Body appreciation levels are associated with internalisation of thin ideals and with sociocultural pressure, which vary by culture and age
Photo by I Yunmai on Unsplash
People from different cultures show both similarities and differences in how body appreciation, sociocultural pressure, and internalisation of thin ideals vary, according to a study published July 31, 2024 in the open-access journal PLOS ONEby Louise Hanson from Durham University, UK, and colleagues.
Body image is a multifaceted and complex phenomenon encapsulating how we think, behave, and feel about our body. To date, most body image research has focused on young, White, Western women, and has focused on negative rather than positive body image.
By contrast, Hanson and colleagues examined body appreciation, encapsulating positive thoughts and feelings regarding one’s own body. They also included participants not only from Western countries (ie, Australia, Canada, United Kingdom, United States of America), but also China and Nigeria. A final sample of 1186 women completed the questionnaires and were included in the analysis.
The results did not reveal significant difference in body satisfaction between women of different ages, but there was significant variation between cultures. Black Nigerian women had the highest body appreciation, followed by Eastern Asian Chinese women, with White Western women reporting lowest body appreciation. The findings suggest that ethnicity and culture are important influences on body appreciation and might act as protective factors that promote positive body image.
High internalisation of the thin ideal, and high perceived pressure about appearance from family, peers, and the media, were associated with lower body appreciation. Internalisation varied by age in some cultures: older White Western and Black Nigerian women reported lower thin-ideal internalisation than younger women, but Chinese women experienced the same thin-ideal internalisation across the lifespan.
For women from all cultures, older women reported lower perceived sociocultural pressure than younger women. White Western women experienced more perceived pressure from the media than Black Nigerian and Chinese women, but Chinese women reported the most pressure from peers. The results also showed that Black Nigerian women reported the lowest sociocultural pressure overall, and that Chinese women reported the most pressure.
The authors suggest that future studies should include more women in older age groups to obtain a fully representative picture of women’s body appreciation across the lifespan. In addition, further development of measurement tools is necessary for future research in cross-cultural contexts. According to the authors, the results of the current study could be used to target positive body image interventions to each culture. Further research may be required to develop effective interventions for each group.
The authors add: “We found that body appreciation was relatively stable across all ages and sociocultural pressure was evident in all cultures. However, the extent to which this pressure was experienced and where it came from differed across cultures.”
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.”
Researchers at UCLA Health uncovered new information about the role inflammation plays in mitigating liver fibrosis, which is associated with metabolic-associated fatty liver disease (MAFLD). While inflammation in the liver has long been considered a prerequisite to developing liver fibrosis, the scarring and thickening of tissue that can impair the liver’s ability to function, this new research, published in the Journal of Clinical Investigation, suggests that reducing inflammation may not influence the extent of fibrosis.
“Liver fibrosis is the critical feature that creates chronic liver disease and liver cancer. If we can keep fibrosis in check then we can meaningfully impact liver disease,” said Tamer Sallam, MD, corresponding author of the study and vice chair and associate professor in the department of medicine at the David Geffen School of Medicine at UCLA.
“For decades we have believed that targeting inflammation is one of the most important ways to reduce MAFLD. But this new research indicates that inflammation, while still important, may not be the main driver of fibrosis.”
The studylooked specifically at a protein called lipopolysaccharide binding protein (LBP), which is involved in the body’s immune response, and how LBP functions in mice. Findings showed that mice without LBP in their liver cells had lower levels of liver inflammation and better liver function but no change in fibrosis.
In addition to mouse models, the researchers also studied genetic analyses from large human datasets and human tissue samples from MAFLD patients at different stages in the disease, to examine the consequence of loss of LBP function. The evidence combined showed that the LBP does not alter scar tissue markers.
Sallam indicated a need to further explore how LBP influences inflammation and whether other factors can offer a more potent reduction in inflammation and have an impact on reducing fibrosis.
“Reducing scar burden is one of the holy grails in the treatment of advanced liver diseases,” Sallam said. “These results suggest that certain ways of targeting inflammation may not be a viable option and that more directed therapies against other pathways could help us better target fibrosis and improve outcomes for patients.”
High-protein diets, known as ‘‘Paleolithic diets’’, are popular. Using mouse models, scientists at the University of Geneva (UNIGE) have studied their impact. While effective in regulating weight and stabilizing diabetes, these diets are not without risks. Excess protein greatly increases ammonium production, overwhelming the liver. Excess ammonium can cause neurological disorders and, in severe cases, lead to coma. These results, published in the Journal of Biological Chemistry, suggest caution when following these diets.
