Immune checkpoint inhibitor-induced diabetes leading to distress and worsening quality of life: A case report

Immune checkpoint inhibitor-induced diabetes leading to distress and worsening quality of life: A case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Immune checkpoint inhibitor-induced diabetes leading to distress and worsening quality of life: A case report Stephanie Saey, Jas Sara, Pankaj Shah This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8149829/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract An 86-year-old woman with metastatic non-small cell lung carcinoma on Pembrolizumab presented to the Emergency Department with diabetic ketoacidosis; after appropriate treatment she was transitioned to basal/bolus insulin regimen. She had chosen to receive Immune Checkpoint Inhibitor (ICI) instead of radiotherapy, as she wished to preserve her quality of life. With the demands of management of ICI-induced irreversible insulin deficient diabetes she now has substantial worsening of quality of life with considerable anxiety and depressed mood. ICI-induced diabetes and DKA is more common in patients treated with Pembrolizumab than suggested by early trials. In addition to highlighting the importance of counseling patients on the signs and symptoms of hyperglycemia for earlier detection, our case calls for considering the psychological impact of managing a chronic illness in patient education prior to initiating ICI therapy. diabetic ketoacidosis diabetes immune checkpoint inhibitor immune related adverse events case report Introduction Immune checkpoint inhibitors (ICIs) have transformed cancer treatment over the last decade. Pembrolizumab is an ICI that inhibits Programmed cell death protein 1 (PD-1) on T cells, a receptor often upregulated in cancers to evade immune destruction. In binding to PD-1, Pembrolizumab releases the brakes on T-cell activation to restore immune function ( 1 ). This mechanism makes Pembrolizumab an effective antitumor agent but also predisposes individuals to many autoimmune complications. Termed immune-related adverse events (irAEs), these toxicities affect a variety of organs, manifesting as endocrinopathies, colitis, hepatitis, and nephritis, among others ( 2 ). Many irAEs are acute and self-limiting, but chronic sequelae are underreported, particularly their impact on quality of life. This gap in understanding is critical when guiding shared decision making, and when working with older individuals who may be more vulnerable. Here we highlight a case of an 86-year-old woman who developed significant distress upon being diagnosed with new-onset diabetes presenting as diabetic ketoacidosis (DKA) while undergoing Pembrolizumab therapy for non-small cell lung cancer (NSCLC). Case Presentation An 86-year-old white female presented to the Emergency Department (ED) with a six-day history of progressively worsening nausea, anorexia, weakness, “brain fog,” polydipsia, and polyuria. She denied abdominal pain, diarrhea, vomiting, flu-like illness, upper respiratory infection, or corticosteroid use. The patient had recently been diagnosed with Stage IV non-small cell lung adenocarcinoma, poorly differentiated (PD-L1 100%, KRAS G12V-positive). She had begun Pembrolizumab 2mg for palliative intent, receiving cycle #2 two weeks prior to presentation. Immunotherapy was chosen as she did not have a targetable alteration. She had declined radiation therapy, wishing to avoid side efects and “preserve [my] quality of life.” A widow of 18 years, the patient reported living alone but was active in the community and enjoyed meeting friends for lunch and being part of breakfast clubs. Despite having Stage IV cancer, she was quoted as feeling “great” at the time of her oncology appointments. Baseline endocrine workup was significant for prediabetes (A1c 5.9%) and subclinical hypothyroidism (TSH 5.8 mIU/L). Other blood tests were unremarkable. She had fibromyalgia, obesity (BMI 35 kg/m2), and well-controlled hypertension. Her only medication was Pembrolizumab. On arrival, she was afebrile and hemodynamically stable though slightly tachypneic (respiratory rate 22). Laboratory evaluation confirmed DKA: glucose of 24.48 mmol/L, venous blood gas pH 7.14, bicarbonate 14 mmol/L, anion gap 18, and beta hydroxybutyrate 6.2 mmol/L. Workup for secondary causes of DKA was negative. Pembrolizumab-induced DKA was diagnosed. She received intravenous insulin and fluids, improved, and was transitioned to multiple daily insulin injection (MDI) insulin therapy. Insulin deficiency was documented with undetectable C-peptide was < 0.1 when plasma glucose was 204. She established Endocrinology follow-up and continues to struggle with glycemic control. Current management includes continuous glucose monitoring and 4–5 daily injections. Each meal requires carbohydrate estimation, glucose review, and bolus dose calculation. She follows up every 2–3 months and contacts diabetes educators