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Euglycaemic Hyperinsulinaemic Clamp (euglycaemic + hyperinsulinaemic_clamp)

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Medical Sciences70%
Life Sciences30%

Terms modified by Euglycaemic Hyperinsulinaemic Clamp

  • euglycaemic hyperinsulinaemic clamp technique
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    Selected Abstracts

    An increase in insulin sensitivity and basal beta-cell function in diabetic subjects treated with pioglitazone in a placebo-controlled randomized study

    DIABETIC MEDICINE, Issue 6 2004
    T. M. Wallace
    Abstract Aims To investigate the effect of treatment with pioglitazone on beta-cell function and insulin sensitivity in Type 2 diabetes. Methods Thirty subjects with diet-controlled Type 2 diabetes were randomized to 3 months treatment with pioglitazone (n = 19) or placebo (n = 11). All subjects underwent basal sampling for homeostatic model assessment (HOMA), followed by an intravenous glucose tolerance test and hyperglycaemic clamp, followed by an euglycaemic hyperinsulinaemic clamp; at baseline and after treatment. Results All results are expressed as mean (sem). Pioglitazone increased basal insulin sensitivity by 24.7% (7.8) HOMA-%S vs. 2.1% (5.9) in the placebo group (P = 0.02). Stimulated insulin sensitivity, M/I, increased in the pioglitazone group compared with placebo: +15.1 (2.8) l kg,1 min,1 vs. +3.2 (2.9) l kg,1 min,1, respectively (P = 0.009). Pioglitazone increased adiponectin by 39.3 (6.3), ng/ml compared with a decrease of 0.8 (1.3) ng/ml with placebo (P = 0.00004). HOMA-%B increased with pioglitazone, +11.5% (4.8) vs. ,2.0% (4.8) with placebo (P = 0.049), but there was no change in stimulated beta-cell function as determined by hyperglycaemic clamps. There was a significant reduction in the proinsulin/insulin ratio in the pioglitazone group, ,0.057 (0.02) compared with placebo, +0.004 (0.02) (P = 0.03). There was a significant reduction in HbA1c of 0.6% (0.1) in the pioglitazone group compared with placebo (P = 0.003). There was no significant weight gain associated with pioglitazone therapy: +0.7 (sem 0.6) kg vs. +1.1 (sem 0.5) kg in placebo group (P = NS). Conclusions Basal beta-cell function and insulin sensitivity improved following pioglitazone therapy. The improvement in proinsulin to insulin ratio suggests that beta-cells are under less stress. [source]

    Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance

    DIABETIC MEDICINE, Issue 5 2004
    S. M. A. Bennett
    Abstract Aims To determine the effects of rosiglitazone on insulin sensitivity, glucose tolerance and ambulatory blood pressure when administered to subjects with persistent impaired glucose tolerance (IGT). Methods Eighteen subjects with persistent IGT were randomized to receive rosiglitazone 4 mg twice daily or matching placebo for 12 weeks. Evaluation at baseline and at the end of treatment included measurement of whole body insulin sensitivity during a euglycaemic hyperinsulinaemic clamp and deriving an insulin sensitivity index. Changes in glucose and insulin concentration were determined after oral glucose tolerance test (OGTT) and mixed meal tolerance tests, and 24-h ambulatory blood pressure was monitored. Results Rosiglitazone significantly improved the insulin sensitivity index by 2.26 µg/kg per min per pmol/l relative to placebo (P = 0.0003). Four of nine subjects receiving rosiglitazone reverted to normal glucose tolerance and 5/9 remained IGT, although four of these had improved 2-h glucose values. In the placebo group, 1/9 subjects progressed to Type 2 diabetes and 8/9 remained IGT. Following OGTT and meal tolerance test, glucose and insulin area under curve were reduced over 3 and 4 h, respectively. Compared with placebo, ambulatory blood pressure decreased significantly in the rosiglitazone group by 10 mmHg systolic (P = 0.0066) and 8 mmHg diastolic (P = 0.0126). Conclusions Consistent with its effects in patients with Type 2 diabetes, rosiglitazone substantially improved whole body insulin sensitivity and the glycaemic and insulinaemic responses to an OGTT and meal tolerance test in subjects with persistent IGT. Furthermore, rosiglitazone reduced systolic and diastolic ambulatory blood pressure in these subjects. [source]

