{{short description|Form of diabetes mellitus}} {{CS1 config|name-list-style=vanc|display-authors=6}} {{Use dmy dates|date=January 2023}} {{Infobox medical condition (new) | name = Type 1 diabetes | synonyms = Type 1 diabetes mellitus, insulin-dependent diabetes, insulin-dependent diabetes mellitus (IDDM), juvenile diabetes, childhood-onset diabetes | image = Blue circle for diabetes.svg | image_size = 200px | caption = A blue circle, the symbol for diabetes | field = Endocrinology | pronounce = {{IPAc-en|d|aɪ|ə|ˈ|b|iː|t|iː|z}} | symptoms = Frequent urination, increased thirst, weight loss | complications = Diabetic ketoacidosis, severe hypoglycemia, cardiovascular disease, and damage to the eyes, kidneys, and nerves | onset = At any age; over days to weeks | duration = Lifelong | causes = Body does not produce enough insulin | risks = Family history, celiac disease, autoimmune diseases | diagnosis = High blood sugar levels, autoantibodies targeting insulin-producing cells | differential = | prevention = Teplizumab (Delays onset but does not permanently prevent onset of disease) | treatment = Monitoring blood sugar, injected insulin, managing diet | prognosis = 10-12 years shorter life expectancy<ref>{{cite journal |last1=Zheng |first1=Yan |last2=Permanyer |first2=Iñaki |last3=Canudas-Romo |first3=Vladimir |last4=Aburto |first4=José Manuel |last5=Nigri |first5=Andrea |last6=Plana-Ripoll |first6=Oleguer |date=2023 |title=Lifespan variation among people with a given disease or condition |journal=PLOS ONE |volume=18 |issue=9 |article-number=e0290962 |doi=10.1371/journal.pone.0290962 |doi-access=free |issn=1932-6203 |pmid=37656703 |pmc=10473533 |bibcode=2023PLoSO..1890962Z}}</ref><ref>{{cite journal |last1=Livingstone |first1=Shona J. |last2=Levin |first2=Daniel |last3=Looker |first3=Helen C. |last4=Lindsay |first4=Robert S. |last5=Wild |first5=Sarah H. |last6=Joss |first6=Nicola |last7=Leese |first7=Graham |last8=Leslie |first8=Peter |last9=McCrimmon |first9=Rory J. |last10=Metcalfe |first10=Wendy |last11=McKnight |first11=John A. |last12=Morris |first12=Andrew D. |last13=Pearson |first13=Donald W. M. |last14=Petrie |first14=John R. |last15=Philip |first15=Sam |date=2015-01-06 |title=Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010 |journal=JAMA |volume=313 |issue=1 |pages=37–44 |doi=10.1001/jama.2014.16425 |issn=1538-3598 |pmc=4426486 |pmid=25562264}}</ref><ref>{{cite journal |last1=Arffman |first1=Martti |last2=Hakkarainen |first2=Pirjo |last3=Keskimäki |first3=Ilmo |last4=Oksanen |first4=Tuula |last5=Sund |first5=Reijo |date=April 2023 |title=Long-term and recent trends in survival and life expectancy for people with type 1 diabetes in Finland |journal=Diabetes Research and Clinical Practice |volume=198 |article-number=110580 |doi=10.1016/j.diabres.2023.110580 |issn=1872-8227 |pmid=36804193|doi-access=free}}</ref> | frequency = 9 million cases globally<ref name=WHO11/> }}
'''Type 1 diabetes''' ('''T1D'''), or '''type 1 diabetes mellitus''', is an autoimmune disease that occurs when the body's immune system destroys beta cells in the pancreas that produce the hormone insulin.<ref name=WHO2016/> Insulin is required by the body to store and convert blood sugar into energy.<ref name=NIH2014Type/> T1D results in high blood sugar levels in the body prior to treatment.<ref name=NIH2014Cau/> Common symptoms include frequent urination, increased thirst, increased hunger, weight loss, and other complications.<ref name=WHO2016/><ref>{{cite journal |vauthors=Torpy JM, Lynm C, Glass RM |title=JAMA patient page. Type 1 diabetes |journal=JAMA |volume=298 |issue=12 |page=1472 |date=September 2007 |pmid=17895465 |doi=10.1001/jama.298.12.1472}}</ref> Additional symptoms may include blurry vision, tiredness, and slow wound healing (owing to impaired blood flow).<ref name=NIH2014Type>{{cite web |title=Types of Diabetes |date=February 2014 |website=NIDDK |url=https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes?dkrd=hiscr0001 |access-date=31 July 2016 |url-status=live |archive-url=https://web.archive.org/web/20160816162556/https://www.niddk.nih.gov/health-information/diabetes/types |archive-date=16 August 2016}}</ref> While some cases take longer, symptoms usually appear within weeks or a few months.<ref>{{cite web |title=NIDDK Central Repository - Diabetes Prevention Trial of Type 1 Diabetes (DPT-1) |url=https://repository.niddk.nih.gov/studies/dpt-1/#:~:text=The%20Diabetes%20Prevention%20Trial%E2%80%94Type,relatives%20of%20patients%20with%20diabetes|archive-url=https://web.archive.org/web/20190604213427/https://repository.niddk.nih.gov/studies/dpt-1/#:~:text=The%20Diabetes%20Prevention%20Trial%E2%80%94Type,relatives%20of%20patients%20with%20diabetes|archive-date=4 June 2019}}</ref><ref name=NIH2014Cau/>
The cause of type 1 diabetes is not completely understood,<ref name=WHO2016>{{cite web |title=Diabetes Fact sheet N°312 |work=WHO |date=November 2016 |url=https://www.who.int/mediacentre/factsheets/fs312/en/ |access-date=29 May 2017 |url-status=live |archive-url=https://web.archive.org/web/20130826174444/http://www.who.int/mediacentre/factsheets/fs312/en/ |archive-date=26 August 2013}}</ref> but it is believed to involve a combination of genetic and environmental factors.<ref>{{cite journal |date=2008 |author14=Type 1 Diabetes Genetics Consortium |title=HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: Analysis of the type 1 diabetes genetics consortium families |journal=Diabetes |volume=57 |issue=4 |pages=1084–1092 |vauthors=Erlich H, Valdes AM, Noble J, Carlson JA, Varney M, Concannon P, Mychaleckyj JC, Todd JA, Bonella P, Fear AL, Lavant E, Louey A, Moonsamy P |pmid=18252895 |doi=10.2337/db07-1331 |pmc=4103420}}</ref><ref name="NIH2014Cau"/> The underlying mechanism involves an autoimmune destruction of the insulin-producing beta cells in the pancreas.<ref name=NIH2014Type/> Diabetes is diagnosed by testing the level of sugar or glycated hemoglobin (HbA1C) in the blood.<ref name=Change2014/><ref name=NIH2015Diag>{{cite web |title=Diagnosis of Diabetes and Prediabetes |date=May 2015 |website=NIDDK |url=https://www.niddk.nih.gov/health-information/diabetes/diagnosis-diabetes-prediabetes |access-date=31 July 2016 |archive-url=https://web.archive.org/web/20160816185123/https://www.niddk.nih.gov/health-information/diabetes/diagnosis-diabetes-prediabetes |archive-date=16 August 2016}}</ref>
Type 1 diabetes can be distinguished from type 2 by testing for the presence of autoantibodies<ref name="Change2014"/> and/or declining levels/absence of C-peptide.
There is no known way to prevent type 1 diabetes.<ref name=WHO2016/> Treatment with insulin is required for survival.<ref name=NIH2014Cau>{{cite web |title=Causes of Diabetes |date=August 2014 |website=NIDDK |url=https://www.niddk.nih.gov/health-information/diabetes/overview/symptoms-causes?dkrd=hiscr0005 |access-date=31 July 2016 |url-status=live |archive-url=https://web.archive.org/web/20160810063435/https://www.niddk.nih.gov/health-information/diabetes/causes |archive-date=10 August 2016}}</ref> Insulin therapy is usually given by injection just under the skin but can also be delivered by an insulin pump.<ref>{{cite web |title=Alternative Devices for Taking Insulin |date=July 2016 |website=NIDDK |url=https://www.niddk.nih.gov/health-information/diabetes/manage-monitoring-diabetes/alternative-devices-taking-insulin |access-date=31 July 2016 |archive-url=https://web.archive.org/web/20160816170132/https://www.niddk.nih.gov/health-information/diabetes/manage-monitoring-diabetes/alternative-devices-taking-insulin |archive-date=16 August 2016}}</ref> A diabetic diet, exercise, and lifestyle modifications are considered cornerstones of management.<ref name=NIH2014Type/> If left untreated, diabetes can cause many complications.<ref name=WHO2016/> Complications of relatively rapid onset include diabetic ketoacidosis and nonketotic hyperosmolar coma.<ref name=Change2014/> Long-term complications include heart disease, stroke, kidney failure, foot ulcers, and damage to the eyes.<ref name=WHO2016/> Furthermore, since insulin lowers blood sugar levels, complications may arise from low blood sugar if more insulin is taken than necessary.<ref name=Change2014/>
Type 1 diabetes makes up an estimated 5–10% of all diabetes cases.<ref name=Lancet06>{{cite journal |vauthors=Daneman D |title=Type 1 diabetes |journal=Lancet |volume=367 |issue=9513 |pages=847–858 |date=March 2006 |pmid=16530579 |doi=10.1016/S0140-6736(06)68341-4 |s2cid=21485081}}</ref> The number of people affected globally is unknown, although it is estimated that about 80,000 children develop the disease each year.<ref name=Change2014>{{cite journal |vauthors=Chiang JL, Kirkman MS, Laffel LM, Peters AL |title=Type 1 diabetes through the life span: a position statement of the American Diabetes Association |journal=Diabetes Care |volume=37 |issue=7 |pages=2034–2054 |date=July 2014 |pmid=24935775 |doi=10.2337/dc14-1140 |pmc=5865481}}</ref> Within the United States the number of people affected is estimated to be one to three million.<ref name=Change2014/><ref>{{cite web |title=Fast Facts Data and Statistics about Diabetes |publisher=American Diabetes Association |url=http://professional.diabetes.org/ResourcesForProfessionals.aspx?cid=91777 |access-date=25 July 2014 |url-status=live |archive-url=https://web.archive.org/web/20151216001425/http://professional.diabetes.org/ResourcesForProfessionals.aspx?cid=91777 |archive-date=16 December 2015}}</ref> Rates of disease vary widely, with approximately one 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.<ref>{{cite book |title=Global report on diabetes |date=2016 |publisher=World Health Organization |isbn=978-92-4-156525-7 |pages=26–27 |url=http://apps.who.int/iris/bitstream/10665/204871/1/9789241565257_eng.pdf?ua=1 |access-date=31 July 2016 |url-status=live |archive-url=https://web.archive.org/web/20161007002653/http://apps.who.int/iris/bitstream/10665/204871/1/9789241565257_eng.pdf?ua=1 |archive-date=7 October 2016}}</ref><ref>{{cite book |vauthors=Skyler J |title=Atlas of diabetes |date=2012 |publisher=Springer |location=New York |isbn=978-1-4614-1028-7 |pages=67–68 |edition=4th |url=https://books.google.com/books?id=5n-RhyGrrpcC&pg=PA68 |url-status=live |archive-url=https://web.archive.org/web/20170908155611/https://books.google.com/books?id=5n-RhyGrrpcC&pg=PA68 |archive-date=8 September 2017}}</ref> It typically begins in children and young adults but can begin at any age.<ref name=NIH2014Cau/><ref name=":5"/>
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==Signs and symptoms== thumb|upright=1.4|Overview of the most significant symptoms of untreated type one diabetes
Type 1 diabetes can develop at any age, with a peak in onsets during childhood and adolescence. Adult onsets on the other hand are often initially misdiagnosed as type 2.<ref name=":5">{{cite journal |last1=Fang |first1=Michael |last2=Wang |first2=Dan |last3=Echouffo-Tcheugui |first3=Justin B |last4=Selvin |first4=Elizabeth |title=Age at Diagnosis in U.S. Adults With Type 1 Diabetes |journal=Ann Intern Med |date=2023 |volume=176 |issue=11 |pages=1567–1568 |pmid=37748184 |doi=10.7326/M23-1707 |pmc=10841362}}</ref><ref>{{cite web |last1=McNulty |first1=Rose |title=Many Cases of Adult-Onset T1D Are Diagnosed After Age 30, Study Finds |date=7 October 2023 |website=ajmc |url=https://www.ajmc.com/view/many-cases-of-adult-onset-t1d-are-diagnosed-after-age-30-study-finds |access-date=29 April 2024}}</ref>{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc=Table 36.1}}<ref name=":4">{{cite journal |title=WHAT IS TYPE 1 DIABETES? |date=April 18, 2016 |journal=Diabetes Daily |url=https://www.diabetesdaily.com/learn-about-diabetes/basics/what-is-type-1-diabetes/}}</ref> The major sign of type 1 diabetes is very high blood sugar, which typically manifests in children as a few days to weeks of polyuria (increased urination), polydipsia (increased thirst), and weight loss after being exposed to a triggering factor including infections, strenuous exercise, dehydration.<ref>{{cite journal |date=2003 |author10=Finnish TRIGR Study Group |title=Enterovirus infections as a risk factor for type I diabetes: Virus analyses in a dietary intervention trial |journal=Clinical and Experimental Immunology |volume=132 |issue=2 |pages=271–277 |vauthors=Sadeharju K, Hämäläinen AM, Knip M, Lönnrot M, Koskela P, Virtanen SM, Ilonen J, Akerblom HK, Hyöty H |pmid=12699416 |doi=10.1046/j.1365-2249.2003.02147.x |pmc=1808709}}</ref><ref>{{cite journal |title=Ketoacidosis in Children and Adolescents with Newly Diagnosed Type 1 Diabetes During the COVID-19 Pandemic in Germany |date=2020 |journal=JAMA |volume=324 |issue=8 |pages=801–804 |vauthors=Kamrath C, Mönkemöller K, Biester T, Rohrer TR, Warncke K, Hammersen J, Holl RW |pmid=32702751 |doi=10.1001/jama.2020.13445 |pmc=7372511}}</ref><ref>{{cite journal |title=Diabetic Ketoacidosis in Children and Adolescents; Diagnostic and Therapeutic Pitfalls |date=2023 |journal=Diagnostics |volume=13 |issue=15 |page=2602 |vauthors=Kostopoulou E, Sinopidis X, Fouzas S, Gkentzi D, Dassios T, Roupakias S, Dimitriou G |pmid=37568965 |doi=10.3390/diagnostics13152602 |doi-access=free |pmc=10416834}}</ref>{{sfn|Wolsdorf|Garvey|2016|loc="Type 1 Diabetes"}}{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Clinical presentation"}} Children may also experience increased appetite, blurred vision, bedwetting, recurrent skin infections, candidiasis of the perineum, irritability, and reduced mental acumen.{{sfn|Wolsdorf|Garvey|2016|loc="Type 1 Diabetes"}}{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Clinical presentation"}} Adults with type 1 diabetes tend to have more varied symptoms, which come on over months, rather than days or weeks.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2449}}{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Clinical presentation"}}
Prolonged lack of insulin can cause diabetic ketoacidosis, characterized by fruity breath odor, mental confusion, persistent fatigue, dry or flushed skin, abdominal pain, nausea or vomiting, and labored breathing.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2449}}<ref name=ADA-Keto>{{cite web |title=DKA (Ketoacidosis) & Ketones |publisher=American Diabetes Association |url=https://www.diabetes.org/diabetes/complications/dka-ketoacidosis-ketones |access-date=28 July 2021}}</ref> Blood and urine tests reveal unusually high glucose and ketones in the blood and urine.{{sfn|Delli|Lernmark|2016|loc="Signs and symptoms"}} Untreated ketoacidosis can rapidly progress to loss of consciousness, coma, and death.{{sfn|Delli|Lernmark|2016|loc="Signs and symptoms"}} The percentage of children whose type 1 diabetes begins with an episode of diabetic ketoacidosis varies widely by geography, as low as 15% in parts of Europe and North America, and as high as 80% in the developing world.{{sfn|Delli|Lernmark|2016|loc="Signs and symptoms"}}
==Causes== Type 1 diabetes is caused by the destruction of β-cells—the only cells in the body that produce insulin—and the consequent progressive insulin deficiency. Without insulin, the body cannot respond effectively to increases in blood sugar. Due to this, people with diabetes have persistent hyperglycemia.{{sfn|Katsarou|Gudbjörnsdottir|Rawshani|Dabelea|2017|p=1}} In 70–90% of cases, β-cells are destroyed by one's own immune system, for reasons that are not entirely clear.{{sfn|Katsarou|Gudbjörnsdottir|Rawshani|Dabelea|2017|p=1}} The best-studied components of this autoimmune response are β-cell-targeted antibodies that begin to develop in the months or years before symptoms arise.{{sfn|Katsarou|Gudbjörnsdottir|Rawshani|Dabelea|2017|p=1}} Typically, someone will first develop antibodies against insulin or the protein GAD65, followed eventually by antibodies against the proteins IA-2, IA-2β, and/or ZNT8. People with a higher level of these antibodies, especially those who develop them earlier in life, are at higher risk for developing symptomatic type 1 diabetes.{{sfn|Katsarou|Gudbjörnsdottir|Rawshani|Dabelea|2017|loc="Epidemiology"}} The trigger for the development of these antibodies remains unclear.{{sfn|Katsarou|Gudbjörnsdottir|Rawshani|Dabelea|2017|loc="Introduction"}} Several explanatory theories have been put forward, and the cause may involve genetic susceptibility, a diabetogenic trigger, and/or exposure to an antigen.<ref name=knip2005>{{cite journal |vauthors=Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Akerblom HK |title=Environmental triggers and determinants of type 1 diabetes |journal=Diabetes |volume=54 |issue=Suppl 2 |pages=S125–S136 |date=December 2005 |pmid=16306330 |doi=10.2337/diabetes.54.suppl_2.S125 |doi-access=free}}</ref> The remaining 10–30% of type 1 diabetics have β-cell destruction but no sign of autoimmunity; this is called idiopathic type 1 diabetes (its cause is unknown).{{sfn|Katsarou|Gudbjörnsdottir|Rawshani|Dabelea|2017|p=1}}
