Diabetes mellitus type 1
|Diabetes type 1|
A blue circle, the symbol for diabetes.
|Classification and external resources|
Diabetes mellitus type 1 (also known as type 1 diabetes, or T1D; formerly insulin-dependent diabetes or juvenile diabetes) is a form of diabetes mellitus that results from the autoimmune destruction of the insulin-producing beta cells in the pancreas. 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.
The cause of diabetes mellitus type 1 is unknown. Type 1 diabetes can be distinguished from type 2 by autoantibody testing. The C-peptide assay, which measures endogenous insulin production, can also be used.
Administration of insulin is essential for survival. Insulin therapy must be continued indefinitely and does not usually impair normal daily activities. People are usually trained to manage their diabetes independently; however, for some this can be challenging. Untreated, diabetes can cause many complications. Acute complications include diabetic ketoacidosis and nonketotic hyperosmolar coma. Serious long-term complications include heart disease, stroke, kidney failure, foot ulcers and damage to the eyes. Furthermore, complications may arise from low blood sugar caused by excessive treatment.
Diabetes mellitus type 1 accounts for between 5% and 10% of cases of diabetes. Globally, the number of people with DM type 1 is unknown, although it is estimated that about 80,000 children develop the disease each year. Within the United States the number of affected persons is estimated at one to three million. The development of new cases vary by country and region; the lowest rates appears to be in Japan and China with approximately 1 person per 100,000 per year; the highest rates are found in Scandinavia where it is closer to 35 new cases per 100,000 per year. The United States and northern Europe[clarification needed] fall somewhere in between with 8-17 new cases per 100,000 per year.
- 1 Signs and symptoms
- 2 Cause
- 3 Pathophysiology
- 4 Diagnosis
- 5 Prevention
- 6 Management
- 7 Complications
- 8 Epidemiology
- 9 History
- 10 Society and culture
- 11 Research
- 12 Labile diabetes
- 13 References
- 14 External links
Signs and symptoms
Many type 1 diabetics are diagnosed when they present with diabetic ketoacidosis. The signs and symptoms of diabetic ketoacidosis include xeroderma (dry skin), rapid deep breathing, drowsiness, abdominal pain, and vomiting.
About 12 percent of people with type 1 diabetes have clinical depression.
The cause of type 1 diabetes is unknown. A number of explanatory theories have been put forward, and the cause may be one or more of the following: genetic susceptibility, a diabetogenic trigger, and/or exposure to an antigen.
Type 1 diabetes is a disease that involves many genes. Depending on locus or combination of loci, they 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 increase 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. Some variants also appear to be protective.
The risk of a child developing type 1 diabetes is about 10% if the father has it, about 10% if a sibling has it, about 4% if the mother has type 1 diabetes and was aged 25 or younger when the child was born, and about 1% if the mother was over 25 years old when the child was born.
Environmental factors can influence expression of type 1. For identical twins, when one twin had type 1 diabetes, the other twin only had it 30%–50% of the time. Despite having exactly the same genome, one twin had the disease, whereas the other did not; this suggests environmental factors, in addition to genetic factors, can influence the disease's prevalence. Other indications of environmental influence include the presence of a 10-fold difference in occurrence among Caucasians living in different areas of Europe, and that people tend to acquire the rate of disease of their particular destination country.
One theory proposes that type 1 diabetes is a virus-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. This vulnerability is not shared by everyone, for not everyone infected by the suspected virus develops type 1 diabetes. This has suggested presence of a genetic vulnerability 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 autoimmune reaction remains poorly understood.