While current treatments help control the progression of the type 2 diabetes, they do not cure it. Losing weight is often an essential part of the treatment.
‘‘Diets rich in animal and/or plant proteins, known as Paleolithic diets, can be used to stabilise type 2 diabetes and regulate weight,’’ explains Pierre Maechler, full professor at the Department of Cell Physiology and Metabolism at the UNIGE Faculty of Medicine, who led this research. These diets are inspired by the meat-based diets of pre-agricultural time. ‘‘But what impact do they have on the body? Are they harmless? That’s what we set out to find out.’’
Liver under Pressure
Ammonium is a normal waste product of protein breakdown, essentially eliminated in the liver by the enzyme glutamate dehydrogenase (GDH). In the event of protein overload, the GDH enzyme comes under pressure. To study the impact of high-protein diets, Pierre Maechler’s team fed healthy mice and mice lacking the GDH enzyme in their liver a diet with a protein content mimicking the so-called Paleolithic diet.
Scientists observed that in healthy mice, although excess protein increased ammonium production, the liver managed this excess due to the action of the GDH enzyme, which detoxifies ammonium before it can cause damage. ‘‘In contrast, in mice lacking the GDH enzyme, the liver is unable to eliminate the excess of toxic ammonium derived from proteins. No need to wait for weeks or months; a change of diet lasting a few days is enough to observe major consequences,’’ explains Karolina Luczkowska, a former PhD student at the Department of Cell Physiology and Metabolism at the UNIGE Faculty of Medicine, and the study’s first author.
Caution is Advised
These results suggest that in case of dysfunctional GDH enzyme, high-protein diets may cause a harmful excess of ammonium. Ammonium not eliminated by the liver can cause severe disorders, particularly neurological ones. A blood test could assess GDH activity to avoid overloading the metabolism with proteins in people whose GDH enzyme is deficient. ‘‘It is therefore important to be well informed before following a high-protein diet,’’ concludes Pierre Maechler.
By modulating a network of proteins found in the central nervous system, the effectiveness and reduce the side effects of glucagon-like peptide (GLP)-1 agonists.
The study, published in the Journal of Clinical Investigation, focused on two proteins called melanocortin 3 and melanocortin 4 found primarily on the surface of neurons in the brain that play a central role in regulating feeding behaviour and maintaining the body’s energy balance.
Melanocortin 3 and melanocortin 4 impact everything from sensing long-term energy stores to processing signals from the gut regarding short-term fullness, or satiety, said U-M physiologist Roger Cone, who led the study.
The GLP-1 agonist class, which includes semaglutides and tirzepatides, has received substantial attention recently for their effectiveness in treating not only type 2 diabetes, but also obesity, heart disease and potentially addiction. They work by mimicking a natural satiation hormone, triggering the brain to reduce feeding behaviour.
“So the obvious question for us was: How do these GLP-1 drugs, which work by manipulating satiety signals, function when we prime the melanocortin system?” said Cone, professor of molecular and integrative physiology at the U-M Medical School and director of the U-M Life Sciences Institute where his lab is located.
Working in mouse models, Cone and his colleagues tested the effects of several hormones that reduce food intake. They compared the results in normal mice with mice that genetically lacked the MC3R protein, in mice that were given chemicals to block the activity of MC3R, and in mice that were given a drug to increase the activity of MC4R. (Because MC3R is a natural negative regulator of MC4R, meaning it decreases the activity of MC4R, blocking MC3R and increasing MC4R activity has similar effects.)
In all cases, Naima Dahir, first author of the study and a postdoctoral research fellow in Cone’s lab, and colleagues found that adjusting the melanocortin system – either by inhibiting MC3R or increasing MC4R activity – made the mice more sensitive to GLP-1 drugs and other hormones that affect feeding behaviour. The mice that were given a GLP-1 drug in combination with an MC4R agonist or MC3R antagonist showed up to five times more weight loss and reduced feeding than mice receiving only the GLP-1 drugs.
“We found that activating the central melanocortin system hypersensitises animals to the effects of not just GLP-1s, but to every anti-feeding hormone we tested,” Cone said.
