Cachexia of malignancy: potential role of insulin in nutritional management

Abstract

Patients manifesting the syndrome of cachexia of malignancy exhibit an abnormal diabetic glucose tolerance. In our patients this has been correlated with a marked resistance to administered insulin, while insulin receptors on monocytes are normal. Lipolysis remains responsive to the effects of insulin. The oxidation of FFA, as a substrate for metabolism, has been reported to be increased, and the utilization of glucose as a metabolic fuel is reduced. Increased Cori cycle activity has been demonstrated, which produces an enhanced gluconeogenesis from lactate and amino acids; there is an expenditure of 6 ATP for the synthesis of each mole of glucose. An attempt to interrupt the Cori cycle in man, using hydrazine sulfate to inhibit the enzyme phosphoenolpyruvate carboxykinase, has not resulted in reproducible clinical benefit. However, successful treatment of the underlying tumor may produce a total reversal of the cachexia syndrome, suggesting that neoplasms have the potential to elaborate an, as yet, unidentified metabolic toxin. The use of insulin to counteract the reported abnormalities should be examined as a possible supportive measure in the total nutritional management of the cancer patient.