糖尿病与牙周炎的双向流行病学关联与临床特征：危险因素、糖尿病类型、代谢控制水平与牙周疾病易感性及严重程度的相关性

… The association between the two diseases is bidirectional, as … of periodontal diseases are described. This Review also covers the role of diabetes mellitus as a risk factor for periodontitis…

Periodontitis and diabetes are two major global health problems despite their prevalence being significantly underreported and underestimated. Both epidemiological and intervention studies show a bidirectional relationship between periodontitis and diabetes. The hypothesis of a potential causal link between the two diseases is corroborated by recent studies in experimental animals that identified mechanisms whereby periodontitis and diabetes can adversely affect each other. Herein, we will review clinical data on the existence of a two-way relationship between periodontitis and diabetes and discuss possible mechanistic interactions in both directions, focusing in particular on new data highlighting the importance of the host response. Moreover, we will address the hypothesis that trained immunity may represent the unifying mechanism explaining the intertwined association between diabetes and periodontitis. Achieving a better mechanistic insight on clustering of infectious, inflammatory, and metabolic diseases may provide new therapeutic options to reduce the risk of diabetes and diabetes-associated comorbidities.

BACKGROUND Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. The abnormal glucose metabolism results from defects in insulin production or insulin action, or both. For decades, it was suspected that diabetes contributed to poorer oral health and the increased frequency of periodontitis. More recently it was found that periodontitis could adversely affect glycemic control in diabetics. This review focuses on the bidirectional relationship between diabetes mellitus and periodontitis. METHODS AND RESULTS A review of the literature on periodontal disease in diabetes using the following key words: periodontitis/periodontal disease and diabetes mellitus, hyperglycemia/glycemic control. CONCLUSIONS There is strong evidence for an association between diabetes mellitus and inflammatory periodontal disease. Diabetes mellitus increases the risk for and severity of periodontitis, and periodontal diseases can aggravate insulin resistance and affect glycemic control. Periodontal treatment improves glycemic control in type 2 diabetics; control of periodontal infection is not only important for oral health, it may also improve overall health.

Periodontitis and diabetes mellitus are two prevalent chronic diseases that have been recognized to exhibit a bidirectional relationship. Individuals with diabetes are more susceptible to periodontitis, and conversely, periodontitis can exacerbate glycemic control in diabetic patients. The underlying mechanisms of this interrelationship involve complex pathways, including inflammatory responses, altered immune functions, and microbial dysbiosis. The mechanistic insights into the interrelationship between periodontitis and diabetes mellitus revolve around the role of inflammation as a common link between the two diseases. Inflammatory mediators such as cytokines, chemokines, and prostaglandins play a crucial role in the pathogenesis and progression of the diseases. The dysregulation of the immune response in diabetes can exacerbate the inflammatory response in periodontitis, leading to increased tissue destruction and bone resorption. The chronic inflammation in periodontitis can contribute to insulin resistance and impaired glycemic control in diabetic patients. Future directions in research aim to further elucidate the molecular mechanisms underlying the interrelationship between periodontitis and diabetes mellitus. Modulating the inflammatory response, restoring microbial balance, and improving glycemic control hold promise in managing both conditions simultaneously. Herein, we will provide an overview of the interrelationship of periodontitis and diabetes mellitus, and retrospect the underlying mechanisms, which may inspire investigators with further research directions.

… on the bidirectional link between periodontitis and diabetes. Three questions were asked: (1) … is the effect of diabetes on periodontitis?, (2) what is the effect of periodontitis on diabetes?, …

… associations, the link between periodontitis and diabetes mellitus stands out due to its strong bidirectional … and exacerbates periodontal tissue destruction, while periodontitis itself may …

The objective of this study is to analyze the miRNA expression of oral fluids such as gingival crevicular fluid (GCF) in patients with periodontitis and Type 2 diabetes mellitus, and how these epigenetic biomarkers can influence the bidirectional relationship of these two inflammatory diseases. This review was conducted following the PRISMA criteria. PubMed, Scopus, Cochrane Library, Embase, and Web of Science databases were searched for clinical studies conducted on humans investigating, through GCF miRNA expression, the relationship between periodontal diseases and type 2 diabetes mellitus. In addition, the etiopathogenic pathways of the studied miRNAs were analyzed using the DIANA MIR path tool. A total of 1436 references were identified in the initial literature search, and seven articles were finally included in this review. Most of the articles included in this review were case–control studies and examined the expression of miRNAs in patients with periodontitis with or without diabetes. Due to their characteristics, miRNAs appear to be the ideal biomarkers for improving the understanding and knowledge of the etiopathogenic pathways that link both diseases. Among all the studied miRNAs, miR-146a, miR-155, miR-200b, miR-223, and miR-203 showed strong involvement in inflammatory and metabolic pathways, making them potential good diagnostic and prognostic biomarkers.

… Paradigms for bidirectional relationships between periodontitis and diabetes are discussed … pathways which support a close association between diabetes and periodontitis, but there is …

AIM This study investigated the existence of a bidirectional temporal relationship between periodontal condition and glycemic status. MATERIALS AND METHODS This longitudinal study included 2,198 participants with mean age 43.4±7.7 years, who underwent dental examinations in Yokohama, Japan at two-time points, 2003-2004 and 2008-2009, at an interval of five years. Periodontal condition was assessed by the mean value of probing pocket depth (PPD) and clinical attachment level (CAL). Glycemic status was assessed by fasting glucose and glycated hemoglobin (HbA1c). RESULTS The cross-lagged panel models showed the effect of HbA1c at baseline on mean PPD at follow-up was found (β = 0.044, p = 0.039). There was a marginally effect of fasting glucose on mean PPD (β = 0.037, p = 0.059). It was similar to the effect of fasting glucose or HbAlc on mean CAL. However, in the opposite direction, the effect of mean PPD or CAL at baseline on fasting glucose or HbAlc at follow-up was not identified. CONCLUSION This study demonstrated a unidirectional relationship between glycemic status and periodontal condition. This study population has mostly mild periodontitis. Future studies are needed to investigate the effect of periodontal condition on glycemic status in patients with severe periodontitis. This article is protected by copyright. All rights reserved.

Insulin resistance (IR) is now considered as a chronic and low level inflammatory condition. It is closely related to altered glucose tolerance, hypertriglyceridemia, abdominal obesity, and coronary heart disease. IR is accompanied by the increase in the levels of inflammatory cytokines like interleukin-1 and 6, tumor necrosis factor-α. These inflammatory cytokines also play a crucial part in pathogenesis and progression of insulin resistance. Periodontitis is the commonest of oral diseases, affecting tooth investing tissues. Pro-inflammatory cytokines are released in the disease process of periodontitis. Periodontitis can be attributed with exacerbation of IR. Data in the literature supports a "two way relationship" between diabetes and periodontitis. Periodontitis is asymptomatic in the initial stages of disease process and it often escapes diagnosis. This review presents the blurred nexus between periodontitis and IR, underlining the pathophysiology of the insidious link. The knowledge of the association between periodontitis and IR can be valuable in planning effectual treatment modalities for subjects with altered glucose homeostasis and diabetics. Presently, the studies supporting this association are miniscule. Further studies are mandatory to substantiate the role of periodontitis in the deterioration of IR.

ABSTRACT Diabetes mellitus and periodontal disease are among the most frequently occurring conditions that have a substantial effect on the global health economy. The literature regarding medical professionals’ knowledge of the bidirectional link between diabetes mellitus and periodontal disease has not been analyzed systematically. The review aimed to investigate the knowledge and understanding of physicians and specialists regarding the two-way relationship between diabetes mellitus and periodontal disease and their approach to referring their patients for a dental consultation. An electronic search of PubMed and Google Scholar databases was conducted to review the studies that assessed knowledge and understanding of medical professionals regarding the relationship between diabetes mellitus and periodontal disease. Data from 13 included studies involved 4,027 participants: 3,256 primary care physicians and 771 medical specialists. Just over 50% of the medical professionals had an understanding of oral health and/or periodontal disease. Over one-third of medical professionals were ignorant of the relationship between oral health and diabetes mellitus. Only 30% reported ever referring their patients for an oral health assessment. Another key finding of the investigation was the absence of interprofessional collaborative care between medical and dental professionals while managing patients with diabetes mellitus. Medical professionals with an integrated knowledge of elementary oral health education and training could play a central role in the timely diagnosis and management of periodontal disease in patients living with diabetes mellitus.

