The metabolic syndrome

This article provides an overview of the metabolic syndrome, a collection of cardiovascular risk factors that denote a high-risk, multifactorial,adverse cardiovascular state, which is largely the result of obesity and resulting insulin resistance. Treatment for the metabolic syndrome should be focused primarily on modifying lifestyle,with reduction of the underlying obesity and insulin resistance. A combination of chemoprevention and lifestyle modification may prevent many if not most cases of diabetes if treatment is instituted early.     

The significance of lifestyle as a risk factor for the metabolic syndrome

The metabolic syndrome is featured by obesity, dyslipidemia and insulin resistance, additionally associated with inflammatory and fibrinolytic dysfunctions, all of which are risk factors of cardiovascular diseases and type 2 diabetes. The lifestyle factors that could cause and aggravate the metabolic syndrome are physical inactivity, calorie-dense diet, habitual alcohol drinking and smoking, and psychosocial stress. Energy excess along with a lot of saturated fat, i.e. more fast food and sugar-containing drinks, and sedentary lifestyle like television viewing are contributing to the epidemic of obesity. The significance of lifestyle from birth to adulthood will be reviewed in the context of the metabolic syndrome, as well as the background and environment in which the convenient lifestyle spread far and wide among us.     

Metabolic syndrome and risk of stroke

Stroke is one of the leading causes of death in the United States and worldwide. Metabolic syndrome, comprising abdominal obesity, elevated triglyceride levels, low levels of high-density lipoprotein cholesterol, elevated blood pressure, and impaired glucose metabolism, greatly increases the risk of cardiovascular disease, including stroke. The high prevalence of metabolic syndrome among individuals who experience stroke makes the metabolic syndrome a target for aggressive intervention and therapy. In addition to lifestyle changes, therapy with statins, angiotensin-converting enzyme inhibitors, insulin sensitizers, and antithrombotic agents to aggressively treat elements of metabolic syndrome is warranted. Statins favorably affect both lipid and nonlipid risk factors for stroke, making them a useful tool for stroke prevention.     

A practical "ABCDE" approach to the metabolic syndrome

The metabolic syndrome comprises a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus that are due to abdominal obesity and insulin resistance. This increasingly important proinflammatory condition remains both underrecognized and undertreated. To aid physicians in their approach to the metabolic syndrome, we assessed and synthesized the literature on cardiovascular risk assessment and early intervention for risk reduction. We performed a comprehensive search of MEDLINE and the Cochrane database for peer-reviewed clinical studies published from January 1, 1988, to December 31, 2007, augmented by consultation with content experts. We used the search terms metabolic syndrome, abdominal obesity, waist circumference, insulin resistance, cardiovascular disease, prediabetes, diabetes, treatment, prevention, aspirin, hypertension, cholesterol, atherogenic dyslipidemia, lifestyle therapy, diet, and exercise. Criteria used for study review were controlled study design, English language, relevance to clinicians, and validity based on experimental design and appropriateness of conclusions. Although growing evidence supports early intervention in patients with the metabolic syndrome, many physicians do not recognize the risk associated with this condition and fail to initiate early treatment. A comprehensive management plan can be assembled through an "ABCDE" approach: "A" for assessment of cardiovascular risk and aspirin therapy, "B" for blood pressure control, "C" for cholesterol management, "D" for diabetes prevention and diet therapy, and "E" for exercise therapy. This ABCDE approach provides a practical and systematic framework for encouraging metabolic syndrome recognition and for implementing a comprehensive, evidence-based management plan for the reduction of cardiovascular risk.     

