Diabetes and periodontitis

Abstract

Periodontal disease is known as the sixth complication of diabetes. Recently, many clinical and epidemiologic reports have shown that local periodontal inflammation induces systemic micro-inflammation, contributing to insulin resistance and increasing the risk of cardiovascular diseases. We have used in vitro and in vivo studies to address the amplification mechanism of periodontal inflammation from the viewpoint of adipocyte-macrophage interaction. Our studies suggest that inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), are secreted from monocytes and macrophages that are stimulated by periodontal pathogen-derived Toll-like receptor ligands, such as lipopolysaccharides (LPS). TNFα then activates both adipocytes and infiltrated macrophages, thereby amplifying micro-inflammation through the synergistic production of inflammatory cytokines, including interleukin-6 and monocyte chemoattractant protein-1. Additionally, the expression of chemokine (C-C motif) ligand 19 (CCL19), involved in homing of dendritic cells, was found to be markedly upregulated in adipocytes co-cultured with LPS-stimulated macrophages. In vivo studies suggest that CCR7-CCL19 signaling possibly plays a critical role in adipose tissue metabolism through infiltration of immune cells, such as dendritic cells. Furthermore, the Hiroshima study, a clinical intervention study on diabetic patients receiving periodontal treatment, clearly showed that periodontal treatment combined with local oral antibiotic administration could improve glycated hemoglobin levels in subjects with a high-sensitivity C-reactive protein level > 500 ng/ml and a body mass index of approximately 25 kg/m2. A series of our studies suggests that periodontal treatment could improve glycemic control in diabetic patients with mild obesity.