A new study in the European Heart Journal shows that people who develop type 1 diabetes in adulthood have an increased risk of cardiovascular disease and death, and that those diagnosed later in life do not have a better prognosis than those diagnosed earlier. The study, conducted by researchers at Karolinska Institutet, points to modifiable factors – smoking, poor glucose control and obesity – as the main risk factors.
Type 1 diabetes used to be called childhood diabetes but can start at any time during life – a situation for which there is limited research. The researchers behind the current study wanted to investigate the risk of cardiovascular disease and death in this group, particularly for those diagnosed after the age of 40.
The registry-based study identified 10 184 people diagnosed with type 1 diabetes in adulthood between 2001 and 2020 and compared them to 509 172 matched people in the control group.
The study shows that these people with adult-onset type 1 diabetes had a higher risk of cardiovascular disease and death from all causes, including cancer and infections, compared to the control group.
“The main reasons for the poor prognosis are smoking, overweight/obesity and poor glucose control. We found that they were less likely to use assistive devices, such as insulin pumps,” says first author Yuxia Wei, postdoctoral fellow at the Institute of Environmental Medicine, Karolinska Institutet.
The prognosis can be improved
The results emphasise the seriousness of type 1 diabetes, even when it starts later in life, the researchers say. But the prognosis can improved by avoiding smoking and obesity, especially for those diagnosed later in life.
The researchers plan to continue investigating adult-onset type 1 diabetes, including risk factors for developing the disease and the prognosis of other outcomes, such as microvascular complications. Optimal treatment in adult-onset type 1 diabetes, including the effect of pump use and other advanced technologies, also needs to be explored.
A study co-led by Indiana University School of Medicine researchers presents a potential new strategy to prevent or slow the progression of Type 1 diabetes by targeting an inflammation-related protein known to drive the disease. The findings, recently published in eBioMedicine, may help inform clinical trials of a drug that is already approved by the U.S. Food and Drug Administration for psoriasis as a treatment for Type 1 diabetes.
In laboratory studies using human cells and mouse models, the researchers found that applying a molecular method to block inflammation signalling through the tyrosine kinase 2 (TYK2) protein reduced harmful inflammation in the pancreas. This strategy not only protected the beta cells in the pancreas but also reduced the immune system’s attack on those cells. A medication that inhibits TYK2 is already approved for the treatment of psoriasis, an autoimmune condition that causes skin inflammation.
“Our study showed that targeting TYK2 could be a powerful way to protect insulin-producing beta cells while calming inflammation in the immune system at the same time,” said Carmella Evans-Molina, MD, PhD, co-author of the study and director of the Indiana Diabetes Research Center and the Eli Lilly and Company Professor of Pediatric Diabetes at the IU School of Medicine. “This finding is exciting because there is already a drug on the market that does this for psoriasis, which could help us move more quickly toward testing it for Type 1 diabetes.”
Past genetic studies have already shown that people with naturally lower TYK2 activity are less likely to develop Type 1 diabetes, further supporting the group’s approach for future treatments using this TYK2 inhibitor approach.
“Our preclinical models suggest that the treatment might work in people as well,” said Farooq Syed, PhD, lead author of the study and assistant professor in the Department of Diabetes-Immunology at the Arthur-Riggs Diabetes and Metabolic Research Institute of the City of Hope. “The next step is to initiate translational studies to evaluate the impact of TYK2 inhibition alone or in combination with other already approved drugs in individuals at-risk or with recent onset Type 1 diabetes.”
Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health
Exposure to antibiotics during a key developmental window in infancy can stunt the growth of insulin-producing cells in the pancreas and may boost risk of diabetes later in life, new research in mice suggests. The study, published this month in the journal Science, also pinpoints specific microorganisms that may help those critical cells proliferate in early life.
The findings are the latest to shine a light on the importance of the human infant microbiome—the constellation of bacteria and fungi living on and in us during our first few years. The research could lead to new approaches for addressing a host of metabolic diseases.
