Host Modulation/Periodontal Therapy Effects on Diabetes

描述：(申请人提供)：在大约1600万患有糖尿病的美国人中，约10%患有1型糖尿病。这个 这种慢性疾病的并发症，即肾病、视网膜病变、 神经病、血管病、伤口愈合障碍和牙周炎， 显著影响糖尿病患者的生活质量。近几年来 新的辅助治疗，对经典的胰岛素治疗，靶向因子知道 在这些长期并发症中扮演的角色已经被开发出来并正在 正在接受临床测试。糖尿病患者往往有夸大的宿主反应 导致牙周异常破坏的局部微生物因素 崩溃了。此外，牙周感染导致过度 产生细胞因子(1L1、1L-6和肿瘤坏死因子(A))可诱导胰岛素抵抗和 减少胰岛素的作用。四环素类药物，包括亚抗菌剂量的 强力霉素(SDD)，凭借其非抗菌特性，可降低体内 在这些细胞因子和其他因子(基质金属蛋白酶)中， 氧化物[NO])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成为令人信服的候选 用于患有牙周炎的糖尿病患者。因此，这项研究的目的是 是为了研究SDD在糖尿病并发症中的治疗潜力， 比如牙周炎。这一提议的假设是，附加性 使用SDD进行牙周治疗(与安慰剂相比)可以改善临床和 牙周炎局部生化指标及全身生化指标 和生理参数指示进展的可能性或 糖尿病长期并发症的严重程度。因此，具体目标是 这项建议的目的是使用为期9个月的双盲、安慰剂对照试验 确定SDD对1型糖尿病患者的影响：a)临床疗效 非手术牙周治疗；b)口腔微生物区系；c)口腔、血清和 尿液细胞因子(1L-1、1L6、肿瘤坏死因子(A))、基质金属蛋白酶(MMPs)和一氧化氮(NO；d)、血红蛋白(AIC)、 血清非空腹血糖和果糖胺；以及e)微量白蛋白尿和 蛋白尿。据推测，SDD最初是为改进的 牙周炎的治疗，可能是胰岛素治疗的潜在辅助手段 为提高糖尿病患者的整体管理水平。

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.