Context: It has been difficult to distinguish the independent effects of caloric restriction versus exercise training on insulin resistance.

Objective: Utilizing metabolic feeding and supervised exercise training, we examined the influence of caloric restriction vs. exercise training with and without weight loss on hepatic and peripheral insulin resistance.

Design, Participants, and Intervention: Thirty-four obese, older subjects were randomized to: caloric restriction with weight loss (CR), exercise training with weight loss (EWL), exercise training without weight loss (EX), or controls. Based on an equivalent caloric deficit in EWL and CR, we induced matched weight loss. Subjects in the EX group received caloric compensation. Combined with [6,6²H₂]glucose, an octreotide, glucagon, multistage insulin infusion was performed to determine suppression of glucose production (SGP) and insulin-stimulated glucose disposal (ISGD). Computed tomography scans were performed to assess changes in fat distribution.

Results: Body weight decreased similarly in EWL and CR, and did not change in EX and controls. The reduction in visceral fat was significantly greater in EWL (-71 ± 15 cm²) compared to CR and EX. The increase in SGP was also almost 3-fold greater (27 ± 2%) in EWL. EWL and CR promoted similar improvements in ISGD [+2.5 ± 0.4 and 2.4 ± 0.9 mg · kg fat-free mass (FFM)^-1 · min^-1], respectively.

Conclusions: EWL promoted the most significant reduction in visceral fat and the greatest improvement in SGP. Equivalent increases in ISGD were noted in EWL and CR, whereas EX provided a modest improvement. Based on our results, EWL promoted the optimal intervention-based changes in body fat distribution and systemic insulin resistance.