Pyruvate-lactate reaction of the body to combined laser irradiation and transcanal electrophoresis of copper-calcium in patients with type 2 diabetes and periodontitis

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BACKGROUND

The pandemic of type 2 diabetes mellitus (T2DM) has emerged as a serious public health threat [1–3]. The persistent upward trend in T2DM prevalence is complicated by worsening oral health in these patients, with edentulism rates up to 15 times higher [2]. Increasing evidence indicates that, in addition to glycemic risks, diabetes is associated with comorbidities including dental diseases [1–3]. The concept of “metabolic memory”—where early glycemic exposure causes long-term disruptions in target tissues even after optimal glucose control—underscores the clinical imperative for early risk identification and management of comorbidities. In recent years, various physiotherapy techniques have been increasingly applied to treat conditions such as metabolic syndrome and associated dental diseases [4–9]. However, combined transcanal electrophoresis of copper-calcium and laser irradiation have not previously been used to treat T2DM with endodontic–periodontal lesions.

AIM

This study aimed to improve the clinical efficacy of dental treatment in T2DM patients with endodontic–periodontal lesions by using adjunctive transcanal electrophoresis of copper-calcium and low-level laser irradiation (LLLT), with assessment criteria including lactate–pyruvate response and dental status.

METHODS

A randomized, open-label clinical trial was conducted with 165 T2DM patients; 123 of them were confirmed to have endodontic–periodontal lesions, which is consistent with an average 75% prevalence of dental disease in 40- to 70-year-old T2DM adults [1, 2, 4, 5].

The research was conducted in accordance with the ethical standards of the Declaration of Helsinki (as amended in 2013) under ethical approval No. 24 (2022, Peoples’ Friendship University of Russia).

Participants with T2DM (59 men, 47.9%; 64 women, 52.1%) underwent confirmation of endodontic–periodontal lesions via medical and dental history [6, 7], oral examination, and dynamic laboratory assessment of gluconeogenesis metabolites, i.e., blood pyruvate and lactate levels [8–10]. Blood samples were drawn from the antecubital vein, centrifuged for 5 minutes at 1700 g, and analyzed using an enzymatic colorimetric Lactate/Pyruvate assay [LOX-PAP, Biocom, Germany]. The analyte concentrations were measured with a PE-5300VI spectrophotometer. Working length in affected teeth was measured using an electronic apex locator (Dentaport ZX RCM-EX, Japan) [10–12].

Inclusion Criteria: T2DM patients aged 40–70 with confirmed endodontic–periodontal lesions who provided informed consent.

Non-inclusion Criteria: Age < 40 or > 70, severe T2DM complications, intolerance to electrophysiological procedures or copper/calcium or laser irradiation [13–15].

Exclusion Criteria: Non-adherence to the treatment protocol. Before the administration of the medication via transcanal delivery (transcanal electrophoresis [16]) and prior to final obturation, root canals were treated transcanally using laser irradiation (λ = 810 nm) and a 3% sodium hypochlorite solution.

Intervention

The study included 123 patients with T2DM and confirmed endodontic–periodontal lesions. Clinical and laboratory evaluations were conducted at the City Endocrinology Department in Moscow and the rehabilitation unit of the Victoria Sanatorium. Assessments focused on height, weight, body mass index, and consultations with an endocrinologist, dentist, and physiotherapist. Dental status was evaluated by radiographic imaging (panoramic radiography), and laboratory assessment included plasma levels of pyruvate and lactate as potential targets for non-pharmacologic transcanal laser and copper-calcium drug electrophoresis [16]. Before transcanal administration of the drug (endodontic electrophoresis) and final obturation, root canals were treated with transcanal laser irradiation (λ = 810 nm) and 3% sodium hypochlorite. Parameters of transcanal LLLT were: 810 nm wavelength with continuous laser mode; 80–1200 Hz pulse frequency; 30–120 s exposure duration per field, with a power flux density of 15–20 mW/cm².

