Type 1 Diabetes
Is Type 1 Diabetes?
The two major forms of diabetes are type 1 (previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes) and type 2 (previously called noninsulin-dependent diabetes mellitus (NIDDM) or maturity-onset diabetes). They share a central feature: elevated blood sugar levels due to absolute or relative insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. After meals, food is digested in the stomach and intestines; carbohydrates are broken down into sugar molecules, of which glucose is one, and proteins are broken down into amino acids. Glucose and amino acids are absorbed directly into the bloodstream, and blood glucose levels rise. Normally, the rise in blood glucose levels signals important cells in the pancreas -- called beta-cells -- to secrete insulin, which pours into the bloodstream. Insulin, in turn, enables glucose and amino acids to enter cells in the body -- importantly, those in the muscles -- where, along with other hormones, it directs whether these nutrients will be burned for energy or stored for future use. As blood sugar falls to pre-meal levels, the pancreas reduces the production of insulin, and the body uses its stored energy until the next meal provides additional nutrients.
In type 1 diabetes, the beta-cells in the pancreas that produce insulin are gradually destroyed; eventually insulin deficiency is absolute. Without insulin to move glucose into cells, blood sugar levels become excessively high, a condition known as hyperglycemia. Because the body cannot utilize the sugar, it spills over into the urine and is lost. Weakness, weight loss, and excessive hunger and thirst are among the consequences of this "starvation in the midst of plenty". Patients become dependent on administered insulin for survival. (Sometimes type 1 patients can experience remission and go off insulin, but these "honeymoon" periods are virtually never permanent; they usually occur shortly after diagnosis and are short-lived.)
Type 2 diabetes is by far the more common diabetes. Most type 2 diabetics appear to produce variable -- even normal -- amounts of insulin, but have abnormalities in liver and muscle cells that resist its action. Insulin attaches to the receptors of cells, but glucose does not get insidea condition known as insulin resistance. Because many type 2 diabetics seem to be incapable of secreting enough insulin to overcome this resistance, however, it is likely that in such cases there is an additional defect in insulin secretion by the beta-cells. While many patients can control type 2 diabetes with diet or with medications that stimulate the pancreas to release insulin, commonly the condition worsens and may require insulin administration. Maturity-onset diabetes in youth (MODY) is a rare genetic form of type 2 diabetes that usually develops in thin teenagers. About 0.5% of pregnant women develop a form of type 2 diabetes called gestational diabetes in their third trimester.
Secondary to Other Conditions
Conditions that damage or destroy the pancreas, such as pancreatitis, pancreatic surgery, or certain industrial chemicals can cause diabetes. Certain drugs can also cause temporary diabetes, including corticosteroids, beta blockers, and phenytoin. Rare genetic disorders (Klinefelter's syndrome, Huntington's chorea, Wolfram's syndrome, leprechaunism, Rabson-Mendenhall syndrome, lipoatrophic diabetes, and others) and hormonal disorders (Acromegaly, Cushing's syndrome, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma) also increase the risk for diabetes.
Causes Type 1 Diabetes?
Type 1 diabetes is usually preceded by an asymptomatic stage known as insulitis, in which the immune system's T cells, a type of white blood cell, begin to infiltrate and destroy the beta-cells of the pancreas. Ordinarily these so-called killer T cells fight infection, but in the case of diabetes, a mechanism known as an autoimmune response turns them against the body's own tissues. It is unknown what triggers this phenomenon, but evidence suggests both a genetic predisposition and environmental factors, perhaps, in some instances, a viral infection. Progression from insulitis to full blown diabetes can take seven years or longer. (More than one half of those with insulitis, however, do not develop diabetes. Of considerable interest is a study reporting that high-risk people with high levels of an immune factor called interleukin 4 (IL-4) may be protected from developing the disease.) By the time a person is aware that something is wrong and goes to the doctor with symptoms of type 1 diabetes, about 80% to 90% of the beta-cells have been destroyed.
Researchers have found at least 18 genetic locations that are related to type 1 diabetes. They appear to involve abnormal interactions among normal genes, mostly those known as class I and II major histocompatibility genes, which affect the immune response. The odds of inheriting the disease, however, are only 10% if a first degree relative has diabetes, and even in identical twins, one twin has only a 33% chance of having diabetes if the other has it. Children are more likely to inherit the disease from a father with type 1 diabetes than from a mother with the disorder. Genetic factors, however, cannot fully explain the development of diabetes. Over the past 30 years, a major increase in the incidence of type 1 diabetes has been reported in certain European countries, and the incidence has nearly tripled in the Northeastern US. If genetic factors were the only cause of type 1 diabetes, such an increase in cases would take at least 400 years.
