Dietary recommendations for diabetic patients now generally include the reduction of total and saturated fat and an increase in complex carbohydrates. We conducted two series of studies on individuals with obesity and/or non-insulin-dependent diabetes mellitus (NIDDM) to assess the effects of this dietary recommendation on both lipoproteins and their metabolism as well as on insulin secretion and action and energy expenditure. Both series compared a diet high in saturated fat with a diet high in complex carbohydrates and fiber. Calories and proportion of protein were constant. In the first set of studies, we sought to examine the effect of replacement of saturated fat with complex carbohydrate in a regimen with conventional foods that would closely approximate foods expected to be used and recommended to diabetic patients. In the second regimen, we examined a more extreme difference between carbohydrate content and fat content using a dietary change that would approximate the contrasts between traditional diets of Native Americans or other cultures and a modern westernized diet. The effects on lipoproteins included consistent decreases in total and low-density lipoprotein (LDL) cholesterol (av 10%), minimum to no change in high-density lipoprotein cholesterol, and insignificant changes in total or very-low-density lipoprotein (VLDL) triglycerides or 24-h triglyceride profiles. Changes in total and LDL cholesterol required 3-4 wk to reach equilibrium. Metabolic studies used to elucidate the reasons for the decrease in LDL cholesterol confirmed no stimulation of VLDL triglyceride or apolipoprotein B (apoB) production on the high-carbohydrate diet. The decrease in LDL appeared to be due to decreases in mechanisms that convert VLDL to LDL and increased activity of LDL apoB clearance. There were no changes in fasting and 2- or 24-h glucose profiles or in fasting and 2-h insulin concentrations in individuals consuming a diet of 30% fat and 55% carbohydrate. However, in the study with traditional foods, where dietary carbohydrate was 70% and fat only 15%, there was an improvement in glucose tolerance. It was accompanied by an improvement in glucose-mediated glucose disposal and insulin secretion. Finally, with a whole-body calorimeter, we found no difference between the high-fat and high-carbohydrate diets in terms of 24-h energy expenditure. In individuals having a wide range of obesity and glucose tolerance, substitution of complex carbohydrates for saturated fat has beneficial effects of lowering LDL cholesterol and possibly improving glucose tolerance and insulin secretion but without having any adverse effects on lipoprotein metabolism or energy expenditure.