Evidence Linking PPARG Genetic Variants with Periodontitis and Type 2 Diabetes Mellitus in a Brazilian Population.

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.

Genetic polymorphisms in the Interleukins IL1B, IL4, and IL6 are associated with concomitant periodontitis and type 2 diabetes mellitus in Brazilian patients.

OBJECTIVE: To assess whether single nucleotide polymorphisms (SNPs) in the IL10, IL1A, IL1B, IL4, TNFA, IL6, OPG, RANK, and RANKL genes, "classically" related with periodontitis, could be associated with susceptibility to T2DM, and also with both diseases concomitantly. BACKGROUND: There are common pathogenic mechanisms in type 2 diabetes mellitus (T2DM) and periodontitis, but the knowledge of the genetic aspect of this is limited. In patients affected by concomitant T2DM and periodontitis, whose incidence is increasing, there is scarce information regarding the gene-phenotype association, including whether there are genes able to influence both diseases as comorbidities. METHODS: Periodontal clinical parameters and biochemical profile (Insulin, Fasting Glycemia, HbA1c, Triglycerides, Total Cholesterol, HDL-cholesterol, and LDL-cholesterol) data were obtained from 894 individuals divided into following three groups: Healthy (H; n = 347), Periodontitis (P; n = 348), and Periodontitis + T2DM (P + T2DM; n = 199). DNA from oral epithelial cells was collected for genotyping. Associations between SNPs and pathologies were tested by multiple logistic regression models, adjusting for age, sex, and smoking habits. We also investigated whether there are sex or smoking effects of each SNP in these phenotypes. RESULTS: The rs1143634-GA (IL1B) SNP showed significantly less likely to develop P + T2DM for all population and mainly for women (adjusted OR = 0.37, 95% CI = 0.16-0.88), while women carrying the rs224320 CT (IL4) were more susceptible to develop P + T2DM (adjusted OR = 1.81, 95% CI = 1.04-3.15). Men carrying the rs1800795-CC (IL6) genotype were less likely to develop T2DM (adjusted OR = 0.12, 95% CI = 0.02-0.70, P = .01). CONCLUSIONS: Some SNPs in the IL1B, IL4, and IL6 genes demonstrated sex-influenced association with concomitant periodontitis and T2DM, increasing the evidence of a common genetic component between these diseases and contributing with the understanding of their common pathogenic mechanisms.

Association of active oxygen-releasing gel and photodynamic therapy in the treatment of residual periodontal pockets in type 2 diabetic patients: A randomized controlled clinical study.

BACKGROUND: The aim of this study was to evaluate the effect of active oxygen-releasing gel as an adjuvant, with and without antimicrobial photodynamic therapy (aPDT), in the treatment of residual pockets in periodontal patients with type 2 diabetes mellitus (DM2). METHODS: Patients with residual pockets with probing depth (PD) ≥4 mm and bleeding on probing (BOP) were divided into the following groups: SI (n = 17)-subgingival instrumentation in a single session; BM (n = 17)-SI followed by local application of active oxygen-releasing gel inside the periodontal pocket for 3 min; BM + aPDT (n = 17)-SI followed by application of BM for 3 min and pocket irrigation with methylene blue, and 660-nm diode laser irradiation at 100 mW for 50 s. The periodontal clinical parameters, serum levels of glycated hemoglobin, and immunological analysis of crevicular fluid were evaluated. All data were submitted to statistical analysis (α = 5%). RESULTS: A significant reduction in BOP was verified at 90 and 180 days in the BM + aPDT group. The percentage of sites with PD ≥ 4 mm was significantly reduced at 90 days in BM + aPDT and BM, whereas after 180 days only BM showed a significant reduction. In the BM + aPDT group, there was a significant reduction in tumor necrosis factor α levels at 90 days. There were no differences between the treatments. CONCLUSION: The use of adjuvant active oxygen-releasing gel, with or without aPDT, resulted in the same clinical benefits as SI in the treatment of residual pockets in poorly controlled DM2 patients.

Food selectivity and neophobia in children with autism spectrum disorder and neurotypical development: a systematic review.

