Popular weight-loss drugs to stomach paralysis, other serious gastrointestinal conditions

 They’re being hailed as an effective way to lose weight, but diabetes drugs like Ozempic may come with a heightened risk of severe gastrointestinal problems.

That’s according to new research from the University of British Columbia showing that medications known as GLP-1 agonists—which includes brands like Wegovy, Ozempic, Rybelsus and Saxenda—are associated with an increased risk of serious medical conditions including stomach paralysis, pancreatitis and bowel obstruction.

While previous studies highlighted some of these risks in patients with diabetes, this is the first large, population-level study to examine adverse gastrointestinal events in non-diabetic patients using the drugs specifically for weight loss. The findings were published today in JAMA.

“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss,” said first author Mohit Sodhi, a graduate of UBC’s experimental medicine program and fourth year UBC medical student studying the adverse events of commonly prescribed medications. “The risk calculus will differ depending on whether a patient is using these drugs for diabetes, obesity or just general weight loss. People who are otherwise healthy may be less willing to accept these potentially serious adverse events.”

GLP-1 agonists were originally developed for managing Type 2 diabetes, but exploded in popularity over the past decade as an off-label weight-loss tool, reaching approximately 40 million prescriptions in the U.S. in 2022.

It was only in 2021 that some forms of the medications were approved as a treatment for obesity. However, randomized clinical trials examining the efficacy of the medications for weight loss were not designed to capture rare gastrointestinal events due to their small sample sizes and short follow-up periods.

“There have been anecdotal reports of some patients using these drugs for weight loss and then presenting with repeated episodes of nausea and vomiting secondary to a condition referred to as gastroparesis,” said senior author Dr. Mahyar Etminan, an epidemiologist and associate professor in the department of ophthalmology and visual sciences at the UBC faculty of medicine. “But until now, there hasn’t been any data from large epidemiologic studies.”

To help fill this knowledge gap, UBC researchers examined health insurance claim records for approximately 16 million U.S. patients and looked at people prescribed either semaglutide or liraglutide, two main GLP-1 agonists, between 2006 and 2020. They included patients with a recent history of obesity, and excluded those with diabetes or who had been prescribed another antidiabetic drug.

The researchers analyzed the records to see how many patients developed one of four gastrointestinal conditions, and compared that rate to patients using another weight loss drug, bupropion-naltrexone. Compared to bupropion-naltrexone, GLP-1 agonists were associated with a:

• 9.09 times higher risk of pancreatitis, or inflammation of the pancreas, which can cause severe abdominal pain and, in some cases, require hospitalization and surgery.
• 4.22 times higher risk of bowel obstruction, whereby food is prevented from passing through the small or large intestine, resulting in symptoms like cramping, bloating, nausea and vomiting. Depending on the severity, surgery may be required.
• 3.67 times higher risk of gastroparesis, or stomach paralysis, which limits the passage of food from the stomach to the small intestine and results in symptoms like vomiting, nausea and abdominal pain.

The study also found a higher incidence of biliary disease, a group of conditions affecting the gall bladder, but the difference was not found to be statistically significant.

The researchers say that although the events are rare, with millions around the world using the drugs, it could still lead to hundreds of thousands of people experiencing these conditions.

“These drugs are becoming increasingly accessible, and it is concerning that, in some cases, people can simply go online and order these kinds of medications when they may not have a full understanding of what could potentially happen. This goes directly against the mantra of informed consent,” said Sodhi.

In the meantime, the researchers hope that regulatory agencies and drug makers will consider updating the warning labels for their products, which currently don’t include the risk of gastroparesis.

“This is critical information for patients to know so they can seek timely medical attention and avoid serious consequences,” said Sodhi.

Grape consumption benefits eye health in human study of older adults

 

In a recent randomized, controlled human study, consuming grapes for 16 weeks improved key markers of eye health in older adults.  The study, published in the scientific journal Food & Function looked at the impact of regular consumption of grapes on macular pigment accumulation and other biomarkers of eye health.[1]  This is the first human study on this subject, and the results reinforce earlier, preliminary studies where consuming grapes was found to protect retinal structure and function.[2]  

Science has shown that an aging population has a higher risk of eye disease and vision problems.  Key risk factors for eye disease include 1) oxidative stress and 2) high levels of ocular advanced glycation end products (AGEs).  AGEs may contribute to many eye diseases by damaging the vascular components of the retina, impairing cellular function, and causing oxidative stress.  Dietary antioxidants can decrease oxidative stress and inhibit the formation of AGEs, with possible beneficial effects on the retina, such as an improvement in Macular Pigment Optical Density (MPOD).  Grapes are a natural source of antioxidants and other polyphenols.

