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Little is known about the role of lifestyle factors in non-insulin-dependent diabetes mellitus (NIDDM) incidence among Mexican-Americans. Therefore, we examined whether baseline lifestyle factors predictive of 8-year NIDDM incidence differ in Mexican-American men and women.We studied 353 Mexican-American men and 491 Mexican-American women free of diabetes at baseline who participated in the San Antonio Heart Study follow-up. Lifestyle factors examined were body mass index (BMI), energy intake (total calories/kg), grams of alcohol consumed per week, efforts to control weight by dieting and exercise, leisure physical activity, sugar avoidance, saturated fat/cholesterol avoidance, and 24-h dietary recall assessment of total calories and percentage of calories from total carbohydrate, sucrose, and starch and from total, saturated, monounsaturated, and polyunsaturated fat. Incidence of NIDDM was regressed on lifestyle factors separately for men and women using a backward elimination procedure.Lifestyle factors significantly associated with NIDDM incidence differed for the two sexes. In men, leisure physical activity was inversely associated and alcohol consumption, weight control by dieting, and BMI were positively associated with NIDDM. In women, BMI was positively associated with NIDDM and was the strongest lifestyle predictor. Sugar avoidance and leisure physical activity were also associated with increased NIDDM risk, while weight control by dieting was associated with decreased NIDDM risk. Saturated fat/cholesterol avoidance, grams of alcohol consumed per week, and energy intake were also negatively and indirectly associated with NIDDM in women by means of their direct effects on BMI.It may be important to tailor interventions designed to prevent NIDDM in Mexican-Americans to address sex differences in lifestyle precursors of this disease.