Reducing visceral adipose tissue mass is essential for improving endothelial function in type 2 diabetes prone individuals

Objective: In obesity, particularly increased visceral-(VAT), but not total (TAT) adipose tissue mass is a major source of proinflammatory cytokine expression and secretion. VAT, more than TAT, is associated with endothelial dysfunction (ED), which is an accepted risk factor for atherosclerosis. Consequently, we hypothesized that during a lifestyle intervention specifically a decrease in VAT, rather than TAT, is associated with improved ED and vascular adhesion molecules in type 2 diabetes prone subjects. Methods: Analyses were done in 189 individuals (age: 45.4 +/- 0.8 years) at increased risk of type 2 diabetes, who underwent a 9-month lifestyle intervention. ED expressed as flow mediated dilation (FMD) of the brachial artery, sE-selectin, sV-CAM, sI-CAM, TAT and VAT (measured by magnetic resonance tomography) was determined. Results: There was a mean decrease in body weight (-3%, p < 0.0001), TAT (-7.6%, p < 0.0001) and VAT (-12.5%, p < 0.0001), while FMD increased (+ 9.1%, p = 0.04). The change in FMD was not associated with change in body weight (p = 0.35) or TAT (p = 0.21) but with a decrease in VAT (r = -0.19, p = 0.009). In a post hoc analysis, the subjects were divided by the median change in VAT into responders and non-responders. FMD increased only in the responders (from 6.2 +/- 0.4% to 8.0 +/- 0.5%, p = 0.0005) but not in the non-responders (p = 0.15). Also sE-selectin significantly decreased only in the responders (from 54 +/- 4 ng/ml to 47 +/- 3 ng/ml; p = 0.03). Conclusion: During a lifestyle intervention, not weight loss or decrease in TAT, but decrease in VAT is associated with improved ED in individuals prone to type 2 diabetes. Therefore, primary cardiovascular prevention should focus specifically on reducing VAT rather than body weight alone. (C) 2010 Elsevier Ireland Ltd. All rights reserved.