A new study from Karolinska Institutet shows that people with type 2 diabetes have lower protein levels that break down and convert creatine in the muscles. This leads to impaired function of the mitochondria, the cell’s ‘powerhouses’.
Creatine is a natural compound found in foods such as meat and fish. It is also a popular supplement for improving exercise performance, as it can make muscles work harder and longer before they become fatigued. Despite creatine’s recognized positive effects, previous studies have suggested a possible link between high blood creatine levels and an increased risk of type 2 diabetes. This has raised questions about whether creatine supplementation may contribute to that risk.
New research based on studies in both humans and mice shows that people with type 2 diabetes have lower protein levels in their muscles that metabolise and convert creatine—a protein called creatine kinase.
“This reduced protein level leads to impaired creatine metabolism in the muscle. This may explain why people with type 2 diabetes accumulate creatine in their blood,” says Anna Krook, Professor at the Department of Physiology and Pharmacology at Karolinska Institutet and the study’s principal investigator.
Scientists don’t know exactly what high creatine levels in the blood mean for the body, but they do know that they affect cells outside the cells.
“The findings indicate that impaired creatine metabolism is a consequence of type 2 diabetes rather than a cause of the disease,” says Anna Krook.
The study also shows that low levels of creatine kinase are linked to higher creatine levels in the blood and the impairing function of mitochondria in the muscle. Mitochondria, which convert nutrients into energy, function less well in muscle cells with reduced creatine kinase, leading to lower energy production and increased cell stress.
“This is quite consistent with the fact that people with type 2 diabetes have poorer energy metabolism. In the future, one possibility could be to regulate creatine kinase as part of treating metabolic diseases such as obesity and diabetes,” says Anna Krook.
An unexpected finding of the study was that changes in creatine kinase levels affected the appearance of mitochondria and also their ability to produce energy, regardless of the amount of creatine available.
“This suggests that although the main role of creatine kinase is to process creatine, it affects mitochondrial function in other ways,” explains David Rizo-Roca, the study’s first author.
“Our next step is to find the molecular mechanisms behind these effects,” he says.
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.”
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.
A microscopic look into a cell with MoS₂ nanoparticles Credit Dr Akhilesh Gaharwar/Texas A&M Engineering
We might take a vacation or relax at the spa when we need to recharge. But what if we could recharge at the cellular level, fighting against ageing and disease with the microscopic building blocks of the human body?
The ability to recharge cells diminishes as humans age or face diseases. Mitochondria, often called the cell’s powerhouse, are central to energy production. When mitochondrial function declines, it leads to fatigue, tissue degeneration, and accelerated ageing. Activities that once required minimal recovery now take far longer, highlighting these organelles’ role in maintaining vitality and overall health.
While current treatments for ailments related to ageing and diseases like type 2 diabetes, Alzheimer’s, and Parkinson’s focus on managing symptoms, Texas A&M researchers have taken a new approach to fighting the battle at the source: recharging mitochondrial power through nanotechnology.
Nanoflowers
Led by Dr. Kanwar Abhay Singh, a biomedical engineering postdoctoral associate in the Gaharwar Laboratory at Texas A&M, the team has developed molybdenum disulfide (MoS₂) nanoflowers. Named because of their flower-like structure, these nanoparticles contain atomic vacancies that can stimulate mitochondrial regeneration, helping cells generate more energy.
“These findings offer a future where recharging our cells becomes possible, extending healthy lifespans, and improving outcomes for patients with age-related diseases,” said Dr. Akhilesh Gaharwar, Tim and Amy Leach Professor and Presidential Impact Fellow in the Department of Biomedical Engineering at Texas A&M.
According to Gaharwar, the nanoflowers could offer new treatments for diseases like muscle dystrophy, diabetes, and neurodegenerative disorders by increasing ATP production, mitochondrial DNA, and cellular respiration. They discovered that the atomic vacancies in the nanoflowers stimulate the molecular pathways involved in mitochondrial cell replication.
Research collaborators include Texas A&M faculty and students. From the Department of Biophysics and Biochemistry, Dr. Vishal Gohil provided insights into the mechanisms that could drive the improvement of mitochondrial function.
“This discovery is unique,” Dr. Gohil said. “We are not just improving mitochondrial function; we are rethinking cellular energy entirely. The potential for regenerative medicine is incredibly exciting.”
Other Department of Biomedical Engineering contributors include Dr. Hatice Ceylan Koydemir, assistant professor, and Dr. Irtisha Singh, an affiliate assistant professor in the Department of Molecular and Cellular Medicine. Singh contributed computational analysis that revealed key pathways and molecular interactions responsible for the energy boost.
A Profound Discovery
“By leveraging advanced computational tools, we can decode the hidden patterns in cellular responses to these nanomaterials, unlocking new possibilities for precision medicine,” Singh said. “It’s like giving cells the right instructions at the molecular level to help them restore their own powerhouses — mitochondria.”
