Role of Low-Level Laser Therapy as an Adjunct to Initial Periodontal Treatment in Type 2 Diabetic Patients: A Split-Mouth,Randomized,Controlled Clinical Trial

Abstract

Objective: In this split-mouth clinical trial, we evaluated the clinical benefits of low-level laser therapy (LLLT) as an adjunct to nonsurgical periodontal treatment in patients with type 2 diabetes mellitus (DM). Background data: The impaired wound healing seen in diabetic patients may affect the results of periodontal treatment and may require an additional approach. Materials and methods: In total, 22 chronic periodontitis patients with type 2 DM were included. Applying a split-mouth design, two quadrants were treated with only scaling and root planing (SRP) as the control and those in the other two were treated with SRP + LLLT as the test sites in each patient. An 808 nm GaAlAs diode laser was performed in the test sites at the energy density of 4.46 J/cm² on days 1, 2, and 7 after SRP. Plaque index (PI), probing depth (PD), bleeding on probing (BOP), and clinical attachment level were measured at baseline and again at 1 and 3 months after treatment. Deep periodontal pockets (PD ≥4 mm) were evaluated separately. Results: Test sites showed significant improvement in PI and BOP in deep pockets at the 1-month follow-up period (p < 0.001 and <0.001, respectively), whereas no difference was found between the control and the test sites in other periodontal parameters. Conclusions: LLLT during periodontal treatment offered minimal short-term additional benefit in deep pocket healing in patients with type 2 DM.

Introduction

Diabetes Mellitus (DM) is caused by a deficiency in insulin or its action, resulting in hyperglycemia and hyperlipidemia, which are involved in the development of many systemic and oral complications, such as periodontitis.^1,2 Studies have shown that type 2 DM is a risk factor for periodontal diseases and those patients with diabetes show higher prevalence and severity of periodontitis compared with nondiabetic patients.^3
–5 The impaired wound healing seen in diabetic patients may affect the results of periodontal treatment and may require an additional approach. According to the evidence, low-level laser therapy (LLLT), also called photobiomodulation, has potential utility in accelerating the inflammatory response of wound healing. Clinical studies have shown that LLLT promotes wound healing by accelerating inflammation,⁶ collagen synthesis,⁷ healing time, and strength acquisition.⁸ Further, the studies about LLLT as a treatment method for diabetic ulcers have shown positive results.^9
–11 In a previous study, the effects of LLLT as an adjunct to nonsurgical periodontal treatment in periodontal wound healing in smokers and nonsmokers with chronic periodontitis were evaluated and that previous study indicated that LLLT, as an adjunctive therapy to nonsurgical periodontal treatment, improved periodontal healing.¹² In the current study, because DM, like smoking, affects the healing of periodontal tissues, it was hypothesized that LLLT would have positive effects on the microcirculation and on collagen and cytokine production, which are negatively affected by DM. Thus, the purpose of this split-mouth, randomized, controlled clinical trial was to evaluate the effects of LLLT as an adjunct to nonsurgical periodontal treatment on clinical parameters in type 2 DM patients with chronic periodontitis.

Materials and Methods

The study was approved by the Research Ethics Committee of Istanbul University of Medical Sciences (protocol number: 2012/1467/1223). Written informed consent was obtained from all patients before their enrollment in the study. The study protocol was approved and registered under International Clinical Trials Registry Platform with the Thai Clinical Trials Registry, TCTR20150730001.

Between October 2013 and February 2014, 80 type 2 DM patients being followed as outpatients in the Department of Endocrinology, Istanbul Medical Faculty, Istanbul University, were screened. Patients who had type 2 DM were selected and classified based on the criteria of the American Diabetic Association (2011) and glycated hemoglobin levels (HbA1C).¹³ All diabetic patients were followed up regularly in the department of endocrinology and all had stable diabetes. Among the type 2 DM patients, 22 patients with moderate to severe chronic periodontitis were selected for the study,¹⁴ and periodontal disease severity was defined according to Page and Eke.¹⁵

Exclusion criteria were any kind of periodontal treatment during the last 6 months or use of antibiotics during the last 3 months, smoking, acute oral or systemic infection, periodontal abscess, hemorrhagic disorders, autoimmune diseases, pregnancy, or <15 teeth and partial dentures. Teeth with fixed prosthodontics, and a mobility grade of III or pockets deeper than 10 mm in the studied areas were not evaluated.

