A chronic metabolic disorder marked by hyperglycemia. DM results either from failure of the pancreas to produce insulin (type 1 DM) or from insulin resistance, with inadequate insulin secretion to sustain normal metabolism (type 2 DM). Either type of DM may damage blood vessels, nerves, kidneys, the retina, and the developing fetus and the placenta during pregnancy. Type 1 or insulin-dependent DM has a prevalence of just 0.3 to 0.4%. Type 2 DM (formerly called adult-onset DM) has a prevalence in the general population of 6.6%. In some populations (such as older persons, Native Americans, African Americans, Pacific Islanders, Mexican Americans), it is present in nearly 20% of adults. Type 2 DM primarily affects obese middle-aged people with sedentary lifestyles, whereas type 1 DM usually occurs in children, most of whom are active and thin, although extremely obese children are now being diagnosed with type 2 diabetes as well. See: table; dawn phenomenon; insulin; insulin pump; insulin resistance; diabetic polyneuropathy; Somogyi phenomenon
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.
a complex disorder of carbohydrate, fat, and protein metabolism that is primarily a result of a deficiency or complete lack of insulin secretion by the beta cells of the pancreas or resistance to insulin. The disease is often familial but may be acquired, as in Cushing's syndrome, as a result of the administration of excessive glucocorticoid. The various forms of diabetes have been organized into categories developed by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Diabetes Association. Type 1 diabetes mellitus in this classification scheme includes patients with diabetes caused by an autoimmune process, dependent on insulin to prevent ketosis. This group was previously called type I, insulin-dependent diabetes mellitus, juvenile-onset diabetes, brittle diabetes, or ketosis-prone diabetes. Patients with type 2 diabetes mellitus are those previously designated as having type II, non-insulin-dependent diabetes mellitus, maturity-onset diabetes, adult-onset diabetes, ketosis-resistant diabetes, or stable diabetes. Those with gestational diabetes mellitus are women in whom glucose intolerance develops during pregnancy. Other types of diabetes are associated with a pancreatic disease, hormonal changes, adverse effects of drugs, or genetic or other anomalies. A fourth subclass, the impaired glucose tolerance group, also called prediabetes, includes persons whose blood glucose levels are abnormal although not sufficiently above the normal range to be diagnosed as having diabetes. Approximately 95% of the 18 million diabetes patients in the United States are classified as type 2, and more than 70% of those patients are obese. About 1.3 million new cases of diabetes mellitus are diagnosed in the United States each year. Contributing factors to the development of diabetes are heredity; obesity; sedentary life-style; high-fat, low-fiber diets; hypertension; and aging. See also impaired glucose tolerance, potential abnormality of glucose tolerance, previous abnormality of glucose tolerance.

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 also are more likely to develop Type II diabetes than those who remain in their original countries.
Nephrogenic diabetes insipidus. In some cases, nephrogenic diabetes insipidus goes away after treatment of the cause. For example, switching medications or taking steps to balance the amount of calcium or potassium in the patient’s body may resolve the problem. Medications for nephrogenic diabetes insipidus include diuretics, either alone or combined with aspirin or ibuprofen. Health care providers commonly prescribe diuretics to help patients’ kidneys remove fluid from the body. Paradoxically, in people with nephrogenic diabetes insipidus, a class of diuretics called thiazides reduces urine production and helps patients’ kidneys concentrate urine. Aspirin or ibuprofen also helps reduce urine volume.
The earliest surviving work with a detailed reference to diabetes is that of Aretaeus of Cappadocia (2nd or early 3rd century CE). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness, reflecting the beliefs of the "Pneumatic School". He hypothesized a correlation between diabetes and other diseases, and he discussed differential diagnosis from the snakebite, which also provokes excessive thirst. His work remained unknown in the West until 1552, when the first Latin edition was published in Venice.[113]
The classic symptoms of untreated diabetes are unintended weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger).[22] Symptoms may develop rapidly (weeks or months) in type 1 diabetes, while they usually develop much more slowly and may be subtle or absent in type 2 diabetes. Other symptoms of diabetes include weight loss and tiredness.[23]
Type 1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors,[42] such as a viral infection or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans.[42][43] Among dietary factors, data suggest that gliadin (a protein present in gluten) may play a role in the development of type 1 diabetes, but the mechanism is not fully understood.[44][45]

