Identifying individuals at high risk of developing type 2 diabetes (T2DM) is critical for effective targeted interventions. We propose to test the hypothesis that urinary F2- isoprostanes (F2-IsoPs) are a biomarker for the risk of T2DM. In a pilot study, we found that baseline levels of urinary F2-IsoPs are inversely associated with incident T2DM;after adjustment for age, body mass index, and impaired glucose tolerance (IGT)-status, the odds of T2DM was 0.32 (95% CI, 0.12-0.81). This association was similar in the normal (NGT) and IGT sub-groups: ORs were 0.23 and 0.34, respectively. Our data suggest that individuals with lower F2-IsoP levels prior to diagnosis have a 3-fold increased risk for developing T2DM. We published a hypothesis that explains these results and predicts that urinary F2-IsoPs are also inversely associated with the risks of IGT and weight gain. We propose to expand our pilot study to the entire eligible IRAS cohort (n=900). Our primary specific aim is to test the hypothesis that urinary F2-IsoPs are inversely associated with the risk of T2DM. The secondary specific aims are to assess prospective associations between F2-IsoPs and two outcomes: IGT and weight gain. Urinary levels of F2-IsoPs will be measured by a recently developed, high-throughput UPLC-MS/MS method. The proposed research offers an important opportunity to develop a new non- invasive biomarker, urinary F2-IsoPs, which has the potential to predict the risks of diabetes (beyond the known risk factors) and of weight gain, an outcome for which no biomarker is available.

Public Health Relevance

Type 2 diabetes is becoming a global epidemic with devastating consequences. Prevention of this disease is possible through lifestyle and pharmacological interventions. Therefore, there is an intensive effort to identify people at high risk. The proposed research offers an opportunity to develop a new biomarker, urinary levels of F2-IsoPs, which has the potential to predict the risk of diabetes beyond the known risk factors. Importantly, this biomarker is non-invasive and can be used in a clinical setting. We also believe that this biomarker can be used to predict weight gain, a very important characteristic for which no biomarkers are available.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK081028-02
Application #
7761765
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Staten, Myrlene A
Project Start
2009-02-01
Project End
2012-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
2
Fiscal Year
2010
Total Cost
$259,628
Indirect Cost
Name
Duke University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Il'yasova, Dora; Wagenknecht, Lynne E; Spasojevic, Ivan et al. (2015) Urinary F2-isoprostanes and metabolic markers of fat oxidation. Oxid Med Cell Longev 2015:729191
Siamakpour-Reihani, Sharareh; Scarbrough, Peter M; Wang, Frances et al. (2012) Systemic markers of oxidative status and colorectal adenomatous polyps. Ann Epidemiol 22:587-91
Il'yasova, Dora; Wang, Frances; Spasojevic, Ivan et al. (2012) Racial differences in urinary F2-isoprostane levels and the cross-sectional association with BMI. Obesity (Silver Spring) 20:2147-50
Il'yasova, Dora; Scarbrough, Peter; Spasojevic, Ivan (2012) Urinary biomarkers of oxidative status. Clin Chim Acta 413:1446-53
Il'yasova, Dora; Spasojevic, Ivan; Base, Karel et al. (2012) Urinary F2-isoprostanes as a biomarker of reduced risk of type 2 diabetes. Diabetes Care 35:173-4
Tolun, Adviye A; Scarbrough, Peter M; Zhang, Haoyue et al. (2012) Systemic oxidative stress, as measured by urinary allantoin and F(2)-isoprostanes, is not increased in Down syndrome. Ann Epidemiol 22:892-4
Il'yasova, Dora; Wang, Frances; Spasojevic, Ivan et al. (2012) Urinary F2-isoprostanes, obesity, and weight gain in the IRAS cohort. Obesity (Silver Spring) 20:1915-21
Soubry, Adelheid; Il'yasova, Dora; Sedjo, Rebecca et al. (2012) Increase in circulating levels of IGF-1 and IGF-1/IGFBP-3 molar ratio over a decade is associated with colorectal adenomatous polyps. Int J Cancer 131:512-7
Il'yasova, Dora; Kennedy, Kelly; Spasojevic, Ivan et al. (2011) Individual responses to chemotherapy-induced oxidative stress. Breast Cancer Res Treat 125:583-9
Il'yasova, Dora; Spasojevic, Ivan; Wang, Frances et al. (2010) Urinary biomarkers of oxidative status in a clinical model of oxidative assault. Cancer Epidemiol Biomarkers Prev 19:1506-10

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