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Diabetes mellitus

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

   CAPTION: Diabetes mellitus
   Classifications and external resources

     ICD- 10   E 10. —

               E 14.
     ICD- 9    250
   MedlinePlus 001214
    eMedicine  med/546  emerg/134
   MeSH        C18.452.394.750

   Diabetes mellitus is a metabolic disorder, specifically affecting
   carbohydrate metabolism. It is a disease characterized by persistent
   hyperglycemia (high glucose blood sugar). It is a metabolic disease
   that requires medical diagnosis, treatment and lifestyle changes. The
   World Health Organization recognizes three main forms of diabetes: type
   1, type 2 and gestational diabetes (or type 3, occurring during
   pregnancy), although these three "types" of diabetes are more
   accurately considered patterns of pancreatic failure rather than single
   diseases. Type 1 is generally due to autoimmune destruction of the
   insulin-producing cells, while type 2 and gestational diabetes are due
   to insulin resistance by tissues. Type 2 may progress to destruction of
   the insulin-producing cells of the pancreas, but is still considered
   Type 2, even though insulin administration may be required.

   Since the first therapeutic use of insulin (1921) diabetes has been a
   treatable but chronic condition, and the main risks to health are its
   characteristic long-term complications. These include cardiovascular
   disease (doubled risk), chronic renal failure (it is the main cause for
   dialysis in developed world adults), retinal damage which can lead to
   blindness and is the most significant cause of adult blindness in the
   non-elderly in the developed world, nerve damage, erectile dysfunction
   (impotence) and gangrene with risk of amputation of toes, feet, and
   even legs.

                                                         Diabetes mellitus
     __________________________________________________________________

                                                        Types of Diabetes
                                               Diabetes mellitus type 1
                                               Diabetes mellitus type 2
                                                   Gestational diabetes

                                                          Pre-diabetes:
                                               Impaired fasting glycaemia
                                               Impaired glucose tolerance
                                                       Disease Management
                                                   Diabetes management:
                                                      • Diabetic diet
                                                • Anti-diabetic drugs
                                         • Conventional insulinotherapy
                                              • Intensive insulinotherapy
                                                           Other Concerns
                                                 Cardiovascular disease

                                                        Diabetic comas:
                                              • Diabetic hypoglycemia
                                              • Diabetic ketoacidosis
                                              • Nonketotic hyperosmolar

                                                   Diabetic myonecrosis
                                                   Diabetic nephropathy
                                                    Diabetic neuropathy
                                                   Diabetic retinopathy

                                                 Diabetes and pregnancy
                                                              Blood tests
                                                           Fructosamine
                                                   Glucose tolerance test
                                                  Glycosylated hemoglobin

Terminology

   The term diabetes ( Greek: διαβήτης) was coined by Aretaeus of
   Cappadocia. It is derived from the Greek word διαβαίνειν, diabaínein
   that literally means "passing through," or "siphon," a reference to one
   of diabetes' major symptoms—excessive urine production. In 1675 Thomas
   Willis added mellitus from the Latin word for honey (mel in the sense
   of "honey sweet") when he noted that the blood and urine of a diabetic
   has a sweet taste. This had been noticed long before in ancient times
   by the Greeks, Chinese, Egyptians, and Indians. In 1776 Matthew Dobson
   confirmed the sweet taste was because of an excess of a kind of sugar
   in the urine and blood of people with diabetes.

   The ancient Indians tested for diabetes by observing whether ants were
   attracted to a person's urine, and called the ailment "sweet urine
   disease" (Madhumehalai); medieval European doctors tested for it by
   tasting the urine themselves, a scene which was occasionally depicted
   in Gothic reliefs.

   While the term diabetes without a modifier usually refers to diabetes
   mellitus, there is another, rarer condition named diabetes insipidus
   (unquenchable diabetes) in which the urine is not sweet; it can be
   caused by either kidney (nephrogenic DI) or pituitary gland (central
   DI) damage.

