Category: Metabolic Disorders

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Major Trial Examines Artificial Sweeteners in Soft Drinks

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Researchers at the University of Liverpool have conducted the longest and most comprehensive randomised controlled trial on non-nutritive sweetened (NNS) soft drinks.

Non-nutritive sweeteners are low- or no-calorie alternatives to sugar used to sweeten foods and drinks. The 104-week clinical trial shows NNS beverages ie, diet beverages are equivalent to water for long term weight management.

Professor Jo Harrold, Dean of Psychology at the University of Liverpool alongside Professor Jason Halford, Professor, Biological Psychology & Health Behaviours at the University of Leeds (formerly of the University of Liverpool) conducted the peer-reviewed research funded by the American Beverage Association. The research team was independent of the funder and had full control over the analysis and reporting of their findings.

The major new study was published in the British Journal of Nutrition and provides long-term clinical evidence that NNS beverages – specifically those containing aspartame, acesulfame potassium (acesulfame‑K), and sucralose – are equivalent to water in supporting weight loss and long‑term weight maintenance.

The SWITCH trial followed 493 adults with overweight or obesity through a structured behavioural weight management programme. Participants were randomised to consume either water or commercially available diet beverages, daily, with sweeteners provided at levels well within established European Food Safety Authority (EFSA) safety thresholds.

Overall, the results do not support concerns that NNS beverages disrupt appetite regulation or have long term metabolic harm.

Key outcomes include:

  • Equivalent weight loss between NNS beverages and water at 104 weeks (−4.8 kg vs −3.7 kg; nonsignificant difference).
  • Sustained weight reduction over two years in both groups, even during the final unassisted year.
  • Decrease in waist and hip circumference and improvement in body composition, and several metabolic biomarkers in both groups.
  • No clinically meaningful difference in effects such as blood pressure and cholesterol, associated with long-term consumption of either aspartame, acesulfame‑K, or sucralose or water.
  • Sugar intake decreased in both groups, with slightly greater reductions in the NNS group.

Importantly, the findings directly address recent World Health Organization (WHO) guidance, which advised against using non-sugar sweeteners for weight control due to uncertainty in observational studies. The SWITCH trial provides long-duration, randomised controlled evidence which can be used to inform global guidelines.

Professor Joanne Harrold, said: “The University of Liverpool is one of the UK’s leading research-intensive higher education institutions, with a key focus on public health. These latest findings show that concerns about sweeteners disrupting appetite or causing weight gain are not supported when tested in a rigorous, long-term randomised trial. We hope this evidence informs future WHO guidance and public health policy.

The effectS of non-nutritive sWeetened beverages on appetITe during aCtive weigHt loss (SWITCH) trial was conceived and designed by researchers in the context of the need to reduce sugar in the diet and to address questions about the potential effects on appetite regulation of using sweeteners as a substitute. This latest published work continues from previously published evidence in the International Journal of Obesity in 2023.

Professor Jason Halford, University of Leeds and University of Liverpool, concluded: “This study provides the long‑term clinical evidence that has been missing from international discussions. For people trying to manage their weight, non‑nutritive sweetened beverages offer an effective alternative to sugar‑sweetened drinks – and perform equivalently to water over two years.”

Source: University of Liverpool

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Personalised Testing in Diabetes Shows Benefits in Protecting Kidney Function

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Chronic kidney disease (CKD). Credit: Scientific Animations CC4.0

Type 2 diabetes increases the risk of chronic kidney disease, making prevention of kidney failure a key part of treatment. Newer diabetes medications, including GLP-1s and SGLT2 inhibitors, can reduce the risk of kidney disease, but previous studies have included large proportions of patients who already had signs of kidney damage, making it unclear whether the findings applied to patients without kidney damage.

A new study led by Mass General Brigham researchers found that GLP-1 agonists and SGLT2 inhibitors reduced the risk of kidney deterioration in patients with diabetes who had protein in their urine, a sign of kidney damage, before treatment. However, the researchers found little evidence of kidney benefit among patients without protein in their urine. They also showed that sulfonylureas, an older class of diabetes medication, led to faster declines in kidney function in patients with diabetes who didn’t have protein in their urine. Results are published in the BMJ.

