From Wikipedia, the free encyclopedia
| Diabetes mellitus | |
|---|---|
Universal blue circle symbol for diabetes.[1]
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| Classification and external resources | |
| ICD-10 | E10–E14 |
| ICD-9 | 250 |
| MedlinePlus | 001214 |
| eMedicine | med/546 emerg/134 |
| NCI | Diabetes mellitus |
| Patient UK | Diabetes mellitus |
| MeSH | C18.452.394.750 |
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.[2] Symptoms of high blood sugar include frequent urination, increased thirst, and increased hunger. If left untreated, diabetes can cause many complications.[3] Acute complications include diabetic ketoacidosis and nonketotic hyperosmolar coma.[4] Serious long-term complications include cardiovascular disease, stroke, kidney failure, foot ulcers and damage to the eyes.[3]
Diabetes is due to either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin produced.[5] There are three main types of diabetes mellitus:
- Type 1 DM results from the body's failure to produce enough insulin. This form was previously referred to as "insulin-dependent diabetes mellitus" (IDDM) or "juvenile diabetes". The cause is unknown.[3]
- Type 2 DM begins with insulin resistance, a condition in which cells fail to respond to insulin properly.[3] As the disease progresses a lack of insulin may also develop.[6] 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.[3]
- Gestational diabetes, is the third main form and occurs when pregnant women without a previous history of diabetes develop a high blood glucose level.[3]
As of 2014, an estimated 387 million people have diabetes worldwide, [11] with type 2 diabetes making up about 90% of the cases.[12][13] This is equal to 8.3% of the adult population,[13] with equal rates in both women and men.[14] In the years 2012 to 2014, diabetes is estimated to have resulted in 1.5 to 4.9 million deaths per year.[7][11] Diabetes at least doubles the risk of death.[3] The number of people with diabetes is expected to rise to 592 million by 2035.[11] The global economic cost of diabetes in 2014 was estimated to be $612 billion USD.[15] In the United States, diabetes cost $245 billion in 2012.[16]
Signs and symptoms
The classic symptoms of untreated diabetes are weight loss, polyuria (frequent urination), polydipsia (increased thirst), and polyphagia (increased hunger).[17] 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
People (usually with type 1 diabetes) may also experience episodes of diabetic ketoacidosis, a type of metabolic problems 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.[18]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.[18]
Complications
All forms of diabetes increase the risk of long-term complications. These typically develop after many years (10–20), but may be the first symptom in those who have otherwise not received a diagnosis before that time.The major long-term complications relate to damage to blood vessels. Diabetes doubles the risk of cardiovascular disease[19] and about 75% of deaths in diabetics are due to coronary artery disease.[20] Other "macrovascular" diseases are stroke, and peripheral vascular disease.
The primary microvascular complications of diabetes include damage to the eyes, kidneys, and nerves.[21] 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.[21] 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.[21] Damage to the nerves of the body, known as diabetic neuropathy, is the most common complication of diabetes.[21] 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.[22]
Causes
| Feature | Type 1 diabetes | Type 2 diabetes |
|---|---|---|
| Onset | Sudden | Gradual |
| Age at onset | Mostly in children | Mostly in adults |
| Body size | Thin or normal[23] | 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% |
Type 1
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.[24] 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.[25] Still, type 1 diabetes can be accompanied by irregular and unpredictable hyperglycemia, frequently with ketosis, and sometimes with serious hypoglycemia. Other complications include an impaired counterregulatory response to hypoglycemia, infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addison's disease).[25] These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type 1 diabetes.[26]
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
Type 2 diabetes mellitus is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion.[5] 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.[27] 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.[12] 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.[5] Those who are not obese often have a high waist–hip ratio.[5]
Dietary factors also influence the risk of developing type 2 diabetes. Consumption of sugar-sweetened drinks in excess is associated with an increased risk.[28][29] 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.[27] Eating lots of white rice appears to also play a role in increasing risk.[30] A lack of exercise is believed to cause 7% of cases.[31]
Gestational diabetes
Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2–10% of all pregnancies and may improve or disappear after delivery.[32] However, after pregnancy approximately 5–10% of women with gestational diabetes are found to have diabetes mellitus, most commonly type 2.[32] 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. Hyperbilirubinemia may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Labor induction may be indicated with decreased placental function. A Caesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.
