Mechanisms linking periodontitis and diabetes

Background + Aims

• The Wnt/β-catenin signalling pathway helps regulate the development and survival of osteoblasts, the cells responsible for forming bone.
• Sclerostin (SOST) and Dickkopf-1 (DKK1) inhibit this pathway, potentially shifting the balance away from bone formation and contributing to periodontal breakdown.
• This study aimed to:
  • Compare local and circulating levels of sclerostin and DKK1 in people with periodontitis, with and without type 2 diabetes and smoking, and examine their relationships with inflammatory markers, bone-regulating proteins and periodontal bacteria.

Materials + Methods

• This cross-sectional study included 114 adults aged 34–70, all with generalised chronic periodontitis:
  • 30 non-diabetic non-smokers
  • 33 non-smokers with diabetes
  • 26 smokers without diabetes
  • 25 smokers with diabetes.
• Participants with diabetes had been diagnosed for at least 3-years. Smokers reported smoking ≥10 cigarettes daily for 10-years.
• Full-mouth examinations assessed plaque, bleeding on probing, pocket depth and clinical attachment level.
• Gingival biopsies and subgingival plaque samples were collected from 2 teeth per participant requiring extraction because of advanced periodontitis.
• Blood samples were also obtained.
• Laboratory testing measured protein levels and gene expression, indicating how actively cells were producing instructions for these proteins.
• Additional markers included inflammatory cytokines and RANKL and osteoprotegerin (OPG).
  • RANKL promotes bone-resorbing cell formation, while OPG limits this signal.

Results

• Gingival DKK1 protein levels were significantly higher in all three groups with diabetes and/or smoking than in non-diabetic non-smokers.
• Gingival sclerostin protein levels were significantly higher in both smoking groups. In non-smokers with diabetes, sclerostin gene expression and serum protein levels were elevated, but gingival protein levels were not significantly increased.
• Non-smokers with diabetes had significantly higher gingival gene expression of both DKK1 and sclerostin than controls.
• Gingival IL-6 and TNF-α, inflammatory signalling proteins, were elevated in all groups with diabetes and/or smoking.
• DKK1 and sclerostin gene expression correlated positively in the control and both diabetes groups. Associations with other inflammatory and bone-regulating markers were particularly evident in smokers with diabetes.
• Relationships between these inhibitors and periodontal bacteria occurred mainly in the diabetes groups, with both positive and negative associations depending on the organism and smoking status.
• Clinical periodontal measurements did not differ significantly between groups, indicating that the molecular differences were observed in groups with broadly comparable disease severity.

Limitations