{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:30:52Z","timestamp":1759883452476,"version":"build-2065373602"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovative Research Program of Xiangyang No.1 People's Hospital","award":["No.XYY2023QT20"],"award-info":[{"award-number":["No.XYY2023QT20"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>As an emerging insulin resistance marker, the relationship between estimated glucose disposal rate (eGDR) and frailty needs further exploration. This study examines the eGDR-frailty link, develops a machine learning predictive model to address this gap, and explores diabetes mellitus (DM) as a mediator, providing new insights for clinical intervention.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Using National Health and Nutrition Examination Survey (NHANES) 2005\u20132010 data, we analyzed glucose disposal and frailty associations. Feature selection used LASSO, and class imbalance was handled by SMOTEN. The resampled data were split 7:3 into a training set (n\u2009=\u200929,309) and a test set (n\u2009=\u200912,561).Ten machine learning models were built, with discrimination, calibration, and clinical utility evaluated to identify the optimal model. Confusion matrices visualized performance. Mediation analysis assessed DM\u2019s role in the eGDR-frailty relationship.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Among 26,282 participants, eGDR negatively correlated with frailty. Higher eGDR significantly reduced frailty risk in subgroups: women, age\u2009\u2264\u200960, normal\/high BMI, never\/current smokers, and alcohol users. LASSO selected 12 predictors. Across 10 models, CatBoost performed best on the test set (AUC\u2009=\u20090.970, accuracy\u2009=\u20090.920, F1\u2009=\u20090.918), with robust calibration and decision-curve net benefit. SHAP interpretation ranked eGDR among the most influential predictors: SHAP summary and dependence plots indicated that higher eGDR decreased the model\u2019s predicted probability of frailty. Confusion matrices validated classification accuracy. Mediation analysis showed DM partially mediated the eGDR-frailty relationship: indirect effect \u03b2=\u22120.003 (95% CI \u22120.003 to \u22120.002; P\u2009&lt;\u20090.001), mediation proportion\u2009=\u20098.71%.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This first NHANES-based study demonstrates a significant negative correlation between eGDR and frailty, confirming DM\u2019s partial mediating role. The developed machine learning models effectively support early frailty risk assessment and intervention.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0333388","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T17:35:29Z","timestamp":1759858529000},"page":"e0333388","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Estimated glucose disposal rate predicts frailty through diabetes: Evidence from machine learning and mediation models in NHANES"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9725-4415","authenticated-orcid":true,"given":"Wentao","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4784-430X","authenticated-orcid":true,"given":"Guoxin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongming","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"issue":"7","key":"pone.0333388.ref001","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1093\/gerona\/62.7.722","article-title":"Frailty in relation to the accumulation of deficits","volume":"62","author":"K Rockwood","year":"2007","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"6","key":"pone.0333388.ref002","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1111\/jgs.14135","article-title":"Prevalence and Incidence of Frailty in Community-Dwelling Older People: Beijing Longitudinal Study of Aging II","volume":"64","author":"Z Zheng","year":"2016","journal-title":"J Am Geriatr Soc"},{"issue":"1","key":"pone.0333388.ref003","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1186\/s12916-022-02596-7","article-title":"Relationship of body mass index with frailty and all-cause mortality among middle-aged and older adults","volume":"20","author":"K Jayanama","year":"2022","journal-title":"BMC Med"},{"issue":"4","key":"pone.0333388.ref004","doi-asserted-by":"crossref","first-page":"327","DOI":"10.14283\/jfa.2021.14","article-title":"Frailty in Young and Middle-Aged Adults: An Integrative Review","volume":"10","author":"C Loecker","year":"2021","journal-title":"The Journal of Frailty & Aging"},{"issue":"1","key":"pone.0333388.ref005","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1186\/s12877-021-02344-1","article-title":"Bidirectional relationship between subjective age and frailty: a prospective cohort study","volume":"21","author":"Y Li","year":"2021","journal-title":"BMC Geriatr"},{"issue":"4","key":"pone.0333388.ref006","doi-asserted-by":"crossref","first-page":"252","DOI":"10.5582\/bst.2023.01204","article-title":"Healthy aging, early screening, and interventions for frailty in the elderly","volume":"17","author":"Y Deng","year":"2023","journal-title":"Biosci