OBJECTIVE -Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease. Type 2 diabetes confers an adverse cardiovascular risk profile particularly in women after menopause. The aim of this study was to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance, glycemic control, and cardiovascular risk markers in postmenopausal women with type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a randomized, double blind, cross-over trial of dietary supplementation with phytoestrogens (soy protein 30 g/day, isoflavones 132 mg/day) versus placebo (cellulose 30 g/day) for 12 weeks, separated by a 2-week washout period.RESULTS -Compliance with the dietary supplementation was Ͼ90% for both treatment phases. When compared with the mean percentage change from baseline seen after 12 weeks of placebo, phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin (mean Ϯ SD 8.09 Ϯ 21.9%, P ϭ 0.006), insulin resistance (6.47 Ϯ 27.7%, P ϭ 0.003), HbA 1c (0.64 Ϯ 3.19%, P ϭ 0.048), total cholesterol (4.07 Ϯ 8.13%, P ϭ 0.004), LDL cholesterol (7.09 Ϯ 12.7%, P ϭ 0.001), cholesterol/HDL cholesterol ratio (3.89 Ϯ 11.7%, P ϭ 0.015), and free thyroxine (2.50 Ϯ 8.47%, P ϭ 0.004). No significant change occurred in HDL cholesterol, triglycerides, weight, blood pressure, creatinine, dehydroepiandrosterone sulfate, androstenedione, and the hypothalamic-pituitary-ovarian axis hormones.CONCLUSIONS -These results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance, glycemic control, and serum lipoproteins in postmenopausal women with type 2 diabetes, thereby improving their cardiovascular risk profile. Diabetes Care 25:1709 -1714, 2002C ardiovascular diseases (CVDs), especially coronary heart disease and cerebrovascular disease, are the leading causes of death in women (1). Type 2 diabetes increases the risk of death from CVD by two-to fourfold (2), and women with diabetes are four times more likely to die from CVD than men (3). Postmenopausal estrogen depletion (4) and increased insulin resistance (5) may contribute to the high risk of accelerated CVD in women with type 2 diabetes.Epidemiological data suggest that in Japanese-Americans in Seattle, WA, the prevalence of type 2 diabetes is four times that in Japanese in Tokyo (6,7). Despite very similar degrees of hyperglycemia, the Japanese-Americans with type 2 diabetes showed significantly higher levels of plasma insulin after a 75-g oral glucose tolerance test (OGTT) than Japanese with diabetes (6,8), and BMI correlated with insulin levels only for the JapaneseAmerican men (8). This observation suggested a greater degree of insulin resistance among the Japanese-Americans and that factors other than BMI were responsible for the difference in plasma insulin levels between the two groups (9). Soy is a staple in the diet of the Japanese population, and consumption of soy has ...

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