Long term complications of diabetes Flashcards
Which cells are able to reduce glucose transport in response to extracellular hyperglycaemia?
Retinal endothelial cells
Mesangial cells of glomerulus
Schwann cells and peripheral nerve cells
What is diabetic retinopathy?
A progressive ophthalmic microvascular complication of diabetes.
When does diabetic retinopathy present in T1 and T2 diabetics?
T1DM - after 3-5 years of diagnosis
T2DM - may already be present but 50-80% have it at 20 years post diagnosis.
What is the pathophysiology of retinopathy?
Glucose is metabolised to sorbitol within retinal cells by aldose reductase.
Increase in glucose = increase in sorbitol.
Accumulation of sorbitol in retinal cells causes oxidative stress and hypoxia. This alters PKC leading to increased Vascular Endothelial Growth Factor activity and dysregulation of permeability.
Neovascularisation –> Proliferative retinopathy (R)
Increased permeability –> Macula oedema (M)
What are the clinical features of diabetic retinopathy?
Floaters
Blurred vision
Reduced visual acuity
Loss of vision
What tests are used to determine diabetic retinopathy?
Visual acuity - Snellen chart
Fundoscopy
What are cotton wool spots?
Chronic ischaemia
How is diabetic retinopathy graded?
R = neovascularisation
R0, R1, R2, R3
M = Maculopathy
M1, M1, P
What Is R0?
No neovascularisation
What is R1?
Background neovascularisation e.g. Microaneurysm, retinal haemorrhages, hard exudates
What is R2?
Preproliferative neovascularisation
e.g. cotton wool spots, venous bleeding, loops, reduplication, intraretinal microvascular anomalies, multiple deep round or blot haemorrhages.
What is R3?
Proliferative neovascularisation
NVD - New vessel in disc
NVE - New vessel elsewhere
Preretinal or vitreous haemorrhage
Preretinal fibrosis +/- retinal detachment
What is M0?
No maculopathy
What is M1?
Maculopathy
Exudates within one disc diameter of centre of fovea, micro aneurysm, or haemorrhage within one disc diameter of centre of fovea associated with visual acuity <6/12.
What is P in the diabetic retinopathy grading scale?
Previous photocoagulation (laser therapy)
For those with R0 + R1, how often are they screened?
Annually.
For those with R3, how quickly should they be seen by an ophthalmologist?
Immediately.
For R2/MI, how quickly should they be seen by an ophthalmologist?
Within 4 weeks.
What treatment is given to those with diabetic retinopathy to prevent further deterioration/development?
Glycaemic control
BP control - Lisinopril
Fibrates (reduces risk of laser treatment in T2DM)
What specific treatments are given to those with diabetic retinopathy?
Photocoagulation
Intravitreal steroids - to reduce macular oedema + improve visual acuity
Vitrectomy - removal of opaque vitreous humour
Growth factor inhibitors - intravitreal bevacizumab. This reduces new vessel formation in retina.
What condition is this?
Rubeosis Iridis
End stage retinopathy - neovascularisation of the iris.
At what age do patients start diabetic eye screening?
From aged 12.
What is diabetic nephropathy?
Kidney damage caused by diabetes.
How is diabetic nephropathy defined?
Microalbuminuria - 30-300mg albumin in urine/day
Proteinuria >300mg/day - then there is a steady decline in eGFR
20-30% of diabetics will have developed diabetic nephropathy after how many years of their diabetic diagnosis?
10 years
In which ethnicities is the risk of diabetic nephropathy increased in?
African-Caribbean, Mexican and Pima Indians
What is the pathophysiology of nephropathy?
Increase in advanced glycation end products and growth factors leads to;
-Glomerular hyperfiltration
-Altered glomerular composition
-Renal hypertrophy
-Glomerular hypertension
These all lead to albuminuria and deposition of ECM –> Glomerulosclerosis and interstitial fibrosis.
Which histological changes are seen in diabetic nephropthy?
Expansion of mesangium
Glomerular BM thickening
Glomerular sclerosis
Fusion of foot processes
Loss of podocytes
What is the legacy affect?
