Type 1 diabetes
|Type 1 diabetes|
|Other names||Diabetes mellitus type 1, insulin-dependent diabetes, juvenile diabetes|
|A blue circle, the symbol for diabetes.|
|Symptoms||Frequent urination, increased thirst, increased hunger, weight loss|
|Complications||Diabetic ketoacidosis, nonketotic hyperosmolar coma, poor healing, cardiovascular disease, damage to the eyes|
|Usual onset||Relatively short period of time|
|Causes||Body does not produce enough insulin|
|Risk factors||Family history, celiac disease|
|Diagnostic method||Blood sugar, A1C|
|Treatment||Insulin, diabetic diet, exercise|
|Frequency||~7.5% of diabetes cases|
Type 1 diabetes (T1D), previously known as juvenile diabetes, is a form of diabetes in which very little or no insulin is produced by the islets of Langerhans in the pancreas. Insulin is a hormone required for the body to use blood sugar. Before treatment this results in high blood sugar levels in the body. The classic symptoms are frequent urination, increased thirst, increased hunger, and weight loss. Additional symptoms may include blurry vision, tiredness, and poor wound healing. Symptoms typically develop over a short period of time, often a matter of weeks.
The cause of type 1 diabetes is unknown, but it is believed to involve a combination of genetic and environmental factors. Risk factors include having a family member with the condition. The underlying mechanism involves an autoimmune destruction of the insulin producing beta cells in the pancreas. Diabetes is diagnosed by testing the level of sugar or glycated hemoglobin (HbA1C) in the blood. Type 1 diabetes can be distinguished from type 2 by testing for the presence of autoantibodies.
There is no known way to prevent type 1 diabetes. Treatment with insulin is required for survival. Insulin therapy is usually given by injection just under the skin but can also be delivered by an insulin pump. A diabetic diet and exercise are important parts of management. If left untreated, diabetes can cause many complications. Complications of relatively rapid onset include diabetic ketoacidosis and nonketotic hyperosmolar coma. 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 dosing of insulin.
Type 1 diabetes makes up an estimated 5–10% of all diabetes cases. The number of people affected globally is unknown, although it is estimated that about 80,000 children develop the disease each year. Within the United States the number of people affected is estimated at one to three million. Rates of disease vary widely, with approximately 1 new case per 100,000 per year in East Asia and Latin America and around 30 new cases per 100,000 per year in Scandinavia and Kuwait. It typically begins in children and young adults.
Signs and symptoms
Type 1 diabetes is often diagnosed when diabetic ketoacidosis occurs. The signs and symptoms of diabetic ketoacidosis include dry skin, rapid deep breathing, drowsiness, increased thirst, frequent urination, abdominal pain, and vomiting.
Some people with type 1 diabetes experience dramatic and recurrent swings in glucose levels, often occurring for no apparent reason; this is called "unstable diabetes", "labile diabetes" or "brittle diabetes". The results of such swings can be irregular and unpredictable hyperglycemias, sometimes involving ketoacidosis, and sometimes serious hypoglycemias. Brittle diabetes occurs no more frequently than in 1% to 2% of diabetics.
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 exposure to an antigen.
Type 1 diabetes is a disease that involves many genes. The risk of a child developing type 1 diabetes is about 5% if the father has it, about 8% if a sibling has it, and about 3% if the mother has it. If one identical twin is affected there is about a 40% to 50% chance the other will be too. Some studies of heritability have estimated it at 80 to 86%.
More than 50 genes are associated with type 1 diabetes. 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.
There is on the order of a 10-fold difference in occurrence among Caucasians living in different areas of Europe. Environmental triggers and protective factors under research include dietary agents such as proteins in gluten, time of weaning, gut microbiota, viral infections, and bacterial infections like paratuberculosis.
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 diabetes after accidental poisoning. Pyrinuron was withdrawn from the U.S. market in 1979 and it is not approved by the Environmental Protection Agency for use in the U.S. Streptozotocin (Zanosar), an antineoplastic agent, is selectively toxic to the beta cells of the pancreatic islets. It is used in research for inducing type 1 diabetes on rodents and for treating metastatic cancer of the pancreatic islet cells in patients whose cancer cannot be removed by surgery. Other pancreatic problems, including trauma, pancreatitis, or tumors (either malignant or benign) can also lead to loss of insulin production.
Monoclonal antibodies used for the treatment of cancer (checkpoint inhibitors inhibiting PD-1 and PD-L1), especially nivolumab and pembrolizumab have been reported to occasionally induce autoimmune diabetes.
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 a type IV hypersensitivity 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.
Alpha cell dysfunction
Onset of autoimmune diabetes is accompanied by impaired ability to regulate the hormone glucagon, which acts in antagonism with insulin to regulate blood sugar and metabolism. While the causes and mechanisms are still being studied and hypotheses abound, what is clear and agreed upon is that progressive beta cell destruction leads to dysfunction in the neighboring alpha cells which secrete glucagon, exacerbating excursions away from euglycemia in both directions; overproduction of glucagon after meals causes sharper hyperglycemia, and failure to stimulate glucagon upon incipient hypoglycemia prevents a glucagon-mediated rescue of glucose levels.