===Environmental=== Various environmental risks have been studied in an attempt to understand what triggers β-cell destroying autoimmunity. Many aspects of environment and life history are associated with slight increases in type 1 diabetes risk; however, the connection between each risk and diabetes often remains unclear. Type 1 diabetes risk is slightly higher for children whose mothers are obese or older than 35, or for children born by caesarean section.{{sfn|Norris|Johnson|Stene|2020|loc="Environmental factors"}} Similarly, a child's weight gain in the first year of life, total weight, and BMI are associated with slightly increased type 1 diabetes risk.{{sfn|Norris|Johnson|Stene|2020|loc="Environmental factors"}} Some dietary habits have also been associated with type 1 diabetes risk, namely consumption of cow's milk and dietary sugar intake.{{sfn|Norris|Johnson|Stene|2020|loc="Environmental factors"}} Animal studies and some large human studies have found small associations between type 1 diabetes risk and intake of gluten or dietary fiber; however, other large human studies have found no such association.{{sfn|Norris|Johnson|Stene|2020|loc="Environmental factors"}} Many potential environmental triggers have been investigated in large human studies and found to be unassociated with type 1 diabetes risk including duration of breastfeeding, time of introduction of cow milk into the diet, vitamin D consumption, blood levels of active vitamin D, and maternal intake of omega-3 fatty acids.{{sfn|Norris|Johnson|Stene|2020|loc="Environmental factors"}}{{sfn|Norris|Johnson|Stene|2020|loc="Trends in epidemiology"}}
A longstanding hypothesis for an environmental trigger is that some viral infection early in life contributes to type 1 diabetes development. Much of this work has focused on enteroviruses, with some studies finding slight associations with type 1 diabetes, and others finding none.{{sfn|Norris|Johnson|Stene|2020|loc="Infections"}} Large human studies have searched for, but not yet found an association between type 1 diabetes and various other viral infections, including infections of the mother during pregnancy.{{sfn|Norris|Johnson|Stene|2020|loc="Infections"}} 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, antihelminthic medication, and antibiotic use during early life or pregnancy—show no association with type 1 diabetes.{{sfn|Norris|Johnson|Stene|2020|loc="The hygiene hypothesis and proxies of microbial exposures"}}
===Genetics=== Type 1 diabetes is partially caused by genetics, and family members of type 1 diabetics have a higher risk of developing the disease themselves. In the general population, the risk of developing type 1 diabetes is around 1 in 250. For someone whose parent has type 1 diabetes, the risk rises to 1–9%. If a sibling has type 1 diabetes, the risk is 6–7%. If someone's identical twin has type 1 diabetes, they have a 30–70% risk of developing it themselves.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2450}}
About half of the disease's heritability is due to variations in three HLA class II genes involved in antigen presentation: ''HLA-DRB1'', ''HLA-DQA1'', and ''HLA-DQB1''.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2450}} The variation patterns associated with increased risk of type 1 diabetes are called HLA-DR3 and HLA-DR4-HLA-DQ8, and are common in people of European descent. A pattern associated with reduced risk of type 1 diabetes is called HLA-DR15-HLA-DQ6.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2450}} Large genome-wide association studies have identified dozens of other genes associated with type 1 diabetes risk, mostly genes involved in the immune system.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2450}}
===Chemicals and drugs=== Some medicines can reduce insulin production or damage β cells, resulting in a disease that resembles type 1 diabetes. The antiviral drug didanosine triggers pancreas inflammation in 5 to 10% of those who take it, sometimes causing lasting β-cell damage.{{sfn|Repaske|2016|loc="Additional medications that decrease insulin release"}} Similarly, up to 5% of those who take the anti-protozoal drug pentamidine experience β-cell destruction and diabetes.{{sfn|Repaske|2016|loc="Additional medications that decrease insulin release"}} Several other drugs cause diabetes by reversibly reducing insulin secretion, namely statins (which may also damage β cells), the post-transplant immunosuppressants cyclosporin A and tacrolimus, the leukemia drug L-asparaginase, and the antibiotic gatifloxicin.{{sfn|Repaske|2016|loc="Additional medications that decrease insulin release"}}{{sfn|Repaske|2016|loc="A common medication that decreases insulin release"}}
===Post-operative changes=== One cause of Type 1 diabetes is through surgery. This is due to the destruction or intentional removal of a portion of or the entire pancreas. This decreases the number of beta-islet cells capable of producing insulin greatly, resulting in an acquired form of Type 1 diabetes known as pancreatogenic diabetes mellitus.<ref>{{citation |last1=Fuks |first1=David |title=Enhanced recovery after hepatopancreatobiliary surgery |date=2016 |work=Laparoscopic Liver, Pancreas, and Biliary Surgery |pages=141–147 |publisher=John Wiley & Sons, Ltd |language=en |isbn=978-1-118-78116-6 |last2=Aloia |first2=Thomas A. |last3=Gayet |first3=Brice |doi=10.1002/9781118781166.ch9 |url=https://onlinelibrary.wiley.com/doi/10.1002/9781118781166.ch9 |access-date=2025-01-15|url-access=subscription }}</ref> This type of diabetes is most often seen in patients that undergo a pancreatoduodenectomy (a.k.a. Whipple procedure) or a total pancreatectomy.<ref>{{cite journal |last1=Lee |first1=Cynthia Ying Chian |last2=Depczynski |first2=Barbara |last3=Poynten |first3=Ann |last4=Haghighi |first4=Koroush S. |title=Diabetes-related outcomes after pancreatic surgery |date=2020 |journal=ANZ Journal of Surgery |language=en |volume=90 |issue=10 |pages=2004–2010 |issn=1445-2197 |doi=10.1111/ans.16129 |pmid=32691521 |url=https://onlinelibrary.wiley.com/doi/10.1111/ans.16129|url-access=subscription }}</ref>
Patients who undergo a total pancreatectomy are medically recognized as a "brittle diabetic". This nomenclature informs medical professionals that the patient has no insulin production and requires extensive monitoring to avoid severe hyperglycemia or hypoglycemia.<ref>{{citation |last1=Nevler |first1=Avinoam |title=Survival and Late Morbidity after Resection of Pancreatic Cancer |date=2023 |work=The Pancreas |pages=1218–1231 |publisher=John Wiley & Sons, Ltd |language=en |isbn=978-1-119-87600-7 |last2=Yeo |first2=Charles J. |doi=10.1002/9781119876007.ch156 |url=https://onlinelibrary.wiley.com/doi/10.1002/9781119876007.ch156 |access-date=2025-01-15|url-access=subscription }}</ref> Hypoglycemia is significantly more worrying in these patients due to the potential for coma and even death, as hyperglycemia causes more subtle damage over a longer period of time and only affects consciousness at severe levels. Many of these patients require an insulin pump that constantly injects insulin to reduce their sugar levels .<ref>{{citation |last1=Helmberger |first1=Thomas K. |title=Diseases of the Pancreas |date=2023 |work=Diseases of the Abdomen and Pelvis 2023-2026: Diagnostic Imaging |pages=131–143 |editor-last=Hodler |editor-first=Juerg |place=Cham |publisher=Springer International Publishing |language=en |isbn=978-3-031-27355-1 |last2=Manfredi |first2=Riccardo |editor2-last=Kubik-Huch |editor2-first=Rahel A. |editor3-last=Roos |editor3-first=Justus E. |editor4-last=von Schulthess |editor4-first=Gustav K. |doi=10.1007/978-3-031-27355-1_9 |doi-access=free }}</ref>
==Diagnosis== Diabetes is typically diagnosed by a blood test showing unusually high blood sugar. The World Health Organization defines diabetes as blood sugar levels at or above 7.0 mmol/L (126 mg/dL) after fasting for at least eight hours, or a glucose level at or above 11.1 mmol/L (200 mg/dL) two hours after an oral glucose tolerance test.<ref name=WHO2006>{{cite book |title=Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycemia |publisher=World Health Organization |location=Geneva |page=1 |year=2006 |isbn=978-92-4-159493-6 |url=https://www.who.int/diabetes/publications/Definition%20and%20diagnosis%20of%20diabetes_new.pdf |access-date=28 July 2021}}</ref> The American Diabetes Association additionally recommends a diagnosis of diabetes for anyone with symptoms of hyperglycemia and blood sugar at any time at or above 11.1 mmol/L, or glycated hemoglobin (hemoglobin A1C) levels at or above 48 mmol/mol (6.5%).<ref name=ADA2021>{{cite journal |author=American Diabetes Association |title=2. Classification and Diagnosis of Diabetes: ''Standards of Medical Care in Diabetes-2021'' |journal=Diabetes Care |volume=44 |issue=Suppl 1 |pages=S15–S33 |date=January 2021 |publisher=American Diabetes Association |pmid=33298413 |doi=10.2337/dc21-S002 |doi-access=free}}</ref>
Once a diagnosis of diabetes is established, type 1 diabetes is distinguished from other types by a blood test for the presence of autoantibodies that target various components of the beta cell.{{sfn|Butler|Misselbrook|2020|loc="What is the next investigation?"}} The most commonly available tests detect antibodies against glutamic acid decarboxylase, the beta cell cytoplasm, or insulin, each of which is targeted by antibodies in around 80% of type 1 diabetics.{{sfn|Butler|Misselbrook|2020|loc="What is the next investigation?"}} Some healthcare providers also have access to tests for antibodies targeting the beta cell proteins IA-2 and ZnT8; these antibodies are present in around 58% and 80% of people with type 1 diabetes, respectively.{{sfn|Butler|Misselbrook|2020|loc="What is the next investigation?"}} Some also test for C-peptide, a byproduct of insulin synthesis. Very low C-peptide levels are suggestive of type 1 diabetes.{{sfn|Butler|Misselbrook|2020|loc="What is the next investigation?"}}
The median age of type 1 diabetes diagnosis in the United States is 24 years of age.<ref>{{cite web |url=https://www.usnews.com/news/health-news/articles/2023-09-28/over-a-third-of-adults-with-type-1-diabetes-werent-diagnosed-until-after-30 |title=Over a Third of Adults With Type 1 Diabetes Weren't Diagnosed Until After 30 |work=U.S. News & World Report |date=28 September 2023 |access-date=23 May 2025}}</ref>
==Management== {{Further|Diabetes management}}
The mainstay of type 1 diabetes treatment is the regular injection of insulin to manage hyperglycemia.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2453}} Injections of insulin via subcutaneous injection using either a syringe or an insulin pump are necessary multiple times per day, adjusting dosages to account for food intake, blood glucose levels, and physical activity.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2453}} The goal of treatment is to maintain blood sugar in a normal range—80–130 mg/dL (4.4–7.2 mmol/L) before a meal; <180 mg/dL (10.0 mmol/L) after—as often as possible.{{sfn|Katsarou|Gudbjörnsdottir|Rawshani|Dabelea|2017|p=11}} To achieve this, people with diabetes often monitor their blood glucose levels at home. Around 83% of type 1 diabetics monitor their blood glucose by capillary blood testing: pricking the finger to draw a drop of blood, and determining blood glucose with a glucose meter.{{sfn|Smith|Harris|2018|loc="Self monitoring"}} The American Diabetes Association recommends testing blood glucose around 6–10 times per day: before each meal, before exercise, at bedtime, occasionally after a meal, and any time someone feels the symptoms of hypoglycemia.{{sfn|Smith|Harris|2018|loc="Self monitoring"}} Around 17% of people with type 1 diabetes use a continuous glucose monitor, a device with a sensor under the skin that constantly measures glucose levels and communicates those levels to an external device.{{sfn|Smith|Harris|2018|loc="Self monitoring"}} Continuous glucose monitoring is associated with better blood sugar control than capillary blood testing alone; however, continuous glucose monitoring tends to be substantially more expensive.{{sfn|Smith|Harris|2018|loc="Self monitoring"}}<!--Anything else to add on this?--> Healthcare providers can also monitor someone's hemoglobin A1C levels, which reflect the average blood sugar over the last three months.{{sfn|American Diabetes Association (6)|2021|loc="Glycemic assessment"}} The American Diabetes Association recommends a goal of keeping hemoglobin A1C levels under 7% for most adults and 7.5% for children.{{sfn|American Diabetes Association (6)|2021|loc="Glycemic assessment"}}{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="Management of clinical disease"}}
The goal of insulin therapy is to mimic normal pancreatic insulin secretion: low levels of insulin are constantly present to support basic metabolism, plus the two-phase secretion of additional insulin in response to high blood sugar, then an extended phase of continued insulin secretion.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Insulin Therapy"}} This is accomplished by combining different insulin preparations that act with differing speeds and durations. The standard of care for type 1 diabetes is a bolus of rapid-acting insulin 10–15 minutes before each meal or snack, and as-needed to correct hyperglycemia.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Insulin Therapy"}} In addition, constant low levels of insulin are achieved with one or two daily doses of long-acting insulin, or by steady infusion by an insulin pump.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Insulin Therapy"}} The exact dose of insulin appropriate for each injection depends on the content of the meal/snack, and the person's sensitivity to insulin, and is therefore typically calculated by the individual with diabetes or a family member by hand or assistive device (calculator, chart, mobile app, etc.).{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Insulin Therapy"}} People who cannot manage these intensive insulin regimens are sometimes prescribed alternate plans relying on mixtures of rapid- or short-acting and intermediate-acting insulin, which are administered at fixed times along with meals of pre-planned times and carbohydrate composition.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Insulin Therapy"}} 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.<ref>{{cite web |title=Overview {{!}} Diabetes in pregnancy: management from preconception to the postnatal period {{!}} Guidance {{!}} NICE |date=2015-02-25 |website=nice.org.uk |url=https://www.nice.org.uk/guidance/ng3 |access-date=2024-01-31}}</ref><ref>{{cite journal |title=Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes |last1=Lee |first1=Tara T.M. |last2=Collett |first2=Corinne |last3=Bergford |first3=Simon |last4=Hartnell |first4=Sara |last5=Scott |first5=Eleanor M. |last6=Lindsay |first6=Robert S. |last7=Hunt |first7=Katharine F. |last8=McCance |first8=David R. |last9=Barnard-Kelly |first9=Katharine |last10=Rankin |first10=David |last11=Lawton |first11=Julia |last12=Reynolds |first12=Rebecca M. |last13=Flanagan |first13=Emma |last14=Hammond |first14=Matthew |last15=Shepstone |first15=Lee |date=2023-10-26 |journal=New England Journal of Medicine |language=en |volume=389 |issue=17 |pages=1566–1578 |issn=0028-4793 |pmid=37796241 |doi=10.1056/NEJMoa2303911 |url=https://www.nejm.org/doi/10.1056/NEJMoa2303911 |access-date=31 January 2024 |url-status=live |archive-url=https://web.archive.org/web/20231105204533/https://www.nejm.org/doi/10.1056/NEJMoa2303911 |archive-date=5 November 2023|url-access=subscription }}</ref><ref>{{cite journal |title=Closed-loop insulin systems are effective for pregnant women with type 1 diabetes |date=16 January 2024 |journal=NIHR Evidence |doi=10.3310/nihrevidence_61786 |url=https://evidence.nihr.ac.uk/alert/closed-loop-insulin-systems-are-effective-for-pregnant-women-with-type-1-diabetes/|url-access=subscription |doi-access=free }}</ref>
