Complications of Diabetes Mellitus Dr Rodney Itaki Lecturer Anatomical Pathology Discipline University of Papua New Guinea School of Medicine & Health Sciences Division of Pathology

Clinical approach to Complications of DM Acute Complications  Ketoacidosis (Type I DM)  Hyperglycemic hyperosmolar non-ketotic syndrome (Type II DM)  Hypoglycaemia Chronic 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

Non-enzymatic Glycosylation of Proteins Ref: Robins Pathological Basis of Diseases, 6 th Ed.

Biological Properties of AGE Ref: Robins Pathological Basis of Diseases, 6 th Ed.

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, 6 th 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 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.

Prognosis Most patients die from –AMI –Chronic renal failure –CVA –Infections.

End Main Reference: Robins Pathological Basis of Diseases, 6 th Ed. Chapter on The Pancreas. Download PPT notes on: