and insulin lispro mix 50 (LM50) b.i.d. as a starter insulin regimen in Chinese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with OAMs. The primary efficacy outcome in the present open-label parallel randomized clinical trial was change in HbA1c from baseline to 26 weeks. Patients were randomized in a ratio of 1:  1 to LM25 (n = 80) or LM50 (n = 76). A mixed-effects model with repeated measures was used to analyze continuous variables. The Cochran-Mantel-Haenszel test with stratification factor was used to analyze categorical variables. At the end of the study, LM50 was more efficacious than LM25 in reducing mean HbA1c levels (least-squares [LS] mean difference 0.48; 95 % confidence interval [CI] 0.22, 0.74; P 1). More subjects in the LM50 than LM25 group achieved HbA1c targets of 1) or ≤6.5 % (52.6 % vs 20.0 %; P 1). Furthermore, LM50 was more effective than LM25 at reducing HbA1c in patients with baseline HbA1c, blood glucose excursion, and postprandial glucose greater than or equal to median levels (P ≤ 0.001). The rate and incidence of hypoglycemic episodes and increase in weight at the end of the study were similar between treatment groups. In Chinese patients with T2DM, LM50 was more efficacious than LM25 as a starter insulin. © 2016 The Authors. Journal of Diabetes published by John Wiley & Sons Australia, Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

Evidence for altered transport of insulin across the blood-brain barrier in insulin-resistant humans.

Science.gov (United States)

Heni, Martin; Schöpfer, Patricia; Peter, Andreas; Sartorius, Tina; Fritsche, Andreas; Synofzik, Matthis; Häring, Hans-Ulrich; Maetzler, Walter; Hennige, Anita M

2014-08-01

Eating behavior, body weight regulation, peripheral glucose metabolism, and cognitive function depend on adequate insulin action in the brain, and recent studies in humans suggested that impaired insulin action in the brain emerges upon fat intake, obesity, and genetic variants. As insulin enters into the brain in a receptor-mediated fashion, we hypothesized that whole-body insulin sensitivity might affect the transport of insulin into the brain and contribute to the aversive effect of insulin resistance in the central nervous system. In this study, we aimed to determine the ratio of insulin in the cerebrospinal fluid and serum to whole-body insulin sensitivity. Healthy human subjects participated in an oral glucose tolerance test to determine whole-body insulin sensitivity and underwent lumbar puncture. Blood and CSF concentrations of insulin were significantly correlated. The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity with reduced insulin transported into the CSF in insulin-resistant subjects. Together, our data suggest that transport of insulin into the CSF relates to peripheral insulin sensitivity and impairs insulin action in the brain. This underlines the need for sensitizing measures in insulin-resistant subjects.

Comparison of a soluble co-formulation of insulin degludec/insulin aspart vs biphasic insulin aspart 30 in type 2 diabetes

DEFF Research Database (Denmark)

Niskanen, Leo; Leiter, Lawrence A; Franek, Edward

2012-01-01

Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of insulin degludec (70%) and insulin aspart (IAsp: 30%). Here, we compare the efficacy and safety of IDegAsp, an alternative IDegAsp formulation (AF: containing 45% IAsp), and biphasic IAsp 30 (BIAsp 30)....

Review of biphasic insulin aspart in the treatment of type 1 and 2 diabetes

Directory of Open Access Journals (Sweden)

Nazia Raja-Khan

2008-01-01

Full Text Available Nazia Raja-Khan, Sarah S Warehime, Robert A GabbayDivision of Endocrinology, Diabetes, and Metabolism, Penn State Institute for Diabetes and Obesity, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USABackground: Insulin is an effective treatment for achieving glycemic control and preventing complications in patients with diabetes. In order to make insulin therapy more acceptable to patients, newer formulations of insulin have been developed, such as biphasic insulins. Biphasic insulins conveniently provide both prandial and basal insulin in a single injection. One of the most well-studied biphasic insulins is biphasic insulin aspart 70/30.Objective: Our goal was to review the current literature on the safety and efficacy of biphasic insulin aspart in type 1 and type 2 diabetes.Methods: A MEDLINE search was conducted using the terms “biphasic insulin aspart” to identify clinical studies and reviews.Results: Biphasic insulin aspart more effectively reduces post-prandial glucose compared to other biphasic insulins and basal insulins. Compared to biphasic insulin aspart, fasting glucose levels are lower with NPH, similar with glargine, and similar or lower with biphasic human insulin. Treat-to-target trials have shown that a goal HbA1c below 6.5 or 7% can be achieved with biphasic insulin aspart. The risk of hypoglycemia is similar to or less than that seen with other biphasic insulins or NPH insulin.Conclusion: Biphasic insulin aspart 70/30 is a safe and effective treatment option for patients with diabetes.Keywords: biphasic insulin aspart, insulin, diabetes

