High-Dose Intravenous Insulin Infusion Versus Intensive Insulin Treatment in Newly Diagnosed IDDM

Abstract

High-dose intravenous insulin infusion at the onset of IDDM has been suggested to improve β-cell function during the 1st year of insulin treatment. To test this hypothesis, we randomly assigned newly diagnosed IDDM patients to receive either an experimental 2-week high-dose intravenous insulin infusion (n = 9; age, 25 ± 7 years; HbA_1c, 10.5 ± 2.0%) or an intensive insulin therapy of four injections per day (n = 10; age, 28 ± 7 years; HbA_1c, 12.3 ± 3.0%). The experimental-therapy group received three times more insulin (1.2 ± 0.4 U · kg⁻¹ · day⁻¹) than the intensive-therapy group (0.4 ± 0.1 U · kg⁻¹ · day⁻¹, P < 0.0005). By week 3, both groups were treated similarly with intensive insulin therapy and were followed for 1 year, β-cell function was evaluated with fasting plasma C-peptide and glucagon-stimulated and mixed meal-stimulated C-peptide concentrations. In both groups, insulin doses were comparable, and HbA_1c levels were near normal during follow-up. At diagnosis of IDDM, fasting C-peptide was 0.40 ± 0.13 nmol/l in the experimental-therapy group and 0.39 ± 0.23 nmol/1 in the intensive-therapy group. Irrespective of treatment, a slight decline of fasting C-peptide was observed in sequential measurements up to 12 months in both groups (Δ, -0.13 and -0.08 nmol/1, respectively; NS). Glucagon-stimulated C-peptide concentrations decreased from 0.54 ± 0.18 and 0.70 ± 0.39 nmol/l at month 0 to 0.41 ± 0.20 and 0.61 ± 0.52 nmol/1, respectively, at month 12. In the experimental-therapy group, mixed meal-stimulated C-peptide concentrations (area under the curve over 2 h) increased from 82.10 ± 43.72 to 101.20 ± 32.53 nmol/L and in the intensive-therapy group, from 75.05 ± 46.01 to 107.20 ± 102.51 nmol/1. Changes in stimulated C-peptide concentrations between month 0 and 12 were not significant in both groups. During follow-up, fasting and stimulated C-peptide concentrations were not significantly different between the experimental-therapy group and the intensive-therapy group. We conclude that as initial treatments of newly diagnosed IDDM, high-dose intravenous insulin infusion and intensive insulin therapy equally preserve β-cell function during the 1st year of insulin therapy.