diabetes mellitus

Diabetes Why managing blood sugar is so important.

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Definition

Diabetes mellitus is a condition in which the pancreas no longer produces enough insulin or when cells stop responding to the insulin that is produced, so that glucose in the blood cannot be absorbed into the cells of the body. Symptoms include frequent urination, lethargy, excessive thirst, and hunger. The treatment includes changes in diet, oral medications, and in some cases, daily injections of insulin.

Description

Diabetes mellitus is a chronic disease that causes serious health complications including renal (kidney) failure, heart disease, stroke, and blindness. Approximately 14 million Americans (about 5% of the population) have diabetes. Unfortunately, as many as one-half are unaware that they have it.

Every cell in the human body needs energy in order to function. The body's primary energy source is glucose, a simple sugar resulting from the digestion of foods containing carbohydrates (sugars and starches). Glucose from the digested food circulates in the blood as a ready energy source for any cells that need it. Insulin is a hormone or chemical produced by cells in the pancreas, an organ located behind the stomach. Insulin bonds to a receptor site on the outside of cell and acts like a key to open a doorway into the cell through which glucose can enter. Some of the glucose can be converted to concentrated energy sources like glycogen or fatty acids and saved for later use. When there is not enough insulin produced or when the doorway no longer recognizes the insulin key, glucose stays in the blood rather entering the cells.

The body will attempt to dilute the high level of glucose in the blood, a condition called hyperglycemia, by drawing water out of the cells and into the bloodstream in an effort to dilute the sugar and excrete it in the urine. It is not unusual for people with undiagnosed diabetes to be constantly thirsty, drink large quantities of water, and urinate frequently as their bodies try to get rid of the extra glucose. This creates high levels of glucose in the urine.

At the same time that the body is trying to get rid of glucose from the blood, the cells are starving for glucose and sending signals to the body to eat more food, thus making patients extremely hungry. To provide energy for the starving cells, the body also tries to convert fats and proteins to glucose. The breakdown of fats and proteins for energy causes acid compounds called ketones to form in the blood. Ketones will also be excreted in the urine. As ketones build up in the blood, a condition called ketoacidosis can occur. This condition can be life threatening if left untreated, leading to coma and death.

Type I diabetes, sometimes called juvenile diabetes, begins most commonly in childhood or adolescence. In this form of diabetes, the body produces little or no insulin. It is characterized by a sudden onset and occurs more frequently in populations descended from Northern European countries (Finland, Scotland, Scandinavia) than in those from Southern European countries, the Middle East, or Asia. In the United States, approximately three people in 1,000 develop Type I diabetes. This form is also called insulin-dependent diabetes because people who develop this type need to have daily injections of insulin.

Brittle diabetics are a subgroup of Type I where patients have frequent and rapid swings of blood sugar levels between hyperglycemia (a condition where there is too much glucose or sugar in the blood) and hypoglycemia (a condition where there is abnormally low levels of glucose or sugar in the blood). These patients may require several injections of different types of insulin during the day to keep the blood sugar level within a fairly normal range.

The more common form of diabetes, Type II, occurs in approximately 3–5% of Americans under 50 years of age, and increases to 10–15% in those over 50. More than 90% of the diabetics in the United States are Type II diabetics. Sometimes called age-onset or adult-onset diabetes, this form of diabetes occurs most often in people who are overweight and who do not exercise. It is also more common in people of Native American, Hispanic, and African-American descent. People who have migrated to Western cultures from East India, Japan, and Australian Aboriginal cultures are also more likely to develop Type II diabetes than those who remain in their original countries.

Type II is considered a milder form of diabetes because of its slow onset (sometimes developing over the course of several years) and because it can usually be controlled with diet and oral medication. The consequences of uncontrolled and untreated Type II diabetes, however, are the just as serious as those for Type I. This form is also called noninsulin-dependent diabetes, a term that is somewhat misleading. Many people with Type II diabetes can control the condition with diet and oral medications, however, insulin injections are sometimes necessary if treatment with diet and oral medication is not working.

Another form of diabetes called gestational diabetes can develop during pregnancy and generally resolves after the baby is delivered. This diabetic condition develops during the second or third trimester of pregnancy in about 2% of pregnancies. The condition is usually treated by diet, however, insulin injections may be required. These women who have diabetes during pregnancy are at higher risk for developing Type II diabetes within 5–10 years.

Diabetes can also develop as a result of pancreatic disease, alcoholism, malnutrition, or other severe illnesses that stress the body.

— Altha Roberts Edgren

Dictionary: diabetes mel·li·tus   (mə-lī'təs, mĕl'ĭ-)

Top

1. A severe, chronic form of diabetes caused by insufficient production of insulin and resulting in abnormal metabolism of carbohydrates, fats, and proteins. The disease, which typically appears in childhood or adolescence, is characterized by increased sugar levels in the blood and urine, excessive thirst, frequent urination, acidosis, and wasting. Also called insulin-dependent diabetes, type 1 diabetes.
2. A mild form of diabetes that typically appears first in adulthood and is exacerbated by obesity and an inactive lifestyle. This disease often has no symptoms, is usually diagnosed by tests that indicate glucose intolerance, and is treated with changes in diet and an exercise regimen. Also called non-insulin-dependent diabetes, type 2 diabetes.

[New Latin diabētēs mellītus : Latin diabētēs, diabetes + Latin mellītus, honey-sweet.]

A metabolic disorder caused primarily by a defect in the production of insulin by the islet cells of the pancreas resulting in an inability to use carbohydrates. Characterized by hyperglycemia, glycosuria, polyuria, hyperlipemia (caused by imperfect catabolism of fats), acidosis, ketonuria, and a lowered resistance to infection. Periodontal manifestations may include recurrent and multiple periodontal abscesses, osteoporotic changes in alveolar bone, fungating masses of granulation tissue protruding from periodontal pockets, a lowered resistance to infection, and delay in healing after periodontal therapy.

Definition

Diabetes mellitus is a condition in which the pancreas no longer produces enough insulin or when cells stop responding to the insulin that is produced, so that glucose in the blood cannot be absorbed into the cells of the body. Symptoms include frequent urination, tiredness, excessive thirst, and hunger.

Description

Diabetes mellitus is a chronic disease that causes serious health complications including renal (kidney) failure, heart disease, stroke, and blindness. Approximately 14 million Americans (about 5% of the population) have diabetes. Unfortunately, as many as one-half of them are unaware that they have it.

Background

Every cell in the human body needs energy in order to function. The body's primary energy source is glucose, a simple sugar resulting from the digestion of foods containing carbohydrates (sugars and starches). Glucose from the digested food circulates in the blood as a ready energy source for cells. Insulin is a hormone or chemical produced by cells in the pancreas, an organ located behind the stomach. Insulin binds to receptor sites on the outside of cells and acts like a key to open a door-way

into the cell through which glucose can enter. Some of the glucose can be converted to concentrated energy sources like glycogen or fatty acids and saved for later use. When there is not enough insulin produced or when the doorway no longer recognizes the insulin key, glucose stays in the blood instead of entering the cells.

The body will attempt to dilute the high level of glucose in the blood, a condition called hyperglycemia, by drawing water out of the cells and into the bloodstream. The excess sugar is excreted in the urine. It is not unusual for people with undiagnosed diabetes to be constantly thirsty, to drink large quantities of water, and to urinate frequently as their bodies try to get rid of the extra glucose. This creates high levels of glucose in the urine.

At the same time that the body is trying to get rid of glucose from the blood, the cells are starving for glucose and sending signals to the body to eat more food, thus making patients extremely hungry. To provide energy for the starving cells, the body also tries to convert fats and proteins to glucose. The breakdown of fats and proteins for energy causes acid compounds called ketones to form in the blood. Ketones also will be excreted in the urine. As ketones build up in the blood, a condition called ketoacidosis can occur. If left untreated, ketoacidosis can lead to coma and death.

Types of Diabetes Mellitus

Type I diabetes, sometimes called juvenile diabetes, begins most commonly in childhood or adolescence. In this form of diabetes, the body produces little or no insulin. It is characterized by a sudden onset and occurs more frequently in populations descended from northern European countries (Finland, Scotland, Scandinavia) than in those from southern European countries, the Middle East, or Asia. In the United States, approximately 3 people in 1,000 develop Type I diabetes. This form also is called insulin-dependent diabetes because people who develop this type need to have injections of insulin 1–2 times per day.

Brittle diabetics are a subgroup of Type I where patients have frequent and rapid swings of blood sugar levels between hyperglycemia (a condition where there is too much glucose or sugar in the blood) and hypoglycemia (a condition where there are abnormally low levels of glucose or sugar in the blood). These patients may require several injections of different types of insulin or an insulin pump during the day to keep their blood sugar within a fairly normal range.

The more common form of diabetes, Type II, occurs in approximately 3–5% of Americans under 50 years of age, and increases to 10–15% in those over 50. More than 90% of the diabetics in the United States are Type II diabetics. In 2003, a report noted that nearly one-third of the U.S. population over age 20 has this form of diabetes but remains undiagnosed. Sometimes called age-onset or adult-onset diabetes, this form of diabetes occurs most often in people who are overweight and do not exercise. It also is more common in people of Native American, Hispanic, and African-American descent. People who have migrated to Western cultures from East India, Japan, and Australian Aboriginal cultures are also more likely to develop Type II diabetes than those who remain in their original countries.

Type II is considered a milder form of diabetes because of its slow onset (sometimes developing over the course of several years) and because it can usually be controlled with diet and oral medication. The consequences of uncontrolled and untreated Type II diabetes, however, are just as serious as those for Type I. This form also is called noninsulin-dependent diabetes, a term that is somewhat misleading. Many people with Type II diabetes can control the condition with diet and oral medications, however, insulin injections sometimes are necessary.

Another form of diabetes, called gestational diabetes, can develop during pregnancy and generally resolves after the baby is delivered. This diabetic condition develops during the second or third trimester of pregnancy in about 2% of pregnancies. The condition usually is treated by diet, however, insulin injections may be required. Women who have diabetes during pregnancy are at higher risk for developing Type II diabetes within 5–10 years.

Diabetes also can develop as a result of pancreatic disease, alcoholism, malnutrition, or other severe illnesses that stress the body.

Causes & Symptoms

The causes of diabetes mellitus are unclear, however, there seem to be both hereditary (genetic factors passed on in families) and environmental factors involved. Research has shown that some people who develop diabetes have common genetic markers. In Type I diabetes, an autoimmune response is believed to be triggered by a virus or another microorganism that destroys the cells that produce insulin. In Type II diabetes, age, obesity, and family history of diabetes play a role.

In Type II diabetes, the pancreas may produce enough insulin, however, cells have become resistant to the insulin produced and it may not work as effectively. Symptoms of Type II diabetes can begin so gradually that a person may not know that he or she has it. Early signs are tiredness, extreme thirst, and frequent urination. Other symptoms may include sudden weight loss, slow wound healing, urinary tract infections, gum disease, or blurred vision. It is not unusual for Type II diabetes to be detected while a patient is seeing a doctor about a health concern that was caused by the yet undiagnosed diabetes.

Individuals who are at high risk of developing Type II diabetes mellitus include people who:

• are obese (more than 20% above their ideal body weight)
• have a relative with diabetes mellitus
• belong to a high-risk ethnic population (African-American, Native American, Hispanic, or Native Hawaiian)
• have been diagnosed with gestational diabetes or have delivered a baby weighing more than 9 lb (4 kg)
• have high blood pressure (140/90 mmHg or above)
• have a high density lipoprotein cholesterol level less than or equal to 35 mg/dL and/or a triglyceride level greater than or equal to 250 mg/dL
• have had impaired glucose tolerance or impaired fasting glucose on previous testing

Several common medications can impair the body's use of insulin, causing a condition known as secondary diabetes. These medications include treatments for high blood pressure (furosemide, clonidine, and thiazide diuretics), drugs with hormonal activity (oral contraceptives, thyroid hormone, progestins, and glucocorticorids), and the anti-inflammation drug indomethacin. Several drugs that are used to treat mood disorders (such as anxiety and depression) also can impair glucose absorption. These drugs include haloperidol, lithium carbonate, phenothiazines, tricyclic antidepressants, and adrenergic agonists. Other medications that can cause diabetes symptoms include isoniazid, nicotinic acid, cimetidine, and heparin.

Symptoms of diabetes can develop suddenly (over days or weeks) in previously healthy children or adolescents, or can develop gradually (over several years) in overweight adults over the age of 40. The classic symptoms include feeling tired and sick, frequent urination, excessive thirst, excessive hunger, and weight loss.

Ketoacidosis, a condition due to starvation or un-controlled diabetes, is common in Type I diabetes. Ketones are acid compounds that form in the blood when the body breaks down fats and proteins. Symptoms include abdominal pain, vomiting, rapid breathing, extreme tiredness, and drowsiness. Patients with ketoacidosis will also have a sweet breath odor. Left untreated, this condition can lead to coma and death.

With Type II diabetes, the condition may not become evident until the patient presents for medical treatment for some other condition. A patient may have heart disease, chronic infections of the gums and urinary tract, blurred vision, numbness in the feet and legs, or slow-healing wounds. Women may experience genital itching.

Diagnosis

Diabetes is suspected based on symptoms. Urine tests and blood tests can be used to confirm a diagnosis of diabetes based on the amount of glucose in the urine and blood. Urine tests also can detect ketones and protein in the urine which may help diagnose diabetes and assess how well the kidneys are functioning. These tests also can be used to monitor the disease once the patient is under treatment.

Urine Tests

Clinistix and Diastix are paper strips or dipsticks that change color when dipped in urine. The test strip is compared to a chart that shows the amount of glucose in the urine based on the change in color. The level of glucose in the urine lags behind the level of glucose in the blood. Testing the urine with a test stick, paper strip, or tablet is not as accurate as blood testing, however it can give a fast and simple reading.

Ketones in the urine can be detected using similar types of dipstick tests (Acetest or Ketostix). Ketoacidosis can be a life-threatening situation in Type I diabetics, so having a quick and simple test to detect ketones can assist in establishing a diagnosis sooner.

Another dipstick test can determine the presence of protein or albumin in the urine. Protein in the urine can indicate problems with kidney function and can be used to track the development of renal failure. A more sensitive test for urine protein uses radioactively tagged chemicals to detect microalbuminuria, small amounts of protein in the urine, which may not show up on dipstick tests.

Blood Tests

Fasting glucose test. Blood is drawn from a vein in the patient's arm after the patient has not eaten for at least eight hours, usually in the morning before breakfast. The red blood cells are separated from the sample and the amount of glucose is measured in the remaining plasma. A plasma level of 7.8 mmol/L (200 mg/L) or greater can indicate diabetes. The fasting glucose test is usually repeated on another day to confirm the results.

Postprandial glucose test. Blood is taken right after the patient has eaten a meal.

Oral glucose tolerance test. Blood samples are taken from a vein before and after a patient drinks a sweet syrup of glucose and other sugars. In a non-diabetic, the level of glucose in the blood goes up immediately after the drink and then decreases gradually as insulin is used by the body to metabolize, or absorb, the sugar. In a diabetic, the glucose in the blood goes up and stays high after drinking the sweetened liquid. A plasma glucose level of 11.1 mmol/L (200 mg/dL) or higher at two hours after drinking the syrup and at one other point during the two-hour test period confirms the diagnosis of diabetes.

A diagnosis of diabetes is confirmed if a plasma glucose level of at least 11.1 mmol/L, a fasting plasma glucose level of at least 7 mmol/L; or a two-hour plasma glucose level of at least 11.1 mmol/L during an oral glucose tolerance test.

In 2002, scientists announced that a new simple blood test to screen for diabetes had been developed. Prior to that time, community-wide screening procedures had not proven cost-effective. The new screening test proved cost-effective if conducted in physician offices on patients with three known risk factors of obesity, self-reported high blood pressure, and family history of diabetes.

Home blood glucose monitoring kits are available so diabetics can monitor their own levels. A small needle or lancet is used to prick the finger and a drop of blood is collected and analyzed by a monitoring device. Some patients may test their blood glucose levels several times during a day and use this information to adjust their diet or doses of insulin.

Treatment

There is currently no cure for diabetes. Diet, exercise, and careful monitoring of blood glucose levels are the keys to manage diabetes so that patients can live a relatively normal life. Diabetes can be life-threatening if not properly managed, so patients should not attempt to treat this condition without medical supervision. Treatment of diabetes focuses on two goals: keeping blood glucose within normal range and preventing the development of long-term complications. Alternative treatments cannot replace the need for insulin but they may enhance insulin's effectiveness and may lower blood glucose levels. In addition, alternative medicines may help to treat complications of the disease and improve quality of life.

Diet

Diet and moderate exercise are the first treatments implemented in diabetes. For many Type II diabetics, weight loss may be an important goal to help them to control their diabetes. A well-balanced, nutritious diet provides approximately 50–60% of calories from carbohydrates, approximately 10–20% of calories from protein, and less than 30% of calories from fat. The number of calories required depends on the patient's age, weight, and activity level. The calorie intake also needs to be distributed over the course of the entire day so surges of glucose entering the blood system are kept to a minimum. In 2002, a Korean study demonstrated that eating a combination of whole grains and legume powder was beneficial in lowering blood glucose levels in men with diabetes.

Keeping track of the number of calories provided by different foods can be complicated, so patients are usually advised to consult a nutritionist or dietitian. An individualized, easy-to-manage diet plan can be set up for each patient. Both the American Diabetes Association and the American Dietetic Association recommend diets based on the use of food exchange lists. Each food exchange contains a known amount of calories in the form of protein, fat, or carbohydrate. A patient's diet plan will consist of a certain number of exchanges from each food category (meat or protein, fruits, breads and starches, vegetables, and fats) to be eaten at meal times and as snacks. Patients have flexibility in choosing the foods they eat as long as they don't exceed the number of exchanges prescribed. The food exchange system, along with a plan of moderate exercise, can help diabetics lose excess weight and improve their overall health. Certain foods will be emphasized over others to promote a healthy heart as well.

Supplements

CHROMIUM PICOLINATE. Several studies have had conflicting results on the effectiveness of chromium picolinate supplementation for control of blood glucose levels. In one study, approximately 70% of the diabetics receiving 200 micrograms of chromium picolinate daily reduced their need for insulin and medications. While some studies have shown that supplementation caused significant weight loss, and decreases in blood glucose and serum triglycerides, others have shown no benefit. Chromium supplementation may cause hypoglycemia and other side effects.

