Insulin Resistance in Severely Obese Patients
Condition: Obesity; Insulin Resistance; Diabetes
MeSH terms: Insulin Resistance
Study type: Observational

Summary: 
      This study aims to understand the biological processes that link obesity to diseases
      including insulin resistance and diabetes. Our approach involves studying the health of
      patient undergoing weight loss either via weight reduction surgery or by medically supervised
      liquid formula diets. Patients must be enrolled in a weight treatment program at Emory
      Bariatrics, Emory University, Atlanta GA, to be eligible for this study. This study does not
      cover the cost of treatment at Emory Bariatrics. The hypothesis is that decreases in
      adipose-tissue derived factors during weight loss will be related to improvement in insulin
      function.
    

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- ) 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- 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- 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- 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- 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.
    

Time perspective: Prospective
Keywords: adipose tissue; adipocytokines