Molecular Mechanisms of Insulin Secretion and Insulin Action.

Science.gov (United States)

Flatt, Peter R.; Bailey, Clifford J.

1991-01-01

Information and current ideas on the factors regulating insulin secretion, the mechanisms underlying the secretion and biological actions of insulin, and the main characteristics of diabetes mellitus are presented. (Author)

Insulin signaling disruption in male mice due to perinatal bisphenol A exposure: Role of insulin signaling in the brain.

Science.gov (United States)

Fang, Fangfang; Gao, Yue; Wang, Tingwei; Chen, Donglong; Liu, Jingli; Qian, Wenyi; Cheng, Jie; Gao, Rong; Wang, Jun; Xiao, Hang

2016-03-14

Bisphenol A (BPA), an environmental estrogenic endocrine disruptor, is widely used for producing polycarbonate plastics and epoxy resins. Available data have shown that perinatal exposure to BPA contributes to peripheral insulin resistance, while in the present study, we aimed to investigate the effects of perinatal BPA exposure on insulin signaling and glucose transport in the cortex of offspring mice. The pregnant mice were administrated either vehicle or BPA (100 μg/kg/day) at three perinatal stages. Stage I: from day 6 of gestation until parturition (P6-PND0 fetus exposure); Stage II: from lactation until delactation (PND0-PND21 newborn exposure) and Stage III: from day 6 of pregnancy until delactation (P6-PND21 fetus and newborn exposure). At 8 months of age for the offspring mice, the insulin signaling pathways and glucose transporters (GLUTs) were detected. Our data indicated that the insulin signaling including insulin, phosphorylated insulin receptor (IR), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular signal regulated protein kinase (p-ERK) were significantly decreased in the brain. In parallel, GLUTs (GLUT1/3/4) were obviously decreased as well in BPA-treated group in mice brain. Noteworthily, the phosphorylated tau (p-tau) and amyloid precursor protein (APP) were markedly up-regulated in all BPA-treated groups. These results, taken together, suggest the adverse effects of BPA on insulin signaling and GLUTs, which might subsequently contribute to the increment of p-tau and APP in the brain of adult offspring. Therefore, perinatal BPA exposure might be a risk factor for the long-term neurodegenerative changes in offspring male mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Insulin in human milk and the use of hormones in infant formulas.

Science.gov (United States)

Shamir, Raanan; Shehadeh, Naim

2013-01-01

Human milk contains a substantial number of hormones and growth factors. Studies in animal models show that some of these peptides (e.g. insulin, insulin-like growth factor 1, IGF-1, epidermal growth factors) have an effect on the small intestine after orogastric administration. Recently, two efforts were made to incorporate growth factors into infant formulas. One of these efforts included the incorporation of IGF-1, and the second is an ongoing effort to evaluate the safety and efficacy of incorporating insulin into infant formulas. The rational and current evidence for adding insulin to infant formulas (presence in human milk, effects of orally administrated insulin on gut maturation, intestinal permeability, systemic effects and preliminary encouraging results of supplementing insulin to a preterm infant formula) is detailed in this review. If the addition of insulin to preterm infant formulas indeed results in better growth and accelerated intestinal maturation, future studies will need to address the supplementation of insulin in term infants and assess the efficacy of such supplementation in enhancing gut maturation and prevention of later noncommunicable diseases such as allergy, autoimmune diseases and obesity. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism.