The metabolic syndrome, hyperlipidemia, and insulin resistance

The metabolic syndrome is a cluster of cardiovascular risk factors associated with obesity. The defining components of the metabolic syndrome, according to the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), are elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose. The pathophysiologic basis of metabolic syndrome is complex and reflects several interrelated disturbances of glucose and lipid homeostasis. Metabolic syndrome is prevalent in the United States and developed nations, and patients with this disorder are at risk for type 2 diabetes mellitus and cardiovascular disease, underscoring the need for prompt patient identification and management. The first-line approach to control of metabolic syndrome is weight control and exercise. A wide range of pharmacologic interventions (eg, statins, antihypertensive drugs, insulin sensitizers, and thiazolidinediones) have been shown to be effective in controlling the individual components of metabolic syndrome. Obesity, which is a necessary component of metabolic syndrome, has reached epidemic proportions in the United States. Although lifestyle management or medications can control the underlying risk factors and most of the components of metabolic syndrome, long-term weight loss is difficult to achieve. Several promising pharmacologic interventions that may have an important role in the management of metabolic syndrome by treating adipose tissue-mediated metabolic disturbances are in the early stages of development.     

Childhood weight and metabolic syndrome in adults.

Metabolic syndrome is a clustering of many insulin resistance-associated cardiovascular risk factors such as hypertension, hypertriglyceridaemia, low high-density lipoprotein (HDL) cholesterol, abnormal glucose metabolism and hyperinsulinaemia. Furthermore, it is known that obesity is the most common clinical state characterized by insulin resistance. Central adiposity, in particular, has been shown to be the most distinctive feature of this syndrome. Some studies have also suggested that obesity per se would be necessary for the expression of metabolic defects associated with centrally distributed fat. It has been presented that undernutrition in utero might 'programme' blood pressure, insulin resistance, blood coagulation and cholesterol metabolism and would thus have a role in the aetiology of cardiovascular disease and type 2 diabetes in adult life. Some studies have also found associations between low birthweight and metabolic syndrome in adulthood. However, criticism on this hypothesis of fetal programming has recently been presented. It has been suggested that the origins of adulthood risk of cardiovascular disease and type 2 diabetes can be related to somatic growth as a child, not necessarily to intrauterine growth. In westernized countries, the relative proportion of underweight newborn children is decreasing, and thus considering entire populations low birthweight has lost its theoretical role in the aetiology of type 2 diabetes and cardiovascular disease. On the other hand, as obesity is known to be increasing in the industrialized countries among all age groups, the association between weight gain in childhood and metabolic syndrome in adulthood is more than noteworthy. Instead of undernutrition during pregnancy, sedentary lifestyle and lack of physical exercise pose a new threat. This results in an increased occurrence of overweight in childhood, which may be the first sign of insulin resistance and future metabolic syndrome.     

Lifestyle modification and endothelial function in obese subjects

The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-α, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with either the metabolic syndrome or Type 2 diabetes.     

Lifestyle modification and endothelial function in obese subjects

The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-alpha, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with either the metabolic syndrome or Type 2 diabetes.     

The metabolic syndrome: metabolic changes with vascular consequences

Despite criticism regarding its clinical relevance, the concept of the metabolic syndrome improves our understanding of both the pathophysiology of insulin resistance and its associated metabolic changes and vascular consequences. Free fatty acids (FFA) and tumour necrosis factor-alpha (TNF-alpha) play prominent roles in the development of insulin resistance by impairing the intracellular insulin signalling transduction pathway. Obesity is an independent risk factor for cardiovascular disease and strongly related to insulin resistance. In case of obesity, FFAs and TNF-alpha are produced in abundance by adipocytes, whereas the production of adiponectin, an anti-inflammatory adipokine, is reduced. This imbalanced production of pro- and anti-inflammatory adipokines, as observed in adipocyte dysfunction, is thought to be the driving force behind insulin resistance. The role of several recently discovered adipokines such as resistin, visfatin and retinol-binding protein (RBP)-4 in the pathogenesis of insulin resistance is increasingly understood. Insulin resistance induces several metabolic changes, including hyperglycaemia, dyslipidaemia and hypertension, all leading to increased cardiovascular risk. In addition, the dysfunctional adipocyte, reflected largely by low adiponectin levels and a high TNF-alpha concentration, directly influences the vascular endothelium, causing endothelial dysfunction and atherosclerosis. Adipocyte dysfunction could therefore be regarded as the common antecedent of both insulin resistance and atherosclerosis and functions as the link between obesity and cardiovascular disease. Targeting the dysfunctional adipocyte may reduce the risk for both cardiovascular disease and the development of type 2 diabetes. Although lifestyle intervention remains the cornerstone of therapy in improving insulin sensitivity and its associated metabolic changes, medical treatment might prove to be important as well.     

