Old page wikitext, before the edit (old_wikitext ) | '{{two other uses||the disease characterized by excretion of large amounts of very dilute urine|diabetes insipidus|diabetes mellitus in pets|diabetes in cats and dogs}}{{Globalize/USA}}
{{Infobox disease
| Name=Diabetes mellitus
| Image=Blue circle for diabetes.svg
| Caption=Universal blue circle symbol for diabetes.<ref>{{cite web|title=Diabetes Blue Circle Symbol|url=http://www.diabetesbluecircle.org|date=17 March 2006|publisher=International Diabetes Federation}}</ref>
| ICD10={{ICD10|E|10||e|10}}–{{ICD10|E|14||e|10}}
| ICD9={{ICD9|250}}
| MedlinePlus=001214
| EMedicineSubj=med
| EMedicineTopic=546
| EMedicine_mult={{eMedicine2|emerg|134}}
| MeshName=Diabetes
| MeshNumber=C18.452.394.750
}}
'''Diabetes mellitus''' ({{pron-en|ˌdaɪ.əˈbiːtiːz}} or {{IPA|/ˌdaɪ.əˈbiːtɨs/}}; {{IPA|/mɨˈlaɪtəs/}} or {{IPA|/ˈmɛlɨtəs/}})—often referred to simply as '''diabetes'''—is a condition in which the body either does not produce enough, or does not properly respond to, [[insulin]], a [[hormone]] produced in the [[pancreas]]. Insulin enables cells to absorb glucose in order to turn it into energy. In diabetes, the body either fails to properly respond to its own insulin, does not make enough insulin, or both. This causes glucose to accumulate in the blood, often leading to various complications.<ref name="Rother" /><ref name="diag">{{cite book|last=L M Tierney, S J McPhee|first=M A Papadakis|title=Current medical Diagnosis & Treatment. International edition|publisher=Lange Medical Books/McGraw-Hill|year=2002|pages=1203–15|location=New York|isbn=0-07-137688-7 }}</ref>
Many types of diabetes are recognized:<ref name="diag"/> The principal three are:
* ''[[Diabetes mellitus type 1|Type 1]]:'' Results from the body's failure to produce insulin. It is estimated that 5-10% of Americans who are diagnosed with diabetes have type 1 diabetes. Presently almost all persons with type 1 diabetes must take insulin injections.
* ''[[Diabetes mellitus type 2|Type 2]]:'' Results from [[Insulin resistance]], a condition in which cells fail to use insulin properly, sometimes combined with relative insulin deficiency. Most Americans who are diagnosed with diabetes have type 2 diabetes. Many people destined to develop type 2 diabetes spend many years in a state of ''[[Prediabetes|Pre-diabetes]]:'' Termed "America's largest healthcare epidemic,"<ref>Handelsman, Yehuda, MD. "A Doctor's Diagnosis: Prediabetes." ''Power of Prevention,'' Vol 1, Issue 2, 2009.</ref>{{rp|10-11|date=July 2009}}, pre-diabetes 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 diabetes. As of 2009 there are 57 million Americans who have pre-diabetes.<ref name="ADA709">{{cite web | title=All About Diabetes" | publisher=American Diabetes Association | accessdate=2009-07-01 | url=http://www.diabetes.org/about-diabetes.jsp}}</ref>
* ''[[Gestational diabetes]]:'' Pregnant women who have never had diabetes before but who have high blood sugar (glucose) levels during pregnancy are said to have gestational diabetes. Gestational diabetes affects about 4% of all pregnant women. It may precede development of type 2 (or rarely type 1).
*Many other forms of diabetes mellitus are categorized separately from these. Examples include congenital diabetes due to genetic defects of insulin secretion, cystic fibrosis-related diabetes, steroid diabetes induced by high doses of glucocorticoids, and several forms of [[MODY|monogenic diabetes]].
All forms of diabetes have been treatable since [[insulin]] became medically available in 1921, but there is no cure for the common types except a [[pancreas transplant]], although gestational diabetes usually resolves after delivery. Diabetes and its treatments can cause many complications. [[Acute (medical)|Acute]] complications including [[hypoglycemia]], [[diabetic ketoacidosis]], or [[nonketotic hyperosmolar coma]] may occur if the disease is not adequately controlled. Serious long-term complications include [[cardiovascular disease]], [[chronic renal failure]], [[diabetic retinopathy|retinal damage]], which can lead to [[blindness]], several types of [[diabetic neuropathy|nerve damage]], and microvascular damage, which may cause [[erectile dysfunction]] and poor wound healing. Poor healing of wounds, particularly of the feet, can lead to [[gangrene]], possibly requiring [[amputation]]. Adequate treatment of diabetes, as well as increased emphasis on [[blood pressure]] control and lifestyle factors such as not [[tobacco smoking|smoking]] and maintaining a healthy [[human weight|body weight]], may improve the risk profile of most of the chronic complications. In the developed world, diabetes is the most significant cause of adult blindness in the non-elderly and the leading cause of non-traumatic amputation in adults, and [[diabetic nephropathy]] is the main illness requiring [[renal dialysis]] in the United States.<ref>{{cite web|url=http://patients.uptodate.com/topic.asp?file=dialysis/15147|title=UpToDate Dialysis in diabetic nephropathy|accessdate=2007-12-07|last=Mailloux|first=Lionel|date=2007-02-13|publisher=UpToDate }}</ref>
== Classification ==
{{diabetes}}
The term ''diabetes'', without qualification, usually refers to diabetes mellitus, which roughly translates to excessive sweet urine (known as "[[glycosuria]]") but there are several rarer conditions also named diabetes. The most common of these is [[diabetes insipidus]] in which large amounts of urine are produced ([[polyuria]]), which is not sweet (insipidus meaning "without taste" in Latin); it can be caused either by [[kidney]] (nephrogenic DI) or [[pituitary gland]] (central DI) damage. It is a noninfectious disease. Among the body systems affected by Diabetes mellitus are the nervous, digestive, circulatory, endocrine and urinary systems, but all body systems are in some way affected.
The term "type 1 diabetes" has universally 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 non-insulin-dependent diabetes mellitus (NIDDM). Beyond these two types, there is no agreed-upon standard nomenclature. Various sources have defined "type 3 diabetes" as, among others, [[gestational diabetes]],<ref>{{cite web|url= http://www.diabetes.org/other-types.jsp|title=Other "types" of diabetes|publisher=[[American Diabetes Association]]|date=August 25, 2005}}</ref> insulin-resistant type 1 diabetes (or "double diabetes"), type 2 diabetes which has progressed to require injected insulin, and [[latent autoimmune diabetes]] of adults (or LADA or "[[Diabetes Type 1.5|type 1.5]]" diabetes.<ref>{{cite web|url=http://autoimmune.pathology.jhmi.edu/diseases.cfm?systemID=3&DiseaseID=23|title=Diseases: Johns Hopkins Autoimmune Disease Research Center|accessdate=2007-09-23|format=|work=}}</ref>)
=== Type 1 diabetes ===
{{Main|Diabetes mellitus type 1}}
[[Type 1 diabetes mellitus]] is characterized by loss of the insulin-producing [[beta cell]]s of the [[islets of Langerhans]] in the pancreas leading to a deficiency of insulin. This type of diabetes can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, where beta cell loss is a [[T-cell]] mediated [[autoimmunity|autoimmune]] attack.<ref name="Rother">{{cite journal|last=Rother|first=KI|year=2007|title=Diabetes Treatment — Bridging the Divide|journal=N Engl J Med|volume=356|issue=15|pages=1499–1501|url=http://content.nejm.org/cgi/content/full/356/15/1499|doi=10.1056/NEJMp078030|pmid=17429082}}</ref> There is no known preventive measure which can be taken against type 1 diabetes, which contain approximately 10% of diabetes mellitus cases in North America and Europe (though this varies by geographical location). 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 it represents a majority of the diabetes cases in children.
The principal treatment of type 1 diabetes, even in its earliest stages, is the delivery of artificial insulin via injection combined with careful monitoring of blood glucose levels using blood testing monitors. Without insulin, [[diabetic ketoacidosis]] often develops which may result in coma or death. Treatment emphasis is now also placed on lifestyle adjustments (diet and exercise) though these cannot reverse the progress of the disease. Apart from the common [[subcutaneous]] injections, it is also possible to deliver insulin by a [[insulin pump|pump]], which allows continuous infusion of insulin 24 hours a day at preset levels, and the ability to program doses (a [[Bolus (medicine)|bolus]]) of insulin as needed at meal times. An inhaled form of insulin was approved by the FDA in January 2006, although it was discontinued for business reasons in October 2007.<ref>{{cite web|url=http://www.fda.gov/bbs/topics/news/2006/NEW01304.html|title=FDA Approves First Ever Inhaled Insulin Combination Product for Treatment of Diabetes|accessdate=2007-09-09|work=}}</ref><ref>{{cite web|url=http://www.mannkindcorp.com/pressreleasetext.aspx?releaseID=1198182|title=MannKind Unveils Proposed Trade Name at Dedication of Danbury Manufacturing Facility|accessdate=2008-10-23|format=|work=}}</ref> Non-insulin treatments, such as [[monoclonal antibodies]] and [[stem-cell]] based therapies, are effective in animal models but have not yet completed clinical trials in humans.<ref>{{cite web|url=http://www.cliniclog.com/type_1_diabetes_trials.php|title=ClinicLog article on current diabetes trials.|accessdate=2008-07-23|last=Baillie|first=K|date=2008-07-05|publisher=ClinicLog.com }}</ref>
Type 1 treatment must be continued indefinitely in essentially all cases. The longest surviving Type I diabetes patient is [[Gladys Dull]], who has lived with the condition for over 83 years. Treatment need not significantly impair normal activities, if sufficient patient training, awareness, appropriate care, discipline in testing and dosing of insulin is taken. However, treatment is burdensome for patients; insulin is replaced in a non-physiological manner, and this approach is therefore far from ideal. The average glucose level for the type 1 patient should be as close to normal (80–120 mg/dl, 4–6 [[milli|m]][[Mole (unit)|mol]]/[[Litre|L]]) as is ''safely'' 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 400 mg/dl (20 mmol/L) are sometimes accompanied by discomfort and frequent urination leading to [[dehydration]]. Values above 600 mg/dl (30 mmol/L) usually require medical treatment and may lead to [[ketoacidosis]], although they are not immediately life-threatening. However, low levels of blood glucose, called [[hypoglycemia]], may lead to seizures or episodes of unconsciousness and absolutely must be treated immediately, via emergency high-glucose gel placed in the patient's mouth, intravenous administration of dextrose, or an injection of [[glucagon]].
=== Type 2 diabetes ===
{{Main|Diabetes mellitus type 2}}
Type 2 diabetes mellitus is characterized differently and is due to insulin resistance or reduced insulin sensitivity, combined with relatively reduced insulin secretion which in some cases becomes absolute. The defective responsiveness of body tissues to insulin almost certainly involves the [[insulin receptor]] in cell membranes. However, the specific defects are not known. Diabetes mellitus due to a known specific defect are classified separately. Type 2 diabetes is the most common type.
In the early stage of type 2 diabetes, the predominant abnormality is reduced insulin sensitivity, characterized by elevated levels of insulin in the blood. At this stage hyperglycemia can be reversed by a variety of measures and [[Anti-diabetic drug|medications]] that improve insulin sensitivity or reduce glucose production by the [[liver]]. 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 in type 2 diabetes. [[Central obesity]] (fat concentrated around the waist in relation to abdominal organs, but not subcutaneous fat) is known to predispose individuals to insulin resistance. Abdominal fat is especially active hormonally, secreting a group of hormones called [[adipokine]]s that may possibly impair glucose tolerance. Obesity is found in approximately 55% of patients diagnosed with type 2 diabetes.<ref>{{cite journal|author=Eberhart MS, Ogden C, Engelgau M, Cadwell B, Hedley AA, Saydah SH|title=Prevalence of overweight and obesity among adults with diagnosed diabetes—United States, 1988-1994 and 1999-2002|journal=MMWR Morb. Mortal. Wkly. Rep.|volume=53|issue=45|pages=1066–8|year=2004|month=November|pmid=15549021|url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5345a2.htm}}</ref> Other factors include aging (about 20% of elderly patients in North America have diabetes) and family history (type 2 is much more common in those with close relatives who have had it). In the last decade, type 2 diabetes has increasingly begun to affect children and adolescents, probably in connection with the increased prevalence of childhood obesity seen in recent decades in some places.<ref>{{cite book|last=Arlan Rosenbloom|first=Janet H Silverstein|title=Type 2 Diabetes in Children and Adolescents: A Clinician's Guide to Diagnosis, Epidemiology, Pathogenesis, Prevention, and Treatment|publisher=American Diabetes Association,U.S.|year=2003|pages=1|isbn=978-1580401555}}</ref> Environmental exposures may contribute to recent increases in the rate of type 2 diabetes. A positive correlation has been found between the concentration in the urine of [[bisphenol A]], a constituent of polycarbonate plastic from some producers, and the incidence of type 2 diabetes.<ref>{{cite journal|author=Lang IA, Galloway TS, Scarlett A, ''et al.''|title=Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults|journal=JAMA|volume=300|issue=11|pages=1303–10|year=2008|month=September|pmid=18799442|doi=10.1001/jama.300.11.1303 }}</ref>
Type 2 diabetes may go unnoticed for years because visible symptoms are typically mild, non-existent or sporadic, and usually there are no [[Diabetic ketoacidosis|ketoacidotic episodes]]. However, severe long-term complications can result from unnoticed type 2 diabetes, including [[renal failure]] due to [[diabetic nephropathy]], vascular disease (including [[coronary artery disease]]), vision damage due to [[diabetic retinopathy]], loss of sensation or pain due to [[diabetic neuropathy]], liver damage from [[non-alcoholic steatohepatitis]] and heart failure from [[diabetic cardiomyopathy]].
Type 2 diabetes is usually first treated by increasing physical activity, decreasing [[carbohydrate]] intake, and [[weight loss|losing weight]]. 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. It is sometimes possible to achieve long-term, satisfactory glucose control with these measures alone. However, the underlying tendency to insulin resistance is not lost, and so attention to diet, exercise, and weight loss must continue. The usual next step, if necessary, is treatment with oral [[antidiabetic drug]]s. Insulin production is initially only moderately impaired in type 2 diabetes, so oral medication (often used in various combinations) can be used to improve insulin production (e.g., [[sulfonylureas]]), to regulate inappropriate release of glucose by the liver and attenuate insulin resistance to some extent (e.g., [[metformin]]), and to substantially attenuate insulin resistance (e.g., [[thiazolidinedione]]s). According to one study, overweight patients treated with metformin compared with diet alone, had [[relative risk reduction]]s of 32% for any diabetes endpoint, 42% for diabetes related death and 36% for all cause mortality and stroke.<ref>{{cite journal|author=|title=Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group|journal=Lancet|volume=352|issue=9131|pages=854–65|year=1998|pmid=9742977|doi=10.1016/S0140-6736(98)07037-8}}</ref> Oral medication may eventually fail due to further impairment of beta cell insulin secretion. At this point, insulin therapy is necessary to maintain normal or near normal glucose levels.
=== Gestational diabetes ===
{{Main|Gestational diabetes}}
Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2%–5% of all [[pregnancy|pregnancies]] and may improve or disappear after delivery. Gestational diabetes is fully treatable but requires careful medical supervision throughout the pregnancy. About 20%–50% of affected women develop type 2 diabetes later in life.
Even 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 [[Infant respiratory distress syndrome|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. [[Induction (birth)|Induction]] may be indicated with decreased placental function. A [[Caesarean section|cesarean section]] may be performed if there is marked fetal distress or an increased risk of injury associated with [[macrosomia]], such as [[shoulder dystocia]].
A 2008 study completed in the U.S. found that more American women are entering pregnancy with preexisting diabetes. In fact the rate of diabetes in expectant mothers has more than doubled in the past 6 years.<ref>{{cite journal|author=Lawrence JM, Contreras R, Chen W, Sacks DA|title=Trends in the prevalence of preexisting diabetes and gestational diabetes mellitus among a racially/ethnically diverse population of pregnant women, 1999-2005|journal=Diabetes Care|volume=31|issue=5|pages=899–904|year=2008|month=May|pmid=18223030|doi=10.2337/dc07-2345}}</ref> This is particularly problematic as diabetes raises the risk of complications during pregnancy, as well as increasing the potential that the children of diabetic mothers will also become diabetic in the future.
=== Other types ===
Most cases of diabetes mellitus fall into the two broad [[etiologic]] categories of type 1 or type 2 diabetes. However, many types of diabetes mellitus have more specific known causes, and thus fall into more specific categories. As more research is done into diabetes, many patients who were previously diagnosed as type 1 or type 2 diabetes will have their condition reclassified.
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 dominant|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.<ref name="WHO1999-DefDiagClass">{{cite web|author=[[World Health Organisation]] Department of Noncommunicable Disease Surveillance|title=Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications|year=1999|url=http://whqlibdoc.who.int/hq/1999/WHO_NCD_NCS_99.2.pdf|format=PDF}}</ref>
== Signs and symptoms ==
[[File:Main symptoms of diabetes.png|thumb|right|260px|Overview of the most significant symptoms of diabetes.]]
The classical symptoms are [[polyuria]] and [[polydipsia]] which are, respectively, frequent urination and increased thirst and consequent increased fluid intake. Symptoms may develop quite rapidly (weeks or months) in type 1 diabetes, particularly in children. However, in type 2 diabetes symptoms usually develop much more slowly and may be subtle or completely absent. Type 1 diabetes may also cause a rapid yet significant weight loss (despite normal or even increased eating) and irreducible [[mental fatigue]]. All of these symptoms except weight loss can also manifest in type 2 diabetes in patients whose diabetes is poorly controlled, although unexplained weight loss may be experienced at the onset of the disease. Final diagnosis is made by measuring the blood glucose concentration.
When the glucose concentration in the blood is raised beyond its [[renal threshold]] (about 10mmol/L, although this may be altered in certain conditions, such as pregnancy), [[reabsorption]] of glucose in the [[proximal tubule|proximal renal tubuli]] is incomplete, and part of the glucose remains in the [[urine]] ([[glycosuria]]). This increases the [[osmotic pressure]] of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production ([[polyuria]]) and increased fluid loss. Lost blood volume will be replaced osmotically from water held in body cells and other body compartments, causing [[dehydration]] and increased thirst.
Prolonged high blood glucose causes glucose absorption, which leads to changes in the shape of the lenses of the eyes, resulting in vision changes; sustained sensible glucose control usually returns the lens to its original shape. Blurred vision is a common complaint leading to a diabetes diagnosis; type 1 should always be suspected in cases of rapid vision change, whereas with type 2 change is generally more gradual, but should still be suspected.
Patients (usually with type 1 diabetes) may also initially present with diabetic ketoacidosis (DKA), an extreme state of metabolic dysregulation characterized by the smell of [[acetone]] on the patient's breath; a rapid, deep breathing known as [[Kussmaul breathing]]; [[polyuria]]; nausea; vomiting and [[abdominal pain]]; and any of many altered states of consciousness or arousal (such as hostility and mania or, equally, confusion and lethargy). In severe DKA, [[coma]] may follow, progressing to death. Diabetic ketoacidosis is a medical emergency and requires immediate hospitalization.
A rarer but equally severe possibility is [[Nonketotic hyperosmolar coma|hyperosmolar nonketotic state]], which is more common in type 2 diabetes and is mainly the result of dehydration due to loss of body water. Often, the patient has been drinking extreme amounts of sugar-containing drinks, leading to a [[positive feedback|vicious circle]] in regard to the water loss.
== 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, with some evidence pointing at [[Coxsackie B4 virus]]. There is a genetic element in individual susceptibility to some of these triggers which has been traced to particular [[Human leukocyte antigen|HLA]] [[genotype]]s (i.e., the genetic "self" identifiers relied upon by the immune system). However, even in those who have inherited the susceptibility, type 1 diabetes mellitus seems to require an environmental trigger.
There is a stronger inheritance pattern for type 2 diabetes. Those with first-degree relatives with type 2 have a much higher risk of developing type 2, increasing with the number of those relatives. [[Concordance (genetics)|Concordance]] among [[Twin#Identical twins|monozygotic twins]] is close to 100%, and about 25% of those with the disease have a family history of diabetes. Genes significantly associated with developing type 2 diabetes, include ''[[TCF7L2]]'', ''[[PPARG]]'', ''[[FTO gene|FTO]]'', ''[[KCNJ11]]'', ''[[NOTCH2]]'', ''[[WFS1]]'', ''[[CDKAL1]]'', ''[[IGF2BP2]]'', ''[[SLC30A8]]'', ''[[JAZF1]]'', and ''[[HHEX]]''.<ref>{{cite journal|author=Lyssenko V, Jonsson A, Almgren P, ''et al.''|title=Clinical risk factors, DNA variants, and the development of type 2 diabetes|journal=N. Engl. J. Med.|volume=359|issue=21|pages=2220–32|year=2008|month=November|pmid=19020324|doi=10.1056/NEJMoa0801869 }}</ref> ''KCNJ11'' ([[Inward-rectifier potassium ion channel|potassium inwardly rectifying channel]], subfamily J, member 11), encodes the islet ATP-sensitive potassium channel Kir6.2, and ''TCF7L2'' (transcription factor 7–like 2) regulates [[proglucagon]] gene expression and thus the production of [[glucagon-like peptide-1]].<ref name="Rother" /> Moreover, obesity (which is an independent risk factor for type 2 diabetes) is strongly inherited.<ref>{{cite journal|author=Walley AJ, Blakemore AI, Froguel P|title=Genetics of obesity and the prediction of risk for health|journal=Hum. Mol. Genet.|volume=15|issue=Spec No 2|pages=R124–30|year=2006|pmid=16987875|doi=10.1093/hmg/ddl215}}</ref>
[[genetic disorder|Monogenic]] forms, e.g., [[maturity onset diabetes of the young|MODY]], constitute 1-5 % of all cases.<ref>{{cite news|first=|last=|coauthors=|title=Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-onset Diabetes of the Young|date=|publisher=National Institute of Diabetes and Digestive and Kidney Diseases, NIH|url =http://www.diabetes.niddk.nih.gov/dm/pubs/mody/|work =National Diabetes Information Clearinghouse (NDIC)|accessdate=2008-08-04 }}</ref>
Various hereditary conditions may feature diabetes, for example [[myotonic dystrophy]] and [[Friedreich's ataxia]]. [[Wolfram's syndrome]] is an [[autosomal recessive]] [[neurodegenerative disorder]] that first becomes evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD.<ref name="AMN">{{cite journal|author=Barrett TG|title=Mitochondrial diabetes, DIDMOAD and other inherited diabetes syndromes|journal=Best Pract. Res. Clin. Endocrinol. Metab.|volume=15|issue=3|pages=325–43|year=2001|pmid=11554774|doi=10.1053/beem.2001.0149}}</ref>
== Pathophysiology ==
[[Image:Glucose-insulin-release.png|right|thumb|400px|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 primarily triggered by food, chiefly food containing absorbable glucose. The chief trigger is a rise in blood glucose levels after eating]]
Insulin is the principal hormone that regulates uptake of [[glucose]] from the blood into most cells (primarily muscle and fat cells, but not central nervous system cells). Therefore deficiency of insulin or the insensitivity of its [[Receptor (biochemistry)|receptors]] plays a central role in all forms of diabetes mellitus.
