Glycemic fluctuation exacerbates inflammation and bone loss and alters microbiota profile around implants in diabetic mice with experimental peri-implantitis

Abstract Background The impact of glycemic fluctuation under diabetic condition on peri-implantitis in diabetic patients remains unclear. We hypothesized that glycemic fluctuation has greater adverse effect on experimental peri-implantitis, compared with sustained high blood glucose in diabetes. Results Maxillary left first and second molars of diabetic db/db mice were extracted and were replaced with one dental implant in the healed edentulous space. Glycemic control or fluctuation were managed by constant or interrupted oral administration of rosiglitazone to these mice. Meanwhile, experimental peri-implantitis was induced by ligation around implants. After 14 weeks, inflammatory responses, and peri-implant bone loss, together with oral microbiota profile were analyzed. Diabetic mice with glycemic fluctuation showed greater peri-implant bone loss, inflammatory cell infiltration, and osteoclastogenesis, compared with mice with sustained hyperglycemia. Compared to sustained hyperglycemia, glycemic fluctuation led to further increase in IL-1β, TNFα, RANKL, TLR2/4, IRAK1, and TRAF6 mRNA expression in peri-implant gingival tissues. Both rosiglitazone-induced glycemic control and glycemic fluctuation caused microbiota profile change in diabetic mice compared to that in uncontrolled hyperglycemic mice. Conclusions This study suggests that glycemic fluctuation may aggravate peri-implantitis inflammation and bone loss, which may be associated with a shift in peri-implant microbial profile towards dysbiotic changes and the activation of TLR2/4-IRAK1-TRAF6 signaling