Optimizing Body Composition for Function in Older Adults

The purpose of this pilot study is to compare two strategies intended to improve the health of overweight older adults by improving body composition. One strategy, resistance training, is designed to preserve skeletal muscle mass. The other strategy, the use of a PPAR-γ agonist, is designed to enhance the loss of fat from visceral and skeletal depots. These strategies will be used in conjunction with a hypocaloric diet and will be compared to a hypocaloric diet alone to determine if either of these strategies are superior in reducing visceral fat and preserving muscle mass.

In this pilot we propose to recruit 88 older (65 - 79 yrs) men (n=48) and women (n=40) at risk for disability and with indications for weight loss according to NIH guidelines. All will be enrolled in a dietary intervention designed to generate a caloric deficit of 500 kcal/day for a 4 month period. All will receive supplemental vitamin D and calcium. These participants will be randomized into one of 4 groups: Group 1 - Hypocaloric diet (and placebo) Group 2 - Hypocaloric diet and resistance training designed to maximize muscular power (and placebo) Group 3 - Hypocaloric diet and a PPAR- γ agonist (pioglitazone/Actos™) Group 4 - Hypocaloric diet and resistance training and pioglitazone/Actos™ The specific aims of the pilot are: In both men and women, to determine whether randomization to resistance exercise is associated with an increased retention of appendicular non-bone lean mass compared to those not undergoing power training. In both men and women, to determine whether randomization to the pioglitazone group is associated with an increased loss of visceral adiposity relative to randomization to the non-pioglitazone group. Assess the feasibility of the recruitment, assessment and intervention strategies To estimate adherence to the weight loss, exercise training, and drug interventions; In this population, to determine measurement characteristics of the functional outcomes that will be considered as primary end-points of the larger study. To obtain pilot data on a subset of participants to determine the feasibility, acceptability and measurement characteristics of muscle samples (biopsies) to quantify intramyocellular lipid in this study population.

Inclusion Criteria: Weight Stable, Indication for weight loss per NIH guidelines, Performance on the short physical performance battery score 3-10 Exclusion Criteria: Diabetes, weight > 136 kg, Medical condition that limits exercise participation, Congestive heart failure, abnormal kidney function, higher ALT than normal, currently involved in a weight loss or exercise program, current smoking, alcohol or drug abuse, taking anti-inflammatory steroids, taking protein supplements, taking PPAR-gamma agonist, edema, anemia