Epidemiologic relationship between periodontitis and type 2 diabetes mellitus

Epidemiologic relationship between periodontitis and type 2 diabetes mellitus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Epidemiologic relationship between periodontitis and type 2 diabetes mellitus Chenzhou Wu, Yihang Yuan, Hang-hang Liu, Shensui Li, Bowen zhang, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.9843/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Jul, 2020 Read the published version in BMC Oral Health → Version 2 posted 9 You are reading this latest preprint version Show more versions Abstract Objectives: To systematically review the epidemiologic relationship between periodontitis and type 2 diabetes mellitus (T2DM). Materials and Methods: Four electronic databases were searched up until December 2018. The manual search included the reference lists of the included studies and relevant journals. Observational studies evaluating the relationship between T2DM and periodontitis were included . Meta-analyses were conducted using STATA. Results: A total of 53 observational studies were included. The Adjusted T2DM prevalence was significantly higher in periodontitis patients (OR=4.04, p=0.000), and vice versa (OR=1.58, p=0.000). T2DM patients had significantly worse periodontal status, as reflected in a 0.61 mm deeper periodontal pocket, a 0.89 mm higher attachment loss and approximately 2 more lost teeth (all p=0.000), than those without T2DM. The results of the cohort studies found that T2DM could elevate the risk of developing periodontitis by 34% (p=0.002). The glycemic control of T2DM patients might result in different periodontitis outcomes. Severe periodontitis increased the incidence of T2DM by 53% (p=0.000), and this result was stable. In contrast, the impact of mild periodontitis on T2DM incidence (RR=1.28, p=0.007) was less robust. Conclusions: There is an evident bidirectional relationship between T2DM and periodontitis. Further well-designed cohort studies are needed to confirm this finding. Clinical Relevance: Both dentists and physicians need to be aware of the strong connection between periodontitis and T2DM. Controlling these two diseases might help prevent each other’s incidence. Dentistry Epidemiology Diabetes mellitus type 2 Periodontitis Systematic review Meta-analysis Epidemiologic Studies Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Diabetes mellitus (DM) is a common metabolic disease resulting from a defect in insulin secretion, a defect in insulin action or a combination of both [1]. Type 2 DM (T2DM) results from the body’s ineffective use of insulin and comprises 90% of people with DM worldwide [2]. The number of people with DM has risen rapidly in the last several decades from 108 million in 1980 to 422 million in 2014, and the number is likely to be more than double in the next 20 years. Furthermore, the WHO projected that diabetes will be the seventh leading cause of death in 2030 [3]. Periodontitis is a chronic, multifactorial inflammatory disease in the underlying supporting tissues surrounding the teeth. Sufferers may experience gingivitis, loss of periodontal attachment, resorption of alveolar bone, and eventually tooth loss [4]. Severe periodontitis, which is the sixth most prevalent chronic disease among the general population, affects nearly 750 million people worldwide and is thought to affect people’s chewing ability, nutritional status and quality of life [5,6]. T2DM and periodontitis have a bidirectional relationship that is well documented in many reviews and epidemiological studies [7-9]. Periodontitis is defined as the sixth complication of DM, which means that DM can promote the progression of periodontitis [10]. Conversely, periodontitis is now known as a risk factor for worsening glycemic control and may increase the risk for diabetic complications [11]. Mechanistically, T2DM influences periodontitis initiation and progression by causing a hyperinflammatory response, impairing bone repair processes, and producing advanced glycation end products [9,12,13]. Periodontitis as a local focus of infection can cause the levels of IL-6, TNF-a, and CRP to increase in systems, resulting in increased systemic inflammation, which contributes to insulin resistance [14]. Based on the biological hypothesis, there are substantial randomized controlled trials (RCTs) that show periodontal treatment can improve glycemic control [15]. However, two well-designed large-scale RCTs obtained contradictory results on whether periodontal treatment had an effect on glycated hemoglobin (HbA1c) in T2DM patients [16,17]. The above contradiction raised our curiosity. Do these two common diseases truly affect each other? However, after systematically searching the literature, we found that there was no systemic review to date that answers this question comprehensively. In the present work, we summarized evidence from observational studies to explore this bidirectional relationship. Materials And Methods The protocol of the present systematic review was registered in PROSPERO (CRD42018089993). All procedures were performed following this protocol and in accordance with the MOOSE statements [18]. Two authors independently achieved study selection, quality assessment and data extraction. Any controversies were solved by consensus discussion. Search strategy The search strategy was a combination of an electronic search and a manual search. The manual search included the reference lists of the included studies and the following journals: Diabetes Care, Journal of Periodontology, Journal of Clinical Periodontology and Journal of Dental Research. The following electronic databases were searched without language limitations: MEDLINE (OVID, 1948 to December 2018), EMBASE (OVID, 1984 to December 2018), Chinese BioMedical Literature Database (CBM, 1978 to December 2018), and China National Knowledge Infrastructure (CNKI, 1994 to December 2018). MeSH terms with free text words were combined when conducting electronic searches. The MeSH terms used for PD were “periodontal diseases” and “periodontitis”. The free text word was “(periodont$ or gingivitis or gingiva$ or gum$).mp.”. The MeSH term used for T2DM searching was “diabetes mellitus, type 2”. Free text words were “(((non-insulin or noninsulin or type 2 or type II or matur$ or adult) adj4 (DM or diabet$)) or T2DM or DMT2 or NIDDM or MODY).mp.”. The titles and abstracts were initially scanned, and the full texts of the possibly eligible studies were obtained for final judgment. Inclusion criteria Observational studies (cross-sectional studies, case-control studies and cohort studies) investigating the relationship between T2DM and PD were included. The criteria for the outcomes for periodontitis were clinical attachment loss (CAL), periodontal pocket depth (PPD), number of teeth (NOT), loss of teeth (LOT), alveolar bone loss and community periodontal index (CPI) score. The criteria for the outcomes for T2DM were oral glucose tolerance test (OGTT), HbA1c and fasting plasma glucose (FBG) results. Disease (periodontitis or T2DM) prevalence and incidence were also included. The participants chosen represent the natural population grouping into periodontitis versus non-periodontitis or T2DM versus non-DM. Comparisons based on periodontitis parameters, such as the T2DM incidence/prevalence between patients with low CAL levels and high CAL levels, were also included. Studies investigating outcomes in selected populations, such as comorbid patients, all periodontitis patients, all T2DM patients or all healthy participants (periodontitis-free and T2DM-free), were excluded. Studies were selected according to the aforementioned periodontitis/T2DM-related parameters, medical records or self-reported medical history. Methodological quality assessment The study quality of cohort studies and case-control studies were measured by the Newcastle-Ottawa Scale (NOS) scoring system. Studies with scores less than 3 were regarded as low quality and were excluded. For cross-sectional studies, the Agency for Healthcare Research and Quality (AHRQ) scoring system was applied. Studies with scores less than 3 in the AHRQ scoring system were regarded as low quality and were not included. Data extraction The extracted data were as follows: 1) investigator, 2) country, 3) number of participants, 4) age and sex of the participants, 5) recruitment of participants, 6) selected outcomes, and 7) NOS/AHRQ score. For cohort studies, the follow-up period and number of incident cases were also extracted. Data analysis The software STATA 14.0 was utilized for meta-analysis. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated for continuous data. Odds ratios (ORs) and risk ratios (RRs) with 95% CIs were calculated for dichotomous data. Generic inverse variance (lnOR or lnRR) was used for meta-analyses that included studies that only reported ORs or RRs. Significance was determined by two-sided α values with a cut-off p value of 0.05. All meta-analyses were performed under the random-effects model. Cochran’s Q test and I 2 statistic were used to detect statistical heterogeneity among studies. When P>0.10 and I 2 <50%, the study was regarded as having low heterogeneity; otherwise, it was regarded as having high heterogeneity. Meta-regression was utilized for a meta-analysis that included more than 4 studies to investigate possible sources of heterogeneity. The influence test was conducted by deleting every single study in turn to test whether the results were stable. For a meta-analysis that included more than 10 studies, publication bias was detected by Egger’s test and Begg’s test. The publication was excluded when both test results exhibited p>0.05. If publication bias existed or unstable results were found, the trim and fill method was applied. Results Results of the search and characteristics of the included studies A total of 1387 studies were identified from the primary search after removing duplicate studies. After screening the titles and abstracts, 73 studies were identified for further evaluation. After browsing the full text, 50 studies were considered eligible for inclusion. Twenty-three studies were excluded for various reasons. Among these, 16 studies were excluded because of the study type (7 meta-analyses, 6 review articles and 3 case series reporting periodontal treatment for T2DM patients); 4 studies were excluded because the reported outcomes were insufficient; 2 studies were excluded because they included type 1 DM. Additional reference checking revealed 3 studies that were then included. Journal searching did not add any new studies. Finally, a total of 53 studies were included in the present work. Figure 1 shows the search and inclusion process. Appendix Tables S1 and S2 summarize the characteristics of 43 [19-61] cross-sectional studies and 12 [62,23,63-68,39,69-71] cohort studies, respectively. Appendix Tables S3 and S4 summarize the AHRQ and NOS scores of cross-sectional studies and cohort studies. All included cross-sectional studies and cohort studies had scored higher than 3. After systematically reviewing the included studies, we found that they answered 3 questions (questions 1-3, Q1-3). Specifically, cross-sectional studies gave the answer “Q1: Are periodontitis and T2DM associated with each other?” Cohort studies gave the answer to the other two questions: “Q2: Does T2DM increase the risk of developing periodontitis?”, and “Q3: Does periodontitis increase the risk of developing T2DM?” Results of meta-analyses Q1: Are periodontitis and T2DM associated with each other? A total of 43 cross-sectional studies were included to answer Q1. Evidence was from some national large-scale population-based studies, such as the SHIP, NHANES and KCIS, and some small-sample studies recruiting participants from communities or hospitals. Among these studies, only 14 studies reported adjusted outcomes (Table 1). Six meta-analyses were conducted as follows. Strength of association between periodontitis and T2DM A total of 15 cross-sectional studies with 17924 participants reported the unadjusted OR between these two diseases (Table S1). Since the original data were not directionally adjusted, a meta-analysis was not undertaken. Among the 15 studies, except for 4 studies [21,34,43,51] that reported that the presence of periodontitis was not different between T2DM patients and non-T2DM controls, all the other studies acknowledged that there was a strong connection. Directional adjusted T2DM prevalence (periodontitis versus nonperiodontitis ) A total of 6 cross-sectional studies were included, and all had T2DM prevalence as an outcome. Three studies with 1956 participants were included in a meta-analysis that included a periodontitis diagnosis as an outcome. The included studies had no significant heterogeneity. The results showed that periodontitis patients had significantly higher odds of T2DM prevalence than participants with no periodontitis (OR=4.04, 95% CI 2.48-6.59, p=0.000, Figure 2a). Influence analysis showed that the pooled result was stable (Figure S1a). Other exposure factors included CAL, PPD, LOT, tooth mobility and alveolar bone loss. The results all proved that T2DM was more prevalent in participants with worse periodontal health (Table 1). Directional adjusted periodontitis prevalence (T2DM versus non-DM) A total of 8 cross-sectional studies were included, and all took T2DM as exposure. Three studies with 11459 participants were included in a meta-analysis evaluating periodontitis prevalence. No significant heterogeneity was detected. The results showed that T2DM patients had a significantly higher ORs for PD prevalence (OR=1.58, 95% CI 1.38-1.81, p=0.000, Figure 2b). Influence analysis indicated that the pooled result was stable (Figure S1b). In addition to periodontitis prevalence, other outcomes were divergent. In brief, all studies demonstrated that periodontitis-related parameters were more prevalent in T2DM patients, although some of the differences were not statistically significant. The results are summarized in Table 1. CAL level differences between T2DM and DM-free participants Eighteen cross-sectional studies with 9571 participants were included. Significant heterogeneity was detected (p=0.000; I²=92.5%). Pooled results showed that T2DM patients had a 0.89 mm higher CAL than controls (WMD=0.89, 95% CI 0.64-1.15, p=0.000, Figure 2c). Influence analysis demonstrated that the pooled result was stable (Figure S1c). Publication bias was detected by Egger’s and Begg’s tests (Egger, p=0.003; Begg, p=0.015). Then, we employed the trim and fill method to further evaluate publication bias and found that the results were still significantly positive after adding the hypothesized studies (Table S5). PPD differences between T2DM and DM - free participants Seventeen cross-sectional studies with 8982 participants were included. Significant heterogeneity was detected (P=0.000; I²=94.5%). Pooled results showed that the periodontal pockets of T2DM patients were 0.61 mm deeper than those of controls (WMD=0.61, 95% CI 0.42-0.79, p=0.000, Figure 2d). Influence analysis demonstrated that the pooled result was stable (Figure S1d). Publication bias was detected by Egger’s and Begg’s test (Egger, p=0.015; Begg, p=0.006). However, adding hypothesized studies by the trim and fill method still resulted in strong significance (Table S5). NOT differences between T2DM and DM - free participants Nine cross-sectional studies with 4415 participants were included. Significant heterogeneity was detected (p=0.000; I²=86.6%). Pooled results showed that T2DM patients had, on average, 2.01 fewer teeth remaining than controls. (WMD=-2.01, 95% CI -3.20--0.82, p=0.000, Figure 2e). Influence analysis demonstrated that the pooled result was stable (Figure S1e). No publication bias was detected (Egger, p=0.723; Begg, p=0.917). LOT differences between T2DM and DM - free participants Eleven cross-sectional studies with 3405 participants were included. Significant heterogeneity was detected (P=0.000; I²=90.7%). Pooled results showed that T2DM patients had, on average, lost 2.22 more teeth than controls. (MD=2.22, 95% CI 0.94-3.49, p=0.000, Figure 2f). Influence analysis demonstrated that the pooled result was stable (Figure S1f). No publication bias was detected (Egger, p=0.230; Begg, p=0.755). Meta-regression for meta-analyses