Metabolic syndrome natural history, complications and prognosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Priyamvada Singh, M.B.B.S. [2]; Raviteja Guddeti, M.B.B.S. [3]; Aarti Narayan, M.B.B.S [4]
Overview
Metabolic syndrome occurs in the presence of insulin resistance and accompanying obesity. It increases the risk for coronary heart disease, type II diabetes, fatty liver, stroke and some cancers. It may manifest as hypertension, hyperglycemia, hypertriglyceridemia, reduced high density lipoprotein cholesterol and abdominal obesity. 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.
Natural History
If left untreated, consistently high levels of insulin in metabolic syndrome usually leads to type 2 diabetes. Insulin resistance is also associated with many changes in the body prior to its manifesting as disease including chronic inflammation and damage to arterial walls, decreased excretion by the kidneys, and coagulopathies.
Complications
The complications found associated with metabolic syndrome are:
- Type II diabetes mellitus: The Framingham Heart Study cohort found that metabolic syndrome is a strong predictor of new-onset diabetes in both men and women. It was also shown that obese people with metabolic syndrome have a 10-fold higher risk for developing new diabetes when compared to obese people without metabolic syndrome. Prospective studies have shown that hyper-insulinemia, body size and lipid factors are strongly associated with the development of diabetes in patients with metabolic syndrome. [1][2][3][4][5][6]
- Cardiovascular complications: The Framingham Heart Study showed that obese people with metabolic syndrome have a 2-fold higher risk for cardiovascular disease (CVD) when compared to obese people without metabolic syndrome. The increased risk for CVD can be due to either risk factor clustering or insulin resistance and obesity. Obese patients with insulin resistance have the highest risk for developing CVD.[4][5][6][7]
- Coronary heart disease
- Atrial fibrillation
- Heart failure
- Aortic stenosis
- Stroke: The Northern Manhattan study in 3298 stroke free subjects showed that metabolic syndrome increases the risk for ischemic stroke. The risk is greater in women compared to men and Hispanics compared to Caucasians and African-Americans.[8] A similar study in Japan showed the increased risk of ischemic stroke in women with metabolic syndrome.[9][10]
- Chronic kidney disease: Many prospective cross-sectional studies have shown that metabolic syndrome is strongly associated with the development of chronic kidney disease (CKD) over the years. It was also shown that the more components of metabolic syndrome the more the risk for developing CKD.[11][12][13][14]
- Nonalcoholic fatty liver disease, cirrhosis: A fatty liver is insulin resistant and is directly correlated to other components of metabolic syndrome independent of obesity. Insulin resistance, oxidative stress, apoptosis and adipokines are thought to be involved in the pathogenesis of fatty liver disease in metabolic syndrome. The risk of nonalcoholic fatty liver and liver fibrosis increases with presence of elevated waist/hip ratio, impaired glucose tolerance, hypertension, and dyslipidemia. The risk of cardiovascular diseases is very high in patients with metabolic syndrome associated with nonalcoholic fatty liver disease. These patients are also more likely to have excess intra-abdominal fat and inflammatory changes in adipose tissue.[15][16][17][18][19][16][17][15][18]
- Obstructive sleep apnea: Sleep apnea is seen frequently in patients with metabolic syndrome. In a study conducted in 228 patients it was shown that patients with obstructive sleep apnea (OSA) had a higher prevalence of metabolic syndrome compared with patients without OSA. [20][21]
- Breast cancer: Adipokines in metabolic syndrome are known to alter plasminogen activator inhibitor - 1 (PAI-1) expression to promote angiogenesis, tumor cell migration and pro-coagulant micro-particle formation from endothelial cells. The endothelial cells in turn generate thrombin and further propagates PAI-1 synthesis. Elevated levels of PAI-1 have been shown to be associated with poor prognosis in breast cancer. All these factors lead to the risk of developing chemotherapy-resistant breast cancer. Moreover hyper-insulinemia with insulin resistance is known to be associated with proliferative tissue abnormalities through IGF-1 receptor. [22][23] [24]
