Most people with long-duration type 1 diabetes in a large population-based study are insulin microsecretors

Richard A. Oram, Timothy J. McDonald, Beverley M. Shields, Michelle M. Hudson, Maggie H. Shepherd, Suzanne Hammersley, Ewan R. Pearson, Andrew T. Hattersley, on behalf of the UNITED Team

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    Abstract

    OBJECTIVE: Small studies using ultrasensitive C-peptide assays suggest endogenous insulin secretion is frequently detectable in patients with long-standing type 1 diabetes (T1D), but these studies do not use representative samples. We aimed to use the stimulated urine C-peptide-to-creatinine ratio (UCPCR) to assess C-peptide levels in a large cross-sectional, population-based study of patients with T1D. RESEARCH DESIGN AND METHODS: We recruited 924 patients from primary and secondary care in two U.K. centers who had a clinical diagnosis of T1D, were under 30 years of age when they received a diagnosis, and had a diabetes duration of >5 years. The median age at diagnosis was 11 years (interquartile range 6-17 years), and the duration of diabetes was 19 years (11-27 years). All provided a home postmeal UCPCR, which was measured using a Roche electrochemiluminescence assay. RESULTS: Eighty percent of patients (740 of 924 patients) had detectable endogenous C-peptide levels (UCPCR >0.001 nmol/mmol). Most patients (52%, 483 of 924 patients) had historically very low undetectable levels (UCPCR 0.0013-0.03 nmol/mmol); 8% of patients (70 of 924 patients) had a UCPCR ≥0.2 nmol/mmol, equivalent to serum levels associated with reduced complications and hypoglycemia. Absolute UCPCR levels fell with duration of disease. Age at diagnosis and duration of diseasewere independent predictors of C-peptide level in multivariate modeling. CONCLUSIONS: This population-based study shows that the majority of long-duration T1D patients have detectable urine C-peptide levels. While the majority of patients are insulin microsecretors, some maintain clinically relevant endogenous insulin secretion for many years after the diagnosis of diabetes. Understanding this may lead to a better understanding of pathogenesis in T1D and open new possibilities for treatment.

    Original languageEnglish
    Pages (from-to)323-328
    Number of pages6
    JournalDiabetes Care
    Volume38
    Issue number2
    DOIs
    Publication statusPublished - Feb 2015

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    Oram, R. A., McDonald, T. J., Shields, B. M., Hudson, M. M., Shepherd, M. H., Hammersley, S., Pearson, E. R., Hattersley, A. T., & on behalf of the UNITED Team (2015). Most people with long-duration type 1 diabetes in a large population-based study are insulin microsecretors. Diabetes Care, 38(2), 323-328. https://doi.org/10.2337/dc14-0871