{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T08:51:24Z","timestamp":1791881484731,"version":"4.3.4"},"reference-count":174,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2D) represents over 90% of diabetes cases globally, posing a growing public health crisis with an estimated 783 million adults projected to be affected by 2045. This condition arises from a complex interplay of insulin resistance, progressive pancreatic \u03b2-cell dysfunction, and chronic low-grade inflammation, strongly influenced by genetic predisposition, obesity, sedentary lifestyle, and poor dietary habits. While genome-wide association studies (GWAS) have identified key susceptibility loci, including TCF7L2, PPARG, and KCNJ11, these varian0ts explain only ~10% of T2D heritability, underscoring the critical role of gene\u2013environment interactions. This review synthesizes current evidence on the genetic, nutrigenomic, and epigenetic mechanisms underlying T2D pathogenesis and progression. We examine how dietary components, such as flavonoids, terpenoids, alkaloids, and bioactive compounds from natural products, modulate gene expression via transcription factors and influence insulin sensitivity, oxidative stress, and inflammation. Furthermore, we explore the emerging role of epigenetic modifications, including DNA methylation, histone acetylation, and chromatin remodeling, in mediating the lasting effects of hyperglycemia and environmental factors on T2D risk. The potential of epigenetic biomarkers for early diagnosis, patient stratification, and personalized therapy is discussed. Finally, we highlight how next-generation sequencing and artificial intelligence, particularly machine learning and deep learning models, are advancing multi-omics data integration, enabling improved T2D subtype classification, prognosis prediction, and the development of precision nutrition and pharmacoepigenetic strategies.<\/jats:p>","DOI":"10.3390\/nu18193206","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:46:29Z","timestamp":1790599589000},"page":"3206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Genes to Diets: A Critical Review of Genetic, Nutrigenomic and Epigenetic Mechanisms in Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3184-169X","authenticated-orcid":false,"given":"Rafael G.","family":"Ara\u00fajo","sequence":"first","affiliation":[{"name":"Center for Research in Genetics and Genomics (CIGEN), The Autonomous University of Coahuila, Saltillo 25000, Coahuila, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Ortiz-Cruz","sequence":"additional","affiliation":[{"name":"Center for Research in Genetics and Genomics (CIGEN), The Autonomous University of Coahuila, Saltillo 25000, Coahuila, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2416-4678","authenticated-orcid":false,"given":"Sunday Sedodo","family":"Nupo","sequence":"additional","affiliation":[{"name":"Center for Research in Genetics and Genomics (CIGEN), The Autonomous University of Coahuila, Saltillo 25000, Coahuila, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulianna","family":"Cordero","sequence":"additional","affiliation":[{"name":"Center for Research in Genetics and Genomics (CIGEN), The Autonomous University of Coahuila, Saltillo 25000, Coahuila, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauro","family":"Cortes-Hernandez","sequence":"additional","affiliation":[{"name":"Center for Research in Genetics and Genomics (CIGEN), The Autonomous University of Coahuila, Saltillo 25000, Coahuila, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1705-485X","authenticated-orcid":false,"given":"Sandra Luc\u00eda","family":"Teniente","sequence":"additional","affiliation":[{"name":"Center for Research in Genetics and Genomics (CIGEN), The Autonomous University of Coahuila, Saltillo 25000, Coahuila, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00508-022-02122-y","article-title":"Diabetes Mellitus\u2014Definition, Klassifikation, Diagnose, Screening und Pr\u00e4vention (Update 2023)","volume":"135","author":"Harreiter","year":"2023","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.7748\/ns.2021.e11709","article-title":"Diabetes Mellitus: An Overview of the Types, Symptoms, Complications and Management","volume":"37","author":"Cloete","year":"2022","journal-title":"Nurs. Stand."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.2174\/138955751514151006154616","article-title":"Treatment and Diagnosis of Diabetes Mellitus and Its Complication: Advanced Approaches","volume":"15","author":"Sen","year":"2015","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2100275","DOI":"10.1002\/advs.202100275","article-title":"Emerging Targets in Type 2 Diabetes and Diabetic Complications","volume":"8","author":"Demir","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, Regional and Country-Level Diabetes Prevalence Estimates for 2021 and Projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1161\/ATVBAHA.116.307302","article-title":"Impact of Diabetes Mellitus","volume":"36","author":"Kanter","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1055\/a-1018-9078","article-title":"Definition, Classification and Diagnosis of Diabetes Mellitus","volume":"127","author":"Petersmann","year":"2019","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2011). Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 34, S62\u2013S69.","DOI":"10.2337\/dc11-S062"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2018). 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes\u20142018. Diabetes Care, 41, S13\u2013S27.","DOI":"10.2337\/dc18-S002"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"717","DOI":"10.2174\/187153031906190724104004","article-title":"Current Genetic and Epigenetic Insights into Type 2 Diabetes Mellitus","volume":"19","author":"Alam","year":"2019","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Majety, P., Lozada Orquera, F.A., Edem, D., and Hamdy, O. (2023). Pharmacological Approaches to the Prevention of Type 2 Diabetes Mellitus. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1118848"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s11892-019-1173-y","article-title":"The Genetic Epidemiology of Type 2 Diabetes: Opportunities for Health Translation","volume":"19","author":"Meigs","year":"2019","journal-title":"Curr. Diabetes Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/jdi.13970","article-title":"Progress in Genetics of Type 2 Diabetes and Diabetic Complications","volume":"14","author":"Shojima","year":"2023","journal-title":"J. Diabetes Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s11154-023-09804-6","article-title":"Genetics and Epigenetics in the Obesity Phenotyping Scenario","volume":"24","author":"Trang","year":"2023","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/joim.13049","article-title":"Epigenetic Regulation of Insulin Action and Secretion\u2014Role in the Pathogenesis of Type 2 Diabetes","volume":"288","author":"Ling","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e220","DOI":"10.1038\/emm.2016.7","article-title":"Recent Progress in Genetic and Epigenetic Research on Type 2 Diabetes","volume":"48","author":"Kwak","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/s41591-022-01790-7","article-title":"Heterogeneity in Phenotype, Disease Progression and Drug Response in Type 2 Diabetes","volume":"28","author":"Nair","year":"2022","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K.B., Ostolaza, H., and Mart\u00edn, C. (2020). Pathophysiology of Type 2 Diabetes Mellitus. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176275"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Dilworth, L., Facey, A., and Omoruyi, F. (2021). Diabetes Mellitus and Its Metabolic Complications: The Role of Adipose Tissues. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147644"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/S0140-6736(17)30058-2","article-title":"Type 2 Diabetes","volume":"389","author":"Chatterjee","year":"2017","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lewis, S.T., Greenway, F., Tucker, T.R., Alexander, M., Jackson, L.K., Hepford, S.A., Loveridge, B., and Lakey, J.R.T. (2023). A Receptor Story: Insulin Resistance Pathophysiology and Physiologic Insulin Resensitization\u2019s Role as a Treatment Modality. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310927"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/S0140-6736(05)61032-X","article-title":"Type 2 Diabetes: Principles of Pathogenesis and Therapy","volume":"365","author":"Stumvoll","year":"2005","journal-title":"Lancet"},{"key":"ref_23","first-page":"107","article-title":"Epidemiology of Type 2 Diabetes\u2014Global Burden of Disease and Forecasted Trends","volume":"10","author":"Hashim","year":"2020","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e06339","DOI":"10.1016\/j.heliyon.2021.e06339","article-title":"Prevalence and Associated Factors of Overweight\/Obesity among Type 2 Diabetic Outpatients in Southwest Ethiopia","volume":"7","author":"Abdissa","year":"2021","journal-title":"Heliyon"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chandrasekaran, P., and Weiskirchen, R. (2024). The Role of Obesity in Type 2 Diabetes Mellitus\u2014An Overview. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031882"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e039258","DOI":"10.1136\/bmjopen-2020-039258","article-title":"Prevalence and Factors Associated with Overweight and Obesity among Participants with Type 2 Diabetes Mellitus in Uganda\u2014A Descriptive Retrospective Study","volume":"10","author":"Tino","year":"2020","journal-title":"BMJ Open"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1001\/jamainternmed.2019.5942","article-title":"Ultraprocessed Food Consumption and Risk of Type 2 Diabetes among Participants of the NutriNet-Sant\u00e9 Prospective Cohort","volume":"180","author":"Srour","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"944","DOI":"10.2337\/dc22-1954","article-title":"Association and Interaction of Genetics and Area-Level Socioeconomic Factors on the Prevalence of Type 2 Diabetes and Obesity","volume":"46","author":"Cromer","year":"2023","journal-title":"Diabetes Care"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.2337\/dc16-2053","article-title":"Psychosocial Care for People with Diabetes: A Position Statement of the American Diabetes Association","volume":"39","author":"Gonzalez","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1210\/clinem\/dgae488","article-title":"The Association between Obesity and Polycystic Ovary Syndrome: An Epidemiologic Study of Observational Data","volume":"109","author":"Amiri","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yan, Y., Xu, M., Wu, M., Wang, X., Li, F., Zhang, J., You, L., Pan, X., Feng, W., and Wu, J. (2022). Obesity Is Associated with Subclinical Hypothyroidism in the Presence of Thyroid Autoantibodies: A Cross-Sectional Study. BMC Endocr. Disord., 22.","DOI":"10.1186\/s12902-022-00981-0"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Carli, M., Kolachalam, S., Longoni, B., Pintaudi, A., Baldini, M., Aringhieri, S., Fasciani, I., Annibale, P., Maggio, R., and Scarselli, M. (2021). Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences. Pharmaceuticals, 14.","DOI":"10.3390\/ph14030238"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1056\/NEJMoa010492","article-title":"Diet, Lifestyle, and the Risk of Type 2 Diabetes Mellitus in Women","volume":"345","author":"Hu","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"543","DOI":"10.7326\/0003-4819-159-8-201310150-00007","article-title":"Lifestyle Interventions for Patients with and at Risk for Type 2 Diabetes: A Systematic Review and Meta-Analysis","volume":"159","author":"Schellenberg","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.mcna.2004.04.013","article-title":"Pathogenesis of Type 2 Diabetes Mellitus","volume":"88","author":"DeFronzo","year":"2004","journal-title":"Med. Clin. N. Am."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S97","DOI":"10.2337\/diabetes.54.suppl_2.S97","article-title":"Mechanisms of Pancreatic Beta-Cell Death in Type 1 and Type 2 Diabetes: Many Differences, Few Similarities","volume":"54","author":"Cnop","year":"2005","journal-title":"Diabetes"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e101","DOI":"10.1097\/j.pbj.0000000000000101","article-title":"Metabolic Syndrome in Type 2 Diabetic Patients: A Review of Current Evidence","volume":"5","author":"Regufe","year":"2020","journal-title":"Porto Biomed. J."