REGISTRO DOI: 10.69849/revistaft/ra10202004202258
Suzana Carolina Ramos Silva
Abstract
The interplay between periodontal diseases, diabetes mellitus, and hypertension underscores the complexity of systemic health and the necessity for personalized treatment strategies. Periodontal diseases (PD) are chronic inflammatory conditions that can significantly impact overall health, particularly in patients with comorbidities like diabetes and hypertension. In this context, biomarkers, which are biological molecules indicative of pathological processes, have emerged as essential tools for monitoring inflammation and tailoring therapeutic interventions to enhance the effectiveness of periodontal treatments. Recent studies highlight the importance of personalized strategies that address both oral health and systemic implications, particularly in managing glycemic levels and reducing cardiovascular complications. By taking a holistic approach to inflammation, it becomes possible to disrupt the cyclical relationship between these conditions, thereby improving the quality of life for affected individuals. The advancements in diagnostics and biomarker technologies hold promise for revolutionizing the treatment of periodontal diseases, enabling healthcare providers to offer more effective and targeted interventions, especially for vulnerable populations like those with diabetes and hypertension. This integrated approach enriches the field of periodontology and emphasizes the critical connections between oral health and overall well-being. It reinforces the need for a multidisciplinary perspective when managing chronic conditions, suggesting that collaborative efforts among various healthcare providers can lead to more comprehensive care and better outcomes for patients. In conclusion, the ongoing research and innovation in biomarker application in periodontal care not only have the potential to enhance oral health management but also to foster improvements in systemic health, highlighting the interconnectedness of these two domains.
Keywords: Periodontal diseases; Diabetes mellitus; Hypertension; Biomarkers; Personalized treatment.
Periodontal diseases (PD) are chronic inflammatory conditions that affect the supporting tissues of the teeth, with significant implications for systemic health. The complexity in controlling PD increases in patients with diabetes mellitus (DM) and hypertension (HT), due to the interaction between these conditions. Diabetes compromises the immune response, increasing vulnerability to infections such as periodontitis and making it difficult to control inflammation, while hypertension impaired tissue perfusion, hindering healing. Both conditions accelerate the progression of PD, creating a vicious cycle that intensifies periodontal inflammation and can negatively impact glycemic control and cardiovascular health. In this context, personalized therapies based on biomarkers emerge as a promising solution for more effective and precise treatment of PD in diabetic and hypertensive patients.
Biomarkers, which are biological molecules indicative of pathological processes or therapeutic responses, such as inflammatory cytokines and acute phase proteins, play a crucial role. In patients with diabetes and hypertension, biomarkers such as interleukin-6 (IL-6), C-reactive protein (CRP), and interleukin-1 beta (IL-1β) are of particular interest, as they reflect the state of chronic inflammation and the severity of periodontal disease. The use of biomarkers in the treatment of PD enables a personalized approach, allowing interventions to be tailored according to the individual molecular profile of inflammation and treatment response.
Figure 1: Action of biomarkers.
Source: Steigmann et al. (2020).
Biomarker-based therapies may include strategies for modulating inflammation with specific anti-inflammatory agents, according to the levels of inflammatory mediators identified in the patient. For example, individuals with elevated IL-6 levels may benefit from treatments with cytokine inhibitors. Additionally, the use of antibiotics and antimicrobial therapies can be directed based on the presence of biomarkers associated with specific bacterial activity in the periodontal cavity, such as IL-1β. Continuous monitoring of these biomarkers during treatment allows for adjustments in therapy based on individual response, improving clinical outcomes.
This personalized therapeutic approach offers several advantages, such as greater efficacy in treatment and prevention of systemic complications. More precise control of periodontal inflammation not only treats periodontal disease but also improves glycemic control and reduces the impact of hypertension. Furthermore, personalized therapies minimize the indiscriminate use of medications, such as antibiotics and anti-inflammatories, avoiding unnecessary adverse effects.
Despite its potential, the application of biomarker-based therapies faces challenges, such as the standardization of tests and access to advanced technologies. However, as advancements in diagnostics and artificial intelligence become more established, it is expected that these personalized therapies will become increasingly effective, providing more efficient control of PD in patients with complex systemic conditions, such as diabetes and hypertension. This evolution may not only improve periodontal health but also the overall quality of life of these patients, with positive impacts on systemic health.
