Diabetes mellitus type 1

Diabetes mellitus type 1
Diabetes type 1
Classification and external resources

Universal blue circle symbol for diabetes.[1]
ICD-10 E10
ICD-9 250.01
OMIM 222100
DiseasesDB 3649
MedlinePlus 000305
eMedicine med/546
MeSH D003922

Diabetes mellitus type 1 (Type 1 diabetes, T1DM, IDDM, or, formerly, 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 are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss.[3]

Incidence varies from 8-17/100,000 in Northern Europe and the U.S., with a high of about 35/100,000 in Scandinavia, to a low of 1/100,000 in Japan and China.[4]

Eventually, type 1 diabetes is fatal unless treated with insulin. Injection is the most common method of administering insulin; other methods are insulin pumps and inhaled insulin. Pancreatic transplants have been used. Pancreatic islet cell transplantation is experimental, though growing.[5]

Most people who develop type 1 are otherwise healthy.[6] Although the cause of type 1 diabetes is still not fully understood, it is believed to be of immunological origin.

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 is not intended to significantly impair normal activities, and can be done adequately if sufficient patient training, awareness, appropriate care, discipline in testing and dosing of insulin is taken. However, treatment remains quite burdensome for many people. Complications may be associated with both low blood sugar and high blood sugar, both largely due to the non-physiological manner in which insulin is replaced. Low blood sugar may lead to seizures or episodes of unconsciousness and requires emergency treatment. High blood sugar may lead to increased fatigue and can also result in long term damage to organs.


Brittle diabetes, also known as unstable diabetes or labile diabetes, refers to a type of insulin-dependent diabetes characterized by dramatic and recurrent swings in glucose levels, often occurring for no apparent reason.[7] The result can be irregular and unpredictable hyperglycemias, frequently with ketosis, and sometimes serious hypoglycemias. Brittle diabetes occurs no more frequently than in 1% to 2% of diabetics.[8]

Signs and symptoms

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


Diabetes type I is induced by a combination of genetic susceptibility, a diabetogenic trigger and exposure to a driving antigen.[9]


Type 1 diabetes is a polygenic disease, meaning many different genes contribute to its onset. 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. Certain variants of this gene increases the risk for decreased histocompatibility characteristic of type 1. Such variants include DRB1 0401, DRB1 0402, DRB1 0405, DQA 0301, DQB1 0302 and DQB1 0201, which are common in North Americans of European ancestry and in Europeans.[10] There are also variants that appear to be protective.[10]

The risk of a child developing type 1 diabetes is approximately 10% if the father has it, approximately 10% if a sibling has it, approximately 4% if the mother has type 1 diabetes and is/was aged 25 or younger when the child is/was born, and approximately 1% if the mother is/was over 25 years old when the child is/was born.[11]


Environmental factors can 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 exactly the 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.[12] Other indications of environmental influence include the presence of a 10-fold difference in difference among Caucasians living in different areas of Europe, and a tendency to acquire the incidence of the disease of the destination country for people who migrate.[9]


One theory, discussed by DeLisa Fairweather & Noel R. Rose, among others,[13] 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 Rubella 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[14] 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.


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.[15]

Some researchers believe that the autoimmune response is influenced by antibodies against cow's milk proteins.[16] 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).[citation needed]

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.

Short breast-feeding period and short attendance to day care is associated with the risk of type 1 diabetes in Czech children.[17]

Chemicals and drugs

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 pathophysiology in diabetes type I is basically a destruction of beta cells in the pancreas, regardless of which risk factors or causative entities have been present.

Individual risk factors can have separate pathophysiological processes to, in turn, cause this beta cell destruction. Still, a process that appears to be common to most risk factors is an autoimmune response towards beta cells, involving an expansion of autoreactive CD4+ and CD8+ T helper cells, autoantibody-producing B cells and activation of the innate immune system.[10]


2006 WHO Diabetes criteria[18]  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:[19]

  • Fasting plasma glucose level at or above 7.0 mmol/L (126 mg/dL).
  • Plasma glucose at or above 11.1 mmol/L (200 mg/dL) two hours after a 75 g oral glucose load as in a glucose tolerance test.
  • Symptoms of hyperglycemia and casual plasma glucose at or above 11.1 mmol/L (200 mg/dL).
  • Glycated hemoglobin (hemoglobin A1C) at or above 6.5. (This criterion was recommended by the American Diabetes Association in 2010, although it has yet to be adopted by the WHO.)[20]

