Injection of Subcutaneous Glucose 10% in Small Shots is Effective in the Treatment of Diabetic Neuropathic Pain

Objectives: The aim of this study is to show that if subcutaneous glucose 10% 0.5 ml injection around inflamed nerves can relieve diabetic neuropathic pain in comparison to control. Design: Observational cohort prospective study 2 months trial. Materials and Methods: Observational cohort prospective study with the following of 100 patients of type 1 and type 2 diabetes mellitus in 2 groups each group 50 patients, each group 30 males, and 20 females,35 patients with type 2 diabetes and 15 patients type 1 diabetes all have diabetic peripheral neuropathy, the second group is considered as control. Conclusion: Diabetic neuropathy is considered as a great problem affecting most of the diabetic patients with moderate to severe pain. Subcutaneous glucose injection around inflamed nerves is considered as a new option for the treatment of neuropathic pain and muscle pain.


INTRODUCTION
Diabetes mellitus is considered as the biggest global burden in the last years. With increasing prevalence due to modern lifestyles with no exercise, reaching more than 400 million cases all over the world, which put a great impact on productivity? The increase in diabetes occurrence is related to increased age, in which more than 20% of peoples over 60 years have diabetes [1].
Diabetes mellitus is one of the most important causes of peripheral neuropathy at this time, which is mostly in the form of distal symmetrical polyneuropathy in more than 90% of patients which may be presented as small fiber damage with a burning sensation or with large fiber damage with numbness [2].
Distal symmetrical polyneuropathy begins distally from the toes and progress proximally in a slow fashion to include the feet then the legs. The most frequent complication is the foot infections, foot ulcers and there is a risk of leg amputation in diabetic patients with diabetic neuropathy [3]. Diabetic neuropathy pain is burning and may lead to an electric Prolotherapy is considered as a new option for the treatment of neuropathic pain and muscle pain. Glucose as an irritant material may be injected in the site of pain and in the tendons [17]. How glucose control neuropathic pain is a marvelous thing in which glucose hyperpolarize nerves by acting on potassium channels, and so diminishing nociceptive pain fibers transport [18]. Glucose solution is thought to give rise to inflammatory action giving rise to chemical inflammatory mediators including ILGF, EGF, PDGF, TGF-beta and CTGF resulting in stimulation of the healing process [19].
One of the mechanisms proposed to explain the pain-relieving effect of hyperosmolar glucose is blocking vanilloid type 1 receptor permitting the entrance of Ca2+ and Na+. Entrance of sodium result in action potential and nociception calcium entrance leads to the liberation of Journal of Pharmacological Research and Developments e-ISSN: 2582-0117 Volume 2, Issue 1 substance P and calcitonin gene-related peptide [20], and so preventing entrance of sodium and potassium could decrease neuropathic pain [22].

MATERIALS AND METHODS
Observational cohort prospective study with the following of 100 patients of type 1 and type 2 diabetes mellitus in 2 groups each group 50 patients, each group 30 males, and 20 females,35 patients with type 2 diabetes and 15 patients type 1 diabetes all have diabetic peripheral neuropathy, the second group is considered as control. The ages of all patients are between 20 and 50 years.
The first group was on subcutaneous glucose 0.5 ml per site around subcutaneous nerves in the foot region both on palm and sole, which is repeated every 2 weeks for 2 months.
The aim of the study is to show if subcutaneous glucose 10% has a painrelieving effect on peripheral diabetic neuropathy pain.
Pain severity was evaluated by using the Visual Analogue Scale (VAS) which is a numerical rating scales, with a straight horizontal line of 100 mm. which is directed from the left with severe pain to the right with no pain. 1-3 = mild pain, 4-6 = moderate pain, 7-10 = severe pain.
The evaluation of neuropathy was done by using the Michigan Neuropathy Screening Instrument (MNSI) after translation to the Arabic language, which consists a 15 selfadministered questionnaires and examination lower extremities which comprise inspection and examination of vibratory senses and ankle reflexes. A score which is more than 7 was suggested to be abnormal.

RESULTS
Patients group was compared to the control group before and 2 months after treatment of subcutaneous 10% glucose. Analysis of that was done using GraphPad. Paired 't' test was done to analyze pre-post changes within the group and between the 2 groups Journal of Pharmacological Research and Developments e-ISSN: 2582-0117 Volume 2, Issue 1         The results show that subcutaneous 10% glucose shots showed significant reduction in Pain using VAS scale with mean of 7.520 to mean of 0.5000 with p-value less than 0.0001 in the group who were on sc glucose as seen in Table 5 and Fig. 3, and in comparison to the control group as in Table 1, 3 and Fig. 1.
In MNSI score with a mean of 7.020 to mean of 2.540 significant p-value less than 0.0001 as seen in Table 4 and Fig. 4 in patients who were on sc glucose, and in comparison to the control group as seen in Table 2 and 4 and Fig. 2.

DISCUSSION
Diabetic neuropathy is prevalent in most type 1 and type 2 patients, in which presented mainly by pain, which is caused mainly by chronic hyperglycemia. Treatment is by controlling hyperglycemia and drugs decreasing pain [22].
Diabetic neuropathy results due to nerve injury and tissue damage. Pain and temperature nerve fibers are the most affected [23].
Also, microcirculation is affected leading to muscle atrophy, foot infection, and foot ulcers [24]. Diabetic neuropathic pain is mainly localized to the foot [25].
Available treatment for diabetic neuropathy is only for relieve of symptoms and don't have any effect on the progress of the disease. These drugs may lead to many side effects which cannot be afforded by a large number of patients [26].
There are also trials for using other managements for diabetic neuropathy like a cold laser, acupuncture [27], transcutaneous electrical nerve stimulation (TENS). All of these procedures for pain relieve is still not guaranteed as effective [28].
Hypertonic glucose injection is used for pain relieve in various chronic musculoskeletal conditions. Usually, a small volume of hypertonic glucose (0.5 ml) is injected in painful sites as around inflamed nerves [29].
In this trial glucose, 10% was injected in painful sites in the foot in the palm and sole regions.
My finding in this study shows that subcutaneous glucose 10%, when injected by 0.5 ml in various painful sites in the foot, led to relieve of neuropathic pain in diabetic neuropathy and also led to improvement in nerve functions.
The restriction of my study is the few patients sample size. While the inclusion of a small number of patient's limits and restricts the extrapolation of our findings to the general population.

CONCLUSION
As diabetic neuropathy is considered as a great problem affecting most of the diabetic patients with moderate to severe pain, subcutaneous glucose injection around inflamed nerves is considered as a new option for the treatment of neuropathic pain and muscle pain. The data used to support the findings of this study are included in the article.

Conflicts of Interest
There is no conflict of interest to declare. Funding No funding Acknowledgement Contributions "Mahmoud Younis wrote the manuscript and researched data, reviewed/edited the manuscript, discussion and reviewed/edited the manuscript." "Dr. Mahmoud Younis is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis."