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C-peptide in Age at Diagnosis and Duration of T1DM Population

Certain individuals may show detectable levels of C-peptide depending on time of diagnosis…

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Measurement of C-peptide has been a frequently used method when quantifying endogenous insulin secretion and observing beta-cell functioning. Fasting and random measures of C-peptide can be used. Mixed-meal tolerance test (MMTT) has also been used to measure stimulated C-peptide and has been validated and is used as the primary end point measure in clinical trials when looking to assess insulin secretion in type 1 diabetes.

A team of researchers from ten institutions across the U.S. measured the frequency of residual insulin secretion in individuals at different ages of diagnosis.

The study was conducted at 28 sites participating in the T1D Exchange Clinic Network after institutional review board approval at each site and informed consent was obtained. The frequency of residual insulin secretion was determined by measurement of non-fasting serum C-peptide concentration in 919 individuals with type 1 diabetes. Participants were placed in pre-specified groups based on age at diagnosis and duration of disease (from 3 to 81 years duration). The participants with detectable non-fasting C-peptide (≥0.017 nmol/L) and non-fasting C-peptide (≥0.2 nmol/L) were classified in subgroups according to diagnosis age and duration of diabetes. Logistic regression models were performed to assess whether diagnosis age and diabetes duration (as continuous variables) were independently associated with the prevalence of detectable C-peptide. For validation purposes, this analysis was replicated in a subgroup of the participants who were diagnosed at <10 years of age or had positive pancreatic autoantibodies at any time (GAD, islet antigen 2, islet cell antibody, or zinc transporter-8).

The overall frequency of detectable non-fasting C-peptide was 29% (95% CI 26 to 32%), and the frequency of non-fasting C-peptide was 10% (95% CI 8 to 12%). This was shown to decrease with time from diagnosis regardless of age at diagnosis. The number of subjects with detectable non-fasting C-peptide decreased with a longer duration of type 1 diabetes but was consistently higher when onset had occurred at >18 years of age compared with ≤18 years of age. Of those with undetectable non-fasting C-peptide, 19% were observed to be C-peptide positive when stimulation testing was used.

In conclusion, data from this study suggest that remaining secretion is present in about one out of three individuals who are 3 or more years from the diagnosis of type 1 diabetes. The rate of occurrence of remaining C-peptide was shown to decrease with time from diagnosis regardless of age at diagnosis. The study also shows that during all durations of disease and diagnosis when >18 years of age was associated with greater frequency and higher values of C-peptide.

Practice Pearls:

  • The participants in this study were predominantly Caucasian and non-Hispanic.
  • Data suggest important differences in the biological process of type 1 diabetes between those diagnosed as children or as adults that may be useful for further research.
  • Centers for Medicare and Medicaid Services will provide payment for the use of subcutaneous insulin infusion (insulin pumps) for patients with type 1 diabetes; however, one criteria for coverage is low or absent C-peptide.

Asa K. Davis. "Prevalence of Detectable C-Peptide According to Age at Diagnosis and Duration of Type 1 Diabetes". Diabetes Care. March 2015;38:476–481.