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WHO declares aspartame as possible carcinogen
Although this means aspartame might cause cancer in humans, the Group 2B classification from the IARC means the evidence is “limited.” A summary of the working group’s evaluation, also published in The Lancet Oncology, explained that the classification was based on data from three studies assessing the link between aspartame intake and primary liver cancer.
Using that evidence, the World Health Organization and Food and Agriculture Organization Joint Expert Committee on Food Additives confirmed its existing stance that aspartame consumption of up to 40 mg/kg of body weight per day – the amount found in 9-14 diet soft drinks – is safe.
The decision, which was anticipated by Reuters in late June, drew praise from an array of experts who weighed in on the study results via the U.K.-based Science Media Centre. Many emphasized the lack of data showing a causal relationship between the low-calorie artificial sweetener and sought to temper any alarmism related to the decision.
“In short the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak,” said Paul Pharoah, MD, PhD, a professor of cancer epidemiology at Cedars-Sinai Medical Center, Los Angeles. “Group 2B is a very conservative classification in that almost any evidence of carcinogenicity, however flawed, will put a chemical in that category or above.”
Other examples of substances classified as Group 2B are extract of aloe vera, diesel oil, and caffeic acid found in coffee and tea, Dr. Pharoah explained, adding that “this is reflected in the view of the [JECFA] who concluded that there was no convincing evidence from experimental animal or human data that aspartame has adverse effects after ingestion.”
“The general public should not be worried about the risk of cancer associated with a chemical classed as Group 2B by IARC,” he stressed.
Alan Boobis, OBE, PhD, similarly noted that the Group 2B classification “reflects a lack of confidence that the data from experimental animals or from humans is sufficiently convincing to reach a clear conclusion that aspartame is carcinogenic.”
“Hence, exposure at current levels would not be anticipated to have any detrimental effects,” added Dr. Boobis, emeritus professor of toxicology, Imperial College London.
The IARC/JECFA opinion is “very welcome” and “ends the speculation about the safety of aspartame,” added Gunter Kuhnle, Dr. rer. nat., a professor of nutrition and food science at the University of Reading (England).
“It is unfortunate that leaking some information might have created unnecessary uncertainty and concern as consumers might be rightfully worried if they are told that something that is in many foods could cause cancer,” Dr. Kuhnle said. “The published opinion puts this into perspective and makes it very clear that there is no cause for concern when consumed at the current amounts.”
The data reviewed by the IARC Working Group included three studies, comprising four prospective cohorts, that “assessed the association of artificially sweetened beverage consumption with liver cancer risk,” the group reported.
The cohort studies – including one conducted within 10 European countries, one that pooled data from two large U.S. cohorts, and a prospective study also conducted in the United States – each “showed positive associations between artificially sweetened beverage consumption and cancer incidence or cancer mortality” in the overall study population or in relevant subgroups.
Although the studies were of “high quality and controlled for many potential confounders,” the Working Group concluded that “chance, bias, or confounding could not be ruled out with reasonable confidence.” Thus, the evidence for cancer in humans was deemed “limited” for hepatocellular carcinoma and “inadequate” for other cancer types.”
Dr. Pharoah and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Boobis is a member of a number of advisory committees in the public and private sectors, including the International Life Science Institute and The Center for Research on Ingredient Safety at Michigan State University.
A version of this article first appeared on Medscape.com.
Although this means aspartame might cause cancer in humans, the Group 2B classification from the IARC means the evidence is “limited.” A summary of the working group’s evaluation, also published in The Lancet Oncology, explained that the classification was based on data from three studies assessing the link between aspartame intake and primary liver cancer.
Using that evidence, the World Health Organization and Food and Agriculture Organization Joint Expert Committee on Food Additives confirmed its existing stance that aspartame consumption of up to 40 mg/kg of body weight per day – the amount found in 9-14 diet soft drinks – is safe.
The decision, which was anticipated by Reuters in late June, drew praise from an array of experts who weighed in on the study results via the U.K.-based Science Media Centre. Many emphasized the lack of data showing a causal relationship between the low-calorie artificial sweetener and sought to temper any alarmism related to the decision.
“In short the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak,” said Paul Pharoah, MD, PhD, a professor of cancer epidemiology at Cedars-Sinai Medical Center, Los Angeles. “Group 2B is a very conservative classification in that almost any evidence of carcinogenicity, however flawed, will put a chemical in that category or above.”
Other examples of substances classified as Group 2B are extract of aloe vera, diesel oil, and caffeic acid found in coffee and tea, Dr. Pharoah explained, adding that “this is reflected in the view of the [JECFA] who concluded that there was no convincing evidence from experimental animal or human data that aspartame has adverse effects after ingestion.”