CONTEXT: Individuals with autism spectrum disorder (ASD) have common eating problems, including food refusal, dietary restrictions, and behavioral problems during eating. OBJECTIVE: The aim of this systematic review was to find more clear evidence on the relationship between food selectivity or food neophobia (FN) and ASD in children up to age 14 years. The PECO-based question was: Are food selectivity and FN behaviors more prevalent in children with ASD than in children with neurotypical development (NTD)?, in which the P is children, E is ASD, C is children with NTD, and O is food selectivity and FN. DATA SOURCES: Clinical studies in the databases PubMed, Embase and Web of Science, comparing children with ASD and those with NTD, were reviewed from October 1966 to October 2021. STUDY SELECTION AND DATA EXTRACTION: A total of 122 studies were analyzed for summary reading, and only 17 of these were included in the descriptive qualitative analysis. In 9 studies, the analysis of food selectivity was performed via a questionnaire. RESULTS: The results showed that children with ASD are more selective than those with NTD. Four studies evaluated FN through scales; however, only 2 found higher levels of FN in the ASD group than in children with NTD. The sensory profile was measured using questionnaires in 9 studies, and we found that altered sensory processing is more common in children with ASD. CONCLUSION: Children with ASD present greater food selectivity than children with NTD. However, the occurrence of FN was higher in only 50% in which FN was investigated, which points to a need for studies that compare FN between siblings with ASD and those with NTD in the same family nucleus. In addition, atypical oral sensitivity seems to be a sensory characteristic most related to eating disorders. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021247880.

Polymorphisms in risk genes of type 2 diabetes mellitus could be also markers of susceptibility to periodontitis.

OBJECTIVES: This study aimed to investigate polymorphisms in genes considered molecular biomarkers of type 2 diabetes mellitus (T2DM) to assess whether they are associated with periodontitis, and relating them to the periodontal status, glycemic and lipid profile of the subjects. DESIGN: We investigated individuals who underwent complete periodontal examination and biochemical evaluation. We categorized them into three groups: (i) periodontitis with T2DM (Periodontitis+T2DM group, n = 206); (ii) periodontitis without T2DM (Periodontitis group, n = 346); and (iii) healthy individuals without Periodontitis or T2DM (Healthy group, n = 345). We investigated three single nucleotide polymorphisms (SNPs) for AGER, RBMS1 and VEGFA genes. We applied multivariate logistic and multiple linear regression models for all groups and stratified the subjects by sex and smoking habits. RESULTS: Compared with RBMS1-rs7593730-CC+CT genotype carriers, RBMS1-rs7593730-TT carriers were more susceptible to periodontitis [odds ratio (OR) = 2.29; 95% confidence interval (CI) = 1.04-5.01; P-value = 0.033]. Among AGER-rs184003-CC carriers, never smokers had reduced risks of periodontitis and Periodontitis+T2DM than ever smokers. For either RBMS1-rs7593730-CC or VEGFA-rs9472138-CC carriers, never smokers had less susceptibility to develop periodontitis than ever smokers. Compared with AGER-rs184003-CC carriers, AGER-rs184003-AA carriers presented fewer remaining teeth. VEGFA-rs9472138-TT carriers showed a lower percentage of sites with characteristics of active periodontal disease (bleeding on pocket probing and interproximal clinical attachment level) compared with VEGFA-rs9472138-CC carriers. CONCLUSIONS: In the studied population, AGER rs184003, RBMS1 rs7593730, and VEGFA rs9472138, which are considered genetic markers for T2DM, were associated with periodontitis without T2DM or periodontitis together with T2DM.

