{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:15:13Z","timestamp":1789985713231,"version":"4.0.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The neutrophil-lymphocyte ratio (NLR) is a hematological marker to assess systemic inflammation and immune status. The relationship between NLR and the risk of mortality in individuals with diabetes mellitus or pre-diabetes mellitus who have comorbid symptoms of obstructive sleep apnea is unknown. Our study aims to evaluate the association between NLR and all-cause and cardiovascular mortality in this population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Our research enrolled 5432 patients from the National Health and Nutrition Examination Surveys (2005-2008 and 2015-2018) diagnosed with diabetes or prediabetes combined with symptoms of OSA. Mortality outcomes were ascertained by linkage to the National Death Index (NDI) records for December 31, 2019. The association between NLR and mortality was tested using multivariate Cox regression models. The non-linear relationship was analyzed based on restricted cubic spline curves (RCS). Kaplan-Meier (K-M) survival analysis and time-dependent subject operating characteristic curve (ROC) analysis were performed to assess the predictive value of NLR on patient survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In a median follow-up period of 52 months, study participants experienced 632 deaths from all causes and 143 deaths due to cardiovascular disease. According to Cox regression analysis, the fourth quartile was associated with higher all-cause mortality (HR=1.76, 95% CI 1.25-2.49) and cardiovascular mortality (HR=3.08, 95% CI 1.54-6.18) compared with the first quartile under the fully adjusted model. Meanwhile, K-M survival curves showed that all-cause and cardiovascular mortality increased with increasing NLR levels, with the highest mortality in the fourth quartile group. In addition, the areas under the curve (AUC) of the 3, 5and 10year survival were 0.67, 0.63, and 0.74 for all-cause mortality, respectively. Meanwhile, the AUC values \u200b\u200bfor cardiovascular mortality were 0.73, 0.56, and 0.69.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>For individuals with diabetes and OSA symptoms, elevated NLR can serve as a prognostic indicator for all-cause and cardiovascular mortality.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1512621","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T04:10:17Z","timestamp":1745295017000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Association between neutrophil-lymphocyte ratio and all-cause and cardiovascular mortality in patients with diabetes or prediabetes with comorbid obstructive sleep apnea symptoms: evidence from NHANES 2005-2008 and 2015-2018"],"prefix":"10.3389","volume":"16","author":[{"given":"Jin-Mao","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2020.02.036","article-title":"Update on persistent excessive daytime sleepiness in OSA","volume":"158","author":"Javaheri","year":"2020","journal-title":"Chest"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.3514","article-title":"Diagnosis and management of obstructive sleep apnea: A review","volume":"323","author":"Gottlieb","year":"2020","journal-title":"JAMA"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kws342","article-title":"Increased prevalence of sleep-disordered breathing in adults","volume":"177","author":"Peppard","year":"2013","journal-title":"Am J Epidemiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-022-01181-w","article-title":"Obstructive sleep apnea and hypertension: updates to a critical relationship","volume":"24","author":"Brown","year":"2022","journal-title":"Curr Hypertens Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/diseases9040088","article-title":"Association and risk factors for obstructive sleep apnea and cardiovascular diseases: A systematic review","volume":"9","author":"Mitra","year":"2021","journal-title":"Diseases"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2017.05.009","article-title":"Obstructive sleep apnea and diabetes: A state of the art review","volume":"152","author":"Reutrakul","year":"2017","journal-title":"Chest"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res Clin Pract"},{"key":"B8","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1056\/NEJMoa012512","article-title":"Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin","volume":"346","author":"Knowler","year":"2002","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/pl00002944","article-title":"Vascular disease prevalence in diabetic patients in China: standardised comparison with the 14 centres in the WHO Multinational Study of Vascular Disease in Diabetes","author":"Chi","year":"2001","journal-title":"Diabetologia"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0393-2","article-title":"Do known risk factors explain the higher coronary heart disease mortality in South Asian compared with