Clinical Topics & News

As a field service representative for a slot machine company, Ryan Alexander, 37, of Louisville, Ky., spends his working hours in casinos, covering a large territory including Norfolk, Va., Indianapolis, and Charlotte. Social distancing in the casinos is not the norm. Despite all this up-close contact with people, he said he is still COVID-free, 3 years into the pandemic.

There was one nervous night when his temperature rose to 101° F, and he figured the virus had caught up with him. “I took a test and was fine,” he said, relieved that the result was negative. The fever disappeared, and he was back to normal soon. “Maybe it was just an exhausting day.”

Mr. Alexander is one of those people who have managed – or at least think they have managed – to avoid getting COVID-19.

He is, some say, a NOVID. While some scientists cringe at the term, it’s caught on to describe these virus super-dodgers. Online entrepreneurs offer NOVID-19 T-shirts, masks, and stickers, in case these super-healthy or super-lucky folks want to publicize their good luck. On Twitter, NOVIDs share stories of how they’ve done it.
 

How many NOVIDs?

As of March 16, according to the CDC, almost 104 million cases of COVID – about one-third of the U.S. population – have been reported, but many cases are known to go unreported. About half of American adults surveyed said they have had COVID, according to a December report by the COVID States Project, a multiuniversity effort to supply pandemic data.

As the numbers settle over time, though, it becomes clearer that some in the U.S. have apparently managed to avoid the virus.

While the exact number of people who have remained uninfected isn’t known with certainty, a review of comprehensive serologic data shows about 15% of Americans may not have gotten infected with COVID, Eric Topol, MD, editor-in-chief of Medscape (WebMD’s sister site for medical professionals) wrote in his substack Ground Truths.

But some scientists bristle at the term NOVIDs. They prefer the term “resisters,” according to Elena Hsieh, MD, associate professor of pediatrics and immunology at the University of Colorado at Denver, Aurora. Currently, she said, there is much more information on who is more susceptible to contracting severe COVID than who is resistant.

Dr. Hsieh is one of the regional coordinators for the COVID Human Genetic Effort, an international consortium of more than 250 researchers and doctors dedicated to discovering the genetic and immunological bases of the forms of SARS-CoV-2 infection. These researchers and others are looking for explanations for why some people get severe COVID while others seem resistant despite repeated exposure.
 

Resistance research

In determining explanations for resistance to infection, “the needle in the haystack that we are looking for is a change in the genetic code that would allow for you to avoid entry of the virus into the cell,” Dr. Hsieh said. “That is what being resistant to infection is.”

Part of the reason it’s so difficult to study resistance is defining a resister, she said. While many people consider themselves among that group because they’re been exposed multiple times – even with close family members infected and sick, yet they still felt fine – that doesn’t necessarily make them a resister, she said.

Those people could have been infected but remained without symptoms. “Resistance means the virus was inside you, it was near your cell and it did not infect your cell,” Dr. Hsieh said.

“I don’t think we know a lot so far,” Dr. Hsieh said about resisters. “I do believe that, just like there are genetic defects that make someone more susceptible, there are likely to be genetic defects that make somebody less susceptible.’’

“To identify genetic variants that are protective is a really challenging thing to do,” agreed Peter K. Gregersen, MD, professor of genetics at the Feinstein Institutes for Medical Research at Northwell Health in Manhasset, N.Y. Dr. Gregersen is also a regional coordinator for the COVID Human Genetic Effort.

He suspects the number found to be truly resistant to COVID – versus dodging it so far – is going to be very small or not found at all.

“It may exist for COVID or it may not,” he said. Some people may simply have what he calls a robust immune response in the upper part of the throat, perhaps killing off the virus quickly as soon as it enters, so they don’t get a positive test.

Genetic resistance has been found for other diseases, such as HIV.

“For HIV, scientists have been able to identify a specific gene that codes for a protein that can prevent individuals from getting infected,” said Sabrina Assoumou, MD, MPH, professor of medicine at Boston University, who researches HIV.

However, she said, “we haven’t yet found a similar gene or protein that can prevent people from getting infected with SARS-CoV-2.”

What has been found “is that some people might have a mutation in a gene that encodes for what’s called human leukocyte antigen (HLA),” Dr. Assoumou said. HLA, a molecule found on the surface of most cells, has a crucial role in the immune response to foreign substances. “A mutation in HLA can make people less likely to have symptoms if they get infected. Individuals still get infected, but they are less likely to have symptoms.”

Other research has found that those with food allergies are also less likely to be infected. The researchers have speculated that the inflammation characteristic of allergic conditions may reduce levels of a protein called the ACE2 receptor on the surface of airway cells. The SARS-CoV-2 virus uses the receptor to enter the cells, so if levels are low, that could reduce the ability of the virus to infect people.

The COVID Human Genetic Effort continues to search for participants, both those who were admitted to a hospital or repeatedly seen at a hospital because of COVID, as well as those who did not get infected, even after “intense and repeated” exposure.

The number of people likely to be resistant is much smaller, Dr. Hsieh said, than the number of people susceptible to severe disease.
 

The testing ... or lack thereof factor

The timing of testing and a person’s “infection profile” may be factors in people incorrectly declaring themselves NOVIDs, said Anne Wyllie, PhD, a research scientist in epidemiology at the Yale School of Public Health in New Haven, Conn., and a codeveloper of a saliva PCR test for COVID.

“Infection profiles can vary between individuals,” she said. For some, the infection may start in the lower respiratory tract, others in the higher respiratory tract. “Depending on where the virus takes up residence, that can affect test results.”

Then there’s the following-instructions factor. “It’s very likely that due to tests not being done at the right time, with the right sample, or not repeated if there is ongoing evidence of symptoms, that there are individuals out there who believe they are NOVIDs but just missed catching their infection at the window of opportunity.” Dr. Wyllie said.
 

Susceptibility research

“The part we have proven is the genetic defect that would make you more susceptible to having severe disease,” Dr. Hsieh said.

Many published papers report that inherited and/or autoimmune deficiencies of type I interferon immunity, important for combating viral infections and modulating the immune response, can be a significant cause of life-threatening COVID pneumonia.

More recently, researchers, including Jean-Laurent Casanova, MD, PhD, professor at Rockefeller University, New York, and cofounder of the COVID Human Genome Effort, reported that deficiencies in a gene that plays a role in built-in immunity (the early response), and a gene involved in signaling within the immune cells, impair interferon production and may be the basis of severe COVID pneumonia.
 

NOVIDs’ habits run the gamut

As scientists continue their research, the NOVIDs have their own ideas about why they’ve dodged the pandemic bullet, and they have a variety of approaches to handling the pandemic now.

Ryan Alexander, the field rep who travels to casinos, is up to date on his vaccinations and has gotten all the recommended COVID shots. “I was wearing a mask when told to wear masks,” he said.

He still observes the social distance habit but lives life. “I’ve been to three or four concerts in the past couple of years.”

And does he worry his number will eventually be up? “Not at this point, no,” he said.

Joe Asher, 46, said he has not gotten COVID despite being in contact with about 100 people a day, on average. He works as a bartender at an Evansville, Ind., brewery.

“On a Friday night, we can get 500 people,” he said. “I feel like almost everyone at the brewery got it. There’s no way I wasn’t exposed to it all the time.”

However, he said, his coworkers who did get sick were very cautious about not infecting others, partly to help protect a coworker’s family with newborn twins, so that may have helped him stay uninfected, too.

Mr. Asher said he’s in good physical shape, and he’s worked around the public for a long time, so figures maybe that has strengthened his immune system. He’s always been careful about handwashing and said he’s perhaps a bit more conscious of germs than others might be.

Roselyn Mena, 68, a retired teacher in Richmond, Calif., about 16 miles northeast of San Francisco, said she’s managed to avoid the virus even though her husband, Jesus Mena, got infected, as did her two adult children. Now, she remains vigilant about wearing a mask. She tries not to eat inside at restaurants. “I’m super careful,” she said.

Besides her teacher training, Ms. Mena had training as a medical assistant and learned a lot about sanitizing methods. She gets an annual flu shot, washes her hands often, and uses hand sanitizer.

When she shops, she will ask salespeople not wearing masks to please mask. “Only one refused, and she got someone else [to wait on her].”

One reason she is always careful about hygiene, Ms. Mena said, is that “when I get a cold, I get really sick. It last and lasts.” Now, she does worry she might still get it, she said, with the prospect of getting long COVID driving that worry.

In the beginning of the pandemic, Rhonda Fleming, 68, of Los Angeles, lived in a “COVID bubble,” interacting with just a few close family members. As cases went down, she enlarged the bubble. Her two grown daughters got infected, but her granddaughter did not.

She has been vigilant about masking, she said, “and I do still mask in public places.” She has a mask wardrobe, including basic black as well as glittery masks for dressier occasions. “I always carry a mask because inevitably, a cougher surrounds me.”

Now, she will bypass restaurants if she doesn’t feel comfortable with the environment, choosing ones with good air flow. When she flew to Mexico recently, she masked on the plane.

At this point, she said she doesn’t worry about getting infected but remains careful.

Recently, two friends, who have been as diligent as she has about precautions, got infected, “and they don’t know how they got it.”
 

Bragging rights?

Until researchers separate out the true resisters from those who claim to be, some NOVIDs are simply quietly grateful for their luck, while others mention their COVID-free status to anyone who asks or who will listen, and are proud of it. 

And what about those who wear a “NOVID” T-shirt?

“I would think they have a need to convey to the world they are different, perhaps special, because they beat COVID,” said Richard B. Joelson, a New York–based doctor of social work, a psychotherapist, and the author of Help Me! A Psychotherapist’s Tried-and-True Techniques for a Happier Relationship with Yourself and the People You Love. “They didn’t beat COVID, they just didn’t get it.”

Or they may be relieved they didn’t get sick, he said, because they feel defeated when they do. So “it’s a source of pride.” It might be the same people who tell anyone who will listen they never need a doctor or take no medicines, he said.

Even though science may prove many NOVIDs are inaccurate when they call themselves resisters, Dr. Hsieh understands the temptation to talk about it. “It’s kind of cool to think you are supernatural,” she said. “It’s much more attractive than being susceptible. It’s a lot sexier.” ■

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

As a field service representative for a slot machine company, Ryan Alexander, 37, of Louisville, Ky., spends his working hours in casinos, covering a large territory including Norfolk, Va., Indianapolis, and Charlotte. Social distancing in the casinos is not the norm. Despite all this up-close contact with people, he said he is still COVID-free, 3 years into the pandemic.

There was one nervous night when his temperature rose to 101° F, and he figured the virus had caught up with him. “I took a test and was fine,” he said, relieved that the result was negative. The fever disappeared, and he was back to normal soon. “Maybe it was just an exhausting day.”

Mr. Alexander is one of those people who have managed – or at least think they have managed – to avoid getting COVID-19.

He is, some say, a NOVID. While some scientists cringe at the term, it’s caught on to describe these virus super-dodgers. Online entrepreneurs offer NOVID-19 T-shirts, masks, and stickers, in case these super-healthy or super-lucky folks want to publicize their good luck. On Twitter, NOVIDs share stories of how they’ve done it.
 

How many NOVIDs?

As of March 16, according to the CDC, almost 104 million cases of COVID – about one-third of the U.S. population – have been reported, but many cases are known to go unreported. About half of American adults surveyed said they have had COVID, according to a December report by the COVID States Project, a multiuniversity effort to supply pandemic data.

As the numbers settle over time, though, it becomes clearer that some in the U.S. have apparently managed to avoid the virus.

While the exact number of people who have remained uninfected isn’t known with certainty, a review of comprehensive serologic data shows about 15% of Americans may not have gotten infected with COVID, Eric Topol, MD, editor-in-chief of Medscape (WebMD’s sister site for medical professionals) wrote in his substack Ground Truths.

But some scientists bristle at the term NOVIDs. They prefer the term “resisters,” according to Elena Hsieh, MD, associate professor of pediatrics and immunology at the University of Colorado at Denver, Aurora. Currently, she said, there is much more information on who is more susceptible to contracting severe COVID than who is resistant.

Dr. Hsieh is one of the regional coordinators for the COVID Human Genetic Effort, an international consortium of more than 250 researchers and doctors dedicated to discovering the genetic and immunological bases of the forms of SARS-CoV-2 infection. These researchers and others are looking for explanations for why some people get severe COVID while others seem resistant despite repeated exposure.
 

Resistance research

In determining explanations for resistance to infection, “the needle in the haystack that we are looking for is a change in the genetic code that would allow for you to avoid entry of the virus into the cell,” Dr. Hsieh said. “That is what being resistant to infection is.”

Part of the reason it’s so difficult to study resistance is defining a resister, she said. While many people consider themselves among that group because they’re been exposed multiple times – even with close family members infected and sick, yet they still felt fine – that doesn’t necessarily make them a resister, she said.

Those people could have been infected but remained without symptoms. “Resistance means the virus was inside you, it was near your cell and it did not infect your cell,” Dr. Hsieh said.

“I don’t think we know a lot so far,” Dr. Hsieh said about resisters. “I do believe that, just like there are genetic defects that make someone more susceptible, there are likely to be genetic defects that make somebody less susceptible.’’

“To identify genetic variants that are protective is a really challenging thing to do,” agreed Peter K. Gregersen, MD, professor of genetics at the Feinstein Institutes for Medical Research at Northwell Health in Manhasset, N.Y. Dr. Gregersen is also a regional coordinator for the COVID Human Genetic Effort.

He suspects the number found to be truly resistant to COVID – versus dodging it so far – is going to be very small or not found at all.