To evaluate the associations of periodontal disease (PD) with systemic diseases, including diabetes mellitus (DM) and cardiovascular disease (CVD), as well as the reciprocal association. The CVD included the cases of coronary heart disease and heart failure. A prospective study was conducted from 2007 to 2019 using linked data from three databases in Korea. Three separate study groups were formed to individually determine the risks of PD (n = 10,533), DM (n = 14,523) and CVD (n = 14,315). All diseases were confirmed based on physicians’ diagnoses using medical records and self-reports. Cox proportional hazard regression was applied with 95% confidence intervals (CIs) to obtain hazard ratios (HRs). PD was significantly associated with an elevated risk of DM (HR [95% CI]: 1.22 [1.07–1.39]) after full adjustment for age, sex, lifestyle factors, body mass index, dental behaviour and CVD. PD was also found to increase the risk of CVD (1.27 [1.03–1.57]), whereas CVD increased the risk of PD (1.20 [1.09–1.32]) after full adjustment for other covariates including DM. This study found a bidirectional association between PD and CVD, as well as a positive association of PD with DM.

BackgroundDiabetes mellitus (DM) and periodontitis are very common and they interact with each other bidirectionally. This survey studied public primary care doctors on their awareness of this bidirectional relationship and their corresponding practice.MethodsAll Family Medicine doctors in Kowloon West Cluster, Hospital Authority were invited to a cross-sectional questionnaire survey. Results were analyzed statistically.ResultsOne hundred sixty-eight questionnaires were sent out, 143 were returned (response rate 85.1%). One hundred forty valid questionnaires were analyzed. Ninety-two percent of participants were aware of a relationship between DM and periodontal disease and this awareness was not associated with their years of experience, training status and personal oral health behavior. Ninety percent knew the effect of poor DM control on periodontal disease but only 76% were aware of the reverse effect of periodontal disease on DM. The difference was statistically significant (p = 0.002, Related-samples Sign Test). In clinical practice on DM patients, only 5.7% asked dental history often (defined as 50% patients or above), 7.1% examined their mouths often and 12.1% recommended them to see dentist often. Logistic regression showed that awareness factors had no association with periodontology related clinical practice whereas clinical experience, being a Family Medicine specialist and personal interdental cleaning habit were linked with more positive practice.ConclusionsA high proportion of doctors in the study were aware of the relationship between DM and periodontal disease. However, this did not appear to influence their practice. Further measures among doctors and patients to promote comprehensive management of DM and periodontal disease should be explored.

Diabetes mellitus is a group of metabolic disorders with high mortality and morbidity associated with complications such as cardiovascular disease, kidney disease, and stroke. The prevalence of diabetes is 9.4% in US adults, and prevalence increases markedly with age, with 1 in 4 adults aged ≥65 years affected by diabetes. The estimated number of adults with type 2 diabetes globally almost tripled between 2002 and 2017, reflecting increases seen in the USA and elsewhere. This increase raises concerns about the increased morbidity and mortality associated with the complications of diabetes, including periodontal disease and tooth loss. There is a reciprocal adverse relationship between diabetes and periodontal disease, with diabetes as a major risk factor for periodontal disease, and in those patients with diabetes who also have periodontal disease then there are adverse effects on glycemic control and complications such as cardiovascular disease and end stage renal disease. In this review, those studies detailing the adverse effects of periodontal disease and diabetes will be discussed. Also, evidence is accumulating that periodontitis may play a role in increasing the incidence of new cases of type 2 diabetes, and possibly gestational diabetes. Of course, these studies need to be expanded to better understand the effects of periodontitis on diabetes glycemic control, complications, prediabetes, and the incidence of new cases. However, given the tremendous burden of diabetes on society, the dental profession should be proactive in preventing and treating periodontal disease, not only to preserve the dentition, but also to minimize the adverse effects of periodontitis on diabetes and its complications.

… Hb1AC levels Age, diabetes mellitus, periodontal pocket depth, … of periodontal visits OR [95% CI] of prevalence of pancreatic cancer in subjects with diabetes and periodontal disease …

… DM and periodontitis, and periodontal treatment is not used as a method of controlling blood glucose in diabetic patients according to the latest guidelines for the treatment of DM [18, 19]…

Periodontitis is a chronic inflammatory disease, initiated by the presence of a bacterial biofilm, called dental plaque, which affects both the periodontal ligaments and bone surrounding teeth. In the last decades, several lines of evidence have supported the existence of a relationship between periodontitis and systemic health. For instance, as periodontitis acts within the same chronic inflammatory model seen in cardiovascular disease (CVD), or other disorders, such as diabetes, several studies have suggested the existence of a bi-directional link between periodontal health and these pathologies. For instance, people with diabetes are more susceptible to infections and are more likely to suffer from periodontitis than people without this syndrome. Analogously, it is now evident that cardiac disorders are worsened by periodontitis, both experimentally and in humans. For all these reasons, it is very plausible that preventing periodontitis has an impact on the onset or progression of CVD and diabetes. On these grounds, in this review, we have provided an updated account on the current knowledge concerning periodontal disease and the adverse effects exerted on the cardiovascular system health and diabetes, informing readers on the most recent preclinical studies and epidemiological evidence.

… Diabetes mellitus affects an estimated 20 million … diabetes and periodontitis used over the years; varying clinical and radiographic criteria used to assess periodontal disease prevalence…

… Several studies have been published regarding a possible association between diabetes mellitus and periodontal disease. The findings reported, however, are contradictory. Thus, in …

… Because infections and inflammatory reactions often increase the insulin requirements of previously stable patients who have diabetes, this study of periodontal infections in young …

Periodontal disease and poorly or uncontrolled diabetes adversely affect each other: (i) hyperglycemia increases the risk for and severity of periodontal disease, and (ii) periodontitis contributes to hyperglycemia and diabetes complications. Persons with diabetes have greater tooth loss, which in turn leads to dietary changes that can adversely affect diabetes control. Routine, nonsurgical periodontal treatment can lead to a statistically significant reduction in HbA1c level in patients with poorly controlled type 2 diabetes. This reduction is of an effect similar to adding a second medication to metformin. Hence, management of periodontal disease represents another option in the management of diabetes in patients with poor glycemic control. Dentists are willing to screen for diabetes in their practices, and such screening is shown to detect previously undiagnosed diabetes and identify those at risk for hyperglycemia. Co-management of both those chronic diseases would be beneficial for both individuals and society. The time has come for interprofessional collaboration in patient-centered healthcare teams to optimize management of diabetes and its complications, including periodontal disease.

Background Few studies have specifically examined the relationship between periodontal disease and gestational diabetes mellitus (GDM). The objective of this study was to examine whether maternal periodontal disease is associated with GDM. Methods A case-control study was conducted of 53 pregnant women with GDM and 106 pregnant women without GDM at Woman’s Hospital, Baton Rouge, USA. The periodontal examinations were performed by a calibrated dentist who was blinded on the diabetic status of the pregnant women. Periodontitis was defined as the presence of any site with a probing depth (PD) ≥ 4 mm or a clinical attachment loss (CAL) ≥ 4 mm. The severity of periodontal disease was measured in quartiles of PD and CAL. Univariable analysis and multivariable logistic regression were used to examine the relationships between periodontal disease and GDM. Results The percentage of periodontitis was 77.4% in women with GDM and 57.5% in pregnant non-GDM women, with an odds ratio (OR) and 95% confidence interval (CI) of 2.5 (1.2–5.3). After adjusting for confounding variables of maternal age, parity, race, marital status, education, family income, smoking, alcohol consumption, systemic antibiotics in pregnancy, family history of diabetes, income, dental insurance coverage and body mass index, the adjusted OR (95% CI) was 2.6 (1.1–6.1). The adjusted ORs (95% CIs) of GDM comparing the highest-to-lowest quartiles of PD and CAL were 3.8 (1.0–14.0) and 4.5 (1.2–16.9). Conclusion This study supports the hypothesis of an association between periodontal disease and GDM.

To systematically review the epidemiologic relationship between periodontitis and type 2 diabetes mellitus (T2DM). 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. 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. There is an evident bidirectional relationship between T2DM and periodontitis. Further well-designed cohort studies are needed to confirm this finding. Our results suggest that 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.

