Information about Metabolic Syndrome

Dysmetabolic syndrome X
Classification & external resources

ICD-9	277.7
OMIM	605552
DiseasesDB	31955
MeSH	D024821

Metabolic syndrome is a combination of medical disorders that increase one's risk for cardiovascular disease and diabetes. It affects a large number of people in a clustered fashion. In some studies, the prevalence in the USA is calculated as being up to 25% of the population. A condition with some similarities to human metabolic syndrome is recognised in horses, see equine metabolic syndrome. It is unknown if they have the same etiology.

It is known under various other names, such as (metabolic) syndrome X, insulin resistance syndrome, Reaven's syndrome or CHAOS (Australia).

Signs and symptoms

Symptoms and features are:

• Fasting hyperglycemia — diabetes mellitus type 2 or impaired fasting glucose, impaired glucose tolerance, or insulin resistance;
• High blood pressure;
• Central obesity (also known as visceral, male-pattern or apple-shaped adiposity), overweight with fat deposits mainly around the waist;
• Decreased HDL cholesterol;
• Elevated triglycerides;
• Elevated uric acid levels.

Associated diseases and signs are: fatty liver (especially in concurrent obesity), progressing to non-alcoholic fatty liver disease, polycystic ovarian syndrome, hemochromatosis (iron overload); and acanthosis nigricans (a skin condition featuring dark patches).

Diagnosis

There are currently two major definitions for metabolic syndrome provided by 1) International Diabetes Federation^[1] and 2) the revised National Cholesterol Education Program, respectively. The revised NCEP and IDF definitions of metabolic syndrome are very similar and it can be expected that they will identify many of the same individuals as having metabolic syndrome. The two differences are that IDF excludes any subject without increased waist circumference, while in the NCEP definition metabolic syndrome can be diagnosed based on other criteria and 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. These two definitions are much closer to each other than the original NCEP and WHO definitions.

WHO

The World Health Organization criteria (1999) require presence of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance, AND two of the following:

• blood pressure: ≥ 140/90 mmHg
• dyslipidaemia: triglycerides (TG): ≥ 1.695 mmol/L and/or high-density lipoprotein cholesterol (HDL-C) ≤ 0.9 mmol/L (male), ≤ 1.0 mmol/L (female)
• central obesity: waist:hip ratio > 0.90 (male), > 0.85 (female), and/or body mass index > 30 kg/m²
• microalbuminuria: urinary albumin excretion ratio ≥ 20 mg/min or albumin:creatinine ratio ≥ 30 mg/g

EGIR

European Group for the Study of Insulin Resistance (1999) requires insulin resistance defined as the top 25% of the fasting insulin values among non-diabetic individuals AND two or more of the following:

• central obesity: waist circumference ≥ 94 cm (male), ≥ 80 cm (female)
• dyslipidaemia: TG ≥ 2.0 mmol/L and/or HDL-C < 1.0 mg/dL or treated for dyslipidaemia
• hypertension: blood pressure ≥ 140/90 mmHg or antihypertensive medication
• fasting plasma glucose ≥ 6.1 mmol/L

NCEP

The National Cholesterol Education Program Adult Treatment Panel III (2001) requires at least three of the following:^[2]

• central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 36 inches(female)
• dyslipidaemia: TG ≥ 1.695 mmol/L (150 mg/dl)
• dyslipidaemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female)
• blood pressure ≥ 130/85 mmHg
• fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dl)

American Heart Association/Updated NCEP

There is quite a bit of confusion about whether AHA/NHLBI intended to create another set of guidelines or simply update the NCEP ATP III definition. According to Scott Grundy, University of Texas Southwestern Medical School, Dallas, Texas, the intent was just to update the NCEP ATP III definition and not create a new definition.^[3]:

• Elevated waist circumference: Men — Equal to or greater than 40 inches (102 cm) Women — Equal to or greater than 35 inches (88 cm)
• Elevated triglycerides: Equal to or greater than 150 mg/dL
• Reduced HDL (“good”) cholesterol: Men — Less than 40 mg/dL Women — Less than 50 mg/dL
• Elevated blood pressure: Equal to or greater than 130/85 mm Hg or use of medication for hypertension
• Elevated fasting glucose: Equal to or greater than 100 mg/dL (5.6 mmol/L) or use of medication for hyperglycemia