The researchers also measured activity in parts of the brain thought to trigger nausea in response to GLP-1 drugs and observed no increased activation when GLP-1 drugs were combined with alterations to the melanocortin system. In contrast, priming of the melanocortin neurons significantly increased GLP-1 drug activation of neurons in hypothalamic feeding centres in the brain.
The findings indicate that pairing the existing GLP-1 drugs with an MC4R agonist could increase sensitivity to the desired effects of the drugs by up to fivefold, without increasing unwanted side effects. Ultimately, this approach could enable patients who are sensitive to the side effects to take a lower dose, or could improve the results in patients who have not responded to the existing drug dosages. Further drug development and clinical testing are needed before this can occur.
While this research has been conducted only in mouse models, Cone is optimistic that the results will translate well to humans.
“The melanocortin system is highly conserved in humans,” he said. “Everything we’ve observed in the mouse over the past decades studying these proteins has also been found in humans, so I suspect that these results would also be translatable to patients.”
Photoreceptor cells in the retina. Credit: Scientific Animations
Researchers from Mass Eye and Ear have discovered an association between semaglutide use and an increased risk of nonarteritic anterior ischaemic optic neuropathy (NAION) in patients with type 2 diabetes, overweight or obesity. The findings, which appear in JAMA Ophthalmology, only show an association and cannot establish causation.
Though NAION is relatively rare, occurring in in about 10 in 100 000, it is the second most common cause of optic nerve blindness, behind glaucoma, and it is the most common cause of sudden optic nerve blindness. Caused by decreased blood flow to the optic disc, it usually affects only one eye but in 15% of cases both eyes are involved. There are no treatments for this disease and little prospect for improvement, although it is painless.
The study was led by Joseph Rizzo, MD, director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the Simmons Lessell Professor of Ophthalmology at Harvard Medical School.
In mid-2023 Rizzo, a resident (study co-author Seyedeh Maryam Zekavat, MD, PhD) and other Mass Eye and Ear neuro-ophthalmologists noticed a disturbing trend – three patients in their practice had been diagnosed with vision loss from this relatively uncommon optic nerve disease in just one week. They did notice however that all three were taking semaglutide.
“The use of these drugs has exploded throughout industrialised countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” said Rizzo, corresponding author of the study. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.”
This prompted the Mass Eye and Ear research team to run a retrospective analysis of their patient population to see if they could identify a link between this disease and these drugs.
They performed matched cohort study of 16 827 patients revealed higher risk of NAION in patients prescribed semaglutide compared with patients prescribed non–GLP-1 receptor agonist medications for diabetes or obesity.
The researchers found that patients with diabetes who were prescribed and took semaglutide were four times (hazard ratio [HR], 4.28) more likely to be receive a NAION diagnosis. The odds increased to more than seven times (HR, 7.64) when the prescription was for weight control in obesity.
The researchers analysed the records of more than 17 000 Mass Eye and Ear patients treated over the six years since Ozempic was released and divided the patients in those who were diagnosed with either diabetes or overweight/ obesity. The researchers compared patients who had received prescriptions for semaglutide compared to those taking other diabetes or weight loss drugs. Then, they analysed the rate of NAION diagnoses in the groups, which revealed the significant risk increases.
Study limitations include the fact that Mass Eye and Ear sees an unusually high number of people with rare eye diseases, and the number of NAION cases seen over the six-year study period is relatively small. With small case numbers, statistics can change quickly, Rizzo noted. Medication adherence could also not be assessed.
Only correlation can be shown by the study, not causality. How or why this association exists remains unknown. Likewise, the reason for the reported difference between diabetic and overweight groups – but this does not appear to result from a difference in baseline characteristics. The optic nerve is known to host GLP-1 receptors, but the study did not adequately address all the confounding factors. They also caution against generalising the results (from a majority white population) since Black individuals have a lower risk of NAION.
“Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population,” Rizzo said. “This is information we did not have before and it should be included in discussions between patients and their doctors, especially if patients have other known optic nerve problems like glaucoma or if there is pre-existing significant visual loss from other causes.”
Maintaining prediabetic status after diagnosis reduces risk of death decades later
Individuals diagnosed with prediabetes can reduce their long-term risk of death and diabetes-related health complications if they delay the onset of diabetes for just four years through diet and exercise. Guangwei Li of the China-Japan Friendship Hospital and colleagues report these findings in a new study published July 9thin the open-access journal PLOS Medicine.
