Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice

Abstract

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 progressive hyperglycemia. Mandibles from Akita −/− and wild-type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin (Amel) and ameloblastin (Ambn) expression. Mice were injected with pilocarpine to assess saliva production. As hyperglycemia may alter pulp repair, the effect of high glucose levels on the proliferation/differentiation of cultured MD10-F2 pulp cells was also analyzed. Results showed that Akita −/− mice at 6 weeks of age 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 Amel and Ambn was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in the coronal pulp and progressed to pulp necrosis and periapical periodontitis. High levels of glucose also inhibited MD10-F2 cell proliferation and differentiation. Our findings provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type1 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 the dental complications of diabetes and promoting oral health in this population.

Relationship of salivary flow of diabetic patients

“…Even if the association between these variables did not show significant results, it is suggested a relationship with dysfunction of salivary secretion resulting from this situation. Of the sample, 54.5% exhibited decreased salivary flow, even that the association of dry mouth and saliva amount (p=0.076) and stimulated saliva (p=0,067) did not show statistically differences, corroborating the literature [4,7,11,17,19,23,26]. Although further studies with larger samples should be conducted in the search for meaningful results, the relationship between the dentist and doctor is necessary, and the medical history of the patient is essential for diagnosis and best treatment in situations of hyposalivation and xerostomia.…”

Update knowledge of dry mouth- A guideline for dentists

“…It is, however, common in those suffering from type 1,2 diabetes (27)(28). Dry mouth may be caused as a side effect of medication that is being consumed to keep the diabetes in control.…”

Determining the Role of Sost and Sostdc1 During Fracture Healing

“…Akita mice are hyperglycemic with a bone loss skeletal phenotype being more severe in male offsprings of diabetic fathers [166]. Previous studies also revealed that Akita mice have decreased anabolic response in bone formation upon mechanical loading, revealing altered osteoblast response in bone reponse to loading [167], as well as having chalky white incisors with decreased enamel mineralization [168]. The Akita mice have an osteoporotic bone phenotype similar to patients with T1DM, and in comparison have a less severe osteoporotic bone phenotype compared to the drug induced diabetic mouse model, Streptozotocin (STZ) mice [52].…”