Lactate and pyruvate levels were selected as diagnostic markers and potential targets for combined transcanal laser exposure and electrophoresis of copper-calcium [17].

In all patients, body mass index was calculated and the severity of metabolic disturbances was assessed using plasma levels of lactate (L) and pyruvate (P) (mmol/L). The L:P ratio was also calculated to compare with normal physiologic levels. All T2DM patients with endodontic–periodontal lesions exhibited metabolic disturbances, evidenced by radiologic signs in the periodontium and elevated plasma lactate and glycated methemoglobin (HbA1c) levels, combined with reduced pyruvate values and an altered physiological ratio between them [18–20].

RESULTS

The distribution of patients across the study groups by severity of T2DM and diagnosed endodontic–periodontal lesions (n = 123, abs./% of total) is shown in Table 1.

 

Table 1. Patients with DM-2 and diagnosed periodontal periodontitis

Groups	Sex (abs., %)				Dental disease
	M	F	T2DM severity		Periodontitis	Periapical periodontitis and caries
Group 1	15 (12.2)	16 (13.0)	Mild	17 (54.8)	17 (13.8)	39 (31.7)
			Moderate	11 (36.6)
			Severe	1 (3.4)
Group 2	15 (12.2)	16 (13.0)	Mild	16 (51.6)	16 (13.0)	34 (27.6)
			Moderate	13 (41.9)
			Severe	2 (6.5)
Group 3	15 (12.2)	16 (13.0)	Mild	16 (51.6)	15 (12.2)	32 (26.0)
			Moderate	13 (41.9)
			Severe	2 (6.6)
Group 4	14 (11.4)	16 (13.0)	Mild	13 (43.3)	17 (13.8)	32 (26.0)
			Moderate	15 (50.0)
			Severe	3 (10.0)

 Note. All groups are comparable in terms of diabetes mellitus severity, gender (p >0.05), and dental pathology (p >0.05). DM-2 — diabetes mellitus type 2.

 

Significant shifts in baseline lactate levels were found in 75 patients (61.0%), with lactate levels exceeding the normal reference range by 2.9 times (p < 0.05) and pyruvate levels falling 33.6% below the lower limit of the reference range (p < 0.01) (Table 2).

 

Table 2. Blood lactate and pyruvate levels in DM-2 patients with periodontal pathology before and after physiotherapy treatment (n=123)

Parameter	Group 1	Group 2	Group 3	Group 4
Before treatment
Lactate, mmol/L	2.97 [2.88; 3.16]	2.8 [2.6; 3.05]	2.89 [2.68; 3.09]	2.86 [2.65; 3.17]
After treatment
Lactate, mmol/L	1,9 [1, 8; 2, 0]##••	2,5 [2, 3; 2, 75]*	2,4 [2, 3; 2, 59]*	2,6 [2, 5; 2, 7]*
Reference range: 0.95–1.8 mmol/L
Before treatment
Pyruvate, mmol/L	0,04 [0, 03; 0, 048]	0,0379 [0, 028; 0, 043]	0,037 [0, 03; 0, 044]	0,026 [0, 02; 0, 032]
After treatment
Pyruvate, mmol/L	0,058 [0, 05; 0, 068]#	0,04 [0, 038; 0, 045]*	0,048 [0, 04; 0, 053]	0,046 [0, 04; 0, 052]
Reference range: 0.05–0.06 mmol/L
Before treatment
L:P (units)	54.8 [51.7; 57.9]	61.8 [60.8; 62.8]	58.4 [57.3; 59.6]	56.8 [54.5; 59.1]
After treatment
L:P (units)	31.6 [30.7; 32.6]*	59.8 [58.8; 60.7]**	58.0 [57.3; 58.9]**	55.4 [54.5; 56.4]**
Reference range: 19.0–20.5 mmol/L

Note. LC — blood lactate; PVC — blood pyruvate. The data is presented by Me [Q₁; Q₃]. The reliability in each group before and after treatment according to the Wilcoxon criterion: ^# — p <0.05; ^## — p <0.01. The reliability between the groups in relation to the 4th group without physiotherapy after treatment according to the Kraskel–Wallis criterion: ^• — p <0.05; ^•• — p <0.01.

