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
What cane done to detect diabetic nephropathy in its early stages?
Screen for microalbuminaemia every year from diagnosis
What medication is used in the presence of microalbuminaemia to prevent progression onto macroalbuminaemia?
ACE in inhibitors and angiotensin II receptor blockers
Other than direct medication, what can be done to prevent progression to macroalbuminmemia?
Aggressive CV risk reduction using statins, reducing blood pressure (<125/75), stop smoking
Improve glycaemic control (<7%)
Refer to renal clinic once they develop CKD (i.e. GFR <30)
What was the finding from UKPDS with relation to microalbuminaemia?
Strict glycaemic control prevents microalbuminaemia (intensive regime)
How does diabetic neuropathy arise?
Capillary damage in diabetic patients includes the vasa nervorum
Reduced blood supply to the neural tissue results in impairment in nerve signalling that affect both sensory and motor function
In what 3 ways does glucose lead to the inability for nerves to transmit signals?
Metabolic damage - sorbitol accumulation
Vascular changes - endothelial damage
Structural changes
Put the following clinical signs in chronological order:
- loss of reflexes
- vibratory sensation loss
- nerve conduction abnormalities
- decrease in pressure sensation
- Nerve conduction abnormalities
- Decrease in vibratory sensation
- Decrease in pressure sensation
- Loss of reflexes
What are the NICE 2012 guidelines for the treatment of diabetic neuropathy?
Duloxetine (or amytriptyline)
Amitriptyline (or pregabalin)
Refer to pain clinic
- try tramadol
- try topical lidocaine
Diabetic foot is a combination of neuropathy and peripheral vascular disease. What are 3 features of diabetic foot?
Infection
Ulcers
Ischaemia
In what ways can diabetic neuropathy be tested? (in the foot)
Pin-prick test
Tuning fork on ankle
Tendon jerk reflexes
In the classification relating to risk of diabetic neuropathy, what is the presentation of the following classifications and how often would review occur as a result?
a) Low risk
b) Medium risk
c) High risk
a) Normal sensation and pulses - annual review
b) Neuropathy OR absent pulses - review by podiatrist every 3-6 months
c) Deformities OR ulceration - review by podiatrist every 1-3 months
How many amputations per week in the UK take place as a result of diabetic foot?
100
What is the 5 year mortality rate for those with diabetic foot (amputation(?))?
80% (only 50% of people survive 2 years)
What is charcot foot?
Weakening of the bone of the foot - occurs in people with significant neuropathy
How does numb feet in diabetic neuropathy contribute to charcot foot?
Can lead to repetitive micro trauma (as patient cannot feel pain)
Can get stress fractures (cannot feel pressure)
How does the dysregulated blood flow resulting from diabetic neuropathy contribute to charcot foot?
Increases bone turnover (as ischaemic bone would have to be replaced)
Fragile bone
What sign is present in charcot foot?
Inverted arch of the foot
Describe the effects of autonomic neuropathy with relation to:
a) Cardiovascular system
b) Genito-urinary system
c) Gastrointestinal system
a) Postural hypotension
b) Erectile dysfunction
c) Gustatory sweating (after eating food)
Gastroparesis
What is diabetic amyotrophy?
Painful proximal neuropathy
Usually in the thigh/buttock
What is mono neuritis multiplex?
Painful, asymmetrical motor and sensory neuropathy - affects 2 or more nerves
List the biochemical tests in the annual review.
HbA1c
Cholesterol, HDL TG
Creatinine
Microalbuminaemia
List the general checks that take place in the annual review
Lifestyle - smoking, exercise, diet
Drug therapy
Mental well-being
List the health checks relating to microvascular disease in the annual review
BP Visual acuity Retinal screening Pedal pulses Foot sensation BMI
List the two genito-urinary aspects of the annual review
Erectile dysfunction
Contraception
Why is glycaemic control in pregnancy important?
HbA1c at time of conception is key to reducing risk of congenital abnormalities
Glycaemic control during pregnancy can help prevent macrosomia (large birth weight and size)
Around what % of T1DM patients have an insulin pump?
5%
What are the issues surrounding the use of an insulin pump?
No background insulin
Risk of DKA
TRaining/self-management required
