AS189 - Biochemical and anthropometric heterogeneity among morbid obese women in the Women's Health Initiative observational study

Investigator Names and Contact Information

Rachel Mackey (mackey@edc.pitt.edu)

Introduction/Intent

We propose to evaluate the distribution of adipokines and relationship to risk of coronary heart disease (CHD) in the Women’s Health Initiative Observational Study. The primary focus is on the morbidly obese group, body mass index (BMI) ≥40. We will measure adipokines, ghrelin, adiponectin and leptin as well as insulin and glucose in 350 black and 350 white women with BMI ≥40 and in 60 black and white women in the other five BMI categories (600 total). We also will do a case-control analysis of CHD risk within BMI ≥40 category. Other measures will include nuclear magnetic resonance spectroscopy of lipoproteins. This will be the first study in a well-defined, large sample to evaluate adipokines in relation to key risk factors and outcomes.

Specific Aims

1. To determine the distribution of specific adipokines: leptin, ghrelin, adiponectin as well as insulin, blood glucose, nuclear magnetic resonance (NMR) spectroscopy of lipoproteins, among morbidly obese women (body mass index [BMI] ≥40) in the Women’s Health Initiative Observational Study (WHI OS) in order to evaluate determinants of distribution of adipokines among morbidly obese in relation to selected risk factors and lipoprotein levels

• a. Levels of adipokines will be related to distribution of body fat, i.e. waist circumference.
• b. Levels of adiponectin will be higher in blacks than whites.
• c. Perimenopausal weight gain will be associated with lower adiponectin, higher leptin and lower ghrelin levels.
• d. Lower adiponectin, higher leptin and low ghrelin will be associated with higher LDL particles, small LDL and lower HDL particles and higher small HDLc.

2. Levels of adipokines will be directly related to the degree of obesity and will be substantially higher among morbidly obese women with BMI ≥40. The primary determinant of the adipokine levels will be insulin resistance, both across and within BMI categories: <20, 20-24, 25-29, 30-34, 35-39 and 40+. There will be a subset of women with low or normal levels of adipokines, even among women with BMI ≥40. These women will be characterized as being insulin sensitive, i.e. having relatively normal insulin and glucose levels and no history of diabetes. These women will also have a lower prevalence of hypertension, lower waist circumference, lower VLDL triglycerides, higher large HDL and lower levels of small LDL particles.

3. Levels of adipokines will be higher among morbidly obese women (BMI ≥40) who have developed incident coronary heart disease (CHD) during the WHI follow up as compared to non-incident CHD event participants, even after adjustment for age, race, degree of BMI or weight within this 40+ category, smoking, hypertension, waist circumference and diabetes.