New procedure may eliminate insulin dependency in type 2 diabetes

 a promising new treatment strategy for type 2 diabetes (T2D) that could significantly reduce or even eliminate the need for insulin therapy.
A promising new treatment strategy for type 2 diabetes (T2D) that could significantly reduce or even eliminate the need for insulin therapy.

Groundbreaking research presented at UEG Week 2024 reveals a promising new treatment for type 2 diabetes (T2D) that could significantly reduce or eliminate the need for insulin therapy.

This innovative approach combines a novel procedure called ReCET (Re-Cellularization via Electroporation Therapy) with semaglutide, resulting in the elimination of insulin therapy for 86% of patients.

Globally, type 2 diabetes (T2D) affects 422 million people, and obesity is recognized as a significant risk factor. While insulin therapy is commonly used to manage blood sugar levels in T2D patients, it can lead to side effects such as weight gain and further complicate diabetes management.

In the initial human trial, 14 participants between the ages of 28 and 75, with body mass indices ranging from 24 to 40 kg/m², underwent the ReCET procedure while under deep sedation. This treatment aims to enhance the body’s responsiveness to its own insulin. After the procedure, the participants followed a two-week isocaloric liquid diet, and then the dosage of semaglutide was gradually increased to 1mg per week.

At the 6- and 12-month follow-up, 86% of participants (12 out of 14) no longer needed insulin therapy, and this positive outcome persisted through the 24-month follow-up. During this time, all patients were able to maintain glycemic control, with HbA1c levels staying below 7.5%.

The maximum dose of semaglutide was well-tolerated by 93% of participants, one individual could not increase to the maximum dose due to nausea. All patients successfully completed the ReCET procedure, and no serious adverse effects were reported.

Dr Celine Busch, lead author of the study, commented, “These findings are very encouraging, suggesting that ReCET is a safe and feasible procedure that, when combined with semaglutide, can effectively eliminate the need for insulin therapy.”

“Unlike drug therapy, which requires daily medication adherence, ReCET is compliance-free, addressing the critical issue of ongoing patient adherence in the management of T2D. In addition, the treatment is disease-modifying: it improves the patient’s sensitivity to their own (endogenous) insulin, tackling the root cause of the disease, as opposed to currently available drug therapies, that are at best disease-controlling.”

Looking ahead, the researchers plan to conduct larger randomised controlled trials to further validate these findings. Dr Busch added, “We are currently conducting the EMINENT-2 trial with the same inclusion and exclusion criteria and administration of semaglutide, but with either a sham procedure or ReCET. This study will also include mechanistic assessments to evaluate the underlying mechanism of ReCET.”

Neurons look different in autistic children

Neuronal measurements could provide new insight into diagnosis and therapeutic interventions for autism
Neuronal measurements could provide new insight into diagnosis and therapeutic interventions for autism

New evidence suggests that the cells responsible for communication in the brain may have different structures in children with autism. Researchers at the Del Monte Institute for Neuroscience at the University of Rochester have found that neuron density in certain areas of the brain varies in children with autism compared to the general population.

“We have spent many years describing the broad characteristics of brain regions, such as thickness, volume, and curvature,” said Zachary Christensen, MD/PhD candidate at the University of Rochester School of Medicine and Dentistry, and the first author of the paper published today in Autism Research. “However, newer techniques in the field of neuroimaging for characterizing cells using MRI reveal new levels of complexity throughout development.”

Imaging provides new insight into brain development

Researchers analyzed brain imaging data from over 11,000 children aged 9-11. They compared brain scans of 142 children with autism to those of the general population and found lower neuron density in certain regions of the cerebral cortex. These regions are associated with memory, learning, reasoning, and problem-solving. On the other hand, they also found increased neuron density in the amygdala, a region responsible for emotions. The researchers compared the brain scans of children with autism not only to those without any neurodevelopmental diagnosis but also to a large group of children diagnosed with common psychiatric disorders like ADHD and anxiety. The results indicated that these differences are specific to autism.