“It may exist for COVID or it may not,” he said. Some people may simply have what he calls a robust immune response in the upper part of the throat, perhaps killing off the virus quickly as soon as it enters, so they don’t get a positive test.

Genetic resistance has been found for other diseases, such as HIV.

“For HIV, scientists have been able to identify a specific gene that codes for a protein that can prevent individuals from getting infected,” said Sabrina Assoumou, MD, MPH, professor of medicine at Boston University, who researches HIV.

However, she said, “we haven’t yet found a similar gene or protein that can prevent people from getting infected with SARS-CoV-2.”

What has been found “is that some people might have a mutation in a gene that encodes for what’s called human leukocyte antigen (HLA),” Dr. Assoumou said. HLA, a molecule found on the surface of most cells, has a crucial role in the immune response to foreign substances. “A mutation in HLA can make people less likely to have symptoms if they get infected. Individuals still get infected, but they are less likely to have symptoms.”

Other research has found that those with food allergies are also less likely to be infected. The researchers have speculated that the inflammation characteristic of allergic conditions may reduce levels of a protein called the ACE2 receptor on the surface of airway cells. The SARS-CoV-2 virus uses the receptor to enter the cells, so if levels are low, that could reduce the ability of the virus to infect people.

The COVID Human Genetic Effort continues to search for participants, both those who were admitted to a hospital or repeatedly seen at a hospital because of COVID, as well as those who did not get infected, even after “intense and repeated” exposure.

The number of people likely to be resistant is much smaller, Dr. Hsieh said, than the number of people susceptible to severe disease.
 

The testing ... or lack thereof factor

The timing of testing and a person’s “infection profile” may be factors in people incorrectly declaring themselves NOVIDs, said Anne Wyllie, PhD, a research scientist in epidemiology at the Yale School of Public Health in New Haven, Conn., and a codeveloper of a saliva PCR test for COVID.

“Infection profiles can vary between individuals,” she said. For some, the infection may start in the lower respiratory tract, others in the higher respiratory tract. “Depending on where the virus takes up residence, that can affect test results.”

Then there’s the following-instructions factor. “It’s very likely that due to tests not being done at the right time, with the right sample, or not repeated if there is ongoing evidence of symptoms, that there are individuals out there who believe they are NOVIDs but just missed catching their infection at the window of opportunity.” Dr. Wyllie said.
 

Susceptibility research

“The part we have proven is the genetic defect that would make you more susceptible to having severe disease,” Dr. Hsieh said.

Many published papers report that inherited and/or autoimmune deficiencies of type I interferon immunity, important for combating viral infections and modulating the immune response, can be a significant cause of life-threatening COVID pneumonia.

More recently, researchers, including Jean-Laurent Casanova, MD, PhD, professor at Rockefeller University, New York, and cofounder of the COVID Human Genome Effort, reported that deficiencies in a gene that plays a role in built-in immunity (the early response), and a gene involved in signaling within the immune cells, impair interferon production and may be the basis of severe COVID pneumonia.
 

NOVIDs’ habits run the gamut

As scientists continue their research, the NOVIDs have their own ideas about why they’ve dodged the pandemic bullet, and they have a variety of approaches to handling the pandemic now.

Ryan Alexander, the field rep who travels to casinos, is up to date on his vaccinations and has gotten all the recommended COVID shots. “I was wearing a mask when told to wear masks,” he said.

He still observes the social distance habit but lives life. “I’ve been to three or four concerts in the past couple of years.”

And does he worry his number will eventually be up? “Not at this point, no,” he said.

Joe Asher, 46, said he has not gotten COVID despite being in contact with about 100 people a day, on average. He works as a bartender at an Evansville, Ind., brewery.

“On a Friday night, we can get 500 people,” he said. “I feel like almost everyone at the brewery got it. There’s no way I wasn’t exposed to it all the time.”

However, he said, his coworkers who did get sick were very cautious about not infecting others, partly to help protect a coworker’s family with newborn twins, so that may have helped him stay uninfected, too.

Mr. Asher said he’s in good physical shape, and he’s worked around the public for a long time, so figures maybe that has strengthened his immune system. He’s always been careful about handwashing and said he’s perhaps a bit more conscious of germs than others might be.

Roselyn Mena, 68, a retired teacher in Richmond, Calif., about 16 miles northeast of San Francisco, said she’s managed to avoid the virus even though her husband, Jesus Mena, got infected, as did her two adult children. Now, she remains vigilant about wearing a mask. She tries not to eat inside at restaurants. “I’m super careful,” she said.

Besides her teacher training, Ms. Mena had training as a medical assistant and learned a lot about sanitizing methods. She gets an annual flu shot, washes her hands often, and uses hand sanitizer.

When she shops, she will ask salespeople not wearing masks to please mask. “Only one refused, and she got someone else [to wait on her].”

One reason she is always careful about hygiene, Ms. Mena said, is that “when I get a cold, I get really sick. It last and lasts.” Now, she does worry she might still get it, she said, with the prospect of getting long COVID driving that worry.

In the beginning of the pandemic, Rhonda Fleming, 68, of Los Angeles, lived in a “COVID bubble,” interacting with just a few close family members. As cases went down, she enlarged the bubble. Her two grown daughters got infected, but her granddaughter did not.

She has been vigilant about masking, she said, “and I do still mask in public places.” She has a mask wardrobe, including basic black as well as glittery masks for dressier occasions. “I always carry a mask because inevitably, a cougher surrounds me.”

Now, she will bypass restaurants if she doesn’t feel comfortable with the environment, choosing ones with good air flow. When she flew to Mexico recently, she masked on the plane.

At this point, she said she doesn’t worry about getting infected but remains careful.

Recently, two friends, who have been as diligent as she has about precautions, got infected, “and they don’t know how they got it.”
 

Bragging rights?

Until researchers separate out the true resisters from those who claim to be, some NOVIDs are simply quietly grateful for their luck, while others mention their COVID-free status to anyone who asks or who will listen, and are proud of it. 

And what about those who wear a “NOVID” T-shirt?

“I would think they have a need to convey to the world they are different, perhaps special, because they beat COVID,” said Richard B. Joelson, a New York–based doctor of social work, a psychotherapist, and the author of Help Me! A Psychotherapist’s Tried-and-True Techniques for a Happier Relationship with Yourself and the People You Love. “They didn’t beat COVID, they just didn’t get it.”

Or they may be relieved they didn’t get sick, he said, because they feel defeated when they do. So “it’s a source of pride.” It might be the same people who tell anyone who will listen they never need a doctor or take no medicines, he said.

Even though science may prove many NOVIDs are inaccurate when they call themselves resisters, Dr. Hsieh understands the temptation to talk about it. “It’s kind of cool to think you are supernatural,” she said. “It’s much more attractive than being susceptible. It’s a lot sexier.” ■

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

As a field service representative for a slot machine company, Ryan Alexander, 37, of Louisville, Ky., spends his working hours in casinos, covering a large territory including Norfolk, Va., Indianapolis, and Charlotte. Social distancing in the casinos is not the norm. Despite all this up-close contact with people, he said he is still COVID-free, 3 years into the pandemic.

There was one nervous night when his temperature rose to 101° F, and he figured the virus had caught up with him. “I took a test and was fine,” he said, relieved that the result was negative. The fever disappeared, and he was back to normal soon. “Maybe it was just an exhausting day.”

Mr. Alexander is one of those people who have managed – or at least think they have managed – to avoid getting COVID-19.

He is, some say, a NOVID. While some scientists cringe at the term, it’s caught on to describe these virus super-dodgers. Online entrepreneurs offer NOVID-19 T-shirts, masks, and stickers, in case these super-healthy or super-lucky folks want to publicize their good luck. On Twitter, NOVIDs share stories of how they’ve done it.
 

How many NOVIDs?

As of March 16, according to the CDC, almost 104 million cases of COVID – about one-third of the U.S. population – have been reported, but many cases are known to go unreported. About half of American adults surveyed said they have had COVID, according to a December report by the COVID States Project, a multiuniversity effort to supply pandemic data.

As the numbers settle over time, though, it becomes clearer that some in the U.S. have apparently managed to avoid the virus.

While the exact number of people who have remained uninfected isn’t known with certainty, a review of comprehensive serologic data shows about 15% of Americans may not have gotten infected with COVID, Eric Topol, MD, editor-in-chief of Medscape (WebMD’s sister site for medical professionals) wrote in his substack Ground Truths.

But some scientists bristle at the term NOVIDs. They prefer the term “resisters,” according to Elena Hsieh, MD, associate professor of pediatrics and immunology at the University of Colorado at Denver, Aurora. Currently, she said, there is much more information on who is more susceptible to contracting severe COVID than who is resistant.

Dr. Hsieh is one of the regional coordinators for the COVID Human Genetic Effort, an international consortium of more than 250 researchers and doctors dedicated to discovering the genetic and immunological bases of the forms of SARS-CoV-2 infection. These researchers and others are looking for explanations for why some people get severe COVID while others seem resistant despite repeated exposure.
 

Resistance research

In determining explanations for resistance to infection, “the needle in the haystack that we are looking for is a change in the genetic code that would allow for you to avoid entry of the virus into the cell,” Dr. Hsieh said. “That is what being resistant to infection is.”

Part of the reason it’s so difficult to study resistance is defining a resister, she said. While many people consider themselves among that group because they’re been exposed multiple times – even with close family members infected and sick, yet they still felt fine – that doesn’t necessarily make them a resister, she said.

Those people could have been infected but remained without symptoms. “Resistance means the virus was inside you, it was near your cell and it did not infect your cell,” Dr. Hsieh said.

“I don’t think we know a lot so far,” Dr. Hsieh said about resisters. “I do believe that, just like there are genetic defects that make someone more susceptible, there are likely to be genetic defects that make somebody less susceptible.’’

“To identify genetic variants that are protective is a really challenging thing to do,” agreed Peter K. Gregersen, MD, professor of genetics at the Feinstein Institutes for Medical Research at Northwell Health in Manhasset, N.Y. Dr. Gregersen is also a regional coordinator for the COVID Human Genetic Effort.

He suspects the number found to be truly resistant to COVID – versus dodging it so far – is going to be very small or not found at all.

“It may exist for COVID or it may not,” he said. Some people may simply have what he calls a robust immune response in the upper part of the throat, perhaps killing off the virus quickly as soon as it enters, so they don’t get a positive test.

Genetic resistance has been found for other diseases, such as HIV.

“For HIV, scientists have been able to identify a specific gene that codes for a protein that can prevent individuals from getting infected,” said Sabrina Assoumou, MD, MPH, professor of medicine at Boston University, who researches HIV.

However, she said, “we haven’t yet found a similar gene or protein that can prevent people from getting infected with SARS-CoV-2.”

What has been found “is that some people might have a mutation in a gene that encodes for what’s called human leukocyte antigen (HLA),” Dr. Assoumou said. HLA, a molecule found on the surface of most cells, has a crucial role in the immune response to foreign substances. “A mutation in HLA can make people less likely to have symptoms if they get infected. Individuals still get infected, but they are less likely to have symptoms.”

Other research has found that those with food allergies are also less likely to be infected. The researchers have speculated that the inflammation characteristic of allergic conditions may reduce levels of a protein called the ACE2 receptor on the surface of airway cells. The SARS-CoV-2 virus uses the receptor to enter the cells, so if levels are low, that could reduce the ability of the virus to infect people.

The COVID Human Genetic Effort continues to search for participants, both those who were admitted to a hospital or repeatedly seen at a hospital because of COVID, as well as those who did not get infected, even after “intense and repeated” exposure.

The number of people likely to be resistant is much smaller, Dr. Hsieh said, than the number of people susceptible to severe disease.
 

The testing ... or lack thereof factor

The timing of testing and a person’s “infection profile” may be factors in people incorrectly declaring themselves NOVIDs, said Anne Wyllie, PhD, a research scientist in epidemiology at the Yale School of Public Health in New Haven, Conn., and a codeveloper of a saliva PCR test for COVID.

“Infection profiles can vary between individuals,” she said. For some, the infection may start in the lower respiratory tract, others in the higher respiratory tract. “Depending on where the virus takes up residence, that can affect test results.”

Then there’s the following-instructions factor. “It’s very likely that due to tests not being done at the right time, with the right sample, or not repeated if there is ongoing evidence of symptoms, that there are individuals out there who believe they are NOVIDs but just missed catching their infection at the window of opportunity.” Dr. Wyllie said.
 

Susceptibility research

“The part we have proven is the genetic defect that would make you more susceptible to having severe disease,” Dr. Hsieh said.

Many published papers report that inherited and/or autoimmune deficiencies of type I interferon immunity, important for combating viral infections and modulating the immune response, can be a significant cause of life-threatening COVID pneumonia.

More recently, researchers, including Jean-Laurent Casanova, MD, PhD, professor at Rockefeller University, New York, and cofounder of the COVID Human Genome Effort, reported that deficiencies in a gene that plays a role in built-in immunity (the early response), and a gene involved in signaling within the immune cells, impair interferon production and may be the basis of severe COVID pneumonia.
 

NOVIDs’ habits run the gamut

As scientists continue their research, the NOVIDs have their own ideas about why they’ve dodged the pandemic bullet, and they have a variety of approaches to handling the pandemic now.

Ryan Alexander, the field rep who travels to casinos, is up to date on his vaccinations and has gotten all the recommended COVID shots. “I was wearing a mask when told to wear masks,” he said.

He still observes the social distance habit but lives life. “I’ve been to three or four concerts in the past couple of years.”

And does he worry his number will eventually be up? “Not at this point, no,” he said.