with huge heterogeneity Huge statistical heterogeneity existed in the above 4 meta-analyses, and the I 2 ranged from 86.3% to 94.5%; thus, we performed meta-regression to find the possible sources of heterogeneity. The available covariates included the number of participants, mean age, sex composition of the participants, geographic area and AHRQ scores. However, single variable regression did not find any significant covariates; multiple regression of these covariates only explained approximately 10% of the heterogeneity of all meta-analyses (data not shown). The significant heterogeneity might be caused by statistical heterogeneity or other potential clinical diversity not included in the meta-regression. Q2: Does T2DM increase the risk of developing periodontitis? A total of 6 cohort studies were considered eligible. The results are summarized in Table 2. Two meta-analyses on periodontitis incidence were performed as follows. In addition to periodontitis incidence, other outcomes, including LOT, PPD, CAL and alveolar bone loss, were also reported. The results are summarized in Table 2. Four studies investigating whether manifested T2DM increases periodontitis incidence were included in one meta-analysis. In total, 46191 participants, including 2548 T2DM patients, were included, with a follow-up period ranging from 2.6 to 20 years. A total of 6361 incident periodontitis cases were detected. The results showed that T2DM led to a 34% elevated risk for incident PD (RR=1.34, 95% CI 1.11-1.61, p=0.002, Figure 3a). Slight heterogeneity among studies was detected (I 2 =54.7%, p=0.085). Influence analysis found that this result was stable (Figure S2a). Another meta-analysis was carried out to investigate the impact of well-controlled and poorly controlled T2DM on periodontitis incidence. In total, two studies with 2791 participants were included. Ninety-four well-controlled and 89 poorly controlled T2DM patients at the baseline were selected as the exposure group. The follow-up was 2.3 (1.2-6.9) and 5 years, respectively. Two included studies [23,69] both indicated that well-controlled T2DM did not increase the risk of periodontitis, and poorly controlled T2DM significantly promoted the incidence of periodontitis. The meta-analysis showed the same trend (Figure 3b), but the results were non-significant for both well-controlled T2DM (RR=1.22, 95% CI 0.63-2.39, p=0.548) and poorly controlled T2DM (RR=3.42, 95% CI 0.43-26.98, p=0.243). The non-significant result of the latter might be caused by a high level of heterogeneity (p=0.007; I²=86.3%). Q3: Does periodontitis increase the risk of developing T2DM? A total of 7 cohort studies were included. The results are summarized in Table 3. In total, 27498 participants were included. Among these participants, 8701 had mild periodontitis, while 3994 had severe periodontitis. A total of 1772 incident T2DM cases were detected during a follow-up period ranging from 5 to 18 years. Interestingly, all the included studies reported their results based on periodontitis severity. Thus, we performed two meta-analyses according to periodontitis severity as follows. The impact of mild periodontitis on T2DM incidence A meta-analysis on this topic showed that mild periodontitis led to a 28% elevated risk for incident T2DM (RR=1.28, 95% CI 1.07-1.54, p=0.007, Figure 4a). No significant heterogeneity (I 2 =20.4%, p=0.27) or publication bias (Egger, p=0.133; Begg, p=0.133) among studies was detected. Influence analysis found that this result was unstable (Figure S2b). Deleting Demmer’s study [63] would reduce the effect size and obtain a marginally significant result (RR=1.17, 95% CI 0.99-1.39, p>0.05). Due to this unstable result, we used the trim and fill method. After adding 3 hypothetical studies, the results became significant (RR=1.14, 95% CI 0.92-1.41, p=0.23, Table S5). The above results indicate that the effect of mild periodontitis on T2DM incidence was not very robust. The impact of severe periodontitis on T2DM incidence Pooled results showed that severe periodontitis increased the risk of T2DM incidence by 53% (RR= 1.53, 95% CI 1.27-1.83, p=0.000, Figure 4b). The heterogeneity was very low (I 2 =0%, p=0.649). No publication bias (Egger, p=0.104; Begg, p=0.230) was detected. In contrast to mild periodontitis, influence analysis found that the impact of severe periodontitis was very stable (Figure S2c). To further confirm this, we used the trim and fill method. After adding 2 hypothetical studies, the results were still significant (RR=1.46, 95% CI 1.23-1.73, p=0.000, Table S5). The above results indicated that the effect of severe periodontitis on T2DM incidence was strong. Discussion In this systematic review, we summarized observational studies exploring the bidirectional relationship between periodontitis and T2DM. Cross-sectional studies supported that there was a strong connection between periodontitis and T2DM. Prospective studies supported that T2DM and PD promoted the incidence of each other and were related to disease severity. The strength of our work mainly lies in including the most up-to-date evidence and analyzing sufficient studies and participants. However, the limitations of our work are also worth noting. For cross-sectional studies (Q1), high levels of heterogeneity existed among studies in 4 of our 6 meta-analyses. However, we did not find significant covariates that could decrease heterogeneity. Several reasons could partially explain the heterogeneity. First, these meta-analyses included a large number of studies, which would inevitably result in significant statistical diversity and cause statistical heterogeneity. Second, heterogeneity may result from measurement diversity. For example, the definitions of periodontitis were distinct, which could be based on a CPI code or clinical signs and symptoms. For CAL and PPD, measurement diversity was evident for the selection of teeth and probing sites. Third, the unreported confounding factors also caused heterogeneity. In contrast, in the 2 meta-analyses with limited heterogeneity based on adjusted ORs, the other 4 meta-analyses with high heterogeneity were all based on crude data. Few of the included studies reported confounding factors. This might partially explain why our meta-regression did not produce statistically significant results. For cohort studies, we summarized that T2DM and periodontitis promoted the incidence of each other. This bidirectional promotion phenomenon was closely related to the severity of the ailment. We found that T2DM patients with a poorly controlled glycemic state tended to have a higher risk of suffering from periodontitis compared to patients with better glycemic control. For patients with severe periodontitis, the incidence of T2DM was significantly higher compared to those with mild periodontitis. However, this conclusion was drawn from the subgroup analysis of a limited number of studies. To further confirm this, generalized least-squares trend estimation [72,73] or meta-regression should be used to evaluate this relationship. However, due to the inconsistency of exposure/outcome selection among limited studies, these analyses could not be performed. It is also worth noting that the same phenomenon was also revealed in the adjusted results of cross-sectional studies (Table 1) to a certain degree. Several important works, though notable, were not included in our study. Chiu’s study[62] and Joshipura’s study[74] found that periodontitis could increase the risk of developing prediabetes. Demmer’s study[75] found that periodontitis was associated with 5-year HbA1c progression. Additionally, in the present work, we did not include studies focusing on other aspects of the connection between periodontitis and T2DM. Very recently, the joint workshop between the European Federation of Periodontology and the International Diabetes Federation updated a systematic review on the effect of periodontitis on diabetes [76]. In contrast to our present study, which focused on whether periodontitis and T2DM were significantly correlated, this systematic review mainly focused on how periodontitis influences T2DM progression. The authors concluded that for T2DM patients, periodontitis is associated with higher levels of HbA1c and significantly worse diabetes-related complications. This article counters the limitations of our work to some degree, and the details are undeniably valuable. For future studies, several study design considerations should be considered. In our included studies, some researchers [21,30,34,37] defined their studies as case-control studies by mistake. The control group was age- and sex-matched with the cases; however, the cases (T2DM patients) were not newly diagnosed but were diagnosed years earlier. Both T2DM and periodontitis are chronic diseases that cannot be cured, and they might aggravate each other via positive feedback. Thus, once selected participants have suffered from T2DM for years, this relationship could become perplexing since their worsened periodontal health could be regarded as the cause of T2DM as well as the effect of T2DM. Therefore, the design of these studies should not be regarded as case-control; actually, they should be considered to have a case-matched cross-sectional design since one could not distinguish the onset time of T2DM or periodontitis. This is also relevant for cohort studies. Incident outcomes, especially T2DM, reported within 1 year of the baseline should be excluded to minimize the prevalence of undiagnosed baseline T2DM. [63,71] This also indicates that a longer follow-up period of cohort studies investigating these two diseases is required. As demonstrated by the included studies with adjusted results, the significant confounding factors in this bidirectional relationship included age, sex, body mass index, waist circumference, C-reactive protein, white blood cell count, hypertension, triglyceride, smoking status, education, income, frequency of dentist visits and other data. To deepen the knowledge of this bidirectional relationship between periodontitis and T2DM, we suggest that future observational studies should take these confounding factors into consideration. For researchers, these confounders should be recorded, described and analyzed in detail. In addition, there was a trend that this bidirectional relationship might be related to disease severity. Future studies could investigate these details and use subgroup or regression analysis. Based on the current available evidence, we concluded that periodontitis and T2DM had strong connections. Our findings suggest that dentists should be aware that periodontitis might indicate undiagnosed T2DM and poor glycemic control in T2DM patients; physicians should know the clinical signs of periodontitis to help T2DM patients improve their oral hygiene care and consider recommending periodontal therapy to improve glycemic control; patients should be aware that periodontitis and T2DM are risk factors for each other. Routine oral hygiene care and physical examinations are necessary for early prevention of T2DM or periodontitis. Declarations Ethics approval and consent to participate Not applicable. Consent to publish Not applicable. Availability of data and materials All data generated or analyzed during the present study are included in this published article. Competing interests The authors declare that they have no competing interests. Funding The work was supported by National Nature Science Foundation of China (81972538, 81672669), Key Technology R&D Program of Sichuan Province of China (2016SZ0063), and Graduate Student’s Research and Innovation Fund of Sichuan University (2018YJSY106). Authors' Contributions CZW, YHY, CJL and LJL designed the study. CZW, YHY, HHL, SSL, BWZ, WC, ZJA, SYC, YZW and BH extracted, analyzed, and interpreted the data. CZW and YHY drafted the manuscript. CZW, YHY and HHL review the manuscript. CZW, YHY, CJL and LJL revised the manuscript. All authors read and approved the final version of the manuscript. Acknowledgements Not applicable. 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Journal of clinical periodontology. doi:10.1111/jcpe.12774 Tables Table 1 Summary of adjusted results of cross-sectional studies Study Evaluated PD related conditions Definition of T2DM Main conclusion and outcome PD/non-PD Awuti 2012[20] Moderate PD: PPD ≤6 mm, or CAL of 3-4 mm; or possible presence of slight loose teeth (N=98) Severe PD: PPD >6 mm, or CAL ≥5 mm; or more than one loose tooth (N=77) Control: non-PD (N=509) The 1999 WHO criteria and ADA standards T2DM was more prevalent in moderate PD compared with no PD. Adjusted OR=4.033, 95%CI 2.069-7.861 T2DM was more prevalent in severe PD compared with no PD. Adjusted OR=2.313, 95%CI 1.042-5.137 Choi 2011[22] Top quintile category versus the bottom quintile CAL: Quintile 1 mean CAL=0.2mm (N=2412) Quintile 5 mean CAL=3.0mm (N=2453) ADA criteria T2DM was more prevalent in mean CAL 3.0mm compared with mean CAL 0.2mm. Adjusted OR=4.77, 95%CI 2.69–8.46 Top quintile category versus the bottom quintile PPD: Quintile 1 mean PPD=0.7mm (N=2451) Quintile 5 mean PPD=2.2mm (N=2449) T2DM was more prevalent in mean PPD 2.2mm compared with mean PPD 0.7mm. Adjusted OR=1.63, 95%CI 1.10–2.42 Mohamed 2013[37] Chronic PD: at least one site with PPD of >4mm (N=290) Control: non-PD (N=157) The 1999 WHO criteria T2DM was more prevalent in chronic PD compared with non-PD. Adjusted OR=4.07, 95%CI 1.74–9.49 Tooth mobility (N=153) Control: without tooth mobility (N=294) T2DM was more prevalent in participants with tooth mobility compared with those without. Adjusted OR=5.90, 95%CI 2.26–15.39 NOT >21 teeth (N=381) Control: NOT≤21 teeth (N=66) T2DM was less prevalent in participants with >21teeth, with an OR of 0.23. Adjusted OR=0.23, 95%CI 0.08–0.63 Nesse 2010[40] PD: CPITN score was ≥3, indicating PPD ≥4 mm (N=217) Control ： non-PD (N=320) Clinical examination; or medical record T2DM was more prevalent in PD compared with non-PD. Adjusted OR=4, 95%CI 1.03-15.3 Saito 2004[46] high portion category compared in the low portion CAL: Low mean CAL2.5mm (N=38) The WHO criteria T2DM was more prevalent in mean CAL >2.5mm compared with mean CAL 0.2mm. Adjusted OR=2.0, 95%CI 1.0-3.9 PPD: Low mean PPD2.0mm (N=32) T2DM was more prevalent in mean PPD >2.0mm compared with <1.3mm. Adjusted OR=2.6, 95%CI 1.3-5.0 Saito 2006[45] Mean alveolar bone loss (N=131) Control: Low alveolar bone loss (N=49) The WHO criteria Mean alveolar bone loss as a continuous variable showed a 1% increase in mean alveolar bone loss corresponded to a 6% increased prevalence of T2DM. Adjusted OR=1.06 95%CI 1.00-1.12 T2DM/non-T2DM Kaur 2009[25] Top quartile compared with three lower quartiles LOT (Quartile 4 vs 1-3) T2DM: After the age of 29; or insulin started >1 year after disease onset (N=310) Non-T2DM (N= 1858) The OR for increase tooth loss was 1.65 times higher for the T2DM patients compared with non-T2DM participants. Adjusted OR=1.65, 95%CI 1.13–2.39 Kowall 2015[27] PD: at least 2 non-adjacent teeth CAL≥3mm Poorly controlled T2DM ： HbA1c ≥7% (N=64) Better controlled T2DM ： HbA1c<7% (N=137) Non-T2DM (N=2145) PD was more prevalent in poorly controlled T2DM patients compared with non-T2DM participants, which was not statistically significant. Adjusted OR=1.60 95%CI 0.55-4.63 The prevalence of PD showed no difference between better controlled T2DM patients and non-T2DM participants. Adjusted OR=0.94 95%CI 0.52-1.67 Top quartile compared with three lower quartiles Mean CAL ≥ 4mm (Quartile 4 vs 1-3) The OR for CAL≥4mm was 1.36 times higher in poorly controlled T2DM patients compared with non-T2DM participants, which was not statistically significant. Adjusted OR=1.36 95%CI 0.75-2.49 The prevalence of CAL≥4mm showed no difference between better controlled T2DM patients and non-T2DM participants. Adjusted OR=0.94 95%CI 0.61-1.45 Top quartile compared with three lower quartiles Mean PPD (Quartile 4 vs 1-3) The OR for top PPD was 1.31 times higher for the poorly controlled T2DM patients compared with non-T2DM participants, which was not statistically significant. Adjusted OR=1.31 95%CI 0.75-2.30 The prevalence of mean PPD showed no difference between better controlled T2DM patients and non-T2DM participants. Adjusted OR=1.13 95%CI 0.75-1.71 Lowest quartile compared with three higher quartiles NOT (Quartile1 vs 2-4) The