Metformin as an add-on to insulin improves periodontal response during orthodontic tooth movement in type 1 diabetic rats

Abstract

BACKGROUND: Type 1 diabetes (T1D) is associated with delayed tissue healing and bone loss. Periodontal tissues during tooth movement (OTM) in T1D and under diabetic treatment are poorly understood. We aimed to study the effect of metformin as an add-on to insulin therapy on periodontal structures during OTM in T1D rats. METHODS: Rats were divided into normoglycemic (NG, n = 20) and streptozotocin-induced diabetic groups that were untreated (T1D, n = 20), treated with insulin (I-T1D, n = 20), or treated with insulin plus metformin (IM-T1D, n = 20). After 7 days of treatment, the first right upper molar (M1) was moved mesially. At days 0, 3, 7 and 14, the pattern of OTM and the periodontal tissues were analyzed by micro-CT, histomorphometry, and immunohistochemistry for TRAP. RESULTS: In T1D, major osteoclastogenic activity and bone loss versus other groups were confirmed by a greater TRAP-positive cell number and reabsorption surface on both the pressure and tension sides for 14 days (p < 0.01). Additionally, we observed low bone volume density. Metformin plus insulin resulted in a daily insulin dose reduction and major glycemic control versus I-T1D. Although no significant differences were observed between I-T1D and IM-T1D, the tooth displacement and inclination, periodontal ligament thickness, and alveolar bone density on the pressure side in IM-T1D were similar to that of NG (p > 0.05). CONCLUSION: Antidiabetic treatment reduces severe periodontal damage during applied orthodontic force in T1D untreated rats. Metformin as an add-on to insulin therapy resulted in glycemic control and a periodontal tissue response to orthodontic forces that was similar to that of normoglycemic rats.