Metabolic syndrome

From Wikipedia, the free encyclopedia

**Dysmetabolic syndrome X**
*Classifications and external resources*
ICD-9	277.7
OMIM	605552
DiseasesDB	31955

Metabolic syndrome is a combination of medical disorders that affect 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, the end result of which is to increase one's risk for cardiovascular disease and diabetes.

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

1 Signs and symptoms
2 Diagnosis
3 Pathophysiology
4 Therapy
5 History
6 See also
7 References
8 External links

[edit] 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).

[edit] Diagnosis

There are several classifications for metabolic syndrome, by the WHO, International Diabetes Federation<ref>The IDF consensus worldwide definition of the metabolic syndrome. PDF</ref> and the 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 cutpoints for waist circumference, while NCEP uses only one set of cutpoints for waist circumference regardless of geography. These two definitions are much closer to each other than the original NCEP and WHO definitions.

[edit] 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

[edit] 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

[edit] NCEP

The National Cholesterol Education Program Adult Treatment Panel III (2001) requires at least three of the following:<ref>Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of 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). JAMA 2001;285:2486-97. PMID 11368702.</ref>

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

[edit] Pathophysiology

The causes of metabolic syndrome are extremely complex and have only been partially elucidated. Most patients are older, obese and have a degree of insulin resistance. There is debate regarding whether obesity or insulin resistance is the cause of the metabolic syndrome or 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 dietary fructose mediated increased uric acid levels.<ref>Nakagawa T, Hu H, Zharikov S, Tuttle KR, Short RA, Glushakova O, Ouyang X, Feig DI, Block ER, Herrera-Acosta J, Patel JM, Johnson RJ (2006). "A causal role for uric acid in fructose-induced metabolic syndrome". Am J Phys Renal Phys 290 (3): F625–F631. PMID 16234313.</ref><ref>Hallfrisch J (1990). "Metabolic effects of dietary fructose". FASEB J 4 (9): 2652–2660. PMID 2189777.</ref><ref>Reiser S, Powell AS, Scholfield DJ, Panda P, Ellwood KC, Canary JJ (1989). "Blood lipids, lipoproteins, apoproteins, and uric acid in men fed diets containing fructose or high-amylose cornstarch". Am J Clin Nutr 49 (5): 832–839. PMID 2497634.</ref>

Commonly, there is development of visceral fat followed by the adipocytes (fat cells) of the visceral fat increasing plasma levels of TNFα. 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 <ref>Fukuchi S, Hamaguchi K, Seike M, Himeno K, Sakata T, Yoshimatsu H. (2004). "Role of Fatty Acid Composition in the Development of Metabolic Disorders in Sucrose-Induced Obese Rats". Exp Biol Med 229 (6): 486–493. PMID 15169967.</ref>. Relevance of such studies for humans remains unclear.

[edit] Therapy

The main treatment is lifestyle (i.e., caloric restriction and physical activity). However, drug treatment may occasionally be necessary. 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. Use of drugs that decrease insulin resistance e.g., metformin and thiazolidinediones is controversial and generally not an approved use.

[edit] History

The term "metabolic syndrome" dates back to at least the late 1950's, but came into common usage in the late 1970's to describe various associations of risk factors with diabetes, that had been noted as early as the 1920's.<ref>Joslin EP. The prevention of diabetes mellitus. JAMA 1921;76:79–84.</ref><ref>Kylin E. [Studies of the hypertension-hyperglycemia-hyperuricemia syndrome] (German). Zentralbl Inn Med 1923;44: 105-27.</ref>

The Marseilles physician Dr. Jean Vague, in 1956, made the interesting observation that upper body obesity appeared to predispose to diabetes, atherosclerosis, gout, and calculi.<ref>Vague J. The degree of masculine differentiation of obesities: A factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am J Clin Nutr 1956;4:20-34. PMID 13282851.</ref>
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.<ref>Avogaro P, Crepaldi G, Enzi G, Tiengo A. Associazione di iperlipidemia, diabete mellito e obesità di medio grado. Acta Diabetol Lat 1967;4:572-590.</ref>
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.<ref>Haller H. [Epidemiology and associated risk factors of hyperlipoproteinemia] (German). Z Gesamte Inn Med 1977;32(8):124-8. PMID 883354.</ref>
The same year, Singer used the term for associations of obesity, gout, diabetes mellitus, and hypertension with hyperlipoprotenemia.<ref>Singer P. [Diagnosis of primary hyperlipoproteinemias] (German). Z Gesamte Inn Med 1977;32(9):129-33. PMID 906591.</ref>
In 1977 and 1978, Dr. 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.<ref>Phillips GB. Sex hormones, risk factors and cardiovascular disease. Am J Med 1978;65:7-11. PMID 356599.</ref><ref>Phillips GB. Relationship between serum sex hormones and glucose, insulin, and lipid abnormalities in men with myocardial infarction. Proc Natl Acad Sci U S A 1977;74:1729-1733. PMID 193114.</ref>
In 1988, in his Banting lecture, Dr. 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.<ref>Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595-607. PMID 3056758.</ref>

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).

[edit] See also

[edit] References

Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F. Diagnosis and Management of the Metabolic Syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2006;113(19):2363-72. PMID 16702489.
Grundy SM. Obesity, Metabolic Syndrome and Cardiovascular Disease. J Clin Endocrinol Metab 2004;89:2595-600. PMID 15181029.