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