History

   Although diabetes has been recognized since antiquity, and treatments
   of various efficacy have been known in various regions since the Middle
   Ages, and in legend for much longer, the elucidation of the
   pathogenesis of diabetes occurred mainly in the 20th century. The
   discovery of the role of the pancreas in diabetes is generally ascribed
   to Joseph von Mering and Oskar Minkowski, European researchers who in
   1889 found that when they completely removed the pancreas of dogs, the
   dogs developed all the signs and symptoms of diabetes and died shortly
   afterward. In 1910, Sir Edward Albert Sharpey-Schafer of Edinburgh
   suggested that people with diabetes were deficient in a single chemical
   that was normally produced by the pancreas—he proposed calling this
   substance insulin. The term is derived from the Latin insula, meaning
   island, in reference to the islets of Langerhans in the pancreas that
   produce insulin.

   The endocrine role of the pancreas in metabolism, and indeed the
   existence of insulin, was not fully clarified until 1921, when Sir
   Frederick Grant Banting and Charles Herbert Best repeated the work of
   Von Mering and Minkowski, but went further and demonstrated that they
   could reverse induced diabetes in dogs by giving them an extract from
   the pancreatic islets of Langerhans of healthy dogs. Banting, Best, and
   colleagues (particularly the chemist Collip) went on to isolate the
   hormone insulin from bovine pancreases at the University of Toronto in
   Canada. This led to the availability of an effective treatment—insulin
   injections—and the first clinical patient was treated in 1922. For
   this, Banting and MacLeod received the Nobel Prize in Physiology or
   Medicine in 1923; both shared their Prize money with others in the team
   who were not recognized, in particular Best and Collip. Banting and
   Best made the patent available without charge and did not attempt to
   control commercial production. Insulin production and therapy rapidly
   spread around the world, largely as a result of this decision.

   Despite the availability of treatment, diabetes remained a major cause
   of death. For instance, statistics reveal that the cause-specific
   mortality rate during 1927 amounted to about 47.7 per 100,000
   population in Malta.

   The distinction between what is now known as type 1 diabetes and type 2
   diabetes was first clearly made by Sir Harold Percival (Harry)
   Himsworth in 1935 and was published in January 1936.

   Other landmark discoveries include:
     * identification of the first of the sulfonylureas in 1942
     * the radioimmunoassay for insulin, as discovered by Rosalyn Yalow
       and Solomon Berson (gaining Yalow the 1977 Nobel Prize in
       Physiology or Medicine)
     * Dr Gerald Reaven's identification of the constellation of symptoms
       now called metabolic syndrome in 1988
     * Demonstration that intensive glycemic control in type 1 diabetes
       reduces chronic side effects more as glucose levels approach
       'normal' in a large longitudinal study, and also in type 2
       diabetics in other large studies
     * identification of the first thiazolidinedione as an effective
       insulin sensitizer during the 1990's
     * Self monitoring of glucose in the home via a finger-stick blood
       sample and a battery powered meter in the 1970's.

Causes & types

Glucose metabolism

   Mechanism of insulin release in normal pancreatic beta cells. Insulin
   production is more or less constant within the beta cells, irrespective
   of blood glucose levels. It is stored within vacuoles pending release,
   via exocytosis, which is triggered by lowered blood glucose levels.
   Enlarge
   Mechanism of insulin release in normal pancreatic beta cells. Insulin
   production is more or less constant within the beta cells, irrespective
   of blood glucose levels. It is stored within vacuoles pending release,
   via exocytosis, which is triggered by lowered blood glucose levels.

   Since insulin is the principal hormone that regulates uptake of glucose
   into most cells from the blood (primarily muscle and fat cells, but not
   central nervous system cells), deficiency of insulin or the
   insensitivity of its receptors plays a central role in all forms of
   diabetes mellitus.

   Much of the carbohydrate in food is converted within a few hours to the
   monosaccharide glucose, the principal carbohydrate in blood. Some
   carbohydrates are not; fruit sugar ( fructose) is usable as cellular
   fuel but is not converted to glucose and does not participate in the
   insulin / glucose metabolic regulatory mechanism, nor does the
   carbohydrate cellulose (though it is actually many glucoses in long
   chains) as humans and many animals have no digestive pathway capable of
   handling it. Insulin is released into the blood by beta cells (β-cells)
   in the pancreas in response to rising levels of blood glucose (e.g.,
   after a meal). Insulin enables most body cells (about 2/3 is the usual
   estimate, including muscle cells and adipose tissue) 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 (the basic sugar used for fuel) to glycogen
   for internal storage in liver and muscle cells. Reduced insulin levels
   result both in the reduced release of insulin from the beta cells and
   in the reverse conversion of glycogen to glucose when glucose levels
   fall, although only glucose thus recovered by the liver re-enters the
   bloodstream as muscle cells lack the necessary export mechanism.

