3.19 - Microvascular and macrovascular complications of diabetes mellitus Flashcards
What does microvascular mean?
Small vessel complications
What are the microvascular complications of DM? (3)
- retinopathy - damage to retina
- nephropathy - damage to kidneys
- neuropathy - damage to nerves
What does macrovascular mean?
Large vessel complications
What are the macrovascular complications of DM? (3)
- cerebrovascular disease - stroke
- ischaemic heart disease
- peripheral vascular disease - usually foot
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 the risk of microvascular complications?
53 mmol/mol (<7%) or below
What other big risk factor (other than HbA1c) increases the risk of microvascular complications?
- hypertension
- clear relationship between rising systolic BP and risk of MI and microvascular complications in people with T1DM and T2DM
- therefore, prevention of complications requires reduction in HbA1c and BP control
What other risk factors (other than HbA1c and hypertension) are related to the development of microvascular complications? (5)
- duration of diabetes
- smoking - endothelial dysfunction and inflammation of vessels
- genetic factors - some people develop complications despite reasonable glycaemic control
- hyperlipidaemia
- 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 the microvascular system by DM?
- increased formation of mitochondrial superoxide free radicals in the endothelium (oxidative stress)
- generation of glycated plasma proteins to form advanced glycation end products (AGEs) - high lipids and high glucose
- hypoxia
- these three mechanisms cause activation of inflammatory pathways
- damaged endothelium
What does damaged endothelium as a result of the inflammatory pathway activation result in?
DM mechanism of damage
- ‘leaky’ capillaries - blood and blood products leak out of capillaries
- ischaemia - endothelium cannot 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
What are the symptoms of the early stages of retinopathy?
Asymptomatic (therefore screening is needed)
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 (central, high resolution, colour vision) in middle (darker), optic disc on side (bright)
What is the progression of diabetic retinopathy/maculopathy?
- background retinopathy
- pre-proliferative retinopathy
- proliferative retinopathy
- diabetic maculopathy
What are the features of background retinopathy?
- hard exudates (cheese colour dots, lipid) - lipids leaked out due to dysfunctional endothelium
- microaneurysms (red dots)
- blot haemorrhages - vessels more leaky
What are the features of pre-proliferative retinopathy?
- cotton wool spots (larger yellow spots) AKA soft exudates - represent retinal ischaemia
- haemorrhages
What are the features of proliferative retinopathy?
- visible new vessels on disc or elsewhere in retina
- these have developed due to ischaemia and hypoxia to increase blood/oxygen to ischaemic retina
- vessels are very friable and easy to damage/bleed
What are the features of diabetic maculopathy?
- hard exudates/oedema near macula
- same disease as background retinopathy but happens to be near macula
- this can threaten vision
Can also have cotton wool spots
How do we treat background retinopathy?
Continued annual surveillance
How do we treat pre-proliferative retinopathy?
- if left alone will progress to new vessel growth
- so, early panretinal photocoagulation
How do we treat proliferative retinopathy?
Panretinal photocoagulation
How do we treat diabetic maculopathy?
- oedema –> anti-VEGF (vascular endothelial growth factor) injections directly into the eye
- grid photocoagulation
The purpose of grid photocoagulation is to reduce the leakage of fluid from blood vessels in the macula, which contributes to macular edema. By sealing off leaking blood vessels, grid photocoagulation helps to reduce macular swelling and improve or stabilize vision
What is pan-retinal photocoagulation?
- burn through retina with a laser through area of new vessel formation/extensive haemorrhage to stop further damage
- could impact peripheral vision (black dots on retina)
What two things are important in improving throughout to reduce diabetic retinopathy/maculopathy?
- improve HbA1c, stop smoking, lipid-lowering (cholesterol)
- 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 events
Why should every patient with DM have an annual urine sample?
To quantify the urine albumin:creatinine ratio - ACR
What are the different levels of ACRs called (in terms of disease)?
- microalbuminuria >3mg/mmol (earliest feature of diabetic nephropathy)
- proteinuria > 30mg/mmol
- nephrotic range is when you lose >3000mg/24hr
What needs to be taken into consideration when using urine ACRs to diagnose microalbuminuria?