“The general public should not be worried about the risk of cancer associated with a chemical classed as Group 2B by IARC,” he stressed.
Alan Boobis, OBE, PhD, similarly noted that the Group 2B classification “reflects a lack of confidence that the data from experimental animals or from humans is sufficiently convincing to reach a clear conclusion that aspartame is carcinogenic.”
“Hence, exposure at current levels would not be anticipated to have any detrimental effects,” added Dr. Boobis, emeritus professor of toxicology, Imperial College London.
The IARC/JECFA opinion is “very welcome” and “ends the speculation about the safety of aspartame,” added Gunter Kuhnle, Dr. rer. nat., a professor of nutrition and food science at the University of Reading (England).
“It is unfortunate that leaking some information might have created unnecessary uncertainty and concern as consumers might be rightfully worried if they are told that something that is in many foods could cause cancer,” Dr. Kuhnle said. “The published opinion puts this into perspective and makes it very clear that there is no cause for concern when consumed at the current amounts.”
The data reviewed by the IARC Working Group included three studies, comprising four prospective cohorts, that “assessed the association of artificially sweetened beverage consumption with liver cancer risk,” the group reported.
The cohort studies – including one conducted within 10 European countries, one that pooled data from two large U.S. cohorts, and a prospective study also conducted in the United States – each “showed positive associations between artificially sweetened beverage consumption and cancer incidence or cancer mortality” in the overall study population or in relevant subgroups.
Although the studies were of “high quality and controlled for many potential confounders,” the Working Group concluded that “chance, bias, or confounding could not be ruled out with reasonable confidence.” Thus, the evidence for cancer in humans was deemed “limited” for hepatocellular carcinoma and “inadequate” for other cancer types.”
Dr. Pharoah and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Boobis is a member of a number of advisory committees in the public and private sectors, including the International Life Science Institute and The Center for Research on Ingredient Safety at Michigan State University.
A version of this article first appeared on Medscape.com.
Although this means aspartame might cause cancer in humans, the Group 2B classification from the IARC means the evidence is “limited.” A summary of the working group’s evaluation, also published in The Lancet Oncology, explained that the classification was based on data from three studies assessing the link between aspartame intake and primary liver cancer.
Using that evidence, the World Health Organization and Food and Agriculture Organization Joint Expert Committee on Food Additives confirmed its existing stance that aspartame consumption of up to 40 mg/kg of body weight per day – the amount found in 9-14 diet soft drinks – is safe.
The decision, which was anticipated by Reuters in late June, drew praise from an array of experts who weighed in on the study results via the U.K.-based Science Media Centre. Many emphasized the lack of data showing a causal relationship between the low-calorie artificial sweetener and sought to temper any alarmism related to the decision.
“In short the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak,” said Paul Pharoah, MD, PhD, a professor of cancer epidemiology at Cedars-Sinai Medical Center, Los Angeles. “Group 2B is a very conservative classification in that almost any evidence of carcinogenicity, however flawed, will put a chemical in that category or above.”
Other examples of substances classified as Group 2B are extract of aloe vera, diesel oil, and caffeic acid found in coffee and tea, Dr. Pharoah explained, adding that “this is reflected in the view of the [JECFA] who concluded that there was no convincing evidence from experimental animal or human data that aspartame has adverse effects after ingestion.”
“The general public should not be worried about the risk of cancer associated with a chemical classed as Group 2B by IARC,” he stressed.
Alan Boobis, OBE, PhD, similarly noted that the Group 2B classification “reflects a lack of confidence that the data from experimental animals or from humans is sufficiently convincing to reach a clear conclusion that aspartame is carcinogenic.”
“Hence, exposure at current levels would not be anticipated to have any detrimental effects,” added Dr. Boobis, emeritus professor of toxicology, Imperial College London.
The IARC/JECFA opinion is “very welcome” and “ends the speculation about the safety of aspartame,” added Gunter Kuhnle, Dr. rer. nat., a professor of nutrition and food science at the University of Reading (England).
“It is unfortunate that leaking some information might have created unnecessary uncertainty and concern as consumers might be rightfully worried if they are told that something that is in many foods could cause cancer,” Dr. Kuhnle said. “The published opinion puts this into perspective and makes it very clear that there is no cause for concern when consumed at the current amounts.”
The data reviewed by the IARC Working Group included three studies, comprising four prospective cohorts, that “assessed the association of artificially sweetened beverage consumption with liver cancer risk,” the group reported.
