Comparative biomolecular and therapeutic effectiveness of collaborative integrative intervention in morbidly obese individuals

2012-09-19Background. Obesity is prevalent and linked with inflammation, insulin resistance, dyslipidemia, atherosclerosis, and associated with significant morbidity and mortality. The economic burden of obesity-related illnesses is substantial, with estimates ranging from 2% to 7% of the total US health care expenditures and billions of dollars in direct and indirect costs to society. This goal will be accomplished by collaborative integrative interventions (CI) in morbidly obese individuals in which eligible subjects will be randomized to MI plus Gastric bypass surgery (GBS), intense exercise and moderate caloric restriction (IE-MCR), or anti-obesity medications (AOM). ❧ Importance/Significance. There is a cumulative increase in the rate of obesity, up to two thirds of the US population. This randomized clinical trial will assess: 1) the change in biologic and clinical phenotypes in response to CI, 2) the change in genotypes in response to CI, and 3) Comparative biomolecular, therapeutic and cost effectiveness analyses of methods of CI to develop individualized intervention models to improve management of morbidly obese individuals. vascular function measured as coronary distensibility index (CDI), atherosclerotic burden measured as carotid intima media thickness (CIMT) and coronary plaque volume (CPV), metabolically active adipose tissue (MAC), oxidative stress and inflammatory biomarkers se well as changes in DNA methylation patterns, expression and regulation of promoter regions of genes provides fundamental information to assess the beneficial effects within and across CI methods on obesity management. This study investigates the underlying determinant of successful management of obesity by comparing biologic, clinical phenotype, genotype and cost effectiveness of CI methods, also enhances individualized anti-obesity interventions. ❧ Method. The CI methods are hypothesized to improve CDI and reduce CIMT, CPV and MAC, also increase up-regulation of cardio-protective genes. Over a 3 year period, 150 morbidly obese individuals’ ages 18 or older and free of clinical cardiovascular disease will be recruited from the Obesity Clinic of the Greater Los Angeles VA Health Care System, University of California Los Angeles and Cedars Sinai Medical Center. One hundred and fifty eligible subjects will be randomized to either of CI methods inclusive of MI plus GBS, IE-MCR, or AOM (50 in each group). All subjects will receive weekly MI training for a year. MI plus IE-MCR will receive lectures on exercise and general dietary measures including calorie counting. They will prepare their own food, with protien:carbohydrate:fat ratio of 30:45:25 and over 70% their resting daily energy expenditure, and completed daily food and exercise journals. They will exercise 3 ± 2 hours/day, about half supervised, for a year. MI plus GBS will undergo primary laparoscopic RYGB. MI plus AOB will receive xx pills daily for a period of 1-year. All subjects will be followed before, during and after interventions. Subjects will undergo carotid ultrasound and CT at baseline and at 1-year follow-up, also their oxidative stress and inflammatory biomarkers as well as genetic markers will be assessed. CI methods’ compliance and side effects will be evaluated