出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/08/11 21:39:17」(JST)
| Diabetes mellitus | |
|---|---|
| Universal blue circle symbol for diabetes.[1] | |
| Pronunciation |
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| Specialty | Endocrinology |
| Symptoms | Frequent urination, increased thirst, increased hunger[2] |
| Complications | Diabetic ketoacidosis, nonketotic hyperosmolar coma, heart disease, stroke, chronic kidney failure, foot ulcers[3][2] |
| Diagnostic method | High blood sugar[2] |
| Treatment | Healthy diet, physical exercise[2] |
| Medication | Insulin, metformin[2][4] |
| Frequency | 415 million (8.5%)[5][2] |
| Deaths | 1.5–5.0 million per year[6][5] |
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[edit on Wikidata]
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Diabetes mellitus (DM), commonly referred to as diabetes, is a group of metabolic disorders in which there are high blood sugar levels over a prolonged period.[7] Symptoms of high blood sugar include frequent urination, increased thirst, and increased hunger. If left untreated, diabetes can cause many complications.[2] Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death.[3] Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, and damage to the eyes.[2]
Diabetes is due to either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin produced.[8] There are three main types of diabetes mellitus:
Prevention and treatment involve maintaining a healthy diet, regular physical exercise, a normal body weight, and avoiding use of tobacco. Control of blood pressure and maintaining proper foot care are important for people with the disease. Type 1 DM must be managed with insulin injections.[2] Type 2 DM may be treated with medications with or without insulin.[6] Insulin and some oral medications can cause low blood sugar.[10] Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 DM.[11] Gestational diabetes usually resolves after the birth of the baby.[12]
As of 2015[update], an estimated 415 million people had diabetes worldwide,[5] with type 2 DM making up about 90% of the cases.[13][14] This represents 8.3% of the adult population,[14] with equal rates in both women and men.[15] As of 2014[update], trends suggested the rate would continue to rise.[16] Diabetes at least doubles a person's risk of early death.[2] From 2012 to 2015, approximately 1.5 to 5.0 million deaths each year resulted from diabetes.[6][5] The global economic cost of diabetes in 2014 was estimated to be US$612 billion.[17] In the United States, diabetes cost $245 billion in 2012.[18]
The classic symptoms of untreated diabetes are weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger).[19] Symptoms may develop rapidly (weeks or months) in type 1 DM, while they usually develop much more slowly and may be subtle or absent in type 2 DM.
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.[20]
Low blood sugar is common in persons with type 1 and type 2 DM. 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 such as aggressiveness, seizures, unconsciousness, and (rarely) permanent brain damage or death in severe cases.[21][22] Moderate hypoglycemia may easily be mistaken for drunkenness;[23] rapid breathing and sweating, cold, pale skin are characteristic of hypoglycemia but not definitive.[24] Mild to moderate 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.[citation needed]
People (usually with type 1 DM) 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.[25]
A rare but equally severe possibility is hyperosmolar hyperglycemic state, which is more common in type 2 DM and is mainly the result of dehydration.[25]
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[26] and about 75% of deaths in diabetics are due to coronary artery disease.[27] Other "macrovascular" diseases are stroke, and peripheral artery disease.
The primary complications of diabetes due to damage in small blood vessels include damage to the eyes, kidneys, and nerves.[28] 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.[28] Damage to the kidneys, known as diabetic nephropathy, can lead to tissue scarring, urine protein loss, and eventually chronic kidney disease, sometimes requiring dialysis or kidney transplantation.[28] Damage to the nerves of the body, known as diabetic neuropathy, is the most common complication of diabetes.[28] The symptoms can include numbness, tingling, pain, and altered pain sensation, which can lead to damage to the skin. Diabetes-related foot problems (such as diabetic foot ulcers) may occur, and can be difficult to treat, occasionally requiring amputation. Additionally, proximal diabetic neuropathy causes painful muscle atrophy and weakness.
