T2DM Flashcards
How do you work out the osmolality?
Cations + anions + glucose + urea
However there’s too much anions so you just double the cations (sodium and potassium) then add glucose and urea
Normal osmolality
Na + K x 2 = 288
+ 4 + 4 for glucose and urea
296mil osmoles per kg
Why don’t they get acidosis?
They have enough insulin to suppress ketoacidosis
Why do over half the patients in the UK not know they have diabetes?
They think the polydipsia/polyuria is due to UTI/prostate trouble
What are the three microvascular complications?
Retinopathy
Nephropathy
Neuropathy
Features of macrovascular complications
Ischemic heart disease
Cerebrovascular disease
Peripheral gangrene
What are the features of background retinopathy?
Hard exudates
Microaneurysms
Blot haemorrhages
Why does the patient see fine despite background retinopathy?
Because the macula is preserved
Treatment for background retinopathy?
Improve BLOOD GLUCOSE CONTROL
not blood pressure (this is for nephropathy)
What are hard exudates?
cholesterol deposits
What is the difference between cotton wool spots and hard exudates?
Cotton wool spots actually look soft around the edge
What is the next stage of eye disease after background?
Pre-proliferative
What are the features of pre-proliferative
Cotton wool spots (the hard edges become round and soft)
Features of proliferative eye disease
Neovascularisation
What are cotton wool spots?
The products of ischaemia
Treatment of pre-proliferative
Pan retinal photocoagulation (around the periphery)
How long does it take to see the effect of proper diabetes control? What study published this data and when?
15 years
UKPDS, 1998
What happened 10 years after this study, in 2008? What is the name of the key effect?
The legacy effect - the benefits of having tight control for 20 years extends for nearly 10 years even after the cessation of randomised control!
DCCT
Type 1 diabetes
What did the Accord research show?
This study was done on older people with more than 6% HbA1c with vascular disease
They had
What happens if you suddenly tighten up control in older people with poor control?
It increases their chances of hypos and therefore daeath
What happens if you suddenly tighten up control in older people with poor control?
It increases their chances of hypos and therefore death
Name a sulphonylurea
Gliclazide
Name insulin sensitisers
Pioglitazones
Which drug was banned after the Accord study?
Rosiglitazone
What do you add after insulin sensitisers?
Add insulin
What do you add after insulin?
Incretins e.g. GLP-1
What prevents breakdown of GLP-1?
DPP4 inhibitors
What is the problem with using natural soluble insulin sc?
It forms a hexamer under the skin (A and B chain form parallel links) and releases c-peptide
Took a while to work so had to be injected 30 mins before meals
What did pharmaceutical companies do to reduce the time taken for the insulin to work?
Lispro - rapidly acting as they switched the lysine and proline
Aspart - lysine removed? (proline and aspartate)
Give an example of long acting insulin
Glargine
Arginine added to B chain
What is the point of giving background long acting insulin?
less risk of hypoglycemia
What is detemir?
Long chain insulin
14 carbon fatty acid chain attached to b29
delayed onset 7hr
can be used as part of bolus
What is the advantage of insulin over other diabetic drugs?
Metformin
Sulphonylurea - skin reactions?
Thiazolidinediones - hepatic, osteoporosis (rare)
What are the disadvantages of insulin?
Can’t work if you drive a HGV as hypoglycemia is common
Weight gain (as it makes you more hungry)
What is GLP1?
Secreted from gut, stimulates pancreas to make insulin
What is another advantage of GLP1?
Reduces gastric emptying (feel more full)
What ending do DPP4 inhibitors have?
Gliptins (DPP4 inhibitors)
Give examples of GLP1 analogues
Exanatide
Liraglutide (Saxenda)
How do SGLT2 inhibitors work?
Block reabsorption of glucose so increases glucosuria
Main SE of SGLT2 inhibitors?
UTI
Thrush
Example of an SGLT2 inbhibitor?
Empagliflozin
Which study showed how beneficial SGLT2 inhibitors were?
EMPA-REG Outcome study
What is the effect of SGLT2 inhibitors on the kidneys
GFR is acutely changed, but then remains stable, and it maintains renal function
Thus renoprotective
The risk of death increases if someone has
CKD plus diabetes
What histological features are seen on kidney biopsy?
Mesangial expansion
BM thickening
Glomerulosclerosis
What are the features of kidney disease
Increased proteinuria
Increased
BP
Deranged kidney fucntion
Normal range for proteins in urine?
<30mg/24hrs
Microalbuminuria range
30-300mg/34hr
What is nephrotic syndrome?
More than 3g/24hrs
What are the four interventions for kidney contrl
Tight diabetic control
BP control
Inhibit RAS with ACEi/ARB
Start smoking
When do you start treatment on
Once someone has micro albuminuria
Give an example of an ARB
Irbesartan
What is the effect of ACEi on creatinine within days of starting it?
The creatinine gets worse, but it gets better so keep going with it
ACEi should not be used in?
SHOULD NOT BE USED IN RENAL ARTERY STENOSIS
ACEi causes hyper or hypokalemia?
hyperkalemia
???
Less albuminuria
Less GFR
SE of metformin
Diarrhoea
Tummy ache
When do you try a second oral agent after metformin?
If the non-insulin monotherapy does not achieve the target HbA1C after 3 months
What is the second line for diabetes after metformin?
GLP-1 receptor agonist (e.g. liraglutide) or basal insulin
A network meta analysis shows that which drugs should you give if someone has atherosclerosis/vascular disease, AND diabetes?
Empagliflozin
Liraglutide
What are the glutides?
GLP-1 agonists (incretins, increase
SE of SGLT-2 inhibitors
Increased risk of genital skin reactions
If you need to minimise hypoglycaemia, what do you do?
DDP4?
Gliclazide should be given when
If the pt is overweight?
