OBJECTIVE: Although an excess transmission of type 2 diabetes from mothers has been documented, whether this is an independent trait or whether the effect can be detected early through risk factors for type 2 diabetes remains to be elucidated. The objective of this study was to investigate the prevalence of and the possible prospective effect of family history on type 2 diabetes incidence adjusted for multiple diabetes risk factors in a 22.5-year follow-up study of healthy men. RESEARCH DESIGN AND METHODS: A total of 1,947 apparently healthy nondiabetic men with fasting blood glucose (FBG) levels <110 mg/dl at baseline, in whom an intravenous glucose tolerance test (IVGTT) was administered and several conventional risk factors were measured, were followed for 22.5 years. Family history data were obtained at the baseline examination, and morbidity data were obtained from repeated investigations, hospital records, and death certificates. RESULTS: A total of 131 men reported maternal diabetes family history only, 65 men reported paternal diabetes family history only and 10 men reported both maternal and paternal diabetes family history. Among the 1,947 men, 143 cases of type 2 diabetes developed during 22.5 years of observation. Maternal family history and combined maternal and paternal family history predisposed to future type 2 diabetes both in univariate Cox analysis and in multivariate Cox regression analysis after adjusting for glucose disappearance rate (Rd) during an IVGTT, FBG level, BMI, physical fitness, triglyceride level, and age. Maternal family history showed a relative risk (RR) of 2.51 (95% CI 1.55-4.07), combined maternal and paternal family history showed an RR of 3.96 (1.22-12.9), and paternal family history showed an RR of 1.41 (0.657-3.05) in multivariate analysis. CONCLUSIONS: Maternal family history appears to be an important risk factor for type 2 diabetes independent of prediabetic Rd, FBG, BMI, and physical fitness levels.

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