Diabetes mellitus. Etiology & pathogenesis. Pathomorphology of organ-site alterations. Complications.
Diabetes is a group of metabolic disorders that share the feature of hyperglycemia as a result in defects from insulin secretion, insulin action or both. Chronic hyperglycemia can cause secondary damage to the kidneys, eyes, nerves and blood vessels.
Diagnosis is based on one of the three:
- Random blood glucose concentration of 200 mg/dL or more with classic symptoms
- Fasting glucose of 126 mg/dL or more
- Oral glucose test of 200 mg/dL or more
Classification of diabetes is as follows:
- Type 1 - absolute deficiency of insulin due to pancreatic beta cell destruction due to autoimmune attack
- Type 2 - peripheral insulin resistance and inadequate compensatory response of insulin secretion
Type 1 pathogenesis
- Autoimmune destruction of beta pancreatic cells
- Develops in childhood and becomes manifest at puberty, while onset is abrupt, underlying pathogenic process has being going on for some time
- Failure of self tolerance in T cells due to inherited variants of HLA-D genes that encode class II MHC
- Additionally, environmental factors such as infections may be involved, specifically mumps, rubella and coxsackie B
Type 2 pathogenesis
- Complex multifactorial disease with environmental factors such as diet and exercise play a role along with genetic factors.
- There is decreased ability of peripheral tissues to respond to insulin and beta cells become ‘exhausted’ from trying to produce the required amounts for the body, meaning that beta cell dysfunction occurs as well.
- Insulin resistance is tightly linked to obesity
Organ site alterations and complications
General complications
- Macrovascular disease
- Diabetes rapidly increases rate of atherosclerosis
- Hyaline arteriosclerosis
- Hyaline is found deposited into the vessels
- Microangiopathy
- Diffuse thickening of basement membranes throughout the body is visible, this is most evident in capillaries of the skin, muscles, retina and renal glomeruli.
- It is this thickening which underlies the development of diabetic nephropathy, retinopathy and neuropathies
Specific organ damage
- Pancreas
- Reduction in number and size of islets
- Leukocytic infiltration of the islets
- Amyloid replacement of islets (long standing type 2)
- Eye
- Retinopathy
- Cataracts
- Glaucoma
- Brain
- Microangiopathy
- Cerebral vascular infarcts
- Hemorrhage
- Heart
- Myocardial infarction - most common cause of death in diabetics
- Kidneys (Diabetic nephropathy)
- Another common cause of death in diabetics, three lesions are encountered
- Glomerular lesions
- Renal vascular lesions
- Pyelonephritis (inc necrotizing papillitis)
- The most important pathogenic process causing these lesions is the thickening of the capillary basement membrane
- PNS
- Peripheral neuropathy
- Limbs
- Ischemic gangrene due to peripheral vascular atherosclerosis