Metabolic Syndrome Flashcards
Define metabolic syndrome
Cluster of closely related metabolic disorders which increase the risk of developing T2DM and CVD when combining certain risk factors.
What are the certain risk factors?
- Abdominal adiposity
- Insulin resistance and IFG
- Dyslipidemia
- Hypertension
What is the true underlying metabolic problem in MetS?
Insulin resistance and impaired fasting blood glucose
What is required to make a diagnosis of MetS?
Requires the presence of central obesity (as determined by WC and ethnic specificity) plus the 2 out of 4 specific factors
In combination with central obesity, two out of which 4 factors must be present to make a diagnosis of MetS?
- High plasma TG
- Low plasma HDL
- High BP
- High fasted blood glucose or previously diagnosed with diabetes
High TG?
> /= 1.7 mmol/L
Low HDL men?Women?
Men <1.0
Women <1.3 mmol/L
High BP?
> /= 130 systolic or >/= 85 mmHg diastolic
High FBG?
> /= 5.6 mmol/L
Typically, how does MetS develop?
Energy intake in excess of energy needs, and overtime
MetS in the liver?
- 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
MetS in pancreas?
Pancreatic islet mass is increased as b-cell produce more insulin, followed by exhaustion
What is overt diabetes?
Late stage diabetes following b-cell destruction or exhaustion
MetS in adipose tissue?
- Insulin resistance, and deceased glucose uptake
- Increased lipid uptake while lipolysis increases, increase FFA –> Liver and systemic lipotoxicity.
How is lepin affected in MetS?
Leptin increases proportionally with adipose tissue, but with resistance
Adiponectin in MetS? What is it associated with
Decreases, associated with more insulin sensitivity and main action is in the liver
MetS in muscle tissue?
Less glucose uptake (contributes to glucotoxicity), more FFA uptake for a source of fuel
MetS on gut-peptides?
-GLP-1 decreases
-Incretins decrease
Ultimately feedback to the brain and alter satiety signals
We know that insulin resistance is the underlying metabolic problem in MetS, but what may explain the development of insulin resistance?
Systemic low-grade inflammation
What produces systemic low-grade inflammation?
Produced from adipose tissue, stimulates pro-inflammatory cytokine which will be secreted into circulation - stimulates liver to produce inflammatory proteins (acute-phase, CRP)
(T/F) Insulin resistance is the sole cause of MetS
False, although it is central
(T/F) MetS can be diagnosed without insulin resistance
True , however insulin resistance is present in most cases
What is the proposed mechanism of MetS and accumulation of visceral fat?
- 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
Proposed mechanism of inflammation and Mets?
- 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
What often acts together to produce MetS and increase cardiometabolic risk?
Insulin resistance, inflammation and increased lipolysis
What is the ectopic fat storage hypothesis of insulin resistance>
Excess body fat and “spill-over” will cause lipid accumulation in hepatocytes, skeletal muscles, visceral adipocytes and heart INSTEAD of subcutaneous tissues
What does the deposition of fat in non-subcutaneous tissues lead to?
-Insulin resistance, inflammation and altered functions
What are the consequences of lipid accumulation in hepatocytes?
Hepatosteatosis (fatty liver or NAFLD) –> lead to an inflammation state, where fibrosis and cirrhosis will drive the formation of VLDL
What are the consequences of lipid accumulation in muscle?
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
How does insulin resistance result in dyslipidemia?
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
Characteristic blood lipid profile of MetS?
Low HDL and high TG
Does MetS confer a greater risk of CVD than any combination of its components?
Some clinicians believe that each components increases the risk additively or synergistically.
What other evaluation algorithms should be used alongside MetS/
Framingham risk score, CANRISK
What should MetS do?
Alert clinicians that the presence of 1 or more features should provoke the evaluation of other components.
