Electroceuticals for the Metabolic Syndrome

Electroceuticals are emerging as a relevant novel therapeutic option for a variety of disorders beyond its established use as pacemakers in cardiology and in certain neurological disorders. Electroceuticals are currently being tested and developed among others for pain, cancer, autoimmune and inflammatory diseases as well as diabetes, and the metabolic syndrome ([Fig. 1]). This enthusiasm for novel electrical devices shared by both public funding institutions and industry is based largely on an unprecedented progress in 3 areas [1] [2] [3].

Fig. 1 Electroceuticals for the Metabolic Syndrome: Prevention & Therapy & Regeneration. Based on a figure found at http://www.servier.com/Powerpoint-image-bank. Usage covered under a Creative Commons CC-BY license. (Color figure available online only).

Firstly, neurobiologists are advancing rapidly in defining and mapping neural circuits employing novel technologies such as optogenetics and other molecular imaging techniques. Thus, it will become possible to relate more specific sets of nerve fibers and excitatory patterns to specific disorders and disease processes. This will allow to develop a more precise treatment with less side effects. Secondly, there is an impressive development in bioengineering and material sciences. The design of novel biocompatible and miniaturized devices will allow implantation with the help of novel technologies in minimally invasive surgery. This will make these devices more durable and more convenient for patients. Thirdly, perhaps not yet fully appreciated but maybe the most important innovations relate to cutting edge cellular communication technologies. Wireless communications with a significant reduction in round-trip latency of interaction will enable us to connect devices with the human body for a hitherto unimaginable exchange of information and data [4]. With the advent of the tactile internet, eventually tactile and neuronal steering and/or control of a device may be carried out while simultaneously seeing, feeling, or hearing its reactions. We are only beginning to understand the ground-breaking potential of this new tactile internet for medical technologies [4].

The epidemic rise of the metabolic syndrome with all its complications and comorbidities in virtually all populations around the globe clearly poses the number one challenge for our health care system today [5] [6].

The hypothalamus senses hormones and nutrients to regulate weight and energy balance. Recently, several peptides have been detected to play a major role in this brain-mediated regulation of food intake and fat selection [7] [8] [9] [10]. Furthermore, other forms of diet and lipids exert a differential regulation on insulin sensitivity and metabolism [11] [12].

What would we expect from an ideal treatment strategy for the metabolic syndrome and why could electroceuticals be a useful tool for better management of this epidemic disease?

First of all for the metabolic syndrome including type II diabetes we have left the narrow view of a glucocentric treatment path. A meaningful treatment strategy for these patients has to address all aspects of the syndrome including hyperglycemia, overweight, hypertension, and dyslipidemia. This is the only way to improve both morbidity and mortality in the most efficient way.

For this aim, electroceuticals may offer a good solution. Electrical devices may lower the blood pressure by targeting the carotid body and may lower body weight and blood sugar by gastric electrical stimulation [13] [14]. Furthermore, we now have learned that an appropriate treatment strategy for the metabolic syndrome needs to take into consideration 3 further key points:

1. The metabolic syndrome and the severity of its complications correlate with the degree of inflammation and immune dysregulation in the adipose tissue, vessels and elsewhere [15] [16].

2. There is a shared biology of the metabolic syndrome and mental disorders particularly depression clearly aggravating the progression and complications of both epidemic disorders [17].

3. Hypoglycemia as a consequence of insulin therapy for the patients with metabolic syndrome are a more common phenomenon and bear a much higher risk for cardiovascular and neurological long-term complications as has been acknowledged so far [18] [19].

For all 3 challenges in the management of the metabolic syndrome, electroceuticals may offer unexpected advantages. Thus, vagal stimulation has recently been shown to modify immune function with the potential for a beneficial suppression of the chronic inflammatory process in the metabolic syndrome [20].

Secondly, vagal stimulation following gastric electrical stimulation has been shown to exert anti-depressive actions [21] [22]. This is in contrast to recent anti-obesity drugs or bariatric surgery that have the problem of aggravating or triggering depression [23] [24].

Interestingly, gastric stimulation in obese subjects activates the hippocampus and other central regions involved in brain reward circuitry [25]. Similar brain circuits are shared between the enhanced motivational drive for food and drugs seen in obesity and drug-addicted subjects. Electroceuticals in combination with novel applications of the tactile internet may therefore be designed to tackle the “root of all evil” in the obesity epidemic. This includes the decline in physical activity in an increasingly computerized sedentary environment and the new role for food not to fulfil basic nutritional requirements but as a comfort drug to mitigate our chronically elevated stress levels [26].

Finally, electroceuticals targeting the satiety centers in the brain have the potential to reduce hyperglycemia without inducing hypoclycemia and/or further weight gain as with insulination [13] [27] [28]. In patients with beta cell failure combining electroceutical devices with novel oxygenated beta cell containing bioartificial organs may constitute a fascinating avenue to regenerate both cellular and metabolic functions [29].

The study performed by Lebovitz H. et al [30] (presented in this issue) had the following objectives: 1. Evaluation of long-term benefit of nonexcitatory gastric electrical stimulation (GES) by the DIAMOND device on glycemic control and body weight in patients with type 2 diabetes inadequately controlled with oral agents. 2. Determination of the magnitude of the modulating effects of fasting plasma triglyceride (FTG) levels on these effects of GES. The scientists identified that GES improves glycemic control and reduces body weight by a triglyceride-dependent mechanism in patients with type 2 diabetes inadequately controlled on oral agents. It is postulated that this is through a gut-brain interaction that modulates effects on the liver and pancreatic islets [30].

Therefore, electroceuticals will not fully replace pharmaceuticals but offer a promising additional therapeutic option for the metabolic syndrome. We will need to design novel clinical trials combining existing and newly developed drugs with electroceutical devices to offer an optimal treatment for our patients.

• References

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