“Our study shows that we need to tailor diabetes treatment to the individual patient instead of using a one-size-fits-all approach,” said corresponding author Alexander Turchin, MD, MS, of the Division of Endocrinology in the Mass General Brigham Department of Medicine. “A simple urine test could help doctors assess whether a patient may receive kidney protection from GLP-1 receptor agonists or SGLT2 inhibitors and whether sulfonylureas could pose additional risk.”

Tracking kidney outcomes

The researchers analysed medical record data from 75 455 patients with type 2 diabetes across the U.S., including 13,872 who presented with protein in their urine. They followed the patients for up to five years and compared the risk of developing chronic kidney disease among patients prescribed GLP-1s and SGLT2 inhibitors with those prescribed sulfonylureas or DPP4i. All patients had moderate cardiovascular risk and were receiving metformin as their primary diabetes medication.

Among patients with protein in their urine, GLP-1s and SGLT2 inhibitors were associated with substantially better kidney outcomes than DPP4i. However, GLP-1s and SGLT2 inhibitors did not appear to provide a significant kidney benefit in patients without protein in their urine. Among patients without protein in their urine at baseline, treatment with sulfonylureas was associated with an increased risk of kidney deterioration compared with DPP4i.

Gap for lower-risk patients

Further research is needed to identify therapies to prevent kidney disease in the large population of patients with type 2 diabetes who don’t present with protein in their urine, the researchers say.

“These findings will allow us to individualise medication choices that maximally benefit the patient in front of us rather than for the hypothetical ‘average person,'” said Turchin. “Patients and their doctors should discuss how to balance these different risks and benefits in their individual circumstances when choosing their type 2 diabetes medications.”

Source: Mass General Brigham

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Stress May be Fuelling SA’s Metabolic Disease Risk

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Chronic stress may be doing far more than affecting South Africans’ mental health – it could be contributing to the country’s growing burden of obesity, diabetes and other metabolic disorders, many of which are also major risk factors for cardiovascular disease (CVD).

While stress is often viewed as an unavoidable part of modern life, mounting scientific evidence suggests that prolonged psychological stress can trigger biological changes that increase the likelihood of developing obesity, type 2 diabetes (T2D) and CVD.

Prof Naidoo, CEO of the Heart and Stroke Foundation SA reminds us that day-to-day stressors has a cumulative effect affecting not just ones’ immune system, but also impacts eating, exercise and other vegetative signs, such as poor sleeping patterns. Ultimately, she says, the cardiovascular system has reduced capacity in the face of cumulative stressors.

This makes the stress-metabolism connection particularly relevant during Heart Awareness Month this September, when attention turns to the factors that can influence long-term heart-health.

The warning comes at a time when many South Africans are battling significant workplace and financial pressures. According to Gallup’s recent 2026 State of the Global Workplace report1, 36% of South African employees reported experiencing stress, while the 2025 Profmed Stress Index found that financial uncertainty and workplace pressure remain among the leading causes of stress among South African professionals.

The two-way relationship between stress and metabolic health (1)

“Most people understand that stress can affect their mood and sleep, but few realise that chronic stress can also disrupt the body’s metabolism,” says Nicole Jennings, spokesperson for Pharma Dynamics.

“When stress becomes chronic, the body remains in a prolonged state of alertness and continues producing elevated levels of cortisol, often referred to as the stress hormone. Over time, this can contribute to increased blood glucose levels, insulin resistance and the accumulation of harmful visceral fat around the abdominal organs in certain individuals.”

Research shows that prolonged activation of the body’s stress-response system may disrupt glucose metabolism, reduce insulin sensitivity and encourage fat storage, all of which are strongly associated with metabolic disease.

“But the relationship goes both ways. Long-term emotional or work-related stress can increase the likelihood of developing these conditions, while metabolic disorders can, in turn, alter the body’s stress-response systems, potentially increasing vulnerability to the effects of stress.

“Because metabolic disorders can disrupt the immune system and affect the brain’s chemical balance, they may intensify how the body reacts to pressure. The result is a vicious cycle where chronic stress contributes to metabolic dysfunction, and metabolic dysfunction may further impair the body’s ability to cope with stress. Prof Naidoo states that chronic stress has a negative effect on our health outcomes in ways that are not often obvious. An example of this is excessive eating during stressful episodes resulting in weight gain which is a potential driver for type 2 diabetes. Overweight and obesity is also, in turn, a driver for raised blood pressure and hypertension.

