Type 1 Diabetes Mellitus

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Type 1 diabetes mellitus results when the beta cells of the islets of Langerhans are progressively destroyed by autoimmune attack. Recent evidence in mice suggests that killer T lymphocytes (chapter 15) may target an enzyme known as glutamate decarboxylase in the beta cells. This autoimmune destruction of the beta cells may be provoked by an environmental agent, such as infection by viruses. In other cases, however, the cause is currently unknown. Removal of the insulin-secreting beta cells causes hyperglycemia and the appearance of glucose in the urine. Without insulin, glucose cannot enter the adipose cells; the rate of fat synthesis thus lags behind the rate of fat breakdown and large amounts of free fatty acids are released from the adipose cells.

In a person with uncontrolled type 1 diabetes, many of the fatty acids released from adipose cells are converted into ketone bodies in the liver. This may result in an elevated ketone body concentration in the blood (ketosis), and if the buffer reserve of bicarbonate is neutralized, it may also result in ketoacidosis. During this time, the glucose and excess ketone bodies that are excreted in the urine act as osmotic diuretics (chapter 17) and cause the excessive excretion of water in the urine. This can produce severe dehydration, which, together with ketoacidosis and associated disturbances in electrolyte balance, may lead to coma and death (fig. 19.11).

Clinical Investigation Clues

Remember that Phyllis did not have glycosuria when she gave a sample of urine to the physician.Yet she also complained of frequent urination and continuous thirst.

What might cause Phyllis to have glycosuria at other times, which didn't show up in the urine sample?

Could Phyllis have ketonuria?

What might be the cause of her frequent urination and continuous thirst?

In addition to the lack of insulin, people with type 1 diabetes have an abnormally high secretion of glucagon from the alpha cells of the islets. Glucagon stimulates glycogenolysis in the liver and thus helps to raise the blood glucose concentration. Glucagon also stimulates the production of enzymes in the liver that convert fatty acids into ketone bodies. The full range of

Regulation of Metabolism symptoms of diabetes may result from high glucagon secretion as well as from the absence of insulin. The lack of insulin may be largely responsible for hyperglycemia and for the release of large amounts of fatty acids into the blood. The high glucagon secretion may contribute to the hyperglycemia and in large part causes the development of ketoacidosis.

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