Late Complications of Diabetes

  • Circulatory Abnormalities:
    • Atherosclerosis: more extensive and occurs earlier (accelerated course)
      • Lesions initiated by oxidized LDL
    • Increased platelet adhesiveness
    • Increase secretion of endothelin-1
      • Endothelin-1:powerful vasoconstrictor; vascular smooth muscle mitogen
    • Decreased nitric oxide production:
      • Nitric oxide: vasodilator; anti-mitogenic in vascular smooth muscle
    • Diabetes: procoagulant state--
      • increased levels of tissue factor
      • deficiency of tissue factor pathway inhibitor type 1
      • factor VIII elevated
      • impaired fibrolysis: (probably as a result of increased tPA inhibitor, type 1)
    •  Symptoms:
      • Intermittent claudication, gangrene, impotence (vascular)
      • Coronary artery disease; stroke:common
      • Silent myocardial infarction

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  • Retinopathy:
    •  Diabetic retinopathy: leading cause of blindness in the U.S.
    • Retinopathic lesions:
      1. simple (background)
      2. proliferative
    • Progression:
      • Increased capillary permeability
      • Retinal capillary occlusion (saccular and fusiform aneurysms)
    • Vascular lesions associated with:
      • Proliferation of lining endothelial cells
      • Pericyte loss around vessels
    • Proliferative retinopathy: new vessel formation and scarring.

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  • Diabetic Nephropathy
    •  Renal disease: leading cause of death and disability due to diabetes.
    • 50% of end-stage renal disease in United States: diabetic nephropathy
    • Complication rates:
      • 35% of IDDM patients
      • 15 to 60% of NIDDM patients (ethnic background dependent; highest -- Pima Indians;lowest- Europeans)
    • Two pathologic patterns:
      • diffuse-- more common
        • widening of glomerular basement membrane
        • menangial thickening
      • nodular
        • periodic acid-Schiff-positive material: deposited at glomerular tuft periphery
        • hyalinization of afferent and efferent arterioles
        • deposition of albumin and other proteins in tubules and glomeruli

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  • Diabetic Neuropathy
    • Major cause of morbidity
    • Peripheral Polyneuropathy: most common
      • bilateral, characterized by:
        1. numbness
        2. paresthesias
        3. severe hyperesthesias
        4. pain (deep-seeded, severe)
    • Mononeuropathy: characterized by --
      • wrist drop
      • foot drop
      • paralysis of third, fourth or sixth cranial nerve
    • Radiculopathy:
      • Sensory syndrome: pain -- distribution of one or more spinal nerves -- usually in chest wall or abdomen
    • Autonomic neuropathy:
      •  Significant target: gastrointestinal tract -- symptoms include:
        • esophageal dysfunction
        • delayed gastric emptying
        • constipation or diarrhea
      •  Orthostatic hypotension
      •  Syncope
      •  Cardiopulmonary arrest; sudden death
      •  Bladder dysfunction (may require chronic catheter drainage)
      •  Impotence/retrograde ejaculation
    • Treatment:
      • Pain: if severe, codeine -- drug of choice -- other options:
        • phenytoin
        • combination treatment with amitriptyline and fluphenazine

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  • Diabetic Foot Ulcers:
    • Secondary to diabetic neuropathy: abnormal pressure distribution
    • Vascular disease (decreased perfusion): augments ulcer development
    • Infection: common (multiple organisms)
      • Initial antibiotic treatment (until culture results are available):
        • ampicillin-sulbactam plus gentamycin or aztreonam
  • Autonomic Dysfunction:Diabetes Mellitus:
    • initial finding: often asymptomatic abnormal vagal function (reduced heart rate variation with deep breathing)
      • Loss of myelinated and non-myelinated small nerve fibers in splanchnic distribution, carotid sinus, and vagus nerve
    • Enteric neuropathy:
      • disturbances and gut motility
      • nausea/vomiting
      • achlorhydria
      • bowel incontinence
    • Other Symptoms:
      • impotence
      • urinary incontinence
      • pupillary abnormalities
      • postural hypotension
      • symptoms of hypoglycemia -- blunted or detectable because damage to sympathetic adrenal gland innervation prevents epinephrine release
      • Autonomic dysfunction may lengthen Q-T interval -- associated with sudden cardiac death

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Foster, D. W., Diabetes Mellitus, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2074-2077