The peroxisome proliferator-activated receptor gamma (PPARG) gene encodes a transcription factor involved in the regulation of complex metabolic and inflammatory diseases. We investigated whether single nucleotide polymorphisms (SNPs) and haplotypes of the PPARG gene could contribute with susceptibility to develop periodontitis alone or together with type 2 diabetes mellitus (T2DM). Moreover, we evaluated the gene–phenotype association by assessing the subjects’ biochemical and periodontal parameters, and the expression of PPARG and other immune response–related genes. We examined 345 subjects with a healthy periodontium and without T2DM, 349 subjects with moderate or severe periodontitis but without T2DM, and 202 subjects with moderate or severe periodontitis and T2DM. PPARG SNPs rs12495364, rs1801282, rs1373640, and rs1151999 were investigated. Multiple logistic regressions adjusted for age, sex, and smoking status showed that individuals carrying rs1151999-GG had a 64% lower chance of developing periodontitis together with T2DM. The CCGT haplotype increased the risk of developing periodontitis together with T2DM. The rs1151999-GG and rs12495364-TC were associated with reduced risk of obesity, periodontitis, elevated triglycerides, and elevated glycated hemoglobin, but there was no association with gene expression. Polymorphisms of the PPARG gene were associated with developing periodontitis together with T2DM, and with obesity, lipid, glycemic, and periodontal characteristics.

This study aimed to develop and validate a dual murine model integrating a high-fat diet (HFD) and a single streptozotocin (STZ) dose to induce diabetes mellitus (DM), alongside periodontitis (Perio) induced by ligature placement and oral inoculation with Porphyromonas gingivalis (P. gingivalis). The goal was to mimic human pathological conditions, creating a physiologically relevant environment to study the interplay between DM and Perio. A total of 128 six-week-old male C57BL/6J mice were randomly divided into four groups: Control, DM, Perio, and DM-P. DM was induced by HFD and STZ injection, and Perio by ligature placement and P. gingivalis infection. Evaluations occurred at baseline and days 7, 14, and 21. Alveolar bone loss was assessed by micro-computed tomography, and inflammation was examined histologically. DM mice showed elevated glucose levels and insulin resistance. Perio and DM-P groups experienced significant bone loss compared with Control and DM groups. The morphometric analysis revealed abundant inflammatory cells and reduced collagen fibers in Perio and DM-P groups, especially at day 7. This dual murine model successfully replicated the key features of DM and Perio, maintaining overall health of the animals, and good tolerability by those subjects to the stress of both interventional procedures.

This study aimed to integrate current evidence on Interleukin-7 (IL-7) in the context of Type 2 Diabetes Mellitus (T2DM), Dyslipidemia (Dysl), and Periodontitis (Perio). We performed a meta-analysis on IL-7 protein levels in individuals with these conditions, and we investigated gene and protein IL-7 levels in 217 participants from two independent cohorts, distributed into: (i) poorly-controlled T2DM, Dysl, and Perio (T2DMpoor_Dysl_P), (ii) well-controlled T2DM, Dysl, and Perio (T2DMwell_Dysl_P), (iii) Dysl and Perio (Dysl_P), (iv) Periodontitis (Perio), and (v) Healthy individuals (Control). Participants underwent physical, biochemical, and periodontal examinations. IL7 gene expression in peripheral blood mononuclear cells was quantified by RT-qPCR, and IL-7 protein levels were measured in gingival crevicular fluid (GCF), plasma, and saliva. Meta-analysis of 454 participants showed no statistical differences in IL-7 protein levels in GCF or plasma/serum, with substantial heterogeneity among studies. Our two independent cohorts demonstrated that IL7 mRNA was higher in T2DMwell_Dysl_P than in T2DMpoor_Dysl_P subjects. In cohort 1, IL-7 protein levels were higher in GCF from healthy sites, similar among groups in diseased sites, and in plasma. Saliva in cohort 2 showed low IL-7 levels in all groups. Significant inverse correlations were found between IL-7 protein and anthropometric measures, and worsened periodontal parameters. These findings and the IL7 mRNA expression replicated across both cohorts lead to conclude that IL-7 is a potential candidate biomarker of immunometabolic and periodontal status, despite its variance in biological compartments. Further clinically similar studies enrolling larger populations are required to confirm these results and assess the biological and clinical relevance of IL-7.