A growing metabolic health crisis

The concern is particularly relevant for South Africa, where metabolic disorders are becoming increasingly common.

According to the International Diabetes Federation (IDF), approximately 2.3 million South African adults are currently living with diabetes, representing a prevalence rate of 7.2% among adults. The country has the fourth-highest number of adults living with diabetes in Africa.

Obesity, another major risk factor for metabolic disease, remains a significant public health challenge. Approximately one in two South African adults is living with excess weight or obesity, placing millions at increased risk of diabetes, heart disease and other metabolic conditions (2).

“Many people focus on diet and exercise when discussing metabolic health, and rightly so,” says Jennings. “However, stress management is often the missing piece of the puzzle. You can be eating relatively well, but if you’re living in a constant state of stress, your body may still be experiencing metabolic consequences.” There is increasing evidence of the gut-brain connection where research is producing results that show that the type of diet you consume also plays a role in mental health and well-being says Prof Naidoo.

Why workplaces should pay attention

This highlights the important role employers can play in supporting both mental and physical health.

Studies have found that workplace stress is associated with a higher risk of developing metabolic syndrome, a cluster of conditions that includes elevated blood pressure, high blood sugar, excess abdominal fat and abnormal cholesterol levels. Together, these factors can significantly increase the risk of heart disease and stroke.

In South Africa, where economic uncertainty, job insecurity, rising living costs and demanding workloads contribute to stress levels, workplace wellness programmes could provide an important opportunity for prevention.

Small changes can make a big difference

Fortunately, Jennings says the stress-metabolism connection is not inevitable. Regular physical activity, sufficient sleep, a balanced diet, avoiding smoking, moderating alcohol intake and incorporating mindfulness practices – along with strong social support networks – have all been shown to help regulate the body’s stress response and support better metabolic health.

She encourages South Africans to view stress management not only as an essential component of mental health, but as part of a broader approach to protecting metabolic and heart health too.

“Managing stress isn’t a luxury – it’s an important part of preventing chronic disease. By recognising the impact stress has on the body and taking proactive steps to address it, individuals can improve both their mental well-being and long-term metabolic health.”

Prof Naidoo encourages those facing unmanageable stress to seek access to healthcare as there are specialist health care practitioners that are trained for stress management and mental health conditions.

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Women with Type 2 Diabetes More Likely to Develop Mental Health Conditions

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Men, on the other hand, experience more cardiovascular and renal disease post-diagnosis

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In the years following type 2 diabetes diagnosis, women are more likely to develop mental health conditions, while men are more likely to develop cardiovascular and renal complications, according to a study published August 25th in the open access journal PLOS Medicine by Fabiola Eto from Queen Mary University of London, UK, and colleagues.

Type 2 diabetes, a metabolic disorder defined by high blood sugar, results from resistance to or insufficient production of insulin. Globally, type 2 diabetes affects about 536.6 million people between 20 and 79 years old, or 10.5% of the population; by 2045, this number is expected to rise to 700 million. Cardiovascular disease, end-stage renal disease, and mental health disorders like depression and anxiety are all associated with type 2 diabetes. Women and men are known to experience these conditions differently, but research has not yet described the disease trajectories according to sex and age in people with type 2 diabetes.

Eto and colleagues examined anonymized health records from 28,720 men and women in the UK who developed type 2 diabetes between 2010 and 2020. Men constituted 62% of the cohort with a median age of 54 at type 2 diabetes onset; women were on average older at diagnosis.

In the years following diagnosis, 39% of the participants experienced at least one significant health event. The events’ trajectory and timing differed by sex. For example: women were more likely to develop mental health conditions post-diagnosis (8.1% compared to 5.3%) and to experience trajectories culminating in death, while men showed higher proportions of cardiovascular disease (8.4% compared to 5.3%), end-stage renal disease, and hypertension (21.1% compared to 20.2%). The researchers noted that on average, women used more health services and long-term prescriptions than men, which may contribute to the increased diagnoses.

There were several similarities between the sexes as well. Both women and men who had a combination of type 2 diabetes and a mental health condition experienced premature mortality compared to other trajectories. Across all age groups and sexes, hypertension was the most frequent event following type 2 diabetes.