Hepatic insulin resistance,metabolic syndrome and cardiovascular disease

BackgroundThe metabolic syndrome is a constellation of common metabolic disorders that is associated with cardiovascular disease. Insulin resistance has a central role in the pathophysiology of metabolic syndrome.Recent advancesIt is now commonly accepted that chronic inflammation associated with visceral obesity induces insulin resistance in the liver. Chronic inflammation is characterized by the production of abnormal adipokines and cytokines such as TNF-α, FFA, IL-1, IL-6, leptin and resistin. These factors inhibit insulin signalling in hepatocytes by activating SOCS proteins, several kinases such as JNK, IKK-β and PKC and protein tyrosine phosphatases such as PTP1B and PTEN, that in turn impair insulin signalling at insulin receptor and insulin receptor substrate (IRS) level. Hepatic insulin resistance in turn causes impaired suppression of glucose production by insulin in hepatocytes leading to hyperglycemia. An important and early complication of hepatic insulin resistance is the induction of hepatic VLDL production, via changes in the rate of apoB synthesis and degradation and de novo lipogenesis, or increased FFA flux from adipose tissue into the liver. Insulin resistance also stimulates the production of CRP and PAI-1, both markers of an inflammatory state. All metabolic abnormalities related to hepatic insulin resistance have been shown to directly or indirectly promote atherosclerosis. Hyperglycemia induces a series of alterations including endothelial dysfunction, cellular proliferation, changes in extracellular matrix conformation and impairment of LDL receptor-mediated uptake decreasing the in vivo clearance of LDL. Small dense LDLs associated with high circulating VLDL have higher affinity to the intimal proteoglycans leading to the penetration of more LDL particles into the arterial wall. CRP can also accelerate atherosclerosis by increasing the expression of PAI-1 and adhesion molecules in endothelial cells, inhibition of nitric oxide formation and increasing LDL uptake into macrophages.ConclusionsOverall, growing evidence suggests that hepatic insulin resistance is sufficient to induce several components of the metabolic syndrome and promote progression to cardiovascular disease. Many unresolved questions remain however on the molecular and cellular mechanisms that trigger hepatic insulin resistance and promote the development of clinical metabolic syndrome.     

Epidemiology and treatment of the metabolic syndrome

Recent definitions of the metabolic syndrome from the World Health Organization (WHO) and National Cholesterol Education Program (NCEP) have given us a clearer picture of the prevalence of the metabolic syndrome and the risks it poses for cardiovascular disease and type 2 diabetes. Solid epidemiological and trial evidence support lifestyle changes as the main modifiable risk factors, including abdominal obesity, sedentary lifestyle and a diet rich in saturated fat and low in fiber content, in the treatment of individual components of the metabolic syndrome. Physical activity may prevent the metabolic syndrome as defined by the WHO and NCEP, but the evidence for lifestyle changes using these definitions is still sparse. No trials on the treatment of the metabolic syndrome to prevent diabetes have been published. However, both the Finnish Diabetes Prevention Study and the Diabetes Prevention Program found that moderate lifestyle interventions in persons with impaired glucose tolerance, a condition related to the metabolic syndrome. decreased the incidence of type 2 diabetes by 58%. Some drugs may also prevent diabetes. Further research on lifestyle modifications in the prevention and treatment of the metabolic syndrome, and on how best to promote lifestyle changes, is needed. In the meantime, efforts to curb obesity and overweight, increase physical activity and improve compliance with current dietary recommendations should continue.     