Most of the carbohydrates in food are converted within a few hours to the [[monosaccharide]] [[glucose]], the principal carbohydrate found in blood and used by the body as fuel. The most significant exceptions are [[fructose]], most disaccharides (except [[sucrose]] and in some people [[lactose]]), and all more complex polysaccharides, with the outstanding exception of [[starch]]. Insulin is released into the blood by beta cells (β-cells), found in the Islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the body's cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage.
Insulin is also the principal control signal for conversion of glucose to [[glycogen]] for internal storage in liver and muscle cells. Lowered glucose levels result both in the reduced release of insulin from the beta cells and in the reverse conversion of glycogen to glucose when glucose levels fall. This is mainly controlled by the hormone [[glucagon]] which acts in an opposite manner to insulin. Glucose thus recovered by the liver re-enters the bloodstream; muscle cells lack the necessary export mechanism.
Higher insulin levels increase some [[anabolism|anabolic]] ("building up") processes such as cell growth and duplication, [[protein biosynthesis|protein synthesis]], and [[lipid|fat]] storage. Insulin (or its lack) is the principal signal in converting many of the bidirectional processes of metabolism from a [[catabolism|catabolic]] to an anabolic direction, and vice versa. In particular, a low insulin level is the trigger for entering or leaving ketosis (the fat burning metabolic phase).
If the amount of insulin available is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or [[insulin resistance|resistance]]), or if the insulin itself is defective, then glucose will not be absorbed properly by those body cells that require it nor will it be stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as [[acidosis]].
== Diagnosis ==
{{Refimprove|section|date=October 2009}}
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 a quarter of people with new type 1 diabetes have developed some degree of diabetic [[ketoacidosis]](Ketoacidosis is a type of metabolic acidosis which is caused by high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids.) by the time the diabetes is recognized. The diagnosis of other types of diabetes is usually made in other ways. These include ordinary health screening; detection of hyperglycemia during other medical investigations; and secondary symptoms such as vision changes or unexplainable fatigue. Diabetes is often detected when a person suffers a problem that is frequently caused by diabetes, such as a [[myocardial infarction|heart attack]], [[stroke]], [[neuropathy]], poor wound healing or a foot ulcer, certain eye problems, certain [[fungal infection]]s, or delivering a baby with [[macrosomia]] or [[hypoglycemia]].
Diabetes mellitus is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of the following:<ref name="WHO1999-DefDiagClass" />
* Fasting plasma glucose level at or above 126 mg/dL (7.0 mmol/L).
* [[Plasma glucose]] at or above 200 mg/dL (11.1 mmol/L) two hours after a 75 g oral glucose load as in a [[glucose tolerance test]].
* Symptoms of hyperglycemia and casual plasma glucose at or above 200 mg/dL (11.1 mmol/L).
A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above-listed methods on a different day. Most physicians prefer 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.<ref>{{cite journal|author=Saydah SH, Miret M, Sung J, Varas C, Gause D, Brancati FL|journal=Diabetes Care|year=2001|volume=24|issue=8|pages=1397–402|title=Postchallenge hyperglycemia and mortality in a national sample of U.S. adults|pmid=11473076 |doi=10.2337/diacare.24.8.1397}}</ref> According to the current definition, two fasting glucose measurements above 126 mg/dL (7.0 mmol/L) is considered diagnostic for diabetes mellitus.
Patients with fasting glucose levels from 100 to 125 mg/dL (6.1 and 7.0 mmol/L) are considered to have [[impaired fasting glycemia|impaired fasting glucose]]. Patients with plasma glucose at or above 140 mg/dL or 7.8 mmol/L, but not over 200, two hours after a 75 g oral glucose load are considered to have [[impaired glucose tolerance]]. Of these two pre-diabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus as well as cardiovascular disease.<ref>{{cite web|author=Santaguida PL, Balion C, Hunt D, Morrison K, Gerstein H, Raina P, Booker L, Yazdi H|url=http://www.ahrq.gov/clinic/epcsums/impglusum.htm|title=Diagnosis, Prognosis, and Treatment of Impaired Glucose Tolerance and Impaired Fasting Glucose|work=Summary of Evidence Report/Technology Assessment, No. 128|publisher=[[Agency for Healthcare Research and Quality]]|accessdate=2008-07-20}}</ref>
While not used for diagnosis, an elevated level of glucose irreversibly bound to [[hemoglobin]] (termed [[glycated hemoglobin]] or ''HbA1c'') of 6.0% or higher (the 2003 revised U.S. standard) is considered abnormal by most labs; HbA1c is primarily used as a treatment-tracking test reflecting average blood glucose levels over the preceding 90 days (approximately) which is the average lifetime of red blood cells which contain hemoglobin in most patients. 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 6.5%.<ref>{{cite journal|last=Sniderman|first=AD|coauthors=Bhopal R, Prabhakaran D, Sarrafzadegan N, Tchernof A|title=Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis|journal=International journal of epidemiology|volume=36|issue=1|pages=220–5|year=2007|pmid=17510078|doi=10.1093/ije/dyl245}}</ref><ref>{{cite journal|author=Genuth S|title=Insights from the diabetes control and complications trial/epidemiology of diabetes interventions and complications study on the use of intensive glycemic treatment to reduce the risk of complications of type 1 diabetes|journal=Endocr Pract|issn=1530-891X|volume=12|issue=Suppl 1|pages=34–41|year =2006|month=Jan-Feb|pmid=16627378}}</ref>
== Screening ==
Diabetes screening is recommended for many people at various stages of life, and for those with any of several [[risk factors]]. The screening test varies according to circumstances and local policy, and may be a random blood glucose test, a fasting blood glucose test, a blood glucose test two hours after 75 g of glucose, or an even more formal [[glucose tolerance test]]. Many healthcare providers recommend universal screening for adults at age 40 or 50, and often periodically thereafter. Earlier screening is typically recommended for those with risk factors such as obesity, [[family history (medicine)|family history]] of diabetes, high-risk [[ethnicity]] ([[Hispanic]], [[Indigenous peoples of the Americas|Native American]], [[African diaspora|Afro-Caribbean]], [[Pacific Islander]], or [[Maori]]).<ref name="pmid17215197">{{cite journal|author=Lee CM, Huxley RR, Lam TH, Martiniuk AL, Ueshema H, Pan WH, Welborn T, Woodward M; Asia Pacific Cohort Studies Collaboration|title=Prevalence of diabetes mellitus and population attributable fractions for coronary heart disease and stroke mortality in the WHO South-East Asia and Western Pacific regions|journal=Asia Pac J Clin Nutr|volume=16|issue=1|pages=187–92|year=2007|pmid=17215197 }}</ref><ref name="pmid10889785">{{cite journal|author=Seidell JC|title=Obesity, insulin resistance and diabetes--a worldwide epidemic|journal=Br. J. Nutr.|volume=83 Suppl 1|issue=|pages=S5–8|year=2000|pmid=10889785 }}</ref>
Many medical conditions are associated with diabetes and warrant screening. A partial list includes: high blood pressure, [[dyslipidemia|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. The risk of diabetes is higher with chronic use of several medications, including high-dose [[glucocorticoid]]s, some [[chemotherapy]] agents (especially [[L-asparaginase]]), as well as some of the antipsychotics and mood stabilizers (especially [[phenothiazine]]s and some [[atypical antipsychotics]]).
People with a confirmed diagnosis of diabetes are tested routinely for complications. This includes yearly urine testing for [[microalbuminuria]] and examination of the [[retina]] of the eye for retinopathy.
== Prevention ==
Type 1 diabetes risk is known to depend upon a genetic predisposition based on [[Human leukocyte antigen|HLA]] types (particularly types DR3 and DR4), an unknown environmental trigger (suspected to be an infection, although none has proven definitive in all cases), and an uncontrolled [[autoimmune]] response that attacks the insulin producing [[beta cells]].<ref>{{cite journal|author=Daneman D|title=Type 1 diabetes|journal=Lancet|volume=367|issue=9513|pages=847–58|year=2006|pmid=16530579|doi=10.1016/S0140-6736(06)68341-4}}</ref> Some research has suggested that [[breastfeeding]] decreased the risk in later life;<ref>{{cite journal|author=Borch-Johnsen K, Joner G, Mandrup-Poulsen T, Christy M, Zachau-Christiansen B, Kastrup K, Nerup J|title=Relation between breast-feeding and incidence rates of insulin-dependent diabetes mellitus. A hypothesis|journal=Lancet|volume=2|issue=8411|pages=1083–6|year=1984|pmid=6150150|doi=10.1016/S0140-6736(84)91517-4}}</ref><ref>{{cite journal|author=Naim Shehadeh, Raanan Shamir, Moshe Berant, Amos Etzioni|title=Insulin in human milk and the prevention of type 1 diabetes|journal=Pediatric Diabetes|volume=2|issue=4|pages=175–7|year=2001|url=http://www.blackwell-synergy.com/doi/abs/10.1034/j.1399-5448.2001.20406.x?journalCode=pdi|doi=10.1034/j.1399-5448.2001.20406.x}}</ref> various other nutritional risk factors are being studied, but no firm evidence has been found.<ref>{{cite journal|author=Virtanen S, Knip M|title=Nutritional risk predictors of beta cell autoimmunity and type 1 diabetes at a young age|journal=Am J Clin Nutr|volume=78|issue=6|pages=1053–67|year=2003|pmid=14668264}}</ref>
Giving children 2000 IU of [[Vitamin D]] during their first year of life is associated with reduced risk of type 1 diabetes, though the causal relationship is obscure.<ref>{{cite journal|author=Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM|title=Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study|journal=Lancet|year=2001|pmid=11705562|volume=358|page=1500|doi=10.1016/S0140-6736(01)06580-1}}</ref>
Children with antibodies to beta cell proteins (ie at early stages of an immune reaction to them) but no overt diabetes, and treated with vitamin B-3 ([[niacin]]), had less than half the diabetes onset incidence in a 7-year time span as did the general population, and an even lower incidence relative to those with antibodies as above, but who received no vitamin B3.<ref name="pmid8961125">{{cite journal|author=Elliott RB, Pilcher CC, Fergusson DM, Stewart AW|title=A population based strategy to prevent insulin-dependent diabetes using nicotinamide|journal=J. Pediatr. Endocrinol. Metab.|volume=9|issue=5|pages=501–9|year=1996|month=Sep-Oct|pmid=8961125 }}</ref>
Type 2 diabetes risk can be reduced in many cases by making changes in diet and increasing physical activity.<ref name="pmid17098085">{{cite journal|author=Lindström J, Ilanne-Parikka P, Peltonen M, Aunola S, Eriksson J, Hemiö K, Hämäläinen H, Härkönen P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Mannelin M, Paturi M, Sundvall J, Valle T, Uusitupa M, Tuomilehto J|title=Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study|journal=Lancet|volume=368|issue=9548|pages=1673–9|year=2006|pmid=17098085|doi=10.1016/S0140-6736(06)69701-8}}</ref><ref name="Knowler">{{cite journal|author=Knowler W, Barrett-Connor E, Fowler S, Hamman R, Lachin J, Walker E, Nathan D|title=Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin|journal=N Engl J Med|volume=346|issue=6|pages=393–403|year=2002|pmid=11832527|doi=10.1056/NEJMoa012512}}</ref> The [[American Diabetes Association]] (ADA) recommends maintaining a healthy weight, getting at least 2½ hours of exercise per week (several brisk sustained walks appear sufficient), having a modest fat intake, and eating sufficient fiber (e.g., from whole grains). The ADA does not recommend [[Alcohol consumption and health|alcohol consumption]] as a preventive, but it is interesting to note that moderate alcohol intake may reduce the risk (though heavy consumption absolutely and clearly increases damage to bodily systems significantly); a similarly confused connection between low dose alcohol consumption and heart disease is termed the [[French Paradox]].
There is inadequate evidence that eating foods of low [[glycemic index]] is clinically helpful despite recommendations and suggested diets emphasizing this approach.<ref>{{cite journal|author=Bantle JP, Wylie-Rosett J, Albright AL, ''et al.''|title=Nutrition recommendations and interventions for diabetes--2006: a position statement of the American Diabetes Association|journal=Diabetes Care|volume=29|issue=9|pages=2140–57|year=2006|pmid=16936169|doi=10.2337/dc06-9914|url=http://care.diabetesjournals.org/cgi/content/full/29/9/2140}}</ref>
Diets that are very low in saturated fats reduce the risk of becoming insulin resistant and diabetic.<ref name="Barnard 2007">{{cite book|last=Barnard|first=Neal|coauthors=|year=2007|chapter=13|title=Dr. Neal Barnard's Program for Reversing Diabetes: The Scientifically Proven System for Reversing Diabetes Without Drugs|publisher=Rodale/Holtzbrinck Publishers|location=New York, NY|isbn=13 978-1-59486-528-2}}</ref><ref name="Barnard ND, Katcher HI, Jenkins DJ, Cohen J, Turner-McGrievy G 2009">{{cite journal|author=Barnard ND, Katcher HI, Jenkins DJ, Cohen J, Turner-McGrievy G|title=Vegetarian and vegan diets in type 2 diabetes management|journal=Nutr Rev|year=2009|pmid=19386029|url=http://www.ncbi.nlm.nih.gov/pubmed/19386029?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum}}</ref> Study group participants whose "physical activity level and dietary, smoking, and alcohol habits were all in the low-risk group had an 82% lower incidence of diabetes.".<ref>{{cite journal|author=Mozaffarian D, Kamineni A, Carnethon M, Djoussé L, Mukamal KJ, Siscovick D|title=Lifestyle risk factors and new-onset diabetes mellitus in older adults: the cardiovascular health study|journal=Arch Intern Med.|year=2009|pmid=19398692|url=http://www.ncbi.nlm.nih.gov/pubmed/19398692?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum}}</ref> In another study of dietary practice and incidence of diabetes, "foods rich in vegetable oils, including non-hydrogenated margarines, nuts, and seeds, should replace foods rich in saturated fats from meats and fat-rich dairy products. Consumption of partially hydrogenated fats should be minimized."<ref>{{cite journal|author=Risérus U, Willett WC, Hu FB|title=Dietary fats and prevention of type 2 diabetes|journal= Prog Lipid Res|year=2009|pmid=19032965|url=http://www.ncbi.nlm.nih.gov/pubmed/19032965?ordinalpos=20&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum}}</ref>
There are numerous studies which suggest connections between some aspects of Type II diabetes with ingestion of certain foods or with some drugs. Some studies have shown delayed progression to diabetes in predisposed patients through prophylactic use of metformin,<ref name="Knowler" /> [[rosiglitazone]],<ref>{{cite journal|author=Gerstein H, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, Hanefeld M, Hoogwerf B, Laakso M, Mohan V, Shaw J, Zinman B, Holman R|title=Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial|journal=Lancet|volume=368|issue=9541|pages=1096–105|year=2006|pmid=16997664|doi=10.1016/S0140-6736(06)69420-8}}</ref> or [[valsartan]].<ref>{{cite journal|author =Kjeldsen SE, Julius S, Mancia G, McInnes GT, Hua T, Weber MA, Coca A, Ekman S, Girerd X, Jamerson K, Larochelle P, Macdonald TM, Schmieder RE, Schork MA, Stolt P, Viskoper R, Widimsky J, Zanchetti A; for the VALUE Trial Investigators|title=Effects of valsartan compared to amlodipine on preventing type 2 diabetes in high-risk hypertensive patients: the VALUE trial|journal=J Hypertens|volume=24|issue=7|pages=1405–12|year=2006|pmid=16794491|doi=10.1097/01.hjh.0000234122.55895.5b}}</ref> In patients on [[hydroxychloroquine]] for [[rheumatoid arthritis]], incidence of diabetes was reduced by 77% though causal mechanisms are unclear.<ref>{{cite journal|author=Wasko MC, Hubert HB, Lingala VB, ''et al.''|title=Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis|journal=JAMA|volume=298|issue=2|pages=187–93|year=2007|pmid=17622600|doi=10.1001/jama.298.2.187}}</ref>
Breastfeeding may also be associated with the prevention of type 2 of the disease in mothers.<ref name="JAMA2005-Stuebe">{{cite journal|author=Stuebe AM, Rich-Edwards JW, Willett WC, Manson JE, Michels KB|title=Duration of lactation and incidence of type 2 diabetes|journal=JAMA|year=2005|pages=2601–10|volume=294|issue=20|pmid=16304074|doi=10.1001/jama.294.20.2601}}</ref> Clear evidence for these and any of many other connections between foods and supplements and diabetes is sparse to date; none, despite secondary claims for (or against), is sufficiently well established to justify as a standard clinical approach.
== Treatment and management ==
{{Main|Diabetes management}}
Diabetes mellitus is currently a [[chronic disease]] with no cure. Medical emphasis must necessarily be on managing/avoiding possible short-term as well as long-term diabetes-related problems. There is an exceptionally important role for patient education, dietetic support, sensible exercise, self monitoring of blood glucose, with the goal of keeping both short-term and long-term blood glucose levels [[Diabetes management#Glycemic control|within acceptable bounds]]. Careful control is needed to reduce the risk of long term complications. This is theoretically achievable with combinations of diet, exercise and weight loss (type 2), various oral diabetic drugs (type 2 only), and insulin use (type 1 and for type 2 not responding to oral medications, mostly those with extended duration diabetes). In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications should be undertaken to control blood pressure<ref>{{cite journal|last=Adler|first=A.I.|coauthors=Stratton, I. M.; Neil, H.A.; ''et al.''|title=Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study|pmc=27454|journal=BMJ|volume=321|issue=7258|pages=412–9|year=2000|pmid=10938049|doi=10.1136/bmj.321.7258.412}}</ref> and cholesterol by exercising more, smoking less or ideally [[smoking cessation|not at all]], consuming an appropriate [[Diabetic diet|diet]], wearing [[diabetic sock]]s, wearing diabetic shoes, and if necessary, taking any of several drugs to reduce blood pressure. Many type 1 treatments include combination use of regular or NPH insulin, and/or synthetic insulin analogs (e.g., Humalog, Novolog or Apidra) in combinations such as Lantus/Levemir and Humalog, Novolog or Apidra. Another type 1 treatment option is the use of the insulin pump (e.g., from Deltec Cozmo, Animas, Medtronic Minimed, Insulet Omnipod, or ACCU-CHEK). A [[blood lancet]] is used to pierce the skin (typically of a finger), in order to draw blood to test it for sugar levels.
In countries using a [[general practitioner]] system, such as the [[United Kingdom]], care may take place mainly outside hospitals, with hospital-based specialist care used only in case of complications, difficult blood sugar control, or research projects. In other circumstances, general practitioners and specialists share care of a patient in a team approach. [[Optometry|Optometrists]], [[podiatry|podiatrists]]/chiropodists, [[dietitian]]s, [[Physical therapy|physiotherapists]], nursing specialists (e.g., DSNs (Diabetic Specialist Nurse)), [[nurse practitioner]]s, or [[Certified diabetes educator|Certified Diabetes Educators]], may jointly provide multidisciplinary expertise. In countries where patients must provide for their own health care (e.g in the US, and in much of the undeveloped world), the impact of out-of-pocket costs of adequate diabetic care can be very high. In addition to the medications and supplies needed, patients are often advised to receive regular consultation from a physician (e.g., at least every three to six months) although research is underway to develop [[artificial intelligence]] systems which may reduce the frequency of such visits.<ref name="walker">{{cite web |last=Walker |first=Donald |title=Similarity Determination and Case Retrieval in an Intelligent Decision Support System for Diabetes Management |month=November |year=2007 |url=http://etd.ohiolink.edu/send-pdf.cgi/Walker%20Donald.pdf?acc_num=ohiou1194562654 |accessdate={{Date|2009-10-02|mdy}}}}</ref>
Oral administration of [[aloe vera]] might be a useful adjunct for lowering blood glucose in diabetic patients as well as for reducing blood lipid levels in patients with hyperlipidaemia. Ten controlled clinical trials were found to reach that conclusion in four independent literature searches. However, caveats reported in each study led the researchers to conclude that aloe vera's clinical effectiveness was not yet sufficiently defined in 1999.<ref>{{cite journal |author=Vogler BK, Ernst E |title=Aloe vera: a systematic review of its clinical effectiveness |journal=Br J Gen Pract |volume=49 |issue=447 |pages=823–8 |year=1999 |month=October |pmid=10885091 |pmc=1313538 |doi= |url=}}</ref>
[[Peer support]] links people living with diabetes. Within peer support, people with a common illness share knowledge and experience that others, including many health workers, do not have. Peer support is frequent, ongoing, accessible and flexible and can take many forms—phone calls, text messaging, group meetings, home visits, and even grocery shopping. It complements and enhances other health care services by creating the emotional, social and practical assistance necessary for managing disease and staying healthy.
