toxic ketones as a byproduct. ketoacidosis symptoms can develop rapidly, with frequent urination, excessive thirst, nausea, vomiting, and severe abdominal pain all common. more severe ketoacidosis can result in labored breathing, and loss of consciousness due to cerebral edema. people with type 1 diabetes experience diabetic ketoacidosis 1–5 times per 100 person-years, the majority of which result in hospitalization. 13–19% of type 1 diabetes-related deaths are caused by ketoacidosis, making ketoacidosis the leading cause of death in people with type 1 diabetes less than 58 years old. long-term complications in addition to the acute complications of diabetes, long-term hyperglycemia results in damage to the small blood vessels throughout the body. this damage tends to manifest particularly in the eyes, nerves, and kidneys causing diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy respectively. in the eyes, prolonged high blood sugar causes the blood vessels in the retina to become fragile. people with type 1 diabetes also have increased risk of cardiovascular disease, which is estimated to shorten the life of the average type 1 diabetic by 8–13 years. 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. 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 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. oral contraceptive pills can cause blood sugar imbalances in women who have diabetes. dosage changes can help address that, at the risk of side effects and complications. 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. autoimmune disorders people with type 1 diabetes are at an increased risk for developing several autoimmune disorders, particularly thyroid problems – around 20% of people with type 1 diabetes have hypothyroidism or hyperthyroidism, typically caused by hashimoto thyroiditis or graves' disease respectiveley. celiac disease affects 2–8% of people with type 1 diabetes, and is more common in those who were younger at diabetes diagnosis, and in white people. type 1 diabetics are also at increased risk of rheumatoid arthritis, lupus, autoimmune gastritis, pernicious anemia, vitiligo, and addison's disease. conversely, complex autoimmune syndromes caused by mutations in the immunity-related genes aire (causing autoimmune polyglandular syndrome), foxp3 (causing ipex syndrome), or stat3 include type 1 diabetes in their effects. prevention there is no way to prevent type 1 diabetes; however, the development of diabetes symptoms can be delayed in some people who are at high risk of developing the disease. in 2022 the fda approved an intravenous injection of teplizumab to delay the progression of type 1 diabetes in those older than eight who have already developed diabetes-related autoantibodies and problems with blood sugar control. in that population, the anti-cd3 monoclonal antibody teplizumab can delay the development of type 1 diabetes symptoms by around two years. in addition to anti-cd3 antibodies, several other immunosuppressive agents have been trialled with the aim of preventing beta cell destruction. large trials of cyclosporine treatment suggested that cyclosporine could improve insulin secretion in those recently diagnosed with type 1 diabetes; however, people who stopped taking cyclosporine rapidly stopped making insulin, and cyclosporine's kidney toxicity and increased risk of cancer prevented people from using it long-term. several other immunosuppressive agents – prednisone, azathioprine, anti-thymocyte globulin, mycophenolate, and antibodies against cd20 and il2 receptor α – have been the subject of research, but none have provided lasting protection from development of type 1 diabetes. there have also been clinical trials attempting to induce immune tolerance by vaccination with insulin, gad65, and various short peptides targeted by immune cells during type 1 diabetes; none have yet delayed or prevented development of disease. several trials have attempted dietary interventions with the hope of reducing the autoimmunity that leads to type 1 diabetes. trials that withheld cow's milk or gave infants formula free of bovine insulin decreased the development of β-cell-targeted antibodies, but did not prevent the development of type 1 diabetes. similarly, trials that gave high-risk individuals injected insulin, oral insulin, or nicotinamide did not prevent diabetes development. epidemiology type 1 diabetes makes up an estimated 10–15% of all diabetes cases or 11–22 million cases worldwide. symptoms can begin at any age, but onset is most common in children, with diagnoses slightly more common in 5 to 7 year olds, and much more common around the age of puberty. in contrast to most autoimmune diseases, type 1 diabetes is slightly more common in males than in females. in 2006, type 1 diabetes affected 440,000 children under 14 years of age and was the primary cause of diabetes in those less than 15 years of age. rates vary widely by country and region. incidence is highest in scandinavia, at 30–60 new cases per 100,000 children per year, intermediate in the u.s. and southern europe at 10–20 cases per 100,000 per year, and lowest in china, much of asia, and south america at 1–3 cases 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. since the 1950s, the incidence of type 1 diabetes has been gradually increasing across the world by an average 3–4% per year. the increase is more pronounced in countries that began with a lower incidence of type 1 diabetes. history the connection between diabetes and pancreatic damage was first described by the german pathologist martin schmidt, who in a 1902 paper noted inflammation around the pancreatic islet of a child who had died of diabetes. the connection between this inflammation and diabetes onset was further developed through the 1920s by shields warren, and the term "insulitis" was coined by hanns von meyenburg in 1940 to describe the phenomenon. 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. research 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 institutes of health, and in the uk via the national institute for health and care 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. organ replacement 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. there has also been substantial effort to develop a fully automated insulin delivery system or "artificial pancreas" that could sense glucose levels and inject appropriate insulin without conscious input from the user. current "hybrid closed-loop systems" use a continuous glucose monitor to sense blood sugar levels, and a subcutaneous insulin pump to deliver insulin; however, due to the delay between insulin injection and its action, current systems require the user to initiate insulin before taking meals. several improvements to these systems are currently undergoing clinical trials in humans, including a dual-hormone system that injects glucagon in addition to insulin, and an implantable device that injects insulin intraperitoneally where it can be absorbed more quickly. disease models various animal models of disease are used to understand the pathogenesis and etiology of type 1 diabetes. currently available models of t1d can be divided into spontaneously autoimmune, chemically induced, virus induced and genetically induced. the nonobese diabetic (nod) mouse is the most widely studied model of type 1 diabetes. it is an inbred strain that spontaneously develops type 1 diabetes in 30–100% of female mice depending on housing conditions. diabetes in nod mice is caused by several genes, primarily mhc genes involved in antigen presentation. like diabetic humans, nod mice develop islet autoantibodies and inflammation in the islet, followed by reduced insulin production and hyperglycemia. some features of human diabetes are exaggerated in nod mice, namely the mice have more severe islet inflammation than humans, and have a much more pronounced sex bias, with females developing diabetes far more frequently than males. in nod mice the onset of insulitis occurs at 3–4 weeks of age. the islets of langerhans are infiltrated by cd4+, cd8+ t lymphocytes, nk cells, b lymphocytes, dendritic cells, macrophages and neutrophils, similar to the disease process in humans. in addition to sex, breeding conditions, gut microbiome composition or diet also influence