Diabetes mellitus type 1

Main article: Diabetes mellitus
Diabetes mellitus type 1
Classification and external resources

Universal blue circle symbol for diabetes.[1]
ICD-10 E10
ICD-9 250.x1, 250.x3
OMIM 222100
DiseasesDB 3649
MedlinePlus 000305
eMedicine med/546
MeSH D003922

Diabetes mellitus type 1 (Type 1 diabetes, IDDM, or juvenile diabetes) is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas.[2] The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms of polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss result.[3]

Type 1 diabetes is fatal unless treated with insulin. Injection is the most common method of administering insulin; insulin pumps and inhaled insulin have been available at various times. Pancreas transplants have been used to treat type 1 diabetes; however, this procedure is currently still at the experimental trial stage.[4]

Most people who develop type 1 are otherwise healthy.[5] Although the cause of type 1 diabetes is still not fully understood it is believed to be of immunological origin. There is a growing body of evidence that diet may play a role in the development of type 1 diabetes, through influencing gut flora, intestinal permeability, and immune function in the gut; wheat in particular has been shown to have a connection to the development of type 1 diabetes, although the relationship is poorly understood.[6] Type 1 can be distinguished from type 2 diabetes via a C-peptide assay, which measures endogenous insulin production.

Type 1 treatment must be continued indefinitely in all cases. 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 many people. Complications may be associated with both low blood sugar and high blood sugar. Low blood sugar may lead to seizures or episodes of unconsciousness and requires emergency treatment. High blood sugar may lead to increased tiredness and can also result in long term damage to other organs such as eyes and joints.

Contents

Signs and symptoms

The classical symptoms of type 1 diabetes include: polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), tiredness, and weight loss.[3]

Cause

Environment

Environmental factors can strongly influence expression of type 1. A study showed that for identical twins, when one twin had type 1 diabetes, the other twin only had type 1 30%–50% of the time. Despite having the exact same genome, one twin had the disease, where the other did not; this suggests that environmental factors, in addition to genetic factors, can influence disease prevalence.[7]

Genetics

Type 1 diabetes is a polygenic disease, meaning many different genes contribute to its expression. Depending on locus or combination of loci, it can be dominant, recessive, or somewhere in between. The strongest gene, IDDM1, is located in the MHC Class II region on chromosome 6, at staining region 6p21. This is believed to be responsible for the histocompatibility disorder characteristic of type 1: Insulin-producing pancreas cells (beta cells) display improper antigens to T cells.

Pathophysiology

The cause of type 1 diabetes is not fully understood. One theory, discussed by DeLisa Fairweather & Noel R. Rose, among others,[8] proposes that type 1 diabetes is a virally triggered autoimmune response in which the immune system attacks virus infected cells along with the beta cells in the pancreas. The Coxsackie virus family or German measles is implicated, although the evidence is inconclusive. In type 1, pancreatic beta cells in the Islets of Langerhans are destroyed decreasing endogenous insulin production. This distinguishes type 1's origin from type 2 DM. The type of diabetes a patient has is determined only by the cause—fundamentally by whether the patient is insulin resistant (type 2) or insulin deficient without insulin resistance (type 1).

This vulnerability is not shared by everyone, for not everyone infected by the suspected organisms develops type 1 diabetes. This has suggested presence of a genetic vulnerability[9] and there is indeed an observed inherited tendency to develop type 1. It has been traced to particular HLA genotypes, though the connection between them and the triggering of an auto-immune reaction is still poorly understood.

Short breast-feeding period and short attendance to day care is associated with the risk of type 1 diabetes in Czech children.[10]

Some researchers believe that the autoimmune response is influenced by antibodies against cow's milk proteins.[11] No connection has been established between autoantibodies, antibodies to cow's milk proteins, and type 1 diabetes. A subtype of type 1 (identifiable by the presence of antibodies against beta cells) typically develops slowly and so is often confused with type 2. In addition, a small proportion of type 2 cases manifest a genetic form of the disease called maturity onset diabetes of the young (MODY).

