Diabetes mellitus, often simply referred to as diabetes—is a condition in which a person has high blood sugar The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally, in mammals the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM (mmol/L, ie, millimoles/liter). It is tightly regulated as a part of metabolic homeostasis, either because the body does not produce enough insulin Insulin is a hormone that is central to regulate energy and glucose metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle, or because cells do not respond to the insulin that is produced. This high blood sugar produces the classical symptoms of polyuria In medicine, polyuria is a condition usually defined as excessive or abnormally large production and/or passage of urine . Frequent urination is sometimes included by definition, but is in any case a usual complication. Increased production and passage of urine may also be termed diuresis (frequent urination), polydipsia Polydipsia is a medical symptom in which the patient displays excessive thirst. The word derives from the Greek πολυδιψία, which is derived from πολύς + δίψα (dipsa, "thirst"). An etymologically related term is dipsomaniac, meaning an alcoholic (increased thirst) and polyphagia In medicine, polyphagia is a medical sign meaning excessive hunger and abnormally large intake of solids by mouth (increased hunger).

There are three main types of diabetes:

• Type 1 diabetes Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms of polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and: results from the body's failure to produce insulin, and presently requires the person to inject insulin.
• Type 2 diabetes Diabetes mellitus type 2 or type 2 diabetes (formerly called non -insulin-dependent diabetes mellitus , or adult-onset diabetes) is a disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and dietary modification. As the: results from insulin resistance Insulin resistance is a physiological condition where the natural hormone, insulin, becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects. Certain cell types such as fat and muscle cells require insulin to absorb glucose. When these cells, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency.
• Gestational diabetes Gestational diabetes is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy: is when pregnant women, who have never had diabetes before, have a high blood glucose level during pregnancy. It may precede development of type 2 DM.

Other forms of diabetes mellitus include congenital diabetes, which is due to genetic defects of insulin secretion, cystic fibrosis-related diabetes, steroid diabetes induced by high doses of glucocorticoids, and several forms of monogenic diabetes Maturity onset diabetes of the young refers to any of several hereditary forms of diabetes caused by mutations in an autosomal dominant gene (sex independent, i.e. inherited from any of the parents) disrupting insulin production. MODY is often referred to as "monogenic diabetes" to distinguish it from the more common types of diabetes (.

