Category: Metabolic Disorders

New Weight Loss Drug Targets Four Hormone Receptors

Photo by I Yunmai on Unsplash

In the US, drugs like semaglutide are used by over 15 million adults in the U.S., or 4.5% of the population for diabetes and also weight loss. Despite their effectiveness, they have drawbacks. Their effect may not last after discontinuing use, and side effects including osteoporosis and muscle loss have raised concerns about long-term harms. They also induce nausea, which can make it difficult to stay the course of treatment.

Now Tufts researchers led by Professor Krishna Kumar, have designed a new, next-generation compound with hopes that it could be more effective with fewer side effects, which they report in a paper in the Journal of the American Chemical Society

While weight loss drugs currently on the market and in development target one, two, or even three hormone receptors related to glucose metabolism and the desire to eat, the Tufts team has identified a fourth target that could potentially further enhance the control strategy.

“Obesity is linked to over 180 different disease conditions, including cancer, cardiovascular disease, osteoarthritis, liver disease, and type 2 diabetes, and affects over 650 million people worldwide,” said Kumar. “What drives us is the idea that we can design a single drug to treat obesity and simultaneously mitigate the risk of developing a long list of health problems plaguing society.”

How the Drugs Work

After a meal, the hormone glucagon-like peptide 1 (GLP-1) is released to help stimulate the production of insulin and the uptake of glucose in muscle and other tissues. With the cells now loaded with fuel, the level of glucose in the blood returns to normal. Semaglutide uses GLP-1 with slight modifications to increase its availability in the bloodstream. Its success in controlling blood glucose has prompted the American Diabetes Association to recommend it and other GLP-1-based drugs as the new first line injectable treatments for diabetes, ahead of insulin.

But GLP-1 also acts directly on the brain, prompting satiety after a meal, and it slows down the rate at which stomach contents are emptied into the intestines, evening out the release of nutrients and glucose into the bloodstream. That’s why it has also become extremely popular as a weight loss treatment.

It’s still not a perfect drug strategy for weight loss, though. “The biggest problem with GLP-1 drugs is that they have to be injected once a week, and they can induce a very strong feeling of nausea,” said Kumar. “As much as 40% of people using these drugs give up after the first month.”

A second hormone released after eating is glucose-dependent insulinotropic peptide (GIP). It also makes us feel full after a meal. GIP looks a lot like GLP-1, so rather than administer two drugs, researchers created one peptide that incorporates structural elements of both – what’s called in drug development a chimera. That drug, tirzepatide, has the added benefit of significantly reducing nausea. As a more tolerable treatment, it may overtake semaglutide in the weight loss market. 

“And then there is a third hormone, glucagon,” said Kumar. “Paradoxically, it actually increases blood glucose, but at the same time increases the expenditure of energy in cells of the body, raises body temperature, and suppresses appetite.” By adding glucagon to the mix, GLP-1 and GIP end up neutralizing its glucose-enhancing effect, leaving the remaining functionalities of all three hormones working together to enhance weight loss.

Glucagon is also similar in structure to GLP-1 and GIP, so drug developers created a single chimera peptide that incorporates elements of all three hormones, which can be recognised by their three separate receptors. That drug, called retatrudide, is currently in clinical trials that indicate even greater achievable weight loss (up to 24%) compared to the original GLP-1 drugs (6-15%).

Going for the Weight Loss Gold Standard with a Fourth Target

“The goal that people are trying to shoot for is bariatric surgery,” said Kumar. That’s a surgical procedure significantly reducing the size of the stomach, which can achieve long-lasting weight loss up to 30%. “For individuals with persistent obesity and potential deadly associated conditions, it becomes a necessary but invasive treatment.” 

Current injectable weight loss drugs still fall short of that gold standard, so the Tufts chemists are focused on a drug redesign that could match the 30% weight loss outcome. 

