Improved Insulin Sensitivity in Patients with Type I Diabetes Mellitus After CSII

Tissue sensitivity to insulin was studied using the euglycemic insulin clamp technique (delta plasma insulin above basal 90 microU/ml) in eight patients with type I diabetes mellitus (IDDM) before and after 4-8 mo of continuous subcutaneous insulin infusion (CSII) and in 36 age-matched control subjects. Institution of CSII was associated with significant improvements in glycosylated hemoglobin (HbA1) (11.2 +/- 0.6% versus 8.1 +/- 0.4%; P less than 0.001) and mean 24-h plasma glucose concentrations (239 +/- 23 mg/dl versus 106 +/- 18 mg/dl; P less than 0.001). Insulin-mediated glucose metabolism in the diabetic patients pre-CSII (3.92 +/- 0.36 mg/kg X min) was reduced by 44% compared with controls (7.03 +/- 0.22 mg/kg X min; P less than 0.001). After 4-8 mo of improved glycemic control, improved tissue sensitivity to insulin was observed (5.33 +/- 0.75 mg/kg X min; P less than 0.05 versus pre-CSII). However, insulin-mediated glucose utilization still remained significantly below control values (P less than 0.01). During hyperinsulinemia, hepatic glucose production (3-3H-glucose) was suppressed by over 90% in diabetic patients (pre- and post-CSII) and in control subjects. We conclude that near-normalization of glucose metabolism with CSII partially corrects, but does not restore to normal, insulin-stimulated glucose uptake in IDDM. Our failure to totally reverse the impaired response of peripheral tissues to insulin in IDDM patients may be attributed to inadequate metabolic correction, the peripheral route of insulin administration, or a primary defect in glucose metabolism.