20578 Background: Cancer and surgical stress interact to aggravate insulin resistance, protein catabolism and glutamine depletion in skeletal muscle. In the clinical setting, hyperglycemia and glutamine depletion were associated with poor outcome in critically ill patients. The present study was designed to explore the effects of insulin mediated euglycemia and moderate hyperglycemia on kinetics of protein and selected amino acids in skeletal muscle of cancer patients after major surgery. Methods: Adult cancer patients were studied after abdominal radical surgery. In each patient a 24-h period of insulin-mediated tight euglycemia (mean blood glucose: 5.8± 0.4 mmol/l) preceded or followed a 24-h period of moderate hyperglycemia (mean blood glucose: 9.6± 0.6 mmol/l) on the first and the second day after surgery (cross-over design with randomized sequence of treatments). Intensive (57±11 U/24-h) or conventional (25±5 U/24-h) insulin treatments were used to obtain euglycemia or moderate hyperglycemia during total parenteral nutrition. Muscle metabolism was assessed at the end of each 24-h period of tight glycemic control and of hyperglycemia by leg arteriovenous catheterization with stable isotopic tracers. Results in the two different experimental conditions were compared using the Wilcoxon Matched-Pairs Signed-Ranks Test. P values < 0.05 were taken as significantly different. Results: Plasma insulin levels were not significantly different at the end of intensive or conventional insulin treatment period. Strict glycemic control as compared to hyperglycemia was associated with higher (p<0.05) fractional glucose uptake (16±4 vs 9±3 percent); higher (p<0.05) muscle protein synthesis and neutral net protein balance (-3±3 vs - 11±3 mmol PHE · 100cc-1 · min-1, respectively); higher (3.6±1.7 times, p<0.01) net de novo muscle glutamine production. Conclusions: This study shows that, in cancer patients after major surgery, hyperglycemia with relative insulin deficiency promotes muscle wasting and blunted the ability of muscle to provide glutamine to extra-muscular tissues. This latter effect could contribute to increased morbidity and mortality in surgical cancer patients with poor metabolic control. No significant financial relationships to disclose.