   Higher insulin levels increase many anabolic ("building up") processes
   such as cell growth and duplication, protein synthesis, and fat
   storage. Insulin 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, it is the trigger for
   entering or leaving ketosis (ie, 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, glucose will not be handled
   properly by body cells (about ⅔ require it) or 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.

Type 1 diabetes mellitus

   Type 1 diabetes mellitus - formerly known as insulin-dependent diabetes
   (IDDM), childhood diabetes, or juvenile-onset diabetes - is
   characterized by loss of the insulin-producing beta cells of the islets
   of Langerhans of the pancreas leading to a deficiency of insulin. It
   should be noted that there is no known preventative measure which can
   be taken to avoid type 1 diabetes. Most people affected by type 1
   diabetes are otherwise healthy and of a healthy weight when onset
   occurs. Diet and exercise cannot reverse or prevent type 1 diabetes.
   Sensitivity and responsiveness to insulin are usually normal,
   especially in the early stages. This type comprises up to 10% of total
   cases in North America and Europe, though this varies by geographical
   location. This type of diabetes can affect children or adults, but has
   traditionally been termed "juvenile diabetes" because it represents a
   majority of cases of diabetes affecting children. The most common cause
   of beta cell loss leading to type 1 diabetes is autoimmune destruction,
   accompanied by antibodies directed against insulin and islet cell
   proteins. The principal treatment of type 1 diabetes, even from the
   earliest stages, is replacement of insulin. Without insulin, ketosis
   and diabetic ketoacidosis can develop and coma or death will result.

   Currently, type 1 diabetes can be treated only with insulin, with
   careful monitoring of blood glucose levels using blood testing
   monitors. Emphasis is also placed on lifestyle adjustments (diet and
   exercise). Apart from the common subcutaneous injections, it is also
   possible to deliver insulin via a pump, which allows infusion of
   insulin 24 hours a day at preset levels, and the ability to program a
   push dose (a bolus) of insulin as needed at meal times. This is at the
   expense of an indwelling subcutaneous catheter. It is also possible to
   deliver insulin via an inhaled powder.

   Type 1 treatment must be continued indefinitely at present. Treatment
   does not impair normal activities, if sufficient awareness, appropriate
   care, and discipline in testing and medication. The average glucose
   level for the type 1 patient should be as close to normal (80–120
   mg/dl, 4–6 mmol/l) as possible. Some physicians suggest up to 140–150
   mg/dl (7-7.5 mmol/l) for those having trouble with lower values, such
   as frequent hypoglycemic events. Values above 200 mg/dl (10 mmol/l) are
   often accompanied by discomfort and frequent urination leading to
   dehydration. Values above 300 mg/dl (15 mmol/l) usually require
   immediate treatment and may lead to ketoacidosis. Low levels of blood
   glucose, called hypoglycemia, may lead to seizures or episodes of
   unconsciousness.

Type 2 diabetes mellitus

   Type 2 diabetes mellitus - previously known as adult-onset diabetes,
   maturity-onset diabetes, or non-insulin dependent diabetes mellitus
   (NIDDM) - is due to a combination of defective insulin secretion and
   defective responsiveness to insulin (often termed insulin resistance or
   reduced insulin sensitivity), almost certainly involving the insulin
   receptor in cell membranes. In early stages, the predominant
   abnormality is reduced insulin sensitivity, characterized by elevated
   levels of insulin in the blood. In the early stages, hyperglycemia can
   be reversed by a variety of measures and medications that improve
   insulin sensitivity or reduce glucose production by the liver, but as
   the disease progresses the impairment of insulin secretion worsens, and
   therapeutic replacement of insulin often becomes necessary. There are
   numerous theories as to the exact cause and mechanism for this
   resistance, but central obesity (fat concentrated around the waist in
   relation to abdominal organs, not it seems, subcutaneous fat) is known
   to predispose for insulin resistance, possibly due to its secretion of
   adipokines (a group of hormones) that impair glucose tolerance.
   Abdominal fat is especially active hormonally. Obesity is found in
   approximately 90% of developed world patients diagnosed with type 2
   diabetes. Other factors may include aging and family history, although
   in the last decade it has increasingly begun to affect children and
   adolescents.

