AIM:This retrospective cohort study aimed to identify pretreatment prognostic factors for tooth survival in teeth with endodontic-periodontal lesions (EPLs). MATERIALS AND METHODS:Teeth with EPLs treated according to a standardised clinical protocol involving periodontal and endodontic treatments were included. Clinical parameters were measured, and the EPL grade was classified according to the 2017 World Workshop criteria. Based on the radiographic characteristics, lesions were categorised as I-shaped (unilateral intrabony defect without apparent apical radiolucency), J-shaped (unilateral intrabony defect with apical radiolucency) and U-shaped (bilateral intrabony defects with apical radiolucency). Survival-time analysis was performed. RESULTS:Of the 187 teeth included, 117 survived over the mean observation period of 3.1 ± 2.1 years (maximum, 8.4 years). The estimated 1- and 5-year tooth survival rates were 83.8% and 58.9%, respectively. Multivariate analysis identified age, EPL grade, probing depth (PD), periapical index, bone loss and I-J-U subclassification as significant prognostic factors for tooth survival. The I-J-U subclassification was significantly associated with tooth survival, suggesting its potential value in prognostic assessment. CONCLUSION:This retrospective cohort study identified age, EPL grade, PD and radiographic shape of bone loss as predicting factors for tooth survival in teeth with EPLs.

This study aimed to investigate the effect of periodontitis on renal function in patients with type 2 diabetes mellitus (T2D) and to explore the potential underlying pathways. A cohort of 73 patients with poorly controlled T2D who received diabetes care was monitored for six months. The association between the changes in renal function and periodontal parameters at baseline was assessed using regression analysis. Causal mediation analysis was performed to examine the effect of periodontitis on renal function mediated by glycemic control. Of the participants, 57 (78.0%) had stage III or IV periodontitis. Hemoglobin A1c levels improved significantly, from 9.5 ± 1.9% to 7.6 ± 1.4% while estimated glomerular filtration rate (eGFR) declined from 76.8 ± 23.7 to 71.8 ± 21.6 mL/min/1.73 m2 (p < 0.001). eGFR decline was significantly associated with periodontitis stage, periodontal epithelial surface area, and periodontal inflamed surface area. Glycemic control did not significantly mediate this association between periodontitis and eGFR decline, whereas the direct effect of periodontitis remained significant. These findings suggest that periodontitis may contribute to renal function decline in patients with T2D, partly through pathways independent of glycemic control.

Obesity is a risk factor for periodontal disease and is associated with socioeconomic status (SES). However, it remains unclear whether SES modifies the relationship between obesity and periodontal disease. This study investigated the influence of SES on the association between obesity and periodontal disease. We used multilevel Poisson regression, after adjusting for potential confounding factors including population-level SES, to analyze the body mass index (BMI) and periodontal parameters of 962 participants (mean age 58.3 years; SD: 13.8). A significant association was observed between obesity and the proportion of teeth with probing pocket depth (PPD) ≥ 4 mm (ratio of means [RM]: 1.25, 95

AIM:The evidence for tooth splinting during periodontal regenerative therapy is limited. We aimed to investigate the adjunctive benefits of tooth splinting on clinical outcomes. MATERIALS AND METHODS:In total, 194 intrabony defects in 126 participants were prospectively evaluated over three years following periodontal regenerative therapy with an enamel matrix derivative. Clinical attachment level (CAL), probing depth (PD) and radiographic bone defect depth (RBD) were assessed. Propensity score matching (PSM) was employed to assign surgical sites to splinting and non-splinting groups, and multilevel regression was used to analyse the impact of tooth splinting on clinical outcomes. RESULTS:Using PSM, 37 sites each from 32 and 30 participants in the splinting and non-splinting groups, respectively, were matched using the propensity score. Both groups included 26 and 11 sites with tooth mobility degrees 0 and 1, respectively. Significant improvements in CAL, PD and RBD were observed in both groups compared to baseline over the 3-year period. However, there were no significant differences among these parameters between the groups at the 1- and 3-year follow-ups. CONCLUSION:No statistically significant adjunctive benefits of tooth splinting were observed in this study. However, further research with a larger sample size may be required to detect smaller but potentially clinically relevant effects.

