Submitted on October 22, 2007
Accepted on November 9, 2007
Comparison Between Surrogate Indexes of Insulin Sensitivity/Resistance and Hyperinsulinemic-Euglycemic Clamp Estimates in Mice
Sihoon Lee1, Ranganath Muniyappa2, Xu Yan3, Hui Chen1, Lilly Q Yue3, Eun-Gyoung Hong4, Jason K Kim4, and Michael J. Quon5*
1 NCCAM, NIH, Bethesda, Maryland, United States
2 NCCAM, NIH, Bethesda, Maryland, United States; Laboratory of Clinical Investigation, NCCAM, NIH, 10-CRC-Hatfield Clinical Research, Room 4-1741, Bethesda, Maryland, 20892-1302, United States
3 Division of Biostatistics, FDA, Rockville, Maryland, United States
4 Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States
5 NCCAM, NIH, Bethesda,, Maryland, United States; , United States
* To whom correspondence should be addressed. E-mail: quonm{at}nih.gov.
Insulin resistance contributes to the pathophysiology of diabetes, obesity, and their cardiovascular complications. Mouse models of these human diseases are useful for gaining insight into pathophysiological mechanisms. The reference standard for measuring insulin sensitivity in both humans and animals is the euglycemic glucose clamp. Many studies have compared surrogate indexes of insulin sensitivity/resistance with glucose clamp estimates in humans. However, regulation of metabolic physiology in humans and rodents differs and comparisons between surrogate indexes and the glucose clamp have not been directly evaluated in rodents previously. Therefore, in the present study, we compared glucose clamp-derived measures of insulin sensitivity (GIR and SIClamp) with surrogate indexes including QUICKI, HOMA, 1/HOMA, Log (HOMA), and 1/fasting insulin using data from 87 mice with a wide range of insulin sensitivities. We evaluated simple linear correlations and performed calibration model analyses to evaluate the predictive accuracy of each surrogate. All surrogate indexes tested were modestly correlated with both GIR and SIClamp. However, a stronger correlation between body weight per se and both GIR and SIClamp was noted. Calibration analyses of surrogate indexes adjusted for body weight demonstrated improved predictive accuracy for GIR (e.g., r = 0.68) for QUICKI and log (HOMA)). We conclude that linear correlations of surrogate indexes with clamp data and predictive accuracy of surrogate indexes in mice are not as substantial as in humans. This may reflect intrinsic differences between human and rodent physiology as well as increased technical difficulties in performing glucose clamps in mice.
