COMPLICATIONS OF DIABETES

COMPLICATIONS OF DIABETES

• Acute metabolic complications

  • Severe and acute metabolic complications of Type 1 diabetes is Diabetic ketoacidosis

  • In type 2 diabetes, higher portal vein insulin levels prevents unrestricted hepatic fatty acid oxidation

  • Patient develops hyperosmolar hyperosmotic syndrome due to severe dehydration

  • Second common acute complication is hypoglycemia usually as a result of missed meal, excessive physical exercise, an excess of insulin administration.

    • Signs and symptoms are

      • Dizziness, confusion, sweating, palpitations and tachychardia

      • If hypoglycemia continues there is loss of consciousness

• Chronic metabolic complications

  • Four distinct mechanisms have been implicated in the deleterious effects of persistent hyperglycemia on peripheral tissue

    • Formation of Advanced Glycation end products

    • Activation of protein Kinase C

    • Oxidative stress and disturbances in polyol pathways

    • Hexosamine pathways and generation of Fructose -6-phosphate

  • Macrovascular disease

    • The hall mark is accelerated atherosclerosis involving the aorta and large and medium sized arteries

    • Myocardial infarction caused due to atherosclerosis of coronary arteries is the most common cause of death in DM

    • Gangrene of the lower limb occurs in advanced vascular disease

    • Hyaline arteriosclerosis leading to hypertension

  • Microangiopathy

    • Diffuse thickening of the basement membranes of the small capillaries in the skin, skeletal muscle, retina, renal glomeruli and renal medulla

    • Thickening of basement membrane is by concentric layers of hyaline material composed predominantly of type IV collagen

    • These capillaries are more leaky and underlie the development of diabetic nephropathy, retinopathy and neuropathy

    • Diabetic nephropathy

      • Three lesions encountered in kidney  are

        • Glomerular lesions

        • Renal vascular lesions principally arteriosclerosis

        • Pyelonephritis including necrotizing papillitis

        The most important glomerular lesions are –

        • Capillary basement membrane thickening

          • Thickening of basement membrane of glomerular capillaries leads to diabetic microangiopathy

          • Thickening leads to mesangial widening

          • Thickening of BM of capillaries starts at as early as 2 years

          • Later thickening of tubular basement membrane occurs

        • Diffuse mesangial sclerosis

          • Lesion consists of diffuse increase in mesangial matrix

          • Initially there is mesangial proliferation but later mesangial increase is associated with overall thickening of GBM and matrix deposition of PAS positive material

          • As the disease progresses mesangial deposition takes nodular configuration

        • Nodular glomerulosclerosis ( kimmelstiel-wilson lesion )

          • Also known as “intercapillary glomerulosclerosis” or “Kimmelstiel-Wilson disease”

          • Glomerular lesions take the form of ovoid or spherical laminated nodules of matrix situated in the periphery of the glomerulus

          • Nodules are PAS positive and are surrounded by capillary loops

          • Nodular lesions are accompanied by accumulations of hyaline material in capillary loops or adherent to bowman’s capsules

          • As the disease advances individual nodules enlarge and compress capillaries, obliterating the glomerular tuft

          • Both afferent and efferent arterioles show hyalinosis

          • Later due to arteriole and glomerular lesions, kidney develops ischemia which leads to tubular atrophy, interstitial fibrosis and contraction in size of the kidney

    • Diabetic ocular complications

      • The ocular involvement may be in the form of –

        • Retinopathy due to neovascularization

        • Cataract formation

        • Glaucoma

    • Diabetic neuropathy

      • The most common neural complications are –

        • Peripheral neuropathy

        • Autonomic neuropathy

Reference 

1. Anirban Maitra. The Endocrine system.In: Robbins and Cotran Pathologic basis of disease.9th edition.volume II.chapter 24. pp 1073-1141.