ObjectiveThis study aims to investigate the mechanisms underlying the impaired healing response by diabetes after periodontal therapy.BackgroundOutcomes of periodontal therapy in patients with diabetes are impaired compared with those in patients without diabetes. However, the mechanisms underlying impaired healing response to periodontal therapy have not been sufficiently investigated.Materials and MethodsZucker diabetic fatty (ZDF) and lean (ZL) rats underwent experimental periodontitis by ligating the mandibular molars for one week. The gingiva at the ligated sites was harvested one day after ligature removal, and gene expression was comprehensively analyzed using RNA-Seq. In patients with and without type 2 diabetes (T2D), the corresponding gene expression was quantified in the gingiva of the shallow sulcus and residual periodontal pocket after non-surgical periodontal therapy.ResultsLigation-induced bone resorption and its recovery after ligature removal were significantly impaired in the ZDF group than in the ZL group. The RNA-Seq analysis revealed 252 differentially expressed genes. Pathway analysis demonstrated the enrichment of downregulated genes involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. PPAR alpha and PPAR gamma were decreased in mRNA level and immunohistochemistry in the ZDF group than in the ZL group. In clinical, probing depth reduction was significantly less in the T2D group than control. Significantly downregulated expression of PPAR alpha and PPAR gamma were detected in the residual periodontal pocket of the T2D group compared with those of the control group, but not in the shallow sulcus between the groups.ConclusionsDownregulated PPAR subtypes expression may involve the impaired healing of periodontal tissues by diabetes.

AIM:This study aimed to investigate the effects of diabetes care on periodontal inflammation. MATERIALS AND METHODS:This prospective cohort study included 51 Japanese patients with type 2 diabetes who underwent intensive diabetes care including educational hospitalization and regular outpatient treatment for 6 months. Dental prophylaxis without subgingival scaling was provided three times during the observational period. Associations between changes in periodontal parameters and glycaemic control levels were evaluated using multiple regression analysis. RESULTS:Overall, 33 participants (mean age: 58.7 ± 12.9) were followed up for 6 months. At baseline examination, 82% were diagnosed with Stage III or IV periodontitis. Haemoglobin A1c (HbA1c) level changed from 9.6 ± 1.8% at baseline to 7.4 ± 1.3% at 6 months. The ratio of probing pocket depth (PPD) ≥4 mm, bleeding on probing (BOP), full-mouth plaque control record (PCR), periodontal epithelial surface area (PESA) and periodontal inflamed surface area (PISA) also significantly improved. The reduction in PPD and PESA was significantly associated with changes in both HbA1c and fasting plasma glucose (FPG) levels, and the reduction in PISA was significantly associated with an improvement in FPG after adjusting for smoking, change in body mass index and full-mouth PCR. CONCLUSIONS:This is the first study to report a significant improvement in PPD and BOP after intensive diabetes care and dental prophylaxis without subgingival scaling. CLINICAL TRIAL REGISTRATION NUMBER:UMIN000040218.