== Cure ==
=== Cures for type 1 diabetes ===
{{Main|Cure for diabetes mellitus type 1}}
There is no practical cure, at this time, for type 1 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 beta cells in the Islets of Langerhans) has led to the study of several possible schemes to cure this form of diabetes mostly by replacing the pancreas or just the beta cells.<ref name="Vinik">{{cite journal|author=Vinik AI, Fishwick DT, Pittenger G|title=Advances in diabetes for the millennium: toward a cure for diabetes|journal=MedGenMed : Medscape general medicine|volume=6|issue=3 Suppl|page=12|year=2004|pmid=15647717 }}</ref> Only those type 1 diabetics who have received either a pancreas or a kidney-pancreas transplant (often when they have developed diabetic kidney disease (ie, nephropathy) and become insulin-independent) may now be considered "cured" from their diabetes. A simultaneous pancreas-kidney transplant is a promising solution, showing similar or improved survival rates over a kidney transplant alone.<ref name="Stratta">{{cite journal
| author=Stratta RJ, Alloway RR.|title=Pancreas transplantation for diabetes mellitus: a guide to recipient selection and optimum immunosuppression|journal=BioDrugs.|year=1998|pages=347–57|volume=10|issue=5|pmid=18020607
| doi=10.2165/00063030-199810050-00002 }}</ref> Still, they generally remain on long-term [[immunosuppressive drug]]s and there is a possibility that the immune system will mount a [[host versus graft]] response against the transplanted organ.<ref name="Vinik" />
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 partly due to the limited number of beta cell donors. Thus far, like any such transplant, it has provoked an immune reaction and long-term immunosuppressive drugs have been needed to protect the transplanted tissue.<ref>{{cite journal|author=Shapiro AM, Ricordi C, Hering BJ, ''et al.''|title=International trial of the Edmonton protocol for islet transplantation|journal=N. Engl. J. Med.|volume=355|issue=13|pages=1318–30|year=2006|pmid=17005949|doi=10.1056/NEJMoa061267}}</ref> An alternative technique has been proposed to place transplanted beta cells in a semi-permeable container, isolating and protecting them from the immune system. [[Stem cell research]] has also been suggested as a potential avenue for a cure since it may permit regrowth of Islet cells which are genetically part of the treated individual, thus perhaps eliminating the need for immuno-suppressants.<ref name="Vinik" />
This new method autologous nonmyeloablative hematopoietic stem cell transplantation was developed by a research team composed by Brazilian and American scientists (Dr. Julio Voltarelli, Dr. Carlos Eduardo Couri, Dr Richard Burt, and colleagues) and it was the first study to use stem cell therapy in human diabetes mellitus. This was initially tested in mice and in 2007 there was the first publication of stem cell therapy to treat this form of diabetes. Until 2009, there was 23 patients included and followed for a mean period of 29.8 months (ranging from 7 to 58 months). In the trial, severe immunosuppresion with high doses of cyclophosphamide and anti-thymocyte globulin is used with the aim of "turning off" the immunologic system", and then autologous hematopoietic stem cells are reinfused to regenerate a new one. In summary it is a kind of "immunologic reset" that blocks the autoimmune attack against residual pancreatic insulin-producing cells. Until December 2009, 12 patients remained continuously insulin-free for periods raging from 14 to 52 months and 8 patients became transiently insulin-free for periods ranging from 6 to 47 months. Of these last 8 patients, 2 became insulin-free again after the use of sitagliptin, a DPP-4 inhibitor approved only to treat type 2 diabetic patients and this is also the first study to document the use and complete insulin-independendce in humans with type 1 diabetes with this medication. In parallel with insulin suspension, indirect measures of endogenous insulin secretion revealed thate it significantly increased in the whole group of patients, regardless the need of daily exogenous insulin use. <ref>{{cite journal|author=Couri CE, Oliveira MC, Stracieri AB, ''et al.''|title=C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus|journal=JAMA|volume=301|issue=15|pages=1573–9|year=2009|month=April|pmid=19366777|doi=10.1001/jama.2009.470 }}</ref>
Microscopic or nanotechnological approaches are under investigation as well, in one proposed case with implanted stores of insulin metered out by a rapid response valve sensitive to blood glucose levels. At least two approaches have been demonstrated ''in vitro''. These are, in some sense, closed-loop insulin pumps.
=== Cures for type 2 diabetes ===
Type 2 diabetes is usually first treated by increasing physical activity, and eliminating [[saturated fat]] and reducing [[sugar]] and [[carbohydrate]] intake with a goal of [[weight loss|losing weight]]. 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. Diets that are very low in saturated fats can reverse insulin resistance.<ref name="Barnard 2007"/><ref name="Barnard ND, Katcher HI, Jenkins DJ, Cohen J, Turner-McGrievy G 2009"/>
Recently it has been shown that a type of [[gastric bypass surgery]] can normalize blood glucose levels in 80-100% of severely obese patients with diabetes. The precise causal mechanisms are being intensively researched; its results are not simply attributable to weight loss, as the improvement in blood sugars precedes any change in body mass. This approach may become a standard treatment for some people with type 2 diabetes in the relatively near future.<ref name="pmid12409659">{{cite journal|last=Rubino|first=F|coauthors=Gagner M|title=Potential of surgery for curing type 2 diabetes mellitus|journal=Ann. Surg.|volume=236|issue=5|pages=554–9|year=2002|pmid=12409659|pmc=1422611|doi=10.1097/00000658-200211000-00003}}</ref> This surgery has the additional benefit of reducing the death rate from all causes by up to 40% in severely obese people.<ref name="pmid17715409">{{cite journal|last=Adams|first=TD|coauthors=Gress RE, Smith SC, ''et al.''|title=Long-term mortality after gastric bypass surgery|journal=N. Engl. J. Med.|volume=357|issue=8|pages=753–61|year=2007|pmid=17715409|doi=10.1056/NEJMoa066603}}</ref> A small number of normal to moderately obese patients with type 2 diabetes have successfully undergone similar operations.<ref name="pmid17386401">{{cite journal|last=Cohen|first=RV|coauthors=Schiavon CA, Pinheiro JS, Correa JL, Rubino F|title=Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22-34 kg/m2: a report of 2 cases|journal=Surg Obes Relat Dis.|volume=3|issue=2|pages=195–7|year=2007|pmid=17386401|doi=10.1016/j.soard.2007.01.009}}</ref><ref name="NS">{{cite journal|last=Vasonconcelos|first=Alberto|date=2007-09-01|title= Could type 2 diabetes be reversed using surgery?
| journal=[[New Scientist]]|issue=2619|pages=11–3|url=http://www.newscientist.com/channel/health/mg19526193.100-could-type-2-diabetes-be-reversed-using-surgery.html|accessdate=2007-09-26}}</ref>
== Complications and prognosis ==
Patient education, understanding, and participation is vital since the complications of diabetes are far less common and less severe in people who have well-[[Diabetes management#Glycemic control|controlled]] blood sugar levels.<!--
--><ref>{{cite journal|last=Nathan|first=D.M.|coauthors=Cleary P.A., Backlund J.Y., ''et al.''|title=Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes|journal=N. Engl. J. Med.|volume=353|issue=25|pages=2643–53|year=2005|pmid=16371630|doi=10.1056/NEJMoa052187}}</ref><ref>{{cite journal|author=The Diabetes Control and Complications Trial Research Group|title=The effect of intensive diabetes therapy on the development and progression of neuropathy. The Diabetes Control and Complications Trial Research Group|journal=Ann. Intern. Med.|volume=122|issue=8|pages=561–8|year=1995|month=April|pmid=7887548|url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=7887548|day=15}}</ref>
Wider health problems accelerate the deleterious effects of diabetes. These include [[tobacco smoking|smoking]], [[hypercholesterolemia|elevated cholesterol]] levels, [[obesity]], [[hypertension|high blood pressure]], and lack of regular [[exercise]]. According to one study, women with high blood pressure (hypertension) were three times more likely to develop type 2 diabetes as compared with women with optimal BP after adjusting for various factors such as age, ethnicity, smoking, alcohol intake, body mass index (BMI), exercise, family history of diabetes, etc.<ref>"Women with high BP at three-fold risk of developing diabetes." TopNews.in July 1, 2009. http://www.topnews.in/women-high-bp-three-fold-risk-developing-diabetes-23341</ref> The study was conducted by researchers from the [[Brigham and Women’s Hospital]], [[Harvard Medical School]] and the [[Harvard School of Public Health]], USA, who followed over 38,000 female health professionals for ten years.
Anecdotal evidence suggests that some of those with type 2 diabetes who exercise regularly, lose weight, and eat healthy diets may be able to keep some of the disease or some of the effects of the disease in 'remission.' Certainly these tips can help prevent people predisposed to type 2 diabetes and those at pre-diabetic stages from actually developing the disorder as it helps restore insulin sensitivity. However patients should talk to their doctors about this for real expectations before undertaking it (esp. to avoid hypoglycemia or other complications); few people actually seem to go into total 'remission,' but some may find they need less of their insulin medications since the body tends to have lower insulin requirements during and shortly following exercise. Regardless of whether it works that way or not for an individual, there are certainly other benefits to this healthy lifestyle for both diabetics and nondiabetics.
The way diabetes is managed changes with age. Insulin production decreases because of age-related impairment of pancreatic beta cells. Additionally, insulin resistance increases because of the loss of lean tissue and the accumulation of fat, particularly intra-abdominal fat, and the decreased tissue sensitivity to insulin. Glucose tolerance progressively declines with age, leading to a high prevalence of type 2 diabetes and postchallenge hyperglycemia in the older population.<ref name="health" /> Age-related glucose intolerance in humans is often accompanied by insulin resistance, but circulating insulin levels are similar to those of younger people.<ref name="ajp">{{cite journal|author=Chang AM, Halter JB|title=Aging and insulin secretion|journal=Am. J. Physiol. Endocrinol. Metab.|volume=284|issue=1|pages=E7–12|year=2003|month=January|pmid=12485807|doi=10.1152/ajpendo.00366.2002|url=http://ajpendo.physiology.org/cgi/content/full/284/1/E7?ck=nck}}</ref> Treatment goals for older patients with diabetes vary with the individual, and take into account health status, as well as life expectancy, level of dependence, and willingness to adhere to a treatment regimen.<ref name="nidkk">{{cite web|title=Diabetes and Aging|work =Diabetes Dateline|url=http://diabetes.niddk.nih.gov/about/dateline/spri02/8.htm|year=2002|publisher=National Institute of Diabetes and Digestive and Kidney Diseases|accessdate=2007-05-14}}</ref>
=== Acute complications ===
{{Main|Diabetic ketoacidosis|nonketotic hyperosmolar coma|hypoglycemia|diabetic coma }}
; Diabetic ketoacidosis
[[Diabetic ketoacidosis]] (DKA) is an acute and dangerous complication that is always a [[medical emergency]]. Low insulin levels cause the [[liver]] to turn to fat for fuel (ie, [[ketosis]]); [[ketone bodies]] are intermediate substrates in that metabolic sequence. This is normal when periodic, but can become a serious problem if sustained. Elevated levels of ketone bodies in the blood decrease the blood's [[pH]], leading to DKA. On presentation at hospital, the patient in DKA is typically dehydrated, and breathing rapidly and deeply. Abdominal pain is common and may be severe. The [[level of consciousness]] is typically normal until late in the process, when lethargy may progress to coma. Ketoacidosis can easily become severe enough to cause [[hypotension]], [[shock (circulatory)|shock]], and death. Urine analysis will reveal significant levels of ketone bodies (which have exceeded their [[renal threshold]] blood levels to appear in the urine, often before other overt symptoms). Prompt, proper treatment usually results in full recovery, though death can result from inadequate or delayed treatment, or from complications (e.g., brain [[edema]]). DKA is always a medical emergency and requires medical attention. Ketoacidosis is much more common in type 1 diabetes than type 2.
; Hyperglycemia hyperosmolar state
[[Nonketotic hyperosmolar coma|Hyperosmolar nonketotic state]] (HNS) is an acute complication sharing many symptoms with DKA, but an entirely different origin and different treatment. A person with very high (usually considered to be above 300 mg/dl (16 mmol/L)) blood glucose levels, water is [[osmosis|osmotically]] drawn out of cells into the blood and the kidneys eventually begin to dump glucose into the urine. This results in loss of water and an increase in blood [[osmolarity]]. If fluid is not replaced (by mouth or intravenously), the osmotic effect of high glucose levels, combined with the loss of water, will eventually lead to [[dehydration]]. The body's cells become progressively dehydrated as water is taken from them and excreted. Electrolyte imbalances are also common and are always dangerous. As with DKA, urgent medical treatment is necessary, commonly beginning with fluid volume replacement. Lethargy may ultimately progress to a coma, though this is more common in type 2 diabetes than type 1.
; Hypoglycemia
[[Hypoglycemia]], or abnormally low blood glucose, is an acute complication of several diabetes treatments. It is rare otherwise, either in diabetic or non-diabetic patients. The patient may become agitated, sweaty, weak, and have many symptoms of [[Autonomic nervous system|sympathetic]] activation of the autonomic nervous system resulting in feelings akin to dread and immobilized panic. Consciousness can be altered or even lost in extreme cases, leading to coma, [[seizure]]s, or even brain damage and death. In patients with diabetes, this may be caused by several factors, such as too much or incorrectly timed insulin, too much or incorrectly timed exercise (exercise decreases insulin requirements) or not enough food (specifically glucose containing carbohydrates). The variety of interactions makes cause identification difficult in many instances.
It is more accurate to note that [[iatrogenic]] hypoglycemia is typically the result of the interplay of absolute (or relative) insulin excess and compromised glucose counterregulation in type 1 and advanced type 2 diabetes. Decrements in insulin, increments in glucagon, and, absent the latter, increments in epinephrine are the primary glucose counterregulatory factors that normally prevent or (more or less rapidly) correct hypoglycemia. In insulin-deficient diabetes (exogenous) insulin levels do not decrease as glucose levels fall, and the combination of deficient glucagon and epinephrine responses causes defective glucose counterregulation.
Furthermore, reduced sympathoadrenal responses can cause hypoglycemia unawareness. The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes posits that recent incidents of hypoglycemia causes both defective glucose counterregulation and hypoglycemia unawareness. By shifting glycemic thresholds for the sympathoadrenal (including epinephrine) and the resulting neurogenic responses to lower plasma glucose concentrations, antecedent hypoglycemia leads to a vicious cycle of recurrent hypoglycemia and further impairment of glucose counterregulation. In many cases (but not all), short-term avoidance of hypoglycemia reverses hypoglycemia unawareness in affected patients, although this is easier in theory than in clinical experience.
In most cases, hypoglycemia is treated with sugary drinks or food. In severe cases, an injection of [[glucagon]] (a hormone with effects largely opposite to those of insulin) or an [[intravenous]] infusion of [[dextrose]] is used for treatment, but usually only if the person is unconscious. In any given incident, glucagon will only work once as it uses stored liver glycogen as a glucose source; in the absence of such stores, glucagon is largely ineffective. In hospitals, intravenous dextrose is often used.
;Respiratory infections
The immune response is impaired in individuals with diabetes mellitus. Cellular studies have shown that hyperglycemia both reduces the function of immune cells and increases [[inflammation]]. The vascular effects of diabetes also tend to alter lung function, all of which leads to an increase in susceptibility to respiratory infections such as [[pneumonia]] and [[influenza]] among individuals with diabetes. Several studies also show diabetes associated with a worse disease course and slower recovery from respiratory infections.<ref>{{cite journal |author=Ahmed MS, Reid E and Khardori N|title=Respiratory infections in diabetes: Reviewing the risks and challenges |journal=Journal of Respiratory Diseases|date=June 24, 2008|url=http://www.consultantlive.com/diabetes/article/1145425/1403686}}</ref>
=== Chronic complications ===
; Vascular disease
Chronic elevation of blood glucose level leads to damage of [[blood vessel]]s ([[angiopathy]]). The [[endothelial cell]]s lining the blood vessels take in more glucose than normal, since they don't depend on insulin. They then form more surface [[glycoprotein]]s than normal, and cause the [[basement membrane]] to grow thicker and weaker. In diabetes, the resulting problems are grouped under "[[microvascular disease]]" (due to damage to small blood vessels) and "[[macrovascular disease]]" (due to damage to the [[artery|arteries]]).
However, some research challenges the theory of hyperglycemia as the cause of diabetic complications. The fact that 40% of diabetics who carefully control their blood sugar nevertheless develop neuropathy,<ref>M. Centofani, "Diabetes Complications: More than Sugar?" Science News, vol. 149, no. 26/27, Dec. 23-30, p. 421 (1995)</ref> and that some of those with good blood sugar control still develop nephropathy,<ref>{{cite journal |author=Rich SS |title=Genetics of diabetes and its complications |journal=J. Am. Soc. Nephrol. |volume=17 |issue=2 |pages=353–60 |year=2006 |month=February |pmid=16394110 |doi=10.1681/ASN.2005070770 |url=}}</ref> requires explanation. It has been discovered that the serum of diabetics with neuropathy is toxic to nerves even if its blood sugar content is normal.<ref>{{cite journal |author=Pittenger GL, Liu D, Vinik AI |title=The toxic effects of serum from patients with type 1 diabetes mellitus on mouse neuroblastoma cells: a new mechanism for development of diabetic autonomic neuropathy |journal=Diabet. Med. |volume=10 |issue=10 |pages=925–32 |year=1993 |month=December |pmid=8306588 |doi= |url=}}</ref> Recent research suggests that in type 1 diabetics, the continuing autoimmune immune disease which initially destroyed the beta cells of the pancreas may also cause retinopathy,<ref>{{cite journal |author=Kastelan S, Zjacić-Rotkvić V, Kastelan Z |title=Could diabetic retinopathy be an autoimmune disease? |journal=Med. Hypotheses |volume=68 |issue=5 |pages=1016–8 |year=2007 |pmid=17125935 |doi=10.1016/j.mehy.2006.05.073 |url=}}</ref> neuropathy,<ref>{{cite journal |author=Granberg V, Ejskjaer N, Peakman M, Sundkvist G |title=Autoantibodies to autonomic nerves associated with cardiac and peripheral autonomic neuropathy |journal=Diabetes Care |volume=28 |issue=8 |pages=1959–64 |year=2005 |month=August |pmid=16043739 |doi= |url=}}</ref> and nephropathy.<ref>{{cite journal |author=Ichinose K, Kawasaki E, Eguchi K |title=Recent advancement of understanding pathogenesis of type 1 diabetes and potential relevance to diabetic nephropathy |journal=Am. J. Nephrol. |volume=27 |issue=6 |pages=554–64 |year=2007 |pmid=17823503 |doi=10.1159/000107758 |url=}}</ref> One researcher has even suggested that retinopathy may be better treated by drugs to suppress the abnormal immune system of diabetics than by blood sugar control.<ref>Duncan Adams, "Autoimmune Destruction of Pericytes as the Cause of Diabetic Retinopathy," Clinical Ophthalmology, vol. 2, no. 2, p. 295 (2008)</ref> The familial clustering of the degree and type of diabetic complications<ref>{{cite journal |author=Monti MC, Lonsdale JT, Montomoli C, Montross R, Schlag E, Greenberg DA |title=Familial risk factors for microvascular complications and differential male-female risk in a large cohort of American families with type 1 diabetes |journal=J. Clin. Endocrinol. Metab. |volume=92 |issue=12 |pages=4650–5 |year=2007 |month=December |pmid=17878250 |doi=10.1210/jc.2007-1185 |url=}}</ref> indicates that genetics may also play a role in causing complications such as diabetic retinopathy.<ref>{{cite journal |author=Liew G, Klein R, Wong TY |title=The role of genetics in susceptibility to diabetic retinopathy |journal=Int Ophthalmol Clin |volume=49 |issue=2 |pages=35–52 |year=2009 |pmid=19349785 |doi=10.1097/IIO.0b013e31819fd5d7 |url=}}</ref> and nephropathy<ref>{{cite journal |author=Tarnow L, Groop PH, Hadjadj S, ''et al.'' |title=European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy |journal=Nephrol. Dial. Transplant. |volume=23 |issue=1 |pages=161–8 |year=2008 |month=January |pmid=17704113 |doi=10.1093/ndt/gfm501 |url=}}</ref> Non-diabetic offspring of type 2 diabetics have been found to have increased arterial stiffness and neuropathy despite normal blood glucose levels,<ref>{{cite journal |author=Foss CH, Vestbo E, Frøland A, Gjessing HJ, Mogensen CE, Damsgaard EM |title=Autonomic neuropathy in nondiabetic offspring of type 2 diabetic subjects is associated with urinary albumin excretion rate and 24-h ambulatory blood pressure: the Fredericia Study |journal=Diabetes |volume=50 |issue=3 |pages=630–6 |year=2001 |month=March |pmid=11246884 |doi= |url=}}</ref> and elevated enzyme levels associated with diabetic renal disease have been found in non-diabetic first-degree relatives of diabetics.<ref>{{cite journal |author=Ban CR, Twigg SM |title=Fibrosis in diabetes complications: pathogenic mechanisms and circulating and urinary markers |journal=Vasc Health Risk Manag |volume=4 |issue=3 |pages=575–96 |year=2008 |pmid=18827908 |pmc=2515418 |doi= |url=}}</ref><ref>P. Zaoui, et al, "Role of Metalloproteases and Inhibitors in the Occurrence and Prognosis of Diabetic Renal Lesions," Diabetes and Metabolism, vol. 26 (Supplement 4), p. 25 (2000)</ref> Even rapid tightening of blood glucose levels has been shown to worsen rather than improve diabetic complications, though it has usually been held that complications would improve over time with more normal blood sugar, provided this could be maintained.<ref>{{cite journal |author=Taubes G |title=Diabetes. Paradoxical effects of tightly controlled blood sugar |journal=Science |volume=322 |issue=5900 |pages=365–7 |year=2008 |month=October |pmid=18927369 |doi=10.1126/science.322.5900.365 |url=}}</ref> However. one study continued for 41 months found that the initial worsening of complications from improved glucose control was not followed by the expected improvement in the complications.<ref>{{cite journal |author=Brinchmann-Hansen O, Dahl-Jørgensen K, Hanssen KF, Sandvik L |title=The response of diabetic retinopathy to 41 months of multiple insulin injections, insulin pumps, and conventional insulin therapy |journal=Arch. Ophthalmol. |volume=106 |issue=9 |pages=1242–6 |year=1988 |month=September |pmid=3046587 |doi= |url=}}</ref>
[[Image:Fundus photo showing scatter laser surgery for diabetic retinopathy EDA09.JPG|thumb|Image of [[Fundus (eye)|fundus]] showing scatter [[Laser scalpel|laser surgery]] for [[diabetic retinopathy]]]]
The damage to small blood vessels leads to a [[microangiopathy]], which can cause one or more of the following:
* ''[[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 'glove and stocking' distribution starting with the feet but potentially in other nerves, later often fingers and hands. 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 amyotrophy]] is muscle weakness due to 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 in the developed world.
