An Australian study has found that drinking just one can of artificially sweetened soft drink a day may increase the risk of developing type 2 diabetes by 38 per cent.
Surprisingly, that risk for artificially sweetened soft drink is even higher than for those who consume sugar-sweetened beverages, such as regular soft drinks, where the risk was found to be 23 per cent higher.
The research, conducted by a team from Monash University together with RMIT University and the Cancer Council Victoria, followed more than 36 000 Australian adults over nearly 14 years.
The study – led by Distinguished Professor Barbora de Courten from Monash University and RMIT University, Associate Professor Allison Hodge, from the Cancer Council Victoria, and Monash PhD student Robel Hussen Kabthymer, and published in Diabetes & Metabolism – adds to growing global concern about the health effects of both sugary and artificially sweetened drinks.
“Drinking one or more of these beverages each day – whether sweetened with sugar or artificial substitutes – was linked to a significantly higher chance of developing type 2 diabetes,” said Mr Hussen Kabthymer.
Professor de Courten, senior author on the study, said the findings challenge the common assumption that artificially sweetened beverages are a safer choice.
“Artificial sweeteners are often recommended to people at risk of diabetes as a healthier alternative, but our results suggest they may pose their own health risks,” she said.
While the link between sugary drinks and diabetes could largely be explained by obesity, the connection between artificially sweetened drinks and type 2 diabetes remained strong even after adjusting for body weight, suggesting a potentially direct effect on metabolism.
Professor de Courten said the findings have important implications for public health policy.
“We support measures like sugary drink taxes, but our study shows we also need to pay attention to artificially sweetened options. These are often marketed as better for you; yet may carry their own risks. Future policies should take a broader approach to reducing intake of all non-nutritive beverages.”
The study analysed data from the long-running Melbourne Collaborative Cohort Study, also known as Health 2020, involving participants aged 40–69 years, and adjusted for diet, exercise, education, and health history.
Prediabetes affects a third of people in the United States and most of them will develop Type 2 diabetes, yet effective dietary intervention strategies remain limited. Pistachios have shown promise in improving markers of diet quality, yet little is known about how they influence the gut microbiome – a key player in glucose regulation and inflammation.
A new study led by Kristina Petersen, associate professor of nutritional sciences at Penn State, determined that nighttime pistachio consumption affects gut bacteria in adults with prediabetes. Though the potential therapeutic implications of the findings remain unclear, according to Petersen, they may prove significant for people who are working to improve their metabolic health.
The findings, published in the journal Current Developments in Nutrition, suggested that replacing a traditional carbohydrate-based bedtime snack with pistachios may reshape the gut microbiome. A previous study by these researchers demonstrated that pistachios have a similar effect on blood glucose as 15 to 30 grams of carbohydrates.
“Pistachios seem to be able to meaningfully shift the gut microbial landscape in adults with prediabetes especially when consumed as a nighttime snack.”
Kristina Petersen, associate professor of nutritional sciences at Penn State
“A common dietary recommendation for individuals with prediabetes is to consume a nighttime snack consisting of 15 to 30 grams of carbohydrates to help regulate overnight and morning blood glucose levels,” said Terrence Riley, lead author of this research who earned his doctorate in nutritional sciences at Penn State and currently works as a postdoctoral research fellow at Louisiana State University. “As an example, you could eat one or two slices of whole grain bread.”
Researchers observed that consuming about two ounces of pistachios each night for 12 weeks resulted in significantly different stool microbial community profiles compared to those who consumed the recommended 15 to 30 grams of a carbohydrate snack. Specific bacterial groups, including Roseburia and members of the Lachnospiraceae family – known as “good” bacteria that produces beneficial short-chain fatty acids like butyrate – were more abundant following the pistachio condition.
According to Petersen, butyrate serves as a primary energy source for colon cells, helps maintain the gut barrier and supports anti-inflammatory processes.
“Pistachios seem to be able to meaningfully shift the gut microbial landscape in adults with prediabetes especially when consumed as a nighttime snack,” Petersen said. “These microbiome changes may offer other long-term health benefits – potentially helping to slow the development of Type 2 diabetes or to reduce systemic inflammation – which we hope to explore in future research.”
