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Treating hyperglycemia improves skeletal muscle protein metabolism in cancer patients after major surgery

Objective:Cancer and surgical stress interact to aggravate insulin resistance, protein catabolism, and glutamine depletion in skeletal muscle. We compared the effects of insulin-mediated euglycemia and moderate hyperglycemia on kinetics of protein and selected amino acids in skeletal muscle of female cancer patients after major surgery. Design:In each patient, a 24-hr period of insulin-mediated tight euglycemia (mean blood glucose, 5.8 ± 0.4 mmol/L) preceded or followed a 24-hr control period of moderate hyperglycemia (mean blood glucose, 9.6 ± 0.6 mmol/L) on the first and second day after surgery, in randomized order, according to a crossover experimental design. Setting:Intensive care unit, cancer hospital. Patients:Cancer patients after abdominal radical surgery combined with intraoperative radiation therapy. Interventions:Intensive (57 ± 11 units/24 hrs) and conventional (25 ± 5 units/24 hrs) insulin treatment during total parenteral nutrition. Measurements and Main Results:Muscle metabolism was assessed at the end of each 24-hr period of euglycemia and of hyperglycemia by leg arteriovenous catheterization with stable isotopic tracers. We found that euglycemia as compared with hyperglycemia was associated with higher (p < .05) fractional glucose uptake (16% ± 4% vs. 9% ± 3%); higher (p < .05) muscle protein synthesis and neutral net protein balance (−3 ± 3 vs. −11 ± 3 nmol phenylalanine·100 mL−1·min−1, respectively); lower (−52% ± 12%, p < .01) muscle nonprotein leucine disposal (an index of leucine oxidation) and higher (p < .05) plasma leucine concentrations; and higher (3.6 ± 1.7 times, p < .01) net de novo muscle glutamine synthesis and plasma glutamine concentrations (p < .05). Euglycemia was associated with higher (23% ± 7%, p < .05) plasma concentrations of arginine but did not affect either arginine release from muscle or plasma concentration and muscle flux of asymmetrical dimethylarginine. Rate of muscle proteolysis correlated (p < .05) with muscle release of asymmetrical dimethylarginine. Conclusions:Treating hyperglycemia improves skeletal muscle protein and amino acid metabolism in cancer patients after major surgery.