Synopsis
Book by Alterman MD Seymour L Kullman MD Donald A
Extrait
Diabetes Mellitus: An Overview
Diabetes mellitus, or “diabetes” as it is commonly known, is a disorder of metabolism—the way our bodies use food to obtain energy. The most apparent disturbance in diabetes is with carbohydrate metabolism and is classically characterized by an elevated blood sugar and often the excretion of sugar in the urine. To understand diabetes, it is necessary to know how the body functions normally to convert food substances into energy. The human body may be thought of as a machine that requires “fuel” to function.
As we walk down the street, hit a baseball, or just take a breath, we expend energy. The body’s fuel is obtained from the food we eat—carbohydrates (sugars and starches), proteins, and fats. Food must be digested—broken down in the gastrointestinal tract—before it can be absorbed. Complex carbohydrates such as those in vegetables and whole grains are composed of long-chain molecules that are broken down by the digestive enzymes into their simple sugar components. All the simple sugars are eventually converted into glucose, the body’s main fuel, which is the form of sugar required by the body’s cells for energy. Proteins are broken down by the digestive enzymes into their constituent amino acids. Fats are digested to fatty acids.
Your body is comprised of billions of cells, the smallest units of living matter. Each cell is surrounded by a cell membrane that protects the inside of the cell from its environment. For glucose to get into the cells, where it can be used, it must cross this protective barrier. The hormone insulin, manufactured by specialized cells in the pancreas,* called beta cells, is secreted directly into the bloodstream and transported throughout the body, where it plays a vital role in the conversion of glucose into usable energy by escorting it across cell membranes. It is the key that opens the cell door to allow glucose in.
Once taken up by the tissues, glucose is either metabolized (burned) to supply the energy for all body functions or is stored away for future use to be drawn upon later when needed.
The pancreas secretes a steady, constant basal amount of insulin.
In a healthy person, rising blood sugar levels after eating serve as a signal for the pancreatic beta cells to secrete insulin. The beta cells act like a tiny thermostat, constantly measuring the blood sugar and releasing precisely the right amount of insulin to ensure the correct balance between the blood glucose level and the quantity of insulin needed to metabolize the glucose and keep the blood sugar within a fairly narrow range. When blood glucose levels are high, insulin helps muscle and liver cells respond to the body’s need to lower the blood sugar by removing glucose molecules from the blood and stringing them together to form long, complex molecules, called glycogen—an efficient form for glucose storage in the muscles and liver. Glucose that is not used by the body or exceeds its capacity for glycogen storage is converted into triglycerides—a storage form of fat.
The liver may be thought of as a food processing center. Insulin enables the liver to not only convert glucose into glycogen, but also to synthesize, from amino acids, proteins that the body needs for cell growth and repair. Any surplus amino acids are converted by the liver into glucose or glyco-
*The pancreas is a flat abdominal organ situated in the posterior abdomen below and behind the stomach. It functions as though it were two organs. As a digestive organ, it secretes enzymes into the intestinal tract that help to break down food into constituents that the body can use. As an endocrine organ, it secretes insulin and other hormones into the bloodstream that regulate the metabolism of glucose, proteins, and fats. Normally, in non-diabetic persons, the pancreas can store approximately 200 units of insulin and it secretes about twenty-five to forty units daily to meet metabolic needs.
gen, depending on bodily needs. This process of manufacturing glucose from non-carbohydrate food sources, known as gluconeogenesis, helps the body function efficiently as it prevents any excess fuel from being wasted. Any carbohydrate or protein intake that exceeds the body’s immediate energy needs and glycogen storage capacity is rapidly converted by the body—with an efficiency greater than any machine—into fat and stored away. Thus, any of the body’s three sources of fuel—carbohydrates, protein, or fat—can end up as body fat. This explains why one gains weight, regardless of the type of food consumed, when the caloric content of the diet exceeds the caloric expenditure by the body.
After a full meal, the insulin-producing beta cells of the pancreas secrete adequate amounts of insulin to transport the glucose from the bloodstream into the cells, thereby keeping the blood sugar level from rising too high. Between meals—during the fasting state—blood sugar levels gradually decline, as do blood insulin levels. However, should the blood glucose level fall too low, the alpha cells, another group of specialized pancreatic cells, secrete a hormone, glucagon, which acts in an opposite or antagonistic manner to insulin. Glucagon raises the blood sugar by signaling the liver to break down its glycogen stores and release glucose into the bloodstream. Glucagon can also mobilize stored fat and muscle protein, which are then transformed by the liver into glucose.
