Metabolic syndrome Flashcards
definition
a cluster of closely related metabolic disorders that INCRESE the risk of developing type 2 diabetes and CVD and combine the follow factors: abdominal adiposity, IR and high IFG, dyslipidemia and HPT
diagnosis of MetS
3 criteria must be met
- has to have central obesity –> waist circumference >102 men and >88 women
- then 2 of these:
1. plasma TG >1.7
2. plasma HDL < 1 or <1.3 women
3. BP > 130systolic or > 85 diastolic
4. fasting BG > 5.6 mol/L ( or diagnosis with diabetes
how does MetS start
excess food intake leading to excess insulin secretion leads to excess glucose uptake–> obesity –> then IR
diabetic patients will have MetS if what?
have obesity and 1 other factor
MetS in the Liver
abnormal function
- glucotoxicity from increased gluconeogeneis and glycogenolysis and increased CHO intake
- more FFA –> more conversion to VLDL and some stay in the liver = NAFLD
- less HDL
MetS in the pancreas
increase in mass as pancreatic Cells are over producing insulin
MetS in adipose tissue
IR (HAM- heart, adipose and muscle- GLUT4) - so less glucose uptake, and increase lipolysis- (bc no anti-lipolytic signal from insulin) so more FFA in circulation (lipotoxicity)
- increase in leptin (but resistance)
- adiponectin decreases
what does increase in leptin during MetS cause? why is there resistence?
leptin is a hormone released by adipose cells and leptin levels increase when adiposity increases
- leptin acts on the hypothalamus to say “ we have enough fat” but in obesity we often see leptin resistance –> brain thinks starving –> weight gain
why does adiponectin decrease in MetS and what does this cause?
adiponectin is released by adipose tissue and acts opposite of leptin in a sense bc when the body has high fat it decreases - and has been associated with diabetes and health issues - less insulin sensitive and says ( we have enough fat- less glucose uptake) but when body has low fat it increases - which is a good thing bc associated with positive health outcomes, greater insulin sensitivity and less risk of CVD- saying we have the capacity to store fat
In MetS adiponectin decreases –>
-in MetS associated with IR and role is primarily in the liver where a decrease in it will cause:
1. increase in gluconeogenesis (more glucotoxicity)
2. less glucose uptake (exacerbates IR)
3. BW increase ( why?)
4. less insulin sensitivity
why does BW increase with low levels of adiponectin?
there are many anti-oxidant and beneficial health benefits to adiponectin- a decrease in it is associated with IR and obesity and health complications ( it is inversely associated with BW)
adiponectin levels
inversely related to body fat ( high body fat= low levels)
- high levels may increase HDL, decrease LDL, and improves IR
does IR lead to weight gain
polyphagia
MetS in muscle tissue
less glucose uptake ( IR GLUT 4)
-more glucose in circulation ( glucotoxicity, and much greater FFA uptake for fuel )
MetS in gut-peptides
GLP-1 decreases
which leads to less incretin secretion will decrease (less insulin secretion stim)
incretins
gut peptides that stimulate insulin secretion
so in MetS less incretins means less insulin, more glucagon and less GI motility and less sensitivity to insulin
pancreatic hormones in MetS
increase glucagon and increase insulin ( but with resistance) –> abnormal satiety ( higher peak levels and loner in circulation–> leads to abnormal homeostasis and hedonic response
adipose tissue in MetS
less glucose uptake but much greater FFA uptake –> weight gain and fat storage leading to systemic inflammation
–> increase lipolysis –> systemic lipotoxicity in cells
–> LPL is insulin dependent so hyperinsulemia cause more fat storage?
what is the likely cause of IR in MetS
low-grade systemic inflammation
- produced from adipose tissue, stimulation pro-inflammatory cytokines which stimulates the liver to produce inflammatory proteins ( acute-phase proteins, CRP)
can you have MetS without IR?
yes- while it is a very central cause it is not the sole cause- however present in most cases
why inflammation in adipose tissue?
large amounts of macrophage activation and infiltration into the liver –> pro-inflammatory cytokines linked to IR, especially locally in adipose tissue. IR and increased lipolysis around the adipose tissue creates the perfect environment fro MetS
Ectopic fat storage (another hypothesis of insulin resistance)
excess fat and spillover causing lipid accumulation in hepatocytes, skeletal muscle, visceral adipocytes and heart ( instead of subcutaneous fat storage- which has low risk) this abnormal deposition casues IR, inflammation and altered functions
what is so bad about lipid accumulation in hepatocytes
NAFLD–> leads to inflammation state s fibrosis and cirrhosis drives the formation of VLDL
what so bad about lipid accumulation in muscle?
myosteatosis affects muscle strength and can caused IR–> reducing glucose uptake, in some instances we see lipid accumulation in people when losing weight
IR and dyslipidemia
more lipolysis (IR) results in more FFA being brought to the liver, which results in the overproduction of VLDL. like in obesity, there is an increased CETP and this decreases HDL (increase HDL into the liver through hepatic lipase and APO-A1 loss within the kidney
what casues metabolic syndrome?
debated but significant causative factors are IR and central obesity
why is it important to diagnosis MetS early?
it is the driving force behind 2 of the greatest killers/edidemics worldwide= diabetes and CVD
what is the bad LDL
sm LDL (small dense LDL)
what should treatment look like once diagnosis?
should be aggressive and uncompromising in order to reduce the risk of CVD and Diabetes - patients should undergo a full CV risk assessment and undergo primary management: lifestyle modifications - calorie restriction to achieve 5-10% weight loss in first year, increase PA and change dietary composition
secondly- drug therapy may be used
treatment for MetS? if you have different criteria met, does therapy look different?
yes, treatment of the individual components- for example if have athlergenic dyslipidemia treat this but if have elevated BP- target this
what is definition of a syndrome? why is this a syndrome and not a disease?
syndrome= “group or recognizable pattern of symptoms or abnormalities that indicate a particular trait or disease”
is metabolic syndrome a valid indicator of CVD risk?
it is not an absolute risk predictor; however as a general rule, the risk for major CVD events is 2x in patients with MetS compared to non MetS patients. the risk for diabetic patients is 5 fold. and ppl with metS and diabetes possess and even higher risk–> this demonstrates an additive relationship.
what’s best way to prevent CVD and diabetes risks?
lifestyle is by far the best, but pharamacological agents may be appropriate is lifestyle adjustments fail
how can metS be diagnosed in clinical practice?
initial step is waste circumference –> if this is above, then measure BP, FPG, TG and HDL
