Microvascular & Macrovascular complications of diabetes mellitus Flashcards
Define microvascular complications and give examples
Complications of smaller vessels
e.g:
Retinopathy
Nephropathy
Neuropathy
Define macrovascular complications and give examples
Complications of larger vessels
e.g:
Cerebrovascular disease
Ischaemic heart disease
Peripheral vascular disease
What is the relationship b/t glucose levels and microvascular complications?
- Extent of hyperglycaemia (as judged by HbA1c) is strongly associated with the risk of developing microvascular complications
What is the normal levels of HbA1c?
48 mmol/mol (6.5%) or below (anything above that is diabetes)
(need to target HbA1c to reduce risk of microvascular complications)
What is the relationship b/t systolic bp and microvascular complication?
- Clear relationship between rising systolic BP (hypertension) and risk of MI and microvascular complications in people with T1DM and T2DM
- Therefore, prevention of complications requires reduction in HbA1c and BP control
(not just management of sugars- need to check BP, cholesterol, etc)
What factors increase your risk of the development of microvascular complications
- HbA1c
- Hypertension
- Duration of diabetes (cannot be altered/ changed)
- Smoking – endothelial dysfunction (damages lining of blood vessels)
- Genetic factors – some people develop complications despite reasonable glycaemic control
- Hyperlipidaemia (can be modified with medication)
- Hyperglycaemic memory – inadequate glucose control early on (e.g. having T1DM at young age) can result in higher risk of complications LATER, even if HbA1c improved
Describe the mechanism of damage to the endothelium
- Hyperglycaemia and hyperlipidemia can result in:
- Hypoxia
- Increased formation of mitochondrial superoxide free radicals in the endothelium (oxidative stress)
- Generation of glycated plasma proteins to form advanced glycation end products (AGEs): the more sugar= more AGEs you have - All 3 of these lead to activation of inflammatory pathways (pro- inflammatory cytokines)
- Damaged endothelium results in:
‘Leaky’ capillaries
Ischaemia
(= Nephropathy, Retinopathy, Neuropathy)
What is diabetic retinopathy?
- Over time, too much sugar in your blood can lead to the blockage of the tiny blood vessels that nourish the retina
- cutting off its blood supply
- As a result, the eye attempts to grow new blood vessels
- But these new blood vessels don’t develop properly and can leak easily.
What would you find on a normal retina scan?
- Optic disc (bright white spot) the area where specific nerve fibres exit the retina to form the optic nerve
- Macula (slightly pink- found centrally) the part responsible for central and fine-detail vision, high resolution and colour vision needed for tasks such as reading.
What is background retinopathy? What would you see on an OCT?
- Earliest stage of retinopathy (no new blood vessels formed yet)
- The walls of the blood vessels in your retina weaken
- Tiny bulges protrude from the walls of the smaller vessels, sometimes leaking fluid and slight blood into the retina
- don’t usually affect your vision – this is known as background retinopathy
OCT: - Hard exudates (yellow bright spots with well defined edges= lipid residues that leak from the impaired blood–retinal barrier)
- Microaneurysms (dots)
- Blot haemorrhages (red dots)
What is Pre-proliferative retinopathy? What would you see on an OCT?
- 2nd stage- after background retinopathy (but NO new blood vessels formed yet)
- More severe and widespread changes affect the blood vessels (more vessels blocked)
- More significant bleeding into the eye – this is known as pre-proliferative retinopathy
OCT: - Soft exudates (Cotton wool spots- more places with ill- defined edges: hard exudate spots represent leakage, wheras soft exudates represent ischemia and are more serious)
- Haemorrhage
What is proliferative retinopathy?
- Last stage of retinopathy (new blood vessels form)
- Damaged blood vessels close off
- Causing the growth of new, abnormal blood vessels in the retina (esp around the optic disc)
- These new blood vessels are fragile and can leak
- Increases the risk of haemorrhage
- This is known as proliferative retinopathy and it can result in some loss of vision
What is Maculopathy? What would you see on an OCT?
- Maculopathy occurs when the leaked fluid builds up at the macula,
- leaking into the retina causing swelling
- Occasionally, the blood vessels in the macula become so constricted that the macula is starved of oxygen and nutrition causing your sight to get worse
OCT:
*Hard exudates/ oedema near the macula - Cotton wool spots (soft exudates)
How would you treat Background retinopathy?
General retinopathy treated with:
- Improve HbA1c
- stop smoking
- lipid lowering
- good blood pressure control <130/80 mmHg
BR specifically:
Continued annual surveillance
How would you treat pre-proliferative retinopathy?
General retinopathy treated with:
- Improve HbA1c
- stop smoking
- lipid lowering
- good blood pressure control <130/80 mmHg
PPR specifically:
(If left alone will progress to new vessel growth) so, early panretinal photocoagulation
What is panretinal photocoagulation?
Thermal burns in the peripheral retina leading to tissue coagulation, the overall consequence of which is improved retinal oxygenation
- prevents formation of new blood vessels BUT can cause peripheral vision damage
How would you treat Proliferative retinopathy?
General retinopathy treated with:
- Improve HbA1c
- stop smoking
- lipid lowering
- good blood pressure control <130/80 mmHg
PR specifically:
Panretinal photocoagulation
How would you treat diabetic maculopathy?