OR for NOT was 1.49 times higher in poorly controlled T2DM patients compared with non-T2DM participants, which was no statistically significant Adjusted OR=1.49 95%CI 0.92-2.40 NOT showed no difference between better controlled T2DM patients and non-T2DM participants. Adjusted OR=1.05 95%CI 0.74-1.50 Leung 2008[30] Chronic PD: CPI score of 4 in any one sextant (WHO, 1997). T2DM: Clinical examination; or medical record (N=364) Non-T2DM (N=161) PD was more prevalent in T2DM patients compared with non-T2DM participants. Adjusted OR= 1.84 95%CI 1.22-2.77 CAL≥ 6 mm The OR for CAL ≥ 6 mm was 1.71 times higher for T2DM patients compared with non-T2DM participants. Adjusted OR=1.71, 95%CI 1.13-2.59 Nelson 1990[39] PD: 6 teeth with ≥25% bone loss and any tooth with ≥50% bone loss. T2DM: OGTT ≥11.1mmol/l (N=720) Non-T2DM (N=1553) PD was more prevalent in T2DM patients compared with non-T2DM patients. Adjusted OR=1.64, 95%CI 1.50-1.79 Saito 2005[47] Mean PPD ≥1.9mm T2DM: The WHO criteria (N=27) Non-T2DM (N=360) The OR for PPD≥1.9mm was 1.4 times higher for the T2DM patients compared with non-T2DM participants, which was not statistically significant. Adjusted OR=1.4 95%CI 0.6-3.2 Mean CAL ≥2.42mm The OR for CAL≥2.42mm was 1.5 times higher for the T2DM patients compared with non-T2DM participants, which was not statistically significant. Adjusted OR=1.5 95%CI 0.7-3.2 Tanwir 2009[51] Missing fewer teeth T2DM: Clinical examination; or medical record (N=88) Non-T2DM (N=80) The OR for missing or fewer teeth was 2.3 times higher for the diabetic patients compared with non-T2DM patients. Adjusted OR=2.3 95%CI 1.32-4.14 Tsai 2002[52] Severe PD: at least two sites CAL ≥6mm at least one site PPD ≥5mm Poorly control T2DM ： HbA1c ≥9% (N=170) Better control T2DM ： HbA1c<9% (N=260) Non-T2DM (N=3841) Severe PD was more prevalent in poorly controlled T2DM patients compared with non-T2DM participants. Adjusted OR=2.90 95%CI 1.40-6.03 Severe PD was more prevalent in better controlled T2DM patients compared with non-T2DM participants, but was not statistically significant. Adjusted OR=1.56 95%CI 0.90-2.68 Wang 2009[53] PD: The WHO 1997 criteria T2DM: The 1999 WHO criteria (N=193) Non-T2DM (N=8468) PD was more prevalent in T2DM patients compared with non-T2DM participants. Adjusted OR=1.34 95%CI 1.07-1.74 PD: periodontitis; T2DM: type 2 diabetes mellitus; CAL: clinical attachment loss; PPD: periodontal pocket depth; NOT: number of teeth; LOT: loss of teeth; HbA1c: glycated haemoglobin; OR: odds ratio; CPI: community periodontal index; RPI: Russell periodontal index. Table 2 Summary of results of cohort studies Study Characteristics Definition of outcome Definition of exposure Main conclusion and outcome T2DM/non-T2DM Chiu 2015[62] Taiwan, KCIS study 5y FU (2003-2008) Binary variable PD: CPI≥3 Non-PD: CPI<3 T2DM: FBG≥126mg/dl or self-reported T2DM (N=57) Pre-diabetes: 100≤FBG<126 mg/dl (N=297) None: FBG<100mg/dl (N=4033) T2DM led to a 95% elevated risk for incident PD. Adjusted HR=1.95, 95%CI 1.22–3.13 Pre-diabetes led to a 25% elevated risk for incident PD. Adjusted HR=1.25, 95%CI 1.00–1.57 Demmer 2012[23] Germany, SHIP study 5y FU (1997-2006) Binary variable Tooth loss or not T2DM: Self-reported age>30 years old, or HbA1c≥6.5%, timing of insulin therapy initiation >1 year from diagnosis Controlled T2DM: HbA1c≤7% (N=80) Uncontrolled T2DM: HbA1c>7% (N=72) Control: no DM (N=2280) Controlled T2DM did not lead to an elevated risk for tooth loss. Adjusted RR=1.01, 95%CI 0.79–1.28 Uncontrolled T2DM led to a 36% elevated risk for tooth loss. Adjusted RR=1.36, 95%CI 1.11–1.67 Continuous variable Mean PPD change; Mean CAL change; Controlled T2DM did not lead to an increased PPD and CAL change. Adjusted MD=0.04 and 0.09 mm, p>0.05 Uncontrolled T2DM led to a significant increase in PPD and CAL change. Adjusted MD=0.18 and 0.37 mm, p<0.05 Jimenez 2012[65] USA, HPFS study, 20y FU (1986-NA) Binary variable PD: self-reported; Tooth loss: self-reported T2DM: self-reported T2DM (N=2285) Control: non-T2DM (N=32962) T2DM led to a 29% elevated risk for incident PD. Adjusted RR=1.29, 95%CI 1.13–1.47 T2DM led to a 9% elevated risk for incident tooth loss. Adjusted RR=1.09, 95%CI 1.01–1.18 Morita 2012[68] Japan, 5y FU (1997-2006) Binary variable PD: CPI≥3 Non-PD: CPI<3 T2DM: HbA1c≥6.5% (N=150) Control: HbA1c<6.5% (N=5706) T2DM led to a 17% elevated risk for incident PD. Adjusted RR=1.17, 95%CI 1.01–1.36 Nelson 1990[39] USA, Pima Indians study, Mean 2.6y FU (1983-1989) Binary variable PD: 6 teeth with ≥25% bone loss and any tooth with ≥50% bone loss. Non-PD: ≥24 teeth present; <6 could have 25-50% bone loss and the rest <25% bone loss T2DM: OGTT ≥ 11.1mM(N=56) Control: no T2DM (N=645) T2DM led to a 160% elevated risk for incident PD. Adjusted RR=2.57, 95%CI 1.0-6.6, p 75% Diagnosed by OGTT (>200mg/dl) Better controlled T2DM: HbA1c≥9% (N=7) Poorer controlled T2DM: HbA1c<9% (N=14) Control: no T2DM (N=338) Better controlled T2DM led to a 120% elevated risk for alveolar bone loss progression, but was not statistically significant. Adjusted OR=2.2, 95%CI 0.7–6.5, p=0.175 Poorer controlled T2DM led to a 1040% elevated risk for alveolar bone loss progression. Adjusted OR=11.4, 95%CI 2.5–53.3 PD/non-PD Demmer 2008[63] USA, NHEFS study 17y FU (1971-1992) T2DM: Death certificate; self-reported T2DM and received anti-diabetes medications; facility discharge diagnosis Category of baseline periodontal index, control group was the participants with lowest RPI score Compared to the control group, participants in the 1st or 2nd categories did not experience an increased OR of developing T2DM, whereas the odds increased sharply in the 3rd category (OR 2.08; P< 0.0001). The ORs in 4th (1.71; P=0.003) and 5th (1.50; P=0.06) categories abated but remained elevated and were not statistically significantly different from the odds for those in the 3rd category. PD: clinical diagnosed(N=1662) Gingivitis: clinical diagnosed (N=2135) Control: periodontium health (N=3372) PD led to a 50% elevated risk for incident T2DM. Adjusted OR≈1.50, 95%CI NA, p<0.05 Gingivitis led to a 40 % elevated risk for incident T2DM. Adjusted OR≈1.40, 95%CI NA, p<0.05 Exposure: LOT 25-31 (N=NA) Control: LOT 0-8 (N=NA) Loss more teeth at baseline led to a 70% elevated risk for incident T2DM. Adjusted OR≈1.70, 95%CI NA, p<0.05 Ide 2010[64] Japan, 6.3y FU (2000-2007) T2DM: FBG≥125mg/dl Exposure1: CPI=4 (N=490) Exposure2: CPI=3 (N=2167) Control: CPI<3 (N=3191) CPI=4 led to a 28% elevated risk for incident T2DM, but was not statistically significant. Adjusted HR=1.28, 95%CI 0.89–1.86 CPI=3 did not led to an elevated risk for incident T2DM. Adjusted HR=1.00, 95%CI 0.77–1.30 Exposure1: LOT>3 (N=748) Exposure2: 1<LOT<3 (N=2265) Control: LOT=0 (N=2835) Loss more than 3 teeth did not lead to an elevated risk for incident T2DM Adjusted HR=0.98 95%CI 0.69-1.39 Loss 1 or 2 teeth did not lead to an elevated risk for incident T2DM. Adjusted HR=1.02 95%CI 0.79-1.32 Kebede 2017[66] Germany, SHIP study 11.1y FU (1997-2012) T2DM: Self-reported physician diagnosed T2DM or treatment with antidiabetic medication Exposure: mean PPD 2.70–7.25mm (N=NA) Control: mean PPD 0.95–1.97 mm (N=NA) Deeper PPD did not lead to an elevated risk for incident T2DM. Adjusted incidence RR= 1.271 95% 0.782–2.065 Exposure: mean CAL 3.15-12.25mm (N=NA) Control: mean CAL 0–1.15mm (N=NA) Higher CAL did not lead to an elevated risk for incident T2DM. Adjusted incidence RR= 0.819 95%CI 0.489–1.370 Miyawaki 2016[67] Japan, My health up Study, all male 5y FU (2004-2009) T2DM: self-reported T2DM and received anti-diabetes medications, or based on clinical test (FBG≥126mg/dl or HbA1C≥6.5%) Exposure: self-reported tooth loosening (N=262) Control: without tooth loosening (N=2207) Tooth loosening led to a 73% elevated risk for incident T2DM. Adjusted RR=1.73, 95%CI 1.18–2.53 Exposure: self-reported gingival bleeding (N=795) Control: without gingival bleeding (N=1674) Gingival bleeding led to a 23% elevated risk for incident T2DM, but was not statistically significant. Adjusted RR=1.23, 95%CI 0.90–1.70 Morita 2012[68] Japan, 5y FU (1997-2006) T2DM: HbA1c≥6.5% Exposure1: CPI=4 (N=1634) Exposure2: CPI=3 (N=4114) Control: CPI=0 (N=1647) CPI=4 led to a 245% elevated risk for incident T2DM. Adjusted RR=3.45, 95%CI 1.08-11.02, p=0.037 CPI=3 led to a 145% elevated risk for incident T2DM, but was not statistically significant. Adjusted RR=2.47, 95%CI 0.78–7.79, p=0.122 Myllymki 2018[70] Finland, Cohort 1935 Survey, 15-18y FU (1990-2008) T2DM: WHO 1995 criteria Exposure1: PPD=4-5mm (N=98) Exposure2: PPD>6mm (N=91) Control: No deep pockets (N=88) Both two exposures did not increase the T2DM incidence. 4-5mm PPD: adjusted RR=1.32, 95%CI 0.69–2.53, p>0.05 >6mm PPD: adjusted RR=1.56, 95%CI 0.84–2.92, p>0.05 Winning 2016[71] UK, PRIME study 7.8y FU (2001-2010) T2DM: FBG≥126mg/dl and WHO criteria Exposure1: moderate PD Exposure2: severe PD Moderate/severe PD total=553 Control: No significant PD (N=778) PD severity was based on CDC/AAP classification Moderate PD led to a 53% elevated risk for developing T2DM, but was not statistically significant. Adjusted RR=1.53, 95%CI 0.86–2.74, p>0.05 Severe PD led to an 85% elevated risk for developing T2DM Adjusted RR=1.85, 95%CI 1.06–3.22, p<0.05 PD: periodontitis; T2DM: type 2 diabetes mellitus; CAL: clinical attachment loss; PPD: periodontal pocket depth; LOT: loss of teeth; OGTT: oral glucose tolerance test; HbA1c: glycated haemoglobin; FBG: fasting plasma glucose; CI: confidence intervals; OR: odds ratio; RR: risk ratios; HR: hazard ratio; CPI: community periodontal index; RPI: Russell periodontal index Supplementary File Legend Appendix Tables Appendix Table S1 Characteristics of the included cross-sectional studies Appendix Table S2 Characteristics of the included cohort studies Appendix Table S3 AHRQ scores of the cross-sectional studies Appendix Table S4 NOS scores of the included cohort studies Appendix Table S5 Summary of the trim and fill method Appendix Figures Appendix Figure S1 Influence analyses of cross-sectional studies (a) Results of adjusted ORs on T2DM prevalence (b) Results of adjusted ORs on periodontitis prevalence (c) Results of crude CAL (d) Results of crude PPD (e) Results of crude NOT (f) Results of crude LOT Appendix Figure S2 Influence analyses of cohort studies (a) The impact of T2DM on periodontitis incidence (b) The impact of mild periodontitis on T2DM incidence (c) The impact of severe periodontitis on T2DM incidence Supplementary Files supfig2.tif supfig1.tif supplementarytable.docx Cite Share Download PDF Status: Published Journal Publication published 11 Jul, 2020 Read the published version in BMC Oral Health → Version 2 posted Editorial decision: Minor revision 29 May, 2020 Review # 2 received at journal 19 May, 2020 Review # 1 received at journal 12 May, 2020 Reviewer # 1 agreed at journal 23 Apr, 2020 Reviewer # 2 agreed at journal 23 Apr, 2020 Reviewers invited by journal 22 Apr, 2020 Editor assigned by journal 29 Mar, 2020 Editor invited by journal 28 Mar, 2020 Submission checks completed at journal 24 Mar, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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2","display":"","copyAsset":false,"role":"figure","size":62837,"visible":true,"origin":"","legend":"Meta-analyses of cross-sectional studies. (a) Results of adjusted ORs on T2DM prevalence (b) Results of adjusted ORs on periodontitis prevalence (c) Results of crude CAL (d) Results of crude PPD (e) Results of crude NOT (f) Results of crude LOT","description":"","filename":"fig2.tif","url":"https://assets-eu.researchsquare.com/files/rs-1035/v2/fig 2.tif"},{"id":724167,"identity":"18200b88-9c5a-430d-b20d-9b7a47d06887","added_by":"auto","created_at":"2020-03-27 15:37:32","extension":"tif","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":20730,"visible":true,"origin":"","legend":"The impact of T2DM on periodontitis incidence. (a) Meta-analysis of periodontitis incidence (b) Meta-analysis of periodontitis incidence based on the level of glycemic control","description":"","filename":"fig3.tif","url":"https://assets-eu.researchsquare.com/files/rs-1035/v2/fig 3.tif"},{"id":724168,"identity":"08cbf4e7-babc-456b-b6b5-c590ee7026be","added_by":"auto","created_at":"2020-03-27 15:37:32","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":137175,"visible":true,"origin":"","legend":"The impact of periodontitis on T2DM incidence. (a) Meta-analysis based on mild periodontitis (b) Meta-analysis based on severe periodontitis","description":"","filename":"fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1035/v2/fig 4.jpg"},{"id":13496595,"identity":"e8347896-1369-4574-a862-60509649dff6","added_by":"auto","created_at":"2021-09-16 22:49:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":911546,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1035/v2/9fbe778a-d84d-43fb-a300-25a75589d8ca.pdf"},{"id":724166,"identity":"8af23549-dfe1-4a6f-a0b3-be7dac35e0b5","added_by":"auto","created_at":"2020-03-27 15:37:31","extension":"tif","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":7013682,"visible":true,"origin":"","legend":"","description":"","filename":"supfig2.tif","url":"https://assets-eu.researchsquare.com/files/rs-1035/v2/sup fig 2.tif"},{"id":724164,"identity":"b152174c-d91b-4fea-a1be-6765b40eeb73","added_by":"auto","created_at":"2020-03-27 15:37:31","extension":"tif","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":432520,"visible":true,"origin":"","legend":"","description":"","filename":"supfig1.tif","url":"https://assets-eu.researchsquare.com/files/rs-1035/v2/sup fig 1.tif"},{"id":724163,"identity":"3aa54876-484a-4fc2-901c-efd5f5c538d8","added_by":"auto","created_at":"2020-03-27 15:37:31","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":39371,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarytable.docx","url":"https://assets-eu.researchsquare.com/files/rs-1035/v2/supplementary table.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eEpidemiologic relationship between periodontitis and type 2 diabetes mellitus\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDiabetes mellitus (DM) is a common metabolic disease resulting from a defect in insulin secretion, a defect in insulin action or a combination of both [1]. Type 2 DM (T2DM) results from the body\u0026rsquo;s ineffective use of insulin and comprises 90% of people with DM worldwide [2]. The number of people with DM has risen rapidly in the last several decades from 108 million in 1980 to 422 million in 2014, and the number is likely to be more than double in the next 20 years. Furthermore, the WHO projected that diabetes will be the seventh leading cause of death in 2030 [3].\u003c/p\u003e\n\u003cp\u003ePeriodontitis is a chronic, multifactorial inflammatory disease in the underlying supporting tissues surrounding the teeth. Sufferers may experience gingivitis, loss of periodontal attachment, resorption of alveolar bone, and eventually tooth loss [4]. Severe periodontitis, which is the sixth most prevalent chronic disease among the general population, affects nearly 750 million people worldwide and is thought to affect people\u0026rsquo;s chewing ability, nutritional status and quality of life [5,6].\u003c/p\u003e\n\u003cp\u003eT2DM and periodontitis have a bidirectional relationship that is well documented in many reviews and epidemiological studies [7-9]. Periodontitis is defined as the sixth complication of DM, which means that DM can promote the progression of periodontitis [10]. Conversely, periodontitis is now known as a risk factor for worsening glycemic control and may increase the risk for diabetic complications [11]. Mechanistically, T2DM influences periodontitis initiation and progression by causing a hyperinflammatory response, impairing bone repair processes, and producing advanced glycation end products [9,12,13]. Periodontitis as a local focus of infection can cause the levels of IL-6, TNF-a, and CRP to increase in systems, resulting in increased systemic inflammation, which contributes to insulin resistance [14]. Based on the biological hypothesis, there are substantial randomized controlled trials (RCTs) that show periodontal treatment can improve glycemic control [15]. However, two well-designed large-scale RCTs obtained contradictory results on whether periodontal treatment had an effect on glycated hemoglobin (HbA1c) in T2DM patients [16,17].