Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies

Obesity is reaching epidemic proportions with recent worldwide figures estimated at 1.4 billion and rising year‐on‐year. Obesity affects all socioeconomic backgrounds and ethnicities and is a pre‐requisite for metabolic syndrome. Metabolic syndrome is a clustering of risk factors, such as central obesity, insulin resistance, dyslipidaemia and hypertension that together culminate in the increased risk of type 2 diabetes mellitus and cardiovascular disease. As these conditions are among the leading causes of deaths worldwide and metabolic syndrome increases the risk of type 2 diabetes mellitus fivefold and cardiovascular disease threefold, it is of critical importance that a precise definition is agreed upon by all interested parties. Also of particular interest is the relationship between metabolic syndrome and cancer. Metabolic syndrome has been associated with a plethora of cancers including breast, pancreatic, colon and liver cancer. Furthermore, each individual risk factor for metabolic syndrome has also an association with cancer. Our review collates internationally generated information on metabolic syndrome, its many definitions and its associations with life‐threatening conditions including type 2 diabetes mellitus, cardiovascular disease and cancer, providing a foundation for future advancements on this topic.     

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.     

Definition of the Metabolic Syndrome: What's New and What Predicts Risk?

The metabolic syndrome is a clustering of abnormalities that confers an increased risk of cardiovascular disease and type 2 diabetes. Five organizations have proposed definitions of the syndrome. Despite differences in specific criteria among the definitions, there is agreement that the major characteristics of the syndrome include central obesity (except in one definition), elevated blood pressure, dyslipidemia, and impaired glucose metabolism or insulin resistance. Large variations exist in the prevalence of the metabolic syndrome across countries and regions, ethnic groups, and gender. The prevalence is high and increasing, particularly in North and South American countries. The high prevalence, combined with the large number of people at risk for cardiovascular disease, type 2 diabetes, and other related disorders, suggests that the metabolic syndrome may present a major worldwide public health challenge in future.     

Metabolic and cardiovascular complications of highly active antiretroviral therapy for HIV infection

Highly active antiretroviral therapy (HAART) regimens, especially those including protease inhibitors have been shown to cause, in a high proportion of HIV-infected patients, a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease. A careful stratification of the cardiovascular risk of HIV-infected patients under HAART is needed according to the most recent clinical guidelines.     

The GH/IGF-1 Axis in Obesity: Physiological and Pathological Aspects

The cluster of cardiovascular risk factors-abdominal obesity, dyslipidaemia, insulin resistance and hypertension-has been recognized as the core of the metabolic syndrome. Adults with severe growth hormone (GH) deficiency have, to a large extent, features of the metabolic syndrome, and there is a strong inverse association between visceral fat accumulation and blunted GH secretion in adults. Hyposomatotropism in abdominal obesity has therefore been suggested to be of importance for its metabolic consequences. However, the underlying pathophysiological mechanisms are poorly understood. Prevalence of the metabolic syndrome is steadily increasing worldwide. Overnutrition and sedentary habits are the stigmata of modern society that predispose genetically susceptible individuals to develop central obesity and other features of the metabolic syndrome including glucose intolerance, hypertension and dyslipidemia. Although there are still no unified definitions of the syndrome, it is clear that this condition is associated with an increased risk for development of cardiovascular disease (CVD) and diabetes mellitus (DM). In this review, we discuss current evidence regarding alterations in the GH-IGF- 1 axis in abdominal obesity and its possible impact on other features of the metabolic syndrome.     

Association of syndromes of insulin resistance with coronary artery disease

Insulin resistance and its associated conditions, type 2 diabetes mellitus and the metabolic syndrome, have assumed great public health significance in relation to the development of atherosclerotic coronary artery disease. While the overall incidence of coronary artery disease has been declining, its incidence has been increasing in populations with insulin resistance. When insulin resistance is present in conjunction with type 2 diabetes mellitus and/or the metabolic syndrome, as well as other risk factors, the chance of developing coronary artery disease is strikingly increased as are the frequency and severity of its complications. In these situations, insulin resistance may behave synergistically with other risk factors. In addition to clustering with conventional risk factors, more recent evidence indicates that insulin resistance is linked with 'non-traditional' coronary artery disease risk factors and possibly with a pro-atherosclerotic inflammatory state.     

Cardiovascular risk in the metabolic syndrome: Fact or fiction?

In population-based studies, a cluster of cardiovascular risk factors comprising the metabolic syndrome (MetS) has been documented as predictive of cardiovascular disease events and type 2 diabetes. Currently, there are several proposed definitions of the MetS, although data support some advantages of using the 2005 National Cholesterol Education Program Adult Treatment Panel III definition, which is considered superior to most others, including the one from the 2005 International Diabetes Federation study. One controversial issue is that some of the conventional cardiovascular risk factors included in the MetS cluster appear to be equally predictive of cardiovascular outcomes as the syndrome itself (eg, the influence of smoking habits). Further observational and intervention studies are needed to explore this issue and target the core problem of the syndrome, which is proposed to be insulin resistance. Useful therapies for the metabolic syndrome include lifestyle modification and drugs that lower conventional cardiovascular risk factors, such as metformin, the "glitazones," and evidence-based drugs.     

Metabolic Syndrome in Andean Populations

The metabolic syndrome, a cluster of metabolic abnormalities, has been linked to both cardiovascular disease and type 2 diabetes mellitus risk. Several studies have shown that ethnicity is an important determinant for risk of developing the metabolic syndrome; therefore, further understanding of the prevalence and presentation of the metabolic syndrome in various ethnic groups is needed. Latin American communities, and particularly Andean countries, are largely understudied in relation to the metabolic syndrome and until recently, the prevalence of this metabolic disturbance in Andean Hispanics was unknown. Nonetheless, recent (and ongoing) population studies are providing important data regarding the prevalence and patterns of the metabolic syndrome in various Andean countries. This review aims to summarize and interpret the information provided by these studies in an effort to better characterize the metabolic syndrome in Andean Hispanics.     

Non-alcoholic fatty liver disease (NAFLD): why you should care, when you should worry, what you should do

For the diabetologist, non-alcoholic fatty liver disease (NAFLD) is important at both ends of its spectrum. It is an early warning sign of future risk of metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. It may also lead to late life-threatening sequela of diabetes mellitus in the event of progression to liver failure or hepatocellular carcinoma. This review will highlight the recent progress in understanding the natural history of non-alcoholic fatty liver disease and in developing a rational approach to its diagnosis, staging, and management. The pandemic prevalence of non-alcoholic fatty liver disease in Western countries necessitates both a high index of suspicion to identify cases and a non-invasive approach to staging, which is best achieved with clinical/biochemical panels and transient elastography. Lifestyle modification is the cornerstone of management. Recent clinical trials provide support for pharmacologic therapies directed at the metabolic syndrome and at protecting the liver but more data are needed. Bariatric surgery is appropriate for high-risk patients who fail conservative management. Patients with liver failure or hepatocellular carcinoma may be candidates for liver transplantation.     

Definition of the metabolic syndrome: current proposals and controversies

Metabolic syndrome includes a clustering of metabolic derangements that cause affected subjects to have an increased risk for developing diabetes, cardiovascular disease, and, according to recent epidemiologic studies, chronic kidney disease. The present review discusses four definitions of metabolic syndrome published by different national and international committees. In an effort to bridge the differences existent in those classifications, a unified definition that recognizes the increased biologic activity of the upper visceral fatty tissue and the strong association of abdominal obesity as a leading part of metabolic syndrome is proposed herein. The diagnosis of metabolic syndrome is reserved for pre-diabetic patients who share the risk of becoming diabetic or developing cardiovascular or chronic kidney disease.     

Alternative and Complementary Treatments for Metabolic Syndrome

Metabolic syndrome is defined by a cluster of cardiovascular disease risk factors that are associated with insulin resistance. In recent years, a number of innovative nutritional strategies have been proposed as safe alternative treatments to reduce the morbidity as well as the cost of treating metabolic syndrome. Of these, dietary supplementation with chromium picolinate or cinnamon extract has been studied most extensively. These interventions may attenuate insulin resistance and reduce the cardiovascular risk factors that together comprise the metabolic syndrome. However, more clinical trials are needed to determine the dose and duration of such treatments to make specific recommendations for populations with metabolic syndrome.     

Metabolic syndrome in African Americans: implications for preventing coronary heart disease

The metabolic syndrome represents a specific clustering of cardiovascular risk factors in the same individual (abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance, a prothrombotic state, and a proinflammatory state). Almost 50 million American adults (about one in four) have the metabolic syndrome, which puts them at increased risk for the development of diabetes mellitus and cardiovascular disease. African Americans, especially African-American women, have a high prevalence of the metabolic syndrome. This is attributable mainly to the disproportionate occurrence in African Americans of elevated blood pressure, obesity, and diabetes. Management of the metabolic syndrome consists primarily of modification or reversal of the root causes (overweight/obesity and physical inactivity) and therapy to reduce or control the risk factors. Although all components of the metabolic syndrome should be addressed, optimal control of atherogenic dyslipidemia and elevated blood pressure may reduce cardiovascular risk by more than 80%.     

