Clinician Reviews

A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).

Chinese University of Hong Kong

Is there a ‘safe’ dose for glucocorticoids?

To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.

The study was published in Annals of the Rheumatic Diseases.

The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.

University of Wisconsin School of Medicine and Public Health

Long-term glucocorticoid use discouraged

Daily doses of less than 5 mg were not associated with higher MACE risk, but more research is necessary to understand whether these low doses are clinically efficacious, Dr. Tam said. “The study results suggest that a very-low-dose GC (less than 5 mg prednisolone daily) may be cardiovascular risk–neutral. However, further evaluation is needed to determine whether this dose is therapeutic. Other potential side effects, such as bone loss, increased infection risk, dyslipidemia, and hyperglycemia, should also be considered.”

Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology acknowledge that short-term GCs may be necessary for some RA patients, but they emphasize using the smallest necessary dose for the shortest period possible because of the known toxicity of GCs.

“We recommend stopping GCs as soon as it is clinically feasible, in line with previous recommendations, until these issues are investigated further,” Dr. Tam added.

Dr. Bartels agreed that long-term use of GCs should be avoided if possible, even at lower doses, because although CV risk may be less of an issue, studies have shown an increased risk for infection even at GC doses of less than 5 mg a day.
 

How might risk increase with dose?

While the study showed a distinct difference in risk with doses of prednisolone higher and lower than 5 mg, more information on how risk increases with dose could be useful, said Beth Wallace, MD, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center. She was also unaffiliated with the research. “If someone is on 5-10 mg ... how much better is that than being on 10-20 mg or being on 20-30 mg?” she asked. While these study findings are “very important,” she said, it would be useful to know the risk associated with 7.5 mg vs. a higher dose.

University of Michigan

A version of this article first appeared on Medscape.com.

A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).

Chinese University of Hong Kong

Is there a ‘safe’ dose for glucocorticoids?

To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.

The study was published in Annals of the Rheumatic Diseases.

The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.

University of Wisconsin School of Medicine and Public Health

Long-term glucocorticoid use discouraged

Daily doses of less than 5 mg were not associated with higher MACE risk, but more research is necessary to understand whether these low doses are clinically efficacious, Dr. Tam said. “The study results suggest that a very-low-dose GC (less than 5 mg prednisolone daily) may be cardiovascular risk–neutral. However, further evaluation is needed to determine whether this dose is therapeutic. Other potential side effects, such as bone loss, increased infection risk, dyslipidemia, and hyperglycemia, should also be considered.”

Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology acknowledge that short-term GCs may be necessary for some RA patients, but they emphasize using the smallest necessary dose for the shortest period possible because of the known toxicity of GCs.

“We recommend stopping GCs as soon as it is clinically feasible, in line with previous recommendations, until these issues are investigated further,” Dr. Tam added.

Dr. Bartels agreed that long-term use of GCs should be avoided if possible, even at lower doses, because although CV risk may be less of an issue, studies have shown an increased risk for infection even at GC doses of less than 5 mg a day.
 

How might risk increase with dose?

While the study showed a distinct difference in risk with doses of prednisolone higher and lower than 5 mg, more information on how risk increases with dose could be useful, said Beth Wallace, MD, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center. She was also unaffiliated with the research. “If someone is on 5-10 mg ... how much better is that than being on 10-20 mg or being on 20-30 mg?” she asked. While these study findings are “very important,” she said, it would be useful to know the risk associated with 7.5 mg vs. a higher dose.

University of Michigan

A version of this article first appeared on Medscape.com.

A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).

Chinese University of Hong Kong

Is there a ‘safe’ dose for glucocorticoids?

To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.

The study was published in Annals of the Rheumatic Diseases.

The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.

University of Wisconsin School of Medicine and Public Health

Long-term glucocorticoid use discouraged

Daily doses of less than 5 mg were not associated with higher MACE risk, but more research is necessary to understand whether these low doses are clinically efficacious, Dr. Tam said. “The study results suggest that a very-low-dose GC (less than 5 mg prednisolone daily) may be cardiovascular risk–neutral. However, further evaluation is needed to determine whether this dose is therapeutic. Other potential side effects, such as bone loss, increased infection risk, dyslipidemia, and hyperglycemia, should also be considered.”

Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology acknowledge that short-term GCs may be necessary for some RA patients, but they emphasize using the smallest necessary dose for the shortest period possible because of the known toxicity of GCs.

“We recommend stopping GCs as soon as it is clinically feasible, in line with previous recommendations, until these issues are investigated further,” Dr. Tam added.

Dr. Bartels agreed that long-term use of GCs should be avoided if possible, even at lower doses, because although CV risk may be less of an issue, studies have shown an increased risk for infection even at GC doses of less than 5 mg a day.
 

How might risk increase with dose?

While the study showed a distinct difference in risk with doses of prednisolone higher and lower than 5 mg, more information on how risk increases with dose could be useful, said Beth Wallace, MD, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center. She was also unaffiliated with the research. “If someone is on 5-10 mg ... how much better is that than being on 10-20 mg or being on 20-30 mg?” she asked. While these study findings are “very important,” she said, it would be useful to know the risk associated with 7.5 mg vs. a higher dose.

University of Michigan

A version of this article first appeared on Medscape.com.

Public perception of disease is everything. “Diabetics” are now referred to as “people living with diabetes,” and an “obese person” is now an “individual living with obesity.”

But what is the definition of obesity? Does it refer to a disease or a risk factor? And is the term so tainted in negativity, blame, and bias that the only solution is to scrap it and completely rename it? Society (and medicine) have changed significantly since the Latin word obesitas was adopted back in the 1600s.

Despite so much hinging on the word “obesity,” it’s remarkable that the label persists while the concepts underpinning it have evolved significantly. So perhaps it is more about finding the least-worst option rather than pursuing the impossibility of a solution that suits all?

This is precisely the challenge faced by a Lancet Diabetes & Endocrinology Commission on the Definition and Diagnosis of Clinical Obesity, which is due to publish its initial findings this coming fall. The global task force has 60 leaders in the clinical management of obesity, including representatives with lived experiences of obesity. Leading the project is Francesco Rubino, MD, chair of metabolic and bariatric surgery at King’s College London.

“Renaming ‘obesity’ is very important,” states Dr. Rubino. “The word is so stigmatized, with so much misunderstanding and misperception, some might say the only solution is to change the name.”

One possibility for a new name, introduced by the American Association of Clinical Endocrinologists (now –Endocrinology) and the American College of Endocrinology back in 2016, was based on framing the disease on the central characteristic of adiposity and was termed ABCD, for adiposity-based chronic disease.

Dr. Rubino welcomes “ABCD” but has some reservations. “It is good from a physiological point of view, but the problem is it speaks to scientists and medical professionals. I don’t know how much it would appeal to the general public. ‘ABCD’ still falls short of telling us what the illness is.”

He adds that the Lancet Commission’s approach is rather to call it “clinical obesity.” “ ‘Obesity’ itself doesn’t necessarily convey the message that you have a disease or an illness,” he observes. “It is similar to the difference in meaning between depression and clinical depression, which communicate two different things.”

But underpinning any renaming is greater clarification of the definition and diagnosis of obesity. In 1997, the World Health Organization recognized obesity as a chronic disease; in 2013, the American Medical Association did likewise, adding that it warranted medical attention; while it took until 2021 for the European Commission to define obesity as a “chronic relapsing disease, which in turn acts as a gateway to a range of other non-communicable diseases.”

Yet, 25 years after the initial recognition of obesity as a disease, the concept is still riddled with negativity, whether openly or unconsciously. Such stigma denigrates overweight people and those with obesity as “lazy, sloppy, unintelligent, and unattractive.”

Dr. Rubino explains that first, it’s important to establish and define the essential components and characteristics of the disease of obesity. This is key to improving access to clinical care, reducing personal blame, and nurturing a more supportive research environment to help inform both clinical and policy decision-making.

“This is the question that is at the core of our commission. We have a problem with the current definition of obesity, and the way we measure it does not allow us to accurately define a state of illness with obesity,” he explains.
 

Labels shape public perceptions of disease; ‘obesity’ epitomizes this

Another expert championing the need for a name that better reflects the definition – whatever that turns out to be – is Margaret Steele, PhD, School of Public Health, University College Cork (Ireland), who, according to her university webpage, has a special interest in “ ‘fatness’ as a cultural, social and political phenomenon.”

She believes that labels, including “obesity,” have a pivotal role in shaping public perceptions. In our digital, information-rich age, the boundaries of medicine and society overlap, with public perception shaping decisions of a medical nature as never before. But with this comes controversy and division – obesity management being a case in point.

Specifically, the word “obesity” is too widely associated with negative connotations, she says, and therefore she welcomes the dialogue around redefining and renaming it. Despite wide general support for a name and definition that reflects adiposity, due to its central physiologic role in the complications of obesity, Dr. Steele believes that the “effects on adipose tissue are downstream of brain issues and the food environment,” and she wants to see more attention brought to this.

Referring to most Westernized societies, she describes how people who grew up in times of food scarcity, before processed foods became widely available, have a different taste profile from those who grew up afterwards. “Growing up in 1940s and ‘50s Ireland, people recall how they remember getting an orange as a treat at Christmas, because the idea that you could have food all year-round – any fruit and veg that you want, when you want it – just wasn’t there.”

By comparison, societal changes leading to more financial and time pressure in later decades meant that fast, high-fat, high-sugar, and processed foods became more desirable, she points out. “Most young children now recognize the company name, and even the specific fast-food brand [they like], before they know their alphabet.”

The current environment has cultivated “a very different physical reaction to foods, maybe a different kind of emotional response,” she believes, highlighting the tightly woven relationship between obesity, society, mental health, and food options.

Dr. Steele wants to stimulate a conversation about the term used to describe individuals, conventionally described as ‘”obese” or using the word “obesity.” “We’re thinking in terms of maybe chronic appetite, chronic food intake, or dietary intake dysregulation.”

Changing medical terminology when it has become useless or harmful is not new, she argues, with co-author, Francis Finucane, MD, consultant endocrinologist at Galway University Hospitals, Ireland, in a recent paper on the subject.

“In the 20th century, the terms ‘feeble-minded’ and ‘moron’ had become used in a pejorative way in the wider culture and were dropped from medical usage,” Dr. Steele points out. She adds that changing the term “obesity” can facilitate pursuit of the strategic goals of clinical medicine “without causing needless controversy with those who, given their own goals and contexts, understand body mass index or body weight in a radically different way.”
 

Obesity: Disease, risk factor, or both?

Dr. Rubino stresses that prior to any renaming, there is a need to establish and define the essential components and characteristics of the disease of obesity. “This question is at the core of our Commission, and it is not an easy conversation to have.” He further explains that the struggle with the current definition of obesity, and the way it is conceived, is largely centered on it still being considered a risk factor for something else.

Disease is characterized by three things, says Dr. Rubino. These comprise the phenomenon of having a pathogenic cause, leading to pathophysiologic alterations (of the organs), causing clinical manifestations.

He adds that obesity is currently described by what it can cause – for example, type 2 diabetes, cancer, or hypertension. “Each of these things have their own clinical manifestations but obesity doesn’t. [As a disease], we don’t have a definition of the clinical manifestations of obesity other than excess adiposity.”

“If we use BMI, this does not predict excess adiposity, nor does it determine a disease here and now. There is no disease without an illness, which is the clinical manifestation, and the perception by the patient of it being an illness,” explains Dr. Rubino, pointing out that the Lancet Commission is filling this gap in knowledge by asking, “If obesity is an illness, then what does it look like?”

He adds that waist circumference probably provides a better measure than BMI in directly indicating the abnormal distribution of adiposity, known to be associated with poor cardiometabolic outcomes, “but it doesn’t tell you if you have an illness here and now – only that someone is at risk of developing cardiovascular disease in the future. Most people with some excess fat around the waist are perfectly functional and don’t feel ill.”

He also explains that confusion persists around whether obesity – or excess adiposity – is a risk factor for or a symptom of another disease. “The picture is blurred, and we do not know how to discriminate between these. We only have one name, and it applies to all those things, and we have one criterion – BMI – to diagnose it!”

Dr. Rubino adds, “So, what defines it? Is it diabetes? No, because that is another disease. You don’t define a disease by another. It has to stand on its own.”

Recently, the American Medical Association advised that BMI now be used in conjunction with other valid measures of risk such as, but not limited to, measurements of visceral fat, body adiposity index, body composition, relative fat mass, waist circumference, and genetic/metabolic factors.

Aayush Visaria, MD, an internal medicine resident at Rutgers University, New Brunswick, New Jersey, agrees that a new name might help change public perception of obesity for the better. A study he presented at the 2023 Endocrine Society Meeting found that BMI “vastly underestimates” obesity.

He agrees with Dr. Rubino that the challenge lies in the lack of precise understanding of the mechanisms driving obesity: “It’s multifactorial, so not just appetite or food intake. Putting this into one phrase is difficult.”

However, if a new term can incorporate the many facets of the disease, “overall, it’ll reduce stigma because we’ll start to think about obesity as a disease process, not a personal thing with blame attached,” says Dr. Visaria.

But simultaneously, he expresses caution around possible negative connotations associated with the classification of obesity as a disease. Dr. Steele also reflects on this risk, highlighting that medicalizing body size can be counterproductive in feeding into weight stigma and fatphobia.

“Medicalizing obesity can be discouraging rather than empowering, but by specifying more clearly that we’re talking about a specific set of interrelated metabolic conditions, it would make it much clearer, and that ... this isn’t about making people skinny, it isn’t about an aesthetic thing,” Dr. Steele observes.
 

The word ‘obesity’ hinders disease explanations

Dr. Steele explains that her goal is to overcome the ambiguity around the word “obesity” that hinders explanations of the disease of obesity to the wider public.

“Much confusion and controversy might be avoided if we were to clarify that when doctors say that obesity is a disease, they do not mean that being ‘fat’ is a disease.”

Nevertheless, adipose tissue is an active endocrine organ, producing hormones that function less well in people with obesity, she notes. “This new knowledge has led to better treatments, including drugs like semaglutide and tirzepatide. These drugs, like bariatric surgery, typically lead to significant weight loss and to improvements in overall metabolic health.”

Dr. Rubino also expresses concerns around medicalization, as determined by definition and diagnosis and the availability of drug treatment that could potentially lead to overtreatment. “Currently, when everyone with a BMI of greater than 30 gets access to every obesity treatment out there, we see drugs are running out of stock. We should prioritize that treatment.”

Ultimately, the diagnosis of obesity as a disease needs an anthropometric biomarker that provides, on an individual level, the confidence that a person has a disease today, or at least close to a 100% likelihood of developing this disease and illness, asserts Dr. Rubino.

“If we use BMI, or even waist circumference, these might diagnose the disease; but if the person lives to 90 years, what’s the point of labeling somebody as having an illness?” he points out.

“As doctors, we have to be cautious. We say this is a disease, but you must think about the implications for the person on the receiving end of that diagnosis of a chronic disease that is substantially incurable. When we say it, we need to be certain.”

Dr. Steele and Dr. Visaria have disclosed no relevant financial relationships. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, Metadeq, GHP Scientific, and ViBo Health for no remuneration.

A version of this article first appeared on Medscape.com.

Public perception of disease is everything. “Diabetics” are now referred to as “people living with diabetes,” and an “obese person” is now an “individual living with obesity.”

But what is the definition of obesity? Does it refer to a disease or a risk factor? And is the term so tainted in negativity, blame, and bias that the only solution is to scrap it and completely rename it? Society (and medicine) have changed significantly since the Latin word obesitas was adopted back in the 1600s.

Despite so much hinging on the word “obesity,” it’s remarkable that the label persists while the concepts underpinning it have evolved significantly. So perhaps it is more about finding the least-worst option rather than pursuing the impossibility of a solution that suits all?

