Diabetic ComplicationsDiabetic 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
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
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
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
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
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
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