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

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

Risk and Rate of Progression are Altered by Diabetes Pockets and CAL Tooth Mobility Loss Prostanoids (PGE) Cytokines (IL-1,IL-6, TNF) Enzymes (MMPs) Bone Resorption Connective Tissue Breakdown Bacterial Products Host Cells Bacterial Component Clinical Sequelae + Host Response Component = 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 & PGE2 Monocytic hypersecretory trait PGE2 (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