In my last column, I discussed blogging as a great way to capture the attention of anyone interested in your practice, especially prospective patients. If you are already blogging – or would like to consider a less crowded and competitive activity – podcasting might be the answer. At this writing (November 2022), more than 600 million blogs are online, compared with about 2 million podcasts, and relatively few of them are run by physicians. With podcasts, you have a better chance of standing out in a crowded online world.

Starting a podcast is not difficult, but there are several steps you need to go through before launching one.

As with blogging, start by outlining a long-range plan. Your general topic will probably be your specialty, but you will need to narrow your focus to a few specific subjects, such as the problems you see most often, or a subspecialty that you concentrate on. You can always expand your topic later, as you get more popular. Choose a name for your podcast, and purchase a domain name that accurately describes it.

You will also need to choose a hosting service. Numerous inexpensive hosting platforms are available, and a simple Google search will find them for you. Many of them provide free learning materials, helpful creative tools, and customer support to get you through the confusing technical aspects. They can also help you choose a music introduction (to add a bit of polish), and help you piece together your audio segments. Buzzsprout, RSS.com, and Podbean get good reviews on many sites. (As always, I have no financial interest in any company or service mentioned herein.)

Hosting services can assist you in creating a template – a framework that you can reuse each time you record an episode – containing your intro and exit music, tracks for your conversations, etc. This will make your podcasts instantly recognizable each time your listeners tune in.

Many podcasting experts recommend recruiting a co-host. This can be an associate within your practice, a friend who practices elsewhere, or perhaps a resident in an academic setting. You will be able to spread the workload of creating, editing, and promoting. Plus, it is much easier to generate interesting content when two people are having a conversation, rather than one person lecturing from a prepared script. You might also consider having multiple co-hosts, either to expand episodes into group discussions, or to take turns working with you in covering different subjects.

How long you make your podcast is entirely up to you. Some consultants recommend specific time frames, such as 5 minutes (because that’s an average attention span), or 28 minutes (because that’s the average driving commute time). There are short podcasts and long ones; whatever works for you is fine, as long as you don’t drift off the topic. Furthermore, no one says they must all be the same length; when you are finished talking, you are done. And no one says you must stick with one subject throughout. Combining several short segments might hold more listeners’ interest and will make it easier to share small clips on social media.

Content guidelines are similar to those for blogs. Give people content that will be of interest or benefit to them. Talk about subjects – medical and otherwise – that are relevant to your practice or are prominent in the news.

As with blogs, try to avoid polarizing political discussions, and while it’s fine to discuss treatments and procedures that you offer, aggressive solicitation tends to make viewers look elsewhere. Keep any medical advice in general terms; don’t portray any specific patients as examples.

When your podcast is ready, your hosting platform will show you how to submit it to iTunes, and how to submit your podcast RSS feed to other podcast directories. As you upload new episodes, your host will automatically update your RSS feed, so that any directory you are listed on will receive the new episode.

Once you are uploaded, you can use your host’s social sharing tools to spread the word. As with blogs, use social media, such as your practice’s Facebook page, to push podcast updates into patients’ feeds and track relevant Twitter hashtags to find online communities that might be interested in your subject matter. You should also find your episode embed code (which your host will have) and place it in a prominent place on your website so patients can listen directly from there.

Transcriptions are another excellent promotional tool. Search engines will “read” your podcasts and list them in searches. Some podcast hosts will do transcribing for a fee, but there are independent transcription services as well.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

In my last column, I discussed blogging as a great way to capture the attention of anyone interested in your practice, especially prospective patients. If you are already blogging – or would like to consider a less crowded and competitive activity – podcasting might be the answer. At this writing (November 2022), more than 600 million blogs are online, compared with about 2 million podcasts, and relatively few of them are run by physicians. With podcasts, you have a better chance of standing out in a crowded online world.

Starting a podcast is not difficult, but there are several steps you need to go through before launching one.

As with blogging, start by outlining a long-range plan. Your general topic will probably be your specialty, but you will need to narrow your focus to a few specific subjects, such as the problems you see most often, or a subspecialty that you concentrate on. You can always expand your topic later, as you get more popular. Choose a name for your podcast, and purchase a domain name that accurately describes it.

You will also need to choose a hosting service. Numerous inexpensive hosting platforms are available, and a simple Google search will find them for you. Many of them provide free learning materials, helpful creative tools, and customer support to get you through the confusing technical aspects. They can also help you choose a music introduction (to add a bit of polish), and help you piece together your audio segments. Buzzsprout, RSS.com, and Podbean get good reviews on many sites. (As always, I have no financial interest in any company or service mentioned herein.)

Hosting services can assist you in creating a template – a framework that you can reuse each time you record an episode – containing your intro and exit music, tracks for your conversations, etc. This will make your podcasts instantly recognizable each time your listeners tune in.

Many podcasting experts recommend recruiting a co-host. This can be an associate within your practice, a friend who practices elsewhere, or perhaps a resident in an academic setting. You will be able to spread the workload of creating, editing, and promoting. Plus, it is much easier to generate interesting content when two people are having a conversation, rather than one person lecturing from a prepared script. You might also consider having multiple co-hosts, either to expand episodes into group discussions, or to take turns working with you in covering different subjects.

How long you make your podcast is entirely up to you. Some consultants recommend specific time frames, such as 5 minutes (because that’s an average attention span), or 28 minutes (because that’s the average driving commute time). There are short podcasts and long ones; whatever works for you is fine, as long as you don’t drift off the topic. Furthermore, no one says they must all be the same length; when you are finished talking, you are done. And no one says you must stick with one subject throughout. Combining several short segments might hold more listeners’ interest and will make it easier to share small clips on social media.

Content guidelines are similar to those for blogs. Give people content that will be of interest or benefit to them. Talk about subjects – medical and otherwise – that are relevant to your practice or are prominent in the news.

As with blogs, try to avoid polarizing political discussions, and while it’s fine to discuss treatments and procedures that you offer, aggressive solicitation tends to make viewers look elsewhere. Keep any medical advice in general terms; don’t portray any specific patients as examples.

When your podcast is ready, your hosting platform will show you how to submit it to iTunes, and how to submit your podcast RSS feed to other podcast directories. As you upload new episodes, your host will automatically update your RSS feed, so that any directory you are listed on will receive the new episode.

Once you are uploaded, you can use your host’s social sharing tools to spread the word. As with blogs, use social media, such as your practice’s Facebook page, to push podcast updates into patients’ feeds and track relevant Twitter hashtags to find online communities that might be interested in your subject matter. You should also find your episode embed code (which your host will have) and place it in a prominent place on your website so patients can listen directly from there.

Transcriptions are another excellent promotional tool. Search engines will “read” your podcasts and list them in searches. Some podcast hosts will do transcribing for a fee, but there are independent transcription services as well.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

In my last column, I discussed blogging as a great way to capture the attention of anyone interested in your practice, especially prospective patients. If you are already blogging – or would like to consider a less crowded and competitive activity – podcasting might be the answer. At this writing (November 2022), more than 600 million blogs are online, compared with about 2 million podcasts, and relatively few of them are run by physicians. With podcasts, you have a better chance of standing out in a crowded online world.

Starting a podcast is not difficult, but there are several steps you need to go through before launching one.

As with blogging, start by outlining a long-range plan. Your general topic will probably be your specialty, but you will need to narrow your focus to a few specific subjects, such as the problems you see most often, or a subspecialty that you concentrate on. You can always expand your topic later, as you get more popular. Choose a name for your podcast, and purchase a domain name that accurately describes it.

You will also need to choose a hosting service. Numerous inexpensive hosting platforms are available, and a simple Google search will find them for you. Many of them provide free learning materials, helpful creative tools, and customer support to get you through the confusing technical aspects. They can also help you choose a music introduction (to add a bit of polish), and help you piece together your audio segments. Buzzsprout, RSS.com, and Podbean get good reviews on many sites. (As always, I have no financial interest in any company or service mentioned herein.)