“We hope our study provides more awareness for how important the infant microbiome actually is for shaping development,” said first author Jennifer Hill, assistant professor in molecular, cellular and developmental biology at CU’s BioFrontiers Institute. “This work also provides important new evidence that microbe-based approaches could someday be used to not only prevent but also reverse diabetes.”
Something in the environment
More than 2 million U.S. adults live with Type 1 diabetes. The disease typically emerges in childhood, and genetics play a strong role. But scientists have found that, while identical twins share DNA that predisposes them to Type 1 diabetes, only one twin usually gets the disease.
“This tells you that there’s something about their environmental experiences that is changing their susceptibility,” said Hill.
For years, she has looked to microbes for answers.
Previous studies show that children who are breastfed or born vaginally, which can both promote a healthy infant microbiome, are less likely to develop Type 1 diabetes than others. Some research also shows that giving babies antibiotics early can inadvertently kill good bugs with bad and boost diabetes risk.
The lingering questions: What microbes are these infants missing out on?
“Our study identifies a critical window in early life when specific microbes are necessary to promote pancreatic cell development,” said Hill.
A key window of opportunity
She explained that human babies are born with a small amount of pancreatic “beta cells,” the only cells in the body that produce insulin. But some time in a baby’s first year, a once-in-a-lifetime surge in beta cell growth occurs.
“If, for whatever reason, we don’t undergo this event of expansion and proliferation, that can be a cause of diabetes,” Hill said.
She conducted the current study as a postdoctoral researcher at the University of Utah with senior author June Round, a professor of pathology.
They found that when they gave broad-spectrum antibiotics to mice during a specific window (the human equivalent of about 7 to 12 months of life), the mice developed fewer insulin producing cells, higher blood sugar levels, lower insulin levels and generally worse metabolic function in adulthood.
“This, to me, was shocking and a bit scary,” said Round. “It showed how important the microbiota is during this very short early period of development.”
Lessons in baby poop
In other experiments, the scientists gave specific microbes to mice, and found that several they increased their production of beta cells and boosted insulin levels in the blood. The most powerful was a fungus called Candida dubliniensis.
The team used faecal samples from The Environmental Determinants of Diabetes in the Young (TEDDY) study to make what Hill calls “poop slushies” and fed them to the mice.
When the researchers inoculated newborn mice with poop from healthy infants between 7 to 12 months in age, their beta cells began to grow. Poop from infants of other ages did not do the same. Notably, Candida dublineinsis was abundant in human babies only during this time period.
“This suggests that humans also have a narrow window of colonisation by these beta cell promoting microbes,” said Hill.
When male mice that were genetically predisposed to Type 1 diabetes were colonised with the fungus in infancy, they developed diabetes less than 15% of the time. Males that didn’t receive the fungus got diabetes 90% of the time.
Even more promising, when researchers gave the fungus to adult mice whose insulin-producing cells had been killed off, those cells regenerated.
Too early for treatments
Hill stresses that she is not “anti-antibiotics.” But she does imagine a day when doctors could give microbe-based drugs or supplements alongside antibiotics to replace the metabolism-supporting bugs they inadvertently kill.
Poop slushies (faecal microbiota transplants) have already been used experimentally to try to improve metabolic profiles of people with Type 2 diabetes, which can also damage pancreatic beta cells.
But such approaches can come with real risk, since many microbes that are beneficial in childhood can cause harm in adults. Instead, she hopes that scientists can someday harness the specific mechanisms the microbes use to develop novel treatments for healing a damaged pancreas—reversing diabetes.
She recently helped establish a state-of-the-art “germ-free” facility for studying the infant microbiome at CU Boulder. There, animals can be bred and raised entirely without microbes, and by re-introducing them one by one scientists can learn they work.
“Historically we have interpreted germs as something we want to avoid, but we probably have way more beneficial microbes than pathogens,” she said. “By harnessing their power, we can do a lot to benefit human health.”
