Photobiomodulation, Photomedicine, and Laser Surgery

Volume 38, Number 3, 2020 Photobiomodulation Review—

ª Mary Ann Liebert, Inc.
Pp. 138–144 Original Research
DOI: 10.1089/photob.2019.4714

Effect of Modified Laser Transcutaneous Irradiation on Pain

and Quality of Life in Patients with Diabetic Neuropathy

Milena Valdinéia da Silva Leal, DDS, PhD,1 Mário Oliveira Lima, PhD,2 Renata Amadei Nicolau, PhD,1,3
Teresa Marly Teles de Carvallho, PhD,4 Jesus Antonio de Carvalho Abreu, MSc,5
Diego Rodrigues Pessoa, MSc,6 and Emilia Angela Lo Schiavo Arisawa, PhD1
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Abstract

Background: Diabetic neuropathy (DN) is one of the major complications developed by individuals with
diabetes mellitus. DN is responsible for a high morbidity and mortality rate and impacts the public health and
medical assistance resources. Intradermic laser irradiation on blood (ILIB) consists of the application of light
beams on the radial arterial, providing anti-inflammatory and vasodilator effects, antiarrhythmic action, reduction
of glucose, and stabilization of the hormonal and immunological systems. These effects help to maintain the
physiological dynamics of the body.
Objective: The goal of this research was to evaluate the effects of ILIB to relieve pain and improve the quality
of life in DN patients. The sample comprised 30 diabetic volunteers with DN, randomly distributed into
3 groups: Control—conventional treatment; ILIB—100 mW, 660 – 10 nm, 30 applications in total, divided into
3 stages of 10 applications, 30 min each, daily, with a 20-day interval between each stage; SILIB—same
protocol described for ILIB, with the equipment switched off. Before and after the application of the therapeutic
protocols, all volunteers were evaluated by the following instruments: Medical Outcomes Study 36-Item Short-
Form Health Survey (SF-36), visual analog scale, Leeds Assessment of Neuropathic Symptoms and Signs
(LANSS), and PAIN DETECT scale. Collected data were statistically analyzed with a 95% confidence interval,
p < 0.05.
Results: The ILIB group presented significantly lower pain levels and a better quality of life compared with the
control and SILIB groups.
Conclusions: This study demonstrated that ILIB therapy was effective in reducing pain and improving quality
of life in patients with DN.

Keywords: diabetes mellitus, diabetic neuropathies, pain, photobiomodulation

Introduction DM is a serious public health problem that affects *14.3

T he liver is one of the most important organs in the
glucose metabolism and is closely related to the patho-
physiology of diabetes mellitus (DM).1 DM is characterized
by increased glucose levels (hyperglycemia) owing to the
secretion and/or action of insulin on the human organism.2,3
million people in Brazil. According to current estimates, by
2040, 23.2 million individuals will be diagnosed with DM.4
DM classification varies according to its etiology, which
is categorized into three major groups: type-1 DM [related
to the destruction of beta (b) pancreatic cells with absolute
insulin shortage and a trend toward ketoacidosis], type-2

1
Research and Development Institute (IP&D), Vale do Paraı́ba University-Univap, São José dos Campos, Brazil.
2
Laboratory of Sensory Motor Rehabilitation Engineering, Research and Development Institute (IP&D), Vale do Paraı́ba University-
Univap, São José dos Campos, Brazil.
3
HABILASER Chief Executive Officer, Lasertherapy Training Course, São José dos Campos, Brazil.
4
Laboratory of Dentistry and Applied Materials (LOMA), Institute of Research and Development (IP&D), Vale do Paraı́ba University-
Univap, São José dos Campos, Brazil.
5
Cardiovascular Surgery-UNIFESP/EPM, Piauı́ State University (UESPI), Teresina, Brazil.
6
Piauı́ Higher Education Association (AESPI), Estácio de Teresina College and Piauı́ College of Technology (FATEPI/FAESPI),
Teresina, Brazil.

138
 LASER IN PATIENTS WITH DIABETIC NEUROPATHY
DM (resulting in resistance to the production of insulin
levels and deficiency in its production by the body), and
gestational DM (which can be identified in the second an-
d/or third gestational trimester).5 According to Hazari et al.,6
individuals diagnosed with type-2 DM are more susceptible
to developing diabetic neuropathy (DN) since this condition
reaches the sensory, motor, and autonomic nerves, leading
to the progressive degeneration of nerve fibers, in addition
to vascular and musculoskeletal complications and progress
to ulceration, gangrene, and limb amputation.
Currently, in professional practice, several photo-
therapeutic resources have been used to promote the control
of edema, pain, and the repair process in individuals diag-
nosed with DN. Among the phototherapy resources, we
highlight photobiomodulation (PBM) per low-level laser,7,8
the light-emitting diode9 and, recently, transcutaneous irra-
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diation with a modified laser (ILIB).10–12 These techniques
have been widely studied to stimulate wound healing in
individuals diagnosed with DN.
ILIB is a form of modified laser irradiation performed on
the skin (topical), punctually applied on a region of the
radial artery, allowing effects to favor all physiological
dynamics of the organism; antibacterial, anti-inflammatory,
vasodilator effects, and stabilization of the hormonal and
immunological systems. Other additional effects are de-
tected, including the triggering of the antioxidant system
composed of enzymes. The main enzyme is the melatonin
enzyme, superoxide dismutase (SOD ZnCu), which results
in the blockade of prostaglandin production by cycloox-
ygenase on arachidonic acid, leading to the blockade of the
inflammatory process at the systemic level.10–12 The present
study aims to evaluate the effects of intradermic laser irra-
diation on blood (ILIB) in relieving pain and improving the
quality of life in patients with DN.
Materials and Methods
This is a clinical, controlled, randomized, prospective,
interventional, and qualitative/quantitative study. This re-
search was approved by the Ethics and Research Committee
(ERC) of the State University of Piauı́ (UESPI-CAAE:
70966117.5.0000.5209). All volunteers participating in the
research were informed and oriented about the objectives
and procedures to which they would be submitted. After full
acceptance, all volunteers signed the Informed Consent
Form (ICF), thus respecting the ethical and legal premises
proposed by Resolution No. 466/2012 of the National
Health Council (NHC). The study was conducted from
February 2018 to February 2019 in the Blue Ambulatory
section of the Hostipal Getúlio Vargas (HGV), located in the
city of Teresina-PI.
The following eligibility criteria were established for
selecting the participants: As inclusion criteria, the follow-
ing precepts were adopted: diagnosis of type II diabetes
uncontrolled, DN in the lower limbs (leg and feet), glycemic
values between 150 and 350 mg/dL, and between 45 and 60
years of age.13 Patients were excluded from the study if they
had unstable glycemic control and/or medical conditions
that would confound assessment of neuropathy such as
malignancy, active/untreated thyroid disease, peripheral
vascular diseases, vascular insufficiency (claudication, skin