Type 2 diabetes is associated with an increased risk of death and disability, and imposes a significant economic burden on individuals and societies worldwide. Lifestyle changes, such as eating a healthy diet and getting more exercise, can delay or reduce the risk of developing diabetes in people diagnosed with impaired glucose tolerance – commonly called prediabetes. However, it is unknown how long a person must delay diabetes to ensure better long-term health.
In the new study, researchers looked at health outcomes from 540 prediabetic individuals who participated in the original Da Qing Diabetes Prevention Study, a six-year trial conducted in Da Qing City in China, starting in 1986. Participants belonged to either a control group or one of three lifestyle intervention groups, which involved following a healthy diet, getting more exercise, or both. The trial followed up with participants for more than 30 years.
Li’s team determined the long-term risk of death, cardiovascular events – like heart attack, stroke or heart failure – and other diabetes-related complications for trial participants. They found that individuals who remained non-diabetic for at least four years after their initial diagnosis had a significantly lower risk of dying and a significantly lower risk of experiencing a cardiovascular event compared to those who developed diabetes sooner. This protective effect was not observed in individuals who remained non-diabetic for less than the “four-year threshold.”
Overall, the analysis suggests that the longer a prediabetic person can delay developing diabetes, the better their long-term health outcomes will be. However, even just a few years of maintaining prediabetic status can yield benefits for years to come.
The authors add, “This study suggests that a longer duration of non-diabetes status in those with IGT has beneficial health outcomes and reduces mortality. The implementation of effective interventions targeting those with IGT should be considered as part of preventative management for diabetes and diabetes related vascular complications.”
People with prediabetes are advised to reduce their weight in order to prevent the development of diabetes. For the first time, new research shows that people achieve the best diabetes protection when they reduce their weight and at the same time normalise blood sugar regulation with lifestyle changes and medication. In an article published in Diabetologia, the authors argue that the normalisation of blood sugar levels in prediabetes should be included as a therapeutic goal in the guidelines in order to improve the prevention of type 2 diabetes.
Diabetes is widespread and is associated with an increased risk of a number of life-threatening complications such as stroke, heart attack and kidney failure. “In order to prevent the development of the disease, early therapies are already important in the prediabetes stage, a preliminary stage of type 2 diabetes. Our results can be used to change the goals of these early lifestyle interventions in order to reduce the overall development rates of diabetes,” explains first author Reiner Jumpertz-von Schwartzenberg.
Prediabetes drastically increases the risk of diabetes
Prediabetes is diagnosed when there is no manifest type 2 diabetes yet, but the fasting blood sugar is already elevated and glucose tolerance is impaired. To prevent prediabetes from becoming diabetes, affected patients are advised to reduce their weight. US guidelines from the American Diabetes Association (ADA), for example, recommend reducing body weight by at least 7%. This recommendation is based on the DPP study.
The research team from the University Tübingen and the National Institute of Diabetes and Digestive and Kidney Diseases in the US, investigated whether this weight loss is sufficient, or whether it is not better to prevent diabetes by also reducing blood sugar levels such that prediabetes goes into remission.
Prevention through one-year lifestyle intervention
They analysed data from 480 people with prediabetes who participated in the US Diabetes Prevention Program (DPP) and had lost at least 7% of their body weight through a one-year lifestyle intervention. In 114 of them, prediabetes also went into remission during the intervention, meaning that their fasting blood sugar, glucose tolerance and HbA1c had normalised. However, the majority of the 366 study participants had not managed to significantly improve their blood sugar regulation despite successfully losing weight. Their prediabetes was not in remission at the end of the intervention.
The researchers found that significantly fewer people in the group that had lost weight and achieved prediabetes remission developed manifest diabetes thereafter. The additional remission of prediabetes resulted in a relative risk reduction for the development of diabetes of 76% compared to those who had not achieved normalisation of their blood sugar levels. The absolute risk reduction was higher than 10%.
“In the group with additional remission of prediabetes, there was even no type 2 diabetes at all in the first 4 years after the lifestyle intervention,” reports last author Andreas Birkenfeld. “In the group that had ‘only’ lost weight, however, some study participants did develop manifest diabetes during that period.”
Jumpertz-von Schwartzenberg and Birkenfeld draw a clear conclusion: “Our results show that remission of prediabetes brings a further significant benefit in addition to weight reduction. We therefore advocate that the goal of prediabetes remission should be included in the objectives of the practice guidelines in order to significantly improve the prevention of type 2 diabetes.”