All patients received oral hygiene instructions and supragingival scaling in two appointments, 1 week apart, before root planing treatment. Full-mouth subgingival scaling and root planing (SRP) under local anesthesia (Ultracain DS; Aventis Pharmacheuticals, Istanbul, Turkey) was performed by the same operator in a single appointment for each patient in all groups using hand instruments (Gracey Curets; Hu-Friedy, Chicago, IL) and ultrasonic devices (Cavitron; Dentsply, York, PA).

The study was performed according to a split-mouth design, and each patient was included in a clinical protocol consisting of two different modalities: teeth were treated by SRP alone (control site) and by SRP followed by LLLT (test site). Two quadrants were randomly assigned to the control and two to the test group for each patient. Randomization was performed using a computer-generated random allocation table. Each selected segment first received a code number, and one of the study coordinators used a computer-generated table to randomly allocate each quadrant to the SRP (control, n = 22) or SRP + LLLT (test, n = 22) group.

A GaAlAs diode laser (λ = 808 nm, Fotona XD-2; FOTONA D.O.O., Ljubljana, Slovenia) was used in this study. The laser (output power, 0.25 W; continuous mode; handpiece, R24-B; spot diameter, 6 mm; spot size, 0.28 cm²) was applied with noncontact technique to the root surfaces through the labial and oral gingiva at the test sites after the periodontal treatment. The parameters^16

–20 applied in the protocol are described in Table 1.

Table 1.

Parameters of LLLT

Energy per point/per tooth	1.25/5 J
Power density	0.89 W/cm²
Energy density/per point	4.46 J/cm²
Duration of each point	5 sec
Four points/per gingiva of root surface	20 sec
Frequency of the treatment	3 times (days 1, 2, and 7)
Cumulative dose for 3 days	13.38 J/cm²

LLLT, low-level laser therapy.

Clinical periodontal parameters were bleeding on probing (BOP), plaque index (PI),²¹ gingival index (GI),²² probing depth (PD), and clinical attachment level (CAL). The primary outcome was BOP changes in deep pockets of the test and control sites over the 3-month follow-up period. PI, GI, PD, and CAL were our secondary outcomes. All measurements were recorded at six sites per tooth (mesio-, mid-, and disto-vestibular, and mesio-, mid-, and disto-palatal) at baseline and at 1 and 3 months after treatment with a periodontal Williams probe (PW6; Hu-Fredy, Chicago, IL), calibrated in millimeters. The cemento–enamel junction was used as a reference point. A trained dentist, who was blinded to the treatment received by the patients, conducted periodontal examinations.

Statistical analysis

For sample size calculation, BOP% was used as the primary outcome variable. According to the results of the power analysis, a sample size of 80 quadrants in 20 participants was identified for 80% statistical power, β = 0.20, and α = 0.05 (to detect Δ = 10%).

The data collected were analyzed using a statistical software package (SPSS, version 15.0; SPSS, Chicago, IL). Sites were divided into two subgroups according to initial PD²³: shallow pockets (0–3 mm); moderate and deep pockets (4–10 mm). Differences between test and control sites and between different time points were analyzed using the Mann–Whitney U test and Wilcoxon signed-rank test, respectively. Statistical significance was set at the 99% confidence level (p < 0.01) for the Mann–Whitney U test and 95% (p < 0.05) for the Wilcoxon signed-rank test.

Results

Descriptive results

Twenty-two participants attended the baseline examination, treatment, and the follow-up appointments over a 3-month period. The total numbers of test and control sites were 1518 and 1548, and the test and control sites with PD ≥4 mm were 698 and 669, respectively. Demographic variables described in Table 2.

