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

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.

Figure 1

Scatterplot of UCPCR against duration. Red dashed reference lines at UCPCR=0.2 nmol/mmol - equivalent to stimulated serum C-peptide of 200 pmol/L, and UCPCR=0.03 - equivalent to serum values of 30 pmol/L, the lower limit of many historical assays, and UCPCR=0.001 nmol/mmol – effective lower limit of detection of this assay). UCPCR values are plotted on a log scale to allow separation of the range of low levels found.

Figure 2

Bar chart of proportion of subjects with UCPCR detectable (>0.001 nmol/mmol) against duration quintile. P<0.0001 for trend of decreasing proportion across duration groups.