A non-insulin medication approved by the U.S. Food and Drug Administration for treating type 1 diabetes is the amylin analog pramlintide, which replaces the beta-cell hormone amylin. The addition of pramlintide to mealtime insulin injections reduces the boost in blood sugar after a meal, improving blood sugar control.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Use of Adjunctive Drugs in T1DM"}} Occasionally, metformin, GLP-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, or SGLT2 inhibitor are prescribed off-label to people with type 1 diabetes. Fewer than 5% of people with type 1 diabetes use these drugs.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2453}}
===Lifestyle=== Besides insulin, the major way type 1 diabetics control their blood sugar is by learning how various foods impact their blood sugar levels.<!--Cite--> This is primarily done by tracking their intake of carbohydrates, the type of food with the greatest impact on blood sugar.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Nutrition Therapy"}} In general, people with type 1 diabetes are advised to follow an individualized eating plan rather than a pre-decided one.<ref name=ups>{{cite journal |vauthors=Seckold R, Fisher E, de Bock M, King BR, Smart CE |title=The ups and downs of low-carbohydrate diets in the management of Type 1 diabetes: a review of clinical outcomes |journal=Diabetic Medicine |volume=36 |issue=3 |pages=326–334 |date=March 2019 |type=Review |pmid=30362180 |doi=10.1111/dme.13845 |s2cid=53102654 |quote=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.}}</ref> There are camps for children to teach them how and when to use or monitor their insulin without parental help.<ref>{{cite journal |vauthors=Ly TT |title=Technology and type 1 diabetes: Closed-loop therapies |date=2015 |journal=Current Pediatrics Reports |volume=3 |issue=2 |pages=170–176 |doi=10.1007/s40124-015-0083-y |s2cid=68302123}}</ref> 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.<ref>{{cite web |title=Stress |publisher=American Diabetes Association |website=diabetes.org |url=http://www.diabetes.org/living-with-diabetes/complications/mental-health/stress.html |access-date=11 November 2014 |archive-url=https://web.archive.org/web/20141112012601/http://www.diabetes.org/living-with-diabetes/complications/mental-health/stress.html |archive-date=12 November 2014}}</ref>
Regular exercise is crucial for maintaining overall health, though the effect of exercise on blood sugar can be challenging to predict.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Physical Activity and Exercise"}} Exogenous insulin can drive down blood sugar, leaving those with diabetes at risk of hypoglycemia during and immediately after exercise, then again seven to eleven hours after exercise (called the "lag effect").{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Physical Activity and Exercise"}} Conversely, high-intensity interval exercise (HIIT) can result in a shortage of insulin, and consequent hyperglycemia.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Physical Activity and Exercise"}} The risk of hypoglycemia can be managed by beginning exercise when blood sugar is relatively high (above 100 mg/dL or 5.5 mmol/L), ingesting carbohydrates during or shortly after exercise, and reducing the amount of injected insulin within two hours of the planned exercise.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Physical Activity and Exercise"}} 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.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Physical Activity and Exercise"}}
When focusing on the type of exercise, the first two studies explicitly focus on the role of exercise in managing diabetes, with the first study exploring the benefits of HIIT for psychological and physical health in T1DM and the second focusing on the effectiveness of exercise in T2DM.<ref name=":6">{{cite journal |last1=Alarcón-Gómez |first1=Jesús |last2=Chulvi-Medrano |first2=Iván |last3=Martin-Rivera |first3=Fernando |last4=Calatayud |first4=Joaquín |title=Effect of High-Intensity Interval Training on Quality of Life, Sleep Quality, Exercise Motivation and Enjoyment in Sedentary People with Type 1 Diabetes Mellitus |date=January 2021 |journal=International Journal of Environmental Research and Public Health |language=en |volume=18 |issue=23 |article-number=12612 |issn=1660-4601 |pmid=34886337 |doi=10.3390/ijerph182312612 |doi-access=free |pmc=8656786}}</ref><ref name=":7">{{cite journal |last=Lumb |first=Alistair |title=Diabetes and exercise |date=2014-12-01 |journal=Clinical Medicine |volume=14 |issue=6 |pages=673–676 |issn=1470-2118 |pmid=25468857 |doi=10.7861/clinmedicine.14-6-673 |pmc=4954144}}</ref> The third study, however, discusses the implications of diabetes misdiagnosis, which indirectly relates to exercise by stressing the importance of managing diabetes properly before engaging in physical activity.<ref name=":8">{{cite journal |last1=Tosur |first1=Mustafa |last2=Huang |first2=Xiaofan |last3=Inglis |first3=Audrey S. |last4=Aguirre |first4=Rebecca Schneider |last5=Redondo |first5=Maria J. |title=Inaccurate diagnosis of diabetes type in youth: prevalence, characteristics, and implications |date=2024-04-17 |journal=Scientific Reports |language=en |volume=14 |issue=1 |page=8876 |issn=2045-2322 |bibcode=2024NatSR..14.8876T |pmid=38632329 |doi=10.1038/s41598-024-58927-6 |pmc=11024140}}</ref> For the impacts that exercise has, the first and second studies highlight exercise as a beneficial tool for managing diabetes, but they present different outcomes.<ref name=":6"/><ref name=":7"/> In T2DM, exercise is shown to be a powerful tool for improving glycemic control and reducing cardiovascular risk. 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.<ref name=":7"/> The first study, however, finds that HIIT can still be effective in improving psychological well-being and exercise adherence for T1DM, showing that exercise has a broader benefit beyond just metabolic control.<ref name=":6"/> All three studies provide insight into the barriers to exercise in diabetes. The first study mentions fear of hypoglycemia and low motivation as challenges for T1DM, while the second reinforces the issue of blood sugar fluctuations and the unpredictability of exercise for those with T1DM.<ref name=":6"/><ref name=":7"/> The third study is more focused on the broader implications of misdiagnosis, but it implies that exercise could be counterproductive or harmful if a child's diabetes is misdiagnosed.<ref name=":8"/> When looking at other factors such as psychological and motivational, the first study places a strong emphasis on psychological factors like exercise enjoyment and intrinsic motivation, suggesting that overcoming psychological barriers is key to exercise adherence in T1DM.<ref name=":6"/> In contrast, the second study is more focused on the physical and metabolic effects of exercise, with less emphasis on motivation or enjoyment, although it does briefly mention that many individuals with T1DM are still motivated to exercise by the health benefits or inspiration from others.<ref name=":7"/> Clinical implications show the first two studies focus on the effectiveness of exercise for specific diabetes types, while the third study highlights the importance of correct diagnosis for appropriate care.<ref name=":6"/><ref name=":8"/><ref name=":7"/> This suggests that exercise programs must be tailored not only to the type of diabetes but also to the individual's health status and management plan. The third study emphasizes that without proper diagnosis and management, exercise recommendations could be inappropriate or unsafe.<ref name=":8"/> In summary, while the first two studies explore the benefits and challenges of exercise in different diabetes types, the third study stresses the importance of accurate diagnosis and management before engaging in physical activity. Together, these studies highlight the complex interactions between exercise, diabetes type, treatment, and individual challenges.
===Transplant===
In some cases, people can receive transplants of the pancreas or isolated islet cells to restore insulin production and alleviate diabetic symptoms. Transplantation of the whole pancreas is rare, due in part to the few available donor organs, and to the need for lifelong immunosuppressive therapy to prevent transplant rejection.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Pancreas and Islet Cell Transplantation"}}<ref name=ADA-Transplant>{{cite journal |vauthors=Robertson RP, Davis C, Larsen J, Stratta R, Sutherland DE |title=Pancreas and islet transplantation in type 1 diabetes |journal=Diabetes Care |volume=29 |issue=4 |page=935 |date=April 2006 |pmid=16567844 |doi=10.2337/diacare.29.04.06.dc06-9908 |doi-access=free}}</ref> The American Diabetes Association recommends pancreas transplantation only in people who also require a kidney transplant, or who struggle to perform regular insulin therapy and experience repeated severe side effects of poor blood sugar control.<ref name=ADA-Transplant/> Most pancreas transplants are done simultaneously with a kidney transplant, with both organs from the same donor.{{sfn|Dean|Kukla|Stegall|Kudva|2017|loc="Simultaneous pancreas-kidney transplant"}} The transplanted pancreas continues to function for at least five years in around three-quarters of recipients, allowing them to stop taking insulin.{{sfn|Dean|Kukla|Stegall|Kudva|2017|loc="Outcomes of pancreas transplantation"}}
Transplantations of islets alone have become increasingly common.{{sfn|Shapiro|Pokrywczynska|Ricordi|2017|loc="Main"}} Pancreatic islets are isolated from a donor pancreas, then injected into the recipient's portal vein from which they implant onto the recipient's liver.{{sfn|Rickels|Robertson|2019|loc="Islet allotransplantation for the treatment of type 1 diabetes"}} In nearly half of recipients, the islet transplant continues to work well enough that they still do not need exogenous insulin five years after transplantation.{{sfn|Rickels|Robertson|2019|loc="Long-term outcomes and comparison with pancreas transplantation"}} If a transplant fails, recipients can receive subsequent injections of islets from additional donors into the portal vein.{{sfn|Rickels|Robertson|2019|loc="Islet allotransplantation for the treatment of type 1 diabetes"}} Like with whole pancreas transplantation, islet transplantation requires lifelong immunosuppression and depends on the limited supply of donor organs; it is therefore similarly limited to people with severe poorly controlled diabetes and those who have had or are scheduled for a kidney transplant.{{sfn|Shapiro|Pokrywczynska|Ricordi|2017|loc="Main"}}{{sfn|Shapiro|Pokrywczynska|Ricordi|2017|loc="Indications for islet transplantation"}}
A novel approach by Sana Biotechnology is hypo-immune donor-derived islets, which are genetically engineered (B2M−/−, CIITA−/−, CD47+) to be invisible to the immune system, thereby eliminating the need for immunosuppressants. Cadaveric donor islets are dispersed, and CRISPR/Cas 9 is used to disrupt the B2M and CIITA genes, and CD47 transduction is performed using a Lentiviral Vector (LVV). The successfully engineered islet cells are then reclustered to form pseudoislets.<ref>{{Cite journal |last=Hu |first=Xiaomeng |last2=White |first2=Kathy |last3=Young |first3=Chi |last4=Olroyd |first4=Ari G. |last5=Kievit |first5=Paul |last6=Connolly |first6=Andrew J. |last7=Deuse |first7=Tobias |last8=Schrepfer |first8=Sonja |date=2024-03-07 |title=Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate |url=https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00044-4 |journal=Cell Stem Cell |language=English |volume=31 |issue=3 |pages=334–340.e5 |doi=10.1016/j.stem.2024.02.001 |issn=1934-5909 |pmid=38335966}}</ref> In 2025, the first person with T1D was reported to receive a successful transplant of hypoimmune islets. The islets produced insulin without the patient's need to take immunosuppressants.<ref>{{Cite journal |last=Carlsson |first=Per-Ola |last2=Hu |first2=Xiaomeng |last3=Scholz |first3=Hanne |last4=Ingvast |first4=Sofie |last5=Lundgren |first5=Torbjörn |last6=Scholz |first6=Tim |last7=Eriksson |first7=Olof |last8=Liss |first8=Per |last9=Yu |first9=Di |last10=Deuse |first10=Tobias |last11=Korsgren |first11=Olle |last12=Schrepfer |first12=Sonja |date=2025-09-04 |title=Survival of Transplanted Allogeneic Beta Cells with No Immunosuppression |url=http://www.nejm.org/doi/10.1056/NEJMoa2503822 |journal=New England Journal of Medicine |language=en |volume=393 |issue=9 |pages=887–894 |doi=10.1056/NEJMoa2503822 |issn=0028-4793}}</ref>
Donislecel (Lantidra) allogeneic (donor) pancreatic islet cellular therapy was approved for medical use in the United States in June 2023.<ref name="FDA PR 20230628">{{cite press release |title=FDA Approves First Cellular Therapy to Treat Patients with Type 1 Diabetes |date=28 June 2023 |website=U.S. Food and Drug Administration (FDA) |url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-type-1-diabetes |access-date=28 June 2023}} {{Source-attribution}}</ref>
=== Continuous Glucose Monitoring === Continuous glucose monitoring (CGM) is a method of monitoring blood glucose levels using a wearable sensor that provides real-time measurements including glucose management index, time in range, time in hypoglycemia, time in hyperglycemia, and glucose variability<ref>{{Citation |last=Bergenstal |first=Richard M. |title=Understanding Continuous Glucose Monitoring Data |date=2018 |work=Role of Continuous Glucose Monitoring in Diabetes Treatment |url=http://www.ncbi.nlm.nih.gov/books/NBK538967/ |access-date=2026-03-21 |series=ADA Clinical Compendia Series |place=Arlington (VA) |publisher=American Diabetes Association |pmid=34251769}}</ref>. CGM has been found to offer improved glycemic control, which reduces hypogylcemic events and diabetic emergencies<ref>{{Cite journal |last=Manov |first=Andre E. |last2=Chauhan |first2=Sukhjinder |last3=Dhillon |first3=Gundip |last4=Dhaliwal |first4=Athena |last5=Antonio |first5=Sabrina |last6=Donepudi |first6=Ashrita |last7=Jalal |first7=Yema N. |last8=Nazha |first8=Jonathan |last9=Banal |first9=Melissa |last10=House |first10=Joseph |date=July 2023 |title=The Effectiveness of Continuous Glucose Monitoring Devices in Managing Uncontrolled Diabetes Mellitus: A Retrospective Study |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC10460137/ |journal=Cureus |volume=15 |issue=7 |article-number=e42545 |doi=10.7759/cureus.42545 |doi-access=free|issn=2168-8184 |pmc=10460137 |pmid=37637581}}</ref>. In 2016, the American Diabetes Association (ADA) broadly recommended the use of CGM for individuals with Type 1 diabetes and currently around 49.78% of patients utilize the technology<ref>{{Cite journal |last=Lacy |first=Mary E. |last2=Lee |first2=Katherine E. |last3=Atac |first3=Omer |last4=Heier |first4=Kory |last5=Fowlkes |first5=John |last6=Kucharska-Newton |first6=Anna |last7=Moga |first7=Daniela C. |date=2024-01-19 |title=Patterns and Trends in Continuous Glucose Monitoring Utilization Among Commercially Insured Individuals With Type 1 Diabetes: 2010–2013 to 2016–2019 |url=https://diabetesjournals.org/clinical/article/42/3/388/154160/Patterns-and-Trends-in-Continuous-Glucose |journal=Clinical Diabetes |language=en |volume=42 |issue=3 |pages=388–397 |doi=10.2337/cd23-0051 |issn=0891-8929 |archive-url=http://web.archive.org/web/20251130070552/https://diabetesjournals.org/clinical/article/42/3/388/154160/Patterns-and-Trends-in-Continuous-Glucose |archive-date=2025-11-30}}</ref>.
