Fat mass largely contributes to insulin mediated glucose uptake in morbidly obese subjects

Objective: The aim of this study is to investigate the effect of body size on insulin-mediated, whole-body glucose uptake (M-value) in morbidly obese (MO) subjects, who have large amounts of fat mass. Furthermore, we aimed at verifying which surrogate insulin-sensitivity index can better substitute the euglycemic clamp values and whether the insulin secretion/insulin resistance index is meaningful also in MO subjects. Design: The study design is cross-sectional, case-control study of insulin sensitivity-assessed by different methods-and insulin secretion. Subjects: One-hundred and sixty-eight subjects ca. 39 years old, with a body mass index (BMI) between 17 and 64 kg m(-2), underwent euglycemic hyperinsulinemic clamp and oral glucose tolerance test (OGTT) with surrogate measures of insulin sensitivity together with body composition by (H2O)-H-3 dilution. Insulin secretion rate (ISR) was measured at fast and after OGTT by C-peptide deconvolution. Results: The population was divided into quartiles of BMI. In the fourth quartile, the best insulin-sensitivity variable between M/I/kg(FFM) and M/I/kg(bw) was the latter, as shown by area under the receiver-operator characteristic (ROC) curve (0.85 vs 0.89). The best index to identify insulin-resistant individuals (lowest distribution quartile: M/I/kg(bw) <= 29.3 mu mol min(-1) kg(-1) nmol l(-1)) were Matsuda index and oral glucose insulin sensitivity (OGIS), whereas fasting insulin concentration, QUICKI, and HOMA failed (ROC analysis). M-value declined exponentially as the BMI increased, whereas ISR linearly increased. The insulin secretion/insulin resistance index well applied to MO. Conclusion: In MO subjects, in which the fat mass is highly represented, fat-free mass cannot be considered the only determinant of insulin sensitivity, thus M-value should be normalized by total body weight. The best surrogates of insulin sensitivity measured by euglycemic clamp are Matsuda index and OGIS. BMI directly affects both insulin sensitivity and ISR and the insulin secretion/insulin resistance index is a valid model to correlate ISR with insulin sensitivity also in MO. International Journal of Obesity (2010) 34, 1726-1732; doi:10.1038/ijo.2010.99; published online 25 May 2010