This is precisely the challenge faced by a Lancet Diabetes & Endocrinology Commission on the Definition and Diagnosis of Clinical Obesity, which is due to publish its initial findings this coming fall. The global task force has 60 leaders in the clinical management of obesity, including representatives with lived experiences of obesity. Leading the project is Francesco Rubino, MD, chair of metabolic and bariatric surgery at King’s College London.

“Renaming ‘obesity’ is very important,” states Dr. Rubino. “The word is so stigmatized, with so much misunderstanding and misperception, some might say the only solution is to change the name.”

One possibility for a new name, introduced by the American Association of Clinical Endocrinologists (now –Endocrinology) and the American College of Endocrinology back in 2016, was based on framing the disease on the central characteristic of adiposity and was termed ABCD, for adiposity-based chronic disease.

Dr. Rubino welcomes “ABCD” but has some reservations. “It is good from a physiological point of view, but the problem is it speaks to scientists and medical professionals. I don’t know how much it would appeal to the general public. ‘ABCD’ still falls short of telling us what the illness is.”

He adds that the Lancet Commission’s approach is rather to call it “clinical obesity.” “ ‘Obesity’ itself doesn’t necessarily convey the message that you have a disease or an illness,” he observes. “It is similar to the difference in meaning between depression and clinical depression, which communicate two different things.”

But underpinning any renaming is greater clarification of the definition and diagnosis of obesity. In 1997, the World Health Organization recognized obesity as a chronic disease; in 2013, the American Medical Association did likewise, adding that it warranted medical attention; while it took until 2021 for the European Commission to define obesity as a “chronic relapsing disease, which in turn acts as a gateway to a range of other non-communicable diseases.”

Yet, 25 years after the initial recognition of obesity as a disease, the concept is still riddled with negativity, whether openly or unconsciously. Such stigma denigrates overweight people and those with obesity as “lazy, sloppy, unintelligent, and unattractive.”

Dr. Rubino explains that first, it’s important to establish and define the essential components and characteristics of the disease of obesity. This is key to improving access to clinical care, reducing personal blame, and nurturing a more supportive research environment to help inform both clinical and policy decision-making.

“This is the question that is at the core of our commission. We have a problem with the current definition of obesity, and the way we measure it does not allow us to accurately define a state of illness with obesity,” he explains.
 

Labels shape public perceptions of disease; ‘obesity’ epitomizes this

Another expert championing the need for a name that better reflects the definition – whatever that turns out to be – is Margaret Steele, PhD, School of Public Health, University College Cork (Ireland), who, according to her university webpage, has a special interest in “ ‘fatness’ as a cultural, social and political phenomenon.”

She believes that labels, including “obesity,” have a pivotal role in shaping public perceptions. In our digital, information-rich age, the boundaries of medicine and society overlap, with public perception shaping decisions of a medical nature as never before. But with this comes controversy and division – obesity management being a case in point.

Specifically, the word “obesity” is too widely associated with negative connotations, she says, and therefore she welcomes the dialogue around redefining and renaming it. Despite wide general support for a name and definition that reflects adiposity, due to its central physiologic role in the complications of obesity, Dr. Steele believes that the “effects on adipose tissue are downstream of brain issues and the food environment,” and she wants to see more attention brought to this.

Referring to most Westernized societies, she describes how people who grew up in times of food scarcity, before processed foods became widely available, have a different taste profile from those who grew up afterwards. “Growing up in 1940s and ‘50s Ireland, people recall how they remember getting an orange as a treat at Christmas, because the idea that you could have food all year-round – any fruit and veg that you want, when you want it – just wasn’t there.”

By comparison, societal changes leading to more financial and time pressure in later decades meant that fast, high-fat, high-sugar, and processed foods became more desirable, she points out. “Most young children now recognize the company name, and even the specific fast-food brand [they like], before they know their alphabet.”

The current environment has cultivated “a very different physical reaction to foods, maybe a different kind of emotional response,” she believes, highlighting the tightly woven relationship between obesity, society, mental health, and food options.

Dr. Steele wants to stimulate a conversation about the term used to describe individuals, conventionally described as ‘”obese” or using the word “obesity.” “We’re thinking in terms of maybe chronic appetite, chronic food intake, or dietary intake dysregulation.”

Changing medical terminology when it has become useless or harmful is not new, she argues, with co-author, Francis Finucane, MD, consultant endocrinologist at Galway University Hospitals, Ireland, in a recent paper on the subject.

“In the 20th century, the terms ‘feeble-minded’ and ‘moron’ had become used in a pejorative way in the wider culture and were dropped from medical usage,” Dr. Steele points out. She adds that changing the term “obesity” can facilitate pursuit of the strategic goals of clinical medicine “without causing needless controversy with those who, given their own goals and contexts, understand body mass index or body weight in a radically different way.”
 

Obesity: Disease, risk factor, or both?

Dr. Rubino stresses that prior to any renaming, there is a need to establish and define the essential components and characteristics of the disease of obesity. “This question is at the core of our Commission, and it is not an easy conversation to have.” He further explains that the struggle with the current definition of obesity, and the way it is conceived, is largely centered on it still being considered a risk factor for something else.

Disease is characterized by three things, says Dr. Rubino. These comprise the phenomenon of having a pathogenic cause, leading to pathophysiologic alterations (of the organs), causing clinical manifestations.

He adds that obesity is currently described by what it can cause – for example, type 2 diabetes, cancer, or hypertension. “Each of these things have their own clinical manifestations but obesity doesn’t. [As a disease], we don’t have a definition of the clinical manifestations of obesity other than excess adiposity.”

“If we use BMI, this does not predict excess adiposity, nor does it determine a disease here and now. There is no disease without an illness, which is the clinical manifestation, and the perception by the patient of it being an illness,” explains Dr. Rubino, pointing out that the Lancet Commission is filling this gap in knowledge by asking, “If obesity is an illness, then what does it look like?”

He adds that waist circumference probably provides a better measure than BMI in directly indicating the abnormal distribution of adiposity, known to be associated with poor cardiometabolic outcomes, “but it doesn’t tell you if you have an illness here and now – only that someone is at risk of developing cardiovascular disease in the future. Most people with some excess fat around the waist are perfectly functional and don’t feel ill.”

He also explains that confusion persists around whether obesity – or excess adiposity – is a risk factor for or a symptom of another disease. “The picture is blurred, and we do not know how to discriminate between these. We only have one name, and it applies to all those things, and we have one criterion – BMI – to diagnose it!”

Dr. Rubino adds, “So, what defines it? Is it diabetes? No, because that is another disease. You don’t define a disease by another. It has to stand on its own.”

Recently, the American Medical Association advised that BMI now be used in conjunction with other valid measures of risk such as, but not limited to, measurements of visceral fat, body adiposity index, body composition, relative fat mass, waist circumference, and genetic/metabolic factors.

Aayush Visaria, MD, an internal medicine resident at Rutgers University, New Brunswick, New Jersey, agrees that a new name might help change public perception of obesity for the better. A study he presented at the 2023 Endocrine Society Meeting found that BMI “vastly underestimates” obesity.

He agrees with Dr. Rubino that the challenge lies in the lack of precise understanding of the mechanisms driving obesity: “It’s multifactorial, so not just appetite or food intake. Putting this into one phrase is difficult.”

However, if a new term can incorporate the many facets of the disease, “overall, it’ll reduce stigma because we’ll start to think about obesity as a disease process, not a personal thing with blame attached,” says Dr. Visaria.

But simultaneously, he expresses caution around possible negative connotations associated with the classification of obesity as a disease. Dr. Steele also reflects on this risk, highlighting that medicalizing body size can be counterproductive in feeding into weight stigma and fatphobia.

“Medicalizing obesity can be discouraging rather than empowering, but by specifying more clearly that we’re talking about a specific set of interrelated metabolic conditions, it would make it much clearer, and that ... this isn’t about making people skinny, it isn’t about an aesthetic thing,” Dr. Steele observes.
 

The word ‘obesity’ hinders disease explanations

Dr. Steele explains that her goal is to overcome the ambiguity around the word “obesity” that hinders explanations of the disease of obesity to the wider public.

“Much confusion and controversy might be avoided if we were to clarify that when doctors say that obesity is a disease, they do not mean that being ‘fat’ is a disease.”

Nevertheless, adipose tissue is an active endocrine organ, producing hormones that function less well in people with obesity, she notes. “This new knowledge has led to better treatments, including drugs like semaglutide and tirzepatide. These drugs, like bariatric surgery, typically lead to significant weight loss and to improvements in overall metabolic health.”

Dr. Rubino also expresses concerns around medicalization, as determined by definition and diagnosis and the availability of drug treatment that could potentially lead to overtreatment. “Currently, when everyone with a BMI of greater than 30 gets access to every obesity treatment out there, we see drugs are running out of stock. We should prioritize that treatment.”

Ultimately, the diagnosis of obesity as a disease needs an anthropometric biomarker that provides, on an individual level, the confidence that a person has a disease today, or at least close to a 100% likelihood of developing this disease and illness, asserts Dr. Rubino.

“If we use BMI, or even waist circumference, these might diagnose the disease; but if the person lives to 90 years, what’s the point of labeling somebody as having an illness?” he points out.

“As doctors, we have to be cautious. We say this is a disease, but you must think about the implications for the person on the receiving end of that diagnosis of a chronic disease that is substantially incurable. When we say it, we need to be certain.”

Dr. Steele and Dr. Visaria have disclosed no relevant financial relationships. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, Metadeq, GHP Scientific, and ViBo Health for no remuneration.

A version of this article first appeared on Medscape.com.

Public perception of disease is everything. “Diabetics” are now referred to as “people living with diabetes,” and an “obese person” is now an “individual living with obesity.”

But what is the definition of obesity? Does it refer to a disease or a risk factor? And is the term so tainted in negativity, blame, and bias that the only solution is to scrap it and completely rename it? Society (and medicine) have changed significantly since the Latin word obesitas was adopted back in the 1600s.

Despite so much hinging on the word “obesity,” it’s remarkable that the label persists while the concepts underpinning it have evolved significantly. So perhaps it is more about finding the least-worst option rather than pursuing the impossibility of a solution that suits all?

This is precisely the challenge faced by a Lancet Diabetes & Endocrinology Commission on the Definition and Diagnosis of Clinical Obesity, which is due to publish its initial findings this coming fall. The global task force has 60 leaders in the clinical management of obesity, including representatives with lived experiences of obesity. Leading the project is Francesco Rubino, MD, chair of metabolic and bariatric surgery at King’s College London.

“Renaming ‘obesity’ is very important,” states Dr. Rubino. “The word is so stigmatized, with so much misunderstanding and misperception, some might say the only solution is to change the name.”

One possibility for a new name, introduced by the American Association of Clinical Endocrinologists (now –Endocrinology) and the American College of Endocrinology back in 2016, was based on framing the disease on the central characteristic of adiposity and was termed ABCD, for adiposity-based chronic disease.

Dr. Rubino welcomes “ABCD” but has some reservations. “It is good from a physiological point of view, but the problem is it speaks to scientists and medical professionals. I don’t know how much it would appeal to the general public. ‘ABCD’ still falls short of telling us what the illness is.”

He adds that the Lancet Commission’s approach is rather to call it “clinical obesity.” “ ‘Obesity’ itself doesn’t necessarily convey the message that you have a disease or an illness,” he observes. “It is similar to the difference in meaning between depression and clinical depression, which communicate two different things.”

But underpinning any renaming is greater clarification of the definition and diagnosis of obesity. In 1997, the World Health Organization recognized obesity as a chronic disease; in 2013, the American Medical Association did likewise, adding that it warranted medical attention; while it took until 2021 for the European Commission to define obesity as a “chronic relapsing disease, which in turn acts as a gateway to a range of other non-communicable diseases.”

Yet, 25 years after the initial recognition of obesity as a disease, the concept is still riddled with negativity, whether openly or unconsciously. Such stigma denigrates overweight people and those with obesity as “lazy, sloppy, unintelligent, and unattractive.”

Dr. Rubino explains that first, it’s important to establish and define the essential components and characteristics of the disease of obesity. This is key to improving access to clinical care, reducing personal blame, and nurturing a more supportive research environment to help inform both clinical and policy decision-making.

“This is the question that is at the core of our commission. We have a problem with the current definition of obesity, and the way we measure it does not allow us to accurately define a state of illness with obesity,” he explains.
 

Labels shape public perceptions of disease; ‘obesity’ epitomizes this

Another expert championing the need for a name that better reflects the definition – whatever that turns out to be – is Margaret Steele, PhD, School of Public Health, University College Cork (Ireland), who, according to her university webpage, has a special interest in “ ‘fatness’ as a cultural, social and political phenomenon.”

She believes that labels, including “obesity,” have a pivotal role in shaping public perceptions. In our digital, information-rich age, the boundaries of medicine and society overlap, with public perception shaping decisions of a medical nature as never before. But with this comes controversy and division – obesity management being a case in point.

Specifically, the word “obesity” is too widely associated with negative connotations, she says, and therefore she welcomes the dialogue around redefining and renaming it. Despite wide general support for a name and definition that reflects adiposity, due to its central physiologic role in the complications of obesity, Dr. Steele believes that the “effects on adipose tissue are downstream of brain issues and the food environment,” and she wants to see more attention brought to this.

Referring to most Westernized societies, she describes how people who grew up in times of food scarcity, before processed foods became widely available, have a different taste profile from those who grew up afterwards. “Growing up in 1940s and ‘50s Ireland, people recall how they remember getting an orange as a treat at Christmas, because the idea that you could have food all year-round – any fruit and veg that you want, when you want it – just wasn’t there.”

By comparison, societal changes leading to more financial and time pressure in later decades meant that fast, high-fat, high-sugar, and processed foods became more desirable, she points out. “Most young children now recognize the company name, and even the specific fast-food brand [they like], before they know their alphabet.”

The current environment has cultivated “a very different physical reaction to foods, maybe a different kind of emotional response,” she believes, highlighting the tightly woven relationship between obesity, society, mental health, and food options.

Dr. Steele wants to stimulate a conversation about the term used to describe individuals, conventionally described as ‘”obese” or using the word “obesity.” “We’re thinking in terms of maybe chronic appetite, chronic food intake, or dietary intake dysregulation.”

Changing medical terminology when it has become useless or harmful is not new, she argues, with co-author, Francis Finucane, MD, consultant endocrinologist at Galway University Hospitals, Ireland, in a recent paper on the subject.

“In the 20th century, the terms ‘feeble-minded’ and ‘moron’ had become used in a pejorative way in the wider culture and were dropped from medical usage,” Dr. Steele points out. She adds that changing the term “obesity” can facilitate pursuit of the strategic goals of clinical medicine “without causing needless controversy with those who, given their own goals and contexts, understand body mass index or body weight in a radically different way.”
 

Obesity: Disease, risk factor, or both?

Dr. Rubino stresses that prior to any renaming, there is a need to establish and define the essential components and characteristics of the disease of obesity. “This question is at the core of our Commission, and it is not an easy conversation to have.” He further explains that the struggle with the current definition of obesity, and the way it is conceived, is largely centered on it still being considered a risk factor for something else.

Disease is characterized by three things, says Dr. Rubino. These comprise the phenomenon of having a pathogenic cause, leading to pathophysiologic alterations (of the organs), causing clinical manifestations.

He adds that obesity is currently described by what it can cause – for example, type 2 diabetes, cancer, or hypertension. “Each of these things have their own clinical manifestations but obesity doesn’t. [As a disease], we don’t have a definition of the clinical manifestations of obesity other than excess adiposity.”

“If we use BMI, this does not predict excess adiposity, nor does it determine a disease here and now. There is no disease without an illness, which is the clinical manifestation, and the perception by the patient of it being an illness,” explains Dr. Rubino, pointing out that the Lancet Commission is filling this gap in knowledge by asking, “If obesity is an illness, then what does it look like?”

