Nadine Eckert

According to a US cross-sectional study, every fifth hospital patient with a respiratory syncytial virus (RSV) infection develops an acute cardiovascular event. For patients with a preexisting cardiovascular condition, an acute cardiovascular event occurs in every third patient, as shown by data published in JAMA Internal Medicine.

RSV attacks the respiratory tract, especially the mucous membranes of the upper airways and the ciliated epithelium of the trachea and bronchi. It is not the first respiratory virus with devastating consequences for the cardiovascular system.

“In the COVID-19 pandemic, we painfully learned that patients with preexisting cardiovascular conditions have significantly higher mortality rates and that cardiovascular causes are essential in COVID-19 mortality,” said Stephan Baldus, MD, director of Clinic III for Internal Medicine at the Heart Center of the University Hospital Cologne in Cologne, Germany.

“A direct link between the virus and the development of acute coronary events has also been demonstrated for influenza. Studies have shown that in the early days of an influenza infection, the rates of heart attacks and subsequent deaths increase significantly,” Dr. Baldus added. “And now, this study shows that patients with cardiovascular diseases have a critically increased risk for an acute cardiovascular event during an RSV infection.”
 

RSV Surveillance

Rebecca C. Woodruff, PhD, of the Centers for Disease Control and Prevention in Atlanta, and her colleagues analyzed data from an RSV surveillance program involving hospitals in 12 US states. The data covered hospitalized adults aged 50 years and older from five RSV seasons (from 2014/2015 to 2017/2018 and 2022/2023).

The 6248 patients were hospitalized for various reasons. They had a mean age of 73 years, and 60% of them were women. RSV infection was detected through a physician-ordered test within 14 days of admission. Slightly more than half (56.4%) of the patients had a preexisting cardiovascular condition that did not necessitate hospital treatment.

The researchers reported that more than a fifth (22.4%) of the patients with RSV had an acute cardiovascular event. Acute heart failure was most common (15.8%), but there were also acute ischemic heart disease in 7.5%, hypertensive crisis in 1.3%, ventricular tachycardia in 1.1%, and cardiogenic shock in 0.6%.
 

Acute Cardiovascular Events

Among the study population, 8.5% had no documented cardiovascular preexisting conditions. However, the risk was particularly elevated in patients with cardiovascular preexisting conditions. Overall, 33.0% of them had an acute cardiovascular event during the RSV infection.

Patients with acute cardiovascular events were almost twice as likely to have a severe course as those without acute cardiovascular events. The researchers considered treatment in the intensive care unit, the need for invasive mechanical ventilation, or the patient’s death in the hospital as severe outcomes.

Of all hospitalized patients with RSV, 18.6% required intensive care unit treatment, and 4.9% died during hospitalization. Compared with those without acute cardiovascular events, those with acute cardiovascular events had a significantly higher risk for intensive care treatment (25.8% vs 16.5%) and death in the hospital (8.1% vs 4.0%).

Although the analysis is not a prospective controlled study, according to Dr. Baldus, the results strongly suggest that RSV has cardiovascular effects. “When one in five hospitalized patients develops a cardiovascular event, that’s very suggestive,” he said.
 

More Testing Needed?

The results add to the evidence that RSV infections in older patients are associated with considerable morbidity and mortality. Unlike for COVID-19 and influenza, however, there is hardly any surveillance for RSV infections. RSV testing in hospitals is rare. Many doctors opt against testing for RSV because they are not aware of the importance of RSV as a pathogen in adults, but also because the diagnosis of RSV has no therapeutic consequences, wrote Dr. Woodruff and her colleagues.

Because there is no targeted therapy for an RSV infection, the detection of RSV can only be used as a marker for a risk for the development of an acute cardiovascular event, according to Dr. Baldus. Even considering the new study data, he emphasized, “Not every patient with a cardiovascular preexisting condition needs to be tested for RSV.”

The crucial factor is the clinical presentation. “If there is a clinical indication of pulmonary impairment (shortness of breath, tachypnea, subfebrile temperatures, or a diminished general condition) it would be desirable to perform an RSV test. This is especially true for patients requiring intensive care who need respiratory support,” said Dr. Baldus.
 

Benefits of Vaccination

The results highlight the basic epidemiology of potential cardiovascular complications of RSV infections, but before RSV vaccination became available, wrote Dr. Woodruff and her colleagues.

In 2023, the first RSV vaccine for adults aged 60 years and older was approved. “Here, a door to additional possibilities opens,” said Dr. Baldus. Although there are currently no official vaccination recommendations from Germany’s Standing Vaccination Commission, medical societies of oncologists and pulmonologists recommend vaccination against RSV. “Given the relevance of cardiovascular diseases for the prognosis of patients, but also for the occurrence of an acute cardiovascular event upon detection of RSV, the corresponding recommendation is expected to come,” said Dr. Baldus.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

According to a US cross-sectional study, every fifth hospital patient with a respiratory syncytial virus (RSV) infection develops an acute cardiovascular event. For patients with a preexisting cardiovascular condition, an acute cardiovascular event occurs in every third patient, as shown by data published in JAMA Internal Medicine.

RSV attacks the respiratory tract, especially the mucous membranes of the upper airways and the ciliated epithelium of the trachea and bronchi. It is not the first respiratory virus with devastating consequences for the cardiovascular system.

“In the COVID-19 pandemic, we painfully learned that patients with preexisting cardiovascular conditions have significantly higher mortality rates and that cardiovascular causes are essential in COVID-19 mortality,” said Stephan Baldus, MD, director of Clinic III for Internal Medicine at the Heart Center of the University Hospital Cologne in Cologne, Germany.

“A direct link between the virus and the development of acute coronary events has also been demonstrated for influenza. Studies have shown that in the early days of an influenza infection, the rates of heart attacks and subsequent deaths increase significantly,” Dr. Baldus added. “And now, this study shows that patients with cardiovascular diseases have a critically increased risk for an acute cardiovascular event during an RSV infection.”
 

RSV Surveillance

Rebecca C. Woodruff, PhD, of the Centers for Disease Control and Prevention in Atlanta, and her colleagues analyzed data from an RSV surveillance program involving hospitals in 12 US states. The data covered hospitalized adults aged 50 years and older from five RSV seasons (from 2014/2015 to 2017/2018 and 2022/2023).

The 6248 patients were hospitalized for various reasons. They had a mean age of 73 years, and 60% of them were women. RSV infection was detected through a physician-ordered test within 14 days of admission. Slightly more than half (56.4%) of the patients had a preexisting cardiovascular condition that did not necessitate hospital treatment.

The researchers reported that more than a fifth (22.4%) of the patients with RSV had an acute cardiovascular event. Acute heart failure was most common (15.8%), but there were also acute ischemic heart disease in 7.5%, hypertensive crisis in 1.3%, ventricular tachycardia in 1.1%, and cardiogenic shock in 0.6%.
 

Acute Cardiovascular Events

Among the study population, 8.5% had no documented cardiovascular preexisting conditions. However, the risk was particularly elevated in patients with cardiovascular preexisting conditions. Overall, 33.0% of them had an acute cardiovascular event during the RSV infection.

Patients with acute cardiovascular events were almost twice as likely to have a severe course as those without acute cardiovascular events. The researchers considered treatment in the intensive care unit, the need for invasive mechanical ventilation, or the patient’s death in the hospital as severe outcomes.

Of all hospitalized patients with RSV, 18.6% required intensive care unit treatment, and 4.9% died during hospitalization. Compared with those without acute cardiovascular events, those with acute cardiovascular events had a significantly higher risk for intensive care treatment (25.8% vs 16.5%) and death in the hospital (8.1% vs 4.0%).

Although the analysis is not a prospective controlled study, according to Dr. Baldus, the results strongly suggest that RSV has cardiovascular effects. “When one in five hospitalized patients develops a cardiovascular event, that’s very suggestive,” he said.
 

More Testing Needed?

The results add to the evidence that RSV infections in older patients are associated with considerable morbidity and mortality. Unlike for COVID-19 and influenza, however, there is hardly any surveillance for RSV infections. RSV testing in hospitals is rare. Many doctors opt against testing for RSV because they are not aware of the importance of RSV as a pathogen in adults, but also because the diagnosis of RSV has no therapeutic consequences, wrote Dr. Woodruff and her colleagues.

Because there is no targeted therapy for an RSV infection, the detection of RSV can only be used as a marker for a risk for the development of an acute cardiovascular event, according to Dr. Baldus. Even considering the new study data, he emphasized, “Not every patient with a cardiovascular preexisting condition needs to be tested for RSV.”

The crucial factor is the clinical presentation. “If there is a clinical indication of pulmonary impairment (shortness of breath, tachypnea, subfebrile temperatures, or a diminished general condition) it would be desirable to perform an RSV test. This is especially true for patients requiring intensive care who need respiratory support,” said Dr. Baldus.
 

Benefits of Vaccination

The results highlight the basic epidemiology of potential cardiovascular complications of RSV infections, but before RSV vaccination became available, wrote Dr. Woodruff and her colleagues.

In 2023, the first RSV vaccine for adults aged 60 years and older was approved. “Here, a door to additional possibilities opens,” said Dr. Baldus. Although there are currently no official vaccination recommendations from Germany’s Standing Vaccination Commission, medical societies of oncologists and pulmonologists recommend vaccination against RSV. “Given the relevance of cardiovascular diseases for the prognosis of patients, but also for the occurrence of an acute cardiovascular event upon detection of RSV, the corresponding recommendation is expected to come,” said Dr. Baldus.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

According to a US cross-sectional study, every fifth hospital patient with a respiratory syncytial virus (RSV) infection develops an acute cardiovascular event. For patients with a preexisting cardiovascular condition, an acute cardiovascular event occurs in every third patient, as shown by data published in JAMA Internal Medicine.

RSV attacks the respiratory tract, especially the mucous membranes of the upper airways and the ciliated epithelium of the trachea and bronchi. It is not the first respiratory virus with devastating consequences for the cardiovascular system.

“In the COVID-19 pandemic, we painfully learned that patients with preexisting cardiovascular conditions have significantly higher mortality rates and that cardiovascular causes are essential in COVID-19 mortality,” said Stephan Baldus, MD, director of Clinic III for Internal Medicine at the Heart Center of the University Hospital Cologne in Cologne, Germany.

“A direct link between the virus and the development of acute coronary events has also been demonstrated for influenza. Studies have shown that in the early days of an influenza infection, the rates of heart attacks and subsequent deaths increase significantly,” Dr. Baldus added. “And now, this study shows that patients with cardiovascular diseases have a critically increased risk for an acute cardiovascular event during an RSV infection.”
 

RSV Surveillance

Rebecca C. Woodruff, PhD, of the Centers for Disease Control and Prevention in Atlanta, and her colleagues analyzed data from an RSV surveillance program involving hospitals in 12 US states. The data covered hospitalized adults aged 50 years and older from five RSV seasons (from 2014/2015 to 2017/2018 and 2022/2023).

The 6248 patients were hospitalized for various reasons. They had a mean age of 73 years, and 60% of them were women. RSV infection was detected through a physician-ordered test within 14 days of admission. Slightly more than half (56.4%) of the patients had a preexisting cardiovascular condition that did not necessitate hospital treatment.

The researchers reported that more than a fifth (22.4%) of the patients with RSV had an acute cardiovascular event. Acute heart failure was most common (15.8%), but there were also acute ischemic heart disease in 7.5%, hypertensive crisis in 1.3%, ventricular tachycardia in 1.1%, and cardiogenic shock in 0.6%.
 

Acute Cardiovascular Events

Among the study population, 8.5% had no documented cardiovascular preexisting conditions. However, the risk was particularly elevated in patients with cardiovascular preexisting conditions. Overall, 33.0% of them had an acute cardiovascular event during the RSV infection.

Patients with acute cardiovascular events were almost twice as likely to have a severe course as those without acute cardiovascular events. The researchers considered treatment in the intensive care unit, the need for invasive mechanical ventilation, or the patient’s death in the hospital as severe outcomes.

Of all hospitalized patients with RSV, 18.6% required intensive care unit treatment, and 4.9% died during hospitalization. Compared with those without acute cardiovascular events, those with acute cardiovascular events had a significantly higher risk for intensive care treatment (25.8% vs 16.5%) and death in the hospital (8.1% vs 4.0%).

Although the analysis is not a prospective controlled study, according to Dr. Baldus, the results strongly suggest that RSV has cardiovascular effects. “When one in five hospitalized patients develops a cardiovascular event, that’s very suggestive,” he said.
 

More Testing Needed?

The results add to the evidence that RSV infections in older patients are associated with considerable morbidity and mortality. Unlike for COVID-19 and influenza, however, there is hardly any surveillance for RSV infections. RSV testing in hospitals is rare. Many doctors opt against testing for RSV because they are not aware of the importance of RSV as a pathogen in adults, but also because the diagnosis of RSV has no therapeutic consequences, wrote Dr. Woodruff and her colleagues.

Because there is no targeted therapy for an RSV infection, the detection of RSV can only be used as a marker for a risk for the development of an acute cardiovascular event, according to Dr. Baldus. Even considering the new study data, he emphasized, “Not every patient with a cardiovascular preexisting condition needs to be tested for RSV.”

The crucial factor is the clinical presentation. “If there is a clinical indication of pulmonary impairment (shortness of breath, tachypnea, subfebrile temperatures, or a diminished general condition) it would be desirable to perform an RSV test. This is especially true for patients requiring intensive care who need respiratory support,” said Dr. Baldus.
 

Benefits of Vaccination

The results highlight the basic epidemiology of potential cardiovascular complications of RSV infections, but before RSV vaccination became available, wrote Dr. Woodruff and her colleagues.

In 2023, the first RSV vaccine for adults aged 60 years and older was approved. “Here, a door to additional possibilities opens,” said Dr. Baldus. Although there are currently no official vaccination recommendations from Germany’s Standing Vaccination Commission, medical societies of oncologists and pulmonologists recommend vaccination against RSV. “Given the relevance of cardiovascular diseases for the prognosis of patients, but also for the occurrence of an acute cardiovascular event upon detection of RSV, the corresponding recommendation is expected to come,” said Dr. Baldus.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Patients with lactose intolerance are usually advised to avoid milk. However, many still consume dairy products despite experiencing gastrointestinal symptoms. Surprisingly, this "unreasonable" strategy may have the benefit of reducing the risk for type 2 diabetes, as shown in a recent American study.