All forms of diabetes have been treatable since insulin Insulin is a hormone that is central to regulate energy and glucose metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle became available in 1921, and type 2 diabetes may be controlled with medications. Both type 1 and 2 are chronic conditions that usually cannot be cured. Pancreas transplants A pancreas transplant is an organ transplant that involves implanting a healthy pancreas into a person who usually has diabetes. Because the pancreas is a vital organ, performing functions necessary in the digestion process, the recipient's native pancreas is left in place, and the donated pancreas is attached in a different location. In the event have been tried with limited success in type 1 DM; gastric bypass surgery Gastric bypass procedures are any of a group of similar operations used to treat morbid obesity—the severe accumulation of excess weight as fatty tissue—and the health problems (comorbidities) it causes. Bariatric surgery is the term encompassing all of the surgical treatments for morbid obesity, not just gastric bypasses, which make up only has been successful in many with morbid obesity Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems. Body mass index , a measurement which compares weight and height, defines people as overweight (pre-obese) when their BMI is between 25 kg/m2 and 30 and type 2 DM. Gestational diabetes usually resolves after delivery. Diabetes without proper treatments can cause many complications. Acute This adjective is part of the definition of several diseases and is, therefore, incorporated in their name, for instance, severe acute respiratory syndrome, acute leukemia complications include hypoglycemia Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood" . It can produce a variety of symptoms and effects but the principal problems arise from an inadequate supply of glucose to the brain, resulting in impairment of function (, diabetic ketoacidosis Diabetic ketoacidosis is a potentially life-threatening complication in patients with diabetes mellitus. It happens predominantly in those with type 1 diabetes, but it can occur in those with type 2 diabetes under certain circumstances. DKA results from an absolute shortage of insulin; in response the body switches to burning fatty acids and, or nonketotic hyperosmolar coma Nonketotic hyperosmolar coma is a type of diabetic coma associated with a high mortality seen in diabetes mellitus type 2. The preferred term used by the American Diabetes Association is hyperosmolar nonketotic state (HNS). Other commonly used names are hyperosmolar hyperglycemic nonketotic coma (HHNKC) or hyperosmotic non-ketotic coma (HONKC). It. Serious long-term complications include cardiovascular disease Heart disease or cardiovascular diseases is the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system (as used in MeSH C14), it is usually used to refer to those related to atherosclerosis (arterial disease). These conditions have similar causes,, chronic renal failure Chronic kidney disease , also known as chronic renal disease, is a progressive loss of renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite. Often, chronic kidney disease is diagnosed as a result of screening of, retinal damage Diabetic retinopathy is retinopathy caused by complications of diabetes mellitus, which can eventually lead to blindness. It is an ocular manifestation of systemic disease which affects up to 80% of all patients who have had diabetes for 10 years or more. Despite these intimidating statistics, research indicates that at least 90% of these new. Adequate treatment of diabetes is thus important, as well as blood pressure Blood pressure is a force exerted by circulating blood on the walls of blood vessels, and is one of the principal vital signs. During each heartbeat, BP varies between a maximum (systolic) and a minimum (diastolic) pressure. The mean BP, due to pumping by the heart and resistance in blood vessels, decreases as the circulating blood moves away from control and lifestyle factors such as smoking Tobacco smoking is the practice where tobacco is burned and the vapors either tasted or inhaled. The practice began as early as 5000–3000 BC. Many civilizations burnt incense during religious rituals, which was later adopted for pleasure or as a social tool. Tobacco was introduced to the Old World in the late 1500s where it followed common trade cessation and maintaining a healthy body weight Although some people prefer the less-ambiguous term body mass, the term body weight is overwhelmingly used in daily English speech as well as in the contexts of biological and medical sciences to describe the mass of an organism's body. Body weight is measured in kilograms throughout the world, although in some countries people more often measure.

As of 2000 at least 171 million people worldwide suffer from diabetes, or 2.8% of the population.^[2] Type 2 diabetes is by far the most common, affecting 90 to 95% of the U.S. diabetes population.^[3]

Contents 1 Definition 2 Classification 2.1 Type 1 diabetes 2.2 Type 2 diabetes 2.3 Gestational diabetes 2.4 Other types 3 Signs and symptoms 4 Causes 5 Pathophysiology 6 Diagnosis 7 Management 7.1 Lifestyle modifications 7.2 Medications 7.3 Support 8 Prognosis 9 Epidemiology 10 History 11 Society and culture 12 References 13 External links

Definition

The term diabetes, without qualification, usually refers to diabetes mellitus, which roughly translates to excessive sweet urine (known as "glycosuria Glycosuria or glucosuria is the excretion of glucose into the urine. Ordinarily, urine contains no glucose because the kidneys are able to reclaim all of the filtered glucose back into the bloodstream. Glycosuria is nearly always caused by elevated blood glucose levels, most commonly due to untreated diabetes mellitus. Rarely, glycosuria is due to"). Several rare conditions are also named diabetes. The most common of these is diabetes insipidus Diabetes insipidus is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the latter. There are several different types of DI, each with a different cause. The most common type in humans is central DI, caused by a deficiency of arginine in which large amounts of urine are produced (polyuria In medicine, polyuria is a condition usually defined as excessive or abnormally large production and/or passage of urine . Frequent urination is sometimes included by definition, but is in any case a usual complication. Increased production and passage of urine may also be termed diuresis), which is not sweet (insipidus meaning "without taste" in Latin).

The term "type 1 diabetes" has 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: gestational diabetes Gestational diabetes is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy,^[4] insulin-resistant type 1 diabetes (or "double diabetes"), type 2 diabetes which has progressed to require injected insulin, and latent autoimmune diabetes Latent autoimmune diabetes of adults is a term coined by Tuomi et al. in 1993 (Diabetes 42:359-362) to describe slow-onset Type 1 autoimmune diabetes in adults. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (Diabetes Care, Volume 30, Supplement 1, January 2007) does not recognize the term LADA; rather, the Expert of adults (or LADA or "type 1.5" diabetes)^[5]

Classification

Most cases of diabetes mellitus fall into three broad categories: type 1 Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms of polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and, type 2 Diabetes mellitus type 2 or type 2 diabetes (formerly called non -insulin-dependent diabetes mellitus , or adult-onset diabetes) is a disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and dietary modification. As the, and gestational diabetes Gestational diabetes is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy. A few other types are described.

