{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:46:18Z","timestamp":1792125978517,"version":"4.4.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":102,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Ment Health"],"DOI":"10.1007\/s44192-026-00518-0","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T06:25:28Z","timestamp":1783319128000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated cortisol in patients with type 2 diabetes mellitus and comorbid depressive symptoms is associated with poor glycemic control and reduced insulin levels"],"prefix":"10.1007","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0517-247X","authenticated-orcid":false,"given":"Uzair","family":"Abbas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabeel Nawaz","family":"Laghari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misha","family":"Tanveer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usama Abdul","family":"Musawwir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Ahsan","family":"Zafar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhib Ullah","family":"Khalid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Hadif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israr","family":"Baloch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashaf","family":"Fatima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fizza","family":"Abid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"issue":"2","key":"518_CR1","doi-asserted-by":"publisher","first-page":"36","DOI":"10.3390\/diabetology2020004","volume":"2","author":"S Alam","year":"2021","unstructured":"Alam S, Hasan MK, Neaz S, Hussain N, Hossain MF, Rahman T. Diabetes Mellitus: insights from epidemiology, biochemistry, risk factors, diagnosis, complications and comprehensive management. Diabetology. 2021;2(2):36\u201350.","journal-title":"Diabetology"},{"issue":"5","key":"518_CR2","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/S2213-8587(22)00102-4","volume":"10","author":"ZA Bhutta","year":"2022","unstructured":"Bhutta ZA, Haq ZU, Basit A. Diabetes in Pakistan: addressing the crisis. Lancet Diabetes Endocrinol. 2022;10(5):309\u201310.","journal-title":"Lancet Diabetes Endocrinol"},{"key":"518_CR3","doi-asserted-by":"publisher","first-page":"110991","DOI":"10.1016\/j.jpsychores.2022.110991","volume":"162","author":"AG Mersha","year":"2022","unstructured":"Mersha AG, Tollosa DN, Bagade T, Eftekhari P. A bidirectional relationship between diabetes mellitus and anxiety: A systematic review and meta-analysis. J Psychosom Res. 2022;162:110991.","journal-title":"J Psychosom Res"},{"issue":"19","key":"518_CR4","doi-asserted-by":"publisher","first-page":"4226","DOI":"10.3390\/nu15194226","volume":"15","author":"R Basiri","year":"2023","unstructured":"Basiri R, Seidu B, Rudich M. Exploring the interrelationships between diabetes, nutrition, anxiety, and depression: implications for treatment and prevention strategies. Nutrients. 2023;15(19):4226.","journal-title":"Nutrients"},{"issue":"6","key":"518_CR5","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1111\/dme.13606","volume":"35","author":"K Smith","year":"2018","unstructured":"Smith K, Desch\u00eanes SS, Schmitz N. Investigating the longitudinal association between diabetes and anxiety: a systematic review and meta-analysis. Diabet Med. 2018;35(6):677\u201393.","journal-title":"Diabet Med"},{"key":"518_CR6","doi-asserted-by":"publisher","first-page":"100720","DOI":"10.1016\/j.jadr.2024.100720","volume":"16","author":"B Chireh","year":"2024","unstructured":"Chireh B, Essien SK, D\u2019Arcy C, Gyan C, Ankrah M. Severe disability and self-reported depression and anxiety among persons living with Type 2 diabetes in Canada. J Affect disorders Rep. 2024;16:100720.","journal-title":"J Affect disorders Rep"},{"key":"518_CR7","doi-asserted-by":"publisher","first-page":"1282249","DOI":"10.3389\/fpsyt.2023.1282249","volume":"14","author":"SA Abualhamael","year":"2024","unstructured":"Abualhamael SA, Baig M, Alghamdi W, Gazzaz ZJ, Al-Hayani M, Bazi A. Quality of life, stress, anxiety and depression and associated factors among people with type 2 diabetes mellitus in Western region Saudi Arabia. Front Psychiatry. 