Science.gov (United States)

Shin, Andrew C; Fasshauer, Martin; Filatova, Nika; Grundell, Linus A; Zielinski, Elizabeth; Zhou, Jian-Ying; Scherer, Thomas; Lindtner, Claudia; White, Phillip J; Lapworth, Amanda L; Ilkayeva, Olga; Knippschild, Uwe; Wolf, Anna M; Scheja, Ludger; Grove, Kevin L; Smith, Richard D; Qian, Wei-Jun; Lynch, Christopher J; Newgard, Christopher B; Buettner, Christoph

2014-11-04

Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain α-keto acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors in mice demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Short-term overfeeding impairs the ability of brain insulin to lower BCAAs in rats. High-fat feeding in nonhuman primates and obesity and/or diabetes in humans is associated with reduced BCKDH protein in liver. These findings support the concept that decreased hepatic BCKDH is a major cause of increased plasma BCAAs and that hypothalamic insulin resistance may account for impaired BCAA metabolism in obesity and diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

Insulin in Central Nervous System: More than Just a Peripheral Hormone

Directory of Open Access Journals (Sweden)

Ana I. Duarte

2012-01-01

Full Text Available Insulin signaling in central nervous system (CNS has emerged as a novel field of research since decreased brain insulin levels and/or signaling were associated to impaired learning, memory, and age-related neurodegenerative diseases. Thus, besides its well-known role in longevity, insulin may constitute a promising therapy against diabetes- and age-related neurodegenerative disorders. More interestingly, insulin has been also faced as the potential missing link between diabetes and aging in CNS, with Alzheimer's disease (AD considered as the “brain-type diabetes.” In fact, brain insulin has been shown to regulate both peripheral and central glucose metabolism, neurotransmission, learning, and memory and to be neuroprotective. And a future challenge will be to unravel the complex interactions between aging and diabetes, which, we believe, will allow the development of efficient preventive and therapeutic strategies to overcome age-related diseases and to prolong human “healthy” longevity. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: diabetes and AD, both in terms of intracellular signaling and potential therapeutic approach.

Insulin Biosynthetic Interaction Network Component, TMEM24, Facilitates Insulin Reserve Pool Release

Directory of Open Access Journals (Sweden)

Anita Pottekat

2013-09-01

Full Text Available Insulin homeostasis in pancreatic β cells is now recognized as a critical element in the progression of obesity and type II diabetes (T2D. Proteins that interact with insulin to direct its sequential synthesis, folding, trafficking, and packaging into reserve granules in order to manage release in response to elevated glucose remain largely unknown. Using a conformation-based approach combined with mass spectrometry, we have generated the insulin biosynthetic interaction network (insulin BIN, a proteomic roadmap in the β cell that describes the sequential interacting partners of insulin along the secretory axis. The insulin BIN revealed an abundant C2 domain-containing transmembrane protein 24 (TMEM24 that manages glucose-stimulated insulin secretion from a reserve pool of granules, a critical event impaired in patients with T2D. The identification of TMEM24 in the context of a comprehensive set of sequential insulin-binding partners provides a molecular description of the insulin secretory pathway in β cells.

Novel Roles for the Insulin-Regulated Glucose Transporter-4 in Hippocampally Dependent Memory.

Science.gov (United States)

Pearson-Leary, Jiah; McNay, Ewan C

2016-11-23

The insulin-regulated glucose transporter-4 (GluT4) is critical for insulin- and contractile-mediated glucose uptake in skeletal muscle. GluT4 is also expressed in some hippocampal neurons, but its functional role in the brain is unclear. Several established molecular modulators of memory processing regulate hippocampal GluT4 trafficking and hippocampal memory formation is limited by both glucose metabolism and insulin signaling. Therefore, we hypothesized that hippocampal GluT4 might be involved in memory processes. Here, we show that, in male rats, hippocampal GluT4 translocates to the plasma membrane after memory training and that acute, selective intrahippocampal inhibition of GluT4-mediated glucose transport impaired memory acquisition, but not memory retrieval. Other studies have shown that prolonged systemic GluT4 blockade causes insulin resistance. Unexpectedly, we found that prolonged hippocampal blockade of glucose transport through GluT4-upregulated markers of hippocampal insulin signaling prevented task-associated depletion of hippocampal glucose and enhanced both working and short-term memory while also impairing long-term memory. These effects were accompanied by increased expression of hippocampal AMPA GluR1 subunits and the neuronal GluT3, but decreased expression of hippocampal brain-derived neurotrophic factor, consistent with impaired ability to form long-term memories. Our findings are the first to show the cognitive impact of brain GluT4 modulation. They identify GluT4 as a key regulator of hippocampal memory processing and also suggest differential regulation of GluT4 in the hippocampus from that in peripheral tissues. The role of insulin-regulated glucose transporter-4 (GluT4) in the brain is unclear. In the current study, we demonstrate that GluT4 is a critical component of hippocampal memory processes. Memory training increased hippocampal GluT4 translocation and memory acquisition was impaired by GluT4 blockade. Unexpectedly, whereas long-term