Polymorphisms in Genes of Lipid Metabolism Are Associated with Type 2 Diabetes Mellitus and Periodontitis, as Comorbidities, and with the Subjects' Periodontal, Glycemic, and Lipid Profiles.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and periodontitis (P) commonly occur as comorbidities, but the commonalities in the genetic makeup of affected individuals is largely unknown. Since dyslipidemia is a frequent condition in these individuals, we investigate the association of genomic variations in genes involved in lipid metabolism with periodontal, glycemic, lipid profiles, and the association with periodontitis and T2DM (as comorbidities). METHODS: Based on clinical periodontal examination and biochemical evaluation, 893 subjects were divided into T2DM+P (T2DM subjects also affected by periodontitis, n = 205), periodontitis (n = 345), and healthy (n = 343). Fourteen single-nucleotide polymorphisms (SNPs) were investigated: LDLR gene (rs5925 and rs688), APOB (rs676210, rs1042031, and rs693), ABCC8 (rs6544718 and 6544713), LPL (rs28524, rs3735964, and rs1370225), HNF1A (rs2650000), APOE (rs429358 and rs7412), and HNF4A (rs1800961). Multiple linear and logistic regressions (adjusted for covariates) were made for all populations and stratified by sex and smoking habits. RESULTS: Individuals carrying APOB-rs1042031-CT (mainly women and never smokers) had a lower risk of developing periodontitis and T2DM (T2DM+P); altogether, this genotype was related with healthier glycemic, lipid, and periodontal parameters. Significant disease-phenotype associations with gene-sex interaction were also found for carriers of APOB-rs1676210-AG, HNF4A-rs1800961-CT, ABCC8-rs6544718-CT, LPL-rs13702-CC, and LPL-rs285-CT. CONCLUSIONS: Polymorphisms in lipid metabolism genes are associated with susceptibility to T2DM-periodontitis comorbidities, demonstrating gene-sex interaction. The APOB-rs1042031 was the most relevant gene marker related to glucose and lipid metabolism profiles, as well as with obesity and periodontitis.

Short-term clinical and immunologic effects of scaling and root planing with Er:YAG laser in chronic periodontitis.

BACKGROUND: Recently, the erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser has been used for periodontal therapy. This study compared Er:YAG laser irradiation (100 mJ/pulse, 10 Hz, 12.9 J/cm(2)) with or without conventional scaling and root planing (SRP) to SRP only for the treatment of periodontal pockets affected with chronic periodontitis. METHODS: Twenty-one subjects with pockets from 5 to 9 mm in non-adjacent sites were studied. In a split-mouth design, each site was randomly allocated to a treatment group: SRP and laser (SRPL), laser only (L), SRP only (SRP), or no treatment (C). The plaque index (PI), gingival index (GI), bleeding on probing (BOP), and interleukin (IL)-1beta levels in crevicular fluid were evaluated at baseline and at 12 and 30 days postoperatively, whereas probing depth (PD), gingival recession (GR), and clinical attachment level (CAL) were evaluated at baseline and 30 days after treatment. A statistical analysis was conducted (P <0.05). RESULTS: Twelve days postoperatively, the PI decreased for SRPL and SRP groups (P <0.05); the GI increased for L, SRP, and C groups but decreased for the SRPL group (P <0.05); and BOP decreased for SRPL, L, and SRP groups (P <0.01). Thirty days postoperatively, BOP decreased for treated groups and was lower than the C group (P <0.05). PD decreased in treated groups (P <0.001), and differences were found between SRPL and C groups (P <0.05). CAL gain was significant only for the SRP group (P <0.01). GR increased for SRPL and L groups (P <0.05). No difference in IL-1beta was detected among groups and periods. CONCLUSION: Er:YAG laser irradiation may be used as an adjunctive aid for the treatment of periodontal pockets, although a significant CAL gain was observed with SRP alone and not with laser treatment.

Periodontal disease severity in subjects with dementia: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Despite clinical trials and reviews attempt to assess a possible relationship between dementia and periodontal disease, no meta-analysis has been performed and this issue remains undetermined. The aim of this study is to conduct a systematic review and meta-analysis to assess severity of periodontitis in subjects with dementia. METHODS: The search was conducted in Pubmed, Embase/MEDLINE. Two independent reviewers extracted data and assessed the risk bias (Newcastle-Ottawa scale). Meta-analyses were performed using the means of probing depth (PD) and clinical attachment loss (CAL) in patients with or without dementia. The mean difference were analyzed (P ≤ 0.05). RESULTS: Fourteen studies were included in the systematic review. In the qualitative analysis, most studies reported higher prevalence of periodontal disease in dementia patients. The studies had low risk of bias and two meta-analyses were performed for each parameter, including or not a cross-sectional study. The meta-analyses including the cross-sectional study demonstrated significant association between dementia and periodontal disease (mean difference: PD = 1.41; CAL = 1.40, P < 0.05), however, it wasn't confirmed when the cross-sectional study was removed (1.25 mm, P < 0.22) and CAL (1.20 mm, P < 0.22). CONCLUSION: Although the qualitative analysis have suggested worse periodontal conditions in dementia patients, due to different study types and the high heterogeneity among them, the meta-analysis does not support the association between dementia and severity of periodontal disease.