In this new study, 34 human subjects consumed either grapes (equivalent to 1 ½ cups of grapes per day) or a placebo for 16 weeks.  The grape eaters showed a significant increase in MPOD, plasma antioxidant capacity, and total phenolic content compared to those on placebo.  Those who didn’t consume grapes saw a significant increase in harmful AGEs, as measured in the skin.

“Our study is the first to show that grape consumption beneficially impacts eye health in humans which is very exciting, especially with a growing aging population,” said Dr. Jung Eun Kim.  “Grapes are an easy, accessible fruit that studies have shown can have a beneficial impact in normal amounts of just 1 ½ cups per day.” 

Metabolically healthy obesity: fact or fiction?

 

A session at this year’s Annual Meeting of the European Association for the Study of Diabetes will explore the latest data on the concept of metabolically healthy obesity (MHO) – more commonly known by the public as ‘fat but fit’. Professor Matthias Blüher, University of Leipzig, Leipzig and Helmholtz Center Munich, Germany  will explain how we define MHO and ask if it can really be described as healthy.

“Some 15-20% of people living with obesity have none of the metabolic complications we associate with the condition, namely abnormal blood sugar control and blood fats, high blood pressure, type 2 diabetes and other signs of cardiovascular disease,” explains Prof Blüher.

Estimates suggest a different prevalence of MHO in men and women, with women living with obesity more likely to have MHO (7-28%) than men (2-19%). At the other end of the spectrum, around half of people living with obesity have at least 2 complications. For a given total body fat mass, people with MHO have lower liver fat mass (thann expected for the BMI and total fat mass).

Prof Blüher will discuss that is how the adipose tissue behaves in people with obesity, rather than their body-mass index, that will determine whether or not their obesity is MHO. In people with adipocytes (fat storing cells) that are of a normal size, those people are less likely to display the complications of obesity – whereas in people with enlarged adipocytes and inflamed adipose tissue, these cells are more likely to exhibit traits such as insulin resistance that lead to metabolic complications.

And the way that we store fat is likely key in whether or not obesity can be described as MHO. “When people with obesity have fat stored viscerally, or internally around their organs (such as in the liver), the data show that these people are much more likely to develop type 2 diabetes than those who store fat more evenly around their body,” says Prof Blüher.

He goes on to explain that in people with adipose tissue dysfunction, this can lead to damaged tissue, fibrosis, secretion of proinflammatory and adipogenic molecules that subsequently contribute to end-organ damage. As an example, adipokines (fat released hormones) may act directly on cells of the vascular system and lead to atherosclerosis. In addition, metabolites such as fatty acids may impair the function of liver or insulin-producing cells in the pancreas.

Finally, on the key question as to whether or not MHO can genuinely be described as healthy, Prof Blüher will explain that several studies show that compared with people of normal weight with no metabolic comorbidities, people living with obesity with no metabolic comorbidities have a 50% increased risk of coronary heart disease. “So there is still a residual increased risk for those people living with obesity, even with what we would call metabolically healthy obesity,” he says.

In conclusion, there are people with obesity that do not exhibit cardio-metabolic complications at a certain point in time. In the past, the diagnosis of MHO frequently led to a low priority for obesity treatment. This concept has been challenged, because recent data suggest that the term metabolically healthy obesity is misleading. He concludes: “Even in the absence of other cardiometabolic risk factors, increased fat mass and adipose tissue dysfunction contribute to a higher risk of type 2 diabetes and cardiovascular diseases. Therefore, weight management and recommendations for weight loss are still important for people living with metabolically healthy obesity.”

Losing sleep? It might be time to check your blood pressure

 

New study from Brigham researchers highlights a correlation between symptoms of insomnia and hypertension in women

Peer-Reviewed Publication

BRIGHAM AND WOMEN'S HOSPITAL

New study from Brigham researchers highlights a correlation between symptoms of insomnia and hypertension in women

Getting enough sleep has never been more difficult in today's fast-paced environment. Yet new research from investigators in the Channing Division of Network Medicine of Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, highlights why getting a good night’s sleep is critical to staying healthy. Their research unveils that women who struggled with getting enough sleep were at greater risk of developing hypertension, or high blood pressure. Results are published in the journal Hypertension.