* ''[[Diabetic cardiomyopathy]]'', damage to the heart, leading to diastolic dysfunction and eventually [[heart failure]].
[[Macrovascular disease]] leads to cardiovascular disease, to which accelerated [[atherosclerosis]] is a contributor:
* [[Coronary artery disease]], leading to [[Angina pectoris|angina]] or [[myocardial infarction]] ("heart attack")
* [[Stroke]] (mainly the ischemic type)
* [[Peripheral artery occlusive disease|Peripheral vascular disease]], which contributes to [[intermittent claudication]] (exertion-related leg and foot pain) as well as diabetic foot.
* [[Diabetic myonecrosis]] ('muscle wasting')
Diabetic foot, often due to a combination of sensory neuropathy (numbness or insensitivity) and vascular damage, increases rates of [[skin ulcer]]s and [[infection]] and, in serious cases, [[necrosis]] and gangrene. It is why diabetics are prone to leg and foot infections and why it takes longer for them to heal from leg and foot wounds. It is the most common cause of non-traumatic adult amputation, usually of toes and or feet, in the developed world.
[[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.<!--
--><ref>{{cite journal|author=Weiss J, Sumpio B|title=Review of prevalence and outcome of vascular disease in patients with diabetes mellitus|journal=Eur J Vasc Endovasc Surg|volume=31|issue=2|pages=143–50|year=2006|pmid=16203161|doi=10.1016/j.ejvs.2005.08.015}}</ref>
Diabetic encephalopathy<ref>{{cite book|last=Aristides Veves|first=Rayaz A. Malik|title=Diabetic Neuropathy: Clinical Management (Clinical Diabetes), Second Edition|publisher=[[Humana Press]]|year=2007|pages=188–198|location=New York|isbn=1-58-829626-1}}</ref> is the increased cognitive decline and risk of [[dementia]] observed in diabetes. Various mechanisms are proposed, including alterations to the vascular supply of the brain and the interaction of insulin with the brain itself.<ref name="cspd">{{cite journal|author=Gispen WH, Biessels GJ|title=Cognition and synaptic plasticity in diabetes mellitus|journal=Trends Neurosci.|volume=23|issue=11|pages=542–9|year=2000|month=November|pmid=11074263|doi=10.1016/S0166-2236(00)01656-8 }}</ref>
== Epidemiology ==
In 2000, according to the World Health Organization, at least 171 million people worldwide suffer from diabetes, or 2.8% of the population.<ref name="Wild2004">{{cite journal|author=Wild S, Roglic G, Green A, Sicree R, King H|title=Global prevalence of diabetes: estimates for the year 2000 and projections for 2030|journal=Diabetes Care|volume=27|issue=5|pages=1047–53|year=2004|month=May|pmid=15111519|doi=10.2337/diacare.27.5.1047|url=http://care.diabetesjournals.org/cgi/content/full/27/5/1047}}</ref> Its incidence is increasing rapidly, and it is estimated that by the year 2030, this number will almost double.<ref name="Wild2004" /> Diabetes mellitus occurs throughout the world, but is more common (especially type 2) in the more developed countries. The greatest increase in prevalence is, however, expected to occur in Asia and Africa, where most patients will probably be found by 2030.<ref name="Wild2004" /> 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.<ref name="Wild2004" />
For at least 20 years, diabetes rates in North America have been increasing substantially. In 2008 there were about 24 million people with diabetes in the United States alone, from those 5.7 million people remain undiagnosed. Other 57 million people are estimated to have pre-diabetes.<ref>http://www.cdc.gov/Features/diabetesfactsheet/</ref>
The [[Centers for Disease Control]] has termed the change an [[epidemic]].<ref>{{cite web|url=http://www.cdc.gov/Diabetes/news/docs/010126.htm|title=CDC's Diabetes Program-News and Information-Press Releases-October 26 2000|work=|accessdate=2008-06-23}}</ref> 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 probably 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. The American Diabetes Association cite the 2003 assessment of the National Center for Chronic Disease Prevention and Health Promotion (Centers for Disease Control and Prevention) that 1 in 3 Americans born after 2000 will develop diabetes in their lifetime.<ref>{{cite journal|author=Narayan K, Boyle J, Thompson T, Sorensen S, Williamson D|title=Lifetime risk for diabetes mellitus in the United States|journal=JAMA|volume=290|issue=14|pages=1884–90|year=2003|pmid=14532317|doi=10.1001/jama.290.14.1884}}</ref><ref name="AA2005-Stats">{{cite web|author=American Diabetes Association|year=2005|url=http://www.diabetes.org/diabetes-statistics/prevalence.jsp|title=Total Prevalence of Diabetes & Pre-diabetes|accessdate=2006-03-17}}</ref>
According to the American Diabetes Association, approximately 18.3% (8.6 million) of Americans age 60 and older have diabetes.<ref name="dlife">{{cite web|title=Seniors and Diabetes|work =Elderly And Diabetes-Diabetes and Seniors|url=http://www.dlife.com/dLife/do/ShowContent/daily_living/seniors/|year=2006|publisher=LifeMed Media|accessdate=2007-05-14}}</ref> Diabetes mellitus prevalence increases with age, and the numbers of older persons with diabetes are expected to grow as the elderly population increases in number. The National Health and Nutrition Examination Survey (NHANES III) demonstrated that, in the population over 65 years old, 18% to 20% have diabetes, with 40% having either diabetes or its precursor form of [[impaired glucose tolerance]].<ref name="health">{{cite journal|author=Harris MI, Flegal KM, Cowie CC, ''et al.''|title=Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994|journal=Diabetes Care|volume=21|issue=4|pages=518–24|year=1998|pmid=9571335|doi=10.2337/diacare.21.4.518}}</ref>
Indigenous populations in first world countries have a higher prevalence and increasing incidence of diabetes than their corresponding non-indigenous populations. In Australia the age-standardised prevalence of self-reported diabetes in Indigenous Australians is almost 4 times that of non-indigenous Australians.<ref>{{cite web|author=Australian Institute for Health and Welfare|url=http://www.aihw.gov.au/indigenous/health/diabetes.cfm|title=Diabetes, an overview|accessdate=2008-06-23}}</ref> Preventative community health programs such as [[Sugar Man (diabetes education)]] are showing some success in tackling this problem.
== History ==
The term ''diabetes'' ({{lang-el|διαβήτης}}, ''diabētēs'') was coined by [[Aretaeus of Cappadocia]]. It was derived from the Greek verb διαβαίνειν, ''diabaínein'', itself formed from the prefix ''dia''-, "across, apart," and the verb ''bainein'', "to walk, stand." The verb ''diabeinein'' meant "to stride, walk, or stand with legs asunder"; hence, its derivative ''diabētēs'' meant "one that straddles," or specifically "a compass, siphon." The sense "siphon" gave rise to the use of ''diabētēs'' as the name for a disease involving the discharge of excessive amounts of urine. Diabetes is first recorded in English, in the form diabete, in a medical text written around 1425. In 1675, [[Thomas Willis]] added the word ''mellitus'', from the [[Latin (language)|Latin]] meaning "honey", a reference to the sweet taste of the urine. This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and Persians. In 1776, [[Matthew Dobson]] confirmed that the sweet taste was because of an excess of a kind of sugar in the urine and blood of people with diabetes.<ref>{{cite journal|last=Dobson|first=M.|coauthors=|year=1776|title=Nature of the urine in diabetes|journal=Medical Observations and Inquiries|volume=5|pages=298–310 }}</ref>
Diabetes mellitus appears to have been a death sentence in the ancient era. Hippocrates makes no mention of it, which may indicate that he felt the disease was incurable. Aretaeus did attempt to treat it but could not give a good prognosis; he commented that "life (with diabetes) is short, disgusting and painful."<ref>{{cite book|author=Medvei, Victor Cornelius|title=The history of clinical endocrinology|publisher=Parthenon Pub. Group|location=Carnforth, Lancs., U.K|year=1993|pages=23–34|isbn=1-85070-427-9 }}</ref>
[[Sushruta]] (6th century BCE) identified diabetes and classified it as ''Medhumeha''.<ref name="Dwivedi" /> He further identified it with [[obesity]] and [[sedentary]] lifestyle, advising exercises to help "cure" it.<ref name="Dwivedi">Dwivedi, Girish & Dwivedi, Shridhar (2007). [http://medind.nic.in/iae/t07/i4/iaet07i4p243.pdf ''History of Medicine: Sushruta – the Clinician – Teacher par Excellence'']. [[National Informatics Centre|National Informatics Centre (Government of India)]].</ref> The ancient [[India]]ns tested for diabetes by observing whether [[ant]]s were attracted to a person's urine, and called the ailment "sweet urine disease" (Madhumeha). The Korean, Chinese, and Japanese words for diabetes are based on the same ideographs (糖尿病) which mean "sugar urine disease".
In medieval [[History of Iran|Persia]], [[Avicenna]] (980-1037) provided a detailed account on diabetes mellitus in ''[[The Canon of Medicine]]'', "describing the abnormal appetite and the collapse of sexual functions and he documented the sweet taste of diabetic urine." Like Aretaeus before him, Avicenna recognized a primary and secondary diabetes. He also described diabetic [[gangrene]], and treated diabetes using a mixture of [[lupin]]e, [[trigonella]] ([[fenugreek]]), and [[zedoary]] seed, which produces a considerable
reduction in the excretion of sugar, a treatment which is still prescribed in modern times. Avicenna also "described diabetes insipidus very precisely for the first time", though it was later [[Johann Peter Frank]] (1745-1821) who first differentiated between diabetes mellitus and diabetes insipidus.<ref>{{citation|journal=International Journal of Endocrinology and Metabolism|year=2003|volume=1|pages=43–45 [44–5]|title=Clinical Endocrinology in the Islamic Civilization in Iran|last=Nabipour|first=I.}}</ref>
Although diabetes has been recognized since [[ancient history|antiquity]], and treatments of various efficacy have been known in various regions since the [[Middle Ages]], and in [[Snake oil|legend]] for much longer, pathogenesis of diabetes has only been understood experimentally since about 1900.<!--
--><ref name="FASEBJ2002-Patlak">{{cite journal|author=Patlak M|title=New weapons to combat an ancient disease: treating diabetes|journal=Faseb J|year=2002|pages=1853|volume=16|issue=14|url=http://www.fasebj.org/cgi/content/full/16/14/1853e|pmid=12468446|doi=10.1096/fj.02-0974bkt }}</ref>
The discovery of a role for the pancreas in diabetes is generally ascribed to [[Joseph von Mering]] and [[Oskar Minkowski]], who in 1889 found that dogs whose pancreas was removed developed all the signs and symptoms of diabetes and died shortly afterwards.<!--
--><ref>{{cite journal|author=Von Mehring J, Minkowski O.|title=Diabetes mellitus nach pankreasexstirpation|journal=Arch Exp Pathol Pharmakol|year=1890|volume=26|pages=371–387|doi=10.1007/BF01831214}}</ref>
In 1910, Sir [[Edward Albert Sharpey-Schafer]] suggested that people with diabetes were deficient in a single chemical that was normally produced by the pancreas—he proposed calling this substance ''insulin'', from the Latin ''insula'', meaning island, in reference to the insulin-producing [[islets of Langerhans]] in the pancreas.<ref name="FASEBJ2002-Patlak" />
The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was not further clarified until 1921, when Sir [[Frederick Grant Banting]] and [[Charles Herbert Best]] repeated the work of Von Mering and Minkowski, and went further to demonstrate they could reverse induced diabetes in dogs by giving them an extract from the pancreatic islets of Langerhans of healthy dogs.<!--
--><ref name="CanadMedAssocJ1922-Banting">{{cite journal|pmc=1335942|author= Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA|title=Pancreatic extracts in the treatment of diabetes mellitus|journal= Canad Med Assoc J|year=1922|pages=141–6|volume=12|pmid=1933711|issue=10|month=January|day=01}}</ref>
Banting, Best, and colleagues (especially the chemist [[James Collip|Collip]]) went on to purify the hormone insulin from bovine pancreases at the [[University of Toronto]]. This led to the availability of an effective treatment—insulin injections—and the first patient was treated in 1922. For this, Banting and laboratory director 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. Banting is honored by [[World Diabetes Day]] which is held on his birthday, November 14.
The distinction between what is now known as type 1 diabetes and type 2 diabetes was first clearly made by Sir [[Harold Percival Himsworth|Harold Percival (Harry) Himsworth]], and published in January 1936.<ref name="Lancet1936-Himsworth">{{cite journal|author= Himsworth|title=''Diabetes mellitus: its differentiation into insulin-sensitive and insulin-insensitive types|journal= Lancet|year=1936|pages=127–30|volume=i|doi=10.1016/S0140-6736(01)36134-2}}</ref>
Despite the availability of treatment, diabetes has 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]].<ref> Department of Health (Malta), 1897–1972:Annual Reports.</ref>
Other landmark discoveries include:<ref name="FASEBJ2002-Patlak" />
* Identification of the first of the [[sulfonylurea]]s in 1942
* Reintroduction of the use of [[biguanides]] for Type 2 diabetes in the late 1950s. The initial [[phenformin]] was withdrawn worldwide (in the U.S. in 1977) due to its potential for sometimes fatal lactic acidosis and [[metformin]] was first marketed in France in 1979, but not until 1994 in the US.
* The determination of the [[amino acid sequence]] of insulin (by Sir [[Frederick Sanger]], for which he received a Nobel Prize)
* The [[radioimmunoassay]] for insulin, as discovered by [[Rosalyn Yalow]] and [[Solomon Berson]] (gaining Yalow the 1977 Nobel Prize in Physiology or Medicine)<ref>{{cite journal|author=Yalow RS, Berson SA|title=Immunoassay of endogenous plasma insulin in man|journal=J. Clin. Invest.|volume=39|issue=|pages=1157–75|year=1960|pmid=13846364|doi=10.1172/JCI104130}}</ref>
* The three-dimensional structure of insulin ({{PDB|2INS}})
* Dr [[Gerald Reaven]]'s identification of the constellation of symptoms now called [[metabolic syndrome]] in 1988
* Demonstration that intensive [[Diabetes management#Glycemic control|glycemic control]] in type 1 diabetes reduces chronic side effects more as glucose levels approach 'normal' in a large longitudinal study,<ref>{{cite journal|author=The Diabetes Control And Complications Trial Research Group,|title=The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group|journal=N Engl J Med|volume=329|issue=14|pages=977–86|year=1993|pmid=8366922|doi=10.1056/NEJM199309303291401}}</ref> and also in type 2 diabetics in other large studies
* Identification of the first [[thiazolidinedione]] as an effective insulin sensitizer during the 1990s
In 1980, U.S. biotech company Genentech developed human insulin. The insulin is isolated from genetically altered bacteria (the bacteria contain the human gene for synthesizing human insulin), which produce large quantities of insulin. Scientists then purify the insulin and distribute it to pharmacies for use by diabetes patients.
== Social issues ==
The 1990 "St Vincent Declaration"<ref>{{cite book|last=Theodore H. Tulchinsky|first=Elena A. Varavikova|title=The New Public Health, Second Edition|publisher=[[Academic Press]]|year=2008|page=200|location=New York|isbn=0-12-370890-7}}</ref><ref>{{cite journal|author=Piwernetz K, Home PD, Snorgaard O, Antsiferov M, Staehr-Johansen K, Krans M.|title=Monitoring the targets of the St Vincent Declaration and the implementation of quality management in diabetes care: the DIABCARE initiative. The DIABCARE Monitoring Group of the St Vincent Declaration Steering Committee.|journal=Diabet Med.|volume=10|issue=4|pages=303–4|year=1993|pmid=8508624}}</ref> 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 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.<ref name="EO005-Dubois&Bankauskaite">{{cite journal|author= Dubois, HFW and Bankauskaite, V|title=Type 2 diabetes programmes in Europe|url= http://www.euro.who.int/Document/Obs/EuroObserver7_3.pdf|format=PDF|journal=Euro Observer|year=2005|pages=5–6|volume=7|issue=2}}</ref>
A study shows that diabetic patients with neuropathic symptoms such as [[Paresthesia|numbness]] or tingling in feet or hands are twice as likely to be [[unemployed]] as those without the symptoms.<ref name="pmid17563611">{{cite journal |author=Stewart WF, Ricci JA, Chee E, Hirsch AG, Brandenburg NA |title=Lost productive time and costs due to diabetes and diabetic neuropathic pain in the US workforce |journal=J. Occup. Environ. Med. |volume=49 |issue=6 |pages=672–9 |year=2007 |month=June |pmid=17563611 |doi=10.1097/JOM.0b013e318065b83a |url=}}</ref>
== See also ==
* [[Blood sugar]]
* [[Diabetic dermadromes]]
* [[Diabetic foot ulcer healing]]
* [[Hyperglycemia]]
* [[Glossary of terms associated with diabetes|List of terms associated with diabetes]]
* [[Diabetic hypoglycemia journal]]
== References ==
{{reflist|2}}
== External links ==
<!-- BEFORE inserting new links here you should first post it to the talk page, otherwise your edit is likely to be reverted; this section is reserved for official or authoritative resources -->
* [http://www.dmoz.org/Health/Conditions_and_Diseases/Endocrine_Disorders/Pancreas/Diabetes/ Diabetes]at the [[Open Directory Project]]
* [http://www.diabetes.org/ American Diabetes Association]
* [http://ndep.nih.gov/ National Diabetes Education Program]
{{Endocrine pathology}}
{{DEFAULTSORT:Diabetes Mellitus}}
[[Category:Diabetes]]
[[Category:Medical conditions related to obesity]]
[[Category:Nutrition]]
{{Link FA|sr}}
{{Link FA|ru}}
{{Link FA|ar}}
[[af:Suikersiekte]]
[[ar:السكري]]
[[ast:Diabetes]]
[[az:Diabet]]
[[zh-min-nan:Thn̂g-jiō-pēⁿ]]
[[bs:Diabetes mellitus]]
[[bg:Диабет]]
[[ca:Diabetis mellitus]]
[[cs:Diabetes mellitus]]
[[ckb:شەکرە]]
[[cy:Clefyd y siwgr]]
[[da:Sukkersyge]]
[[de:Diabetes mellitus]]
[[et:Suhkurtõbi]]
[[el:Διαβήτης (ασθένεια)]]
[[es:Diabetes mellitus]]
[[eo:Diabeto]]
[[eu:Diabete]]
[[fa:مرض قند]]
[[fo:Diabetes mellitus]]
[[fr:Diabète sucré]]
[[ga:Diaibéiteas]]
[[gl:Diabetes mellitus]]
[[gu:મધુપ્રમેહ]]
[[ko:당뇨병]]
[[hi:मधुमेह]]
[[hr:Diabetes mellitus]]
[[io:Diabeto]]
[[id:Diabetes mellitus]]
[[ia:Diabete]]
[[is:Sykursýki]]
[[it:Diabete mellito]]
[[he:סוכרת]]
[[kn:ಮಧುಮೇಹ]]
[[pam:Diabetes mellitus]]
[[ka:შაქრის დიაბეტი]]
[[kk:Қант диабеті]]
[[sw:Kisukari]]
[[la:Diabetes mellitus]]
[[lv:Cukura diabēts]]
[[lb:Diabetes mellitus]]
[[lt:Cukrinis diabetas]]
[[lij:Diabete Mellìo]]
[[hu:Cukorbetegség]]
[[mk:Шеќерна болест]]
[[ml:പ്രമേഹം]]
[[arz:مرض السكر]]
[[ms:Penyakit kencing manis]]
[[mn:Чихрийн шижин]]
[[nl:Diabetes mellitus]]
[[ne:मधुमेह]]
[[new:मधुमेह]]
[[ja:糖尿病]]
[[no:Diabetes mellitus]]
[[nn:Diabetes mellitus]]
[[om:Diabetes]]
[[km:ជំងឺទឹកនោមផ្អែម]]
[[pl:Cukrzyca]]
[[pt:Diabetes mellitus]]
[[ro:Diabet zaharat]]
[[qu:Misk'i unquy]]
[[ru:Сахарный диабет]]
[[sq:Diabetes mellitus]]
[[simple:Diabetes mellitus]]
[[sk:Cukrovka]]
[[sl:Sladkorna bolezen]]
[[so:Sokorow]]
[[sr:Шећерна болест]]
[[sh:Dijabetes]]
[[su:Diabétes mélitus]]
[[fi:Diabetes]]
[[sv:Diabetes]]
[[tl:Diabetes mellitus]]
[[ta:நீரிழிவு நோய்]]
[[te:మధుమేహం]]
[[th:เบาหวาน]]
[[uk:Цукровий діабет]]
[[ur:ذیابیطس]]
[[vi:Đái tháo đường]]
[[war:Diabetes mellitus]]
[[yi:צוקערקרענק]]
[[bat-smg:Sokraus diabets]]
[[zh:糖尿病]]' |
New page wikitext, after the edit (new_wikitext ) | '{{two other uses||the disease characterized by excretion of large amounts of very dilute urine|diabetes insipidus|diabetes mellitus in pets|diabetes in cats and dogs}}{{Globalize/USA}}
{{Infobox disease
| Name=Diabetes mellitus
| Image=Blue circle for diabetes.svg
| Caption=Universal blue circle symbol for diabetes.<ref>{{cite web|title=Diabetes Blue Circle Symbol|url=http://www.diabetesbluecircle.org|date=17 March 2006|publisher=International Diabetes Federation}}</ref>
| ICD10={{ICD10|E|10||e|10}}–{{ICD10|E|14||e|10}}
| ICD9={{ICD9|250}}
| MedlinePlus=001214
| EMedicineSubj=med
| EMedicineTopic=546
| EMedicine_mult={{eMedicine2|emerg|134}}
| MeshName=Diabetes
| MeshNumber=C18.452.394.750
}}
'''Diabetes mellitus''' ({{pron-en|ˌdaɪ.əˈbiːtiːz}} or {{IPA|/ˌdaɪ.əˈbiːtɨs/}}; {{IPA|/mɨˈlaɪtəs/}} or {{IPA|/ˈmɛlɨtəs/}})—often referred to simply as '''diabetes'''—is a condition in which the body either does not produce enough, or does not properly respond to, [[insulin]], a [[hormone]] produced in the [[pancreas]]. Insulin enables cells to absorb glucose in order to turn it into energy. In diabetes, the body either fails to properly respond to its own insulin, does not make enough insulin, or both. This causes glucose to accumulate in the blood, often leading to various complications.<ref name="Rother" /><ref name="diag">{{cite book|last=L M Tierney, S J McPhee|first=M A Papadakis|title=Current medical Diagnosis & Treatment. International edition|publisher=Lange Medical Books/McGraw-Hill|year=2002|pages=1203–15|location=New York|isbn=0-07-137688-7 }}</ref>
Many types of diabetes are recognized:<ref name="diag"/> The principal three are:
* ''[[Diabetes mellitus type 1|Type 1]]:'' Results from the body's failure to produce insulin. It is estimated that 5-10% of Americans who are diagnosed with diabetes have type 1 diabetes. Presently almost all persons with type 1 diabetes must take insulin injections.