Type 1 diabetes

Main article: Diabetes mellitus type 1 Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms of polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and

Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells Beta cells are a type of cell in the pancreas in areas called the islets of Langerhans. They make up 65-80% of the cells in the islets of the islets of Langerhans The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas. There are about one million islets in a healthy adult human pancreas, which are in the pancreas leading to insulin deficiency. This type of diabetes can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, where beta cell loss is a T-cell T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and natural killer cells by the presence of a special receptor on their cell surface called T cell receptors . The abbreviation T, in T cell, mediated autoimmune Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease. Prominent examples include Coeliac disease, diabetes mellitus type 1 , systemic lupus attack.^[6] There is no known preventive measure against type 1 diabetes, which causes approximately 10% of diabetes mellitus cases in North America and Europe. 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.

Type 2 diabetes

Main article: Diabetes mellitus type 2 Diabetes mellitus type 2 or type 2 diabetes (formerly called non -insulin-dependent diabetes mellitus , or adult-onset diabetes) is a disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and dietary modification. As the

Type 2 diabetes mellitus is characterized by insulin resistance Insulin resistance is a physiological condition where the natural hormone, insulin, becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects. Certain cell types such as fat and muscle cells require insulin to absorb glucose. When these cells which may be combined with relatively reduced insulin secretion. The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor In molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. It belongs to the large class of tyrosine kinase receptors. However, the specific defects are not known. Diabetes mellitus due to a known 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. At this stage hyperglycemia can be reversed by a variety of measures and medications Anti-diabetic drugs treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the that improve insulin sensitivity or reduce glucose production by the liver The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion. The liver is necessary for survival; there is currently no way to compensate for the absence of liver function. As the disease progresses, the impairment of insulin secretion occurs, and therapeutic replacement of insulin may sometimes become necessary in certain patients.^{[citation needed]}

Gestational diabetes

Main article: Gestational diabetes Gestational diabetes is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy

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 Pregnancy is the carrying of one or more offspring, known as a fetus or embryo, inside the womb of a female. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets. Human pregnancy is the most studied of all mammalian pregnancies. Childbirth usually occurs about 38 weeks after conception; i.e., approximately 40 weeks 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 Large for gestational age babies are those whose birth weight (or length, or head circumference) lies above the 90th percentile for that gestational age. Macrosomia, also known as big baby syndrome, is sometimes used synonymously with LGA, or is otherwise defined as a fetus that weighs above 4000 grams (8 lb 13 oz) or 4500 grams (9 lb 15 oz) (high birth weight), congenital cardiac and central nervous system anomalies, and skeletal muscle malformations. Increased fetal insulin may inhibit fetal surfactant Surfactants are compounds that lower the surface tension of a liquid, allowing easier spreading, and lowering of the interfacial tension between two liquids, or between a liquid and a solid. Surfactants may act as: detergents, wetting agents, emulsifiers, foaming agents, and dispersants production and cause respiratory distress syndrome Infant respiratory distress syndrome , also called neonatal respiratory distress syndrome or respiratory distress syndrome of newborn, previously called hyaline membrane disease, is a syndrome caused in premature infants by developmental insufficiency of surfactant production and structural immaturity in the lungs. It can also result from a. Hyperbilirubinemia Jaundice, also known as icterus , is a yellowish discoloration of the skin, the conjunctival membranes over the sclerae (whites of the eyes), and other mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in the blood). This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluids 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. Labor induction may be indicated with decreased placental function. A cesarean section A Caesarian section , also known as C-section or Caesar, is a surgical procedure in which incisions are made through a mother's abdomen (laparotomy) and uterus (hysterotomy) to deliver one or more babies. It is usually performed when a vaginal delivery would put the baby's or mother's life or health at risk, although in recent times it has been may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia Large for gestational age babies are those whose birth weight (or length, or head circumference) lies above the 90th percentile for that gestational age. Macrosomia, also known as big baby syndrome, is sometimes used synonymously with LGA, or is otherwise defined as a fetus that weighs above 4000 grams (8 lb 13 oz) or 4500 grams (9 lb 15 oz), 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.^[7] 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