- false positive results are quite common for urine ACR e.g. fever, urine infection
- a positive urine ACR needs to be repeated to confirm microalbuminuria
What is the mechanism for diabetic nephropathy?
(Don’t need to know)
- diabetes –> hyperglycaemia + hypertension
- these lead to glomerular hypertension (hyperglycaemia contributes through inflammation)
- glomerular hypertension –> proteinuria –> glomerular and interstitial fibrosis –> GFR decline –> renal failure
How does the renin-angiotensin system (RAS) work?
- angiotensinogen (precursor from liver) is 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 (ARBs) work?
- ACE inhibitors are antihypertensives that block ACE
- ARBs are antihypertensives which block angiotensin receptors
How are ACEi/ARBs used in diabetic nephropathy?
- blocking RAS with an ACE inhibitor (‘-pril’) or ARB (‘-sartan’) reduces blood pressure and progression of diabetic nephropathy
- all diabetes patients with microalbuminuria/proteinuria should have ACEi/ARB even if normotensive
- no benefit to having both ACEi/ARB simultaneously
What type of diseases is microalbuminuria a risk factor for?
Cardiovascular disease e.g. ischaemic stroke or MI
How do you manage diabetic nephropathy?
- aim for good glycaemic control (HbA1c <53 mmol/mol)
- ACEi/ARB even if normotensive as soon as patient has microalbuminuria
- reduce BP (aim <130/80mmHg) usually through ACEi/ARB
- stop smoking
- start an SGLT-2 inhibitor if T2DM?
How is diabetic neuropathy caused?
- DM is the 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 are the risk factors of diabetic neuropathy? (6)
- age
- duration of diabetes
- poor glycaemic control
- height (longer nerves in lower limbs of tall people)
- smoking
- presence of diabetic retinopathy (if you have already 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 with diabetic neuropathy?
- can be painful
- danger is that patients will not sense an injury to the foot (e.g. stepping on a nail) = injury not looked after
How do we assess for diabetic foot ulceration?
- all people with diabetes should have annual foot check:
- look for foot deformity, ulceration
- assess sensation using monofilament and ankle jerks
- assess foot pulses (dorsalis pedis and posterior tibial)
What patients have a risk of foot ulceration?
- reduced sensation to feet (peripheral neuropathy) - cannot detect when wounded
- poor vascular supply to feet (peripheral vascular disease) - wound cannot heal
How do we manage diabetic foot disease for peripheral neuropathy? (4)
- 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? (6)
- multidisciplinary diabetes foot clinic
- offloading
- revascularisation if concomitant 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 oculomotor nerve palsy (eye looks down and out due to unopposed SO and LR which are not innervated by CN III)
What is autonomic neuropathy?
Damage to sympathetic and parasympathetic nerves innervating GI tract, bladder, cardiovascular system
What are the effects of autonomic neuropathy on the GI tract?
- delayed gastric emptying - nausea and vomiting (can make prandial short-acting insulin challenging)
- constipation/nocturnal diarrhoea
What are 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 three macrovascular complications of DM?
- cerebrovascular disease
- ischaemic heart disease
- peripheral vascular disease
Why is it important for us to look out for these macrovascular complications?
- treatment targeted to hyperglycaemia alone has minor effect on increased risk of cardiovascular disease
- prevention of macrovascular disease requires aggressive management of multiple risk factors
What are non-modifiable risk factors for macrovascular disease? (4)
- age
- sex
- birth weight
- familial hypercholesterolaemia / genes
What are modifiable risk factors for macrovascular disease? (5)
- dyslipidaemia
- hypertension
- smoking
- diabetes mellitus
- 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 blood pressure?
Aim for <130/80 mmHg if microvascular complication or increased metabolic risk (often needs multiple agents ACEi/ARB and others)
How do we manage cardiovascular risk in DM for lipid profile?
Total cholesterol <4, LDL <2
How do we manage cardiovascular risk in DM for weight?
Discuss lifestyle intervention +/- pharmacological treatments
Why do we do an annual urine microalbuminuria screen in patients with DM?
In relation to cardiovascular risk
Risk factor for CVD