… for diabetes onset in patients with severe periodontitis. Biological mechanisms: Type 2 diabetes is … treatment regime and we conclude that individuals with type 2 diabetes benefit from …

BackgroundType 2 diabetes mellitus (T2DM) and periodontitis are chronic inflammatory diseases with a bidirectional relationship. The uncontrolled levels of glucose in T2DM patients change the pathophysiology and balance of inflammatory mediators. Matrix Metalloproteinase-2 (MMP-2) is a zinc-dependent endopeptidase that is responsible for tissue remodeling and degradation of the extracellular matrix in periodontal tissue. Therefore, the uncontrolled levels of glucose in T2DM could lead to an imbalance in MMP-2 activity in saliva, favoring the development of periodontitis.MethodsNinety-seven T2DM patients from Hospital Dr. Donato Alarcon were included in the study. Following clinical examination, the patients were classified into four groups according to the presence and degree of periodontal disease and glycemic control. Blood and whole saliva samples (WSS) were collected from each patient. Blood samples were used for Hba1c and polymorphonuclear cells count determination, while WSS were used to determine MMP-2 activity, TIMP-1 and nitrite. MMP-2 activity was determined by zymography. TIMP-1 were determined by Western blotting, and nitric oxide (NO) levels were determined by the Griess method.ResultsOf the 97 patients with T2DM, 66 had periodontitis of different severities: 18 patients had mild periodontitis, 15 had moderate and 33 had severe. Salivary MMP-2 activity, HbA1c and TIMP-1 were positively correlated with the severity of periodontitis. On the other hand, the increase in HbA1c was negatively correlated with MMP-2 activity and quantity of TIMP-1 but was positively correlated with nitrite levels.ConclusionsT2DM with glycemic uncontrol conditions, distinct clinical alterations in periodontal tissue were identified, including a decrease in the gingival redness, increased the clinical attachment loss and imbalance of MMP-2/TIMP-1, as the possible causes of disorders promoting the progression of periodontitis. Accelerated periodontitis development with poor glycemic uncontrol likely results from the altered response of host defenses and decreased activity of polymorphonuclear cells. Taken together, these findings identify MMP-2 as a promising molecular market for periodontitis.

… Periodontitis contributes to small-scale systemic inflammation. The objective of this study … the severity of periodontitis using IL-10 (Interleukin-10) level in type 2 diabetes mellitus. …

… the severity of periodontitis and the degree of periodontal … with long-term type 2 diabetes who developed several systemic … by diabetes were evaluated together in type 2 diabetic patients…

BACKGROUND The two-way relationship between periodontitis and type 2 diabetes mellitus (T2DM) is well established. Prolonged hyperglycemia contributes to increased periodontal destruction and severe periodontitis, accentuating diabetic complications. An inflammatory link exists between diabetic retinopathy (DR) and periodontitis, but the studies regarding this association and the role of lipoprotein(a) [Lp(a)] and interleukin-6 (IL-6) in these conditions are scarce in the literature. AIM To determine the correlation of periodontal inflamed surface area (PISA) with glycated Hb (HbA1c), serum IL-6 and Lp(a) in T2DM subjects with retinopathy. METHODS This cross-sectional study comprised 40 T2DM subjects with DR and 40 T2DM subjects without DR. All subjects were assessed for periodontal parameters [bleeding on probing (BOP), probing pocket depth, clinical attachment loss (CAL), oral hygiene index-simplified, plaque index (PI) and PISA], and systemic parameters [HbA1c, fasting plasma glucose and postprandial plasma glucose, fasting lipid profile, serum IL-6 and serum Lp(a)]. RESULTS The proportion of periodontitis in T2DM with and without DR was 47.5% and 27.5% respectively. Severity of periodontitis, CAL, PISA, IL-6 and Lp(a) were higher in T2DM with DR group compared to T2DM without DR group. Sig-nificant difference was observed in the mean percentage of sites with BOP between T2DM with DR (69%) and T2DM without DR (41%), but there was no significant difference in PI (P > 0.05). HbA1c was positively correlated with CAL (r = 0.351, P = 0.001), and PISA (r = 0.393, P ≤ 0.001) in study subjects. A positive correlation was found between PISA and IL-6 (r = 0.651, P < 0.0001); PISA and Lp(a) (r = 0.59, P < 0.001); CAL and IL-6 (r = 0.527, P < 0.0001) and CAL and Lp(a) (r = 0.631, P < 0.001) among study subjects. CONCLUSION Despite both groups having poor glycemic control and comparable plaque scores, the periodontal parameters were higher in DR as compared to T2DM without DR. Since a bidirectional link exists between periodontitis and DM, the presence of DR may have contributed to the severity of periodontal destruction and periodontitis may have influenced the progression of DR.

BACKGROUND AND OBJECTIVES Serum 25-hydroxyvitamin D3 (25(OH)D3 ), a newly emerged immune regulator, is considered to be involved in type 2 diabetic periodontitis (T2DCP). However, the risk factors and genes with altered expression that influence the progression and severity of T2DCP remain unknown. Accordingly, the aim of the present study was to elucidate the relationship between 25(OH)D3 deficiency and severity of T2DCP as well as the potential mechanisms. MATERIAL AND METHODS A total of 182 subjects were divided into two groups: chronic periodontitis without diabetes (P group, n = 88) and type 2 diabetes mellitus with periodontitis (DM+P group, n = 94). Patients in both groups were further classified according to age as young (Y) and elderly (E) for a total of four groups: P/Y, P/E, DM+P/Y, and DM+P/E. Periodontal status was evaluated based on the probing depth (PD) and clinical attachment loss (CAL). The serum levels of human 25(OH)D3 , interleukin (IL)-1β, and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assays. Immunohistochemistry was used to measure the expression of protein tyrosine phosphatase non-receptor type 2 (PTPN2), vitamin D receptor (VDR), and JAK/STAT proteins in the gingival tissue. RESULTS Serum 25(OH)D3 levels were lower in the DM+P group than those in the P group (P < 0.001). When the patients were subgrouped according to age, 25(OH)D3 deficiency was more commonly found in DM+P/E than in DM+P/Y (67% vs 51%), with a significant difference detected in the 25(OH)D3 quartile of 15-20 ng/mL (P = 0.007). The 25(OH)D3 level showed a significant negative correlation with fasting blood glucose (FBG) (r = -0.623), serum IL-1β (r = -0.392), serum TNF-α (r = -0.218), PD (r = -0.269), and CAL (r = -0.305) in the DM+P group (all P < 0.05), but not with hemoglobin A1c (P = 0.123). Additionally, reduced VDR and PTPN2 expression levels were observed in DM+P patients, whereas JAK1 and p-STAT5 protein levels were increased in this group. CONCLUSIONS Vitamin D3 deficiency is strongly associated with T2DCP, and age mediates this relationship. Abnormal FBG and IL-1β levels should be considered as important potential risk factors for the progression and severity of T2DCP. Moreover, 25(OH)D3 deficiency may be related to the immune function of T2DCP by weakening PTPN2 signaling.

BACKGROUND: Diabetes is a major risk factor for the development of periodontal disease in certain populations. The prevalence of type 2 diabetes is increased in Hispanic Americans, but its impact on the extent and severity of periodontal disease in this population has not been determined. METHODS: Sixty-three Hispanic Americans, aged 33 to 72 years, from South Texas were grouped based on the presence or absence of type 2 diabetes. Past medical histories, including smoking, were obtained. Periodontal status was evaluated by measuring probing depth (PD), clinical attachment level (CAL), plaque, bleeding on probing, visual gingival inflammation, and calculus. RESULTS: Type 2 diabetes was associated frequently with major medical complications in this population. Diabetes was associated with significantly more calculus formation and tooth loss and an increased extent and severity of periodontitis. Subjects with diabetes had nearly three times the mean CAL and frequency of PD >6 mm than subjects without diabetes and nearly twice the frequency of moderate to advanced attachment loss (> or =3 mm). Smoking and diabetes had significant independent effects on mean CAL and the frequency of deep pockets. Diabetes and smoking combined were associated with a significantly higher frequency of sites with CAL > or =3 mm compared to healthy non-smokers, healthy smokers, and non-smokers with diabetes. CONCLUSIONS: Hispanic Americans with type 2 diabetes had more supra- and subgingival calculus, an increased extent and severity of periodontal destruction, and an increased frequency of tooth loss due to periodontitis. An additive/synergistic contribution of type 2 diabetes and smoking for increasing the extent of periodontal disease was observed.

Background Our study attempted to observe the value of periodontal curettage combined with root planing on moderate-to-severe chronic periodontitis in patients with type 2 diabetes. Methods There involved 72 patients with type 2 diabetes mellitus complicated with moderate-to-severe chronic periodontitis who were diagnosed and treated in our hospital from January 2019 to December 2019. The patients enrolled were randomly divided into four groups using a computer-generated table: root planing and periodontal curettage combined group ( n = 18), root planning group ( n = 18), periodontal curettage group ( n = 18) and cleansing group ( n = 18). Blood glucose, plaque index (PI), gingival index (GI), probing depth (PD), attachment loss (AL), serum levels of inflammatory factors (Tumor Necrosis Factor Alpha [TNF- α] and hypersensitive C-reactive protein [hs-CRP]) were observed before and after treatment. The collecting dates were analyzed by the chi-square χ 2 test, repeated measurement analysis of variance, or t-test according to different data types and research objectives. Results Before treatment, there was no significant difference in PI, GI, PD and AL among the four groups ( P > 0.05), while after 3-month treatment, the levels of PI, GI, PD and AL in the combined group were lower than those in the root planing group, periodontal curettage group and cleansing group, with both root planing group and periodontal curettage group significantly lower than cleansing group ( P < 0.05). The fasting blood glucose, 2-h postprandial blood glucose and glycosylated hemoglobin in the combined group, root planing group, periodontal curettage group and cleansing group were significantly lower than those before treatment ( P < 0.05). Before treatment, there was no significant difference in TNF- α and hs-CRP among the four groups ( P > 0.05), but the levels of TNF- α and hs-CRP in the four groups decreased significantly after 3-month treatment ( P < 0.05). The levels of TNF- α and hs-CRP in the combined group were lower than those in the root planing group, periodontal curettage group and cleansing group, and those in the root planing group and periodontal curettage group were significantly lower than those in the cleansing group ( P < 0.05). Conclusion The combination therapy of periodontal curettage and root planing exerted beneficial effects on moderate-to-severe chronic periodontitis in patients with type 2 diabetes mellitus, which holds the potential to maintain the level of blood glucose and improve the quality of life of the patients.

