Novel Link Between Xerostomia and Tooth Decay in Diabetic Model

Insulin-dependent type-1 diabetes mellitus (DM) and oral diseases are closely interrelated. Poor metabolic control in diabetics is associated with a high risk of gingivitis, periodontitis and tooth loss. Salivary flow declines in diabetics and patients suffer from xerostomia. Reduced saliva predisposes to enamel hypomineralization and caries formation; however, the mechanisms that initiate and lead to progression of tooth decay and periodontitis in type-1 DM have not been explored. To address this issue, we analyzed tooth morphology in Akita-/- mice that harbor a point mutation in the Ins2 insulin gene which leads to insulin deficiency and hyperglycemia. Objective: To characterize the tooth phenotype in Akita-/- mice and determine whether hyperglycemia and hyposalivation contribute to dental defects. Methods: Mandibles from Akita-/- and wild type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin and ameloblastin expression. Mice were injected with pilocarpine to assess saliva production. The effect of high glucose on cultured MD10-F2 pulp cells was also analyzed. Results: Akita-/-mice at 6 weeks showed chalky white incisors that correlated with marked hyperglycemia and impaired saliva production. MicroCT of Akita-/- teeth revealed excessive enamel wearing and hypomineralization; immunostaining for amelogenin and ameloblastin was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in pulp horns and progressed to pulp necrosis and periodontitis. Akita+/-mice also developed dental defects. High glucose levels inhibited MD10-F2 cell proliferation/differentiation. Conclusions: Results provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type-1-DM leads to decreased enamel mineralization/matrix proteins and predisposes to excessive wearing and decay. Importantly, hyperglycemia adversely affects enamel matrix proteins and pulp repair. Early detection and treatment of hyperglycemia and hyposalivation may provide a useful strategy for preventing dental complications of diabetes and promoting oral health in this population.��