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August 12, 2019

Diabetes Treatments and the Role of Electrotherapy | NuroKor Evidence

Dr Luigi Vorluni PhD Physiology
Head of Science & Physiology at NuroKor BioElectronics

The objectives of this paper are to review the pathophysiology of diabetes and the social and economic cost, as well as the current screening, the treatment practice and the role of electrotherapy. Despite the enormous investment and relevant guidelines, diabetes prevalence is increasing at alarming rate worldwide. If unaddressed, it is set to continue deteriorating exponentially, and consequently the public health, medical and economic burden of diabetes also will increase extremely fast.

Electrotherapy is an approach that utilises electrical impulses, generated by specifically designed devices and delivered through electrodes placed on the skin. There is a large body of scientific evidence suggesting that electrotherapy represents an effective tool to treat a number of conditions, including diabetes. Also, electrotherapy has numerous other advantages, as this approach is non-invasive, non-pharmacological, non-toxic, non-addictive, safe, easy to administer and cost effective. Despite these qualities and advantages, electrotherapy remains underutilised. The evidence suggests that if electrotherapy is utilised optimally, it has an enormous potential to make diabetes treatment both more clinically and cost effective. Therefore, it is highly desirable to incorporate electrotherapy within the diabetes standard care routine.  

Pathophysiology of Diabetes

Diabetes is a metabolic disorder characterised by impaired ability to metabolise carbohydrates, resulting from an irregularity in insulin secretions, insulin actions or both. Absence of insulin secretion or reduced insulin effect, in turn leads to persistent abnormally high blood sugar and glucose intolerance. Diabetes is categorised into three main types. Type 1, also known as insulin-dependent diabetes, type 2 diabetes and gestational diabetes. Type 1 diabetes usually develops during childhood, and represents an autoimmune disease, where the beta cells in the pancreas are damaged by the body's own immune system, resulting in severely deficient insulin production. Gestational diabetes occurs during pregnancy, and usually disappears after giving birth. Type 2 diabetes usually develops during adulthood, and is by far the most common type of diabetes. 

Type 2 Diabetes

Glucose is a very important nutrient utilised by the body mainly to produce energy. Insulin is manufactured by the beta cells in the pancreas, and represents a key hormone in glucose metabolism. Insulin binds to specific receptors enabling glucose, present in the bloodstream, to enter the cells such as muscle, liver and fat cells, where it is used to produce energy. Type 2 diabetes is a condition in which glucose metabolism is impaired. In type 2 diabetes patients, the body’s inability to control and metabolise glucose results from increased insulin resistance, decreased insulin production or a combination of these factors. Insulin resistance involves a decrease in responsiveness of specific receptors, leading to increased blood glucose level. In turn this causes the pancreas to produce and release increasing amount of insulin, this is called hyperinsulinemia. Insulin production eventually reaches levels that are not sustainable, and consequently the beta cells in the pancreas start to deteriorate, leading to reduced insulin secretion. Because of insulin resistance and reduced insulin production, blood glucose increases to unhealthy level, this is known as hyperglycaemia and is typically observed in diabetic patients. 

Symptoms of Diabetes

The signs and symptoms of diabetes usually include:   

  • Strong thirst 
  • Irritability  
  • Frequent urination, especially at night 
  • Fatigue 
  • Weight loss (without trying)  
  • Blurred vision 
  • Sores, cuts or wounds that do not heal or take longer to heal 
  • Itching in the genitalia, or repeatedly getting thrush

The symptoms of type 2 diabetes generally develop gradually and initially may not seem serious. The severity of the symptoms vary, and in a number of cases the condition is not diagnosed until the manifestation of complications. Therefore, individuals experiencing diabetes symptoms should see their GP as early as possible to start the treatment and prevent complications. 

Causes of Diabetes and Possible Complications

The risk of developing type 2 diabetes is determined by an interplay of various factors, and include:

  • Unhealthy diet
  • Overweight and obesity, especially abdominal fat 
  • Physical inactivity  
  • Chronic stress affecting the hormonal balance 
  • Unhealthy lifestyle 
  • Genetic factors  
  • Smoking 

The above factors represent the main contributors, however, lack of physical activity combined with overweight and obesity are estimated to cause a large proportion of the global diabetes cases.  