Current UK medical guidelines lack sex-specific prevention strategies and management for type 2 diabetes and comorbidities, especially mental health conditions. This study highlights the need for healthcare interventions differentiated by characteristics like sex and age.

The authors add, “One of the clearest signals in our data was the sex difference. Younger women with type 2 diabetes were showing mental health complications earlier and more often than we expected, which suggests routine psychological screening should be incorporated into standard diabetes care. For men, the pattern looked different: cardiovascular and kidney risks tended to emerge earlier, pointing to a need for earlier monitoring and stronger strategies to support men’s engagement with their treatment over time.”

Provided by PLOS

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GLP-1s do not Cause Major Psychiatric Harm, Review Shows

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There is no link between the widely used diabetes and obesity medications known as GLP-1 receptor agonists and increased suicidal thoughts, depression or other serious psychiatric harm based on an integrative review of current scientific evidence conducted by researchers at New Mexico State University and the University of Nevada, Las Vegas.

The review, published in the journal Diabetology, traced the earliest concerns raised over GLP-1 RA therapies and found that after subsequent investigations, the medications do not increase psychiatric risk.

“GLP-1 RAs have become a cornerstone treatment for Type 2 diabetes and obesity, now used by tens of millions of patients worldwide,” said Jagdish Khubchandani, a professor of public health at NMSU, who co-authored the study with Kavita Batra, executive director of medical research and scholarly activities at the UNLV Kirk Kirkorian School of Medicine.

Reports that GLP-1s might trigger suicidal ideation, depression or anxiety began appearing  soon after the medications gained mainstream popularity. Those reports then prompted formal safety reviews by the U.S. Food and Drug Administration and the European Medicines Agency, beginning in 2023.

The research team analyzed five years of mechanistic, pharmacovigilance, observational and regulatory evidence to trace how early reports were investigated and how the scientific and regulatory consensus shifted over time. Earlier this year, the FDA removed its suicidality warning from GLP-1 medications.

“When reports of depression and suicidal thoughts first surfaced with GLP-1 RA use, they came from patients and doctors voluntarily reporting what they saw, and such reports can raise a question, but can’t answer it,” Batra said. “Since then, studies following millions of patients, including a pooled analysis of 91 clinical trials, have found no increase in psychiatric risk. But an answer for millions isn’t an answer for everyone. The right response is to screen and check in with each patient, not to take an effective treatment off the table.”

The review found that early warning signals were largely tied to one drug from selected patient groups, while larger controlled studies often pointed in contradictory directions – something the research team attributes to study design rather than the drugs themselves.

Khubchandani said spontaneous adverse-event reports can be skewed by media attention, by the fact that people with obesity and diabetes already have higher baseline rates of depression and suicidality, and by more frequent medical visits among treated patients that create more opportunities for symptoms to be reported. Controlled studies that account for these factors do not show exceptionally high risks, he added.

Still, the review found that some groups using GL-P1s may need closer monitoring. Patients already taking antidepressants or benzodiazepines showed a substantially amplified reporting signal for suicidal ideation, suggesting that any residual risk may be concentrated among those with pre-existing psychiatric vulnerability rather than the general patient population.

“Depression is more common in people with Type 2 diabetes than in the general population, and it works in both directions: Depression makes diabetes harder to manage, and diabetes makes depression more likely,” Batra said. “So, the mood symptoms a patient reports on any diabetes medication may have been there long before the prescription. That’s exactly why asking about mental health should be a routine part of diabetes care, not a special step reserved for when a drug is under suspicion.”

Khubchandani said the pace of research on GL-P1 medications needs to catch up with their pace of usage, particularly among groups like adolescents, those with serious mental illnesses and other groups underrepresented in clinical trials to date.

 “Just like for several other medications, the decision to use GLP-1 RA should include individualized screening of patients for psychiatric history and suicidality before starting treatment, watching more closely for patients with a history of mood disorders or concurrent psychiatric medication use, and educating patients and caregivers to report mood changes promptly,” Khubchandani said.

To read the review, visit https://www.mdpi.com/2673-4540/7/8/144.

