3.1.1. Diabetes

The most important complication of periodontal disease is diabetes, and the risk of diabetes mellitus is increased by periodontal disease, suggesting that this association is bidirectional. In fact, the prevalence of diabetes is higher in patients with periodontal disease than in those without periodontitis [53]. Furthermore, the Hisayama study in Japan showed that patients who developed glucose intolerance were more likely to have periodontal disease than the group that did not develop glucose intolerance [54]. Diabetic nephropathy with overt proteinuria occurs as a result of long-term diabetes, but diabetes patients with periodontal disease have a higher risk of cardiovascular disease

compared with patients without periodontal disease [55]. Therefore, diabetic nephropathy caused by periodontal disease shortens the clinical course of ESRD [56]. With regard to the molecular mechanisms involved, the inflammatory cytokines IL-1 and IL-6, TNFα; fibrotic growth factors TGF-β and CTGF; and oxidative stress have all been implicated in the original pathogenesis of diabetic nephropathy [57]. There is a close relationship between diabetes and periodontal disease and glycemic control is crucial, not only for kidney function, but also periodontal disease. Leukocyte function is poorly controlled in diabetic patients and this may worsen and exacerbate periodontal disease [58]. The e ffects of periodontal disease on diabetic nephropathy vary depended upon the patients' condition. Thus, diabetic patients with periodontal disease should be treated intensively both for glycemic control and periodontal diseases.
