Metabolic syndrome: Difference between revisions

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'''Metabolic syndrome''' is a clustering of at least three of the following five medical conditions: [[abdominal obesity]], [[hypertension|high blood pressure]], [[hyperglycemia|high blood sugar]], [[Hypertriglyceridemia|high serum triglycerides]], and low serum [[high-density lipoprotein]] (HDL).

Metabolic syndrome is associated with the risk of developing [[cardiovascular disease]] and [[Diabetes mellitus type 2|type 2 diabetes]]. In the U.S., about 25% of the adult population has metabolic syndrome, a proportion increasing with age, particularly among racial and ethnic minorities.

[[Insulin resistance]], metabolic syndrome, and [[prediabetes]] are closely related to one another and have overlapping aspects. The [[syndrome]] is thought to be caused by an underlying disorder of energy utilization and storage, but the cause of the syndrome is an area of ongoing [[medical research]]. Researchers debate whether a diagnosis of metabolic syndrome implies differential treatment or increases risk of [[cardiovascular disease]] beyond what is suggested by the sum of its individual components.

The key sign of metabolic syndrome is [[central obesity]], also known as visceral, male-pattern or apple-shaped adiposity. It is characterized by [[adipose tissue]] accumulation predominantly around the waist and trunk. Other signs of metabolic syndrome include high blood pressure, decreased fasting serum HDL cholesterol, elevated fasting serum [[triglyceride]] level, [[impaired fasting glucose]], insulin resistance, or prediabetes. Associated conditions include [[hyperuricemia]]; [[fatty liver]] (especially in concurrent [[obesity]]) progressing to [[nonalcoholic fatty liver disease]]; [[polycystic ovarian syndrome]] in women and [[erectile dysfunction]] in men; and [[acanthosis nigricans]].

Neck circumference has been used as a surrogate simple and reliable index to indicate upper-body subcutaneous fat accumulation. Neck circumference of more than {{cvt|40.25|cm}} for men and more than {{cvt|35.75|cm}} for women are considered high-risk for metabolic syndrome. Persons with large neck circumferences have a more-than-double risk of metabolic syndrome. In adults with overweight/obesity, clinically significant weight loss may protect against COVID-19 and neck circumference has been associated with the risk of being mechanically ventilated in COVID-19 patients, with a 26% increased risk for each centimeter increase in neck circumference. Moreover, hospitalized COVID-19 patients with a "large neck phenotype" on admission had a more than double risk of death.

Metabolic syndrome can lead to several serious and chronic complications, including [[Type 2 diabetes|type-2 diabetes]], [[cardiovascular disease]]s, [[stroke]], [[kidney disease]] and [[Non-alcoholic fatty liver disease|nonalcoholic fatty liver disease.]]

Furthermore, metabolic syndrome is associated with a significantly increased risk of surgical complications across most types of surgery in a 2023 systematic review and meta-analysis of over 13 million individuals.

The mechanisms of the complex pathways of metabolic syndrome are under investigation. The [[pathophysiology]] is very complex and has been only partially elucidated. Most people affected by the condition are older, obese, sedentary, and have a degree of insulin resistance. [[Stress (biology)|Stress]] can also be a contributing factor. The most important [[risk factors]] are diet (particularly sugar-sweetened beverage consumption), genetics, aging, sedentary behavior or low physical activity, disrupted [[chronobiology]]/sleep, mood disorders/psychotropic medication use, and excessive alcohol use. The pathogenic role played in the syndrome by the excessive expansion of adipose tissue occurring under sustained [[overeating]], and its resulting [[lipotoxicity]] was reviewed by [[Antonio Vidal-Puig|Vidal-Puig]].

There is debate regarding whether obesity or insulin resistance is the cause of the metabolic syndrome or if they are consequences of a more far-reaching metabolic derangement. Markers of systemic [[inflammation]], including [[C-reactive protein]], are often increased, as are [[fibrinogen]], [[interleukin 6]], [[tumor necrosis factor-alpha]]&nbsp;(TNF-α), and others. Some have pointed to a variety of causes, including increased [[uric acid]] levels caused by dietary [[fructose]].

Research shows that Western diet habits are a factor in development of metabolic syndrome, with high consumption of food that is not biochemically suited to humans. Weight gain is associated with metabolic syndrome. Rather than total adiposity, the core clinical component of the syndrome is visceral and/or ectopic fat (i.e., fat in organs not designed for fat storage) whereas the principal metabolic abnormality is insulin resistance. The continuous provision of energy via dietary [[Carbohydrate metabolism|carbohydrate]], [[Lipid metabolism|lipid]], and [[Protein metabolism|protein]] fuels, unmatched by physical activity/energy demand, creates a backlog of the products of [[Oxidative phosphorylation|mitochondrial oxidation]], a process associated with progressive mitochondrial dysfunction and insulin resistance.

