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-di abetic subjects (control; n = 6) were studied during hyperinsulinemic (simi lar 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 gra dually but not significantly, whereas norepinephrine and epinephrine simila rly increased similar to2 and similar to 25-fold in both groups. Islet amyl oid polypeptide (IAPP) decreased to similar to 41% and similar to 24% of ba sal values during hypoglycemia and rapidly rose similar to4.7-fold during t he recovery period, while plasma C-peptide remained suppressed in both grou ps. 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% hi gher 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 hypog lycemia, 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 abo lishes the counterregulatory response of glucagon, but not of catecholamine s in nondiabetic and well-controlled type 2 diabetic subjects, (ii) the rap id 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 dia betic patients.