Metabolic syndrome, diabetes and cardiovascular events: current controversies and recommendations

Metabolic syndrome is now present in up to 40% of the United States adult population and is associated with a nearly a two fold increase in cardiovascular events, independent of the presence of diabetes mellitus. The concept of the metabolic syndrome as clinical syndrome has recently been challenged, however, and controversy exists as to whether the metabolic syndrome adds to cardiovascular risk above and beyond the sum of its independent metabolic components. Given the epidemic of obesity in both industrialized and third world countries, this issue is of great importance. The current article puts this controversy into perspective and explores the association of metabolic syndrome with both accelerated cardiovascular risk and the risk of development of type 2 diabetes. The pathophysiology of the increased risk of cardiovascular disease in diabetes associated with metabolic syndrome is discussed and the importance of early recognition of metabolic syndrome and potential role of addressing insulin resistance is stressed. Clearly more data is needed, but it is safe to say that metabolic syndrome is a worldwide epidemic in association with central obesity and underlying insulin resistance, which will propel a marked increase in cardiovascular events and diabetes mellitus in the years to come. Further research is needed to understand the role of more aggressive therapy in preventing type 2 diabetes and cardiovascular events in the population.     

Metabolic syndrome and NASH

Clinical and epidemiologic studies have associated non-alcoholic fatty liver with the metabolic syndrome, with insulin resistance as the pivotal pathogenic factor. Obesity, type 2 diabetes mellitus, dyslipidemia, and hypertension contribute to risk for liver disease and to disease progression. The presence of multiple metabolic abnormalities is associated with the severity of liver disease. Patients have a high risk for cardiovascular morbidity and mortality, mediated by early atherosclerosis. This evidence has precise therapeutic implications: only a behavioral approach to lifestyle correction will address all alterations characterizing the metabolic syndrome, including metabolic liver disease.     

代谢综合征的临床处理策略

代谢综合征是一组代谢起源的、相互关联的、群集发生的危险因子。它们直接促进粥样硬化性心血管疾病和2型糖尿病的发生、发展。其首要处理目标是降低临床动脉粥样硬化疾病的风险。一线治疗应针对动脉粥样硬化疾病主要危险因子:吸烟、高低密度脂蛋白胆固醇(LDL-C)水平、高血压和糖尿病。其另一处理目标是预防2型糖尿病的发生。其处置重点应是通过生活方式的改变减轻可纠正的内在危险因子(肥胖、缺乏体力活动和致粥样硬化饮食)。     

Metabolic Syndrome,Androgens, and Hypertension

Obesity is one of the constellation of factors that make up the definition of the metabolic syndrome. Metabolic syndrome is also associated with insulin resistance, dyslipidemia, hypertriglyceridemia, and type 2 diabetes mellitus. The presence of obesity and metabolic syndrome in men and women is also associated with increased risk of cardiovascular disease and hypertension. In men, obesity and metabolic syndrome are associated with reductions in testosterone levels. In women, obesity and metabolic syndrome are associated with increases in androgen levels. In men, reductions in androgen levels are associated with inflammation, and androgen supplements reduce inflammation. In women, increases in androgens are associated with increases in inflammatory cytokines, and reducing androgens reduces inflammation. This review discusses the possibility that the effects of androgens on metabolic syndrome and its sequelae may differ between males and females.     

Identification and treatment of metabolic complications in pediatric obesity

Metabolic consequences of obesity including insulin resistance, type 2 diabetes mellitus, hyperlipidemia, hypertension, polycystic ovarian syndrome, and non-alcoholic fatty liver infiltration are rapidly emerging in the pediatric population. Identifying effective strategies for identifying and treating these obesity related co-morbidities in children are crucial to the prevention of future cardiovascular disease and poor health outcomes. This review discusses the pathophysiologic connections between obesity, metabolic disease and cardiovascular risk. Current evidence and recommendations for screening and treatment for the metabolic consequences of pediatric obesity are reviewed.     

