Diabetes/ja: Difference between revisions

{{About|the common insulin disorder|the urine hyper-production disorder|Diabetes insipidus}}

| name          = Diabetes mellitus

| alt          = A hollow circle with a thick blue border and a clear centre

| caption      = Universal blue circle symbol for diabetes

| field        = [[Endocrinology]]

* [[polyuria|Frequent urination]]

* [[polydipsia|Increased thirst]]

* [[polyphagia|Increased hunger]]

* Metabolic imbalances

* Cardiovascular diseases

* Nerve and brain damage

* Kidney failure

* Gastrointestinal changes

| duration      = Remission may occur, but diabetes is often life-long

* Type 1 diabetes

* Type 2 diabetes

* Gestational diabetes

| causes        = Insulin insufficiency or gradual resistance

* '''Type 1''': [[Family history]]

* '''Type 2''': [[Obesity]], lack of exercise, [[Heredity|genetics]], air pollution

* High [[blood sugar]]

* Increased [[HbA1c]]

* [[Lifestyle causes of type 2 diabetes|Lifestyle changes]]

* [[Diabetes medication]]

* [[Insulin (medication)|Insulin]]

* [[Anti-diabetic medication|Anti-hyperglycaemics]]

'''Diabetes mellitus''', often known simply as '''diabetes''', is a group of common [[endocrine disease]]s characterized by sustained [[hyperglycemia|high blood sugar levels]]. Diabetes is due to either the [[pancreas]] not producing enough [[insulin]], or the cells of the body becoming unresponsive to the hormone's effects. Classic symptoms include thirst, [[polyuria]], weight loss, and [[blurred vision]]. If left untreated, the disease can lead to various health complications, including disorders of the [[Cardiovascular disease|cardiovascular system]], [[Diabetic retinopathy|eye]], [[Diabetic nephropathy|kidney]], and [[Diabetic neuropathy|nerves]]. Untreated or poorly treated diabetes accounts for approximately 1.5 million deaths every year.

The major types of diabetes are [[Type 1 diabetes|type 1]] and [[Type 2 diabetes|type 2]], though other forms also exist. The most common treatment for type 1  is [[insulin replacement therapy]] (insulin injections), while [[Diabetes medication|anti-diabetic medications]] (such as [[metformin]] and [[semaglutide]]) and [[Lifestyle medicine|lifestyle modifications]] can be used to manage type 2. [[Gestational diabetes]], a form that arises during [[pregnancy]] in some women, normally resolves shortly after delivery.

As of 2021, an estimated 537 million people had diabetes worldwide accounting for 10.5% of the adult population, with type 2 making up about 90% of all cases. It is estimated that by 2045, approximately 783 million adults, or 1 in 8, will be living with diabetes, representing a 46% increase from the current figures. The prevalence of the disease continues to increase, most dramatically in low- and middle-income nations. Rates are similar in women and men, with diabetes being the seventh leading cause of death globally. The global expenditure on diabetes-related healthcare is an estimated US$760 billion a year.

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==Signs and symptoms==

[[File:Main symptoms of diabetes.svg|thumb|upright=1.5|Overview of the most significant symptoms of diabetes]] [[File:Diabetes complications.jpg|thumb|Retinopathy, nephropathy, and neuropathy are potential complications of diabetes]]The classic symptoms of untreated diabetes are [[polyuria]], thirst, and weight loss. Several other non-specific signs and symptoms may also occur, including fatigue, blurred vision, and genital itchiness due to [[Candidiasis|''Candida'' infection]]. About half of affected individuals may also be asymptomatic. Type 1 presents abruptly following a pre-clinical phase, while type 2 has a more insidious onset; patients may remain asymptomatic for many years.

[[Diabetic ketoacidosis]] is a medical emergency that occurs most commonly in type 1, but may also occur in type 2 if it has been longstanding or if the individual has significant β-cell dysfunction. Excessive production of [[ketone bodies]] leads to signs and symptoms including nausea, vomiting, abdominal pain, the smell of [[acetone]] in the breath, deep breathing known as [[Kussmaul breathing]], and in severe cases [[Altered level of consciousness|decreased level of consciousness]]. [[Hyperosmolar hyperglycemic state]] is another emergency characterised by dehydration secondary to severe hyperglycaemia, with resultant [[hypernatremia]] leading to an altered mental state and possibly [[coma]].