Hosting services can assist you in creating a template – a framework that you can reuse each time you record an episode – containing your intro and exit music, tracks for your conversations, etc. This will make your podcasts instantly recognizable each time your listeners tune in.

Many podcasting experts recommend recruiting a co-host. This can be an associate within your practice, a friend who practices elsewhere, or perhaps a resident in an academic setting. You will be able to spread the workload of creating, editing, and promoting. Plus, it is much easier to generate interesting content when two people are having a conversation, rather than one person lecturing from a prepared script. You might also consider having multiple co-hosts, either to expand episodes into group discussions, or to take turns working with you in covering different subjects.

How long you make your podcast is entirely up to you. Some consultants recommend specific time frames, such as 5 minutes (because that’s an average attention span), or 28 minutes (because that’s the average driving commute time). There are short podcasts and long ones; whatever works for you is fine, as long as you don’t drift off the topic. Furthermore, no one says they must all be the same length; when you are finished talking, you are done. And no one says you must stick with one subject throughout. Combining several short segments might hold more listeners’ interest and will make it easier to share small clips on social media.

Content guidelines are similar to those for blogs. Give people content that will be of interest or benefit to them. Talk about subjects – medical and otherwise – that are relevant to your practice or are prominent in the news.

As with blogs, try to avoid polarizing political discussions, and while it’s fine to discuss treatments and procedures that you offer, aggressive solicitation tends to make viewers look elsewhere. Keep any medical advice in general terms; don’t portray any specific patients as examples.

When your podcast is ready, your hosting platform will show you how to submit it to iTunes, and how to submit your podcast RSS feed to other podcast directories. As you upload new episodes, your host will automatically update your RSS feed, so that any directory you are listed on will receive the new episode.

Once you are uploaded, you can use your host’s social sharing tools to spread the word. As with blogs, use social media, such as your practice’s Facebook page, to push podcast updates into patients’ feeds and track relevant Twitter hashtags to find online communities that might be interested in your subject matter. You should also find your episode embed code (which your host will have) and place it in a prominent place on your website so patients can listen directly from there.

Transcriptions are another excellent promotional tool. Search engines will “read” your podcasts and list them in searches. Some podcast hosts will do transcribing for a fee, but there are independent transcription services as well.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

PHILADELPHIA – Aggressive therapy using conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in combination with biologic agents early, soon after a child is diagnosed with polyarticular juvenile idiopathic arthritis (pJIA), enabled more patients to achieve clinical remission and longer times in inactive disease than more conventional therapeutic approaches, 3-year results of prospective, observational study demonstrated.

The results of The Childhood Arthritis and Rheumatology Research Alliance STOP-JIA study, which Yukiko Kimura, MD, presented at the annual meeting of the American College of Rheumatology, showed early combination therapy had benefits, compared with other treatment strategies that were more evident at 3 years than at 1 year of study.

“The STOP-JIA study showed that, after 3 years, patients who started a biologic early on in combination with methotrexate spent more time in inactive disease and achieved clinical remission more often when compared to those started on traditional step-up therapy,” Dr. Kimura, chief of pediatric rheumatology at Hackensack (N.J.) Meridian Health and professor of pediatrics at the Hackensack Meridian School of Medicine, said at a press conference. “This study shows that the treatment of poly-JIA patients receive initially very early on in their disease matters even 3 years after that treatment was started.”

The study compared three CARRA consensus treatment plans (CTP) for untreated pediatric pJIA patients: step-up (SU) – starting conventional synthetic DMARD therapy and adding a biologic if needed after 3 or more months; early-combination (EC) therapy – starting synthetic and biologic DMARDs together; and biologic first (BF) therapy – starting biologic DMARD monotherapy.

Dr. Kimura explained the rationale for the study. “Since biologic treatments were introduced more than 20 years ago, the prognosis for JIA significantly improved. These very effective medicines often work wonders, quickly reducing pain and inflammation in joint disease activity,” she said in the press conference. “What is not known, however, is when is the best time to start these very effective treatments.”

The most common approach is to start with a synthetic DMARD, typically methotrexate, and wait before starting a biologic, Dr. Kimura said.

“But even though methotrexate can work very well by itself, it does not work for every patient, and we don’t know whether waiting months for it to work and then starting a biologic might potentially lessen their effectiveness,” Dr. Kimura added. “We don’t know if there’s a window of opportunity that’s lost while waiting to see whether methotrexate will work.”

The study originally enrolled 400 patients, 297 of whom completed the 3-year visit – 190 in SU, 76 in EC and 31 in BF. At 12 months, the study found no statistically significant difference in clinically inactive disease (CID) between the groups, Dr. Kimura said.

Even at the 3-year visit, the percentage of patients in CID off glucocorticoids and clinical Juvenile Arthritis Disease Activity Score based on 10 joints inactive disease (cJADAS 10 ID) did not differ among the three groups, Dr. Kimura said in presenting the results. “But,” she added, “greater proportions of early-combination CTP group were able to achieve clinical remissions and spend more time with inactive disease in both CID and cJADAS 10.”

A closer look at the outcomes showed some separation between early-combination therapy and the other two treatment plans. The incidence of clinical remission (at any time point over 36 months) was 67.1% in the EC group vs. 49.1% and 47.3%, respectively, in the BF and SU groups, Dr. Kimura said. “The difference between the early-combination and step-up groups was highly significant [P = .007],” she added.

EC also had an edge in the percentage of time patients spent in CID (over 36 months): 39.2% versus 32% and 27.4%, respectively, in the BF and SU groups (P = .006 for EV vs. SU), as well as cJADAS 10 ID (50.6% in EC group vs. 42.8% and 37.5%, respectively in the BF and SU groups; P = .005 for EC vs. SU).

Dr. Kimura said that the STOP JIA trial will continue with longer-term analysis and ongoing monitoring of study patients through the CARRA registry. “These longer-term analyses and readouts will be important because even though the results at 12 months didn’t seem as definitive, it seems the longer we go, the more impact we see of the treatments that were started early on in this disease.”

The findings from this study are “significantly important,” Nina T. Washington, MD, MPH, a pediatric rheumatologist at the University of New Mexico Hospital, Albuquerque, and the Mary Bridge Children’s Hospital in Tacoma, Wash., said in an interview. “At least for the past decade we’ve really been advocating towards earlier and aggressive therapy, and that’s what this study shows: the sooner you can treat this disease, the sooner you can attack those joints that are inflamed, the better outcome you give the patient.”

The study also confirms that pediatric rheumatologists are not overtreating patients with pJIA, she added.

“In a sense we’re actually treating and preventing and if you have a child that has arthritis, it’s okay to treat that child,” Dr. Washington said. “For me that’s the most reassuring thing: that I’m not necessarily going overboard. If I have a child with polyarticular JIA and they have multiple inflamed joints and I have the evidence as they’re sitting in front of me, and I treat them. I’m going to give them the best outcome.”

The Patient Centered Outcomes Research Institute provided study funding. Dr. Kimura is chair of the CARRA JIA disease research committee and cochair of the CARRA Registry and Research Oversight Committee. She disclosed a financial relationship with Genentech. Dr. Washington has no relevant relationships to disclose.
 

PHILADELPHIA – Aggressive therapy using conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in combination with biologic agents early, soon after a child is diagnosed with polyarticular juvenile idiopathic arthritis (pJIA), enabled more patients to achieve clinical remission and longer times in inactive disease than more conventional therapeutic approaches, 3-year results of prospective, observational study demonstrated.

The results of The Childhood Arthritis and Rheumatology Research Alliance STOP-JIA study, which Yukiko Kimura, MD, presented at the annual meeting of the American College of Rheumatology, showed early combination therapy had benefits, compared with other treatment strategies that were more evident at 3 years than at 1 year of study.