==Pathogenesis== Type 1 diabetes is a result of the destruction of pancreatic beta cells, although what triggers that destruction remains unclear.{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="The immune phenotype of type 1 diabetes"}} People with type 1 diabetes tend to have more CD8+ T-cells and B-cells that specifically target islet antigens than those without type 1 diabetes, suggesting a role for the adaptive immune system in beta cell destruction.{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="The immune phenotype of type 1 diabetes"}}{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="Diagnosis"}} Type 1 diabetics also tend to have reduced regulatory T cell function, which may exacerbate autoimmunity.{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="The immune phenotype of type 1 diabetes"}} Destruction of beta cells results in inflammation of the islet of Langerhans, called insulitis. These inflamed islets tend to contain CD8+ T-cells and – to a lesser extent – CD4+ T cells.{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="The immune phenotype of type 1 diabetes"}} Abnormalities in the pancreas or the beta cells themselves may also contribute to beta-cell destruction. The pancreases of people with type 1 diabetes tend to be smaller, lighter, and have abnormal blood vessels, nerve innervations, and extracellular matrix organization.{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="The β-cell phenotype of type 1 diabetes"}} 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.{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="The β-cell phenotype of type 1 diabetes"}}
The mechanism by which the beta cells actually die likely involves both necroptosis and apoptosis, induced or exacerbated by CD8+ T-cells and macrophages.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Mechanisms of Beta-Cell Death in T1DM"}} 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.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Mechanisms of Beta-Cell Death in T1DM"}} As some beta cells die, they may release cellular components that amplify the immune response, exacerbating inflammation and cell death.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Mechanisms of Beta-Cell Death in T1DM"}} Pancreases from people with type 1 diabetes also have signs of beta cell apoptosis, linked to activation of the janus kinase and TYK2 pathways.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Mechanisms of Beta-Cell Death in T1DM"}}
Partial ablation of beta-cell function is enough to cause diabetes; at diagnosis, people with type 1 diabetes often still have detectable beta-cell function. Once insulin therapy is started, many people experience a resurgence in beta-cell function, and can go some time with little-to-no insulin treatment – called the "honeymoon phase".{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="The β-cell phenotype of type 1 diabetes"}} This eventually fades as beta-cells continue to be destroyed, and insulin treatment is required again.{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="The β-cell phenotype of type 1 diabetes"}} Beta-cell destruction is not always complete, as 30–80% of type 1 diabetics produce small amounts of insulin years or decades after diagnosis.{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="The β-cell phenotype of type 1 diabetes"}}
===Alpha cell dysfunction=== Onset of autoimmune diabetes is accompanied by impaired ability to regulate the hormone glucagon,<ref name="Farhy_2015">{{cite journal |vauthors=Farhy LS, McCall AL |title=Glucagon – the new 'insulin' in the pathophysiology of diabetes |journal=Current Opinion in Clinical Nutrition and Metabolic Care |volume=18 |issue=4 |pages=407–414 |date=July 2015 |pmid=26049639 |doi=10.1097/mco.0000000000000192 |s2cid=19872862}}</ref> which acts in antagonism with insulin to regulate blood sugar and metabolism. 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 hypoglycemia prevents a glucagon-mediated rescue of glucose levels.<ref name="Yosten_2018">{{cite journal |vauthors=Yosten GL |title=Alpha cell dysfunction in type 1 diabetes |journal=Peptides |volume=100 |pages=54–60 |date=February 2018 |pmid=29412832 |doi=10.1016/j.peptides.2017.12.001 |s2cid=46878644}}</ref>
====Hyperglucagonemia==== The 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%.<ref>{{cite journal |vauthors=Brown RJ, Sinaii N, Rother KI |title=Too much glucagon, too little insulin: time course of pancreatic islet dysfunction in new-onset type 1 diabetes |journal=Diabetes Care |volume=31 |issue=7 |pages=1403–1404 |date=July 2008 |pmid=18594062 |doi=10.2337/dc08-0575 |pmc=2453684}}</ref> Insulin production will continue to fall as the immune system destroys beta cells, 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 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.<ref name="Yosten_2018"/> Some researchers believe glucagon dysregulation to be the primary cause of early-stage hyperglycemia.<ref>{{cite journal |vauthors=Unger RH, Cherrington AD |title=Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover |journal=The Journal of Clinical Investigation |volume=122 |issue=1 |pages=4–12 |date=January 2012 |pmid=22214853 |doi=10.1172/JCI60016 |pmc=3248306}}</ref> 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.<ref>{{cite journal |vauthors=Meier JJ, Kjems LL, Veldhuis JD, Lefèbvre P, Butler PC |title=Postprandial suppression of glucagon secretion depends on intact pulsatile insulin secretion: further evidence for the intraislet insulin hypothesis |journal=Diabetes |volume=55 |issue=4 |pages=1051–1056 |date=April 2006 |pmid=16567528 |doi=10.2337/diabetes.55.04.06.db05-1449 |doi-access=free}}</ref><ref>{{cite journal |vauthors=Cooperberg BA, Cryer PE |title=Beta-cell-mediated signaling predominates over direct alpha-cell signaling in the regulation of glucagon secretion in humans |journal=Diabetes Care |volume=32 |issue=12 |pages=2275–2280 |date=December 2009 |pmid=19729529 |doi=10.2337/dc09-0798 |pmc=2782990}}</ref> Under this working hypothesis intensive insulin therapy has attempted to mimic natural insulin secretion profiles in exogenous insulin infusion therapies.<ref>{{cite journal |vauthors=Paolisso G, Sgambato S, Torella R, Varricchio M, Scheen A, D'Onofrio F, Lefèbvre PJ |title=Pulsatile insulin delivery is more efficient than continuous infusion in modulating islet cell function in normal subjects and patients with type 1 diabetes |journal=The Journal of Clinical Endocrinology and Metabolism |volume=66 |issue=6 |pages=1220–1226 |date=June 1988 |pmid=3286673 |doi=10.1210/jcem-66-6-1220}}</ref> In young people with type 1 diabetes, unexplained deaths could be due to nighttime hypoglycemia triggering abnormal heart rhythms or cardiac autonomic neuropathy, damage to nerves that control the function of the heart.
====Hypoglycemic glucagon impairment==== Glucagon secretion is normally increased upon falling glucose levels, but normal glucagon response to hypoglycemia is blunted in type 1 diabetics.<ref name="Banarer_2002">{{cite journal |vauthors=Banarer S, McGregor VP, Cryer PE |title=Intraislet hyperinsulinemia prevents the glucagon response to hypoglycemia despite an intact autonomic response |journal=Diabetes |volume=51 |issue=4 |pages=958–965 |date=April 2002 |pmid=11916913 |doi=10.2337/diabetes.51.4.958 |doi-access=free}}</ref><ref>{{cite journal |vauthors=Raju B, Cryer PE |title=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 |journal=Diabetes |volume=54 |issue=3 |pages=757–764 |date=March 2005 |pmid=15734853 |doi=10.2337/diabetes.54.3.757 |doi-access=free}}</ref> Beta cell glucose sensing and subsequent suppression of administered insulin secretion is absent, leading to islet hyperinsulinemia which inhibits glucagon release.<ref name="Banarer_2002"/><ref name="Tesfaye_2010">{{cite journal |vauthors=Tesfaye N, Seaquist ER |title=Neuroendocrine responses to hypoglycemia |journal=Annals of the New York Academy of Sciences |volume=1212 |issue=1 |pages=12–28 |date=November 2010 |bibcode=2010NYASA1212...12T |pmid=21039590 |doi=10.1111/j.1749-6632.2010.05820.x |pmc=2991551}}</ref>
Autonomic inputs to alpha cells are far more important for glucagon stimulation in the moderate to severe ranges of hypoglycemia, yet the autonomic response is blunted in several ways. Recurrent hypoglycemia leads to metabolic adjustments in the glucose-sensing areas of the brain, shifting the threshold for counterregulatory activation of the sympathetic nervous system to lower glucose concentration.<ref name="Tesfaye_2010"/> This is known as hypoglycemic unawareness. Subsequent hypoglycemia is met with impairment in the 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. A consensus has yet to be reached.<ref name="Reno_2013">{{cite journal |vauthors=Reno CM, Litvin M, Clark AL, Fisher SJ |title=Defective counterregulation and hypoglycemia unawareness in diabetes: mechanisms and emerging treatments |journal=Endocrinology and Metabolism Clinics of North America |volume=42 |issue=1 |pages=15–38 |date=March 2013 |pmid=23391237 |doi=10.1016/j.ecl.2012.11.005 |pmc=3568263}}</ref> The major hypotheses are summarized in the following table:<ref>{{cite journal |vauthors=Martín-Timón I, Del Cañizo-Gómez FJ |title=Mechanisms of hypoglycemia unawareness and implications in diabetic patients |journal=World Journal of Diabetes |volume=6 |issue=7 |pages=912–926 |date=July 2015 |pmid=26185599 |doi=10.4239/wjd.v6.i7.912 |doi-access=free |pmc=4499525}}</ref><ref name="Tesfaye_2010"/><ref name="Reno_2013"/> {| class="wikitable" | colspan="2" |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 relieve oxidative stress that would activate the sympathetic response. |- |Alternative fuel hypothesis |Decreased reliance on glucose, supplementation of lactate from astrocytes, or ketones meet metabolic demands and reduce stress to the 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.<ref name="Mundinger_2016">{{cite journal |vauthors=Mundinger TO, Taborsky GJ |title=Early sympathetic islet neuropathy in autoimmune diabetes: lessons learned and opportunities for investigation |journal=Diabetologia |volume=59 |issue=10 |pages=2058–2067 |date=October 2016 |pmid=27342407 |doi=10.1007/s00125-016-4026-0 |pmc=6214182}}</ref> This loss constitutes an 80–90% reduction of islet sympathetic nerve endings, happens early in the progression of the disease, and is persistent through the life of the patient.<ref>{{cite journal |vauthors=Mundinger TO, Mei Q, Foulis AK, Fligner CL, Hull RL, Taborsky GJ |title=Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves |journal=Diabetes |volume=65 |issue=8 |pages=2322–2330 |date=August 2016 |pmid=27207540 |doi=10.2337/db16-0284 |pmc=4955989}}</ref> 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 the islet sympathetic nerves. Increased BDNF and ROS that result from insulitis and beta cell death stimulate the p75 neurotrophin receptor (p75<sup>NTR</sup>), 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.<ref name="Mundinger_2016"/>
==Complications== {{Main|Complications of diabetes}}
The most pressing complications of type 1 diabetes are the always-present risks of poor blood sugar control: severe hypoglycemia and diabetic ketoacidosis. Hypoglycemia – typically blood sugar below 70 mg/dL (3.9 mmol/L) – triggers the release of epinephrine, and can cause people to feel shaky, anxious, or irritable.<ref name=ADAHypo>{{cite web |title=Hypoglycemia (Low blood sugar) |publisher=American Diabetes Association |url=https://www.diabetes.org/healthy-living/medication-treatments/blood-glucose-testing-and-control/hypoglycemia |access-date=20 March 2022}}</ref> People with hypoglycemia may also experience hunger, nausea, sweats, chills, headaches, dizziness, and a fast heartbeat.<ref name=ADAHypo/> Some feel lightheaded, sleepy, or weak.<ref name=ADAHypo/> Severe hypoglycemia can develop rapidly, causing confusion, coordination problems, loss of consciousness, and seizure.<ref name=ADAHypo/>{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2455}} On average, people with type 1 diabetes experience a hypoglycemia event that requires assistance of another 16–20 times in 100 person-years, and an event leading to unconsciousness or seizure 2–8 times per 100 person-years.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2455}} The American Diabetes Association recommends treating hypoglycemia by the "15–15 rule": eat 15 grams of carbohydrates, then wait 15 minutes before checking blood sugar; repeat until blood sugar is at least 70 mg/dL (3.9 mmol/L).<ref name=ADAHypo/> 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.<ref name=ADAHypo/> People with repeated bouts of hypoglycemia can develop hypoglycemia unawareness, where the blood sugar threshold at which they experience symptoms of hypoglycemia decreases, increasing their risk of severe hypoglycemic events.{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="Complications of type 1 diabetes"}} Rates of severe hypoglycemia have generally declined due to the advent of rapid-acting and long-acting insulin products in the 1990s and early 2000s;{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Insulin Therapy"}} however, acute hypoglycemia still causes 4–10% of type 1 diabetes-related deaths.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2455}}
