Metabolic Syndrome
Summary
Metabolic Syndrome is not a single disease but a cluster of metabolic abnormalities that significantly increase the risk of Cardiovascular Disease (CVD) and Type 2 Diabetes Mellitus (T2DM). The core components are Central Obesity, Dyslipidaemia, Hypertension, and Hyperglycaemia. The unifying underlying mechanism is Insulin Resistance, driven primarily by visceral adiposity. Patients with Metabolic Syndrome have a 2-fold risk of CVD and a 5-fold risk of developing Diabetes over 5-10 years. [1,2]
Key Facts
- Insulin Resistance (IR): Cells stop responding to insulin -> Pancreas works harder (Hyperinsulinaemia) -> Eventually fails (Diabetes). IR also causes endothelium dysfunction (HTN) and alters lipid metabolism.
- Visceral Fat: The "Beer Belly". It is not just inert storage; it is a metabolically active organ secreting inflammatory cytokines (TNF-alpha, IL-6) and Non-Esterified Fatty Acids (NEFAs) which poison the liver and muscles.
- NAFLD: Non-Alcoholic Fatty Liver Disease is the hepatic manifestation of metabolic syndrome. It is becoming the leading cause of liver transplant.
Clinical Pearls
Waist Circumference: The single most useful physical sign. BMI can be misleading (muscular men). A large waist (>94cm in European men, >80cm in women) correlates directly with visceral fat and insulin resistance.
Acanthosis Nigricans: Look for dark, velvety patches in the axilla, neck, and groins. This is a pathognomonic skin sign of profound insulin resistance (high insulin stimulates melanocytes).
Polycystic Ovaries (PCOS): Often considered the ovarian manifestation of metabolic syndrome. Always screen women with PCOS for metabolic syndrome.
Demographics
- Prevalence: 20-30% of the adult population in developed countries.
- Age: Risk increases with age, but increasingly common in children/adolescents.
- Ethnicity: Higher risk in South Asians (who develop metabolic complications at lower BMIs).
Definition (IDF 2006 Consensus)
Central Obesity (Waist >94cm M, >80cm F - ethnicity specific) PLUS any 2 of:
- Triglycerides: > 1.7 mmol/L (or on treatment).
- HDL Cholesterol: < 1.03 M, < 1.29 F (or on treatment).
- Blood Pressure: > 130/85 mmHg (or on treatment).
- Fasting Glucose: > 5.6 mmol/L (or diagnosed T2DM).
The Vicious Cycle
- Visceral Adiposity: Excess calories stored as deep abdominal fat.
- Lipotoxicity: Fat cells release free fatty acids (FFAs) into the portal vein.
- Hepatic IR: Assessing FFAs, the liver makes more Glucose (Gluconeogenesis) and VLDL (Triglycerides).
- Peripheral IR: FFAs block insulin signaling in muscle (less glucose uptake).
- Hyperinsulinaemia: Pancreas compensates. High insulin causes Sodium retention (Hypertension) and reduced SHBG.
- Inflammation: Adipocytes release IL-6/TNF-a -> Pro-thrombotic, Pro-inflammatory state.
Symptoms
Signs
- Waist Circumference: Measure at midpoint between iliac crest and lowest rib.
- BMI: Calculate.
- Blood Pressure.
- Liver: Hepatomegaly (Fatty infiltration).
Biochemistry
- Lipid Profile: Hallmark is High Triglycerides + Low HDL. (LDL often normal but dense/atherogenic).
- Fasting Glucose/HbA1c: Screen for Pre-diabetes/Diabetes.
- Liver Function Tests: Mildly elevated ALT/GGT is classic for fatty liver.
- Uric Acid: Often elevated (Gout risk).
Imaging
- Liver Ultrasound: "Bright liver" (Fatty change).
