Insulin Sensitivity and Insulin Secretion Determined by Homeostasis Model Assessment and Risk of Diabetes in a Multiethnic Cohort of Women

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.

[1]  S. Haffner,et al.  The Homeostasis Model in the San Antonio Heart Study , 1997, Diabetes Care.

[2]  Y. Ueki,et al.  Glucose Tolerance, Insulin Secretion, and Insulin Sensitivity in Nonobese and Obese Japanese Subjects , 1997, Diabetes Care.

[3]  M. Davidson.  Status of research funded by the American Diabetes Association: year 3. , 2002, Diabetes care.

[4]  R. Bergman,et al.  Utility of a surrogate measure of insulin resistance in American Indians: the Strong Heart Study. , 2002, Ethnicity & disease.

[5]  P. Chou,et al.  Relative role of insulin resistance and beta-cell dysfunction in the progression to type 2 diabetes--The Kinmen Study. , 2003, Diabetes research and clinical practice.

[6]  D. Schuster,et al.  Impaired insulin sensitivity, insulin secretion, and glucose effectiveness predict future development of impaired glucose tolerance and type 2 diabetes in pre-diabetic African Americans: implications for primary diabetes prevention. , 2004, Diabetes care.

[7]  M. Stumvoll,et al.  Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. , 2000, Diabetes care.

[8]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[9]  S. Kahn,et al.  Visceral adiposity and the risk of impaired glucose tolerance: a prospective study among Japanese Americans. , 2003, Diabetes care.

[10]  J. Manson,et al.  Circulating Levels of Endothelial Adhesion Molecules and Risk of Diabetes in an Ethnically Diverse Cohort of Women , 2007, Diabetes.

[11]  A. Avignon,et al.  Assessment of insulin sensitivity from plasma insulin and glucose in the fasting or post oral glucose-load state , 1999, International Journal of Obesity.

[12]  J. Manson,et al.  A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women. , 2007, Archives of internal medicine.

[13]  T. Shoji,et al.  Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas. , 1999, Diabetes care.

[14]  E. Gabazza,et al.  Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes. , 2001, Diabetes care.

[15]  K. Tokuyama,et al.  Assessment of insulin sensitivity and insulin secretion from the oral glucose tolerance test in nonobese Japanese type 2 diabetic patients: comparison with minimal-model approach. , 2000, Diabetes care.

[16]  Scott Davis,et al.  Implementation of the Women's Health Initiative study design. , 2003, Annals of epidemiology.

[17]  S. Haffner,et al.  A Prospective Analysis of the HOMA Model: The Mexico City Diabetes Study , 1996, Diabetes Care.

[18]  Ralph B D'Agostino,et al.  Prediction of type 2 diabetes using simple measures of insulin resistance: combined results from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study. , 2003, Diabetes.

[19]  S. Park,et al.  Limitation of the validity of the homeostasis model assessment as an index of insulin resistance in Korea. , 2005, Metabolism: clinical and experimental.

[20]  J. Levy,et al.  Use and abuse of HOMA modeling. , 2004, Diabetes care.

[21]  Insulin sensitivity indexes from a single sample in nonobese Japanese type 2 diabetic patients: comparison with minimal model analysis. , 2002, Diabetes care.

[22]  Michele Muggeo,et al.  Population-based incidence rates and risk factors for type 2 diabetes in white individuals: the Bruneck study. , 2004, Diabetes.

[23]  G. Fiestras-Janeiro,et al.  Comparison of several insulin sensitivity indices derived from basal plasma insulin and glucose levels with minimal model indices. , 2003, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[24]  E. Bonora,et al.  Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. , 2000, Diabetes care.