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Effect of hyperbaric oxygen therapy on diabetes-related oral complications

Effect of hyperbaric oxygen therapy on diabetes-related oral complications

HYPERBARIC OXYGEN THERAPY IN DIABETES MELLITUS

ABSTRACT

Background: Diabetes Mellitus is a chronic disease characterized by uncontrolled blood sugar levels, which lead to end-organ damage. While the diagnosis and treatment of its complications have been extensively studied, the effect of Hyperbaric Oxygen Therapy (HBO2) on diabetes- related oral complications remains unexplored.

Aim: This prospective clinical study aims to investigate the effect of HBO2 on diabetes-related oral complications.

Methods: Twenty patients diagnosed with diabetic foot ulcers and scheduled for HBO2 were included in this study. We recorded stimulated and unstimulated saliva pH, buffering capacity, flow rate, and subjective symptoms such as dry mouth, halitosis, taste loss, difficulty swallowing, and clinical examination findings before HBO2 and after the 21st session.

Results: Upon comparing the findings, we observed a significant decrease in dry mouth and halitosis, periodontal disease severity, and healing of candida-related stomatitis and angular cheilitis. Despite not reaching statistical significance for other saliva parameters, the unstimulated salivary flow rate increased to normal limits (0.3-0.4 ml/min) in 6 out of 8 patients with a flow rate of less than 0.25 ml/min.

Conclusion: Our study investigated the effect of HBO2 on diabetes-related oral complications for the first time, highlighting symptomatic relief for dry mouth and halitosis. Although our results are insufficient to report a definitive benefit, they underscore the need for further research on the oral health effects of HBO2.

Keywords: dentistry; diabetic foot; dry mouth; halitosis; hyperbaric oxygen
Key points: Our study investigated the effect of HBO2 on diabetes-related oral complications for the first time, highlighting symptomatic relief for dry mouth and halitosis. Although our results are insufficient to report a definitive benefit, they underscore the need for further research on the oral health effects of HBO2.

INTRODUCTİON

In dentistry, hyperbaric oxygen therapy (HBO2) is known for its effectiveness in treating head and neck radiotherapy complications. After radiation therapy, several studies have demonstrated favorable effects of HBO2 on conditions such as osteomyelitis, osteoradionecrosis, and salivary gland function (1,2). Due to its proven ability to improve various biochemical mechanisms and inflammatory or immunological responses, international health authorities commonly recommend administering hyperbaric oxygen treatment for accepted indications, including air embolism, decompression sickness, carbon monoxide intoxication, necrotizing fasciitis, chronic osteomyelitis, avascular necrosis, and chronic wounds, such as diabetic or nondiabetic wounds (3).

Diabetes Mellitus is a chronic disease characterized by uncontrolled blood sugar levels, which can lead to end-organ damage. The disease diagnosis is typically based on elevated blood sugar levels and HbA1c levels, retrospectively reflecting three-month blood sugar regulation. Diabetes mellitus is associated with many complications, mainly affecting the cardiovascular system, nervous system, kidneys, eyes, and leading to various chronic wounds, particularly on the feet. Diabetic foot, a condition presenting a wide range of ulcers, often fails to improve promptly and may progress to limb amputation. Medical and surgical therapies have been widely used to treat diabetic foot, and some health authorities in different countries recommend hyperbaric oxygen treatment to accelerate wound healing and reduce amputations of the affected limb (3).

Patients with diabetes-related complications, such as diabetic foot, may also experience negative effects of diabetes on oral health, including hyposalivation and xerostomia, halitosis, dry and/or burning mouth, an increased incidence of bacterial, viral, and fungal infections, such as Candida albicans, delayed wound healing, and an increased incidence and severity of periodontal diseases and caries. Saliva plays a vital role in oral health, protecting intraoral structures against injuries caused by various pathogenic microbes and mechanical or chemical irritants. Saliva functions include defensive/buffering capacity, remineralization of teeth, restoration of soft tissues, lubrication capacity, digestion, and antimicrobial capacity. Small changes in salivary flow rate and pH can significantly impact these functions. The normal unstimulated saliva flow rate is approximately 0.3-0.4 ml/min (6). A decrease in salivary flow

rate in diabetic patients has been associated with alterations in the basement membranes of salivary glands. Although the etiology of all diabetes-related oral complications remains unclear, these complications may also be influenced by factors other than saliva, such as polyuria, microvascular changes, and neuropathies (7).

This study aims to address the following question: "Does HBO2, which has shown success in treating other diabetes-related complications, have a role in the treatment of oral complications?" The objective of this study is to investigate the effect of HBO2 on diabetes- related oral complications. As the first clinical study on this subject, we believe that it will inspire future research on the use of HBO2 in dentistry.

