EFFECT OF SYSTEMIC INSULIN ON PROTEIN KINETICS IN POSTOPERATIVE CANCER-PATIENTS

Background: Cancer cachexia is a significant cause of postoperative mo rbidity and mortality in patients with tumors of the upper gastrointes tinal tract. Standard parenteral nutrition (TPN) has failed to alter t his. The anabolic effect of insulin has been well documented, and its positive effect on protein economy in cancer patients has been recentl y demonstrated. This study examines the effect of high-dose insulin an d parenteral nutrition on protein kinetics in postoperative cancer pat ients. Methods: Eleven patients underwent surgery for pancreatic, esop hageal, or gastric carcinoma. Postoperatively, patients received stand ard TPN for 4 days (1 g/kg/day amino acids, 1,000 kcal/day dextrose, 1 00 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 c rossover 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 under went protein metabolic studies after each treatment period and rates o f whole body and skeletal muscle protein synthesis, breakdown, and net balance were determined by radioisotopic tracer methods using C-14-le ucine and H-3-phenylalanine. Results: Compared with standard TPN (STD) , hyperinsulinemic TPN (INS) resulted in a significant increase in ske letal 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 (IN S: 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-bo dy net balance of protein also significantly increased with insulin-ba sed 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-b ody protein synthesis (INS: 2.52 +/- 0. 15 versus STD: 2.49 +/- 0.15 m umol leu/kg/min) or whole-body protein breakdown (INS: 2.48 +/- 0.16 v ersus STD: 2.58 +/- 0.19 mumol leu/kg/min) was observed. Patients rece ived significantly more calories during the hyperinsulinemic TPN perio d than during the standard TPN period. There was no difference in tota l, essential, or branched-chain amino acids. and no difference in seru m free fatty acids . triglycerides, or cholesterol was observed betwee n the two treatment periods. Conclusion: High-dose insulin in conjunct ion with hypercaloric parenteral nutrition causes improved skeletal mu scle protein synthesis, skeletal muscle protein net balance, and whole -body protein net balance compared with standard TPN in postoperative cancer patients.