\u003c/p\u003e\n\u003cp\u003eThe above contradiction raised our curiosity. Do these two common diseases truly affect each other? However, after systematically searching the literature, we found that there was no systemic review to date that answers this question comprehensively. In the present work, we summarized evidence from observational studies to explore this bidirectional relationship.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003eThe protocol of the present systematic review was registered in PROSPERO (CRD42018089993). All procedures were performed following this protocol and in accordance with the MOOSE statements [18]. Two authors independently achieved study selection, quality assessment and data extraction. Any controversies were solved by consensus discussion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSearch strategy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe search strategy was a combination of an electronic search and a manual search. The manual search included the reference lists of the included studies and the following journals: Diabetes Care, Journal of Periodontology, Journal of Clinical Periodontology and Journal of Dental Research. The following electronic databases were searched without language limitations: MEDLINE (OVID, 1948 to December 2018), EMBASE (OVID, 1984 to December 2018), Chinese BioMedical Literature Database (CBM, 1978 to December 2018), and China National Knowledge Infrastructure (CNKI, 1994 to December 2018). MeSH terms with free text words were combined when conducting electronic searches. The MeSH terms used for PD were \u0026ldquo;periodontal diseases\u0026rdquo; and \u0026ldquo;periodontitis\u0026rdquo;. The free text word was \u0026ldquo;(periodont$ or gingivitis or gingiva$ or gum$).mp.\u0026rdquo;. The MeSH term used for T2DM searching was \u0026ldquo;diabetes mellitus, type 2\u0026rdquo;. Free text words were \u0026ldquo;(((non-insulin or noninsulin or type 2 or type II or matur$ or adult) adj4 (DM or diabet$)) or T2DM or DMT2 or NIDDM or MODY).mp.\u0026rdquo;. The titles and abstracts were initially scanned, and the full texts of the possibly eligible studies were obtained for final judgment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eObservational studies (cross-sectional studies, case-control studies and cohort studies) investigating the relationship between T2DM and PD were included. The criteria for the outcomes for periodontitis were clinical attachment loss (CAL), periodontal pocket depth (PPD), number of teeth (NOT), loss of teeth (LOT), alveolar bone loss and community periodontal index (CPI) score. The criteria for the outcomes for T2DM were oral glucose tolerance test (OGTT), HbA1c and fasting plasma glucose (FBG) results. Disease (periodontitis or T2DM) prevalence and incidence were also included. The participants chosen represent the natural population grouping into periodontitis versus non-periodontitis or T2DM versus non-DM. Comparisons based on periodontitis parameters, such as the T2DM incidence/prevalence between patients with low CAL levels and high CAL levels, were also included. Studies investigating outcomes in selected populations, such as comorbid patients, all periodontitis patients, all T2DM patients or all healthy participants (periodontitis-free and T2DM-free), were excluded. Studies were selected according to the aforementioned periodontitis/T2DM-related parameters, medical records or self-reported medical history.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodological quality assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study quality of cohort studies and case-control studies were measured by the Newcastle-Ottawa Scale (NOS) scoring system. Studies with scores less than 3 were regarded as low quality and were excluded. For cross-sectional studies, the Agency for Healthcare Research and Quality (AHRQ) scoring system was applied. Studies with scores less than 3 in the AHRQ scoring system were regarded as low quality and were not included.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData extraction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe extracted data were as follows: 1) investigator, 2) country, 3) number of participants, 4) age and sex of the participants, 5) recruitment of participants, 6) selected outcomes, and 7) NOS/AHRQ score. For cohort studies, the follow-up period and number of incident cases were also extracted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe software STATA 14.0 was utilized for meta-analysis. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated for continuous data. Odds ratios (ORs) and risk ratios (RRs) with 95% CIs were calculated for dichotomous data. Generic inverse variance (lnOR or lnRR) was used for meta-analyses that included studies that only reported ORs or RRs. Significance was determined by two-sided \u0026alpha; values with a cut-off p value of 0.05. All meta-analyses were performed under the random-effects model. Cochran\u0026rsquo;s Q test and I\u003csup\u003e2\u003c/sup\u003e statistic were used to detect statistical heterogeneity among studies. When P\u0026gt;0.10 and I\u003csup\u003e2\u003c/sup\u003e\u0026lt;50%, the study was regarded as having low heterogeneity; otherwise, it was regarded as having high heterogeneity. Meta-regression was utilized for a meta-analysis that included more than 4 studies to investigate possible sources of heterogeneity. The influence test was conducted by deleting every single study in turn to test whether the results were stable. For a meta-analysis that included more than 10 studies, publication bias was detected by Egger\u0026rsquo;s test and Begg\u0026rsquo;s test. The publication was excluded when both test results exhibited p\u0026gt;0.05. If publication bias existed or unstable results were found, the trim and fill method was applied.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eResults of \u003c/strong\u003e\u003cstrong\u003ethe \u003c/strong\u003e\u003cstrong\u003esearch and characteristics of \u003c/strong\u003e\u003cstrong\u003ethe \u003c/strong\u003e\u003cstrong\u003eincluded studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 1387 studies were identified from the primary search after removing duplicate studies. After screening the titles and abstracts, 73 studies were identified for further evaluation. After browsing the full text, 50 studies were considered eligible for inclusion. Twenty-three studies were excluded for various reasons. Among these, 16 studies were excluded because of the study type (7 meta-analyses, 6 review articles and 3 case series reporting periodontal treatment for T2DM patients); 4 studies were excluded because the reported outcomes were insufficient; 2 studies were excluded because they included type 1 DM. Additional reference checking revealed 3 studies that were then included. Journal searching did not add any new studies. Finally, a total of 53 studies were included in the present work. Figure 1 shows the search and inclusion process. Appendix Tables S1 and S2 summarize the characteristics of 43 [19-61] cross-sectional studies and 12 [62,23,63-68,39,69-71] cohort studies, respectively. Appendix Tables S3 and S4 summarize the AHRQ and NOS scores of cross-sectional studies and cohort studies. All included cross-sectional studies and cohort studies had scored higher than 3.\u003c/p\u003e\n\u003cp\u003eAfter systematically reviewing the included studies, we found that they answered 3 questions (questions 1-3, Q1-3). Specifically, cross-sectional studies gave the answer \u0026ldquo;Q1: Are periodontitis and T2DM associated with each other?\u0026rdquo; Cohort studies gave the answer to the other two questions: \u0026ldquo;Q2: Does T2DM increase the risk of developing periodontitis?\u0026rdquo;, and \u0026ldquo;Q3: Does periodontitis increase the risk of developing T2DM?\u0026rdquo;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults of meta-analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQ1: Are periodontitis and T2DM associated with each other?\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 43 cross-sectional studies were included to answer Q1. Evidence was from some national large-scale population-based studies, such as the SHIP, NHANES and KCIS, and some small-sample studies recruiting participants from communities or hospitals. Among these studies, only 14 studies reported adjusted outcomes (Table 1). Six meta-analyses were conducted as follows.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrength of association between periodontitis and T2DM\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 15 cross-sectional studies with 17924 participants reported the unadjusted OR between these two diseases (Table S1). Since the original data were not directionally adjusted, a meta-analysis was not undertaken. Among the 15 studies, except for 4 studies [21,34,43,51] that reported that the presence of periodontitis was not different between T2DM patients and non-T2DM controls, all the other studies acknowledged that there was a strong connection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDirectional adjusted T2DM prevalence (periodontitis versus \u003c/strong\u003e\u003cstrong\u003enonperiodontitis\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 6 cross-sectional studies were included, and all had T2DM prevalence as an outcome. Three studies with 1956 participants were included in a meta-analysis that included a periodontitis diagnosis as an outcome. The included studies had no significant heterogeneity. The results showed that periodontitis patients had significantly higher odds of T2DM prevalence than participants with no periodontitis (OR=4.04, 95% CI 2.48-6.59, p=0.000, Figure 2a). Influence analysis showed that the pooled result was stable (Figure S1a). Other exposure factors included CAL, PPD, LOT, tooth mobility and alveolar bone loss. The results all proved that T2DM was more prevalent in participants with worse periodontal health (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDirectional adjusted periodontitis prevalence \u003c/strong\u003e\u003cstrong\u003e(T2DM versus non-DM)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 8 cross-sectional studies were included, and all took T2DM as exposure. Three studies with 11459 participants were included in a meta-analysis evaluating periodontitis prevalence. No significant heterogeneity was detected. The results showed that T2DM patients had a significantly higher ORs for PD prevalence (OR=1.58, 95% CI 1.38-1.81, p=0.000, Figure 2b). Influence analysis indicated that the pooled result was stable (Figure S1b). In addition to periodontitis prevalence, other outcomes were divergent. In brief, all studies demonstrated that periodontitis-related parameters were more prevalent in T2DM patients, although some of the differences were not statistically significant. The results are summarized in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCAL level differences between T2DM and DM-free participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEighteen cross-sectional studies with 9571 participants were included. Significant heterogeneity was detected (p=0.000; I\u0026sup2;=92.5%). Pooled results showed that T2DM patients had a 0.89 mm higher CAL than controls (WMD=0.89, 95% CI 0.64-1.15, p=0.000, Figure 2c). Influence analysis demonstrated that the pooled result was stable (Figure S1c). Publication bias was detected by Egger\u0026rsquo;s and Begg\u0026rsquo;s tests (Egger, p=0.003; Begg, p=0.015). Then, we employed the trim and fill method to further evaluate publication bias and found that the results were still significantly positive after adding the hypothesized studies (Table S5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePPD differences between T2DM and DM\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003efree participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeventeen cross-sectional studies with 8982 participants were included. Significant heterogeneity was detected (P=0.000; I\u0026sup2;=94.5%). Pooled results showed that the periodontal pockets of T2DM patients were 0.61 mm deeper than those of controls (WMD=0.61, 95% CI 0.42-0.79, p=0.000, Figure 2d). Influence analysis demonstrated that the pooled result was stable (Figure S1d). Publication bias was detected by Egger\u0026rsquo;s and Begg\u0026rsquo;s test (Egger, p=0.015; Begg, p=0.006). However, adding hypothesized studies by the trim and fill method still resulted in strong significance (Table S5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNOT differences between T2DM and DM\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003efree participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNine cross-sectional studies with 4415 participants were included. Significant heterogeneity was detected (p=0.000; I\u0026sup2;=86.6%). Pooled results showed that T2DM patients had, on average, 2.01 fewer teeth remaining than controls. (WMD=-2.01, 95% CI -3.20--0.82, p=0.000, Figure 2e). Influence analysis demonstrated that the pooled result was stable (Figure S1e). No publication bias was detected (Egger, p=0.723; Begg, p=0.917).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLOT differences between T2DM and DM\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003efree participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEleven cross-sectional studies with 3405 participants were included. Significant heterogeneity was detected (P=0.000; I\u0026sup2;=90.7%). Pooled results showed that T2DM patients had, on average, lost 2.22 more teeth than controls. (MD=2.22, 95% CI 0.94-3.49, p=0.000, Figure 2f). Influence analysis demonstrated that the pooled result was stable (Figure S1f). No publication bias was detected (Egger, p=0.230; Begg, p=0.755).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeta-regression for meta-analyses with huge heterogeneity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHuge statistical heterogeneity existed in the above 4 meta-analyses, and the I\u003csup\u003e2\u003c/sup\u003e ranged from 86.3% to 94.5%; thus, we performed meta-regression to find the possible sources of heterogeneity. The available covariates included the number of participants, mean age, sex composition of the participants, geographic area and AHRQ scores. However, single variable regression did not find any significant covariates; multiple regression of these covariates only explained approximately 10% of the heterogeneity of all meta-analyses (data not shown). The significant heterogeneity might be caused by statistical heterogeneity or other potential clinical diversity not included in the meta-regression.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQ2: Does T2DM increase \u003c/strong\u003e\u003cstrong\u003ethe \u003c/strong\u003e\u003cstrong\u003erisk of developing periodontitis?\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 6 cohort studies were considered eligible. The results are summarized in Table 2. Two meta-analyses on periodontitis incidence were performed as follows. In addition to periodontitis incidence, other outcomes, including LOT, PPD, CAL and alveolar bone loss, were also reported. The results are summarized in Table 2.\u003c/p\u003e\n\u003cp\u003eFour studies investigating whether manifested T2DM increases periodontitis incidence were included in one meta-analysis. In total, 46191 participants, including 2548 T2DM patients, were included, with a follow-up period ranging from 2.6 to 20 years. A total of 6361 incident periodontitis cases were detected. The results showed that T2DM led to a 34% elevated risk for incident PD (RR=1.34, 95% CI 1.11-1.61, p=0.002, Figure 3a). Slight heterogeneity among studies was detected (I\u003csup\u003e2\u003c/sup\u003e=54.7%, p=0.085). Influence analysis found that this result was stable (Figure S2a).