Pre-diabetes indicates 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. Many people destined to develop type 2 diabetes spend many years in a state of pre-diabetes which has been termed "America's largest healthcare epidemic."^[8]:10–11

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.^[9]

Following is a comprehensive list of other causes of diabetes:^[10]

Genetic defects of β-cell Function Maturity onset diabetes of the young (MODY) Mitochondrial DNA mutations Genetic defects in insulin processing or insulin action Defects in proinsulin conversion Insulin gene mutations Insulin receptor mutations Exocrine Pancreatic Defects Chronic pancreatitis Pancreatectomy Pancreatic neoplasia Cystic fibrosis Hemochromatosis Fibrocalculous pancreatopathy

Endocrinopathies Growth hormone excess (acromegaly) Cushing syndrome Hyperthyroidism Pheochromocytoma Glucagonoma Infections Cytomegalovirus infection Coxsackievirus B Drugs Glucocorticoids Thyroid hormone β-adrenergic agonists

Signs and symptoms

Overview of the most significant symptoms of diabetes.

The classical symptoms of diabetes are polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).^[11] Symptoms may develop rapidly (weeks or months) in type 1 diabetes while in type 2 diabetes they usually develop much more slowly and may be subtle or absent.

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.

People (usually with type 1 diabetes) may also present with diabetic ketoacidosis, a state of metabolic dysregulation characterized by the smell of acetone; a rapid, deep breathing known as Kussmaul breathing; nausea; vomiting and abdominal pain; and an altered states of consciousness.

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. Often, the patient has been drinking extreme amounts of sugar-containing drinks, leading to a vicious circle in regard to the water loss.

A number of skin rashes can occur in diabetes that are collectively known as diabetic dermadromes.

Causes

The cause of diabetes depends on the type. Type 2 diabetes is due primarily to lifestyle factors and genetics.^[12]

Type 1 diabetes is also partly inherited and then triggered by certain infections, with some evidence pointing at Coxsackie B4 virus. 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.

Pathophysiology

This section does not cite any references or sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be and removed. (November 2009)

The fluctuation of blood sugar (red) and the sugar-lowering hormone insulin (blue) in humans during the course of a day with three meals. One of the effects of a sugar-rich vs a starch-rich meal is highlighted. 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.

Humans are capable of digesting some carbohydrates, in particular those most common in food; starch, and some disaccharides such as sucrose, are converted within a few hours to simpler forms most notably the monosaccharide glucose, the principal carbohydrate energy source used by the body. 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. The rest are passed on for processing by gut flora largely in the colon. 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 the opposite manner to insulin. Glucose thus forcibly produced from internal liver cell stores (as glycogen) re-enters the bloodstream; muscle cells lack the necessary export mechanism. Normally liver cells do this when the level of insulin is low (which normally correlates with low levels of blood glucose).

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 have its usual effect so that 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.

When the glucose concentration in the blood is raised beyond its renal threshold (about 10 mmol/L, although this may be altered in certain conditions, such as pregnancy), 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.

Diagnosis

See also: Glycosylated hemoglobin and Glucose tolerance test

2006 WHO Diabetes criteria^[13]

Condition	2 hour glucose	Fasting glucose
	mmol/l(mg/dl)	mmol/l(mg/dl)
Normal	<7.8 (<140)	<6.1 (<110)
Diabetes mellitus	≥11.1 (≥200)	≥7.0 (≥126)

Diabetes mellitus is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of the following:^[9]

• Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL).
• Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) two hours after a 75 g oral glucose load as in a glucose tolerance test.
• Symptoms of hyperglycemia and casual plasma glucose ≥ 11.1 mmol/L (200 mg/dL).
• Glycated hemoglobin (Hb A1C) ≥ 6.5%.^[14]

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. It is preferable 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.^[15] According to the current definition, two fasting glucose measurements above 126 mg/dL (7.0 mmol/L) is considered diagnostic for diabetes mellitus.

