Background: Conversion of glucose into Lipid (de novo lipogenesis: BNL) is a possible fate of carbohydrate administered during nutritional support. It cannot be detected by conventional methods such as indirect calorimetry if it does not exceed lipid oxidation. Objective: The objective was to evaluate the effects of carbohydrate administered as part of continuous enteral nutrition in critically ill patients. Design: This was a prospective. open study including 25 patients nonconsecutively admitted to a medicosurgical intensive care unit. Glucose metabolism and hepatic DNL, were measured in the fasting state or after 3 d of continuous isoenergetic enteral feeding providing 28%, 53%, or 75% carbohydrate. Results: DNL increased with increasing carbohydrate intake ((x) over bar +/- SEM: 7.5 +/- 1.28 with 28% carbohydrate, 9.2 +/- 1.5% with 53% carbohydrate, and 19.4 +/- 3.8% with 75% carbohydrate) and was nearly zero in a group of patients who had fasted for an average of 28 h (1.0 +/- 0.2%). In multiple regression analysis, DNL was correlated with carbohydrate intake, but not with body weight or plasma insulin concentrations. Endogenous glucose production. assessed with a dual-isotope technique, :vas not significantly different between the 3 groups of patients (13.7-15.3 mu mol.kg(-1).min(-1)), indicating impaired suppression by carbohydrate feeding. Gluconeogenesis was measured with [C-13]bicarbonate, and increased as the carbohydrate intake increased (from 2.1 +/- 0.5 mu mol.kg(-10).min(-1) with 28% carbohydrate intake to 3.7 +/- 0.3 mu mol.kg(-1).min(-1) with 75% carbohydrate intake, P < 0.05). Conclusion: Carbohydrate feeding fails to suppress endogenous glucose production and gluconeogenesis, but stimulates DNL in critically ill patients.