OBJECTIVE To investigate the association between glycemic control of type 2 diabetes mellitus (type 2 DM) and severity of periodontal disease (PD). METHODS One hundred and twenty-six Saudi diabetic females, aged 35-70 years, attending the Diabetic Center of King Abdul-Aziz Hospital, Riyadh, Saudi Arabia were included in the study. In Group I (better control with hemoglobin A1c (HbA1c) <9%) we assigned 74 subjects and in Group II (poor control with HbA1c >9%) 52 subjects. The periodontal parameters recorded were plaque index, bleeding index, presence of calculus, pocket depth measurement, and clinical attachment level. These parameters were evaluated in a randomized half mouth examination. RESULTS Age, duration of diabetes, percentage of plaque index and bleeding index showed no significant difference between the 2 groups. In contrast, there was a significantly higher percentage of calculus, PD > or = 4 mm and loss of attachment level (3-4 mm) in the poorly controlled diabetic patients, as compared to the better-controlled group. CONCLUSION There was a significant association of the loss of attachment level (3-4 mm) with PD in poorly controlled diabetic patients, as compared to better-controlled patients. Poor-control diabetics (Group II) exhibited an increased percentage of calculus and greater risk for periodontitis.

The inflammatory response plays a central role in the pathophysiology of various chronic diseases such as periodontitis, type 2 diabetes mellitus (T2DM), and coronavirus disease 2019 (COVID-19), whose coexistence is associated with an increase in clinical complications and a more severe and serious course of these diseases. Current evidence on the interrelationship between periodontitis, T2DM, and COVID-19 remains insufficient, highlighting the need for further research to elucidate these associations. The main aim of this narrative review is to provide the current landscape of the most relevant aspects of the interrelationship between periodontitis, T2DM, and COVID-19. This narrative review was carried out through a specialized, exhaustive, and structured search of published studies indexed in the electronic databases PubMed and LILACS, for the inclusion of studies in English and Spanish, respectively, without date restriction. A search strategy was performed using the Boolean operators AND, OR, and NOT, with the following DeCS/MeSH terms: “periodontal disease”, “periodontitis”, “type 2 diabetes mellitus”, “SARS-CoV-2”, and “COVID-19”. A variety of articles were included, focusing on the most relevant aspects of the interrelationship between periodontitis, T2DM, and COVID-19. Findings suggest that inflammation is a unifying mechanism, which leads to the severity of these conditions through four shared axes: (1) a clinicopathological axis involving systemic manifestations; (2) an axis associated with metabolic alterations linked to glycemic dysregulation; (3) an axis related to enzyme overexpression linked to altered angiotensin-converting enzyme (ACE)-2 expression and glucose metabolism; and (4) an inflammatory axis. These synergistic interactions can cause these three diseases to mutually enhance each other, creating a vicious cycle, worsening the patient’s health.

INTRODUCTION The prevalence of periodontitis is significantly higher among people with poorly controlled diabetes mellitus. Majority of tissue destruction in periodontitis is considered to be the result of an aberrant inflammatory/immune response to microbial plaque and involve prolonged release of reactive oxygen species (ROS). There is increased evidence for compromised antioxidant capacity in periodontal tissues and fluids which may be an added factor for tissue damage in periodontitis. AIM To study the possible role of Reactive oxygen species (ROS) and antioxidant status in blood among chronic periodontitis patients with and without Type 2 Diabetes mellitus. MATERIALS AND METHODS The study comprised of total 100 subjects among which 25 were normal healthy controls, 25 were gingivitis patients, 25 were chronic periodontitis patients (CP) and 25 were having chronic periodontitis with type 2 diabetes (CP with DM). ROS levels were determined as MDA (Malondialdehyde) and antioxidant status as plasma total antioxidant capacity (TAC), vitamin C and erythrocyte Superoxide dismutase (SOD) and catalase activity. RESULTS There was significant increase in MDA levels in all the patient groups compared with healthy controls (p<0.05). The decrease in TAC, Vitamin C and SOD levels among CP with DM patients as compared to controls was highly significant (p<0.01). There was a positive correlation between the probing pocket depth and MDA levels among periodontitis patients with diabetes (r=0.566, p=0.003). CONCLUSION There is increased oxidative stress in chronic periodontitis with and without type 2 diabetes indicating a common factor involvement in tissue damage. More severe tissue destruction in periodontitis is associated with excessive ROS generation which is positively correlated in type 2 diabetic subjects.

… type 2 diabetes and CP and 20 systemically healthy patients with CP were enrolled in this study. The patients with diabetes … To overcome the possible impact of periodontitis severity on …

… The present study demonstrates the severity of periodontitis in patients with type 2 diabetes, with an increased PD being significantly associated with glycemic control. The reasons for …

… The incidence of severe chronic periodontitis is 5–10% of … : Type 2 diabetes with periodontitis (DP), Type 2 diabetes with no periodontitis (DNP) and non-diabetes with periodontitis (NDP…

… The aim of the present study is to evaluate associations between glycemic control status and progression of periodontitis and tooth loss among individuals during PMT. …

The mechanism by which chronic periodontitis (CP) affects type 2 diabetes (T2DM) remains unclear. Therefore, the aim of this study is to evaluate the effects of periodontal therapy (PT) on the glycemic control and adipokines of patients with T2DM and CP with the purpose of elucidating the possible mechanisms by which CP influences T2DM. Forty-four patients with T2DM and CP were randomly divided into two groups according to whether they underwent PT. Periodontal status, blood glucose, and the levels of serum tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), adiponectin (APN), and fibroblast growth factor-21 (FGF-21) were measured at baseline and after 3 months. The results revealed that the probing depth (PD) and attachment loss (AL) were significantly improved, the serum levels of TNF-α and IL-6 were significantly decreased, and APN and FGF-21 exhibited substantial increases in the intervention group after 3 months (p < 0.05), whereas no significant changes were observed in the control group. The glycated hemoglobin (HbA1c) levels in both groups decreased significantly after 3 months compared with baseline (p < 0.05), but the intervention group exhibited a significantly greater change (p < 0.05). In conclusion, PT may relieve periodontal inflammation, which causes a reduction of insulin-antagonizing adipokines and an increase in insulin-sensitizing adipokines, thereby eliciting an improvement in glycemic control.

The aim of the present study was to investigate whether non‐surgical periodontal treatment reduces glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels in diabetic patients.

… Cross-sectional analysis of different variables of patients with non-insulin dependent diabetes and their periodontal status. Int J Periodontics Restorative Dent 2004; 24(1): 71-79 …

Periodontitis and diabetes mellitus are two highly prevalent chronic conditions that share a bidirectional relationship, significantly impacting public health. Periodontitis, a gum inflammation caused by microbial dysbiosis, aggravates glycemic control in diabetics, while uncontrolled diabetes heightens periodontitis severity. These conditions create a vicious cycle, where inflammation and microbial dysbiosis mutually drive disease progression, exacerbating systemic health. The underlying mechanisms involve inflammation, immune dysfunction, and microbial dysbiosis, with both diseases contributing to a chain of chronic inflammation that exacerbates systemic health. This relationship is significant because managing one condition can significantly impact the other. In diabetic individuals, interventions such as periodontal therapy have shown effectiveness in improving glycemic control, underscoring the potential of integrated strategies for managing these conditions simultaneously. In this review, we highlight the importance of a deeper understanding of the molecular and immunological interactions between these diseases is essential for developing integrated therapeutic approaches, with the potential to enhance the quality of life of the patient significantly.

