Metabolic Syndrome

Question 1

Define metabolic syndrome

Answer 1

Cluster of closely related metabolic disorders which increase the risk of developing T2DM and CVD when combining certain risk factors.

Question 2

What are the certain risk factors?

Answer 2

• Abdominal adiposity
• Insulin resistance and IFG
• Dyslipidemia
• Hypertension

Question 3

What is the true underlying metabolic problem in MetS?

Answer 3

Insulin resistance and impaired fasting blood glucose

Question 4

What is required to make a diagnosis of MetS?

Answer 4

Requires the presence of central obesity (as determined by WC and ethnic specificity) plus the 2 out of 4 specific factors

Question 5

In combination with central obesity, two out of which 4 factors must be present to make a diagnosis of MetS?

Answer 5

• High plasma TG
• Low plasma HDL
• High BP
• High fasted blood glucose or previously diagnosed with diabetes

Question 6

High TG?

Answer 6

> /= 1.7 mmol/L

Question 7

Low HDL men?Women?

Answer 7

Men <1.0

Women <1.3 mmol/L

Question 8

High BP?

Answer 8

> /= 130 systolic or >/= 85 mmHg diastolic

Question 9

High FBG?

Answer 9

> /= 5.6 mmol/L

Question 10

Typically, how does MetS develop?

Answer 10

Energy intake in excess of energy needs, and overtime

Question 11

MetS in the liver?

Answer 11

• More hepatic glucose output due to lack of inhibition from the liver.
• Increased gluconeogenesis and glycogenolysis (glucotoxicity)
• More glucose and FA uptake (greater dietary load) and more conversion to VLDL, NAFLD, heat disease
• Less HDL

Question 12

MetS in pancreas?

Answer 12

Pancreatic islet mass is increased as b-cell produce more insulin, followed by exhaustion

Question 13

What is overt diabetes?

Answer 13

Late stage diabetes following b-cell destruction or exhaustion

Question 14

MetS in adipose tissue?

Answer 14

• Insulin resistance, and deceased glucose uptake

- Increased lipid uptake while lipolysis increases, increase FFA –> Liver and systemic lipotoxicity.

Question 15

How is lepin affected in MetS?

Answer 15

Leptin increases proportionally with adipose tissue, but with resistance

Question 16

Adiponectin in MetS? What is it associated with

Answer 16

Decreases, associated with more insulin sensitivity and main action is in the liver

Question 17

MetS in muscle tissue?

Answer 17

Less glucose uptake (contributes to glucotoxicity), more FFA uptake for a source of fuel

Question 18

MetS on gut-peptides?

Answer 18

-GLP-1 decreases
-Incretins decrease
Ultimately feedback to the brain and alter satiety signals

Question 19

We know that insulin resistance is the underlying metabolic problem in MetS, but what may explain the development of insulin resistance?

Answer 19

Systemic low-grade inflammation

Question 20

What produces systemic low-grade inflammation?

Answer 20

Produced from adipose tissue, stimulates pro-inflammatory cytokine which will be secreted into circulation - stimulates liver to produce inflammatory proteins (acute-phase, CRP)

Question 21

(T/F) Insulin resistance is the sole cause of MetS

Answer 21

False, although it is central

Question 22

(T/F) MetS can be diagnosed without insulin resistance

Answer 22

True , however insulin resistance is present in most cases

Question 23

What is the proposed mechanism of MetS and accumulation of visceral fat?

Answer 23

• Visceral fat will increase FFA in liver.
• Excess of absorbed nutrients will travel through the hepatic portal vein and drained directly into the hepatic bloodsteam –> more fat stored, more lipolysis
• May cause NAFLD

Question 24

Proposed mechanism of inflammation and Mets?

Answer 24

• There is inflammation occurring in the adipose tissue (likely due to macrophage activation and infiltration into the liver)
• Many pro-inflammatory cytokines, located in the adipose tissue are linked to MetS

Question 25

What often acts together to produce MetS and increase cardiometabolic risk?

Answer 25

Insulin resistance, inflammation and increased lipolysis

Question 26

What is the ectopic fat storage hypothesis of insulin resistance>

Answer 26

Excess body fat and "spill-over" will cause lipid accumulation in hepatocytes, skeletal muscles, visceral adipocytes and heart INSTEAD of subcutaneous tissues

Question 27

What does the deposition of fat in non-subcutaneous tissues lead to?

Answer 27

-Insulin resistance, inflammation and altered functions

Question 28

What are the consequences of lipid accumulation in hepatocytes?

Answer 28

Hepatosteatosis (fatty liver or NAFLD) --> lead to an inflammation state, where fibrosis and cirrhosis will drive the formation of VLDL

Question 29

What are the consequences of lipid accumulation in muscle?

Answer 29

Myosteatosis (fat infiltration in muscle) --> Usually caused by a sedentary lifestyle or losing weight, where this may affect the quality of muscle, can cause insulin resistance

Question 30

How does insulin resistance result in dyslipidemia?

Answer 30

More lipolysis (as no longer inhibited by insulin) will result in more FFA brought to liver - and overproduction of VLDL. Increased CETP transfer to HDL and increased HDL uptake by liver - APO-A1 loss also occurs in the kidney

Question 31

Characteristic blood lipid profile of MetS?

Answer 31

Low HDL and high TG

Question 32

Does MetS confer a greater risk of CVD than any combination of its components?

Answer 32

Some clinicians believe that each components increases the risk additively or synergistically.

Question 33

What other evaluation algorithms should be used alongside MetS/

Answer 33

Framingham risk score, CANRISK

Question 34

What should MetS do?

Answer 34

Alert clinicians that the presence of 1 or more features should provoke the evaluation of other components.