Onset of type 1 diabetes is followed by an increase in glucagon secretion after meals. Increases have been measured up to 37% during the first year of diagnosis, while c-peptide levels (indicative of islet-derived insulin), decline by up to 45%. Insulin production will continue to fall as the immune system follows its course of progressive beta cell destruction, and islet-derived insulin will continue to be replaced by therapeutic exogenous insulin. Simultaneously, there is measurable alpha cell hypertrophy and hyperplasia in the early overt stage of the disease, leading to expanded alpha cell mass. This, together with failing beta cell insulin secretion, begins to account for rising glucagon levels that contribute to hyperglycemia. Some researchers believe glucagon dysregulation to be the primary cause of early stage hyperglycemia. Leading hypotheses for the cause of postprandial hyperglucagonemia suggest that exogenous insulin therapy is inadequate to replace the lost intraislet signalling to alpha cells previously mediated by beta cell-derived pulsatile insulin secretion. Under this working hypothesis intensive insulin therapy has attempted to mimic natural insulin secretion profiles in exogenous insulin infusion therapies.
Hypoglycemic glucagon impairment
Hypoglycemia in type 1 diabetics is often a result of over-administered insulin therapy, though being in a fasting state, exercising without proper adjustment of insulin, sleep, and alcohol can also contribute. The normal counter regulatory responses to hypoglycemia are impaired in type 1 diabetics. Glucagon secretion is normally increased upon falling glucose levels, but normal glucagon response to hypoglycemia is blunted when measured in type 1 diabetics and compared to healthy individuals experiencing an equal insulin-induced hypoglycemic trigger. Beta cell glucose sensing and subsequent suppression of administered insulin secretion is absent, leading to islet hyperinsulinemia which inhibits glucagon release.
Autonomic inputs to alpha cells are much more important for glucagon stimulation in the moderate to severe ranges of hypoglycemia, yet the autonomic response is blunted in a number of ways. Recurrent hypoglycemia leads to metabolic adjustments in the glucose sensing areas of the brain, shifting the threshold for counter regulatory activation of the sympathetic nervous system to lower glucose concentration. This is known as hypoglycemic unawareness. Subsequent hypoglycemia is met with impairment in sending of counter regulatory signals to the islets and adrenal cortex. This accounts for the lack of glucagon stimulation and epinephrine release that would normally stimulate and enhance glucose release and production from the liver, rescuing the diabetic from severe hypoglycemia, coma, and death. Numerous hypotheses have been produced in the search for a cellular mechanism of hypoglycemic unawareness, and a consensus has yet to be reached. The major hypotheses are summarized in the following table: 
|Mechanisms of hypoglycemic unawareness|
|Glycogen supercompensation||Increased glycogen stores in astrocytes might contribute supplementary glycosyl units for metabolism, counteracting the central nervous system perception of hypoglycemia.|
|Enhanced glucose metabolism||Altered glucose transport and enhanced metabolic efficiency upon recurring hypoglycemia relieves oxidative stress that would activate sympathetic response.|
|Alternative fuel hypothesis||Decreased reliance on glucose, supplementation of lactate from astrocytes, or ketones meet metabolic demands and reduce stress to brain.|
|Brain neuronal communication||Hypothalamic inhibitory GABA normally decreases during hypoglycemia, disinhibiting signals for sympathetic tone. Recurrent episodes of hypoglycemia result in increased basal GABA which fails to decrease normally during subsequent hypoglycemia. Inhibitory tone remains and sympathetic tone is not increased.|
In addition, autoimmune diabetes is characterized by a loss of islet specific sympathetic innervation. This loss constitutes an 80-90% reduction of islet sympathetic nerve endings, happens early in the progression of the disease, and is persistent though the life of the patient. It is linked to the autoimmune aspect of type 1 diabetics and fails to occur in type 2 diabetics. Early in the autoimmune event, the axon pruning is activated in islet sympathetic nerves. Increased BDNF and ROS that result from insulitis and beta cell death stimulate the p75 neurotrophin receptor (p75NTR), which acts to prune off axons. Axons are normally protected from pruning by activation of tropomyosin receptor kinase A (Trk A) receptors by NGF, which in islets is primarily produced by beta cells. Progressive autoimmune beta cell destruction therefore causes both the activation of pruning factors and the loss of protective factors to the islet sympathetic nerves. This unique form of neuropathy is a hallmark of type 1 diabetes, and plays a part in the loss of glucagon rescue of severe hypoglycemia.
|Condition||2-hour glucose||Fasting glucose||HbA1c|
|Normal||< 7.8||< 140||< 6.1||< 110||< 42||< 6.0|
|Impaired fasting glycaemia||< 7.8||< 140||6.1–7.0||110–125||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 unexplained 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 (low blood sugar).
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.
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 and early introduction of gluten-containing cereals in the diet increases the risk of developing islet cell autoantibodies; various other nutritional risk factors are being studied, but no firm evidence has been found. Giving children 2000 IU of vitamin D daily 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 niacinamide (vitamin B3), 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.
People with type 1 diabetes and undiagnosed celiac disease have worse glycaemic control and a higher prevalence of nephropathy and retinopathy. Gluten-free diet, when performed strictly, improves diabetes symptoms and appears to have a protective effect against developing long-term complications. Nevertheless, dietary management of both these diseases is challenging and these patients have poor compliance of the diet.
Diabetes is often managed by a number of health care providers including a dietitian, nurse educator, eye doctor, endocrinologist, and podiatrist.