Identification of residues in the insulin molecule important for binding to insulin-degrading enzyme

Energy Technology Data Exchange (ETDEWEB)

Affholter, J.A.; Roth, R.A. (Stanford Univ. School of Medicine, CA (USA)); Cascieri, M.A.; Bayne, M.L. (Merck Sharp and Dohme Research Labs., Rahway, NJ (USA)); Brange, J. (Novo Research Institute, Bagsvaerd (Denmark)); Casaretto, M. (Deutsches Wollforschungsinstitut an der Technischen, Aachen (West Germany))

1990-08-21

Insulin-degrading enzyme (IDE) hydrolyzes insulin at a limited number of sites. Although the positions of these cleavages are known, the residues of insulin important in its binding to IDE have not been defined. To this end, the authors have studied the binding of a variety of insulin analogues to the protease in a solid-phase binding assay using immunoimmobilized IDE. Since IDE binds insulin with 600-fold greater affinity than it does insulin-like growth factor, the first set of analogues studied were hybrid molecules of insulin and IGF I. Removal of the eight amino acid D-chain region of IGF I (which has been predicted to interfere with binding to the 23-25 region) results in a 25-fold increase in affinity for IDE, confirming the importance of residues 23-25 in the high-affinity recognition of IDE. A similar role for the corresponding (B24-26) residues of insulin is supported by the use of site-directed mutant and semisynthetic insulin analogues. Insulin mutants (B25-Asp)insulin and (B25-His)insulin display 16- and 20-fold decreases in IDE affinity versus wild-type insulin. Similar decreases in affinity are observed with the C-terminal truncation mutants (B1-24-His{sup 25}-NH{sub 2})insulin and (B1-24-Leu{sup 25}-NH{sub 2})insulin, but not (B1-24-Trp{sup 25}-NH{sub 2})insulin and (B1-24-Tyr{sup 25}-NH{sub 2})insulin. The truncated analogue with the lowest affinity for IDE ((B1-24-His{sup 25}-NH{sub 2})insulin) has one of the highest affinities for the insulin receptor. Therefore, they have identified a region of the insulin molecule responsible for its high-affinity interaction with IDE. Although the same region has been implicated in the binding of insulin to its receptor, the data suggest that the structural determinants required for binding to receptor and IDE differ.

Identification of residues in the insulin molecule important for binding to insulin-degrading enzyme

International Nuclear Information System (INIS)

Affholter, J.A.; Roth, R.A.; Cascieri, M.A.; Bayne, M.L.; Brange, J.; Casaretto, M.

1990-01-01

Insulin-degrading enzyme (IDE) hydrolyzes insulin at a limited number of sites. Although the positions of these cleavages are known, the residues of insulin important in its binding to IDE have not been defined. To this end, the authors have studied the binding of a variety of insulin analogues to the protease in a solid-phase binding assay using immunoimmobilized IDE. Since IDE binds insulin with 600-fold greater affinity than it does insulin-like growth factor, the first set of analogues studied were hybrid molecules of insulin and IGF I. Removal of the eight amino acid D-chain region of IGF I (which has been predicted to interfere with binding to the 23-25 region) results in a 25-fold increase in affinity for IDE, confirming the importance of residues 23-25 in the high-affinity recognition of IDE. A similar role for the corresponding (B24-26) residues of insulin is supported by the use of site-directed mutant and semisynthetic insulin analogues. Insulin mutants [B25-Asp]insulin and [B25-His]insulin display 16- and 20-fold decreases in IDE affinity versus wild-type insulin. Similar decreases in affinity are observed with the C-terminal truncation mutants [B1-24-His 25 -NH 2 ]insulin and [B1-24-Leu 25 -NH 2 ]insulin, but not [B1-24-Trp 25 -NH 2 ]insulin and [B1-24-Tyr 25 -NH 2 ]insulin. The truncated analogue with the lowest affinity for IDE ([B1-24-His 25 -NH 2 ]insulin) has one of the highest affinities for the insulin receptor. Therefore, they have identified a region of the insulin molecule responsible for its high-affinity interaction with IDE. Although the same region has been implicated in the binding of insulin to its receptor, the data suggest that the structural determinants required for binding to receptor and IDE differ

