Oxidative stress, an imbalance between reactive molecular species and antioxidant defenses, has been associated with obesity, inflammation, and diabetes in mostly cross-sectional studies. Obesity is a well recognized risk factor for type 2 diabetes. Several proteins and inflammatory cytokines (adipocytokines) released from adipose tissue provide a possible link between obesity and diabetes. Since obesity is a chronic inflammatory state, oxidative stress may be a mediating factor between adiposity, inflammation, and diabetes.
We aim to examine whether markers of oxidative stress, inflammation, and adipocytokines mediate the association between obesity and insulin resistance and future diabetes. We propose to use existing data and stored plasma specimens from the Health, Aging, and Body Composition study, a 5-year prospective cohort study of well-functioning black and white older adults. We propose to measure F2-isoprostane and nitrotyrosine levels, reliable markers of lipid oxidative and protein nitrative stress respectively, using a nested case-control study design. We will also examine a previously assayed oxidative stress marker, oxidized LDL- cholesterol, and five existing inflammatory markers and adipocytokines for these analyses. The three oxidative stress markers provide distinct information about oxidative stress damage. We hypothesize that (1) oxidative stress measures, inflammatory markers, and adipocytokines will be independently associated with incident diabetes in individual and combined analyses; (2) oxidative stress measures, inflammatory markers, and adipocytokines will mediate the association between obesity and incident diabetes; (3) oxidative stress markers will be correlated with adipocytokines, and higher levels of inflammation and adipocytokines will modify the effect of oxidative stress on diabetes. If obesity is associated with increased oxidative stress, and oxidative stress lies in the causal pathway between obesity and type 2 diabetes, this may lead to future studies of therapeutic interventions to decrease diabetes in obese individuals. This purpose of this study is to understand whether several newly discovered biological markers provide the links between obesity and diabetes onset. If these markers are implicated in causing diabetes, then this would lead to testing whether vitamins or other supplements that target these markers may decrease the risk of diabetes in obese individuals. ? ?
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