Fogorvosi szemle, 2007 (100. évfolyam, 1-6. szám)
2007-10-01 / 5. szám
252 FOGORVOSI SZEMLE ■ 100. évf. 5. sz. 2007. Vascular complications are classically associated both with DM2 and the earlier phases of glucose metabolism disorders [31], AGE deposition increases the capillary basement membrane thickness resulting in a serious narrowing of the lumen and impairs the exchange of oxygen and metabolic waste products through the capillary wall. Moreover, AGEs provoke also macrovascular complications. They increase the cross-link of collagen and the highly stable collagen macromolecules are resistant to normal enzymatic degradation and tissue turnover [38]. AGE-modified collagen deposits thicken the vessel wall and covalently cross-link with circulating low-density lipoprotein, contributing to development of atherosclerosis. The cumulative effect of these vascular alterations is a progressive narrowing of the vessel lumen and a decreased perfusion of the affected tissue. Hypoxia is also advantageous for tumor cell multiplication as nonoxidative steps in the anabolic pathways characterize their metabolism [20]. The highly stable collagen accumulates also in the basement membrane of the epithelium and alters the normal homeostatic transport. Defective transport of oxygen and other metabolites is advantageous also for malignant transformation. It is a well-known fact that collagenase production is increased in DM, which is harmful for periodontal integrity and wound healing [35]. Chemically modified tetracyclines, which have no antibacterial effect whereas, have been shown to significantly decrease collagenase production proved to be effective against gingival inflammation in DM cases. Chemically modified tetracyclines have potential benefits in inhibition of onset and progression of gingivitis and periodontitis in patients with DM. Excessive collagenase activity in diabetic tissues results in enhanced permeability of the extracellular matrix and increased degradation of newly formed collagen, which may provoke the local spread and metastatic activity of tumors [9], Correlations of inflammatory and immunologic alterations in DM2 and OC The altered host immunologic and inflammatory response to the bacterial challenge in patients with DM may be a possible explanation for the increased prevalence and severity of periodontitis and further pathologic processes. AGEs have major effects also at cellular level. A receptor for AGEs known as RAGE (receptor for AGE) has been identified on the surface of many cell types (endothelial cells, smooth muscle cells, monocytes/ macrophages, etc.) [52]. Uncontrolled hyperglycemia increases the RAGE receptor expression and promotes the AGE-RAGE interaction, which are newly recognized factors regulating cancer cell invasion [5]. RAGE expression appears to be closely associated with the invasiveness and metastatic capacity of OC. AGE-RAGE interactions provoke thorough changes on monocyte/macrophage membranes and induce enhanced cellular oxidative stress and activate transcription factors. These signals alter the monocyte/macrophage phenotype and result in increased production of inflammatory cytokines, such as interleukin-1 (IL-1), tumor necrosis factor-a (TNF-a) and growth factors (IGFs and platelet-derived growth factors) [62], Cytokine and growth factor accumulation may contribute not only to the chronic inflammatory processes but also to the development of malignancies [34, 39, 59]. The polymorphonuclear leukocytes play also a major role in maintenance of periodontal health. Numerous studies have shown a reduction in leukocyte function, including chemotaxis, adherence and phagocytosis in DM [33]. Diminished polymorphonuclear leukocyte function and the persistence of bacterial challenge may then be met by an elevated monocyte/macrophage response, which results in increased tissue destruction and tumor risk. Insulin resistance and oral diseases DM2 has long been considered to play thorough influence on intraoral structures. It may seriously alter the mucosal health, integrity of the periodontal tissues, wound healing and bone turnover rate [44]. Xerostomia and degenerative parotid enlargement may occur in patients with DM, and they are usually related to the degree of glycémie control [54]. Epithelial atrophy affects mainly the lower lip and the tongue (atrophic cheilitis and glossitis). DM2 is a crucial risk factor of various intraoral inflammatory lesions. Fungal infections, first of all candidiasis may be prevalent on the vulnerable dry mucosal surfaces. Multivariate regression analysis revealed the presence of Candida albicans hyphae to be significantly related to poor glycémie control [17]. Literary data support the role of chronic hypertrophic Candida albicans infection in development of oral precancerous lesions. Periodontal inflammatory diseases (gingivitis, periodontitis) are also traditional symptoms of uncontrolled DM [35]. Correlations between periodontal diseases and DM2 seem to be fairly complex and are depending on the variability in diagnostic parameters assessed to describe the clinical condition. Some studies could not find specific relationship between periodontal parameters and duration of diabetes, presence of other diabetic complications, or degree of diabetic control. This suggests that not only the extent of hyperglycemia and bacterial invasion define the periodontal state of patients with DM but other important players may also be supposed. Considering the well-known oral manifestations of