Joe Asher, 46, said he has not gotten COVID despite being in contact with about 100 people a day, on average. He works as a bartender at an Evansville, Ind., brewery.

“On a Friday night, we can get 500 people,” he said. “I feel like almost everyone at the brewery got it. There’s no way I wasn’t exposed to it all the time.”

However, he said, his coworkers who did get sick were very cautious about not infecting others, partly to help protect a coworker’s family with newborn twins, so that may have helped him stay uninfected, too.

Mr. Asher said he’s in good physical shape, and he’s worked around the public for a long time, so figures maybe that has strengthened his immune system. He’s always been careful about handwashing and said he’s perhaps a bit more conscious of germs than others might be.

Roselyn Mena, 68, a retired teacher in Richmond, Calif., about 16 miles northeast of San Francisco, said she’s managed to avoid the virus even though her husband, Jesus Mena, got infected, as did her two adult children. Now, she remains vigilant about wearing a mask. She tries not to eat inside at restaurants. “I’m super careful,” she said.

Besides her teacher training, Ms. Mena had training as a medical assistant and learned a lot about sanitizing methods. She gets an annual flu shot, washes her hands often, and uses hand sanitizer.

When she shops, she will ask salespeople not wearing masks to please mask. “Only one refused, and she got someone else [to wait on her].”

One reason she is always careful about hygiene, Ms. Mena said, is that “when I get a cold, I get really sick. It last and lasts.” Now, she does worry she might still get it, she said, with the prospect of getting long COVID driving that worry.

In the beginning of the pandemic, Rhonda Fleming, 68, of Los Angeles, lived in a “COVID bubble,” interacting with just a few close family members. As cases went down, she enlarged the bubble. Her two grown daughters got infected, but her granddaughter did not.

She has been vigilant about masking, she said, “and I do still mask in public places.” She has a mask wardrobe, including basic black as well as glittery masks for dressier occasions. “I always carry a mask because inevitably, a cougher surrounds me.”

Now, she will bypass restaurants if she doesn’t feel comfortable with the environment, choosing ones with good air flow. When she flew to Mexico recently, she masked on the plane.

At this point, she said she doesn’t worry about getting infected but remains careful.

Recently, two friends, who have been as diligent as she has about precautions, got infected, “and they don’t know how they got it.”
 

Bragging rights?

Until researchers separate out the true resisters from those who claim to be, some NOVIDs are simply quietly grateful for their luck, while others mention their COVID-free status to anyone who asks or who will listen, and are proud of it. 

And what about those who wear a “NOVID” T-shirt?

“I would think they have a need to convey to the world they are different, perhaps special, because they beat COVID,” said Richard B. Joelson, a New York–based doctor of social work, a psychotherapist, and the author of Help Me! A Psychotherapist’s Tried-and-True Techniques for a Happier Relationship with Yourself and the People You Love. “They didn’t beat COVID, they just didn’t get it.”

Or they may be relieved they didn’t get sick, he said, because they feel defeated when they do. So “it’s a source of pride.” It might be the same people who tell anyone who will listen they never need a doctor or take no medicines, he said.

Even though science may prove many NOVIDs are inaccurate when they call themselves resisters, Dr. Hsieh understands the temptation to talk about it. “It’s kind of cool to think you are supernatural,” she said. “It’s much more attractive than being susceptible. It’s a lot sexier.” ■

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

High total intake of ultraprocessed food (UPF) is associated with an increased risk of developing type 2 diabetes, suggests a large-scale analysis that nevertheless revealed that the risk applies only to certain such foods.

Courtesy National Cancer Institute

The research was recently published in Diabetes Care by Zhangling Chen, PhD, Erasmus MC Rotterdam, Netherlands, and colleagues.

Examining almost 200,000 participants in three U.S. studies, yielding more than 5 million person-years of follow-up, the scientists found that high intake of UPF was associated with a 28% increased risk of type 2 diabetes, after statistical adjustments.

However, the increased risk was restricted to certain UPFs, including ready meals, refined breads, sweetened beverages, and sauces and condiments, with other foods considered UPFs, such as cereals, dark- and whole grain breads, and packaged sweet and savory snacks, among others, associated with a reduced risk of diabetes.

Senior author Jean-Philippe Drouin-Chartier, PhD, Nutrition Center, Laval University, Quebec City, told this news organization: “While whole grain breads can be considered as ultraprocessed foods, their consumption should not be discouraged. In our study, we observed that whole grain breads consumption is inversely associated with type 2 diabetes risk. This is supported by many studies linking dietary fiber consumption to better cardiometabolic health.”
 

Ultraprocessed food intake higher in the U.S. than in Europe

The researchers note that a handful of European studies have also reported an association between UPF consumption and increased type 2 diabetes risk, with the effect ranging from 15% to 53%, depending on the level of intake and the cohort of patients studied.

They note, however, that total UPF intake in the U.S. is “much higher than in Europe,” particularly in the case of ultraprocessed breads and cereals and artificially or sugar-sweetened beverages.

In the current study, they examined data on 71,781 women from the Nurses’ Health Study, 87,918 women from the NHS II, and 38,847 men from the Health Professional Follow-up Study, none of whom had cardiovascular disease, cancer, or diabetes at baseline.

In all three studies, questionnaires were administered every 2 years to collect demographic, lifestyle, and medical information, and a validated food frequency questionnaire was used every 2-4 years to assess participants’ diets over 30 years of follow-up.

Using the NOVA Food Classification system, the items on the food frequency questionnaire were categorized into one of four groups: unprocessed or minimally processed foods; processed culinary ingredients; processed foods; or UPFs, which were subdivided into nine mutually exclusive subgroups.

Servings per day were then used to determine individual UPF intake.

Higher total UPF intake was associated with a greater total energy intake, body mass index, and prevalence of hypercholesterolemia and/or hypertension, as well as lower healthy eating scores and physical activity.

The researchers calculated that, over 5,187,678 person-years of follow-up, there were 19,503 cases of type 2 diabetes across the three study cohorts.

Multivariate analysis taking into consideration a range of potential risk factors, including BMI, revealed that, across the three study cohorts, the highest quintile of UPF intake was associated with a significantly increased risk of type 2 diabetes.

Compared with the lowest quintile of UPF intake, the hazard ratio for incident type 2 diabetes was 1.28 (P < .0001), with an increase in risk per additional serving per day of 3%.

The UPFs associated with a higher type 2 diabetes risk were as previously described and also included animal-based products and ready-to-eat mixed dishes.

In contrast, intake of UPFs including cereals, dark and whole grain breads, packaged sweet and savory snacks, fruit-based products, and yogurt and dairy-based desserts were linked to a reduced risk of type 2 diabetes.

Then to further validate their findings, the researchers conducted a meta-analysis of their own and four additional studies, comprising 415,554 participants and 21,932 events, with a follow-up of 3.4-32.0 years.

They determined that the pooled relative risk of type 2 diabetes with the highest versus lowest levels of UPF consumption was 1.40, with each 10% increase in total UPF intake associated with a 12% increase in diabetes risk.
 

Ideal is to have access to minimally processed foods

The NOVA food classification system states that UPFs are industrial formulations “made mostly or entirely with substances extracted from foods, often chemically modified, with additives and with little, if any, whole foods added.”

A recent study questioned the value of the NOVA classification after finding that it had “low consistency” when assigning foods.

Previous studies have nevertheless revealed that UPFs and their constituents negatively affect the gut microbiota and can cause systemic inflammation, insulin resistance, and increased body weight.

Dr. Drouin-Chartier concluded: “There is a need to facilitate ... access to minimally processed foods. This encompasses [appropriate] pricing and physical access [to such foods], that is, addressing the issue of food deserts.”

The NHS I and II and HPFS studies are supported by National Institutes of Health. Dr. Drouin-Chartier has reported a relationship with the Dairy Farmers of Canada. No other financial relationships were declared.

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

High total intake of ultraprocessed food (UPF) is associated with an increased risk of developing type 2 diabetes, suggests a large-scale analysis that nevertheless revealed that the risk applies only to certain such foods.

Courtesy National Cancer Institute

The research was recently published in Diabetes Care by Zhangling Chen, PhD, Erasmus MC Rotterdam, Netherlands, and colleagues.

Examining almost 200,000 participants in three U.S. studies, yielding more than 5 million person-years of follow-up, the scientists found that high intake of UPF was associated with a 28% increased risk of type 2 diabetes, after statistical adjustments.

However, the increased risk was restricted to certain UPFs, including ready meals, refined breads, sweetened beverages, and sauces and condiments, with other foods considered UPFs, such as cereals, dark- and whole grain breads, and packaged sweet and savory snacks, among others, associated with a reduced risk of diabetes.

Senior author Jean-Philippe Drouin-Chartier, PhD, Nutrition Center, Laval University, Quebec City, told this news organization: “While whole grain breads can be considered as ultraprocessed foods, their consumption should not be discouraged. In our study, we observed that whole grain breads consumption is inversely associated with type 2 diabetes risk. This is supported by many studies linking dietary fiber consumption to better cardiometabolic health.”
 

Ultraprocessed food intake higher in the U.S. than in Europe

The researchers note that a handful of European studies have also reported an association between UPF consumption and increased type 2 diabetes risk, with the effect ranging from 15% to 53%, depending on the level of intake and the cohort of patients studied.

They note, however, that total UPF intake in the U.S. is “much higher than in Europe,” particularly in the case of ultraprocessed breads and cereals and artificially or sugar-sweetened beverages.

In the current study, they examined data on 71,781 women from the Nurses’ Health Study, 87,918 women from the NHS II, and 38,847 men from the Health Professional Follow-up Study, none of whom had cardiovascular disease, cancer, or diabetes at baseline.

In all three studies, questionnaires were administered every 2 years to collect demographic, lifestyle, and medical information, and a validated food frequency questionnaire was used every 2-4 years to assess participants’ diets over 30 years of follow-up.

Using the NOVA Food Classification system, the items on the food frequency questionnaire were categorized into one of four groups: unprocessed or minimally processed foods; processed culinary ingredients; processed foods; or UPFs, which were subdivided into nine mutually exclusive subgroups.

Servings per day were then used to determine individual UPF intake.

Higher total UPF intake was associated with a greater total energy intake, body mass index, and prevalence of hypercholesterolemia and/or hypertension, as well as lower healthy eating scores and physical activity.

The researchers calculated that, over 5,187,678 person-years of follow-up, there were 19,503 cases of type 2 diabetes across the three study cohorts.

Multivariate analysis taking into consideration a range of potential risk factors, including BMI, revealed that, across the three study cohorts, the highest quintile of UPF intake was associated with a significantly increased risk of type 2 diabetes.

Compared with the lowest quintile of UPF intake, the hazard ratio for incident type 2 diabetes was 1.28 (P < .0001), with an increase in risk per additional serving per day of 3%.

The UPFs associated with a higher type 2 diabetes risk were as previously described and also included animal-based products and ready-to-eat mixed dishes.

In contrast, intake of UPFs including cereals, dark and whole grain breads, packaged sweet and savory snacks, fruit-based products, and yogurt and dairy-based desserts were linked to a reduced risk of type 2 diabetes.

Then to further validate their findings, the researchers conducted a meta-analysis of their own and four additional studies, comprising 415,554 participants and 21,932 events, with a follow-up of 3.4-32.0 years.

They determined that the pooled relative risk of type 2 diabetes with the highest versus lowest levels of UPF consumption was 1.40, with each 10% increase in total UPF intake associated with a 12% increase in diabetes risk.
 

Ideal is to have access to minimally processed foods

The NOVA food classification system states that UPFs are industrial formulations “made mostly or entirely with substances extracted from foods, often chemically modified, with additives and with little, if any, whole foods added.”

A recent study questioned the value of the NOVA classification after finding that it had “low consistency” when assigning foods.

Previous studies have nevertheless revealed that UPFs and their constituents negatively affect the gut microbiota and can cause systemic inflammation, insulin resistance, and increased body weight.

Dr. Drouin-Chartier concluded: “There is a need to facilitate ... access to minimally processed foods. This encompasses [appropriate] pricing and physical access [to such foods], that is, addressing the issue of food deserts.”

The NHS I and II and HPFS studies are supported by National Institutes of Health. Dr. Drouin-Chartier has reported a relationship with the Dairy Farmers of Canada. No other financial relationships were declared.

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

High total intake of ultraprocessed food (UPF) is associated with an increased risk of developing type 2 diabetes, suggests a large-scale analysis that nevertheless revealed that the risk applies only to certain such foods.

Courtesy National Cancer Institute

The research was recently published in Diabetes Care by Zhangling Chen, PhD, Erasmus MC Rotterdam, Netherlands, and colleagues.

Examining almost 200,000 participants in three U.S. studies, yielding more than 5 million person-years of follow-up, the scientists found that high intake of UPF was associated with a 28% increased risk of type 2 diabetes, after statistical adjustments.

However, the increased risk was restricted to certain UPFs, including ready meals, refined breads, sweetened beverages, and sauces and condiments, with other foods considered UPFs, such as cereals, dark- and whole grain breads, and packaged sweet and savory snacks, among others, associated with a reduced risk of diabetes.

Senior author Jean-Philippe Drouin-Chartier, PhD, Nutrition Center, Laval University, Quebec City, told this news organization: “While whole grain breads can be considered as ultraprocessed foods, their consumption should not be discouraged. In our study, we observed that whole grain breads consumption is inversely associated with type 2 diabetes risk. This is supported by many studies linking dietary fiber consumption to better cardiometabolic health.”
 