There is limited evidence for the usefulness of routine use of low-carbohydrate dieting for people with type 1 diabetes. Although for certain individuals it may be feasible to follow a low-carbohydrate regime combined with carefully managed insulin dosing, this is hard to maintain and there are concerns about possible adverse health effects caused by the diet. In general, people with type 1 diabetes are advised to follow an individualized eating plan rather than a pre-decided one.
There are camps for children to teach them how and when to use or monitor their insulin without parental help. 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.
Injections of insulin – via subcutaneous injection using either a syringe or using an insulin pump – are necessary for those living with type 1 diabetes because it cannot be treated by diet and exercise alone. Insulin dosage is adjusted taking into account food intake, blood glucose levels and physical activity.
Untreated type 1 diabetes can commonly lead to diabetic ketoacidosis which can result in death. Diabetic ketoacidosis can cause cerebral edema (accumulation of liquid in the brain). This is a life-threatening issue and children are at a higher risk for cerebral edema than adults, causing ketoacidosis to be 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%.
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 one to two hours with peak action of four to 10 hours. Long-acting insulin is usually given at the same time once per day. The action onset is roughly 1 to 2 hours with a sustained action of up to 24 hours. Some insulins are biosynthetic products produced using genetic recombination techniques; formerly, cattle or pig insulins were used, and even sometimes insulin from fish.
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. Symptoms include excess sweating, excessive hunger, fainting, fatigue, lightheadedness and shakiness. 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 continuous glucose monitors still have a margin of error.
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, which 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.
Islet cell transplantation
Islet cell transplantation may be an option for some people with type 1 diabetes that is not well controlled with insulin. Difficulties include finding donors that are 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 following the procedure, occurred in 44% of people on registry from 2010. In the United States, as of 2016, it is considered an experimental treatment.
Complications of poorly managed type 1 diabetes 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. The life expectancy of an individual with type 1 diabetes is 11 years less for men and 13 years less for women. People with type 1 diabetes are higher risk for other autoimmune diseases, such as autoimmune thyroid disease, celiac disease, rheumatoid arthritis, and lupus.
About 12 percent of people with type 1 diabetes have clinical depression. About 6 percent of people with type 1 diabetes also have celiac disease, but in most cases there are no digestive symptoms or are mistakenly attributed to poor control of diabetes, gastroparesis or diabetic neuropathy. In most cases, celiac disease is diagnosed after onset of type 1 diabetes. The association of celiac disease with type 1 diabetes increases the risk of complications, such as retinopathy and mortality. This association can be explained by shared genetic factors, and inflammation or nutritional deficiencies caused by untreated celiac disease, even if type 1 diabetes is diagnosed first.
Urinary tract infection
People with diabetes show an increased rate of urinary tract infection. The reason is bladder dysfunction is more common in people with diabetes than people without diabetes due to diabetes 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 people with diabetes is often a result of physical factors such as nerve damage and poor circulation, and psychological factors such as stress and/or depression caused by the demands of the disease.
The most common sexual issues in males with diabetes 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 of erectile dysfunction is reactive oxygen species created as a result of the disease. Antioxidants can be used to help combat this.
Sexual problems are common in women who have diabetes, including reduced sensation in the genitals, dryness, difficulty/inability to orgasm, pain during sex, and decreased libido. Diabetes sometimes decreases estrogen levels in females, which can affect vaginal lubrication. Less is known about the correlation between diabetes and sexual dysfunction in females than in males.
Women with type 1 diabetes show a higher than normal rate of polycystic ovarian syndrome (PCOS). The reason may be that the ovaries are exposed to high insulin concentrations since women with type 1 diabetes can have frequent hyperglycemia.
Type 1 diabetes makes up 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.
In the United States, type 1 and 2 diabetes affected about 208,000 youths under the age of 20 in 2015. Over 18,000 youths are diagnosed with Type 1 diabetes every year. Every year about 234,051 Americans die due to diabetes (type I or II) or diabetes-related complications, with 69,071 having it as the primary cause of death.
In Australia, about one million people have been diagnosed with diabetes and of this figure 130,000 people have been diagnosed with type 1 diabetes. Australia ranks 6th-highest in the world with children under 14 years of age. Between 2000 and 2013, 31,895 new cases were established, with 2,323 in 2013, a rate of 10–13 cases per 100,00 people each year. Aboriginals and Torres Strait Islander people are less affected.
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
Type 1 and 2 diabetes 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. In the United States $245 billion every year is attributed to diabetes. Individuals diagnosed with diabetes have 2.3 times the health care costs as individuals who do not have diabetes. One in ten health care dollars are spent on individuals with type 1 and 2 diabetes.
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. The Juvenile Diabetes Research Foundation (JDRF), 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.
A number of approaches have been explored to understand causes and provide treatments for type 1.
Data suggest that gliadin (a protein present in gluten) might play a role in the development of type 1 diabetes, but the mechanism is not fully understood. Increased intestinal permeability caused by gluten and the subsequent loss of intestinal barrier function, which allows the passage of pro-inflammatory substances into the blood, may induce the autoimmune response in genetically predisposed individuals to type 1 diabetes. There is evidence from experiments conducted in animal models that removal of gluten from the diet may prevent the onset of type 1 diabetes but there has been conflicting research in humans.
