Endocrinology

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

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

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

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

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

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

Fifth pregnancy, first baby.

After four pregnancies resulted in losses – and doing things as natural as possible and leaving it up to the birds, bees, and fate – my husband and I decided to explore in vitro fertilization (IVF).

Drugs to direct my follicles to produce more eggs, an egg retrieval procedure, genetic testing of our embryos, a quick procedure to remove a residual uterine septum from my uterus, drugs to thicken my endometrial lining to prepare my body to receive an embryo, an embryo transfer, steroids to suppress my immune system so my body would accept the pregnancy, blood thinner shots to promote blood flow to the baby, and 10 weeks of progesterone in oil shots later and we’re days away from welcoming our first baby into our lives.

In short, there’s more than one way to define “miracle baby.”

Global estimates say 48 million couples and 186 million individuals struggle with infertility. On average, 2 million infants born in the United States each year are conceived through assisted reproductive technology and the demand for treatments like IVF have doubled in the last decade.

Now the need for treatments outweighs clinician availability. “We have about 1,250 practicing fertility physicians in the U.S. to serve the whole country, which is highly inadequate,” said Eduardo Hariton, MD, a reproductive endocrinology physician in San Francisco and managing director of the U.S. Fertility Innovation Fund. “We have people that want to get care waiting 1 to 3 months to be seen.”

Dr. Hariton explains that U.S. IVF clinics are performing around 250,000 to 300,000 IVF cycles per year and need to be doing a million-plus to meet demand. This, plus the cost of fertility treatments – an average IVF cycle runs $23,500 and the majority of patients need multiple cycles to conceive – keeps the barrier to entry high.

Enter technology: New advances are on the way to help the assisted fertility process to run smoother and be less costly. “The field is really coming into an age of great progress and innovation,” added S. Zev Williams, MD, PhD, chief of the division of reproductive endocrinology and Infertility at Columbia University Irving Medical Center, New York City.

I’m personally grateful that such technology exists. Here is a look at some recent game changers in reproductive tech and what the future may hold.
 

AI will help, of course

Fertility treatments involve endless analysis, diagnosis, and recommendations – dozens if not hundreds of decisions from each physician for each patient. Human action and reaction can affect this process, Dr. Hariton explained.

For example, if he hyperstimulated a woman during the follicle growing stage of her egg retrieval and ended up with eggs too large to retrieve, Dr. Hariton said he may subconsciously be more inclined to be extra cautious with his patients the week after, and vice versa.

This is where AI can help. “Rather than me making decisions from a couple of thousands of cycles of experience, I get to leverage hundreds of thousands of cycles from different providers over different people,” said Dr. Hariton. “I get to use all the data from that patient today – her age, her weight, what happened last cycle, how she’s doing – and make a very objective decision about the optimal time to give that woman or that couple the best outcome possible.”

AI can also assist with tasks like embryo grading. “Once our embryos are made in the lab, we usually have an embryologist looking at those embryos, grading them on a three-variable scale, and then picking the nicest one for transfer,” said Dr. Hariton. Machine learning computer vision software can help doctors select the best embryo.

Many of these AI products are in trials in the United States and some AI-based technology is already being used in fertility labs, especially in other countries. “ALife recently launched a suite of products to help with their decisions during stimulation that can help with the quality KPIs [key performance indicators] in the lab,” said Dr. Hariton. “There’s also a company that does AI-based predictions of success to give patients a better estimate called Univfy.” More AI products are still in development or awaiting Food and Drug Administration clearance.
 

Robots lend a hand

Like artificial intelligence, robots can be a big help in the IVF lab. Columbia University Fertility Center recently became the first to use an articulated (ART) robot to handle precise and highly repetitive work.

“IVF, from the initial point, involves creating these special plates where embryos can grow, and you do that by making little droplets,” said Dr. Williams. “It’s very time-consuming to create tons of these little droplets for the embryos to grow.” Thus, the lab created a robot to help squirt drops of the media substance required to sustain embryos in a way that is 10 times more precise than that of a trained embryologist.

“It’s a win-win because you allow the robots to do things better than a human can and this allows the humans to do things that a robot just can’t do,” explained Dr. Williams. He and his team began using this technology in the beginning of November 2022.

Dr. Williams sees ART robots being used in many more parts of the fertility treatment journey along the way, like preparing eggs after they are retrieved and performing intracytoplasmic sperm injection (ICSI), with the robot injecting the sperm into the egg.

Launching with the plate making, said Dr. Williams, is a low stakes entry point for robotic technology in the lab. “It allows us to introduce robotics to automate and optimize each step along the way, but to do so in the safest possible way.”

Dr. Williams estimates that robots will have their hands on actual eggs and sperm in 5 years.
 

Updates in genetic testing

Currently, if a couple wants to have their embryos genetically tested, also known as preimplantation genetic testing, each embryo must be frozen, then a biopsy of that embryo is performed and sent to the lab.

“It takes time to get the results,” said Dr. Williams. “The whole time you’re waiting, you don’t know if you’re going to have any embryos that are transferable or if next month you’re going to have to do another IVF cycle.”

Columbia researchers recently developed a new in-house test that can determine if a fetus or embryo has the right number of chromosomes. This STORK (Short-read Transpore Rapid Karyotyping) can be performed without freezing embryos and sending them out, which Dr. Williams said can save couples money and time, as they won’t necessarily need to do a separate embryo transfer cycle and can transfer an embryo in the same cycle. “You can test in the morning and transfer in the afternoon,” said Dr. Williams.

The test is currently awaiting approval and will first be used to test miscarriage samples to see if embryos were genetically normal or not, which he said should cost around $200 vs. the $2,000 to $4,000 it can cost to have fetal tissue sent to the lab – and insurance doesn’t cover the procedure until after a second or third miscarriage.

This, said Dr. Williams, should be in the field in less than a year, and he estimates that the test will be used for fresh embryos in about a year and a half.
 

Sperm collection made simpler

Typically, a man delivers a sperm sample in a room at an IVF clinic or by collecting a sample at home and rushing it to the clinic before it degrades, which Dr. Williams said can happen in as little as 15 minutes.

In 2020, Dr. Williams and his team began using a custom at-home sperm collection box that houses sperm in a recyclable foam container that holds a sample cup, which is filled with special sperm-supporting media, at an angle that prevents evaporation and maintains temperature and pH. This allows patients to collect samples in the comfort of their homes and increases the clock to 3 hours.

“It’s great for the patients because it’s much more comfortable,” said Dr. Williams, who notes that having to “perform” on site can be stressful for men. Studies the team has conducted have shown sperm collected in this manner have a better success rate than those collected in the lab, and 90% of Columbia’s Fertility Center patients are now providing sperm samples this way.

Similar innovations to deliver sperm, like Protex, are now on the market, while companies like myLabBox and Legacy are offering at-home sperm testing kits to mail in for a full semen analysis.
 

At-home monitoring: More and better

Wearable reproductive health devices are also helping more women get pregnant. “I am very excited about biometric data harnessed in wearables to predict periods, ovulation, and fertility,” said Amander Clark, PhD, director of the UCLA Center for Reproductive Science, Health, and Education, Los Angeles.

The Tempdrop Fertility and Ovulation Tracker, for instance, is a wearable sensor with an accompanying charting app that helps a woman identify her most fertile days to conceive. The Bellabeat Ivy is a women’s health smart bracelet with a strong focus on tracking a woman’s cycle and fertility, pregnancy, and postnatal symptoms. And Mirvie, which is currently in development, is a blood test that will be able to predict pregnancy complications earlier.

Physicians are also looking to move as much of the lab experience as they can into a patient’s home, which streamlines processes while offering privacy and comfort. For example, Dr. Hariton, who runs a strategic venture capital fund for physicians, said his team is currently working with a company that does remote ultrasounds.

And Mira, an at-home hormone monitor, uses patented AI algorithms to accurately measure the levels of major reproductive health hormones (E3G, LH, PdG, FSH) in urine, said Meir Olcha, MD, chief medical officer at Sama Fertility. The product recently completed a clinical trial, which showed it was a viable alternative to blood serum for patients undergoing IVF.
 

Stem cells could make eggs ageless

Research shows that a woman’s egg quality decreases gradually but significantly starting at age 32 and more rapidly after 37. Sperm quality may also decrease with age. A possible workaround: Scientists are actively researching how to create eggs and sperm from stem cells.

“I think getting eggs from stem cells will happen in the future,” said Dr. Hariton, who notes that this type of technology would be a game changer in his clinic. “It will make some of the hardest diagnoses that I have – which is on a daily basis, ‘I’m so sorry, you’re in premature menopause’ or ‘I don’t think we’re going to be successful getting you pregnant with your own eggs; here are some other options like donor eggs’ – much better,” he added. And stem cells are currently being used to research causes of infertility.

Clinics like UCLA have already been making strides. “We are using stem cells to identify new genes required for reproduction and to define the role of these genes in human fertility and infertility,” said Dr. Clark, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, who recently led a study in this arena. “In vitro gametogenesis (IVG), another stem cell technology, is currently used in the research lab to understand causes of infertility.”

These stem cell-based embryo models, she said, can help researchers understand the first few days of embryo development after an embryo implants and be used to provide critical information on causes of early pregnancy loss or birth defects.

A version of this article appeared on Medscape.com.

Fifth pregnancy, first baby.

After four pregnancies resulted in losses – and doing things as natural as possible and leaving it up to the birds, bees, and fate – my husband and I decided to explore in vitro fertilization (IVF).

Drugs to direct my follicles to produce more eggs, an egg retrieval procedure, genetic testing of our embryos, a quick procedure to remove a residual uterine septum from my uterus, drugs to thicken my endometrial lining to prepare my body to receive an embryo, an embryo transfer, steroids to suppress my immune system so my body would accept the pregnancy, blood thinner shots to promote blood flow to the baby, and 10 weeks of progesterone in oil shots later and we’re days away from welcoming our first baby into our lives.

In short, there’s more than one way to define “miracle baby.”

Global estimates say 48 million couples and 186 million individuals struggle with infertility. On average, 2 million infants born in the United States each year are conceived through assisted reproductive technology and the demand for treatments like IVF have doubled in the last decade.

Now the need for treatments outweighs clinician availability. “We have about 1,250 practicing fertility physicians in the U.S. to serve the whole country, which is highly inadequate,” said Eduardo Hariton, MD, a reproductive endocrinology physician in San Francisco and managing director of the U.S. Fertility Innovation Fund. “We have people that want to get care waiting 1 to 3 months to be seen.”

Dr. Hariton explains that U.S. IVF clinics are performing around 250,000 to 300,000 IVF cycles per year and need to be doing a million-plus to meet demand. This, plus the cost of fertility treatments – an average IVF cycle runs $23,500 and the majority of patients need multiple cycles to conceive – keeps the barrier to entry high.

Enter technology: New advances are on the way to help the assisted fertility process to run smoother and be less costly. “The field is really coming into an age of great progress and innovation,” added S. Zev Williams, MD, PhD, chief of the division of reproductive endocrinology and Infertility at Columbia University Irving Medical Center, New York City.

I’m personally grateful that such technology exists. Here is a look at some recent game changers in reproductive tech and what the future may hold.
 

AI will help, of course

Fertility treatments involve endless analysis, diagnosis, and recommendations – dozens if not hundreds of decisions from each physician for each patient. Human action and reaction can affect this process, Dr. Hariton explained.

For example, if he hyperstimulated a woman during the follicle growing stage of her egg retrieval and ended up with eggs too large to retrieve, Dr. Hariton said he may subconsciously be more inclined to be extra cautious with his patients the week after, and vice versa.

This is where AI can help. “Rather than me making decisions from a couple of thousands of cycles of experience, I get to leverage hundreds of thousands of cycles from different providers over different people,” said Dr. Hariton. “I get to use all the data from that patient today – her age, her weight, what happened last cycle, how she’s doing – and make a very objective decision about the optimal time to give that woman or that couple the best outcome possible.”

AI can also assist with tasks like embryo grading. “Once our embryos are made in the lab, we usually have an embryologist looking at those embryos, grading them on a three-variable scale, and then picking the nicest one for transfer,” said Dr. Hariton. Machine learning computer vision software can help doctors select the best embryo.

Many of these AI products are in trials in the United States and some AI-based technology is already being used in fertility labs, especially in other countries. “ALife recently launched a suite of products to help with their decisions during stimulation that can help with the quality KPIs [key performance indicators] in the lab,” said Dr. Hariton. “There’s also a company that does AI-based predictions of success to give patients a better estimate called Univfy.” More AI products are still in development or awaiting Food and Drug Administration clearance.
 

Robots lend a hand

Like artificial intelligence, robots can be a big help in the IVF lab. Columbia University Fertility Center recently became the first to use an articulated (ART) robot to handle precise and highly repetitive work.

“IVF, from the initial point, involves creating these special plates where embryos can grow, and you do that by making little droplets,” said Dr. Williams. “It’s very time-consuming to create tons of these little droplets for the embryos to grow.” Thus, the lab created a robot to help squirt drops of the media substance required to sustain embryos in a way that is 10 times more precise than that of a trained embryologist.

“It’s a win-win because you allow the robots to do things better than a human can and this allows the humans to do things that a robot just can’t do,” explained Dr. Williams. He and his team began using this technology in the beginning of November 2022.

Dr. Williams sees ART robots being used in many more parts of the fertility treatment journey along the way, like preparing eggs after they are retrieved and performing intracytoplasmic sperm injection (ICSI), with the robot injecting the sperm into the egg.

Launching with the plate making, said Dr. Williams, is a low stakes entry point for robotic technology in the lab. “It allows us to introduce robotics to automate and optimize each step along the way, but to do so in the safest possible way.”

Dr. Williams estimates that robots will have their hands on actual eggs and sperm in 5 years.
 

Updates in genetic testing

Currently, if a couple wants to have their embryos genetically tested, also known as preimplantation genetic testing, each embryo must be frozen, then a biopsy of that embryo is performed and sent to the lab.

“It takes time to get the results,” said Dr. Williams. “The whole time you’re waiting, you don’t know if you’re going to have any embryos that are transferable or if next month you’re going to have to do another IVF cycle.”

Columbia researchers recently developed a new in-house test that can determine if a fetus or embryo has the right number of chromosomes. This STORK (Short-read Transpore Rapid Karyotyping) can be performed without freezing embryos and sending them out, which Dr. Williams said can save couples money and time, as they won’t necessarily need to do a separate embryo transfer cycle and can transfer an embryo in the same cycle. “You can test in the morning and transfer in the afternoon,” said Dr. Williams.

The test is currently awaiting approval and will first be used to test miscarriage samples to see if embryos were genetically normal or not, which he said should cost around $200 vs. the $2,000 to $4,000 it can cost to have fetal tissue sent to the lab – and insurance doesn’t cover the procedure until after a second or third miscarriage.

This, said Dr. Williams, should be in the field in less than a year, and he estimates that the test will be used for fresh embryos in about a year and a half.
 

Sperm collection made simpler

Typically, a man delivers a sperm sample in a room at an IVF clinic or by collecting a sample at home and rushing it to the clinic before it degrades, which Dr. Williams said can happen in as little as 15 minutes.

In 2020, Dr. Williams and his team began using a custom at-home sperm collection box that houses sperm in a recyclable foam container that holds a sample cup, which is filled with special sperm-supporting media, at an angle that prevents evaporation and maintains temperature and pH. This allows patients to collect samples in the comfort of their homes and increases the clock to 3 hours.

“It’s great for the patients because it’s much more comfortable,” said Dr. Williams, who notes that having to “perform” on site can be stressful for men. Studies the team has conducted have shown sperm collected in this manner have a better success rate than those collected in the lab, and 90% of Columbia’s Fertility Center patients are now providing sperm samples this way.

Similar innovations to deliver sperm, like Protex, are now on the market, while companies like myLabBox and Legacy are offering at-home sperm testing kits to mail in for a full semen analysis.
 