BACKGROUND There have been limited studies with statistically sufficient sample sizes for assessment of suitable bone defect morphology for combination therapy with enamel matrix derivative (EMD) and bone grafting. The aim of this study was to investigate the appropriate feature of intrabony defects, such as bone defect angle (DA) and the containment by bony wall, for yielding the additional benefit of bone grafting in combination with periodontal regenerative therapy using EMD. METHODS Following periodontal regenerative therapy using EMD with or without autologous bone grafting, 282 intrabony defects of 177 participants were maintained for 3 years. Multilevel linear regression analysis was performed to evaluate the radiographic bony defect depth (RBD) reduction after adjusting for confounders. RESULTS The baseline parameters, except for the proportion of contained bony defects and tooth mobility, did not differ significantly between the groups with and without bone grafts. There was no significant difference in the improvement of clinical parameters between the groups. The 1- and 3-year reduction of RBD showed significant inverse correlations with preoperative DA only in the group without bone graft. Furthermore, multivariate analysis showed a significant interaction between DA at baseline ≥40° and adjunctive bone grafting in the reduction of RBD, regardless of the number of bony walls. CONCLUSION Adjunctive autologous bone grafting with enamel matrix derivative might be significantly beneficial for defect depth improvement in the case of DA at baseline ≥40°.

BACKGROUND This study aimed to investigate the effects of low-level erbium-doped: yttrium, aluminum, and garnet (Er:YAG) laser irradiation on periodontal tissue healing and regeneration through angiogenesis in vivo and in vitro studies. METHODS Intrabony defects were surgically created in the bilateral maxilla molar of rats. The defects were treated by open flap debridement (OFD) with Er:YAG laser, including low-level laser irradiation (LLLI) to bone and blood clot surfaces, or conventional procedures. The mRNA expression of vascular endothelial growth factor (VEGF) in the surgical sites was quantified using real-time polymerase chain reaction. The decalcified specimens were prepared for histometric analysis. Also, LLLI was performed on human umbilical vein endothelial cells to evaluate the effects on angiogenesis. Cell proliferation, VEGF expression, and tube formation were assessed. In addition, capsazepine (CPZ), a selective inhibitor of transient receptor potential vanilloid 1 (TRPV1), treatment was performed before LLLI for the same assays. RESULTS OFD using Er:YAG laser did not generate thermal damage on bone or root surfaces. LLLI accelerated hemostasis by coagulation of the superficial layers of blood clots in the laser-treated group. Postoperative healing was sound in all animals in both groups. VEGF expression and bone formation were significantly increased in the laser-treated group compared to those in the conventional treatment group. In vitro, cell proliferation and VEGF expression were significantly increased in the LLLI group compared to the control group. Tube-formation assays showed that LLLI significantly promoted angiogenesis. CPZ treatment significantly suppressed VEGF expression and tube formation following LLLI. CONCLUSIONS This study suggests that Er:YAG laser irradiation may promote periodontal tissue healing by enhancing angiogenetic effect of endothelial cells via TRPV1.

Diabetes mellitus (DM) is associated with periodontal disease. Clinically, periodontal treatment is less effective for patients with DM. Oxidative stress is one of the mechanisms that link DM to periodontitis. The production of reactive oxygen species (ROS) is increased in the periodontal tissues of patients with DM and is involved in the development of insulin resistance in periodontal tissues. Insulin resistance decreases Akt activation and inhibits cell proliferation and angiogenesis. This results in the deterioration of wound healing and tissue repair in periodontal tissues. Antioxidants and insulin resistance ameliorants may inhibit ROS production and improve wound healing, which is worsened by DM. This manuscript provides a comprehensive review of the most recent basic and clinical evidence regarding the generation of ROS in periodontal tissues resulting from microbial challenge and DM. This study also delves into the impact of oxidative stress on wound healing in the context of periodontal and dental implant therapies. Furthermore, it discusses the potential benefits of administering antioxidants and anti-insulin resistance medications, which have been shown to counteract ROS production and inflammation. This approach may potentially enhance wound healing, especially in cases exacerbated by hyperglycemic conditions.

