Micro- and Macro-vascular Complications of Diabetes Mellitus Flashcards
What are examples of microvascular complications of DM?
- retinopathy
- nephropathy
- neuropathy
What are examples macrovascular complications of DM?
- Cerebrovascular disease
- Ischaemic heart disease
- Peripheral vascular disease
What is strongly associated with the risk of developing microvascular complications?
The extent of hyperglycaemia
What is the target HbA1c to reduce the risk of microvascular complications?
53mmol/mol (<7%)
What is the relationship between rising systolic BP and risk of MI and microvascular complication in people T1DM and T2DM?
- positive relationship
- high BP leads to higher risk of MI and microvascular complications in those with T1DM and T2DM
What is required for the prevention of complications of DM?
reduction in:
- HbA1c
- BP (should be controlled)
What are the factors associated with the development of microvascular complications?
- duration of diabetes
- smoking (endothelial dysfunction)
- genetic factors (development irrelevant of glycaemic control)
- hyperlipidaemia
- hyperglycaemic memory
What is hyperglycaemic memory?
inadequate glucose control early on > high risk of later complications (even if HbA1c improves)
What is the general mechanism of damage involved in microvascular complications?
- increased formation of mitochondrial superoxide free radicals in the endothelium
- generation of glycated plasma proteins to form advanced glycation end products (AGEs)
- Activation of Inflammation pathways
- Damaged endothelium leads to: ‘leaky’ capillaries and Ischaemia
What does hyperglycaemia and hyperlipidemia trigger?
- AGE-RAGE
- Oxidative stress
- Hypoxia
What does AGE-RAGE, Oxidative stress and Hypoxia trigger?
- Inflammatory Signalling Cascade
- Local activation of pro-inflammatory cytokines
- Inflammation
How prevalent is Diabetic Retinopathy?
main cause of:
- visual loss in people with diabetes
- blindness in people of working age
Why is Diabetic Retinopathy screening
needed?
- early stages are asymptomatic
What is the aim of Diabetic Retinopathy Screening?
- detect it early
- before it causes visual disturbance and loss
How often is Diabetic Retinopathy screening for diabetes patients?
UK - annual screening
What is the visual presentation of Background Retinopathy?
- Hard exudates (cheese colour, lipid)
- Microaneurysms (dots)
- Blot haemorrhages
What is the physical presentation of Pre-Proliferative Retinopathy?
- Soft exudates (cotton wool spots)
- haemorrhage
- representative of retinal ischaemia
What characterises Proliferative Retinopathy?
- visible new vessels
on disk or elsewhere in retina
What is Maculopathy?
- same as background retinopathy but near macula
- hard exudates/oedema near the macula
- threatens vision
What is the Macula?
- central, high resolution, colour vision
What is the optic disc?
- point of origin of the blood vessels of the eye
What is the first treatment plan for all retinopathys and maculopathys?
- improve HbA1c
- smoking cessation
- lipid lowering
- blood pressure control (good, <130/80mmHg)
What further should be used to treat Background Retinopathy?
- continued annual surveillance
What further should be done to treat Pre-proliferative Retinopathy?
- if left alone, will lead to new vessel growth
- Early Panretinal Photocoagulation
What further should be done to treat Proliferative Retinopathy?
-Panretinal photocoagulation
What can be done to further treat Diabetic Maculopathy?
- Oedema: Anti-VEGF (Vascular Endothelial Growth Factor) injections directly into the eye
- Grid Photocoagulation
What is Pan-retinal Photocoagulation?
- for: retinal ischemic disease
- creating thermal burns in the peripheral retina leading to tissue coagulation
- improved retinal oxygenation
What is diabetic nephropathy associated with?
- progression to end-stage renal failure requiring haemodialysis
- increased risk of cardiovascular events
How do you diagnose diabetic nephropathy?
- progressive proteinuria (urine albumin:creatinine ratio)
- Increased BP
- Deranged Renal Function (eGFR)
- Advanced: peripheral oedema
What values would you see when diagnosing diabetic nephropathy?