The study involved 51 adults with prediabetes and was conducted over two 12-week periods separated by a break, so the effects of the first part of the trial would not affect the second part. By the end of the study, all participants received both treatments. Stool samples were collected and analysed using 16S rRNA gene sequencing, a technique that can help classify bacteria based on their genetic makeup.
Petersen noted that participants who ate pistachios also experienced reductions in several bacterial groups that have been linked to less favorable metabolic outcomes.
“Levels of Blautia hydrogenotrophica – a bacterium that helps produce compounds that can build up in the blood and harm kidney and heart health – were lower after pistachio consumption,” Petersen said. “Levels of Eubacterium flavonifractor, which breaks down beneficial antioxidant compounds from foods like pistachios, also decreased.”
Petersen added that the strength of this study is the design used – a randomised crossover clinical trial, in which all participants receive both treatments in a randomised order. By including all participants in the pistachio group and the standard care group, the study helped the researchers better understand how specific foods like pistachios can influence the gut microbiome.
While the study demonstrated shifts in gut bacteria, it remains unclear whether these changes directly translate to improvements in health – a question that requires further research, Petersen said.
New research from investigators at Mass General Brigham suggests that a commonly used type 2 diabetes medication is linked to a higher rate of heart-related conditions compared to medications that hit other targets. The study examined nationwide data from nearly 50,000 patients treated with different sulfonylureas and found that glipizide – the most widely used drug in the US within this category, but not available in South Africa – was linked to higher incidence of heart failure, related hospitalisation and death compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Results are published in JAMA Network Open.
“Patients with type 2 diabetes are at heightened risk of adverse cardiovascular incidents such as stroke and cardiac arrest,” said corresponding author Alexander Turchin, MD, MS, of the Division of Endocrinology at Brigham and Women’s Hospital (BWH), a founding member of the Mass General Brigham healthcare system. “While sulfonylureas are popular and affordable diabetes medications, there is a lack of long-term clinical data on how they affect cardiac health in comparison to more neutral alternatives like dipeptidyl peptidase 4 inhibitors.”
Turchin and co-authors emulated a target trial by analysing electronic health records and insurance claims data from the BESTMED consortium. The cohort included 48 165 patients with type 2 diabetes and moderate cardiovascular risk who received care at 10 different study sites across the country, including BWH, as well as those covered by two different national health insurance plans.
The researchers studied the five-year risk of major adverse cardiovascular events in patients treated with different sulfonylureas (glimepiride, glipizide or glyburide) or DPP4i in addition to metformin, a primary diabetes medication. They found that glipizide was associated with a 13% increase in cardiovascular risk when compared to DPP4i, while glimepiride and glyburide led to relatively smaller and less clear effects, respectively. The authors propose that further research is needed to uncover the underlying mechanisms.
“Our study underscores the importance of evaluating each drug in a particular pharmacological class on its own merits,” said Turchin.
Children born to obese mothers are at higher risk of developing metabolic disorders, even if they follow a healthy diet themselves. A new study from the University of Bonn published in the journal Nature offers an explanation for this phenomenon. In obese mice, certain cells in the embryo’s liver are reprogrammed during pregnancy. This leads to long-term changes in the offspring’s metabolism. The researchers believe that these findings could also be relevant for humans.
The team focused on the so-called Kupffer cells. These are macrophages that help protect the body as part of the innate immune system. During embryonic development, they migrate into the liver, where they take up permanent residence. There, they fight off pathogens and break down ageing or damaged cells.
“But these Kupffer cells also act as conductors,” explains Prof Dr Elvira Mass from the LIMES Institute at the University of Bonn. “They instruct the surrounding liver cells on what to do. In this way, they help ensure that the liver, as a central metabolic organ, performs its many tasks correctly.”
Changing the tune: From Beethoven to Vivaldi
It appears, however, that it is this conducting function that is changed by obesity. This is what mouse experiments carried out by Mass in cooperation with other research groups at the University of Bonn suggest. “We were able to show that the offspring of obese mothers frequently developed a fatty liver shortly after birth,” says Dr Hao Huang from Mass’s lab. “And this happened even when the young animals were fed a completely normal diet.”