2024;14:1282249.","journal-title":"Front Psychiatry"},{"issue":"1","key":"518_CR8","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.neubiorev.2011.10.001","volume":"36","author":"MJ Stuart","year":"2012","unstructured":"Stuart MJ, Baune BT. Depression and type 2 diabetes: inflammatory mechanisms of a psychoneuroendocrine co-morbidity. Neurosci Biobehavioral Reviews. 2012;36(1):658\u201376.","journal-title":"Neurosci Biobehavioral Reviews"},{"issue":"3","key":"518_CR9","doi-asserted-by":"publisher","first-page":"283","DOI":"10.5498\/wjp.v6.i3.283","volume":"6","author":"SW Jeon","year":"2016","unstructured":"Jeon SW, Kim YK. Neuroinflammation and cytokine abnormality in major depression: Cause or consequence in that illness? World J Psychiatry. 2016;6(3):283\u201393.","journal-title":"World J Psychiatry"},{"key":"518_CR10","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.lfs.2017.06.025","volume":"183","author":"GZ Reus","year":"2017","unstructured":"Reus GZ, Dos Santos MAB, Strassi AP, Abelaira HM, Ceretta LB, Quevedo J. Pathophysiological mechanisms involved in the relationship between diabetes and major depressive disorder. Life Sci. 2017;183:78\u201382.","journal-title":"Life Sci"},{"issue":"9","key":"518_CR11","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/j.psyneuen.2011.03.005","volume":"36","author":"JK Rustad","year":"2011","unstructured":"Rustad JK, Musselman DL, Nemeroff CB. The relationship of depression and diabetes: pathophysiological and treatment implications. Psychoneuroendocrinology. 2011;36(9):1276\u201386.","journal-title":"Psychoneuroendocrinology"},{"issue":"2","key":"518_CR12","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.jpsychores.2014.11.018","volume":"78","author":"AN Niles","year":"2015","unstructured":"Niles AN, Dour HJ, Stanton AL, Roy-Byrne PP, Stein MB, Sullivan G, et al. Anxiety and depressive symptoms and medical illness among adults with anxiety disorders. J Psychosom Res. 2015;78(2):109\u201315.","journal-title":"J Psychosom Res"},{"issue":"1","key":"518_CR13","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1186\/s13098-024-01515-5","volume":"16","author":"Y Liang","year":"2024","unstructured":"Liang Y, Liang J, Jiang W, Wang W, Yang X, Liu Y, et al. Stronger association between morning serum cortisol level and diurnal time in range in type 2 diabetes? Diabetol Metab Syndr. 2024;16(1):290.","journal-title":"Diabetol Metab Syndr"},{"issue":"1","key":"518_CR14","doi-asserted-by":"publisher","first-page":"e003218","DOI":"10.1136\/bmjdrc-2022-003218","volume":"12","author":"P Mosili","year":"2024","unstructured":"Mosili P, Mkhize BC, Sibiya NH, Ngubane PS, Khathi A. Review of the direct and indirect effects of hyperglycemia on the HPA axis in T2DM and the co-occurrence of depression. BMJ Open Diabetes Res Care. 2024;12(1):e003218.","journal-title":"BMJ Open Diabetes Res Care"},{"issue":"15","key":"518_CR15","doi-asserted-by":"publisher","first-page":"8178","DOI":"10.3390\/ijms23158178","volume":"23","author":"JAMJL Janssen","year":"2022","unstructured":"Janssen JAMJL. New Insights into the Role of Insulin and Hypothalamic-Pituitary-Adrenal (HPA) Axis in the Metabolic Syndrome. Int J Mol Sci. 2022;23(15):8178.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"518_CR16","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1111\/nyas.13217","volume":"1391","author":"JJ Joseph","year":"2017","unstructured":"Joseph JJ, Golden SH. Cortisol dysregulation: the bidirectional link between stress, depression, and type 2 diabetes mellitus. Ann N Y Acad Sci. 2017;1391(1):20\u201334.","journal-title":"Ann N Y Acad Sci"},{"issue":"12","key":"518_CR17","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1016\/j.eprac.2021.07.014","volume":"27","author":"C Aresta","year":"2021","unstructured":"Aresta C, Soranna D, Giovanelli L, Favero V, Parazzoli C, Gennari L, et al. When to suspect hidden hypercortisolism in type 2 diabetes: a meta-analysis. Endocr Pract. 