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. Several viruses have been implicated, including enteroviruses (especially coxsackievirus B), cytomegalovirus, Epstein–Barr virus, mumps virus, rubella virus and rotavirus, but to date there is no stringent evidence to support this hypothesis in humans. A 2011 systematic review and meta-analysis showed an association between enterovirus infections and type 1 diabetes, but other studies have shown that, rather than triggering an autoimmune process, enterovirus infections, as coxsackievirus B, could protect against onset and development of type 1 diabetes. Some studies have found a decreased risk with oral rotavirus vaccine while others found no effect.
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 are being looked at to treat or prevent type 1 diabetes by inducing 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. The rotavirus vaccine and BCG vaccine are associated with a lower risk of type 1 diabetes. Research continues to look at the BCG vaccine in type 1 diabetes as of 2019[update].
- "Causes of Diabetes". NIDDK. August 2014. Archived from the original on 10 August 2016. Retrieved 31 July 2016.
- "Types of Diabetes". NIDDK. February 2014. Archived from the original on 16 August 2016. Retrieved 31 July 2016.
- "Diabetes Blue Circle Symbol". International Diabetes Federation. 17 March 2006. Archived from the original on 5 August 2007.
- "Diabetes Fact sheet N°312". WHO. November 2016. Archived from the original on 26 August 2013. Retrieved 29 May 2017.
- Chiang JL, Kirkman MS, Laffel LM, Peters AL (July 2014). "Type 1 diabetes through the life span: a position statement of the American Diabetes Association". Diabetes Care. 37 (7): 2034–54. doi:10.2337/dc14-1140. PMC 5865481. PMID 24935775.
- Elfström P, Sundström J, Ludvigsson JF (November 2014). "Systematic review with meta-analysis: associations between coeliac disease and type 1 diabetes". Alimentary Pharmacology & Therapeutics. 40 (10): 1123–32. doi:10.1111/apt.12973. PMID 25270960. S2CID 25468009.
- "Diagnosis of Diabetes and Prediabetes". NIDDK. May 2015. Archived from the original on 16 August 2016. Retrieved 31 July 2016.
- Daneman D (March 2006). "Type 1 diabetes". Lancet. 367 (9513): 847–58. doi:10.1016/S0140-6736(06)68341-4. PMID 16530579. S2CID 21485081.
- Torpy, JM (September 2007). "Type 1 Diabetes". JAMA. 298 (12): 1472. doi:10.1001/jama.298.12.1472. PMID 17895465.
- "Alternative Devices for Taking Insulin". NIDDK. July 2016. Archived from the original on 16 August 2016. Retrieved 31 July 2016.
- "Fast Facts Data and Statistics about Diabetes". American Diabetes Association. Archived from the original on 16 December 2015. Retrieved 25 July 2014.
- Global report on diabetes (PDF). World Health Organization. 2016. pp. 26–27. ISBN 978-92-4-156525-7. Archived (PDF) from the original on 7 October 2016. Retrieved 31 July 2016.
- Skyler, Jay (2012). Atlas of diabetes (4th ed.). New York: Springer. pp. 67–68. ISBN 978-1-4614-1028-7. Archived from the original on 8 September 2017.
- Uspal NG, Schapiro ES (February 2011). "Cataracts as the initial manifestation of type 1 diabetes mellitus". Pediatric Emergency Care. 27 (2): 132–4. doi:10.1097/pec.0b013e318209bf0a. PMID 21293223.
- "webmd Symptoms Type I Diabetes". Archived from the original on 23 June 2013.
- "Diabetes Mellitus (DM): Diabetes Mellitus and Disorders of Carbohydrate Metabolism: Merck Manual Professional". Merck.com. February 2017.
- Khan Mohammad Beigi P (2018). "Alopecia Areata". Springer International Publishing. pp. 39–54. doi:10.1007/978-3-319-72134-7_8. ISBN 9783319721330. Missing or empty
- Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Akerblom HK (December 2005). "Environmental triggers and determinants of type 1 diabetes". Diabetes. 54 Suppl 2: S125–36. doi:10.2337/diabetes.54.suppl_2.S125. PMID 16306330.
- Pociot F, Lernmark Å (June 2016). "Genetic risk factors for type 1 diabetes". Lancet. 387 (10035): 2331–2339. doi:10.1016/s0140-6736(16)30582-7. PMID 27302272. S2CID 205982020.
- Owen, Katharine (2014). Oxford Handbook of Endocrinology and Diabetes. Oxford University Press. p. 690. ISBN 9780199644438. Archived from the original on 8 September 2017.
- "OMIM Entry – %222100 – Diabetes Mellitus, Insulin-dependentT". IDDM Ncbi.nlm.nih.gov. Archived from the original on 8 August 2010. Retrieved 29 November 2011.
- Tomita, T (20 August 2017). "Apoptosis of pancreatic β-cells in Type 1 diabetes". Bosnian Journal of Basic Medical Sciences. 17 (3): 183–193. doi:10.17305/bjbms.2017.1961. PMC 5581966. PMID 28368239.
- Narayan KM, Williams D, Gregg EW, Cowie CC (2010). Diabetes Public Health: From Data to Policy. Oxford University Press. p. 671. ISBN 9780199749140. Archived from the original on 8 September 2017.
- Melmed S, Polonsky KS, Larsen PR, Kronenberg H (2015). Williams Textbook of Endocrinology. Elsevier Health Sciences. p. 50. ISBN 9780323297387. Archived from the original on 8 September 2017.
- Bluestone JA, Herold K, Eisenbarth G (April 2010). "Genetics, pathogenesis and clinical interventions in type 1 diabetes". Nature. 464 (7293): 1293–300. Bibcode:2010Natur.464.1293B. doi:10.1038/nature08933. PMC 4959889. PMID 20432533.