“The STOP-JIA study showed that, after 3 years, patients who started a biologic early on in combination with methotrexate spent more time in inactive disease and achieved clinical remission more often when compared to those started on traditional step-up therapy,” Dr. Kimura, chief of pediatric rheumatology at Hackensack (N.J.) Meridian Health and professor of pediatrics at the Hackensack Meridian School of Medicine, said at a press conference. “This study shows that the treatment of poly-JIA patients receive initially very early on in their disease matters even 3 years after that treatment was started.”

The study compared three CARRA consensus treatment plans (CTP) for untreated pediatric pJIA patients: step-up (SU) – starting conventional synthetic DMARD therapy and adding a biologic if needed after 3 or more months; early-combination (EC) therapy – starting synthetic and biologic DMARDs together; and biologic first (BF) therapy – starting biologic DMARD monotherapy.

Dr. Kimura explained the rationale for the study. “Since biologic treatments were introduced more than 20 years ago, the prognosis for JIA significantly improved. These very effective medicines often work wonders, quickly reducing pain and inflammation in joint disease activity,” she said in the press conference. “What is not known, however, is when is the best time to start these very effective treatments.”

The most common approach is to start with a synthetic DMARD, typically methotrexate, and wait before starting a biologic, Dr. Kimura said.

“But even though methotrexate can work very well by itself, it does not work for every patient, and we don’t know whether waiting months for it to work and then starting a biologic might potentially lessen their effectiveness,” Dr. Kimura added. “We don’t know if there’s a window of opportunity that’s lost while waiting to see whether methotrexate will work.”

The study originally enrolled 400 patients, 297 of whom completed the 3-year visit – 190 in SU, 76 in EC and 31 in BF. At 12 months, the study found no statistically significant difference in clinically inactive disease (CID) between the groups, Dr. Kimura said.

Even at the 3-year visit, the percentage of patients in CID off glucocorticoids and clinical Juvenile Arthritis Disease Activity Score based on 10 joints inactive disease (cJADAS 10 ID) did not differ among the three groups, Dr. Kimura said in presenting the results. “But,” she added, “greater proportions of early-combination CTP group were able to achieve clinical remissions and spend more time with inactive disease in both CID and cJADAS 10.”

A closer look at the outcomes showed some separation between early-combination therapy and the other two treatment plans. The incidence of clinical remission (at any time point over 36 months) was 67.1% in the EC group vs. 49.1% and 47.3%, respectively, in the BF and SU groups, Dr. Kimura said. “The difference between the early-combination and step-up groups was highly significant [P = .007],” she added.

EC also had an edge in the percentage of time patients spent in CID (over 36 months): 39.2% versus 32% and 27.4%, respectively, in the BF and SU groups (P = .006 for EV vs. SU), as well as cJADAS 10 ID (50.6% in EC group vs. 42.8% and 37.5%, respectively in the BF and SU groups; P = .005 for EC vs. SU).

Dr. Kimura said that the STOP JIA trial will continue with longer-term analysis and ongoing monitoring of study patients through the CARRA registry. “These longer-term analyses and readouts will be important because even though the results at 12 months didn’t seem as definitive, it seems the longer we go, the more impact we see of the treatments that were started early on in this disease.”

The findings from this study are “significantly important,” Nina T. Washington, MD, MPH, a pediatric rheumatologist at the University of New Mexico Hospital, Albuquerque, and the Mary Bridge Children’s Hospital in Tacoma, Wash., said in an interview. “At least for the past decade we’ve really been advocating towards earlier and aggressive therapy, and that’s what this study shows: the sooner you can treat this disease, the sooner you can attack those joints that are inflamed, the better outcome you give the patient.”

The study also confirms that pediatric rheumatologists are not overtreating patients with pJIA, she added.

“In a sense we’re actually treating and preventing and if you have a child that has arthritis, it’s okay to treat that child,” Dr. Washington said. “For me that’s the most reassuring thing: that I’m not necessarily going overboard. If I have a child with polyarticular JIA and they have multiple inflamed joints and I have the evidence as they’re sitting in front of me, and I treat them. I’m going to give them the best outcome.”

The Patient Centered Outcomes Research Institute provided study funding. Dr. Kimura is chair of the CARRA JIA disease research committee and cochair of the CARRA Registry and Research Oversight Committee. She disclosed a financial relationship with Genentech. Dr. Washington has no relevant relationships to disclose.
 

PHILADELPHIA – Aggressive therapy using conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in combination with biologic agents early, soon after a child is diagnosed with polyarticular juvenile idiopathic arthritis (pJIA), enabled more patients to achieve clinical remission and longer times in inactive disease than more conventional therapeutic approaches, 3-year results of prospective, observational study demonstrated.

The results of The Childhood Arthritis and Rheumatology Research Alliance STOP-JIA study, which Yukiko Kimura, MD, presented at the annual meeting of the American College of Rheumatology, showed early combination therapy had benefits, compared with other treatment strategies that were more evident at 3 years than at 1 year of study.

“The STOP-JIA study showed that, after 3 years, patients who started a biologic early on in combination with methotrexate spent more time in inactive disease and achieved clinical remission more often when compared to those started on traditional step-up therapy,” Dr. Kimura, chief of pediatric rheumatology at Hackensack (N.J.) Meridian Health and professor of pediatrics at the Hackensack Meridian School of Medicine, said at a press conference. “This study shows that the treatment of poly-JIA patients receive initially very early on in their disease matters even 3 years after that treatment was started.”

The study compared three CARRA consensus treatment plans (CTP) for untreated pediatric pJIA patients: step-up (SU) – starting conventional synthetic DMARD therapy and adding a biologic if needed after 3 or more months; early-combination (EC) therapy – starting synthetic and biologic DMARDs together; and biologic first (BF) therapy – starting biologic DMARD monotherapy.

Dr. Kimura explained the rationale for the study. “Since biologic treatments were introduced more than 20 years ago, the prognosis for JIA significantly improved. These very effective medicines often work wonders, quickly reducing pain and inflammation in joint disease activity,” she said in the press conference. “What is not known, however, is when is the best time to start these very effective treatments.”

The most common approach is to start with a synthetic DMARD, typically methotrexate, and wait before starting a biologic, Dr. Kimura said.

“But even though methotrexate can work very well by itself, it does not work for every patient, and we don’t know whether waiting months for it to work and then starting a biologic might potentially lessen their effectiveness,” Dr. Kimura added. “We don’t know if there’s a window of opportunity that’s lost while waiting to see whether methotrexate will work.”

The study originally enrolled 400 patients, 297 of whom completed the 3-year visit – 190 in SU, 76 in EC and 31 in BF. At 12 months, the study found no statistically significant difference in clinically inactive disease (CID) between the groups, Dr. Kimura said.

Even at the 3-year visit, the percentage of patients in CID off glucocorticoids and clinical Juvenile Arthritis Disease Activity Score based on 10 joints inactive disease (cJADAS 10 ID) did not differ among the three groups, Dr. Kimura said in presenting the results. “But,” she added, “greater proportions of early-combination CTP group were able to achieve clinical remissions and spend more time with inactive disease in both CID and cJADAS 10.”

A closer look at the outcomes showed some separation between early-combination therapy and the other two treatment plans. The incidence of clinical remission (at any time point over 36 months) was 67.1% in the EC group vs. 49.1% and 47.3%, respectively, in the BF and SU groups, Dr. Kimura said. “The difference between the early-combination and step-up groups was highly significant [P = .007],” she added.

EC also had an edge in the percentage of time patients spent in CID (over 36 months): 39.2% versus 32% and 27.4%, respectively, in the BF and SU groups (P = .006 for EV vs. SU), as well as cJADAS 10 ID (50.6% in EC group vs. 42.8% and 37.5%, respectively in the BF and SU groups; P = .005 for EC vs. SU).

Dr. Kimura said that the STOP JIA trial will continue with longer-term analysis and ongoing monitoring of study patients through the CARRA registry. “These longer-term analyses and readouts will be important because even though the results at 12 months didn’t seem as definitive, it seems the longer we go, the more impact we see of the treatments that were started early on in this disease.”

