T2DM Flashcards
What is the histological picture of T2DM?
amyloid dispostition in islet cells
What causes T2DM?
genetic predisposition
obesity
lifestyle factors
What happens to beta cells in T2DM?
compensatory B cell hyperplasia
How is T2DM diagnosed?
Fasting plasma glucose (FPG) >7 mmol/L
Random plasma glucose ≥11.1 mmol/L
What is the target HbA1c?
below 48
What is the first line drug for T2DM?
metformin
What is the action of metformin?
decreases hepatic gluconeogenesis and increases peripheral glucose uptake by stimulating AMP activated protein kinase
can cause weight loss
What are the side effects of metformin?
lactic acidosis
GI upset
What drugs can be added on to Metformin?
Sulphonylurea - Glipizide and Glicizide Thiazolidinine - Glitazone DPP-4 inhibitors - Sitagliptin Incretin analogues - Extenatide SGLT-2 inhibitors - Empagliflozin
Describe the action of SGLT-2 inhibitors?
selectively blocks reabsorption of glucose by SGLT-2 in the proximal tubule of the kidney nephron
causes glucosuria
s.e. UTI
Describe the action of TZDs?
agonist of PPARy making the PPARy-RXR complex that encodes for the transcription factor that binds to DNA to promote expression of genes involved in insulin signalling and lipid metabolism
causes weight gain and fluid retention
reduces insulin resistance
reduced hepatic gluconeogenesis
Describe the action of sulphonureas?
block the KATP channel by displacing the binding of ADP-Mg from the SUR1 subunit
this stimulates insulin release
may cause hypoglycaemia
Describe the actions of Glinides?
bind to SUR1 to close the KATP channel and trigger insulin release
avoided in pregnancy, breast feeding, severe hepatic impairment
Describe the action of DPP-4 inhibitors?
prolong the effect of GLP-1 and GIP (inhibited by DPP-4)
this enhaced insulin secretion from beta cells and decreases glucagon release
Describe the action of incretin analogues?
mimic the action of GLP-1 and bind as an agonist to GPCR GLP-1 receptors to increase intracellular cAMP concentration in beta cells
cause weight loss
How does T2DM cause microvascular complications?
reduced blood flow causing damaged nerves
What are the 4 types of neurophathy that T2DM can cause?
peripheral
autonomic
focal
proximal
Describe autonomic neuropathy?
affects the nerves regulating the heart rate and BP as well as the control of internal organs e.g. those involved with gastric mobility, respiratory function, urination, sexual function and vision
Give examples of problems caused by autonomic neuropathy?
gastroperesis
sweat glands lose their ability to regulate temperature
postural hypotension
Describe peripheral neuropathy?
tingling and pain
loss of balance and coordination
sensitive to touch
Describe focal neuropathy?
appears suddenly and affects specific nerves
commonly on head, torso or leg (sometimes behind eye - Bells palsy)
Describe Proximal neuropathy?
pain in thighs/buttocks/legs
What is diabetic nephropathy?
a progressive kidney disease causing damage to the capillaries in the kidneys glomeruli
causes protein leakage and imprired renal function
How is diabetic nephropathy screened for?
albumin creatine ratio
- if they have microalbinuria or proteinuria - commence ACEI or ARB
What are the stages of diabetic retinopathy?
mild non proliferative - haemorrhages and microaneurysms
moderate non proliferative - haemorrhages, micro aneurysms and hard exudates
severe non proliferative - IRMA, venous bleeding, haemorrhages
proliferative
- new vessel formation, sudden change in vision
What is the treatment for diabetic retinopathy?
laser treatment for localised coagulation of blood cells/vessels
vitrectomy and anti-VEGF injections
What affect can diabetes have on cataract development?
develops earlier in diabetics
What can diabetes lead to in men?
erectile dysfunction