“At first glance, the statement of the study seems counterintuitive,” said Robert Wagner, MD, head of the Clinical Studies Center at the German Diabetes Center-Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. “However, lactose intolerance has different manifestations.” Less severely affected individuals often consume milk and tolerate discomfort such as bloating or abdominal pain. “It is precisely these individuals that the study clearly shows have a lower incidence of diabetes associated with milk consumption,” said Dr. Wagner.
 

Milk’s Heterogeneous Effect

The effect of milk consumption on diabetes, among other factors, has been repeatedly studied in nutritional studies, with sometimes heterogeneous results in different countries. The reason for this is presumed to be that in Asia, most people — 60%-100% — are lactose intolerant, whereas in Europe, only as much as 40% of the population has lactose intolerance.

The authors, led by Kai Luo, PhD, research fellow in the Department of Epidemiology and Population Health at Albert Einstein College of Medicine in Bronx, New York, did not mention lactose tolerance and intolerance in their paper in Nature Metabolism. Instead, they divided the study population into lactase-persistent and non-lactase-persistent participants.

“Not being lactase-persistent does not necessarily exclude the ability to consume a certain amount of lactose,” said Lonneke Janssen Duijghuijsen, PhD, a nutrition scientist at Wageningen University, Wageningen, the Netherlands. “Studies have shown that many individuals who lack lactase can still consume up to 12 g of lactose per day — equivalent to the amount in a large glass of milk — without experiencing intolerance symptoms.”
 

Gut Microbiome and Metabolites

Dr. Luo and his colleagues analyzed data from 12,653 participants in the Hispanic Community Health Study/Study of Latinos, an ongoing prospective cohort study involving adults with Hispanic backgrounds. It collects detailed information on nutrition and the occurrence of diseases.

The authors examined whether the study participants were lactase-persistent or non-lactase-persistent and how frequently they consumed milk. They also analyzed the gut microbiome and various metabolites in the blood over a median follow-up period of 6 years.

The data analysis showed that higher milk consumption in non-lactase-persistent participants — but not in lactase-persistent participants — is associated with about a 30% reduced risk for type 2 diabetes when socioeconomic, demographic, and behavioral factors are accounted for. Comparable results were obtained by Dr. Luo and his colleagues with data from the UK Biobank, which served as validation.

A higher milk consumption was associated not only with a lower diabetes risk in non-lactase-persistent individuals but also with a lower body mass index. “This could be one of the factors behind the diabetes protection,” said Dr. Wagner. “However, no formal mediation analyses were conducted in the study.”

Dr. Luo’s team primarily attributed the cause of the observed association between milk consumption and diabetes risk to the gut. Increased milk intake was also associated with changes in the gut microbiome. For example, there was an enrichment of Bifidobacterium, while Prevotella decreased. Changes were also observed in the circulating metabolites in the blood, such as an increase in indole-3-propionate and a decrease in branched-chain amino acids.

These metabolites, speculated the authors, could be more intensely produced by milk-associated bacteria and might be causally related to the association between milk consumption and reduced risk for type 2 diabetes in non-lactase-persistent individuals. “The authors have not been able to provide precise evidence of these mediators, but one possible mediator of these effects could be short-chain fatty acids, which can directly or indirectly influence appetite, insulin action, or liver fat beneficially,” said Dr. Wagner.
 

Bacteria in the Colon

For Dr. Janssen Duijghuijsen, the conclusion that milk consumption can influence the composition of the microbiome and thus the metabolic profile, especially in individuals without lactase persistence, is plausible.

“Individuals with lactase persistence efficiently digest lactose and absorb the resulting galactose and glucose molecules in the small intestine. In contrast, in non-lactase-persistent individuals, lactase is not expressed in the brush border of the small intestine. As a result, lactose remains undigested in the colon and can serve as an energy source for gut bacteria. This can influence the composition of the microbiome, which in turn can alter the concentration of circulating metabolites,” she said.

Dr. Janssen Duijghuijsen has investigated the effect of lactose intake on the microbiome. In a recently published study, she also showed that increasing lactose intake by non-lactase-persistent individuals leads to changes in the microbiome, including an increase in Bifidobacteria.

“In line with the current study, we also found a significant increase in fecal beta-galactosidase activity. Given the close relationship between the composition of the gut microbiome and the metabolite profile, it is likely that changes in one can affect the other,” said Dr. Janssen Duijghuijsen.
 

Nutritional Recommendations

The nutrition scientist warned against concluding that milk consumption can protect against type 2 diabetes in non-lactase-persistent individuals, however. “The study suggests a statistical association between milk consumption, certain metabolites, and the frequency of type 2 diabetes. These associations do not provide definitive evidence of a causal relationship,” she said. Any dietary recommendations cannot be derived from the study; much more research is needed for that.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Patients with lactose intolerance are usually advised to avoid milk. However, many still consume dairy products despite experiencing gastrointestinal symptoms. Surprisingly, this "unreasonable" strategy may have the benefit of reducing the risk for type 2 diabetes, as shown in a recent American study.

“At first glance, the statement of the study seems counterintuitive,” said Robert Wagner, MD, head of the Clinical Studies Center at the German Diabetes Center-Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. “However, lactose intolerance has different manifestations.” Less severely affected individuals often consume milk and tolerate discomfort such as bloating or abdominal pain. “It is precisely these individuals that the study clearly shows have a lower incidence of diabetes associated with milk consumption,” said Dr. Wagner.
 

Milk’s Heterogeneous Effect

The effect of milk consumption on diabetes, among other factors, has been repeatedly studied in nutritional studies, with sometimes heterogeneous results in different countries. The reason for this is presumed to be that in Asia, most people — 60%-100% — are lactose intolerant, whereas in Europe, only as much as 40% of the population has lactose intolerance.

The authors, led by Kai Luo, PhD, research fellow in the Department of Epidemiology and Population Health at Albert Einstein College of Medicine in Bronx, New York, did not mention lactose tolerance and intolerance in their paper in Nature Metabolism. Instead, they divided the study population into lactase-persistent and non-lactase-persistent participants.

“Not being lactase-persistent does not necessarily exclude the ability to consume a certain amount of lactose,” said Lonneke Janssen Duijghuijsen, PhD, a nutrition scientist at Wageningen University, Wageningen, the Netherlands. “Studies have shown that many individuals who lack lactase can still consume up to 12 g of lactose per day — equivalent to the amount in a large glass of milk — without experiencing intolerance symptoms.”
 

Gut Microbiome and Metabolites

Dr. Luo and his colleagues analyzed data from 12,653 participants in the Hispanic Community Health Study/Study of Latinos, an ongoing prospective cohort study involving adults with Hispanic backgrounds. It collects detailed information on nutrition and the occurrence of diseases.

The authors examined whether the study participants were lactase-persistent or non-lactase-persistent and how frequently they consumed milk. They also analyzed the gut microbiome and various metabolites in the blood over a median follow-up period of 6 years.

The data analysis showed that higher milk consumption in non-lactase-persistent participants — but not in lactase-persistent participants — is associated with about a 30% reduced risk for type 2 diabetes when socioeconomic, demographic, and behavioral factors are accounted for. Comparable results were obtained by Dr. Luo and his colleagues with data from the UK Biobank, which served as validation.

A higher milk consumption was associated not only with a lower diabetes risk in non-lactase-persistent individuals but also with a lower body mass index. “This could be one of the factors behind the diabetes protection,” said Dr. Wagner. “However, no formal mediation analyses were conducted in the study.”

Dr. Luo’s team primarily attributed the cause of the observed association between milk consumption and diabetes risk to the gut. Increased milk intake was also associated with changes in the gut microbiome. For example, there was an enrichment of Bifidobacterium, while Prevotella decreased. Changes were also observed in the circulating metabolites in the blood, such as an increase in indole-3-propionate and a decrease in branched-chain amino acids.

These metabolites, speculated the authors, could be more intensely produced by milk-associated bacteria and might be causally related to the association between milk consumption and reduced risk for type 2 diabetes in non-lactase-persistent individuals. “The authors have not been able to provide precise evidence of these mediators, but one possible mediator of these effects could be short-chain fatty acids, which can directly or indirectly influence appetite, insulin action, or liver fat beneficially,” said Dr. Wagner.
 

Bacteria in the Colon

For Dr. Janssen Duijghuijsen, the conclusion that milk consumption can influence the composition of the microbiome and thus the metabolic profile, especially in individuals without lactase persistence, is plausible.

“Individuals with lactase persistence efficiently digest lactose and absorb the resulting galactose and glucose molecules in the small intestine. In contrast, in non-lactase-persistent individuals, lactase is not expressed in the brush border of the small intestine. As a result, lactose remains undigested in the colon and can serve as an energy source for gut bacteria. This can influence the composition of the microbiome, which in turn can alter the concentration of circulating metabolites,” she said.

Dr. Janssen Duijghuijsen has investigated the effect of lactose intake on the microbiome. In a recently published study, she also showed that increasing lactose intake by non-lactase-persistent individuals leads to changes in the microbiome, including an increase in Bifidobacteria.

“In line with the current study, we also found a significant increase in fecal beta-galactosidase activity. Given the close relationship between the composition of the gut microbiome and the metabolite profile, it is likely that changes in one can affect the other,” said Dr. Janssen Duijghuijsen.
 

Nutritional Recommendations

The nutrition scientist warned against concluding that milk consumption can protect against type 2 diabetes in non-lactase-persistent individuals, however. “The study suggests a statistical association between milk consumption, certain metabolites, and the frequency of type 2 diabetes. These associations do not provide definitive evidence of a causal relationship,” she said. Any dietary recommendations cannot be derived from the study; much more research is needed for that.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Patients with lactose intolerance are usually advised to avoid milk. However, many still consume dairy products despite experiencing gastrointestinal symptoms. Surprisingly, this "unreasonable" strategy may have the benefit of reducing the risk for type 2 diabetes, as shown in a recent American study.

“At first glance, the statement of the study seems counterintuitive,” said Robert Wagner, MD, head of the Clinical Studies Center at the German Diabetes Center-Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. “However, lactose intolerance has different manifestations.” Less severely affected individuals often consume milk and tolerate discomfort such as bloating or abdominal pain. “It is precisely these individuals that the study clearly shows have a lower incidence of diabetes associated with milk consumption,” said Dr. Wagner.
 

Milk’s Heterogeneous Effect

The effect of milk consumption on diabetes, among other factors, has been repeatedly studied in nutritional studies, with sometimes heterogeneous results in different countries. The reason for this is presumed to be that in Asia, most people — 60%-100% — are lactose intolerant, whereas in Europe, only as much as 40% of the population has lactose intolerance.

The authors, led by Kai Luo, PhD, research fellow in the Department of Epidemiology and Population Health at Albert Einstein College of Medicine in Bronx, New York, did not mention lactose tolerance and intolerance in their paper in Nature Metabolism. Instead, they divided the study population into lactase-persistent and non-lactase-persistent participants.

“Not being lactase-persistent does not necessarily exclude the ability to consume a certain amount of lactose,” said Lonneke Janssen Duijghuijsen, PhD, a nutrition scientist at Wageningen University, Wageningen, the Netherlands. “Studies have shown that many individuals who lack lactase can still consume up to 12 g of lactose per day — equivalent to the amount in a large glass of milk — without experiencing intolerance symptoms.”
 

Gut Microbiome and Metabolites

Dr. Luo and his colleagues analyzed data from 12,653 participants in the Hispanic Community Health Study/Study of Latinos, an ongoing prospective cohort study involving adults with Hispanic backgrounds. It collects detailed information on nutrition and the occurrence of diseases.

The authors examined whether the study participants were lactase-persistent or non-lactase-persistent and how frequently they consumed milk. They also analyzed the gut microbiome and various metabolites in the blood over a median follow-up period of 6 years.

The data analysis showed that higher milk consumption in non-lactase-persistent participants — but not in lactase-persistent participants — is associated with about a 30% reduced risk for type 2 diabetes when socioeconomic, demographic, and behavioral factors are accounted for. Comparable results were obtained by Dr. Luo and his colleagues with data from the UK Biobank, which served as validation.

A higher milk consumption was associated not only with a lower diabetes risk in non-lactase-persistent individuals but also with a lower body mass index. “This could be one of the factors behind the diabetes protection,” said Dr. Wagner. “However, no formal mediation analyses were conducted in the study.”

Dr. Luo’s team primarily attributed the cause of the observed association between milk consumption and diabetes risk to the gut. Increased milk intake was also associated with changes in the gut microbiome. For example, there was an enrichment of Bifidobacterium, while Prevotella decreased. Changes were also observed in the circulating metabolites in the blood, such as an increase in indole-3-propionate and a decrease in branched-chain amino acids.

These metabolites, speculated the authors, could be more intensely produced by milk-associated bacteria and might be causally related to the association between milk consumption and reduced risk for type 2 diabetes in non-lactase-persistent individuals. “The authors have not been able to provide precise evidence of these mediators, but one possible mediator of these effects could be short-chain fatty acids, which can directly or indirectly influence appetite, insulin action, or liver fat beneficially,” said Dr. Wagner.
 

Bacteria in the Colon

For Dr. Janssen Duijghuijsen, the conclusion that milk consumption can influence the composition of the microbiome and thus the metabolic profile, especially in individuals without lactase persistence, is plausible.

“Individuals with lactase persistence efficiently digest lactose and absorb the resulting galactose and glucose molecules in the small intestine. In contrast, in non-lactase-persistent individuals, lactase is not expressed in the brush border of the small intestine. As a result, lactose remains undigested in the colon and can serve as an energy source for gut bacteria. This can influence the composition of the microbiome, which in turn can alter the concentration of circulating metabolites,” she said.

Dr. Janssen Duijghuijsen has investigated the effect of lactose intake on the microbiome. In a recently published study, she also showed that increasing lactose intake by non-lactase-persistent individuals leads to changes in the microbiome, including an increase in Bifidobacteria.

“In line with the current study, we also found a significant increase in fecal beta-galactosidase activity. Given the close relationship between the composition of the gut microbiome and the metabolite profile, it is likely that changes in one can affect the other,” said Dr. Janssen Duijghuijsen.
 