\u003c/p\u003e\n\u003cp\u003eAnother meta-analysis was carried out to investigate the impact of well-controlled and poorly controlled T2DM on periodontitis incidence. In total, two studies with 2791 participants were included. Ninety-four well-controlled and 89 poorly controlled T2DM patients at the baseline were selected as the exposure group. The follow-up was 2.3 (1.2-6.9) and 5 years, respectively. Two included studies [23,69] both indicated that well-controlled T2DM did not increase the risk of periodontitis, and poorly controlled T2DM significantly promoted the incidence of periodontitis. The meta-analysis showed the same trend (Figure 3b), but the results were non-significant for both well-controlled T2DM (RR=1.22, 95% CI 0.63-2.39, p=0.548) and poorly controlled T2DM (RR=3.42, 95% CI 0.43-26.98, p=0.243). The non-significant result of the latter might be caused by a high level of heterogeneity (p=0.007; I\u0026sup2;=86.3%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQ3: Does periodontitis increase\u003c/strong\u003e\u003cstrong\u003e the\u003c/strong\u003e\u003cstrong\u003e risk of developing T2DM?\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 7 cohort studies were included. The results are summarized in Table 3. In total, 27498 participants were included. Among these participants, 8701 had mild periodontitis, while 3994 had severe periodontitis. A total of 1772 incident T2DM cases were detected during a follow-up period ranging from 5 to 18 years. Interestingly, all the included studies reported their results based on periodontitis severity. Thus, we performed two meta-analyses according to periodontitis severity as follows.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe impact of mild periodontitis on T2DM incidence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA meta-analysis on this topic showed that mild periodontitis led to a 28% elevated risk for incident T2DM (RR=1.28, 95% CI 1.07-1.54, p=0.007, Figure 4a). No significant heterogeneity (I\u003csup\u003e2\u003c/sup\u003e=20.4%, p=0.27) or publication bias (Egger, p=0.133; Begg, p=0.133) among studies was detected. Influence analysis found that this result was unstable (Figure S2b). Deleting Demmer\u0026rsquo;s study [63] would reduce the effect size and obtain a marginally significant result (RR=1.17, 95% CI 0.99-1.39, p\u0026gt;0.05). Due to this unstable result, we used the trim and fill method. After adding 3 hypothetical studies, the results became significant (RR=1.14, 95% CI 0.92-1.41, p=0.23, Table S5). The above results indicate that the effect of mild periodontitis on T2DM incidence was not very robust.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe impact of severe periodontitis on T2DM incidence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePooled results showed that severe periodontitis increased the risk of T2DM incidence by 53% (RR= 1.53, 95% CI 1.27-1.83, p=0.000, Figure 4b). The heterogeneity was very low (I\u003csup\u003e2\u003c/sup\u003e=0%, p=0.649). No publication bias (Egger, p=0.104; Begg, p=0.230) was detected. In contrast to mild periodontitis, influence analysis found that the impact of severe periodontitis was very stable (Figure S2c). To further confirm this, we used the trim and fill method. After adding 2 hypothetical studies, the results were still significant (RR=1.46, 95% CI 1.23-1.73, p=0.000, Table S5). The above results indicated that the effect of severe periodontitis on T2DM incidence was strong.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this systematic review, we summarized observational studies exploring the bidirectional relationship between periodontitis and T2DM. Cross-sectional studies supported that there was a strong connection between periodontitis and T2DM. Prospective studies supported that T2DM and PD promoted the incidence of each other and were related to disease severity. The strength of our work mainly lies in including the most up-to-date evidence and analyzing sufficient studies and participants. However, the limitations of our work are also worth noting.\u003c/p\u003e\n\u003cp\u003eFor cross-sectional studies (Q1), high levels of heterogeneity existed among studies in 4 of our 6 meta-analyses. However, we did not find significant covariates that could decrease heterogeneity. Several reasons could partially explain the heterogeneity. First, these meta-analyses included a large number of studies, which would inevitably result in significant statistical diversity and cause statistical heterogeneity. Second, heterogeneity may result from measurement diversity. For example, the definitions of periodontitis were distinct, which could be based on a CPI code or clinical signs and symptoms. For CAL and PPD, measurement diversity was evident for the selection of teeth and probing sites. Third, the unreported confounding factors also caused heterogeneity. In contrast, in the 2 meta-analyses with limited heterogeneity based on adjusted ORs, the other 4 meta-analyses with high heterogeneity were all based on crude data. Few of the included studies reported confounding factors. This might partially explain why our meta-regression did not produce statistically significant results.\u003c/p\u003e\n\u003cp\u003eFor cohort studies, we summarized that T2DM and periodontitis promoted the incidence of each other. This bidirectional promotion phenomenon was closely related to the severity of the ailment. We found that T2DM patients with a poorly controlled glycemic state tended to have a higher risk of suffering from periodontitis compared to patients with better glycemic control. For patients with severe periodontitis, the incidence of T2DM was significantly higher compared to those with mild periodontitis. However, this conclusion was drawn from the subgroup analysis of a limited number of studies. To further confirm this, generalized least-squares trend estimation [72,73] or meta-regression should be used to evaluate this relationship. However, due to the inconsistency of exposure/outcome selection among limited studies, these analyses could not be performed. It is also worth noting that the same phenomenon was also revealed in the adjusted results of cross-sectional studies (Table 1) to a certain degree.\u003c/p\u003e\n\u003cp\u003eSeveral important works, though notable, were not included in our study. Chiu\u0026rsquo;s study[62] and Joshipura\u0026rsquo;s study[74] found that periodontitis could increase the risk of developing prediabetes. Demmer\u0026rsquo;s study[75] found that periodontitis was associated with 5-year HbA1c progression. Additionally, in the present work, we did not include studies focusing on other aspects of the connection between periodontitis and T2DM. Very recently, the joint workshop between the European Federation of Periodontology and the International Diabetes Federation updated a systematic review on the effect of periodontitis on diabetes [76]. In contrast to our present study, which focused on whether periodontitis and T2DM were significantly correlated, this systematic review mainly focused on how periodontitis influences T2DM progression. The authors concluded that for T2DM patients, periodontitis is associated with higher levels of HbA1c and significantly worse diabetes-related complications. This article counters the limitations of our work to some degree, and the details are undeniably valuable.\u003c/p\u003e\n\u003cp\u003eFor future studies, several study design considerations should be considered. In our included studies, some researchers [21,30,34,37] defined their studies as case-control studies by mistake. The control group was age- and sex-matched with the cases; however, the cases (T2DM patients) were not newly diagnosed but were diagnosed years earlier. Both T2DM and periodontitis are chronic diseases that cannot be cured, and they might aggravate each other via positive feedback. Thus, once selected participants have suffered from T2DM for years, this relationship could become perplexing since their worsened periodontal health could be regarded as the cause of T2DM as well as the effect of T2DM. Therefore, the design of these studies should not be regarded as case-control; actually, they should be considered to have a case-matched cross-sectional design since one could not distinguish the onset time of T2DM or periodontitis. This is also relevant for cohort studies. Incident outcomes, especially T2DM, reported within 1 year of the baseline should be excluded to minimize the prevalence of undiagnosed baseline T2DM. [63,71] This also indicates that a longer follow-up period of cohort studies investigating these two diseases is required.\u003c/p\u003e\n\u003cp\u003eAs demonstrated by the included studies with adjusted results, the significant confounding factors in this bidirectional relationship included age, sex, body mass index, waist circumference, C-reactive protein, white blood cell count, hypertension, triglyceride, smoking status, education, income, frequency of dentist visits and other data. To deepen the knowledge of this bidirectional relationship between periodontitis and T2DM, we suggest that future observational studies should take these confounding factors into consideration. For researchers, these confounders should be recorded, described and analyzed in detail. In addition, there was a trend that this bidirectional relationship might be related to disease severity. Future studies could investigate these details and use subgroup or regression analysis.\u003c/p\u003e\n\u003cp\u003eBased on the current available evidence, we concluded that periodontitis and T2DM had strong connections. Our findings suggest that dentists should be aware that periodontitis might indicate undiagnosed T2DM and poor glycemic control in T2DM patients; physicians should know the clinical signs of periodontitis to help T2DM patients improve their oral hygiene care and consider recommending periodontal therapy to improve glycemic control; patients should be aware that periodontitis and T2DM are risk factors for each other. Routine oral hygiene care and physical examinations are necessary for early prevention of T2DM or periodontitis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during the present study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe work was supported by National Nature Science Foundation of China (81972538, 81672669), Key Technology R\u0026amp;D Program of Sichuan Province of China (2016SZ0063), and Graduate Student\u0026rsquo;s Research and Innovation Fund of Sichuan University (2018YJSY106).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCZW, YHY, CJL and LJL designed the study. CZW, YHY, HHL, SSL, BWZ, WC, ZJA, SYC, YZW and BH extracted, analyzed, and interpreted the data. CZW and YHY drafted the manuscript. CZW, YHY and HHL review the manuscript. CZW, YHY, CJL and LJL revised the manuscript. All authors read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eState Key Laboratory of Oral Diseases \u0026amp; National Clinical Research Center for Oral Diseases \u0026amp; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eState Key Laboratory of Oral Diseases \u0026amp; National Clinical Research Center for Oral Diseases \u0026amp; Department of Orthognathic and Temporomandibular Joint Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China\u003c/p\u003e"},{"header":"Reference","content":"\u003col\u003e\n\u003cli\u003eBascones-Martinez A, Munoz-Corcuera M, Bascones-Ilundain J (2015) Diabetes and periodontitis: A bidirectional relationship. 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Journal of clinical periodontology 36 (9):765-774. doi:10.1111/j.1600-051X.2009.01445.x\u003c/li\u003e\n\u003cli\u003eKhader YS, Albashaireh ZSM, Hammad MM Periodontal status of type 2 diabetics compared with nondiabetics in north Jordan. East Mediterr Health J. 2008 May-Jun;14(3):654-61.,\u003c/li\u003e\n\u003cli\u003eKowall B, Holtfreter B, Volzke H, Schipf S, Mundt T, Rathmann W, Kocher T (2015) Pre-diabetes and well-controlled diabetes are not associated with periodontal disease: the SHIP Trend Study. Journal of clinical periodontology 42 (5):422-430. doi:10.1111/jcpe.12391\u003c/li\u003e\n\u003cli\u003eLan B, Liu Y (2012) The characteristics of periodontal disease in diabetic patients and its control measures. J Med Theor \u0026amp; Prac 25 (21):2667-2668[Chinese]\u003c/li\u003e\n\u003cli\u003eLeong P, Tumanyan S, Blicher B, Yeung A, Joshipura K (2007) Periodontal Disease among Adult, New-Immigrant, Chinese Americans in Boston with and without Diabetes ? A Brief Communication. 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Chin J Geriatr Dent 7 (1):17-19[Chinese]\u003c/li\u003e\n\u003cli\u003eSusanto H, Nesse W, Dijkstra PU, Agustina D, Vissink A, Abbas F (2011) Periodontitis prevalence and severity in Indonesians with type 2 diabetes. J Periodontol 82 (4):550-557. doi:10.1902/jop.2010.100285\u003c/li\u003e\n\u003cli\u003eTanwir F, Altamash M, Gustafsson A (2009) Effect of diabetes on periodontal status of a population with poor oral health. Acta Odontol Scand 67 (3):129-133. doi:10.1080/00016350802208406\u003c/li\u003e\n\u003cli\u003eTsai C, Hayes C, Taylor GW (2002) Glycemic control of type 2 diabetes and severe periodontal disease in the US adult population. Community Dent Oral Epidemiol 30 (3):182-192\u003c/li\u003e\n\u003cli\u003eWang TT, Chen TH, Wang PE, Lai H, Lo MT, Chen PY, Chiu SY (2009) A population-based study on the association between type 2 diabetes and periodontal disease in 12,123 middle-aged Taiwanese (KCIS No. 21). Journal of clinical periodontology 36 (5):372-379. doi:10.1111/j.1600-051X.2009.01386.x\u003c/li\u003e\n\u003cli\u003eWang X (2015) Analysis of periodontitis and dentition defect in elderly diabetic patients. Diabetes New World (Mar):106[Chinses]. doi:10.16658/j.cnki.1672-4062.2015.06.165\u003c/li\u003e\n\u003cli\u003eYuan K, Chang CJ, Hsu PC, Sun HS, Tseng CC, Wang JR (2001) Detection of putative periodontal pathogens in non-insulin-dependent diabetes mellitus and non-diabetes mellitus by polymerase chain reaction. Journal of Periodontal Research 36 (1):18-24\u003c/li\u003e\n\u003cli\u003eZhang H, Huang Y (2012) Analysis of the Relationship between Periodontal Tissue Disease and Type 2 Diabetes Mellitus. Prim Med 16 (16):2096-2097\u003c/li\u003e\n\u003cli\u003eZhang Y, Li H, Ren J (2013) The investigation on the Situation of periodontitis and Defect Dentition of Elder Men Patients with Diabetes Mellitus. Chin J Geriatr Dent 11 (5):281-283[Chinese]\u003c/li\u003e\n\u003cli\u003eZheng X (2016) A certain community of type 2 diabetes in patients with chronic periodontitis periodontal health survey. Cuide Chin Med 14 (16):11-12[Chinese]\u003c/li\u003e\n\u003cli\u003eZhou Y, Peng L, Liu H (2013) Clinical study on tooth loss and restoring and their related factors in patients with diabetes mellitus. Chin J New Clinical Med 6 (11):1046-1049[Chinese]\u003c/li\u003e\n\u003cli\u003eZielinski MB, Fedele D, Forman LJ, Pomerantz SC (2002) Oral health in the elderly with non-insulin-dependent diabetes mellitus. Special Care in Dentistry 22 (3):94-98\u003c/li\u003e\n\u003cli\u003eZou G (2014) The correlation and analysis of chronic periodontitis and type 2 diabetes mellitus. J Med Theor \u0026amp; Prac 27 (23):3225-3226[Chinese]\u003c/li\u003e\n\u003cli\u003eChiu SY, Lai H, Yen AM, Fann JC, Chen LS, Chen HH (2015) Temporal sequence of the bidirectional relationship between hyperglycemia and periodontal disease: a community-based study of 5,885 Taiwanese aged 35-44 years (KCIS No. 32). Acta Diabetol 52 (1):123-131. doi:10.1007/s00592-014-0612-0\u003c/li\u003e\n\u003cli\u003eDemmer RT, Jacobs DR, Jr., Desvarieux M (2008) Periodontal disease and incident type 2 diabetes: results from the First National Health and Nutrition Examination Survey and its epidemiologic follow-up study. Diabetes Care 31 (7):1373-1379. doi:10.2337/dc08-0026\u003c/li\u003e\n\u003cli\u003eIde R, Hoshuyama T, Wilson D, Takahashi K, Higashi T (2011) Periodontal disease and incident diabetes: a seven-year study. J Dent Res 90 (1):41-46. doi:10.1177/0022034510381902\u003c/li\u003e\n\u003cli\u003eJimenez M, Hu FB, Marino M, Li Y, Joshipura KJ (2012) Type 2 diabetes mellitus and 20 year incidence of periodontitis and tooth loss. Diabetes Res Clin Pract 98 (3):494-500. doi:10.1016/j.diabres.2012.09.039\u003c/li\u003e\n\u003cli\u003eKebede TG, Pink C, Rathmann W, Kowall B, Volzke H, Petersmann A, Meisel P, Dietrich T, Kocher T, Holtfreter B (2017) Does periodontitis affect diabetes incidence and haemoglobin A1c change? An 11-year follow-up study. Diabetes \u0026amp; metabolism. doi:10.1016/j.diabet.2017.11.003\u003c/li\u003e\n\u003cli\u003eMiyawaki A, Toyokawa S, Inoue K, Miyoshi Y, Kobayashi Y (2016) Self-Reported Periodontitis and Incident Type 2 Diabetes among Male Workers from a 5-Year Follow-Up to MY Health Up Study. 