nearly every other week. Despite an excellent Positron Emission Tomography scan response, she declined further Pembrolizumab, describing being “scared to death” of additional cycles. The diabetes diagnosis caused profound psychological burden, which she described as “traumatic.” Her GAD-7 score worsened from 6 (mild anxiety) pre-treatment to 15 (severe anxiety). She has begun therapy to cope with her anxiety. Discussions and Conclusion Knowledge of irAEs is growing amidst the widespread use of ICIs ( 2 ). Early clinical trials and subsequent studies, including case reports, have focused on recognizing acute, life-threatening irAEs and physiological risk factors ( 3 , 4 , 5 ). While critical, this emphasis has overshadowed the broader spectrum of toxicities, especially those with chronic, long-term quality-of-life impact. As real-world data accumulates, recognition of chronic irAEs is increasing, but they remain underreported in clinical trials ( 6 , 7 , 8 ). The Table below summarizes the incidence of several acute irAEs reported in initial anti–PD-1 trials and contrasts them with a more recent retrospective study that documented both acute and chronic irAEs in patients receiving ICI therapy ( 3 , 4 , 5 , 7 ). While limited, existing data suggest chronic irAEs are associated with measurable declines in health-related quality of life ( 9 ). Our case uniquely illustrates the psychological burden of ICI-induced diabetes in an elderly patient. Diabetes increases risks of depression, anxiety, and burnout ( 10 , 11 ). In older adults, these are compounded by vulnerability to complications such as nephropathy, cardiovascular disease, and geriatric syndromes ( 12 ). In our patient, daily demands of insulin management and diet contributed to significant distress. The balance of survival benefit versus diminished quality of life becomes especially salient in the context of advanced cancer. Older adults are underrepresented in clinical trials, creating gaps in understanding chronic irAEs ( 2 , 9 , 14 ). Observational studies suggest irAEs may be especially debilitating in this group due to diminished reserve and comorbidities ( 12 , 14 ). Complex diabetes self-management can interfere with social interaction and exercise, both protective for cognition and mood ( 13 , 15 ). Future studies must prioritize geriatric representation and include patient-centered endpoints such as functional status and quality of life. Clinicians should consider early referral to mental health services and diabetes education as part of the standard management of ICI-induced diabetes, particularly in older adults. Collaborative care models that include behavioral health professionals, diabetes educators, and social workers may improve long-term outcomes and better support patients navigating the dual burden of cancer and chronic endocrine disease ( 16 ). Finally, this case underscores the importance of comprehensive pre-treatment counseling. While acute risks such as DKA are often discussed, the potential permanence and psychological toll of chronic irAEs may be overlooked ( 12 ). Counseling should address both physical and emotional demands, especially in older adults, to align treatment with patient values and goals ( 14 , 16 , 17 ). Conclusion Although limited by its single-patient focus, this case highlights a clinically significant and underrecognized issue: the long-term psychological and quality of life impact of chronic immune-related adverse events (irAEs) like ICI-induced diabetes in elderly patients. It reinforces the value of case reports in identifying vulnerable populations and informing future patient-centered research. As ICI use expands, particularly in palliative care settings, thorough patient counseling that addresses both physical and emotional burdens is essential to support informed decision-making. Future studies should prioritize geriatric populations and quality-of-life outcomes. Declarations HUMAN ETHICS The requirement of ethical approval for this study was waived by the Mayo Clinic Institutional Review Board and the protocol was conducted in accordance with the ethical standards as larid down in the 1964 Declaration of Helsinki and its later amendments. CONSENT TO PARTICIPATE Informed consent was obtained from the patient for participation in this study. CONSENT TO PUBLISH Written informed consent for publication was obtained from the patient. CLINICAL TRIAL NUMBER Not applicable. FUNDING DECLARATION The authors have no sources of funding to declare. Author Contribution All authors made individual contributions to the authorship. S.S. was involved in the initial diagnosis of the patient and manuscript submission. P.S. and J.S. were involved in the management of the patient and editing the manuscript. All authors reviewed and approved the final draft. ACKNOWLEDGEMENTS No individuals other than the authors contributed to this manuscript. Data Availability All data generated or analysed during this study are included in this published article. References Ghosh C, Luong G, Sun Y. A snapshot of the PD-1/PD-L1 pathway. J Cancer. 