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

Oleh:

Rother, Kristina I. ; Spain, Lisa M. ; Wesley, Robert A. ; Digon, Benigno J. III ; Baron, Alain

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Diabetes Care vol. 32 no. 12 (Dec. 2009), page 2251-2257.

Ketersediaan

Perpustakaan FK Nomor Panggil: D05.K.2009.03 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

OBJECTIVE In patients with long-standing type 1 diabetes, we investigated whether improved ß-cell function can be achieved by combining intensive insulin therapy with agents that may 1) promote ß-cell growth and/or limit ß-cell apoptosis and 2) weaken the anti–ß-cell autoimmunity. RESEARCH DESIGN AND METHODS For this study, 20 individuals (mean age 39.5 ± 11.1 years) with long-standing type 1 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/l) were found. Residual ß-cells responded to physiological (mixed-meal) and pharmacological (arginine) stimuli. During exenatide treatment, patients lost 4.1 ± 2.9 kg body wt and insulin requirements declined significantly (total daily dose 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 ß-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 ß-cells.

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