Continuous subcutaneous insulin infusion fails to correct impaired basal glucose metabolism and impaired insulin sensitivity of adipocytes from patients with type 1 (insulin-dependent) diabetes

Abstract

Studies of the in vivo insulin action in conventionally treated Type 1 diabetic patients have shown insulin resistance, especially in poorly controlled patients. We reported previously on impaired basal and insulin-stimulated glucose utilization in adipocytes from Type 1 diabetic subjects. In this study we have examined whether a near-normalization of glycaemia and plasma levels of metabolites in Type 1 diabetic patients induced by continuous subcutaneous insulin infusion might reverse abnormalities of adipose tissue metabolism. 11 Type 1 diabetic subjects who had been treated conventionally with diet and insulin for 11 yr were studied before and after continuous subcutaneous insulin infusion for 6 months. In Type 1 diabetic patients before insulin pump treatment we found decreased adipocyte insulin binding (p less than 0.01), normal insulin binding to monocytes and erythrocytes, impaired insulin sensitivity of the adipocyte glucose transport (p = 0.02) and reduced basal and maximally insulin-stimulated rates of adipocyte glucose oxidation and lipogenesis (all p less than 0.05). After pump therapy for 6 months we found a further reduction of basal and maximal adipocyte glucose oxidation and lipogenesis (all p less than or equal to 0.05), whereas we found no significant changes of insulin receptor binding or insulin sensitivity of adipocyte glucose utilization. We conclude that continuous subcutaneous insulin infusion of Type 1 diabetic patients for 6 months aggravates the defects in basal (non-insulin-stimulated) and maximally insulin-stimulated glucose utilization of isolated adipocytes despite an optimization of glycaemic control and a near-normalization of plasma metabolites.