Assessment of Changes in Abdominal Fat
Condition: Obesity
Study type: Observational

Summary: 
      In this study, we propose to determine the effect of weight loss on amount of body fat, and
      on body fat distribution, in severely obese patients. We also want to determine what
      measurements (waist, hip or thigh circumference) best show the changes in body fat and fat
      distribution in this group. Most importantly, we want to relate the changes in body
      measurements to changes in health indicators (blood cholesterol, blood pressure, blood
      sugars, liver function). With the findings of this study, clinicians should be able to
      predict an improvement in health based on a change in waist, hip or thigh size. Because this
      is a pilot study, we will focus on women, who make up the bulk of our clinic population. We
      will also focus on racial differences between Caucasians and Blacks.
    

Detailed description: 
      Severe obesity affects 4.7% of the U.S. population. A significant number of these individuals
      suffer from impaired glucose tolerance and type II diabetes due to insulin resistance (IR).
      Although it is generally accepted that the accumulation of intraabdominal (IA) fat increases
      the risk of developing IR, the mechanisms responsible for this phenomenon are not yet
      understood. In addition, the role of subcutaneous (SC) fat towards the etiology of IR -
      protective, inert or detrimental - is still under debate. This is because SC adipose tissue
      releases adipocytokines (IL-6, leptin, TNF-a) that have been demonstrated to impair insulin
      action. In individuals who are severely obese, hyperinsulinemia may induce an exaggerated
      production of adipocytokines from IA compared to SC fat stores. Our specific aims are: (1) to
      determine relative contribution of abdominal SC fat versus IA fat to systemic levels of IL-6,
      leptin and TNF-a in lean and in severely obese individuals; (2) to determine the effects of
      systemic adipocytokine concentrations on whole body as well as tissue sensitivity to insulin.
      Hypothesis: (a) In the context of severe obesity, IA fat produces increased quantities of
      IL-6, leptin and TNF-a compared to SC fat; (b) In severely obese patients undergoing weight
      loss, whole body and tissue IR can be predicted by changes in systemic adipocytokines.
      Methods: Adipose tissue content of IL-6, leptin and TNF-a will be determined by ELISA in
      biopsies obtained from IA and SC fat stores in lean and severely obese patients. Computer
      tomography-determined areas of IA and SC fat will be related to changes in systemic
      adipocytokines at baseline and 6-mo following weight loss therapy. Changes in systemic IL-6,
      leptin and TNF-a will be assessed from measurements made at baseline and following 6-mo
      weight loss. For this time period we will also determine changes in whole body (via IVGTT)
      and tissue sensitivity to insulin (via glucose uptake into muscle and fat). Relationships
      between systemic adipocytokines and IR will be assessed using uni- and multivariate
      correlation analysis. These novel studies will determine whether hypersecretion of
      adipocytokines by IA versus SC adipose tissue induces IR in patients with severe obesity.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Severely obese volunteers who are undergoing bariatric surgery. Subjects will be recruited
        from patients who are undergoing bariatric surgery procedures at Emory Bariatrics. The
        costs of surgical procedures are not provided by the research study.
      
Keywords: diabetes; insulin resistance