At-home monitoring: More and better

Wearable reproductive health devices are also helping more women get pregnant. “I am very excited about biometric data harnessed in wearables to predict periods, ovulation, and fertility,” said Amander Clark, PhD, director of the UCLA Center for Reproductive Science, Health, and Education, Los Angeles.

The Tempdrop Fertility and Ovulation Tracker, for instance, is a wearable sensor with an accompanying charting app that helps a woman identify her most fertile days to conceive. The Bellabeat Ivy is a women’s health smart bracelet with a strong focus on tracking a woman’s cycle and fertility, pregnancy, and postnatal symptoms. And Mirvie, which is currently in development, is a blood test that will be able to predict pregnancy complications earlier.

Physicians are also looking to move as much of the lab experience as they can into a patient’s home, which streamlines processes while offering privacy and comfort. For example, Dr. Hariton, who runs a strategic venture capital fund for physicians, said his team is currently working with a company that does remote ultrasounds.

And Mira, an at-home hormone monitor, uses patented AI algorithms to accurately measure the levels of major reproductive health hormones (E3G, LH, PdG, FSH) in urine, said Meir Olcha, MD, chief medical officer at Sama Fertility. The product recently completed a clinical trial, which showed it was a viable alternative to blood serum for patients undergoing IVF.
 

Stem cells could make eggs ageless

Research shows that a woman’s egg quality decreases gradually but significantly starting at age 32 and more rapidly after 37. Sperm quality may also decrease with age. A possible workaround: Scientists are actively researching how to create eggs and sperm from stem cells.

“I think getting eggs from stem cells will happen in the future,” said Dr. Hariton, who notes that this type of technology would be a game changer in his clinic. “It will make some of the hardest diagnoses that I have – which is on a daily basis, ‘I’m so sorry, you’re in premature menopause’ or ‘I don’t think we’re going to be successful getting you pregnant with your own eggs; here are some other options like donor eggs’ – much better,” he added. And stem cells are currently being used to research causes of infertility.

Clinics like UCLA have already been making strides. “We are using stem cells to identify new genes required for reproduction and to define the role of these genes in human fertility and infertility,” said Dr. Clark, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, who recently led a study in this arena. “In vitro gametogenesis (IVG), another stem cell technology, is currently used in the research lab to understand causes of infertility.”

These stem cell-based embryo models, she said, can help researchers understand the first few days of embryo development after an embryo implants and be used to provide critical information on causes of early pregnancy loss or birth defects.

A version of this article appeared on Medscape.com.

Fifth pregnancy, first baby.

After four pregnancies resulted in losses – and doing things as natural as possible and leaving it up to the birds, bees, and fate – my husband and I decided to explore in vitro fertilization (IVF).

Drugs to direct my follicles to produce more eggs, an egg retrieval procedure, genetic testing of our embryos, a quick procedure to remove a residual uterine septum from my uterus, drugs to thicken my endometrial lining to prepare my body to receive an embryo, an embryo transfer, steroids to suppress my immune system so my body would accept the pregnancy, blood thinner shots to promote blood flow to the baby, and 10 weeks of progesterone in oil shots later and we’re days away from welcoming our first baby into our lives.

In short, there’s more than one way to define “miracle baby.”

Global estimates say 48 million couples and 186 million individuals struggle with infertility. On average, 2 million infants born in the United States each year are conceived through assisted reproductive technology and the demand for treatments like IVF have doubled in the last decade.

Now the need for treatments outweighs clinician availability. “We have about 1,250 practicing fertility physicians in the U.S. to serve the whole country, which is highly inadequate,” said Eduardo Hariton, MD, a reproductive endocrinology physician in San Francisco and managing director of the U.S. Fertility Innovation Fund. “We have people that want to get care waiting 1 to 3 months to be seen.”

Dr. Hariton explains that U.S. IVF clinics are performing around 250,000 to 300,000 IVF cycles per year and need to be doing a million-plus to meet demand. This, plus the cost of fertility treatments – an average IVF cycle runs $23,500 and the majority of patients need multiple cycles to conceive – keeps the barrier to entry high.

Enter technology: New advances are on the way to help the assisted fertility process to run smoother and be less costly. “The field is really coming into an age of great progress and innovation,” added S. Zev Williams, MD, PhD, chief of the division of reproductive endocrinology and Infertility at Columbia University Irving Medical Center, New York City.

I’m personally grateful that such technology exists. Here is a look at some recent game changers in reproductive tech and what the future may hold.
 

AI will help, of course

Fertility treatments involve endless analysis, diagnosis, and recommendations – dozens if not hundreds of decisions from each physician for each patient. Human action and reaction can affect this process, Dr. Hariton explained.

For example, if he hyperstimulated a woman during the follicle growing stage of her egg retrieval and ended up with eggs too large to retrieve, Dr. Hariton said he may subconsciously be more inclined to be extra cautious with his patients the week after, and vice versa.

This is where AI can help. “Rather than me making decisions from a couple of thousands of cycles of experience, I get to leverage hundreds of thousands of cycles from different providers over different people,” said Dr. Hariton. “I get to use all the data from that patient today – her age, her weight, what happened last cycle, how she’s doing – and make a very objective decision about the optimal time to give that woman or that couple the best outcome possible.”

AI can also assist with tasks like embryo grading. “Once our embryos are made in the lab, we usually have an embryologist looking at those embryos, grading them on a three-variable scale, and then picking the nicest one for transfer,” said Dr. Hariton. Machine learning computer vision software can help doctors select the best embryo.

Many of these AI products are in trials in the United States and some AI-based technology is already being used in fertility labs, especially in other countries. “ALife recently launched a suite of products to help with their decisions during stimulation that can help with the quality KPIs [key performance indicators] in the lab,” said Dr. Hariton. “There’s also a company that does AI-based predictions of success to give patients a better estimate called Univfy.” More AI products are still in development or awaiting Food and Drug Administration clearance.
 

Robots lend a hand

Like artificial intelligence, robots can be a big help in the IVF lab. Columbia University Fertility Center recently became the first to use an articulated (ART) robot to handle precise and highly repetitive work.

“IVF, from the initial point, involves creating these special plates where embryos can grow, and you do that by making little droplets,” said Dr. Williams. “It’s very time-consuming to create tons of these little droplets for the embryos to grow.” Thus, the lab created a robot to help squirt drops of the media substance required to sustain embryos in a way that is 10 times more precise than that of a trained embryologist.

“It’s a win-win because you allow the robots to do things better than a human can and this allows the humans to do things that a robot just can’t do,” explained Dr. Williams. He and his team began using this technology in the beginning of November 2022.

Dr. Williams sees ART robots being used in many more parts of the fertility treatment journey along the way, like preparing eggs after they are retrieved and performing intracytoplasmic sperm injection (ICSI), with the robot injecting the sperm into the egg.

Launching with the plate making, said Dr. Williams, is a low stakes entry point for robotic technology in the lab. “It allows us to introduce robotics to automate and optimize each step along the way, but to do so in the safest possible way.”

Dr. Williams estimates that robots will have their hands on actual eggs and sperm in 5 years.
 

Updates in genetic testing

Currently, if a couple wants to have their embryos genetically tested, also known as preimplantation genetic testing, each embryo must be frozen, then a biopsy of that embryo is performed and sent to the lab.

“It takes time to get the results,” said Dr. Williams. “The whole time you’re waiting, you don’t know if you’re going to have any embryos that are transferable or if next month you’re going to have to do another IVF cycle.”

Columbia researchers recently developed a new in-house test that can determine if a fetus or embryo has the right number of chromosomes. This STORK (Short-read Transpore Rapid Karyotyping) can be performed without freezing embryos and sending them out, which Dr. Williams said can save couples money and time, as they won’t necessarily need to do a separate embryo transfer cycle and can transfer an embryo in the same cycle. “You can test in the morning and transfer in the afternoon,” said Dr. Williams.

The test is currently awaiting approval and will first be used to test miscarriage samples to see if embryos were genetically normal or not, which he said should cost around $200 vs. the $2,000 to $4,000 it can cost to have fetal tissue sent to the lab – and insurance doesn’t cover the procedure until after a second or third miscarriage.

This, said Dr. Williams, should be in the field in less than a year, and he estimates that the test will be used for fresh embryos in about a year and a half.
 

Sperm collection made simpler

Typically, a man delivers a sperm sample in a room at an IVF clinic or by collecting a sample at home and rushing it to the clinic before it degrades, which Dr. Williams said can happen in as little as 15 minutes.

In 2020, Dr. Williams and his team began using a custom at-home sperm collection box that houses sperm in a recyclable foam container that holds a sample cup, which is filled with special sperm-supporting media, at an angle that prevents evaporation and maintains temperature and pH. This allows patients to collect samples in the comfort of their homes and increases the clock to 3 hours.

“It’s great for the patients because it’s much more comfortable,” said Dr. Williams, who notes that having to “perform” on site can be stressful for men. Studies the team has conducted have shown sperm collected in this manner have a better success rate than those collected in the lab, and 90% of Columbia’s Fertility Center patients are now providing sperm samples this way.

Similar innovations to deliver sperm, like Protex, are now on the market, while companies like myLabBox and Legacy are offering at-home sperm testing kits to mail in for a full semen analysis.
 

At-home monitoring: More and better

Wearable reproductive health devices are also helping more women get pregnant. “I am very excited about biometric data harnessed in wearables to predict periods, ovulation, and fertility,” said Amander Clark, PhD, director of the UCLA Center for Reproductive Science, Health, and Education, Los Angeles.

The Tempdrop Fertility and Ovulation Tracker, for instance, is a wearable sensor with an accompanying charting app that helps a woman identify her most fertile days to conceive. The Bellabeat Ivy is a women’s health smart bracelet with a strong focus on tracking a woman’s cycle and fertility, pregnancy, and postnatal symptoms. And Mirvie, which is currently in development, is a blood test that will be able to predict pregnancy complications earlier.

Physicians are also looking to move as much of the lab experience as they can into a patient’s home, which streamlines processes while offering privacy and comfort. For example, Dr. Hariton, who runs a strategic venture capital fund for physicians, said his team is currently working with a company that does remote ultrasounds.

And Mira, an at-home hormone monitor, uses patented AI algorithms to accurately measure the levels of major reproductive health hormones (E3G, LH, PdG, FSH) in urine, said Meir Olcha, MD, chief medical officer at Sama Fertility. The product recently completed a clinical trial, which showed it was a viable alternative to blood serum for patients undergoing IVF.
 

Stem cells could make eggs ageless

Research shows that a woman’s egg quality decreases gradually but significantly starting at age 32 and more rapidly after 37. Sperm quality may also decrease with age. A possible workaround: Scientists are actively researching how to create eggs and sperm from stem cells.

“I think getting eggs from stem cells will happen in the future,” said Dr. Hariton, who notes that this type of technology would be a game changer in his clinic. “It will make some of the hardest diagnoses that I have – which is on a daily basis, ‘I’m so sorry, you’re in premature menopause’ or ‘I don’t think we’re going to be successful getting you pregnant with your own eggs; here are some other options like donor eggs’ – much better,” he added. And stem cells are currently being used to research causes of infertility.

Clinics like UCLA have already been making strides. “We are using stem cells to identify new genes required for reproduction and to define the role of these genes in human fertility and infertility,” said Dr. Clark, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, who recently led a study in this arena. “In vitro gametogenesis (IVG), another stem cell technology, is currently used in the research lab to understand causes of infertility.”

These stem cell-based embryo models, she said, can help researchers understand the first few days of embryo development after an embryo implants and be used to provide critical information on causes of early pregnancy loss or birth defects.

A version of this article appeared on Medscape.com.

TOPLINE:

Chronic pancreatitis raises the risk for pregnancy complications, including gestational diabetes, gestational hypertensive complications, and preterm labor, according to a large study.

METHODOLOGY:

• A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted.
• The sample included 3,094 pregnancies with chronic pancreatitis and roughly 40.8 million pregnancies without this condition.
• The study focused on primary maternal outcomes and primary perinatal outcomes in pregnancies affected by chronic pancreatitis after accounting for relevant covariates.

TAKEAWAY:

• Chronic pancreatitis pregnancies had elevated rates of gestational diabetes (adjusted odds ratio, 1.63), gestational hypertensive complications (aOR, 2.48), preterm labor (aOR, 3.10), and small size for gestational age (aOR, 2.40).
• Women with chronic pancreatitis and a history of renal failure were more prone to gestational hypertensive complications (aOR, 20.09).
• Women with alcohol-induced chronic pancreatitis had a 17-fold higher risk for fetal death (aOR, 17.15).
• Pregnancies with chronic pancreatitis were associated with longer hospital stays and higher hospital costs.

IN PRACTICE:

“Our study provides novel insights into the impact of chronic pancreatitis on maternal and fetal health. The implications of our findings are critical for health care professionals, particularly those involved in preconception counseling. Pregnant women with chronic pancreatitis should be under the care of a multidisciplinary team of health care providers,” the authors advise.

SOURCE:

The study was led by Chengu Niu, MD, with Rochester General Hospital, Rochester, N.Y. It was published online July 18 in Digestive and Liver Disease. The study had no specific funding.

LIMITATIONS:

The authors note potential inaccuracies because of coding in the National Inpatient Sample database, a lack of detailed information regarding medication use, and a lack of follow-up clinical information. The findings are specific to the United States and may not be applicable to other countries.

DISCLOSURES:

The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Chronic pancreatitis raises the risk for pregnancy complications, including gestational diabetes, gestational hypertensive complications, and preterm labor, according to a large study.

METHODOLOGY:

• A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted.
• The sample included 3,094 pregnancies with chronic pancreatitis and roughly 40.8 million pregnancies without this condition.
• The study focused on primary maternal outcomes and primary perinatal outcomes in pregnancies affected by chronic pancreatitis after accounting for relevant covariates.

TAKEAWAY:

• Chronic pancreatitis pregnancies had elevated rates of gestational diabetes (adjusted odds ratio, 1.63), gestational hypertensive complications (aOR, 2.48), preterm labor (aOR, 3.10), and small size for gestational age (aOR, 2.40).
• Women with chronic pancreatitis and a history of renal failure were more prone to gestational hypertensive complications (aOR, 20.09).
• Women with alcohol-induced chronic pancreatitis had a 17-fold higher risk for fetal death (aOR, 17.15).
• Pregnancies with chronic pancreatitis were associated with longer hospital stays and higher hospital costs.

IN PRACTICE:

“Our study provides novel insights into the impact of chronic pancreatitis on maternal and fetal health. The implications of our findings are critical for health care professionals, particularly those involved in preconception counseling. Pregnant women with chronic pancreatitis should be under the care of a multidisciplinary team of health care providers,” the authors advise.

SOURCE:

The study was led by Chengu Niu, MD, with Rochester General Hospital, Rochester, N.Y. It was published online July 18 in Digestive and Liver Disease. The study had no specific funding.

LIMITATIONS:

The authors note potential inaccuracies because of coding in the National Inpatient Sample database, a lack of detailed information regarding medication use, and a lack of follow-up clinical information. The findings are specific to the United States and may not be applicable to other countries.

DISCLOSURES:

The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Chronic pancreatitis raises the risk for pregnancy complications, including gestational diabetes, gestational hypertensive complications, and preterm labor, according to a large study.

METHODOLOGY:

• A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted.
• The sample included 3,094 pregnancies with chronic pancreatitis and roughly 40.8 million pregnancies without this condition.
• The study focused on primary maternal outcomes and primary perinatal outcomes in pregnancies affected by chronic pancreatitis after accounting for relevant covariates.

TAKEAWAY:

• Chronic pancreatitis pregnancies had elevated rates of gestational diabetes (adjusted odds ratio, 1.63), gestational hypertensive complications (aOR, 2.48), preterm labor (aOR, 3.10), and small size for gestational age (aOR, 2.40).
• Women with chronic pancreatitis and a history of renal failure were more prone to gestational hypertensive complications (aOR, 20.09).
• Women with alcohol-induced chronic pancreatitis had a 17-fold higher risk for fetal death (aOR, 17.15).
• Pregnancies with chronic pancreatitis were associated with longer hospital stays and higher hospital costs.