The cohort studies – including one conducted within 10 European countries, one that pooled data from two large U.S. cohorts, and a prospective study also conducted in the United States – each “showed positive associations between artificially sweetened beverage consumption and cancer incidence or cancer mortality” in the overall study population or in relevant subgroups.
Although the studies were of “high quality and controlled for many potential confounders,” the Working Group concluded that “chance, bias, or confounding could not be ruled out with reasonable confidence.” Thus, the evidence for cancer in humans was deemed “limited” for hepatocellular carcinoma and “inadequate” for other cancer types.”
Dr. Pharoah and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Boobis is a member of a number of advisory committees in the public and private sectors, including the International Life Science Institute and The Center for Research on Ingredient Safety at Michigan State University.
A version of this article first appeared on Medscape.com.
FROM THE LANCET ONCOLOGY
Setmelanotide offers significant, long-lasting weight loss
MARSEILLE, FRANCE – , according to results presented at the latest French Pediatric Society conference. The treatment is effective for adults and children alike.
Setmelanotide is the culmination of two decades of research involving the identification of genes involved in early-onset obesity and the characterization of the melanocortin 4 receptor. It became available via early access in 2021.
Currently limited to use in treating obesity linked to a biallelic POMC/PCSK1 or LEPR deficiency, setmelanotide is being tested with respect to other mutations responsible for severe obesity, raising hopes that it will soon be indicated for use in a larger number of patients.
Fewer than 1% of patients who suffer from severe obesity have monogenic forms of obesity. In recent years, the hope for a targeted treatment for patients with these monogenic forms has become a reality.
Although only a small number of patients currently meet the criteria for setmelanotide treatment (namely, those with obesity linked to a biallelic POMC/PCSK1 enzyme or LEPR deficiency and patients with Bardet-Biedl syndrome), there is a real hope that patients with other forms of severe obesity will be able to benefit from this product, including those with heterozygous (not just homozygous) monoallelic variants, who account for more than 10% of patients with severe early-onset obesity.
Restoring satiety signaling
“Setmelanotide is a melanocortin 4 receptor agonist,” said Béatrice Dubern, MD, PhD, pediatrician at Trousseau Hospital, Paris, and member of the French medical research institute (INSERM)/Sorbonne University team on nutrition and obesity. “Its mode of action rests on activation of the leptin-melanocortin signaling pathway in the hypothalamus, which regulates hunger, satiety, energy expenditure, and, therefore, body weight. Rare genetic variants in the leptin-melanocortin pathway are associated with polyphagia and severe early-onset obesity. It is believed that more than 60 genes involved in this leptin-melanocortin pathway are currently associated with obesity.”
In July 2021, the European Medicines Agency approved setmelanotide for daily use via subcutaneous administration.
Weight loss maintained
In phase 3 studies, setmelanotide (melanocortin 4 receptor agonist) demonstrated its effectiveness in reducing weight and hunger for patients with obesity caused by a POMC/PCSK1 or LEPR deficiency.
Twenty-four patients aged 6 years and older showed a significant response to setmelanotide after 1 year of treatment and were included in the extension study. “Significant response” was defined as a reduction in body weight greater than or equal to 10% after 52 weeks for patients aged 18 years and older or a reduction in body mass index (BMI) z-score greater than or equal to 0.3 after 52 weeks for patients younger than 18 years.
Among all patients, the mean variation (standard deviation) in BMI was −24.8% (8.2%, n = 24), −21% (13%, n = 23), and −24% (17.9%, n = 15) at 12, 24, and 36 months, respectively.
For patients aged greater than or equal to 18 years (n = 11), the mean variation (standard deviation) in weight was −25.1% (7.7%, n = 11), −22.9% (12.5%, n = 11), and −24.4% (13.2%, n = 8) at 12, 24, and 36 months, respectively.
For children and adolescents (patients aged < 18 years, n = 13), the mean reduction (standard deviation) in BMI z-score was −1.31 ([0.66], n = 13), −1.10 ([0.79], n = 11), and −1.01 (1.22], n = 4) at 12, 24, and 36 months, respectively.
For patients younger than 18 years, the mean variation in BMI z-score was −1.01 SD after three years on setmelanotide (standard deviation, 1.22 [n = 4]). The mean BMI z-score was +2.42 SD (standard deviation, 1.22 [n = 4]) after 3 years of treatment with setmelanotide.
In sum, the patients who achieved a reduction in body weight of at least 10% or greater than or equal to 0.3 mean variation in BMI z-score after 1 year experienced long-lasting, clinically significant benefit after 3 years. The finding supports the long-term use of setmelanotide for this group.
