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Background: Surgical injury provokes a stress response that is thought to be pronounced in patients with diabetes mellitus type 2 (DM2) leading to intensified catabolism. The aim of this study was to compare the effects of perioperative epidural analgesia (EDA) versus patient controlled analgesia (PCA) and amino acid infusion on postoperative metabolism in patients with and without DM2., Methods: For this study, 12 nondiabetic patients and 12 diabetic patients undergoing colorectal surgery were randomly assigned to 4 groups (n = 6 per group) receiving either EDA (nondiabetic EDA and diabetic EDA [DEDA group]) or PCA with morphine (nondiabetic PCA and diabetic PCA) for perioperative pain control. Protein and glucose kinetics were measured on the second postoperative day using L-[1-13C]leucine and [6,6-2H2]glucose infusion during a fasted state and a 3-hr fed state with amino acid infusion., Results: The transition from the fasted to fed state suppressed endogenous rate of appearance (Ra) of glucose (P G 0.001) with a distinct effect for the DEDA group (P G 0.001). The Ra of leucine and the endogenous rate of appearance of leucine tended to be lower in the DEDA group(P = 0.056 and P = 0.07). Leucine oxidation was more suppressed in the DEDA group (P = 0.02) and when receiving amino acids(P = 0.001). Diabetic patients achieved a higher protein balance than nondiabetic patients (P = 0.032) and when receiving EDA instead of PCA (P = 0.012) or infusion of amino acids (P = 0.014)., Conclusions: A short-term infusion of amino acids reduced protein breakdown, increased protein synthesis, and rendered protein balance positive. This anabolic effect was pronounced in diabetic patients with EDA compared with nondiabetic patients or PCA, respectively, and prevented an undesirable hyperglycemia.