Effects of ATP infusion on glucose turnover and gluconeogenesis in patients with advanced non-small-cell lung cancer Available to Purchase

Cancer cachexia is associated with elevated lipolysis, proteolysis and gluconeogenesis. ATP infusion has been found to significantly inhibit loss of body weight, fat mass and fat-free mass in patients with advanced lung cancer. The present study was aimed at exploring the effects of ATP on whole-body glucose turnover, alanine turnover and gluconeogenesis from alanine. Twelve patients with advanced non-small-cell lung cancer (NSCLC) were studied 1 week before and during 22–24 h of continuous ATP infusion. After an overnight fast, turnover rates of glucose and alanine, and gluconeogenesis from alanine, were determined using primed constant infusions of [6,6-²H₂]glucose and [3-¹³C]alanine. Thirteen NSCLC patients and eleven healthy subjects were studied as control groups without ATP infusion. During high-dose ATP infusion (75 µg·min^-1·kg^-1), glucose turnover was 0.62±0.07 mmol·h^-1·kg^-1, compared with 0.44±0.13 mmol·h^-1·kg^-1 at baseline (P = 0.04). For gluconeogenesis a similar, but non-significant, trend was observed [baseline, 0.30±0.16 mmol·h^-1·kg^-1; during ATP, 0.37±0.13 mmol·h^-1·kg^-1 (P = 0.08)]. At lower ATP doses (37–50 µg·min^-1·kg^-1) these effects were not detected. The relative increase in glucose turnover during ATP infusion compared with baseline showed a significant correlation with the ATP dose (r = 0.58, P = 0.02). No change in alanine turnover was observed at any ATP dose. The results of this study indicate an increase in glucose turnover during high-dose ATP infusion compared with baseline levels. During high-dose ATP infusion, glucose turnover was similar to that during low-dose ATP infusion and to that in control NSCLC patients. Between ATP infusions, however, glucose turnover in patients treated with high-dose ATP was significantly lower than that in the low-dose and control NSCLC patients (P = 0.04 and P = 0.03 respectively), and similar to that in healthy subjects. This would suggest that repeated high-dose ATP infusions may inhibit glucose turnover between infusion periods.