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 may be 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.[21] 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 and cardiovascular disease.[22]


The appearance of diabetes-related autoantibodies has been shown to be able to predict the appearance of diabetes type 1 before any hyperglycemia arises, the main ones being islet cell autoantibodies, insulin autoantibodies, autoantibodies targeting the 65 kDa isoform of glutamic acid decarboxylase (GAD) and autoantibodies targeting the phosphatase-related IA-2 molecule.[9] Per definition, the diagnosis of diabetes type 1 can be made first at the appearance of clinical symptoms and/or signs, but the emergence of autoantibodies may itself be termed latent autoimmune diabetes. Not everyone with autoantibodies progress to diabetes type 1, but the risk increases with the number of antibody types, with three to four antibody types giving a risk of progressing to diabetes type 1 of 60%-100%.[9] The time interval from emergence of autoantibodies to frank diabetes type 1 can be a few months in infants and young children, but in some people it may take years - in some cases more than 10 years.[9] Islet cell autoantibodies are detected by conventional immunofluorescence while the rest are measured with specific radiobinding assays.[9]


Type 1 diabetes is not currently preventable.[23] Some researchers believe that diabetes type 1 might be prevented at the latent autoimmune stage, before it starts destroying beta cells.[10]

Immunosuppressive drugs

Cyclosporine A, an immunosuppressive agent, has apparently halted destruction of beta cells (on the basis of reduced insulin usage), but its nephrotoxicity and other side effects make it highly inappropriate for long-term use.[10]

Anti-CD3 antibodies, including teplizumab and otelixizumab, had suggested evidence of preserving insulin production (as evidenced by sustained C-peptide production) in newly diagnosed type 1 diabetes patients.[10] A probable mechanism of this effect was believed to be preservation of regulatory T cells that suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self-antigens.[10] The duration of the effect is still unknown, however.[10] In 2011, Phase III studies with otelixizumab and teplizumab both failed to show clinical efficacy.[24][25]

An anti-CD20 antibody, rituximab, inhibits B cells and has been shown to provoke C-peptide responses three months after diagnosis of type 1 diabetes, but long-term effects of this have not been reported.[10]


Some research has suggested that breastfeeding decreased the risk in later life;[26][27] various other nutritional risk factors are being studied, but no firm evidence has been found.[28] 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.[29]

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.[30]


Insulin therapy

Type 1 is treated with insulin replacement therapy—either via subcutaneous 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.[31] 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.

Treatment of diabetes focuses on lowering blood sugar or glucose (BG) to the near normal range, approximately 80–140 mg/dl (4.4-7.8 mmol/L).[32] The ultimate goal of normalizing BG is to avoid long term complications that affect the nervous system (e.g. peripheral neuropathy leading to pain and/or loss of feeling in the extremities), and the cardiovascular system (e.g. heart attacks, vision loss). There are two primary types of diabetes, type 1 and type 2. People with type 1 diabetes always need to take insulin. Treatment with insulin can lead to low BG, or hypoglycemia, i.e. BG less than 70 mg/dl (3.9 mmol/L). Hypoglycemia is a very common occurrence in people with diabetes, usually the result of a mismatch in the balance among insulin, food and physical activity, although the non-physiological method of delivery also plays a role.

Pancreas transplantation

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 generally only used 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 cyclosporine. 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.[33]

Islet cell transplantation

Experimental replacement of beta cells (by transplant or from stem cells) is being investigated in several research programs. Islet cell transplantation is 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.[34] 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.


Complications of poorly-managed type 1 diabetes mellitus may include cardiovascular disease, diabetic neuropathy, diabetic retinopathy among others. However, there is some evidence that cardiovascular disease[35] as well as neuropathy[36] may, in fact, have an autoimmune basis as well.


Studies conducted in the United States[37] and Europe[38] showed that drivers with type 1 diabetes had twice as many collisions as their non-diabetic spouses, demonstrating the increased risk of driving collisions in the type 1 diabetes population. Diabetes can compromise driving safety in several ways. First, long-term complications of diabetes can interfere with the safe operation of a vehicle. For example, diabetic retinopathy (loss of peripheral vision or visual acuity), or peripheral neuropathy (loss of feeling in the feet) can impair a driver’s ability to read street signs, control the speed of the vehicle, apply appropriate pressure to the brakes, etc.