He adds that waist circumference probably provides a better measure than BMI in directly indicating the abnormal distribution of adiposity, known to be associated with poor cardiometabolic outcomes, “but it doesn’t tell you if you have an illness here and now – only that someone is at risk of developing cardiovascular disease in the future. Most people with some excess fat around the waist are perfectly functional and don’t feel ill.”

He also explains that confusion persists around whether obesity – or excess adiposity – is a risk factor for or a symptom of another disease. “The picture is blurred, and we do not know how to discriminate between these. We only have one name, and it applies to all those things, and we have one criterion – BMI – to diagnose it!”

Dr. Rubino adds, “So, what defines it? Is it diabetes? No, because that is another disease. You don’t define a disease by another. It has to stand on its own.”

Recently, the American Medical Association advised that BMI now be used in conjunction with other valid measures of risk such as, but not limited to, measurements of visceral fat, body adiposity index, body composition, relative fat mass, waist circumference, and genetic/metabolic factors.

Aayush Visaria, MD, an internal medicine resident at Rutgers University, New Brunswick, New Jersey, agrees that a new name might help change public perception of obesity for the better. A study he presented at the 2023 Endocrine Society Meeting found that BMI “vastly underestimates” obesity.

He agrees with Dr. Rubino that the challenge lies in the lack of precise understanding of the mechanisms driving obesity: “It’s multifactorial, so not just appetite or food intake. Putting this into one phrase is difficult.”

However, if a new term can incorporate the many facets of the disease, “overall, it’ll reduce stigma because we’ll start to think about obesity as a disease process, not a personal thing with blame attached,” says Dr. Visaria.

But simultaneously, he expresses caution around possible negative connotations associated with the classification of obesity as a disease. Dr. Steele also reflects on this risk, highlighting that medicalizing body size can be counterproductive in feeding into weight stigma and fatphobia.

“Medicalizing obesity can be discouraging rather than empowering, but by specifying more clearly that we’re talking about a specific set of interrelated metabolic conditions, it would make it much clearer, and that ... this isn’t about making people skinny, it isn’t about an aesthetic thing,” Dr. Steele observes.
 

The word ‘obesity’ hinders disease explanations

Dr. Steele explains that her goal is to overcome the ambiguity around the word “obesity” that hinders explanations of the disease of obesity to the wider public.

“Much confusion and controversy might be avoided if we were to clarify that when doctors say that obesity is a disease, they do not mean that being ‘fat’ is a disease.”

Nevertheless, adipose tissue is an active endocrine organ, producing hormones that function less well in people with obesity, she notes. “This new knowledge has led to better treatments, including drugs like semaglutide and tirzepatide. These drugs, like bariatric surgery, typically lead to significant weight loss and to improvements in overall metabolic health.”

Dr. Rubino also expresses concerns around medicalization, as determined by definition and diagnosis and the availability of drug treatment that could potentially lead to overtreatment. “Currently, when everyone with a BMI of greater than 30 gets access to every obesity treatment out there, we see drugs are running out of stock. We should prioritize that treatment.”

Ultimately, the diagnosis of obesity as a disease needs an anthropometric biomarker that provides, on an individual level, the confidence that a person has a disease today, or at least close to a 100% likelihood of developing this disease and illness, asserts Dr. Rubino.

“If we use BMI, or even waist circumference, these might diagnose the disease; but if the person lives to 90 years, what’s the point of labeling somebody as having an illness?” he points out.

“As doctors, we have to be cautious. We say this is a disease, but you must think about the implications for the person on the receiving end of that diagnosis of a chronic disease that is substantially incurable. When we say it, we need to be certain.”

Dr. Steele and Dr. Visaria have disclosed no relevant financial relationships. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, Metadeq, GHP Scientific, and ViBo Health for no remuneration.

A version of this article first appeared on Medscape.com.

The annual probability of a person with overweight or obesity losing at least 5% of their body weight is about 1 in 10, while weight loss to a healthy category is even less common, new research finds.

On the brighter side, those with higher body mass index (BMI) had greater odds of losing at least 5% of body weight than those with lower BMI, and women were more likely to do so than men. The chances of achieving a healthy weight category – defined as BMI of 18.5-24.9 kg/m² – was less likely than losing 5% in all groups, however.

Even a modest 5% weight loss at any BMI has been associated with improved health measures, including lower systolic and diastolic blood pressure, lower fasting glucose level, lower hemoglobin A1c level, and higher HDL cholesterol level, write Lyudmyla Kompaniyets, PhD, of the National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and colleagues.

The data from more than 18 million U.S. adults from a nationwide ambulatory electronic medical record database, called IQVIA, suggest that “clinicians and public health efforts can focus on messaging and referrals to interventions that support individuals with excess weight in achieving and sustaining meaningful weight loss, i.e., ≥ 5% for adults at any level of excess weight,” the authors say.

The study population was health care–seeking but not necessarily for weight loss, and their intent to lose weight was unknown. “Several studies suggest that persons who are trying to lose weight may experience greater reductions in weight,” the researchers point out in their article, which was published in JAMA Network Open.

At the initial visit, 72.5% of the participants were categorized as having either overweight (BMI, 25.0-29.9kg/m²) or obesity (BMI, ≥ 30.0 kg/m²). The median age of the patients was 54 years. A little over half (56.7%) were women, 72.3% were White, and 7.7% were Black.

During a maximum follow-up period of 14 years, the proportion with 5% or greater weight loss was 33.4% of those with initial overweight and 41.8% with initial obesity. The proportion achieving healthy weight (BMI, 18.5-24.9 kg/m²) was just 23.2% and 2.0%, respectively.

For the combined overweight/obesity groups, the adjusted annual probability of 5% or greater weight loss was 1 in 10, increasing with BMI category from 1 in 12 for those with initial overweight to 1 in 6 for those with initial BMI of 45 kg/m² or higher. The annual probability was slightly lower among Black than White women (1 in 9 vs. 1 in 8, respectively).

In contrast, the adjusted annual probability of reducing BMI to the healthy category ranged from 1 in 19 with initial overweight to 1 in 1,667 with initial BMI of 45 kg/m² or higher. This probability was higher among women than men and was highest among White women.

“These findings could, in part, be explained by barriers in availability of and access to obesity management options, including lifestyle interventions and pharmacotherapy. There is a continual need for policies and strategies that ensure community access to nutrition and physical activity opportunities,” Dr. Kompaniyets and colleague write.

Moreover, they say, “understanding patterns of weight loss could help support populations, including Hispanic or Latino and non-Hispanic Black individuals, who are disproportionately affected by obesity due to factors such as structural racism and race and ethnicity-based social and economic disadvantages.”

The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The annual probability of a person with overweight or obesity losing at least 5% of their body weight is about 1 in 10, while weight loss to a healthy category is even less common, new research finds.

On the brighter side, those with higher body mass index (BMI) had greater odds of losing at least 5% of body weight than those with lower BMI, and women were more likely to do so than men. The chances of achieving a healthy weight category – defined as BMI of 18.5-24.9 kg/m² – was less likely than losing 5% in all groups, however.

Even a modest 5% weight loss at any BMI has been associated with improved health measures, including lower systolic and diastolic blood pressure, lower fasting glucose level, lower hemoglobin A1c level, and higher HDL cholesterol level, write Lyudmyla Kompaniyets, PhD, of the National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and colleagues.

The data from more than 18 million U.S. adults from a nationwide ambulatory electronic medical record database, called IQVIA, suggest that “clinicians and public health efforts can focus on messaging and referrals to interventions that support individuals with excess weight in achieving and sustaining meaningful weight loss, i.e., ≥ 5% for adults at any level of excess weight,” the authors say.

The study population was health care–seeking but not necessarily for weight loss, and their intent to lose weight was unknown. “Several studies suggest that persons who are trying to lose weight may experience greater reductions in weight,” the researchers point out in their article, which was published in JAMA Network Open.

At the initial visit, 72.5% of the participants were categorized as having either overweight (BMI, 25.0-29.9kg/m²) or obesity (BMI, ≥ 30.0 kg/m²). The median age of the patients was 54 years. A little over half (56.7%) were women, 72.3% were White, and 7.7% were Black.

During a maximum follow-up period of 14 years, the proportion with 5% or greater weight loss was 33.4% of those with initial overweight and 41.8% with initial obesity. The proportion achieving healthy weight (BMI, 18.5-24.9 kg/m²) was just 23.2% and 2.0%, respectively.

For the combined overweight/obesity groups, the adjusted annual probability of 5% or greater weight loss was 1 in 10, increasing with BMI category from 1 in 12 for those with initial overweight to 1 in 6 for those with initial BMI of 45 kg/m² or higher. The annual probability was slightly lower among Black than White women (1 in 9 vs. 1 in 8, respectively).

In contrast, the adjusted annual probability of reducing BMI to the healthy category ranged from 1 in 19 with initial overweight to 1 in 1,667 with initial BMI of 45 kg/m² or higher. This probability was higher among women than men and was highest among White women.

“These findings could, in part, be explained by barriers in availability of and access to obesity management options, including lifestyle interventions and pharmacotherapy. There is a continual need for policies and strategies that ensure community access to nutrition and physical activity opportunities,” Dr. Kompaniyets and colleague write.

Moreover, they say, “understanding patterns of weight loss could help support populations, including Hispanic or Latino and non-Hispanic Black individuals, who are disproportionately affected by obesity due to factors such as structural racism and race and ethnicity-based social and economic disadvantages.”

The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The annual probability of a person with overweight or obesity losing at least 5% of their body weight is about 1 in 10, while weight loss to a healthy category is even less common, new research finds.

On the brighter side, those with higher body mass index (BMI) had greater odds of losing at least 5% of body weight than those with lower BMI, and women were more likely to do so than men. The chances of achieving a healthy weight category – defined as BMI of 18.5-24.9 kg/m² – was less likely than losing 5% in all groups, however.

Even a modest 5% weight loss at any BMI has been associated with improved health measures, including lower systolic and diastolic blood pressure, lower fasting glucose level, lower hemoglobin A1c level, and higher HDL cholesterol level, write Lyudmyla Kompaniyets, PhD, of the National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and colleagues.

The data from more than 18 million U.S. adults from a nationwide ambulatory electronic medical record database, called IQVIA, suggest that “clinicians and public health efforts can focus on messaging and referrals to interventions that support individuals with excess weight in achieving and sustaining meaningful weight loss, i.e., ≥ 5% for adults at any level of excess weight,” the authors say.

The study population was health care–seeking but not necessarily for weight loss, and their intent to lose weight was unknown. “Several studies suggest that persons who are trying to lose weight may experience greater reductions in weight,” the researchers point out in their article, which was published in JAMA Network Open.

At the initial visit, 72.5% of the participants were categorized as having either overweight (BMI, 25.0-29.9kg/m²) or obesity (BMI, ≥ 30.0 kg/m²). The median age of the patients was 54 years. A little over half (56.7%) were women, 72.3% were White, and 7.7% were Black.

During a maximum follow-up period of 14 years, the proportion with 5% or greater weight loss was 33.4% of those with initial overweight and 41.8% with initial obesity. The proportion achieving healthy weight (BMI, 18.5-24.9 kg/m²) was just 23.2% and 2.0%, respectively.

For the combined overweight/obesity groups, the adjusted annual probability of 5% or greater weight loss was 1 in 10, increasing with BMI category from 1 in 12 for those with initial overweight to 1 in 6 for those with initial BMI of 45 kg/m² or higher. The annual probability was slightly lower among Black than White women (1 in 9 vs. 1 in 8, respectively).

In contrast, the adjusted annual probability of reducing BMI to the healthy category ranged from 1 in 19 with initial overweight to 1 in 1,667 with initial BMI of 45 kg/m² or higher. This probability was higher among women than men and was highest among White women.

“These findings could, in part, be explained by barriers in availability of and access to obesity management options, including lifestyle interventions and pharmacotherapy. There is a continual need for policies and strategies that ensure community access to nutrition and physical activity opportunities,” Dr. Kompaniyets and colleague write.

Moreover, they say, “understanding patterns of weight loss could help support populations, including Hispanic or Latino and non-Hispanic Black individuals, who are disproportionately affected by obesity due to factors such as structural racism and race and ethnicity-based social and economic disadvantages.”

The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Brisbane, Australia – Most cases of virologic failure on dolutegravir treatment for HIV are likely due to adherence problems and more time on treatment is needed before switching to another drug, according to new data from the ADVANCE trial.
 

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” said Andrew Hill, MD, from the department of pharmacology and therapeutics at the University of Liverpool, England.

The new data was presented here at the International AIDS Society conference on HIV Science. The ADVANCE trial is a three-arm randomized study involving 1,053 treatment-naive individuals comparing two triple-therapy combinations — dolutegravir, emtricitabine, and one of two tenofovir prodrugs – with a standard care regimen of tenofovir disoproxil fumarate, emtricitabine, and efavirenz.

Although the usual approach for someone in a clinical trial who experiences elevations in HIV RNA levels while on a dolutegravir-based treatment is to switch them to another therapy, the ADVANCE investigators opted for a different strategy.

“We actually continued treatment despite high viral load, and we didn’t have standard discontinuation preferences,” Dr. Hill said at the meeting. They instead provided counseling about adherence, which gave an opportunity to examine viral resuppression rates in participants in both the dolutegravir and efavirenz arms.

This revealed that 95% of patients in the two dolutegravir arms of the study were able to achieve resuppression of their viral load – defined as below 50 viral RNA copies per mL – without any emergence of resistance.
 

The guidelines

Current World Health Organization guidelines recommend that anyone whose viral load goes above 1,000 copies per mL who is on a non-nucleoside reverse transcriptase inhibitor such as efavirenz should be switched to an appropriate regimen.

Those who experience viremia on an integrase inhibitor such as dolutegravir should receive adherence counseling, have a repeat viral load test done in 3 months, and – if their viral load is still elevated – be switched to another regimen.

Dr. Hill and his team were examining how this might play out in a clinical trial setting and they found that there were a similar number of episodes of initial virologic failure in both the dolutegravir and efavirenz groups.

But after adherence counseling, testing for resistance and – if no resistance was evident – continuation with treatment, they saw differences emerge between the two groups.

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” he said.
 

Time to viral resuppression

At 24 weeks after restarting treatment, 88% of people in the dolutegravir group had resuppressed their viral RNA, compared with 46% of people in the efavirenz group. At 48 weeks, those figures were 95% and 66%, respectively.

Dr. Hill pointed out that a significant number of people were lost to follow-up after virologic failure, and genotyping was not performed at baseline.

We addressed the question of how much adherence counseling should be undertaken in people who experienced viremia while on dolutegravir therapy, Dr. Hill said, particularly as there were often very good reasons for lack of adherence, such as homelessness.

“If you can get through those difficult phases, people can go back on their meds,” he said in an interview. “It’s almost a sociological problem rather than a clinical issue.”

And with efavirenz and the lower rates of resuppression observed in the study, Dr. Hill said it was a more fragile drug, so viremia therefore provided the opportunity for resistance to emerge, “and then once the resistant virus is there, you can’t get virus undetectable.”

Laura Waters, MD, a genitourinary and HIV medicine consultant at the Mortimer Market Centre in London, who was not involved in the study, said the results support recommendations to give people on drugs such as dolutegravir, which have a high genetic barrier to resistance, more time to improve their adherence before switching to another therapy.

“Although it provides that reassuring proof of concept, it doesn’t negate the importance of having to continue to monitor, because nothing is infallible,” she told this news organization. “We’ve talked about high-barrier drugs in the past, and you do start seeing resistance emerge.”

A version of this article first appeared on Medscape.com.

Brisbane, Australia – Most cases of virologic failure on dolutegravir treatment for HIV are likely due to adherence problems and more time on treatment is needed before switching to another drug, according to new data from the ADVANCE trial.
 

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” said Andrew Hill, MD, from the department of pharmacology and therapeutics at the University of Liverpool, England.

