Hyperinsulinemia in the physiologic range is not superior to short-term fasting in suppressing insulin secretion in obese men

The negative-feedback control exerted by plasma insulin on beta -cell insul in release in normal-weight and obese subjects is still a matter of debate. Subjects submitted to a euglycemic insulin clamp undergo a suppression of insulin secretion that is due to both the infused insulin and the 2- to 3-h our fast during the procedure. We elected to elucidate the role of physiolo gic hyperinsulinemia per se in the insulin negative autofeedback in obese m en. Ten men with massive uncomplicated obesity (age, 18 to 37 years; body m ess index [BMI], 41 +/- 1.15 kg/m(2)) and 6 normal-weight healthy men (age, 22 to 30 years; BMI, 22 +/- 0.28 kg/m(2)) underwent 2 studies in random or der: (1) a euglycemic-hyperinsulinemic glucose clamp with an insulin infusi on rate of I mU/kg/min and (2) a control study with saline infusion. Serum C-peptide concentrations were significantly higher in obese versus control subjects at baseline (2.54 +/- 0.178 v 1.63 +/- 0.256 ng/mL, P < .05), Exog enous insulin infusion significantly suppressed serum C-peptide at steady s tate ([SS] last 30 minutes of insulin or saline infusion) in controls (mean of the last 4 measurements from 120 minutes to 150 minutes, 0.86 +/- 0.306 ng/mL, P < .05 v baseline) but not in obese patients (2.03 +/- 0.26 ng/mL, nonsignificant [NS] v baseline). During the saline infusion studies, C-pep tide levels slightly and similarly declined over time in both groups (2.71 +/- 0.350 at baseline v 2.31 +/- 0.300 ng/mL at SS in obese patients, NS, a nd 1.96 rt 0.189 v 1.62 +/- 0.150 ng/mL in controls, NS). This study shows that in obese men hyperinsulinemia within the postprandial range is not sup erior to a 2.5-hour fast for the suppression of beta -cell activity, sugges ting an impairment of the insulin negative autofeedback in this clinical co ndition, Copyright (C) 2001 by W.B. Saunders Company.