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Diabetes Care. 2015 Feb;38(2):323-8. doi: 10.2337/dc14-0871. Epub 2014 Dec 17.

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

Author information

1
National Institute for Health Research, Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K.
2
National Institute for Health Research, Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K. Department of Blood Sciences, Royal Devon and Exeter NHS Foundation Trust, Exeter, U.K.
3
Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, U.K.
4
National Institute for Health Research, Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K. a.t.hattersley@exeter.ac.uk.

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 disease were 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.

PMID:
25519449
PMCID:
PMC5646646
DOI:
10.2337/dc14-0871
[Indexed for MEDLINE]
Free PMC Article

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