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

Authors: Yoshiaki Y. Tamura, Naotaka N. Izumiyama-Shimomura, Yoshiyuki Y. Kimbara, Ken-Ichi K. Nakamura, Naoshi N. Ishikawa, Junko J. Aida, Yuko Y. Chiba, Seijiro S. Mori, Tomio T. Arai, Toru T. Aizawa, Atsushi A. Araki, Kaiyo K. Takubo, Hideki H. Ito
Published: 04/15/2014, The Journal of clinical endocrinology and metabolism

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.

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