Metabolic syndrome
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.
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:
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 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.
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 ATPIII definition. According to Dr. Scott Grundy, University of Texas Southwestern Medical School, Dallas, Texas, the intent was just to update the NCEP ATPIII definition and not create a new definition (personal communication):
- 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 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. The most important factors in order are 1) aging, 2) lifestyle (i.e., physical activity and caloric intake) and 3) genetics. 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 a variety of causes including dietary fructose mediated increased uric acid levels.[3][4][5]
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 [6]. The progression from visceral fat to increased TNFα to insulin resistance parallels human development of metabolic syndrome.
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 not FDA approved.
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.[7][8]
- 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.[9]
- 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.[10]
- 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.[11]
- The same year, Singer used the term for associations of obesity, gout, diabetes mellitus, and hypertension with hyperlipoprotenemia.[12]
- 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.[13][14]
- 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.[15]
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
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.
External links
Citations
- [1] The IDF consensus worldwide definition of the metabolic syndrome. PDF
- [2] 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.
- [3] 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, A causal role for uric acid in fructose-induced metabolic syndrome, Am J Phys Renal Phys, Vol. 290, No. 3, pp. F625–F631, 2006, No. PMID 16234313.
- [4] Hallfrisch J, Metabolic effects of dietary fructose, FASEB J, Vol. 4, No. 9, pp. 2652–2660, 1990, No. PMID 2189777.
- [5] Reiser S, Powell AS, Scholfield DJ, Panda P, Ellwood KC, Canary JJ, Blood lipids, lipoproteins, apoproteins, and uric acid in men fed diets containing fructose or high-amylose cornstarch, Am J Clin Nutr, Vol. 49, No. 5, pp. 832–839, 1989, No. PMID 2497634.
- [6] http://www.ebmonline.org/cgi/content/full/229/6/486, Fukuchi S, Hamaguchi K, Seike M, Himeno K, Sakata T, Yoshimatsu H., Role of Fatty Acid Composition in the Development of Metabolic Disorders in Sucrose-Induced Obese Rats, Exp Biol Med, Vol. 229, No. 6, pp. 486–493, 2004, No. PMID 15169967.
- [7] Joslin EP. The prevention of diabetes mellitus. JAMA 1921;76:79–84.
- [8] Kylin E. [Studies of the hypertension-hyperglycemia-hyperuricemia syndrome] (German). Zentralbl Inn Med 1923;44: 105-27.
- [9] Vague J. La diffférenciacion sexuelle, facteur déterminant des formes de l'obésité. Presse Med 1947;30:339-40.
- [10] 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.
- [11] Haller H. [Epidemiology and associated risk factors of hyperlipoproteinemia] (German). Z Gesamte Inn Med 1977;32(8):124-8. PMID 883354.
- [12] Singer P. [Diagnosis of primary hyperlipoproteinemias] (German). Z Gesamte Inn Med 1977;32(9):129-33. PMID 906591.
- [13] Phillips GB. Sex hormones, risk factors and cardiovascular disease. Am J Med 1978;65:7-11. PMID 356599.
- [14] 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.
- [15] Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595-607. PMID 3056758.