Relation between HOMA-IR and insulin sensitivity index determined by hyperinsulinemic-euglycemic clamp analysis during treatment with a sodium-glucose cotransporter 2 inhibitor

AbstractAimThe minor A allele of rs373863828 (CREBRF p.Arg457Gln) is associated with increased body mass index (BMI), but reduced risk of type 2 and gestational diabetes in Polynesian (Pacific peoples and Aotearoa New Zealand Māori) populations. This study investigates the effect of the A allele on insulin release and sensitivity in overweight/obese men without diabetes.MethodsA mixed meal tolerance test was completed by 172 men (56 with the A allele) of Māori or Pacific ancestry, and 44 (24 with the A allele) had a frequently sampled intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp. Mixed linear models with covariates age, ancestry and BMI were used to analyse the association between the A allele of rs373863828 and markers of insulin release and blood glucose regulation.ResultsThe A allele of rs373863828 is associated with a greater increase in plasma insulin 30 min following a meal challenge without affecting the elevation in plasma glucose or incretins GLP-1 or GIP. Consistent with this point, following an intravenous infusion of a glucose bolus, participants with an A allele had higher early (p<0.05 at 2 and 4 min) plasma insulin and C-peptide concentrations for a similar elevation in blood glucose as those homozygous for the major (G) allele. Despite increased plasma insulin, rs373863828 genotype was not associated with a significant difference (p>0.05) in insulin sensitivity index or glucose disposal during hyperinsulinemic-euglycemic clamp.Conclusion/interpretationrs373863828-A allele associates with increased glucose-stimulated insulin release without affecting insulin sensitivity, suggesting that CREBRF p.Arg457Gln may increase maximal ability for β-cells to release insulin to reduce the risk of type 2 diabetes.

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Evaluation of Insulin Sensitivity in Healthy Volunteers Treated with Olanzapine, Risperidone, or Placebo: A Prospective, Randomized Study Using the Two-Step Hyperinsulinemic, Euglycemic Clamp

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2002-021884 ◽

2003 ◽

Vol 88 (12) ◽

pp. 5875-5880 ◽

Cited By ~ 50

Author(s):

Margaret Sowell ◽

Nitai Mukhopadhyay ◽

Patrizia Cavazzoni ◽

Christopher Carlson ◽

Sunder Mudaliar ◽

...

Keyword(s):

Insulin Sensitivity ◽

Healthy Subjects ◽

Tolerance Test ◽

Glucose Disposal ◽

Sensitivity Index ◽

Mixed Meal ◽

Meal Tolerance Test ◽

Euglycemic Clamp ◽

Hyperinsulinemic Euglycemic Clamp ◽

Mixed Meal Tolerance Test

Abstract The primary objective of this study was to evaluate insulin sensitivity in healthy subjects treated with olanzapine or risperidone. Subjects were randomly assigned to single-blind therapy with olanzapine (10 mg/d), risperidone (4 mg/d), or placebo for approximately 3 wk. Insulin sensitivity was assessed pre- and posttreatment using a 2-step, hyperinsulinemic, euglycemic clamp. Glucose and insulin responses were also assessed by a mixed meal tolerance test. Of the 64 subjects randomized, 22, 14, and 19 in the olanzapine, risperidone, and placebo groups, respectively, completed the study procedures. There were no significant within-group changes in the glucose disposal rate or the insulin sensitivity index for the active therapy groups. Further, the results of the mixed meal tolerance test did not demonstrate clinically significant changes in integrated glucose metabolism during treatment with these medications. In summary, this study did not demonstrate significant changes in insulin sensitivity in healthy subjects after 3 wk of treatment with olanzapine or risperidone.

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A Novel Use of the Hyperinsulinemic-Euglycemic Clamp Technique to Estimate Insulin Sensitivity of Systemic Lipolysis

Hormone and Metabolic Research ◽

10.1055/s-2001-12403 ◽

2001 ◽

Vol 33 (2) ◽

pp. 89-95 ◽

Cited By ~ 11

Author(s):

M Stumvoll ◽

H G Wahl ◽

K Löblein ◽

R Becker ◽

A Volk ◽

...