Vitamin D in doses of 2000 IU per day given during the first year of a child's life has been connected in one study in Northern Finland (where intrinsic production of Vitamin D is low due to low natural light levels) with an 80% reduction in the risk of getting type 1 diabetes later in life. The causal connection, if any, is obscure.

Type 1 diabetes was previously known as juvenile diabetes because it is one of the most frequent chronic diseases in children; however, the majority of new-onset type 1 diabetes is seen in adults. Scientific studies that use antibody testing (glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), and insulinoma-associated autoantibodies (IA-2)) to distinguish between type 1 and type 2 diabetes demonstrate that most new-onset type 1 diabetes is seen in adults. A 2008 book, Type 1 Diabetes in Adults: Principles and Practice, says that adult-onset type 1 autoimmune diabetes is two to three times more common than classic childhood-onset autoimmune diabetes.[12] In type 1 diabetes, the body does not produce insulin. Insulin is a hormone that is needed to maintain normal blood glucose levels (3.6 to 5.8 mM glucose) within the body, when spikes in blood glucose concentration occurs. One mechanism by which insulin does such is by causing the liver to take up glucose molecules and convert them to glycogen for storage in the liver.

Some chemicals and drugs preferentially destroy pancreatic cells. Pyrinuron (Vacor, N-3-pyridylmethyl-N'-p-nitrophenyl urea), a rodenticide introduced in the United States in 1976, selectively destroys pancreatic beta cells, resulting in type 1 diabetes after accidental or intentional ingestion. Vacor was withdrawn from the U.S. market in 1979, but is still used in some countries. Zanosar is the trade name for streptozotocin, an antibiotic and antineoplastic agent used in chemotherapy for pancreatic cancer; it also kills beta cells, resulting in loss of insulin production. Other pancreatic problems, including trauma, pancreatitis or tumors (either malignant or benign), can also lead to loss of insulin production.

The exact cause(s) of type 1 diabetes are not yet fully understood, and research on those mentioned, and others, continues.

Diagnosis

See also: Glycosylated hemoglobin and Glucose tolerance test
2006 WHO Diabetes criteria[13]  edit
Condition 2 hour glucose Fasting glucose
mmol/l(mg/dl) mmol/l(mg/dl)
Normal <7.8 (<140) <6.1 (<110)
Impaired fasting glycaemia <7.8 (<140) ≥ 6.1(≥110) & <7.0(<126)
Impaired glucose tolerance ≥7.8 (≥140) <7.0 (<126)
Diabetes mellitus ≥11.1 (≥200) ≥7.0 (≥126)

Diabetes mellitus is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of the following:[14]

About a quarter of people with new type 1 diabetes have developed some degree of diabetic ketoacidosis (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 heart attack, stroke, neuropathy, poor wound healing or a foot ulcer, certain eye problems, certain fungal infections, or delivering a baby with macrosomia or hypoglycemia.

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.[16] 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 (5.6 to 6.9 mmol/L) are considered to have impaired fasting glucose. Patients with plasma glucose at or above 140 mg/dL (7.8 mmol/L), but not over 200 mg/dL (11.1 mmol/L), 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.[17]

Prevention

Type 1 diabetes risk is known to depend upon a genetic predisposition based on 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.[18] Some research has suggested that breastfeeding decreased the risk in later life;[19][20] various other nutritional risk factors are being studied, but no firm evidence has been found.[21] 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.[22]

Children with antibodies to beta cell proteins (i.e. at early stages of an immune reaction to them) but no overt diabetes, and treated with vitamin B3 (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.[23]

Management

Type 1 is treated with insulin replacement therapy—usually by insulin injection or insulin pump, along with attention to dietary management, typically including carbohydrate tracking, and careful monitoring of blood glucose levels using glucose meters. Today the most common insulins are biosynthetic products produced using genetic recombination techniques; formerly, cattle or pig insulins were used, and even sometimes insulin from fish[24]. Major global suppliers include Eli Lilly and Company, Novo Nordisk, and Sanofi-Aventis. A more recent trend, from several suppliers, is insulin analogs which are slightly modified insulins which have different onset of action times or duration of action times.

