9/21/2013

Etiology
Heredity is unquestioned as a prominent factor in the etiology of diabetes mellitus, although the mechanism of inheritance is unknown. Diabetes may be actually a syndrome rather than a specific disease. A variety of genetic mechanisms have been proposed, but most favor a multifactorial inheritance or a recessive gene somehow linked to the tissue-typing antigens, the human lymphocyte-A (HLA) system. However, the inheritance of non-insulin-dependent diabetes and insulin-dependent diabetes appears to be different. Nearly 100% of offspring pf parents who both have non-insulin-dependent diabetes develop that type of diabetes, but only 45% to 60% of the offspring of both parents who have insulin-dependent diabetes will develop the disease. There is also an increase risk of diabetes with obesity. The incidence of the disease doubles with every 20% of excess weight and this figure applies to the young as well as to the older diabetic person. Diabetes is now the sixth leading cause of death by disease in adults and the first leading cause of of new cases of blindness between 20 and 75 years of age. Viruses have been implicated on the etiology of diabetes. The viral theory states that the Beta-cells of some individuals (most specialists believe that the Beta-cells are genetically susceptible because of the defects in the HLA system) are attacked by certain viruses, causing cell damage or death. The body reacts to this damaged or changed tissue in an autoimmune phenomenon, forming antibodies that "attack" the Beta-cells, resulting in cell death. When there are not enough available Beta-cells to supply sufficient insulin to meet the needs of the body, insulin-dependent diabetes results. Tumors of the pancreas, pancreatitis, stress drugs as steroids, stress diseases that involve other endocrine organs such as acromegaly, heredity and viral diseases are now believed to play a part in causing diabetes.



In non-insulin-dependent, or type II, diabetes disturbed carbohydrate metabolism may be a result of a sluggish or insensitive secretory response in the pancreas or a defect in body tissues that requires unusual amounts of insulin, or the insulin secreted may be rapidly destroyed, inhibited, or in-activated in affected persons. A lack of insulin because of reduction in islet cell mass or destruction of the islets is the hallmark of the person with insulin-dependent, or type I diabetes.



Pathophysiology
Insulin is needed to support the metabolism of carbohydrates, fats and proteins, primarily by facilitating the entry of these substances into the cell. Insulin is needed for the entry of glucose into the muscle and fat cells, for the prevention of mobilization of fats from fat cells, and for storage of glucose as glycogen in the cells of liver and muscle. Insulin is not needed for the entry of glucose into nerve cells or vascular tissue. The chemical composition and molecular structure of insulin are such that it fits into receptor sites on the cell membrane. Here it initiates a sequence of poorly defined chemical reactions that alter the cell membrane to facilitate the entry of glucose into the cell and stimulate enzymatic systems outside the cell that metabolize the glucose for energy production.



With deficiency of insulin, glucose is unable to enter the cell and its concentration in the bloodstream increases, the increased concentration in the bloodstream increases. The increased concentration of glucose (hyperglycemia) produces an osmotic gradient that causes the movement of body fluid from the intracellular space to the extracellular space and into the glomerular filtrate in order to "dilute" the hyperosmolar filtrate. When the glucose concentration in glomerular filtrate exceeds the threshold (180mg/dL), glucose "spills" into the urine along with an osmotic diversion of water (polyuria), a cardinal sign of diabetes. The Urinary fluid losses cause the excessive thirst (polydipsia) observed in diabetes. As might be expected, this water washout results in a depletion of other essential chemicals.
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