MAGNESIUM. Magnesium deficiency may interfere with insulin secretion and uptake and worsen the patient's control of blood sugar. Also, magnesium deficiency puts diabetics at risk for certain complications, especially retinopathy and cardiovascular disease.

VANADIUM. Vanadium has been shown to bring blood glucose to normal levels in diabetic animals. Also, people who took vanadium were able to decrease their need for insulin.

Chinese Medicine

Non-insulin dependent diabetics who practiced daily qigong for one year had decreases in fasting blood glucose and blood insulin levels. Acupuncture may relieve pain in patients with diabetic neuropathy. Acupuncture also may help to bring blood glucose to normal levels in diabetics who do not require insulin.

Best when used in consultation with a Chinese medicine physician, some Chinese patent medicines that alleviate symptoms of or complications from diabetes include:

• Xiao Ke Wan (Emaciation and Thirst Pill) for diabetics with increased levels of sugar in blood and urine.
• Yu Quan Wan (Jade Spring Pill) for diabetics with a deficiency of Yin.
• Liu Wei Di Huang Wan (Six Ingredient Pill with Rehmannia) for stabilized diabetics with a deficiency of Kidney Yin.
• Jin Gui Shen Wan (Kidney Qi Pill) for stabilized diabetics with a deficiency of Kidney Yang.

Herbals

Herbal medicine can have a positive effect on blood glucose and quality of life in diabetics. The results of clinical study of various herbals are:

• Wormwood (Artemisia herba-alba) decreased blood glucose.
• Gurmar (Gymnema sylvestre) decreased blood glucose levels and the need for insulin.
• Coccinia indica improved glucose tolerance.
• Fenugreek seed powder (Trigonella foenum graecum) decreased blood glucose and improved glucose tolerance.
• Bitter melon (Momordica charantia) decreased blood glucose and improved glucose tolerance.
• Cayenne pepper (Capsicum frutescens) can help relieve pain in the peripheral nerves (a type of diabetic neuropathy).

Other herbals that may treat or prevent diabetes and its complications include:

• Bilberry (Vaccinium myrtillus) may lower blood glucose levels and maintain healthy blood vessels.
• Garlic (Allium sativum) may lower blood sugar and cholesterol levels.
• Onions (Allium cepa) may help lower blood glucose levels.
• Ginkgo (Ginkgo biloba) improves blood circulation.

Yoga

Studies of diabetics have shown that practicing yoga leads to decreases in blood glucose, increased glucose tolerance, decreased need for diabetes medications, and improved insulin processes. Yoga also enhances the sense of well-being.

Biofeedback

Many studies have been performed to test the benefit of adding biofeedback to the diabetic's treatment plan. Relaxation techniques, such as visualization, usually were included. Biofeedback can have significant effects on diabetes including improved glucose tolerance and decreased blood glucose levels. In addition, biofeedback can be used to treat diabetic complications and improve quality of life.

Allopathic Treatment

Traditional treatment of diabetes begins with a well balanced diet and moderate exercise. Medications are prescribed only if the patient's blood glucose cannot be controlled by these methods.

Oral Medications

Oral medications are available to lower blood glucose in Type II diabetics. Drugs first prescribed for Type II diabetes are in a class of compounds called sulfonylureas and include tolbutamide, tolazamide, acetohexamide, chlorpropamide, glyburide, glimeperide, and glipizide. The way that these drugs work is not well understood, however, they seem to stimulate cells of the pancreas to produce more insulin. New medications that are available to treat diabetes include metformin, acarbose, and troglitizone. These medications are not a substitute for a well planned diet and moderate exercise. Oral medications are not effective for Type I diabetes, in which the patient produces little or no insulin.

Insulin

Patients with Type I diabetes need daily injections of insulin to help their bodies use glucose. Some patients with Type II diabetes may need to use insulin injections if their diabetes cannot be controlled. Injections are given subcutaneously—just under the skin, using a small needle and syringe. Purified human insulin is most commonly used, however, insulin from beef and pork sources also is available. Insulin may be given as an injection of a single dose of one type of insulin once a day. Different types of insulin can be mixed and given in one dose or split into two or more doses during a day. Patients who require multiple injections over the course of a day may be able to use an insulin pump that administers small doses of insulin on demand. In 2002, reports announced that early research shows a synthetic insulin called insulin glargine might show promise for patients at risk for hypoglycemia from insulin therapy. Clinical trials showed that when used in combination with certain other short-acting insulins, it safely regulated blood glucose for longer durations and was well tolerated by patients.

Hypoglycemia, or low blood sugar, can be caused by too much insulin, too little food (or eating too late to coincide with the action of the insulin), alcohol consumption, or increased exercise. A patient with symptoms of hypoglycemia may be hungry, sweaty, shaky, cranky, confused, and tired. Left untreated, the patient can lose consciousness or have a seizure. This condition is sometimes called an insulin reaction and should be treated by giving the patient something sweet to eat or drink like candy, sugar cubes, or juice.

Surgery

Transplantation of a healthy pancreas into a diabetic patient is a successful treatment, however, this transplant usually is done only if a kidney transplant is performed at the same time. It is not clear if the potential benefits of transplantation outweigh the risks of the surgery and subsequent drug therapy.

Expected Results

Uncontrolled diabetes is a leading cause of blindness, end-stage renal disease, and limb amputations. It also doubles the risk of heart disease and increases the risk of stroke. Eye problems including cataracts, glaucoma, and retinopathy also are more common in diabetics. Kidney disease is a common complication of diabetes and may require kidney dialysis or a kidney transplant. Babies born to diabetic mothers have an increased risk of birth defects and distress at birth.

Diabetic peripheral neuropathy is a condition where nerve endings, particularly in the legs and feet, become less sensitive. Diabetic foot ulcers are a problem since the patient does not feel the pain of a blister, callous, or other minor injury. Poor blood circulation in the legs and feet contributes to delayed wound healing. The inability to sense pain along with the complications of delayed wound healing can result in minor injuries, blisters, or callouses becoming infected and difficult to treat. Severely infected tissue breaks down and rots, often necessitating amputation of toes, feet, or legs.

Prevention

Research continues on ways to prevent diabetes and to detect those at risk for developing diabetes. While the onset of Type I diabetes is unpredictable, the risk of developing Type II diabetes can be reduced by maintaining ideal weight and exercising regularly. The physical and emotional stress of surgery, illness, and alcoholism can increase the risks of diabetes, so maintaining a healthy lifestyle is critical to preventing the onset of Type II diabetes and preventing further complications of the disease.

In early 2002, researchers announced that patients at high risk for developing diabetes who took an ACE inhibitor called ramipril reduced their risk of developing diabetes substantially. Another report at Duke University showed that sustained intensive exercise could forestall development of diabetes or cardiovascular disease in high-risk patients. The benefits of long-term exercise even continue one month after exercising stops. In 2003, advances in genetics found a key gene that may explain why some people are more susceptible to the disease than others.

Resources

Books

Foster, Daniel W. "Diabetes Mellitus." In Harrison's Principles of Internal Medicine. 14th ed. Edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.

Garber, Alan J. "Diabetes Mellitus." In Internal Medicine. Edited by Jay H. Stein, et al. St. Louis: Mosby, 1998.

Karam, John H. "Diabetes Mellitus & Hypoglycemia." In Current Medical Diagnosis & Treatment 1998. 37th ed. Edited by L.M. Tierney, Jr., S.J. McPhee, and M.A. Papadakis. Stamford, CT: Appleton & Lange, 1998.

McGrady, Angele and James Horner. "Complementary/Alternative Therapies in General Medicine: Diabetes Mellitus." In Complementary/Alternative Medicine: An Evidence Based Approach. Edited by John W. Spencer and Joseph J. Jacobs. St. Louis: Mosby, 1999.

Sherwin, Robert S. "Diabetes Mellitus." In Cecil Textbook of Medicine. 20th ed. Edited by J. Claude Bennett and Fred Plum. Philadelphia, PA: W.B. Saunders Company, 1996.

Smit, Charles Kent, John P. Sheehan, and Margaret M. Ulchaker. "Diabetes Mellitus." In Family Medicine, Principles and Practice. 5th ed. Edited by Robert B. Taylor. New York: Springer-Verlag, 1998.

Ying, Zhou Zhong and Jin Hui De. "Endocrinology." In Clinical Manual of Chinese Herbal Medicine and Acupuncture. New York: Churchill Livingston, 1997.

Periodicals

"Exercise Can Forestall Diabetes in At-Risk Patients." Diabetes Week (March 25, 2002):2.

Fox, Gary N., and Zijad Sabovic. "Chromium Picolinate Supplementation for Diabetes Mellitus." The Journal of Family Practice 46 (1998): 83-86.

Hartnett, Terry."Early Results Show Promise for Synthetic Insulin." Diabetes Week (March 18, 2002):4.

Jenkins, David JA, et al."Type 2 Diabetes and the Vegetarian Diet." American Journal of Clinical Nutrition (September 2003):610S.

"Mouse, Stripped of a Key Gene, Resists Diabetes." Biotech Week (September 24, 2003):557.

"Nearly One-third of Diabetes Undiganosed, According to New Government Data." Medical Letter on the CDC & FDA (September 28, 2003):13.

"Ramipril Cuts Diabetes Risk." Family Practice News 32, no. 3 (February 1, 2002):10.

"Simple Blood Test Could Detect New Cases of Diabetes." Diabetes Week (January 21, 2002):4.

"Whole Grain and Legume Powder Diet Benefits Diabetics and the Healthy." Diabetes Week (January 7, 2002):8.

"Trends in the Prevalence and Incidence of Self-Reported Diabetes Mellitus-United States, 1980-1994." Morbidity & Mortality Weekly Report 46 (1997): 1014-1018.

"Updated Guidelines for the Diagnosis of Diabetes in the US." Drugs & Therapy Perspectives 10 (1997): 12-13.

Organizations

American Diabetes Association. 1660 Duke Street, Alexandria, VA 22314. (703) 549-1500. Diabetes Information and Action Line: (800) DIABETES. http://www.diabetes.org.

American Dietetic Association. 430 North Michigan Avenue, Chicago, IL 60611. (312) 822-0330. http://www.eatright.org.

Juvenile Diabetes Foundation International. 120 Wall Street, New York, NY 10005-4001. (212) 785-9595. (800) JDF-CURE.

National Diabetes Information Clearinghouse. 1 Information Way, Bethesda, MD 20892-3560. (301) 654-3327.

National Institutes of Health. National Institute of Diabetes, Digestive and Kidney Diseases. 9000 Rockville Pike, Bethesda, MD 20892. (301) 496-3583. http://www.niddk.nih.gov.

Other

Centers for Disease Control and Prevention Diabetes. http://www.cdc.gov/nccdphp/ddt/ddthome.htm.

"Insulin-Dependent Diabetes." National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health, NIH Publication No. 94-2098.

"Noninsulin-Dependent Diabetes." National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health, NIH Publication No. 92-241.

[Article by: Belinda Rowland; Teresa G. Odle]

Definition

Diabetes mellitus is a chronic disease in which the body is not able to correctly process glucose for cell energy due to either an insufficient amount of the hormone insulin or a physical resistance to the insulin the body does produce. Without proper treatment through medication and/or lifestyle changes, the high blood glucose (or blood sugar) levels caused by diabetes can cause long-term damage to organ systems throughout the body.

Description

There are three types of diabetes mellitus: type 1 (also called juvenile diabetes or insulin-dependent diabetes), type 2 (also called adult-onset diabetes), and gestational diabetes. While type 2 is the most prevalent, consisting of 90 to 95 percent of diabetes patients in the United States, type 1 diabetes is more common in children. Gestational diabetes occurs in pregnancy and resolves at birth.

Every cell in the human body needs energy in order to function. The body's primary energy source is glucose, a simple sugar resulting from the digestion of foods containing carbohydrates (primarily sugars and starches). Glucose from the digested food circulates in the blood as a ready energy source for any cells that need it. However, glucose requires insulin in order to be processed for cellular energy.

Insulin is a hormone or chemical produced by cells in the pancreas, an organ located behind the stomach. Insulin bonds to a receptor site on the outside of a cell. It acts like a key to open a doorway into the cell through which glucose can enter. When there is not enough insulin produced (as is the case with type 1 diabetes) or when the doorway no longer recognizes the insulin key (which happens in type 2 and gestational diabetes), glucose stays in the bloodstream rather entering the cells. The high blood glucose, or blood sugar, levels that result are known as hyperglycemia.

Type 1 Diabetes

Type 1 diabetes occurs when the beta cells of the pancreas are damaged and stop producing the hormone insulin. While the exact cause of this cell damage is not completely understood, it is thought to be a combination of environmental and autoimmune factors. Despite the name juvenile diabetes, type 1 diabetes can be diagnosed at any stage of life, although diagnosis in childhood through young adulthood is most common.

Children who develop type 1 diabetes must eventually take regular insulin injections to keep blood glucose levels under control and do the job of the pancreas. Regular home testing of blood sugar levels is also important to make sure that the treatment is working effectively and to avoid a diabetic emergency such as hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar).

Type 2 Diabetes

The hallmark characteristic of type 2 diabetes is insulin resistance. The pancreas typically produces enough insulin (often too much insulin); however, cells are resistant to the insulin and it may not work as effectively. Type 2 is the most common form of diabetes, and most individuals with the disease are adults. However, children and adolescents can develop type 2 diabetes too, particularly if they are overweight and have a history of type 2 diabetes in their family.

Type 2 diabetes is treated with diet, exercise, and in some cases, oral medication and/or insulin. Self-monitoring of blood glucose levels is also important to assess how well treatment is working.

Demographics

An estimated 18.2 million Americans live with diabetes, and over 5 million of those remain undiagnosed. Up to 95 percent of diabetes patients in the United States have type 2 diabetes; the vast majority of Americans with diabetes are over 20 years of age. Those under 20 represent only 206,000 of the total cases of diabetes in the United States.

While type 2 diabetes is a growing problem among American youth due to climbing obesity rates and more sedentary lifestyles, type 1 diabetes is more prevalent in children and adolescents. An estimated one in 400 to 500 children have type 1 diabetes.

The American Diabetes Association reports that in 2002, diabetes cost Americans an estimated $132 billion in direct medical costs and indirect expenses such as lost productivity and disability payments.

Causes and Symptoms

The causes of diabetes are not completely understood; however, there seem to be both genetic and environmental factors involved in the development of both type 1 and type 2 diabetes, meaning that a person may have a genetic predisposition to developing diabetes, but it takes an environmental factor such as a viral infection or excessive weight gain to actually make the disease surface.

Research has shown that some people who develop diabetes have common genetic markers. In type 1 diabetes, the immune system, the body's defense system against infection, is believed to be triggered by a virus or another microorganism that causes an autoimmune reaction that eventually destroys the insulin-producing cells (i.e., beta cells) in the pancreas. Up to 90 percent of cases of type 1 diabetes are the autoimmune subtype, sometimes called type 1A or immune-mediated diabetes.

The other subtype of type 1 diabetes is called idiopathic, or type 1B diabetes. People who have idiopathic type 1 diabetes also experience beta cell destruction, but it is due to a chromosomal abnormality or an unknown cause rather than any autoimmune process. Only tests for islet cell antibodies and other autoimmune markers can differentiate between the two subtypes, and because testing can be costly and treatment for both is the same (i.e., insulin), a physician may not necessarily order tests for autoimmunity.

Finally, damage caused by diseases of the pancreas (such as pancreatitis), endocrine disorders (e.g., endocrine tumors), and drugs or toxins can also destroy beta cell function.

In type 2 diabetes, family history, age, weight, activity level, and ethnic background can all play a role in the genesis of the disease. Individuals who are at high risk of developing type 2 diabetes mellitus include the following groups:

• people who are overweight or obese (more than 20 percent above their ideal body weight)
• people who have a parent or sibling with type 2 diabetes
• those who belong to a high-risk ethnic population (African-American, Native American, Asian-American, Hispanic, or Pacific Islander)
• people who live a sedentary lifestyle (i.e., exercise less than three times a week)
• women who have been diagnosed with gestational diabetes or have delivered a baby weighing more than 9 lbs (4 kg)
• people with high blood pressure (140/90 mmHg or above)
• people with high density lipoprotein cholesterol (HDL, or "good" cholesterol) level less than or equal to 35 mg/dl and/or a triglyceride level greater than or equal to 250 mg/dl

Several common medications can cause chronic high blood sugar levels and/or promote insulin resistance. These include atypical antipsychotics, beta blockers, corticosteroids, diuretics, estrogens, lithium, protease inhibitors, niacin, and some thyroid preparations.

Both type 1 and type 2 diabetes share similar symptoms caused by chronically high blood glucose levels.

Symptoms of both type 1 and type 2 diabetes include:

• excessive thirst
• frequent urination
• weight loss
• increased appetite
• unexplained fatigue
• slow healing cuts, bruises, and wounds
• frequent or lingering infections (e.g., urinary tract infection)
• mood swings and irritability
• blurred vision
• headache
• high blood pressure
• dry and itchy skin
• tingling, numbness, or burning in hands or feet

Symptoms of diabetes can develop suddenly (over days or weeks) in previously healthy children or adolescents, or can develop gradually, particularly in the case of type 2 diabetes.

Children and adolescents sometimes develop a condition known as diabetic ketoacidosis (DKA) at the time of their diagnosis. Ketones are acid compounds that form in the blood when the body breaks down fats and proteins for energy. When blood sugars are high (i.e., over 249 mg/dl, or 13.8 mmol/L) for prolonged periods of time, ketones build up in the bloodstream to dangerous levels. Symptoms of DKA include abdominal pain, excessive thirst, nausea and vomiting, rapid breathing, extreme lethargy, and drowsiness. Patients with ketoacidosis will also have a fruity or sweet breath odor. Left untreated, this condition can lead to coma and has the potential to be fatal. DKA is more common in people with type 1 diabetes, although it can occur in type 2 diabetes as well.

Symptoms of type 2 diabetes can begin so gradually that a person may not know that he or she has it. It is not unusual for type 2 diabetes to be detected while a patient is seeing a doctor about another health concern that is actually being caused by the yet undiagnosed diabetes, such as heart disease, chronic infections (e.g., urinary tract infections, yeast infections), blurred vision, numbness in the feet and legs, or slow-healing wounds.