People with fasting glucose levels from 100 to 125 mg/dL (5.6 to 6.9 mmol/L) are considered to have impaired fasting glucose. Patients with plasma glucose at or above 140 mg/dL (7.8 mmol/L), but not over 200 mg/dL (11.1 mmol/L), 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.^[16]

Management

Main article: Diabetes management

Diabetes mellitus is a chronic disease which is difficult to cure. Management concentrates on keeping blood sugar levels as close to normal ("euglycemia") as possible without presenting undue patient danger. This can usually be with close dietary management, exercise, and use of appropriate medications (insulin only in the case of type 1 diabetes mellitus. Oral medications may be used in the case of type 2 diabetes, as well as insulin).

Patient education, understanding, and participation is vital since the complications of diabetes are far less common and less severe in people who have well-managed blood sugar levels.^[17][18] Wider health problems may accelerate the deleterious effects of diabetes. These include smoking, elevated cholesterol levels, obesity, high blood pressure, and lack of regular exercise.

Lifestyle modifications

Main article: Diabetic diet

There are roles for patient education, dietetic support, sensible 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^[19] in patients with hypertension, cholesterol in those with dyslipidmia, as well as exercising more, smoking less or ideally not at all, consuming a recommended diet^{[citation needed]}. Patients with foot problems are also recommended to wear diabetic socks^{[citation needed]}, and possibly diabetic shoes^{[citation needed]}.

Medications

Oral medications

Main article: Anti-diabetic drug

Routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes.^[20]

Insulin

Main article: Insulin therapy

Type 1 treatments usually include combinations of regular or NPH insulin, and/or synthetic insulin analogs.

Support

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 for their own health care (e.g. in the US, and in much of the undeveloped world).

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.

Prognosis

Main article: Prognosis of diabetes mellitus

Diabetes doubles the risk of vascular problems, including cardiovascular disease.^[21]

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.^[22] 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.

Except in the case of type 1 diabetes, which always requires insulin replacement, the way type 2 diabetes is managed may change 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.^[23] Age-related glucose intolerance in humans is often accompanied by insulin resistance, but circulating insulin levels are similar to those of younger people.^[24] 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.^[25] Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.^[26]

Epidemiology

Prevalence of diabetes worldwide in 2000 (per 1000 inhabitants). World average was 2.8%. no data ≤ 7.5 7.5–15 15–22.5 22.5–30 30–37.5 37.5–45 45–52.5 52.5–60 60–67.5 67.5–75 75–82.5 ≥ 82.5 Disability-adjusted life year for diabetes mellitus per 100,000 inhabitants in 2002.^[27] no data ≤ 100 100-200 200-300 300-400 400-500 500-600 600-700 700-800 800-900 900-1000 1000-1500 ≥ 1500

In 2000, according to the World Health Organization, at least 171 million people worldwide suffer from diabetes, or 2.8% of the population.^[2] Its incidence is increasing rapidly, and it is estimated that by 2030, this number will almost double.^[2] 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.^[2] 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.^[2]

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.^[28]

The Centers for Disease Control has termed the change an epidemic.^[29] 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. 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.^[30][31]

According to the American Diabetes Association, approximately 18.3% (8.6 million) of Americans age 60 and older have diabetes.^[32] 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.^[23]

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.^[33] 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) (pronounced /ˌdaɪ.əˈbiːtiːz/ or /ˌdaɪ.əˈbiːtɨs/; /mɨˈlaɪtəs/ or /ˈmɛlɨtəs/) 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.^[34]

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."^[35]

Sushruta (6th century BCE) identified diabetes and classified it as Medhumeha.^[36] He further identified it with obesity and sedentary lifestyle, advising exercises to help "cure" it.^[36] 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 Chinese, Japanese and Korean 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.^[37]

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.^[38] 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.^[39] 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.

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.^[40] 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.^[41]

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.^[42]

Other landmark discoveries include:^[38]

• 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)^[43]
• 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,^[44] 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.

