Inflammatory Mediators in the Oral Fluids and Blood Samples of Type 1 Diabetic Patients, According to Periodontal Status—A Systematic Review
Abstract
1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Extraction of Sample Data
4.2. Study Quality and Risk of Bias
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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1. | 2. | 3. | 4. | 5. | 6. | 7. | 8. | |
---|---|---|---|---|---|---|---|---|
Sereti et al., 2020 [30]. | Y | Y | Y | Y | N | N | Y | Y |
Linhartova et al., 2018 [24]. | Y | Y | Y | Y | N | N | Y | Y |
Steigmann L. et al., 2022 [1]. | Y | Y | Y | Y | Y | Y | Y | Y |
Antonoglou et al., 2013 [31]. | Y | Y | Y | Y | Y | Y | Y | Y |
Popławska-Kita A. et al., 2014 [32]. | Y | Y | Y | Y | Y | Y | Y | Y |
Duque et al., 2017 [33]. | Y | Y | Y | Y | N | N | Y | Y |
Maksymenko et al., 2021 [34]. | Y | Y | N | Y | Y | Y | Y | Y |
Keles et al., 2020 [35]. | Y | Y | Y | Y | Y | Y | Y | Y |
1. | 2. | 3. | 4. | 5. | 6. | 7 | 8. | 9. | 10. | 11. | |
---|---|---|---|---|---|---|---|---|---|---|---|
Shinjo et al., 2019 [36]. | N | N | Y | Y | Y | Y | Y | Y | Y | Y | Y |
Lappin et al., 2015 [37]. | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
Author | Study Design | Study Aim | Inclusion Criteria | Exclusion Criteria | Sample Size | Age Group | Study Duration | Outcomes Measured | Results |
---|---|---|---|---|---|---|---|---|---|
Sereti et al., 2020 [30]. | Cross-sectional study | To compare the levels of GCF, IL-8, matrix metalloproteinase 8 (MMP-8) and AGEs in a cohort of T1DM subjects and healthy controls. | Subjects were aged between 18 and 85 years old, presented at least 10 natural teeth and were diagnosed with T1DM for more than 1 year. | (NR) | Fifty subjects with a diagnosis of T1DM were recruited from the patient cohort. Subjects aged between 18 and 85 years old, presented at least 10 natural teeth and were diagnosed with T1DM for more than 1 year. Control group of 50 systemically healthy subjects matched for age, sex and smoking status. | 18–65 years | Transversal study | GCF, IL-8, MMP-8 and AGEs, and periodontal parameters PI, GI, PD, BOP, REC, furcation and tooth mobility. | The GCF levels of IL-8, MMP-8 and AGEs did not differ significantly between the groups. Further analysis of the GCF markers in younger (<40 years) and older (≥40 years) cohorts revealed no significant differences between younger diabetics and controls or between older diabetics and controls. |
Steigmann L. et al., 2022 [1]. | Cross-sectional study | To identify salivary biomarkers that are associated with PD and measures of diabetic autonomic dysfunction. | Age-matched healthy non-obese controls with normal glucose tolerance, normal blood pressure and cholesterol. | Presence of any retinopathy, nephropathy, peripheral and autonomic neuropathy, and cardiovascular disease. | H 10 DM 10 DMN 12 | (40 ± 12, 44 ± 16 and 56 ± 11 years old in H, DM and DMN, respectively) | (NR) | IgA | The mean salivary IgA level inT1 DM was 9211.5 ± 4776.4 pg/mL, which was significantly lower than HC (17,182.2 ± 8899.3 pg/mL). IgA in DPN patients with a healthy periodontium was significantly lower (5905.5 ± 3124.8 pg/mL) compared to HC, although IgA levels in DPN patients with gingivitis (16,894.6 ± 7084.3) were not. IgA and periodontal condition were the indicators of the binary response given by HC versus T1DM, and HC versus DPN, respectively. |