Metabolic syndrome as a predictor of type 2 diabetes,and its clinical interpretations and usefulness

Metabolic syndrome is defined as a cluster of glucose intolerance, hypertension, dyslipidemia and central obesity with insulin resistance as the source of pathogenesis. Although several different combinations of criteria have been used to define metabolic syndrome, a recently published consensus recommends the use of ethnic‐specific criteria, including waist circumference as an indicator of central obesity, triglyceride and high‐density lipoprotein (HDL) cholesterol as indicators of dyslipidemia, and blood pressure greater than 130/85 mmHg. The definition of dysglycemia, and whether central obesity and insulin resistance are essential components remain controversial. Regardless of the definition, the prevalence of metabolic syndrome is increasing in Western and Asian countries, particularly in developing areas undergoing rapid socioenvironmental changes. Numerous clinical trials have shown that metabolic syndrome is an important risk factor for cardiovascular disease (CVD), type 2 diabetes mellitus and all‐cause mortality. Therefore, metabolic syndrome might be useful as a practical tool to predict these two major metabolic disorders. Comprehensive management of risk factors is very important to the improvement of personal and public health. However, recent studies have focused on the role metabolic syndrome plays as a risk factor for CVD; its importance in the prediction of incident diabetes is frequently overlooked. In the present review, we summarize the known evidence supporting metabolic syndrome as a predictor for type 2 diabetes mellitus and CVD. Additionally, we suggest how metabolic syndrome might be useful in clinical practice, especially for the prediction of diabetes.     

Prevalence of diabetes mellitus, hyperinsulinaemia and metabolic syndrome among 755 adult patients with HIV-1 infection

Metabolic complications of antiretroviral therapy in HIV-infected patients include insulin resistance, diabetes mellitus, dyslipidaemia and lipodystrophy syndrome. Metabolic syndrome is an aggregation of central obesity with glucose and lipid metabolism alterations that confers an increased risk of cardiovascular disease, which reproduces the antiretroviral-associated metabolic and morphological abnormalities. In this study, we report the prevalence of diabetes mellitus, hyperinsulinaemia and metabolic syndrome among 755 adult patients with HIV-1 infection referred to our outpatients unit. The prevalence of diabetes mellitus and metabolic syndrome was 4.5% and 9.1%, respectively. A longer exposure to antiretroviral therapy and a diagnosis of lipodystrophy syndrome were significantly associated with both metabolic disturbances.     

Is the metabolic syndrome a real clinical entity and should it receive drug treatment?

Metabolic syndrome represents a cluster of risk factors commonly associated with obesity and diabetes that in turn are associated with an increased risk of cardiovascular disease. The worldwide prevalence of metabolic syndrome, obesity, and diabetes is on the rise, leading to serious public health concerns surrounding the downstream consequences in the form of premature cardiovascular disease. In this review, we examine the debate surrounding the characterization and diagnosis of metabolic syndrome and discuss potential treatment options.     

代谢综合征与病毒性肝炎的研究进展

代谢综合征是一组以胰岛素抵抗（IR）作为共同病理因素的相关临床症候群,可导致2型糖尿病、非酒精性脂肪性肝病、心血管疾病等。部分研究显示,代谢综合征是加重慢性病毒性肝炎患者肝组织损伤的危险因素,但相关结论存在争议,且具体作用机制未完全阐明。本文就目前代谢综合征与病毒性肝炎的研究进展作一综述。     

代谢综合征与冠心病

代谢综合征已成为新世纪,继高血压、糖尿病、肥胖和血脂异常等疾病之后的又一慢性流行性疾病。代谢综合征的成分如肥胖、2型糖尿病、致粥样硬化血脂表型与高血压是冠心病重要的独立危险因素,每一个成分都可直接促进动脉粥样硬化发生。由于代谢综合征是这些独立危险因素的聚集,因此代谢综合征伴有更大比例、更大程度和病变更广泛的冠心病发病率及病死率。但代谢综合征所有组分对心血管危险的确切影响还需进行更深入的研究,今后代谢综合征的研究和防治还需多个学科和专业人才的合理整合。     

