Fall in C-peptide during first 4 years from diagnosis of type 1 diabetes

Variable relation to age, HbA1c, and insulin dose

Wei Hao, Steven Gitelman, Linda DiMeglio, David Boulware, Carla J. Greenbaum

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

OBJECTIVE We aimed to describe the natural history of residual insulin secretion in Type 1 Diabetes TrialNet participants over 4 years from diagnosis and relate this to previously reported alternative clinical measures reflecting β-cell secretory function. RESEARCH DESIGN AND METHODS Data from 407 subjects from 5 TrialNet intervention studies were analyzed. All subjects had baseline stimulated C-peptide values of ≥0.2 nmol/L from mixedmeal tolerance tests (MMTTs). During semiannual visits, C-peptide values from MMTTs, HbA1c, and insulin doses were obtained. RESULTS The percentage of individuals with stimulated C-peptide of ≥0.2 nmol/L or detectable C-peptide of ≥0.017 nmol/L continued to diminish over 4 years; this was markedly influenced by age. At 4 years, only 5% maintained their baseline C-peptide secretion. The expected inverse relationships between C-peptide and HbA1c or insulin doses varied over time and with age. Combined clinical variables, such as insulin-dose adjusted HbA1c (IDAA1C) and the relationship of IDAA1C to C-peptide, also were influenced by age and time from diagnosis. Models using these clinical measures did not fully predict C-peptide responses. IDAA1C ≤9 underestimated the number of individualswith stimulated C-peptide ≥0.2 nmol/L, especially in children. CONCLUSIONS Current trials of disease-modifying therapy for type 1 diabetes should continue to use C-peptide as a primary end point of β-cell secretory function. Longer duration of follow-up is likely to provide stronger evidence of the effect of diseasemodifying therapy on preservation of β-cell function.

Original languageEnglish (US)
Pages (from-to)1664-1670
Number of pages7
JournalDiabetes Care
Volume39
Issue number10
DOIs
StatePublished - Oct 1 2016

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C-Peptide
Type 1 Diabetes Mellitus
Insulin
Natural History

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Fall in C-peptide during first 4 years from diagnosis of type 1 diabetes : Variable relation to age, HbA1c, and insulin dose. / Hao, Wei; Gitelman, Steven; DiMeglio, Linda; Boulware, David; Greenbaum, Carla J.

In: Diabetes Care, Vol. 39, No. 10, 01.10.2016, p. 1664-1670.

Research output: Contribution to journalArticle

Hao, Wei ; Gitelman, Steven ; DiMeglio, Linda ; Boulware, David ; Greenbaum, Carla J. / Fall in C-peptide during first 4 years from diagnosis of type 1 diabetes : Variable relation to age, HbA1c, and insulin dose. In: Diabetes Care. 2016 ; Vol. 39, No. 10. pp. 1664-1670.
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N2 - OBJECTIVE We aimed to describe the natural history of residual insulin secretion in Type 1 Diabetes TrialNet participants over 4 years from diagnosis and relate this to previously reported alternative clinical measures reflecting β-cell secretory function. RESEARCH DESIGN AND METHODS Data from 407 subjects from 5 TrialNet intervention studies were analyzed. All subjects had baseline stimulated C-peptide values of ≥0.2 nmol/L from mixedmeal tolerance tests (MMTTs). During semiannual visits, C-peptide values from MMTTs, HbA1c, and insulin doses were obtained. RESULTS The percentage of individuals with stimulated C-peptide of ≥0.2 nmol/L or detectable C-peptide of ≥0.017 nmol/L continued to diminish over 4 years; this was markedly influenced by age. At 4 years, only 5% maintained their baseline C-peptide secretion. The expected inverse relationships between C-peptide and HbA1c or insulin doses varied over time and with age. Combined clinical variables, such as insulin-dose adjusted HbA1c (IDAA1C) and the relationship of IDAA1C to C-peptide, also were influenced by age and time from diagnosis. Models using these clinical measures did not fully predict C-peptide responses. IDAA1C ≤9 underestimated the number of individualswith stimulated C-peptide ≥0.2 nmol/L, especially in children. CONCLUSIONS Current trials of disease-modifying therapy for type 1 diabetes should continue to use C-peptide as a primary end point of β-cell secretory function. Longer duration of follow-up is likely to provide stronger evidence of the effect of diseasemodifying therapy on preservation of β-cell function.

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