There is a link between cognitive deficit and diabetes. Compared to those without diabetes, those with the disease have a 1.2 to 1.5-fold greater rate of decline in cognitive function.[29] Being diabetic, especially when on insulin, increases the risk of falls in older people.[30]
| Feature | Type 1 diabetes | Type 2 diabetes |
|---|---|---|
| Onset | Sudden | Gradual |
| Age at onset | Mostly in children | Mostly in adults |
| Body size | Thin or normal[31] | Often obese |
| Ketoacidosis | Common | Rare |
| Autoantibodies | Usually present | Absent |
| Endogenous insulin | Low or absent | Normal, decreased or increased |
| Concordance in identical twins |
50% | 90% |
| Prevalence | ~10% | ~90% |
Diabetes mellitus is classified into four broad categories: type 1, type 2, gestational diabetes, and "other specific types".[8] The "other specific types" are a collection of a few dozen individual causes.[8] Diabetes is a more variable disease than once thought and people may have combinations of forms.[32] 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 pancreatic islets, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, in which a T cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin.[33] 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.[citation needed]
"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.[34] 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 counterregulatory response to low blood sugar, infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addison's disease).[34] These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type 1 diabetes.[35]
Type 1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. The increase of incidence of type 1 diabetes reflects the modern lifestyle.[36] In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors,[37] such as a viral infection or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans.[37][38] Among dietary factors, data suggest that gliadin (a protein present in gluten) may play a role in the development of type 1 diabetes, but the mechanism is not fully understood.[39][40]
Type 2 DM is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion.[8] 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 DM is the most common type of diabetes mellitus.[citation needed]
In the early stage of type 2, the predominant abnormality is reduced insulin sensitivity. At this stage, high blood sugar can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce the liver's glucose production.
Type 2 DM is primarily due to lifestyle factors and genetics.[41] A number of lifestyle factors are known to be important to the development of type 2 DM, including obesity (defined by a body mass index of greater than 30), lack of physical activity, poor diet, stress, and urbanization.[13] 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.[8] Even those who are not obese often have a high waist–hip ratio.[8]
Dietary factors also influence the risk of developing type 2 DM. Consumption of sugar-sweetened drinks in excess is associated with an increased risk.[42][43] The type of fats in the diet is also important, with saturated fat and trans fats increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk.[41] Eating lots of white rice also may increase the risk of diabetes.[44] A lack of physical activity is believed to cause 7% of cases.[45]
Gestational diabetes mellitus (GDM) resembles type 2 DM 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.[46] However, after pregnancy approximately 5–10% of women with gestational diabetes are found to have diabetes mellitus, most commonly type 2.[46] Gestational diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy. Management may include dietary changes, blood glucose monitoring, and in some cases, insulin may be required.
Though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital heart and central nervous system abnormalities, and skeletal muscle malformations. Increased levels of insulin in a fetus's blood may inhibit fetal surfactant production and cause 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.[citation needed]
Maturity onset diabetes of the young (MODY) is an autosomal dominant inherited form of diabetes, due to one of several single-gene mutations causing defects in insulin production.[47] It is significantly less common than the three main types. The name of this disease refers to early hypotheses as to its nature. Being due to a defective gene, this disease varies in age at presentation and in severity according to the specific gene defect; thus there are at least 13 subtypes of MODY. People with MODY often can control it without using insulin.
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.
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 cause.
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.[48]
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.
"Type 3 diabetes" has been suggested as a term for Alzheimer's disease as the underlying processes may involve insulin resistance by the brain.[49]
The following is a comprehensive list of other causes of diabetes:[50]
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Insulin is the principal hormone that regulates the uptake of glucose from the blood into most cells of the body, especially liver, adipose tissue and muscle, except smooth muscle, in which insulin acts via the IGF-1. Therefore, deficiency of insulin or the insensitivity of its receptors plays a central role in all forms of diabetes mellitus.[52]
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.[53] 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.[53]
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.[54]
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.[53]
