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