title: Treating hyperglycemia improves skeletal muscle protein metabolism in cancer patients after major surgery.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  Intensive care unit, cancer hospital.
  
  
  METHODS
  Cancer patients after abdominal radical surgery combined with intraoperative radiation therapy.
  
  
  METHODS
  Intensive (57 +/- 11 units/24 hrs) and conventional (25 +/- 5 units/24 hrs) insulin treatment during total parenteral nutrition.
  
  
  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 x 100 mL(-1) x 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.
authors.affiliation: Division of Internal Medicine, Department of Clinical, Morphological and Technological Sciences, University of Trieste, Trieste, Italy. biolo@units.it
authors.forename: Gianni
authors.initials: G
authors.lastname: Biolo
authors.forename: Marcello
authors.initials: M
authors.lastname: De Cicco
authors.forename: Stefania
authors.initials: S
authors.lastname: Lorenzon
authors.forename: Viviana
authors.initials: V
authors.lastname: Dal Mas
authors.forename: Dario
authors.initials: D
authors.lastname: Fantin
authors.forename: Rita
authors.initials: R
authors.lastname: Paroni
authors.forename: Rocco
authors.initials: R
authors.lastname: Barazzoni
authors.forename: Michela
authors.initials: M
authors.lastname: Zanetti
authors.forename: Gaetano
authors.initials: G
authors.lastname: Iapichino
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Guarnieri
mesh_terms: D000008:Abdominal Neoplasms / Q000532:radiotherapy / Q000601:surgery*; D000596:Amino Acids / Q000097:blood; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002173:Cancer Care Facilities; D003131:Combined Modality Therapy; D003422:Critical Care / Q000379:methods*; D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005260:Female; D005973:Glutamine / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000503:physiopathology; D007328:Insulin / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology; D007930:Leucine / Q000097:blood; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000503:physiopathology; D050177:Overweight / Q000503:physiopathology; D010289:Parenteral Nutrition, Total; D010649:Phenylalanine / Q000097:blood; D011183:Postoperative Complications / Q000188:drug therapy* / Q000503:physiopathology; D018714:Radiotherapy, Adjuvant
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D009124:Muscle Proteins; C487735:dimethylarginine; D005973:Glutamine; D010649:Phenylalanine; D001120:Arginine; D007930:Leucine