Etiology

The cause of the metabolic syndrome is unknown. The pathophysiology is extremely complex and has only been partially elucidated. Most patients are older, obese, sedentary, and have a degree of insulin resistance. The most important factors in order are 1) aging, 2) genetics and 3) lifestyle (i.e., decreased physical activity and excess caloric intake). There is debate regarding whether obesity or insulin resistance is the cause of the metabolic syndrome or if it is a by-product of a more far-reaching metabolic derangement. Systemic inflammation: a number of inflammatory markers (including C-reactive protein) are often increased, as are fibrinogen, interleukin 6 (IL−6), Tumor necrosis factor-alpha (TNFα) and others. Some have pointed to oxidative stress due to a variety of causes including dietary fructose mediated increased uric acid levels.^[4][5][6]

Pathophysiology

Commonly, there is development of visceral fat followed by the adipocytes (fat cells) of the visceral fat increasing plasma levels of TNFα and altering levels of a number of other substances (e.g., adiponectin, resistin, PAI-1). TNFα has been shown to not only cause the production of inflammatory cytokines, but may also trigger cell signalling by interaction with a TNFα receptor that may lead to insulin resistance . An experiment with rats that were fed a diet one-third of which was sucrose has been proposed as a model for the development of the metabolic syndrome. The sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance ^[7]. The progression from visceral fat to increased TNFα to insulin resistance has some parallels to human development of metabolic syndrome.

Therapy

The first line treatment is change of lifestyle (i.e., caloric restriction and physical activity). However, drug treatment is frequently required. Generally, the individual diseases that comprise the metabolic syndrome are treated separately (e.g. diuretics and ACE inhibitors for hypertension). Cholesterol drugs may be used to lower LDL cholesterol and triglyceride levels, if they are elevated, and to raise HDL levels if they are low. Use of drugs that decrease insulin resistance e.g., metformin and thiazolidinediones is controversial and not FDA approved.

A recent study indicated that cardiovascular exercise was therapeutic in approximately 31% of cases. The most probable benefit was to triglyceride levels, with 43% showing improvement; conversely 91% of test subjects did not exhibit a decrease in fasting plasma glucose or insulin resistance.^[8] Many other studies have supported the value of increased physical activity along with restricted calories in metabolic syndrome.

Prevention

Various strategies have been proposed to prevent the development of metabolic syndrome. These include increased physical activity (such as walking 30 minutes every day),^[9] and a healthy, reduced calorie diet.^[10] There are many studies that support the value of a healthy lifestyle as above. However, one study stated that these measures are effective in only a minority of people.<ref name="katzmaryk" /> The International Obesity Taskforce states that interventions on a sociopolitical level are required to reduce development of the metabolic syndrome in populations.^[11]

A 2007 study of 2,375 male subjects over 20 years suggested that daily intake of a pint of milk or equivalent dairy products more than halved the risk of metabolic syndrome.^[12] Other studies both support and dispute the authors' findings.^[13]

History

The term "metabolic syndrome" dates back to at least the late 1950s, but came into common usage in the late 1970s to describe various associations of risk factors with diabetes, that had been noted as early as the 1920s.^[14][15]

• The Marseilles physician Dr. Jean Vague, in 1947, made the interesting observation that upper body obesity appeared to predispose to diabetes, atherosclerosis, gout, and calculi.^[16]
• Avogaro, Crepaldi and co-workers described six moderately obese patients with diabetes, hypercholesterolemia, and marked hypertriglyceridemia all of which improved when the patients were put on a hypocaloric, low carbohydrate diet.^[17]
• In 1977, Haller used the term "metabolic syndrome" for associations of obesity, diabetes mellitus, hyperlipoproteinemia, hyperuricemia and steatosis hepatis when describing the additive effects of risk factors on atherosclerosis.^[18]
• The same year, Singer used the term for associations of obesity, gout, diabetes mellitus, and hypertension with hyperlipoprotenemia.^[19]
• In 1977 and 1978, Gerald B. Phillips developed the concept that risk factors for myocardial infarction concur to form a "constellation of abnormalities" (i.e., glucose intolerance, hyperinsulinemia, hyperlipidemia [hypercholesterolemia and hypertriglyceridemia] and hypertension) that is associated not only with heart disease, but also with aging, obesity and other clinical states. He suggested there must be an underlying linking factor, the identification of which could lead to the prevention of cardiovascular disease; he hypothesized that this factor was sex hormones.^[20][21]
• In 1988, in his 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.^[22]

The terms "metabolic syndrome," "insulin resistance syndrome," and "syndrome X" are now used specifically to define a constellation of abnormalities that is associated with increased risk for the development of type 2 diabetes and atherosclerotic vascular disease (e.g. heart disease and stroke).

See also

• Hyperinsulinemia
• Insulin resistance
• Chronic Somogyi rebound

References

External links

• ApolloLipids — resource for medical professionals providing articles and slides on metabolic syndrome concerning cardiovascular disease, lipids and obesity.
• American Heart Association's description of Syndrome X.