Study of Pathways in the link between Type 2 Diabetes and Periodontitis

 描述（由申请人提供）：已知降脂剂（LLA），如他汀类药物具有多效抗炎作用，最近发现可减少牙周组织破坏的发生。然而，没有研究彻底评估了LLA使用在减少牙周病（PD）发展中的炎症反应方面的潜在作用，特别是在存在高度炎症的2型糖尿病（T2 D）个体中。我们建议通过激活或上调过氧化物酶体增殖物激活受体-α（PPAR-α）和/或PPAR-γ，评估LLA对超重或肥胖T2 D个体发生PD的抗炎作用。我们假设，与未服用他汀类药物的成年糖尿病个体相比，服用LLA（如他汀类药物）的糖尿病个体将具有高的全身性PPAR-γ水平，这反过来可能降低对PD病原体的局部和全身炎症反应，从而减少PD的发生。更具体地说，我们将评估LLA的使用，特别是他汀类药物，是否减少牙周测量，通过探测袋深度（PPD），临床附着丧失（CAL）和探测出血（BOP），在糖尿病成人。我们还将评估他汀类药物对这些牙周破坏的影响趋势是否通过减少龈沟液（GCF）和血清IL-1 β、IL-17和TNF-α水平以及GCF中骨相关因子（如OPG和RANKL）水平介导。此外，我们将在我们的次要目标中探索他汀类药物的抗炎作用是否与PPAR-γ表达的上调相关。我们预计，服用他汀类药物的糖尿病患者的PPAR-γ mRNA表达水平将高于未服用药物的对照组。 这项研究将回顾性招募260名40至65岁的糖尿病成年人，分为两组：130名服用他汀类药物的成年人和130名未服用药物的成年人。将收集他汀类药物使用、类型、频率、剂量和持续时间的详细信息，以评估他汀类药物暴露。将评估每名受试者的牙周病状态作为主要结局，GCF和IL-1 β、IL-17和TNF-α的血清水平以及OPG和RANKL的GCF水平作为次要结局。对于次要目的，将从总人群（N=260）中抽取年龄、性别、BMI和吸烟状态匹配的共40例受试者（20例接受他汀类药物治疗的糖尿病患者和20例未接受他汀类药物治疗的糖尿病患者），以评估他汀类药物对PPAR-γ表达上调的潜在影响，从而研究其对T2 D患者PD发生率的影响。鉴于T2 D患者中PD的高患病率，这项回顾性研究的结果将与公共卫生高度相关，并可用于开发预防或支持未来可能的PD治疗策略的局部他汀类药物给药。

 DESCRIPTION (provided by applicant): 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-γ, 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-γ 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-1ß, IL-17, and TNF-a, 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-γ expression. We expect that the mRNA expression levels of PPAR-γ 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-1ß, IL-17, and TNF-a 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-γ 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.