[[Hypoglycemia|Hypoglycaemia]] is a recognised complication of insulin treatment used in diabetes. An acute presentation can include mild symptoms such as [[Perspiration|sweating]], trembling, and [[palpitations]], to more serious effects including [[Delirium|impaired cognition]], confusion, [[seizure]]s, [[coma]], and rarely death. Recurrent hypoglycaemic episodes may lower the glycaemic threshold at which symptoms occur, meaning mild symptoms may not appear before cognitive deterioration begins to occur.

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===Long-term complications===

{{Main|Complications of diabetes}}

The major long-term complications of diabetes relate to damage to [[blood vessel]]s at both [[Macrovascular disease|macrovascular]] and [[Microvascular disease|microvascular]] levels. Diabetes doubles the risk of [[cardiovascular disease]], and about 75% of deaths in people with diabetes are due to [[coronary artery disease]]. Other macrovascular morbidities include [[stroke]] and [[peripheral artery disease]].

Microvascular disease affects the [[eye]]s, [[kidney]]s, and [[nerve]]s. Damage to the retina, known as [[diabetic retinopathy]], is the most common cause of blindness in people of working age. The eyes can also be affected in other ways, including development of [[cataract]] and [[glaucoma]]. It is recommended that people with diabetes visit an [[optometrist]] or [[ophthalmologist]] once a year.

[[Diabetic nephropathy]] is a major cause of [[chronic kidney disease]], accounting for over 50% of patients on [[Kidney dialysis|dialysis]] in the United States. [[Diabetic neuropathy]], damage to nerves, manifests in various ways, including [[sensory loss]], [[neuropathic pain]], and [[autonomic dysfunction]] (such as [[Orthostatic hypotension|postural hypotension]], [[Diarrhea|diarrhoea]], and [[erectile dysfunction]]). Loss of pain sensation predisposes to trauma that can lead to [[Diabetic foot|diabetic foot problems]] (such as [[ulcer]]ation), the most common cause of non-traumatic lower-limb [[amputation]].

There is a link between [[cognitive deficit]] and diabetes; studies have shown that diabetic individuals are at a greater risk of cognitive decline, and have a greater rate of decline compared to those without the disease. The condition also predisposes to [[Falls in older adults|falls in the elderly]], especially those treated with [[insulin]].

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==Causes==

|+Comparison of type 1 and 2 diabetes

! Feature !! Type 1 diabetes !! Type 2 diabetes

! Onset

| Sudden||Gradual

! Age at onset

| Mostly in children || Mostly in adults

! Body size

| Thin or normal || Often [[obese]]

! [[diabetic ketoacidosis|Ketoacidosis]]

| Common || Rare

! [[Autoantibodies]]

| Usually present || Absent

! Endogenous insulin

| Low or absent || Normal, decreased<br /> or increased

! Heritability

! Prevalence

(age standardized)

| <2 per 1,000|| ~6% (men), ~5% (women)

Diabetes is classified by the [[World Health Organization]] into six categories: [[type 1 diabetes]], [[type 2 diabetes]], hybrid forms of diabetes (including include [[Latent autoimmune diabetes of adults|slowly evolving, immune-mediated diabetes of adults]] and [[Ketosis-prone diabetes|ketosis-prone type 2 diabetes]]), hyperglycemia first detected during pregnancy, "other specific types", and "unclassified diabetes". Diabetes is a more variable disease than once thought, and individuals may have a combination of forms.

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===Type 1===

{{Main|Type 1 diabetes}}

Type 1 accounts for 5 to 10% of diabetes cases and is the most common type diagnosed in patients under 20 years; however, the older term "juvenile-onset diabetes" is no longer used as the disease not uncommonly has onset in adulthood. The disease is characterized by loss of the insulin-producing [[beta cell]]s of the [[pancreatic islets]], leading to severe insulin deficiency, and can be further classified as [[immune-mediated]] or [[Idiopathic disease|idiopathic]] (without known cause). The majority of cases are immune-mediated, in which a [[T cell]]-mediated [[autoimmunity|autoimmune]] attack causes loss of beta cells and thus insulin deficiency. Patients often have irregular and unpredictable blood sugar levels due to very low insulin and an impaired counter-response to hypoglycaemia.

[[File:Type 1 Diabetes Mellitus.jpg|thumb|Autoimmune attack in type 1 diabetes.]]

Type&nbsp;1 diabetes is partly [[Genetic disorder|inherited]], with multiple genes, including certain [[Human leukocyte antigen|HLA genotypes]], known to influence the risk of diabetes. In genetically susceptible people, the onset of diabetes can be triggered by one or more [[environmental factor]]s, such as a [[viral infection]] or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans.

