β-cell telomere attrition in diabetes: inverse correlation between HbA1c and telomere length

J Clin Endocrinol Metab. 2014 Aug;99(8):2771-7. doi: 10.1210/jc.2014-1222. Epub 2014 Apr 15.

Abstract

Context: Although accelerated β-cell telomere shortening may be associated with diabetes that shows a dramatically increased incidence with aging, β-cell telomere length in diabetes has never been explored.

Objective: The objective of the present study was to examine telomere length in the β-cells of patients with diabetes.

Design and patients: We determined telomere length in β- and α-cells of pancreases obtained at autopsy from 47 patients with type 2 diabetes and 51 controls, all older than 60 years.

Main outcome measure: The normalized telomere to centromere ratio (NTCR), an index of telomere length, was determined for β- (NTCRβ) and α- (NTCRα) cells by quantitative fluorescence in situ hybridization.

Results: The NTCRβ was reduced by 27% ± 25% and NTCRα by 15% ± 27% in the patients with diabetes relative to the controls (P < .01 for both). Importantly, the degree of shortening was significantly (P < .01) greater in β-cells than in α-cells. The histogram of NTCR distribution was significantly skewed to the left in the patients with diabetes relative to the controls for both β- and α-cells, indicating preferential depletion of longer-telomere islet cells. Glycated hemoglobin was negatively correlated with β-cell telomere length, and the telomeres were significantly shorter in patients who had used hypoglycemic agents than in those who had not.

Conclusion: The telomeres of β-cells are shortened in patients with type 2 diabetes. There may be a vicious cycle involving β-cell telomere attrition and sustained hyperglycemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / blood
  • Aging / genetics
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Male
  • Telomere / metabolism
  • Telomere Shortening*

Substances

  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human