DIABETES MELLITUS
Diabetes mellitus (DM), commonly referred to as diabetes, is a group of metabolic diseases in which there are high blood sugar levels over a prolonged period. Symptoms of high blood
sugar include frequent urination, increased thirst, and increased hunger. If left untreated, diabetes can cause many complications. Acute complications include diabetic
ketoacidosis
and nonketotic
hyperosmolar coma.
Serious long-term complications include cardiovascular
disease, stroke, chronic kidney
failure, foot ulcers, and damage to the eyes.
Diabetes is due to either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin
produced. There are three main types of diabetes mellitus:
- Type 1 DM results from the pancreas' failure to produce enough insulin. This form was previously referred to as "insulin-dependent diabetes mellitus" (IDDM) or "juvenile diabetes". The cause is unknown.
- Type 2 DM begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses a lack of insulin may also develop. This form was previously referred to as "non insulin-dependent diabetes mellitus" (NIDDM) or "adult-onset diabetes". The primary cause is excessive body weight and not enough exercise.
- Gestational diabetes, is the third main form and occurs when pregnant women without a previous history of diabetes develop a high blood sugar level.
Prevention and treatment involve a healthy diet, physical exercise, not using tobacco and being a normal body weight. Blood pressure control and proper foot care are also important for people
with the disease. Type 1 diabetes must be managed with insulin injections. Type 2 diabetes may be treated with medications
with or without insulin. Insulin and some oral medications can cause low blood sugar. Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 DM. Gestational diabetes usually resolves after the birth of
the baby.
As of 2014, an estimated 387 million people have diabetes
worldwide, with type 2 diabetes making up about 90% of the cases. This
represents 8.3% of the adult population, with equal rates in both women and
men. From 2012 to 2014, diabetes is estimated to have resulted in 1.5 to 4.9
million deaths each year. Diabetes at least doubles a person's risk of death.
The number of people with diabetes is expected to rise to 592 million by 2035.
The global economic cost of diabetes in 2014 was estimated to be $612 billion USD. In the United States, diabetes
cost $245 billion in 2012. s
Signs and symptoms
Overview of the most significant
symptoms of diabetes
The classic symptoms of untreated diabetes are weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger). 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.
Several other signs and symptoms can mark the onset of
diabetes, although they are not specific to the disease. In addition to the
known ones above, they include blurry 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. A number of skin rashes that can occur in diabetes are collectively
known as diabetic dermadromes.
Diabetic emergencies
Low blood sugar is common in persons with type 1 and type 2 diabetes. 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 issues such as confusion, changes in behavior, seizures, unconsciousness, and (rarely) permanent brain damage or death in severe cases. Mild cases are self-treated by eating or
drinking something high in sugar. Severe cases can lead to unconsciousness and
must be treated with intravenous glucose or injections with glucagon.
People (usually with type 1 diabetes) may also
experience episodes of diabetic
ketoacidosis,
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.
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.
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 and about
75% of deaths in diabetics are due to coronary artery disease. Other "macrovascular"
diseases are stroke, and peripheral vascular
disease.
The primary complications of diabetes due to damage in small
blood vessels include damage to the eyes, kidneys, and nerves. Damage to the
eyes, known as diabetic retinopathy, is caused by damage to the blood
vessels in the retina of the eye, and can result in gradual vision loss and blindness. 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 transplant. Damage to the nerves of the body, known as diabetic neuropathy, is the most common complication of
diabetes 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 wasting 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.
Causes
Diabetes mellitus is classified into four broad categories: type 1, type 2, gestational diabetes, and "other specific
types". The "other specific types" are a collection of a few
dozen individual causes. The term "diabetes", without qualification,
usually refers to diabetes mellitus.