Endothelial dysfunction and the metabolic syndrome

The metabolic syndrome is a highly prevalent multifaceted clinical entity produced through the interaction of genetic, hormonal, and lifestyle factors. A distinctive constellation of abnormalities precedes and predicts the accelerated development of atherogenesis and type 2 diabetes mellitus. Abnormalities of inflammation and coagulation represent emerging risk contributors associated with obesity and insulin resistance, central components of the metabolic syndrome, which act in concert with traditional abnormalities to increase cardiovascular risk. The initiation and progression of atherosclerosis may have its origins in impaired endothelial function that can be detected at the earliest stages of development of the syndrome. The basic elements of the metabolic syndrome and accelerated phase of atherogenesis are often silent partners that present many years before the onset of type 2 diabetes mellitus. The ability to detect and monitor subclinical vascular disease, as a reflection of the multiple factors that contribute to impair arterial wall integrity, holds potential to further refine cardiovascular risk stratification. Noninvasive assessment of vascular health may also aid the clinical decision-making process by guiding therapeutic interventions to optimize vascular protection in the metabolic syndrome.     

Cardiovascular risk associated with the metabolic syndrome

The term metabolic syndrome refers to a clustering of cardiovascular risk factors, most of which also share insulin resistance as an additional feature. Scientific effort has concentrated on understanding why these diverse cardiovascular risks co-occur in individuals and in determining the presumed common environmental or genetic factors that might underpin this. Clinically important developments include publication of standard definitions of the metabolic syndrome and recommendations for the use of type 2 diabetes and the presence of the metabolic syndrome as critical "risk stratifiers" in cardiovascular disease prevention. The remarkable recent secular increases in the prevalence of type 2 diabetes and obesity in many populations mean that the importance of the metabolic syndrome as a determinant of cardiovascular disease is likely to increase until these trends can be reversed.     

Das metabolisches Syndrom – ein umstrittenes diagnostisches Konzept

The metabolic syndrome is a heterogeneous complex that is clinically interpreted as an indicator of an increased risk of diabetes mellitus, cardiovascular morbidity and mortality. The diagnosis of metabolic syndrome is made, if at least three out of five factors - dysglycemia, visceral obesity, increased triglycerides, decreased HDL cholesterol, arterial hypertension - are present. Both the popularity and criticism of the metabolic syndrome have increased over recent years. One crucial problem are the currently existing definitions. This is illustrated on the basis of recent primary-care data from Germany, showing a prevalence ranging from 19% to 31% depending on the definition used. The debate about the rationale of the concept in terms of risk prediction for cardiovascular diseases points at one weakness of the concept. The entire discussion is mainly influenced by different approaches: a simple pedagogic approach, a pathophysiological approach, with insulin resistance as main focus of research, and a clinical-epidemiologic approach, where a cluster of different risk factors for cardiovascular disease risk prediction forms the initial scientific interests. Acknowledging these different perspectives might help reduce the confusion associated with the meaning and usefulness of the metabolic syndrome.     

Hypoglycemic pharmacological treatment of type 2 diabetes: Targeting the endothelium

Cardiovascular disease is by far the most common complication of type 2 diabetes and also the most serious one. Suffering from type 2 diabetes mellitus not only dramatically increases the risk of cardiovascular disease but is also associated with poor survival, both acutely and in the long term after a myocardial infarction. In fact, total mortality from coronary artery disease in subjects with type 2 diabetes mellitus, without a previous myocardial infarction, is as high as that of non-diabetic individuals with a previous infarction. Intense research efforts have thus been directed towards exploring the reasons for why particularly type 2 diabetic patients have such a poor prognosis suffering from cardiovascular disease. Obesity-related type 2 diabetes (“diabesity”), including the metabolic syndrome, is rapidly rising in prevalence. About 80% of all type 2 diabetes co-exists with insulin resistance. Endothelial dysfunction is a ubiquitous abnormality in insulin-resistant states that might contribute to premature atherosclerosis in a multifactorial and complex way. Low grade inflammation may play a role in development insulin resistance and type 2 diabetes and it has been proposed that atherosclerosis is basically an inflammatory disease. Thus, the pathophysiology of insulin resistance, the metabolic syndrome, and atherosclerosis may share inflammatory basis as a common denominator. Also, insulin resistance is not confined to skeletal muscle, adipose tissue and the liver, but also to the endothelium. Insulin resistance and endothelial dysfunction co-exist, where chronic inflammation may be a crucial factor. Accordingly, the possibility that physical activity or pharmacological agents that increase insulin sensitivity also improve endothelial function, or vice versa, has been investigated. Many different alterations in life style and drugs that improve endothelial function are known to lower the risk of contracting diabetes. In this review, the pharmacological treatment available against type 2 diabetes mellitus is discussed with particular emphasis on its impact on the endothelium.     

