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Diabetes is a very serious disease in the U.S. affecting an estimated 16 million people, and is the sixth leading cause of death by disease. Diabetes is a metabolic disease that affects the body’s ability to use glucose (a simple sugar) as a source of energy. Recent developments in understanding the nature of diabetes has led to improved treatment methods that can lead to reductions in long term detrimental effects of the disease. Scientists hope to develop a vaccine or drug to prevent the destruction of pancreatic cells that occurs in insulin-dependent diabetes. The good news for people with an inherited susceptibility to non-insulin dependent diabetes is that they can help prevent it’s occurrence by adopting a lifestyle recommended by health professionals; a weight reduction program based on dietary changes and exercise.
Understanding and Treating Diabetes: New Developments
What is Diabetes?
Diabetes mellitus is an inherited disease that interferes with the process by which the body’s cells take up glucose and use it for energy. Carbohydrates (starches and sugars) in the diet are broken down by digestion into simple sugars, primarily glucose, which are then absorbed into the blood stream. The rising blood glucose levels stimulate the beta cells of the pancreas to secrete insulin. The insulin, in turn, stimulates body cells to take up insulin by attaching to “receptor sites.” When blood glucose levels return to normal, the pancreas no longer secretes insulin.
The more acute form of diabetes is now known as insulin-dependent diabetes or IDDM for short. Previously known as “juvenile onset”, since it usually appears before maturity, it constitutes only 5% of diabetes cases. In IDDM, the beta cells of the pancreas have been largely destroyed. As a result, little or no insulin is secreted. Without the insulin stimulus the cells cannot take up glucose, which then accumulates in the blood. In an attempt to obtain a source of energy, the cells begin to break down body proteins and fat. Unfortunately, this process leads to the formation of by-products called ketone bodies. If untreated with insulin, the patient can accumulate toxic amounts of ketone bodies, slip into a coma, and die.
What causes the pancreatic beta cell destruction found in insulin-dependent diabetes? We now know that IDDP is an autoimmune disease, in which the body’s own immune or disease-fighting system turns against its own beta cells. It appears that susceptible persons inherit genetic defects in their immune system. When the immune system is called into action by an environmental stimulus such as a particular virus infection, it can confuse the beta cells with the invader due to similarities in structure, and destroy them.
Non-insulin dependent diabetes, or NIDDM, is due to other causes. NIDDM was previously known as “adult onset” diabetes since it commonly does not occur until after the age of forty. It is commonly inherited. The majority of persons with NIDDM are overweight, especially in the abdominal region, which may bring on the condition. The outstanding feature of NIDDM is insulin resistance, which is a failure of the cells to respond to a stimulus of insulin. As a result, even though there is plenty of insulin circulating in the blood, the cells do not take up glucose, and its level in the blood begins to rise. In contrast to IDDM, the pancreas continues to produce insulin, although abnormalities in the beta cells and the rate of secretion of insulin may be noticed. In an attempt to secrete more and more insulin in response to rising glucose levels, the beta cells may eventually become exhausted.
Complications of Diabetes
The regulation of blood glucose levels by the body is an intricate and fine tuned affair. Until fairly recently, treatment of diabetes with insulin or drugs has not been completely successful in maintaining glucose levels within the normal range. The long-term detrimental effects seen in diabetes patients are a consequence of a lack of understanding of the dynamics of glucose regulation by the body, and the means to simulate these dynamics by medication.
Many theories have been brought forward to account for the detrimental effects on the body of long-term exposure to high blood glucose levels. Most recently, it has been shown that excessive glucose can eventually bind to the proteins of hemoglobin of the red blood cells as well as the blood vessels. The products that form can impair the normal functioning of these tissues. A different theory has been proposed to account for the damage to small nerves that also occur from exposure to high glucose levels. Often nerve and blood vessel damage go hand in hand to produce the long-term complications. If the affected vessels are large, it can lead to cardiovascular disease, stroke, and leg and foot disorders. If the affected vessels are small, it can cause kidney failure or eye complications possibly leading to blindness. These are long-term effects can take many years to develop.
Signs and Symptoms
The symptoms described below are characteristic of diabetes; however, a physician must be consulted for a definitive diagnosis:
Insulin-dependent diabetes:
The following symptoms may appear suddenly:
1.Frequent urination
2. Excessive thirst
3. Constant hunger
4. Extreme weight loss
5. Extreme fatigue
Non-insulin dependent diabetes:
May include any of the symptoms of IDDM, but generally occur more slowly and can be hard to detect.