Nutritional Recommendations

The nutrition scientist warned against concluding that milk consumption can protect against type 2 diabetes in non-lactase-persistent individuals, however. “The study suggests a statistical association between milk consumption, certain metabolites, and the frequency of type 2 diabetes. These associations do not provide definitive evidence of a causal relationship,” she said. Any dietary recommendations cannot be derived from the study; much more research is needed for that.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Men with advanced prostate cancer undergoing local therapies such as radiation therapy or radical prostatectomy experience significantly more gastrointestinal and sexual issues, along with problems with incontinence, in the following years, than systemically treated patients. These were the findings of a retrospective cohort study in JAMA Network Open.

The standard treatment of advanced prostate cancer is androgen deprivation therapy (ADT). “The role of local therapy has been debated for several years. Studies have shown that radiation therapy or radical prostatectomy can improve patient survival under certain conditions,” said Hubert Kübler, MD, director of the Clinic and Polyclinic for Urology and Pediatric Urology at the University Hospital Würzburg in Germany. “At academic centers, a local therapy is pursued for oligometastatic patients if they are fit enough.”

The hope is to spare patients the side effects of ADT over an extended period and thus improve their quality of life. “But what impact does local therapy itself have on the men’s quality of life, especially considering that the survival advantage gained may be relatively small?” wrote study author Saira Khan, PhD, MPH, assistant professor of surgery at Washington University School of Medicine in St. Louis, Missouri, and her colleagues.

Examining Side Effects

This question has not been thoroughly examined yet. “To our knowledge, this is one of the first studies investigating the side effects of local therapy in men with advanced prostate cancer for up to 5 years after treatment,” wrote the authors.

The cohort study included 5500 US veterans who were diagnosed with advanced prostate cancer between January 1999 and December 2013. The tumors were in stage T4 (tumor is fixed or has spread to adjacent structures), with regional lymph node metastases (N1), and partially detectable distant metastases (M1).

The average age was 68.7 years, and 31% received local therapy (eg, radiation therapy, radical prostatectomy, or both), and 69% received systemic therapy (eg, hormone therapy, chemotherapy, or both).

Types of Local Therapy

Combining radiation therapy and radical prostatectomy “diminishes the meaningfulness of the study results,” according to Dr. Kübler. “The issue should have been analyzed in much finer detail. Studies clearly show, for example, that radiation therapy consistently performs slightly worse than prostatectomy in terms of gastrointestinal complaints.”

In their paper, the researchers reported that the prevalence of side effects was high, regardless of the therapy. Overall, 916 men (75.2%) with initial local therapy and 897 men (67.1%) with initial systemic therapy reported experiencing at least one side effect lasting more than 2 years and up to 5 years.

In the first year after the initial therapy, men who underwent local therapy, compared with those who underwent systemic therapy, experienced more of the following symptoms:

• Gastrointestinal issues (odds ratio [OR], 4.08)
• Pain (OR, 1.57)
• Sexual dysfunction (OR, 2.96)
• Urinary problems, predominantly incontinence (OR, 2.25)

Lasting Side Effects

Even up to year 5 after the initial therapy, men with local therapy reported more gastrointestinal and sexual issues, as well as more frequent incontinence, than those with systemic therapy. Only the frequency of pain equalized between the two groups in the second year.

“Our results are consistent with the known side effect profile [of local therapy] in patients with clinically localized prostate cancer receiving surgery or radiation therapy instead of active surveillance,” wrote the authors.

The comparison in advanced prostate cancer, however, is not with active surveillance but with ADT. “As the study confirmed, ADT is associated with various side effects,” said Dr. Kübler. Nevertheless, it was associated with fewer side effects than local therapy in this study. The concept behind local therapy (improving prognosis while avoiding local problems) is challenging to reconcile with these results.

Contradictory Data

The results also contradict findings from other studies. Dr. Kübler pointed to the recently presented PEACE-1 study, where “local complications and issues were reduced through local therapy in high-volume and high-risk patients.”

The study did not consider subsequent interventions, such as how many patients needed transurethral manipulation in the later course of the disease to address local problems. “There are older data showing that a radical prostatectomy can reduce the need for further resections,” Dr. Kübler added.

“I find it difficult to reconcile these data with other data and with my personal experience,” said Dr. Kübler. However, he agreed with the study authors’ conclusion, emphasizing the importance of informing patients about expected side effects of local therapy in the context of potentially marginal improvements in survival.

Different Situation in Germany

“As practitioners, we sometimes underestimate the side effects we subject our patients to. We need to talk to our patients about the prognosis improvement that comes with side effects,” said Dr. Kübler. He added that a similar study in Germany might yield different results. “Dr. Khan and her colleagues examined a very specific patient population: Namely, veterans. This patient clientele often faces many social difficulties, and the treatment structure in US veterans’ care differs significantly from ours.”

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

Men with advanced prostate cancer undergoing local therapies such as radiation therapy or radical prostatectomy experience significantly more gastrointestinal and sexual issues, along with problems with incontinence, in the following years, than systemically treated patients. These were the findings of a retrospective cohort study in JAMA Network Open.

The standard treatment of advanced prostate cancer is androgen deprivation therapy (ADT). “The role of local therapy has been debated for several years. Studies have shown that radiation therapy or radical prostatectomy can improve patient survival under certain conditions,” said Hubert Kübler, MD, director of the Clinic and Polyclinic for Urology and Pediatric Urology at the University Hospital Würzburg in Germany. “At academic centers, a local therapy is pursued for oligometastatic patients if they are fit enough.”

The hope is to spare patients the side effects of ADT over an extended period and thus improve their quality of life. “But what impact does local therapy itself have on the men’s quality of life, especially considering that the survival advantage gained may be relatively small?” wrote study author Saira Khan, PhD, MPH, assistant professor of surgery at Washington University School of Medicine in St. Louis, Missouri, and her colleagues.

Examining Side Effects

This question has not been thoroughly examined yet. “To our knowledge, this is one of the first studies investigating the side effects of local therapy in men with advanced prostate cancer for up to 5 years after treatment,” wrote the authors.

The cohort study included 5500 US veterans who were diagnosed with advanced prostate cancer between January 1999 and December 2013. The tumors were in stage T4 (tumor is fixed or has spread to adjacent structures), with regional lymph node metastases (N1), and partially detectable distant metastases (M1).

The average age was 68.7 years, and 31% received local therapy (eg, radiation therapy, radical prostatectomy, or both), and 69% received systemic therapy (eg, hormone therapy, chemotherapy, or both).

Types of Local Therapy

Combining radiation therapy and radical prostatectomy “diminishes the meaningfulness of the study results,” according to Dr. Kübler. “The issue should have been analyzed in much finer detail. Studies clearly show, for example, that radiation therapy consistently performs slightly worse than prostatectomy in terms of gastrointestinal complaints.”

In their paper, the researchers reported that the prevalence of side effects was high, regardless of the therapy. Overall, 916 men (75.2%) with initial local therapy and 897 men (67.1%) with initial systemic therapy reported experiencing at least one side effect lasting more than 2 years and up to 5 years.

In the first year after the initial therapy, men who underwent local therapy, compared with those who underwent systemic therapy, experienced more of the following symptoms:

• Gastrointestinal issues (odds ratio [OR], 4.08)
• Pain (OR, 1.57)
• Sexual dysfunction (OR, 2.96)
• Urinary problems, predominantly incontinence (OR, 2.25)

Lasting Side Effects

Even up to year 5 after the initial therapy, men with local therapy reported more gastrointestinal and sexual issues, as well as more frequent incontinence, than those with systemic therapy. Only the frequency of pain equalized between the two groups in the second year.

“Our results are consistent with the known side effect profile [of local therapy] in patients with clinically localized prostate cancer receiving surgery or radiation therapy instead of active surveillance,” wrote the authors.

The comparison in advanced prostate cancer, however, is not with active surveillance but with ADT. “As the study confirmed, ADT is associated with various side effects,” said Dr. Kübler. Nevertheless, it was associated with fewer side effects than local therapy in this study. The concept behind local therapy (improving prognosis while avoiding local problems) is challenging to reconcile with these results.

Contradictory Data

The results also contradict findings from other studies. Dr. Kübler pointed to the recently presented PEACE-1 study, where “local complications and issues were reduced through local therapy in high-volume and high-risk patients.”

The study did not consider subsequent interventions, such as how many patients needed transurethral manipulation in the later course of the disease to address local problems. “There are older data showing that a radical prostatectomy can reduce the need for further resections,” Dr. Kübler added.

“I find it difficult to reconcile these data with other data and with my personal experience,” said Dr. Kübler. However, he agreed with the study authors’ conclusion, emphasizing the importance of informing patients about expected side effects of local therapy in the context of potentially marginal improvements in survival.

Different Situation in Germany

“As practitioners, we sometimes underestimate the side effects we subject our patients to. We need to talk to our patients about the prognosis improvement that comes with side effects,” said Dr. Kübler. He added that a similar study in Germany might yield different results. “Dr. Khan and her colleagues examined a very specific patient population: Namely, veterans. This patient clientele often faces many social difficulties, and the treatment structure in US veterans’ care differs significantly from ours.”

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

Men with advanced prostate cancer undergoing local therapies such as radiation therapy or radical prostatectomy experience significantly more gastrointestinal and sexual issues, along with problems with incontinence, in the following years, than systemically treated patients. These were the findings of a retrospective cohort study in JAMA Network Open.

The standard treatment of advanced prostate cancer is androgen deprivation therapy (ADT). “The role of local therapy has been debated for several years. Studies have shown that radiation therapy or radical prostatectomy can improve patient survival under certain conditions,” said Hubert Kübler, MD, director of the Clinic and Polyclinic for Urology and Pediatric Urology at the University Hospital Würzburg in Germany. “At academic centers, a local therapy is pursued for oligometastatic patients if they are fit enough.”

The hope is to spare patients the side effects of ADT over an extended period and thus improve their quality of life. “But what impact does local therapy itself have on the men’s quality of life, especially considering that the survival advantage gained may be relatively small?” wrote study author Saira Khan, PhD, MPH, assistant professor of surgery at Washington University School of Medicine in St. Louis, Missouri, and her colleagues.

Examining Side Effects

This question has not been thoroughly examined yet. “To our knowledge, this is one of the first studies investigating the side effects of local therapy in men with advanced prostate cancer for up to 5 years after treatment,” wrote the authors.

The cohort study included 5500 US veterans who were diagnosed with advanced prostate cancer between January 1999 and December 2013. The tumors were in stage T4 (tumor is fixed or has spread to adjacent structures), with regional lymph node metastases (N1), and partially detectable distant metastases (M1).

The average age was 68.7 years, and 31% received local therapy (eg, radiation therapy, radical prostatectomy, or both), and 69% received systemic therapy (eg, hormone therapy, chemotherapy, or both).

Types of Local Therapy

Combining radiation therapy and radical prostatectomy “diminishes the meaningfulness of the study results,” according to Dr. Kübler. “The issue should have been analyzed in much finer detail. Studies clearly show, for example, that radiation therapy consistently performs slightly worse than prostatectomy in terms of gastrointestinal complaints.”

In their paper, the researchers reported that the prevalence of side effects was high, regardless of the therapy. Overall, 916 men (75.2%) with initial local therapy and 897 men (67.1%) with initial systemic therapy reported experiencing at least one side effect lasting more than 2 years and up to 5 years.

In the first year after the initial therapy, men who underwent local therapy, compared with those who underwent systemic therapy, experienced more of the following symptoms:

• Gastrointestinal issues (odds ratio [OR], 4.08)
• Pain (OR, 1.57)
• Sexual dysfunction (OR, 2.96)
• Urinary problems, predominantly incontinence (OR, 2.25)

Lasting Side Effects

Even up to year 5 after the initial therapy, men with local therapy reported more gastrointestinal and sexual issues, as well as more frequent incontinence, than those with systemic therapy. Only the frequency of pain equalized between the two groups in the second year.

“Our results are consistent with the known side effect profile [of local therapy] in patients with clinically localized prostate cancer receiving surgery or radiation therapy instead of active surveillance,” wrote the authors.

The comparison in advanced prostate cancer, however, is not with active surveillance but with ADT. “As the study confirmed, ADT is associated with various side effects,” said Dr. Kübler. Nevertheless, it was associated with fewer side effects than local therapy in this study. The concept behind local therapy (improving prognosis while avoiding local problems) is challenging to reconcile with these results.

Contradictory Data

The results also contradict findings from other studies. Dr. Kübler pointed to the recently presented PEACE-1 study, where “local complications and issues were reduced through local therapy in high-volume and high-risk patients.”

The study did not consider subsequent interventions, such as how many patients needed transurethral manipulation in the later course of the disease to address local problems. “There are older data showing that a radical prostatectomy can reduce the need for further resections,” Dr. Kübler added.

“I find it difficult to reconcile these data with other data and with my personal experience,” said Dr. Kübler. However, he agreed with the study authors’ conclusion, emphasizing the importance of informing patients about expected side effects of local therapy in the context of potentially marginal improvements in survival.

Different Situation in Germany

“As practitioners, we sometimes underestimate the side effects we subject our patients to. We need to talk to our patients about the prognosis improvement that comes with side effects,” said Dr. Kübler. He added that a similar study in Germany might yield different results. “Dr. Khan and her colleagues examined a very specific patient population: Namely, veterans. This patient clientele often faces many social difficulties, and the treatment structure in US veterans’ care differs significantly from ours.”

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

A recent study sheds light on the heightened risk for burnout among physicians who take infrequent vacations and engage in patient-related work during their time off.

Conducted by the American Medical Association (AMA), the study focuses on the United States, where labor regulations regarding vacation days and compensation differ from German norms. Despite this distinction, it provides valuable insights into the vacation behavior of doctors and its potential impact on burnout risk.

Christine A. Sinsky, MD, study author and senior physician advisor for physician satisfaction at the AMA, and her colleagues invited more than 90,000 physicians to participate in a survey that used postal and computer-based methods. In all, 3024 physicians, mainly those contacted by mail, filled out the questionnaire.
 

Limited Vacation Days

A significant proportion (59.6%) of respondents reported having taken fewer than 15 vacation days in the previous year, with nearly 20% taking fewer than 5 days off. Even when officially on vacation, most (70.4%) found themselves dealing with patient-related tasks. For one-third, these tasks consumed at least 30 minutes on a typical vacation day, often longer. This phenomenon was noted especially among female physicians.

Doctors who took less vacation and worked during their time off displayed higher emotional exhaustion and reported feeling less fulfilled in their profession.
 

