Mitochondrial oxidative stress, endothelial function and metabolic control in patients with type II diabetes and periodontitis: A randomised controlled clinical trial

Abstract

Background: Periodontitis (PD) and type 2 diabetes (T2D) are characterized by increased mitochondrial oxidative stress production (mtROS), which has been associated with a greater risk of cardiovascular diseases (CVD). Intensive PD treatment (IPT) can significantly improve endothelial function and metabolic control, although the mechanisms remain unclear. We explored whether, in patients with PD and T2D, changes of mtROS are associated with improvement of endothelial function and metabolic control after IPT.

Methods: 51 patients with T2D and PD were enrolled in a single-blind controlled trial and randomised to either intensive (n = 27) or standard (CPT, n = 24) PD treatment. Levels of mtROS in peripheral blood mononuclear cells (PBMC) were measured using a FACS-based assay at baseline and 24 h, 1 week, 2 and 6 months after PD treatment. Inflammatory cytokines, CVD risk factors, metabolic control and endothelial function were assessed at baseline and 6 months after intervention.

Results: After 6 months from PD treatment, the IPT group had lower mtROS (in both the whole PBMC and lymphocytes), circulating levels of HbA1c, glucose, INF-γ, TNF-α (p < 0.05 for all), and improved endothelial function (p < 0.05) compared to the CPT group. There was an association between higher mtROS and lower endothelial function at baseline (r = -0.39; p = 0.01) and, in the IPT group, changes of mtROS were associated with changes of endothelial function (r = 0.41; p < 0.05).

Conclusions: Reduced mtROS is associated with improved endothelial function and accompanied by better metabolic control in patients with T2D and PD. mtROS could represent a novel therapeutic target to prevent CVD in T2D.

Keywords: Diabetes; Endothelial function; Inflammation; Mitochondrial oxidative stress; Periodontitis.

Fig. 1

Changes in mitochondrial reactive oxygen species production (mtROS) production during the study period in A) PBMC, B) Lymphocytes, C) Monocytes. I bars represent SE. mtROS production was significantly lower in PBMC (p < 0.01) and lymphocytes (p < 0.05) at 6 months in the IPT compared to the CPT group.

Fig. 2

A) Flow-mediated dilatation at baseline and 6 months after periodontal therapy. I bars represent SE. At 6 months of treatment, there was a significant difference in FMD between IPT and CPT groups (p < 0.03). B) Nitroglycerin-dependent dilation of the brachial artery in the IPT and CPT groups. I bars represent SE. At 6 months from treatment, no significant difference of the endothelial independent vasodilation was observed between IPT and CPT groups.

Fig. 3

Scatter plot reporting the significant association between changes of mitochondrial reactive oxygen species production (mtROS) in lymphocytes and changes in the flow mediated dilation (FMD) (r = 0.409; p = 0.042).