Exercise and Metformin to Impact Hyperinsulinemia in Colorectal Cancer Survivors

运动和二甲双胍对结直肠癌幸存者高胰岛素血症的影响

• 批准号: 8072431
• 负责人: JEFFREY A MEYERHARDT
• 金额: $ 38.91万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-28 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8072431
• 关键词: 5' -AMP-activated protein kinase; Acromegaly; Aerobic Exercise; Attention; Behavior; Behavioral; Biological Markers; Body Composition; Body Weight; C-Peptide; Cancer Center; Cancer Patient; Cancer Survivor; Colon Carcinoma; Colorectal Cancer; Data; Diabetes Mellitus; Diagnosis; Diet; Disease; Exercise; Exercise stress test; Fasting; Hormones; Hyperinsulinism; Incidence; Individual; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Intervention; Metformin; Observational Study; Pathway interactions; Patients; Placebos; Planning Theory; Randomized; Reporting; Research; Risk; Role; Somatomedins; Staging; Techniques; Testing; Training; United States; cancer prevention; cancer recurrence; cancer risk; cancer therapy; energy balance; human FRAP1 protein; improved; inflammatory marker; mortality; outcome forecast; randomized trial; tumorigenesis

Project 4: Exercise and Metformin to Impact Hyperinsulinemia in Colorectal Cancer Survivors Summary Observational evidence suggests that factors related to energy balance, including exercise, body weight and diet, may be related not only to the risk of developing colorectal cancer, but also to prognosis in patients who develop the disease. One hypothesis for the impact of these factors on colorectal cancer tumorigenesis and prognosis is related to hyperinsulinemia and insulin-like growth factors. Several studies have demonstrated that colon cancer risk and recurrence rates are elevated in individuals with higher circulating levels of insulin or C-peptide as well as in individuals with higher levels of insulin-like growth factor (IGF)-I or lower levels of IGF binding protein (IGFBP)-3. However, there are no data testing strategies to lower levels of insulin or related hormones in colorectal cancer survivors. Two strategies that have strong scientific rationale to impact on the insulin-related pathways are exercise intervention and metformin. Exercise has consistently been shown in observational studies to reduce the hsk of developing colorectal cancer and, more recently, risk of cancer recurrence and colorectal-cancer related mortality. Metformin reduces hyperinsulinemia and activates the AMP-activated protein kinase (AMPK) which suppresses a variety of pathways. In project 4, we propose a 2 x 2 randomized trial of supervised aerobic exercise guided by validated behavioral support techniques versus attention control and metformin versus placebo in stage l - l l l colorectal cancer patients within 2 years of completion of therapy. The primary objective will be to determine whether supervised exercise training alone and metformin, either alone or in combination, can decrease fasting insulin level from baseline to 6 months in patients who completed standard therapy for stage I - III colorectal cancer. Secondary objectives include (1) comparing changes in other insulin-related biomarkers, (2) explore for an interaction effect in addition to an additive effect of exercise and metformin in reducing fasting insulin level over the 6 month intervention, (3) compare changes in body composition as well as self-directed change in diet quality, (4) compare changes in pro-inflammatory markers related to insulin resistance, (5) determine whether the theoretical constructs of the theory of planned behavior predict change in exercise behavior.

项目4：运动和二甲双胍影响大肠癌幸存者中高胰岛素血症 概括 观察性证据表明，与能量平衡有关的因素，包括运动，体重和饮食，不仅与患结直肠癌的风险有关，而且与患上这种疾病的患者的预后有关。这些因素对结直肠癌肿瘤发生和预后的影响的假设与高胰岛素血症和胰岛素样生长因子有关。几项研究表明 在具有较高循环水平的胰岛素或C肽以及具有较高水平的胰岛素样生长因子（IGF）-I或较低水平的IGF结合蛋白（IGFBP）的个体中，结肠癌的风险和复发率升高，以及具有较高水平的胰岛素样生长因子（IGF）的个体中的个体升高。 -3。但是，没有数据测试策略可以降低结直肠癌幸存者中胰岛素或相关激素的水平。两种具有强烈科学原理的策略，以影响 胰岛素相关的途径是运动干预和二甲双胍。在观察性研究中始终显示了运动，以减少发生大肠癌的HSK，并在最近发生癌症复发和大肠癌相关死亡率的风险。二甲双胍可降低高胰岛素血症并激活AMP激活的蛋白激酶（AMPK），该蛋白激酶（AMPK）抑制了多种途径。在项目4中，我们提出了一项2 x 2的监督有氧运动的随机试验，这些试验是由经过验证的行为支持技术与注意力控制和二甲双胍与安慰剂与安慰剂相比，在治疗完成后的2年内。主要目标是确定单独监督运动训练和二甲双胍是否单独或合并，可以降低禁食胰岛素水平，从基线到6个月 为I -III期结肠癌完成标准疗法的患者。次要目标包括（1）比较其他与胰岛素相关的生物标志物的变化，（2）探索互动效应外，还可以在6个月内降低禁食胰岛素水平的锻炼和二甲双胍的添加效果，（3）比较身体成分以及饮食质量的自我变化，（4）比较 与胰岛素抵抗有关的促炎标记物，（5）确定计划行为理论的理论结构是否预测了运动行为的变化。