Effect of systemic insulin on protein kinetics in postoperative cancer patients.
BACKGROUND
Cancer cachexia is a significant cause of postoperative morbidity and mortality in patients with tumors of the upper gastrointestinal tract. Standard parenteral nutrition (TPN) has failed to alter this. The anabolic effect of insulin has been well documented, and its positive effect on protein economy in cancer patients has been recently demonstrated. This study examines the effect of high-dose insulin and parenteral nutrition on protein kinetics in postoperative cancer patients.


METHODS
Eleven patients underwent surgery for pancreatic, esophageal, or gastric carcinoma. Postoperatively, patients received standard TPN for 4 days (1 g/kg/day amino acids, 1,000 kcal/day dextrose, 100 g/day lipid), and hyperinsulinemic parenteral nutrition for 4 days (same as standard TPN plus 1.44 U/kg/day regular human insulin) in a crossover design. All patients received both treatments, and the order of treatment was determined randomly. Euglycemia was maintained during insulin infusion via a variable 30% dextrose infusion. Patients underwent protein metabolic studies after each treatment period and rates of whole body and skeletal muscle protein synthesis, breakdown, and net balance were determined by radioisotopic tracer methods using 14C-leucine and 3H-phenylalanine.


RESULTS
Compared with standard TPN (STD), hyperinsulinemic TPN (INS) resulted in a significant increase in skeletal muscle protein synthesis (INS: 52.04 +/- 10.22 versus STD: 26.06 +/- 6.71 nmol phe/100 g/min, p < 0.05) and net balance of protein (INS: 7.75 +/- 4.61 versus STD: -15.10 +/- 6.44 nmol phe/100 g/min, p < 0.01), but no difference in skeletal muscle protein breakdown (INS: 44.29 +/- 11.54 versus STD: 41.17 +/- 5.89 nmol phe/100 g/min). Whole-body net balance of protein also significantly increased with insulin-based TPN, compared with standard TPN (INS: 0.04 +/- 0.05 versus STD: -0.08 +/- 0.07 mumol leu/kg/min, p < 0.05), but no difference in whole-body protein synthesis (INS: 2.52 +/- 0.15 versus STD: 2.49 +/- 0.15 mumol leu/kg/min) or whole-body protein breakdown (INS: 2.48 +/- 0.16 versus STD: 2.58 +/- 0.19 mumol leu/kg/min) was observed. Patients received significantly more calories during the hyperinsulinemic TPN period than during the standard TPN period. There was no difference in total, essential, or branched-chain amino acids, and no difference in serum free fatty acids, triglycerides, or cholesterol was observed between the two treatment periods.


CONCLUSIONS
High-dose insulin in conjunction with hypercaloric parenteral nutrition causes improved skeletal muscle protein synthesis, skeletal muscle protein net balance, and whole-body protein net balance compared with standard TPN in postoperative cancer patients.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
D B
DB
Pearlstone
R F
RF
Wolf
R S
RS
Berman
M
M
Burt
M F
MF
Brennan
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000097:blood; D002100:Cachexia / Q000209:etiology / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000378:metabolism* / Q000601:surgery*; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009752:Nutritional Status; D010289:Parenteral Nutrition, Total / Q000379:methods; D011184:Postoperative Period; D011446:Prospective Studies; D014176:Protein Biosynthesis
D000596:Amino Acids; D007328:Insulin