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.