Diabetes
mellitus
From Wikipedia, the free encyclopedia
Diabetes mellitus, or simply diabetes, is a group of metabolic
diseases in which a person has high blood sugar,
either because the pancreas does not produce enough insulin, or
because cells do not respond to the insulin that is produced.[2]
This high blood sugar produces the classical symptoms of polyuria (frequent
urination), polydipsia (increased thirst) and polyphagia
(increased hunger).
There are three main types of
diabetes mellitus (DM).
- Type 1
DM results from the body's
failure to produce insulin, and currently requires the person to inject
insulin or wear an insulin pump. This form was previously referred to as
"insulin-dependent diabetes mellitus" (IDDM) or "juvenile
diabetes".
- Type 2
DM results from insulin resistance, a condition in which cells fail to use insulin
properly, sometimes combined with an absolute insulin deficiency. This
form was previously referred to as non insulin-dependent diabetes mellitus
(NIDDM) or "adult-onset diabetes".
- The third main form, gestational
diabetes occurs when pregnant women
without a previous diagnosis of diabetes develop a high blood glucose
level. It may precede development of type 2 DM.
Other forms of diabetes mellitus
include congenital diabetes, which is due to genetic defects
of insulin secretion, cystic fibrosis-related
diabetes, steroid diabetes induced by high doses of glucocorticoids, and
several forms of monogenic diabetes.
Untreated, diabetes can cause many
complications. Acute complications include diabetic ketoacidosis and nonketotic
hyperosmolar coma. Serious long-term complications
include cardiovascular disease, chronic renal failure, and diabetic retinopathy (retinal damage). Adequate treatment of diabetes is thus
important, as well as blood pressure
control and lifestyle factors such as stopping smoking and
maintaining a healthy body weight.
All forms of diabetes have been
treatable since insulin became available in 1921, and type 2 diabetes may be
controlled with medications. Insulin and some oral medications can cause hypoglycemia
(low blood sugars), which can be dangerous if severe. Both types 1 and 2 are chronic conditions that 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.
Classification
Diabetes mellitus is classified into
four broad categories: type 1, type 2, gestational diabetes and "other specific types".[2]
The "other specific types" are a collection of a few dozen individual
causes.[2]
The term "diabetes", without qualification, usually refers to
diabetes mellitus. The rare disease diabetes insipidus has similar symptoms as diabetes mellitus, but without
disturbances in the sugar metabolism (insipidus means "without
taste" in Latin) and does not involve the same disease mechanisms.
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.
Type
1 diabetes
Type 1 diabetes mellitus is
characterized by loss of the insulin-producing beta cells
of the islets of Langerhans in the pancreas, leading to insulin deficiency. This type
can be further classified as immune-mediated or idiopathic. The majority of
type 1 diabetes is of the immune-mediated nature, in which beta cell loss
is a T-cell-mediated autoimmune
attack.[5]
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 a
majority of these diabetes cases were in children.
"Brittle" diabetes, also
known as unstable diabetes or labile diabetes, is a term that was traditionally
used to describe to 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.[6]
There are many reasons for type 1 diabetes to be accompanied by irregular
and unpredictable hyperglycemias, frequently with ketosis, and
sometimes serious hypoglycemias, including an impaired counterregulatory response to
hypoglycemia, occult infection, gastroparesis (which leads to erratic absorption
of dietary carbohydrates), and endocrinopathies (e.g., Addison's disease).[6]
These phenomena are believed to occur no more frequently than in 1% to 2% of
persons with type 1 diabetes.[7]
Type
2 diabetes
Type 2 diabetes mellitus is
characterized by insulin resistance, which may be combined with relatively reduced insulin
secretion.[2]
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.
In the early stage of type 2,
the predominant abnormality is reduced insulin sensitivity. At this stage,
hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose
production by the liver.
Gestational
diabetes
Gestational diabetes mellitus (GDM)
resembles type 2 diabetes in several respects, involving a combination of
relatively inadequate insulin secretion and responsiveness. It occurs in about
2%–5% of all pregnancies and may improve or disappear after delivery. Gestational
diabetes is fully treatable, but requires careful medical supervision
throughout the pregnancy. About 20%–50% of affected women develop type 2
diabetes later in life.
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 Caesarean 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 the number of American women entering pregnancy with pre-existing
diabetes is increasing. In fact, the rate of diabetes in expectant mothers has
more than doubled in the past six years.[8]
This is particularly problematic as diabetes raises the risk of complications
during pregnancy, as well as increasing the potential for the children of
diabetic mothers to become diabetic in the future.
