Hormonal and metabolic counterregulation during and after high-dose insulin-induced hypoglycemia in diabetes mellitus type 2

Non-obese type 2 diabetic subjects in good metabolic control (n = 6, HbA(1c) 7.0 +/- 0.3%, mean diabetes duration: 5.7 +/- 1 years) and matched non-diabetic subjects (control; n = 6) were studied during hyperinsulinemic (similar to3 nmol/l)-hypoglycemic (similar to3.1 mmol/l) clamp tests (0-120 min) and the subsequent recovery period (120-240 min). Plasma glucagon rose gradually but not significantly, whereas norepinephrine and epinephrine similarly increased similar to2 and similar to 25-fold in both groups. Islet amyloid polypeptide (IAPP) decreased to similar to 41% and similar to 24% of basal values during hypoglycemia and rapidly rose similar to4.7-fold during the recovery period, while plasma C-peptide remained suppressed in both groups. Within 140 min, plasma free fatty acids similarly decreased to similar to 70 mu mol/l (p < 0.05), but then rose to values being <similar to>50% higher in diabetic than in control subjects (240 min: 907 +/- 93 vs. 602 +/- 90 mu mol/l; p < 0.05). Glucose infusion rates were comparable during hypoglycemia, but <similar to>40% lower during ;recovery in diabetic patients (1.88 +/- 0.27 vs. 3.44 +/- 0.27 mg.kg(-1).min(-1), p < 0.001). These results demonstrate that (i) hypoglycemia induced by high-dose insulin largely abolishes the counterregulatory response of glucagon, but not of catecholamines in nondiabetic and well-controlled type 2 diabetic subjects, (ii) the rapid posthypoglycemic increase of plasma IAPP occurs independently of plasma insulin, and (iii) the superior rise in plasma free fatty acids may account at least in part for the posthypoglycemic insulin resistance of type 2 diabetic patients.