If type 2 diabetes is left unchecked leads to a number of serious and life threatening complications, including:  

  • Atherosclerosis 
  • Cardiovascular diseases
  • Stroke
  • Peripheral neuropathy 
  • Kidney diseases 
  • Vision impairment and blindness
  • Ulcers and infections, especially in the lower extremities
  • Accelerated degenerative joint diseases 
  • Complications in pregnancy
  • Increased likelihood of sexual dysfunction

In addition to the complications described above, diabetes has been associated with increased rate of specific cancers, and increased rate of physical and cognitive disability, especially in the elderly population. 

Social and Economic Impact of Diabetes 

The incidence of diabetes is increasing dramatically worldwide, causing millions of cases of morbidity and premature death. Type 2 diabetes is usually diagnosed in people over the age of 40, with a peak in people between 60-70 years, but it appears that this condition can develop also in people of younger age. Diabetes affects enormously the life of patients and family, with suffering from complications and the resulting increased morbidity. It is estimated that from 2012 to 2030 the total number of people with diabetes worldwide will increase from 371.33 million to 551.87 million (about 180 million increase), which is twice the annual growth of the total global adult population. In the UK in 2013 were diagnosed 3.2 million people with diabetes, and it is estimated that five million will have diabetes by 2025.   

Despite the enormous amount of funds spent to treat type 2 diabetes, its incidence and complications are increasing dramatically. The management and treatment of type 2 diabetes require an efficient approach that combines the efforts of decision makers, health care systems, physicians and patients.

With life expectancy increasing and diabetes incidence augmenting, the treatment imposes a huge economic burden on the global health-care system and the wider global economy. Such burden comprises direct medical costs, and indirect costs resulting from productivity loss. A systematic review estimated that the direct annual cost of diabetes to the world is more than US$ 827 billion. According to the International Diabetes Federation (IDF) in a ten years period (2003 to 2013), the total global health-care spending on diabetes more than tripled, as a result of increased prevalence of diabetes and augmented diabetes spending per capita. It appears that this trend is set to continue. In the UK in 2012 the total cost (direct care cost and indirect cost) associated with diabetes was £23.7 billion and it is predicted to rise to £39.8 billion by 2035/6. 

Screening and Diagnosis Diabetes

Diabetes is a very serious medical condition, and when left unmonitored and untreated, blood glucose level can swing from dramatically low, called hypoglycaemia, to dangerously high, called hyperglycaemia. Hypoglycaemia can develop quickly, and the patients feel dizzy confused and uncoordinated, and often are pale and sweaty, with palpitations. If blood glucose level is not raised, symptoms could get worse and lead to coma. Whereas, hyperglycaemia can cause diabetic ketoacidosis, which is a life-threatening condition. Diabetic ketoacidosis signs and symptoms often develop quickly, sometimes within 24 hours. If left untreated, hyperglycaemia can become severe and lead to diabetic coma. Therefore, it is extremely important to maintain blood glucose to healthy level. Tests for screening and diagnosis of type 2 diabetes are available, and usually include glycated haemoglobin (HbA1c) test, which provides an indication the patient’s average blood sugar level for the past two to three months. Also, random blood sugar test, as well as fasting blood sugar test, where the blood sample is taken after an overnight fast. Oral glucose tolerance test is less commonly used than the others, except during pregnancy. For this test, the patient needs to fast overnight and then drink a sugary liquid at the physician's office. Blood sugar levels are tested regularly for the following two hours. After these tests are carried out, the physician normally takes in consideration the results along with typical diabetes symptoms in order to determine the presence of glucose intolerance or diabetes. In a number of cases diabetes patients have already signs of microvascular complications at the time of diagnosis, suggesting that they had the disease for about 4-7 years before clinical diagnosis.   

