The present narrative review examines the scientific evidence of the biological mechanisms that may link periodontitis and diabetes, as a source of comorbidity. Publications regarding periodontitis and diabetes, in human, animals, and in vitro were screened for their relevance. Periodontal microbiome studies indicate a possible association between altered glucose metabolism in prediabetes and diabetes and changes in the periodontal microbiome. Coinciding with this, hyperglycemia enhances expression of pathogen receptors, which enhance host response to the dysbiotic microbiome. Hyperglycemia also promotes pro-inflammatory response independently or via the advanced glycation end product/receptor for advanced glycation end product pathway. These processes excite cellular tissue destruction functions, which further enhance pro-inflammatory cytokines expression and alteration in the RANKL/osteoprotegerin ratio, promoting formation and activation of osteoclasts. The evidence supports the role of several pathogenic mechanisms in the path of true causal comorbidity between poorly controlled diabetes and periodontitis. However, further research is needed to better understand these mechanisms and to explore other mechanisms.
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