… group of patients with Diabetes Mellitus with similar periodontal status received no periodontal treatment as in the present study. Improvement of glycemic control with a reduction in …

… periodontitis (AP) and the glycemic control … status. Data reported in the present study, together with the results of previous studies, further support a relationship between glycemic control …

Aim: The aim of this observational study was to assess the periodontal and salivary status of patients with type 1 diabetes mellitus (T1DM). Materials and Methods: Thirty patients were divided into a test group (DM1G – T1DM, n = 15) and a control group (CG – normoglycemic, n = 15). Periodontal clinical parameters were evaluated using probing depth (PD), bleeding on probing (BOP), clinical attachment level (CAL), and plaque index (PI). Salivary tests assessed pH, buffering capacity, salivary glucose, and peroxidase activity. Capillary blood glucose was recorded for all patients, and glycated hemoglobin (HbA1c) was measured only for patients with T1DM. Statistical analysis was performed using Student’s t-test and Pearson’s correlation coefficient (P < 0.05). Results: The results showed significantly higher PI and BOP values in DM1G (P < 0.01). Positive correlations were found between HbA1c, PI, and BOP (P < 0.01). Capillary blood glucose levels differed between groups (P < 0.01). Positive correlations between capillary blood glucose, PD, and CAL were found only in the CG (P < 0.01). No significant differences were observed between the groups for salivary parameters (P > 0.05). Conclusions: Patients with T1DM exhibit poorer periodontal conditions compared to normoglycemic individuals, although no significant differences were found in salivary parameters between the two groups.

… The chi-square test was employed to compare xerostomia, hyposalivation, and periodontal status with glycemic control levels in patients with T2DM. Pearson’s correlation was used to …

Background Diabetes Mellitus and periodontitis are chronic diseases with known reciprocal association. Studies have shown that uncontrolled diabetes increases the risk of development and progression of periodontal disease. This study aimed to explore the association and severity of periodontal clinical parameters and oral hygiene with HbA1c levels in non-diabetics and T2DM patients. Materials and methods In this cross-sectional study, the periodontal status of 144 participants, categorized into non-diabetics, controlled T2DM, and uncontrolled T2DM and were assessed via the Community Periodontal Index (CPI), Loss of Attachment Index (LOA index), and the number of missing teeth, while oral hygiene was measured by utilizing the Oral Hygiene Index Simplified (OHI-S). SPSS was used for data analysis. Chi-square test was used to find out the association of different independent variables with HbA1c groups, while ANOVA and post-hoc tests were run for inter-group and intra-group comparison respectively. Results Out of 144 participants, the missing dentition was prevalent in uncontrolled T2DM with mean 2.64 ± 1.97 (95% CI 2.07–3.21; p = 0.01) followed by controlled T2DM 1.70 ± 1.79 (95% CI 1.18–2.23; p = 0.01) and non-diabetics 1.35 ± 1.63 (95% CI 0.88–1.82; p = 0.01) respectively. Furthermore, non-diabetics had a higher proportion of CPI score 0 (Healthy) [30 (20.8%); p = 0.001] as compared to uncontrolled T2DM [6 (4.2%); p = 0.001], while CPI score 3 was more prevalent in uncontrolled T2DM in comparison to non-diabetics. Loss of attachment (codes-2,3 and 4) was also frequently observed in uncontrolled T2DM compared to non-diabetics (p = 0.001). Similarly, based on Oral Hygiene Index- Simplified (OHI-S), the result showed that poor oral hygiene was most commonly observed in uncontrolled T2DM 29 (20.1%) followed by controlled T2DM patients 22 (15.3%) and non-diabetic [14 (9.7%); p = 0.03]. Conclusion This study showed that periodontal status and oral hygiene status were deteriorated in uncontrolled T2DM patients compared to non-diabetic participants and controlled T2DM.

… in attachment loss and … HbA1c levels and the different levels of periodontal health status. Furthermore, the objectives were to determine if periodontitis was associated with high HbA1c …

Aim: We investigate whether periodontal measures are cross-sectionally associated with prediabetes and cardiometabolic biomarkers among non-diabetic younger adults. Materials and Methods: N=1071 participants (mean age=32.2 years[SE=0.3]; 73% female) from the Oral Infections, Glucose Intolerance and Insulin Resistance Study were enrolled. Full-mouth clinical attachment loss (fm-CAL), probing depth (fm-PD), and bleeding on probing were ascertained. Interproximal CAL (i-CAL) and probing depths (i-PD) served as our primary exposures. Glucose, HbA1c, insulin, and insulin resistance (HOMA-IR) outcomes were assessed from fasting blood. Prediabetes was defined per American Diabetes Association guidelines. Prediabetes prevalence ratios (PR[95%CI]) and mean[SE] cardiometabolic biomarkers were regressed on periodontal variables via multivariable robust variance Poisson regression or multivariable linear regression. Results: Prevalence of prediabetes was 12.5%. Fully-adjusted prediabetes PR in Tertiles 3 vs 1 of mean i-CAL was 2.42(1.77,3.08). Fully-adjusted fasting glucose estimates across i-CAL tertiles were 83.29[0.43], 84.31[0.37], 86.48[0.46]; p for trend<0.01. Greater percent of sites with i-PD≥3mm showed elevated natural-log-HOMA-IR after adjustment (0–12% of sites=0.33[0.03], 13–26% of sites=0.39[0.03], ≥27% of sites=0.42[0.03]; p for trend=0.04). Conclusion: i-CAL (vs. fm-CAL) was associated with elevated fasting glucose and prediabetes whereas i-PD (vs. fm-PD) was associated with insulin resistance. Future studies are needed to examine periodontal disease and incident prediabetes.

BACKGROUND Type 2 diabetes mellitus (T2DM) has been considered by many studies to have a bidirectional relationship with periodontitis. This systematic review and network meta-analysis aimed to investigate the impact of different states of T2DM when stratified by baseline HbA1c on the clinical outcomes of non-surgical periodontal treatment (NSPT). METHODS This study followed the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines and involved an electronic literature search (from inception to the 2nd of January 2023). The study included at least two groups of patients: chronic periodontitis only (No-DM) or periodontitis and well-controlled/poorly controlled type 2 diabetes mellitus (WC/PC-T2DM). Clinical outcomes included probing depth (PD) reduction, bleeding on probing reduction, and clinical attachment level (CAL) gain. Direct and indirect comparisons between groups were assessed by network meta-analysis, thus allowing us to establish a treatment ranking. RESULTS Ten prospective cohort studies (11 data sets) were included for qualitative analysis and network meta-analysis. The data included in this study had high consistency; in addition, a funnel plot and Egger's test showed that the articles had low publication bias. Network meta-analysis showed that the effect of NSPT in the No-DM group was significantly better than the WC-T2DM group [weighted mean difference (WMD) = 0.09, 95% confidence interval (CI) (0.01, 0.18)] and the PC-T2DM group [WMD = 0.09, 95% CI (0.01, 0.18)] in terms of CAL gain and better than the PC-T2DM group [WMD = 0.15, 95% CI (0.02, 0.28)] in terms of PD reduction. According to the surface under the cumulative ranking value, the No-DM group had the highest probability of achieving the best outcome following NSPT. CONCLUSIONS Collectively, our analyses show that T2DM exerts significant effects on the outcomes of NSPT.

… aged 36–50 years recalled once a year and given symptomatic dental care, had more AL in interproximal areas during the last 2 years of follow-up, while the overall attachment loss …

… Periodontal disease was assessed by attachment loss (AL) and the number of missing teeth… whether HbA1c or WBC may act as an intermediator between diabetes and periodontal …

Background: Periodontal diseases, initiated by microbial plaque biofilm, are inflammatory conditions affecting the supporting structures of teeth. Diabetes mellitus is a significant risk factor for periodontitis, and a bidirectional relationship exists where chronic periodontal inflammation may impair glycemic control. However, the impact of periodontal treatment on glycemic outcomes remains inconclusive. This study aimed to assess the effect of non-surgical periodontal therapy on metabolic control, as measured by HbA1c levels, in patients with type 2 diabetes and mild-to-moderate generalised chronic periodontitis. Materials and Methods: A randomized controlled clinical trial was conducted at the Department of Periodontology, Manipal College of Dental Science, Manipal, Karnataka, India, with ethical clearance from the Institutional Ethics Committee (IEC No. 151/2011). One hundred eligible participants, aged 30 to 70 years, diagnosed with type 2 diabetes (HbA1c 6.5-7.5%) and mild to moderate chronic periodontitis (clinical attachment loss [CAL] 1–4 mm per AAP 1999 classification), were recruited. Participants were randomized into two groups (n = 50 each): a test group receiving non-surgical periodontal therapy (scaling and root planing) and a control group receiving no periodontal intervention. HbA1c levels were assessed at baseline and 3 months using high performance liquid chromatography. Clinical periodontal parameters (plaque index, gingival index, modified sulcus bleeding index, CAL, and probing pocket depth) were also assessed. Data were analysed using SPSS version 14, with paired t-tests for within-group comparisons and independent t-tests for intergroup differences, with P < 0.05 considered statistically significant. Results and Conclusion: The test group showed greater improvements in all periodontal parameters compared to controls, though HbA1c levels did not differ significantly over three months. Overall, the findings indicate a modest link between better periodontal health and a slight HbA1c reduction in well-controlled diabetes.