discoloration, ulceration), significant renal or hepatic dis-
139
ease, pregnancy, alcohol or illicit drug abuse, and other
neurologic diseases.13
The sample consisted of 30 volunteers with DM, meeting
the eligibility criteria previously described for DN. The
participants were randomly assigned to three groups: con-
trol, simulated transcutaneous irradiation with a modified
laser (SILIB), and ILIB. The randomization process was
characterized by the use of a cardboard system that main-
tains the complete randomness of the assignment of volun-
teers in the studied groups. The process was conducted by
an angiologist (responsible for the physical examination and
reliable diagnosis of DN) and a nurse (responsible for in-
structions regarding the proposed therapies).
Volunteers in the control group received the conventional
treatment prescribed for treating DN, including tricyclic anti-
depressants (amitriptyline hydrochloride 300 mg, produced by
Neo Quı́mica, São Paulo, São Paulo-Brazil), each tablet con-
taining amitriptyline hydrochloride 25 mg, microcrystalline
cellulose, sodium starch glycolate, silicon dioxide, dibasic
calcium phosphate, FD&C No. 05 yellow lacquer dye, and
magnesium stearate; anticonvulsants (Gabapentin 300 mg,
manufactured by Ems.sigma Pharma LTDA, Hortolândia, São
Paulo-Brazil), each capsule containing gabapentin 300 mg,
povidone, and talc; and opioid drugs (tramadol hydrochloride
100 mg/mL, produced by Neo Quı́mica), each mL of the oral
solution containing tramadol hydrochloride 100 mg, glycerol,
propylene glycol, sodium saccharin, sodium cyclamate, poly-
sorbate 80, potassium sorbate, peppermint oil, and water, with
40 drops corresponding to 1 mL of the medicine.
SILIB group underwent a simulation of ILIB applications
associated with the conventional treatment previously de-
scribed. They were placed in a comfortable position, and
after local asepsis, a specific ILIB bracelet was placed in the
radial artery region of each volunteer (Fig. 1). Afterward,
the simulation protocol (device switched off) was applied
by using a therapeutic laser in the red electromagnetic
spectrum (100-mW power and 660 – 10 nm wavelength) on
the skin surface for 30 sessions divided into 3 steps with 10
applications of 30 min each for 10 sequential days. There
was a rest period of 20 days between steps, and the protocol
was repeated twice, as described in Table 1. The volunteers
in the ILIB group underwent active ILIB applications as-
sociated with the conventional treatment previously de-
scribed in Table 1.
Personal data and history related to DM and DN of all
participants were collected. The following instruments were
used to evaluate the efficacy of the clinical protocols pro-
posed in this study:
1. Visual Analog Scale (VAS): a useful and reliable tool
to evaluate the intensity and quantify the pain per-
ception. VAS is a numerical scale ranging from 0 to 10
that indicates the absence of pain (0) and the worst
possible pain (10). This tool enabled pain evaluation
from the perspective of the volunteer.14
2. The Leeds Assessment of Neuropathic Symptoms and
Signs (LANSS): an instrument composed of seven
questions used to collect the patient’s history, physical
examination information, and pain sensitivities and
specificities, as well as DN diagnosis.14
3. PAIN DETECT: an instrument that discloses informa-
tion highlighting the diversity of pain manifestations
 140 DA SILVA LEAL ET AL.