Untreated type 1 diabetes commonly leads to coma, often from diabetic ketoacidosis, which is fatal if untreated. Continuous glucose monitors have been developed and marketed which can alert patients to the presence of dangerously high or low blood sugar levels, but technical limitations have limited the impact these devices have had on clinical practice so far.

In more extreme cases, a pancreas transplant can restore proper glucose regulation. However, the surgery and accompanying immunosuppression required is considered by many physicians to be more dangerous than continued insulin replacement therapy, and is therefore often used only as a last resort (such as when a kidney must also be transplanted, or in cases where the patient's blood glucose levels are extremely volatile). Experimental replacement of beta cells (by transplant or from stem cells) is being investigated in several research programs. Thus far, beta cell replacement has only been performed on patients over age 18, and with tantalizing successes amidst nearly universal failure.

Pancreas transplantation

Pancreas transplants are generally performed together with or some time after a kidney transplant. One reason for this is that introducing a new kidney requires taking immunosuppressive drugs such as cyclosporin. Nevertheless this allows the introduction of a new, functioning pancreas to a patient with diabetes without any additional immunosuppressive therapy. However, pancreas transplants alone can be wise in patients with extremely labile type 1 diabetes mellitus.[25]

Islet cell transplantation

Islet cell transplantation is expected to be less invasive than a pancreas transplant which is currently the most commonly used approach in humans.

In one variant of this procedure, islet cells are injected into the patient's liver, where they take up residence and begin to produce insulin. The liver is expected to be the most reasonable choice because it is more accessible than the pancreas, and islet cells seem to produce insulin well in that environment. The patient's body, however, will treat the new cells just as it would any other introduction of foreign tissue, unless a method is developed to produce them from the patient's own stem cells or there is an identical twin available who can donate stem cells. The immune system will attack the cells as it would a bacterial infection or a skin graft. Thus, patients now also need to undergo treatment involving immunosuppressants, which reduce immune system activity.

Recent studies have shown that islet cell transplants have progressed to the point that 58% of the patients in one study were insulin independent one year after islet cell transplant.[26] Ideally, it would be best to use islet cells which will not provoke this immune reaction. Scientists in New Zealand with Living Cell Technologies are currently in human trials with Diabecell, placing pig islets within a protective capsule derived of seaweed which enables insulin to flow out and nutrients to flow in while protecting the islets from immune system attack via white blood cells.

Prognosis

Complications of poorly-managed type 1 diabetes mellitus may include cardiovascular disease, diabetic neuropathy, diabetic retinopathy among others. Overweight or obese people having T1DM are especially likely to have these problems if substandard diet is involved or the cholesterol or blood pressure is not well-controlled.[27] There is some evidence that cardiovascular disease[28] as well as neuropathy[29] may, in fact, have an autoimmune basis as well.

Epidemiology

It is estimated that about 5%–10% of North American diabetes patients have type 1.[30] The fraction of type 1 in other parts of the world differs; this is likely due to both differences in the rate of type 1 and differences in the rate of other types, most prominently type 2. Most of this difference is not currently understood. Variable criteria for categorizing diabetes types may play a part. The longest surviving Type I diabetes patient is Gladys Dull, who has lived with the condition for over 83 years.

Research

This section is an incomplete list of mainly commercial companies but also other entities, namely governmental institutions and individual persons, actively involved in research towards finding a cure to diabetes type 1. It does not list research funds, hospitals in which research is undertaken, etc., but only the industrious, actual developers of such products.

Entities are listed alphabetically along with their status of research in that field, so that also entities which ceased research into finding a cure to diabetes type 1 may be listed.