2021;12(9):2735–46. Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158–68. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016;375(19):1823–33. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2531–32. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30. 10.1056/NEJMoa1412082 . Johnson DB, Nebhan CA, Moslehi JJ, Balco JM. Immune-checkpoint inhibitors: long-term implications of toxicity. Nat Rev Clin Oncol. 2022;19:254–67. 10.1038/s41571-022-00600-w . Patrinely JR Jr, Johnson R, Lawless AR, et al. Chronic immune-related adverse events following adjuvant anti-PD-1 therapy for high-risk resected melanoma. JAMA Oncol. 2021;7(5):744–48. Barron CC, Stefanova I, Cha Y, et al. Chronic immune-related adverse events in patients with cancer receiving immune checkpoint inhibitors: a systematic review. J Immunother Cancer. 2023;11(8):e006500. Schulz TU, Zierold S, Sachse MM, et al. Persistent immune-related adverse events after cessation of checkpoint inhibitor therapy: Prevalence and impact on patients' health-related quality of life. Eur J Cancer. 2022;176:88–99. Fisher L, Polonsky WH, Hessler DM. Understanding the sources of diabetes distress in adults with type 1 diabetes. J Diabetes Complicat. 2015;29(4):572–7. Holt RIG, DeVries JH, Hess-Fischl A, et al. The Management of Type 1 Diabetes in Adults. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2021;44(11):2589–625. Corriere M, Rooparinesingh N, Kalyani RR. Epidemiology of diabetes and diabetes complications in the elderly: an emerging public health burden. Curr Diab Rep. 2013;13(6):805–13. Young-Hyman D, de Groot M, Hill-Briggs F, Gonzalez JS, Hood K, Peyrot M. Psychosocial Care for People With Diabetes: A Position Statement of the American Diabetes Association. Diabetes Care. 2016;39(12):2126–40. van Holstein Y, Kapiteijn E, Bastiaannet E, van den Bos F, Portielje J, de Glas NA. Efficacy and Adverse Events of Immunotherapy with Checkpoint Inhibitors in Older Patients with Cancer. Drugs Aging. 2019;36(10):927–38. Marseglia A, Wang HX, Rizzuto D, Fratiglioni L, Xu W. Participating in Mental, Social, and Physical Leisure Activities and Having a Rich Social Network Reduce the Incidence of Diabetes-Related Dementia in a Cohort of Swedish Older Adults. Diabetes Care. 2019;42(2):232–9. Schneider BJ, Naidoo J, Santomasso BD, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. J Clin Oncol. 2021;39(36):4073–126. de Filette JMK, Pen JJ, Decoster L, et al. Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review. Eur J Endocrinol. 2019;181(3):363–74. Tables Table 1. Estimated incidence (%) of acute and chronic irAEs in anti-PD1 therapy. Data from initial clinical trials is available in the first 3 columns (3, 4, 5), compared to a more recent retrospective study assessing the incidence of acute and chronic (persisting >12 weeks) irAEs in patients receiving adjuvant anti-PD1 treatment (7). Of note, this data is available in open access journals. *N/D = Not determined. ACUTE CHRONIC irAE KEYNOTE -024 (3) n =154 KEYNOTE -006 (4) n =555 CHECKMATE -066 (5) n =206 Patrinley et al, 2021 (7) n =387 Patrinley et al, 2021 (7) n =387 Endocrine Diabetes 0.6 0.4 0.5 0.5 0.3 Hypothyroidism 9.1 9.4 4.4 16.3 14 Hyperthyroidism 7.8 4.9 3.4 N/D N/D Hypophysitis 0.6 0.5 0.5 2.1 2.1 Nonendocrine Pneumonitis 5.8 1.1 1.5 4.4 1.6 Colitis 1.9 2.7 1.0 9.8 1.6 Myositis 1.9 0.4 N/D* 0.5 0 Hepatitis N/D 1.4 3.4 6.2 1.0 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 23 Dec, 2025 Reviews received at journal 22 Dec, 2025 Reviews received at journal 19 Dec, 2025 Reviewers agreed at journal 19 Dec, 2025 Reviewers agreed at journal 18 Dec, 2025 Reviewers agreed at journal 10 Dec, 2025 Reviewers invited by journal 05 Dec, 2025 Editor invited by journal 26 Nov, 2025 Editor assigned by journal 26 Nov, 2025 Submission checks completed at journal 25 Nov, 2025 First submitted to journal 25 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8149829","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":555708812,"identity":"058f9e46-f77b-403a-8860-59df6f61326a","order_by":0,"name":"Stephanie Saey","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBklEQVRIiWNgGAWjYFADCSBOYLCB8tgIqjeAaUkjVQsDw2HCWuTbDx+TYPjzR85cuvnZgwcV56P5ZyQfYPhQdhinFoMzaWkSjG0GxpZzjpkbJJy5nTvjRloC44xzeLQw5JhJMDYYJG64kWAmkdh2O7fhRo4BM28bbi3y/e+/AR1mUL/hRvo3icR/53Lng7T8xaOF4UYOmwQDm0GCwQ2gdYkNB3I3gLQw4tFicOOZsUVim7Hhzhk5ZRIJx5JzN555lnCw51w6HoclP7zx4Y+cvLlE+jbJHzV2ufOOJx988KPMGrfDGBhYJBLA4QADAgkMB/CpBwLmDwwoWvgJaRgFo2AUjIKRBgDmCVu+P5HdwgAAAABJRU5ErkJggg==","orcid":"","institution":"Mayo Clinic","correspondingAuthor":true,"prefix":"","firstName":"Stephanie","middleName":"","lastName":"Saey","suffix":""},{"id":555708813,"identity":"5c311dc6-e6de-481f-8d47-60d9d30564cf","order_by":1,"name":"Jas Sara","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Jas","middleName":"","lastName":"Sara","suffix":""},{"id":555708814,"identity":"cc62e481-2c54-4cae-a115-267132dab62d","order_by":2,"name":"Pankaj Shah","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Pankaj","middleName":"","lastName":"Shah","suffix":""}],"badges":[],"createdAt":"2025-11-19 02:08:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8149829/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8149829/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97663071,"identity":"2f5b423c-b96f-4083-9cdb-1f463be0d0a6","added_by":"auto","created_at":"2025-12-08 08:21:55","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":432812,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptforDiscoverMedrevised1124251.docx","url":"https://assets-eu.researchsquare.com/files/rs-8149829/v1/6f3b612833ba3893c4d48916.docx"},{"id":97663069,"identity":"40c5013c-b591-4c2d-bd1e-7ca8da82f082","added_by":"auto","created_at":"2025-12-08 08:21:54","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4573,"visible":true,"origin":"","legend":"","description":"","filename":"78b1b33b315245589d8b174d326cb35b.json","url":"https://assets-eu.researchsquare.com/files/rs-8149829/v1/93fa227fe14856089469e2ca.json"},{"id":97663066,"identity":"49ad1404-6af1-4213-9600-09ef8feeb746","added_by":"auto","created_at":"2025-12-08 08:21:54","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":44371,"visible":true,"origin":"","legend":"","description":"","filename":"78b1b33b315245589d8b174d326cb35b1enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8149829/v1/1621941dab3e43bf724673e3.xml"},{"id":97674629,"identity":"e9a66b74-1802-44ea-b254-90e0e8f38f71","added_by":"auto","created_at":"2025-12-08 09:43:44","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":42865,"visible":true,"origin":"","legend":"","description":"","filename":"78b1b33b315245589d8b174d326cb35b1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8149829/v1/13a50d6b0d60f9af1b88ea63.xml"},{"id":97663070,"identity":"ea589ef7-d587-4f5d-8d86-dd1f220200ac","added_by":"auto","created_at":"2025-12-08 08:21:54","extension":"html","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":48174,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8149829/v1/9cb7885bb03c6fb003ac3174.html"},{"id":97678869,"identity":"10bd2f96-5091-4d40-b766-6209becb6c3b","added_by":"auto","created_at":"2025-12-08 09:56:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":372163,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8149829/v1/75bc7794-78cc-48f0-9db5-b4865367e3ae.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Immune checkpoint inhibitor-induced diabetes leading to distress and worsening quality of life: A case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eImmune checkpoint inhibitors (ICIs) have transformed cancer treatment over the last decade. Pembrolizumab is an ICI that inhibits Programmed cell death protein 1 (PD-1) on T cells, a receptor often upregulated in cancers to evade immune destruction. In binding to PD-1, Pembrolizumab releases the brakes on T-cell activation to restore immune function (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). This mechanism makes Pembrolizumab an effective antitumor agent but also predisposes individuals to many autoimmune complications. Termed immune-related adverse events (irAEs), these toxicities affect a variety of organs, manifesting as endocrinopathies, colitis, hepatitis, and nephritis, among others (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Many irAEs are acute and self-limiting, but chronic sequelae are underreported, particularly their impact on quality of life. This gap in understanding is critical when guiding shared decision making, and when working with older individuals who may be more vulnerable. Here we highlight a case of an 86-year-old woman who developed significant distress upon being diagnosed with new-onset diabetes presenting as diabetic ketoacidosis (DKA) while undergoing Pembrolizumab therapy for non-small cell lung cancer (NSCLC).\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eAn 86-year-old white female presented to the Emergency Department (ED) with a six-day history of progressively worsening nausea, anorexia, weakness, “brain fog,” polydipsia, and polyuria. She denied abdominal pain, diarrhea, vomiting, flu-like illness, upper respiratory infection, or corticosteroid use. The patient had recently been diagnosed with Stage IV non-small cell lung adenocarcinoma, poorly differentiated (PD-L1 100%, KRAS G12V-positive). She had begun Pembrolizumab 2mg for palliative intent, receiving cycle #2 two weeks prior to presentation. Immunotherapy was chosen as she did not have a targetable alteration. She had declined radiation therapy, wishing to avoid side efects and “preserve [my] quality of life.”