   Type 2 diabetes may go unnoticed for years in a patient before
   diagnosis, since the symptoms are typically milder (e.g. lack of
   ketoacidotic episodes) and can be sporadic. However, severe
   complications can result from unnoticed type 2 diabetes, including
   renal failure, vascular disease (including coronary artery disease),
   vision damage, etc.

   Type 2 diabetes is usually first treated by changes in physical
   activity (usually increase), diet (generally decrease carbohydrate
   intake, especially glucose generating carbohydrates), and through
   weight loss. These can restore insulin sensitivity, even when the
   weight loss is modest, for example, around 5 kg (10 to 15 lb), most
   especially when it is in abdominal fat deposits. The next step, if
   necessary, is treatment with oral antidiabetic drugs. As insulin
   production is initially unimpaired, oral medication (often used in
   combination) can still be used that improves insulin production (eg,
   sulfonylureas) and regulate inappropriate release of glucose by the
   liver (and attenuate insulin resistance to some extent (eg, metformin),
   and substantially attenuate insulin resistance (eg,
   thiazolidinediones). If these fail, insulin therapy will be necessary
   to maintain normal or near normal glucose levels. A disciplined regimen
   of blood glucose checks is recommended in most cases, most particularly
   and necessarily when taking most of these medications.

Gestational diabetes

   Gestational diabetes, Type 3, also involves a combination of inadequate
   insulin secretion and responsiveness, resembling type 2 diabetes in
   several respects. It develops during pregnancy and may improve or
   disappear after delivery. Even though it may be transient, gestational
   diabetes may damage the health of the fetus or mother, and about
   20%–50% of women with gestational diabetes develop type 2 diabetes
   later in life.

   Gestational diabetes mellitus occurs in about 2%–5% of all pregnancies.
   It is temporary, and fully treatable, but, if untreated, may cause
   problems with the pregnancy, including macrosomia (high birth weight)
   of the child. It requires careful medical supervision during the
   pregnancy.

Other types

   There are several rare causes of diabetes mellitus that do not fit into
   type 1, type 2, or gestational diabetes:
     * Genetic defects in beta cells (autosomal or mitochondrial)
     * Genetically-related insulin resistance, with or without
       lipodystrophy (abnormal body fat deposition)
     * Diseases of the pancreas (e.g. chronic pancreatitis, cystic
       fibrosis)
     * Hormonal defects
     * Chemicals or drugs

   The tenth version of the International Statistical Classification of
   Diseases (ICD-10) contained a diagnostic entity named
   "malnutrition-related diabetes mellitus" (MRDM or MMDM, ICD-10 code
   E12). A subsequent WHO 1999 working group recommended that MRDM be
   deprecated, and proposed a new taxonomy for alternative forms of
   diabetes. Classifications of non-type 1, non-type 2, non-gestational
   diabetes remains controversial.

Genetics

   Both type 1 and type 2 diabetes are at least partly inherited. Type 1
   diabetes appears to be triggered by some (mainly viral) infections, or
   in a less common group, by stress or environmental factors (such as
   exposure to certain chemicals or drugs). There is a genetic element in
   individual susceptibility to some of these triggers which has been
   traced to particular HLA genotypes (i.e. genetic "self" identifiers
   used by the immune system). However, even in those who have inherited
   the susceptibility, type 1 diabetes mellitus seems to require an
   environmental trigger. A small proportion of people with type 1
   diabetes carry a mutated gene that causes maturity onset diabetes of
   the young (MODY).

   There is a rather stronger inheritance pattern for type 2 diabetes.
   Those with first-degree relatives with type 2 have a much higher risk
   of developing type 2. Concordance among monozygotic twins is close to
   100% , and 25% of those with the disease have a family history of
   diabetes. It is also often connected to obesity, which is found in
   approximately 85% of (North American) patients diagnosed with this
   type, so some experts believe that inheriting a tendency toward obesity
   also contributes.

Diagnosis

Signs and symptoms

   The classical triad of diabetes symptoms is polyuria (frequent
   urination), polydipsia (increased thirst, and consequent increased
   fluid intake) and polyphagia (increased appetite). These symptoms may
   develop quite fast in type 1, particularly in children (weeks or
   months), but may be subtle or completely absent - as well as developing
   much more slowly - in type 2. In type 1 there may also be weight loss
   (despite normal or increased eating), increased appetite, and
   irreducible fatigue. These symptoms may also manifest in type 2
   diabetes in patients whose diabetes is poorly controlled.

