Diabetes Introduction
A condition in which excessive amounts of some substances are excreted from the body. The term may refer to either of two unrelated diseases, diabetes mellitus and diabetes insipidus. The word diabetes derives from the Greek for siphon, a reference to the copious urine excretion that characterizes this affliction. In common usage, the term diabetes is synonymous with diabetes mellitus.
Diabetes Mellitus
Diabetes mellitus is a disease of abnormal carbohydrate metabolism in which glucose cannot enter the body’s cells and be utilized, and therefore remains in the blood in high concentrations. Mellitus is the Latin word meaning honey, and is applicable because the urine of patients with diabetes mellitus has a sweet taste, distinguishing this disease from diabetes insipidus, in which large volumes of dilute, almost colorless and tasteless urine are passed. In diabetes mellitus the excess sugar in the blood (hyperglycemia) leads to the excretion of sugar in the urine (glycosuria), a cardinal diagnostic symptom. Glycosuria in turn causes the
excretion of large amounts of urine (polyuria), which results in dehydration and intense thirst (polydipsia). Although blood glucose is high, it cannot enter the appetite-regulating cells of the hypothalamus; hunger is therefore great, and the diabetic person tends to eat constantly (polyphagia). But because glucose cannot enter and nourish the cells, body tissues are subjected to the equivalent of starvation; rapid weight loss occurs, part of which is due to the excretion of water in urine. See also: Carbohydrate metabolism
Varieties
Diabetes mellitus appears in two varieties, each with its own cause: diabetes mellitus type I (formerly known as juvenile onset diabetes), caused by deficiency of the pancreatic hormone insulin (whose chief function is to promote the entry of glucose into cells); and diabetes mellitus type II (formerly known as maturity onset diabetes), in which insulin is available but cannot be properly utilized.
Diabetes mellitus type I
Of the two forms of diabetes, type I is initially the more serious and less common, afflicting approximately 1 in every 600 children. The incidence varies among countries. The highest incidence is seen in Finland and Sweden, and some of the lowest in Korea and Mexico. The United States and Canada are included among the highest. Although it usually appears before the age of 20, type I diabetes can strike at any age. It is caused by a significant shortage or complete lack of insulin secretion. The endocrine cells normally responsible for insulin production are found in the pancreas, but have nothing to do with the ordinary digestive functions of that organ. They occur as islands of endocrine tissue, called islets of Langerhans, scattered throughout the substance of the pancreas.
The islets consist of at least three cell types, each of which secretes a different hormone important in regulating carbohydrate metabolism. The alpha cells produce glucagon, which elevates blood glucose; the beta cells produce insulin; and the delta cells produce somatostatin, a hormone that appears to participate in controlling the activity of the alpha and beta cells. In type I diabetes the beta cells are destroyed, possibly by the attack of the body’s own immune system or by virus infection; victims of type I require daily insulin injections to survive. Insulin must be injected rather than taken orally because it is inactivated by the enzymes of the digestive system. Without insulin therapy, a patient with type I diabetes will inevitably deteriorate into a condition of ketosis (presence in the blood of ketone bodies, the metabolic intermediates of fat metabolism) and acidosis (dangerously acidic blood pH).
Ketoacidosis, as the combined condition is called, leads rapidly to coma and death in the untreated diabetic. When Frederick G. Banting and Charles H. Best succeeded in purifying insulin from animal pancreatic tissue
in 1921, type I diabetics were given their first chance at living a normal life-span. Today type I diabetics are routinely treated by injections of insulin. Human insulin became increasingly available in the 1980s through the use of recombinant deoxyribonucleic acid (DNA) technology. In this technique the gene specifying human insulin is spliced into the chromosome of a bacterium, and the billions of progeny bacteria then produce insulin as though it were one of their own bacterial proteins, thus serving as minifactories for the hormone.
The bacterium used to produce insulin is Escherichia coli. Another DNA technique for producing insulin uses yeast instead of E. coli. Up to the early 1980s, insulin was extracted from cattle and pigs. This “foreign” insulin is still used, but has some unwanted side effects not seen or rarely seen with human insulin, therefore making human insulin the treatment of choice. One of the most important characteristics of insulin produced by genetic engineering, other than its being identical to human pancreatic insulin, is its limitless
availability. See also: Genetic engineering; Insulin; Pancreas
Diabetes mellitus type II
Type II is the more common form of diabetes mellitus, accounting for 8 out of every 10 cases. It usually appears after the age of 30, although an uncommon variant called type II diabetes of the young occasionally occurs in obese children and teenagers. The initial symptoms of type II diabetes are much less noticeable than those of type I, and the characteristic triad of polyuria, polydipsia, and polyphagia may even be entirely absent. For this reason, type II diabetes can exist undetected for dangerously long periods. Victims are not prone to the ketoacidosis and coma that threaten type I patients, and their disease can usually be managed without insulin injections. Thus two other names for type II diabetes are nonketosis-prone diabetes and non- insulin-dependent diabetes.
Whereas type I diabetes is a disease of insulin shortage, victims of type II diabetes usually have insulin in their bloodstream. In fact, insulin levels in type II diabetics are sometimes even higher than those in nondiabetic individuals. However, since the cells of a type II patient do not respond to insulin by taking in and utilizing blood glucose as normal cells would, the type II diabetic may have hyperglycemia in spite of high insulin levels. The probable reason for this defect is that the cells have specific receptor molecules on their surface membranes whose job is to recognize insulin and trigger the biochemical steps leading to glucose uptake and utilization. Interestingly, the number of insulin receptors on cells can be changed by gaining or losing body weight; the more body fat a person carries, the fewer insulin receptors there will be on the cells. This may explain why type II diabetes is mainly a disease of the obese, and why weight reduction is such effective therapy.
High glucose levels also decrease the number of insulin receptors; normalizing glucose levels is thus of utmost importance. The most important treatment for most cases of type II diabetes consists of exercise and weight reduction, which will return glucose metabolism to normal in 9 out of 10 cases. Because the cells of type II diabetics lack responsiveness to their own insulin, insulin injection therapy is used for some of these cases. Approximately 10% of all type II patients must use insulin.
This percentage appears to more than double in Black, Latino, Native American, or other minority patients living in the United States. In addition, a family of drugs known as oral hypoglycemic agents is often used in treating the disease. These drugs, including tolbutamide, chlorpropamide, acetohexamide, and tolazamide, lower blood glucose by stimulating the pancreatic cells to release insulin, and by augmenting insulin’s effect on the cells of the body.
All of these drugs are known as first-generation sulfonylureas. However, there are other drugs with the same basic molecule but with chemical changes in their structure; these are called second-generation sulfonylureas. This group of drugs is safe if properly used and is effective in many cases if used in conjunction with proper diet and exercise programs.
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