Study of Pathways in the Link Between Type 2 Diabetes and Periodontitis

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ABSTRACT: Lipid lowering agents (LLA), such as statins, are known to have pleiotropic anti-inflammatory effects and have recently been seen to reduce the occurrence of periodontal tissue destruction. However, no study has thoroughly assessed the potential role of LLA use in reducing inflammatory responses in periodontal disease (PD) development, especially among type 2 diabetic (T2D) individuals in whom hyperinflammatory condition is present. We propose to assess the anti-inflammatory effects of LLA, through activation or up-regulation of peroxisome proliferator-activated receptors- alpha (PPAR-α) and/or PPAR-ɣ, on the occurrence of PD among overweight or obese T2D individuals. We hypothesize that diabetic individuals taking LLA, such as statins, will have high systemic levels of PPAR-ɣ, which, in turn, may lower local and systemic inflammatory responses to PD pathogens thereby reducing the occurrence of PD compared with adult diabetic individuals who do not take statins. More specifically, we will assess whether LLA use, especially statins, reduces periodontal measurements, determined by probing pocket depth (PPD), clinical attachment loss (CAL) and bleeding on probing (BOP), among diabetic adults. We will also evaluate whether the trends in the effects of statins on these periodontal destructions are mediated by the reduction of both gingival crevicular fluid (GCF) and serum levels of IL-1β, IL-17, and TNF-α, and GCF levels of bone related factors, such as OPG and RANKL. Furthermore, we will explore in our secondary aim whether the anti-inflammatory effects of statins are associated with up-regulation of PPAR-ɣ expression. We expect that the mRNA expression levels of PPAR-ɣ among diabetic individuals who take statins would be higher than those in controls without the medications. The proposed study will retrospectively recruit a total of 260 diabetic adults aged 40 to 65 years, divided into two groups: 130 adults taking statins and 130 adults not taking the medications. Detailed information of statin use, type, frequency, dosage and duration use will be collected to assess statin exposure. Periodontal status of each participant will be assessed as a main outcome and the GCF and serum levels of IL-1β, IL-17, and TNF-α as well as GCF levels of OPG and RANKL as secondary outcomes. For the secondary aim, a total of 40 participants (20 diabetic individuals with statins and 20 diabetic individuals without statins) matched by age, gender, BMI, and smoking status will be drawn from the total population (N=260) to assess the potential effect of statins on the up-regulation of PPAR-ɣ expression to investigate its influence on PD occurrence among T2D individuals. Findings from this retrospective study will be highly relevant for public health given the high prevalence of PD among T2D patients, and could be used for developing prevention or support possible local statins delivery for PD therapeutic strategies in the future.