- Serena G, Camhi S, Sturgeon C, Yan S, Fasano A (August 2015). "The Role of Gluten in Celiac Disease and Type 1 Diabetes". Nutrients. 7 (9): 7143–62. doi:10.3390/nu7095329. PMC 4586524. PMID 26343710.
- Bibbò S, Dore MP, Pes GM, Delitala G, Delitala AP (February 2017). "Is there a role for gut microbiota in type 1 diabetes pathogenesis?". Annals of Medicine. 49 (1): 11–22. doi:10.1080/07853890.2016.1222449. PMID 27499366. S2CID 21656176.
- Rewers M, Ludvigsson J (June 2016). "Environmental risk factors for type 1 diabetes". Lancet (Review). 387 (10035): 2340–2348. doi:10.1016/S0140-6736(16)30507-4. PMC 5571740. PMID 27302273.
- World Health Organization Department of Noncommunicable Disease Surveillance (2019). "Classification of diabetes mellitus". Retrieved 30 September 2020.
Particular viruses have been associated with β-cell destruction and have been implicated in inducing or triggering T1DM, but their role in its aetiology has remained uncertain. Diabetes occurs in some people with congenital rubella. In addition, Coxsackie B and viruses such as cytomegalovirus, adenovirus and mumps have been implicated in inducing T1DM
- Gill CO, Saucier L, Meadus WJ (March 2011). "Mycobacterium avium subsp. paratuberculosis in dairy products, meat, and drinking water". Journal of Food Protection. 74 (3): 480–99. doi:10.4315/0362-028X.JFP-10-301. PMID 21375889.
- Thayer KA, Heindel JJ, Bucher JR, Gallo MA (June 2012). "Role of environmental chemicals in diabetes and obesity: a National Toxicology Program workshop review". Environmental Health Perspectives (Review). 120 (6): 779–89. doi:10.1289/ehp.1104597. PMC 3385443. PMID 22296744.
- "Pyriminil". U.S. National Library of Medicine. Archived from the original on 4 July 2013.
- Wu J, Yan LJ (April 2015). "Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity". Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy (Review). 8: 181–8. doi:10.2147/DMSO.S82272. PMC 4396517. PMID 25897251.
- Brentjens R, Saltz L (June 2001). "Islet cell tumors of the pancreas: the medical oncologist's perspective". The Surgical Clinics of North America (Review). 81 (3): 527–42. doi:10.1016/S0039-6109(05)70141-9. PMID 11459269.
- de Filette, Jeroen; Andreescu, Corina; Cools, Filip; Bravenboer, Bert; Velkeniers, Brigitte (12 March 2019). "A systematic review and meta-analysis of endocrine-related adverse events associated with immune checkpoint inhibitors". Hormone and Metabolic Research. 51 (3): 145–156. doi:10.1055/a-0843-3366. PMID 30861560.
- 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". Annals of Medicine. 42 (6): 426–38. doi:10.3109/07853890.2010.495951. PMID 20568978. S2CID 10243765.
- Aly H, Gottlieb P (August 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. S2CID 5242656.
- Farhy LS, McCall AL (July 2015). "Glucagon - the new 'insulin' in the pathophysiology of diabetes". Current Opinion in Clinical Nutrition and Metabolic Care. 18 (4): 407–14. doi:10.1097/mco.0000000000000192. PMID 26049639. S2CID 19872862.
- Yosten GL (February 2018). "Alpha cell dysfunction in type 1 diabetes". Peptides. 100: 54–60. doi:10.1016/j.peptides.2017.12.001. PMID 29412832. S2CID 46878644.
- Brown RJ, Sinaii N, Rother KI (July 2008). "Too much glucagon, too little insulin: time course of pancreatic islet dysfunction in new-onset type 1 diabetes". Diabetes Care. 31 (7): 1403–4. doi:10.2337/dc08-0575. PMC 2453684. PMID 18594062.
- Unger RH, Cherrington AD (January 2012). "Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover". The Journal of Clinical Investigation. 122 (1): 4–12. doi:10.1172/JCI60016. PMC 3248306. PMID 22214853.
- Meier JJ, Kjems LL, Veldhuis JD, Lefèbvre P, Butler PC (April 2006). "Postprandial suppression of glucagon secretion depends on intact pulsatile insulin secretion: further evidence for the intraislet insulin hypothesis". Diabetes. 55 (4): 1051–6. doi:10.2337/diabetes.55.04.06.db05-1449. PMID 16567528.
- Cooperberg BA, Cryer PE (December 2009). "Beta-cell-mediated signaling predominates over direct alpha-cell signaling in the regulation of glucagon secretion in humans". Diabetes Care. 32 (12): 2275–80. doi:10.2337/dc09-0798. PMC 2782990. PMID 19729529.
- Paolisso G, Sgambato S, Torella R, Varricchio M, Scheen A, D'Onofrio F, Lefèbvre PJ (June 1988). "Pulsatile insulin delivery is more efficient than continuous infusion in modulating islet cell function in normal subjects and patients with type 1 diabetes". The Journal of Clinical Endocrinology and Metabolism. 66 (6): 1220–6. doi:10.1210/jcem-66-6-1220. PMID 3286673.
- "Diabetic hypoglycemia - Symptoms and causes". Mayo Clinic. Retrieved 23 December 2019.
