β-Cell Telomere Attrition in Diabetes: Inverse Correlation Between HbA1c and Telomere Length

CONTEXT: Although accelerated β-cell telomere(definition) 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.