Recent research indicates prolonged [[chronic stress]] can contribute to metabolic syndrome by disrupting the hormonal balance of the [[hypothalamic-pituitary-adrenal axis]] (HPA-axis). A dysfunctional HPA-axis causes high [[cortisol]] levels to circulate, which results in raising [[glucose]] and [[insulin]] levels, which in turn cause insulin-mediated effects on adipose tissue, ultimately promoting [[visceral adiposity]], insulin resistance, dyslipidemia and hypertension, with direct effects on the bone, causing "low turnover" [[osteoporosis]]. HPA-axis dysfunction may explain the reported risk indication of abdominal obesity to [[cardiovascular disease]] (CVD), type 2 diabetes and [[stroke]]. [[Psychosocial]] stress is also linked to heart disease.

Central obesity is a key feature of the syndrome, as both a sign and a cause, in that the increasing adiposity often reflected in high [[waist circumference]] may both result from and contribute to insulin resistance. However, despite the importance of obesity, affected people who are of normal weight may also be insulin-resistant and have the syndrome.

Physical inactivity is a predictor of CVD events and related [[Death|mortality]]. Many components of metabolic syndrome are associated with a [[sedentary lifestyle]], including increased adipose tissue (predominantly central); reduced HDL cholesterol; and a trend toward increased triglycerides, blood pressure, and glucose in the genetically susceptible. Compared with individuals who watched television or videos or used their computers for less than one hour daily, those who carried out these behaviors for greater than four hours daily have a twofold increased risk of metabolic syndrome.

Metabolic syndrome affects 60% of the U.S. population older than age 50. With respect to that demographic, the percentage of women having the syndrome is higher than that of men. The age dependency of the syndrome's prevalence is seen in most populations around the world.

{{main|Diabetes mellitus|Diabetes mellitus type 2}}

The metabolic syndrome quintuples the risk of type 2 diabetes mellitus. Type 2 diabetes is considered a [[complication (medicine)|complication]] of metabolic syndrome. In people with impaired glucose tolerance or impaired fasting glucose, presence of metabolic syndrome doubles the risk of developing type 2 diabetes. It is likely that prediabetes and metabolic syndrome denote the same disorder, defining it by the different sets of biological markers.

The presence of metabolic syndrome is associated with a higher prevalence of CVD than found in people with type 2 diabetes or [[impaired glucose tolerance]] without the syndrome. and is considered to be a risk factor for developing metabolic syndrome.

The approximate prevalence of the metabolic syndrome in people with [[coronary artery disease]] (CAD) is 50%, with a prevalence of 37% in people with premature coronary artery disease (age 45), particularly in women. With appropriate [[Cardiopulmonary rehabilitation|cardiac rehabilitation]] and changes in lifestyle (e.g., nutrition, physical activity, weight reduction, and, in some cases, drugs), the prevalence of the syndrome can be reduced.

[[Lipodystrophy|Lipodystrophic disorders]] in general are associated with metabolic syndrome. Both genetic (e.g., [[Berardinelli-Seip congenital lipodystrophy]], [[Dunnigan familial partial lipodystrophy]]) and acquired (e.g., [[HIV]]-related lipodystrophy in people treated with [[highly active antiretroviral therapy]]) forms of lipodystrophy may give rise to severe insulin resistance and many of metabolic syndrome's components.

There is research that associates comorbidity with rheumatic diseases. Both [[psoriasis]] and [[psoriatic arthritis]] have been found to be associated with metabolic syndrome.

Metabolic syndrome is seen to be a comorbidity in up to 50 percent of those with [[chronic obstructive pulmonary disease]] (COPD). It may pre-exist or may be a consequence of the lung pathology of COPD.

It is common for there to be a development of [[visceral fat]], after which the [[adipocyte]]s (fat cells) of the visceral fat increase [[blood plasma|plasma]] levels of [[TNF-α]] and alter levels of other substances (e.g., [[adiponectin]], [[resistin]], and [[PAI-1]]). TNF-α has been shown to cause the production of inflammatory [[cytokine]]s and also possibly trigger cell signaling by interaction with a [[TNF receptor superfamily|TNF-α receptor]] that may lead to insulin resistance. An experiment with rats fed a diet with 33% [[sucrose]] has been proposed as a model for the development of metabolic syndrome. The sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance. The progression from visceral fat to increased TNF-α to insulin resistance has some parallels to human development of metabolic syndrome. The increase in adipose tissue also increases the number of immune cells, which play a role in inflammation. Chronic inflammation contributes to an increased risk of hypertension, atherosclerosis and diabetes.