When to Call the Doctor

If left untreated, diabetes is a life-threatening condition. Any child displaying symptoms of diabetes should be taken to a doctor or emergency care facility for evaluation immediately.

Diagnosis

Diagnosis of diabetes is suspected based on symptoms and confirmed by blood tests that measure the level of glucose in blood plasma. Dipstick or reagent test strips that measure glucose in the urine can only detect glucose levels above 180 mg/dl and are non-specific, so they are not useful in the diagnosis of diabetes. However, they are a non-invasive way to obtain a fast and simple reading that a physician might use as a basis for ordering further diagnostic blood tests for diabetes, particularly in children.

Blood tests are the gold standard for the diagnosis of both type 1 and type 2 diabetes in children and adults. The American Diabetes Association recommends that a random plasma glucose, fasting plasma glucose, or oral glucose tolerance test (OGTT) be used for diagnosis of diabetes. The OGTT is commonly used as a screening measure for gestational diabetes. Fasting plasma glucose is the test of choice unless a child is exhibiting classic symptoms of diabetes, in which case a random (or casual) plasma glucose test is acceptable.

Unless hyperglycemia is obvious (e.g., blood glucose levels are extremely high or the child experiences DKA), the fasting or random plasma glucose test should be confirmed on a subsequent day with a repeat test.

Fasting Plasma Glucose Test

Blood is drawn from a vein in the child's arm following an eight-hour fast (i.e., no food or drink), usually in the morning before breakfast. The red blood cells are separated from the sample and the amount of glucose is measured in the remaining plasma. A fasting plasma glucose level of 126 mg/dl (7.0 mmol/l) or higher indicates diabetes (with a confirming retest on a subsequent day).

Random Plasma Glucose Test

Blood is drawn at any time of day, regardless of whether the patient has eaten. A random plasma glucose concentration of 200 mg/dl (11.1 mmol/l) or higher in the presence of symptoms indicates diabetes.

Oral Glucose Tolerance Test

Blood samples are taken both before and several times after a patient drinks 75 grams of a glucose-based beverage. If plasma glucose levels taken two hours after the glucose drink is consumed are 200 mg/dl (11.1 mmol/L) or higher, the test is diagnostic of diabetes (and should be confirmed on a subsequent day if possible).

Although the same diagnostic blood tests are used for both types of diabetes, whether a child is diagnosed as type 1 or type 2 can typically be determined based on her personal and medical history. The majority of children diagnosed in childhood are type 1, but if blood test results indicate prediabetes and a child is significantly overweight and has a history of type 2 diabetes in her family, type 2 is a possibility.

Further blood tests can help to differentiate between type 1 and type 2 when the diagnosis is unclear. One of these is an assessment of c-peptide levels, a protein released along with insulin that can help a physician determine whether or not a patient is producing sufficient amounts of insulin. The other is a GAD (Glutamic Acid Decarboxylase) autoantibody test. The presence of GAD autoantibodies may indicate the beginning of the autoimmune process that destroys pancreatic beta cells.

Treatment

Children with type 1 diabetes must take insulin injections or infusions. Their dosage needs may change over time. Sometimes children will experience a decreased need for insulin once blood sugars are brought under control following diagnosis. Their insulin needs may go down, and in some cases, they can stop taking injections for a time. This phenomenon, known as the honeymoon period, can last anywhere from a few days to months.

Children with diabetes and their parents should learn to operate a home blood glucose monitor. Home testing can prevent dangerous highs and lows and help parents and children understand how food and exercise impact blood sugar levels. Blood glucose levels taken before meals are also used to calculate dose size of insulin. A small needle or lancet is used to prick the finger or alternate site and a drop of blood is collected on a test strip that is inserted into a monitor. The monitor then calculates and displays the blood glucose reading on a screen. Although individual blood glucose targets should be determined by a medical professional in light of a child's medical history, the general goal is to keep them as close to normal (i.e., 90 to 130 mg/dl or 5 to 7.2 mmol/L before meals) as possible.

Insulin

Children with type 1 diabetes need daily injections of insulin to help their bodies use glucose. The amount and type of insulin required depends on the height, weight, age, food intake, and activity level of the individual diabetic patient. Some patients with type 2 diabetes may also need to use insulin injections if their diabetes cannot be controlled with diet, exercise, and oral medication. Injections are given subcutaneously, that is, just under the skin, using a small needle and syringe, an insulin pen injector, an insulin infusion pump, or a jet injector device. Injection sites can be anywhere on the body where there is a layer of fat available, including the upper arm, abdomen, or upper thigh.

Insulin may be given as an injection of a single dose of one type of insulin once a day, or different types of insulin can be mixed and given in one dose or split into two or more doses during a day. Patients who require multiple injections over the course of a day may be able to use an insulin pump that administers small doses of insulin on demand. The small battery-operated pump is worn outside the body and is connected to a cannula (a thin, flexible plastic tube) that is inserted into the abdomen called an insertion set. Pumps are programmed to infuse a small, steady infusion of insulin (called a basal dose) throughout the day, and larger doses (called boluses) before meals. Because of the basal infusion, pumps can offer many children much tighter control over their blood glucose levels and more flexibility with their diet than insulin shots afford them.

Regular insulin is fast-acting and starts to work within 15 to 30 minutes, with its peak glucose-lowering effect about two hours after it is injected. Its effects last for about four to six hours. NPH (neutral protamine Hagedorn) and Lente insulin are intermediate-acting, starting to work within one to three hours and lasting up to 18 to 26 hours. Ultra-lente is a long-acting form of insulin that starts to work within four to eight hours and lasts 28 to 36 hours. Peakless, or basal-action insulin (insulin glargine, or Lantus) starts working in 15 minutes and has a duration of between 18 and 26 hours.

Nutritional Concerns

Because dietary carbohydrates are the primary source of glucose for the body (the other source being the liver), it is very important that children with diabetes learn to read labels and be aware of the amount of carbohydrates in the foods they eat. Children and their parents are usually advised to consult a registered dietitian (RD) to create an individualized, easy to manage food plan that fits their family's health and lifestyle needs. A well-balanced, nutritious diet provides approximately 50 to 60 percent of calories from carbohydrates, approximately 10 to 20 percent of calories from protein, and less than 30 percent of calories from fat. The number of calories required depends on age, weight, and activity level. An RD can also teach the family how to use either the dietary exchange lists or carbohydrate counting system to monitor food intake.

Each food exchange contains a known amount of calories in the form of protein, fat, or carbohydrate. A patient's diet plan will consist of a certain number of exchanges from each food category (meat or protein, fruits, breads and starches, vegetables, and fats) to be eaten at meal times and as snacks. Patients have flexibility in choosing which foods they eat as long as they stick with the number of exchanges prescribed by their RD based on their caloric requirements.

Carbohydrate counting involves totaling the grams of carbohydrates in the foods your child eats to ensure the child does not exceed her goal for the day. In the simple-carb counting method, one carbohydrate choice or unit equals 15 grams of carbohydrates (which is equivalent to one starch or fruit exchange in the exchange method). The number of carb choices allowed daily is based on caloric requirements.

Children with type 1 diabetes who use fast-acting insulin before meals may find that carb counting gives them tighter control of their blood glucose levels, since they can compute the number of insulin units based on both their carbohydrate intake (called the carbohydrate to insulin ratio) and before-meal blood glucose readings.

Dietary changes and moderate exercise are usually the first treatments implemented in type 2 diabetes. Weight loss may be an important goal in helping overweight children and adolescents control their blood sugar levels. Exercise helps keep blood glucose levels down and has other health benefits, as well.

Oral Medications

Children with type 2 diabetes may be prescribed oral medications if they are unable to keep their blood glucose levels under control with dietary and exercise measures. As of 2004, metformin was the only oral medication approved by the U.S. FDA for use in children over age ten. Metformin (trade name Glucophage) is in the biguanide class of drugs and works by reducing the amount of glucose the liver produces and the amount of circulating insulin in the body. Other adult type 2 diabetes medications, such as sulfonylureas and meglitinide drugs, which work by increasing insulin production, may be prescribed off-label for pediatric use.

Transplants

Transplantation of a healthy pancreas into a patient with type 1 diabetes can eliminate the need for insulin injections; however, this transplant is typically done only if a kidney transplant is performed at the same time. Although a pancreas transplant is possible, it is not clear if the potential benefits outweigh the risks of the surgery and life-long drug therapy needed to prevent organ rejection, particularly in the case of children.

A second type of transplant procedure, as of 2004 in experimental clinical trials and not available to children, is an islet cell transplant. In this type of treatment, insulin-producing islet cells are harvested from a donor pancreas and injected into the liver of a recipient, where they attach to new blood vessels and (ideally) begin producing insulin. A lifetime regimen of immunosuppressive drugs is required to prevent rejection of the transplanted cells.

Prognosis

As of 2004 diabetes is a chronic and incurable disease. While stem cell research holds great promise for future therapies and potential cures, as of the early 2000s the best hope for keeping children well with diabetes and avoiding long-term complications is maintaining good blood glucose control. The landmark Diabetes Control and Complications Trial (DCCT) found that patients with type 1 diabetes who kept their blood sugar levels as close to normal as possible reduced their risk for developing diabetic eye disease by 76 percent, for diabetic kidney disease by 50 percent, and for diabetic neuropathy by 60 percent.

Diabetes and its related complications was the sixth leading cause of death in 2000. According to the National Institutes of Health, cardiovascular, or heart and blood vessel disease, is the leading cause of diabetes-related death. Uncontrolled diabetes is a leading cause of blindness, end-stage renal disease, and limb amputations. Eye problems including cataracts, glaucoma, and diabetic retinopathy also are more common in people with diabetes.

Diabetic neuropathy is the result of nerve damage caused by uncontrolled diabetes. Autonomic neuropathy affects the autonomic nervous system and can cause gastroparesis (nerve damage of the stomach), neurogenic bladder (nerve damage of the urinary bladder), and a host of other problems with involuntary functions of the nervous system.

In peripheral neuropathy (PN), nerve damage in the extremities (e.g., the legs and feet) causes numbness, pain, and burning. Diabetic foot ulcers are a particular problem since frequently the patient does not feel the pain of a blister, callous, or other minor injury. Poor blood circulation in the legs and feet contribute to delayed wound healing. The inability to sense pain along with the complications of delayed wound healing can result in minor injuries, blisters, or calluses becoming infected and difficult to treat. The most serious consequence of this condition is the potential for amputation of toes, feet, or legs due to severe infection.

Diabetic kidney disease is another common complications of diabetes. Long-term complications may include the need for kidney dialysis or a kidney transplant due to kidney failure. Diabetes is the number one cause of chronic kidney failure in America.

Children and adults with the autoimmune form of type 1 diabetes are also at greater risk for other autoimmune disorders, including thyroid disease, celiac sprue (sometimes called gluten intolerance), autoimmune hepatitis, myasthenia gravis, and pernicious anemia.

Prevention

As of 2004 research continues on diabetes prevention and improved detection of those at risk for developing diabetes. While the onset of type 1 diabetes is unpredictable, the risk of developing type 2 diabetes may be reduced by maintaining ideal weight and exercising regularly. Both physical and emotional stress can cause increases in blood glucose levels, so getting regular immunizations and well-child check-ups, practicing good sleep and hygiene habits, encouraging emotional and social growth, and maintaining a stress-controlled lifestyle is important for children with type 1 or type 2 diabetes.

Parental Concerns

Parents of children with diabetes must work with their child's teachers and school administrators to ensure that their child is able to test her blood sugars regularly, take insulin as needed, and have access to food or drink to treat a low. Someone at school should also be trained in how to administer a glucagon injection, an emergency treatment for a hypoglycemic episode when a child loses consciousness.

Section 504 of the Rehabilitation Act of 1973 enables parents to develop both a Section 504 plan (which describes a child's medical needs) and an individualized education plan (IEP) (which describes what special accommodations a child requires to address those needs). An IEP should cover such issues as blood glucose monitoring, dietary plans, and treating highs and lows. If school staff has little to no experience with diabetes, bringing in a certified diabetes educator (CDE) to offer basic training may be useful.

Children with diabetes can lead an active life and enjoy most of the activities and foods their peers do, with a few precautions to avoid blood sugar highs or lows. A certified diabetes educator that has experience working with children can help them understand the importance of regular testing as well as methods for minimizing discomfort. Diabetes summer camps, where children can learn about diabetes care in the company of peers and counselors who also live with the disease, may be useful from both a health and a social standpoint. In addition, peer support groups can sometimes help children come to terms with their diabetes.

Hypoglycemia, or low blood sugar, can be caused by too much insulin, too little food (or eating too late to coincide with the action of the insulin), alcohol consumption, or increased exercise. A child with symptoms of hypoglycemia may be hungry, cranky, confused, and tired. The patient may become sweaty and shaky. Left untreated, a child can lose consciousness or have a seizure. This condition is sometimes called an insulin reaction and should be treated by giving the patient something sweet to eat or drink like candy, juice, glucose gel, or another high sugar snack. A child who loses consciousness due to a low should never be given food or drink due to the risk of choking. In these cases, a glucagon injection should be administered and the child should be taken to the nearest emergency care facility.

While exercise can lower blood glucose levels, children with diabetes can and do excel in sports. Proper hydration, frequent testing, and a before-game or practice snack can prevent hypoglycemia. Coaches or another onsite adult should be aware of a child's medical condition and be prepared to treat a hypoglycemic attack if necessary.

The other potential danger to a child with diabetes—diabetic ketoacidosis—is uncommon and most likely to occur prior to a diagnosis. It may also happen if insulin is discontinued or if the body is under stress due to illness or injury. Ketones in the urine can be detected using dipstick tests (e.g., Ketostix), or detected using a home ketone blood monitor. Early detection facilitates early treatment and can prevent full-blown DKA.

Because the symptoms of DKA can mimic the flu, and the flu can increase blood sugar levels, a child who comes down with a flu-like illness should be monitored closely and tested regularly. An increase in insulin may also be necessary; parents of children with diabetes should talk with their pediatrician about a sick day plan for their child before they need it.

See also Hypoglycemia.

Resources

Books

The American Diabetes Association Complete Guide to Diabetes, 3rd ed. Alexandria, VA: American Diabetes Association, 2002.

Brackenridge, Betty, and Richard Rubin. Sweet Kids: How to Balance Diabetes Control and Good Nutrition with Family Peace, 2nd ed. Alexandria, VA: American Diabetes Association, 2002.

Ford-Martin, Paula, with Ian Blumer. The Everything Diabetes Book. Avon, MA: Adams Media, 2004.

Organizations

American Diabetes Association. 1701 North Beauregard St., Alexandria, VA 22311. Web site: www.diabetes.org.

American Dietetic Association. 216 W. Jackson Blvd., Chicago, IL 60606–6995. Web site: www.eatright.org.

Children with Diabetes. 5689 Chancery Place, Hamilton, OH 45011. Web site: www.childrenwithdiabetes.org.

Juvenile Diabetes Research Foundation. 120 Wall St., 19th Floor, New York, NY 10005. Web site: www.jdrf.org.

National Diabetes Information Clearinghouse. 1 Information Way, Bethesda, MD 20892–3560. Web site: www.niddk.nih.gov/health/diabetes/ndic.htm.

Web Sites

"2004 Clinical Practice Recommendations." Diabetes Care, January, 2004. Available online at (accessed December 26, 2004).

Ford-Martin, Paula. "About Diabetes" Available online at (accessed December 26, 2004).

Mendosa, David. David Mendosa's Diabetes Directory. Available online at www.mendosa.com/diabetes.htm (accessed December 26, 2004).

[Article by: Paula Ford-Martin Altha Roberts Edgren Teresa G. Odle]

The term "diabetes mellitus" represents a group of conditions characterized by abnormally high blood glucose levels (hyperglycemia). In 1997, nearly 16 million people in the United States had diabetes; approximately 10.3 million were diagnosed with the conditions, while an estimated 5.4 million were undiagnosed. Diabetes may be complicated by uncontrolled hyperglycemia, and treated diabetes may be complicated by abnormally low blood glucose levels (hypoglycemia). Maternal diabetes is associated with an increased incidence of major birth defects. Over time, diabetes may cause complications involving the eyes (retinopathy), kidneys (nephropathy), and nerves (neuropathy). Diabetes is also associated with an increased incidence of cardiovascular disease, including stroke, heart attack, and peripheral vascular disease. In the United States today, diabetes is a leading cause of birth defects, blindness, kidney failure, and nontraumatic leg amputations. It is also a major contributor to cardiovascular disease. Diabetes is the seventh leading cause of death in the United States, and medical care for people with diabetes is estimated to cost over $100 billion per year.

When diabetes is associated with marked hyperglycemia, it produces characteristic symptoms and signs; particularly increased thirst (polydipsia), increased urination (polyuria), and unexplained weight loss. At other times, hyperglycemia sufficient to cause changes in the eyes, kidneys, and nerves, and to increase the risk of cardiovascular disease, may be present without clinical symptoms. During this asymptomatic period, an abnormality in glucose metabolism may be demonstrated by measuring fasting venous glucose or venous glucose after an oral glucose challenge.

Diagnosis

When a patient is symptomatic and the plasma glucose is unequivocally elevated, a diagnosis of diabetes presents no difficulty. When a patient is without clinical symptoms, a diagnosis of diabetes is more difficult. According to a 1997 American Diabetes Association (ADA) report, there are three ways to diagnose diabetes (see Table 1). All require measurement of venous plasma glucose, and each must be confirmed on a subsequent day by any one of the three methods. In general, the oral glucose tolerance test is not recommended for routine clinical use and is performed only in patients with elevated but nondiagnostic fasting plasma-glucose levels with a high index of suspicion for diabetes.

Classification

Once a diagnosis of diabetes mellitus is established, it is necessary to differentiate the various forms of the syndrome. Prior to 1979, diabetes was

Table 1

classified on the basis of age at diagnosis as either juvenile-onset diabetes mellitus (JODM) or adult-onset diabetes mellitus (AODM). In the late 1970s and early 1980s, a new classification system recognized two major forms of diabetes: insulin-dependent diabetes mellitus (IDDM or type I diabetes) and non-insulin-dependent diabetes mellitus (NIDDM or type II diabetes). In 1997, the American Diabetes Association recommended modifications to this classification system that eliminated the terms "insulin-dependent diabetes mellitus" and "non-insulin-dependent diabetes mellitus" and their acronyms. The terms "type 1" and "type 2" were retained, with Arabic numerals replacing the Roman numerals. Other specific types of diabetes were also recognized.

