(endo) microvascular and macrovascular complications of diabetes mellitus Flashcards
define microvascular (complications of diabetes)
long-term complications that affect small blood vessels
e.g. neuropathy, nephropathy, retinopathy
define macrovascular (complications of diabetes)
long-term complications that affect large blood vessels
e.g. cerebrovascular disease, ischaemic heart disease, peripheral vascular disease
what increases the risk of developing microvascular complications of diabetes?
1) extent of hyperglycaemia i.e. HbA1c levels
2) rising systolic BP and risk of MI
what are the target HbA1c levels to reduce the risk of microvascular complications?
53 mmol/mol
how do increasing HbA1c levels affect microvascular complications of diabetes?
= increase risk of microvascular complication in the following order
1) retinopathy
2) nephropathy
3) neuropathy
4) microalbuminuria
prevention of microvascular complications in diabetes requires reduction in which two parameters mainly?
1) HbA1c
2) blood pressure
besides HbA1c and BP, which factors increase the risk of developing microvascular complications?
1) (longer) duration of diabetes
2) smoking
3) genetic factors
4) hyperlipidaemia
5) hyperglycaemic memory
explain the link between duration of diabetes and risk of developing microvascular complications
the longer a patient has had diabetes + associated hyperglycaemia, the more likely they are to develop microvascular complications
explain the link between hyperlipidaemia and risk of developing microvascular complications
the greater the levels of hyperlipidaemia, the greater the risk of developing microvascular complications of diabetes
explain the link between smoking and risk of developing microvascular complications
smoking causes endothelial dysfunction
= increased risk of microvascular complications
explain the link between genetic factors and risk of developing microvascular complications
some individuals may be genetically prone to developing microvascular complications despite having reasonable glycaemic control
what is hyperglycaemic memory?
the idea that individuals with a period of past poor glycaemic control may have caused irreversible damage in such a way that increases the risk of complications
(despite the chance that the patients may NOW have good glycaemic control)
explain the link between hyperglycaemic memory and risk of developing microvascular complications
inadequate glucose control in the past can result in a higher risk of complications, even if HbA1c is improved now
how does hyperglycaemic memory come about?
periods of hyperglycaemia (poorly controlled)
= can cause epigenetic modifications
= increase the risk of complications
(does not matter if HbA1c is improved/better controlled now)
briefly explain the mechanism of damage in terms of microvascular complications
hyperglycaemia + hyperlipidaemia
= oxidative stress
= increased formation of mitochondrial superoxide free radicals in the endothelium
= activation of inflammatory signalling cascade
= inflammation + endothelial damage
= leaky capillaries, ischaemia (+ retinopathy, nephropathy, neuropathy)
why are the effects of persistent hyperglycaemia long-lasting?
poorly-controlled persistent hyperglycaemia causes long-lasting epigenetic modifications
= persistent expression of pro-inflammatory genes
= even if HbA1c is better controlled now, there is always an increased risk of complications
what is diabetic retinopathy?
a microvascular complication of diabetes that causes damage to the vessels supplying the retina
what is diabetic retinopathy the main cause of?
- visual loss in people w diabetes
- blindness in people of working age
why is annual retinal screening essential in people with diabetes?
patients are usually asymptomatic in the early stages of diabetic retinopathy
= SO, screening is essential to identify + treat it early while treatment is still possible and before visual loss/blindness
what are the possible stages of diabetic retinopathy?
- background retinopathy
- pre-proliferative retinopathy
- proliferative retinopathy
- maculopathy
what are the characteristic features of background retinopathy?
- hard exudates (cheese colour, as a result of lipid leakage)
- microaneurysms
- blot haemorrhages
why do hard exudates form in background retinopathy?
inflammation of the vessels supplying the retina
= leads to leaky capillaries
= lipid leakage
what are the characteristic features of pre-proliferative retinopathy?
- soft exudates (i.e. cotton wool spots)
= form due to retinal ischaemia
what occurs in pre-proliferative retinopathy that leads to the formation of soft exudates?
retinal ischaemia
due to endothelial dysfunction as a result of inflammation of the retinal capillaries
what are the characteristic features of proliferative retinopathy?
- formation of new blood vessels (visible)
why does angiogenesis occur in proliferative retinopathy?
inflammation of the retinal capillaries = endothelial dysfunction = retinal ischaemia = hypoxia = compensatory angiogenesis
what is the implication of angiogenesis in proliferative retinopathy?
the new vessels that form in the retina as part of the compensatory angiogenesis are very weak + friable
= prone to rupture
= increased risk of haemorrhages
what are the characteristic features of maculopathy?
- hard exudates (cheese colour, lipid leakage, oedema)
- blot haemorrhages, microaneurysms
= same disease as background retinopathy BUT happens to be near the macula
= threatens vision
why is maculopathy particularly dangerous?
