Host Modulation/Periodontal Therapy Effects on Diabetes

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.