The protocol for therapy is determined by the type of diabetes; patients with either type 1 or type 2 must pay attention to their diet and exercise regimens. Insulin therapy may be prescribed for patients with type 2 diabetes as well as any who are dependent on insulin. In most cases, the type 2 diabetes patient can be treated effectively by reducing caloric intake, maintaining target weight, and promoting physical exercise.
This type of DI occurs only during pregnancy when an enzyme made by the placenta destroys a mother’s ADH. It may also be caused by an increased level of a hormone-like chemical that makes the kidneys less sensitive to ADH. The placenta plays an important role in the exchange of nutrients and waste products between the fetus and the mother. The condition should resolve after pregnancy.
A person's body regulates fluid by balancing liquid intake and removing extra fluid. Thirst usually controls a person’s rate of liquid intake, while urination removes most fluid, although people also lose fluid through sweating, breathing, or diarrhea. The hormone vasopressin, also called antidiuretic hormone, controls the fluid removal rate through urination. The hypothalamus, a small gland located at the base of the brain, produces vasopressin. The nearby pituitary gland stores the vasopressin and releases it into the bloodstream when the body has a low fluid level. Vasopressin signals the kidneys to absorb less fluid from the bloodstream, resulting in less urine. When the body has extra fluid, the pituitary gland releases smaller amounts of vasopressin, and sometimes none, so the kidneys remove more fluid from the bloodstream and produce more urine.
The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Apollonius of Memphis.[111] The disease was considered rare during the time of the Roman empire, with Galen commenting he had only seen two cases during his career.[111] This is possibly due to the diet and lifestyle of the ancients, or because the clinical symptoms were observed during the advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea urinosa).[113]
Gestational diabetes insipidus. You can only get this type during pregnancy. Sometimes the placenta -- the organ that gives oxygen and nutrients to your baby -- creates an enzyme that breaks down the mother's vasopressin. And some pregnant women make more prostaglandin, a hormone-like chemical that makes their kidneys less sensitive to vasopressin. Most cases of gestational diabetes insipidus are mild and don’t cause noticeable symptoms. The condition usually goes away after birth, but it might come back during another pregnancy.
About Diabetes, Type 2:  Type 2 diabetes is characterized by "insulin resistance" as body cells do not respond appropriately when insulin is present. This is a more complex problem than type 1, but is sometimes easier to treat, since insulin is still produced, especially in the initial years. Type 2 may go unnoticed for years in a patient before diagnosis, since the symptoms are typically milder (no ketoacidosis) and can be sporadic. However, severe complications can result from unnoticed type 2 diabetes, including renal failure, and coronary artery disease. Type 2 diabetes was formerly known by a variety of partially misleading names, including "adult-onset diabetes", "obesity-related diabetes", "insulin-resistant diabetes", or "non-insulin-dependent diabetes" (NIDDM). It may be caused by a number of diseases, such as hemochromatosis and polycystic ovary syndrome, and can also be caused by certain types of medications (e.g. long-term steroid use). About 90-95% of all North American cases of diabetes are type 2, and about 20% of the population over the age of 65 is a type 2 diabetic. The fraction of type 2 diabetics in other parts of the world varies substantially, almost certainly for environmental and lifestyle reasons. There is also a strong inheritable genetic connection in type 2 diabetes: having relatives (especially first degree) with type 2 is a considerable risk factor for developing type 2 diabetes. The majority of patients with type 2 diabetes mellitus are obese - chronic obesity leads to increased insulin resistance that can develop into diabetes, most likely because adipose tissue is a (recently identified) source of chemical signals (hormones and cytokines).
People with diabetes can benefit from education about the disease and treatment, good nutrition to achieve a normal body weight, and exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.[83][84]
The classic symptoms of untreated diabetes are unintended weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger).[22] Symptoms may develop rapidly (weeks or months) in type 1 diabetes, while they usually develop much more slowly and may be subtle or absent in type 2 diabetes. Other symptoms of diabetes include weight loss and tiredness.[23]
Purified human insulin is most commonly used, however, insulin from beef and pork sources also are 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. The small battery-operated pump is worn outside the body and is connected to a needle that is inserted into the abdomen. Pumps can be programmed to inject small doses of insulin at various times during the day, or the patient may be able to adjust the insulin doses to coincide with meals and exercise.
In type 2 diabetes (adult onset diabetes), the pancreas makes insulin, but it either doesn't produce enough, or the insulin does not work properly. Nine out of 10 people with diabetes have type 2. This type occurs most often in people who are over 40 years old but can occur even in childhood if there are risk factors present. Type 2 diabetes may sometimes be controlled with a combination of diet, weight management and exercise. However, treatment also may include oral glucose-lowering medications (taken by mouth) or insulin injections (shots).
^ Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, Rosenson RS, Williams CD, Wilson PW, Kirkman MS (June 2010). "Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation". Diabetes Care. 33 (6): 1395–402. doi:10.2337/dc10-0555. PMC 2875463. PMID 20508233.
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, the immune system, the body's defense system against infection, is believed to be triggered by a virus or another microorganism that destroys cells in the pancreas that produce insulin. In Type II diabetes, age, obesity, and family history of diabetes play a role.
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 during the day to keep the blood sugar level within a fairly normal range.
Some patients with type 2 DM can control their disease with a calorically restricted diet (for instance 1600 to 1800 cal/day), regular aerobic exercise, and weight loss. Most patients, however, require the addition of some form of oral hypoglycemic drug or insulin. Oral agents to control DM include sulfonylurea drugs (such as glipizide), which increase pancreatic secretion of insulin; biguanides or thiazolidinediones (such as metformin or pioglitazone), which increase cellular sensitivity to insulin; or a-glucosidase inhibitors (such as acarbose), which decrease the absorption of carbohydrates from the gastrointestinal tract. Both types of diabetics also may be prescribed pramlintide (Symlin), a synthetic analog of human amylin, a hormone manufactured in the pancreatic beta cells. It enhances postprandial glucose control by slowing gastric emptying, decreasing postprandial glucagon concentrations, and regulating appetite and food intake; thus pramlintide is helpful for patients who do not achieve optimal glucose control with insulin and/or oral antidiabetic agents. When combinations of these agents fail to normalize blood glucose levels, insulin injections are added. Tight glucose control can reduce the patient’s risk of many of the complications of the disease. See: illustration