\u003c/p\u003e\u003cp\u003eA widow of 18 years, the patient reported living alone but was active in the community and enjoyed meeting friends for lunch and being part of breakfast clubs. Despite having Stage IV cancer, she was quoted as feeling “great” at the time of her oncology appointments. Baseline endocrine workup was significant for prediabetes (A1c 5.9%) and subclinical hypothyroidism (TSH 5.8 mIU/L). Other blood tests were unremarkable. She had fibromyalgia, obesity (BMI 35 kg/m2), and well-controlled hypertension. Her only medication was Pembrolizumab.\u003c/p\u003e\u003cp\u003eOn arrival, she was afebrile and hemodynamically stable though slightly tachypneic (respiratory rate 22). Laboratory evaluation confirmed DKA: glucose of 24.48 mmol/L, venous blood gas pH 7.14, bicarbonate 14 mmol/L, anion gap 18, and beta hydroxybutyrate 6.2 mmol/L. Workup for secondary causes of DKA was negative. Pembrolizumab-induced DKA was diagnosed. She received intravenous insulin and fluids, improved, and was transitioned to multiple daily insulin injection (MDI) insulin therapy. Insulin deficiency was documented with undetectable C-peptide was \u0026lt; 0.1 when plasma glucose was 204.\u003c/p\u003e\u003cp\u003eShe established Endocrinology follow-up and continues to struggle with glycemic control. Current management includes continuous glucose monitoring and 4–5 daily injections. Each meal requires carbohydrate estimation, glucose review, and bolus dose calculation. She follows up every 2–3 months and contacts diabetes educators nearly every other week.\u003c/p\u003e\u003cp\u003eDespite an excellent Positron Emission Tomography scan response, she declined further Pembrolizumab, describing being “scared to death” of additional cycles. The diabetes diagnosis caused profound psychological burden, which she described as “traumatic.” Her GAD-7 score worsened from 6 (mild anxiety) pre-treatment to 15 (severe anxiety). She has begun therapy to cope with her anxiety.\u003c/p\u003e"},{"header":"Discussions and Conclusion","content":"\u003cp\u003eKnowledge of irAEs is growing amidst the widespread use of ICIs (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Early clinical trials and subsequent studies, including case reports, have focused on recognizing acute, life-threatening irAEs and physiological risk factors (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). While critical, this emphasis has overshadowed the broader spectrum of toxicities, especially those with chronic, long-term quality-of-life impact. As real-world data accumulates, recognition of chronic irAEs is increasing, but they remain underreported in clinical trials (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). The Table below summarizes the incidence of several acute irAEs reported in initial anti–PD-1 trials and contrasts them with a more recent retrospective study that documented both acute and chronic irAEs in patients receiving ICI therapy (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eWhile limited, existing data suggest chronic irAEs are associated with measurable declines in health-related quality of life (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Our case uniquely illustrates the psychological burden of ICI-induced diabetes in an elderly patient. Diabetes increases risks of depression, anxiety, and burnout (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In older adults, these are compounded by vulnerability to complications such as nephropathy, cardiovascular disease, and geriatric syndromes (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). In our patient, daily demands of insulin management and diet contributed to significant distress. The balance of survival benefit versus diminished quality of life becomes especially salient in the context of advanced cancer.\u003c/p\u003e\u003cp\u003eOlder adults are underrepresented in clinical trials, creating gaps in understanding chronic irAEs (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Observational studies suggest irAEs may be especially debilitating in this group due to diminished reserve and comorbidities (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Complex diabetes self-management can interfere with social interaction and exercise, both protective for cognition and mood (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Future studies must prioritize geriatric representation and include patient-centered endpoints such as functional status and quality of life.