Insulin resistance in type 1 (insulin-dependent) diabetes: dissimilarities for glucose and intermediary metabolites

To study insulin action on intermediary metabolism in relation to glucose disposal in Type 1 (insulin-dependent) diabetes, 29 patients and 15 control subjects underwent sequential euglycemic clamps (insulin infusion rates 0.5, 1.0, 2.0 and 5.0 mU.kg-1.min-1 in 2 hour periods). Dose-response curves were constructed for insulin-stimulated glucose disposal. Metabolite profiles were determined in the basal state, and during submaximal (+/- 80 mU/l) and maximal (greater than 500 mU/l) insulinaemia. For at least 11 hours preceding the study, blood glucose levels were maintained between 4 and 10 mmol/l in the patients. In the basal state, when at matched glycemia hepatic glucose production is known to be similar in patients and control subjects, glucose, glycerol, free fatty acids and glucagon were comparable, whereas differences were found for alanine (-29%, diabetic vs. control subjects), lactate (-24%), acetoacetate (+270%), 3-hydroxybutyrate (+260%) and insulin (+210%; all p less than 0.02). At submaximal (+/- 80 mU/l) and maximal (greater than 500 mU/l) insulin levels, metabolite levels were comparable, except alanine (-20% diabetic vs. control subjects, p less than 0.001). Glucose disposal rates, however, were decreased in patients at submaximal insulin levels (ED50 73 +/- 10 vs. 54 +/- 4 mU/l in control subjects, p less than 0.01 whereas maximal glucose disposal was similar (61 +/- 3 vs. 65 +/- 3 mumol.kg-1.min-1). In conclusion, in Type 1 diabetes: (a) changes in basal levels of intermediary metabolites were present, despite 11 hours of antecedent euglycemia; (b) in contrast to glucose disposal at submaximal insulinaemia, no major difference existed in insulin's efficacy on intermediary metabolism.