COMPLICATIONS OF DIABEETUS

Liberty Medical

Microvascular and Macrovascular

27.8

22.9

18.9

9.8 9.5 9.17.9

6.66.1

10

1.8 1.7 2.11.1 1.8

0

10

20

30

Chronickidneydisease

Footproblems

Eye damage MI Chest pain CHD CHF Stroke

Pa

tie

nts

(%

)

Diabetes

Normal glucose levels

Pathogenesis Formation of Advanced Glycation End Products (AGEs)

Glucose byproducts react with IC and EC proteins AGEs bind RAGE receptor (Inflammatory cells, endothelium,

vascular smooth muscle)○ Increase inflammation, ROS, procoagulant activity

AGEs also cross link collagen○ Decreases elasticity of vessels○ Helps trap LDL and Proteins (albumin)

Activation of PKC IC hyperglycemia stimulates PKC and DAG

○ Pro-inflammatory, pro-fibrinolytic○ Increases endothelin 1 and decreases NO○ Increase VEGF (neovascularization in diabetic retinopathy)

Pathogenesis (cont.) Intracellular Hyperglycemia

Nerves, Lenses, Kidneys and BV uptake glucose without help of insulin

Excess Glucose Sorbitol Fructose○ Uses Aldolase Reductase ○ Uses NADPH

Reduces NADPH needed to regenerate glutathione (an antioxidant)

May be major underlying cause of Diabetic Neuropathy

Macrovascular

Endothelial Dysfunction HTN CVA, Hemorrhage Accelerated Atherosclerosis

All arteries incl. large renal arteries CAD/CHF/MI

Coronary atherosclerosisMost common cause of death

Gangrene of the Lower Extremities

Diabetic Nephropathy

Leading Cause of End-Stage Renal Disease

20 years: 75% of type I and 20% of type II

Starts as Microalbuminuria and progresses to macroalbuminuriaMarker for increase CV morbidity

Diabetic Retinopathy

60-80% Result of Neovascularization

Also: Increased risk of glaucoma and cataract formation

Diabetic Neuropathy

Variety of clinical syndromes Most Common: Distal Symmetric

PolyneuropathyDecreased motor and sensory function

particularly of distal lower extremitiesEventually involve upper extremities

Autonomic NeuropathyBowel, bladder and sexual dysfunction

Diabetic MononeuropathyEx. Wrist or foot drop; isolated CN palsy

Infections

Immunosupressed StateTBPneumoniaPyelonephritis

Many reasons (decreased neutrophil function, impaired cytokine production, vascular compromise)

5% of deaths

Resources

Robbins