🧪Endocrinology🧪 - Micro/Macrovascular Complications of Diabetes Flashcards
What are the 2 types of vascular complications you can get from DM?
Microvascular
Macrovascular
What are the microvascular complications of DM?
Retinopathy
Nephropathy
Neuropathy
What are the macrovascular complications of DM?
Cerebrovascular disease
Ischaemic heart disease
Peripheral vascular disease
What is the association between extent of hyperglycaemia and microvascular complications?
Extent/severity of hyperglycaemia (measured by HbA1c) is strongly associated with increased risk of microvascular complications
What is the target HbA1c to reduce the risk of microvascular complications?
53 mmol/mol (<7%)
What is the relationship between hypertension and complication risk?
Rise of systolic BP leads to increase in risk of microvascular complications and myocardial infarction
What are the other factors related to the development of microvascular complications?
Duration of diabetes
Smoking - endothelial dysfunction
Genetic factors
Hyperlipidaemia
Hyperglycaemic memory
What is meant by hyperglycaemic memory in the context of microvascular complications?
Inadequate glucose control early on can result in higher risk of complications LATER, even if HbA1c improved - some damage is already done
What is the overall mechanism of vascular damage in DM?
Activation of inflammatory pathways
Damaged endothelium results in:
-‘Leaky’ capillaries
-Ischaemia
(diagram is for context - not memorisation)
What is diabetic retinopathy a problem?
Leading cause of:
-Visual loss in people with diabetes
-Blindness in people of working age
Why does diabetic retinopathy need to be screened for?
Early stages are asymptomatic
Aim of screening - to detect retinopathy EARLY when it can be treated before it causes visual disturbance / loss
Annual retinal screening in the UK for all diabetes patients
What are the 4 types of diabetic retinopathy that will be experienced, from least to most severe?
Background retinopathy
Pre-proliferative retinopathy
Proliferative retinopathy
Diabetic maculopathy
What causes diabetic retinopathy?
High blood sugar damages retinal vessels, causing leakage and ischemia.
Neovascularization occurs as the retina tries to compensate, but these new vessels are fragile and may rupture
Leakage and ischaemia, compounded with new fragile vessels, disrupt retinal function
What is background retinopathy?
Leaks of fluids/lipids disrupts retinal function
No new vessel formation (can progress)
Hard exudates, microaneurysms, blot haemorrhages
What is pre-proliferative retinopathy?
Intermediate stage of diabetic retinopathy
Multiple retinal haemorrhages,** venous abnormalities** (such as beading and looping), and areas of ischemia
These changes signal worsening retinal damage and increased risk of progression to proliferative retinopathy, where abnormal blood vessel growth (neovascularization) can occur, leading to severe vision loss if untreated
What is proliferative retinopathy?
Ischaemic damage to retina due to lack of endothelial integrity has lead to neovascularisation
Major retinal disruption
Progression of background retinopathy -> pre-proliferative -> proliferative retinopathy
What is maculopathy?
Same as retinopathy, but happens to be near the macula
Much more serious threat to macular vision
What is the treatment plan for all retinopathies?
Improve HbA1c, stop smoking, lipid lowering
Achieve good BP control (<130/80mmHg)
What is the treatment plan for background retinopathy?
Continued annual surveillance
What is the treatment plan for pre-proliferative retinopathy?
If left alone will progress to new vessel growth
So, early panretinal photocoagulation
What is the treatment plan for proliferative retinopathy?
Panretinal photocoagulation
What is the treatment plan for diabetic maculopathy?
Oedema: Anti-VEGF injections directly into the eye (VEGF: vascular endothelial growth factor)
Grid photocoagulation
What is photocoagulation?
Burning of blood vessels using a high power laser
Prevent proliferation of blood vessels
What is an adverse effect of photocoagulation?
Loss of vision in the target retina
Why is diabetic nephropathy clinically important?
Associated with progression to end stage renal failure - haemodialysis needed
Healthcare burden
Associated with increased risk of cardiovascular events
What is microalbuminuria and what is it’s significance?
Small amount of albumin in urine
Early sign of kidney damage in nephropathy
What is the ACR?
Albumin to creatinine ratio
Why is the ACR useful?
It gives a ratio, so accounts for changes in urine concentration and GFR
More albumin could mean further kidney damage or just a higher rate of filtration, so ACR accounts for this
More reliable assessment of kidney damage
What is the threshold for proteinuria in terms of ACR?
ACR>30mg/mmol
What is the significance of proteinuria exceeding 3000mg/24hr?