Source: New Mexico State University

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Keto Diet Delivers Added Liver Benefits Beyond Weight Loss

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WashU Medicine researchers led a clinical trial testing three diets with different proportions of carbohydrates, fats and proteins and found all of them improved metabolic health, but a very low-carb ketogenic diet had additional benefits for liver health and blood sugar control. Credit: Katie Gertler/WashU Medicine

There is no shortage of popular diets to try, and they can generally produce weight loss if followed to the letter. But are all diet plans created equal in terms of reducing the cardiometabolic risks that come with obesity, such as Type 2 diabetes and liver disease?

A randomised clinical trial from Washington University School of Medicine in St. Louis suggests they aren’t, even when they lead to identical amounts of weight loss. Comparing three commonly recommended diet plans, the researchers found that losing weight on any of them improved overall metabolic health in adults with obesity who also had elevated blood sugar and excess fat in their liver – which are important risk factors for developing diabetes. But limiting carbohydrates through a ketogenic diet offered additional benefits for liver health and blood sugar control.

The findings appear August 27 in Cell Metabolism.

“For patients with obesity, prediabetes and fatty liver disease, weight loss induced by a very low-carbohydrate diet provides additional therapeutic effects on glucose and lipid metabolism that should further help prevent the progression to more severe metabolic diseases than weight loss alone,” said Samuel Klein, MD, the Danforth Professor of Medicine and Nutritional Science at WashU Medicine and the study’s senior author. “But all three diets – despite vastly different macronutrient makeups, from very low carbohydrates to very high carbohydrates – successfully improved metabolic health through weight loss alone.”

Which diet best improves metabolic and liver health?

Obesity affects roughly four in 10 Americans, most of whom also face metabolic health risks, including insulin resistance, which leads to prediabetes, and fat buildup in the liver. If left untreated, these problems can progress to Type 2 diabetes, chronic liver disease and cardiovascular events, among other irreversible conditions. While weight loss is the gold standard for reducing obesity-related health risks, it hasn’t been clear which type of diet, in terms of its protein, fat and carb content, works best to improve metabolic health.

To explore that question, the researchers, including first author Max C. Petersen, MD, PhD, an assistant professor of medicine in the John T. Milliken Department of Medicine at WashU Medicine, and Gordon I. Smith, PhD, an associate professor of medicine in the department, randomly assigned 55 adults with metabolically unhealthy obesity – meaning obesity with prediabetes and fatty liver – to follow one of three diets for around five months: a low-carbohydrate, high-fat ketogenic diet; a high-carbohydrate, low-fat, plant-forward diet; or a Mediterranean diet balanced between the two. Participants received 100% of their food throughout the study and attended weekly meetings with a study dietitian to support adherence to the assigned diet.

Across all three groups, participants lost an equal amount of weight, shedding about 10% of their total starting weight, and boosted insulin sensitivity in muscle cells by roughly 50% from baseline. The comparable restoration of insulin sensitivity across diet groups suggests that the weight loss itself was the important factor in combatting muscle insulin resistance – not the combination of fat and carbohydrates used to get there.

“Many metabolically unhealthy patients also are candidates for GLP-1 medicines, which have been very useful tools for helping people lose weight. But our results show that choice of diet remains important because it has an impact on specific health outcomes that go beyond weight loss alone.”

Max C. Petersen, MD, PhD, WashU Medicine

But this wasn’t the case for liver health. The researchers found that sensitivity to insulin in liver cells – which regulates how well the liver suppresses glucose production – improved two to three times more on the ketogenic diet compared with the other diets, though all three groups saw improvement. They also found that the ketogenic diet reduced fat inside the liver by 67% compared to 45% for the other two diets after five months.

“Fatty liver disease affects about 75% of adults with obesity worldwide and has become the fastest-growing cause of chronic liver disease and liver cirrhosis,” said Petersen. “Our study shows that for people with obesity and fatty liver disease, a low-carbohydrate ketogenic diet could help reduce that statistic.”

The ketogenic diet also provided greater improvements in blood sugar control than the other plans did, lowering 24-hour blood glucose measurements by 20% from baseline compared to 8% on the other diets. Insulin levels in the blood throughout the day also decreased by 74% on the low-carbohydrate diet compared to 44% and 27% on the Mediterranean and high-carbohydrate diets, respectively. This sharp decline in insulin reflects the decreased need for insulin to regulate blood glucose when consuming a very-low carbohydrate diet, so the pancreas doesn’t need to overproduce insulin to get a response.