2021;27(12):1216\u201324.","journal-title":"Endocr Pract"},{"issue":"2","key":"518_CR18","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3758\/BF03193146","volume":"39","author":"F Faul","year":"2007","unstructured":"Faul F, Erdfelder E, Lang A-G, Buchner A. G* Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175\u201391.","journal-title":"Behav Res Methods"},{"issue":"6","key":"518_CR19","doi-asserted-by":"publisher","first-page":"746","DOI":"10.4103\/2230-8210.192924","volume":"20","author":"R Rajput","year":"2016","unstructured":"Rajput R, Gehlawat P, Gehlan D, Gupta R, Rajput M. Prevalence and predictors of depression and anxiety in patients of diabetes mellitus in a tertiary care center. Indian J Endocrinol Metabol. 2016;20(6):746\u201351.","journal-title":"Indian J Endocrinol Metabol"},{"issue":"1","key":"518_CR20","first-page":"43","volume":"8","author":"A Kokoszka","year":"2008","unstructured":"Kokoszka A. Depression in diabetes self-rating scale: a screening tool. Diabetologia. 2008;8(1):43\u20137.","journal-title":"Diabetologia"},{"key":"518_CR21","doi-asserted-by":"publisher","first-page":"1135964","DOI":"10.3389\/fpubh.2023.1135964","volume":"11","author":"H Sharif","year":"2023","unstructured":"Sharif H, Jan SS, Sharif S, Seemi T, Naeem H, Jawed Z. Depression and suicidal ideation among individuals with type-2 diabetes mellitus, a cross-sectional study from an urban slum area of Karachi, Pakistan. Front public health. 2023;11:1135964.","journal-title":"Front public health"},{"issue":"13","key":"518_CR22","doi-asserted-by":"publisher","first-page":"6929","DOI":"10.3390\/ijerph18136929","volume":"18","author":"\u00c1 Fuentes-Merlos","year":"2021","unstructured":"Fuentes-Merlos \u00c1, Orozco-Beltr\u00e1n D, Quesada Rico JA, Reina R. Quality-of-life determinants in people with diabetes mellitus in Europe. Int J Environ Res Public Health. 2021;18(13):6929.","journal-title":"Int J Environ Res Public Health"},{"issue":"12","key":"518_CR23","doi-asserted-by":"publisher","first-page":"2066","DOI":"10.1007\/s00125-022-05764-9","volume":"65","author":"J Dibato","year":"2022","unstructured":"Dibato J, Montvida O, Ling J, Koye D, Polonsky WH, Paul SK. Temporal trends in the prevalence and incidence of depression and the interplay of comorbidities in patients with young-and usual-onset type 2 diabetes from the USA and the UK. Diabetologia. 2022;65(12):2066\u201377.","journal-title":"Diabetologia"},{"issue":"5","key":"518_CR24","doi-asserted-by":"publisher","first-page":"e0323126","DOI":"10.1371\/journal.pone.0323126","volume":"20","author":"U Abbas","year":"2025","unstructured":"Abbas U, Hussain N, Tanveer M, Laghari RN, Ahmed I, Rajper AB. Frequency and predictors of depression and anxiety in chronic illnesses: A multi disease study across non-communicable and communicable diseases. PLoS ONE. 2025;20(5):e0323126.","journal-title":"PLoS ONE"},{"issue":"2","key":"518_CR25","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s12020-016-1108-1","volume":"54","author":"H Raff","year":"2016","unstructured":"Raff H, Magill SB. Is the hypothalamic\u2013pituitary\u2013adrenal axis disrupted in type 2 diabetes mellitus? Endocrine. 