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 a T-cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin. 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. 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
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. Still, type 1 diabetes can be accompanied by
irregular and unpredictable high blood sugar levels, frequently with ketosis, and sometimes with serious low blood sugar levels. Other complications include an
impaired counter regulatory response to low blood sugar, infection, gastroparesis (which leads to erratic absorption of dietary
carbohydrates), and endocrinopathies (e.g., Addison's disease). These phenomena are believed to
occur no more frequently than in 1% to 2% of persons with type 1 diabetes.
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, such as a viral infection or diet.
There is some evidence that suggests an association between type 1 diabetes and
Coxsackie B4 virus. Unlike type 2 diabetes, the onset
of type 1 diabetes is unrelated to lifestyle.
Type 2 diabetes mellitus is characterized by insulin resistance, which may be combined with
relatively reduced insulin secretion. The defective responsiveness of body
tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes
mellitus 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.
Type 2 diabetes is due primarily 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 thirty), lack of physical activity, poor
diet, stress, and urbanization. Excess body fat is associated with
30% of cases in those 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 often have a high waist–hip ratio.
Dietary factors also influence the risk of developing
type 2 diabetes. Consumption of sugar-sweetened drinks in excess is
associated with an increased risk. The type of fats in the diet is also important, with
saturated fats and trans fatty acids increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk. Eating lots of
white rice appears to also play a role in increasing risk. A lack of
exercise is believed to cause 7% of cases.
Comparison
of type 1 and 2 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 2–10% of all pregnancies and may improve or disappear after delivery. However, after
pregnancy approximately 5–10% of women with gestational diabetes are found to
have diabetes mellitus, 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 cardiac and central nervous
system anomalies, and skeletal muscle malformations. Increased fetal insulin
may inhibit fetal surfactant production and cause 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 or an
increased risk of injury associated with macrosomia, such as shoulder dystocia.
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 the uptake of glucose from the blood into most cells of the body, especially
liver, muscle, and adipose tissue. Therefore, deficiency of insulin or the
insensitivity of its receptors plays a central role in all forms
of diabetes mellitus.
The body obtains glucose from three main places: the
intestinal absorption of food, the breakdown of glycogen, 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 balancing 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, if cells
respond poorly to the effects of insulin (insulin
insensitivity
or insulin resistance), or if the insulin itself is
defective, then glucose will not be absorbed properly by the body cells that
require it, and it will not be 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 acidosis.
When the glucose concentration in the blood remains high
over time, the kidneys will reach a threshold of reabsorption, and glucose will be excreted in the urine (glycosuria).[41] 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 (polydipsia).
Diagnosis
Diabetes mellitus is characterized by recurrent or
persistent high blood sugar, and is diagnosed by demonstrating any one of the
following:
- Fasting plasma glucose level ≥ 7.0 mmol/l (126 mg/dl)
- Plasma glucose ≥ 11.1 mmol/l (200 mg/dl) two hours after a 75 g oral glucose load as in a glucose tolerance test
- Symptoms of high blood sugar and casual plasma glucose ≥ 11.1 mmol/l (200 mg/dl)
- Glycated hemoglobin (HbA1C) ≥ 48 mmol/mol (≥ 6.5 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 above 126 mg/dl (7.0 mmol/l) is
considered diagnostic for diabetes mellitus.
Per the World Health
Organization
people with fasting glucose levels from 6.1 to 6.9 mmol/l (110 to
125 mg/dl) are considered to have impaired fasting
glucose. 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 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.
The American Diabetes
Association
since 2003 uses a slightly different range for impaired fasting glucose of 5.6
to 6.9 mmol/l (100 to 125 mg/dl). Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death
from any cause. The rare disease diabetes insipidus has similar symptoms to diabetes
mellitus, but without disturbances in the sugar metabolism (insipidus
means "without taste" in Latin) and does not involve the same disease
mechanisms. Diabetes is a part of the wider condition known as metabolic syndrome.