Adiposity, type 2 diabetes and the metabolic syndrome in breast cancer

Upper body obesity and the related metabolic disorder type 2 diabetes have been identified as risk factors for breast cancer, and associated with late-stage disease and a poor prognosis. Components of the metabolic syndrome, including visceral adiposity, insulin resistance, hyperglycemia and hyperinsulinemia, with or without clinically manifest diabetes mellitus, low serum high-density lipoprotein cholesterol and hypertension have all been related to increased breast cancer risk. The biochemical mechanisms include extraglandular oestrogen production, reduced sex hormone-binding globulin with consequent elevation of the bioactive plasma free oestradiol and increased insulin biosynthesis, all of which exert mitogenic effects on both untransformed and neoplastic breast epithelial cells. Obesity, type 2 diabetes and the metabolic syndrome also have in common an increased production of leptin and a decreased production of adiponectin by adipose tissue, with consequent elevations and reductions, respectively, in the circulating levels of these two adipokines. These changes in plasma leptin and adiponectin, acting through endocrine and paracrine mechanisms, have been associated in several studies with an increase in breast cancer risk and, perhaps, to more aggressive tumours; studies in vitro showed that leptin stimulates, and adiponectin inhibits, tumour cell proliferation and the microvessel angiogenesis which is essential for breast cancer development and progression.     

Impact of obesity on cardiovascular disease

The epidemiology of cardiovacular disease risk factors is changing rapidly with the obesity pandemic. Obesity is independently associated with the risks for coronary heart disease, atrial fibrillation, and heart failure. Intra-abdominal obesity is also unique as a cardiovascular risk state in that it contributes to or directly causes most other modifiable risk factors, namely, hypertension, dysmetabolic syndrome, and type 2 diabetes mellitus. Obesity can also exacerbate cardiovascular disease through a variety of mechanisms including systemic inflammation, hypercoagulability, and activation of the sympathetic and renin-angiotensin systems. Thus, weight reduction is a key strategy for simultaneous improvement in global cardiovascular risk, with anticipated improvements in survival and quality of life.     

Metabolic syndrome: an evolving threat in the genesis of coronary artery disease

Cardiovascular disease is an escalating worldwide health problem. Effective tools to predict and prevent its development and progression are needed. Correctly diagnosing the metabolic syndrome, which identifies people at higher risk for developing diabetes mellitus and cardiovascular disease, may be valuable in guiding treatment and prevention of these major disorders. Several important definitions of the metabolic syndrome have been proposed. The authors discuss these definitions and how they vary in terms of their relationship to incident cardiovascular disease, type 2 diabetes mellitus, and surrogate markers of atherosclerosis. Establishing clarity on what is meant by the metabolic syndrome and agreement as to its underlying basis is needed to reach consensus between the many different definitions that have been proposed. This is particularly the case if it is to become a useful adjunct in clinical practice to identify those who may benefit from more intensive lifestyle interventions and more detailed short-term risk assessments.     

Ocular associations of metabolic syndrome

Metabolic syndrome is a cluster of diseases including central obesity, dyslipidemia, hyperglycemia, and high blood pressure. People with metabolic syndrome have been shown to be at an increased risk of developing cardiovascular disease, beyond the risk associated with individual components of the syndrome. The association of diabetes and hypertension with retinopathy, cataract, and raised intraocular pressure is well known. This review highlights the association of metabolic syndrome, including all its components, with various ocular conditions such as retinopathy, central retinal artery occlusion, cataracts, and raised intraocular pressure.     

