Metabolic Syndrome

Question 1

What is the definition of metabolic syndrome?

Answer 1

A cluster of closely related metabolic disorders increasing the risk of development of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD):

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

Formerly known as Syndrome X

Question 2

What are the 3 criteria for MetS diagnosis?

Answer 2

1. Central obesity = waist circumference (ethnicity specific)
   Men ≥ 102 cm, women ≥ 88 cm (Caucasians in US and Canada)
2. • 2 of these four factors:
     - Plasma triglycerides * ≥ 1.7 mmol/L
     - Plasma HDL-C * Men <1.0, women <1.3 mmol/L
     - Blood pressure * ≥ 130 systolic or ≥85 mmHg diastolic
     - Fasting blood glucose * ≥ 5.6 mmol/L; Or previously diagnosed diabetes

**or drug treatment

Question 3

What is the proposed mechanism of MetS?

Answer 3

visceral adiposity –> insulin resistance
visceral adiposity + insulin resistance –> Type 2DM –> CVD

• Insulin resistance is central to MetS abnormalities, but is probably not the sole cause
• Direct venous drainage of visceral fat in hepatic portal vein –> increase hepatic FFA delivery
• Adipose tissue macrophage content linked with IR:
  - Release inflammatory cytokines that act on
  surrounding adipocytes –> impairing insulin action
  and promoting release of FFA

Question 4

What is Ectopic fat storage “overflow hypothesis”?

Answer 4

excess body fat and “spillover” causing lipid accumulation in hepatocytes, skeletal muscles, visceral adipocytes and heart (instead of subcutaneous adipose tissue)
–> insulin resistance, inflammation and altered functions

Question 5

What does Ectopic fat storage “overflow hypothesis” lead to in muscle and hepatocyes?

Answer 5

lipid accumulation in hepatocytes:

• hepatosteatosis (fatty liver or NAFLD)
• drives the formation of VLDL

lipid accumulation in muscle

• myosteatosis (fat infiltration in muscle)
• cause IR: reduce glucose uptake