Chemicals and drugs
Some chemicals and drugs selectively destroy pancreatic cells. Pyrinuron (Vacor), a rodenticide introduced in the United States in 1976, selectively destroys pancreatic beta cells, resulting in type 1 after ingestion. Pyrinuron was withdrawn from the U.S. market in 1979 but is still used in some countries. Streptozotocin (Zanosar), an antibiotic and antineoplastic agent used in chemotherapy for pancreatic cancer, 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 1 is 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+ T helper cells and CD8+ T cells, autoantibody-producing B cells and activation of the innate immune system.
|Condition||2 hour glucose||Fasting glucose||HbA1c|
|Normal||<7.8 (<140)||<6.1 (<110)||<42||<6.0|
|Impaired fasting glycaemia||<7.8 (<140)||≥6.1(≥110) & <7.0(<126)||42-46||6.0–6.4|
|Impaired glucose tolerance||≥7.8 (≥140)||<7.0 (<126)||42-46||6.0–6.4|
|Diabetes mellitus||≥11.1 (≥200)||≥7.0 (≥126)||≥48||≥6.5|
- 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 48 mmol/mol (≥ 6.5 DCCT %). (This criterion was recommended by the American Diabetes Association in 2010, although it has yet to be adopted by the WHO.)
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. 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.
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. Type 2 diabetes is characterized by insulin resistance, while type 1 diabetes is characterized by insulin deficiency, generally without insulin resistance. Another hallmark of type 1 diabetes is islet autoreactivity, which is generally measured by the presence of autoantibodies directed towards the beta cells.
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), autoantibodies targeting the phosphatase-related IA-2 molecule, and zinc transporter autoantibodies (ZnT8). By 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 progresses 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%. The time interval from emergence of autoantibodies to clinically diagnosable diabetes 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. Islet cell autoantibodies are detected by conventional immunofluorescence, while the rest are measured with specific radiobinding assays.
Cyclosporine A, an immunosuppressive agent, has apparently halted destruction of beta cells (on the basis of reduced insulin usage), but its kidney toxicity and other side effects make it highly inappropriate for long-term use.
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. 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. The duration of the effect is still unknown, however. In 2011, Phase III studies with otelixizumab and teplizumab both failed to show clinical efficacy, potentially due to an insufficient dosing schedule.
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.
Some research has suggested breastfeeding decreases the risk in later life; various other nutritional risk factors are being studied, but no firm evidence has been found. 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.
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 the niacinamide version, had less than half the diabetes onset incidence in a seven-year time span than did the general population, and an even lower incidence relative to those with antibodies as above, but who received no niacinamide.
As psychological stress may have a negative effect on diabetes, a number of measures have been recommended including: exercising, taking up a new hobby, or joining a charity among others.
There are four main types of insulin, rapid acting insulin, short acting insulin, intermediate acting insulin, and long acting insulin. The rapid acting insulin is used as a bolus dosage. The action onsets in 15 minutes with peak actions in 30 to 90 minutes. Short acting insulin action onsets within 30 minutes with the peak action around 2 to 4 hours. Intermediate acting insulin action onsets within 1 to 2 hours with peak action of 4 to 10 hours. Long acting insulin is usually given around bedtime. The action onset is roughly 1 to 2 hours with a sustained action of 24 hours.
Injections of insulin—either via subcutaneous injection or insulin pump— is necessary for those living with type 1 diabetes. There is no evidence that it can be treated by diet and exercise alone. In addition to insulin therapy dietary management is important. This includes keeping track of the carbohydrate content of food, 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. 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 with different onset or duration of action times.
Untreated type 1 diabetes commonly leads to coma, often from diabetic ketoacidosis, which is fatal if untreated. Diabetic ketoacidosis can cause cerebral edema (accumulation of liquid in the brain). This complication is life-threatening. Children are at an increased risk for cerebral edema, making ketoacidosis the most common cause of death in pediatric diabetes.
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). 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). This level of control over a prolonged period of time can be varied by a target HbA1c level of less than 7.5%.
People with type 1 diabetes always need to use insulin, but treatment can lead to low BG (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. Mild cases are self-treated by eating or drinking something high in sugar. Severe cases can lead to unconsciousness and are treated with intravenous glucose or injections with glucagon. Continuous glucose monitors can alert patients to the presence of dangerously high or low blood sugar levels, but technical issues have limited the effect these devices have had on clinical practice.
