BACKGROUND/OBJECTIVES: There is controversy over dietary protein's effects on cardiovascular disease risk factors in diabetic subjects. It is unclear whether observed effects are due to increased protein or reduced carbohydrate content of the consumed diets. The aim of this study was to compare the effects of two diets differing in protein to fat ratios on cardiovascular disease risk factors. SUBJECTS/METHODS: A total of 17 obese (body mass index (BMI) ranging from 31 to 45 kg/m(2)) volunteers with type 2 diabetes (DM2), aged 46+/-3 years, consumed two diets, each for 4 weeks, with 3 weeks of washout period in a random, blind, crossover design. The diets were: (1) a high-protein low-fat diet (HP-LF, with 30% protein, 50% carbohydrates and 20% fat) and (2) a low-protein high-fat diet (LP-HF, with 15% protein, 50% carbohydrates and 35% fat). Their effects on fasting glycemic control, lipid levels and blood pressure, and on postprandial glucose and insulin responses after a standard test meal at the beginning and end of each dietary intervention were analyzed. RESULTS: Both diets were equally effective in promoting weight loss and fat loss and in improving fasting glycemic control, total cholesterol and low-density lipoprotein (LDL) cholesterol, but the HP-LF diet decreased to a greater extent triglyceride (TG) levels (P=0.04) when compared with the LP-HF diet. HP-LF diet improved significantly both systolic and diastolic blood pressure when compared with the LP-HF diet (P<0.001 and P<0.001, respectively). No differences were observed in postprandial glucose and insulin responses. CONCLUSIONS: A protein to fat ratio of 1.5 in diets significantly improves blood pressure and TG concentrations in obese individuals with DM2.