MANCHESTER, ENGLAND – The use of NSAIDs may mask the true level of inflammation of the sacroiliac joint (SIJ), as seen on MRI, among people with axial spondyloarthritis (axSpA), according to results of the DyNAMISM study.

“We’ve found that in about one in four patients, NSAIDs make a difference to the scan results,” Gareth T. Jones, PhD, said at the annual meeting of the British Society for Rheumatology.

Sara Freeman/MDedge News

A total of 23% of patients whose MRI results were positive for sacroiliitis when no NSAIDs had been used for a couple of weeks received negative MRI results 6 weeks after the NSAIDs were reinstated.

“This is important in terms of diagnosis, in terms of disease classification, and may be important in terms of future treatment decisions,” added Dr. Jones, professor of epidemiology at the Aberdeen Centre for Arthritis and Musculoskeletal Health at the University of Aberdeen, (Scotland).

“Our recommendation from these results is that if a patient is willing to attempt to wash out [NSAIDs] prior to an MRI, we would recommend that they do so,” Dr. Jones said.
 

NSAIDs and AxSpA inflammation

“NSAIDs are often used as the first-line treatment for axial spondyloarthritis due to their ability to effectively reduce pain and stiffness associated with the condition,” Denis Poddubnyy, MD, who was not involved in the research, told this news organization.

“However, there is still a question as to whether NSAIDs have a true anti-inflammatory effect on the axial inflammation, as detected by MRI,” added Dr. Poddubnyy, head of rheumatology at Charité–Universitätsmedizin Berlin in Germany.

With an absence of randomized, controlled trials, it remains “uncertain how much of the observed reduction in inflammation is attributable to the natural course of the disease and spontaneous resolution of inflammation rather than the effect of NSAIDs,” Dr. Poddubnyy said.
 

The DyNAMISM Study

“Sacroiliitis is a painful inflammatory condition. This is investigated looking for the evidence of inflammation on MRI, but many patients are taking anti-inflammatory medication,” Dr. Jones said at the meeting.

“So perhaps patients are taking drugs [that are] hiding the very thing that we’re looking for,” he added. Hence, the DyNAMISM study (Do Nonsteroidal Anti-inflammatory Drugs Mask Inflammation in Spondyloarthritis on MRI) was conceived.

The researchers recruited 311 adults with suspected or established axSpA who were taking daily NSAIDs such as ibuprofen or diclofenac across 34 centers in England and Scotland. Patients taking other anti-inflammatory medications that could not be stopped were excluded, as were patients who were currently taking or had recently taken tumor necrosis factor inhibitors.

The study used a standardized MRI protocol. Two independent readers experienced in scoring SIJ scans were employed; a third was used when the two disagreed. The primary outcome was meeting the Assessment of Spondyloarthritis international Society criteria for a positive result on MRI.

The average age of the study subjects was 42 years, 62% were men, and 87% were White. The median duration of symptoms was 9 years, and the median time since diagnosis was 1 year.

The study design required that patients stop NSAID use over a period of 1-2 weeks before undergoing an MRI scan, which 286 did. Of these, 146 received MRI results that were positive for SIJ inflammation; those patients continued in the study. The 140 patients with negative scans were excluded. Patients could then resume taking NSAIDs before being scanned again around 6 weeks later. In all, 129 patients underwent both MRI scans.
 

How much might fluctuating inflammation matter?

‘It’s a shame you didn’t scan the negative people, because the natural history is a fluctuating inflammation,” Fraser Birrell, MBChB, PhD, of Newcastle University, Newcastle upon Tyne, England, pointed out in discussion.

“Nonsteroidals are modestly effective and probably made no difference,” he argued. “I would have expected a certain proportion of the negatives are positive.”

The study had a pragmatic design, Dr. Jones countered. “We had enormous debate before the study; it would have been nice to do a sort of a randomized, crossover design, but it would have resulted in a lot of inefficiency.”

Regarding the duration of the NSAID washout period, Dr. Jones noted that they saw little difference between shorter or longer washout periods and that the data showed that “a 2-week washout is a reasonable target.”

Performing the second scan 6 weeks after NSAIDs were reinstated “exceeds the period where clinical benefits should be expected. It may be that if we’d waited longer, the proportion would have gone up. So, we would argue that actually, if anything, that 23% may be an underestimate of the real effect.”

Although some patients may have declined to participate in the study because they did not want to stop taking NSAIDs, Dr. Jones noted that a good proportion did stop taking them, and so the study shows that patients can tolerate washout. Around 45% of patients reported experiencing disease flares during this time, but this did not have any significant effect on validated disease activity or pain measures, Dr. Jones reported.

So, if patients are willing to stop NSAIDs before a scan, “they should be counseled that they may experience a small increase in disease activity and spinal pain, but also to be counseled that the majority of patients can tolerate this,” Dr. Jones suggested.

Trials are needed, Dr. Poddubnyy said: “Future randomized, controlled studies are needed to conclusively determine the efficacy of NSAIDs in reducing inflammation in the axial skeleton of axSpA patients.”

Dr. Poddubnyy added: “It would also be valuable to assess in a randomized setting whether the use of NSAIDs impacts the diagnostic performance of MRI, which takes into account not only inflammatory but also structural changes, which are not influenced by NSAIDs.”

The DyNAMISM study was funded by Arthritis Research UK and was run by the University of Aberdeen in conjunction with NHS Grampian, Scotland. Dr. Jones has disclosed no relevant financial relationships. Dr. Poddubnyy disclosed ties with AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Medscape, Merck Sharp & Dohme, Moonlake, Novartis, PeerVoice, Pfizer, Samsung Bioepis, and UCB.

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

MANCHESTER, ENGLAND – The use of NSAIDs may mask the true level of inflammation of the sacroiliac joint (SIJ), as seen on MRI, among people with axial spondyloarthritis (axSpA), according to results of the DyNAMISM study.

“We’ve found that in about one in four patients, NSAIDs make a difference to the scan results,” Gareth T. Jones, PhD, said at the annual meeting of the British Society for Rheumatology.

Sara Freeman/MDedge News

A total of 23% of patients whose MRI results were positive for sacroiliitis when no NSAIDs had been used for a couple of weeks received negative MRI results 6 weeks after the NSAIDs were reinstated.

“This is important in terms of diagnosis, in terms of disease classification, and may be important in terms of future treatment decisions,” added Dr. Jones, professor of epidemiology at the Aberdeen Centre for Arthritis and Musculoskeletal Health at the University of Aberdeen, (Scotland).

“Our recommendation from these results is that if a patient is willing to attempt to wash out [NSAIDs] prior to an MRI, we would recommend that they do so,” Dr. Jones said.
 

NSAIDs and AxSpA inflammation

“NSAIDs are often used as the first-line treatment for axial spondyloarthritis due to their ability to effectively reduce pain and stiffness associated with the condition,” Denis Poddubnyy, MD, who was not involved in the research, told this news organization.

“However, there is still a question as to whether NSAIDs have a true anti-inflammatory effect on the axial inflammation, as detected by MRI,” added Dr. Poddubnyy, head of rheumatology at Charité–Universitätsmedizin Berlin in Germany.

With an absence of randomized, controlled trials, it remains “uncertain how much of the observed reduction in inflammation is attributable to the natural course of the disease and spontaneous resolution of inflammation rather than the effect of NSAIDs,” Dr. Poddubnyy said.
 

The DyNAMISM Study

“Sacroiliitis is a painful inflammatory condition. This is investigated looking for the evidence of inflammation on MRI, but many patients are taking anti-inflammatory medication,” Dr. Jones said at the meeting.

“So perhaps patients are taking drugs [that are] hiding the very thing that we’re looking for,” he added. Hence, the DyNAMISM study (Do Nonsteroidal Anti-inflammatory Drugs Mask Inflammation in Spondyloarthritis on MRI) was conceived.

The researchers recruited 311 adults with suspected or established axSpA who were taking daily NSAIDs such as ibuprofen or diclofenac across 34 centers in England and Scotland. Patients taking other anti-inflammatory medications that could not be stopped were excluded, as were patients who were currently taking or had recently taken tumor necrosis factor inhibitors.

The study used a standardized MRI protocol. Two independent readers experienced in scoring SIJ scans were employed; a third was used when the two disagreed. The primary outcome was meeting the Assessment of Spondyloarthritis international Society criteria for a positive result on MRI.

The average age of the study subjects was 42 years, 62% were men, and 87% were White. The median duration of symptoms was 9 years, and the median time since diagnosis was 1 year.

The study design required that patients stop NSAID use over a period of 1-2 weeks before undergoing an MRI scan, which 286 did. Of these, 146 received MRI results that were positive for SIJ inflammation; those patients continued in the study. The 140 patients with negative scans were excluded. Patients could then resume taking NSAIDs before being scanned again around 6 weeks later. In all, 129 patients underwent both MRI scans.
 

How much might fluctuating inflammation matter?

‘It’s a shame you didn’t scan the negative people, because the natural history is a fluctuating inflammation,” Fraser Birrell, MBChB, PhD, of Newcastle University, Newcastle upon Tyne, England, pointed out in discussion.

“Nonsteroidals are modestly effective and probably made no difference,” he argued. “I would have expected a certain proportion of the negatives are positive.”

The study had a pragmatic design, Dr. Jones countered. “We had enormous debate before the study; it would have been nice to do a sort of a randomized, crossover design, but it would have resulted in a lot of inefficiency.”

Regarding the duration of the NSAID washout period, Dr. Jones noted that they saw little difference between shorter or longer washout periods and that the data showed that “a 2-week washout is a reasonable target.”

Performing the second scan 6 weeks after NSAIDs were reinstated “exceeds the period where clinical benefits should be expected. It may be that if we’d waited longer, the proportion would have gone up. So, we would argue that actually, if anything, that 23% may be an underestimate of the real effect.”

Although some patients may have declined to participate in the study because they did not want to stop taking NSAIDs, Dr. Jones noted that a good proportion did stop taking them, and so the study shows that patients can tolerate washout. Around 45% of patients reported experiencing disease flares during this time, but this did not have any significant effect on validated disease activity or pain measures, Dr. Jones reported.

So, if patients are willing to stop NSAIDs before a scan, “they should be counseled that they may experience a small increase in disease activity and spinal pain, but also to be counseled that the majority of patients can tolerate this,” Dr. Jones suggested.

Trials are needed, Dr. Poddubnyy said: “Future randomized, controlled studies are needed to conclusively determine the efficacy of NSAIDs in reducing inflammation in the axial skeleton of axSpA patients.”

Dr. Poddubnyy added: “It would also be valuable to assess in a randomized setting whether the use of NSAIDs impacts the diagnostic performance of MRI, which takes into account not only inflammatory but also structural changes, which are not influenced by NSAIDs.”

The DyNAMISM study was funded by Arthritis Research UK and was run by the University of Aberdeen in conjunction with NHS Grampian, Scotland. Dr. Jones has disclosed no relevant financial relationships. Dr. Poddubnyy disclosed ties with AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Medscape, Merck Sharp & Dohme, Moonlake, Novartis, PeerVoice, Pfizer, Samsung Bioepis, and UCB.

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

MANCHESTER, ENGLAND – The use of NSAIDs may mask the true level of inflammation of the sacroiliac joint (SIJ), as seen on MRI, among people with axial spondyloarthritis (axSpA), according to results of the DyNAMISM study.

“We’ve found that in about one in four patients, NSAIDs make a difference to the scan results,” Gareth T. Jones, PhD, said at the annual meeting of the British Society for Rheumatology.

Sara Freeman/MDedge News

A total of 23% of patients whose MRI results were positive for sacroiliitis when no NSAIDs had been used for a couple of weeks received negative MRI results 6 weeks after the NSAIDs were reinstated.

“This is important in terms of diagnosis, in terms of disease classification, and may be important in terms of future treatment decisions,” added Dr. Jones, professor of epidemiology at the Aberdeen Centre for Arthritis and Musculoskeletal Health at the University of Aberdeen, (Scotland).

“Our recommendation from these results is that if a patient is willing to attempt to wash out [NSAIDs] prior to an MRI, we would recommend that they do so,” Dr. Jones said.
 

NSAIDs and AxSpA inflammation

“NSAIDs are often used as the first-line treatment for axial spondyloarthritis due to their ability to effectively reduce pain and stiffness associated with the condition,” Denis Poddubnyy, MD, who was not involved in the research, told this news organization.

“However, there is still a question as to whether NSAIDs have a true anti-inflammatory effect on the axial inflammation, as detected by MRI,” added Dr. Poddubnyy, head of rheumatology at Charité–Universitätsmedizin Berlin in Germany.

With an absence of randomized, controlled trials, it remains “uncertain how much of the observed reduction in inflammation is attributable to the natural course of the disease and spontaneous resolution of inflammation rather than the effect of NSAIDs,” Dr. Poddubnyy said.
 

The DyNAMISM Study

“Sacroiliitis is a painful inflammatory condition. This is investigated looking for the evidence of inflammation on MRI, but many patients are taking anti-inflammatory medication,” Dr. Jones said at the meeting.

“So perhaps patients are taking drugs [that are] hiding the very thing that we’re looking for,” he added. Hence, the DyNAMISM study (Do Nonsteroidal Anti-inflammatory Drugs Mask Inflammation in Spondyloarthritis on MRI) was conceived.

The researchers recruited 311 adults with suspected or established axSpA who were taking daily NSAIDs such as ibuprofen or diclofenac across 34 centers in England and Scotland. Patients taking other anti-inflammatory medications that could not be stopped were excluded, as were patients who were currently taking or had recently taken tumor necrosis factor inhibitors.

The study used a standardized MRI protocol. Two independent readers experienced in scoring SIJ scans were employed; a third was used when the two disagreed. The primary outcome was meeting the Assessment of Spondyloarthritis international Society criteria for a positive result on MRI.

The average age of the study subjects was 42 years, 62% were men, and 87% were White. The median duration of symptoms was 9 years, and the median time since diagnosis was 1 year.

The study design required that patients stop NSAID use over a period of 1-2 weeks before undergoing an MRI scan, which 286 did. Of these, 146 received MRI results that were positive for SIJ inflammation; those patients continued in the study. The 140 patients with negative scans were excluded. Patients could then resume taking NSAIDs before being scanned again around 6 weeks later. In all, 129 patients underwent both MRI scans.
 

How much might fluctuating inflammation matter?

‘It’s a shame you didn’t scan the negative people, because the natural history is a fluctuating inflammation,” Fraser Birrell, MBChB, PhD, of Newcastle University, Newcastle upon Tyne, England, pointed out in discussion.

“Nonsteroidals are modestly effective and probably made no difference,” he argued. “I would have expected a certain proportion of the negatives are positive.”

The study had a pragmatic design, Dr. Jones countered. “We had enormous debate before the study; it would have been nice to do a sort of a randomized, crossover design, but it would have resulted in a lot of inefficiency.”

Regarding the duration of the NSAID washout period, Dr. Jones noted that they saw little difference between shorter or longer washout periods and that the data showed that “a 2-week washout is a reasonable target.”

Performing the second scan 6 weeks after NSAIDs were reinstated “exceeds the period where clinical benefits should be expected. It may be that if we’d waited longer, the proportion would have gone up. So, we would argue that actually, if anything, that 23% may be an underestimate of the real effect.”

Although some patients may have declined to participate in the study because they did not want to stop taking NSAIDs, Dr. Jones noted that a good proportion did stop taking them, and so the study shows that patients can tolerate washout. Around 45% of patients reported experiencing disease flares during this time, but this did not have any significant effect on validated disease activity or pain measures, Dr. Jones reported.

So, if patients are willing to stop NSAIDs before a scan, “they should be counseled that they may experience a small increase in disease activity and spinal pain, but also to be counseled that the majority of patients can tolerate this,” Dr. Jones suggested.

Trials are needed, Dr. Poddubnyy said: “Future randomized, controlled studies are needed to conclusively determine the efficacy of NSAIDs in reducing inflammation in the axial skeleton of axSpA patients.”

Dr. Poddubnyy added: “It would also be valuable to assess in a randomized setting whether the use of NSAIDs impacts the diagnostic performance of MRI, which takes into account not only inflammatory but also structural changes, which are not influenced by NSAIDs.”

The DyNAMISM study was funded by Arthritis Research UK and was run by the University of Aberdeen in conjunction with NHS Grampian, Scotland. Dr. Jones has disclosed no relevant financial relationships. Dr. Poddubnyy disclosed ties with AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Medscape, Merck Sharp & Dohme, Moonlake, Novartis, PeerVoice, Pfizer, Samsung Bioepis, and UCB.

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

An investigational outpatient endoscopic procedure may help eliminate the need for insulin in people with type 2 diabetes, early research suggests.

Called recellularization via electroporation therapy (ReCET), the technology, manufactured by Endogenex, uses a specialized catheter to deliver alternating electric pulses to the duodenum to induce cellular regeneration. This process is thought to improve insulin sensitivity, in part, by altering gut hormones and nutritional sensing, principal investigator Jacques Bergman, MD, PhD, said in a press briefing held in conjunction with the annual Digestive Disease Week® (DDW), where he will present the data on May 9.

