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Globally, diabetes affects more than 420 million people, of which, on average, 10% with type 1 diabetes and 90% with type 2 diabetes. In 2019, diabetes was the direct cause of 1.5 million deaths worldwide. Often diagnosed late, type 2 diabetes has serious long-term consequences, such as retinal damage leading to blindness, kidney failure or healing problems up to amputation. Recently, a team of American researchers showed the potential of bioelectronic medicine as an alternative or complement to drugs in the treatment of chronic diseases, and in particular type 2 diabetes.
People with type 2 diabetes secrete insulin, but this hormone is less effective in regulating the level of sugar in their blood — blood sugar. It remains abnormally high after a meal, which is the definition of diabetes. Gradually, the pancreas becomes exhausted in secreting increasing amounts of insulin. Also called fatty diabetes, or non-insulin-dependent diabetes, type 2 diabetes mainly affects people who are overweight or obese, sedentary, most often after 45 years of age. It represents 90% of cases of diabetes after 60 years.
A study by INSERM (National Institute of Health and Medical Research) estimates that 5% of the French population (about 2 million people) suffers from type 2 diabetes. The number of cases of type 2 diabetes diagnosed increases by more than 5% each year. Part of the increase is linked to the aging of the population. Another factor is a deleterious lifestyle, nutritional imbalances and physical inactivity leading to a general increase in weight and the number of people with obesity. Thus, in Western countries, the average age of onset of type 2 diabetes has decreased: cases of adolescents with this disease have even been reported in the United States. Another subject of alert: the recent increase in “medicated” diabetes, associated in particular with certain neuroleptics.
Unfortunately, there is no cure for diabetes. The reference treatment for type 2 diabetes is the optimization of lifestyle habits: weight loss if necessary, regular physical activity and a balanced diet may be sufficient to control blood sugar at first. In second intention, oral and/or injectable antidiabetics are prescribed to control blood sugar. When diabetes progresses, it may require the establishment of insulin treatment. But there are risks as to forgetting or taking too much of the treatment inducing respectively hyperglycaemia or hypoglycaemia, both of which are potentially fatal.
In addition, in adults, diabetes doubles or triples the risk of myocardial infarction and stroke. Each year, among the 10,000 diabetics hospitalized for a myocardial infarction, 1000 will die. Associated with reduced blood flow, diabetic neuropathy (nerve damage) (mostly affecting the extremities) increases the likelihood of developing ulcers, infections and, ultimately, amputations. Moreover, each year, there are no less than 9,000. In addition, diabetes is one of the main causes of kidney failure: each year, 3,000 diabetics start dialysis or undergo a kidney transplant, according to INSERM.
It is in this context that a team led by GE Research — a branch of General Electric including researchers from Yale School of Medicine, UCLA and the Feinstein Institutes for Medical Research — suggests that type 2 diabetes could be treated without medication, or at least that its onset could be prevented and reversed through bioelectronics. Their finding was published in the journal Biomedical engineering from nature.
Bioelectronics at the service of the nerves
Let’s go back to what bioelectronic systems are. They refer to innovations in so-called “electronic-electromagnetic-living” interfaces. The latter have the ability to take advantage of electrical signals – for example thanks to implants – in order to electrically stimulate the nerves of the peripheral nervous system. They show promise for the treatment of certain chronic diseases such as arthritis, diabetes or asthma. The results reported in this new study represent a milestone in the field of bioelectronic medicine.
This new, non-invasive treatment modulates the body’s nervous system by focusing high-frequency sound waves on specific sensory nerves in the liver. Ultrasound is known to stimulate particular neural pathways in organs (which may be associated with various diseases). The researchers found that their treatment method using ultrasound prevented or reversed type 2 diabetes in three different preclinical models: mice, rats and pigs. The technology is called “peripheral focused ultrasound stimulation” (pFUS).
First, the UCLA researchers designed a 3D scaffold to grow and grow neurons used in the study’s lab experiments. It consists of a hydrogel with microscopic pores in which neurons reside and grow, providing ample space for many dendrites and axons that link neurons together. The researchers adjusted the stiffness of the scaffold to optimal conditions for neurons and added small chains of amino acids (peptides) that nerve cells can adhere to.
This is how experiences in vitro showed that neurons can be activated and send signals when stimulated by ultrasound, due to the presence of sensors on the cell surface. These sensors respond to ultrasound-induced pressure changes.
Dino Di Carlo, professor of bioengineering and holder of the Armond professorship at UCLA, explained in a press release: Our studies indicate that focused ultrasound activates neurons via ion channels sensitive to mechanical forces. This is a whole new way to interface with our body and treat disease “.
Secondly, experiments live were performed on three preclinical animal models. Specifically, the researchers explain in a research briefing published on Nature : “ We used this technique to explore the stimulation of an area of the liver called the hepatic portal. This region contains the hepatoportal nerve plexus, which communicates information about glucose and nutrient status to the brain, but has been difficult to study because its nerve structures are too small to be separately stimulated with implanted electrodes. “. The study indicates that short, targeted bursts of pFUS in this area of the liver reversed the onset of hyperglycemia.
Ultrasounds, hope of treatment still being tested
As Raimund Herzog, a Yale School of Medicine endocrinologist working on the project, points out in a statement: Unfortunately, there are currently very few drugs that lower insulin levels. If our ongoing clinical trials confirm the promise of the preclinical studies reported in this article, and that ultrasound can be used to lower both insulin and glucose levels, ultrasound neuromodulation would represent an exciting and entirely new addition to the current treatment options for our patients “.
Sure enough, the study found that just three minutes of focused ultrasound each day was enough to maintain normal blood sugar levels in diabetic mice. Christopher Puleo, a biomedical engineer at GE Research who co-led the diabetes studies and corresponding author of the Nature Biomedical Engineeringsays: ” We have shown that ultrasound can be used to prevent or reverse diabetes in these preclinical studies. We are now in the midst of human feasibility trials with a group of type 2 diabetic subjects, which brings our work to clinical translation. “. The GE Research team also adds that other preclinical studies have been conducted to explore different doses and durations of ultrasound.
However, even if evidence of the efficacy of this treatment in humans is provided, technical obstacles hinder clinical deployment at the present time. Current ultrasound tools used to perform this type of pFUS technique require trained technicians. The researchers believe the technology exists to simplify and automate these systems for future use by patients at home. Nevertheless, the editors of the journal biomedical engineering from nature, in a comment accompanying the new publication, temper the enthusiasm generated by this new technique. Certainly, this innovation could lead to a new type of treatment for diabetes and underlines the therapeutic relevance of the brain-liver nerve pathways, but much remains to be done before getting there, which will require large investments.
Finally, while waiting for this technical feat, let’s recall that, according to the WHO, simple measures modifying the way of life would make it possible to avoid or delay the onset of type 2 diabetes, such as a healthy diet, regular physical activity and maintaining a healthy weight.