Effects of exenatide alone and in combination with daclizumab on β-cell function in long-standing type 1 diabetes
Open accessAbstract
OBJECTIVE: In patients with long-standing type 1 diabetes, we investigated whether improved β-cell function can be achieved by combining intensive insulin therapy with agents that may 1) promote β-cell growth and/or limit β-cell apoptosis and 2) weaken the anti–β-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 β-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 β-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 β-cells.
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When sensitive C-peptide measurements are performed, 30-80% of people with long-term type 1 diabetes are found to be insulin microsecretors.
“When sensitive C-peptide measure ments are performed, 30–80% of people with long-term type 1 diabetes are found to be insulin microsecretors.64–67”
From Type 1 diabetes (2018) · cites this paper as [67]
The Results (C-peptide secretion) report detectable C-peptide in 85% of 40 screened participants with long-standing type 1 diabetes, using an assay with a detection limit of 0.05 ng/ml (Methods, Assays). This supports the point that sensitive testing finds residual insulin secretion, but this paper reports 85%, not the claimed 30–80% range. (LLM, conf=0.87)
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“25,26 30 In all studies, placebo-corrected reductions of body weight from 4.3 to 6.8 kg, and in total daily insulin dose of between 5 and 10 U/day, have been found for liraglutide 1.8-mg OD.”
Influential
- Authors
- Rother, K. I., Spain, L. M., Wesley, R. A., Digon, B. J., Baron, A., Chen, K., Nelson, P., Dosch, H.-M., Palmer, J. P., Brooks-Worrell, B., Ring, M., & Harlan, D. M.
- Affiliations
- National Institutes of Health (US)
- Amylin Pharmaceuticals, San Diego, California;
- Hospital for Sick Children (CA)
- University of Washington (US)
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington.
- Corresponding author
- Rother, Kristina I.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2009-10-06
- Volume
- 32
- Issue
- 12
- Pages
- 2251-2257
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC2782986
- OpenAlex
- W2061627213
- Cited by
- 133
- References
- 26
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 1 · 2021: 3 · 2020: 8 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 11 · 2015: 10 · 2014: 7 · 2013: 17 · 2012: 7
- FWCI
- 8.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Amylin Pharmaceuticals
- National Institutes of Health (Z99 DK999999)
- National Institute of Diabetes and Digestive and Kidney Diseases (ZIADK055104)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- exenatide, daclizumab, type 1 diabetes, beta-cell function, residual beta-cell function, C-peptide, intensive insulin therapy, incretin-based therapy, beta-cell apoptosis, insulin requirement, gastric emptying, arginine stimulation, mixed meal tolerance
- MeSH terms
- Exenatide, Daclizumab, Adult, Antibodies, Monoclonal, Diabetes Mellitus, Type 1, Drug Therapy, Combination, Female, Glycated Hemoglobin, HLA-DR Antigens, Humans, Hypoglycemic Agents, Immunoglobulin G, Immunosuppressive Agents, Insulin, Male, Peptides, Surveys and Questionnaires, Research Design, United States, Venoms, Autoimmunity, Age of Onset, Cross-Over Studies, Insulin-Secreting Cells, Young Adult, HLA-DRB1 Chains, Antibodies, Monoclonal, Humanized
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