A Prospective Study of Leukocyte Telomere Length and Risk of Type 2 Diabetes in Postmenopausal Women
- Nai-chieh Y. You1,2,
- Brian H. Chen1,2,
- Yiqing Song3,
- XuYang Lu1,2,4,
- Yilin Chen1,2,
- JoAnn E. Manson3,
- Mo Kang2,5,
- Barbara V. Howard6,7,
- Karen L. Margolis8,
- J. David Curb9,
- Lawrence S. Phillips10,11,
- Marcia L. Stefanick12,
- Lesley F. Tinker13 and
- Simin Liu1,2,14⇓
- 1Program on Genomics and Nutrition, Department of Epidemiology, Fielding School of Public Health, and Departments of Medicine and Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, California
- 2Center for Metabolic Disease Prevention, UCLA, Los Angeles, California
- 3Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
- 4Department of Biostatistics, UCLA, Los Angeles, California
- 5Division of Associated Clinical Sciences, School of Dentistry, UCLA, Los Angeles, California
- 6MedStar Research Institute, Hyattsville, Maryland
- 7Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC
- 8Health Partners Research Foundation, Minneapolis, Minnesota
- 9John A. Burns School of Medicine, University of Hawaii, and Pacific Health Research Institute, Honolulu, Hawaii
- 10Atlanta VA Medical Center, Decatur, Georgia
- 11Emory University School of Medicine, Atlanta, Georgia
- 12Stanford Prevention Research Center, School of Medicine, Stanford University, Stanford, California
- 13Fred Hutchinson Cancer Research Center, Seattle, Washington
- 14Johnson Comprehensive Cancer Center, UCLA, Los Angeles, California
- Corresponding author: Simin Liu, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-0241/-/DC1.
- Received February 27, 2012.
- Accepted May 4, 2012.
- © 2012 by the American Diabetes Association.
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