Metabolic syndrome- ?? Flashcards
Metabolic syndrome- definition
WHat was it formerly known as??
A cluster of closely related metabolic disorders increasing the risk of development of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD):
◦Abdominal adiposity- central factor of this condition
◦Insulin resistance and high fasting blood glucose (IFG- impaired fasting glucose)
◦Dyslipidemia
◦Hypertension
◦Formerly known as Syndrome X
It is easier to measure __ than insulin resistance
It is easier to measure FBG than insulin resistance
What can be measure as a marker of insulin in fed state (aka indicate insulin resistance)
Fasted insulin levels
How long does OGGT take?
3h
What are the MetS diganosis criteria
1. Central obesity
Men ≥ 102 cm, women ≥ 88 cm (Caucasians in US and Canada)
Asian, Ethnic South and Central Americans: Men≥ 90 cm. Female ≥80cm
Suggested by IDF cut-offs for europeoids are stricter: Men≥ 94 cm. Female ≥80cm
+ 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 which suggests prediabetes (Or previously diagnosed diabetes)
* or drug treatment for this criteria aka if drug treatment for this conditions was prescribed, this is considered as one of the criteria for the metabolic syndrome
Normal metabolic homeostasis
Chnages in homeostasis during metabolic syndrome
Starts with excessive energy intake, resulting in weight gain-> abdominal adiposity
As a response to food ingested, insulin is normally secreted; in this case it occurs it higher level and for a longer duration
Insulin resistance will also be present
Abnormal satiety signals due to disruption of hedonic and homeostatic response
Disruption in autonomic nervous system and central regulation of metabolsim also contibutes to abnormal satiety as well as abnormal nutrient sensing
GI
- Gut hormones are secreted. In this case secretions are affected
- GLP-1 (glucagon like peptide-1) response is depressed-> less is secreted
- This gut peptide is an incretin hormone (stimulates insulin secretion, inhibition of glucagon release, increased insulin sensitivity and GI motility)
- Increased dietary fats and sugar absorption
- Increased gut motility
Liver will be affected
- This is also related to insulin resistance
- More hepatic glucose ouput due to absence of inhibition by insulin on glucose production
- Higher glucose uptake by the liver as more CHO/glucose is ingested
- More of ths excess glucose is converted into Tg-> VLDL-> circulation
- More FA uptake occurs as more fat is consumed and due to higher lipolysis of TG in adipose tissue due to the absence of inhibition of lipolysis by insulin -> TG-rich VLDL
Pancreatic Islet mass (b-cells) will increase-> hyperinsulinemia (which is associated with central obesity)
Hyperinsulinemia will eventually result in insulin exhaustion -> overt diabetes
GI
Gretaer fat and glucose intake-> more absorbed
Increased gut motility
Visceral adipose
Less glucose uptake due to insulin resistance
Greater lipid uptake due to higher intake)
Hihgr lipoylsi-> increased FFA in the circulation-> systemic lipotoxicity as these FFA are taken up by other organs and cause lipotoxicity of these cells
Muscles
- Higher FA and lower glucose uptake
Less anti-inflammatory and more pro-inflammatory cytokines are released-> marginal inflammation state
Adipose tissue normally secretes hormones
- Now there’s dysregulation-> more leptin secretion + leptin resistance (no leptin satiety signaling), decreased energy expenditure
- Less adiponectin secretion (hormone associated with insulin sensitivity)-> increased gluconeogenesis, Decreased glucose uptake, decreased insulin sensitivity, increased body weight, decrease endothelial function
What are the main components of metabolic syndrome
Visceral adiposity and insulin resistance are the main components which lead to cardiometabolic risk
Cardiometabolic risk is a condition in which the possibilities of developing atherosclerotic cardiovascular (CV) disease and diabetes mellitus are significantly enhanced as a consequence of the presence of insulin resistance and visceral adiposity
2 Mechanisms, independent of insulin resistance that can also contribute to MeS:
1) With accumulation of visceral fat-> Direct venous drainage of visceral fat in hepatic portal vein to the liverè increase hepatic FFA delivery to the liver
2) Adipose tissue macrophage content linked with insulin resistance:
Release inflammatory cytokines that act on surrounding adipocytes -> impairing insulin action and promoting release of FFA
What is ectopic fat storage
storage of fat where it should not be stored (not in subcutaneous fat tissue)
Describe Ectopic fat storage aka “overflow hypothesis”
- Excess body fat and “spillover” causing lipid accumulation in hepatocytes, skeletal muscles, visceral adipocytes and heart (instead of subcutaneous adipose tissue)
- All of this results insulin resistance, inflammation and altered functions
lipid accumulation in hepatocytes:
- hepatosteatosis (fatty liver or NAFLD)- deposition of fat in the liver; not a sign of other diseases
- drives the formation of VLDL
lipid accumulation in muscle
- myosteatosis (fat infiltration in muscle)
- cause IR: reduce glucose uptake in the muscles
- Location of fat accumulation in muscle cells is important
Does being overweight = MeS
Overweight people who store excess fat in subcutaneous tissues only do not have an increased risk of MeS
Lipid accumulation can occur in organs and muscle->
Lipid accumulation can occur in organs and muscle-> impairment of function and insulin resistance in tissues+ inflammation
Insulin resistance and dyslipidemia
- Insulin action on adipocytes is inhibited (no inhibition of insulin sensitive lipase) such as lipolysis occurs at higher rate releasing FFA into the circulation
- FFA will go to the liver and will me made into TG and packaged into VLDL-> more VLDL in the circulation
- Exchnage via CETP of CE to VLDV from HDL and TG into HDL
- This result in increased clearance of HDL by Hepatic lipase -> decreased HDL; increased adipose tissue
- More cholesterol will be found in LDL; these will become Small Dense LDL via action of lipase (the most atherogenic LDL)
Does MetS confers greater risk of CVD than any combination of its components?
◦Each component increases the risk additively, perhaps with greater interaction (synergism).
Other risk evaluation algorithms should also be considered: Framingham Risk Score, CANRISK.