Antonoglou et al., 2013 [31]. | Cross-sectional study | To explore in a cross-sectional study design whether any association exists between the extent of periodontal tissue destruction and circulating levels of sRANKL and OPG. | T1DM adult patients. | Previous antibiotic treatment (4 months). Immunosuppression patients who need antibiotic prophylactic. | 80 patients with T1DM and 56 nonsmokers. The duration of insulin therapy was 20.0 years (range 1.2– 48.0 years, median 18.3 years). | 38.6 ± 12.3 years | NR | CAL, bleeding and PD 4 mm or mean pocket depth were not significantly related to the serum levels of sRANKL and OPG and the sRANKL/OPG ratio. | A potential confident association between serum OPG and periodontal attachment loss/severity of periodontal disease in subjects with T1DM was confirmed. |
Shinjo et al., 2019 [33]. | Cohort study | To explore a subset of the Medalist cohort, who have been shown to have protection from other diabetic complications, to assess whether they are also protected from the development of periodontitis, a known complication of diabetes. | Joslin Medalist group with more than 50 years of diagnosed T1DM. | NR | 170 patients from a 50-year Medalist study were examined between 2008 and 2010. | Mean age of 64.6 ± 6.9, age at diagnosis of 11.0 ± 6.5 years and duration of T1DM of 53.4 ± 4.3 years. | From 2008 to 2015 or death. | PI GI (REC) PD CAL BOP IG P. gingivalis | Detectable serum C-peptide was associated with higher PPD and CAL. Serum IL-6 levels and Ig titers against P. gingivalis found a positive association. |
Lappin et al., 2015 [34]. | Cross-sectional study | To compare the circulating levels of IL-6, IL-8 and CXCL5 in patients with T1DM, with and without periodontitis, to control groups consisting of systemically healthy, non-smoking individuals with and without periodontitis. | Minimum two sites with PPD and CAL > 5 mm and without periodontitis treatment. | No history of smoking within past 5 years. Pregnancy. Immunosuppression. Taking antibiotics or anti-inflammatory medication for 6 weeks. Less than 20 teeth. | 104 participants in the study; 19 healthy volunteers, 23 patients with periodontitis, 28 patients with T1DM and 34 patients with T1DM and periodontitis. | Aged 20–56 (mean 36.4 ± 9.9) | 2007–2010 | AGE end product production. | Patients with diabetes and periodontitis had higher plasma levels of IL-8 than patients with periodontitis alone. Plasma levels of IL-8 correlated significantly with IFCC units, clinical probing depth and attachment loss. AGE and LPS, alone or in combination, stimulated IL-6, IL-8 and CXCL5 expression in both OKF6/TERT-2 cells and THP-1 monocytes. |
Linhartova et al., 2018 [24]. | Cross-sectional study | To determine IL-8 in plasma, CXC R2 polymorphisms and the presence of T1DM selective bacteria. | Willingness to participate, and compliance criteria of T1DM and CP, without periodontal treatment. | Coronary artery diseases, malignancies, immunodeficiency disorders, pregnancy or lactation, immunosuppression drugs, <20 teeth and the inability to consent. | 153 patients (73 healthy, 80 diabetics) | The mean ages and BMI were similar for patients with T1DM + CP and HC, but there were significant differences in mean ages between groups of HC + CP/T2DM + CP and non-periodontitis HC (mean standard deviation, SD: 59.5 ± 9.3/66.8 ± 8.5 vs. 45.5 ± 9.6, p < 0.01). | NR | Sample collection and plasma level analysis (IL-8). Genetic analysis: genomic DNA. Periodontal bacteria analysis: red complex. | Mean BMI was significantly higher in T2DM + CP patients than in non-periodontitis HC and T1DM + CP patients (mean ± SD) (29.9 ± 7.7 vs. 23.8 ± 4.2/25.1 ± 3.1, p < 0.05). Smoking status did not differ between T2DM+CP and non-periodontitis HC (5.3% vs. 7.1% smokers) or between T1DM + CP patients and HC + CP individuals (19.4% vs. 25.0% smokers). DR was present only in patients with T1DM + CP, and DPN was also present significantly more frequently in this group of patients (p < 0.01). Diabetic patients with CP had significantly higher IL-8 than HC + CP (11.02 pg/mL (6.47–15.17), p < 0.05. IL-8 and CXC R2 had no association. |