Society and culture

The 1990 "St Vincent Declaration"^[45][46] 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.^[47]

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.^[48]

References

1. ^ "Diabetes Blue Circle Symbol". International Diabetes Federation. 17 March 2006. http://www.diabetesbluecircle.org.
2. ^ ^{a b c d e} Wild S, Roglic G, Green A, Sicree R, King H (May 2004). "Global prevalence of diabetes: estimates for 2000 and projections for 2030". Diabetes Care 27 (5): 1047–53. doi:10.2337/diacare.27.5.1047. PMID 15111519.
3. ^ "Type 2 Diabetes Overview". Web MD. http://diabetes.webmd.com/guide/type-2-diabetes.
4. ^ "Other "types" of diabetes". American Diabetes Association. August 25, 2005. http://www.diabetes.org/other-types.jsp.
5. ^ "Diseases: Johns Hopkins Autoimmune Disease Research Center". http://autoimmune.pathology.jhmi.edu/diseases.cfm?systemID=3&DiseaseID=23. Retrieved 2007-09-23.
6. ^ Rother KI (April 2007). "Diabetes treatment—bridging the divide". The New England Journal of Medicine 356 (15): 1499–501. doi:10.1056/NEJMp078030. PMID 17429082.
7. ^ 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.
8. ^ Handelsman, Yehuda, MD. "A Doctor's Diagnosis: Prediabetes." Power of Prevention, Vol 1, Issue 2, 2009.
9. ^ ^{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.
10. ^ Unless otherwise specified, reference is: Table 20-5 in Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
11. ^ Cooke DW, Plotnick L (November 2008). "Type 1 diabetes mellitus in pediatrics". Pediatr Rev 29 (11): 374–84; quiz 385. doi:10.1542/pir.29-11-374. PMID 18977856.
12. ^ Risérus U, Willett WC, Hu FB (January 2009). "Dietary fats and prevention of type 2 diabetes". Progress in Lipid Research 48 (1): 44–51. doi:10.1016/j.plipres.2008.10.002. PMID 19032965.
13. ^ "www.who.int" (pdf). World Health Organization. http://www.who.int/diabetes/publications/Definition%20and%20diagnosis%20of%20diabetes_new.pdf.
14. ^ ""Diabetes Care" January 2010". American Diabetes Association. http://care.diabetesjournals.org/content/33/Supplement_1/S3.full. Retrieved 2010-01-29.
15. ^ Saydah SH, Miret M, Sung J, Varas C, Gause D, Brancati FL (August 2001). "Postchallenge hyperglycemia and mortality in a national sample of U.S. adults". Diabetes Care 24 (8): 1397–402. doi:10.2337/diacare.24.8.1397. PMID 11473076.
16. ^ 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 2008-07-20.
17. ^ Nathan DM, Cleary PA, Backlund JY, et al. (December 2005). "Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes". The New England Journal of Medicine 353 (25): 2643–53. doi:10.1056/NEJMoa052187. PMID 16371630.
18. ^ "The effect of intensive diabetes therapy on the development and progression of neuropathy. The Diabetes Control and Complications Trial Research Group". Annals of Internal Medicine 122 (8): 561–8. April 1995. doi:10.1059/0003-4819-122-8-199504150-00001 (inactive 2009-10-31). PMID 7887548. http://www.annals.org/cgi/pmidlookup?view=long&pmid=7887548.
19. ^ Adler AI, Stratton IM, Neil HA, et al. (August 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.
20. ^ Pignone M, Alberts MJ, Colwell JA, et al. (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. PMID 20508233.
21. ^ "Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies : The Lancet". http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2960484-9/fulltext.
22. ^ "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
23. ^ ^{a b} Harris MI, Flegal KM, Cowie CC, et al. (April 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.
24. ^ Chang AM, Halter JB (January 2003). "Aging and insulin secretion". American Journal of Physiology. Endocrinology and Metabolism 284 (1): E7–12. doi:10.1152/ajpendo.00366.2002 (inactive 2009-10-31). PMID 12485807.
