The long-term goal of the proposed PI, Dr. Yiqing Song, is to investigate the interrelationships among nutrient metabolisms, genetic variants, metabolic biomarkers, and risk of type 2 diabetes mellitus (DM) in epidemiologic studies. Through collaboration with his mentors at Brigham and Women's Hospital, the PI will develop expertise in all aspects of population genetic research needed for this project including genetic statistics and bioinformatics. Adequate intake of magnesium, an essential nutrient, is important in maintaining insulin and glucose homeostasis in the human body. There is also growing evidence, mostly from experimental studies, for a genetic basis of magnesium absorption and transport. This proposed research project will have two primary goals. First, this study will extend the applicant's previous epidemiologic research to examine the interrelationships between magnesium intake and biomarkers of systemic inflammation and lipid and lipoprotein metabolism in the Women's Health Study (WHS), a large prospective cohort with archived bio-specimens and detailed information on lifestyle factors and some biochemical markers. Second, the proposed genetic research will examine common genetic variants in seven genes involved in the magnesium homeostasis pathway in relation to the risk of type 2 DM in two prospective case-control studies nested in two large cohorts, the WHS (600 incident type 2 DM cases and 600 matched controls) and the Health Professionals Follow-up Study (HPFS) cohorts (1000 cases and 1000 matched controls). In addition to the primary goals, the proposed study will assess whether magnesium intake interacts with these genetic variants to modify risk of type 2 DM and will also apply several exploratory analytic approaches to explore the complex gene-gene and gene-environment interactions on type 2 DM risk. This proposal will enable the PI to develop the skills to launch his career as an independent investigator focusing on diabetes epidemiology. The proposed research project will provide a unique and comprehensive approach to better understand the mechanisms underlying the role of magnesium homeostasis in diabetes etiology, to help identify high-risk individuals, and to suggest new and more individualized treatment and/or prevention strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DK078846-03
Application #
7782820
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2008-04-01
Project End
2011-09-30
Budget Start
2010-04-01
Budget End
2011-09-30
Support Year
3
Fiscal Year
2010
Total Cost
$136,350
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Song, Yan; Huang, Yen-Tsung; Song, Yiqing et al. (2015) Birthweight, mediating biomarkers and the development of type 2 diabetes later in life: a prospective study of multi-ethnic women. Diabetologia 58:1220-30
Song, Yiqing; Liu, Simin (2012) Magnesium for cardiovascular health: time for intervention. Am J Clin Nutr 95:269-70
Goto, Atsushi; Song, Yiqing; Chen, Brian H et al. (2011) Coffee and caffeine consumption in relation to sex hormone-binding globulin and risk of type 2 diabetes in postmenopausal women. Diabetes 60:269-75
Chacko, Sara A; Sul, James; Song, Yiqing et al. (2011) Magnesium supplementation, metabolic and inflammatory markers, and global genomic and proteomic profiling: a randomized, double-blind, controlled, crossover trial in overweight individuals. Am J Clin Nutr 93:463-73
Song, Yiqing; Xu, Qun; Park, Yikyung et al. (2011) Multivitamins, individual vitamin and mineral supplements, and risk of diabetes among older U.S. adults. Diabetes Care 34:108-14
Chan, Kei-Hang K; Song, Yiqing; Hsu, Yi-Hsiang et al. (2010) Common genetic variants in fatty acid-binding protein-4 (FABP4) and clinical diabetes risk in the Women's Health Initiative Observational Study. Obesity (Silver Spring) 18:1812-20
Chen, Brian H; Song, Yiqing; Ding, Eric L et al. (2010) Association of resistin promoter polymorphisms with plasma resistin levels and type 2 diabetes in women and men. Int J Mol Epidemiol Genet 1:167-74
Chacko, Sara A; Song, Yiqing; Nathan, Lauren et al. (2010) Relations of dietary magnesium intake to biomarkers of inflammation and endothelial dysfunction in an ethnically diverse cohort of postmenopausal women. Diabetes Care 33:304-10
Song, Yiqing; Klevak, Anna; Manson, Joann E et al. (2010) Asthma, chronic obstructive pulmonary disease, and type 2 diabetes in the Women's Health Study. Diabetes Res Clin Pract 90:365-71
Song, Yiqing; Cook, Nancy R; Albert, Christine M et al. (2009) Effect of homocysteine-lowering treatment with folic Acid and B vitamins on risk of type 2 diabetes in women: a randomized, controlled trial. Diabetes 58:1921-8

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