* ''[[Diabetes mellitus type 2|Type 2]]:'' Results from [[Insulin resistance]], a condition in which cells fail to use insulin properly, sometimes combined with relative insulin deficiency. Most Americans who are diagnosed with diabetes have type 2 diabetes. Many people destined to develop type 2 diabetes spend many years in a state of ''[[Prediabetes|Pre-diabetes]]:'' Termed "America's largest healthcare epidemic,"<ref>Handelsman, Yehuda, MD. "A Doctor's Diagnosis: Prediabetes." ''Power of Prevention,'' Vol 1, Issue 2, 2009.</ref>{{rp|10-11|date=July 2009}}, pre-diabetes 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 diabetes. As of 2009 there are 57 million Americans who have pre-diabetes.<ref name="ADA709">{{cite web | title=All About Diabetes" | publisher=American Diabetes Association | accessdate=2009-07-01 | url=http://www.diabetes.org/about-diabetes.jsp}}</ref>
* ''[[Gestational diabetes]]:'' Pregnant women who have never had diabetes before but who have high blood sugar (glucose) levels during pregnancy are said to have gestational diabetes. Gestational diabetes affects about 4% of all pregnant women. It may precede development of type 2 (or rarely type 1).
*Many other forms of diabetes mellitus are categorized separately from these. Examples include congenital diabetes due to genetic defects of insulin secretion, cystic fibrosis-related diabetes, steroid diabetes induced by high doses of glucocorticoids, and several forms of [[MODY|monogenic diabetes]].
All forms of diabetes have been treatable since [[insulin]] became medically available in 1921, but there is no cure for the common types except a [[pancreas transplant]], although gestational diabetes usually resolves after delivery. Diabetes and its treatments can cause many complications. [[Acute (medical)|Acute]] complications including [[hypoglycemia]], [[diabetic ketoacidosis]], or [[nonketotic hyperosmolar coma]] may occur if the disease is not adequately controlled. Serious long-term complications include [[cardiovascular disease]], [[chronic renal failure]], [[diabetic retinopathy|retinal damage]], which can lead to [[blindness]], several types of [[diabetic neuropathy|nerve damage]], and microvascular damage, which may cause [[erectile dysfunction]] and poor wound healing. Poor healing of wounds, particularly of the feet, can lead to [[gangrene]], possibly requiring [[amputation]]. Adequate treatment of diabetes, as well as increased emphasis on [[blood pressure]] control and lifestyle factors such as not [[tobacco smoking|smoking]] and maintaining a healthy [[human weight|body weight]], may improve the risk profile of most of the chronic complications. In the developed world, diabetes is the most significant cause of adult blindness in the non-elderly and the leading cause of non-traumatic amputation in adults, and [[diabetic nephropathy]] is the main illness requiring [[renal dialysis]] in the United States.<ref>{{cite web|url=http://patients.uptodate.com/topic.asp?file=dialysis/15147|title=UpToDate Dialysis in diabetic nephropathy|accessdate=2007-12-07|last=Mailloux|first=Lionel|date=2007-02-13|publisher=UpToDate }}</ref>
== Classification ==
{{diabetes}}
The term ''diabetes'', without qualification, usually refers to diabetes mellitus, which roughly translates to excessive sweet urine (known as "[[glycosuria]]") but there are several rarer conditions also named diabetes. The most common of these is [[diabetes insipidus]] in which large amounts of urine are produced ([[polyuria]]), which is not sweet (insipidus meaning "without taste" in Latin); it can be caused either by [[kidney]] (nephrogenic DI) or [[pituitary gland]] (central DI) damage. It is a noninfectious disease. Among the body systems affected by Diabetes mellitus are the nervous, digestive, circulatory, endocrine and urinary systems, but all body systems are in some way affected.
The term "type 1 diabetes" has universally 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 non-insulin-dependent diabetes mellitus (NIDDM). Beyond these two types, there is no agreed-upon standard nomenclature. Various sources have defined "type 3 diabetes" as, among others, [[gestational diabetes]],<ref>{{cite web|url= http://www.diabetes.org/other-types.jsp|title=Other "types" of diabetes|publisher=[[American Diabetes Association]]|date=August 25, 2005}}</ref> insulin-resistant type 1 diabetes (or "double diabetes"), type 2 diabetes which has progressed to require injected insulin, and [[latent autoimmune diabetes]] of adults (or LADA or "[[Diabetes Type 1.5|type 1.5]]" diabetes.<ref>{{cite web|url=http://autoimmune.pathology.jhmi.edu/diseases.cfm?systemID=3&DiseaseID=23|title=Diseases: Johns Hopkins Autoimmune Disease Research Center|accessdate=2007-09-23|format=|work=}}</ref>)
=== Type 1 diabetes ===
{{Main|Diabetes mellitus type 1}}
[[Type 1 diabetes mellitus]] is characterized by loss of the insulin-producing [[beta cell]]s of the [[islets of Langerhans]] in the pancreas leading to a deficiency of insulin. This type of diabetes can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, where beta cell loss is a [[T-cell]] mediated [[autoimmunity|autoimmune]] attack.<ref name="Rother">{{cite journal|last=Rother|first=KI|year=2007|title=Diabetes Treatment — Bridging the Divide|journal=N Engl J Med|volume=356|issue=15|pages=1499–1501|url=http://content.nejm.org/cgi/content/full/356/15/1499|doi=10.1056/NEJMp078030|pmid=17429082}}</ref> There is no known preventive measure which can be taken against type 1 diabetes, which contain approximately 10% of diabetes mellitus cases in North America and Europe (though this varies by geographical location). 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 it represents a majority of the diabetes cases in children.
The principal treatment of type 1 diabetes, even in its earliest stages, is the delivery of artificial insulin via injection combined with careful monitoring of blood glucose levels using blood testing monitors. Without insulin, [[diabetic ketoacidosis]] often develops which may result in coma or death. Treatment emphasis is now also placed on lifestyle adjustments (diet and exercise) though these cannot reverse the progress of the disease. Apart from the common [[subcutaneous]] injections, it is also possible to deliver insulin by a [[insulin pump|pump]], which allows continuous infusion of insulin 24 hours a day at preset levels, and the ability to program doses (a [[Bolus (medicine)|bolus]]) of insulin as needed at meal times. An inhaled form of insulin was approved by the FDA in January 2006, although it was discontinued for business reasons in October 2007.<ref>{{cite web|url=http://www.fda.gov/bbs/topics/news/2006/NEW01304.html|title=FDA Approves First Ever Inhaled Insulin Combination Product for Treatment of Diabetes|accessdate=2007-09-09|work=}}</ref><ref>{{cite web|url=http://www.mannkindcorp.com/pressreleasetext.aspx?releaseID=1198182|title=MannKind Unveils Proposed Trade Name at Dedication of Danbury Manufacturing Facility|accessdate=2008-10-23|format=|work=}}</ref> Non-insulin treatments, such as [[monoclonal antibodies]] and [[stem-cell]] based therapies, are effective in animal models but have not yet completed clinical trials in humans.<ref>{{cite web|url=http://www.cliniclog.com/type_1_diabetes_trials.php|title=ClinicLog article on current diabetes trials.|accessdate=2008-07-23|last=Baillie|first=K|date=2008-07-05|publisher=ClinicLog.com }}</ref>
Type 1 treatment must be continued indefinitely in essentially all cases. The longest surviving Type I diabetes patient is [[Gladys Dull]], who has lived with the condition for over 83 years. Treatment need not significantly impair normal activities, if sufficient patient training, awareness, appropriate care, discipline in testing and dosing of insulin is taken. However, treatment is burdensome for patients; insulin is replaced in a non-physiological manner, and this approach is therefore far from ideal. The average glucose level for the type 1 patient should be as close to normal (80–120 mg/dl, 4–6 [[milli|m]][[Mole (unit)|mol]]/[[Litre|L]]) as is ''safely'' 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 400 mg/dl (20 mmol/L) are sometimes accompanied by discomfort and frequent urination leading to [[dehydration]]. Values above 600 mg/dl (30 mmol/L) usually require medical treatment and may lead to [[ketoacidosis]], although they are not immediately life-threatening. However, low levels of blood glucose, called [[hypoglycemia]], may lead to seizures or episodes of unconsciousness and absolutely must be treated immediately, via emergency high-glucose gel placed in the patient's mouth, intravenous administration of dextrose, or an injection of [[glucagon]].
=== Type 2 diabetes === DIABETES SUCKS!!!!!!!!!!!!!!!!!!
{{Main|Diabetes mellitus type 2}}
Type 2 diabetes mellitus is characterized differently and is due to insulin resistance or reduced insulin sensitivity, combined with relatively reduced insulin secretion which in some cases becomes absolute. The defective responsiveness of body tissues to insulin almost certainly involves the [[insulin receptor]] in cell membranes. However, the specific defects are not known. Diabetes mellitus due to a known specific defect are classified separately. Type 2 diabetes is the most common type.
In the early stage of type 2 diabetes, the predominant abnormality is reduced insulin sensitivity, characterized by elevated levels of insulin in the blood. At this stage hyperglycemia can be reversed by a variety of measures and [[Anti-diabetic drug|medications]] that improve insulin sensitivity or reduce glucose production by the [[liver]]. 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 in type 2 diabetes. [[Central obesity]] (fat concentrated around the waist in relation to abdominal organs, but not subcutaneous fat) is known to predispose individuals to insulin resistance. Abdominal fat is especially active hormonally, secreting a group of hormones called [[adipokine]]s that may possibly impair glucose tolerance. Obesity is found in approximately 55% of patients diagnosed with type 2 diabetes.<ref>{{cite journal|author=Eberhart MS, Ogden C, Engelgau M, Cadwell B, Hedley AA, Saydah SH|title=Prevalence of overweight and obesity among adults with diagnosed diabetes—United States, 1988-1994 and 1999-2002|journal=MMWR Morb. Mortal. Wkly. Rep.|volume=53|issue=45|pages=1066–8|year=2004|month=November|pmid=15549021|url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5345a2.htm}}</ref> Other factors include aging (about 20% of elderly patients in North America have diabetes) and family history (type 2 is much more common in those with close relatives who have had it). In the last decade, type 2 diabetes has increasingly begun to affect children and adolescents, probably in connection with the increased prevalence of childhood obesity seen in recent decades in some places.<ref>{{cite book|last=Arlan Rosenbloom|first=Janet H Silverstein|title=Type 2 Diabetes in Children and Adolescents: A Clinician's Guide to Diagnosis, Epidemiology, Pathogenesis, Prevention, and Treatment|publisher=American Diabetes Association,U.S.|year=2003|pages=1|isbn=978-1580401555}}</ref> Environmental exposures may contribute to recent increases in the rate of type 2 diabetes. A positive correlation has been found between the concentration in the urine of [[bisphenol A]], a constituent of polycarbonate plastic from some producers, and the incidence of type 2 diabetes.<ref>{{cite journal|author=Lang IA, Galloway TS, Scarlett A, ''et al.''|title=Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults|journal=JAMA|volume=300|issue=11|pages=1303–10|year=2008|month=September|pmid=18799442|doi=10.1001/jama.300.11.1303 }}</ref>
Type 2 diabetes may go unnoticed for years because visible symptoms are typically mild, non-existent or sporadic, and usually there are no [[Diabetic ketoacidosis|ketoacidotic episodes]]. However, severe long-term complications can result from unnoticed type 2 diabetes, including [[renal failure]] due to [[diabetic nephropathy]], vascular disease (including [[coronary artery disease]]), vision damage due to [[diabetic retinopathy]], loss of sensation or pain due to [[diabetic neuropathy]], liver damage from [[non-alcoholic steatohepatitis]] and heart failure from [[diabetic cardiomyopathy]].
Type 2 diabetes is usually first treated by increasing physical activity, decreasing [[carbohydrate]] intake, and [[weight loss|losing weight]]. 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. It is sometimes possible to achieve long-term, satisfactory glucose control with these measures alone. However, the underlying tendency to insulin resistance is not lost, and so attention to diet, exercise, and weight loss must continue. The usual next step, if necessary, is treatment with oral [[antidiabetic drug]]s. Insulin production is initially only moderately impaired in type 2 diabetes, so oral medication (often used in various combinations) can be used to improve insulin production (e.g., [[sulfonylureas]]), to regulate inappropriate release of glucose by the liver and attenuate insulin resistance to some extent (e.g., [[metformin]]), and to substantially attenuate insulin resistance (e.g., [[thiazolidinedione]]s). According to one study, overweight patients treated with metformin compared with diet alone, had [[relative risk reduction]]s of 32% for any diabetes endpoint, 42% for diabetes related death and 36% for all cause mortality and stroke.<ref>{{cite journal|author=|title=Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group|journal=Lancet|volume=352|issue=9131|pages=854–65|year=1998|pmid=9742977|doi=10.1016/S0140-6736(98)07037-8}}</ref> Oral medication may eventually fail due to further impairment of beta cell insulin secretion. At this point, insulin therapy is necessary to maintain normal or near normal glucose levels.
=== Gestational diabetes ===
{{Main|Gestational diabetes}}
Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2%–5% of all [[pregnancy|pregnancies]] and may improve or disappear after delivery. Gestational diabetes is fully treatable but requires careful medical supervision throughout the pregnancy. About 20%–50% of affected women develop type 2 diabetes later in life.
Even 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 [[Infant respiratory distress syndrome|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. [[Induction (birth)|Induction]] may be indicated with decreased placental function. A [[Caesarean section|cesarean section]] may be performed if there is marked fetal distress or an increased risk of injury associated with [[macrosomia]], such as [[shoulder dystocia]].
A 2008 study completed in the U.S. found that more American women are entering pregnancy with preexisting diabetes. In fact the rate of diabetes in expectant mothers has more than doubled in the past 6 years.<ref>{{cite journal|author=Lawrence JM, Contreras R, Chen W, Sacks DA|title=Trends in the prevalence of preexisting diabetes and gestational diabetes mellitus among a racially/ethnically diverse population of pregnant women, 1999-2005|journal=Diabetes Care|volume=31|issue=5|pages=899–904|year=2008|month=May|pmid=18223030|doi=10.2337/dc07-2345}}</ref> This is particularly problematic as diabetes raises the risk of complications during pregnancy, as well as increasing the potential that the children of diabetic mothers will also become diabetic in the future.
=== Other types ===
Most cases of diabetes mellitus fall into the two broad [[etiologic]] categories of type 1 or type 2 diabetes. However, many types of diabetes mellitus have more specific known causes, and thus fall into more specific categories. As more research is done into diabetes, many patients who were previously diagnosed as type 1 or type 2 diabetes will have their condition reclassified.
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 dominant|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.<ref name="WHO1999-DefDiagClass">{{cite web|author=[[World Health Organisation]] Department of Noncommunicable Disease Surveillance|title=Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications|year=1999|url=http://whqlibdoc.who.int/hq/1999/WHO_NCD_NCS_99.2.pdf|format=PDF}}</ref>
== Signs and symptoms ==
[[File:Main symptoms of diabetes.png|thumb|right|260px|Overview of the most significant symptoms of diabetes.]]
The classical symptoms are [[polyuria]] and [[polydipsia]] which are, respectively, frequent urination and increased thirst and consequent increased fluid intake. Symptoms may develop quite rapidly (weeks or months) in type 1 diabetes, particularly in children. However, in type 2 diabetes symptoms usually develop much more slowly and may be subtle or completely absent. Type 1 diabetes may also cause a rapid yet significant weight loss (despite normal or even increased eating) and irreducible [[mental fatigue]]. All of these symptoms except weight loss can also manifest in type 2 diabetes in patients whose diabetes is poorly controlled, although unexplained weight loss may be experienced at the onset of the disease. Final diagnosis is made by measuring the blood glucose concentration.
When the glucose concentration in the blood is raised beyond its [[renal threshold]] (about 10mmol/L, although this may be altered in certain conditions, such as pregnancy), [[reabsorption]] of glucose in the [[proximal tubule|proximal renal tubuli]] is incomplete, and part of the glucose remains in the [[urine]] ([[glycosuria]]). This increases the [[osmotic pressure]] of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production ([[polyuria]]) and increased fluid loss. Lost blood volume will be replaced osmotically from water held in body cells and other body compartments, causing [[dehydration]] and increased thirst.
Prolonged high blood glucose causes glucose absorption, which leads to changes in the shape of the lenses of the eyes, resulting in vision changes; sustained sensible glucose control usually returns the lens to its original shape. Blurred vision is a common complaint leading to a diabetes diagnosis; type 1 should always be suspected in cases of rapid vision change, whereas with type 2 change is generally more gradual, but should still be suspected.
Patients (usually with type 1 diabetes) may also initially present with diabetic ketoacidosis (DKA), an extreme state of metabolic dysregulation characterized by the smell of [[acetone]] on the patient's breath; a rapid, deep breathing known as [[Kussmaul breathing]]; [[polyuria]]; nausea; vomiting and [[abdominal pain]]; and any of many altered states of consciousness or arousal (such as hostility and mania or, equally, confusion and lethargy). In severe DKA, [[coma]] may follow, progressing to death. Diabetic ketoacidosis is a medical emergency and requires immediate hospitalization.
A rarer but equally severe possibility is [[Nonketotic hyperosmolar coma|hyperosmolar nonketotic state]], which is more common in type 2 diabetes and is mainly the result of dehydration due to loss of body water. Often, the patient has been drinking extreme amounts of sugar-containing drinks, leading to a [[positive feedback|vicious circle]] in regard to the water loss.
== 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, with some evidence pointing at [[Coxsackie B4 virus]]. There is a genetic element in individual susceptibility to some of these triggers which has been traced to particular [[Human leukocyte antigen|HLA]] [[genotype]]s (i.e., the genetic "self" identifiers relied upon by the immune system). However, even in those who have inherited the susceptibility, type 1 diabetes mellitus seems to require an environmental trigger.
There is a stronger inheritance pattern for type 2 diabetes. Those with first-degree relatives with type 2 have a much higher risk of developing type 2, increasing with the number of those relatives. [[Concordance (genetics)|Concordance]] among [[Twin#Identical twins|monozygotic twins]] is close to 100%, and about 25% of those with the disease have a family history of diabetes. Genes significantly associated with developing type 2 diabetes, include ''[[TCF7L2]]'', ''[[PPARG]]'', ''[[FTO gene|FTO]]'', ''[[KCNJ11]]'', ''[[NOTCH2]]'', ''[[WFS1]]'', ''[[CDKAL1]]'', ''[[IGF2BP2]]'', ''[[SLC30A8]]'', ''[[JAZF1]]'', and ''[[HHEX]]''.<ref>{{cite journal|author=Lyssenko V, Jonsson A, Almgren P, ''et al.''|title=Clinical risk factors, DNA variants, and the development of type 2 diabetes|journal=N. Engl. J. Med.|volume=359|issue=21|pages=2220–32|year=2008|month=November|pmid=19020324|doi=10.1056/NEJMoa0801869 }}</ref> ''KCNJ11'' ([[Inward-rectifier potassium ion channel|potassium inwardly rectifying channel]], subfamily J, member 11), encodes the islet ATP-sensitive potassium channel Kir6.2, and ''TCF7L2'' (transcription factor 7–like 2) regulates [[proglucagon]] gene expression and thus the production of [[glucagon-like peptide-1]].<ref name="Rother" /> Moreover, obesity (which is an independent risk factor for type 2 diabetes) is strongly inherited.<ref>{{cite journal|author=Walley AJ, Blakemore AI, Froguel P|title=Genetics of obesity and the prediction of risk for health|journal=Hum. Mol. Genet.|volume=15|issue=Spec No 2|pages=R124–30|year=2006|pmid=16987875|doi=10.1093/hmg/ddl215}}</ref>
[[genetic disorder|Monogenic]] forms, e.g., [[maturity onset diabetes of the young|MODY]], constitute 1-5 % of all cases.<ref>{{cite news|first=|last=|coauthors=|title=Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-onset Diabetes of the Young|date=|publisher=National Institute of Diabetes and Digestive and Kidney Diseases, NIH|url =http://www.diabetes.niddk.nih.gov/dm/pubs/mody/|work =National Diabetes Information Clearinghouse (NDIC)|accessdate=2008-08-04 }}</ref>
Various hereditary conditions may feature diabetes, for example [[myotonic dystrophy]] and [[Friedreich's ataxia]]. [[Wolfram's syndrome]] is an [[autosomal recessive]] [[neurodegenerative disorder]] that first becomes evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD.<ref name="AMN">{{cite journal|author=Barrett TG|title=Mitochondrial diabetes, DIDMOAD and other inherited diabetes syndromes|journal=Best Pract. Res. Clin. Endocrinol. Metab.|volume=15|issue=3|pages=325–43|year=2001|pmid=11554774|doi=10.1053/beem.2001.0149}}</ref>
== Pathophysiology ==
[[Image:Glucose-insulin-release.png|right|thumb|400px|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 primarily triggered by food, chiefly food containing absorbable glucose. The chief trigger is a rise in blood glucose levels after eating]]
Insulin is the principal hormone that regulates uptake of [[glucose]] from the blood into most cells (primarily muscle and fat cells, but not central nervous system cells). Therefore deficiency of insulin or the insensitivity of its [[Receptor (biochemistry)|receptors]] plays a central role in all forms of diabetes mellitus.