Significant level of proteinuria from severe damage to glomeruli
Nephrotic syndrome
What is the next step for a patient with a UACR indicative of proteinuria?
Repeat the test
False positives are quite common
Causes include, fever, urine infection etc…
Outline the mechanism of diabetic nephropathy
What system is a key target for drugs aiming to help treat diabetic nephropathy?
Renin-angiotensin system (RAS)
What are the 2 types of drugs that can block the RAS?
ACE inhibitors (ACEi) - inhibits production of angiotensin 2
Angiotensin receptor blockers (ARBs) - prevents binding of angiotensin 2 to its receptors
What is the suffix for ACE inhibitors?
-pril
What is the suffix for ARBs?
-sartan
Why is there no benefit to using ACEi/ARBs in combination?
ACEi prevents production of A2, therefore ARBs not needed and not affected
What should a diabetes patient with microalbuminuria/proteinuria be given if they are normotensive?
Still give ACEi/ARBs
Why is the correlation between microalbuminuria and cardiovascular disease?
Strong correlation
Strong ties to microalbuminuria being a risk factor
What is the management plan for a patient with diabetic nephropathy?
Aim for optimal glycaemic control (HbA1c <53 mmol/mol)
ACEi/ARB even if normotensive as soon as patient has microalbuminuria
Reduce BP (aim <130/80 mmHg) usually through ACEi or A2RB
Stop smoking
Start an SGLT-2 inhibitor if T2DM (reduces risk of progression of chronic kidney disease)
How does diabetic neuropathy arise?
Small vessels supplying nerves are called vasa nervorum
Neuropathy results when vasa nervorum get blocked
What are the risk factors for diabetic neuropathy?
Age
Duration of diabetes
Poor glycaemic control
Height (longer nerves in lower limbs of tall people)
Smoking
Presence of diabetic retinopathy
How does diabetic neuropathy present?
Longest nerves supply feet – so more common in feet
Commonly glove & stocking distribution – peripheral neuropathy
Can be painful
Danger is that patients will not sense an injury to the foot (e.g. stepping on a nail)
What is a major concern with diabetic neuropathy that requires screening?
Diabetic foot ulceration (also foot injury in general)
How is diabetic foot ulceration avoided and describe the check
All people with diabetes: annual foot check
Look for foot deformity, ulceration
Assess sensation (monofilament, ankle jerks)
Assess foot pulses to assess circulation (dorsalis pedis and posterior tibial)
How does diabetic neuropathy lead to foot ulcerations?
Reduced sensation to feet (peripheral neuropathy)
Poor vascular supply to feet (peripheral vascular disease)
What is the management of diabetic foot disease if affected by peripheral neuropathy?
Regular inspection of feet by affected individual
Good footwear
Avoid barefoot walking
Podiatry and chiropody if needed
What is the management of diabetic foot disease if affected by peripheral neuropathy with ulceration?
Multidisciplinary diabetes foot clinic
Offloading
Revascularisation if concomitant PVD
Antibiotics if infected
Orthotic footwear
Amputation if all else fails
What other neuropathies can occur due to diabetic neuropathy?
Mononeuropathy
Usually, sudden motor loss
eg wrist drop, foot drop
Cranial nerve palsy
double vision due to 3rd (oculomotor) nerve palsy
Autonomic neuropathy
What are the implications of autonomic neuropathy?
Damage to sympathetic and parasympathetic nerves innervating GI tract, bladder, cardiovascular system
GI tract
Delayed gastric emptying: nausea
and vomiting (can make prandial short-acting insulin challenging)
Constipation / nocturnal diarrhoea
Cardiovascular
Postural hypotension: can be disabling - collapsing on standing
Cardiac autonomic supply: sudden cardiac death
How are macrovascular diseases managed/prevented?
Aggressive management of multiple risk factors
What are the modifiable risk factors for macrovascular complications (therefore can be targeted with the goal of prevention)?
Dyslipidaemia
Hypertension
Smoking
Diabetes Mellitus
Central obesity
What are the non-modifiable risk factors for macrovascular disease?
Age
Sex
Birthweight
FH/Genes
What are the steps for managing cardiovascular risk in diabetes mellitus?
Smoking status – support to quit
Blood pressure - <130/80 mmHg if microvascular complication or increased metabolic risk (NB often needs multiple agents)
Lipid profile – total cholesterol <4, LDL <2
Weight – discuss lifestyle intervention +/- pharmacological treatments
Annual urine microalbuminuria screen – risk factor for cardiovascular disease
