Insulin Sensitivity and Insulin Secretion Determined by Homeostasis Model Assessment and Risk of Diabetes in a Multiethnic Cohort of Women The Women's Health Initiative Observational Study Yiqing Song , MD, SCD 1 , JoAnn E. Manson , MD, DRPH 1 2 , Lesley Tinker , PHD, RD 3 , Barbara V. Howard , PHD 4 , Lewis H. Kuller , MD, DRPH 5 , Lauren Nathan , MD 6 , Nader Rifai , PHD 7 and Simin Liu , MD, SCD 1 2 8 9 1 Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 2 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 3 Public Health Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 4 MedStar Research Institute, Washington, D.C. 5 Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania 6 Department of Obstetrics and Gynecology, University of California, Los Angeles, Los Angeles, California 7 Children's Hospital, Boston, Massachusetts 8 Department of Epidemiology, University of California, Los Angeles, School of Public Health, Los Angeles, California 9 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California Address correspondence and reprint requests to Prof. Simin Liu, Department of Epidemiology, UCLA School of Public Health, Box 951772, 650 Charles E. Young Dr. South, Los Angeles, CA 90095. E-mail: siminliu{at}ucla.edu Abstract OBJECTIVE — The homeostasis model assessment (HOMA), based on plasma levels of fasting glucose and insulin, has been widely validated and applied for quantifying insulin resistance and β-cell function. However, prospective data regarding its relation to diabetes risk in ethnically diverse populations are limited. RESEARCH DESIGN AND METHODS — Among 82,069 women who were aged 50–79 years, free of cardiovascular disease or diabetes, and participating in the Women's Health Initiative Observational Study, we conducted a nested case-control study to prospectively examine the relations of HOMA of insulin resistance (HOMA-IR) and β-cell function (HOMA-B) with diabetes risk. During a median follow-up period of 5.9 years, 1,584 diabetic patients were matched with 2,198 control subjects by age, ethnicity, clinical center, time of blood draw, and follow-up time. RESULTS — Baseline levels of fasting glucose, insulin, and HOMA-IR were each significantly higher among case compared with control subjects, while HOMA-B was lower (all P values <0.0001). After adjustment for matching factors and diabetes risk factors, all four markers were significantly associated with diabetes risk; the estimated relative risks per SD increment were 3.54 (95% CI 3.02–4.13) for fasting glucose, 2.25 (1.99–2.54) for fasting insulin, 3.40 (2.95–3.92) for HOMA-IR, and 0.57(0.51–0.63) for HOMA-B. While no statistically significant multiplicative interactions were observed between these markers and ethnicity, the associations of both HOMA-IR and HOMA-B with diabetes risk remained significant and robust in each ethnic group, including whites, blacks, Hispanics, and Asians/Pacific Islanders. When evaluated jointly, the relations of HOMA-IR and HOMA-B with diabetes risk appeared to be independent and additive. HOMA-IR was more strongly associated with an increased risk than were other markers after we excluded those with fasting glucose ≥126 mg/dl at baseline. CONCLUSIONS — High HOMA-IR and low HOMA-B were independently and consistently associated with an increased diabetes risk in a multiethnic cohort of U.S. postmenopausal women. These data suggest the value of HOMA indexes for diabetes risk in epidemiologic studies. HOMA, homeostasis model assessment HOMA-B, HOMA of β-cell function HOMA-IR, HOMA of insulin resistance IGT, impaired glucose tolerance NGT, normal glucose tolerance WHI-OS, Women's Health Initiative Observational Study Footnotes Published ahead of print at http://care.diabetesjournals.org on 27 April 2007. DOI: 10.2337/dc07-0358. Additional information for this article, as well as a list of WHI investigators, can be viewed in an online appendix at http://dx.doi.org/10.2337/dc07-0358 . A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact. Accepted April 14, 2007. Received February 20, 2007. DIABETES CARE