The involvement of the [[endocannabinoid system]] in the development of metabolic syndrome is indisputable. Endocannabinoid overproduction may induce [[reward system]] dysfunction and cause [[executive dysfunction]]s (e.g., impaired delay discounting), in turn perpetuating unhealthy behaviors. The brain is crucial in development of metabolic syndrome, modulating peripheral carbohydrate and lipid metabolism.

Metabolic syndrome can be induced by overfeeding with sucrose or fructose, particularly concomitantly with high-fat diet. The resulting oversupply of [[omega-6 fatty acids]], particularly [[arachidonic acid]] (AA), is an important factor in the [[pathogenesis]] of metabolic syndrome. Arachidonic acid (with its precursor – [[linoleic acid]]) serves as a substrate to the production of inflammatory mediators known as [[eicosanoids]], whereas the arachidonic acid-containing compound [[diacylglycerol]] (DAG) is a precursor to the endocannabinoid [[2-arachidonoylglycerol]] (2-AG) while [[fatty acid amide hydrolase]] (FAAH) mediates the metabolism of [[anandamide]] into [[arachidonic acid]]. Anandamide can also be produced from [[N-Acylphosphatidylethanolamine|''N''-acylphosphatidylethanolamine]] via several pathways. Anandamide and 2-AG can also be hydrolized into arachidonic acid, potentially leading to increased [[eicosanoid]] synthesis.

As of 2023, the U.S. [[National Cholesterol Education Program]] Adult Treatment Panel III (2001) continues to be the most widely-used clinical definition. It requires at least three of the following:

* Central obesity: waist circumference ≥ 102&nbsp;cm or 40&nbsp;inches (male), ≥ 88&nbsp;cm or 35&nbsp;inches(female)

* Fasting plasma glucose ≥ 6.1&nbsp;mmol/L (110&nbsp;mg/dl)

The [[International Diabetes Federation]] Task Force on Epidemiology and Prevention; the [[National Heart, Lung, and Blood Institute]]; the [[American Heart Association]]; the [[World Heart Federation]]; the [[International Atherosclerosis Society]]; and the [[International Association for the Study of Obesity]] published an interim joint statement to harmonize the definition of the metabolic syndrome in 2009. According to this statement, the criteria for clinical diagnosis of the

metabolic syndrome are three or more of the following:

*Elevated fasting glucose (≥100&nbsp;mg/dL (5.55&nbsp;mmol/L)

This definition recognizes that the risk associated with a particular waist measurement will differ in different populations. However, for international comparisons and to facilitate the etiology, the organizations agree that it is critical that a commonly agreed-upon set of criteria be used worldwide, with agreed-upon cut points for different ethnic groups and sexes. There are many people in the world of mixed ethnicity, and in those cases, pragmatic decisions will have to be made. Therefore, an international criterion of overweight may be more appropriate than ethnic specific criteria of abdominal obesity for an anthropometric component of this syndrome which results from an excess lipid storage in adipose tissue, skeletal muscle and liver.

The report notes that previous definitions of the metabolic syndrome by the International Diabetes Federation (IDF) and the revised [[National Cholesterol Education Program]] (NCEP) are very similar, and they identify individuals with a given set of symptoms as having metabolic syndrome. There are two differences, however: the IDF definition states that if [[body mass index]] (BMI) is greater than 30&nbsp;kg/m², central obesity can be assumed, and waist circumference does not need to be measured.  However, this potentially excludes any subject without increased waist circumference if BMI is less than 30. Conversely, the NCEP definition indicates that metabolic syndrome can be diagnosed based on other criteria. Also, the IDF uses geography-specific cut points for waist circumference, while NCEP uses only one set of cut points for waist circumference regardless of geography.

The [[World Health Organization]] (1999)  requires the presence of any one of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance, AND two of the following:

* Blood pressure ≥ 140/90 mmHg

* [[Microalbuminuria]]: urinary albumin excretion ratio ≥ 20&nbsp;µg/min or albumin:creatinine ratio ≥ 30&nbsp;mg/g

The [http://www.egir.org/load.php?menu=public&page=http://www.egir.org/activity.html European Group for the Study of Insulin Resistance] (1999) requires that subjects have insulin resistance (defined for purposes of clinical practivality as the top 25% of the fasting insulin values among nondiabetic individuals) AND two or more of the following:

* Central obesity: waist circumference ≥ 94&nbsp;cm or 37 inches (male), ≥ 80&nbsp;cm or 31.5 inches (female)

* Fasting plasma glucose ≥ 6.1&nbsp;mmol/L (110&nbsp;mg/dL)

The Cardiometabolic index (CMI) is a tool used to calculate risk of type 2 diabetes, non-alcoholic fatty liver disease, and metabolic issues. It is based on calculations from waist-to-height ratio and triglycerides-to-HDL cholesterol ratio.