   Thirst develops because of osmotic effects—sufficiently high glucose
   (above the " renal threshold") in the blood is excreted by the kidneys,
   but this requires water to carry it and causes increased fluid loss,
   which must be replaced. The lost blood volume will be replaced from
   water held inside body cells, causing dehydration. Prolonged high blood
   glucose causes changes in the shape of the lens in the eye, leading to
   vision changes. Blurred vision is a common complaint leading to a
   diagnosis of type 1; it should always be suspected in such cases.

   Patients (usually with type 1 diabetes) may also present with diabetic
   ketoacidosis (DKA), an extreme state of dysregulation characterized by
   the smell of acetone on the patient's breath, Kussmaul breathing (a
   rapid, deep breathing), polyuria, nausea, vomiting and abdominal pain
   and any of many altered state of consciousness or arousal (eg,
   hostility and mania or, equally, confusion and lethargy). In severe
   DKA, coma (unconsciousness) may follow, progressing to death if
   untreated. In any form, DKA is a medical emergency and requires expert
   attention.

   A rarer but equally severe presentation is hyperosmolar nonketotic
   state, which is more common in type 2 diabetes, and is mainly the
   result of dehydration due to the polyuria. Often, the patient has been
   drinking extreme amounts of sugar-containing drinks, leading to a
   vicious circle in regard to water loss.

Diagnostic approach

   The diagnosis of type 1 diabetes and many cases of type 2 is usually
   prompted by recent-onset symptoms of excessive urination (polyuria) and
   excessive thirst (polydipsia), often accompanied by weight loss. These
   symptoms typically worsen over days to weeks; about 25% of people with
   new type 1 diabetes have developed a degree of diabetic ketoacidosis by
   the time the diabetes is recognized. The diagnosis of other types of
   diabetes is usually made in many other ways. The most common are (1)
   health screening, (2) detection of hyperglycemia when a doctor is
   investigating a complication of longstanding, unrecognized diabetes,
   and (3) new signs and symptoms attributable to the diabetes.
    1. Diabetes screening is recommended for many types of people at
       various stages of life or with several different risk factors. The
       screening test varies according to circumstances and local policy
       and may be a random glucose, a fasting glucose and insulin, a
       glucose two hours after 75 g of glucose, or a formal glucose
       tolerance test. Many healthcare providers recommend universal
       screening for adults at age 40 or 50, and sometimes occasionally
       thereafter. Earlier screening is recommended for those with risk
       factors such as obesity, family history of diabetes, high-risk
       ethnicity (Hispanic/Latin American, American Indian, African
       American, Pacific Island, and South Asian ancestry).
    2. Many medical conditions are associated with a higher risk of
       various types of diabetes and warrant screening. A partial list
       includes: high blood pressure, elevated cholesterol levels,
       coronary artery disease, past gestational diabetes, polycystic
       ovary syndrome, chronic pancreatitis, fatty liver, hemochromatosis,
       cystic fibrosis, several mitochondrial neuropathies and myopathies,
       myotonic dystrophy, Friedreich's ataxia, some of the inherited
       forms of neonatal hyperinsulinism, and many others. Risk of
       diabetes is higher with chronic use of several medications,
       including high-dose glucocorticoids, some chemotherapy agents
       (especially L-asparaginase), and some of the antipsychotics and
       mood stabilizers (especially phenothiazines and some atypical
       antipsychotics).
    3. Diabetes is often detected when a person suffers a problem
       frequently caused by diabetes, such as a heart attack, stroke,
       neuropathy, poor wound healing or a foot ulcer, certain eye
       problems, certain fungal infections, or delivering a baby with
       macrosomia or hypoglycemia.

Diagnostic criteria

   Diabetes mellitus is characterized by recurrent or persistent
   hyperglycemia, and is diagnosed by demonstrating any one of the
   following:
     * fasting plasma glucose level at or above 126 mg/dL or 7.0 mmol/l.
     * plasma glucose at or above 200 mg/dL or 11.1 mmol/l two hours after
       a 75 g oral glucose load in a glucose tolerance test.
     * random plasma glucose at or above 200 mg/dL or 11.1 mmol/l.

