GLUCOSE METABOLISM AND HYDRAZINE IN CANCER CACHEXIA

体重减轻通常伴随着癌症，并与穷人有关。 临床结果。 仅提供热量在很大程度上是不成功的， 改变这种预测。 我们和其他人已经证明， 糖尿病患者体内葡萄糖生成率和葡萄糖耐受不良 与年龄匹配的对照组相比，晚期癌症。 我们还展示了一个 一项随机试验表明，硫酸肼，一种已知的 在动物体内的糖异生，有利地影响了异常的葡萄糖 减肥癌症患者的新陈代谢。 在我们的研究中， 葡萄糖代谢的改善与体重维持相关， 接受短期肼治疗的患者。 在拟议的研究中， 硫酸肼影响不良临床结局的能力， 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研究中评估， 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， 代谢、营养和临床参数。 葡萄糖产生和 还使用组合的UC-14和6 H-3葡萄糖输注进行葡萄糖再循环 因为将测定葡萄糖反调节激素。 胰岛素 将定义与硫酸肼相关的灵敏度改变 使用Bergman最小模型和高胰岛素正葡萄糖钳夹 技术. 将评估静息能量消耗。 身体成分 （通过人体测量、H-3水测定和CT扫描）和肿瘤 将测量质量。 然后患者将接受明确的化疗 结肠癌和非小细胞肺癌的治疗 每日口服肼。 所有住院检查程序将 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 与肼使用相关的变化。 因此， 硫酸肼影响营养和临床结果 逆转葡萄糖代谢异常将在两个 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.