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March 26, 2016
Table of Contents

1 Introduction
diabetes mellitus

Wikipedia

 

Diabetes mellitus , often simply referred to as diabetes ???is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).

There are three main types of diabetes:

  • Type 1 diabetes : results from the body's failure to produce insulin, and presently requires the person to inject insulin. (Also referred to as insulin-dependent diabetes mellitus, IDDM for short, and juvenile diabetes.)

  • Type 2 diabetes : results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency.

  • Gestational diabetes: 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 .

All forms of diabetes have been treatable since insulin 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 have been tried with limited success in type 1 DM; gastric bypass surgery has been successful in many with morbid obesity and type 2 DM. Gestational diabetes usually resolves after delivery. Diabetes without proper treatments can cause many complications. Acute complications include hypoglycemia, diabetic ketoacidosis, or nonketotic hyperosmolar coma. Serious long-term complications include cardiovascular disease, chronic renal failure, retinal damage . Adequate treatment of diabetes is thus important, as well as blood pressure control and lifestyle factors such as smoking cessation and maintaining a healthy body weight .

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




The term diabetes , without qualification, usually refers to diabetes mellitus, which roughly translates to excessive sweet urine (known as " glycosuria"). Several rare conditions are also named diabetes. The most common of these is diabetes insipidus in which large amounts of urine are produced ( polyuria), 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, 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)




Most cases of diabetes mellitus fall into three broad categories: type 1 , type 2 , and gestational diabetes. A few other types are described.

Type 1 diabetes

Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans 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 mediated autoimmune attack. 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

Type 2 diabetes mellitus is characterized by insulin resistance which may be combined with relatively reduced insulin secretion. The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. 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 that improve insulin sensitivity or reduce glucose production by the liver.

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. Labor 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 the number of American women entering pregnancy with preexisting diabetes is increasing. In fact the rate of diabetes in expectant mothers has more than doubled in the past 6 years. 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."

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.

Following is a comprehensive list of other causes of diabetes:

  • Genetic defects of ??-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

  • * ??-adrenergic agonists




The classical symptoms of diabetes are polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger). 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.




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

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.




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 rest are passed on for processing by gut flora largely in the colon. Insulin is released into the blood by beta cells (??-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.




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

  • 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%.

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. 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.




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.

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

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.

Medications

Oral medications

Routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes.

Insulin

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.




Diabetes doubles the risk of vascular problems, including cardiovascular disease.

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. 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. Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.




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

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.

The Centers for Disease Control has termed the change an epidemic. 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.

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

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. Preventative community health programs such as Sugar Man (diabetes education) are showing some success in tackling this problem.




The term diabetes (, diab??t??s ) ( or ; or ) was coined by Aretaeus of Cappadocia. It was derived from the Greek verb ????????????????????, diaba??nein , 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 diab??t??s meant "one that straddles," or specifically "a compass, siphon." The sense "siphon" gave rise to the use of diab??t??s 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.

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."

Sushruta (6th century BCE) identified diabetes and classified it as Medhumeha . 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 (?????????) 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.

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.

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.

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.

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.

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.

Other landmark discoveries include:

  • 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)

  • The three-dimensional structure of insulin ()

  • 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, 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. The purified insulin is distributed to pharmacies for use by diabetes patients.




The 1990 " St. Vincent Declaration" 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.

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.




  • Risk factors in pregnancy

  • Taking Control of your Diabetes (educational organization)





  • 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



This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "diabetes mellitus".


Last Modified:   2010-11-25


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