Continuation versus discontinuation of insulin secretagogues when initiating insulin in type 2 diabetes

NARCIS (Netherlands)

Swinnen, S. G.; Dain, M.-P.; Mauricio, D.; DeVries, J. H.; Hoekstra, J. B.; Holleman, F.

2010-01-01

We compared the combined use of basal insulin, metformin and insulin secretagogues with a combination of basal insulin and metformin in patients with type 2 diabetes starting basal insulin analogue therapy. This analysis was part of a 24-week trial, in which 964 insulin-naive patients with type 2

Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients.

Science.gov (United States)

Hu, Xiaolei; Chen, Fengling

2018-01-01

Insulin has been used for diabetes therapy and has achieved significant therapeutic effect. In recent years, the use of purified and recombinant human insulin preparations has markedly reduced, but not completely suppressed, the incidence of insulin antibodies (IAs). IAs induced by exogenous insulin in diabetic patients is associated with clinical events, which is named exogenous insulin antibody syndrome (EIAS). The present review is based on our research and summarizes the characterization of IAs, the factors affecting IA development, the clinical significance of IAs and the treatments for EIAS. © 2018 The authors.

Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1-40/42 and Phospho-Tau May Abet Alzheimer Development.

Science.gov (United States)

Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret; Farese, Robert V

2016-07-01

Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat-fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1-40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1-40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. © 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.

Immunocytochemical detection of glucagon and insulin cells in ...

Indian Academy of Sciences (India)

Madhu urs

throughout the pancreas during the reproductive cycle, while insulin-IR cells were found to be pulsating in their secretion. Mean size ..... The interaction effect between the species .... Singh D P 1974 Analysis of environmental factors regulating.

Failure to increase insulin secretory capacity during pregnancy-induced insulin resistance is associated with ethnicity and gestational diabetes.

Science.gov (United States)

Mørkrid, Kjersti; Jenum, Anne K; Sletner, Line; Vårdal, Mari H; Waage, Christin W; Nakstad, Britt; Vangen, Siri; Birkeland, Kåre I

2012-10-01

To assess changes in insulin resistance and β-cell function in a multiethnic cohort of women in Oslo, Norway, from early to 28 weeks' gestation and 3 months post partum and relate the findings to gestational diabetes mellitus (GDM). Population-based cohort study of 695 healthy pregnant women from Western Europe (41%), South Asia (25%), Middle East (15%), East Asia (6%) and elsewhere (13%). Blood samples and demographics were recorded at mean 15 (V1) and 28 (V2) weeks' gestation and 3 months post partum (V3). Universal screening was by 75 g oral glucose tolerance test at V2, GDM with modified IADPSG criteria (no 1-h measurement): fasting plasma glucose (PG) ≥5.1 or 2-h PG ≥8.5 mmol/l. Homeostatic model assessment (HOMA)-β (β-cell function) and HOMA-IR (insulin resistance) were calculated from fasting glucose and C-peptide. Characteristics were comparable across ethnic groups, except age (South Asians: younger, Pinsulin resistant than Western Europeans at V1. From V1 to V2, the increase in insulin resistance was similar across the ethnic groups, but the increase in β-cell function was significantly lower for the East and South Asians compared with Western Europeans. GDM women compared with non-GDM women were more insulin resistant at V1; from V1 to V2, their β-cell function increased significantly less and the percentage increase in β-cell function did not match the change in insulin resistance. Pregnant women from East Asia and South Asia were more insulin resistant and showed poorer HOMA-β-cell function than Western Europeans.