In the first-in-human study of ReCET, 12 of 14 patients were able to come off insulin for up to a year following the procedure when combined with the use of the glucagonlike peptide–1 agonist semaglutide.

“This might be a game changer in the management of type 2 diabetes because a single outpatient endoscopic intervention was suggested to have a pretty long therapeutic effect, which is compliance-free, as opposed to drug therapy that relies on patients taking the drugs on a daily basis,” said Dr. Bergman, professor of gastrointestinal endoscopy at Amsterdam University Medical Center.

Moreover, he added, “this technique is disease-modifying, so it goes to the root cause of type 2 diabetes and tackles the insulin resistance, as opposed to drug therapy, which at best, is disease-controlling, and the effect is immediately gone if you stop the medication.”

ReCET is similar to another product, Fractyl’s Revita DMR, for which Dr. Bergman was involved in a randomized clinical trial. He said in an interview that the two technologies differ in that the Revita uses heat with submucosal lifting to avoid deeper heat penetration, whereas ReCET is nonthermal. He is also involved in a second randomized trial of the Revita.
 

Is semaglutide muddying the findings?

Asked to comment about the current study with ReCET, Ali Aminian, MD, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic, said that the treatment effect is certainly plausible.

“The observation that hyperglycemia rapidly and substantially improves after bariatric surgery has prompted innovators to search for novel endoscopic procedures targeting the GI tract to improve diabetes and metabolic disease. Over the years, we learned that in addition to its role in digestion and absorption, the GI tract is actually a large endocrine organ which contributes to development of diabetes and metabolic disease.”

However, Dr. Aminian said that, “while these preliminary findings on a very small number of patients with a very short follow-up time are interesting,” he faulted the study design for including semaglutide. “When patients are treated with a combination of therapies, it will be hard to understand the true effect of each therapy,” and particularly, “when we add a strong diabetes medication like semaglutide.”

Dr. Bergman said semaglutide was used to “boost the insulin-resistant effect of the endoscopic treatment,” and that a planned double-blind, randomized trial will “show how much semaglutide actually contributed to the effect.” The ultimate goal, he noted, is to eliminate the need for all medications.

Moreover, when people with type 2 diabetes add semaglutide to insulin treatment, only about 20% typically are able to quit taking the insulin, in contrast to the 86% seen in this study, lead author Celine Busch, MBBS, a PhD candidate in gastroenterology at Amsterdam University, said in a DDW statement.

Dr. Aminian said, “I’m looking forward to better quality data ... from studies with a stronger design to prove safety, efficacy, and durability of this endoscopic intervention in patients with diabetes.”

But, he also cautioned, “in the past few years, other endoscopic procedures targeting the duodenum were introduced with exciting initial findings based on a small series [with a] short-term follow-up time. However, their safety, efficacy, and durability were not proven in subsequent studies.”
 

All patients stopped insulin, most for a year

The single-arm, single-center study involved 14 patients with type 2 diabetes taking basal but not premeal insulin. All underwent the 1-hour outpatient ReCET procedure, which involved placing a catheter into the first part of the small bowel and delivering electrical pulses to the duodenum.

Patients adhered to a calorie-controlled liquid diet for 2 weeks, after which they were initiated on semaglutide. All 14 patients were able to come off insulin for 3 months while maintaining glycemic control, and 12 were able to come off insulin for 12 months. They also experienced a 50% reduction in liver fat.

Dr. Bergman said a randomized, double-blind study using a sham procedure for controls is expected to start in about 2 months. “But for now, we are very encouraged by the potential for controlling type 2 diabetes with a single endoscopic treatment.”

Dr. Bergman has reported serving on the advisory board for Endogenex. Dr. Aminian has reported receiving research support and honorarium from Medtronic and Ethicon.

The meeting is sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

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

An investigational outpatient endoscopic procedure may help eliminate the need for insulin in people with type 2 diabetes, early research suggests.

Called recellularization via electroporation therapy (ReCET), the technology, manufactured by Endogenex, uses a specialized catheter to deliver alternating electric pulses to the duodenum to induce cellular regeneration. This process is thought to improve insulin sensitivity, in part, by altering gut hormones and nutritional sensing, principal investigator Jacques Bergman, MD, PhD, said in a press briefing held in conjunction with the annual Digestive Disease Week® (DDW), where he will present the data on May 9.

In the first-in-human study of ReCET, 12 of 14 patients were able to come off insulin for up to a year following the procedure when combined with the use of the glucagonlike peptide–1 agonist semaglutide.

“This might be a game changer in the management of type 2 diabetes because a single outpatient endoscopic intervention was suggested to have a pretty long therapeutic effect, which is compliance-free, as opposed to drug therapy that relies on patients taking the drugs on a daily basis,” said Dr. Bergman, professor of gastrointestinal endoscopy at Amsterdam University Medical Center.

Moreover, he added, “this technique is disease-modifying, so it goes to the root cause of type 2 diabetes and tackles the insulin resistance, as opposed to drug therapy, which at best, is disease-controlling, and the effect is immediately gone if you stop the medication.”

ReCET is similar to another product, Fractyl’s Revita DMR, for which Dr. Bergman was involved in a randomized clinical trial. He said in an interview that the two technologies differ in that the Revita uses heat with submucosal lifting to avoid deeper heat penetration, whereas ReCET is nonthermal. He is also involved in a second randomized trial of the Revita.
 

Is semaglutide muddying the findings?

Asked to comment about the current study with ReCET, Ali Aminian, MD, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic, said that the treatment effect is certainly plausible.

“The observation that hyperglycemia rapidly and substantially improves after bariatric surgery has prompted innovators to search for novel endoscopic procedures targeting the GI tract to improve diabetes and metabolic disease. Over the years, we learned that in addition to its role in digestion and absorption, the GI tract is actually a large endocrine organ which contributes to development of diabetes and metabolic disease.”

However, Dr. Aminian said that, “while these preliminary findings on a very small number of patients with a very short follow-up time are interesting,” he faulted the study design for including semaglutide. “When patients are treated with a combination of therapies, it will be hard to understand the true effect of each therapy,” and particularly, “when we add a strong diabetes medication like semaglutide.”

Dr. Bergman said semaglutide was used to “boost the insulin-resistant effect of the endoscopic treatment,” and that a planned double-blind, randomized trial will “show how much semaglutide actually contributed to the effect.” The ultimate goal, he noted, is to eliminate the need for all medications.

Moreover, when people with type 2 diabetes add semaglutide to insulin treatment, only about 20% typically are able to quit taking the insulin, in contrast to the 86% seen in this study, lead author Celine Busch, MBBS, a PhD candidate in gastroenterology at Amsterdam University, said in a DDW statement.

Dr. Aminian said, “I’m looking forward to better quality data ... from studies with a stronger design to prove safety, efficacy, and durability of this endoscopic intervention in patients with diabetes.”

But, he also cautioned, “in the past few years, other endoscopic procedures targeting the duodenum were introduced with exciting initial findings based on a small series [with a] short-term follow-up time. However, their safety, efficacy, and durability were not proven in subsequent studies.”
 

All patients stopped insulin, most for a year

The single-arm, single-center study involved 14 patients with type 2 diabetes taking basal but not premeal insulin. All underwent the 1-hour outpatient ReCET procedure, which involved placing a catheter into the first part of the small bowel and delivering electrical pulses to the duodenum.

Patients adhered to a calorie-controlled liquid diet for 2 weeks, after which they were initiated on semaglutide. All 14 patients were able to come off insulin for 3 months while maintaining glycemic control, and 12 were able to come off insulin for 12 months. They also experienced a 50% reduction in liver fat.

Dr. Bergman said a randomized, double-blind study using a sham procedure for controls is expected to start in about 2 months. “But for now, we are very encouraged by the potential for controlling type 2 diabetes with a single endoscopic treatment.”

Dr. Bergman has reported serving on the advisory board for Endogenex. Dr. Aminian has reported receiving research support and honorarium from Medtronic and Ethicon.

The meeting is sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

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

An investigational outpatient endoscopic procedure may help eliminate the need for insulin in people with type 2 diabetes, early research suggests.

Called recellularization via electroporation therapy (ReCET), the technology, manufactured by Endogenex, uses a specialized catheter to deliver alternating electric pulses to the duodenum to induce cellular regeneration. This process is thought to improve insulin sensitivity, in part, by altering gut hormones and nutritional sensing, principal investigator Jacques Bergman, MD, PhD, said in a press briefing held in conjunction with the annual Digestive Disease Week® (DDW), where he will present the data on May 9.

In the first-in-human study of ReCET, 12 of 14 patients were able to come off insulin for up to a year following the procedure when combined with the use of the glucagonlike peptide–1 agonist semaglutide.

“This might be a game changer in the management of type 2 diabetes because a single outpatient endoscopic intervention was suggested to have a pretty long therapeutic effect, which is compliance-free, as opposed to drug therapy that relies on patients taking the drugs on a daily basis,” said Dr. Bergman, professor of gastrointestinal endoscopy at Amsterdam University Medical Center.

Moreover, he added, “this technique is disease-modifying, so it goes to the root cause of type 2 diabetes and tackles the insulin resistance, as opposed to drug therapy, which at best, is disease-controlling, and the effect is immediately gone if you stop the medication.”

ReCET is similar to another product, Fractyl’s Revita DMR, for which Dr. Bergman was involved in a randomized clinical trial. He said in an interview that the two technologies differ in that the Revita uses heat with submucosal lifting to avoid deeper heat penetration, whereas ReCET is nonthermal. He is also involved in a second randomized trial of the Revita.
 

Is semaglutide muddying the findings?

Asked to comment about the current study with ReCET, Ali Aminian, MD, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic, said that the treatment effect is certainly plausible.

“The observation that hyperglycemia rapidly and substantially improves after bariatric surgery has prompted innovators to search for novel endoscopic procedures targeting the GI tract to improve diabetes and metabolic disease. Over the years, we learned that in addition to its role in digestion and absorption, the GI tract is actually a large endocrine organ which contributes to development of diabetes and metabolic disease.”

However, Dr. Aminian said that, “while these preliminary findings on a very small number of patients with a very short follow-up time are interesting,” he faulted the study design for including semaglutide. “When patients are treated with a combination of therapies, it will be hard to understand the true effect of each therapy,” and particularly, “when we add a strong diabetes medication like semaglutide.”

Dr. Bergman said semaglutide was used to “boost the insulin-resistant effect of the endoscopic treatment,” and that a planned double-blind, randomized trial will “show how much semaglutide actually contributed to the effect.” The ultimate goal, he noted, is to eliminate the need for all medications.

Moreover, when people with type 2 diabetes add semaglutide to insulin treatment, only about 20% typically are able to quit taking the insulin, in contrast to the 86% seen in this study, lead author Celine Busch, MBBS, a PhD candidate in gastroenterology at Amsterdam University, said in a DDW statement.

Dr. Aminian said, “I’m looking forward to better quality data ... from studies with a stronger design to prove safety, efficacy, and durability of this endoscopic intervention in patients with diabetes.”

But, he also cautioned, “in the past few years, other endoscopic procedures targeting the duodenum were introduced with exciting initial findings based on a small series [with a] short-term follow-up time. However, their safety, efficacy, and durability were not proven in subsequent studies.”
 

All patients stopped insulin, most for a year

The single-arm, single-center study involved 14 patients with type 2 diabetes taking basal but not premeal insulin. All underwent the 1-hour outpatient ReCET procedure, which involved placing a catheter into the first part of the small bowel and delivering electrical pulses to the duodenum.

Patients adhered to a calorie-controlled liquid diet for 2 weeks, after which they were initiated on semaglutide. All 14 patients were able to come off insulin for 3 months while maintaining glycemic control, and 12 were able to come off insulin for 12 months. They also experienced a 50% reduction in liver fat.

Dr. Bergman said a randomized, double-blind study using a sham procedure for controls is expected to start in about 2 months. “But for now, we are very encouraged by the potential for controlling type 2 diabetes with a single endoscopic treatment.”

Dr. Bergman has reported serving on the advisory board for Endogenex. Dr. Aminian has reported receiving research support and honorarium from Medtronic and Ethicon.

The meeting is sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

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

In September 2021, a community in Virginia experienced an outbreak of hepatitis A virus (HAV) that was ultimately linked to an infected food handler.¹ A total of 149 cases were reported over the next 12 months; 51 were directly related to the food handler and the remainder were the result of sustained community transmission. Of the 51 people who were directly infected by the food handler, 31 were hospitalized and 3 died. This incident offers important reminders about public health surveillance and the role that family physicians can play.

Hepatitis A virus is transmitted through food and drinks that have been contaminated by small amounts of stool that contains the virus or through close contact (including sexual contact) with a person who is infected. The incubation period can range from 15 to 59 days.

HAV generally resolves in a few days to weeks, with no long-term effects. However, recent outbreaks have been associated with high hospitalization and mortality rates because of the underlying comorbidities of those infected.

An increase in incidence. The national rate of HAV infection reached a low of less than 1/100,000 in 2015 but has since increased to almost 6/100,000 in 2019. This increase is mostly due to outbreaks linked to spread among people without a fixed residence, those who use illicit drugs, and men who have sex with men.²

In the Virginia outbreak, the food handler had a risk factor for HAV and was unvaccinated. He worked at 3 different locations of a restaurant chain for a total of 16 days while infectious, preparing ready-to-eat food without using gloves. Furthermore, he delayed seeking medical care for more than 2 weeks—at which time, the nature of his employment was not disclosed.

Prevention is straightforward. HAV infection can be prevented by administration of either HAV vaccine or immune globulin within 2 weeks of exposure.³ During an HAV outbreak, vaccination is recommended for people considered to be at risk, including those without a fixed residence, those who use illicit drugs, those who travel internationally, and men who have sex with men.³

There are 3 HAV vaccines available in the United States: 2 single-antigen vaccines, Havrix and Vaqta, both approved for children and adults, and a combination vaccine (containing both HAV and hepatitis B antigens), Twinrix, which is approved for those ages 18 years and older. All are inactivated vaccines.

What you can do. The Virginia outbreak illustrates the important role that family physicians can and do play in public health. We should:

• Encourage adults with risk factors for HAV to be vaccinated.
• Ask those with an HAV diagnosis about the people they may have exposed through personal contact or occupational exposure.
• Promptly report infectious diseases that are designated “reportable” to the public health department.
• Immediately report (by telephone) when HAV and other enteric infections involve a food handler.

In September 2021, a community in Virginia experienced an outbreak of hepatitis A virus (HAV) that was ultimately linked to an infected food handler.¹ A total of 149 cases were reported over the next 12 months; 51 were directly related to the food handler and the remainder were the result of sustained community transmission. Of the 51 people who were directly infected by the food handler, 31 were hospitalized and 3 died. This incident offers important reminders about public health surveillance and the role that family physicians can play.

Hepatitis A virus is transmitted through food and drinks that have been contaminated by small amounts of stool that contains the virus or through close contact (including sexual contact) with a person who is infected. The incubation period can range from 15 to 59 days.

HAV generally resolves in a few days to weeks, with no long-term effects. However, recent outbreaks have been associated with high hospitalization and mortality rates because of the underlying comorbidities of those infected.

An increase in incidence. The national rate of HAV infection reached a low of less than 1/100,000 in 2015 but has since increased to almost 6/100,000 in 2019. This increase is mostly due to outbreaks linked to spread among people without a fixed residence, those who use illicit drugs, and men who have sex with men.²

In the Virginia outbreak, the food handler had a risk factor for HAV and was unvaccinated. He worked at 3 different locations of a restaurant chain for a total of 16 days while infectious, preparing ready-to-eat food without using gloves. Furthermore, he delayed seeking medical care for more than 2 weeks—at which time, the nature of his employment was not disclosed.

Prevention is straightforward. HAV infection can be prevented by administration of either HAV vaccine or immune globulin within 2 weeks of exposure.³ During an HAV outbreak, vaccination is recommended for people considered to be at risk, including those without a fixed residence, those who use illicit drugs, those who travel internationally, and men who have sex with men.³

There are 3 HAV vaccines available in the United States: 2 single-antigen vaccines, Havrix and Vaqta, both approved for children and adults, and a combination vaccine (containing both HAV and hepatitis B antigens), Twinrix, which is approved for those ages 18 years and older. All are inactivated vaccines.

What you can do. The Virginia outbreak illustrates the important role that family physicians can and do play in public health. We should:

• Encourage adults with risk factors for HAV to be vaccinated.
• Ask those with an HAV diagnosis about the people they may have exposed through personal contact or occupational exposure.
• Promptly report infectious diseases that are designated “reportable” to the public health department.
• Immediately report (by telephone) when HAV and other enteric infections involve a food handler.