The cause of this disorder seems to be a kind of “reprogramming” of the Kupffer cells in the offspring. As a result, they send out molecular signals that instruct the liver cells to take up more fat. Figuratively speaking, they no longer conduct one of Beethoven’s symphonies but rather a piece by Vivaldi.
This shift already seems to occur during embryonic development and is triggered by metabolic products from the mother. These activate a kind of metabolic switch in the Kupffer cells and change the way these cells direct liver cells in the long term. “This switch is a so-called transcription factor,” says Mass. “It controls which genes are active in Kupffer cells.”
No fatty liver without the molecular switch
When the researchers genetically removed this switch in the Kupffer cells during pregnancy, the offspring did not develop a fatty liver. Whether this mechanism could also be targeted with medication is still unclear. The teams now plan to investigate this in follow-up studies.
If new treatment approaches emerge from this, it would be good news. The altered behaviour of the Kupffer cells likely has many negative consequences. Fat accumulation in the liver, for example, is accompanied by strong inflammatory responses. These can cause increasing numbers of hepatocytes to die and be replaced with scar tissue, resulting in fibrosis. At the same time, the risk that hepatocytes degenerate and become cancerous increases.
“It is becoming ever more evident that many diseases in humans already begin at a very early developmental stage,” says Mass, who is also spokesperson for the transdisciplinary research area “Life & Health” and a board member of the “ImmunoSensation2” Cluster of Excellence at the University of Bonn. “Our study is one of the few to explain in detail how this early programming can happen.”
Intermittent energy restriction, time-restricted eating and continuous energy restriction can all improve blood sugar levels and body weight in people with obesity and type 2 diabetes, according to a study being presented Sunday at ENDO 2025, the Endocrine Society’s annual meeting in San Francisco, Calif.
“This study is the first to compare the effects of three different dietary interventions intermittent energy restriction (IER), time-restricted eating (TRE) and continuous energy restriction (CER) in managing type 2 diabetes with obesity,” said Haohao Zhang, PhD, chief physician at The First Affiliated Hospital of Zhengzhou University in Zhengzhou, China.
Although researchers identified improved HbA1c levels, and adverse events were similar across the three groups, the IER group showed greater advantages in reducing fasting blood glucose, improving insulin sensitivity, lowering triglycerides, and strengthening adherence to the dietary interventions.
“The research fills a gap in directly comparing 5:2 intermittent energy restriction with a 10-hour time-restricted eating in patients with obesity and type 2 diabetes. The findings provide scientific evidence for clinicians to choose appropriate dietary strategies when treating such patients,” Zhang says.
Zhang and colleagues performed a single-centre, randomised, parallel-controlled trial at the First Affiliated Hospital of Zhengzhou University from November 19, 2021 to November 7, 2024.
Ninety patients were randomly assigned in a 1:1:1 ratio to the IER, TRE or CER group, with consistent weekly caloric intake across all groups. A team of nutritionists supervised the 16-week intervention.
Of those enrolled, 63 completed the study. There were 18 females and 45 males, with an average age of 36.8 years, a mean diabetes duration of 1.5 years, a baseline BMI of 31.7kg/m², and an HbA1c of 7.42%.
At the end of the study, there were no significant differences in HbA1c reduction and weight loss between the IER, TRE and CER groups. However, the absolute decrease in HbA1c and body weight was greatest in the IER group.
Compared to TRE and CER, IER significantly reduced fasting blood glucose and triglycerides and increased the Matsuda index, a measure of whole-body insulin sensitivity. Uric acid and liver enzyme levels exhibited no statistically significant changes from baseline in any study group.
Two patients in the IER group and the TRE group, and three patients in the CER group, experienced mild hypoglycemia.
The IER group had the highest adherence rate (85%), followed by the CER group at 84% and the TRE group at 78%. Both the IER and CER groups showed statistically significant differences compared with the TRE group.
Zhang said these findings highlight the feasibility and effectiveness of dietary interventions for people who have obesity and type 2 diabetes.
The new implant carries a reservoir of glucagon that can be stored under the skin and deployed during an emergency — with no injections needed.
Caption:A new implantable device carries a reservoir of glucagon that can be stored under the skin and could save diabetes patients from dangerously low blood sugar.
Image: Courtesy of the researchers
For people with Type 1 diabetes, developing hypoglycaemia, or low blood sugar, is an ever-present threat. When glucose levels become extremely low, it creates a life-threatening situation for which the standard treatment of care is injecting a hormone called glucagon.
As an emergency backup, for cases where patients may not realise that their blood sugar is dropping to dangerous levels, MIT engineers have designed an implantable reservoir that can remain under the skin and be triggered to release glucagon when blood sugar levels get too low.
This approach could also help in cases where hypoglycaemia occurs during sleep, or for diabetic children who are unable to administer injections on their own.
“This is a small, emergency-event device that can be placed under the skin, where it is ready to act if the patient’s blood sugar drops too low,” says Daniel Anderson, a professor in MIT’s Department of Chemical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES), and the senior author of the study. “Our goal was to build a device that is always ready to protect patients from low blood sugar. We think this can also help relieve the fear of hypoglycaemia that many patients, and their parents, suffer from.”
The researchers showed that this device could also be used to deliver emergency doses of epinephrine, a drug that is used to treat heart attacks and can also prevent severe allergic reactions, including anaphylactic shock.
Siddharth Krishnan, a former MIT research scientist who is now an assistant professor of electrical engineering at Stanford University, is the lead author of the study, which appears today in Nature Biomedical Engineering.
Emergency response
Most patients with type 1 diabetes use daily insulin injections to help their body absorb sugar and prevent their blood sugar levels from getting too high. However, if their blood sugar levels get too low, they develop hypoglycaemia, which can lead to confusion and seizures, and may be fatal if it goes untreated.
To combat hypoglycaemia, some patients carry preloaded syringes of glucagon, a hormone that stimulates the liver to release glucose into the bloodstream. However, it isn’t always easy for people, especially children, to know when they are becoming hypoglycaemic.
“Some patients can sense when they’re getting low blood sugar, and go eat something or give themselves glucagon,” Anderson says. “But some are unaware that they’re hypoglycaemic, and they can just slip into confusion and coma. This is also a problem when patients sleep, as they are reliant on glucose sensor alarms to wake them when sugar drops dangerously low.”
To make it easier to counteract hypoglycaemia, the MIT team set out to design an emergency device that could be triggered either by the person using it, or automatically by a sensor.
The device, which is about the size of a quarter, contains a small drug reservoir made of a 3D-printed polymer. The reservoir is sealed with a special material known as a shape-memory alloy, which can be programmed to change its shape when heated. In this case, the researcher used a nickel-titanium alloy that is programmed to curl from a flat slab into a U-shape when heated to 40 degrees Celsius.
Like many other protein or peptide drugs, glucagon tends to break down quickly, so the liquid form can’t be stored long-term in the body. Instead, the MIT team created a powdered version of the drug, which remains stable for much longer and stays in the reservoir until released.
Each device can carry either one or four doses of glucagon, and it also includes an antenna tuned to respond to a specific frequency in the radiofrequency range. That allows it to be remotely triggered to turn on a small electrical current, which is used to heat the shape-memory alloy. When the temperature reaches the 40-degree threshold, the slab bends into a U shape, releasing the contents of the reservoir.
Because the device can receive wireless signals, it could also be designed so that drug release is triggered by a glucose monitor when the wearer’s blood sugar drops below a certain level.
“One of the key features of this type of digital drug delivery system is that you can have it talk to sensors,” Krishnan says. “In this case, the continuous glucose-monitoring technology that a lot of patients use is something that would be easy for these types of devices to interface with.”
Reversing hypoglycaemia
After implanting the device in diabetic mice, the researchers used it to trigger glucagon release as the animals’ blood sugar levels were dropping. Within less than 10 minutes of activating the drug release, blood sugar levels began to level off, allowing them to remain within the normal range and avert hypoglycaemia.
The researchers also tested the device with a powdered version of epinephrine. They found that within 10 minutes of drug release, epinephrine levels in the bloodstream became elevated and heart rate increased.
In this study, the researchers kept the devices implanted for up to four weeks, but they now plan to see if they can extend that time up to at least a year.