Table 1 Blood Glucose Tests and Reference Values

Diabetes Management and Treatments

The management and treatments of diabetes normally comprise pharmacological therapy and lifestyle changes. There are various medications prescribed to treat diabetes, and they are administered to achieve the following effects:

  • Decrease glucose production in the liver 
  • Improve insulin sensitivity
  • Stimulate insulin secretion
  • Prevent the kidneys from reabsorbing glucose into the blood stream  

The different types of medication help control diabetes, but they have various side effects. Besides, insulin usually is prescribed to type 1 diabetes patients, however, some patients with type 2 diabetes also need insulin administration. In addition to monitoring blood glucose and taking the medication, it is crucial that patients implement interventions that include increase the physical activity, and improve their diet and lifestyle. If these interventions are implemented correctly, they help control type 2 diabetes preventing complications, and also in some cases they put the condition in remission, leading to normal blood glucose level. However, the evidence suggests that type 2 diabetes is difficult to control, and remission is achieved in an extremely small number of cases. In fact, type 2 diabetes prevalence is increasing at alarming rate, and the resulting life-threatening complications are common.  

Treatment Challenges 

The uncertainty that pervades the realm of clinical care, demands a comprehensive and flexible method that can integrate the evidence relevant to the specific health condition and needs of patients, in order to help provide efficacious treatments. It should be considered that some conditions are inherently complex, making their diagnosis and treatment extremely challenging. Despite the enormous amount of funds spent to treat type 2 diabetes, its incidence and complications are increasing dramatically. The management and treatment of type 2 diabetes require an efficient approach that combines the efforts of decision makers, health care systems, physicians and patients. Integrative medicine utilises the best available evidence taking into account the whole person, including all aspects of lifestyle, and this approach is well suited to treat conditions such as type 2 diabetes. 

The Role of Electrotherapy in Treating Type 2 Diabetes 

Electrotherapy is an approach that utilises electrical impulses, generated by specifically designed devices and delivered through electrodes placed on the skin. Electrotherapy comprises different modalities, including peripheral nerve stimulation (PNS) also known as transcutaneous electrical nerve stimulation (TENS), neuromuscular electrical stimulation (NMES), and microcurrent stimulation (MCS). Each of these modalities delivers electrical impulses in a specific way and thereby achieving therapeutic, fitness and wellbeing related benefits. In effect, electrotherapy has been applied in a variety of contexts, and numerous studies have shown both in clinical and laboratory settings that it represents an effective and safe method to treat numerous conditions including cancer bone pain, chronic hip arthritis pain, neck and back pain, chronic pelvic floor pain, as well as acute, chronic and trauma pain. In addition, electrotherapy application brings about many other beneficial effects, which range from wound healing and tissues repair, and from increase in ATP and muscles mass to improvement in metabolism and physical performance.   

Electrotherapy comprises different modalities, including peripheral nerve stimulation (PNS) also known as transcutaneous electrical nerve stimulation (TENS), neuromuscular electrical stimulation (NMES), and microcurrent stimulation (MCS). Each of these modalities delivers electrical impulses in a specific way and thereby achieving therapeutic, fitness and wellbeing related benefits
Neuromuscular Electrical Stimulation (NMES)

NMES application elicits involuntary muscle contractions, and has been shown to bring about both health and fitness related benefits. These benefits are similar to those resulting from voluntary contractions occurring during physical exercise, including controlling type 2 diabetes and preventing the development of its complications.  Postprandial hyperglycaemia (an abnormal increase in blood glucose level after a meal) is an independent and dominant risk factor for cardiovascular disease and mortality in type 2 diabetes. Moreover, postprandial hyperglycaemia leads to the development of other complications, including nephropathy (kidneys disease), retinopathy (eye condition), and neuropathy (peripheral nerve damage). In contrast, it has been shown that control of postprandial blood glucose level is associated with reduced risk of cardiovascular disease, myocardial infarction and cerebral vascular disease. Therefore, it is clinically extremely important to treat postprandial hyperglycaemia, as it helps prevent type 2 diabetes complications. 

In a study conducted in Japan, NMES was applied to attenuate postprandial hyperglycaemia in type 2 diabetes patients.  A group of type 2 diabetes sedentary patients participated in the study, and prior to the intervention they underwent a routine assessment and testing that included plasma glucose, serum insulin and C-peptide (a compound produced in the pancreas along with insulin and they are released at the same time in equal amounts). Other tests included VO2 (volume of oxygen) consumption, and respiratory quotient or RQ (the ratio of CO2 produced to O2 consumed), and blood lactate. After the above pre-prandial (before a meal) tests were completed, all patients consumed a standardised meal containing 612 kcal (61% carbohydrate, 21% fat, and 18% protein). All patients took their medications as usual.  