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Journal of clinical periodontology. doi:10.1111/jcpe.12774\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style=\"text-align: center; line-height: 150%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eTable 1 Summary of adjusted results of cross-sectional studies\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse: collapse; border: none;\" width=\"985\"\u003e\n\u003ctbody\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eStudy\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eEvaluated PD related conditions\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eDefinition of T2DM\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMain conclusion and outcome\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 738.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" colspan=\"4\" width=\"985\"\u003e\n\u003cp style=\"text-align: center; line-height: 150%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD/non-PD\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAwuti \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2012[20]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eModerate PD: PPD \u0026le;6 mm, or CAL of 3-4 mm; or possible presence of slight loose teeth (N=98)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eSevere PD: PPD \u0026gt;6 mm, or CAL \u0026ge;5 mm; or more than one loose tooth (N=77)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: non-PD (N=509)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe 1999 WHO criteria and ADA standards\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM was more prevalent in moderate PD compared with no PD.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted OR=4.033, 95%CI 2.069-7.861\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM was more prevalent in severe PD compared with no PD. \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted OR=2.313, 95%CI 1.042-5.137\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eChoi\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2011[22]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTop quintile category versus the bottom quintile\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eCAL: Quintile 1 mean CAL=0.2mm (N=2412)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eQuintile 5 mean CAL=3.0mm (N=2453)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" rowspan=\"2\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eADA criteria\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM was more prevalent in mean CAL 3.0mm compared with mean CAL 0.2mm. Adjusted OR=4.77, 95%CI 2.69\u0026ndash;8.46\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTop quintile category versus the bottom quintile\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePPD: Quintile 1 mean PPD=0.7mm (N=2451)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eQuintile 5 mean PPD=2.2mm (N=2449)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM was more prevalent in mean PPD 2.2mm compared with mean PPD 0.7mm. Adjusted OR=1.63, 95%CI 1.10\u0026ndash;2.42\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMohamed\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2013[37]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eChronic PD: at least one site with PPD of \u0026gt;4mm (N=290)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: non-PD (N=157)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" rowspan=\"3\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe 1999 WHO criteria\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM was more prevalent in chronic PD compared with non-PD. Adjusted OR=4.07, 95%CI 1.74\u0026ndash;9.49\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTooth mobility (N=153) \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: without tooth mobility (N=294)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM was more prevalent in participants with tooth mobility compared with those without. Adjusted OR=5.90, 95%CI 2.26\u0026ndash;15.39\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNOT \u0026gt;21 teeth (N=381)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: NOT\u0026le;21 teeth (N=66)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM was less prevalent in participants with \u0026gt;21teeth, with an OR of 0.23. Adjusted OR=0.23, 95%CI 0.08\u0026ndash;0.63\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNesse \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2010[40]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD:\u0026nbsp; CPITN score was \u0026ge;3, indicating PPD \u0026ge;4 mm (N=217)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl\u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; color: windowtext;\"\u003e：\u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003enon-PD (N=320)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eClinical examination;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eor medical record\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM was more prevalent in PD compared with non-PD. Adjusted OR=4, 95%CI 1.03-15.3\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eSaito\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2004[46]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ehigh portion category compared in the low portion\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eCAL: Low mean CAL\u0026lt; 1.5mm (N=18)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; High mean CAL\u0026gt;2.5mm (N=38)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" rowspan=\"2\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe WHO criteria\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM was more prevalent in mean CAL \u0026gt;2.5mm compared with mean CAL 0.2mm. Adjusted OR=2.0, 95%CI 1.0-3.9\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePPD:\u0026nbsp; Low mean PPD\u0026lt;1.3mm (N=18)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; High mean PPD\u0026gt;2.0mm (N=32)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM was more prevalent in mean PPD \u0026gt;2.0mm compared with \u0026lt;1.3mm. Adjusted OR=2.6, 95%CI 1.3-5.0\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eSaito\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2006[45]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMean alveolar bone loss (N=131)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: Low alveolar bone loss (N=49)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe WHO criteria\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMean alveolar bone loss as a continuous variable showed a 1% increase in mean alveolar bone loss corresponded to a 6% increased prevalence of T2DM. Adjusted OR=1.06 95%CI 1.00-1.12\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 738.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" colspan=\"4\" width=\"985\"\u003e\n\u003cp style=\"text-align: center; line-height: 150%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM/non-T2DM\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eKaur\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2009[25]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTop quartile compared with three lower quartiles\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eLOT (Quartile 4 vs 1-3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: After the age of 29; or insulin started \u0026gt;1 year after disease onset (N=310)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNon-T2DM (N= 1858)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe OR for increase tooth loss was 1.65 times higher for the T2DM patients compared with non-T2DM participants. Adjusted OR=1.65, 95%CI 1.13\u0026ndash;2.39\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eKowall \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2015[27]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD: at least 2 non-adjacent teeth CAL\u0026ge;3mm\u0026nbsp; \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" rowspan=\"4\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePoorly controlled T2DM\u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; color: windowtext;\"\u003e：\u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eHbA1c \u0026ge;7% (N=64)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eBetter controlled T2DM\u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; color: windowtext;\"\u003e：\u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eHbA1c\u0026lt;7% (N=137)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNon-T2DM (N=2145)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD was more prevalent in poorly controlled T2DM patients compared with non-T2DM participants, which was not statistically significant.\u0026nbsp; \u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: #231f20;\"\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted OR=1.60 95%CI 0.55-4.63\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe prevalence of PD showed no difference between better controlled T2DM patients and non-T2DM participants. Adjusted OR=0.94 95%CI 0.52-1.67\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTop quartile compared with three lower quartiles\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMean CAL \u0026ge; 4mm (Quartile 4 vs 1-3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe OR for CAL\u0026ge;4mm was 1.36 times higher in poorly controlled T2DM patients compared with non-T2DM participants, which was not statistically significant. Adjusted OR=1.36 95%CI 0.75-2.49\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe prevalence of CAL\u0026ge;4mm showed no difference between better controlled T2DM patients and non-T2DM participants. Adjusted OR=0.94 95%CI 0.61-1.45\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTop quartile compared with three lower quartiles\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMean PPD (Quartile 4 vs 1-3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe OR for top PPD was 1.31 times higher for the poorly controlled T2DM patients compared with non-T2DM participants, which was not statistically significant. Adjusted OR=1.31 95%CI 0.75-2.30\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe prevalence of mean PPD showed no difference between better controlled T2DM patients and non-T2DM participants. Adjusted OR=1.13 95%CI 0.75-1.71\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eLowest quartile compared with three higher quartiles \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNOT (Quartile1 vs 2-4)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe OR for NOT was 1.49 times higher in poorly controlled T2DM patients compared with non-T2DM participants, which was no statistically significant Adjusted OR=1.49 95%CI 0.92-2.40\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNOT showed no difference between better controlled T2DM patients and non-T2DM participants. Adjusted OR=1.05 95%CI 0.74-1.50\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eLeung \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2008[30]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eChronic PD: CPI score of 4 in any one sextant (WHO, 1997).\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" rowspan=\"2\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: Clinical examination; or medical record (N=364)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNon-T2DM (N=161)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD was more prevalent in T2DM patients compared with non-T2DM participants. Adjusted OR= 1.84 95%CI 1.22-2.77\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eCAL\u0026ge; 6 mm\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe OR for CAL \u0026ge; 6 mm was 1.71 times higher for T2DM patients compared with non-T2DM participants. Adjusted OR=1.71, 95%CI 1.13-2.59\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNelson\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e1990[39]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD: \u0026lt;24 teeth present;\u0026gt; 6 teeth with \u0026ge;25% bone loss and any tooth with \u0026ge;50% bone loss.\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: OGTT \u0026ge;11.1mmol/l (N=720)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNon-T2DM (N=1553)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD was more prevalent in T2DM patients compared with non-T2DM patients. Adjusted OR=1.64, 95%CI 1.50-1.79\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eSaito\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2005[47]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMean PPD \u0026ge;1.9mm\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" rowspan=\"2\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: The WHO criteria (N=27)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNon-T2DM (N=360)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe OR for PPD\u0026ge;1.9mm was 1.4 times higher for the T2DM patients compared with non-T2DM participants, which was not statistically significant. Adjusted OR=1.4 95%CI 0.6-3.2\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMean CAL \u0026ge;2.42mm\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe OR for CAL\u0026ge;2.42mm was 1.5 times higher for the T2DM patients compared with non-T2DM participants, which was not statistically significant. Adjusted OR=1.5 95%CI 0.7-3.2\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTanwir\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2009[51]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMissing fewer teeth \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: Clinical examination; or medical record (N=88)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNon-T2DM (N=80)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eThe OR for missing or fewer teeth was 2.3 times higher for the diabetic patients compared with non-T2DM patients. Adjusted OR=2.3 95%CI 1.32-4.14\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTsai\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2002[52]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eSevere PD: at least two sites CAL \u0026ge;6mm at least one site PPD \u0026ge;5mm \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePoorly control T2DM\u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; color: windowtext;\"\u003e：\u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eHbA1c \u0026ge;9% (N=170)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eBetter control T2DM\u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; color: windowtext;\"\u003e：\u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eHbA1c\u0026lt;9% (N=260)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNon-T2DM (N=3841)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eSevere PD was more prevalent in poorly controlled T2DM patients compared with non-T2DM participants. Adjusted OR=2.90 95%CI 1.40-6.03\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eSevere PD was more prevalent in better controlled T2DM patients compared with non-T2DM participants, but was not statistically significant. Adjusted OR=1.56 95%CI 0.90-2.68\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 14.7pt;\"\u003e\n\u003ctd style=\"width: 56.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"75\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eWang \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2009[53]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 205.0pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"273\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD: The WHO 1997 criteria\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156.5pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"209\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: The 1999 WHO criteria (N=193)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNon-T2DM (N=8468)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 320.8pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 14.7pt;\" width=\"428\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD was more prevalent in T2DM patients compared with non-T2DM participants. Adjusted OR=1.34 95%CI 1.07-1.74\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003ePD: periodontitis; T2DM: type 2 diabetes mellitus; CAL: clinical attachment loss; PPD: periodontal pocket depth; NOT: number of teeth; LOT: loss of teeth; HbA1c: glycated haemoglobin; OR: odds ratio; CPI: community periodontal index; RPI: Russell periodontal index.