Foundations

The Juvenile Diabetes Research Foundation (JDRF) is the major charitable organization in the USA, Canada and Australia devoted to type 1 diabetes research. JDRF's mission is to cure type 1 diabetes and its complications through the support of research. Since its founding in 1970, JDRF has contributed more than $1.3 billion to diabetes research, including more than $156 million in FY 2008. In FY 2008, the Foundation funded 1,000 centers, grants and fellowships in 22 countries. In November 2008 JDRF launched an online social network for people with type 1 diabetes: Juvenation.

The International Diabetes Federation is a worldwide alliance of over 160 countries to address diabetes research and treatment. The American Diabetes Association funds some work on type 1 but devotes much of its resources to type 2 diabetes due to the increasing prevalence of the type 2 version. Diabetes Australia is involved in promoting research and education in Australia on both type 1 and type 2 diabetes, however, like the American Diabetes Association, spends most of its time and resources on type 2. The Canadian Diabetes Association is involved in educating, researching, and sustaining type 1 diabetes patients in Canada. Pacific Northwest Diabetes Research Institute conducts clinical and basic research on type 1 and type 2 diabetes.

There are a number of patient-support focused foundations that have grown to prominence since 2007. Diabetic Rockstar Inc[31] is a both an online support community and non-profit focused on helping newly diagnosed, uninsured and financially struggling diabetics. Diabetes Sisters is also an online support group for women that uses offline interaction to help women of all ages.

Prevention

"Immunization" approach

If a biochemical mechanism can be found that prevents the immune system from attacking beta cells, it may be administered to prevent commencement of diabetes type 1. Several groups are trying to achieve this by causing the activation state of the immune system to change from Th1 state (“attack” by killer T Cells) to Th2 state (development of new antibodies). This Th1-Th2 shift occurs via a change in the type of cytokine signaling molecules being released by regulatory T-cells. Instead of pro-inflammatory cytokines, the regulatory T-cells begin to release cytokines that inhibit inflammation.[32] This phenomenon is commonly known as "acquired immune tolerance".

DiaPep277

A substance designed to cause lymphocyte cells to cease attacking beta cells, DiaPep277 is a peptide fragment of a larger protein called HSP60. Given as a subcutaneous injection, its mechanism of action involves a Th1-Th2 shift. Clinical success has been demonstrated in prolonging the "honeymoon period" for people who already have type 1 diabetes.[33] The product is currently being tested in newly diagnosed type 1 diabetes adult patients. Ownership of the drug has changed hands several times over the last decade. In 2007, Clal Biotechnology Industries (CBI) Ltd., an Israeli investment group in the field of life sciences, purchased the product from the German company, DeveloGen. In June 2010, Andromeda Biotech announced that Teva Pharmaceutical Industries Ltd. decided to exercise its option to invest in Andromeda Biotech Ltd. [34] In return, Teva will commercialize the product which is currently in Phase 3 clinical studies in the USA, Europe, Israel, and South Africa.

Intra-nasal insulin

There is pre-clinical evidence that a Th1-Th2 shift can be induced by administration of insulin directly onto the immune tissue in the nasal cavity. This observation has led to a clinical trial, called INIT II, which began in late 2006, based in Australia and New Zealand.

BCG research

Tumor necrosis factor-alpha, or TNF-α, is part of the immune system. It helps the immune system distinguish self from non-self tissue. People with type 1 diabetes are deficient in this substance. Dr. Denise Faustman theorizes that giving Bacillus Calmette-Guérin (BCG), an inexpensive generic drug used to immunize against Mycobacterium tuberculosis, would have the same impact as injecting diabetic mice with Freund's Adjuvant, which stimulates TNF-α production. TNF-α kills the white blood cells responsible for destroying beta cells, and thus prevents, or reverses diabetes.[35] She has reversed diabetes in laboratory mice with this technique, but was only able to receive funding for subsequent research from The Iaccoca Foundation, founded by Lee Iacocca in honor of his late wife, who died from diabetes complications. Human trials are set to begin in 2008.