Each patient participated in two sessions, and the above testing procedure was repeated before each session, as well as after, specifically at 30, 60, 90 and 120 minutes after the consumption of the standardised meal. One session consisted of 30 minutes NMES (experimental), and the other session consisted of complete rest (control).  The two sessions took place 30 minutes after consuming the meal, and were performed by the patients in random order, with an interval of at least one week between sessions. The results showed that 30 minutes session of NMES improves postprandial glucose level. Indeed, following the application of NMES blood glucose was significantly lower at the time point of 60, 90, and 120 minutes after meal, compared with control. Also, 120 minutes after consuming the meal, the C-peptide was significantly smaller as a result of the NMES session compared with control. Besides, NMES increased VO2, RQ and blood lactate concentration compared with control.

These findings can have enormous implication in combatting postprandial hyperglycaemia in type 2 diabetes patients. In effect, this study demonstrated that postprandial glucose level is significantly lower after NMES, compared with control. This highly desirable effect persisted until 120 minutes after the meal. Since postprandial hyperglycaemia is associated with mortality from diabetes complications and cardiovascular diseases, the results from this study have massive potential for prevention.  Besides, the significantly elevated RQ and blood lactate concentration clearly indicates an increased carbohydrate utilization and anaerobic glycolysis, induced by NMES. Another study had previously shown an increase in RQ and blood lactate concentration significantly greater in response to NMES compared with voluntary exercise, at the same exercise intensity in healthy young subjects. This can be explained by the fact that NMES recruits first type II muscle fibres, which have a larger axon diameter, lower electrical resistance and a greater capacity for glycogen utilization, compared with type I fibres. This fibres recruitment order is reversed compared to the one occurring during voluntary contraction. Consequently, such selective fast glycolytic fibres recruitment observed during NMES can enhance postprandial glucose uptake to a greater extent than voluntary exercise at the same intensity, both in healthy individuals and in patients with type 2 diabetes. Besides, the results from this study demonstrated that NMES also reduces postprandial C-peptide and insulin concentration, probably as a result of decreased blood glucose level. 

In addition, NMES administration augmented the energy expenditure significantly, as suggested by the increased oxygen consumption, and this contributes to combat obesity, very often associated with type 2 diabetes. Since all patients took the usual medication and consumed a standardised meal before the two sessions, therefore, all the beneficial effects observed can be attributed solely to NMES application.  It should be taken into consideration that in this study a single NMES session was applied to type 2 diabetes patients, and it is reasonable to assume that regular NMES application would have a cumulative effect and bring about even greater positive results.

These findings are in accordance with those from another study carried out in Ireland. In this study, type 2 diabetes patients underwent an 8-week NMES application, and the intervention consisted in eliciting rapid rhythmical contractions in the large lower extremity muscle groups. Patients completed six 1-hour training sessions per week (after their evening meal), for a period of 8 weeks. Following the intervention, the results showed a significant reduction in fasting plasma glucose level, a decrease in percentage body fat and an increase in peak isometric quadriceps torque. Lowering fasting plasma glucose level is strongly associated with reductions in the risk of complications associated with type 2 diabetes, such as neuropathy, nephropathy and retinopathy. The reduction in percentage body fat, it is likely to result from the aerobic training component of the NMES, which increases energy expenditure and fat oxidation. The reduction in fat mass leads to increased insulin sensitivity and consequently improves glycaemic control. Furthermore, other studies have shown that increased fat oxidation lowers plasma non-esterified free fatty acid level in obese type 2 diabetes patients, and therefore can reduce insulin resistance, hyperinsulinemia and improve glucose tolerance.

The 8 weeks NMES intervention improved aerobic fitness, and is likely to be beneficial to health, because it is a crucial determinant of insulin sensitivity of skeletal muscle and in subcutaneous adipose tissue. This is further supported by the improved glycaemic control observed following the NMES intervention.

The 8 weeks NMES intervention improved aerobic fitness, and is likely to have beneficial health, because it is a crucial determinant of insulin sensitivity of skeletal muscle and in subcutaneous adipose tissue. This is further supported by the improved glycaemic control observed following the NMES intervention. Moreover, increased aerobic power in type 2 diabetes patients is associated with improved atherogenic lipid profile, helping preventing atherosclerosis and other cardiovascular mortalities in this population. The increase in strength observed following the NMES intervention is also important, as it improved the ability to carry out daily tasks and the quality of life. A study conducted in Canada showed that NMES enhances glucose uptake in type 2 diabetes patients, and the results from another study showed a significant insulin sensitivity improvement after one week of NMES application.  

