Host Modulation/Periodontal Therapy Effects on Diabetes

描述：（由申请人提供）：在大约1600万美国人中， 患有糖尿病的人中，约有10%患有1型糖尿病。的 这种慢性疾病的并发症，即肾病，视网膜病， 神经病、血管病、伤口愈合受损和牙周炎， 影响糖尿病患者的生活质量。近年来 新的连续治疗，经典的胰岛素治疗，靶向因素知道 在这些长期并发症中发挥作用， 正在进行临床测试。糖尿病患者往往有一个夸张的主机反应， 局部微生物因素导致牙周异常破坏 崩溃此外，牙周感染导致过度 细胞因子（1 L 1、1 L-6和TNF（a））的产生诱导胰岛素抵抗， 降低胰岛素的作用。四环素，包括亚抗菌剂量的 强力霉素（SDD），凭借非抗菌特性可以降低水平 在这些细胞因子和其他因子（基质金属蛋白酶{MMPs}）中， 氧化物[NO]），已知在糖尿病并发症中起作用，包括 牙周炎这些生物学特性使SDD成为一种令人信服的候选药物， 用于糖尿病牙周炎患者。因此，本研究的目的 是研究SDD在糖尿病并发症中的治疗潜力， 例如牙周炎。这一建议的假设是， SDD牙周治疗（与安慰剂相比）可以改善临床和 牙周炎的局部生化指标以及全身生化指标 和指示进展可能性的生理参数，或者 糖尿病长期并发症的严重程度。因此，具体目标 这项建议的目的是使用一个为期9个月的双盲，安慰剂对照试验， 1型糖尿病患者，以确定SDD对以下方面的影响： 非手术牙周治疗; B）口腔微生物区系; c）口腔、血清和 尿中细胞因子（IL-1、IL-6、TNF（a））、MMP和NO的水平; d）血红蛋白A1 c， 血清非空腹葡萄糖和果糖胺;和 蛋白尿。据推测，SDD最初是为改进的 牙周炎的管理，可能是潜在的辅助胰岛素治疗， 改善糖尿病患者的整体管理。

DESCRIPTION: (provided by applicant): Of the approximately 16 million Americans suffering from diabetes mellitus, about 10 percent have Type 1 diabetes. The complication of this chronic disease, i.e. nephropathy, retinopathy, neuropathy, angiopathy, impaired wound healing and periodontitis, significantly, impact the diabetic individuals quality of life. In recent years new adjunctive treatments, to classic insulin therapy, targeting factors know to play a role in these long-term complications have been developed and are being tested clinically. Diabetics tend to have an exaggerated host response to local microbial factors resulting in unusually destructive periodontal breakdown. In addition, periodontal infections resulting in excessive production of cytokines (1L1, 1L-6 and TNF (a)) induce insulin resistance and decrease insulin action. Tetracycline's, including a sub-antimicrobial dose of doxycycline (SDD), by virtue of non-antimicrobial properties can reduce level of these cytokines and other factors (matrix metalloproteinase {MMPs}), nitric oxide [NO]) known to play a role in diabetic complications, including periodontitis. These biological properties make SDD a compelling candidate for use in diabetics with periodontitis. Therefore, the objective of this research is to investigate the therapeutic potential of SDD in diabetic complications, such as periodontitis. The hypothesis of this proposal is that adjunctive periodontal therapy with SDD (compared to placebo) can improve clinical and local biochemical parameters of periodontitis as well as systemic biochemical and physiological parameters indicative of the likelihood of he progression or severity of long-term complications of diabetes. Accordingly, the specific aim of this proposal is to use a 9 month double -blind, placebo-controlled trail of Type 1 diabetics to determine the effect of SDD on: a) the clinical efficacy of non-surgical periodontal therapy; b) the oral microflora; c) oral, serum and urine levels of cytokines (1L-1, 1L6, TNF (a)), MMPs and NO; d) hemoglobin Aic, serum non-fasting glucose and fructosamine; and e) microalbuminuria and proteinuria. It is postulated that SDD, developed initially for the improved management of periodontitis, may be potential adjunct to insulin therapy in diabetic patients for the improved overall management of diabetes.