Diabetes

Diabetes mellitus (DM), commonly known as just diabetes, is

a group of metabolic disorders characterized by a high blood
Diabetes mellitus
sugar level over a prolonged period of time.[11] Symptoms often
include frequent urination, increased thirst and increased
appetite.[2] If left untreated, diabetes can cause many health
complications.[2] Acute complications can include diabetic
ketoacidosis, hyperosmolar hyperglycemic state, or death.[3]
Serious long-term complications include cardiovascular disease,
stroke, chronic kidney disease, foot ulcers, damage to the
nerves, damage to the eyes and cognitive impairment.[2][5]

Diabetes is due to either the pancreas not producing enough

insulin, or the cells of the body not responding properly to the
Universal blue circle symbol for
insulin produced.[12] There are three main types of diabetes
diabetes.[1]
mellitus:[2]
Pronunciation /ˌdaɪ əˈbi tiz, -tɪs/
Type 1 diabetes results from failure of the pancreas to /ˈmɛl ɪ təs, məˈlaɪ-/
produce enough insulin due to loss of beta cells.[2]
This form was previously referred to as "insulin- Specialty Endocrinology
dependent diabetes mellitus" (IDDM) or "juvenile Symptoms Frequent urination,
diabetes".[2] The loss of beta cells is caused by an increased thirst,
autoimmune response.[13] The cause of this increased hunger[2]
autoimmune response is unknown.[2]
Complications Diabetic
Type 2 diabetes begins with insulin resistance, a
ketoacidosis,
condition in which cells fail to respond to insulin
properly.[2] As the disease progresses, a lack of hyperosmolar
insulin may also develop.[14] This form was previously hyperglycemic state,
referred to as "non insulin-dependent diabetes heart disease,
mellitus" (NIDDM) or "adult-onset diabetes".[2] The stroke, pain/pins and
most common cause is a combination of excessive needles in hands
body weight and insufficient exercise.[2] and/or feet, chronic
Gestational diabetes is the third main form, and kidney failure, foot
occurs when pregnant women without a previous ulcers, cognitive
history of diabetes develop high blood sugar levels.[2] impairment,
gastroparesis[2][3][4][5]
Type 1 diabetes must be managed with insulin injections.[2]
Prevention and treatment of type 2 diabetes involves maintaining Risk factors Type 1: Family
a healthy diet, regular physical exercise, a normal body weight, history[6]
and avoiding use of tobacco.[2] Type 2 diabetes may be treated Type 2: Obesity, lack
with medications such as insulin sensitizers with or without of exercise,
insulin.[15] Control of blood pressure and maintaining proper genetics[2][7]
foot and eye care are important for people with the disease.[2] Diagnostic High blood sugar[2]
Insulin and some oral medications can cause low blood
method
sugar.[16] Weight loss surgery in those with obesity is sometimes
Treatment Healthy diet, physical
an effective measure in those with type 2 diabetes.[17] exercise[2]
Gestational diabetes usually resolves after the birth of the Medication Insulin, anti-diabetic
baby.[18] medication like
As of 2019, an estimated 463 million people had diabetes metformin[2][8][9]
worldwide (8.8% of the adult population), with type 2 diabetes Frequency 463 million (8.8%)[10]
making up about 90% of the cases.[10] Rates are similar in Deaths 4.2 million (2019)[10]
women and men.[19] Trends suggest that rates will continue to
rise.[10] Diabetes at least doubles a person's risk of early death.[2] In 2019, diabetes resulted in
approximately 4.2 million deaths.[10] It is the 7th leading cause of death globally.[20][21] The global
economic cost of diabetes-related health expenditure in 2017 was estimated at US$727 billion.[10] In the
United States, diabetes cost nearly US$327 billion in 2017.[22] Average medical expenditures among
people with diabetes are about 2.3 times higher.[23]

Contents
Signs and symptoms
Diabetic emergencies
Complications
Causes
Type 1
Type 2
Gestational diabetes
Other types
Pathophysiology
Diagnosis
Prevention
Management
Lifestyle
Medications
Surgery
Support
Epidemiology
History
Etymology
Society and culture
Naming
Other animals
Research
Major clinical trials
References
External links
Signs and symptoms
The classic symptoms of untreated diabetes are
unintended weight loss, polyuria (increased
urination), polydipsia (increased thirst), and
polyphagia (increased hunger).[24] Symptoms
may develop rapidly (weeks or months) in type 1
diabetes, while they usually develop much more
slowly and may be subtle or absent in type 2
diabetes.[25]