Besides, a case study of an insulin-dependent diabetes patient, who presented to a hospital in Singapore with low back pain, confirmed the many positive effects of electrotherapy. Initially the pain was treated with conventional analgesics. Subsequently, the patient was advised to apply PNS three times a day, for a duration of 10 minutes each session, which resulted in pain relief. After six days of PNS therapy, the patient started to experience symptoms of hypoglycaemia, which was confirmed by a blood test. The patient was advised to discontinue the PNS application and insulin, as well as to monitor and record his glucose level. As a result, the glucose level started to rise, and the routine insulin therapy was restarted. However, when PNS therapy was resumed, the hypoglycaemic response manifested again. As a result, insulin dosage was reduced to half of the patient’s daily requirement and the PNS application was reduced to two daily sessions. The patient was followed up for one month, and blood glucose was checked daily. Interestingly, despite halving the insulin dosage, plasma glucose level remained within the acceptable range throughout that period. 

Peripheral Nerve Stimulation Therapy (PNS)
PNS therapy is usually applied for pain relief, but in this case report, it also lowered blood glucose and reduced by 50% the patient’s daily insulin requirement

PNS therapy is usually applied for pain relief, but in this case report, it also lowered blood glucose and reduced by 50% the patient’s daily insulin requirement. These findings are not completely new, as a previous study showed that PNS applied on the ST36 and SP6 acupoints, prevented hyperglycaemia and increased the sensitivity of plasma insulin. Hyperglycaemia is a common result of stress signals caused by pain and surgical procedures. High level of stress is associated with increased cortisol level, which augments gluconeogenesis and glucose release, leading to elevated plasma glucose level. Thus, a plausible explanation for the hypoglycaemia observed following electrotherapy, is that PNS reduced stress through pain relief, in turn this led to diminished cortisol release and thereby decreasing plasma glucose. Besides, if the intensity of PNS application is sufficiently high, in addition to stimulating peripheral nerves, it also may activate some motoneurones, and thereby causing muscle contraction, especially type II (fast glycolytic) muscle fibres. The consequent increased muscle metabolism and glucose utilisation may have contributed to the hypoglycaemia observed following PNS application. The results of this case report are extremely important, as they demonstrate that PNS application can reduce both pain and the daily insulin requirement, in insulin-dependent patients.     

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, and is often associated with pain, affecting from 16% to 33% of diabetes patients. Patients with painful DPN have higher health care costs, as well as higher rate of work and activity impairment, and more frequent hospitalisations compared to diabetes patients not afflicted by painful DPN. Pharmacological relief of neuropathic pain is often insufficient. Besides, all pharmacologic therapies for PDN are associated with a number of potentially serious side effects. The intolerance to these medications can lead to the discontinuation of therapy or to a considerable reduction of the dosage. A meta-analysis of randomized controlled trials, evaluated the effectiveness of PNS on painful DPN. The meta-analysis found that PNS reduces pain and improves the overall neuropathic symptoms significantly, and without any adverse event. These results demonstrate that PNS application represents an efficacious and safe therapy for treating symptomatic DPN. In addition, the European Federation of Neurological Societies (EFNS) suggested that electrotherapy is safe and can be used as an adjunct intervention to treat pain. A number of other studies confirmed that PNS is effective for the treatment of painful DPN. A study conducted in Germany showed that electrotherapy decreases the symptoms of DPN, reduces diastolic blood pressure and biomarkers of stress. Also, other studies showed that electrotherapy improves PDN symptoms, chronic wounds and sleeping disturbances. 

PNS stimulates specific sensory nerves, and thereby activating two natural pain relief mechanisms that prevent the pain signals from reaching the brain, and also stimulating the production of the body’s natural pain killers. Compared with other treatments, PNS is a more natural approach to treat pain. Indeed, pain relief is achieved through a controlled flow of pure energy, without introducing foreign substances into the body or performing surgery.