Ultraprocessed food intake higher in the U.S. than in Europe

The researchers note that a handful of European studies have also reported an association between UPF consumption and increased type 2 diabetes risk, with the effect ranging from 15% to 53%, depending on the level of intake and the cohort of patients studied.

They note, however, that total UPF intake in the U.S. is “much higher than in Europe,” particularly in the case of ultraprocessed breads and cereals and artificially or sugar-sweetened beverages.

In the current study, they examined data on 71,781 women from the Nurses’ Health Study, 87,918 women from the NHS II, and 38,847 men from the Health Professional Follow-up Study, none of whom had cardiovascular disease, cancer, or diabetes at baseline.

In all three studies, questionnaires were administered every 2 years to collect demographic, lifestyle, and medical information, and a validated food frequency questionnaire was used every 2-4 years to assess participants’ diets over 30 years of follow-up.

Using the NOVA Food Classification system, the items on the food frequency questionnaire were categorized into one of four groups: unprocessed or minimally processed foods; processed culinary ingredients; processed foods; or UPFs, which were subdivided into nine mutually exclusive subgroups.

Servings per day were then used to determine individual UPF intake.

Higher total UPF intake was associated with a greater total energy intake, body mass index, and prevalence of hypercholesterolemia and/or hypertension, as well as lower healthy eating scores and physical activity.

The researchers calculated that, over 5,187,678 person-years of follow-up, there were 19,503 cases of type 2 diabetes across the three study cohorts.

Multivariate analysis taking into consideration a range of potential risk factors, including BMI, revealed that, across the three study cohorts, the highest quintile of UPF intake was associated with a significantly increased risk of type 2 diabetes.

Compared with the lowest quintile of UPF intake, the hazard ratio for incident type 2 diabetes was 1.28 (P < .0001), with an increase in risk per additional serving per day of 3%.

The UPFs associated with a higher type 2 diabetes risk were as previously described and also included animal-based products and ready-to-eat mixed dishes.

In contrast, intake of UPFs including cereals, dark and whole grain breads, packaged sweet and savory snacks, fruit-based products, and yogurt and dairy-based desserts were linked to a reduced risk of type 2 diabetes.

Then to further validate their findings, the researchers conducted a meta-analysis of their own and four additional studies, comprising 415,554 participants and 21,932 events, with a follow-up of 3.4-32.0 years.

They determined that the pooled relative risk of type 2 diabetes with the highest versus lowest levels of UPF consumption was 1.40, with each 10% increase in total UPF intake associated with a 12% increase in diabetes risk.
 

Ideal is to have access to minimally processed foods

The NOVA food classification system states that UPFs are industrial formulations “made mostly or entirely with substances extracted from foods, often chemically modified, with additives and with little, if any, whole foods added.”

A recent study questioned the value of the NOVA classification after finding that it had “low consistency” when assigning foods.

Previous studies have nevertheless revealed that UPFs and their constituents negatively affect the gut microbiota and can cause systemic inflammation, insulin resistance, and increased body weight.

Dr. Drouin-Chartier concluded: “There is a need to facilitate ... access to minimally processed foods. This encompasses [appropriate] pricing and physical access [to such foods], that is, addressing the issue of food deserts.”

The NHS I and II and HPFS studies are supported by National Institutes of Health. Dr. Drouin-Chartier has reported a relationship with the Dairy Farmers of Canada. No other financial relationships were declared.

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

Higher blood caffeine levels appear to reduce the risks for both adiposity and type 2 diabetes, the results of a new study suggest.

Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.

In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.

The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.

The work was published online March 14 in BMJ Medicine.

“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.

“It does not, however, prove cause and effect.”

The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”

Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”

“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.

Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.

Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m² in BMI (P < .001).

For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).

Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).

Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).

Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.

They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).

The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.

“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.

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

Higher blood caffeine levels appear to reduce the risks for both adiposity and type 2 diabetes, the results of a new study suggest.

Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.

In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.

The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.

The work was published online March 14 in BMJ Medicine.

“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.

“It does not, however, prove cause and effect.”

The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”

Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”

“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.

Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.

Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m² in BMI (P < .001).

For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).

Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).

Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).

Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.

They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).

The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.

“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.

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

Higher blood caffeine levels appear to reduce the risks for both adiposity and type 2 diabetes, the results of a new study suggest.

Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.

In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.

The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.

The work was published online March 14 in BMJ Medicine.

“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.

“It does not, however, prove cause and effect.”

The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”

Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”

“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.

Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.

Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m² in BMI (P < .001).

For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).

Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).

Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).

Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.

They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).

The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.

“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.

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

Adults with type 2 diabetes treated with an SGLT2 inhibitor had roughly a third fewer episodes of acute kidney injury (AKI) compared with matched people with type 2 diabetes treated with a DPP4 inhibitor, in an analysis of health insurance data from more than 100,000 Taiwan residents during 2016-2018.

The findings add to, and expand on, prior evidence that treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class cuts the incidence of AKI, say the authors of the report, which was recently published in JAMA Network Open.

The long-term risk for AKI among people with type 2 diabetes treated with an SGLT2 inhibitor “appears to be quite low” compared with adults who received an agent from the dipeptidyl peptidase 4 (DPP4) inhibitor class.

Treatment with an SGLT2 inhibitor – such as canagliflozin (Invokana), dapagliflozin (Farxiga), or empagliflozin (Jardiance) – causes a transient drop in kidney function that manifests as a temporary dip in estimated glomerular filtration rate, which caused concerns about AKI when the drugs were first introduced.

Indeed, canagliflozin and dapagliflozin had warnings strengthened 7 years ago by the Food and Drug Administration in a Drug Safety Communication for accumulating reports of AKI linked to their use.

More recent experience has calmed AKI concerns, however.

Commenting on the new study, F. Perry Wilson, MD, a nephrologist at Yale University, New Haven, Conn., said: “It’s a nice piece of data to demonstrate that the long-term risk from SGLT2 inhibitor treatment is low.” Dr. Wilson was not involved with the new study.

The Taiwan study found a cumulative incidence of AKI events during about 2.5 years of follow-up of 5.55 events/1,000 patient-years among adults with type 2 diabetes receiving an SGLT2 inhibitor and 7.88 events/1,000 patient-years among those taking a DPP4 inhibitor such as sitagliptin (Januvia).

Main barrier to SGLT2 inhibitor use is unfamiliarity, not AKI risk

“My impression is that the main barrier to wider use of the SGLT2 inhibitor class is not a perceived risk for causing AKI, but rather ongoing unfamiliarity with the class,” Dr. Wilson said in an interview.

Although he sees “relatively broad comfort with and enthusiasm for the class among nephrologists and cardiologists,” routine prescribing does not seem to have caught on nearly as much among primary care physicians, he said.

Clinicians in primary care “still perceive the SGLT2 inhibitor class as something of a ‘specialty drug,’ and they defer initiating it on that basis,” Dr. Wilson observed. “That’s probably not a good thing,” as many people with type 2 diabetes do not have access to a specialized clinician who might be more amenable to prescribing an SGLT2 inhibitor.

One example of the lag in SGLT2 inhibitor uptake for people with type 2 diabetes in practice was a recent report from the Centers for Disease Control and Prevention published in Annals of Internal Medicine. Researchers identified a representative U.S. sample of 1,330 adults with type 2 diabetes studied in depth during 2017-2020, of whom 82% fulfilled criteria published in 2022 for receiving treatment with an SGLT2 inhibitor. Despite this high prevalence of medical appropriateness, a scant 5.3% of those with a recommended indication actually received an agent from this class.

Early AKI concern has diminished

Results from more recent studies, such as a 2019 meta-analysis of more than 100 randomized studies and four large observational studies that together included about 180,000 people receiving SGLT2 inhibitor treatment, showed the opposite of SGLT2 inhibitor treatment triggering AKI.

In the trials, people taking an SGLT2 inhibitor had a relative 25% lower rate of AKI events, while in the observational studies, SGLT2 inhibitor treatment was linked with a 60% relative reduction in AKI. The study also found that SGLT2 inhibitor use in the trials was linked with a significant 20% relative increase in the incidence of low fluid volume.

Despite accumulated evidence exonerating AKI risk, U.S. labels for canagliflozin, dapagliflozin, and empagliflozin continue to cite AKI as a potential adverse reaction, especially in patients who undergo volume depletion while on SGLT2 inhibitor treatment.

The new Taiwan study used data from the country’s National Health Insurance Research Database. Out of more than 250,000 adults with type 2 diabetes in the system from May 2016 to December 2018, the researchers identified 52,231 propensity-score matched pairs of people where one was on treatment with an SGLT2 inhibitor and the other with a DPP4 inhibitor.

During follow-up, 856 of these people (0.8%) had an AKI event, including 102 people with AKI that required dialysis.

A logistic regression analysis that adjusted for 16 potential confounders showed that SGLT2 inhibitor treatment linked with a significant 34% reduction in AKI events compared with DPP4 inhibitor treatment, as well as with a significant 44% relative risk reduction in the incidence of AKI events requiring dialysis, reported the authors from several medical institutions in Taiwan.

The study’s main limitation was its reliance on “quite insensitive” administrative coding data to identify AKI cases, said Dr. Wilson.

He noted that although concern about AKI events secondary to SGLT2 inhibitor treatment is uncommon among U.S. clinicians they do worry about the potential risk for fungal infections, urinary tract infection, or gangrene in people with diabetes who receive an agent from this class.

The study received no commercial funding, and none of the authors had disclosures. Dr. Wilson has reported receiving research funding from AstraZeneca, Boehringer Ingelheim, Vifor, and Whoop.

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

Adults with type 2 diabetes treated with an SGLT2 inhibitor had roughly a third fewer episodes of acute kidney injury (AKI) compared with matched people with type 2 diabetes treated with a DPP4 inhibitor, in an analysis of health insurance data from more than 100,000 Taiwan residents during 2016-2018.

The findings add to, and expand on, prior evidence that treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class cuts the incidence of AKI, say the authors of the report, which was recently published in JAMA Network Open.

The long-term risk for AKI among people with type 2 diabetes treated with an SGLT2 inhibitor “appears to be quite low” compared with adults who received an agent from the dipeptidyl peptidase 4 (DPP4) inhibitor class.

Treatment with an SGLT2 inhibitor – such as canagliflozin (Invokana), dapagliflozin (Farxiga), or empagliflozin (Jardiance) – causes a transient drop in kidney function that manifests as a temporary dip in estimated glomerular filtration rate, which caused concerns about AKI when the drugs were first introduced.

Indeed, canagliflozin and dapagliflozin had warnings strengthened 7 years ago by the Food and Drug Administration in a Drug Safety Communication for accumulating reports of AKI linked to their use.

More recent experience has calmed AKI concerns, however.

Commenting on the new study, F. Perry Wilson, MD, a nephrologist at Yale University, New Haven, Conn., said: “It’s a nice piece of data to demonstrate that the long-term risk from SGLT2 inhibitor treatment is low.” Dr. Wilson was not involved with the new study.

The Taiwan study found a cumulative incidence of AKI events during about 2.5 years of follow-up of 5.55 events/1,000 patient-years among adults with type 2 diabetes receiving an SGLT2 inhibitor and 7.88 events/1,000 patient-years among those taking a DPP4 inhibitor such as sitagliptin (Januvia).

Main barrier to SGLT2 inhibitor use is unfamiliarity, not AKI risk

“My impression is that the main barrier to wider use of the SGLT2 inhibitor class is not a perceived risk for causing AKI, but rather ongoing unfamiliarity with the class,” Dr. Wilson said in an interview.

Although he sees “relatively broad comfort with and enthusiasm for the class among nephrologists and cardiologists,” routine prescribing does not seem to have caught on nearly as much among primary care physicians, he said.

Clinicians in primary care “still perceive the SGLT2 inhibitor class as something of a ‘specialty drug,’ and they defer initiating it on that basis,” Dr. Wilson observed. “That’s probably not a good thing,” as many people with type 2 diabetes do not have access to a specialized clinician who might be more amenable to prescribing an SGLT2 inhibitor.

One example of the lag in SGLT2 inhibitor uptake for people with type 2 diabetes in practice was a recent report from the Centers for Disease Control and Prevention published in Annals of Internal Medicine. Researchers identified a representative U.S. sample of 1,330 adults with type 2 diabetes studied in depth during 2017-2020, of whom 82% fulfilled criteria published in 2022 for receiving treatment with an SGLT2 inhibitor. Despite this high prevalence of medical appropriateness, a scant 5.3% of those with a recommended indication actually received an agent from this class.

Early AKI concern has diminished

Results from more recent studies, such as a 2019 meta-analysis of more than 100 randomized studies and four large observational studies that together included about 180,000 people receiving SGLT2 inhibitor treatment, showed the opposite of SGLT2 inhibitor treatment triggering AKI.

In the trials, people taking an SGLT2 inhibitor had a relative 25% lower rate of AKI events, while in the observational studies, SGLT2 inhibitor treatment was linked with a 60% relative reduction in AKI. The study also found that SGLT2 inhibitor use in the trials was linked with a significant 20% relative increase in the incidence of low fluid volume.

Despite accumulated evidence exonerating AKI risk, U.S. labels for canagliflozin, dapagliflozin, and empagliflozin continue to cite AKI as a potential adverse reaction, especially in patients who undergo volume depletion while on SGLT2 inhibitor treatment.

The new Taiwan study used data from the country’s National Health Insurance Research Database. Out of more than 250,000 adults with type 2 diabetes in the system from May 2016 to December 2018, the researchers identified 52,231 propensity-score matched pairs of people where one was on treatment with an SGLT2 inhibitor and the other with a DPP4 inhibitor.