Most of the carbohydrates in food are converted within a few hours to the [[monosaccharide]] [[glucose]], the principal carbohydrate found in blood and used by the body as fuel. The most significant exceptions are [[fructose]], most disaccharides (except [[sucrose]] and in some people [[lactose]]), and all more complex polysaccharides, with the outstanding exception of [[starch]]. Insulin is released into the blood by beta cells (β-cells), found in the Islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the body's cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage.
Insulin is also the principal control signal for conversion of glucose to [[glycogen]] for internal storage in liver and muscle cells. Lowered glucose levels result both in the reduced release of insulin from the beta cells and in the reverse conversion of glycogen to glucose when glucose levels fall. This is mainly controlled by the hormone [[glucagon]] which acts in an opposite manner to insulin. Glucose thus recovered by the liver re-enters the bloodstream; muscle cells lack the necessary export mechanism.
Higher insulin levels increase some [[anabolism|anabolic]] ("building up") processes such as cell growth and duplication, [[protein biosynthesis|protein synthesis]], and [[lipid|fat]] storage. Insulin (or its lack) is the principal signal in converting many of the bidirectional processes of metabolism from a [[catabolism|catabolic]] to an anabolic direction, and vice versa. In particular, a low insulin level is the trigger for entering or leaving ketosis (the fat burning metabolic phase).
If the amount of insulin available is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or [[insulin resistance|resistance]]), or if the insulin itself is defective, then glucose will not be absorbed properly by those body cells that require it nor will it be stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as [[acidosis]].
== Diagnosis ==
{{Refimprove|section|date=October 2009}}
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 a quarter of people with new type 1 diabetes have developed some degree of diabetic [[ketoacidosis]](Ketoacidosis is a type of metabolic acidosis which is caused by high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids.) by the time the diabetes is recognized. The diagnosis of other types of diabetes is usually made in other ways. These include ordinary health screening; detection of hyperglycemia during other medical investigations; and secondary symptoms such as vision changes or unexplainable fatigue. Diabetes is often detected when a person suffers a problem that is frequently caused by diabetes, such as a [[myocardial infarction|heart attack]], [[stroke]], [[neuropathy]], poor wound healing or a foot ulcer, certain eye problems, certain [[fungal infection]]s, or delivering a baby with [[macrosomia]] or [[hypoglycemia]].
Diabetes mellitus is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of the following:<ref name="WHO1999-DefDiagClass" />
* Fasting plasma glucose level at or above 126 mg/dL (7.0 mmol/L).
* [[Plasma glucose]] at or above 200 mg/dL (11.1 mmol/L) two hours after a 75 g oral glucose load as in a [[glucose tolerance test]].
* Symptoms of hyperglycemia and casual plasma glucose at or above 200 mg/dL (11.1 mmol/L).
A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above-listed methods on a different day. Most physicians prefer 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.<ref>{{cite journal|author=Saydah SH, Miret M, Sung J, Varas C, Gause D, Brancati FL|journal=Diabetes Care|year=2001|volume=24|issue=8|pages=1397–402|title=Postchallenge hyperglycemia and mortality in a national sample of U.S. adults|pmid=11473076 |doi=10.2337/diacare.24.8.1397}}</ref> According to the current definition, two fasting glucose measurements above 126 mg/dL (7.0 mmol/L) is considered diagnostic for diabetes mellitus.
Patients with fasting glucose levels from 100 to 125 mg/dL (6.1 and 7.0 mmol/L) are considered to have [[impaired fasting glycemia|impaired fasting glucose]]. Patients with plasma glucose at or above 140 mg/dL or 7.8 mmol/L, but not over 200, two hours after a 75 g oral glucose load are considered to have [[impaired glucose tolerance]]. Of these two pre-diabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus as well as cardiovascular disease.<ref>{{cite web|author=Santaguida PL, Balion C, Hunt D, Morrison K, Gerstein H, Raina P, Booker L, Yazdi H|url=http://www.ahrq.gov/clinic/epcsums/impglusum.htm|title=Diagnosis, Prognosis, and Treatment of Impaired Glucose Tolerance and Impaired Fasting Glucose|work=Summary of Evidence Report/Technology Assessment, No. 128|publisher=[[Agency for Healthcare Research and Quality]]|accessdate=2008-07-20}}</ref>
While not used for diagnosis, an elevated level of glucose irreversibly bound to [[hemoglobin]] (termed [[glycated hemoglobin]] or ''HbA1c'') of 6.0% or higher (the 2003 revised U.S. standard) is considered abnormal by most labs; HbA1c is primarily used as a treatment-tracking test reflecting average blood glucose levels over the preceding 90 days (approximately) which is the average lifetime of red blood cells which contain hemoglobin in most patients. 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 6.5%.<ref>{{cite journal|last=Sniderman|first=AD|coauthors=Bhopal R, Prabhakaran D, Sarrafzadegan N, Tchernof A|title=Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis|journal=International journal of epidemiology|volume=36|issue=1|pages=220–5|year=2007|pmid=17510078|doi=10.1093/ije/dyl245}}</ref><ref>{{cite journal|author=Genuth S|title=Insights from the diabetes control and complications trial/epidemiology of diabetes interventions and complications study on the use of intensive glycemic treatment to reduce the risk of complications of type 1 diabetes|journal=Endocr Pract|issn=1530-891X|volume=12|issue=Suppl 1|pages=34–41|year =2006|month=Jan-Feb|pmid=16627378}}</ref>
== Screening ==
Diabetes screening is recommended for many people at various stages of life, and for those with any of several [[risk factors]]. The screening test varies according to circumstances and local policy, and may be a random blood glucose test, a fasting blood glucose test, a blood glucose test two hours after 75 g of glucose, or an even more formal [[glucose tolerance test]]. Many healthcare providers recommend universal screening for adults at age 40 or 50, and often periodically thereafter. Earlier screening is typically recommended for those with risk factors such as obesity, [[family history (medicine)|family history]] of diabetes, high-risk [[ethnicity]] ([[Hispanic]], [[Indigenous peoples of the Americas|Native American]], [[African diaspora|Afro-Caribbean]], [[Pacific Islander]], or [[Maori]]).<ref name="pmid17215197">{{cite journal|author=Lee CM, Huxley RR, Lam TH, Martiniuk AL, Ueshema H, Pan WH, Welborn T, Woodward M; Asia Pacific Cohort Studies Collaboration|title=Prevalence of diabetes mellitus and population attributable fractions for coronary heart disease and stroke mortality in the WHO South-East Asia and Western Pacific regions|journal=Asia Pac J Clin Nutr|volume=16|issue=1|pages=187–92|year=2007|pmid=17215197 }}</ref><ref name="pmid10889785">{{cite journal|author=Seidell JC|title=Obesity, insulin resistance and diabetes--a worldwide epidemic|journal=Br. J. Nutr.|volume=83 Suppl 1|issue=|pages=S5–8|year=2000|pmid=10889785 }}</ref>
Many medical conditions are associated with diabetes and warrant screening. A partial list includes: high blood pressure, [[dyslipidemia|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. The risk of diabetes is higher with chronic use of several medications, including high-dose [[glucocorticoid]]s, some [[chemotherapy]] agents (especially [[L-asparaginase]]), as well as some of the antipsychotics and mood stabilizers (especially [[phenothiazine]]s and some [[atypical antipsychotics]]).
People with a confirmed diagnosis of diabetes are tested routinely for complications. This includes yearly urine testing for [[microalbuminuria]] and examination of the [[retina]] of the eye for retinopathy.
== Prevention ==
Type 1 diabetes risk is known to depend upon a genetic predisposition based on [[Human leukocyte antigen|HLA]] types (particularly types DR3 and DR4), an unknown environmental trigger (suspected to be an infection, although none has proven definitive in all cases), and an uncontrolled [[autoimmune]] response that attacks the insulin producing [[beta cells]].<ref>{{cite journal|author=Daneman D|title=Type 1 diabetes|journal=Lancet|volume=367|issue=9513|pages=847–58|year=2006|pmid=16530579|doi=10.1016/S0140-6736(06)68341-4}}</ref> Some research has suggested that [[breastfeeding]] decreased the risk in later life;<ref>{{cite journal|author=Borch-Johnsen K, Joner G, Mandrup-Poulsen T, Christy M, Zachau-Christiansen B, Kastrup K, Nerup J|title=Relation between breast-feeding and incidence rates of insulin-dependent diabetes mellitus. A hypothesis|journal=Lancet|volume=2|issue=8411|pages=1083–6|year=1984|pmid=6150150|doi=10.1016/S0140-6736(84)91517-4}}</ref><ref>{{cite journal|author=Naim Shehadeh, Raanan Shamir, Moshe Berant, Amos Etzioni|title=Insulin in human milk and the prevention of type 1 diabetes|journal=Pediatric Diabetes|volume=2|issue=4|pages=175–7|year=2001|url=http://www.blackwell-synergy.com/doi/abs/10.1034/j.1399-5448.2001.20406.x?journalCode=pdi|doi=10.1034/j.1399-5448.2001.20406.x}}</ref> various other nutritional risk factors are being studied, but no firm evidence has been found.<ref>{{cite journal|author=Virtanen S, Knip M|title=Nutritional risk predictors of beta cell autoimmunity and type 1 diabetes at a young age|journal=Am J Clin Nutr|volume=78|issue=6|pages=1053–67|year=2003|pmid=14668264}}</ref>
Giving children 2000 IU of [[Vitamin D]] during their first year of life is associated with reduced risk of type 1 diabetes, though the causal relationship is obscure.<ref>{{cite journal|author=Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM|title=Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study|journal=Lancet|year=2001|pmid=11705562|volume=358|page=1500|doi=10.1016/S0140-6736(01)06580-1}}</ref>
Children with antibodies to beta cell proteins (ie at early stages of an immune reaction to them) but no overt diabetes, and treated with vitamin B-3 ([[niacin]]), had less than half the diabetes onset incidence in a 7-year time span as did the general population, and an even lower incidence relative to those with antibodies as above, but who received no vitamin B3.<ref name="pmid8961125">{{cite journal|author=Elliott RB, Pilcher CC, Fergusson DM, Stewart AW|title=A population based strategy to prevent insulin-dependent diabetes using nicotinamide|journal=J. Pediatr. Endocrinol. Metab.|volume=9|issue=5|pages=501–9|year=1996|month=Sep-Oct|pmid=8961125 }}</ref>
Type 2 diabetes risk can be reduced in many cases by making changes in diet and increasing physical activity.<ref name="pmid17098085">{{cite journal|author=Lindström J, Ilanne-Parikka P, Peltonen M, Aunola S, Eriksson J, Hemiö K, Hämäläinen H, Härkönen P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Mannelin M, Paturi M, Sundvall J, Valle T, Uusitupa M, Tuomilehto J|title=Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study|journal=Lancet|volume=368|issue=9548|pages=1673–9|year=2006|pmid=17098085|doi=10.1016/S0140-6736(06)69701-8}}</ref><ref name="Knowler">{{cite journal|author=Knowler W, Barrett-Connor E, Fowler S, Hamman R, Lachin J, Walker E, Nathan D|title=Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin|journal=N Engl J Med|volume=346|issue=6|pages=393–403|year=2002|pmid=11832527|doi=10.1056/NEJMoa012512}}</ref> The [[American Diabetes Association]] (ADA) recommends maintaining a healthy weight, getting at least 2½ hours of exercise per week (several brisk sustained walks appear sufficient), having a modest fat intake, and eating sufficient fiber (e.g., from whole grains). The ADA does not recommend [[Alcohol consumption and health|alcohol consumption]] as a preventive, but it is interesting to note that moderate alcohol intake may reduce the risk (though heavy consumption absolutely and clearly increases damage to bodily systems significantly); a similarly confused connection between low dose alcohol consumption and heart disease is termed the [[French Paradox]].
There is inadequate evidence that eating foods of low [[glycemic index]] is clinically helpful despite recommendations and suggested diets emphasizing this approach.<ref>{{cite journal|author=Bantle JP, Wylie-Rosett J, Albright AL, ''et al.''|title=Nutrition recommendations and interventions for diabetes--2006: a position statement of the American Diabetes Association|journal=Diabetes Care|volume=29|issue=9|pages=2140–57|year=2006|pmid=16936169|doi=10.2337/dc06-9914|url=http://care.diabetesjournals.org/cgi/content/full/29/9/2140}}</ref>
Diets that are very low in saturated fats reduce the risk of becoming insulin resistant and diabetic.<ref name="Barnard 2007">{{cite book|last=Barnard|first=Neal|coauthors=|year=2007|chapter=13|title=Dr. Neal Barnard's Program for Reversing Diabetes: The Scientifically Proven System for Reversing Diabetes Without Drugs|publisher=Rodale/Holtzbrinck Publishers|location=New York, NY|isbn=13 978-1-59486-528-2}}</ref><ref name="Barnard ND, Katcher HI, Jenkins DJ, Cohen J, Turner-McGrievy G 2009">{{cite journal|author=Barnard ND, Katcher HI, Jenkins DJ, Cohen J, Turner-McGrievy G|title=Vegetarian and vegan diets in type 2 diabetes management|journal=Nutr Rev|year=2009|pmid=19386029|url=http://www.ncbi.nlm.nih.gov/pubmed/19386029?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum}}</ref> Study group participants whose "physical activity level and dietary, smoking, and alcohol habits were all in the low-risk group had an 82% lower incidence of diabetes.".<ref>{{cite journal|author=Mozaffarian D, Kamineni A, Carnethon M, Djoussé L, Mukamal KJ, Siscovick D|title=Lifestyle risk factors and new-onset diabetes mellitus in older adults: the cardiovascular health study|journal=Arch Intern Med.|year=2009|pmid=19398692|url=http://www.ncbi.nlm.nih.gov/pubmed/19398692?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum}}</ref> In another study of dietary practice and incidence of diabetes, "foods rich in vegetable oils, including non-hydrogenated margarines, nuts, and seeds, should replace foods rich in saturated fats from meats and fat-rich dairy products. Consumption of partially hydrogenated fats should be minimized."<ref>{{cite journal|author=Risérus U, Willett WC, Hu FB|title=Dietary fats and prevention of type 2 diabetes|journal= Prog Lipid Res|year=2009|pmid=19032965|url=http://www.ncbi.nlm.nih.gov/pubmed/19032965?ordinalpos=20&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum}}</ref>
There are numerous studies which suggest connections between some aspects of Type II diabetes with ingestion of certain foods or with some drugs. Some studies have shown delayed progression to diabetes in predisposed patients through prophylactic use of metformin,<ref name="Knowler" /> [[rosiglitazone]],<ref>{{cite journal|author=Gerstein H, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, Hanefeld M, Hoogwerf B, Laakso M, Mohan V, Shaw J, Zinman B, Holman R|title=Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial|journal=Lancet|volume=368|issue=9541|pages=1096–105|year=2006|pmid=16997664|doi=10.1016/S0140-6736(06)69420-8}}</ref> or [[valsartan]].<ref>{{cite journal|author =Kjeldsen SE, Julius S, Mancia G, McInnes GT, Hua T, Weber MA, Coca A, Ekman S, Girerd X, Jamerson K, Larochelle P, Macdonald TM, Schmieder RE, Schork MA, Stolt P, Viskoper R, Widimsky J, Zanchetti A; for the VALUE Trial Investigators|title=Effects of valsartan compared to amlodipine on preventing type 2 diabetes in high-risk hypertensive patients: the VALUE trial|journal=J Hypertens|volume=24|issue=7|pages=1405–12|year=2006|pmid=16794491|doi=10.1097/01.hjh.0000234122.55895.5b}}</ref> In patients on [[hydroxychloroquine]] for [[rheumatoid arthritis]], incidence of diabetes was reduced by 77% though causal mechanisms are unclear.<ref>{{cite journal|author=Wasko MC, Hubert HB, Lingala VB, ''et al.''|title=Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis|journal=JAMA|volume=298|issue=2|pages=187–93|year=2007|pmid=17622600|doi=10.1001/jama.298.2.187}}</ref>
Breastfeeding may also be associated with the prevention of type 2 of the disease in mothers.<ref name="JAMA2005-Stuebe">{{cite journal|author=Stuebe AM, Rich-Edwards JW, Willett WC, Manson JE, Michels KB|title=Duration of lactation and incidence of type 2 diabetes|journal=JAMA|year=2005|pages=2601–10|volume=294|issue=20|pmid=16304074|doi=10.1001/jama.294.20.2601}}</ref> Clear evidence for these and any of many other connections between foods and supplements and diabetes is sparse to date; none, despite secondary claims for (or against), is sufficiently well established to justify as a standard clinical approach.
== Treatment and management ==
{{Main|Diabetes management}}
Diabetes mellitus is currently a [[chronic disease]] with no cure. Medical emphasis must necessarily be on managing/avoiding possible short-term as well as long-term diabetes-related problems. There is an exceptionally important role for patient education, dietetic support, sensible exercise, self monitoring of blood glucose, with the goal of keeping both short-term and long-term blood glucose levels [[Diabetes management#Glycemic control|within acceptable bounds]]. Careful control is needed to reduce the risk of long term complications. This is theoretically achievable with combinations of diet, exercise and weight loss (type 2), various oral diabetic drugs (type 2 only), and insulin use (type 1 and for type 2 not responding to oral medications, mostly those with extended duration diabetes). In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications should be undertaken to control blood pressure<ref>{{cite journal|last=Adler|first=A.I.|coauthors=Stratton, I. M.; Neil, H.A.; ''et al.''|title=Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study|pmc=27454|journal=BMJ|volume=321|issue=7258|pages=412–9|year=2000|pmid=10938049|doi=10.1136/bmj.321.7258.412}}</ref> and cholesterol by exercising more, smoking less or ideally [[smoking cessation|not at all]], consuming an appropriate [[Diabetic diet|diet]], wearing [[diabetic sock]]s, wearing diabetic shoes, and if necessary, taking any of several drugs to reduce blood pressure. Many type 1 treatments include combination use of regular or NPH insulin, and/or synthetic insulin analogs (e.g., Humalog, Novolog or Apidra) in combinations such as Lantus/Levemir and Humalog, Novolog or Apidra. Another type 1 treatment option is the use of the insulin pump (e.g., from Deltec Cozmo, Animas, Medtronic Minimed, Insulet Omnipod, or ACCU-CHEK). A [[blood lancet]] is used to pierce the skin (typically of a finger), in order to draw blood to test it for sugar levels.
In countries using a [[general practitioner]] system, such as the [[United Kingdom]], care may take place mainly outside hospitals, with hospital-based specialist care used only in case of complications, difficult blood sugar control, or research projects. In other circumstances, general practitioners and specialists share care of a patient in a team approach. [[Optometry|Optometrists]], [[podiatry|podiatrists]]/chiropodists, [[dietitian]]s, [[Physical therapy|physiotherapists]], nursing specialists (e.g., DSNs (Diabetic Specialist Nurse)), [[nurse practitioner]]s, or [[Certified diabetes educator|Certified Diabetes Educators]], may jointly provide multidisciplinary expertise. In countries where patients must provide for their own health care (e.g in the US, and in much of the undeveloped world), the impact of out-of-pocket costs of adequate diabetic care can be very high. In addition to the medications and supplies needed, patients are often advised to receive regular consultation from a physician (e.g., at least every three to six months) although research is underway to develop [[artificial intelligence]] systems which may reduce the frequency of such visits.<ref name="walker">{{cite web |last=Walker |first=Donald |title=Similarity Determination and Case Retrieval in an Intelligent Decision Support System for Diabetes Management |month=November |year=2007 |url=http://etd.ohiolink.edu/send-pdf.cgi/Walker%20Donald.pdf?acc_num=ohiou1194562654 |accessdate={{Date|2009-10-02|mdy}}}}</ref>
Oral administration of [[aloe vera]] might be a useful adjunct for lowering blood glucose in diabetic patients as well as for reducing blood lipid levels in patients with hyperlipidaemia. Ten controlled clinical trials were found to reach that conclusion in four independent literature searches. However, caveats reported in each study led the researchers to conclude that aloe vera's clinical effectiveness was not yet sufficiently defined in 1999.<ref>{{cite journal |author=Vogler BK, Ernst E |title=Aloe vera: a systematic review of its clinical effectiveness |journal=Br J Gen Pract |volume=49 |issue=447 |pages=823–8 |year=1999 |month=October |pmid=10885091 |pmc=1313538 |doi= |url=}}</ref>
[[Peer support]] links people living with diabetes. Within peer support, people with a common illness share knowledge and experience that others, including many health workers, do not have. Peer support is frequent, ongoing, accessible and flexible and can take many forms—phone calls, text messaging, group meetings, home visits, and even grocery shopping. It complements and enhances other health care services by creating the emotional, social and practical assistance necessary for managing disease and staying healthy.
