Context: It is unclear whether adipocyte size or body fat distribution is most strongly linked to the metabolic complications of obesity.

Objective: Our objective was to test whether adipocyte size better predicts metabolic characteristics of obesity than body composition.

Design, Participants, and Setting: We analyzed the relationship between metabolic and anthropometric data collected from 432 largely Caucasian research volunteers (264 women) participating in studies conducted in the Mayo General Clinical Research Center between 1995 and 2008.

Main Outcome Measures: Metabolic variables included fasting plasma glucose, insulin, and triglyceride concentrations. Anthropometric variables included body composition, fat distribution, and sc abdominal and femoral adipocyte size.

Results: Using both univariate and multivariate regression analysis, fasting triglyceride in both men and women was best predicted by computed tomography of visceral fat area. Fasting insulin concentrations were best predicted by sc abdominal fat area in women (r² = 0.40; P < 0.01) and body mass index in men (r² = 0.53; P < 0.0001); adipocyte size did not contribute independently. In men, fasting glucose concentrations were predicted by femoral adipocyte size (partial r² = 0.07; P = 0.002), body mass index (partial r² = 0.03; P = 0.07), and age (partial r² = 0.02; P = 0.06). In women, fasting glucose was predicted by abdominal sc fat area (partial r² = 0.12; P < 0.0001) and age (partial r² = 0.03; P = 0.01).

Conclusions: Our hypothesis that adipocyte size is the best predictor of metabolic characteristics was not supported in this population. The alternative explanation is that fat mass and body fat distribution have more influence on metabolic responses than adipocyte size.