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.<ref name=ADA-Keto/> Ketoacidosis symptoms can develop rapidly, with frequent urination, excessive thirst, nausea, vomiting, and severe abdominal pain all common.{{sfn|Cashen|Petersen|2019|loc="Diagnosis, screening, and prevention"}} More severe ketoacidosis can result in labored breathing, and loss of consciousness due to cerebral edema.{{sfn|Cashen|Petersen|2019|loc="Diagnosis, screening, and prevention"}} People with type 1 diabetes experience diabetic ketoacidosis 1–5 times per 100 person-years, the majority of which result in hospitalization.{{sfn|Cashen|Petersen|2019|loc="Epidemiology"}} 13–19% of type 1 diabetes-related deaths are caused by ketoacidosis,{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2455}} making ketoacidosis the leading cause of death in people with type 1 diabetes less than 58 years old.{{sfn|Cashen|Petersen|2019|loc="Epidemiology"}}
===Long-term complications=== <!--Microvascular complications: retinopathy, neuropathy, nephropathy (maybe also cognitive function, et al); all controlled by hyperglycemia. Macrovascular complications: atherosclerosis and thrombosis in the heart, brain, or peripheral arteries. Less controlled by blood sugar.--> 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.{{sfn|DiMeglio|Evans-Molina|Oram|2018|loc="Complications of type 1 diabetes"}} In the eyes, prolonged high blood sugar causes the blood vessels in the retina to become fragile.{{sfn|Brownlee|Aiello|Sun|Cooper|2020|loc="Pathophysiology of diabetic retinopathy"}}
People with type 1 diabetes also have an increased risk of cardiovascular disease, which is estimated to shorten the life of the average type 1 diabetic by 8–13 years.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2456}} Cardiovascular disease<ref name="pmid16505242">{{cite journal |vauthors=Devaraj S, Glaser N, Griffen S, Wang-Polagruto J, Miguelino E, Jialal I |title=Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes |journal=Diabetes |volume=55 |issue=3 |pages=774–779 |date=March 2006 |pmid=16505242 |doi=10.2337/diabetes.55.03.06.db05-1417 |doi-access=free}}</ref> as well as neuropathy<ref name="pmid16043739">{{cite journal |vauthors=Granberg V, Ejskjaer N, Peakman M, Sundkvist G |title=Autoantibodies to autonomic nerves associated with cardiac and peripheral autonomic neuropathy |journal=Diabetes Care |volume=28 |issue=8 |pages=1959–1964 |date=August 2005 |pmid=16043739 |doi=10.2337/diacare.28.8.1959 |doi-access=free}}</ref> 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.<ref>{{cite journal |vauthors=Huxley RR, Peters SA, Mishra GD, Woodward M |title=Risk of all-cause mortality and vascular events in women versus men with type 1 diabetes: a systematic review and meta-analysis |journal=The Lancet. Diabetes & Endocrinology |volume=3 |issue=3 |pages=198–206 |date=March 2015 |pmid=25660575 |doi=10.1016/S2213-8587(14)70248-7|hdl=20.500.11937/15312 |hdl-access=free }}</ref>
About 12 percent of people with type 1 diabetes have clinical depression.<ref name="Roy, T. 2012">{{cite journal |vauthors=Roy T, Lloyd CE |title=Epidemiology of depression and diabetes: a systematic review |journal=Journal of Affective Disorders |volume=142 |issue=Suppl |pages=S8–21 |date=October 2012 |pmid=23062861 |doi=10.1016/S0165-0327(12)70004-6}}</ref> About 6 percent of people with type 1 diabetes also have celiac disease, but in most cases there are no digestive symptoms<ref name=ElfstromSundstrom2014>{{cite journal |vauthors=Elfström P, Sundström J, Ludvigsson JF |title=Systematic review with meta-analysis: associations between coeliac disease and type 1 diabetes |journal=Alimentary Pharmacology & Therapeutics |volume=40 |issue=10 |pages=1123–1132 |date=November 2014 |pmid=25270960 |doi=10.1111/apt.12973 |doi-access=free |s2cid=25468009}}</ref><ref name=SeeKaukinen2015>{{cite journal |vauthors=See JA, Kaukinen K, Makharia GK, Gibson PR, Murray JA |title=Practical insights into gluten-free diets |journal=Nature Reviews. Gastroenterology & Hepatology |volume=12 |issue=10 |pages=580–591 |date=October 2015 |type=Review |pmid=26392070 |doi=10.1038/nrgastro.2015.156 |s2cid=20270743 |quote=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}}</ref> or are mistakenly attributed to poor control of diabetes, gastroparesis, or diabetic neuropathy.<ref name=SeeKaukinen2015/> In most cases, celiac disease is diagnosed after the 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.<ref name=ElfstromSundstrom2014/>
===Urinary tract infection=== People with diabetes show an increased rate of urinary tract infection.<ref>{{cite journal |vauthors=Chen HS, Su LT, Lin SZ, Sung FC, Ko MC, Li CY |title=Increased risk of urinary tract calculi among patients with diabetes mellitus – a population-based cohort study |journal=Urology |volume=79 |issue=1 |pages=86–92 |date=January 2012 |pmid=22119251 |doi=10.1016/j.urology.2011.07.1431}}</ref> The reason is that bladder dysfunction is more common in people with diabetes than in 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.<ref>{{cite journal |vauthors=James R, Hijaz A |title=Lower urinary tract symptoms in women with diabetes mellitus: a current review |journal=Current Urology Reports |volume=15 |issue=10 |article-number=440 |date=October 2014 |pmid=25118849 |doi=10.1007/s11934-014-0440-3 |s2cid=30653959}}</ref>
===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.<ref name="Sexual Dysfunction in Women">{{cite web |title=Sexual Dysfunction in Women |publisher=Diabetes Digital Media Ltd |website=Diabetes.co.uk |url=https://www.diabetes.co.uk/sexual-dysfunction-in-women.html |access-date=28 November 2014 |url-status=live |archive-url=https://web.archive.org/web/20141109021341/http://www.diabetes.co.uk/sexual-dysfunction-in-women.html |archive-date=9 November 2014}}</ref> 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.<ref>{{cite journal |vauthors=Goswami SK, Vishwanath M, Gangadarappa SK, Razdan R, Inamdar MN |title=Efficacy of ellagic acid and sildenafil in diabetes-induced sexual dysfunction |journal=Pharmacognosy Magazine |volume=10 |issue=Suppl 3 |pages=S581–S587 |date=August 2014 |pmid=25298678 |doi=10.4103/0973-1296.139790 |doi-access=free |pmc=4189276 |id={{ProQuest|1610759650}}}}</ref> Sexual problems are common in women who have diabetes,<ref name="Sexual Dysfunction in Women"/> 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.<ref name="Sexual Dysfunction in Women"/>
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.<ref name="Sexual Dysfunction in Women"/>
Women with type 1 diabetes show a higher than normal rate of polycystic ovarian syndrome (PCOS).<ref>{{cite journal |vauthors=Escobar-Morreale HF, Roldán B, Barrio R, Alonso M, Sancho J, de la Calle H, García-Robles R |title=High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus |journal=The Journal of Clinical Endocrinology and Metabolism |volume=85 |issue=11 |pages=4182–4187 |date=November 2000 |pmid=11095451 |doi=10.1210/jcem.85.11.6931 |doi-access=free}}</ref> The reason may be that the ovaries are exposed to high insulin concentrations since women with type 1 diabetes can have frequent hyperglycemia.<ref>{{cite journal |vauthors=Codner E, Escobar-Morreale HF |title=Clinical review: Hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus |journal=The Journal of Clinical Endocrinology and Metabolism |volume=92 |issue=4 |pages=1209–1216 |date=April 2007 |pmid=17284617 |doi=10.1210/jc.2006-2641 |doi-access=free}}</ref>
===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 respectively.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Other Complications"}}{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2455}} 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.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Other Complications"}} Type 1 diabetics are also at increased risk of rheumatoid arthritis, lupus, autoimmune gastritis, pernicious anemia, vitiligo, and Addison's disease.{{sfn|DiMeglio|Evans-Molina|Oram|2018|p=2455}} 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.{{sfn|Redondo|Steck|Pugliese|2018|loc="Evidence for the contribution of genetics to type I diabetes"}}
==Prevention== There is ongoing research for methods to prevent type 1 diabetes.<ref>{{cite web |title=What is Type 1 Diabetes? |url=https://www.nhs.uk/conditions/type-1-diabetes/what-is-type-1-diabetes/ |publisher=National Health Service (NHS) |date=31 October 2024 |access-date=28 October 2025}}</ref> 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.<ref>{{cite web |title=FDA Approves Tzield |publisher=Drugs.com |date=November 2022 |url=https://www.drugs.com/newdrugs/fda-approves-tzield-teplizumab-mzwv-delay-onset-stage-3-type-1-diabetes-5929.html |access-date=15 February 2023}}</ref>
In addition to anti-CD3 antibodies, several other immunosuppressive agents have been trialled to prevent 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.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Immunosuppresion"}} Several other immunosuppressive agents – prednisone, azathioprine, anti-thymocyte globulin, mycophenolate, and antibodies against CD20 and IL2 receptor α – have been the subject of research. None has provided lasting protection from the development of type 1 diabetes.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Immunosuppresion"}} 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.{{sfn|von Scholten|Kreiner|Gough|von Herrath|2021|loc="Antigen vaccination"}}
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.{{sfn|Dayan|Korah|Tatovic|Bundy|2019|loc="Previous prevention trials"}} Similarly, trials that gave high-risk individuals injected insulin, oral insulin, or nicotinamide did not prevent diabetes development.{{sfn|Dayan|Korah|Tatovic|Bundy|2019|loc="Previous prevention trials"}}
Other strategies under investigation for the prevention of type 1 diabetes include gene therapy, stem cell therapy, and modulation of the gut microbiome. Gene therapy approaches are still in early stages. They aim to alter genetic factors that contribute to beta-cell destruction by editing immune responses.<ref>{{cite journal |last1=Chellappan |first1=Dinesh Kumar |last2=Sivam |first2=Nandhini S. |last3=Teoh |first3=Kai Xiang |last4=Leong |first4=Wai Pan |last5=Fui |first5=Tai Zhen |last6=Chooi |first6=Kien |last7=Khoo |first7=Nico |last8=Yi |first8=Fam Jia |last9=Chellian |first9=Jestin |last10=Cheng |first10=Lim Lay |last11=Dahiya |first11=Rajiv |last12=Gupta |first12=Gaurav |last13=Singhvi |first13=Gautam |last14=Nammi |first14=Srinivas |last15=Hansbro |first15=Philip Michael |title=Gene therapy and type 1 diabetes mellitus |date=2018-12-01 |journal=Biomedicine & Pharmacotherapy |volume=108 |pages=1188–1200 |issn=0753-3322 |pmid=30372820 |doi=10.1016/j.biopha.2018.09.138 |doi-access=free}}</ref> Stem cell therapies are also being researched, with the hope that they can either regenerate insulin-producing beta cells or protect them from immune attack.<ref>{{cite journal |title=Current progress in stem cell therapy for type 1 diabetes mellitus |date=2020 |journal=Stem Cell Research & Therapy |volume=11 |issue=1 |article-number=275 |vauthors=Chen S, Du K, Zou C |pmid=32641151 |doi=10.1186/s13287-020-01793-6 |doi-access=free |pmc=7346484}}</ref> Trials using stem cells to restore beta cell function or regulate immune responses are ongoing.