Diabetes affects one in 10 adults and periodontal disease affects four in 10 adults in the USA, and they are linked. Individuals with diabetes are more likely to suffer from periodontal disease and periodontal disease affects glycemic control and complications of diabetes. The role of diabetes as a risk factor for periodontal disease and other oral conditions will be discussed in this review. The fact that type 2 diabetes, especially uncontrolled, is a risk factor for periodontal disease has long been recognized. However, the role of type 1 diabetes and gestational diabetes in periodontal risk has recently been described. Also, diabetes as a risk factor for tooth loss has more recently been described and the deleterious effects of tooth loss, especially edentulism, in comparing the diets of patients with diabetes is now fully appreciated. From longitudinal studies it is clear that diabetes often precedes periodontitis and, hence, may contribute to the causal pathway of periodontitis. Other oral manifestations of diabetes include increased risk of oral and nonoral (vaginal) fungal infections. In patients with diabetes there is often reduced salivary flow associated with diabetes medications and neuropathy affecting the salivary glands. This may lead to increased caries. Burning mouth, resulting from diabetes neuropathy, and taste impairment may also be seen. It has long been known that there is delayed wound healing in patients with diabetes, especially if uncontrolled. Hence, it is critical to achieve good glycemic control before carrying out surgical procedures or dental implant placement in patients with diabetes.

… on the role of diabetes as a significant contributing factor for periodontal disease. … diabetes appears to be an important factor in the evaluation of diabetes as a risk factor for periodontal …

… of attributable risk for most periodontal risk factors and therefore, … risk so that priorities can be made to determine which risk … disease, the effects of diabetes on periodontal disease will be …

… of periodontal disease as determined by using either periodontal attachment loss or radiographic bone loss parameters, indicating that T2DM is a risk factor for periodontal disease.The …

… factor deterioration of diabetes mellitus. The present review … diabetes mellitus and periodontitis. The potential mechanisms involved in the deterioration of diabetic status and periodontal …

… systemic relationships between diabetes and periodontitis. More … common changes in systemic physiology have provided initial … to increased systemic inflammatory cytokine production, …

Objective The objective of this case–control study was to quantify the immune responsiveness in individuals with type 2 diabetes (T2D) as compared with patients without diabetes (NT2D) diagnosed with periodontitis. Research Design and Methods Peripheral blood was collected from 20 patients with moderate-to-severe chronic periodontitis (10 T2D, 10 NT2D). Blood samples were stimulated with ultrapure Porphyromonas gingivalis and Escherichia coli lipopolysaccharide (LPS) for 24 hours. 14 cytokines/chemokines were quantified in culture supernatants using multiplex technology. Results T2D individuals demonstrated higher unstimulated levels of interleukin 6 (IL-6), IL-1β, tumor necrosis factor α, interferon γ, IL-10, IL-8, macrophage inflammatory protein 1α (MIP1α), and 1β (MIP1β), and higher stimulated levels of IL-6, IL-8, IL-10, MIP1α and MIP1β, along with lower unstimulated and stimulated levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) when compared with NT2D (p<0.05). Importantly, the LPS-induced levels of IL-6, IL-8, IL-10 and MIP1α strongly correlated with severity of disease, measured by pocket depths (PD), within the T2D group (r2≥0.7, p<0.05), but not within NT2D. Conclusions Among patients with chronic periodontitis, patients with T2D seem to have an enhanced LPS-induced immune responsiveness than individuals without diabetes, which correlates with periodontal disease severity, concomitant with a less robust GM-CSF response. This data may in part explain the higher predisposition to periodontitis in this population.

… a significantly higher prevalence of periodontitis in diabetics than in non-diabetics, with age … As such, the systemic inflammation associated with periodontal disease could encourage …

… in periodontal … systemic antibiotics and/or surgery, to treat periodontitis may be necessary to evaluate the threshold, if any, for the effect of periodontal therapy on systemic inflammatory …

CONTEXT: Inflammatory periodontal diseases exhibit an association with multiple systemic … This article overviews the current evidence linking periodontal diseases to diabetes, …

The concept of focal infection or systemic disease arising from infection of the teeth was generally accepted until the mid‐20th century when it was dismissed because of lack of evidence. Subsequently, a largely silo approach was taken by the dental and medical professions. Over the past 20 years, however, a plethora of epidemiological, mechanistic and treatment studies have highlighted that this silo approach to oral and systemic diseases can no longer be sustained. While a number of systemic diseases have been linked to oral diseases, the weight of evidence from numerous studies conducted over this period, together with several systematic reviews and meta‐analyses, supports an association between periodontitis and cardiovascular disease, and between periodontitis and diabetes. The association has also been supported by a number of biologically plausible mechanisms, including direct infection, systemic inflammation and molecular mimicry. Treatment studies have shown that periodontal treatment may have a small, but significant, systemic effect both on endothelial function and on glycemic control. Despite this, however, there is no direct evidence that periodontal treatment affects either cardiovascular or diabetic events. Nevertheless, over the past 20 years we have learnt that the mouth is an integral part of the body and that the medical and dental professions need to work more closely together in the provision of overall health care for all patients.

… of systemic inflammation as mediators of the associations between periodontitis and IFG or diabetes. … We also tested whether the associations between periodontitis and IFG or diabetes …

BACKGROUND In Indonesia, most of diabetic patients had periodontitis and 75.3% of them had severe periodontitis. Previous study found that hyperglycemia and or local inflammation (such as periodontitis) modulated systemic pro-inflammatory and anti-inflammatory cytokines. AIMS This study aimed to investigate the effect of DM and or periodontitis on systemic cytokines and adipocytokines levels. METHODS AND MATERIALS A total of 57 participants with age of 29-71 years were recruited for this study. We divided them into three groups; DM-periodontitis (n = 22), periodontitis without DM (n = 16) and control (n = 19). All participants underwent physical examinations (BMI, WC, periodontal status examination) and laboratory examinations (FBG, fasting insulin, CRP, adiponektin, leptin, TNF-α and IL-10). RESULTS The proportion of severe periodontitis were higher in DM-periodontitis group compared to periodontitis without DM (77.3% vs 6.2%). DM-periodontitis group had lower adiponectin levels than that of periodontitis without DM group [5860.78 ± 4182.40 vs 9553.13 ± 6794.73; p = 0.046]. TNF-α/IL-10 ratio was significantly higher in the periodontitis without DM compared to control group [1.96 (1.68-2.32) vs 1.55 (1.27-1.85); p = 0.015]. CONCLUSION Local inflammation such as periodontitis, elevated systemic inflammatory markers (TNF-α/IL-10 ratio). Meanwhile chronic hyperglycemia alter adipocytokines level. The changes of systemic inflammation among diabetic group had not been shown yet in this study since some antidiabetic and antilipid drugs possess anti-inflammtory effect. Age, WC and FBG correlated with severe periodontitis. Adiponectin, leptin, TNF-α and IL-10 levels did not correlated with severe periodontitis.

Periodontitis is a chronic oral infectious inflammatory disease caused by dental plaque, affecting approximately 35% - 50% of adults globally. Far from a localized oral condition, it exerts systemic pathogenic effects through multiple biological conduits. This review synthesizes current evidence on the bidirectional associations between periodontitis and a broad spectrum of systemic disorders, including cardiovascular disease (CVD), diabetes mellitus (DM), respiratory diseases, preterm birth, Alzheimer’s disease (AD), chronic kidney disease (CKD), rheumatoid arthritis (RA), and Helicobacter pylori (H. pylori) infection. Furthermore, the review delves into the potential pathophysiological mechanisms underpinning these associations, with emphasis on bacterial translocation, systemic inflammation, immune dysregulation, and oxidative stress pathways. The concluding remarks underscore the critical importance of preserving optimal periodontal health as a cornerstone of systemic wellbeing.

Abstract For decades, periodontitis has been considered to be a local inflammatory disease of the periodontal tissues in the oral cavity. Initially, associations of periodontitis with a multitude of noncommunicable diseases were each studied separately, and relationships were shown. The associations of periodontitis with morbidities, such as cardiovascular diseases, rheumatoid arthritis, diabetes mellitus, respiratory diseases, have been demonstrated. As most such studies were cross‐sectional in nature, questions about causality cannot be univocally answered. And periodontitis as an independent risk factor for one systemic disease, becomes even more difficult to assess since recently periodontitis has also been associated with multimorbidity. Periodontitis and many systemic diseases share environmental, lifestyle and genetic risk factors, and share immunopathology. Moreover, suffering from one common noncommunicable disease may increase the susceptibility for another such chronic disease; the systemic effects of one condition may be one of various risk factors for another such disease. The overarching effect of any systemic disease is it causing a pro‐inflammatory state in the individual; this has also been shown for periodontitis. Moreover, in periodontitis a prothrombotic state and elevated immunological activity have been shown. As such, when we consider periodontal disease as another systemic disease, it can affect the susceptibility and progression of other systemic diseases, and importantly, vice versa. And with this, it is not surprising that periodontitis is associated with a variety of other noncommunicable diseases. The medical definition of a systemic disease includes diseases that affect different organs and systems. Thus, the aim of this opinion paper is to propose that periodontitis should be considered a systemic disease in its own right and that it affects the individual's systemic condition and wellbeing. The dental and medical profession and researchers alike, should adapt this paradigm shift, advancing periodontal disease out of its isolated anatomical location into the total of chronic noncommunicable diseases, being for some conditions a comorbid disease and, vice versa, comorbidities can affect initiation and progression of periodontal disease.