\u003c/p\u003e\u003cp\u003eClinicians should consider early referral to mental health services and diabetes education as part of the standard management of ICI-induced diabetes, particularly in older adults. Collaborative care models that include behavioral health professionals, diabetes educators, and social workers may improve long-term outcomes and better support patients navigating the dual burden of cancer and chronic endocrine disease (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFinally, this case underscores the importance of comprehensive pre-treatment counseling. While acute risks such as DKA are often discussed, the potential permanence and psychological toll of chronic irAEs may be overlooked (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Counseling should address both physical and emotional demands, especially in older adults, to align treatment with patient values and goals (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAlthough limited by its single-patient focus, this case highlights a clinically significant and underrecognized issue: the long-term psychological and quality of life impact of chronic immune-related adverse events (irAEs) like ICI-induced diabetes in elderly patients. It reinforces the value of case reports in identifying vulnerable populations and informing future patient-centered research. As ICI use expands, particularly in palliative care settings, thorough patient counseling that addresses both physical and emotional burdens is essential to support informed decision-making. Future studies should prioritize geriatric populations and quality-of-life outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eHUMAN ETHICS\u003c/h2\u003e\u003cp\u003eThe requirement of ethical approval for this study was waived by the Mayo Clinic Institutional Review Board and the protocol was conducted in accordance with the ethical standards as larid down in the 1964 Declaration of Helsinki and its later amendments.\u003c/p\u003e\u003ch2\u003eCONSENT TO PARTICIPATE\u003c/h2\u003e\u003cp\u003eInformed consent was obtained from the patient for participation in this study.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCONSENT TO PUBLISH\u003c/strong\u003e\u003cp\u003e Written informed consent for publication was obtained from the patient.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eCLINICAL TRIAL NUMBER\u003c/h2\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFUNDING\u003c/h2\u003e\u003cp\u003eDECLARATION\u003c/p\u003e\u003cp\u003eThe authors have no sources of funding to declare.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors made individual contributions to the authorship. S.S. was involved in the initial diagnosis of the patient and manuscript submission. P.S. and J.S. were involved in the management of the patient and editing the manuscript. All authors reviewed and approved the final draft.\u003c/p\u003e\u003ch2\u003eACKNOWLEDGEMENTS\u003c/h2\u003e\u003cp\u003eNo individuals other than the authors contributed to this manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGhosh C, Luong G, Sun Y. A snapshot of the PD-1/PD-L1 pathway. J Cancer. 2021;12(9):2735\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePostow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eReck M, Rodr\u0026iacute;guez-Abreu D, Robinson AG, Hui R, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016;375(19):1823\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRobert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2531\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRobert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1412082\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa1412082\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJohnson DB, Nebhan CA, Moslehi JJ, Balco JM. Immune-checkpoint inhibitors: long-term implications of toxicity. Nat Rev Clin Oncol. 2022;19:254\u0026ndash;67. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41571-022-00600-w\u003c/span\u003e\u003cspan address=\"10.1038/s41571-022-00600-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePatrinely JR Jr, Johnson R, Lawless AR, et al. Chronic immune-related adverse events following adjuvant anti-PD-1 therapy for high-risk resected melanoma. JAMA Oncol. 2021;7(5):744\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarron CC, Stefanova I, Cha Y, et al. Chronic immune-related adverse events in patients with cancer receiving immune checkpoint inhibitors: a systematic review. J Immunother Cancer. 2023;11(8):e006500.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchulz TU, Zierold S, Sachse MM, et al. Persistent immune-related adverse events after cessation of checkpoint inhibitor therapy: Prevalence and impact on patients' health-related quality of life. Eur J Cancer. 2022;176:88\u0026ndash;99.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFisher L, Polonsky WH, Hessler DM. Understanding the sources of diabetes distress in adults with type 1 diabetes. J Diabetes Complicat. 2015;29(4):572\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHolt RIG, DeVries JH, Hess-Fischl A, et al. The Management of Type 1 Diabetes in Adults. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2021;44(11):2589\u0026ndash;625.