Type 1 diabetes can occur at any age, and a significant proportion is diagnosed during adulthood. [[Latent autoimmune diabetes of adults]] (LADA) is the diagnostic term applied when type 1 diabetes develops in adults; it has a slower onset than the same condition in children. Given this difference, some use the unofficial term "type 1.5 diabetes" for this condition. Adults with LADA are frequently initially misdiagnosed as having type 2 diabetes, based on age rather than a cause. LADA leaves adults with higher levels of insulin production than type 1 diabetes, but not enough insulin production for healthy blood sugar levels.

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===Type 2===

{{Main|Type 2 diabetes}}

[[File:Type 2 Diabetes Mellitus.jpg|thumb|Reduced insulin secretion or weaker effect of insulin on its receptor leads to high glucose content in the blood.]]

Type 2 diabetes 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 cases due to a known defect are classified separately. Type 2 diabetes is the most common type of diabetes mellitus accounting for 95% of diabetes. Many people with type 2 diabetes have evidence of [[prediabetes]] (impaired fasting glucose and/or impaired glucose tolerance) before meeting the criteria for type 2 diabetes. The progression of prediabetes to overt type 2 diabetes can be slowed or reversed by lifestyle changes or [[Anti-diabetic drug|medications]] that improve insulin sensitivity or reduce the [[Glycogenolysis|liver's glucose production]].

Type 2 diabetes is primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important to the development of type 2 diabetes, including [[obesity]] (defined by a [[body mass index]] of greater than 30), lack of [[physical activity]], poor [[Diet (nutrition)|diet]], [[stress (biology)|stress]], and [[urbanization]]. Excess body fat is associated with 30% of cases in people of Chinese and Japanese descent, 60–80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders. Even those who are not obese may have a high [[waist–hip ratio]].

Dietary factors such as [[sugar]]-sweetened drinks are associated with an increased risk. The type of [[fat]]s in the diet is also important, with [[saturated fat]] and [[trans fat]]s increasing the risk and [[polyunsaturated fat|polyunsaturated]] and [[monounsaturated fat]] decreasing the risk. Eating [[white rice]] excessively may increase the risk of diabetes, especially in Chinese and Japanese people. Lack of physical activity may increase the risk of diabetes in some people.

[[Adverse Childhood Experiences Study|Adverse childhood experiences]], including abuse, neglect, and household difficulties, increase the likelihood of type 2 diabetes later in life by 32%, with [[neglect]] having the strongest effect.

[[Antipsychotic|Antipsychotic medication]] side effects (specifically metabolic abnormalities, [[dyslipidemia]] and weight gain) and unhealthy lifestyles (including poor diet and decreased [[physical activity]]), are potential risk factors.

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===Gestational diabetes===

{{Main|Gestational diabetes}}

Gestational diabetes resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2–10% of all [[pregnancy|pregnancies]] and may improve or disappear after delivery. It is recommended that all pregnant women get tested starting around 24–28 weeks gestation. It is most often diagnosed in the second or third trimester because of the increase in insulin-antagonist hormone levels that occurs at this time. However, after pregnancy approximately 5–10% of women with gestational diabetes are found to have another form of diabetes, most commonly type 2. Gestational diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy. Management may include dietary changes, blood glucose monitoring, and in some cases, insulin may be required.

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 heart defect|congenital heart]] and [[central nervous system]] abnormalities, and [[skeletal muscle]] malformations. Increased levels of insulin in a fetus's blood may inhibit fetal [[surfactant]] production and cause [[infant respiratory distress syndrome]]. A [[Bilirubin#Hyperbilirubinemia|high blood bilirubin level]] may result from [[hemolysis|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 [[caesarean section]] may be performed if there is marked [[fetal distress]] or an increased risk of injury associated with macrosomia, such as [[shoulder dystocia]].

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===Other types===

[[Maturity onset diabetes of the young]] (MODY) is a rare [[Dominance (genetics)|autosomal dominant]] inherited form of diabetes, due to one of several single-gene mutations causing defects in insulin production. It is significantly less common than the three main types, constituting 1–2% of all cases. The name of this disease refers to early hypotheses as to its nature. Being due to a defective gene, this disease varies in age at presentation and in severity according to the specific gene defect; thus, there are at least 13 subtypes of MODY. People with MODY often can control it without using insulin.

