Increased Rate of Cori Cycle in Obese Subjects With NIDDM and Effect of Weight Reduction

To determine the contribution of the rate of glucose recycling via the Cori cycle (glucose→3-carbon compounds→glucose) to the higher rate of endogenous glucose production (EGPR) in subjects with non-insulin-dependent diabetes mellitus (NIDDM), we studied eight obese, weight-stabilized diabetic Pima Indians before [93.1 ± 5.4 kg, 38 ± 2% body fat, fasting plasma glucose (FPG) 254 ± 11 mg/dl] and after (87.7 ± 4.7 kg, 36 ± 2% body fat, FPG 153 ± 17 mg/dl) a 5-wk weight-loss diet and eight obese Indians (95.0 ± 4.2 kg, 36 ± 2% body fat, FPG 97 ± 1 mg/dl) with normal glucose tolerance. EGPR and glucose recycling rate were measured during a 4-h primed continuous tracer infusion of [1-¹³C]glucose, and the rate of reincorporation of 1-¹³C of glucose into C_2–6 positions in glucose was quantified by gas chromatography mass spectrometry. Substrate utilization rates were measured by simultaneous indirect calorimetry. EGPR (corrected for measured rate of recycling) decreased in the diabetic subjects from 3.80 to 2.74 mg·min⁻¹·kg⁻¹ fat-free mass (FFM) (P < .01) after weight loss, approaching the rate observed in nondiabetic subjects (2.09 mg·min⁻¹·kg⁻¹ FFM). The decrease in EGPR was associated with a decrease in nonoxidative carbohydrate disposal. Before weight loss, the measured rate of [1-¹³C]glucose recycling was higher in diabetic (0.23 ± 0.02 mg · min⁻¹ · kg⁻¹ FFM) than in nondiabetic (0.14 ± 0.01 mg min⁻¹ · kg⁻¹ FFM, P < .005) subjects. The glucose recycling rate did not change in diabetic subjects after weight loss (0.20 mg · min⁻¹ · kg⁻¹ FFM). We conclude that the rates of endogenous glucose production and the Cori cycle are increased in subjects with NIDDM compared with the rates observed in obese subjects with normal glucose tolerance. After a modest weight loss, the endogenous glucose production rate, but not the glucose recycling rate, in diabetic subjects approaches the rate observed in obese nondiabetic subjects.