OBJECTIVE--To study effects of high carbohydrate intake on hyperglycemia, islet functions, and plasma lipoproteins in patients with NIDDM. RESEARCH DESIGN AND METHODS--An attempt was made to induce hyperglycemia in 10 men with NIDDM by feeding them an isocaloric high-carbohydrate diet (65% of energy as simple carbohydrates [31% as glucose] and 20% as fat) for 28 days in a metabolic ward. Response to the high-carbohydrate diet was compared with that of feeding a diet rich in monounsaturated fat (45% of energy as fat [31% as monounsaturated fat] and 38% as carbohydrates) for 28 days in a cross-over manner. Islet functions were assessed by evaluating plasma glucose, insulin, C-peptide and glucagon responses to standard meal tolerance tests on days 0, 14, 21, and 28 of each dietary period. Fasting plasma lipoproteins were determined during the last week of each dietary period. RESULTS--The high-carbohydrate diet caused significant but modest accentuation of hyperglycemia, particularly in patients with moderately severe diabetes mellitus, whereas no change was observed with the high-monounsaturated fatty-acid diet. Accentuation of hyperglycemia was accompanied by an increase in plasma glucagon levels, but no significant change in insulin and C-peptide responses. In 1 patient, feeding the high-carbohydrate diet for 68 days produced marked hyperglycemia and caused definite suppression of insulin and C-peptide responses along with an increase in glucagon levels. Compared with the high-monounsaturated fat diet, the high-carbohydrate diet also raised plasma triglyceride and VLDL cholesterol concentrations. CONCLUSIONS--High-carbohydrate diets may cause accentuation of hyperglycemia and a rise in plasma glucagon levels in NIDDM patients. High-carbohydrate diets also adversely affect lipoproteins and therefore may not be desirable in all NIDDM patients.