Effect of body mass index and fat distribution on insulin sensitivity, secretion, and clearance in nonobese healthy men.

The effects of variation in body mass index (BMI; kg/m2) and body fat topography on insulin sensitivity, secretion, and clearance were determined in a group of 146 nonobese nondiabetic males. Volunteers underwent an i.v. glucose tolerance test, with determination of plasma glucose, insulin, and C-peptide levels. BMI was taken as a measure of overall adiposity, while skinfold thickness ratios were used to assess the centrality of fat distribution and the localization of central fat within the trunk. Measurements of insulin sensitivity, secretion, and clearance were obtained by mathematical modelling of the i.v. glucose tolerance test concentration profiles. Increasing BMI and centrality of fat distribution had no significant effect on glucose tolerance, but were independently associated with diminished insulin sensitivity and increased insulin secretion. The elevation in secretion occurred almost entirely during the second phase of pancreatic insulin release. These results show that the variations in insulin sensitivity and secretion that have often been reported in obesity are also present in a group within the normal range of BMI. However, the absence of any decrease in hepatic uptake, also reported in the obese, indicates that this might be an additional mechanism recruited to maintain glycemic control at higher levels of adiposity. Localization of central fat in the lower trunk was correlated with elevated first phase insulin secretion, but no concomitant change in insulin sensitivity. There may, therefore, be a direct effect of the distribution of central fat on insulin secretion.