25. ^ "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 2007-05-14.
26. ^ "NEJM -- Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults". http://content.nejm.org/cgi/content/short/362/9/800.
27. ^ "Mortality and Burden of Disease Estimates for WHO Member States in 2002" (xls). World Health Organization. 2002. http://www.who.int/entity/healthinfo/statistics/bodgbddeathdalyestimates.xls.
28. ^ http://www.cdc.gov/Features/diabetesfactsheet/
29. ^ "CDC's Diabetes Program-News and Information-Press Releases-October 26, 2000". http://www.cdc.gov/Diabetes/news/docs/010126.htm. Retrieved 2008-06-23.
30. ^ Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF (October 2003). "Lifetime risk for diabetes mellitus in the United States". JAMA 290 (14): 1884–90. doi:10.1001/jama.290.14.1884. PMID 14532317.
31. ^ American Diabetes Association (2005). "Total Prevalence of Diabetes & Pre-diabetes". http://www.diabetes.org/diabetes-statistics/prevalence.jsp. Retrieved 2006-03-17.
32. ^ "Seniors and Diabetes". Elderly And Diabetes-Diabetes and Seniors. LifeMed Media. 2006. http://www.dlife.com/dLife/do/ShowContent/daily_living/seniors/. Retrieved 2007-05-14.
33. ^ Australian Institute for Health and Welfare. "Diabetes, an overview". http://www.aihw.gov.au/indigenous/health/diabetes.cfm. Retrieved 2008-06-23.
34. ^ Dobson, M. (1776). "Nature of the urine in diabetes". Medical Observations and Inquiries 5: 298–310.
35. ^ Medvei, Victor Cornelius (1993). The history of clinical endocrinology. Carnforth, Lancs., U.K: Parthenon Pub. Group. pp. 23–34. ISBN 1-85070-427-9.
36. ^ ^{a b} Dwivedi, Girish & Dwivedi, Shridhar (2007). History of Medicine: Sushruta – the Clinician – Teacher par Excellence. National Informatics Centre (Government of India).
37. ^ Nabipour, I. (2003). "Clinical Endocrinology in the Islamic Civilization in Iran". International Journal of Endocrinology and Metabolism 1: 43–45 [44–5].
38. ^ ^{a b} Patlak M (December 2002). "New weapons to combat an ancient disease: treating diabetes". The FASEB Journal 16 (14): 1853. PMID 12468446.
39. ^ Von Mehring J, Minkowski O. (1890). "Diabetes mellitus nach pankreasexstirpation". Arch Exp Pathol Pharmakol 26: 371–387. doi:10.1007/BF01831214.
40. ^ Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA (November 1991). "Pancreatic extracts in the treatment of diabetes mellitus: preliminary report. 1922". CMAJ 145 (10): 1281–6. PMID 1933711.
41. ^ 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.
42. ^ Department of Health (Malta), 1897–1972:Annual Reports.
43. ^ Yalow RS, Berson SA (July 1960). "Immunoassay of endogenous plasma insulin in man". The Journal of Clinical Investigation 39: 1157–75. doi:10.1172/JCI104130. PMID 13846364.
44. ^ The Diabetes Control And Complications Trial Research Group (September 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". The New England Journal of Medicine 329 (14): 977–86. doi:10.1056/NEJM199309303291401. PMID 8366922.
45. ^ Theodore H. Tulchinsky, Elena A. Varavikova (2008). The New Public Health, Second Edition. New York: Academic Press. p. 200. ISBN 0-12-370890-7.
46. ^ Piwernetz K, Home PD, Snorgaard O, Antsiferov M, Staehr-Johansen K, Krans M (May 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". Diabetic Medicine 10 (4): 371–7. doi:10.1111/j.1464-5491.1993.tb00083.x. PMID 8508624.
47. ^ 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.
48. ^ Stewart WF, Ricci JA, Chee E, Hirsch AG, Brandenburg NA (June 2007). "Lost productive time and costs due to diabetes and diabetic neuropathic pain in the US workforce". J. Occup. Environ. Med. 49 (6): 672–9. doi:10.1097/JOM.0b013e318065b83a. PMID 17563611.