Medications in this drug class may reduce the risk of heart attack and stroke in people with a high risk of those conditions. Side effects may include vaginal yeast infections, urinary tract infections, low blood pressure, and a higher risk of diabetic ketoacidosis. Canagliflozin, but not the other drugs in the class, has been associated with increased risk of lower limb amputation.
Medications used to treat diabetes do so by lowering blood sugar levels. There is broad consensus that when people with diabetes maintain tight glucose control (also called "tight glycemic control") – keeping the glucose levels in their blood within normal ranges – that they experience fewer complications like kidney problems and eye problems.[87][88] There is however debate as to whether this is cost effective for people later in life.[89]
Prevention and treatment involve maintaining a healthy diet, regular physical exercise, a normal body weight, and avoiding use of tobacco.[2] Control of blood pressure and maintaining proper foot care are important for people with the disease.[2] Type 1 diabetes must be managed with insulin injections.[2] Type 2 diabetes may be treated with medications with or without insulin.[13] Insulin and some oral medications can cause low blood sugar.[14] Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 diabetes.[15] Gestational diabetes usually resolves after the birth of the baby.[16]
Exercise. A program of regular exercise gives anyone a sense of good health and well-being; for persons with diabetes it gives added benefits by helping to control blood glucose levels, promoting circulation to peripheral tissues, and strengthening the heart beat. In addition, there is evidence that exercise increases the number of insulin receptor sites on the surface of cells and thus facilitates the metabolism of glucose. Many specialists in diabetes consider exercise so important in the management of diabetes that they prescribe rather than suggest exercise.
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 usually can 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.
FASTING GLUCOSE TEST. Blood is drawn from a vein in the patient's arm after a period at least eight hours when the patient has not eaten, 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. 

A short form of the deprivation test. A health care provider instructs the patient to stop drinking all liquids for a specific period of time, usually during dinner. The next morning, the patient will collect a urine sample at home. The patient then returns the urine sample to his or her health care provider or takes it to a lab where a technician measures the concentration of the urine sample.

Type 1 diabetes occurs because the insulin-producing cells of the pancreas (beta cells) are damaged. In type 1 diabetes, the pancreas makes little or no insulin, so sugar cannot get into the body's cells for use as energy. People with type 1 diabetes must use insulin injections to control their blood glucose. Type 1 is the most common form of diabetes in people who are under age 30, but it can occur at any age. Ten percent of people with diabetes are diagnosed with type 1.