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).[55] 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).[53]
| Condition | 2 hour glucose | Fasting glucose | HbA1c | |
|---|---|---|---|---|
| Unit | mmol/l(mg/dl) | mmol/l(mg/dl) | mmol/mol | DCCT % |
| Normal | <7.8 (<140) | <6.1 (<110) | <42 | <6.0 |
| Impaired fasting glycaemia | <7.8 (<140) | ≥6.1(≥110) & <7.0(<126) | 42-46 | 6.0–6.4 |
| Impaired glucose tolerance | ≥7.8 (≥140) | <7.0 (<126) | 42-46 | 6.0–6.4 |
| Diabetes mellitus | ≥11.1 (≥200) | ≥7.0 (≥126) | ≥48 | ≥6.5 |
Diabetes mellitus is characterized by recurrent or persistent high blood sugar, and is diagnosed by demonstrating any one of the following:[48]
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.[59] 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.[60] 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.[61] 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).[62]
Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.[63]
There is no known preventive measure for type 1 diabetes.[2] Type 2 diabetes – which accounts for 85-90% of all cases – can often be prevented or delayed by maintaining a normal body weight, engaging in physical activity, and consuming a healthful diet.[2] Higher levels of physical activity (more than 90 minutes per day) reduce the risk of diabetes by 28%.[64] Dietary changes known to be effective in helping to prevent diabetes include maintaining a diet rich in whole grains and fiber, and choosing good fats, such as the polyunsaturated fats found in nuts, vegetable oils, and fish.[65] Limiting sugary beverages and eating less red meat and other sources of saturated fat can also help prevent diabetes.[65] Tobacco smoking is also associated with an increased risk of diabetes and its complications, so smoking cessation can be an important preventive measure as well.[66]
The relationship between type 2 diabetes and the main modifiable risk factors (excess weight, unhealthy diet, physical inactivity and tobacco use) is similar in all regions of the world. There is growing evidence that the underlying determinants of diabetes are a reflection of the major forces driving social, economic and cultural change: globalization, urbanization, population aging, and the general health policy environment.[67]
Diabetes mellitus is a chronic disease, for which there is no known cure except in very specific situations.[68] 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).[citation needed]
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.[69][70] The goal of treatment is an HbA1C level of 6.5%, but should not be lower than that, and may be set higher.[71] 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.[71] 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.[72]
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.[73]
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 such as GLP-1 agonists. Type 1 diabetes can only be treated with insulin, typically with a combination of regular and NPH insulin, or synthetic insulin analogs.[citation needed]
Metformin is generally recommended as a first line treatment for type 2 diabetes, as there is good evidence that it decreases mortality.[4] It works by decreasing the liver's production of glucose.[74] 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.[74] When insulin is used in type 2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications.[4] Doses of insulin are then increased to effect.[4][75]
Since cardiovascular disease is a serious complication associated with diabetes, some have recommended blood pressure levels below 130/80 mmHg.[76] However, evidence supports less than or equal to somewhere between 140/90 mmHg to 160/100 mmHg; the only additional benefit found for blood pressure targets beneath this range was an isolated decrease in stroke risk, and this was accompanied by an increased risk of other serious adverse events.[77][78] A 2016 review found potential harm to treating lower than 140 mmHg.[79] Among 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.[80] Aspirin is also recommended for people with cardiovascular problems, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes.[81]
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.[82]
Weight loss surgery in those with obesity and type two diabetes is often an effective measure.[83] Many are able to maintain normal blood sugar levels with little or no medications following surgery[84] and long-term mortality is decreased.[85] There is, however, a short-term mortality risk of less than 1% from the surgery.[86] The body mass index cutoffs for when surgery is appropriate are not yet clear.[85] It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.[87]
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.[88]
Rates of diabetes worldwide in 2000 (per 1,000 inhabitants) — world average was 2.8%.
|
no data
≤ 7.5
7.5–15
15–22.5
22.5–30
30–37.5
37.5–45
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45–52.5
52.5–60
60–67.5
67.5–75
75–82.5
≥ 82.5
|
Diabetes mellitus deaths per million persons in 2012
As of 2016, 422 million people have diabetes worldwide,[89] up from an estimated 382 million people in 2013[14] and from 108 million in 1980.[89] Accounting for the shifting age structure of the global population, the prevalence of diabetes is 8.5% among adults, nearly double the rate of 4.7% in 1980.[89] Type 2 makes up about 90% of the cases.[13][15] Some data indicate rates are roughly equal in women and men,[15] but male excess in diabetes has been found in many populations with higher type 2 incidence, possibly due to sex-related differences in insulin sensitivity, consequences of obesity and regional body fat deposition, and other contributing factors such as high blood pressure, tobacco smoking, and alcohol intake.[90][91]