Table 2.

Descriptive Parameters of the Study Group

No. of patients	22
Mean age (min/max years) (mean ± SD)	41/72, 50.50 ± 8.72
Female (n, %)	15, 68.2
Male (n, %)	7, 31.8
Pocket depth ≥4 mm (%)	44.5, 22.7 (test)/21.8 (control)
Diabetes duration (min/max years) (mean ± SD)	3/13, 5.40 ± 2.55
HbAIc at baseline (%) (min/max) (mean ± SD)	5.50/10.90, 7.45 ± 1.43
Oral antidiabetic therapy (n, %)	15, 68.2
Oral antidiabetic + insulin therapy (n, %)	7, 31.8

SD, standard deviation.

Clinical parameters

There was no statistically significant difference in the clinical baseline measurements (PI, BOP, PD, and CAL) between the test and control sites (Table 3). Within the sites, statistically significant improvements (p < 0.05) were noted for PI, BOP, PD, and CAL when baseline values were compared with the 3-month follow-up evaluation (Table 3). The improvements in these clinical parameters were slightly better in the test sites, but the differences were not statistically significant (p > 0.01).

Table 3.

Differences in Clinical Parameters

Parameter mean ± SD	Baseline	1 Month	Difference (0- to 1-month)	p^*	3 Months	Difference (0- to 3-month)	p^†
PI
Test	1.81 ± 0.36	0.91 ± 0.39	0.89 ± 0.38	0.000	0.74 ± 0.26	1.06 ± 0.31	0.000
Control	1.78 ± 0.36	1.06 ± 0.32	0.71 ± 0.34	0.000	0.81 ± 0.20	0.97 ± 0.34	0.000
p ^*			0.122			0.364
BOP (mm)
Test	0.88 ± 0.11	0.39 ± 0.17	0.49 ± 0.15	0.000	0.33 ± 0.15	0.54 ± 0.17	0.000
Control	0.87 ± 0.14	0.44 ± 0.16	0.43 ± 0.16	0.000	0.33 ± 0.16	0.54 ± 0.19	0.000
p ^*			0.225			0.954
PD (mm)
Test	3.94 ± 0.68	2.80 ± 0.58	1.13 ± 0.31	0.000	2.74 ± 0.54	1.20 ± 0.53	0.000
Control	3.86 ± 0.57	2.79 ± 0.56	1.06 ± 0.23	0.000	2.69 ± 0.46	1.16 ± 0.30	0.000
p ^*			0.395			0.769
CAL (mm)
Test	4.30 ± 1.01	3.10 ± 0.89	1.20 ± 0.34	0.000	3.14 ± 0.98	1.16 ± 0.89	0.000
Control	3.91 ± 1.06	2.99 ± 0.73	0.92 ± 0.75	0.000	2.89 ± 0.62	1.02 ± 0.78	0.000
p ^*			0.123			0.573

Mann–Whitney U test, p < 0.01.

†

Wilcoxon test, p < 0.05.

BOP, bleeding on probing; CAL, clinical attachment level; PD, probing depth; PI, plaque index.

The clinical measurements of deep pockets were analyzed and are shown in Table 4. BOP and PI scores showed statistically significant improvements in the test sites between baseline and the first month. The reduction in PI was also significantly greater in the test than in the control sites between baseline and the third month. There was no significant difference between control and test sites in PD or CAL changes at follow-up.

Table 4.

