Effect of dietary energy restriction on glucose production and substrate utilization in type 2 diabetes

A total of 8 obese subjects with type 2 diabetes were studied while on a eu caloric diet and after reduced energy intake (25 and then 75% of requiremen ts for 10 days each). Weight loss was 2, 3, and 3 kg after 5, 10, and 20 da ys, respectively; all of the weight lost was body fat. Fasting blood glucos e (FBG) levels fell from 11.9 +/- 1.4 at baseline to 8.9 +/- 1.6, 7.9 +/- 1 .4, and 8.8 +/- 1.3 mmol/l at days 5, 10, and 20, respectively (P < 0.05, b aseline vs. 5, 10, and 20 days). Endogenous glucose production (EGP) was 22 +/- 2, 18 +/- 2, 17 +/- 2, and 22 +/- 2 pmol kg-(1) lean body mass (LBM) m in(-1) (P < 0.05, days 5 and 10 vs. baseline). Gluconeogenesis measured by mass isotopomer distribution analysis provided 31 +/- 4, 41 +/- 5, 40 +/- 4 , and 33 +/- 4%, respectively, of the EGP (NS); absolute glycogenolytic con tribution to the EGP was 15 +/- 2, 11 +/- 2, 11 +/- 2, and 15 +/- 2 mu mol kg(-1) LBM. min(-1), respectively (P < 0.001, baseline vs. days 5 and 10 an d day 10 vs, day 20). The blood glucose clearance rate increased significan tly at day 20 (P < 0.05). Neither lipolysis nor flux of plasma nonesterifie d fatty acids were altered compared with baseline. In conclusion, severe en ergy restriction per se independent of major changes in body composition re duces both FBG concentration and EGP in type 2 diabetes, the reduction in E GP results entirely from a reduction of glycogenolytic input into blood glu cose, and the duration of reduced glycogenolysis is short-lived after relax ation of energy restriction even without weight gain, but effects on plasma glucose clearance persist and partially maintain the improvement in fastin g glycemia.