Microvascular Complications Flashcards
What are the main sites of microvascular complications in DM?
- Retinal arteries
- Glomerular arterioles (kidney)
- Vasa nervorum (tiny blood vessels that supply nerves)
What is the relationship between the severity of hyperglycaemia and microvascular disease?
- microvascular complications tend to develop according to the severity of hyperglycaemia
- the higher the sugar the higher the likelihood that your patient will develop them
What is a normal HbA1c?
- below 6%
- anything above 6.5% is diabetes
- both micro and macrovascular disease increase with higher HbA1c
What is the relationship between hypertension and microvascular disease?
- as BP increases, so does the risk of microvascular disease
What factors influence microvascular disease?
- severity of hyperglycaemia
- hypertension
- genetics
- hyperglycaemic memory (someone who has recently been diagnosed with DM and control well right
What is meant by hyperglycaemic control?
- Patitents have better outcomes if their blood glucose is well controlled from the start
- e.g. someone who was diagnosed 5 years ago and had good control from the start vs. someone who had poorly controlled diabetes for a number of years.
- problem: T2DM is more common but also less symptomatic in the beginning -> sometimes some of the damage has been done at the time of diagnosis
- screening is important especially in obese patients with FH od diabetes
- The risk of microvascular disease dramatically decreases if the sugar is controlled well.
What are the mechanisms of glucose damage?
- hyperglycaemia and hyperlipidaemia cause
a) AGE RAGE
b) oxidative stress
c) hypoxia - this in turn causes inflammatory signalling cascade
- this causes local activation of pro-inflammatory cytokines
- this causes inflammation
- inflammation causes nephropathy, retinopathy and neuropathy
(the basic mechanism is increasing the amount of cytokines)
What is diabetic nephropathy?
- Diabetic retinopathy is the main cause of visual loss in people with diabetes and the main cause of blindness in people of working age
- very common in patients with diabetes
- diabetes causes retinal ischeamia which in turn causes vessel damage in the eye.
What is the macula important for?
color vision
Background diabetic retinopathy
- Hard exudates (cheese colour, lipid)
- Microaneurysms (“dots”)
- Blot haemorrhages
Protein goes out of vessles
Bulging out
Bleeding from vessles
Pre-proliferative diabetic retinopathy
- Cotton wool spots also called soft exudates
- Represent retinal ischaemia
- vessels leaking out protein
if you don’t treat background retinopathy
Proliferative diabetic retinopathy
- Visible new vessels
- On disk or elsewhere in retina
- the vessles are not oriented, they are going around.
What is the main cause of blindness in people of work g age?
diabetic retinopathy
When are cotton wool spots seen?
- In pre-proliferative diabetic retinopathy
- they are caused by:
Maculopathy
- Hard exudates near the macula
- Same disease as background, but happens to be near macula
- This can threaten direct vision
How do you manage (background) diabetic retinopathy?
- improve control of blood glucose
- warn patient that warning signs are present
- retinal scan 1x/year
- eye changes don’t happen immediately, they are slow changes
How do you manage (pre-proliferative) diabetic retinopathy?
- Pre-proliferative (cotton wool spot)
- Suggests general ischaemia
- If left alone, new vessels WILL grow
- Needs: Pan retinal photocoagulation (Small laser beams fired at the back of the retina to prevent new vessles from forming)
How do you manage proliferative diabetic retinopathy?
- Proliferative (visible new vessels)
- Also needs: Pan retinal photocoagulation (Small laser beams fired at the back of the retina to prevent new vessles from forming)
- the vessles will bleed if they are not treated
How do you manage maculopathy?
- Only have problem around macula
- Needs only a GRID of photocoagulation
(NOT pan retinal photocoagulation)
What is a GRID of photocoagulation? When is it used?
- used in maculopathy
- ???????????
Which statement is correct regarding diabetic retinopathy?
a) Progression is unrelated to glycaemic control
b) Cotton wool spots are a feature of background retinopathy
c) Hard exudates are always treated with pan retinal photocoagulation
d) Maculopathy can threaten direct vision
e) Proliferative changes are best left untreated
d) is true
Why is diabetic nephropathy important?