FIG. 1. Pen and bracelet

for application of ILIB (A).
Bracelet positioning region
and ILIB application tech-
nique (B). ILIB, intradermic
laser irradiation on blood.

and the complexity of the underlying biological mech- Results

anisms such as the presence of allodynia or hyper-
algesia. It is composed of seven questions that address
the quality of pain symptoms. Adequate evaluation of
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Anthropometric and clinical characteristics of patients
All 30 volunteers in the three studied groups (control,
SILIB, and ILIB) were diagnosed with type-II DM and

pain and paresthesia is fundamental in verifying the

efficacy of treatment protocols proposed in clinical suffered from DN. None of them had neoplasia or autoim-
practice as new therapeutic options for DN.15 mune diseases. Table 2 lists the results obtained for the
4. Medical Outcomes Study 36-Item Short-Form Health clinical and anthropometric evaluations of the individuals
Survey (SF-36): This instrument consists of 36 ques- participating in this study. The participants’ age range in the
tions covering the evaluation of 8 components: func- control group was 67.0 – 2.0 years, and the volunteers’ body
tional capacity (10 items), pain (2 items), general mass index (BMI) was 28.0 – 2.0 kg/m2. The glycemic in-
health status (5 items), physical aspects (4 items), vi- dexes were 226 – 16 mg/dL, and the duration of the disease
tality (4 items), social aspects (2 items), mental health was 12.0 – 1.0 years. In the placebo group, the age of par-
(5 items), and emotional aspects (3 items). The SF-36 ticipants was 59.0 – 1.0 years, BMI 28 – 1.0 kg/m2, glycemic
questionnaire aims at identifying the quality of life for index 225 – 17 mg/dL, and disease duration 11.0 – 1.0 years.
people with DN before and after the application of Finally, the ILIB group had the following characteristics:
treatment protocols to analyze the aspects most influ- age range 66 – 1.0 years, BMI 26.0 – 1.0 kg/m2, glycemic
enced by the disease and the patients’ degree of sat- index 238 – 15 mg/dL, and disease duration 2.0 years.
isfaction with life.16 In Table 3, all studied groups (100% of the volunteers) used
hypoglycemic medication. The volunteers in all studied
Data were analyzed with the aid of the GraphPad Prism groups also had systemic arterial hypertension as an associated
program, v. 5. A Kolmogorov–Smirnov normality test was disease. In the control group, 60% of the volunteers had active
used to analyze the sample data distribution, followed by lifestyle habits, and 40% were sedentary. In the SILIB group,
Wilcoxon’s nonparametric test for intragroup comparison 70% of the volunteers had active living habits, and 30% were
(before and after treatment). In the intergroup evaluation, sedentary. In the ILIB group, 50% of the volunteers presented
the Kruskal–Wallis test was performed with a Dunn’s post- active lifestyle habits, and 50% were sedentary.
test. A 5% ( p < 0.05) significance level was considered for
all tests. Evaluation of pain in patients with DN
The results were obtained after 30 days with the VAS
(Fig. 2A), LANNS (Fig. 2B), and by applying the PAIN
Table 1. Parameters of SILIB and ILIB
DETECT questionnaire (Fig. 2C). The degree of pain in the
Parameters SILIB and ILIB different patient groups of this study was evaluated, presenting
a statistically significant difference in pain reduction and relief
Wavelength (nm) 660 – 10 nm after ILIB applied by all used tools (VAS, LANNS, and PAIN
Operation mode Continuous wave DETECT). In turn, the comparison of results obtained be-
Average radiant power (mW) 100 tween the initial and final moments of the therapeutic proto-
Polarization Random cols in the SILIB and control groups did not disclose a
Aperture diameter (cm2) 0.06
statistically significant difference in pain relief.
Irradiated area (cm2) 0.003
Irradiance (W/cm2) 1.666 Table 2. Results of Quantitative Anthropometric
Radiant exposure ( J/cm2) 3.000 Data Analysis of Control, SILIB, and ILIB Groups
Exposure time per point (s) 1800
Radiant energy per session ( J) 180 Groups
Number of irradiated points 1
Application technique Transcutaneous contact Data Control SILIB ILIB
Number of sessions during 10 consecutive days, a,b
therapy repeated after 20 days, Age (years) 67 – 2 59 – 1 66 – 2
for a total of three cycles Body mass index 28 – 2 28 – 1 26 – 1
Blood glucose level (mg/dL) 226 – 16 225 – 17 238 – 15
Equipment Easy Laser (DMC, São Carlos, Brazil). Duration of disease (years) 12 – 1 11 – 1 16 – 2
ILIB; SILIB, simulated transcutaneous irradiation with a modi-
a b
fied laser. Intergroup analysis p < 0.05: vs. Control, vs. SILIB.
 LASER IN PATIENTS WITH DIABETIC NEUROPATHY 141

Table 3. Results of Qualitative Anthropometric Analysis of quality-of-life domains

Data Analysis (%) of Control, with SF-36 questionnaire
SILIB, and ILIB Groups
Table 4 lists the results of a comparison (intragroup and
Groups intergroup) between the values of the initial evaluation (pre-
therapy) and final evaluation (posttherapy) of the studied
Data Control SILIB ILIB groups (control, SILIB, and ILIB). The results of the control
Lifestyle habits (% active vs. % 60/40 70/30 50/50 group demonstrated that both in the intragroup and intergroup
sedentary) evaluations, none of the variables studied through the SF-36
Systemic arterial hypertension (%) 100 100 100 presented significant differences in the initial evaluation
Hypoglycemic medication 100 100 100 (pretherapy) vs. the final evaluation (posttherapy). In the
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FIG. 2. Results of pain analysis with the aid of