People with type 1 diabetes require continuous insulin treatment and must regularly measure their glucose levels. With open-loop therapies*, insulin administration is manually controlled, while hybrid closed-loop systems* automatically regulate insulin delivery. A study with the involvement of the German Center for Diabetes Research showed that hybrid closed-loop systems offer improved long-term blood sugar values (HbA1c levels) and a lower risk of hypoglycaemic coma, but lead to a higher rate of diabetic ketoacidosis. The results were published in The Lancet Diabetes & Endocrinology.
Despite advances in insulin therapy, many people do not achieve their blood glucose targets and have a high risk of complications. Until now, the effect of insulin delivery in hybrid closed-loop systems on the risk of acute diabetes complications in people with type 1 diabetes has been unclear. Researchers have therefore now investigated whether the rates of severe hypoglycaemia and diabetic ketoacidosis are lower with hybrid closed-loop insulin therapy compared with sensor-augmented (open-loop) pump therapy.
Study with Nearly 14 000 Participants
In order to answer this question, the researchers, led by Professor Beate Karges, Faculty of Medicine at the RWTH Aachen, examined the data of nearly 14 000 participants. The study involved young people with type 1 diabetes from 250 diabetes centres in Germany, Austria, Switzerland, and Luxembourg. The participants were aged 2 to 20 years and had a type 1 diabetes duration of more than one year. They were identified from the Diabetes Prospective Follow-up Registry (DPV)**. The primary objectives of the study were to determine the rates of severe hypoglycaemia and ketoacidosis. Differences in HbA1c levels, time in the target range of 3.9 to 10.0mmol/L (70–180mg/dL), and fluctuations in blood sugar were also investigated. The data of 13 922 patients (51% male) were included in the analysis. Median age was 13.2 years; 7088 used a hybrid closed-loop system and 6834 used an open-loop system. The median observation time was 1.6 years.
Lower Rate of Hypoglycaemic Coma and More Ketoacidosis Events with Hybrid Closed-Loop Therapies
The results: People using hybrid closed-loop therapy had a significantly lower rate of rate of hypoglycaemic coma (0.62 per 100 patient-years) than those using open-loop therapy (0.91 per 100 patient-years). Furthermore, patients in the hybrid closed-loop group had a significantly lower HbA1c level (7.34% versus 7.50%). They had a higher percentage of time in the target glucose range of 3.9 to 10.0 mmol/L (64% versus 52% of the time). Their glycaemic variability was also lower (coefficient of variation of 35.4% versus 38.3%). There was no significant difference in the rate of severe hypoglycaemia.
However, individuals using a hybrid closed-loop system had a higher rate of ketoacidosis (1.74 events per 100 patient-years) than those using open-loop therapy (0.96 per 100 patient-years). The rate of ketoacidosis was particularly high in people with an HbA1c level of 8.5% or higher in the closed-loop therapy group (5.25 per 100 patient-years). In the comparison group, a rate of 1.53 events per 100 patient-years was observed.
Recommendation: Monitor Ketone Bodies Closely
Due to the higher risk of ketoacidosis, it is important to provide patients with targeted information and, in case of potential metabolic decompensation, to closely monitor ketone bodies in the blood or urine in order to prevent such adverse events, emphasize the authors of the study.
As global mobility surges, managing chronic conditions like diabetes during travel has become a significant concern. Diabetes remains one of the fastest-growing global public health issues1,affecting approximately 422 million people worldwide and causing 1.5 million deaths annually.2International SOS, the world’s leading health and security services company, has reported a significant year-on-year increase in diabetes-related assistance cases over the past three years, with a 28% increase in 2022 and a 32% increase in 2023.
Meanwhile, year-to-date 2024 data indicates a further uptick.3 With World Diabetes Day approaching on 14 November, organisations are urged to support diabetes prevention and management strategies. This year’s theme, ‘Breaking Barriers, Bridging Gaps’4 highlights the need for equitable, comprehensive and affordable diabetes care.
