Evaluating the Impact of a Community-Based Diabetes Intervention on Monocyte Epigenomes of Native Hawaiians and Pacific Peoples

Abstract

Diabetes mellitus disproportionally affects Native Hawaiians and Pacific Islanders. To reverse these disparities, the Partners in Care (PIC) community-based diabetes self-management intervention program was established to improve glycemic control. Little is known about the molecular mechanisms associated with the change in glycemic control in the PIC intervention. The objective of this study was to understand how inflammatory states, and underlying epigenetic processes, of monocytes from peripheral blood mononuclear cells (PBMC) respond to behavioral changes implemented by the PIC. To test this hypothesis, PBMCs were isolated from whole blood samples that were collected from sixteen type 2 diabetic patients with A1c > 7% pre- and post-PIC intervention over three months. Monocytes were isolated and their inflammatory response characterized using flow cytometry. Infinium HumanMethylation 450 BeadChip technology was used to survey the DNA methylomes of monocytes pre- and postintervention. Results showed genome-wide differential DNA methylation patterns in the monocytes. These changes corresponded to a reduction of monocyte inflammatory response and improved A1c level. Differentially methylated loci correlate with inflammatory and glucose metabolism gene networks. Together, these results suggest that epigenetic processes that regulate the pro-inflammatory response of monocytes are linked to glycemic control and can be altered by behavioral changes. The observed DNA methylated loci may be used to monitor an individual’s response to a diabetes self-management program and the potential long-lasting influences of the program on their overall health.