The new data was presented here at the International AIDS Society conference on HIV Science. The ADVANCE trial is a three-arm randomized study involving 1,053 treatment-naive individuals comparing two triple-therapy combinations — dolutegravir, emtricitabine, and one of two tenofovir prodrugs – with a standard care regimen of tenofovir disoproxil fumarate, emtricitabine, and efavirenz.

Although the usual approach for someone in a clinical trial who experiences elevations in HIV RNA levels while on a dolutegravir-based treatment is to switch them to another therapy, the ADVANCE investigators opted for a different strategy.

“We actually continued treatment despite high viral load, and we didn’t have standard discontinuation preferences,” Dr. Hill said at the meeting. They instead provided counseling about adherence, which gave an opportunity to examine viral resuppression rates in participants in both the dolutegravir and efavirenz arms.

This revealed that 95% of patients in the two dolutegravir arms of the study were able to achieve resuppression of their viral load – defined as below 50 viral RNA copies per mL – without any emergence of resistance.
 

The guidelines

Current World Health Organization guidelines recommend that anyone whose viral load goes above 1,000 copies per mL who is on a non-nucleoside reverse transcriptase inhibitor such as efavirenz should be switched to an appropriate regimen.

Those who experience viremia on an integrase inhibitor such as dolutegravir should receive adherence counseling, have a repeat viral load test done in 3 months, and – if their viral load is still elevated – be switched to another regimen.

Dr. Hill and his team were examining how this might play out in a clinical trial setting and they found that there were a similar number of episodes of initial virologic failure in both the dolutegravir and efavirenz groups.

But after adherence counseling, testing for resistance and – if no resistance was evident – continuation with treatment, they saw differences emerge between the two groups.

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” he said.
 

Time to viral resuppression

At 24 weeks after restarting treatment, 88% of people in the dolutegravir group had resuppressed their viral RNA, compared with 46% of people in the efavirenz group. At 48 weeks, those figures were 95% and 66%, respectively.

Dr. Hill pointed out that a significant number of people were lost to follow-up after virologic failure, and genotyping was not performed at baseline.

We addressed the question of how much adherence counseling should be undertaken in people who experienced viremia while on dolutegravir therapy, Dr. Hill said, particularly as there were often very good reasons for lack of adherence, such as homelessness.

“If you can get through those difficult phases, people can go back on their meds,” he said in an interview. “It’s almost a sociological problem rather than a clinical issue.”

And with efavirenz and the lower rates of resuppression observed in the study, Dr. Hill said it was a more fragile drug, so viremia therefore provided the opportunity for resistance to emerge, “and then once the resistant virus is there, you can’t get virus undetectable.”

Laura Waters, MD, a genitourinary and HIV medicine consultant at the Mortimer Market Centre in London, who was not involved in the study, said the results support recommendations to give people on drugs such as dolutegravir, which have a high genetic barrier to resistance, more time to improve their adherence before switching to another therapy.

“Although it provides that reassuring proof of concept, it doesn’t negate the importance of having to continue to monitor, because nothing is infallible,” she told this news organization. “We’ve talked about high-barrier drugs in the past, and you do start seeing resistance emerge.”

A version of this article first appeared on Medscape.com.

Brisbane, Australia – Most cases of virologic failure on dolutegravir treatment for HIV are likely due to adherence problems and more time on treatment is needed before switching to another drug, according to new data from the ADVANCE trial.
 

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” said Andrew Hill, MD, from the department of pharmacology and therapeutics at the University of Liverpool, England.

The new data was presented here at the International AIDS Society conference on HIV Science. The ADVANCE trial is a three-arm randomized study involving 1,053 treatment-naive individuals comparing two triple-therapy combinations — dolutegravir, emtricitabine, and one of two tenofovir prodrugs – with a standard care regimen of tenofovir disoproxil fumarate, emtricitabine, and efavirenz.

Although the usual approach for someone in a clinical trial who experiences elevations in HIV RNA levels while on a dolutegravir-based treatment is to switch them to another therapy, the ADVANCE investigators opted for a different strategy.

“We actually continued treatment despite high viral load, and we didn’t have standard discontinuation preferences,” Dr. Hill said at the meeting. They instead provided counseling about adherence, which gave an opportunity to examine viral resuppression rates in participants in both the dolutegravir and efavirenz arms.

This revealed that 95% of patients in the two dolutegravir arms of the study were able to achieve resuppression of their viral load – defined as below 50 viral RNA copies per mL – without any emergence of resistance.
 

The guidelines

Current World Health Organization guidelines recommend that anyone whose viral load goes above 1,000 copies per mL who is on a non-nucleoside reverse transcriptase inhibitor such as efavirenz should be switched to an appropriate regimen.

Those who experience viremia on an integrase inhibitor such as dolutegravir should receive adherence counseling, have a repeat viral load test done in 3 months, and – if their viral load is still elevated – be switched to another regimen.

Dr. Hill and his team were examining how this might play out in a clinical trial setting and they found that there were a similar number of episodes of initial virologic failure in both the dolutegravir and efavirenz groups.

But after adherence counseling, testing for resistance and – if no resistance was evident – continuation with treatment, they saw differences emerge between the two groups.

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” he said.
 

Time to viral resuppression

At 24 weeks after restarting treatment, 88% of people in the dolutegravir group had resuppressed their viral RNA, compared with 46% of people in the efavirenz group. At 48 weeks, those figures were 95% and 66%, respectively.

Dr. Hill pointed out that a significant number of people were lost to follow-up after virologic failure, and genotyping was not performed at baseline.

We addressed the question of how much adherence counseling should be undertaken in people who experienced viremia while on dolutegravir therapy, Dr. Hill said, particularly as there were often very good reasons for lack of adherence, such as homelessness.

“If you can get through those difficult phases, people can go back on their meds,” he said in an interview. “It’s almost a sociological problem rather than a clinical issue.”

And with efavirenz and the lower rates of resuppression observed in the study, Dr. Hill said it was a more fragile drug, so viremia therefore provided the opportunity for resistance to emerge, “and then once the resistant virus is there, you can’t get virus undetectable.”

Laura Waters, MD, a genitourinary and HIV medicine consultant at the Mortimer Market Centre in London, who was not involved in the study, said the results support recommendations to give people on drugs such as dolutegravir, which have a high genetic barrier to resistance, more time to improve their adherence before switching to another therapy.

“Although it provides that reassuring proof of concept, it doesn’t negate the importance of having to continue to monitor, because nothing is infallible,” she told this news organization. “We’ve talked about high-barrier drugs in the past, and you do start seeing resistance emerge.”

A version of this article first appeared on Medscape.com.

Brisbane, Australia – Concerns about lower lymphocyte levels in HIV with the once-daily oral drug islatravir in combination with doravirine changed the trajectory of clinical trial plans that are now back on track, according to investigators.

The nucleoside reverse transcriptase translocation inhibitor hit a roadblock in December 2021 when the U.S. Food and Drug Administration put a hold on investigational new drug applications for both the oral and implant formulations of islatravir after some patients in clinical trials showed decreases in total lymphocyte and CD4+ cell counts.

A phase 3, double-blind, randomized, controlled trial was underway at the time of once-daily islatravir (0.75 mg) in combination with 100 mg doravirine, compared with bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) as initial therapy for HIV infection in treatment-naïve individuals. Recruitment was stopped, 83 participants short of the planned 680, but the trial could continue the full 48 weeks.

Jürgen Rockstroh, MD, professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn, Germany, presented the latest results from that trial of 597 patients at the International AIDS Society conference on HIV Science.

At week 48 after starting therapy, 88.9% of participants in the islatravir and doravirine arm and 88.3% of patients in the B/F/TAF arm achieved the primary outcome of HIV-1 RNA levels below 50 copies/mL.

One patient treated with islatravir and doravirine and four patients taking B/F/TAF experienced virologic failure.

Dr. Rockstroh told the conference the patient who developed viremia with the new islatravir combination had very high viral load at baseline but showed a rapid response to treatment, which reduced his viral load down to around 1,200 copies/mL by week 4.

However, by week 24, his islatravir concentration had reduced below detectable levels, suggesting a problem with adherence. His viral load increased again, and three treatment-resistant mutations were detected.

While both arms of the study showed a significant increase in CD4+ T cell counts, Dr. Rockstroh pointed out that some individuals in the islatravir and doravirine arm had a lower absolute increase in lymphocyte counts at week 48.

Overall, the mean change in CD4+ T cell counts was 182 cells/mL in the islatravir and doravirine group, compared with 234 cells/mL in the B/F/TAF group.

More patients in the islatravir combination arm discontinued treatment due to a decrease in CD4+ T cell or total lymphocyte counts – 5.4%, compared with 2% in the B/F/TAF arm, however.

“These changes in lymphocyte counts did not lead to any difference in the amount of infection-related adverse events, which happened in both arms in relatively comparable percentages,” Dr. Rockstroh said at the conference.
 

New lower dose

Because of persistent concerns about the impact on CD4+ T cells and total lymphocytes, Dr. Rockstroh said another phase 3 trial is now underway using a lower 0.25 mg dose of islatravir, again combined with 100 mg doravirine, in people who are treatment-naïve and virologically suppressed.

The study also examined the impact of both treatments on weight gain and found the mean change in weight was similar between both arms – 3.45 kg gain in those on islatravir with doravirine and 3.32 kg gain in those on B/F/TAF, which was not significantly different.

There are several important reasons it is a good idea to have more treatment options available for people with HIV, Dr. Rockstroh said in an interview.

With integrase inhibitors potentially interfering with metabolic health, weight gain, hypertension, insulin resistance, and possible diabetes, “I think it’s wise that we at least have alternative strategies,” he said.

James McMahon, MD, PhD, an infectious diseases physician and head of the Infectious Diseases Clinical Research Unit at the Alfred Hospital and Monash University in Melbourne, said there is always a need for new HIV treatments, particularly ones that are more powerful.

“Whenever you get a drug that’s potent at low dose, it means you can have smaller pills, [and] you can then consider giving more of it in long-acting formulations,” Dr. McMahon said.

He pointed out that the study did not show any signal of increased infections with the lower CD4+ T cell counts in the islatravir and doravirine arm, “but that difference is enough to raise that concern that it’s not ideal, and it should be moved forward with a lower dose, which is what they’ve done.”

A version of this article first appeared on Medscape.com.

Brisbane, Australia – Concerns about lower lymphocyte levels in HIV with the once-daily oral drug islatravir in combination with doravirine changed the trajectory of clinical trial plans that are now back on track, according to investigators.

The nucleoside reverse transcriptase translocation inhibitor hit a roadblock in December 2021 when the U.S. Food and Drug Administration put a hold on investigational new drug applications for both the oral and implant formulations of islatravir after some patients in clinical trials showed decreases in total lymphocyte and CD4+ cell counts.

A phase 3, double-blind, randomized, controlled trial was underway at the time of once-daily islatravir (0.75 mg) in combination with 100 mg doravirine, compared with bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) as initial therapy for HIV infection in treatment-naïve individuals. Recruitment was stopped, 83 participants short of the planned 680, but the trial could continue the full 48 weeks.

Jürgen Rockstroh, MD, professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn, Germany, presented the latest results from that trial of 597 patients at the International AIDS Society conference on HIV Science.

At week 48 after starting therapy, 88.9% of participants in the islatravir and doravirine arm and 88.3% of patients in the B/F/TAF arm achieved the primary outcome of HIV-1 RNA levels below 50 copies/mL.

One patient treated with islatravir and doravirine and four patients taking B/F/TAF experienced virologic failure.

Dr. Rockstroh told the conference the patient who developed viremia with the new islatravir combination had very high viral load at baseline but showed a rapid response to treatment, which reduced his viral load down to around 1,200 copies/mL by week 4.

However, by week 24, his islatravir concentration had reduced below detectable levels, suggesting a problem with adherence. His viral load increased again, and three treatment-resistant mutations were detected.

While both arms of the study showed a significant increase in CD4+ T cell counts, Dr. Rockstroh pointed out that some individuals in the islatravir and doravirine arm had a lower absolute increase in lymphocyte counts at week 48.

Overall, the mean change in CD4+ T cell counts was 182 cells/mL in the islatravir and doravirine group, compared with 234 cells/mL in the B/F/TAF group.

More patients in the islatravir combination arm discontinued treatment due to a decrease in CD4+ T cell or total lymphocyte counts – 5.4%, compared with 2% in the B/F/TAF arm, however.

“These changes in lymphocyte counts did not lead to any difference in the amount of infection-related adverse events, which happened in both arms in relatively comparable percentages,” Dr. Rockstroh said at the conference.
 

New lower dose

Because of persistent concerns about the impact on CD4+ T cells and total lymphocytes, Dr. Rockstroh said another phase 3 trial is now underway using a lower 0.25 mg dose of islatravir, again combined with 100 mg doravirine, in people who are treatment-naïve and virologically suppressed.

The study also examined the impact of both treatments on weight gain and found the mean change in weight was similar between both arms – 3.45 kg gain in those on islatravir with doravirine and 3.32 kg gain in those on B/F/TAF, which was not significantly different.

There are several important reasons it is a good idea to have more treatment options available for people with HIV, Dr. Rockstroh said in an interview.

With integrase inhibitors potentially interfering with metabolic health, weight gain, hypertension, insulin resistance, and possible diabetes, “I think it’s wise that we at least have alternative strategies,” he said.

James McMahon, MD, PhD, an infectious diseases physician and head of the Infectious Diseases Clinical Research Unit at the Alfred Hospital and Monash University in Melbourne, said there is always a need for new HIV treatments, particularly ones that are more powerful.

“Whenever you get a drug that’s potent at low dose, it means you can have smaller pills, [and] you can then consider giving more of it in long-acting formulations,” Dr. McMahon said.

He pointed out that the study did not show any signal of increased infections with the lower CD4+ T cell counts in the islatravir and doravirine arm, “but that difference is enough to raise that concern that it’s not ideal, and it should be moved forward with a lower dose, which is what they’ve done.”

A version of this article first appeared on Medscape.com.

Brisbane, Australia – Concerns about lower lymphocyte levels in HIV with the once-daily oral drug islatravir in combination with doravirine changed the trajectory of clinical trial plans that are now back on track, according to investigators.

The nucleoside reverse transcriptase translocation inhibitor hit a roadblock in December 2021 when the U.S. Food and Drug Administration put a hold on investigational new drug applications for both the oral and implant formulations of islatravir after some patients in clinical trials showed decreases in total lymphocyte and CD4+ cell counts.

A phase 3, double-blind, randomized, controlled trial was underway at the time of once-daily islatravir (0.75 mg) in combination with 100 mg doravirine, compared with bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) as initial therapy for HIV infection in treatment-naïve individuals. Recruitment was stopped, 83 participants short of the planned 680, but the trial could continue the full 48 weeks.

Jürgen Rockstroh, MD, professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn, Germany, presented the latest results from that trial of 597 patients at the International AIDS Society conference on HIV Science.

At week 48 after starting therapy, 88.9% of participants in the islatravir and doravirine arm and 88.3% of patients in the B/F/TAF arm achieved the primary outcome of HIV-1 RNA levels below 50 copies/mL.

One patient treated with islatravir and doravirine and four patients taking B/F/TAF experienced virologic failure.

Dr. Rockstroh told the conference the patient who developed viremia with the new islatravir combination had very high viral load at baseline but showed a rapid response to treatment, which reduced his viral load down to around 1,200 copies/mL by week 4.

However, by week 24, his islatravir concentration had reduced below detectable levels, suggesting a problem with adherence. His viral load increased again, and three treatment-resistant mutations were detected.

While both arms of the study showed a significant increase in CD4+ T cell counts, Dr. Rockstroh pointed out that some individuals in the islatravir and doravirine arm had a lower absolute increase in lymphocyte counts at week 48.

Overall, the mean change in CD4+ T cell counts was 182 cells/mL in the islatravir and doravirine group, compared with 234 cells/mL in the B/F/TAF group.

More patients in the islatravir combination arm discontinued treatment due to a decrease in CD4+ T cell or total lymphocyte counts – 5.4%, compared with 2% in the B/F/TAF arm, however.