Type 1 diabetes is caused by pancreatic beta cell (B-cell) destruction. Immune-mediated type 1 diabetes results from cell-mediated autoimmune destruction of the B-cells of the pancreatic islets. This type of diabetes also has strong genetic or human leukocyte antigen (HLA) associations that can be either predisposing or protective. Another form of type 1 diabetes, termed "idiopathic" type 1 diabetes, is strongly inherited but lacks immunologic evidence for B-cell autoimmunity and is not HLA-associated. Most patients with

Table 2

idiopathic type 1 diabetes are of African or Asian descent.

Type 1 diabetes accounts for approximately 5 percent of diagnosed diabetes in the United States—approximately 500,000 Americans have type 1 diabetes. Type 1 diabetes commonly occurs in childhood and adolescence, but it can occur at any age. Patients with type 1 diabetes are prone to ketoacidosis (decompensated diabetes with hyperglycemia and presence of abnormal acids [ketones] in the blood). Many affected patients have no family history of diabetes. Although most patients with type 1 diabetes are lean when they are diagnosed, the presence of obesity is not incompatible with the diagnosis.

Type 2 diabetes is characterized by both impairment of insulin secretion and defects in insulin action. It is often unclear which abnormality is the primary cause of hyperglycemia. Although patients with this type of diabetes may have insulin levels that appear normal or elevated, insulin levels are always low relative to the elevated plasma glucose levels. Thus, insulin secretion is defective in these patients and insufficient to compensate for the degree of insulin resistance. Although the specific origin of type 2 diabetes is not known, autoimmune destruction of B-cells does not occur. Although type 2 diabetes is associated with a strong genetic predisposition, the genetics of this form of diabetes are complex and not clearly defined.

Type 2 diabetes accounts for approximately 95 percent of diagnosed diabetes in the United States (9.8 million cases), and for the vast majority of the cases of undiagnosed diabetes. The risk of type 2 diabetes increases with age, obesity, and physical inactivity. As such, it is often regarded as a disease associated with a modern Western lifestyle. Type 2 diabetes occurs more frequently in women with prior gestational diabetes and in individuals with hypertension and dyslipidemia. Affected patients often have a family history of diabetes. Type 2 diabetes is more common in African Americans, Hispanic Americans, and Native Americans than in non-Hispanic white Americans. Ketoacidosis seldom occurs spontaneously in type 2 diabetes, but it may arise in association with the stress of another illness. Approximately 70 percent of patients with type 2 diabetes are obese.

Treatment

Large, prospective, randomized, controlled clinical trials in both type 1 and type 2 diabetes have demonstrated that normal or near-normal blood glucose control can delay or prevent the development of major birth defects and the development and progression of complications affecting the eyes, kidneys, and nerves. Accordingly, the goals for management for both type 1 and type 2 diabetes are to achieve glucose levels as close to the nondiabetic range as possible while minimizing the side-effects of treatment (hypoglycemia and weight gain).

In nondiabetic subjects, blood glucose levels are between 70 and 90 mg/dl (milligrams per deciliter) in the fasting state and rise to 120 to 140 mg/dl one to two hours after meals. These values reflect normal glucose tolerance. Average glucose levels may be assessed by measurement of glycosylated hemoglobin (hemoglobin A1c), is a measure of the average blood glucose level over the previous two to four months. In nondiabetic subjects, hemoglobin A1c is generally less than 6.1 percent, and in poorly controlled diabetic subjects, it may rise to 12 percent or higher.

In general, the goals of treatment are to achieve blood glucose and hemoglobin A1c levels as close to the nondiabetic range as possible with diet, physical activity, and medications.

Diet. In type 1 diabetes, diet is designed to provide adequate nutrients for growth and development and for the maintenance of ideal body weight. The recommended diet includes approximately 20 percent of daily calories from protein, 30 percent from fat, and 50 percent from complex carbohydrates. Simple sugars are limited to prevent excessive glucose excursions, and carbohydrate content is distributed into regular meals and

Table 3

snacks so that a similar quantity of carbohydrate is consumed at approximately the same time each day.

In type 2 diabetes, caloric content is adjusted to achieve and maintain an ideal body weight or, in those who are obese, to produce gradual weight loss or at least weight maintenance. Dietary composition may also be adjusted in light of intercurrent conditions. For example, sodium may be restricted for patients with hypertension, and both total fat and saturated fat may be restricted for those with high cholesterol.

Exercise. Exercise lowers blood glucose and improves glucose tolerance in diabetics. Other benefits of exercise are reductions in LDL cholesterol and triglycerides levels, and improvements in HDL cholesterol, improvements in blood pressure, improved cardiovascular fitness, and an increased sense of well-being and quality of life. Because exercise may potentiate the hypoglycemic effect of injected insulin and may, paradoxically, result in elevated blood glucose levels and the rapid development of ketosis in type 1 diabetic patients in poor metabolic control, the goal of management in type 1 diabetes is to permit people to enjoy and participate safely in physical and sport activities. In type 2 diabetes, exercise is frequently prescribed as an adjunct to reduced-calorie diets for weight reduction and to improve insulin resistance.

Medications. Because patients with type 1 diabetes are absolutely insulin deficient, treatment requires insulin injections. Although one or two injections per day are often adequate to prevent symptoms of hyperglycemia, intensive therapy employing three or four insulin injections per day, or continuous subcutaneous insulin infusion, may be necessary to achieve near-normal glucose control.

Both oral medications and injected insulin are used for the treatment of type 2 diabetes. Four groups of oral agents are currently available: insulin secretagogues, which enhance nutrient-stimulated insulin secretion; the biguanides, which suppress abnormal glucose production by the liver; the thiazolidinediones, which reduce insulin resistance at the level of muscle and fat; and the alpha-glucosidase inhibitors, which slow the breakdown and absorption of carbohydrates and reduce postprandial glucose excursions. To the extent that these four groups of oral medications have different mechanisms of action, they can be used clinically in combination. When oral agents are ineffective in controlling hyperglycemia or achieving glycemic goals, insulin is added or substituted.

Monitoring

Self-monitoring of blood glucose is integral to modern diabetes therapy. A lancet is used to obtain a small drop of blood, which is placed on a reagent strip and inserted in a small battery-powered meter. The meter reports the blood glucose level in less than a minute. Results of self-monitoring of blood glucose are used to guide adjustments in diet, exercise, and medications, for the monitoring and treatment of hypoglycemia, and in the home management of intercurrent illness.

Incidence and Prevalence

The number of people developing diabetes and the number of people with diabetes are increasing worldwide. In 2000, it was estimated that 154 million persons, or 4.2 percent of the world's population, twenty years of age and older had diabetes. By the year 2025, it is estimated that nearly 300 million persons, or 5.4 percent of the world's population, twenty years of age and older will have diabetes. The major part of this increase will occur in developing countries due to the aging of the population and increasing urbanization (associated with increased body weight and decreased physical activity).

In 1994, there were 939,000 Americans newly diagnosed with diabetes, with a disproportionate number among the elderly and minority populations. The incidence of diagnosed diabetes was3.61 cases per 1,000 persons per year in 1994 (see Table 2).

In 1994, about 8 million persons in the United States (3.1 percent of the population) reported that they had diabetes. The prevalence of diagnosed diabetes increases with age (see Table 3).

Mortality

Diabetes is the seventh leading cause of deaths in the United States. The highest death rates due to diabetes are observed in older Americans and in minority populations. Death certificates underestimate diabetes mortality because of underreporting of diabetes. Only about 10 percent of people with diabetes who die have diabetes listed as the underlying cause of death on their death certificates, and only about 40 percent have it listed anywhere on their death certificates. Diabetes was the underlying cause of death for approximately 57,000 Americans in 1994, and diabetes was recorded on the death certificate of approximately 182,000 Americans. In 1994, black women had the highest death rates due to diabetes, followed by white women and men. That same year, 44 percent of all diabetes-related deaths (80,000 deaths) had cardiovascular disease listed as the underlying cause. Of these deaths, approximately 60 percent were caused by ischemic heart disease and 15 percent by stroke.

Complications and Comorbidities Associated With Diabetes

Diabetic Ketoacidosis (DKA). Ketoacidosis is an acute metabolic complication of diabetes associated with hyperglycemia, nausea, vomiting, abdominal pain, dehydration, ketonemia, and acidosis. In 1994, DKA was the primary diagnosis for 89,000 hospital discharges and a listed diagnosis for 113,000 hospital discharges. Clinical trials have demonstrated that improved education in self-management and improved access to care can prevent up to 70 percent of DKA hospitalizations.

Adverse Outcomes of Pregnancy. Each year in the United States, type 1 diabetes complicates approximately 7,000 pregnancies and type 2 diabetes complicates approximately 12,000 pregnancies. Up to 1,700 infants (9%) of mothers with pregnancies complicated by diabetes (in the U.S.) are born with birth defects affecting the brain, spinal cord, heart, kidneys, and skeleton. Clinical trials have demonstrated that with intensive glycemic control before conception and during the first trimester, the incidence of major birth defects may be reduced to 2 percent, the rate that occurs in infants of nondiabetic mothers.

Diabetic Eye Disease. Diabetes is the leading cause of new cases of legal blindness in Americans between twenty and seventy-four years of age. As many as 40,000 Americans become blind each year as a result of diabetes. In type 1 diabetes, most legal blindness is due at least in part to diabetic retinopathy. Timely diagnosis and appropriate laser treatment can prevent up to 90 percent of blindness due to diabetic retinopathy. In type 2 diabetes, cataract, glaucoma, and senile macular degeneration are more frequent causes of blindness.

Diabetic Kidney Disease. Diabetic nephropathy is characterized by hypertension, proteinuria, and progressive renal insufficiency. Diabetes is now the leading cause of end-stage renal disease (kidney failure requiring dialysis or kidney transplant for survival). In 1997, over 33,000 Americans developed end-stage renal disease due to diabetes. Early detection, aggressive blood pressure control, and treatment with angiotensin-converting enzyme inhibitors can reduce the progression of diabetic nephropathy by about 60 percent.

Amputations. Diabetic neuropathy, peripheral vascular disease, and infection predispose people with diabetes to gangrene and amputations. More than half of all nontraumatic lower extremity amputations (LEAs) occur in people with diabetes. In 1994, there were approximately 67,000 diabetes-related hospital discharges with LEA reported as a procedure in the United States. Clinical trials have demonstrated that early detection of insensitive and deformed feet and multidisciplinary foot-care programs can reduce the rate of amputation by more than 50 percent.

Cardiovascular Disease Cardiovascular disease (CVD) is the leading cause of morbidity and

Table 4

mortality in people with diabetes. Stroke, heart attack, and peripheral vascular disease are two to four times more common in people with diabetes than in people without diabetes. In 1994, there were 1,144,000 diabetes-related hospital discharges that had CVD listed as the primary discharge diagnosis (see Table 4). Part of the increased incidence of cardiovascular disease in people with diabetes is due to the greater prevalence of cardiovascular risk factors, including hypertension, dyslipidemia, and cigarette smoking. Clinical trials have demonstrated that pharmacologic treatments for hypertension and dyslipidemia are as effective, if not more effective, in people with diabetes compared to people without diabetes.

Costs of Diabetes

Health care costs incurred by people with diabetes include non-diabetes-related and diabetes-related costs. In the United States, in 1992, the direct cost of non-diabetes-related and diabetes-related medical care incurred by people with diabetes was estimated to be $105.2 billion. The direct cost of medical care attributable to diabetes was estimated to be $45.2 billion and the indirect cost of diabetes was estimated to be $46.6 million (see Table 5).

In 1992, per capita health care expenditures for people with diabetes averaged $9,493, compared to $2,604 for people without diabetes. When adjusted for age, per capita health care expenditures for people with diabetes were approximately

Table 5

$3,800 higher for people with diabetes than for people without diabetes ($6,425 versus $2,604).

The fact that 62 percent of direct health care costs among people with diabetes and 82 percent of costs directly attributable to diabetes are incurred in the hospital setting suggests that the majority of costs are associated with the treatment of the late, chronic complications of diabetes.

Screening for Type 2 Diabetes

One-third of diabetes in the United States is undiagnosed, and one-third to one-half of all diabetes worldwide is undiagnosed. This finding, combined with the fact that glycemic management can prevent or delay the development of complications, and the fact that diabetic patients may already have complications at clinical diagnosis, have lead some to call for public health screening for type 2 diabetes. In general, screening is appropriate in asymptomatic populations when six specific conditions are met (see Table 6).

Table 6

Diabetes imposes substantial morbidity and mortality on the population. The natural history of type 2 diabetes is well understood, and with systematic testing, diabetes can be diagnosed in asymptomatic, preclinical, subjects. Unfortunately, although it is clear that intensified management can improve outcomes, no studies have demonstrated the effectiveness or safety of early treatment. Likewise, there is no consensus as to the optimal approach to screening for type 2 diabetes. Ideally, a screening test should be both sensitive and specific. Generally, however, trade-offs must be made between sensitivity and specificity (increasing sensitivity reduces specificity, and increasing specificity reduces sensitivity). In some health systems, the costs of screening and treatment are reasonable, but in others they are simply unaffordable. Finally, although it is recognized that screening must be an ongoing process, no empirical data exist to indicate the optimal screening frequency.

Questionnaires that use self-reported demographic, behavioral, and past medical history to assign a person to a higher or lower risk group; fasting, random, and postprandial urine glucose tests; fasting, random, and postprandial capillary whole blood and capillary plasma glucose tests; fasting, random, and postprandial venous whole blood and plasma glucose tests; and hemoglobin A1c have all been evaluated as screening tests for diabetes. In general, questionnaires perform rather poorly as screening tests for diabetes. Measurement of glycosuria using a cut-off point greater than or equal to a trace value generally has a low sensitivity and a high specificity. Capillary or venous whole blood or plasma glucose determinations have generally performed better than urine glucose testing. With both urine and blood testing, random, postprandial, and glucose-loaded tests perform better than fasting tests. There is little consensus, however, as to optimal cut-points for defining positive tests. Screening with hemoglobin A1c has suffered from lack of standardization of the assay. Even as this problem has been addressed, the test has generally been found to be specific but less sensitive than glucose measurements.

Accordingly, the American Diabetes Association has recommended that clinicians should be vigilant and recognize clinical histories and signs suggestive of diabetes that warrant testing. Generally, screening of high-risk individuals for type 2 diabetes should be performed only as part of ongoing medical care, understanding that the evidence is incomplete and questions remain as to the benefits and risks of early treatment, the optimal screening methods and cut-points, and screening frequency. Community-based screening for diabetes is generally associated with a low yield and poor follow-up, and it probably does not represent a good use of resources.

(SEE ALSO: Cardiovascular Diseases; Glycosylated Hemoglobin; Noncommunicable Disease Control; Nutrition; Screening)

Bibliography

Centers for Disease Control and Prevention (1997). Diabetes Surveillance, 1997. Atlanta, GA: CDC.

DCCT Research Group (1993). "The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus." New England Journal of Medicine 329: 977–986.

Engelgau, M. M.; Venkat Narayan, K. M.; and Herman, W. H. (2000). "Screening for Type 2 Diabetes." Diabetes Care 23:1563–1580.

Fox-Ray, N.; Mills, S.; and Thamer, M. (1993). Direct and Indirect Costs of Diabetes in the United States in 1992. Alexandria, VA: American Diabetes Association.

King, H.; Aubert, R. E.; and Herman, W. H. (1998). "Global Burden of Diabetes, 1995–2025: Prevalence, Numerical Estimates, and Projections." Diabetes Care 21:1414–1431.

Lebovitz, H. E., ed. (1998) Therapy for Diabetes Mellitus and Related Disorders, 3rd edition. Alexandria, VA: American Diabetes Association.

National Diabetes Data Group (1995). Diabetes in America, 2nd edition. Bethesda, MD: National Institute of Health.

Rubin, R. J.; Altman, W. M.; and Mendelson, D. N. (1994). "Health Care Expenditures for People with Diabetes Mellitus, 1992." Journal of Clinical Endocrinolical Metabolism 78:809a–809f.

UK Prospective Diabetes Study (UKPDS) Group (1998). "Intensive Blood-Glucose Control with Sulphonylureas or Insulin Compared with Conventional Treatment and Risk of Complications in Patients with Type 2 Diabetes." Lancet 352:857–853. (Published erratum appears in Lancet 354:602.

— WILLIAM H. HERMAN; LIZA L. ILAG

For more information on diabetes mellitus, visit Britannica.com.

A disorder of carbohydrate metabolism characterized by an increased blood glucose level (hyperglycaemia) and the presence of glucose in the urine (glycosuria). There are two main types of diabetes mellitus: Type I diabetes (also known as juvenile-onset diabetes and insulin-dependent diabetes) generally has a sudden onset in young people who develop almost total insulin deficiency that usually requires daily insulin injections; Type II diabetes (also known as adult-onset diabetes and non-insulin-dependent diabetes) usually develops gradually in adulthood and is caused by delayed or impaired insulin secretion, impaired insulin action (see insulin resistance), or excessive glucose output by the liver. Exercise is often an important part of the management of diabetes. It can be effective in modifying the course of the disease, helping to reduce the risk of vascular complications (e.g. coronary artery disease). Regular aerobic exercise might also reduce the risk of developing Type II diabetes and it improves the control of food glucose levels in those who already have the disease. However, it is important that the diabetic, coach, and friends are well acquainted with potential problems during exercise, such as hypoglycaemia. A glucose drink or some other simple and quick source of glucose should be available if needed to prevent insulin shock. Physical activity reduces the concentration of insulin in the blood, and acute bouts of exercise increases the sensitivity of target cells to insulin, reducing the dosages required by a diabetic. Diabetics often suffer complications such as peripheral neuropathy which can reduce sensation in the feet and peripheral vascular disease, which may impair blood circulation in the feet. They therefore need to pay particular attention to their feet, taking care to select proper footwear, especially if they perform weight-bearing exercises (e.g. road running). The American Academy of Pediatrics, Committee on Sports Medicine states that diabetics can participate in all sports with proper attention to blood glucose concentration, hydration, and insulin therapy. The Committee advises that blood glucose concentration should be monitored every 30 min during continuous exercise and 15 min after completion of exercise.

