🧪Endocrinology🧪 - Micro/Macrovascular Complications of Diabetes

Question 1

What are the 2 types of vascular complications you can get from DM?

Answer 1

Microvascular
Macrovascular

Question 2

What are the microvascular complications of DM?

Answer 2

Retinopathy
Nephropathy
Neuropathy

Question 3

What are the macrovascular complications of DM?

Answer 3

Cerebrovascular disease
Ischaemic heart disease
Peripheral vascular disease

Question 4

What is the association between extent of hyperglycaemia and microvascular complications?

Answer 4

Extent/severity of hyperglycaemia (measured by HbA1c) is strongly associated with increased risk of microvascular complications

Question 5

What is the target HbA1c to reduce the risk of microvascular complications?

Answer 5

53 mmol/mol (<7%)

Question 6

What is the relationship between hypertension and complication risk?

Answer 6

Rise of systolic BP leads to increase in risk of microvascular complications and myocardial infarction

Question 7

What are the other factors related to the development of microvascular complications?

Answer 7

Duration of diabetes
Smoking - endothelial dysfunction
Genetic factors
Hyperlipidaemia
Hyperglycaemic memory

Question 8

What is meant by hyperglycaemic memory in the context of microvascular complications?

Answer 8

Inadequate glucose control early on can result in higher risk of complications LATER, even if HbA1c improved - some damage is already done

Question 9

What is the overall mechanism of vascular damage in DM?

Answer 9

Activation of inflammatory pathways
Damaged endothelium results in:
-‘Leaky’ capillaries
-Ischaemia
(diagram is for context - not memorisation)

Question 10

What is diabetic retinopathy a problem?

Answer 10

Leading cause of:
-Visual loss in people with diabetes
-Blindness in people of working age

Question 11

Why does diabetic retinopathy need to be screened for?

Answer 11

Early stages are asymptomatic
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

Question 12

What are the 4 types of diabetic retinopathy that will be experienced, from least to most severe?

Answer 12

Background retinopathy
Pre-proliferative retinopathy
Proliferative retinopathy
Diabetic maculopathy

Question 13

What causes diabetic retinopathy?

Answer 13

High blood sugar damages retinal vessels, causing leakage and ischemia.
Neovascularization occurs as the retina tries to compensate, but these new vessels are fragile and may rupture
Leakage and ischaemia, compounded with new fragile vessels, disrupt retinal function

Question 14

What is background retinopathy?

Answer 14

Leaks of fluids/lipids disrupts retinal function
No new vessel formation (can progress)
Hard exudates, microaneurysms, blot haemorrhages

Question 15

What is pre-proliferative retinopathy?

Answer 15

Intermediate stage of diabetic retinopathy
Multiple retinal haemorrhages, venous abnormalities (such as beading and looping), and areas of ischemia
These changes signal worsening retinal damage and increased risk of progression to proliferative retinopathy, where abnormal blood vessel growth (neovascularization) can occur, leading to severe vision loss if untreated

Question 16

What is proliferative retinopathy?

Answer 16

Ischaemic damage to retina due to lack of endothelial integrity has lead to neovascularisation
Major retinal disruption
Progression of background retinopathy -> pre-proliferative -> proliferative retinopathy

Question 17

What is maculopathy?

Answer 17

Same as retinopathy, but happens to be near the macula
Much more serious threat to macular vision

Question 18

What is the treatment plan for all retinopathies?

Answer 18

Improve HbA1c, stop smoking, lipid lowering
Achieve good BP control (<130/80mmHg)

Question 19

What is the treatment plan for background retinopathy?

Answer 19

Continued annual surveillance

Question 20

What is the treatment plan for pre-proliferative retinopathy?

Answer 20

If left alone will progress to new vessel growth
So, early panretinal photocoagulation

Question 21

What is the treatment plan for proliferative retinopathy?

Answer 21

Panretinal photocoagulation

Question 22

What is the treatment plan for diabetic maculopathy?

Answer 22

Oedema: Anti-VEGF injections directly into the eye (VEGF: vascular endothelial growth factor)
Grid photocoagulation

Question 23

What is photocoagulation?

Answer 23

Burning of blood vessels using a high power laser
Prevent proliferation of blood vessels

Question 24

What is an adverse effect of photocoagulation?

Answer 24

Loss of vision in the target retina

Question 25

Why is diabetic nephropathy clinically important?

Answer 25

Associated with progression to end stage renal failure - haemodialysis needed Healthcare burden Associated with increased risk of cardiovascular events

Question 26

What is microalbuminuria and what is it's significance?

Answer 26

Small amount of albumin in urine Early sign of kidney damage in nephropathy

Question 27

What is the ACR?

Answer 27

Albumin to creatinine ratio

Question 28

Why is the ACR useful?