Trends"},{"issue":"8","key":"pone.0333388.ref007","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1111\/j.1532-5415.2012.04074.x","article-title":"Comparison of frailty indicators based on clinical phenotype and the multiple deficit approach in predicting mortality and physical limitation","volume":"60","author":"J Woo","year":"2012","journal-title":"J Am Geriatr Soc"},{"issue":"1","key":"pone.0333388.ref008","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.gerinurse.2020.08.017","article-title":"Comparison of 6 frailty screening tools in diagnostic properties among Chinese community-dwelling older people","volume":"42","author":"H Si","year":"2021","journal-title":"Geriatric Nursing"},{"issue":"1","key":"pone.0333388.ref009","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1186\/s12933-024-02256-5","article-title":"Insulin resistance assessed by estimated glucose disposal rate and risk of incident cardiovascular diseases among individuals without diabetes: findings from a nationwide, population based, prospective cohort study","volume":"23","author":"Z Zhang","year":"2024","journal-title":"Cardiovasc Diabetol"},{"issue":"1","key":"pone.0333388.ref010","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1186\/s12916-024-03582-x","article-title":"Estimated glucose disposal rate for predicting cardiovascular events and mortality in patients with non-diabetic chronic kidney disease: a prospective cohort study","volume":"22","author":"J Peng","year":"2024","journal-title":"BMC Med"},{"issue":"5","key":"pone.0333388.ref011","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1093\/ageing\/afx023","article-title":"Metabolic syndrome and insulin resistance are associated with frailty in older adults: a prospective cohort study","volume":"46","author":"RF P\u00e9rez-Tasigchana","year":"2017","journal-title":"Age Ageing"},{"issue":"4","key":"pone.0333388.ref012","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1002\/jcsm.13516","article-title":"Long-term insulin resistance is associated with frailty, frailty progression, and cardiovascular disease","volume":"15","author":"Z Ke","year":"2024","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"5","key":"pone.0333388.ref013","doi-asserted-by":"crossref","first-page":"641","DOI":"10.4093\/dmj.2021.0220","article-title":"Assessment of Insulin Secretion and Insulin Resistance in Human","volume":"45","author":"SY Park","year":"2021","journal-title":"Diabetes Metab J"},{"issue":"1","key":"pone.0333388.ref014","doi-asserted-by":"crossref","DOI":"10.1152\/ajpendo.00645.2007","article-title":"Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage","volume":"294","author":"R Muniyappa","year":"2008","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"4","key":"pone.0333388.ref015","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1002\/jcsm.13516","article-title":"Long-term insulin resistance is associated with frailty, frailty progression, and cardiovascular disease","volume":"15","author":"Z Ke","year":"2024","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"1","key":"pone.0333388.ref016","article-title":"Association between HOMA-IR and Frailty among U.S. Middle-aged and Elderly Population","volume":"9","author":"P-S Peng","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0333388.ref017","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s12933-025-02650-7","article-title":"Associations of estimated glucose disposal rate with frailty progression: results from two prospective cohorts","volume":"24","author":"Z Wang","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"pone.0333388.ref018","doi-asserted-by":"crossref","first-page":"105764","DOI":"10.1016\/j.archger.2025.105764","article-title":"Associations of insulin resistance estimated by glucose disposal rate with frailty progression","volume":"131","author":"J Sun","year":"2025","journal-title":"Arch Gerontol Geriatr"},{"issue":"12","key":"pone.0333388.ref019","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.2105\/AJPH.2021.306517","article-title":"The National Health and Nutrition Examination Survey (NHANES), 2021\u20132022: Adapting Data Collection in a COVID-19 Environment","volume":"111","author":"R Paulose-Ram","year":"2021","journal-title":"Am J Public Health"},{"key":"pone.0333388.ref020","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1471-2318-8-24","article-title":"A standard procedure for creating a frailty index","volume":"8","author":"SD Searle","year":"2008","journal-title":"BMC Geriatr"},{"key":"pone.0333388.ref021","doi-asserted-by":"crossref","first-page":"107904","DOI":"10.1016\/j.maturitas.2023.107904","article-title":"Age at first birth is associated with the likelihood of frailty in middle-aged and older women: A population-based analysis from NHANES 1999-2018","volume":"181","author":"H-J Guo","year":"2024","journal-title":"Maturitas"},{"key":"pone.0333388.ref022","doi-asserted-by":"crossref","first-page":"1403409","DOI":"10.3389\/fpubh.2024.1403409","article-title":"Association between added sugars and frailty in U.S. adults: a cross-sectional study from the National Health