Dr Katherine O’Reilly, Regional Medical Director at International SOS, emphasises the importance of comprehensive health strategies: “It is important for organisations to understand the unique challenges that employees with diabetes face, particularly when travelling. By recognising these specific needs, companies can provide the necessary support and resources to help their employees manage their condition effectively. This ensures that employees can maintain their health and productivity, even when they are on the go. With thoughtful planning and the right resources, organisations can help their employees navigate the complexities of diabetes, fostering a supportive and inclusive work environment.”
People with diabetes face a double burden: a higher risk of life-threatening conditions like heart attack, stroke, and kidney failure, compounded by the psychological toll of diabetes distress. Individuals with diabetes are two to three times more likely to experience depression compared to those without the condition.5 These challenges can significantly impact employee wellbeing, leading to increased absenteeism, reduced productivity, and higher healthcare costs for employers.
According to The International Diabetes Federation (IDF), the global healthcare costs for individuals living with diabetes are expected to exceed $1054 billion by 2045.6 Furthermore, the prevalence of diabetes is projected to rise, with 643 million people affected by 2030, and 783 million by 2045.7 With this rising prevalence, it is crucial for organisations to implement strategies that help their workforce manage and prevent this chronic condition. Minor adjustments can reduce absenteeism, increase productivity, concentration and energy levels, and reduce the chance of on-the-job injury.
Dr Katherine O’Reilly continues, “Early diagnosis is crucial. Raising awareness about diabetes symptoms can prompt people to get screened, enabling early detection and intervention to prevent or delay its onset. This proactive approach can prevent undiagnosed diabetes from causing severe health complications, affecting various organ systems, including eye damage, heart and kidney disease, nerve damage and poor wound healing. By prioritising employee health, organisations can enhance productivity and foster a more engaged and resilient workforce. This approach also promotes a positive work environment and supports overall employee wellbeing.”
International SOS offers five tips for organisations to support employees in managing and preventing diabetes:
Education and awareness: Increase awareness about diabetes symptoms to encourage early diagnosis and effective management, thereby preventing severe health complications.
Provide comprehensive health solutions: Offer resources such as dietary guidelines, exercise programmes and regular health screenings to help employees manage their diabetes.
Supportive culture and policies: Develop and implement policies allowing for flexible work schedules and access to medical care while travelling. Foster a culture that prioritises health and wellbeing by accommodating regular meals and exercise, and ensuring employees have time to rest and recover from travel.
Promote a healthy lifestyle: Offer guidance on maintaining a healthy diet and regular exercise. Provide resources such as a list of healthy meal options and tips for finding nutritious food in different locations.
Facilitate health monitoring and provide adjustments: Ensure employees have scheduled breaks to take medication, check blood sugar levels and eat regular meals. Provide a private space for insulin administration and other medical needs.
A new paper surveying advances in diabetes pathogenesis and treatment explores the complex factors contributing to the onset and progression of the disease, suggesting that an understanding of these dynamics is key to developing targeted interventions to reduce the risk of developing diabetes and managing its complications.
In a paper in a special 50th anniversary issue of the peer-reviewed journal Cell, the authors surveyed hundreds of studies that have emerged over the years looking at the causes underpinning types 1 (T1D) and 2 (T2D) diabetes and new treatments for the disease. They examine the role that genes, environmental factors, and social determinants of health play and diabetes’ effect on cardiovascular and kidney disease.
What they found shows there are many advances in treatments that could stem the tide of a disease that has struck millions of people around the globe and continues to grow. In addition, some of these advances could be used to treat other disorders. But there are still challenges ahead.
“As the prevalence of diabetes continues to grow around the world, it is important to understand the latest advancements in research so that clinicians can provide the best care to their patients, and patients can make informed choices that support improved health outcomes,” said lead author Dr E. Dale Abel, chair of the UCLA Department of Medicine. “This is an educational resource that integrates the latest research and trends in diabetes management, which may have implications for clinical practice as the diabetic patient population continues to grow.