"These findings suggest that individuals who struggle with symptoms of insomnia may be at risk of hypertension and could benefit from preemptive screening," explained Shahab Haghayegh, Ph.D., a research fellow at the Brigham and Harvard Medical School. "Hypertension is associated with many other physical and mental health complications. The sooner we can identify individuals with high blood pressure and treat them for it, the better we can mitigate future health issues."

Both hypertension and sleep disorders are becoming increasingly prevalent among adults in the United States. In fact, more than 35% of US adults do not get enough sleep at night, according to the Centers for Disease Control and Prevention. The American Academy of Sleep Medicine suggests that 30% of Americans experience symptoms of insomnia. Strikingly, 45% of U.S. adults live with high blood pressure.

Haghayegh and colleagues followed 66,122 participants between 25 and 42 years of age in the Nurses' Health Study II (NHS2) cohort, all without hypertension at the study's onset, over sixteen years (from 2001 until 2017). Investigators collected information on participants’ age, race, body mass index (BMI), diet, lifestyle, physical activity, history of sleep apnea, and family history of hypertension and assessed the incidence of hypertension among the group every two years. They first began measuring sleep duration in 2001, then did so again in 2009, recording the average number of hours slept over a 24-hour period. They also tracked sleeping difficulties, such as having trouble falling or staying asleep or waking up early in the morning, collecting responses at several time points throughout the study. 

Data analyses revealed that women with sleeping difficulties had higher BMIs, lower physical activity, and poorer diets, on average. Researcher also found that those who struggled with sleep were more likely to smoke and drink alcohol and have previously gone through menopause.

Among the 25,987 cases of hypertension documented over the follow-up, women who slept less than seven to eight hours a night had a significantly higher risk of developing hypertension, according to the data collected. Similarly, women who had trouble falling asleep and staying asleep were also more likely to develop hypertension. Waking up early in the morning was not associated with this increased risk. Notably, these associations, remained significant after controlling for participant shift work schedules (night versus day shifts) and chronotype (morningness versus eveningness).

While the exact nature of the relationship between sleep and risk of hypertension is unknown, Haghayegh said that sleep difficulties can lead to a chain of events that can increase sodium retention, arterial stiffness, and cardiac output, potentially leading to hypertension. Disruptions to the sleep/wake cycle can also influence blood vessel constriction/relaxation activity and the function of cells that regulate the vascular tone.

While this study only looked at the association between sleep and hypertension in women, researchers hope to expand their work to include men and non-binary participants. A second limitation is that researchers could only collect data on sleep quality at select time points throughout the study. Some of the study’s strengths include the larger number of participants and length of follow-up duration.

 Haghayegh emphasizes that these findings do not indicate causality. He wants to understand why this association exists and how treating one condition may also treat the other. In future clinical studies, he aims to investigate if sleep medications could have a beneficial effect on blood pressure.

"I hope these findings further underscore the crucial role of quality sleep in our overall well-being. The American Academy of Sleep Medicine recommends sleeping seven or more hours a night, and if you cannot fall or stay asleep, it might be worth exploring why that is," said Haghayegh. "This study highlights yet another reason why getting a good night's sleep is so important."

 

Drinking dark tea every day may help control blood sugar to reduce diabetes risk

Study reveals potential mechanisms behind the benefits of tea drinking in reducing the risk of prediabetes and type 2 diabetes

Reports and Proceedings

DIABETOLOGIA

Drinking dark tea every day may help to mitigate type 2 diabetes risk and progression in adults through better blood sugar control, suggests new research at this year’s Annual Meeting of The European Association for the Study of Diabetes (EASD), Hamburg (2-6 Oct).

The study, by researchers from the University of Adelaide in Australia and Southeast University in China, found that compared with never tea drinkers, daily consumers of dark tea had 53% lower risk for prediabetes and 47% reduced risk for type 2 diabetes, even after taking into account established risk factors known to drive the risk for diabetes, including age, gender, ethnicity, body mass index (BMI), average arterial blood pressure, fasting plasma glucose, cholesterol, alcohol intake, smoking status, family history of diabetes and regular exercise.

“The substantial health benefits of tea, including a reduced risk of cardiovascular disease and type 2 diabetes, have been reported in several studies over recent years, but the mechanisms underlying these benefits have been unclear”, notes the study’s co-lead author Associate Professor Tongzhi Wu from the University of Adelaide and The Hospital Research Foundation Group Mid-Career Fellow.

“Our findings hint at the protective effects of habitual tea drinking on blood sugar management via increased glucose excretion in urine, improved insulin resistance and thus better control of blood sugar. These benefits were most pronounced among daily dark tea drinkers.”