Popławska-Kita et al., 2014 [32]. | Cross-sectional study | They assessed oral hygiene and periodontal status in healthy individuals and patients with T1DM in relation to (i) their glycemic control, (ii) smoking and (iii) serum inflammatory biomarkers. | All patients and controls gave their informed consent to participate in the study and the protocol was approved by the local ethics committee. | Presence of systemic diseases other than type 1 diabetes that could influence the progression of PD, along with the intake of immunosuppressive drugs, steroids or non-steroidal anti-inflammatory drugs, pregnancy and fixed orthodontic appliances. | 107 patients for T1DM | T1DM good metabolic control HbA1c < 6.5% (34.8 ± 10.9). T1DM poor metabolic control HbA1c > 6.5% (37.9 ± 3.7.) Control group (32.3 ± 1.0). | NR. | Age, weight, systolic and diastolic pressure, Hb A1c, fasting glucose, total cholesterol, HDL, LDL, triglycerides, CRP, IL-1, TNF-α, number of teeth, OHI, CPI. | In the patients with T1DM, OHI correlated with blood pressure and serum TNF-α level, and negatively with number of teeth. |
Duque et al., 2017 [33]. | Cross-sectional study | To compare the prevalence of periodontal pathogens, systemic inflammatory mediators and lipid profiles in T1DM children with NDM children, both with gingivitis. | Children recruited from the Pediatric Dentistry Clinic. | Patients undergoing antibiotic prophylaxis for dental treatment, uncontrolled systemic diseases, immunological compromise, subjects who were wearing orthodontic devices, subjects who had been undergoing periodontal treatment 12 months before the beginning of the study, those who had been taking antibiotics within 6 months prior to the clinical examination, those with extensive caries lesions, individuals who were using an antiseptic solution in the past 3 month period and smokers. | 27 DM children and 24 NDM children | 7–13 years | NR | PPD GI PI Il-1β TNF-α IL-6 | There were no statistically significant differences in the periodontal indices of patients with DM and NDM, indicating similar periodontal status. In both groups, similar levels of TNF-α, IL-6 and Il-1β in GCF were found. |
Maksymenko et al., 2021 [34]. | Cross-sectional study | To study the levels of proinflammatory IL-18 in the oral fluid of T1DM children, and to determine their periodontal status and the level of oral hygiene. | Children with or without T1DM | Children receiving or who had previously received orthodontic treatment; smokers; periodontal or antibiotic medication during the previous six months; any other systemic disorders other than diabetes mellitus; and eruptive gingivitis. Children with diabetes mellitus who had any problems other than periodontal inflammation were also not included in our study. | 82 children: 56 children with T1DM and 26 NDM. Group 1–13 contained children with clinically healthy periodontium and no concomitant diseases; Group 2–13 contained children without concomitant diseases, but with chronic catarrhal gingivitis; Group 3–26 contained children with T1DM and healthy gums; and Group 4–30 contained children with T1DM and chronic catarrhal gingivitis. | 6–12 years old | NR | OHI GI BOP IL-18 | Children with chronic gingivitis and T1DM showed the highest level of IL-18 in oral fluid (70.91 ± 7.48 pg/mL). Increased values of IL-18 in oral fluid were associated with the presence of T1DM in children. |
