Metabolic syndrome

Question 1

What is metabolic syndrome?

Answer 1

a cluster of closely related metab disorders increasing the risk of development of T2DM and CVD:

• Abdominal adiposity
• Insulin resistance and high fasting blood glucose (IFG)
• Dyslipidemia
• HTN

Question 2

What characterized MetS diagnosis (3 criteria)?

Answer 2

Central obesity = waist circumference
Men >= 102cm, W >= 88cm
AND any of the two factors below:
- Plasma triglycerides >1.7mmol/L
- Plasma HDL-C men <1.0, women <1.3mmol/L
- Blood pressure: >130 systolic or >85 diastolic
- Fasting blood glucose >5.6mmol/L

Question 3

Describe the pathophysiology of metabolic syndrome

Answer 3

Abnormal liver function:
- increase hepatic glucose output, glucose uptake and fatty acid uptake
Increase conversion of FA into TG and VLDL which contribute to fatty liver disease and heart disease
Pancreatic islet mass due to exhaustion of hyperinsulinemia which will result in pre-diabetes followed by overt diabetes
Abnormal visceral adipose
- Decrease glucose uptake
- Increase lipid uptake which will be stored as fat leading to more insulin resistance development
- Increased lipolysis will release more FFA causing systemic lipotoxicity, accumulation of adipocytes will trigger macrophage building up CRP levels leading to complications of chronic diabetes
Abnormal muscle function will decrease glucose uptake and increase FA uptake
Changes in gut hormones
- Decrease GLP-1 which will decrease insulin action: inhibit glucagon release, stimulate insulin release and increases insulin sensitivity

Question 4

How is MetS linked with insulin resistance?

Answer 4

Insulin resistance is central to MetS abnormalities
Adipose tissue macrophage will release inflammatory cytokines that act on surrounding adipocytes impairing insulin action and promoting the release of FFA

Question 5

Why does lipid accumulation affect insulin?

Answer 5

Excess body fat and “spillover” can cause lipid accumulation in hepatocytes, skeletal muscles, visceral adipocytes and heart
Lipid accumulation in hepatocytes: hepatosteatosis (fatty liver or NAFLD), drives the formation of VLDL
Lipid accumulation in muscle: myosteatosis (fat infiltration in muscle) causing insulin resistance reducing glucose uptake

Question 6

What effect does insulin resistance have on dyslipidemia?

Answer 6

Insulin resistance will increase TG synthesis due to increase lipogenesis, excess FFA will enter the liver stimulating VLDL synthesis and decreasing HDL formation leading to loss of Apo-A1 in kidney. All resulting in hyperTG

Question 7

Does MetS pose as a higher risk of CVD than other combinations of illnesses?

Answer 7

Each component will increase the risk, as they all feed off each other causing high immune stress
The presence of MetS should be an indicator to clinicians to evaluate other components.