Roles of insulin resistance and obesity in regulation of plasma insulin concentrations

Plasma glucose, insulin, and C-peptide concentrations were determined in re sponse to graded infusions of glucose, and insulin secretion rates were cal culated over each sampling period. Measurements were also made of insulin c learance, resistance to insulin-mediated glucose, uptake, and the plasma gl ucose, insulin, and C-peptide concentrations at hourly intervals from 8:00 AM to 4:00 PM in response to breakfast and lunch. Plasma glucose, insulin, and C-peptide concentrations were significantly (P < 0.01) higher in obese women in response to the graded intravenous glucose infusion, associated wi th a 40% (P < 0.005) greater insulin secretory response. Degree of insulin resistance correlated positively (P < 0.05) with the increase in insulin se cretion rate in both nonobese (r = 0.52) and obese (r = 0.58) groups and in versely (P < 0.05) with the decrease in insulin clearance in obese (r = -0. 46) and nonobese (r = -0.39) individuals. Weight loss was associated with s ignificantly lower plasma glucose, insulin, and C-peptide concentrations in response to graded glucose infusions and in day-long insulin concentration s. Neither insulin resistance nor the insulin secretory response changed af ter weight loss, whereas there was a significant increase in the rate of in sulin clearance during the glucose infusion. It is concluded that 1) obesit y is associated with a shift to the left in the glucose-stimulated insulin secretory dose-response curve as well as a decrease in insulin clearance an d 2) changes in insulin secretion and insulin clearance in obese women are more a function of insulin resistance than obesity.