Abstract Background This study aims to investigate the mechanisms underlying the exacerbated healing response by diabetes after periodontal therapy. Methods Zucker diabetic fatty (ZDF) and lean (ZL) rats underwent experimental periodontitis by ligating the mandibular molars for one week. The gingiva at the ligated sites was harvested one day after ligature removal, and gene expression was comprehensively analyzed using RNA-Seq. In patients with and without type-2 diabetes (T2D), the corresponding gene expression was quantified in the gingiva of the shallow sulcus and residual periodontal pocket after non-surgical periodontal therapy. Results Ligation-induced bone resorption and its recovery after ligature removal were significantly impaired in the ZDF group than in the ZL group. The RNA-Seq analysis revealed 252 differentially expressed genes. Pathway analysis demonstrated an enrichment of downregulated genes involved in peroxisome proliferator-activated receptor (PPAR) signaling pathway. PPARα and PPARγ were decreased in mRNA level and immunohistochemistry in the ZDF group than in the ZL group. In clinical, less probing depth reduction and significantly downregulated expression of PPARα and PPARγ were detected in the residual periodontal pocket of the T2D group compared with those of the control group. Conclusions Downregulated PPAR subtypes expression may involve the impaired healing of periodontal tissues by diabetes.

Malnutrition-inflammation-atherosclerosis (MIA) syndrome is a significant risk factor for mortality in patients undergoing hemodialysis. This study aimed to investigate the association between MIA syndrome and oral health status in hemodialysis patients. A cross-sectional study was conducted on 254 hemodialysis patients. Comprehensive medical and dental examinations were performed. Three components were included to define MIA syndrome: Geriatric Nutritional Risk Index, serum high-sensitivity C-reactive protein, and history of cardiovascular events as indicators of malnutrition, inflammation, and atherosclerosis, respectively. The association of MIA syndrome components with periodontitis and occlusal support was examined by multiple-ordered logistic regression analysis. Of 254 participants, 188 (74.0%) had at least one component of MIA syndrome. After adjusting for possible confounding factors, severe periodontitis was significantly associated with presence of more components of MIA syndrome (odds ratio [OR]: 2.64, 95% confidence interval [CI], 1.44-4.84, p=0.002) and inflammation and malnutrition components (OR: 2.47 and 3.46, 95% CI 1.16-5.28 and 1.70-7.05, p=0.020 and 0.001). On the other hand, occlusal support, evaluated by Eichner index, was not significantly associated with MIA syndrome or any of its components. In conclusion, periodontitis is associated with MIA syndrome, particularly with inflammation and malnutrition in hemodialysis patients, independent of occlusal support.

Socio-economic status (SES) and smoking are risk factors for periodontitis; however, their interaction has not been determined. We investigated the effect of modification of SES and smoking with periodontal conditions. Data on the social background, smoking status, and dental examination of 1033 individuals residing in the Tokyo Metropolitan District were analyzed. The outcomes were the number of remaining teeth and the proportion of teeth with probing pocket depth (PPD) ≥ 4 mm and ≥ 6 mm. Multilevel linear and Poisson regression analyses were performed after adjusting for possible confounding factors, including SES, assessed by the average income of the residential area. The mean number of remaining teeth was 24.6 ± 4.8, and the proportion of teeth with PPD ≥ 4 mm and ≥ 6 mm was 31.2 ± 28.5

Background/purpose: Diabetes mellitus (DM) induces microangiopathy in various tissues, leading to several complications. However, limited studies have reported the impact of diabetes on gingival capillaries. The aim of this study was to investigate the morphological evaluation and to analyze the influence of diabetes on gingival capillaries.Materials and methods: Medical interviews and periodontal examinations were performed on 29 patients with periodontitis. The subjects were divided into two groups: those with or without type 2 diabetes (DM or non-DM group). Gingival capillary density and morphology in the buccal marginal gingiva were evaluated using a capillary blood flow scope (magnification: x 560).Results: Probing pocket depth, plaque index, and gingival index were not significantly different between the DM and non-DM groups. The mean HbA1c was 7.9 & PLUSMN; 1.5% in the DM group (n Z 14). Using an oral moisturizing gel as immersion agent, gingival capillaries can be observed under high magnification. The gingival capillary density was 10.5 & PLUSMN; 3.9/mm2 and 9.1 & PLUSMN; 2.7/mm2 in the non-DM group and DM group, respectively. There were no significant differences between the groups. Gingival capillary density was not significantly associated with probing pocket depth, plaque index, or gingival index. The proportion of capillary morpholog-ical abnormalities was significantly higher in the DM group than non-DM group. However, capil-lary morphological abnormalities were not significantly associated with the HbA1c.Conclusion: The present study first documented the morphological abnormalities of gingival capillaries in patients with type 2 diabetes using the capillary blood flow scope. Gingival capil-lary density might not be affected by diabetes.(C) 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

