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

Non-enzymatic Glycosylation of Proteins

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

Biological Properties of AGE

Ref: Robins Pathological Basis of Diseases, 6th 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, 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.

Prognosis

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

End

Main Reference: Robins Pathological Basis of

Diseases, 6th Ed. Chapter on The Pancreas.

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