Identification of the metabolic syndrome and imaging of subclinical coronary artery disease: early markers of cardiovascular risk

The metabolic syndrome and imaging of subclinical coronary artery disease are novel approaches to identify cardiovascular risk at an early disease stage before the onset of complications. The metabolic syndrome is defined as a combination of major and emerging cardiovascular risk factors that are related to underlying insulin resistance. These risk factors accelerate atherosclerotic disease progression and increase the risk for future cardiovascular events. Atherosclerosis imaging visualizes the presence of subclinical disease burden many years before the onset of symptoms. The early identification of asymptomatic persons with increased cardiovascular risk provides the opportunity to prevent of future disease complications. The relationship between the metabolic syndrome and sublinical disease burden is incompletely understood. Although further evaluation of the potential role for the emerging biomarkers and imaging techniques in the setting of the metabolic syndrome is needed, it is obvious that cardiovascular nurses need to develop a heightened awareness of patients at risk for future events.     

Calculating insulin resistance in the primary care setting: why should we worry about insulin levels in euglycemic patients?

PURPOSE: To describe measures that would determine which patients are insulin resistant and at risk for the metabolic syndrome and its sequelae cardiovascular diseases (CVD) and to analyze methods to determine the presence of insulin resistance and the advantages or disadvantages of each. DATA SOURCES: Review of the multidisciplinary clinical and research literature. CONCLUSIONS: Insulin resistance occurs early in the trajectory of the metabolic syndrome, making it a prime candidate for timely interventions to reduce risk for both type 2 diabetes and CVD. Therefore, prompt recognition of insulin resistance prior to the development of the full metabolic syndrome, type 2 diabetes, and/or CVD may assist in the prevention of morbidity and premature mortality. Likewise, because many insulin-resistant patients belong to minority racial groups (i.e., African American, Hispanic, Native American, or Pacific Islanders), early identification may have a positive impact on the reduction of cardiovascular health disparities. IMPLICATIONS FOR PRACTICE: Documenting the presence of insulin resistance will assist the practitioner to determine if a low-risk patient is in jeopardy for development of type 2 diabetes and/or CVD. Early cardiovascular risk identification is important to clinical practice as it allows more time for the practitioner to counsel patients for the essential planning needed to make lifestyle changes.     

Comprehensive management of cardiometabolic risk factors

Comprehensive management of cardiometabolic risk requires management of a patient's underlying risk factors. The initial approach to treatment demands a careful assessment of patient risk, using formal risk assessment tools (eg, the Framingham Risk Score and the National Cholesterol Education Program Adult Treatment Panel III definition of metabolic syndrome), combined with comprehensive knowledge of the patient. There is increasing evidence that lifestyle modification and pharmacotherapy can delay or prevent the progression of insulin resistance to diabetes and cardiovascular disease. Periodic reassessment of a patient's risk can assist in guiding long-term therapy to achieve optimal cardiometabolic health.     

Epidemiology and treatment of the metabolic syndrome

Recent definitions of the metabolic syndrome from the World Health Organization (WHO) and National Cholesterol Education Program (NCEP) have given us a clearer picture of the prevalence of the metabolic syndrome and the risks it poses for cardiovascular disease and type 2 diabetes. Solid epidemiological and trial evidence support lifestyle changes as the main modifiable risk factors, including abdominal obesity, sedentary lifestyle and a diet rich in saturated fat and low in fiber content, in the treatment of individual components of the metabolic syndrome. Physical activity may prevent the metabolic syndrome as defined by the WHO and NCEP, but the evidence for lifestyle changes using these definitions is still sparse. No trials on the treatment of the metabolic syndrome to prevent diabetes have been published. However, both the Finnish Diabetes Prevention Study and the Diabetes Prevention Program found that moderate lifestyle interventions in persons with impaired glucose tolerance, a condition related to the metabolic syndrome, decreased the incidence of type 2 diabetes by 58%. Some drugs may also prevent diabetes. Further research on lifestyle modifications in the prevention and treatment of the metabolic syndrome, and on how best to promote lifestyle changes, is needed. In the meantime, efforts to curb obesity and overweight, increase physical activity and improve compliance with current dietary recommendations should continue.     