- Cancers of the liver, colon, gallbladder, kidney, and prostate gland: Obesity is known to be consistently associated with an increased risk for developing cancers of the liver, colon, gallbladder, kidney and prostate gland. Obesity, insulin resistance and metabolic syndrome are associated with elevated levels of inflammatory markers like leptin, interleukin-6 and TNF which are known to enhance tumor growth.[25][26]
- Polycystic ovary syndrome: Insulin resistance and visceral obesity are two important features of polycystic ovarian syndrom (PCOS) similar to metabolic syndrome. Metabolic syndrome is much more common in women with polycystic ovarian syndrom (PCOS) that in women without polycystic ovarian syndrom (PCOS). In the USA almost 50% of PCOS patients have associated metabolic syndrome. [27][28]
- Hyperuricemia and gout: Data from the Third National Health and Nutrition Examination Survey (1988-1994) in 8,807 participants aged ≥20 years showed that the prevalence of metabolic syndrome is remarkably high among individuals with gout.[29]
- Psoriasis: Multiple epidemiologic studies have shown that patients with psoriasis have a higher prevalence of metabolic syndrome. [30][31][32][33]
- Accelerated cognitive decline in the elderly: Studies have shown that compared to elderly people without metabolic syndrome, those with metabolic syndrome have a higher prevalence of cognitive impairment. [34] [35]
Supportive Trial Data
- SOURCE and YEAR: The American Journal of Cardiology
- OBJECTIVE: Estimate the long-term relative risk of major coronary events (MCEs) associated with the metabolic syndrome
- METHOD: Post hoc determination of placebo data from the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) used to estimate the long-term relative risk of major coronary events (MCEs) associated with the metabolic syndrome.
- RESULTS: In the Scandinavian Simvastatin Survival Study and AFCAPS/TexCAPS, respectively, placebo-treated patients with the metabolic syndrome were-
- 1.5 (95% confidence interval 1.2 to 1.8) times more likely to have MCEs than those without it in 4S
- 1.4 (95% confidence interval 1.04 to 1.9) times more likely to have MCEs than those without it in 4S
- CONCLUSION: The following risks factors increased the relative risk for MACE
- Low high-density lipoprotein levels were associated with elevated risk of MCEs in both studies
- High triglycerides in the Scandinavian Simvastatin Survival Study
- Elevated blood pressure and obesity in AFCAPS/TexCAPS were associated with a significantly increased relative risk.
Prognosis
Prognosis is generally good with appropriate treatment and life style modifications.
References
- ↑ Hanson RL, Imperatore G, Bennett PH, Knowler WC (2002). "Components of the "metabolic syndrome" and incidence of type 2 diabetes". Diabetes. 51 (10): 3120–7. PMID 12351457. Unknown parameter
|month=ignored (help) - ↑ Resnick HE, Jones K, Ruotolo G; et al. (2003). "Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease in nondiabetic american indians: the Strong Heart Study". Diabetes Care. 26 (3): 861–7. PMID 12610050. Unknown parameter
|month=ignored (help) - ↑ Klein BE, Klein R, Lee KE (2002). "Components of the metabolic syndrome and risk of cardiovascular disease and diabetes in Beaver Dam". Diabetes Care. 25 (10): 1790–4. PMID 12351479. Unknown parameter
|month=ignored (help) - ↑ 4.0 4.1 Sattar N, Gaw A, Scherbakova O; et al. (2003). "Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study". Circulation. 108 (4): 414–9. doi:10.1161/01.CIR.0000080897.52664.94. PMID 12860911. Unknown parameter
|month=ignored (help) - ↑ 5.0 5.1 Sattar N, McConnachie A, Shaper AG; et al. (2008). "Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcome data from two prospective studies". Lancet. 371 (9628): 1927–35. doi:10.1016/S0140-6736(08)60602-9. PMID 18501419. Unknown parameter
|month=ignored (help) - ↑ 6.0 6.1 Ford ES (2005). "Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence". Diabetes Care. 28 (7): 1769–78. PMID 15983333. Unknown parameter
|month=ignored (help) - ↑ Galassi A, Reynolds K, He J (2006). "Metabolic syndrome and risk of cardiovascular disease: a meta-analysis". The American Journal of Medicine. 119 (10): 812–9. doi:10.1016/j.amjmed.2006.02.031. PMID 17000207. Unknown parameter
|month=ignored (help) - ↑ Boden-Albala B, Sacco RL, Lee HS; et al. (2008). "Metabolic syndrome and ischemic stroke risk: Northern Manhattan Study". Stroke; a Journal of Cerebral Circulation. 39 (1): 30–5. doi:10.1161/STROKEAHA.107.496588. PMC 2677015. PMID 18063821. Unknown parameter
|month=ignored (help) - ↑ Takahashi K, Bokura H, Kobayashi S, Iijima K, Nagai A, Yamaguchi S (2007). "Metabolic syndrome increases the risk of ischemic stroke in women". Internal Medicine (Tokyo, Japan). 46 (10): 643–8. PMID 17527036.