== Cure ==
=== Cures for type 1 diabetes ===
{{Main|Cure for diabetes mellitus type 1}}
There is no practical cure, at this time, for type 1 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 beta cells in the Islets of Langerhans) has led to the study of several possible schemes to cure this form of diabetes mostly by replacing the pancreas or just the beta cells.<ref name="Vinik">{{cite journal|author=Vinik AI, Fishwick DT, Pittenger G|title=Advances in diabetes for the millennium: toward a cure for diabetes|journal=MedGenMed : Medscape general medicine|volume=6|issue=3 Suppl|page=12|year=2004|pmid=15647717 }}</ref> Only those type 1 diabetics who have received either a pancreas or a kidney-pancreas transplant (often when they have developed diabetic kidney disease (ie, nephropathy) and become insulin-independent) may now be considered "cured" from their diabetes. A simultaneous pancreas-kidney transplant is a promising solution, showing similar or improved survival rates over a kidney transplant alone.<ref name="Stratta">{{cite journal
| author=Stratta RJ, Alloway RR.|title=Pancreas transplantation for diabetes mellitus: a guide to recipient selection and optimum immunosuppression|journal=BioDrugs.|year=1998|pages=347–57|volume=10|issue=5|pmid=18020607
| doi=10.2165/00063030-199810050-00002 }}</ref> Still, they generally remain on long-term [[immunosuppressive drug]]s and there is a possibility that the immune system will mount a [[host versus graft]] response against the transplanted organ.<ref name="Vinik" />
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 partly due to the limited number of beta cell donors. Thus far, like any such transplant, it has provoked an immune reaction and long-term immunosuppressive drugs have been needed to protect the transplanted tissue.<ref>{{cite journal|author=Shapiro AM, Ricordi C, Hering BJ, ''et al.''|title=International trial of the Edmonton protocol for islet transplantation|journal=N. Engl. J. Med.|volume=355|issue=13|pages=1318–30|year=2006|pmid=17005949|doi=10.1056/NEJMoa061267}}</ref> An alternative technique has been proposed to place transplanted beta cells in a semi-permeable container, isolating and protecting them from the immune system. [[Stem cell research]] has also been suggested as a potential avenue for a cure since it may permit regrowth of Islet cells which are genetically part of the treated individual, thus perhaps eliminating the need for immuno-suppressants.<ref name="Vinik" />
This new method autologous nonmyeloablative hematopoietic stem cell transplantation was developed by a research team composed by Brazilian and American scientists (Dr. Julio Voltarelli, Dr. Carlos Eduardo Couri, Dr Richard Burt, and colleagues) and it was the first study to use stem cell therapy in human diabetes mellitus. This was initially tested in mice and in 2007 there was the first publication of stem cell therapy to treat this form of diabetes. Until 2009, there was 23 patients included and followed for a mean period of 29.8 months (ranging from 7 to 58 months). In the trial, severe immunosuppresion with high doses of cyclophosphamide and anti-thymocyte globulin is used with the aim of "turning off" the immunologic system", and then autologous hematopoietic stem cells are reinfused to regenerate a new one. In summary it is a kind of "immunologic reset" that blocks the autoimmune attack against residual pancreatic insulin-producing cells. Until December 2009, 12 patients remained continuously insulin-free for periods raging from 14 to 52 months and 8 patients became transiently insulin-free for periods ranging from 6 to 47 months. Of these last 8 patients, 2 became insulin-free again after the use of sitagliptin, a DPP-4 inhibitor approved only to treat type 2 diabetic patients and this is also the first study to document the use and complete insulin-independendce in humans with type 1 diabetes with this medication. In parallel with insulin suspension, indirect measures of endogenous insulin secretion revealed thate it significantly increased in the whole group of patients, regardless the need of daily exogenous insulin use. <ref>{{cite journal|author=Couri CE, Oliveira MC, Stracieri AB, ''et al.''|title=C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus|journal=JAMA|volume=301|issue=15|pages=1573–9|year=2009|month=April|pmid=19366777|doi=10.1001/jama.2009.470 }}</ref>
Microscopic or nanotechnological approaches are under investigation as well, in one proposed case with implanted stores of insulin metered out by a rapid response valve sensitive to blood glucose levels. At least two approaches have been demonstrated ''in vitro''. These are, in some sense, closed-loop insulin pumps.
=== Cures for type 2 diabetes ===
Type 2 diabetes is usually first treated by increasing physical activity, and eliminating [[saturated fat]] and reducing [[sugar]] and [[carbohydrate]] intake with a goal of [[weight loss|losing weight]]. 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. Diets that are very low in saturated fats can reverse insulin resistance.<ref name="Barnard 2007"/><ref name="Barnard ND, Katcher HI, Jenkins DJ, Cohen J, Turner-McGrievy G 2009"/>
Recently it has been shown that a type of [[gastric bypass surgery]] can normalize blood glucose levels in 80-100% of severely obese patients with diabetes. The precise causal mechanisms are being intensively researched; its results are not simply attributable to weight loss, as the improvement in blood sugars precedes any change in body mass. This approach may become a standard treatment for some people with type 2 diabetes in the relatively near future.<ref name="pmid12409659">{{cite journal|last=Rubino|first=F|coauthors=Gagner M|title=Potential of surgery for curing type 2 diabetes mellitus|journal=Ann. Surg.|volume=236|issue=5|pages=554–9|year=2002|pmid=12409659|pmc=1422611|doi=10.1097/00000658-200211000-00003}}</ref> This surgery has the additional benefit of reducing the death rate from all causes by up to 40% in severely obese people.<ref name="pmid17715409">{{cite journal|last=Adams|first=TD|coauthors=Gress RE, Smith SC, ''et al.''|title=Long-term mortality after gastric bypass surgery|journal=N. Engl. J. Med.|volume=357|issue=8|pages=753–61|year=2007|pmid=17715409|doi=10.1056/NEJMoa066603}}</ref> A small number of normal to moderately obese patients with type 2 diabetes have successfully undergone similar operations.<ref name="pmid17386401">{{cite journal|last=Cohen|first=RV|coauthors=Schiavon CA, Pinheiro JS, Correa JL, Rubino F|title=Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22-34 kg/m2: a report of 2 cases|journal=Surg Obes Relat Dis.|volume=3|issue=2|pages=195–7|year=2007|pmid=17386401|doi=10.1016/j.soard.2007.01.009}}</ref><ref name="NS">{{cite journal|last=Vasonconcelos|first=Alberto|date=2007-09-01|title= Could type 2 diabetes be reversed using surgery?
| journal=[[New Scientist]]|issue=2619|pages=11–3|url=http://www.newscientist.com/channel/health/mg19526193.100-could-type-2-diabetes-be-reversed-using-surgery.html|accessdate=2007-09-26}}</ref>
== Complications and prognosis ==
Patient education, understanding, and participation is vital since the complications of diabetes are far less common and less severe in people who have well-[[Diabetes management#Glycemic control|controlled]] blood sugar levels.<!--
--><ref>{{cite journal|last=Nathan|first=D.M.|coauthors=Cleary P.A., Backlund J.Y., ''et al.''|title=Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes|journal=N. Engl. J. Med.|volume=353|issue=25|pages=2643–53|year=2005|pmid=16371630|doi=10.1056/NEJMoa052187}}</ref><ref>{{cite journal|author=The Diabetes Control and Complications Trial Research Group|title=The effect of intensive diabetes therapy on the development and progression of neuropathy. The Diabetes Control and Complications Trial Research Group|journal=Ann. Intern. Med.|volume=122|issue=8|pages=561–8|year=1995|month=April|pmid=7887548|url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=7887548|day=15}}</ref>
Wider health problems accelerate the deleterious effects of diabetes. These include [[tobacco smoking|smoking]], [[hypercholesterolemia|elevated cholesterol]] levels, [[obesity]], [[hypertension|high blood pressure]], and lack of regular [[exercise]]. According to one study, women with high blood pressure (hypertension) were three times more likely to develop type 2 diabetes as compared with women with optimal BP after adjusting for various factors such as age, ethnicity, smoking, alcohol intake, body mass index (BMI), exercise, family history of diabetes, etc.<ref>"Women with high BP at three-fold risk of developing diabetes." TopNews.in July 1, 2009. http://www.topnews.in/women-high-bp-three-fold-risk-developing-diabetes-23341</ref> The study was conducted by researchers from the [[Brigham and Women’s Hospital]], [[Harvard Medical School]] and the [[Harvard School of Public Health]], USA, who followed over 38,000 female health professionals for ten years.
Anecdotal evidence suggests that some of those with type 2 diabetes who exercise regularly, lose weight, and eat healthy diets may be able to keep some of the disease or some of the effects of the disease in 'remission.' Certainly these tips can help prevent people predisposed to type 2 diabetes and those at pre-diabetic stages from actually developing the disorder as it helps restore insulin sensitivity. However patients should talk to their doctors about this for real expectations before undertaking it (esp. to avoid hypoglycemia or other complications); few people actually seem to go into total 'remission,' but some may find they need less of their insulin medications since the body tends to have lower insulin requirements during and shortly following exercise. Regardless of whether it works that way or not for an individual, there are certainly other benefits to this healthy lifestyle for both diabetics and nondiabetics.
The way diabetes is managed changes with age. Insulin production decreases because of age-related impairment of pancreatic beta cells. Additionally, insulin resistance increases because of the loss of lean tissue and the accumulation of fat, particularly intra-abdominal fat, and the decreased tissue sensitivity to insulin. Glucose tolerance progressively declines with age, leading to a high prevalence of type 2 diabetes and postchallenge hyperglycemia in the older population.<ref name="health" /> Age-related glucose intolerance in humans is often accompanied by insulin resistance, but circulating insulin levels are similar to those of younger people.<ref name="ajp">{{cite journal|author=Chang AM, Halter JB|title=Aging and insulin secretion|journal=Am. J. Physiol. Endocrinol. Metab.|volume=284|issue=1|pages=E7–12|year=2003|month=January|pmid=12485807|doi=10.1152/ajpendo.00366.2002|url=http://ajpendo.physiology.org/cgi/content/full/284/1/E7?ck=nck}}</ref> Treatment goals for older patients with diabetes vary with the individual, and take into account health status, as well as life expectancy, level of dependence, and willingness to adhere to a treatment regimen.<ref name="nidkk">{{cite web|title=Diabetes and Aging|work =Diabetes Dateline|url=http://diabetes.niddk.nih.gov/about/dateline/spri02/8.htm|year=2002|publisher=National Institute of Diabetes and Digestive and Kidney Diseases|accessdate=2007-05-14}}</ref>
=== Acute complications ===
{{Main|Diabetic ketoacidosis|nonketotic hyperosmolar coma|hypoglycemia|diabetic coma }}
; Diabetic ketoacidosis
[[Diabetic ketoacidosis]] (DKA) is an acute and dangerous complication that is always a [[medical emergency]]. Low insulin levels cause the [[liver]] to turn to fat for fuel (ie, [[ketosis]]); [[ketone bodies]] are intermediate substrates in that metabolic sequence. This is normal when periodic, but can become a serious problem if sustained. Elevated levels of ketone bodies in the blood decrease the blood's [[pH]], leading to DKA. On presentation at hospital, the patient in DKA is typically dehydrated, and breathing rapidly and deeply. Abdominal pain is common and may be severe. The [[level of consciousness]] is typically normal until late in the process, when lethargy may progress to coma. Ketoacidosis can easily become severe enough to cause [[hypotension]], [[shock (circulatory)|shock]], and death. Urine analysis will reveal significant levels of ketone bodies (which have exceeded their [[renal threshold]] blood levels to appear in the urine, often before other overt symptoms). Prompt, proper treatment usually results in full recovery, though death can result from inadequate or delayed treatment, or from complications (e.g., brain [[edema]]). DKA is always a medical emergency and requires medical attention. Ketoacidosis is much more common in type 1 diabetes than type 2.
; Hyperglycemia hyperosmolar state
[[Nonketotic hyperosmolar coma|Hyperosmolar nonketotic state]] (HNS) is an acute complication sharing many symptoms with DKA, but an entirely different origin and different treatment. A person with very high (usually considered to be above 300 mg/dl (16 mmol/L)) blood glucose levels, water is [[osmosis|osmotically]] drawn out of cells into the blood and the kidneys eventually begin to dump glucose into the urine. This results in loss of water and an increase in blood [[osmolarity]]. If fluid is not replaced (by mouth or intravenously), the osmotic effect of high glucose levels, combined with the loss of water, will eventually lead to [[dehydration]]. The body's cells become progressively dehydrated as water is taken from them and excreted. Electrolyte imbalances are also common and are always dangerous. As with DKA, urgent medical treatment is necessary, commonly beginning with fluid volume replacement. Lethargy may ultimately progress to a coma, though this is more common in type 2 diabetes than type 1.
; Hypoglycemia
[[Hypoglycemia]], or abnormally low blood glucose, is an acute complication of several diabetes treatments. It is rare otherwise, either in diabetic or non-diabetic patients. The patient may become agitated, sweaty, weak, and have many symptoms of [[Autonomic nervous system|sympathetic]] activation of the autonomic nervous system resulting in feelings akin to dread and immobilized panic. Consciousness can be altered or even lost in extreme cases, leading to coma, [[seizure]]s, or even brain damage and death. In patients with diabetes, this may be caused by several factors, such as too much or incorrectly timed insulin, too much or incorrectly timed exercise (exercise decreases insulin requirements) or not enough food (specifically glucose containing carbohydrates). The variety of interactions makes cause identification difficult in many instances.
It is more accurate to note that [[iatrogenic]] hypoglycemia is typically the result of the interplay of absolute (or relative) insulin excess and compromised glucose counterregulation in type 1 and advanced type 2 diabetes. Decrements in insulin, increments in glucagon, and, absent the latter, increments in epinephrine are the primary glucose counterregulatory factors that normally prevent or (more or less rapidly) correct hypoglycemia. In insulin-deficient diabetes (exogenous) insulin levels do not decrease as glucose levels fall, and the combination of deficient glucagon and epinephrine responses causes defective glucose counterregulation.
Furthermore, reduced sympathoadrenal responses can cause hypoglycemia unawareness. The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes posits that recent incidents of hypoglycemia causes both defective glucose counterregulation and hypoglycemia unawareness. By shifting glycemic thresholds for the sympathoadrenal (including epinephrine) and the resulting neurogenic responses to lower plasma glucose concentrations, antecedent hypoglycemia leads to a vicious cycle of recurrent hypoglycemia and further impairment of glucose counterregulation. In many cases (but not all), short-term avoidance of hypoglycemia reverses hypoglycemia unawareness in affected patients, although this is easier in theory than in clinical experience.
In most cases, hypoglycemia is treated with sugary drinks or food. In severe cases, an injection of [[glucagon]] (a hormone with effects largely opposite to those of insulin) or an [[intravenous]] infusion of [[dextrose]] is used for treatment, but usually only if the person is unconscious. In any given incident, glucagon will only work once as it uses stored liver glycogen as a glucose source; in the absence of such stores, glucagon is largely ineffective. In hospitals, intravenous dextrose is often used.
;Respiratory infections
The immune response is impaired in individuals with diabetes mellitus. Cellular studies have shown that hyperglycemia both reduces the function of immune cells and increases [[inflammation]]. The vascular effects of diabetes also tend to alter lung function, all of which leads to an increase in susceptibility to respiratory infections such as [[pneumonia]] and [[influenza]] among individuals with diabetes. Several studies also show diabetes associated with a worse disease course and slower recovery from respiratory infections.<ref>{{cite journal |author=Ahmed MS, Reid E and Khardori N|title=Respiratory infections in diabetes: Reviewing the risks and challenges |journal=Journal of Respiratory Diseases|date=June 24, 2008|url=http://www.consultantlive.com/diabetes/article/1145425/1403686}}</ref>
=== Chronic complications ===
; Vascular disease
Chronic elevation of blood glucose level leads to damage of [[blood vessel]]s ([[angiopathy]]). The [[endothelial cell]]s lining the blood vessels take in more glucose than normal, since they don't depend on insulin. They then form more surface [[glycoprotein]]s than normal, and cause the [[basement membrane]] to grow thicker and weaker. In diabetes, the resulting problems are grouped under "[[microvascular disease]]" (due to damage to small blood vessels) and "[[macrovascular disease]]" (due to damage to the [[artery|arteries]]).
However, some research challenges the theory of hyperglycemia as the cause of diabetic complications. The fact that 40% of diabetics who carefully control their blood sugar nevertheless develop neuropathy,<ref>M. Centofani, "Diabetes Complications: More than Sugar?" Science News, vol. 149, no. 26/27, Dec. 23-30, p. 421 (1995)</ref> and that some of those with good blood sugar control still develop nephropathy,<ref>{{cite journal |author=Rich SS |title=Genetics of diabetes and its complications |journal=J. Am. Soc. Nephrol. |volume=17 |issue=2 |pages=353–60 |year=2006 |month=February |pmid=16394110 |doi=10.1681/ASN.2005070770 |url=}}</ref> requires explanation. It has been discovered that the serum of diabetics with neuropathy is toxic to nerves even if its blood sugar content is normal.<ref>{{cite journal |author=Pittenger GL, Liu D, Vinik AI |title=The toxic effects of serum from patients with type 1 diabetes mellitus on mouse neuroblastoma cells: a new mechanism for development of diabetic autonomic neuropathy |journal=Diabet. Med. |volume=10 |issue=10 |pages=925–32 |year=1993 |month=December |pmid=8306588 |doi= |url=}}</ref> Recent research suggests that in type 1 diabetics, the continuing autoimmune immune disease which initially destroyed the beta cells of the pancreas may also cause retinopathy,<ref>{{cite journal |author=Kastelan S, Zjacić-Rotkvić V, Kastelan Z |title=Could diabetic retinopathy be an autoimmune disease? |journal=Med. Hypotheses |volume=68 |issue=5 |pages=1016–8 |year=2007 |pmid=17125935 |doi=10.1016/j.mehy.2006.05.073 |url=}}</ref> neuropathy,<ref>{{cite journal |author=Granberg V, Ejskjaer N, Peakman M, Sundkvist G |title=Autoantibodies to autonomic nerves associated with cardiac and peripheral autonomic neuropathy |journal=Diabetes Care |volume=28 |issue=8 |pages=1959–64 |year=2005 |month=August |pmid=16043739 |doi= |url=}}</ref> and nephropathy.<ref>{{cite journal |author=Ichinose K, Kawasaki E, Eguchi K |title=Recent advancement of understanding pathogenesis of type 1 diabetes and potential relevance to diabetic nephropathy |journal=Am. J. Nephrol. |volume=27 |issue=6 |pages=554–64 |year=2007 |pmid=17823503 |doi=10.1159/000107758 |url=}}</ref> One researcher has even suggested that retinopathy may be better treated by drugs to suppress the abnormal immune system of diabetics than by blood sugar control.<ref>Duncan Adams, "Autoimmune Destruction of Pericytes as the Cause of Diabetic Retinopathy," Clinical Ophthalmology, vol. 2, no. 2, p. 295 (2008)</ref> The familial clustering of the degree and type of diabetic complications<ref>{{cite journal |author=Monti MC, Lonsdale JT, Montomoli C, Montross R, Schlag E, Greenberg DA |title=Familial risk factors for microvascular complications and differential male-female risk in a large cohort of American families with type 1 diabetes |journal=J. Clin. Endocrinol. Metab. |volume=92 |issue=12 |pages=4650–5 |year=2007 |month=December |pmid=17878250 |doi=10.1210/jc.2007-1185 |url=}}</ref> indicates that genetics may also play a role in causing complications such as diabetic retinopathy.<ref>{{cite journal |author=Liew G, Klein R, Wong TY |title=The role of genetics in susceptibility to diabetic retinopathy |journal=Int Ophthalmol Clin |volume=49 |issue=2 |pages=35–52 |year=2009 |pmid=19349785 |doi=10.1097/IIO.0b013e31819fd5d7 |url=}}</ref> and nephropathy<ref>{{cite journal |author=Tarnow L, Groop PH, Hadjadj S, ''et al.'' |title=European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy |journal=Nephrol. Dial. Transplant. |volume=23 |issue=1 |pages=161–8 |year=2008 |month=January |pmid=17704113 |doi=10.1093/ndt/gfm501 |url=}}</ref> Non-diabetic offspring of type 2 diabetics have been found to have increased arterial stiffness and neuropathy despite normal blood glucose levels,<ref>{{cite journal |author=Foss CH, Vestbo E, Frøland A, Gjessing HJ, Mogensen CE, Damsgaard EM |title=Autonomic neuropathy in nondiabetic offspring of type 2 diabetic subjects is associated with urinary albumin excretion rate and 24-h ambulatory blood pressure: the Fredericia Study |journal=Diabetes |volume=50 |issue=3 |pages=630–6 |year=2001 |month=March |pmid=11246884 |doi= |url=}}</ref> and elevated enzyme levels associated with diabetic renal disease have been found in non-diabetic first-degree relatives of diabetics.<ref>{{cite journal |author=Ban CR, Twigg SM |title=Fibrosis in diabetes complications: pathogenic mechanisms and circulating and urinary markers |journal=Vasc Health Risk Manag |volume=4 |issue=3 |pages=575–96 |year=2008 |pmid=18827908 |pmc=2515418 |doi= |url=}}</ref><ref>P. Zaoui, et al, "Role of Metalloproteases and Inhibitors in the Occurrence and Prognosis of Diabetic Renal Lesions," Diabetes and Metabolism, vol. 26 (Supplement 4), p. 25 (2000)</ref> Even rapid tightening of blood glucose levels has been shown to worsen rather than improve diabetic complications, though it has usually been held that complications would improve over time with more normal blood sugar, provided this could be maintained.<ref>{{cite journal |author=Taubes G |title=Diabetes. Paradoxical effects of tightly controlled blood sugar |journal=Science |volume=322 |issue=5900 |pages=365–7 |year=2008 |month=October |pmid=18927369 |doi=10.1126/science.322.5900.365 |url=}}</ref> However. one study continued for 41 months found that the initial worsening of complications from improved glucose control was not followed by the expected improvement in the complications.<ref>{{cite journal |author=Brinchmann-Hansen O, Dahl-Jørgensen K, Hanssen KF, Sandvik L |title=The response of diabetic retinopathy to 41 months of multiple insulin injections, insulin pumps, and conventional insulin therapy |journal=Arch. Ophthalmol. |volume=106 |issue=9 |pages=1242–6 |year=1988 |month=September |pmid=3046587 |doi= |url=}}</ref>
[[Image:Fundus photo showing scatter laser surgery for diabetic retinopathy EDA09.JPG|thumb|Image of [[Fundus (eye)|fundus]] showing scatter [[Laser scalpel|laser surgery]] for [[diabetic retinopathy]]]]
The damage to small blood vessels leads to a [[microangiopathy]], which can cause one or more of the following:
* ''[[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 'glove and stocking' distribution starting with the feet but potentially in other nerves, later often fingers and hands. 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 amyotrophy]] is muscle weakness due to 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 in the developed world.