The following additional symptoms suggest the onset of advanced complications:
1. Repeated or hard to heal infections of the skin, gums, bladder or vagina.
2. Blurred vision
3. Tingling or loss of feeling in the hands or feet
4. Heart disease
.
Prevention of Diabetes
Insulin-dependent diabetes:
Current knowledge is still inadequate to prevent the onset of diabetes in genetically susceptible individuals when exposed to environmental “triggers”. However, research has shown that the early application of insulin therapy can help to preserve some beta cell function and reduce the risk of long-term complications. Since IDDM is due to disorders in immune function, research has been directed toward developing a drug that would selectively bind to and inactivate the abnormal immune component, while retaining overall immune function.
Non-insulin dependent diabetes:
The best preventative measure for NIDDM susceptible individuals is to maintain normal weight through a program of proper diet and exercise. One should realize, however, that preventing overweight might be difficult to achieve in persons with a genetic propensity for obesity, which may be linked to a disposition for diabetes.
Treatment of Diabetes
Insulin
Patients with IDDM must receive insulin at least on a daily basis if they are to remain in good health. All insulin used to be derived by extraction from animal tissues. Since the body could detect this insulin as a foreign substance, some patients developed insulin resistance due to antibody formation. The recent introduction of genetically engineered human insulin has reduced the incidence of this type of problem.
Another product of genetic engineering is the use of insulin lispro, which acts more rapidly and with a shorter duration than human regular insulin. Insulin lispro improves diabetes management by better controlling the rapid rise in blood glucose following meals, and in reducing the incidence of hypoglycemia due to its shorter duration of action. The guidelines on its use in conjunction with regular insulin are still being developed.
For persons with NIDDM, insulin is usually not given unless a program of dietary changes, exercise and oral drugs fail to control blood glucose levels adequately.
Blood glucose monitoring
Recognizing the importance of maintaining normal blood glucose patterns, manufacturers began introducing home blood glucose monitoring kits in the late 1960’s. The procedure requires patients to prick their fingers several times a day in order to obtain blood samples for glucose testing. The results are used as a basis to determine insulin dosage.
A refinement of this technique is the recent development of the Continuous Glucose Monitoring System. This system detects glucose levels in tissues rather than blood, since tissue levels may represent a more sensitive measure of the potential harmful effects of diabetes. The method involves inserting a small needle under the skin in the abdomen to measure glucose. The data is evaluated by the physician in order to provide trends in glucose levels. The method is only a supplement to the ‘finger prick” testing.
Another development in this field has been the use of insulin pumps, which are placed either externally or internally in the abdomen area. The pumps deliver insulin in a closely controlled manner, and permits greater freedom in lifestyle for the patient, since blood glucose levels are more readily stabilized with fluctuations in food consumption and physical exercise.
Since finger pricking is not a very attractive procedure, efforts are underway to develop a non-invasive method of glucose testing. A new method on the horizon is the use of infrared technology, but it is not yet as accurate as finger-prick testing.
Pancreas transplants
Since the IDDM pancreas no longer produces insulin, efforts have been made to replace the damaged pancreas with a healthy one by transplantation. Although beneficial results for the first year after transplantation may be dramatic, it should be considered a temporary solution, as problems such as tissue rejection eventually appear.
Exercise
A recent symposium on “Exercise and the Insulin Resistance Syndrome” described how low intensity, prolonged exercise, such as a daily brisk walk of 45 minutes, has a remarkable ability to reduce insulin resistance, and thus help prevent (and treat) NIDDM.
Diet
There have been substantial modifications in the dietary recommendations for persons with diabetes in recent years. Currently, the American Diabetes Association recommends that people with diabetes follow the government’s Dietary Guidelines for Americans, and the Food Guide Pyramid. These guidelines indicate that carbohydrates should supply between 55% to 60% of total calories consumed, with only a maximum of 5% of calories to come from sugar. Emphasis is placed on the consumption of unrefined, fiber-rich carbohydrates such as those present in whole grains, legumes (beans, lentils), fruits and vegetables. When those foods are digested, there is a slower rise in blood glucose, reducing the burden on the pancreas to secrete insulin. Fat should be limited to 30% of energy needs, with saturated fat held to less than a third of that. Since persons with diabetes have a heightened risk for kidney disease, protein intake is limited to 0.8 gram per kilogram of body weight for adults.