Some researchers believe one or more viral infections may trigger the disease in genetically susceptible individuals. Researchers suggest that an infection introduces a viral protein resembling a beta-cell protein. The T cells and antibodies to the foreign protein are tricked by this resemblance into attacking the beta protein as well as the virus. Viruses under scrutiny include those that attack the intestinal tract (called enteric viruses), particularly coxsackieviruses. One study has indicated that early respiratory infection -- in a child's first year and not later -- may be protective against diabetes, perhaps by priming the immune response so that it is better able to respond later on to other organisms.
Under investigation is a link between type 1 diabetes and exposure to cow's milk early in infancy. One study found 1.5% of infants who are fed cow's milk go on to develop type 1 diabetes, and another found that children fed cow's milk in the first eight days of life had twice the risk as those on breast milk. A protein called bovine serum albumin (BSA), which might develop in children who are fed cow's milk in early infancy, resembles a protein in beta-cells. Some researchers believe that the antibodies formed to respond to BSA may later on attack the child's beta-cells. It should be noted, however, that children with diabetes have no higher levels of BSA antibodies than non-diabetic children; more research is needed to refute or confirm the association.
Gets Type 1 Diabetes?
Up to 800,000 people in the U.S. are estimated to have type 1 diabetes, with about 30,000 new cases diagnosed each year. It is much less common than type 2, however, consisting of only 7% to 10% of all cases of diabetes. Type 1 can occur at any age but usually appears between infancy and the late 30s, most typically in childhood or adolescence. Boys and girls are equally vulnerable. Although still an uncommon disease, the incidence has been rising over the past few decades in certain regions of the U.S. and some European countries, particularly in Finland and England. While type 1 diabetes appears to be most common in people of northern European, it is rare among Asians and African Americans. The incidence of type 1 is increased among people with certain autoimmune diseases, including Grave's disease, Hashimoto's thyroiditis, Addison's disease, and pernicious anemia.
Are the Symptoms of Type 1 Diabetes?
The process that destroys the insulin-producing beta-cells can be a long and insidious one. At the point when insulin production bottoms out, however, type 1 diabetes usually appears suddenly and progresses quickly. Warning signs of type 1 diabetes include: frequent urination; in children, a recurrence of bed-wetting after toilet training has been completed; unusual thirst, especially for sweet, cold drinks; extreme hunger; sudden, sometimes dramatic, weight loss; weakness; extreme fatigue; blurred vision or other changes in eye sight; and irritability. Children with type 1 diabetes also may be restless, apathetic, and have trouble functioning at school. In acute cases of type 1 diabetes, nausea and vomiting may occur. In severe cases, diabetic coma may be the first sign of type 1 diabetes (see Emergency Conditions under How Serious is Diabetes?, below).
Serious Is Type 1 Diabetes?
Type 1 diabetes reduces the normal life span by an average of five years. This risk is the same regardless of -- ethnic background, although the disease is slightly more serious in women.
Ketoacidosis. Diabetic ketoacidosis is a life-threatening complication of type 1 diabetes. It is almost always caused by noncompliance with insulin treatments; infections or other stresses can also increase the risk. Not only is there usually an excessive amount of glucose present in the bloodstream, but fat breakdown accelerates the production of fatty acids; these are converted into chemicals called ketone bodies, which at high levels are toxic. Symptoms of ketoacidosis include nausea and vomiting and, in children, abdominal pain. Breathing may be abnormally deep and rapid with frequent sighing. The heartbeat may be rapid. If the condition persists, coma and, eventually, death may occur, although over the past 20 years, death from ketoacidosis has decreased to about 2% of all cases. Other serious complications from ketoacidosis include cerebral swelling in children, aspiration pneumonia, and adult respiratory distress syndrome. The annual incidence of diabetic ketoacidosis ranges from 30 to 80 episodes per 1,000 persons with diabetes. The risk is much higher in adolescents -- both girls and boys -- because they are less apt to comply with insulin therapy. Life-saving treatment includes insulin administration to correct glucose and ketone metabolism and rapid fluid and electrolyte replacement.
Hypoglycemia. Intensive insulin or treatments that produce insulin, such as sulfonylureas, increase the risk of hypoglycemia (or insulin shock), which occurs if blood glucose levels fall below normal. Hypoglycemia may also be caused by insufficient intake of food, exercise, or alcohol intake. Usually the condition is manageable, but occasionally, it can be severe or even life threatening, particularly if the patient fails to recognize the symptoms. Mild symptoms usually occur at moderately low and easily correctable levels of blood glucose; they include sweating, trembling, hunger, and rapid heartbeat. Severely low blood glucose levels can precipitate neurologic symptoms -- confusion, weakness, disorientation, combativeness, and in rare and worst cases, coma, seizure, and death. Patients who experience repeated episodes of hypoglycemia may become insensitive to symptoms; even a single recent episode of hypoglycemia may make it more difficult to detect the next episode. By rigorously avoiding low blood glucose, such patients can regain the ability to sense the symptoms. Most experts recommend that patients monitor blood levels as often as possiblefour times or more per day. This is particularly important for patients who have a history of experiencing no symptoms of hypoglycemia before mental changes occur. Experts have been concerned that the increased incidence of hypoglycemia accompanying strict blood glucose control could cause mental deterioration over time, but a six-year study has found no evidence of this in adolescents and adults. (The effect on young children, however, is not known).
