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      Metabolic Vascular Syndrome: New Insights into a Multidimensional Network of Risk Factors and Diseases

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          Abstract

          Background: Since 1981, we have used the term metabolic syndrome to describe an association of a dysregulation in lipid metabolism (high triglycerides, low high-density lipoprotein cholesterol, disturbed glucose homeostasis (enhanced fasting and/or prandial glucose), gout, and hypertension), with android obesity being based on a common soil (overnutrition, reduced physical activity, sociocultural factors, and genetic predisposition). We hypothesized that main traits of the syndrome occur early and are tightly connected with hyperinsulinemia/insulin resistance, procoagulation, and cardiovascular diseases. Methods: To establish a close link between the traits of the metabolic vascular syndrome, we focused our literature search on recent original work and comprehensive reviews dealing with the topics metabolic syndrome, visceral obesity, fatty liver, fat tissue inflammation, insulin resistance, atherogenic dyslipidemia, arterial hypertension, and type 2 diabetes mellitus. Results: Recent research supports the concept that the metabolic vascular syndrome is a multidimensional and interactive network of risk factors and diseases based on individual genetic susceptibility and epigenetic changes where metabolic dysregulation/metabolic inflexibility in different organs and vascular dysfunction are early interconnected. Conclusion: The metabolic vascular syndrome is not only a risk factor constellation but rather a life-long abnormality of a closely connected interactive cluster of developing diseases which escalate each other and should continuously attract the attention of every clinician.

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          Most cited references39

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          Selective versus total insulin resistance: a pathogenic paradox.

          Mice with type 2 diabetes manifest selective hepatic insulin resistance: insulin fails to suppress gluconeogenesis but continues to activate lipogenesis, producing the deadly combination of hyperglycemia and hypertriglyceridemia. In this issue of Cell Metabolism, Biddinger et al. (2008) show that mice with total hepatic insulin resistance exhibit hyperglycemia without hypertriglyceridemia-a state paradoxically less severe than selective insulin resistance.
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            The distinction of metabolically 'healthy' from 'unhealthy' obese individuals.

            The prevalence and severity of obesity are dramatically increasing throughout the world. Obesity causes a decline in life expectancy due to its associated metabolic and cardiovascular comorbid disorders. Therefore, it will become more important to distinguish obese individuals at high risk for obesity-related metabolic diseases from those who are metabolically 'healthy'. This review focuses on recent evidence suggesting that normal adipose tissue function contributes to the healthy obese phenotype. The majority of individuals with obesity develop insulin resistance, type 2 diabetes, dyslipidemia, gout, hypertension and cardiovascular disease. However, approximately 10-25% of obese individuals are metabolically healthy most likely due to preserved insulin sensitivity. Recent studies suggest that inflammation of visceral adipose tissue, ectopic fat deposition and adipose tissue dysfunction mediate insulin resistance in human obesity independently of total body fat mass. This suggests that mechanisms beyond a positive caloric balance such as inflammation and adipokine release determine the pathological metabolic consequences in patients with obesity. Recommendations for obesity treatment should distinguish the metabolically 'healthy' from 'unhealthy' obese phenotype to identify early the obese person who will benefit the most from losing weight. In addition, novel antiobesity treatment strategies targeting adipose tissue dysfunction are needed.
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              Are there persons who are obese, but metabolically healthy?

              The aim of this article was to review the evidence for a metabolically normal subset of the obese and its implications for clinical and research work. The methods included literature review and correspondence with authors. Since 1947, when Vague described a relation between distribution of body fat and the risk factors for cardiovascular disease, much evidence has suggested that early onset of the obesity, hyperplasia of normal adipocytes, and normal quantities of visceral abdominal fat may be associated with a favorable metabolic response in obese subjects. Analyses in 1973 by Keyes and later by Reuben Andres in 1980 suggested that obesity for some was not a risk factor and might even be an asset. Recently, in the study by Bonora et al of the relation between insulin resistance and the 4 main disorders of the metabolic syndrome in the Bruneck epidemiologic study, a subgroup of obese individuals with a normal metabolic response was evident. In a current study by Brochu et al of an obese metabolically normal subgroup of postmenopausal women, visceral abdominal fat estimated by computed tomography (CT) scan and age of onset were significant variables. The obese, metabolically normal subgroup (OBMN) must be taken into consideration in both clinical and research work. Persons with OBMN and their parents may be wrongly blamed because of the obesity. Attempts at weight loss may be counterproductive. The criteria for selection of obese research subjects may favor inclusion of an OBMN subset, which may invalidate statistical analysis. Findings suggesting the OBMN subset include family members with uncomplicated obesity, early onset of the obesity, fasting plasma insulin within normal range, and normal distribution of the excess fat. Hormonal, genetic studies, and prospective studies will help to clarify the significance and underlying mechanisms of this subset. Copyright 2001 by W.B. Saunders Company
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                Author and article information

                Journal
                VIS
                VIS
                10.1159/issn.2297-4725
                Visceral Medicine
                Visc Med
                S. Karger GmbH (Freiburg, Germany karger@ 123456karger.de http://www.karger.de )
                978-3-318-05813-0
                978-3-318-05814-7
                2297-4725
                2297-475X
                October 2016
                07 October 2016
                : 32
                : 5
                : 319-326
                Affiliations
                aDepartment of Endocrinology, Diabetology, Cardiology and General Medicine, St. Elisabeth-Krankenhaus Leipzig, Leipzig, Germany; bLeipziger Institut für Präventivmedizin GmbH, Leipzig, Germany; cGWT-TUD GmbH, Dresden Technical University, Dresden, Germany; dMedical Clinic III, University Hospital Carl Gustav Carus, Dresden, Dresden, Germany
                Article
                450866 PMC5122997 Visc Med 2016;32:319-326
                10.1159/000450866
                PMC5122997
                27921043
                c0a8f824-b287-4d86-a13f-1b25c5dd62f9
                © 2016 S. Karger GmbH, Freiburg

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                History
                Page count
                Figures: 4, References: 59, Pages: 8
                Categories
                Review Article

                Medicine,General social science
                Common soil,Type 2 diabetes,Insulin resistance,Obesity,Metabolic vascular syndrome,Metabolic syndrome

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