Department of Molecular Biosciences and Bioengineering, University of Hawaii, Honolulu, HI, 96822, USA.
Department of Native Hawaiian Health, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, 96813, USA.
Clin Epigenetics. 2022 Jul 18;14(1):91. doi: 10.1186/s13148-022-01307-6.
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.
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.
Our pilot study provides preliminary evidence of changes to inflammatory monocyte activity, potentially driven by epigenetic modifications, 3 months following a DM-specific SSP intervention. These novel alterations in the trajectory of monocyte inflammatory states were identified at loci that regulate transcription of immune and metabolic genes in high-risk Native Hawaiians with DM, suggesting a relationship between improvements in psychosocial behaviors and shifts in the immunoepigenetic patterns following a diabetes-specific SSP. Further research is warranted to investigate how social support influences systemic inflammation via immunoepigenetic modifications in chronic inflammatory diseases such as DM.
夏威夷原住民患 2 型糖尿病（DM）的比例过高，这是一种慢性代谢性非传染性疾病，其特征是高血糖和全身炎症。持续的全身炎症经常导致与 DM 相关的多种合并症的级联反应，包括心血管疾病、微血管并发症和肾功能障碍。然而，很少有研究探讨细胞水平的慢性炎症与 DM 的标准治疗方法（如糖尿病特异性生活方式和社会支持教育）之间的联系，后者被公认为糖尿病护理临床标准的基石。这项初步研究旨在探讨在高危夏威夷原住民 DM 患者中进行为期 3 个月的糖尿病特异性社会支持计划后，使用表观遗传、免疫和临床措施评估单核细胞炎症与标准 DM 治疗之间的关联。
在 16 名患有 DM 的夏威夷原住民成年人中，随机选择 8 名个体外周血单核细胞（PBMCs）中的单核细胞进行表观基因组分析。使用 Illumina HumanMethylation450 BeadChip 微阵列，在 DM 特异性社会支持计划（DM-SSP）前后基线和 3 个月时，在参与者的单核细胞中鉴定出 1061 个差异甲基化位点（DML）。基因本体分析表明，这些 DML 富集在参与免疫、代谢和心血管代谢途径的基因中，其中一部分基因的表达也存在显著差异。体外免疫功能分析显示，与基线相比，DM-SSP 后有改善，表现为单核细胞分泌的白细胞介素 1β 和 IL-6 减少。DM-SSP 后细胞因子分泌的变化与干预时间点之间单核细胞免疫相关基因的甲基化和基因表达状态的变化显著相关。
我们的初步研究提供了初步证据，表明在 DM 特异性 SSP 干预 3 个月后，炎症性单核细胞活性发生变化，可能是由表观遗传修饰驱动的。在高危夏威夷原住民 DM 患者中，这些单核细胞炎症状态轨迹的新变化发生在调节免疫和代谢基因转录的基因座上，表明在糖尿病特异性 SSP 后，心理社会行为的改善与免疫表观遗传模式的转变之间存在关系。需要进一步研究以探讨社会支持如何通过 DM 等慢性炎症性疾病的免疫表观遗传修饰来影响全身炎症。
