Shifts in the immunoepigenomic landscape of monocytes in response to a diabetes-specific social support intervention: a pilot study among Native Hawaiian adults with diabetes

• Published in: Clinical Epigenetics
• Main Authors: Dye, Christian K., Corley, Michael J., Ing, Claire, Lum-Jones, Annette, Li, Dongmei, Mau, Marjorie K. L. M., Maunakea, Alika K.
• Format: Text
• Language: English
• Published: BioMed Central 2022
• Subjects: Research; DML
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295496/; http://www.ncbi.nlm.nih.gov/pubmed/35851422; https://doi.org/10.1186/s13148-022-01307-6

BACKGROUND: Native Hawaiians are disproportionately affected by type 2 diabetes mellitus (DM), a chronic metabolic, non-communicable disease characterized by hyperglycemia and systemic inflammation. Unrelenting systemic inflammation frequently leads to a cascade of multiple comorbidities associated with DM, including cardiovascular disease, microvascular complications, and renal dysfunction. Yet few studies have examined the link between chronic inflammation at a cellular level and its relationship to standard DM therapies such as diabetes-specific lifestyle and social support education, well recognized as the cornerstone of clinical standards of diabetes care. This pilot study was initiated to explore the association of monocyte inflammation using epigenetic, immunologic, and clinical measures following a 3-month diabetes-specific social support program among high-risk Native Hawaiian adults with DM. RESULTS: From a sample of 16 Native Hawaiian adults with DM, monocytes enriched from peripheral blood mononuclear cells (PBMCs) of 8 individuals were randomly selected for epigenomic analysis. Using the Illumina HumanMethylation450 BeadChip microarray, 1,061 differentially methylated loci (DML) were identified in monocytes of participants at baseline and 3 months following a DM-specific social support program (DM-SSP). Gene ontology analysis showed that these DML were enriched within genes involved in immune, metabolic, and cardiometabolic pathways, a subset of which were also significantly differentially expressed. Ex vivo analysis of immune function showed improvement post-DM-SSP compared with baseline, characterized by attenuated interleukin 1β and IL-6 secretion from monocytes. Altered cytokine secretion in response to the DM-SSP was significantly associated with changes in the methylation and gene expression states of immune-related genes in monocytes between intervention time points. CONCLUSIONS: Our pilot study provides preliminary evidence of changes to inflammatory monocyte activity, potentially driven by ...