(A) VAS, (B) LANNS, and (C) PAIN DETECT
tools between control, SILIB, and ILIB groups.
Intragroup analysis (Wilcoxon test): *p < 0.05,
**p < 0.01, ***p < 0.001. Intergroup analysis
p < 0.05 (Kruskal–Wallis test with Dunn’s post-
test): a. vs. initial ILIB, b. vs. final ILIB, c. vs.
initial SILIB, d. vs. final SILIB. LANSS; SILIB,
simulated transcutaneous irradiation with a modi-
fied laser; VAS, visual analog scale.
 142 DA SILVA LEAL ET AL.

Table 4. Results of Quality-of-Life Analysis (SF-36), Classified by Domains, in Control, SILIB, and ILIB
Group at Initial (Pre-Therapy) and Final (Post-Therapy) Moment
SF-36 (mean – EP)
Control SILIB ILIB
Domains Initial Final % p Initial Final % p Initial Final % p
FC 45 – 6 44 – 4U -2.3 ns 49 – 4 54 – 6U 9.3 ns 40 – 8 75 – 6 47 0.006*
PAL 35 – 7 34 – 5U -2.9 ns 65 – 6U# 65 – 6U# 0.0 ns 37 – 8 68 – 8 45 0.005*
Pain 39 – 6 42 – 5U 7.1 ns 48 – 2U 55 – 2U 13 0.024* 32 – 3 81 – 2 60 0.006*
GHS 29 – 4 30 – 4U 3.3 ns 39 – 3 43 – 3U 9.3 ns 35 – 3 76 – 4 54 0.006*
VTL 40 – 3 39 – 4U -2.5 ns 43 – 3 40 – 4U -7.5 ns 40 – 3 74 – 6 46 0.006*
SA 43 – 8 43 – 8U 0.0 ns 50 – 4 50 – 4U 0.0 ns 62 – 6 81 – 7 23 0.005*
EAL 35 – 5 32 – 4U -9.3 ns 57 – 7 53 – 6 -7.5 ns 40 – 10 77 – 7 48 0.008*
MH 46 – 3U 46 – 3U -0.0 ns 53 – 3 53 – 3U 0.0 ns 57 – 3 84 – 4 32 0.006*
The representation of the statistical results was: intragroup analysis (initial vs. final) *when p < 0.05 and intergroup analysis, #when
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p < 0.05 vs. control, and Uwhen p < 0.05 vs. ILIB.
%: improvement *Intragroup analysis (initial vs. final): *p < 0.05. Intergroup analysis p < 0.05: #vs. control, Uvs. ILIB.
EAL, emotional aspects limitations; FC, functional capacity; GHS, general health status; MH, mental health; PAL, physical aspects
limitations; SA, social aspects; VTL, vitality.
SF-36, 36-Item Short-Form Health Survey.