The study was conducted by researchers from the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the University of Tübingen, a partner in the German Center for Diabetes Research (DZD), together with US colleagues in the renowned “Diabetes Prevention Program (DPP)”.
In an international phase III study, researchers have demonstrated the potential of tirzepatide, known to manage type 2 diabetes, as the first effective drug therapy for obstructive sleep apnoea (OSA), a sleep-related disorder characterised by repeated episodes of irregular breathing due to complete or partial blockage of the upper airway.
The results, published in the New England Journal of Medicine, highlight the treatment’s potential to improve the quality of life for millions around the world affected by OSA.
“This study marks a significant milestone in the treatment of OSA, offering a promising new therapeutic option that addresses both respiratory and metabolic complications,” said Atul Malhotra, MD, lead author of the study, professor of medicine at University of California San Diego School of Medicine and director of sleep medicine at UC San Diego Health.
OSA can result in reduced blood oxygen levels and can also be associated with an increased risk of cardiovascular complications, such as hypertension and heart disease. Recent studies, also led by Malhotra, suggest that the number of OSA patients worldwide is close to 936 million.
Conducted in two Phase III, double-blinded, randomised, controlled trials, the new study cohort recruited 469 participants from 9 countries with clinical obesity and living with moderate-to-severe OSA. Participants either used or did not use continuous positive airway pressure (CPAP) therapy, the most common sleep apnoea treatment which uses a machine to maintain an open airway during sleep, preventing interruptions in breathing. Patients were administered either 10 or 15mg of the drug by injection or a placebo and followed for 52 weeks.
Researchers found that tirzepatide led to a significant decrease in the number of breathing interruptions during sleep, a key indicator used to measure the severity of OSA. This improvement was much greater than what was seen in participants that were given a placebo. Importantly, some participants that took the drug reached a point where CPAP therapy might not be necessary. Considerable data suggest that a drug therapy that targets both sleep apnoea and obesity is beneficial rather than treating either condition alone.
Additionally, the drug therapy improved other aspects related to OSA, such as reducing the risk factors of cardiovascular diseases and improved body weight. The most common side effect reported was mild stomach issues.
“Historically, treating OSA meant using devices during sleep, like a CPAP machine, to alleviate breathing difficulties and symptoms,” Malhotra said. “However, its effectiveness relies on consistent use. This new drug treatment offers a more accessible alternative for individuals who cannot tolerate or adhere to existing therapies. We believe that the combination of CPAP therapy with weight loss will be optimal for improving cardiometabolic risk and symptoms. Tirzepatide can also target specific underlying mechanisms of sleep apnoea, potentially leading to more personalised and effective treatment.”
Malhotra adds that having a drug therapy for OSA represents a significant advancement in the field.
“It means we can offer an innovative solution, signifying hope and a new standard of care to provide relief to countless individuals and their families who have struggled with the limitations of existing treatments,” said Malhotra. “This breakthrough opens the door to a new era of OSA management for people diagnosed with obesity, potentially transforming how we approach and treat this pervasive condition on a global scale.”
Next steps include conducting clinical trials to examine longer term effects of tirzepatide.
A 3D map of the islet density routes throughout the healthy human pancreas. Source: Wikimedia CC0
Northwestern University researchers have developed a new antioxidant biomaterial that someday could provide much-needed relief to people living with chronic pancreatitis. The study was published in the journal Science Advances.
Before surgeons remove the pancreas from patients with severe, painful chronic pancreatitis, they first harvest insulin-producing tissue clusters, called islets, and transplant them into the vasculature of the liver. The goal of the transplant is to preserve a patient’s ability to control their own blood-glucose levels without insulin injections.
Unfortunately, the process inadvertently destroys 50–80% of islets, and one-third of patients become diabetic after surgery. Three years post-surgery, 70% of patients require insulin injections, which are accompanied by a list of side effects, including weight gain, hypoglycaemia and fatigue.
In the new study, researchers transplanted islets from the pancreas to the omentum – the large, flat, fatty tissue that covers the intestines – instead of the liver. And, to create a healthier microenvironment for the islets, the researchers adhered the islets to the omentum with an inherently antioxidant and anti-inflammatory biomaterial, which rapidly transforms from a liquid to a gel when exposed to body temperature.
In studies with mouse and non-human primates, the gel successfully prevented oxidative stress and inflammatory reactions, significantly improving survival and preserving function of transplanted islets. It marks the first time a synthetic antioxidant gel has been used to preserve function of transplanted islets.