Modifying the gut microbiota through the use of probiotics, prebiotics, or specific diets has also gained attention. Some evidence suggests that the gut microbiome plays a role in immune regulation, and researchers are investigating whether altering the microbiome could reduce the risk of autoimmunity and, subsequently, type 1 diabetes.<ref>{{cite journal |last=Vaarala |first=Outi |title=Gut microbiota and type 1 diabetes |date=2012 |journal=The Review of Diabetic Studies |volume=9 |issue=4 |pages=251–259 |issn=1614-0575 |pmid=23804264 |doi=10.1900/RDS.2012.9.251 |doi-broken-date=12 July 2025 |pmc=3740694}}</ref>
Tolerogenic therapies, which seek to induce immune tolerance to beta-cell antigens, are another area of interest. Techniques such as using dendritic cells or regulatory T cells engineered to promote tolerance to beta cells are being studied in clinical trials, though these approaches remain experimental.<ref>{{cite journal |last1=Bluestone |first1=Jeffrey A. |last2=Herold |first2=Kevan |last3=Eisenbarth |first3=George |title=Genetics, pathogenesis and clinical interventions in type 1 diabetes |date=2010-04-29 |journal=Nature |volume=464 |issue=7293 |pages=1293–1300 |issn=1476-4687 |bibcode=2010Natur.464.1293B |pmid=20432533 |doi=10.1038/nature08933 |pmc=4959889}}</ref>
There is evidence suggesting that certain viral infections may trigger type 1 diabetes.<ref>{{cite journal |title=Viruses and Type 1 Diabetes: From Enteroviruses to the Virome |date=2021 |journal=Microorganisms |volume=9 |issue=7 |page=1519 |vauthors=Isaacs SR, Foskett DB, Maxwell AJ, Ward EJ, Faulkner CL, Luo JY, Rawlinson WD, Craig ME, Kim KW |pmid=34361954 |doi=10.3390/microorganisms9071519 |doi-access=free |pmc=8306446}}</ref> Systematic review and meta-analyses of 60 studies indicated that exposure to enteroviruses increases the risk.<ref>{{cite journal |vauthors=Isaacs SR, Roy A, Dance B, Ward EJ, Foskett DB, Maxwell AJ, Rawlinson WD, Kim KW, Craig ME |title=Enteroviruses and risk of islet autoimmunity or type 1 diabetes: systematic review and meta-analysis of controlled observational studies detecting viral nucleic acids and proteins |date=2023 |journal=The Lancet Diabetes & Endocrinology |volume=11 |issue=8 |pages=578–592 |doi=10.1016/S2213-8587(23)00122-5 |pmid=37390839}}</ref> Enterovirus B, Enterovirus C, coxsackievirus B1, and coxsackievirus B4 were associated with elevated risk. Infections during pregnancy have also been associated with an increased risk of type 1 diabetes in the offspring, with enteroviruses <ref>{{cite journal |vauthors=Allen DW, Kim KW, Rawlinson WD, Craig ME |title=Maternal virus infections in pregnancy and type 1 diabetes in their offspring: Systematic review and meta-analysis of observational studies |date=2018 |journal=Reviews in Medical Virology |volume=28 |issue=3 |article-number=e1974 |doi=10.1002/rmv.1974 |pmid=29569297}}</ref><ref>{{cite journal |vauthors=Yue Y, Tang Y, Tang J, Shi J, Zhu T, Huang J, Qiu X, Zeng Y, Li W, Qu Y, Mu D |title=Maternal infection during pregnancy and type 1 diabetes mellitus in offspring: a systematic review and meta-analysis |date=2018 |journal=Epidemiology & Infection |volume=146 |issue=16 |pages=2131–2138 |doi=10.1017/S0950268818002455 |pmid=30152300 |pmc=6453004 }}</ref>, rubella virus <ref>{{cite journal |vauthors=Rogers MA, Kim C |title= Congenital infections as contributors to the onset of diabetes in children: A longitudinal study in the United States, 2001-2017 |journal=Pediatric Diabetes |date=2020 |volume=21 |issue=3 |pages=456–459 |doi=10.1111/pedi.12957 |pmid=31820549 |pmc= 10545449 }}</ref><ref>{{cite journal |vauthors= Ginsberg-Fellner F, Witt ME, Fedun B, Taub F, Dobersen MJ, McEvoy RC, Cooper LZ, Notkins AL, Rubinstein P |title=Diabetes mellitus and autoimmunity in patients with the congenital rubella syndrome |journal=Reviews of Infectious Diseases |date=1985 |volume=7 Suppl 1 |pages=S170-176 |doi=10.1093/clinids/7.supplement_1.s170 |pmid=3890104}}</ref> , and cytomegalovirus <ref>{{cite journal |vauthors=Rogers MA, Kim C |title= Congenital infections as contributors to the onset of diabetes in children: A longitudinal study in the United States, 2001-2017 |journal=Pediatric Diabetes |date=2020 |volume=21 |issue=3 |pages=456–459 |doi=10.1111/pedi.12957 |pmid=31820549 |pmc= 10545449 }}</ref> showing elevated risk. Vaccination against rotavirus in young children has been associated with a reduction in incidence rates of type 1 diabetes.<ref>{{cite journal |vauthors=Kosmeri C, Klapas A, Evripidou N, Kantza E, Serbis A, Siomou E, Ladomenou F |title=Rotavirus Vaccination Protects Against Diabetes Mellitus Type 1 in Children in Developed Countries: A Systematic Review and Meta-Analysis |journal=Vaccines |date=2025 |volume=13 |issue=1 |page=50 |doi=10.3390/vaccines13010050 |doi-access=free |pmid=39852829 |pmc=11769441 }}</ref> Countries that implemented a nationwide rotavirus vaccination program have shown a decline in the incidence of type 1 diabetes in young children (<5 years of age)<ref>{{cite journal |vauthors=Rogers MA |title=Decline in Type 1 Diabetes in Young Children After Rotavirus Vaccination: Data From 8 Countries |journal=American Journal of Preventive Medicine Focus |date=2025 |volume=4 |issue=6 |article-number=100409 |doi=10.1016/j.focus.2025.100409 | pmid=41078994 |pmc=12508837 }}</ref> The results were more marked with the pentavalent rotavirus vaccine than the monovalent vaccine.<ref>{{cite journal |vauthors=Rogers MA |title=Decline in Type 1 Diabetes in Young Children After Rotavirus Vaccination: Data From 8 Countries |journal=American Journal of Preventive Meicine Focus |date=2025 |volume=4 |issue=6 |article-number=100409 |doi=10.1016/j.focus.2025.100409 | pmid=41078994 |pmc=12508837 }}</ref><ref>{{cite journal |vauthors=Rogers MA, Basu T, Kim C |title=Lower Incidence Rate of Type 1 Diabetes after Receipt of the Rotavirus Vaccine in the United States, 2001-2017 |journal=Scientific Reports |date=2019 |volume=9 |issue=1 |article-number=7727 |doi=10.1038/s41598-019-44193-4 | pmid=31197227 |pmc=6565744 |bibcode=2019NatSR...9.7727R }}</ref>
Combination immunotherapies are being explored to achieve more durable immune protection by using multiple agents together. For example, anti-CD3 antibodies may be combined with other immunomodulatory agents such as IL-1 blockers or checkpoint inhibitors.<ref>{{cite journal |title=Combination Immunotherapy for Type 1 Diabetes |date=2017 |journal=Current Diabetes Reports |volume=17 |issue=7 |article-number=50 |vauthors=Bone RN, Evans-Molina C |pmid=28534310 |doi=10.1007/s11892-017-0878-z |pmc=5774222}}</ref>
Finally, researchers are studying how environmental factors such as infections, diet, and stress may affect immune regulation through epigenetic modifications. The hope is that targeting these epigenetic changes could delay or prevent the onset of type 1 diabetes in high-risk individuals.<ref>{{cite journal |title=The Role of Epigenetics in Type 1 Diabetes |date=2017 |journal=Current Diabetes Reports |volume=17 |issue=10 |article-number=89 |vauthors=Jerram ST, Dang MN, Leslie RD |pmid=28815391 |doi=10.1007/s11892-017-0916-x |pmc=5559569}}</ref>
==Epidemiology== Type 1 diabetes makes up an estimated 10–15% of all diabetes cases{{sfn|Katsarou|Gudbjörnsdottir|Rawshani|Dabelea|2017|loc="Epidemiology"}} or 9 million cases worldwide.<ref name="WHO11">{{cite web |date=14 November 2024 |title=Diabetes |url=https://www.who.int/news-room/fact-sheets/detail/diabetes |url-status=live |archive-url=https://web.archive.org/web/20241115092255/https://www.who.int/news-room/fact-sheets/detail/diabetes |archive-date=15 November 2024 |access-date=28 August 2025 |work=World Health Organization |at=Type 1 diabetes |quote=In 2017 there were 9 million people with type 1 diabetes; the majority of them live in high-income countries.}}</ref><ref>{{Cite magazine |last=Rosen |first=Meghan |date=September 2025 |title=Hope for a diabetes treatment without insulin injections |url=<!-- accessed paper copy --> |department=News: Health & Medicine |magazine=Science News |page=12 |volume=207 |issue=9 |quote=Type 1 diabetes affects over 8 million people worldwide.}}</ref> 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.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Diagnosis"}}{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc=Table 36.1}} In contrast to most autoimmune diseases, type 1 diabetes is slightly more common in males than in females.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Diagnosis"}}
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.<ref name=Epi07>{{cite journal |vauthors=Aanstoot HJ, Anderson BJ, Daneman D, Danne T, Donaghue K, Kaufman F, Réa RR, Uchigata Y |title=The global burden of youth diabetes: perspectives and potential |journal=Pediatric Diabetes |volume=8 |issue=s8 |pages=1–44 |date=October 2007 |series=8 |pmid=17767619 |doi=10.1111/j.1399-5448.2007.00326.x |doi-access=free |s2cid=222102948}}</ref>{{sfn|Katsarou|Gudbjörnsdottir|Rawshani|Dabelea|2017|loc="Epidemiology"}}
Rates vary widely by country and region. The 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.{{sfn|Norris|Johnson|Stene|2020|loc="Trends in epidemiology"}}
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.<ref name=":0">{{cite web |title=Fast Facts |website=American Diabetes Association |url=http://professional.diabetes.org/admin/UserFiles/0%20-%20Sean/Documents/Fast_Facts_3-2015.pdf |archive-url=https://web.archive.org/web/20150429125655/http://professional.diabetes.org/admin/UserFiles/0%20-%20Sean/Documents/Fast_Facts_3-2015.pdf |archive-date=29 April 2015}}</ref>
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.<ref>{{cite web |title=Incidence of type 1 diabetes in Australia 2000–2013 |last=Australian Institute of Health and Welfare |date=2015 |url=https://www.aihw.gov.au/reports/diabetes/incidence-type-1-diabetes-australia-2000-2013/summary |access-date=13 February 2025 |url-status=live |archive-url=https://web.archive.org/web/20161007000927/http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=60129550898 |archive-date=7 October 2016}}</ref><ref>{{cite web |vauthors=Shaw J |title=diabetes: the silent pandemic and its impact on Australia |date=2012 |url=https://static.diabetesaustralia.com.au/s/fileassets/diabetes-australia/e7282521-472b-4313-b18e-be84c3d5d907.pdf |access-date=19 October 2016 |url-status=live |archive-url=https://web.archive.org/web/20161007001154/https://static.diabetesaustralia.com.au/s/fileassets/diabetes-australia/e7282521-472b-4313-b18e-be84c3d5d907.pdf |archive-date=7 October 2016}}</ref>
Since the 1950s, the incidence of type 1 diabetes has been gradually increasing across the world by an average 3–4% per year.{{sfn|Norris|Johnson|Stene|2020|loc="Trends in epidemiology"}} The increase is more pronounced in countries that began with a lower incidence of type 1 diabetes.{{sfn|Norris|Johnson|Stene|2020|loc="Trends in epidemiology"}}
==Type 1 diabetes in youth== Type 1 diabetes, also known as "juvenile-onset" diabetes is increasing in children and adolescents under the age of 15.<ref name=":9">{{cite journal |last1=Petschnig |first1=Renate |last2=Wagner |first2=Thomas |last3=Robubi |first3=Armin |last4=Baron |first4=Ramon |title=Effect of Strength Training on Glycemic Control and Adiponectin in Diabetic Children |date=October 2020 |journal=Medicine & Science in Sports & Exercise |language=en-US |volume=52 |issue=10 |pages=2172–2178 |issn=0195-9131 |pmid=32301853 |doi=10.1249/MSS.0000000000002356 |url=https://journals.lww.com/acsm-msse/fulltext/2020/10000/effect_of_strength_training_on_glycemic_control.13.aspx|url-access=subscription }}</ref> Type 1 diabetes is an autoimmune disease where the body attacks the beta-cells produced by the pancreas; therefore, causing the body to have insulin deficiency.<ref name=":10">{{cite journal |last1=García-Hermoso |first1=Antonio |last2=Ezzatvar |first2=Yasmin |last3=Huerta-Uribe |first3=Nidia |last4=Alonso-Martínez |first4=Alicia M. |last5=Chueca-Guindulain |first5=Maria J. |last6=Berrade-Zubiri |first6=Sara |last7=Izquierdo |first7=Mikel |last8=Ramírez-Vélez |first8=Robinson |title=Effects of exercise training on glycaemic control in youths with type 1 diabetes: A systematic review and meta-analysis of randomised controlled trials |date=June 2023 |journal=European Journal of Sport Science |language=en |volume=23 |issue=6 |pages=1056–1067 |issn=1746-1391 |pmid=35659492 |doi=10.1080/17461391.2022.2086489 |hdl=2454/43706 |hdl-access=free |url=https://onlinelibrary.wiley.com/doi/10.1080/17461391.2022.2086489}}</ref> The number of diagnoses is increasing all around the world.<ref name=":10"/>
===Management with exercise=== Children with type 1 diabetes typically manage their blood sugar levels with regular insulin injections; however, exercise can also play a vital role in the management of type 1 diabetes.<ref name=":9"/> For youth with type 1 diabetes, exercise is correlated with greater blood sugar control.<ref name=":10"/> HbA1c levels are reduced significantly when children with type 1 diabetes participate in structured exercise interventions.<ref name=":10"/> In one study, Garcia-Hermoso and colleagues found that high-intensity exercise, concurrent training, exercise intervention lasting 24 weeks or more, and exercise sessions lasting 60 minutes or more caused greater HbA1c reduction in children with type 1 diabetes.<ref name=":10"/> Garcia-Hermoso and colleagues also observed that exercise sessions lasting 60 minutes or more, high-intensity exercise, and concurrent training interventions led to a decrease in insulin dosage per day.<ref name=":10"/> Additionally, Petschnig and colleagues looked at the effect of strength training on blood sugar levels and they found that children with type 1 diabetes who performed strength training exercises for 17 weeks did not experience any change in HbA1c levels, but after 32 weeks of training experienced a significant decrease in HbA1c levels.<ref name=":9"/> Petschnig and colleagues also observed blood sugar levels decrease significantly following strength training sessions.<ref name=":9"/> Finally, the Diabetes Research in Children Network Study Group found that children who participated in prolonged aerobic exercise after school experienced a decrease in plasma glucose levels 40% below their baseline values.<ref name=":11">{{cite journal |last=The Diabetes Research in Children Network (DirecNet) Study Group |title=The Effects of Aerobic Exercise on Glucose and Counterregulatory Hormone Concentrations in Children With Type 1 Diabetes |date=2006-01-01 |journal=Diabetes Care |language=en |volume=29 |issue=1 |pages=20–25 |issn=0149-5992 |pmid=16373890 |doi=10.2337/diacare.29.1.20 |pmc=2396943}}</ref> 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.<ref name=":11"/> The Diabetes Research Group also found that after participating in prolonged aerobic exercise, 83% of participants had at least a 25% decrease in blood sugar levels.<ref name=":11"/> High-intensity and concurrent training interventions,<ref name=":10"/> strength training,<ref name=":9"/> and prolonged aerobic exercise<ref name=":11"/> all have been shown to help reduce HbA1c and blood glucose levels in children with type 1 diabetes; therefore, demonstrating that exercise plays a vital role in the management of type 1 diabetes.<ref name=":9"/>
==History== {{Main|History of diabetes}}
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.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Introduction"}} The connection between this inflammation and diabetes onset was further developed through the 1920s by Shields Warren,<!--source is vague. Reminder to look further into this--> and the term "insulitis" was coined by Hanns von Meyenburg in 1940 to describe the phenomenon.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Introduction"}}
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.<ref>{{cite journal |vauthors=Bottazzo GF, Florin-Christensen A, Doniach D |title=Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies |journal=Lancet |volume=2 |issue=7892 |pages=1279–1283 |date=November 1974 |pmid=4139522 |doi=10.1016/s0140-6736(74)90140-8}}</ref> 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.<ref>{{cite journal |vauthors=Herold KC, Vignali DA, Cooke A, Bluestone JA |title=Type 1 diabetes: translating mechanistic observations into effective clinical outcomes |journal=Nature Reviews. Immunology |volume=13 |issue=4 |pages=243–256 |date=April 2013 |pmid=23524461 |doi=10.1038/nri3422 |pmc=4172461}}</ref> The name ''juvenile diabetes'' was used earlier as it is often first diagnosed in childhood.