Several other signs and symptoms can mark the

onset of diabetes although they are not specific to
the disease. In addition to the known symptoms
listed above, they include blurred vision,
headache, fatigue, slow healing of cuts, and itchy
skin. Prolonged high blood glucose can cause
glucose absorption in the lens of the eye, which
leads to changes in its shape, resulting in vision
changes. Long-term vision loss can also be
caused by diabetic retinopathy. A number of skin Overview of the most significant symptoms of diabetes
rashes that can occur in diabetes are collectively
known as diabetic dermadromes.[26]

Diabetic emergencies

People with diabetes (usually but not exclusively in type 1 diabetes) may also experience diabetic
ketoacidosis (DKA), a metabolic disturbance characterized by nausea, vomiting and abdominal pain, the
smell of acetone on the breath, deep breathing known as Kussmaul breathing, and in severe cases a
decreased level of consciousness. DKA requires emergency treatment in hospital.[27] A rarer but more
dangerous condition is hyperosmolar hyperglycemic state (HHS), which is more common in type 2
diabetes and is mainly the result of dehydration caused by high blood sugars.[27]

Treatment-related low blood sugar (hypoglycemia) is common in people with type 1 and also type 2
diabetes depending on the medication being used. Most cases are mild and are not considered medical
emergencies. Effects can range from feelings of unease, sweating, trembling, and increased appetite in mild
cases to more serious effects such as confusion, changes in behavior such as aggressiveness, seizures,
unconsciousness, and rarely permanent brain damage or death in severe cases.[28][29] Rapid breathing,
sweating, and cold, pale skin are characteristic of low blood sugar but not definitive.[30] Mild to moderate
cases are self-treated by eating or drinking something high in rapidly absorbed carbohydrates. Severe cases
can lead to unconsciousness and must be treated with intravenous glucose or injections with glucagon.[31]

Complications

All forms of diabetes increase the risk of long-term complications. These typically develop after many years
(10–20) but may be the first symptom in those who have otherwise not received a diagnosis before that
time.
The major long-term complications relate to damage to blood
vessels. Diabetes doubles the risk of cardiovascular disease[32] and
about 75% of deaths in people with diabetes are due to coronary
artery disease.[33] Other macrovascular diseases include stroke,
and peripheral artery disease.

The primary complications of diabetes due to damage in small

blood vessels include damage to the eyes, kidneys, and nerves.[34] Retinopathy, nephropathy, and
Damage to the eyes, known as diabetic retinopathy, is caused by neuropathy are potential
damage to the blood vessels in the retina of the eye, and can result complications of diabetes
in gradual vision loss and eventual blindness.[34] Diabetes also
increases the risk of having glaucoma, cataracts, and other eye
problems. It is recommended that people with diabetes visit an eye doctor once a year.[35] Damage to the
kidneys, known as diabetic nephropathy, can lead to tissue scarring, urine protein loss, and eventually
chronic kidney disease, sometimes requiring dialysis or kidney transplantation.[34] Damage to the nerves of
the body, known as diabetic neuropathy, is the most common complication of diabetes.[34] The symptoms
can include numbness, tingling, pain, and altered pain sensation, which can lead to damage to the skin.
Diabetes-related foot problems (such as diabetic foot ulcers) may occur, and can be difficult to treat,
occasionally requiring amputation. Additionally, proximal diabetic neuropathy causes painful muscle
atrophy and weakness.

