$Unique_ID{BRK03663} $Pretitle{} $Title{Diabetes, Insulin-Dependent} $Subject{Diabetes Insulin-Dependent Type I Diabetes Juvenile Diabetes Diabetes Mellitus} $Volume{} $Log{} Copyright (C) 1986, 1987, 1990, 1991, 1992 National Organization for Rare Disorders, Inc. 220: Diabetes, Insulin-Dependent ** IMPORTANT ** It is possible the main title of the article (Insulin-Dependent Diabetes) is not the name you expected. Please check the SYNONYMS listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Type I Diabetes Juvenile Diabetes Diabetes Mellitus General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Insulin-dependent Diabetes is a disorder in which the body does not produce enough insulin and is, therefore, unable to convert nutrients into the energy necessary for daily activity. The disorder affects females and males approximately equally. Although the causes of insulin-dependent diabetes are not known, genetic factors seem to play a role. Symptoms Normally, sugars and starches (carbohydrates) in the foods we eat are processed by digestive juices into glucose. Glucose circulates in the blood as a major energy source for body functions. Its use is regulated primarily by insulin, a hormone produced by the pancreas gland (located behind the stomach). In the person with diabetes, there is a malfunction in the production of insulin. There are two main types of diabetes: Type I or Insulin-Dependent and Type II or Noninsulin-Dependent. The insulin-dependent type of diabetes generally has onset during childhood or adolescence, though it can occur at any age. Because the pancreas supplies little or no insulin in this disease, daily injections of the hormone and a controlled diet are necessary to regulate blood sugar levels. Insulin is generally effective in preventing glucose buildup, but it is a treatment and not a cure for diabetes. The onset of Insulin-Dependent Diabetes begins with frequent urination, extreme thirst, constant hunger, and unexplained weight loss. Because people with Type I Diabetes lack sufficient insulin, glucose accumulates in the blood to levels too high for the kidneys to excrete. In an effort to remove the excess sugar, the kidneys excrete large amounts of water as well as essential body elements resulting in frequent urination, thirst, and weakness. Hunger and fatigue are caused by the body's inability to utilize foods properly for nourishment and energy. To find alternate sources of energy, the body turns to its stores of fat and protein, causing weight loss and the accumulation of fat breakdown products (acetone and related acids) in the blood. These metabolites of fat produce increased acidity of the blood, and a potentially fatal condition (ketoacidosis) can result if treatment is not prompt. A child with Type I Diabetes may also fail to grow and develop normally. Diabetics of all ages may experience itching of the skin, changes in vision, and slow healing of cuts and bruises. Medical attention should be sought if any of these symptoms occur. The diabetic condition can result in certain long-term complications which may involve many organs of the body. The blood vessels, nervous system, kidneys and eyes are particularly affected. While successful control of blood glucose levels may reduce the risk of complications, the exact relationship between these factors is not fully understood. Studies are being conducted to determine whether strict blood glucose control plays a significant role in preventing or delaying the onset of complications resulting from diabetes. 1. Cardiovascular Complications. Heart and blood vessel diseases such as heart attack, hardening of the arteries (arteriosclerosis), and stroke are the leading causes of illness, disability and death among diabetics. Persons with diabetes are twice as likely to suffer from coronary heart disease and stroke and five times as likely to suffer from arterial disease of the limbs than the non-diabetic population. Exactly how diabetes damages the cardiovascular system is not yet clear. 2. Diabetic Nephropathy (Kidney Disease). Kidney (renal) disease, or diabetic nephropathy, can be a serious complication of diabetes. Normally, the kidneys cleanse impurities from the blood, but diabetes can cause damage to the blood vessels in the kidney and interfere with this vital process. A procedure called hemodialysis is frequently used to remove waste products from the blood when the kidneys can no longer perform this function adequately. Diabetics with serious renal disease may also be candidates for a kidney transplant if a suitable donor organ is available. 3. Diabetic Neuropathy (damage to the nerves). Diabetes can also cause a complication called Diabetic Neuropathy which is damage to the peripheral nerves. These nerves run throughout the body, connecting the spinal cord to muscles, skin, blood vessels, and all other organs. Most importantly, they serve as the primary link between the central nervous system and the entire body. Diabetes is a common cause of peripheral neuropathy; however, this condition can also result from injury, alcoholism, or other factors. Almost all people with diabetes eventually develop some peripheral nerve involvement, but for many, it is slight and produces no symptoms. For the 10 to 25 percent who suffer from serious neuropathy, it can produce problems such as tingling and numbness in the feet, dizziness, impotence, leg pain and double vision. 