Metabolic syndrome

From Citizendium
Jump to navigation Jump to search
This article is developing and not approved.
Main Article
Related Articles  [?]
Bibliography  [?]
External Links  [?]
Citable Version  [?]
Addendum [?]
This editable Main Article is under development and subject to a disclaimer.
Metabolic syndrome
OMIM 605552
MedlinePlus 0072903
MeSH D024821

The metabolic syndrome, also known as the dysmetabolic syndrome, metabolic syndrome X, or insulin resistance syndrome, is defined as "a cluster of metabolic risk factors for cardiovascular diseases and type 2 diabetes mellitus. The main components of metabolic syndrome X include excess abdominal fat; atherogenic dyslipidemia; hypertension; hyperglycemia; insulin resistance; a proinflammatory state; and a prothrombotic (thrombosis) state."[1]

"Although the metabolic syndrome has been defined in various ways, the ultimate importance of recognizing this combination of disorders is that it helps identify individuals at high risk for both type 2 diabetes and cardiovascular disease."[2]

The metabolic syndrome is a major public health concern worldwide as a particularly serious consequence of the global obesity epidemic [3], but the metabolic syndrome can be present in the absence of frank obesity. Almost one fourth of Americans have metabolic syndrome, and the proportion keeps raising.[4]

The metabolic syndrome is a serious disturbance of body metabolism and physiology, consisting of resistance of certain cell types of the body to the ability of the hormone insulin to promote the entry into cells of the energy-rich molecule, glucose, and two or more of the following abnormalities: high blood pressure (or use of drugs to control hypertension); high levels of serum triglycerides; low levels of high-density lipoprotein (HDL) cholesterol; overweight; detectable levels of the protein albumin in the urine (microalbuminuria). The abnormalities of triglyceride levels typically associate with other blood fat disturbances (dyslipidemia) that foster atherosclerosis (the buildup of plaques in artery walls that can lead to reduced blood flow to vital organs, including the heart) and to formation of blood clots that can break off and clog vital vessels to the brain, causing stroke. The biochemical factors that promote clot formation are also stimulated in the metabolic syndrome, and the syndrome appears to be one of a chronic state of inflammation, the typical body response to tissue injury.

Metabolic syndrome (MS) is a constellation of metabolic derangements associated with vascular endothelial dysfunction and oxidative stress and is widely regarded as an inflammatory condition, accompanied by an increased risk for cardiovascular disease.[5]

Diagnostic criteria

There are different clinical definitions of the metabolic syndrome; because of disagreement about the relative importance of insulin resistance in the cluster of risk factors, two definitions do not involve this risk factor.[6]

It is defined by the World Health Organisation using the following criteria:

  • Insulin resistance, identified by one of the following:
    • Type 2 diabetes
    • Impaired fasting glucose
    • Impaired glucose tolerance
    • or, for those with normal fasting glucose levels (<110mg/dL), glucose uptake below the lowest quartile for background population under investigation under hyperinsulinemic, euglycemic conditions
  • in conjunction with any two of the following:
    • Antihypertensive medication and/or high blood pressure (≥140mmHg systolic or ≥90mmHg diastolic)
    • Plasma triglycerides ≥150mg/dL (≥1.7mmol/L)
    • HDL cholesterol <35mg/dL (0.9mmol/L) in men or <39mg/dL (1.0mmol/L) in women
    • BMI (Body Mass Index) >30kg/m² and/or waist:hip ratio >0.9 in men, >0.85 in women
    • Urinary albumin excretion rate ≥20μmg/g or albumin: creatinine ratio ≥30 mg/g.[7]

The American Heart Association reports updated (2013) criteria for diagnosing metabolic syndrome, criteria harmonized among several authoritative sources:[8]

Metabolic syndrome refers to a cluster of risk factors for CVD and type 2 DM. Although several different definitions for metabolic syndrome have been proposed, the International Diabetes Federation, NHLBI, AHA, and others recently proposed a harmonized definition for metabolic syndrome[9] By this definition, metabolic syndrome is diagnosed when ≥3 of the following 5 risk factors are present (most but not all people with DM will be classified as having metabolic syndrome by this definition because they will have at least 2 other factors besides the glucose criterion; many will prefer to separate those with DM into a separate group for risk stratification or treatment purposes):

—Fasting plasma glucose ≥100 mg/dL or undergoing drug treatment for elevated glucose

—HDL cholesterol <40 mg/dL in men or <50 mg/dL in women or undergoing drug treatment for reduced HDL cholesterol.

—Triglycerides ≥150 mg/dL or undergoing drug treatment for elevated triglycerides

—Waist circumference ≥102 cm in men or ≥88 cm in women in the United States.

—BP ≥130 mm Hg systolic or ≥85 mm Hg diastolic or undergoing drug treatment for hypertension or antihypertensive drug treatment in a patient with a history of hypertension.

Risk factors for developing metabolic syndrome

Fetal programming and metabolic syndrome

Refs.[2] [10]

Suboptimal dietary potassium

Study #1

In a cros-sectional study of a representative sample of the U.S. population (>25,000 participants analyzed), Sharma and colleagues[11] concluded:

"Low dietary potassium intake is associated with an increased risk of metabolic syndrome in US adults'."