Half of the participants on the low-carbohydrate diet reversed their prediabetes, compared to 29% of participants on the Mediterranean diet and 7% on the high-carbohydrate diet.

“Weight loss – even just a moderate amount – is universally beneficial in people who are metabolically unhealthy,” said Petersen. “Many metabolically unhealthy patients also are candidates for GLP-1 medicines, which have been very useful tools for helping people lose weight. But our results show that choice of diet remains important because it has an impact on specific health outcomes that go beyond weight loss alone.”

In future studies, the researchers are interested in understanding the fundamental mechanisms responsible for the metabolic benefits of weight loss, including the effects of GLP-1 medicines.

Abeeha Shamshad contributed to this story.

Source: University of Washington Medicine

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Scientists Are Discovering Something Surprising About Obesity in Teenagers

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Adolescent metabolism may remain flexible enough for early weight loss interventions to prevent lasting health damage

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Obesity doesn’t look the same at age 15 as it does at age 45 and Duke University School of Medicine researchers are learning why.

A study published in the Journal of Clinical Investigation showed teenagers retain a degree of metabolic flexibility that’s largely lost in adulthood. The study suggests that the way teenage bodies respond to excess weight is fundamentally different and potentially more reversible.

By showing that obesity’s biology changes with age, the discovery points to a potential window when the metabolic damage linked to obesity can be halted, or even reversed, before it becomes a lasting health burden.

“For a long time, medicine has tended to treat adolescents as little adults,” said John Rawls, PhD, a professor of molecular genetics and microbiology and member of the Duke Microbiome Center. “But teenagers are still growing, building muscle and bone, and using energy in ways that are very different from adults. We wanted to understand how those differences shape obesity.”

Nearly 1 in 5 U.S. children has obesity, a condition associated with higher risk for heart disease, diabetes, asthma, and some cancers later in life.

Without intervention, most children with obesity will continue to have obesity into adulthood, said study co-author Sarah Armstrong, MD, a pediatrician and medical weight management specialist at Duke Health.

The change from adolescence to adults happens in late teens to early 20s for women and early-to-mid 20s for men.

But researchers are increasingly asking when those risks become biologically embedded and whether adolescence offers a chance to change course.

The microbiome tells a different story in teens

The Duke team focused on two systems often linked to obesity: the gut microbiome which is the community of microbes living in the digestive tract, and the metabolome, the collection of chemicals produced as the body and microbiome process food and energy.

First, using gut microbes collected from 287 teenagers in the Pediatric Obesity Microbiome and Metabolism Study, they confirmed that teens with obesity have microbiomes that differ compositionally from those of teens at a healthy weight.

Next, Jessica McCann, PhD, a senior research associate in molecular genetics and microbiology, transplanted microbiome samples from adolescents with and without obesity into germ-free mice.

Unlike what researchers often see in adult obesity studies, the mice did not gain extra weight after receiving microbiota from adolescents with obesity.

The findings indicate that while obesity-related differences in the microbiome are beginning to emerge during adolescence, those microbes may not be driving disease the waythey do in adults.

“This suggests there’s a developmental window in which the microbiome becomes involved in obesity,” McCann said. “The relationship between the host and the microbiome may still be developing during adolescence, which means there may be an opportunity to change its trajectory.”

Warning signs appear, but so does resilience

Working in collaboration with the Duke Molecular Physiology Institute, the research team also found differences in how adolescents process nutrients. Adults with obesity often have elevated levels of branched-chain amino acids, as well as related compounds called branched-chain keto acids (BCKA), which are linked with insulin resistance and Type 2 diabetes.

The adolescents showed a different pattern. While branched-chain amino acids were elevated, BCKA levels remained relatively low.

The warning signs are there, McCann said, but teens’ bodies still appear capable of adapting to the metabolic strain of excess weight. “The metabolome is showing early signs of disease progression, but it’s also showing evidence of adaptive plasticity.”

At this stage they may be more responsive to weight management through diet, medication or microbiome-based therapies.

“The evidence increasingly supports intervening as early as possible,” said Armstrong, a professor of pediatrics at Duke.

