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Diabetes mellitus | Understanding and definition of Diabetes mellitus

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).

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.

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 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 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.

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.":10–11

Latent autoimmune diabetes of adults is a condition in which Type 1 diabetes develops in adults. Adults with LADA are frequently initially misdiagnosed as having Type 2 diabetes, based on age rather than etiology.

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.

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.

Following is a comprehensive list of other causes of diabetes:

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
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 (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.

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.

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.

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

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