- Microalbuminuria, >2.5mg/mmol
- ACR, >30mg/mmol
- Nephrotic Range, >3000mg/24hr
What is the mechanism of diabetic nephropathy?
- hyperglycemia and hypertension
- glomerular hypertension
- proteinuria
- glomerular and interstitial fibrosis
- glomerular filtration rate decline
- renal failure
Where does Angiotensin II act?
via angiotensin receptors
What do ACE inhibitors do?
- antihypertensives
- block ACE
What do ARBs (Angiotensin Receptor Blockers) do?
- antihypertensives
- block angiotensin receptors
What is the common suffix of ACE inhibitors?
- pril
What is the common suffix of ARBs?
- sartan
What does blocking the Renin-Angiotensin System using ACE/ARB do?
- reduces blood pressure
- slows the progression of diabetic nephropathy
When should diabetes patients have a ACEi/ARB?
- microalbuminuria/proteinuria
- EVEN, if normotensive
When should patients be on both ACEi and ARB?
- never
- no clinical benefit
What is microalbuminuria a risk factor for?
cardiovascular disease
What is involved in the management of diabetic nephropathy?
- tight glycaemic control
- ACE/ARB with microalbuminuria
- reduce BP (<130/80)
- Smoking cessation
- SGLT-2 inhibitor is T2DM?
What is neuropathy?
When vasa nervorum (small vessels supplying nerves) get blocked
What is the most common cause of neuropathy?
- Diabetes Mellitus
most common cause of lower limb amputation
What are the risk factors of neuropathy?
- age
- duration of diabetes
- poor gylcaemic control
- height (longer nerves in lower limbs)
- smoking
- presence of diabetic retinopathy
Where is diabetic neuropathy most common?
- in the feet (longest nerves in the feet)
- most common: glove and stocking distribution (peripheral neuropathy)
What is the danger of diabetic neuropathy?
- can be painful
- not being able to sense an injury to the foot
What is included in the annual foot check (for those with diabetes)?
- foot deformity?
- ulceration?
- sensation? (monofilament, ankle jerks)
- foot pulses? (dorsalis pedis, posterior tibial)
Where is there a risk of foot ulceration?
- reduced foot sensation (peripheral neuropathy)
- poor vascular foot supply
(peripheral vascular disease)
What is involved in the management of peripheral neuropathy?
- regular foot inspection (self)
- good footwear
- avoid barefoot walking
- IF needed: podiatry and chiropody
What is involved in the management of peripheral neuropathy with ulceration?
- multidisciplinary diabetes foot clinic
- offloading
- revascularisation if concomitant PVD
- antibiotics if infected
- orthotic footwear
- LAST RESORT: amputation
What is mononeuropathy?
- sudden motor loss (eg: wrist and foot drop)
- cranial nerve palsy - double vision due to oculomotor nerve palsy
How to visually confirm 3rd (oculomotor) nerve palsy?
eye looks DOWN and OUT
What is autonomic neuropathy?
damage to the sympathetic and parasympathetic nerves innervating: GI tract, bladder and cardiovascular system
What is the impact of autonomic neuropathy on the GI tract?
- delayed gastric emptying: nausea vomiting (problematic for prandial SA insulin)
- constipation
- noturnal diarrhoea
What is the impact of autonomic neuropathy on the cardiovascular system?
- postural hypotension (possibly disabling, collapsing on standing)
- cardiac autonomic supply > sudden cardiac death
What does the treatment/prevention of macro-vascular complications of DM involve?
- treatment aimed at hyperglycaemia has a minor effect on the increased risk of CVD
- prevention of macro-vascular disease requires aggressive, multifactorial management
What are the modifiable risk factors of macro-vascular disease?
- dyslipidaemia
- hypertension
- smoking
- DM
- central obesity
What are the non-modifiable risk factors of macro-vascular disease?
- age
- sex
- birth weight
- Genes
How do you manage cardiovascular risk in DM?
- smoking cessation
- weight loss (lifestyle changes or pharmacological options)
- annual urine microalbuminuria screen
- lipids: total cholesterol <4, LDL <2
- blood pressure, <140/80 or <130/80 with microvascular complications (multiple agents often required)
