Diabetes Over View

Understanding diabetes

The Disorder And The Diagnosis

Blood sugar, or blood glucose, refers to the amount of sugar in the blood. The brain's only food is glucose; therefore, blood sugar must be maintained at a certain level for the brain to function normally. After eating any meal that contains carbohydrate or protein, a person's blood sugar normally rises, often to between 120 and 130 milligrams per deciliter (mg/dL), but generally not above 140 mg/dL. Every day, every hour, blood sugar levels vary, even in people who don't have diabetes.

If the blood sugar level drops too low (a condition known as hypoglycemia), a person's ability to reason can become impaired. When the blood sugar levels are too high (a condition known as hyperglycemia), diabetes is diagnosed. Often the diagnosis is obvious to doctors because symptoms such as thirst, fatigue, weight loss, frequent urination, and persistent vaginal infections in women are evident. In the presence of these symptoms, diabetes can be confirmed by a random test of blood sugar, meaning that the blood is drawn at any time during the day, rather than specifically before eating breakfast. If the person is thirsty and urinating large amounts, the blood sugar usually will be well over 200 mg/ dL, sometimes up in the 300s and 400s or higher.

But when the classic symptoms are not present, the criteria for diagnosing diabetes include a fasting blood glucose test. This means that the blood glucose is drawn at least 10 hours following a meal early in the morning, when it is usually at its lowest point in the day. A random blood glucose higher than 200 mg/dL and a fasting glucose of 125 mg/ dL or more confirms a diagnosis of diabetes.

The Role of Insulin

Insulin is a hormone made in the pancreas, a large, elongated gland located behind the stomach. Its purpose is to "unlock" the cells of the body so that glucose carried by the blood can be used for energy. When you eat carbohydrates, your blood sugar rises. This increase triggers a release of insulin from cells in the pancreas called beta cells. The insulin "opens the doors" of the cells throughout the body to glucose. As glucose enters the cells, the blood sugar level falls back to normal - and the release of insulin ebbs until the next time proteins or carbohydrates are eaten.

The basic problem in type 1 diabetes is that the pancreas quits making insulin. In type 2, it either doesn't make enough or something interferes with the action of the insulin that is made. Someone with type 1 diabetes must inject replacement insulin to stay alive. Blood sugar levels in type 2 diabetes are usually controlled by drugs that lower blood sugar, diet and exercise. Sometimes, injections of replacement insulin are needed to maintain normal blood sugars.

The increasing emphasis on the importance of reducing weight and bringing about changes in lifestyles, combined with the latest advances in medical therapies have had dramatic effects on diabetes control.

Type 1 Diabetes

People with type 1 diabetes, such as 56-year-old Paul Keister of Arlington, Va.,* must inject replacement insulin to control the levels of glucose in their blood. Frequent tests (done several times a day) using blood obtained from finger pricks are required to control blood sugar levels.

In type 1 diabetes, the beta cells of the pancreas are destroyed by the body's immune system, which is responsible for recognizing and destroying external invaders such as viruses or bacteria.

In a process that is not very well understood by researchers and doctors, the body begins to think that its own pancreatic beta cells are "foreign" and sets off an "autoimmune" response that ends up destroying the cells. As a result, no insulin can be produced.

Type 1 diabetes accounts for 5 to 10 percent of all people with the disease. This type is sometimes called juvenile diabetes because it most commonly appears in children or adolescents. However, people older than 30 also may develop the condition.

Scientists believe that some environmental factor - possibly a viral infection or something related to nutrition, causes the immune system to destroy the insulin-producing cells. At 30, Keister was diagnosed with type 1 diabetes following a stomach illness and after a stubborn tooth infection refused to go away.

The resulting insulin deficiency is usually severe. Without injections of enough insulin to control increases in the blood sugar, diabetic ketoacidosis (coma and potentially death) can result. Today, type 1 diabetes is treatable, and ketoacidosis preventable by taking sufficient amounts of insulin and by following dietary guidelines set by doctors and the ADA.

Type 2 Diabetes

In this type, the pancreas continues to produce insulin; however, the body develops a resistance to its effects, resulting in a different kind of insulin deficiency. Although the blood sugar rises in type 2 diabetes for different reasons than it does in type 1, the symptoms and potential complications are similar.

