327-332. Microvascular complications of diabetes Flashcards
What factor is important in the prevention of microvascular disease?
Glycaemic control
What factors are important in the prevention of macrovascular disease?
Cholesterol
Blood pressure
Smoking
Glycaemic control isn’t as important
What are the two main aspects of the pathogenesis of microvascular disease?
Capillary damage
Metabolic damage
How are capillaries damaged in microvascular disease?
Increased blood flow leads to increased capillary pressure
Thickened and damaged vessel walls
Enodthelial damage
- leakage of albumin and other proteins
What are the two landmark trials which demonstrated the importance of glycaemic control in reducing the incidence of microvascular complications?
DCCT - published NEJM 1993
- conventional (2 injections/day) vs intensive regime (4 injections/day)
UKPDS - published Lacnet 1998
- conventional vs intensive regime
What was the finding in DCCT and UKPDS studies regarding the glycosylated haemoglobin levels in conventional and intensive regimes?
Why is this important?
The conventional regime had much higher percentages of glycosylated haemoglobin in comparison to the intensive regime
Important as the higher the percentage of HbA1c, the greater the risk of microvascular complications
What is the role of aldose reductase?
Metabolism of glucose to sorbitol
What parts of the body do not rely on insulin for the uptake of glucose?
Nerves, retina, kidney
What happens if glucose levels rise with relation to microvascular disease?
Excessive glucose enters the polyol pathway
- Sorbitol accumulates
- Less NADPH available for cell metabolism
- Build up of ROS and oxidative stress
- Cell damage
What did the DCCT trial show between the conventional and intensive therapy with relation to diabetic retinopathy?
As time goes on, the percentage of those with diabetic retinopathy increases, but those on intensive therapy showed a much smaller percentage of people presenting with diabetic retinopathy
In the early stages of diabetic retinopathy (non-proliferative), what is the visible presentation of the following:
a) Hyperglycaemia
b) Breached vessel wall
c) Protein and fluid left behind
Micro-infarcts
a) Damage to small vessel wall, micro aneurysms
b) dot haemorrhages
c) hard exudates
d) cotton-wool spots
What are three aspects of the later stages of diabetic retinopathy?
Venous damage
Ischaemia -> activation of VEGF and other growth factors
Fluid not cleared from macular area - macular oedema
What are two ways in which veins can be damaged in the later stages of diabetic retinopathy?
Venous budding
Blockage of blood supply
What are the 3 ways in which the activation of VEGF and other growth factors in response to ischaemia lead to late stage diabetic retinopathy?
Neovascularisation
Proliferative retinopathy
Vitreous haemorrhage
What are 3 ways to prevent diabetic retinopathy?
Good glycaemic control
Stop smoking
Good blood pressure control
How can diabetic retinopathy be treated?
Address risk factors
Opthalmic review
- VEGF inhibitors (bevacizumab)
- laser
- vitrectomy
At what age should diabetic patients start being screened for diabetic retinopathy and how often after that should they attend screening?
Age 12; annually
What are the four stages of diabetic nephropathy?
- Renal enlargement and hyperfiltration
- Microalbuminaemia
- Macroalbuminaemia
- End stage renal failure