Context: Excess abdominal adiposity is a primary factor for insulin resistance in older age.

Objective: To examine the role of abdominal obesity on adipose tissue, hepatic, and peripheral insulin resistance in aging and to examine impaired FFA metabolism as a mechanism in these relations.

Design: Cross-sectional study.

Setting: General Clinical Research Center.

Participants: Healthy, inactive older (>60 y) women (N=25) who were not on HRT or glucose-lowering medication. Women with abdominal circumference values above the median (>97.5 cm) were considered abdominally-obese.

Main Outcome Measures: Whole-body peripheral glucose utilization, adipose tissue lipolysis, and hepatic glucose production (HGP) measured using in vivo techniques according to a priori hypotheses.

Results: In the simple analysis, glucose utilization at the 40 mU insulin dose (6.3±2.8 vs. 9.1±3.4; p<0.05), the index of the insulin resistance of basal hepatic glucose production (IR_GP; 23.6±13.0 vs. 15.1±6.0; p<0.05), and insulin-stimulated suppression of lipolysis (35% vs. 54%; p<0.05) were significantly different between women with and without abdominal obesity, respectively. Using the Ra_glyc/FFA ratio as an index of fatty acid reesterification revealed markedly blunted reesterification in the women with abdominal adiposity under all conditions: basal (0.95±0.29 vs. 1.35±0.47; p<0.02); low- (2.58±2.76 vs. 6.95±5.56; p<0.02); and high-dose (4.46±3.70 vs. 12.22±7.13; p<0.01) hyperinsulinemia. Importantly, fatty acid reesterification was significantly (p<0.01) associated with abdominal circumference and hepatic and peripheral insulin resistance irrespective of total body fat.

Conclusion: These findings support the premise of disregulated fatty acid reesterification with abdominal obesity as a pathophysiological link to perturbed glucose metabolism across multiple tissues in aging.