- Banarer S, McGregor VP, Cryer PE (April 2002). "Intraislet hyperinsulinemia prevents the glucagon response to hypoglycemia despite an intact autonomic response". Diabetes. 51 (4): 958–65. doi:10.2337/diabetes.51.4.958. PMID 11916913.
- Raju B, Cryer PE (March 2005). "Loss of the decrement in intraislet insulin plausibly explains loss of the glucagon response to hypoglycemia in insulin-deficient diabetes: documentation of the intraislet insulin hypothesis in humans". Diabetes. 54 (3): 757–64. doi:10.2337/diabetes.54.3.757. PMID 15734853.
- Tesfaye N, Seaquist ER (November 2010). "Neuroendocrine responses to hypoglycemia". Annals of the New York Academy of Sciences. 1212 (1): 12–28. Bibcode:2010NYASA1212...12T. doi:10.1111/j.1749-6632.2010.05820.x. PMC 2991551. PMID 21039590.
- Reno CM, Litvin M, Clark AL, Fisher SJ (March 2013). "Defective counterregulation and hypoglycemia unawareness in diabetes: mechanisms and emerging treatments". Endocrinology and Metabolism Clinics of North America. 42 (1): 15–38. doi:10.1016/j.ecl.2012.11.005. PMC 3568263. PMID 23391237.
- Martín-Timón I, Del Cañizo-Gómez FJ (July 2015). "Mechanisms of hypoglycemia unawareness and implications in diabetic patients". World Journal of Diabetes. 6 (7): 912–26. doi:10.4239/wjd.v6.i7.912. PMC 4499525. PMID 26185599.
- Mundinger TO, Taborsky GJ (October 2016). "Early sympathetic islet neuropathy in autoimmune diabetes: lessons learned and opportunities for investigation". Diabetologia. 59 (10): 2058–67. doi:10.1007/s00125-016-4026-0. PMC 6214182. PMID 27342407.
- Mundinger TO, Mei Q, Foulis AK, Fligner CL, Hull RL, Taborsky GJ (August 2016). "Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves". Diabetes. 65 (8): 2322–30. doi:10.2337/db16-0284. PMC 4955989. PMID 27207540.
- 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:10.7326/0003-4819-152-5-201003020-01003. PMID 20194231.
- World Health Organization Department of Noncommunicable Disease Surveillance (1999). "Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications" (PDF). Archived (PDF) from the original on 8 March 2003.
- ""Diabetes Care" January 2010". Diabetes Care. American Diabetes Association. 33: S3. 2010. doi:10.2337/dc10-S003. PMC 2797388. PMID 20042773.
- 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.
- "Diabetes". World Health Organization. Archived from the original on 26 January 2011. 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. Archived from the original on 29 September 2011. 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. Archived from the original on 22 January 2012. 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. S2CID 22513380.
- Shehadeh N, Shamir R, Berant M, Etzioni A (December 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. S2CID 42665454.
- Visser J, Rozing J, Sapone A, Lammers K, Fasano A (May 2009). "Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms". Annals of the New York Academy of Sciences. 1165 (1): 195–205. Bibcode:2009NYASA1165..195V. doi:10.1111/j.1749-6632.2009.04037.x. PMC 2886850. PMID 19538307.
- 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. doi:10.1093/ajcn/78.6.1053. 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. S2CID 16665889.
- 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.19184.108.40.2061. PMID 8961125. S2CID 46135323.
- Hogg-Kollars S, Al Dulaimi D, Tait K, Rostami K (2014). "Type 1 diabetes mellitus and gluten induced disorders". Gastroenterology and Hepatology from Bed to Bench (Review). 7 (4): 189–97. PMC 4185872. PMID 25289132.
- "Your Diabetes Care Team". WebMD. Retrieved 1 November 2017.
- Seckold R, Fisher E, de Bock M, King BR, Smart CE (October 2018). "The ups and downs of low-carbohydrate diets in the management of Type 1 diabetes: a review of clinical outcomes". Diabet. Med. (Review). 36 (3): 326–334. doi:10.1111/dme.13845. PMID 30362180. S2CID 53102654.
Low‐carbohydrate diets are of interest for improving glycaemic outcomes in the management of Type 1 diabetes. There is limited evidence to support their routine use in the management of Type 1 diabetes.
- Ly TT (2015). "Technology and type 1 diabetes: Closed-loop therapies". Current Pediatrics Reports. 3 (2): 170–176. doi:10.1007/s40124-015-0083-y. S2CID 68302123.
- "Stress". www.diabetes.org. American Diabetes Association. Archived from the original on 12 November 2014. Retrieved 11 November 2014.
- Shrivastava SR, Shrivastava PS, Ramasamy J (March 2013). "Role of self-care in management of diabetes mellitus". Journal of Diabetes and Metabolic Disorders. 12 (1): 14. doi:10.1186/2251-6581-12-14. PMC 3599009. PMID 23497559.
- American Diabetes Association (2015). "DKA (ketoacidosis) and ketones". American Diabetes Association. Archived from the original on 29 April 2010.
- Tasker RC, Acerini CL (June 2014). "Cerebral edema in children with diabetic ketoacidosis: vasogenic rather than cellular?". Pediatric Diabetes. 15 (4): 261–70. doi:10.1111/pedi.12153. PMID 24866062. S2CID 6639587.
- American Diabetes Association Clinical Guidelines, 2010.
