Effect of Central Obesity on Regulation of Carbohydrate Metabolism in Obese Patients with Varying Degrees of Glucose Tolerance*

Abstract

It has been proposed that central obesity, by virtue of the enhanced lipolytic activity of abdominal adipose tissue, leads to higher plasma FFA concentrations, which, in turn, decrease both hepatic removal of insulin and insulinstimulated glucose uptake by peripheral tissues. In short, the predicted consequences of abdominal obesity are elevations in circulating FFA and insulin levels as well as insulin resistance. The goal of this study was to evaluate the relationships predicted by the overall hypothesis; this study was carried out in 31 obese females, defined as having normal glucose tolerance (n = 12), impaired glucose tolerance (n = 8), or noninsulin-dependent diabetes mellitus (n = 11). Abdominal obesity was estimated by determining the ratio of waist to hip girth, fasting and postprandial plasma FFA and insulin concentrations were measured at hourly intervals from 0800–1600 h, and insulin-stimulated glucose disposal was quantified by the euglycemic hyperinsulinemic clamp technique. The first step in the postulated sequence of events to be tested was that the greater the WHR, the higher the total integrated plasma FFA response. The correlation coefficient between these two variables was 0.29, indicating that the results did not support the prediction. Furthermore, we could not demonstrate any relationship between the magnitude of the plasma FFA and insulin responses (r = 0.20; P = NS). However, there was a modest inverse relationship between height of circulating plasma insulin concentration and a decrease in insulin-stimulated glucose uptake (r = −0.43; P < 0.03) in the group as a whole. On the other hand, when the three groups were analyzed individually, a significant inverse relationship was only seen in the control group (r = −0.67), and a direct relationship was actually seen in patients with impaired glucose tolerance (r = 0.88). Furthermore, when the mean responses for the variables in each of the three groups were compared, it was apparent that the postulated relationships between abdominal obesity, plasma FFA concentration, and insulin secretion and action were not present. Thus, the data presented do not support the hypothesis that differences in the degree of central obesity play an important role in regulation of plasma concentrations of either FFA or insulin or in modulation of insulin-stimulated glucose uptake in the patients we studied.