and Nutrition Examination Survey 2007-2018","volume":"12","author":"J Ji","year":"2024","journal-title":"Front Public Health"},{"issue":"4","key":"pone.0333388.ref023","doi-asserted-by":"crossref","first-page":"626","DOI":"10.2337\/diabetes.49.4.626","article-title":"Can clinical factors estimate insulin resistance in type 1 diabetes?","volume":"49","author":"KV Williams","year":"2000","journal-title":"Diabetes"},{"key":"pone.0333388.ref024","doi-asserted-by":"crossref","first-page":"1439326","DOI":"10.3389\/fendo.2024.1439326","article-title":"Cross-sectional comparison of the association between three different insulin resistance surrogates and frailty: NHANES 1999-2018","volume":"15","author":"T Lai","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"pone.0333388.ref025","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.puhe.2022.10.021","article-title":"Trends and disparities in diabetes and prediabetes among adults in the United States, 1999-2018","volume":"214","author":"J Liu","year":"2023","journal-title":"Public Health"},{"issue":"2","key":"pone.0333388.ref026","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.cdtm.2020.11.003","article-title":"National trends in insulin resistance and \u03b2\u2010cell dysfunction among adults with prediabetes: NHANES 2001\u20132016","volume":"7","author":"H Zhang","year":"2021","journal-title":"Chronic Diseases and Translational Medicine"},{"key":"pone.0333388.ref027","doi-asserted-by":"crossref","first-page":"1398265","DOI":"10.3389\/fendo.2024.1398265","article-title":"Associations between estimated glucose disposal rate and arterial stiffness and mortality among US adults with non-alcoholic fatty liver disease","volume":"15","author":"J Song","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"pone.0333388.ref028","doi-asserted-by":"crossref","first-page":"1483468","DOI":"10.3389\/fendo.2024.1483468","article-title":"Association between various insulin resistance indices and cardiovascular disease in middle-aged and elderly individuals: evidence from two prospectives nationwide cohort surveys","volume":"15","author":"Y Li","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"pone.0333388.ref029","doi-asserted-by":"crossref","first-page":"111317","DOI":"10.1016\/j.exger.2021.111317","article-title":"Frailty is associated with chronic inflammation and pro-inflammatory monocyte subpopulations","volume":"149","author":"M Cybularz","year":"2021","journal-title":"Exp Gerontol"},{"key":"pone.0333388.ref030","first-page":"102","article-title":"Effects of ageing on insulin secretion and action","volume":"60","author":"N M\u00f8ller","year":"2003","journal-title":"Horm Res"},{"issue":"1","key":"pone.0333388.ref031","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4093\/dmj.2023.0110","article-title":"Primordial Drivers of Diabetes Heart Disease: Comprehensive Insights into Insulin Resistance","volume":"48","author":"Y Fan","year":"2024","journal-title":"Diabetes Metab J"},{"issue":"6","key":"pone.0333388.ref032","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s12603-022-1793-9","article-title":"Biomarkers of Age-Related Frailty and Frailty Related to Diseases: An Exploratory, Cross-Sectional Analysis from the MAPT Study","volume":"26","author":"D Angioni","year":"2022","journal-title":"J Nutr Health Aging"},{"issue":"1","key":"pone.0333388.ref033","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/ggi.13571","article-title":"Associations of social frailty with loss of muscle mass and muscle weakness among community-dwelling older adults","volume":"19","author":"H Makizako","year":"2019","journal-title":"Geriatr Gerontol Int"},{"key":"pone.0333388.ref034","doi-asserted-by":"crossref","first-page":"101264","DOI":"10.1016\/j.eclinm.2021.101264","article-title":"Association between sarcopenia and cardiovascular disease among middle-aged and older adults: Findings from the China health and retirement longitudinal study","volume":"44","author":"K Gao","year":"2022","journal-title":"EClinicalMedicine"},{"issue":"8","key":"pone.0333388.ref035","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1111\/j.1532-5415.2012.04054.x","article-title":"Prevalence of frailty in community-dwelling older persons: a systematic review","volume":"60","author":"RM Collard","year":"2012","journal-title":"J Am Geriatr Soc"},{"issue":"12","key":"pone.0333388.ref036","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.3390\/nu13124291","article-title":"Associated Factors of Sarcopenia in Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis","volume":"13","author":"Q Gao","year":"2021","journal-title":"Nutrients"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0333388","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T17:35:55Z","timestamp":1759858555000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0333388"}},"subtitle":[],"editor":[{"given":"Yee Gary","family":"Ang","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,7]]},"references-count":36,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0333388","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,7]]}}}