 

After combined treatment, pyruvate levels increased and lactate levels decreased, leading to an improvement in the L:P ratio from 54.8 [51.7; 57.9] to 31.6 [30.7; 32.6] units (p < 0.05), demonstrating correction of hypoxia and acid–base imbalance in the tissues. The most pronounced positive changes were observed in group 1 patients who received transcanal laser therapy of the root structures of affected teeth followed by transcanal electrophoresis of copper-calcium. Correction of tissue hypoxia and acidosis enhances the efficacy of decontamination in chronic oral infection foci and improves the adaptive capacity of patients with T2DM.

Participants

The study enrolled 123 patients with T2DM (59 men and 64 women), all diagnosed with endodontic–periodontal lesions. Significant baseline deviations were observed: serum lactate levels were 2.9-fold above the reference range (p < 0.05), and pyruvate levels were 33.6% below normal (p < 0.01), reflecting pronounced anaerobic shifts amid acid–base imbalance in the tissues. In group 1 (transcanal laser irradiation of affected root structures followed by copper-calcium electrophoresis), the L:P ratio improved significantly from 54.8 [51.7; 57.9] to 31.6 [30.7; 32.6] units (p < 0.05), indicating correction of tissue hypoxia and acid–base disturbance.

Significant baseline shifts in blood lactate levels were identified in 75 patients (61.0%), with concentrations exceeding the reference range by 2.9 times (p < 0.05) and pyruvate levels decreased by 33.6% below the reference range (p < 0.01). In 56.5% of patients with T2DM, manifestations of endodontic–periodontal lesions (exudative, hemorrhagic, and proliferative forms) included marked cyanosis of the gingival margin, friability of the interdental papillae accompanied by granulation tissue protruding from the papillae, and purulent or hemorrhagic exudate. In 30.6% of patients with T2DM, periodontal changes were characterized by gingival collar-like encasement of the tooth necks and bulbous swelling of the interdental papillae, more frequently observed in individuals with severe disease progression. All patients with T2DM in the study exhibited a marked elevation in lactate levels, whereas pyruvate levels were significantly reduced to 33.6% below the reference range (p < 0.01), indicating pronounced anaerobic shifts associated with T2DM-related metabolic disturbances. Following combination therapy, an increase in pyruvate concentration and a decrease in lactate levels were observed, contributing to the improvement of the physiological L:P ratio from 54.8 [51.7; 57.9] to 31.6 [30.7; 32.6] units (p < 0.05), indicating resolution of tissue hypoxia. Prior to dental treatment, it is essential to conduct a thorough evaluation of patients with T2DM, assessing not only their dental status but also identifying potential targets of metabolic imbalance—specifically pyruvate and lactate levels—to mitigate dental complications and glycemic risks.

Statistical Analysis

Data were processed using Microsoft Excel (2017) and IBM SPSS Statistics 26 (PASW Statistics 2018). Descriptive statistics included mean ± standard deviation, interquartile ranges (Q1; Q3), histograms, and box plots. Normality of distribution was assessed via descriptive metrics and the Shapiro–Wilk test. Changes in glycemic control and HbC% were analyzed using repeated-measures ANOVA (general linear model). Absolute and relative variables were compared using the Student’s t-test (p < 0.05). For comparison of independent groups with non-normal distribution across more than two groups, the Kruskal–Wallis test was used. When comparing two dependent groups, the Wilcoxon signed-rank test was applied. To compare with the control group, the Mann–Whitney U test was used. Changes in the studied parameters during treatment were assessed using the Wilcoxon signed-rank test for paired samples with non-normal distribution. Correlations between age (predictor) and the studied parameters (outcomes) were assessed using the Spearman’s correlation coefficient for groups with non-normal distributions and the Pearson’s correlation coefficient for normally distributed data.

