Micro and macro vascular complications of diabetes

Question 1

What are the three sites of diabetes related microvascular complications?

Answer 1

Retinal arteries (retinopathy), renal glomerular arterioles (nephropathy), vasa nervosum (neuropathy)

Question 2

Describe the relationship between HbA1c and microvascular complications

Answer 2

Extent of hyperglycaemia (as determined by HbA1c levels) is strongly associated with increased risk of developing micro vascular complications

Question 3

What HbA1c level should those with diabetes aim for to prevent development of microvascular comlications?

Answer 3

<53 mmol/mol

Question 4

Aswell as HbA1c (glycemic levels) what is the other main factor that contributes to risk of microvascular complications?

Answer 4

Hypertension. Both HbA1c and BP control required

Question 5

Other than HbA1c and BP, what are the other factors related to microvascular complications?

Answer 5

Duration of diabetes, smoking, genetic factors, hyperlipidaemia, hyperglycaemic memory (previously high HbA1c levels)

Question 6

Outline the general mechanism of damage to the microvasculature?

Answer 6

Oxidative stress (high lipid/ glucose) leads to increased formation of mitochondrial superoxide free radicals in the endothelium. This leads to generation of AGEs (advanced glycation end products) which results in activation of inflammatory pathways f damaging the endothelium

Question 7

What is diabetic retinopathy?

Answer 7

Damage to the blood vessels in the retina

Question 8

Why is annual retina screening offered to all diabetes patients?

Answer 8

The early stages of diabetic retinopathy are asymptomatic. Screening needed to detect retinopathy at a stage where it can still be treated before causing visual disturbances

Question 9

What stage of diabetic retinopathy is the only stage that can be treat?

Answer 9

Background retinopathy (first stage)

Question 10

Outline the mechanism of diabetic retinopathy

Answer 10

• activation of many pathways in the presence of hyperglycaemia
• leads to dysfunction in the endothelium
• leads to retinal ischaemia
• this produces factors which increase permeability -> macular oedema, neovascularisation

Question 11

What are the 4 stages of diabetic retinopathy?

Answer 11

1- background retinopathy.
2 - pre-proliferative retinopathy
3- proliferative retinopathy
4- maculopathy

Question 12

What are the characteristic of background retinopathy (as seen on a retinal screen)?

Answer 12

Hard exudates – cheese colour, lipid (leaked fluid and associated proteins) appear near end of vessels. Microaneurysms (dots) and blot haemorrhages (paint splatters)

Question 13

What are the characteristics of pre-proliferative retinopathy (as seen on a retinal screen)?

Answer 13

Cotton wool spots aka soft exudates (fuzzier), these are representative of retinal ischaemia

Question 14

What are the characteristics of proliferative retinopathy (as seen on a retinal screen)?

Answer 14

Visible new vessels (neovascularisation) on retinal disc or elsewhere in the retina

Question 15

What are the characteristics of maculopathy (as seen on a retinal screen)?

Answer 15

Hard exudates/oedema near the macula, same disease as background retinopathy but near macula therefore can threaten direct vision

Question 16

How is diabetic retinopathy treated?

Answer 16

Improve HbA1c
Improve BP control
Continued annual surveillance and feedback to person living w/diabetes
Pan-retinal photocoagulation

Question 17

What is pan-retinal coagulation?

Answer 17

Burn vessels off to stop neovascularisation

Question 18

When would grid laser therapy be offered to someone with diabetic retinopathy?

Answer 18

When there’s neovascularisation around the macula

Question 19

What treatment is given for maculopathy?

Answer 19

anti-VEGF (vascular endothelial growth factor) injections directly into the eye to treat oedema. Grid photocoagulation

Question 20

Diabetic nephropathy is characterised by what four things?

Answer 20

Hypertension
Progressively increasing proteinuria
Progressively deteriorating kidney function
Classic histological features

Question 21

Why is diabetic nephropathy clinically important?