“These changes in lymphocyte counts did not lead to any difference in the amount of infection-related adverse events, which happened in both arms in relatively comparable percentages,” Dr. Rockstroh said at the conference.
 

New lower dose

Because of persistent concerns about the impact on CD4+ T cells and total lymphocytes, Dr. Rockstroh said another phase 3 trial is now underway using a lower 0.25 mg dose of islatravir, again combined with 100 mg doravirine, in people who are treatment-naïve and virologically suppressed.

The study also examined the impact of both treatments on weight gain and found the mean change in weight was similar between both arms – 3.45 kg gain in those on islatravir with doravirine and 3.32 kg gain in those on B/F/TAF, which was not significantly different.

There are several important reasons it is a good idea to have more treatment options available for people with HIV, Dr. Rockstroh said in an interview.

With integrase inhibitors potentially interfering with metabolic health, weight gain, hypertension, insulin resistance, and possible diabetes, “I think it’s wise that we at least have alternative strategies,” he said.

James McMahon, MD, PhD, an infectious diseases physician and head of the Infectious Diseases Clinical Research Unit at the Alfred Hospital and Monash University in Melbourne, said there is always a need for new HIV treatments, particularly ones that are more powerful.

“Whenever you get a drug that’s potent at low dose, it means you can have smaller pills, [and] you can then consider giving more of it in long-acting formulations,” Dr. McMahon said.

He pointed out that the study did not show any signal of increased infections with the lower CD4+ T cell counts in the islatravir and doravirine arm, “but that difference is enough to raise that concern that it’s not ideal, and it should be moved forward with a lower dose, which is what they’ve done.”

A version of this article first appeared on Medscape.com.

Obesity, in and of itself, and independent of other cardiovascular risk factors, may cause changes to the heart that can lead to sudden cardiac death, a new case-control study suggests.

Researchers who analyzed hearts taken at autopsy from people who had died from sudden cardiac death found that a number of the hearts obtained from obese decedents were heavier than those from normal-weight decedents and that the hazard ratio of unexplained cardiomegaly in this cohort was 5.3, compared with normal-weight individuals.

“Even when we ruled out any conditions that could potentially cause enlargement of the heart, including hypertension, heart valve problems, diabetes, and other cardiovascular risk factors, the association with obesity cardiomyopathy, or OCM, and sudden cardiac death remained,” lead author Joseph Westaby, PhD, from the Cardiac Risk in the Young (CRY) Cardiovascular Pathology Laboratories at St George’s University of London, said in an interview.

The study was published online in JACC: Advances.

Intrigued by this finding, Dr. Westaby and associates sought to characterize the clinical and pathological features of OCM associated with sudden cardiac death by comparing this population to two control groups: sudden cardiac death patients who were either obese or of normal weight, and had morphologically normal hearts.

Their group is uniquely positioned to do such research, Dr. Westaby explained.

“Here at St George’s University of London, we have a specialized cardiovascular pathology service. ... All hearts obtained at autopsy from individuals who have died from sudden cardiac death, or who were suspected to have had a cardiovascular cause of death, anywhere in the U.K., are referred to the CRY Centre for further analysis,” he said.

Patients were divided into two groups according to body mass index: an obesity group (BMI > 30 kg/m²) and a normal-weight group (BMI, 18.5-24.9).

An increased heart weight above 550 g in men and 450 g in women in the absence of coronary artery disease, hypertension, diabetes, or valvular disease was classified as unexplained cardiomegaly, and individuals with obesity and cardiomegaly were defined as obesity cardiomyopathy.

Age- and sex-matched controls with obesity (n = 106) were selected based on a BMI greater than 30, with a morphologically normal heart weighing less than 550 g in men and than 450 g in women. 

Age- and sex-matched normal weight controls (n = 106) were selected based on a BMI of 18.5-24.9 and a morphologically normal heart weighing less than 550 g in men and less than 450 g in women. 

The researchers identified 53 OCM cases from a cohort of more than 4,500 sudden cardiac death cases that had BMI measurements. In normal-weight patients, there were 14 cases of unexplained cardiomegaly.

The mean age at death of individuals with OCM was 42 years (range, 30-54 years). Most of the deaths occurred in men (n = 34; 64%), who also died younger than women (40 ± 13 years vs. 45 ± 10 years; P = .036).

The average heart weight in OCM patients was 598 ± 93 g. Risk of sudden cardiac death increased when BMI reached 35.

Compared with matched controls, there were increases in right and left ventricular wall thickness (all P < .05) in OCM cases. Right ventricular epicardial fat was increased in OCM cases, compared with normal-weight controls only.

Left ventricular fibrosis was identified in seven (13%) OCM cases.
 

Role of genetics to be explored

“This study highlights the need for further investigation into these individuals because, at the moment, we can’t be sure that the only contributing factor to this is the obesity,” said Dr. Westaby.

In the works are plans to see if there may be an underlying genetic predisposition in obese individuals that may have contributed to the development of an enlarged heart. The group also plans to study the families of the deceased individuals to determine if they are at risk of developing cardiomegaly, he said.

“This paper makes an important contribution to the literature that raises many important questions for future research,” Timothy P. Fitzgibbons, MD, PhD, from the University of Massachusetts, Worcester, wrote in an accompanying editorial.

Being able to access so many autopsy samples gives the current study considerable heft, Dr. Fitzgibbons said in an interview.

“A lot has been made of the obesity paradox and the perhaps benign nature of obesity but this paper suggests the opposite, that it is a very serious problem and can, in fact, in and of itself, cause heart abnormalities that could cause sudden death,” he noted.

The fact that only 13% of OCM cases had fibrosis on histology suggests that fibrosis was not the main cause of sudden cardiac death, he said.

“Often we will do MRIs to look for areas of fibrosis within the heart because those areas make patients prone to re-entry arrhythmias, in particular, ventricular tachycardia. But the authors suggest that the enlarged myocytes may themselves be predisposing to arrhythmias, rather than fibrosis,” Dr. Fitzgibbons said.

The study was supported by Cardiac Risk in the Young. Dr. Westaby and Dr. Fitzgibbons have reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Obesity, in and of itself, and independent of other cardiovascular risk factors, may cause changes to the heart that can lead to sudden cardiac death, a new case-control study suggests.

Researchers who analyzed hearts taken at autopsy from people who had died from sudden cardiac death found that a number of the hearts obtained from obese decedents were heavier than those from normal-weight decedents and that the hazard ratio of unexplained cardiomegaly in this cohort was 5.3, compared with normal-weight individuals.

“Even when we ruled out any conditions that could potentially cause enlargement of the heart, including hypertension, heart valve problems, diabetes, and other cardiovascular risk factors, the association with obesity cardiomyopathy, or OCM, and sudden cardiac death remained,” lead author Joseph Westaby, PhD, from the Cardiac Risk in the Young (CRY) Cardiovascular Pathology Laboratories at St George’s University of London, said in an interview.

The study was published online in JACC: Advances.

Intrigued by this finding, Dr. Westaby and associates sought to characterize the clinical and pathological features of OCM associated with sudden cardiac death by comparing this population to two control groups: sudden cardiac death patients who were either obese or of normal weight, and had morphologically normal hearts.

Their group is uniquely positioned to do such research, Dr. Westaby explained.

“Here at St George’s University of London, we have a specialized cardiovascular pathology service. ... All hearts obtained at autopsy from individuals who have died from sudden cardiac death, or who were suspected to have had a cardiovascular cause of death, anywhere in the U.K., are referred to the CRY Centre for further analysis,” he said.

Patients were divided into two groups according to body mass index: an obesity group (BMI > 30 kg/m²) and a normal-weight group (BMI, 18.5-24.9).

An increased heart weight above 550 g in men and 450 g in women in the absence of coronary artery disease, hypertension, diabetes, or valvular disease was classified as unexplained cardiomegaly, and individuals with obesity and cardiomegaly were defined as obesity cardiomyopathy.

Age- and sex-matched controls with obesity (n = 106) were selected based on a BMI greater than 30, with a morphologically normal heart weighing less than 550 g in men and than 450 g in women. 

Age- and sex-matched normal weight controls (n = 106) were selected based on a BMI of 18.5-24.9 and a morphologically normal heart weighing less than 550 g in men and less than 450 g in women. 

The researchers identified 53 OCM cases from a cohort of more than 4,500 sudden cardiac death cases that had BMI measurements. In normal-weight patients, there were 14 cases of unexplained cardiomegaly.

The mean age at death of individuals with OCM was 42 years (range, 30-54 years). Most of the deaths occurred in men (n = 34; 64%), who also died younger than women (40 ± 13 years vs. 45 ± 10 years; P = .036).

The average heart weight in OCM patients was 598 ± 93 g. Risk of sudden cardiac death increased when BMI reached 35.

Compared with matched controls, there were increases in right and left ventricular wall thickness (all P < .05) in OCM cases. Right ventricular epicardial fat was increased in OCM cases, compared with normal-weight controls only.

Left ventricular fibrosis was identified in seven (13%) OCM cases.
 

Role of genetics to be explored

“This study highlights the need for further investigation into these individuals because, at the moment, we can’t be sure that the only contributing factor to this is the obesity,” said Dr. Westaby.

In the works are plans to see if there may be an underlying genetic predisposition in obese individuals that may have contributed to the development of an enlarged heart. The group also plans to study the families of the deceased individuals to determine if they are at risk of developing cardiomegaly, he said.

“This paper makes an important contribution to the literature that raises many important questions for future research,” Timothy P. Fitzgibbons, MD, PhD, from the University of Massachusetts, Worcester, wrote in an accompanying editorial.

Being able to access so many autopsy samples gives the current study considerable heft, Dr. Fitzgibbons said in an interview.

“A lot has been made of the obesity paradox and the perhaps benign nature of obesity but this paper suggests the opposite, that it is a very serious problem and can, in fact, in and of itself, cause heart abnormalities that could cause sudden death,” he noted.

The fact that only 13% of OCM cases had fibrosis on histology suggests that fibrosis was not the main cause of sudden cardiac death, he said.

“Often we will do MRIs to look for areas of fibrosis within the heart because those areas make patients prone to re-entry arrhythmias, in particular, ventricular tachycardia. But the authors suggest that the enlarged myocytes may themselves be predisposing to arrhythmias, rather than fibrosis,” Dr. Fitzgibbons said.

The study was supported by Cardiac Risk in the Young. Dr. Westaby and Dr. Fitzgibbons have reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Obesity, in and of itself, and independent of other cardiovascular risk factors, may cause changes to the heart that can lead to sudden cardiac death, a new case-control study suggests.

Researchers who analyzed hearts taken at autopsy from people who had died from sudden cardiac death found that a number of the hearts obtained from obese decedents were heavier than those from normal-weight decedents and that the hazard ratio of unexplained cardiomegaly in this cohort was 5.3, compared with normal-weight individuals.

“Even when we ruled out any conditions that could potentially cause enlargement of the heart, including hypertension, heart valve problems, diabetes, and other cardiovascular risk factors, the association with obesity cardiomyopathy, or OCM, and sudden cardiac death remained,” lead author Joseph Westaby, PhD, from the Cardiac Risk in the Young (CRY) Cardiovascular Pathology Laboratories at St George’s University of London, said in an interview.

The study was published online in JACC: Advances.

Intrigued by this finding, Dr. Westaby and associates sought to characterize the clinical and pathological features of OCM associated with sudden cardiac death by comparing this population to two control groups: sudden cardiac death patients who were either obese or of normal weight, and had morphologically normal hearts.

Their group is uniquely positioned to do such research, Dr. Westaby explained.

“Here at St George’s University of London, we have a specialized cardiovascular pathology service. ... All hearts obtained at autopsy from individuals who have died from sudden cardiac death, or who were suspected to have had a cardiovascular cause of death, anywhere in the U.K., are referred to the CRY Centre for further analysis,” he said.

Patients were divided into two groups according to body mass index: an obesity group (BMI > 30 kg/m²) and a normal-weight group (BMI, 18.5-24.9).

An increased heart weight above 550 g in men and 450 g in women in the absence of coronary artery disease, hypertension, diabetes, or valvular disease was classified as unexplained cardiomegaly, and individuals with obesity and cardiomegaly were defined as obesity cardiomyopathy.

Age- and sex-matched controls with obesity (n = 106) were selected based on a BMI greater than 30, with a morphologically normal heart weighing less than 550 g in men and than 450 g in women. 

Age- and sex-matched normal weight controls (n = 106) were selected based on a BMI of 18.5-24.9 and a morphologically normal heart weighing less than 550 g in men and less than 450 g in women. 

The researchers identified 53 OCM cases from a cohort of more than 4,500 sudden cardiac death cases that had BMI measurements. In normal-weight patients, there were 14 cases of unexplained cardiomegaly.

The mean age at death of individuals with OCM was 42 years (range, 30-54 years). Most of the deaths occurred in men (n = 34; 64%), who also died younger than women (40 ± 13 years vs. 45 ± 10 years; P = .036).

The average heart weight in OCM patients was 598 ± 93 g. Risk of sudden cardiac death increased when BMI reached 35.

Compared with matched controls, there were increases in right and left ventricular wall thickness (all P < .05) in OCM cases. Right ventricular epicardial fat was increased in OCM cases, compared with normal-weight controls only.

Left ventricular fibrosis was identified in seven (13%) OCM cases.
 

Role of genetics to be explored

“This study highlights the need for further investigation into these individuals because, at the moment, we can’t be sure that the only contributing factor to this is the obesity,” said Dr. Westaby.

In the works are plans to see if there may be an underlying genetic predisposition in obese individuals that may have contributed to the development of an enlarged heart. The group also plans to study the families of the deceased individuals to determine if they are at risk of developing cardiomegaly, he said.

“This paper makes an important contribution to the literature that raises many important questions for future research,” Timothy P. Fitzgibbons, MD, PhD, from the University of Massachusetts, Worcester, wrote in an accompanying editorial.

Being able to access so many autopsy samples gives the current study considerable heft, Dr. Fitzgibbons said in an interview.

“A lot has been made of the obesity paradox and the perhaps benign nature of obesity but this paper suggests the opposite, that it is a very serious problem and can, in fact, in and of itself, cause heart abnormalities that could cause sudden death,” he noted.

The fact that only 13% of OCM cases had fibrosis on histology suggests that fibrosis was not the main cause of sudden cardiac death, he said.

“Often we will do MRIs to look for areas of fibrosis within the heart because those areas make patients prone to re-entry arrhythmias, in particular, ventricular tachycardia. But the authors suggest that the enlarged myocytes may themselves be predisposing to arrhythmias, rather than fibrosis,” Dr. Fitzgibbons said.

The study was supported by Cardiac Risk in the Young. Dr. Westaby and Dr. Fitzgibbons have reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Left atrial appendage occlusion (LAAO) is associated with fewer injuries and less bleeding from falls than anticoagulant medications in patients with atrial fibrillation (AF) and a previous stroke, a new cohort study suggests.

Investigators prospectively followed more than 1,250 patients with AF and a previous ischemic stroke. Approximately half underwent LAAO, while the other half were treated with direct oral anticoagulants (DOACs). Patients were followed for close to 2 years.

Slightly more than 20% of patients fell during that period in each group, and after their falls, patients on DOACs had significantly more severe injuries and longer hospital stays, compared with those treated by LAAO, who were not taking anticoagulants. The risk for a major bleed, including an intracranial bleed, was 70% lower in the LAAO group.

LAAO has previously been considered for people at risk of bleeding events – for example, those with gastrointestinal (GI) bleeds, bruising, or intracranial bleeding – but had not yet been studied in those at risk for falls, coauthor Moussa Mansour, MD, professor of medicine, Harvard Medical School, and director of the Atrial Fibrillation Program at Massachusetts General Hospital, Boston, said in an interview.

This is the first study to focus on LAAO specifically for those at risk for falling and demonstrated that the LAAO has utility in this population as well, which is important because the U.S. population is an aging population, and at advanced ages, “people’s balance becomes unsteady and they are at high risk of falling,” he said.

