Pathophysiological changes in Diabetes

•Diabetes is a disease characterized by either relative or absolute insulin deficiency leading to hyperglycemia.

•Absolute insulin deficiency as a result of autoimmune disease that destroys the pancreatic beta cells is associated with type 1 diabetes.

•Type 2 diabetes is associated with relative insulin deficiency and reduced tissue sensitivity to insulin (insulin resistance).

These changes in insulin function may lead to the following pathophysiological changes in the body:

✓High blood glucose level raises the osmolarity of blood making it more concentrated. This increased osmolarity leads to increased thirst (Polydipsia). 

✓High blood glucose levels induces frequent urination (polyuria) due to the osmotic pull of glucose on urine. The frequent urination is also caused by the excessive intake of fluids due to increased thirst.

✓High blood glucose leads to increased hunger, since the body is unable to adequately utilize glucose for energy. Additionally, glucose is lost in urine.

✓Diabetes can also cause weight loss due to breakdown of fats and proteins.

✓Hyperlipidemia which is the increase in the level of low density lipoproteins and reduced levels of high density lipoproteins occur mostly in type 2 diabetes. 

✓High blood glucose provides a source of nutrients for microbes which may lead to poor wound healing. Poor wound healing can progress to complications such as diabetic foot which is also aided by  peripheral nerve damage and damage to blood vessels. The complication may lead to limb amputation.

✓Diabetes may also cause nerve damage which manifests as numbness or tingling in arms and legs. Nerve damage may also affect autonomic functions leading to erectile dysfunction and difficulty in digestion or gastroparesis. 

✓Atherosclerosis. Accumulation of fat deposits on blood vessels. It is associated with cardiovascular complications such as narrowing of blood vessels and thrombosis. Damage to blood vessels also lead to other cardiovascular complications such as heart attack and stroke.

✓Diabetes may also lead to reduced supply of blood to the extremities of the body due to damage of blood vessels. This leads to complications such as peripheral vascular insufficiency which manifests as darkening of skin. 

✓Formation of Sorbitol. Sorbitol is formed when glucose is reduced. Sorbitol can get deposited on eye lens leading to cataracts and is associated with complications such as diabetic retinopathy which can progress to loss of vision (blindness).

✓Diabetes also leads to outflow of protein and albumin in urine (proteinuria and albuminuria). This may progress to complications such as renal failure (Diabetic nephropathy) which may require dialysis.

✓Formation of Ketones (Ketosis) which occurs when the body over-utilizes lipids for energy leading to formation of ketones (associated with type 1 diabetes). Ketones can lead to DKA (Diabetic ketoacidosis). Severe ketosis leads to DKA coma.

✓Extreme rise in blood glucose level where there is just enough insulin to suppress ketosis leads to non-ketotic hyperosmolarity. This is typical in type 2 diabetes where there is relative deficiency of insulin. The high blood sugar level leads to concentration of blood which may cause complications such as collapse of blood vessels and cardiovascular shock. This complication is known as Non-ketotic Hyperosmolar diabetic coma which is a medical emergency typical for type 2 diabetes.