“This review will be the go-to reference for physicians and researchers, providing a state-of-the-art update of where the field is currently, and where it is headed,” Abel added.
Most people are affected by type 2 diabetes, for which inadequate diet and obesity are important underlying causes. Type 1 diabetes accounts for fewer than 5% of all cases. As of 2021 about 529 million people around the world were diagnosed with diabetes, representing about 6.1% of the global population, or about one in 16 people. Prevalence in some regions is as high as 12.3%. Type 2 diabetes comprises about 96% of cases, with more than half due to obesity. Some 1.31 billion people are projected to have the disease by 2050, with prevalence rising as high as 16.8% in North Africa and the Middle East and 11.3% in Latin America and the Caribbean, the researchers write.
Genetics, the central nervous system, and the interplay between various organs as well as social and environmental factors such as food insecurity and air pollution play a role in development of diabetes.
But some recent discoveries represent significant strides toward managing and perhaps even reversing the disease. For instance, a 2019 study found that a 14-day course of the antibody teplizumab delayed the progression of type 1 diabetes from stage 1 to stage 3 by 24 months. A follow-up analysis in 2021 showed that the delay could be up to 32.5 months.
Based on these results, the U.S. Food and Drug Administration approved teplizumab as the first disease-modifying therapy for type 1 diabetes, the researchers write.
Advances in insulins with optimised pharmacokinetics, algorithm-driven subcutaneous insulin pumps, continuous glucose monitoring, and improved tools for self-management have significantly improved the quality of life and outcomes for people with stage 3 type 1 diabetes.
In addition, stem cells could replace insulin-producing cells that are lost in type 1 diabetes, Abel said.
For type 2 diabetes, three classes of glucose-lowering medicines that were introduced in the last 20 years – GLP1RAs (glucagon like peptide-1 receptor agonists), DPP-4 inhibitors, and SGLT-2 inhibitors – have enabled people to control their glucose levels without gaining weight and with a low risk of developing hypoglycaemia. Personalised and precision medicine approaches are being explored to target the molecular mechanisms behind diabetes. However, they must demonstrate that benefits are clinically superior to standard care and are cost-effective. Also, it remains to be seen if precision approaches can be implemented in all settings worldwide, including those with few resources.
Combinations of GLP1Ras and with molecules that target other receptors such as GIP have shown even greater efficacy in treating diabetes. Recent trials have also shown that they are very effective in treating obesity, certain types of heart failure and even sleep apnoea, in part because of their potency to induce weight loss and reduce inflammation. Clinical trials are now underway to test their efficacy in treating other disorders such as Alzheimer’s disease, Abel said.
“Advances in therapy now raise the hope of preventing or curing T1D and treating T2D in ways that not only improve metabolic homeostasis, but also concretely reduce the risk and progression of cardio-renal disease,” the researchers write. “Finally, as we understand and develop tools for discerning the underlying heterogeneity leading to diabetes and its complications, the stage will be set for targeting therapies and prevention strategies to optimize their impact, in ways that will be broadly applicable across diverse populations and availability of health care resources.”
A 3D map of the islet density routes throughout the healthy human pancreas. Source: Wikimedia CC0
An experimental monoclonal antibody drug called mAb43 appears to prevent and reverse the onset of clinical type 1 diabetes in mice, in some cases lengthening the animals’ lifespan, report scientists at Johns Hopkins Medicine.
The drug is unique, according to the researchers, because it targets insulin-making beta cells in the pancreas directly and is designed to shield those cells from attacks by the body’s own immune system cells. The drug’s specificity for such cells may enable long-term use in humans with few side effects, say the researchers. Monoclonal antibodies are made by cloning, or making identical replicas of, an animal (including human) cell line.