Keles et al., 2020 [35]. | Cross-sectional study | To evaluate the levels of IL-18 and TNF-α in the GCF of T1DM children with gingivitis. | Children aged between 8 and 14 years; diagnosed with T1DM with an HbA1c level < 7.5% at least 12 months prior to the study, by a pedi- atric endocrinologist; exhibiting their first molars and maxillary and mandibular incisors that are fully erupted, free of cavities; and those not having any systemic disorders (for the healthy group). | Children with any other identified systemic chronic diseases; with an HbA1c level greater than 7.5%; requiring restorative and endodontic therapy; taking immunosuppressive medications within the last six months; taking any medication on a regular basis; using orthodontic appliances; having clinical attachment loss; and having any destructive periodontal disease or periodontal therapy involving antimicrobial or anti-inflammatory drugs. | 88 C=children: 44 T1DM, 44 systemically healthy. (1) Systemically and periodontally healthy children (H, n = 22), (2) systemically healthy children with gingivitis (G) (n = 22), (3) periodontally healthy children with T1DM (T1DM + H, n = 22) and (4) children with T1DM and gingi- vitis (T1DM + G, n = 22). | 8–12 years old | April–June 2019 | PI GI PPD GCF TNF-α | Diabetic children exhibited similar amounts of TNF-α and GCF IL-18 in comparison with systemically healthy children (p > 0.05). Total GI, PI, PPD, GCF volume and TNF-α levels were substantially higher in the gingival subgroups than in the H subgroups (p < 0.0001). Compared to the periodontally healthy subgroups, the gingivitis subgroups had noticeably lower IL-18 concentrations. A strong relationship between gingival inflammation and TNF-α was confirmed by the presence of high levels of TNF-α in the GCF in children with gingivitis. |
P | Population | Type 1 Diabetic Patients |
---|---|---|
I | intervention/exposure | To evaluate in both gingival crevicular fluid (GCF) and saliva samples the quantification of IL-1β, IL-6, IL-23, IFNγ, IL-1RA and IP-10, as well as IL-10, IL-17, IL-33 and RANK-L, given their described role in the inflammatory dysregulation observed in diabetic patients. |
C | comparison | Patients without periodontal disease; systemic healthy patients without type 1 diabetes mellitus disease. |
O | outcome | To analyze the inflammatory biomarkers between type 1 diabetes mellitus and periodontal disease patients. |
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Parra Meder, Á.; Costa, R.; López-Jarana, P.; Ríos-Carrasco, B.; Relvas, M.; Salazar, F. Inflammatory Mediators in the Oral Fluids and Blood Samples of Type 1 Diabetic Patients, According to Periodontal Status—A Systematic Review. Int. J. Mol. Sci. 2025, 26, 2552. https://doi.org/10.3390/ijms26062552
Parra Meder Á, Costa R, López-Jarana P, Ríos-Carrasco B, Relvas M, Salazar F. Inflammatory Mediators in the Oral Fluids and Blood Samples of Type 1 Diabetic Patients, According to Periodontal Status—A Systematic Review. International Journal of Molecular Sciences. 2025; 26(6):2552. https://doi.org/10.3390/ijms26062552
Chicago/Turabian StyleParra Meder, Álvaro, Rosana Costa, Paula López-Jarana, Blanca Ríos-Carrasco, Marta Relvas, and Filomena Salazar. 2025. "Inflammatory Mediators in the Oral Fluids and Blood Samples of Type 1 Diabetic Patients, According to Periodontal Status—A Systematic Review" International Journal of Molecular Sciences 26, no. 6: 2552. https://doi.org/10.3390/ijms26062552
APA StyleParra Meder, Á., Costa, R., López-Jarana, P., Ríos-Carrasco, B., Relvas, M., & Salazar, F. (2025). Inflammatory Mediators in the Oral Fluids and Blood Samples of Type 1 Diabetic Patients, According to Periodontal Status—A Systematic Review. International Journal of Molecular Sciences, 26(6), 2552. https://doi.org/10.3390/ijms26062552