The course and determinants of insulin action in Type 1 (insulin-dependent) diabetes mellitus

The course and determinants of insulin action were investigated in 8 newly diagnosed Type 1 (insulin-dependent) diabetic patients, who were studied every 3 months for one year, and in three groups of 8 patients each with 5, 10 and 20 years diabetes, studied once. Fifteen healthy subjects matched for age, sex and body weight served as control subjects. Dose-response curves were constructed using sequential euglycaemic (5.0 mmol/l) clamps (insulin infusion rates: 0.5, 1.0, 2.0 and 5.0 mU.kg-1.min-1 in periods of 2h). After 1/2 month of insulin treatment, insulin responsiveness was normal, but sensitivity was decreased (ED50 70 +/- 7 mU/l (SEM) vs 54 +/- 4 mU/l in control subjects, p less than 0.05). After 6 months, insulin sensitivity was improved (ED50 57 +/- 4 mU/l, p less than 0.01 vs 1/2 month and not significant (NS) vs control subjects); but after 9 and 12 months, it was reduced again, similarly to 0.5 month. Insulin responsiveness remained normal at all time-points. In the three groups of patients with longstanding diabetes, impaired insulin sensitivity with normal responsiveness was noted also (ED50 73 +/- 9 mU/l, p less than 0.02 vs control subjects). At 6, 9 and 12 months, glycaemic control (HbA1) and insulin dose were inverse correlates for insulin action; in patients with longstanding disease, this was noted for HbA1 and body weight, in control subjects for body weight. In conclusion, decreased insulin sensitivity re-develops in Type 1 diabetes within the first year following an initial improvement.