The Hypoglycemic Effect of Intravenous Laser Therapy in Diabetic Mellitus Type 2 Patients;
A Systematic Review and Meta-analyses
Kazemikhoo N1, 2,,Ansari F2* and Nilforoushzadeh2
1Skin Diseases and Leshmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
Received Date: September 28, 2015, Accepted Date: November 10, 2015, Published Date: November 13, 2015
Citation: Kazemikhoo N,Ansari F,Nilforoushzadeh,The Hypoglycemic Effect of Intravenous Laser Therapy in Diabetic Mellitus Type 2 Patients; A Systematic Review and Meta-analyses.Med Clin Rev. 2015, 1:7. doi: 10.21767/2471-299X.1000007
Copyright: © 2015 Kazemikhoo N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Objectives: Intravenous Laser Blood Irradiation (ILBI) is applied in some countries for the treatment of different diseases including diabetes mellitus. But there is not any systematic review available in this field. The aim of this study is to review the articles on the effects of ILIB in diabetic type 2 patients systematically. Material and Methods: PubMed, SciELO, Science Direct and Google Scholar databases were searched for primary articles: The literature search was restricted to studies published in English and from the unrestricted past till April 2015. The keywords used were "Intravascular laser", "Intravenous laser", "low level laser", "low intensity laser", "phototherapy", "cold laser" combined with "fasting blood glucose", "blood sugar" and "blood glucose". Results: Seven potentially suitable articles were found and among them four articles met all inclusion criteria. All these 4 articles were included in the final metaanalysis. Comparing before and after laser therapy, showed a significant decrease in glucose level (mean difference =14.445, 95% CI: −1.12 to 30.031 P=0.007). There was not any significant heterogeneity between trials (P=0.158, I2=42.3%). Conclusion: ILIB is a safe and effective therapeutic modality for decreasing blood sugar level in diabetic type 2 patient.
Keywords Intravenous laser; FBG; Systematic review
During past 40 years, Low-level Laser Therapy (LLLT) has been broadly used in medical fields. Recently, there has been an increase in the clinical applications of low-level laser irradiation in various therapeutic fields. One of the most important functional aspects of laser therapy is photobiostimulatory effects of low-level lasers on various biological systems that is based on the effects of low intensity lasers, often described as lasers with less than 500 mW average power [1-4]. One of the Methods for irradiation of laser is Intravenous or (ILBI) with red, UV, and blue light, which is widely applied in the treatment of different pathologies. Blood irradiation therapy can be administered through a catheter in a vein, usually a vein in the forearm . The medical effects are mainly systemic healing mechanisms including analgesic, biostimulative, immunocorrective, antibacterial, anti-allergic, antitoxic, vasodilative, antiarrhythmic, antihy-poxic, spasmolytic, anti-inflammatory, and other properties . It expands the arteriovenous oxygen difference that affirms the liquidation of a tissue hypoxia and enrichment of oxygenation which is a sign of tissue metabolism normalization and improves oxidation of energycarrying molecules like glucose, pyruvate, and other substances. Laser irradiation activates ATP synthesis and energy formation in cells . ILIB reduces glucose, cholesterol, low-density, and very low density lipoproteins (VLDL) and alleviates immune and hormonal system status. As ILBI has systematic effects, it can be a proper therapeutic modality in complex diseases like diabetes mellitus. Diabetes is a pathological metabolic state caused by insufficient transport and breakdown of glucose. It reveals low serum insulin to glucagon ratio and high levels of fatty acids. The liver produces glucose while other tissues use ketones and fatty acids instead of glucose .
As there is not any systematic review available in the field of the effects of ILIB in diabetic type 2 patients, we designed this study to review these articles systematically.
Materials and Methods
The following databases were searched for primary articles: PubMed, SciELO, Science Direct and Google Scholar. The literature search was restricted to studies published in English and from the unrestricted past till April 2015. The keywords used were "Intravascular laser", "Intravenous laser", "low level laser", "low intensity laser", "phototherapy", "cold laser" combined with "fasting blood glucose", "blood sugar" and "blood glucose".
Studies were eligible for inclusion if they fulfilled the following criteria: (i) enrolled participants diagnosed with type 2 diabetes; (ii) Intra venous laser irradiation was applied; (iii) The blood sugar of patients before and after laser irradiation has been measured.
Studies were excluded if they (i) included participants diagnosed with pre-diabetes, gestational diabetes, or type 1 diabetes; (ii) reported only categorical data of outcomes; or were posters or just abstracts. Studies that gave insufficient information regarding the laser interventions were also excluded if the related information could not be obtained from the corresponding authors.
Initial screen was based on titles or abstracts of retrieved publications; if they provided inadequate information with regard to inclusion or exclusion criteria, full-text articles were retrieved and evaluated. For each study, data regarding study sources (including author and publication year), characteristics of study population (including sample size, baseline mean age, sex [proportion of females] and duration of diabetes), characteristics of laser therapy (including frequency, intensity and wave length of laser applied), mean and standard deviation or standard error of mean of fasting blood sugar (FBS) before and after laser therapy and adherence and dropout rates, were extracted.