Answer 21

Associated with progression to end-stage renal failure, associated with increased risk of cardiovascular events

Question 22

Outline the basic mechanism of diabetic nephropathy

Answer 22

Hyperglycaemia and hypertension as a result of diabetes leads to glomerular hypertension resulting in proteinurea and a decline in glomerular filtration rate

Question 23

What are the consequences of diabetes with kidney disease?

Answer 23

Increases risk of macro vascular complications -> congestive heart disease, acute MI, cerebral vascular accident, peripheral vascular disease

Question 24

What are the histological features of diabetic nephropathy?

Answer 24

Glomerular changes such as mesangial expansion, basement membrane thickening, glomerulosclerosis

Question 25

What things modify risk of someone with diabetes developing nephropathy?

Answer 25

Age at development of disease, age at presentation, ethnic differences (African-Caribbean)

Question 26

What positive tests are indicative of diabetic nephropathy?

Answer 26

Progressive proteinuria, increased BP, deranged renal function (eGFR) and peripheral oedema in advanced stage

Question 27

What is the first line of treatment for diabetic nephropathy?

Answer 27

Aim for tighter glycaemic control, reduce BP - usually through ACEi or ARB, stop smoking, start an SGLT2 inhibitor if T2DM

Question 28

Why is blocking RAS useful for diabetic nephropathy?

Answer 28

Reduces: Mediation of glomerular hyperfiltration, increased tubular uptake of proteins, induction of pro-fibrotic cytokines, stimulation of glomerular and tubular growth, fibroblast proliferation, upregulation of adhesion molecules on endothelial cells

Question 29

What is the most common cause of neuropathy and therefore amputation?

Answer 29

Diabetes

Question 30

What causes neuropathy?

Answer 30

Blockage of the vasa nervorum

Question 31

What are the risk factors associated with development of diabetic neuropathy?

Answer 31

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

Question 32

How is diabetic foot disease managed?

Answer 32

Regular inspection of feet, good footwear, avoid barefoot walking

Question 33

What are the clinical features associated with diabetic neuropathy?

Answer 33

Loss of sensation, loss of propioception in toes/legs

Question 34

What is mononeuropathy?

Answer 34

Neuropathy of a single nerve - usually sudden motor loss e.g. wrist drop. Cranial nerve palsy: e.g double vision due to third nerve palsy (eye looks down and out)

Question 35

What is autonomic neuropathy?

Answer 35

Loss of sympathetic and parasympathetic nerves to GI tract, bladder and cardiovascular system.

Question 36

What are the modifiable risk factors of macro vascular diabetes complications?

Answer 36

Dyslipidaemia, hypertension, smoking, diabetes, central obesity

Question 37

What are the non-modifiable risk factors associated with macrovascular diabetes complications?

Answer 37

Age, sex, birth weight, Genes

Question 38

What are the three types of macro vascular complications of diabetes?

Answer 38

Cerebrovascular disease, ischaemic heart disease, peripheral vascular disease

Question 39

How does treatment targeted at macro vascular complications of diabetes differ from treatment for micro vascular?

Answer 39

In macrovascular, treatment targeted to hyperglycaemia alone has minor effects, requires management of multiple risk factors

Question 40

What are the multiple risk factors that need to be managed alongside hyperglycaemia to treat macro-vascular complications of diabetes?

Answer 40

Smoking status, blood pressure, lipid profile, weight, annual urine microalbuminuria screen

Question 41

Why is Acanthosis nigiricans associated with Type 2 diabetes?

Answer 41

Associated with insulin resistance, excess insulin causes skin cells to reproduce at a rapid rate

Question 42

What questions allows us to distinguish between erectile dysfunction due to testosterone deficiency or due to diabetes?

Answer 42

Loss of early morning erections/libido. Loss of erections due to diabetes

Question 43

To decrease lipid profile and reduce risk of macro vascular complications what should be prescribed?

Answer 43

A statin

Question 44

To decrease risk of micro or macro-vascular complications in a diabetes patient with microalbuminurea what should be prescribed?

Answer 44

An ACE inhibitor