A chronic disease in which carbohydrates cannot be metabolized properly (see metabolism) because the pancreas fails to secrete an adequate amount of insulin. Without enough insulin, carbohydrate metabolism is upset, and levels of sugar in the blood rise.

A broadly applied term used to denote a complex group of syndromes that have in common a disturbance in the oxidation and utilization of glucose, which is secondary to a malfunction of the beta cells of the pancreas, whose function is the production and release of insulin. Because insulin is involved in the metabolism of carbohydrates, proteins and fats, diabetes is not limited to a disturbance of glucose homeostasis alone.
Diabetes mellitus has been recorded in all species but is most commonly seen in middle-aged to older, obese, female dogs. A familial predisposition has been suggested. It is possible to identify two types of diabetes, corresponding to the disease in humans, depending on the response to an intravenous glucose tolerance test. Type I is insulin-dependent and comparable to the juvenile onset form of the disease in children in which there is an absolute deficiency of insulin—there is a very low initial blood insulin level and a low response to the injected glucose. This form is seen in a number of dog breeds, particularly the Keeshond, Doberman pinscher, German shepherd dog, Poodle, Golden retriever and Labrador retriever.
Type II is non-insulin-dependent, similar to the adult onset diabetes in humans due to pancreatic damage—there is a high or normal initial blood insulin level and no increase in insulin levels as a result of the glucose load. It is the form seen most often in cats.

• brittle d. m. — diabetes mellitus that is difficult to control, characterized by unexplained oscillation between hypoglycemia and diabetic ketoacidosis.
• gestational d. m. — diabetes mellitus in which onset or recognition of impaired glucose tolerance occurs during pregnancy.
• hyperosmolar d. m. — a syndrome of marked hyperglycemia and hyperosmolarity with central nervous signs, resembling diabetic coma.
• insulin-dependent d. m. (IDDM) — due to deficient secretion of insulin by the beta cells of the pancreas. See diabetes mellitus type I (above).
• juvenile d. m. — develops in the young; see diabetes mellitus type I (above).
• non-insulin-dependent d. m. (NIDDM) — the secretion of insulin is unimpaired but the response of tissue receptors is diminished. See diabetes mellitus type II (above).
• secondary d. m. — hyperglycemia may occur in association with pancreatitis, hyperadrenocorticism, acromegaly, and treatment with glucocorticoids or progesterone.
• steroid d. m. — altered carbohydrate tolerance is induced by glucocorticoids and progestogens. Hyperglycemia and diabetes mellitus can be associated with the administration of such drugs or hyperadrenocorticism.

For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. For diabetes mellitus in pets, see diabetes in cats and dogs.

Diabetes mellitus
Classification and external resources
Universal blue circle symbol for diabetes.[1]
ICD-10	Ee10.htm+ e10 10 . – Ee10.htm+ e14 14 .
ICD-9	250
MedlinePlus	001214
MeSH	C18.452.394.750

Diabetes mellitus (pronounced /ˌdaɪ.əˈbiːtiːz/ or /ˌdaɪ.əˈbiːtɨs/; /mɨˈlaɪtəs/ or /ˈmɛlɨtəs/)—often referred to simply as diabetes—is a disease in which the body does not produce or properly use insulin. Insulin is a hormone produced in the pancreas, an organ near the stomach. Insulin is needed to turn sugar and other food into energy. When one has diabetes, the body either doesn’t make enough insulin or can’t use its own insulin as well as it should, or both. This causes sugars to build up too high in the blood.^[2]

The cause of diabetes continues to be a mystery, although both genetics and environmental factors such as obesity and lack of exercise appear to play roles.^[3] The American Diabetes Association reported in 2009 that there are 23.6 million children and adults in the United States—7.8% of the population, who have diabetes. While an estimated 17.9 million in the US alone have been diagnosed with diabetes, nearly one in four (5.7 million) diabetics are unaware that they have the disease.^[3]

Four related classifications of diabetes have been identified:^[3]

• Type 1: Results from the body's failure to produce insulin. It is estimated that 5-10% of Americans who are diagnosed with diabetes have type 1 diabetes. Presently almost all persons with type 1 diabetes must take insulin injections.
• Type 2: Results from a condition in which the body fails to use insulin properly, combined with relative insulin deficiency. Most Americans who are diagnosed with diabetes have type 2 diabetes.
• Gestational diabetes. Pregnant women who have never had diabetes before but who have high blood sugar (glucose) levels during pregnancy are said to have gestational diabetes. Gestational diabetes affects about 4% of all pregnant women and is usually of type 2.
• Pre-diabetes. Termed "America's largest healthcare epidemic,"^[4]:10-11pre-diabetes is a condition that occurs when a person's blood glucose levels are higher than normal but not high enough for a diagnosis of type 2 diabetes. As of 2009 there are 57 million Americans who have pre-diabetes, in addition to the 23.6 million with diabetes.^[3]

All forms of diabetes have been treatable since insulin became medically available in 1921, but there is no cure.

Diabetes and its treatments can cause many complications. Acute complications including hypoglycemia, ketoacidosis, or nonketotic hyperosmolar coma may occur if the disease is not adequately controlled. Serious long-term complications include cardiovascular disease, chronic renal failure, retinal damage, which can lead to blindness, several types of nerve damage, and microvascular damage, which may cause erectile dysfunction and poor wound healing. Poor healing of wounds, particularly of the feet, can lead to gangrene, and possibly to amputation. Adequate treatment of diabetes, as well as increased emphasis on blood pressure control and lifestyle factors such as not smoking and maintaining a healthy body weight, may improve the risk profile of most of the chronic complications. In the developed world, diabetes is the most significant cause of adult blindness in the non-elderly and the leading cause of non-traumatic amputation in adults, and diabetic nephropathy is the main illness requiring renal dialysis in the United States.^[5]

Diabetes mellitus
Types of Diabetes
Diabetes mellitus type 1 Diabetes mellitus type 2 Gestational diabetes Pre-diabetes: Impaired fasting glycaemia Impaired glucose tolerance
Disease Management
Diabetes management: •Diabetic diet •Anti-diabetic drugs •Conventional insulinotherapy •Intensive insulinotherapy
Treatment
Treatment goals Cure for diabetes mellitus type 1 Blood glucose monitoring Modifying Diet - Diabetic diet Exercise Anti-diabetic drugs Oral drugs Commonly Used Injectable peptide analogs Insulin preparations Antihypertensive agents ACE inhibitors Hypolipidemic agents Gastric bypass surgery
Other Concerns
Cardiovascular disease Diabetic comas: •Diabetic hypoglycemia •Diabetic ketoacidosis •Nonketotic hyperosmolar Diabetic myonecrosis Diabetic nephropathy Diabetic neuropathy Diabetic retinopathy Diabetes and pregnancy
Blood tests
Blood sugar Fructosamine Glucose tolerance test Glycosylated hemoglobin

Contents 1 Classification 1.1 Type 1 diabetes 1.2 Type 2 diabetes 1.3 Gestational diabetes 1.4 Other types 2 Signs and symptoms 3 Genetics 4 Pathophysiology 5 Diagnosis 6 Screening 7 Prevention 8 Treatment and management 9 Cure 9.1 Cures for type 1 diabetes 9.2 Cures for type 2 diabetes 10 Complications and prognosis 10.1 Acute complications 10.2 Chronic complications 11 Epidemiology 12 History 13 Social issues 14 See also 15 References 16 External links

Classification

The term diabetes, without qualification, usually refers to diabetes mellitus, which is associated with excessive sweet urine (known as "glycosuria") but there are several rarer conditions also named diabetes. The most common of these is diabetes insipidus in which the urine is not sweet (insipidus meaning "without taste" in Latin); it can be caused either by kidney (nephrogenic DI) or pituitary gland (central DI) damage. It is a noninfectious disease. Among the body systems affected are the nerve, digestive, circulatory, endocrine and urinary systems.

The World Health Organization projects that the number of diabetics will exceed 350 million by 2030. Governments and other healthcare providers around the world are investing in health education, diagnosis and treatments for this chronic, debilitating—but controllable—disorder

The term "type 1 diabetes" has universally replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes mellitus (IDDM). Likewise, the term "type 2 diabetes" has replaced several former terms, including adult-onset diabetes, obesity-related diabetes, and non-insulin-dependent diabetes mellitus (NIDDM). Beyond these two types, there is no agreed-upon standard nomenclature. Various sources have defined "type 3 diabetes" as, among others, gestational diabetes,^[6] insulin-resistant type 1 diabetes (or "double diabetes"), type 2 diabetes which has progressed to require injected insulin, and latent autoimmune diabetes of adults (or LADA or "type 1.5" diabetes.^[7])

Type 1 diabetes

Main article: Diabetes mellitus type 1

Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas leading to a deficiency of insulin. This type of diabetes can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated variety, where beta cell loss is a T-cell mediated autoimmune attack.^[8] There is no known preventive measure which can be taken against type 1 diabetes; it is about 10% of diabetes mellitus cases in North America and Europe (though this varies by geographical location), and is a higher percentage in some other areas. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Type 1 diabetes can affect children or adults but was traditionally termed "juvenile diabetes" because it represents a majority of the diabetes cases in children.

The principal treatment of type 1 diabetes, even in its earliest stages, is the delivery of artificial insulin via injection combined with careful monitoring of blood glucose levels using blood testing monitors. Without insulin, diabetic ketoacidosis often develops which may result in coma or death. Treatment emphasis is now also placed on lifestyle adjustments (diet and exercise) though these cannot reverse the progress of the disease. Apart from the common subcutaneous injections, it is also possible to deliver insulin by a pump, which allows continuous infusion of insulin 24 hours a day at preset levels, and the ability to program doses (a bolus) of insulin as needed at meal times. An inhaled form of insulin was approved by the FDA in January 2006, although it was discontinued for business reasons in October 2007.^[9][10] Non-insulin treatments, such as monoclonal antibodies and stem-cell based therapies, are effective in animal models but have not yet completed clinical trials in humans.^[11]

Type 1 treatment must be continued indefinitely in essentially all cases. Treatment need not significantly impair normal activities, if sufficient patient training, awareness, appropriate care, discipline in testing and dosing of insulin is taken. However, treatment is burdensome for patients; insulin is replaced in a non-physiological manner, and this approach is therefore far from ideal. The average glucose level for the type 1 patient should be as close to normal (80–120 mg/dl, 4–6 mmol/l) as is safely possible. Some physicians suggest up to 140–150 mg/dl (7-7.5 mmol/l) for those having trouble with lower values, such as frequent hypoglycemic events. Values above 400 mg/dl (20 mmol/l) are sometimes accompanied by discomfort and frequent urination leading to dehydration. Values above 600 mg/dl (30 mmol/l) usually require medical treatment and may lead to ketoacidosis, although they are not immediately life-threatening. However, low levels of blood glucose, called hypoglycemia, may lead to seizures or episodes of unconsciousness and absolutely must be treated immediately, via emergency high-glucose gel placed in the patient's mouth, intravenous administration of dextrose, or an injection of glucagon.

Type 2 diabetes

Main article: Diabetes mellitus type 2

Type 2 diabetes mellitus is characterized differently and is due to insulin resistance or reduced insulin sensitivity, combined with relatively reduced insulin secretion which in some cases becomes absolute. The defective responsiveness of body tissues to insulin almost certainly involves the insulin receptor in cell membranes. However, the specific defects are not known. Diabetes mellitus due to a known specific defect are classified separately. Type 2 diabetes is the most common type.

In the early stage of type 2 diabetes, the predominant abnormality is reduced insulin sensitivity, characterized by elevated levels of insulin in the blood. At this stage hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver. As the disease progresses, the impairment of insulin secretion worsens, and therapeutic replacement of insulin often becomes necessary.

There are numerous theories as to the exact cause and mechanism in type 2 diabetes. Central obesity (fat concentrated around the waist in relation to abdominal organs, but not subcutaneous fat) is known to predispose individuals to insulin resistance. Abdominal fat is especially active hormonally, secreting a group of hormones called adipokines that may possibly impair glucose tolerance. Obesity is found in approximately 55% of patients diagnosed with type 2 diabetes.^[12] Other factors include aging (about 20% of elderly patients in North America have diabetes) and family history (type 2 is much more common in those with close relatives who have had it). In the last decade, type 2 diabetes has increasingly begun to affect children and adolescents, probably in connection with the increased prevalence of childhood obesity seen in recent decades in some places.^[13] Environmental exposures may contribute to recent increases in the rate of type 2 diabetes. A positive correlation has been found between the concentration in the urine of bisphenol A, a constituent of polycarbonate plastic from some producers, and the incidence of type 2 diabetes.^[14]

Type 2 diabetes may go unnoticed for years because visible symptoms are typically mild, non-existent or sporadic, and usually there are no ketoacidotic episodes. However, severe long-term complications can result from unnoticed type 2 diabetes, including renal failure due to diabetic nephropathy, vascular disease (including coronary artery disease), vision damage due to diabetic retinopathy, loss of sensation or pain due to diabetic neuropathy, liver damage from non-alcoholic steatohepatitis and heart failure from diabetic cardiomyopathy.

Type 2 diabetes is usually first treated by increasing physical activity, decreasing carbohydrate intake, and losing weight. These can restore insulin sensitivity even when the weight loss is modest, for example around 5 kg (10 to 15 lb), most especially when it is in abdominal fat deposits. It is sometimes possible to achieve long-term, satisfactory glucose control with these measures alone. However, the underlying tendency to insulin resistance is not lost, and so attention to diet, exercise, and weight loss must continue. The usual next step, if necessary, is treatment with oral antidiabetic drugs. Insulin production is initially only moderately impaired in type 2 diabetes, so oral medication (often used in various combinations) can be used to improve insulin production (e.g., sulfonylureas), to regulate inappropriate release of glucose by the liver and attenuate insulin resistance to some extent (e.g., metformin), and to substantially attenuate insulin resistance (e.g., thiazolidinediones). According to one study, overweight patients treated with metformin compared with diet alone, had relative risk reductions of 32% for any diabetes endpoint, 42% for diabetes related death and 36% for all cause mortality and stroke.^[15] Oral medication may eventually fail due to further impairment of beta cell insulin secretion. At this point, insulin therapy is necessary to maintain normal or near normal glucose levels.

Gestational diabetes

Main article: Gestational diabetes

Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2%–5% of all pregnancies and may improve or disappear after delivery. Gestational diabetes is fully treatable but requires careful medical supervision throughout the pregnancy. About 20%–50% of affected women develop type 2 diabetes later in life.

Even though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital cardiac and central nervous system anomalies, and skeletal muscle malformations. Increased fetal insulin may inhibit fetal surfactant production and cause respiratory distress syndrome. Hyperbilirubinemia may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Induction may be indicated with decreased placental function. A cesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.

A 2008 study completed in the U.S. found that more American women are entering pregnancy with preexisting diabetes. In fact the rate of diabetes in expectant mothers has more than doubled in the past 6 years.^[16] This is particularly problematic as diabetes raises the risk of complications during pregnancy, as well as increasing the potential that the children of diabetic mothers will also become diabetic in the future.

Other types

Most cases of diabetes mellitus fall into the two broad etiologic categories of type 1 or type 2 diabetes. However, many types of diabetes mellitus have more specific known causes, and thus fall into more specific categories. As more research is done into diabetes, many patients who were previously diagnosed as type 1 or type 2 diabetes will have their condition reclassified.

Some cases of diabetes are caused by the body's tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type 2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells. The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (MRDM or MMDM, ICD-10 code E12), was deprecated by the World Health Organization when the current taxonomy was introduced in 1999.^[17]

Signs and symptoms

Overview of the most significant symptoms of diabetes.

The classical symptoms are polyuria and polydipsia which are, respectively, frequent urination and increased thirst and consequent increased fluid intake. Symptoms may develop quite rapidly (weeks or months) in type 1 diabetes, particularly in children. However, in type 2 diabetes symptoms usually develop much more slowly and may be subtle or completely absent. Type 1 diabetes may also cause a rapid yet significant weight loss (despite normal or even increased eating) and irreducible mental fatigue. All of these symptoms except weight loss can also manifest in type 2 diabetes in patients whose diabetes is poorly controlled, although unexplained weight loss may be experienced at the onset of the disease. Final diagnosis is made by measuring the blood glucose concentration.

When the glucose concentration in the blood is raised beyond its renal threshold, reabsorption of glucose in the proximal renal tubuli is incomplete, and part of the glucose remains in the urine (glycosuria). This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume will be replaced osmotically from water held in body cells and other body compartments, causing dehydration and increased thirst.

Prolonged high blood glucose causes glucose absorption, which leads to changes in the shape of the lenses of the eyes, resulting in vision changes; sustained sensible glucose control usually returns the lens to its original shape. Blurred vision is a common complaint leading to a diabetes diagnosis; type 1 should always be suspected in cases of rapid vision change, whereas with type 2 change is generally more gradual, but should still be suspected.

Patients (usually with type 1 diabetes) may also initially present with diabetic ketoacidosis (DKA), an extreme state of metabolic dysregulation characterized by the smell of acetone on the patient's breath; a rapid, deep breathing known as Kussmaul breathing; polyuria; nausea; vomiting and abdominal pain; and any of many altered states of consciousness or arousal (such as hostility and mania or, equally, confusion and lethargy). In severe DKA, coma may follow, progressing to death. Diabetic ketoacidosis is a medical emergency and requires immediate hospitalization.

A rarer but equally severe possibility is hyperosmolar nonketotic state, which is more common in type 2 diabetes and is mainly the result of dehydration due to loss of body water. Often, the patient has been drinking extreme amounts of sugar-containing drinks, leading to a vicious circle in regard to the water loss.

Genetics

Both type 1 and type 2 diabetes are at least partly inherited. Type 1 diabetes appears to be triggered by some (mainly viral) infections, or less commonly, by stress or environmental exposure (such as exposure to certain chemicals or drugs). There is a genetic element in individual susceptibility to some of these triggers which has been traced to particular HLA genotypes (i.e., the genetic "self" identifiers relied upon by the immune system). However, even in those who have inherited the susceptibility, type 1 diabetes mellitus seems to require an environmental trigger. There is also maturity onset diabetes of the young (MODY) which is a group of several single gene (monogenic) disorders with strong heritability patterns which present as type 2 diabetes early in life, usually before 30 years, and sometimes in childhood.