“There is one more hormone we wanted to bring in to complete a weight control quartet,” said Tristan Dinsmore, a graduate student in the Kumar lab and the lead author of the study. “It’s called peptide YY (PYY). This molecule is also secreted by the gut after we eat a meal, and its job is to reduce appetite and slow the process of emptying food from the stomach, but via different mechanisms than either GLP-1 or GIP. It may also be involved in directly ‘burning off’ fat.”

PYY is from a separate and structurally unrelated class of hormones than the first three, so blending its structure into a chimeric peptide that also mimics GLP-1, GIP, and glucagon was not easy. Instead, the Tufts team was able to join two peptide segments end-to-end, creating a new ‘tetra-functional’ clinical candidate.

“One of the limitations of the current drugs is that individual variation, possibly including how people express target receptors or respond to their corresponding hormones, can lead to lesser than desired weight loss outcomes in many patients,” said Martin Beinborn, visiting scholar in the Department of Chemistry. “By hitting four different hormone receptors at the same time, we hope to improve the chances of averaging out such variation toward the goal of achieving greater and more consistent overall effectiveness.”

“A second issue is that patients tend to regain weight after discontinuing currently available GLP-1 related drugs,” said Beinborn, who notes that lifestyle changes should ideally be a complement to medication treatment. This two-pronged approach will not only support reaching and keeping one’s target weight, but may also help preserve bone and muscle mass.

“Recent studies indicate that weight rebound after drug discontinuation is delayed with the newer, more effective GLP-1 mimetics,” he said. “Extending from this observation, one may speculate that multi-chimeras along the lines of the one we discovered could get us closer to the bariatric surgery standard of lasting weight loss.”

Source: Tufts University

Rates of Obesity Are Soaring Worldwide: Have We Been Misunderstanding the Problem?

Photo by Andres Ayrton on Pexels

By Jesse Copelyn

Authors of a recent Lancet report argue that obesity should not just be seen as a risk factor for other diseases – but in some cases, should be seen as a disease itself. The position could change how we treat obesity globally. In the first of this two-part Spotlight series, we break down the debate around the issue, and its implications for health policy.    

In 1990, just 2% of all young people around the world aged 5 to 24 were living with obesity. By 2021, this figure had more than tripled to over 6%. This is according to a recent study, which relied on Body Mass Index (BMI) data from 180 countries and territories around the world. It estimates that the rise in obesity among children and young people will only continue in the coming decades.

South Africa certainly isn’t immune to the crisis. A survey conducted in 2021/2022 found that 16% of all children aged 6 to 18 were “severely overweight”. Meanwhile, World Health Organization (WHO) data suggests that about 30% of all adults in South Africa are living with obesity, meaning a BMI of over 30, which is almost double the global level.

BMI, which simply looks at a person’s weight in relation to their height, is a crude measure of obesity. For instance, a person may have a high BMI simply because they have a lot of muscle rather than fat. But while it is agreed that BMI is a flawed indicator at the individual level, many experts recommend using it as a rough proxy for “health risk at a population level”.

For instance, a study which collected data on nearly three million people found that those who had very high BMI levels were, on average, more likely to die at an early age. The study also found that this was true of people with very low BMI levels (those who were underweight). In this context, the above figures paint a concerning picture.

Given the rising rates, experts argue that we need health systems to be able to track and respond to obesity urgently. But, according to a Lancet Commission published in January, health systems around the world may struggle to do this, because of a failure to accurately conceptualise and measure what obesity actually is.

The Lancet commission was developed by 58 experts from different medical specialties and though it has been the subject of debate, it has since been widely endorsed as a new way to understand obesity. Spotlight takes a look at what it concluded.

Delaying treatment for no reason

Obesity is often regarded as a risk factor for other diseases, for instance, type 2 diabetes. But according to the commission, there are certain cases in which obesity is not just a risk factor, but a disease itself – one that should be immediately treated.