The World Health Organization (WHO) estimates that diabetes mellitus resulted in 1.5 million deaths in 2012, making it the 8th leading cause of death.[6][89] However another 2.2 million deaths worldwide were attributable to high blood glucose and the increased risks of cardiovascular disease and other associated complications (e.g. kidney failure), which often lead to premature death and are often listed as the underlying cause on death certificates rather than diabetes.[89][92] For example, in 2014, the International Diabetes Federation (IDF) estimated that diabetes resulted in 4.9 million deaths worldwide,[16] using modeling to estimate the total number of deaths that could be directly or indirectly attributed to diabetes.[17]
Diabetes mellitus occurs throughout the world but is more common (especially type 2) in more developed countries. The greatest increase in rates has however been seen in low- and middle-income countries,[89] where more than 80% of diabetic deaths occur.[93] The fastest prevalence increase is expected to occur in Asia and Africa, where most people with diabetes will probably live in 2030.[94] The increase in rates in developing countries follows the trend of urbanization and lifestyle changes, including increasingly sedentary lifestyles, less physically demanding work and the global nutrition transition, marked by increased intake of foods that are high energy-dense but nutrient-poor (often high in sugar and saturated fats, sometimes referred to as the "Western-style" diet).[89][94]
Diabetes was one of the first diseases described,[95] with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine".[96] The Ebers papyrus includes a recommendation for a drink to be taken in such cases.[97] The first described cases are believed to be of type 1 diabetes.[96] Indian physicians around the same time identified the disease and classified it as madhumeha or "honey urine", noting the urine would attract ants.[96][97]
The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Apollonius of Memphis.[96] The disease was considered rare during the time of the Roman empire, with Galen commenting he had only seen two cases during his career.[96] This is possibly due to the diet and lifestyle of the ancients, or because the clinical symptoms were observed during the advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea urinosa).[98]
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 1552, when the first Latin edition was published in Venice.[98]
Type 1 and type 2 diabetes were 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.[96] 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.[96] 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.[96] This was followed by the development of the long-acting insulin NPH in the 1940s.[96]
The word diabetes (/ˌdaɪ.əˈbiːtiːz/ or /ˌdaɪ.əˈbiːtᵻs/) comes from Latin diabētēs, which in turn comes from Ancient Greek διαβήτης (diabētēs), which literally means "a passer through; a siphon".[99] 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.[100][101] Ultimately, the word comes from Greek διαβαίνειν (diabainein), meaning "to pass through,"[99] which is composed of δια- (dia-), meaning "through" and βαίνειν (bainein), meaning "to go".[100] The word "diabetes" is first recorded in English, in the form diabete, in a medical text written around 1425.
The word mellitus (/mᵻˈlaɪtəs/ or /ˈmɛlᵻtəs/) comes from the classical Latin word mellītus, meaning "mellite"[102] (i.e. sweetened with honey;[102] honey-sweet[103]). The Latin word comes from mell-, which comes from mel, meaning "honey";[102][103] sweetness;[103] pleasant thing,[103] and the suffix -ītus,[102] whose meaning is the same as that of the English suffix "-ite".[104] 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.
The 1989 "St. Vincent Declaration"[105][106] 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.[107]
People with diabetes who have neuropathic symptoms such as numbness or tingling in feet or hands are twice as likely to be unemployed as those without the symptoms.[108]
In 2010, diabetes-related emergency room (ER) visit rates in the United States were higher among people from the lowest income communities (526 per 10,000 population) than from the highest income communities (236 per 10,000 population). Approximately 9.4% of diabetes-related ER visits were for the uninsured.[109]
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.[citation needed]
Diabetes mellitus is also occasionally known as "sugar diabetes" to differentiate it from diabetes insipidus.[110]
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.[111] The symptoms may relate to fluid loss and polyuria, but the course may also be insidious. Diabetic animals are more prone to infections. The long-term complications recognized in humans are much rarer in animals. The principles of treatment (weight loss, oral antidiabetics, subcutaneous insulin) and management of emergencies (e.g. ketoacidosis) are similar to those in humans.[111]
Inhalable insulin has been developed.[112] The original products were withdrawn due to side effects.[112] Afrezza, under development by the pharmaceuticals company MannKind Corporation, was approved by the FDA for general sale in June 2014.[113] An advantage to inhaled insulin is that it may be more convenient and easy to use.[114]
Transdermal insulin in the form of a cream has been developed and trials are being conducted on people with type 2 diabetes.[115][116]
So far, none of the hypotheses accounting for virus-induced beta cell autoimmunity has been supported by stringent evidence in humans, and the involvement of several mechanisms rather than just one is also plausible.