The findings from this study are “significantly important,” Nina T. Washington, MD, MPH, a pediatric rheumatologist at the University of New Mexico Hospital, Albuquerque, and the Mary Bridge Children’s Hospital in Tacoma, Wash., said in an interview. “At least for the past decade we’ve really been advocating towards earlier and aggressive therapy, and that’s what this study shows: the sooner you can treat this disease, the sooner you can attack those joints that are inflamed, the better outcome you give the patient.”

The study also confirms that pediatric rheumatologists are not overtreating patients with pJIA, she added.

“In a sense we’re actually treating and preventing and if you have a child that has arthritis, it’s okay to treat that child,” Dr. Washington said. “For me that’s the most reassuring thing: that I’m not necessarily going overboard. If I have a child with polyarticular JIA and they have multiple inflamed joints and I have the evidence as they’re sitting in front of me, and I treat them. I’m going to give them the best outcome.”

The Patient Centered Outcomes Research Institute provided study funding. Dr. Kimura is chair of the CARRA JIA disease research committee and cochair of the CARRA Registry and Research Oversight Committee. She disclosed a financial relationship with Genentech. Dr. Washington has no relevant relationships to disclose.
 

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

On March 26, 2022, Hawaii became the last state in the United States to lift its indoor mask mandate. By the time the current school year started, there were essentially no public school mask mandates either.

Whether you viewed the mask as an emblem of stalwart defiance against a rampaging virus, or a scarlet letter emblematic of the overreaches of public policy, you probably aren’t seeing them much anymore.

And yet, the debate about masks still rages. Who was right, who was wrong? Who trusted science, and what does the science even say? If we brought our country into marriage counseling, would we be told it is time to move on?  To look forward, not backward? To plan for our bright future together?

Perhaps. But this question isn’t really moot just because masks have largely disappeared in the United States. Variants may emerge that lead to more infection waves – and other pandemics may occur in the future. And so I think it is important to discuss a study that, with quite rigorous analysis, attempts to answer the following question: Did masking in schools lower students’ and teachers’ risk of COVID?

We are talking about this study, appearing in the New England Journal of Medicine. The short version goes like this.

Researchers had access to two important sources of data. One – an accounting of all the teachers and students (more than 300,000 of them) in 79 public, noncharter school districts in Eastern Massachusetts who tested positive for COVID every week. Two – the date that each of those school districts lifted their mask mandates or (in the case of two districts) didn’t.

Right away, I’m sure you’re thinking of potential issues. Districts that kept masks even when the statewide ban was lifted are likely quite a bit different from districts that dropped masks right away. You’re right, of course – hold on to that thought; we’ll get there.

But first – the big question – would districts that kept their masks on longer do better when it comes to the rate of COVID infection?

When everyone was masking, COVID case rates were pretty similar. Statewide mandates are lifted in late February – and most school districts remove their mandates within a few weeks – the black line are the two districts (Boston and Chelsea) where mask mandates remained in place.

As time marched on, the case rates in the various districts spread out – with districts that kept masks on longer doing better than those that took them off, and districts that kept masks on the whole time doing best of all.

Prior to the mask mandate lifting, you see very similar COVID rates in districts that would eventually remove the mandate and those that would not, with a bit of noise around the initial Omicron wave which saw just a huge amount of people get infected.

And then, after the mandate was lifted, separation. Districts that held on to masks longer had lower rates of COVID infection.

In all, over the 15-weeks of the study, there were roughly 12,000 extra cases of COVID in the mask-free school districts, which corresponds to about 35% of the total COVID burden during that time. And, yes, kids do well with COVID – on average. But 12,000 extra cases is enough to translate into a significant number of important clinical outcomes – think hospitalizations and post-COVID syndromes. And of course, maybe most importantly, missed school days. Positive kids were not allowed in class no matter what district they were in.

Okay – I promised we’d address confounders. This was not a cluster-randomized trial, where some school districts had their mandates removed based on the vicissitudes of a virtual coin flip, as much as many of us would have been interested to see that. The decision to remove masks was up to the various school boards – and they had a lot of pressure on them from many different directions. But all we need to worry about is whether any of those things that pressure a school board to keep masks on would ALSO lead to fewer COVID cases. That’s how confounders work, and how you can get false results in a study like this.

And yes – districts that kept the masks on longer were different than those who took them right off. But check out how they were different.

The districts that kept masks on longer had more low-income students. More Black and Latino students. More students per classroom. These are all risk factors that increase the risk of COVID infection. In other words, the confounding here goes in the opposite direction of the results. If anything, these factors should make you more certain that masking works.

The authors also adjusted for other factors – the community transmission of COVID-19, vaccination rates, school district sizes, and so on. No major change in the results.

One concern I addressed to Dr. Ellie Murray, the biostatistician on the study – could districts that removed masks simply have been testing more to compensate, leading to increased capturing of cases?

If anything, the schools that kept masks on were testing more than the schools that took them off – again that would tend to imply that the results are even stronger than what was reported.

Is this a perfect study? Of course not – it’s one study, it’s from one state. And the relatively large effects from keeping masks on for one or 2 weeks require us to really embrace the concept of exponential growth of infections, but, if COVID has taught us anything, it is that small changes in initial conditions can have pretty big effects.

My daughter, who goes to a public school here in Connecticut, unmasked, was home with COVID this past week. She’s fine. But you know what? She missed a week of school. I worked from home to be with her – though I didn’t test positive. And that is a real cost to both of us that I think we need to consider when we consider the value of masks. Yes, they’re annoying – but if they keep kids in school, might they be worth it? Perhaps not for now, as cases aren’t surging. But in the future, be it a particularly concerning variant, or a whole new pandemic, we should not discount the simple, cheap, and apparently beneficial act of wearing masks to decrease transmission.

Dr. Perry Wilson is an associate professor of medicine and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He disclosed no relevant conflicts of interest.

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

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

On March 26, 2022, Hawaii became the last state in the United States to lift its indoor mask mandate. By the time the current school year started, there were essentially no public school mask mandates either.

Whether you viewed the mask as an emblem of stalwart defiance against a rampaging virus, or a scarlet letter emblematic of the overreaches of public policy, you probably aren’t seeing them much anymore.

And yet, the debate about masks still rages. Who was right, who was wrong? Who trusted science, and what does the science even say? If we brought our country into marriage counseling, would we be told it is time to move on?  To look forward, not backward? To plan for our bright future together?

Perhaps. But this question isn’t really moot just because masks have largely disappeared in the United States. Variants may emerge that lead to more infection waves – and other pandemics may occur in the future. And so I think it is important to discuss a study that, with quite rigorous analysis, attempts to answer the following question: Did masking in schools lower students’ and teachers’ risk of COVID?

We are talking about this study, appearing in the New England Journal of Medicine. The short version goes like this.

Researchers had access to two important sources of data. One – an accounting of all the teachers and students (more than 300,000 of them) in 79 public, noncharter school districts in Eastern Massachusetts who tested positive for COVID every week. Two – the date that each of those school districts lifted their mask mandates or (in the case of two districts) didn’t.

Right away, I’m sure you’re thinking of potential issues. Districts that kept masks even when the statewide ban was lifted are likely quite a bit different from districts that dropped masks right away. You’re right, of course – hold on to that thought; we’ll get there.

But first – the big question – would districts that kept their masks on longer do better when it comes to the rate of COVID infection?

When everyone was masking, COVID case rates were pretty similar. Statewide mandates are lifted in late February – and most school districts remove their mandates within a few weeks – the black line are the two districts (Boston and Chelsea) where mask mandates remained in place.

As time marched on, the case rates in the various districts spread out – with districts that kept masks on longer doing better than those that took them off, and districts that kept masks on the whole time doing best of all.

Prior to the mask mandate lifting, you see very similar COVID rates in districts that would eventually remove the mandate and those that would not, with a bit of noise around the initial Omicron wave which saw just a huge amount of people get infected.

