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

Diabetes Metab Res Rev. 2014 Feb;30(2):154-62. doi: 10.1002/dmrr.2478.

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 β 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.

Trial registration: ClinicalTrials.gov NCT00129259 NCT00378508.

Keywords: insulin secretion rates; long duration; type 1 diabetes.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • C-Peptide / blood
  • Child
  • Cohort Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Disease Progression*
  • Down-Regulation* / drug effects
  • Female
  • Glucagon / metabolism
  • Glucagon-Secreting Cells / drug effects
  • Glucagon-Secreting Cells / metabolism
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / metabolism*
  • Insulin / therapeutic use
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Male
  • Postprandial Period
  • Young Adult

Substances

  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • hemoglobin A1c protein, human
  • Glucagon

Associated data

  • ClinicalTrials.gov/NCT00129259
  • ClinicalTrials.gov/NCT00378508