Effects of Endogenous Androgens and Abdominal Fat Distribution on the Interrelationship Between Insulin and Non-Insulin-Mediated Glucose Uptake in Females

Science.gov (United States)

Ezeh, Uche; Pall, Marita; Mathur, Ruchi; Dey, Damini; Berman, Daniel; Chen, Ida Y.; Dumesic, Daniel A.

2013-01-01

Background: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance. Glucose disposal occurs via noninsulin-mediated glucose uptake (NIMGU) and insulin-mediated glucose uptake (IMGU). It is unknown whether in PCOS NIMGU increases to compensate for declining IMGU and whether androgens and fat distribution influence this relationship. Objectives: The objective of the study was to compare in women with PCOS and controls the interrelationship between NIMGU [ie, glucose effectiveness (Sg)] and IMGU [ie, the insulin sensitivity index (Si)] and the role of androgens and fat distribution. Participants: Twenty-eight PCOS (by National Institutes of Health 1990 criteria) and 28 control (age, race, and body mass index matched) women were prospectively studied. A subset of 16 PCOS subjects and 16 matched controls also underwent abdominal computed tomography. Main Outcome Measures: Glucose disposal (by a frequently sampled iv glucose tolerance test), circulating androgens, and abdominal fat distribution [by waist to hip ratio and visceral (VAT) and sc (SAT) adipose tissue content] were measured. Results: PCOS women had lower mean Si and similar Sg and abdominal fat distribution compared with controls. PCOS women with Si below the PCOS median (more insulin resistant) had a lower mean Sg than controls with Si above the control median (more insulin sensitive). In PCOS only, body mass index, free T, modified Ferriman-Gallwey score, and waist to hip ratio independently predicted Sg, whereas Si did not. In PCOS, VAT and SAT independently and negatively predicted Si and Sg, respectively. Conclusion: The decreased IMGU in PCOS is not accompanied by a compensatory increase in NIMGU or associated with excessive VAT accumulation. Increased general obesity, SAT, and hyperandrogenism are primary predictors of the deterioration of NIMGU in PCOS. PMID:23450052

Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children.

Science.gov (United States)

Fram, Ricki Y; Cree, Melanie G; Wolfe, Robert R; Mlcak, Ronald P; Qian, Ting; Chinkes, David L; Herndon, David N

2010-06-01

To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits. Prospective, randomized study. An acute pediatric burn unit in a tertiary teaching hospital. Children, 4-18 yrs old, with total body surface area burned > or =40% and who arrived within 1 wk after injury were enrolled in the study. Patients were randomized to one of two groups. Intensive insulin therapy maintained blood glucose levels between 80 and 110 mg/dL. Conventional insulin therapy maintained blood glucose patients were included in the data analysis consisting of resting energy expenditure, whole body and liver insulin sensitivity, and skeletal muscle mitochondrial function. Studies were performed at 7 days postburn (pretreatment) and at 21 days postburn (posttreatment). Resting energy expenditure significantly increased posttreatment (1476 +/- 124 to 1925 +/- 291 kcal/m(2) x day; p = .02) in conventional insulin therapy as compared with a decline in intensive insulin therapy. Glucose infusion rate was identical between groups before treatment (6.0 +/- 0.8 conventional insulin therapy vs. 6.8 +/- 0.9 mg/kg x min intensive insulin therapy; p = .5). Intensive insulin therapy displayed a significantly higher glucose clamp infusion rate posttreatment (9.1 +/- 1.3 intensive insulin therapy versus 4.8 +/- 0.6 mg/kg x min conventional insulin therapy, p = .005). Suppression of hepatic glucose release was significantly greater in the intensive insulin therapy after treatment compared with conventional insulin therapy (5.0 +/- 0.9 vs. 2.5 +/- 0.6 mg/kg x min; intensive insulin therapy vs. conventional insulin therapy; p = .03). States 3 and 4 mitochondrial oxidation of palmitate significantly improved in intensive insulin therapy (0.9 +/- 0.1 to 1.7 +/- 0.1 microm O(2)/CS/mg protein/min for state 3, p = .004; and 0.7 +/- 0.1 to 1.3 +/- 0.1 microm O(2)/CS/mg protein/min for state 4, p protocol improves insulin sensitivity and mitochondrial