Diabetic patients should always carry hard candy, juice, or sugar packets. Family and friends should be aware of the symptoms. If the patient is helpless, they should administer three to five pieces of hard candy, two to three packets of sugar, or half a cup (four ounces) of fruit juice. If there is inadequate response within 15 minutes, additional oral sugar should be provided or the patient should receive emergency medical treatment including the intravenous administration of glucose. Family members and friends can learn to inject glucagon, a hormone, which, unlike insulin, raises blood glucose.
Hypoglycemia is a common problem during sleep, particularly for children -- even those on non-intensive insulin therapy. (The risk for hypoglycemia is high in any case in children.) Bedtime snacks may be helpful. One study found that taking the drug alanine or terbutaline may be more effective than snacks. It should be noted that high amounts of terbutaline (which is also used for asthma) increases the risk for ketoacidosis.
Complications of Diabetes
The major complications in diabetes are due to vascular (blood vessel) abnormalities and nerve damage (neuropathy). Injuries in large blood vessels endanger the heart, particularly in people with existing heart disease or high blood pressure, and can cause leg problems. Small blood vessel (microvascular) changes can harm the eyes and kidneys.
Cardiovascular Complications. Heart attacks account for 60% and strokes for 25% of deaths in all diabetics. Both type 1 and 2 diabetes accelerate the progression of atherosclerosis, a process whereby layers of yellowish plaque made up of cholesterol, fats, and other particles build up in the walls of arteries. As the arteries narrow, blood flow slows and the blood vessels may become blocked. This can lead to coronary artery disease, heart attack, or stroke. In type 1 diabetes, high blood pressure usually develops if the kidneys become damaged. High blood pressure is another major cause of heart attack, stroke, and heart failure.
Neuropathy, Vascular Injury, and Amputations. In 60% to 70% of patients, diabetes can lead to neuropathy, which is decreased or distorted function in the nerves, particularly affecting those responsible for sensation. Symptoms include numbness, tingling, weakness, and burning sensations, usually starting in the fingers and toes and moving up to the arms and legs. If the nerves are damaged as well, the person may be unaware that even a blister or minor wound has become infected. The problem is compounded in diabetes because of circulatory problems resulting from blood vessel injury, which may be severe enough to cause tissue damage in the legs and feet. Even minor infections can develop into deep tissue injury. Extensive surgery may be required, and, in extreme cases, amputation of the foot or leg may be necessary. Diabetes is responsible for more than half of all the lower limb amputations performed in the US each year. Early and aggressive treatment of people who are at particular risk for foot and leg problems can prevent 50% of amputations.
If diabetes affects the nerves in the autonomic nervous system, abnormalities of blood pressure control, bowel and bladder function, and male sexual function can occur. In some cases, neuropathy may block anginathe warning chest pain for heart disease and heart attack. Diabetic patients should be aware of other warning signs of a heart attack, including sudden fatigue, sweating, shortness of breath, nausea, and vomiting.
Eye Complications. Diabetes accounts for 12,000 to 24,000 new cases of blindness annually and is the leading cause of new cases of blindness in adults ages 20 to 74. Given long duration of the disease and low control of insulin administration, nearly all type 1 diabetics will develop retinopathy -- abnormalities of the blood vessels in the retina -- at some point in their lives, although only a minority of cases cause severe vision loss or blindness. By the seventh year retinal damage has occurred in 50% of type 1 patients, and after 14 years, more than 90% develop retinopathic changes. In nonproliferative or background retinopathy, the early and more common type of this disorder, abnormally weakened blood vessels in the retina rupture and leak, and waxy areas may form. If these processes affect the central portion of the retina, swelling may occur causing reduced or blurred vision. If the weak blood vessels become blocked and blood flow is cut off, soft, "woolly" areas may develop in the retina's nerve layer. These areas may signal the development of proliferative retinopathy; in this more severe condition, new, abnormal blood vessels form and grow on the surface of the retina. They may spread into the cavity of the eye or bleed into the back of the eye; major hemorrhage or retinal detachment can result, possibly causing severe visual loss or blindness. Although the sensation of seeing flashing lights may indicate retinal detachment, often there are no symptoms of progressing retinopathy. People with diabetes are also at higher risk for developing cataracts and certain types of glaucoma.
Kidney Damage (Nephropathy). Kidney disease develops in about a third of type 1 diabetics and is the primary cause of disability and death in these patients. The risk for this complication increases with coronary artery disease, hypertension, and problems in the urinary tract. Symptoms include swelling in the feet and ankles, fatigue, and pale skin color.
