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Complications of Diabetes Mellitus
Dr Rodney ItakiLecturer
Anatomical Pathology Discipline
University of Papua New GuineaSchool of Medicine & Health SciencesDivision of Pathology
Clinical approach to Complications of DM
Acute Complications Ketoacidosis (Type I DM) Hyperglycemic hyperosmolar non-ketotic
syndrome (Type II DM) HypoglycaemiaChronic Complications Macrovascular - hypertension Microvascular – neuropapthies,
nephropathies & retinopahty
Pathological Approach to Complications of DM
• Microangiopathy – small vessel disease• Retinopathy• Nephropathy• Neuropathy
• Underlying cause is hyperglycemia
Pathogenesis
• Nonenzymatic Glycosylation• Formation of irreversible
glycosylation products with protein (e.g collagen) in blood vessels and interstitial tissues.
• Rather than dissociating, undergo series of slow series of chemical rearrangement that is irreversible forming Advanced Glycosylation End Products (AGE).
• AGE resistant to enzymatic proteolysis
Disturbance in Polyol Pathway
• Occurs in nerves, lens, kidneys & blood vessels. Do not need insulin for glucose intake.
• Osmotic cell injury
• Impairs ion pumps - Schwann cells (peripheral & autonomic neurophathy), pericytes in retinal capillaries. (retinal microaneurysm)
Ref: Robins Pathological Basis of Diseases, 6th Ed.
Morphology of Diabetes Complications• Pancreas: Most changes & more distinctive in
Type I than Type II DM.– Reduction in number and size of islets– Leukocyte infiltration of islets (T lymphocytes
mostly).– Eosinophil infiltrates
• Amyloid replacement of islets in Type II. Islets obliterated in advanced Type II DM.
• Vascular system: atherosclerosis of all vessels. Hyaline thickening of the wall of arterioles causing narrowing of lumen.
• Diabetic microangiopathy: Diffuse thickening of BM of capillaries (skin, skeletal muscle, retina, renal glomeruli, renal medulla, renal tubules, Bowman’s capsule, peripheral nerves, and placenta). Hyaline material forming concentric layers – type IV collagen. Despite thickened BM, capillaries more leaky than normal to plasma proteins.
Morphology of Diabetes Complications
• Diabetic nephropathy: glomerular lesions, renal vascular lesions (arteriosclerosis) & pyelonephritis, including necrotizing papillitis.– Glomerular lesions – capillary BM
thickening, diffuse glomerularsclerosis, nodular glomerularsclerosis.
– Renal vascular lesions – part of systemic involvement of blood vessels. Both afferent and efferent arterioles.
– Pyelonephritis – due to acute or chronic inflammation. Begins in the interstitial tissue and spread to affect tubules.
– Papillary necrosis more common in diabetics.
Morphological Complications of Diabetes
• Diabetic Ocular complications: take the form of retinopathy, cataract formation and glaucoma.
• Retinopathy – backgound (nonproliferative) & proliferative rentinopathy
• Background retinopathy– BM thickening,– pericyte degeneration. Loss results in microaneurysms– capillary microaneurysms (hemorrhages)– Microvascular obstructions and non-perfusion of
capillaries in posterior fundus that lack pericytes and endothelium. Cause hypoxia(cotton-wool spots).
– Arteriolar hyalinization causing BM thickening.– Gradual increase in retinal vein caliber as response to
ischaemia. Form venous loops and beading in veins.
Morpholigical Complications of Diabetes
• Proliferative retinopathy – characterised by neovascularisation and fibroplasia. – Neovascularisation occurs in response to
hypoxia of retina.– ischemic retinal cells produce VEGF (vascular
endothelial growth factor) inducing angiogenesis from larger veins and arterial vessels.
– new vessels incompletely formed & poorly supported and move with eye movements resulting in haemorrhages.
– Fibroplasia results later & contribute to retinal detachment
• Diabetic Neuropathy: central and peripheral nervous system. Pattern is of peripheral, symmetric neuropathy of lower limbs affecting both motor and sensory function.
Morphological complications of diabetes
• Peripheral neuropathy – axonal neuropathy. Some segmental demyelination.
• Endoneurial arterioles show hyalinization, BM thickening.
• Neuropathies catergorised as: distal symmetric sensory (or sensorimoto) neuropathy, autonomic neuropathy & focal (or multifocal) asymmetric neuropathy.
• Symmetric neuropathy affecting distal sensory and motor nerves common neuropathy. Autonomic neuropathy also common.
Clinical Presentation
• Type I – younger (20 and below age at presentation.
• Triad of P – polyuria, polyphagia and polydypsia.
• Ketoacidosis – nausea, vomiting, respiratory symptoms
• Ketoacidotic coma• Hypoglycaemic coma
Clinical Presentation
• Type II – older age group. 30+. Usually obese.
• Triad of Ps. • Routine medical check – common
way to diagnose. Asymptometic. Unaware.
• Hyperosmolar nonketotic coma.• Infection and septicaemia• Other complications – AMI, foot
ulcer, cellulitis etc
Laboratory Diagnosis
• Elevated blood glucose: non-fasting fasting >11.1 mmol/L; Fasting of >7.1 mmol/L.
• Oral glucose tolerance test.• HBA1C – monitoring of control of
blood glucose level.