There is a stronger inheritance pattern for type 2 diabetes. Those with first-degree relatives with type 2 have a much higher risk of developing type 2, increasing with the number of those relatives. Concordance among monozygotic twins is close to 100%, and about 25% of those with the disease have a family history of diabetes. Genes significantly associated with developing type 2 diabetes, include TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX.^[18] KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11), encodes the islet ATP-sensitive potassium channel Kir6.2, and TCF7L2 (transcription factor 7–like 2) regulates proglucagon gene expression and thus the production of glucagon-like peptide-1.^[8] Moreover, obesity (which is an independent risk factor for type 2 diabetes) is strongly inherited.^[19]

Monogenic forms, e.g., MODY, constitute 1-5 % of all cases.^[20]

Various hereditary conditions may feature diabetes, for example myotonic dystrophy and Friedreich's ataxia. Wolfram's syndrome is an autosomal recessive neurodegenerative disorder that first becomes evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD.^[21]

Pathophysiology

Mechanism of insulin release in normal pancreatic beta cells. Insulin production is more or less constant within the beta cells, irrespective of blood glucose levels. It is stored within vacuoles pending release, via exocytosis, which is primarily triggered by food, chiefly food containing absorbable glucose. The chief trigger is a rise in blood glucose levels after eating

Insulin is the principal hormone that regulates uptake of glucose from the blood into most cells (primarily muscle and fat cells, but not central nervous system cells). Therefore deficiency of insulin or the insensitivity of its receptors plays a central role in all forms of diabetes mellitus.

Most of the carbohydrates in food are converted within a few hours to the monosaccharide glucose, the principal carbohydrate found in blood and used by the body as fuel. The most significant exceptions are fructose, most disaccharides (except sucrose and in some people lactose), and all more complex polysaccharides, with the outstanding exception of starch. Insulin is released into the blood by beta cells (β-cells), found in the Islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the body's cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage.

Insulin is also the principal control signal for conversion of glucose to glycogen for internal storage in liver and muscle cells. Lowered glucose levels result both in the reduced release of insulin from the beta cells and in the reverse conversion of glycogen to glucose when glucose levels fall. This is mainly controlled by the hormone glucagon which acts in an opposite manner to insulin. Glucose thus recovered by the liver re-enters the bloodstream; muscle cells lack the necessary export mechanism.

Higher insulin levels increase some anabolic ("building up") processes such as cell growth and duplication, protein synthesis, and fat storage. Insulin (or its lack) is the principal signal in converting many of the bidirectional processes of metabolism from a catabolic to an anabolic direction, and vice versa. In particular, a low insulin level is the trigger for entering or leaving ketosis (the fat burning metabolic phase).

If the amount of insulin available is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or resistance), or if the insulin itself is defective, then glucose will not be absorbed properly by those body cells that require it nor will it be stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as acidosis.

Diagnosis

The diagnosis of type 1 diabetes, and many cases of type 2, is usually prompted by recent-onset symptoms of excessive urination (polyuria) and excessive thirst (polydipsia), often accompanied by weight loss. These symptoms typically worsen over days to weeks; about a quarter of people with new type 1 diabetes have developed some degree of diabetic ketoacidosis by the time the diabetes is recognized. The diagnosis of other types of diabetes is usually made in other ways. These include ordinary health screening; detection of hyperglycemia during other medical investigations; and secondary symptoms such as vision changes or unexplainable fatigue. Diabetes is often detected when a person suffers a problem that is frequently caused by diabetes, such as a heart attack, stroke, neuropathy, poor wound healing or a foot ulcer, certain eye problems, certain fungal infections, or delivering a baby with macrosomia or hypoglycemia.

Diabetes mellitus is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of the following:^[17]

• Fasting plasma glucose level at or above 126 mg/dL (7.0 mmol/l).
• Plasma glucose at or above 200 mg/dL (11.1 mmol/l) two hours after a 75 g oral glucose load as in a glucose tolerance test.
• Symptoms of hyperglycemia and casual plasma glucose at or above 200 mg/dL (11.1 mmol/l).

A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above-listed methods on a different day. Most physicians prefer to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test.^[22] According to the current definition, two fasting glucose measurements above 126 mg/dL (7.0 mmol/l) is considered diagnostic for diabetes mellitus.

Patients with fasting glucose levels from 100 to 125 mg/dL (6.1 and 7.0 mmol/l) are considered to have impaired fasting glucose. Patients with plasma glucose at or above 140 mg/dL or 7.8 mmol/l, but not over 200, two hours after a 75 g oral glucose load are considered to have impaired glucose tolerance. Of these two pre-diabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus as well as cardiovascular disease.^[23]

While not used for diagnosis, an elevated level of glucose irreversibly bound to hemoglobin (termed glycosylated hemoglobin or HbA1c) of 6.0% or higher (the 2003 revised U.S. standard) is considered abnormal by most labs; HbA1c is primarily used as a treatment-tracking test reflecting average blood glucose levels over the preceding 90 days (approximately) which is the average lifetime of red blood cells which contain hemoglobin in most patients. However, some physicians may order this test at the time of diagnosis to track changes over time. The current recommended goal for HbA1c in patients with diabetes is Sniderman, AD; Bhopal R, Prabhakaran D, Sarrafzadegan N, Tchernof A (2007). "Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis". International journal of epidemiology 36 (1): 220–5. doi:10.1093/ije/dyl245. PMID 17510078. </ref>^[24]

Screening

Diabetes screening is recommended for many people at various stages of life, and for those with any of several risk factors. The screening test varies according to circumstances and local policy, and may be a random blood glucose test, a fasting blood glucose test, a blood glucose test two hours after 75 g of glucose, or an even more formal glucose tolerance test. Many healthcare providers recommend universal screening for adults at age 40 or 50, and often periodically thereafter. Earlier screening is typically recommended for those with risk factors such as obesity, family history of diabetes, high-risk ethnicity (Hispanic, Native American, Afro-Caribbean, Pacific Islander).^[25][26]

Many medical conditions are associated with diabetes and warrant screening. A partial list includes: high blood pressure, elevated cholesterol levels, coronary artery disease, past gestational diabetes, polycystic ovary syndrome, chronic pancreatitis, fatty liver, hemochromatosis, cystic fibrosis, several mitochondrial neuropathies and myopathies, myotonic dystrophy, Friedreich's ataxia, some of the inherited forms of neonatal hyperinsulinism. The risk of diabetes is higher with chronic use of several medications, including high-dose glucocorticoids, some chemotherapy agents (especially L-asparaginase), as well as some of the antipsychotics and mood stabilizers (especially phenothiazines and some atypical antipsychotics).

People with a confirmed diagnosis of diabetes are tested routinely for complications. This includes yearly urine testing for microalbuminuria and examination of the retina of the eye for retinopathy.

Prevention

Type 1 diabetes risk is known to depend upon a genetic predisposition based on HLA types (particularly types DR3 and DR4), an unknown environmental trigger (suspected to be an infection, although none has proven definitive in all cases), and an uncontrolled autoimmune response that attacks the insulin producing beta cells.^[27] Some research has suggested that breastfeeding decreased the risk in later life;^[28][29] various other nutritional risk factors are being studied, but no firm evidence has been found.^[30] Giving children 2000 IU of Vitamin D during their first year of life is associated with reduced risk of type 1 diabetes, though the causal relationship is obscure.^[31]

Children with antibodies to beta cell proteins (ie at early stages of an immune reaction to them) but no overt diabetes, and treated with vitamin B-3 (niacin), had less than half the diabetes onset incidence in a 7-year time span as did the general population, and an even lower incidence relative to those with antibodies as above, but who received no vitamin B3.^[32]

Type 2 diabetes risk can be reduced in many cases by making changes in diet and increasing physical activity.^[33][34] The American Diabetes Association (ADA) recommends maintaining a healthy weight, getting at least 2½ hours of exercise per week (several brisk sustained walks appear sufficient), having a modest fat intake, and eating sufficient fiber (e.g., from whole grains). The ADA does not recommend alcohol consumption as a preventive, but it is interesting to note that moderate alcohol intake may reduce the risk (though heavy consumption absolutely and clearly increases damage to bodily systems significantly); a similarly confused connection between low dose alcohol consumption and heart disease is termed the French Paradox.

There is inadequate evidence that eating foods of low glycemic index is clinically helpful despite recommendations and suggested diets emphasizing this approach.^[35]

There are numerous studies which suggest connections between some aspects of Type II diabetes with ingestion of certain foods or with some drugs. Some studies have shown delayed progression to diabetes in predisposed patients through prophylactic use of metformin,^[34] rosiglitazone,^[36] or valsartan.^[37] In patients on hydroxychloroquine for rheumatoid arthritis, incidence of diabetes was reduced by 77% though causal mechanisms are unclear.^[38] Breastfeeding may also be associated with the prevention of type 2 of the disease in mothers.^[39] Clear evidence for these and any of many other connections between foods and supplements and diabetes is sparse to date; none, despite secondary claims for (or against), is sufficiently well established to justify as a standard clinical approach.

Treatment and management

Main article: Diabetes management

Diabetes mellitus is currently a chronic disease, without a cure, and medical emphasis must necessarily be on managing/avoiding possible short-term as well as long-term diabetes-related problems. There is an exceptionally important role for patient education, dietetic support, sensible exercise, self monitoring of blood glucose, with the goal of keeping both short-term blood glucose levels, and long term levels as well, within acceptable bounds. Careful control is needed to reduce the risk of long term complications. This is theoretically achievable with combinations of diet, exercise and weight loss (type 2), various oral diabetic drugs (type 2 only), and insulin use (type 1 and for type 2 not responding to oral medications, mostly those with extended duration diabetes). In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications should be undertaken to control blood pressure^[40] and cholesterol by exercising more, smoking less or ideally not at all, consuming an appropriate diet, wearing diabetic socks, wearing diabetic shoes, and if necessary, taking any of several drugs to reduce blood pressure. Many type 1 treatments include combination use of regular or NPH insulin, and/or synthetic insulin analogs (e.g., Humalog, Novolog or Apidra) in combinations such as Lantus/Levemir and Humalog, Novolog or Apidra. Another type 1 treatment option is the use of the insulin pump (e.g., from Deltec Cozmo, Animas, Medtronic Minimed, Insulet Omnipod, or ACCU-CHEK). A blood lancet is used to pierce the skin (typically of a finger), in order to draw blood to test it for sugar levels.

In countries using a general practitioner system, such as the United Kingdom, care may take place mainly outside hospitals, with hospital-based specialist care used only in case of complications, difficult blood sugar control, or research projects. In other circumstances, general practitioners and specialists share care of a patient in a team approach. Optometrists, podiatrists/chiropodists, dietitians, physiotherapists, nursing specialists (e.g., DSNs (Diabetic Specialist Nurse)), nurse practitioners, or Certified Diabetes Educators, may jointly provide multidisciplinary expertise. In countries where patients must provide their own health care (i.e., in the developed world, the US, and in much of the undeveloped world), the impact of out-of-pocket costs of adequate diabetic care can be very high. In addition to the medications and supplies needed, patients are often advised to receive regular consultation from a physician (e.g., at least every three to six months).

Peer support links people living with diabetes. Within peer support, people with a common illness share knowledge and experience that others, including many health workers, do not have. Peer support is frequent, ongoing, accessible and flexible and can take many forms—phone calls, text messaging, group meetings, home visits, and even grocery shopping. It complements and enhances other health care services by creating the emotional, social and practical assistance necessary for managing disease and staying healthy.

Cure

Cures for type 1 diabetes

Main article: Cure for diabetes mellitus type 1

There is no practical cure, at this time, for type 1 diabetes. The fact that type 1 diabetes is due to the failure of one of the cell types of a single organ with a relatively simple function (i.e. the failure of the beta cells in the Islets of Langerhans) has led to the study of several possible schemes to cure this form of diabetes mostly by replacing the pancreas or just the beta cells.^[41] Only those type 1 diabetics who have received either a pancreas or a kidney-pancreas transplant (often when they have developed diabetic kidney disease (ie, nephropathy) and become insulin-independent) may now be considered "cured" from their diabetes. A simultaneous pancreas-kidney transplant is a promising solution, showing similar or improved survival rates over a kidney transplant alone.^[42] Still, they generally remain on long-term immunosuppressive drugs and there is a possibility that the immune system will mount a host versus graft response against the transplanted organ.^[41]

Transplants of exogenous beta cells have been performed experimentally in both mice and humans, but this measure is not yet practical in regular clinical practice partly due to the limited number of beta cell donors. Thus far, like any such transplant, it has provoked an immune reaction and long-term immunosuppressive drugs have been needed to protect the transplanted tissue.^[43] An alternative technique has been proposed to place transplanted beta cells in a semi-permeable container, isolating and protecting them from the immune system. Stem cell research has also been suggested as a potential avenue for a cure since it may permit regrowth of Islet cells which are genetically part of the treated individual, thus perhaps eliminating the need for immuno-suppressants.^[41] This new method, autologous nonmyeloablative HSTC, was recently developed by a research team composed of scientists from the US and Brazil. This was originally tested in mice and in 2007 there was the first trial with fifteen patients. Recently this trial was continued and 8 more patients were added. In the trial, the researchers implanted diabetes type 1 patients with their own stem cells raised from their own bone marrow. The stem cell transplant led to an appreciable repopulation of functioning insulin-producing beta cells in the pancreas so the patients became insulin free. Most of these patients became insulin independent for a mean period of 18.8 months. At the present time, autologous nonmyeloablative HSCT remains the only treatment capable of reversing type 1 DM in humans.^[44]

Microscopic or nanotechnological approaches are under investigation as well, in one proposed case with implanted stores of insulin metered out by a rapid response valve sensitive to blood glucose levels. At least two approaches have been demonstrated in vitro. These are, in some sense, closed-loop insulin pumps.

Cures for type 2 diabetes

Type 2 has had no definitive cure, although recently it has been shown that a type of gastric bypass surgery can normalize blood glucose levels in 80-100% of severely obese patients with diabetes. The precise causal mechanisms are being intensively researched; its results are not simply attributable to weight loss, as the improvement in blood sugars precedes any change in body mass. This approach may become a standard treatment for some people with type 2 diabetes in the relatively near future.^[45] This surgery has the additional benefit of reducing the death rate from all causes by up to 40% in severely obese people.^[46] A small number of normal to moderately obese patients with type 2 diabetes have successfully undergone similar operations.^[47][48]

Complications and prognosis

Patient education, understanding, and participation is vital since the complications of diabetes are far less common and less severe in people who have well-controlled blood sugar levels.^[49][50] Wider health problems accelerate the deleterious effects of diabetes. These include smoking, elevated cholesterol levels, obesity, high blood pressure, and lack of regular exercise. According to one study, women with high blood pressure (hypertension) were three times more likely to develop type 2 diabetes as compared with women with optimal BP after adjusting for various factors such as age, ethnicity, smoking, alcohol intake, body mass index (BMI), exercise, family history of diabetes, etc.^[51] The study was conducted by researchers from the Brigham and Women’s Hospital, Harvard Medical School and the Harvard School of Public Health, USA, who followed over 38,000 female health professionals for ten years.

Anecdotal evidence suggests that some of those with type 2 diabetes who exercise regularly, lose weight, and eat healthy diets may be able to keep some of the disease or some of the effects of the disease in 'remission.' Certainly these tips can help prevent people predisposed to type 2 diabetes and those at pre-diabetic stages from actually developing the disorder as it helps restore insulin sensitivity. However patients should talk to their doctors about this for real expectations before undertaking it (esp. to avoid hypoglycemia or other complications); few people actually seem to go into total 'remission,' but some may find they need less of their insulin medications since the body tends to have lower insulin requirements during and shortly following exercise. Regardless of whether it works that way or not for an individual, there are certainly other benefits to this healthy lifestyle for both diabetics and nondiabetics.

The way diabetes is managed changes with age. Insulin production decreases because of age-related impairment of pancreatic beta cells. Additionally, insulin resistance increases because of the loss of lean tissue and the accumulation of fat, particularly intra-abdominal fat, and the decreased tissue sensitivity to insulin. Glucose tolerance progressively declines with age, leading to a high prevalence of type 2 diabetes and postchallenge hyperglycemia in the older population.^[52] Age-related glucose intolerance in humans is often accompanied by insulin resistance, but circulating insulin levels are similar to those of younger people.^[53] Treatment goals for older patients with diabetes vary with the individual, and take into account health status, as well as life expectancy, level of dependence, and willingness to adhere to a treatment regimen.^[54]

Acute complications

Main articles: Diabetic ketoacidosis, nonketotic hyperosmolar coma, hypoglycemia, and diabetic coma

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is an acute and dangerous complication that is always a medical emergency. Low insulin levels cause the liver to turn to fat for fuel (ie, ketosis); ketone bodies are intermediate substrates in that metabolic sequence. This is normal when periodic, but can become a serious problem if sustained. Elevated levels of ketone bodies in the blood decrease the blood's pH, leading to DKA. On presentation at hospital, the patient in DKA is typically dehydrated, and breathing rapidly and deeply. Abdominal pain is common and may be severe. The level of consciousness is typically normal until late in the process, when lethargy may progress to coma. Ketoacidosis can easily become severe enough to cause hypotension, shock, and death. Urine analysis will reveal significant levels of ketone bodies (which have exceeded their renal threshold blood levels to appear in the urine, often before other overt symptoms). Prompt, proper treatment usually results in full recovery, though death can result from inadequate or delayed treatment, or from complications (e.g., brain edema). DKA is always a medical emergency and requires medical attention. Ketoacidosis is much more common in type 1 diabetes than type 2.

Hyperglycemia hyperosmolar state

Hyperosmolar nonketotic state (HNS) is an acute complication sharing many symptoms with DKA, but an entirely different origin and different treatment. A person with very high (usually considered to be above 300 mg/dl (16 mmol/l)) blood glucose levels, water is osmotically drawn out of cells into the blood and the kidneys eventually begin to dump glucose into the urine. This results in loss of water and an increase in blood osmolarity. If fluid is not replaced (by mouth or intravenously), the osmotic effect of high glucose levels, combined with the loss of water, will eventually lead to dehydration. The body's cells become progressively dehydrated as water is taken from them and excreted. Electrolyte imbalances are also common and are always dangerous. As with DKA, urgent medical treatment is necessary, commonly beginning with fluid volume replacement. Lethargy may ultimately progress to a coma, though this is more common in type 2 diabetes than type 1.