One of the reasons for this is that obesity not only contributes to the emergence of other conditions but sometimes leads to clinical symptoms directly. For example, the cartilage that protects the joints in a person’s knees can sometimes become eroded when adults carry too much weight. In this case, a person could suffer from joint pain, stiffness and reduced mobility where obesity is clearly the cause.

Take another example. If fat deposits build up in the abdomen, this may limit how much the lungs can expand, causing breathlessness. Similarly, a build-up of fat around the neck can narrow a person’s upper airways, which can cause sleep apnoea.

Thus, obesity is not simply something which increases the risk of developing a separate disease in the future – but something which can directly (and presently) affect the functioning of organs.

More broadly, the commission argues that by hindering a person’s “mobility, balance and range of motion” obesity can in certain cases “restrict routine activities of daily living”. In these instances, obesity is a disease by definition, according to the commission. This is given that it defines disease as a “harmful deviation from the normal structural or functional state of an organism, associated with specific signs and symptoms and limitations of daily activities”.

But why does this conceptual debate matter?

Because at present, people often have to wait for other diseases to crop up before insurers or public health systems cover them for weight loss drugs or bariatric surgery – a procedure to help with weight loss and improve obesity-related health conditions. And when they do cover these services, it is often only after severe delay. Because obesity is only considered to be a risk factor, it isn’t typically treated with the same urgency as life-threatening diseases, according to the authors of the commission.

Professor Frances Rubino, the lead author of the commission, details how this problem manifests in the healthcare system.

“I’ve been doing bariatric surgery for 25 years in four different countries; in America, Italy, France and the UK,” he tells Spotlight, “In all of those countries, to meet the criteria for surgery people very often have to undergo six to 12 months of weight monitoring before their surgery is covered. So systematically you delay treatment”.

He continues: “Someone who has clinical obesity and has heart failure as a result of it is waiting for a year for what reason? That condition will only worsen and if the patient is still alive, the treatment [is] going to cost the same amount to the payer but it’s going to be less effective.”

Can’t people just diet?

One of the reasons that some academics have historically been reluctant to classify obesity as a disease is because of a fear that this may reduce people’s agency – instead of taking proactive steps to diet and exercise, people with obesity may simply view themselves as afflicted by a disease.

The belief that people with obesity can simply diet their way out of their situation is in fact partially why Rubino’s patients were forced to wait long periods of time before receiving bariatric surgery.

Rubino explains: “In America, many private payers [i.e. medical insurance schemes] have required weight monitoring programmes, where patients do nothing else other than see a dietician for 12 months, and if they skip one appointment, they have to start all over again. I think that in some cases, this has been misguided by the idea that you want to see if obesity can be reversed by somebody going on a diet.”

This, according to him, is a “misconception”, arguing that if someone faces such severe levels of obesity that they require surgery, diet is unlikely to offer a solution.

Indeed, research has shown that it’s very rare for people with obesity to lose large amounts of weight quickly without surgery or medication. For instance, a study on over 176 000 patients in the UK found that among men with “simply obesity” or a BMI of 30-34.9, only 1 in 210 were able to achieve a “normal” weight level within a year. Among men with morbid obesity or BMI of 35 or more, the chance was less than 1 than in 1000. Chances for women were roughly twice as good as men’s – so still exceedingly small.

Thus, if someone is severely obese and their excess weight is causing life-threatening symptoms, putting them on a diet for a year is unlikely to result in the urgent changes that may be required for them to get better. In fact, Rubino argues that they may simply die of their condition in the interim.

Taking a medical approach more quickly is easier now than ever before due to the regulatory approval of GLP-1 agonists like semaglutide and tirzepatide – Spotlight previously reported on the availability of these new diabetes and weight loss medicines in South Africa. An article by WHO officials from December states that because of the approval of these medicines “[h]ealth systems across the globe now may be able to offer a treatment response integrated with lifestyle changes that opens the possibility of an end to the obesity pandemic”.