CMI can also be used for finding connections between cardiovascular disease and erectile dysfunction. When following an anti inflammatory diet (low-glycemic carbohydrates, fruits, vegetables, fish, less red meat and processed foods) the markers may drop resulting in a significant reduction in body weight and adipose tissue.

[[C-reactive protein|High-sensitivity C-reactive protein]] has been developed and used as a marker to predict coronary vascular diseases in metabolic syndrome, and it was recently used as a predictor for nonalcoholic fatty liver disease (steatohepatitis) in correlation with serum markers that indicated lipid and glucose metabolism. Fatty liver disease and steatohepatitis can be considered manifestations of metabolic syndrome, indicative of abnormal energy storage as fat in ectopic distribution.

Reproductive disorders (such as polycystic ovary syndrome in women of reproductive age), and erectile dysfunction or decreased total testosterone (low testosterone-binding globulin) in men can be attributed to metabolic syndrome.

Various strategies have been proposed to prevent the development of metabolic syndrome. These include increased [[physical activity]] (such as walking 30 minutes every day), and a healthy, reduced calorie diet.  Many studies support the value of a healthy lifestyle as above. However, one study stated these potentially beneficial measures are effective in only a minority of people, primarily because of a lack of compliance with lifestyle and diet changes. The [[International Obesity Taskforce]] states that interventions on a sociopolitical level are required to reduce development of the metabolic syndrome in populations.

The [[Caerphilly Heart Disease Study]] followed 2,375 male subjects over 20 years and suggested the daily intake of an Imperial [[pint]] (~568 mL) of milk or equivalent dairy products more than halved the risk of metabolic syndrome. Some subsequent studies support the authors' findings, while others dispute them. A systematic review of four [[randomized controlled trials]] said that, in the short term, a [[Paleolithic diet|paleolithic nutritional]] pattern improved three of five measurable components of the metabolic syndrome in participants with at least one of the components.

===Medications===

Generally, the individual disorders that compose the metabolic syndrome are treated separately. [[Diuretic]]s and [[ACE inhibitor]]s may be used to treat hypertension. Various cholesterol medications may be useful if LDL cholesterol, triglycerides, and/or HDL cholesterol is abnormal.

Dietary [[Low-carbohydrate diet|carbohydrate restriction]] reduces blood glucose levels, contributes to weight loss, and reduces the use of several medications that may be prescribed for metabolic syndrome.

{{Main|Epidemiology of metabolic syndrome}}

Approximately 20–25 percent of the world's adult population has the cluster of risk factors that is metabolic syndrome.  In 2000, approximately 32% of U.S. adults had metabolic syndrome. In more recent years that figure has climbed to 34%.

In young children, there is no consensus on how to measure metabolic syndrome since age-specific cut points and reference values that would indicate "high risk" have not been well established. A continuous cardiometabolic risk summary score is often used for children instead of a dichotomous measure of metabolic syndrome.

Other conditions and specific microbiome diversity seems to be associated with metabolic syndrome, with certain-degree of gender-specificity.

In 1921, Joslin first reported the association of diabetes with hypertension and hyperuricemia.

In 1923, Kylin reported additional studies on the above triad.

In the late 1950s, the term metabolic syndrome was first used.

In 1967, Avogadro, Crepaldi and coworkers described six moderately obese people with diabetes, [[hypercholesterolemia]], and marked [[hypertriglyceridemia]], all of which improved when the affected people were put on a hypocaloric, low-carbohydrate diet.

In 1977, Haller used the term ''metabolic syndrome'' for associations of obesity, diabetes mellitus, [[hyperlipoproteinemia]], [[hyperuricemia]], and [[hepatic steatosis]] when describing the additive effects of risk factors on atherosclerosis.

In 1988, in his [[Banting Lectures|Banting lecture]], [[Gerald M. Reaven]] proposed insulin resistance as the underlying factor and named the constellation of abnormalities syndrome X. Reaven did not include abdominal obesity, which has also been hypothesized as the underlying factor, as part of the condition.

* [[Metabolic disorder]]

* [[Portal-visceral hypothesis]]

{{Medical resources

|  ICD10          = E88.9

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{{二次利用|date=29 January 2024}}

{{DEFAULTSORT:Metabolic Syndrome}}