Your urinary system — which includes the kidneys, ureters, bladder and urethra — is responsible for removing waste from your body through urine. Your kidneys, located toward the back in your upper abdomen, produce urine by filtering waste and fluid from your blood. That urine then travels through your ureters to your bladder, where the urine is stored until you can eliminate it at an appropriate time.
Diabetes is a chronic disease, for which there is no known cure except in very specific situations.[78] Management concentrates on keeping blood sugar levels as close to normal, without causing low blood sugar. This can usually be accomplished with a healthy diet, exercise, weight loss, and use of appropriate medications (insulin in the case of type 1 diabetes; oral medications, as well as possibly insulin, in type 2 diabetes).
Diabetes is suspected based on symptoms. Urine tests and blood tests can be used to confirm a diagnose of diabetes based on the amount of glucose found. Urine can also detect ketones and protein in the urine that 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 on a standardized diet, oral medications, or insulin.
^ Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, Rosenson RS, Williams CD, Wilson PW, Kirkman MS (June 2010). "Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation". Diabetes Care. 33 (6): 1395–402. doi:10.2337/dc10-0555. PMC 2875463. PMID 20508233.
Regular insulin is fast-acting and starts to work within 15-30 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 18-26 hours. Ultra-lente is a long-acting form of insulin that starts to work within four to eight hours and lasts 28-36 hours.
People with diabetes can benefit from education about the disease and treatment, good nutrition to achieve a normal body weight, and exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.[83][84]

Recently, battery-operated insulin pumps have been developed that can be programmed to mimic normal insulin secretion more closely. A person wearing an insulin pump still must monitor blood sugar several times a day and adjust the dosage, and not all diabetic patients are motivated or suited to such vigilance. It is hoped that in the future an implantable or external pump system may be perfected, containing a glucose sensor. In response to data from the sensor the pump will automatically deliver insulin according to changing levels of blood glucose.

Exercise. A program of regular exercise gives anyone a sense of good health and well-being; for persons with diabetes it gives added benefits by helping to control blood glucose levels, promoting circulation to peripheral tissues, and strengthening the heart beat. In addition, there is evidence that exercise increases the number of insulin receptor sites on the surface of cells and thus facilitates the metabolism of glucose. Many specialists in diabetes consider exercise so important in the management of diabetes that they prescribe rather than suggest exercise.
Desmopressin will be ineffective in nephrogenic DI which is treated by reversing the underlying cause (if possible) and replacing the free water deficit. A thiazide diuretic, such as chlorthalidone or hydrochlorothiazide, can be used to create mild hypovolemia which encourages salt and water uptake in proximal tubule and thus improve nephrogenic diabetes insipidus.[14] Amiloride has additional benefit of blocking Na uptake. Thiazide diuretics are sometimes combined with amiloride to prevent hypokalemia caused by the thiazides. It seems paradoxical to treat an extreme diuresis with a diuretic, and the exact mechanism of action is unknown but the thiazide diuretics will decrease distal convoluted tubule reabsorption of sodium and water, thereby causing diuresis. This decreases plasma volume, thus lowering the glomerular filtration rate and enhancing the absorption of sodium and water in the proximal nephron. Less fluid reaches the distal nephron, so overall fluid conservation is obtained.[15]

^ Kyu HH, Bachman VF, Alexander LT, Mumford JE, Afshin A, Estep K, Veerman JL, Delwiche K, Iannarone ML, Moyer ML, Cercy K, Vos T, Murray CJ, Forouzanfar MH (August 2016). "Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013". BMJ. 354: i3857. doi:10.1136/bmj.i3857. PMC 4979358. PMID 27510511.


The main effector organ for fluid homeostasis is the kidney. ADH acts by increasing water permeability in the collecting ducts and distal convoluted tubules; specifically, it acts on proteins called aquaporins and more specifically aquaporin 2 in the following cascade. When released, ADH binds to V2 G-protein coupled receptors within the distal convoluted tubules, increasing cyclic AMP, which couples with protein kinase A, stimulating translocation of the aquaporin 2 channel stored in the cytoplasm of the distal convoluted tubules and collecting ducts into the apical membrane. These transcribed channels allow water into the collecting duct cells. The increase in permeability allows for reabsorption of water into the bloodstream, thus concentrating the urine.
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