* ''[[Diabetic cardiomyopathy]]'', damage to the heart, leading to diastolic dysfunction and eventually [[heart failure]].
[[Macrovascular disease]] leads to cardiovascular disease, to which accelerated [[atherosclerosis]] is a contributor:
* [[Coronary artery disease]], leading to [[Angina pectoris|angina]] or [[myocardial infarction]] ("heart attack")
* [[Stroke]] (mainly the ischemic type)
* [[Peripheral artery occlusive disease|Peripheral vascular disease]], which contributes to [[intermittent claudication]] (exertion-related leg and foot pain) as well as diabetic foot.
* [[Diabetic myonecrosis]] ('muscle wasting')
Diabetic foot, often due to a combination of sensory neuropathy (numbness or insensitivity) and vascular damage, increases rates of [[skin ulcer]]s and [[infection]] and, in serious cases, [[necrosis]] and gangrene. It is why diabetics are prone to leg and foot infections and why it takes longer for them to heal from leg and foot wounds. It is the most common cause of non-traumatic adult amputation, usually of toes and or feet, in the developed world.
[[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.<!--
--><ref>{{cite journal|author=Weiss J, Sumpio B|title=Review of prevalence and outcome of vascular disease in patients with diabetes mellitus|journal=Eur J Vasc Endovasc Surg|volume=31|issue=2|pages=143–50|year=2006|pmid=16203161|doi=10.1016/j.ejvs.2005.08.015}}</ref>
Diabetic encephalopathy<ref>{{cite book|last=Aristides Veves|first=Rayaz A. Malik|title=Diabetic Neuropathy: Clinical Management (Clinical Diabetes), Second Edition|publisher=[[Humana Press]]|year=2007|pages=188–198|location=New York|isbn=1-58-829626-1}}</ref> is the increased cognitive decline and risk of [[dementia]] observed in diabetes. Various mechanisms are proposed, including alterations to the vascular supply of the brain and the interaction of insulin with the brain itself.<ref name="cspd">{{cite journal|author=Gispen WH, Biessels GJ|title=Cognition and synaptic plasticity in diabetes mellitus|journal=Trends Neurosci.|volume=23|issue=11|pages=542–9|year=2000|month=November|pmid=11074263|doi=10.1016/S0166-2236(00)01656-8 }}</ref>
== Epidemiology ==
In 2000, according to the World Health Organization, at least 171 million people worldwide suffer from diabetes, or 2.8% of the population.<ref name="Wild2004">{{cite journal|author=Wild S, Roglic G, Green A, Sicree R, King H|title=Global prevalence of diabetes: estimates for the year 2000 and projections for 2030|journal=Diabetes Care|volume=27|issue=5|pages=1047–53|year=2004|month=May|pmid=15111519|doi=10.2337/diacare.27.5.1047|url=http://care.diabetesjournals.org/cgi/content/full/27/5/1047}}</ref> Its incidence is increasing rapidly, and it is estimated that by the year 2030, this number will almost double.<ref name="Wild2004" /> Diabetes mellitus occurs throughout the world, but is more common (especially type 2) in the more developed countries. The greatest increase in prevalence is, however, expected to occur in Asia and Africa, where most patients will probably be found by 2030.<ref name="Wild2004" /> 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.<ref name="Wild2004" />
For at least 20 years, diabetes rates in North America have been increasing substantially. In 2008 there were about 24 million people with diabetes in the United States alone, from those 5.7 million people remain undiagnosed. Other 57 million people are estimated to have pre-diabetes.<ref>http://www.cdc.gov/Features/diabetesfactsheet/</ref>
The [[Centers for Disease Control]] has termed the change an [[epidemic]].<ref>{{cite web|url=http://www.cdc.gov/Diabetes/news/docs/010126.htm|title=CDC's Diabetes Program-News and Information-Press Releases-October 26 2000|work=|accessdate=2008-06-23}}</ref> 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 probably 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. The American Diabetes Association cite the 2003 assessment of the National Center for Chronic Disease Prevention and Health Promotion (Centers for Disease Control and Prevention) that 1 in 3 Americans born after 2000 will develop diabetes in their lifetime.<ref>{{cite journal|author=Narayan K, Boyle J, Thompson T, Sorensen S, Williamson D|title=Lifetime risk for diabetes mellitus in the United States|journal=JAMA|volume=290|issue=14|pages=1884–90|year=2003|pmid=14532317|doi=10.1001/jama.290.14.1884}}</ref><ref name="AA2005-Stats">{{cite web|author=American Diabetes Association|year=2005|url=http://www.diabetes.org/diabetes-statistics/prevalence.jsp|title=Total Prevalence of Diabetes & Pre-diabetes|accessdate=2006-03-17}}</ref>
According to the American Diabetes Association, approximately 18.3% (8.6 million) of Americans age 60 and older have diabetes.<ref name="dlife">{{cite web|title=Seniors and Diabetes|work =Elderly And Diabetes-Diabetes and Seniors|url=http://www.dlife.com/dLife/do/ShowContent/daily_living/seniors/|year=2006|publisher=LifeMed Media|accessdate=2007-05-14}}</ref> Diabetes mellitus prevalence increases with age, and the numbers of older persons with diabetes are expected to grow as the elderly population increases in number. The National Health and Nutrition Examination Survey (NHANES III) demonstrated that, in the population over 65 years old, 18% to 20% have diabetes, with 40% having either diabetes or its precursor form of [[impaired glucose tolerance]].<ref name="health">{{cite journal|author=Harris MI, Flegal KM, Cowie CC, ''et al.''|title=Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994|journal=Diabetes Care|volume=21|issue=4|pages=518–24|year=1998|pmid=9571335|doi=10.2337/diacare.21.4.518}}</ref>
Indigenous populations in first world countries have a higher prevalence and increasing incidence of diabetes than their corresponding non-indigenous populations. In Australia the age-standardised prevalence of self-reported diabetes in Indigenous Australians is almost 4 times that of non-indigenous Australians.<ref>{{cite web|author=Australian Institute for Health and Welfare|url=http://www.aihw.gov.au/indigenous/health/diabetes.cfm|title=Diabetes, an overview|accessdate=2008-06-23}}</ref> Preventative community health programs such as [[Sugar Man (diabetes education)]] are showing some success in tackling this problem.
== History ==
The term ''diabetes'' ({{lang-el|διαβήτης}}, ''diabētēs'') was coined by [[Aretaeus of Cappadocia]]. It was derived from the Greek verb διαβαίνειν, ''diabaínein'', itself formed from the prefix ''dia''-, "across, apart," and the verb ''bainein'', "to walk, stand." The verb ''diabeinein'' meant "to stride, walk, or stand with legs asunder"; hence, its derivative ''diabētēs'' meant "one that straddles," or specifically "a compass, siphon." The sense "siphon" gave rise to the use of ''diabētēs'' as the name for a disease involving the discharge of excessive amounts of urine. Diabetes is first recorded in English, in the form diabete, in a medical text written around 1425. In 1675, [[Thomas Willis]] added the word ''mellitus'', from the [[Latin (language)|Latin]] meaning "honey", a reference to the sweet taste of the urine. This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and Persians. In 1776, [[Matthew Dobson]] confirmed that the sweet taste was because of an excess of a kind of sugar in the urine and blood of people with diabetes.<ref>{{cite journal|last=Dobson|first=M.|coauthors=|year=1776|title=Nature of the urine in diabetes|journal=Medical Observations and Inquiries|volume=5|pages=298–310 }}</ref>
Diabetes mellitus appears to have been a death sentence in the ancient era. Hippocrates makes no mention of it, which may indicate that he felt the disease was incurable. Aretaeus did attempt to treat it but could not give a good prognosis; he commented that "life (with diabetes) is short, disgusting and painful."<ref>{{cite book|author=Medvei, Victor Cornelius|title=The history of clinical endocrinology|publisher=Parthenon Pub. Group|location=Carnforth, Lancs., U.K|year=1993|pages=23–34|isbn=1-85070-427-9 }}</ref>
[[Sushruta]] (6th century BCE) identified diabetes and classified it as ''Medhumeha''.<ref name="Dwivedi" /> He further identified it with [[obesity]] and [[sedentary]] lifestyle, advising exercises to help "cure" it.<ref name="Dwivedi">Dwivedi, Girish & Dwivedi, Shridhar (2007). [http://medind.nic.in/iae/t07/i4/iaet07i4p243.pdf ''History of Medicine: Sushruta – the Clinician – Teacher par Excellence'']. [[National Informatics Centre|National Informatics Centre (Government of India)]].</ref> The ancient [[India]]ns tested for diabetes by observing whether [[ant]]s were attracted to a person's urine, and called the ailment "sweet urine disease" (Madhumeha). The Korean, Chinese, and Japanese words for diabetes are based on the same ideographs (糖尿病) which mean "sugar urine disease".
In medieval [[History of Iran|Persia]], [[Avicenna]] (980-1037) provided a detailed account on diabetes mellitus in ''[[The Canon of Medicine]]'', "describing the abnormal appetite and the collapse of sexual functions and he documented the sweet taste of diabetic urine." Like Aretaeus before him, Avicenna recognized a primary and secondary diabetes. He also described diabetic [[gangrene]], and treated diabetes using a mixture of [[lupin]]e, [[trigonella]] ([[fenugreek]]), and [[zedoary]] seed, which produces a considerable
reduction in the excretion of sugar, a treatment which is still prescribed in modern times. Avicenna also "described diabetes insipidus very precisely for the first time", though it was later [[Johann Peter Frank]] (1745-1821) who first differentiated between diabetes mellitus and diabetes insipidus.<ref>{{citation|journal=International Journal of Endocrinology and Metabolism|year=2003|volume=1|pages=43–45 [44–5]|title=Clinical Endocrinology in the Islamic Civilization in Iran|last=Nabipour|first=I.}}</ref>
Although diabetes has been recognized since [[ancient history|antiquity]], and treatments of various efficacy have been known in various regions since the [[Middle Ages]], and in [[Snake oil|legend]] for much longer, pathogenesis of diabetes has only been understood experimentally since about 1900.<!--
--><ref name="FASEBJ2002-Patlak">{{cite journal|author=Patlak M|title=New weapons to combat an ancient disease: treating diabetes|journal=Faseb J|year=2002|pages=1853|volume=16|issue=14|url=http://www.fasebj.org/cgi/content/full/16/14/1853e|pmid=12468446|doi=10.1096/fj.02-0974bkt }}</ref>
The discovery of a role for the pancreas in diabetes is generally ascribed to [[Joseph von Mering]] and [[Oskar Minkowski]], who in 1889 found that dogs whose pancreas was removed developed all the signs and symptoms of diabetes and died shortly afterwards.<!--
--><ref>{{cite journal|author=Von Mehring J, Minkowski O.|title=Diabetes mellitus nach pankreasexstirpation|journal=Arch Exp Pathol Pharmakol|year=1890|volume=26|pages=371–387|doi=10.1007/BF01831214}}</ref>
In 1910, Sir [[Edward Albert Sharpey-Schafer]] suggested that people with diabetes were deficient in a single chemical that was normally produced by the pancreas—he proposed calling this substance ''insulin'', from the Latin ''insula'', meaning island, in reference to the insulin-producing [[islets of Langerhans]] in the pancreas.<ref name="FASEBJ2002-Patlak" />
The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was not further clarified until 1921, when Sir [[Frederick Grant Banting]] and [[Charles Herbert Best]] repeated the work of Von Mering and Minkowski, and went further to demonstrate they could reverse induced diabetes in dogs by giving them an extract from the pancreatic islets of Langerhans of healthy dogs.<!--
--><ref name="CanadMedAssocJ1922-Banting">{{cite journal|pmc=1335942|author= Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA|title=Pancreatic extracts in the treatment of diabetes mellitus|journal= Canad Med Assoc J|year=1922|pages=141–6|volume=12|pmid=1933711|issue=10|month=January|day=01}}</ref>
Banting, Best, and colleagues (especially the chemist [[James Collip|Collip]]) went on to purify the hormone insulin from bovine pancreases at the [[University of Toronto]]. This led to the availability of an effective treatment—insulin injections—and the first patient was treated in 1922. For this, Banting and laboratory director 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. Banting is honored by [[World Diabetes Day]] which is held on his birthday, November 14.
The distinction between what is now known as type 1 diabetes and type 2 diabetes was first clearly made by Sir [[Harold Percival Himsworth|Harold Percival (Harry) Himsworth]], and published in January 1936.<ref name="Lancet1936-Himsworth">{{cite journal|author= Himsworth|title=''Diabetes mellitus: its differentiation into insulin-sensitive and insulin-insensitive types|journal= Lancet|year=1936|pages=127–30|volume=i|doi=10.1016/S0140-6736(01)36134-2}}</ref>
Despite the availability of treatment, diabetes has 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]].<ref> Department of Health (Malta), 1897–1972:Annual Reports.</ref>
Other landmark discoveries include:<ref name="FASEBJ2002-Patlak" />
* Identification of the first of the [[sulfonylurea]]s in 1942
* Reintroduction of the use of [[biguanides]] for Type 2 diabetes in the late 1950s. The initial [[phenformin]] was withdrawn worldwide (in the U.S. in 1977) due to its potential for sometimes fatal lactic acidosis and [[metformin]] was first marketed in France in 1979, but not until 1994 in the US.
* The determination of the [[amino acid sequence]] of insulin (by Sir [[Frederick Sanger]], for which he received a Nobel Prize)
* The [[radioimmunoassay]] for insulin, as discovered by [[Rosalyn Yalow]] and [[Solomon Berson]] (gaining Yalow the 1977 Nobel Prize in Physiology or Medicine)<ref>{{cite journal|author=Yalow RS, Berson SA|title=Immunoassay of endogenous plasma insulin in man|journal=J. Clin. Invest.|volume=39|issue=|pages=1157–75|year=1960|pmid=13846364|doi=10.1172/JCI104130}}</ref>
* The three-dimensional structure of insulin ({{PDB|2INS}})
* Dr [[Gerald Reaven]]'s identification of the constellation of symptoms now called [[metabolic syndrome]] in 1988
* Demonstration that intensive [[Diabetes management#Glycemic control|glycemic control]] in type 1 diabetes reduces chronic side effects more as glucose levels approach 'normal' in a large longitudinal study,<ref>{{cite journal|author=The Diabetes Control And Complications Trial Research Group,|title=The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group|journal=N Engl J Med|volume=329|issue=14|pages=977–86|year=1993|pmid=8366922|doi=10.1056/NEJM199309303291401}}</ref> and also in type 2 diabetics in other large studies
* Identification of the first [[thiazolidinedione]] as an effective insulin sensitizer during the 1990s
In 1980, U.S. biotech company Genentech developed human insulin. The insulin is isolated from genetically altered bacteria (the bacteria contain the human gene for synthesizing human insulin), which produce large quantities of insulin. Scientists then purify the insulin and distribute it to pharmacies for use by diabetes patients.
== Social issues ==
The 1990 "St Vincent Declaration"<ref>{{cite book|last=Theodore H. Tulchinsky|first=Elena A. Varavikova|title=The New Public Health, Second Edition|publisher=[[Academic Press]]|year=2008|page=200|location=New York|isbn=0-12-370890-7}}</ref><ref>{{cite journal|author=Piwernetz K, Home PD, Snorgaard O, Antsiferov M, Staehr-Johansen K, Krans M.|title=Monitoring the targets of the St Vincent Declaration and the implementation of quality management in diabetes care: the DIABCARE initiative. The DIABCARE Monitoring Group of the St Vincent Declaration Steering Committee.|journal=Diabet Med.|volume=10|issue=4|pages=303–4|year=1993|pmid=8508624}}</ref> 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 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.<ref name="EO005-Dubois&Bankauskaite">{{cite journal|author= Dubois, HFW and Bankauskaite, V|title=Type 2 diabetes programmes in Europe|url= http://www.euro.who.int/Document/Obs/EuroObserver7_3.pdf|format=PDF|journal=Euro Observer|year=2005|pages=5–6|volume=7|issue=2}}</ref>
A study shows that diabetic patients with neuropathic symptoms such as [[Paresthesia|numbness]] or tingling in feet or hands are twice as likely to be [[unemployed]] as those without the symptoms.<ref name="pmid17563611">{{cite journal |author=Stewart WF, Ricci JA, Chee E, Hirsch AG, Brandenburg NA |title=Lost productive time and costs due to diabetes and diabetic neuropathic pain in the US workforce |journal=J. Occup. Environ. Med. |volume=49 |issue=6 |pages=672–9 |year=2007 |month=June |pmid=17563611 |doi=10.1097/JOM.0b013e318065b83a |url=}}</ref>
== See also ==
* [[Blood sugar]]
* [[Diabetic dermadromes]]
* [[Diabetic foot ulcer healing]]
* [[Hyperglycemia]]
* [[Glossary of terms associated with diabetes|List of terms associated with diabetes]]
* [[Diabetic hypoglycemia journal]]
== References ==
{{reflist|2}}
== External links ==
<!-- BEFORE inserting new links here you should first post it to the talk page, otherwise your edit is likely to be reverted; this section is reserved for official or authoritative resources -->
* [http://www.dmoz.org/Health/Conditions_and_Diseases/Endocrine_Disorders/Pancreas/Diabetes/ Diabetes]at the [[Open Directory Project]]
* [http://www.diabetes.org/ American Diabetes Association]
* [http://ndep.nih.gov/ National Diabetes Education Program]
{{Endocrine pathology}}
{{DEFAULTSORT:Diabetes Mellitus}}
[[Category:Diabetes]]
[[Category:Medical conditions related to obesity]]
[[Category:Nutrition]]
{{Link FA|sr}}
{{Link FA|ru}}
{{Link FA|ar}}
[[af:Suikersiekte]]
[[ar:السكري]]
[[ast:Diabetes]]
[[az:Diabet]]
[[zh-min-nan:Thn̂g-jiō-pēⁿ]]
[[bs:Diabetes mellitus]]
[[bg:Диабет]]
[[ca:Diabetis mellitus]]
[[cs:Diabetes mellitus]]
[[ckb:شەکرە]]
[[cy:Clefyd y siwgr]]
[[da:Sukkersyge]]
[[de:Diabetes mellitus]]
[[et:Suhkurtõbi]]
[[el:Διαβήτης (ασθένεια)]]
[[es:Diabetes mellitus]]
[[eo:Diabeto]]
[[eu:Diabete]]
[[fa:مرض قند]]
[[fo:Diabetes mellitus]]
[[fr:Diabète sucré]]
[[ga:Diaibéiteas]]
[[gl:Diabetes mellitus]]
[[gu:મધુપ્રમેહ]]
[[ko:당뇨병]]
[[hi:मधुमेह]]
[[hr:Diabetes mellitus]]
[[io:Diabeto]]
[[id:Diabetes mellitus]]
[[ia:Diabete]]
[[is:Sykursýki]]
[[it:Diabete mellito]]
[[he:סוכרת]]
[[kn:ಮಧುಮೇಹ]]
[[pam:Diabetes mellitus]]
[[ka:შაქრის დიაბეტი]]
[[kk:Қант диабеті]]
[[sw:Kisukari]]
[[la:Diabetes mellitus]]
[[lv:Cukura diabēts]]
[[lb:Diabetes mellitus]]
[[lt:Cukrinis diabetas]]
[[lij:Diabete Mellìo]]
[[hu:Cukorbetegség]]
[[mk:Шеќерна болест]]
[[ml:പ്രമേഹം]]
[[arz:مرض السكر]]
[[ms:Penyakit kencing manis]]
[[mn:Чихрийн шижин]]
[[nl:Diabetes mellitus]]
[[ne:मधुमेह]]
[[new:मधुमेह]]
[[ja:糖尿病]]
[[no:Diabetes mellitus]]
[[nn:Diabetes mellitus]]
[[om:Diabetes]]
[[km:ជំងឺទឹកនោមផ្អែម]]
[[pl:Cukrzyca]]
[[pt:Diabetes mellitus]]
[[ro:Diabet zaharat]]
[[qu:Misk'i unquy]]
[[ru:Сахарный диабет]]
[[sq:Diabetes mellitus]]
[[simple:Diabetes mellitus]]
[[sk:Cukrovka]]
[[sl:Sladkorna bolezen]]
[[so:Sokorow]]
[[sr:Шећерна болест]]
[[sh:Dijabetes]]
[[su:Diabétes mélitus]]
[[fi:Diabetes]]
[[sv:Diabetes]]
[[tl:Diabetes mellitus]]
[[ta:நீரிழிவு நோய்]]
[[te:మధుమేహం]]
[[th:เบาหวาน]]
[[uk:Цукровий діабет]]
[[ur:ذیابیطس]]
[[vi:Đái tháo đường]]
[[war:Diabetes mellitus]]
[[yi:צוקערקרענק]]
[[bat-smg:Sokraus diabets]]
[[zh:糖尿病]]' |