There is a link between cognitive deficit and diabetes. Compared to those without diabetes, those with the
disease have a 1.2 to 1.5-fold greater rate of decline in cognitive function.[36] Having diabetes, especially
when on insulin, increases the risk of falls in older people.[37]

Causes
Diabetes mellitus is classified into six Comparison of type 1 and 2 diabetes[38]
categories: type 1 diabetes, type 2
Feature Type 1 diabetes Type 2 diabetes
diabetes, hybrid forms of diabetes,
hyperglycemia first detected during Onset Sudden Gradual
pregnancy, "unclassified diabetes", and Age at onset Mostly in children Mostly in adults
"other specific types".[40] The "hybrid
forms of diabetes" contains slowly Body size Thin or normal[39] Often obese
evolving, immune-mediated diabetes of Ketoacidosis Common Rare
adults and ketosis-prone type 2 diabetes.
Autoantibodies Usually present Absent
The "hyperglycemia first detected during
pregnancy" contains gestational diabetes Endogenous insulin Low or absent Normal, decreased
or increased
mellitus and diabetes mellitus in
pregnancy (type 1 or type 2 diabetes first Concordance
50% 90%
diagnosed during pregnancy). The "other in identical twins
specific types" are a collection of a few Prevalence ~10% ~90%
dozen individual causes. Diabetes is a
more variable disease than once thought and people may have combinations of forms.[41] The term
"diabetes", without qualification, refers to diabetes mellitus.[42]

Type 1
Type 1 diabetes is characterized by loss of the insulin-producing beta cells of the pancreatic islets, leading
to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of
type 1 diabetes is of an immune-mediated nature, in which a T cell-mediated autoimmune attack leads to
the loss of beta cells and thus insulin.[43] It 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. Although
it has been called "juvenile diabetes" due to the frequent onset in children, the majority of individuals living
with type 1 diabetes are now adults.[6]

"Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to
describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in
insulin-dependent diabetes. This term, however, has no biologic basis and should not be used.[44] Still,
type 1 diabetes can be accompanied by irregular and unpredictable high blood sugar levels, and the
potential for diabetic ketoacidosis or serious low blood sugar levels. Other complications include an
impaired counterregulatory response to low blood sugar, infection, gastroparesis (which leads to erratic
absorption of dietary carbohydrates), and endocrinopathies (e.g., Addison's disease).[44] These phenomena
are believed to occur no more frequently than in 1% to 2% of persons with type 1 diabetes.[45]

Type 1 diabetes is partly inherited, with multiple genes, including

certain HLA genotypes, known to influence the risk of diabetes. In
genetically susceptible people, the onset of diabetes can be
triggered by one or more environmental factors,[46] 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.[46][47] Among dietary factors, data suggest that gliadin (a
protein present in gluten) may play a role in the development of Autoimmune attack in type 1
type 1 diabetes, but the mechanism is not fully understood.[48][49] diabetes.

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.[50]

Type 2

Type 2 diabetes is characterized by insulin resistance, which may

be combined with relatively reduced insulin secretion.[12] 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.[2] Many people with type 2 diabetes have Reduced insulin secretion and
evidence of prediabetes (impaired fasting glucose and/or impaired absorption leads to high glucose
glucose tolerance) before meeting the criteria for type 2 content in the blood.
diabetes.[51] The progression of prediabetes to overt type 2
diabetes can be slowed or reversed by lifestyle changes or
medications that improve insulin sensitivity or reduce the liver's glucose production.[52]
Type 2 diabetes is primarily due to lifestyle factors and genetics.[53] 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, stress, and urbanization.[38] 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.[12] Even those who are
not obese may have a high waist–hip ratio.[12]

Dietary factors such as sugar-sweetened drinks are associated with an increased risk.[54][55] The type of
fats in the diet is also important, with saturated fat and trans fats increasing the risk and polyunsaturated and
monounsaturated fat decreasing the risk.[53] Eating white rice excessively may increase the risk of diabetes,
especially in Chinese and Japanese people.[56] Lack of physical activity may increase the risk of diabetes in
some people.[57]

Adverse childhood experiences (ACEs), including abuse, neglect, and household difficulties, increase the
likelihood of type 2 diabetes later in life by 32%, with neglect having the strongest effect.[58]

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 pregnancies and may
improve or disappear after delivery.[59] It is recommended that all pregnant women get tested starting
around 24–28 weeks gestation.[60] 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.[60] However, after pregnancy
approximately 5–10% of women with gestational diabetes are found to have another form of diabetes, most
commonly type 2.[59] 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.[61]

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 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 high blood bilirubin level 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 caesarean section may be performed if there is marked fetal distress[62]or an increased
risk of injury associated with macrosomia, such as shoulder dystocia.[63]

Other types

Maturity onset diabetes of the young (MODY) is a rare autosomal dominant inherited form of diabetes, due
to one of several single-gene mutations causing defects in insulin production.[64] 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.[65]

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, whereas others increase insulin resistance (especially glucocorticoids which
can provoke "steroid diabetes"). The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes
mellitus (MRDM or MMDM, ICD-10 code E12), was deprecated by the World Health Organization
(WHO) when the current taxonomy was introduced in 1999.[66] 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.[67] It was first discovered in 1990 or 1991.