And then, after the mandate was lifted, separation. Districts that held on to masks longer had lower rates of COVID infection.

In all, over the 15-weeks of the study, there were roughly 12,000 extra cases of COVID in the mask-free school districts, which corresponds to about 35% of the total COVID burden during that time. And, yes, kids do well with COVID – on average. But 12,000 extra cases is enough to translate into a significant number of important clinical outcomes – think hospitalizations and post-COVID syndromes. And of course, maybe most importantly, missed school days. Positive kids were not allowed in class no matter what district they were in.

Okay – I promised we’d address confounders. This was not a cluster-randomized trial, where some school districts had their mandates removed based on the vicissitudes of a virtual coin flip, as much as many of us would have been interested to see that. The decision to remove masks was up to the various school boards – and they had a lot of pressure on them from many different directions. But all we need to worry about is whether any of those things that pressure a school board to keep masks on would ALSO lead to fewer COVID cases. That’s how confounders work, and how you can get false results in a study like this.

And yes – districts that kept the masks on longer were different than those who took them right off. But check out how they were different.

The districts that kept masks on longer had more low-income students. More Black and Latino students. More students per classroom. These are all risk factors that increase the risk of COVID infection. In other words, the confounding here goes in the opposite direction of the results. If anything, these factors should make you more certain that masking works.

The authors also adjusted for other factors – the community transmission of COVID-19, vaccination rates, school district sizes, and so on. No major change in the results.

One concern I addressed to Dr. Ellie Murray, the biostatistician on the study – could districts that removed masks simply have been testing more to compensate, leading to increased capturing of cases?

If anything, the schools that kept masks on were testing more than the schools that took them off – again that would tend to imply that the results are even stronger than what was reported.

Is this a perfect study? Of course not – it’s one study, it’s from one state. And the relatively large effects from keeping masks on for one or 2 weeks require us to really embrace the concept of exponential growth of infections, but, if COVID has taught us anything, it is that small changes in initial conditions can have pretty big effects.

My daughter, who goes to a public school here in Connecticut, unmasked, was home with COVID this past week. She’s fine. But you know what? She missed a week of school. I worked from home to be with her – though I didn’t test positive. And that is a real cost to both of us that I think we need to consider when we consider the value of masks. Yes, they’re annoying – but if they keep kids in school, might they be worth it? Perhaps not for now, as cases aren’t surging. But in the future, be it a particularly concerning variant, or a whole new pandemic, we should not discount the simple, cheap, and apparently beneficial act of wearing masks to decrease transmission.

Dr. Perry Wilson is an associate professor of medicine and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He disclosed no relevant conflicts of interest.

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

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

On March 26, 2022, Hawaii became the last state in the United States to lift its indoor mask mandate. By the time the current school year started, there were essentially no public school mask mandates either.

Whether you viewed the mask as an emblem of stalwart defiance against a rampaging virus, or a scarlet letter emblematic of the overreaches of public policy, you probably aren’t seeing them much anymore.

And yet, the debate about masks still rages. Who was right, who was wrong? Who trusted science, and what does the science even say? If we brought our country into marriage counseling, would we be told it is time to move on?  To look forward, not backward? To plan for our bright future together?

Perhaps. But this question isn’t really moot just because masks have largely disappeared in the United States. Variants may emerge that lead to more infection waves – and other pandemics may occur in the future. And so I think it is important to discuss a study that, with quite rigorous analysis, attempts to answer the following question: Did masking in schools lower students’ and teachers’ risk of COVID?

We are talking about this study, appearing in the New England Journal of Medicine. The short version goes like this.

Researchers had access to two important sources of data. One – an accounting of all the teachers and students (more than 300,000 of them) in 79 public, noncharter school districts in Eastern Massachusetts who tested positive for COVID every week. Two – the date that each of those school districts lifted their mask mandates or (in the case of two districts) didn’t.

Right away, I’m sure you’re thinking of potential issues. Districts that kept masks even when the statewide ban was lifted are likely quite a bit different from districts that dropped masks right away. You’re right, of course – hold on to that thought; we’ll get there.

But first – the big question – would districts that kept their masks on longer do better when it comes to the rate of COVID infection?

When everyone was masking, COVID case rates were pretty similar. Statewide mandates are lifted in late February – and most school districts remove their mandates within a few weeks – the black line are the two districts (Boston and Chelsea) where mask mandates remained in place.

As time marched on, the case rates in the various districts spread out – with districts that kept masks on longer doing better than those that took them off, and districts that kept masks on the whole time doing best of all.

Prior to the mask mandate lifting, you see very similar COVID rates in districts that would eventually remove the mandate and those that would not, with a bit of noise around the initial Omicron wave which saw just a huge amount of people get infected.

And then, after the mandate was lifted, separation. Districts that held on to masks longer had lower rates of COVID infection.

In all, over the 15-weeks of the study, there were roughly 12,000 extra cases of COVID in the mask-free school districts, which corresponds to about 35% of the total COVID burden during that time. And, yes, kids do well with COVID – on average. But 12,000 extra cases is enough to translate into a significant number of important clinical outcomes – think hospitalizations and post-COVID syndromes. And of course, maybe most importantly, missed school days. Positive kids were not allowed in class no matter what district they were in.

Okay – I promised we’d address confounders. This was not a cluster-randomized trial, where some school districts had their mandates removed based on the vicissitudes of a virtual coin flip, as much as many of us would have been interested to see that. The decision to remove masks was up to the various school boards – and they had a lot of pressure on them from many different directions. But all we need to worry about is whether any of those things that pressure a school board to keep masks on would ALSO lead to fewer COVID cases. That’s how confounders work, and how you can get false results in a study like this.

And yes – districts that kept the masks on longer were different than those who took them right off. But check out how they were different.

The districts that kept masks on longer had more low-income students. More Black and Latino students. More students per classroom. These are all risk factors that increase the risk of COVID infection. In other words, the confounding here goes in the opposite direction of the results. If anything, these factors should make you more certain that masking works.

The authors also adjusted for other factors – the community transmission of COVID-19, vaccination rates, school district sizes, and so on. No major change in the results.

One concern I addressed to Dr. Ellie Murray, the biostatistician on the study – could districts that removed masks simply have been testing more to compensate, leading to increased capturing of cases?

If anything, the schools that kept masks on were testing more than the schools that took them off – again that would tend to imply that the results are even stronger than what was reported.

Is this a perfect study? Of course not – it’s one study, it’s from one state. And the relatively large effects from keeping masks on for one or 2 weeks require us to really embrace the concept of exponential growth of infections, but, if COVID has taught us anything, it is that small changes in initial conditions can have pretty big effects.

My daughter, who goes to a public school here in Connecticut, unmasked, was home with COVID this past week. She’s fine. But you know what? She missed a week of school. I worked from home to be with her – though I didn’t test positive. And that is a real cost to both of us that I think we need to consider when we consider the value of masks. Yes, they’re annoying – but if they keep kids in school, might they be worth it? Perhaps not for now, as cases aren’t surging. But in the future, be it a particularly concerning variant, or a whole new pandemic, we should not discount the simple, cheap, and apparently beneficial act of wearing masks to decrease transmission.

Dr. Perry Wilson is an associate professor of medicine and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He disclosed no relevant conflicts of interest.

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

An epidemiological analysis using genetic data shows that having babies protects women from endometrial cancer.

Compared with having no children, the risk reduction for endometrial cancer was 21% with having one child, 38% with having two, and 51% with having three, Gunn-Helen Moen, MSc, PhD, a research fellow at the University of Queensland Institute for Molecular Bioscience in St. Lucia, Australia, and the senior author of the study, said in an email.

In the United States, the prevalence of endometrial cancer is 25.7 per 100,000 women per year, with a lifetime risk of 2.8%.