… systemic inflammation sustained by PD and direct systemic infectious actions by periodontal … Diabetes seems to modify periodontal tissues in several ways including immunological …

BackgroundGestational diabetes mellitus (GDM) is glucose intolerance with first onset during pregnancy and is associated with serious maternal and fetal complications. The etiology of GDM is not well understood, but systemic inflammation effects on insulin signaling and glucose metabolism is suspected. Periodontal disease is a chronic inflammatory condition that induces local and host immune responses and has been evaluated for a potential role in development of GDM. Results from studies evaluating the association between periodontitis and GDM are mixed. We performed a systematic review and meta-analysis to summarize available data regarding the association between periodontitis and GDM.MethodsTwelve electronic databases were searched for observational studies of the association between periodontitis and GDM through March 2016. Eligible studies were assessed for quality and heterogeneity. Random effects models were used to estimate summary measures of association.ResultsWe identified 44 articles from 115 potentially relevant reports of which 10 studies met our eligibility criteria. Clinical diagnostic criteria for periodontitis and GDM varied widely among studies, and moderate heterogeneity was observed. Random effects meta-analysis of all included studies with a total of 5724 participants including 624 cases, showed that periodontitis is associated with an increased risk of GDM by 66 %, (OR = 1.66, 95 % CI: 1.17 to 2.36; p < 0.05), I2 = 50.5 %. Similar results were seen in sub-analysis restricted to data from methodologically high quality case–control studies including 1176 participants including 380 cases, (OR = 1.85, 95 % CI: 1.03 to 3.32); p < 0.05), I2 = 68.4 %. Meta-analysis of studies that adjusted for potential confounders estimated more than 2-fold increased odds of GDM among women with periodontitis (aOR = 2.08, 95 % CI: 1.21 to 3.58, p = 0.009, I2 = 36.9 %).ConclusionMeta-analysis suggests that periodontitis is associated with a statistically significant increased risk for GDM compared to women without periodontitis. Robust prospective study designs and uniform definition for periodontitis and GDM definitions are urgently needed to substantiate these findings.

The effects and consequences of periodontal diseases might not be confined to the oral cavity. A great body of evidence has arisen supporting the claim demonstrating an association with several systemic conditions and diseases. With different levels of evidence, an association between periodontal disease and cardiovascular disease, diabetes, psoriasis, rheumatoid arthritis, pregnancy outcomes and respiratory diseases has been established. However, the true nature of this association, if it is causal, still remains elusive. For a better understanding of the complex relationships linking different conditions, interventional studies now begin to focus on the possible outcomes of periodontal treatment in relation to the events, symptoms and biomarkers of several systemic disorders, assessing if periodontal treatment has any impact on them, hopefully reducing their severity or prevalence. Therefore, we proceeded to review the recent literature on the subject, attempting to present a brief explanation of the systemic condition or disease, what proposed mechanisms might give biological plausibility to its association with periodontal disease, and finally and more importantly, what data are currently available pertaining to the effects periodontal treatment may have. Raising awareness and discussing the possible benefits of periodontal treatment on overall systemic health is important, in order to change the perception that periodontal diseases are only limited to the oral cavity, and ultimately providing better and comprehensive care to patients.

… 4) What is the effect of periodontal intervention on metabolic control of diabetes? After a … observed that diabetes acts as a risk factor in development of periodontitis as periodontitis is …

… The exchange of PMNs from animals with systemic inflammation to healthy ones, and vice versa, demonstrated that PMNs and tissue environment are altered during chronic …

The interrelationship between periodontitis and metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has attracted increasing attention due to the significant global rise in the prevalence of both conditions. Periodontitis, a chronic inflammatory disease, affects a substantial portion of the population and parallels the growing incidence of MASLD, which currently impacts nearly 30% of the global population. The updated nomenclature reflects a deeper understanding of the condition’s metabolic origins. This narrative review focuses on the shared pathophysiological mechanisms, particularly systemic inflammation, insulin resistance, and oxidative stress that may underlie the bidirectional relationship between these diseases. These mechanisms often act in concert to promote disease development. Unlike previous literature, this review emphasizes the hypothesis that chronic periodontal inflammation may not only mirror but also contribute to the systemic metabolic dysregulation observed in MASLD. We critically assess current evidence supporting this link by highlighting the role of inflammatory mediators in bridging oral and hepatic health, and by proposing an integrated, multidisciplinary approach to its early detection and management. The aim is to offer novel insights that can help develop better prevention strategies and more effective treatments for both diseases.

Polycystic ovary syndrome (PCOS) and periodontal disease (PDD) share common risk factors. The bidirectional interaction between PCOS and PDD has been reported, but until now, the underlying molecular mechanisms remain unclear. Endocrine disorders including hyperandrogenism (HA) and insulin resistance (IR) in PCOS disturb the oral microbial composition and increase the abundance of periodontal pathogens. Additionally, PCOS has a detrimental effect on the periodontal supportive tissues, including gingiva, periodontal ligament, and alveolar bone. Systemic low-grade inflammation status, especially obesity, persistent immune imbalance, and oxidative stress induced by PCOS exacerbate the progression of PDD. Simultaneously, PDD might increase the risk of PCOS through disturbing the gut microbiota composition and inducing low-grade inflammation and oxidative stress. In addition, genetic or epigenetic predisposition and lower socioeconomic status are the common risk factors for both diseases. In this review, we will present the latest evidence of the bidirectional association between PCOS and PDD from epidemiological, mechanistic, and interventional studies. A deep understanding on their bidirectional association will be beneficial to provide novel strategies for the treatment of PCOS and PDD.

Non communicable diseases (NCDs) affect the life of an individual in terms of mortality, morbidity and financial crises. Main NCDs are diabetes mellitus (DM), cardiovascular diseases (CVD), pulmonary diseases, osteoporosis and chronic kidney diseases (CKD). About 40% of the total deaths can be controlled by eliminating the risk factors for NCDs. Periodontitis have recently been labeled as an important potential risk factor for NCDs. CKD affect the oral health status of patients by inducing gingival hyperplasia, xerostomia, calcification of root canals and delayed eruption of teeth. Periodontitis increases systemic inflammatory burden leading to worsening of CKD which in turn has been has been found to negatively affect CKD of patients on hemodialysis therapy by altering their serum albumin and C-reactive protein levels. As hypoalbuminemia leads to increased mortality in CKD patients, it needs to be avoided by reducing systemic inflammatory burden in patients receiving HD therapy. Treating periodontal disease could be one factor that might decrease the systemic inflammatory burden and thereby improve quality of life of these patients. Sources of Data: Data from descriptive, cross sectional and longitudinal studies published between 2000 and 2012 were included. Data searches based on human studies only. Data Extraction: The key words, periodontitis, chronic kidney disease and hemodialysis, on MEDLINE, approximately 120 studies were identified. 35 of them were relevant to all three keywords. Most of them were cross sectional studies and total 7 clinical trials were identified regarding checking of serum levels after periodontal therapy with variable results. Conclusion: Patients with CKD have higher prevalence of periodontal disease while non-surgical periodontal therapy has been indicated to decrease the systemic inflammatory burden in patients with CKD specially those undergoing HD therapy.

The bidirectional relationship between gastroesophageal reflux disease (GERD) and periodontitis (PD), particularly the temporal directionality, remains unclear. A systematic review and meta-analysis were conducted to evaluate bidirectional associations between GERD and PD. Three databases (PubMed, Embase, and Cochrane Library) were systematically searched from inception to December 1, 2024. Risk estimates from individual studies were pooled using random-effects models. Five studies assessed the risk of PD in patients with GERD, while three studies evaluated the risk of GERD in patients with PD. The overall analysis suggested an increased risk of PD among patients with GERD (odds ratio [OR] = 1.27; 95% confidence interval [CI]: 1.02-1.57; p = 0.029; I2 = 96.5%). However, sensitivity analyses, limited to cohort studies (OR = 1.15; 95% CI: 0.93-1.42; P = 0.05; I2 = 96.9%) and subgroup analyses, did not support this finding. Similarly, PD patients did not exhibit a higher risk of GERD (OR = 1.19; 95% CI: 0.90-1.57; P = 0.223; I2 = 94.3%). The present study could not confirm any bidirectional associations between GERD and PD. Further high-quality longitudinal studies are required to validate these findings.

