Microvascular and Macrovascular complications Flashcards
What are examples of microvascular complications
Retinopathy
Nephropathy
Neuropathy
What are examples of macrovascular complications
Cerebrovascular disease
Ischaemic heart disease
Peripheral vascular disease
Explain the relationship of risk with rising HbA1c
Extent of hyperglycaemia (as judged by HbA1c) is strongly associated with the risk of developing microvascular complications
Target HbA1c to reduce risk of microvascular complications
= 53 mmol/mol (<7%)
How does hypertension increase complication risk
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 factors are related to the development of microvascular complications
Duration of diabetes
Smoking – endothelial dysfunction
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
Describe the mechanism of damage
Increased formation of mitochondrial superoxide free radicals in the endothelium
Generation of glycated plasma proteins to form advanced glycation end products (AGEs)
Activation of inflammatory pathways
Damaged endothelium results in
‘Leaky’ capillaries
Ischaemia
Explain diabetic retinopathy
Main cause of
-visual loss in people with diabetes
-blindness in people of working age
The early stages of retinopathy are all asymptomatic, therefore screening is needed
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 does a normal retina look like?
Optic disk (Bright white)
Macula - central, high resolution, colour vision (darker yellow)
What is background retinopathy?
Haemorrhages
Microaneurysms - red dots
Hard exudates (cheese colour, lipid)
Endothelial damage, leaking blood vessels
What is pre-proliferative retinopathy
Cotton wool spots aka Soft exudates, Represent retinal ischaemia
Haemorrhage
What is proliferative retinopathy
Visible new vessels
On disc or elsewhere in retina
What is maculopathy
Hard exudates / oedema near the macula
Same disease as background, but happens to be near macula
This can threaten vision
How do you treat retinopathy and maculopathy?
Improve HbA1c, stop smoking, lipid lowering
good blood pressure control <130/80 mmHg
What to do for background retinopathy?
Continued annual surveillance
What to do for pre-proliferative retinopathy
If left alone will progress to new vessel growth
So, early panretinal photocoagulation
What to do for proliferative retinopathy
Panretinal photocoagulation
What to do for diabetic maculopathy
Oedema: Anti-VEGF injections directly into the eye (VEGF: vascular endothelial growth factor)
Grid photocoagulation
Why is diabetic nephropathy important
Associated with progression to end-stage renal failure requiring haemodialysis
Healthcare burden
Associated with increased risk of cardiovascular events
What is pan-retinal photocoagulation?
Blast vessels with laser to stop them form bleeding or forming
Reduces peripheral vision
How to diagnose diabetic nephropathy?
Progressive proteinuria (urine albumin:creatinine ratio - ACR)
Increased blood pressure
Deranged renal function (eGFR)
Advanced: peripheral oedema
What test results indicate diabetic nephropathy
Microalbuminuria
>2.5 mg/mmol = early sign
Proteinuria = ACR > 30mg/mmol
Nephrotic Range > 3000mg/24hr
What is the mechanism of diabetic nephropathy
Diabetes leads to hyperglycaemia / hypertension
This leads to glomerular hypertension
Leads to proteinuria
Leads to glomerular and interstitial fluids
Leads to glomerular filtration rate decline
Leads to renal failure
Describe the renin-angiotensin system
Renin from the kidney converts angiotensinogen to angiotensin I
ACE converts angiotensin I to angiotensin II
Angiotensin II promotes release of aldosterone from adrenal cortex (zona glomerulosa) and vasoconstrictor
Very active in those with diabetic nephropathy
Angiotensin II acts via angiotensin receptors
ACE inhibitors (ACEi) are antihypertensives which block ACE
Angiotensin receptor blockers (ARBs) are antihypertensives which block angiotensin receptors
Blocking RAS with an ACE inhibitor (‘-pril) or angiotensin 2 receptor blocker (ARB, ‘-sartan’) reduces blood pressure & progression of diabetic nephropathy
All diabetes patients with microalbuminuria/proteinuria should have an ACEi/ARB even if normotensive
No benefit to having both ACEi/ARB simultaneously
What is microalbuminuria a risk factor for?
Cardiovascular disease
How to manage diabetic nephropathy
Aim for tighter glycaemic control
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?
What is diabetic neuropathy
Diabetes mellitus 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
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 (eg. stepping on a nail)
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
Why do patients with diabetes needs an annual foot check
- Look for foot deformity, ulceration
- Assess sensation (monofilament, ankle jerks)
- Assess foot pulses (dorsalis pedis and posterior tibial)
Which patients are more at risk of foot ulceration
- reduced sensation to feet (peripheral neuropathy)
- poor vascular supply to feet (peripheral vascular disease)
How to manage diabetic food disease
Peripheral neuropathy
1. Regular inspection of feet by affected individual
2. Good footwear
3. Avoid barefoot walking
Podiatry and chiropody if needed
Peripheral neuropathy with ulceration:
Multidisciplinary diabetes foot clinic
Offloading
Revascularisation if concomitant PVD
Antibiotics if infected
Orthotic footwear
Amputation if all else fails
What is a mononeuropathy
Usually, sudden motor loss
eg wrist drop, foot drop
Cranial nerve palsy
double vision due to 3rd (oculomotor) nerve palsy
3rd nerve palsy
Eye looks DOWN & OUT
What is autonomic neuropathy and what do patients present with?
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
What are the non modifiable risk factors for macrovascular disease
Age
Sex
Birth weight
FH/Genes
What are the modifiable risk factors for macrovascular disease
Dyslipidaemia
Hypertension
Smoking
Diabetes mellitus
Central obesity
How to manage cardiovascular risk in Dm
Smoking status – support to quit
Blood pressure < 140/80 mmHg, < 130/80 mmHg if microvascular complication (NB often needs multiple agents)
Lipid profile – total chol <4, LDL <2
Weight – discuss lifestyle intervention +/- pharmacological treatments
Annual urine microalbuminuria screen – risk factor for cardiovascular disease