In September 2021, a community in Virginia experienced an outbreak of hepatitis A virus (HAV) that was ultimately linked to an infected food handler.¹ A total of 149 cases were reported over the next 12 months; 51 were directly related to the food handler and the remainder were the result of sustained community transmission. Of the 51 people who were directly infected by the food handler, 31 were hospitalized and 3 died. This incident offers important reminders about public health surveillance and the role that family physicians can play.

Hepatitis A virus is transmitted through food and drinks that have been contaminated by small amounts of stool that contains the virus or through close contact (including sexual contact) with a person who is infected. The incubation period can range from 15 to 59 days.

HAV generally resolves in a few days to weeks, with no long-term effects. However, recent outbreaks have been associated with high hospitalization and mortality rates because of the underlying comorbidities of those infected.

An increase in incidence. The national rate of HAV infection reached a low of less than 1/100,000 in 2015 but has since increased to almost 6/100,000 in 2019. This increase is mostly due to outbreaks linked to spread among people without a fixed residence, those who use illicit drugs, and men who have sex with men.²

In the Virginia outbreak, the food handler had a risk factor for HAV and was unvaccinated. He worked at 3 different locations of a restaurant chain for a total of 16 days while infectious, preparing ready-to-eat food without using gloves. Furthermore, he delayed seeking medical care for more than 2 weeks—at which time, the nature of his employment was not disclosed.

Prevention is straightforward. HAV infection can be prevented by administration of either HAV vaccine or immune globulin within 2 weeks of exposure.³ During an HAV outbreak, vaccination is recommended for people considered to be at risk, including those without a fixed residence, those who use illicit drugs, those who travel internationally, and men who have sex with men.³

There are 3 HAV vaccines available in the United States: 2 single-antigen vaccines, Havrix and Vaqta, both approved for children and adults, and a combination vaccine (containing both HAV and hepatitis B antigens), Twinrix, which is approved for those ages 18 years and older. All are inactivated vaccines.

What you can do. The Virginia outbreak illustrates the important role that family physicians can and do play in public health. We should:

• Encourage adults with risk factors for HAV to be vaccinated.
• Ask those with an HAV diagnosis about the people they may have exposed through personal contact or occupational exposure.
• Promptly report infectious diseases that are designated “reportable” to the public health department.
• Immediately report (by telephone) when HAV and other enteric infections involve a food handler.

The first guideline for definitive local therapy options in the treatment of oligometastatic non–small cell lung cancer (NSCLC) has now been released.

The result of a joint effort by the American Society for Radiation Oncology and European Society for Radiotherapy and Oncology, the guidelines emphasizes the need for a multidisciplinary team approach to guide treatment decisions for oligometastatic disease.

Historically, treatment for oligometastatic NSCLC has involved systemic therapy including chemotherapy or immunotherapy, and local therapy was given only for palliation and symptom relief. But increasing evidence has demonstrated that definitive local therapy may have an additional role in controlling tumor growth and improving survival outcomes, and an increasing number of radiation oncologists and multidisciplinary teams are now using local therapy beyond palliative care for these patients, the authors noted.

“Oligometastatic NSCLC is a phase in lung cancer development that may offer us new opportunities to improve patient outcomes, because it typically is more treatable than widely metastatic cancer,” said Puneeth Iyengar, MD, PhD, cochair of the guideline task force and an associate professor of radiation oncology at UT Southwestern Medical Center, Dallas.

“The research on local therapy for oligometastatic cancer is still at a relatively early stage, but we already see indicators of potential benefits for patients. Adding local therapy to systemic therapy may lead to more durable cancer control, potentially improving progression-free survival, overall survival and quality of life,” he said in a statement.

The new guideline is published in Practical Radiation Oncology.

The purpose of this joint guideline was to provide recommendations on local therapy use for oligometastatic NSCLC, along with a summary of the evidence justifying its incorporation into standard treatment paradigms.
 

Key recommendations

Owing to the lack of significant randomized phase 3 trials, the guideline task force strongly recommended a patient-centered, multidisciplinary approach for all decision-making regarding potential treatment. In addition, algorithms were also created for the optimal clinical scenarios for local therapy and the different types of local therapy that are available for these patients.

Key recommendations include:

• The integration of definitive local therapy is recommended only for patients who have five or fewer distant extracranial metastases, and only when technically feasible and clinically safe for all disease sites. Definitive local therapy is also conditionally recommended for carefully selected patients with synchronous oligometastatic, metachronous oligorecurrent, induced oligopersistent, or induced oligoprogressive conditions for extracranial NSCLC.
• Radiation and surgery are the only recommended modalities for definitive local treatment of oligometastatic NSCLC. Radiation is favored when multiple organ systems are being treated or when the clinical priority is to minimize breaks from systemic therapy, whereas surgery is favored when large tissue sampling is needed for molecular testing to guide systemic therapy.
• For sequencing and timing, there is an emphasis on upfront, definitive local treatment for symptomatic metastases. For asymptomatic patients with synchronous disease, at least 3 months of standard-of-care systemic therapy is recommended before starting definitive local therapy.
• For optimal staging, radiation dosing, treatment planning, and delivery techniques, there is a preference for hypofractionated radiation therapy or stereotactic body radiation therapy when appropriate. The task force also emphasizes the importance of appropriate imaging and comments that it “cannot be overstated” to diagnose oligometastatic disease; they recommend that care teams consult guidelines from groups such as the National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer.
• Patients who develop disease progression at a limited number of sites, so-called oligoprogression at previously treated sites, and/or de novo recurrences at new sites may benefit from repeat local definitive therapy performed with the aim of prolonging progression-free survival or delaying a switch in systemic therapies.

Matthias Guckenberger, MD, cochair of the guideline task force and a professor and chairman of radiation oncology at the University Hospital Zürich, cautioned that “despite the widespread enthusiasm in the field of oligometastatic disease, the quality of evidence supporting the integration of definitive local therapy into a multimodality treatment strategy is still lower as compared to indications such as locally advanced NSCLC.”

“To compensate for this lack of highest-quality evidence, recommendations of this guideline were established by a broad consensus involving experts from ASTRO and ESTRO, colleagues from the fields of thoracic surgery and medical oncology and a patient representative,” Dr. Guckenberger said in a statement.

The guideline task force also emphasized the need for equitable use of these techniques, noting that “a significant effort must be taken to ensure that the decisions regarding the use of local therapies for oligometastatic NSCLC be applied equally across all patients to avoid any health disparities.”

This work was funded by ASTRO. Dr. Iyengar reported no disclosures. Dr. Guckenberger reports relationships with the European Thoracic Oncology Platform, Varian, ViewRay, and ESTRO. Several of the coauthors disclosed relationships with industry.

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

The first guideline for definitive local therapy options in the treatment of oligometastatic non–small cell lung cancer (NSCLC) has now been released.

The result of a joint effort by the American Society for Radiation Oncology and European Society for Radiotherapy and Oncology, the guidelines emphasizes the need for a multidisciplinary team approach to guide treatment decisions for oligometastatic disease.

Historically, treatment for oligometastatic NSCLC has involved systemic therapy including chemotherapy or immunotherapy, and local therapy was given only for palliation and symptom relief. But increasing evidence has demonstrated that definitive local therapy may have an additional role in controlling tumor growth and improving survival outcomes, and an increasing number of radiation oncologists and multidisciplinary teams are now using local therapy beyond palliative care for these patients, the authors noted.

“Oligometastatic NSCLC is a phase in lung cancer development that may offer us new opportunities to improve patient outcomes, because it typically is more treatable than widely metastatic cancer,” said Puneeth Iyengar, MD, PhD, cochair of the guideline task force and an associate professor of radiation oncology at UT Southwestern Medical Center, Dallas.

“The research on local therapy for oligometastatic cancer is still at a relatively early stage, but we already see indicators of potential benefits for patients. Adding local therapy to systemic therapy may lead to more durable cancer control, potentially improving progression-free survival, overall survival and quality of life,” he said in a statement.

The new guideline is published in Practical Radiation Oncology.

The purpose of this joint guideline was to provide recommendations on local therapy use for oligometastatic NSCLC, along with a summary of the evidence justifying its incorporation into standard treatment paradigms.
 

Key recommendations

Owing to the lack of significant randomized phase 3 trials, the guideline task force strongly recommended a patient-centered, multidisciplinary approach for all decision-making regarding potential treatment. In addition, algorithms were also created for the optimal clinical scenarios for local therapy and the different types of local therapy that are available for these patients.

Key recommendations include:

• The integration of definitive local therapy is recommended only for patients who have five or fewer distant extracranial metastases, and only when technically feasible and clinically safe for all disease sites. Definitive local therapy is also conditionally recommended for carefully selected patients with synchronous oligometastatic, metachronous oligorecurrent, induced oligopersistent, or induced oligoprogressive conditions for extracranial NSCLC.
• Radiation and surgery are the only recommended modalities for definitive local treatment of oligometastatic NSCLC. Radiation is favored when multiple organ systems are being treated or when the clinical priority is to minimize breaks from systemic therapy, whereas surgery is favored when large tissue sampling is needed for molecular testing to guide systemic therapy.
• For sequencing and timing, there is an emphasis on upfront, definitive local treatment for symptomatic metastases. For asymptomatic patients with synchronous disease, at least 3 months of standard-of-care systemic therapy is recommended before starting definitive local therapy.
• For optimal staging, radiation dosing, treatment planning, and delivery techniques, there is a preference for hypofractionated radiation therapy or stereotactic body radiation therapy when appropriate. The task force also emphasizes the importance of appropriate imaging and comments that it “cannot be overstated” to diagnose oligometastatic disease; they recommend that care teams consult guidelines from groups such as the National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer.
• Patients who develop disease progression at a limited number of sites, so-called oligoprogression at previously treated sites, and/or de novo recurrences at new sites may benefit from repeat local definitive therapy performed with the aim of prolonging progression-free survival or delaying a switch in systemic therapies.

Matthias Guckenberger, MD, cochair of the guideline task force and a professor and chairman of radiation oncology at the University Hospital Zürich, cautioned that “despite the widespread enthusiasm in the field of oligometastatic disease, the quality of evidence supporting the integration of definitive local therapy into a multimodality treatment strategy is still lower as compared to indications such as locally advanced NSCLC.”

“To compensate for this lack of highest-quality evidence, recommendations of this guideline were established by a broad consensus involving experts from ASTRO and ESTRO, colleagues from the fields of thoracic surgery and medical oncology and a patient representative,” Dr. Guckenberger said in a statement.

The guideline task force also emphasized the need for equitable use of these techniques, noting that “a significant effort must be taken to ensure that the decisions regarding the use of local therapies for oligometastatic NSCLC be applied equally across all patients to avoid any health disparities.”

This work was funded by ASTRO. Dr. Iyengar reported no disclosures. Dr. Guckenberger reports relationships with the European Thoracic Oncology Platform, Varian, ViewRay, and ESTRO. Several of the coauthors disclosed relationships with industry.

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

The first guideline for definitive local therapy options in the treatment of oligometastatic non–small cell lung cancer (NSCLC) has now been released.

The result of a joint effort by the American Society for Radiation Oncology and European Society for Radiotherapy and Oncology, the guidelines emphasizes the need for a multidisciplinary team approach to guide treatment decisions for oligometastatic disease.

Historically, treatment for oligometastatic NSCLC has involved systemic therapy including chemotherapy or immunotherapy, and local therapy was given only for palliation and symptom relief. But increasing evidence has demonstrated that definitive local therapy may have an additional role in controlling tumor growth and improving survival outcomes, and an increasing number of radiation oncologists and multidisciplinary teams are now using local therapy beyond palliative care for these patients, the authors noted.

“Oligometastatic NSCLC is a phase in lung cancer development that may offer us new opportunities to improve patient outcomes, because it typically is more treatable than widely metastatic cancer,” said Puneeth Iyengar, MD, PhD, cochair of the guideline task force and an associate professor of radiation oncology at UT Southwestern Medical Center, Dallas.

“The research on local therapy for oligometastatic cancer is still at a relatively early stage, but we already see indicators of potential benefits for patients. Adding local therapy to systemic therapy may lead to more durable cancer control, potentially improving progression-free survival, overall survival and quality of life,” he said in a statement.

The new guideline is published in Practical Radiation Oncology.

The purpose of this joint guideline was to provide recommendations on local therapy use for oligometastatic NSCLC, along with a summary of the evidence justifying its incorporation into standard treatment paradigms.
 

Key recommendations

Owing to the lack of significant randomized phase 3 trials, the guideline task force strongly recommended a patient-centered, multidisciplinary approach for all decision-making regarding potential treatment. In addition, algorithms were also created for the optimal clinical scenarios for local therapy and the different types of local therapy that are available for these patients.

Key recommendations include:

• The integration of definitive local therapy is recommended only for patients who have five or fewer distant extracranial metastases, and only when technically feasible and clinically safe for all disease sites. Definitive local therapy is also conditionally recommended for carefully selected patients with synchronous oligometastatic, metachronous oligorecurrent, induced oligopersistent, or induced oligoprogressive conditions for extracranial NSCLC.
• Radiation and surgery are the only recommended modalities for definitive local treatment of oligometastatic NSCLC. Radiation is favored when multiple organ systems are being treated or when the clinical priority is to minimize breaks from systemic therapy, whereas surgery is favored when large tissue sampling is needed for molecular testing to guide systemic therapy.
• For sequencing and timing, there is an emphasis on upfront, definitive local treatment for symptomatic metastases. For asymptomatic patients with synchronous disease, at least 3 months of standard-of-care systemic therapy is recommended before starting definitive local therapy.
• For optimal staging, radiation dosing, treatment planning, and delivery techniques, there is a preference for hypofractionated radiation therapy or stereotactic body radiation therapy when appropriate. The task force also emphasizes the importance of appropriate imaging and comments that it “cannot be overstated” to diagnose oligometastatic disease; they recommend that care teams consult guidelines from groups such as the National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer.
• Patients who develop disease progression at a limited number of sites, so-called oligoprogression at previously treated sites, and/or de novo recurrences at new sites may benefit from repeat local definitive therapy performed with the aim of prolonging progression-free survival or delaying a switch in systemic therapies.

Matthias Guckenberger, MD, cochair of the guideline task force and a professor and chairman of radiation oncology at the University Hospital Zürich, cautioned that “despite the widespread enthusiasm in the field of oligometastatic disease, the quality of evidence supporting the integration of definitive local therapy into a multimodality treatment strategy is still lower as compared to indications such as locally advanced NSCLC.”

“To compensate for this lack of highest-quality evidence, recommendations of this guideline were established by a broad consensus involving experts from ASTRO and ESTRO, colleagues from the fields of thoracic surgery and medical oncology and a patient representative,” Dr. Guckenberger said in a statement.

The guideline task force also emphasized the need for equitable use of these techniques, noting that “a significant effort must be taken to ensure that the decisions regarding the use of local therapies for oligometastatic NSCLC be applied equally across all patients to avoid any health disparities.”

This work was funded by ASTRO. Dr. Iyengar reported no disclosures. Dr. Guckenberger reports relationships with the European Thoracic Oncology Platform, Varian, ViewRay, and ESTRO. Several of the coauthors disclosed relationships with industry.

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

Cisplatin is one of the most commonly used chemotherapeutic agents for treating a variety of cancers, such as lung, bladder, and ovarian cancers. But the therapy comes with a drawback – ototoxicity.

“More than half of adult and pediatric patients with cancer treated with cisplatin developed hearing impairment with major impact on patients’ health-related quality of life,” researchers noted in a clinical review published in JCO Oncology Practice.

It is estimated that 36% of adult patients and 40%-60% of pediatric patients experience cisplatin-induced ototoxicity. It can present as tinnitus (ringing in the ears), loss of hearing in the high-frequency range (4000 – 8000 Hz), or, at late stages, a decrease in the ability to hear lower frequencies.

The incidence of cisplatin-induced ototoxicity is estimated to be 36% of adult patients and 40% to 60% of pediatric patients. Ototoxicity can present as tinnitus, loss of hearing in the high-frequency range (4,000-8,000 Hz), or, at late stages, a decrease in the ability to hear lower frequencies.

The risk of developing cisplatin-induced ototoxicity depends on various factors, including the cumulative dose of cisplatin, the duration of treatment, and individual patient factors, such as age and preexisting hearing problems.

The lack of real-world practice patterns for monitoring ototoxicity makes identifying effective prevention and intervention strategies challenging, say the authors, led by Asmi Chattaraj, MD, of the University of Pittsburgh Medical Center (UPMC), McKeesport, Pa.

The team conducted a survey of oncologists with the UPMC Hillman Cancer Center network regarding patterns for monitoring and reducing the risk of ototoxicity.

Of the 35 responding oncologists, the majority (97%) indicated that they regularly discuss the risk of ototoxicity with all patients before they receive cisplatin. However, only 18% of the respondents said they obtain audiograms for patients before administering cisplatin, 69% order audiograms only if patients complain of hearing loss or tinnitus, and 35% of respondents do not perform regular monitoring for ototoxicity.

