# Impact of Peri-Implant Inflammation on Metabolic Syndrome Factors: A Systematic Review
## 4 Discussion  
To the best of the authors' knowledge, this is the first systematic review assessing the potential impact of peri-implantitis on MetS or its components. There is some suggestion, based on the included studies, that peri-implantitis is associated with altered metabolic factors of MetS, including serum lipid profile and HbA1c levels. However, based on the cross-sectional design and the heterogeneity of the included studies, there is not enough evidence to support any clinical implications. The relationship between MetS and peri-implantitis is very complex. Multiple studies have revealed that components of MetS are linked to the risk of developing peri-implantitis [37; 51]. On the other hand, some studies suggest that chronic inflammation may represent as a triggering factor in the initiation of MetS [52], underlining a bilateral association between MetS and oral chronic inflammation. As an analogue of peri-implantitis, periodontitis is reported to influence systemic conditions, affecting both inflammatory mediators [53; 54] and metabolic indicators [55]. Therefore, as a chronic inflammatory disease in the oral cavity, peri-implantitis, which also influences systemic levels of pro-inflammatory cytokines, is intuitively inferred to have a potential impact on MetS and its components. Furthermore, there is solid evidence provided by a systematic review suggesting that hyperglycemia and peri-implantitis are associated [21]. The risk of developing peri-implantitis in hyperglycemia subjects is 1.21- and 2.46- fold statistically significantly higher than that in normoglycemia subjects. In addition, obesity is found to be associated with elevated pro-inflammatory cytokines and worsened clinical parameters in subjects with peri-implantitis [56; 57]. The mechanism behind the association between peri-implantitis and hyperglycemia/obesity lies in the reduction of vascular supply caused by microan-gioopathies, cellular dysfunction due to toxic microbial metabolites, and decreased immune robustness towards oral pathogens [26]. To this point, a reasonable inference can be made that there might be a bi-directional correlation between peri-implantitis and MetS components, linked by systemic inflammatory burdens. However, it is acknowledged that there is currently a gap of knowledge on whether the presence of peri-implantitis is associated with degree of hyperglycemia/dyslipidemia or severity of obesity. In this systematic review, we found five related studies to address this question, all of which were cross-sectional in nature. [PERSON]'s results [47] showed that peri-implantitis is associated with significantly higher levels of HbA1c both in T2 DM and non-T2 DM subjects. Nonetheless, all participants included in this study were males, which consequently led to potential bias given the hormonal differences, and the evidence that gender has been identified as a predictive factor for peri-implant bone levels [58]. Further, the statistical analysis for HbA1c level was not adjusted by other confounding factors such as age, history of periodontitis, or smoking habits. The observation of significantly higher HbA1c levels confirmed the link between hyperglycemia and peri-implantitis, but the cause-and-effect relationship needs to be further confirmed by longitudinal cohort studies. In contrast, [PERSON]'s study [48] reported that blood glucose was not significantly different between peri-implantitis and controls. This is probably due to the relatively small sample size in this study along with the inclusion of other confounding factors such as history of periodontitis and current smokers, both of which can have an impact on glycemic control [59; 60]. The primary finding of [PERSON]'s study was that peri-implantitis is associated with dyslipidemia, in agreement with [PERSON]'s study [12]. However, it should be noted that the findings of these two studies were not completely consistent. Among the four indicators for lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides),[PERSON] et al.