Altered insulin response to glucose in weight-losing cancer patients

Cancer cachexia and the underlying metabolic disturbances are due in part to either altered insulin release and action. Glucose intolerance in cancer patients is frequently observed but the nature of the insulin response is not usually described. The aim of this study was to investigate the insulin response in fasted, weigh-losing cancer patients following an oral glucose load (75 g). All cancer patients (n = 35) showed glucose intolerance. Three types of response were identified; those with an increased insulin: glucose ratio (I:G) at 60 min, (average 12.3, n = 13), those with a normal I:G (average 7.2 n = 7) and those with a decrease I:G (average 4.2, n = 15). Fasting plasma glucose concentrations were normal in all groups prior to the glucose tolerance test. However, patients with the lowest I:G also had the lowest fasting plasma insulin concentrations, the lowest plasma albumin concentrations and the highest plasma triglyceride concentrations. Those patients with an abnormal insulin response (either high or low I:G) had significantly greater weight loss (16% for low I:G group, 13% for the high I:G) compared to the normal responders (8%). Plasma fatty acid concentrations were increased in all cancer patients and decreased appropriately after glucose administration, indicating that lipolysis remained sensitive to the action of insulin. It is concluded that weight loss in cancer is associated with glucose intolerance and an abnormal insulin response, and that this response is indicative of either insulin resistance (high I:G) or decreased pancreatic function (low I:G). These findings suggest a role for insulin replacement therapy in the latter group of patients.