Key Facts

Metabolic syndrome is not a single disease but a constellation of interrelated metabolic abnormalities that significantly increase the risk of cardiovascular disease and type 2 diabetes. Identification allows targeted risk factor management.

Epidemiology

• Prevalence: approximately 30% of UK adults
• Increases with age: ~40% in over-60s
• Higher prevalence in South Asian populations (lower waist circumference thresholds apply)
• Strongly linked to the obesity epidemic

Aetiology

• Central (visceral) obesity is the primary driver
• Sedentary lifestyle and excess caloric intake
• Genetic predisposition (polygenic)
• In-utero programming (low birth weight → adult metabolic syndrome)

Pathophysiology

• Visceral adipose tissue is metabolically active → releases free fatty acids, inflammatory cytokines (TNF-alpha, IL-6), and adipokines
• Insulin resistance: impaired glucose uptake in muscle and liver → compensatory hyperinsulinaemia
• Hyperinsulinaemia promotes hepatic VLDL synthesis → raised triglycerides, low HDL
• Insulin resistance contributes to endothelial dysfunction and hypertension
• Chronic low-grade inflammation and prothrombotic state
• Ectopic fat deposition (liver, pancreas, muscle) perpetuates insulin resistance

Central Obesity

• Increased waist circumference: ≥94cm (men), ≥80cm (women) for Europid populations
• Visceral/abdominal adiposity

Metabolic Features

• Raised triglycerides (≥1.7 mmol/L)
• Low HDL cholesterol (<1.03 mmol/L men, <1.29 mmol/L women)
• Raised blood pressure (≥130/85 mmHg or on treatment)
• Raised fasting glucose (≥5.6 mmol/L or diagnosed type 2 diabetes)

Associated Conditions

• Acanthosis nigricans (dark, velvety skin in flexures – marker of insulin resistance)
• Non-alcoholic fatty liver disease (up to 90% of patients with metabolic syndrome)
• Skin tags
• Gout/hyperuricaemia

Red Flags

• Symptoms of cardiovascular disease (chest pain, TIA/stroke symptoms)
• Fasting glucose >7.0 mmol/L or HbA1c ≥48 mmol/mol → screen for diabetes
• Signs of obstructive sleep apnoea (excessive daytime somnolence)

Bedside

• Waist circumference measurement (at midpoint between lower rib and iliac crest)
• BMI
• Blood pressure: on two or more occasions

Bloods

• Fasting glucose and/or HbA1c: screen for diabetes/pre-diabetes
• Fasting lipid profile: total cholesterol, HDL, LDL (calculated), triglycerides
• LFTs: screen for NAFLD (ALT often elevated)
• FBC, U&Es: baseline
• Uric acid: associated hyperuricaemia
• Fasting insulin: not routinely measured (HOMA-IR can be calculated for research)

Imaging

• Liver ultrasound: if suspected NAFLD (fatty liver)
• FibroScan: if NAFLD confirmed, assess fibrosis stage

Special Tests

• OGTT: if fasting glucose 6.1-6.9 mmol/L (impaired fasting glucose)
• QRISK3: 10-year cardiovascular risk assessment
• Sleep study: if clinical suspicion of OSA

Non-pharmacological

• Lifestyle modification is the cornerstone of treatment
• Weight loss of 5-10% improves all metabolic parameters
• Dietary modification: Mediterranean diet, reduced refined carbohydrates and sugars, increased fibre
• Exercise: 150 minutes/week moderate-intensity aerobic exercise + resistance training
• Smoking cessation
• Limit alcohol intake

Pharmacological

Treat each component per individual NICE guidelines:

• Hypertension: per NICE NG136
  • ACE inhibitor/ARB first-line (especially if diabetic)
  • Target BP <140/90 (or <130/80 if diabetic)
• Dyslipidaemia: per NICE CG181
  • Atorvastatin 20mg OD if QRISK3 ≥10%
  • Atorvastatin 80mg if established CVD
• Hyperglycaemia/Type 2 diabetes: per NICE NG28
  • Metformin 500mg-2g daily (first-line, also addresses insulin resistance)
  • SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin) – cardiovascular and renal benefits
  • GLP-1 receptor agonists (e.g., semaglutide, liraglutide) – weight loss + CV benefit
• Obesity: per NICE CG189
  • Consider orlistat 120mg TDS if BMI ≥30 (or ≥28 with comorbidities)
  • Semaglutide 2.4mg SC weekly (Wegovy) for weight management
  • Bariatric surgery if BMI ≥40 (or ≥35 with comorbidities)

Referral Criteria

• BMI ≥40 (or ≥35 with comorbidities) → bariatric surgery assessment
• Resistant hypertension → secondary care
• NAFLD with significant fibrosis → hepatology
• Suspected secondary cause of obesity (Cushing, hypothyroidism)

• Metabolic syndrome increases risk of type 2 diabetes 5-fold and cardiovascular events 2-3 fold
• 5-10% weight loss can resolve metabolic syndrome in many patients
• NAFLD progresses to NASH in ~20%, cirrhosis in ~5%
• Bariatric surgery can resolve metabolic syndrome in >80% of patients
• Without intervention, progressive worsening of all components is expected
• Addressing individual components significantly reduces absolute cardiovascular risk

IDF Diagnostic Criteria (2005)

Central obesity (waist circumference ≥94cm men, ≥80cm women for Europid) PLUS ≥2 of:

Ethnicity-Specific Waist Circumference Thresholds