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Diseases of the endocrine system (E00–E35, 240–259)
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Diabetes (E10–E14, 250)
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| リンク元 | 「血糖降下薬」「100Cases 27」「100Cases 16」「diabetic」 |
| 拡張検索 | 「maturity-onset diabetes of the young」 |
k氏より
インスリンの抽出は大変意図的に行われたのに対し、スルフォニルウレア薬(SU)は偶然に見つかりました。で、1950年代にはじめに二型糖尿病の患者に使われるようになりました。いまでは20種類くらいのSUが広く世界で使われています。 1997にはメグリチニドが臨床適用されました。食後高血糖の治療薬としてはじめて使用された薬です。 メタフォルミンというビグアナイド薬(BG)は、ヨーロッパで広く使われていましたが、1995年にアメリカでも認可されました。 チアゾリジン1997年に市場導入され、二番目にメジャーなインスリン刺激薬として使用されています。この種類の薬には、広汎な肝障害を起こしにくく、世界中で使われています。
膵臓のβ細胞の刺激によって、インスリンを放出させ、血糖値を下げます。 治療が長引くと、インスリン分泌というSUのβ細胞刺激性の効果が薄れてきますが、β細胞上のSU受容体のダウンレギュレーションによるものです。また、SUはソマトスタチンの放出を刺激します。ソマトスタチンはグルカゴン分泌を抑制しているので、これも関係SUの糖を下げる効果と関係しています。 SUはATP感受性Kチャンネルを抑制します。Kレベルが下がると、まく表面における、脱分極を促し、電位依存性カルシウムチャンネルを通じたカルシウムイオンの流入を促進します。 SUには無視できない膵臓外作用があるという議論があります。確かにありうべきことですが、2型糖尿病の患者の治療においては、それほど重要なことではないようです。
SU薬はそれぞれが似たような作用スペクトラムを持っているので、薬物動態的な特性がここの薬を区別する手がかりです。腸管からのSU薬の吸収の割合は薬によって違いますが、食物や、高血糖は、この吸収を抑制します。高血糖はそれ自身、腸管の運動を抑制するので、ほかの薬の吸収も阻害します。血漿濃度が効果的な値にまで達する時間を考えると、半減期の短いSUは、食前三十分に投与するのが適切です。SU薬は90から99パーセントくらい血中たんぱく質と結合し、特にアルブミンと結合します。 第一世代のSUは半減期や分布において、大きく違っています。この半減期や作用時間の不一致の理由はいまだはっきりしていません。 SUはすべて肝臓で代謝を受け、尿中に排泄されます。なので、肝不全、腎不全患者には要注意で処方します。
めったにありませんが、第一世代服用患者では、4パーセントの割合でおきます。第二世代ではもっと少ないでしょう。低血糖による昏睡がしばしば問題になります。腎不全や肝不全がある高齢者の患者でおきやすいです。 重症の低血糖は脳血管障害も起こしうる。急性の神経障害が見つかった高齢患者では血中グルコースレベルを測るのが大事です。半減期の長いSUもあるので、24から48時間のグルコースを輸液します。 第一世代は多くの薬物と相互作用を持っています。 ほかに、吐き気嘔吐、胆汁うっ滞性黄疸、脱顆粒球症、再生不良性・溶血性貧血、全身性のアレルギー症状があります。 SUが心血管障害による死亡率を上げるのかについては議論の余地あり。
SUは、食事療法だけでは十分なコントロールを得られない2型糖尿病患者の血糖コントロールに用いられます。禁忌はtype 1 DM(diabetes mellitus:糖尿病)、妊婦、授乳中の患者、腎障害や肝障害の患者です。 普通の患者なら五割から八割くらい、経口の糖尿病治療薬が効きます。インスリン療法が必要になる患者もいます。 トルブタマイドの一日量は500ミリグラムで、3000ミリグラムが最大の許容量です。SUの治療成績の評価は患者の様子を頻繁に観察しながら、行います。 SUとインスリンの併用療法はtype 1, type 2 両方の糖尿病で用いられていますが、βセルの残存能力がないとうまくいきません。
レパグリニドはメグリチニドクラスの経口インスリン分泌促進物質です。化学構造上、SUとは異なっており、安息香酸から分離されたものです。 SU薬と同様にレパグリニドは膵臓βセルにおけるATP依存性Kチャンネルを閉じることによりインスリン分泌を促進します。AEもSU薬と同様、低血糖です。