“The idea is you would have enough doses that can provide this therapeutic rescue event over a significant period of time. We don’t know exactly what that is — maybe a year, maybe a few years, and we’re currently working on establishing what the optimal lifetime is. But then after that, it would need to be replaced,” Krishnan says.
Typically, when a medical device is implanted in the body, scar tissue develops around the device, which can interfere with its function. However, in this study, the researchers showed that even after fibrotic tissue formed around the implant, they were able to successfully trigger the drug release.
The researchers are now planning for additional animal studies and hope to begin testing the device in clinical trials within the next three years.
“It’s really exciting to see our team accomplish this, which I hope will someday help diabetic patients and could more broadly provide a new paradigm for delivering any emergency medicine,” says Robert Langer, the David H. Koch Institute Professor at MIT and an author of the paper.
Other authors of the paper include Laura O’Keeffe, Arnab Rudra, Derin Gumustop, Nima Khatib, Claudia Liu, Jiawei Yang, Athena Wang, Matthew Bochenek, Yen-Chun Lu, Suman Bose, and Kaelan Reed.
The research was funded by the Leona M. and Harry B. Helmsley Charitable Trust, the National Institutes of Health, a JDRF postdoctoral fellowship, and the National Institute of Biomedical Imaging and Bioengineering.
A healthy lifestyle has important benefits, but weight alone might not give an adequate picture of someone’s health, say experts
Source: Pixabay CC0
Focusing solely on achieving weight loss for people with a high body mass index (BMI) may do more harm than good, argue experts in The BMJ.
Dr Juan Franco and colleagues say, on average, people with high weight will not be able to sustain a clinically relevant weight loss with lifestyle interventions, while the potential harms of weight loss interventions, including the reinforcement of weight stigma, are still unclear.
They stress that a healthy lifestyle has important benefits, but that weight alone might not give an adequate picture of someone’s health, and say doctors should provide high quality, evidence based care reflecting individual preferences and needs, regardless of weight.
Lifestyle interventions that focus on restricting an individual’s energy intake and increasing their physical activity levels have for many decades been the mainstay recommendation to reduce weight in people with obesity, explain the authors.
However, rigorous evidence has indicated that these lifestyle interventions are largely ineffective in providing sustained long term weight loss and reducing cardiovascular events (eg, heart attacks and strokes) or death.
Even though a healthy lifestyle provides important benefits, acknowledging that weight alone might not give an adequate picture of someone’s health, and recognising the limitations of lifestyle interventions for weight loss, could pave the way for more effective and patient centred care, they say.
Focusing on weight loss might also contribute to societal weight bias – negative attitudes, assumptions, and judgments about people based on their weight – which may not only have adverse effects on mental health but may also be associated with disordered eating, the adoption of unhealthy habits, and weight gain, they add.
They point out that recent clinical guidelines reflect the growing recognition that weight is an inadequate measure of health, and alternative approaches, such as Health at Every Size (HAES), acknowledge that good health can be achieved regardless of weight loss and have shown promising results in improving eating behaviours.
While these approaches should be evaluated in large clinical trials, doctors can learn from them to provide better and more compassionate care for patients with larger bodies, they suggest.
“Doctors should be prepared to inform individuals seeking weight loss about the potential benefits and harms of interventions and minimise the risk of developing eating disorders and long term impacts on metabolism,” they write. “Such a patient centred approach is likely to provide better care by aligning with patient preferences and circumstances while also reducing weight bias.”
They conclude: “Doctors’ advice about healthy eating and physical activity is still relevant as it may result in better health. The main goal is to offer good care irrespective of weight, which means not caring less but rather discussing benefits, harms, and what is important to the patient.”
Scientists have produced the first detailed characterisation of the changes that weight loss causes in human fat tissue by analysing hundreds of thousands of cells. They found a range of positive effects, including clearing out of damaged, ageing cells and increased metabolism of harmful fats.
The researchers say the findings help to better understand how weight loss leads to health improvements at a molecular level. In the future this could help to inform the development of therapies for diseases such as type 2 diabetes.
The study
The study, published in Nature, compared samples of fat tissue from healthy weight individuals with samples from people with severe obesity, meaning a BMI over 35, undergoing bariatric weight loss surgery.