The findings, published in Diabetes, raise the possibility of a new drug for type 1 diabetes, an autoimmune condition which has no cure or means of prevention. Unlike type 2 diabetes, in which the pancreas makes too little insulin, in type 1 diabetes, the pancreas makes no insulin because the immune system attacks the pancreatic cells that make it.
The lack of insulin interferes with the body’s ability to regulate blood sugar levels.
According to Dax Fu, PhD, associate professor of physiology at the Johns Hopkins University School of Medicine and leader of the research team, mAb43 binds to a small protein on the surface of beta cells, which dwell in clusters called islets. The drug was designed to provide a kind of shield or cloak to hide beta cells from immune system cells that attack them as “invaders.” The researchers used a mouse version of the monoclonal antibody, and will need to develop a humanised version for studies in people.
For the current study, the researchers gave 64 non-obese mice bred to develop type 1 diabetes a weekly dose of mAb43 via intravenous injection when they were 10 weeks old. After 35 weeks, all mice were non-diabetic. One of the mice developed diabetes for a period of time, but it recovered at 35 weeks, and that mouse had early signs of diabetes before the antibody was administered.
In five of the same type of diabetes-prone mice, the researchers held off giving weekly mAb43 doses until they were 14 weeks old, and then continued dosages and monitoring for up to 75 weeks. One of the five in the group developed diabetes, but no adverse events were found, say the researchers.
In the experiments in which mAb43 was given early on, the mice lived for the duration of the monitoring period of 75 weeks, compared with the control group of mice that did not receive the drug and lived about 18-40 weeks.
Next, the researchers, including postdoctoral fellows Devi Kasinathan and Zheng Guo, looked more closely at the mice that received mAb43 and used a biological marker called Ki67 to see if beta cells were multiplying in the pancreas. They said, after treatment with the antibody, immune cells retreated from beta cells, reducing the amount of inflammation in the area. In addition, beta cells slowly began reproducing.
“mAb43 in combination with insulin therapy may have the potential to gradually reduce insulin use while beta cells regenerate, ultimately eliminating the need to use insulin supplementation for glycaemic control,” says Kasinathan.
The research team found that mAb43 specifically bound to beta cells, which make up about 1% or 2% of pancreas cells.
Another monoclonal antibody drug, teplizumab, received US Food and Drug Administration approval in 2022. Teplizumab binds to T cells, making them less harmful to insulin-producing beta cells. The drug has been shown to delay the onset of clinical (stage 3) type 1 diabetes by about two years, giving young children who get the disease time to mature and learn to manage lifelong insulin injections and dietary restrictions.
“It’s possible that mAb43 could be used for longer than teplizumab and delay diabetes onset for a much longer time, potentially for as long as it’s administered,” says Fu.
A new Cochrane review has found that insulin can be kept at room temperature for months without losing potency, offering hope to people living with diabetes in regions with limited access to healthcare or stable powered refrigeration. This affects millions of people living in low- and middle-income countries, particularly in rural areas, as well as people whose lives have been disrupted by conflict or natural disasters.
Insulin is an essential medicine for people with diabetes and current guidance states that before use it must be kept refrigerated to preserve its effectiveness. For millions of people with diabetes living in low- and middle-income countries, however, the harsh reality is that electricity and refrigeration are luxuries that are unavailable to them. Vulnerable populations in war-torn areas, disaster-prone regions, and climate crisis-affected areas, including those enduring extreme heat, also need solutions that don’t rely on powered fridges.
The new Cochrane review summarises results of different studies investigating what happens to insulin when stored outside of fridges, including previously unpublished data from manufacturers. The review found that it is possible to store unopened vials and cartridges of specific types of human insulin at temperatures of up to 25°C for a maximum of six months, and up to 37°C for a maximum of two months, without any clinically relevant loss of insulin activity. Data from one study showed no loss of insulin activity for specific insulin types when stored in oscillating ambient temperatures of between 25°C and 37°C for up to three months. This fluctuation resembles the day-night temperature cycles experienced in tropical countries.
