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

Abstract

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 (SI_clamp), oral glucose tolerance test, and fasting glucose and insulin. We compared surrogate insulin sensitivity indices to SI_clamp 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 SI_clamp did not differ significantly by CKD or obesity status. Adjusting for SI_clamp 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 SI_clamp, 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.