- "Long-Acting Insulin: How It Works". Healthline. 23 October 2015. Retrieved 10 February 2019.
- Wright JR (April 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. S2CID 26381227.
- "Low Blood Glucose (Hypoglycemia) - NIDDK". nih.gov.
- Pandit K (December 2012). "Continuous glucose monitoring". Indian Journal of Endocrinology and Metabolism. 16 (Suppl 2): S263–6. doi:10.4103/2230-8210.104056 (inactive 10 November 2020). PMC 3603043. PMID 23565395.CS1 maint: DOI inactive as of November 2020 (link)
- Blauw H, Keith-Hynes P, Koops R, DeVries JH (November 2016). "A Review of Safety and Design Requirements of the Artificial Pancreas". Annals of Biomedical Engineering. 44 (11): 3158–3172. doi:10.1007/s10439-016-1679-2. PMC 5093196. PMID 27352278.
- Bekiari E, Kitsios K, Thabit H, Tauschmann M, Athanasiadou E, Karagiannis T, Haidich AB, Hovorka R, Tsapas A (April 2018). "Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis". BMJ. 361: k1310. doi:10.1136/bmj.k1310. PMC 5902803. PMID 29669716.
- Larsen JL (2004). "Pancreas Transplantation: Indications and Consequences". Endocrine Reviews. Edrv.endojournals.org. 25 (6): 919–46. doi:10.1210/er.2002-0036. PMID 15583023. Archived from the original on 15 July 2012. 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. PMC 4075233. PMID 25018643.
- Hatipoglu B (December 2016). "Islet Cell Transplantation and Alternative Therapies". Endocrinology and Metabolism Clinics of North America. 45 (4): 923–931. doi:10.1016/j.ecl.2016.06.004. PMID 27823612.
- 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 (August 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 RR, Peters SA, Mishra GD, Woodward M (March 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. 3 (3): 198–206. doi:10.1016/S2213-8587(14)70248-7. PMID 25660575.
- Livingstone SJ, Levin D, Looker HC, Lindsay RS, Wild SH, Joss N, Leese G, Leslie P, McCrimmon RJ, Metcalfe W, McKnight JA, Morris AD, Pearson DW, Petrie JR, Philip S, Sattar NA, Traynor JP, Colhoun HM (January 2015). "Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010". JAMA. 313 (1): 37–44. doi:10.1001/jama.2014.16425. PMC 4426486. PMID 25562264.
- DiMeglio LA, Evans-Molina C, Oram RA (June 2018). "Type 1 diabetes". Lancet. 391 (10138): 2449–2462. doi:10.1016/S0140-6736(18)31320-5. PMC 6661119. PMID 29916386.
- Roy T, Lloyd CE (October 2012). "Epidemiology of depression and diabetes: a systematic review". Journal of Affective Disorders. 142 Suppl: S8–21. doi:10.1016/S0165-0327(12)70004-6. PMID 23062861.
- See JA, Kaukinen K, Makharia GK, Gibson PR, Murray JA (October 2015). "Practical insights into gluten-free diets". Nature Reviews. Gastroenterology & Hepatology (Review). 12 (10): 580–91. doi:10.1038/nrgastro.2015.156. PMID 26392070. S2CID 20270743.
Coeliac disease in T1DM is asymptomatic ...Clinical manifestations of coeliac disease, such as abdominal pain, gas, bloating, diarrhoea and weight loss can be present in patients with T1DM, but are often attributed to poor control of diabetes, gastroparesis or diabetic neuropathy
- Chen HS, Su LT, Lin SZ, Sung FC, Ko MC, Li CY (January 2012). "Increased risk of urinary tract calculi among patients with diabetes mellitus--a population-based cohort study". Urology. 79 (1): 86–92. doi:10.1016/j.urology.2011.07.1431. PMID 22119251.
- 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. S2CID 30653959.
- "Sexual Dysfunction in Women". Diabetes.co.uk. Diabetes Digital Media Ltd. Archived from the original on 9 November 2014. Retrieved 28 November 2014.
- Goswami SK, Vishwanath M, Gangadarappa SK, Razdan R, Inamdar MN (August 2014). "Efficacy of ellagic acid and sildenafil in diabetes-induced sexual dysfunction". Pharmacognosy Magazine. 10 (Suppl 3): S581–7. doi:10.4103/0973-1296.139790. PMC 4189276. PMID 25298678. ProQuest 1610759650.
- Escobar-Morreale HF, Roldán B, Barrio R, Alonso M, Sancho J, de la Calle H, García-Robles R (November 2000). "High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus". The Journal of Clinical Endocrinology and Metabolism. 85 (11): 4182–7. doi:10.1210/jcem.85.11.6931. PMID 11095451.
- Codner E, Escobar-Morreale HF (April 2007). "Clinical review: Hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus". The Journal of Clinical Endocrinology and Metabolism. 92 (4): 1209–16. doi:10.1210/jc.2006-2641. PMID 17284617.
- 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. 8 Suppl 8 (s8): 8–9. doi:10.1111/j.1399-5448.2007.00326.x. PMID 17767619.
- Kasper DL, Braunwald E, Fauci A, et al. (2005). Harrison's Principles of Internal Medicine (16th ed.). New York: McGraw-Hill. ISBN 978-0-07-139140-5.