- ↑ Air EL, Kissela BM (2007). "Diabetes, the metabolic syndrome, and ischemic stroke: epidemiology and possible mechanisms". Diabetes Care. 30 (12): 3131–40. doi:10.2337/dc06-1537. PMID 17848611.
- ↑ Kurella M, Lo JC, Chertow GM (2005). "Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults". Journal of the American Society of Nephrology : JASN. 16 (7): 2134–40. doi:10.1681/ASN.2005010106. PMID 15901764. Unknown parameter
|month=ignored (help) - ↑ Peralta CA, Kurella M, Lo JC, Chertow GM (2006). "The metabolic syndrome and chronic kidney disease". Current Opinion in Nephrology and Hypertension. 15 (4): 361–5. doi:10.1097/01.mnh.0000232875.27846.7e. PMID 16775449. Unknown parameter
|month=ignored (help) - ↑ Zhang L, Zuo L, Wang F; et al. (2007). "Metabolic syndrome and chronic kidney disease in a Chinese population aged 40 years and older". Mayo Clinic Proceedings. Mayo Clinic. 82 (7): 822–7. doi:10.4065/82.7.822. PMID 17605962. Unknown parameter
|month=ignored (help) - ↑ Chen J, Muntner P, Hamm LL; et al. (2004). "The metabolic syndrome and chronic kidney disease in U.S. adults". Annals of Internal Medicine. 140 (3): 167–74. PMID 14757614. Unknown parameter
|month=ignored (help) - ↑ 15.0 15.1 Marceau P, Biron S, Hould FS; et al. (1999). "Liver pathology and the metabolic syndrome X in severe obesity". The Journal of Clinical Endocrinology and Metabolism. 84 (5): 1513–7. PMID 10323371. Unknown parameter
|month=ignored (help) - ↑ 16.0 16.1 Kotronen A, Yki-Järvinen H (2008). "Fatty liver: a novel component of the metabolic syndrome". Arterioscler Thromb Vasc Biol. 28 (1): 27–38. doi:10.1161/ATVBAHA.107.147538. PMID 17690317.
- ↑ 17.0 17.1 Kim CH, Younossi ZM (2008). "Nonalcoholic fatty liver disease: a manifestation of the metabolic syndrome". Cleveland Clinic Journal of Medicine. 75 (10): 721–8. PMID 18939388. Unknown parameter
|month=ignored (help) - ↑ 18.0 18.1 Hamaguchi M, Kojima T, Takeda N; et al. (2005). "The metabolic syndrome as a predictor of nonalcoholic fatty liver disease". Annals of Internal Medicine. 143 (10): 722–8. PMID 16287793. Unknown parameter
|month=ignored (help) - ↑ Hanley AJ, Williams K, Festa A, Wagenknecht LE, D'Agostino RB, Haffner SM (2005). "Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study". Diabetes. 54 (11): 3140–7. PMID 16249437. Unknown parameter
|month=ignored (help) - ↑ Vgontzas AN, Bixler EO, Chrousos GP (2005). "Sleep apnea is a manifestation of the metabolic syndrome". Sleep Medicine Reviews. 9 (3): 211–24. doi:10.1016/j.smrv.2005.01.006. PMID 15893251. Unknown parameter
|month=ignored (help) - ↑ Parish JM, Adam T, Facchiano L (2007). "Relationship of metabolic syndrome and obstructive sleep apnea". Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine. 3 (5): 467–72. PMC 1978322. PMID 17803009. Unknown parameter
|month=ignored (help) - ↑ Sinagra D, Amato C, Scarpilta AM; et al. (2002). "Metabolic syndrome and breast cancer risk". European Review for Medical and Pharmacological Sciences. 6 (2–3): 55–9. PMID 12708611.