Administrative Tasks 

Administrative tasks, though no longer confined to paper, significantly influenced physicians’ vacation behavior. In the United States, handling messages from patients through the electronic health records (EHR) inbox demands a considerable amount of time.

Courses and tutorials on EHR inbox management are on the rise. A 2023 review linked electronic health records management to an increased burnout risk in the US medical community.
 

Lack of Coverage 

Many physicians lack coverage for their EHR inbox during their absence. Less than half (49.1%) stated that someone else manages their inbox while they are on vacation.

Difficulty in finding coverage, whether for the EHR inbox or patient care, is a leading reason why many physicians seldom take more than 3 weeks of vacation per year. Financial considerations also contribute to this decision, as revealed in the survey.
 

Vacation Lowers Risk

Further analysis showed that doctors who took more than 3 weeks of vacation per year, which is not common, had a lower risk of developing burnout. Having coverage for vacation was also associated with reduced burnout risk and increased professional fulfillment.

However, these benefits applied only when physicians truly took a break during their vacation. Respondents who spent 30 minutes or more per day on patient-related work had a higher burnout risk. The risk was 1.58 times greater for 30-60 minutes, 1.97 times greater for 60-90 minutes, and 1.92 times greater for more than 90 minutes.
 

System-Level Interventions

The vacation behavior observed in this study likely exacerbates the effects of chronic workplace overload that are associated with long working hours, thus increasing the risk for burnout, according to the researchers.

“System-level measures must be implemented to ensure physicians take an appropriate number of vacation days,” wrote the researchers. “This includes having coverage available to handle clinical activities and administrative tasks, such as managing the EHR inbox. This could potentially reduce the burnout rate among physicians.”

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

A recent study sheds light on the heightened risk for burnout among physicians who take infrequent vacations and engage in patient-related work during their time off.

Conducted by the American Medical Association (AMA), the study focuses on the United States, where labor regulations regarding vacation days and compensation differ from German norms. Despite this distinction, it provides valuable insights into the vacation behavior of doctors and its potential impact on burnout risk.

Christine A. Sinsky, MD, study author and senior physician advisor for physician satisfaction at the AMA, and her colleagues invited more than 90,000 physicians to participate in a survey that used postal and computer-based methods. In all, 3024 physicians, mainly those contacted by mail, filled out the questionnaire.
 

Limited Vacation Days

A significant proportion (59.6%) of respondents reported having taken fewer than 15 vacation days in the previous year, with nearly 20% taking fewer than 5 days off. Even when officially on vacation, most (70.4%) found themselves dealing with patient-related tasks. For one-third, these tasks consumed at least 30 minutes on a typical vacation day, often longer. This phenomenon was noted especially among female physicians.

Doctors who took less vacation and worked during their time off displayed higher emotional exhaustion and reported feeling less fulfilled in their profession.
 

Administrative Tasks 

Administrative tasks, though no longer confined to paper, significantly influenced physicians’ vacation behavior. In the United States, handling messages from patients through the electronic health records (EHR) inbox demands a considerable amount of time.

Courses and tutorials on EHR inbox management are on the rise. A 2023 review linked electronic health records management to an increased burnout risk in the US medical community.
 

Lack of Coverage 

Many physicians lack coverage for their EHR inbox during their absence. Less than half (49.1%) stated that someone else manages their inbox while they are on vacation.

Difficulty in finding coverage, whether for the EHR inbox or patient care, is a leading reason why many physicians seldom take more than 3 weeks of vacation per year. Financial considerations also contribute to this decision, as revealed in the survey.
 

Vacation Lowers Risk

Further analysis showed that doctors who took more than 3 weeks of vacation per year, which is not common, had a lower risk of developing burnout. Having coverage for vacation was also associated with reduced burnout risk and increased professional fulfillment.

However, these benefits applied only when physicians truly took a break during their vacation. Respondents who spent 30 minutes or more per day on patient-related work had a higher burnout risk. The risk was 1.58 times greater for 30-60 minutes, 1.97 times greater for 60-90 minutes, and 1.92 times greater for more than 90 minutes.
 

System-Level Interventions

The vacation behavior observed in this study likely exacerbates the effects of chronic workplace overload that are associated with long working hours, thus increasing the risk for burnout, according to the researchers.

“System-level measures must be implemented to ensure physicians take an appropriate number of vacation days,” wrote the researchers. “This includes having coverage available to handle clinical activities and administrative tasks, such as managing the EHR inbox. This could potentially reduce the burnout rate among physicians.”

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

A recent study sheds light on the heightened risk for burnout among physicians who take infrequent vacations and engage in patient-related work during their time off.

Conducted by the American Medical Association (AMA), the study focuses on the United States, where labor regulations regarding vacation days and compensation differ from German norms. Despite this distinction, it provides valuable insights into the vacation behavior of doctors and its potential impact on burnout risk.

Christine A. Sinsky, MD, study author and senior physician advisor for physician satisfaction at the AMA, and her colleagues invited more than 90,000 physicians to participate in a survey that used postal and computer-based methods. In all, 3024 physicians, mainly those contacted by mail, filled out the questionnaire.
 

Limited Vacation Days

A significant proportion (59.6%) of respondents reported having taken fewer than 15 vacation days in the previous year, with nearly 20% taking fewer than 5 days off. Even when officially on vacation, most (70.4%) found themselves dealing with patient-related tasks. For one-third, these tasks consumed at least 30 minutes on a typical vacation day, often longer. This phenomenon was noted especially among female physicians.

Doctors who took less vacation and worked during their time off displayed higher emotional exhaustion and reported feeling less fulfilled in their profession.
 

Administrative Tasks 

Administrative tasks, though no longer confined to paper, significantly influenced physicians’ vacation behavior. In the United States, handling messages from patients through the electronic health records (EHR) inbox demands a considerable amount of time.

Courses and tutorials on EHR inbox management are on the rise. A 2023 review linked electronic health records management to an increased burnout risk in the US medical community.
 

Lack of Coverage 

Many physicians lack coverage for their EHR inbox during their absence. Less than half (49.1%) stated that someone else manages their inbox while they are on vacation.

Difficulty in finding coverage, whether for the EHR inbox or patient care, is a leading reason why many physicians seldom take more than 3 weeks of vacation per year. Financial considerations also contribute to this decision, as revealed in the survey.
 

Vacation Lowers Risk

Further analysis showed that doctors who took more than 3 weeks of vacation per year, which is not common, had a lower risk of developing burnout. Having coverage for vacation was also associated with reduced burnout risk and increased professional fulfillment.

However, these benefits applied only when physicians truly took a break during their vacation. Respondents who spent 30 minutes or more per day on patient-related work had a higher burnout risk. The risk was 1.58 times greater for 30-60 minutes, 1.97 times greater for 60-90 minutes, and 1.92 times greater for more than 90 minutes.
 

System-Level Interventions

The vacation behavior observed in this study likely exacerbates the effects of chronic workplace overload that are associated with long working hours, thus increasing the risk for burnout, according to the researchers.

“System-level measures must be implemented to ensure physicians take an appropriate number of vacation days,” wrote the researchers. “This includes having coverage available to handle clinical activities and administrative tasks, such as managing the EHR inbox. This could potentially reduce the burnout rate among physicians.”

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

People who habitually add salt to their meals at the table may unknowingly be risking their kidneys, according to a study utilizing UK Biobank data. Chronic salt additions are associated with an elevated risk of developing chronic kidney disease (CKD), as revealed by researchers led by Rui Tang, a doctoral candidate in epidemiology at Tulane University in New Orleans, Louisiana. The study was published in JAMA Network Open.

Large Study Sample

In a population-based cohort study comprising over 460,000 UK Biobank participants aged 37-73 years, the researchers explored the association between adding table salt to food and increased CKD risk.

Participants indicated how often they added salt to their meals: Never or rarely, sometimes, often, or always. The follow-up period exceeded a decade, and median duration was 11.8 years. During this time, approximately 22,000 new CKD cases were documented. Data analysis revealed a significantly higher CKD risk among those who frequently added salt.

The extent of risk elevation varied with the frequency of salt additions. Even occasional salters had a 7% higher risk than those who never or rarely added salt. For frequent salters, the risk increased by 12%, and for those who always added salt, it rose to 29%. These results were adjusted for age and gender.

Worse Overall Health

The research group noted that individuals who frequently added salt were generally less healthy, adopting an unhealthier lifestyle and having lower socioeconomic status. They exhibited higher body mass index (BMI), were more likely to smoke, had diabetes or cardiovascular diseases, and had reduced estimated glomerular filtration rate (eGFR) at the beginning of the study. Moreover, their Townsend Deprivation Index, indicating material deprivation, was higher.

Considering these factors, the researchers adjusted the results not only for age and gender but also for ethnicity, Townsend Deprivation Index, eGFR, BMI, smoking status, alcohol consumption, physical activity, elevated cholesterol levels, diabetes, cardiovascular diseases, hypertension, infectious diseases, immune system disorders, and the use of nephrotoxic medications.

Association Persists

Even after accounting for these factors, a significant, albeit attenuated, association between salt additions and CKD risk remained. The risk increased by 2% for occasional salters, 5% for frequent salters, and 6% for those who always added salt.

The research group concluded that adding salt to meals could be associated with an increased risk for CKD in the general population. However, they highlighted several limitations that should be considered when interpreting the study results.

Reducing Salt 

Primarily, self-reported frequency of salt addition doesn’t precisely reflect actual salt consumption. While earlier studies validated the accuracy of this variable, the researchers acknowledged the possibility that frequent salt addition may merely be a marker for an unhealthy lifestyle.

Nevertheless, the authors speculated that reducing the frequency of salt additions to meals could contribute to lowering CKD risk in the general population. They suggested validating their results in post hoc analyses or follow-up studies from clinical trials.
 

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

People who habitually add salt to their meals at the table may unknowingly be risking their kidneys, according to a study utilizing UK Biobank data. Chronic salt additions are associated with an elevated risk of developing chronic kidney disease (CKD), as revealed by researchers led by Rui Tang, a doctoral candidate in epidemiology at Tulane University in New Orleans, Louisiana. The study was published in JAMA Network Open.

Large Study Sample

In a population-based cohort study comprising over 460,000 UK Biobank participants aged 37-73 years, the researchers explored the association between adding table salt to food and increased CKD risk.

Participants indicated how often they added salt to their meals: Never or rarely, sometimes, often, or always. The follow-up period exceeded a decade, and median duration was 11.8 years. During this time, approximately 22,000 new CKD cases were documented. Data analysis revealed a significantly higher CKD risk among those who frequently added salt.

The extent of risk elevation varied with the frequency of salt additions. Even occasional salters had a 7% higher risk than those who never or rarely added salt. For frequent salters, the risk increased by 12%, and for those who always added salt, it rose to 29%. These results were adjusted for age and gender.

Worse Overall Health

The research group noted that individuals who frequently added salt were generally less healthy, adopting an unhealthier lifestyle and having lower socioeconomic status. They exhibited higher body mass index (BMI), were more likely to smoke, had diabetes or cardiovascular diseases, and had reduced estimated glomerular filtration rate (eGFR) at the beginning of the study. Moreover, their Townsend Deprivation Index, indicating material deprivation, was higher.

Considering these factors, the researchers adjusted the results not only for age and gender but also for ethnicity, Townsend Deprivation Index, eGFR, BMI, smoking status, alcohol consumption, physical activity, elevated cholesterol levels, diabetes, cardiovascular diseases, hypertension, infectious diseases, immune system disorders, and the use of nephrotoxic medications.

Association Persists

Even after accounting for these factors, a significant, albeit attenuated, association between salt additions and CKD risk remained. The risk increased by 2% for occasional salters, 5% for frequent salters, and 6% for those who always added salt.

The research group concluded that adding salt to meals could be associated with an increased risk for CKD in the general population. However, they highlighted several limitations that should be considered when interpreting the study results.

Reducing Salt 

Primarily, self-reported frequency of salt addition doesn’t precisely reflect actual salt consumption. While earlier studies validated the accuracy of this variable, the researchers acknowledged the possibility that frequent salt addition may merely be a marker for an unhealthy lifestyle.

Nevertheless, the authors speculated that reducing the frequency of salt additions to meals could contribute to lowering CKD risk in the general population. They suggested validating their results in post hoc analyses or follow-up studies from clinical trials.
 

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

People who habitually add salt to their meals at the table may unknowingly be risking their kidneys, according to a study utilizing UK Biobank data. Chronic salt additions are associated with an elevated risk of developing chronic kidney disease (CKD), as revealed by researchers led by Rui Tang, a doctoral candidate in epidemiology at Tulane University in New Orleans, Louisiana. The study was published in JAMA Network Open.

Large Study Sample

In a population-based cohort study comprising over 460,000 UK Biobank participants aged 37-73 years, the researchers explored the association between adding table salt to food and increased CKD risk.

Participants indicated how often they added salt to their meals: Never or rarely, sometimes, often, or always. The follow-up period exceeded a decade, and median duration was 11.8 years. During this time, approximately 22,000 new CKD cases were documented. Data analysis revealed a significantly higher CKD risk among those who frequently added salt.

The extent of risk elevation varied with the frequency of salt additions. Even occasional salters had a 7% higher risk than those who never or rarely added salt. For frequent salters, the risk increased by 12%, and for those who always added salt, it rose to 29%. These results were adjusted for age and gender.

Worse Overall Health

The research group noted that individuals who frequently added salt were generally less healthy, adopting an unhealthier lifestyle and having lower socioeconomic status. They exhibited higher body mass index (BMI), were more likely to smoke, had diabetes or cardiovascular diseases, and had reduced estimated glomerular filtration rate (eGFR) at the beginning of the study. Moreover, their Townsend Deprivation Index, indicating material deprivation, was higher.

Considering these factors, the researchers adjusted the results not only for age and gender but also for ethnicity, Townsend Deprivation Index, eGFR, BMI, smoking status, alcohol consumption, physical activity, elevated cholesterol levels, diabetes, cardiovascular diseases, hypertension, infectious diseases, immune system disorders, and the use of nephrotoxic medications.

Association Persists

Even after accounting for these factors, a significant, albeit attenuated, association between salt additions and CKD risk remained. The risk increased by 2% for occasional salters, 5% for frequent salters, and 6% for those who always added salt.