The weight loss group had fat samples taken during surgery and more than five months after surgery, at which point they had lost an average of 25kg.
Lipid recycling
The researchers, who were from the Medical Research Council (MRC) Laboratory of Medical Sciences and Imperial College London, analysed gene expression in more than 170,000 cells that made up the fat tissue samples, from 70 people.
They unexpectedly found that weight loss triggers the breakdown and recycling of fats called lipids.
This recycling process could be responsible for burning energy and reversing the harmful build-up of lipids in other organs like the liver and pancreas.
The researchers say that further study will be needed to establish if lipid recycling is linked to the positive effects of weight loss on health, such as remission of type 2 diabetes.
Senescent cells
They also found that the weight loss cleared out senescent cells, which are ageing and damaged cells that accumulate in all tissues.
The senescent cells cause harm because they no longer function properly and release signals that lead to tissue inflammation and scarring.
Immune system
In contrast, the researchers found that weight loss did not improve the effects of obesity on certain aspects of the immune system.
They found that inflammatory immune cells, which infiltrated the fat of people with obesity, did not fully recover even after weight loss.
This type of inflammatory cell memory could be harmful in the long term if people regain weight.
Detailed map of what drives health benefits
Dr William Scott, from the MRC Laboratory of Medical Sciences and from Imperial College London, who led the study, said:
We’ve known for a long time that weight loss is one of the best ways to treat the complications of obesity, such as diabetes, but we haven’t fully understood why. This study provides a detailed map of what may actually be driving some of these health benefits at a tissue and cellular level.
Fat tissues have many underappreciated health impacts, including on blood sugar levels, body temperature, hormones that control appetite, and even reproductive health.
We hope that new information from studies like ours will start to pave the way for developing better treatments for diabetes and other health problems caused by excess body fat.
The skeletal muscles of men and women process glucose and fats in different ways. A recently published study now provides the first comprehensive molecular analysis of these differences. The results possibly give an explanation why metabolic diseases such as diabetes manifest differently in women and men – and why they respond differently to physical activity.
Skeletal muscles are far more than just “movement driving motors.” They play a central role in glucose metabolism and therefore also in the development of type 2 diabetes. This is due to the fact that around 85% of insulin-dependent glucose uptake takes place in the muscles. This means that if muscle cells react less sensitively to insulin, for example in the case of insulin resistance, glucose is less easily absorbed from the blood. This process is specifically counteracted by physical activity.
Women’s and Men’s Muscles Work Differently
The degree to which muscles work differently in women and men has long been underestimated. It is precisely this issue which has now been investigated by researchers at the Institute for Diabetes Research and Metabolic Diseases at Helmholtz Munich, the University Hospital of Tübingen and the German Center for Diabetes Research (DZD) e.V. The researchers, led by Dr Simon Dreher and Prof Cora Weigert, examined muscle biopsies from 25 healthy but overweight adults (16 women, 9 men) aged around 30 years. The test subjects had not taken part in regular sporting activities beforehand. Over a period of eight weeks, they completed one hour of endurance training three times a week, consisting of 30 minutes of cycling and 30 minutes of walking on the treadmill.
Muscle samples were taken before they started, after they had the first training session and at the end of the program. Using state-of-the-art molecular biological methods, including epigenome, transcriptome and proteome analyses, the team investigated sex-specific differences at various levels.
Men React with more Stress to Exercise
The result: The first training session triggered a stronger stress response at the molecular level in men, which became manifest in the increased activation of stress genes and the increase in the muscle protein myoglobin in the blood. In addition, male muscles showed a distinct pattern of what are called fast-twitch fibers, which are designed for short-term, intensive exercise and preferably use glucose as an energy source.
Women had significantly higher amounts of proteins that are responsible for the absorption and storage of fatty acids: an indication of more efficient fat utilisation. After eight weeks of regular endurance training, the muscles of both sexes matched and the muscle fibre-specific differences decreased. At the same time, women and men produced more proteins that promote the utilisation of glucose and fat in the mitochondria.
“These adjustments indicate an overall improvement in metabolic performance, which can help to reduce the risk of type 2 diabetes,” says Weigert. “In future, our new findings might help to better predict individual diabetes risks and tailor recommendations for exercise therapies more specifically to women and men.”