“We feared that setmelanotide’s effectiveness would decrease over time, but after 3 years, this had not happened, and we are hopeful that this sustained efficacy will be long lasting. The first two patients who took the drug in 2016 have not noticed any loss of efficacy as it stands,” said Dr. Dubern.
This is all the more encouraging. In the study presented at the 2023 pediatric conference, setmelanotide’s safety profile was reassuring, and it was consistent with previous studies. Side effects reported in greater than or equal to 15% of patients include injection site reactions, skin hyperpigmentation, nausea, diarrhea, mood disturbances, abdominal pain, vomiting, gastroenteritis, and spontaneous erection.
In addition to the lack of control group, Dr. Dubern acknowledged one other constraint of this study. “Only the patients who responded to treatment with setmelanotide during early-phase trials (85.7%) were enrolled.”
Dr. Dubern summarized the clinical implications: “In patients with early-onset obesity, starting before 5 years of age, doctors should really be considering the possibility that genetics might be involved in such cases. For confirmation and to seek expert opinion, specialist obesity clinics can be found throughout France. Additionally, the INSERM NutriOmics research team headed by Prof Karine Clément, MD, PhD, Sorbonne University, in conjunction with Prof Christine Poitou, MD, PhD, has developed a diagnostic tool [called] ObsGen for practitioners faced with patients with potentially genetic causes of obesity. We can answer any questions they have about the likelihood of a particular patient having a genetic form of obesity and guide their next steps. Treating patients with genetic obesity early on helps limit the condition worsening during adolescence, prevents related complications, and can reduce the stigmatization and suffering experienced by these people. It’s a huge issue. A clinical trial with setmelanotide is currently being carried out in children over 2 years of age.”
Hypothalamic obesity
During the pediatric conference, another speaker presented the results of a phase 2 study that evaluated the efficacy and tolerability of setmelanotide as a new treatment for hypothalamic obesity. Lesions in the hypothalamus can alter melanocortin 4 receptor pathway signaling and thus lead to hypothalamic obesity. Eighteen patients aged 6-40 years with a BMI greater than or equal to the 95th percentile (for patients aged 6-18 years) or greater than or equal to 35 kg/m2 (for adults aged ≥ 18 years) and hypothalamic obesity (craniopharyngioma or other benign brain tumors, surgical removal, and/or chemotherapy) were enrolled. A significant proportion of patients achieved a reduction of greater than or equal to 5% of their BMI (n = 16, 88.9%, CI 90%, 69%-89%, P < .0001), and 72.2% achieved a reduction of greater than or equal to 10% by week 16. The mean change in BMI was −14.9% (9.6%, n = 17). These early results may justify further studies of setmelanotide in treating hypothalamic obesity.
Dr. Dubern has collaborated with Rhythm Pharmaceuticals and Novo Nordisk.
This article was translated from the Medscape French Edition and a version appeared on Medscape.com.
MARSEILLE, FRANCE – , according to results presented at the latest French Pediatric Society conference. The treatment is effective for adults and children alike.
Setmelanotide is the culmination of two decades of research involving the identification of genes involved in early-onset obesity and the characterization of the melanocortin 4 receptor. It became available via early access in 2021.
Currently limited to use in treating obesity linked to a biallelic POMC/PCSK1 or LEPR deficiency, setmelanotide is being tested with respect to other mutations responsible for severe obesity, raising hopes that it will soon be indicated for use in a larger number of patients.
Fewer than 1% of patients who suffer from severe obesity have monogenic forms of obesity. In recent years, the hope for a targeted treatment for patients with these monogenic forms has become a reality.
Although only a small number of patients currently meet the criteria for setmelanotide treatment (namely, those with obesity linked to a biallelic POMC/PCSK1 enzyme or LEPR deficiency and patients with Bardet-Biedl syndrome), there is a real hope that patients with other forms of severe obesity will be able to benefit from this product, including those with heterozygous (not just homozygous) monoallelic variants, who account for more than 10% of patients with severe early-onset obesity.
Restoring satiety signaling
“Setmelanotide is a melanocortin 4 receptor agonist,” said Béatrice Dubern, MD, PhD, pediatrician at Trousseau Hospital, Paris, and member of the French medical research institute (INSERM)/Sorbonne University team on nutrition and obesity. “Its mode of action rests on activation of the leptin-melanocortin signaling pathway in the hypothalamus, which regulates hunger, satiety, energy expenditure, and, therefore, body weight. Rare genetic variants in the leptin-melanocortin pathway are associated with polyphagia and severe early-onset obesity. It is believed that more than 60 genes involved in this leptin-melanocortin pathway are currently associated with obesity.”
In July 2021, the European Medicines Agency approved setmelanotide for daily use via subcutaneous administration.