SILIB group, the conclusions from the measured values in-
dicated that only the pain variable ( p = 0.024) presented sig-
nificant results between the initial and final evaluations of the
studied participants. The ILIB group presented significant
values for all variables obtained in the pretherapy (initial) and
posttherapy (final) evaluation, that is, functional capacity
( p = 0.006), limitations owing to physical aspects ( p = 0.005),
pain ( p = 0.006), general health status ( p = 0.006), vitality
( p = 0.006), social aspects ( p = 0.005), limitations by emo-
tional aspects ( p = 0.008), and mental health ( p = 0.006).
Discussion
This study evaluated the effectiveness of ILIB in pain
relief and improving the quality of life in patients with DN
through the application of the SF-36 questionnaire and the
VAS, LANNS, and PAIN DETECT scales. ILIB group
displayed significant values for all variables of the quality-
of-life questionnaire, whereas the other groups (Control and
SILIB) did not present significant differences.
The results showed that patients who underwent the ILIB
treatment protocol presented a decrease in pain symptom-
atology and improved quality of life. Thus, it is possible to
affirm that the analgesic effect in DN is directly related to
intravascular irradiation with a modified laser (ILIB).
It is noteworthy that pain is an impacting factor on the
quality of life in diabetic patients with DN. Therefore, it was
possible to notice that the volunteers in the ILIB group re-
ported at the end of the treatment a very great relief re-
garding their pain patterns, and that this analgesia impaired
the domains evaluated by the SF-36 quality-of-life survey.
Khoo et al.17 demonstrated that ILIB has excellent results
in a wide range of conditions, including hyperglycemia,
neuropathy, and wound healing in diabetic patients. PBM
using ILIB as a power source probably increased oxygena-
tion, resulting in decreased tissue hypoxia and improved
tissue metabolism. In addition, active nonspecific mecha-
nisms of anti-infectious immunity, increases complement
activity and plasma immunoglobulin levels (IgG, IgA, and
IgM), reduces C-reactive protein platelet aggregation, im-
proving peripheral circulation.18,19 These actions of ILIB
phototherapy may result in pain relief and improve several
other conditions in patients with DN, as detected by the
responses obtained in the various instruments applied, re-
sults not observed in groups C and SILIB.
The SF-36 quality-of-life questionnaire served as a pa-
rameter to evaluate several important aspects of the impact
of DN on the quality of life of the study participants. EVA,
LANNS, and PAIN DETECT scales were efficient in eval-
uating symptoms. All evaluation instruments used in our
study present results that show pain relief after ILIB, re-
ported by the volunteers with DN.
The red electromagnetic spectrum at 660 – 10 nm provi-
des anti-inflammatory effects when used with adequate do-
simetric parameters (energy and time of irradiation), as well
as stimulate tissue regeneration, making it possible to reduce
pain and improve the quality of life in patients with DN.
Derkacz et al.20 showed that PBM per ILIB at wavelengths
between 632 nm (helium/neon laser) and 650 nm (semicon-
ductor laser) attenuated the inflammatory process, whereas
wavelengths between 730 and 830 nm resulted in a more
effective improvement in tissue healing. The authors re-
ported that these effects of ILIB therapy decreased pain and
improved quality of life in patients undergoing angioplasty.
Our results are reinforced by those obtained by Gomes
and Schapochnik,21 who reported that the effects of PBM
with ILIB, irradiated at the red wavelength and applied to
the radial artery, produce a systemic effect. In addition, the
irradiation at infrared region stimulated the tropism of the
muscular tissue. PBM associated with physical exercise
favors the strengthening of the muscles and the defense
process of the organism against fungi and bacteria, provid-
ing more effective healing, and improving quality of life of
patients with DN.
According to Luo et al.,22 the action mechanisms of PBM
by ILIB may be associated since light absorption by the
radial artery may favor a systemic effect owing to metabolic