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&nbsp;2 diabetes); this form is very uncommon. Genetic mutations ([[Dominance (genetics)|autosomal]] or [[Mitochondrion|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 receptor|insulin-antagonistic]] [[hormone]]s 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, whereas others increase [[insulin resistance]] (especially [[glucocorticoid]]s which can provoke "[[steroid diabetes]]"). The [[ICD-10]] (1992) diagnostic entity, ''malnutrition-related diabetes mellitus'' (ICD-10 code E12), was deprecated by the [[World Health Organization]] (WHO) when the current taxonomy was introduced in 1999.

Yet another form of diabetes that people may develop is [[double diabetes]]. This is when a type 1 diabetic becomes insulin resistant, the hallmark for type 2 diabetes or has a family history for type 2 diabetes. It was first discovered in 1990 or 1991.

* Genetic defects of β-cell function

** [[Maturity onset diabetes of the young]]

** Mitochondrial DNA mutations

* Genetic defects in insulin processing or insulin action

** Defects in [[proinsulin]] conversion

** Insulin gene mutations

** Insulin receptor mutations

* Exocrine pancreatic defects (see [[Type 3c diabetes]], i.e. pancreatogenic diabetes)

** [[Chronic pancreatitis]]

** [[Pancreatectomy]]

** [[Pancreatic neoplasia]]

** [[Cystic fibrosis]]

** [[Hemochromatosis]]

** [[Fibrocalculous pancreatopathy]]

* [[Endocrinopathies]]

** Growth hormone excess ([[acromegaly]])

** [[Cushing syndrome]]

** [[Hyperthyroidism]]

** [[Hypothyroidism]]

** [[Pheochromocytoma]]

** [[Glucagonoma]]

* Infections

** [[Cytomegalovirus infection]]

** [[Coxsackie B4 virus|Coxsackievirus B]]

* Drugs

** [[Glucocorticoids]]

** [[Thyroid hormone]]

** [[β-adrenergic agonist]]s

** [[Statins]]

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==Pathophysiology==

[[File:Suckale08 fig3 glucose insulin day.png|thumb|upright=1.4|The fluctuation of [[Blood sugar level|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 [[sucrose|sugar]]-rich vs a [[starch]]-rich meal is highlighted.]]

[[File:Glucose-insulin-release.svg|thumb|upright=1.4|Mechanism of insulin release in normal pancreatic [[beta cell]]s. Insulin production is more or less constant within the beta cells. Its release is triggered by food, chiefly food containing absorbable glucose.]]

[[Insulin]] is the principal hormone that regulates the uptake of [[glucose]] from the blood into most cells of the body, especially liver, adipose tissue and muscle, except smooth muscle, in which insulin acts via the [[IGF-1]]. Therefore, deficiency of insulin or the insensitivity of its [[Receptor (biochemistry)|receptors]] play a central role in all forms of diabetes mellitus.

The body obtains glucose from three main sources: the intestinal absorption of food; the breakdown of [[glycogen]] ([[glycogenolysis]]), the storage form of glucose found in the liver; and [[gluconeogenesis]], the generation of glucose from non-carbohydrate substrates in the body. Insulin plays a critical role in regulating glucose levels in the body. Insulin can inhibit the breakdown of glycogen or the process of gluconeogenesis, it can stimulate the transport of glucose into fat and muscle cells, and it can stimulate the storage of glucose in the form of glycogen.

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. Lower glucose levels result in decreased insulin release from the beta cells and in the breakdown of glycogen to glucose. This process is mainly controlled by the hormone [[glucagon]], which acts in the opposite manner to insulin.

If the amount of insulin available is insufficient, or if cells respond poorly to the effects of insulin ([[insulin resistance]]), or if the insulin itself is defective, then glucose is not absorbed properly by the body cells that require it, and is not stored appropriately in the liver and muscles. The net effect is persistently high levels of blood glucose, poor [[Protein biosynthesis|protein synthesis]], and other metabolic derangements, such as metabolic [[acidosis]] in cases of complete insulin deficiency.

When there is too much glucose in the blood for a long time, the [[kidneys]] cannot absorb it all (reach a threshold of [[reabsorption]]) and the extra glucose gets passed out of the body through [[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 is replaced osmotically from water in body cells and other body compartments, causing [[dehydration]] and increased thirst ([[polydipsia]]). In addition, intracellular glucose deficiency stimulates appetite leading to excessive food intake (polyphagia).

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==Diagnosis==

{{See also|Glycated hemoglobin|Glucose tolerance test}}

* [[Fasting glucose|Fasting plasma glucose level]] ≥&nbsp;7.0&nbsp;mmol/L (126&nbsp;mg/dL). For this test, blood is taken after a period of fasting, i.e. in the morning before breakfast, after the patient had sufficient time to fast overnight or at least 8 hours before the test.