    Predictors of insulin sensitivity in Type 2 diabetes mellitus

    DIABETIC MEDICINE, Issue 7 2002
    E. Bonora
    Abstract Aims To identify the independent predictors of insulin sensitivity in Type 2 diabetes, and to establish whether isolated Type 2 diabetes (i.e. diabetes without overweight, dyslipidaemia and hypertension) is a condition of insulin resistance. Methods We examined 45 patients with non-insulin-treated Type 2 diabetes undergoing a 4-h euglycaemic hyperinsulinaemic clamp (20 mU/m2 per min) combined with 3H-3-D-glucose and 14C-U-glucose infusions and indirect calorimetry. We also examined 1366 patients with non-insulin-treated Type 2 diabetes randomly selected among those attending the Diabetes Clinic and in whom insulin resistance was estimated by Homeostasis Model Assessment (HOMA-IR). Results In the 45 patients undergoing glucose clamp studies, insulin-mediated total glucose disposal (TGD) was independently and negatively associated with systolic blood pressure (standardized , coefficient = ,0.407, P = 0.003), plasma triglycerides (,= ,0.355, P = 0.007), and HbA1c (,= ,0.350, P = 0.008). The overall variability of TGD explained by these variables was 53%. Overweight diabetic subjects with central fat distribution, hypertension, hypertriglyceridaemia and poor glycometabolic control had insulin-mediated TGD values markedly lower than their lean counterparts without hypertension, with normal triglycerides, and with good glycometabolic control (16 ± 5 vs. 31 ± 10 µmol/min per kg lean body mass, P < 0.01). Nevertheless, the latter still were markedly insulin-resistant when compared with sex- and age-matched non-diabetic control subjects (31 ± 10 vs. 54 ± 13 µmol/min per kg lean body mass, P < 0.01). In the 1366 Type 2 diabetic patients of the epidemiological study, HOMA-IR value was independently associated with HbA1c (, = 0.283, P < 0.0001), plasma triglycerides (, = 0.246, P < 0.0001), body mass index (, = 0.139, P < 0.001), waist girth (, = 0.124, P < 0.001) and hypertension (, = 0.066, P = 0.006). Conclusion Overweight, central fat distribution, dyslipidaemia, hypertension and poor glycometabolic control are strong independent predictors of insulin resistance in Type 2 diabetes. However, reduced insulin sensitivity can be found even when Type 2 diabetes is isolated and well controlled. Diabet. Med. 19, 535,542 (2002) [source]

    Metabolic effects of metformin in patients with impaired glucose tolerance

    DIABETIC MEDICINE, Issue 7 2001
    M. Lehtovirta
    Abstract Aims To assess the effect of metformin on insulin sensitivity, glucose tolerance and components of the metabolic syndrome in patients with impaired glucose tolerance (IGT). Methods Forty first-degree relatives of patients with Type 2 diabetes fulfilling WHO criteria for IGT and participating in the Botnia study in Finland were randomized to treatment with either metformin 500 mg b.i.d. or placebo for 6 months. An oral glucose tolerance test (OGTT) and a euglycaemic hyperinsulinaemic clamp in combination with indirect calorimetry was performed at 0 and 6 months. The patients were followed after stopping treatment for another 6 months in an open trial and a repeat OGTT was performed at 12 months. Results Metformin treatment resulted in a 20% improvement in insulin-stimulated glucose metabolism (from 28.7 ± 13 to 34.4 ± 10.7 µmol/kg fat-free mass (FFM)/min) compared with placebo (P = 0.01), which was primarily due to an increase in glucose oxidation (from 16.6 ± 3.6 to 19.1 ± 4.4 µmol/kg FFM; P = 0.03) These changes were associated with a minimal improvement in glucose tolerance, which was maintained after 12 months. Conclusions Metformin improves insulin sensitivity in subjects with IGT primarily by reversal of the glucose fatty acid cycle. Obviously large multicentre studies are needed to establish whether these effects are sufficient to prevent progression to manifest Type 2 diabetes and associated cardiovascular morbidity and mortality. Diabet. Med. 18, 578,583 (2001) [source]