Carotid Intima-Media Thickness and Brachial Artery Flow-Mediated Dilatation in Patients with and without Metabolic Syndrome

BACKGROUND, Metabolic syndrome has recently emerged as a marker of future cardiovascular risk. However its incremental value for this purpose, over conventional cardiovascular risk factors and diabetes mellitus in particular, is debated. The present study was conducted to determine the extent of subclinical atherosclerosis in patients with metabolic syndrome, and compare it with the same in individuals with cardiovascular risk factors not having metabolic syndrome. METHODS, A total of 156 individuals seeking outpatient cardiac consultation for various indications were included in the study and were divided into four groups - group 1: cardiovascular risk factors present but not metabolic syndrome (n = 60) : group 2 : metabolic syndrome without diabetes mellitus or coronary artery disease (n = 21) ;group 3: metabolic syndrome with diabetes mellitus without coronary artery disease ( n = 27) ;and group 4:patients with documented coronary artery disease (n = 48). Metabolic syndrome was diagnosed on the basis of Adult Treatment Panel III (ATPIII) criteria. All patients underwent assessment of carotid intima-media thickness and brachial artery flow-mediated vasodilatation. RESULTS, Both carotid intima-media thickness and brachial artery flow-mediated vasodilatation were similar in groups 1 and 2 (carotid intima-media thickness: 0.687 -/+ 0.13mm and 0.706 -/+0.23mm, p = 0.963; brachial artery flow-mediated vasodilatation: 11.80 -/+ 5.16% and 12.87 -/+ 7.04%, respectively, p =0.883) , but group 3 patients had significantly higher carotid intima-media thickness (0.774 +/- 0.15mm, p = 0.047) and significantly lower brachial artery flow-mediated vasodilatation (7.37 -/+ 6.12%, p -/+ 0.007) as compared to group 1 patients. There was no significant difference in the two parameters between groups 3 and 4 (carotid intima-media thickness in group 4:0.789 -/+ 0.16mm,p = 0.976 and brachial artery flow-mediated vasodilatation:5.86 -/+ 3.85%, p -/+ 0.709). CONCLUSIONS, In absence of diabetes mellitus, metabolic syndrome was not associated with greater extent of subclinical atherosclerosis compared to individual cardiovascular risk factors. Presence of diabetes mellitus, however, resulted in significant endothelial dysfunction and evidence of subclinical atherosclerosis, similar to that seen in patients with already established coronary artery disease.     

Nutraceuticals in Diabetes and Metabolic Syndrome

Metabolic syndrome represents a clustering of risk factors related to an elevated risk of cardiovascular disease and type 2 diabetes. Occurrence of both metabolic syndrome and diabetes and their vascular complications share several pathogenetic features including subclinical, low‐grade inflammation, altered oxidative/antioxidant status, and persistent platelet activation. Despite the availability of multiple interventions to counteract these metabolic changes, including appropriate diet, regular exercise, weight control and drugs, epidemiological data are witnessing the growing trend of the problem, reflecting both the multifactorial nature of these diseases as well as the scarce compliance of patients to established strategies. Several nutraceuticals used in clinical practice have been shown to target the pathogenesis of diabetes mellitus, metabolic syndrome and their complications and to favorably modulate a number of biochemical and clinical endpoints. These compounds include antioxidant vitamins, such as vitamins C and E, flavonoids, vitamin D, conjugated linoleic acid, omega‐3 fatty acids, minerals such as chromium and magnesium, α‐lipoic acid, phytoestrogens, and dietary fibers. Several areas of concern exist regarding the use of dietary supplements and nutraceuticals in this setting, including product standardization, definition of optimal dosing regimen, potential side effects, drug interactions, and need for evidence‐based indications.     