The research team, led by Bernd Richter from the Institute of General Practice, Medical Faculty of the Heinrich-Heine-University in Düsseldorf, Germany, conducted comprehensive research to investigate insulin stability under various storage conditions. The review analysed a total of seventeen studies, including laboratory investigations of insulin vials, cartridges/pens, and prefilled syringes, demonstrating consistent insulin potency at temperatures ranging from 4°C to 37°C, with no clinically relevant loss of insulin activity.
Bernd stressed the significance of this research, particularly for people living with type 1 diabetes, where “insulin is a lifeline, as their very lives depend on it. While type 2 diabetes presents its challenges, type 1 diabetes necessitates insulin for survival. This underscores the critical need for clear guidance for people with diabetes in critical life situations, which many individuals lack from official sources.
“Our study opens up new possibilities for individuals living in challenging environments, where access to refrigeration is limited. By understanding the thermal stability of insulin and exploring innovative storage solutions, we can make a significant impact on the lives of those who depend on insulin for their well-being.”
These findings can help communities facing challenges in securing constant cold storage of insulin. They provide reassurance that alternatives to powered refrigeration of insulin are possible without compromising the stability of this essential medicine. It suggests that if reliable refrigeration is not possible, room temperature can be lowered using simple cooling devices such as clay pots for insulin storage.
The researchers have also identified uncertainties for future research to address. There remains a need to better understand insulin effectiveness following storage under varying conditions. Further research is also needed on mixed insulin, influence of motion for example when insulin pumps are used, contamination in opened vials and cartridges, and studies on cold environmental conditions.
A new study appearing in Cell Medicine Reports suggests that an existing drug could be repurposed to treat type 1 diabetes, potentially reducing dependence on insulin as the sole treatment.
Type 1 diabetes, an autoimmune disease which attacks insulin-producing beta cells in the pancreas, is traditionally managed by replacing the missing insulin with injections which, though effective, can be expensive and burdensome.
The research, led by researchers at the University of Chicago Medicine and Indiana University, focuses on α-difluoromethylornithine (DFMO), which inhibits an enzyme that plays a key role in cellular metabolism. The latest translational results are a culmination of years of research: In 2010, while corresponding author Raghu Mirmira, MD, PhD, was at Indiana University, he and his lab performed fundamental biochemistry experiments on beta cells in culture. They found that suppressing the metabolic pathway altered by DFMO helped protect the beta cells from environmental factors, hinting at the possibility of preserving and even restoring these vital cells in patients diagnosed with type 1 diabetes.
The researchers confirmed their observations preclinically in zebrafish and then in mice before senior author Linda DiMeglio, MD, MPH, Edwin Letzter Professor of Pediatrics at Indiana University School of Medicine and a pediatric endocrinologist at Riley Children’s Health, launched a clinical trial to evaluate the safety and tolerability of the drug in type 1 diabetes patients. The results of the trial, which was funded by the Juvenile Diabetes Research Foundation (JDRF) and used DMFO provided by Panbela Therapeutics, indicated that the drug is safe for type 1 diabetes patients and can help keep insulin levels stable by protecting beta cells.
“As a physician-scientist, this is the kind of thing we’ve always strived for – to discover something at a very basic, fundamental level in cells and find a way to bring it into the clinic,” said Mirmira, who is now Professor of Medicine and an endocrinologist at UChicago Medicine. “It definitely underscores the importance of supporting basic science research.”
“It’s been truly thrilling to witness the promising results in the pilot trial after this long journey, and we’re excited to continue our meaningful collaboration,” said DiMeglio.
Importantly, DFMO has already been FDA-approved as a high dose injection since 1990 for treating African Sleeping Sickness and received breakthrough therapy designation for neuroblastoma maintenance therapy after remission in 2020. Pre-existing regulatory approval could potentially facilitate its use in type 1 diabetes, saving effort and expense and getting the treatment to patients sooner.