Diamyd

Diamyd is the name of a vaccine being developed by Diamyd Medical. Injections with GAD65, an autoantigen involved in type 1 diabetes, has in clinical trials delayed the destruction of beta cells for at least 30 months, without serious adverse effects. Patients treated with the substance showed higher levels of regulatory cytokines, thought to protect the beta cells.[36] Phase III trials are under way in the USA [37] and in Europe, with most sites actively pursuing participants.[38][39][40] Two prevention studies, where the vaccine is given to persons who have not yet developed diabetes are underway[41][42][43].

See also

Further reading

References

  1. ↑ "Diabetes Blue Circle Symbol". International Diabetes Federation. 17 March 2006. http://www.diabetesbluecircle.org. 
  2. ↑ ""Type 1 Diabetes Mellitus"". http://autoimmune.pathology.jhmi.edu/diseases.cfm?systemID=3&DiseaseID=23. Retrieved 2008-08-04. 
  3. ↑ 3.0 3.1 Cooke DW, Plotnick L (November 2008). "Type 1 diabetes mellitus in pediatrics". Pediatr Rev 29 (11): 374–84; quiz 385. doi:10.1542/pir.29-11-374. PMID 18977856. 
  4. ↑ ""One Step Closer to a Cure—Interview; Patrick Perry, Saturday Evening Post"". http://chinese-school.netfirms.com/diabetes-type-1-cure.html. Retrieved 2008-11-02. 
  5. ↑ BMI & Diabetes. Drexel U. (Report). Retrieved November 25, 2009.
  6. ↑ Mikael Knip, "Diet, Gut, and Type 1 Diabetes: Role of Wheat-Derived Peptides?", Diabetes, Aug. 2009.
  7. ↑ http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=222100
  8. ↑ "Nature Immunology 3", 338 - 340 (2002), doi:10.1038/ni0402-338
  9. ↑ "Donner", "Horst"; "Harald Rau, Paul G. Walfish, Jens Braun, Thorsten Siegmund, Reinhard Finke, Jürgen Herwig, Klaus H. Usadel and Klaus Badenhoop" ("2007"). ""CTLA4 Alanine-17 Confers Genetic Susceptibility to Graves’ Disease and to type 1 Diabetes Mellitus"". "The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 1 143-146". "The Journal of Clinical Endocrinology & Metabolism". http://jcem.endojournals.org/cgi/content/abstract/82/1/143. Retrieved 2008-02-06. 
  10. ↑ Hana Malcova, Zdenek Sumnik, Pavel Drevinek, Jitrenka Venhacova, Jan Lebl, Ondrej Cinek (October 7, 2005). "Absence of breast-feeding is associated with the risk of type 1 diabetes: a case–control study in a population with rapidly increasing incidence". European Journal of Pediatrics 165 (Volume 165, Number 2 / February, 2006): 114–119. doi:10.1007/s00431-005-0008-9. ISSN 0340-6199 (print) ISSN 1432-1076 (online). PMID 16211397. http://www.springerlink.com/content/b302557w3q56t532/. 
  11. ↑ content.nejm.org
  12. ↑ Type 1 Diabetes in Adults: Principles and Practice, Informa Healthcare, 2008, p. 27.
  13. ↑ "www.who.int" (pdf). World Health Organization. http://www.who.int/diabetes/publications/Definition%20and%20diagnosis%20of%20diabetes_new.pdf. 
  14. ↑ World Health Organisation Department of Noncommunicable Disease Surveillance (1999). "Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications" (PDF). http://whqlibdoc.who.int/hq/1999/WHO_NCD_NCS_99.2.pdf. 
  15. ↑ ""Diabetes Care" January 2010". http://care.diabetesjournals.org/content/33/Supplement_1/S3.full. Retrieved 2010-01-29. 
  16. ↑ Saydah SH, Miret M, Sung J, Varas C, Gause D, Brancati FL (August 2001). "Postchallenge hyperglycemia and mortality in a national sample of U.S. adults". Diabetes Care 24 (8): 1397–402. doi:10.2337/diacare.24.8.1397. PMID 11473076. 
  17. ↑ Santaguida PL, Balion C, Hunt D, Morrison K, Gerstein H, Raina P, Booker L, Yazdi H. "Diagnosis, Prognosis, and Treatment of Impaired Glucose Tolerance and Impaired Fasting Glucose". Summary of Evidence Report/Technology Assessment, No. 128. Agency for Healthcare Research and Quality. http://www.ahrq.gov/clinic/epcsums/impglusum.htm. Retrieved 2008-07-20. 