“People diagnosed with autism often have to cope with other conditions such as anxiety, depression, and ADHD. These findings indicate that we now have a new set of measurements that show promise in identifying individuals with autism,” Christensen explained. “If we can reliably and easily identify unique differences in neuron structure in those with autism, it opens up opportunities to understand how autism develops. These measures could also be used to identify individuals with autism who may benefit from more targeted therapeutic interventions.”

Technology leverages what we know about the inner workings of the brain and autism

The advancement of technology has greatly improved the ability of investigators to observe precise details in neuronal structure. In the past, researchers could only observe structural differences in neural populations after death. The imaging data for this research was obtained from the Adolescent Brain Cognitive Development (ABCD) study database, which is the largest long-term study of brain development and child health. The University of Rochester is one of 21 national sites collecting data for this study, which began in 2015 and has significantly enhanced our understanding of adolescent brain health and development.

How to Handle a Terminal Diagnosis

How to talk to your doctor

Receiving a terminal diagnosis is one of the most challenging and emotional moments anyone can face. It brings with it a flood of emotions—fear, sadness, anger, and uncertainty—and can feel overwhelming, both for the individual diagnosed and for their loved ones.

While each person’s experience is unique, there are several steps that can help make this difficult journey more manageable with grace, courage, and a sense of control.

Allow Yourself to Process the News

It’s natural to feel plenty of emotions when first confronted with a terminal diagnosis. Denial, shock, anger, and grief are all common reactions. Take time to absorb the news and understand that there is no “right” way to feel. Everyone processes this type of information differently. Allow yourself to cry, express frustration, or feel confused without judgment.

Some may want to speak with close family and friends right away, while others may prefer to have time alone to reflect. Remember, this is your journey, and it’s important to give yourself permission to experience whatever emotions come up.

Understand Your Diagnosis and Treatment Options

Once the initial shock has passed, many find comfort in gaining a clear understanding of their condition. Speak with your healthcare provider about the specifics of your diagnosis, what to expect in the coming months, and what treatment options are available. Although curative treatments may no longer be possible, palliative care is available and can provide symptom relief and improve quality of life. Palliative care focuses on managing pain, discomfort, and emotional well-being, helping individuals live as fully as possible for as long as possible.

Some individuals may choose to pursue aggressive treatments to extend their lives, while others may prioritize comfort and quality of life by going to, for example, this Morris Care Home in Cheshire for palliative care. This is a deeply personal decision that should be made based on your own values and priorities.

Focus on Your Quality of Life

As you come to terms with a terminal diagnosis, the concept of “quality of life” becomes more important than ever. This is a time to focus on what brings you joy, peace, and comfort. For some, this may mean spending as much time as possible with loved ones. For others, it could mean traveling to a favorite place, enjoying favorite meals, or engaging in hobbies and passions.

Address Practical Matters

Facing a terminal diagnosis often brings practical concerns to the forefront. While it can be difficult to think about, planning for the future can help alleviate stress for both you and your loved ones. Some steps to consider include:

  • Advance Directives: This outlines your preferences for medical care, including whether you want life-prolonging treatments, resuscitation, or to be kept on life support.
  • Power of Attorney: Assigning a healthcare power of attorney ensures that someone you trust can make medical decisions on your behalf if you are unable to do so.
  • Will and Financial Planning: Updating your will, ensuring your financial affairs are in order, and discussing any final wishes with your family ensures your estate is handled according to your preferences.
  • Funeral or Memorial Planning: While it may be difficult to think about, making decisions about your funeral or memorial service in advance can relieve your family of having to make those choices during an emotional time.

Having these plans in place can allow you to focus more on the time you have left, knowing that your affairs are in order.

Communicate with Loved Ones

Honest and open communication with loved ones is essential during this time. Family members and friends may also be struggling with the news of your diagnosis, and it can be helpful to talk about your feelings, fears, and hopes together. While these conversations may be difficult, they can also bring a sense of closeness and understanding.

Some people find it helpful to write letters to their loved ones, sharing their memories, offering guidance, or expressing their love within them. This can be a meaningful way to leave a lasting message for those who mean the most to you.

Focus on Legacy and Meaning

As you face the reality of a terminal diagnosis, you may find comfort in thinking about your legacy—what you will leave behind for your loved ones and the impact you’ve made in your life. This can include personal legacies, such as the memories you’ve created with family and friends, as well as larger contributions, such as charitable work or projects you’ve been passionate about.