External links

Find more about Diabetes mellitus on Wikipedia's sister projects:
	Definitions from Wiktionary
	Textbooks from Wikibooks
	Quotations from Wikiquote
	Source texts from Wikisource
	Images and media from Commons
	News stories from Wikinews
	Learning resources from Wikiversity

• Diabetes at the Open Directory Project
• American Diabetes Association
• IDF Diabetes Atlas
• International Diabetes Federation
• National Diabetes Education Program
• Peers for Progress
• World Diabetes Day

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 6) · complications (coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy, cardiomyopathy) insulin receptor (Rabson–Mendenhall syndrome) · Insulin resistance Hyperfunction Hypoglycemia · beta cell (Hyperinsulinism) · G cell (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: enzymatic (5-alpha-reductase deficiency, 17-beta-hydroxysteroid dehydrogenase deficiency) · Androgen receptor (Androgen insensitivity syndrome) general: Hypogonadism (Delayed puberty) · Hypergonadism (Precocious puberty) Height Gigantism · Dwarfism/Short stature (Laron syndrome, Psychosocial) Multiple Autoimmune polyendocrine syndrome (APS1, APS2) · Carcinoid syndrome · Multiple endocrine neoplasia (1, 2A, 2B) · Progeria (Werner syndrome, Acrogeria, Metageria) · Woodhouse-Sakati syndrome : END //// ()//, / , drug (///)

Diabetes (E10-E14, 250) Types of diabetes Prediabetes (Impaired fasting glucose, Impaired glucose tolerance) Type 1 · Type 2 · MODY · NDM (Transient, Permanent) Diabetes and pregnancy: Gestational diabetes Blood tests Blood sugar · Glycosylated hemoglobin · Glucose tolerance test · Fructosamine Diabetes management Diabetic diet · Anti-diabetic drugs · Insulin therapy · Glossary of diabetes Complications/prognosis Diabetic comas (Diabetic hypoglycemia, Diabetic ketoacidosis, Nonketotic hyperosmolar) · Diabetic angiopathy · Diabetic myonecrosis · Diabetic nephropathy · Diabetic neuropathy · Diabetic retinopathy · Diabetic cardiomyopathy · Diabetic dermadrome (Diabetic dermopathy, Diabetic bulla, Diabetic cheiroarthropathy, Neuropathic ulcer) : END //// ()//, / , drug (///)

Categories: Diabetes | Medical conditions related to obesity | Nutrition

 

 

See Also:

 

What Links Here:

• Home

 

Recently Viewed Pages:

• Shopping: Food: Produce: Vegetables: Sea Vegetables: Directory
• Ergonomics: Encyclopedia
• Home
• DASH Diet
• Healthy Diet: Images
• Copper
• Nutrition
• Images
• Shopping: Food: Health Food: Grains: Directory
• Shopping: Health: Nutrition: Green Foods: Directory

 

Most Popular Pages:

• Home
• Healthy Diet Pyramid: Images
• Tony Gonzalez the All-Pro Diet: News
• Ice Cream: Encyclopedia
• Fitness
• Bean: Answers
• BMI
• Forensic Pathologist: Answers
• Seed: Encyclopedia
• Search Terms

Related 'Diabetes' Searches:

related terms:	Gestational Diabetes	Diabetes Mellitus	Insulin	Blood Sugar
	Insulin Secretion	Blood Glucose	Type	Polyuria
	Blood Glucose Levels	Insulin Levels	Body Cells	Diabetes Mellitus Type

---

top user searches:	"diabetes mellitus pics images"	►

---

or search for "Diabetes" in:		Web:		The Entire Web	Related Sites	Web Directories
		This Site:		Page Titles	Karr Network Sites*
		News:		Headlines	Weather	Events	Blogs
		Reference:		Encyclopedia	Dictionary	eTexts	Quotes
				Local Map	Answers
		Multimedia:		Images	Videos
		People:		Discussion Groups	Social Networking
		Shopping:		General Merch.	Consumer Opinion	Auctions	Classifieds

 

---

The Entire Web Web Directories Related* Sites Karr Network Sites* Page Titles Headlines Weather Events Blogs Encyclopedia Dictionary eTexts Quotes Answers Local Map Videos Images Social Networking Discussion Groups General Items Auctions Classifieds Consumer Opinion

Sitemap News Dictionary Encyclopedia Blogs Answers Videos Images Shopping Directory More…