DISCUSSION

The present study highlights the importance of assessing not only the dental status of patients with T2DM but also their acid–base balance markers, specifically blood pyruvate and lactate, which reflect the degree of tissue hypoxia and oxidative stress within the dentoalveolar complex.

In T2DM patients who received adjuvant transcanal laser irradiation of affected tooth root structures followed by transcanal copper-calcium electrophoresis, a more rapid restoration of damaged dental and periodontal tissues was observed. This recovery was associated with normalization of the L:P ratio and a reduction in glycemic risks.

Additionally, this therapeutic protocol enhanced reparative and adaptive responses in the tissues of patients receiving transcanal copper-calcium electrophoresis alone.

It is well established that LLLT provides significant microvascular, antioxidant, and anti-inflammatory benefits [11–18]. Therefore, it may be concluded that laser therapy exerts significant anti-inflammatory and disinfecting effects in the complex root canal systems of affected teeth, supporting enhanced tissue healing, particularly after the administration of a therapeutic copper-calcium depot.

CONCLUSION

In summary, combined physiotherapy in T2DM patients with endodontic–periodontal lesions reduces the risk of inflammatory complications and improves clinical outcomes. The mitigation of tissue hypoxia and acidosis enhances the efficacy of infection control measures for chronic oral foci, ultimately contributing to increased adaptive capacity. Following combination therapy, patients demonstrated reduced severity of metabolic disturbances and hypoxic events, as evidenced by improved physiological L:P ratios.

ADDITIONAL INFORMATION

Funding source. This study was not supported by any external sources of funding.

Competing interests. The authors declare that they have no competing interests.

Author’s сontribution. All authors made a substantial contribution to the conception of the work, acquisition, analysis, interpretation of data for the work, drafting and revising the work, final approval of the version to be published and agree to be accountable for all aspects of the work. T. Chkheidze — collection of material; A.S. Tkachenko — statistical processing, editorial; N.G. Kulikova — writing, editorial.

Patients’ consent. Written consent obtained from all the study participants before the study screening in according to the study protocol approved by the local ethic committee.

ДОПОЛНИТЕЛЬНАЯ ИНФОРМАЦИЯ

Источник финансирования. Авторы заявляют об отсутствии внешнего финансирования при проведении исследования и подготовке публикации.

Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с проведенным исследованием и публикацией настоящей статьи.

Вклад авторов. Все авторы подтверждают соответствие своего авторства международным критериям ICMJE (все авторы внесли существенный вклад в разработку концепции, проведение исследования и подготовку статьи, прочли и одобрили финальную версию перед публикацией). Наибольший вклад распределён следующим образом: Т. Чхеидзе — сбор материала; А.С. Ткаченко — статистическая обработка, редакция; Н.Г. Куликова — написание, редакция.

Информированное согласие на участие в исследовании. Все участники до включения в исследование добровольно подписали форму информированного согласия, утверждённую в составе протокола исследования этическим комитетом.

About the authors

Natalia G. Kylikova

I.M. Sechenov First Moscow State Medical University; Peoples' Friendship University of Russia named after Patrice Lumumba

Author for correspondence.
Email: kulikovang777@mail.ru
ORCID iD: 0009-0007-0374-6763
SPIN-code: 6613-1164

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow; 6 Miklukho-Maklaya st, Moscow, 117198

Tinatin B. Chkheidze

Peoples' Friendship University of Russia named after Patrice Lumumba

Email: tinatin@mail.ru
ORCID iD: 0000-0003-1797-1324
SPIN-code: 4134-4069
Russian Federation, 6 Miklukho-Maklaya st, Moscow, 117198

Albina S. Tkachenko

Peoples' Friendship University of Russia named after Patrice Lumumba

Email: rocstar-fo@to.ru
ORCID iD: 0000-0001-8506-8562
SPIN-code: 6126-1475

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, 6 Miklukho-Maklaya st, Moscow, 117198

References

Supplementary files