In some cases, a pancreas transplant can restore proper glucose regulation. However, the surgery and accompanying immunosuppression required may be more dangerous than continued insulin replacement therapy, so is generally only used 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, pancreas to a person with diabetes without any additional immunosuppressive therapy. However, pancreas transplants alone may be beneficial in people with extremely labile type 1 diabetes mellitus.
Islet cell transplantation
Islet cell transplantation may be an option for some people with type 1 diabetes that are not well controlled with insulin. Difficulties include finding donors that are a compatible, getting the new islets to survive, and the side effects from the medications used to prevent rejection. Success rates, defined as not needing insulin at 3 years follow the procedure occurred in 44% in on registry from 2010.
Complications of poorly managed type 1 diabetes mellitus may include cardiovascular disease, diabetic neuropathy, and diabetic retinopathy, among others. However, cardiovascular disease as well as neuropathy may have an autoimmune basis, as well. Women with type 1 DM have a 40% higher risk of death as compared to men with type 1 DM.
Urinary tract infection
People with diabetes show an increased rate of urinary tract infection. The reason is bladder dysfunction that is more common in diabetics than in non-diabetics due to diabetic nephropathy. When present, nephropathy can cause a decrease in bladder sensation, which in turn, can cause increased residual urine, a risk factor for urinary tract infections.
Sexual dysfunction in diabetics is often a result of physical factors such as nerve damage and/or poor circulation, and psychological factors such as stress and/or depression caused by the demands of the disease.
The most common sexual issues in diabetic males are problems with erections and ejaculation: "With diabetes, blood vessels supplying the penis’s erectile tissue can get hard and narrow, preventing the adequate blood supply needed for a firm erection. The nerve damage caused by poor blood glucose control can also cause ejaculate to go into the bladder instead of through the penis during ejaculation, called retrograde ejaculation. When this happens, semen leaves the body in the urine." Another cause for erectile dysfunction are the reactive oxygen species created as a result of the disease. Antioxidants can be used to help combat this.
While there is less material on the correlation between diabetes and female sexual dysfunction than male sexual dysfunction, studies have shown there to be a significant prevalence of sexual problems in diabetic women. Common problems include reduced sensation in the genitals, dryness, difficulty/inability to orgasm, pain during sex, and decreased libido. In some cases diabetes has been shown to decrease oestrogen levels in females, which can affect vaginal lubrication.
Oral contraceptives can be taken by diabetics. Sometimes, contraceptive pills can cause a blood sugar imbalance, but this usually can be corrected by a dosage change. As with any medication, side effects should be taken into account and monitored to prevent serious complications with diabetes.
Type 1 diabetes causes an estimated 5–10% of all diabetes cases or 11–22 million worldwide. In 2006 it affected 440,000 children under 14 years of age and was the primary cause of diabetes in those less than 10 years of age. The incidence of type 1 diabetes has been increasing by about 3% per year.
Rates vary widely by country. In Finland, the incidence is a high of 57 per 100,000 per year, in Japan and China a low of 1 to 3 per 100,000 per year, and in Northern Europe and the U.S., an intermediate of 8 to 17 per 100,000 per year.
Type 1 diabetes was described as an autoimmune disease in the 1970s, based on observations that autoantibodies against islets were discovered in diabetics with other autoimmune deficiencies. It was also shown in the 1980s that immunosuppressive therapies could slow disease progression, further supporting the idea that type 1 diabetes is an autoimmune disorder. The name juvenile diabetes was used earlier as it often first is diagnosed in childhood.
Society and culture
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 person with diabetes) in the U.S.
Funding for research into type 1 diabetes originates from government, industry (e.g., pharmaceutical companies), and charitable organizations. Government funding in the United States is distributed via the National Institute of Health, and in the UK via the National Institute for Health Research or the Medical Research Council. JDRF, originally founded by parents of children with type 1 diabetes, is the world's largest provider of charity based funding for type 1 diabetes research. Other charities include the American Diabetes Association, Diabetes UK, Diabetes Research and Wellness Foundation, Diabetes Australia, the Canadian Diabetes Association.
