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.


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.
Biolo
Gianni
G
Division of Internal Medicine, Department of Clinical, Morphological and Technological Sciences, University of Trieste, Trieste, Italy. biolo@units.it
De Cicco
Marcello
M
Lorenzon
Stefania
S
Dal Mas
Viviana
V
Fantin
Dario
D
Paroni
Rita
R
Barazzoni
Rocco
R
Zanetti
Michela
M
Iapichino
Gaetano
G
Guarnieri
Gianfranco
G
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
D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D009124:Muscle Proteins; C487735:dimethylarginine; D005973:Glutamine; D010649:Phenylalanine; D001120:Arginine; D007930:Leucine