= same disease as background retinopathy w hard exudates, oedema and haemorrhages BUT happens to be near the macula
= site of CENTRAL VISION
= so, maculopathy threatens vision
how is background retinopathy treated?
1) improve HbA1c + lipid levels, stop smoking
2) good blood pressure control of < 130/80 mmHg
3) CONTINUED ANNUAL SURVEILLANCE
how is pre-proliferative retinopathy treated?
1) improve HbA1c + lipid levels, stop smoking
2) good blood pressure control of < 130/80 mmHg
3) EARLY PANRETINAL PHOTOCOAGULATION
why is panretinal photocoagulation commonly done for patients with pre-proliferative retinopathy?
to prevent progression onto proliferative retinopathy
i.e. formation of new, friable blood vessels
how is proliferative retinopathy treated?
1) improve HbA1c + lipid levels, stop smoking
2) good blood pressure control of < 130/80 mmHg
3) PANRETINAL PHOTOCOAGULATION
how is diabetic maculopathy treated?
1) improve HbA1c + lipid levels, stop smoking
2) good blood pressure control of < 130/80 mmHg
3) anti-VEGF injections for oedema
4) GRID PHOTOCOAGULATION
why are anti-VEGF used to treat diabetic maculopathy?
in diabetic maculopathy, fluid build-up + swelling in the retina (oedema)
= so anti-VEGF reduce the thickening of the macula and improve vision
what is panretinal photocoagulation?
the preferred form of treatment for proliferative retinopathy
= wherein a laser is used to burn through the layers of the retina to prevent the formation of new blood vessels
= reducing the risk of haemorrhages
why is diabetic nephropathy important?
- associated with progression to end-stage renal failure requiring haemodialysis
- associated with an increased risk of cardiovascular events
= healthcare burden
which parameter is measured to assess renal function in patients w diabetes?
ACR (urine albumin-creatinine ratio)
what is the earliest hallmark of diabetic kidney disease?
microalbuminuria
i.e. >2.5mg/mmol loss of protein
what are the features of more advanced diabetic kidney disease?
- increased blood pressure (i.e. hypertension)
- deranged renal function (eGFR)
very advanced:
- peripheral oedema (due to fluid imbalance)
list the progressive stages of protein loss in diabetic nephropathy
1) microalbuminuria (>2.5 mg/mmol)
2) proteinuria (>30 mg/mmol)
3) nephrotic syndrome (>3000mg/24hr) = extremely rare
what are the parameters for microalbuminuria in diabetic nephropathy?
ACR of >2.5mg/mmol
what are the parameters for proteinuria in diabetic nephropathy?
ACR of >30mg/mmol
what are the parameters for nephrotic syndrome in diabetic nephropathy?
proteinuria greater than 3000mg/24 hours
= extremely rare but very large amounts of protein are lost in the urine
explain the mechanism of diabetic nephropathy briefly
hypertension + hyperglycaemia = glomerular hypertension = endothelial damage = proteinuria = glomerular/interstitial fibrosis = GFR declines = renal failure
briefly summarise the RAAS system
- angiotensinogen (produced in the liver) is converted into angiotensin I by renin (released from the renal JGA)
- angiotensin I is converted into angiotensin II by ACE (produced in the liver)
- angiotensin II then acts on the zona glomerulosa of the adrenal cortex to stimulate aldosterone production
what are ACE inhibitors?
anti-hypertensives that inhibit the lung enzyme, ACE and prevent conversion of angiotensin I into angiotensin II
= reducing aldosterone production
= reducing hypertension
briefly summarise how ARBs work
ARB = angiotensin receptor blocker
how are people at risk of diabetic nephropathy most commonly managed?
- block RAAS with
1) ACE inhibitor (-pril)
2) ARB (-sartan)
= reduces blood pressure + progression of diabetic nephropathy
what measure must be taken to manage patients with diabetes that have microalbuminuria/proteinuria?
must be either on an ACEi/ARB even if normotensive
= as a precautionary measure
(no benefit to simultaneous intake)
in patients w diabetes, what is microalbuminuria a risk factor for?
development of cardiovascular disease
people w microalbuminuria = increased risk of stroke, MI etc
list the ways in which diabetic nephropathy is managed
- aim for tighter glycaemic control
- reduce BP to < 130/80
- start ACEi/ARB if microalbuminuria (even if normotensive)
- stop smoking
(- start SGLT-2 inhibitor if T2DM?)
what is diabetic neuropathy and how does it occur?
the blood vessels supplying the nerves are termed the vasa vasorum
when the vasa vasorum are damaged as a result of diabetes, nerve functioning can consequently be impaired
= neuropathy
what can diabetic neuropathy lead to?
lower limb amputation
diabetes mellitus is the most common cause of neuropathy which can lead to LLA
what are the wider implications of diabetic neuropathy?
impaired nerve function
= lack of pain sensation + lack of wound sensation
what are the risk factors of diabetic neuropathy?