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 150%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eTable 2 Summary of results of cohort studies\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse: collapse; border: none; margin-left: 6.75pt; margin-right: 6.75pt;\" width=\"1018\"\u003e\n\u003ctbody\u003e\n\u003ctr style=\"height: .15in;\"\u003e\n\u003ctd style=\"width: 54.85pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: .15in;\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eStudy\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: .15in;\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eCharacteristics\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: .15in;\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eDefinition of outcome\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: .15in;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eDefinition of exposure\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: .15in;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMain conclusion and outcome\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 19.85pt;\"\u003e\n\u003ctd style=\"width: 763.8pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" colspan=\"5\" width=\"1018\"\u003e\n\u003cp style=\"text-align: center; line-height: 150%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM/non-T2DM\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 19.85pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eChiu\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2015[62]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTaiwan, \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eKCIS study\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e5y FU (2003-2008)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eBinary variable\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD: CPI\u0026ge;3\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNon-PD: CPI\u0026lt;3\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: FBG\u0026ge;126mg/dl or self-reported T2DM (N=57)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePre-diabetes: 100\u0026le;FBG\u0026lt;126 mg/dl (N=297)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNone: FBG\u0026lt;100mg/dl (N=4033)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM led to a 95% elevated risk for incident PD. Adjusted HR=1.95, 95%CI 1.22\u0026ndash;3.13\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePre-diabetes led to a 25% elevated risk for incident PD. Adjusted HR=1.25, 95%CI 1.00\u0026ndash;1.57\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 77.6pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 77.6pt;\" rowspan=\"2\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eDemmer 2012[23]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; padding: 0in 5.4pt 0in 5.4pt; height: 77.6pt;\" rowspan=\"2\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eGermany, \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eSHIP study\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e5y FU\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e(1997-2006)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 77.6pt;\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eBinary variable\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTooth loss or not \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 77.6pt;\" rowspan=\"2\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: Self-reported age\u0026gt;30 years old, or HbA1c\u0026ge;6.5%, timing of insulin therapy initiation \u0026gt;1 year from diagnosis\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControlled T2DM: HbA1c\u0026le;7% (N=80)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eUncontrolled T2DM: HbA1c\u0026gt;7% (N=72)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: no DM (N=2280)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 77.6pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControlled T2DM did not lead to an elevated risk for tooth loss.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted RR=1.01, 95%CI 0.79\u0026ndash;1.28\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eUncontrolled T2DM led to a 36% elevated risk for tooth loss. Adjusted RR=1.36, 95%CI 1.11\u0026ndash;1.67\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 77.6pt;\"\u003e\n\u003ctd style=\"width: 137.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 77.6pt;\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eContinuous variable\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMean PPD change; \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMean CAL change;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 77.6pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControlled T2DM did not lead to an increased PPD and CAL change. Adjusted MD=0.04 and 0.09 mm, p\u0026gt;0.05\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eUncontrolled T2DM led to a significant increase in PPD and CAL change. Adjusted MD=0.18 and 0.37 mm, p\u0026lt;0.05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 19.85pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eJimenez 2012[65]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eUSA, \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eHPFS study, \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e20y FU (1986-NA)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eBinary variable\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD: self-reported;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTooth loss: self-reported\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: self-reported T2DM (N=2285)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: non-T2DM (N=32962)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM led to a 29% elevated risk for incident PD. Adjusted RR=1.29, 95%CI 1.13\u0026ndash;1.47\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM led to a 9% elevated risk for incident tooth loss. Adjusted RR=1.09, 95%CI 1.01\u0026ndash;1.18\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 19.85pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMorita 2012[68]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eJapan,\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e5y FU (1997-2006)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eBinary variable\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD: CPI\u0026ge;3\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNon-PD: CPI\u0026lt;3\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: HbA1c\u0026ge;6.5% (N=150)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: HbA1c\u0026lt;6.5% (N=5706)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM led to a 17% elevated risk for incident PD. Adjusted RR=1.17, 95%CI 1.01\u0026ndash;1.36\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 19.85pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNelson 1990[39]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eUSA, \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePima Indians study, \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMean 2.6y FU\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e(1983-1989)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eBinary variable\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD: \u0026lt;24 teeth present;\u0026gt; 6 teeth with \u0026ge;25% bone loss and any tooth with \u0026ge;50% bone loss.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNon-PD: \u0026ge;24 teeth present; \u0026lt;6 could have 25-50% bone loss and the rest \u0026lt;25% bone loss\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: OGTT \u0026ge; 11.1mM(N=56)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: no T2DM (N=645)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM led to a 160% elevated risk for incident PD. Adjusted RR=2.57, 95%CI 1.0-6.6, p\u0026lt;0.05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 19.85pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTaylor\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e1998[69]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eUSA, Pima Indians study, \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMean 2.3y FU\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e(1.2-6.9 years)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMean alveolar bone loss \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ebone scores corresponded to bone loss of 0%, 1%to 24%, 25% to 49%, 50% to 74%, or \u0026gt; 75%\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eDiagnosed by OGTT (\u0026gt;200mg/dl)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eBetter controlled T2DM: HbA1c\u0026ge;9% (N=7)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePoorer controlled T2DM: HbA1c\u0026lt;9% (N=14)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: no T2DM (N=338)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eBetter controlled T2DM led to a 120% elevated risk for alveolar bone loss progression, but was not statistically significant. Adjusted OR=2.2, 95%CI 0.7\u0026ndash;6.5, p=0.175\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePoorer controlled T2DM led to a 1040% elevated risk for alveolar bone loss progression. Adjusted OR=11.4, 95%CI 2.5\u0026ndash;53.3\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 19.85pt;\"\u003e\n\u003ctd style=\"width: 763.8pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 19.85pt;\" colspan=\"5\" width=\"1018\"\u003e\n\u003cp style=\"text-align: center; line-height: 150%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD/non-PD\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 42.65pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 42.65pt;\" rowspan=\"3\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eDemmer 2008[63]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 42.65pt;\" rowspan=\"3\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eUSA, \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eNHEFS study\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e17y FU\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e(1971-1992)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 42.65pt;\" rowspan=\"3\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eDeath certificate; self-reported T2DM and received anti-diabetes medications; facility discharge diagnosis \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 42.65pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eCategory of baseline periodontal index, control group was the participants with lowest RPI score \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 42.65pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eCompared to the control group, participants in the 1st or 2nd categories did not experience an increased OR of developing T2DM, whereas the odds increased sharply in the 3rd category (OR 2.08; P\u0026lt; 0.0001). The ORs in 4th (1.71; P=0.003) and 5th (1.50; P=0.06) categories abated but remained elevated and were not statistically significantly different from the odds for those in the 3rd category.\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 7.25pt;\"\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD: clinical diagnosed(N=1662)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eGingivitis: clinical diagnosed (N=2135)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: periodontium health (N=3372)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD led to a 50% elevated risk for incident T2DM.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted OR\u0026asymp;1.50, 95%CI NA, p\u0026lt;0.05\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eGingivitis led to a 40 % elevated risk for incident T2DM.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted OR\u0026asymp;1.40, 95%CI NA, p\u0026lt;0.05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 7.25pt;\"\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure: LOT 25-31 (N=NA)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: LOT 0-8 (N=NA)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eLoss more teeth at baseline led to a 70% elevated risk for incident T2DM. Adjusted OR\u0026asymp;1.70, 95%CI NA, p\u0026lt;0.05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 7.25pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" rowspan=\"2\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eIde\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2010[64]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" rowspan=\"2\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eJapan, \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e6.3y FU\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e(2000-2007)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" rowspan=\"2\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eFBG\u0026ge;125mg/dl\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure1: CPI=4 (N=490)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure2: CPI=3 (N=2167)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: CPI\u0026lt;3 (N=3191)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eCPI=4 led to a 28% elevated risk for incident T2DM, but was not statistically significant.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted HR=1.28, 95%CI 0.89\u0026ndash;1.86\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eCPI=3 did not led to an elevated risk for incident T2DM. \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted HR=1.00, 95%CI 0.77\u0026ndash;1.30\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 7.25pt;\"\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure1: LOT\u0026gt;3 (N=748)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure2: 1\u0026lt;LOT\u0026lt;3 (N=2265)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: LOT=0 (N=2835)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eLoss more than 3 teeth did not lead to an elevated risk for incident T2DM\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted HR=0.98 95%CI 0.69-1.39\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eLoss 1 or 2 teeth did not lead to an elevated risk for incident T2DM. Adjusted HR=1.02 95%CI 0.79-1.32\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 7.25pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" rowspan=\"2\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eKebede\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e2017[66]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" rowspan=\"2\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eGermany, \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eSHIP study\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e11.1y FU\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e(1997-2012)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" rowspan=\"2\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eSelf-reported physician diagnosed T2DM or treatment with antidiabetic medication\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure: mean PPD 2.70\u0026ndash;7.25mm (N=NA)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: mean PPD 0.95\u0026ndash;1.97 mm (N=NA)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eDeeper PPD did not lead to an elevated risk for incident T2DM. \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted incidence RR= 1.271 95% 0.782\u0026ndash;2.065\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 7.25pt;\"\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure: mean CAL 3.15-12.25mm (N=NA)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: mean CAL 0\u0026ndash;1.15mm (N=NA)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eHigher CAL did not lead to an elevated risk for incident T2DM. \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted incidence RR= 0.819 95%CI 0.489\u0026ndash;1.370\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 7.25pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" rowspan=\"2\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMiyawaki 2016[67]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" rowspan=\"2\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eJapan, \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMy health up Study, \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eall male\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e5y FU\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e(2004-2009)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" rowspan=\"2\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: self-reported T2DM and received anti-diabetes medications, or based on clinical test (FBG\u0026ge;126mg/dl or HbA1C\u0026ge;6.5%)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure: self-reported tooth loosening (N=262)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: without tooth loosening (N=2207)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eTooth loosening led to a 73% elevated risk for incident T2DM.