Some individuals choose to write memoirs, record videos, or create memory books to leave behind for their loved ones. Others may wish to contribute to causes they care about through donations or volunteering, even in small ways. Focusing on what has given your life meaning and how you want to be remembered can bring a sense of purpose during this difficult time.

Conclusion

Receiving a terminal diagnosis is one of life’s greatest challenges, but it doesn’t mean giving up hope. It’s an opportunity to focus on what matters most, seek support, and make decisions that reflect your values.

Alarming surge in global crisis of childhood overweight and obesity

Global Crisis of Childhood Overweight and Obesity

The harmful consequences of this epidemic are already evident: childhood hypertension and type 2 diabetes, among others. Researchers sound the alarm and discuss both challenges and potential solutions.  Credit Alex Dolce, Florida Atlantic University

Since 1990, the rise in childhood overweight and obesity has surged across every continent, almost doubling in prevalence. While the United States has the highest prevalence, other nations are not far behind.

In Southern Europe, including Greece, Italy, and Spain, 10 to 15% of children are obese. At the same time, Eastern European countries have somewhat lower rates but are experiencing a rapid increase that may soon match Southern Europe. Globally, Asia has nearly half of all overweight children under the age of 5, and Africa has one-quarter of such children. In Latin America, about 20% of children under 20 are overweight. Many developing countries face the dual challenge of both overweight/obesity and malnutrition in their children.

“Pediatric overweight and obesity have reached epidemic levels in the U.S. and are becoming a pandemic globally. These conditions lead to high blood pressure, type 2 diabetes and lipid disorders, which contribute to metabolic syndrome. In adults, these issues significantly increase the risks of heart attacks, stroke, liver disease, obstructive sleep apnea, arthritis and certain cancers – many of which are now occurring at younger ages,” said Charles H. Hennekens, M.D., first author and the first Sir Richard Doll Professor of Medicine and Preventive Medicine, FAU Schmidt College of Medicine. “Through coordinated clinical and public health efforts, we can address these troubling trends and work toward a healthier future for children and families globally.”

In the commentary, the authors report on the leading causes of this epidemic including high body mass index (BMI), which increases the risks of many serious health issues. In the U.S., a preschooler is considered overweight if their BMI exceeds the 85th percentile. Research shows that these children are at a significantly higher risk of being overweight during adolescence compared to those with a BMI at the 50th percentile. This underscores the misconception that children simply “outgrow” overweight issues.

In addition, the authors note that health care providers and public health practitioners face major challenges in boosting daily physical activity among children, which is crucial for increasing metabolic rates, lowering BMI, and reducing future risks of coronary heart disease.

“With declining physical education in schools and excessive time spent on electronic devices, many children fail to meet recommended activity guidelines. This sedentary behaviour contributes to overweight and obesity through poor diet, reduced sleep, and decreased physical activity,” said Panagiota “Yiota” Kitsantas, Ph.D.,

The authors also caution that while increasing levels of daily physical activity is necessary, it isn’t sufficient to make a major impact on the rates of childhood overweight and obesity. The rise of high sugar containing foods, along with consumption of ultra-processed foods also are major contributors.

“Nearly 70% of the average U.S.-based child’s diet is made up of ultra-processed foods,” said Hennekens. “Moreover, consumption of ultra-processed foods among children under 24 months is rising worldwide, triggering not only the potential of developing obesity but also decreased immunological protection.”

The authors say that more research is needed to pinpoint which components of ultra-processed foods contribute to weight gain in children. However, they warn that a diet high in ultra-processed foods is linked to rising rates of overweight and obesity, with schools being a major source of these foods.

“Evidence suggests that enhancing school lunch nutritional standards could help reduce obesity, particularly among low-income children,” said Kitsantas. “We recommend adopting school food policies that remove ultra-processed foods from menus and promote healthier alternatives, alongside educational programs on healthy eating, despite the challenges posed by external influences on children.”

Among the challenges highlighted in the commentary is the use of social media and advertising, which significantly affect children’s food choices and behaviors that include sharing unhealthy food posts and recognizing many unhealthy food brands upon exposure. 