Weight loss maintained
In phase 3 studies, setmelanotide (melanocortin 4 receptor agonist) demonstrated its effectiveness in reducing weight and hunger for patients with obesity caused by a POMC/PCSK1 or LEPR deficiency.
Twenty-four patients aged 6 years and older showed a significant response to setmelanotide after 1 year of treatment and were included in the extension study. “Significant response” was defined as a reduction in body weight greater than or equal to 10% after 52 weeks for patients aged 18 years and older or a reduction in body mass index (BMI) z-score greater than or equal to 0.3 after 52 weeks for patients younger than 18 years.
Among all patients, the mean variation (standard deviation) in BMI was −24.8% (8.2%, n = 24), −21% (13%, n = 23), and −24% (17.9%, n = 15) at 12, 24, and 36 months, respectively.
For patients aged greater than or equal to 18 years (n = 11), the mean variation (standard deviation) in weight was −25.1% (7.7%, n = 11), −22.9% (12.5%, n = 11), and −24.4% (13.2%, n = 8) at 12, 24, and 36 months, respectively.
For children and adolescents (patients aged < 18 years, n = 13), the mean reduction (standard deviation) in BMI z-score was −1.31 ([0.66], n = 13), −1.10 ([0.79], n = 11), and −1.01 (1.22], n = 4) at 12, 24, and 36 months, respectively.
For patients younger than 18 years, the mean variation in BMI z-score was −1.01 SD after three years on setmelanotide (standard deviation, 1.22 [n = 4]). The mean BMI z-score was +2.42 SD (standard deviation, 1.22 [n = 4]) after 3 years of treatment with setmelanotide.
In sum, the patients who achieved a reduction in body weight of at least 10% or greater than or equal to 0.3 mean variation in BMI z-score after 1 year experienced long-lasting, clinically significant benefit after 3 years. The finding supports the long-term use of setmelanotide for this group.
“We feared that setmelanotide’s effectiveness would decrease over time, but after 3 years, this had not happened, and we are hopeful that this sustained efficacy will be long lasting. The first two patients who took the drug in 2016 have not noticed any loss of efficacy as it stands,” said Dr. Dubern.
This is all the more encouraging. In the study presented at the 2023 pediatric conference, setmelanotide’s safety profile was reassuring, and it was consistent with previous studies. Side effects reported in greater than or equal to 15% of patients include injection site reactions, skin hyperpigmentation, nausea, diarrhea, mood disturbances, abdominal pain, vomiting, gastroenteritis, and spontaneous erection.
In addition to the lack of control group, Dr. Dubern acknowledged one other constraint of this study. “Only the patients who responded to treatment with setmelanotide during early-phase trials (85.7%) were enrolled.”
Dr. Dubern summarized the clinical implications: “In patients with early-onset obesity, starting before 5 years of age, doctors should really be considering the possibility that genetics might be involved in such cases. For confirmation and to seek expert opinion, specialist obesity clinics can be found throughout France. Additionally, the INSERM NutriOmics research team headed by Prof Karine Clément, MD, PhD, Sorbonne University, in conjunction with Prof Christine Poitou, MD, PhD, has developed a diagnostic tool [called] ObsGen for practitioners faced with patients with potentially genetic causes of obesity. We can answer any questions they have about the likelihood of a particular patient having a genetic form of obesity and guide their next steps. Treating patients with genetic obesity early on helps limit the condition worsening during adolescence, prevents related complications, and can reduce the stigmatization and suffering experienced by these people. It’s a huge issue. A clinical trial with setmelanotide is currently being carried out in children over 2 years of age.”
Hypothalamic obesity
During the pediatric conference, another speaker presented the results of a phase 2 study that evaluated the efficacy and tolerability of setmelanotide as a new treatment for hypothalamic obesity. Lesions in the hypothalamus can alter melanocortin 4 receptor pathway signaling and thus lead to hypothalamic obesity. Eighteen patients aged 6-40 years with a BMI greater than or equal to the 95th percentile (for patients aged 6-18 years) or greater than or equal to 35 kg/m2 (for adults aged ≥ 18 years) and hypothalamic obesity (craniopharyngioma or other benign brain tumors, surgical removal, and/or chemotherapy) were enrolled. A significant proportion of patients achieved a reduction of greater than or equal to 5% of their BMI (n = 16, 88.9%, CI 90%, 69%-89%, P < .0001), and 72.2% achieved a reduction of greater than or equal to 10% by week 16. The mean change in BMI was −14.9% (9.6%, n = 17). These early results may justify further studies of setmelanotide in treating hypothalamic obesity.
Dr. Dubern has collaborated with Rhythm Pharmaceuticals and Novo Nordisk.