Multiple observational studies have linked giving birth to risk of endometrial cancer. For the new study, Dr. Moen and her team assessed various risk factors related to ovulation and reproductive function using Mendelian randomization, an epidemiological technique that deploys genetic variants to detect cause-and-effect relationships between potentially modifiable risk factors and health outcomes in observational data.

The researcher published their findings in BMC Medicine.
 

Leverage genetic data

The study used detailed genetic and health data from the UK Biobank, a databank with more than half a million participants. Genetic variants related to some of the risk factors were used to assess whether the variants make people more likely to develop endometrial cancer.

Genomewide significant single-nucleotide polymorphisms (SNPs) related to number of live births, age at menopause and menarche, and body mass index (BMI) had been identified in previous studies, the researchers reported. They conducted genomewide association analyses of the databank to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.

The MR analysis showed a potential causal effect for the number of live births (inverse variance–weighted odds ratio, 0.537) and number of years ovulating (IVW OR, 1.051), in addition to known risk factors of BMI, age at menarche, and age at menopause.

A further multivariable MR analysis showed that number of births had a negative causal effect on endometrial cancer risk (OR, 0.783), independent of the causal effect of known risk factors such as BMI, age at menarche and age at menopause.

Reported limitations included being unable to perform MR analyses on some factors, such as oral contraceptive use, because of a lack of valid genetic instruments. The researchers could not perform an age adjustment at diagnosis because of a lack of data.

In addition, the genetic data came exclusively from White women of European ancestry.
 

‘A personal choice’

Other investigators have hypothesized that the protective effect of childbirth may be caused by shedding of malignant and premalignant endometrial cells during and after childbirth and exposure to high levels of progesterone in late stages of pregnancy, the research team noted.

Dr. Moen said, based on the results, physicians might consider number of childbirths in assessing a patient’s risk of endometrial cancer.

However, Britton Trabert, MSPH, MS, PhD, an epidemiologist and assistant professor of obstetrics and gynecology at the University of Utah, Salt Lake City, said it’s unlikely the findings will affect clinical practice given that they “largely replicate well-characterized endometrial cancer risk associations.”

“Pregnancy and childbirth are a personal choice and is not largely regarded as a modifiable factor for cancer prevention,” said Dr. Trabert, who was not involved in the study.

The study’s investigators reported funding from the governments of Australia, Norway and the United Kingdom and the British Heart Foundation. No financial conflicts of interest were reported. Dr. Trabert reported no relevant financial interests.

An epidemiological analysis using genetic data shows that having babies protects women from endometrial cancer.

Compared with having no children, the risk reduction for endometrial cancer was 21% with having one child, 38% with having two, and 51% with having three, Gunn-Helen Moen, MSc, PhD, a research fellow at the University of Queensland Institute for Molecular Bioscience in St. Lucia, Australia, and the senior author of the study, said in an email.

In the United States, the prevalence of endometrial cancer is 25.7 per 100,000 women per year, with a lifetime risk of 2.8%.

Multiple observational studies have linked giving birth to risk of endometrial cancer. For the new study, Dr. Moen and her team assessed various risk factors related to ovulation and reproductive function using Mendelian randomization, an epidemiological technique that deploys genetic variants to detect cause-and-effect relationships between potentially modifiable risk factors and health outcomes in observational data.

The researcher published their findings in BMC Medicine.
 

Leverage genetic data

The study used detailed genetic and health data from the UK Biobank, a databank with more than half a million participants. Genetic variants related to some of the risk factors were used to assess whether the variants make people more likely to develop endometrial cancer.

Genomewide significant single-nucleotide polymorphisms (SNPs) related to number of live births, age at menopause and menarche, and body mass index (BMI) had been identified in previous studies, the researchers reported. They conducted genomewide association analyses of the databank to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.

The MR analysis showed a potential causal effect for the number of live births (inverse variance–weighted odds ratio, 0.537) and number of years ovulating (IVW OR, 1.051), in addition to known risk factors of BMI, age at menarche, and age at menopause.

A further multivariable MR analysis showed that number of births had a negative causal effect on endometrial cancer risk (OR, 0.783), independent of the causal effect of known risk factors such as BMI, age at menarche and age at menopause.

Reported limitations included being unable to perform MR analyses on some factors, such as oral contraceptive use, because of a lack of valid genetic instruments. The researchers could not perform an age adjustment at diagnosis because of a lack of data.

In addition, the genetic data came exclusively from White women of European ancestry.
 

‘A personal choice’

Other investigators have hypothesized that the protective effect of childbirth may be caused by shedding of malignant and premalignant endometrial cells during and after childbirth and exposure to high levels of progesterone in late stages of pregnancy, the research team noted.

Dr. Moen said, based on the results, physicians might consider number of childbirths in assessing a patient’s risk of endometrial cancer.

However, Britton Trabert, MSPH, MS, PhD, an epidemiologist and assistant professor of obstetrics and gynecology at the University of Utah, Salt Lake City, said it’s unlikely the findings will affect clinical practice given that they “largely replicate well-characterized endometrial cancer risk associations.”

“Pregnancy and childbirth are a personal choice and is not largely regarded as a modifiable factor for cancer prevention,” said Dr. Trabert, who was not involved in the study.

The study’s investigators reported funding from the governments of Australia, Norway and the United Kingdom and the British Heart Foundation. No financial conflicts of interest were reported. Dr. Trabert reported no relevant financial interests.

An epidemiological analysis using genetic data shows that having babies protects women from endometrial cancer.

Compared with having no children, the risk reduction for endometrial cancer was 21% with having one child, 38% with having two, and 51% with having three, Gunn-Helen Moen, MSc, PhD, a research fellow at the University of Queensland Institute for Molecular Bioscience in St. Lucia, Australia, and the senior author of the study, said in an email.

In the United States, the prevalence of endometrial cancer is 25.7 per 100,000 women per year, with a lifetime risk of 2.8%.

Multiple observational studies have linked giving birth to risk of endometrial cancer. For the new study, Dr. Moen and her team assessed various risk factors related to ovulation and reproductive function using Mendelian randomization, an epidemiological technique that deploys genetic variants to detect cause-and-effect relationships between potentially modifiable risk factors and health outcomes in observational data.

The researcher published their findings in BMC Medicine.
 

Leverage genetic data

The study used detailed genetic and health data from the UK Biobank, a databank with more than half a million participants. Genetic variants related to some of the risk factors were used to assess whether the variants make people more likely to develop endometrial cancer.

Genomewide significant single-nucleotide polymorphisms (SNPs) related to number of live births, age at menopause and menarche, and body mass index (BMI) had been identified in previous studies, the researchers reported. They conducted genomewide association analyses of the databank to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.

The MR analysis showed a potential causal effect for the number of live births (inverse variance–weighted odds ratio, 0.537) and number of years ovulating (IVW OR, 1.051), in addition to known risk factors of BMI, age at menarche, and age at menopause.

A further multivariable MR analysis showed that number of births had a negative causal effect on endometrial cancer risk (OR, 0.783), independent of the causal effect of known risk factors such as BMI, age at menarche and age at menopause.

Reported limitations included being unable to perform MR analyses on some factors, such as oral contraceptive use, because of a lack of valid genetic instruments. The researchers could not perform an age adjustment at diagnosis because of a lack of data.

In addition, the genetic data came exclusively from White women of European ancestry.
 

‘A personal choice’

Other investigators have hypothesized that the protective effect of childbirth may be caused by shedding of malignant and premalignant endometrial cells during and after childbirth and exposure to high levels of progesterone in late stages of pregnancy, the research team noted.

Dr. Moen said, based on the results, physicians might consider number of childbirths in assessing a patient’s risk of endometrial cancer.

However, Britton Trabert, MSPH, MS, PhD, an epidemiologist and assistant professor of obstetrics and gynecology at the University of Utah, Salt Lake City, said it’s unlikely the findings will affect clinical practice given that they “largely replicate well-characterized endometrial cancer risk associations.”