Introduction A potential association between periodontitis and endometriosis has been indicated in previous observational studies. Nevertheless, the causal link between these two disorders has not been clarified. Methods Based on publicly available genome-wide association study (GWAS) summary datasets, we conducted a bidirectional Mendelian randomization (MR) study to investigate the relationship between periodontitis and endometriosis and its subtypes. Single nucleotide polymorphisms (SNPs) strongly associated with candidate exposures at the genome-wide significance level (P < 5 × 10−8) were selected as instrumental variables (IVs). The inverse variance-weighted regression (IVW) was performed to estimate the causal effect of periodontitis on endometriosis. We further conducted two sensitivity analyses, MR-Egger and weighted median, to test the validity of our findings. The main results were replicated via data from the UK Biobank. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causality. Results The IVW method suggested that periodontitis was positively associated with endometriosis of the pelvic peritoneum (OR = 1.079, 95% CI = 1.016 to 1.146, P = 0.014). No causal association was indicated between periodontitis and other subtypes of endometriosis. In reversed analyses, no causal association between endometriosis or its subtypes and periodontitis was found. Conclusions Our study provided genetic evidence on the causal relationship between periodontitis and endometriosis of the pelvic peritoneum. More studies are necessary to explore the underlying mechanisms.

… incidence of type 1 diabetes in Caucasians than in other racial groups. The incidence of childhood type 1 diabetes in… that century the incidence and prevalence of diabetes were low and …

This review investigated the association of periodontal disease with diabetes mellitus (DM) and diabetic complications. PubMed/MEDLINE was searched including search terms "periodontal" OR "periodontitis" AND "diabetic complications" OR "diabetic retinopathy" OR "diabetic nephropathy" OR "diabetic neuropathy" OR "cardiovascular disease diabetes" OR "myocardial infarction diabetes" OR "cerebrovascular disease diabetes" OR "stroke diabetes" OR "peripheral vascular disease diabetes". Fourteen studies included in this review consistently reported an increased risk for diabetic complications including microvascular, macrovascular and death in the presence of periodontal disease. Higher risks for diabetic retinopathy (odds ratios: 2.8 - 8.7), neuropathy (3.2 - 6.6), nephropathy (1.9 - 8.5), cardiovascular complications (1.28 - 17.7) and mortality (2.3 - 8.5) were reported for people with diabetes with periodontitis compared to those with diabetes who have no periodontitis. This novel review summarizes current data providing further evidence of a link between poor oral health and DM and its complications. It has also drawn attention to major limitations of the available data linking periodontal disease and diabetic complications.

… Few of these differences can be related to differences in disease prevalence. Diabetes mellitus… This paper reviews global trends in the change in prevalence of periodontitis over the last …

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

… % had advanced forms of periodontal disease. These results … prevalence of cardiovascular disease and diabetes mellitus … prevalence of cardiovascular disease and diabetes mellitus. …

Periodontal disease is conventionally defined as an inflammatory disorder involving both soft and hard periodontal structures (1). The early phase, conventionally defined as gingivitis, is characterized by a modest and selflimiting inflammation of periodontal structures. When the local inflammation progresses, the disease evolves towards periodontitis, which has been defined by the 1999 International Workshop on Classification of Periodontal Diseases as a microbially-associated and host-mediated inflammation, resulting in loss of periodontal attachment (2). In the following 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions, it was then specified that the diagnosis of periodontitis shall be based on clinical attachment loss (CAL) by circumferential assessment of erupted dentition using standardized periodontal probes with reference to cementoenamel junction (3). According to the pathophysiological basis, periodontitis can be classified in three different forms, i.e., periodontitis, periodontitis associated with systemic diseases and necrotizing periodontitis. Periodontal disease progressively evolves when left untreated, thus causing several local complications such as the development of deep periodontal lesions, periodontal bone and tooth loss, up to masticatory failure (3). It has been recently hypothesized that some bacteria responsible for periodontitis may actively enter the Original Article

Diabetes-associated periodontitis has long been attributed to hyperglycemia, primarily through advanced glycation end products (AGEs) and RAGE-mediated oxidative stress. However, recent clinical and experimental findings show that periodontitis risk persists even under good glycemic control, suggesting additional pathological factors. This review highlights hyperinsulinemia—a hallmark of insulin resistance and early-stage type 2 diabetes—as a distinct and underappreciated contributor. In mouse models, excessive insulin signaling in insulin-responsive immune cells, such as T cells and macrophages, promotes proinflammatory polarization, while insulin receptor knockout suppresses immune activation, underscoring insulin’s direct immunomodulatory role. Hyperinsulinemia also drives adipose tissue dysfunction and lipotoxicity, amplifying systemic inflammation and elevating circulating cytokines such as interleukin-6 and tumor necrosis factor–α, which may affect periodontal tissues. Moreover, in vivo studies show that insulin excess induces endothelial activation and leukocyte recruitment via CX3CL1 and angiopoietin-2 signaling. Human clamp studies further demonstrate increased levels of inflammatory mediators under euglycemic hyperinsulinemia. Collectively, these findings support a model wherein hyperinsulinemia may contribute to periodontal inflammation and bone loss through mechanisms that are independent of blood glucose levels.

… Conversely, there was a trend toward downexpression of OPG in the diabetic periodontitis … of OPG was previously observed in periodontitis biopsies from patients with type 1 diabetes. …

Periodontal and cardiovascular disease are both major health issues. Poor oral health has long been associated with the development of systemic diseases, with the typical example being the risk of endocarditis posterior to dental procedures. Through the years, the association of periodontal disease with other non-infectious systemic diseases has been brought to attention. One of the most interesting associations is the one that exists with the development of cardiovascular disease. Many studies, including systematic reviews and meta-analyses, suggest an important association between periodontal disease and ischaemic heart disease, cerebrovascular disease, heart failure, atrial fibrillation and peripheral artery disease. Among the proposed mechanisms of this relationship, systemic inflammation appears to play a major role. Evidence suggests that periodontal inflammation triggers a systemic inflammatory state that, added to the damage mediated by antibodies that cross react between periodontal pathogens and components of the intimal wall, and the direct lesion of the intima by bacteria entering the circulation, promotes atheroma plaque development and progression. There are other studies that show a clear relationship between periodontal disease severity, elevations of inflammatory markers, and the presence of atherosclerosis. Here, we give a review of the available evidence supporting this association, and the possible mechanisms involved.

Background Recent studies have highlighted the role of low-grade systemic inflammation in linking periodontitis to cardiovascular disease (CVD) outcomes, but many aspects remain unclear. This study examines the independent and reciprocal associations of periodontitis and low-grade systemic inflammation with all-cause and CVD mortality in a large-scale cohort. Methods A total of 3047 participants from the prospective, population-based Study of Health in Pomerania (SHIP-START) were followed for a period of 13.0 ± 2.4 years. For the association between various inflammation/periodontitis measures and mortality, hazard ratios (HRs) were obtained from covariate-adjusted Cox proportional hazards models. Interactions were analysed in joint models: on the multiplicative scale, HRs were reported and on the additive scale, relative excess risks due to interaction (RERI) were calculated. Subject and variable-specific interval records were used to account for time-varying exposures and covariates. Results During the observation period, 380 (12.5%) individuals died from CVD ( n  = 125) or other causes ( n  = 255). All markers of periodontitis and inflammation showed apparent associations with all-cause mortality (HRs per SD-increase: mean PPD: 1.068 (95% confidence interval (CI): 0.988–1.155), mean CAL: 1.205 (95% CI: 1.097–1.323), missing teeth: 1.180 (95% CI: 1.065–1.307), periodontitis score: 1.394 (95% CI: 1.202–1.616), leukocytes: 1.264 (95% CI: 1.163–1.374), fibrinogen: 1.120 (95% CI: 1.030–1.218), CRP: 1.231 (95% CI: 1.109–1.366), inflammation score: 1.358 (95% CI: 1.210–1.523)). For CVD mortality, all PPD related variables showed significant associations. Interaction modelling revealed some variation with respect to mortality type and exposure combinations. On the additive scale, RERIs for periodontitis score and inflammation score implied 18.9% and 27.8% excess mortality risk for all-cause and CVD mortality, respectively. On the multiplicative scale, the HRs for interaction were marginal. Conclusions Both periodontitis and inflammation were significantly associated with all-cause mortality and CVD mortality. On the additive scale, a substantial excess risk was observed due to the interaction of periodontitis and inflammation, suggesting that the greatest treatment benefit may be achieved in patients with both periodontitis and high systemic inflammation. As periodontal therapy has been reported to also reduce systemic inflammation, the possibility of a reduction in CVD mortality risk by anti-inflammatory treatments, including periodontal interventions, seems worthy of further investigation.