These beneficial effects on metabolic control may lie in the unique way dark tea is produced, which involves microbial fermentation, a process that may yield unique bioactive compounds (including alkaloids, free amino acids, polyphenols, polysaccharides, and their derivatives) to exhibit potent antioxidant and anti-inflammatory effects, improve both insulin sensitivity and the performance of beta cells in the pancreas, and change the composition of the bacteria in the gut.

he latest cross-sectional study included 1,923 adults (562 men,1,361 women aged 20-80 years) living in the community across 8 provinces in China. In total, 436 participants were living with diabetes and 352 with prediabetes, and 1,135 had normal blood glucose levels.

Participants included both non-habitual tea drinkers and those with a history of drinking only a single type of tea. They were asked about the frequency (i.e. never, occasionally, often and every day) and type (i.e. green, black, dark, or other tea) of tea consumption.

The researchers examined the association between both the frequency and type of tea consumption and excretion of glucose in the urine (assessed by the morning spot urine glucose-to-creatine ratio [UGCR]), insulin resistance (measured using the triglyceride and glucose index [TyG] derived from fasting plasma glucose and fasting triglyceride levels), and glycaemic status (defined as a history of type 2 diabetes, current use of antidiabetic medications, or an abnormal 75g oral glucose tolerance test).

People with diabetes often have enhanced capacity for renal glucose reabsorption, so their kidneys retrieve more glucose, preventing it from being excreted in urine, which contributes to the higher blood sugar.

After accounting for differences in age, sex, and clinical and lifestyle factors, the analysis found that drinking tea every day was associated with an increase in urinary glucose excretion (UGCR by 0.11 mmol/mmol) and a reduction in insulin resistance (TyG by -0.23), as well as 15% lower risk for prediabetes and 28% reduced risk for type 2 diabetes, compared with never tea-drinkers.

These favourable health effects were most robust for dark tea drinkers, with consumption of dark tea associated with an increase in UGCR by 0.16 mmol/mmol and a reduction in TyG by 0.31.

According to Associate Professor Wu: “These findings suggest that the actions of bioactive compounds in dark tea may directly or indirectly modulate glucose excretion in the kidneys, an effect, to some extent, mimicking that of sodium-glucose co-transporter-2 (SGLT2) inhibitors, a new anti-diabetic drug class that is not only effective at preventing and treating type 2 diabetes, but also has a substantial protective effects on the heart and kidneys.”

Co-lead author Professor Zilin Sun from Southeast University adds, “Our findings suggest that drinking dark tea every day has the potential to lessen type 2 diabetes risk and progression through better blood sugar control. When you look at all the different biomarkers associated with habitual drinking of dark tea, it may be one simple step people can easily take to improve their diet and health.”

Despite the promising findings, the authors caution that as with any observational study, the findings cannot prove that drinking tea every day improves blood sugar control by increasing urinary glucose excretion and reducing insulin resistance, but suggest that they are likely to contribute. They are currently conducting a double-blind, randomised trial to investigate the benefits of dark tea on blood glucose control in people living with type 2 diabetes to validate their findings. In addition, they cannot rule out the possibility that residual confounding by other lifestyle and physiological factors may have affected the results.

Walking more than five flights of stairs a day can cut risk of heart disease by 20%

Forget walking 10,000 steps a day. Taking at least 50 steps climbing stairs each day could significantly slash your risk of heart disease, according to a new study from Tulane University.

The study, published in Atherosclerosis, found that climbing more than five flights of stairs daily could reduce risk of cardiovascular disease by 20%.

Atherosclerotic cardiovascular disease (ASCVD) along with coronary artery disease and stroke are the leading causes of morbidity and mortality worldwide.

“Short bursts of high-intensity stair climbing are a time-efficient way to improve cardiorespiratory fitness and lipid profile, especially among those unable to achieve the current physical activity recommendations,” said co-corresponding author Dr. Lu Qi, HCA Regents Distinguished Chair and professor at the Tulane University School of Public Health and Tropical Medicine. “These findings highlight the potential advantages of stair climbing as a primary preventive measure for ASCVD in the general population.”

Using UK Biobank data collected from 450,000 adults, the study calculated participants’ susceptibility to cardiovascular disease based on family history, established risk factors and genetic risk factors and surveyed participants about their lifestyle habits and frequency of stair climbing. Median follow-up time was 12.5 years.

The study found that climbing more stairs daily especially reduced risk of cardiovascular disease in those who were less susceptible. However, Qi said the increased risk of heart disease in more susceptible people could be “effectively offset” by daily stair climbing.

