Impact of Weight Loss on Physical Function

We are proposing a trial to directly compare a high intensity weight loss protocol to a moderate intensity weight loss protocol to determine which leads to greater improvements in physical function in severely obese older adults. We are also interested in comparing the safety of the two approaches. If we can demonstrate effective weight reduction that happens with sufficient expediency and impact to improve physical functioning without increasing adverse events in severely obese older adults, a sizable percentage of the population would benefit and there would be significant reductions in disability resulting in cost savings for the healthcare system. This application specifically addresses objective 3 as detailed in the announcement of this pilot funding mechanism (Objective 3. To develop and reliably test in clinical or pre-clinical studies novel interventions which target adiposity, peripheral or central nervous system, vascular, body composition and/or musculoskeletal related factors for preventing the age-related decline in physical function and preventing or reversing the progression to disability). This application describes a pilot randomized, controlled trial designed to address the following aims: * Assess efficacy and safety of high intensity medical weight management in severely obese (= stage II BMI) older adults for functional outcomes (i.e., functional weight loss) compared to a moderate intensity weight loss intervention. * Determine if a potential dose response relationship exists between weight loss volume (primarily as excess fat) and improvements in several measures of physical function. * Identify changes in body composition (fat and lean including bone) that are associated with changes in physical function. * Identify biomarkers (specific focus on markers of inflammation) that provide potential mechanistic links between weight reduction and changes in physical function in severely obese older adults. Our primary hypothesis is that there is a greater improvement in physical function with a high intensity weight loss intervention compared to a moderate intensity intervention.