C-peptide levels in subjects followed longitudinally before and after type 1 diabetes diagnosis in TrialNet
Open accessAbstract
OBJECTIVE: Insulin secretion declines rapidly after diagnosis of type 1 diabetes, followed by a slower rate of change. Previous studies have demonstrated that the C-peptide decline begins before the clinical diagnosis. Changes in insulin secretion in the same individuals studied from preclinical stages through and after clinical diagnosis have not been previously reported. RESEARCH DESIGN AND METHODS: Antibody-positive relatives undergo sequential oral glucose tolerance testing (OGTT) as part of TrialNet's Pathway to Prevention study and continue both OGTT and mixed-meal tolerance testing (MMTT) as part of the Long-term Investigational Follow-up in TrialNet study if they develop type 1 diabetes. We analyzed glucose and C-peptide data obtained from 80 TrialNet subjects who had OGTT before and after clinical diagnosis. Separately, we compared C-peptide response to OGTT and MMTT in 127 participants after diagnosis. RESULTS: C-peptide did not change significantly until 6 months before the clinical diagnosis of type 1 diabetes and continued to decline postdiagnosis, and the rates of decline for the first 6 months postdiagnosis were similar to the 6 months prediagnosis. There were no significant differences in MMTT and OGTT C-peptide responses in paired tests postdiagnosis. CONCLUSIONS: This is the first analysis of C-peptide levels in longitudinally monitored patients with type 1 diabetes studied from before diagnosis and continuing to the postdiagnosis period. These data highlight the discordant timing between accelerated β-cell dysfunction and the current glucose thresholds for clinical diagnosis. To preserve β-cell function, disease-modifying therapy should start at or before the acute decline in C-peptide.
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The rate of β-cell destruction is quite variable, being rapid in some individuals and slow in others.
“The rate of b -cell destruction is quite variable, being rapid in some individuals (particularly but not exclusively in infants and children) and slow in others (mainly but not exclusively adults) (46,59).”
From 2. Diagnosis and Classification of Diabetes: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [46]
The Introduction (page unavailable) says adults have a slower rate of C-peptide decline than children, and the Results (page unavailable) find that age influences that rate. This supports an age-related difference in β-cell function, but the paper measures C-peptide rather than the rate of β-cell destruction and does not establish the claim specifically for infants. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGlucose and A1C levels may rise well before the clinical onset of diabetes; changes in FPG and 2-h PG can occur about 6 months before diagnosis.
“Glucose and A1C levels may rise well before the clinical onset of diabetes (e.g., changes in FPG and 2-h PG can occur about 6 months before diagnosis) (46), making diagnosis feasible well before the onset of DKA.”
From 2. Diagnosis and Classification of Diabetes: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [46]
The Results (page unavailable) report that mean fasting and 2-hour glucose levels began increasing about six months before type 1 diabetes diagnosis, supporting the FPG and 2-h PG example. The paper does not report a corresponding prediagnosis rise in A1C; searches for A1C and HbA1c found no such passage. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe rate of b-cell destruction is quite variable, being rapid in some individuals (particularly but not exclusively in infants and children) and slow in others (mainly but not exclusively adults).
“The rate of b-cell destruction is quite variable, being rapid in some individuals (particularly but not exclusively in infants and children) and slow in others (mainly but not exclusively adults) (44,58).”
From 2. Diagnosis and classification of diabetes: standards of care in diabetes-2025 (2025) · cites this paper as [44]
The Introduction (page unavailable) reports that adults have a slower rate of C-peptide decline than children, and the Results find that age influences that rate. This supports the age-related pattern, but the paper measures C-peptide as an indicator of β-cell function, not the rate of β-cell destruction, and its participants were aged 3.9 years or older, so it does not establish the claim about infants. (LLM, conf=0.85)
Experimental — accuracy not yet measuredGlucose and A1C levels may rise well before the clinical onset of diabetes (e.g., changes in FPG and 2-h PG can occur about 6 months before diagnosis).
“Glucose and A1C levels may rise well before the clinical onset of diabetes (e.g., changes in FPG and 2-h PG can occur about 6 months before diagnosis) (44), making diagnosis feasible under ideal situations of serial monitoring of individuals at high risk of type 1 diabetes before the onset of DKA.”
From 2. Diagnosis and classification of diabetes: standards of care in diabetes-2025 (2025) · cites this paper as [44]
The Results report that mean fasting and 2-hour glucose levels began rising about six months before clinical type 1 diabetes diagnosis, supporting the glucose portion of the claim. Our copy does not report a prediagnosis rise in A1C (searched: A1C, HbA1c), so that part is unsupported. (LLM, conf=0.89)
Experimental — accuracy not yet measured
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- Authors
- Bogun, M. M., Bundy, B. N., Goland, R. S., & Greenbaum, C. J.
- Affiliations
- Columbia University (US)
- University of South Florida (US)
- Benaroya Research Institute (US)
- Corresponding author
- Bogun, Magdalena M.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2020-05-26
- Volume
- 43
- Issue
- 8
- Pages
- 1836-1842
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC7372058
- OpenAlex
- W3029699951
- Cited by
- 72
- References
- 28
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 13 · 2023: 15 · 2022: 10 · 2021: 13 · 2020: 3
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health Clinical Center (U01-DK-061010, U01-DK-061034, U01-DK-061042, U01-DK-061058)
- JDRF
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 1 diabetes, C-peptide, insulin secretion, beta-cell dysfunction, preclinical type 1 diabetes, disease-modifying therapy, diagnosis, mixed meal tolerance test, oral glucose tolerance test, TrialNet
- MeSH terms
- Insulin Secretion, Adolescent, Adult, Blood Glucose, C-Peptide, Child, Child, Preschool, Diabetes Mellitus, Type 1, Diagnostic Techniques, Endocrine, Female, Follow-Up Studies, Glucose Tolerance Test, Humans, Longitudinal Studies, Male, Middle Aged, Monitoring, Physiologic, Cohort Studies, Disease Progression, Young Adult, Meals
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