“This heterogeneity of practice within a single network highlights the need for high-quality evidence to guide clinical practice and the urgent need to standardize the necessary diagnostic steps to monitor for ototoxicity and its effect on the quality of life in the adult oncology practice, similar to the current practice in the pediatric patient population,” the researchers determined.
 

Proactive rather than reactive

Managing cisplatin-induced ototoxicity “must be viewed as a proactive measure rather than a reactive measure,” Nisha A. Mohindra, MD, wrote in an accompanying editorial.

Dr. Mohindra noted that although it is recommended that audiology assessments be conducted before, during, and after administration of ototoxicity drugs, the monitoring for ototoxicity remains underutilized in clinical practice. The path to better outcomes begins with implementing testing into clinical practice, she suggested.

“The most effective mechanism to manage ototoxicity currently is to identify patients at risk and implement programs to support ongoing monitoring,” Dr. Mohindra wrote.

“Even if ototoxicity cannot be prevented in some patients, providing treating oncologists with a timely opportunity to alter therapy or providing patients with support, guidance, and earlier access to rehabilitation services may mitigate long-term effects of hearing loss,” she concluded.

The researchers have disclosed numerous relationships with industry, a full listing of which is available with the original article.

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

Cisplatin is one of the most commonly used chemotherapeutic agents for treating a variety of cancers, such as lung, bladder, and ovarian cancers. But the therapy comes with a drawback – ototoxicity.

“More than half of adult and pediatric patients with cancer treated with cisplatin developed hearing impairment with major impact on patients’ health-related quality of life,” researchers noted in a clinical review published in JCO Oncology Practice.

It is estimated that 36% of adult patients and 40%-60% of pediatric patients experience cisplatin-induced ototoxicity. It can present as tinnitus (ringing in the ears), loss of hearing in the high-frequency range (4000 – 8000 Hz), or, at late stages, a decrease in the ability to hear lower frequencies.

The incidence of cisplatin-induced ototoxicity is estimated to be 36% of adult patients and 40% to 60% of pediatric patients. Ototoxicity can present as tinnitus, loss of hearing in the high-frequency range (4,000-8,000 Hz), or, at late stages, a decrease in the ability to hear lower frequencies.

The risk of developing cisplatin-induced ototoxicity depends on various factors, including the cumulative dose of cisplatin, the duration of treatment, and individual patient factors, such as age and preexisting hearing problems.

The lack of real-world practice patterns for monitoring ototoxicity makes identifying effective prevention and intervention strategies challenging, say the authors, led by Asmi Chattaraj, MD, of the University of Pittsburgh Medical Center (UPMC), McKeesport, Pa.

The team conducted a survey of oncologists with the UPMC Hillman Cancer Center network regarding patterns for monitoring and reducing the risk of ototoxicity.

Of the 35 responding oncologists, the majority (97%) indicated that they regularly discuss the risk of ototoxicity with all patients before they receive cisplatin. However, only 18% of the respondents said they obtain audiograms for patients before administering cisplatin, 69% order audiograms only if patients complain of hearing loss or tinnitus, and 35% of respondents do not perform regular monitoring for ototoxicity.

“This heterogeneity of practice within a single network highlights the need for high-quality evidence to guide clinical practice and the urgent need to standardize the necessary diagnostic steps to monitor for ototoxicity and its effect on the quality of life in the adult oncology practice, similar to the current practice in the pediatric patient population,” the researchers determined.
 

Proactive rather than reactive

Managing cisplatin-induced ototoxicity “must be viewed as a proactive measure rather than a reactive measure,” Nisha A. Mohindra, MD, wrote in an accompanying editorial.

Dr. Mohindra noted that although it is recommended that audiology assessments be conducted before, during, and after administration of ototoxicity drugs, the monitoring for ototoxicity remains underutilized in clinical practice. The path to better outcomes begins with implementing testing into clinical practice, she suggested.

“The most effective mechanism to manage ototoxicity currently is to identify patients at risk and implement programs to support ongoing monitoring,” Dr. Mohindra wrote.

“Even if ototoxicity cannot be prevented in some patients, providing treating oncologists with a timely opportunity to alter therapy or providing patients with support, guidance, and earlier access to rehabilitation services may mitigate long-term effects of hearing loss,” she concluded.

The researchers have disclosed numerous relationships with industry, a full listing of which is available with the original article.

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

Cisplatin is one of the most commonly used chemotherapeutic agents for treating a variety of cancers, such as lung, bladder, and ovarian cancers. But the therapy comes with a drawback – ototoxicity.

“More than half of adult and pediatric patients with cancer treated with cisplatin developed hearing impairment with major impact on patients’ health-related quality of life,” researchers noted in a clinical review published in JCO Oncology Practice.

It is estimated that 36% of adult patients and 40%-60% of pediatric patients experience cisplatin-induced ototoxicity. It can present as tinnitus (ringing in the ears), loss of hearing in the high-frequency range (4000 – 8000 Hz), or, at late stages, a decrease in the ability to hear lower frequencies.

The incidence of cisplatin-induced ototoxicity is estimated to be 36% of adult patients and 40% to 60% of pediatric patients. Ototoxicity can present as tinnitus, loss of hearing in the high-frequency range (4,000-8,000 Hz), or, at late stages, a decrease in the ability to hear lower frequencies.

The risk of developing cisplatin-induced ototoxicity depends on various factors, including the cumulative dose of cisplatin, the duration of treatment, and individual patient factors, such as age and preexisting hearing problems.

The lack of real-world practice patterns for monitoring ototoxicity makes identifying effective prevention and intervention strategies challenging, say the authors, led by Asmi Chattaraj, MD, of the University of Pittsburgh Medical Center (UPMC), McKeesport, Pa.

The team conducted a survey of oncologists with the UPMC Hillman Cancer Center network regarding patterns for monitoring and reducing the risk of ototoxicity.

Of the 35 responding oncologists, the majority (97%) indicated that they regularly discuss the risk of ototoxicity with all patients before they receive cisplatin. However, only 18% of the respondents said they obtain audiograms for patients before administering cisplatin, 69% order audiograms only if patients complain of hearing loss or tinnitus, and 35% of respondents do not perform regular monitoring for ototoxicity.

“This heterogeneity of practice within a single network highlights the need for high-quality evidence to guide clinical practice and the urgent need to standardize the necessary diagnostic steps to monitor for ototoxicity and its effect on the quality of life in the adult oncology practice, similar to the current practice in the pediatric patient population,” the researchers determined.
 

Proactive rather than reactive

Managing cisplatin-induced ototoxicity “must be viewed as a proactive measure rather than a reactive measure,” Nisha A. Mohindra, MD, wrote in an accompanying editorial.

Dr. Mohindra noted that although it is recommended that audiology assessments be conducted before, during, and after administration of ototoxicity drugs, the monitoring for ototoxicity remains underutilized in clinical practice. The path to better outcomes begins with implementing testing into clinical practice, she suggested.

“The most effective mechanism to manage ototoxicity currently is to identify patients at risk and implement programs to support ongoing monitoring,” Dr. Mohindra wrote.

“Even if ototoxicity cannot be prevented in some patients, providing treating oncologists with a timely opportunity to alter therapy or providing patients with support, guidance, and earlier access to rehabilitation services may mitigate long-term effects of hearing loss,” she concluded.

The researchers have disclosed numerous relationships with industry, a full listing of which is available with the original article.

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

A new study shows that people with long COVID respond differently to COVID vaccines and that the condition may be caused by a dysfunction of the immune system – possibly explaining why some people experience symptoms for months while others recover and resume normal lives. 

The study compared people who already had long COVID with people who had recovered from the virus. Both groups had not yet been vaccinated prior to the study. When researchers analyzed blood samples after people received an initial vaccine dose, they found that people with long COVID and people who had already recovered from the virus had similar immune responses at first. But after 8 weeks, the long-COVID group’s immune response remained elevated, while the other group’s response had declined.

The long-COVID group also showed an extra immune response that tried to fight the virus in a secondary way that researchers didn’t expect. Both groups showed an initial increase in their blood of antibodies that primarily target what’s known as the “spike” protein of the coronavirus, which allows the virus to invade healthy cells. But the long-COVID group also showed a prolonged increased immune response that tried to fight the part of the virus related to how it replicates.

“Theoretically, the production of these antibodies could mean that people are more protected from infection,” said researcher Catherine Le, MD, in a statement. “We also need to investigate if the elevated immune response corresponds with severity or number of long–COVID-19 symptoms.”

Dr. Le is codirector of the COVID-19 Recovery Program at Cedars-Sinai Medical Center in Los Angeles, where the study was conducted.

Study participants agreed in September 2020 to participate in long-term COVID research at Cedars-Sinai. The new analysis was published earlier this year in BMC Infectious Diseases and included 245 people who had long COVID and 86 health care workers who had recovered from COVID but did not have long-term symptoms. 

For the study, long COVID was defined as having symptoms that lasted more than 12 weeks. Common long-COVID symptoms are fatigue, shortness of breath, and brain dysfunction such as confusion and forgetfulness.

The authors said it’s unclear why the two groups had different immune responses and also noted that their study was limited by a small sample size. Their research of blood samples is ongoing, with the goals of identifying a way to diagnose long COVID with a laboratory test and of better understanding what causes the condition.

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

A new study shows that people with long COVID respond differently to COVID vaccines and that the condition may be caused by a dysfunction of the immune system – possibly explaining why some people experience symptoms for months while others recover and resume normal lives. 

The study compared people who already had long COVID with people who had recovered from the virus. Both groups had not yet been vaccinated prior to the study. When researchers analyzed blood samples after people received an initial vaccine dose, they found that people with long COVID and people who had already recovered from the virus had similar immune responses at first. But after 8 weeks, the long-COVID group’s immune response remained elevated, while the other group’s response had declined.

The long-COVID group also showed an extra immune response that tried to fight the virus in a secondary way that researchers didn’t expect. Both groups showed an initial increase in their blood of antibodies that primarily target what’s known as the “spike” protein of the coronavirus, which allows the virus to invade healthy cells. But the long-COVID group also showed a prolonged increased immune response that tried to fight the part of the virus related to how it replicates.

“Theoretically, the production of these antibodies could mean that people are more protected from infection,” said researcher Catherine Le, MD, in a statement. “We also need to investigate if the elevated immune response corresponds with severity or number of long–COVID-19 symptoms.”

Dr. Le is codirector of the COVID-19 Recovery Program at Cedars-Sinai Medical Center in Los Angeles, where the study was conducted.

Study participants agreed in September 2020 to participate in long-term COVID research at Cedars-Sinai. The new analysis was published earlier this year in BMC Infectious Diseases and included 245 people who had long COVID and 86 health care workers who had recovered from COVID but did not have long-term symptoms. 

For the study, long COVID was defined as having symptoms that lasted more than 12 weeks. Common long-COVID symptoms are fatigue, shortness of breath, and brain dysfunction such as confusion and forgetfulness.

The authors said it’s unclear why the two groups had different immune responses and also noted that their study was limited by a small sample size. Their research of blood samples is ongoing, with the goals of identifying a way to diagnose long COVID with a laboratory test and of better understanding what causes the condition.

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

A new study shows that people with long COVID respond differently to COVID vaccines and that the condition may be caused by a dysfunction of the immune system – possibly explaining why some people experience symptoms for months while others recover and resume normal lives. 

The study compared people who already had long COVID with people who had recovered from the virus. Both groups had not yet been vaccinated prior to the study. When researchers analyzed blood samples after people received an initial vaccine dose, they found that people with long COVID and people who had already recovered from the virus had similar immune responses at first. But after 8 weeks, the long-COVID group’s immune response remained elevated, while the other group’s response had declined.

The long-COVID group also showed an extra immune response that tried to fight the virus in a secondary way that researchers didn’t expect. Both groups showed an initial increase in their blood of antibodies that primarily target what’s known as the “spike” protein of the coronavirus, which allows the virus to invade healthy cells. But the long-COVID group also showed a prolonged increased immune response that tried to fight the part of the virus related to how it replicates.

“Theoretically, the production of these antibodies could mean that people are more protected from infection,” said researcher Catherine Le, MD, in a statement. “We also need to investigate if the elevated immune response corresponds with severity or number of long–COVID-19 symptoms.”

Dr. Le is codirector of the COVID-19 Recovery Program at Cedars-Sinai Medical Center in Los Angeles, where the study was conducted.

Study participants agreed in September 2020 to participate in long-term COVID research at Cedars-Sinai. The new analysis was published earlier this year in BMC Infectious Diseases and included 245 people who had long COVID and 86 health care workers who had recovered from COVID but did not have long-term symptoms. 

For the study, long COVID was defined as having symptoms that lasted more than 12 weeks. Common long-COVID symptoms are fatigue, shortness of breath, and brain dysfunction such as confusion and forgetfulness.

The authors said it’s unclear why the two groups had different immune responses and also noted that their study was limited by a small sample size. Their research of blood samples is ongoing, with the goals of identifying a way to diagnose long COVID with a laboratory test and of better understanding what causes the condition.

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

A few weeks ago I asked what changes would have to occur to return urgent care to its former place under the umbrella of the primary care pediatrician. Several responses that I received and the recent story about screenings in this magazine (April 2023) have prompted me to ask the broader question of what is a pediatrician? More specifically, what is the role of a primary care pediatrician?

I think we can agree that a pediatrician is someone who has dedicated his or her training to learning about and then treating the diseases of children. There are pediatricians whose focus is on newborns. There are others who specialize by organ system or by the intensity of the disease (for example, hospitalists and ED physicians). In Great Britain, and to some extent Canada, “paediatricians” serve primarily as consultants to other health care providers. In this country, however, we tend to think of a pediatrician as a frontline primary care physician with general expertise in children. It is those providers (myself included) to whom I address my questions: “What is our role? What is our primary mission?” Are the expectations that we and others have for us realistic given the realities of 21st-century America? And, is our failure to meet some of those expectations contributing to our burnout?

Are we preventionists? I have always thought that one of the things that sets us apart from other specialties is our focus on prevention. We’ve done a pretty good job with infectious diseases thanks to vaccines and antibiotics. But, when I look at the children who grew to be obese adults under my care I have to say that I and my peers have done an abysmal job of prevention. And that is just one example.

Are we educators responsible for helping parents learn what we consider to be the best child-rearing practices? The Latin root of the word “doctor” means teacher. But, education done well is a very time-consuming process. How many of us have time in the office to really teach? Furthermore, some recent studies on managing vaccine deniers suggests that education doesn’t work with people who have long-held beliefs.

Are we data-entry clerks tasked with documenting our every professional step to validate our value to society and the correctness of our methods? It seems that there are some folks who believe we should be.

Are we screeners? TSA agents with white coats and stethoscopes responsible for screening the entire population for potential threats that weren’t obvious to our thoughtful history taking and careful physical examinations?

And finally, are we healers? If you haven’t already disabused yourself of that myth please take a moment to consider the number of cures you have orchestrated in the last 10 years.

The answer is that we can and maybe should be all of those things but we and those who advise us and support us must have reasonable expectations of how difficult it can be to be all those things to all of our patients in the real world of primary care pediatrics. We aren’t social engineers who can level every inequality nor can we orchestrate changes in a society that leans toward enabling unhealthy lifestyles.

The American Academy of Pediatrics must shoulder some of the blame for this discrepancy between expectations and reality. In the Pediatric News article on screening, Susan Kressly, MD, the chair of the American Academy of Pediatrics’s Section on Administration and Practice shares some common-sense observations on how screening can be applied thoughtfully. However, this isn’t how it is usually portrayed in the top-down rollout as each advocacy group releases its next best screening recommendations.

Faced with this clash or expectations I have always chosen to think small. I live in a small town in a small state. I look at each patient and each family, one at a time, with its strengths and its vulnerabilities as a given. I try to educate and prevent as their needs and my time allows. I screen when something makes me feel uncomfortable. Long ago I retired my aspirations as a healer and instead have focussed on being a soother.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

A few weeks ago I asked what changes would have to occur to return urgent care to its former place under the umbrella of the primary care pediatrician. Several responses that I received and the recent story about screenings in this magazine (April 2023) have prompted me to ask the broader question of what is a pediatrician? More specifically, what is the role of a primary care pediatrician?

I think we can agree that a pediatrician is someone who has dedicated his or her training to learning about and then treating the diseases of children. There are pediatricians whose focus is on newborns. There are others who specialize by organ system or by the intensity of the disease (for example, hospitalists and ED physicians). In Great Britain, and to some extent Canada, “paediatricians” serve primarily as consultants to other health care providers. In this country, however, we tend to think of a pediatrician as a frontline primary care physician with general expertise in children. It is those providers (myself included) to whom I address my questions: “What is our role? What is our primary mission?” Are the expectations that we and others have for us realistic given the realities of 21st-century America? And, is our failure to meet some of those expectations contributing to our burnout?

Are we preventionists? I have always thought that one of the things that sets us apart from other specialties is our focus on prevention. We’ve done a pretty good job with infectious diseases thanks to vaccines and antibiotics. But, when I look at the children who grew to be obese adults under my care I have to say that I and my peers have done an abysmal job of prevention. And that is just one example.

