Social Determinants and Epigenetic Mechanisms in the Syndemic of Type 2 Diabetes Mellitus: An Integrative Review
DOI:
https://doi.org/10.66201/ss.v1.11Keywords:
Social Determinants of Health, Epigenomics, DNA Methylation, Type 2 Diabetes Mellitus, Psychosocial Stress, Social Justice, SyndemicAbstract
Introduction: Type 2 diabetes mellitus (T2DM) represents a syndemic public health crisis, where social adversity translates into persistent biological dysfunction. Epigenetics emerges as the mechanistic link that explains how the environment “gets under the skin” to alter metabolism. The aim of this review was to synthesize the current scientific evidence on the epigenetic mechanisms (DNA methylation, RNA modifications, and microRNAs) that mediate the relationship between the social determinants of health and the pathogenesis of T2DM.
Methodology: An integrative review was conducted based on the Whittemore and Knafl framework. A systematic search was performed in PubMed, Scopus, and Web of Science (2015–2025). Methodological quality was assessed using the Mixed Methods Appraisal Tool (MMAT).
Results: Early trauma was identified as inducing demethylation of the FKBP5 gene and silencing of NR3C1, leading to systemic glucocorticoid resistance and meta-inflammation. Structural poverty and food insecurity are associated with hypermethylation of SLC2A4 (GLUT4) and PPARG, physically blocking glucose transport and promoting lipotoxicity. The urban exposome and chronodisruption accelerate biological aging (DNAmAge) and alter hepatic m6A methylation. Intergenerational transmission of metabolic risk via IGF2 and circulating microRNAs (miR-375, miR-29a) was also confirmed.
Conclusions: Type 2 diabetes is the molecular embodiment of social inequality. Epigenetic markers act as structural biological barriers that limit the effectiveness of interventions focused solely on individual behavior. Effective diabetes prevention requires public policies that mitigate allostatic stress and material deprivation.
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Copyright (c) 2026 Aliceana Adao Maciel, Larissa Roberta Pereira Rodrigues, Jade Da Mota Britto, Davi Bezerra Alves Gomes Lourenço, Natália Saionara De Oliveira Sousa, Mariela Santos Lombardo, Vanessa Polyana De Sousa Vasco Pinheiro
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