Insulin therapy in patients with cystic fibrosis in the pre-diabetes stage: a systematic review

Directory of Open Access Journals (Sweden)

Mariana Zorrón Mei Hsia Pu

Full Text Available Abstract Objective: To elucidate whether insulin is effective or not in patients with cystic fibrosis before the diabetes mellitus phase. Data source: The study was performed according to the Prisma method between August and September 2014, using the PubMed, Embase, Lilacs and SciELO databases. Prospective studies published in English, Portuguese and Spanish from 2002 to 2014, evaluating the effect of insulin on weight parameters, body mass index and pulmonary function in patients with cystic fibrosis, with a mean age of 17.37 years before the diabetes mellitus phase were included. Data synthesis: Eight articles were identified that included 180 patients undergoing insulin use. Sample size ranged from 4 to 54 patients, with a mean age ranging from 12.4 to 28 years. The type of follow-up, time of insulin use, the dose and implementation schedule were very heterogeneous between studies. Conclusions: There are theoretical reasons to believe that insulin has a beneficial effect in the studied population. The different methods and populations assessed in the studies do not allow us to state whether early insulin therapy should or should not be carried out in patients with cystic fibrosis prior to the diagnosis of diabetes. Therefore, studies with larger samples and insulin use standardization are required.

A sophisticated programmable miniaturised pump for insulin delivery.

Science.gov (United States)

Klein, J C; Slama, G

1980-09-01

We have conceived a truly pre-programmable infusion system usable for intravenous administration of insulin in diabetic subjects. The original system has been built into a small, commercially available, syringe-pump of which only the case and the mechanical parts have been kept. The computing until has a timer, a programmable memory of 512 words by 8 bits and a digital-to-frequency converter to run the motor which drives the syringe. The memory contains 8 profiles of insulin injections stored in digital form over 64 words. Each profile is selected by the patient before eating according to the carbohydrate content of the planned meal and last about two hours, starting from and returning to the basal rate of insulin, at which it remains until next profile selection. Amount, profiles and duration of insulin injection are either mean values deduced from previous studies with a closed-loop artificial pancreas or personally fitted values; they are stored in an instantly replaceable memory cell. This device allows the patient to choose the time, nature and amount of his food intake.

Efficacy and safety comparison between liraglutide as add-on therapy to insulin and insulin dose-increase in Chinese subjects with poorly controlled type 2 diabetes and abdominal obesity

Directory of Open Access Journals (Sweden)

Li Chun-jun

2012-11-01

Full Text Available Abstract Objective To assess the efficacy and safety of adding liraglutide to established insulin therapy in poorly controlled Chinese subjects with type 2 diabetes and abdominal obesity compared with increasing insulin dose. Methods A 12-week, randomized, parallel-group study was carried out. A total of 84 patients completed the trial who had been randomly assigned to either the liraglutide-added group or the insulin-increasing group while continuing current insulin based treatment. Insulin dose was reduced by 0-30% upon the initiation of liraglutide. Insulin doses were subsequently adjusted to optimized glycemic control. Glycosylated hemoglobin (HbA1c values, blood glucose, total daily insulin dose, body weight, waist circumference, and the number of hypoglycemic events and adverse events were evaluated. Results At the end of study, the mean reduction in HbA1c between the liraglutide-added group and the insulin-increasing group was not significantly different (1.9% vs. 1.77%, p>0.05. However, the percentage of subjects reaching the composite endpoint of HbA1c ≤ 7.0% with no weight gain and no hypoglycemia, was significantly higher in the liraglutide-added group than in the insulin-increasing group (67% vs. 19%, p2, p Conclusions Addition of liraglutide to abdominally obese, insulin-treated patients led to improvement in glycemic control similar to that achieved by increasing insulin dosage, but with a lower daily dose of insulin and fewer hypoglycemic events. Adding liraglutide to insulin also induced a significant reduction in body weight and waist circumference. Liraglutide combined with insulin may be the best treatment option for poorly controlled type 2 diabetes and abdominal obesity.