Are we educators responsible for helping parents learn what we consider to be the best child-rearing practices? The Latin root of the word “doctor” means teacher. But, education done well is a very time-consuming process. How many of us have time in the office to really teach? Furthermore, some recent studies on managing vaccine deniers suggests that education doesn’t work with people who have long-held beliefs.

Are we data-entry clerks tasked with documenting our every professional step to validate our value to society and the correctness of our methods? It seems that there are some folks who believe we should be.

Are we screeners? TSA agents with white coats and stethoscopes responsible for screening the entire population for potential threats that weren’t obvious to our thoughtful history taking and careful physical examinations?

And finally, are we healers? If you haven’t already disabused yourself of that myth please take a moment to consider the number of cures you have orchestrated in the last 10 years.

The answer is that we can and maybe should be all of those things but we and those who advise us and support us must have reasonable expectations of how difficult it can be to be all those things to all of our patients in the real world of primary care pediatrics. We aren’t social engineers who can level every inequality nor can we orchestrate changes in a society that leans toward enabling unhealthy lifestyles.

The American Academy of Pediatrics must shoulder some of the blame for this discrepancy between expectations and reality. In the Pediatric News article on screening, Susan Kressly, MD, the chair of the American Academy of Pediatrics’s Section on Administration and Practice shares some common-sense observations on how screening can be applied thoughtfully. However, this isn’t how it is usually portrayed in the top-down rollout as each advocacy group releases its next best screening recommendations.

Faced with this clash or expectations I have always chosen to think small. I live in a small town in a small state. I look at each patient and each family, one at a time, with its strengths and its vulnerabilities as a given. I try to educate and prevent as their needs and my time allows. I screen when something makes me feel uncomfortable. Long ago I retired my aspirations as a healer and instead have focussed on being a soother.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

A few weeks ago I asked what changes would have to occur to return urgent care to its former place under the umbrella of the primary care pediatrician. Several responses that I received and the recent story about screenings in this magazine (April 2023) have prompted me to ask the broader question of what is a pediatrician? More specifically, what is the role of a primary care pediatrician?

I think we can agree that a pediatrician is someone who has dedicated his or her training to learning about and then treating the diseases of children. There are pediatricians whose focus is on newborns. There are others who specialize by organ system or by the intensity of the disease (for example, hospitalists and ED physicians). In Great Britain, and to some extent Canada, “paediatricians” serve primarily as consultants to other health care providers. In this country, however, we tend to think of a pediatrician as a frontline primary care physician with general expertise in children. It is those providers (myself included) to whom I address my questions: “What is our role? What is our primary mission?” Are the expectations that we and others have for us realistic given the realities of 21st-century America? And, is our failure to meet some of those expectations contributing to our burnout?

Are we preventionists? I have always thought that one of the things that sets us apart from other specialties is our focus on prevention. We’ve done a pretty good job with infectious diseases thanks to vaccines and antibiotics. But, when I look at the children who grew to be obese adults under my care I have to say that I and my peers have done an abysmal job of prevention. And that is just one example.

Are we educators responsible for helping parents learn what we consider to be the best child-rearing practices? The Latin root of the word “doctor” means teacher. But, education done well is a very time-consuming process. How many of us have time in the office to really teach? Furthermore, some recent studies on managing vaccine deniers suggests that education doesn’t work with people who have long-held beliefs.

Are we data-entry clerks tasked with documenting our every professional step to validate our value to society and the correctness of our methods? It seems that there are some folks who believe we should be.

Are we screeners? TSA agents with white coats and stethoscopes responsible for screening the entire population for potential threats that weren’t obvious to our thoughtful history taking and careful physical examinations?

And finally, are we healers? If you haven’t already disabused yourself of that myth please take a moment to consider the number of cures you have orchestrated in the last 10 years.

The answer is that we can and maybe should be all of those things but we and those who advise us and support us must have reasonable expectations of how difficult it can be to be all those things to all of our patients in the real world of primary care pediatrics. We aren’t social engineers who can level every inequality nor can we orchestrate changes in a society that leans toward enabling unhealthy lifestyles.

The American Academy of Pediatrics must shoulder some of the blame for this discrepancy between expectations and reality. In the Pediatric News article on screening, Susan Kressly, MD, the chair of the American Academy of Pediatrics’s Section on Administration and Practice shares some common-sense observations on how screening can be applied thoughtfully. However, this isn’t how it is usually portrayed in the top-down rollout as each advocacy group releases its next best screening recommendations.

Faced with this clash or expectations I have always chosen to think small. I live in a small town in a small state. I look at each patient and each family, one at a time, with its strengths and its vulnerabilities as a given. I try to educate and prevent as their needs and my time allows. I screen when something makes me feel uncomfortable. Long ago I retired my aspirations as a healer and instead have focussed on being a soother.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

BOSTON – In patients with primary progressive multiple sclerosis (PPMS), machine learning can predict progression with reasonable accuracy on the basis of the blood transcriptome, according to a proof-of-concept study presented at the 2023 annual meeting of the American Academy of Neurology.

The accuracy was sufficient for the lead author of the study, Michael Gurevich, PhD, head of the Neuroimmunological Laboratory in the Multiple Sclerosis Center of Sheba Medical Center in Ramat Gan, Israel, to say that it is already clinically viable even as the tool is still evolving.

“We are looking at larger sample sizes to improve the accuracy and generalizability of our model, but we can use it now to inform treatment decisions,” Dr. Gurevich said.

In patients with PPMS who have a highly variable course, the model predicts disability progression with an accuracy of approximately 70%, according to the data he presented. He said he believes this is already at a level that it is meaningful for a risk-to-benefit calculation when considering treatment.
 

Machine learning analyzes blood samples

The study pursues the concept that the genetic information governing highly complex pathophysiological processes is contained in RNA sequencing. While multimodal omics generate data that are too complex for human pattern recognition, there is a growing body of evidence, including that provided by this study, to suggest that machine learning can employ these same RNA profiles and predict disease activity.

In this study, blood samples were collected from patients who participated in the phase 3 clinical ORATORIO trial that led to approval of ocrelizumab for PPMS. Analyses were conducted only on blood samples from those randomized to placebo, who, like those in the active treatment arm, were evaluated at baseline and at 12-week intervals for more than 2 years.

After development of a prediction model and creation of a training dataset, machine learning was applied to the deep sequencing of the blood transcriptome data for predicting two endpoints. One was disease progression at 120 weeks defined as a 1 point or more increase in the Expanded Disability Status Scale (EDSS) among patients with confirmed disability progression for at least 12 weeks (12W-CDP).

The other was change at 120 weeks in brain morphology defined as a 1% or more reduction in brain volume (120W PBVC).

The peripheral blood samples were subjected to RNA sequencing analysis (RNA-Seq) using commercially available analysis techniques. The prediction model for the disability endpoint was based on data generated from the blood transcriptome of 135 patients of which 53 (39%) met the endpoint at 120 weeks. The prediction model for the change in brain morphology was based on the blood transcriptome from 94 patients of which 63 (67%) met the endpoint.

On the basis of 10 genes that most significantly differentiated those who met the disability endpoint from those who did not, machine recognition of patterns after training was able to predict correctly the outcome in 70.9%. The sensitivity was 55.6%, and the specificity was 79.0%. The positive and negative predictive values were 59.0% and 76.8%, respectively.

On the basis of the 12 genes the most significantly differentiated those that reached the 120W PBVC endpoint from those who did not, machine learning resulted in a correct prediction of outcomes in 75.1%. The sensitivity was 78.1%, and the specificity was 66.7%. The positive and negative predictive values were 83.3% and 58.8%, respectively

Typical of a PPMS trial population, the mean age of the patients was about 44 years. The mean disease duration was about 6 years. The majority of patients had an EDSS score below 5.5 at baseline. The baseline T2 lesion number was approximately 50.

If further validated by others and in larger studies, this type of information could play a valuable role in PPMS management, according to Dr. Gurevich. Now that there is an approved therapy for PPMS, it can help clinicians and patients determine whether to initiate treatment early to address the high risk of progression or delay treatment that might not be needed.
 

A useful tool

In the field of MS, most of the studies performed with machine learning have focused on the analysis of radiological images. However, others are now looking at the blood transcriptome as a potential path to better classifying a highly complex disease with substantial heterogeneity in presentation, progression, and outcome.

For example, machine learning of the blood transcriptome has also shown high accuracy in the diagnosis and classification of MS in patients with clinically isolated syndrome (CIS). One study, published in Cell Reports Medicine, was led by Cinthia Farina, PhD, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, Milan.

Although she did not hear the presentation by Dr. Gurevich, Dr. Farina is enthusiastic about the potential for machine learning to help manage MS through the analysis of the blood transcriptome. “I do believe that transcriptomics in peripheral immune cells may become a useful tool for MS diagnosis and prognosis,” she said.

In her own study, in which machine learning algorithms were developed and trained on the basis of peripheral blood from patients with CIS, the tool proved accurate with a strong potential for being incorporated into routine clinical management.

“Machine learning applied to the blood transcriptomes was extremely efficient with a 95.6% accuracy in discriminating PPMS from RRMS [relapsing-remitting] MS,” she reported.

Dr. Gurevich has no potential financial conflicts of interest to report. He reported funding for the study was provided by Roche. Dr. Farina reports financial relationships with Merck-Serono, Novartis, and Teva.

BOSTON – In patients with primary progressive multiple sclerosis (PPMS), machine learning can predict progression with reasonable accuracy on the basis of the blood transcriptome, according to a proof-of-concept study presented at the 2023 annual meeting of the American Academy of Neurology.

The accuracy was sufficient for the lead author of the study, Michael Gurevich, PhD, head of the Neuroimmunological Laboratory in the Multiple Sclerosis Center of Sheba Medical Center in Ramat Gan, Israel, to say that it is already clinically viable even as the tool is still evolving.

“We are looking at larger sample sizes to improve the accuracy and generalizability of our model, but we can use it now to inform treatment decisions,” Dr. Gurevich said.

In patients with PPMS who have a highly variable course, the model predicts disability progression with an accuracy of approximately 70%, according to the data he presented. He said he believes this is already at a level that it is meaningful for a risk-to-benefit calculation when considering treatment.
 

Machine learning analyzes blood samples

The study pursues the concept that the genetic information governing highly complex pathophysiological processes is contained in RNA sequencing. While multimodal omics generate data that are too complex for human pattern recognition, there is a growing body of evidence, including that provided by this study, to suggest that machine learning can employ these same RNA profiles and predict disease activity.

In this study, blood samples were collected from patients who participated in the phase 3 clinical ORATORIO trial that led to approval of ocrelizumab for PPMS. Analyses were conducted only on blood samples from those randomized to placebo, who, like those in the active treatment arm, were evaluated at baseline and at 12-week intervals for more than 2 years.

After development of a prediction model and creation of a training dataset, machine learning was applied to the deep sequencing of the blood transcriptome data for predicting two endpoints. One was disease progression at 120 weeks defined as a 1 point or more increase in the Expanded Disability Status Scale (EDSS) among patients with confirmed disability progression for at least 12 weeks (12W-CDP).

The other was change at 120 weeks in brain morphology defined as a 1% or more reduction in brain volume (120W PBVC).

The peripheral blood samples were subjected to RNA sequencing analysis (RNA-Seq) using commercially available analysis techniques. The prediction model for the disability endpoint was based on data generated from the blood transcriptome of 135 patients of which 53 (39%) met the endpoint at 120 weeks. The prediction model for the change in brain morphology was based on the blood transcriptome from 94 patients of which 63 (67%) met the endpoint.

On the basis of 10 genes that most significantly differentiated those who met the disability endpoint from those who did not, machine recognition of patterns after training was able to predict correctly the outcome in 70.9%. The sensitivity was 55.6%, and the specificity was 79.0%. The positive and negative predictive values were 59.0% and 76.8%, respectively.

On the basis of the 12 genes the most significantly differentiated those that reached the 120W PBVC endpoint from those who did not, machine learning resulted in a correct prediction of outcomes in 75.1%. The sensitivity was 78.1%, and the specificity was 66.7%. The positive and negative predictive values were 83.3% and 58.8%, respectively

Typical of a PPMS trial population, the mean age of the patients was about 44 years. The mean disease duration was about 6 years. The majority of patients had an EDSS score below 5.5 at baseline. The baseline T2 lesion number was approximately 50.

If further validated by others and in larger studies, this type of information could play a valuable role in PPMS management, according to Dr. Gurevich. Now that there is an approved therapy for PPMS, it can help clinicians and patients determine whether to initiate treatment early to address the high risk of progression or delay treatment that might not be needed.
 

A useful tool

In the field of MS, most of the studies performed with machine learning have focused on the analysis of radiological images. However, others are now looking at the blood transcriptome as a potential path to better classifying a highly complex disease with substantial heterogeneity in presentation, progression, and outcome.

For example, machine learning of the blood transcriptome has also shown high accuracy in the diagnosis and classification of MS in patients with clinically isolated syndrome (CIS). One study, published in Cell Reports Medicine, was led by Cinthia Farina, PhD, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, Milan.

Although she did not hear the presentation by Dr. Gurevich, Dr. Farina is enthusiastic about the potential for machine learning to help manage MS through the analysis of the blood transcriptome. “I do believe that transcriptomics in peripheral immune cells may become a useful tool for MS diagnosis and prognosis,” she said.

In her own study, in which machine learning algorithms were developed and trained on the basis of peripheral blood from patients with CIS, the tool proved accurate with a strong potential for being incorporated into routine clinical management.

“Machine learning applied to the blood transcriptomes was extremely efficient with a 95.6% accuracy in discriminating PPMS from RRMS [relapsing-remitting] MS,” she reported.

Dr. Gurevich has no potential financial conflicts of interest to report. He reported funding for the study was provided by Roche. Dr. Farina reports financial relationships with Merck-Serono, Novartis, and Teva.

BOSTON – In patients with primary progressive multiple sclerosis (PPMS), machine learning can predict progression with reasonable accuracy on the basis of the blood transcriptome, according to a proof-of-concept study presented at the 2023 annual meeting of the American Academy of Neurology.

The accuracy was sufficient for the lead author of the study, Michael Gurevich, PhD, head of the Neuroimmunological Laboratory in the Multiple Sclerosis Center of Sheba Medical Center in Ramat Gan, Israel, to say that it is already clinically viable even as the tool is still evolving.

“We are looking at larger sample sizes to improve the accuracy and generalizability of our model, but we can use it now to inform treatment decisions,” Dr. Gurevich said.

In patients with PPMS who have a highly variable course, the model predicts disability progression with an accuracy of approximately 70%, according to the data he presented. He said he believes this is already at a level that it is meaningful for a risk-to-benefit calculation when considering treatment.
 

Machine learning analyzes blood samples

The study pursues the concept that the genetic information governing highly complex pathophysiological processes is contained in RNA sequencing. While multimodal omics generate data that are too complex for human pattern recognition, there is a growing body of evidence, including that provided by this study, to suggest that machine learning can employ these same RNA profiles and predict disease activity.

In this study, blood samples were collected from patients who participated in the phase 3 clinical ORATORIO trial that led to approval of ocrelizumab for PPMS. Analyses were conducted only on blood samples from those randomized to placebo, who, like those in the active treatment arm, were evaluated at baseline and at 12-week intervals for more than 2 years.

After development of a prediction model and creation of a training dataset, machine learning was applied to the deep sequencing of the blood transcriptome data for predicting two endpoints. One was disease progression at 120 weeks defined as a 1 point or more increase in the Expanded Disability Status Scale (EDSS) among patients with confirmed disability progression for at least 12 weeks (12W-CDP).

The other was change at 120 weeks in brain morphology defined as a 1% or more reduction in brain volume (120W PBVC).

The peripheral blood samples were subjected to RNA sequencing analysis (RNA-Seq) using commercially available analysis techniques. The prediction model for the disability endpoint was based on data generated from the blood transcriptome of 135 patients of which 53 (39%) met the endpoint at 120 weeks. The prediction model for the change in brain morphology was based on the blood transcriptome from 94 patients of which 63 (67%) met the endpoint.

On the basis of 10 genes that most significantly differentiated those who met the disability endpoint from those who did not, machine recognition of patterns after training was able to predict correctly the outcome in 70.9%. The sensitivity was 55.6%, and the specificity was 79.0%. The positive and negative predictive values were 59.0% and 76.8%, respectively.

On the basis of the 12 genes the most significantly differentiated those that reached the 120W PBVC endpoint from those who did not, machine learning resulted in a correct prediction of outcomes in 75.1%. The sensitivity was 78.1%, and the specificity was 66.7%. The positive and negative predictive values were 83.3% and 58.8%, respectively

Typical of a PPMS trial population, the mean age of the patients was about 44 years. The mean disease duration was about 6 years. The majority of patients had an EDSS score below 5.5 at baseline. The baseline T2 lesion number was approximately 50.