Second, hypoglycemia can affect a person’s thinking process, coordination, and state of consciousness.[39][40] This disruption in brain functioning is called neuroglycopenia. Studies have demonstrated that the effects of neuroglycopenia impair driving ability.[39][41] A study involving people with type 1 diabetes found that individuals reporting two or more hypoglycemia-related driving mishaps differ physiologically and behaviorally from their counterparts who report no such mishaps.[42] For example, during hypoglycemia, drivers who had two or more mishaps reported fewer warning symptoms, their driving was more impaired, and their body released less epinephrine (a hormone that helps raise BG). Additionally, individuals with a history of hypoglycemia-related driving mishaps appear to use sugar at a faster rate[43] and are relatively slower at processing information.[44] These findings indicate that although anyone with type 1 diabetes may be at some risk of experiencing disruptive hypoglycemia while driving, there is a subgroup of type 1 drivers who are more vulnerable to such events.

Given the above research findings, it is recommended that drivers with type 1 diabetes with a history of driving mishaps should never drive when their BG is less than 70 mg/dl. Instead, these drivers are advised to treat hypoglycemia and delay driving until their BG is above 90 mg/dl.[42] Such drivers should also learn as much as possible about what causes their hypoglycemia, and use this information to avoid future hypoglycemia while driving.

Studies funded by the National Institutes of Health (NIH) have demonstrated that face-to-face training programs designed to help individuals with type 1 diabetes better anticipate, detect, and prevent extreme BG can reduce the occurrence of future hypoglycemia-related driving mishaps.[45][46][47] An internet-version of this training has also been shown to have significant beneficial results.[48] Additional NIH funded research to develop internet interventions specifically to help improve driving safety in drivers with type 1 diabetes is currently underway.[49]


Type 1 diabetes causes an estimated 5–10% of all diabetes cases[50] or 11–22 million worldwide.[23] In 2006 it affected 440 thousand children under 14 years of age and was the primary cause of diabetes in those less than 10 years of age.[51] The incidence of type 1 diabetes has been increasing by about 3% per year.[51]

Rates vary widely by country. In Finland, the incidence is a high of 35/100,000 per year, in Japan and China a low of 1–3/100,000 per year, and in Northern Europe and the U.S., an intermediate 8–17/100,000 per year.[4][52]

Type 1 diabetes was previously known as juvenile diabetes to distinguish it from type 2 diabetes, which generally has a later onset; however, the majority of new-onset type 1 diabetes is seen in adults. 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. Adult-onset type 1 autoimmune diabetes is two to three times more common than classic childhood-onset autoimmune diabetes.[53]


In the US in 2008, there were about one million people diagnosed with type 1 diabetes. The disease was estimated to cause $10.5 billion in annual medical costs ($875 per month per diabetic) and an additional $4.4 billion in indirect costs ($366 per month per diabetic).[54]



The Juvenile Diabetes Research Foundation (JDRF) is the leading charitable funder of research into type 1 diabetes in the world. It has offices in the UK, Denmark, USA, Canada, Australia, Israel, Mexico and India. 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 Diabetes Research Institute Foundation is the only organization solely dedicated to curing diabetes. Founded by a group of parents of children with diabetes who wanted to put an end to type 1 diabetes, the Diabetes Research Institute Foundation has grown into an international coalition of business leaders, celebrities, research scientists, clinicians, families and other concerned individuals who have been a strong voice for cure-focused research. Supported by private philanthropy, the DRI Foundation has been and continues to be the organization of choice for those who are serious, passionate and committed to finding a cure for diabetes. Its mission is to provide the Diabetes Research Institute with the funding necessary to cure diabetes now.

The International Diabetes Federation is a worldwide alliance of over 160 countries to address diabetes research and treatment. The American Diabetes Association funds some type 1 research along with other a variety of diabetes-related research (not necessarily cure-specific) including type 2 diabetes, gestational diabetes and others) that looks at treatments, prevention, as well as some cure-specific research. Diabetes Australia is involved in promoting research and education in Australia on both type 1 and type 2 diabetes. 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.