The 2009 Stock Conference Report: Inflammation,Obesity and Metabolic Disease

Obesity is linked with many deleterious health consequences and is associated with increased risk of chronic disease including type 2 diabetes, atherosclerosis and certain forms of cancer. Recent work has highlighted the impact of obesity to activate inflammatory gene networks and suggests a causal function of inflammation in the pathogenesis of the metabolic syndrome. Since 2005, when Dr Gokhan Hotamisligil chaired the fourth Stock Conference in Istanbul, Turkey, entitled ‘Obesity and Inflammation’, there has been an explosion of studies investigating the relationship between obesity, inflammation and substrate metabolism. The exuberance surrounding this field of research is exemplified by the body of work that has been published in these past 4 years, including over 1400 publications. During this time, several novel mechanisms relating to cellular inflammation have been uncovered including the role of the hematopoietic system, toll‐like receptor activation, endoplasmic reticulum stress and very recently T‐cell activation in obesity‐induced insulin resistance. These discoveries have led us to rethink cellular nutrient sensing and its role in inflammation and metabolic disease. Despite burgeoning investigation in this field, there still remain a number of unanswered questions. This review that evolved from the 2009 Stock Conference summarizes current research and identifies the deficiencies in our understanding of this topic. The overall goal of this Stock Conference was to bring together leading investigators in the field of inflammation and obesity research in the hope of fostering new ideas, thus advancing the pursuit of novel therapeutic strategies to reduce disease risk and or better treat chronic disease including type 2 diabetes, cardiovascular disease and cancer.     

加强代谢综合征与慢性肝病关系的研究

当前代谢综合征正呈全球化的流行趋势,并已成为我国慢性肝病愈来愈重要的病因或诱因.最近大量研究表明,代谢综合征不但是非酒精性脂肪性肝病发生发展的重要危险因素,还与酒精性肝病、慢性乙型肝炎、慢性丙型肝炎以及隐源性肝病患者肝硬化和肝癌的高发密切相关.此外,合并代谢综合征的慢性肝病患者发生2型糖尿病和动脉粥样硬化性心血管疾病的危险性显著增加.提示肝病医生需加强代谢综合征与肝病的关系及其诊疗对策的临床研究.     

Guidelines Updates in the Treatment of Obesity or Metabolic Syndrome and Hypertension

Obesity and overweight are nowadays very prevalent worldwide. They are known to be linked with an increased risk of developing cardiovascular comorbidities and mortality. Abdominal obesity is frequently associated with a collection of metabolic disorders that include elevated blood pressure, characteristic lipid abnormalities (low high-density lipoprotein cholesterol and high triglycerides) and increased fasting glucose, with an underlying situation of insulin resistance, which has been defined as metabolic syndrome, conferring a high cardiovascular risk profile to these subjects. A multidisciplinary approach is required, including lifestyle changes and pharmacological and surgical approaches. Intensive management of all the risk factors of the metabolic syndrome is also needed to reduce body weight and waist circumference, lessen insulin resistance and avoid the development of new-onset diabetes and cardiovascular disease associated with this entity. This article will review the recently published literature and guideline updates on this topic, although it is not yet included in the highlights.     

Epidemiology of the diabetic heart

Diabetes mellitus is a worldwide epidemic. Cardiovascular disease remains the major cause of morbidity and mortality in people with diabetes. Studies have suggested that increased risk of cardiovascular disease is not restricted to type II or type I diabetes mellitus, but extends to prediabetic stages such as impaired fasting glucose, impaired glucose tolerance, metabolic syndrome, and obesity. Insulin resistance, impaired fasting glucose, impaired glucose tolerance, and diabetes mellitus form a continuous sequence of risk for cardiovascular disease. Therefore, cardiovascular disease mortality and morbidity within the diabetes epidemic grow into vast proportions. Evidence also exists that diabetic patients have a high prevalence of heart failure or impaired diastolic and systolic cardiac function subsequent to the combination of coronary artery disease, hypertension, and diabetic cardiomyopathy. In view of the proportions of this new epidemic, prevention of diabetes and its prediabetic states is likely to be the most effective strategy to prevent serious cardiovascular events.