“Despite recommendations from the World Health Organization and public health authorities to restrict food marketing aimed at children, few countries have implemented such measures,” said Hennekens. “The effectiveness of existing regulations in today’s media landscape is uncertain, creating an opportunity for health providers and public health practitioners to educate families about the impact of this advertising.”

The authors explain that addressing the rising pediatric obesity epidemic requires a multifaceted approach. In 2023, the American Academy of Pediatrics endorsed WHO guidelines and released their own recommendations for managing pediatric overweight and obesity. These guidelines advise health care providers and public health practitioners to tackle social determinants of health, use motivational interviewing to modify nutrition and activity behaviors, and consider pharmacotherapy or surgery to meet personalized patient goals.

However, the authors say that while there are approved drug therapies available, before prescribing pharmacologic options, maternal and child health care providers should employ therapeutic lifestyle changes.

“While the ultimate goal is prevention of pediatric overweight and obesity as well as metabolic syndrome, to paraphrase Voltaire, we should not ‘let the perfect be the enemy of the good,’” said Hennekens.

In conclusion, the authors urge leveraging all available resources to at least stabilize the rising rates of childhood obesity and its associated health issues. Ignoring these challenges could lead to an unprecedented global epidemic of childhood and adolescent obesity, with severe future health consequences, as seen in the U.S.

“Health care and public health professionals must collaborate across disciplines to address these issues with patients, families, communities and policymakers. United efforts can help reverse these troubling trends and ensure a healthier future for children worldwide,” said Kitsantas.

Neoself-antigens induce autoimmunity in lupus

Fig.

This study revealed that T cells can discriminate between self- and neoself-antigens and that neoself-reactive T cells are involved in causing autoimmune diseases. Hisashi Arase, Osaka University

Autoimmune diseases are widespread and notoriously difficult to treat. This is partly because why the immune system attacks its tissues in patients with these conditions remains poorly understood.

In a study recently published in Cell, researchers from Osaka University have revealed that the body’s proteins with unusual structures trigger immune cells to unleash a wave of inflammation that leads to autoimmunity.

Autoimmune diseases develop when the body’s immune system mistakenly attacks its tissues instead of fighting off foreign invaders like bacteria or viruses. However, it has long been a mystery why this happens, as the immune system has many checks and balances to ensure it only reacts to ‘non-self’ triggers.

“T cells have been thought to discriminate between small fragments of protein derived from self and non-self proteins presented on the major histocompatibility complex II (MHC-II), and ‘trained’ not to respond self-antigens” explains senior author of the study Hisashi Arase. “However, when the MHC-II is missing a crucial piece called the invariant chain (Ii), it can present larger, misfolded self-antigens, called herself-antigens, to T cells.”

Given that autoantibody to oneself-antigens are frequently found in patients with autoimmune diseases, the researchers explored T cell reactivity in patients with lupus and in mice, in which I was depleted from an adult. They also investigated the effect of Epstein–Barr virus (EBV) infection, a risk factor for lupus, on T cell reactivity to neoself-antigens.

“The results were striking,” says Shunsuke Mori, lead author. “Approximately 10% of clonally expanded T cell repertoire in lupus patients recognized neoself-antigens. Furthermore, induction of neoself-antigens induced lupus-like disease in mice, meaning that they mounted an immune response to the body’s tissues, thereby causing autoimmune disease.”

Furthermore, the researchers found that reactivation of EBV, which most people are infected with but are usually dormant, increases the presentation of oneself-antigens on MHC-II by downregulating the expression of Ii, triggering the activation of T cells directed against the body. This could explain why EBV reactivation is linked to the onset or exacerbation of lupus.

“Our findings demonstrate that T cells discriminate self- and neoself-antigens and do not recognize neoself-antigens as self-antigens, thus leading to the development of autoimmunity when neoself-antigens are presented on MHC-II,” says Arase.

This study substantially increases our understanding of the self-tolerance of T cells as well as the causes of autoimmune disease by identifying oneself-antigens as a distinct class of antigens that trigger an inappropriate immune response. This insight into why the body begins to attack itself could help develop new treatments for autoimmune disorders like lupus.