1B microvascular and macrovascular complications Flashcards
What are the microvascular complications of DM?
Small vessel complications
- Retinopathy- damage to retina
- Nephropathy- damage to kidney
- Neuropathy- damage to nerves
What is the risk of developing microvascular complications strongly associated with?
The extent of hyperglycaemia (judged by HbA1c)
What is the target HbA1c to reduce risk of microvascular complications?
53 mmol/mol (<7%)
What other big risk factor increases risk of microvascular complications?
Hypertension
- There’s a clear relationship between rising systolic BP and risk of MI and microvascular complications in DM patients
- Therefore, prevention of complications requires reduction in HbA1c and BP control
What are a list of other risk factors related to development of microvascular complications?
- Duration of diabetes
- Smoking- endothelial dysfunction
- Genetic factors- some people develop complications despite reasonable glycaemic control
- Hyperlipidaeima
- Hyperglycaemic memory- inadequate glucose control early on can result in higher risk of complications LATER, even if HbA1c improved
What is the mechanism of damage to microvascular system by DM?
- Increased formation of mitochondrial superoxide free radicals in endothelium (oxidative stress)
- generation of glycated plasma proteins to form advanced glycation end products (AGEs)
- Hypoxia
- Whichever of the above 3 mechanisms happens, it leads to activation of inflammatory pathways
What does damage of endothelium result in in microvascular system?
- Leaky capillaries- blood and blood products leak out of capillaries
- Ischaemia- endothelium can’t transport blood properly to tissues
What is diabetic retinopathy the main cause of?
- Visual loss in people with diabetes
- Blindness in people of working age
Why is yearly retinal screening of DM patients needed?
- Early stages of retinopathy are asymptomatic
- The aim of screening is to detect retinopathy early when it can be treated before it causes visual disturbance/loss
What does a normal retina look like?
Macula in middle, optic disk on side
What does background retinopathy look like (name features)?
- Hard exudates (cheese colour)- lipids leaked out because endothelium is dysfunctional
- Microaneurysms (dots)
- Blot haemorrhages because vessels are more leaky
What does pre-proliferative retinopathy look like (name features)?
Cotton wool spots aka soft exudates- these represent retinal ischaemia
What does proliferative retinopathy look like (name features)?
- Visible new vessels on disc or elsewhere in retina
- New vessels have developed because of hypoxia to try to get more blood to ischaemic retina
- These vessels are very friable and easy to damage and bleed- bad news to see
- If they’re by the macula, that’s not good
What does maculopathy look like (name features)?
- Hard exudates (from leaky capillaries)/oedema near macula
- Same disease as background but happens to be near macula
- This can threaten vision
What is the treatment for background retinopathy?
Continued annual surveillance
What is the treatment for pre-proliferative retinopathy?
If left alone will progress to new vessel growth, so early panretinal photocoagulation is given.
What is early panretinal photocoagulation?
You burn through retina with a laser through area of new vessel formation or extensive haemorrhage to stop there being more damage
This does impact patient’s peripheral vision
What treatment is given to proliferative retinopathy?
Panretinal photocoagulation
What treatment is given to diabetic maculopathy?
- Oedema → anti-VEGF injections directly into the eye (VEGF- vascular endothelial growth factor)
- Grid photocoagulation
What 2 things do we need make sure we improve throughout in retinopathy?
- Improve HbA1c, stop smoking, lipid lowering
- Good bp control <130/80 mmHg
Why is diabetic nephropathy important?
- Associated with progression to end-stage renal failure requiring haemodialysis
- Healthcare burden
- Associated with increased risk of cardiovascular disease (big cause of death in DM patients)
How do we diagnose diabetic nephropathy?
- Progressive proteinuria (measure urine albumin:creatinine ratio aka ACR)
- Deranged renal function (eGFR)
- Increased blood pressure
- Advanced- peripheral oedema because of deranged fluid balance
What are the different levels of ACR in the blood called in terms of disease?
- Microalbuminuria is >2.5 mg/mmol → this is the earliest hallmark of diabetic kidney disease
- Proteinuria is >30 mg/mmol
- Nephrotic range is when you lose >3000mg/24hr
What is the mechanism of diabetic nephropathy?
- Diabetes leads to hyperglycaemia and hypertension
- This leads to glomerular hypertension (hyperglycaemia would contribute through inflammation)
- Leads to proteinuria → causes glomerular and interstitial fibrosis → leading to GFR decline → leading to renal failure
How does the renin-angiotensin system (RAS) work?
- Angiotensinogen converted by renin from JGA of kidney into angiotensin I
- ACE converts angiotensin I into angiotensin II
- Angiotensin II acts via angiotensin receptors- causing vasoconstriction and release of aldosterone from adrenal cortex (both lead to hypertension)
How do ACE inhibitors and angiotensin receptor blockers work?