The research group concluded that adding salt to meals could be associated with an increased risk for CKD in the general population. However, they highlighted several limitations that should be considered when interpreting the study results.

Reducing Salt 

Primarily, self-reported frequency of salt addition doesn’t precisely reflect actual salt consumption. While earlier studies validated the accuracy of this variable, the researchers acknowledged the possibility that frequent salt addition may merely be a marker for an unhealthy lifestyle.

Nevertheless, the authors speculated that reducing the frequency of salt additions to meals could contribute to lowering CKD risk in the general population. They suggested validating their results in post hoc analyses or follow-up studies from clinical trials.
 

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

The approval of the GLP-1 receptor agonist semaglutide for weight regulation in January 2023 ushered in a new era of obesity therapy. In recent months, however, drug regulatory authorities have also documented rare, occasionally severe side effects associated with the use of these agents in diabetes therapy that doctors may not necessarily have been aware of.

“When millions of people are treated with medications like semaglutide, even relatively rare side effects occur in a large number of individuals,” Susan Yanovski, MD, codirector of the Office of Obesity Research at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, said in a JAMA news report.

Despite the low incidence of these adverse events and the likelihood that the benefits outweigh these risks in individuals with severe obesity, doctors and patients should be aware of these serious side effects, she added.

GLP-1 receptor agonists like semaglutide or liraglutide mimic certain intestinal hormones. Almost all their characteristic side effects involve the gastrointestinal tract: nausea, vomiting, constipation, and diarrhea. However, these are not the rare, severe side effects that are gaining increasing attention.
 

Severe Gastric Problems

A recent analysis published in JAMA shows that GLP-1 receptor agonists are associated with a ninefold higher risk of pancreatitis, compared with bupropion, an older weight-loss medication. Patients receiving GLP-1 receptor agonists also had four times more frequent intestinal obstruction and more than three times more frequent gastroparesis. The absolute risks for these complications, however, were less than 1% per year of use.

There were no indications of an increased risk for gallbladder diseases. Acute pancreatitis and acute gallbladder diseases are known complications of GLP-1 receptor agonists.

These results “reinforce that these are effective medications, and all medications have side effects,” said Dr. Yanovski. She emphasized that despite a significant increase in relative risk, however, the absolute risk remains very low.
 

Anesthetic Complications

In the spring of 2023, reports of patients taking GLP-1 receptor agonists and vomiting or aspirating food during anesthesia surfaced in some scientific journals. It was particularly noticeable that some of these patients vomited unusually large amounts of stomach contents, even though they had not eaten anything, as directed by the doctor before the operation.

Experts believe that the slowed gastric emptying intentionally caused by GLP-1 receptor agonists could be responsible for these problems.

The American Society of Anesthesiologists now recommends that patients do not take GLP-1 receptor agonists on the day of surgery and discontinue weekly administered agents like Wegovy 7 days before the procedure.

Increased Suicidality Risk?

In July, case reports of depression and suicidal ideation led the European Medicines Agency to investigate about 150 cases of potential self-harm and suicidal thoughts in patients who had received liraglutide or semaglutide. The review now also includes other GLP-1 receptor agonists. Results of the review process are expected in December.

Dr. Yanovski noted that it is unclear whether these incidents are caused by the drugs, but suicidal thoughts and suicidal behavior have also been observed with other medications for obesity treatment (eg, rimonabant). “It is certainly a good idea to use these medications cautiously in patients with a history of suicidality and monitor the patients accordingly,” she said.
 

Long-Term Safety

GLP-1 receptor agonists likely need to be used long term, potentially for life, for the effects on body weight to persist. Whether there are side effects and complications that only become apparent over time is currently unknown — especially when these medications are used for weight reduction.

Studies in rodents have suggested an increased risk of medullary thyroid carcinomas. Whether a similar signal exists in humans may only become apparent in many years. In patients who have had medullary thyroid carcinoma themselves or in the family, dulaglutide, liraglutide, semaglutide, and tirzepatide, a dual GLP-1/GIP receptor agonist, are contraindicated.

With dual agonists like tirzepatide or even triple agonists like retatrutide (GLP-1/GIP/glucagon), patients can lose significantly more weight than with the monoagonist semaglutide. Gastrointestinal events were also frequent in studies of dual agonists.
 

Awaiting Guideline Updates

Guidelines for using these new medications are still scarce. “There are clinical guidelines for obesity therapy, but they were all written before the GLP-1 receptor agonists came on the market,” said Dr. Yanovski. “Medical societies are currently working intensively to develop new guidelines to help doctors use these medications safely and effectively in clinical practice.”
 

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

The approval of the GLP-1 receptor agonist semaglutide for weight regulation in January 2023 ushered in a new era of obesity therapy. In recent months, however, drug regulatory authorities have also documented rare, occasionally severe side effects associated with the use of these agents in diabetes therapy that doctors may not necessarily have been aware of.

“When millions of people are treated with medications like semaglutide, even relatively rare side effects occur in a large number of individuals,” Susan Yanovski, MD, codirector of the Office of Obesity Research at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, said in a JAMA news report.

Despite the low incidence of these adverse events and the likelihood that the benefits outweigh these risks in individuals with severe obesity, doctors and patients should be aware of these serious side effects, she added.

GLP-1 receptor agonists like semaglutide or liraglutide mimic certain intestinal hormones. Almost all their characteristic side effects involve the gastrointestinal tract: nausea, vomiting, constipation, and diarrhea. However, these are not the rare, severe side effects that are gaining increasing attention.
 

Severe Gastric Problems

A recent analysis published in JAMA shows that GLP-1 receptor agonists are associated with a ninefold higher risk of pancreatitis, compared with bupropion, an older weight-loss medication. Patients receiving GLP-1 receptor agonists also had four times more frequent intestinal obstruction and more than three times more frequent gastroparesis. The absolute risks for these complications, however, were less than 1% per year of use.

There were no indications of an increased risk for gallbladder diseases. Acute pancreatitis and acute gallbladder diseases are known complications of GLP-1 receptor agonists.

These results “reinforce that these are effective medications, and all medications have side effects,” said Dr. Yanovski. She emphasized that despite a significant increase in relative risk, however, the absolute risk remains very low.
 

Anesthetic Complications

In the spring of 2023, reports of patients taking GLP-1 receptor agonists and vomiting or aspirating food during anesthesia surfaced in some scientific journals. It was particularly noticeable that some of these patients vomited unusually large amounts of stomach contents, even though they had not eaten anything, as directed by the doctor before the operation.

Experts believe that the slowed gastric emptying intentionally caused by GLP-1 receptor agonists could be responsible for these problems.

The American Society of Anesthesiologists now recommends that patients do not take GLP-1 receptor agonists on the day of surgery and discontinue weekly administered agents like Wegovy 7 days before the procedure.

Increased Suicidality Risk?

In July, case reports of depression and suicidal ideation led the European Medicines Agency to investigate about 150 cases of potential self-harm and suicidal thoughts in patients who had received liraglutide or semaglutide. The review now also includes other GLP-1 receptor agonists. Results of the review process are expected in December.

Dr. Yanovski noted that it is unclear whether these incidents are caused by the drugs, but suicidal thoughts and suicidal behavior have also been observed with other medications for obesity treatment (eg, rimonabant). “It is certainly a good idea to use these medications cautiously in patients with a history of suicidality and monitor the patients accordingly,” she said.
 

Long-Term Safety

GLP-1 receptor agonists likely need to be used long term, potentially for life, for the effects on body weight to persist. Whether there are side effects and complications that only become apparent over time is currently unknown — especially when these medications are used for weight reduction.

Studies in rodents have suggested an increased risk of medullary thyroid carcinomas. Whether a similar signal exists in humans may only become apparent in many years. In patients who have had medullary thyroid carcinoma themselves or in the family, dulaglutide, liraglutide, semaglutide, and tirzepatide, a dual GLP-1/GIP receptor agonist, are contraindicated.

With dual agonists like tirzepatide or even triple agonists like retatrutide (GLP-1/GIP/glucagon), patients can lose significantly more weight than with the monoagonist semaglutide. Gastrointestinal events were also frequent in studies of dual agonists.
 

Awaiting Guideline Updates

Guidelines for using these new medications are still scarce. “There are clinical guidelines for obesity therapy, but they were all written before the GLP-1 receptor agonists came on the market,” said Dr. Yanovski. “Medical societies are currently working intensively to develop new guidelines to help doctors use these medications safely and effectively in clinical practice.”
 

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

The approval of the GLP-1 receptor agonist semaglutide for weight regulation in January 2023 ushered in a new era of obesity therapy. In recent months, however, drug regulatory authorities have also documented rare, occasionally severe side effects associated with the use of these agents in diabetes therapy that doctors may not necessarily have been aware of.

“When millions of people are treated with medications like semaglutide, even relatively rare side effects occur in a large number of individuals,” Susan Yanovski, MD, codirector of the Office of Obesity Research at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, said in a JAMA news report.

Despite the low incidence of these adverse events and the likelihood that the benefits outweigh these risks in individuals with severe obesity, doctors and patients should be aware of these serious side effects, she added.

GLP-1 receptor agonists like semaglutide or liraglutide mimic certain intestinal hormones. Almost all their characteristic side effects involve the gastrointestinal tract: nausea, vomiting, constipation, and diarrhea. However, these are not the rare, severe side effects that are gaining increasing attention.
 

Severe Gastric Problems

A recent analysis published in JAMA shows that GLP-1 receptor agonists are associated with a ninefold higher risk of pancreatitis, compared with bupropion, an older weight-loss medication. Patients receiving GLP-1 receptor agonists also had four times more frequent intestinal obstruction and more than three times more frequent gastroparesis. The absolute risks for these complications, however, were less than 1% per year of use.

There were no indications of an increased risk for gallbladder diseases. Acute pancreatitis and acute gallbladder diseases are known complications of GLP-1 receptor agonists.

These results “reinforce that these are effective medications, and all medications have side effects,” said Dr. Yanovski. She emphasized that despite a significant increase in relative risk, however, the absolute risk remains very low.
 

Anesthetic Complications

In the spring of 2023, reports of patients taking GLP-1 receptor agonists and vomiting or aspirating food during anesthesia surfaced in some scientific journals. It was particularly noticeable that some of these patients vomited unusually large amounts of stomach contents, even though they had not eaten anything, as directed by the doctor before the operation.

Experts believe that the slowed gastric emptying intentionally caused by GLP-1 receptor agonists could be responsible for these problems.

The American Society of Anesthesiologists now recommends that patients do not take GLP-1 receptor agonists on the day of surgery and discontinue weekly administered agents like Wegovy 7 days before the procedure.

Increased Suicidality Risk?

In July, case reports of depression and suicidal ideation led the European Medicines Agency to investigate about 150 cases of potential self-harm and suicidal thoughts in patients who had received liraglutide or semaglutide. The review now also includes other GLP-1 receptor agonists. Results of the review process are expected in December.

Dr. Yanovski noted that it is unclear whether these incidents are caused by the drugs, but suicidal thoughts and suicidal behavior have also been observed with other medications for obesity treatment (eg, rimonabant). “It is certainly a good idea to use these medications cautiously in patients with a history of suicidality and monitor the patients accordingly,” she said.
 

Long-Term Safety

GLP-1 receptor agonists likely need to be used long term, potentially for life, for the effects on body weight to persist. Whether there are side effects and complications that only become apparent over time is currently unknown — especially when these medications are used for weight reduction.

Studies in rodents have suggested an increased risk of medullary thyroid carcinomas. Whether a similar signal exists in humans may only become apparent in many years. In patients who have had medullary thyroid carcinoma themselves or in the family, dulaglutide, liraglutide, semaglutide, and tirzepatide, a dual GLP-1/GIP receptor agonist, are contraindicated.

With dual agonists like tirzepatide or even triple agonists like retatrutide (GLP-1/GIP/glucagon), patients can lose significantly more weight than with the monoagonist semaglutide. Gastrointestinal events were also frequent in studies of dual agonists.
 

Awaiting Guideline Updates

Guidelines for using these new medications are still scarce. “There are clinical guidelines for obesity therapy, but they were all written before the GLP-1 receptor agonists came on the market,” said Dr. Yanovski. “Medical societies are currently working intensively to develop new guidelines to help doctors use these medications safely and effectively in clinical practice.”
 

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

Even at an advanced age, superagers have the memory of someone 20 or 30 years their junior. But why is that? A new study shows that, in superagers, age-related atrophy of the gray matter, especially in the areas responsible for memory, develops much more slowly than in normal older adults. However, the study also emphasizes the importance of physical and mental fitness for a healthy aging process.

“One of the most important unanswered questions with regard to superagers is: ‘Are they resistant to age-related memory loss, or do they have coping mechanisms that allow them to better offset this memory loss?’ ” wrote Marta Garo-Pascual, a PhD candidate at the Autonomous University of Madrid, Spain, and colleagues in the Lancet Healthy Longevity. “Our results indicate that superagers are resistant to these processes.”
 

Six years’ monitoring

From a cohort of older adults who had participated in a study aiming to identify early indicators of Alzheimer’s disease, the research group chose 64 superagers and 55 normal senior citizens. The latter served as the control group. While the superagers performed just as well in a memory test as people 30 years their junior, the control group’s performance was in line with their age and level of education.

All study participants were over age 79 years. Both the group of superagers and the control group included more females than males. On average, they were monitored for 6 years. During this period, a checkup was scheduled annually with an MRI examination, clinical tests, blood tests, and documentation of lifestyle factors.

For Alessandro Cellerino, PhD, of the Leibniz Institute on Aging–Fritz Lipmann Institute in Jena, Germany, this is the most crucial aspect of the study. “Even before this study, we knew that superagers demonstrated less atrophy in certain areas of the brain, but this was always only ever based on a single measurement.”
 

Memory centers protected

The MRI examinations confirmed that in superagers, gray matter atrophy in the regions responsible for memory (such as the medial temporal lobe and cholinergic forebrain), as well in regions important for movement (such as the motor thalamus), was less pronounced. In addition, the volume of gray matter in these regions, especially in the medial temporal lobe, decreased much more slowly in the superagers than in the control subjects over the study period.

Ms. Garo-Pascual and associates used a machine-learning algorithm to differentiate between superagers and normal older adults. From the 89 demographic, lifestyle, and clinical factors entered into the algorithm, two were the most important for the classification: the ability to move and mental health.
 