European men? Prospective follow-up of the Southall and Brent studies, UK","volume":"49","author":"Forouhi","year":"2006","journal-title":"Diabetologia"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjr.0000368191.86614.5a","article-title":"The global burden of diabetes and its complications: an emerging pandemic","author":"van Dieren","year":"2010","journal-title":"Eur J Cardiovasc Prev Rehabil"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e011295","DOI":"10.1161\/JAHA.118.011295","article-title":"Diabetes mellitus-related all-cause and cardiovascular mortality in a national cohort of adults","volume":"8","author":"Raghavan","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.3.702","article-title":"Diabetes and sleep disturbances: findings from the Sleep Heart Health Study","volume":"26","author":"Resnick","year":"2003","journal-title":"Diabetes Care"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-1776","article-title":"Obstructive sleep apnea among obese patients with type 2 diabetes","volume":"32","author":"Foster","year":"2009","journal-title":"Diabetes Care"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2014.08.023","article-title":"Obstructive sleep apnea and type 2 diabetes in older adults","volume":"31","author":"Moon","year":"2015","journal-title":"Clinics Geriatric Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1186\/s12916-020-01817-1","article-title":"Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies","volume":"18","author":"Cupp","year":"2020","journal-title":"BMC Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2019.10.023","article-title":"Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: A meta-analysis","volume":"38","author":"Huang","year":"2020","journal-title":"Am J Emerg Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2021.11.083","article-title":"Is the neutrophil-to-lymphocyte ratio an exceptional indicator for metabolic syndrome disease and outcomes","volume":"28","author":"Hashemi Moghanjoughi","year":"2022","journal-title":"Endocr Pract"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2022.04.092","article-title":"Neutrophil\/lymphocyte, platelet\/lymphocyte and monocyte\/lymphocyte ratios in patients with affective disorders","volume":"309","author":"Wei","year":"2022","journal-title":"J Affect Disord"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2020.577398","article-title":"The neutrophil-to-lymphocyte ratio in Alzheimer\u2019s disease: Current understanding and potential applications","volume":"349","author":"Sayed","year":"2020","journal-title":"J Neuroimmunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-3116","article-title":"Type 2 diabetes mellitus and efficacy outcomes from immune checkpoint blockade in patients with cancer","volume":"29","author":"Cortellini","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/3117396","article-title":"The association between neutrophil-to-lymphocyte ratio and glycemic control in type 2 diabetes mellitus: A systematic review and meta-analysis","volume":"2023","author":"Adane","year":"2023","journal-title":"J Diabetes Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12933-023-01998-y","article-title":"The neutrophil\u2013lymphocyte ratio as a risk factor for all-cause and cardiovascular mortality among individuals with diabetes: evidence from the NHANES 2003\u20132016","volume":"22","author":"Dong","year":"2023","journal-title":"Cardiovasc Diabetol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/S2213-8587(18)30316-4","article-title":"Novel subgroups of patients with adult-onset diabetes in Chinese and US populations","volume":"7","author":"Zou","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12933-024-02172-8","article-title":"The prognostic value of the stress hyperglycemia ratio for all-cause and cardiovascular mortality in patients with diabetes or prediabetes: insights from NHANES 2005-2018","volume":"23","author":"Ding","year":"2024","journal-title":"Cardiovasc Diabetol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleh.2022.05.005","article-title":"Antimony and sleep health outcomes: NHANES 2009-2016","volume":"8","author":"Cavallino","year":"2022","journal-title":"Sleep Health"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.795391","article-title":"Association of serum vitamin C with NAFLD and MAFLD among adults in the United States","volume":"8","author":"Zq","year":"2022","journal-title":"Front Nutr"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.aohep.2020.03.006","article-title":"Blood lead level is associated with advanced liver fibrosis in patients with non-alcoholic fatty liver disease: A nationwide survey (NHANES 2011\u20132016)","volume":"19","author":"Reja","year":"2020","journal-title":"Ann Hepatol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3109\/0886022X.2012.668741","article-title":"Neutrophil-to-lymphocyte ratio as a predictor of worsening renal function in diabetic patients (3-year follow-up