General retinopathy treated with:
- Improve HbA1c
- stop smoking
- lipid lowering
- good blood pressure control <130/80 mmHg
Maculopathy specifically:
- Oedema: Anti-VEGF injections directly into the eye (VEGF: vascular endothelial growth factor)
- Grid photocoagulation
What is diabetic nephropathy?
kidney damage caused by diabetes
Why is diabetic nephropathy important?
- Associated with progression to end-stage renal failure requiring haemodialysis
- Healthcare burden
- Associated with increased risk of cardiovascular events
How would you diagnose diabetic nephropathy?
- Progressive proteinuria (urine albumin:creatinine ratio - ACR): urine dipstick not accurate enough, annually screened/ tested
* Microalbuminuria >2.5 mg/mmol can be used as a v. early sign where most patients still have kidney function
* Proteinuria = ACR > 30mg/mmol
* Nephrotic Range > 3000mg/24hr - Increased blood pressure
- Deranged renal function (eGFR)
- Advanced: peripheral oedema (occurs in later stages
Describe the mechanism for diabetic nephropathy
- Hyperglycemia and hypertension leads to glomerular hypertension (pressure builds up in the glomerulus)
- Proteins are, therefore, forced/ leak out
- = proteinuria
- Causes damage to the glomerulus (decreased function)
- Leads to Glomerular and intersitial fibrosis and glomerular filtration rate decline
= RENAL FAILURE
What is the reltionship b/t nephropathy and the Renin- Angiotensin System?
System is more activated in patients with nephropathy
(treatment targets the RAS system)
How/ what parts of the RAS system are targeted in the treatment of nephropathy?
RAS system:
1. Liver releases Angiotensinogen
2. Kidney releases renin which converts the Angiotensinogen into Angiotensin I
3. ACE coverts Angiotensin I into Angiotensin II
4. Angiotensin II causes vasoconstriction and binds to Angiotensin receptors to promote the rlease of aldosterone (increasing salt/ water retention to increase bp/ hypertension)
Targets:
a. ACE inhibitors [ACEi] (antihypertensives which block ACE)
b. Angiotensin receptor blockers [ARBs] (antihypertensives which block the receptors)
DO NOT GIVE BOTH TOGETHER: EITHER OR
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 (give max dose tolerated by bp)
No benefit to having both ACEi/ARB simultaneously
Describe the relationship of microalbuminuria on the heart
Microalbuminuria is a risk factor for cardiovascular disease
How would you 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 (only used for T2DM, prevents glucose reabsorbtion in kidneys/ delays the progression of T2DM)
What is diabetic neuropathy?
“when diabetes causes damage to your nerves”
- 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 (ischemia will lead to damage)
What are the risk factors of diabetic neuropathy?
- Age (more likely to have prolonged alcohol intake0
- Duration of diabetes
- Poor glycaemic control
- Height (longer nerves in lower limbs of tall people)
- Smoking
- Presence of diabetic retinopathy
What areas of the body are commonly affected in neuropathy?
- Longest nerves supply feet – so more common in feet
- Commonly glove & stocking distribution (hands and lower limbs)– peripheral neuropathy
- Can be painful (worsens at night- can reduce sleep)
- Danger is that patients will not sense an injury to the foot (eg. stepping on a nail), so more likely to get diabetic foot ulcers
How do we track diabetic foot ulcerations?
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)
What can increase the risk of foot ulcerations
- reduced sensation to feet (peripheral neuropathy)
- poor vascular supply to feet (peripheral vascular disease)
How would you manage peripheral neuropathy (with no ulcerations)?
- Regular inspection of feet by affected individual
- Good footwear
- Avoid barefoot walking
- Podiatry and chiropody if needed (seeing a specialist)
How would you manage peripheral neuropathy (with ulcerations)?
- Multidisciplinary diabetes foot clinic
- Offloading
- Revascularisation if concomitant PVD
- Antibiotics if infected
- Orthotic footwear
- Amputation if all else fails
What is Monoeuropathy?
“damage that occurs to a single nerve”:
- Usually, sudden motor loss eg wrist drop, foot drop
- Cranial nerve palsy (palsy= lack of function) = double vision due to 3rd (oculomotor) nerve palsy (eye looks down and out)
What is autonomic neuropathy?
“Damage to sympathetic and parasympathetic nerves innervating GI tract, bladder, cardiovascular system”
1. GI tract
- Delayed gastric emptying: nausea and vomiting (can make prandial short-acting insulin challenging)
- Constipation / nocturnal diarrhoea (reduced peristalsis/ contractions) V. DIFFICULT TO TREAT
2. Cardiovascular
- Postural hypotension (low bp when standing up): can be disabling - collapsing on standing.
- Cardiac autonomic supply: sudden cardiac death
What are some examples of macrovascular complications?
Cerebrovascular disease
Ischaemic heart disease
Peripheral vascular disease (lower limb)
Why is it difficult to treat 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 some non modifiable risk factors of macrovascular disease?
Age
Sex
Birth weight
FH/Genes
What are some modifiable risk factors of macrovascular disease?
Dyslipidaemia (imbalance of lipids): statins to decrease cholesterol
Hypertension (ACEi/ ARBs)
Smoking
Diabetes mellitus
Central obesity “weight around the tummy” (produces hormones that antagonise insulin)
How would you manage 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
