Lecture 4 - Metabolic Syndrome: Definitions and Causes Flashcards
Core components of metabolic syndrome
1) Obesity
2) Insulin resistance/glucose intolerance
3) Hypertension
4) Dyslipidaemia
WHO definition of metabolic syndrome
Mandatory component: High insulin, high fasting blood glucose levels, high post-meal blood glucose levels
At least 2 of the following:
- Abdominal obesity (BMI over 30kg/m2, waist/hip over 0.9)
- Triglyceride level over 1.7mmol/L
- HDL cholesterol under 0.9mmol/L
- Blood pressure of 140/90 or above
NCEP - ATP III definition of metabolic syndrome
Three or more of the following:
1) Central obesity (waist larger than 102cm for men, 88 for women)
2) Triglycerides (over 1.7mmol/L)
3) HDL (under 1.03mmol/L for men, 1.29mmol/L for women)
4) Fasting glucose (over 6.1mmol/L)
5) Blood pressure (over 130)
IDF criteria for metabolic syndrome
Mandatory component: central obesity (differs based on race, gender - Europid, Asian, Japanese)
Two or more of the following:
- Triglycerides (over 1.7mmol/L)
- HDL cholesterol (under 1.03mmol/L in men, under 1.29mmol/L in women)
- Blood pressure (over 130/85)
- Fasting blood glucose (over 5.6mmol/L)
Lipid-centric guidelines
NCEP ATPIII
Insulin resistance-centric guidelines
WHO, IDF
Effect of insulin on blood pressure.
Might contribute to hypertension
How might insulin contribute to hypertension?
Increases in plasma insulin concentration
within the physiological range stimulate
sodium reabsorption by the distal nephron
segments
Most widely accepted metabolic syndrome definition
IDF.
Based mostly on waist measurements.
Insulin receptor
Tyrosine kinase
Pathways activated by insulin receptor
1) PI-3 kinase
2) MAP kinase
MAP kinase role in insulin signalling
Insulin growth effects
PI-3 kinase role in insulin signalling
Insulin metabolic effects
Causative agent behind proposed metabolic syndrome aetiology
Defective PI-3 kinase pathway from insulin receptor
How could defective PI-3 kinase cause metabolic syndrome? 1) 2) 3) 4) 5) 6) 7) 8)
1) Defective PI-3 impacts glucose metabolism
2) Increase in blood glucose causes pancreas to release insulin
3) Increased insulin leads to hypertension, increase MAP Kinase signalling
4) MAP kinase leads to cytokine release
5) Cytokine release increases 11beta HSD-1 release
6) 11beta HSD-1 leads to increased corticosterone production
7) Cytokines, corticosterones increase hepatic VLDL levels
8) This leads to increased plasma triglycerides