Not all people with obesity are ill

There is a more scientific argument against categorising obesity as a disease. This is that while obesity can sometimes result in the negative health symptoms discussed above (like respiratory issues or reduced mobility) it doesn’t always do this.

In fact, the commission acknowledges that some people with obesity “appear to be able to live a relatively healthy life for many years, or even a lifetime”. One of the reasons for this is that excess fat may be stored in areas that don’t surround vital organs. For instance, if fat is stored in the limbs, hips, or buttocks, then this may cause less harm than if it is stored in the stomach.

Since obesity doesn’t always cause health problems, it isn’t always a disease. In order to deal with this conceptual hurdle, the commission classifies obesity into two categories – clinical and preclinical obesity.

If a person has pre-clinical obesity, this means they have a lot of excess fat, but no obvious health problems that have emerged as a result. In this case, obesity is not classified as a disease, though it may still increase the chance of future health problems (depending on a range of factors, like family history).

For a person to have clinical obesity, they must have a lot of excess fat as well as health problems that have already been directly caused by this. It is this that the commission defines as a disease.

This classification system, according to Rubino, ensures not only that we urgently treat people living with clinical obesity, but also that we don’t overtreat people – since if a person falls into the pre-clinically obese group, then they may not need treatment.

But if we’re going to treat clinical obesity as a disease, we’ll need clear methods of diagnosing people. Since BMI is deeply flawed and provides little information about whether a person is ill at the individual level, health systems will need something else. In part 2 of this Spotlight special series, we’ll discuss the options offered by the commission, and how this all relates to the situation in South Africa.

Republished from Spotlight under a Creative Commons licence.

Read the original article.

Midlife Weight Loss Linked to Longer, Healthier Lives

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Losing weight via lifestyle adjustments can deliver significant long-term health benefits, without the need for surgery or anti-obesity drugs. Alongside preventing diabetes, it can help ward off chronic conditions including arterial and pulmonary diseases as well as cancers.

A University of Helsinki study tracked 23 000 individuals from Finland and the UK, aged 30 to 50 at the outset, over a period of 12 to 35 years. Health benefits were found in overweight men and women who lost an average of 6.5% of their body weight in early middle age and maintained it throughout the 12–35-year follow-up period. Weight maintenance is crucial. 

“The benefits of lifestyle-based weight management are widely discussed even though studies have found it surprisingly difficult to demonstrate health benefits beyond the prevention of diabetes,” notes Professor Timo Strandberg.  

The study he led is now filling this gap. 

“I hope the findings will inspire people to see that lifestyle changes can lead to major health improvements and a longer life. This is particularly important today as more people are overweight than when the collection of our research data began 35 years ago.” 

The study also supports the view that, for optimal health, a lifelong body mass index (BMI) under 25 is ideal.   

The study was published in JAMA Network Open, the open-access journal of the American Medical Association.

Source: University of Helsinki

Timely Initiation of Statins in Diabetes Shown to Dramatically Reduce Cardiovascular Risk

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Despite clinicians recommending that many patients with diabetes take statins, nearly one in five opt to delay treatment. In a new study, researchers from Mass General Brigham found that patients who started statin therapy right away reduced the rate of heart attack and stroke by one third compared to those who chose to delay taking the medication. The results, which can help guide decision-making conversations between clinicians and their patients, are published in the Journal of the American Heart Association.

“I see patients with diabetes on a regular basis, and I recommend statin therapy to everyone who is eligible,” said senior author Alexander Turchin, MD, MS, of the Division of Endocrinology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “Some people refuse because they want to first try lifestyle interventions or other drugs. But other interventions are not as effective at lowering cholesterol as starting statin therapy as soon as possible. Time is of the essence for your heart and brain health.”

Heart attacks and strokes remain the leading cause of complications and mortality for patients with diabetes. Statin therapy reduces risk of these cardiovascular events by preventing plaque buildup in the blood vessels.

