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

Abstract Context and Objective: Adipose tissue insulin resistance may cause hepatic and skeletal muscle insulin resistance by releasing excess free fatty acids (FFAs). Because no consensus exists on how to quantify adipose tissue insulin sensitivity we compared three methods for measuring adipose tissue insulin sensitivity: the single step insulin clamp, the multistep pancreatic clamp, and the adipose tissue insulin resistance index (Adipo-IR). Design and Participants: We studied insulin sensitivity in 25 adults by measuring the insulin concentration resulting in 50% suppression of palmitate flux (IC50) using both a multistep pancreatic clamp and a one-step hyperinsulinemic-euglycemic clamp. Palmitate kinetics were measured using a continuous infusion of [U-13C]palmitate. Adipo-IR was calculated from fasting insulin and fasting FFA concentrations. Results: Adipo-IR was reproducible (sample coefficient of variability, 10.0%) and correlated with the IC50 measured by the multistep pancreatic clamp technique (r, 0.86; P < 0.001). Age and physical fitness were significant predictors of the residual variation between Adipo-IR and IC50, with a positive relationship with age (r, 0.47; P = 0.02) and a negative association with VO2 peak (r, −0.46; P = 0.02). Likewise, IC50 measured by the multistep pancreatic clamp technique correlated with IC50 measured using the one-step hyperinsulinemic-euglycemic clamp technique (r, 0.73; P < 0.001). Conclusion: Adipo-IR and the one-step hyperinsulinemic-euglycemic clamp technique using a palmitate tracer are good predictors of a gold standard measure of adipose tissue insulin sensitivity. However, age and physical fitness systematically affect the predictive values. Although Adipo-IR is suitable for larger population studies, the multistep pancreatic clamp technique is probably needed for mechanistic studies of adipose tissue insulin action.

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Aspects of glucose homeostasis in uremia as assessed by the hyperinsulinemic euglycemic clamp technique

Metabolism ◽

10.1016/0026-0495(85)90213-6 ◽

1985 ◽

Vol 34 (5) ◽

pp. 465-473 ◽

Cited By ~ 30

Author(s):

O. Schmitz ◽

K.G.M.M. Alberti ◽

N.J. Christensen ◽

C. Hasling ◽

E. Hjøllund ◽

...

Keyword(s):

Glucose Homeostasis ◽

Euglycemic Clamp ◽

Clamp Technique ◽

Hyperinsulinemic Euglycemic Clamp

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Clenbuterol-Induced Insulin Resistance in Calves Measured by Hyperinsulinemic, Euglycemic Clamp Technique

Acta Veterinaria Scandinavica ◽

10.1186/bf03547800 ◽

1998 ◽

Vol 39 (2) ◽

pp. 281-289

Author(s):

K. Sternbauer ◽

J. Luthman ◽

A. Hänni ◽

SO. Jacobsson

Keyword(s):

Insulin Resistance ◽

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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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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