Regulation of endogenous glucose production after a mixed meal in type 2 diabetes

Abstract

The extent and time course of suppression of endogenous glucose production (EGP) in type 2 diabetes after a mixed meal have been determined using a new tracer methodology. Groups of age-, sex-, and weight-matched normal controls ( n = 8) and diet-controlled type 2 diabetic subjects ( n = 8) were studied after ingesting a standard mixed meal (550 kcal; 67% carbohydrate, 19% fat, 14% protein). There was an early insulin increment in both groups such that, by 20 min, plasma insulin levels were 266 ± 54 and 190 ± 53 pmol/l, respectively. EGP was similar basally [2.55 ± 0.12 mg · kg−1 · min−1 in control subjects vs. 2.92 ± 0.16 mg · kg−1 · min−1 in the patients ( P = 0.09)]. After glucose ingestion, EGP declined rapidly in both groups to ∼50% of basal within 30 min of the meal. Despite the initial rapid decrease, the EGP was significantly greater in the diabetic group at 60 min (1.75 ± 0.12 vs. 1.05 ± 0.14 mg · kg−1 · min−1; P < 0.01) and did not reach nadir until 210 min (0.96 ± 0.17 mg · kg−1 · min−1). Between 60 and 240 min, EGP was 47% higher in the diabetic group (0.89 ± 0.09 vs. 1.31 ± 0.13 mg · kg−1 · min−1, P < 0.02). These data quantitate the initial rapid suppression of EGP after a mixed meal in type 2 diabetes and the contribution of continuing excess glucose production to subsequent hyperglycemia.