Microvascular complications

Question 1

What are the main sites of microvascular complications of diabetes mellitus?

Answer 1

Retinal arteries.
Glomerular arterioles (kidney).
Vaso nervorum (blood vessels that supply nerves).

Question 2

What factors affect the risk of developing microvascular complications of diabetes mellitus?

Answer 2

Severity of hyperglycaemia.
Hypertension.
Genetics.
Hyperglycaemic memory.
Tissue damage through originally reversible and later irreversible alterations in proteins.

Question 3

What is the mechanism of glucose damage in diabetes mellitus leading to microvascular complications?

Answer 3

Hyperglycaemia and hyperlipidaemia lead to AGE-RAGE, oxidative stress and hypoxia, which lead to inflammatory signalling cascades.
Inflammatory signalling cascades lead to local activation of pro-inflammatory cytokines, then inflammation.
Inflammation leads to nephropathy, retinopathy and neuropathy.

Question 4

What are pathways can worsen glucose damage in diabetes mellitus?

Answer 4

Polyol pathway.
AGEs.
Protein kinase C.
Hexosamine.

Question 5

What is the main cause of visual loss in people with diabetes?

Answer 5

Diabetic retinopathy.

Question 6

What is the main cause of blindness in people of working age?

Answer 6

Diabetic retinopathy.

Question 7

What are the clinical features of background diabetic retinopathy?

Answer 7

Leakage of protein through vessels.
Hard exudates (cheese colour, lipid).
Microaneurysms (‘dots’).
Blot haemorrhages.

Question 8

What are the clinical features of pre-proliferative diabetic retinopathy?

Answer 8

Cotton wool spots, a.k.a. soft exudates, represent retinal ischaemia.
Pre-retinal haemorrhage.

Question 9

What are the clinical features of proliferative retinopathy?

Answer 9

Visible new vessels form, on disc or elsewhere in retina.

Can bleed to cause visual loss, or directly affect vision.

Question 10

What are the clinical features of maculopathy?

Answer 10

Hard exudates near the macula.
Same disease as background retinopathy, but happens to be near macula.
This can threaten direct vision.

Question 11

What is the management strategy for background diabetic retinopathy?

Answer 11

Improve control of blood glucose.

Warn patient that warning signs are present.

Question 12

What is the management strategy for pre-proliferative (cotton wool spot) diabetic retinopathy?

Answer 12

Suggests general ischaemia.
If left alone, new vessels will grow.
Needs pan-retinal photocoagulation.

Question 13

What is the management strategy for proliferative (visible new vessels) diabetic retinopathy?

Answer 13

Pan-retinal photocoagulation.

Question 14

What is the management strategy for maculopathy?

Answer 14

Only have problem around macula.

Need only a grid of photocoagulation (not pan-retinal).

Question 15

What are the features of diabetic nephropathy?

Answer 15

Hypertension.
Progressively increasing proteinuria.
Progressively deteriorating kidney function.
Classic histological features.
Albuminuria.

Question 16

What are the histological features of diabetic nephropathy?

Answer 16

Glomerular: mesangial expansion, basement membrane thickening, glomerulosclerosis.
Vascular.
Tubulointerstitial.

Question 17

Discuss the epidemiology of diabetic nephropathy.

Answer 17

T1DM: 20-40% after 30-40 years.
T2DM: probably equivalent, but depends on age at development of disease, racial factors, age at presentation and loss due to cardiovascular morbidity.

Question 18

What are the clinical features of diabetic nephropathy?

Answer 18

Progressive proteinuria.
Increased BP.
Deranged renal function.

Question 19

What are the different ranges for proteinuria?

Answer 19

Normal range = <30mg/24hrs.
Microalbuminuric range = 30-300mg/24hrs.
Asymptomatic range = 300-3000mg/24hrs.
Nephrotic range = >3000mg/24hrs.

Question 20

What are the strategies for intervention in diabetic nephropathy?