The American Dietetic Association provides sophisticated methods of meal planning. One method uses exchange lists, which separate foods into six categories based on their nutritional makeup. Another method is called “carbohydrate counting,” in which grams of carbohydrate are monitored and adjusted according to blood glucose levels. Contrary to popular opinion, the Association recommends that total carbohydrate consumption should be the focus of consideration, not the type of carbohydrate, such as the avoidance of sugars.
Oral Medications for NIDDM Patients – These drugs are used when a program of exercise and dietary changes fail to control blood glucose. There are five classes of oral medications, and their choice of use can be a complex process. They are often used in combination.
Sulfonylureas – This class of drugs was introduced in the 1940’s, and development of new products has continued to this day. The chemical names of drugs in this class include chlorpropamide, tolazamide, tolbutamide, acetohexamide, glipizide, glimepiride and glyburide. These drugs act to reduce blood glucose by increasing insulin secretion by the pancreas, but not insulin production. Unfortunately, in some cases they can promote weight gain and hypoglycemia (a low blood sugar level condition that is potentially dangerous).
Megitinides – These drugs are related to the sulfonylureas, and include repaglinide. These drugs also act to increase insulin secretion, but are less prone to cause hypoglycemia.
Metformin – known under the trade name Glucophage, this drug appeared on the market in early 1995. It lowers blood glucose by a combination of reducing both glucose resistance by the cells and glucose production by the liver. It does not cause either weight gain or hypoglycemia. However, it has a potential problem of causing the condition of lactic acidosis that was previously discussed.
Acarbose – this medication, which is itself a carbohydrate, acts by inhibiting two enzymes involved in carbohydrate digestion. The result is a delay in the digestion of carbohydrates and absorption of glucose, resulting in a reduced rise in blood glucose. The most common adverse effects occur in the digestive tract, and include flatulence, diarrhea and abdominal pain. These effects are due to undigested carbohydrates, and tend to diminish over time as the intestinal tract adapts.
Thiazolidinediones –This class of drugs act to increase the sensitivity of tissues to insulin by stimulating a receptor in the body called PPAR gamma receptor. This receptor affects many actions involved in glucose production, transport and use. The first drug in this class, troglitazone (Rezulin) was introduced in 1997, but had to be withdrawn in March 2000 due to cases of acute liver failure. Two other drugs in the same chemical class, rosiglitazone (Avandia) and pioglitazone (Actos) are currently on the market, but monitoring of the liver status is essential.
Summary – Great strides have been made in understanding the causes of diabetes, and to develop increasingly effective means of treating the disease that will minimize the occurrence of long-term detrimental effects. The best way to prevent non-insulin dependent diabetes is to adopt a lifestyle recommended for all Americans. This includes moderate exercise and adoption of federal dietary guidelines to avoid excessive weight gain. One of the greatest challenges confronting researchers today is to develop methods to help prevent the occurrences of insulin dependent diabetes. There is promise on the horizon to develop a vaccine or drug that will prevent the autoimmune attack on the pancreatic beta cells that produce insulin.
Further Reading
1.Atkinson, M. and Maclaren, N. “What Causes Diabetes?” Scientific American, 263 (1): 62-71, July 1990
2. Bell, D. “Current Status of Diabetes Treatment.” South Med J 95 (1): 24-29, 2002
3. “Diabetes Demands a Triad of Treatments.” FDA Consumer, May-June, 1888 (revised Oct. 1999)
4. “Management of Type 2 Diabetes: Finding a Sensible Pathway through the Maze of Available Agents.” Drug Ther Perspect 17 (14): 4-8, 2001
5. Polonsky, K., Sturis, J. and Bell, G. “Non-Insulin Dependent Diabetes Mellitus- a Genetically Programmed Failure of the Beta Cell to Compensate for Insulin Resistance.” New England Journal of Medicine, 334 (12): 777-782, 1996
Resource Items
American Diabetes Association
Attn: Customer Service
1701 N. Beauregard St.
Alexandria, VA 22311
1-800-342-2383
National Diabetes Information Clearinghouse
1 Information Way
Bethesda, MD 20892-3560
(301) 654-3327