metabolic syndrome X; obesity syndrome x; insulin-resistance syndrome; dysmetabolic syndrome

Introduction

Characterizes individuals at risk for coronary artery disease.

Etiology

• excess calorie intake
• inactivity
• linked to work stress
• financial worry, intimate partner violence, neighborhood poverty, depression
• intestinal flora may play a role
• chemotherapy, especially combination chemotherapy

Epidemiology

• overall prevalence 24%
• prevalence of 44% age 60-70
• Mexican-Americans with highest prevalence of 32%
• male:female ratio 1 for whites, but < 1 for African-Americans & Mexican-Americans

Pathology

• inflammation may play a role in cardiovascular risk & risk of frailty
• syndrome also occurs in primates

Genetics

• implicated genes: INPPL1, ENPP1

Clinical manifestations

• abdominal obesity
  • elevated waist circumference
    • > 102 cm or 40 " in men, > 88 cm or 35 " in women
• dyslipidemia (see Laboratory)
• elevated blood pressure
  • blood pressure* > 130/85 mm Hg or use of anti-hypertensive agent
  • systolic BP > 130 mm Hg or diastolic BP > 85 mm Hg
• insulin resistance
• waist circumference*
  • > 102 cm (40 inches) in men; > 88 cm (35 inches) in women
  • in Asian-Americans, > 89 cm (35 inches) in men or > 79 cm (31 inches) in women
• erectile dysfunction is common

* defining characteristics; 3 or 4 makes diagnosis (also see Laboratory)

Laboratory

• serum triglycerides* > 150 mg/dL or drug therapy targeting elevated serum triglycerides
• HDL cholesterol* < 40 mg/dL (men), < 50 mg/dL (women) or drug therapy targeting low HDL cholesterol
• fasting serum glucose* > 100 mg/dL or use of hypoglycemic agent
• elevated serum C-reactive protein is an inflammatory marker of metabolic syndrome
• elevated 11-beta-hydroxysteroid dehydrogenase-1 in adipose tissue
• see ARUP consult

* defining characteristics; 3 or 4 makes diagnosis (also see Clinical manifestations)

Diagnostic procedures

• lower scores on standardized tests of arithmetic & spelling (adolescents)

Radiology

• magnetic resonance imaging of brain (adolescents)
  • reduced hippocampal volume
  • increased cerebrospinal fluid volume

Complications

• increased risk of cardiovascular disease
  • risk of myocardial infarction similar to that conferred by diabetes mellitus type-2 alone
  • stroke
  • recovery from metabolic syndrome associated with reduced risk for major cardiovascular events
• increased risk of diabetes mellitus type-2
• increased risk of frailty

• disease interaction(s) of metabolic syndrome with frailty

Management

• intensified life-style management
  • diet
    • multicomponent American Heart Association (AHA) diet
    • increasing fiber alone of benefit
  • exercise
    • moderate pace walking for 1 hour once or twice a week may be inadequate in some patients
    • a personalized exercise program incorporating an activity tracker may help reduce the severity of metabolic syndrome
    • see exercise
• pharmaceutical agents
  • consider statin for hyperlipidemia
    • cardiovascular risk further reduced with addition of fenofibrate to statin (risk of rhabdomyolysis may be increased)
  • consider ACE inhibitor for hypertension
  • consider metformin or acarbose for hyperglycemia
  • aspirin 81 mg QD if 10 year cardiovascular risk > 10%
• treatment of obstructive sleep apnea with CPAP may improve some components of metabolic syndrome, especially hypertension
• gastric bypass
• sirtuins, because of their induction by life-prolonging calorie restriction, may serve as potential therapeutic targets for metabolic syndrome

Comparative biology

• relatively large numbers of Firmicutes & small numbers of Bacteroidetes in the rats' intestine leads to glucose intolerance & obesity
• + Firmicutes/- Bacteroidetes is associated with high amounts of acetate in the gut & this is increased by high-fat diet
• acetate is absorbed from the gut into the circulation & crosses the blood-brain barrier into the brain
• within the brain, acetate stimulates the parasympathetic nervous system to increase pancreatic beta-cell production of insulin in response to gluxose & increases production of ghrelin in the stomach
• elimination of gut bacteria with antibiotics, vagotomy or administration of atropine revereses effect

More general terms

• chronic metabolic disease
• syndrome

Additional terms

• 11-beta hydroxysteroid dehydrogenase-1 (corticosteroid 11-beta-dehydrogenase isozyme 1, 11-DH, 11-beta-HSD1, HSD11B1, HSD11, HSD11L)
• diabetes mellitus
• hypertension (HTN, high blood pressure, HBP)
• hypertriglyceridemia
• obesity

Database

• OMIM: https://mirror.omim.org/entry/125853