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1

Cellular mechanism of microvascular complications

High blood glucose= too much glucose into cells
- Some cell types are unable to control glucose entry when there is excess efflux

Leads to cell damage
- Peripheral nerve cells, Schwann cells
- Retinal cells [endothelial]
- Mesangial cells of glomerulus

Complications take many years to develop

2

Microvascular complications for T1 DM

Rarely occur if DM has occurred in less than 5-10 years
- Due to steep decline of insulin

3

Retinopathy
- Pathology

Neovascularisation
- Death of BV causes new, small ones to be created
- Small new vessels are more fragile and susceptible to rupture.

- Loss of pericytes

- Thickening of basement membrane

- Closure of capillary causes ischaemia
Release VEGF,
Leaky capillaries: proteins released [causes 'white spots' in retina]

4

Retinopathy epidemiology

Diabetic cause is the 2nd most common cause of blindness.

5

Treatment of diabetic retinopathy

Controlling blood sugar and BP.

Laser treatment
- Pan retinal [burn the peripheral retina]
- Focal

Anti VEGF ab
- injected into retina

6

Peripheral neuropathy

Glove and stocking syndrome
- Loss of sensation in the feet that rises to hands.

Neuropathic foot ulcers that can present as callous

Charcot foot
- Deformed foot from inflammation, broken bones

7

Mononeuropathy

Loss of function of a single nerve

Includes carpel tunnel [entrapment neuropathy]

8

Autonomic neuropathy

Dysfunction of the ANS nerves
- CVD problems [postural hypotension]
- Gastroparesis
- Erectile dysfunction
- Diarhhoea
- Gustatory sweating

9

Nephropathy in diabetes
- Epidemiology

Most common cause of end stage kidney disease in western world
- 21% of death in T1, 11% in T2.

Tends to present with other microvascular complications
- Retinopathy

10

Nephropathy pathology

Thickening of BM

Loss of podocytes

Scaring- glomerular sclerosis

Mesangial expansion

Increases CVD risk

11

Diabetic nephropathy treatment

Reducing BP
- ACEi and ARBs

Glucose control important but overt proteinuria

12

Macrovascular disease treatment

Controlling risks
- BP
- Lipids
- Smoking

Glucose control not as important compared to microvascular

13

UKPDS

Diabetes study
- Assessed the outcome of controlling glucose in diabetic patients

Risk reduction took 15 years for significant reduction in risk.

Whereas controlling BP saw greater reduced risk of microvascular event.
- Significance seen at 5 years

14

DCCT

Diabetes control and complications trail

Glycosated haemoglobin does not show linear correlation with increased risk of microvascular events
- Therefore reducing glycated haemoglobin at one level does not have the same effect as at another level.

15

Clinical stages of retinopathy

Non-proliferative

Proliferative
- Diabetic retinopathy mechanism

Macular oedema
- Sight or non sight threatening