Effects of Exenatide Alone and in Combination With Daclizumab on β-Cell Function in Long-Standing Type 1 Diabetes

OBJECTIVE - in patients with long-standing type 1 diabetes, we investigated whether improved P-cell function can be achieved by combining intensive insulin therapy with agents that may 1) promote beta-cell growth and/or limit beta-cell apoptosis and 2) weaken the anti-beta-cell autoimmunity. RESEARCH DESIGN AND METHODS - For this Study, 20 individuals (mean age 39.5 +/- 11.1. years) with long-standing type I diabetes (21.3 +/- 10.7 years) were enrolled in this prospective open-label crossover trial. After achieving optimal blood glucose control, 16 subjects were randomized to exenatide with or Without daclizumab. Endogenous insulin production was determined by repeatedly measuring serum C-peptide. RESULTS - In 85% of individuals with long-standing type 1. diabetes who were screened for participation in this trial, C-peptide levels >= 0.05 ng/ml (0.02 nmol/1) were found. Residual P-cells responded to physiological (mixed-meal) and pharmacological (arginine) stimuli. During exenatde treatment, patients lost 4.1 +/- 2.9 kg body wt and insulin requirements declined significantly (total daily close on exenatide 0.48 +/- 0.11 Vs. 0.55 +/- 0.13 units . kg(-1) . day(-1) without exenatide; P = 0.0062). No signs of further activation of the underlying autoimmune disease were observed. Exenatide delayed gastric emptying, suppressed endogenous incretin levels, but did not increase C-peptide secretion. CONCLUSIONS - In long-standing type 1. diabetes, which remains an active autoimmune disease even decades after its onset, surviving beta-cells Secrete insulin in a physiologically regulated manner. However, the combination of intensified insulin therapy, exenatide, and daclizumab did not induce improved function of these remaining beta-cells.