The researchers used an artificial intelligence method called Natural Language Processing to gather data from the electronic health records of 7239 patients at Mass General Brigham who ultimately started statin therapy during the nearly 20-year study period. The median patient age was 55, with 51% being women, 57% white, and a median HbA1c of 6.9.

Nearly one-fifth (17.7%) of the patients in the study declined statin therapy when it was first recommended by their clinicians, then later accepted the therapy (after a median of 1.5 years) upon repeated recommendation by their clinician. Of those who delayed, 8.5% had a heart attack or stroke. But for patients who started statins immediately, the rate of those cardiovascular events was just 6.4%.

“Clinicians should recognize the increased cardiovascular risk associated with delaying statin therapy for patients with diabetes and use this information to guide shared decision-making conversations with their patients,” said Turchin.

Source: Mass General Brigham

Abdominal Fat More Linked to Psoriasis Risk than Total Body Fat

Findings in the Journal of Investigative Dermatology reinforce the role of weight management in psoriasis care

Source: Pixabay CC0

Researchers have found that central body fat, especially around the abdomen, is more strongly linked to psoriasis risk than total body fat, particularly in women. This link between central fat and psoriasis remained consistent regardless of genetic predisposition, indicating that abdominal fat is an independent risk factor. The study in the Journal of Investigative Dermatology, published by Elsevier, provides insights that could help improve early risk prediction and guide personalised prevention strategies.

While it is well established that increasing levels of body fat raise the risk of developing psoriasis, the impact of specific fat distribution and genetics remains unclear.

Researchers of the current study analysed data from over 330 000 participants with White British ancestry in the UK Biobank, including more than 9000 people with psoriasis. They examined 25 different measures of body fat using both traditional methods and advanced imaging techniques, assessing how each was associated with psoriasis.

Lead investigator Ravi Ramessur, MD, St John’s Institute of Dermatology, King’s College London, explains, “Our research shows that where fat is stored in the body matters when it comes to psoriasis risk. Central fat – especially around the waist – seems to play a key role. This has important implications for how we identify individuals who may be more likely to develop psoriasis or experience more severe disease, and how we approach prevention and treatment strategies.”

Senior author Catherine H. Smith, MD, also at King’s College London, adds, “As rates of obesity continue to rise globally, understanding how different patterns of body fat influence chronic inflammatory conditions such as psoriasis is important. Our findings suggest that central body fat contributes to psoriasis risk irrespective of genetic predisposition and reinforces the importance of measuring waist circumference and pro-active healthy weight strategies in psoriasis care.”

Because this study only included individuals of White British ancestry from the UK Biobank, the generalisability of these findings to more diverse populations may be limited. Future studies incorporating datasets with dermatologist-confirmed diagnoses and broader ethnic representation will be important to further validate these associations and refine risk stratification approaches.

Dr Ramessur notes, “We were surprised by how consistently strong the association was across different central fat measures and how much stronger the effect was in women. The observed links between central body fat and psoriasis suggest that there may be underlying biological mechanisms contributing to the disease that are not yet fully understood and which warrant further investigation.”

In an accompanying editorial Joel M. Gelfand, MD, MSCE, FAAD, at the University of Pennsylvania Perelman School of Medicine, points to the potential of incretin therapy for psoriatic disease. Incretins are gut-derived hormones, principally glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), that regulate glucose, digestion, and appetite, and are approved for treatment of diabetes, obesity, and obesity-associated obstructive sleep apnoea.

Dr Gelfand comments, “The strong relationship between psoriasis and obesity and the emerging promise of glucagon-like peptide-1 receptor agonists (GLP1RA) for reducing psoriasis morbidity is a call to action for large scale clinical trials of GLP1RA monotherapy for treatment of psoriasis. Our current paradigm of just focusing on the skin and joint manifestations when treating psoriasis is outdated in the context of our evolving understanding of the tight relationship of psoriasis, obesity, and cardiometabolic disease.“

Source: Elsevier

Adult-onset Type 1 Diabetes Increases Cardiovascular Risk, Especially in 40s and Older

Source: Pixabay CC0

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.