“Pregnancy and childbirth are a personal choice and is not largely regarded as a modifiable factor for cancer prevention,” said Dr. Trabert, who was not involved in the study.

The study’s investigators reported funding from the governments of Australia, Norway and the United Kingdom and the British Heart Foundation. No financial conflicts of interest were reported. Dr. Trabert reported no relevant financial interests.

Understanding of the key mechanisms underlying the progression of type 2 diabetes has been advanced by new research from Oxford (England) University suggesting potential ways to “slow the seemingly inexorable decline in beta-cell function in T2D”.

The study in mice elucidated a “key cause” of T2D by showing that high blood glucose reprograms the metabolism of pancreatic beta-cells, helping to explain the progressive decline in their function in diabetes.

Scientists already knew that chronic hyperglycemia leads to a progressive decline in beta-cell function and, conversely, that the failure of pancreatic beta-cells to produce insulin results in chronically elevated blood glucose. However, the exact cause of beta-cell failure in T2D has remained unclear. T2D typically presents in later adult life, and by the time of diagnosis as much as 50% of beta-cell function has been lost.

In the United Kingdom there are nearly 5 million people diagnosed with T2D, which costs the National Health Service some £10 billion annually.
 

Glucose metabolites, rather than glucose itself, drives failure of cells to release insulin

The new study, published in Nature Communications, used both an animal model of diabetes and in vitro culture of beta-cells in a high glucose medium. In both cases the researchers showed, for the first time, that it is glucose metabolites, rather than glucose itself, that drives the failure of beta-cells to release insulin and is key to the progression of type 2 diabetes. 

Senior researcher Frances Ashcroft, PhD, of the department of physiology, anatomy and genetics at the University of Oxford said: “This suggests a potential way in which the decline in beta-cell function in T2D might be slowed or prevented.”

Blood glucose concentration is controlled within narrow limits, the team explained. When it is too low for more than few minutes, consciousness is rapidly lost because the brain is starved of fuel. However chronic elevation of blood glucose leads to the serious complications found in poorly controlled diabetes, such as retinopathy, nephropathy, peripheral neuropathy, and cardiac disease. Insulin, released from pancreatic beta-cells when blood glucose levels rise, is the only hormone that can lower the blood glucose concentration, and insufficient secretion results in diabetes. In T2D, the beta-cells are still present (unlike in T1D), but they have a reduced insulin content and the coupling between glucose and insulin release is impaired. 
 

Vicious spiral of hyperglycemia and beta-cell damage

Previous work by the same team had shown that chronic hyperglycemia damages the ability of the beta-cell to produce insulin and to release it when blood glucose levels rise. This suggested that “prolonged hyperglycemia sets off a vicious spiral in which an increase in blood glucose leads to beta-cell damage and less insulin secretion - which causes an even greater increase in blood glucose and a further decline in beta-cell function,” the team explained. 

Lead researcher Elizabeth Haythorne, PhD, said: “We realized that we next needed to understand how glucose damages beta-cell function, so we can think about how we might stop it and so slow the seemingly inexorable decline in beta-cell function in T2D.”

In the new study, they showed that altered glycolysis in T2D occurs, in part, through marked up-regulation of mammalian target of rapamycin complex 1 (mTORC1), a protein complex involved in control of cell growth, dysregulation of which underlies a variety of human diseases, including diabetes. Up-regulation of mTORC1 led to changes in metabolic gene expression, oxidative phosphorylation and insulin secretion. Furthermore, they demonstrated that reducing the rate at which glucose is metabolized and at which its metabolites build up could prevent the effects of chronic hyperglycemia and the ensuing beta-cell failure. 

“High blood glucose levels cause an increased rate of glucose metabolism in the beta-cell, which leads to a metabolic bottleneck and the pooling of upstream metabolites,” the team said. “These metabolites switch off the insulin gene, so less insulin is made, as well as switching off numerous genes involved in metabolism and stimulus-secretion coupling. Consequently, the beta-cells become glucose blind and no longer respond to changes in blood glucose with insulin secretion.”
 

Blocking metabolic enzyme could maintain insulin secretion

The team attempted to block the first step in glucose metabolism, and therefore prevent the gene changes from taking place, by blocking the enzyme glucokinase, which regulates the process. They found that this could maintain glucose-stimulated insulin secretion even in the presence of chronic hyperglycemia.

“Our results support the idea that progressive impairment of beta-cell metabolism, induced by increasing hyperglycemia, speeds T2D development, and suggest that reducing glycolysis at the level of glucokinase may slow this progression,” they said.

Dr. Ashcroft said: “This is potentially a useful way to try to prevent beta-cell decline in diabetes. Because glucose metabolism normally stimulates insulin secretion, it was previously hypothesized that increasing glucose metabolism would enhance insulin secretion in T2D and glucokinase activators were trialled, with varying results. 

“Our data suggests that glucokinase activators could have an adverse effect and, somewhat counter-intuitively, that a glucokinase inhibitor might be a better strategy to treat T2D. Of course, it would be important to reduce glucose flux in T2D to that found in people without diabetes – and no further. But there is a very long way to go before we can tell if this approach would be useful for treating beta-cell decline in T2D. 

“In the meantime, the key message from our study if you have type 2 diabetes is that it is important to keep your blood glucose well controlled.”

This study was funded by the UK Medical Research Council, the Biotechnology and Biological Sciences Research Council, the John Fell Fund, and the Nuffield Benefaction for Medicine/Wellcome Institutional Strategic Support Fund. The authors declared no competing interests.

A version of this article first appeared on Medscape UK.

Understanding of the key mechanisms underlying the progression of type 2 diabetes has been advanced by new research from Oxford (England) University suggesting potential ways to “slow the seemingly inexorable decline in beta-cell function in T2D”.

The study in mice elucidated a “key cause” of T2D by showing that high blood glucose reprograms the metabolism of pancreatic beta-cells, helping to explain the progressive decline in their function in diabetes.

Scientists already knew that chronic hyperglycemia leads to a progressive decline in beta-cell function and, conversely, that the failure of pancreatic beta-cells to produce insulin results in chronically elevated blood glucose. However, the exact cause of beta-cell failure in T2D has remained unclear. T2D typically presents in later adult life, and by the time of diagnosis as much as 50% of beta-cell function has been lost.

In the United Kingdom there are nearly 5 million people diagnosed with T2D, which costs the National Health Service some £10 billion annually.
 

Glucose metabolites, rather than glucose itself, drives failure of cells to release insulin

The new study, published in Nature Communications, used both an animal model of diabetes and in vitro culture of beta-cells in a high glucose medium. In both cases the researchers showed, for the first time, that it is glucose metabolites, rather than glucose itself, that drives the failure of beta-cells to release insulin and is key to the progression of type 2 diabetes. 

Senior researcher Frances Ashcroft, PhD, of the department of physiology, anatomy and genetics at the University of Oxford said: “This suggests a potential way in which the decline in beta-cell function in T2D might be slowed or prevented.”

Blood glucose concentration is controlled within narrow limits, the team explained. When it is too low for more than few minutes, consciousness is rapidly lost because the brain is starved of fuel. However chronic elevation of blood glucose leads to the serious complications found in poorly controlled diabetes, such as retinopathy, nephropathy, peripheral neuropathy, and cardiac disease. Insulin, released from pancreatic beta-cells when blood glucose levels rise, is the only hormone that can lower the blood glucose concentration, and insufficient secretion results in diabetes. In T2D, the beta-cells are still present (unlike in T1D), but they have a reduced insulin content and the coupling between glucose and insulin release is impaired. 
 

Vicious spiral of hyperglycemia and beta-cell damage

Previous work by the same team had shown that chronic hyperglycemia damages the ability of the beta-cell to produce insulin and to release it when blood glucose levels rise. This suggested that “prolonged hyperglycemia sets off a vicious spiral in which an increase in blood glucose leads to beta-cell damage and less insulin secretion - which causes an even greater increase in blood glucose and a further decline in beta-cell function,” the team explained. 