This article was translated from the Medscape French Edition and a version appeared on Medscape.com.
MARSEILLE, FRANCE – , according to results presented at the latest French Pediatric Society conference. The treatment is effective for adults and children alike.
Setmelanotide is the culmination of two decades of research involving the identification of genes involved in early-onset obesity and the characterization of the melanocortin 4 receptor. It became available via early access in 2021.
Currently limited to use in treating obesity linked to a biallelic POMC/PCSK1 or LEPR deficiency, setmelanotide is being tested with respect to other mutations responsible for severe obesity, raising hopes that it will soon be indicated for use in a larger number of patients.
Fewer than 1% of patients who suffer from severe obesity have monogenic forms of obesity. In recent years, the hope for a targeted treatment for patients with these monogenic forms has become a reality.
Although only a small number of patients currently meet the criteria for setmelanotide treatment (namely, those with obesity linked to a biallelic POMC/PCSK1 enzyme or LEPR deficiency and patients with Bardet-Biedl syndrome), there is a real hope that patients with other forms of severe obesity will be able to benefit from this product, including those with heterozygous (not just homozygous) monoallelic variants, who account for more than 10% of patients with severe early-onset obesity.
Restoring satiety signaling
“Setmelanotide is a melanocortin 4 receptor agonist,” said Béatrice Dubern, MD, PhD, pediatrician at Trousseau Hospital, Paris, and member of the French medical research institute (INSERM)/Sorbonne University team on nutrition and obesity. “Its mode of action rests on activation of the leptin-melanocortin signaling pathway in the hypothalamus, which regulates hunger, satiety, energy expenditure, and, therefore, body weight. Rare genetic variants in the leptin-melanocortin pathway are associated with polyphagia and severe early-onset obesity. It is believed that more than 60 genes involved in this leptin-melanocortin pathway are currently associated with obesity.”
In July 2021, the European Medicines Agency approved setmelanotide for daily use via subcutaneous administration.
Weight loss maintained
In phase 3 studies, setmelanotide (melanocortin 4 receptor agonist) demonstrated its effectiveness in reducing weight and hunger for patients with obesity caused by a POMC/PCSK1 or LEPR deficiency.
Twenty-four patients aged 6 years and older showed a significant response to setmelanotide after 1 year of treatment and were included in the extension study. “Significant response” was defined as a reduction in body weight greater than or equal to 10% after 52 weeks for patients aged 18 years and older or a reduction in body mass index (BMI) z-score greater than or equal to 0.3 after 52 weeks for patients younger than 18 years.
Among all patients, the mean variation (standard deviation) in BMI was −24.8% (8.2%, n = 24), −21% (13%, n = 23), and −24% (17.9%, n = 15) at 12, 24, and 36 months, respectively.
For patients aged greater than or equal to 18 years (n = 11), the mean variation (standard deviation) in weight was −25.1% (7.7%, n = 11), −22.9% (12.5%, n = 11), and −24.4% (13.2%, n = 8) at 12, 24, and 36 months, respectively.
For children and adolescents (patients aged < 18 years, n = 13), the mean reduction (standard deviation) in BMI z-score was −1.31 ([0.66], n = 13), −1.10 ([0.79], n = 11), and −1.01 (1.22], n = 4) at 12, 24, and 36 months, respectively.
For patients younger than 18 years, the mean variation in BMI z-score was −1.01 SD after three years on setmelanotide (standard deviation, 1.22 [n = 4]). The mean BMI z-score was +2.42 SD (standard deviation, 1.22 [n = 4]) after 3 years of treatment with setmelanotide.
In sum, the patients who achieved a reduction in body weight of at least 10% or greater than or equal to 0.3 mean variation in BMI z-score after 1 year experienced long-lasting, clinically significant benefit after 3 years. The finding supports the long-term use of setmelanotide for this group.
“We feared that setmelanotide’s effectiveness would decrease over time, but after 3 years, this had not happened, and we are hopeful that this sustained efficacy will be long lasting. The first two patients who took the drug in 2016 have not noticed any loss of efficacy as it stands,” said Dr. Dubern.
This is all the more encouraging. In the study presented at the 2023 pediatric conference, setmelanotide’s safety profile was reassuring, and it was consistent with previous studies. Side effects reported in greater than or equal to 15% of patients include injection site reactions, skin hyperpigmentation, nausea, diarrhea, mood disturbances, abdominal pain, vomiting, gastroenteritis, and spontaneous erection.
In addition to the lack of control group, Dr. Dubern acknowledged one other constraint of this study. “Only the patients who responded to treatment with setmelanotide during early-phase trials (85.7%) were enrolled.”
