Type 1 diabetes
[22][23][24][25][26] Children may also experience increased appetite, blurred vision, bedwetting, recurrent skin infections, candidiasis of the perineum, irritability, and reduced scholastic performance.[36] Conversely, some have postulated that reduced exposure to pathogens in the developed world increases the risk of autoimmune diseases, often called the hygiene hypothesis.Various studies of hygiene-related factors—including household crowding, daycare attendance, population density, childhood vaccinations, antihelminth medication, and antibiotic usage during early life or pregnancy—show no association with type 1 diabetes.This nomenclature informs medical professionals the patient has no insulin production and requires extensive monitoring to avoid severe hyperglycemia or hypoglycemia.[53] The National Institute for Health and Care Excellence now recommends closed-loop insulin systems as an option for all women with type 1 diabetes who are pregnant or planning pregnancy.[62] Similarly, the risk of exercise-induced hyperglycemia can be managed by avoiding exercise when insulin levels are very low, when blood sugar is extremely high (above 350 mg/dL or 19.4 mmol/L), or when one feels unwell.In T1DM, while exercise can improve lipid profiles and other aspects of health, it doesn't necessarily lead to better blood sugar control, and there are additional barriers such as fear of hypoglycemia.In some cases, people can receive transplants of the pancreas or isolated islet cells to restore insulin production and alleviate diabetic symptoms.The pancreases of people with type 1 diabetes tend to be smaller, lighter, and have abnormal blood vessels, nerve innervations, and extracellular matrix organization.[77] In addition, beta cells from people with type 1 diabetes sometimes overexpress HLA class I molecules (responsible for signaling to the immune system) and have increased endoplasmic reticulum stress and issues with synthesizing and folding new proteins, any of which could contribute to their demise.[78] Necroptosis can be triggered by activated T cells – which secrete toxic granzymes and perforin – or indirectly as a result of reduced blood flow or the generation of reactive oxygen species.[86][87] Beta cell glucose sensing and subsequent suppression of administered insulin secretion is absent, leading to islet hyperinsulinemia which inhibits glucagon release.[89] The major hypotheses are summarized in the following table:[90][88][89] In addition, autoimmune diabetes is characterized by a loss of islet specific sympathetic innervation.Increased BDNF and ROS that result from insulitis and beta cell death stimulate the p75 neurotrophin receptor (p75NTR), which acts to prune off axons.[93] Severe hypoglycemia that impairs someone's ability to eat is typically treated with injectable glucagon, which triggers glucose release from the liver into the bloodstream.[94] The other persistent risk is diabetic ketoacidosis – a state where lack of insulin results in cells burning fat rather than sugar, producing toxic ketones as a byproduct.[28] Ketoacidosis symptoms can develop rapidly, with frequent urination, excessive thirst, nausea, vomiting, and severe abdominal pain all common.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.[109] Sexual problems are common in women who have diabetes,[108] including reduced sensation in the genitals, dryness, difficulty/inability to orgasm, pain during sex, and decreased libido.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.[116] 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.Gene therapy approaches, while still in early stages, aim to alter genetic factors that contribute to beta-cell destruction by editing immune responses.[134] The Diabetes Research in Children Network Study Group observed blood sugar levels decrease rapidly in the first 15 minutes of exercise and continue to drop during the 75-minute session.[135] 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.[151][147] The advantage of the model is the progression of the prediabetic phase, which is very similar to human disease, with infiltration of islet by immune cells about a week before hyperglycemia is observed.The development of diabetes in AKITA mice is caused by a spontaneous point mutation in the Ins2 gene, which is responsible for the correct composition of insulin in the endoplasmic reticulum.Although environmental factors also play a significant role, the genetic susceptibility to T1D is well established, with several genes and loci implicated in disease development.These HLA variants are thought to influence the immune system’s ability to differentiate between self and non-self antigens, leading to the autoimmune destruction of pancreatic beta cells.While individual genes confer varying degrees of risk, it is the combination of several genetic factors, along with environmental triggers, that ultimately leads to disease onset.[167] Environmental factors such as viral infections, early childhood diet, and gut microbiome composition are thought to trigger the autoimmune process in genetically susceptible individuals.
SpecialtyEndocrinologySymptomsFrequent urinationincreased thirstweight lossComplicationsDiabetic ketoacidosishypoglycemiacardiovascular diseaseinsulinRisk factorsceliac diseaseDiagnostic methodautoantibodiesTeplizumabPrognosislife expectancyautoimmune diseaseimmune systemblood sugarhigh blood sugarincreased hungerblurry visiontirednessautoimmunebeta cellspancreasDiabetesglycated hemoglobintype 2C-peptideInsulin therapyinsulin pumpdiabetic dietnonketotic hyperosmolar comaheart diseasekidney failurefoot ulcersdamage to the eyeslow blood sugarScandinaviaKuwaitpolyuriapolydipsiaincreased appetitebedwettingcandidiasisperineumketonesβ-cellsIA-2βantigenβ-cellidiopathicenvironmental risksautoimmunitycaesarean sectionglutendietary fiberomega-3 fatty acidsenteroviruseshygiene hypothesisHLA class IIantigen presentationHLA-DRB1HLA-DQA1HLA-DQB1variation patternsHLA-DR3HLA-DR4HLA-DQ8HLA-DR15HLA-DQ6genome-wide association studiesantiviral drugdidanosineprotozoalpentamidinestatinsimmunosuppressantscyclosporin AtacrolimusleukemiaL-asparaginaseantibioticpancreatoduodenectomyWhipple ProcedurepancreatectomyWorld Health Organizationoral glucose tolerance testAmerican Diabetes Associationglutamic acid decarboxylaseDiabetes managementsubcutaneous injectionsyringecapillary blood testingglucose metercontinuous glucose monitorstandard of caremobile appNational Institute for Health and Care ExcellenceFood and Drug AdministrationamylinpramlintidemetforminGLP-1 receptor agonistsdipeptidyl peptidase-4 inhibitorsSGLT2 inhibitoroff-labelcarbohydratestransplantsTransplantation of the whole pancreasimmunosuppressive therapytransplant rejectionkidney transplantTransplantations of islets aloneportal veinDonislecelCD8+ T-cellsB-cellsadaptive immune systemregulatory T cellinsulitisCD4+ T cellsextracellular matrix