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Query: UMLS:C0948265 (metabolic syndrome)
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BACKGROUND AND THERAPY: The metabolic syndrome comprises a virulent and lethal group of atherosclerotic risk factors, including dyslipidemia, obesity, systemic hypertension and insulin resistance. The prevalence of the metabolic syndrome has continuously grown in industrialized and developing countries during the last decades, and affects tens of millions of people in Germany and Europe. Particularly prominent as a risk factor for the development of insulin resistance is central obesity, which is causally involved in the pathogenesis of insulin resistance in addition to genetic predisposition. The metabolic syndrome can easily be diagnosed in clinical practice (guidelines of the WHO and ATP III panel), and immediate treatment of the metabolic syndrome is mandatory because those patients are at increased risk to develop overt diabetes mellitus, coronary artery disease and stroke. The high risk for cardiovascular diseases is supported by findings that the risk for myocardial infarction in patients with insulin resistance is as high as the risk of patients after their first myocardial infarction. Intentional weight reduction reduces abdominal obesity and beneficially modulates all features of the metabolic syndrome, while the benefits of aerobic exercise training are discussed controversially. Thus, weight reduction causally undoes essential features of the metabolic syndrome, but effects are often not enduring. Therefore, the treatment of cardiovascular risk factors such as hypertension and dislipidemia is essential. Of note, antihypertensive treatment is more effective than tight glucose control to reduce cardiovascular events. Diuretics, ACE-inhibitors and angiotensin II type 1 receptor antagonists are suggested as first line therapeutics. However, at least two antihypertensives are usually necessary to achieve the suggested goals of blood pressure reduction. In conclusion, the prevalence of the metabolic syndrome is continuously growing. Due to its adverse impact on cardiovascular disease, early detection and aggressive treatment is mandatory to ensure longlasting benefits for affected patients.
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PMID:[Arterial hypertension and metabolic syndrome]. 1468 1

With the increased attention being given to cardiovascular risk factor reduction, the opportunity exists to substantially decrease the largest cause of mortality in diabetic patients. The concept that type 2 diabetes and CVD are linked via a common etiologic pathway (metabolic syndrome) has substantial ramifications for the care of individual patients. Many of the metabolic abnormalities that contribute to both glycemic disorders and CVD are interrelated. For example, hyperinsulinemia and insulin resistance coupled with abdominal obesity further worsens HTN and hyperlipidemia. Likewise, the procoagulant state and endothelial dysfunction increase with worsening glycemic control. Specific interventions include tobacco cessation, a food management and physical activity plan, choice of antidiabetic agent (such as metformin), and use of ACE inhibitors for hypertension and microalbuminuria (Table 5). Programs to enhance cardiovascular risk factor reduction as part of the comprehensive evaluation and management of diabetic patients have been described [95,99]. One community-based program provided free screening to diabetic patients with randomization to either annotated result reports provided to the patient and their physician or results provided by a project nurse (either face-to-face or over the phone). Greater improvements in mean glycohemoglobin, cholesterol, and blood pressure were noted with verbal presentation of results [99]. Recent data from the Centers for Disease Control and Prevention Diabetes Cost-effectiveness Group support the idea that interventions to decrease CVD in diabetics are economically beneficial. Intensive management of hypertension, glycemic control, and hyperlipidemia each improved health outcomes. Hypertension control reduced costs. Although intensive treatment of glucose and hyperlipidemia increased costs, the increase was comparable to that of other frequently used health care interventions [100]. Further directions include further exploration of the implications and management of metabolic syndrome as it relates to CVD prevention. Interventions such as exercise, which can impact on all outcomes, require special attention. Efforts by physicians, health systems, and society are necessary to increase physical activity for individuals of all ages. It makes clinical sense that the recommendations for prevention of CVD in diabetics described in this article may also benefit patients with prediabetes (fasting glucose 110-125 mg/dl), but this remains to be definitively shown.
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PMID:Preventing cardiovascular disease in diabetes and glucose intolerance: evidence and implications for care. 1469 2