The study merely identifies an association of low dietary potassium in adults meeting the diagnostic criteria of metabolic syndrome. The association analysis suggested an increased risk of metabolic syndrome of 35% for those with metabolic syndrome consuming 44 mmol/day [1701 mg/day] or less, when compared to those consuming 84 mmol/day [3290 mg/day] or more. The recommended intake of potassium for adult Americans: 120 mmol/day [4700 mg/day]. Accordingly, we do not know what the relative risk of metabolic syndrome when the lower potassium intakes compare with intakes greater than 120 mmol/day, nor from the associational study, whether some type of interventional study that raised potassium intake to >120 mmol/day could prevent or mitigate the metabolic syndrome.

Study #2

In a somewhat similar study, based on the Korean National Health and Nutritional Examination Survey data from 2008 to 2010 (>19,000 participants), Lee and colleagues[12] [13] concluded:

"Our findings suggest that higher potassium intake is significantly associated with lower risk of MS [metabolic syndrome in women of general population and IR [insulin resistance] is thought to be participated in the relationship."

They added:

"These results support the recommendations for higher consumption of potassium rich foods to prevent cardiovascular diseases in another aspect."

Psychological components

An interesting but yet underdeveloped aspect of research on the metabolic syndrome relates to the syndrome's psychological components. 'Cynical hostility' appears to predict the metabolic syndrome, which in turn predicts cardiovascular disease.[14] Worthy of note, in a study, only high hostility and low HDL cholesterol predicted coronary heart disease.[15] At present, there is no agreement on the nature of the relationship between hostility and the metabolic syndrome.

Consequences of the metabolic syndrome

Diabetic complications and cardiovascular diseases

The metabolic syndrome is thus a cluster of risk factors for diabetes complications and cardiovascular diseases. The syndrome includes proinflammatory and prothrombotic features.[7]

Other consequences

The metabolic syndrome could also promote the development of cancer, polycystic ovary syndrome (PCOS), and nonalcoholic fatty liver disease".[16]

Chronic kidney disease

Studies have established an association of metabolic syndrome and new occurrences of chronic kidney disease. Recently investigators have examined whether metabolic syndrome associates with all-cause mortality and end-stage renal disease, in patients with advanced (stages 3 & 4) kidney disease.[17] They concluded:

Presence of MetS [metabolic syndrome] in younger [<50-60 years] stage 3 and stage 4 CKD [chronic kidney disease] patients are associated with all-cause mortality and ESRD [end-stage renal disease]. The associations between individual components of MetS and the composite end-point seem to vary with diabetes and dyslipidemia having pronounced associations.[17]

Others too have found that the metabolic syndrome associates positively with the rate of progression of chronic kidney disease.[18]


A number of components of the metabolic syndrome (MS) are likely to contribute, especially in combination, to cause cancer. While the MS-colon cancer is the most convincing link, other epidemiologic studies investigating the link of MS with other cancers are awaited.[19]


