{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:34:29Z","timestamp":1786354469676,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"crossref","award":["503\/8-072-04\/503-81-001"],"award-info":[{"award-number":["503\/8-072-04\/503-81-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"crossref"}]},{"award":["503\/8-072-04\/503-81-001"],"award-info":[{"award-number":["503\/8-072-04\/503-81-001"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>While many studies indicate a bidirectional relationship between type 2 diabetes (T2DM) and depression, its precise nature remains unclear. The aim of the study was to determine the levels of inflammatory markers in oldest-old patients with diabetes and depressive symptoms and identify the risk factors associated with late-life depressive symptoms. In total, 195 participants with diabetes, aged 85 and above, were screened for depressive symptoms using the 30-item Geriatric Depression Scale (GDS-30). Clinical and biochemical data were also collected. Serum levels of inflammatory markers were measured via enzyme-linked immunosorbent assay (ELISA). Serum levels of TNF-\u03b1, IL-1\u03b2, and IL-6 were increased in individuals with depression and correlated with each other as well as with HbA1c levels, GDS scores, FBG and BMI. The multivariable analysis confirmed that of the three studied biomarkers, only TNF-\u03b1 is independently associated with depressive symptoms when adjusting for demographic factors (Model 1) and cardiovascular burden (Model 3); however, its significance disappeared when controlling for glycaemic parameters (Model 2). Only TNF-\u03b1 is independently associated with depressive symptoms in oldest-old patients with T2DM, though this relationship is tightly dependent on glycaemic control. Future studies should clarify whether IL-1\u03b2 and IL-6 contribute to depressive symptoms through distinct pathophysiological pathways.<\/jats:p>","DOI":"10.3390\/ijms27156975","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:16:27Z","timestamp":1785766587000},"page":"6975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammatory Factors Associated with Late-Life Depressive Symptoms in Oldest-Old Patients with Type 2 Diabetes"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0065-4376","authenticated-orcid":false,"given":"Malgorzata","family":"Gorska-Ciebiada","sequence":"first","affiliation":[{"name":"Department of Propaedeutics of Lifestyle Diseases, Medical University of Lodz, ul. Jaracza 63, 90-251 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Ciebiada","sequence":"additional","affiliation":[{"name":"Department of General and Oncological Pulmonology, Medical University of Lodz, 90-549 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Federation (2025). IDF Diabetes Atlas, IDF. [11th ed.]. Available online: https:\/\/diabetesatlas.org\/resources\/idf-diabetes-atlas-2025\/."},{"key":"ref_2","unstructured":"Centers for Disease Control and Prevention (2026, June 20). National Diabetes Statistics Report Website, Available online: https:\/\/usdss.cdc.gov\/diabetes\/report.html."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"119467","DOI":"10.1016\/j.jad.2025.119467","article-title":"The Bidirectional Influence between Type 2 Diabetes Mellitus and the State of Depression and Anxiety","volume":"386","author":"Xu","year":"2025","journal-title":"J. Affect. Disord."},{"key":"ref_4","first-page":"546","article-title":"Chronic Stress and Diabetes Mellitus: Interwoven Pathologies","volume":"16","author":"Sharma","year":"2020","journal-title":"Curr. Diabetes Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.1111\/ejn.15136","article-title":"Pathophysiology Linking Depression and Type 2 Diabetes: Psychotherapy, Physical Exercise, and Fecal Microbiome Transplantation as Damage Control","volume":"53","author":"Subba","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"E313","DOI":"10.1503\/jpn.210036","article-title":"Can treatment of obesity reduce depression or vice versa?","volume":"46","author":"Borgland","year":"2021","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109227","DOI":"10.1016\/j.diabres.2022.109227","article-title":"Associations between Depression and Cognition, Mild Cognitive Impairment and Dementia in Persons with Diabetes Mellitus: A Systematic Review and Meta-Analysis","volume":"185","author":"Chow","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kim, D.J., Yu, J.H., Shin, M.S., Shin, Y.W., and Kim, M.S. (2016). Hyperglycemia Reduces Efficiency of Brain Networks in Subjects with Type 2 Diabetes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157268"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/sj.mp.4000712","article-title":"Adult brain neurogenesis and psychiatry: A novel theory of depression","volume":"5","author":"Jacobs","year":"2000","journal-title":"Mol. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Maydych, V. (2019). The Interplay Between Stress, Inflammation, and Emotional Attention: Relevance for Depression. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00384"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gorska-Ciebiada, M., Saryusz-Wolska, M., Borkowska, A., Ciebiada, M., and Loba, J. (2015). Serum Levels of Inflammatory Markers in Depressed Elderly Patients with Diabetes and Mild Cognitive Impairment. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120433"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1176\/appi.ajp.2015.15020152","article-title":"Inflammation: Depression Fans the Flames and Feasts on the Heat","volume":"172","author":"Derry","year":"2015","journal-title":"Am. J. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110931","DOI":"10.1016\/j.pnpbp.2023.110931","article-title":"Pro-Inflammatory Cytokines in Stress-Induced Depression: Novel Insights into Mechanisms and Promising Therapeutic Strategies","volume":"131","author":"Chang","year":"2024","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1002\/gps.2672","article-title":"The Inflammation Hypothesis in Geriatric Depression","volume":"26","author":"Alexopoulos","year":"2011","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s11920-012-0279-6","article-title":"Biological Basis of Late Life Depression","volume":"14","author":"Disabato","year":"2012","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"C\u0103t\u0103lina, G.R., Gheorman, V., Gheorman, V., and For\u021bofoiu, M.C. (2025). The Role of Neuroinflammation in the Comorbidity of Psychiatric Disorders and Internal Diseases. Healthcare, 13.","DOI":"10.3390\/healthcare13070837"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1111\/dom.15630","article-title":"Depression and Type 2 Diabetes: A Causal Relationship and Mechanistic Pathway","volume":"26","author":"Khawagi","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.biopsych.2009.09.033","article-title":"A meta-analysis of cytokines in major depression","volume":"67","author":"Dowlati","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.arr.2010.11.002","article-title":"Inflammatory Markers in Population Studies of Aging","volume":"10","author":"Singh","year":"2011","journal-title":"Ageing Res. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.biopsych.2018.12.020","article-title":"Longitudinal Association Between Depression and Inflammatory Markers: Results from the Netherlands Study of Depression and Anxiety","volume":"85","author":"Lamers","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Didion, S.P. (2017). Cellular and Oxidative Mechanisms Associated with Interleukin-6 Signaling in the Vasculature. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122563"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1046\/j.1365-2249.2000.01281.x","article-title":"Ageing, Tumour Necrosis Factor-Alpha (TNF-Alpha) and Atherosclerosis","volume":"121","author":"Bruunsgaard","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tripathy, M., Swain, J., and Das, S. (2026). The Association of Diabetes and Atherosclerosis: Understanding the Molecular Mechanism of the Double Burden. Curr. Med. Chem., Online ahead of print.","DOI":"10.2174\/0109298673435173260213113630"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.exger.2007.01.011","article-title":"Inflammation and Interleukin-1 Signaling Network Contribute to Depressive Symptoms but Not Cognitive Decline in Old Age","volume":"42","author":"Biggelaar","year":"2007","journal-title":"Exp. Gerontol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.psyneuen.2012.02.006","article-title":"Inflammatory Biomarkers Predict Depressive, but Not Anxiety Symptoms during Aging: The Prospective Sydney Memory and Aging Study","volume":"37","author":"Baune","year":"2012","journal-title":"Psychoneuroendocrinology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1159\/000261644","article-title":"Blood Inflammatory Proteins and Risk of Incident Depression in the Elderly","volume":"29","author":"Forti","year":"2010","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Cengotitabengoa, M., Carrasc\u00f3n, L., O\u2019Brien, J.T., D\u00edaz-Guti\u00e9rrez, M.J., Berm\u00fadez-Ampudia, C., Sanada, K., Arrasate, M., and Gonz\u00e1lez-Pinto, A. (2016). Peripheral Inflammatory Parameters in Late-Life Depression: A Systematic Review. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122022"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14671","DOI":"10.1111\/dme.14671","article-title":"The Bidirectional Longitudinal Association between Depressive Symptoms and HbA1c: A Systematic Review and Meta-Analysis","volume":"39","author":"Beran","year":"2022","journal-title":"Diab. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jad.2003.08.003","article-title":"Geriatric Depression and Vascular Diseases: What Are the Links?","volume":"81","author":"Camus","year":"2004","journal-title":"J. Affect. Disord."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1001\/archpsyc.61.4.369","article-title":"Relationship between Atherosclerosis and Late-Life Depression: The Rotterdam Study","volume":"61","author":"Tiemeier","year":"2004","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/00006842-200107000-00015","article-title":"Association of Depression and Diabetes Complications: A Meta-Analysis","volume":"63","author":"Groot","year":"2001","journal-title":"Psychosom. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1093\/aje\/kwi089","article-title":"Depressive Symptoms and Mortality among Persons with and without Diabetes","volume":"161","author":"Zhang","year":"2005","journal-title":"Am. J. Epidemiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Singh, J., Owusu Konadu, A.S., Li, Y., Shabaltiy, B., and Li, Y.L. (2026). Impact of PKC-MAPK Signaling on Cardiac Sympathetic Overactivation in Type-2 Diabetes Mellitus. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020723"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/S2213-8587(15)00135-7","article-title":"Constructs of Depression and Distress in Diabetes: Time for an Appraisal","volume":"3","author":"Snoek","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.62438\/tunismed.v104i01.5434","article-title":"Depressive comorbidity in type 2 Diabetes: Prevalence and associated factors","volume":"104","author":"Mhalla","year":"2026","journal-title":"Tunis. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1111\/dme.13611","article-title":"Prevalence and Correlates of Depressive Disorders in People with Type 2 Diabetes: Results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) Study, a Collaborative Study Carried out in 14 Countries","volume":"35","author":"Lloyd","year":"2018","journal-title":"Diabet. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Alajmani, D.S.A., Alkaabi, A.M., Alhosani, M.W., Folad, A.A., Abdouli, F.A., Carrick, F.R., and Abdulrahman, M. (2019). Prevalence of Undiagnosed Depression in Patients With Type 2 Diabetes. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00259"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.2337\/diacare.28.8.1904","article-title":"Depression and Diabetes: A Large Population-Based Study of Sociodemographic, Lifestyle, and Clinical Factors Associated with Depression in Type 1 and Type 2 Diabetes","volume":"28","author":"Engum","year":"2005","journal-title":"Diabetes Care"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1007\/s11606-008-0731-9","article-title":"Depression and Diabetes: A Potentially Lethal Combination","volume":"23","author":"Katon","year":"2008","journal-title":"J. Gen. Intern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1001\/archpsyc.59.7.605","article-title":"The Natural History of Late-Life Depression: A 6-Year Prospective Study in the Community","volume":"59","author":"Beekman","year":"2002","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1001\/archgenpsychiatry.2010.2","article-title":"Overweight, Obesity, and Depression: A Systematic Review and Meta-Analysis of Longitudinal Studies","volume":"67","author":"Luppino","year":"2010","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1017\/S0033291719000564","article-title":"Executive Dysfunction in Depression in Adolescence: The Role of Inflammation and Higher Body Mass","volume":"50","author":"Swistun","year":"2020","journal-title":"Psychol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ninla-Aesong, P., Puangsri, P., Kietdumrongwong, P., Jongkrijak, H., and Noipha, K. (2023). Being Overweight and Obese Increases Suicide Risk, the Severity of Depression, and the Inflammatory Response in Adolescents with Major Depressive Disorders. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1197775"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hallab, A. (2025). Health and Aging Brain Study (HABS-HD) Study Team. Mediating Effect of Pro-Inflammatory Cytokines in the Association between Depression, Anxiety, and Cardiometabolic Disorders in an Ethnically Diverse Community-Dwelling Middle-Aged and Older US Population. medRxiv.","DOI":"10.1101\/2025.04.14.25325836"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e47338","DOI":"10.1097\/MD.0000000000047338","article-title":"Unraveling the connection: Inflammatory markers and diabetes mellitus pathogenesis","volume":"105","author":"Obeagu","year":"2026","journal-title":"Medicine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0022-3956(82)90033-4","article-title":"Development and Validation of a Geriatric Depression Screening Scale: A Preliminary Report","volume":"17","author":"Yesavage","year":"1982","journal-title":"J. Psychiatr. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool for Mild Cognitive Impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"186106","DOI":"10.1155\/2013\/186106","article-title":"Montreal Cognitive Assessment Is Superior to Standardized Mini-Mental Status Exam in Detecting Mild Cognitive Impairment in the Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus","volume":"2013","author":"Alagiakrishnan","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1136\/jnnp.2005.085332","article-title":"Mild Cognitive Impairment (MCI) in Medical Practice: A Critical Review of the Concept and New Diagnostic Procedure. Report of the MCI Working Group of the European Consortium on Alzheimer\u2019s Disease","volume":"77","author":"Portet","year":"2006","journal-title":"J. Neurol. Neurosurg. Psychiatry"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6975\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:25:55Z","timestamp":1786353955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":49,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156975"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156975","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]}}}