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;Adjusted RR=1.73, 95%CI 1.18\u0026ndash;2.53\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 7.25pt;\"\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure: self-reported gingival bleeding (N=795) \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: without gingival bleeding (N=1674)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eGingival bleeding led to a 23% elevated risk for incident T2DM, but was not statistically significant.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted RR=1.23, 95%CI 0.90\u0026ndash;1.70\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 7.25pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMorita 2012[68]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eJapan,\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e5y FU\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e(1997-2006)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: HbA1c\u0026ge;6.5%\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure1: CPI=4 (N=1634)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure2: CPI=3 (N=4114)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: CPI=0 (N=1647)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eCPI=4 led to a 245% elevated risk for incident T2DM.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted RR=3.45, 95%CI 1.08-11.02, p=0.037\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eCPI=3 led to a 145% elevated risk for incident T2DM, but was not statistically significant. \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted RR=2.47, 95%CI 0.78\u0026ndash;7.79, p=0.122\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 7.25pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eMyllymki 2018[70]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eFinland, Cohort 1935 Survey,\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e15-18y FU\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e(1990-2008)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: WHO 1995 criteria\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure1: PPD=4-5mm (N=98)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure2: PPD\u0026gt;6mm (N=91)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: No deep pockets (N=88)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eBoth two exposures did not increase the T2DM incidence.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e4-5mm PPD: adjusted RR=1.32, 95%CI 0.69\u0026ndash;2.53, p\u0026gt;0.05\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026gt;6mm PPD: adjusted RR=1.56, 95%CI 0.84\u0026ndash;2.92, p\u0026gt;0.05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 7.25pt;\"\u003e\n\u003ctd style=\"width: 54.85pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"73\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eWinning 2016[71]\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"100\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eUK,\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePRIME study\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e7.8y FU\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e(2001-2010)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 137.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"183\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eT2DM: FBG\u0026ge;126mg/dl and WHO criteria\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 184.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"246\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure1: moderate PD\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eExposure2: severe PD\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eModerate/severe PD total=553\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eControl: No significant PD (N=778)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003ePD severity was based on CDC/AAP classification\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 311.85pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"416\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eModerate PD led to a 53% elevated risk for developing T2DM, but was not statistically significant.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted RR=1.53, 95%CI 0.86\u0026ndash;2.74, p\u0026gt;0.05\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eSevere PD led to an 85% elevated risk for developing T2DM\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003eAdjusted RR=1.85, 95%CI 1.06\u0026ndash;3.22, p\u0026lt;0.05\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: windowtext;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003ePD: periodontitis; T2DM: type 2 diabetes mellitus; CAL: clinical attachment loss; PPD: periodontal pocket depth; LOT: loss of teeth; OGTT: oral glucose tolerance test; HbA1c: glycated haemoglobin; FBG: fasting plasma glucose; CI: confidence intervals; OR: odds ratio; RR: risk ratios; HR: hazard ratio; CPI: community periodontal index; RPI: Russell periodontal index\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Supplementary File Legend","content":"\u003cp\u003e\u003cstrong\u003eAppendix Tables\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAppendix Table S1 Characteristics of the included cross-sectional studies\u003c/p\u003e\n\u003cp\u003eAppendix Table S2 Characteristics of the included cohort studies\u003c/p\u003e\n\u003cp\u003eAppendix Table S3 AHRQ scores of the cross-sectional studies\u003c/p\u003e\n\u003cp\u003eAppendix Table S4 NOS scores of the included cohort studies\u003c/p\u003e\n\u003cp\u003eAppendix Table S5 Summary of the trim and fill method\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAppendix Figures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAppendix Figure S1 Influence analyses of cross-sectional studies (a) Results of adjusted ORs on T2DM prevalence (b) Results of adjusted ORs on periodontitis prevalence (c) Results of crude CAL (d) Results of crude PPD (e) Results of crude NOT (f) Results of crude LOT\u003c/p\u003e\n\u003cp\u003eAppendix Figure S2 Influence analyses of cohort studies (a) The impact of T2DM on periodontitis incidence (b) The impact of mild periodontitis on T2DM incidence (c) The impact of severe periodontitis on T2DM incidence\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Diabetes mellitus, type 2, Periodontitis, Systematic review, Meta-analysis, Epidemiologic Studies","lastPublishedDoi":"10.21203/rs.2.9843/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.9843/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003e To systematically review the epidemiologic relationship between periodontitis and type 2 diabetes mellitus (T2DM).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMaterials and Methods:\u003c/strong\u003e Four electronic databases were searched up until December 2018. The manual search included the reference lists of the included studies and relevant journals. Observational studies evaluating the relationship between T2DM and periodontitis were included\u003cstrong\u003e. \u003c/strong\u003eMeta-analyses were conducted using STATA.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e A total of 53 observational studies were included. The Adjusted T2DM prevalence was significantly higher in periodontitis patients (OR=4.04, p=0.000), and vice versa (OR=1.58, p=0.000). T2DM patients had significantly worse periodontal status, as reflected in a 0.61 mm deeper periodontal pocket, a 0.89 mm higher attachment loss and approximately 2 more lost teeth (all p=0.000), than those without T2DM. The results of the cohort studies found that T2DM could elevate the risk of developing periodontitis by 34% (p=0.002). The glycemic control of T2DM patients might result in different periodontitis outcomes. Severe periodontitis increased the incidence of T2DM by 53% (p=0.000), and this result was stable. In contrast, the impact of mild periodontitis on T2DM incidence (RR=1.28, p=0.007) was less robust.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e There is an evident bidirectional relationship between T2DM and periodontitis. Further well-designed cohort studies are needed to confirm this finding.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eClinical Relevance: \u003c/strong\u003eBoth dentists and physicians need to be aware of the strong connection between periodontitis and T2DM. Controlling these two diseases might help prevent each other’s incidence.\u003c/p\u003e","manuscriptTitle":"Epidemiologic relationship between periodontitis and type 2 diabetes mellitus","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2020-03-27 15:37:29","doi":"10.21203/rs.2.9843/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-05-29T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-05-19T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n\nComments to Author:\n---\nThe authors have answered my critique in an adequate way. I have no further comments.\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.**\n"},{"type":"editorInvitedReview","content":"","date":"2020-05-12T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n\nComments to Author:\n---\nPlease include all comments for the authors in this box rather than uploading your report as an attachment. Please only upload as attachments annotated versions of manuscripts, graphs, supporting materials or other aspects of your report which cannot be included in a text format.\nPlease overwrite this text when adding your comments to the authors.\nNo.* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"reviewerAgreed","content":"","date":"2020-04-23T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-04-23T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-04-22T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-03-29T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-03-28T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-03-24T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2019-05-28 12:58:15","doi":"10.21203/rs.2.9843/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-03-04T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-02-18T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nManuscript OHEA-D-19-00276\n\nThe purpose of this review is to explore the bidirectional relationship between Type 2 diabetes and periodontitis. I agree with the authors that this relationship has not been comprehensively summarized.\nI do, however, have some concerns.\n\nIntroduction\nThe introduction is good, just a couple of details:\nThe numbers in the third sentence of the third paragraph need a reference.\nReference number 14 could be replaced with Garziani et al. J Clin Periodontol. 2018 ;45:167-187. doi: 10.1111/jcpe.12837.\n\nMaterials and Methods\nThe description of the Materials and Methods is a bit unclear, such as the PD outcome. It is described as, among other variables, number of teeth and loss of teeth. These are not really a measure of PD. It does also say ….and so fourth…, which of course makes you curious, what can that be.\nThe last sentence a page 4 needs to be rephrased in order to clarify which studies were excluded and why they were excluded.\nIn general, the exclusions process needs to be explained better.\n\nResults\nThe findings are expressed in a clear way. Design to try to separate the association between the two diseases into the influence of T2DM om PD and vice versa.\n\nDiscussion\nThe discussion is interesting and well written but it is a bit focused on technicalities, I miss a reasoning around clinical implications. Are these findings of relevance for clinicians, within dentistry as well as within medicine, and patients?\n\n\nMy over all impression is that this is an interesting manuscript with pertinent findings.\n\n\n\n\n\n\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **Not relevant to this manuscript**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"reviewerAgreed","content":"","date":"2019-12-10T12:00:00+00:00","index":3,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-10-31T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-10-09T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nThis paper systematically reviewed the epidemiologic relationship between PD and T2DM, and revealed the bidirectional relationship between them. This manuscript was well conducted and logically fluent.\n\nAs what has been reported in this manuscript, in 2019, quite recently, the link between the two diseases were also systematically reviewed in another paper, which weakened the degree of innovation of this present work. I suggest the author further explain the difference of methods and/ or results of this two work.\n\nAnd some mistakes in grammar and spelling should be commended after a careful check.\n1. For example, in the introduction part, page3, line36, \"PD initial and progression\", \"initial\" had better be replaced by \"initiate\".\n2. There were no detailed quality assessments of the original literature, please supplement.\n3. We select analytical model according to the heterogeneity test, not the number of included studies. Besides, in view of individual difference in clinical study, random-effect model is usually used. See the 36th and 37th in page 5.\n4. It's not reasonable in statistics that all the cross-sectional studies could be analyzed together without considering the direction of original study, so result---Strength of association between PD and T2DM should be deleted.\n5. Generally, PD is the abbreviation of periodontal disease, not periodontitis. Please amend. Besides, there were no without full titles of NOT and LOT in the first time, so what are the meaning of them.\n6. The source of significant heterogeneity might be caused by statistical heterogeneity and clinical diversity other than excessive number of included studies, see the line 33th in page 8.\n7. There is a false description in this sentence \"mild PD led to a 28% elevated risk for incident PD\".\n8. How could you conduct this conclusion that \"T2DM and PD promoted the incidence of each other in a dose-dependent way\"? There was no direct evidence of it in this study. Please state this in detail.\n9. There was ambiguous of this item \"Articles excluded (n=23)\" in Figure 1, please amend.\n\n\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"reviewerAgreed","content":"","date":"2019-09-18T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorAssigned","content":"","date":"2019-06-02T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2019-06-02T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-05-22T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-05-20T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2019-05-09T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"19ba3fe7-2323-4a6b-a824-7231ff3f528f","owner":[],"postedDate":"March 27th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":12785,"name":"Dentistry"},{"id":12786,"name":"Epidemiology"}],"tags":[],"updatedAt":"2020-07-12T15:01:21+00:00","versionOfRecord":{"articleIdentity":"rs-1035","link":"https://doi.org/10.1186/s12903-020-01180-w","journal":{"identity":"bmc-oral-health","isVorOnly":false,"title":"BMC Oral Health"},"publishedOn":"2020-07-11 12:00:00","publishedOnDateReadable":"July 11th, 2020"},"versionCreatedAt":"2020-03-27 15:37:29","video":"","vorDoi":"10.1186/s12903-020-01180-w","vorDoiUrl":"https://doi.org/10.1186/s12903-020-01180-w","workflowStages":[]},"version":"v2","identity":"rs-1035","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-1035","version":["v2"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}