Answer 28

It gives a ratio, so accounts for changes in urine concentration and GFR More albumin could mean further kidney damage or just a higher rate of filtration, so ACR accounts for this More reliable assessment of kidney damage

Question 29

What is the threshold for proteinuria in terms of ACR?

Answer 29

ACR>30mg/mmol

Question 30

What is the significance of proteinuria exceeding 3000mg/24hr?

Answer 30

Significant level of proteinuria from severe damage to glomeruli Nephrotic syndrome

Question 31

What is the next step for a patient with a UACR indicative of proteinuria?

Answer 31

**Repeat the test** False positives are quite common Causes include, fever, urine infection etc...

Question 32

Outline the mechanism of diabetic nephropathy

Answer 32

Question 33

What system is a key target for drugs aiming to help treat diabetic nephropathy?

Answer 33

Renin-angiotensin system (RAS)

Question 34

What are the 2 types of drugs that can block the RAS?

Answer 34

ACE inhibitors (ACEi) - inhibits production of angiotensin 2 Angiotensin receptor blockers (ARBs) - prevents binding of angiotensin 2 to its receptors

Question 35

What is the suffix for ACE inhibitors?

Answer 35

-pril

Question 36

What is the suffix for ARBs?

Answer 36

-sartan

Question 37

Why is there no benefit to using ACEi/ARBs in combination?

Answer 37

ACEi prevents production of A2, therefore ARBs not needed and not affected

Question 38

What should a diabetes patient with microalbuminuria/proteinuria be given if they are normotensive?

Answer 38

Still give ACEi/ARBs

Question 39

Why is the correlation between microalbuminuria and cardiovascular disease?

Answer 39

Strong correlation Strong ties to microalbuminuria being a risk factor

Question 40

What is the management plan for a patient with diabetic nephropathy?

Answer 40

Aim for optimal glycaemic control (HbA1c <53 mmol/mol) 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 (reduces risk of progression of chronic kidney disease)

Question 41

How does diabetic neuropathy arise?

Answer 41

Small vessels supplying nerves are called vasa nervorum Neuropathy results when vasa nervorum get blocked

Question 42

What are the risk factors for diabetic neuropathy?

Answer 42

Age Duration of diabetes Poor glycaemic control Height (longer nerves in lower limbs of tall people) Smoking Presence of diabetic retinopathy

Question 43

How does diabetic neuropathy present?

Answer 43

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 (e.g. stepping on a nail)

Question 44

What is a major concern with diabetic neuropathy that requires screening?

Answer 44

Diabetic foot ulceration (also foot injury in general)

Question 45

How is diabetic foot ulceration avoided and describe the check

Answer 45

All people with diabetes: annual foot check Look for foot deformity, ulceration Assess sensation (monofilament, ankle jerks) Assess foot pulses to assess circulation (dorsalis pedis and posterior tibial)

Question 46

How does diabetic neuropathy lead to foot ulcerations?

Answer 46

Reduced sensation to feet (peripheral neuropathy) Poor vascular supply to feet (peripheral vascular disease)

Question 47

What is the management of diabetic foot disease if affected by peripheral neuropathy?

Answer 47

Regular inspection of feet by affected individual Good footwear Avoid barefoot walking Podiatry and chiropody if needed

Question 48

What is the management of diabetic foot disease if affected by peripheral neuropathy with ulceration?

Answer 48

Multidisciplinary diabetes foot clinic Offloading Revascularisation if concomitant PVD Antibiotics if infected Orthotic footwear Amputation if all else fails

Question 49

What other neuropathies can occur due to diabetic neuropathy?

Answer 49

Mononeuropathy Usually, sudden motor loss eg wrist drop, foot drop Cranial nerve palsy double vision due to 3rd (oculomotor) nerve palsy Autonomic neuropathy

Question 50

What are the implications of autonomic neuropathy?

Answer 50

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

Question 51

How are macrovascular diseases managed/prevented?

Answer 51

Aggressive management of multiple risk factors

Question 52

What are the modifiable risk factors for macrovascular complications (therefore can be targeted with the goal of prevention)?

Answer 52

Dyslipidaemia Hypertension Smoking Diabetes Mellitus Central obesity

Question 53

What are the non-modifiable risk factors for macrovascular disease?

Answer 53

Age Sex Birthweight FH/Genes

Question 54

What are the steps for managing cardiovascular risk in diabetes mellitus?

Answer 54

Smoking status – support to quit Blood pressure - <130/80 mmHg if microvascular complication or increased metabolic risk (NB often needs multiple agents) Lipid profile – total cholesterol <4, LDL <2 Weight – discuss lifestyle intervention +/- pharmacological treatments Annual urine microalbuminuria screen – risk factor for cardiovascular disease