Micro and Macrovascular Flashcards
Microvascular complication
Retinopathy
Nephropathy
Neuropathy
Macrovascular complications
Cerebrovascular disease
Ischaemic heart disease
Peripheral vascular disease
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
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%)
Hypertension also increases 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
Other factors 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
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
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
Retinopathy
Background retinopathy
Pre-proliferative retinopathy
Proliferative retinopathy
Maculopathy
Background retinopathy
Hard exudates (cheese colour, lipid) Microaneurysms (“dots”) Blot haemorrhages
Pre-proliferative retinopathy
Cotton wool spots also called soft exudates
Represent retinal ischaemia
Proliferative retinopathy
Visible new vessels
On disc or elsewhere in retina
Maculopathy
Hard exudates / oedema near the macula
Same disease as background, but happens to be near macula
This can threaten vision
Treatment of retinopathy & maculopathy
Continued annual surveillance
If left alone will progress to new vessel growth
So, early panretinal photocoagulation
Panretinal photocoagulation
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
Diagnosis of nephropathy
Progressive proteinuria (urine albumin:creatinine ratio - ACR)
Increased blood pressure
Deranged renal function (eGFR)
Advanced: peripheral oedema
Microalbuminuria
>2.5 mg/mmol
Proteinuria = ACR > 30mg/mmol
Nephrotic Range > 3000mg/24hr
Mechanism of diabetic nephropathy
Hyperglycaemia and hypertension
Lead to glomerular hypertension
Proteinuria
Glomerular and interstitial fibrosis
Glomerular filtration rate decline
Renal failure
Renin-Angiotensin System (RAS)
Angiotensin II acts via angiotensin receptors
ACE inhibitors (ACEi) are antihypertensives which block ACE
Angiotensin receptor blockers (ARBs) are antihypertensives which block angiotensin receptors
Diabetic nephropathy & RAS
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
Management of 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?
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
Risk factors include
- Age - Duration of diabetes - Poor glycaemic control - Height (longer nerves in lower limbs of tall people) - Smoking - Presence of diabetic retinopathy
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)
Diabetic foot ulceration
All people with diabetes: annual foot check
- Look for foot deformity, ulceration - Assess sensation (monofilament, ankle jerks) - Assess foot pulses (dorsalis pedis and posterior tibial)
Risk of foot ulceration in patients with
- reduced sensation to feet (peripheral neuropathy) - poor vascular supply to feet (peripheral vascular disease)
Management of diabetic foot 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
Other neuropathies
Mononeuropathy Usually, sudden motor loss eg wrist drop, foot drop Cranial nerve palsy double vision due to 3rd (oculomotor) nerve palsy
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
Risk factors for macrovascular disease
Non-modifiable Age Sex Birth weight FH/Genes
Modifiable Dyslipidaemia Hypertension Smoking Diabetes mellitus Central obesity
Managing cardiovascular risk in diabetes mellitus
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