study)","volume":"34","author":"Azab","year":"2012","journal-title":"Ren Fail"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030459","article-title":"Obstructive sleep apnea and inflammation: proof of concept based on two illustrative cytokines","volume":"20","author":"Kheirandish-Gozal","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-011-9340-1","article-title":"Cardiovascular consequences of sleep apnea","volume":"190","author":"Golbidi","year":"2012","journal-title":"Lung"},{"key":"B32","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s11154-014-9304-x","article-title":"Inflammation in sleep apnea: an update","volume":"16","author":"Unnikrishnan","year":"2015","journal-title":"Rev Endocr Metab Disord"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2023.05.094","article-title":"Dapagliflozin restores diabetes-associated decline in vasculogenic capacity of endothelial progenitor cells via activating AMPK-mediated inhibition of inflammation and oxidative stress","volume":"671","author":"Luo","year":"2023","journal-title":"Biochem Biophys Res Commun"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073636","article-title":"Neutrophil to lymphocyte ratio: an emerging marker of the relationships between the immune system and diseases","volume":"23","author":"Buonacera","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B35","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1186\/s12872-023-03316-6","article-title":"Association between neutrophil percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and long-term mortality in community-dwelling adults with heart failure: evidence from US NHANES 2005-2016","volume":"23","author":"Wu","year":"2023","journal-title":"BMC Cardiovasc Disord"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(13)70039-0","article-title":"Obstructive sleep apnoea and type 2 diabetes mellitus: a bidirectional association","volume":"1","author":"Aurora","year":"2013","journal-title":"Lancet Respir Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2147\/NSS.S90835","article-title":"Obstructive sleep apnea as a risk factor for type 2 diabetes mellitus","volume":"7","author":"Rajan","year":"2015","journal-title":"Nat Sci Sleep"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.556746","article-title":"Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome","volume":"112","author":"Ryan","year":"2005","journal-title":"Circulation"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.212217","article-title":"The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature","volume":"106","author":"Yan","year":"2010","journal-title":"Circ Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002615","article-title":"Elevated proinflammatory cytokine production by a skewed T cell compartment requires monocytes and promotes inflammation in type 2 diabetes","volume":"186","author":"Jagannathan-Bogdan","year":"2011","journal-title":"J Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1186\/s12888-023-05286-7","article-title":"Analysis of the relationship between sleep-related disorder and systemic immune-inflammation index in the US population","volume":"23","author":"Kadier","year":"2023","journal-title":"BMC Psychiatry"},{"key":"B42","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s12902-024-01592-7","article-title":"Association of neutrophil-lymphocyte ratio with all-cause and cardiovascular mortality in US adults with diabetes and prediabetes: a prospective cohort study","volume":"24","author":"Chen","year":"2024","journal-title":"BMC Endocr Disord"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-017-8648-x","article-title":"Sexual dimorphism in innate immunity","volume":"56","author":"Jaillon","year":"2019","journal-title":"Clin Rev Allergy Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2019.04.016","article-title":"Experienced discrimination and racial differences in leukocyte gene expression","volume":"106","author":"Thames","year":"2019","journal-title":"Psychoneuroendocrinology"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810891","article-title":"Immuno-mediated inflammation in hypertensive patients with 1-h post-load hyperglycemia","volume":"23","author":"Perticone","year":"2022","journal-title":"IJMS"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2020.02.47","article-title":"Cardiovascular risk of smoking and benefits of smoking cessation","volume":"12","author":"Gallucci","year":"2020","journal-title":"J Thorac Dis"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1512621\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T04:10:18Z","timestamp":1745295018000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1512621\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,22]]},"references-count":46,"alternative-id":["10.3389\/fendo.2025.1512621"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1512621","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,22]]},"article-number":"1512621"}}