Microcurrent Stimulation (MCS)

It has been shown that MCS application also brings about positive clinical outcomes and improves diabetes complications. An animal study revealed that MCS application improves diabetes-related pathological characteristics in liver, kidney and pancreas tissues. Diabetes can damage the peripheral vasculature causing poor blood circulation and perfusion, compromising the wound healing process. The findings from various studies in humans demonstrated that MCS application promotes wound healing, also in case where the repair mechanism is impaired by disease. Wound infection in diabetes patients, also impairs the ability to heal. A study conducted by Carley and co-workers showed that the wounds of patients treated with MCS healed 1.5 to 2.5 faster, compared with the control group. Moreover, wounds treated with MCS needed less debridement (removal of damaged tissue or foreign objects from wounds), the healed scars were more resilient, and no infection were observed. Other positive effects of MCS administration included reducing the patients discomfort at the wound site.  

A study conducted by Carley and co-workers showed that the wounds of patients treated with MCS healed 1.5 to 2.5 times faster, compared with the control group. Moreover, wounds treated with MCS needed less debridement (removal of damaged tissue or foreign objects from wounds), the healed scars were more resilient, and no infection were observed.

MCS is an electrotherapy modality that utilises electrical impulses in the micro ampere range (μA), which is below sensation threshold. Such electrical impulses are similar to those generated by the endogenous bioelectrical system. MCS efficacy stems from its ability to stimulate cellular physiology and growth. Disease or injury can cause an alteration in the normal bioelectrical potentials, leading to impairment of the healing process and inflammation. Moreover, bacterial growth at the injured site also affects negatively the healing process. All these factors are often the causes of impaired healing in diabetes patients. MCS administration augments the current flow at the injured site, improving energy level and promoting normal physiological functions in the traumatized area. Furthermore, the anti-bacterial and anti-inflammatory effects mediated by MCS also help re-establish homeostasis in the wounded tissues. These are the mechanisms activated by MCS application that promote wound healing and improve the symptoms in diabetes patients. 

Electrotherapy Represents an Efficacious and Safe Treatment Opportunity

Electrotherapy has a huge potential to make diabetes treatment both more clinically and cost effective, especially to those who are unable to perform voluntary exercise as a consequence of diabetes complications, excessive obesity, osteoarthritis or other conditions

Despite the enormous investment and relevant guidelines, the public health, medical and psychological burden of diabetes is huge and, if unaddressed, it is set to continue deteriorating exponentially. It should be taken into consideration that some conditions such as diabetes are very complex, making their treatment extremely challenging. Physical activity improves glucose metabolism in type 2 diabetes patients, however, adherence is often transient and/or partial. There is evidence suggesting that a large percentage of type 2 diabetes patients remain sedentary. Furthermore, type 2 diabetes is often associated with obesity and health conditions, which in many cases represent barriers to exercise participation.

As we have seen, a number of studies suggest that electrotherapy application in diabetes patients, brings about numerous positive effects, such as improving glucose metabolism, insulin sensitivity and physical fitness, as well as reducing insulin dosage and contributing to weight management, which is highly desirable for diabetes patients. Moreover, electrotherapy is effective in treating painful diabetic peripheral neuropathy, and improves wound healing. Unlike pharmacological therapy, the application of electrotherapy is virtually side effects free and cost effective, especially in the long term. Also, electrotherapy has numerous other advantages, as this approach is non-pharmacological, non-invasive, non-toxic, non-addictive and safe. The electrotherapy devices are small, light and portable. Furthermore, studies have shown that after a minimum of instructions and guidance, patients are able to self-administer electrotherapy effectively, from the comfort of their home as needed. Despite the well-established electrotherapy efficacy and its advantages, this intervention remains underutilised. 

However, it is extremely important to utilise optimally all the valuable qualities that characterise electrotherapy. Thus, it would be highly desirable to incorporate electrotherapy within the diabetes standard care routine, as it would be extremely beneficial to the patients, especially to those who are unable to perform voluntary exercise as a consequence of diabetes complications, excessive obesity, osteoarthritis or other conditions. Besides, electrotherapy administration could be used as a preventive measure in pre-diabetic individuals. In conclusion, electrotherapy has a huge potential to make diabetes treatment both more clinically and cost effective.
























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