* [[Plasma glucose]] ≥&nbsp;11.1&nbsp;mmol/L (200&nbsp;mg/dL) two hours after a 75&nbsp;gram oral glucose load as in a [[glucose tolerance test]] (OGTT)

* Symptoms of high blood sugar and plasma glucose ≥&nbsp;11.1&nbsp;mmol/L (200&nbsp;mg/dL) either while fasting or not fasting

* [[Glycated hemoglobin]] (HbA_1C) ≥&nbsp;48&nbsp;mmol/mol (≥&nbsp;6.5 [[Diabetes control and complications trial|DCCT]] %).

A positive result, in the absence of unequivocal high blood sugar, should be confirmed by a repeat of any of the above 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 at or above 7.0&nbsp;mmol/L (126&nbsp;mg/dL) is considered diagnostic for diabetes mellitus.

Per the WHO, people with fasting glucose levels from 6.1 to 6.9&nbsp;mmol/L (110 to 125&nbsp;mg/dL) are considered to have [[impaired fasting glycemia|impaired fasting glucose]]. People with plasma glucose at or above 7.8&nbsp;mmol/L (140&nbsp;mg/dL), but not over 11.1&nbsp;mmol/L (200&nbsp;mg/dL), two hours after a 75&nbsp;gram oral glucose load are considered to have [[impaired glucose tolerance]]. Of these two prediabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus, as well as cardiovascular disease. The [[American Diabetes Association]] (ADA) since 2003 uses a slightly different range for impaired fasting glucose of 5.6 to 6.9&nbsp;mmol/L (100 to 125&nbsp;mg/dL).

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

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==Prevention==

{{See also|Prevention of type 2 diabetes}}

There is no known [[Preventive healthcare|preventive]] measure for type&nbsp;1 diabetes. However, islet autoimmunity and multiple antibodies can be a strong predictor of the onset of type 1 diabetes.  Type&nbsp;2 diabetes—which accounts for 85–90% of all cases worldwide—can often be prevented or delayed by maintaining a [[normal body weight]], engaging in physical activity, and eating a healthy diet. Higher levels of physical activity (more than 90 minutes per day) reduce the risk of diabetes by 28%. Dietary changes known to be effective in helping to prevent diabetes include maintaining a diet rich in [[whole grain]]s and [[Dietary fiber|fiber]], and choosing good fats, such as the [[polyunsaturated fat]]s found in nuts, vegetable oils, and fish. Limiting sugary beverages and eating less red meat and other sources of [[saturated fat]] can also help prevent diabetes. Tobacco smoking is also associated with an increased risk of diabetes and its complications, so [[smoking cessation]] can be an important preventive measure as well.

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The relationship between type 2 diabetes and the main modifiable risk factors (excess weight, unhealthy diet, physical inactivity and tobacco use) is similar in all regions of the world. There is growing evidence that the underlying determinants of diabetes are a reflection of the major forces driving social, economic and cultural change: [[globalization]], urbanization, population aging, and the general [[health policy]] environment.

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==Management==

{{Main|Diabetes management}}

Learning about the disease and actively participating in the treatment is important, since complications are far less common and less severe in people who have well-managed blood sugar levels. The goal of treatment is an A1C level below 7%. Attention is also paid to other health problems that may accelerate the negative effects of diabetes. These include [[tobacco smoking|smoking]], [[hypertension|high blood pressure]], [[metabolic syndrome]] [[obesity]], and lack of regular [[exercise]]. [[Diabetic shoe|Specialized footwear]] is widely used to reduce the risk of [[diabetic foot ulcer]]s by relieving the pressure on the foot. Foot examination for patients living with diabetes should be done annually which includes sensation testing, foot [[biomechanics]], vascular integrity and foot structure.

Concerning those with severe [[Mental disorder|mental illness]], the efficacy of [[type 2 diabetes]] self-management interventions is still poorly explored, with insufficient scientific evidence to show whether these interventions have similar results to those observed in the general population.

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===Lifestyle===

{{See also|Diet in diabetes}}

People with diabetes can benefit from education about the disease and treatment, dietary changes, and exercise, with the goal of keeping both short-term and long-term blood glucose levels [[Diabetes management#Glycemic control|within acceptable bounds]]. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.