- Soltesz G, Patterson CC, Dahlquist G (October 2007). "Worldwide childhood type 1 diabetes incidence--what can we learn from epidemiology?". Pediatric Diabetes. 8. 8 Suppl 6 (s6): 6–14. doi:10.1111/j.1399-5448.2007.00280.x. PMID 17727380. S2CID 28054025.
- "Fast Facts" (PDF). American Diabetes Association. Archived from the original (PDF) on 29 April 2015.
- Australian Institute of Health and Welfare (2015). "Incidence of type 1 diabetes in Australia 2000–2013". Archived from the original on 7 October 2016. Retrieved 19 October 2016.
- Shaw J (2012). "diabetes: the silent pandemic and its impact on Australia" (PDF). Archived (PDF) from the original on 7 October 2016. Retrieved 19 October 2016.
- Bottazzo GF, Florin-Christensen A, Doniach D (November 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 (April 2013). "Type 1 diabetes: translating mechanistic observations into effective clinical outcomes". Nature Reviews. Immunology. 13 (4): 243–56. doi:10.1038/nri3422. PMC 4172461. PMID 23524461.
- Johnson L (18 November 2008). "Study: Cost of diabetes $218B". USA Today. Associated Press. Archived from the original on 1 July 2012.
- Diabetes Research and Wellness Foundation Archived 11 May 2013 at the Wayback Machine
- Antvorskov JC, Josefsen K, Engkilde K, Funda DP, Buschard K (September 2014). "Dietary gluten and the development of type 1 diabetes". Diabetologia (Review). 57 (9): 1770–80. doi:10.1007/s00125-014-3265-1. PMC 4119241. PMID 24871322.
- Fairweather D, Rose NR (April 2002). "Type 1 diabetes: virus infection or autoimmune disease?". Nature Immunology. 3 (4): 338–40. doi:10.1038/ni0402-338. PMID 11919574. S2CID 12672403.
- Petzold A, Solimena M, Knoch KP (October 2015). "Mechanisms of Beta Cell Dysfunction Associated With Viral Infection". Current Diabetes Reports (Review). 15 (10): 73. doi:10.1007/s11892-015-0654-x. PMC 4539350. PMID 26280364.
So far, none of the hypotheses accounting for virus-induced beta cell autoimmunity has been supported by stringent evidence in humans, and the involvement of several mechanisms rather than just one is also plausible.
- Butalia S, Kaplan GG, Khokhar B, Rabi DM (December 2016). "Environmental Risk Factors and Type 1 Diabetes: Past, Present, and Future". Canadian Journal of Diabetes (Review). 40 (6): 586–593. doi:10.1016/j.jcjd.2016.05.002. PMID 27545597.
- Perrett KP, Jachno K, Nolan TM, Harrison LC (January 2019). "Association of Rotavirus Vaccination With the Incidence of Type 1 Diabetes in Children". JAMA Pediatrics. 173 (3): 280–282. doi:10.1001/jamapediatrics.2018.4578. PMC 6439878. PMID 30667473.
- Gómez-Rial J, Sánchez-Batán S, Rivero-Calle I, Pardo-Seco J, Martinón-Martínez JM, Salas A, Martinón-Torres F (2019). "Rotavirus infection beyond the gut". Infection and Drug Resistance. 12: 55–64. doi:10.2147/IDR.S186404. PMC 6307677. PMID 30636886.
- Bagley J, Paez-Cortez J, Tian C, Iacomini J (2008). "Gene therapy in type 1 diabetes". Critical Reviews in Immunology. 28 (4): 301–24. doi:10.1615/CritRevImmunol.v28.i4.30. PMID 19166382.
- Minami K, Seino S (March 2013). "Current status of regeneration of pancreatic β-cells". Journal of Diabetes Investigation. 4 (2): 131–41. doi:10.1111/jdi.12062. PMC 4019265. PMID 24843642.
- Pagliuca FW, Millman JR, Gürtler M, Segel M, Van Dervort A, Ryu JH, Peterson QP, Greiner D, Melton DA (October 2014). "Generation of functional human pancreatic β cells in vitro". Cell. 159 (2): 428–39. doi:10.1016/j.cell.2014.09.040. PMC 4617632. 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. S2CID 205280579.
- Lernmark A, Larsson HE (February 2013). "Immune therapy in type 1 diabetes mellitus". Nature Reviews. Endocrinology. 9 (2): 92–103. doi:10.1038/nrendo.2012.237. PMID 23296174. S2CID 10371556.
- "Rotavirus vaccination tied to lower rates of type 1 diabetes". Reuters. 22 January 2019. Retrieved 10 February 2019.
- Bakalar N (30 January 2019). "Rotavirus Vaccine May Protect Against Type 1 Diabetes". The New York Times. ISSN 0362-4331. Retrieved 10 February 2019.
- Ristori, G; Faustman, D; Matarese, G; Romano, S; Salvetti, M (December 2018). "Bridging the gap between vaccination with Bacille Calmette-Guérin (BCG) and immunological tolerance: the cases of type 1 diabetes and multiple sclerosis". Current Opinion in Immunology. 55: 89–96. doi:10.1016/j.coi.2018.09.016. PMID 30447407.
- Type 1 diabetes at Curlie
- Kids and Teens: Type 1 Diabetes at Curlie
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) – Diabetes in America Textbook (PDFs)
- IDF Diabetes Atlas
- Type 1 Diabetes at the American Diabetes Association
- ADA's Standards of Medical Care in Diabetes 2019