The study conducted by Geisinger et al. (2016) evaluated the effects of non-surgical periodontal treatment on serum biomarkers in patients with type 2 diabetes (T2DM) and chronic periodontitis, participants in the Diabetes and Periodontal Therapy Trial (DPTT). Inflammatory biomarkers such as high-sensitivity C-reactive protein, E-selectin, TNF-α, VCAM, IL-6, IL-8, and IL-10 were analyzed. After six months, no significant differences were observed between the treatment and control groups concerning most biomarkers. However, VCAM levels increased while E-selectin levels decreased in the treatment group. Correlations between E-selectin and diabetes-related variables, such as hemoglobin A1c (HbA1c) and fasting glucose, indicate that T2DM may be primarily responsible for systemic inflammation in these patients, leading to the conclusion that non-surgical periodontal treatment did not have a significant impact on serum biomarkers, highlighting the central role of T2DM in systemic inflammation.
The study by D’Aiuto et al. (2018) investigated the effects of periodontal treatment on glycemic control in patients with type 2 diabetes and moderate to severe periodontitis. In a randomized clinical trial with 264 patients, participants were divided into two groups: one received intensive periodontal treatment (IPT) and the other received control periodontal treatment (CPT). After 12 months, the IPT group exhibited a significant reduction in HbA1c levels compared to the CPT group, with an adjusted difference of 0.6% (p<0.0001), suggesting that intensive periodontal treatment may contribute to the effective management of type 2 diabetes. These findings indicate that regular assessment and treatment of oral health are crucial in diabetes management.
The study by Al-Rawi et al. (2020) investigated the role of MicroRNAs (miRNAs) in saliva as potential predictive biomarkers for periodontal diseases in patients with and without diabetes mellitus (DM). The research analyzed the expression of four miRNAs (miRNA-146a/b, 155, and 203) in the saliva of 24 diabetic patients and 29 healthy controls, subdivided into groups with or without periodontitis. The results revealed that the expression of these miRNAs was elevated in individuals with periodontitis and/or diabetes. In particular, miRNA-155 was identified as the most reliable predictor of periodontitis among non-diabetics, while miRNA-146a was the strongest predictor in diabetic patients. These findings suggest that miRNA-146a and miRNA-155 are effective and non-invasive biomarkers for monitoring periodontal health in diabetic and non-diabetic populations.
The study by El-Makaky and Shalaby (2019) aimed to evaluate the clinical and metabolic effects of non-surgical periodontal treatment in patients with chronic periodontitis and uncontrolled type 2 diabetes. In a randomized controlled clinical trial with 88 participants, subjects were divided into two groups: one received immediate periodontal treatment, and the other received delayed treatment. Clinical and metabolic assessments, including measures such as clinical attachment level, HbA1c, probing bleeding, visible plaque, and pocket depth, were conducted at baseline and after three months. The treatment included scaling and root planing combined with systemic antibiotics (amoxicillin and metronidazole). After three months, the group that received immediate treatment showed significantly better clinical and metabolic improvements compared to the control group. The study concluded that non-surgical periodontal therapy, along with antibiotic treatment, led to significant improvements in both metabolic control and periodontal health in diabetic patients with chronic periodontitis.
Finally, the study by Wang et al. (2020) investigated the impact of periodontal therapy on cardiac function in patients with type 2 diabetes and periodontitis, recognizing that periodontitis significantly increases the risk of diabetic complications. In this clinical trial, 58 subjects were randomly assigned to a Treatment Group, which received non-surgical periodontal therapy, or a Control Group, which only received oral hygiene instructions with delayed periodontal treatment over a six-month period. Left ventricular (LV) diastolic function was assessed through echocardiography using the tissue Doppler index (E/e’ ratio), and LV hypertrophy was analyzed through the left ventricular mass index (LVMI). The results indicated that the Treatment Group showed a significant reduction in the E/e’ ratio of 1.66, along with notable improvements in periodontal conditions. Although the LVMI remained unchanged at the six-month follow-up, numerical decreases were observed in serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein, and interleukin-6, although these did not reach statistical significance. The study concluded that non-surgical periodontal therapy may improve diastolic cardiac function in patients with T2DM suffering from periodontitis.
