Lecture 18: Metabolic syndrome

Question 1

Define insulin resistance:

Answer 1

Given insulin conc. -> Subnormal glucose response

i.e high insulin with normal/high glucose

Question 2

Where can insulin resistance occur?

Answer 2

pre-receptor, receptor or post receptor (most common)

Precedes diabetes

Question 3

What is insulin resistance associated with?

Answer 3

1. Obesity
2. Type 2 diabetes
3. Metabolic syndrome

Question 4

Insulin resistance may be recognised due to the metabolic syndrome cluster, describe this:

Answer 4

Possibly fetal programming or genetic predisposition along with:

• Excess energy intake
• Decreased physical activity leads to:

TRUNCAL OBESITY
= INSULIN RESISTANCE

leads to:

• Glucose intolerance (T2D)
• Hypertension
• Fatty liver
• Dyslipidemia
• Endothelial dysfunction (inflam markers (procoagulant)

Question 5

What must a pt have to be said to have the metabolic syndrome cluster?

Answer 5

Central obesity (waist measures)

+2 of:

• Hypertension
• abnormal glucose
• high triglycerides
• Low HDL cholesterol

Question 6

Why does fat deposition matter?

Answer 6

Can be fat on the outside of fat on the inside. Inside fat matters most.

Question 7

What can tell us if a patient has insulin resistance?

Answer 7

1. Metabolic syndrome cluster
2. Acanthosis nigricans (pits, neck darken)
3. PCOS

Question 8

What causes insulin resistance?

Answer 8

• Increased visceral fat, stored TG and large adipocytes
• Large adipocytes are resistant to insulins ability to suppress lipolysis.
• Inc. lipolysis = increased non-esterfied FA (NEFA) and glycerol
• NEFA and Glycerol, plus proinflam cytokines from visceral adipose tissue (i.e TNFa and IL6) aggrevate insulin resistance in muscle and liver.
• (Might also cause lipotoxicity to beta cell)

Question 9

Are adiponectin and/or resistin implicated in insulin resistance?

Answer 9

• Adiponectin deficiency may cause development of insulin resistance
• Resistin is secreted by adipocytes of obese mice and decreases adipocyte glucose uptake….

Question 10

What happens to the insulin signalling in insulin resistance?

Answer 10

In insulin resistant states, insulin signalling is blocked by inhibition of p/ph of insulin receptor substrate proteins

Question 11

insert slide 31

Answer 11

plz

Question 12

Whats the impact of insulin resistance on glucose?

Answer 12

• Hepatic glucose output is not suppressed
• IMGU in muscle is reduced
• Thus only hyperinsulinaemia can maintain normal glucose levels

Question 13

Whats the impact of insulin resistance on fat?

Answer 13

Metabolic - rise in FFA, TGs (dyslipidaemia)

Hormones - Adipocytokines

Question 14

What are the consequences of insulin resistance?

Answer 14

Glucose rises -> Glucose toxicity in beta cells
FFA rise -> Lipotoxicity in beta cell, liver and muscle

Failing beta cells: Poor acute / first phase insulin release = post prandial hyperglyceamia
= Alpha cell dysregulation and hyperglucogonaemia

Question 15

Whats the critical step in going from insulin resistance to type two diabetes?

Answer 15

Beta cell dysfunction critical step in pathogenesis of T2D

Dec. beta cell mass = genetic or intrauterine

Dec. beta cell function = Less pulses, lipo and glucotoxicity, incretin dysfunction

BETA CELL DYSFUNCTION IS PROGRESSIVE

Question 16

Beta cell destruction is what sort of process?

Answer 16

Progressive

Question 17

insert slide 41

Answer 17

thanks

Question 18

What is DM?

Answer 18

Metabolic disorder characterised by the presence of hyperglyceamia due to defective insulin secretion, insulin action or both.

or

disorder of premature widespread atherosclerosis with hyperglyceamia as an assocaited feature (waaat)

Question 19

What range of fasting blood glucose is referred to as impaired glucose tolerance?

Answer 19

5.5-7mmol/L

Question 20

What is seen with an OGTT? insert slide 46 when blood glucose is measured

Answer 20

• An obsese normal person will handle glucose the same as a lean normal
• A lean or obese type 2 diabetic will not handle the oral glucose tolerance test

Question 21

What is seen on a OGTT when blood insulin is measured? (slide 50)

Answer 21

• A lean T2D will have very little insulin produced.
• An obese normal will have a more pronounced insulin release than lean normal.
• An obese type 2 diabetic will not have the acute phase insulin release and will gradually achieve a somewhat decent insulin level

Question 22

What is the HBA1C diagnostic criteria for diabetes?

Answer 22

Normal <40mmol/mol
Abnormal 41-49
Diabetes 50+

And/or fasting glucose >7mmol/L

Question 23

Is treatment of diabetes dependent on type?

Answer 23

No, depends on blood glucose levels.

Question 24

What are the microvascular and macrovascular complications of diabetes?

Answer 24

Microvascular

• Retinopathy
• Peripheral neuropathy (mono and autonomic)
• Nephropathy

Macrovascular

• IHD
• PVD
• CVA

Question 25

What are the risk factors for atherosclerosis cluster?

Answer 25

Diabetes + Hypertension + Dyslipidemia + Smoking

= Cerebrovascular disease (CVD), IHD, peripheral vascular disease (CVD)

NB better glyceamic control alone only has modest effects

Important to address all CVD risk factors

Question 26

What does the typical patient with type 2 diabetes look like?

Answer 26

• Obese
• Metabolic syndrome features
• Family history of type 2 diabetes
• Older
• Doesnt need insulin for 5-10 years post diagnosis

Question 27

How is diabetes managed?

Answer 27

• Diet + exercise

Meds of glucose control

• Insulin
• Metformin
• Sulphonyurea
• Insulin incretin therapy
• SGLT2 inhibitors
• Attend to BP, lipids, smoking etc