   A positive result should be confirmed by any of the above-listed
   methods on a different day, unless there is no doubt as to the presence
   of significantly-elevated glucose levels. Most physicians prefer
   measuring a fasting glucose level because of the ease of measurement
   and time commitment of formal glucose tolerance testing, which can take
   two hours to complete. By definition, two fasting glucose measurements
   above 126 mg/dL or 7.0 mmol/l is considered diagnostic for diabetes
   mellitus.

   Patients with fasting sugars between 6.1 and 7.0 mmol/l (110 and 125
   mg/dL) are considered to have " impaired fasting glucose" and patients
   with plasma glucose at or above 140mg/dL or 7.8 mmol/l two hours after
   a 75 g oral glucose load are considered to have " impaired glucose
   tolerance". "Prediabetes" is either impaired fasting glucose or
   impaired glucose tolerance; the latter in particular is a major risk
   factor for progression to full-blown diabetes mellitus as well as
   cardiovascular disease.

   While not used for diagnosis, an elevated level of glucose bound to
   hemoglobin (termed glycosylated hemoglobin or HbA1c) of 6.0% or higher
   (2003 revised U.S. standard) is considered abnormal by most labs; HbA1c
   is primarily a treatment-tracking test reflecting average blood glucose
   levels over the preceding 90 days (approximately). However, some
   physicians may order this test at the time of diagnosis to track
   changes over time. The current recommended goal for HbA1c in patients
   with diabetes is <7.0%, as defined as "good glycemic control", although
   some guidelines are stricter (<6.5%). People with diabetes that have
   HbA1c levels within this goal have a significantly lower incidence of
   complications from diabetes, including retinopathy and diabetic
   nephropathy.

Complications

   The complications are far less common and less severe in people who
   have well- controlled blood sugar levels. In fact, the better the
   control, the lower the risk of complications. Hence patient education,
   understanding and participation is vital. Healthcare professionals who
   treat diabetes also address other health problems that may accelerate
   the deleterious effects of diabetes. These include smoking ( abstain),
   elevated cholesterol levels (control with diet, exercise or
   medication), obesity (even modest weight loss can be beneficial), high
   blood pressure, and lack of regular exercise.

Acute

   Diabetic ketoacidosis

   Diabetic ketoacidosis (DKA) is an acute, dangerous complication and is
   always a medical emergency. On presentation at hospital, the patient in
   DKA is typically dehydrated and breathing both fast and deeply.
   Abdominal pain is common and may be severe. The level of consciousness
   is normal until late in the process, when lethargy (dulled or reduced
   level of alertness or consciousness) may progress to coma. The
   ketoacidosis can become severe enough to cause hypotension and shock.
   Prompt proper treatment usually results in full recovery, though death
   can result from inadequate treatment, delayed treatment or from a
   variety of complications. It is much more common in type 1 diabetes
   than type 2, but can still occur in patients with type 2 diabetes.

   Nonketotic hyperosmolar coma

   While not always progressing to coma, this hyperosmolar nonketotic
   state (HNS) is another acute problem associated with diabetes mellitus.
   It has many symptoms in common with DKA, but a different cause, and
   requires different treatment. In anyone with very high blood glucose
   levels (usually considered to be above 300 mg/dl or 16 mmol/l), water
   will be osmotically driven out of cells into the blood. The kidneys
   will also be "dumping" glucose into the urine, resulting in concomitant
   loss of water, causing an increase in blood osmolality. If the fluid is
   not replaced (by mouth or intravenously), the osmotic effect of high
   glucose levels combined with the loss of water will eventually result
   in such a high serum osmolality (dehydration). The body's cells may
   become progressively dehydrated as water is drawn out from them and
   excreted. Electrolyte imbalances are also common. This combination of
   changes, especially if prolonged, will result in symptoms of lethargy
   (dulled or reduced level of alertness or consciousness) and may
   progress to coma. As with DKA urgent medical treatment is necessary,
   especially volume replacement. This is the diabetic coma which more
   commonly occurs in type 2 diabetics.