Pluripotent stem cells can be used to generate beta cells but previously these cells did not function as well as normal beta cells. In 2014 more mature beta cells were produced which released insulin in response to blood sugar when transplanted into mice. Before these techniques can be used in humans more evidence of safety and effectiveness is needed.
Vaccines to treat of prevent Type 1 diabetes are designed to induce immune tolerance to insulin or pancreatic beta cells. While Phase II clinical trials of a vaccine containing alum and recombinant GAD65, an autoantigen involved in type 1 diabetes, were promising, as of 2014 Phase III had failed. As of 2014, other approaches, such as a DNA vaccine encoding proinsulin and a peptide fragment of insulin, were in early clinical development.
Insulin-dependent diabetes characterized by dramatic and recurrent swings in glucose levels, often occurring for no apparent reason, is sometimes known as brittle diabetes, unstable diabetes or labile diabetes, although some experts say the "brittle diabetes" concept "has no biologic basis and should not be used". The results of such swings can be irregular and unpredictable hyperglycemias, frequently involving ketosis, and sometimes serious hypoglycemias. Brittle diabetes occurs no more frequently than in 1% to 2% of diabetics. An insulin pump may be recommended for brittle diabetes to reduce the number of hypoglycemic episodes and better control the morning rise of blood sugar due to the dawn phenomenon. In a small study, 10 of 20 brittle diabetic patients aged 18–23 years who could be traced had died within 22 years, and the remainder, though suffering high rates of complications, were no longer brittle. These results were similar to those of an earlier study by the same authors which found a 19% mortality in 26 patients after 10.5 years.
Because labile diabetes is defined as "episodes of hypoglycemia or hyperglycemia that, whatever their cause, constantly disrupt a patient's life", it can have many causes, some of which include:
- errors in diabetes management, which can include too much insulin being given, in ratio, to carbohydrate being consumed
- interactions with other medical conditions
- psychological problems
- biological factors that interfere with how insulin is processed within the body
- hypoglycemia and hyperglycemia due to strenuous exercise; however, hypoglycemia is more frequent
- insulin exposed to higher temperatures that reduces effectiveness of the insulin hormone in the body
- spontaneous production of insulin in the body due to activity in the beta cells during the period shortly after diagnosis of type 1 diabetes
Exercise related hyperglycemia is caused when hormones (such as adrenaline and cortisol) are released during moderate to strenuous exercise. This happens when the muscles signal the liver to release glucose into the bloodstream by converting stored glycogen into glucose. The cause of exercise related hypoglycemia, on the other hand, occurs when the muscle group being exercised uses up glucose faster than it can be replenished by the body.
One of these biological factors is the production of insulin autoantibodies. High antibody titers can cause episodes of hyperglycemia by neutralizing the insulin, cause clinical insulin resistance requiring doses of over 200 IU/day. However, antibodies may also fail to buffer the release of the injected insulin into the bloodstream after subcutaneous injection, resulting in episodes of hypoglycemia. In some cases, changing the type of insulin administered can resolve this problem. There have been a number of reports that insulin autoantibodies can act as a "sink" for insulin and affect the time to peak, half-life, distribution space, and metabolic clearance, though in most patients these effects are small.
- "Diabetes Blue Circle Symbol". International Diabetes Federation. 17 March 2006.
- "Type 1 Diabetes Mellitus". Retrieved 4 August 2008.
- 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.
- "Diabetes Fact sheet N°312". WHO. October 2013. Retrieved 25 March 2014.
- "Type 1 Diabetes". American Diabetes Association. American Diabetes Association. Retrieved 26 October 2014.
- "What is Type 1 diabetes?". Diabetes UK. Retrieved 25 March 2015.
- Chiang, J. L.; Kirkman, M. S.; Laffel, L. M. B.; Peters, A. L. (16 June 2014). "Type 1 Diabetes Through the Life Span: A Position Statement of the American Diabetes Association". Diabetes Care 37 (7): 2034–2054. doi:10.2337/dc14-1140.
