A Prospective Study of Leukocyte Telomere Length and Risk of Type 2 Diabetes in Postmenopausal Women

• Type of Material: Article
• Authors: Nai-chieh Y. You, University of California Los Angeles; Brian H. Chen, University of California Los Angeles; Yiqing Song, Brigham & Women's Hospital; XuYang Lu, University of California Los Angeles; Yilin Chen, University of California Los Angeles; JoAnn E. Manson, Brigham & Women's Hospital; Mo Kang, University of California Los Angeles; Barbara V. Howard, MedStar Research Institute; Karen L. Margolis, Health Partners Research Foundation; J. David Curb, University of Hawaii; Lawrence Phillips, Emory University; Marcia L. Stefanick, Stanford University; Lesley F. Tinker, Fred Hutchinson Cancer Research Center; Simin Liu, University of California Los Angeles
• Language: English
• Date: 2012-11-01
• Publisher: AMER DIABETES ASSOC
• Publication Version: Final Published Version
• Copyright Statement: © 2012 by the American Diabetes Association.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.2337/db12-0241
• Title of Journal or Parent Work: DIABETES
• Volume: 61
• Issue: 11
• Start Page: 2998
• End Page: 3004
• Grant/Funding Information: The Women’s Health Initiative program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services, through contracts N01-WH-22110, -24152, -32100-2, -32105-6, -32108-9, -32111-13, -32115, -32118, -32119, -32122, -42107-26, -42129-32, and -44221. This ancillary study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (R21-DK-084452).
• Keywords: Endocrinology & Metabolism; OXIDATIVE STRESS; MENDELIAN RANDOMIZATION; ASSOCIATION; Life Sciences & Biomedicine; PROTEIN; Science & Technology; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; POT1; HUMAN FIBROBLASTS; MULTIETHNIC COHORT; HEALTH
• Research Categories: Biology, Biostatistics; Health Sciences, Public Health; Biology, Genetics; Health Sciences, Nutrition

Abstract

Telomere length (TL) has been implicated in the pathogenesis of age-related disorders. However, there are no prospective studies directly investigating the role of TL and relevant genes in diabetes development. In the multiethnic Women's Health Initiative, we identified 1,675 incident diabetes case participants in 6 years of follow-up and 2,382 control participants matched by age, ethnicity, clinical center, time of blood draw, and follow-up duration. Leukocyte TL at baseline was measured using quantitative PCR, and Mendelian randomization analysis was conducted to test whether TL is causally associated with diabetes risk. After adjustment for matching and known diabetes risk factors, odds ratios per 1-kilobase increment were 1.00 (95% CI 0.90-1.11) in whites, 0.95 (0.85-1.06) in blacks, 0.96 (0.79-1.17) in Hispanics, and 0.88 (0.70-1.10) in Asians. Of the 80 single nucleotide polymorphisms (SNPs) in nine genes involved in telomere regulation, 14 SNPs were predictive of TL, but none were significantly associated with diabetes risk. Using ethnicity-specific SNPs as randomization instruments, we observed no statistically significant association between TL and diabetes risk (P = 0.52). Although leukocyte TL was weakly associated with diabetes risk, this association was not independent of known risk factors. These prospective findings indicate limited clinical utility of TL in diabetes risk stratification among postmenopausal women.