The findings were published online as a research letter in the Journal of the American College of Cardiology.
 

Multidisciplinary collaboration

“More than one in five of our neurology patients with AF fall – many with devastating consequences – making stroke prevention extremely challenging,” senior author MingMing Ning, MD, MMsc, associate professor of neurology, Harvard Medical School, and director of the Cardio-Neurology and the Clinical Proteomics Research Center at Massachusetts General Hospital, Boston, said in an interview.

“There is a dire need to tailor treatment to keep our patients safe while preventing future strokes,” she said.

Anticoagulants are effective in stroke prevention in these patients but are associated with a higher risk for major bleeding, especially after a fall.

The current prospective observational study recruited 1,266 stroke patients who were treated either with LAAO or DOACs (n = 570 and 696, respectively). Patients were followed for a median of 1.8 years (IQR: 0.9-3.0).

During the follow-up period, 22.6% of LAAO-treated patients and 22.7% of DOAC-treated patients sustained a fall (mean age 78.9 years, 57.4% male and 79.1 years, 52.5% male respectively).

Fall severity, evaluated via the Injury Severity Score, was less in the LAAO vs. the DOAC group, with ISS scores of 1 (IQR 1-4) vs. 4 (IQR 1.75-9).

LAAO was associated with significantly reduced severity of fall-related injuries (OR, –1.09, 95% confidence interval [CI], –1.52 to –0.66; P < .001) – a finding that remained statistically significant after adjustment for confounders such as age, sex, and comorbidities contributing to fall risk, such as hypertension, hyperlipidemia, and diabetes.

The incidence of major trauma (defined as ISS >15) was lower in the LAAO group, compared to the DOAC group (0.8% vs. 6.3%, respectively, P = .026), and LAAO-treated patients had a shorter length of hospital stay, with fewer LAAO patients compared with DOAC patients staying in the hospital for more than 3 days (17% vs. 29.1%, respectively, P = .018).

The risk for major post-fall bleeding was lower in the LAAO vs. the DOAC group (4.7% vs. 15.2%, AOR, 0.29; 95% CI, 0.11-0.73; P = .009) – a finding that included intracranial bleeding (3.1% vs. 9.5%; AOR, 0.29; 95% CI, 0.09-0.90; P = .033).

“Many people are living to advanced ages, where their balance becomes unsteady, and in addition, we have an increase in the prevalence of AF because people are living longer and it’s a disease of the elderly, because we have more hypertension, and we also have more tools to diagnose AF. It’s almost a ‘perfect storm’ situation, and we need effective interventions in this population,” said Dr. Mansour.

Before the study, people at risk for falling were not being considered for LAAO; but now, “we believe they should be considered,” he added. “And although people in the current study had all experienced an ischemic stroke, any patient at risk of a fall will potentially benefit.”

Beyond demonstrating the role of LAAO in reducing the risk of post-fall bleeding injuries, the study – which was conducted by specialists in neurology and cardiology among other fields – highlights the importance of multidisciplinary collaboration, which is “key” for effective stroke prevention, Dr. Ning said.

She emphasized that “we need to learn from our patients and tailor treatment to their needs. A patient’s risk of falling, lifestyle, and medication adherence are all important for individualizing care and improving quality of life.”
 

Better option

Commenting for this article, Andrea Natale, MD, executive medical director, Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, said the authors “should be commended for this prospective study on real-world patients that has yielded highly meaningful data from a clinical standpoint.”

Dr. Natale, who was not involved with the study, said it has “several strong points,” such as a fairly large sample size, exclusive population with a history of AF-related stroke, long follow-up duration, evaluation of fall incidents by blinded experts, and severity of fall assessed by a validated questionnaire.

“This is the first study that directly compared the outcomes of traumatic fall in patients receiving LAAO vs. DOAC,” he said. “Given that history of fall is an independent predictor of bleeding and death, the study findings by Deng et al. offer the hope for a safer life with the LAAO option in the aging, fall-prone AF population.”

The take-home message is that, in patients with history of stroke, LAAO “is a better option, in terms of significantly reduced injury severity and shortened hospital length of stay after traumatic falls,” Dr. Natale said.

This study was supported in part by research grants from Boston Scientific, the Leducq Foundation, and the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Natale is a consultant for Abbott, Baylis, Biosense Webster, Biotronik, Boston Scientific, and Medtronic.
 

A version of this article appeared on Medscape.com.

Left atrial appendage occlusion (LAAO) is associated with fewer injuries and less bleeding from falls than anticoagulant medications in patients with atrial fibrillation (AF) and a previous stroke, a new cohort study suggests.

Investigators prospectively followed more than 1,250 patients with AF and a previous ischemic stroke. Approximately half underwent LAAO, while the other half were treated with direct oral anticoagulants (DOACs). Patients were followed for close to 2 years.

Slightly more than 20% of patients fell during that period in each group, and after their falls, patients on DOACs had significantly more severe injuries and longer hospital stays, compared with those treated by LAAO, who were not taking anticoagulants. The risk for a major bleed, including an intracranial bleed, was 70% lower in the LAAO group.

LAAO has previously been considered for people at risk of bleeding events – for example, those with gastrointestinal (GI) bleeds, bruising, or intracranial bleeding – but had not yet been studied in those at risk for falls, coauthor Moussa Mansour, MD, professor of medicine, Harvard Medical School, and director of the Atrial Fibrillation Program at Massachusetts General Hospital, Boston, said in an interview.

This is the first study to focus on LAAO specifically for those at risk for falling and demonstrated that the LAAO has utility in this population as well, which is important because the U.S. population is an aging population, and at advanced ages, “people’s balance becomes unsteady and they are at high risk of falling,” he said.

The findings were published online as a research letter in the Journal of the American College of Cardiology.
 

Multidisciplinary collaboration

“More than one in five of our neurology patients with AF fall – many with devastating consequences – making stroke prevention extremely challenging,” senior author MingMing Ning, MD, MMsc, associate professor of neurology, Harvard Medical School, and director of the Cardio-Neurology and the Clinical Proteomics Research Center at Massachusetts General Hospital, Boston, said in an interview.

“There is a dire need to tailor treatment to keep our patients safe while preventing future strokes,” she said.

Anticoagulants are effective in stroke prevention in these patients but are associated with a higher risk for major bleeding, especially after a fall.

The current prospective observational study recruited 1,266 stroke patients who were treated either with LAAO or DOACs (n = 570 and 696, respectively). Patients were followed for a median of 1.8 years (IQR: 0.9-3.0).

During the follow-up period, 22.6% of LAAO-treated patients and 22.7% of DOAC-treated patients sustained a fall (mean age 78.9 years, 57.4% male and 79.1 years, 52.5% male respectively).

Fall severity, evaluated via the Injury Severity Score, was less in the LAAO vs. the DOAC group, with ISS scores of 1 (IQR 1-4) vs. 4 (IQR 1.75-9).

LAAO was associated with significantly reduced severity of fall-related injuries (OR, –1.09, 95% confidence interval [CI], –1.52 to –0.66; P < .001) – a finding that remained statistically significant after adjustment for confounders such as age, sex, and comorbidities contributing to fall risk, such as hypertension, hyperlipidemia, and diabetes.

The incidence of major trauma (defined as ISS >15) was lower in the LAAO group, compared to the DOAC group (0.8% vs. 6.3%, respectively, P = .026), and LAAO-treated patients had a shorter length of hospital stay, with fewer LAAO patients compared with DOAC patients staying in the hospital for more than 3 days (17% vs. 29.1%, respectively, P = .018).

The risk for major post-fall bleeding was lower in the LAAO vs. the DOAC group (4.7% vs. 15.2%, AOR, 0.29; 95% CI, 0.11-0.73; P = .009) – a finding that included intracranial bleeding (3.1% vs. 9.5%; AOR, 0.29; 95% CI, 0.09-0.90; P = .033).

“Many people are living to advanced ages, where their balance becomes unsteady, and in addition, we have an increase in the prevalence of AF because people are living longer and it’s a disease of the elderly, because we have more hypertension, and we also have more tools to diagnose AF. It’s almost a ‘perfect storm’ situation, and we need effective interventions in this population,” said Dr. Mansour.

Before the study, people at risk for falling were not being considered for LAAO; but now, “we believe they should be considered,” he added. “And although people in the current study had all experienced an ischemic stroke, any patient at risk of a fall will potentially benefit.”

Beyond demonstrating the role of LAAO in reducing the risk of post-fall bleeding injuries, the study – which was conducted by specialists in neurology and cardiology among other fields – highlights the importance of multidisciplinary collaboration, which is “key” for effective stroke prevention, Dr. Ning said.

She emphasized that “we need to learn from our patients and tailor treatment to their needs. A patient’s risk of falling, lifestyle, and medication adherence are all important for individualizing care and improving quality of life.”
 

Better option

Commenting for this article, Andrea Natale, MD, executive medical director, Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, said the authors “should be commended for this prospective study on real-world patients that has yielded highly meaningful data from a clinical standpoint.”

Dr. Natale, who was not involved with the study, said it has “several strong points,” such as a fairly large sample size, exclusive population with a history of AF-related stroke, long follow-up duration, evaluation of fall incidents by blinded experts, and severity of fall assessed by a validated questionnaire.

“This is the first study that directly compared the outcomes of traumatic fall in patients receiving LAAO vs. DOAC,” he said. “Given that history of fall is an independent predictor of bleeding and death, the study findings by Deng et al. offer the hope for a safer life with the LAAO option in the aging, fall-prone AF population.”

The take-home message is that, in patients with history of stroke, LAAO “is a better option, in terms of significantly reduced injury severity and shortened hospital length of stay after traumatic falls,” Dr. Natale said.

This study was supported in part by research grants from Boston Scientific, the Leducq Foundation, and the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Natale is a consultant for Abbott, Baylis, Biosense Webster, Biotronik, Boston Scientific, and Medtronic.
 

A version of this article appeared on Medscape.com.

Left atrial appendage occlusion (LAAO) is associated with fewer injuries and less bleeding from falls than anticoagulant medications in patients with atrial fibrillation (AF) and a previous stroke, a new cohort study suggests.

Investigators prospectively followed more than 1,250 patients with AF and a previous ischemic stroke. Approximately half underwent LAAO, while the other half were treated with direct oral anticoagulants (DOACs). Patients were followed for close to 2 years.

Slightly more than 20% of patients fell during that period in each group, and after their falls, patients on DOACs had significantly more severe injuries and longer hospital stays, compared with those treated by LAAO, who were not taking anticoagulants. The risk for a major bleed, including an intracranial bleed, was 70% lower in the LAAO group.

LAAO has previously been considered for people at risk of bleeding events – for example, those with gastrointestinal (GI) bleeds, bruising, or intracranial bleeding – but had not yet been studied in those at risk for falls, coauthor Moussa Mansour, MD, professor of medicine, Harvard Medical School, and director of the Atrial Fibrillation Program at Massachusetts General Hospital, Boston, said in an interview.

This is the first study to focus on LAAO specifically for those at risk for falling and demonstrated that the LAAO has utility in this population as well, which is important because the U.S. population is an aging population, and at advanced ages, “people’s balance becomes unsteady and they are at high risk of falling,” he said.

The findings were published online as a research letter in the Journal of the American College of Cardiology.
 

Multidisciplinary collaboration

“More than one in five of our neurology patients with AF fall – many with devastating consequences – making stroke prevention extremely challenging,” senior author MingMing Ning, MD, MMsc, associate professor of neurology, Harvard Medical School, and director of the Cardio-Neurology and the Clinical Proteomics Research Center at Massachusetts General Hospital, Boston, said in an interview.

“There is a dire need to tailor treatment to keep our patients safe while preventing future strokes,” she said.

Anticoagulants are effective in stroke prevention in these patients but are associated with a higher risk for major bleeding, especially after a fall.

The current prospective observational study recruited 1,266 stroke patients who were treated either with LAAO or DOACs (n = 570 and 696, respectively). Patients were followed for a median of 1.8 years (IQR: 0.9-3.0).

During the follow-up period, 22.6% of LAAO-treated patients and 22.7% of DOAC-treated patients sustained a fall (mean age 78.9 years, 57.4% male and 79.1 years, 52.5% male respectively).

Fall severity, evaluated via the Injury Severity Score, was less in the LAAO vs. the DOAC group, with ISS scores of 1 (IQR 1-4) vs. 4 (IQR 1.75-9).

LAAO was associated with significantly reduced severity of fall-related injuries (OR, –1.09, 95% confidence interval [CI], –1.52 to –0.66; P < .001) – a finding that remained statistically significant after adjustment for confounders such as age, sex, and comorbidities contributing to fall risk, such as hypertension, hyperlipidemia, and diabetes.

The incidence of major trauma (defined as ISS >15) was lower in the LAAO group, compared to the DOAC group (0.8% vs. 6.3%, respectively, P = .026), and LAAO-treated patients had a shorter length of hospital stay, with fewer LAAO patients compared with DOAC patients staying in the hospital for more than 3 days (17% vs. 29.1%, respectively, P = .018).

The risk for major post-fall bleeding was lower in the LAAO vs. the DOAC group (4.7% vs. 15.2%, AOR, 0.29; 95% CI, 0.11-0.73; P = .009) – a finding that included intracranial bleeding (3.1% vs. 9.5%; AOR, 0.29; 95% CI, 0.09-0.90; P = .033).

“Many people are living to advanced ages, where their balance becomes unsteady, and in addition, we have an increase in the prevalence of AF because people are living longer and it’s a disease of the elderly, because we have more hypertension, and we also have more tools to diagnose AF. It’s almost a ‘perfect storm’ situation, and we need effective interventions in this population,” said Dr. Mansour.

Before the study, people at risk for falling were not being considered for LAAO; but now, “we believe they should be considered,” he added. “And although people in the current study had all experienced an ischemic stroke, any patient at risk of a fall will potentially benefit.”

Beyond demonstrating the role of LAAO in reducing the risk of post-fall bleeding injuries, the study – which was conducted by specialists in neurology and cardiology among other fields – highlights the importance of multidisciplinary collaboration, which is “key” for effective stroke prevention, Dr. Ning said.

She emphasized that “we need to learn from our patients and tailor treatment to their needs. A patient’s risk of falling, lifestyle, and medication adherence are all important for individualizing care and improving quality of life.”
 

Better option

Commenting for this article, Andrea Natale, MD, executive medical director, Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, said the authors “should be commended for this prospective study on real-world patients that has yielded highly meaningful data from a clinical standpoint.”

Dr. Natale, who was not involved with the study, said it has “several strong points,” such as a fairly large sample size, exclusive population with a history of AF-related stroke, long follow-up duration, evaluation of fall incidents by blinded experts, and severity of fall assessed by a validated questionnaire.

“This is the first study that directly compared the outcomes of traumatic fall in patients receiving LAAO vs. DOAC,” he said. “Given that history of fall is an independent predictor of bleeding and death, the study findings by Deng et al. offer the hope for a safer life with the LAAO option in the aging, fall-prone AF population.”

The take-home message is that, in patients with history of stroke, LAAO “is a better option, in terms of significantly reduced injury severity and shortened hospital length of stay after traumatic falls,” Dr. Natale said.

This study was supported in part by research grants from Boston Scientific, the Leducq Foundation, and the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Natale is a consultant for Abbott, Baylis, Biosense Webster, Biotronik, Boston Scientific, and Medtronic.
 

A version of this article appeared on Medscape.com.

SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.

Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that use of injectable agonists of glucagonlike peptide-1 (GLP1) appears to hasten the progression of diabetic retinopathy and diabetic macular edema (DME).

Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.

Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.

GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.

Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
 

Albiglutide the key culprit?

In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).

Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.

“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
 

What causes progression?

Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.

“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”

The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.

Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that use of injectable agonists of glucagonlike peptide-1 (GLP1) appears to hasten the progression of diabetic retinopathy and diabetic macular edema (DME).

Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.

Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.

GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.

Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
 

Albiglutide the key culprit?

In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).

Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.

“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
 

What causes progression?

Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.

“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”

The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.

Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that use of injectable agonists of glucagonlike peptide-1 (GLP1) appears to hasten the progression of diabetic retinopathy and diabetic macular edema (DME).

Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.

Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.

GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.

Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
 

Albiglutide the key culprit?

In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).

Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.

“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
 

What causes progression?

Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.

“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”

The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

Some clinicians say it’s “confusing” and “ridiculous” to change the name and diagnostic criteria of an established liver disease, while others bemoan the seemingly political reasons why it happened. Yet recently, 236 panelists from 56 countries decided that the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) rely on “exclusionary confounder terms and the use of potentially stigmatizing language.”

In a report published in Hepatology, the panelists, members of the NAFLD Nomenclature Consensus Group, determined that steatotic liver disease (SLD) would be used as an “overarching term to encompass the various etiologies of steatosis.”

Metabolic dysfunction–associated steatotic liver disease (MASLD) was chosen to replace NAFLD, and the definition was changed to include at least one of five cardiometabolic risk factors.

Metabolic dysfunction–associated steatohepatitis (MASH) replaces NASH. 

Those with no metabolic parameters and no known cause will be diagnosed with cryptogenic SLD.

A new category, MetALD, now describes those with MASLD who drink more alcohol per week – 140-350 g for men and 210-420 g for women.

The changes did not sit well with this news organization’s readers from diverse specialties, including family practice, critical care, and gastroenterology.

In its report, the consensus group wrote that 74% of respondents to its rounds of surveys felt the current nomenclature “was sufficiently flawed to consider a name change.”

The terms “nonalcoholic” and “fatty” were felt to be stigmatizing by 61% and 66% of respondents, respectively, according to the group, a multi-stakeholder effort under the auspices of the American Association for Study of Liver Disease and the European Association for Study of the Liver, in collaboration with the Asociación Latinoamericana para el Estudio del Hígado.

Consensus was defined a priori as a supermajority (67%) vote. 

“The new nomenclature and diagnostic criteria are widely supported, nonstigmatizing, and can improve awareness and patient identification,” the group concluded.

“No way” sums up many of the almost 60 reader comments received on this news organization’s story covering the change. Readers must share medical credentials to publicly comment on stories.
 

‘Confusing’ and ‘ridiculous’

A number of readers questioned how the changes will help practice.

“Once again, the specialists and other experts are changing the nomenclature to make the subject even more confusing for us primary care practitioners,” an HIV/AIDS physician wrote. “They obviously have no idea what [primary care practitioners] have to put up with day in and day out. All such revisions do is increase the cynicism and anger so many [primary care practitioners] have.”

Similarly, an internist said, “These new terms are going to confuse both doctors and patients. When you give a patient a diagnosis like this, they will not understand it, and will not be able to act as they should to correct it.”

“ ‘Fatty liver’ is a jargon-free diagnosis, easy to understand and easy for patients to know what they need to do,” the internist continued. “You think patients are gonna be educated when you tell them they have a ‘metabolic disease’? 100% they will not know what you’re talking about.”

Yet another wondered, “If SLD is the ‘umbrella’ term, why (are) MetALD and ALD not MetASLD and ASLD, respectively? Furthermore, efforts to ‘destigmatize’ terminology will inadvertently condemn cryptogenic SLD (CSLD) as the new ‘closet alcoholic.’ “

“Perhaps a subclassification, CSLD-HDIRDD (CSLD–Honest, Doc, I Really Don’t Drink),” the reader added.

“Everything about this is ridiculous,” a family physician wrote. “How long will it be until the experts change obesity to ‘gravitationally challenged’ as a diagnosis!”

“I was thinking of ‘circumferentially challenged,’” a reader in Canada chimed in. “But that would be ‘body shaming’ would it not?”

This reader continued, asking, “What about returning to the old practice of using Latin names patients don’t understand so there is no ‘shame’ attached to them? Or what about this revolutionary idea: To just say it as it is – fat?”
 

Acceding to ‘wokeness’

A sizable number of readers felt the name changes were motivated by a “woke” awareness.

“The effect of this new ‘woke’ clarity is ridiculous and simply not worth it! Can we justify the cost of this? Patients will have to learn all over again how to discuss their condition,” said one reader.

The reader continued, saying, “The Internet and social media freely use the term ‘fat’ – and despite not wanting to offend – there seems to be universal agreement that FAT, in certain conditions or places, is unhealthy and undesirable.

“Why is the medical community so afraid to tell it like it is? I might hurt your feelings, but I could save your life,” concluded the reader.
 

Defending change

One commentator, a hepatologist in France, defended the changes and responded to some of complaints.

“Maybe people who comment here should read the article, reflect, and understand the reasons why the old nomenclature and definition were scientifically inaccurate and needed to be changed,” the commentator wrote.

“It was an exclusionary, negative definition not recognizing the root of the disease (adipose tissue dysfunction with insulin resistance – instead defining it by what it is not ...) and not allowing the recognition of a large segment of the population [that] accumulates metabolic risk factors and moderate alcohol consumption. These patients were left out of all studies. Those were the main reasons for change and not the stigma part – with the word ‘fatty’ only being an issue in English-speaking countries, not elsewhere,” the commentator continued.

“Calls for change have been voiced for 20 years and a first comprehensive attempt (called MAFLD) was introduced 3 years ago (J Hepatol. 2020;73:202-9). Please, a little bit of respect and restraint in the comments recognizing the research efforts and publications for those that contributed to the field over the past 25 years ...” the hepatologist wrote.

The reader added, “Clinicians and researchers were dissatisfied for a long time, but it took years to gather overwhelming evidence demonstrating what causes the disease and then to kickstart a process under the auspices of several multinational scientific societies and come up with something consensually agreed upon by a large number of clinician researchers.

“Now you can tell your patient that he has metabolic liver disease instead of telling him that the problem at the root of his disease is that he is not drinking alcohol (nonalcoholic steatohepatitis). So, again, it is not so much about changing a name but about redefining diagnostic criteria and a nosological framework,” the reader wrote.

Other readers responded to the defender:

“This nomenclature issue has been churned for 20+ years? Well, the mountain has labored heavily, and given birth to a mouse,” one said.

“Still, how is this going to help in the clinical management? The whole gamut of conditions are evaluated and treated as a whole, not in isolation,” a general practitioner in India said. “If someone has a risk factor or not, continuous follow-up is required as a whole, whether it’s nonalcoholic or alcoholic, or whatever term is coined up.”

Finally, a family physician said, “It just rolls off the tongue, doesn’t it? But I have to admit, it’s the one place where ‘persons’ from 56 countries can get together and agree on something. Not even politicians can do that! Me, I’m sticking with NAFLD.”

A version of this article first appeared on Medscape.com.

Some clinicians say it’s “confusing” and “ridiculous” to change the name and diagnostic criteria of an established liver disease, while others bemoan the seemingly political reasons why it happened. Yet recently, 236 panelists from 56 countries decided that the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) rely on “exclusionary confounder terms and the use of potentially stigmatizing language.”

In a report published in Hepatology, the panelists, members of the NAFLD Nomenclature Consensus Group, determined that steatotic liver disease (SLD) would be used as an “overarching term to encompass the various etiologies of steatosis.”

Metabolic dysfunction–associated steatotic liver disease (MASLD) was chosen to replace NAFLD, and the definition was changed to include at least one of five cardiometabolic risk factors.

Metabolic dysfunction–associated steatohepatitis (MASH) replaces NASH. 

Those with no metabolic parameters and no known cause will be diagnosed with cryptogenic SLD.

A new category, MetALD, now describes those with MASLD who drink more alcohol per week – 140-350 g for men and 210-420 g for women.

The changes did not sit well with this news organization’s readers from diverse specialties, including family practice, critical care, and gastroenterology.

In its report, the consensus group wrote that 74% of respondents to its rounds of surveys felt the current nomenclature “was sufficiently flawed to consider a name change.”

The terms “nonalcoholic” and “fatty” were felt to be stigmatizing by 61% and 66% of respondents, respectively, according to the group, a multi-stakeholder effort under the auspices of the American Association for Study of Liver Disease and the European Association for Study of the Liver, in collaboration with the Asociación Latinoamericana para el Estudio del Hígado.

Consensus was defined a priori as a supermajority (67%) vote. 

“The new nomenclature and diagnostic criteria are widely supported, nonstigmatizing, and can improve awareness and patient identification,” the group concluded.

“No way” sums up many of the almost 60 reader comments received on this news organization’s story covering the change. Readers must share medical credentials to publicly comment on stories.
 

‘Confusing’ and ‘ridiculous’

A number of readers questioned how the changes will help practice.

“Once again, the specialists and other experts are changing the nomenclature to make the subject even more confusing for us primary care practitioners,” an HIV/AIDS physician wrote. “They obviously have no idea what [primary care practitioners] have to put up with day in and day out. All such revisions do is increase the cynicism and anger so many [primary care practitioners] have.”

Similarly, an internist said, “These new terms are going to confuse both doctors and patients. When you give a patient a diagnosis like this, they will not understand it, and will not be able to act as they should to correct it.”

“ ‘Fatty liver’ is a jargon-free diagnosis, easy to understand and easy for patients to know what they need to do,” the internist continued. “You think patients are gonna be educated when you tell them they have a ‘metabolic disease’? 100% they will not know what you’re talking about.”

Yet another wondered, “If SLD is the ‘umbrella’ term, why (are) MetALD and ALD not MetASLD and ASLD, respectively? Furthermore, efforts to ‘destigmatize’ terminology will inadvertently condemn cryptogenic SLD (CSLD) as the new ‘closet alcoholic.’ “

“Perhaps a subclassification, CSLD-HDIRDD (CSLD–Honest, Doc, I Really Don’t Drink),” the reader added.

“Everything about this is ridiculous,” a family physician wrote. “How long will it be until the experts change obesity to ‘gravitationally challenged’ as a diagnosis!”

“I was thinking of ‘circumferentially challenged,’” a reader in Canada chimed in. “But that would be ‘body shaming’ would it not?”

This reader continued, asking, “What about returning to the old practice of using Latin names patients don’t understand so there is no ‘shame’ attached to them? Or what about this revolutionary idea: To just say it as it is – fat?”
 

Acceding to ‘wokeness’

A sizable number of readers felt the name changes were motivated by a “woke” awareness.

“The effect of this new ‘woke’ clarity is ridiculous and simply not worth it! Can we justify the cost of this? Patients will have to learn all over again how to discuss their condition,” said one reader.

The reader continued, saying, “The Internet and social media freely use the term ‘fat’ – and despite not wanting to offend – there seems to be universal agreement that FAT, in certain conditions or places, is unhealthy and undesirable.

“Why is the medical community so afraid to tell it like it is? I might hurt your feelings, but I could save your life,” concluded the reader.
 

Defending change

One commentator, a hepatologist in France, defended the changes and responded to some of complaints.

“Maybe people who comment here should read the article, reflect, and understand the reasons why the old nomenclature and definition were scientifically inaccurate and needed to be changed,” the commentator wrote.

“It was an exclusionary, negative definition not recognizing the root of the disease (adipose tissue dysfunction with insulin resistance – instead defining it by what it is not ...) and not allowing the recognition of a large segment of the population [that] accumulates metabolic risk factors and moderate alcohol consumption. These patients were left out of all studies. Those were the main reasons for change and not the stigma part – with the word ‘fatty’ only being an issue in English-speaking countries, not elsewhere,” the commentator continued.

“Calls for change have been voiced for 20 years and a first comprehensive attempt (called MAFLD) was introduced 3 years ago (J Hepatol. 2020;73:202-9). Please, a little bit of respect and restraint in the comments recognizing the research efforts and publications for those that contributed to the field over the past 25 years ...” the hepatologist wrote.

The reader added, “Clinicians and researchers were dissatisfied for a long time, but it took years to gather overwhelming evidence demonstrating what causes the disease and then to kickstart a process under the auspices of several multinational scientific societies and come up with something consensually agreed upon by a large number of clinician researchers.

“Now you can tell your patient that he has metabolic liver disease instead of telling him that the problem at the root of his disease is that he is not drinking alcohol (nonalcoholic steatohepatitis). So, again, it is not so much about changing a name but about redefining diagnostic criteria and a nosological framework,” the reader wrote.

Other readers responded to the defender:

“This nomenclature issue has been churned for 20+ years? Well, the mountain has labored heavily, and given birth to a mouse,” one said.

“Still, how is this going to help in the clinical management? The whole gamut of conditions are evaluated and treated as a whole, not in isolation,” a general practitioner in India said. “If someone has a risk factor or not, continuous follow-up is required as a whole, whether it’s nonalcoholic or alcoholic, or whatever term is coined up.”

Finally, a family physician said, “It just rolls off the tongue, doesn’t it? But I have to admit, it’s the one place where ‘persons’ from 56 countries can get together and agree on something. Not even politicians can do that! Me, I’m sticking with NAFLD.”

A version of this article first appeared on Medscape.com.

Some clinicians say it’s “confusing” and “ridiculous” to change the name and diagnostic criteria of an established liver disease, while others bemoan the seemingly political reasons why it happened. Yet recently, 236 panelists from 56 countries decided that the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) rely on “exclusionary confounder terms and the use of potentially stigmatizing language.”

In a report published in Hepatology, the panelists, members of the NAFLD Nomenclature Consensus Group, determined that steatotic liver disease (SLD) would be used as an “overarching term to encompass the various etiologies of steatosis.”

Metabolic dysfunction–associated steatotic liver disease (MASLD) was chosen to replace NAFLD, and the definition was changed to include at least one of five cardiometabolic risk factors.

Metabolic dysfunction–associated steatohepatitis (MASH) replaces NASH. 

Those with no metabolic parameters and no known cause will be diagnosed with cryptogenic SLD.

A new category, MetALD, now describes those with MASLD who drink more alcohol per week – 140-350 g for men and 210-420 g for women.

The changes did not sit well with this news organization’s readers from diverse specialties, including family practice, critical care, and gastroenterology.

In its report, the consensus group wrote that 74% of respondents to its rounds of surveys felt the current nomenclature “was sufficiently flawed to consider a name change.”

The terms “nonalcoholic” and “fatty” were felt to be stigmatizing by 61% and 66% of respondents, respectively, according to the group, a multi-stakeholder effort under the auspices of the American Association for Study of Liver Disease and the European Association for Study of the Liver, in collaboration with the Asociación Latinoamericana para el Estudio del Hígado.

Consensus was defined a priori as a supermajority (67%) vote. 

“The new nomenclature and diagnostic criteria are widely supported, nonstigmatizing, and can improve awareness and patient identification,” the group concluded.

“No way” sums up many of the almost 60 reader comments received on this news organization’s story covering the change. Readers must share medical credentials to publicly comment on stories.
 

‘Confusing’ and ‘ridiculous’

A number of readers questioned how the changes will help practice.

“Once again, the specialists and other experts are changing the nomenclature to make the subject even more confusing for us primary care practitioners,” an HIV/AIDS physician wrote. “They obviously have no idea what [primary care practitioners] have to put up with day in and day out. All such revisions do is increase the cynicism and anger so many [primary care practitioners] have.”

Similarly, an internist said, “These new terms are going to confuse both doctors and patients. When you give a patient a diagnosis like this, they will not understand it, and will not be able to act as they should to correct it.”

“ ‘Fatty liver’ is a jargon-free diagnosis, easy to understand and easy for patients to know what they need to do,” the internist continued. “You think patients are gonna be educated when you tell them they have a ‘metabolic disease’? 100% they will not know what you’re talking about.”

Yet another wondered, “If SLD is the ‘umbrella’ term, why (are) MetALD and ALD not MetASLD and ASLD, respectively? Furthermore, efforts to ‘destigmatize’ terminology will inadvertently condemn cryptogenic SLD (CSLD) as the new ‘closet alcoholic.’ “

“Perhaps a subclassification, CSLD-HDIRDD (CSLD–Honest, Doc, I Really Don’t Drink),” the reader added.