Good control of blood sugars/HTN over a number of years reduces the risk of developing diabetic nephropathy.
How is diabetic nephropathy treated?
ACE or ARB for BP control
Glycaemia control
Lipid management
Protein restricted diet
What is diabetic neuropathy?
Where myelinated and unmyelinated nerve fibres are lost. More common in T1DM.
What are the metabolic risk factors for diabetic neuropathy?
Advanced glycosylation end-products (AGE’s)
Sorbitol –> Reduced Na-K-ATPase –> Slows conduction velocity
Oxidative stress
What are the vascular risk factors of diabetic neuropathy?
Morphological abnormalities and vasa nervorum
Thrombomodulin and tissue plasminogen activator levels reduced
Why are advanced glycosylated end products a risk factor for developing diabetic neuropathy?
Can lead to ROS + inflammation
Macrophages, chemokine and cytokines can signal further inflammation.
These lead to damage in Schwann cells.
Why does a poor production of growth stimulating factors such as nerve growth factor and neurotrophin 3 lead to diabetic neuropathy?
They are required for nerve growth and repair.
What is distal symmetrical polyneuropathy?
Glove and stocking distribution.
Loss of pinprick, temp, vibration and joint position with reduced ankle reflexes.
Which common deficiency can cause distal symmetrical polyneuropathy?
B12
What is polyradiculopathy?
Severe pain in 1+ nerve root distribution.
Usually resolves over 6-12 months.
What is mononeuropathy?
Affects a single cranial or peripheral nerve.
What is autonomic neuropathy?
Damage to nerves controlling involuntary functions.
What are the common presentations of autonomic neuropathy?
Cardiovascular - Resting tachycardia + postural hypotension
GI - Delayed gastric emptying
Genitourinary - Bladder dysfunction
Hypoglycaemic unawareness
Hyperhidrosis
What are the differential diagnoses for diabetic neuropathy?
Uraemia
B12 deficiency
Hypothyroidism
Amyloidosis
Toxins/Alcohol/Heavy nmetals
Inflammation
Infection - HIV, leprosy
Paraneoplastic syndromes
What analgesics are used to treated diabetic neuropathy?
Duloxetine
TCA’s
Gabapentin
What is peripheral vascular disease?
Arterial narrowing due to atheroma deposition.
A microvascular complication of diabetes.
What conditions is PVD associated with?
IHD
CVD
Hows do arteries get damaged in PVD?
Vasoconstriction - from HTN + vascular SMC growth
Inflammation - from chemokine and cytokine release
Thrombosis - increased viscosity
What are the clinical features of PVD?
Can be asymptomatic
Cramp on exertion
Reduced circulation
Leg discolouration
Ulcers
Hair loss to extremities
How test is used to identify PVD and what are the normal parameters?
ABPI (Ankle Brachial Pressure Index)
Normal 1.0 - 1.3
<0.9 - PVD
>1.3 - Calcification of vessels
What are the clinical features of diabetic foot ulcers?
Neuropathy
Ischaemia
Bony deformity
Callus
Swelling
Skin breakdown
Infection
Necrosis
What is osteomyelitis?
Inflammation of bone/bone marrow.
What factors increase the likelihood of osteomyelitis?
Visible bone
Bigger ulcer (>2cm x 2cm)
Bigger depth (>3mm)
Longer duration (>1-2 weeks)
ESR >70 per hour (Erythrocyte Sedimentation Rate)
How are diabetic foot ulcer treated?
Mechanical offloading
Debridement
Abx
Amputation
What is Charcot arthropathy?
Sudden onset unilateral warmth, redness and oedema over foot/ankle, usually with a hx of minor trauma.
Slowly progressive over months/years, results in collapse of the arch and bony deformities.
How is Charcot arthropathy treated?
Avoid weight bearing
PO/IV Bisphosphonates
What condition is this?
Acanthosis nigricans
What condition is this?
Diabetic dermopathy
What condition is this?
Necrobiosis lipoidica diabeticorum
Is there a risk of IHD with a low HbA1C?
Yes - due to hypoglycaemia.
also increases the risk of CVD.