Management Algorithm
METABOLIC SYNDROME
↓
LIFESTYLE MODIFICATION
(Weight Loss 5-10% is Primary Goal)
- Diet: Mediterranean / Low Carb
- Exercise: 150 mins/week moderate
↓
┌─────────────┼─────────────┐
GLUCOSE LIPIDS PRESSURE
↓ ↓ ↓
Metformin Statins ACEi / ARB
(If Pre-DM) (Target risk) (Target less than 130/80)
↓
NEW THERAPIES
- GLP-1 Agonists (Semaglutide)
- SGLT-2 Inhibitors
(Treat both weight and glucose)
1. Lifestyle (The Cornerstone)
- Weight Loss: Losing 5-10% of body weight improves all 5 components of the syndrome. It is more effective than any single drug.
- Diet: Mediterranean diet (proven to reduce CV risk). Reduce refined carbohydrates/sugar.
- Exercise: Improves insulin sensitivity even without weight loss.
2. Pharmacotherapy
- Statins: Primary prevention of CVD. (Atorvastatin 20mg).
- Antihypertensives: ACE Inhibitors (Ramipril) are first line as they are renal protective/metabolically neutral.
- Metformin: Considered in pre-diabetes with high BMI.
- GLP-1 Analogues (e.g. Semaglutide/Wegovy): Powerful tool for weight loss and glycaemic control. Now recommended for obesity with complications.
3. Bariatric Surgery
- Considered for BMI >35 with comorbidities. Can induce remission of T2DM in up to 80%.
- Cardiovascular: Myocardial Infarction, Stroke, Peripheral Vascular Disease.
- Hepatic: NASH (Non-Alcoholic Steatohepatitis) -> Cirrhosis -> Hepatocellular Carcinoma.
- Reproductive: PCOS, Erectile Dysfunction.
- Renal: Microalbuminuria, CKD.
- Reversible with weight loss.
- High lifetime risk of frank Diabetes without intervention.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| CVD Prevention | ESC / EAS (2021) | Aggressive lipid and BP targets. Lifestyle first. |
| Obesity | NICE | Referral criteria for bariatric surgery. Use of GLP-1s. |
Landmark Trials
1. Diabetes Prevention Program (DPP)
- Comparison: Lifestyle vs Metformin vs Placebo in Pre-diabetes.
- Result: Lifestyle intervention reduced incidence of Diabetes by 58%. Metformin reduced it by 31%.
- Conclusion: Lifestyle is superior to drugs.
What is Metabolic Syndrome?
It is a "perfect storm" of health problems—a large waistline, high blood pressure, high cholesterol, and high blood sugar—that occur together.
Why do I have it?
It is usually linked to being overweight (especially around the tummy) and inactivity, which makes your body resistant to insulin (the hormone that controls sugar). Genetics also play a part.
Is it dangerous?
Yes. Having this combination makes you 5 times more likely to get Diabetes and twice as likely to have a heart attack or stroke compared to someone without it.
Can I fix it?
Yes! The good news is that because all these problems are linked to weight, losing just 5-10% of your body weight can fix all of them at once. It is the most powerful medicine you can take.
Primary Sources
- Alberti KG, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force.... Circulation. 2009.
- Knowler WC, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002. (DPP Study).
- Eckel RH, et al. The metabolic syndrome. Lancet. 2005.
Common Exam Questions
- Define: "Criteria for Metabolic Syndrome?"
- Answer: Central obesity + 2 of (High TG, Low HDL, HTN, High Glue).
- Pathology: "Underlying mechanism?"
- Answer: Insulin Resistance.
- Dermatology: "Skin sign of insulin resistance?"
- Answer: Acanthosis Nigricans.
- Treatment: "Most effective intervention?"
- Answer: Lifestyle / Weight loss (DPP study).
Viva Points
- Ethnicity thresholds: Why lower for Asians? Asians have higher visceral fat for the same BMI ("Thin-fat phenotype"), leading to insulin resistance at lower waist circumferences (>90cm M, >80cm F).
- NAFLD: The hepatic manifestation. If you see high ALT in an obese patient, think Fatty Liver.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.