Dふぇにるアラニンから分離された薬。レパグリニドよりもSEとして低血糖が認められづらいです。
メトフォルミンとフェノフォルミンは1957年に市場導入され、ブフォルミンが1958年に導入されました。ブフォルミンは使用が制限されていますが、前者二つは広く使われています。フェノフォルミンは1970年代に乳酸アシドーシスのAEによって市場から姿を消しました。メトフォルミンはそのようなAEは少なく、ヨーロッパカナダで広く使われています。アメリカでは1995年に使用可能に。メトフォルミンは単独かSUと併用して使われます。
ものの言い方によると、メトフォルミンは抗高血糖であって、血糖を下げる薬ではありません。膵臓からのインスリン放出は促さないので、どんな大容量でも低血糖は起こしません。グルカゴン・コルチゾール・成長ホルモン・ソマトスタチンにも影響なし。肝での糖新生を抑制したり、筋や脂肪におけるインスリンの働きを増すことで、血糖を押さえます。
小腸から吸収。安定な構造で、血中の蛋白と結合しないで、そのまま尿中に排泄。半減期は二時間。2.5グラムを食事と一緒に飲むのがアメリカで最もお勧めの最大用量。
メトフォルミンは腎不全の患者には投与しないこと。肝障害や、乳酸アシドーシスの既往、薬物治療中の心不全、低酸素性の慢性肺疾患なども合併症として挙げられる。乳酸アシドーシスはしかしながら、めちゃくちゃまれである。1000人年(たとえば100人いたら、10年のうちにという意味の単位。または1000人いたら1年につき、ということ。)につき0.1という割合。 メトフォルミンの急性のAEは患者の20パーセントに見られ、下痢、腹部不快感、吐き気、金属の味、食欲不振などです。メタフォルミンを飲んでいる間はビタミンB12や葉酸のきゅうしゅうが 落ちています。カルシウムをサプリで取ると、ビタミンB12の吸収が改善されます。 血中乳酸濃度が3ミリMに達するとか、腎不全・肝不全の兆候が見られたら、メタフォルミンは中止しましょう。
PPARγに効く。(ペルオキシソーム・プロライファレーター・アクチベイティッド・受容体、つまりペルオキシソーム増殖活性受容体みたいな。)PPARγに結合して、インスリン反応性をまして、炭水化物とか、脂質の代謝を調整します。
ロジグリタゾンとピオグリタゾンは一日一度。チアゾリジンは肝にて代謝され、腎不全のある患者にも投与できますが、活動性の肝疾患があるときや肝臓のトランスアミナーゼが上昇しているときは、使用しないこと。 ロジグリタゾンはCYP2C8で代謝されますがピオグリタゾンはCYP3A4とCYP2C8で代謝されます。ほかの薬との相互作用や、チアゾリジン同士の相互作用はいまだ報告されていませんが、研究中です。
ピオグリタゾンとロジグリタゾンは肝毒性とはめったに関係しませんが、肝機能をモニターする必要があります。心不全のある患者はまずそちらを治療してから。
αGIは小腸の刷子縁におけるαグルコシダーゼの働きを阻害することによって、でんぷん・デキストリン・ダイサッカリダーゼの吸収を抑制します。 インスリンを増やす作用はないので、低血糖もおきません。吸収がよくない薬なので、食事の開始と一緒に飲むとよいです。 アカルボースとミグリトールは食後高血糖の抑制に使われます。 αGIは用量依存性に、消化不良・ガス膨満・下痢などをきたします。αGIとインスリンを併用中に低血糖症状が出たら、、グルコースを補充します。
経口から、グルコースが静脈を通ると、インスリンが上がることがわかっていました。消化管の上部からはGIP、消化管下部からはGLP1というホルモンが出ていて、糖依存性のインスリン放出を促していることがわかりました。これらのホルモンはインクレチンといわれています。この二つのホルモンは別の働き方でインスリンの放出を促進します。GIPはtype 2 DMではインスリン分泌を促進する能力がほとんど失われています。一方でGLP1は糖依存性のインスリン分泌を強く促しています。つまりtype 2 DMの治療ではGIPをターゲットにすればよいということになります。GLPはグルカゴンを抑制し。空腹感を押さえ、食欲を抑えます。体重減少も実現できます。この長所を相殺するように、GLP1は迅速にDPPIV(ヂペプチジルペプチダーゼ4エンザイム)によって負活化されます。つまり、GLP1を治療に使うなら、連続的に体に入れなければなりません。GLP1受容体のアゴニストが研究され、これはDPPIVにたいして抵抗性があります。 そのほかのGLP1療法のアプローチに仕方としては、DPPIVプロテアーゼの不活性化で、それによってGLP1の循環量を増やそうとするものです。type 2 DM治療に新しい薬がでるかもしれないですね。