Other Complications. People with diabetes are at higher risk for influenza and its complications, including pneumonia, possibly because the disorder neutralizes the effects of protective proteins on the surface of the lungs. Scaly and hardened skin may develop after a patient has had diabetes for many years. Such skin changes may be indicators of other complications, including retinopathy. There has been some concern that type 1 diabetics are at risk for bone-density loss, although a recent two-year study found little basis for alarm. Longer studies are needed. Type 1 diabetes also appears to increase the risk for celiac disease, an allergy to gluten, found in corn and wheat. Both women and men with diabetes appear to have a higher risk for colon and rectal cancers.
Specific Complications in Women. Both temporary diabetes that occurs during pregnancy (gestational diabetes) and pregnancy in a patient with existing diabetes can increase the risk for birth defects. Because glucose crosses the placenta, hyperglycemia can be passed on to the fetus. In response to abnormally high blood glucose levels, the fetus secretes large amounts of insulin. This combination of high fetal blood levels of both insulin and glucose leads to excessive fetal growth. It may also delay maturation of the lungs or cause the death of the fetus. Diabetes also presents risks to the pregnant woman, particularly preeclampsia, a potentially dangerous condition involving very high blood pressure. Studies indicate that hyperglycemia may effect the developing fetus as soon as it is conceived. Diabetic women who want to become pregnant should be diligent about controlling blood glucose levels before and during pregnancy.
Diabetes appears to affect female hormones. It seems to blunt the beneficial effects of estrogen, increasing the risk for heart disease. Women with type 1 diabetes often have lumps in the breast that are benign but which make mammograms difficult to interpret. It is not clear whether these lumps are risk factors for breast cancer. One study indicated that women with diabetes have a higher risk for endometrial cancer and possibly for breast cancer. They also have a higher risk for early menopause, which, in one study, occurred at an average age of about 41 years.
Specific Complications for Adolescents. Blood sugar control is a major problem in adolescents with type 1 diabetes, who are at high risk for permanent damage in small vessels, such as those in the eyes. Up to one third of young women with type 1 diabetes have eating disorders resulting in under use of insulin to lose weight. Anorexia and bulimia pose significant health dangers, particularly in people with diabetes. One study found that young people with diabetes have a higher than average rate of suicidal fantasies. Although the actual rate of suicide was no higher than that of their non-diabetic peers, such thoughts are strongly associated with self-destructive behavior, including low treatment compliance. Adolescents with diabetes are at higher risk than adults for ketoacidosis resulting from non-compliance.
Is Type 1 Diabetes Diagnosed?
People at Risk for Diabetes
Researchers are looking for reliable and inexpensive methods for identifying high-risk people who are most likely to develop diabetes. One method is by detecting specific autoantibodies that attack the body's own proteins and trigger the diabetic process. Two such targets are a beta-cell protein known as GAD (glutamic acid decarboxylase) and tyrosine phosphatase IA2. Testing for antibodies to each of the proteins is not accurate, but testing them in combination may prove to be highly sensitive for identifying those at highest risk for the disease and who would require close monitoring. C-peptide is a small protein that is a natural byproduct of insulin synthesis and is deficient in type 1 diabetes. Repeated measurements of C-peptide are useful in assessing the decline in betacell functions and may target people at risk for diabetes who may benefit from experimental preventive therapies.
Fasting Plasma Glucose. The fasting plasma glucose (FPG) test has become the standard diagnostic test. It is a simple blood test taken after eight hours of fasting. FPG level are considered normal up to 110 mg/dl. Diabetes is diagnosed when FPG levels are 126 mg/dl or higher on two different days. Levels between 110 and 126 are referred to as impaired fasting glucose, which is considered to be a risk factor for developing diabetes and its complications. The test is not always reliable; if a person has normal levels but has symptoms of diabetes and a family history or other risk factors, then diabetes should not be ruled out and other tests should be performed.
Glucose Tolerance Test. A glucose tolerance test is more elaborate; it first employs an FPG test; a blood test is then taken two hours later after drinking a special glucose solution. Normally, blood sugar increases modestly after drinking the glucose beverage and decreases after two hours; in the diabetic, the initial increase is excessive and the level remains high.
Test for Glycolated Hemoglobin. Another diagnostic test examines blood levels of hemoglobin A1c (HbA1c), or glycolated hemoglobin. Hemoglobin, a protein molecule found in red blood cells, becomes modified by having glucose bound to it. The degree of modification depends on the average level of blood sugar that the protein is exposed to over its life span. Although the HbA1c test detects less than half of those with diabetes, the patients identified are those most severely affected and who require medical intervention. The test is also used to monitor the effectiveness of diabetic treatments.
Tests for Complications
The earliest manifestation of kidney damage is microalbuminuria, in which tiny amounts (30 to 300 mg per day) of protein called albumin are found in the urine. Microalbuminuria is also marker for other complications involving blood vessel abnormalities. (Contrary to previous reports, microalbuminuria does not appear to be an indicator of heart disease.) A blood test that indicates elevated levels of a substance called metalloproteinase-9 may be an even earlier predictor for kidney damage, allowing early intervention to prevent complications. All patients should be tested for hypertension. Tests for cholesterol and lipid levels, an electrocardiogram, and possibly thyroid function tests should be performed.
Are the General Guidelines for Treating Type 1 Diabetes?
Insulin is essential for survival and is the mainstay treatment for type 1 diabetics. A diet plan that compensates for insulin administration and supplies healthy foods is extremely important. Major studies have now provided substantial evidence that intensive treatment with insulin and tight control of blood glucose levels significantly delay the major complications specific to diabetes, including nephropathy and neuropathy. Intensive insulin treatment in early diabetes also helps preserve any residual insulin secretion for at least two years. The primary complication for intensive insulin therapy is a much higher risk for hypoglycemia. Many patients also experience significant weight gain with adverse effects on blood pressure and cholesterol levels. It is important then, to manage cardiovascular risk factors that might develop as a result of intensive treatment. Intensive treatment also appears to cause early signs of retinopathy; after four years, however, in one study, there was no difference in retinopathies between patients who had intensive treatment versus those on standard care. Pancreas transplantation eventually may be recommended for patients who cannot control glucose levels without frequent episodes of severe hypoglycemia.
Are Lifestyle Measures for Type 1 Diabetes?
For most people with diabetes, diet control is the key to managing this complicated disease. It is also extremely difficult. The current state of the diabetic diet is in flux, and at this time, there is no single diet that meets all the needs of everyone with diabetes. People with type 1 diabetes should coordinate insulin administration with calorie intake. In general, they should eat three meals each day at regular intervals; snacks are often required. They should try to take an insulin injection 30 minutes before they eat, although this timing could vary, depending on the form. One simple recommendation is simply to avoid cow's milk and products made from it.
All people with diabetes should aim for healthy lipid (cholesterol and triglyceride) levels and control of blood pressure. Adequate calories must be maintained for normal growth in children, for increased needs during pregnancy, and after illness. And the general rules for healthy eating apply to everyone: limit fats (particularly saturated fats and trans-fatty acids), protein, and cholesterol, and consume plenty of fiber and fresh vegetables. Reducing salt is also important. Patients should meet with a professional dietitian to plan an individualized diet that takes into consideration all health needs.
Weight gain is a potential side effect of intense diabetic control with insulin. One study reported that 37% of diabetic women omitted or underused insulin to control weight. Eating disorders have become a serious problem within the general population and are especially dangerous in diabetics.
Aerobic exercise is proving to have significant and particular benefits for people with type 1 diabetes; it increases sensitivity to insulin, lowers blood pressure, improves cholesterol levels, and decreases body fat. Because glucose levels swing dramatically during workouts, people with diabetes should monitor their levels carefully before, during, and after workouts, and should probably not exercise if levels are above 300 mg/dl. To avoid hypoglycemia, diabetics should inject insulin in sites away from the muscles they use the most during exercise. They should also avoid drugs, including beta-blockers and alcohol, that increase the risk of hypoglycemia. Finally, insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates, especially in the form of pre-exercise snacks (skim milk is particularly helpful). They should also drink plenty of fluids. Because diabetics may have silent heart disease, they should always check with their physicians before undertaking vigorous exercise. Exercise, particularly resistance or high impact exercises, can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet.
Preventive foot care could reduce the risk of amputation by 44% to 85%. Patients inspect their feet daily and watch for changes in color or texture, odor, and firm or hardened areas, which may indicate infection and potential ulcers. When washing the feet, the water should be warm (not hot) and the feet and areas between the toes should be thoroughly dried afterward. Moisturizers should be applied, but not between the toes. Corns and calluses should be gently pumiced and toenails trimmed short and the edges filed to avoid cutting adjacent toes. Patient should not use medicated pads or try to shave the corns or calluses themselves. They should avoid high heels, sandals, thongs, and going barefoot. Shoes should be changed often during the day. Tight stockings or any clothing that constricts the legs and feet should be avoided. A specialist in foot care should be consulted for any problems.
Annual flu shots are strongly recommended. People with diabetes should also discuss a single vaccination against pneumococci, the most common cause of pneumonia.
A daily low dose aspirin is advised for people with diabetes at risk for heart disease. One study found that 100 mg/day helped reduce blood-glucose related complications.
Is Insulin and How Is It Used to Treat Diabetes?
for Intensive Insulin Treatment
The goal of intensive therapy is to keep blood glucose levels as close to normal as possible. In one major study even when levels were 40% higher than non-diabetic levels, benefits were still observed. Intensive treatment usually involves three or more daily insulin injections or use of an insulin pump. In addition, during the day the patient should take four or more blood glucose tests. The patient must also maintain a good diet plan and should visit the health care team of doctors, nurses, and dietitians once a month. (Standard insulin therapy is usually one or two insulin injections, one daily blood sugar test, and visits to the health care team every three months.) The regimen is complicated. To save time, some people administer injections directly through their clothing; although not recommended, one study found that it did not increase the risk for infection. Because of the higher risk for hypoglycemia, experts recommend that intensive treatment be used very cautiously in children under 13 and not at all in very young children. One study has indicated that thin children are at higher risk for hypoglycemia, because the injection goes into muscle tissue. Pinching the skin so that only fat tissue is gathered and not muscle or using shorter needles may help.
Insulin cannot be taken orally because the body's digestive juices destroy it. Injections of insulin under the skin ensure that it is absorbed slowly by the body for a long-lasting effect. The timing and frequency of insulin injections depend upon a number of factors, including the type of insulin, amount and type of food eaten, and the person's level of physical activity. For example, ingestion of food makes the blood glucose level rise, whereas exercise and alcohol make blood glucose levels fall. Insulin is available in several brands, including Humulin, Novalin, and Iletin. Longer-acting insulins, referred to as NPH or L, can last up to 24 hours. Regular insulin (R) takes effect more rapidly and its actions last four to 12 hours. Insulin lispro (Humalog) lowers blood sugar even more quickly and, because of its rapid effectiveness, is particularly beneficial when taken right before eating. Its short action also reduces the risk for hypoglycemic events afterward. Lispro may also be used shortly after a meal starts if a patient forgets to take insulin beforehand. (Lispro should not be used regularly in this manner, however.) Taking it right after a meal may prove to be useful in toddlers, who frequently refuse to eat meals on schedule. Lispro has no effect on glycolated hemoglobin levels, however. Patients who may benefit from lispro are those with low glycolated hemoglobin levels but who are at high risk for hypoglycemia and those with recent-onset diabetes who still have some beta-function and can maintain some insulin levels between meals. There is some indication that it may cause birth defects if pregnant women take it.
Alternatives to Injections. Insulin pumps have become more reliable and easy to use, and studies are finding that those who use them have fewer hypoglycemic episodes than intensive insulin therapy and their quality of life is higher. Some pumps are worn externally, and the wearer can program them to deliver insulin through a catheter in the skin or the abdomen. The box-like programming device is lightweight, about the size of a pack of cards, and has a digital display. Programmable pumps are proving to improve qualify of life, control blood glucose, and reduce hypoglycemia compared to injections. In type 2 diabetes, they are also reducing the need for antihypertensive medications. They are more expensive than insulin shots, however, and have complications, such as blockage in the device. An inhaled aerosol spray is proving to be as effective as injections. A large study is underway. Other promising avenues of investigation are use of ultrasound pulses to deliver insulin through skin patches, and implanted pellets. Some studies are testing oral or inhaled insulin to prevent type 1 diabetes in people with close relatives with the disease and who show evidence of beta-cell deterioration.
Tests for Blood Glucose Levels. Both hypoglycemia and hyperglycemia are of concern for patients who are receiving insulin. It is important, therefore, to monitor blood glucose levels carefully. In general, patients with type 1 diabetes need to take readings four or more times a day. Patients should aim for premeal glucose levels of between 80 and 120 and bedtime levels of between 100 and 140. Different goals may be required for specific individuals, including pregnant women, very old and very young people and those with accompanying serious medical conditions. Usually, a drop of blood obtained by pricking the finger is applied to a chemically treated strip. A laser finger-prick device is now available that may be particularly beneficial for children. The glucose level is read on a standard meter or a small, portable digital display device. Home monitors are about 10% to 15% less accurate than laboratory monitors and many do not meet the standards of the American Diabetes Association. One, called SureStep, has recently been recalled because it did not specifically warn patients of dangerously high glucose levels. Many experts believe, however, that most are accurate enough to indicate when blood sugar is too low. Some simple procedures may improve accuracy: testing the meter once a month; recalibrating it whenever a new packet of strips is used; using fresh strips; keeping the meter clean; and periodically comparing the meter results with the results from a laboratory. Monitoring is expensive, costing 50 cents for each strip. Researchers are testing various noninvasive monitors, such as skin patches and infrared devices. A monitoring device implanted under the skin in the abdomen is also being tested.
Tests for Glycolated Hemoglobin. Hemoglobin A1c (Hb A1c), or glycolated hemoglobin, is measured periodically to determine the average blood-sugar level over the life span of the red blood cell, which is about 8 to 10 weeks. Hb A1c should be below 7%. High levels are markers for kidney trouble. These tests are taken about twice a year in patients who are maintaining blood sugar levels and more frequently in those who are having difficulties or who have changed medications.
Urine Tests. Urine tests are useful for detecting the presence of ketones, which should always be performed during illness or stressful situations, when diabetes is likely to go out of control. The patient should also undergo yearly urine tests for microalbuminuria (small amounts of protein in the urine), a risk factor for future kidney disease.
Eye Examinations. For those on intensive insulin therapy, experts recommend an eye examination when starting treatments and every three months thereafter up to a year.
Are Other Experimental Therapies for Preventing or Treating Type 1 Diabetes?