- "FAST FACTS Data and Statistics about Diabetes" (PDF). professional.diabetes.org/facts. American Diabetes Association. Retrieved 25 July 2014.
- Kasper, Dennis L; Braunwald, Eugene; Fauci, Anthony et al. (2005). Harrison's Principles of Internal Medicine (16th ed.). New York: McGraw-Hill. ISBN 0-07-139140-1.
- "webmd Symptoms Type I Diabetes".
- Roy T, Lloyd CE (2012). "Epidemiology of depression and diabetes: a systematic review". J Affect Disord. 142 Suppl: S8–21. doi:10.1016/S0165-0327(12)70004-6. PMID 23062861.
- Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Akerblom HK (2005). "Environmental Triggers and Determinants of Type 1 Diabetes". Diabetes 54: S125–S136. doi:10.2337/diabetes.54.suppl_2.S125. PMID 16306330.
- Bluestone JA, Herold K, Eisenbarth G (2010). "Genetics, pathogenesis and clinical interventions in type 1 diabetes". Nature 464 (7293): 1293–1300. Bibcode:2010Natur.464.1293B. doi:10.1038/nature08933. PMID 20432533.
- Genetics & Diabetes, Diabetes Information. Dr. Warram. Joslin Diabetes Center and Joslin Clinic
- "OMIM Entry – %222100 – DIABETES MELLITUS, INSULIN-DEPENDENT; IDDM". Ncbi.nlm.nih.gov. Retrieved 29 November 2011.
- Fairweather D, Rose NR (2002). "Type 1 diabetes: virus infection or autoimmune disease?". Nat. Immunol. 3 (4): 338–40. doi:10.1038/ni0402-338. PMID 11919574.
- Donner H, Rau H, Walfish PG, Braun J, Siegmund T, Finke R, Herwig J, Usadel KH, Badenhoop K (1997). "CTLA4 alanine-17 confers genetic susceptibility to Graves' disease and to type 1 diabetes mellitus". J. Clin. Endocrinol. Metab. 82 (1): 143–6. doi:10.1210/jcem.82.1.3699. PMID 8989248.
- Chatzigeorgiou A, Harokopos V, Mylona-Karagianni C, Tsouvalas E, Aidinis V, Kamper EF (September 2010). "The pattern of inflammatory/anti-inflammatory cytokines and chemokines in type 1 diabetic patients over time". Ann. Med. 42 (6): 426–38. doi:10.3109/07853890.2010.495951. PMID 20568978.
- Aly H, Gottlieb P (Aug 2009). "The honeymoon phase: intersection of metabolism and immunology.". Current opinion in endocrinology, diabetes, and obesity 16 (4): 286–92. doi:10.1097/med.0b013e32832e0693. PMID 19506474.
- Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation (PDF). Geneva: World Health Organization. 2006. p. 21. ISBN 978-92-4-159493-6.
- Vijan, S (March 2010). "Type 2 diabetes". Annals of Internal Medicine 152 (5): ITC31-15. doi:10.1059/0003-4819-152-5-201003020-01003. PMID 20194231.
- World Health Organisation Department of Noncommunicable Disease Surveillance (1999). "Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications" (PDF).
- ""Diabetes Care" January 2010". American Diabetes Association. Retrieved 29 January 2010.
- 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.
- 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. Retrieved 20 July 2008.
- "Diabetes". World Health Organization. Retrieved 24 January 2011.
- "''Tolerx, Inc. and GlaxoSmithKline (GSK) Announce Phase 3 Defend-1 Study of Otelixizumab in Type 1 Diabetes Did Not Meet Its Primary Endpoint''". Biospace. Retrieved 29 November 2011.
- "Macrogenics press release: ''MacroGenics and Lilly Announce Pivotal Clinical Trial of Teplizumab Did Not Meet Primary Efficacy Endpoint''". Macrogenics.com. 20 October 2010. Retrieved 29 November 2011.
- Borch-Johnsen K, Joner G, Mandrup-Poulsen T, Christy M, Zachau-Christiansen B, Kastrup K, Nerup J (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.