2016;54(2):273\u20135.","journal-title":"Endocrine"},{"issue":"2","key":"518_CR26","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1046\/j.1365-2796.2000.00603.x","volume":"247","author":"P Rosmond Ra, Bj\u00f6rntorp","year":"2000","unstructured":"Rosmond Ra, Bj\u00f6rntorp P. The hypothalamic\u2013pituitary\u2013adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke. J Intern Med. 2000;247(2):188\u201397.","journal-title":"J Intern Med"},{"issue":"7","key":"518_CR27","doi-asserted-by":"publisher","first-page":"976","DOI":"10.4103\/0366-6999.154323","volume":"128","author":"L-Y Yu","year":"2015","unstructured":"Yu L-Y, Pei Y. Insulin Neuroprotection and the Mechanisms. Chin Med J. 2015;128(7):976\u201381.","journal-title":"Chin Med J"},{"issue":"6","key":"518_CR28","first-page":"994","volume":"1783","author":"AI Duarte","year":"2008","unstructured":"Duarte AI, Santos P, Oliveira CR, Santos MS, Rego AC. Insulin neuroprotection against oxidative stress is mediated by Akt and GSK-3\u03b2 signaling pathways and changes in protein expression. Biochimica et Biophysica Acta (BBA) -. Mol Cell Res. 2008;1783(6):994\u20131002.","journal-title":"Mol Cell Res"},{"key":"518_CR29","doi-asserted-by":"crossref","unstructured":"Mielke JG, Wang Y-T. Chapter 4 - Insulin, Synaptic Function, and Opportunities for Neuroprotection. In: Rahman S, editor. Progress in Molecular Biology and Translational Science. Academic. 2011;98:133\u201386.","DOI":"10.1016\/B978-0-12-385506-0.00004-1"},{"key":"518_CR30","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/bs.irn.2019.11.006","volume":"152","author":"DB O\u2019Connor","year":"2020","unstructured":"O\u2019Connor DB, Gartland N, O\u2019Connor RC. Stress, cortisol and suicide risk. Int Rev Neurobiol. 2020;152:101\u201330.","journal-title":"Int Rev Neurobiol"},{"key":"518_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.expneurol.2019.01.016","volume":"315","author":"JA Hamer","year":"2019","unstructured":"Hamer JA, Testani D, Mansur RB, Lee Y, Subramaniapillai M, McIntyre RS. Brain insulin resistance: A treatment target for cognitive impairment and anhedonia in depression. Exp Neurol. 2019;315:1\u20138.","journal-title":"Exp Neurol"},{"issue":"5","key":"518_CR32","doi-asserted-by":"publisher","first-page":"e12806","DOI":"10.1111\/cpr.12806","volume":"53","author":"XH Zou","year":"2020","unstructured":"Zou XH, Sun LH, Yang W, Li BJ, Cui RJ. Potential role of insulin on the pathogenesis of depression. Cell Prolif. 2020;53(5):e12806.","journal-title":"Cell Prolif"},{"key":"518_CR33","unstructured":"Britneff E, Winkley K. The role of psychological interventions for people with diabetes and mental health issues. J Diabetes Nurs. 2013;17(8):305\u201310."},{"issue":"6","key":"518_CR34","first-page":"2010","volume":"2","author":"B Bush","year":"2010","unstructured":"Bush B, Hudson T. The role of cortisol in sleep. Nat Med J. 2010;2(6):2010\u201306.","journal-title":"Nat Med J"},{"issue":"1","key":"518_CR35","first-page":"759234","volume":"2010","author":"M Balbo","year":"2010","unstructured":"Balbo M, Leproult R, Van Cauter E. Impact of sleep and its disturbances on hypothalamo-pituitary\u2010adrenal axis activity. Int J Endocrinol. 2010;2010(1):759234.","journal-title":"Int J Endocrinol"}],"container-title":["Discover Mental Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s44192-026-00518-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s44192-026-00518-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s44192-026-00518-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:08:44Z","timestamp":1792123724000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s44192-026-00518-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,6]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["518"],"URL":"https:\/\/doi.org\/10.1007\/s44192-026-00518-0","relation":{},"ISSN":["2731-4383"],"issn-type":[{"value":"2731-4383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,6]]},"assertion":[{"value":"15 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethical approval was obtained from the Institutional Review Board of Dow University of Health Sciences (IRB number 2839\/DUHS\/Approval\/2022\/176). The study was conducted as per ethical guidelines of declaration of Helsinki.The participants were recruited in the study after written informed consent.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"196"}}