The metabolic syndrome (MS) is linked to cardiovascular risk. Recently, the Adult Treatment Panel (ATP) III provided new criteria for the definition of the MS. We analyzed the impact of the MS on cardiac structure and function and the independent association of the 5 different components of the ATP III-defined MS with cardiac markers of preclinical disease. Echocardiographic examination was performed in 612 nondiabetic participants with ATP III-defined MS and in 824 participants without the MS. Participants with the MS were more often women (p <0.001) and had similar ages compared with those without the MS. After controlling for confounders, participants with the MS had greater left ventricular (LV) dimension, mass, and relative wall thickness, and left atrial diameter (all p </=0.01), and a higher prevalence of LV hypertrophy (p <0.001), with lower ejection fraction (p <0.05), midwall shortening (p <0.001), and mitral E/A ratio (p <0.05) than participants who did not have the MS. In multiple regression modeling, high blood pressure (BP) and abdominal obesity were the only components of the MS associated with increased LV diameter; only high BP was associated with increased LV mass and prevalence of LV hypertrophy (both p <0.001). When high to normal BP was present in the absence of hypertension, the MS exhibited LV geometry similar to hypertensive participants without the MS. Therefore, abnormal LV geometry and function are related to the MS. Increased BP is the component of the MS most strongly associated with cardiac markers of preclinical disease, even in the absence of traditionally defined hypertension.
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PMID:Comparison of cardiac structure and function in American Indians with and without the metabolic syndrome (the Strong Heart Study). 1469 63

Elevated cortisol in a subset of depressed patients is an enduring and well-replicated finding. Much interest has focused on the possible effects of depression on the hippocampus; however, an emerging body of evidence suggests an association between depression and non-central nervous system illnesses. In this review, data on the effects of depression on the brain and other organ systems sensitive to elevated cortisol are discussed. From searches of the MEDLINE, PSYCHINFO, and Current Contents databases, and other sources, articles were found specifically related to depression and physical changes or medical conditions associated with corticosteroid excess in patients with Cushing's disease, including cognitive impairment, hippocampal atrophy, increased waist-to-hip ratio, bone loss, hypertension, diabetes, peptic ulcers, and hyperlipidemia. Data are strongest for a relationship between elevated cortisol and depression, hippocampal atrophy, cognitive impairment, abdominal obesity, and loss of bone density. Some evidence suggests an association between depression and hypertension, peptic ulcers, and diabetes. Depression does not appear to be associated with hyperlipidemia. The data provide some support for similar health effects in depressed patients and patients with Cushing's disease or the metabolic syndrome; however, additional studies are needed relating systemic effects of depression to cortisol. Limitations of the current literature, treatment implications, and possible directions for future research are discussed.
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PMID:Association of depression with medical illness: does cortisol play a role? 1470 19

The metabolic syndrome (MS) is a frequent cause of coronary artery disease (CAD), and recently the National Cholesterol Education Program Adult Treatment Panel III suggested its diagnosis in the presence of 3 to 5 quantitatively defined markers. Because the consequences of the MS are likely related to the number and diversity of markers, we studied the relation between the number of markers-the MS score-and the degree of abdominal obesity, risk factor profile, and severity of CAD. One thousand one hundred eight subjects of a mostly white population with symptoms of CAD (793 men and 315 women; 58.1 +/- 9.8 years of age) were divided into 6 groups based on their MS scores. A low high-density lipoprotein cholesterol level was the most frequently observed marker, followed by increased blood pressure, triglycerides, waist circumference, and fasting glucose. As the MS score increased so did abdominal obesity, parameters of "nontraditional" dyslipidemia with surrogate markers of dense low-density lipoprotein and high-density lipoprotein particles, blood pressure, fasting glucose, insulin, and the homeostatic model assessment insulin resistance index. Similarly, an increasing MS score was significantly related to more severe coronary angiographic alterations and higher frequencies of unstable angina, myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting. Therefore, the MS score provides a clinically useful index of MS severity and the associated atherosclerotic risk factor profile. It also correlates with the angiographic severity of CAD and its clinical complications.
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PMID:Effect of increasing metabolic syndrome score on atherosclerotic risk profile and coronary artery disease angiographic severity. 1471 40