    The effect of long-term exercise on glucose metabolism and peripheral insulin sensitivity in Standardbred horses

    EQUINE VETERINARY JOURNAL, Issue S36 2006
    E. de GRAAF-ROELFSEMA
    Summary Reasons for performing study: To study the possible long-term effect of improved glucose tolerance in horses after long-term training, as the impact of exercise training on glucose metabolism is still unclear in the equine species. It is not known whether there is a direct long-term effect of training or if the measurable effect on glucose metabolism is the residual effect of the last exercise session. Objectives: To determine the chronic effect on glucose metabolism and peripheral insulin sensitivity of long-term training in horses by use of the euglycaemic hyperinsulinaemic clamp technique. Methods: Eleven Standardbred horses were acclimatised to running on the high-speed treadmill for 4 weeks (Phase 1) followed by training for 18 weeks with an alternating endurance (, 60% HRmax) high intensity training programme (, 80% HRmax) (Phase 2). Training frequency was 4 days/week. At the end of Phase 1, a euglycaemic hyperinsulinaemic clamp was performed 72 h after the last bout of exercise in all horses. At the end of Phase 2, the horses were clamped 24 h or 72 h after the last bout of exercise. Results: Glucose metabolism rate did not change significantly after 18 weeks of training, measured 72 h after the last exercise bout (0.018 ± 0.009 and 0.022 ± 0.006 mmol/kg bwt/min, respectively). Peripheral insulin sensitivity also did not change significantly following training (7.6 ± 5.7 times 10,6 and 8.0 ± 3.1 times 10,6, respectively). The same measurements 24 h after the last bout of exercise showed no significant differences. Conclusions: Results indicated that long-term training in Standardbreds neither changed glucose metabolism or insulin sensitivity 72 h after the last bout of exercise. Potential relevance: The fact that the beneficial effect of increased insulin sensitivity after acute exercise diminishes quickly in horses and no long-term effects on insulin sensitivity after chronic exercise have as yet been found in horses, implies that exercise should be performed on a regular basis in horses to retain the beneficial effect of improved insulin sensitivity. [source]

    Adipose tissue gene expression in obese dogs after weight loss

    JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3 2008
    V. Leray
    Summary Body weight (BW) mainly depends on a balance between fat storage (lipogenesis) and fat mobilization (lipolysis) in adipocytes. BW changes play a role in insulin resistance (IR), the inability of insulin target tissue to respond to physiological levels of insulin. This results in inhibition of lipogenesis and stimulation of lipolysis. Weight gain leads to IR whereas, weight loss improves insulin sensitivity (IS). The aim of this study was to evaluate the effect of weight loss and recovery of IS on the expression of genes involved in lipogenesis and lipolysis in weight losing dogs. Gene expression was studied in both subcutaneous and visceral adipose tissue. Obese dogs received a hypoenergetic low fat high protein diet (0.6 × NRC recommendation). Before and after weight loss, IS was assessed using the euglycaemic hyperinsulinaemic clamp. Gene expression of IRS-2, SREBP, intracellular insulin effectors, ACC, FAS, FABP, ADRP, PEPCK, lipogenesis key proteins, perilipin and HSL, lipolysis key proteins were quantified using real-time RT-PCR in subcutaneous and visceral fat. BW decreased from 15.2 ± 0.5 to 11.4 ± 0.4 kg (p < 0.05) over 78 ± 8 days. When obese, dogs were insulin resistant. After weight loss, IS was improved. In the subcutaneous adipose tissue, the expression of only the IRS-2 was increased. In the visceral adipose tissue, the expression of the genes involved in the lipogenesis was decreased whereas one of the genes implied in the lipolysis did not change. The expression profile of genes involved in lipid metabolism, as measured after weight loss, is indicative for a lower lipogenesis after weight loss than in obese dogs. Our results also confirm dramatic differences in the lipid metabolism of visceral and subcutaneous fat. They should be completed by comparing gene expression during weight losing and normal weight steady state. [source]