[[Weight loss]] can prevent progression from prediabetes to [[Diabetes mellitus|diabetes type 2]], decrease the risk of cardiovascular disease, or result in a partial remission in people with diabetes. No single dietary pattern is best for all people with diabetes. Healthy dietary patterns, such as the [[Mediterranean diet]], [[low-carbohydrate diet]], or [[DASH diet]], are often recommended, although evidence does not support one over the others. According to the ADA, "reducing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia", and for individuals with type 2 diabetes who cannot meet the glycemic targets or where reducing anti-glycemic medications is a priority, [[low-carbohydrate diet|low or very-low carbohydrate diet]]s are a viable approach. For overweight people with type 2 diabetes, any diet that achieves weight loss is effective.

A 2020 Cochrane systematic review compared several non-nutritive sweeteners to sugar, placebo and a nutritive low-calorie sweetener ([[tagatose]]), but the results were unclear for effects on HbA1c, body weight and adverse events. The studies included were mainly of very low-certainty and did not report on health-related quality of life, diabetes complications, all-cause mortality or socioeconomic effects.

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===Medications===

{{Main|Diabetes medication}}

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====Glucose control====

{{see also|Anti-diabetic medication}}

Most medications used to treat diabetes act by lowering [[glucose|blood sugar levels]] through different mechanisms. There is broad consensus that when people with diabetes maintain tight glucose control – keeping the glucose levels in their blood within normal ranges – they experience fewer complications, such as [[diabetic nephropathy|kidney problems]] or [[diabetic retinopathy|eye problems]]. There is however debate as to whether this is appropriate and [[cost effective]] for people later in life in whom the risk of hypoglycemia may be more significant.

There are a number of different classes of anti-diabetic medications. Type&nbsp;1 diabetes requires treatment with [[insulin]], ideally using a "basal bolus" regimen that most closely matches normal insulin release: long-acting insulin for the [[basal rate]] and short-acting insulin with meals. Type 2 diabetes is generally treated with medication that is taken by mouth (e.g. [[metformin]]) although some eventually require injectable treatment with insulin or [[GLP-1 agonist]]s.

[[Metformin]] is generally recommended as a first-line treatment for type&nbsp;2 diabetes, as there is good evidence that it decreases mortality. It works by decreasing the liver's production of glucose, and increasing the amount of glucose stored in peripheral tissue. Several other groups of drugs, mainly oral medication, may also decrease blood sugar in type 2 diabetes. These include agents that increase insulin release ([[sulfonylurea]]s), agents that decrease absorption of sugar from the intestines ([[acarbose]]), agents that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4) that inactivates incretins such as GLP-1 and GIP ([[sitagliptin]]), agents that make the body more sensitive to insulin ([[thiazolidinedione]]) and agents that increase the excretion of glucose in the urine ([[SGLT2 inhibitor]]s). When insulin is used in type 2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications.

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====Blood pressure lowering====

[[Cardiovascular disease]] is a serious complication associated with diabetes, and many international guidelines recommend blood pressure treatment targets that are lower than 140/90&nbsp;mmHg for people with diabetes. However, there is only limited evidence regarding what the lower targets should be. A 2016 systematic review found potential harm to treating to targets lower than 140 mmHg, and a subsequent systematic review in 2019 found no evidence of additional benefit from blood pressure lowering to between 130 – 140mmHg, although there was an increased risk of adverse events.

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2015 American Diabetes Association recommendations are that people with diabetes and albuminuria should receive an inhibitor of the renin-angiotensin system to reduce the risks of progression to end-stage renal disease, cardiovascular events, and death. There is some evidence that [[angiotensin converting enzyme inhibitors]] (ACEIs) are superior to other inhibitors of the renin-angiotensin system such as [[angiotensin receptor blockers]] (ARBs), or [[aliskiren]] in preventing cardiovascular disease. Although a more recent review found similar effects of ACEIs and ARBs on major cardiovascular and renal outcomes. There is no evidence that combining ACEIs and ARBs provides additional benefits.

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==== Aspirin ====

The use of [[aspirin]] to prevent cardiovascular disease in diabetes is controversial. Aspirin is recommended by some in people at high risk of cardiovascular disease, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes. 2015 American Diabetes Association recommendations for aspirin use (based on expert consensus or clinical experience) are that low-dose aspirin use is reasonable in adults with diabetes who are at intermediate risk of cardiovascular disease (10-year cardiovascular disease risk, 5–10%). National guidelines for England and Wales by the [[National Institute for Health and Care Excellence]] (NICE) recommend against the use of aspirin in people with type 1 or type 2 diabetes who do not have confirmed cardiovascular disease.