Two authors performed the literature selection, data collection, and quality assessment of studies.
In Kazemikhoo’s  study, 2015 the results of blue and red laser irradiation and all the repetitions have been combined. The Change from baseline after laser irradiation was entered in the meta-analysis and SD of mean difference was calculated using SD of glucose level before and after laser therapy and r equals 0.93.
r=Pearson correlation coefficient.
SDB=Standard deviation of glucose level before laser therapy.
SDB= Standard deviation of glucose level after laser therapy.
SDC= Standard deviation of glucose level changes.
The heterogeneity among studies was assessed using Q test, with a P value of <10 being considered of statistical significance.
Publication bias in the meta-analyses was detected and assessed by the Begg's test and Egger's test. Statistical analyses were performed using STATA Software (Version 12.0, College Station, Texas, USA).
The initial search identified 7 potentially suitable articles and among them 4 articles met all inclusion criteria. All these 4 articles were included in the final meta-analysis.
The detailed characteristics of these trials are summarized in Table 1. Of these 4 trials, a total of 70 participants were included, with sample sizes ranging from 9 to 27 in individual trials.
Number of subjects
Mean age (Years)
Blood sugar before mg/dl (Mean ± SD)
Blood sugar after mg/dl (Mean ± SD)
R. Chen, 2000 (Chen, Chen, Xie, Chen, & Zhang, 2000)
He-Ne laser extravacular irradiation therapy instrument, , O—4Omw, 632.8nm, 60 min
T.V. Kovalyova, 2002 (Kovalyava, 2002)
ILBI intravenously2 mW,l =0,63 mm 405-nm 15-30 min
N. KazemiKhoo, 2013 (N Kazemi Khoo et al., 2013)
ILBI intravenously1.5 mW, continuous, 405-nm 30 min
N. KazemiKhoo, 2015 (KazemiKhoo & Ansari, 2015)
ILBI intravenously1.5 mW, continuous, 405-nm and 630 nm 20-30min-one day blue one day red laser therapy
Table 1 Characteristics of included trials.
All the participants were diabetic type 2 with the base line mean glucose level ranging from 190 mg/dl to 259 mg/dl.
Compared with the before laser therapy, the pooled estimate showed a significant decrease in glucose level (Mean difference =14.445, 95% CI: −1.12 to 30.03, p=0.007; Figure 1). There was not any significant heterogeneity between trials (P=0.158, I2=42.3%).
Figure 1: Forest plot of trials examining LLLT effects on glucose level in type 2 diabetes patients. ES, mean difference; CI, confidence interval Summary estimates were analyzed with a random-effects model.
There was no significant publication bias as evidenced by the Begg's test and Egger's test (all P>05).
The result of this meta-analysis suggests that Intravenous laser therapy decreases blood glucose level in diabetic type 2 patients significantly. Immediately after ILIB blood glucose decreases 14 mgr/dlit. It seems that laser irradiation may have an effect on arginine and increase nitric oxide (NO) production. Arginine affects on the release of hormone like glucagon, insulin, prolactin, adrenal catecholamins and growth hormone . It decreases tissue hypoxia, stimulates oxygenation and normalizes tissue metabolism . Ramadawon concluded that even in advanced cases of diabetes mellitus, laser therapy could restore the pancreas function and normalize the blood glucose level. They concluded that laser irradiation could stimulate and regenerate pancreatic tissues, including the Langerhans β-cells, even in advanced disease states .Tiedan et al reported that ATPase was significantly lower in diabetic patients than that in control subjects, and laser irradiation significantly activated Na+/K+- ATPase, Ca2+,Mg2+-ATPase. They suggested that intravascular laser might be a new complex therapeutics for diabetes .
However, it shows inadequate evidence regarding the effects of other factors related to health of diabetic people. Numerous studies showed the positive effect of laser therapy on diabetic complications [13-17]. Our previous studies showed that laser irradiation may be effective in neuropathy and wound healing in these patients [18-20].It could be recommended to include these factors for future systematic reviews.
Since results from this meta-regression find intravenous laser therapy as an effective way to decrease blood sugar level in diabetic patients it could be suggested to prescribe this kind of therapy for patients with type 2 diabetes along with other classic methods such as diet, weight control, medications and exercise to gain benefits on glycemic control [21,22].
To the time being, this is the first analysis that systematically assesses the hypoglycemic effect of intravenous laser therapy, in patients with type 2 diabetes. This study analyses the quantity of therapeutic effects of this method including Mean, SD and SE. We included trials with before-after study designs. Even though it is difficult to assess causal association in this kind of trials, they are the most feasible way to measure medical intervention effects. Due to small numbers of trials in this field it was the only way to include more trials and to improve external validity of the meta-analysis.
It is recommended that future RCTs with proper control groups and appropriate description of adequate information should be conducted. Despite no significant publication bias was detected by the Begg’s test and Egger’s test, the risk of publication bias still cannot be fully ruled out due to the language restriction to English, the selection of only published papers, as well as the potentially underpowered statistical tests.