4. Diabetic Retinopathy (damaged retina). Diabetes is the leading cause of partial loss of vision and new blindness in the United States today. Generally, diabetes affects the retina of the eye and produces a variety of changes referred to as diabetic retinopathy. Less frequent, but no less serious, are several other eye problems caused by diabetes including cataracts, glaucoma, and optic nerve disease. While many persons with diabetes undergo some changes in the retina, only about 3 percent are seriously threatened with blindness. Today, there are approximately 150,000 Americans who suffer significant visual impairment due to diabetic retinopathy. (For more information on this disorder, choose "Diabetic Retinopathy" as your search term in the Rare Disease Database.) Although the way in which diabetes damages eye tissue is not known, two important treatments have been developed in recent years. The first, laser photocoagulation, uses finely focused beams of laser light to seal off and destroy abnormal retinal vessels and diseased tissues. While this treatment does not prevent diabetic changes from taking place, it has proven beneficial in reducing the risk of severe vision loss in many cases. The second technique, vitrectomy, involves surgical removal of cloudy eye fluids that result from blood vessel hemorrhage. This procedure offers hope to people with severely impaired vision resulting from this form of diabetic retinopathy. Scientists continue to explore better use of these techniques as well as the basic causes of eye damage resulting from diabetes. 5. Complications of Pregnancy. Diabetic women run a greater risk of having babies who are stillborn, die in infancy, and suffer from congenital defects than do non-diabetics. It is not uncommon for infants of diabetic mothers to be larger than normal at birth if maternal blood glucose level is elevated. In fact, this is sometimes a warning sign of diabetes in a woman who has not yet been diagnosed with the disorder. Strict attention to control of diabetes is essential during pregnancy to help reduce risks to both mother and baby. Diabetic emergencies which require prompt medical attention include hypoglycemia and ketoacidosis. Hypoglycemia, also called "insulin reaction" or "insulin shock" can occur if the blood sugar level of the person with diabetes falls too low. This results from too much insulin in the system caused by too large a dose of insulin, overly strenuous exercise, or failure to eat shortly after insulin is taken. Although each person may react differently, common symptoms of insulin reaction include trembling, sweating and nervousness. Some persons with diabetes may experience hunger, headache, nausea, drowsiness, or symptoms similar to inebriation. In severe cases of insulin shock, the person with diabetes may even become unconscious. A careful blend of correct amounts of insulin, exercise and food can usually prevent insulin reaction. When hypoglycemia does occur, however, most people with diabetes sense early warning signals and eat or drink something sweet to raise the amount of sugar in the blood. If a person is unconscious, an injection of glucose solution or the hormone glucagon (which stimulates the production of glucose), should be administered. Ketoacidosis, or Diabetic Coma, results from too little insulin in the system. When the body is unable to use glucose for fuel, it draws on its own stores of protein and fat for energy. Acids, or ketones, produced by the excessive breakdown of fat then accumulate in the blood stream quicker than the kidneys can excrete them. Unlike hypoglycemia, the symptoms of ketoacidosis develop slowly over a period of days. The person with diabetes may begin to experience abdominal pain, nausea, vomiting, rapid breathing and drowsiness. If left untreated, ketoacidosis can progress to coma and death. Ketoacidosis can be prevented by careful daily evaluation of insulin needs. Particularly stressful situations such as illness or surgery may require increased amounts of insulin. Most importantly, a person with diabetes should never skip or delay an insulin injection and should pay careful attention to his/her diet. A survey by the U.S. Department of Health, Education and Welfare during 1960 to 1962 on forty-four million adults showed that men and women with diabetes ran a higher than average risk of periodontal disease. Causes The exact causes of Insulin-Dependent Diabetes are not known although most types of diabetes are known to have hereditary factors. Scientists believe that both heredity and environment may play important roles in the development of diabetes. Research suggests that certain viruses, in combination with genetic susceptibility and other unknown environmental factors, may trigger the onset of some types of this disorder. High levels of growth hormone in adolescents and adults under stress may also stimulate the production of glucose by the liver. Affected Population Onset of Insulin-Dependent Diabetes usually occurs before 40 years of age; onset of this type of Diabetes in late adulthood is less common, but it can occur. The disorder affects females and males approximately equally. Two million Americans may be affected by this disorder. Related Disorders Type II Diabetes (Non-Insulin Dependent Diabetes Mellitus) is the more common form of the disorder. Also known as Adult Onset Diabetes, it usually occurs after the age of 40 years. This type of diabetes is not secondary to other diseases or conditions. In many cases, the disorder can be controlled through diet, regular exercise, and sometimes, with oral medications (e.g., chlorpropamide, glypizide, or glyburide). Some scientists believe that people with non-insulin dependent diabetes do not convert glucose (sugar) into its starch-like storage form, glycogen, at the same rate as normal people. Glucose is converted in the muscles. This means that there may be two defects in people with non-insulin dependent diabetes. Glucose may not get into muscle cells normally. The beta cells in the pancreas, which respond to blood glucose levels, work overtime to increase their secretion of insulin. Over a long period of time the beta cells can't keep up their high pace, and they begin to fail. This can cause insulin-dependent diabetes. Therapies: Standard A daily routine of insulin-injection, controlled diet, exercise to burn off glucose, and testing for blood sugar level is vital in achieving and maintaining good blood sugar control in patients with Insulin-Dependent Diabetes. Urine testing for glucose spillage had been a standard recommendation in past years, but has now been replaced with self blood glucose testing. Self monitoring of blood glucose levels uses a single drop of blood which is obtained with a finger stick, and placed on a chemically treated pad on a plastic strip; the color change of the chemically treated pad is compared to a color chart or "read" by a battery operated portable