micro and macro vascular complications

Question 1

what are the micro and macro vascular complications of diabetes?

Answer 1

micro:
retinopathy
neuropathy
nephropathy

macro:
cerebrovascular disease
ischaemic heart disease
peripheral vascular disease

Question 2

what is the relationship between HbA1c and risk of microvascular complications?

Answer 2

the extent of hyperglycaemia (judged by HbA1c) is strongly associated with increased risk of developing microvascular complications

target HbA1c to reduce risk of micro complications is
53 mmol/mol

you should aim to be below this but that can be quite hard

Question 3

how is hypertension related to risk of microvascular complications?

Answer 3

clear relationship
as systolic BP rises, risk of MI and microvascular complications increases in people with T1DM and T2DM

<130/80 mmHg

Question 4

what two main factors should be controlled to reduce risk of microvascular complications?

Answer 4

HbA1c <53 mmol/mol

blood pressure

Question 5

what are other factors that relate to development of microvascular complications?

Answer 5

duration of diabetes (gets bad above 40 years)
smoking - endothelial destruction
genetic factors (develop complications despite reasonable glycaemic control)
hyperlipidaemia
hyperglycaemic memory - inadequate glycaemic control early in in disease can result in higher risk of microvascular complications later, even with improved HbA1c

Question 6

what are the mechanisms of damage in microvascular complications?

Answer 6

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, and ischaemia

Question 7

what is diabetic retinopathy?

Answer 7

main cause of:
visual loss in people with diabetes
blindness in people of working age

the early stages of retinopathy are asymptomatic
:. screening is needed

aim of screening: detect retinopathy early when it can be treated before it causes visual disturbance/loss

:. there is annual retinal screening for all diabetes patients in the UK

Question 8

what does a normal retina look like?

Answer 8

look up pictures

optic disc appears as a light circle towards one edge
blood vessels emerging from near optic disc and extending round the eye
macula (aka fovea, responsible for central, high resolution, colour vision) appears as a darker circle in the middle

Question 9

what are the 4 stages of retinopathy?

Answer 9

background retinopathy
pro-proliferative retinopathy
proliferative retinopathy
maculopathy

each is progressively worse

Question 10

what is background retinopathy?

Answer 10

hard exudates (cheese colour, lipid)
micro aneurisms (appear as white dots)
blot haemorrhages

some white dots
some red dots or splodges

Question 11

what is pre-proliferative retinopathy?

Answer 11

cotton wool spots (aka soft exudates)
these represent retinal ischemia

still has red splodges, haemorrhages from background retinopathy
larger ares of white dots/splodges, these are the cotton wool spots

Question 12

what is proliferative retinopathy?

Answer 12

visible new vessels
can be on disc or elsewhere in retina

the new blood vessels appear due to all the previous damage, but they are very friable

Question 13

what is maculopathy?

Answer 13

same disease as background retinopathy but it happens to be near the macula

hard exudates / oedema near the macula
can be cotton wool spots too

this can threaten vision

Question 14

what is the treatment associated with each stage of retinopathy?

Answer 14

throughout: HbA1c <53 mmol/mol, BP <130/80 mmHG

background retinopathy: continued annual screening

pro proliferative retinopathy: if left alone will proceed to next stage
so early panretinal photocoagulation

proliferative retinopathy: panretinal photocoagulation

diabetic maculopathy:
oedema - anti VEGF injections directly into the eye
grid photocoagulation

(VEGF: vascular endothelial growth factor. so anti VEGF stops one of the inflammatory cause and prevents formation of new vessels)

Question 15

what is pan-retinal photocoagulation?

Answer 15

photo coagulation: burn through areas where there is new vessel formation, stops vision from getting worse
looks like little round burns
it stops new vessels from forming and any further haemorrhage
affects peripheral vision

Question 16

why is diabetic nephropathy important?

Answer 16

associated with progression to end stage renal failure requiring haemodialysis (although not a certainty)

healthcare burden

associated with an increased risk of cardiovascular events

Question 17

how is diabetic nephropathy diagnosed?

Answer 17

progressive proteinuria (urine albumin:creatinine ratio - ACR)

increased blood pressure

deranged renal function (eGFR)

advanced: peripheral oedema

FIRST SIGN is microalbuminuria: >2.5 mg/mmol
and then raised creatinine and declining eGFR come later

proteinuria = ACR >30 mg/mmol

nephrotic range= >3000 mg/24hr
but this is uncommon

Question 18

what is the mechanism of diabetic nephropathy?

