Characterization of residual ß cell function in long-standing type 1 diabetes.

ABSTRACT

BACKGROUND: Some patients with long-standing type 1 diabetes (T1D) maintain detectable levels of C-peptide. The quantitative and qualitative aspects of insulin secretion in these subjects have not been assessed, but may shed light on the basis for maintained ß cell function. Our objective was to characterize insulin secretion in subjects with varying duration of T1D. METHODS: Data from mixed-meal tolerance tests were collected in this cross-sectional study. We screened 58 subjects with T1D <1 year and 34 subjects with T1D >2 years, 20 of whom had previously participated in trials of anti-CD3 monoclonal antibody. Data from 38 historical non-diabetic controls were utilized. Insulin secretory rates were calculated from C-peptide levels from mixed-meal tolerance tests. Patterns and rates of insulin secretion were characterized along with relationships between insulin secretion and clinical parameters. RESULTS: C-peptide was detected in 68% of subjects with T1D duration >2 years. Insulin secretion was negatively correlated with HgbA(1c) and insulin use. A decline in total insulin secretion was seen with increasing disease duration (p < 0.0001). More subjects with long duration of T1D had a delayed time to peak secretion compared with those with new onset T1D or non-diabetic subjects. Insulin and glucagon secretory responses appeared unrelated. CONCLUSIONS: Meal-stimulated insulin secretory responses are seen in those with long-standing T1D and detectable C-peptide. Delayed insulin secretory responses are more common in individuals with longer disease duration. Residual insulin secretory responses are associated with improved clinical parameters.