During follow-up, 856 of these people (0.8%) had an AKI event, including 102 people with AKI that required dialysis.

A logistic regression analysis that adjusted for 16 potential confounders showed that SGLT2 inhibitor treatment linked with a significant 34% reduction in AKI events compared with DPP4 inhibitor treatment, as well as with a significant 44% relative risk reduction in the incidence of AKI events requiring dialysis, reported the authors from several medical institutions in Taiwan.

The study’s main limitation was its reliance on “quite insensitive” administrative coding data to identify AKI cases, said Dr. Wilson.

He noted that although concern about AKI events secondary to SGLT2 inhibitor treatment is uncommon among U.S. clinicians they do worry about the potential risk for fungal infections, urinary tract infection, or gangrene in people with diabetes who receive an agent from this class.

The study received no commercial funding, and none of the authors had disclosures. Dr. Wilson has reported receiving research funding from AstraZeneca, Boehringer Ingelheim, Vifor, and Whoop.

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

Adults with type 2 diabetes treated with an SGLT2 inhibitor had roughly a third fewer episodes of acute kidney injury (AKI) compared with matched people with type 2 diabetes treated with a DPP4 inhibitor, in an analysis of health insurance data from more than 100,000 Taiwan residents during 2016-2018.

The findings add to, and expand on, prior evidence that treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class cuts the incidence of AKI, say the authors of the report, which was recently published in JAMA Network Open.

The long-term risk for AKI among people with type 2 diabetes treated with an SGLT2 inhibitor “appears to be quite low” compared with adults who received an agent from the dipeptidyl peptidase 4 (DPP4) inhibitor class.

Treatment with an SGLT2 inhibitor – such as canagliflozin (Invokana), dapagliflozin (Farxiga), or empagliflozin (Jardiance) – causes a transient drop in kidney function that manifests as a temporary dip in estimated glomerular filtration rate, which caused concerns about AKI when the drugs were first introduced.

Indeed, canagliflozin and dapagliflozin had warnings strengthened 7 years ago by the Food and Drug Administration in a Drug Safety Communication for accumulating reports of AKI linked to their use.

More recent experience has calmed AKI concerns, however.

Commenting on the new study, F. Perry Wilson, MD, a nephrologist at Yale University, New Haven, Conn., said: “It’s a nice piece of data to demonstrate that the long-term risk from SGLT2 inhibitor treatment is low.” Dr. Wilson was not involved with the new study.

The Taiwan study found a cumulative incidence of AKI events during about 2.5 years of follow-up of 5.55 events/1,000 patient-years among adults with type 2 diabetes receiving an SGLT2 inhibitor and 7.88 events/1,000 patient-years among those taking a DPP4 inhibitor such as sitagliptin (Januvia).

Main barrier to SGLT2 inhibitor use is unfamiliarity, not AKI risk

“My impression is that the main barrier to wider use of the SGLT2 inhibitor class is not a perceived risk for causing AKI, but rather ongoing unfamiliarity with the class,” Dr. Wilson said in an interview.

Although he sees “relatively broad comfort with and enthusiasm for the class among nephrologists and cardiologists,” routine prescribing does not seem to have caught on nearly as much among primary care physicians, he said.

Clinicians in primary care “still perceive the SGLT2 inhibitor class as something of a ‘specialty drug,’ and they defer initiating it on that basis,” Dr. Wilson observed. “That’s probably not a good thing,” as many people with type 2 diabetes do not have access to a specialized clinician who might be more amenable to prescribing an SGLT2 inhibitor.

One example of the lag in SGLT2 inhibitor uptake for people with type 2 diabetes in practice was a recent report from the Centers for Disease Control and Prevention published in Annals of Internal Medicine. Researchers identified a representative U.S. sample of 1,330 adults with type 2 diabetes studied in depth during 2017-2020, of whom 82% fulfilled criteria published in 2022 for receiving treatment with an SGLT2 inhibitor. Despite this high prevalence of medical appropriateness, a scant 5.3% of those with a recommended indication actually received an agent from this class.

Early AKI concern has diminished

Results from more recent studies, such as a 2019 meta-analysis of more than 100 randomized studies and four large observational studies that together included about 180,000 people receiving SGLT2 inhibitor treatment, showed the opposite of SGLT2 inhibitor treatment triggering AKI.

In the trials, people taking an SGLT2 inhibitor had a relative 25% lower rate of AKI events, while in the observational studies, SGLT2 inhibitor treatment was linked with a 60% relative reduction in AKI. The study also found that SGLT2 inhibitor use in the trials was linked with a significant 20% relative increase in the incidence of low fluid volume.

Despite accumulated evidence exonerating AKI risk, U.S. labels for canagliflozin, dapagliflozin, and empagliflozin continue to cite AKI as a potential adverse reaction, especially in patients who undergo volume depletion while on SGLT2 inhibitor treatment.

The new Taiwan study used data from the country’s National Health Insurance Research Database. Out of more than 250,000 adults with type 2 diabetes in the system from May 2016 to December 2018, the researchers identified 52,231 propensity-score matched pairs of people where one was on treatment with an SGLT2 inhibitor and the other with a DPP4 inhibitor.

During follow-up, 856 of these people (0.8%) had an AKI event, including 102 people with AKI that required dialysis.

A logistic regression analysis that adjusted for 16 potential confounders showed that SGLT2 inhibitor treatment linked with a significant 34% reduction in AKI events compared with DPP4 inhibitor treatment, as well as with a significant 44% relative risk reduction in the incidence of AKI events requiring dialysis, reported the authors from several medical institutions in Taiwan.

The study’s main limitation was its reliance on “quite insensitive” administrative coding data to identify AKI cases, said Dr. Wilson.

He noted that although concern about AKI events secondary to SGLT2 inhibitor treatment is uncommon among U.S. clinicians they do worry about the potential risk for fungal infections, urinary tract infection, or gangrene in people with diabetes who receive an agent from this class.

The study received no commercial funding, and none of the authors had disclosures. Dr. Wilson has reported receiving research funding from AstraZeneca, Boehringer Ingelheim, Vifor, and Whoop.

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

Metformin appears to play a role in preventing long COVID when taken early during a COVID-19 infection, according to preprints with The Lancet on SSRN. The preprint hasn’t yet been peer-reviewed or published in a journal.

In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection. 

“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” said lead author Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics at the University of Minnesota, Minneapolis.

Between January 2021 and February 2022, Dr. Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.

The researchers included patients who were aged 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.

The medications were prepackaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.

The metformin doses were doled out over 14 days, with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.

Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID: 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant. 

The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.

Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.

The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.

When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.

Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.

At the same time, the study authors caution that more research is needed. 

“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”

Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only 1 of the 57 people who received a booster shot developed long COVID.

Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most nonobstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.

The results are now under journal review but show findings consistent with those from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.

“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals. 

Dr. Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Dr. Topol also wrote about the preprint in Ground Truths, his online newsletter.

“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of its being so safe and low cost, I’d give it a breakthrough categorization.”

Another way to put it, Dr. Topol wrote, is that based on this study, he would take metformin if he became infected with COVID-19. 

Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”

“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”

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

Metformin appears to play a role in preventing long COVID when taken early during a COVID-19 infection, according to preprints with The Lancet on SSRN. The preprint hasn’t yet been peer-reviewed or published in a journal.

In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection. 

“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” said lead author Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics at the University of Minnesota, Minneapolis.

Between January 2021 and February 2022, Dr. Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.

The researchers included patients who were aged 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.

The medications were prepackaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.

The metformin doses were doled out over 14 days, with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.

Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID: 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant. 

The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.

Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.

The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.

When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.

Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.

At the same time, the study authors caution that more research is needed. 

“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”

Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only 1 of the 57 people who received a booster shot developed long COVID.

Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most nonobstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.

The results are now under journal review but show findings consistent with those from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.

“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals. 

Dr. Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Dr. Topol also wrote about the preprint in Ground Truths, his online newsletter.

“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of its being so safe and low cost, I’d give it a breakthrough categorization.”

Another way to put it, Dr. Topol wrote, is that based on this study, he would take metformin if he became infected with COVID-19. 

Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”

“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”

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

Metformin appears to play a role in preventing long COVID when taken early during a COVID-19 infection, according to preprints with The Lancet on SSRN. The preprint hasn’t yet been peer-reviewed or published in a journal.

In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection. 

“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” said lead author Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics at the University of Minnesota, Minneapolis.

Between January 2021 and February 2022, Dr. Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.

The researchers included patients who were aged 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.

The medications were prepackaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.

The metformin doses were doled out over 14 days, with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.

Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID: 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant. 

The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.

Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.

The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.

When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.

Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.

At the same time, the study authors caution that more research is needed. 

“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”

Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only 1 of the 57 people who received a booster shot developed long COVID.

Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most nonobstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.

The results are now under journal review but show findings consistent with those from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.

“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals. 

Dr. Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Dr. Topol also wrote about the preprint in Ground Truths, his online newsletter.

“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of its being so safe and low cost, I’d give it a breakthrough categorization.”

Another way to put it, Dr. Topol wrote, is that based on this study, he would take metformin if he became infected with COVID-19. 

Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”

“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”

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

Children who experience migraine headaches in the aftermath of a concussion are more likely to experience prolonged symptoms of the head injury than are those with other forms of headache or no headaches at all, researchers have found.

“Early assessment of headache – and whether it has migraine features – after concussion can be helpful in predicting which children are at risk for poor outcomes and identifying children who require targeted intervention,” said senior author Keith Owen Yeates, PhD, the Ronald and Irene Ward Chair in Pediatric Brain Injury Professor and head of the department of psychology at the University of Calgary (Alta.). “Posttraumatic headache, especially when it involves migraine features, is a strong predictor of persisting symptoms and poorer quality of life after childhood concussion.”

Approximately 840,000 children per year visit an emergency department in the United States after having a traumatic brain injury. As many as 90% of those visits are considered to involve a concussion, according to the investigators. Although most children recover quickly, approximately one-third continue to report symptoms a month after the event.

Posttraumatic headache occurs in up to 90% of children, most commonly with features of migraine.

The new study, published in JAMA Network Open, was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study. The study was conducted at five emergency departments in Canada from September 2016 to July 2019 and included children and adolescents aged 8-17 years who presented with acute concussion or an orthopedic injury.

Children were included in the concussion group if they had a history of blunt head trauma resulting in at least one of three criteria consistent with the World Health Organization definition of mild traumatic brain injury. The criteria include loss of consciousness for less than 30 minutes, a Glasgow Coma Scale score of 13 or 14, or at least one acute sign or symptom of concussion, as noted by emergency clinicians.

Patients were excluded from the concussion group if they had deteriorating neurologic status, underwent neurosurgical intervention, had posttraumatic amnesia that lasted more than 24 hours, or had a score higher than 4 on the Abbreviated Injury Scale (AIS). The orthopedic injury group included patients without symptoms of concussion and with blunt trauma associated with an AIS 13 score of 4 or less. Patients were excluded from both groups if they had an overnight hospitalization for traumatic brain injury, a concussion within the past 3 months, or a neurodevelopmental disorder.

The researchers analyzed data from 928 children of 967 enrolled in the study. The median age was 12.2 years, and 41.3% were female. The final study cohort included 239 children with orthopedic injuries but no headache, 160 with a concussion and no headache, 134 with a concussion and nonmigraine headaches, and 254 with a concussion and migraine headaches.

Children with posttraumatic migraines 10 days after a concussion had the most severe symptoms and worst quality of life 3 months following their head trauma, the researchers found. Children without headaches within 10 days after concussion had the best 3-month outcomes, comparable to those with orthopedic injuries alone.

The researchers said the strengths of their study included its large population and its inclusion of various causes of head trauma, not just sports-related concussions. Limitations included self-reports of headaches instead of a physician diagnosis and lack of control for clinical interventions that might have affected the outcomes.

Charles Tator, MD, PhD, director of the Canadian Concussion Centre at Toronto Western Hospital, said the findings were unsurprising.

“Headaches are the most common symptom after concussion,” Dr. Tator, who was not involved in the latest research, told this news organization. “In my practice and research with concussed kids 11 and up and with adults, those with preconcussion history of migraine are the most difficult to treat because their headaches don’t improve unless specific measures are taken.”

Dr. Tator, who also is a professor of neurosurgery at the University of Toronto, said clinicians who treat concussions must determine which type of headaches children are experiencing – and refer as early as possible for migraine prevention or treatment and medication, as warranted.

“Early recognition after concussion that migraine headaches are occurring will save kids a lot of suffering,” he said.

The study was supported by a Canadian Institute of Health Research Foundation Grant and by funds from the Alberta Children’s Hospital Foundation and the Alberta Children’s Hospital Research Institute. Dr. Tator has disclosed no relevant financial relationships.
 

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

Children who experience migraine headaches in the aftermath of a concussion are more likely to experience prolonged symptoms of the head injury than are those with other forms of headache or no headaches at all, researchers have found.

“Early assessment of headache – and whether it has migraine features – after concussion can be helpful in predicting which children are at risk for poor outcomes and identifying children who require targeted intervention,” said senior author Keith Owen Yeates, PhD, the Ronald and Irene Ward Chair in Pediatric Brain Injury Professor and head of the department of psychology at the University of Calgary (Alta.). “Posttraumatic headache, especially when it involves migraine features, is a strong predictor of persisting symptoms and poorer quality of life after childhood concussion.”

Approximately 840,000 children per year visit an emergency department in the United States after having a traumatic brain injury. As many as 90% of those visits are considered to involve a concussion, according to the investigators. Although most children recover quickly, approximately one-third continue to report symptoms a month after the event.