GAD65 vaccine

Injections with a vaccine containing GAD65, an autoantigen involved in type 1 diabetes, has in clinical trials delayed the destruction of beta cells when treated within six months of diagnosis.[10] Patients treated with the substance showed higher levels of regulatory cytokines, thought to protect the beta cells.[55] Phase III trials are under way in the USA [56] and in Europe.[57][58][59] Two prevention studies, where the vaccine is given to persons who have not yet developed diabetes are underway.[60][61][62]

T helper cell shift

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 type 1 T helper cell (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 T-cells. Instead of pro-inflammatory cytokines, the T-cells begin to release cytokines that inhibit inflammation.[63] This phenomenon is commonly known as "acquired immune tolerance".

See also

  • Kara Neumann case – "treatment" by prayers case resulting in death
  • List of people with diabetes mellitus type 1
  • Type 1 Diabetes Association


  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. ^ a b 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. ^ a b Kasper, Dennis L; Braunwald, Eugene; Fauci, Anthony; et al. (2005). Harrison's Principles of Internal Medicine, 16th ed.. New York: McGraw-Hill. ISBN 0-07-139140-7. 
  5. ^ "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. 
  6. ^ BMI & Diabetes (Report). Drexel U. http://www.idea.library.drexel.edu/bitstream/1860/2806/1/Markowitz_Jessica.pdf. Retrieved November 25, 2009. 
  7. ^ "Diabetes Mellitus (DM): Diabetes Mellitus and Disorders of Carbohydrate Metabolism: Merck Manual Professional". Merck.com. http://www.merck.com/mmpe/sec12/ch158/ch158b.html#sec12-ch158-ch158b-1206. Retrieved 2010-07-30. 
  8. ^ . PMID 406527. 
  9. ^ a b c d e f Knip, M.; Veijola, R.; Virtanen, S. M.; Hyoty, H.; Vaarala, O.; Akerblom, H. K. (2005). "Environmental Triggers and Determinants of Type 1 Diabetes". Diabetes 54: S125–S136. doi:10.2337/diabetes.54.suppl_2.S125. PMID 16306330.  edit
  10. ^ a b c d e f g h i j Bluestone, J. A.; Herold, K.; Eisenbarth, G. (2010). "Genetics, pathogenesis and clinical interventions in type 1 diabetes". Nature 464 (7293): 1293. Bibcode 2010Natur.464.1293B. doi:10.1038/nature08933. PMID 20432533.  edit
  11. ^ Genetics & Diabetes, Diabetes Information. Dr. Warram. Joslin Diabetes Center and Joslin Clinic
  12. ^ http://www.ncbi.nlm.nih.gov/omim/222100
  13. ^ "Nature Immunology 3", 338 - 340 (2002), doi:10.1038/ni0402-338
  14. ^ "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. 
  15. ^ Mikael Knip, "Diet, Gut, and Type 1 Diabetes: Role of Wheat-Derived Peptides?", Diabetes, Aug. 2009.
  16. ^ content.nejm.org
  17. ^ 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. PMID 16211397. (print) (online). http://www.springerlink.com/content/b302557w3q56t532/. 
  18. ^ "Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycemia" (pdf). World Health Organization. www.who.int. 2006. http://www.who.int/diabetes/publications/Definition%20and%20diagnosis%20of%20diabetes_new.pdf. Retrieved 2011-02-20. 
  19. ^ 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. 
  20. ^ ""Diabetes Care" January 2010". American Diabetes Association. http://care.diabetesjournals.org/content/33/Supplement_1/S3.full. Retrieved 2010-01-29. 
  21. ^ 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. 
  22. ^ 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. 
  23. ^ a b "Diabetes". World Health Organization. http://www.who.int/mediacentre/factsheets/fs312/en/index.html. Retrieved 24 January 2011. 
  24. ^ Biospace:Tolerx, Inc. and GlaxoSmithKline (GSK) Announce Phase 3 Defend-1 Study of Otelixizumab in Type 1 Diabetes Did Not Meet Its Primary Endpoint
  25. ^ Macrogenics press release: MacroGenics and Lilly Announce Pivotal Clinical Trial of Teplizumab Did Not Meet Primary Efficacy Endpoint
  26. ^ 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. 
  27. ^ 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. 
  28. ^ 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. 
  29. ^ 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. 
  30. ^ 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. doi:10.1515/JPEM.1996.9.5.501. PMID 8961125. 
  31. ^ Dr James R Wright, Jr MD, in The Lancet, Volume 359, Issue 9313
  32. ^ American Diabetes Association Clinical Guidelines, 2010.
  33. ^ Pancreas Transplantation: Indications and Consequences