- Shehadeh N, Shamir R, Berant M, Etzioni A (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.
- 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.
- 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.
- 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.19188.8.131.521. PMID 8961125.
- "Stress". www.diabetes.org. American Diabetes Association. Retrieved 11 November 2014.
- Wright JR (2002). "From ugly fish to conquer death: J J R Macleod's fish insulin research, 1922-24". Lancet 359 (9313): 1238–42. doi:10.1016/S0140-6736(02)08222-3. PMID 11955558.
- Rosenbloom AL, Hanas R (1996). "Diabetic ketoacidosis (DKA): treatment guidelines" (PDF). Clin Pediatr (Phila) 35 (5): 261–6. doi:10.1177/000992289603500506. PMID 8804545.
- American Diabetes Association Clinical Guidelines, 2010.
- Jennifer L. Larsen. "Pancreas Transplantation: Indications and Consequences". Edrv.endojournals.org. Retrieved 29 November 2011.
- Bruni, A; Gala-Lopez, B; Pepper, AR; Abualhassan, NS; Shapiro, AJ (2014). "Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges.". Diabetes, metabolic syndrome and obesity : targets and therapy 7: 211–23. doi:10.2147/DMSO.S50789. PMID 25018643.
- Devaraj S, Glaser N, Griffen S, Wang-Polagruto J, Miguelino E, Jialal I (March 2006). "Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes". Diabetes 55 (3): 774–9. doi:10.2337/diabetes.55.03.06.db05-1417. PMID 16505242.
- Granberg V, Ejskjaer N, Peakman M, Sundkvist G (2005). "Autoantibodies to autonomic nerves associated with cardiac and peripheral autonomic neuropathy". Diabetes Care 28 (8): 1959–64. doi:10.2337/diacare.28.8.1959. PMID 16043739.
- Huxley, Rachel R; Peters, Sanne A E; Mishra, Gita D; Woodward, Mark (February 2015). "Risk of all-cause mortality and vascular events in women versus men with type 1 diabetes: a systematic review and meta-analysis". The Lancet Diabetes & Endocrinology. doi:10.1016/S2213-8587(14)70248-7.
- Chen, Hsin-Chui; Su, Li-Ting; Linn, Shin-Zong; Sung, Fung-Chang; Ko, Ming-Chung; Li, Chung-Yi (January 2012). "Increased Risk of Urinary Tract Calculi Among Patients With Diabetes Mellitus–A Population-Based Cohort Study". Urology 79 (1): 86. doi:10.1016/j.urology.2011.07.1431. Retrieved 28 November 2014.
- James, R; Hijaz, A (October 2014). "Lower urinary tract symptoms in women with diabetes mellitus: a current review.". Current urology reports 15 (10): 440. doi:10.1007/s11934-014-0440-3. PMID 25118849.
- McCoy, Krisha. "Sexual Issues and Type 1 Diabetes". everyday Health. Everyday Health Media, LLC. Retrieved 28 November 2014.
- "Sexual Dysfunction in Women". Diabetes.co.uk. Diabetes Digital Media Ltd. Retrieved 28 November 2014.
- Goswami, Sumanta; Vishwanath, Manikanta; Gangadarappa, Suma; Razdan, Rema; Inamdar, Mohammed (Jul–Sep 2014). "Efficacy of ellagic acid and sildenafil in diabetes-induced sexual dysfunction". Pharmacognosy Magazine 10 (39): 581. doi:10.4103/0973-1296.139790. Retrieved 30 November 2014.
- Daneman D (11 March 2006). "Type 1 diabetes". Lancet 367 (9513): 847–58. doi:10.1016/S0140-6736(06)68341-4. PMID 16530579.
- Aanstoot HJ, Anderson BJ, Daneman D, Danne T, Donaghue K, Kaufman F, Réa RR, Uchigata Y (October 2007). "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.
- Soltesz G, Patterson CC, Dahlquist G (October 2007). "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.