Although insulin is the mainstay of type 1 diabetes treatment, research is on-going to develop other approaches that might, in time, even be curative. The basis for nearly all experimental measures for prevention and treatment of type 1 diabetes are stabilization of beta-cells. Preventive measures are sometimes defined as primary and secondary. Primary prevention attempts to preserve all beta-cells before the disease process starts while secondary prevention hopes to deter further beta-cell destruction once it has started and before symptoms arise. Treatment techniques are those aimed at stabilizing any remaining beta-cells at or after diagnosis.
and Vitamin E
Nicotinamide, a derivative of vitamin B3, may protect beta-cells from the damaging inflammatory processes triggered by the immune system. Some trials are studying the addition of nicotinamide to an insulin regimen in patients who have just been diagnosed with diabetes. Several large trials are underway to determine if high doses can protect children at risk for diabetes. Vitamin E may also offer some protection, and some experts recommend trials of both vitamins.
Research is on-going to develop treatments that use the body's own immune system to impede or prevent beta-cell destruction. Drugs that suppress the immune system, azathioprine and cyclosporine, which are used for other autoimmune diseases, have not proven to be beneficial. One approach has patients eating forms of insulin or GAD, the beta-cell protein that might be involved in triggering the immune system's attack. The premise behind this treatment is that the immune system is more tolerant of proteins that are eaten than of those that enter the blood stream directly. Theoretically, once the immune system gets used to the oral form, it will cease to attack the resident GAD or insulin proteins in the body. Investigators are also testing antibodies that specifically block certain molecules that are known to attack beta-cells in mice with inflamed pancreases.
Two drugs, diazoxide and octreotide, are being studied for their ability to control the release of insulin in the very early stages of diabetes. This inhibition of insulin secretion may allow beta-cells to "rest" and preserve residual insulin.
Are Transplantation Procedures?
Whole pancreas transplants have helped to prevent further kidney damage, and long-term studies are finding that they may even reverse existing damage after many years. Diabetic neuropathy improves, but not retinopathy. Double transplants of pancreases and kidneys are also proving to have a good long-term success rate for selected type 1 patents. One ten-year study reported that survival rate at 10 years was 76.3%, and two thirds of the patients had both pancreas and kidney function. Drugs are needed after transplantation procedures to suppress the immune system so that it doesn't reject these foreign organs. Side effects of these drugs can be severe.
Transplants of beta-cell islets have also been performed, but immunosuppressive drugs are also required for these procedures. In some patients, particularly those who receive transplants from genetically matched donors, the autoimmune process continues to kill beta-cells. Procedures using beta-cells taken from the pancreas of animals and encapsulated in protective spheres are allowing secretion of insulin while protecting against attack by the immune system. Human clinical trials are pending.
Are Complications of Type 1 Diabetes Prevented and Treated?
Patients who control high blood pressure, keep regular doctor visits, and rigorously self-manage their insulin therapy can have a complication rate that is one-third lower than patients who do not take such actions. With intensive treatment weight gain is common, however, putting patients at risk for high blood pressure and unhealthy cholesterol levels. Everyone, and especially people with diabetes, should maintain a healthy lifestyle.
and Prevention of Nephropathy
Tight Control of Blood Glucose. A number of studies have shown that tight blood glucose control using intensive insulin therapy delays progression of kidney disease. High hemoglobin A1 (glycolated hemoglobin) levels may relate directly to a risk for kidney dysfunction. One study indicated, in fact, that patients could reduce the risk for kidney disease by maintaining glycolated hemoglobin levels at 8% or below rather than trying to keep strict control of glucose levels. (Such a strategy might also help prevent retinopathy.)
Controlling High Blood Pressure. Control of existing high blood pressure is extremely important not only for preventing progression to kidney failure but also to prevent heart disease, stroke, and heart failure. For diabetics, the best drugs are beta blockers or angiotensin-converting enzyme (ACE) inhibitors. Beta blockers are less expensive and one study found that they were as effective as ACE inhibitors in reducing complications of diabetes through control of blood pressure. ACE inhibitors, however, have been shown to delay the onset and progression of kidney disease by 30% to 60%, even in those without hypertension. A recent study indicates that this beneficial effect may occur mainly in people who have a specific genetic type. ACE inhibitors may even help prevent or limit progression of food ulcers and retinopathy. There is some evidence that they increase the risk for hypoglycemia.