The following is a list of disorders that may increase the risk of diabetes:[68]

Genetic defects of β-cell function Endocrinopathies

Maturity onset diabetes of the young Growth hormone excess (acromegaly)
Mitochondrial DNA mutations Cushing syndrome
Genetic defects in insulin processing or Hyperthyroidism
insulin action Hypothyroidism
Defects in proinsulin conversion Pheochromocytoma
Insulin gene mutations Glucagonoma
Insulin receptor mutations Infections
Exocrine pancreatic defects Cytomegalovirus infection
Chronic pancreatitis Coxsackievirus B
Pancreatectomy Drugs
Pancreatic neoplasia Glucocorticoids
Cystic fibrosis Thyroid hormone
Hemochromatosis β-adrenergic agonists
Fibrocalculous pancreatopathy Statins[69]

Pathophysiology
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 receptors play a central role in all forms of
diabetes mellitus.[70]

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.[71] 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.[71]

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.[72]

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 synthesis, and
other metabolic derangements, such as metabolic
acidosis in cases of complete insulin deficiency.[71]
The fluctuation of blood sugar (red) and the sugar-
When glucose concentration in the blood remains lowering hormone insulin (blue) in humans during the
high over time, the kidneys reach a threshold of course of a day with three meals. One of the effects
reabsorption, and the body excretes glucose in the of a sugar-rich vs a starch-rich meal is highlighted.
urine (glycosuria).[73] 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).[71] In
addition, intracellular glucose deficiency stimulates
appetite leading to excessive food intake
(polyphagia).[74]

Diagnosis
Mechanism of insulin release in normal pancreatic
Diabetes mellitus is diagnosed with a test for the beta cells. Insulin production is more or less
glucose content in the blood, and is diagnosed by constant within the beta cells. Its release is triggered
demonstrating any one of the following:[66] by food, chiefly food containing absorbable glucose.

Fasting plasma glucose level ≥ 7.0 mmol/L

(126 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.
Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) two hours after a 75 gram oral glucose load as
in a glucose tolerance test (OGTT)
Symptoms of high blood sugar and plasma glucose ≥ 11.1 mmol/L (200 mg/dL) either while
fasting or not fasting
Glycated hemoglobin (HbA1C) ≥ 48 mmol/mol (≥ 6.5 DCCT %).[75]

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.[78] According to the
current definition, two fasting glucose measurements above 7.0 mmol/L (126 mg/dL) is considered
diagnostic for diabetes mellitus.
Per the
WHO, WHO diabetes diagnostic criteria[76][77]
people with Condition 2-hour glucose Fasting glucose HbA1c
fasting
glucose Unit mmol/L mg/dL mmol/L mg/dL mmol/mol DCCT %
levels from Normal < 7.8 < 140 < 6.1 < 110 < 42 < 6.0
6.1 to
Impaired fasting glycaemia < 7.8 < 140 6.1–7.0 110–125 42–46 6.0–6.4
6.9 mmol/L
(110 to Impaired glucose tolerance ≥ 7.8 ≥ 140 < 7.0 < 126 42–46 6.0–6.4
125 mg/dL) Diabetes mellitus ≥ 11.1 ≥ 200 ≥ 7.0 ≥ 126 ≥ 48 ≥ 6.5
are
considered to
have impaired fasting glucose.[79] People with plasma glucose at or above 7.8 mmol/L (140 mg/dL), but
not over 11.1 mmol/L (200 mg/dL), two hours after a 75 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.[80] The American Diabetes
Association (ADA) since 2003 uses a slightly different range for impaired fasting glucose of 5.6 to
6.9 mmol/L (100 to 125 mg/dL).[81]

Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and
death from any cause.[82]

Prevention
There is no known preventive measure for type 1 diabetes.[2] Type 2 diabetes—which accounts for 85–
90% of all cases worldwide—can often be prevented or delayed[83] by maintaining a normal body weight,
engaging in physical activity, and eating a healthy diet.[2] Higher levels of physical activity (more than 90
minutes per day) reduce the risk of diabetes by 28%.[84] Dietary changes known to be effective in helping
to prevent diabetes include maintaining a diet rich in whole grains and fiber, and choosing good fats, such
as the polyunsaturated fats found in nuts, vegetable oils, and fish.[85] Limiting sugary beverages and eating
less red meat and other sources of saturated fat can also help prevent diabetes.[85] 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.[86]

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.[87]

Management
Diabetes management concentrates on keeping blood sugar levels as close to normal, without causing low
blood sugar. This can usually be accomplished with dietary changes, exercise, weight loss, and use of
appropriate medications (insulin, oral medications).

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.[88][89] Per the
American College of Physicians, the goal of treatment is an HbA1C level of 7-8%.[90] Attention is also paid
to other health problems that may accelerate the negative effects of diabetes. These include smoking, high
blood pressure, metabolic syndrome obesity, and lack of regular exercise.[91] Specialized footwear is
widely used to reduce the risk of ulcers in at-risk diabetic feet although evidence for the efficacy of this
remains equivocal.[92]

Lifestyle

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 within acceptable
bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are
recommended to control blood pressure.[93][94]

Weight loss can prevent progression from prediabetes to diabetes type 2, decrease the risk of cardiovascular
disease, or result in a partial remission in people with diabetes.[95][96] No single dietary pattern is best for
all people with diabetes.[97] 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.[95][96]
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 or very-low
carbohydrate diets are a viable approach.[96] For overweight people with type 2 diabetes, any diet that
achieves weight loss is effective.[97][98]

Medications

Glucose control

Most medications used to treat diabetes act by lowering 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 kidney
problems or eye problems.[99][100] 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.[101]

There are a number of different classes of anti-diabetic medications. Type 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.[102] Type 2 diabetes is generally taken with
medication that is taken by mouth (e.g. metformin) although some eventually require injectable treatment
with insulin or GLP-1 agonists.[103]

Metformin is generally recommended as a first-line treatment for type 2 diabetes, as there is good evidence
that it decreases mortality.[8] It works by decreasing the liver's production of glucose.[104] Several other
groups of drugs, mostly given by mouth, may also decrease blood sugar in type 2 diabetes. These include
agents that increase insulin release (sulfonylureas), 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 inhibitors).[104] When insulin is used
in type 2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications.[8]
Doses of insulin are then increased until glucose targets are reached.[8][105]

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 mmHg for people with
diabetes.[106] 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,[107] 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.[108]

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.[109] 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),[110] or aliskiren in preventing cardiovascular disease.[111] Although
a more recent review found similar effects of ACEIs and ARBs on major cardiovascular and renal
outcomes.[112] There is no evidence that combining ACEIs and ARBs provides additional benefits.[112]

Aspirin

The use of aspirin to prevent cardiovascular disease in diabetes is controversial.[109] 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.[113] 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%).[109] 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.[102][103]

Surgery

Weight loss surgery in those with obesity and type 2 diabetes is often an effective measure.[17] Many are
able to maintain normal blood sugar levels with little or no medications following surgery[114] and long-
term mortality is decreased.[115] There is, however, a short-term mortality risk of less than 1% from the
surgery.[116] The body mass index cutoffs for when surgery is appropriate are not yet clear.[115] It is
recommended that this option be considered in those who are unable to get both their weight and blood
sugar under control.[117]

A pancreas transplant is occasionally considered for people with type 1 diabetes who have severe
complications of their disease, including end stage kidney disease requiring kidney transplantation.[118]

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. Home telehealth support can be an effective management technique.[119]

