{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:02:51Z","timestamp":1790089371736,"version":"4.0.1"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Albanian University Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Precision nutrition has emerged as a promising strategy for the prevention of type 2 diabetes mellitus (T2DM) by targeting molecular pathways underlying insulin resistance and impaired glucose metabolism. Accumulating evidence indicates that dietary patterns, caloric intake, and specific nutrients can modulate gene expression and epigenetic mechanisms involved in insulin signaling, inflammation, and energy homeostasis. This narrative review synthesizes recent human and experimental studies (2025\u20132026) examining how dietary components influence transcriptional and epigenetic regulation of insulin signaling and glucose metabolism in the context of T2DM prevention. A total of 29 peer-reviewed studies were included, encompassing dietary patterns, macronutrient manipulation, micronutrient and bioactive supplementation, and gene\u2013diet interactions. Very-low-calorie diets consistently induced coordinated modulation of key metabolic genes, including downregulation of glucose transporter type 4 (GLUT4) and upregulation of PDK4, CPT1, and AMPK, reflecting a metabolic shift toward enhanced fatty acid oxidation and improved insulin sensitivity. In contrast, high-fat and fructose-rich diets promoted proinflammatory gene expression and immune activation, contributing to insulin resistance. Plant-based and vegan dietary patterns were associated with reduced epigenetic aging and improved insulin sensitivity through DNA methylation changes. Targeted interventions, including vitamin D combined with probiotics, dietary fiber, nucleotides, and trace elements such as copper, further demonstrated favorable transcriptional and epigenetic effects linked to improved glycemic control. Collectively, these findings highlight diet-driven modulation of insulin signaling and glucose metabolism at the molecular level and support nutrigenomics-guided precision nutrition as a viable preventive approach for T2DM. Integrating genetic and epigenetic insights into dietary strategies may enable more personalized and effective interventions to curb the growing global burden of type 2 diabetes.<\/jats:p>","DOI":"10.3390\/ijms27041631","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T08:15:54Z","timestamp":1770624954000},"page":"1631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Precision Nutrition in Type 2 Diabetes Prevention Through Molecular Nutrigenomic and Epigenetic Modulation of Insulin Signaling and Glucose Metabolism"],"prefix":"10.3390","volume":"27","author":[{"given":"Daniel","family":"Rumui","sequence":"first","affiliation":[{"name":"School of Medicine, Faculty of Medicine, Ciputra University of Surabaya, Surabaya 60219, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Dama","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, Albanian University, 1017 Tirana, Albania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Era","family":"Gorica","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, Albanian University, 1017 Tirana, Albania"},{"name":"Department of Cardiac Surgery, Faculty of Medicine, University Hospital Z\u00fcrich, University of Z\u00fcrich, Wagistrasse 12, 8952 Schlieren, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Samuel","family":"Halim","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Medicine, Ciputra University of Surabaya, Surabaya 60219, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5162-416X","authenticated-orcid":false,"given":"Apple Faith","family":"Setiawan","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Medicine, Ciputra University of Surabaya, Surabaya 60219, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xandra Christensen","family":"Tjia","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Medicine, Ciputra University of Surabaya, Surabaya 60219, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Hadinata","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Medicine, Ciputra University of Surabaya, Surabaya 60219, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dante Saksono","family":"Harbuwono","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Referral Hospital, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2151-0854","authenticated-orcid":false,"given":"Fahrul","family":"Nurkolis","sequence":"additional","affiliation":[{"name":"Master of Basic Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya 60131, Indonesia"},{"name":"Medical Research Center of Indonesia, Surabaya 60281, Indonesia"},{"name":"Institute for Research and Community Service, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-3327","authenticated-orcid":false,"given":"Antonello","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano, 49, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hwalla, N., Jaafar, Z., and Sawaya, S. 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