  18. ↑ Daneman D (March 2006). "Type 1 diabetes". Lancet 367 (9513): 847–58. doi:10.1016/S0140-6736(06)68341-4. PMID 16530579. 
  19. ↑ Borch-Johnsen K, Joner G, Mandrup-Poulsen T, et al. (November 1984). "Relation between breast-feeding and incidence rates of insulin-dependent diabetes mellitus. A hypothesis". Lancet 2 (8411): 1083–6. doi:10.1016/S0140-6736(84)91517-4. PMID 6150150. 
  20. ↑ Naim Shehadeh, Raanan Shamir, Moshe Berant, Amos Etzioni (2001). "Insulin in human milk and the prevention of type 1 diabetes". Pediatric Diabetes 2 (4): 175–7. doi:10.1034/j.1399-5448.2001.20406.x. PMID 15016183. 
  21. ↑ Virtanen SM, Knip M (December 2003). "Nutritional risk predictors of beta cell autoimmunity and type 1 diabetes at a young age". The American Journal of Clinical Nutrition 78 (6): 1053–67. PMID 14668264. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=14668264. 
  22. ↑ Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM (November 2001). "Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study". Lancet 358 (9292): 1500–3. doi:10.1016/S0140-6736(01)06580-1. PMID 11705562. 
  23. ↑ Elliott RB, Pilcher CC, Fergusson DM, Stewart AW (1996). "A population based strategy to prevent insulin-dependent diabetes using nicotinamide". Journal of Pediatric Endocrinology & Metabolism 9 (5): 501–9. PMID 8961125. 
  24. ↑ Dr James R Wright, Jr MD, in The Lancet, Volume 359, Issue 9313
  25. ↑ Pancreas Transplantation: Indications and Consequences
  26. ↑ "Islet cell transplant: Experimental treatment for type 1 diabetes - MayoClinic.com". http://www.mayoclinic.com/health/islet-cell-transplant/DA00046. Retrieved 2007-06-04. 
  27. ↑ Heart Disease Prevention. Google's Blogspot. (Report). Retrieved Nov 26 2009.
  28. ↑ Sridevi Devaraj, Nicole Glaser, Steve Griffen, Janice Wang-Polagruto, Eric Miguelino and Ishwarlal Jialal; "Increased Monocytic Activity and Biomarkers of Inflammation in Patients With Type 1 Diabetes"; Diabetes 2006 March 55: 774-779.
  29. ↑ Viktoria Granberg, MD, Niels Ejskjaer, MD, PHD, Mark Peakman, MD, PHD and Göran Sundkvist, MD, PHD; "Autoantibodies to Autonomic Nerves Associated With Cardiac and Peripheral Autonomic Neuropathy"; Diabetes Care 2005 28: 1959-1964.
  30. ↑ "Type 2 Diabetes Overview". Web MD. http://diabetes.webmd.com/guide/type-2-diabetes. 
  31. ↑ Diabetic Rockstar Inc www.diabeticrockstar.com
  32. ↑ jci.org
  33. ↑ interscience.wiley.com
  34. ↑ http://www.andromedabio.com/page.php?pageID=67
  35. ↑ Ryu, S; Shinichiro Ryu, Shohta Kodama, Kazuko Ryu, David A. Schoenfeld & Denise L. Faustman (July 1, 2001). "Reversal of established autoimmune diabetes by restoration of endogenous β cell function.". J. Clin. Invest. 108 (1): 63–72. doi:10.1172/JCI12335. PMID 11435458. PMC 209340. http://www.jci.org/articles/view/12335. 
  36. ↑ New England Journal of Medicine: GAD Treatment and Insulin Secretion in Recent-Onset type 1 Diabetes
  37. ↑ Diamyd US Phase III Trial
  38. ↑ Diamyd European Phase III Trial
  39. ↑ Further Evidence for Lasting Immunological Efficacy of Diamyd Diabets Vaccine
  40. ↑ Diamyd Announces Completion of type 1 Diabetes Vaccine Trial with Long Term Efficcacy Demonstrated at 30 Months
  41. ↑ MSNBC News: Pioneering Diamyd(r) Study to Prevent Childhood Diabetes Approved
  42. ↑ Diamyd press release: Diamyd approved for groundbreking study in Norway
  43. ↑ Clinicaltrials.gov: Diabetes Prevention - Immune Tolerance (DIAPREV-IT)