meter. Insulin must be given by injection, usually two or more times each day. Recently portable "insulin pumps" have been developed, which permit continuous administration of insulin, as well as additional amounts of insulin when needed to control the changes in blood sugar level that occurs after meals. Therapies: Investigational In recent years, research supported by the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), and other components of the National Institutes of Health, and non profit agencies (See Resources) that fund scientific research on diabetes has yielded new and exciting information on the possible causes and improved management of diabetes and its complications. Scientists have now identified genetic factors that appear to be associated with diabetes - a finding that could lead to methods of prevention of the disorder in genetically susceptible persons. In related studies, the discovery that the insulin-producing beta cells can be infected and destroyed by common viruses could eventually result in the development of a vaccine to prevent diabetes. Pancreas transplantation has had limited success, primarily due to the problem of rejection. However, recent advances in immunology have raised hopes that the problem of rejection reaction common in organ transplantation may be altered or prevented. These findings increase the possibility of transplanting healthy insulin-producing cells to correct the diabetic condition. Recently, a clinical study to assess the effectiveness of a programmable implantable insulin pump for unstable diabetes has been funded by FDA's Orphan Product Grant program. This orphan device is being studied at the University of California at Irvine, CA by Dr. M. Arthur Charles. Although these advances hold great promise for the future, it is important to recognize that they are still in the research phase and are not part of the routine treatment of diabetes. Exciting research on all aspects of diabetes is now being conducted at medical institutions throughout the United States and abroad. The association of heredity, viral infections, the presence of high levels of growth hormone, and immunology has provided new leads in the treatment and gives hope for ultimate prevention of diabetes. New information, based on experiments on mice, has shed new light on the understanding in insulin secretion. The signaling process between glucose stimulation and insulin secretion seems to be under the direct influence of calcium in the cell. How and why insulin secretion is disrupted in diabetes and how this disruption can be prevented or repaired could help lead to finding a cure for diabetes. Scientists are investigating how precise control of diabetes compares to the usual therapies for diabetes in order to learn how best to prevent or delay the serious complications of the disorder. To participate in the Diabetes Control and Complications Trial (DCCT), a person must be between 13 and 39 years of age; had Insulin-Dependent Diabetes for at least one year but not more than 15 years; not have any severe complications such as eye or kidney disease; and not be taking more than 2 insulin injections per day or using an insulin pump. For more information on this study, call: (800) 522- DCCT. This research project is sponsored by the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK). Transplanting a whole pancreas or a segment of one shows promise in restoring normal insulin production in some Diabetes patients. More than 1,000 pancreas transplants have been performed worldwide, with varying degrees of success. Immunosuppressive drug treatment following transplantation may consists of a combination of cyclosporine, prednisone, and azathioprine (Aza), although these drugs may be slightly toxic in large doses. Because transplant patients will have to undergo a lifetime of immunosuppression, this procedure is recommended only for individuals whose complications are more severe than those caused by immunosuppression. A new therapy aimed at treating persons who may become diabetic in a few years by giving them the immunosuppression drug Imuran is under investigation. More study is necessary to determine the long-term safety and effectiveness of this form of treatment. Clinical trials are underway to study pancreas transplantation and the monitoring of graft function. Interested persons may wish to contact: Dr. A. Osama Gaber University of Tennessee - Memphis 956 Court Ave., Suite G212 Memphis, TN 38163 (901) 528-5924 to see if further patients are needed for this research. Clinical trials are underway to study molecular genetics of heritable insulin resistance (A). Interested persons may wish to contact: Louis J. Elsas, II, M.D. Emory University, Dept. of Pediatrics 2040 Rigewood Dr. Atlanta, GA 30322 (404) 727-5863 to see if further patients are needed for this research. Clinical trials are underway to study the genetic location causing non-insulin diabetes and especially neonatal diabetes. Interested persons may wish to contact: Dr. M. Alan Permutt Washington University School of Medicine Metabolic Division 660 S. Euclid St. Louis, MO 63110 (314) 362-8680 to see if further patients are needed for this research. This disease entry is based upon medical information available through January 1992. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Insulin-Dependent Diabetes, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 American Diabetes Association National Service Center 1660 Duke St. Alexandria, VA 22314 (703) 549-1000 (800) ADA-DISC (800) 232-3472) Juvenile Diabetes Foundation International 60 Madison Avenue, 4th Floor New York, NY 10010 (212) 889-7575 National Diabetes Information Clearinghouse Box NDIC Bethesda, MD 20892 (301) 468-2162 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References CECIL TEXTBOOK OF MEDICINE, 18th ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Eds.: W. B. Saunders Co., 1988. Pp. 1360-81. THE MERCK MANUAL 15th ed: R. Berkow, et al: eds; Merck, Sharp & Dohme Research Laboratories, 1987. Pp. 1069-71. MUSCLES PINPOINTED AS SITE OF DIABETIC DEFECT, Collins, J., Research Resources Reporter, (September 1990, issue 14 (9)). Pp. 1-3.