The prevalence of the metabolic syndrome is highest among Hispanic adults. However, studies exploring the metabolic syndrome in overweight Hispanic youth are lacking. Subjects were 126 overweight children (8-13 yr of age) with a family history for type 2 diabetes. The metabolic syndrome was defined as having at least three of the following: abdominal obesity, low high-density lipoprotein (HDL) cholesterol, hypertriglyceridemia, hypertension, and/or impaired glucose tolerance. Insulin sensitivity was determined by the frequently sampled iv glucose tolerance test and minimal modeling. The prevalence of abdominal obesity, low HDL cholesterol, hypertriglyceridemia, systolic and diastolic hypertension, and impaired glucose tolerance was 62, 67, 26, 22, 4, and 27%, respectively. The presence of zero, one, two, or three or more features of the metabolic syndrome was 9, 22, 38, and 30%, respectively. After controlling for body composition, insulin sensitivity was positively related to HDL cholesterol (P < 0.01) and negatively related to triglycerides (P < 0.001) and systolic (P < 0.01) and diastolic blood pressure (P < 0.05). Insulin sensitivity significantly decreased (P < 0.001) as the number of features of the metabolic syndrome increased. In conclusion, overweight Hispanic youth with a family history for type 2 diabetes are at increased risk for cardiovascular disease and type 2 diabetes, and this appears to be due to decreased insulin sensitivity. Improving insulin resistance may be crucial for the prevention of chronic disease in this at-risk population.
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PMID:The metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity. 1471 36

The metabolic syndrome, recognized by the co-occurrence of general or abdominal obesity, hypertension, dyslipidemia, insulin resistance, and dysglycemia, appears to involve disturbances in metabolism, autonomic function, and health-related behaviors. However, physiological processes linking the components of the metabolic syndrome remain obscure. The current study examined associations of central nervous system serotonergic function with each metabolic syndrome risk variable, the metabolic syndrome, and physical activity. The subjects were 270 adult volunteers who participated in a study of cardiovascular disease risk factors and neurobehavioral functioning. Central serotonergic responsivity was indexed as the prolactin (PRL) response evoked by the serotonin-releasing agent, fenfluramine. Across the sample, low PRL response was associated with greater body mass index, higher concentrations of triglycerides, glucose, and insulin, higher systolic and diastolic blood pressure, greater insulin resistance, and less physical activity (P < 0.03-0.001). There also existed an inverse linear relationship between PRL response and the number of metabolic syndrome risk factors individuals possessed (P for trend = 0.002). Finally, a 1 SD decline in PRL response was associated with an odds ratio for the metabolic syndrome of 2.05 (95% confidence interval, 1.10-3.83; P = 0.002) and 5.70 (95% confidence interval, 1.69-19.25; P = 0.005), according to the definitions of the National Cholesterol Education Program and the World Health Organization, respectively. These findings reveal a heretofore unrecognized association between reduced central serotonergic responsivity and the metabolic syndrome.
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PMID:Low central nervous system serotonergic responsivity is associated with the metabolic syndrome and physical inactivity. 1471 60

