Summary
Hepatic and peripheral insulin sensitivity were investigated in five newly diagnosed Type 1 (insulin-dependent) diabetic subjects before and after 1 week of twice daily insulin therapy. Eight weight-matched control subjects were also studied. Hepatic glucose production and glucose utilization were measured basally and during two sequential 2-h insulin (25 and 40 mU· kg−1· h−1)/glucose infusion periods. In the untreated hyperglycaemic diabetic patients hepatic glucose production was 16.3±2.6, 8.1±1.1 and 3.6±2.8|μmol· kg−1· min−1 respectively for each of the three periods (mean±SEM), and fell with treatment to 12.5±1.4, 0.5±0.5 and 0.5±0.5 μmol· kg−1· min−1. Hepatic glucose production for normal subjects was 13.4±0.7, 2.3±0.8 and <0.1 μmol-kg−1· min−1. Glucose utilization was 12.7±1.4,18.2±0.7 and 22.1±3.4μmol· kg−1· min−1 before treatment in the diabetic subjects, and 11.8±1.7, 20.9±3.3 and 30.1±3.6 after treatment. These values compare with those in the euglycaemic control subjects (13.4±0.7, 18.7±1.6 and 36.3±2.7 μmol · kg−1· min−1). The pre-treatment metabolic clearance rate of glucose in all diabetic studies with insulin levels >30mU/l was 2.6 ±0.4 and rose to 3.9 ±0.5 ml· kg−1· min−1 following insulin therapy. This was significantly lower than in the control subjects (6.7±0.8 ml· kg−1 · min−1; p<0.005). Basal nonesterified fatty acid levels were high in the untreated, but normal in the treated diabetic subjects, and fell in response to insulin infusion. Basal β-hydroxybutyrate levels were high in both diabetic groups, but also fell in response to insulin infusion. Erythrocyte insulin receptor binding was normal in the untreated diabetic subjects, and was not changed by treatment. Therefore, treatment of newly diagnosed Type 1 diabetic subjects with insulin reverses the hepatic insensitivity to insulin. In contrast, treatment only partially improves peripheral glucose disposal. Since erythrocyte insulin receptor binding is normal, it is likely that a post-receptor defect in peripheral glucose metabolism exists in Type 1 diabetic patients despite insulin therapy and good diabetic control for a period of 1 week.
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Nankervis, A., Proietto, J., Aitken, P. et al. Impaired insulin action in newly diagnosed type 1 (insulin-dependent) diabetes mellitus. Diabetologia 27, 497–503 (1984). https://doi.org/10.1007/BF00290383
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DOI: https://doi.org/10.1007/BF00290383