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===Surgery===

[[Bariatric surgery|Weight loss surgery]] in those with [[obesity]] and type 2 diabetes is often an effective measure. Many are able to maintain normal blood sugar levels with little or no medications following surgery and long-term mortality is decreased. There is, however, a short-term mortality risk of less than 1% from the surgery. The [[body mass index]] cutoffs for when surgery is appropriate are not yet clear. It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.

A [[pancreas transplant]] is occasionally considered for people with type&nbsp;1 diabetes who have severe complications of their disease, including [[Chronic kidney disease|end stage kidney disease]] requiring [[kidney transplantation]].

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===Self-management and 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 in a team approach. Evidence has shown that social prescribing led to slight improvements in blood sugar control for people with type 2 diabetes. Home [[telehealth]] support can be an effective management technique.

The use of [[technology]] to deliver educational programs for adults with type 2 diabetes includes computer-based self-management interventions to collect for tailored responses to facilitate self-management. There is no adequate evidence to support effects on [[cholesterol]], [[blood pressure]], [[Behavior change (public health)|behavioral change]] (such as [[physical activity]] levels and dietary), [[Depression (mood)|depression]], weight and [[Quality of life (healthcare)|health-related quality of life]], nor in other biological, cognitive or emotional outcomes.

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==Epidemiology==

{{Main|Epidemiology of diabetes}}

[[File:Prevalence of Diabetes by Percent of Country Population (2014) Gradient Map.png|thumb|upright=1.4|Rates of diabetes worldwide in 2014. The worldwide prevalence was 9.2%.]]

[[File:Diabetes mellitus world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.4|Mortality rate of diabetes worldwide in 2012 per million inhabitants {{Div col|small=yes|colwidth=10em}}{{legend|#ffff20|28–91}}{{legend|#ffe820|92–114}}{{legend|#ffd820|115–141}}{{legend|#ffc020|142–163}}{{legend|#ffa020|164–184}}{{legend|#ff9a20|185–209}}{{legend|#f08015|210–247}}{{legend|#e06815|248–309}}{{legend|#d85010|310–404}}{{legend|#d02010|405–1879}}{{div col end}}]]

In 2017, 425&nbsp;million people had diabetes worldwide, up from an estimated 382&nbsp;million people in 2013 and from 108&nbsp;million in 1980. Accounting for the shifting age structure of the global population, the prevalence of diabetes is 8.8% among adults, nearly double the rate of 4.7% in 1980. Type&nbsp;2 makes up about 90% of the cases. Some data indicate rates are roughly equal in women and men, but male excess in diabetes has been found in many populations with higher type 2 incidence, possibly due to sex-related differences in insulin sensitivity, consequences of obesity and regional body fat deposition, and other contributing factors such as high blood pressure, tobacco smoking, and alcohol intake.

The WHO estimates that diabetes resulted in 1.5&nbsp;million deaths in 2012, making it the 8th leading cause of death. However another 2.2&nbsp;million deaths worldwide were attributable to high blood glucose and the increased risks of cardiovascular disease and other associated complications (e.g. kidney failure), which often lead to premature death and are often listed as the underlying cause on death certificates rather than diabetes. For example, in 2017, the [[International Diabetes Federation]] (IDF) estimated that diabetes resulted in 4.0&nbsp;million deaths worldwide, using modeling to estimate the total number of deaths that could be directly or indirectly attributed to diabetes.

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==History==

{{Main|History of diabetes}}

Diabetes was one of the first diseases described, with an [[Ancient Egypt|Egyptian]] manuscript from {{Abbr|c.|circa}} 1500 [[Common Era|BCE]] mentioning "too great emptying of the urine." The [[Ebers papyrus]] includes a recommendation for a drink to take in such cases. The first described cases are believed to have been type&nbsp;1 diabetes. Indian physicians around the same time identified the disease and classified it as ''madhumeha'' or "honey urine", noting the urine would attract ants.

The term "diabetes" or "to pass through" was first used in 230&nbsp;BCE by the Greek [[Apollonius (physician)|Apollonius of Memphis]]. The disease was considered rare during the time of the [[Roman empire]], with [[Galen]] commenting he had only seen two cases during his career. This is possibly due to the diet and lifestyle of the ancients, or because the clinical symptoms were observed during the advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea urinosa).