Posttraumatic headache occurs in up to 90% of children, most commonly with features of migraine.

The new study, published in JAMA Network Open, was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study. The study was conducted at five emergency departments in Canada from September 2016 to July 2019 and included children and adolescents aged 8-17 years who presented with acute concussion or an orthopedic injury.

Children were included in the concussion group if they had a history of blunt head trauma resulting in at least one of three criteria consistent with the World Health Organization definition of mild traumatic brain injury. The criteria include loss of consciousness for less than 30 minutes, a Glasgow Coma Scale score of 13 or 14, or at least one acute sign or symptom of concussion, as noted by emergency clinicians.

Patients were excluded from the concussion group if they had deteriorating neurologic status, underwent neurosurgical intervention, had posttraumatic amnesia that lasted more than 24 hours, or had a score higher than 4 on the Abbreviated Injury Scale (AIS). The orthopedic injury group included patients without symptoms of concussion and with blunt trauma associated with an AIS 13 score of 4 or less. Patients were excluded from both groups if they had an overnight hospitalization for traumatic brain injury, a concussion within the past 3 months, or a neurodevelopmental disorder.

The researchers analyzed data from 928 children of 967 enrolled in the study. The median age was 12.2 years, and 41.3% were female. The final study cohort included 239 children with orthopedic injuries but no headache, 160 with a concussion and no headache, 134 with a concussion and nonmigraine headaches, and 254 with a concussion and migraine headaches.

Children with posttraumatic migraines 10 days after a concussion had the most severe symptoms and worst quality of life 3 months following their head trauma, the researchers found. Children without headaches within 10 days after concussion had the best 3-month outcomes, comparable to those with orthopedic injuries alone.

The researchers said the strengths of their study included its large population and its inclusion of various causes of head trauma, not just sports-related concussions. Limitations included self-reports of headaches instead of a physician diagnosis and lack of control for clinical interventions that might have affected the outcomes.

Charles Tator, MD, PhD, director of the Canadian Concussion Centre at Toronto Western Hospital, said the findings were unsurprising.

“Headaches are the most common symptom after concussion,” Dr. Tator, who was not involved in the latest research, told this news organization. “In my practice and research with concussed kids 11 and up and with adults, those with preconcussion history of migraine are the most difficult to treat because their headaches don’t improve unless specific measures are taken.”

Dr. Tator, who also is a professor of neurosurgery at the University of Toronto, said clinicians who treat concussions must determine which type of headaches children are experiencing – and refer as early as possible for migraine prevention or treatment and medication, as warranted.

“Early recognition after concussion that migraine headaches are occurring will save kids a lot of suffering,” he said.

The study was supported by a Canadian Institute of Health Research Foundation Grant and by funds from the Alberta Children’s Hospital Foundation and the Alberta Children’s Hospital Research Institute. Dr. Tator has disclosed no relevant financial relationships.
 

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

Children who experience migraine headaches in the aftermath of a concussion are more likely to experience prolonged symptoms of the head injury than are those with other forms of headache or no headaches at all, researchers have found.

“Early assessment of headache – and whether it has migraine features – after concussion can be helpful in predicting which children are at risk for poor outcomes and identifying children who require targeted intervention,” said senior author Keith Owen Yeates, PhD, the Ronald and Irene Ward Chair in Pediatric Brain Injury Professor and head of the department of psychology at the University of Calgary (Alta.). “Posttraumatic headache, especially when it involves migraine features, is a strong predictor of persisting symptoms and poorer quality of life after childhood concussion.”

Approximately 840,000 children per year visit an emergency department in the United States after having a traumatic brain injury. As many as 90% of those visits are considered to involve a concussion, according to the investigators. Although most children recover quickly, approximately one-third continue to report symptoms a month after the event.

Posttraumatic headache occurs in up to 90% of children, most commonly with features of migraine.

The new study, published in JAMA Network Open, was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study. The study was conducted at five emergency departments in Canada from September 2016 to July 2019 and included children and adolescents aged 8-17 years who presented with acute concussion or an orthopedic injury.

Children were included in the concussion group if they had a history of blunt head trauma resulting in at least one of three criteria consistent with the World Health Organization definition of mild traumatic brain injury. The criteria include loss of consciousness for less than 30 minutes, a Glasgow Coma Scale score of 13 or 14, or at least one acute sign or symptom of concussion, as noted by emergency clinicians.

Patients were excluded from the concussion group if they had deteriorating neurologic status, underwent neurosurgical intervention, had posttraumatic amnesia that lasted more than 24 hours, or had a score higher than 4 on the Abbreviated Injury Scale (AIS). The orthopedic injury group included patients without symptoms of concussion and with blunt trauma associated with an AIS 13 score of 4 or less. Patients were excluded from both groups if they had an overnight hospitalization for traumatic brain injury, a concussion within the past 3 months, or a neurodevelopmental disorder.

The researchers analyzed data from 928 children of 967 enrolled in the study. The median age was 12.2 years, and 41.3% were female. The final study cohort included 239 children with orthopedic injuries but no headache, 160 with a concussion and no headache, 134 with a concussion and nonmigraine headaches, and 254 with a concussion and migraine headaches.

Children with posttraumatic migraines 10 days after a concussion had the most severe symptoms and worst quality of life 3 months following their head trauma, the researchers found. Children without headaches within 10 days after concussion had the best 3-month outcomes, comparable to those with orthopedic injuries alone.

The researchers said the strengths of their study included its large population and its inclusion of various causes of head trauma, not just sports-related concussions. Limitations included self-reports of headaches instead of a physician diagnosis and lack of control for clinical interventions that might have affected the outcomes.

Charles Tator, MD, PhD, director of the Canadian Concussion Centre at Toronto Western Hospital, said the findings were unsurprising.

“Headaches are the most common symptom after concussion,” Dr. Tator, who was not involved in the latest research, told this news organization. “In my practice and research with concussed kids 11 and up and with adults, those with preconcussion history of migraine are the most difficult to treat because their headaches don’t improve unless specific measures are taken.”

Dr. Tator, who also is a professor of neurosurgery at the University of Toronto, said clinicians who treat concussions must determine which type of headaches children are experiencing – and refer as early as possible for migraine prevention or treatment and medication, as warranted.

“Early recognition after concussion that migraine headaches are occurring will save kids a lot of suffering,” he said.

The study was supported by a Canadian Institute of Health Research Foundation Grant and by funds from the Alberta Children’s Hospital Foundation and the Alberta Children’s Hospital Research Institute. Dr. Tator has disclosed no relevant financial relationships.
 

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

Childhood obesity is a risk factor for four of the five subtypes of adult-onset diabetes, emphasizing the importance of childhood weight control, according to a collaborative study from the Karolinska Institutet in Stockholm, the University of Bristol (England), and Sun Yat-Sen University in China.

“Our finding is that children who have a bigger body size than the average have increased risks of developing almost all subtypes of adult-onset diabetes, except for the mild age-related subtype,” lead author Yuxia Wei, a PhD student from the Karolinska Institutet, said in an interview. “This tells us that it is important to prevent overweight/obesity in children and important for pediatric patients to lose weight if they have already been overweight/obese,” she added, while acknowledging that the study did not examine whether childhood weight loss would prevent adult-onset diabetes.

The study, published online in Diabetologia, used Mendelian randomization (MR), with data from genome-wide association studies (GWAS) of childhood obesity and the five subtypes of adult-onset diabetes: latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). MR is “a rather new but commonly used and established technique that uses genetic information to study the causal link between an environmental risk factor and a disease, while accounting for the influence of other risk factors,” Ms. Wei explained.

To identify genetic variations associated with obesity, the study used statistics from a GWAS of 453,169 Europeans who self-reported body size at age 10 years in the UK Biobank study. After adjustment for sex, age at baseline, type of genotyping array, and month of birth, they identified 295 independent single nucleotide polymorphisms (SNPs) for childhood body size.

The researchers also used data from two GWAS of European adults with newly diagnosed diabetes, or without diabetes, to identify SNPs in 8,581 individuals with LADA, 3,937 with SIDD, 3,874 with SIRD, 4,118 with MOD, and 5,605 with MARD.

They then used MR to assess the association of genetically predicted childhood body size with the different diabetes subtypes.

The analysis showed that, with the exception of MARD, all other adult-onset diabetes subtypes were causally associated with childhood obesity, with odds ratio of 1.62 for LADA, 2.11 for SIDD, 2.76 for SIRD, and 7.30 for MOD. However, a genetic correlation between childhood obesity and adult-onset diabetes was found only for MOD, and no other subtypes. “The weak genetic correlation between childhood obesity and adult diabetes indicates that the genes promoting childhood adiposity are largely distinct from those promoting diabetes during adulthood,” noted the authors.

The findings indicate that “childhood body size and MOD may share some genetic mutations,” added Ms. Wei. “That is to say, some genes may affect childhood body size and MOD simultaneously.” But the shared genes do demonstrate the causal effect of childhood obesity on MOD, she explained. The causal effect is demonstrated through the MR analysis.

Additionally, they noted that while “the link between childhood body size and SIRD is expected, given the adverse effects of adiposity on insulin sensitivity ... the smaller OR for SIRD than for MOD suggests that non–obesity-related and/or nongenetic effects may be the main factors underlying the development of SIRD.” Asked for her theory on how childhood body size could affect diabetes subtypes characterized by autoimmunity (LADA) or impaired insulin secretion (SIDD), Ms. Wei speculated that “excess fat around the pancreas can affect insulin secretion and that impaired insulin secretion is also an important problem for LADA.”

Another theory is that it might be “metabolic memory,” suggested Jordi Merino, PhD, of the University of Copenhagen and Harvard University, Boston, who was not involved in the research. “Being exposed to obesity during childhood will tell the body to produce more insulin/aberrant immunity responses later in life.”

Dr. Merino said that, overall, the study’s findings “highlight the long and lasting effect of early-life adiposity and metabolic alterations on different forms of adult-onset diabetes,” adding that this is the first evidence “that childhood adiposity is not only linked to the more traditional diabetes subtype consequence of increased insulin resistance but also subtypes driven by autoimmunity or impaired insulin secretion.” He explained that genetics is “only part of the story” driving increased diabetes risk and “we do not know much about other factors interacting with genetics, but the results from this Mendelian randomization analysis suggest that childhood obesity is a causal factor for all adult-onset diabetes subtypes. Identifying causal factors instead of associative factors is critical to implement more targeted preventive and therapeutic strategies.”

He acknowledged, “There is a long path for these results to be eventually implemented in clinical practice, but they can support early weight control strategies for preventing different diabetes subtypes.”

The study was supported by the Swedish Research Council, Research Council for Health, Working Life and Welfare, and Novo Nordisk Foundation. Ms. Wei received a scholarship from the China Scholarship Council. One coauthor is an employee of GlaxoSmithKline. Dr. Merino reported no conflicts of interest.

Childhood obesity is a risk factor for four of the five subtypes of adult-onset diabetes, emphasizing the importance of childhood weight control, according to a collaborative study from the Karolinska Institutet in Stockholm, the University of Bristol (England), and Sun Yat-Sen University in China.

“Our finding is that children who have a bigger body size than the average have increased risks of developing almost all subtypes of adult-onset diabetes, except for the mild age-related subtype,” lead author Yuxia Wei, a PhD student from the Karolinska Institutet, said in an interview. “This tells us that it is important to prevent overweight/obesity in children and important for pediatric patients to lose weight if they have already been overweight/obese,” she added, while acknowledging that the study did not examine whether childhood weight loss would prevent adult-onset diabetes.

The study, published online in Diabetologia, used Mendelian randomization (MR), with data from genome-wide association studies (GWAS) of childhood obesity and the five subtypes of adult-onset diabetes: latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). MR is “a rather new but commonly used and established technique that uses genetic information to study the causal link between an environmental risk factor and a disease, while accounting for the influence of other risk factors,” Ms. Wei explained.

To identify genetic variations associated with obesity, the study used statistics from a GWAS of 453,169 Europeans who self-reported body size at age 10 years in the UK Biobank study. After adjustment for sex, age at baseline, type of genotyping array, and month of birth, they identified 295 independent single nucleotide polymorphisms (SNPs) for childhood body size.

The researchers also used data from two GWAS of European adults with newly diagnosed diabetes, or without diabetes, to identify SNPs in 8,581 individuals with LADA, 3,937 with SIDD, 3,874 with SIRD, 4,118 with MOD, and 5,605 with MARD.

They then used MR to assess the association of genetically predicted childhood body size with the different diabetes subtypes.

The analysis showed that, with the exception of MARD, all other adult-onset diabetes subtypes were causally associated with childhood obesity, with odds ratio of 1.62 for LADA, 2.11 for SIDD, 2.76 for SIRD, and 7.30 for MOD. However, a genetic correlation between childhood obesity and adult-onset diabetes was found only for MOD, and no other subtypes. “The weak genetic correlation between childhood obesity and adult diabetes indicates that the genes promoting childhood adiposity are largely distinct from those promoting diabetes during adulthood,” noted the authors.

The findings indicate that “childhood body size and MOD may share some genetic mutations,” added Ms. Wei. “That is to say, some genes may affect childhood body size and MOD simultaneously.” But the shared genes do demonstrate the causal effect of childhood obesity on MOD, she explained. The causal effect is demonstrated through the MR analysis.

Additionally, they noted that while “the link between childhood body size and SIRD is expected, given the adverse effects of adiposity on insulin sensitivity ... the smaller OR for SIRD than for MOD suggests that non–obesity-related and/or nongenetic effects may be the main factors underlying the development of SIRD.” Asked for her theory on how childhood body size could affect diabetes subtypes characterized by autoimmunity (LADA) or impaired insulin secretion (SIDD), Ms. Wei speculated that “excess fat around the pancreas can affect insulin secretion and that impaired insulin secretion is also an important problem for LADA.”