Certain racial and ethnic groups, including African-Americans, American Indians, Mexican-Americans and other Hispanics, are at increased risk of diabetes. And obesity is a risk factor for type 2 diabetes. Although doctors don't know exactly why, they say it's clear that the muscle cells (where most of the sugar breakdown occurs) of obese people are far less responsive to insulin than are muscle cells of thinner people. An obese person's pancreas has to put out large amounts of insulin to keep blood sugars normal. The likelihood of developing type 2 diabetes in people who are at risk of it increases with age and weight gain.

The typical person with type 2 diabetes is older, overweight, and often has a family history of diabetes. But Dale Driscoll of Frederick, Md., was diagnosed with type 2 diabetes at about the same age that Paul Keister was diagnosed with type 1 - an indication that age alone is not a reliable diagnostic criterion. And there is little evidence to suggest that diabetes runs in Driscoll's family. There are exceptions to the general rule that diabetes occurring in the young is type 1, and that diabetes occurring in older people is type 2. Likewise, taking insulin does not mean you have type 1 diabetes, just as obesity is not a sure diagnostic sign of type 2.

According to experts, due to an increased number of older Americans and a greater prevalence of obesity and sedentary lifestyles, type 2 diabetes is nearing epidemic proportions in the United States.

Gestational Diabetes

Between 3 percent and 5 percent of pregnant women in the United States develop gestational diabetes - elevated blood sugar due to certain hormones, occurring only during pregnancy. It is important to diagnose and treat gestational diabetes properly because it increases the risk of a baby growing larger than he or she would have been. A large baby may mean a difficult delivery or a cesarean section. Keeping blood sugar within a normal range during the pregnancy reduces these risks. Women who experience gestational diabetes have a greater risk of developing diabetes later in life. One large study found that more than half of women who had gestational diabetes eventually developed type 2 diabetes.

Controlling Diabetes

Daily monitoring and careful control of blood sugar levels are the most important steps that people with diabetes can take, says David G. Orloff, M.D., director of the FDA's division of metabolic and endocrine drugs. Over the past decade, "tight control" of blood sugar with a goal of achieving and maintaining near-normal levels has become the standard of care for both type 1 and type 2 diabetes. "Maintaining normal levels is difficult", Orloff says, "but good glycemic control is the key to preventing long-term complications." Another reason for good blood sugar control", Orloff adds, "is that it does make a difference to how people feel."

Keeping blood sugars always between 150 mg/dL and 200 mg/dL, for instance, may help a person avoid obvious symptoms, but may not be good enough to avoid the long-term complications. Diabetes treatment is a complex approach that comprises a team of professionals, the patient, his or her family, and treatment and goals agreed upon by the team.

People with type 1 diabetes need insulin from the time they are initially diagnosed, throughout life. Type 2 diabetes may often mean a prescribed regimen of diet and exercise in the initial phases of the disease. Frequently, however, and certainly over time, changes in diet and exercise aren't enough to keep blood sugar at near-normal levels. The next step for these people is taking a medicine that lowers the blood sugar. There are two basic kinds: insulin therapy and oral medications.

Insulin Replacement Therapy

Before the availability of insulin, treatments for people with type 1 diabetes were unpleasant and often ineffective. A low- carbohydrate, semi-starvation diet and exercise were all doctors had to offer. People lost more and more weight, and many of them died within the first year of diagnosis. Like many scientific advances, the discovery of replacement insulin in the 1920s was nothing short of a miracle.

Insulin lowers blood sugar by both increasing the removal of glucose from the blood and reducing the production of glucose by the liver. In type 1 diabetes, since there is virtually no insulin produced by the pancreas, people need insulin all the time - more at mealtimes to "cover" the carbohydrates and protein eaten, and less during other times to maintain as even a level as possible. In people with type 2 diabetes, insulin injections sometimes are needed to supplement the amount produced by the pancreas.

Insulin injections are given under the skin (subcutaneously) into the fat layer, usually in the arm, thigh, or abdomen. Insulin cannot be given by mouth because the digestive enzymes in the stomach destroy it. Small syringes with very thin needles make the injections nearly painless. In recent years, several external insulin pumps, which deliver insulin continuously through a thin, flexible tube placed under the skin, have been developed.

Insulin Preparations

Since 1982, most of the newly approved insulin preparations have been produced by inserting portions of DNA ("recombinant DNA") into special lab-cultivated bacteria or yeast. This process allows the bacteria or yeast cells to produce human insulin. Recombinant human insulin has, for the most part, replaced animal- derived insulin, such as pork and beef insulin. More recently, insulin products called "insulin analogs" have been produced so that the structure differs slightly from human insulin (by one or two amino acids) to change onset and peak of action. The following table lists some of the more common insulin preparations available today. Onset, peak, and duration of action are approximate for each insulin product, as there may be variability depending on each individual, the injection site, and the individual's exercise program. There are more than 20 types of insulin available in four basic forms, each with a different time of onset and duration of action (see "Insulin Preparations," page 31). The decision as to which insulin to choose is based on an individual's lifestyle, a physician's preference and experience, and the person's blood sugar levels. Among the criteria considered in choosing insulin are: how soon it starts working (onset), when it works the hardest (peak time), and how long it lasts in the body (duration).