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Portero-Otin, M., de la Maza, M.P., and Uribarri, J. (2023). Dietary Advanced Glycation End Products: Their Role in the Insulin Resistance of Aging. Cells, 12.","DOI":"10.3390\/cells12131684"},{"key":"ref_39","unstructured":"International Diabetes Federation (2019). Diabetes Atlas, International Diabetes Federation. [9th ed.]."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nature18642","article-title":"The Genetic Architecture of Type 2 Diabetes","volume":"536","author":"Fuchsberger","year":"2016","journal-title":"Nature"},{"key":"ref_41","first-page":"e49374","article-title":"Diabetes Mellitus and Prevalence of Other Comorbid Conditions: A Systematic Review","volume":"15","author":"Bodke","year":"2023","journal-title":"Cureus"},{"key":"ref_42","unstructured":"International Diabetes Federation (2025). Annual Report 2025, International Diabetes Federation. Available online: https:\/\/idf.org\/news-and-resources\/resources\/annual-report-2025\/."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"491","DOI":"10.2217\/fca-2018-0045","article-title":"Type-2 Diabetes Mellitus and Cardiovascular Disease","volume":"14","author":"Henning","year":"2018","journal-title":"Future Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s11910-022-01236-0","article-title":"Pre-Diabetes, Diabetes, Hyperglycemia, and Stroke: Bittersweet Therapeutic Opportunities","volume":"22","author":"Bruno","year":"2022","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41586-024-07019-6","article-title":"Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology","volume":"627","author":"Suzuki","year":"2024","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/s41588-022-01058-3","article-title":"Multi-Ancestry Genetic Study of Type 2 Diabetes Highlights the Power of Diverse Populations for Discovery and Translation","volume":"54","author":"Mahajan","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_47","first-page":"111","article-title":"Gen\u00e9tica de la Diabetes Mellitus","volume":"2","author":"Wiebe","year":"2011","journal-title":"Nefrolog\u00eda"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2174\/1573399812666151022143502","article-title":"Family History of Type 2 Diabetes: Does Having a Diabetic Parent Increase the Risk?","volume":"13","author":"Papazafiropoulou","year":"2017","journal-title":"Curr. Diabetes Rev."},{"key":"ref_49","first-page":"188","article-title":"Review of the Diabetes Heart Study (DHS) Family of Studies: A Comprehensively Examined Sample for Genetic and Epidemiological Studies of Type 2 Diabetes and Its Complications","volume":"7","author":"Bowden","year":"2010","journal-title":"Rev. Diabet. Stud."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.metabol.2009.07.043","article-title":"PPARG and ADIPOQ Gene Polymorphisms Increase Type 2 Diabetes Mellitus Risk in Asian Indian Sikhs: Pro12Ala Still Remains as the Strongest Predictor","volume":"59","author":"Sanghera","year":"2010","journal-title":"Metabolism"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.diabres.2012.03.012","article-title":"Association of the PPARG Pro12Ala Polymorphism with Type 2 Diabetes and Incident Coronary Heart Disease in a Hong Kong Chinese Population","volume":"97","author":"Ho","year":"2012","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5585","DOI":"10.1007\/s11033-014-3213-7","article-title":"Development of ARMS-PCR Assay for Genotyping of Pro12Ala SNP of PPARG Gene: A Cost-Effective Way for Case-Control Studies of Type 2 Diabetes in Developing Countries","volume":"41","author":"Islam","year":"2014","journal-title":"Mol. Biol. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"20709","DOI":"10.1038\/s41598-022-24931-x","article-title":"Risk of Type 2 Diabetes and KCNJ11 Gene Polymorphisms: A Nested Case-Control Study and Meta-Analysis","volume":"12","author":"Masjoudi","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Song, J., Yang, Y., Mauvais-Jarvis, F., Wang, Y.P., and Niu, T. (2017). KCNJ11, ABCC8 and TCF7L2 Polymorphisms and the Response to Sulfonylurea Treatment in Patients with Type 2 Diabetes: A Bioinformatics Assessment. BMC Med. Genet., 18.","DOI":"10.1186\/s12881-017-0422-7"},{"key":"ref_55","first-page":"694","article-title":"Novel TCF7L2 Familial Linkage and Association with Type 2 Diabetes, Depression, and Their Comorbidity","volume":"27","author":"Amin","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6419","DOI":"10.1093\/hmg\/ddu359","article-title":"TCF7L2 Is a Master Regulator of Insulin Production and Processing","volume":"23","author":"Zhou","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.2337\/db20-0573","article-title":"The Role of TCF7L2 in Type 2 Diabetes","volume":"70","author":"Gragnoli","year":"2021","journal-title":"Diabetes"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.molmed.2010.06.004","article-title":"The Emerging Genetics of Type 2 Diabetes","volume":"16","author":"Bonnefond","year":"2010","journal-title":"Trends Mol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6582","DOI":"10.4238\/2014.August.28.3","article-title":"Racial Disparities in the Association between Diabetes Mellitus-Associated Polymorphic Locus rs4430796 of the HNF1\u03b2 Gene and Prostate Cancer: A Systematic Review and Meta-Analysis","volume":"13","author":"Xiang","year":"2014","journal-title":"Genet. Mol. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"741","DOI":"10.2337\/db09-0920","article-title":"Detailed Investigation of the Role of Common and Low-Frequency WFS1 Variants in Type 2 Diabetes Risk","volume":"59","author":"Fawcett","year":"2010","journal-title":"Diabetes"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Hammad, M.M., Abu-Farha, M., Hebbar, P., Anoop, E., Chandy, B., Melhem, M., Channanath, A., Al-Mulla, F., Thanaraj, T.A., and Abubaker, J. (2023). The miR-668 Binding Site Variant rs1046322 on WFS1 Is Associated with Obesity in Southeast Asians. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1185956"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1507\/endocrj.EJ12-0325","article-title":"Association of rs734312 and rs10010131 Polymorphisms in WFS1 Gene with Type 2 Diabetes Mellitus: A Meta-Analysis","volume":"60","author":"Cheng","year":"2013","journal-title":"Endocr. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1055\/s-0042-1760384","article-title":"Association of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) Gene Polymorphisms with Type 2 Diabetes among Malay Ethnics","volume":"10","author":"Ansari","year":"2023","journal-title":"Glob. Med. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.2174\/1871530320999201126202706","article-title":"Contribution of rs780094 and rs1260326 Polymorphisms in GCKR Gene to Non-Alcoholic Fatty Liver Disease: A Meta-Analysis Involving 26,552 Participants","volume":"21","author":"Li","year":"2021","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Shi, Y., Li, Y., Wang, J., Wang, C., Fan, J., Zhao, J., Yin, L., Liu, X., Zhang, D., and Li, L. (2017). Meta-Analyses of the Association of G6PC2 Allele Variants with Elevated Fasting Glucose and Type 2 Diabetes. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181232"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2147\/DMSO.S284998","article-title":"Association between CDKAL1, HHEX, CDKN2A\/2B and IGF2BP2 Gene Polymorphisms and Susceptibility to Type 2 Diabetes in Uttarakhand, India","volume":"14","author":"Verma","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.trsl.2018.08.003","article-title":"Changes in CDKN2A\/2B Expression Associate with T-Cell Phenotype Modulation in Atherosclerosis and Type 2 Diabetes Mellitus","volume":"203","author":"Piqueras","year":"2019","journal-title":"Transl. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00125-014-3405-7","article-title":"SLC30A8 Mutations in Type 2 Diabetes","volume":"58","author":"Rutter","year":"2015","journal-title":"Diabetologia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.2147\/DMSO.S289642","article-title":"Interactive Effect of IGF2BP2 rs4402960 Variant, Smoking and Type 2 Diabetes","volume":"13","author":"Nfor","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.36740\/WLek202211215","article-title":"The Relevance of rs6777038 and rs6444082 of IGF2BP2 Gene Polymorphism and Type 2 Diabetes Mellitus: A Case Control Study","volume":"75","author":"Mohammed","year":"2022","journal-title":"Wiad. Lek."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Yong, H.J., Xie, G., Liu, C., Wang, W., Naji, A., Irianto, J., and Wang, Y.J. (2021). Gene Signatures of NEUROGENIN3+ Endocrine Progenitor Cells in the Human Pancreas. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.736286"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.2337\/db12-0864","article-title":"Genetic and Molecular Insights into the Role of PROX1 in Glucose Metabolism","volume":"62","author":"Lecompte","year":"2013","journal-title":"Diabetes"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Boesgaard, T.W., Gjesing, A.P., Grarup, N., Rutanen, J., Jansson, P.A., Hribal, M.L., Sesti, G., Fritsche, A., Stefan, N., and Staiger, H. (2009). Variant near ADAMTS9 Known to Associate with Type 2 Diabetes Is Related to Insulin Resistance in Offspring of Type 2 Diabetes Patients\u2014EUGENE2 Study. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007236"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e631","DOI":"10.1002\/mgg3.631","article-title":"IRS1-rs10498210 G\/A and CCR5-59029 A\/G Polymorphisms in Patients with Type 2 Diabetes in Kurdistan","volume":"7","author":"Keshavarzi","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.4239\/wjd.v14.i12.1803","article-title":"Relationship between GCKR Gene rs780094 Polymorphism and Type 2 Diabetes with Albuminuria","volume":"14","author":"Liu","year":"2023","journal-title":"World J. Diabetes"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.2337\/db10-1340","article-title":"FTO, Type 2 Diabetes, and Weight Gain throughout Adult Life: A Meta-Analysis of 41,504 Subjects from the Scandinavian HUNT, MDC, and MPP Studies","volume":"60","author":"Hertel","year":"2011","journal-title":"Diabetes"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"147791","DOI":"10.1016\/j.gene.2023.147791","article-title":"FTO Gene Variants (rs9939609, rs8050136 and rs17817449) and Type 2 Diabetes Mellitus Risk: A Meta-Analysis","volume":"887","author":"Zouine","year":"2023","journal-title":"Gene"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1080\/10408398.2020.1850416","article-title":"Nutrigenetics, Nutrigenomics and Phenotypic Outcomes of Dietary Low-Dose Alcohol Consumption in the Suppression and Induction of Cancer Development: Evidence from in Vitro Studies","volume":"62","author":"Caradonna","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_79","unstructured":"Egbuna, C., and Ifemeje, J.C. (2023). Nutrigenomics and Nutrigenetics: Importance in Health and Diseases. Role of Nutrigenomics in Modern-Day Healthcare and Drug Discovery, Elsevier."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Felisbino, K., Granzotti, J.G., Bello-Santos, L., and Guiloski, I.C. (2021). Nutrigenomics in Regulating the Expression of Genes Related to Type 2 Diabetes Mellitus. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.699220"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"170","DOI":"10.4093\/dmj.2023.0272","article-title":"One-Carbon Metabolism Nutrients, Genetic Variation, and Diabetes Mellitus","volume":"48","author":"Zhu","year":"2024","journal-title":"Diabetes Metab. J."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Bernasocchi, T., and Mostoslavsky, R. (2024). Subcellular One Carbon Metabolism in Cancer, Aging and Epigenetics. Front. Epigenet. Epigenom., 2.","DOI":"10.3389\/freae.2024.1451971"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Bortz, J., and Obeid, R. (2025). The Shuttling of Methyl Groups between Folate and Choline Pathways. Nutrients, 17.","DOI":"10.3390\/nu17152495"},{"key":"ref_84","first-page":"329","article-title":"A Two-Way Relationship between Histone Acetylation and Metabolism","volume":"50","author":"Charalambous","year":"2025","journal-title":"Trends Biochem. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1111\/brv.13049","article-title":"Specific Regulation of Epigenome Landscape by Metabolic Enzymes and Metabolites","volume":"99","author":"Yu","year":"2024","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Li, X., Geng-Ji, J.J., Quan, Y.Y., Qi, L.M., Sun, Q., Huang, Q., Xie, X., Jiang, H.-M., Sun, Z.-J., and Liu, H.-M. (2022). Role of Potential Bioactive Metabolites from Traditional Chinese Medicine for Type 2 Diabetes Mellitus: An Overview. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1023713"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Susilawati, E., Levita, J., Susilawati, Y., and Sumiwi, S.A. (2023). Review of the Case Reports on Metformin, Sulfonylurea, and Thiazolidinedione Therapies in Type 2 Diabetes Mellitus Patients. Med. Sci., 11.","DOI":"10.3390\/medsci11030050"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.2174\/1568026621666210509161059","article-title":"Bioactive Compounds Effective Against Type 2 Diabetes Mellitus: A Systematic Review","volume":"21","author":"Egbuna","year":"2021","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s40200-021-00943-8","article-title":"Flavonoids, Alkaloids and Terpenoids: A New Hope for the Treatment of Diabetes Mellitus","volume":"21","author":"Singh","year":"2022","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"155638","DOI":"10.1016\/j.phymed.2024.155638","article-title":"Terpenoids as Potential Phytoconstituent in the Treatment of Diabetes: From Preclinical to Clinical Advancement","volume":"129","author":"Roy","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2174\/1871530320666200821124817","article-title":"Natural Alkaloids and Diabetes Mellitus: A Review","volume":"21","author":"Ajebli","year":"2021","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"7000","DOI":"10.1021\/acs.jafc.1c01465","article-title":"Bioactive Dietary Fibers Selectively Promote Gut Microbiota to Exert Antidiabetic Effects","volume":"69","author":"Nie","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Mazhar, M., Zhu, Y., and Qin, L. (2023). The Interplay of Dietary Fibers and Intestinal Microbiota Affects Type 2 Diabetes by Generating Short-Chain Fatty Acids. Foods, 12.","DOI":"10.3390\/foods12051023"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Pivari, F., Mingione, A., Brasacchio, C., and Soldati, L. (2019). Curcumin and Type 2 Diabetes Mellitus: Prevention and Treatment. Nutrients, 11.","DOI":"10.3390\/nu11081837"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"11999","DOI":"10.1039\/D2FO02625B","article-title":"Effects of Curcumin, a Bioactive Component of Turmeric, on Type 2 Diabetes Mellitus and Its Complications: An Updated Review","volume":"13","author":"Bozkurt","year":"2022","journal-title":"Food Funct."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1111\/wrr.13115","article-title":"Procyanidins: A Promising Anti-Diabetic Agent with Potential Benefits on Glucose Metabolism and Diabetes Complications","volume":"31","author":"Qaed","year":"2023","journal-title":"Wound Repair Regen."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Li, M., Liu, H., Fan, Y., and Liu, H.H. (2025). The Application of Procyanidins in Diabetes and Its Complications: A Review of Preclinical Studies. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1532246"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s13668-023-00475-y","article-title":"NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health","volume":"12","author":"Alegre","year":"2023","journal-title":"Curr. Nutr. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"101936","DOI":"10.1016\/j.arr.2023.101936","article-title":"Sirtuins, Resveratrol and the Intertwining Cellular Pathways Connecting Them","volume":"88","author":"Ungurianu","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4163","DOI":"10.1038\/s41598-018-22388-5","article-title":"Natural Polyphenols as Sirtuin 6 Modulators","volume":"8","author":"Tyni","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3153","DOI":"10.1007\/s10068-024-01664-3","article-title":"Fatty Acids and Epigenetics in Health and Diseases","volume":"33","author":"Chung","year":"2024","journal-title":"Food Sci. Biotechnol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"103115","DOI":"10.1016\/j.arr.2026.103115","article-title":"Epigenetic Remodeling Induced by Fatty Acids: Chromatin Modifications and Cellular Senescence during Lipid Overload","volume":"118","year":"2026","journal-title":"Ageing Res. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Murru, E., Manca, C., Carta, G., and Banni, S. (2022). Impact of Dietary Palmitic Acid on Lipid Metabolism. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.861664"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Santa-Mar\u00eda, C., L\u00f3pez-Enr\u00edquez, S., Montserrat-de la Paz, S., Geniz, I., Reyes-Quiroz, M.E., Moreno, M., Palomares, F., Sobrino, F., and Alba, G. (2023). Update on Anti-Inflammatory Molecular Mechanisms Induced by Oleic Acid. Nutrients, 15.","DOI":"10.3390\/nu15010224"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"101165","DOI":"10.1016\/j.plipres.2022.101165","article-title":"Polyunsaturated Fatty Acids and Fatty Acid-Derived Lipid Mediators: Recent Advances in the Understanding of Their Biosynthesis, Structures, and Functions","volume":"86","author":"Dyall","year":"2022","journal-title":"Prog. Lipid Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e70019","DOI":"10.14814\/phy2.70019","article-title":"Overview of the Therapeutic Efficacy of Marine Fish Oil in Managing Obesity and Associated Metabolic Disorders","volume":"12","author":"Kar","year":"2024","journal-title":"Physiol. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Su\u00e1rez, R., Chapela, S.P., \u00c1lvarez-C\u00f3rdova, L., Bautista-Valarezo, E., Sarmiento-Andrade, Y., Verde, L., Frias-Toral, E., and Sarno, G. (2023). Epigenetics in Obesity and Diabetes Mellitus: New Insights. Nutrients, 15.","DOI":"10.3390\/nu15040811"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.coph.2020.10.008","article-title":"Epigenetics in \u03b2-Cell Adaptation and Type 2 Diabetes","volume":"55","author":"Kim","year":"2020","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Yang, Y., Luan, Y., Feng, Q., Chen, X., Qin, B., Ren, K., and Luan, Y. (2022). Epigenetics and Beyond: Targeting Histone Methylation to Treat Type 2 Diabetes Mellitus. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.807413"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"113984","DOI":"10.1016\/j.biopha.2022.113984","article-title":"Novel Histone Post-Translational Modifications in Diabetes and Complications of Diabetes: The Underlying Mechanisms and Implications","volume":"156","author":"Li","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.2174\/0929867329666220802090446","article-title":"A Recent Update on the Epigenetic Repertoire and Chromatin Modifying Therapy in Diabetes Mellitus: A Comprehensive Review","volume":"30","author":"Wang","year":"2023","journal-title":"Curr. Med. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Jazieh, C., Arabi, T.Z., Asim, Z., Sabbah, B.N., Alsaud, A.W., Alkattan, K., and Yaqinuddin, A. (2024). Unraveling the Epigenetic Fabric of Type 2 Diabetes Mellitus: Pathogenic Mechanisms and Therapeutic Implications. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1295967"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"8040","DOI":"10.1038\/s41467-023-43719-9","article-title":"Genes with Epigenetic Alterations in Human Pancreatic Islets Impact Mitochondrial Function, Insulin Secretion, and Type 2 Diabetes","volume":"14","author":"Ofori","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.freeradbiomed.2020.12.025","article-title":"The Metabolic-Epigenetic Nexus in Type 2 Diabetes Mellitus","volume":"170","author":"Davison","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.cmet.2019.03.009","article-title":"Epigenetics in Human Obesity and Type 2 Diabetes","volume":"29","author":"Ling","year":"2019","journal-title":"Cell Metab."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"115732","DOI":"10.1016\/j.bcp.2023.115732","article-title":"Metformin-Mediated Epigenetic Modifications in Diabetes and Associated Conditions: Biological and Clinical Relevance","volume":"215","author":"Giordo","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"C570","DOI":"10.1152\/ajpcell.00201.2022","article-title":"Epigenetic Modifications in Metabolic Memory: What Are the Memories, and Can We Erase Them?","volume":"323","author":"Chen","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"F327","DOI":"10.1152\/ajprenal.00115.2024","article-title":"Update: The Role of Epigenetics in the Metabolic Memory of Diabetic Complications","volume":"327","author":"Chen","year":"2024","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Milluzzo, A., Maugeri, A., Barchitta, M., Sciacca, L., and Agodi, A. (2021). Epigenetic Mechanisms in Type 2 Diabetes Retinopathy: A Systematic Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910502"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"804","DOI":"10.2337\/dbi19-0016","article-title":"MicroRNA Networks in Pancreatic Islet Cells: Normal Function and Type 2 Diabetes","volume":"69","author":"Eliasson","year":"2020","journal-title":"Diabetes"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1007\/s11739-026-04281-6","article-title":"MicroRNAs in Type 2 Diabetes Mellitus and Its Cardiovascular Complications: Mechanistic Insights and Translational Potential","volume":"21","author":"Corrao","year":"2026","journal-title":"Intern. Emerg. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s00125-022-05809-z","article-title":"MicroRNA Biomarkers of Type 2 Diabetes: Evidence Synthesis from Meta-Analyses and Pathway Modelling","volume":"66","author":"Zhu","year":"2023","journal-title":"Diabetologia"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00439-023-02616-3","article-title":"Genetics and Epigenetics of Diabetes and Its Complications in India","volume":"143","author":"Priyadarshini","year":"2024","journal-title":"Hum. Genet."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"10372","DOI":"10.1038\/s41598-023-37550-x","article-title":"Analysis of Age-Dependent Gene-Expression in Human Tissues for Studying Diabetes Comorbidities","volume":"13","author":"Guzzi","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41574-022-00671-w","article-title":"Epigenetics of Type 2 Diabetes Mellitus and Weight Change\u2014A Tool for Precision Medicine?","volume":"18","author":"Ling","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"109037","DOI":"10.1016\/j.jnutbio.2022.109037","article-title":"A Comprehensive Review on High-Fat Diet-Induced Diabetes Mellitus: An Epigenetic View","volume":"107","author":"Prasad","year":"2022","journal-title":"J. Nutr. Biochem."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Parrillo, L., Spinelli, R., Nicol\u00f2, A., Longo, M., Mirra, P., Raciti, G.A., Miele, C., and Beguinot, F. (2019). Nutritional Factors, DNA Methylation, and Risk of Type 2 Diabetes and Obesity: Perspectives and Challenges. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20122983"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41366-020-00729-7","article-title":"DNA Methylation in Adipocytes from Visceral and Subcutaneous Adipose Tissue Influences Insulin-Signaling Gene Expression in Obese Individuals","volume":"45","author":"Cierzniak","year":"2021","journal-title":"Int. J. Obes."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"106031","DOI":"10.1016\/j.biocel.2021.106031","article-title":"Histone Modifications Influence the Insulin-Signaling Genes and Are Related to Insulin Resistance in Human Adipocytes","volume":"137","author":"Cierzniak","year":"2021","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Franzago, M., Pilenzi, L., Di Rado, S., Vitacolonna, E., and Stuppia, L. (2022). The Epigenetic Aging, Obesity, and Lifestyle. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.985274"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"105922","DOI":"10.1016\/j.fitote.2024.105922","article-title":"Bioactive Alkaloidal and Phenolic Phytochemicals as Promising Epidrugs for Diabetes Mellitus 2: A Review of Recent Development","volume":"175","author":"Ayipo","year":"2024","journal-title":"Fitoterapia"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"117010","DOI":"10.1016\/j.biopha.2024.117010","article-title":"Histone Deacetylases and Inhibitors in Diabetes Mellitus and Its Complications","volume":"177","author":"Wang","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"175328","DOI":"10.1016\/j.ejphar.2022.175328","article-title":"Histone Deacetylase Inhibitors as Antidiabetic Agents: Advances and Opportunities","volume":"935","author":"Sonthalia","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Martinez-Moreno, J.M., Fontecha-Barriuso, M., Martin-Sanchez, D., Guerrero-Mauvecin, J., Goma-Garces, E., Fernandez-Fernandez, B., Carriazo, S., Sanchez-Ni\u00f1o, M.D., Ramos, A.M., and Ruiz-Ortega, M. (2020). Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114113"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1001\/jama.2020.3308","article-title":"Effect of Apabetalone Added to Standard Therapy on Major Adverse Cardiovascular Events in Patients with Recent Acute Coronary Syndrome and Type 2 Diabetes: A Randomized Clinical Trial","volume":"323","author":"Ray","year":"2020","journal-title":"JAMA"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Nord, J.A., Wynia-Smith, S.L., Gehant, A.L., Jones Lipinski, R.A., Naatz, A., Rioja, I., Prinjha, R.K., Corbett, J.A., and Smith, B.C. (2022). N-Terminal BET Bromodomain Inhibitors Disrupt a BRD4-P65 Interaction and Reduce Inducible Nitric Oxide Synthase Transcription in Pancreatic \u03b2-Cells. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.923925"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Rong, Y., Bao, W., Shan, Z., Liu, J., Yu, X., Xia, S., Gao, H., Wang, X., Yao, P., and Hu, F.B. (2013). Increased MicroRNA-146a Levels in Plasma of Patients with Newly Diagnosed Type 2 Diabetes Mellitus. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073272"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s00125-025-06581-6","article-title":"Pharmacological Therapies for Type 2 Diabetes: Future Approaches","volume":"69","author":"Bailey","year":"2026","journal-title":"Diabetologia"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1016\/j.jmb.2019.09.017","article-title":"Micro(RNA) Management and Mismanagement of the Islet","volume":"432","author":"Eliasson","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e70175","DOI":"10.1002\/dmrr.70175","article-title":"MicroRNAs in Obesity-Associated Metabolic Inflammation: From Molecular Mechanisms to Clinical Translation","volume":"42","author":"Mao","year":"2026","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e1768","DOI":"10.1002\/wrna.1768","article-title":"Innovative Approaches in Transforming microRNAs into Therapeutic Tools","volume":"14","author":"Samad","year":"2023","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1111\/dom.12688","article-title":"Extracellular microRNAs and Endothelial Hyperglycaemic Memory: A Therapeutic Opportunity?","volume":"18","author":"Prattichizzo","year":"2016","journal-title":"Diabetes Obes. Metab."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Moraes, F.C., Pichon, C., Letourneur, D., and Chaubet, F. (2021). miRNA Delivery by Nanosystems: State of the Art and Perspectives. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111901"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41571-025-01114-x","article-title":"MicroRNAs in Oncology: A Translational Perspective in the Era of AI","volume":"23","author":"Jurj","year":"2026","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"109211","DOI":"10.1016\/j.jdiacomp.2025.109211","article-title":"The miR-200 Family in Type 2 Diabetes: Therapeutic and Biomarker Perspectives","volume":"40","author":"Ajonijebu","year":"2026","journal-title":"J. Diabetes Complicat."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.2337\/db25-0977","article-title":"MicroRNAs in Islet Biology and Diabetes: Progress, Gaps, and Opportunities","volume":"75","year":"2026","journal-title":"Diabetes"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1093\/hmg\/ddad084","article-title":"Epigenome-Wide Methylation Study Identified Two Novel CpGs Associated with T2DM Risk and a Network of Co-Methylated CpGs Capable of Patient\u2019s Classifications","volume":"32","author":"Giri","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1007\/s00125-017-4497-7","article-title":"DNA Methylation Markers Associated with Type 2 Diabetes, Fasting Glucose and HbA1c Levels: A Systematic Review and Replication in a Case-Control Sample of the Lifelines Study","volume":"61","author":"Walaszczyk","year":"2018","journal-title":"Diabetologia"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"885","DOI":"10.2217\/epi-2018-0159","article-title":"Critical Evaluation of the DNA-Methylation Markers ABCG1 and SREBF1 for Type 2 Diabetes Stratification","volume":"11","author":"Krause","year":"2019","journal-title":"Epigenomics"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13148-024-01670-6","article-title":"DNA Methylation and Type 2 Diabetes: A Systematic Review","volume":"16","author":"Nadiger","year":"2024","journal-title":"Clin. Epigenet."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"eaaz1803","DOI":"10.1126\/scitranslmed.aaz1803","article-title":"Epigenetic Markers Associated with Metformin Response and Intolerance in Drug-Na\u00efve Patients with Type 2 Diabetes","volume":"12","author":"Perfilyev","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/1753-0407.13431","article-title":"A Review of Micro RNAs Changes in T2DM in Animals and Humans","volume":"15","author":"Afsharmanesh","year":"2023","journal-title":"J. Diabetes"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.trsl.2022.03.008","article-title":"Circulating microRNAs as Clinically Useful Biomarkers for Type 2 Diabetes Mellitus: miRNomics from Bench to Bedside","volume":"247","author":"Grieco","year":"2022","journal-title":"Transl. Res."