Answer 20

Diabetic control: decreasing HbA1c reduces risk of microvascular complications.
Blood pressure control.
Stopping smoking.
Inhibition of the activity of RAS system: beneficial effect of ACE inhibitors on diabetic nephropathy.

Question 21

What are the effects of angiotensin II?

Answer 21

Vasoactive effects.
Mediation of glomerular hyperfiltration.
Increased tubular uptake of proteins.
Induction of profibrotic cytokines.
Stimulation of glomerular and tubular growth.
Podocyte effects.
Induction of proinflammatory cytokines.
Generation of ROS and NF-kB.
Stimulates fibroblast proliferation.
Up regulation of adhesion molecules on endothelial cells.
Up regulation of lipoprotein receptors.

Question 22

What is the most common cause of lower limb amputation?

Answer 22

Diabetes mellitus, because it is the most common cause of neuropathy.

Question 23

What are the different features of diabetic neuropathy?

Answer 23

Peripheral polyneuropathy.
Mononeuropathy.
Mononeuritis multiplex.
Radiculopathy.
Autonomic neuropathy.
Diabetic amyotrophy.

Question 24

What is neuropathy?

Answer 24

Small vessels supplying nerves are called vasa nervorum.

Neuropathy results when these vessels get blocked.

Question 25

Describe the initiation/progress of neuropathy as a disease.

Answer 25

Initiating event: inflammation (oxidative/nitrative stress) or genetics.
Neuronal injury: glycation (AGEs).
Functional changes: epigenetic (PARPs, etc.)
Progressive pathological changes.
Takes months to years.

Question 26

What is peripheral neuropathy, and why is it a problem?

Answer 26

Longest nerves supply feet.
Loss of sensation.
More common in tall people.
Danger is that patients will not sense an injury to the foot (e.g. stepping on a nail)- may need amputation if becomes infected.
Loss of ankle jerks.
Loss of vibration sense (using tuning fork).
Multiple fractures on foot x-ray (Charcot’s joint).

Question 27

What patients is peripheral neuropathy more likely to occur in?

Answer 27

Tall patients.

Patients with poor glucose control.

Question 28

How do you test for peripheral neuropathy in a clinical setting?

Answer 28

Monofilament examination.

Question 29

What is mononeuropathy?

Answer 29

Usually sudden motor loss.
Wrist drop, foot drop.
Cranial nerve palsy, e.g. double vision due to 3rd nerve palsy.

Question 30

What is pupil sparing third nerve palsy?

Answer 30

Eye is usually ‘down and out’.
6th nerve pulls eye out, 4th nerve pulls it down.
Pupil does respond to light.
Third nerve not functioning.
Related to diabetes or vascular disease.
Parasympathetic fibres on outside, thus they do not easily lose blood supply in diabetes.

Question 31

What are the signs of a space occupying lesion (aneurysm or tumour) that causes a third nerve palsy?

Answer 31

Will press on parasympathetic fibres first, causing fixed dilated pupil.

Question 32

What is mononeuritis multiplex?

Answer 32

A random combination of peripheral nerve lesions.

Question 33

What is radiculopathy?

Answer 33

Pain over spinal nerves, usually affecting a dermatome on the abdomen or chest wall.

Question 34

What is autonomic neuropathy?

Answer 34

Loss of sympathetic and parasympathetic nerves to GI tract, bladder, cardiovascular system.
GI tract: difficulty swallowing, delayed gastric emptying, constipation/nocturnal diarrhoea, bladder dysfunction, vomiting, gastroparesis.
Postural hypotension- can be disabling, collapsing on standing.
Cardiac autonomic supply- case reports of sudden cardiac death.

Question 35

How is autonomic neuropathy diagnosed?

Answer 35

Clinical examination and history.
Measure changes in heart rate in response to Valsalva manoeuvre.
Normally there is a change in heart rate.
Look at ECG and compare R-R intervals.