Mobility and mental health

Clinical tests such as the Timed Up-and-Go Test and the Finger Tapping Test revealed that superagers can be distinguished from the normally aging control subjects with regard to their mobility and fine motor skills. Their physical condition was better, although they, by their own admission, did not move any more than the control subjects in day-to-day life. According to Dr. Cellerino, this finding confirms that physical activity is paramount for cognitive function. “These people were over 80 years old – the fact that there was not much difference between their levels of activity is not surprising. Much more relevant is the question of how you get there – i.e., how active you are at the ages of 40, 50 or even 60 years old.”

Remaining active is important

As a matter of fact, the superagers indicated that generally they had been more active than the control subjects during their middle years. “Attempting to stay physically fit is essential; even if it just means going for a walk or taking the stairs,” said Dr. Cellerino.

On average, the superagers also fared much better in tests on physical health than the control subjects. They suffered significantly less from depression or anxiety disorders. “Earlier studies suggest that depression and anxiety disorders may influence performance in memory tests across all ages and that they are risk factors for developing dementia,” said Dr. Cellerino.

To avoid mental health issues in later life, gerontologist Dr. Cellerino recommended remaining socially engaged and involved. “Depression and anxiety are commonly also a consequence of social isolation,” he said.
 

Potential genetic differences

Blood sample analyses demonstrated that the superagers exhibited lower concentrations of biomarkers for neurodegenerative diseases than the control group did. In contrast, there was no difference between the two groups in the prevalence of the apo e4 allele, one of the most important genetic risk factors for Alzheimer’s disease. Nevertheless, Ms. Garo-Pascual and associates assume that genetics also play a role. They found that, despite 89 variables employed, the algorithm used could only distinguish superagers from normal older adults 66% of the time. This suggests that additional factors must be in play, such as genetic differences.

Body and mind

Since this is an observational study, whether the determined factors have a direct effect on superaging cannot be ascertained, the authors wrote. However, the results are consistent with earlier findings.

“Regarding the management of old age, we actually haven’t learned anything more than what we already knew. But it does confirm that physical and mental function are closely entwined and that we must maintain both to age healthily,” Dr. Cellerino concluded.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

Even at an advanced age, superagers have the memory of someone 20 or 30 years their junior. But why is that? A new study shows that, in superagers, age-related atrophy of the gray matter, especially in the areas responsible for memory, develops much more slowly than in normal older adults. However, the study also emphasizes the importance of physical and mental fitness for a healthy aging process.

“One of the most important unanswered questions with regard to superagers is: ‘Are they resistant to age-related memory loss, or do they have coping mechanisms that allow them to better offset this memory loss?’ ” wrote Marta Garo-Pascual, a PhD candidate at the Autonomous University of Madrid, Spain, and colleagues in the Lancet Healthy Longevity. “Our results indicate that superagers are resistant to these processes.”
 

Six years’ monitoring

From a cohort of older adults who had participated in a study aiming to identify early indicators of Alzheimer’s disease, the research group chose 64 superagers and 55 normal senior citizens. The latter served as the control group. While the superagers performed just as well in a memory test as people 30 years their junior, the control group’s performance was in line with their age and level of education.

All study participants were over age 79 years. Both the group of superagers and the control group included more females than males. On average, they were monitored for 6 years. During this period, a checkup was scheduled annually with an MRI examination, clinical tests, blood tests, and documentation of lifestyle factors.

For Alessandro Cellerino, PhD, of the Leibniz Institute on Aging–Fritz Lipmann Institute in Jena, Germany, this is the most crucial aspect of the study. “Even before this study, we knew that superagers demonstrated less atrophy in certain areas of the brain, but this was always only ever based on a single measurement.”
 

Memory centers protected

The MRI examinations confirmed that in superagers, gray matter atrophy in the regions responsible for memory (such as the medial temporal lobe and cholinergic forebrain), as well in regions important for movement (such as the motor thalamus), was less pronounced. In addition, the volume of gray matter in these regions, especially in the medial temporal lobe, decreased much more slowly in the superagers than in the control subjects over the study period.

Ms. Garo-Pascual and associates used a machine-learning algorithm to differentiate between superagers and normal older adults. From the 89 demographic, lifestyle, and clinical factors entered into the algorithm, two were the most important for the classification: the ability to move and mental health.
 

Mobility and mental health

Clinical tests such as the Timed Up-and-Go Test and the Finger Tapping Test revealed that superagers can be distinguished from the normally aging control subjects with regard to their mobility and fine motor skills. Their physical condition was better, although they, by their own admission, did not move any more than the control subjects in day-to-day life. According to Dr. Cellerino, this finding confirms that physical activity is paramount for cognitive function. “These people were over 80 years old – the fact that there was not much difference between their levels of activity is not surprising. Much more relevant is the question of how you get there – i.e., how active you are at the ages of 40, 50 or even 60 years old.”

Remaining active is important

As a matter of fact, the superagers indicated that generally they had been more active than the control subjects during their middle years. “Attempting to stay physically fit is essential; even if it just means going for a walk or taking the stairs,” said Dr. Cellerino.

On average, the superagers also fared much better in tests on physical health than the control subjects. They suffered significantly less from depression or anxiety disorders. “Earlier studies suggest that depression and anxiety disorders may influence performance in memory tests across all ages and that they are risk factors for developing dementia,” said Dr. Cellerino.

To avoid mental health issues in later life, gerontologist Dr. Cellerino recommended remaining socially engaged and involved. “Depression and anxiety are commonly also a consequence of social isolation,” he said.
 

Potential genetic differences

Blood sample analyses demonstrated that the superagers exhibited lower concentrations of biomarkers for neurodegenerative diseases than the control group did. In contrast, there was no difference between the two groups in the prevalence of the apo e4 allele, one of the most important genetic risk factors for Alzheimer’s disease. Nevertheless, Ms. Garo-Pascual and associates assume that genetics also play a role. They found that, despite 89 variables employed, the algorithm used could only distinguish superagers from normal older adults 66% of the time. This suggests that additional factors must be in play, such as genetic differences.

Body and mind

Since this is an observational study, whether the determined factors have a direct effect on superaging cannot be ascertained, the authors wrote. However, the results are consistent with earlier findings.

“Regarding the management of old age, we actually haven’t learned anything more than what we already knew. But it does confirm that physical and mental function are closely entwined and that we must maintain both to age healthily,” Dr. Cellerino concluded.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

Even at an advanced age, superagers have the memory of someone 20 or 30 years their junior. But why is that? A new study shows that, in superagers, age-related atrophy of the gray matter, especially in the areas responsible for memory, develops much more slowly than in normal older adults. However, the study also emphasizes the importance of physical and mental fitness for a healthy aging process.

“One of the most important unanswered questions with regard to superagers is: ‘Are they resistant to age-related memory loss, or do they have coping mechanisms that allow them to better offset this memory loss?’ ” wrote Marta Garo-Pascual, a PhD candidate at the Autonomous University of Madrid, Spain, and colleagues in the Lancet Healthy Longevity. “Our results indicate that superagers are resistant to these processes.”
 

Six years’ monitoring

From a cohort of older adults who had participated in a study aiming to identify early indicators of Alzheimer’s disease, the research group chose 64 superagers and 55 normal senior citizens. The latter served as the control group. While the superagers performed just as well in a memory test as people 30 years their junior, the control group’s performance was in line with their age and level of education.

All study participants were over age 79 years. Both the group of superagers and the control group included more females than males. On average, they were monitored for 6 years. During this period, a checkup was scheduled annually with an MRI examination, clinical tests, blood tests, and documentation of lifestyle factors.

For Alessandro Cellerino, PhD, of the Leibniz Institute on Aging–Fritz Lipmann Institute in Jena, Germany, this is the most crucial aspect of the study. “Even before this study, we knew that superagers demonstrated less atrophy in certain areas of the brain, but this was always only ever based on a single measurement.”
 

Memory centers protected

The MRI examinations confirmed that in superagers, gray matter atrophy in the regions responsible for memory (such as the medial temporal lobe and cholinergic forebrain), as well in regions important for movement (such as the motor thalamus), was less pronounced. In addition, the volume of gray matter in these regions, especially in the medial temporal lobe, decreased much more slowly in the superagers than in the control subjects over the study period.

Ms. Garo-Pascual and associates used a machine-learning algorithm to differentiate between superagers and normal older adults. From the 89 demographic, lifestyle, and clinical factors entered into the algorithm, two were the most important for the classification: the ability to move and mental health.
 

Mobility and mental health

Clinical tests such as the Timed Up-and-Go Test and the Finger Tapping Test revealed that superagers can be distinguished from the normally aging control subjects with regard to their mobility and fine motor skills. Their physical condition was better, although they, by their own admission, did not move any more than the control subjects in day-to-day life. According to Dr. Cellerino, this finding confirms that physical activity is paramount for cognitive function. “These people were over 80 years old – the fact that there was not much difference between their levels of activity is not surprising. Much more relevant is the question of how you get there – i.e., how active you are at the ages of 40, 50 or even 60 years old.”

Remaining active is important

As a matter of fact, the superagers indicated that generally they had been more active than the control subjects during their middle years. “Attempting to stay physically fit is essential; even if it just means going for a walk or taking the stairs,” said Dr. Cellerino.

On average, the superagers also fared much better in tests on physical health than the control subjects. They suffered significantly less from depression or anxiety disorders. “Earlier studies suggest that depression and anxiety disorders may influence performance in memory tests across all ages and that they are risk factors for developing dementia,” said Dr. Cellerino.

To avoid mental health issues in later life, gerontologist Dr. Cellerino recommended remaining socially engaged and involved. “Depression and anxiety are commonly also a consequence of social isolation,” he said.
 

Potential genetic differences

Blood sample analyses demonstrated that the superagers exhibited lower concentrations of biomarkers for neurodegenerative diseases than the control group did. In contrast, there was no difference between the two groups in the prevalence of the apo e4 allele, one of the most important genetic risk factors for Alzheimer’s disease. Nevertheless, Ms. Garo-Pascual and associates assume that genetics also play a role. They found that, despite 89 variables employed, the algorithm used could only distinguish superagers from normal older adults 66% of the time. This suggests that additional factors must be in play, such as genetic differences.

Body and mind

Since this is an observational study, whether the determined factors have a direct effect on superaging cannot be ascertained, the authors wrote. However, the results are consistent with earlier findings.

“Regarding the management of old age, we actually haven’t learned anything more than what we already knew. But it does confirm that physical and mental function are closely entwined and that we must maintain both to age healthily,” Dr. Cellerino concluded.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

Sudden cardiac arrest is the term given to death that results from a cardiac cause and occurs within an hour of symptoms being observed. If no witnesses are present, sudden cardiac arrest is present if the person had been in apparently good health 24 hours before cardiac death. Fatality is usually a result of sustained ventricular fibrillation or sustained ventricular tachycardia that leads to cardiac arrest.

What should primary care practitioners consider in order to detect at-risk patients in time?
 

Recognizing warning signs

Warning signs that should prompt physicians to consider an increased risk of sudden cardiac arrest include the following:

• Unexplained, brief fainting episodes that above all occur with stress, physical activity, or loud noises (for example, alarm ringing)
• Seizures without a clear pathologic EEG result (for example, epilepsy)
• Unexplained accidents or car crashes
• Heart failure or pacemaker dependency before age 50 years

“These are all indications that could point to an underlying heart disease that should be investigated by a medical professional,” explained Silke Kauferstein, PhD, head of the Center for Sudden Cardiac Arrest and Familial Arrhythmia Syndrome at the Institute of Forensic Medicine of the University Frankfurt am Main (Germany), in a podcast by the German Heart Foundation.
 

Sports rarely responsible

Sudden cardiac arrest has numerous causes. Sudden cardiac arrests in a professional sports environment always attract attention. Yet sports play a less important role in sudden cardiac arrest than is often assumed, even in young individuals.

“The incidence of sudden cardiac arrest is on average 0.7-3 per 100,000 sports players from all age groups,” said Thomas Voigtländer, MD, chair of the German Heart Foundation, in an interview. Men make up 95% of those affected, and 90% of these events occur during recreational sports.
 

Inherited disorders

The most significant risk factor for sudden cardiac arrest is age; it is often associated with coronary heart disease. This factor can be significant from as early as age 35 years. Among young individuals, sudden cardiac arrest is often a result of congenital heart diseases, such as hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. Diseases such as long QT syndrome and Brugada syndrome can also lead to sudden cardiac arrest.

Among young sports players who experience sudden cardiac arrest, the cause is often an overlooked hereditary factor. “Cardiac screening is recommended in particular for young, high-performance athletes from around 14 years old,” said Dr. Voigtländer, who is also a cardiologist and medical director of the Agaplesion Bethanien Hospital in Frankfurt.
 

Testing of family

“If sudden cardiac arrest or an unexplained sudden death occurs at a young age in the family, the primary care practitioner must be aware that this could be due to heart diseases that could affect the rest of the family,” said Dr. Voigtländer.

In these cases, primary care practitioners must connect the other family members to specialist outpatient departments that can test for genetic factors, he added. “Many of these genetic diseases can be treated successfully if they are diagnosed promptly.”
 

Lack of knowledge

Dr. Kauferstein, who runs such a specialist outpatient department, said, “unfortunately, many affected families do not know that they should be tested as well. This lack of knowledge can also lead to fatal consequences for relatives.”

For this reason, she believes that it is crucial to provide more information to the general population. Sudden cardiac arrest is often the first sign of an underlying heart disease in young, healthy individuals. “We do see warning signals in our in-depth testing of sudden cardiac arrest cases that have often been overlooked,” said Dr. Kauferstein.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

Sudden cardiac arrest is the term given to death that results from a cardiac cause and occurs within an hour of symptoms being observed. If no witnesses are present, sudden cardiac arrest is present if the person had been in apparently good health 24 hours before cardiac death. Fatality is usually a result of sustained ventricular fibrillation or sustained ventricular tachycardia that leads to cardiac arrest.

What should primary care practitioners consider in order to detect at-risk patients in time?
 

Recognizing warning signs

Warning signs that should prompt physicians to consider an increased risk of sudden cardiac arrest include the following:

• Unexplained, brief fainting episodes that above all occur with stress, physical activity, or loud noises (for example, alarm ringing)
• Seizures without a clear pathologic EEG result (for example, epilepsy)
• Unexplained accidents or car crashes
• Heart failure or pacemaker dependency before age 50 years

“These are all indications that could point to an underlying heart disease that should be investigated by a medical professional,” explained Silke Kauferstein, PhD, head of the Center for Sudden Cardiac Arrest and Familial Arrhythmia Syndrome at the Institute of Forensic Medicine of the University Frankfurt am Main (Germany), in a podcast by the German Heart Foundation.
 