IN PRACTICE:

“Our study provides novel insights into the impact of chronic pancreatitis on maternal and fetal health. The implications of our findings are critical for health care professionals, particularly those involved in preconception counseling. Pregnant women with chronic pancreatitis should be under the care of a multidisciplinary team of health care providers,” the authors advise.

SOURCE:

The study was led by Chengu Niu, MD, with Rochester General Hospital, Rochester, N.Y. It was published online July 18 in Digestive and Liver Disease. The study had no specific funding.

LIMITATIONS:

The authors note potential inaccuracies because of coding in the National Inpatient Sample database, a lack of detailed information regarding medication use, and a lack of follow-up clinical information. The findings are specific to the United States and may not be applicable to other countries.

DISCLOSURES:

The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

Stiff arteries may cause, rather than be a consequence of, metabolic syndrome, results of a longitudinal birth cohort study show.

New research published in the American Journal of Physiology found that arterial stiffness occurred before the presence of metabolic syndrome. A progressive rise in stiffness was associated with a cumulative increase in risk for the condition among the 3,862 people studied over a 7-year period starting in late adolescence. 

Results revealed a notable sex difference: Arterial stiffness increased the risk for metabolic syndrome by 9% for males but only by 1% for females. Males were also five times more likely than females to have metabolic syndrome.

“It seems metabolic syndrome has a new risk factor we haven’t thought about,” said author Andrew O. Agbaje, MD, clinical epidemiologist and researcher, University of Eastern Finland, Kuopio.

Arterial stiffness previously was associated with metabolic syndrome in numerous studies. But the new work is the first to find evidence for causality, Dr. Agbaje said in an interview.

“Interventions have focused on addressing the components of metabolic syndrome such as obesity, dyslipidemia, hyperglycemia, and hypertension,” Dr. Agbaje said. “But arterial stiffness may independently cause metabolic syndrome in 1 out of 10 male teens. I encourage clinicians to think about its role in preventing and managing metabolic syndrome, not just as a consequence but as a cause.”

The results have important implications for physicians, according to Sissi Cossio, MD, pediatric endocrinologist, Pediatrix Medical Group, Fort Lauderdale, Fla.

“The fact that arterial stiffness progression preceded metabolic syndrome is important because it could be used as an earlier detection marker of disease,” Dr. Cossio said.

To conduct the study, Dr. Agbaje and his research team used data collected by the Avon Longitudinal Study of Parents and Children at the University of Bristol in England. Arterial stiffness was measured using carotid-femoral pulse wave velocity, the speed of blood flow from the upper to the lower aorta. They assessed for metabolic syndrome by the presence of three or more risk factors, including high cholesterol, high triglycerides, and high trunk fat mass.

Participants were studied starting in gestation in the early 1990s, and were measured for arterial stiffness and metabolic syndrome starting at age 17 through age 24.

The overall risk for metabolic syndrome doubled within the 7-year study period of follow-up between 2009 and 2017, indicating that early intervention during adolescence is essential. 

Dr. Agbaje recommended that physicians start treating arterial stiffness and other markers of metabolic syndrome as early as possible, noting that, “potentially irreversible cardiovascular health damage might occur after age 17.” 

Arterial stiffness can be negated through physical activity and dietary changes that lower inflammation. Physicians should refer at-risk teens to a preventative clinic where they can be monitored and receive repeated measurements of arterial stiffness, lipid levels, blood pressure, glucose levels, and obesity every 3 months, Dr. Agbaje said.

“The health progress made after a year would be an indicator for physicians whether a more aggressive therapeutic approach is needed since it takes about 7 years for the risk of metabolic syndrome attributed to arterial stiffness to worsen remarkably in the young population,” he said.

Dr. Agbaje pointed to a few potential pathways through which arterial stiffness might create a disease cascade. Stiffer arteries disrupt blood flow to the liver and pancreas, which could adversely affect their functioning, he said. Damage to these organs may increase insulin and LDL cholesterol blood levels, increasing the risk for metabolic syndrome.

Arterial stiffness also can lead to higher blood pressure and insulin resistance, potentially inducing musculogenesis and vasculogenesis. The resulting excessive muscle mass may also increase the risk for the condition, he said.

Dr. Cossio acknowledged that treatments for metabolic syndrome become less effective with age, but emphasized that reversal is possible in adults with lifestyle changes and medications.

“Early detection will give patients the best chance at reversing the disease, and [primary care physicians] are a key factor in this process,” she said.

Dr. Cossio said that at-risk teens should receive treatment in a weight loss or endocrinology clinic. Treatment may include behavioral, surgical, and pharmacotherapeutic interventions.

“Teens with signs of insulin resistance and impaired fasting glucose, acanthosis, or prediabetes, should start metformin as the first line of therapy,” Dr. Cossio said. 

For weight management, she recommends antiobesity medications such as liraglutide, semaglutide, and the combination of phentermine/topiramate in children aged 12 years or older. In teenagers 16 years or older, phentermine alone is another option.

The research group that conducted the study reported received funding from the Jenny and Antti Wihuri Foundation, the North Savo Regional Fund and Central Finnish Cultural Foundation, the Aarne Koskelo Foundation, the Foundation for Pediatric Research, and the Finnish Foundation for Cardiovascular Research, among others. The authors declared no conflicts of interest, financial or otherwise.
 

A version of this article appeared on Medscape.com.

Stiff arteries may cause, rather than be a consequence of, metabolic syndrome, results of a longitudinal birth cohort study show.

New research published in the American Journal of Physiology found that arterial stiffness occurred before the presence of metabolic syndrome. A progressive rise in stiffness was associated with a cumulative increase in risk for the condition among the 3,862 people studied over a 7-year period starting in late adolescence. 

Results revealed a notable sex difference: Arterial stiffness increased the risk for metabolic syndrome by 9% for males but only by 1% for females. Males were also five times more likely than females to have metabolic syndrome.

“It seems metabolic syndrome has a new risk factor we haven’t thought about,” said author Andrew O. Agbaje, MD, clinical epidemiologist and researcher, University of Eastern Finland, Kuopio.

Arterial stiffness previously was associated with metabolic syndrome in numerous studies. But the new work is the first to find evidence for causality, Dr. Agbaje said in an interview.

“Interventions have focused on addressing the components of metabolic syndrome such as obesity, dyslipidemia, hyperglycemia, and hypertension,” Dr. Agbaje said. “But arterial stiffness may independently cause metabolic syndrome in 1 out of 10 male teens. I encourage clinicians to think about its role in preventing and managing metabolic syndrome, not just as a consequence but as a cause.”

The results have important implications for physicians, according to Sissi Cossio, MD, pediatric endocrinologist, Pediatrix Medical Group, Fort Lauderdale, Fla.

“The fact that arterial stiffness progression preceded metabolic syndrome is important because it could be used as an earlier detection marker of disease,” Dr. Cossio said.

To conduct the study, Dr. Agbaje and his research team used data collected by the Avon Longitudinal Study of Parents and Children at the University of Bristol in England. Arterial stiffness was measured using carotid-femoral pulse wave velocity, the speed of blood flow from the upper to the lower aorta. They assessed for metabolic syndrome by the presence of three or more risk factors, including high cholesterol, high triglycerides, and high trunk fat mass.

Participants were studied starting in gestation in the early 1990s, and were measured for arterial stiffness and metabolic syndrome starting at age 17 through age 24.

The overall risk for metabolic syndrome doubled within the 7-year study period of follow-up between 2009 and 2017, indicating that early intervention during adolescence is essential. 

Dr. Agbaje recommended that physicians start treating arterial stiffness and other markers of metabolic syndrome as early as possible, noting that, “potentially irreversible cardiovascular health damage might occur after age 17.” 

Arterial stiffness can be negated through physical activity and dietary changes that lower inflammation. Physicians should refer at-risk teens to a preventative clinic where they can be monitored and receive repeated measurements of arterial stiffness, lipid levels, blood pressure, glucose levels, and obesity every 3 months, Dr. Agbaje said.

“The health progress made after a year would be an indicator for physicians whether a more aggressive therapeutic approach is needed since it takes about 7 years for the risk of metabolic syndrome attributed to arterial stiffness to worsen remarkably in the young population,” he said.

Dr. Agbaje pointed to a few potential pathways through which arterial stiffness might create a disease cascade. Stiffer arteries disrupt blood flow to the liver and pancreas, which could adversely affect their functioning, he said. Damage to these organs may increase insulin and LDL cholesterol blood levels, increasing the risk for metabolic syndrome.

Arterial stiffness also can lead to higher blood pressure and insulin resistance, potentially inducing musculogenesis and vasculogenesis. The resulting excessive muscle mass may also increase the risk for the condition, he said.

Dr. Cossio acknowledged that treatments for metabolic syndrome become less effective with age, but emphasized that reversal is possible in adults with lifestyle changes and medications.

“Early detection will give patients the best chance at reversing the disease, and [primary care physicians] are a key factor in this process,” she said.

Dr. Cossio said that at-risk teens should receive treatment in a weight loss or endocrinology clinic. Treatment may include behavioral, surgical, and pharmacotherapeutic interventions.

“Teens with signs of insulin resistance and impaired fasting glucose, acanthosis, or prediabetes, should start metformin as the first line of therapy,” Dr. Cossio said. 

For weight management, she recommends antiobesity medications such as liraglutide, semaglutide, and the combination of phentermine/topiramate in children aged 12 years or older. In teenagers 16 years or older, phentermine alone is another option.

The research group that conducted the study reported received funding from the Jenny and Antti Wihuri Foundation, the North Savo Regional Fund and Central Finnish Cultural Foundation, the Aarne Koskelo Foundation, the Foundation for Pediatric Research, and the Finnish Foundation for Cardiovascular Research, among others. The authors declared no conflicts of interest, financial or otherwise.
 

A version of this article appeared on Medscape.com.

Stiff arteries may cause, rather than be a consequence of, metabolic syndrome, results of a longitudinal birth cohort study show.

New research published in the American Journal of Physiology found that arterial stiffness occurred before the presence of metabolic syndrome. A progressive rise in stiffness was associated with a cumulative increase in risk for the condition among the 3,862 people studied over a 7-year period starting in late adolescence. 

Results revealed a notable sex difference: Arterial stiffness increased the risk for metabolic syndrome by 9% for males but only by 1% for females. Males were also five times more likely than females to have metabolic syndrome.

“It seems metabolic syndrome has a new risk factor we haven’t thought about,” said author Andrew O. Agbaje, MD, clinical epidemiologist and researcher, University of Eastern Finland, Kuopio.

Arterial stiffness previously was associated with metabolic syndrome in numerous studies. But the new work is the first to find evidence for causality, Dr. Agbaje said in an interview.

“Interventions have focused on addressing the components of metabolic syndrome such as obesity, dyslipidemia, hyperglycemia, and hypertension,” Dr. Agbaje said. “But arterial stiffness may independently cause metabolic syndrome in 1 out of 10 male teens. I encourage clinicians to think about its role in preventing and managing metabolic syndrome, not just as a consequence but as a cause.”

The results have important implications for physicians, according to Sissi Cossio, MD, pediatric endocrinologist, Pediatrix Medical Group, Fort Lauderdale, Fla.

“The fact that arterial stiffness progression preceded metabolic syndrome is important because it could be used as an earlier detection marker of disease,” Dr. Cossio said.

To conduct the study, Dr. Agbaje and his research team used data collected by the Avon Longitudinal Study of Parents and Children at the University of Bristol in England. Arterial stiffness was measured using carotid-femoral pulse wave velocity, the speed of blood flow from the upper to the lower aorta. They assessed for metabolic syndrome by the presence of three or more risk factors, including high cholesterol, high triglycerides, and high trunk fat mass.

Participants were studied starting in gestation in the early 1990s, and were measured for arterial stiffness and metabolic syndrome starting at age 17 through age 24.

The overall risk for metabolic syndrome doubled within the 7-year study period of follow-up between 2009 and 2017, indicating that early intervention during adolescence is essential. 

Dr. Agbaje recommended that physicians start treating arterial stiffness and other markers of metabolic syndrome as early as possible, noting that, “potentially irreversible cardiovascular health damage might occur after age 17.” 

Arterial stiffness can be negated through physical activity and dietary changes that lower inflammation. Physicians should refer at-risk teens to a preventative clinic where they can be monitored and receive repeated measurements of arterial stiffness, lipid levels, blood pressure, glucose levels, and obesity every 3 months, Dr. Agbaje said.

“The health progress made after a year would be an indicator for physicians whether a more aggressive therapeutic approach is needed since it takes about 7 years for the risk of metabolic syndrome attributed to arterial stiffness to worsen remarkably in the young population,” he said.

Dr. Agbaje pointed to a few potential pathways through which arterial stiffness might create a disease cascade. Stiffer arteries disrupt blood flow to the liver and pancreas, which could adversely affect their functioning, he said. Damage to these organs may increase insulin and LDL cholesterol blood levels, increasing the risk for metabolic syndrome.

Arterial stiffness also can lead to higher blood pressure and insulin resistance, potentially inducing musculogenesis and vasculogenesis. The resulting excessive muscle mass may also increase the risk for the condition, he said.

Dr. Cossio acknowledged that treatments for metabolic syndrome become less effective with age, but emphasized that reversal is possible in adults with lifestyle changes and medications.

“Early detection will give patients the best chance at reversing the disease, and [primary care physicians] are a key factor in this process,” she said.

Dr. Cossio said that at-risk teens should receive treatment in a weight loss or endocrinology clinic. Treatment may include behavioral, surgical, and pharmacotherapeutic interventions.

“Teens with signs of insulin resistance and impaired fasting glucose, acanthosis, or prediabetes, should start metformin as the first line of therapy,” Dr. Cossio said. 

For weight management, she recommends antiobesity medications such as liraglutide, semaglutide, and the combination of phentermine/topiramate in children aged 12 years or older. In teenagers 16 years or older, phentermine alone is another option.

The research group that conducted the study reported received funding from the Jenny and Antti Wihuri Foundation, the North Savo Regional Fund and Central Finnish Cultural Foundation, the Aarne Koskelo Foundation, the Foundation for Pediatric Research, and the Finnish Foundation for Cardiovascular Research, among others. The authors declared no conflicts of interest, financial or otherwise.
 

A version of this article appeared on Medscape.com.

Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?

Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.

Three recently published studies investigated this:

• The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
• A large observational study out of China in patients with KOA and type 2 diabetes.
• A preclinical trial of liraglutide in mouse models of KOA.

The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.

This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
 

The big picture, as seen by two experts

The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.

ljubaphoto/E+/Getty Images

Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.

Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.

“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.

Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”

Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.  

Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.

Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.

“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.

They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.

He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
 

Three published studies

LOSEIT: RCT of liraglutide for pain and weight control in KOA

Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.

All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.

Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.

From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.

“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.

“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”

The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.

“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.

Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.

The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.

Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”

Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.

In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
 

Observational study of patients with diabetes and KOA

Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.

They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.

The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m², and a mean A1c of 7.3%.

“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.

The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).

Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.

“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.

They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”

They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.

Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m² and has osteoarthritis, he or she could still benefit from weight loss, he said.
 

Liraglutide and pain-related behavior in mouse models of OA

Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.

In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.

The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).

They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.

“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”

Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
 

Two trials near completion, one is upcoming

Phase 1 and 2 trials of 4P-004

“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.  

The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.

The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
 

Phase 3 trial of semaglutide for KOA

Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.

Eligible patients were aged 18 and older, with BMI > 30 kg/m² and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.

The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.

Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?

Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.

Three recently published studies investigated this:

• The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
• A large observational study out of China in patients with KOA and type 2 diabetes.
• A preclinical trial of liraglutide in mouse models of KOA.

The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.

This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
 

The big picture, as seen by two experts

The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.

ljubaphoto/E+/Getty Images

Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.

Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.

“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.

Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”

Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.  

Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.

Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.

“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.

They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.

He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
 

Three published studies

LOSEIT: RCT of liraglutide for pain and weight control in KOA

Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.

All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.

Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.

From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.

“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.

“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”

The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.

“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.

Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.

The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.

Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”

Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.

In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
 

Observational study of patients with diabetes and KOA

Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.

They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.

The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m², and a mean A1c of 7.3%.

“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.

The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).

Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.

“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.

They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”

They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.

Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m² and has osteoarthritis, he or she could still benefit from weight loss, he said.
 

Liraglutide and pain-related behavior in mouse models of OA

Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.

In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.

The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).

They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.

“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”

Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
 

Two trials near completion, one is upcoming

Phase 1 and 2 trials of 4P-004

“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.  

The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.

The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
 

Phase 3 trial of semaglutide for KOA

Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.

Eligible patients were aged 18 and older, with BMI > 30 kg/m² and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.

The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.

Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?

Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.

Three recently published studies investigated this:

• The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
• A large observational study out of China in patients with KOA and type 2 diabetes.
• A preclinical trial of liraglutide in mouse models of KOA.

The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.

This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
 

The big picture, as seen by two experts

The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.

ljubaphoto/E+/Getty Images

Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.

Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.

“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.

Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”

Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.  

Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.

Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.

“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.

They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.

He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
 

Three published studies

LOSEIT: RCT of liraglutide for pain and weight control in KOA

Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.

All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.

Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.

From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.

“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.

“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”

The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.

“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.

Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.

The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.

Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”

Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.

In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
 

Observational study of patients with diabetes and KOA

Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.

They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.

The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m², and a mean A1c of 7.3%.

“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.

The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).

Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.

“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.

They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”

They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.

Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m² and has osteoarthritis, he or she could still benefit from weight loss, he said.
 

Liraglutide and pain-related behavior in mouse models of OA

Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.

In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.

The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).

They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.

“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”

Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
 

Two trials near completion, one is upcoming

Phase 1 and 2 trials of 4P-004

“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.  

The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.

The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
 

Phase 3 trial of semaglutide for KOA

Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.

Eligible patients were aged 18 and older, with BMI > 30 kg/m² and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.

The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.

Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

In Colorado and Wyoming, nearly every baby born since 2020 is tested for signs of a mutation in the SMN1 gene, an indicator of spinal muscular atrophy (SMA). And in 4 years, genetic counselor Melissa Gibbons has seen 24 positive results. She has prepped 24 different pediatricians and family doctors to deliver the news: A seemingly perfect newborn likely has a lethal genetic disease.

Most of these clinicians had never cared for a child with SMA before, nor did they know that lifesaving gene therapy for the condition now exists. Still, the physicians were foundational to getting babies emergency treatment and monitoring the child’s safety after the fact.

“They are boots on the ground for this kind of [work],” Ms. Gibbons, who is the newborn screen coordinator for SMA in both states, told this news organization. “I’m not even sure they realize it.” As of today, the U.S. Food and Drug Administration has approved 16 gene therapies for the treatment of rare and debilitating diseases once considered lethal, such as SMA and cerebral adrenoleukodystrophy.

The newest addition to the list of approvals is Elevidys, Sarepta’s gene therapy for Duchenne muscular dystrophy (DMD). These conditions can now be mitigated, abated for years at a time, and even cured using treatments that tweak a patient’s DNA or RNA.

Hundreds of treatments are under development using the same mechanism. Viruses, liposomes, and other vectors of all kinds are being used to usher new genes into cells, correcting faulty copies or equipping a cell to fight disease. Cells gain the ability to make lifesaving proteins – proteins that heal wounds, restore muscle function, and fight cancer.

Within the decade, a significant fraction of the pediatric population will have gone through gene therapy, experts told this news organization. And primary care stands to be a linchpin in the scale-up of this kind of precision genetic medicine. Pediatricians and general practitioners will be central to finding and monitoring the patients that need these treatments. But the time and support doctors will need to fill that role remain scarce.

“This is a world we are creating right now, quite literally,” said Stanley Nelson, MD, director of the center for Duchenne muscular dystrophy at the University of California, Los Angeles. These cases – some before gene therapy and some after – will show up in primary care offices before the textbook is written.
 

Unknown side effects, new diseases

Even now, gene therapy is sequestered away in large academic medical research centers. The diagnosis, decision-making, and aftercare are handled by subspecialists working on clinical trials. While the research is ongoing, trial sponsors are keeping a close eye on enrolled patients. But that’s only until these drugs get market approval, Phil Beales, MD, chief medical officer at Congenica, a digital health company specializing in genome analysis support, said. Afterward, “the trialists will no longer have a role in looking after those patients.”

At that point, the role of primary care clinicians will be critically important. Although they probably will not manage gene-therapy patients on their own – comanaging them instead with subspecialists – they will be involved in the ordering and monitoring of safety labs and other tests.

General practitioners “need to know side effects because they are going to deal with side effects when someone calls them in the middle of the night,” said Dr. Beales, who also is chief executive officer of Axovia Therapeutics, a biotech company developing gene therapies.

Some of the side effects that come with gene therapy are established. Adeno-associated virus (AAV) or AAV-mediated gene therapies carry an increased risk for damage to the heart and liver, Dr. Nelson said. Other side effects are less well known and could be specific to the treatment and the tissue it targets. Primary care will be critical in detecting these unexpected side effects and expediting visits with subspecialists, he said.

In rural Wyoming, pediatricians and family doctors are especially important, Ms. Gibbons said. In the 30-90 days after gene therapy, patients need a lot of follow-up for safety reasons.

But aftercare for gene therapy will be more than just monitoring and managing side effects. The diseases themselves will change. Patients will be living with conditions that once were lethal.

In some cases, gene therapy may largely eliminate the disease. The data suggest that thalassemia, for example, can be largely cured for decades with one infusion of a patient’s genetically modified hematopoietic stem cells made using bluebird bio’s Zynteglo, according to Christy Duncan, MD, medical director of clinical research at the gene therapy program at Boston Children’s Hospital.

But other gene therapies, like the one for DMD, will offer a “spectrum of benefits,” Dr. Nelson said. They will be lifesaving, but the signs of the disease will linger. Clinicians will be learning alongside specialists what the new disease state for DMD and other rare diseases looks like after gene therapy.

“As we get hundreds of such therapies, [post–gene therapy] will amount to a substantial part of the pediatric population,” Dr. Nelson said.
 

Finding patients

Many of these rare diseases that plague young patients are unmistakable. Children with moderate or severe dystrophic epidermolysis bullosa, for instance, carry a mutation that prevents them from making type VII collagen. The babies suffer wounds and excessive bleeding and tend to receive a quick diagnosis within the first 6 months of life, according to Andy Orth, chief commercial officer at Krystal Bio, manufacturer of a new wound-healing gene therapy, Vyjuvek, for the disorder.

Other rare neurologic or muscular diseases can go undiagnosed for years. Until recently, drug companies and researchers have had little motivation to speed up the timeline because early diagnosis of a disease like DMD would not change the outcome, Dr. Nelson said.

But with gene therapy, prognoses are changing. And finding diseases early could soon mean preserving muscular function or preventing neurologic damage, Dr. Duncan said.

Newborn sequencing “is not standard of care yet, but it’s certainly coming,” Josh Peterson, MD, MPH, director of the center for precision medicine at Vanderbilt University Medical Center, in Nashville, Tenn., told this news organization.

A recent survey of 238 specialists in rare diseases found that roughly 90% believe whole-genome sequencing should be available to all newborns. And 80% of those experts endorse 42 genes as disease predictors. Screening for rare diseases at birth could reveal a host of conditions in the first week of life and expedite treatment. But this strategy will often rely on primary care and pediatricians interpreting the results.

Most pediatricians think sequencing is a great idea, but they do not feel comfortable doing it themselves, Dr. Peterson said. The good news, he said, is that manufacturers have made screening tests straightforward. Some drug companies even offer free screenings for gene therapy candidates.

Dr. Peterson predicts pediatricians will need to be equipped to deliver negative results on their own, which will be the case for around 97%-99% of patients. They also will need to be clear on whether a negative result is definitive or if more testing is warranted.

Positive results are more nuanced. Genetic counseling is the ideal resource when delivering this kind of news to patients, but counselors are a scarce resource nationally – and particularly in rural areas, Dr. Nelson said. Physicians likely will have to rely on their own counseling training to some degree.

“I feel very strongly that genetic counselors are in short supply,” Ms. Gibbons in Colorado said. Patients need a friendly resource who can talk them through the disease and how it works. And that discussion is not a one-off, she said.

The number of board-certified genetic counselors in the United States has doubled to more than 6,000 in the past 10 years – a pace that is expected to continue, according to the National Society of Genetic Counselors. “However, the geographical distribution of genetic counselors is most concentrated in urban centers.”

Equally important to the counseling experience, according to Dr. Duncan at Boston Children’s, is a primary care physician’s network of connections. The best newborn screening rollouts across the country have succeeded because clinicians knew where to send people next and how to get families the help they needed, she said.

But she also cautioned that this learning curve will soon be overwhelming. As gene therapy expands, it may be difficult for primary care doctors to keep up with the science, treatment studies, and commercially available therapies. “It’s asking too much,” Dr. Duncan said.

The structure of primary care already stretches practitioners thin and will “affect how well precision medicine can be adopted and disseminated,” Dr. Peterson said. “I think that is a key issue.”

Artificial intelligence may offer a partial solution. Some genetic counseling models already exist, but their utility for clinicians so far is limited, Dr. Beales said. But he said he expects these tools to improve rapidly to help clinicians and patients. On the patient’s end, they may be able to answer questions and supplement basic genetic counseling. On the physician’s end, algorithms could help triage patients and help move them along to the next steps in the care pathway for these rare diseases.
 

The whole patient

Primary care physicians will not be expected to be experts in gene therapy or solely in charge of patient safety. They will have support from industry and subspecialists leading the development of these treatments, experts agreed.

But generalists should expect to be drawn into multidisciplinary care teams, be the sounding boards for patients making decisions about gene therapy, help arrange insurance coverage, and be the recipients of late-night phone calls about side effects.

All that, while never losing sight of the child’s holistic health. In children so sick, specialists, subspecialists, and even parents tend to focus only on the rare disease. The team can “get distracted from good normal routine care,” Dr. Nelson said. But these children aren’t exempt from check-ups, vaccine regimens, or the other diseases of childhood.

“In a world where we mitigate that core disease,” he said, “we need a partner in the general pediatrics community” investing in their long-term health.

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

In Colorado and Wyoming, nearly every baby born since 2020 is tested for signs of a mutation in the SMN1 gene, an indicator of spinal muscular atrophy (SMA). And in 4 years, genetic counselor Melissa Gibbons has seen 24 positive results. She has prepped 24 different pediatricians and family doctors to deliver the news: A seemingly perfect newborn likely has a lethal genetic disease.

Most of these clinicians had never cared for a child with SMA before, nor did they know that lifesaving gene therapy for the condition now exists. Still, the physicians were foundational to getting babies emergency treatment and monitoring the child’s safety after the fact.

“They are boots on the ground for this kind of [work],” Ms. Gibbons, who is the newborn screen coordinator for SMA in both states, told this news organization. “I’m not even sure they realize it.” As of today, the U.S. Food and Drug Administration has approved 16 gene therapies for the treatment of rare and debilitating diseases once considered lethal, such as SMA and cerebral adrenoleukodystrophy.

The newest addition to the list of approvals is Elevidys, Sarepta’s gene therapy for Duchenne muscular dystrophy (DMD). These conditions can now be mitigated, abated for years at a time, and even cured using treatments that tweak a patient’s DNA or RNA.

Hundreds of treatments are under development using the same mechanism. Viruses, liposomes, and other vectors of all kinds are being used to usher new genes into cells, correcting faulty copies or equipping a cell to fight disease. Cells gain the ability to make lifesaving proteins – proteins that heal wounds, restore muscle function, and fight cancer.

Within the decade, a significant fraction of the pediatric population will have gone through gene therapy, experts told this news organization. And primary care stands to be a linchpin in the scale-up of this kind of precision genetic medicine. Pediatricians and general practitioners will be central to finding and monitoring the patients that need these treatments. But the time and support doctors will need to fill that role remain scarce.

“This is a world we are creating right now, quite literally,” said Stanley Nelson, MD, director of the center for Duchenne muscular dystrophy at the University of California, Los Angeles. These cases – some before gene therapy and some after – will show up in primary care offices before the textbook is written.
 

Unknown side effects, new diseases

Even now, gene therapy is sequestered away in large academic medical research centers. The diagnosis, decision-making, and aftercare are handled by subspecialists working on clinical trials. While the research is ongoing, trial sponsors are keeping a close eye on enrolled patients. But that’s only until these drugs get market approval, Phil Beales, MD, chief medical officer at Congenica, a digital health company specializing in genome analysis support, said. Afterward, “the trialists will no longer have a role in looking after those patients.”

At that point, the role of primary care clinicians will be critically important. Although they probably will not manage gene-therapy patients on their own – comanaging them instead with subspecialists – they will be involved in the ordering and monitoring of safety labs and other tests.

General practitioners “need to know side effects because they are going to deal with side effects when someone calls them in the middle of the night,” said Dr. Beales, who also is chief executive officer of Axovia Therapeutics, a biotech company developing gene therapies.

Some of the side effects that come with gene therapy are established. Adeno-associated virus (AAV) or AAV-mediated gene therapies carry an increased risk for damage to the heart and liver, Dr. Nelson said. Other side effects are less well known and could be specific to the treatment and the tissue it targets. Primary care will be critical in detecting these unexpected side effects and expediting visits with subspecialists, he said.

In rural Wyoming, pediatricians and family doctors are especially important, Ms. Gibbons said. In the 30-90 days after gene therapy, patients need a lot of follow-up for safety reasons.

But aftercare for gene therapy will be more than just monitoring and managing side effects. The diseases themselves will change. Patients will be living with conditions that once were lethal.

In some cases, gene therapy may largely eliminate the disease. The data suggest that thalassemia, for example, can be largely cured for decades with one infusion of a patient’s genetically modified hematopoietic stem cells made using bluebird bio’s Zynteglo, according to Christy Duncan, MD, medical director of clinical research at the gene therapy program at Boston Children’s Hospital.

But other gene therapies, like the one for DMD, will offer a “spectrum of benefits,” Dr. Nelson said. They will be lifesaving, but the signs of the disease will linger. Clinicians will be learning alongside specialists what the new disease state for DMD and other rare diseases looks like after gene therapy.

“As we get hundreds of such therapies, [post–gene therapy] will amount to a substantial part of the pediatric population,” Dr. Nelson said.
 

Finding patients

Many of these rare diseases that plague young patients are unmistakable. Children with moderate or severe dystrophic epidermolysis bullosa, for instance, carry a mutation that prevents them from making type VII collagen. The babies suffer wounds and excessive bleeding and tend to receive a quick diagnosis within the first 6 months of life, according to Andy Orth, chief commercial officer at Krystal Bio, manufacturer of a new wound-healing gene therapy, Vyjuvek, for the disorder.

Other rare neurologic or muscular diseases can go undiagnosed for years. Until recently, drug companies and researchers have had little motivation to speed up the timeline because early diagnosis of a disease like DMD would not change the outcome, Dr. Nelson said.

But with gene therapy, prognoses are changing. And finding diseases early could soon mean preserving muscular function or preventing neurologic damage, Dr. Duncan said.

Newborn sequencing “is not standard of care yet, but it’s certainly coming,” Josh Peterson, MD, MPH, director of the center for precision medicine at Vanderbilt University Medical Center, in Nashville, Tenn., told this news organization.

A recent survey of 238 specialists in rare diseases found that roughly 90% believe whole-genome sequencing should be available to all newborns. And 80% of those experts endorse 42 genes as disease predictors. Screening for rare diseases at birth could reveal a host of conditions in the first week of life and expedite treatment. But this strategy will often rely on primary care and pediatricians interpreting the results.

