Lecture 18: Metabolic syndrome Flashcards
Define insulin resistance:
Given insulin conc. -> Subnormal glucose response
i.e high insulin with normal/high glucose
Where can insulin resistance occur?
pre-receptor, receptor or post receptor (most common)
Precedes diabetes
What is insulin resistance associated with?
- Obesity
- Type 2 diabetes
- Metabolic syndrome
Insulin resistance may be recognised due to the metabolic syndrome cluster, describe this:
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)
What must a pt have to be said to have the metabolic syndrome cluster?
Central obesity (waist measures)
+2 of:
- Hypertension
- abnormal glucose
- high triglycerides
- Low HDL cholesterol
Why does fat deposition matter?
Can be fat on the outside of fat on the inside. Inside fat matters most.
What can tell us if a patient has insulin resistance?
- Metabolic syndrome cluster
- Acanthosis nigricans (pits, neck darken)
- PCOS
What causes insulin resistance?
- 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)
Are adiponectin and/or resistin implicated in insulin resistance?
- Adiponectin deficiency may cause development of insulin resistance
- Resistin is secreted by adipocytes of obese mice and decreases adipocyte glucose uptake….
What happens to the insulin signalling in insulin resistance?
In insulin resistant states, insulin signalling is blocked by inhibition of p/ph of insulin receptor substrate proteins
insert slide 31
plz
Whats the impact of insulin resistance on glucose?
- Hepatic glucose output is not suppressed
- IMGU in muscle is reduced
- Thus only hyperinsulinaemia can maintain normal glucose levels
Whats the impact of insulin resistance on fat?
Metabolic - rise in FFA, TGs (dyslipidaemia)
Hormones - Adipocytokines
What are the consequences of insulin resistance?
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
Whats the critical step in going from insulin resistance to type two diabetes?
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
Beta cell destruction is what sort of process?
Progressive
insert slide 41
thanks
What is DM?
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)
What range of fasting blood glucose is referred to as impaired glucose tolerance?
5.5-7mmol/L
What is seen with an OGTT? insert slide 46 when blood glucose is measured
- 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
What is seen on a OGTT when blood insulin is measured? (slide 50)
- 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
What is the HBA1C diagnostic criteria for diabetes?
Normal <40mmol/mol
Abnormal 41-49
Diabetes 50+
And/or fasting glucose >7mmol/L
Is treatment of diabetes dependent on type?
No, depends on blood glucose levels.
What are the microvascular and macrovascular complications of diabetes?
Microvascular
- Retinopathy
- Peripheral neuropathy (mono and autonomic)
- Nephropathy
Macrovascular
- IHD
- PVD
- CVA