Sports rarely responsible

Sudden cardiac arrest has numerous causes. Sudden cardiac arrests in a professional sports environment always attract attention. Yet sports play a less important role in sudden cardiac arrest than is often assumed, even in young individuals.

“The incidence of sudden cardiac arrest is on average 0.7-3 per 100,000 sports players from all age groups,” said Thomas Voigtländer, MD, chair of the German Heart Foundation, in an interview. Men make up 95% of those affected, and 90% of these events occur during recreational sports.
 

Inherited disorders

The most significant risk factor for sudden cardiac arrest is age; it is often associated with coronary heart disease. This factor can be significant from as early as age 35 years. Among young individuals, sudden cardiac arrest is often a result of congenital heart diseases, such as hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. Diseases such as long QT syndrome and Brugada syndrome can also lead to sudden cardiac arrest.

Among young sports players who experience sudden cardiac arrest, the cause is often an overlooked hereditary factor. “Cardiac screening is recommended in particular for young, high-performance athletes from around 14 years old,” said Dr. Voigtländer, who is also a cardiologist and medical director of the Agaplesion Bethanien Hospital in Frankfurt.
 

Testing of family

“If sudden cardiac arrest or an unexplained sudden death occurs at a young age in the family, the primary care practitioner must be aware that this could be due to heart diseases that could affect the rest of the family,” said Dr. Voigtländer.

In these cases, primary care practitioners must connect the other family members to specialist outpatient departments that can test for genetic factors, he added. “Many of these genetic diseases can be treated successfully if they are diagnosed promptly.”
 

Lack of knowledge

Dr. Kauferstein, who runs such a specialist outpatient department, said, “unfortunately, many affected families do not know that they should be tested as well. This lack of knowledge can also lead to fatal consequences for relatives.”

For this reason, she believes that it is crucial to provide more information to the general population. Sudden cardiac arrest is often the first sign of an underlying heart disease in young, healthy individuals. “We do see warning signals in our in-depth testing of sudden cardiac arrest cases that have often been overlooked,” said Dr. Kauferstein.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

Sudden cardiac arrest is the term given to death that results from a cardiac cause and occurs within an hour of symptoms being observed. If no witnesses are present, sudden cardiac arrest is present if the person had been in apparently good health 24 hours before cardiac death. Fatality is usually a result of sustained ventricular fibrillation or sustained ventricular tachycardia that leads to cardiac arrest.

What should primary care practitioners consider in order to detect at-risk patients in time?
 

Recognizing warning signs

Warning signs that should prompt physicians to consider an increased risk of sudden cardiac arrest include the following:

• Unexplained, brief fainting episodes that above all occur with stress, physical activity, or loud noises (for example, alarm ringing)
• Seizures without a clear pathologic EEG result (for example, epilepsy)
• Unexplained accidents or car crashes
• Heart failure or pacemaker dependency before age 50 years

“These are all indications that could point to an underlying heart disease that should be investigated by a medical professional,” explained Silke Kauferstein, PhD, head of the Center for Sudden Cardiac Arrest and Familial Arrhythmia Syndrome at the Institute of Forensic Medicine of the University Frankfurt am Main (Germany), in a podcast by the German Heart Foundation.
 

Sports rarely responsible

Sudden cardiac arrest has numerous causes. Sudden cardiac arrests in a professional sports environment always attract attention. Yet sports play a less important role in sudden cardiac arrest than is often assumed, even in young individuals.

“The incidence of sudden cardiac arrest is on average 0.7-3 per 100,000 sports players from all age groups,” said Thomas Voigtländer, MD, chair of the German Heart Foundation, in an interview. Men make up 95% of those affected, and 90% of these events occur during recreational sports.
 

Inherited disorders

The most significant risk factor for sudden cardiac arrest is age; it is often associated with coronary heart disease. This factor can be significant from as early as age 35 years. Among young individuals, sudden cardiac arrest is often a result of congenital heart diseases, such as hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. Diseases such as long QT syndrome and Brugada syndrome can also lead to sudden cardiac arrest.

Among young sports players who experience sudden cardiac arrest, the cause is often an overlooked hereditary factor. “Cardiac screening is recommended in particular for young, high-performance athletes from around 14 years old,” said Dr. Voigtländer, who is also a cardiologist and medical director of the Agaplesion Bethanien Hospital in Frankfurt.
 

Testing of family

“If sudden cardiac arrest or an unexplained sudden death occurs at a young age in the family, the primary care practitioner must be aware that this could be due to heart diseases that could affect the rest of the family,” said Dr. Voigtländer.

In these cases, primary care practitioners must connect the other family members to specialist outpatient departments that can test for genetic factors, he added. “Many of these genetic diseases can be treated successfully if they are diagnosed promptly.”
 

Lack of knowledge

Dr. Kauferstein, who runs such a specialist outpatient department, said, “unfortunately, many affected families do not know that they should be tested as well. This lack of knowledge can also lead to fatal consequences for relatives.”

For this reason, she believes that it is crucial to provide more information to the general population. Sudden cardiac arrest is often the first sign of an underlying heart disease in young, healthy individuals. “We do see warning signals in our in-depth testing of sudden cardiac arrest cases that have often been overlooked,” said Dr. Kauferstein.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

After 100 years of insulin therapy, teplizumab, an immunotherapy for early-stage type 1 diabetes, has been approved for the first time in the United States and has been shown to delay the manifestation of clinical diabetes by 3 years on average. As a prerequisite for the use of the anti-CD3 antibody teplizumab, patients must undergo a general screening for type 1 diabetes. Whether this prerequisite makes sense was the subject of hot debate among experts at the Diabetes Congress in Berlin.

Anette-Gabriele Ziegler, MD, PhD, director of the Institute for Diabetes Research in Helmholtz Munich, argued that voluntary screening for type 1 diabetes should be included in standard care. “The first immunotherapy that delays type 1 diabetes has been approved in the U.S. for early stage 2. And this early stage can only be identified through prior screening, since no symptoms have manifested by this stage,” she said. This is the only way in which as many people as possible, particularly children, will benefit from the disease-delaying therapy, she added.
 

Two autoantibodies

One biomarker for the early diagnosis of type 1 diabetes is evidence of at least two positive islet cell antibodies. In one study of more than 13,000 children who were observed for 20 years, the specificity of these antibodies was 100%. “Every single child with a positive autoantibody test developed type 1 diabetes later on in their life,” Dr. Ziegler said. “Based on the results of this study, the early stages of type 1 diabetes were added to multiple guidelines.”

The early stage of type 1 diabetes is divided into the following three phases, depending on autoantibody detection and the level of glucose metabolism:

• Early stage 1: Two or more islet autoantibodies and normoglycemia.
• Early stage 2: Two or more islet autoantibodies and dysglycemia.
• Early stage 3: Symptoms, hyperglycemia, insulin therapy.

The aim of the ongoing FR1DA study is to ascertain whether the general population could also be screened for type 1 diabetes using this autoantibody. “Since 2015, children of kindergarten and school age have undergone screening, and to date, more than 170,000 have been tested,” said Dr. Ziegler. “At least two autoantibodies were detected in 0.3% of those screened.”
 

Education and care

The families of the children in whom early-stage type 1 diabetes was diagnosed were invited to take an oral glucose tolerance test (OGTT), to undergo measurement of hemoglobin A1c, and to take part in training and monitoring. “Education and competent, ongoing care are crucial for the efficacy of the screening,” Dr. Ziegler emphasized.

The OGTT revealed that 85% of the FR1DA children were still in early stage 1, another 11% were in early stage 2, and the remaining 4% were in early stage 3.

“Unfortunately, the 4% could no longer benefit from teplizumab, since the medication is not approved for manifest diabetes,” said Dr. Ziegler. “However, the 11% could receive teplizumab immediately, and then later on, the 85%, when they developed stage 2. Therefore, further observation of the children is also important.”

The speed at which the disease progresses from early stage 1 to early stage 2 can be stratified using IA2 antibodies, the 90-minute OGTT glucose value, and the HbA1c value. With regard to progression to clinical type 1 diabetes (stage 3), it was observed that the progression risk for the FR1DA children was similar to that of international birth cohorts with increased genetic risk. “Of course, there is still no 20-year follow-up like for BABYDIAB, DIPP, and DAISY, but as of yet, the progression rate is practically identical,” said Dr. Ziegler.
 

Dubious benefits?

The advantages of screening for type 1 diabetes would not be limited to potential access to preventive therapies and a smooth transition to insulin therapy at the correct point in time, according to Dr. Ziegler. Participation in the FR1DA study dramatically reduced the risk of diabetic ketoacidosis (DKA). Between 2015 and 2023, the overall rate of ketoacidosis associated with the manifestation of clinical type 1 diabetes was 4.3%. In contrast, the general DKA rate in Germany has remained largely unchanged for the last 2 decades at between 20% and 25%.

In addition, the FR1DA children exhibited better beta cell function and better metabolic function at clinical diagnosis of type 1 diabetes. This finding was observed in a comparison with children with a spontaneous diabetes diagnosis from the DiMelli study. “It is important that there is a lot of data that shows how, in the long term, this is associated with a better morbidity and mortality,” said Dr. Ziegler.

Despite the impressive data from the FR1DA study, not all diabetes experts are convinced that a general screening for type 1 diabetes would be beneficial. Beate Karges, MD, PhD, of the Clinic for Pediatric and Adolescent Medicine of the Bethlehem Hospital Stolberg (Germany) and the endocrinology and diabetology department at the University Hospital Aachen (Germany), stressed, “Screening makes sense if the disease is curable in the preclinical phase or if there is a significantly better prognosis in the event of early diagnosis and treatment.”
 

Severe side effects

Even with an early-stage diagnosis, curing type 1 diabetes is impossible. The new anti-CD3 antibody teplizumab merely delays the manifestation of symptoms for 3 years. However, this delay has its price. The summary of product characteristics for teplizumab contains warnings of severe lymphopenia lasting many weeks, cytokine release syndrome, severe infections, and hypersensitivity reactions. Furthermore, vaccinations may not be administered during teplizumab treatment and therefore must be completed in advance.

“Preventing type 1 diabetes is still not possible, we can only delay it, and the long-term efficacy and safety of this immunotherapy are not clear,” said Dr. Karges. She added that a significant reduction in the DKA rate – as observed in the FR1DA study – may be possible even without screening. This possibility was demonstrated by a model project in Stuttgart, Germany, in which the DKA rate was significantly reduced through education alone.
 

Education reduces ketoacidosis

“The families were given information about the early signs of type 1 diabetes during the education investigation. Through this [education], a reduction in the ketoacidosis rate from 28% to 16% was achieved,” said Dr. Karges. It is also known from studies of familial type 1 diabetes that secondary sufferers in the family only exhibit a DKA rate of 7%. “Through education within the family and awareness campaigns, the DKA rate can be reduced by 40%-65%,” said Dr. Karges.

Dr. Karges also doubts whether starting insulin therapy earlier “at the correct point in time” elicits long-term advantages. Secondary sufferers with familial type 1 diabetes have better HbA1c values in the first few years after diagnosis. “But as they progress beyond 2, towards 10 years, the difference in HbA1c values diminishes,” said Dr. Karges.

Whether the patient has DKA at type 1 diabetes diagnosis also seems to make little difference in the long term. “There is also no difference in the HbA1c value in the 2-10 years after diagnosis,” said Dr. Karges. “Glycemic control is not permanently improved in the event that treatment is started early,” she concluded.

“Type 1 diabetes can be delayed with an immune intervention, but to do so, we must also accept possible severe side effects in an otherwise healthy child,” she said. On the other hand, type 1 diabetes can be treated well. “With pumps and continuous glucose monitoring, insulin therapy in children and adolescents has become significantly safer and more effective,” she said.
 

New therapeutic options

Whether voluntary screening for type 1 diabetes eventually finds its way into standard care depends on the further development of preventive medications. Dr. Ziegler stressed that future preventive therapy does not need to be limited to the anti-CD3 antibody teplizumab.

For example, strategies such as high-dose oral insulin therapy are being investigated. Verapamil, which is used to treat hypertension, is also promising, since with it, beta cells were retained in early stage 3, and it improved their function. The fusion protein abatacept fell short of statistical significance in a recently published study. For Dr. Ziegler, one thing remains true. “The therapy of type 1 diabetes is about to undergo a renaissance.”

This article was translated from the Medscape German Edition. A version of this article appeared on Medscape.com.

After 100 years of insulin therapy, teplizumab, an immunotherapy for early-stage type 1 diabetes, has been approved for the first time in the United States and has been shown to delay the manifestation of clinical diabetes by 3 years on average. As a prerequisite for the use of the anti-CD3 antibody teplizumab, patients must undergo a general screening for type 1 diabetes. Whether this prerequisite makes sense was the subject of hot debate among experts at the Diabetes Congress in Berlin.

Anette-Gabriele Ziegler, MD, PhD, director of the Institute for Diabetes Research in Helmholtz Munich, argued that voluntary screening for type 1 diabetes should be included in standard care. “The first immunotherapy that delays type 1 diabetes has been approved in the U.S. for early stage 2. And this early stage can only be identified through prior screening, since no symptoms have manifested by this stage,” she said. This is the only way in which as many people as possible, particularly children, will benefit from the disease-delaying therapy, she added.
 

Two autoantibodies

One biomarker for the early diagnosis of type 1 diabetes is evidence of at least two positive islet cell antibodies. In one study of more than 13,000 children who were observed for 20 years, the specificity of these antibodies was 100%. “Every single child with a positive autoantibody test developed type 1 diabetes later on in their life,” Dr. Ziegler said. “Based on the results of this study, the early stages of type 1 diabetes were added to multiple guidelines.”

The early stage of type 1 diabetes is divided into the following three phases, depending on autoantibody detection and the level of glucose metabolism:

• Early stage 1: Two or more islet autoantibodies and normoglycemia.
• Early stage 2: Two or more islet autoantibodies and dysglycemia.
• Early stage 3: Symptoms, hyperglycemia, insulin therapy.

