{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:29:21Z","timestamp":1785403761579,"version":"3.56.0"},"reference-count":44,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008055","name":"Fundaci\u00f3n Eugenio Rodr\u00edguez Pascual","doi-asserted-by":"crossref","award":["ERP-2021"],"award-info":[{"award-number":["ERP-2021"]}],"id":[{"id":"10.13039\/100008055","id-type":"DOI","asserted-by":"crossref"}]},{"award":["ERP-2021"],"award-info":[{"award-number":["ERP-2021"]}],"id":[{"id":"https:\/\/ror.org\/03p40sz62","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Operational Programme of the European Regional Development Fund","award":["C-CTS-094-UGR23"],"award-info":[{"award-number":["C-CTS-094-UGR23"]}]},{"name":"International Scholarship \u201cBOLASHAQ\u201d Program, Government of Kazakhstan","award":["7895"],"award-info":[{"award-number":["7895"]}]},{"name":"International Scholarship \u201cBOLASHAQ\u201d Program, Government of Kazakhstan","award":["8534"],"award-info":[{"award-number":["8534"]}]},{"name":"Centro de Ense\u00f1anza T\u00e9cnica Industrial"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Type 2 diabetes mellitus (T2DM) is a major global health challenge due to its high prevalence and association with chronic complications, highlighting the need for reliable predictive tools to support clinical decision-making. Methods: This study proposes a two-stage hierarchical prediction system based on a Random Forest (RF) classifier. In Stage 1, the model performs multiclass classification into healthy (H), T2DM without complications (D), and T2DM with complications (C). In Stage 2, patients classified as C are further stratified into microvascular or macrovascular complications. The dataset included 31 biochemical, molecular, inflammatory, and oxidative stress variables from Mexican and Spanish cohorts. Feature selection was performed using Pearson correlation, and feature relevance was further assessed using RF importance measures. Model training used stratified cross-validation, with additional evaluation on a hold-out set to approximate real-world performance. Results: The optimized RF achieved an accuracy of 92% and a macro F1-score of 0.92, outperforming baseline models, with an AUC-ROC of 0.89 for complication prediction. Key predictive features included IL-18, miR-126, duration of T2DM, HbA1c, and IL-10. Conclusions: The novelty of this study lies in integrating heterogeneous biomarkers within a hierarchical predictive framework, rather than in the machine learning algorithm itself. This multimodal approach, combined with interpretable machine learning techniques, is designed to deliver clinically meaningful insights for patient stratification and personalized management in T2DM.<\/jats:p>","DOI":"10.3390\/diagnostics16132040","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:01:17Z","timestamp":1782813677000},"page":"2040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Machine Learning Integration of Clinical and Molecular Biomarkers to Predict Vascular Complications in Type 2 Diabetes"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0884-7893","authenticated-orcid":false,"given":"Gerardo","family":"Garc\u00eda-Gil","sequence":"first","affiliation":[{"name":"Centro de Ense\u00f1anza T\u00e9cnica Industrial, Subdirecci\u00f3n de Investigaci\u00f3n y Extensi\u00f3n, Laboratorio de Biom\u00e9dica\/IDS, Guadalajara 44638, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4598-0649","authenticated-orcid":false,"given":"V\u00edctor Manuel","family":"Medina-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Laboratorio de Sistemas Aut\u00f3nomos para Dise\u00f1o Biotecnol\u00f3gico, Maestr\u00eda en Ciencias en Bioingenier\u00eda y C\u00f3mputo Inteligente, Centro Universitario de Ciencias Exactas e Ingenier\u00edas, Universidad de Guadalajara, Guadalajara 44430, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Becerra-Contreras","sequence":"additional","affiliation":[{"name":"Centro Universitario de Ciencias Biol\u00f3gicas y Agropecuarias, Universidad de Guadalajara, Zapopan 44600, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5791-612X","authenticated-orcid":false,"given":"Jos\u00e9 Alfonso","family":"Cruz-Ramos","sequence":"additional","affiliation":[{"name":"Instituto de Patolog\u00eda Infecciosa y Experimental Francisco Ruiz S\u00e1nchez, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9743-3739","authenticated-orcid":false,"given":"Esteban","family":"Gonz\u00e1lez-D\u00edaz","sequence":"additional","affiliation":[{"name":"Instituto de Patolog\u00eda Infecciosa y Experimental Francisco Ruiz S\u00e1nchez, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor Ra\u00fal","family":"P\u00e9rez-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Instituto de Patolog\u00eda Infecciosa y Experimental Francisco Ruiz S\u00e1nchez, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4243-497X","authenticated-orcid":false,"given":"Kevin Javier","family":"Arellano-Arteaga","sequence":"additional","affiliation":[{"name":"Servicio de Medicina Interna, Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca, Departamento de Cl\u00ednicas M\u00e9dicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0706-6614","authenticated-orcid":false,"given":"Arailym","family":"Yessenbekova","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Biomedicine and Neuroscience, Farabi University, Farabi Av. 71, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5204-4748","authenticated-orcid":false,"given":"Botagoz","family":"Ussipbek","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Biomedicine and Neuroscience, Farabi University, Farabi Av. 71, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurzhanyat","family":"Ablaikhanova","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Biomedicine and Neuroscience, Farabi University, Farabi Av. 71, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9034-7600","authenticated-orcid":false,"given":"Iryna","family":"Rusanova","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular I, Facultad de Ciencias, Universidad de Granada, 18016 Granada, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica, Parque Tecnol\u00f3gico de Ciencias de la Salud, Universidad de Granada, 18016 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria (IBS Granada), Hospital Universitario San Cecilio, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-8764","authenticated-orcid":false,"given":"Gabriela del C.","family":"L\u00f3pez-Armas","sequence":"additional","affiliation":[{"name":"Centro de Ense\u00f1anza T\u00e9cnica Industrial, Subdirecci\u00f3n de Investigaci\u00f3n y Extensi\u00f3n, Laboratorio de Biom\u00e9dica\/IDS, Guadalajara 44638, Mexico"},{"name":"Direcci\u00f3n del Laboratorio Estatal de Salud P\u00fablica, Secretar\u00eda de Salud Jalisco, Zapopan 45170, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"Cho","year":"2018","journal-title":"Diabetes Res. 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