Other types
Prediabetes indicates a condition that occurs when a person's blood glucose levels are higher than normal but not high enough for a diagnosis of type 2 DM. Many people destined to develop type 2 DM spend many years in a state of prediabetes.Latent autoimmune diabetes of adults (LADA) is a condition in which type 1 DM develops in adults. Adults with LADA are frequently initially misdiagnosed as having type 2 DM, based on age rather than etiology.
Some cases of diabetes are caused by the body's tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type 2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells. The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (MRDM or MMDM, ICD-10 code E12), was deprecated by the World Health Organization when the current taxonomy was introduced in 1999.[33]
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.
The following is a comprehensive list of other causes of diabetes:[34]
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Pathophysiology
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.[36]
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.[37] 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.[37]
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.[38]
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.[37]
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).[39] 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).[37]
Diagnosis
| Condition | 2 hour glucose | Fasting glucose | HbA1c | |
|---|---|---|---|---|
| Unit | mmol/l(mg/dl) | mmol/l(mg/dl) | mmol/mol | DCCT % |
| Normal | <7 .8="" p=""> | <6 .1="" p=""> | <42 p=""> | <6 .0="" p=""> |
| Impaired fasting glycaemia | <7 .8="" p=""> | ≥ 6.1(≥110) & <7 .0="" p=""> | 42-46 | 6.0–6.4 |
| Impaired glucose tolerance | ≥7.8 (≥140) | <7 .0="" p=""> | 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 hyperglycemia, and is diagnosed by demonstrating any one of the following:[33]
- 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 hyperglycemia and casual plasma glucose ≥ 11.1 mmol/l (200 mg/dl)
- Glycated hemoglobin (HbA1C) ≥ 48 mmol/mol (≥ 6.5 DCCT %).[42]
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.[44] 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.[45] 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).[46]
Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.[47]
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.
Prevention
There is no known preventive measure for type 1 diabetes.[3] Type 2 diabetes can often be prevented by a person being a normal body weight, physical exercise, and following a healthy diet.[3] 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.[48] Limiting sugary beverages and eating less red meat and other sources of saturated fat can also help in the prevention of diabetes.[48] Active smoking is also associated with an increased risk of diabetes, so smoking cessation can be an important preventive measure as well.[49]Management
Diabetes mellitus is a chronic disease, for which there is no known cure except in very specific situations. Management concentrates on keeping blood sugar levels as close to normal ("euglycemia") as possible, without causing hypoglycemia. This can usually be accomplished with diet, exercise, and use of appropriate medications (insulin in the case of type 1 diabetes; oral medications, as well as possibly insulin, in type 2 diabetes).Learning about the disease and actively participating in the treatment is vital for people with diabetes, since the complications of diabetes are far less common and less severe in people who have well-managed blood sugar levels.[50][51] The goal of treatment is an HbA1C level of 6.5%, but should not be lower than that, and may be set higher.[52] Attention is also paid to other health problems that may accelerate the deleterious effects of diabetes. These include smoking, elevated cholesterol levels, obesity, high blood pressure, and lack of regular exercise.[52] Specialised footwear is widely used to reduce the risk of ulceration, or re-ulceration, in at-risk diabetic feet. Evidence for the efficacy of this remains equivocal, however.[53]
Lifestyle
People with diabetes can benefit from education about the disease and treatment, good nutrition to achieve a normal body weight, and sensible exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.[54]Medications
Metformin is generally recommended as a first line treatment for type 2 diabetes, as there is good evidence that it decreases mortality.[55] Routine use of aspirin, however, has not been found to improve outcomes in uncomplicated diabetes.[56] Angiotensin converting enzyme inhibitors (ACEIs) improve outcomes in those with DM while the similar medications angiotensin receptor blockers (ARBs) do not.[57]Type 1 diabetes is typically treated with a combinations of regular and NPH insulin, or synthetic insulin analogs. When insulin is used in type 2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications.[55] Doses of insulin are then increased to effect.[55]
In those with diabetes some recommend blood pressure levels below 120/80 mmHg;[58][59] however, evidence only supports less than or equal to somewhere between 140/90 mmHg to 160/100 mmHg.[60][61]
Pancreatic transplantation
