Understanding what happens in the body?

Pathophysiology of Diabetes Mellitus

The exact mechanism involved in the development of Diabetes mellitus remains unclear. When a deficiency exists in amount or activity of insulin, hyperglycemia results and hyperglycemia (elevated serum blood glucose) is diabetes. This lack of insulin can be absolute, when the pancreas does not produce enough insulin or produces none at all, as is seen in insulin dependent diabetes mellitus. Alternately, the lack can be relative, when the body produces normal amounts of insulin, but for some reason that amount is not enough or the insulin is ineffective. That is, insulin resistance is present, as seen in non insulin dependent diabetes mellitus (NIDDM). These absolute or relative insulin deficiency results in significant abnormalities in the body fuels. The body needs fuel for all its functions, for building new tissue, and for repairing tissue. The fuel comes from the food that is ingested, which is composed of carbohydrates, proteins, and fats. It is important to understand and emphasize that diabetes is not a disease of “sugar’ alone, although the diagnostic criteria that have been devised to use the serum glucose level as the marker for the diagnosis and control of the disease. 

A relative or an absolute lack of insulin results in hyperglycemia and impaired fat metabolism. After a meal, due to the deficiency in the action or amount of insulin, glucose is not taken up from the portal vein by the liver. Thus, glucose remains in the general circulation, and glycogenesis (formation of glycogen from glucose) is inhibited. In addition, due to cellular starvation, the liver continues to produce glucose and to release this glucose into the blood stream. These processes worsen the hyperglycemia.

Amino acid transport into muscles cells also requires insulin; thus amino acid uptake and protein synthesis in muscles are impaired. The metabolism of triglycerides, fatty acids, and glycerol is altered. Instead of formation of triglycerides, breakdown occurs. The liver will continue the formation of or increase the formation of ketone bodies from fatty acids.

These alterations in metabolism result in glycosuria (sugar in the urine) because the blood glucose level reaches the renal capacity/threshold (approximately 180 mg/dl) in functional and normal kidneys. At this point the kidney cannot keep up with reabsorbing the glucose from the glomerular filtrate. Glucose draws and attracts water, and osmotic diuresis eventually occurs, thus polyuria (increased urination) occurs. This polyuria will result in the loss of water and electrolytes, particularly sodium, chloride, potassium, and phosphate. The significant loss of water and sodium results in thirst and increased fluid intake (polydipsia). Extreme hunger and increased food intake (polyphagia) are triggered persuant to cell starvation. In IDDM, this vicious cycle of a glucose cycle of glucose loss leads to calorie loss and weight loss. The lack of nutrients to cell leads to fatigue and lethargy.

The altered metabolism results in changes in serum laboratory data. This includes the following:

• Abnormalities in serum glucose and serum lipid levels

• Serum cholesterol is elevated

• Total body levels of electrolytes (sodium, potassium, chloride, phosphate) can be depleted, although serum levels may be elevated because of dehydration.

The severity of the altered metabolism depends on the severity of the absolute or relative insulin deficiency. If the alterations just described are not corrected or adequately controlled, acute and chronic complications can occur.