If further validated by others and in larger studies, this type of information could play a valuable role in PPMS management, according to Dr. Gurevich. Now that there is an approved therapy for PPMS, it can help clinicians and patients determine whether to initiate treatment early to address the high risk of progression or delay treatment that might not be needed.
 

A useful tool

In the field of MS, most of the studies performed with machine learning have focused on the analysis of radiological images. However, others are now looking at the blood transcriptome as a potential path to better classifying a highly complex disease with substantial heterogeneity in presentation, progression, and outcome.

For example, machine learning of the blood transcriptome has also shown high accuracy in the diagnosis and classification of MS in patients with clinically isolated syndrome (CIS). One study, published in Cell Reports Medicine, was led by Cinthia Farina, PhD, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, Milan.

Although she did not hear the presentation by Dr. Gurevich, Dr. Farina is enthusiastic about the potential for machine learning to help manage MS through the analysis of the blood transcriptome. “I do believe that transcriptomics in peripheral immune cells may become a useful tool for MS diagnosis and prognosis,” she said.

In her own study, in which machine learning algorithms were developed and trained on the basis of peripheral blood from patients with CIS, the tool proved accurate with a strong potential for being incorporated into routine clinical management.

“Machine learning applied to the blood transcriptomes was extremely efficient with a 95.6% accuracy in discriminating PPMS from RRMS [relapsing-remitting] MS,” she reported.

Dr. Gurevich has no potential financial conflicts of interest to report. He reported funding for the study was provided by Roche. Dr. Farina reports financial relationships with Merck-Serono, Novartis, and Teva.

In the United States, type 2 diabetes (T2D) more commonly affects people older than 40 years, but it is most prevalent among adults over age 65, affecting more than 29% of this population. The heterogeneity in the health and functional status of older adults presents a challenge in the management and treatment of older patients with T2D. Moreover, there is an increased risk for health-related comorbidities and complications from diabetes treatment (for example, hypoglycemia) in older adults. Physiologic changes, such as decreased renal function, cognitive decline, and sarcopenia, may lead to an increased risk for adverse reactions to medications and require an individualized treatment approach. Although there have been a limited number of randomized controlled studies targeting older adults with multiple comorbidities and poor health status, subanalyses of diabetes trials with a subpopulation of older adults have provided additional evidence to better guide therapeutic approaches in caring for older patients with T2D.

Here’s a guide to developing personalized therapeutic regimens for older patients with T2D using lifestyle interventions, pharmacotherapy, and diabetes technology.
 

Determining an optimal glycemic target

An important first step in diabetes treatment is to determine the optimal glycemic target for patients. Although data support intensive glycemic control (hemoglobin A1c < 7%) to prevent complications from diabetes in younger patients with recently diagnosed disease, the data are less compelling in trials involving older populations with longer durations of T2D. One observational study with 71,092 older adults over age 60 reported a U-shaped correlation between A1c and mortality, with higher risks for mortality in those with A1c levels < 6% and ≥ 11%, compared with those with A1c levels of 6%-9%. Risks for any diabetes complications were higher at an A1c level ≥ 8%. Another observational study reported a U-shaped association between A1c and mortality, with the lowest hazard ratio for mortality at an A1c level of about 7.5%. Similarly, the ACCORD trial, which included older and middle-aged patients with T2D who had or were at risk for atherosclerotic cardiovascular disease, found that mortality followed a U-shaped curve at the low (A1c < 7%) and high (A1c > 8%) ends in patients who were given standard glycemic therapy. Hence, there has been a general trend to recommend less strict glycemic control in older adults.

However, it is important to remember that older patients with T2D are a heterogeneous group. The spectrum includes adults with recent-onset diabetes with no or few complications, those with long-standing diabetes and many complications, and frail older adults with multiple comorbidities and complications. Determining the optimal glycemic target for an older patient with T2D requires assessment not only of the patient’s medical status and comorbidities but also functional status, cognitive and psychological health, social situation, individual preferences, and life expectancy. The American Diabetes Association Standards of Medical Care in Diabetes provides the following guidance in determining the optimal glycemic control for older adults:

• Healthy adults with few coexisting chronic illnesses and intact cognitive and functional status should have an A1c level < 7.0%-7.5%.
• Adults with complex or intermediate comorbidities (multiple coexisting chronic illnesses, or two or more instrumental activities of daily living impairments, or mild to moderate cognitive impairment) should have an A1c level < 8.0%.
• Patients with poor health (long-term care or end-stage chronic illnesses or moderate to severe cognitive impairment or two or more activities of daily living impairments) should avoid reliance on A1c, and the goal is to avoid hypoglycemia and symptomatic hyperglycemia.

Because older patients are at a higher risk for complications and adverse effects from polypharmacy, regular assessments are recommended and treatment plans should be routinely reviewed and modified to avoid overtreatment.
 

Lifestyle interventions and pharmacotherapy

Lifestyle interventions, such as exercise, optimal nutrition, and protein intake, are integral in treating older patients with T2D. Older adults should engage in regular exercise (that is, aerobic activity, weight-bearing exercise, or resistance training), and the activity should be customized to frailty status. Regular exercise improves insulin sensitivity and glucose control, enhances functional status, and provides cardiometabolic benefits. Optimal nutrition and adequate protein intake are also important to prevent the development or worsening of sarcopenia and frailty.

Several factors must be considered when choosing pharmacotherapy for T2D treatment in older adults. These patients are at higher risk for adverse reactions to medications that can trigger hypoglycemia and serious cardiovascular events, and worsen cognitive function. Therefore, side effects should always be reviewed when choosing antidiabetic drugs. The complexity of treatment plans needs to be matched with the patients’ self-management abilities and available social support. Medication costs and insurance coverage should be considered because many older adults live on a fixed income. Although limited, data exist on the safety and efficacy of some glucose-lowering agents in older adults, which can provide guidance for choosing the optimal therapy for these patients.

Among the insulin sensitizers, metformin is most commonly used because of its efficacy, low risk for hypoglycemia, and affordability. Metformin can be safely used in the setting of reduced renal function down to the estimated glomerular filtration rate ≥ 30 mL/min per 1.73 m². However, metformin should be avoided in patients with more advanced renal disease, liver failure, or heart failure. In older patients with T2D, potential concerns of metformin include gastrointestinal side effects, leading to reduced appetite, mild weight loss, and risk for vitamin B12 deficiency.

Pioglitazone, an oral antidiabetic in the thiazolidinedione (TZD) class, also targets insulin resistance and may provide some cardiovascular benefits. However, these agents are not commonly used in treating older patients with T2D owing to associated risk for edema, heart failure, osteoporosis/fractures, and bladder cancer.

Sulfonylureas and meglitinides are insulin secretagogues, which can promote insulin release independent of glucose levels. Sulfonylureas are typically avoided in older patients because they are associated with high risk for hypoglycemia. Meglitinides have a lower hypoglycemia risk than sulfonylureas because of their short duration of action; however, they are more expensive and require multiple daily administration, which can lead to issues with adherence.

Since 2008, there have been numerous cardiovascular outcomes trials assessing the safety and efficacy of T2D therapies that included a subpopulation of older patients either with cardiovascular disease or at high risk for cardiovascular disease. Post hoc analysis of data from these trials and smaller studies dedicated to older adults demonstrated the safety and efficacy of most incretin-based therapies and sodium-glucose cotransporter 2 (SGLT2) inhibitors in these patients. These newer medications have low hypoglycemia risk if not used in combination with insulin or insulin secretagogues.

Dipeptidyl peptidase 4 (DPP-4) inhibitors have the mildest side effect profile. However, they can be expensive and not reduce major adverse cardiovascular outcomes, and one agent, saxagliptin, has been associated with increased risk for heart failure hospitalization. Some glucagon-like peptide 1 (GLP-1) receptor agonists are effective in reducing major adverse cardiovascular events (cardiovascular deaths, stroke, and myocardial infarction) in patients older and younger than age 65. However, the gastrointestinal side effects and weight loss associated with this medication can be problematic for older patients. Most of the GLP-1 receptor agonists are injectables, which require good visual, motor, and cognitive skills for administration. SGLT2 inhibitors offer benefits for patients with T2D who have established cardiovascular disease, heart failure, and chronic kidney disease, with possible greater cardiovascular benefits in older adults. Adverse effects associated with SGLT2 inhibitors, such as weight loss, volume depletion, urinary incontinence, and genitourinary infections, may be a concern in older patients with T2D who are using these medications.

Because the insulin-secreting capacity of the pancreas declines with age, insulin therapy may be required for treatment of T2D in older patients. Insulin therapy can be complex and consideration must be given to patients’ social circumstances, as well as their physical and cognitive abilities. Older adults may need adaptive strategies, such as additional lighting, magnification glass, and premixed syringes. Simplification of complex insulin therapy (discontinuation of prandial insulin or sliding scale, changing timing of basal insulin) and use of insulin analogs with lower hypoglycemia risks should be considered. Weight gain as a result of insulin therapy may be beneficial in older adults with sarcopenia or frailty.
 

T2D technology for glycemic improvement

There have been major technological advancements in diabetes therapy. Continuous glucose monitors (CGMs) and automated insulin delivery systems can improve glycemic control, decrease the rate of hypoglycemia, and enhance the quality of life of older patients. Most of the studies evaluating the use of automated insulin delivery systems in older patients have focused on those with type 1 diabetes and demonstrated improvement in glycemic control and/or reduced hypoglycemia. The DIAMOND trial demonstrated improved A1c and reduced glycemic variability with the use of CGM in adults older than 60 years with either type 1 or type 2 diabetes on multiple daily injections. Bluetooth-enabled “smart” insulin pens, which record the time and dose of insulin administrations, can also be a great asset in caring for older patients, especially those with cognitive impairment. With better insurance coverage, diabetes technologies may become more accessible and an asset in treating older patients with T2D.

In conclusion, management of T2D in older adults requires an individualized approach because of the heterogeneity in their health and functional status. Because cardiovascular disease is the leading cause of mortality in older patients with T2D, treatment plans should also address frequently coexisting cardiovascular risk factors, such as hypertension and hyperlipidemia. Clinicians should consider patients’ overall health, comorbidities, cognitive and functional status, social support systems, preferences, and life expectancy when developing individualized therapeutic plans.

Dr. Gunawan is an assistant professor in the department of internal medicine at UT Southwestern Medical Center, Dallas. She reported no relevant conflicts of interest.

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

In the United States, type 2 diabetes (T2D) more commonly affects people older than 40 years, but it is most prevalent among adults over age 65, affecting more than 29% of this population. The heterogeneity in the health and functional status of older adults presents a challenge in the management and treatment of older patients with T2D. Moreover, there is an increased risk for health-related comorbidities and complications from diabetes treatment (for example, hypoglycemia) in older adults. Physiologic changes, such as decreased renal function, cognitive decline, and sarcopenia, may lead to an increased risk for adverse reactions to medications and require an individualized treatment approach. Although there have been a limited number of randomized controlled studies targeting older adults with multiple comorbidities and poor health status, subanalyses of diabetes trials with a subpopulation of older adults have provided additional evidence to better guide therapeutic approaches in caring for older patients with T2D.

Here’s a guide to developing personalized therapeutic regimens for older patients with T2D using lifestyle interventions, pharmacotherapy, and diabetes technology.
 

Determining an optimal glycemic target

An important first step in diabetes treatment is to determine the optimal glycemic target for patients. Although data support intensive glycemic control (hemoglobin A1c < 7%) to prevent complications from diabetes in younger patients with recently diagnosed disease, the data are less compelling in trials involving older populations with longer durations of T2D. One observational study with 71,092 older adults over age 60 reported a U-shaped correlation between A1c and mortality, with higher risks for mortality in those with A1c levels < 6% and ≥ 11%, compared with those with A1c levels of 6%-9%. Risks for any diabetes complications were higher at an A1c level ≥ 8%. Another observational study reported a U-shaped association between A1c and mortality, with the lowest hazard ratio for mortality at an A1c level of about 7.5%. Similarly, the ACCORD trial, which included older and middle-aged patients with T2D who had or were at risk for atherosclerotic cardiovascular disease, found that mortality followed a U-shaped curve at the low (A1c < 7%) and high (A1c > 8%) ends in patients who were given standard glycemic therapy. Hence, there has been a general trend to recommend less strict glycemic control in older adults.

However, it is important to remember that older patients with T2D are a heterogeneous group. The spectrum includes adults with recent-onset diabetes with no or few complications, those with long-standing diabetes and many complications, and frail older adults with multiple comorbidities and complications. Determining the optimal glycemic target for an older patient with T2D requires assessment not only of the patient’s medical status and comorbidities but also functional status, cognitive and psychological health, social situation, individual preferences, and life expectancy. The American Diabetes Association Standards of Medical Care in Diabetes provides the following guidance in determining the optimal glycemic control for older adults:

• Healthy adults with few coexisting chronic illnesses and intact cognitive and functional status should have an A1c level < 7.0%-7.5%.
• Adults with complex or intermediate comorbidities (multiple coexisting chronic illnesses, or two or more instrumental activities of daily living impairments, or mild to moderate cognitive impairment) should have an A1c level < 8.0%.
• Patients with poor health (long-term care or end-stage chronic illnesses or moderate to severe cognitive impairment or two or more activities of daily living impairments) should avoid reliance on A1c, and the goal is to avoid hypoglycemia and symptomatic hyperglycemia.

Because older patients are at a higher risk for complications and adverse effects from polypharmacy, regular assessments are recommended and treatment plans should be routinely reviewed and modified to avoid overtreatment.
 

Lifestyle interventions and pharmacotherapy

Lifestyle interventions, such as exercise, optimal nutrition, and protein intake, are integral in treating older patients with T2D. Older adults should engage in regular exercise (that is, aerobic activity, weight-bearing exercise, or resistance training), and the activity should be customized to frailty status. Regular exercise improves insulin sensitivity and glucose control, enhances functional status, and provides cardiometabolic benefits. Optimal nutrition and adequate protein intake are also important to prevent the development or worsening of sarcopenia and frailty.

Several factors must be considered when choosing pharmacotherapy for T2D treatment in older adults. These patients are at higher risk for adverse reactions to medications that can trigger hypoglycemia and serious cardiovascular events, and worsen cognitive function. Therefore, side effects should always be reviewed when choosing antidiabetic drugs. The complexity of treatment plans needs to be matched with the patients’ self-management abilities and available social support. Medication costs and insurance coverage should be considered because many older adults live on a fixed income. Although limited, data exist on the safety and efficacy of some glucose-lowering agents in older adults, which can provide guidance for choosing the optimal therapy for these patients.

Among the insulin sensitizers, metformin is most commonly used because of its efficacy, low risk for hypoglycemia, and affordability. Metformin can be safely used in the setting of reduced renal function down to the estimated glomerular filtration rate ≥ 30 mL/min per 1.73 m². However, metformin should be avoided in patients with more advanced renal disease, liver failure, or heart failure. In older patients with T2D, potential concerns of metformin include gastrointestinal side effects, leading to reduced appetite, mild weight loss, and risk for vitamin B12 deficiency.

Pioglitazone, an oral antidiabetic in the thiazolidinedione (TZD) class, also targets insulin resistance and may provide some cardiovascular benefits. However, these agents are not commonly used in treating older patients with T2D owing to associated risk for edema, heart failure, osteoporosis/fractures, and bladder cancer.

Sulfonylureas and meglitinides are insulin secretagogues, which can promote insulin release independent of glucose levels. Sulfonylureas are typically avoided in older patients because they are associated with high risk for hypoglycemia. Meglitinides have a lower hypoglycemia risk than sulfonylureas because of their short duration of action; however, they are more expensive and require multiple daily administration, which can lead to issues with adherence.

Since 2008, there have been numerous cardiovascular outcomes trials assessing the safety and efficacy of T2D therapies that included a subpopulation of older patients either with cardiovascular disease or at high risk for cardiovascular disease. Post hoc analysis of data from these trials and smaller studies dedicated to older adults demonstrated the safety and efficacy of most incretin-based therapies and sodium-glucose cotransporter 2 (SGLT2) inhibitors in these patients. These newer medications have low hypoglycemia risk if not used in combination with insulin or insulin secretagogues.

Dipeptidyl peptidase 4 (DPP-4) inhibitors have the mildest side effect profile. However, they can be expensive and not reduce major adverse cardiovascular outcomes, and one agent, saxagliptin, has been associated with increased risk for heart failure hospitalization. Some glucagon-like peptide 1 (GLP-1) receptor agonists are effective in reducing major adverse cardiovascular events (cardiovascular deaths, stroke, and myocardial infarction) in patients older and younger than age 65. However, the gastrointestinal side effects and weight loss associated with this medication can be problematic for older patients. Most of the GLP-1 receptor agonists are injectables, which require good visual, motor, and cognitive skills for administration. SGLT2 inhibitors offer benefits for patients with T2D who have established cardiovascular disease, heart failure, and chronic kidney disease, with possible greater cardiovascular benefits in older adults. Adverse effects associated with SGLT2 inhibitors, such as weight loss, volume depletion, urinary incontinence, and genitourinary infections, may be a concern in older patients with T2D who are using these medications.

