In vivo insulin action and muscle glycogen synthase activity in Type 2 (non-insulin-dependent) diabetes mellitus: effects of diet treatment

Insulin resistant glucose metabolism is a key element in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus. Insulin resistance may be of both primary (genetic) and secondary (metabolic) origin. Before and after diet-induced improvement of glycaemic control seven obese patients with newly-diagnosed Type 2 diabetes were studied with the euglycaemic clamp technique in combination with indirect calorimetry and forearm glucose balance. Muscle biopsies were obtained in the basal state and again after 3 h of hyperinsulinaemia (200 mU/l) for studies of insulin receptor and glycogen synthase activities. Similar studies were performed in seven matched control subjects. Insulin-stimulated glucose utilization improved from 110 +/- 11 to 183 +/- 23 mg.m-2.min-1 (p less than 0.03); control subjects: 219 +/- 23 mg.m-2.min-1 (p = NS, vs post-diet Type 2 diabetes). Non-oxidative glucose disposal increased from 74 +/- 17 to 138 +/- 19 mg.m-2.min-1 (p less than 0.03), control subjects: 159 +/- 22 mg.m-2.min-1 (p = NS, vs post-diet Type 2 diabetic patients). Forearm blood glucose uptake during hyperinsulinaemia increased from 1.58 +/- 0.54 to 3.35 +/- 0.23 mumol.l-1.min-1 (p less than 0.05), control subjects: 2.99 +/- 0.86 mumol.l-1.min-1 (p = NS, vs post-diet Type 2 diabetes). After diet therapy the increase in insulin sensitivity correlated with reductions in fasting plasma glucose levels (r = 0.97, p less than 0.001), reductions in serum fructosamine (r = 0.77, p less than 0.05), and weight loss (r = 0.78, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)