The impact of exercise training compared to caloric restriction on hepatic and peripheral insulin resistance in obesity.

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 [6,6(2)H(2)]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 cm(2)) 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 x kg fat-free mass (FFM)(-1) x 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.

Visceral fat and adiponectin: associations with insulin resistance are tissue-specific in women.

Body fatness and its distribution are strongly and independently associated with peripheral insulin action. However, these associations are limited in their ability to predict the independent nature of hepatic and peripheral insulin resistance, especially in obese women. To define the relationships more precisely between regional fat distribution and adiponectin, and hepatic and peripheral insulin resistance, we studied 22 obese (43 +/- 0.1%) women who underwent a dual-energy X-ray absorptiometry scan and a computed tomography scan at the L4-L5 level. An octreotide (60 ng x kg(-1) x min(-1)), glucagon (0.65 ng x kg(-1) x min(-1)), and two-step insulin (0.25 mU x kg(-1) x min(-1) and 1.0 mU x kg(-1) x min(-1)) infusion was performed to quantify insulin-mediated suppression of hepatic glucose production (SGP) and insulin-stimulated glucose disposal (ISGD) in a simultaneous fashion. Hepatic glucose production (HGP) was measured using a primed, constant infusion of [6,6(2)H(2)] glucose. Mean plasma insulin increased from 5.6 +/- 0.1 microU/mL at baseline to 15.1 +/- 1.5 microU/mL in the first stage, and to 80.7 +/- 0.5 microU/mL in the second stage. Although there was no significant relationship between visceral adipose tissue (VAT) and basal HGP (r = 0.34, p = 0.117), there was a significant inverse correlation (r = -0.67, p = 0.003) between VAT and SGP. There was a significant correlation (r = 0.55, p = 0.008) between adiponectin and ISGD. In conclusion, these data support: (1) the inability of basal glucose metabolism to accurately reflect hepatic insulin resistance, (2) the deleterious role of VAT in the development of insulin resistance in the liver, and (3) provide additional support for the positive influence of adiponectin against peripheral insulin resistance in obese, postmenopausal women.