OBJECTIVE:Few studies have reported on the impact of oxidative stress on the dental implant failure. The aim of this study was to investigate the impact of hyperglycemia-induced oxidative stress on dental implant osseointegration in diabetes mellitus (DM).METHODS:Acid-treated titanium implants were bilaterally placed in the maxillary alveolar ridge of streptozotocin-induced diabetic (DM group) and control rats after extraction of first molars. Histological analysis and micro-push-out test were performed 4 weeks after surgery. Oxidative stress and osteogenic markers in the surrounding bone were quantified by real-time polymerase chain reaction. In the in vitro study, rat bone marrow-derived mesenchymal stem cells (BMMSCs) were cultured on acid-treated titanium discs in a high-glucose (HG) or normal environment. Intracellular reactive oxygen species (ROS), cell proliferation, alkaline phosphatase (ALP) activity, and extracellular calcification were evaluated following antioxidant treatment with N-acetyl-L-cysteine (NAC).RESULTS:The implant survival rate was 92.9% and 75.0% in control and DM group, respectively. Bone-implant contact and push-out loads were significantly lower in the DM group. Expression of superoxide dismutase 1 at the mRNA level and on immunohistochemistry was significantly lower in the DM group. In vitro experiments revealed that the HG condition significantly increased ROS expression and suppressed the proliferation and extracellular calcification of BMMSCs, while NAC treatment significantly restored ROS expression, cell proliferation, and calcification. The ALP activity of both groups was not significantly different.CONCLUSION:In diabetes, high-glucose-induced oxidative stress downregulates proliferation and calcification of BMMSCs, impairing osseointegration and leading to implant failure.

Background Limited evidence are available regarding the influence of diabetes on periodontitis in hemodialysis patients, although the association between diabetes and periodontal disease is well-known. Objective This study aimed to investigate the influence of type 2 diabetes mellitus (T2D) and its control level on periodontal disease and the number of missing teeth in patients undergoing hemodialysis. Subjects and methods A single-center cross-sectional study was conducted on 246 Japanese patients with end-stage renal disease undergoing hemodialysis. Comprehensive medical and dental examinations were performed. The association between severity of periodontitis and T2D was examined by multiple ordered logistic regression analysis. A multiple linear regression model was fitted to assess the association of periodontal probing depth (PPD) ≥4 mm and the number of missing teeth with T2D (n = 125). A subgroup analysis involving only the patients with T2D was performed to investigate the factors associated with missing teeth among them. Results After adjusting for confounders, the classification of periodontitis severity was significantly advanced in patients with T2D (odds ratio: 1.64, 95% confidence interval [CI]: 1.02–2.65, p = 0.04). The proportion of PPD≥4 mm sites and the number of missing teeth was significantly associated with T2D (coefficient: 4.1 and 5.7, 95% CI: 0.2–8.0 and 3.4–8.0, p = 0.04 and <0.001, respectively). Subgroup analysis of T2D patients revealed that glycoalbumin levels (coefficient: 0.4, 95% CI: 0.03–0.80, p = 0.03), but not hemoglobin A1c levels (coefficient: 0.8, 95% CI: -1.0–2.7, p = 0.37), were significantly associated with the number of missing teeth. Conclusion T2D was significantly associated with periodontitis and the number of missing teeth in hemodialysis patients. Moreover, it is first documented that poor glycemic control, as determined by glycoalbumin levels, was significantly associated with the number of missing teeth in hemodialysis patients with T2D.