Effect of ER:YAG and diode laser irradiation on the root surface: morphological and thermal analysis.

BACKGROUND: The aim of the present study was to compare the effects of Er:YAG and diode laser treatments of the root surface on intrapulpal temperature after scaling and root planing with hand instruments. METHODS: Fifteen extracted single-rooted teeth were scaled and root planed with hand instruments. The teeth were divided into 3 groups of 5 each and irradiated on their buccal and lingual surfaces: group A: Er:YAG laser, 2.94 microm/100 mJ/10 Hz/30 seconds; group B: diode laser, 810 nm/1.0 W/0.05 ms/30 seconds; group C: diode laser, 810 nm/1.4 W/0.05 ms/30 seconds. The temperature was monitored by means of a type T thermocouple (copper-constantan) positioned in the pulp chamber to assess pulpal temperature during and before irradiation. Afterwards, the specimens were longitudinally sectioned, and the buccal and lingual surfaces of each root were analyzed by scanning electron microscopy. RESULTS: In the Er:YAG laser group, the thermal analysis revealed an average temperature of -2.2 +/- 1.5 degrees C, while in the diode laser groups, temperatures were 1.6 +/- 0.8 degrees C at 1.0 W and 3.3 +/- 1.0 degrees C at 1.4 W. Electronic micrographs revealed that there were no significant morphological changes, such as charring, melting, or fusion, in any group, although the specimens were found to be more irregular in the Er:YAG laser group. CONCLUSIONS: The application of Er:YAG and diode lasers at the utilized parameters did not induce high pulpal temperatures. Root surface irregularities were more pronounced after irradiation with an Er:YAG laser than with a diode laser.

A histologic assessment of the influence of low-intensity laser therapy on wound healing in steroid-treated animals.

OBJECTIVE: The aim of the present study was to evaluate the effect of low-intensity laser therapy on the wound healing process treated with steroid. BACKGROUND DATA: Various biological effects have been associated with low-level laser therapy (LLLT). MATERIALS AND METHODS: Forty-eight rats were used, and after execution of a wound on the dorsal region of each animal, they were divided into 4 groups (n = 12), receiving the following treatments: G1 (control), wounds and animals received no treatment; G2, wounds were treated with LLLT; G3, animals received an intraperitoneal injection of steroid dosage (2 mg/kg of body weight); G4, animals received steroid and wounds were treated with LLLT. The laser emission device used was a GaAIAs (904 nm), in a contact mode, with 2.75 mW gated with 2.900 Hz during 120 sec (33 J/cm(2)). After the period of 3, 7, and 14 days, the animals were sacrificed and the parts sent to histological processing and dyed using hematoxylin and eosin (HE) and Masson trichromium (MT) techniques. RESULTS: The results have shown that the wounds treated with steroid had a delay in healing, while LLLT accelerated the wound healing process. Also, wounds treated with laser in the animals treated with steroid presented a differentiated healing process with a larger collagen deposition and also a decrease in both the inflammatory infiltrated and the delay on the wound healing process. CONCLUSION: LLLT accelerated healing, caused by the steroid, acting as a biostimulative coadjutant agent, balancing the undesirable effects of cortisone on the tissue healing process.

Platelet-rich plasma, low-level laser therapy, or their combination promotes periodontal regeneration in fenestration defects: a preliminary in vivo study.