- ACE inhibitors (ACEi) are antihypertensives that block ACE
- Angiotensin receptor blockers (ARBs) are antihypertensives which block angiotensin receptors
What should you give to someone as soon as you notice they’re developing kidney disease e.g. through microalbuminuria?
- Put them on an ACEi or ARB even if they’re normotensive- this reduces blood pressure and progression of diabetic nephropathy
- ACE inhibitors end in ‘pril’ and ARB end in ‘sartan’
Is there any benefit to having both ACEi/ARB simultaneously?
No- there’s no benefit of having both and actually they can cause some potassium problems
What type of diseases is microalbuminuria a risk factor for?
Cardiovascular disease like ischaemic stroke and MI
What is the management of diabetic nephropathy?
Decrease risk of CVD by:
- Aim for tighter glycaemic control so endothelial remains healthier
- ACEi/ARB even if normotensive as soon as patient has microalbuminuria
- Reduce BP (aim for <130/80 mmHg) usually through ACEi or ARB
- Stop smoking
- Start an SGLT-2 inhibitor if T2DM- some evidence that suggests it helps
How is diabetic neuropathy caused?
- DM is most common cause of neuropathy and therefore lower limb amputation
- Small vessels supplying nerves are called vasa nervorum
- Neuropathy results when vasa nervorum get blocked
What do risk factors of diabetic neuropathy include?
- Age
- Duration of diabetes (longer you’ve had diabetes, the more exposure to hyperglycaemia you’ve had)
- Poor glycaemic control
- Height (longer nerves in lower limbs of tall people)
- Smoking
- Presence of diabetic retinopathy- if you already have had microvascular damage, you may have it elsewhere
What is the common distribution of diabetic neuropathy?
- Longest nerves supply feet- so more common in feet
- Commonly glove and stocking distribution- peripheral neuropathy
What is the issue of diabetic neuropathy?
- Can be painful
- Danger is that patients won’t sense an injury to the foot (e.g. stepping on a nail)
How do we assess for diabetic foot ulceration?
All diabetes patients should have annual foot check:
- Look for foot deformity, ulceration
- Assess sensation using monofilament and also ankle jerks
- Assess foot pulses (dorsalis pedis and posterior tibial)
What patients have a risk of foot ulceration?
- reduced sensation to feet (peripheral neuropathy)- can’t detect when foot is wounded
- Poor vascular supply to feet (peripheral vascular disease)- wound can’t heal
How do we manage diabetic foot disease for peripheral neuropathy?
- Regular inspection of feet by affected individual
- Good footwear
- Avoid barefoot walking
- Podiatry and chiropody if needed
How do we manage diabetic foot disease for peripheral neuropathy with ulceration?
- Multidisciplinary diabetes foot clinic
- Offloading
- Revascularisation if concomitant PVD (peripheral vascular disease)
- Antibiotics if infected
- Orthotic footwear
- Amputation if all else fails
What is mononeuropathy?
- Usually, sudden motor loss e.g. wrist drop, foot drop
- Cranial nerve palsy, double vision due to 3rd (oculomotor) nerve palsy
What is autonomic neuropathy?
Damage due to DM to sympathetic and parasympathetic nerves innervating GI tract, bladder, cardiovascular system
What is the effects of mononeuropathy on the GI tract?
- Delayed gastric emptying- nausea and vomiting (can make prandial short-acting insulin challenging)
- Constipation/nocturnal diarrhoea
What is the effects of autonomic neuropathy on the cardiovascular system?
- postural hypotension- can be disabling- collapsing on standing
- Cardiac autonomic supply- sudden cardiac death since heart just stops beating
What are the macrovascular complications of DM?
large vessel complications
- Cerebrovascular disease- stroke
- Ischaemic heart disease
- Peripheral vascular disease- usually happens to foot
Why is it important for us to look out for these complications?
- Treatment targeted to hyperglycaemia alone has minor effect in combating increased risk of CVD
- Prevention of macrovascular disease requires aggressive management of multiple risk factors
What non-modifiable risk factors are there for macrovascular disease? (
- Age
- Sex
- Birth weight
- FH (familial hypercholesterolaemia)/genes
What modifiable risk factors are there for macrovascular disease?
- Dyslipidaemia (abnormal lipid levels in body)
- Hypertension
- Smoking
- DM
- Central obesity
How do we manage cardiovascular risk in DM for smoking status?
Support to quit
How do we manage cardiovascular risk in DM for BP?
- Aim for <140/80 mmHg but <130/80 mmHg if microvascular complication
- Often needs multiple agents- try ARB or ACEi as first line but then add more agents as needed
How do we manage cardiovascular risk in DM for lipid profile?
Treat dyslipidaemia with HMG-CoA reductase inhibitors/bile-acid binding resins
- Total chol <4
- LDL <2
How do we manage cardiovascular risk in DM for weight?
Discuss lifestyle intervention with or without pharmacological treatments
How do we manage cardiovascular risk in DM for annual urine microalbuminuria screen?
Risk factor for CVD
