Metabolic syndrome

Question 1

definition

Answer 1

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

Question 2

diagnosis of MetS

Answer 2

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

Question 3

how does MetS start

Answer 3

excess food intake leading to excess insulin secretion leads to excess glucose uptake–> obesity –> then IR

Question 4

diabetic patients will have MetS if what?

Answer 4

have obesity and 1 other factor

Question 5

MetS in the Liver

Answer 5

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

Question 6

MetS in the pancreas

Answer 6

increase in mass as pancreatic Cells are over producing insulin

Question 7

MetS in adipose tissue

Answer 7

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

Question 8

what does increase in leptin during MetS cause? why is there resistence?

Answer 8

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

Question 9

why does adiponectin decrease in MetS and what does this cause?

Answer 9

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

Question 10

why does BW increase with low levels of adiponectin?

Answer 10

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)

Question 11

adiponectin levels

Answer 11

inversely related to body fat ( high body fat= low levels)

- high levels may increase HDL, decrease LDL, and improves IR

Question 12

does IR lead to weight gain

Answer 12

polyphagia

Question 13

MetS in muscle tissue

Answer 13

less glucose uptake ( IR GLUT 4)

-more glucose in circulation ( glucotoxicity, and much greater FFA uptake for fuel )

Question 14

MetS in gut-peptides

Answer 14

GLP-1 decreases

which leads to less incretin secretion will decrease (less insulin secretion stim)

Question 15

incretins

Answer 15

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

Question 16

pancreatic hormones in MetS

Answer 16

increase glucagon and increase insulin ( but with resistance) –> abnormal satiety ( higher peak levels and loner in circulation–> leads to abnormal homeostasis and hedonic response

Question 17

adipose tissue in MetS

Answer 17

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?

Question 18

what is the likely cause of IR in MetS

Answer 18

low-grade systemic inflammation
- produced from adipose tissue, stimulation pro-inflammatory cytokines which stimulates the liver to produce inflammatory proteins ( acute-phase proteins, CRP)

Question 19

can you have MetS without IR?

Answer 19

yes- while it is a very central cause it is not the sole cause- however present in most cases

Question 20

why inflammation in adipose tissue?

Answer 20

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

Question 21

Ectopic fat storage (another hypothesis of insulin resistance)

Answer 21

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

Question 22

what is so bad about lipid accumulation in hepatocytes

Answer 22

NAFLD–> leads to inflammation state s fibrosis and cirrhosis drives the formation of VLDL

Question 23

what so bad about lipid accumulation in muscle?

Answer 23

myosteatosis affects muscle strength and can caused IR–> reducing glucose uptake, in some instances we see lipid accumulation in people when losing weight

Question 24

IR and dyslipidemia

Answer 24

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

Question 25

what casues metabolic syndrome?

Answer 25

debated but significant causative factors are IR and central obesity

Question 26

why is it important to diagnosis MetS early?

Answer 26

it is the driving force behind 2 of the greatest killers/edidemics worldwide= diabetes and CVD

Question 27

what is the bad LDL

Answer 27

sm LDL (small dense LDL)

Question 28

what should treatment look like once diagnosis?

Answer 28

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

Question 29

treatment for MetS? if you have different criteria met, does therapy look different?

Answer 29

yes, treatment of the individual components- for example if have athlergenic dyslipidemia treat this but if have elevated BP- target this

Question 30

what is definition of a syndrome? why is this a syndrome and not a disease?

Answer 30

syndrome= "group or recognizable pattern of symptoms or abnormalities that indicate a particular trait or disease"

Question 31

is metabolic syndrome a valid indicator of CVD risk?

Answer 31

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.

Question 32

what's best way to prevent CVD and diabetes risks?

Answer 32

lifestyle is by far the best, but pharamacological agents may be appropriate is lifestyle adjustments fail

Question 33

how can metS be diagnosed in clinical practice?

Answer 33

initial step is waste circumference --> if this is above, then measure BP, FPG, TG and HDL