Dr. Dubern summarized the clinical implications: “In patients with early-onset obesity, starting before 5 years of age, doctors should really be considering the possibility that genetics might be involved in such cases. For confirmation and to seek expert opinion, specialist obesity clinics can be found throughout France. Additionally, the INSERM NutriOmics research team headed by Prof Karine Clément, MD, PhD, Sorbonne University, in conjunction with Prof Christine Poitou, MD, PhD, has developed a diagnostic tool [called] ObsGen for practitioners faced with patients with potentially genetic causes of obesity. We can answer any questions they have about the likelihood of a particular patient having a genetic form of obesity and guide their next steps. Treating patients with genetic obesity early on helps limit the condition worsening during adolescence, prevents related complications, and can reduce the stigmatization and suffering experienced by these people. It’s a huge issue. A clinical trial with setmelanotide is currently being carried out in children over 2 years of age.”
Hypothalamic obesity
During the pediatric conference, another speaker presented the results of a phase 2 study that evaluated the efficacy and tolerability of setmelanotide as a new treatment for hypothalamic obesity. Lesions in the hypothalamus can alter melanocortin 4 receptor pathway signaling and thus lead to hypothalamic obesity. Eighteen patients aged 6-40 years with a BMI greater than or equal to the 95th percentile (for patients aged 6-18 years) or greater than or equal to 35 kg/m2 (for adults aged ≥ 18 years) and hypothalamic obesity (craniopharyngioma or other benign brain tumors, surgical removal, and/or chemotherapy) were enrolled. A significant proportion of patients achieved a reduction of greater than or equal to 5% of their BMI (n = 16, 88.9%, CI 90%, 69%-89%, P < .0001), and 72.2% achieved a reduction of greater than or equal to 10% by week 16. The mean change in BMI was −14.9% (9.6%, n = 17). These early results may justify further studies of setmelanotide in treating hypothalamic obesity.
Dr. Dubern has collaborated with Rhythm Pharmaceuticals and Novo Nordisk.
This article was translated from the Medscape French Edition and a version appeared on Medscape.com.
Gene therapy promising for reversal of hereditary vision loss
who received the therapy as part of an early access program.
Results of a study of more than 60 patients who received lenadogene nolparvovec (Lumevoq, GenSight Biologics) as a unilateral or bilateral intravitreal injection showed that at 2-year follow-up, 60% had experienced a clinically relevant improvement in the number of letters they could read on a visual acuity chart.
The results, said study presenter Chiara La Morgia, MD, PhD, IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy), confirm in a “real-life setting” the efficacy and safety of the treatment as previously shown in clinical trials.
The findings were presented at the Congress of the European Academy of Neurology (EAN) 2023.
Severe disease
LHON is a maternally inherited genetic condition that leads to rapid loss of vision. It is caused by alterations in mitochondrial DNA that increase oxidative stress in retinal ganglion cells, leading to cell damage and death. The m.11778G>A MT-ND4 mutation (MT-ND4-LHON) is the most common and is seen in approximately 75% of LHON patients in Europe and North America.
It also leads to the most severe form of the disease, in which patients experience rapid, progressive, and painless bilateral loss of vision, either simultaneously or sequentially in both eyes. Within 1 year of onset, 97% of patients have bilateral involvement.
Lenadogene nolparvovec uses an adeno-associated virus vector to deliver the wild-type ND4 gene directly to the mitochondrial membrane of the retinal ganglion cells. This compensates for the mutation and leads to protein synthesis and restoration of energy production.
Dr. La Morgia said that, so far, five clinical studies are or have been conducted with the gene therapy with patients in France, Italy, the United Kingdom, and the United States.
In the current analysis, patients who received the therapy as part of an early access program underwent unilateral or bilateral intravitreal injection at a dose of 9x1010 viral genomes per eye. Efficacy and safety data, as well as patient baseline characteristics, were collected.
Between August 2018 and March 2022, 63 patients with MT-ND4-LHON received lenadogene nolparvovec. Individual-level data were pooled and analyzed. The mean age at first injection was 33.7 years; 90.5% of participants were aged 60 years or younger. The majority (77.8%) were male; just over half (55.6%) were from France, while 28.6% were from the United States.
The average disease duration at first injection was 11.3 years. Sixty-seven percent of patients were injected in both eyes, and 81.0% had previously received idebenone, a short-chain benzoquinone, the only treatment for LHON that has marketing authorization.
At 2-year follow-up, there was a marked improvement in best-corrected visual acuity (BCVA) scores. Moreover, among all 90 treated eyes for which data were available, the mean change in BCVA from nadir at 1 year was –0.45 log of the minimum angle of resolution (LogMAR), or +22.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters on a chart.