changes, not just at the irradiation site but also in more
distant areas. ILIB release substances into the bloodstream,
inducing vasodilation and blood flow increase. This class of
 LASER IN PATIENTS WITH DIABETIC NEUROPATHY
PBM provides a metabolic increase and improves the syn-
thesis of the main physiological regulatory protein of the
oxidative system, the SOD. In addition, this protein has the
purpose of inhibiting the action of reactive oxygen species,
leading to cellular protection against mutations. SOD also
interferes with the arachidonic acid cascade, with anti-
inflammatory effects, and increases prostacyclin production,
improving blood flow with consequent reduction of vascular
problems.23,24
The analysis of the data obtained before and after the
application of the studied protocols allows us to affirm that
ILIB presented favorable results in the treatment of DN.8 In
addition, ILIB is noninvasive, has no side effects and pro-
duces positive effects on local metabolism,22 micro and
macro circulation,23 as well as enhancing the immune sys-
tem,22 making it a relevant therapeutic option. Improving
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the tissue repair process in patients with DM is extremely
important to reduce the incidence of neuropathic pain (NP),
and the pain resulting from this situation, improving their
quality of life.12 The promising results obtained in the
present study stimulate new clinical research, with the same
methodological approach, to broaden the knowledge about
the systemic effects derived from ILIB. The present work
represents a first step for understanding the systemic effects
determined by transcutaneous irradiation of the radial artery
with ILIB in patients with DN.
Conclusions
The results of this study demonstrated that the utilization
of PBM per ILIB, when used in the red electromagnetic
spectrum, improved the quality of life of patients diagnosed
with DN. The therapeutic protocol using ILIB was able to
promote systemic effects in volunteers, confirming its main
effects such as cellular activation, the antioxidant effect,
anti-inflammatory action, and increased blood circulation.
This results in the prevention of DN in DM patients, im-
proving the quality of life of these patients. Therefore, we
recommend new clinical, controlled, and randomized stud-
ies using variables such as surface electromyography, sleep
quality, psychological aspects (anxiety, stress, and depres-
sion), and muscular strength to conduct new studies of PBM
per ILIB.
Acknowledgments
The authors thank Fábio Barros Brito for analyzing data.
Compliance with Ethical Standards
Ethics approval
All procedures carried out in the studies involving human
participants were in accordance with the ethical standards of
the institutional research committee of the State University
of Piauı́-UESPI (UESPI/CAAE No. 70966117.5.0000.5209)
and with the 1964 Declaration of Helsinki and its subse-
quent alterations or standards.
Informed consent
Informed consent was obtained from all individual par-
ticipants included in the study.
143
Author Disclosure Statement
No competing financial interests exist.
Funding Information
There was no funding provided for this article.
References
1. Kummer S, Klee D, Kircheis G, et al. Screening for non-
alcoholic fatty liver disease in children and adolescents
with type 1 diabetes mellitus: a cross-sectional analysis.
Eur J Pediatr 2017;176:529–536.
2. Salazar JJ, Ennis WJ, Koh TJ. Diabetes medications: im-
pact on inflammation and wound healing. J Diabetes
Complications 2016;30:746–752.
3. Mostafavinia A, Amini A, Ghorishi SK, Pouriran R, Bayat
M. The effects of dosage and the routes of administrations
of streptozotocin and alloxan on induction rate of type1
diabetes mellitus and mortality rate in rats. Lab Anim Res
2016;32:160–165.
4. Lima CLJ, Ferreira TMC, Oliveira PS, Ferreira JDL, Silva
EC, Costa MML. Characterization of users at risk of de-
veloping diabetes: a cross-sectional study. Rev Bras En-
ferm 2018;71(Suppl 1):475–482.
5. Punthakee Z, Goldenberg R, Katz P. Diabetes Canada 2018
clinical practice guidelines for the prevention and man-
agement of diabetes in Canada: definition, classification
and diagnosis of diabetes, prediabetes and metabolic syn-