Other
types
Prediabetes 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 DM. Many people destined to develop type 2 DM spend many years
in a state of prediabetes which has been termed "America's largest
healthcare epidemic."[9]:10–11
Latent
autoimmune diabetes of adults
(LADA) is a condition in which type 1 DM develops in adults. Adults with
LADA are frequently initially misdiagnosed as having type 2 DM, 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.[10]
Signs
and symptoms
The classic symptoms of untreated
diabetes are loss of weight, polyuria (frequent
urination), polydipsia (increased thirst) and polyphagia
(increased hunger).[11]
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.
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. Blurred vision is a common complaint
leading to a diabetes diagnosis. A number of skin rashes that can occur in
diabetes are collectively known as diabetic dermadromes.
Diabetic
emergencies
People (usually with type 1
diabetes) may also present with diabetic ketoacidosis, a state of metabolic dysregulation characterized by the
smell of acetone, a rapid,
deep breathing known as Kussmaul breathing, nausea, vomiting and abdominal pain,
and altered states of consciousness.
A rare but equally severe
possibility is hyperosmolar
nonketotic state, which is more common in
type 2 diabetes and is mainly the result of dehydration.
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.[12]
The main "macrovascular" diseases (related to atherosclerosis
of larger arteries) are ischemic heart disease (angina and myocardial infarction), stroke and peripheral
vascular disease.
Diabetes also damages the capillaries
(causes microangiopathy).[13]
Diabetic retinopathy, which affects blood vessel formation in the retina of the eye, can lead to visual symptoms including reduced
vision and potentially blindness. Diabetic nephropathy, the impact of diabetes on the kidneys, can lead to scarring changes in the kidney
tissue, loss of small or
progressively larger amounts of protein in the urine, and eventually chronic kidney disease requiring dialysis.
Another risk is diabetic neuropathy, the impact of diabetes on the nervous
system — most commonly causing numbness,
tingling and pain in the feet, and also increasing the risk of skin damage due
to altered sensation. Together with vascular disease in the legs, neuropathy
contributes to the risk of diabetes-related foot problems (such as diabetic foot ulcers) that can be difficult to treat and occasionally require amputation.
As well, proximal
diabetic neuropathy causes painful muscle wasting
and weakness.
Several studies suggest[14]
a link between cognitive deficit and diabetes. Compared to those without diabetes, the
research showed that those with the disease have a 1.2 to 1.5-fold greater rate
of decline in cognitive function, and are at greater risk.
Causes
The cause of diabetes depends on the
type.
Type 1 diabetes is partly
inherited, and then triggered by certain infections, with some evidence
pointing at Coxsackie B4 virus. A genetic element in individual susceptibility to some of
these triggers 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 DM seems to require an environmental trigger. The
onset of type 1 diabetes is unrelated to lifestyle.
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Pathophysiology
The fluctuation of blood sugar (red)
and the sugar-lowering hormone insulin (blue) in
humans during the course of a day with three meals - one of the effects of a sugar-rich vs a
starch-rich meal
is highlighted.
Mechanism of insulin release in
normal pancreatic beta cells - insulin production is more or less constant
within the beta cells. Its release is triggered by food, chiefly food
containing absorbable glucose.
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.
Insulin is also the principal
control signal for conversion of glucose to glycogen for
internal storage in liver and muscle cells. Lowered glucose levels result both
in the reduced release of insulin from the β-cells and in the reverse
conversion of glycogen to glucose when glucose levels fall. This is mainly
controlled by the hormone glucagon, which acts in the opposite manner to insulin. Glucose thus
forcibly produced from internal liver cell stores (as glycogen) re-enters the
bloodstream; muscle cells lack the necessary export mechanism. Normally, liver
cells do this when the level of insulin is low (which normally correlates with
low levels of blood glucose).
Higher insulin levels increase some anabolic
("building up") processes, such as cell growth and duplication, protein synthesis, and fat storage. Insulin (or its lack) is the principal signal in
converting many of the bidirectional processes of metabolism from a catabolic
to an anabolic direction, and vice versa. In particular, a low insulin
level is the trigger for entering or leaving ketosis (the fat-burning metabolic
phase).
If the amount of insulin available
is insufficient, if cells respond poorly to the effects of insulin (insulin
insensitivity or resistance), or if the insulin itself is defective, then
glucose will not have its usual effect, so it will not be absorbed properly by
those body cells that require it, nor will it be stored appropriately in the
liver and muscles. The net effect is persistent high levels of blood glucose,
poor protein synthesis, and other metabolic derangements, such as acidosis.