- ↑ Buttros DB, Nahas EA, Vespoli HD, Uemura G, de Almeida BD, Nahas-Neto J (2012). "Risk of metabolic syndrome in postmenopausal breast cancer survivors". Menopause (New York, N.Y.). doi:10.1097/gme.0b013e318272bd4a. PMID 23149866. Unknown parameter
|month=ignored (help) - ↑ Beaulieu LM, Whitley BR, Wiesner TF, Rehault SM, Palmieri D, Elkahloun AG; et al. (2007). "Breast cancer and metabolic syndrome linked through the plasminogen activator inhibitor-1 cycle". Bioessays. 29 (10): 1029–38. doi:10.1002/bies.20640. PMID 17876797.
- ↑ Hsing AW, Sakoda LC, Chua S (2007). "Obesity, metabolic syndrome, and prostate cancer". Am J Clin Nutr. 86 (3): s843–57. PMID 18265478.
- ↑ Welzel TM, Graubard BI, Zeuzem S, El-Serag HB, Davila JA, McGlynn KA (2011). "Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-Medicare database". Hepatology (Baltimore, Md.). 54 (2): 463–71. doi:10.1002/hep.24397. PMID 21538440. Unknown parameter
|month=ignored (help) - ↑ Carmina E (2006). "Metabolic syndrome in polycystic ovary syndrome". Minerva Ginecologica. 58 (2): 109–14. PMID 16582867. Unknown parameter
|month=ignored (help) - ↑ Essah PA, Wickham EP, Nestler JE (2007). "The metabolic syndrome in polycystic ovary syndrome". Clinical Obstetrics and Gynecology. 50 (1): 205–25. doi:10.1097/GRF.0b013e31802f3547. PMID 17304037. Unknown parameter
|month=ignored (help) - ↑ Choi HK, Ford ES, Li C, Curhan G (2007). "Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey". Arthritis and Rheumatism. 57 (1): 109–15. doi:10.1002/art.22466. PMID 17266099. Unknown parameter
|month=ignored (help) - ↑ Gottlieb AB, Dann F, Menter A (2008). "Psoriasis and the metabolic syndrome". J Drugs Dermatol. 7 (6): 563–72. PMID 18561588.
- ↑ Gelfand JM, Yeung H (2012). "Metabolic syndrome in patients with psoriatic disease". The Journal of Rheumatology. Supplement. 89: 24–8. doi:10.3899/jrheum.120237. PMID 22751586. Unknown parameter
|month=ignored (help) - ↑ Saraceno R, Ruzzetti M, De Martino MU; et al. (2008). "Does metabolic syndrome influence psoriasis?". European Review for Medical and Pharmacological Sciences. 12 (5): 339–41. PMID 19024221.
- ↑ Love TJ, Qureshi AA, Karlson EW, Gelfand JM, Choi HK (2011). "Prevalence of the metabolic syndrome in psoriasis: results from the National Health and Nutrition Examination Survey, 2003-2006". Archives of Dermatology. 147 (4): 419–24. doi:10.1001/archdermatol.2010.370. PMC 3075375. PMID 21173301. Unknown parameter
|month=ignored (help) - ↑ Panza F, Frisardi V, Capurso C; et al. (2010). "Metabolic syndrome and cognitive impairment: current epidemiology and possible underlying mechanisms". Journal of Alzheimer's Disease : JAD. 21 (3): 691–724. doi:10.3233/JAD-2010-091669. PMID 20571214.
- ↑ Yaffe K (2007). "Metabolic syndrome and cognitive decline". Curr Alzheimer Res. 4 (2): 123–6. PMID 17430234.
- ↑ Girman CJ, Rhodes T, Mercuri M, Pyörälä K, Kjekshus J, Pedersen TR; et al. (2004). "The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)". Am J Cardiol. 93 (2): 136–41. PMID 14715336.