==Society and culture== {{See also|List of people with type 1 diabetes}}
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.<ref>{{cite news |vauthors=Johnson L |title=Study: Cost of diabetes $218B |agency=Associated Press |work=USA Today |date=18 November 2008 |url=https://www.usatoday.com/news/health/2008-11-18-diabetes-cost_N.htm |archive-url=https://web.archive.org/web/20120701180245/http://www.usatoday.com/news/health/2008-11-18-diabetes-cost_N.htm |archive-date=1 July 2012}}</ref> 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 is spent on individuals with type 1 and 2 diabetes.<ref name=":0"/>
==Research== {{Further|Diabetes management#Research}} Funding for research into type 1 diabetes originates from the 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.<ref>{{cite web |title=About JDRF |website=JDRF |url=https://www.jdrf.org/about/ |access-date=24 March 2024}}</ref> Other charities include the American Diabetes Association, Diabetes UK, Diabetes Research and Wellness Foundation,<ref>{{cite web |title=About DRWF |website=Diabetes Research & Wellness Foundation |url=https://www.diabeteswellness.net/ |url-status=live |archive-url=https://web.archive.org/web/20130511223632/http://www.diabeteswellness.net/ |archive-date=11 May 2013}}</ref> Diabetes Australia, and the Canadian Diabetes Association.
===Artificial pancreas=== 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.{{sfn|Boughton|Hovorka|2020|loc="Introduction"}} 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.{{sfn|Boughton|Hovorka|2020|loc="Regulatory Approval of Closed-Loop Systems"}} 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.<ref>{{cite journal |vauthors=Ramli R, Reddy M, Oliver N |title=Artificial Pancreas: Current Progress and Future Outlook in the Treatment of Type 1 Diabetes |journal=Drugs |volume=79 |issue=10 |pages=1089–1101 |date=July 2019 |pmid=31190305 |doi=10.1007/s40265-019-01149-2 |hdl=10044/1/71348 |hdl-access=free |s2cid=186207231}}</ref>
===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.<ref name=":1">{{cite book |title=Animal models of diabetes: methods and protocols |publisher=Humana Press |date=2020 |vauthors=King AJ |isbn=978-1-0716-0385-7 |location=New York, NY |oclc=1149391907}}{{page needed|date=October 2022}}</ref>
The nonobese diabetic (NOD) mouse is the most widely studied model of type 1 diabetes.<ref name=":1"/> It is an inbred strain that spontaneously develops type 1 diabetes in 30–100% of female mice depending on housing conditions.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Animal models"}} Diabetes in NOD mice is caused by several genes, primarily MHC genes involved in antigen presentation.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Animal models"}} Like diabetic humans, NOD mice develop islet autoantibodies and inflammation in the islet, followed by reduced insulin production and hyperglycemia.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Animal models"}}<ref>{{cite web |title=NOD/ShiLtJ |publisher=The Jackson Laborataory |url=https://www.jax.org/strain/001976 |access-date=18 January 2022}}</ref> 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.{{sfn|Atkinson|Mcgill|Dassau|Laffel|2020|loc="Animal models"}} 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.<ref name=":2">{{cite journal |vauthors=Pandey S, Dvorakova MC |title=Future Perspective of Diabetic Animal Models |journal=Endocrine, Metabolic & Immune Disorders Drug Targets |volume=20 |issue=1 |pages=25–38 |date=2020-01-07 |pmid=31241444 |doi=10.2174/1871530319666190626143832 |pmc=7360914}}</ref> In addition to sex, breeding conditions, gut microbiome composition or diet also influence the onset of T1D.<ref>{{cite book |vauthors=Chen D, Thayer TC, Wen L, Wong FS |title=Animal Models of Diabetes |chapter=Mouse Models of Autoimmune Diabetes: The Nonobese Diabetic (NOD) Mouse |series=Methods in Molecular Biology |volume=2128 |pages=87–92 |date=2020 |publisher=Springer US |isbn=978-1-0716-0384-0 |veditors=King AJ |place=New York, NY |pmid=32180187 |doi=10.1007/978-1-0716-0385-7_6 |pmc=8253669}}</ref>
The BioBreeding Diabetes-Prone (BB) rat is another widely used spontaneous experimental model for T1D. The onset of diabetes occurs, in up to 90% of individuals (regardless of sex) at 8–16 weeks of age.<ref name=":2"/> During insulitis, the pancreatic islets are infiltrated by T lymphocytes, B lymphocytes, macrophages, and NK cells, with the difference from the human course of insulitis being that CD4 + T lymphocytes are markedly reduced and CD8 + T lymphocytes are almost absent. The aforementioned lymphopenia is the major drawback of this model. The disease is characterized by hyperglycemia, hypoinsulinemia, weight loss, ketonuria, and the need for insulin therapy for survival.<ref name=":2"/> BB Rats are used to study the genetic aspects of T1D and are also used for interventional studies and diabetic nephropathy studies.<ref>{{cite book |vauthors=Lenzen S, Arndt T, Elsner M, Wedekind D, Jörns A |title=Animal Models of Diabetes |chapter=Rat Models of Human Type 1 Diabetes |series=Methods in Molecular Biology |volume=2128 |pages=69–85 |date=2020 |publisher=Springer US |isbn=978-1-0716-0384-0 |place=New York, NY |veditors=King AJ |pmid=32180186 |doi=10.1007/978-1-0716-0385-7_5 |s2cid=212741496}}</ref>
LEW-1AR1 / -iddm rats are derived from congenital Lewis rats and represent a rarer spontaneous model for T1D. These rats develop diabetes at about 8–9 weeks of age with no sex differences, unlike NOD mice.<ref>{{cite journal |vauthors=Al-Awar A, Kupai K, Veszelka M, Szűcs G, Attieh Z, Murlasits Z, Török S, Pósa A, Varga C |title=Experimental Diabetes Mellitus in Different Animal Models |journal=Journal of Diabetes Research |volume=2016 |article-number=9051426 |date=2016 |pmid=27595114 |doi=10.1155/2016/9051426 |doi-access=free |pmc=4993915}}</ref> In LEW mice, diabetes presents with hyperglycemia, glycosuria, ketonuria, and polyuria.<ref>{{cite journal |vauthors=Lenzen S, Tiedge M, Elsner M, Lortz S, Weiss H, Jörns A, Klöppel G, Wedekind D, Prokop CM, Hedrich HJ |title=The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes mellitus |journal=Diabetologia |volume=44 |issue=9 |pages=1189–1196 |date=September 2001 |pmid=11596676 |doi=10.1007/s001250100625 |doi-access=free}}</ref><ref name=":2"/> 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. This model is suitable for intervention studies or for the search for predictive biomarkers. It is also possible to observe individual phases of pancreatic infiltration by immune cells. The advantage of congenic LEW mice is also the good viability after the manifestation of T1D (compared to NOD mice and BB rats).<ref name=":3">{{cite journal |vauthors=Lenzen S |title=Animal models of human type 1 diabetes for evaluating combination therapies and successful translation to the patient with type 1 diabetes |journal=Diabetes/Metabolism Research and Reviews |volume=33 |issue=7 |article-number=e2915 |date=October 2017 |pmid=28692149 |doi=10.1002/dmrr.2915 |s2cid=34331597}}</ref>
====Chemically induced==== The chemical compounds aloxan and streptozotocin (STZ) are commonly used to induce diabetes and destroy β-cells in mouse/rat animal models.<ref name=":2"/> In both cases, it is a cytotoxic analog of glucose that passes through GLUT2 transport and accumulates in β-cells, causing their destruction. The chemically induced destruction of β-cells leads to decreased insulin production, hyperglycemia, and weight loss in the experimental animal.<ref>{{cite journal |vauthors=Radenković M, Stojanović M, Prostran M |title=Experimental diabetes induced by alloxan and streptozotocin: The current state of the art |journal=Journal of Pharmacological and Toxicological Methods |volume=78 |pages=13–31 |date=March 2016 |pmid=26596652 |doi=10.1016/j.vascn.2015.11.004}}</ref> The animal models prepared in this way are suitable for research into blood sugar-lowering drugs and therapies (e.g., for testing new insulin preparations). They are also the most commonly used genetically induced T1D model is the so-called AKITA mouse (originally C57BL/6NSIc mouse). 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. Decreased insulin production is then associated with hyperglycemia, polydipsia, and polyuria. If severe diabetes develops within 3–4 weeks, AKITA mice survive no longer than 12 weeks without treatment intervention. The description of the etiology of the disease shows that, unlike spontaneous models, the early stages of the disease are not accompanied by insulitis.<ref>{{cite book |vauthors=Salpea P, Cosentino C, Igoillo-Esteve M |title=Animal Models of Diabetes |chapter=A Review of Mouse Models of Monogenic Diabetes and ER Stress Signaling |series=Methods in Molecular Biology |volume=2128 |pages=55–67 |date=2020 |publisher=Springer US |isbn=978-1-0716-0384-0 |place=New York, NY |veditors=King AJ |pmid=32180185 |doi=10.1007/978-1-0716-0385-7_4 |hdl=2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/326378 |s2cid=212740474}}</ref> AKITA mice are used to test drugs targeting endoplasmic reticulum stress reduction, to test islet transplants, and to study diabetes-related complications such as nephropathy, sympathetic autonomic neuropathy, and vascular disease.<ref name=":2"/><ref>{{cite book |vauthors=Chang JH, Gurley SB |chapter=Assessment of Diabetic Nephropathy in the Akita Mouse |title=Animal Models in Diabetes Research |series=Methods in Molecular Biology |volume=933 |pages=17–29 |date=2012 |publisher=Humana Press |isbn=978-1-62703-067-0 |veditors=Hans-Georg J, Hadi AH, Schürmann A |place=Totowa, NJ |pmid=22893398 |doi=10.1007/978-1-62703-068-7_2}}</ref> for testing transplantation therapies. Their advantage is mainly the low cost; the disadvantage is the cytotoxicity of the chemical compounds.<ref>{{cite book |vauthors=King AJ, Estil Les E, Montanya E |title=Animal Models of Diabetes |chapter=Use of Streptozotocin in Rodent Models of Islet Transplantation |series=Methods in Molecular Biology |volume=2128 |pages=135–147 |date=2020 |publisher=Springer US |isbn=978-1-0716-0384-0 |place=New York, NY |veditors=King AJ |pmid=32180191 |doi=10.1007/978-1-0716-0385-7_10 |s2cid=212739708}}</ref>
====Genetically induced==== Type 1 diabetes (T1D) is a multifactorial autoimmune disease with a strong genetic component. 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.
The most significant genetic contribution to T1D comes from the human leukocyte antigen (HLA) region on chromosome 6p21.<ref>{{cite journal |last1=Sia |first1=Charles |last2=Weinem |first2=Michael |title=The role of HLA class I gene variation in autoimmune diabetes |date=2005 |journal=The Review of Diabetic Studies |volume=2 |issue=2 |pages=97–109 |issn=1614-0575 |pmid=17491685 |doi=10.1900/RDS.2005.2.97 |doi-broken-date=12 July 2025 |pmc=1783552}}</ref> The HLA class II genes, particularly '''HLA-DR''' and '''HLA-DQ''', are the strongest genetic determinants of T1D risk. Specific combinations of alleles such as '''HLA-DR3-DQ2''' and '''HLA-DR4-DQ8''' have been associated with a higher risk of developing T1D.<ref name="Todd 457–467">{{cite journal |last=Todd |first=John A. |title=Etiology of type 1 diabetes |date=2010-04-23 |journal=Immunity |volume=32 |issue=4 |pages=457–467 |issn=1097-4180 |pmid=20412756 |doi=10.1016/j.immuni.2010.04.001 |doi-access=free }}</ref> Individuals carrying both of these haplotypes (heterozygous DR3/DR4) are at an even greater risk. 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.<ref>{{cite journal |last=Roep |first=Bart O. |title=The role of T-cells in the pathogenesis of Type 1 diabetes: from cause to cure |date=March 2003 |journal=Diabetologia |volume=46 |issue=3 |pages=305–321 |issn=0012-186X |pmid=12687328 |doi=10.1007/s00125-003-1089-5 }}</ref>
Conversely, some HLA haplotypes, such as '''HLA-DR15-DQ6''', are associated with protection against T1D, suggesting that variations in these immune-related genes can either predispose or protect against the disease.<ref>{{cite journal |last1=Noble |first1=Janelle A. |last2=Erlich |first2=Henry A. |title=Genetics of type 1 diabetes |date=January 2012 |journal=Cold Spring Harbor Perspectives in Medicine |volume=2 |issue=1 |article-number=a007732 |issn=2157-1422 |pmid=22315720 |doi=10.1101/cshperspect.a007732 |pmc=3253030}}</ref>
In addition to HLA, multiple non-HLA genes have been implicated in T1D susceptibility. Genome-wide association studies (GWAS) have identified over 50 loci associated with an increased risk of T1D.<ref>{{cite journal |last1=Grant |first1=Struan F. A. |last2=Hakonarson |first2=Hakon |title=Genome-wide association studies in type 1 diabetes |date=April 2009 |journal=Current Diabetes Reports |volume=9 |issue=2 |pages=157–163 |issn=1539-0829 |pmid=19323961 |doi=10.1007/s11892-009-0026-5 }}</ref> Some of the most notable genes include:
* '''INS''': The insulin gene (INS) on chromosome 11p15 is one of the earliest identified non-HLA genes linked to T1D. A variable number tandem repeat (VNTR) polymorphism in the promoter region of the insulin gene affects its thymic expression, with certain alleles reducing the ability to develop immune tolerance to insulin, a key autoantigen in T1D.<ref>{{cite journal |title=Genetics of Type 1 Diabetes |date=2011 |journal=Clinical Chemistry |volume=57 |issue=2 |pages=176–185 |vauthors=Steck AK, Rewers MJ |pmid=21205883 |doi=10.1373/clinchem.2010.148221 |pmc=4874193}}</ref> * '''PTPN22''': This gene encodes a protein tyrosine phosphatase involved in T-cell receptor signaling. A common single-nucleotide polymorphism (SNP), '''R620W''', in the PTPN22 gene is associated with an increased risk of T1D and other autoimmune diseases, suggesting its role in modulating immune responses.<ref>{{cite journal |last1=Vang |first1=Torkel |last2=Miletic |first2=Ana V. |last3=Bottini |first3=Nunzio |last4=Mustelin |first4=Tomas |title=Protein tyrosine phosphatase PTPN22 in human autoimmunity |date=September 2007 |journal=Autoimmunity |volume=40 |issue=6 |pages=453–461 |issn=0891-6934 |pmid=17729039 |doi=10.1080/08916930701464897 }}</ref> * '''IL2RA''': The interleukin-2 receptor alpha (IL2RA) gene, located on chromosome 10p15, plays a crucial role in regulating immune tolerance and T-cell activation. Variants in IL2RA affect the susceptibility to T1D by altering the function of regulatory T-cells, which help maintain immune homeostasis.<ref>{{cite journal |last1=Garg |first1=Garima |last2=Tyler |first2=Jennifer R. |last3=Yang |first3=Jennie H. M. |last4=Cutler |first4=Antony J. |last5=Downes |first5=Kate |last6=Pekalski |first6=Marcin |last7=Bell |first7=Gwynneth L. |last8=Nutland |first8=Sarah |last9=Peakman |first9=Mark |last10=Todd |first10=John A. |last11=Wicker |first11=Linda S. |last12=Tree |first12=Timothy I. M. |title=Type 1 diabetes-associated IL2RA variation lowers IL-2 signaling and contributes to diminished CD4+CD25+ regulatory T cell function |date=2012-05-01 |journal=Journal of Immunology |volume=188 |issue=9 |pages=4644–4653 |issn=1550-6606 |pmid=22461703 |doi=10.4049/jimmunol.1100272 |pmc=3378653}}</ref> * '''CTLA4''': The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene is another immune-related gene associated with T1D. CTLA4 acts as a negative regulator of T-cell activation, and certain variants are linked to impaired immune regulation and a higher risk of autoimmunity.