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCorriere M, Rooparinesingh N, Kalyani RR. Epidemiology of diabetes and diabetes complications in the elderly: an emerging public health burden. Curr Diab Rep. 2013;13(6):805\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYoung-Hyman D, de Groot M, Hill-Briggs F, Gonzalez JS, Hood K, Peyrot M. Psychosocial Care for People With Diabetes: A Position Statement of the American Diabetes Association. Diabetes Care. 2016;39(12):2126\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Holstein Y, Kapiteijn E, Bastiaannet E, van den Bos F, Portielje J, de Glas NA. Efficacy and Adverse Events of Immunotherapy with Checkpoint Inhibitors in Older Patients with Cancer. Drugs Aging. 2019;36(10):927\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarseglia A, Wang HX, Rizzuto D, Fratiglioni L, Xu W. Participating in Mental, Social, and Physical Leisure Activities and Having a Rich Social Network Reduce the Incidence of Diabetes-Related Dementia in a Cohort of Swedish Older Adults. Diabetes Care. 2019;42(2):232\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchneider BJ, Naidoo J, Santomasso BD, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. J Clin Oncol. 2021;39(36):4073\u0026ndash;126.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ede Filette JMK, Pen JJ, Decoster L, et al. Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review. Eur J Endocrinol. 2019;181(3):363\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Estimated incidence (%) of acute and chronic irAEs in anti-PD1 therapy.\u003c/strong\u003e Data from initial clinical trials is available in the first 3 columns (3, 4, 5), compared to a more recent retrospective study assessing the incidence of acute and chronic (persisting \u0026gt;12 weeks) irAEs in patients receiving adjuvant anti-PD1 treatment (7). Of note, this data is available in open access journals. *N/D = Not determined.\u0026nbsp;\u003c/p\u003e\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"631\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 80.6656%;\"\u003e\n \u003cp\u003eACUTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3344%;\"\u003e\n \u003cp\u003eCHRONIC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6403%;\"\u003e\n \u003cp\u003eirAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7987%;\"\u003e\n \u003cp\u003e\u0026nbsp;KEYNOTE -024 (3)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e=154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9952%;\"\u003e\n \u003cp\u003eKEYNOTE -006 (4)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e=555\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9572%;\"\u003e\n \u003cp\u003eCHECKMATE -066 (5)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e=206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2742%;\"\u003e\n \u003cp\u003ePatrinley et al, 2021 (7)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e=387\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3344%;\"\u003e\n \u003cp\u003ePatrinley et al, 2021 (7)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e=387\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6403%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEndocrine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7987%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9952%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9572%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2742%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3344%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6403%;\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7987%;\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9952%;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9572%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2742%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3344%;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6403%;\"\u003e\n \u003cp\u003eHypothyroidism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7987%;\"\u003e\n \u003cp\u003e9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9952%;\"\u003e\n \u003cp\u003e9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9572%;\"\u003e\n \u003cp\u003e4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2742%;\"\u003e\n \u003cp\u003e16.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3344%;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6403%;\"\u003e\n \u003cp\u003eHyperthyroidism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7987%;\"\u003e\n \u003cp\u003e7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9952%;\"\u003e\n \u003cp\u003e4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9572%;\"\u003e\n \u003cp\u003e3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2742%;\"\u003e\n \u003cp\u003eN/D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3344%;\"\u003e\n \u003cp\u003eN/D\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6403%;\"\u003e\n \u003cp\u003eHypophysitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7987%;\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9952%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9572%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2742%;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3344%;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6403%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNonendocrine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7987%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9952%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9572%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2742%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3344%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6403%;\"\u003e\n \u003cp\u003ePneumonitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7987%;\"\u003e\n \u003cp\u003e5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9952%;\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9572%;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2742%;\"\u003e\n \u003cp\u003e4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3344%;\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6403%;\"\u003e\n \u003cp\u003eColitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7987%;\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9952%;\"\u003e\n \u003cp\u003e2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9572%;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2742%;\"\u003e\n \u003cp\u003e9.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3344%;\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6403%;\"\u003e\n \u003cp\u003eMyositis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7987%;\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9952%;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9572%;\"\u003e\n \u003cp\u003eN/D*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2742%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3344%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6403%;\"\u003e\n \u003cp\u003eHepatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7987%;\"\u003e\n \u003cp\u003eN/D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9952%;\"\u003e\n \u003cp\u003e1.4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.9572%;\"\u003e\n \u003cp\u003e3.4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2742%;\"\u003e\n \u003cp\u003e6.2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3344%;\"\u003e\n \u003cp\u003e1.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"diabetic ketoacidosis, diabetes, immune checkpoint inhibitor, immune related adverse events, case report","lastPublishedDoi":"10.21203/rs.3.rs-8149829/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8149829/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAn 86-year-old woman with metastatic non-small cell lung carcinoma on Pembrolizumab presented to the Emergency Department with diabetic ketoacidosis; after appropriate treatment she was transitioned to basal/bolus insulin regimen. She had chosen to receive Immune Checkpoint Inhibitor (ICI) instead of radiotherapy, as she wished to preserve her quality of life. With the demands of management of ICI-induced irreversible insulin deficient diabetes she now has substantial worsening of quality of life with considerable anxiety and depressed mood. ICI-induced diabetes and DKA is more common in patients treated with Pembrolizumab than suggested by early trials. In addition to highlighting the importance of counseling patients on the signs and symptoms of hyperglycemia for earlier detection, our case calls for considering the psychological impact of managing a chronic illness in patient education prior to initiating ICI therapy.\u003c/p\u003e","manuscriptTitle":"Immune checkpoint inhibitor-induced diabetes leading to distress and worsening quality of life: A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-08 08:21:50","doi":"10.21203/rs.3.rs-8149829/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-23T08:07:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-22T19:07:48+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-19T13:21:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"174393334719900556177176900614506385203","date":"2025-12-19T09:15:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"20649741918132143932972443072527620388","date":"2025-12-18T21:10:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"270961572055266488194250478379722854808","date":"2025-12-10T17:15:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-05T06:25:38+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-26T14:14:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-26T09:32:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-25T16:36:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Medicine","date":"2025-11-25T16:29:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e53fd3c9-0079-4111-b7dd-64d7f024f1d5","owner":[],"postedDate":"December 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T13:38:54+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-08 08:21:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8149829","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8149829","identity":"rs-8149829","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}