Keyword(s):

Insulin Sensitivity ◽

Euglycemic Clamp ◽

Clamp Technique ◽

Hyperinsulinemic Euglycemic Clamp

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Chronic kidney disease and obesity bias surrogate estimates of insulin sensitivity compared with the hyperinsulinemic euglycemic clamp

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00394.2016 ◽

2017 ◽

Vol 312 (3) ◽

pp. E175-E182 ◽

Cited By ~ 2

Author(s):

Iram Ahmad ◽

Leila R. Zelnick ◽

Nicole R. Robinson ◽

Adriana M. Hung ◽

Bryan Kestenbaum ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Insulin Sensitivity ◽

Kidney Disease ◽

Oral Glucose ◽

Cross Sectional ◽

Euglycemic Clamp ◽

Insulin Kinetics ◽

Hyperinsulinemic Euglycemic Clamp ◽

Sensitivity Indices ◽

Organ Specific

Insulin sensitivity can be measured by procedures such as the hyperinsulinemic euglycemic clamp or by using surrogate indices. Chronic kidney disease (CKD) and obesity may differentially affect these measurements because of changes in insulin kinetics and organ-specific effects on insulin sensitivity. In a cross-sectional study of 59 subjects with nondiabetic CKD [estimated glomerular filtration rate: (GFR) <60 ml·min−1·1.73 m2] and 39 matched healthy controls, we quantified insulin sensitivity by clamp (SIclamp), oral glucose tolerance test, and fasting glucose and insulin. We compared surrogate insulin sensitivity indices to SIclamp using descriptive statistics, graphical analyses, correlation coefficients, and linear regression. Mean age was 62.6 yr; 48% of the participants were female, and 77% were Caucasian. Insulin sensitivity indices were 8–38% lower in participants with vs. without CKD and 13–59% lower in obese compared with nonobese participants. Correlations of surrogate indices with SIclamp did not differ significantly by CKD or obesity status. Adjusting for SIclamp in addition to demographic factors, Matsuda index was 15% lower in participants with vs. without CKD ( P = 0.09) and 36% lower in participants with vs. without obesity ( P = 0.0001), whereas 1/HOMA-IR was 23% lower in participants with vs. without CKD ( P = 0.02) and 46% lower in participants with vs. without obesity ( P < 0.0001). We conclude that CKD and obesity do not significantly alter correlations of surrogate insulin sensitivity indices with SIclamp, but they do bias surrogate measurements of insulin sensitivity toward lower values. This bias may be due to differences in insulin kinetics or organ-specific responses to insulin.

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Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp.

Journal of Clinical Investigation ◽

10.1172/jci112886 ◽

1987 ◽

Vol 79 (3) ◽

pp. 790-800 ◽

Cited By ~ 481

Author(s):

R N Bergman ◽

R Prager ◽

A Volund ◽

J M Olefsky

Keyword(s):

Insulin Sensitivity ◽

Minimal Model ◽

Glucose Clamp ◽

Sensitivity Index ◽

Insulin Sensitivity Index ◽

Model Method

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Postprandial glucose fluxes and insulin sensitivity during exercise: A study in healthy individuals

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00182.2013 ◽

2013 ◽

Vol 305 (4) ◽

pp. E557-E566 ◽

Cited By ~ 22

Author(s):

Michele Schiavon ◽

Ling Hinshaw ◽

Ashwini Mallad ◽

Chiara Dalla Man ◽

Giovanni Sparacino ◽

...

Keyword(s):

