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Few multiple lifestyle behavior change programs have been designed to reduce the risk of coronary heart disease in postmenopausal women with type 2 diabetes. This study tested the effectiveness of the Mediterranean Lifestyle Program (MLP), a comprehensive lifestyle self-management program (Mediterranean low-saturated fat diet, stress management training, exercise, group support, and smoking cessation), in reducing cardiovascular risk factors in postmenopausal women with type 2 diabetes.Postmenopausal women with type 2 diabetes (n = 279) were randomized to either usual care (control) or treatment (MLP) conditions. MLP participants took part in an initial 3-day retreat, followed by 6 months of weekly meetings, to learn and practice program components. Biological end points were changes in HbA1c, lipid profiles, BMI, blood pressure, plasma fatty acids, and flexibility. Impact on quality of life was assessed.Multivariate ANCOVAs revealed significantly greater improvements in the MLP condition compared with the usual care group on HbA1c, BMI, plasma fatty acids, and quality of life at the 6-month follow-up. Patterns favoring intervention were seen in lipids, blood pressure, and flexibility but did not reach statistical significance.These results demonstrate that postmenopausal women with type 2 diabetes can make comprehensive lifestyle changes that may lead to clinically significant improvements in glycemic control, some coronary heart disease risk factors, and quality of life.