Download Diabetic Complications Diabetic Neuropathy Multiple mechanisms

Diabetic Complications

Diabetic Neuropathy
 Multiple mechanisms with several manifestations:
 Peripheral sensory neuropathy
— Progression from loss of vibration sense → stocking distribution of
sensory loss, as if “walking on cotton wool” + loss of ankle jerk
 Mononeuropathies
— Affecting single nerve trunk e.g. CN III palsy
— Affecting >1 individual nerve trunk e.g. mononeuritis multiplex
 Amyotrophy
— Sudden onset, painful wasting & weakness of quads + loss of knee jerk
 Autonomic neuropathy
— Postural hypotension
— Loss of vagal tone (no sinus arrhythmia)
— Gastroparesis
— Diarrhoea
— Atonic bladder → UTI
— Impotence

Causes of peripheral neuropathy
 Alcohol
 B12 deficiency (+ SACDC)
 Chronic renal failure & Carcinoma
 Diabetes & Drugs e.g. nitrofurantoin, metronidazole, ethambutol, isoniazid
 Every vasculitis & CTD e.g. RA, scleroderma, PAN, Wegener’s

Large fibre neuropathy e.g. B12
 Affects large myelinated sensory nerves
 Negative Sx = unsteady gait with loss of JPS; ‘walking on cotton wool’ as loss
of discriminatory sensation
 Positive Sx = pins & needles, band-like feeling around calf

Small fibre neuropathy e.g. alcohol
 Affects small, unmyelinated C fibres
 Negative Sx = loss of pain & temperature sensation
 Positive Sx – painful dysasesthesiae e.g. burning causalgia, hyperalgesia
Peripheral neuropathy – prevented by good glycaemic control
 Polyneuropathy due to diffuse damage to nerves
 Affects longest nerves 1st i.e. those → feet (“length-dependent neuropathy”)
 Stocking pattern of sensory loss → loss of ALL modalities
 Loss of ankle jerk – loss of afferent arc of tendon reflex
 Mixed predominance of sensory loss:
— Some have predominantly painful neuropathy (mostly small ‘C’ fibres
affected; temp & pain)
— Others have little pain but profound loss of proprioception & unsteady
gait e.g. numbness, ‘walking on cotton wool’ (mostly large Aα & Aβ
fibres; proprioception & discriminatory touch)
 LOSS OF PROTECTIVE SENSATION = risk of injury, infection & gangrene
— Screening using monofilament: replicates 10g load when applied to skin
at 90o with just enough force to make it bend
— Applied at 3-5 sites on plantar aspect of foot & patient asked to report
when they can feel it (tip of big toe & 4th toe, 1st, 3rd & 5th MT heads)
 Combination of small vessel disease (nerve ischaemia) & metabolic factors
— Glycosylation of membrane proteins
— Oxidative stress
— Sorbitol (a slowly-metabolised sugar) accumulation
Diabetic Nephropathy
 Associated with long-standing poor glycaemic control
 ↑Risk of macrovascular disease with ↑ mortality as a result
 Can be detected early by screening for microalbuminuria (urinary Alb:Cr ratio >3)
 Intensive Rx in both type I & type II can ↓ risk
 Risk factor ↓ e.g. smoking, lipids, HTN
 ACEi – slow progression of renal impairment once microalbuminuria detected

Pathophysiology
 Hyperglycaemia → nephron loss
— 2o to BM thickening, mesangial proliferation & inflammation
 Nephron loss → RAAS activation
— Glomerular HTN → hyperfiltration of protein → ↑GFR &
microalbuminuria → tubular damage (glomerular sclerosis)
— Systemic HTN → macrovascular disease → ↑CVS mortality
 Progression → tubular damage → macroalbuminuria & ↓ GFR → impaired
renal function → ESRF


Microalbuminuria = >30mg/day
Macroalbuminuria = >0.5g/day
Normal capillaries
↓
BM thickening
(↑GFR & Microalbuminuria)
↓
Glomerulosclerosis – Kimmelstein-Wilson lesion
(Overt albumuria → Nephrotic syndrome)
↓
ESRF
(Uraemic symptoms)
Clinical features
 Asymptomatic initially → Later HTN, oedema & uraemia
Management
 Once microalbuminuria detected → ACEi regardless of BP (counteracts RAAS)
 Good glycaemic control
 Lipid-lowering agents
 Aspirin
 CRF = dialysis → transplant
Pre-proliferative DR:
 Venous beading/loops
 Intraretinal microvascular abnormalities (IRMA) –
dilated capillaries
 Cotton wool spots – infarct of nerve fibres
Proliferative DR:
 New vessel growth anywhere on retina –
tendency to bleed → vitreous haemorrhages
 Ischaemia → ↑ release of growth factors →
abnormal new vessels
 Rubeosis Iridis
 neovascularization of iris
 Neovascular glaucoma
 Haemorrhage → tractional retinal
detachment
Diabetic Retinopathy - 10yrs
 RF = nephropathy
 Background (maculopathy) → pre-proliferative →
proliferative → vitreous haemorrhage → retinal
detachment
Background DR: - no visual loss
 Microaneurysms
 Haemorrhages – dot, blots (deep retinal) & flame (superficial)
 Hard exudates – lipid leakage into deep retina
Diabetic Maculopathy:
 Background changes but at macula → visual loss
 Leakage of fluid distorts retinal architecture
 Exudative
 Ischaemic (Type I DM) – not treatable
Causes of Visual loss in DM
 Vitrous haemorrhage
 Retinal detachement involving macula
 Maculopathy
 Neovascular glaucoma
 ↑ Cataract prevalence
Treatment
 Good glycaemic & BP control
 Annual fundoscopy
 ↓ lipids = ↓ exudative maculopathy
 Photocoagulation: - ↓ prd of angiogenic factors
 Scattered laser pan photocoagulation – PDR
 Focal laser – exudative maculopathy
Other Eye Conditions Associated with DM
 Cataracts
 Check red reflex → ↓ in cataracts
 Chronic open angle glaucoma
 Optic disc cupping = glaucoma
 Corneal abrasions, retinal vein occlusion, CN III palsy