In many industrialized nations, obesity is now considered an epidemic, resulting in accelerated morbidity and mortality. Obesity is associated with an increased risk of coronary artery disease as well as the metabolic syndrome comprising abdominal obesity, increased fasting blood glucose levels, dyslipidemia and hypertension, which are all recognized cardiovascular risk factors. Diet, exercise, and lifestyle changes constitute important recommendations for treatment. Unfortunately, although effective in some individuals, these recommendations have proven to be ineffective in adequately addressing the broad, enlarging scope of this public health problem. Drug treatment is often indicated but is somewhat limited by the minimal number of well tolerated drugs that have proven to have long-term efficacy in maintaining bodyweight loss. For example, phentermine may result in modest bodyweight loss through suppression of appetite, but potential cardiovascular adverse effects exist and the efficacy is mainly short-term. Sibutramine, an inhibitor of serotonin and norepinephrine (noradrenaline) reuptake, may increase satiety and result in modest bodyweight loss. However, cardiovascular adverse effects may occur in susceptible patients. Nonetheless, sibutramine is one of the few drugs that has been approved by the US Food and Drug Administration (FDA) for bodyweight loss. Orlistat, a lipase inhibitor, is also approved by the FDA for bodyweight loss but may have bothersome gastrointestinal adverse effects, especially among patients who do not adhere to the recommended low-fat diet. Ongoing studies continue to evaluate other drug treatments that may result in bodyweight reduction through a number of different mechanisms. It is anticipated that the development of effective and well tolerated antiobesity drugs will elevate the pharmacologic treatment of obesity to the status of other cardiovascular risk factors and metabolic disorders. This may be especially important given that dyslipidemia, hypertension and type 2 diabetes mellitus are often secondary to, or exacerbated by, obesity.
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PMID:Pharmacotherapy of obesity: currently marketed and upcoming agents. 1472 70

The highly prevalent metabolic syndrome (insulin resistance, type 2 diabetes, dyslipidemia, hypertension, along with abdominal obesity) resembles Cushing's syndrome. However, in simple obesity, plasma cortisol levels are not elevated. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), at least in mature adipocytes and hepatocytes, converts inactive circulating 11-keto steroids into active glucocorticoids, amplifying local glucocorticoid action. 11beta-HSD1 is elevated in adipose tissue in obese humans and rodents, suggesting that adipose tissue glucocorticoid excess may explain the conundrum. Indeed, transgenic mice overexpressing 11beta-HSD1 in adipose tissue faithfully replicate the metabolic syndrome. Conversely, 11beta-HSD1(-/-) mice resist the metabolic consequences of stress and high-fat feeding via insulin sensitisation and other advantageous effects in the liver and adipose tissue. Adipose 11beta-HSD1 deficiency contributes to a protective metabolic phenotype, supporting its role as a therapeutic target for the metabolic syndrome.
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PMID:Glucocorticoids and 11beta-hydroxysteroid dehydrogenase in adipose tissue. 1474 10

The metabolic syndrome is a compilation of factors characterized by insulin resistance and the identification of 3 of the 5 criteria of abdominal obesity, elevated triglycerides, decreased high-density lipoprotein (HDL) level, elevated blood pressure, and elevated fasting plasma glucose. According to census data from 2000, these criteria have lead to the diagnosis of approximately 47 million Americans with the metabolic syndrome, correlating with the 61% increase in the incidence of obesity between 1991 and 2000. Insulin resistance occurs when target tissues cannot respond properly to normal concentrations of insulin. The results are hypercoagulability, endothelial dysfunction, inflammation, and eventually coronary artery disease. Treatment involves lifestyle modification, including diet and exercise, to treat obesity and prevent the development of diabetes. Patients who meet the criteria for the metabolic syndrome may also be treated with insulin-sparing and insulin-sensitizing medications that help to improve endothelial function, vascular reactivity, and vascular inflammation. Ultimately, treatment goals are to prevent cardiovascular disease by both altering the risk factors that are components of the syndrome, and treating the lifestyle issues inherent to the disease process, such as caloric restriction and increased physical activity. There are 2 million more women than men in the United States categorized as being obese, with the trend of obesity and diabetes increasing. In the last decade there has been a 74% increase in obesity, mostly in women. This epidemic needs to be understood and managed to prevent further morbidity and mortality owing to diabetes and cardiovascular disease.
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PMID:The metabolic syndrome: an emerging health epidemic in women. 1496 55


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