A pancreas transplant is occasionally considered for people with type 1 diabetes who have severe complications of their disease, including end stage renal disease requiring kidney transplantation.[62]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.[63]Epidemiology
Disability-adjusted life year for diabetes mellitus per 100,000 inhabitants in 2004
No data
<100 p="">
100–200
200–300
300–400
400–500
500–600
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600–700
700–800
800–900
900–1,000
1,000–1,500
>1,500
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As at 2013, 382 million people have diabetes worldwide.[13] Type 2 makes up about 90% of the cases.[12][14] This is equal to 8.3% of the adult population[13] with equal rates in both women and men.[14]
In 2014, the International Diabetes Federation (IDF) estimated that diabetes resulted in 4.9 million deaths.[11] The World Health Organization (WHO) estimated that diabetes resulted in 1.5 million deaths in 2012, making it the 8th leading cause of death.[7] 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.[15] More than 80% of diabetic deaths occur in low and middle-income countries.[64]
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.[65] 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.[65]
History
Diabetes was one of the first diseases described,[66] with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine".[67] The first described cases are believed to be of type 1 diabetes.[67] Indian physicians around the same time identified the disease and classified it as madhumeha or "honey urine", noting the urine would attract ants.[67] The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Appollonius of Memphis.[67] The disease was considered rare during the time of the Roman empire, with Galen commenting he had only seen two cases during his career.[67] This is possibly due the diet and life-style of the ancient people, or because the clinical symptoms were observed during the advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea urinosa). The earliest surviving work with a detailed reference to diabetes is that of Aretaeus of Cappadocia (2nd or early 3rd century CE). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness, reflecting the beliefs of the "Pneumatic School". He hypothesized a correlation of diabetes with other diseases and he discussed differential diagnosis from the snakebite which also provokes excessive thirst. His work remained unknown in the West until the middle of the 16th century when, in 1552, the first Latin edition was published in Venice.[68]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.[67] 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.[67] 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.[67] This was followed by the development of the long-acting insulin NPH in the 1940s.[67]
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."[69]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.[70][71][72] Ultimately, the word comes from Greek διαβαίνειν (diabainein), meaning "to pass through,"[69] which is composed of δια- (dia-), meaning "through" and βαίνειν (bainein), meaning "to go".[70] 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"[73] (i.e. sweetened with honey;[73] honey-sweet[74]). The Latin word comes from mell-, which comes from mel, meaning "honey";[73][74] sweetness;[74] pleasant thing,[74] and the suffix -ītus,[73] whose meaning is the same as that of the English suffix "-ite".[75] 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).[71] This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and Persians.
Society and culture
The 1989 "St. Vincent Declaration"[76][77] 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.[78]
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.[79]
In 2010, diabetes-related emergency department (ED) 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 ED visits were for the uninsured.[80]
Naming
The term "type 1 diabetes" has replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes mellitus (IDDM). Likewise, the term "type 2 diabetes" has replaced several former terms, including adult-onset diabetes, obesity-related diabetes, and noninsulin-dependent diabetes mellitus (NIDDM). Beyond these two types, there is no agreed-upon standard nomenclature.Other animals
In animals, diabetes is most commonly encountered in dogs and cats. Middle-aged animals are most commonly affected. Female dogs are twice as likely to be affected as males, while according to some sources, male cats are also more prone than females. In both species, all breeds may be affected, but some small dog breeds are particularly likely to develop diabetes, such as Miniature Poodles.[81] The symptoms may relate to fluid loss and polyuria, but the course may also be insidious. Diabetic animals are more prone to infections. The long-term complications recognised in humans are much rarer in animals. The principles of treatment (weight loss, oral antidiabetics, subcutaneous insulin) and management of emergencies (e.g. ketoacidosis) are similar to those in humans.[81]Research
Inhalable insulin has been developed.[82] The original products were withdrawn due to side effects.[82] Afrezza, under development by pharmaceuticals company MannKind Corporation, was approved by the FDA for general sale in June, 2014 [83]There are several advantages of inhaled insulin: they are convenient and easy to use and provide a useful alternative therapy for patients who cannot use intravenous insulin.[84]