Introduction: Fibroblast growth factor-2 (FGF-2) has been reported to promote periodontal tissue regeneration. However, no study has investigated the long-term prognosis of periodontal regenerative therapy using FGF-2 to date. The aim of this study was to observe the long-term outcomes as well as to investigate the factors affecting the prognosis of periodontal regenerative therapy using FGF-2. Methods: Sixty intrabony defects were prospectively investigated for three years after periodontal regenerative therapy with recombinant human FGF-2 (rhFGF-2) by evaluating probing pocket depth (PPD) and radiographic bone defect depth (RBD). The factors influencing RBD were assessed by con-ducting a multivariate linear regression analysis after adjusting for confounders. Results: The mean age of the participants was 62.4 +/- 13.4 years, and baseline PPD and RBD were 6.1 +/- 1.9 mm and 4.5 +/- 1.8 mm, respectively. At six months, one year, and three years after surgery, PPD and RBD had significantly improved to 4.2 +/- 1.7, 3.7 +/- 1.4, 4.0 +/- 1.9 mm and to 3.08 +/- 2.05, 2.73 +/- 1.90, 2.51 +/- 2.15 mm, respectively. At the three-year examination, a significant positive association was deteced between RBD reduction and RBD at baseline, while the association was not significant between RBD reduction and the radiographic bony angle, number of bony walls of the defect, or the furcation involvement at baseline. Conclusions: rhFGF-2 was effective for alveolar bone regeneration in patients with periodontitis and maintained the improved parameters over the three-year observation period. The radiographic bone defect depth at baseline was found to be the factor affecting the periodontal regenerative therapy using rhFGF-2 in the intrabony defects. Trial registration number: UMIN000027979. (c) 2022, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

Background Information regarding periodontal regenerative therapy in patients with diabetes mellitus (DM) is limited. This pilot study compared the regenerative outcomes of minimally invasive periodontal surgery using enamel matrix derivative (EMD) between DM and non-DM patients. Methods This prospective study included deep intrabony defects in patients with or without type 2 DM. Minimally invasive surgical technique (MIST) or modified MIST (M-MIST) using EMD, without bone graft materials, was performed. Periodontal examination and intraoral radiography were performed at baseline, 6 months, and 1 and 3 years after surgery. Results Ten sites of 10 subjects in the DM group, and 20 sites of 18 subjects in non-DM group were evaluated (mean age; 67.5 +/- 7.6 and 63.1 +/- 9.7, respectively). Probing depth significantly decreased from 7.1 +/- 1.6 and 7.0 +/- 1.3 mm to 2.2 +/- 0.9 and 2.3 +/- 1.1 mm at the 1-year examination in the DM and non-DM groups, respectively. Clinical attachment level (CAL) gain and radiographical defect fill at the 3-year examination were 3.8 +/- 1.1 mm and 58.3% +/- 10.4%, respectively, in the DM group, and 4.1 +/- 1.1 mm and 65.5% +/- 18.8%, respectively, in the non-DM group, showing no significant differences between the groups. Multiple regression analysis showed no significant association of CAL gain with DM or age after adjustments for relevant confounders. Conclusions This is the first documented study of successful periodontal tissue regeneration in patients with DM. Minimally invasive surgery combined with EMD yielded significant clinical attachment gain and bone fill in the DM and non-DM groups at comparable levels.