Hypoglycemia

Hypoglycemia, or abnormally low blood glucose, is an acute complication of several diabetes treatments. It is rare otherwise, either in diabetic or non-diabetic patients. The patient may become agitated, sweaty, and have many symptoms of sympathetic activation of the autonomic nervous system resulting in feelings akin to dread and immobilized panic. Consciousness can be altered or even lost in extreme cases, leading to coma, seizures, or even brain damage and death. In patients with diabetes, this may be caused by several factors, such as too much or incorrectly timed insulin, too much or incorrectly timed exercise (exercise decreases insulin requirements) or not enough food (specifically glucose containing carbohydrates). The variety of interactions makes cause identification difficult in many instances.

It is more accurate to note that iatrogenic hypoglycemia is typically the result of the interplay of absolute (or relative) insulin excess and compromised glucose counterregulation in type 1 and advanced type 2 diabetes. Decrements in insulin, increments in glucagon, and, absent the latter, increments in epinephrine are the primary glucose counterregulatory factors that normally prevent or (more or less rapidly) correct hypoglycemia. In insulin-deficient diabetes (exogenous) insulin levels do not decrease as glucose levels fall, and the combination of deficient glucagon and epinephrine responses causes defective glucose counterregulation.

Furthermore, reduced sympathoadrenal responses can cause hypoglycemia unawareness. The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes posits that recent incidents of hypoglycemia causes both defective glucose counterregulation and hypoglycemia unawareness. By shifting glycemic thresholds for the sympathoadrenal (including epinephrine) and the resulting neurogenic responses to lower plasma glucose concentrations, antecedent hypoglycemia leads to a vicious cycle of recurrent hypoglycemia and further impairment of glucose counterregulation. In many cases (but not all), short-term avoidance of hypoglycemia reverses hypoglycemia unawareness in affected patients, although this is easier in theory than in clinical experience.

In most cases, hypoglycemia is treated with sugary drinks or food. In severe cases, an injection of glucagon (a hormone with effects largely opposite to those of insulin) or an intravenous infusion of dextrose is used for treatment, but usually only if the person is unconscious. In any given incident, glucagon will only work once as it uses stored liver glycogen as a glucose source; in the absence of such stores, glucagon is largely ineffective. In hospitals, intravenous dextrose is often used.

Chronic complications

Vascular disease

Chronic elevation of blood glucose level leads to damage of blood vessels (angiopathy). The endothelial cells lining the blood vessels take in more glucose than normal, since they don't depend on insulin. They then form more surface glycoproteins than normal, and cause the basement membrane to grow thicker and weaker. In diabetes, the resulting problems are grouped under "microvascular disease" (due to damage to small blood vessels) and "macrovascular disease" (due to damage to the arteries).

Image of fundus showing scatter laser surgery for diabetic retinopathy

The damage to small blood vessels leads to a microangiopathy, which can cause one or more of the following:

• Diabetic retinopathy, growth of friable and poor-quality new blood vessels in the retina as well as macular edema (swelling of the macula), which can lead to severe vision loss or blindness. Retinal damage (from microangiopathy) makes it the most common cause of blindness among non-elderly adults in the US.
• Diabetic neuropathy, abnormal and decreased sensation, usually in a 'glove and stocking' distribution starting with the feet but potentially in other nerves, later often fingers and hands. When combined with damaged blood vessels this can lead to diabetic foot (see below). Other forms of diabetic neuropathy may present as mononeuritis or autonomic neuropathy. Diabetic amyotrophy is muscle weakness due to neuropathy.
• Diabetic nephropathy, damage to the kidney which can lead to chronic renal failure, eventually requiring dialysis. Diabetes mellitus is the most common cause of adult kidney failure worldwide in the developed world.
• Diabetic cardiomyopathy, damage to the heart, leading to diastolic dysfunction and eventually heart failure.

Macrovascular disease leads to cardiovascular disease, to which accelerated atherosclerosis is a contributor:

• Coronary artery disease, leading to angina or myocardial infarction ("heart attack")
• Stroke (mainly the ischemic type)
• Peripheral vascular disease, which contributes to intermittent claudication (exertion-related leg and foot pain) as well as diabetic foot.
• Diabetic myonecrosis ('muscle wasting')

Diabetic foot, often due to a combination of sensory neuropathy (numbness or insensitivity) and vascular damage, increases rates of skin ulcers and infection and, in serious cases, necrosis and gangrene. It is why diabetics are prone to leg and foot infections and why it takes longer for them to heal from leg and foot wounds. It is the most common cause of non-traumatic adult amputation, usually of toes and or feet, in the developed world.

Carotid artery stenosis does not occur more often in diabetes, and there appears to be a lower prevalence of abdominal aortic aneurysm. However, diabetes does cause higher morbidity, mortality and operative risks with these conditions.^[55]

Diabetic encephalopathy^[56] is the increased cognitive decline and risk of dementia observed in diabetes. Various mechanisms are proposed, including alterations to the vascular supply of the brain and the interaction of insulin with the brain itself.^[57]

Epidemiology

In 2000, according to the World Health Organization, at least 171 million people worldwide suffer from diabetes, or 2.8% of the population.^[58] Its incidence is increasing rapidly, and it is estimated that by the year 2030, this number will almost double.^[58] Diabetes mellitus occurs throughout the world, but is more common (especially type 2) in the more developed countries. The greatest increase in prevalence is, however, expected to occur in Asia and Africa, where most patients will probably be found by 2030.^[58] The increase in incidence of diabetes in developing countries follows the trend of urbanization and lifestyle changes, perhaps most importantly a "Western-style" diet. This has suggested an environmental (i.e., dietary) effect, but there is little understanding of the mechanism(s) at present, though there is much speculation, some of it most compellingly presented.^[58]

For at least 20 years, diabetes rates in North America have been increasing substantially. In 2008 there were about 24 million people with diabetes in the United States alone, from those 5.7 million people remain undiagnosed. Other 57 million people are estimated to have pre-diabetes.^[59]

The Centers for Disease Control has termed the change an epidemic.^[60] The National Diabetes Information Clearinghouse estimates that diabetes costs $132 billion in the United States alone every year. About 5%–10% of diabetes cases in North America are type 1, with the rest being type 2. The fraction of type 1 in other parts of the world differs; this is probably due to both differences in the rate of type 1 and differences in the rate of other types, most prominently type 2. Most of this difference is not currently understood. The American Diabetes Association cite the 2003 assessment of the National Center for Chronic Disease Prevention and Health Promotion (Centers for Disease Control and Prevention) that 1 in 3 Americans born after 2000 will develop diabetes in their lifetime.^[61][62]

According to the American Diabetes Association, approximately 18.3% (8.6 million) of Americans age 60 and older have diabetes.^[63] Diabetes mellitus prevalence increases with age, and the numbers of older persons with diabetes are expected to grow as the elderly population increases in number. The National Health and Nutrition Examination Survey (NHANES III) demonstrated that, in the population over 65 years old, 18% to 20% have diabetes, with 40% having either diabetes or its precursor form of impaired glucose tolerance.^[52]

Indigenous populations in first world countries have a higher prevalence and increasing incidence of diabetes than their corresponding non-indigenous populations. In Australia the age-standardised prevalence of self-reported diabetes in Indigenous Australians is almost 4 times that of non-indigenous Australians.^[64] Preventative community health programs such as Sugar Man (diabetes education) are showing some success in tackling this problem.

History

The term diabetes (Greek: διαβήτης, diabētēs) was coined by Aretaeus of Cappadocia. It was derived from the Greek verb διαβαίνειν, diabaínein, itself formed from the prefix dia-, "across, apart," and the verb bainein, "to walk, stand." The verb diabeinein meant "to stride, walk, or stand with legs asunder"; hence, its derivative diabētēs meant "one that straddles," or specifically "a compass, siphon." The sense "siphon" gave rise to the use of diabētēs as the name for a disease involving the discharge of excessive amounts of urine. Diabetes is first recorded in English, in the form diabete, in a medical text written around 1425. In 1675, Thomas Willis added the word mellitus, from the Latin meaning "honey", a reference to the sweet taste of the urine. This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and Persians. In 1776, Matthew Dobson confirmed that the sweet taste was because of an excess of a kind of sugar in the urine and blood of people with diabetes.^[65]

Diabetes mellitus appears to have been a death sentence in the ancient era. Hippocrates makes no mention of it, which may indicate that he felt the disease was incurable. Aretaeus did attempt to treat it but could not give a good prognosis; he commented that "life (with diabetes) is short, disgusting and painful."^[66]

Sushruta (6th century BCE) identified diabetes and classified it as Medhumeha.^[67] He further identified it with obesity and sedentary lifestyle, advising exercises to help "cure" it.^[67] The ancient Indians tested for diabetes by observing whether ants were attracted to a person's urine, and called the ailment "sweet urine disease" (Madhumeha). The Korean, Chinese, and Japanese words for diabetes are based on the same ideographs (糖尿病) which mean "sugar urine disease".

In medieval Persia, Avicenna (980-1037) provided a detailed account on diabetes mellitus in The Canon of Medicine, "describing the abnormal appetite and the collapse of sexual functions and he documented the sweet taste of diabetic urine." Like Aretaeus before him, Avicenna recognized a primary and secondary diabetes. He also described diabetic gangrene, and treated diabetes using a mixture of lupine, trigonella (fenugreek), and zedoary seed, which produces a considerable reduction in the excretion of sugar, a treatment which is still prescribed in modern times. Avicenna also "described diabetes insipidus very precisely for the first time", though it was later Johann Peter Frank (1745-1821) who first differentiated between diabetes mellitus and diabetes insipidus.^[68]

Although diabetes has been recognized since antiquity, and treatments of various efficacy have been known in various regions since the Middle Ages, and in legend for much longer, pathogenesis of diabetes has only been understood experimentally since about 1900.^[69] The discovery of a role for the pancreas in diabetes is generally ascribed to Joseph von Mering and Oskar Minkowski, who in 1889 found that dogs whose pancreas was removed developed all the signs and symptoms of diabetes and died shortly afterwards.^[70] In 1910, Sir Edward Albert Sharpey-Schafer suggested that people with diabetes were deficient in a single chemical that was normally produced by the pancreas—he proposed calling this substance insulin, from the Latin insula, meaning island, in reference to the insulin-producing islets of Langerhans in the pancreas.^[69]

The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was not further clarified until 1921, when Sir Frederick Grant Banting and Charles Herbert Best repeated the work of Von Mering and Minkowski, and went further to demonstrate they could reverse induced diabetes in dogs by giving them an extract from the pancreatic islets of Langerhans of healthy dogs.^[71] Banting, Best, and colleagues (especially the chemist Collip) went on to purify the hormone insulin from bovine pancreases at the University of Toronto. This led to the availability of an effective treatment—insulin injections—and the first patient was treated in 1922. For this, Banting and laboratory director MacLeod received the Nobel Prize in Physiology or Medicine in 1923; both shared their Prize money with others in the team who were not recognized, in particular Best and Collip. Banting and Best made the patent available without charge and did not attempt to control commercial production. Insulin production and therapy rapidly spread around the world, largely as a result of this decision. Banting is honored by World Diabetes Day which is held on his birthday, November 14.

The distinction between what is now known as type 1 diabetes and type 2 diabetes was first clearly made by Sir Harold Percival (Harry) Himsworth, and published in January 1936.^[72]

Despite the availability of treatment, diabetes has remained a major cause of death. For instance, statistics reveal that the cause-specific mortality rate during 1927 amounted to about 47.7 per 100,000 population in Malta.^[73]

Other landmark discoveries include:^[69]

• Identification of the first of the sulfonylureas in 1942
• Reintroduction of the use of biguanides for Type 2 diabetes in the late 1950s. The initial phenformin was withdrawn worldwide (in the U.S. in 1977) due to its potential for sometimes fatal lactic acidosis and metformin was first marketed in France in 1979, but not until 1994 in the US.
• The determination of the amino acid sequence of insulin (by Sir Frederick Sanger, for which he received a Nobel Prize)
• The radioimmunoassay for insulin, as discovered by Rosalyn Yalow and Solomon Berson (gaining Yalow the 1977 Nobel Prize in Physiology or Medicine)^[74]
• The three-dimensional structure of insulin (PDB 2INS)
• Dr Gerald Reaven's identification of the constellation of symptoms now called metabolic syndrome in 1988
• Demonstration that intensive glycemic control in type 1 diabetes reduces chronic side effects more as glucose levels approach 'normal' in a large longitudinal study,^[75] and also in type 2 diabetics in other large studies
• Identification of the first thiazolidinedione as an effective insulin sensitizer during the 1990s

In 1980, U.S. biotech company Genentech developed human insulin. The insulin is isolated from genetically altered bacteria (the bacteria contain the human gene for synthesizing human insulin), which produce large quantities of insulin. Scientists then purify the insulin and distribute it to pharmacies for use by diabetes patients.

Social issues

The 1990 "St Vincent Declaration"^[76][77] was the result of international efforts to improve the care accorded to those with diabetes. Doing so is important both in terms of quality of life and life expectancy but also economically-expenses due to diabetes have been shown to be a major drain on health-and productivity-related resources for healthcare systems and governments.

Several countries established more and less successful national diabetes programmes to improve treatment of the disease.^[78]

A study shows that diabetic patients with neuropathic symptoms such as numbness or tingling in feet or hands are twice as likely to be unemployed as those without the symptoms.^[79]

See also

• Blood sugar
• Diabetic dermadromes
• Diabetic foot ulcer healing
• List of terms associated with diabetes