Early intervention to achieve optimal outcomes in type 2 diabetes: a case presentation

Type 2 diabetes mellitus (DM) is a progressive disease characterized by insulin resistance and impaired insulin secretion. To compensate for these metabolic dysfunctions, pancreatic beta-cells begin to overproduce insulin; however, it is this compensatory mechanism that eventually results in beta-cell exhaustion, impaired insulin secretion, and relative insulin deficiency. The metabolic abnormalities associated with diabetes also contribute to vascular dysfunction and an increased risk of coronary heart disease. Among patients with type 2 DM, cardiovascular disease, particularly macrovascular disease, is the primary cause of mortality, accounting for 55% of deaths. Management of the disease, therefore, must address all of the contributing factors, including a sedentary lifestyle and diet that contribute to overweight/obesity, and comorbidities such as hypertension and dyslipidemia. In this paper, we present a case study based on actual clinical experience to illustrate an evidence-based rationale for early and aggressive intervention for patients with type 2 DM, including lifestyle modification, oral antidiabetic agents, and insulin.     

Metabolic syndrome: definition and therapeutic implications

The collection of impaired glucose metabolism, central obesity, elevated blood pressure, and dyslipidemia is identified as metabolic syndrome (MetS). It is estimated that approximately 25% of the world's population has MetS. In the United States, MetS is more common in men and Hispanics, and its incidence increases with age. Metabolic syndrome increases the risk of developing cardiovascular disease and type 2 diabetes mellitus. The underlying risk factors include insulin resistance and abdominal obesity. Confusion about MetS exists in part due to the lack of a consensus definition and treatment protocol. Treatment of MetS begins with therapeutic lifestyle changes and then pharmacologic treatment of the syndrome's individual components. Effective interventions include diet modification, exercise, and use of pharmacologic agents to treat risk factors. Weight loss and increasing physical activity significantly improve all aspects of MetS. A diet that includes more fruits, vegetables, whole grains, monounsaturated fats, and low-fat dairy products will benefit most patients with MetS. Physicians can be most effective in advising patients by customizing specific lifestyle recommendations after assessing patients for the presence of risk factors.     

The metabolic syndrome: concepts and controversy

The metabolic syndrome is an insulin-resistant state characterized by a cluster of cardiovascular risk factors, including various combinations of abdominal obesity, glucose intolerance, hypertension, and atherogenic dyslipidemia (elevated triglyceride values, low high-density lipoprotein cholesterol levels, and small dense low-density lipoprotein cholesterol particles). The current epidemic of obesity and physical inactivity has led to an increased prevalence of this disorder. In this review, we discuss the history and pathogenesis of the metabolic syndrome, the controversy regarding the appropriateness of considering it a distinct diagnosis, and the importance of lifestyle modification in its prevention and treatment. The need for all cardiovascular risk factors to be treated, whether or not they are components of the metabolic syndrome, is emphasized. Recent discussions in the literature regarding the continued use of the term metabolic syndrome should be considered a healthy academic debate that hopefully will stimulate Ideas and innovative research to improve patient care.     

精神分裂症患者伴发代谢综合征非药物干预的研究进展

精神分裂症伴发代谢综合征患病率远高于普通人群,合并代谢综合征不仅增加患者罹患心血管疾病的风险,还可能会加重精神疾病症状和增加复发的风险,甚至威胁到生命,影响患者的社会功能,增加额外的个人和社会医疗负担。本文归纳了精神分裂症发生代谢综合征的相关因素,包括药物因素、生活方式及饮食因素、认知因素等,阐述了相应的不同护理干预模式,旨在为提升精神分裂症护理质量提供参考,积极预防和控制代谢综合征发生的危险因素。