When the glucose concentration in
the blood is raised to about 9-10 mmol/L (except certain conditions, such
as pregnancy), beyond its renal threshold
(i.e. when glucose level surpasses the transport maximum
of glucose reabsorption), reabsorption
of glucose in the proximal renal tubuli is incomplete, and part of the glucose remains in the urine (glycosuria). This increases the osmotic pressure
of the urine and inhibits reabsorption of water by the kidney, resulting in
increased urine production (polyuria) and increased fluid loss. Lost blood volume will
be replaced osmotically from water held in body cells and other body
compartments, causing dehydration and increased thirst.
Diagnosis
Diabetes mellitus is characterized
by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any
one of the following:[10]
People with fasting glucose levels
from 110 to 125 mg/dl (6.1 to 6.9 mmol/l) are considered to have impaired
fasting glucose.[22]
Patients with plasma glucose at or above 140 mg/dL (7.8 mmol/L), but
not over 200 mg/dL (11.1 mmol/L), two hours after a 75 g oral
glucose load are considered to have impaired
glucose tolerance. Of these two prediabetic states,
the latter in particular is a major risk factor for progression to full-blown
diabetes mellitus, as well as cardiovascular disease.[23]
Glycated hemoglobin is better than fasting glucose
for determining risks of cardiovascular disease and death from any cause.[24]
Management
Diabetes mellitus is a chronic disease,
for which there is no known cure except in very specific situations. Management
concentrates on keeping blood sugar levels as close to normal
("euglycemia") as possible, without causing hypoglycemia. This can
usually be accomplished with diet, exercise, and use of appropriate medications
(insulin in the case of type 1 diabetes; oral medications, as well as
possibly insulin, in type 2 diabetes).
Patient education, understanding,
and participation is vital, since the complications of diabetes are far less
common and less severe in people who have well-managed blood sugar levels.[25][26]
The goal of treatment is an HbA1C level of 6.5%, but should not be lower than
that, and may be set higher.[27]
Attention is also paid to other health problems that may accelerate the
deleterious effects of diabetes. These include smoking, elevated cholesterol levels, obesity, high blood pressure,
and lack of regular exercise.[27]
Specialised footwear
is widely used to reduce the risk of ulceration, or re-ulceration, in at-risk
diabetic feet. Evidence for the efficacy of this remains equivocal, however.[28]
Lifestyle
There are roles for patient
education, dietetic support, sensible exercise, with the goal of keeping both
short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of
cardiovascular disease, lifestyle modifications are recommended to control
blood pressure.[29]
Medications
Oral medications
Metformin is generally recommended as a first line treatment for
type 2 diabetes, as there is good evidence that it decreases mortality.[30]
Routine use of aspirin, however, has not been found to improve outcomes in
uncomplicated diabetes.[31]
Insulin
Type 1 diabetes is typically
treated with a combinations of regular and NPH insulin, or
synthetic insulin analogs. When insulin is used in type 2 diabetes, a
long-acting formulation is usually added initially, while continuing oral
medications.[30]
Doses of insulin are then increased to effect.[30]
Support
In countries using a general practitioner system, such as the United Kingdom,
care may take place mainly outside hospitals, with hospital-based specialist
care used only in case of complications, difficult blood sugar control, or
research projects. In other circumstances, general practitioners and
specialists share care of a patient in a team approach. Home telehealth
support can be an effective management technique.[32]
Epidemiology
Globally, as of 2010, an estimated 285 million people had diabetes, with
type 2 making up about 90% of the cases.[3]
Its incidence is increasing rapidly, and by 2030, this number is estimated to
almost double.[33]
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.[33]
The increase in incidence 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.[33]
Australia
Indigenous populations in first
world countries have a higher prevalence and increasing incidence of diabetes
than their corresponding nonindigenous populations. In Australia, the
age-standardised prevalence of self-reported diabetes in indigenous Australians
is almost four times that of nonindigenous Australians.[34]
Preventative community health programs, such as Sugar
Man (diabetes education), are
showing some success in tackling this problem.
China
Almost one Chinese adult in ten has
diabetes. A 2010 study estimated that more than 92 million Chinese adults have
the disease, with another 150 million showing early symptoms.[35]
The incidence of the disease is increasing rapidly; a 2009 study found a 30%
increase in 7 years.[36]
India
India has more diabetics than any
other country in the world, according to the International Diabetes Foundation,[37]
although more recent data suggest that China has even more.[35]
The disease affects more than 50 million Indians - 7.1% of the nation's adults
- and kills about 1 million Indians a year.[37]
The average age on onset is 42.5 years.[37]
The high incidence is attributed to a combination of genetic susceptibility
plus adoption of a high-calorie, low-activity lifestyle by India's growing
middle class.[38]
United
Kingdom
About 3.8 million people in the
United Kingdom have diabetes mellitus, but the charity Diabetes U.K. have
made predictions that that could become high as 6.2 million by 2035/2036.