  34. ^ "Islet cell transplant: Experimental treatment for type 1 diabetes - MayoClinic.com". Archived from the original on April 10, 2007. http://web.archive.org/web/20070410214823/http://www.mayoclinic.com/health/islet-cell-transplant/DA00046. Retrieved 2007-06-04. 
  35. ^ 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.
  36. ^ 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.
  37. ^ Songer, TJ. Low blood sugar and motor vehicle crashes in persons with type 1 diabetes, Annu Proc Assoc Adv Automotive Med, 46:424-427 (2002)
  38. ^ Cox DJ, Penberthy JK, Zrebiec J, Weinger K, Aikens JE, Frier BM, Stetson B, DeGroot M, Trief P, Schaechinger H, Hermanns H, Gonder-Frederick LA & Clarke WL (2003). Diabetes and Driving Mishaps: Frequency and correlations from a multinational survey. Diabetes Care, 26(8), 2329–2334.
  39. ^ a b Cox DJ, Gonder-Frederick LA & Clarke WL (1993). Driving decrements in type 1 diabetes during moderate hypoglycemia. Diabetes, 42(2), 239-243. PMID: 8425660
  40. ^ Clarke WL, Cox DJ, Gonder-Frederick LA & Kovatchev B (1999). Hypoglycemia and the Decision to Drive a Motor Vehicle by Persons With Diabetes. JAMA, 282(8), 750-754.
  41. ^ Cox D, Gonder-Frederick LA, Kovatchev BP, Julian DM & Clarke WL (2000). Progressive hypoglycemia’s impact on driving simulation performance. Diabetes Care, 23(2), 163-170.
  42. ^ a b Cox DJ, Kovatchev BP, Anderson SA, Clarke WL & Gonder-Frederick L (2010). type 1 diabetic drivers with and without a history of recurrent hypoglycemia-related driving mishaps: Physiological and performance differences during euglycemia and the induction of hypoglycemia. Diabetes Care, PMID: 20699432
  43. ^ Cox, DJ, Gonder-Frederick LA, Kovatchev BP, Clarke WL, The metabolic demands of driving for drivers with type 1 diabetes mellitus, Diabetes/Metabolism Research and Review 18(5):381-385 (2002)
  44. ^ Campbell LK, Gonder-Frederick LA, Broshek DK, Kovatchev BP, Anderson S, Clarke WL & Cox DJ (2010). Neurocognitive differences between drivers with type 1 diabetes with and without a recent history of recurrent driving mishaps. International Journal of Diabetes, 2(2), 73-77. NIHMS[211748]
  45. ^ Cox DJ, Gonder-Frederick LA, Julian D & Clarke W (1994). Long-term follow-up evaluation of blood glucose awareness training. Diabetes Care, 17(1), 1-5. PMID: 8112183
  46. ^ Cox DJ, Gonder-Frederick LA, Polonsky W, Schlundt D, Julian D, Kovatchev B, Clarke WL (2001). Blood Glucose Awareness Training (BGAT-II): Long term benefits. Diabetes Care, 24(4), 637-642. PMID: 11315822
  47. ^ Broers S., le Cessie S., van Vliet KP, Spinhoven P., van der Ven NC, Radder JK, Blood glucose awareness training in Dutch type 1 diabetes patients, Diabet. Med. 19(2):157-161 (2002)
  48. ^ Cox DJ, Ritterband L, Magee J, Clarke W & Gonder-Frederick L (2008). Blood Glucose Awareness Training Delivered Over The Internet. Diabetes Care, 31(8), 1527-1528. PMC2494647
  49. ^ http://www.DiabetesDriving.com Diabetes Driving.
  50. ^ Daneman, D (2006-03-11). "Type 1 diabetes". Lancet 367 (9513): 847–58. doi:10.1016/S0140-6736(06)68341-4. PMID 16530579. 
  51. ^ a b Aanstoot, HJ; Anderson, BJ, Daneman, D, Danne, T, Donaghue, K, Kaufman, F, Réa, RR, Uchigata, Y (2007 Oct). "The global burden of youth diabetes: perspectives and potential". Pediatric diabetes. 8 Suppl 8 (s8): 1–44. doi:10.1111/j.1399-5448.2007.00326.x. PMID 17767619. 
  52. ^ Soltesz, G; Patterson, CC, Dahlquist, G, EURODIAB Study, Group (2007 Oct). "Worldwide childhood type 1 diabetes incidence--what can we learn from epidemiology?". Pediatric diabetes. 8 Suppl 6 (s6): 6–14. doi:10.1111/j.1399-5448.2007.00280.x. PMID 17727380. 
  53. ^ Type 1 Diabetes in Adults: Principles and Practice, Informa Healthcare, 2008, p. 27.
  54. ^ Johnson, Linda (2008). "Study: Cost of diabetes $218B". The Associated Press. http://www.usatoday.com/news/health/2008-11-18-diabetes-cost_N.htm. 
  55. ^ New England Journal of Medicine: GAD Treatment and Insulin Secretion in Recent-Onset type 1 Diabetes
  56. ^ Diamyd US Phase III Trial
  57. ^ Diamyd European Phase III Trial
  58. ^ Further Evidence for Lasting Immunological Efficacy of Diamyd Diabets Vaccine
  59. ^ Diamyd Announces Completion of type 1 Diabetes Vaccine Trial with Long Term Efficcacy Demonstrated at 30 Months
  60. ^ MSNBC News: Pioneering Diamyd(r) Study to Prevent Childhood Diabetes Approved
  61. ^ Diamyd press release: Diamyd approved for groundbreking study in Norway
  62. ^ Clinicaltrials.gov: Diabetes Prevention - Immune Tolerance (DIAPREV-IT)
  63. ^ jci.org