“For a drug that’s already approved for other indications, the approval timeline can be a matter of years instead of decades once you have solid clinical evidence for safety and efficacy,” said Mirmira. “Using a new formulation of DFMO as a pill allows patients to take it by mouth instead of needing to undergo regular injections, and it has a very favorable side effect profile. It’s exciting to say we have a drug that works differently from every other treatment we have for this disease.”
To follow up on the recently published results, a multi-centre clinical trial was launched to gather even stronger data regarding the efficacy of DFMO as a type 1 diabetes treatment.
“With our promising early findings, we hold hope that DFMO, possibly as part of a combination therapy, could offer potential benefits to preserve insulin secretion in individuals with recent-onset type 1 diabetes and ultimately also be tested in those who are at risk of developing the condition,” said Sims.
“A new era is dawning where we’re thinking of novel ways to modify the disease using different types of drugs and targets that we didn’t classically think of in type 1 diabetes treatment,” said Mirmira.
Treating newly diagnosed Type 1 diabetes patients with semaglutide may drastically reduce or even eliminate their need for injected insulin, according to the remarkable findings of a small University at Buffalo study reported in the New England Journal of Medicine.
“Our findings from this admittedly small study are, nevertheless, so promising for newly diagnosed Type 1 diabetes patients that we are now absolutely focused on pursuing a larger study for a longer period of time,” says Paresh Dandona, MD, PhD, professor and senior author on the paper.
A total of 10 patients at UB’s Clinical Research Center in the Division of Endocrinology were studied from 2020 to 2022, all of whom had been diagnosed in the past three to six months with Type 1 diabetes. The mean HbA1c level over 90 days at diagnosis was 11.7, far above the American Diabetes Association’s HbA1c recommendation of 7 or below.
The patients were treated first with a low dose of semaglutide while also taking meal-time (bolus) insulin and basal (background) insulin. As the study continued, semaglutide dosing was increased while mealtime insulin was reduced in order to avoid hypoglycaemia.
“Within three months, we were able to eliminate all of the mealtime insulin doses for all of the patients,” says Dandona, “and within six months we were able to eliminate basal insulin in 7 of the 10 patients. This was maintained until the end of the 12-month follow-up period.”
During that time, the patients’ mean HbA1c fell to 5.9 at six months and 5.7 at 12 months.
Applying Type 2 diabetes drugs to treat Type 1 diabetes
For more than a decade, Dandona has been interested in how drugs developed for Type 2 diabetes might be utilized in treating Type 1 diabetes as well.
He and his colleagues were the first to study how liraglutide, another drug for Type 2 diabetes, might work in patients with Type 1 diabetes in a study he published in 2011.
“As we extended this work, we found that a significant proportion of such diabetics still have some insulin reserve in the beta cells of their pancreas,” Dandona explains. “This reserve is most impressive at the time of diagnosis, when 50% of the capacity is still present. This allowed us to hypothesise that semaglutide, which works through stimulation of insulin secretion from the beta cell, could potentially replace mealtime insulin administration.”
From the outset, the goal of the current study was to see if semaglutide treatment could be used to replace mealtime insulin, thereby reducing the insulin dosage, improving glycaemic control, reducing the HbA1c and eliminating potentially dangerous swings in blood sugar and hypoglycaemia.
The most common side effects for patients were nausea and vomiting as well as appetite suppression, which led a number of patients to experience weight loss, an outcome that Dandona says is generally an advantage since 50% of patients with Type 1 diabetes in the US are overweight or obese.
“As we proceeded with the study, we found that even the dose of basal insulin could be reduced or eliminated altogether in a majority of these patients,” he says. “We were definitely surprised by our findings and also quite excited. If these findings are borne out in larger studies over extended follow-up periods, it could possibly be the most dramatic change in treating Type 1 diabetes since the discovery of insulin in 1921.”
