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

Crit Care Med. 2008 Jun;36(6):1768-75. doi: 10.1097/CCM.0b013e318174de32.

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.

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 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Neoplasms / radiotherapy
  • Abdominal Neoplasms / surgery*
  • Amino Acids / blood
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Blood Glucose / metabolism
  • Cancer Care Facilities
  • Combined Modality Therapy
  • Critical Care / methods*
  • Cross-Over Studies
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Female
  • Glutamine / blood
  • Humans
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / physiopathology
  • Insulin / therapeutic use*
  • Insulin Resistance / physiology
  • Leucine / blood
  • Middle Aged
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / physiopathology
  • Overweight / physiopathology
  • Parenteral Nutrition, Total
  • Phenylalanine / blood
  • Postoperative Complications / drug therapy*
  • Postoperative Complications / physiopathology
  • Radiotherapy, Adjuvant

Substances

  • Amino Acids
  • Blood Glucose
  • Insulin
  • Muscle Proteins
  • dimethylarginine
  • Glutamine
  • Phenylalanine
  • Arginine
  • Leucine