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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA155626-04
Application #
8715334
Study Section
Special Emphasis Panel (ZCA1-SRLB-4)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
4
Fiscal Year
2014
Total Cost
$401,075
Indirect Cost
$41,237
Name
Harvard University
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Malik, Vasanti S; Li, Yanping; Tobias, Deirdre K et al. (2016) Dietary Protein Intake and Risk of Type 2 Diabetes in US Men and Women. Am J Epidemiol 183:715-28
Hruby, Adela; Manson, JoAnn E; Qi, Lu et al. (2016) Determinants and Consequences of Obesity. Am J Public Health 106:1656-62
Global BMI Mortality Collaboration (2016) Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet 388:776-86
Cespedes, Elizabeth M; Bhupathiraju, Shilpa N; Li, Yanping et al. (2016) Long-term changes in sleep duration, energy balance and risk of type 2 diabetes. Diabetologia 59:101-9
James, Peter; Jankowska, Marta; Marx, Christine et al. (2016) ""Spatial Energetics"": Integrating Data From GPS, Accelerometry, and GIS to Address Obesity and Inactivity. Am J Prev Med 51:792-800
Schmitz, Kathryn H; Gehlert, Sarah; Patterson, Ruth E et al. (2016) TREC to WHERE? Transdisciplinary Research on Energetics and Cancer. Clin Cancer Res 22:1565-71
Song, Mingyang; Hu, Frank B; Spiegelman, Donna et al. (2016) Long-term status and change of body fat distribution, and risk of colorectal cancer: a prospective cohort study. Int J Epidemiol 45:871-83
Birmann, Brenda M; Barnard, Mollie E; Bertrand, Kimberly A et al. (2016) Nurses' Health Study Contributions on the Epidemiology of Less Common Cancers: Endometrial, Ovarian, Pancreatic, and Hematologic. Am J Public Health 106:1608-15
Song, Mingyang; Mehta, Raaj S; Wu, Kana et al. (2016) Plasma Inflammatory Markers and Risk of Advanced Colorectal Adenoma in Women. Cancer Prev Res (Phila) 9:27-34
Huang, Ru-Yi; Huang, Chuan-Chin; Hu, Frank B et al. (2016) Vegetarian Diets and Weight Reduction: a Meta-Analysis of Randomized Controlled Trials. J Gen Intern Med 31:109-16

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