The earliest surviving work with a detailed reference to diabetes is that of [[Aretaeus of Cappadocia]] (2nd or early 3rd{{nbsp}}century CE). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness, reflecting the beliefs of the "[[Pneumatic school|Pneumatic School]]". He hypothesized a correlation between diabetes and other diseases, and he discussed differential diagnosis from the snakebite, which also provokes excessive thirst. His work remained unknown in the West until 1552, when the first Latin edition was published in Venice.

Two types of diabetes were identified as separate conditions for the first time by the Indian physicians [[Sushruta]] and [[Charaka]] in 400–500&nbsp;CE with one type being associated with youth and another type with being overweight. Effective treatment was not developed until the early part of the 20th century when Canadians [[Frederick Banting]] and [[Charles Best (medical scientist)|Charles Best]] isolated and purified insulin in 1921 and 1922. This was followed by the development of the long-acting insulin [[NPH insulin|NPH]] in the 1940s.

===Etymology===

The word ''diabetes'' ({{IPAc-en|ˌ|d|aɪ|.|ə|ˈ|b|iː|t|iː|z}} or {{IPAc-en|ˌ|d|aɪ|.|ə|ˈ|b|iː|t|ᵻ|s}}) comes from [[Latin]] ''diabētēs'', which in turn comes from [[Ancient Greek]] [[wikt:διαβήτης|διαβήτης]] (''diabētēs''), which literally means "a passer through; a [[siphon]]". [[Ancient Greece|Ancient Greek]] [[physician]] [[Aretaeus of Cappadocia]] ([[Floruit|fl.]] 1st{{nbsp}}century [[Common Era|CE]]) used that word, with the intended meaning "excessive discharge of urine", as the name for the disease. Ultimately, the word comes from Greek διαβαίνειν (''diabainein''), meaning "to pass through", which is composed of δια- (''dia''-), meaning "through" and βαίνειν (''bainein''), meaning "to go". The word "diabetes" is first recorded in English, in the form ''diabete'', in a medical text written around 1425.

The word ''[[wikt:mellitus|mellitus]]'' ({{IPAc-en|m|ə|ˈ|l|aɪ|t|ə|s}} or {{IPAc-en|ˈ|m|ɛ|l|ᵻ|t|ə|s}}) comes from the classical Latin word ''mellītus'', meaning "mellite" (i.e. sweetened with honey; honey-sweet). The Latin word comes from ''mell''-, which comes from ''mel'', meaning "honey"; sweetness; pleasant thing, and the suffix -''ītus'', whose meaning is the same as that of the English suffix "-ite". It was [[Thomas Willis]] who in 1675 added "mellitus" to the word "diabetes" as a designation for the disease, when he noticed the urine of a person with diabetes had a sweet taste (glycosuria). This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and [[Persian people|Persians]].

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==Society and culture==

{{Further|List of films featuring diabetes}}

The 1989 "[[St. Vincent Declaration]]" was the result of international efforts to improve the care accorded to those with diabetes. Doing so is important not only in terms of quality of life and life expectancy but also economically{{snd}}expenses due to diabetes have been shown to be a major drain on health{{snd}}and productivity-related resources for healthcare systems and governments.

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=== Diabetes stigma ===

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=== Racial and economic inequalities ===

People with diabetes who have neuropathic symptoms such as numbness or tingling in feet or hands are twice as likely to be [[unemployed]] as those without the symptoms.

In 2010, diabetes-related emergency room (ER) visit rates in the United States were higher among people from the lowest income communities (526 per 10,000 population) than from the highest income communities (236 per 10,000 population). Approximately 9.4% of diabetes-related ER visits were for the uninsured.

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===Naming===

Diabetes mellitus is also occasionally known as "sugar diabetes" to differentiate it from [[diabetes insipidus]].

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==Other animals==

{{main|Diabetes in dogs|Diabetes in cats}}

In animals, diabetes is most commonly encountered in dogs and cats. Middle-aged animals are most commonly affected. Female dogs are twice as likely to be affected as males, while according to some sources, male cats are more prone than females. In both species, all breeds may be affected, but some small dog breeds are particularly likely to develop diabetes, such as [[Poodle|Miniature Poodles]].

Feline diabetes is strikingly similar to human type 2 diabetes. The [[Burmese cat|Burmese]], [[Russian Blue]], [[Abyssinian cat|Abyssinian]], and [[Norwegian Forest cat|Norwegian Forest]] cat breeds are at higher risk than other breeds. Overweight cats are also at higher risk.

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== See also ==

* [[Outline of diabetes]]

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== External links ==

{{Diabetes}}

{{Disease of the pancreas and glucose metabolism}}