Because the insulin-secreting capacity of the pancreas declines with age, insulin therapy may be required for treatment of T2D in older patients. Insulin therapy can be complex and consideration must be given to patients’ social circumstances, as well as their physical and cognitive abilities. Older adults may need adaptive strategies, such as additional lighting, magnification glass, and premixed syringes. Simplification of complex insulin therapy (discontinuation of prandial insulin or sliding scale, changing timing of basal insulin) and use of insulin analogs with lower hypoglycemia risks should be considered. Weight gain as a result of insulin therapy may be beneficial in older adults with sarcopenia or frailty.
 

T2D technology for glycemic improvement

There have been major technological advancements in diabetes therapy. Continuous glucose monitors (CGMs) and automated insulin delivery systems can improve glycemic control, decrease the rate of hypoglycemia, and enhance the quality of life of older patients. Most of the studies evaluating the use of automated insulin delivery systems in older patients have focused on those with type 1 diabetes and demonstrated improvement in glycemic control and/or reduced hypoglycemia. The DIAMOND trial demonstrated improved A1c and reduced glycemic variability with the use of CGM in adults older than 60 years with either type 1 or type 2 diabetes on multiple daily injections. Bluetooth-enabled “smart” insulin pens, which record the time and dose of insulin administrations, can also be a great asset in caring for older patients, especially those with cognitive impairment. With better insurance coverage, diabetes technologies may become more accessible and an asset in treating older patients with T2D.

In conclusion, management of T2D in older adults requires an individualized approach because of the heterogeneity in their health and functional status. Because cardiovascular disease is the leading cause of mortality in older patients with T2D, treatment plans should also address frequently coexisting cardiovascular risk factors, such as hypertension and hyperlipidemia. Clinicians should consider patients’ overall health, comorbidities, cognitive and functional status, social support systems, preferences, and life expectancy when developing individualized therapeutic plans.

Dr. Gunawan is an assistant professor in the department of internal medicine at UT Southwestern Medical Center, Dallas. She reported no relevant conflicts of interest.

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

In the United States, type 2 diabetes (T2D) more commonly affects people older than 40 years, but it is most prevalent among adults over age 65, affecting more than 29% of this population. The heterogeneity in the health and functional status of older adults presents a challenge in the management and treatment of older patients with T2D. Moreover, there is an increased risk for health-related comorbidities and complications from diabetes treatment (for example, hypoglycemia) in older adults. Physiologic changes, such as decreased renal function, cognitive decline, and sarcopenia, may lead to an increased risk for adverse reactions to medications and require an individualized treatment approach. Although there have been a limited number of randomized controlled studies targeting older adults with multiple comorbidities and poor health status, subanalyses of diabetes trials with a subpopulation of older adults have provided additional evidence to better guide therapeutic approaches in caring for older patients with T2D.

Here’s a guide to developing personalized therapeutic regimens for older patients with T2D using lifestyle interventions, pharmacotherapy, and diabetes technology.
 

Determining an optimal glycemic target

An important first step in diabetes treatment is to determine the optimal glycemic target for patients. Although data support intensive glycemic control (hemoglobin A1c < 7%) to prevent complications from diabetes in younger patients with recently diagnosed disease, the data are less compelling in trials involving older populations with longer durations of T2D. One observational study with 71,092 older adults over age 60 reported a U-shaped correlation between A1c and mortality, with higher risks for mortality in those with A1c levels < 6% and ≥ 11%, compared with those with A1c levels of 6%-9%. Risks for any diabetes complications were higher at an A1c level ≥ 8%. Another observational study reported a U-shaped association between A1c and mortality, with the lowest hazard ratio for mortality at an A1c level of about 7.5%. Similarly, the ACCORD trial, which included older and middle-aged patients with T2D who had or were at risk for atherosclerotic cardiovascular disease, found that mortality followed a U-shaped curve at the low (A1c < 7%) and high (A1c > 8%) ends in patients who were given standard glycemic therapy. Hence, there has been a general trend to recommend less strict glycemic control in older adults.

However, it is important to remember that older patients with T2D are a heterogeneous group. The spectrum includes adults with recent-onset diabetes with no or few complications, those with long-standing diabetes and many complications, and frail older adults with multiple comorbidities and complications. Determining the optimal glycemic target for an older patient with T2D requires assessment not only of the patient’s medical status and comorbidities but also functional status, cognitive and psychological health, social situation, individual preferences, and life expectancy. The American Diabetes Association Standards of Medical Care in Diabetes provides the following guidance in determining the optimal glycemic control for older adults:

• Healthy adults with few coexisting chronic illnesses and intact cognitive and functional status should have an A1c level < 7.0%-7.5%.
• Adults with complex or intermediate comorbidities (multiple coexisting chronic illnesses, or two or more instrumental activities of daily living impairments, or mild to moderate cognitive impairment) should have an A1c level < 8.0%.
• Patients with poor health (long-term care or end-stage chronic illnesses or moderate to severe cognitive impairment or two or more activities of daily living impairments) should avoid reliance on A1c, and the goal is to avoid hypoglycemia and symptomatic hyperglycemia.

Because older patients are at a higher risk for complications and adverse effects from polypharmacy, regular assessments are recommended and treatment plans should be routinely reviewed and modified to avoid overtreatment.
 

Lifestyle interventions and pharmacotherapy

Lifestyle interventions, such as exercise, optimal nutrition, and protein intake, are integral in treating older patients with T2D. Older adults should engage in regular exercise (that is, aerobic activity, weight-bearing exercise, or resistance training), and the activity should be customized to frailty status. Regular exercise improves insulin sensitivity and glucose control, enhances functional status, and provides cardiometabolic benefits. Optimal nutrition and adequate protein intake are also important to prevent the development or worsening of sarcopenia and frailty.

Several factors must be considered when choosing pharmacotherapy for T2D treatment in older adults. These patients are at higher risk for adverse reactions to medications that can trigger hypoglycemia and serious cardiovascular events, and worsen cognitive function. Therefore, side effects should always be reviewed when choosing antidiabetic drugs. The complexity of treatment plans needs to be matched with the patients’ self-management abilities and available social support. Medication costs and insurance coverage should be considered because many older adults live on a fixed income. Although limited, data exist on the safety and efficacy of some glucose-lowering agents in older adults, which can provide guidance for choosing the optimal therapy for these patients.

Among the insulin sensitizers, metformin is most commonly used because of its efficacy, low risk for hypoglycemia, and affordability. Metformin can be safely used in the setting of reduced renal function down to the estimated glomerular filtration rate ≥ 30 mL/min per 1.73 m². However, metformin should be avoided in patients with more advanced renal disease, liver failure, or heart failure. In older patients with T2D, potential concerns of metformin include gastrointestinal side effects, leading to reduced appetite, mild weight loss, and risk for vitamin B12 deficiency.

Pioglitazone, an oral antidiabetic in the thiazolidinedione (TZD) class, also targets insulin resistance and may provide some cardiovascular benefits. However, these agents are not commonly used in treating older patients with T2D owing to associated risk for edema, heart failure, osteoporosis/fractures, and bladder cancer.

Sulfonylureas and meglitinides are insulin secretagogues, which can promote insulin release independent of glucose levels. Sulfonylureas are typically avoided in older patients because they are associated with high risk for hypoglycemia. Meglitinides have a lower hypoglycemia risk than sulfonylureas because of their short duration of action; however, they are more expensive and require multiple daily administration, which can lead to issues with adherence.

Since 2008, there have been numerous cardiovascular outcomes trials assessing the safety and efficacy of T2D therapies that included a subpopulation of older patients either with cardiovascular disease or at high risk for cardiovascular disease. Post hoc analysis of data from these trials and smaller studies dedicated to older adults demonstrated the safety and efficacy of most incretin-based therapies and sodium-glucose cotransporter 2 (SGLT2) inhibitors in these patients. These newer medications have low hypoglycemia risk if not used in combination with insulin or insulin secretagogues.

Dipeptidyl peptidase 4 (DPP-4) inhibitors have the mildest side effect profile. However, they can be expensive and not reduce major adverse cardiovascular outcomes, and one agent, saxagliptin, has been associated with increased risk for heart failure hospitalization. Some glucagon-like peptide 1 (GLP-1) receptor agonists are effective in reducing major adverse cardiovascular events (cardiovascular deaths, stroke, and myocardial infarction) in patients older and younger than age 65. However, the gastrointestinal side effects and weight loss associated with this medication can be problematic for older patients. Most of the GLP-1 receptor agonists are injectables, which require good visual, motor, and cognitive skills for administration. SGLT2 inhibitors offer benefits for patients with T2D who have established cardiovascular disease, heart failure, and chronic kidney disease, with possible greater cardiovascular benefits in older adults. Adverse effects associated with SGLT2 inhibitors, such as weight loss, volume depletion, urinary incontinence, and genitourinary infections, may be a concern in older patients with T2D who are using these medications.

Because the insulin-secreting capacity of the pancreas declines with age, insulin therapy may be required for treatment of T2D in older patients. Insulin therapy can be complex and consideration must be given to patients’ social circumstances, as well as their physical and cognitive abilities. Older adults may need adaptive strategies, such as additional lighting, magnification glass, and premixed syringes. Simplification of complex insulin therapy (discontinuation of prandial insulin or sliding scale, changing timing of basal insulin) and use of insulin analogs with lower hypoglycemia risks should be considered. Weight gain as a result of insulin therapy may be beneficial in older adults with sarcopenia or frailty.
 

T2D technology for glycemic improvement

There have been major technological advancements in diabetes therapy. Continuous glucose monitors (CGMs) and automated insulin delivery systems can improve glycemic control, decrease the rate of hypoglycemia, and enhance the quality of life of older patients. Most of the studies evaluating the use of automated insulin delivery systems in older patients have focused on those with type 1 diabetes and demonstrated improvement in glycemic control and/or reduced hypoglycemia. The DIAMOND trial demonstrated improved A1c and reduced glycemic variability with the use of CGM in adults older than 60 years with either type 1 or type 2 diabetes on multiple daily injections. Bluetooth-enabled “smart” insulin pens, which record the time and dose of insulin administrations, can also be a great asset in caring for older patients, especially those with cognitive impairment. With better insurance coverage, diabetes technologies may become more accessible and an asset in treating older patients with T2D.

In conclusion, management of T2D in older adults requires an individualized approach because of the heterogeneity in their health and functional status. Because cardiovascular disease is the leading cause of mortality in older patients with T2D, treatment plans should also address frequently coexisting cardiovascular risk factors, such as hypertension and hyperlipidemia. Clinicians should consider patients’ overall health, comorbidities, cognitive and functional status, social support systems, preferences, and life expectancy when developing individualized therapeutic plans.

Dr. Gunawan is an assistant professor in the department of internal medicine at UT Southwestern Medical Center, Dallas. She reported no relevant conflicts of interest.

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

MONTPELLIER, FRANCE – The first expert consensus on smoking and diabetes, coauthored by the Francophone Diabetes Society (SFD) and the French Society for the Study of Nicotine Addiction (SFT), was presented at the SFD’s annual conference.

Alexia Rouland, MD, an endocrinologist at Dijon Bourgogne University Hospital, Dijon, France, took the conference as an opportunity to list the many benefits of smoking cessation for patients with diabetes, despite the “slight and temporary” risk for blood sugar imbalance.
 

Societies target smoking

Diabetes societies around Europe have set their sights on the topic of smoking. Indeed, the guidelines published in 2019 by the European Association for the Study of Diabetes and the European Society of Cardiology state that “smoking cessation is obligatory for all prediabetic and diabetic patients” (class I, level A).

This year, the France-based SFD and SFT dedicated an expert consensus to the major problem of smoking in patients with diabetes. The aim was to provide health care professionals with convincing, well-supported arguments in favor of smoking cessation in their patients with type 1 and type 2 diabetes.

“Before anything else, diabetic patients need to be made aware of the risks of smoking,” said Dr. Rouland. “It’s not just about the fear factor, though. It’s also about providing a positive incentive – they need to be told about the ways they’ll benefit from quitting smoking. For example, you have all-cause mortality, macro- and microangiopathic complications, and so on.”
 

Duration of abstinence

“Diabetic patients who have stopped smoking have a relative risk for all-cause mortality of 1.28 (1.09-1.51), which is less than what you see in active smokers (relative risk = 1.58; 1.42-1.77), but still above that of nonsmokers,” said Dr. Rouland.

A previous study revealed that although the risk does indeed go down after stopping smoking, it is linked to how long ago the person stopped. Patients who stopped smoking less than 10 years ago still had a slightly raised all-cause mortality risk, and this was even higher if they had smoked for 20 years or more.

After 10 years of not smoking, however, the greater all-cause mortality risk was no longer significant in any of the groups monitored (smoking duration, number of cigarettes/day). Concrete evidence of the link between all-cause mortality and the length of time since a person stopped smoking also emerged from the large cohort in the American Nurses’ Health Study.

The relative risk for all-cause mortality in women who stopped smoking less than 5 years ago remained high (RR = 1.96, 1.47-2.67), then decreased over time. After 10 years, it was no longer significant (RR = 1.11, 0.92-1.35).
 

Macro- and microangiopathic risks

Smoking cessation also has a real benefit in terms of the increased macro- and microangiopathic risks. In type 2 diabetes, a study found an increased relative risk for macro- and microalbuminuria of 1.86 (95% confidence interval, 1.37-2.52) in former smokers, compared with an increased relative risk of 2.61 (95% CI, 1.86-2.64) in current smokers.

In type 1 diabetes, the cumulative risk for microalbuminuria in former smokers was 15.1% vs. 18.9% in smokers and 10% in nonsmokers.

A 2019 meta-analysis of prospective cohort studies determined that smoking is an independent risk factor for diabetic nephropathy, especially in patients with type 1 diabetes.

Yet, most of the data for this condition come from subjects with type 2 diabetes. One publication estimated its prevalence after a 1-year follow-up of the smoking cessation program as 10.9% in former smokers and 15% in those who continued smoking.

In regard to macroangiopathy in the context of type 2 diabetes, the aforementioned 2019 meta-analysis focused on coronary artery disease, cerebrovascular accident (CVA), cardiovascular mortality, and myocardial infarction (MI). It found that smokers face an increased risk for all these outcomes.

The relative risks wavered between 1.53 and 1.66 and decreased after smoking cessation. For coronary artery disease and MI, they became insignificant. There was still a risk for CVA (RR = 1.34; 1.07-1.67) and fatal cardiovascular events (RR = 1.19; 0.02-1.39).

The data are slightly more heterogeneous for type 1 diabetes, where, despite smoking cessation, the increased risk for heart failure and CVA persists in men, yet the same risk for coronary heart disease and CVA drops in women.
 

Risk for weight gain

Dr. Rouland tried to reassure patients about the risk for gaining weight. “Weight gain is not inevitable. There is a risk for this, but it’s temporary. And, even with some weight gain, the cardiovascular benefits are still indisputable.”

A study carried out in 2013 focused specifically on this point, with an average post-cessation weight gain of 3.8 kg (8.4 lb) seen in diabetic individuals in the first 4 years after stopping smoking and of 0.1 kg (0.2 lb) thereafter. A time-based effect was observed with regulation of excess weight post-cessation over time, as seen in the general population (3 kg [6.6 lb] on average in nondiabetic individuals).

Weight gain tends to occur mainly in the immediate post-cessation period, essentially in the first 3 months, and there is a large variation in weight change. Some people gain a lot (from 5 to 10 kg [11 to 22 lb], or even more than 10 kg); others lose weight (20% of diabetic former smokers in the first month, 7% after 12 months), and 25% gain less than 5 kg (11 lb).
 

Blood glucose imbalance

“A risk for blood glucose imbalance has been reported after smoking cessation, although this is very slight and only temporary,” said Dr. Rouland.

A British retrospective study examined this question, focusing on glycated hemoglobin in patients with type 2 diabetes. Hemoglobin A1c increased by 0.21% (95% CI, 0.17-0.25; P < .001) within the first year after quitting. A1c decreased as abstinence continued and became comparable to that of continual smokers after 3 years. This increase in A1c was not mediated by weight change.

Another study published in 2018 on the topic of type 2 diabetes also reported on the risk for poor glycemic control (defined as A1c > 7%) persisting for 10 years after smoking cessation (odds ratio, 1.23; 95% CI, 1.06-1.42). Thereafter, between 10 and 19 years post-cessation, the OR decreased to 0.97 (95% CI, 0.80-1.19, NS). Beyond 20 years post-cessation, the OR was 1.14 (95% CI, 0.89-1.44, NS) and was therefore no longer significant.

Regardless, “the risk for poor glycemic control is lower in quitters than in active smokers,” said Dr. Rouland.
 

Quitting and diabetes risk

Will a smoker’s increased risk for diabetes drop when he or she stops smoking? “This is essentially what happens,” Dr. Rouland confirmed, “and his or her increased risk for metabolic syndrome also drops. One meta-analysis revealed a time-based effect.