Differences in Clinical Parameters (>4 mm PD)

Parameter mean ± SD	Baseline	1 Month	Difference (0- to 1-month)	p^*	3 Months	Difference (0- to 3-month)	p^†
PI
Test	1.98 ± 0.60	1.02 ± 0.86	0.95 ± 0.93	0.000	0.87 ± 0.80	1.11 ± 0.88	0.000
Control	1.96 ± 0.60	1.25 ± 0.82	0.71 ± 0.90	0.000	0.97 ± 0.78	0.99 ± 0.92	0.000
p ^*			0.000			0.000
BOP (mm)
Test	0.94 ± 0.23	0.48 ± 0.50	0.46 ± 0.51	0.000	0.40 ± 0.49	0.54 ± 0.52	0.000
Control	0.93 ± 0.26	0.59 ± 0.49	0.33 ± 0.52	0.000	0.40 ± 0.49	0.52 ± 0.54	0.000
p ^*			0.000			0.657
PD (mm)
Test	5.31 ± 1.08	3.37 ± 1.28	1.93 ± 1.09	0.000	3.17 ± 1.19	2.14 ± 1.14	0.000
Control	5.30 ± 0.96	3.41 ± 1.23	1.88 ± 1.14	0.000	3.24 ± 1.15	2.05 ± 1.11	0.000
p ^*			0.808			0.337
CAL (mm)
Test	5.73 ± 1.45	3.90 ± 1.65	1.94 ± 1.13	0.000	3.60 ± 1.51	2.13 ± 1.19	0.000
Control	5.53 ± 1.15	3.68 ± 1.42	1.90 ± 1.15	0.000	3.48 ± 1.34	2.04 ± 1.14	0.000
p ^*			0.854			0.255

Mann-Whitney U test, p < 0.01.

†

Wilcoxon test, p < 0.05.

Discussion

LLLT has been shown to be an effective modality in patients who suffer from diabetic wounds, especially for diabetic foot ulcers.¹⁰ Research findings to date, based on in vitro animal and human studies, have shown that LLLT can play a useful role in healing chronic diabetic ulcers resistant to conventional treatments.^9,24 The use of LLLT in periodontal treatment is still controversial. One study has shown no additional benefit,²⁵ whereas others have shown that LLLT has demonstrable clinical efficacy, including our previous study that showed additional improvement in smokers.^12,26

–29 The present study was conducted from the perspective that more dramatic changes may occur among patients with impaired wound healing, such as those with diabetes mellitus (DM).

Limited clinical research was found in the literature when the search was focused on adjunctive effects of LLLT during the periodontal therapy in patients with DM2.^30,31 Although there were methodological differences with our study, two studies reported that the effects of LLLT on periodontal tissues were mediated by DM.^30,31 A histological study conducted by Obradović et al.³⁰ reported that more pronounced signs of gingival tissue healing were observed after applying LLLT (670 nm, 2 J/cm²) as an adjunct to nonsurgical periodontal treatment in patients with type 1 and type 2 DM. A subsequent study evaluated the effects of LLLT by exfoliative cytology in patients with DM and gingival inflammation; more pronounced GI reduction and lower cellular parameters were noticed on the laser-treated side of the jaw than on the nonlaser side.³¹

The present study was designed to evaluate the role of LLLT as an adjunct to nonsurgical periodontal treatment in deep pockets among patients with type 2 DM. When deep pockets were compared, test sites showed significant improvements in BOP between baseline and 1 month. LLLT has been shown to be effective in the treatment of impaired microcirculation, reducing inflammation, and swelling. Moreover, it can facilitate collagen synthesis, angiogenesis, and reepithelialization, which eventually accelerate wound healing.^32
–34 Thus, the greater reduction in gingival bleeding in deep pockets at the test sites can be explained by the anti-inflammatory effect of vascular stimulation by the LLLT. Considering that the improvement was present at the 1-month follow-up, but not later, it is thought that LLLT may have reduced inflammation in the initial healing of the wounds and attachment of junctional epithelium.

