Whole-body protein metabolism in cancer-bearing patients. Effect of total parenteral nutrition and associated serum insulin response

Abstract

Aggressive nutritional support of the cancer patient undergoing treatment has become widespread standard practice. In order to evaluate the effect of total parenteral nutrition (TPN) on protein metabolism, 11 patients with localized squamous cell carcinoma of the distal esophagus were studied in the postabsorptive state and again after 2 weeks of TPN. After two weeks of TPN, these cancer patients demonstrated a significant increase in body weight associated with positive nitrogen balance and an insignificant increase in total body potassium (determined by whole body 40K scanning), a measure of lean body mass. Serum transferrin, ceruloplasmin, and total protein did not change significantly, whereas serum albumin decreased significantly (3.5 +/- 0.1 to 3.1 +/- 0.1 g dl-1). Evaluation of whole-body protein kinetics by constant infusion of 15N-glycine demonstrated a significant increase in protein flux (2.79 +/- 0.20 to 4.02 +/- 0.33 g protein kg-1 day-1). In the group as a whole, protein synthesis increased and catabolism decreased, but not significantly. Skeletal muscle protein catabolism, as measured by the rate of excretion of urinary 3-methylhistidine (mumol kg-1 day-1) decreased significantly after 2 weeks of TPN (2.5 +/- 0.1 to 1.9 +/- 0.2). A change from basal to stimulated (TPN) serum insulin level of 40 to 120 microU/ml was found to be associated with optimal changes in protein synthesis and skeletal muscle catabolism. Five patients fell within this optimal range of serum insulin, and demonstrated a significant increase in the rate of wholebody protein synthesis (2.13 +/- 0.35 to 3.56 +/- 0.45 g protein kg-1 day-1) with an insignificant increase in whole-body protein catabolism (2.74 +/- 0.42 to 3.16 +/- 0.43), and a significant decrease in urinary 3-methylhistidine excretion (2.50 +/- 0.35 to 1.53 +/- 0.24) after 2 weeks of TPN. It is concluded that optimum nutritional support with TPN is beneficial to the cancer patients' protein economy by stimulating whole body protein synthesis while decreasing skeletal muscle protein catabolism. It is also concluded that there exists a range of serum insulin in which whole-body protein synthesis and catabolism are optimized.