Endo 16: Type II diabetes mellitus Flashcards
Define Diabetes Mellitus
State of chronic hyperglycemia sufficient to cause long term damage to specific tissues, notably the retina, kidneys, nerves + arteries
note: fasting glucose level >7mmol/L
What are 3 major factors that influence the pathophysiology of T2DM ?
- genetics
- intrauterine environment (causes epigenetic changes )
- adult environment
Insulin resistance + insulin secretion defects causes :
T2DM
What is MODY?
- maturity onset diabetes of the young
- autosomal dominant
- -> involves mutation of transcription factor genes glucokinase genes
- -> single gene hereditary condition
–> ineffective pancreatic B-cell insulin production
Insulin leads to _______
which stimulates the mitogenic pathway
what is the effect of this?
Insulin leads to DYSLIPIDAEMIA
which stimulates the mitogenic pathway
effect:
- causes smooth muscle cell hypertrophy
- -> causes increase in BP
- -> can cause microvascular disease
How is low birth rate linked to diabetes?
- low birth weight increase risk of impaired glucose tolerance + diabetes
–> epigenetic effect
As we age, we secrete more / less insulin
and we become more/ less insulin resistant
As we age, we secrete more insulin
because with age we become more insulin resistant
How might T2DM present?
- obesity
- insulin resistance
- insulins secretion deficiency
- hyperglycemia
- dyslipidaemia
- acute/chronic complication
How does insulin lower blood glucose level?
- by reducing HGO
what happens to HGO before and after a meal ?
before meal = HGO maintains blood glucose level at 4 mmol/L
after meal = insulin stops HGO
IN T2DM:
THERE IS INSUFFICIET INSULIN TO INHIBIT HGO + INSUFFICIENT INSULIN TO MOVE GLUCOSE INTO MUSCLE + FAT
-
what is the relationship between insulin sensitivity + insulin secretion in NORMAL individuals?
with age insulin sensitivity decreases
–> so insulin secretion increases to maintain normal blood glucose levels
i.e insulin resistance increases with age
what is the relationship between insulin sensitivity + insulin secretion in DIABETIC individuals?
with age insulin sensitivity decreases
–> but can’t increase insulin secretion sufficiently
What are major effects of insulin resistance?
- there is an increase HGO
- there is a decrease in glucose uptake into tissues
perturbation in gut microbiota
bacteria in gut modulates intermediary metabolism
- associate with obesity, T2DM
- involved in host signaling
- involved in bacterial lipopolysaccharides fermentation to short chain FA
What is a common side effect of diabetes treatments
except:
- weight gain
except metformin
How might T2DM present?
- osmotic symptoms
- infections
- screening test
if with complication
- acute: hyperosmolar coma
- chronic: Ischaemic heart disease, retinopathy
What are some microvascular complications associated with T2DM ?
- retinopathy
- nephropathy
- neuropathy
What are some macrovascular complications associated with T2DM ?
- ischemic heart disease
- cerebrovascular
- renal artery stenosis
What are some metabolic complications associated with T2DM ?
- lactic acidosis
- hyperosmolar
How would you manage T2DM?
- educate
- change diet
- pharmacological treatment
- complication screening
How would you change lifestlyle/diet of patients with T2DM?
- increase exercise
- reduce refined carb
- increase complex carb
- reduce fat
- increase unsaturated fat proportion
- increase soluble fibre
- less salt
How does Metformin act as a treatment method for T2DM?
- biguanide
- acts on LIVER
- reduced insulin resistance
- -> reduces HGO
- -> increases peripheral glucose disposal
note:
avoid if severe liver/heart/ mild renal failure
How does Sulphonylurea act as a treatment method for T2DM?
- they block the ATP sensitive K+ channel in Beta cell
- which causes depolarization
- activates VGCC
- causes Ca2+ influx
- which causes insulin secretion
