Elsevier

Atherosclerosis

Volume 212, Issue 2, October 2010, Pages 575-579
Atherosclerosis

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

https://doi.org/10.1016/j.atherosclerosis.2010.06.042Get rights and content

Abstract

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.

Introduction

Atherosclerosis develops early in life, leading to new views of what is currently considered as “primary prevention” of cardiovascular disease. There is no doubt about the deleterious effects of traditional risk factors during adolescence and adulthood on the vascular system, however, there is some evidence that also non-traditional risk factors should be taken into account, already in the first decade of life [1]. Recent research in the past years has identified increased visceral adipose tissue (VAT) mass and ectopic fat deposited in the liver, to be potent mediators of systemic inflammation and subsequently, negatively influencing endothelial dysfunction [2], [3], [4], [5], [6]. Endothelial dysfunction in turn has been proven to be predictive for cardiovascular complications [7], [8], [9], [10]. Intervention studies have demonstrated that exercise-focused lifestyle changes are capable of reducing body weight and subclinical inflammation and being effective regarding the reduction of cardiovascular events [11], [12], [13]. This is accompanied by improvement in flow mediated dilation (FMD) of the large arteries [14], [15], [16], [17]. We have recently shown that serum levels of MCP-1, a modulator of monocyte function, which in large part is secreted from VAT, have no effect on endothelium-dependent NO-induced vasodilation [18]. Therefore, given the cross-sectional association between visceral adiposity and impaired vascular function, we hypothesized that a reduction in VAT-mass is essential for effective primary cardiovascular prevention, estimated by changes in FMD and endothelial markers during lifestyle intervention in 189 middle-aged subjects, who are at increased risk to develop type 2 diabetes.

Section snippets

Methods and procedures

This analysis included a total of 189 subjects (120 women and 69 men, mean age 45.4 ± 0.8 [SEM] years) without diabetes and clinical evidence for cardiovascular disease, who participated in the ongoing Tübingen Lifestyle Intervention Program (TULIP). This study was designed to find parameters that predict the effect of a lifestyle intervention with diet and moderate increase in aerobic physical activity to improve prediabetes phenotypes and the cardiovascular risk profile [19], [20]. The

Baseline parameters between groups

Anthropometrical data, laboratory findings and vascular parameters of the study population at baseline and follow up are shown in Table 1, Table 2. These parameters covered a wide range, allowing to carefully studying relationships between them.

The responder and the non-responder groups did not differ in age or gender distribution. At baseline there was also no significant difference in the classical cardiovascular risk profile between the groups. Blood pressure and smoking habits e.g. were

Discussion

In the present study we found that the decrease in VAT, but not TAT, during lifestyle intervention was accompanied by improvement in vascular function in a population at increased risk to develop type 2 diabetes. The decrease in VAT was accompanied by amelioration of a number of risk factors potentially influencing vascular parameters. To test for the impact of these other parameters that improved only in the responder group, we dichotomised the study population according to the median change

Conflict of interest

The authors have no conflicts of interest to declare.

Acknowledgments

This study was supported by a research grant from the German Research Foundation (Deutsche Forschungsgemeinschaft DFG-KFO 114). NS is supported by a Heisenberg-Grant from the DFG (STE 1096/1-1). This study was supported in part by a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V.).

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