It is commonly believed that high-carbohydrate (CHO) diets improve peripheral insulin sensitivity; however, this concept is based on anecdotal evidence. Furthermore, it has been demonstrated that in non-insulin-dependent diabetic patients treated with insulin, a high-monounsaturated-fat (MUFA) diet is more effective than a high-complex-CHO diet in reducing blood glucose levels. The aim of our study was to compare the effect of a high-MUFA diet and a high-CHO diet on peripheral insulin sensitivity and metabolic control in non-insulin-dependent diabetic patients. Ten non-insulin-dependent diabetic patients aged 52 +/- 8 years with a body mass index (BMI) of 26.7 +/- 3.5 kg/m2 who were being treated with diet alone (n = 5) or with diet plus glibenclamide (n = 5) were randomly assigned to a 15-day period of either a high-MUFA/low-CHO diet (CHO, 40%; fat, 40%; protein, 20%; fiber, 24g) or a low-MUFA/high-CHO diet (CHO, 60%; fat, 20%; protein, 20%; fiber, 24g) and were then crossed-over to the other diet. Diets were similar in their content of monosaccharides, disaccharides, and saturated fats, and were administered to the patients in a metabolic ward. The dosage of hypoglycemic drugs was maintained at a constant level throughout the study. With the high-MUFA/low-CHO diet, a decrease in both postprandial glucose (8.76 +/- 2.12 v 10.08 +/- 2.76 mmol/L; P < .05) and plasma insulin (195.0 +/- 86.4 v 224.4 +/- 75.6 pmol/L; P < .02) levels was observed. Furthermore, fasting plasma triglyceride levels were reduced after the high-MUFA fat/low-CHO diet (1.16 +/- 0.59 v 1.37 +/- 0.59 mmol/L; P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)