OBJECTIVE:To investigate whether glycemic and lipid control in patients with non-insulin-dependent diabetes (NIDDM) can be significantly improved using a low-fat, vegetarian (vegan) diet in the absence of recommendations regarding exercise or other lifestyle changes. METHODS:Eleven subjects with NIDDM recruited from the Georgetown University Medical Center or the local community were randomly assigned to a low-fat vegan diet (seven subjects) or a conventional low-fat diet (four subjects). Two additional subjects assigned to the control group failed to complete the study. The diets were not designed to be isocaloric. Fasting serum glucose, body weight, medication use, and blood pressure were assessed at baseline and biweekly thereafter for 12 weeks. Serum lipids, glycosylated hemoglobin, urinary albumin, and dietary macronutrients were assessed at baseline and 12 weeks. RESULTS:Although the sample was intentionally small in accordance with the pilot study design, the 28% mean reduction in fasting serum glucose of the experimental group, from 10.7 to 7.75 mmol/L (195 to 141 mg/dl), was significantly greater than the 12% decrease, from 9.86 to 8.64 mmol/L (179 to 157 mg/dl), for the control group (P < 0.05). The mean weight loss was 7.2 kg in the experimental group, compared to 3. 8 kg for the control group (P < 0.005). Of six experimental group subjects on oral hypoglycemic agents, medication use was discontinued in one and reduced in three. Insulin was reduced in both experimental group patients on insulin. No patient in the control group reduced medication use. Differences between the diet groups in the reductions of serum cholesterol and 24-h microalbuminuria did not reach statistical significance; however, high-density lipoprotein concentration fell more sharply (0.20 mmol/L) in the experimental group than in the control group (0.02 mmol/L) (P < 0.05). CONCLUSION:The use of a low-fat, vegetarian diet in patients with NIDDM was associated with significant reductions in fasting serum glucose concentration and body weight in the absence of recommendations for exercise. A larger study is needed for confirmation.