When all pocket depths were analyzed, the test sites did not show any additional improvement compared with the control sites, as measured by any of the periodontal clinical parameters examined (PI, BOP, PD, and CAL). Some studies have investigated the use of LLLT as an adjunct in nonsurgical periodontal treatment in systemically healthy patients.^12,27
–29 These studies reported that LLLT as an adjunct to periodontal treatment showed significant clinical improvements. Insufficient irradiation may have been the cause of poor results in some studies due to the lack of consensus about dosage.³⁵ In this study, the LLLT was administered on days 1, 2, and 7 after the initial periodontal treatment at an energy density of 4.46 J/cm². Although we found significant enhancement in BOP parameters between the baseline and 1 month, the effects of treatment on other clinical parameters were not significant. This might have been due to insufficient irradiation. Although their patients were not diabetic, Pejcic et al. reported that the effect of LLLT was more pronounced after the fifth application of the laser;²⁹ further, Obradović et al. achieved positive effects after five consecutive applications of LLLT in DM patients.³¹ This limitation might also explain why significant BOP reduction in the first month of the test sites was not maintained to the third month. Thus, given these results, there is a need to evaluate the effects of different dosages on periodontal tissues in diabetic patients. Further studies are also required to establish optimal treatment protocols, such as wavelength, fluency, intensity, exposure time, and total duration of the treatment.

Conclusions

This split-mouth, randomized clinical trial indicated that the use of a low-level laser as an adjunct to SRP showed a minor short-term additional benefit on gingival bleeding, but it did not significantly enhance other clinical parameters.

Footnotes

Acknowledgments

This work was supported by the Scientific Research Projects Coordination Unit of Istanbul University, project number; T-39791. The authors declare that there are no conflicts of interest in this study. No external funding, apart from the support of the authors' institutions, was available for the study.

Author Disclosure Statement

No competing financial interests exist.

References

Mealey

, Ocampo

. Diabetes mellitus and periodontal disease. Periodontol 2000, 2007; 44:127–153.

Taylor

, Borgnakke

. Periodontal disease: associations with diabetes, glycemic control and complications. Oral Dis, 2008; 14:191–203.

Khader

, Dauod

, El-Qaderi

, Alkafajei

, Batayha

. Periodontal status of diabetics compared with non-diabetics: a meta-analysis. J Diabetes Complications, 2006; 20:59–68.

Taylor

, Burt

, Becker

. Non-insulin dependent diabetes mellitus and alveolar bone loss progression over 2 years. J Periodontol, 1998; 69:76–83.

Tsai

, Hayes

, Taylor

. Glycemic control of type 2 diabetes and severe periodontal disease in the US adult population. Community Dent Oral Epidemiol, 2002; 30:182–192.

Mester

, Mester

. The biomedical effects of laser application. Lasers Surg Med, 1985; 5:31–39.

Pereira

, Eduardo Cde

, Matson

, Marques

. Effect of low-power laser irradiation on cell growth and pro-collagen synthesis of cultured fibroblasts. Lasers Surg Med, 2002; 31:263–267.

Broadley

, Broadley

, Disimone

, Riensch

, Davidson

. Low-energy helium-neon laser irradiation and the tensile strength of incisional wounds in the rat. Wound Repair Regen, 1995; 3:512–517.

Kaviani

, Djavid

, Ataie-Fashtami

, et al. A randomized clinical trial on the effect of low-level laser therapy on chronic diabetic foot wound healing: a preliminary report. Photomed Laser Surg, 2011; 29:109–114.

10.

Beckmann

, Meyer-Hamme

, Schroder

. Low level laser therapy for the treatment of diabetic foot ulcers: a critical survey. Evid Based Complement Alternat Med, 2014; 2014:626127.

11.

, Naim

, Lanzafame

. Effects of photostimulation on wound healing in diabetic mice. Lasers Surg Med, 1997; 20:56–63.

12.

Aykol

, Baser

, Maden

, et al. The effect of low-level laser therapy as an adjunct to non-surgical periodontal treatment. J Periodontol, 2011; 82:481–488.

13.

Diagnosis and classification of diabetes mellitus. Diabetes Care, 2011; 34:62–69.

14.

Armitage

. Development of a classification system for periodontal diseases and conditions. Ann Periodontol, 1999; 4:1–6.

15.

Page

, Eke

. Case definitions for use in population-based surveillance of periodontitis. J Periodontol, 2007; 78:1387–1399.