Most pediatricians think sequencing is a great idea, but they do not feel comfortable doing it themselves, Dr. Peterson said. The good news, he said, is that manufacturers have made screening tests straightforward. Some drug companies even offer free screenings for gene therapy candidates.

Dr. Peterson predicts pediatricians will need to be equipped to deliver negative results on their own, which will be the case for around 97%-99% of patients. They also will need to be clear on whether a negative result is definitive or if more testing is warranted.

Positive results are more nuanced. Genetic counseling is the ideal resource when delivering this kind of news to patients, but counselors are a scarce resource nationally – and particularly in rural areas, Dr. Nelson said. Physicians likely will have to rely on their own counseling training to some degree.

“I feel very strongly that genetic counselors are in short supply,” Ms. Gibbons in Colorado said. Patients need a friendly resource who can talk them through the disease and how it works. And that discussion is not a one-off, she said.

The number of board-certified genetic counselors in the United States has doubled to more than 6,000 in the past 10 years – a pace that is expected to continue, according to the National Society of Genetic Counselors. “However, the geographical distribution of genetic counselors is most concentrated in urban centers.”

Equally important to the counseling experience, according to Dr. Duncan at Boston Children’s, is a primary care physician’s network of connections. The best newborn screening rollouts across the country have succeeded because clinicians knew where to send people next and how to get families the help they needed, she said.

But she also cautioned that this learning curve will soon be overwhelming. As gene therapy expands, it may be difficult for primary care doctors to keep up with the science, treatment studies, and commercially available therapies. “It’s asking too much,” Dr. Duncan said.

The structure of primary care already stretches practitioners thin and will “affect how well precision medicine can be adopted and disseminated,” Dr. Peterson said. “I think that is a key issue.”

Artificial intelligence may offer a partial solution. Some genetic counseling models already exist, but their utility for clinicians so far is limited, Dr. Beales said. But he said he expects these tools to improve rapidly to help clinicians and patients. On the patient’s end, they may be able to answer questions and supplement basic genetic counseling. On the physician’s end, algorithms could help triage patients and help move them along to the next steps in the care pathway for these rare diseases.
 

The whole patient

Primary care physicians will not be expected to be experts in gene therapy or solely in charge of patient safety. They will have support from industry and subspecialists leading the development of these treatments, experts agreed.

But generalists should expect to be drawn into multidisciplinary care teams, be the sounding boards for patients making decisions about gene therapy, help arrange insurance coverage, and be the recipients of late-night phone calls about side effects.

All that, while never losing sight of the child’s holistic health. In children so sick, specialists, subspecialists, and even parents tend to focus only on the rare disease. The team can “get distracted from good normal routine care,” Dr. Nelson said. But these children aren’t exempt from check-ups, vaccine regimens, or the other diseases of childhood.

“In a world where we mitigate that core disease,” he said, “we need a partner in the general pediatrics community” investing in their long-term health.

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

In Colorado and Wyoming, nearly every baby born since 2020 is tested for signs of a mutation in the SMN1 gene, an indicator of spinal muscular atrophy (SMA). And in 4 years, genetic counselor Melissa Gibbons has seen 24 positive results. She has prepped 24 different pediatricians and family doctors to deliver the news: A seemingly perfect newborn likely has a lethal genetic disease.

Most of these clinicians had never cared for a child with SMA before, nor did they know that lifesaving gene therapy for the condition now exists. Still, the physicians were foundational to getting babies emergency treatment and monitoring the child’s safety after the fact.

“They are boots on the ground for this kind of [work],” Ms. Gibbons, who is the newborn screen coordinator for SMA in both states, told this news organization. “I’m not even sure they realize it.” As of today, the U.S. Food and Drug Administration has approved 16 gene therapies for the treatment of rare and debilitating diseases once considered lethal, such as SMA and cerebral adrenoleukodystrophy.

The newest addition to the list of approvals is Elevidys, Sarepta’s gene therapy for Duchenne muscular dystrophy (DMD). These conditions can now be mitigated, abated for years at a time, and even cured using treatments that tweak a patient’s DNA or RNA.

Hundreds of treatments are under development using the same mechanism. Viruses, liposomes, and other vectors of all kinds are being used to usher new genes into cells, correcting faulty copies or equipping a cell to fight disease. Cells gain the ability to make lifesaving proteins – proteins that heal wounds, restore muscle function, and fight cancer.

Within the decade, a significant fraction of the pediatric population will have gone through gene therapy, experts told this news organization. And primary care stands to be a linchpin in the scale-up of this kind of precision genetic medicine. Pediatricians and general practitioners will be central to finding and monitoring the patients that need these treatments. But the time and support doctors will need to fill that role remain scarce.

“This is a world we are creating right now, quite literally,” said Stanley Nelson, MD, director of the center for Duchenne muscular dystrophy at the University of California, Los Angeles. These cases – some before gene therapy and some after – will show up in primary care offices before the textbook is written.
 

Unknown side effects, new diseases

Even now, gene therapy is sequestered away in large academic medical research centers. The diagnosis, decision-making, and aftercare are handled by subspecialists working on clinical trials. While the research is ongoing, trial sponsors are keeping a close eye on enrolled patients. But that’s only until these drugs get market approval, Phil Beales, MD, chief medical officer at Congenica, a digital health company specializing in genome analysis support, said. Afterward, “the trialists will no longer have a role in looking after those patients.”

At that point, the role of primary care clinicians will be critically important. Although they probably will not manage gene-therapy patients on their own – comanaging them instead with subspecialists – they will be involved in the ordering and monitoring of safety labs and other tests.

General practitioners “need to know side effects because they are going to deal with side effects when someone calls them in the middle of the night,” said Dr. Beales, who also is chief executive officer of Axovia Therapeutics, a biotech company developing gene therapies.

Some of the side effects that come with gene therapy are established. Adeno-associated virus (AAV) or AAV-mediated gene therapies carry an increased risk for damage to the heart and liver, Dr. Nelson said. Other side effects are less well known and could be specific to the treatment and the tissue it targets. Primary care will be critical in detecting these unexpected side effects and expediting visits with subspecialists, he said.

In rural Wyoming, pediatricians and family doctors are especially important, Ms. Gibbons said. In the 30-90 days after gene therapy, patients need a lot of follow-up for safety reasons.

But aftercare for gene therapy will be more than just monitoring and managing side effects. The diseases themselves will change. Patients will be living with conditions that once were lethal.

In some cases, gene therapy may largely eliminate the disease. The data suggest that thalassemia, for example, can be largely cured for decades with one infusion of a patient’s genetically modified hematopoietic stem cells made using bluebird bio’s Zynteglo, according to Christy Duncan, MD, medical director of clinical research at the gene therapy program at Boston Children’s Hospital.

But other gene therapies, like the one for DMD, will offer a “spectrum of benefits,” Dr. Nelson said. They will be lifesaving, but the signs of the disease will linger. Clinicians will be learning alongside specialists what the new disease state for DMD and other rare diseases looks like after gene therapy.

“As we get hundreds of such therapies, [post–gene therapy] will amount to a substantial part of the pediatric population,” Dr. Nelson said.
 

Finding patients

Many of these rare diseases that plague young patients are unmistakable. Children with moderate or severe dystrophic epidermolysis bullosa, for instance, carry a mutation that prevents them from making type VII collagen. The babies suffer wounds and excessive bleeding and tend to receive a quick diagnosis within the first 6 months of life, according to Andy Orth, chief commercial officer at Krystal Bio, manufacturer of a new wound-healing gene therapy, Vyjuvek, for the disorder.

Other rare neurologic or muscular diseases can go undiagnosed for years. Until recently, drug companies and researchers have had little motivation to speed up the timeline because early diagnosis of a disease like DMD would not change the outcome, Dr. Nelson said.

But with gene therapy, prognoses are changing. And finding diseases early could soon mean preserving muscular function or preventing neurologic damage, Dr. Duncan said.

Newborn sequencing “is not standard of care yet, but it’s certainly coming,” Josh Peterson, MD, MPH, director of the center for precision medicine at Vanderbilt University Medical Center, in Nashville, Tenn., told this news organization.

A recent survey of 238 specialists in rare diseases found that roughly 90% believe whole-genome sequencing should be available to all newborns. And 80% of those experts endorse 42 genes as disease predictors. Screening for rare diseases at birth could reveal a host of conditions in the first week of life and expedite treatment. But this strategy will often rely on primary care and pediatricians interpreting the results.

Most pediatricians think sequencing is a great idea, but they do not feel comfortable doing it themselves, Dr. Peterson said. The good news, he said, is that manufacturers have made screening tests straightforward. Some drug companies even offer free screenings for gene therapy candidates.

Dr. Peterson predicts pediatricians will need to be equipped to deliver negative results on their own, which will be the case for around 97%-99% of patients. They also will need to be clear on whether a negative result is definitive or if more testing is warranted.

Positive results are more nuanced. Genetic counseling is the ideal resource when delivering this kind of news to patients, but counselors are a scarce resource nationally – and particularly in rural areas, Dr. Nelson said. Physicians likely will have to rely on their own counseling training to some degree.

“I feel very strongly that genetic counselors are in short supply,” Ms. Gibbons in Colorado said. Patients need a friendly resource who can talk them through the disease and how it works. And that discussion is not a one-off, she said.

The number of board-certified genetic counselors in the United States has doubled to more than 6,000 in the past 10 years – a pace that is expected to continue, according to the National Society of Genetic Counselors. “However, the geographical distribution of genetic counselors is most concentrated in urban centers.”

Equally important to the counseling experience, according to Dr. Duncan at Boston Children’s, is a primary care physician’s network of connections. The best newborn screening rollouts across the country have succeeded because clinicians knew where to send people next and how to get families the help they needed, she said.

But she also cautioned that this learning curve will soon be overwhelming. As gene therapy expands, it may be difficult for primary care doctors to keep up with the science, treatment studies, and commercially available therapies. “It’s asking too much,” Dr. Duncan said.

The structure of primary care already stretches practitioners thin and will “affect how well precision medicine can be adopted and disseminated,” Dr. Peterson said. “I think that is a key issue.”

Artificial intelligence may offer a partial solution. Some genetic counseling models already exist, but their utility for clinicians so far is limited, Dr. Beales said. But he said he expects these tools to improve rapidly to help clinicians and patients. On the patient’s end, they may be able to answer questions and supplement basic genetic counseling. On the physician’s end, algorithms could help triage patients and help move them along to the next steps in the care pathway for these rare diseases.
 

The whole patient

Primary care physicians will not be expected to be experts in gene therapy or solely in charge of patient safety. They will have support from industry and subspecialists leading the development of these treatments, experts agreed.

But generalists should expect to be drawn into multidisciplinary care teams, be the sounding boards for patients making decisions about gene therapy, help arrange insurance coverage, and be the recipients of late-night phone calls about side effects.

All that, while never losing sight of the child’s holistic health. In children so sick, specialists, subspecialists, and even parents tend to focus only on the rare disease. The team can “get distracted from good normal routine care,” Dr. Nelson said. But these children aren’t exempt from check-ups, vaccine regimens, or the other diseases of childhood.

“In a world where we mitigate that core disease,” he said, “we need a partner in the general pediatrics community” investing in their long-term health.

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

The U.S. Preventive Services Task Force has again determined that current evidence is insufficient to recommend screening for lipid disorders among asymptomatic children and patients aged 20 years or younger.

The group’s final recommendation and corresponding evidence report were published  in the Journal of the American Medical Association, following a draft recommendation in January.

The organization reached a similar conclusion following its evaluation in 2016.

“There’s just not enough evidence to determine whether or not screening all children for high cholesterol improves their heart health into adulthood,” said Katrina Donahue, MD, MPH, a USPSTF member and a professor in the department of family medicine at the University of North Carolina at Chapel Hill. “We’re calling for additional research on the effectiveness of screening for and treatment of high cholesterol in children and adolescents to prevent heart attacks, strokes, and death in adulthood.”

The task force recommended other evidence-based strategies to promote heart health, such as screening for obesity and interventions to prevent tobacco use.

The recommendation was the result of a review of 43 studies from MEDLINE and the Cochrane Central Register of Controlled Trials through May 16, 2022. No randomized controlled trial directly addressed the effectiveness or harms of lipid screening for children and adolescents. The task force continued to use article alerts and targeted journal searches through March 24, 2023.

Conditions such as familial hypercholesterolemia and multifactorial dyslipidemia can cause abnormally high lipid levels in children, potentially leading to premature cardiovascular events such as myocardial infarction, stroke, and death in adulthood. According to the USPSTF, the prevalence of FH in U.S. children and adolescents ranges from 0.2% to 0.4% (one in every 250-500 youth). Multifactorial dyslipidemia is more common – the prevalence in children and adolescents ranges from 7.1% to 9.4%.

In an editorial response to the task force’s statement, the authors, including Sarah D. de Ferranti, MD, department of pediatrics at Harvard Medical School, Boston, question the impact of not screening children to identify FH and other conditions and caution against the subsequent delay in treatment.

“Treating FH during childhood slows the progression of vascular finding in atherosclerosis,” the authors write.

They note that the recommendation “leaves a void for clinicians seeking to provide care for patients today” while additional research is conducted.

Sarah Nosal, MD, a member of the board of directors of the American Academy of Family Physicians, said that despite the lack of a recommendation, primary care clinicians can still encourage proper nutrition and physical activity for patients.

Dr. Nosal said that even without clear recommendations from the USPSTF, in the rare case of a patient with a family history of FH, she would order a lipid test and discuss treatment plans with the patient and family, if needed.

“We really don’t want to do tests that we don’t know what to do with the information,” she said.

One USPSTF member reported receiving grants from Healthwise, a nonprofit organization, outside the submitted work.

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

The U.S. Preventive Services Task Force has again determined that current evidence is insufficient to recommend screening for lipid disorders among asymptomatic children and patients aged 20 years or younger.

The group’s final recommendation and corresponding evidence report were published  in the Journal of the American Medical Association, following a draft recommendation in January.

The organization reached a similar conclusion following its evaluation in 2016.

“There’s just not enough evidence to determine whether or not screening all children for high cholesterol improves their heart health into adulthood,” said Katrina Donahue, MD, MPH, a USPSTF member and a professor in the department of family medicine at the University of North Carolina at Chapel Hill. “We’re calling for additional research on the effectiveness of screening for and treatment of high cholesterol in children and adolescents to prevent heart attacks, strokes, and death in adulthood.”

The task force recommended other evidence-based strategies to promote heart health, such as screening for obesity and interventions to prevent tobacco use.

The recommendation was the result of a review of 43 studies from MEDLINE and the Cochrane Central Register of Controlled Trials through May 16, 2022. No randomized controlled trial directly addressed the effectiveness or harms of lipid screening for children and adolescents. The task force continued to use article alerts and targeted journal searches through March 24, 2023.

Conditions such as familial hypercholesterolemia and multifactorial dyslipidemia can cause abnormally high lipid levels in children, potentially leading to premature cardiovascular events such as myocardial infarction, stroke, and death in adulthood. According to the USPSTF, the prevalence of FH in U.S. children and adolescents ranges from 0.2% to 0.4% (one in every 250-500 youth). Multifactorial dyslipidemia is more common – the prevalence in children and adolescents ranges from 7.1% to 9.4%.

In an editorial response to the task force’s statement, the authors, including Sarah D. de Ferranti, MD, department of pediatrics at Harvard Medical School, Boston, question the impact of not screening children to identify FH and other conditions and caution against the subsequent delay in treatment.

“Treating FH during childhood slows the progression of vascular finding in atherosclerosis,” the authors write.

They note that the recommendation “leaves a void for clinicians seeking to provide care for patients today” while additional research is conducted.

Sarah Nosal, MD, a member of the board of directors of the American Academy of Family Physicians, said that despite the lack of a recommendation, primary care clinicians can still encourage proper nutrition and physical activity for patients.