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Zeinali, F., Aghaei Zarch, S.M., Jahan-Mihan, A., Kalantar, S.M., Vahidi Mehrjardi, M.Y., Fallahzadeh, H., Hosseinzadeh, M., Rahmanian, M., and Mozaffari-Khosravi, H. (2021). Circulating microRNA-122, microRNA-126-3p and microRNA-146a Are Associated with Inflammation in Patients with Pre-Diabetes and Type 2 Diabetes Mellitus: A Case Control Study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251697"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Willmer, T., Johnson, R., Louw, J., and Pheiffer, C. (2018). Blood-Based DNA Methylation Biomarkers for Type 2 Diabetes: Potential for Clinical Applications. Front. Endocrinol., 9, Correction in Front. Endocrinol.\u00a02019, 10, 1.","DOI":"10.3389\/fendo.2019.00001"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"117856","DOI":"10.1016\/j.cca.2024.117856","article-title":"Epigenetics of Diabetes: A Bioinformatic Approach","volume":"557","author":"Antonius","year":"2024","journal-title":"Clin. Chim. Acta"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"120104","DOI":"10.1016\/j.cca.2024.120104","article-title":"The Potential of Circulating Free DNA of Methylated IGFBP as a Biomarker for Type 2 Diabetes Mellitus: A Comprehensive Review","volume":"567","author":"Belinda","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1111\/joim.13306","article-title":"Connecting the Epigenome, Metabolome and Proteome for a Deeper Understanding of Disease","volume":"290","author":"Suhre","year":"2021","journal-title":"J. Intern. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1038\/s41467-023-37837-7","article-title":"DNA Methylation Markers for Kidney Function and Progression of Diabetic Kidney Disease","volume":"14","author":"Li","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.2337\/db16-0996","article-title":"Whole-Genome Bisulfite Sequencing of Human Pancreatic Islets Reveals Novel Differentially Methylated Regions in Type 2 Diabetes Pathogenesis","volume":"66","author":"Volkov","year":"2017","journal-title":"Diabetes"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"2297860","DOI":"10.1080\/19490976.2023.2297860","article-title":"Multi-Omic Approaches for Host-Microbiome Data Integration","volume":"16","author":"Chetty","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s13148-024-01692-0","article-title":"Exploring Histone Deacetylases in Type 2 Diabetes Mellitus: Pathophysiological Insights and Therapeutic Avenues","volume":"16","author":"Kumar","year":"2024","journal-title":"Clin. Epigenet."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/s10020-024-00939-z","article-title":"Epigenetic Mechanisms in Cardiovascular Complications of Diabetes: Towards Future Therapies","volume":"30","author":"Damiano","year":"2024","journal-title":"Mol. Med."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Deberneh, H.M., and Kim, I. (2021). Prediction of Type 2 Diabetes Based on Machine Learning Algorithm. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18063317"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"e00472","DOI":"10.1002\/edm2.472","article-title":"Machine-Learning Algorithms in Screening for Type 2 Diabetes Mellitus: Data from Fasa Adults Cohort Study","volume":"7","author":"Karmand","year":"2024","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1038\/s41598-024-52550-1","article-title":"An Artificial Neural Network Model for Evaluating the Risk of Hyperuricaemia in Type 2 Diabetes Mellitus","volume":"14","author":"Chen","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"e13890","DOI":"10.1111\/eci.13890","article-title":"Big Data and Machine Learning to Tackle Diabetes Management","volume":"53","author":"Pina","year":"2023","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S2213-8587(18)30051-2","article-title":"Novel Subgroups of Adult-Onset Diabetes and Their Association with Outcomes: A Data-Driven Cluster Analysis of Six Variables","volume":"6","author":"Ahlqvist","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"e004191","DOI":"10.1136\/bmjdrc-2024-004191","article-title":"Identifying Subtypes of Type 2 Diabetes Mellitus with Machine Learning: Development, Internal Validation, Prognostic Validation and Medication Burden in Linked Electronic Health Records in 420,448 Individuals","volume":"12","author":"Mizani","year":"2024","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s00125-022-05652-2","article-title":"Epigenome-Wide Association Study of Incident Type 2 Diabetes: A Meta-Analysis of Five Prospective European Cohorts","volume":"65","author":"Fraszczyk","year":"2022","journal-title":"Diabetologia"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Lv, B., Bao, X., Li, P., Lian, J., Wu, Y., An, T., Zhang, J., Yang, X., Wang, T., and Zhu, J. (2020). Transcriptome Sequencing Analysis of Peripheral Blood of Type 2 Diabetes Mellitus Patients with Thirst and Fatigue. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.558344"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Alamro, H., Bajic, V., Macvanin, M.T., Isenovic, E.R., Gojobori, T., Essack, M., and Gao, X. (2023). Type 2 Diabetes Mellitus and Its Comorbidity, Alzheimer\u2019s Disease: Identifying Critical MicroRNA Using Machine Learning. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1084656"},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Wu, M., and Zhang, Y. (2022). Combining Bioinformatics, Network Pharmacology and Artificial Intelligence to Predict the Mechanism of Celastrol in the Treatment of Type 2 Diabetes. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1030278"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"14637","DOI":"10.1038\/s41598-024-64846-3","article-title":"Predicting Type 2 Diabetes via Machine Learning Integration of Multiple Omics from Human Pancreatic Islets","volume":"14","author":"Perfilyev","year":"2024","journal-title":"Sci. Rep."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3206\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T08:25:48Z","timestamp":1791879948000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":174,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["nu18193206"],"URL":"https:\/\/doi.org\/10.3390\/nu18193206","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]}}}