“Although islet transplantation has improved over the years, long-term outcomes remain poor,” said Northwestern’s Guillermo A. Ameer, who led the study. “There is clearly a need for alternative solutions. We have engineered a cutting-edge synthetic material that provides a supportive microenvironment for islet function. When tested in animals, we were successful. It kept islet function maximised and restored normal blood sugar levels. We also report a reduction in units of insulin that animals required.”
“With this new approach, we hope that patients will no longer have to choose between living with the physical pain of chronic pancreatitis or the complications of diabetes,” added Jacqueline Burke, a research assistant professor of biomedical engineering at Northwestern and the paper’s first author.
‘Compromised quality of life’
For patients living without a pancreas, side effects such as managing blood-sugar levels can be a lifelong struggle. By secreting insulin in response to glucose, islets help the body maintain glycaemic control. Without functioning islets, people must closely monitor their blood-sugar levels and frequently inject insulin.
“Living without functional islets places a great burden on patients,” Burke said. “They must learn to count carbs, dose insulin at the appropriate time and continuously monitor blood glucose. This consumes much of their time and mental energy. Even with great care, exogeneous insulin therapy is not as effective as islets for maintaining glucose control.”
“It’s a compromised quality of life,” Ameer said. “Instead of multiple insulin injections, we would love to collect and preserve as many islets as possible.”
But, unfortunately, the current standard of care for preserving islets often leads to poor outcomes. After the surgery to remove the pancreas, surgeons isolate islets from the pancreas and transplant them to the liver through portal vein infusion. This intraportal perfusion procedure has several common complications. Islets in direct contact with blood flow undergo an inflammatory response, more than half of the islets die, and transplanted islets can cause dangerous clots in the liver. For those reasons, physicians and researchers have been searching for an alternate transplantation site.
In previous clinical studies, researchers transplanted islets to the omentum instead of the liver in order to bypass issues with clotting. To secure the islets on the omentum, physicians used plasma from the patients’ own blood to form a biologic gel. While the omentum appeared to work better than the liver as a transplantation site, several issues, including clots and inflammation, remained.
“There’s been significant interest in the research and medical communities to find an alternate islet transplantation site,” Ameer said. “The results from the omentum study were encouraging, but outcomes were varied. We believe that’s because the use of the patients’ blood and the added components required to create the biologic gel can affect reproducibility among patients.”
A citrate solution
To protect the islets and improve outcomes, Ameer turned to the citrate-based biomaterials platform with inherent antioxidant properties developed in his laboratory. Used in products approved by U.S. Food and Drug Administration for musculoskeletal surgeries, citrate-based biomaterials have demonstrated the ability to control the body’s inflammatory responses. Ameer set out to investigate whether a version of these biomaterials with biodegradable and temperature-responsive phase-changing properties would provide a superior alternative to a biologic gel obtained from blood.
In cell cultures, both mouse and human islets stored within the citrate-based gel maintained viability much longer than islets in other solutions. When exposed to glucose, the islets secreted insulin, demonstrating normal functionality. Moving beyond cell cultures, Ameer’s team tested the gel in small and large animal models. Liquid at room temperature, the material turns into a gel at body temperature, so it’s simple to apply and easily stays in place.
In the animal studies, the gel effectively secured the islets onto the omentum of the animals. Compared to the current methods, more islets survived, and, over time, the animals restored normal blood glucose levels. According to Ameer, the success is partially due to the new material’s biocompatibility and antioxidant nature.
“Islets are very sensitive to oxygen,” Ameer said. “They are affected by both too little oxygen and too much oxygen. The material’s innate antioxidant properties protect the cells. Plasma from your own blood doesn’t offer the same level of protection.”
Integrating into tissues
After about three months, the body resorbed 80-90% of the biocompatible gel. But, at that point, it was no longer needed.
“What was fascinating is that the islets regenerated blood vessels,” Ameer said. “The body generated a network of new blood vessels to reconnect the islets with the body. That is a major breakthrough because the blood vessels keep the islets alive and healthy. Meanwhile, our gel is simply resorbed into the surrounding tissue, leaving little evidence behind.”
Next, Ameer aims to test his hydrogel in animal models over a longer period of time. He said the new hydrogel also could be used for various cell replacement therapies, including stem cell-derived beta cells for treating diabetes.