   Hypoglycemia

   Hypoglycemia, or abnormally low blood glucose, is a complication of
   several diabetes treatments. It may develop if the glucose intake does
   not match the treatment. The patient may become agitated, sweaty, and
   have many symptoms of sympathetic activation of the autonomic nervous
   system resulting in feelings similar to dread and immobilized panic.
   Consciousness can be altered, or even lost, in extreme cases, leading
   to coma and/or seizures or even brain damage and death. In patients
   with diabetes this can be caused by several factors, such as too much
   or incorrectly timed insulin, too much exercise or incorrectly timed
   exercise (which decreases insulin requirements) or not enough food or
   insufficient amount of carbohydrates in food. In most cases,
   hypoglycemia is treated with sweet drinks or food. In severe cases, an
   injection of glucagon (a hormone with the opposite effects of insulin)
   or an intravenous infusion of glucose is used for treatment, but
   usually only if the diabetic is unconscious.

   Amputation

   Because diabetics have a very hard time healing even from the most
   modest wound - a papercut, misquito bite, etc - they have a very high
   rate of amputation in the limbs and extremities. A wound will become
   infected, turn gangrenous, and eventually need surgical amputation. For
   this reason perhaps more than any other, the prevention section should
   be read closely.

Chronic

   Microvascular disease

   Chronic elevation of blood glucose level leads to damage of blood
   vessels. In diabetes, the resultant problems are grouped under "
   microvascular disease" (due to damage to small blood vessels) and
   "macrovascular disease" (due to damage to the arteries).

   The damage to small blood vessels leads to a microangiopathy, which
   causes the following organ-related problems:
     * Diabetic retinopathy, growth of friable and poor-quality new blood
       vessels in the retina as well as macular edema (swelling of the
       macula), which can lead to severe vision loss or blindness. Retinal
       damage (from microangiopathy) makes it the most common cause of
       blindness among non-elderly adults in the US.
     * Diabetic neuropathy, abnormal and decreased sensation, usually in a
       stocking distribution starting at the feet but potentially in other
       nerves. When combined with damaged blood vessels this can lead to
       diabetic foot (see below). Other forms of diabetic neuropathy may
       present as mononeuritis or autonomic neuropathy.
     * Diabetic nephropathy, damage to the kidney which can lead to
       chronic renal failure, eventually requiring dialysis. Diabetes
       mellitus is the most common cause of adult kidney failure
       worldwide.

   Macrovascular disease

   Macrovascular disease leads to cardiovascular disease, mainly by
   accelerating atherosclerosis:
     * Coronary artery disease, leading to myocardial infarction ("heart
       attack") or angina
     * Stroke (mainly ischemic type)
     * Peripheral vascular disease, which contributes to intermittent
       claudication (exertion-related foot pain) as well as diabetic foot.
     * Diabetic myonecrosis

   Diabetic foot, often due to a combination of neuropathy and arterial
   disease, may cause skin ulcer and infection and, in serious cases,
   necrosis and gangrene. It is the most common cause of adult amputation,
   usually of toes and or feet, in the US and other Western countries.

   Carotid artery stenosis does not occur more often in diabetes, and
   there appears to be a lower prevalence of abdominal aortic aneurysm.
   However, diabetes does cause higher morbidity, mortality and operative
   risks with these conditions.

Treatment and management

   Diabetes is a chronic disease, and emphasis is on managing short-term
   as well as long-term diabetes-related problems. There is an important
   role for patient education, nutritional support, self glucose
   monitoring, as well as long-term glycemic control. A scrupulous control
   is needed to help reduce the risk of long term complications. In
   addition, given the associated higher risks of cardiovascular disease,
   lifestyle modifications must be implemented to control blood pressure
   and cholesterol by exercising more, smoking cessation, and consuming an
   appropriate diet.

   In countries with a general practitioner system, such as the United
   Kingdom, care may be extended mainly in the community, with
   hospital-based specialist input only in case of complications,
   difficult blood sugar control, or participation in research. In other
   circumstances, general practitioners and specialists may share care of
   a patient in a team approach. Optometrists, podiatrists/chiropodists,
   dietitians, physiotherapists, clinical nurse specialists (eg, Certified
   Diabetic Educators), or nurse practitioners may provide
   multidisciplinary expertise.

   Nowadays, with improved diagnostic support, type-1 (insulin-dependent)
   diabetics can join all kinds of activities. In May 2006 for example,
   the Austrian mountaineer Geri Winkler became the first
   insulin-dependent diabetic to reach the top of Mount Everest.