Dr. Nosal said that even without clear recommendations from the USPSTF, in the rare case of a patient with a family history of FH, she would order a lipid test and discuss treatment plans with the patient and family, if needed.

“We really don’t want to do tests that we don’t know what to do with the information,” she said.

One USPSTF member reported receiving grants from Healthwise, a nonprofit organization, outside the submitted work.

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

The U.S. Preventive Services Task Force has again determined that current evidence is insufficient to recommend screening for lipid disorders among asymptomatic children and patients aged 20 years or younger.

The group’s final recommendation and corresponding evidence report were published  in the Journal of the American Medical Association, following a draft recommendation in January.

The organization reached a similar conclusion following its evaluation in 2016.

“There’s just not enough evidence to determine whether or not screening all children for high cholesterol improves their heart health into adulthood,” said Katrina Donahue, MD, MPH, a USPSTF member and a professor in the department of family medicine at the University of North Carolina at Chapel Hill. “We’re calling for additional research on the effectiveness of screening for and treatment of high cholesterol in children and adolescents to prevent heart attacks, strokes, and death in adulthood.”

The task force recommended other evidence-based strategies to promote heart health, such as screening for obesity and interventions to prevent tobacco use.

The recommendation was the result of a review of 43 studies from MEDLINE and the Cochrane Central Register of Controlled Trials through May 16, 2022. No randomized controlled trial directly addressed the effectiveness or harms of lipid screening for children and adolescents. The task force continued to use article alerts and targeted journal searches through March 24, 2023.

Conditions such as familial hypercholesterolemia and multifactorial dyslipidemia can cause abnormally high lipid levels in children, potentially leading to premature cardiovascular events such as myocardial infarction, stroke, and death in adulthood. According to the USPSTF, the prevalence of FH in U.S. children and adolescents ranges from 0.2% to 0.4% (one in every 250-500 youth). Multifactorial dyslipidemia is more common – the prevalence in children and adolescents ranges from 7.1% to 9.4%.

In an editorial response to the task force’s statement, the authors, including Sarah D. de Ferranti, MD, department of pediatrics at Harvard Medical School, Boston, question the impact of not screening children to identify FH and other conditions and caution against the subsequent delay in treatment.

“Treating FH during childhood slows the progression of vascular finding in atherosclerosis,” the authors write.

They note that the recommendation “leaves a void for clinicians seeking to provide care for patients today” while additional research is conducted.

Sarah Nosal, MD, a member of the board of directors of the American Academy of Family Physicians, said that despite the lack of a recommendation, primary care clinicians can still encourage proper nutrition and physical activity for patients.

Dr. Nosal said that even without clear recommendations from the USPSTF, in the rare case of a patient with a family history of FH, she would order a lipid test and discuss treatment plans with the patient and family, if needed.

“We really don’t want to do tests that we don’t know what to do with the information,” she said.

One USPSTF member reported receiving grants from Healthwise, a nonprofit organization, outside the submitted work.

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

Are there medical conditions other than obesity where physicians, if even inadvertently, regularly sabotage their patients’ efforts at managing them? Because for patients with obesity, their physicians, sometimes even before they walk into the examining room to meet them, do and say things that may quash their weight loss efforts.

No doubt this list will be nonexhaustive, but here are what I see as the top 10 ways doctors sabotage their patients’ weight loss journeys.

• 1. Having an office that is anxiety provoking, exclusionary, and/or fat phobic for people with obesity, which in turn may remove trust and preclude conversation. Examples of this would be offices without chairs in the waiting room that are suitable for people with obesity; with reading materials such as glossy magazines like Men’s Health and Shape, glorifying unhealthy dieting and body ideals; or where the scale is in a nonprivate area or has a very narrow platform, or maxes out at a weight lower than many patients’.
• 2. Not taking an actual history. Meaning, physicians regularly launch into a “you should really lose weight” speech without exploring a patient’s history of weight loss and social determinants of health. In some cases, that patient may have a history of disordered eating or body dysmorphia, and then this discussion needs to be approached carefully with those facts underwriting its tenor and direction. In other cases, patients’ social determinants of health would make intentional behavior change efforts in the name of weight management an impossible luxury. And sometimes that same patient may in fact be maintaining a clinically meaningful weight loss from their peak weight already. In all cases, not speaking with your patients and instead speaking at your patients will not increase their likelihood to trust or follow or seek your advice.
• 3. Pushing useless diet advice. The most common and most useless are some variation on needing to just eat less and move more. That’s about as useful as telling someone that making money requires them to buy low and sell high. Or telling someone with depression that they should just cheer up and look at the bright side of things.
• 4. Pushing specific diet advice (intermittent fasting, keto, low carb, vegan, low fat, whatever) as if it’s the only way or the best way to lose weight. The research is clear: There is no one best dietary approach, and one person’s best diet is another person’s worst. Yet, some clinicians are themselves diet zealots and preach one diet over all others. Of course, many of their patients may well have already tried that approach, while others won’t enjoy it, and so promoting it above all others will fail a great many people.
• 5. Refusing to prescribe medications to patients who meet the clinical criteria for use, especially now that there are truly effective and useful medications. Do these same clinicians refuse to prescribe antihypertensives or oral hypoglycemics to patients whose blood pressures or blood sugars are risking their health? Related would be those clinicians who don’t bother to learn enough about pharmaceutical options for obesity to feel comfortable prescribing them. This, despite the fact that statistically, well over 30% of their patients have obesity, and polls suggest that at least half of those embark on weight loss efforts annually. If a patient meets clinical criteria for a medication’s approved indication and a doctor won’t prescribe it because of their personal beliefs, in my opinion that’s grounds for a regulatory complaint.
• 6. Fearmongering around medications regarding adverse or unknown effects. The media’s coverage of new antiobesity medications is alarmist, to say the least, and for reasons I can’t fathom, given how well tolerated these medications are when dose titration is slow, monitored, and adjusted appropriately. Many physicians are not only buying into media narratives but are also spreading them.
• 7. Stopping medications for obesity when weight is lost. Do you also stop blood pressure medications when they normalize a patient’s blood pressure? Chronic conditions require ongoing long-term treatment. And yet I hear about this in my practice regularly.
• 8. Prescribing medications that cause weight gain rather than alternatives that don’t, or without discussion of same, or without the concomitant prescription of medication to counter it. From atypical antipsychotics to antidepressants to certain antiseizure medications to some blood pressure medications, there are those that have been shown to lead to, at times, dramatic weight gain. Yet, physicians will still regularly prescribe them to patients with obesity without first trying patients on available alternatives that don’t lead to weight gain, or without at least monitoring and then considering the prescription of an antiobesity medication to try to mitigate iatrogenic gain.
• 9. Setting ridiculous and unrealistic weight loss goals with patients. Without medication, the average person may lose 10% of their weight with purely behavioral efforts, 15%-20% with the addition of medications to those behavioral efforts, and 30% with the addition of bariatric surgery to their behavioral efforts. So why do so many physicians suggest goals that greatly exceed those averages? Imagine being committed to learning to run and having your running coach tell you at your training outset that your goal is to run a marathon within a Boston Marathon qualifying time. The goal should be whatever weight a person reaches living the healthiest life that they can honestly enjoy, not the Boston Marathon of weight loss.
• 10. Not discussing all options with all patients. Yes, food and fitness levers can affect weight, but that doesn’t mean that patients who meet the medical criteria for antiobesity medication or bariatric surgery shouldn’t be informed of their options. Our job as physicians is to fully inform our patients about the risks and benefits of all treatment options and then to support our patients’ decisions as to what option they want to pursue (including none, by the way). Our job is not to exclude discussion of proven and available options because our weight biases see us personally not believing in them – or worse, thinking that patients haven’t tried food and fitness umpteen times before, and that we require them to fail those efforts yet again before we stop gatekeeping their access to effective adjunctive therapeutic interventions.

Until recently, underwriting weight bias in medicine has been the dearth of effective treatments which in turn probably contributed to the overall lack of education for physicians in obesity management despite its extremely high prevalence. The times, though, are definitely a-changin’. Consequent to these new generations of medications rapidly coming online, by necessity we will see improvements in medical education around obesity management. Meanwhile, their efficacy will help dispel the bias that underlies much of this list. A decade or 2 from now, we will see obesity treated as we do every other chronic noncommunicable disease with lifestyle levers – with patient-centered care free from judgment and blame, and with a myriad of therapeutic options that physicians objectively, not subjectively, inform and prescribe to their patients.

Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health and Novo Nordisk.
 

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

Are there medical conditions other than obesity where physicians, if even inadvertently, regularly sabotage their patients’ efforts at managing them? Because for patients with obesity, their physicians, sometimes even before they walk into the examining room to meet them, do and say things that may quash their weight loss efforts.

No doubt this list will be nonexhaustive, but here are what I see as the top 10 ways doctors sabotage their patients’ weight loss journeys.

• 1. Having an office that is anxiety provoking, exclusionary, and/or fat phobic for people with obesity, which in turn may remove trust and preclude conversation. Examples of this would be offices without chairs in the waiting room that are suitable for people with obesity; with reading materials such as glossy magazines like Men’s Health and Shape, glorifying unhealthy dieting and body ideals; or where the scale is in a nonprivate area or has a very narrow platform, or maxes out at a weight lower than many patients’.
• 2. Not taking an actual history. Meaning, physicians regularly launch into a “you should really lose weight” speech without exploring a patient’s history of weight loss and social determinants of health. In some cases, that patient may have a history of disordered eating or body dysmorphia, and then this discussion needs to be approached carefully with those facts underwriting its tenor and direction. In other cases, patients’ social determinants of health would make intentional behavior change efforts in the name of weight management an impossible luxury. And sometimes that same patient may in fact be maintaining a clinically meaningful weight loss from their peak weight already. In all cases, not speaking with your patients and instead speaking at your patients will not increase their likelihood to trust or follow or seek your advice.
• 3. Pushing useless diet advice. The most common and most useless are some variation on needing to just eat less and move more. That’s about as useful as telling someone that making money requires them to buy low and sell high. Or telling someone with depression that they should just cheer up and look at the bright side of things.
• 4. Pushing specific diet advice (intermittent fasting, keto, low carb, vegan, low fat, whatever) as if it’s the only way or the best way to lose weight. The research is clear: There is no one best dietary approach, and one person’s best diet is another person’s worst. Yet, some clinicians are themselves diet zealots and preach one diet over all others. Of course, many of their patients may well have already tried that approach, while others won’t enjoy it, and so promoting it above all others will fail a great many people.
• 5. Refusing to prescribe medications to patients who meet the clinical criteria for use, especially now that there are truly effective and useful medications. Do these same clinicians refuse to prescribe antihypertensives or oral hypoglycemics to patients whose blood pressures or blood sugars are risking their health? Related would be those clinicians who don’t bother to learn enough about pharmaceutical options for obesity to feel comfortable prescribing them. This, despite the fact that statistically, well over 30% of their patients have obesity, and polls suggest that at least half of those embark on weight loss efforts annually. If a patient meets clinical criteria for a medication’s approved indication and a doctor won’t prescribe it because of their personal beliefs, in my opinion that’s grounds for a regulatory complaint.
• 6. Fearmongering around medications regarding adverse or unknown effects. The media’s coverage of new antiobesity medications is alarmist, to say the least, and for reasons I can’t fathom, given how well tolerated these medications are when dose titration is slow, monitored, and adjusted appropriately. Many physicians are not only buying into media narratives but are also spreading them.
• 7. Stopping medications for obesity when weight is lost. Do you also stop blood pressure medications when they normalize a patient’s blood pressure? Chronic conditions require ongoing long-term treatment. And yet I hear about this in my practice regularly.
• 8. Prescribing medications that cause weight gain rather than alternatives that don’t, or without discussion of same, or without the concomitant prescription of medication to counter it. From atypical antipsychotics to antidepressants to certain antiseizure medications to some blood pressure medications, there are those that have been shown to lead to, at times, dramatic weight gain. Yet, physicians will still regularly prescribe them to patients with obesity without first trying patients on available alternatives that don’t lead to weight gain, or without at least monitoring and then considering the prescription of an antiobesity medication to try to mitigate iatrogenic gain.
• 9. Setting ridiculous and unrealistic weight loss goals with patients. Without medication, the average person may lose 10% of their weight with purely behavioral efforts, 15%-20% with the addition of medications to those behavioral efforts, and 30% with the addition of bariatric surgery to their behavioral efforts. So why do so many physicians suggest goals that greatly exceed those averages? Imagine being committed to learning to run and having your running coach tell you at your training outset that your goal is to run a marathon within a Boston Marathon qualifying time. The goal should be whatever weight a person reaches living the healthiest life that they can honestly enjoy, not the Boston Marathon of weight loss.
• 10. Not discussing all options with all patients. Yes, food and fitness levers can affect weight, but that doesn’t mean that patients who meet the medical criteria for antiobesity medication or bariatric surgery shouldn’t be informed of their options. Our job as physicians is to fully inform our patients about the risks and benefits of all treatment options and then to support our patients’ decisions as to what option they want to pursue (including none, by the way). Our job is not to exclude discussion of proven and available options because our weight biases see us personally not believing in them – or worse, thinking that patients haven’t tried food and fitness umpteen times before, and that we require them to fail those efforts yet again before we stop gatekeeping their access to effective adjunctive therapeutic interventions.

Until recently, underwriting weight bias in medicine has been the dearth of effective treatments which in turn probably contributed to the overall lack of education for physicians in obesity management despite its extremely high prevalence. The times, though, are definitely a-changin’. Consequent to these new generations of medications rapidly coming online, by necessity we will see improvements in medical education around obesity management. Meanwhile, their efficacy will help dispel the bias that underlies much of this list. A decade or 2 from now, we will see obesity treated as we do every other chronic noncommunicable disease with lifestyle levers – with patient-centered care free from judgment and blame, and with a myriad of therapeutic options that physicians objectively, not subjectively, inform and prescribe to their patients.

Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health and Novo Nordisk.
 

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

Are there medical conditions other than obesity where physicians, if even inadvertently, regularly sabotage their patients’ efforts at managing them? Because for patients with obesity, their physicians, sometimes even before they walk into the examining room to meet them, do and say things that may quash their weight loss efforts.

No doubt this list will be nonexhaustive, but here are what I see as the top 10 ways doctors sabotage their patients’ weight loss journeys.

