Overview of Chronic Complications of Diabetes Mellitus:

• Chronic high blood glucose causes degenerative damage throughout the body over time.
• Significant risk of vascular damage, leading to atherosclerosis, and damage to eyes, kidneys, and nerves.

Vascular Damage and Atherosclerosis:

• Chronic high blood glucose and hyperlipidemia contribute to blood vessel wall deterioration making blood vessels susceptible to the development of
  • arteriosclerosis (narrowing and loss of elasticity) and
  • atherosclerotic plaque formation (also narrows the lumen of blood vessels).

• Damage occurs in small (microvascular) and large (macrovascular) vessels.

• • Narrowed blood vessels contribute to high blood pressure. 
  • Blood vessel narrowing leads to ischemia in tissues and organs.
    • Less functional tissue.
    • Tissue necrosis in severe cases.

• Hyperglycemia leads to endothelial cells lining the inside of blood vessels becoming dysfunctional, specifically because:
  • 1. High glucose induces endothelial cell mitochondria to produce high levels of ROS (Reactive Oxidative Species), which overwhelm the endogenous neutralizing antioxidants.
       1. ROS cause damage to cellular proteins, DNA and plasma membranes)
    2. High glucose in endothelial cells leads to excessive glycation of cellular proteins, leading to toxic waste build-up.
    3. High glucose reduces the ability of endothelial cells to synthesize the vasodilator NO (nitric oxide).
    4. High glucose reduces the ability of endothelial cells to phosphorylate NO synthase.
  • Without the ability to produce NO, blood vessels are not able to conduct normal autoregulation (e.g., vasodilate regionally in response to increased blood volume and blood pressure).

• Lipolysis due to diabetes results in high blood lipids, increasing risk for atheroma formation.

Vascular Damage – Possible Complications:

• Large blood vessel damage:
  • Often worsened by hypertension.
  • Coronary arteries and brain arteries are affected.
  • Leads to peripheral vascular disease and risk of cerebrovascular accidents (CVA, strokes).

• Peripheral vascular disease can cause risk of limb ischemia and gangrene:
  • Claudication (pain with exercise) signals insufficient oxygen in muscles.
  • Severe cases may require amputation to prevent gangrene and further infection.
  • Delayed wound healing and infection susceptibility are common due to poor blood flow.
  • Cyanosis may develop due to hypoxia and ulcers may lead to amputation.

• Affects small vessels in the retina, kidneys, nerves, and skin.

Neurons:

• Rely heavily on steady blood flow.
• Ischemia causes neuronal dysfunction and death.
  • Ischemia results in demyelination, loss of function, sensory, motor, and autonomic fibers.
• Peripheral neuropathy:
  • Loss of sensory gives rise to paresthesia (e.g., numbness, tingling, loss of sensation).
  • Loss of motor neurons gives rise to muscle weakness.
  • Autonomic nerve damage can cause impotence and bladder dysfunction.
• Nerve death can accompany ulcers and poor wound healing, especially in the feet.

Vision Impairments:

1. Retinal microvascular damage leads to:
   • Retinopathy: Damage to tiny retinal blood vessels produces:
     • Microaneurysms: weakening and bulging of vessel walls.
     • Hemorrhages: Bleeding into the retina.
     • Neovascularization: formation of new, fragile blood vessels that can rupture and cause scarring.
     • Progression:
       • Neuron death in the retina and formation of scarring which distorts the retina.
       • Possible Retinal detachment, which is a medical emergency (as retina tears away from vascular tunic (layer of the eyeball), leading to ischemia of the torn portion of the retina.
         • Neurons in the retina will die if deprived of oxygen and nutrients for long, making retinal reattachment a pressing necessity.
       • Blood and debris can float in the vitreous humor, causing floaters and impairing vision.
       • Retinopathy causes visual impairment and blindness.
   • Treatment:
     • Photo-coagulation: Laser treatment to seal off leaking vessels.
     • Retinal detachment is an emergency requiring surgical intervention.
     • Replacing the vitreous humor with artificial material is used to fix problems with floaters.
2. Edema and Macular Damage:
   • Macular edema causes swelling in the central retina.
   • Results in distorted vision.
   • Progressive damage can lead to blindness.
3. Diabetic Cataracts
   • Diabetic cataracts develop from glucose accumulation in the lens, especially sorbitol.
   • Water drawn into the lens causes swelling and opacity, impairing vision.
   • Cause blurry vision.

• • Preventative measures:
    • Tight blood glucose control.
    • Use of sunglasses.
    • Cataract surgery if necessary.

Kidney Damage (Nephropathy):

• Diabetes accounts for 40% of end-stage renal failure.
• Damage occurs in glomeruli and nephrons, leading to:
  • Scarring.
  • Loss of glomerular filtration rate.
  • Renal failure.
• Additional factors:
  • Hypertension worsens renal ischemia.
  • Electrolyte imbalances from polyuria can affect the heart and muscles.
  • Infections in urinary tract due to glucose-rich environment.

Summary

• Chronic high blood glucose damages blood vessels, neurons, and organs.
• Retinopathy causes vision loss via microvascular damage.
• Diabetic cataracts cause blurry vision
• Macular edema contributes to vision loss and blindness.
• Macrovascular disease increases risk of hypertension and cardiovascular events (e.g., heart attack), stroke, and renal failure.
• Infection susceptibility increases due to vascular and immune system impairments.
• Preventing and managing vascular and neural complications are critical.
• Early detection and management are essential to prevent severe vision loss and tissue necrosis.
• Possible Complications include: Hypoglycemia (insulin shock) and DKA, which are acute, life-threatening events.
• Regular screening, tight blood glucose control, and early intervention improve outcomes.