AGEs and Complications Blood Glucose Glycosylated Proteins AGEs

AGEs and Complications Blood Glucose Glycosylated Proteins (AGEs) Monocyte AGE Receptor (RAGE) Secretion of Monokines (cachectin/TNF, IL-1, IGF-1) Mesenchymal Cells Proteinase Production Connective Tissue Breakdown Endothelial Cells Growth Factor Release Proliferation of Cells and Matrix

Diabetes and Periodontitis AGE - enriched gingival tissues Activation of RAGE Macrophage RAGE MP migration & immobilization at AGE rich sites, cytokines (IL-1&6, TNF- ), MMPs Exaggerated response to periodontal pathogens Endothelial RAGE permeability & adhesion molecules Fibroblast RAGE MMPs & Collagen Accelerated destruction of non-mineralized connective tissue and bone in diabetes

Risk and Rate of Progression are Altered by Diabetes Bacterial Products Bacterial Component Host Cells + Prostanoids (PGE) Cytokines (IL-1, IL-6, TNF) Enzymes (MMPs) Pockets and CAL Bone Resorption Tooth Mobility and Loss Connective Tissue Breakdown Host Response Component = Clinical Sequelae Simplified schematic depicting etiologic factors and cascade of events contributing to periodontitis which are altered by the systemic disorder, diabetes

Modifiers in Type 1 Diabetes SALVI et al. , 1998 • High levels of GCF IL-1 & PGE 2 • Monocytic hypersecretory trait – PGE 2 (4. 2 fold) – IL-1 (4. 4 fold) – TNF- (4. 6 fold) • Moderate-Severe >Gingivitis-Mild >Non-Diabetics • Type 1 subjects are at significant risk for periodontitis due to excessive inflammation with equivalent bacterial burden

Diabetes & Periodontitis GENERAL TRENDS • Poor control increases susceptibility – Oral Infections – Periodontitis, Candidiasis, Caries – Not correlated to plaque/calculus levels • Advanced systemic complications – Increases frequency and severity of periodontitis • Aging patient populations – Increases incidence of periodontitis

Other Oral Manifestations • Enlarged parotid glands – alterations in basement membranes • Xerostomia – related to glands and medications • Candidiasis – related to glucose and xerostomia • Burning mouth or tongue • Caries – increased glucose levels in GCF of poorly controlled diabetics