• 1. Having an office that is anxiety provoking, exclusionary, and/or fat phobic for people with obesity, which in turn may remove trust and preclude conversation. Examples of this would be offices without chairs in the waiting room that are suitable for people with obesity; with reading materials such as glossy magazines like Men’s Health and Shape, glorifying unhealthy dieting and body ideals; or where the scale is in a nonprivate area or has a very narrow platform, or maxes out at a weight lower than many patients’.
• 2. Not taking an actual history. Meaning, physicians regularly launch into a “you should really lose weight” speech without exploring a patient’s history of weight loss and social determinants of health. In some cases, that patient may have a history of disordered eating or body dysmorphia, and then this discussion needs to be approached carefully with those facts underwriting its tenor and direction. In other cases, patients’ social determinants of health would make intentional behavior change efforts in the name of weight management an impossible luxury. And sometimes that same patient may in fact be maintaining a clinically meaningful weight loss from their peak weight already. In all cases, not speaking with your patients and instead speaking at your patients will not increase their likelihood to trust or follow or seek your advice.
• 3. Pushing useless diet advice. The most common and most useless are some variation on needing to just eat less and move more. That’s about as useful as telling someone that making money requires them to buy low and sell high. Or telling someone with depression that they should just cheer up and look at the bright side of things.
• 4. Pushing specific diet advice (intermittent fasting, keto, low carb, vegan, low fat, whatever) as if it’s the only way or the best way to lose weight. The research is clear: There is no one best dietary approach, and one person’s best diet is another person’s worst. Yet, some clinicians are themselves diet zealots and preach one diet over all others. Of course, many of their patients may well have already tried that approach, while others won’t enjoy it, and so promoting it above all others will fail a great many people.
• 5. Refusing to prescribe medications to patients who meet the clinical criteria for use, especially now that there are truly effective and useful medications. Do these same clinicians refuse to prescribe antihypertensives or oral hypoglycemics to patients whose blood pressures or blood sugars are risking their health? Related would be those clinicians who don’t bother to learn enough about pharmaceutical options for obesity to feel comfortable prescribing them. This, despite the fact that statistically, well over 30% of their patients have obesity, and polls suggest that at least half of those embark on weight loss efforts annually. If a patient meets clinical criteria for a medication’s approved indication and a doctor won’t prescribe it because of their personal beliefs, in my opinion that’s grounds for a regulatory complaint.
• 6. Fearmongering around medications regarding adverse or unknown effects. The media’s coverage of new antiobesity medications is alarmist, to say the least, and for reasons I can’t fathom, given how well tolerated these medications are when dose titration is slow, monitored, and adjusted appropriately. Many physicians are not only buying into media narratives but are also spreading them.
• 7. Stopping medications for obesity when weight is lost. Do you also stop blood pressure medications when they normalize a patient’s blood pressure? Chronic conditions require ongoing long-term treatment. And yet I hear about this in my practice regularly.
• 8. Prescribing medications that cause weight gain rather than alternatives that don’t, or without discussion of same, or without the concomitant prescription of medication to counter it. From atypical antipsychotics to antidepressants to certain antiseizure medications to some blood pressure medications, there are those that have been shown to lead to, at times, dramatic weight gain. Yet, physicians will still regularly prescribe them to patients with obesity without first trying patients on available alternatives that don’t lead to weight gain, or without at least monitoring and then considering the prescription of an antiobesity medication to try to mitigate iatrogenic gain.
• 9. Setting ridiculous and unrealistic weight loss goals with patients. Without medication, the average person may lose 10% of their weight with purely behavioral efforts, 15%-20% with the addition of medications to those behavioral efforts, and 30% with the addition of bariatric surgery to their behavioral efforts. So why do so many physicians suggest goals that greatly exceed those averages? Imagine being committed to learning to run and having your running coach tell you at your training outset that your goal is to run a marathon within a Boston Marathon qualifying time. The goal should be whatever weight a person reaches living the healthiest life that they can honestly enjoy, not the Boston Marathon of weight loss.
• 10. Not discussing all options with all patients. Yes, food and fitness levers can affect weight, but that doesn’t mean that patients who meet the medical criteria for antiobesity medication or bariatric surgery shouldn’t be informed of their options. Our job as physicians is to fully inform our patients about the risks and benefits of all treatment options and then to support our patients’ decisions as to what option they want to pursue (including none, by the way). Our job is not to exclude discussion of proven and available options because our weight biases see us personally not believing in them – or worse, thinking that patients haven’t tried food and fitness umpteen times before, and that we require them to fail those efforts yet again before we stop gatekeeping their access to effective adjunctive therapeutic interventions.

Until recently, underwriting weight bias in medicine has been the dearth of effective treatments which in turn probably contributed to the overall lack of education for physicians in obesity management despite its extremely high prevalence. The times, though, are definitely a-changin’. Consequent to these new generations of medications rapidly coming online, by necessity we will see improvements in medical education around obesity management. Meanwhile, their efficacy will help dispel the bias that underlies much of this list. A decade or 2 from now, we will see obesity treated as we do every other chronic noncommunicable disease with lifestyle levers – with patient-centered care free from judgment and blame, and with a myriad of therapeutic options that physicians objectively, not subjectively, inform and prescribe to their patients.

Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health and Novo Nordisk.
 

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

The incidence of type 1 diabetes has risen during the COVID-19 pandemic, according to a recent meta-analysis.

The review compared 2 years of data from during the pandemic to data from a prepandemic period, and showed a higher incidence of type 1 diabetes in the first year (incidence rate ratio, 1.14) and second year (IRR, 1.27) of the pandemic. The investigators also found an increase in the incidence of diabetic ketoacidosis (DKA) (IRR, 1.26).

The meta-analysis included 17 studies of 38,149 children and adolescents with newly diagnosed type 1 diabetes. “Putting them all together really gave us more confidence to say this is something that we think is real,” study author Rayzel Shulman, MD, PhD, an endocrinologist at The Hospital for Sick Children in Toronto and associate professor of pediatrics at the University of Toronto, said in an interview.

The study was published in JAMA Network Open.
 

Increased incidence

The investigators reviewed 42 studies, including 17 that examined rates of type 1 diabetes incidence, 10 on type 2 diabetes, and 15 on DKA. The included studies all had a minimum observation period of 12 months during the pandemic and at least 12 months before it. Relative to the prepandemic period, the meta-analysis found higher rates of type 1 diabetes and DKA during the pandemic.

The review was conducted in response to questions about the methodology of study results suggesting an association between the COVID-19 pandemic and the incidence of diabetes, according to Dr. Shulman.

Although this is not the first review of studies on the connection between diabetes and COVID-19, it adds to the literature by extending the study period to 2 years of the pandemic. The longer time frame helps address potential seasonal differences in incidence and increases confidence in the results.

The investigators also sought to look at the incidence of type 2 diabetes in children but found few studies that met the study criteria. Although some studies reported rates of type 2 diabetes, most lacked information about the population, specifically, the “denominator” needed for findings regarding any association with the COVID-19 pandemic.

With greater confidence in the increased incidence of type 1 diabetes, Dr. Shulman emphasized a need to ensure sufficient resources to care for newly diagnosed patients, including education and support for families.

The study’s secondary outcome was the change in incidence rate of DKA among children with newly diagnosed diabetes. Data reported in 15 studies showed a 26% increase in DKA incidence during the first year of the pandemic.

“DKA is a serious and life-threatening condition that is preventable,” said Dr. Shulman. Symptoms of type 1 diabetes include increased thirst and urination, weight loss, and fatigue. If parents or caregivers notice these signs, Dr. Shulman advises them to seek care immediately to reduce the risk of DKA.
 

Possible mechanisms

In a comment, Elizabeth Sellers, MD, an endocrinologist at the Children’s Hospital Research Institute of Manitoba and associate professor of pediatrics at the University of Manitoba, both in Winnipeg, said the study’s findings on DKA are an important reminder to be attentive to symptoms of diabetes. Dr. Sellers did not participate in the meta-analysis.

One possible explanation for the increase is a hesitancy to seek care among parents and caregivers during the pandemic. “I think we use that information and turn it into a positive,” said Dr. Sellers, by increasing recognition of the symptoms. Dr. Sellers, whose research is included in the review, is part of an initiative by the Canadian Pediatric Endocrine Group to increase diabetes awareness.

The study provides important findings, particularly the second-year results, but is not designed to answer why there has been an increase in diabetes incidence, said Dr. Sellers. “You have to identify the problem first and then you can go back and look at mechanisms.”

The meta-analysis did not seek to draw conclusions about the underlying mechanisms that would explain changes in diabetes incidence but rather indicates a need for further studies to seek a better understanding of the connection. Several theories may be considered, wrote Clemens Kamrath, MD, of the Centre of Child and Adolescent Medicine at Justus Liebig University in Giessen, Germany, and colleagues in an accompanying editorial.

Studies have suggested a direct effect of infections such as COVID-19, whereby the virus damages insulin-producing beta cells. However, the commentary notes these studies do not account for asymptomatic infections among children.

Dr. Kamrath and colleagues also considered the indirect effects of the COVID-19 pandemic, which they indicate may be more likely than direct effects. These indirect effects include autoimmunity and environmental changes that occurred during the pandemic.

Researchers will need to continue monitoring the data to see if the trend persists and continue working to determine the mechanisms, said Dr. Schulman. “I don’t think this is the end of the story.”

The study was supported in part by grant funding from the department of pediatrics at The Hospital for Sick Children. Dr. Shulman, Dr. Sellers, and Dr. Kamrath reported no relevant financial relationships.

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

The incidence of type 1 diabetes has risen during the COVID-19 pandemic, according to a recent meta-analysis.

The review compared 2 years of data from during the pandemic to data from a prepandemic period, and showed a higher incidence of type 1 diabetes in the first year (incidence rate ratio, 1.14) and second year (IRR, 1.27) of the pandemic. The investigators also found an increase in the incidence of diabetic ketoacidosis (DKA) (IRR, 1.26).

The meta-analysis included 17 studies of 38,149 children and adolescents with newly diagnosed type 1 diabetes. “Putting them all together really gave us more confidence to say this is something that we think is real,” study author Rayzel Shulman, MD, PhD, an endocrinologist at The Hospital for Sick Children in Toronto and associate professor of pediatrics at the University of Toronto, said in an interview.

The study was published in JAMA Network Open.
 

Increased incidence

The investigators reviewed 42 studies, including 17 that examined rates of type 1 diabetes incidence, 10 on type 2 diabetes, and 15 on DKA. The included studies all had a minimum observation period of 12 months during the pandemic and at least 12 months before it. Relative to the prepandemic period, the meta-analysis found higher rates of type 1 diabetes and DKA during the pandemic.

The review was conducted in response to questions about the methodology of study results suggesting an association between the COVID-19 pandemic and the incidence of diabetes, according to Dr. Shulman.

Although this is not the first review of studies on the connection between diabetes and COVID-19, it adds to the literature by extending the study period to 2 years of the pandemic. The longer time frame helps address potential seasonal differences in incidence and increases confidence in the results.

The investigators also sought to look at the incidence of type 2 diabetes in children but found few studies that met the study criteria. Although some studies reported rates of type 2 diabetes, most lacked information about the population, specifically, the “denominator” needed for findings regarding any association with the COVID-19 pandemic.

With greater confidence in the increased incidence of type 1 diabetes, Dr. Shulman emphasized a need to ensure sufficient resources to care for newly diagnosed patients, including education and support for families.

The study’s secondary outcome was the change in incidence rate of DKA among children with newly diagnosed diabetes. Data reported in 15 studies showed a 26% increase in DKA incidence during the first year of the pandemic.

“DKA is a serious and life-threatening condition that is preventable,” said Dr. Shulman. Symptoms of type 1 diabetes include increased thirst and urination, weight loss, and fatigue. If parents or caregivers notice these signs, Dr. Shulman advises them to seek care immediately to reduce the risk of DKA.
 

Possible mechanisms

In a comment, Elizabeth Sellers, MD, an endocrinologist at the Children’s Hospital Research Institute of Manitoba and associate professor of pediatrics at the University of Manitoba, both in Winnipeg, said the study’s findings on DKA are an important reminder to be attentive to symptoms of diabetes. Dr. Sellers did not participate in the meta-analysis.

One possible explanation for the increase is a hesitancy to seek care among parents and caregivers during the pandemic. “I think we use that information and turn it into a positive,” said Dr. Sellers, by increasing recognition of the symptoms. Dr. Sellers, whose research is included in the review, is part of an initiative by the Canadian Pediatric Endocrine Group to increase diabetes awareness.

The study provides important findings, particularly the second-year results, but is not designed to answer why there has been an increase in diabetes incidence, said Dr. Sellers. “You have to identify the problem first and then you can go back and look at mechanisms.”

The meta-analysis did not seek to draw conclusions about the underlying mechanisms that would explain changes in diabetes incidence but rather indicates a need for further studies to seek a better understanding of the connection. Several theories may be considered, wrote Clemens Kamrath, MD, of the Centre of Child and Adolescent Medicine at Justus Liebig University in Giessen, Germany, and colleagues in an accompanying editorial.

Studies have suggested a direct effect of infections such as COVID-19, whereby the virus damages insulin-producing beta cells. However, the commentary notes these studies do not account for asymptomatic infections among children.

Dr. Kamrath and colleagues also considered the indirect effects of the COVID-19 pandemic, which they indicate may be more likely than direct effects. These indirect effects include autoimmunity and environmental changes that occurred during the pandemic.

Researchers will need to continue monitoring the data to see if the trend persists and continue working to determine the mechanisms, said Dr. Schulman. “I don’t think this is the end of the story.”

The study was supported in part by grant funding from the department of pediatrics at The Hospital for Sick Children. Dr. Shulman, Dr. Sellers, and Dr. Kamrath reported no relevant financial relationships.

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

The incidence of type 1 diabetes has risen during the COVID-19 pandemic, according to a recent meta-analysis.

The review compared 2 years of data from during the pandemic to data from a prepandemic period, and showed a higher incidence of type 1 diabetes in the first year (incidence rate ratio, 1.14) and second year (IRR, 1.27) of the pandemic. The investigators also found an increase in the incidence of diabetic ketoacidosis (DKA) (IRR, 1.26).

The meta-analysis included 17 studies of 38,149 children and adolescents with newly diagnosed type 1 diabetes. “Putting them all together really gave us more confidence to say this is something that we think is real,” study author Rayzel Shulman, MD, PhD, an endocrinologist at The Hospital for Sick Children in Toronto and associate professor of pediatrics at the University of Toronto, said in an interview.

The study was published in JAMA Network Open.
 

Increased incidence

The investigators reviewed 42 studies, including 17 that examined rates of type 1 diabetes incidence, 10 on type 2 diabetes, and 15 on DKA. The included studies all had a minimum observation period of 12 months during the pandemic and at least 12 months before it. Relative to the prepandemic period, the meta-analysis found higher rates of type 1 diabetes and DKA during the pandemic.

The review was conducted in response to questions about the methodology of study results suggesting an association between the COVID-19 pandemic and the incidence of diabetes, according to Dr. Shulman.

Although this is not the first review of studies on the connection between diabetes and COVID-19, it adds to the literature by extending the study period to 2 years of the pandemic. The longer time frame helps address potential seasonal differences in incidence and increases confidence in the results.

The investigators also sought to look at the incidence of type 2 diabetes in children but found few studies that met the study criteria. Although some studies reported rates of type 2 diabetes, most lacked information about the population, specifically, the “denominator” needed for findings regarding any association with the COVID-19 pandemic.

With greater confidence in the increased incidence of type 1 diabetes, Dr. Shulman emphasized a need to ensure sufficient resources to care for newly diagnosed patients, including education and support for families.

The study’s secondary outcome was the change in incidence rate of DKA among children with newly diagnosed diabetes. Data reported in 15 studies showed a 26% increase in DKA incidence during the first year of the pandemic.

“DKA is a serious and life-threatening condition that is preventable,” said Dr. Shulman. Symptoms of type 1 diabetes include increased thirst and urination, weight loss, and fatigue. If parents or caregivers notice these signs, Dr. Shulman advises them to seek care immediately to reduce the risk of DKA.
 

Possible mechanisms

In a comment, Elizabeth Sellers, MD, an endocrinologist at the Children’s Hospital Research Institute of Manitoba and associate professor of pediatrics at the University of Manitoba, both in Winnipeg, said the study’s findings on DKA are an important reminder to be attentive to symptoms of diabetes. Dr. Sellers did not participate in the meta-analysis.

One possible explanation for the increase is a hesitancy to seek care among parents and caregivers during the pandemic. “I think we use that information and turn it into a positive,” said Dr. Sellers, by increasing recognition of the symptoms. Dr. Sellers, whose research is included in the review, is part of an initiative by the Canadian Pediatric Endocrine Group to increase diabetes awareness.

The study provides important findings, particularly the second-year results, but is not designed to answer why there has been an increase in diabetes incidence, said Dr. Sellers. “You have to identify the problem first and then you can go back and look at mechanisms.”

The meta-analysis did not seek to draw conclusions about the underlying mechanisms that would explain changes in diabetes incidence but rather indicates a need for further studies to seek a better understanding of the connection. Several theories may be considered, wrote Clemens Kamrath, MD, of the Centre of Child and Adolescent Medicine at Justus Liebig University in Giessen, Germany, and colleagues in an accompanying editorial.

Studies have suggested a direct effect of infections such as COVID-19, whereby the virus damages insulin-producing beta cells. However, the commentary notes these studies do not account for asymptomatic infections among children.