Researchers hope the work would eventually lead to more personalised obesity treatments, using a child’s microbiome or metabolic profile, to help determine which weight loss therapies are most likely to succeed.

The study was supported by the American Heart Association and the National Institute of Diabetes and Digestive and Kidney Diseases.  

Source: Duke University School of Medicine

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Study Indicates Type 2 Diabetes Operates Differently Across Weight Profiles

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Research published in Diabetologia by Amsterdam UMC and the University of Ghana reveals that type 2 diabetes manifests in two fundamentally different ways depending on a patient’s body mass index (BMI). While type 2 diabetes in patients with a higher BMI is primarily driven by insulin resistance, the study demonstrates that in individuals within a lower BMI range, the condition is caused by the pancreas failing to produce sufficient insulin. Despite these opposing biological mechanisms, medical professionals currently treat both groups with the exact same medications.

Type 2 diabetes is generally seen as a disease associated with being overweight. In wealthy countries that picture holds true: nine out of ten people with type 2 diabetes are overweight. In Africa the situation is different. Almost four in ten African adults with type 2 diabetes are lean, with a normal or even low body weight. In some rural areas, such as in Ghana, it is as many as six in ten. First Author Sabrina Esmail: “This means that there are an estimated ten million lean patients on the African continent who do not fit the standard picture. For them, the problem is therefore a shortage of insulin, not a reduced response to insulin.” Projectleader Charles Agyemang at Amsterdam UMC believes “this study shows that we need to look for better treatments for this large group of lean Africans.”

A different disease process, so a different treatment too

Yet in Africa both groups are almost always given the same treatment, based on international guidelines: oral tablets such as metformin or sulfonylureas. These medicines, however, are mainly effective against insulin resistance, not against a shortage of insulin. They are therefore probably receiving the wrong treatment, and until now the consequences of this had not been investigated. 

The researchers analysed data from more than 3300 African adults with type 2 diabetes from Ghana, Nigeria, Kenya and Europe. “From this we concluded that lean patients more often develop eye damage, known as retinopathy, and strokes. People who are overweight, by contrast, more often have high blood pressure and an increased risk of cardiovascular disease. Chronic kidney disease occurred equally often in both groups,” says senior author Felix Chilunga. The amount of body fat explained the greater part of these differences, which points to genuinely different disease processes. The risk factors differ as well: whereas being overweight is often linked to an unhealthy lifestyle, lean patients have more often experienced malnutrition or a low birth weight, which can disrupt the development of the pancreas.

Type 2 diabetes in lean Africans is therefore, biologically and clinically, a different type of disease from the one seen in people who are overweight. But it is still being treated as though it were the same. As a result, millions of people may not be receiving the right care. Chilunga: “We are calling for targeted clinical trials to determine which treatment works best for this large and often overlooked group of patients.”

Africans in Europe

For Africans in Europe, too, it is very likely that a different treatment is needed. Another study with analysis from data from the UK Biobank showed that people of African descent with a BMI of 26 already have the same diabetes risk as Europeans with a BMI of 30. Studies of migrants in Europe consistently show that Africans are more likely to have type 2 diabetes, develop it around ten years earlier, and have poorer blood sugar control than the native population. Agyemang: “So a considerable proportion of African patients in Europe have a lower BMI but are treated according to guidelines written for the form of the disease found in people who are overweight, and their control is demonstrably worse. There is no reason to assume that the treatment mismatch we describe stops at the border.”

This study was carried out by Amsterdam UMC, University of Ghana, the national Institutes of Health (Center for Research on Genomics and Global Health) via de cohorts AADM and RODAM. The findings were published today in Diabetologia.

Source: Amsterdam UMC

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A Promising New Obesity and Diabetes Treatment Helps Burn Fat While Keeping Muscle

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Over the past five years, medications called GLP-1s have revolutionised the treatment of metabolic disorders like obesity, diabetes and fatty liver diseases. These drugs are highly effective at helping people lose weight and manage their blood sugar levels.

However, they do come with some risks. Some people taking GLP-1s experience nausea and other gastrointestinal side effects that can be difficult to manage. And, by suppressing appetite and reducing food intake, they have the potential to cause nutritional deficiencies and muscle loss, which can lead to frailty and other problems long term. 