Oral Medications

Pills to treat diabetes - anti-diabetic agents - are used only in type 2 treatment. Four general classes of drugs work in different ways to lower blood sugar. There are some risks associated with the use of these drugs. For example, sulfonylureas, which stimulate the beta cells in the pancreas to release more insulin, can be associated with severe low blood sugar levels, particularly when the person has other medical problems or is taking other medications. And in order for them to work, a person's pancreas must be making at least some insulin. That is why oral medications will not work for the treatment of type 1 diabetes.

For best results, oral medications must be taken regularly every day, not irregularly or started and stopped according to blood sugar. Since many dosages are available, a physician can change the dosage if blood sugars are running too high or too low. Many of these drugs can be used in combination with one another, but any change in their use should be done only at the advice of a healthcare professional.

Medication or Insulin

Driscoll's doctor found that oral medications were not effective in controlling his blood sugar, and he replaced them with insulin injections. In retrospect, Driscoll says, "while the pills were easier to deal with, insulin has made the greatest difference in my life." In addition, Driscoll has shed 40 of the 100 pounds recommended by his doctor as part of his treatment plan.

Organ Transplantation

Pancreas transplants and kidney transplants are options for people with type 1 diabetes, if they have kidney failure (about one-third of type 1 patients). Since the 1970s, doctors have performed pancreas transplants along with kidney transplants in hopes of halting or reversing the complications of diabetes. The procedure has met with some success. Kidneys alone are transplanted to replace kidneys that have totally failed. Pancreas transplants may be done simultaneously or after kidney transplants, to try to "cure" diabetes. "But pancreases are often not transplanted unless a kidney is also needed", says Saudek, "because the surgery is so major and the need for continuous immune suppression is more dangerous than taking insulin." Saudek adds that unavailability of transplantable kidneys and pancreases also is a factor.

A kidney transplant for people with type 1 and type 2 diabetes can restore the body's ability to perform a number of crucial functions, including filtering wastes from the blood and controlling the body's fluid and chemical balance. Receiving a new pancreas at the same time may actually improve kidney survival. In addition, a new pancreas can improve blood sugar levels to normal, or close to it.

Organ transplants aren't always successful. Besides the risk inherent in any major surgery, the body can reject the new organ days or even years after the transplant. Because of this, transplant recipients will likely need to take immunosuppressive drugs the rest of their lives. The drugs \themselves carry significant health risks, such as cancer, but they work to prevent the immune system from rejecting the new organ.

Another noteworthy therapeutic intervention, and one that Keister hopes to be considered for, is a procedure called islet cell transplantation. Researchers have known for some time that transplanting these insulin-producing cells may provide a possible cure for type I diabetes. The process to date is still not perfected, but there is some evidence that researchers may be getting closer to their goal.

"From the biologics perspective," says Philip Noguchi, M.D., director of the FDA's division of cellular and gene therapy, "emphasis on products for diabetes is clearly experimental at this time, but potentially very promising." In islet cell transplantation, doctors extract islet cells from the pancreas of a person who has died recently and then infuse them via a catheter into the liver of the person with diabetes. The liver instead of the pancreas is the location for the transplant because it is easier and less invasive to access the large vein in the liver than a pancreatic vein, and islet cells that grow in the liver closely mimic normal insulin secretion.

Because the cells are very fragile, the procedure is fraught with problems. One of the biggest obstacles is the availability of fresh islet cells. Another challenge is the ability to isolate the cells. It takes several donor pancreases to isolate enough islet cells for a single transplant.

While additional studies are underway to learn more about the long- term effects of islet cell transplantation, Noguchi says, "at the moment there are a number of well-established procedures for type 1 and type 2 diabetes that let people live normal lives."

Prognosis

Outlook for people with diabetes can be excellent if the disease is well taken care of. Several major studies, including the Diabetes Control and Complications Trial Research Group, in which people with type 1 diabetes have been followed for years, compared the effects of standard and more intensive diabetes treatments on the development and progression of long-term complications. The more intensive treatments prevented or slowed diabetes complications.