- age
- smoking
- height
- duration of diabetes
- poor glycaemic control
- presence of diabetic retinopathy
how is the duration of diabetes a risk factor for diabetic neuropathy?
the longer the patient has had diabetes, the greater the time they have been exposed to hyperglycaemia
= greater potential for more damage
how is height a risk factor for diabetic neuropathy?
in the limbs of tall people, there are longer nerves
= more prone to damage
= greater/wider implications if they are damaged
how is diabetic retinopathy a risk factor for diabetic neuropathy?
the presence of microvascular disease somewhere in the body increases the risk of the same elsewhere in the body
what regions of the body are most commonly affected by diabetic neuropathy?
1) glove + stocking distribution = most commonly, peripheral neuropathy
2) longest nerves affected (i.e. the ones that supply the feet)
explain why diabetic neuropathy is commonly painful
damage to the blood vessels supplying nerves
= impaired nerve function
= lack of pain/wound sensation
= more prone to not realising when they are injured
= greater scope for infection
(+ reduced healing ability due to poor/impaired blood supply to the region)
why are patients w diabetes at risk of foot ulceration?
1) reduced sensation to feet (due to peripheral neuropathy)
2) reduced healing due to poor vascular supply (peripheral vascular disease)
how is the risk of diabetic foot reduced?
all people w diabetes = annual foot check
what does the annual foot check for people w diabetes consist of?
- look for foot deformity/ulceration
- assess sensation (monofilament, ankle jerks)
- assess foot pulses (dorsalis pedis, posterior tibial)
why do people w diabetes have poor healing rates for wounds?
poor vascular supply due to damage to the blood vessels
= reduced ability to heal wounds
how is peripheral neuropathy managed?
- regular inspection of feet by affected individuals
- good footwear
- avoid barefoot walking
how is peripheral neuropathy with ulceration managed?
- MDT foot clinic
- revascularisation (if PVD)
- orthotic footwear
- antibiotics
- amputation, if all else fails
why are flip flops & socks risky for people who may develop diabetic foot disease?
1) flip flops = open-toed so increased risk fo damage + debris
2) socks = increased risk of blister formation
define mononeuropathy
when damage occurs to a single nerve
= that can cause individual pain, numbness or sudden loss of movement (e.g. wrist/foot frop)
give an example of a mononeuropathy
oculomotor nerve palsy (i.e. 3rd nerve palsy)
= cranial nerve palsy that can cause diplopia
what is autonomic neuropathy?
damage to sympathetic and parasympathetic nerves innervating GI tract, bladder, cardiovascular system
what are the implications of autonomic neuropathy on the GI tract?
- delayed gastric emptying
- vomiting + nausea (can make post-prandial short-acting insulin a problem)
- constipation/nocturnal diarrhoea
what are the implications of autonomic neuropathy on the cardiovascular system?
- postural hypertension (can be disabling i.e. collapsing on standing)
- cardiac autonomic supply impaired = sudden cardiac death
list the possible macrovascular complications of diabetes
- ischaemic heart disease
- peripheral vascular disease
- cerebrovascular disease
how is macrovascular disease prevented and why?
need to target and aggressively manage MULTIPLE risk factors
why is it inefficient to target only hyperglycaemia when managing macrovascular complications?
targeting only hyperglycaemia = minor effect of increased cardiovascular
= so to target the CVR as effectively as possible, = need to address multiple risk factors
how does the presence of T1DM affect CVR?
the presence of T1DM increases cardiovascular risk + mortality
what are the non-modifiable risk factors for macrovascular complications in diabetes?
- age
- sex
- birth weight
- family history/genetics
what are the modifiable risk factors for macrovascular complications in diabetes?
- diabetes mellitus
- hypertension
- dyslipidaemia
- smoking
- central obesity
list five ways in which cardiovascular risk is managed in diabetes mellitus
1) reduce/control blood pressure
2) control lipid profile
3) weight loss
4) stop smoking
5) annual urine microalbuminuria screen
what is the desired blood pressure in patients w diabetes?
normally <140/80 mmHg
but if MICROVASCULAR complications in patient then <130/80 mmHg
what is the desired lipid profile in patients w diabetes?
total cholesterol < 4
LDL < 2
how is weight managed in patients w diabetes?
- lifestyle interventions
- pharmacogloical interventions
why is an annual urine microalbuminuria screen recommended for patient w diabetes?
microalbuminuria is a risk factor for cardiovascular disease
what is the biggest risk associated with neuropathy?
risk of foot ulceration with peripheral neuropathy
what is the biggest risk associated with nephropathy?
associated w cardiovascular risk
microalbuminuria