BACKGROUND: This study histomorphometrically analyzes the influence of platelet-rich plasma (PRP), low-level laser therapy (LLLT), or their combination on the healing of periodontal fenestration defects (PFDs) in rats. METHODS: PFDs were surgically created in the mandibles of 80 rats. The animals were randomly divided into four groups: 1) C (control) and 2) PRP, defects were filled with blood clot or PRP, respectively; 3) LLLT and 4) PRP/LLLT, defects received laser irradiation, were filled with blood clot or PRP, respectively, and then irradiated again. Animals were euthanized at either 10 or 30 days post-surgery. Percentage of new bone (NB), density of newly formed bone (DNB), new cementum (NC), and extension of remaining defect (ERD) were histomorphometrically evaluated. Data were statistically analyzed (analysis of variance; Tukey test, P <0.05). RESULTS: At 10 days, group PRP presented ERD significantly lower than group C. At 30 days, group PRP presented NB and DNB significantly greater than group C. Groups LLLT, PRP, and PRP/LLLT showed significant NC formation at 30 days, with collagen fibers inserted obliquely or perpendicularly to the root surface. NC formation was not observed in any group C specimen. CONCLUSIONS: LLLT, PRP, or their combination all promoted NC formation with a functional periodontal ligament. The combination PRP/LLLT did not show additional positive effects compared to the use of either therapy alone.

Platelet-rich plasma derived from bone marrow aspirate promotes new cementum formation.

BACKGROUND: This study evaluates the influence of platelet-rich plasma derived from bone marrow aspirate (PRP-BMA) on the healing of periodontal fenestration defects in rats. METHODS: Periodontal fenestration defects were surgically created in the mandibles of 40 rats. The animals were randomly divided into two groups, control and PRP-BMA, in which defects were filled with blood clot or PRP-bma, respectively. Animals were euthanized at either 10 or 30 days post-surgery. Histologic, histometric, and immunohistochemical analyses were performed. Percentage of new bone area (NBA), area of bone trabeculae (ABT), new cementum (NC), and extension of remaining defect were histometrically evaluated. Proliferating cell nuclear antigen (PCNA), bone sialoprotein (BSP), osteocalcin (OCN), and tartrate-resistant acid phosphatase (TRAP) immunohistochemical staining were performed. Immunolabeled cells were quantified. Data were statistically analyzed (analysis of variance; Tukey, P <0.05). RESULTS: At 10 days, control and PRP-BMA groups presented similar amounts of NBA and ABT; NC formation was not observed. At 30 days, control and PRP-BMA groups presented similar amounts of NBA and ABT; the PRP-BMA group showed NC formation with collagen fibers inserted obliquely or perpendicularly to the root surface. NC formation was not observed in any control group specimen. PRP- BMA presented higher numbers of PCNA-positive and BSP-positive cells than control at 10 and 30 days post-surgery. No significant differences in the number of either OCN-positive or TRAP-positive cells were observed between groups at 10 or 30 days. CONCLUSION: PRP-BMA promoted NC formation with a functional periodontal ligament when applied at experimental periodontal fenestration defects.

The role of obesity as a modifying factor in patients undergoing non-surgical periodontal therapy.

BACKGROUND: Earlier studies have shown an association between obesity and periodontitis, which is mediated by cytokine production. The aim of this study is to assess the role of obesity as a modifying factor on periodontal clinical parameters and on circulating proinflammatory cytokine levels in subjects undergoing non-surgical periodontal treatment. METHODS: Twenty-seven obese subjects and 25 normal-weight subjects were enrolled in this study. Subjects in both groups had generalized chronic periodontitis. The periodontal parameters measured before and 3 months after non-surgical periodontal therapy were: visible plaque index, bleeding gingival index, bleeding on probing, probing depth, and clinical attachment level. In addition, subjects underwent anthropometric measurements and serum analyses of fasting glucose, glycated hemoglobin, interleukin-1ß, interleukin-6, tumor necrosis factor-α, and interferon-γ. RESULTS: Periodontal therapy significantly decreased visible plaque index, bleeding gingival index, bleeding on probing, probing depth of 4 to 6 mm, probing depth ≥7 mm, clinical attachment level of 4 to 6 mm, and clinical attachment level ≥7 mm in both groups (P ≤0.05). Circulating proinflammatory cytokines significantly decreased in obese and normal-weight subjects after periodontal treatment (P ≤0.05). However, interleukin-6 and tumor necrosis factor-α levels remained higher in obese subjects 3 months after treatment (P ≤0.05). CONCLUSION: Obesity does not seem to play a negative role by interfering in the improvement of the periodontal clinical response or decreasing circulating proinflammatory cytokine levels after periodontal treatment.