Source: Karolinska Institutet

Could the Brain be Targeted to Treat Type 2 Diabetes?

Source: CC0

Successfully treating type 2 diabetes may involve focusing on brain neurons, rather than simply concentrating on obesity or insulin resistance, according to a study published in the Journal of Clinical Investigation.  

For several years, researchers have known that hyperactivity of a subset of neurons located in the hypothalamus, called AgRP neurons, is common in mice with diabetes. 

“These neurons are playing an outsized role in hyperglycaemia and type 2 diabetes,” said UW Medicine endocrinologist Dr Michael Schwartz, corresponding author of the paper.

To determine if these neurons contribute to elevated blood sugar in diabetic mice, researchers employed a widely used viral genetics approach to make AgRP neurons express tetanus toxin, which prevents the neurons from communicating with other neurons. 

Unexpectedly, this intervention normalised high blood sugar for months, despite having no effect on body weight or food consumption.   

Conventional wisdom is that diabetes, particularly type 2 diabetes, stems from a combination of genetic predisposition and lifestyle factors, including obesity, lack of physical activity and poor diet. This mix of factors leads to insulin resistance or insufficient insulin production.  

Until now, scientists have traditionally thought the brain doesn’t play a role in type 2 diabetes, according to Schwartz. 

The paper challenges this and is a “departure from the conventional wisdom of what causes diabetes,” he said. 

The new findings align with studies published by the same scientists showing that injection of a peptide called FGF1 directly into the brain also causes diabetes remission in mice. This effect was subsequently shown to involve sustained inhibition of AgRP neurons.

Together, the data suggest that, while these neurons are important for controlling blood sugar in diabetes, they don’t play a major role in causing obesity in these mice, the researchers noted in their report.  

In other words, targeting these neurons may not reverse obesity, even as it causes diabetes to go into remission, Schwartz explained. 

More research is needed on how to regulate activity in these neurons, and how they become hyperactive in the first place, he said. Once these questions are answered, Schwartz said that a therapeutic approach might then be developed to calm them down. 

This approach could represent a shift in how clinicians understand and treat this chronic disease, Schwartz said.  He noted, for instance, that semaglutide and other new drugs used to treat type 2 diabetes are also able to inhibit AgRP neurons.  

The extent to which this effect contributes to the antidiabetic action of these drugs is unknown. Further research might help scientists to better understand the role of AgRP neurons in how the body normally controls blood sugar, and to ultimately translate these findings into human clinical trials, he added.  

Source: University of Washington School of Medicine/UW Medicine

Metabolic Syndrome Linked to Increased Risk of Young-onset Dementia

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Having a larger waistline, high blood pressure and other risk factors that make up metabolic syndrome is associated with an increased risk of young-onset dementia, according to a study published on April 23, 2025, online in Neurology®, the medical journal of the American Academy of Neurology. Young-onset dementia is diagnosed before the age of 65. The study does not prove that metabolic syndrome causes young-onset dementia, it only shows an association.

Metabolic syndrome is defined as having excess belly fat plus two or more of the following risk factors: high blood pressure, high blood sugar, higher than normal triglycerides, which are a type of fat found in the blood, and low high-density lipoprotein (HDL) cholesterol, or “good” cholesterol.

“While most dementia is diagnosed in older age, young-onset dementia occurs while a person is still working and perhaps raising a family,” said study author Minwoo Lee, MD, PhD, of Hallym University Sacred Heart Hospital in Anyang, South Korea. “Our study found having metabolic syndrome in middle age is a risk factor for young-onset dementia.”