“Everything about this is ridiculous,” a family physician wrote. “How long will it be until the experts change obesity to ‘gravitationally challenged’ as a diagnosis!”

“I was thinking of ‘circumferentially challenged,’” a reader in Canada chimed in. “But that would be ‘body shaming’ would it not?”

This reader continued, asking, “What about returning to the old practice of using Latin names patients don’t understand so there is no ‘shame’ attached to them? Or what about this revolutionary idea: To just say it as it is – fat?”
 

Acceding to ‘wokeness’

A sizable number of readers felt the name changes were motivated by a “woke” awareness.

“The effect of this new ‘woke’ clarity is ridiculous and simply not worth it! Can we justify the cost of this? Patients will have to learn all over again how to discuss their condition,” said one reader.

The reader continued, saying, “The Internet and social media freely use the term ‘fat’ – and despite not wanting to offend – there seems to be universal agreement that FAT, in certain conditions or places, is unhealthy and undesirable.

“Why is the medical community so afraid to tell it like it is? I might hurt your feelings, but I could save your life,” concluded the reader.
 

Defending change

One commentator, a hepatologist in France, defended the changes and responded to some of complaints.

“Maybe people who comment here should read the article, reflect, and understand the reasons why the old nomenclature and definition were scientifically inaccurate and needed to be changed,” the commentator wrote.

“It was an exclusionary, negative definition not recognizing the root of the disease (adipose tissue dysfunction with insulin resistance – instead defining it by what it is not ...) and not allowing the recognition of a large segment of the population [that] accumulates metabolic risk factors and moderate alcohol consumption. These patients were left out of all studies. Those were the main reasons for change and not the stigma part – with the word ‘fatty’ only being an issue in English-speaking countries, not elsewhere,” the commentator continued.

“Calls for change have been voiced for 20 years and a first comprehensive attempt (called MAFLD) was introduced 3 years ago (J Hepatol. 2020;73:202-9). Please, a little bit of respect and restraint in the comments recognizing the research efforts and publications for those that contributed to the field over the past 25 years ...” the hepatologist wrote.

The reader added, “Clinicians and researchers were dissatisfied for a long time, but it took years to gather overwhelming evidence demonstrating what causes the disease and then to kickstart a process under the auspices of several multinational scientific societies and come up with something consensually agreed upon by a large number of clinician researchers.

“Now you can tell your patient that he has metabolic liver disease instead of telling him that the problem at the root of his disease is that he is not drinking alcohol (nonalcoholic steatohepatitis). So, again, it is not so much about changing a name but about redefining diagnostic criteria and a nosological framework,” the reader wrote.

Other readers responded to the defender:

“This nomenclature issue has been churned for 20+ years? Well, the mountain has labored heavily, and given birth to a mouse,” one said.

“Still, how is this going to help in the clinical management? The whole gamut of conditions are evaluated and treated as a whole, not in isolation,” a general practitioner in India said. “If someone has a risk factor or not, continuous follow-up is required as a whole, whether it’s nonalcoholic or alcoholic, or whatever term is coined up.”

Finally, a family physician said, “It just rolls off the tongue, doesn’t it? But I have to admit, it’s the one place where ‘persons’ from 56 countries can get together and agree on something. Not even politicians can do that! Me, I’m sticking with NAFLD.”

A version of this article first appeared on Medscape.com.

Time-restricted eating (TRE) can be a practical, easy-to-follow way for some people to control their daily food intake and lose weight. It precludes a person’s need to pay close attention to how much they eat as long as they confine consumption to a limited time window. Plus, results from several recent studies show TRE can further benefit people with type 2 diabetes as well as obesity via mechanisms beyond weight loss.

The most tested and recommended eating window is 8 hours long, although periods up to roughly 10 hours may provide some benefits. Results from multiple studies document that TRE produces modest but consistent weight loss of less than 5% in many people. A recent meta-analysis of 17 randomized controlled studies involving 899 people showed an overall incremental weight loss, compared with controls of 1.60 kg on a TRE regimen.

The more limited data collected so far in people with type 2 diabetes show additional metabolic benefits from TRE, including improved beta-cell responsiveness, increased insulin sensitivity, nonoxidative glucose disposal, increased time in glycemic range, and virtually no hypoglycemic events, Courtney Peterson, PhD, said at the annual scientific sessions of the American Diabetes Association.

‘Eating earlier is better’

An advantage of TRE is that it is “agnostic to food preferences and quality,” said Lisa S. Chow, MD, during a separate session at the meeting. TRE “may have benefits beyond calorie restriction” that appear related to “the timing of eating and the extent of the eating window restriction. Eating earlier [in the day] is better” for markers of metabolic health regardless of how much weight a person may lose on a TRE regimen, noted Dr. Chow, an endocrinologist and professor at the University of Minnesota Medical School, Minneapolis.

But the TRE paradigm seems amenable to some flexibility on the timing for the eating window while still having benefit.

“Self-selected eating windows are usually late,” Dr. Chow observed, and because compliance with a constrained eating window matters, it may be worth allowing people to choose whichever time window for eating works best for them.

“If you let people pick their eating window, they typically include dinner,” said Dr. Chow, who has run a small TRE study that showed this.

“To maximize the effects [of TRE] people should use the eating window that best fits their life,” agreed Kelsey Gabel, PhD, who also gave a TRE talk during the meeting. “Eating most of your [daily] calories first thing in the morning would have the best cardiometabolic benefit, but reduced adherence would mitigate the benefit,” said Dr. Gabel, a nutrition researcher at the University of Illinois.
 

‘Meeting people where they’re at’

“We can have a larger public health impact by meeting people where they’re at. People should position their eating window where it best fits so they can achieve calorie restriction without even knowing it,” Dr. Gabel advised.

She cited a report as evidence that most people prefer a later eating window. The report reviewed observational data from nearly 800,000 people who used either of two different TRE phone apps. The data showed that most people opted to start their daily eating during 11:00 AM-1:00 PM, and then stop during 6:00 PM-8:00 PM.

“TRE will not solve all of our obesity problems, but it’s a good place to start,” Dr. Gabel declared.

For people who include dinner at a typical evening time in their TRE window, a key message is that “dinner is your last food of the day. There’s no snacking later,” said Dr. Chow.

“The biggest challenge is adherence,” said Dr. Peterson. “Fewer people want to do TRE than you think. We know that calorie restriction works. We just need a way for people to do it,” and for at least some people, TRE is that way. While no evidence clearly shows that 8 hours is the best eating-window duration, “we think 8 hours is a good sweet-spot for motivated people,” she said.
 

Sparser data on TRE in people with T2D

Fewer studies have examined the impact of TRE on glycemic control, insulin sensitivity, and related effects in people with type 2 diabetes. According to Dr. Peterson, published reports currently include two randomized controlled studies and three single-arm studies in people with type 2 diabetes and an additional two studies in people with prediabetes.

The largest of these reports randomized 120 adults in China with type 2 diabetes and overweight to TRE using a 10-hour eating window (8:00 AM-6:00 PM) or unrestricted eating for 12 weeks. By the end of the study, those on the TRE regimen had an average reduction in their hemoglobin A1c from baseline that was 0.88 percentage points greater than among the controls, and the TRE arm had also lost an average of nearly 2.15 kg more from baseline than the controls.

Dr. Peterson highlighted the importance of expanding research using TRE in people with type 2 diabetes.

Dr. Peterson and Dr. Gabel report no relevant financial relationships. Dr. Chow has received research support from Dexcom.

A version of this article first appeared on Medscape.com.

Time-restricted eating (TRE) can be a practical, easy-to-follow way for some people to control their daily food intake and lose weight. It precludes a person’s need to pay close attention to how much they eat as long as they confine consumption to a limited time window. Plus, results from several recent studies show TRE can further benefit people with type 2 diabetes as well as obesity via mechanisms beyond weight loss.

The most tested and recommended eating window is 8 hours long, although periods up to roughly 10 hours may provide some benefits. Results from multiple studies document that TRE produces modest but consistent weight loss of less than 5% in many people. A recent meta-analysis of 17 randomized controlled studies involving 899 people showed an overall incremental weight loss, compared with controls of 1.60 kg on a TRE regimen.

The more limited data collected so far in people with type 2 diabetes show additional metabolic benefits from TRE, including improved beta-cell responsiveness, increased insulin sensitivity, nonoxidative glucose disposal, increased time in glycemic range, and virtually no hypoglycemic events, Courtney Peterson, PhD, said at the annual scientific sessions of the American Diabetes Association.

‘Eating earlier is better’

An advantage of TRE is that it is “agnostic to food preferences and quality,” said Lisa S. Chow, MD, during a separate session at the meeting. TRE “may have benefits beyond calorie restriction” that appear related to “the timing of eating and the extent of the eating window restriction. Eating earlier [in the day] is better” for markers of metabolic health regardless of how much weight a person may lose on a TRE regimen, noted Dr. Chow, an endocrinologist and professor at the University of Minnesota Medical School, Minneapolis.

But the TRE paradigm seems amenable to some flexibility on the timing for the eating window while still having benefit.

“Self-selected eating windows are usually late,” Dr. Chow observed, and because compliance with a constrained eating window matters, it may be worth allowing people to choose whichever time window for eating works best for them.

“If you let people pick their eating window, they typically include dinner,” said Dr. Chow, who has run a small TRE study that showed this.

“To maximize the effects [of TRE] people should use the eating window that best fits their life,” agreed Kelsey Gabel, PhD, who also gave a TRE talk during the meeting. “Eating most of your [daily] calories first thing in the morning would have the best cardiometabolic benefit, but reduced adherence would mitigate the benefit,” said Dr. Gabel, a nutrition researcher at the University of Illinois.
 

‘Meeting people where they’re at’

“We can have a larger public health impact by meeting people where they’re at. People should position their eating window where it best fits so they can achieve calorie restriction without even knowing it,” Dr. Gabel advised.

She cited a report as evidence that most people prefer a later eating window. The report reviewed observational data from nearly 800,000 people who used either of two different TRE phone apps. The data showed that most people opted to start their daily eating during 11:00 AM-1:00 PM, and then stop during 6:00 PM-8:00 PM.

“TRE will not solve all of our obesity problems, but it’s a good place to start,” Dr. Gabel declared.

For people who include dinner at a typical evening time in their TRE window, a key message is that “dinner is your last food of the day. There’s no snacking later,” said Dr. Chow.

“The biggest challenge is adherence,” said Dr. Peterson. “Fewer people want to do TRE than you think. We know that calorie restriction works. We just need a way for people to do it,” and for at least some people, TRE is that way. While no evidence clearly shows that 8 hours is the best eating-window duration, “we think 8 hours is a good sweet-spot for motivated people,” she said.
 

Sparser data on TRE in people with T2D

Fewer studies have examined the impact of TRE on glycemic control, insulin sensitivity, and related effects in people with type 2 diabetes. According to Dr. Peterson, published reports currently include two randomized controlled studies and three single-arm studies in people with type 2 diabetes and an additional two studies in people with prediabetes.

The largest of these reports randomized 120 adults in China with type 2 diabetes and overweight to TRE using a 10-hour eating window (8:00 AM-6:00 PM) or unrestricted eating for 12 weeks. By the end of the study, those on the TRE regimen had an average reduction in their hemoglobin A1c from baseline that was 0.88 percentage points greater than among the controls, and the TRE arm had also lost an average of nearly 2.15 kg more from baseline than the controls.

Dr. Peterson highlighted the importance of expanding research using TRE in people with type 2 diabetes.

Dr. Peterson and Dr. Gabel report no relevant financial relationships. Dr. Chow has received research support from Dexcom.

A version of this article first appeared on Medscape.com.

Time-restricted eating (TRE) can be a practical, easy-to-follow way for some people to control their daily food intake and lose weight. It precludes a person’s need to pay close attention to how much they eat as long as they confine consumption to a limited time window. Plus, results from several recent studies show TRE can further benefit people with type 2 diabetes as well as obesity via mechanisms beyond weight loss.

The most tested and recommended eating window is 8 hours long, although periods up to roughly 10 hours may provide some benefits. Results from multiple studies document that TRE produces modest but consistent weight loss of less than 5% in many people. A recent meta-analysis of 17 randomized controlled studies involving 899 people showed an overall incremental weight loss, compared with controls of 1.60 kg on a TRE regimen.

The more limited data collected so far in people with type 2 diabetes show additional metabolic benefits from TRE, including improved beta-cell responsiveness, increased insulin sensitivity, nonoxidative glucose disposal, increased time in glycemic range, and virtually no hypoglycemic events, Courtney Peterson, PhD, said at the annual scientific sessions of the American Diabetes Association.

‘Eating earlier is better’

An advantage of TRE is that it is “agnostic to food preferences and quality,” said Lisa S. Chow, MD, during a separate session at the meeting. TRE “may have benefits beyond calorie restriction” that appear related to “the timing of eating and the extent of the eating window restriction. Eating earlier [in the day] is better” for markers of metabolic health regardless of how much weight a person may lose on a TRE regimen, noted Dr. Chow, an endocrinologist and professor at the University of Minnesota Medical School, Minneapolis.

But the TRE paradigm seems amenable to some flexibility on the timing for the eating window while still having benefit.

“Self-selected eating windows are usually late,” Dr. Chow observed, and because compliance with a constrained eating window matters, it may be worth allowing people to choose whichever time window for eating works best for them.

“If you let people pick their eating window, they typically include dinner,” said Dr. Chow, who has run a small TRE study that showed this.

“To maximize the effects [of TRE] people should use the eating window that best fits their life,” agreed Kelsey Gabel, PhD, who also gave a TRE talk during the meeting. “Eating most of your [daily] calories first thing in the morning would have the best cardiometabolic benefit, but reduced adherence would mitigate the benefit,” said Dr. Gabel, a nutrition researcher at the University of Illinois.
 

‘Meeting people where they’re at’

“We can have a larger public health impact by meeting people where they’re at. People should position their eating window where it best fits so they can achieve calorie restriction without even knowing it,” Dr. Gabel advised.

She cited a report as evidence that most people prefer a later eating window. The report reviewed observational data from nearly 800,000 people who used either of two different TRE phone apps. The data showed that most people opted to start their daily eating during 11:00 AM-1:00 PM, and then stop during 6:00 PM-8:00 PM.

“TRE will not solve all of our obesity problems, but it’s a good place to start,” Dr. Gabel declared.

For people who include dinner at a typical evening time in their TRE window, a key message is that “dinner is your last food of the day. There’s no snacking later,” said Dr. Chow.

“The biggest challenge is adherence,” said Dr. Peterson. “Fewer people want to do TRE than you think. We know that calorie restriction works. We just need a way for people to do it,” and for at least some people, TRE is that way. While no evidence clearly shows that 8 hours is the best eating-window duration, “we think 8 hours is a good sweet-spot for motivated people,” she said.
 

Sparser data on TRE in people with T2D

Fewer studies have examined the impact of TRE on glycemic control, insulin sensitivity, and related effects in people with type 2 diabetes. According to Dr. Peterson, published reports currently include two randomized controlled studies and three single-arm studies in people with type 2 diabetes and an additional two studies in people with prediabetes.

The largest of these reports randomized 120 adults in China with type 2 diabetes and overweight to TRE using a 10-hour eating window (8:00 AM-6:00 PM) or unrestricted eating for 12 weeks. By the end of the study, those on the TRE regimen had an average reduction in their hemoglobin A1c from baseline that was 0.88 percentage points greater than among the controls, and the TRE arm had also lost an average of nearly 2.15 kg more from baseline than the controls.

Dr. Peterson highlighted the importance of expanding research using TRE in people with type 2 diabetes.

Dr. Peterson and Dr. Gabel report no relevant financial relationships. Dr. Chow has received research support from Dexcom.

A version of this article first appeared on Medscape.com.