Another theory is that it might be “metabolic memory,” suggested Jordi Merino, PhD, of the University of Copenhagen and Harvard University, Boston, who was not involved in the research. “Being exposed to obesity during childhood will tell the body to produce more insulin/aberrant immunity responses later in life.”

Dr. Merino said that, overall, the study’s findings “highlight the long and lasting effect of early-life adiposity and metabolic alterations on different forms of adult-onset diabetes,” adding that this is the first evidence “that childhood adiposity is not only linked to the more traditional diabetes subtype consequence of increased insulin resistance but also subtypes driven by autoimmunity or impaired insulin secretion.” He explained that genetics is “only part of the story” driving increased diabetes risk and “we do not know much about other factors interacting with genetics, but the results from this Mendelian randomization analysis suggest that childhood obesity is a causal factor for all adult-onset diabetes subtypes. Identifying causal factors instead of associative factors is critical to implement more targeted preventive and therapeutic strategies.”

He acknowledged, “There is a long path for these results to be eventually implemented in clinical practice, but they can support early weight control strategies for preventing different diabetes subtypes.”

The study was supported by the Swedish Research Council, Research Council for Health, Working Life and Welfare, and Novo Nordisk Foundation. Ms. Wei received a scholarship from the China Scholarship Council. One coauthor is an employee of GlaxoSmithKline. Dr. Merino reported no conflicts of interest.

Childhood obesity is a risk factor for four of the five subtypes of adult-onset diabetes, emphasizing the importance of childhood weight control, according to a collaborative study from the Karolinska Institutet in Stockholm, the University of Bristol (England), and Sun Yat-Sen University in China.

“Our finding is that children who have a bigger body size than the average have increased risks of developing almost all subtypes of adult-onset diabetes, except for the mild age-related subtype,” lead author Yuxia Wei, a PhD student from the Karolinska Institutet, said in an interview. “This tells us that it is important to prevent overweight/obesity in children and important for pediatric patients to lose weight if they have already been overweight/obese,” she added, while acknowledging that the study did not examine whether childhood weight loss would prevent adult-onset diabetes.

The study, published online in Diabetologia, used Mendelian randomization (MR), with data from genome-wide association studies (GWAS) of childhood obesity and the five subtypes of adult-onset diabetes: latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). MR is “a rather new but commonly used and established technique that uses genetic information to study the causal link between an environmental risk factor and a disease, while accounting for the influence of other risk factors,” Ms. Wei explained.

To identify genetic variations associated with obesity, the study used statistics from a GWAS of 453,169 Europeans who self-reported body size at age 10 years in the UK Biobank study. After adjustment for sex, age at baseline, type of genotyping array, and month of birth, they identified 295 independent single nucleotide polymorphisms (SNPs) for childhood body size.

The researchers also used data from two GWAS of European adults with newly diagnosed diabetes, or without diabetes, to identify SNPs in 8,581 individuals with LADA, 3,937 with SIDD, 3,874 with SIRD, 4,118 with MOD, and 5,605 with MARD.

They then used MR to assess the association of genetically predicted childhood body size with the different diabetes subtypes.

The analysis showed that, with the exception of MARD, all other adult-onset diabetes subtypes were causally associated with childhood obesity, with odds ratio of 1.62 for LADA, 2.11 for SIDD, 2.76 for SIRD, and 7.30 for MOD. However, a genetic correlation between childhood obesity and adult-onset diabetes was found only for MOD, and no other subtypes. “The weak genetic correlation between childhood obesity and adult diabetes indicates that the genes promoting childhood adiposity are largely distinct from those promoting diabetes during adulthood,” noted the authors.

The findings indicate that “childhood body size and MOD may share some genetic mutations,” added Ms. Wei. “That is to say, some genes may affect childhood body size and MOD simultaneously.” But the shared genes do demonstrate the causal effect of childhood obesity on MOD, she explained. The causal effect is demonstrated through the MR analysis.

Additionally, they noted that while “the link between childhood body size and SIRD is expected, given the adverse effects of adiposity on insulin sensitivity ... the smaller OR for SIRD than for MOD suggests that non–obesity-related and/or nongenetic effects may be the main factors underlying the development of SIRD.” Asked for her theory on how childhood body size could affect diabetes subtypes characterized by autoimmunity (LADA) or impaired insulin secretion (SIDD), Ms. Wei speculated that “excess fat around the pancreas can affect insulin secretion and that impaired insulin secretion is also an important problem for LADA.”

Another theory is that it might be “metabolic memory,” suggested Jordi Merino, PhD, of the University of Copenhagen and Harvard University, Boston, who was not involved in the research. “Being exposed to obesity during childhood will tell the body to produce more insulin/aberrant immunity responses later in life.”

Dr. Merino said that, overall, the study’s findings “highlight the long and lasting effect of early-life adiposity and metabolic alterations on different forms of adult-onset diabetes,” adding that this is the first evidence “that childhood adiposity is not only linked to the more traditional diabetes subtype consequence of increased insulin resistance but also subtypes driven by autoimmunity or impaired insulin secretion.” He explained that genetics is “only part of the story” driving increased diabetes risk and “we do not know much about other factors interacting with genetics, but the results from this Mendelian randomization analysis suggest that childhood obesity is a causal factor for all adult-onset diabetes subtypes. Identifying causal factors instead of associative factors is critical to implement more targeted preventive and therapeutic strategies.”

He acknowledged, “There is a long path for these results to be eventually implemented in clinical practice, but they can support early weight control strategies for preventing different diabetes subtypes.”

The study was supported by the Swedish Research Council, Research Council for Health, Working Life and Welfare, and Novo Nordisk Foundation. Ms. Wei received a scholarship from the China Scholarship Council. One coauthor is an employee of GlaxoSmithKline. Dr. Merino reported no conflicts of interest.

Two diabetes management devices that aid in the precision of insulin delivery have been recently cleared by the Food and Drug Administration.

On March 2, the FDA cleared the Android version of Bigfoot Biomedical’s Unity Mobile App for use with its system of smart pen caps that are compatible with different disposable insulin pens for administering both long-acting and rapid-acting insulin.

The system, which has been compatible with iOS devices since May 2021, is “the first and only FDA-cleared smart injection system that turns CGM [continuous glucose monitoring] data into dosing recommendations displayed right on the pen cap for people using multiple daily [insulin] injection therapy,” according to a company statement.

The Bigfoot app allows users to input and review provider treatment recommendations, displays current glucose ranges, and delivers real-time alerts.

Once it is commercially launched, the Android phone application will be available via the Google Play Store. “Given that 41% of U.S. smartphone users choose Android devices, this clearance enables expanded access to a large group of people with diabetes,” the company said.

On March 6, the FDA cleared the Abbott FreeStyle Libre 2 and FreeStyle Libre 3 devices as “integrated” CGM sensors. This means that they can now be used as components in automated insulin delivery systems, along with insulin pumps and connectivity software.

Abbott is working with insulin pump manufacturers Insulet and Tandem in the United States for integration with the FreeStyle Libre versions 2 and 3. Outside the United States, the Libre 3 is already authorized to work with mylife Loop from Ypsomed and CamDiab in Germany. Further launches are expected in the United Kingdom, Switzerland, and the Netherlands later this year.

The modified FreeStyle Libre 2 and FreeStyle Libre 3 sensors have been cleared for use by patients as young as age 2 years and for up to 15 days, in contrast to the previous versions, which were available for patients as young as 4 years for use up to 14 days. The FDA has cleared all Libre sensors – 2 and 3, current and future versions – for use by pregnant women with any type of diabetes.

The modified sensors will be available in the United States later this year and will eventually replace the Libre sensors in current use, the company said in a statement.

“The FreeStyle Libre portfolio is still the most affordable CGM on the market,” an Abbott representative said in an interview.

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

Two diabetes management devices that aid in the precision of insulin delivery have been recently cleared by the Food and Drug Administration.

On March 2, the FDA cleared the Android version of Bigfoot Biomedical’s Unity Mobile App for use with its system of smart pen caps that are compatible with different disposable insulin pens for administering both long-acting and rapid-acting insulin.

The system, which has been compatible with iOS devices since May 2021, is “the first and only FDA-cleared smart injection system that turns CGM [continuous glucose monitoring] data into dosing recommendations displayed right on the pen cap for people using multiple daily [insulin] injection therapy,” according to a company statement.

The Bigfoot app allows users to input and review provider treatment recommendations, displays current glucose ranges, and delivers real-time alerts.

Once it is commercially launched, the Android phone application will be available via the Google Play Store. “Given that 41% of U.S. smartphone users choose Android devices, this clearance enables expanded access to a large group of people with diabetes,” the company said.

On March 6, the FDA cleared the Abbott FreeStyle Libre 2 and FreeStyle Libre 3 devices as “integrated” CGM sensors. This means that they can now be used as components in automated insulin delivery systems, along with insulin pumps and connectivity software.

Abbott is working with insulin pump manufacturers Insulet and Tandem in the United States for integration with the FreeStyle Libre versions 2 and 3. Outside the United States, the Libre 3 is already authorized to work with mylife Loop from Ypsomed and CamDiab in Germany. Further launches are expected in the United Kingdom, Switzerland, and the Netherlands later this year.

The modified FreeStyle Libre 2 and FreeStyle Libre 3 sensors have been cleared for use by patients as young as age 2 years and for up to 15 days, in contrast to the previous versions, which were available for patients as young as 4 years for use up to 14 days. The FDA has cleared all Libre sensors – 2 and 3, current and future versions – for use by pregnant women with any type of diabetes.

The modified sensors will be available in the United States later this year and will eventually replace the Libre sensors in current use, the company said in a statement.

“The FreeStyle Libre portfolio is still the most affordable CGM on the market,” an Abbott representative said in an interview.

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

Two diabetes management devices that aid in the precision of insulin delivery have been recently cleared by the Food and Drug Administration.

On March 2, the FDA cleared the Android version of Bigfoot Biomedical’s Unity Mobile App for use with its system of smart pen caps that are compatible with different disposable insulin pens for administering both long-acting and rapid-acting insulin.

The system, which has been compatible with iOS devices since May 2021, is “the first and only FDA-cleared smart injection system that turns CGM [continuous glucose monitoring] data into dosing recommendations displayed right on the pen cap for people using multiple daily [insulin] injection therapy,” according to a company statement.

The Bigfoot app allows users to input and review provider treatment recommendations, displays current glucose ranges, and delivers real-time alerts.

Once it is commercially launched, the Android phone application will be available via the Google Play Store. “Given that 41% of U.S. smartphone users choose Android devices, this clearance enables expanded access to a large group of people with diabetes,” the company said.

On March 6, the FDA cleared the Abbott FreeStyle Libre 2 and FreeStyle Libre 3 devices as “integrated” CGM sensors. This means that they can now be used as components in automated insulin delivery systems, along with insulin pumps and connectivity software.

Abbott is working with insulin pump manufacturers Insulet and Tandem in the United States for integration with the FreeStyle Libre versions 2 and 3. Outside the United States, the Libre 3 is already authorized to work with mylife Loop from Ypsomed and CamDiab in Germany. Further launches are expected in the United Kingdom, Switzerland, and the Netherlands later this year.

The modified FreeStyle Libre 2 and FreeStyle Libre 3 sensors have been cleared for use by patients as young as age 2 years and for up to 15 days, in contrast to the previous versions, which were available for patients as young as 4 years for use up to 14 days. The FDA has cleared all Libre sensors – 2 and 3, current and future versions – for use by pregnant women with any type of diabetes.

The modified sensors will be available in the United States later this year and will eventually replace the Libre sensors in current use, the company said in a statement.

“The FreeStyle Libre portfolio is still the most affordable CGM on the market,” an Abbott representative said in an interview.

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

Adults who follow a heart-healthy lifestyle are more likely to live longer and to be free of chronic health conditions, based on data from a pair of related studies from the United States and United Kingdom involving nearly 200,000 individuals.

FatCamera/Getty Images

The studies, presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting in Boston, assessed the impact of cardiovascular health on life expectancy and freedom from chronic diseases. Cardiovascular health (CVH) was based on the Life’s Essential 8 (LE8) score, a composite of health metrics released by the American Heart Association in 2022. The LE8 was developed to guide research and assessment of cardiovascular health, and includes diet, physical activity, tobacco/nicotine exposure, sleep, body mass index, non-HDL cholesterol, blood glucose, and blood pressure.

In one study, Xuan Wang, MD, a postdoctoral fellow and biostatistician in the department of epidemiology at Tulane University, New Orleans, and colleagues reviewed data from 136,599 adults in the United Kingdom Biobank who were free of cardiovascular disease, diabetes, cancer, and dementia at baseline, and for whom complete LE8 data were available.

CVH was classified as poor, intermediate, and ideal, defined as LE8 scores of less than 50, 50 to 80, and 80 or higher, respectively.

The goal of the study was to examine the role of CVH based on LE8 scores on the percentage of life expectancy free of chronic diseases.

Men and women with ideal CVH averaged 5.2 years and 6.3 years more of total life expectancy at age 50 years, compared with those with poor CVH. Out of total life expectancy, the percentage of life expectancy free of chronic diseases was 75.9% and 83.4% for men and women, respectively, compared with 64.9% and 69.4%, respectively, for men and women with poor CVH.