The tricyclic antidepressant amitriptyline (Elavil) and topical capsaicin (the active ingredient in hot peppers) are commonly used for neuropathy pain. Other antidepressants are also showing promise for relieving pain and numbness, including sertraline (Zoloft) -- a serotonin reuptake inhibitors (SSRIs) -- and nefazodone (Serzone), a newer antidepressant. Both have fewer side effects than the tricyclic. The anti-seizure drug gabapentin (Neurontin) may be as effective as amitryptyline, although it is more expensive. Tramadol (Ultram), a pain killer that is similar to opioids, achieved moderate pain reduction in one study and may have fewer side effects than anti-seizure drugs or tricyclics, although it carries a risk for addiction and nausea, headache, and constipation are common. Investigators are also testing nerve-growth factor, which promotes nerve survival. In one study, patients taking it experienced both greater sensation and dramatically reduced levels of pain and discomfort. The only side effect was discomfort at the injection site. Vitamin E supplements may be helpful. If foot pain, numbness, or tingling is worse at night, diphenhydramine (Benadryl) may help. Delayed stomach emptying caused by neuropathy may be helped by erythromycin or metoclopramide (Reglan).
and Prevention of Retinopathy
A number of drugs are being studied for the prevention of retinopathy. Two that show some promise are epalrestat and tolrestat, which are drugs known as aldose reductase inhibitors. Studies are investigating aspirin, a combination of aspirin and dipyridamole (Persantine), and ticlopidine (Ticlid), but although the drugs appear to reduce the number of ruptured blood vessels, they do not seem to prevent retinopathy from developing. Once damage to the eye develops, laser photocoagulation and other forms of eye surgery may be needed. Because intense glucose control can cause early worsening of retinopathy, some experts recommend delaying intensive treatment in people at high-risk for retinopathy until the eye problems are surgically treated.
of Foot Ulcers
Hospitalization and intravenous antibiotics for up to 28 days may be needed for severe foot ulcers in diabetic patients. In one study, intravenous therapy using ofloxacin or penicillin for only seven days followed by an oral antibiotic was adequate treatment. A number of treatments (Dermagraft, Apligraf, Regranex) are now available that stimulate new cell growth and help heal skin ulcers or use cultures of human skin cells, although their benefits are still unproven. Granulocyte-colony stimulating factor, or G-CSF (filgrastim, Neupogen, Amgen) is showing promise as an effective alternative to antibiotics. One study showed that G-CSF accelerated healing and significantly reduced the need for surgery. One study indicated that administering hyperbaric oxygen (given at high pressure) promoted healing and helped prevent amputation. There was no follow-up however, and more research is needed.
ACE inhibitor use is associated with hospitalization for severe hypoglycemia in patients with diabetes. Diabetes Care, September 1997
Aspirin for diabetics. NewsBites, HealthNews, 11/18/1997
Beta-cell rest: a strategy for the prevention of autoimmune diabetes. Autoimmunity 1997;26(2):117-22
Chronic illness: the exercise prescription. Consumer Reports on Health. January 1997
Dangerous false readings prompt recall of blood glucose meters. FDA Consumer November-December 1998
The Deutsche Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes. Diabetes 1998 Jun;47(6):980-4
The Diabetes Control and Complications Trial Research Group. Effects of intensive diabetes therapy on neuropsychological function in adults in the DCCT. Annals of Internal Medicine, 2/15/96
Diabetes: How much testing? Consumer Reports on Health, March 1998
Drug therapy: insulin lispro. The New England Journal of Medicine, 7/17/97
Diabetes therapy: Watch the eyes. HealthNews, 9/10/98
Eating disorders and diabetic complications. The New England Journal of Medicine, 6/26/97
Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure. JAMA, 7/89/98, Vol 290, p. 140
Effectiveness of postprandial Humalog in toddlers with diabetes. Pediatrics. December 1997, Vol 100, p. 968
Help for healing skin ulcers. FDA Consumer, September-October 1998.
Implantable insulin pump vs multiple-dose insulin for non-insulin-dependent diabetes mellitus. A randomized clinical trial. Journal of the American Medical Association October 23/30 1997
Induction of beta-cell rest in type 1 diabetes. Studies on the effects of octreotide and diazoxide.
Insulin options. HealthNews, 6/1/98
New skin for old: Developments in biological skin substitutes. Archives of Dermatology, March 1998, vol 134, p.
Pancreas transplantation and diabetic complications. The New England Journal of Medicine, 7/9/98, Vol. 339, p. 115
Board of Editors
Simon, M.D., Editor-in-Chief
Massachusetts Institute of Technology; Physician, Massachusetts General Hospital
J. Etkin, M.D., Gynecology
Harvard Medical School; Physician, Massachusetts General Hospital
E. Godine, M.D., Ph.D., Metabolism
Harvard Medical School; Associate Physician, Massachusetts General Hospital
Heller, M.D., Pediatrics
Harvard Medical School; Associate Pediatrician, Massachusetts General Hospital; Active Staff, Children's Hospital
Kuter, M.D., D. Phil., Oncology
Harvard Medical School; Assistant Physician, Massachusetts General Hospital
C. Shellito, M.D., Surgery
Harvard Medical School; Associate Visiting Surgeon, Massachusetts General Hospital
A. Stern, M.D., Psychiatry
Harvard Medical School; Psychiatrist and Chief, Psychiatric Consultation Service, Massachusetts General Hospital
Peckham, Editorial Director