In conclusion, the meta-analysis shows that Intravenous laser therapy is associated with a decreased blood sugar level among patients with type 2 diabetes. As the selected studies evaluate the effects of intravenous laser for a short period of time, it seems more studies are needed to assess the long term effects. Future RCTs with head-to-head designs comparing intravenous laser therapy versus hyperglycemia control drugs, and with extended length of interventions (6 months) and with assessing more health related outcomes, are required to strengthen the findings in this meta-analysis.
We dedicate here our acknowledgments to Dr.Mohammadreza Rahbar for English Edition of the manuscript.
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Photomedicine and Laser Surgery, Volume 31, Number 7, 2013
The Effects of Low-Level Laser Therapy on Palatal Mucoperiosteal Wound Healing and Oxidative Stress Status in Experimental Diabetic Rats
Ela Tules Firat, PhD,1 Ahmet DagË� , PhD,1 Ahmet GuÂ¨nay, PhD,1 Beyza Kaya, PhD,2 Mehmet _Irfan Karadede, PhD,3
Berna ErsoÂ¨z Kanay, PhD,4 Aydin Ketani, PhD,5 Osman EvliyaogË� lu, MD,6 and Ersin Uysal, PhD7
Objective: The biostimulation effects of low-level laser therapy (LLLT) have recently been demonstrated. In this study, we aimed to investigate the effects of LLLT on palatal mucoperiostal wound healing and oxidative stress status in experimental diabetic rats.
Methods: Forty-two male Wistar rats that weighed 250â€�300 g were used in this study. Experimental diabetes was induced in all of the rats using streptozotocin. A standardized full thickness wound was made in the mucoperiosteum of the hard palates of the rats using a 3mm biopsy punch. The rats were divided into groups: 1 (control group, non- irradiated), and 2 (experimental group, irradiated). Treatment using a GaAlAs laser at a wavelength of 940nm and at dose of 10 J/cm2 began after surgery, and was repeated on the 2nd, 4th, and 6th days post-surgery. Seven animals from each group were killed on the 7th, 14th, and 21st day after surgery. Biopsies were performed for the histological analysis and blood samples were collected by cardiac puncture for biochemical analysis.
Results: The histopathological findings revealed reduced numbers of inflammatory cells, and increased mitotic activity of fibroblasts, collagen synthesis, and vascularization in rats in group 2. The total oxidative status was significantly decreased in the laser-treated group on the 21st day.
Conclusion: LLLT elicits a positive healing effect on palatal mucoperiostal wounds, and modulates the oxidative status in experimental diabetic rats.
Lasers Surg. Med. 45:240â€�245, 2013.
Testing Infrared Laser Phototherapy (810 nm) to Ameliorate Diabetes: Irradiation on Body Parts of Diabetic Mice
Philip V. Peplow, PhD and G. David Baxter, DPhil, Department of Anatomy, University of Otago, Dunedin 9010, New Zealand
Centre for Physiotherapy Research, School of Physiotherapy, University of Otago, Dunedin 9010, New Zealand
Background and Objective: Irradiation of left flank of genetic diabetic mice with 660 nm wavelength laser, 100 mW, 20 seconds/day for 7 days did not significantly alter blood plasma glucose compared to nonirradiated controls. Infrared light would provide for a greater amount of photoenergy penetrating the skin and muscle. Genetic diabetic mice were irradiated with 810 nm wavelength laser to test for antidiabetic effect.
Methods: Sixty-five diabetic mice were used. Body weight and water intake of mice were measured daily for 7 days prior to start of treatment (Day 0). Mice were irradiated with 810 nm wavelength laser, 50 mW, 40 seconds/day, 7 days on left flank (n Â¼ 11), mid-upper abdomen (n Â¼ 14), or left inguinal region (n Â¼ 14); some mice were not irradiated (control, n Â¼ 26). Body weight and water intake of mice were measured to Day 7. On Day 7, mice were fasted for 4 hours, anesthetized with sodium pentobarbitone (s.c.) and blood collected by cardiac puncture into EDTA-treated tubes. Blood plasma was assayed for glucose and fructosamine. Blood was collected and assayed from nonirradiated nondiabetic mice (n Â¼ 12).
Results: On Day 7 body weight was significantly lower and water intake significantly higher compared to Day 0 for diabetic mice irradiated on left flank (40.7 0.5 vs. 42.2 0.4 g, 28.2 1.5 vs. 23.4 1.5 g, respectively); there was no significant change for diabetic mice irradiated on mid-upper abdomen or left inguinal region and also for nonirradiated diabetic mice. On Day 7 blood plasma glucose levels for irradiated diabetic mice were not significantly different to nonirradiated diabetic mice. Blood plasma fructosamine level of diabetic mice irradiated on left inguinal region was significantly lower than for nonirradiated diabetic mice (312 6 vs. 377 15 mmol/L); for diabetic mice irradiated on left flank or mid-upper abdomen (362 22, 357 19 mmol/L) it was not significantly different to nonirradiated diabetic mice.
Conclusion: Irradiation of left inguinal region in diabetic mice with 810 nm laser has potential to ameliorate diabetes as shown by decreased blood plasma fructosamine.