External links

Diabetes (E10-E14, 250)
Types of diabetes

Prediabetes (Impaired fasting glucose, Impaired glucose tolerance)

Type 1 · Type 2 · MODY · NDM (Transient, Permanent)

Diabetes and pregnancy: Gestational diabetes
Blood tests
Blood sugar · Glycosylated hemoglobin · Glucose tolerance test · Fructosamine
Diabetes management
Diabetic diet  · Anti-diabetic drugs · Insulin therapy · Glossary of diabetes
Complications/prognosis
Diabetic comas (Diabetic hypoglycemia, Diabetic ketoacidosis, Nonketotic hyperosmolar) · Diabetic angiopathy · Diabetic myonecrosis · Diabetic nephropathy · Diabetic neuropathy · Diabetic retinopathy · Diabetic cardiomyopathy · Diabetic dermadrome (Diabetic dermopathy, Diabetic bulla, Diabetic cheiroarthropathy, Neuropathic ulcer)

: END

anat/phys/devp/horm/cell

noco(d)//tumr, sysi/

proc, drug (A10/H1/H2//)
Immune disorders: hypersensitivity and autoimmune diseases (279.5-6)
Type I/allergy/atopy
(IgE)
Foreign
Atopic dermatitis · Allergic urticaria · Hay fever · Allergic asthma · Anaphylaxis · Food allergy (Milk, Egg, Peanut, Tree nut, Seafood, Soy, Wheat), Penicillin allergy
Autoimmune
none
Type II/ADCC
(IgM, IgG)
Foreign
Pernicious anemia · Hemolytic disease of the newborn
Autoimmune
Cytotoxic
Autoimmune hemolytic anemia · Idiopathic thrombocytopenic purpura  · Bullous pemphigoid  · Pemphigus vulgaris · Rheumatic fever · Goodpasture's syndrome
Type III
(Immune complex)
Foreign
Henoch–Schönlein purpura · Hypersensitivity vasculitis · Reactive arthritis · Rheumatoid arthritis · Farmer's lung · Post-streptococcal glomerulonephritis · Serum sickness · Arthus reaction
Autoimmune
Systemic lupus erythematosus · Subacute bacterial endocarditis
Type IV/cell-mediated
(T-cells)
Foreign
Allergic contact dermatitis · Mantoux test
Autoimmune
Diabetes mellitus type 1 · Hashimoto's thyroiditis · Guillain–Barré syndrome  · Multiple sclerosis  · Coeliac disease · Giant cell arteritis
GVHD
Transfusion-associated graft versus host disease
Unknown/
multiple
Foreign
Hypersensitivity pneumonitis (Allergic bronchopulmonary aspergillosis) · Transplant rejection · Latex allergy (I+IV)
Autoimmune
Sjögren's syndrome · Autoimmune hepatitis · Autoimmune polyendocrine syndrome (APS1, APS2) · Autoimmune adrenalitis · Systemic autoimmune disease

: LMC

cell/phys/auag/auab/comp,imrc,tcrp

imdf/ipig/hyps/tumr

proc, drug(/4)

Diabetes mellitus type 1