The long-term effects of fructose as a natural sweetener in the physiologic meals of ambulatory obese patients with type II diabetes remain uncertain. An outpatient 12-week study was therefore conducted to evaluate the metabolic effects of crystalline fructose (60 g) supplementation of the diet of nine patients with type II diabetes (Group A, mean age 57 +/- 2 years, seven women and two men). Their results were compared with age-, sex-, and weight-matched patients with type II diabetes who were similarly studied but without fructose supplementation of their usual meals (Group B). The mean +/- SEM fasting serum glucose (224 +/- 24 versus 204 +/- 14 mg/dl) and glycosylated hemoglobin (11.57 +/- 0.49 versus 10.20 +/- 0.60 percent) values progressively decreased (p less than 0.05, week 12 versus week 0) in Group A. In contrast, both parameters increased in Group B when compared with the week 0 values, but differences were not statistically significant. Levels of fasting serum triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol remained unchanged at week 12 compared with week 0 in Group A. However, the mean apoprotein A1 concentrations increased significantly at weeks 4 and 12 in Group A, whereas only transient changes occurred in apoprotein B100 values. Levels of mean fasting serum triglycerides increased at weeks 4 (15 percent) and 12 (38 percent) in Group B; however, no significant changes occurred in the rest of the lipid, lipoprotein, and apoprotein A1 and B100 levels. Metabolic by-products of fructose such as serum lactic acid and uric acid levels remained essentially unchanged in both groups at the end of the study. In addition, no significant weight changes were observed in either group. The fructose supplementation was well tolerated without significant adverse effects. Thus, this study demonstrates that addition of moderate amounts of fructose as a natural sweetener in the physiologic mixed meal does not appear to have deleterious effects on glycemic control and lipid and lipoprotein metabolism in ambulatory obese patients with type II diabetes and poor metabolic control. Rather, a slight improvement in glycemic control and alterations in the apoprotein compositions in favor of decreased risk for coronary artery disease may occur.