Insulin Sensitivity ◽

Healthy Subjects ◽

Acute Exercise ◽

Glucose Production ◽

Endogenous Glucose Production ◽

Fat Free Mass ◽

Glucose Turnover ◽

Sensitivity Index ◽

Moderate Exercise ◽

Insulin Sensitivity Index

Quantifying the effect size of acute exercise on insulin sensitivity (SIexercise) and simultaneous measurement of glucose disappearance (Rd), endogenous glucose production (EGP), and meal glucose appearance in the postprandial state has not been developed in humans. To do so, we studied 12 healthy subjects [5 men, age 37.1 ± 3.1 yr, body mass index 24.1 ± 1.1 kg/m2, fat-free mass (FFM) 50.9 ± 3.9 kg] during moderate exercise at 50% V̇o2max for 75 min, 120–195 min after a triple-tracer mixed meal consumed at time 0. Tracer infusion rates were adjusted to achieve constant tracer-to-tracee ratio and minimize non-steady-state errors. Glucose turnover was estimated by accounting for the nonstationary kinetics introduced by exercise. Insulin sensitivity index was calculated in each subject both in the absence [time ( t) = 0–120 min, SIrest] and presence ( t = 0–360 min, SIexercise) of physical activity. EGP at t = 0 min (13.4 ± 1.1 μM·kg FFM−1·min−1) fell at t = 120 min (2.4 ± 0.4 μM·kg FFM−1·min−1) and then rapidly rose almost eightfold at t = 180 min (18.2 ± 2.6 μM·kg FFM−1·min−1) before gradually falling at t = 360 min (10.6 ± 0.9 μM·kg FFM−1·min−1). Rd rapidly peaked at t = 120 min at the start of exercise (89.5 ± 11.6 μM·kg FFM−1·min−1) and then gradually declined at t = 195 min (26.4 ± 3.3 μM·kg FFM−1·min−1) before returning to baseline at t = 360 min. SIexercise was significantly higher than SIrest (21.6 ± 3.7 vs. 12.5 ± 2.0 10−4 dl·kg−1·min−1 per μU/ml, P < 0.0005). Glucose turnover was estimated for the first time during exercise with the triple-tracer technique. Our results, applying state-of-the-art techniques, show that moderate exercise almost doubles postprandial insulin sensitivity index in healthy subjects.

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Associations of phthalate exposure with lipid levels and insulin sensitivity index in children: A prospective cohort study

The Science of The Total Environment ◽

10.1016/j.scitotenv.2019.01.151 ◽

2019 ◽

Vol 662 ◽

pp. 714-721 ◽

Cited By ~ 5

Author(s):

Hyejin Han ◽

Hye Ah Lee ◽

Bohyun Park ◽

Bomi Park ◽

Young Sun Hong ◽

...

Keyword(s):

Cohort Study ◽

Insulin Sensitivity ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Sensitivity Index ◽

Lipid Levels ◽

Insulin Sensitivity Index ◽

Phthalate Exposure

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Superimposition of Postnatal Calorie Restriction Protects the Aging Male Intrauterine Growth- Restricted Offspring from Metabolic Maladaptations

Endocrinology ◽

10.1210/en.2012-1206 ◽

2012 ◽

Vol 153 (9) ◽

pp. 4216-4226 ◽

Cited By ~ 16

Author(s):

Yun Dai ◽

Shanthie Thamotharan ◽

Meena Garg ◽

Bo-Chul Shin ◽

Sherin U. Devaskar

Keyword(s):

Physical Activity ◽

Insulin Sensitivity ◽

Postnatal Growth ◽

Growth Restriction ◽

Fine Tuning ◽

Whole Body ◽

Aging Male ◽

Intrauterine Growth ◽

Euglycemic Clamp ◽

Hyperinsulinemic Euglycemic Clamp

Intrauterine growth restriction (IUGR) results in dysregulated glucose homeostasis and adiposity in the adult. We hypothesized that with aging, these perturbations will wane, and superimposition of postnatal growth restriction (PNGR) on IUGR [intrauterine and postnatal growth restriction (IPGR)] will reverse the residual IUGR phenotype. We therefore undertook hyperinsulinemic-euglycemic clamp, energy balance, and physical activity studies during fed, fasted, and refed states, in light and dark cycles, on postweaned chow diet-fed more than 17-month aging male IUGR, PNGR, and IPGR vs. control (CON) rat offspring. Hyperinsulinemic-euglycemic clamp revealed similar whole-body insulin sensitivity and physical activity in the nonobese IUGR vs. CON, despite reduced heat production and energy expenditure. Compared with CON and IUGR, IPGR mimicking PNGR was lean and growth restricted with increased physical activity, O2 consumption (VO2), energy intake, and expenditure. Although insulin sensitivity was no different in IPGR and PNGR, skeletal muscle insulin-induced glucose uptake was enhanced. This presentation proved protective against the chronologically earlier (5.5 months) development of obesity and dysregulated energy homeostasis after 19 wk on a postweaned high-fat diet. This protective role of PNGR on the metabolic IUGR phenotype needs future fine tuning aimed at minimizing unintended consequences.

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