16.

Enwemeka

. Standard parameters in laser phototherapy. Photomed Laser Surg, 2008; 26:411–412.

17.

Enwemeka

. Intricacies of dose in laser phototherapy for tissue repair and pain relief. Photomed Laser Surg, 2009; 27:387–393.

18.

Huang

, Chen

ACH

, Carroll

, Hamblin

. Biphasic dose response in low level light therapy. Dose Response, 2009; 7:358–383.

19.

Jenkins

, Carroll

. How to report low-level laser therapy (LLLT)/photomedicine dose and beam parameters in clinical and laboratory studies. Photomed Laser Surg, 2001; 29:785–787.

20.

WALT. Standards for the design and conduct of systematic reviews with low-level laser therapy for musculoskeletal pain and disorders. Photomed Laser Surg, 2006; 24:759–760.

21.

Silness

, Loe

. Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal conditions. Acta Odontol Scand, 1964; 22:121–135.

22.

Loe

, Silness

. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol Scand, 1963; 21:533–551.

23.

Brown

, Oliver

, Loe

. Periodontal diseases in the U.S. in 1981: prevalence, severity, extent, and role in tooth mortality. J Periodontol, 1989; 60:363–370.

24.

Houreld

, Sekhejane

, Abrahamse

. Irradiation at 830 nm stimulates nitric oxide production and inhibits pro-inflammatory cytokines in diabetic wounded fibroblast cells. Lasers Surg Med, 2010; 42:494–502.

25.

Ribeiro

, Sbrana

, Esper

, Almeida

. Evaluation of the effect of the GaAlAs laser on subgingival scaling and root planing. Photomed Laser Surg, 2008; 26:387–391.

26.

Qadri

, Miranda

, Tunér

, Gustafsson

. The short-term effects of low-level lasers as adjunct therapy in the treatment of periodontal inflammation. J Clin Periodontol, 2005; 32:714–719.

27.

Makhlouf

, Dahaba

, Tunér

, Eissa

, Harhash

. Effect of adjunctive low level laser therapy (LLLT) on nonsurgical treatment of chronic periodontitis. Photomed Laser Surg, 2012; 30:160–166.

28.

Dukić

, Bago

, Aurer

, Roguljić

. Clinical effectiveness of diode laser therapy as an adjunct to non-surgical periodontal treatment: a randomized clinical study. J Periodontol, 2013; 84:1111–1117.

29.

Pejcic

, Kojovic

, Kesic

, Obradovic

. The effects of low level laser irradiation on gingival inflammation. Photomed Laser Surg, 2010; 28:69–74.

30.

Obradović

, Kesić

, Mihailović

et al. A histological evaluation of a low-level laser therapy as an adjunct to periodontal therapy in patients with diabetes mellitus. Lasers Med Sci, 2013; 28:19–24.

31.

Obradović

, Kesić

, Mihailović

, Jovanović

, Antić

, Brkić

. Low level lasers as an adjunct in periodontal therapy in patients with diabetes mellitus. Diabetes Technol Ther, 2012; 14:799–803.

32.

Marques

, Pereira

, Fujihara

, Nogueira

, Eduardo

. Effect of low-power laser irradiation on protein synthesis and ultrastructure of human gingival fibroblasts. Lasers Surg Med, 2004; 34:260–265.

33.

Hawkins

, Abrahamse

. Effect of multiple exposures of low-level laser therapy on the cellular responses of wounded human skin fibroblasts. Photomed Laser Surg, 2006; 24:705–714.

34.

Silveira

, Streck

, Pinho

. Evaluation of mitochondrial respiratory chain activity in wound healing by low-level laser therapy. J Photochem Photobiol B, 2007; 86:279–282.

35.

Posten

, Wrone

, Dover

, Arndt

, Silapunt

, Alam

. Low-level laser therapy for wound healing: mechanism and efficacy. Dermatol Surg, 2005; 31:334–340.