The scientists next want to investigate the role sex hormones play in these differences – and how hormonal changes in old age influence the risk of metabolic diseases.
Original publication
Dreher et al., 2025: Sex differences in resting skeletal muscle and the acute and long-term response to endurance exercise in individuals with overweight and obesity. Molecular Metabolism. DOI: 10.1016/j.molmet.2025.102185
About the scientists
Prof. Cora Weigert is head of the research group “Molecular Diabetology and Exercise” at the Institute for Diabetes Research and Metabolic Diseases at Helmholtz Munich and Professor at the University of Tübingen.
Dr. Simon Dreher is scientist at the Institute for Diabetes Research and Metabolic Diseases at Helmholtz Munich and at the University of Tübingen.
A drug commonly used to treat type 2 diabetes may reduce excess fluid in the brains of patients with hydrocephalus, which could help treat the disease less invasively than current treatments, according to a Northwestern Medicine study published in theJournal of Clinical Investigation.
Normal pressure hydrocephalus occurs when excess cerebrospinal fluid builds up inside the skull and puts pressure on the brain. The cause of the condition is elusive and affects up to three percent of individuals over the age of 65, with symptoms including cognitive decline, difficulty walking and bladder problems.
Patients are typically treated with permanent ventriculoperitoneal shunts, which are surgically implanted in the front or back of the skull and are connected to a valve that diverts excess cerebrospinal fluid away from the brain and into the abdomen where it is absorbed. The procedure has been shown to dramatically improve mobility, bladder control and cognitive functioning in patients with hydrocephalus, according to senior study author Stephen Magill, MD, PhD.
“It’s a great procedure because it’s one of the few things you can do that actually reverses these symptoms,” said Magill, who is assistant professor of Neurological Surgery.
There is, however, no pharmacological treatment currently approved to treat hydrocephalus. Additionally, nearly 20% of patients with normal pressure hydrocephalus also have type 2 diabetes and take sodium/glucose cotransporter 2 (SGLT2) inhibitors to manage their blood sugar, cardiovascular and kidney function, and weight loss.
Magill recently observed a reduction in the brain ventricle size in a patient with hydrocephalus who had a ventriculoperitoneal shunt surgically implanted and then began taking SGLT2 inhibitors to treat their type 2 diabetes. This phenomenon prompted Magill to further investigate the impact of SGLT2 inhibitors on ventricular size in patients with hydrocephalus.
“The medication inhibits a receptor found in the kidneys, which is where it works for diabetes. However, that receptor is also expressed in the choroid plexus, which is the structure in the brain that secretes the spinal fluid. Although this was known from animal studies, the clinical aspects of this biology have not been fully appreciated,” Magill said.
In the current study, three patients with hydrocephalus underwent CT scans both before and after surgery for ventriculoperitoneal shunts. After surgery, each patient began taking SGLT2 inhibitors for a medical indication and then underwent additional CT scans.
From analyzing these scans, Magill’s team discovered that all three patients showed a reduction in ventricle size as well as structural changes in their brains after starting SGLT2 therapy. One patient demonstrated dramatic ventricle size reduction due to ventricular collapse and required a shunt valve adjustment to reduce cerebrospinal fluid drainage.
“It’s a really interesting clinical observation because it raises the possibility that these medications could be used to treat normal pressure hydrocephalus in the future, which would normally require surgery,” Magill said.
Magill said the findings have sparked a new line of research in studying how SGLT2 inhibitors could help prevent hydrocephalus, adding that his team is now studying SGLT2 knockout mouse models to better understand the drug’s impact on ventricular size.
Their findings could ultimately inform new therapeutic strategies for treating normal pressure hydrocephalus as well as post-traumatic hydrocephalus, or the buildup of cerebrospinal fluid after traumatic brain injury, according to Magill.
“This sparks a new line of research on how normal pressured hydrocephalus develops, what causes it, how this protein works in creating and secreting spinal fluid, and has direct translational implications,” Magill said. “There’s a whole new avenue of potentially treating this disease that might save a patient from having surgery, and there’s always risks with surgery. It will also evolve our understanding of how these drugs work.”