The researchers also found that disparities in the percentage of disease-free years for both men and women were reduced in the high CVH groups.

The findings were limited by several factors including the use of only CVD, diabetes, cancer, and dementia in the definition of “disease-free life expectancy,” the researchers noted in a press release accompanying the study. Other limitations include the lack of data on e-cigarettes, and the homogeneous White study population. More research is needed in diverse populations who experience a stronger impact from negative social determinants of health, they said.

In a second study, Hao Ma, MD, and colleagues reviewed data from 23,003 adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 with mortality linked to the National Death Index through Dec. 31, 2019. The goal of the second study was to examine the association between CVH based on LE8 scores and life expectancy.

Over a median follow-up of 7.8 years, deaths occurred in 772 men and 587 women, said Dr. Ma, a postdoctoral fellow and biostatistician in epidemiology at Tulane University and coauthor on Dr. Wang’s study.

The estimated life expectancies at age 50 years for men with poor, intermediate, and ideal cardiovascular health based on the LE8 were 25.5 years, 31.2 years, and 33.1 years, respectively.

For women, the corresponding life expectancies for women at age 50 with poor, intermediate, and ideal CVH were 29.5 years, 34.2 years, and 38.4 years, respectively.

Men and women had similar gains in life expectancy from adhering to a heart-healthy lifestyle as defined by the LE8 score that reduced their risk of death from cardiovascular disease (41.8% and 44.1%, respectively).

Associations of cardiovascular health and life expectancy were similar for non-Hispanic Whites and non-Hispanic Blacks, but not among people of Mexican heritage, and more research is needed in diverse populations, the researchers wrote.

The study was limited by several factors including potential changes in cardiovascular health during the follow-up period, and by the limited analysis of racial and ethnic groups to non-Hispanic white, non-Hispanic Black, and people of Mexican heritage because of small sample sizes for other racial/ethnic groups, the researchers noted in a press release accompanying the study.

The message for clinicians and their patients is that adherence to cardiovascular health as defined by the LE8 will help not only extend life, but enhance quality of life, Dr. Xang and Dr. Ma said in an interview. “If your overall CVH score is low, we might be able to focus on one element first and improve them one by one,” they said. Sedentary lifestyle and an unhealthy diet are barriers to improving LE8 metrics that can be addressed, they added.

More research is needed to examine the effects of LE8 on high-risk patients, the researchers told this news organization. “No studies have yet focused on these patients with chronic diseases. We suspect that LE8 will play a role even in these high-risk groups,” they said. Further studies should include diverse populations and evaluations of the association between CVH change and health outcomes, they added.

“Overall, we see this 7.5-year difference [in life expectancy] going from poor to high cardiovascular health,” said Donald M. Lloyd-Jones, MD, of Northwestern University, Chicago, in a video accompanying the presentation of the study findings. The impact on life expectancy is yet another reason to motivate people to improve their cardiovascular health, said Dr. Lloyd-Jones, immediate past president of the American Heart Association and lead author on the writing group for Life’s Essential 8. “The earlier we do this, the better, and the greater the gains in life expectancy we’re likely to see in the U.S. population,” he said.

People maintaining high cardiovascular health into midlife are avoiding not only cardiovascular disease, but other chronic diseases of aging, Dr. Lloyd-Jones added. These conditions are delayed until much later in the lifespan, which allows people to enjoy better quality of life for more of their remaining years, he said.

The meeting was sponsored by the American Heart Association.

Both studies were supported by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health; the Fogarty International Center; and the Tulane Research Centers of Excellence Awards. The researchers had no financial conflicts to disclose.
 

Adults who follow a heart-healthy lifestyle are more likely to live longer and to be free of chronic health conditions, based on data from a pair of related studies from the United States and United Kingdom involving nearly 200,000 individuals.

FatCamera/Getty Images

The studies, presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting in Boston, assessed the impact of cardiovascular health on life expectancy and freedom from chronic diseases. Cardiovascular health (CVH) was based on the Life’s Essential 8 (LE8) score, a composite of health metrics released by the American Heart Association in 2022. The LE8 was developed to guide research and assessment of cardiovascular health, and includes diet, physical activity, tobacco/nicotine exposure, sleep, body mass index, non-HDL cholesterol, blood glucose, and blood pressure.

In one study, Xuan Wang, MD, a postdoctoral fellow and biostatistician in the department of epidemiology at Tulane University, New Orleans, and colleagues reviewed data from 136,599 adults in the United Kingdom Biobank who were free of cardiovascular disease, diabetes, cancer, and dementia at baseline, and for whom complete LE8 data were available.

CVH was classified as poor, intermediate, and ideal, defined as LE8 scores of less than 50, 50 to 80, and 80 or higher, respectively.

The goal of the study was to examine the role of CVH based on LE8 scores on the percentage of life expectancy free of chronic diseases.

Men and women with ideal CVH averaged 5.2 years and 6.3 years more of total life expectancy at age 50 years, compared with those with poor CVH. Out of total life expectancy, the percentage of life expectancy free of chronic diseases was 75.9% and 83.4% for men and women, respectively, compared with 64.9% and 69.4%, respectively, for men and women with poor CVH.

The researchers also found that disparities in the percentage of disease-free years for both men and women were reduced in the high CVH groups.

The findings were limited by several factors including the use of only CVD, diabetes, cancer, and dementia in the definition of “disease-free life expectancy,” the researchers noted in a press release accompanying the study. Other limitations include the lack of data on e-cigarettes, and the homogeneous White study population. More research is needed in diverse populations who experience a stronger impact from negative social determinants of health, they said.

In a second study, Hao Ma, MD, and colleagues reviewed data from 23,003 adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 with mortality linked to the National Death Index through Dec. 31, 2019. The goal of the second study was to examine the association between CVH based on LE8 scores and life expectancy.

Over a median follow-up of 7.8 years, deaths occurred in 772 men and 587 women, said Dr. Ma, a postdoctoral fellow and biostatistician in epidemiology at Tulane University and coauthor on Dr. Wang’s study.

The estimated life expectancies at age 50 years for men with poor, intermediate, and ideal cardiovascular health based on the LE8 were 25.5 years, 31.2 years, and 33.1 years, respectively.

For women, the corresponding life expectancies for women at age 50 with poor, intermediate, and ideal CVH were 29.5 years, 34.2 years, and 38.4 years, respectively.

Men and women had similar gains in life expectancy from adhering to a heart-healthy lifestyle as defined by the LE8 score that reduced their risk of death from cardiovascular disease (41.8% and 44.1%, respectively).

Associations of cardiovascular health and life expectancy were similar for non-Hispanic Whites and non-Hispanic Blacks, but not among people of Mexican heritage, and more research is needed in diverse populations, the researchers wrote.

The study was limited by several factors including potential changes in cardiovascular health during the follow-up period, and by the limited analysis of racial and ethnic groups to non-Hispanic white, non-Hispanic Black, and people of Mexican heritage because of small sample sizes for other racial/ethnic groups, the researchers noted in a press release accompanying the study.

The message for clinicians and their patients is that adherence to cardiovascular health as defined by the LE8 will help not only extend life, but enhance quality of life, Dr. Xang and Dr. Ma said in an interview. “If your overall CVH score is low, we might be able to focus on one element first and improve them one by one,” they said. Sedentary lifestyle and an unhealthy diet are barriers to improving LE8 metrics that can be addressed, they added.

More research is needed to examine the effects of LE8 on high-risk patients, the researchers told this news organization. “No studies have yet focused on these patients with chronic diseases. We suspect that LE8 will play a role even in these high-risk groups,” they said. Further studies should include diverse populations and evaluations of the association between CVH change and health outcomes, they added.

“Overall, we see this 7.5-year difference [in life expectancy] going from poor to high cardiovascular health,” said Donald M. Lloyd-Jones, MD, of Northwestern University, Chicago, in a video accompanying the presentation of the study findings. The impact on life expectancy is yet another reason to motivate people to improve their cardiovascular health, said Dr. Lloyd-Jones, immediate past president of the American Heart Association and lead author on the writing group for Life’s Essential 8. “The earlier we do this, the better, and the greater the gains in life expectancy we’re likely to see in the U.S. population,” he said.

People maintaining high cardiovascular health into midlife are avoiding not only cardiovascular disease, but other chronic diseases of aging, Dr. Lloyd-Jones added. These conditions are delayed until much later in the lifespan, which allows people to enjoy better quality of life for more of their remaining years, he said.

The meeting was sponsored by the American Heart Association.

Both studies were supported by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health; the Fogarty International Center; and the Tulane Research Centers of Excellence Awards. The researchers had no financial conflicts to disclose.
 

Adults who follow a heart-healthy lifestyle are more likely to live longer and to be free of chronic health conditions, based on data from a pair of related studies from the United States and United Kingdom involving nearly 200,000 individuals.

FatCamera/Getty Images

The studies, presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting in Boston, assessed the impact of cardiovascular health on life expectancy and freedom from chronic diseases. Cardiovascular health (CVH) was based on the Life’s Essential 8 (LE8) score, a composite of health metrics released by the American Heart Association in 2022. The LE8 was developed to guide research and assessment of cardiovascular health, and includes diet, physical activity, tobacco/nicotine exposure, sleep, body mass index, non-HDL cholesterol, blood glucose, and blood pressure.

In one study, Xuan Wang, MD, a postdoctoral fellow and biostatistician in the department of epidemiology at Tulane University, New Orleans, and colleagues reviewed data from 136,599 adults in the United Kingdom Biobank who were free of cardiovascular disease, diabetes, cancer, and dementia at baseline, and for whom complete LE8 data were available.

CVH was classified as poor, intermediate, and ideal, defined as LE8 scores of less than 50, 50 to 80, and 80 or higher, respectively.

The goal of the study was to examine the role of CVH based on LE8 scores on the percentage of life expectancy free of chronic diseases.

Men and women with ideal CVH averaged 5.2 years and 6.3 years more of total life expectancy at age 50 years, compared with those with poor CVH. Out of total life expectancy, the percentage of life expectancy free of chronic diseases was 75.9% and 83.4% for men and women, respectively, compared with 64.9% and 69.4%, respectively, for men and women with poor CVH.

The researchers also found that disparities in the percentage of disease-free years for both men and women were reduced in the high CVH groups.

The findings were limited by several factors including the use of only CVD, diabetes, cancer, and dementia in the definition of “disease-free life expectancy,” the researchers noted in a press release accompanying the study. Other limitations include the lack of data on e-cigarettes, and the homogeneous White study population. More research is needed in diverse populations who experience a stronger impact from negative social determinants of health, they said.

In a second study, Hao Ma, MD, and colleagues reviewed data from 23,003 adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 with mortality linked to the National Death Index through Dec. 31, 2019. The goal of the second study was to examine the association between CVH based on LE8 scores and life expectancy.

Over a median follow-up of 7.8 years, deaths occurred in 772 men and 587 women, said Dr. Ma, a postdoctoral fellow and biostatistician in epidemiology at Tulane University and coauthor on Dr. Wang’s study.

The estimated life expectancies at age 50 years for men with poor, intermediate, and ideal cardiovascular health based on the LE8 were 25.5 years, 31.2 years, and 33.1 years, respectively.

For women, the corresponding life expectancies for women at age 50 with poor, intermediate, and ideal CVH were 29.5 years, 34.2 years, and 38.4 years, respectively.

Men and women had similar gains in life expectancy from adhering to a heart-healthy lifestyle as defined by the LE8 score that reduced their risk of death from cardiovascular disease (41.8% and 44.1%, respectively).

Associations of cardiovascular health and life expectancy were similar for non-Hispanic Whites and non-Hispanic Blacks, but not among people of Mexican heritage, and more research is needed in diverse populations, the researchers wrote.

The study was limited by several factors including potential changes in cardiovascular health during the follow-up period, and by the limited analysis of racial and ethnic groups to non-Hispanic white, non-Hispanic Black, and people of Mexican heritage because of small sample sizes for other racial/ethnic groups, the researchers noted in a press release accompanying the study.

The message for clinicians and their patients is that adherence to cardiovascular health as defined by the LE8 will help not only extend life, but enhance quality of life, Dr. Xang and Dr. Ma said in an interview. “If your overall CVH score is low, we might be able to focus on one element first and improve them one by one,” they said. Sedentary lifestyle and an unhealthy diet are barriers to improving LE8 metrics that can be addressed, they added.

More research is needed to examine the effects of LE8 on high-risk patients, the researchers told this news organization. “No studies have yet focused on these patients with chronic diseases. We suspect that LE8 will play a role even in these high-risk groups,” they said. Further studies should include diverse populations and evaluations of the association between CVH change and health outcomes, they added.

“Overall, we see this 7.5-year difference [in life expectancy] going from poor to high cardiovascular health,” said Donald M. Lloyd-Jones, MD, of Northwestern University, Chicago, in a video accompanying the presentation of the study findings. The impact on life expectancy is yet another reason to motivate people to improve their cardiovascular health, said Dr. Lloyd-Jones, immediate past president of the American Heart Association and lead author on the writing group for Life’s Essential 8. “The earlier we do this, the better, and the greater the gains in life expectancy we’re likely to see in the U.S. population,” he said.

People maintaining high cardiovascular health into midlife are avoiding not only cardiovascular disease, but other chronic diseases of aging, Dr. Lloyd-Jones added. These conditions are delayed until much later in the lifespan, which allows people to enjoy better quality of life for more of their remaining years, he said.

The meeting was sponsored by the American Heart Association.

Both studies were supported by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health; the Fogarty International Center; and the Tulane Research Centers of Excellence Awards. The researchers had no financial conflicts to disclose.