title: β-cell telomere attrition in diabetes: inverse correlation between HbA1c and telomere length.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Diabetes, Metabolism, and Endocrinology (Y.T., Y.K., Y.C., S.M., A.A., H.I.) and Pathology (T.Ar.), Tokyo Metropolitan Geriatric Hospital, and Research Team for Geriatric Pathology and Department of Pathology (N.I.-S., K.N., N.I., J.A., K.T.), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo 173-0015, Japan; and Diabetes Center (T.Ai.), Aizawa Hospital, Matsumoto, Nagano 390-8510, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Naotaka
authors.initials: N
authors.lastname: Izumiyama-Shimomura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kimbara
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Naoshi
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Junko
authors.initials: J
authors.lastname: Aida
authors.forename: Yuko
authors.initials: Y
authors.lastname: Chiba
authors.forename: Seijiro
authors.initials: S
authors.lastname: Mori
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.forename: Toru
authors.initials: T
authors.lastname: Aizawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Araki
authors.forename: Kaiyo
authors.initials: K
authors.lastname: Takubo
authors.forename: Hideki
authors.initials: H
authors.lastname: Ito
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016615:Telomere / Q000378:metabolism; D059506:Telomere Shortening
chemical_list: D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human