Qi touted the public availability of stairs as a low-cost, accessible way to incorporate exercise into daily routines.

“This study provides novel evidence for the protective effects of stair climbing on the risk of ASCVD, particularly for individuals with multiple ASCVD risk factors,” Qi said.

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JOURNAL

Atherosclerosis

DOI

10.1016/j.atherosclerosis.2023.117300 

Study pinpoints the length of incidental activity linked to health benefits

 

Peer-Reviewed Publication

UNIVERSITY OF SYDNEY

A new wearables study tracking over 25,000 people provides the best evidence yet that short bouts of incidental activity, the kind we do as part of daily living, could reduce risk of heart attack, stroke and even premature death – but the length of activity and intensity matters.

“From walking up the stairs to speedily mopping the floors; in recent years we’ve come to understand that it is not just structured exercise that is good for our health, but we know very little about how these short bouts of incidental activity translate to health benefits,” said the study’s senior author Professor Emmanuel Stamatakis from the University of Sydney’s Charles Perkins Centre.

In a study published in The Lancet Public Health today, a University of Sydney led team of international researchers with collaborators from University College London, University of Glasgow, University of Edinburgh, Loughborough University and University of Oxford set out to answer that question.

They used wrist-worn wearables data from the UK Biobank and machine learning to analyse the seven-day incidental physical activity patterns of 25, 241 UK adults aged 42 to 78, down to a 10-second time window. They then linked these physical activity micropatterns with participants' health records, following them for close to eight years to identify how length and intensity of physical activity bouts were linked to health status.

In this cohort of people who self-reported no participation in exercise or sport they found;

• 97% of incidental physical activity was accrued in bouts lasting <10 minutes
• Short bouts of <10 minutes at a moderate to vigorous intensity were associated with a steep decrease in major cardiac events (heart attack/stroke) and death by any cause.
• Moving consistently for at least 1 to 3 minutes was associated with significantly more benefit (29% lower) than very short bouts <1 minute.
• The longer the bouts the better (e.g., accrued in 2 minutes vs 30 seconds), regardless of total activity levels.
• The higher the % of vigorous activity in each bout the better – those who huffed and puffed for at least 15% of the bout (roughly 10 seconds per minute) saw the greatest benefit.
• Bouts <1 minute were also associated with benefits if the above 15% vigorous activity rule was applied.

 

“This study suggests people could potentially reduce their risk of major cardiac events by engaging in daily living activities of at least moderate intensity where they are ideally moving continuously for at least one to three minutes at a time. In fact, it appears that this can have comparable health benefits to longer bouts lasting 5 to 10 minutes,” said lead author Dr Matthew Ahmadi, Postdoctoral Research Fellow at the University of Sydney’s Charles Perkins Centre.

“The take-home message here is any type of activity is good for your health, but the more effort you put into those daily tasks and the longer you keep up that energy, the more benefits you are likely to reap,” said Professor Stamatakis.

“If you are huffing and puffing and unable to hold a conversation for some of that time you have hit the sweet spot.”

The observational nature of the study means researchers cannot prove a cause-and-effect relationship with certainty. However, the researchers made extensive use of the UK Biobank’s baseline health information allowing them to account for a number of factors such as diet, smoking, alcohol consumption, sleep and sedentary time. They also took precautionary measures against the potential effects of reverse causation, whereby poor health may influence activity patterns, by excluding those who had a cardiac event within five years of the wearables measurement, high frailty, and poor self-rated health.

Why do we need to know more about incidental activity?

Fewer than one in five middle-aged adults engage in regular exercise. There are a number of reasons for this including cost, time commitment, health status and access to facilities or infrastructure, but the fact remains that most people are not meeting recommended physical activity guidelines.

“The idea of accruing short bouts of moderate to vigorous activity through daily living activities makes physical activity much more accessible to people who are unwilling or unable to take part in structured exercise,” said Dr Ahmadi. “But as we see in this data, the length and the vigour people put into these incidental activities matters.”

The researchers say the study also provides some of the first direct evidence to support the idea that movement doesn’t have to be completed in continuous 10 minute bouts to be beneficial – a widely held belief until the World Health Organization removed this from their physical activity guidelines in 2020, instead focusing on the idea that ‘every move counts towards better health’. 

The researchers write: “If verified in future research, our findings could inform future public health messaging targeting the general population raising awareness of potential health benefits from short physical activity bouts in everyday life, especially for adults who do not or cannot exercise.”