INTRODUCTION:The aim was to investigate the relationship of full-mouth inflammatory parameters of periodontal disease with diabetes and obesity. RESEARCH DESIGN AND METHODS:This cross-sectional study conducted diabetes-related examinations and calculated periodontal inflamed and epithelial surface area (PISA and PESA) of 71 Japanese patients with type 2 diabetes. Multiple linear regression analyses were performed to evaluate associations between PISA or PESA and diabetes and obesity parameters. RESULTS:Median value of body mass index (BMI), hemoglobin A1c (HbA1c) level, fasting plasma glucose (FPG) level, and visceral fat area (VFA) were 25.7 kg/m2, 9.1%, 151 mg/L, and 93.3 cm2, respectively. PISA and PESA were significantly associated with HbA1c after adjusting for age, sex, BMI, smoking status, and full-mouth plaque control level (PISA: coefficient=38.1, 95% CI 8.85 to 67.29, p=0.001; PESA: coefficient=66.89, 95% CI 21.44 to 112.34, p=0.005). PISA was also significantly associated with the highest FPG tertile (>175 mg/dL) after adjusting for confounders (coefficient=167.0, 95% CI 48.60 to 285.4, p=0.006). PISA and PESA were not significantly associated with BMI or VFA. CONCLUSION:PISA was associated with FPG and HbA1c, but not with obesity parameters, independent from confounders such as full-mouth plaque control level in patients with type 2 diabetes.

AIMS:The impact of periodontal inflammation on lipid metabolism is controversial. This study aimed to investigate the association between full-mouth periodontal inflammation and serum lipid levels.MATERIALS AND METHODS:In this cross-sectional study, we performed periodontal and bacteriological examinations during medical checkup on 131 subjects. The association between the periodontal inflamed surface area (PISA) and the lipid markers was analyzed by multiple linear regression, adjusting for age, sex, smoking, and body mass index.RESULTS:Overall, 118 medically healthy participants were analyzed. The proportions of none, mild, moderate, and severe periodontitis were 37.3%, 32.2%, 25.4%, and 5.1%, respectively. Multivariate analysis showed that high-density lipoprotein cholesterol was significantly higher in participants with the lowest tertile of PISA values (PISA low, coefficient: 7.94; 95% confidence interval [CI]: 1.63, 14.26, p = .01) compared to those in other tertiles (PISA high). Low-density/high-density lipoprotein cholesterol and total/high-density lipoprotein cholesterol ratios were significantly lower in the PISA-low group than the PISA-high group (coefficient: -0.26 and -0.30; 95% CI: -0.50, -0.02, and -0.59, -0.0002; p = .04 and .0498). Serum high-sensitivity C-reactive protein level, but not serum Porphyromonas gingivalis antibody titer, partly explained the association between PISA and high-density lipoprotein cholesterol. A significant interaction between female sex and PISA values toward high-density lipoprotein cholesterol level was detected.CONCLUSION:Periodontal inflammation was inversely associated with higher high-density lipoprotein cholesterol, especially in females. Elevated serum C-reactive protein partly explained this association.

This review investigated whether the adjunctive use of antioxidants with periodontal therapy improves periodontal parameters in patients with type 2 diabetes. A systematic and extensive literature search for randomized controlled trials (RCTs) conducted before April 2021 was performed on the PubMed, Cochrane Library, and Web of Science databases. The risk of bias was assessed using the Cochrane risk-of-bias tool. A meta-analysis was performed to quantitatively evaluate the clinical outcomes following periodontal therapy. After independent screening of 137 initial records, nine records from eight RCTs were included. The risk-of-bias assessment revealed that all RCTs had methodological weaknesses regarding selective bias, although other risk factors for bias were not evident. This meta-analysis of two RCTs showed that periodontal pocket depths were significantly reduced in the groups treated with combined non-surgical periodontal therapy and melatonin than in those treated with non-surgical periodontal therapy alone. The present systematic review and meta-analysis suggest that the adjunctive use of melatonin, resveratrol, omega-3 fatty acids with cranberry juice, propolis, and aloe vera gel with periodontal therapy significantly improves periodontal disease parameters in patients with type 2 diabetes, and melatonin application combined with non-surgical periodontal therapy might significantly reduce periodontal pocket depth. However, there are still limited studies of melatonin in combination with non-surgical periodontal therapy in Type 2 diabetic patients, and more well-designed RCTs are required to be further investigated.