drome. Can J Diabetes 2018;42(Suppl 1):S10–S15.
6. Hazari A, Maiya AG, Shivashankara KN, et al. Kinetics
and kinematics of diabetic foot in type 2 diabetes mellitus
with and without peripheral neuropathy: a systematic re-
view and meta-analysis. Springerplus 2016;5:1819.
7. Gomes CA, Leal-Junior EC, Biasotto-Gonzalez DA, et al.
Efficacy of pre-exercise low-level laser therapy on iso-
kinetic muscle performance in individuals with type 2 di-
abetes mellitus: study protocol for a randomized controlled
trial. Trials 2014;15:116.
8. Khamseh ME, Kazemikho N, Aghili R, et al. Diabetic
distal symmetric polyneuropathy: effect of low-intensity
laser therapy. Lasers Med Sci 2011;26:831–835.
9. de Oliveira Francisco C, Beltrame T, Ferraresi C, et al.
Evaluation of acute effect of light-emitting diode (LED)
phototherapy on muscle deoxygenation and pulmonary
oxygen uptake kinetics in patients with diabetes mellitus:
study protocol for a randomized controlled trial. Trials
2015;16:572.
10. KazemiKhoo N, Iravani A, Arjmand M, et al.
A metabolomic study on the effect of intravascular laser
blood irradiation on type 2 diabetic patients. Lasers Med
Sci 2013;28:1527–1532.
11. Kazemikhoo N, Rahbar MR, Akrami SM. Low-level laser
therapy along with intravascular laser in deep pressure ul-
cer resistant to conventional therapies. J Skin Stem Cell
2015;2:e30686.
12. Kazemikhoo N, Ansari F. Blue or red: which intravascular
laser light has more effects in diabetic patients? Lasers Med
Sci 2015;30:363–366.
13. Yamany AA, Sayed HM. Effect of low level laser therapy
on neurovascular function of diabetic peripheral neuropa-
thy. J Adv Res 2012;3:21.
14. Malik TA, Itani HES, Gandoura NA. The Neuropathic Pain
Scale and its reliability and validity for diabetic neuropa-
thy. Diabetic Foot 2015;1:13.
 144
15. Cappelleri JC, Bienen EJ, Koduru V, Sadosky A. Mea-
surement properties of painDETECT by average pain se-
verity. Clinicoecon Outcomes Res 2014;6:497–504.
16. Costa DR, Costa DR, Pessoa DR, Masulo LJ, Arisawa EALS,
Nicolau RA. Effect of LED therapy on temporomandibular
disorder: a case study. Sci Med 2017;27:ID25872.
17. Khoo NK, Shokrgozar MA, Kashani IR, et al. In vitro
therapeutic effects of low level laser at mRNA level on the
release of skin growth factors from fibroblasts in diabetic
mice. Avicenna J Med Biotechnol 2014;6:113–118.
18. Isner JM, Lucas AR, Fields CD. Laser therapy in the
treatment of cardiovascular disease. Br J Hosp Med 1988;
40:172–178.
19. Huang SF, Tsai YA, Wu SB, Wei YH, Tsai PY, Chuang
TY. Effects of intravascular laser irradiation of blood in
mitochondria dysfunction and oxidative stress in adults
with chronic spinal cord injury. Photomed Laser Surg 2012;
Downloaded by University of Rochester package NERL from www.liebertpub.com at 03/22/20. For personal use only.
30:579–586.
20. Derkacz A, Protasiewicz M, Pore˛ba R, Doroszko A, An-
drzejak R. Effect of the intravascular low energy laser il-
lumination during percutaneous coronary intervention on
the inflammatory process in vascular wall. Lasers Med Sci
2013;28:763–768.
21. Gomes CF, Schapochnik A. The therapeutic use of low
intensity laser (LLLT) in some diseases and its relation to
the performance in speech therapy. Distúrbios da Comu-
nicação 2017;29:570–578.
DA SILVA LEAL ET AL.
22. Luo L, Sun Z, Zhang L, Li X, Dong Y, Liu TC. Effects of
low-level laser therapy on ROS homeostasis and expression
of IGF-1 and TGF-beta1 in skeletal muscle during the re-
pair process. Lasers Med Sci 2013;28:725–734.
23. Gasparyan LV, Levon V, Brill G, Makela AM. Influence of
low level laser radiation on migration of stem cells. Laser
Florence 2004: A Window on the Laser Medicine World.
International Society for Optics and Photonics. 2005;5968:
58–63.
24. Mittermayr R, Osipov A, Piskernik C, et al. Blue laser light
increases perfusion of a skin flap via release of nitric oxide
from hemoglobin. Mol Med 2007;13:22–29.
Address correspondence to:
Milena Valdinéia da Silva, DDS, PhD
Research and Development Institute (IP&D)
Vale do Paraı́ba University-Univap
Avenida Shishima Hifumi, 2911
Sao Jose dos Campos 12244-000
Brazil
E-mail: milenaleal@bol.com.br
Received: June 22, 2019.
Accepted after revision: October 4, 2019.
Published online: February 28, 2020.