Feedback inhibition of insulin and glucagon secretion by insulin is altered in abdominal obesity with normal or impaired glucose tolerance.

We investigated the feedback inhibition of insulin and glucagon secretion during euglycemic-hyperinsulinemic clamp at about 350 pmol/l in 16 patients with abdominal obesity [8 with normal glucose tolerance (oNGT), 8 with impaired glucose tolerance (oIGT)] and 8 normal-weight subjects matched for age, sex and blood pressure. In oNGT and oIGT, fasting plasma C-peptide levels were twice those in the controls (962 +/- 51 and 915 +/- 85 vs 439 +/- 28 pmol/l, P < 0.001) and their suppression was lower than in the controls, both in absolute terms (155 +/- 19 and 185 +/- 17 vs 274 +/- 18 pmol/l, P < 0.001) and as a percentage decline from basal levels (16 +/- 2% and 21 +/- 2% vs 63 +/- 2%, P < 0.001). Fasting plasma glucagon levels were similar in the patients and in the controls, but were less suppressed during clamp in oNGT and oIGT, both in absolute terms (7.0 +/- 0.9 and 5.6 +/- 0.6 vs 13.2 +/- 1.2 pmol/l, P < 0.001) and as a percentage change from basal levels (23 +/- 3% and 19 +/- 2% vs 44 +/- 4%, P < 0.001). These results suggest that the insulin feedback on B and A cells is impaired in abdominal obesity, and that this defect is of similar degree in oNGT and oIGT. These alterations could be implicated in the pathogenesis of hyperinsulinemia in obesity.