The aim of the ongoing FR1DA study is to ascertain whether the general population could also be screened for type 1 diabetes using this autoantibody. “Since 2015, children of kindergarten and school age have undergone screening, and to date, more than 170,000 have been tested,” said Dr. Ziegler. “At least two autoantibodies were detected in 0.3% of those screened.”
 

Education and care

The families of the children in whom early-stage type 1 diabetes was diagnosed were invited to take an oral glucose tolerance test (OGTT), to undergo measurement of hemoglobin A1c, and to take part in training and monitoring. “Education and competent, ongoing care are crucial for the efficacy of the screening,” Dr. Ziegler emphasized.

The OGTT revealed that 85% of the FR1DA children were still in early stage 1, another 11% were in early stage 2, and the remaining 4% were in early stage 3.

“Unfortunately, the 4% could no longer benefit from teplizumab, since the medication is not approved for manifest diabetes,” said Dr. Ziegler. “However, the 11% could receive teplizumab immediately, and then later on, the 85%, when they developed stage 2. Therefore, further observation of the children is also important.”

The speed at which the disease progresses from early stage 1 to early stage 2 can be stratified using IA2 antibodies, the 90-minute OGTT glucose value, and the HbA1c value. With regard to progression to clinical type 1 diabetes (stage 3), it was observed that the progression risk for the FR1DA children was similar to that of international birth cohorts with increased genetic risk. “Of course, there is still no 20-year follow-up like for BABYDIAB, DIPP, and DAISY, but as of yet, the progression rate is practically identical,” said Dr. Ziegler.
 

Dubious benefits?

The advantages of screening for type 1 diabetes would not be limited to potential access to preventive therapies and a smooth transition to insulin therapy at the correct point in time, according to Dr. Ziegler. Participation in the FR1DA study dramatically reduced the risk of diabetic ketoacidosis (DKA). Between 2015 and 2023, the overall rate of ketoacidosis associated with the manifestation of clinical type 1 diabetes was 4.3%. In contrast, the general DKA rate in Germany has remained largely unchanged for the last 2 decades at between 20% and 25%.

In addition, the FR1DA children exhibited better beta cell function and better metabolic function at clinical diagnosis of type 1 diabetes. This finding was observed in a comparison with children with a spontaneous diabetes diagnosis from the DiMelli study. “It is important that there is a lot of data that shows how, in the long term, this is associated with a better morbidity and mortality,” said Dr. Ziegler.

Despite the impressive data from the FR1DA study, not all diabetes experts are convinced that a general screening for type 1 diabetes would be beneficial. Beate Karges, MD, PhD, of the Clinic for Pediatric and Adolescent Medicine of the Bethlehem Hospital Stolberg (Germany) and the endocrinology and diabetology department at the University Hospital Aachen (Germany), stressed, “Screening makes sense if the disease is curable in the preclinical phase or if there is a significantly better prognosis in the event of early diagnosis and treatment.”
 

Severe side effects

Even with an early-stage diagnosis, curing type 1 diabetes is impossible. The new anti-CD3 antibody teplizumab merely delays the manifestation of symptoms for 3 years. However, this delay has its price. The summary of product characteristics for teplizumab contains warnings of severe lymphopenia lasting many weeks, cytokine release syndrome, severe infections, and hypersensitivity reactions. Furthermore, vaccinations may not be administered during teplizumab treatment and therefore must be completed in advance.

“Preventing type 1 diabetes is still not possible, we can only delay it, and the long-term efficacy and safety of this immunotherapy are not clear,” said Dr. Karges. She added that a significant reduction in the DKA rate – as observed in the FR1DA study – may be possible even without screening. This possibility was demonstrated by a model project in Stuttgart, Germany, in which the DKA rate was significantly reduced through education alone.
 

Education reduces ketoacidosis

“The families were given information about the early signs of type 1 diabetes during the education investigation. Through this [education], a reduction in the ketoacidosis rate from 28% to 16% was achieved,” said Dr. Karges. It is also known from studies of familial type 1 diabetes that secondary sufferers in the family only exhibit a DKA rate of 7%. “Through education within the family and awareness campaigns, the DKA rate can be reduced by 40%-65%,” said Dr. Karges.

Dr. Karges also doubts whether starting insulin therapy earlier “at the correct point in time” elicits long-term advantages. Secondary sufferers with familial type 1 diabetes have better HbA1c values in the first few years after diagnosis. “But as they progress beyond 2, towards 10 years, the difference in HbA1c values diminishes,” said Dr. Karges.

Whether the patient has DKA at type 1 diabetes diagnosis also seems to make little difference in the long term. “There is also no difference in the HbA1c value in the 2-10 years after diagnosis,” said Dr. Karges. “Glycemic control is not permanently improved in the event that treatment is started early,” she concluded.

“Type 1 diabetes can be delayed with an immune intervention, but to do so, we must also accept possible severe side effects in an otherwise healthy child,” she said. On the other hand, type 1 diabetes can be treated well. “With pumps and continuous glucose monitoring, insulin therapy in children and adolescents has become significantly safer and more effective,” she said.
 

New therapeutic options

Whether voluntary screening for type 1 diabetes eventually finds its way into standard care depends on the further development of preventive medications. Dr. Ziegler stressed that future preventive therapy does not need to be limited to the anti-CD3 antibody teplizumab.

For example, strategies such as high-dose oral insulin therapy are being investigated. Verapamil, which is used to treat hypertension, is also promising, since with it, beta cells were retained in early stage 3, and it improved their function. The fusion protein abatacept fell short of statistical significance in a recently published study. For Dr. Ziegler, one thing remains true. “The therapy of type 1 diabetes is about to undergo a renaissance.”

This article was translated from the Medscape German Edition. A version of this article appeared on Medscape.com.

After 100 years of insulin therapy, teplizumab, an immunotherapy for early-stage type 1 diabetes, has been approved for the first time in the United States and has been shown to delay the manifestation of clinical diabetes by 3 years on average. As a prerequisite for the use of the anti-CD3 antibody teplizumab, patients must undergo a general screening for type 1 diabetes. Whether this prerequisite makes sense was the subject of hot debate among experts at the Diabetes Congress in Berlin.

Anette-Gabriele Ziegler, MD, PhD, director of the Institute for Diabetes Research in Helmholtz Munich, argued that voluntary screening for type 1 diabetes should be included in standard care. “The first immunotherapy that delays type 1 diabetes has been approved in the U.S. for early stage 2. And this early stage can only be identified through prior screening, since no symptoms have manifested by this stage,” she said. This is the only way in which as many people as possible, particularly children, will benefit from the disease-delaying therapy, she added.
 

Two autoantibodies

One biomarker for the early diagnosis of type 1 diabetes is evidence of at least two positive islet cell antibodies. In one study of more than 13,000 children who were observed for 20 years, the specificity of these antibodies was 100%. “Every single child with a positive autoantibody test developed type 1 diabetes later on in their life,” Dr. Ziegler said. “Based on the results of this study, the early stages of type 1 diabetes were added to multiple guidelines.”

The early stage of type 1 diabetes is divided into the following three phases, depending on autoantibody detection and the level of glucose metabolism:

• Early stage 1: Two or more islet autoantibodies and normoglycemia.
• Early stage 2: Two or more islet autoantibodies and dysglycemia.
• Early stage 3: Symptoms, hyperglycemia, insulin therapy.

The aim of the ongoing FR1DA study is to ascertain whether the general population could also be screened for type 1 diabetes using this autoantibody. “Since 2015, children of kindergarten and school age have undergone screening, and to date, more than 170,000 have been tested,” said Dr. Ziegler. “At least two autoantibodies were detected in 0.3% of those screened.”
 

Education and care

The families of the children in whom early-stage type 1 diabetes was diagnosed were invited to take an oral glucose tolerance test (OGTT), to undergo measurement of hemoglobin A1c, and to take part in training and monitoring. “Education and competent, ongoing care are crucial for the efficacy of the screening,” Dr. Ziegler emphasized.

The OGTT revealed that 85% of the FR1DA children were still in early stage 1, another 11% were in early stage 2, and the remaining 4% were in early stage 3.

“Unfortunately, the 4% could no longer benefit from teplizumab, since the medication is not approved for manifest diabetes,” said Dr. Ziegler. “However, the 11% could receive teplizumab immediately, and then later on, the 85%, when they developed stage 2. Therefore, further observation of the children is also important.”

The speed at which the disease progresses from early stage 1 to early stage 2 can be stratified using IA2 antibodies, the 90-minute OGTT glucose value, and the HbA1c value. With regard to progression to clinical type 1 diabetes (stage 3), it was observed that the progression risk for the FR1DA children was similar to that of international birth cohorts with increased genetic risk. “Of course, there is still no 20-year follow-up like for BABYDIAB, DIPP, and DAISY, but as of yet, the progression rate is practically identical,” said Dr. Ziegler.
 

Dubious benefits?

The advantages of screening for type 1 diabetes would not be limited to potential access to preventive therapies and a smooth transition to insulin therapy at the correct point in time, according to Dr. Ziegler. Participation in the FR1DA study dramatically reduced the risk of diabetic ketoacidosis (DKA). Between 2015 and 2023, the overall rate of ketoacidosis associated with the manifestation of clinical type 1 diabetes was 4.3%. In contrast, the general DKA rate in Germany has remained largely unchanged for the last 2 decades at between 20% and 25%.

In addition, the FR1DA children exhibited better beta cell function and better metabolic function at clinical diagnosis of type 1 diabetes. This finding was observed in a comparison with children with a spontaneous diabetes diagnosis from the DiMelli study. “It is important that there is a lot of data that shows how, in the long term, this is associated with a better morbidity and mortality,” said Dr. Ziegler.

Despite the impressive data from the FR1DA study, not all diabetes experts are convinced that a general screening for type 1 diabetes would be beneficial. Beate Karges, MD, PhD, of the Clinic for Pediatric and Adolescent Medicine of the Bethlehem Hospital Stolberg (Germany) and the endocrinology and diabetology department at the University Hospital Aachen (Germany), stressed, “Screening makes sense if the disease is curable in the preclinical phase or if there is a significantly better prognosis in the event of early diagnosis and treatment.”
 

Severe side effects

Even with an early-stage diagnosis, curing type 1 diabetes is impossible. The new anti-CD3 antibody teplizumab merely delays the manifestation of symptoms for 3 years. However, this delay has its price. The summary of product characteristics for teplizumab contains warnings of severe lymphopenia lasting many weeks, cytokine release syndrome, severe infections, and hypersensitivity reactions. Furthermore, vaccinations may not be administered during teplizumab treatment and therefore must be completed in advance.

“Preventing type 1 diabetes is still not possible, we can only delay it, and the long-term efficacy and safety of this immunotherapy are not clear,” said Dr. Karges. She added that a significant reduction in the DKA rate – as observed in the FR1DA study – may be possible even without screening. This possibility was demonstrated by a model project in Stuttgart, Germany, in which the DKA rate was significantly reduced through education alone.
 

Education reduces ketoacidosis

“The families were given information about the early signs of type 1 diabetes during the education investigation. Through this [education], a reduction in the ketoacidosis rate from 28% to 16% was achieved,” said Dr. Karges. It is also known from studies of familial type 1 diabetes that secondary sufferers in the family only exhibit a DKA rate of 7%. “Through education within the family and awareness campaigns, the DKA rate can be reduced by 40%-65%,” said Dr. Karges.

Dr. Karges also doubts whether starting insulin therapy earlier “at the correct point in time” elicits long-term advantages. Secondary sufferers with familial type 1 diabetes have better HbA1c values in the first few years after diagnosis. “But as they progress beyond 2, towards 10 years, the difference in HbA1c values diminishes,” said Dr. Karges.

Whether the patient has DKA at type 1 diabetes diagnosis also seems to make little difference in the long term. “There is also no difference in the HbA1c value in the 2-10 years after diagnosis,” said Dr. Karges. “Glycemic control is not permanently improved in the event that treatment is started early,” she concluded.

“Type 1 diabetes can be delayed with an immune intervention, but to do so, we must also accept possible severe side effects in an otherwise healthy child,” she said. On the other hand, type 1 diabetes can be treated well. “With pumps and continuous glucose monitoring, insulin therapy in children and adolescents has become significantly safer and more effective,” she said.
 

New therapeutic options

Whether voluntary screening for type 1 diabetes eventually finds its way into standard care depends on the further development of preventive medications. Dr. Ziegler stressed that future preventive therapy does not need to be limited to the anti-CD3 antibody teplizumab.

For example, strategies such as high-dose oral insulin therapy are being investigated. Verapamil, which is used to treat hypertension, is also promising, since with it, beta cells were retained in early stage 3, and it improved their function. The fusion protein abatacept fell short of statistical significance in a recently published study. For Dr. Ziegler, one thing remains true. “The therapy of type 1 diabetes is about to undergo a renaissance.”

This article was translated from the Medscape German Edition. A version of this article appeared on Medscape.com.

Irregular and especially long menstrual cycles, particularly in early and mid adulthood, are associated with an increased risk for cardiovascular disease. This finding is demonstrated in a new analysis of the Nurses’ Health Study II.

“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.

Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
 

Cycle disorders’ role

However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.

At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.

“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.

The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.

The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.

The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
 

Significant in adulthood

The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.

Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”

Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.

Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.

“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
 

Classic risk factors?

Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.

It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.

Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.

“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.

The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.

The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”

They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”

For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”

For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.

This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.

Irregular and especially long menstrual cycles, particularly in early and mid adulthood, are associated with an increased risk for cardiovascular disease. This finding is demonstrated in a new analysis of the Nurses’ Health Study II.

“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.

Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
 

Cycle disorders’ role

However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.

At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.

“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.

The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.

The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.

The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
 

Significant in adulthood

The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.

Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”

Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.

Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.

“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
 

Classic risk factors?

Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.

It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.

Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.

“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.

The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.

The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”

They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”

For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”

For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.

This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.

Irregular and especially long menstrual cycles, particularly in early and mid adulthood, are associated with an increased risk for cardiovascular disease. This finding is demonstrated in a new analysis of the Nurses’ Health Study II.

“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.

Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
 

Cycle disorders’ role

However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.

At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.

“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.

The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.

The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.

The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
 

Significant in adulthood

The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.

Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”

Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.

Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.

“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
 

Classic risk factors?

Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.

It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.

Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.

“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.

The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.

The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”

They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”

For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”

For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.

This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.