Lead researcher Elizabeth Haythorne, PhD, said: “We realized that we next needed to understand how glucose damages beta-cell function, so we can think about how we might stop it and so slow the seemingly inexorable decline in beta-cell function in T2D.”

In the new study, they showed that altered glycolysis in T2D occurs, in part, through marked up-regulation of mammalian target of rapamycin complex 1 (mTORC1), a protein complex involved in control of cell growth, dysregulation of which underlies a variety of human diseases, including diabetes. Up-regulation of mTORC1 led to changes in metabolic gene expression, oxidative phosphorylation and insulin secretion. Furthermore, they demonstrated that reducing the rate at which glucose is metabolized and at which its metabolites build up could prevent the effects of chronic hyperglycemia and the ensuing beta-cell failure. 

“High blood glucose levels cause an increased rate of glucose metabolism in the beta-cell, which leads to a metabolic bottleneck and the pooling of upstream metabolites,” the team said. “These metabolites switch off the insulin gene, so less insulin is made, as well as switching off numerous genes involved in metabolism and stimulus-secretion coupling. Consequently, the beta-cells become glucose blind and no longer respond to changes in blood glucose with insulin secretion.”
 

Blocking metabolic enzyme could maintain insulin secretion

The team attempted to block the first step in glucose metabolism, and therefore prevent the gene changes from taking place, by blocking the enzyme glucokinase, which regulates the process. They found that this could maintain glucose-stimulated insulin secretion even in the presence of chronic hyperglycemia.

“Our results support the idea that progressive impairment of beta-cell metabolism, induced by increasing hyperglycemia, speeds T2D development, and suggest that reducing glycolysis at the level of glucokinase may slow this progression,” they said.

Dr. Ashcroft said: “This is potentially a useful way to try to prevent beta-cell decline in diabetes. Because glucose metabolism normally stimulates insulin secretion, it was previously hypothesized that increasing glucose metabolism would enhance insulin secretion in T2D and glucokinase activators were trialled, with varying results. 

“Our data suggests that glucokinase activators could have an adverse effect and, somewhat counter-intuitively, that a glucokinase inhibitor might be a better strategy to treat T2D. Of course, it would be important to reduce glucose flux in T2D to that found in people without diabetes – and no further. But there is a very long way to go before we can tell if this approach would be useful for treating beta-cell decline in T2D. 

“In the meantime, the key message from our study if you have type 2 diabetes is that it is important to keep your blood glucose well controlled.”

This study was funded by the UK Medical Research Council, the Biotechnology and Biological Sciences Research Council, the John Fell Fund, and the Nuffield Benefaction for Medicine/Wellcome Institutional Strategic Support Fund. The authors declared no competing interests.

A version of this article first appeared on Medscape UK.

Understanding of the key mechanisms underlying the progression of type 2 diabetes has been advanced by new research from Oxford (England) University suggesting potential ways to “slow the seemingly inexorable decline in beta-cell function in T2D”.

The study in mice elucidated a “key cause” of T2D by showing that high blood glucose reprograms the metabolism of pancreatic beta-cells, helping to explain the progressive decline in their function in diabetes.

Scientists already knew that chronic hyperglycemia leads to a progressive decline in beta-cell function and, conversely, that the failure of pancreatic beta-cells to produce insulin results in chronically elevated blood glucose. However, the exact cause of beta-cell failure in T2D has remained unclear. T2D typically presents in later adult life, and by the time of diagnosis as much as 50% of beta-cell function has been lost.

In the United Kingdom there are nearly 5 million people diagnosed with T2D, which costs the National Health Service some £10 billion annually.
 

Glucose metabolites, rather than glucose itself, drives failure of cells to release insulin

The new study, published in Nature Communications, used both an animal model of diabetes and in vitro culture of beta-cells in a high glucose medium. In both cases the researchers showed, for the first time, that it is glucose metabolites, rather than glucose itself, that drives the failure of beta-cells to release insulin and is key to the progression of type 2 diabetes. 

Senior researcher Frances Ashcroft, PhD, of the department of physiology, anatomy and genetics at the University of Oxford said: “This suggests a potential way in which the decline in beta-cell function in T2D might be slowed or prevented.”

Blood glucose concentration is controlled within narrow limits, the team explained. When it is too low for more than few minutes, consciousness is rapidly lost because the brain is starved of fuel. However chronic elevation of blood glucose leads to the serious complications found in poorly controlled diabetes, such as retinopathy, nephropathy, peripheral neuropathy, and cardiac disease. Insulin, released from pancreatic beta-cells when blood glucose levels rise, is the only hormone that can lower the blood glucose concentration, and insufficient secretion results in diabetes. In T2D, the beta-cells are still present (unlike in T1D), but they have a reduced insulin content and the coupling between glucose and insulin release is impaired. 
 

Vicious spiral of hyperglycemia and beta-cell damage

Previous work by the same team had shown that chronic hyperglycemia damages the ability of the beta-cell to produce insulin and to release it when blood glucose levels rise. This suggested that “prolonged hyperglycemia sets off a vicious spiral in which an increase in blood glucose leads to beta-cell damage and less insulin secretion - which causes an even greater increase in blood glucose and a further decline in beta-cell function,” the team explained. 

Lead researcher Elizabeth Haythorne, PhD, said: “We realized that we next needed to understand how glucose damages beta-cell function, so we can think about how we might stop it and so slow the seemingly inexorable decline in beta-cell function in T2D.”

In the new study, they showed that altered glycolysis in T2D occurs, in part, through marked up-regulation of mammalian target of rapamycin complex 1 (mTORC1), a protein complex involved in control of cell growth, dysregulation of which underlies a variety of human diseases, including diabetes. Up-regulation of mTORC1 led to changes in metabolic gene expression, oxidative phosphorylation and insulin secretion. Furthermore, they demonstrated that reducing the rate at which glucose is metabolized and at which its metabolites build up could prevent the effects of chronic hyperglycemia and the ensuing beta-cell failure. 

“High blood glucose levels cause an increased rate of glucose metabolism in the beta-cell, which leads to a metabolic bottleneck and the pooling of upstream metabolites,” the team said. “These metabolites switch off the insulin gene, so less insulin is made, as well as switching off numerous genes involved in metabolism and stimulus-secretion coupling. Consequently, the beta-cells become glucose blind and no longer respond to changes in blood glucose with insulin secretion.”
 

Blocking metabolic enzyme could maintain insulin secretion

The team attempted to block the first step in glucose metabolism, and therefore prevent the gene changes from taking place, by blocking the enzyme glucokinase, which regulates the process. They found that this could maintain glucose-stimulated insulin secretion even in the presence of chronic hyperglycemia.

“Our results support the idea that progressive impairment of beta-cell metabolism, induced by increasing hyperglycemia, speeds T2D development, and suggest that reducing glycolysis at the level of glucokinase may slow this progression,” they said.

Dr. Ashcroft said: “This is potentially a useful way to try to prevent beta-cell decline in diabetes. Because glucose metabolism normally stimulates insulin secretion, it was previously hypothesized that increasing glucose metabolism would enhance insulin secretion in T2D and glucokinase activators were trialled, with varying results. 

“Our data suggests that glucokinase activators could have an adverse effect and, somewhat counter-intuitively, that a glucokinase inhibitor might be a better strategy to treat T2D. Of course, it would be important to reduce glucose flux in T2D to that found in people without diabetes – and no further. But there is a very long way to go before we can tell if this approach would be useful for treating beta-cell decline in T2D. 

“In the meantime, the key message from our study if you have type 2 diabetes is that it is important to keep your blood glucose well controlled.”

This study was funded by the UK Medical Research Council, the Biotechnology and Biological Sciences Research Council, the John Fell Fund, and the Nuffield Benefaction for Medicine/Wellcome Institutional Strategic Support Fund. The authors declared no competing interests.

A version of this article first appeared on Medscape UK.