ArticleJournal of translational autoimmunity2021
Proinsulin:C-peptide ratio trajectories over time in relatives at increased risk of progression to type 1 diabetes.
Article in Journal of translational autoimmunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The trial behind it
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Article
- Genetic Predictors of Response to Oral Insulin for Type 1 Diabetes Prevention.Diabetes care · 2026Article
- Stress-driven remodeling of antigen presentation and chemokine signaling in pancreatic β-cells: implications for type 1 diabetes.Frontiers in immunology · 2026Review
- Insulin Secretion and Insulin Sensitivity Change in Different Stages of Adult-Onset Type 1 Diabetes: A Cross-Sectional Study.Journal of clinical medicine · 2025Article
- The beta cell-immune cell interface in type 1 diabetes (T1D).Molecular metabolism · 2023Review
- Quantifying beta cell function in the preclinical stages of type 1 diabetes.Diabetologia · 2023Review
- C-peptide determination in the diagnosis of type of diabetes and its management: A clinical perspective.Diabetes, obesity & metabolism · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveBiomarkers are needed to characterize heterogeneity within populations at risk for type 1 diabetes. The ratio of proinsulin to C-peptide (PI:C ratio), has been proposed as a biomarker of beta cell dysfunction and is associated with progression to type 1 diabetes. However, relationships between PI:C ratios and autoantibody type and number have not been examined. We sought to characterize PI:C ratios in multiple islet autoantibody positive, single autoantibody positive and autoantibody negative relatives of individuals with type 1 diabetes.
methodsWe measured PI:C ratios and autoantibodies with both electrochemiluminescence (ECL) assays (ECL-IAA, ECL-GADA and ECL-IA2A) and radiobinding (RBA) assays (mIAA, GADA, IA2A and ZnT8A) in 98 relatives of individuals with type 1 diabetes followed in the TrialNet Pathway to Prevention Study at the Barbara Davis Center for a mean of 7.4 ± 4.1 years. Of these subjects, eight progressed to T1D, 31 were multiple autoantibody (Ab) positive, 37 were single Ab positive and 22 were Ab negative (by RBA).
resultsIn cross-sectional analyses, there were no significant differences in PI:C ratios between type 1 diabetes and/or multiple Ab positive subjects (4.16 ± 4.06) compared to single Ab positive subjects (4.08 ± 4.34) and negative Ab subjects (3.72 ± 3.78) (p = 0.92) overall or after adjusting for age, sex and BMI. Higher PI:C ratios were associated with mIAA titers (p = 0.03) and showed an association with ECL-IA2A titers (p = 0.09), but not with ECL-IAA, GADA, ECL-GADA, IA2A nor ZnT8A titers. In mixed-effects longitudinal models, the trajectories of PI:C ratio over time were significantly different between the Ab negative and multiple Ab positive/type 1 diabetes groups, after adjusting for sex, age, and BMI (p = 0.04).
conclusionsPI:C ratio trajectories increase over time in subjects who have multiple Ab or develop type 1 diabetes and may be a helpful biomarker to further characterize and stratify risk of progression to type 1 diabetes over time.
Identifiers
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Registered trials
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