Epidemiology
In 2017, 425 million people had diabetes
worldwide,[120] up from an estimated 382 million
people in 2013[121] and from 108 million in
1980.[122] 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.[120][122] Type 2 makes up about 90%
of the cases.[19][38] Some data indicate rates are
roughly equal in women and men,[19] but male
excess in diabetes has been found in many Rates of diabetes worldwide in 2014. The worldwide
populations with higher type 2 incidence, possibly prevalence was 9.2%.
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.[123][124]

The WHO estimates that diabetes resulted in

1.5 million deaths in 2012, making it the 8th leading
cause of death.[15][122] However another 2.2 million
deaths worldwide were attributable to high blood
glucose and the increased risks of cardiovascular Mortality rate of diabetes worldwide in 2012 per
disease and other associated complications (e.g. million inhabitants
kidney failure), which often lead to premature death 28–91 164–184 310–404
and are often listed as the underlying cause on death 92–114 185–209 405–1879
certificates rather than diabetes.[122][125] For 115–141 210–247
example, in 2017, the International Diabetes 142–163 248–309
Federation (IDF) estimated that diabetes resulted in
4.0 million deaths worldwide,[120] using modeling
to estimate the total number of deaths that could be
directly or indirectly attributed to diabetes.[120]

Diabetes occurs throughout the world but is more common (especially type 2) in more developed countries.
The greatest increase in rates has however been seen in low- and middle-income countries,[122] where
more than 80% of diabetic deaths occur.[126] The fastest prevalence increase is expected to occur in Asia
and Africa, where most people with diabetes will probably live in 2030.[127] The increase in rates in
developing countries follows the trend of urbanization and lifestyle changes, including increasingly
sedentary lifestyles, less physically demanding work and the global nutrition transition, marked by
increased intake of foods that are high energy-dense but nutrient-poor (often high in sugar and saturated
fats, sometimes referred to as the "Western-style" diet).[122][127] The global number of diabetes cases might
increase by 48% between 2017 and 2045.[120]

History
Diabetes was one of the first diseases described,[128] with an Egyptian manuscript from c. 1500 BCE
mentioning "too great emptying of the urine."[129] The Ebers papyrus includes a recommendation for a
drink to take in such cases.[130] The first described cases are believed to have been type 1 diabetes.[129]
Indian physicians around the same time identified the disease and classified it as madhumeha or "honey
urine", noting the urine would attract ants.[129][130]
The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Apollonius of
Memphis.[129] The disease was considered rare during the time of the Roman empire, with Galen
commenting he had only seen two cases during his career.[129] 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).[131]

The earliest surviving work with a detailed reference to diabetes is that of Aretaeus of Cappadocia (2nd or
early 3rd century CE). He described the symptoms and the course of the disease, which he attributed to the
moisture and coldness, reflecting the beliefs of the "Pneumatic School". He hypothesized a correlation
between diabetes and other diseases, and he discussed differential diagnosis from the snakebite, which also
provokes excessive thirst. His work remained unknown in the West until 1552, when the first Latin edition
was published in Venice.[131]

Two types of diabetes were identified as separate conditions for the first time by the Indian physicians
Sushruta and Charaka in 400–500 CE with one type being associated with youth and another type with
being overweight.[129] Effective treatment was not developed until the early part of the 20th century when
Canadians Frederick Banting and Charles Herbert Best isolated and purified insulin in 1921 and 1922.[129]
This was followed by the development of the long-acting insulin NPH in the 1940s.[129]

Etymology

The word diabetes (/ˌdaɪ.əˈbiːtiːz/ or /ˌdaɪ.əˈbiːtɪs/) comes from Latin diabētēs, which in turn comes from
Ancient Greek διαβήτης (diabētēs), which literally means "a passer through; a siphon".[132] Ancient Greek
physician Aretaeus of Cappadocia (fl. 1st century CE) used that word, with the intended meaning
"excessive discharge of urine", as the name for the disease.[133][134] Ultimately, the word comes from
Greek διαβαίνειν (diabainein), meaning "to pass through,"[132] which is composed of δια- (dia-), meaning
"through" and βαίνειν (bainein), meaning "to go".[133] The word "diabetes" is first recorded in English, in
the form diabete, in a medical text written around 1425.