  1. National Library of Medicine. Metabolic Syndrome X. Retrieved on 2007-12-18.
  2. 2.0 2.1 Brenseke B, Prater MR, Bahamonde J, Gutierrez JC. (2013) Current Thoughts on maternal nutrition and fetal programming of the metabolic syndrome. J Pregnancy 2013:368461.
    • Abstract:
    • Chronic diseases such as type 2 diabetes and cardiovascular disease are the leading cause of death and disability worldwide.
    • Although the metabolic syndrome has been defined in various ways, the ultimate importance of recognizing this combination of disorders is that it helps identify individuals at high risk for both type 2 diabetes and cardiovascular disease.
    • Evidence from observational and experimental studies links adverse exposures in early life, particularly relating to nutrition, to chronic disease susceptibility in adulthood.
    • Such studies provide the foundation and framework for the relatively new field of developmental origins of health and disease (DOHaD).
    • Although great strides have been made in identifying the putative concepts and mechanisms relating specific exposures in early life to the risk of developing chronic diseases in adulthood, a complete picture remains obscure.
    • To date [early 2013], the main focus of the field has been on perinatal and specific nutrient however, the current global health crisis of overweight and obesity demands that perinatal and specific nutrient be examined.
    • This paper assembles current thoughts on the concepts and mechanisms behind the DOHaD as they relate to maternal nutrition, and highlights specific contributions made by macro- and micronutrients.
  3. ABC News: The World Is Getting Rounder. Retrieved on 2007-11-17.
  4. What Is Metabolic Syndrome?. Retrieved on 2007-11-17.
  5. Rentoukas E et al. (2012) Connection between telomerase activity in PBMC and markers of inflammationand endothelial dysfunction in patients with metabolic syndrome. PLoS One 7: e35739.
  6. Meigs JB et al. (2007). "Impact of insulin resistance on risk of type 2 diabetes and cardiovascular disease in people with metabolic syndrome". Diabetes Care 30: 1219–25. DOI:10.2337/dc06-2484. PMID 17259468. Research Blogging.
  7. 7.0 7.1 Grundy SM et al. (2004). "Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition". Arterioscler Thromb Vasc Biol 24: e13–8. DOI:10.1161/01.ATV.0000111245.75752.C6. PMID 14766739. Research Blogging.
  8. Heart Disease and Stroke Statistics--2013 Update. Circulation.2013; 127: e6-e245. Published online before print December 12, 2012, doi: 10.1161/CIR.0b013e31828124ad.
  9. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr. (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 120:1640–1645.
  10. Rinaudo, Paolo, and Erica Wang. (2012) Fetal programming and metabolic syndrome. Annual review of physiology. 74:107-130.
    • Abstract:
    • Metabolic syndrome is reaching epidemic proportions, particularly in developing countries.
    • In this review, we explore the concept—based on the developmental-origin-of-health-and-disease hypothesis—that reprogramming during critical times of fetal life can lead to metabolic syndrome in adulthood.
    • Specifically, we summarize the epidemiological evidence linking prenatal stress, manifested by low birth weight, to metabolic syndrome and its individual components.
    • We also review animal studies that suggest potential mechanisms for the long-term effects of fetal reprogramming, including the cellular response to stress and both organ- and hormone-specific alterations induced by stress.
    • Although metabolic syndrome in adulthood is undoubtedly caused by multiple factors, including modifiable behavior, fetal life may provide a critical window in which individuals are predisposed to metabolic syndrome later in life.
  11. Sharma S et al.. (2012) Low dietary potassium intake is associated with an increased risk of metabolic syndrome in US adults. American Society of Nephrology Annual Meeting: Abstract Sessions, Session: Fluid, Electrolyte, and Acid-Base Disorders; Date/Time: Friday, November 2, 2012 10:00 AM - 12:00 PM
    • No peer-reviewed publication available yet. See full-text of Abstract on the Addendum subpage.
  12. Lee H, Jeonghwan LeeJ, ju Heo N, Han JS. (2012) Dietary Potassium Intake and Risk of Metabolic Syndrome Course: American Society of Nephrology Annual Meeting: Abstract Sessions; Session: Fluid, Electrolyte, and Acid-Base Disorders; Date/Time: Friday, November 2, 2012 10:00 AM - 12:00 PM.
    • No peer-reviewed publication available yet. See full-text of Abstract on the Addendum subpage.
  13. Lee H, Lee J, Hwang S-s, Kim S, Chin HJ, Han JS, Heo NJ. (2013) Potassium Intake and the Prevalence of Metabolic Syndrome: The Korean National Health and Nutrition Examination Survey 2008–2010.
    • Adapted from Abstract:
    • [F]ew studies have investigated the effect of potassium intake on metabolic syndrome (MetS).
    • Data was taken from the Korean National Health and Nutritional Examination Survey (2008–2010) using weighted adjustment.
    • Homeostasis model assessment indices were calculated to diagnosis insulin resistance (IR). A total of 16,637 participants (44±0.25 years) were included.
    • Women ingested lower amounts of potassium (2.71±0.02 g/day) than men (3.45±0.03 g/day).
    • For every 1 g/day potassium increase, women with less than the Adequate Intake (4.7 g/day) of potassium had an 11% risk reduction for MetS (P = 0.004) and a 10% risk reduction for IR (P = 0.026).
    • Compared with the reference group (3.5–4.5 g/day), potassium intake was inversely associated with an increased risk of MetS (P = 0.017) and IR (P = 0.021).
    • This relationship was more prominent in postmenopausal women, but not observed among men.
    • Higher potassium intake is significantly associated with a lower MetS prevalence in women, and IR is believed to be connected.
  14. Nelson TL et al. (2004). "The metabolic syndrome mediates the relationship between cynical hostility and cardiovascular disease". Exp Aging Res 30: 163–77. DOI:10.1080/03610730490275148. PMID 15204630. Research Blogging.
  15. Niaura R et al. (2002). "Hostility, the metabolic syndrome, and incident coronary heart disease". Health Psychol 21: 588–93. PMID 12433011.
  16. Biddinger SB, Kahn CR (2006). "From mice to men: insights into the insulin resistance syndromes". Annu. Rev. Physiol 68: 123–58. PMID 16460269.
  17. 17.0 17.1 Navaneedthan SD, Schold JD, Tang AS, Thomas G, Schreiber MJ, Poggio ED, Beddhu S, Nally JV. Abstract: [FR-PO135] Metabolic Syndrome, Kidney Disease Progression and Death. Annual Meeting, American Society of Nephrology. November 2, 2012.
  18. Nitta K. (2012) Abstract: [FR-PO203] Metabolic Syndrome and Risk of Progression of Chronic Kidney Disease: A Single Center Cohort Study. Annual Meeting, American Society of Nephrology. November 2, 2012.
  19. Cowey S, Hardy RW (2006). "The metabolic syndrome: A high-risk state for cancer?". Am J Pathol 169: 1505–22. PMID 17071576.