Diabetes U.K. have also predicted that the National Health Service could be spending as much as 16.9 billion pounds on
diabetes mellitus by 2035, a figure that means the NHS could be spending as
much as 17% of its budget on diabetes treatment by 2035.[39][40][41]
United
States
For at least 20 years, diabetes
rates in North America have been increasing substantially. In 2010, nearly 26 million
people have diabetes in the United States, of whom 7 million people remain
undiagnosed. Another 57 million people are estimated to have prediabetes.[42][43]
The Centers
for Disease Control and Prevention
(CDC) has termed the change an epidemic.[44]
The National
Diabetes Information Clearinghouse
estimates diabetes costs $132 billion in the United States alone every
year. About 5%–10% of diabetes cases in North America are type 1, with the
rest being type 2. The fraction of type 1 in other parts of the world
differs. Most of this difference is not currently understood. The American
Diabetes Association (ADA) cites the 2003 assessment of
the National Center for Chronic Disease Prevention and Health Promotion
(Centers for Disease Control and Prevention) that one in three Americans born
after 2000 will develop diabetes in their lifetimes.[45][46]
According to the ADA, about 18.3%
(8.6 million) of Americans age 60 and older have diabetes.[47]
Diabetes mellitus prevalence increases with age, and the numbers of older
persons with diabetes are expected to grow as the elderly population increases
in number. The National Health and Nutrition Examination Survey (NHANES III)
demonstrated, in the population over 65 years old, 18% to 20% have diabetes,
with 40% having either diabetes or its precursor form of impaired
glucose tolerance.[48]
History
Diabetes was one of the first
diseases described,[49]
with an Egyptian manuscript from c. 1500 BCE
mentioning "too great emptying of the urine".[50]
The first described cases are believed to be of type 1 diabetes.[50]
Indian physicians around the same time identified the disease and classified it
as madhumeha or "honey urine", noting the urine would attract
ants.[50]
The term "diabetes" or "to pass through" was first used in
230 BCE by the Greek Appollonius of Memphis.[50]
The disease was considered as rare during the time of the Roman empire,
with Galen
commenting he had only seen two cases during his career.[50]
This is possibly due the diet and life-style of the ancient people, 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 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 of diabetes with other diseases and he discussed
differential diagnosis from the snakebite which also provokes excessive thirst.
His work remained unknown in the West until the middle of the 16th century
when, in 1552, the first Latin edition was published in Venice.[51]
Type 1 and type 2 diabetes
where identified as separate conditions for the first time by the Indian
physicians Sushruta and Charaka in 400-500 CE with type 1 associated
with youth and type 2 with being overweight.[50]
The term "mellitus" or "from honey" was added by the Briton
John Rolle in the late 1700s to separate the condition from diabetes insipidus, which is also associated with frequent urination.[50]
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.[50]
This was followed by the development of the long-acting insulin NPH in the
1940s.[50]
Etymology
The word diabetes (pron.: /ˌdaɪ.əˈbiːtiːz/ or /ˌdaɪ.əˈbiːtɨs/) comes from Latin diabētēs, which in turn comes from Ancient Greek
διαβήτης (diabētēs) which literally means "a passer through; a siphon."[52]
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.[53][54]
Ultimately, the word comes from Greek διαβαίνειν (diabainein), meaning
"to pass through,"[52]
which is composed of δια- (dia-), meaning "through" and
βαίνειν (bainein), meaning "to go".[53]
The word "diabetes" is first recorded in English, in the form diabete,
in a medical text written around 1425.
The word mellitus
(/mɨˈlaɪtəs/ or /ˈmɛlɨtəs/) comes from the classical Latin
word mellītus, meaning "mellite"[55]
(i.e. sweetened with honey;[55]
honey-sweet[56]).
The Latin word comes from mell-, which comes from mel, meaning
"honey";[55][56]
sweetness;[56]
pleasant thing,[56]
and the suffix -ītus,[55]
whose meaning is the same as that of the English suffix "-ite".[57]
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 diabetic had a sweet taste (glycosuria).[54]
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"[58][59]
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.[60]
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.[61]
In
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 also 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.[62]
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 recognised 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.[62]
The entire wiki article, with images and references, can be
found at:
http://en.wikipedia.org/wiki/Diabetes_mellitus
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