“Patients who had stopped smoking less than 5 years previously had an increased relative risk for type 2 diabetes, and this risk dropped to 1.11 after more than 10 years of not smoking. Moreover, this relative risk for type 2 diabetes remained lower than that of active smokers, at between 1.19 and 1.60, depending on tobacco use.”

In regard to the risk for metabolic syndrome, those who quit smoking seem to have an increased risk of 10%, compared with nonsmokers (RR = 1.10, 1.08-1.11; P < .001). “But yet again, this increased risk is much lower than that of active smokers, whose risk is between 37% (less than 20 cigarettes/day) and 71% (more than 20 cigarettes/day).”
 

Women with diabetes

“The benefits of quitting appear identical, regardless of the sex of the diabetic person,” said Dr. Rouland. “As in the general population, weight gain after smoking cessation is greater in women. Furthermore, while smoking increases the risk for gestational diabetes (RR, 1.4-1.9) and for the use of insulin in this context, stopping smoking reduces these risks.

“Moreover, smoking during pregnancy not only increases the risk for pregnancy-related complications (early miscarriage, ectopic pregnancy, birth defects, placental abruption, premature birth, intrauterine fetal demise, cesarean birth, low birth weight), but it also increases the risk of type 2 diabetes in the newborn. The risk to the newborn is said to be around 34% in cases in which the mother smokes during pregnancy and 22% in cases in which the mother is a passive smoker, thereby justifying the use of measures to help the mother’s family members to stop smoking.”

Dr. Rouland reports no relevant financial relationships.

This article was translated from the Medscape French edition. A version appeared on Medscape.com.

MONTPELLIER, FRANCE – The first expert consensus on smoking and diabetes, coauthored by the Francophone Diabetes Society (SFD) and the French Society for the Study of Nicotine Addiction (SFT), was presented at the SFD’s annual conference.

Alexia Rouland, MD, an endocrinologist at Dijon Bourgogne University Hospital, Dijon, France, took the conference as an opportunity to list the many benefits of smoking cessation for patients with diabetes, despite the “slight and temporary” risk for blood sugar imbalance.
 

Societies target smoking

Diabetes societies around Europe have set their sights on the topic of smoking. Indeed, the guidelines published in 2019 by the European Association for the Study of Diabetes and the European Society of Cardiology state that “smoking cessation is obligatory for all prediabetic and diabetic patients” (class I, level A).

This year, the France-based SFD and SFT dedicated an expert consensus to the major problem of smoking in patients with diabetes. The aim was to provide health care professionals with convincing, well-supported arguments in favor of smoking cessation in their patients with type 1 and type 2 diabetes.

“Before anything else, diabetic patients need to be made aware of the risks of smoking,” said Dr. Rouland. “It’s not just about the fear factor, though. It’s also about providing a positive incentive – they need to be told about the ways they’ll benefit from quitting smoking. For example, you have all-cause mortality, macro- and microangiopathic complications, and so on.”
 

Duration of abstinence

“Diabetic patients who have stopped smoking have a relative risk for all-cause mortality of 1.28 (1.09-1.51), which is less than what you see in active smokers (relative risk = 1.58; 1.42-1.77), but still above that of nonsmokers,” said Dr. Rouland.

A previous study revealed that although the risk does indeed go down after stopping smoking, it is linked to how long ago the person stopped. Patients who stopped smoking less than 10 years ago still had a slightly raised all-cause mortality risk, and this was even higher if they had smoked for 20 years or more.

After 10 years of not smoking, however, the greater all-cause mortality risk was no longer significant in any of the groups monitored (smoking duration, number of cigarettes/day). Concrete evidence of the link between all-cause mortality and the length of time since a person stopped smoking also emerged from the large cohort in the American Nurses’ Health Study.

The relative risk for all-cause mortality in women who stopped smoking less than 5 years ago remained high (RR = 1.96, 1.47-2.67), then decreased over time. After 10 years, it was no longer significant (RR = 1.11, 0.92-1.35).
 

Macro- and microangiopathic risks

Smoking cessation also has a real benefit in terms of the increased macro- and microangiopathic risks. In type 2 diabetes, a study found an increased relative risk for macro- and microalbuminuria of 1.86 (95% confidence interval, 1.37-2.52) in former smokers, compared with an increased relative risk of 2.61 (95% CI, 1.86-2.64) in current smokers.

In type 1 diabetes, the cumulative risk for microalbuminuria in former smokers was 15.1% vs. 18.9% in smokers and 10% in nonsmokers.

A 2019 meta-analysis of prospective cohort studies determined that smoking is an independent risk factor for diabetic nephropathy, especially in patients with type 1 diabetes.

Yet, most of the data for this condition come from subjects with type 2 diabetes. One publication estimated its prevalence after a 1-year follow-up of the smoking cessation program as 10.9% in former smokers and 15% in those who continued smoking.

In regard to macroangiopathy in the context of type 2 diabetes, the aforementioned 2019 meta-analysis focused on coronary artery disease, cerebrovascular accident (CVA), cardiovascular mortality, and myocardial infarction (MI). It found that smokers face an increased risk for all these outcomes.

The relative risks wavered between 1.53 and 1.66 and decreased after smoking cessation. For coronary artery disease and MI, they became insignificant. There was still a risk for CVA (RR = 1.34; 1.07-1.67) and fatal cardiovascular events (RR = 1.19; 0.02-1.39).

The data are slightly more heterogeneous for type 1 diabetes, where, despite smoking cessation, the increased risk for heart failure and CVA persists in men, yet the same risk for coronary heart disease and CVA drops in women.
 

Risk for weight gain

Dr. Rouland tried to reassure patients about the risk for gaining weight. “Weight gain is not inevitable. There is a risk for this, but it’s temporary. And, even with some weight gain, the cardiovascular benefits are still indisputable.”

A study carried out in 2013 focused specifically on this point, with an average post-cessation weight gain of 3.8 kg (8.4 lb) seen in diabetic individuals in the first 4 years after stopping smoking and of 0.1 kg (0.2 lb) thereafter. A time-based effect was observed with regulation of excess weight post-cessation over time, as seen in the general population (3 kg [6.6 lb] on average in nondiabetic individuals).

Weight gain tends to occur mainly in the immediate post-cessation period, essentially in the first 3 months, and there is a large variation in weight change. Some people gain a lot (from 5 to 10 kg [11 to 22 lb], or even more than 10 kg); others lose weight (20% of diabetic former smokers in the first month, 7% after 12 months), and 25% gain less than 5 kg (11 lb).
 

Blood glucose imbalance

“A risk for blood glucose imbalance has been reported after smoking cessation, although this is very slight and only temporary,” said Dr. Rouland.

A British retrospective study examined this question, focusing on glycated hemoglobin in patients with type 2 diabetes. Hemoglobin A1c increased by 0.21% (95% CI, 0.17-0.25; P < .001) within the first year after quitting. A1c decreased as abstinence continued and became comparable to that of continual smokers after 3 years. This increase in A1c was not mediated by weight change.

Another study published in 2018 on the topic of type 2 diabetes also reported on the risk for poor glycemic control (defined as A1c > 7%) persisting for 10 years after smoking cessation (odds ratio, 1.23; 95% CI, 1.06-1.42). Thereafter, between 10 and 19 years post-cessation, the OR decreased to 0.97 (95% CI, 0.80-1.19, NS). Beyond 20 years post-cessation, the OR was 1.14 (95% CI, 0.89-1.44, NS) and was therefore no longer significant.

Regardless, “the risk for poor glycemic control is lower in quitters than in active smokers,” said Dr. Rouland.
 

Quitting and diabetes risk

Will a smoker’s increased risk for diabetes drop when he or she stops smoking? “This is essentially what happens,” Dr. Rouland confirmed, “and his or her increased risk for metabolic syndrome also drops. One meta-analysis revealed a time-based effect.

“Patients who had stopped smoking less than 5 years previously had an increased relative risk for type 2 diabetes, and this risk dropped to 1.11 after more than 10 years of not smoking. Moreover, this relative risk for type 2 diabetes remained lower than that of active smokers, at between 1.19 and 1.60, depending on tobacco use.”

In regard to the risk for metabolic syndrome, those who quit smoking seem to have an increased risk of 10%, compared with nonsmokers (RR = 1.10, 1.08-1.11; P < .001). “But yet again, this increased risk is much lower than that of active smokers, whose risk is between 37% (less than 20 cigarettes/day) and 71% (more than 20 cigarettes/day).”
 

Women with diabetes

“The benefits of quitting appear identical, regardless of the sex of the diabetic person,” said Dr. Rouland. “As in the general population, weight gain after smoking cessation is greater in women. Furthermore, while smoking increases the risk for gestational diabetes (RR, 1.4-1.9) and for the use of insulin in this context, stopping smoking reduces these risks.

“Moreover, smoking during pregnancy not only increases the risk for pregnancy-related complications (early miscarriage, ectopic pregnancy, birth defects, placental abruption, premature birth, intrauterine fetal demise, cesarean birth, low birth weight), but it also increases the risk of type 2 diabetes in the newborn. The risk to the newborn is said to be around 34% in cases in which the mother smokes during pregnancy and 22% in cases in which the mother is a passive smoker, thereby justifying the use of measures to help the mother’s family members to stop smoking.”

Dr. Rouland reports no relevant financial relationships.

This article was translated from the Medscape French edition. A version appeared on Medscape.com.

MONTPELLIER, FRANCE – The first expert consensus on smoking and diabetes, coauthored by the Francophone Diabetes Society (SFD) and the French Society for the Study of Nicotine Addiction (SFT), was presented at the SFD’s annual conference.

Alexia Rouland, MD, an endocrinologist at Dijon Bourgogne University Hospital, Dijon, France, took the conference as an opportunity to list the many benefits of smoking cessation for patients with diabetes, despite the “slight and temporary” risk for blood sugar imbalance.
 

Societies target smoking

Diabetes societies around Europe have set their sights on the topic of smoking. Indeed, the guidelines published in 2019 by the European Association for the Study of Diabetes and the European Society of Cardiology state that “smoking cessation is obligatory for all prediabetic and diabetic patients” (class I, level A).

This year, the France-based SFD and SFT dedicated an expert consensus to the major problem of smoking in patients with diabetes. The aim was to provide health care professionals with convincing, well-supported arguments in favor of smoking cessation in their patients with type 1 and type 2 diabetes.

“Before anything else, diabetic patients need to be made aware of the risks of smoking,” said Dr. Rouland. “It’s not just about the fear factor, though. It’s also about providing a positive incentive – they need to be told about the ways they’ll benefit from quitting smoking. For example, you have all-cause mortality, macro- and microangiopathic complications, and so on.”
 

Duration of abstinence

“Diabetic patients who have stopped smoking have a relative risk for all-cause mortality of 1.28 (1.09-1.51), which is less than what you see in active smokers (relative risk = 1.58; 1.42-1.77), but still above that of nonsmokers,” said Dr. Rouland.

A previous study revealed that although the risk does indeed go down after stopping smoking, it is linked to how long ago the person stopped. Patients who stopped smoking less than 10 years ago still had a slightly raised all-cause mortality risk, and this was even higher if they had smoked for 20 years or more.

After 10 years of not smoking, however, the greater all-cause mortality risk was no longer significant in any of the groups monitored (smoking duration, number of cigarettes/day). Concrete evidence of the link between all-cause mortality and the length of time since a person stopped smoking also emerged from the large cohort in the American Nurses’ Health Study.

The relative risk for all-cause mortality in women who stopped smoking less than 5 years ago remained high (RR = 1.96, 1.47-2.67), then decreased over time. After 10 years, it was no longer significant (RR = 1.11, 0.92-1.35).
 

Macro- and microangiopathic risks

Smoking cessation also has a real benefit in terms of the increased macro- and microangiopathic risks. In type 2 diabetes, a study found an increased relative risk for macro- and microalbuminuria of 1.86 (95% confidence interval, 1.37-2.52) in former smokers, compared with an increased relative risk of 2.61 (95% CI, 1.86-2.64) in current smokers.

In type 1 diabetes, the cumulative risk for microalbuminuria in former smokers was 15.1% vs. 18.9% in smokers and 10% in nonsmokers.

A 2019 meta-analysis of prospective cohort studies determined that smoking is an independent risk factor for diabetic nephropathy, especially in patients with type 1 diabetes.

Yet, most of the data for this condition come from subjects with type 2 diabetes. One publication estimated its prevalence after a 1-year follow-up of the smoking cessation program as 10.9% in former smokers and 15% in those who continued smoking.

In regard to macroangiopathy in the context of type 2 diabetes, the aforementioned 2019 meta-analysis focused on coronary artery disease, cerebrovascular accident (CVA), cardiovascular mortality, and myocardial infarction (MI). It found that smokers face an increased risk for all these outcomes.

The relative risks wavered between 1.53 and 1.66 and decreased after smoking cessation. For coronary artery disease and MI, they became insignificant. There was still a risk for CVA (RR = 1.34; 1.07-1.67) and fatal cardiovascular events (RR = 1.19; 0.02-1.39).

The data are slightly more heterogeneous for type 1 diabetes, where, despite smoking cessation, the increased risk for heart failure and CVA persists in men, yet the same risk for coronary heart disease and CVA drops in women.
 

Risk for weight gain

Dr. Rouland tried to reassure patients about the risk for gaining weight. “Weight gain is not inevitable. There is a risk for this, but it’s temporary. And, even with some weight gain, the cardiovascular benefits are still indisputable.”

A study carried out in 2013 focused specifically on this point, with an average post-cessation weight gain of 3.8 kg (8.4 lb) seen in diabetic individuals in the first 4 years after stopping smoking and of 0.1 kg (0.2 lb) thereafter. A time-based effect was observed with regulation of excess weight post-cessation over time, as seen in the general population (3 kg [6.6 lb] on average in nondiabetic individuals).

Weight gain tends to occur mainly in the immediate post-cessation period, essentially in the first 3 months, and there is a large variation in weight change. Some people gain a lot (from 5 to 10 kg [11 to 22 lb], or even more than 10 kg); others lose weight (20% of diabetic former smokers in the first month, 7% after 12 months), and 25% gain less than 5 kg (11 lb).
 

Blood glucose imbalance

“A risk for blood glucose imbalance has been reported after smoking cessation, although this is very slight and only temporary,” said Dr. Rouland.

A British retrospective study examined this question, focusing on glycated hemoglobin in patients with type 2 diabetes. Hemoglobin A1c increased by 0.21% (95% CI, 0.17-0.25; P < .001) within the first year after quitting. A1c decreased as abstinence continued and became comparable to that of continual smokers after 3 years. This increase in A1c was not mediated by weight change.

Another study published in 2018 on the topic of type 2 diabetes also reported on the risk for poor glycemic control (defined as A1c > 7%) persisting for 10 years after smoking cessation (odds ratio, 1.23; 95% CI, 1.06-1.42). Thereafter, between 10 and 19 years post-cessation, the OR decreased to 0.97 (95% CI, 0.80-1.19, NS). Beyond 20 years post-cessation, the OR was 1.14 (95% CI, 0.89-1.44, NS) and was therefore no longer significant.

Regardless, “the risk for poor glycemic control is lower in quitters than in active smokers,” said Dr. Rouland.
 

Quitting and diabetes risk

Will a smoker’s increased risk for diabetes drop when he or she stops smoking? “This is essentially what happens,” Dr. Rouland confirmed, “and his or her increased risk for metabolic syndrome also drops. One meta-analysis revealed a time-based effect.

“Patients who had stopped smoking less than 5 years previously had an increased relative risk for type 2 diabetes, and this risk dropped to 1.11 after more than 10 years of not smoking. Moreover, this relative risk for type 2 diabetes remained lower than that of active smokers, at between 1.19 and 1.60, depending on tobacco use.”

In regard to the risk for metabolic syndrome, those who quit smoking seem to have an increased risk of 10%, compared with nonsmokers (RR = 1.10, 1.08-1.11; P < .001). “But yet again, this increased risk is much lower than that of active smokers, whose risk is between 37% (less than 20 cigarettes/day) and 71% (more than 20 cigarettes/day).”
 

Women with diabetes

“The benefits of quitting appear identical, regardless of the sex of the diabetic person,” said Dr. Rouland. “As in the general population, weight gain after smoking cessation is greater in women. Furthermore, while smoking increases the risk for gestational diabetes (RR, 1.4-1.9) and for the use of insulin in this context, stopping smoking reduces these risks.

“Moreover, smoking during pregnancy not only increases the risk for pregnancy-related complications (early miscarriage, ectopic pregnancy, birth defects, placental abruption, premature birth, intrauterine fetal demise, cesarean birth, low birth weight), but it also increases the risk of type 2 diabetes in the newborn. The risk to the newborn is said to be around 34% in cases in which the mother smokes during pregnancy and 22% in cases in which the mother is a passive smoker, thereby justifying the use of measures to help the mother’s family members to stop smoking.”

Dr. Rouland reports no relevant financial relationships.

This article was translated from the Medscape French edition. A version appeared on Medscape.com.