MATERIALS AND METHODS

The study was conducted in accordance with the ethical principles of good clinical practice and the Declaration of Helsinki. The protocol received approval from the Clinical Research Ethics Committee of Marmara University, Faculty of Dentistry, Istanbul (No.2020-453 of 20/November/2020). Participants were informed about the research requirements, and the study details were thoroughly explained to the recruited patients. Written consent was obtained from all participants before the start of the study. The study group comprised twenty patients who underwent hyperbaric oxygen therapy for nonhealing wounds related to diabetic foot ulcers. Participants received treatment at the Department of Underwater and Hyperbaric Medicine outpatient clinic, Kartal Dr. Lutfi Kirdar State Hospital, University of Health Sciences. Patients' health records were obtained, including the most recent HbA1c values, medication list, past medical and surgical history, and dental history. Patients who had received head and neck radiotherapy, had known salivary gland pathology, or had a systemic disease such as amyloidosis or Sjogren's syndrome that directly affected saliva production were excluded from the study. Patients using antidepressants, anticonvulsants, and antipsychotics were also excluded to eliminate the possibility of medication-related xerostomia.

Hyperbaric oxygen treatment was administered in a multiplace chamber at 2.4 ATA (Atmosphere absolute, 1 ATA: 760 mmHg), 120 minutes per session, five times weekly. Patients received 100% oxygen through a mask or hood. Each session consisted of three 30- minute oxygen periods with 5-minute air breaks. The study protocol involved 21 sessions completed by each participant before the final measurement of saliva.

Before the first HBO2 session, the patients' dental history, including oral hygiene habits and frequency of visits to the dentist, was recorded. Stimulated and unstimulated saliva samples were evaluated for volume (ml), pH, and buffering capacity. Additionally, oral examinations were performed, and questions were asked to assess the subjective symptoms of diabetes- related oral complications before and after 21 sessions of HBO2.

Saliva samples were collected while patients were seated in a relaxed state. Saliva flow rates were calculated by dividing the saliva sample volume (ml) by the collection time (min). To measure the stimulated salivary flow rate, patients chewed on a paraffin tablet, and the sample was collected after the first stimulated saliva was swallowed.

The pH of stimulated and unstimulated saliva samples was measured using an electronic pH meter. The buffering capacity of saliva (by Ericsson method 1959) was measured by adding 0.5 ml of saliva to 1.5 ml of 0.005 mol/l HCl. The mixture was shaken, and the final pH was measured using an electronic pH meter 20 minutes later (8).

Subjective complaints, such as dry mouth, taste loss, difficulty swallowing, and halitosis, were evaluated before and after HBO2. Subjective mouth discomfort and symptoms of xerostomia were assessed with a 10-point visual analog scale (VAS), as previously used in studies about radiotherapy complications or health problems related to COVID-19 infection (9,10).

A dentist performed intraoral examinations to evaluate oral complications related to diabetes. Findings, such as oral candidiasis (stomatitis) and periodontal problems, recorded during the examination were checked at the end of the treatment protocol.

Statistical Analysis:
The IBM SPSS Statistics 22 program was used for statistical analysis of the study findings. The normal distribution of parameters was assessed using the Shapiro-Wilks test. Descriptive statistical methods were used to evaluate the study data, including mean, standard deviation, and frequency. The paired-sample t-test was used to compare parameters with a normal distribution before and after treatment. In contrast, the Wilcoxon sign test was used for

parameters that did not show a normal distribution. Statistical significance was evaluated at the p<0.05 level.

RESULTS

The study included 20 cases, with nine (45%) female and 11 (55%) male participants aged between 45 and 76 years. The mean age was 59.45±8.99 years. HbA1c levels varied between 6.5 and 11.6, with a mean of 7.91±1.36. When asked about the frequency of tooth brushing, it was found that the average was less than once per day. Almost all the patients reported that they only visited the dentist when they had a complaint (90%). When saliva parameters were compared before and after hyperbaric oxygen therapy, no difference was observed in terms of pH and buffering capacity before and after therapy. Although the results were not statistically significant, an increase was observed in the flow rate of stimulated and unstimulated saliva (Table 1). Furthermore, the unstimulated salivary flow rate increased to normal limits (0.3-0.4 ml/min) in six out of eight patients with a flow rate of less than 0.25 ml/min.