The research by Korte and Kinney (2016) also contributed to the understanding of salivary biomarkers, evaluating panels of combinatorial markers and periodontal pathogens that demonstrate high sensitivity and specificity. Periodontal diseases require a complex inflammatory response to bacterial pathogens in susceptible hosts, leading to tissue destruction. Traditional clinical assessments often diagnose periodontitis only after the biological onset of the disease process, failing to confirm disease activity or predict future risks. Emerging technologies now allow for the measurement of combinations of inflammatory cytokines and proteinases.
The interaction between periodontal diseases, diabetes mellitus, and hypertension illustrates the complexity of systemic health and the importance of personalized approaches in treatment. Biomarkers emerge as valuable tools for monitoring inflammation and adapting therapeutic interventions, enhancing the effectiveness of periodontal treatment. Recent studies reinforce the relevance of personalized strategies that not only aim to improve oral health but also contribute to glycemic control and the reduction of cardiovascular complications. By addressing inflammation holistically, it is possible to break the vicious cycle among these conditions, improving patients’ quality of life. The ongoing advancements in diagnostics and biomarker technologies promise to transform the treatment of periodontal diseases, allowing for more effective and specific interventions for vulnerable populations, such as those with diabetes and hypertension. This integrated approach not only enriches the field of periodontology but also highlights the interconnection between oral health and overall health, underscoring the need for a multidisciplinary perspective in managing chronic conditions.
References
Al-Rawi, N., Al-Marzooq, F., Al-Nuaimi, A., Hachim, M., & Hamoudi, R. (2020). Salivary microRNA 155, 146a/b and 203: A pilot study for potentially non-invasive diagnostic biomarkers of periodontitis and diabetes mellitus. PLoS ONE, 15. https://doi.org/10.1371/journal.pone.0237004.
D’Aiuto, F., Gkranias, N., Bhowruth, D., Khan, T., Orlandi, M., Suvan, J., Masi, S., Tsakos, G., Hurel, S., Hingorani, A., Donos, N., & Deanfield, J. (2018). Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, randomised trial.. The lancet. Diabetes & endocrinology, 6 12, 954-965 . https://doi.org/10.1016/S2213-8587(18)30038-X.
El-Makaky, Y., & Shalaby, H. (2019). The Effects of Non -Surgical Periodontal Therapy on Glycemic Control in Diabetic Patients (Randomized Controlled Trial).. Oral diseases. https://doi.org/10.1111/odi.13256.
Geisinger, M., Michalowicz, B., Hou, W., Schoenfeld, E., Gelato, M., Engebretson, S., Reddy, M., & Hyman, L. (2016). Systemic Inflammatory Biomarkers and Their Association With Periodontal and Diabetes-Related Factors in the Diabetes and Periodontal Therapy Trial, A Randomized Controlled Trial.. Journal of periodontology, 87 8, 900-13 . https://doi.org/10.1902/jop.2016.150727.
Korte, D., & Kinney, J. (2016). Personalized medicine: an update of salivary biomarkers for periodontal diseases.. Periodontology 2000, 70 1, 26-37 . https://doi.org/10.1111/prd.12103.
Steigmann, L., Maekawa, S., Sima, C., Travan, S., Wang, C. W., & Giannobile, W. V. (2020). Biosensor and Lab-on-a-chip Biomarker-identifying Technologies for Oral and Periodontal Diseases. Frontiers in pharmacology, 11, 588480.
Wang, Y., Liu, H., Zhen, Z., Pelekos, G., Wu, M., Chen, Y., Tonetti, M., Tse, H., Yiu, K., & Jin, L. (2020). A randomized controlled trial of the effects of non-surgical periodontal therapy on cardiac function assessed by echocardiography in type 2 diabetic patients.. Journal of clinical periodontology. https://doi.org/10.1111/jcpe.13291.