For the study, researchers reviewed national health insurance data in South Korea to identify nearly two million people between the ages of 40 and 60 who had a health check-up. The check-up included measurements of waist circumference, blood pressure, blood sugar, triglyceride and cholesterol levels. Of all participants, 25% had metabolic syndrome.

Over an average follow-up period of eight years, 8921 people, or 0.45% of all participants, developed dementia. For those with metabolic syndrome, the incidence rate was 0.86 cases per 1000 person-years, compared to 0.49 cases for those without metabolic syndrome. Person-years represent both the number of people in the study and the amount of time each person spends in the study.

After adjusting for age, education and health factors such as level of physical activity, depression and stroke, researchers found metabolic syndrome was associated with a 24% higher risk of dementia. When looking at specific types of dementia, it was associated with a 12% increased risk of Alzheimer’s disease and a 21% increased risk of vascular dementia.

Researchers found female participants with metabolic syndrome had a 34% increased risk of dementia compared to male participants who had a 15% increased risk. People in their 40s had a greater risk than people in their 50s.

Researchers found each component of metabolic syndrome was associated with an increased risk of dementia, which was cumulative. People with all five components had a 70% increased risk of dementia.

“Our findings suggest that lifestyle changes to reduce the risk of metabolic syndrome, such as eating a healthy diet, exercising regularly, maintaining a healthy weight, quitting smoking and reducing stress, may help reduce the risk of young-onset dementia,” said Lee. “Future research that follows people over longer periods of time and uses brain scans to look for biomarkers of dementia is needed to confirm and expand upon our findings.”

A limitation of the study was that researchers did not review genetic risk factors for Alzheimer’s disease.

The study was supported by the Korean National Research Foundation.

Source: American Academy of Neurology

Dual-action Approach Targeting Inflammation Shows Potential as Type 1 Diabetes Treatment

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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.”

Source: Indiana University

Popular Diabetes Drugs may Protect Against Alzheimer’s Disease

Neurons in the brain of an Alzheimer’s patient, with plaques caused by tau proteins. Credit: NIH

A study led by researchers in the University of Florida College of Pharmacy has found that a pair of popular glucose-lowering medications may have protective effects against the development of Alzheimer’s disease and related dementias in patients with Type 2 diabetes.

In research published in JAMA Neurology on April 7, UF researchers studied Medicare claims data of older adults with Type 2 diabetes to assess the association among glucagon-like peptide-1 receptor agonists, or GLP-1RAs, sodium-glucose cotransporter-2 inhibitors, or SGLT2is, and the risk of Alzheimer’s disease and related dementias.

The research is supported by funding from the National Institute on Aging and the National Institute of Diabetes and Digestive and Kidney Diseases, both part of the National Institutes of Health.

The data showed a statistically significant association between a lower risk of Alzheimer’s and the use of GLP-1RAs and SGLT2is compared with other glucose-lowering medications. According to the researchers, the findings indicated that the two drugs may have neuroprotective effects for people without diabetes and may help slow the rate of cognitive decline in Alzheimer’s patients.

Serena Jingchuan Guo, MD, PhD, an assistant professor of pharmaceutical outcomes and policy and the study’s senior author, said these findings may point to new therapeutic uses for drugs commonly used to treat Type 2 diabetes and obesity.

“It’s exciting that these diabetes medications may offer additional benefits, such as protecting brain health,” Guo said. “Based on our research, there is promising potential for GLP-1RAs and SGLT2is to be considered for Alzheimer’s disease prevention in the future. As use of these drugs continues to expand, it becomes increasingly important to understand their real-world benefits and risks across populations.”

As the study only included patients with Type 2 diabetes, Guo said next steps include evaluating the effects of the two drugs in broader populations by using recent, real-world data that captures their growing use in clinical settings.

“Future research should focus on identifying heterogeneous treatment effects – specifically, determining which patients are most likely to benefit and who may be at greater risk for safety concerns,” Guo said.

Source: University of Florida