Biomarkers of Oxidative Stress in LOOK AHEAD - Ancillary to LOOK AHEAD
Condition: Heart Diseases; Myocardial Infarction; Obesity; Diabetes Mellitus, Non-insulin Dependent; Cardiovascular Diseases; Diabetes Mellitus
MeSH terms: Cardiovascular Diseases; Heart Diseases; Myocardial Infarction; Diabetes Mellitus; Diabetes Mellitus, Type 2; Infarction
Study type: Observational

Summary: 
      To determine how weight loss achieved by intensive lifestyle intervention including diet and
      exercise alters lipoprotein oxidation/oxidative stress and antioxidant status in overweight
      diabetic individuals.
    

Detailed description: 
      BACKGROUND:

      Overweight and diabetes increase risk of cardiovascular disease but the mechanism(s) that
      account for this effect remain to be clarified. Oxidation of low-density lipoprotein (LDL) is
      thought to contribute to atherosclerosis. Diabetes may increase oxidative stress, and this
      may contribute to increased risk of cardiovascular disease in diabetics. Caloric restriction
      and the initiation of exercise may increase oxidative stress in the short term and may thus
      adversely affect cardiovascular disease. Over the long term, metabolic adaptation may reduce
      oxidative stress. Such adaptation, together with beneficial changes in lipoprotein
      concentration, composition, and character, may allow expression of beneficial effects of
      weight loss on cardiovascular endpoints. However, the influence of weight loss on measures of
      lipoprotein oxidation/oxidative stress and antioxidant status in overweight diabetics has
      never been investigated.

      The study is ancillary to the Look AHEAD clinical trial which is sponsored primarily by the
      National Institute of Diabetes and Digestive and Kidney Diseases and secondarily by the
      National Heart, Lung, and Blood Institute, the National Institute of Nursing Research, the
      Office of Research on Women's Health, the National Center on Minority Health and Health
      Disparities, and the Centers for Disease Control and Prevention. The Look AHEAD study is a
      multicenter, randomized clinical trial to examine the long-term effects of a lifestyle
      intervention designed to achieve and maintain weight loss in overweight diabetics. The study
      is in response to an initiative on Ancillary Studies in Heart, Lung, and Blood Disease Trials
      released in June, 2000.

      DESIGN NARRATIVE:

      The primary aim of this project is to determine the influence of intensive lifestyle
      intervention on lipoprotein oxidation as assessed by autoantibodies to oxidized low-density
      lipoprotein. Other complementary indices of oxidative stress, and antioxidant status as
      assessed by circulating concentrations of lipophilic antioxidants, will be compared between
      lifestyle intervention and community care (control) arms of the Look AHEAD study. Such
      comparisons will be performed both early after intervention and later when metabolic
      adaptation is expected. By contrasting subgroups defined by differential compliance to diet
      or exercise, by gender, menopausal status, ethnicity, and age, secondary aims will consider
      whether changes in lipoprotein oxidation/oxidative stress and antioxidant status differ
      between such subgroups. Other aims will consider whether differences in lipoprotein
      oxidation/oxidative stress among the above subgroups can be accounted for by differences in
      lipoprotein concentration, composition, or character, carbohydrate metabolism, or antioxidant
      status. The results of this study will provide a potential mechanistic explanation for
      differences in cardiovascular endpoints between intervention and community care groups.