Dr. Kamrath and colleagues also considered the indirect effects of the COVID-19 pandemic, which they indicate may be more likely than direct effects. These indirect effects include autoimmunity and environmental changes that occurred during the pandemic.

Researchers will need to continue monitoring the data to see if the trend persists and continue working to determine the mechanisms, said Dr. Schulman. “I don’t think this is the end of the story.”

The study was supported in part by grant funding from the department of pediatrics at The Hospital for Sick Children. Dr. Shulman, Dr. Sellers, and Dr. Kamrath reported no relevant financial relationships.

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

The Food and Drug Administration’s approval today of the first birth control pill for women to be available without a prescription is being hailed by many as a long-needed development, but there remain questions to be resolved, including how much the drug will cost and how it will be used.

Olivier Le Moal/Getty Images

The drug, Opill, is expected to be available early next year, and its maker has yet to reveal a retail price. It is the same birth control pill that has been available by prescription for 50 years. But for the first time, women will be able to buy the contraception at a local pharmacy, other retail locations, or online without having to see a doctor first.

Likely to drive debate

Contraception in the United States is not without controversy. The FDA’s approval spurred reactions both for and against making hormonal birth control for women available without a prescription.

“It’s an exciting time, especially right now when reproductive rights are being curtailed in a lot of states. Giving people an additional option for contraception will change people’s lives,” said Beverly Gray, MD, division director of Women’s Community and Population Health at Duke University Medical Center in Durham, N.C.

“It’s a huge win for patients who need better access to contraception,” said Dr. Gray, who is also a spokesperson for the American College of Obstetricians and Gynecologists.

Women who want hormonal birth control but live in areas without convenient access to a doctor, women who cannot easily take time off of work to see a doctor and get a prescription filled, and women without insurance are examples of people who will benefit, she said.

The Catholic Medical Association, in contrast, expressed “deep concern and disappointment” after an FDA advisory committee’s unanimous vote on May 11 recommending the drug be available over the counter. In a statement after the vote, the group cited “extensive medical studies demonstrating the risks and adverse effects of hormonal contraceptives,” adding that “the social impact of [full approval] would be dramatic.”

But doctors largely disagreed.

“It is definitely a huge win for reproductive autonomy. I’m glad that the FDA is prioritizing patient safety and well-being over politics,” said Catherine Cansino, MD, MPH, an ob.gyn. and clinical professor in the University of California Davis department of obstetrics and gynecology. She said the FDA approved the over-the-counter version because the medication is safe.

While opponents like the Catholic Medical Association cite safety concerns and believe doctors should screen all women before prescribing hormonal contraception, Dr. Gray disagreed. “There’s a lot of evidence that patients can figure out if a progestin-only pill is right for them and safe for them. Medical professionals don’t have to be the gatekeepers for contraception,” she said.

Pricing unknown

Whether insurance companies will pay for Opill now that it will be available without a prescription remains unknown. For some medications, paying a copay through insurance can be less expensive than buying at a retail price.

“Although pricing issues will be relevant, the FDA’s decision will enhance women’s access to hormonal birth control,” said Andrew M. Kaunitz, MD, a professor and associate chairman in the department of obstetrics and gynecology at the University of Florida College of Medicine in Jacksonville.

The drugmaker, Perrigo, based in Ireland, has not yet announced how much the pill will cost. The price tag could affect how widely available this form of birth control is. The drug has been shown to be as much as 93% effective for pregnancy prevention. Perrigo says it plans to make the pill available at low or no cost to some women.

Caveats to consider

There are some women for whom hormonal contraceptives have always carried greater risks. For example, women who have breast cancer or a history of breast cancer should not use hormonal contraceptives, the FDA said in a news release announcing the approval. Women with other types of cancer should check with their doctors first, the agency noted.

Women who smoke, who take some medications to lower blood pressure, or who have migraines should also take caution, Dr. Cansino said. “People with migraines may not be suitable for over-the-counter oral contraceptives. But a simple screening through a provider can identify whether you are truly eligible or not.”

Irregular bleeding, headaches, dizziness, nausea, increased appetite, belly pain, cramps, or bloating are the most common side effects of Opill, the FDA said.

The Opill is a progestin-only birth control pill. Similar pills have been available in the United Kingdiom for about 2 years, often referred to as “mini pills” because they contain a single hormone. In contrast, prescription birth control pills in the United States and elsewhere contain more than one hormone, estrogen and progestin, to prevent pregnancy.

Prescription pill packs for combination contraception often feature a week of placebo pills without an active ingredient. While skipping a placebo pill might not make a difference in pregnancy prevention, Opill is different. Every pill in the packet will contain medication, Gray said. “So it’s important to take the pill the same time every day for it to be most effective.”

Even though this may mean one less visit to your doctor, Dr. Kaunitz hopes women will stay up to date on their other medical checkups. “One of our challenges as providers of care to women will be to encourage them to continue to receive important services, including cancer screening and vaccinations, even while they can initiate and continue hormonal contraception without contact with a provider.”

Just the beginning?

The American Medical Association hopes this approval signals more to come.

“While we applaud this move, the AMA continues to urge the FDA and HHS to consider a variety of oral contraceptive options for over-the-counter use,” the association, which has more than 250,000 doctor members, said in a statement. “It is important patients have options when choosing which type of birth control works best for them,”

The American College of Obstetricians and Gynecologists said the FDA’s decision will help many women. “We are glad that more patients will now be empowered to choose when and where they obtain a safe method of contraception without having to wait for a medical appointment or for a prescription to be filled,” Verda J. Hicks, MD, the group’s president, and Christopher M. Zahn, MD, interim chief executive officer, said in a statement.

“Allowing individuals to access birth control at their local pharmacy or drug store will eliminate some barriers,” they said.

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

This article was updated 7/13/23.

The Food and Drug Administration’s approval today of the first birth control pill for women to be available without a prescription is being hailed by many as a long-needed development, but there remain questions to be resolved, including how much the drug will cost and how it will be used.

Olivier Le Moal/Getty Images

The drug, Opill, is expected to be available early next year, and its maker has yet to reveal a retail price. It is the same birth control pill that has been available by prescription for 50 years. But for the first time, women will be able to buy the contraception at a local pharmacy, other retail locations, or online without having to see a doctor first.

Likely to drive debate

Contraception in the United States is not without controversy. The FDA’s approval spurred reactions both for and against making hormonal birth control for women available without a prescription.

“It’s an exciting time, especially right now when reproductive rights are being curtailed in a lot of states. Giving people an additional option for contraception will change people’s lives,” said Beverly Gray, MD, division director of Women’s Community and Population Health at Duke University Medical Center in Durham, N.C.

“It’s a huge win for patients who need better access to contraception,” said Dr. Gray, who is also a spokesperson for the American College of Obstetricians and Gynecologists.

Women who want hormonal birth control but live in areas without convenient access to a doctor, women who cannot easily take time off of work to see a doctor and get a prescription filled, and women without insurance are examples of people who will benefit, she said.

The Catholic Medical Association, in contrast, expressed “deep concern and disappointment” after an FDA advisory committee’s unanimous vote on May 11 recommending the drug be available over the counter. In a statement after the vote, the group cited “extensive medical studies demonstrating the risks and adverse effects of hormonal contraceptives,” adding that “the social impact of [full approval] would be dramatic.”

But doctors largely disagreed.

“It is definitely a huge win for reproductive autonomy. I’m glad that the FDA is prioritizing patient safety and well-being over politics,” said Catherine Cansino, MD, MPH, an ob.gyn. and clinical professor in the University of California Davis department of obstetrics and gynecology. She said the FDA approved the over-the-counter version because the medication is safe.

While opponents like the Catholic Medical Association cite safety concerns and believe doctors should screen all women before prescribing hormonal contraception, Dr. Gray disagreed. “There’s a lot of evidence that patients can figure out if a progestin-only pill is right for them and safe for them. Medical professionals don’t have to be the gatekeepers for contraception,” she said.

Pricing unknown

Whether insurance companies will pay for Opill now that it will be available without a prescription remains unknown. For some medications, paying a copay through insurance can be less expensive than buying at a retail price.

“Although pricing issues will be relevant, the FDA’s decision will enhance women’s access to hormonal birth control,” said Andrew M. Kaunitz, MD, a professor and associate chairman in the department of obstetrics and gynecology at the University of Florida College of Medicine in Jacksonville.

The drugmaker, Perrigo, based in Ireland, has not yet announced how much the pill will cost. The price tag could affect how widely available this form of birth control is. The drug has been shown to be as much as 93% effective for pregnancy prevention. Perrigo says it plans to make the pill available at low or no cost to some women.

Caveats to consider

There are some women for whom hormonal contraceptives have always carried greater risks. For example, women who have breast cancer or a history of breast cancer should not use hormonal contraceptives, the FDA said in a news release announcing the approval. Women with other types of cancer should check with their doctors first, the agency noted.

Women who smoke, who take some medications to lower blood pressure, or who have migraines should also take caution, Dr. Cansino said. “People with migraines may not be suitable for over-the-counter oral contraceptives. But a simple screening through a provider can identify whether you are truly eligible or not.”

Irregular bleeding, headaches, dizziness, nausea, increased appetite, belly pain, cramps, or bloating are the most common side effects of Opill, the FDA said.

The Opill is a progestin-only birth control pill. Similar pills have been available in the United Kingdiom for about 2 years, often referred to as “mini pills” because they contain a single hormone. In contrast, prescription birth control pills in the United States and elsewhere contain more than one hormone, estrogen and progestin, to prevent pregnancy.

Prescription pill packs for combination contraception often feature a week of placebo pills without an active ingredient. While skipping a placebo pill might not make a difference in pregnancy prevention, Opill is different. Every pill in the packet will contain medication, Gray said. “So it’s important to take the pill the same time every day for it to be most effective.”

Even though this may mean one less visit to your doctor, Dr. Kaunitz hopes women will stay up to date on their other medical checkups. “One of our challenges as providers of care to women will be to encourage them to continue to receive important services, including cancer screening and vaccinations, even while they can initiate and continue hormonal contraception without contact with a provider.”

Just the beginning?

The American Medical Association hopes this approval signals more to come.

“While we applaud this move, the AMA continues to urge the FDA and HHS to consider a variety of oral contraceptive options for over-the-counter use,” the association, which has more than 250,000 doctor members, said in a statement. “It is important patients have options when choosing which type of birth control works best for them,”

The American College of Obstetricians and Gynecologists said the FDA’s decision will help many women. “We are glad that more patients will now be empowered to choose when and where they obtain a safe method of contraception without having to wait for a medical appointment or for a prescription to be filled,” Verda J. Hicks, MD, the group’s president, and Christopher M. Zahn, MD, interim chief executive officer, said in a statement.

“Allowing individuals to access birth control at their local pharmacy or drug store will eliminate some barriers,” they said.

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

This article was updated 7/13/23.

The Food and Drug Administration’s approval today of the first birth control pill for women to be available without a prescription is being hailed by many as a long-needed development, but there remain questions to be resolved, including how much the drug will cost and how it will be used.

Olivier Le Moal/Getty Images

The drug, Opill, is expected to be available early next year, and its maker has yet to reveal a retail price. It is the same birth control pill that has been available by prescription for 50 years. But for the first time, women will be able to buy the contraception at a local pharmacy, other retail locations, or online without having to see a doctor first.

Likely to drive debate

Contraception in the United States is not without controversy. The FDA’s approval spurred reactions both for and against making hormonal birth control for women available without a prescription.

“It’s an exciting time, especially right now when reproductive rights are being curtailed in a lot of states. Giving people an additional option for contraception will change people’s lives,” said Beverly Gray, MD, division director of Women’s Community and Population Health at Duke University Medical Center in Durham, N.C.

“It’s a huge win for patients who need better access to contraception,” said Dr. Gray, who is also a spokesperson for the American College of Obstetricians and Gynecologists.

Women who want hormonal birth control but live in areas without convenient access to a doctor, women who cannot easily take time off of work to see a doctor and get a prescription filled, and women without insurance are examples of people who will benefit, she said.

The Catholic Medical Association, in contrast, expressed “deep concern and disappointment” after an FDA advisory committee’s unanimous vote on May 11 recommending the drug be available over the counter. In a statement after the vote, the group cited “extensive medical studies demonstrating the risks and adverse effects of hormonal contraceptives,” adding that “the social impact of [full approval] would be dramatic.”

But doctors largely disagreed.

“It is definitely a huge win for reproductive autonomy. I’m glad that the FDA is prioritizing patient safety and well-being over politics,” said Catherine Cansino, MD, MPH, an ob.gyn. and clinical professor in the University of California Davis department of obstetrics and gynecology. She said the FDA approved the over-the-counter version because the medication is safe.

While opponents like the Catholic Medical Association cite safety concerns and believe doctors should screen all women before prescribing hormonal contraception, Dr. Gray disagreed. “There’s a lot of evidence that patients can figure out if a progestin-only pill is right for them and safe for them. Medical professionals don’t have to be the gatekeepers for contraception,” she said.

Pricing unknown

Whether insurance companies will pay for Opill now that it will be available without a prescription remains unknown. For some medications, paying a copay through insurance can be less expensive than buying at a retail price.

“Although pricing issues will be relevant, the FDA’s decision will enhance women’s access to hormonal birth control,” said Andrew M. Kaunitz, MD, a professor and associate chairman in the department of obstetrics and gynecology at the University of Florida College of Medicine in Jacksonville.

The drugmaker, Perrigo, based in Ireland, has not yet announced how much the pill will cost. The price tag could affect how widely available this form of birth control is. The drug has been shown to be as much as 93% effective for pregnancy prevention. Perrigo says it plans to make the pill available at low or no cost to some women.

Caveats to consider

There are some women for whom hormonal contraceptives have always carried greater risks. For example, women who have breast cancer or a history of breast cancer should not use hormonal contraceptives, the FDA said in a news release announcing the approval. Women with other types of cancer should check with their doctors first, the agency noted.

Women who smoke, who take some medications to lower blood pressure, or who have migraines should also take caution, Dr. Cansino said. “People with migraines may not be suitable for over-the-counter oral contraceptives. But a simple screening through a provider can identify whether you are truly eligible or not.”

Irregular bleeding, headaches, dizziness, nausea, increased appetite, belly pain, cramps, or bloating are the most common side effects of Opill, the FDA said.

The Opill is a progestin-only birth control pill. Similar pills have been available in the United Kingdiom for about 2 years, often referred to as “mini pills” because they contain a single hormone. In contrast, prescription birth control pills in the United States and elsewhere contain more than one hormone, estrogen and progestin, to prevent pregnancy.

Prescription pill packs for combination contraception often feature a week of placebo pills without an active ingredient. While skipping a placebo pill might not make a difference in pregnancy prevention, Opill is different. Every pill in the packet will contain medication, Gray said. “So it’s important to take the pill the same time every day for it to be most effective.”

Even though this may mean one less visit to your doctor, Dr. Kaunitz hopes women will stay up to date on their other medical checkups. “One of our challenges as providers of care to women will be to encourage them to continue to receive important services, including cancer screening and vaccinations, even while they can initiate and continue hormonal contraception without contact with a provider.”

Just the beginning?

The American Medical Association hopes this approval signals more to come.

“While we applaud this move, the AMA continues to urge the FDA and HHS to consider a variety of oral contraceptive options for over-the-counter use,” the association, which has more than 250,000 doctor members, said in a statement. “It is important patients have options when choosing which type of birth control works best for them,”

The American College of Obstetricians and Gynecologists said the FDA’s decision will help many women. “We are glad that more patients will now be empowered to choose when and where they obtain a safe method of contraception without having to wait for a medical appointment or for a prescription to be filled,” Verda J. Hicks, MD, the group’s president, and Christopher M. Zahn, MD, interim chief executive officer, said in a statement.

“Allowing individuals to access birth control at their local pharmacy or drug store will eliminate some barriers,” they said.

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

This article was updated 7/13/23.