At UC Berkeley, researchers have found a new potential treatment for obesity and diabetes that works by increasing energy expenditure – boosting the body’s metabolic rate – rather than limiting energy intake. 

In a study published online in the journal Science Advances, the researchers show that a molecular compound called 5-tetradecyloxy-2-furoic acid (TOFA) is able to block the production of lipids like cholesterol and triglycerides while simultaneously turning up genes that help cells burn fat and generate energy.

In experiments in mice, the researchers found that TOFA is effective at improving insulin sensitivity and glucose control, lowering triglycerides and improving features of fatty liver disease. When obese mice took the compound, they lost weight from fat but experienced no significant loss of lean muscle mass.

“Body weight responds to two levers: taking in fewer calories, or spending more energy,” said Anders Näär, a professor of metabolic biology and nutrition at UC Berkeley and senior author of the study. “GLP-1s work almost entirely on the first, so we went after the second.”

TOFA was first discovered in the 1970s and is known for being part of a class of compounds called ACC inhibitors, which help block the production of lipids in the body. Though several ACC inhibitors reached mid-stage clinical testing, none has been approved for metabolic disease. This is largely because many of these compounds can also raise triglycerides, posing a significant risk to heart health. 

In the new study, the researchers found that TOFA doesn’t just act as an ACC inhibitor, but also activates PPARα and PPARδ, cellular receptors which turn on genes that let cells take up fat and burn it for energy. In mice, this caused the cells to burn up to 18% more energy with no change in physical activity or increase in body temperature. Perhaps because of this dual mechanism, TOFA also did not raise triglycerides like other ACC inhibitors. 

“TOFA appears to engage a coordinated metabolic response,” said study first author Justin Y. Lee, a postdoctoral student at UCSF who conducted the research as a Ph.D. student at Berkeley. “It is not simply blocking lipid synthesis. It is also activating energy expenditure pathways that may help the body handle excess lipid and glucose more effectively.”

When the researchers tried giving mice two separate compounds – one to block lipid production and a second to boost energy expenditure – they found that the combination was not as effective at improving overall metabolic health as TOFA alone. 

The researchers also explored whether TOFA could be used together with GLP-1 medications like semaglutide, which is sold under the brand names Ozempic or Wegovy, and tirzepatide, which is sold as Mounjaro and Zepbound. In mice, they found that combining TOFA with these GLP-1 drugs led to greater improvements in body weight, glucose control, insulin levels and triglycerides than either treatment alone. 

“In our combination experiments, TOFA worked additively or synergistically with the GLP-1 appetite suppressing drugs, so we view it as complementary rather than as a replacement,” Näär said. 

The researchers caution that TOFA has only been studied in animals, and its safety and efficacy in humans has yet to be tested. With support from Berkeley’s life sciences entrepreneurship ecosystem, including Nucleate and Berkeley SkyDeck, they have founded a new company ReRx Therapeutics to help carry this work to patients. 

Source: UC Berkeley

Categories : Ageing Metabolic DisordersTags :

Waist Circumference Raises Mortality Risk in Elderly – Regardless of BMI

On By ModernMedia
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In a Journal of the American Geriatrics Society analysis of nationally representative data from 6905 US adults aged 65 or older followed between 2011–2024, higher body mass index (BMI) was associated with lower mortality risk, whereas higher waist circumference, a marker of abdominal obesity, was independently associated with higher mortality risk after accounting for BMI.

Compared with normal weight, overweight males and males with class I and II obesity (BMI of 30 to less than 40 kg/m2) had 46% and 51% lower risks of mortality, respectively. Additionally, a high waist circumference was also associated with a 24% higher mortality risk in males. Similar patterns were observed in females.

When BMI and waist circumference were evaluated together, being overweight was associated with lower mortality risk regardless of waist circumference among males. Class I and II obesity also remined associated with lower mortality risk exclusively among males with elevated waist circumference. In contrast, being underweight, regardless of waist circumference, and having normal BMI with elevated waist circumference were both associated with higher mortality risk in both males and females.

“BMI and waist circumference provide complementary information about health risk in older adults,” said study co-author, Bryan Blissmer, PhD, of the University of Rhode Island. “Our findings suggest that considering both measures together, rather than relying on BMI alone, may improve mortality risk assessment and support more informed clinical decision-making.”

Source: Wiley