The next steps for the research team include identifying a method for delivering the nanoflowers to human tissue, with the goal of eventual clinical application.
“In science, it’s often the smallest details that lead to the most profound discoveries,” Gaharwar said. “By focusing on the unseen — like atomic vacancies in nanomaterials — we are uncovering new ways to solve big problems. Sometimes, the real breakthroughs come from digging deeper and looking beyond the obvious.”
Severe autoimmune conditions such as Type I diabetes, Addison’s disease, lupus and inflammatory bowel disease are between two to three times more common in women who have been diagnosed with premature ovarian insufficiency (POI) compared to the general population.
The research, published today (Thursday) in Human Reproduction, one of the world’s leading reproductive medicine journals, is the largest to investigate the link between autoimmune conditions and POI, has followed nearly 20,000 women for longer than any other study and is the only one to match women with POI with women of similar ages in the general population for comparison.
The researchers say their findings significantly strengthen the hypothesis that autoimmune processes play a “pivotal role” in the onset of POI.
POI occurs when ovaries no longer work properly and have stopped producing eggs in women younger than 40 years. Periods become irregular and then stop, and some women experience menopause symptoms.
Dr Susanna Savukoski, a gynaecology and obstetrics doctor at Oulu University Hospital and University of Oulu, Finland, led the study. She said: “Estimates of the prevalence of premature ovarian insufficiency of autoimmune origin have ranged from 4% to 50%. Our study has found that autoimmune diseases were two-to-three-fold more common in women diagnosed with POI at the time they were diagnosed, and the incidence of these diseases was two-to-three-fold higher during the first years after being diagnosed with POI, compared to a control group of similarly aged women from the general population. The incidence was higher than in the control group even more than a decade after being diagnosed with POI.”
Dr Savukoski and her colleagues analysed health data from Finland’s comprehensive registries. From the medicine reimbursement registry maintained by the Social Insurance Institution of Finland, they identified 3972 women who had been granted the right to full reimbursement for hormone replacement therapy (HRT) because of POI diagnosis under the age of 40 years between the years 1988 and 2017. Each woman with POI was matched with four women of similar ages, forming a control group of 15708 women. Both groups of women analysed data on severe autoimmune conditions – diseases diagnosed and treated in specialist health centres – between 1970 and 2017.
They found that among women who were diagnosed with POI, 223 women (5.6%) had been diagnosed with at least one autoimmune disorder before the date when reimbursement for HRT because of POI was granted, and 503 women (12.7%) were diagnosed with at least one autoimmune disorder after the date of HRT during the follow-up period.
Women were 2.6 times more likely to have an autoimmune disorder before a POI diagnosis when compared to the control group. Among women with POI, the risk of autoimmune conditions ranged from nearly double for over-active thyroid glands to almost 26 times for polyglandular autoimmune diseases – rare diseases of the hormone (or endocrine) system.
Women without existing autoimmune diseases at the time they were diagnosed with POI were nearly three times as likely to be diagnosed with an autoimmune disease in the following three years, with the risk decreasing but still significantly higher than in the control group during the follow-up period of at least 12 years.
Dr Savukoski said: “These findings reflect the fact that the association between POI and severe autoimmune diseases is strong and that the women with POI have long-term risk for autoimmune conditions. As with POI, severe autoimmune diseases typically manifest with significant symptoms and can have very unfavourable effects on general health, functional ability and quality of life. Luckily, there are good medication options available for many of these conditions.
“It’s important to stress that most women with POI do not develop severe autoimmune conditions, and most women with severe autoimmune diseases do not develop POI. However, medical professionals should be aware of the increased risk, and patients should also be informed about it.
“It should be noted that the risk is not the same for all autoimmune conditions: the association between POI and some autoimmune conditions, such as polyglandular autoimmune syndrome, Addison’s disease and vasculitis, was very strong – a ten to 26-fold risk of having these diseases among women with POI preceding their POI diagnosis compared to the controls – while the risk of having rheumatoid arthritis or hyperthyroidism was about two-fold.
“As POI threatens fertility at a young age, this indicates that women with an increased risk of the condition should be encouraged to try to conceive when they are young. However, some autoimmune diseases can significantly increase the risk of pregnancy complications, especially if therapeutic control is not good enough, and this should be considered in discussions with patients. Unfortunately, so far, there are no treatments available to prevent the development of POI or autoimmune diseases.”
The biological mechanisms underlying the association between POI and autoimmune diseases are not fully understood, especially as the mechanisms may differ depending on the disease.
“Future research should focus on finding detailed mechanisms of how POI develops in different autoimmune conditions. That would enhance the development of preventive treatments against POI of autoimmune origin and other autoimmune conditions as well,” said Dr Savukoski. “We are investigating whether long-term use of HRT can prevent other conditions developing among women with POI.”
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