SUPPRESSION OF GLUCONEOGENESIS AFTER A 3-DAY FAST DOES NOT DEPLETE LIVER-GLYCOGEN IN PATIENTS WITH NIDDM

To determine the effect of inhibition of gluconeogenesis on liver glycogen stores in patients with non-insulin-dependent diabetes mellitus (NIDDM) after a 3-day fast, 10% ethanol (EtOH) was administered intravenously to nine obese patients with NIDDM and six obese nondiabetic subjects. Rates of glucose appearance (3-[H-3]glucose) and [U-C-14]alanine incorporation into glucose (alanine gluconeogenesis [Ala-GNG]) were determined before and during EtOH administration, and residual glycogen stores were assessed by the incremental glucose response to glucagon (glucose(AUC)). Hepatic glucose output (HGO) was closely correlated with plasma glucose levels (r = 0.71, P < 0.001) after the 3-day fast and was significantly greater in the diabetic compared with the nondiabetic subjects (13.8 +/- 1.4 vs. 7.6 +/- 0.6 mu mol . kg(-1) FFM . min(-1), P < 0.01). During the 120-min EtOH infusion, Ala-GNG fell by more than 50% in both groups and did not increase after intravenous glucagon administration. HGO fell modestly in both the diabetic and nondiabetic subjects during the first 30 min of EtOH infusion and stabilized thereafter. In contrast to Ala-GNG, HGO increased significantly after intravenous glucagon administration in both the diabetic and nondiabetic subjects, but the increase was significantly greater in the patients with NIDDM (P < 0.01). The glucose area under the curve in response to glucagon (glucose(AUC)) was lower in the presence of EtOH than in its absence (14.9 +/- 7 vs. 68 +/- 15.6 mM/min, P < 0.01) in the obese nondiabetic subjects, which suggests a decrease in liver glycogen stores. In contrast, EtOH Infusion did not alter the glucose(AUC) in obese diabetic subjects compared with saline control studies (134.7 +/- 17.8 vs. 102.6 +/- 20 mM/min, NS). The persistent increase in glucose(AUC) suggests that glycogen stores are not depleted by EtOH-induced suppression of gluconeogenesis in patients with NIDDM after a 3-day fast.