Metabolic Syndrome

Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. The diagnosis includes measurements of the waist circumference and BP along with serum levels of triglycerides, HDL cholesterol, and fasting glucose. Management consists mostly of lifestyle modifications such as moderate exercise and a balanced diet high in fibers and unsaturated fats and low in sugar.

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Definition and Epidemiology

Definition

Metabolic syndrome is a cluster of biochemical and physiologic abnormalities associated with the development of cardiovascular disease and type 2 diabetes.

Epidemiology

Prevalence:

  • 22%–24% in the United States
  • 32% in Mexican Americans
  • Higher in African American and Mexican American women compared to men of the same ethnicity
  • Increasing with age → up to 44% in people > 60 years of age

Metabolic syndrome doubles the risk for developing cardiovascular disease.

Pathophysiology

With obesity, excess adipose tissue releases the following substances, with considerable effects on the body.

Nonesterified fatty acids (NEFAs)

  • Overload muscle and liver with lipid 
  • ↑ Insulin resistance

Proinflammatory cytokines

  • ↑ CRP levels 
  • ↑ Insulin resistance
  • Atherogenesis

Prothrombotic substances

  • ↑ Plasma plasminogen activator inhibitor (PAI)-1 
  • ↑ Fibrinogen (acute-phase reactant like CRP)

Adiponectin

  • A protein hormone and adipokine
  • Involved in regulating glucose levels 
  • Involved in fatty acid breakdown

Clinical Presentation and Diagnosis

Metabolic syndrome is defined as the presence of ≥ 3 of the following conditions:

  • Central, abdominal, or visceral obesity (characterized by adipose tissue accumulation predominantly around the waist and trunk):
    • Waist circumference: ≥ 102 cm (40 in.) in men
    • Waist circumference: ≥ 88 cm (35 in.) in women
  • Elevated serum triglycerides: ≥ 150 mg/dL 
  • Reduced HDL cholesterol levels: 
    • < 40 mg/dL in men
    • < 50 mg/dL in women
  • Elevated BP: ≥ 130/85 mm Hg (or use of antihypertensives)
  • Elevated fasting glucose: ≥ 100 mg/dL (or use of antihyperglycemic agents)

Management

Lifestyle modifications

Diet:

  • Calorie restriction for weight reduction
  • Carbohydrate restriction: < 55% of daily calorie intake to reduce glucose levels
  • Mediterranean diet: 
    • High in fruits, vegetables, nuts, whole grains, and olive oil 
    • Benefits: weight loss, lowered BP, improved lipid profiles, improved insulin resistance, decreased levels of inflammatory markers 
  • High-fiber diet:
    • About ≥ 30 g/day of fiber 
    • Benefits: weight loss, lowered lipid concentrations, decreased hyperinsulinemia

Exercise:

  • ≥ 30 minutes of moderate exercise 5 days per week 
  • Improves BP
  • Helps revert insulin resistance
  • Promotes weight loss

Pharmacologic and surgical treatment

  • ACE inhibitors and diuretics for hypertension
  • Statins for dyslipidemia
  • Antihyperglycemic agents, including metformin, for type 2 diabetes
  • Bariatric surgery:
    • May be considered for refractory obesity
    • Sleeve gastrectomy
    • Gastric bypass

Clinical Relevance

Metabolic syndrome is associated with several obesity-related disorders, the most important of which include:

  • Type 2 diabetes mellitus: chronic condition characterized by abnormally high levels of blood glucose due to insulin resistance in the body. Patients present with frequent urination, increased thirst, and increased appetite. Management includes lifestyle modifications, drugs for modulation of insulin resistance, and ultimately insulin substitution. Continued hyperglycemia commonly results in angiopathy (often manifesting as foot ulcers and impaired wound healing), neuropathy, retinopathy (vision loss), and nephropathy (CKD).   
  • CKD: gradual loss of kidney function over months to years, most commonly caused by diabetes, hypertension, glomerulonephritis, and polycystic kidney disease. The majority of patients develop only nonspecific symptoms at a late stage, including confusion and tiredness, loss of appetite, and leg swelling. Management includes ACE inhibitors and adequate blood glucose and BP control. Ultimately, dialysis or kidney transplantation is required. Metabolic syndrome increases the risk of CKD. 
  • Polycystic ovary syndrome (PCOS):  condition in which the ovaries produce an abnormal amount of androgens. Patients present with irregular menstrual cycles, infertility, acne and hirsutism, and metabolic syndrome. Diagnosis is based on detection of anovulation, high androgen levels, and multiple ovarian cysts. Management includes lifestyle modifications and antiandrogenic drugs.
  • Obstructive sleep apnea (OSA): sleep-related breathing condition characterized by recurrent episodes of complete or partial obstruction of the upper airway. Patients present with reduced or partly absent breathing during sleep that is often associated with loud snoring, headaches, and daytime sleepiness. Management includes weight loss for obese patients as well as continuous positive airway pressure (CPAP) and mandibular advancement devices.
  • Gout: type of inflammatory arthritis that causes painful attacks of joint pain, most commonly at the base of the big toe. Chronic hyperuricemia leads to the deposition of uric acid crystals in joints and tendons. Prevention includes avoiding alcohol, fructose, and organ meats and seafood high in purine. Acute attacks are treated with NSAIDs, colchicine, and glucocorticoids.

References

  1. Mayans, L. (2015). Metabolic syndrome: insulin resistance and prediabetes. FP Essentials 435:11–16. Retrieved April 15, 2021, from https://pubmed.ncbi.nlm.nih.gov/26280340/
  2. Meigs, J. (2021). Metabolic syndrome (insulin resistance syndrome or syndrome X), UpToDate. Retrieved April 13, 2021, from https://www.uptodate.com/contents/metabolic-syndrome-insulin-resistance-syndrome-or-syndrome-x
  3. Grundy, S.M., Brewer, H.B., Jr., Cleeman, J.I., et al. (2005). Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112:2735–2752. Retrieved April 15, 2021, from https://www.ahajournals.org/doi/10.1161/01.CIR.0000111245.75752.C6
  4. Alberti, K. G. M. M., et al. (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. Retrieved April 15, 2021, from doi:10.1161/CIRCULATIONAHA.109.192644.https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.109.192644
  5. Ford, E.S., Giles, W.H., Dietz, W.H. (2002). Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 287:356–359. doi:10.1001/jama.287.3.356 
  6. Moore, J.X., Chaudhary, N., Akinyemiju, T. (2017). Metabolic syndrome prevalence by race/ethnicity and sex in the United States, National Health and Nutrition Examination Survey, 1988–2012. Preventing chronic disease. Retrieved April 15, 2021, from https://www.cdc.gov/pcd/issues/2017/16_0287.htm
  7. Lakka, H.M., et al. (2002). The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288:2709–2716. doi:10.1001/jama.288.21.2709
  8. Kurella, M., et al. (2005). Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults. Journal of the American Society of Nephrology 16:2134–2140. https://pubmed.ncbi.nlm.nih.gov/15901764/

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