The brain, our body’s most important organ, relies primarily on glucose for fuel. It has evolved its own glucose regulatory mechanisms to ensure an adequate, continuous fuel supply. A special glucose-monitoring sensor within the brain responds to rapid falls in the blood sugar level by stimulating the adrenal glands to secrete epinephrine, another insulin antagonist hormone. Epinephrine is responsible for causing many of the symptoms associated with mild episodes of hypoglycemia (low blood sugar).
There are two main types of diabetes mellitus. Type 1 diabetes arises from the destruction of the insulin-producing beta cells of the pancreas, which causes an absolute deficiency of insulin. Without daily injections of insulin to replace what their bodies cannot produce, type 1s are unable to survive. In type 2 diabetes, the pancreas produces insulin, but the body’s cells become resistant to its glucose lowering action—an inability to use it efficiently. Before future Type 2s develop diabetes, their bodies require extra insulin to keep their blood sugar within the normal range.This compensatory mechanism of increased insulin output by the pancreas may suceed in controlling the blood sugar for years. However, over time, as insulin resistance gradually increases and the tired, overworked pancreas’s output of insulin decreases, the blood sugar rises—initially to levels beyond normal but below those needed to make a diagnosis of diabetes, the so-called impaired glucose tolerance phase. Eventually, the blood sugar rises to diabetic levels and the patient becomes symptomatic.
In type 2 diabetes, the body manufactures the insulin keys, but many of the cell door locks (insulin receptors) are blocked or defective, which prevents the insulin keys from doing their job.
Historical Perspective
Diabetes is an ancient disorder, recognized by its symptoms as early as 1500 B.C. in an Egyptian medical text called the Ebers Papyrus. In the second century A.D., Aretaeus, a Greek physician, gave the disease its present name from a Greek word meaning “to run through a siphon” (originally referring to the large volume of urine excreted in uncontrolled diabetes). The Latin word for honey, mellitus, appeared much later, and was employed to describe the honeylike odor and sweet taste of the urine. In 1775, Matthew Dobson, an Englishman, proved that the sweet taste of the urine of diabetics was actually due to sugar. In the 1860s, a medical student, Paul Langerhans, identified the patches of unique cells, scattered as small islands throughout the pancreas, which now bear his name. In 1889, two German physiologists, Drs. Von Mering and Minkowski, were the first to note that removal of the pancreas caused the syndrome known as diabetes mellitus. It was later demonstrated that the Islets of Langerhans actually manufactured, stored, and released the hormone insulin into the bloodstream.
For centuries, the symptoms of diabetes—marked thirst, frequency of urination, and weight loss—were well known. As the disease progressed, patients would try the various nostrums of the day: special diets, fasting, opium, barley water, and even blood-letting. Of course, these therapeutic efforts were to no avail because the real culprit was an absolute or a relative absence of the hormone insulin. As recently as the first two decades of the 1900s, there was no unanimity of medical opinion about the type of diet and medications that should be prescribed for diabetics. Most physicians speculated that a low carbohydrate diet would be beneficial. However, some believed that the sugar lost in the urine should be replaced and, accordingly, recommended a high carbohydrate diet. The guesswork treatment of diabetes came to an abrupt end in 1921 when a young surgeon, Frederick Banting, with the assistance of Charles H. Best, a medical student working in the physiology department at the University of Toronto, made an extract of the tiny pancreatic islet cells. When injected into laboratory animals, the extract caused a dramatic fall in blood sugar levels. Soon, human patients with diabetes were given this “new insulin treatment,” and the modern era of what had been a long and dismal history of diabetes treatment was to begin. Dr. Banting received the Nobel Prize for this important discovery.
Purification and standardization of insulin was undertaken, and prolongation of its action was finally achieved by adding proteins and zinc to the insulin extracted from animals, primarily cows and pigs. Today we use “human” insulin made semisynthetically from pork insulin, or biologically engineered, utilizing complicated recombinant-DNA technology. This has been of great value in reducing the allergic reactions that were sometimes seen with animal insulins.
In later chapters, we shall take an in-depth look at the different types of insulin and their use, as well as oral anti-diabetic medications.
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