T1D is considered a polygenic disease, meaning that multiple genes contribute to its development. 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.<ref>{{citation |last1=Dean |first1=Laura |title=Genetic Factors in Type 1 Diabetes |date=2004-07-07 |work=The Genetic Landscape of Diabetes [Internet] |publisher=National Center for Biotechnology Information (US) |language=en |last2=McEntyre |first2=Jo |url=https://www.ncbi.nlm.nih.gov/books/NBK1662/ |access-date=2024-10-20}}</ref> Family studies show that T1D has a relatively high heritability, with siblings of affected individuals having about a 6–10% risk of developing the disease, compared to a 0.3% risk in the general population.<ref>{{cite journal |last1=Leslie |first1=R. David |last2=Evans-Molina |first2=Carmella |last3=Freund-Brown |first3=Jacquelyn |last4=Buzzetti |first4=Raffaella |last5=Dabelea |first5=Dana |last6=Gillespie |first6=Kathleen M. |last7=Goland |first7=Robin |last8=Jones |first8=Angus G. |last9=Kacher |first9=Mark |last10=Phillips |first10=Lawrence S. |last11=Rolandsson |first11=Olov |last12=Wardian |first12=Jana L. |last13=Dunne |first13=Jessica L. |title=Adult-Onset Type 1 Diabetes: Current Understanding and Challenges |date=November 2021 |journal=Diabetes Care |volume=44 |issue=11 |pages=2449–2456 |issn=1935-5548 |pmid=34670785 |doi=10.2337/dc21-0770 |pmc=8546280}}</ref>
The risk of T1D is also influenced by the presence of affected first-degree relatives. For instance, children of fathers with T1D have a higher risk of developing the disease compared to children of mothers with T1D. Monozygotic (identical) twins have a concordance rate of about 30–50%, highlighting the importance of both genetic and environmental factors in disease onset.<ref name="Todd 457–467"/>
Recent research has also focused on the role of epigenetics and gene-environment interactions in T1D development.<ref>{{cite book |last1=Xie |first1=Zhiguo |last2=Chang |first2=Christopher |last3=Huang |first3=Gan |last4=Zhou |first4=Zhiguang |title=Epigenetics in Allergy and Autoimmunity |date=2020 |chapter=The Role of Epigenetics in Type 1 Diabetes |chapter-url=https://pubmed.ncbi.nlm.nih.gov/32445098/ |series=Advances in Experimental Medicine and Biology |volume=1253 |pages=223–257 |issn=0065-2598 |isbn=978-981-15-3448-5 |pmid=32445098 |doi=10.1007/978-981-15-3449-2_9}}</ref> Environmental factors such as viral infections, early childhood diet, and gut microbiome composition are thought to trigger the autoimmune process in genetically susceptible individuals.<ref>{{cite journal |title=Environmental Factors Associated With Type 1 Diabetes |date=2019 |journal=Frontiers in Endocrinology |volume=10 |article-number=592 |vauthors=Esposito S, Toni G, Tascini G, Santi E, Berioli MG, Principi N |pmid=31555211 |doi=10.3389/fendo.2019.00592 |doi-access=free |pmc=6722188}}</ref> Epigenetic modifications, such as DNA methylation and histone modifications, may influence gene expression in response to these environmental triggers, further modulating the risk of developing T1D.
While much progress has been made in understanding the genetic basis of T1D, ongoing research aims to unravel the complex interplay between genetic susceptibility, immune regulation, and environmental influences that contribute to disease pathogenesis.<ref>{{cite journal |last1=Mittal |first1=Rahul |last2=Camick |first2=Nathanael |last3=Lemos |first3=Joana R. N. |last4=Hirani |first4=Khemraj |title=Gene-environment interaction in the pathophysiology of type 1 diabetes |date=2024-01-26 |journal=Frontiers in Endocrinology |language=English |volume=15 |article-number=1335435 |issn=1664-2392 |pmid=38344660 |doi=10.3389/fendo.2024.1335435 |doi-access=free |pmc=10858453}}</ref>
====Virally induced==== Viral infections play a role in the development of several autoimmune diseases, including type 1 diabetes. However, the mechanisms by which viruses are involved in the induction of type 1 DM are not fully understood. Virus-induced models are used to study the etiology and pathogenesis of the disease, in particular the mechanisms by which environmental factors contribute to or protect against the occurrence of type 1 DM.<ref>{{cite book |vauthors=Christoffersson G, Flodström-Tullberg M |title=Animal Models of Diabetes |chapter=Mouse Models of Virus-Induced Type 1 Diabetes |volume=2128 |pages=93–105 |date=2020 |publisher=Springer US |isbn=978-1-0716-0384-0 |series=Methods in Molecular Biology |place=New York, NY |veditors=King AJ |pmid=32180188 |doi=10.1007/978-1-0716-0385-7_7 |s2cid=212739248}}</ref> Among the most commonly used are coxsackievirus, lymphocytic choriomeningitis virus, encephalomyocarditis virus, and Kilham rat virus. Examples of virus-induced animals include NOD mice infected with coxsackie B4 that developed type 1 DM within two weeks.<ref>{{cite journal |vauthors=King AJ |title=The use of animal models in diabetes research |journal=British Journal of Pharmacology |volume=166 |issue=3 |pages=877–894 |date=June 2012 |pmid=22352879 |doi=10.1111/j.1476-5381.2012.01911.x |pmc=3417415}}</ref>
==References== {{Reflist}}
==Works cited== {{Refbegin|30em}} * {{cite journal |author=American Diabetes Association |title=6. Glycemic Targets: ''Standards of Medical Care in Diabetes-2021'' |journal=Diabetes Care |volume=44 |issue=Suppl 1 |pages=S73–S84 |date=January 2021 |pmid=33298417 |doi=10.2337/dc21-S006 |doi-access=free |s2cid=228087604 |ref={{harvid|American Diabetes Association (6)|2021}}}} * {{cite book |vauthors=Atkinson MA, Mcgill DE, Dassau E, Laffel L |chapter=Type 1 diabetes mellitus |title=Williams Textbook of Endocrinology |publisher=Elsevier |date=2020 |pages=1403–1437}} * {{cite journal |vauthors=Boughton CK, Hovorka R |title=The artificial pancreas |journal=Curr Opin Organ Transplant |volume=25 |issue=4 |pages=336–342 |date=August 2020 |pmid=32618719 |doi=10.1097/MOT.0000000000000786 |s2cid=220326946}} * {{cite book |vauthors=Brownlee M, Aiello LP, Sun JK, Cooper ME, Feldman EL, Plutzky J, Boulton AJ |chapter=Complications of Diabetes Mellitus |title=Williams Textbook of Endocrinology |publisher=Elsevier |date=2020 |pages=1438–1524 |isbn=978-0-323-55596-8}} * {{cite journal |vauthors=Butler AE, Misselbrook D |title=Distinguishing between type 1 and type 2 diabetes |journal=The BMJ |volume=370 |article-number=m2998 |date=August 2020 |pmid=32784223 |doi=10.1136/bmj.m2998 |s2cid=221097632}} * {{cite journal |vauthors=Cashen K, Petersen T |title=Diabetic Ketoacidosis |journal=Pediatr Rev |volume=40 |issue=8 |pages=412–420 |date=August 2019 |pmid=31371634 |doi=10.1542/pir.2018-0231 |s2cid=199381655}} * {{cite journal |vauthors=Dayan CM, Korah M, Tatovic D, Bundy BN, Herold KC |title=Changing the landscape for type 1 diabetes: the first step to prevention |journal=Lancet |volume=394 |issue=10205 |pages=1286–1296 |date=October 2019 |pmid=31533907 |doi=10.1016/S0140-6736(19)32127-0 |s2cid=202575545}} * {{cite journal |vauthors=Dean PG, Kukla A, Stegall MD, Kudva YC |title=Pancreas transplantation |journal=The BMJ |volume=357 |article-number=j1321 |date=April 2017 |pmid=28373161 |doi=10.1136/bmj.j1321 |s2cid=11374615}} * {{cite book |vauthors=Delli AJ, Lernmark A |chapter=Type 1 (insulin-dependent) diabetes mellitus: etiology, pathogenesis, prediction, and prevention |title=Endocrinology: Adult and Pediatric |pages=672–690 |edition=7 |publisher=Saunders |date=2016 |veditors=Jameson JL |isbn=978-0-323-18907-1}} * {{cite journal |vauthors=DiMeglio LA, Evans-Molina C, Oram RA |title=Type 1 diabetes |journal=Lancet |volume=391 |issue=10138 |pages=2449–2462 |date=June 2018 |pmid=29916386 |doi=10.1016/S0140-6736(18)31320-5 |pmc=6661119}} * {{cite journal |vauthors=Katsarou A, Gudbjörnsdottir S, Rawshani A, Dabelea D, Bonifacio E, Anderson BJ, Jacobsen LM, Schatz DA, Lernmark Å |title=Type 1 diabetes mellitus |journal=Nature Reviews. Disease Primers |volume=3 |article-number=17016 |date=March 2017 |pmid=28358037 |doi=10.1038/nrdp.2017.16 |s2cid=23127616}} * {{cite journal |vauthors=Norris JM, Johnson RK, Stene LC |title=Type 1 diabetes-early life origins and changing epidemiology |journal=The Lancet. Diabetes & Endocrinology |volume=8 |issue=3 |pages=226–238 |date=March 2020 |pmid=31999944 |doi=10.1016/S2213-8587(19)30412-7 |pmc=7332108}} * {{cite journal |vauthors=Redondo MJ, Steck AK, Pugliese A |title=Genetics of type 1 diabetes |journal=Pediatric Diabetes |volume=19 |issue=3 |pages=346–353 |date=May 2018 |pmid=29094512 |doi=10.1111/pedi.12597 |pmc=5918237}} * {{cite journal |vauthors=Repaske DR |title=Medication-induced diabetes mellitus |journal=Pediatr Diabetes |volume=17 |issue=6 |pages=392–7 |date=September 2016 |pmid=27492964 |doi=10.1111/pedi.12406 |doi-access=free |s2cid=4684512}} * {{cite journal |vauthors=Rickels MR, Robertson RP |title=Pancreatic Islet Transplantation in Humans: Recent Progress and Future Directions |journal=Endocr Rev |volume=40 |issue=2 |pages=631–668 |date=April 2019 |pmid=30541144 |doi=10.1210/er.2018-00154 |pmc=6424003}} * {{cite journal |vauthors=Shapiro AM, Pokrywczynska M, Ricordi C |title=Clinical pancreatic islet transplantation |journal=Nat Rev Endocrinol |volume=13 |issue=5 |pages=268–277 |date=May 2017 |pmid=27834384 |doi=10.1038/nrendo.2016.178 |s2cid=28784928}} * {{cite journal |vauthors=Smith A, Harris C |title=Type 1 diabetes: Management strategies |journal=American Family Physician |date=August 2018 |volume=98 |issue=3 |pages=154–156 |pmid=30215903 |url=https://www.aafp.org/afp/2018/0801/p154.html |access-date=12 January 2022}} * {{cite journal |vauthors=von Scholten BJ, Kreiner FF, Gough SC, von Herrath M |title=Current and future therapies for type 1 diabetes |journal=Diabetologia |volume=64 |issue=5 |pages=1037–1048 |date=May 2021 |pmid=33595677 |doi=10.1007/s00125-021-05398-3 |pmc=8012324}} * {{cite book |chapter=Management of Diabetes in Children |title=Endocrinology: Adult and Pediatric |year=2016 |last1=Wolsdorf |first1=Joseph I. |last2=Garvey |first2=Katharine C. |pages=854–882.e6 |isbn=978-0-323-18907-1 |doi=10.1016/B978-0-323-18907-1.00049-4}} {{Refend}}
==External links== * [https://www.niddk.nih.gov/about-niddk/strategic-plans-reports/diabetes-in-america-2nd-edition Diabetes in America, 2nd Edition] (textbook) (PDFs) {{Webarchive|url=https://web.archive.org/web/20110425052512/http://diabetes.niddk.nih.gov/dm/pubs/america/contents.htm |date=25 April 2011}} – National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) * [https://diabetesatlas.org/ IDF Diabetes Atlas] * [http://www.diabetes.org/type-1-diabetes.jsp Type 1 Diabetes] {{Webarchive|url=https://web.archive.org/web/20091030082136/https://www.diabetes.org/type-1-diabetes.jsp |date=30 October 2009}} at the American Diabetes Association * [https://diabetesjournals.org/care/issue/42/Supplement_1 ADA's Standards of Medical Care in Diabetes 2019]
{{Medical resources | DiseasesDB=3649 | ICD10={{ICD10|E|10||e|10}} | ICD9={{ICD9|250.01}} | OMIM=222100 | MedlinePlus=000305 | eMedicineSubj=med | eMedicineTopic=546 | MeshID=D003922 | Scholia=Q124407 }} {{Diabetes}} {{Disease of the pancreas and glucose metabolism}} {{Hypersensitivity disease by cause}}
{{DEFAULTSORT:Diabetes Mellitus Type 1}} Category:Autoimmune diseases Category:Types of diabetes