When evaluating the subjective complaints of the patients, a statistically significant decrease was observed in dry mouth and halitosis scores after hyperbaric oxygen therapy compared to before treatment (p: 0.002; p<0.05) (p: 0.007; p<0.05) (Table 2).
Regarding clinical examination of the patients in terms of diabetes-related oral complications, the most common problems were periodontal disease and missing teeth. Warning signs of periodontal disease, such as red or swollen gums, bleeding gums, halitosis, painful chewing, and gums that have pulled away from their teeth, were observed in approximately 55% of patients. It was noticed that the severity of halitosis and gingival edema partially decreased with HBO2, but the symptoms did not completely disappear.

Stomatitis was encountered within the borders of the prosthesis in 2 out of 7 patients with removable dentures, and angular cheilitis was recorded in one patient. These candida- related findings improved after the administration of hyperbaric oxygen treatment.

DISCUSSION

Diabetes mellitus is a problematic disease that can result in severe complications, including coronary artery disease, peripheral vascular disease, peripheral neuropathy, and renal disease

(11). Complications related to the oral cavity can also occur due to high blood glucose levels and advanced glycation end-products found in the periodontium of diabetic individuals. The elevated glucose level triggers an increase in the expression of inflammatory cytokines, promoting periodontal disease (12). To ensure the reliability of salivary parameters when evaluating oral complications in diabetic patients, our study excluded patients using drugs other than antidiabetics known to affect salivary gland function and induce xerostomia, as reported by Wolff et al. in their evaluation of 269 studies (13).

Poor diabetic control often results from insufficient care, insufficient measures, and unawareness, leading to serious health problems, including inadequate foot and oral care. Previous studies have shown poor oral self-care and use of dental services among patients with diabetes (14-18). Our study also observed that diabetic patients with insufficient glycemic control and diabetic foot ulcers lacked routine oral care and dental visits.

Hyperbaric oxygen therapy has been studied for its effect on head and neck radiotherapy complications, and it has shown success in improving symptoms such as dry mouth and increasing salivary flow rate (19). In our study, which focused on diabetes-related oral complications, we obtained similar results regarding subjective symptoms. Our study is the first to investigate the effect of hyperbaric oxygen therapy on diabetes-related oral complications.

While the treatment did not significantly affect salivary flow rate, pH, and buffering capacity, it is worth noting that an improvement was observed in 6 out of 8 patients with below- normal salivary flow rates. Even minimal increases in salivary flow rate for all patients can lead to significant differences in functions such as lubrication and antimicrobial activity. Additionally, the success of hyperbaric oxygen therapy was more evident in subjective complaints, with a statistically significant decrease in the feeling of dry mouth and halitosis after treatment (p: 0.002*, 0.007*).

The relationship between salivary flow rate and subjective symptoms of dry mouth is not always straightforward, as previous studies have shown that saliva flow rate does not always correlate with subjective symptoms (21). Further studies on this subject should also evaluate salivary viscosity and glucose levels.

It is essential to recognize that hyperbaric oxygen therapy is not a standalone solution for periodontal diseases, as it would not be realistic to expect complete recovery without initial periodontal treatment, such as the mechanical removal of calculus and plaque (22,23). However, the antimicrobial effect and contribution to enhanced wound healing through improved tissue oxygenation make hyperbaric oxygen therapy a favorable treatment supporting the periodontal healing process (24-26). A multidisciplinary approach is crucial in addressing the complex problem of the negative impact of periodontitis on glycemic control (27,28).

Our study's complete recovery of oral candidiasis (stomatitis and angular cheilitis) after hyperbaric oxygen therapy suggests a potential benefit, but larger clinical studies are needed to produce scientific evidence. In vitro and animal studies evaluating the effect of hyperbaric oxygen on the growth features of Candida albicans support this result (29,30).

Although our study primarily observed symptomatic effects, with significant changes found only in subjective VAS scores for dry mouth and halitosis, it provides a promising foundation for future studies. Future research can build upon our study's findings to explore the potential beneficial effects of hyperbaric oxygen therapy in improving diabetes-associated oral manifestations by including objective parameters such as saliva viscosity, oral bacterial flora, and periodontal measurements in a larger patient group.

CONCLUSION

In conclusion, diabetes mellitus can lead to severe complications, including oral health problems due to high blood glucose levels. The lack of care, insufficient measures, and unawareness of diabetes-related factors contribute to poor diabetic control. Uncontrolled blood glucose levels generate serious health problems related to insufficient foot and oral care. The present study shows that hyperbaric oxygen therapy positively affects subjective symptoms, such as dry mouth and halitosis, in diabetic patients with foot ulcers. Future studies with larger sample sizes and the addition of parameters such as saliva viscosity will expand the use of HBO2 in dentistry.

Conflict of Interest

None.

Acknowledgements None.

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