    An insulin-resistant hypertriglyceridaemic normotensive obese dog model: assessment of insulin resistance by the euglycaemic hyperinsulinaemic clamp in combination with the stable isotope technique

    JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-4 2003
    E. Bailhache
    Summary Many studies have shown that in humans insulin resistance (IR) is associated with obesity and hypertriglyceridaemia. The aim of our study was to develop slowly dietary-induced obesity in dogs through long-term overfeeding of a high-fat diet, and to characterize this IR, hypertriglyceridaemic and normotensive model. Insulin resistance was assessed by the euglycaemic hyperinsulinaemic clamp technique. The contribution of hepatic glucose production during the clamp was evaluated using a constant stable-isotope-labelled glucose infusion. Overfeeding a high-fat diet for 7 months was associated with a 43 ± 5% body weight increase. Insulin resistance was characterized by hyperinsulinaemia in the unfed state (10 ± 1 vs. 24 ± 1 ,U/ml, in healthy and obese dogs, respectively, p < 0.02) and by a reduction of the insulin-mediated glucose uptake (28 ± 3 vs. 16 ± 1 mg/kg/min, p < 0.02). Hepatic glucose production suppression under insulin infusion allowed to conclude that this reduced glucose uptake resulted from a decrease of insulin sensitivity in obese dogs. Furthermore, animals remained normotensive and exhibited a marked hypertriglyceridaemia (0.26 ± 0.04 vs. 0.76 ± 0.15 mmol/l, in healthy and obese dogs, respectively, p < 0.02). Because hypertriglyceridaemia is the most common lipid abnormality in insulin-resistant humans, this dog with slowly induced obesity may constitute a good model to study the consequences of IR in lipid metabolism independently of vascular changes. [source]

    In vivo activity of 11,-hydroxysteroid dehydrogenase type 1 and free fatty acid-induced insulin resistance

    CLINICAL ENDOCRINOLOGY, Issue 4 2005
    K. Mai
    Summary Introduction, Free fatty acids (FFAs) induce hepatic insulin resistance and enhance hepatic gluconeogenesis. Glucocorticoids (GCs) also stimulate hepatic gluconeogenesis. The aim of this study was to investigate whether the FFA-induced hepatic insulin resistance is mediated by increased activity of hepatic 11,-hydroxysteroid dehydrogenase type 1 (11,-HSD1), accompanied by elevated hepatic cortisol levels. Methods, Following a 10-h overnight fast, six healthy male volunteers were investigated. A euglycaemic hyperinsulinaemic clamp was performed during lipid or saline infusion. To assess hepatic 11,-HSD1 activity, plasma cortisol levels were measured after oral administration of cortisone acetate during lipid or saline infusion. In addition, 11,-HSD activities were determined in vivo by calculating the urinary ratios of GC metabolites. Results, Lipid infusion increased FFAs (5·41 ± 1·00 vs. 0·48 ± 0·20 mmol/l; P < 0·005) and significantly increased insulin resistance [glucose infusion rate (GIR) 6·02 ± 2·60 vs. 4·08 ± 2·15 mg/kg/min; P < 0·005]. After lipid and saline infusions no changes in 11,-HSD1 activity were found, neither by changes in cortisone acetate to cortisol conversion nor by differences in urinary free cortisol (UFF) or cortisone (UFE), 5,-tetrahydrocortisol (THF), 5,-THF, cortisone (THE), UFF/UFE and (5,-THF + THF)/THE ratios. Conclusions, We found no change in hepatic and whole-body 11,-HSD1 activity during acute FFA-induced insulin resistance. Further studies are necessary to clarify whether 11,-HSD1 in muscle and adipose tissue is influenced by FFAs and whether 11,-HSD1 is involved in other conditions of insulin resistance. [source]

    Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV-infected patients receiving highly active antiretroviral therapy

    JOURNAL OF MEDICAL VIROLOGY, Issue 2 2008
    Ove Andersen
    Abstract Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV-infected patients, reflecting possibly a low-grade pro-inflammatory state. Low-grade inflammation has been implicated in insulin resistance and other features of dysmetabolism. Accordingly it is hypothesized that circulating suPAR is associated with the metabolic status of HIV-infected patients on HAART. Fasting plasma suPAR was determined in 36 normoglycaemic HIV-infected patients on HAART (n,=,18 lipodystrophic, and n,=,18 non-lipodystrophic) who had estimated insulin sensitivity (Rd) and non-oxidative glucose disposal (NOGM) by euglycaemic hyperinsulinaemic clamps, indirect calorimetry, and glucose tracer infusion. Five patients had circadian suPAR concentrations measured (24 hr, 20 min-intervals). suPAR and non-HDL-cholesterol were higher and Rd, NOGM, and limb fat were lower in lipodystrophic patients than in non-lipodystrophic patients (P,<,0.05). suPAR correlated positively with non-HDL-cholesterol and inversely with Rd, NOGM and limb fat (P,<,0.005, n,=,36). suPAR also correlated positively with leukocyte count and TNF-, (P,<,0.01, n,=,36) but not with IL-6. In multiple regression analyses suPAR was a stronger predictor of dysmetabolism than TNF-, and IL-6. Circadian suPAR did not systematically fluctuate. In conclusion, suPAR may reflect the metabolic status of the HIV-infected patient on HAART, thus linking low-grade inflammation, immune constitution, lipid and glucose metabolism, and fat redistribution. Circadian suPAR concentration appeared stable, suggesting that sampling schedule does not affect measurement. Further studies addressing whether suPAR predicts lipodystrophy and dysmetabolism in HIV-infected patients are warranted. J. Med. Virol. 80:209,216, 2008. © 2007 Wiley-Liss, Inc. [source]

    The addition of rosiglitazone to insulin in adolescents with type 1 diabetes and poor glycaemic control: a randomized-controlled trial

    PEDIATRIC DIABETES, Issue 4pt1 2008
    Monique L Stone
    Objective:, To evaluate the effect of rosiglitazone, an insulin sensitizer, on glycaemic control and insulin resistance in adolescents with type 1 diabetes mellitus (T1DM) Research design and methods:, Randomized, double-blind, placebo-controlled crossover trial of rosiglitazone (4 mg twice daily) vs. placebo (24 wk each, with a 4 wk washout period). Entry criteria were diabetes duration >1 yr, age 10,18 yr, puberty (,Tanner breast stage 2 or testicular volume >4 mL), insulin dose ,1.1 units/kg/day, and haemoglobin A1c (HbA1c) >8%. Responses to rosiglitazone were compared with placebo using paired t -tests. Results:, Of 36 adolescents recruited (17 males), 28 completed the trial. At baseline, age was 13.6 ± 1.8 yr, HbA1c 8.9 ± 0.96%, body mass index standard deviation scores (BMI-SDS) 0.94 ± 0.74 and insulin dose 1.5 ± 0.3 units/kg/day. Compared with placebo, rosiglitazone resulted in decreased insulin dose (5.8% decrease vs. 9.4% increase, p = 0.02), increased serum adiponectin (84.8% increase vs. 26.0% decrease, p < 0.01), increased cholesterol (+0.5 mmol/L vs. no change, p = 0.02), but no significant change in HbA1c (,0.3 vs. ,0.1, p = 0.57) or BMI-SDS (0.08 vs. 0.04, p = 0.31). Insulin sensitivity was highly variable in the seven subjects who consented to euglycaemic hyperinsulinaemic clamps. There were no major adverse effects attributable to rosiglitazone. Conclusion:, The addition of rosiglitazone to insulin did not improve HbA1c in this group of normal weight adolescents with T1DM. [source]