The word mellitus (/məˈlaɪtəs/ or /ˈmɛlɪtəs/) comes from the classical Latin word mellītus, meaning
"mellite"[135] (i.e. sweetened with honey;[135] honey-sweet[136]). The Latin word comes from mell-, which
comes from mel, meaning "honey";[135][136] sweetness;[136] pleasant thing,[136] and the suffix -ītus,[135]
whose meaning is the same as that of the English suffix "-ite".[137] 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 Persians.

Society and culture

The 1989 "St. Vincent Declaration"[138][139] 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 – 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.[140]

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.[141]
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.[142]

Naming

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 noninsulin-
dependent diabetes mellitus (NIDDM). Beyond these two types, there is no agreed-upon standard
nomenclature.[143]

Diabetes mellitus is also occasionally known as "sugar diabetes" to differentiate it from diabetes
insipidus.[144]

Other animals
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 Miniature Poodles.[145]

Feline diabetes is strikingly similar to human type 2 diabetes. The Burmese, Russian Blue, Abyssinian, and
Norwegian Forest cat breeds are at higher risk than other breeds. Overweight cats are also at higher
risk.[146]

The symptoms may relate to fluid loss and polyuria, but the course may also be insidious. Diabetic animals
are more prone to infections. The long-term complications recognized in humans are much rarer in animals.
The principles of treatment (weight loss, oral antidiabetics, subcutaneous insulin) and management of
emergencies (e.g. ketoacidosis) are similar to those in humans.[145]

Research
Inhalable insulin has been developed.[147] The original products were withdrawn due to side effects.
Afrezza, under development by the pharmaceuticals company MannKind Corporation, was approved by
the United States Food and Drug Administration (FDA) for general sale in June 2014.[148] An advantage
to inhaled insulin is that it may be more convenient and easy to use.[149]

Transdermal insulin in the form of a cream has been developed and trials are being conducted on people
with type 2 diabetes.[150][151]

Major clinical trials

The Diabetes Control and Complications Trial (DCCT) was a clinical study conducted by the United States
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) that was published in the New
England Journal of Medicine in 1993. Test subjects all had type 1 diabetes and were randomized to a tight
glycemic arm and a control arm with the standard of care at the time; people were followed for an average
of seven years, and people in the treatment had dramatically lower rates of diabetic complications. It was as
a landmark study at the time, and significantly changed the management of all forms of
diabetes.[101][152][153]

The United Kingdom Prospective Diabetes Study (UKPDS) was a clinical study conducted by Z that was
published in The Lancet in 1998. Around 3,800 people with type 2 diabetes were followed for an average
of ten years, and were treated with tight glucose control or the standard of care, and again the treatment arm
had far better outcomes. This confirmed the importance of tight glucose control, as well as blood pressure
control, for people with this condition.[101][154][155]

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External links
Diabetes (https://curlie.org/Health/Conditions_and_Disea Classification ICD-10: E10 (http D
ses/Endocrine_Disorders/Pancreas/Diabetes/) at Curlie s://icd.who.int/brow
American Diabetes Association (http://www.diabetes.org) se10/2019/en#/E1
IDF Diabetes Atlas (http://www.diabetesatlas.org/) 0)–E14 (https://icd.
National Diabetes Education Program (http://ndep.nih.go who.int/browse10/2
v/) 019/en#/E14) ·
ADA's Standards of Medical Care in Diabetes 2019 (http:// ICD-9-CM: 250 (htt
care.diabetesjournals.org/content/42/Supplement_1)
p://www.icd9data.c
Polonsky KS (October 2012). "The past 200 years in
om/getICD9Code.a
diabetes". The New England Journal of Medicine. 367
(14): 1332–40. doi:10.1056/NEJMra1110560 (https://doi.or shx?icd9=250) ·
 g/10.1056%2FNEJMra1110560). PMID 23034021 (https:// MeSH: D003920 (h
pubmed.ncbi.nlm.nih.gov/23034021). S2CID 9456681 (htt ttps://www.nlm.nih.
ps://api.semanticscholar.org/CorpusID:9456681). gov/cgi/mesh/2015/
"Diabetes" (https://medlineplus.gov/diabetes.html). MB_cgi?field=uid&t
MedlinePlus. U.S. National Library of Medicine.
erm=D003920)
External MedlinePlus:
resources 001214 (https://ww
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c134.htm#) ·
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