Effects of hypocaloric diet and insulin therapy on metabolic control and mechanisms of hyperglycemia in obese non-insulin-dependent diabetic subjects

Abstract

We studied the effects of hypocaloric diet (500 kcal/d) and insulin therapy in 15 obese (body mass index >30.0 kg/m 2) non-insulin-dependent diabetic patients with secondary drug failure and poor metabolic control. The patients were randomly allocated either to hypocaloric diet (n = 8) or to insulin treatment (n = 7). After 2 weeks of treatment there was a significant improvement in the fasting blood glucose, in the mean diurnal glucose, in glucosuria, and in glucose response to a 75-g oral glucose load in both groups. No change in insulin secretion was seen in either group. Glucose disposal rates (GDR) improved significantly both in the diet-treated group (from 2.34 ± 0.15 to 4.01 ± 0.40 mg/kg/min, P < .01) and in the insulin-treated group (from 2.46 ± 0.33 to 2.77 ± 0.29 mg/kg/min, P < .01). The improvement was greater in the diet-treated group (71%) than in the insulin-treated group (13%, P < .05). The increase of GDR in the diet-treated group was due to an increase of nonoxidative GDR (from 1.18 ± 0.17 to 2.98 ± 0.39 mg/kg/min, P < .001) as assessed by indirect calorimetry. In the insulin-treated group there was a small increase both in oxidative and nonoxidative GDR, but the changes were not statistically significant. Hepatic glucose output (HGO) in a postabsorptive state decreased significantly both in the diet-treated group (from 2.49 ± 0.15 to 2.04 ± 0.10 mg/kg/min, P < .01) and in the insulin-treated group (from 2.63 ± 0.23 to 2.05 ± 0.12 mg/kg/min, P < .01). We made the following conclusions: (1) Treatment with hypocaloric diet (and weight loss) or insulin improved metabolic control in obese non-insulin-dependent diabetic subjects with secondary drug failure. (2) The improvement in metabolic control was due mainly to increased GDR in the diet-treated group and to reduced basal HGO in the insulin-treated group. (3) The nonoxidative GDR increased in the diet-treated group but not in the insulin-treated group. (4) No improvement in insulin secretion capacity was seen either in the diet-treated group or in the insulin-treated group.