- Bottazzo, GF; Florin-Christensen, A; Doniach, D (Nov 30, 1974). "Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies.". Lancet 2 (7892): 1279–83. doi:10.1016/s0140-6736(74)90140-8. PMID 4139522.
- Herold, KC; Vignali, DA; Cooke, A; Bluestone, JA (Apr 2013). "Type 1 diabetes: translating mechanistic observations into effective clinical outcomes.". Nature reviews. Immunology 13 (4): 243–56. doi:10.1038/nri3422. PMID 23524461.
- Johnson, Linda (18 November 2008). "Study: Cost of diabetes $218B". USA Today. Associated Press.
- Diabetes Research and Wellness Foundation
- Minami, K; Seino, S (18 March 2013). "Current status of regeneration of pancreatic β-cells.". Journal of diabetes investigation 4 (2): 131–41. doi:10.1111/jdi.12062. PMID 24843642.
- Pagliuca, FW; Millman, JR; Gürtler, M; Segel, M; Van Dervort, A; Ryu, JH; Peterson, QP; Greiner, D; Melton, DA (9 October 2014). "Generation of functional human pancreatic β cells in vitro.". Cell 159 (2): 428–39. doi:10.1016/j.cell.2014.09.040. PMID 25303535.
- Rezania, A; Bruin, JE; Arora, P; Rubin, A; Batushansky, I; Asadi, A; O'Dwyer, S; Quiskamp, N; Mojibian, M; Albrecht, T; Yang, YH; Johnson, JD; Kieffer, TJ (November 2014). "Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells.". Nature Biotechnology 32 (11): 1121–33. doi:10.1038/nbt.3033. PMID 25211370.
- Lernmark A, Larsson HE. Immune therapy in type 1 diabetes mellitus. Nat Rev Endocrinol. 2013 Feb;9(2):92-103. Review PMID 23296174
- "Diabetes Mellitus (DM): Diabetes Mellitus and Disorders of Carbohydrate Metabolism: Merck Manual Professional". Merck.com. Retrieved 30 July 2010.
- Dorner M, Pinget M, Brogard JM (May 1977). "[Essential labile diabetes (author's transl)]". MMW Munch Med Wochenschr 119 (19): 671–4. PMID 406527.
- Higuchi, Chigusa; Tone, Atsuhito; Iseda, Izumi; Tsukamoto, Keiko; Katayama, Akihiro (2010). "A Pregnant Patient with Brittle Type 1 Diabetes Successfully Managed by CSII Therapy with Insulin Aspart". Journal of Diabetes & Metabolism 01. doi:10.4172/2155-6156.1000104.
- Cartwright A, Wallymahmed M, Macfarlane IA, Wallymahmed A, Williams G, Gill GV (2011). "The outcome of brittle type 1 diabetes--a 20 year study". QJM 104 (7): 575–9. doi:10.1093/qjmed/hcr010. PMID 21285231.
- Kent LA, Gill GV, Williams G (September 1994). "Mortality and outcome of patients with brittle diabetes and recurrent ketoacidosis". Lancet 344 (8925): 778–81. doi:10.1016/S0140-6736(94)92340-X. PMID 7916072.
- Davidson MB, Kumar D, Smith W (1991). "Successful treatment of unusual case of brittle diabetes with sulfated beef insulin". Diabetes Care 14 (11): 1109–10. doi:10.2337/diacare.14.1.1109b. PMID 1797500.
- Fineberg SE, Kawabata TT, Finco-Kent D, Fountaine RJ, Finch GL, Krasner AS (2007). "Immunological Responses to Exogenous Insulin". Endocrine Reviews 28 (6): 625–52. doi:10.1210/er.2007-0002. PMID 17785428.
- Diabetes mellitus type 1 at DMOZ
- Kids and Teens: Type 1 Diabetes at DMOZ
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) – Diabetes in America Textbook (PDFs)
- IDF Diabetes Atlas
- International Diabetes Federation
- type 1 Diabetes at the American Diabetes Association
- National Diabetes Information Clearinghouse