C-Peptide Response and HLA Genotypes in Subjects With Recent-Onset Type 1 Diabetes After Immunotherapy With DiaPep277
Open accessAbstract
OBJECTIVE: To investigate whether lower risk HLA class II genotypes would influence the efficacy of DiaPep277 therapy in protecting β-cell function evaluated by C-peptide secretion in recent-onset type 1 diabetic subjects. RESEARCH DESIGN AND METHODS: Data were collected from type 1 diabetic subjects enrolled in multicenter phase II studies with a randomized, double-blind, and placebo-controlled design in whom fasting and stimulated C-peptide levels were measured. HLA genotypes were classified in high, moderate, and low risk categories. RESULTS: A total of 146 subjects (aged 4.3 to 58.5 years) were enrolled, including 76 children (<18 years old) and 70 adults. At baseline, there was a significant increase in fasting, maximal, and area under the curve (AUC) C-peptide from high to moderate and low risk HLA genotypes in adults (P for trend <0.04) but not in children. Children showed a decrease of the three parameters over time regardless of therapy and HLA genotype. DiaPep277-treated adults with low risk genotype had significantly higher maximal and AUC C-peptide versus placebo at 12 months (0.04 ± 0.07 vs. −0.28 ± 0.09 nmol/L, P < 0.01, and 0.53 ± 1.3 vs. −4.59 ± 1.5 nmol/L, P < 0.05, respectively). In the moderate risk genotype group, Δmaximal and AUC C-peptide values were significantly higher in DiaPep277-treated versus placebo-treated patients (P < 0.01 and P < 0.05, respectively). CONCLUSIONS: This exploratory study demonstrates that type 1 diabetic adults with low and moderate risk HLA genotypes benefit the most from intervention with DiaPep277; the only subgroup with an increase of C-peptide at 12 months after diagnosis was the low risk DiaPep277-treated subgroup.
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Administration of DiaPep277, a synthetic immunomodulator, at 3-month intervals resulted in less of a decline in stimulated C-peptide concentrations at 1 year in adults with type 1 diabetes than in the cohort that received placebo.
“Administration of DiaPep277, a synthetic immunomodulator, at 3-month intervals resulted in less of a decline in stimulated C-peptide concentrations at 1 year in adults with type 1 diabetes than in the cohort that received placebo.142,143”
From Type 1 diabetes (2014) · cites this paper as [142]
The Results report less decline in stimulated C-peptide at 12 months with DiaPep277 than with placebo in adults with moderate-risk HLA genotypes; adults with low-risk genotypes had an increase. The claim omits that genotype qualification. Research Design and Methods also lists dosing at baseline and at 1, 6, and 12 months, not at 3-month intervals. Page numbers are unavailable in our copy. (LLM, conf=0.91)
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Atkinson, M. A., Eisenbarth, G. S., & Michels, A. W. (2014) · The Lancet · doi:10.1016/s0140-6736(13)60591-7 · Cited by 2,713 · see citing works
- Authors
- Buzzetti, R., Cernea, S., Petrone, A., Capizzi, M., Spoletini, M., Zampetti, S., Guglielmi, C., Venditti, C., Pozzilli, P., & on behalf of the DiaPep Trialists Group
- Affiliations
- Sapienza University of Rome (IT)
- Università Campus Bio-Medico (IT)
- Corresponding author
- Buzzetti, Raffaella
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2011-10-17
- Volume
- 60
- Issue
- 11
- Pages
- 3067-3072
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3198071
- OpenAlex
- W2143220398
- Cited by
- 46
- References
- 4
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 8 · 2013: 9 · 2012: 7
- FWCI
- 5.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Weizmann Institute of Science
- Semmelweis Egyetem
- Hebrew University of Jerusalem
- Tel Aviv University
- Debreceni Egyetem
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- type 1 diabetes, recent-onset type 1 diabetes, immunotherapy, C-peptide secretion, beta-cell function, children and adults
- MeSH terms
- Adolescent, Adult, Age Factors, C-Peptide, Child, Child, Preschool, Diabetes Mellitus, Type 1, Double-Blind Method, Female, Genes, MHC Class II, Humans, Hypoglycemic Agents, Immunologic Factors, Kinetics, Male, Middle Aged, Peptide Fragments, Chaperonin 60, Insulin-Secreting Cells, Young Adult, Genetic Association Studies
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