References

1. ^ "Diabetes Blue Circle Symbol". International Diabetes Federation. 17 March 2006. http://www.diabetesbluecircle.org. 
2. ^ "Diabetes Mellitus." American Heart Association. July 1, 2009. http://www.americanheart.org/presenter.jhtml?identifier=4546
3. ^ ^{a b c d} "All About Diabetes." American Diabetes Association. July 1, 2009. http://www.diabetes.org/about-diabetes.jsp
4. ^ Handelsman, Yehuda, MD. "A Doctor's Diagnosis: Prediabetes." Power of Prevention, Vol 1, Issue 2, 2009.
5. ^ Mailloux, Lionel (2007-02-13). "UpToDate Dialysis in diabetic nephropathy". UpToDate. http://patients.uptodate.com/topic.asp?file=dialysis/15147. Retrieved on 2007-12-07. 
6. ^ "Other "types" of diabetes". American Diabetes Association. August 25, 2005. http://www.diabetes.org/other-types.jsp. 
7. ^ "Diseases: Johns Hopkins Autoimmune Disease Research Center". http://autoimmune.pathology.jhmi.edu/diseases.cfm?systemID=3&DiseaseID=23. Retrieved on 2007-09-23. 
8. ^ ^{a b} Rother, KI (2007). "Diabetes Treatment — Bridging the Divide". N Engl J Med 356 (15): 1499–1501. doi:10.1056/NEJMp078030. PMID 17429082. http://content.nejm.org/cgi/content/full/356/15/1499. 
9. ^ "FDA Approves First Ever Inhaled Insulin Combination Product for Treatment of Diabetes". http://www.fda.gov/bbs/topics/news/2006/NEW01304.html. Retrieved on 2007-09-09. 
10. ^ "MannKind Unveils Proposed Trade Name at Dedication of Danbury Manufacturing Facility". http://www.mannkindcorp.com/pressreleasetext.aspx?releaseID=1198182. Retrieved on 2008-10-23. 
11. ^ Baillie, K (2008-07-05). "ClinicLog article on current diabetes trials.". ClinicLog.com. http://www.cliniclog.com/type_1_diabetes_trials.php. Retrieved on 2008-07-23. 
12. ^ Eberhart MS, Ogden C, Engelgau M, Cadwell B, Hedley AA, Saydah SH (November 2004). "Prevalence of overweight and obesity among adults with diagnosed diabetes—United States, 1988-1994 and 1999-2002". MMWR Morb. Mortal. Wkly. Rep. 53 (45): 1066–8. PMID 15549021. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5345a2.htm. 
13. ^ Arlan Rosenbloom, Janet H Silverstein (2003). Type 2 Diabetes in Children and Adolescents: A Clinician's Guide to Diagnosis, Epidemiology, Pathogenesis, Prevention, and Treatment. American Diabetes Association,U.S.. pp. 1. ISBN 978-1580401555. 
14. ^ Lang IA, Galloway TS, Scarlett A, et al. (September 2008). "Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults". JAMA 300 (11): 1303–10. doi:10.1001/jama.300.11.1303. PMID 18799442. 
15. ^ "Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group". Lancet 352 (9131): 854–65. 1998. doi:10.1016/S0140-6736(98)07037-8. PMID 9742977. 
16. ^ Lawrence JM, Contreras R, Chen W, Sacks DA (May 2008). "Trends in the prevalence of preexisting diabetes and gestational diabetes mellitus among a racially/ethnically diverse population of pregnant women, 1999-2005". Diabetes Care 31 (5): 899–904. doi:10.2337/dc07-2345. PMID 18223030. 
17. ^ ^{a b} World Health Organisation Department of Noncommunicable Disease Surveillance (1999). "Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications" (PDF). http://whqlibdoc.who.int/hq/1999/WHO_NCD_NCS_99.2.pdf. 
18. ^ Lyssenko V, Jonsson A, Almgren P, et al. (November 2008). "Clinical risk factors, DNA variants, and the development of type 2 diabetes". N. Engl. J. Med. 359 (21): 2220–32. doi:10.1056/NEJMoa0801869. PMID 19020324. 
19. ^ Walley AJ, Blakemore AI, Froguel P (2006). "Genetics of obesity and the prediction of risk for health". Hum. Mol. Genet. 15 (Spec No 2): R124–30. doi:10.1093/hmg/ddl215. PMID 16987875. 
20. ^ "Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-onset Diabetes of the Young". National Diabetes Information Clearinghouse (NDIC) (National Institute of Diabetes and Digestive and Kidney Diseases, NIH). http://www.diabetes.niddk.nih.gov/dm/pubs/mody/. Retrieved on 2008-08-04. 
21. ^ Barrett TG (2001). "Mitochondrial diabetes, DIDMOAD and other inherited diabetes syndromes". Best Pract. Res. Clin. Endocrinol. Metab. 15 (3): 325–43. doi:10.1053/beem.2001.0149. PMID 11554774. 
22. ^ Saydah SH, Miret M, Sung J, Varas C, Gause D, Brancati FL (2001). "Postchallenge hyperglycemia and mortality in a national sample of U.S. adults". Diabetes Care 24 (8): 1397–402. PMID 11473076. 
23. ^ Santaguida PL, Balion C, Hunt D, Morrison K, Gerstein H, Raina P, Booker L, Yazdi H. "Diagnosis, Prognosis, and Treatment of Impaired Glucose Tolerance and Impaired Fasting Glucose". Summary of Evidence Report/Technology Assessment, No. 128. Agency for Healthcare Research and Quality. http://www.ahrq.gov/clinic/epcsums/impglusum.htm. Retrieved on 2008-07-20. 
24. ^ Genuth S (Jan-Feb 2006). "Insights from the diabetes control and complications trial/epidemiology of diabetes interventions and complications study on the use of intensive glycemic treatment to reduce the risk of complications of type 1 diabetes". Endocr Pract 12 (Suppl 1): 34–41. ISSN 1530-891X. PMID 16627378. 
25. ^ Lee CM, Huxley RR, Lam TH, Martiniuk AL, Ueshema H, Pan WH, Welborn T, Woodward M; Asia Pacific Cohort Studies Collaboration (2007). "Prevalence of diabetes mellitus and population attributable fractions for coronary heart disease and stroke mortality in the WHO South-East Asia and Western Pacific regions". Asia Pac J Clin Nutr 16 (1): 187–92. PMID 17215197. 
26. ^ Seidell JC (2000). "Obesity, insulin resistance and diabetes--a worldwide epidemic". Br. J. Nutr. 83 Suppl 1: S5–8. PMID 10889785. 
27. ^ Daneman D (2006). "Type 1 diabetes". Lancet 367 (9513): 847–58. doi:10.1016/S0140-6736(06)68341-4. PMID 16530579. 
28. ^ Borch-Johnsen K, Joner G, Mandrup-Poulsen T, Christy M, Zachau-Christiansen B, Kastrup K, Nerup J (1984). "Relation between breast-feeding and incidence rates of insulin-dependent diabetes mellitus. A hypothesis". Lancet 2 (8411): 1083–6. doi:10.1016/S0140-6736(84)91517-4. PMID 6150150. 
29. ^ Naim Shehadeh, Raanan Shamir, Moshe Berant, Amos Etzioni (2001). "Insulin in human milk and the prevention of type 1 diabetes". Pediatric Diabetes 2 (4): 175–7. doi:10.1034/j.1399-5448.2001.20406.x. http://www.blackwell-synergy.com/doi/abs/10.1034/j.1399-5448.2001.20406.x?journalCode=pdi. 
30. ^ Virtanen S, Knip M (2003). "Nutritional risk predictors of beta cell autoimmunity and type 1 diabetes at a young age". Am J Clin Nutr 78 (6): 1053–67. PMID 14668264. 
31. ^ Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM (2001). "Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study". Lancet 358: 1500. doi:10.1016/S0140-6736(01)06580-1. PMID 11705562. 
32. ^ Elliott RB, Pilcher CC, Fergusson DM, Stewart AW (Sep-Oct 1996). "A population based strategy to prevent insulin-dependent diabetes using nicotinamide". J. Pediatr. Endocrinol. Metab. 9 (5): 501–9. PMID 8961125. 
33. ^ Lindström J, Ilanne-Parikka P, Peltonen M, Aunola S, Eriksson J, Hemiö K, Hämäläinen H, Härkönen P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Mannelin M, Paturi M, Sundvall J, Valle T, Uusitupa M, Tuomilehto J (2006). "Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study". Lancet 368 (9548): 1673–9. doi:10.1016/S0140-6736(06)69701-8. PMID 17098085. 
34. ^ ^{a b} Knowler W, Barrett-Connor E, Fowler S, Hamman R, Lachin J, Walker E, Nathan D (2002). "Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin". N Engl J Med 346 (6): 393–403. doi:10.1056/NEJMoa012512. PMID 11832527. 
35. ^ Bantle JP, Wylie-Rosett J, Albright AL, et al. (2006). "Nutrition recommendations and interventions for diabetes--2006: a position statement of the American Diabetes Association". Diabetes Care 29 (9): 2140–57. doi:10.2337/dc06-9914. PMID 16936169. http://care.diabetesjournals.org/cgi/content/full/29/9/2140. 
36. ^ Gerstein H, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, Hanefeld M, Hoogwerf B, Laakso M, Mohan V, Shaw J, Zinman B, Holman R (2006). "Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial". Lancet 368 (9541): 1096–105. doi:10.1016/S0140-6736(06)69420-8. PMID 16997664. 
37. ^ Kjeldsen SE, Julius S, Mancia G, McInnes GT, Hua T, Weber MA, Coca A, Ekman S, Girerd X, Jamerson K, Larochelle P, Macdonald TM, Schmieder RE, Schork MA, Stolt P, Viskoper R, Widimsky J, Zanchetti A; for the VALUE Trial Investigators (2006). "Effects of valsartan compared to amlodipine on preventing type 2 diabetes in high-risk hypertensive patients: the VALUE trial". J Hypertens 24 (7): 1405–12. doi:10.1097/01.hjh.0000234122.55895.5b. PMID 16794491. 
38. ^ Wasko MC, Hubert HB, Lingala VB, et al. (2007). "Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis". JAMA 298 (2): 187–93. doi:10.1001/jama.298.2.187. PMID 17622600. 
39. ^ Stuebe AM, Rich-Edwards JW, Willett WC, Manson JE, Michels KB (2005). "Duration of lactation and incidence of type 2 diabetes". JAMA 294 (20): 2601–10. doi:10.1001/jama.294.20.2601. PMID 16304074. 
40. ^ Adler, A.I.; Stratton, I. M.; Neil, H.A.; et al. (2000). "Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study". BMJ 321 (7258): 412–9. doi:10.1136/bmj.321.7258.412. PMID 10938049. 
41. ^ ^{a b c} Vinik AI, Fishwick DT, Pittenger G (2004). "Advances in diabetes for the millennium: toward a cure for diabetes". MedGenMed : Medscape general medicine 6 (3 Suppl): 12. PMID 15647717. 
42. ^ "Pancreas transplantation for diabetes mellitus: a guide to recipient selection and optimum immunosuppression". BioDrugs. 10 (5): 347–57. 1998. PMID 18020607. 
43. ^ Shapiro AM, Ricordi C, Hering BJ, et al. (2006). "International trial of the Edmonton protocol for islet transplantation". N. Engl. J. Med. 355 (13): 1318–30. doi:10.1056/NEJMoa061267. PMID 17005949. 
44. ^ Couri CE, Oliveira MC, Stracieri AB, et al. (April 2009). "C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus". JAMA 301 (15): 1573–9. doi:10.1001/jama.2009.470. PMID 19366777. 
45. ^ Rubino, F; Gagner M (2002). "Potential of surgery for curing type 2 diabetes mellitus". Ann. Surg. 236 (5): 554–9. doi:10.1097/00000658-200211000-00003. PMID 12409659. 
46. ^ Adams, TD; Gress RE, Smith SC, et al. (2007). "Long-term mortality after gastric bypass surgery". N. Engl. J. Med. 357 (8): 753–61. doi:10.1056/NEJMoa066603. PMID 17715409. 
47. ^ Cohen, RV; Schiavon CA, Pinheiro JS, Correa JL, Rubino F (2007). "Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22-34 kg/m2: a report of 2 cases". Surg Obes Relat Dis. 3 (2): 195–7. doi:10.1016/j.soard.2007.01.009. PMID 17386401. 
48. ^ Vasonconcelos, Alberto (2007-09-01). Could type 2 diabetes be reversed using surgery?. pp. 11–3. http://www.newscientist.com/channel/health/mg19526193.100-could-type-2-diabetes-be-reversed-using-surgery.html. Retrieved on 2007-09-26. 
49. ^ Nathan, D.M.; Cleary P.A., Backlund J.Y., et al. (2005). "Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes". N. Engl. J. Med. 353 (25): 2643–53. doi:10.1056/NEJMoa052187. PMID 16371630. 
50. ^ The Diabetes Control and Complications Trial Research Group (15 April 1995). "The effect of intensive diabetes therapy on the development and progression of neuropathy. The Diabetes Control and Complications Trial Research Group". Ann. Intern. Med. 122 (8): 561–8. PMID 7887548. http://www.annals.org/cgi/pmidlookup?view=long&pmid=7887548. 
51. ^ "Women with high BP at three-fold risk of developing diabetes." TopNews.in July 1, 2009. http://www.topnews.in/women-high-bp-three-fold-risk-developing-diabetes-23341
52. ^ ^{a b} Harris MI, Flegal KM, Cowie CC, et al. (1998). "Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994". Diabetes Care 21 (4): 518–24. doi:10.2337/diacare.21.4.518. PMID 9571335. 
53. ^ Chang AM, Halter JB (January 2003). "Aging and insulin secretion". Am. J. Physiol. Endocrinol. Metab. 284 (1): E7–12. doi:10.1152/ajpendo.00366.2002. PMID 12485807. http://ajpendo.physiology.org/cgi/content/full/284/1/E7?ck=nck. 
54. ^ "Diabetes and Aging". Diabetes Dateline. National Institute of Diabetes and Digestive and Kidney Diseases. 2002. http://diabetes.niddk.nih.gov/about/dateline/spri02/8.htm. Retrieved on 2007-05-14. 
55. ^ Weiss J, Sumpio B (2006). "Review of prevalence and outcome of vascular disease in patients with diabetes mellitus". Eur J Vasc Endovasc Surg 31 (2): 143–50. doi:10.1016/j.ejvs.2005.08.015. PMID 16203161. 
56. ^ Aristides Veves, Rayaz A. Malik (2007). Diabetic Neuropathy: Clinical Management (Clinical Diabetes), Second Edition. New York: Humana Press. pp. 188–198. ISBN 1-58-829626-1. 
57. ^ Gispen WH, Biessels GJ (November 2000). "Cognition and synaptic plasticity in diabetes mellitus". Trends Neurosci. 23 (11): 542–9. doi:10.1016/S0166-2236(00)01656-8. PMID 11074263. 
58. ^ ^{a b c d} Wild S, Roglic G, Green A, Sicree R, King H (May 2004). "Global prevalence of diabetes: estimates for the year 2000 and projections for 2030". Diabetes Care 27 (5): 1047–53. doi:10.2337/diacare.27.5.1047. PMID 15111519. http://care.diabetesjournals.org/cgi/content/full/27/5/1047. 
59. ^ http://www.cdc.gov/Features/diabetesfactsheet/
60. ^ "CDC's Diabetes Program-News and Information-Press Releases-October 26 2000". http://www.cdc.gov/Diabetes/news/docs/010126.htm. Retrieved on 2008-06-23. 
61. ^ Narayan K, Boyle J, Thompson T, Sorensen S, Williamson D (2003). "Lifetime risk for diabetes mellitus in the United States". JAMA 290 (14): 1884–90. doi:10.1001/jama.290.14.1884. PMID 14532317. 
62. ^ American Diabetes Association (2005). "Total Prevalence of Diabetes & Pre-diabetes". http://www.diabetes.org/diabetes-statistics/prevalence.jsp. Retrieved on 2006-03-17. 
63. ^ "Seniors and Diabetes". Elderly And Diabetes-Diabetes and Seniors. LifeMed Media. 2006. http://www.dlife.com/dLife/do/ShowContent/daily_living/seniors/. Retrieved on 2007-05-14. 
64. ^ Australian Institute for Health and Welfare. "Diabetes, an overview". http://www.aihw.gov.au/indigenous/health/diabetes.cfm. Retrieved on 2008-06-23. 
65. ^ Dobson, M. (1776). "Nature of the urine in diabetes". Medical Observations and Inquiries 5: 298–310. 
66. ^ Medvei, Victor Cornelius (1993). The history of clinical endocrinology. Carnforth, Lancs., U.K: Parthenon Pub. Group. pp. 23–34. ISBN 1-85070-427-9. 
67. ^ ^{a b} Dwivedi, Girish & Dwivedi, Shridhar (2007). History of Medicine: Sushruta – the Clinician – Teacher par Excellence. National Informatics Centre (Government of India).
68. ^ Nabipour, I. (2003), "Clinical Endocrinology in the Islamic Civilization in Iran", International Journal of Endocrinology and Metabolism 1: 43–45 [44–5] 
69. ^ ^{a b c} Patlak M (2002). "New weapons to combat an ancient disease: treating diabetes". Faseb J 16 (14): 1853. doi:10.1096/fj.02-0974bkt. PMID 12468446. http://www.fasebj.org/cgi/content/full/16/14/1853e. 
70. ^ Von Mehring J, Minkowski O. (1890). "Diabetes mellitus nach pankreasexstirpation". Arch Exp Pathol Pharmakol 26: 371–387. doi:10.1007/BF01831214. 
71. ^ Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA (01 January 1922). "Pancreatic extracts in the treatment of diabetes mellitus". Canad Med Assoc J 12 (10): 141–6. PMID 1933711. 
72. ^ Himsworth (1936). "Diabetes mellitus: its differentiation into insulin-sensitive and insulin-insensitive types". Lancet i: 127–30. doi:10.1016/S0140-6736(01)36134-2. 
73. ^ Department of Health (Malta), 1897–1972:Annual Reports.
74. ^ Yalow RS, Berson SA (1960). "Immunoassay of endogenous plasma insulin in man". J. Clin. Invest. 39: 1157–75. doi:10.1172/JCI104130. PMID 13846364. 
75. ^ The Diabetes Control And Complications Trial Research Group, (1993). "The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group". N Engl J Med 329 (14): 977–86. doi:10.1056/NEJM199309303291401. PMID 8366922. 
76. ^ Theodore H. Tulchinsky, Elena A. Varavikova (2008). The New Public Health, Second Edition. New York: Academic Press. p. 200. ISBN 0-12-370890-7. 
77. ^ Piwernetz K, Home PD, Snorgaard O, Antsiferov M, Staehr-Johansen K, Krans M. (1993). "Monitoring the targets of the St Vincent Declaration and the implementation of quality management in diabetes care: the DIABCARE initiative. The DIABCARE Monitoring Group of the St Vincent Declaration Steering Committee.". Diabet Med. 10 (4): 303–4. PMID 8508624. 
78. ^ Dubois, HFW and Bankauskaite, V (2005). "Type 2 diabetes programmes in Europe" (PDF). Euro Observer 7 (2): 5–6. http://www.euro.who.int/Document/Obs/EuroObserver7_3.pdf. 
79. ^ Stewart WF, Ricci JA, Chee E, Hirsch AG, Brandenburg NA. "Lost productive time and costs due to diabetes and diabetic neuropathic pain in the US workforce." J. Occup. Environ. Med. Vol. 49, No. 6, 672-679, 2007.

External links

• Diabetesat the Open Directory Project
• American Diabetes Association
• National Diabetes Education Program

v • d • e Endocrine pathology: endocrine diseases (E00-35, 240-259) Pancreas/ glucose metabolism Hypofunction Diabetes mellitus types: (type 1, type 2, MODY 1 2 3 4 5) · complications (coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy, cardiomyopathy) insulin receptor (Rabson-Mendenhall syndrome) · Insulin resistance Hyperfunction Hypoglycemia · Hyperinsulinism · Zollinger-Ellison syndrome Hypothalamic/ pituitary axes Hypothalamus gonadotropin (Kallmann syndrome, Adiposogenital dystrophy) · CRH (Tertiary adrenal insufficiency) · vasopressin (Neurogenic diabetes insipidus) · general (Hypothalamic hamartoma) Pituitary Hyperpituitarism anterior (Acromegaly, Hyperprolactinaemia, Pituitary ACTH hypersecretion) · posterior (SIADH) · general (Nelson's syndrome) Hypopituitarism anterior (Kallmann syndrome, Growth hormone deficiency, ACTH deficiency/Secondary adrenal insufficiency) · posterior (Neurogenic diabetes insipidus) · general (Empty sella syndrome, Pituitary apoplexy, Sheehan's syndrome, Lymphocytic hypophysitis) Thyroid Hypothyroidism Iodine deficiency · Cretinism (Congenital hypothyroidism) · Myxedema · Euthyroid sick syndrome Hyperthyroidism Hyperthyroxinemia (Thyroid hormone resistance, Familial dysalbuminemic hyperthyroxinemia) · Hashitoxicosis · Thyrotoxicosis factitia · Graves' disease Thyroiditis Acute infectious · Subacute (De Quervain's, Subacute lymphocytic) · Autoimmune/chronic (Hashimoto's, Postpartum, Riedel's) Goitre Endemic goitre · Toxic nodular goitre · Toxic multinodular goitre Thyroid nodule Parathyroid Hypoparathyroidism Pseudohypoparathyroidism Hyperparathyroidism Primary · Secondary · Tertiary · Osteitis fibrosa cystica Adrenal Hyperfunction aldosterone: Hyperaldosteronism/Primary aldosteronism (Conn syndrome, Bartter syndrome, Glucocorticoid remediable aldosteronism) · AME · Liddle's syndrome · 17α CAH cortisol: Cushing's syndrome (Pseudo-Cushing's syndrome) sex hormones: 21α CAH · 11β CAH Hypofunction/ Adrenal insufficiency (Addison's, WF) aldosterone: Hypoaldosteronism (21α CAH, 11β CAH) cortisol: CAH (Lipoid, 3β, 11β, 17α, 21α) sex hormones: 17α CAH Gonads ovarian (Polycystic ovary syndrome, Premature ovarian failure) testicular (5-alpha-reductase deficiency, 17-beta-hydroxysteroid dehydrogenase deficiency) · Androgen receptor (Androgen insensitivity syndrome) general (Hypogonadism, Delayed puberty, Precocious puberty) Height Gigantism · Dwarfism/Short stature (Laron syndrome, Psychogenic dwarfism) Multiple Autoimmune polyendocrine syndrome (APS1, APS2) · Carcinoid syndrome · Multiple endocrine neoplasia (1, 2A, 2B) · Progeria · Woodhouse-Sakati syndrome see also congenital, neoplasia

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