GLUCOSE METABOLISM AND HYDRAZINE IN CANCER CACHEXIA

体重减轻通常伴随着癌症，并与贫穷有关 临床结果。仅靠提供卡路里在很大程度上是不成功的 改变这一预后。我们和其他人已经证明了 糖尿病患者体内葡萄糖生成率与糖耐量异常的关系 晚期癌症与年龄匹配的对照组相比。我们还在一个 一项随机试验，已知的一种抑制剂硫酸肼 在动物中的糖异生，有利于影响异常的血糖 减肥癌症患者的新陈代谢也是如此。在我们的研究中， 糖代谢的改善与体重的维持有关 接受短期联氨治疗的患者。在拟议的研究中， 硫酸肼对不良临床结局及预后的影响 晚期非小细胞肺癌患者的营养状况 结肠腺癌将在两个前瞻性的评估， 双盲、安慰剂对照、随机临床试验。所有患者 将在代谢病房条件下进行初步研究以量化 代谢、营养和临床参数。葡萄糖的产生和 联合输注UC-14和6H-3葡萄糖回收葡萄糖 作为葡萄糖的反向调节激素将被测定。胰岛素 将定义与硫酸肼相关的敏感性改变 应用Bergman最小模型和高胰岛素正常血糖钳夹 技巧。将评估静息能量消耗。身体成分 (不包括人体测量、H-3水测定和CT扫描)和肿瘤 质量将被测量。然后，患者将接受明确的化疗 联合或不联合化疗治疗结肠癌和非小细胞肺癌 每日补充口服联氨。所有住院检测程序都将 在治疗4周和12周后重复。营养状况的变化， 能量消耗和临床结果将与代谢相关 与联氨使用相关的变化。其结果是， 硫酸肼通过以下方式影响营养和临床结局 逆转葡萄糖代谢异常的评估将分两个阶段进行 癌症患者群体。

Weight loss commonly accompanies cancer and is associated with a poor clinical outcome. Caloric provision alone has been largely unsuccessful in altering this prognosis. We and others have demonstrated increased whole body glucose production rates and glucose intolerance in patients with advanced cancer compared to age-matched controls. We have also shown in a randomized trial that hydrazine sulfate, a known inhibitor of gluconeogenesis in animals, favorably influences the abnormal glucose metabolism in weight losing cancer patients as well. In our studies, improvement in glucose metabolism was associated with weight maintenance in patients given short term hydrazine treatment. In the proposed studies, the ability of hydrazine sulfate to influence the poor clinical outcome and nutritional status of patients with advanced non-small cell lung cancer and adenocarcinoma of the colon will be assessed in two prospective, double-blind, placebo-controlled, randomized clinical trials. All patients will be initially studied under metabolic ward conditions to quantitate metabolic, nutritional and clinical parameters. Glucose production and glucose recycling using combined UC-14 and 6H-3 glucose infusions as well as glucose counter-regulatory hormones will be determined. Insulin sensitivity alteration associated with hydrazine sulfate will be defined using the Bergman minimal model and hyperinsulinemic euglycemic clamp techniques. Resting energy expenditure will be assessed. Body composition (unsing anthropometrics, H-3 water determination and CT scanning) and tumor mass will be measured. Patients will then receive defined chemotherapy treatment for colon and non-small cell lung cancer with or without the addition of daily oral hydrazine. All inpatient testing procedures will be repeated after 4 and 12 weeks of therapy. Changes in nutritional status, energy expenditure and clinical outcome will be correlated with metabolic changes associated with hydrazine use. As a result, the ability of hydrazine sulfate to influence nutritional and clinical outcome by reversing abnormalities in glucose metabolism will be assessed in two cancer patient populations.