External links

Wikimedia Foundation. 2010.

Игры ⚽ Поможем решить контрольную работу

Look at other dictionaries:

  • Diabetes mellitus type 2 — Classification and external resources Universal blue circle symbol for diabetes.[1] ICD 10 …   Wikipedia

  • Diabetes mellitus — Diabetes redirects here. For other uses, see Diabetes (disambiguation). Diabetes mellitus Classification and external resources Universal blue circle symbol for diabetes.[1] …   Wikipedia

  • Diabetes mellitus and deafness — Classification and external resources OMIM 520000 DiseasesDB 33761 Diabetes mellitus and deafness (DAD) or maternally inherited diabetes and …   Wikipedia

  • Diabetes mellitus and pregnancy — For women with diabetes mellitus, pregnancy can present some particular challenges for both mother and child. If the woman who is pregnant has diabetes, it can cause early labor, birth defects, and very large babies. Planning in advance is… …   Wikipedia

  • diabetes mellitus — [mə līt′əs] n. 〚ModL, lit., honey diabetes < L mellitus, of honey, honeyed < mel, honey: see MILDEW〛 a chronic form of diabetes involving an insulin deficiency and characterized by an excess of sugar in the blood and urine, and by hunger, thirst …   Universalium

  • Diabetes mellitus tipo 2 — Saltar a navegación, búsqueda La diabetes mellitus tipo 2 o diabetes senil conocida anteriormente como diabetes no insulinodependiente es una enfermedad inmunologica caracterizada por altos niveles de glucosa en la sangre (hiperglicemia) debido a …   Wikipedia Español

  • diabetes mellitus — diabetes mel·li·tus mel ət əs n a variable disorder of carbohydrate metabolism caused by a combination of hereditary and environmental factors and usu. characterized by inadequate secretion or utilization of insulin, by excessive urine production …   Medical dictionary

  • Diabetes mellitus — diabetes di a*be tes, n. [NL., from Gr. ?, fr. ? to pass or cross over. See {Diabase}.] (Med.) Any of several diseases which is attended with a persistent, excessive discharge of urine; when used without qualification, the term usually refers to… …   The Collaborative International Dictionary of English

  • diabetes mellitus — diabetes di a*be tes, n. [NL., from Gr. ?, fr. ? to pass or cross over. See {Diabase}.] (Med.) Any of several diseases which is attended with a persistent, excessive discharge of urine; when used without qualification, the term usually refers to… …   The Collaborative International Dictionary of English

  • diabetes mellitus — diabetes di a*be tes, n. [NL., from Gr. ?, fr. ? to pass or cross over. See {Diabase}.] (Med.) Any of several diseases which is attended with a persistent, excessive discharge of urine; when used without qualification, the term usually refers to… …   The Collaborative International Dictionary of English

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”