Prevention
There is no known preventive measure for type 1
diabetes. Type 2 diabetes can often be prevented by a person being a normal body weight, physical exercise, and following a
healthful diet. Dietary changes known to be effective in helping to prevent
diabetes include a diet rich in whole grains and fiber, and choosing good fats, such as polyunsaturated fats found in nuts, vegetable oils, and
fish. Limiting sugary beverages and eating less red meat and other sources of saturated fat can also help in the prevention of diabetes. Active smoking
is also associated with an increased risk of diabetes, so smoking cessation can be an important preventive measure as well.
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, without causing low blood sugar. This can usually be accomplished with
a healthy diet, exercise, weight loss, and use of appropriate medications (insulin
in the case of type 1 diabetes; oral medications, as well as possibly
insulin, in type 2 diabetes).
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
HbA1C level of 6.5%, but should not be lower than that, and may be
set higher. Attention is also paid to other health problems that may accelerate
the negative effects of diabetes. These include smoking, elevated cholesterol levels, obesity, high blood pressure, and lack of regular exercise. Specialized 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.
Lifestyle
People with diabetes can benefit from education about the
disease and treatment, good nutrition to achieve a normal body weight, 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.
Medications used to treat diabetes do so by lowering blood sugar levels. There are a number of different classes of anti-diabetic
medications. Some are available by mouth, such as metformin, while others are only available by injection like insulin. Type 1 diabetes can only be treated with insulin,
typically with a combination of regular and NPH insulin, or synthetic insulin analogs.
Metformin is generally recommended as a first line treatment for
type 2 diabetes, as there is good evidence that it decreases mortality. It
works by decreasing production of glucose by the liver. Several other groups of
drugs, mostly given by mouth, may also decrease blood sugar in type II DM.
These include agents that increase insulin release, agents that decrease
absorption of sugar from the intestines, and agents that make the body more
sensitive to insulin. When insulin is used in type 2 diabetes, a
long-acting formulation is usually added initially, while continuing oral
medications. Doses of insulin are then increased to effect.
Since cardiovascular
disease is a
serious complication associated with diabetes, some recommend blood pressure
levels below 120/80 mmHg; however, evidence only supports less than or
equal to somewhere between 140/90 mmHg to 160/100 mmHg. Amongst medications that lower blood pressure, angiotensin
converting enzyme inhibitors (ACEIs) improve outcomes in those with DM while the similar
medications angiotensin receptor
blockers (ARBs) do
not.[65] Aspirin is also recommended for patient with cardiovascular
problems, however routine use of aspirin has not been found to improve outcomes
in uncomplicated diabetes.
Surgery
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.
Weight loss surgery in those with obesity and type two 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 however is some
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.
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.
Etymology
The word diabetes
(/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." 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. 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 mellitus
(/mɨˈlaɪtəs/ or /ˈmɛlɨtəs/) 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 diabetic had a sweet taste (glycosuria).
This sweet taste had been noticed in urine by the ancient Greeks, Chinese,
Egyptians, Indians, and Persians.
Epidemiology
As of 2013, 382
million people have diabetes worldwide. Type 2 makes up about 90% of the
cases. This is equal to 8.3% of the adult population with equal rates in both
women and men. In 2014, the International Diabetes Federation
(IDF) estimated that diabetes resulted in 4.9 million deaths. The World Health Organization (WHO) estimated
that diabetes resulted in 1.5 million deaths in 2012, making it the 8th leading
cause of death. The discrepancy between the two estimates is due to the fact
that cardiovascular diseases are often the cause of death for individuals with
diabetes; the IDF uses modelling to estimate the amount of deaths that could be
attributed to diabetes. More than 80% of diabetic deaths occur in low and
middle-income countries.
Diabetes
mellitus occurs throughout the world, but is more common (especially type 2) in
more developed countries. The greatest increase in rates was expected to occur
in Asia and Africa, where most people with diabetes will probably live in 2030.
The increase in rates in developing countries follows the trend of urbanization
and lifestyle changes, including a "Western-style" diet. This has
suggested an environmental (i.e., dietary) effect, but there is little
understanding of the mechanism(s) at present.
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