Answer 18

diabetes leads to hypertension and hyperglycaemia

–> glomerular hypertension

–> proteinuria

–> glomerular and interstitial fibrosis

–> glomerular filtration rate decline

–> renal failure

Question 19

what is the renin angiotensin system (RAS) and how is it blocked?

Answer 19

angiotensin produced by liver
renin, produced by kidneys, turns it to angiotensin I
ACE turns angiotensin I to angiotensin II

effects of Angiotensin II:
vasoconstriciton
aldosterone production from zona glomerulosa of adrenal cortex
effectively raises blood pressure

this system is in overdrive in diabetic nephropathy

angiotensin II acts via angiotensin receptors
ACE inhibitors (ACEi) are antihypertensives which block ACE
angiotensin receptor blockers (ARBs) are antihypertensives

Question 20

how is diabetic nephropathy related to RAS?

Answer 20

blocking the RAS with and ACEi (-pril) or ARB (-sartan) reduces blood pressure and progression of diabetic nephropathy

all diabetes patients with microalbuminuria/proteinuria should be on an ACEi/ARB even if they arent hypertensive

(there is no benefit of having an ACEi and ARB simultaneously)

Question 21

how is microalbuminuria related to CVD?

Answer 21

microalbuminuria leads to increased risk of:
ischemic stroke
myocardial infarction
all cause mortality

Question 22

how is diabetic nephropathy managed?

Answer 22

aim for tighter glycaemic control

ACEi or ARB as soon as microalbuinuria is detected iven if patient is normotensive

reduce BP (<130/80 mmHg) usually through ACEi/ARB

stop smoking

start on an SGLT-2 inhibitor if T2DM?

Question 23

what is diabetic neuropathy?

Answer 23

diabetes mellitus is the most common cause of neuropathy and therefore lower limb amputation

small vessels supplying the nerves are called vasa nervorum
neuropathy results when vasa nervorum get blocked

amputation may because people cant feel their feet when they are wounded

longest nerves supply the feet, so more common here
commonly glove and stocking distribution - peripheral neuropathy
can be painful

Question 24

what are the risk factors of diabetic neuropathy?

Answer 24

age
duration of diabetes
poor glycaemic control
height (longer nerves in the lower limbs of tall people)
smoking
presence of diabetic retinopathy

Question 25

what is diabetic foot check?

Answer 25

all people with diabetes should get an annual foot check
looks for:
foot deformity, ulceration
assess sensation (monofilament, ankle jerks)
assesses foot pulses (dorsalis pedis and posterior tibial)

there is an increased risk of ulceration inpatients with:
reduced sensation to feet (peripheral neuropathy)
poor vascular supply to feet (peripheral vascular disease) (need blood to heal)

Question 26

how is diabetic foot disease managed?

Answer 26

peripheral neuropathy:
1. regular inspection of feet by patient
2. good footwear
3. avoid barefoot walking
podiatry and chiropody if needed

peripheral neuropathy with ulceration:

1. multidisciplinary diabetes foot clinic
2. offloading
3. revascularisation if concomitant PVD
4. antibiotics if infected
5. orthotic footwear
6. amputation if all else fails

Question 27

what is mononeuropathy?

Answer 27

another neuropathy that is sometimes seen in diabetes

usually sudden motor loss.
eg wrist drop or foot drop

cranial nerve palsy:
double vision due to 3rd nerve palsy

Question 28

what is autonomic neuropathy?

Answer 28

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 hypertension - can be disabling, collapsing on standing
cardiac autonomic supply - sudden cardiac death

Question 29

what are the macrovascular complications?

Answer 29

ischaemic heart disease
cerebrovascualr disease
peripheral vascular disease

treatment targeted ti hyperglycaemia alone has a minor effect on these

it requires aggressive management of multiple risk factors

risk increased with age
true for both T1DM and T2DM

Question 30

what are the risk factors for macrovascular complications?

Answer 30

non modifiable:
age
sex (women have a protective effect before menopause)
birth weight
FH/genes

modifiable:
dyslipidaemia
hypertension
smoking
diabetes mellitus
central obesity

Question 31

how is cardiovascular risk managed in diabetes?

Answer 31

support quitting smoking

blood pressure:
<140/80 mmHg, <130/80 if microvascular complications

lipid profile - total chol <4, LDL<2

weight - discuss lifestyle intervention +/- pharmacological treatments

annual urine microalbuminuria screen - risk factor for CVD