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Cited by 131Diabetes Management and ResearchDiabetes and associated disordersPancreatic function and diabetes

Low levels of C‐peptide have clinical significance for established Type 1 diabetes

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Kuhtreiber, W. M., Washer, S. L. L., Hsu, E., Zhao, M., Reinhold, P., Burger, D., Zheng, H., Faustman, D. L.·2015·Diabetic Medicine
DOI 10.1111/dme.12850PMC PMC4578991
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Abstract

Aim: To determine whether the low C‐peptide levels (< 50 pmol/l) produced by the pancreas for decades after onset of Type 1 diabetes have clinical significance. Methods: We evaluated fasting C‐peptide levels, duration of disease and age of onset in a large cross‐sectional series ( n = 1272) of people with Type 1 diabetes. We then expanded the scope of the study to include the relationship between C‐peptide and HbA 1c control ( n = 1273), as well as diabetic complications ( n = 324) and presence of hypoglycaemia ( n = 323). The full range of C‐peptide levels was also compared with 1,5‐Anhydroglucitol, a glucose responsive marker. Results: C‐peptide levels declined for decades after diagnosis, and the rate of decline was significantly related to age of onset ( P < 0.0001), after adjusting for disease duration. C‐peptide levels > 10 pmol/l were associated with protection from complications (e.g. nephropathy, neuropathy, foot ulcers and retinopathy; P = 0.03). Low C‐peptide levels were associated with poor metabolic control measured by HbA 1c ( P < 0.0001). Severe hypoglycaemia was associated with the lowest C‐peptide levels compared with mild ( P = 0.049) or moderate ( P = 0.04) hypoglycaemia. All levels of measurable C‐peptide were responsive to acute fluctuations in blood glucose levels as assessed by 1,5‐Anhydroglucitol ( P < 0.0001). Conclusions: Low C‐peptide levels have clinical significance and appear helpful in characterizing groups at‐risk for faster C‐peptide decline, complications, poorer metabolic control and severe hypoglycaemia. Low C‐peptide levels may be a biomarker for characterizing at‐risk patients with Type 1 diabetes.

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  • Levels of C-peptide can be useful in distinguishing diabetes mellitus type and guiding treatment.

    “Although levels of C-peptide can be useful in distinguishing diabetes mellitus type and guiding treatment, which is the ultimate purpose of classification, C-peptide assays are expensive and difficult to perform, limiting their utility outside high-income settings92.”

    From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [92]

    The Introduction (page unavailable) says biomarkers predicting vulnerability to complications might enable targeted therapeutic strategies, and the Abstract Conclusions describe C-peptide as a possible marker of at-risk patients with established Type 1 diabetes. This supports a potential role in guiding care, but the study includes only people already classified as having Type 1 diabetes and does not show that C-peptide distinguishes diabetes types. (LLM, conf=0.84)

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  • C-peptide assays are expensive and difficult to perform, limiting their utility outside high-income settings.

    “Although levels of C-peptide can be useful in distinguishing diabetes mellitus type and guiding treatment, which is the ultimate purpose of classification, C-peptide assays are expensive and difficult to perform, limiting their utility outside high-income settings92.”

    From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [92]

    The Patients and methods section describes the C-peptide assays used but does not discuss their cost, difficulty, or availability by setting. The Discussion calls a decades-long longitudinal study expensive to perform—not the assays themselves. Searches for assay cost and access outside high-income settings found no supporting passage in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Authors
Kuhtreiber, W. M., Washer, S. L. L., Hsu, E., Zhao, M., Reinhold, P., Burger, D., Zheng, H., & Faustman, D. L.
Affiliations
  • Immunobiology Laboratory Harvard Medical School and Massachusetts General Hospital Boston MA USA
  • Harvard University (US)
  • Massachusetts General Hospital (US)
Corresponding author
Faustman, D. L.
ORCID
Venue
Diabetic Medicine
Publisher
Wiley
Published
2015-08-16
Volume
32
Issue
10
Pages
1346-1353
ISSN
  • 0742-3071 (ISSN-L)
  • 1464-5491
DOI
10.1111/dme.12850
PMC
PMC4578991
OpenAlex
W2108678942
Cited by
131
References
1
Citations by year
2026: 3 · 2025: 7 · 2024: 11 · 2023: 16 · 2022: 17 · 2021: 13 · 2020: 22 · 2019: 10 · 2018: 7 · 2017: 11 · 2016: 9 · 2015: 5
FWCI
9.25
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Diabetic Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • The Iacocca Foundation
  • NIH BADRC (P30 DK057521)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
C-peptide, type 1 diabetes, beta-cell function, age of onset, disease duration, HbA1c, glycemic control, diabetes complications, kidney disease, neuropathy, retinopathy, hypoglycemia, 1,5-anhydroglucitol, glucose responsiveness, biomarkers
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Blood Glucose, C-Peptide, Child, Cross-Sectional Studies, Deoxyglucose, Diabetes Mellitus, Type 1, Glycated Hemoglobin, Humans, Middle Aged, Prognosis, Young Adult

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