The metabolic syndrome: in need of a global mission statement

Aims The value of clinical definitions of the metabolic syndrome has been questioned, with confusion surrounding their intended use and purpose. Our aim was to construct a mission statement that outlines the value of the metabolic syndrome in clinical and public health settings. Methods Case studies have been used to demonstrate three key points. Results We argue here for recognition of obesity as being a crucial element within the metabolic syndrome but perhaps even more important before its development. We also contend that the concept does indeed have a role as a risk prediction tool, and that it could provide a useful metric for the scale and progress of the looming global epidemic of diabetes and cardiovascular disease. Conclusions Through appreciation of its purpose, and recognition of both its limitations and those attributes that make it unique and valuable, we believe we have demonstrated here that the metabolic syndrome deserves its place in the global toolbox of diabetes and CVD prevention.     

Clustering of silent cardiovascular risk factors in apparently healthy Hispanics

Ischaemic heart disease is one of the leading causes of cardiovascular morbidity and mortality. Because most factors leading to cardiovascular disease have a silent course, early screening is needed for prevention and for halting disease progression. In our centre, a programme was implemented in apparently healthy subjects for the early diagnosis and treatment of factors known to increment the risk of developing cardiovascular and metabolic disease. We present data from the first 153 individuals evaluated. The incidence of modifiable risk factors in our healthy population was as follows: overweight 33% (BMI: 25-30 kg/m(2)), obesity 45% (BMI >30 kg/m(2)), sedentarism 84%, arterial hypertension 15% (>140/90 mm Hg), hyperinsulinaemia 50%, glucose intolerance 14% (>160 mg/dl 120 min after 75 g glucose load), type 2 diabetes mellitus 5%, hypercholesterolaemia 50%, hypertriglyceridaemia 28%, and salt sensitivity 25%. Clustering of three or more cardiovascular risk factors was observed in 59% of the apparently healthy subjects. Obesity was associated with greater clustering of risk factors. The cardiovascular dysmetabolic syndrome was present in 72% of the obese individuals. These findings revealed a very high prevalence of cardiovascular risk factors in apparently healthy Hispanics. Even though these individuals were clinically asymptomatic, they are at increased risk for developing cardiovascular disease and type 2 diabetes mellitus. Mechanisms for the early detection and correction of modifiable risk factors in the healthy population must be implemented. Only through prevention will a reduction in the incidence of cardiovascular atherosclerotic disease and of type 2 diabetes mellitus be achieved.     

Eingeschr?nkte Fitness vs. Adipositas

The prevalence of metabolic syndrome and type?2 diabetes mellitus is increasing worldwide, resulting in premature cardiovascular mortality. This has been attributed to the increasing prevalence of obesity. However, multiple clinical and epidemiologic studies have also shown that high levels of cardiorespiratory fitness protect against the development of these metabolic disorders and at the same time reduce cardiovascular mortality. When comparing both parameters, cardiorespiratory fitness has been shown to be a more powerful parameter in the prevention of metabolic syndrome, type?2 diabetes, and cardiovascular disease than obesity. Thus, to prevent cardiovascular disease, it is mandatory to promote physical activity that will increase physical fitness. An English fulltext version of this article is available under Springerlink as supplemental material.     

Small for gestational age: short stature and beyond

Depending on the definitions used, up to 10% of all live-born neonates are small for gestational age (SGA). Although the vast majority of these children show catch-up growth by 2 yr of age, one in 10 does not. It is increasingly recognized that those who are born SGA are at risk of developing metabolic disease later in life. Reduced fetal growth has been shown to be associated with an increased risk of insulin resistance, obesity, cardiovascular disease, and type 2 diabetes mellitus. The majority of pathology is seen in adults who show spontaneous catch-up growth as children. There is evidence to suggest that some of the metabolic consequences of intrauterine growth retardation in children born SGA can be mitigated by ensuring early appropriate catch-up growth, while avoiding excessive weight gain. Implicitly, this argument questions current infant formula feeding practices. The risk is less clear for individuals who do not show catch-up growth and who are treated with GH for short stature. Recent data, however, suggest that long-term treatment with GH does not increase the risk of type 2 diabetes mellitus and the metabolic syndrome in young adults born SGA.