- Associated morbidity and mortality (having kidney disease increases the risk of dying very much)
- Health care burden (financially)
- Treatment options present (good BP, good glucose, smoking cessation)
What is an effect of DM and CKD?
- presence of DM and CKD increases the risk of cardiovascular events
- the highest prevelance of kidney disease is in the diabetes cohort
In which cohort is the highest prevalence of kidney disease?
In the diabetes cohort
Histological features of kidney disease?
- glomerular
- vascular
- tubulointerstitial
Histological features of kidney disease - glomerular changes?
- Mesangial expansion
- Basement membrane thickening
- Glomerulosclerosis
Clinical features of diabetic nephropathy?
- Progressive proteinuria
- Increased BP
- Deranged renal function
What is the epidemiology of nephropathy in diabetics?
- Type 1 DM : 20-40% after 30-40 years
- Type 2 DM : Probably equivalent - BUT in T2DM they tend to be quite young at diagnosis and love with it for a long time. T2DM is diagnosed much later in life (around 40-50) so they ???????????rewatch that part of the lecture
Epidemiology of nephropathy in T2DM
- Age at development of disease
- Racial Factors
- Age at presentation
- Loss due to cardiovascular morbidity (they may die of a heart attack before they have problems with their eyes or kidneys)
Proteinuria ranges
- Normal Range <30mg/24hrs
- Microalbuminuric Range 30 - 300mg/24hrs
- Assymptomatic Range 300 - 3000mg/24hrs
- Nephrotic Range >3000mg/24hr
Sometimes very small protein cannot be detected on the dipstick which is why you measure microalbumin which if elevated is an early sign of kidney disease.
What are strategies for intervention in diabetic nephropathy?
- diabetes control - decrease blood glucose
- 37% decrease in risk of microvascular complications per 1% decrement in HbA1c
- BP control
- inhibition of the activity of the RAAS
- smoking cessation (something that kills patients with Kideny problems is cardiovascular disease)
It is very good to prevent the progression of kidney disease
What is a normal GFR? What GFR would require dialysis?
- normal is around 90
- around 30 would require dialysis
- ACE inhibitors are quite good for kidney function
Angiotensin 2
- Vasoactive effects
- Mediation of glomerular hyperfiltration
- Increased tubular uptake of proteins
- Induction of pro fibrotic cytokines
- Stimulation of glomerular and tubular growth
- Podocyte effects
- Induction of pro inflammatory cytokines
- Generation of ROS & NF-kB
- Stimulates fibroblast proliferation
- Up regulation of adhesion molecules on endothelial cells
- Up regulation of lipoprotein receptors
Negative effects of Angiotensin 2
- Vasoactive effects -> detritus effects on the kidneys
- Mediation of glomerular hyperfiltration
- Increased tubular uptake of proteins
- Induction of pro fibrotic cytokines
- Stimulation of glomerular and tubular growth
- Podocyte effects
- Induction of pro inflammatory cytokines
- Generation of ROS & NF-kB
- Stimulates fibroblast proliferation
- Up regulation of adhesion molecules on endothelial cells
- Up regulation of lipoprotein receptors
Which of these are features of diabetic nephropathy?
a) Affects all patients with diabetes over time
b) Associated with decreased blood pressure
c) Progressively increasing proteinuria
d) Unrelated to glycaemic control
e) Associated with a low risk of cardiovascular events
a) not the ones with good sugar and BP control that don’t smoke
b) associated with high BP
c) true
d) dalse
e) false
Which of these are features of diabetic nephropathy?
a) Affects all patients with diabetes over time
b) Associated with decreased blood pressure
c) Progressively increasing proteinuria
d) Unrelated to glycaemic control
e) Associated with a low risk of cardiovascular events
a) not the ones with good sugar and BP control that don’t smoke
b) associated with high BP
c) true
d) false
e) false
Diabetic neuropathy
- Diabetes is the most common cause of neuropathy and therefore lower limb amputation
- Small vessels supplying nerves are called vasa nervorum
- Neuropathy results when these get blocked
Neuropathy: disease initiation/progress
????????
Neuropathy: disease initiation/progress
INFLAMMATION
genetics, epigenetics, glycation