Curing diabetes

   The fact that type 1 diabetes is due to the failure of one of the cell
   types of a single organ with a relatively simple function (i.e. the
   failure of the islets of Langerhans) has led to the study of several
   possible schemes to cure diabetes. In contrast, type 2 diabetes is more
   complex with fewer prospects of a curative measure, but further
   understanding of the underlying mechanism of insulin resistance may
   make a cure possible. Correcting insulin resistance may provide a cure
   for type 2 diabetes.

   Only those type 1 diabetics who have received a kidney-pancreas
   transplant (when they have developed diabetic nephropathy) and become
   insulin-independent may be considered "cured" from their diabetes.
   Still, they generally remain on long-term immunosuppressive drug and
   there is a possibility the autoimmune phenomenon will develop in the
   transplanted organ.

   Transplants of exogenous beta cells have been performed experimentally
   in both mice and humans, but this measure is not yet practical in
   regular clinical practice. Thus far, like any such transplant, it
   provokes an immune reaction and long-term immunosuppressive drug will
   be needed to protect the transplanted tissue. An alternative technique
   has been proposed to place the transplanted beta cells in a
   semi-permeable container, isolating them from the immune system. Stem
   cell research has also been suggested as a potential avenue for a cure
   since it may permit the regrowth of islet cells which are genetically
   part of the treated individual, thus eliminating the need for
   immuno-suppressants. However, it has also been hypothesised that the
   same mechanism which led to islet destruction originally may simply
   destroy even stem-cell regenerated islets.

   Microscopic or nanotechnological approaches are under investigation as
   well, with implanted stores of insulin metered out by a rapid response
   valve sensitive to blood glucose levels. At least two approaches have
   been proposed and demonstrated in vitro. These are, in some sense,
   closed-loop insulin pumps.

Prevention

   As little is known on the exact mechanism by which type 1 diabetes
   develops, there are no preventive measures available for that form of
   diabetes. Some studies have attributed a protective effect of
   breastfeeding on the development of type 1 diabetes.

   Type 2 diabetes can be prevented in many cases by making changes in
   diet and increasing physical activity. Some studies have shown delayed
   progression to diabetes in predisposed patients through the use of
   metformin or valsartan. Breastfeeding might also be correlated with the
   prevention of type 2 of the disease in mothers.

   As of late 2006, although there are many claims of nutritional cures,
   there is no reliable proof of their effectiveness. In addition, despite
   claims by some that vaccinations may cause diabetes, there are no
   studies proving any such connection.

Public health and policy

   The 1989 Declaration of St Vincent was the result of international
   efforts to improve the care accorded to those with diabetes. Doing so
   is important both in terms of quality of life and life expectancy but
   also economically - expenses 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.

Epidemiology and statistics

   In 2006, according to the World Health Organization, at least 171
   million people worldwide suffer from diabetes. Its incidence is
   increasing rapidly, and it is estimated that by the year 2030, this
   number will double. Diabetes mellitus occurs throughout the world, but
   is more common (especially type 2) in the more developed countries. The
   greatest increase in prevalence is, however, expected to occur in Asia
   and Africa, where most patients will likely be found by 2030. The
   increase in incidence of diabetes in developing countries follows the
   trend of urbanization and lifestyle changes, perhaps most importantly a
   "Western-style" diet. This has suggested an environmental (i.e.,
   dietary) effect, but there is little understanding of the mechanism(s)
   at present, though there is much speculation, some of it most
   compellingly presented.

   Diabetes is in the top 10, and perhaps the top 5, of the most
   significant diseases in the developed world, and is gaining in
   significance there and elsewhere (see big killers).

   For at least 20 years, diabetes rates in North America have been
   increasing substantially. In 2005 there are about 20.8 million people
   with diabetes in the United States alone. According to the American
   Diabetes Association, there are about 6.2 million people undiagnosed
   and about 41 million people that would be considered prediabetic.
   However, the criteria for diagnosing diabetes in the USA means that it
   is more readily diagnosed than in some other countries. The Centers for
   Disease Control has termed the change an epidemic. The National
   Diabetes Information Clearinghouse estimates that 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; this is likely
   due to both differences in the rate of type 1 and differences in the
   rate of other types, most prominently type 2. Most of this difference
   is not currently understood.According to the American Diabetes
   Association, 1 in 3 Americans born after 2000 will develop diabetes in
   their lifetime.

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