Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats

Ranganath Muniyappa, Hui Chen, Radhika H. Muzumdar, Francine H. Einstein, Xu Yan, Lilly Q. Yue, Nir Barzilai, Michael J. Quon

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Assessing insulin resistance in rodent models gives insight into mechanisms that cause type 2 diabetes and the metabolic syndrome. The hyperinsulinemic euglycemic glucose clamp, the reference standard for measuring insulin sensitivity in humans and animals, is labor intensive and technically demanding. A number of simple surrogate indexes of insulin sensitivity/resistance have been developed and validated primarily for use in large human studies. These same surrogates are also frequently used in rodent studies. However, in general, these indexes have not been rigorously evaluated in animals. In a recent validation study in mice, we demonstrated that surrogates have a weaker correlation with glucose clamp estimates of insulin sensitivity/resistance than in humans. This may be due to increased technical difficulties in mice and/or intrinsic differences between human and rodent physiology. To help distinguish among these possibilities, in the present study, using data from rats substantially larger than mice, we compared the clamp glucose infusion rate (GIR) with surrogate indexes, including QUICKI, HOMA, 1/HOMA, log (HOMA), and 1/fasting insulin. All surrogates were modestly correlated with GIR (r = 0.34-0.40). Calibration analyses of surrogates adjusted for body weight demonstrated similar predictive accuracy for GIR among all surrogates. We conclude that linear correlations of surrogate indexes with clamp estimates and predictive accuracy of surrogate indexes in rats are similar to those in mice (but not as substantial as in humans). This additional rat study (taken with the previous mouse study) suggests that application of surrogate insulin sensitivity indexes developed for humans may not be appropriate for determining primary outcomes in rodent studies due to intrinsic differences in metabolic physiology. However, use of surrogates may be appropriate in rodents, where feasibility of clamps is an obstacle and measurement of insulin sensitivity is a secondary outcome.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume297
Issue number5
DOIs
StatePublished - Nov 2009

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Glucose Clamp Technique
Insulin Resistance
Rodentia
Glucose
Validation Studies
Type 2 Diabetes Mellitus
Calibration
Fasting
Body Weight
Insulin

Keywords

  • Calibration model
  • Glucose clamp
  • Quantitative insulin-sensitivity check index

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats. / Muniyappa, Ranganath; Chen, Hui; Muzumdar, Radhika H.; Einstein, Francine H.; Yan, Xu; Yue, Lilly Q.; Barzilai, Nir; Quon, Michael J.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 297, No. 5, 11.2009.

Research output: Contribution to journalArticle

Muniyappa, Ranganath ; Chen, Hui ; Muzumdar, Radhika H. ; Einstein, Francine H. ; Yan, Xu ; Yue, Lilly Q. ; Barzilai, Nir ; Quon, Michael J. / Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats. In: American Journal of Physiology - Endocrinology and Metabolism. 2009 ; Vol. 297, No. 5.
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