Among 58 bilaterally treated eyes, the mean improvement was –0.49 LogMAR, or +24.5 ETDRS letters, over the same period. In 32 unilaterally treated eyes, mean improvement was –0.39 LogMAR, or +19.5 ETDRS letters.
Overall, 64.4% of treated eyes showed an improvement from nadir of ≥ 0.3 LogMAR. A clinically relevant response, defined as an improvement of ≥ 10 ETDRS letters, was achieved by 60.0% of patients.
Regarding safety, Dr. La Morgia showed that 42.9% of eyes had at least one episode of intraocular inflammation, a rate she described as “quite high.” The episodes lasted for an average of 155.8 days.
“But all of this inflammation was very easily treatable in a majority of cases without using oral steroids,” she added, “just topical steroids.”
She also noted that in most cases, the inflammation was not severe.
Approval status
Session cochair Gianfranco De Stefano, MD, department of human neuroscience, Sapienza University of Rome, asked Dr. La Morgia about the current approval status of lenadogene nolparvovec.
She said that it was presented to the European Medicines Agency for approval, but the application was withdrawn earlier this year. The “main criticism” was that bilateral improvement was seen even in patients who received only a unilateral injection.
This is “not easily explainable,” said Dr. La Morgia, although it was found that the viral vector was present in the uninjected eye.
There was also a question regarding the heterogeneity of the patient data, which it is hoped will be addressed in future clinical trials.
Commenting after the session, De Stefano said in an interview that the results are “very interesting” and “very promising.”
He pointed out that idebenone may be the only currently available therapy for LHON, but it is “not very effective, and it’s something you give the patient just for the sake of doing something” in light of the possibility that he or she might have “even a small improvement” in eyesight.
However, he believes that lenadogene nolparvovec is a long way from becoming available in the clinic, primarily because longer follow-up is required to determine whether just one injection is enough.
“It may be likely that this gene therapy does not have a long-lasting effect,” he explained.
Currently, the longest follow-up is just 2 years; “I don’t know if there will be a need for repeat injection,” De Stefano said.
No funding was declared. Dr. La Morgia has relationships with Chiesi Farmaceutici, GenSight Biologics, Regulatory Pharma Net, Thenewway, Santhera Pharmaceuticals, First Class srl, Biologix, Stoke Therapeutics, and Reneo.
A version of this article first appeared on Medscape.com.
who received the therapy as part of an early access program.
Results of a study of more than 60 patients who received lenadogene nolparvovec (Lumevoq, GenSight Biologics) as a unilateral or bilateral intravitreal injection showed that at 2-year follow-up, 60% had experienced a clinically relevant improvement in the number of letters they could read on a visual acuity chart.
The results, said study presenter Chiara La Morgia, MD, PhD, IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy), confirm in a “real-life setting” the efficacy and safety of the treatment as previously shown in clinical trials.
The findings were presented at the Congress of the European Academy of Neurology (EAN) 2023.
Severe disease
LHON is a maternally inherited genetic condition that leads to rapid loss of vision. It is caused by alterations in mitochondrial DNA that increase oxidative stress in retinal ganglion cells, leading to cell damage and death. The m.11778G>A MT-ND4 mutation (MT-ND4-LHON) is the most common and is seen in approximately 75% of LHON patients in Europe and North America.
It also leads to the most severe form of the disease, in which patients experience rapid, progressive, and painless bilateral loss of vision, either simultaneously or sequentially in both eyes. Within 1 year of onset, 97% of patients have bilateral involvement.
Lenadogene nolparvovec uses an adeno-associated virus vector to deliver the wild-type ND4 gene directly to the mitochondrial membrane of the retinal ganglion cells. This compensates for the mutation and leads to protein synthesis and restoration of energy production.
Dr. La Morgia said that, so far, five clinical studies are or have been conducted with the gene therapy with patients in France, Italy, the United Kingdom, and the United States.
In the current analysis, patients who received the therapy as part of an early access program underwent unilateral or bilateral intravitreal injection at a dose of 9x1010 viral genomes per eye. Efficacy and safety data, as well as patient baseline characteristics, were collected.
Between August 2018 and March 2022, 63 patients with MT-ND4-LHON received lenadogene nolparvovec. Individual-level data were pooled and analyzed. The mean age at first injection was 33.7 years; 90.5% of participants were aged 60 years or younger. The majority (77.8%) were male; just over half (55.6%) were from France, while 28.6% were from the United States.
The average disease duration at first injection was 11.3 years. Sixty-seven percent of patients were injected in both eyes, and 81.0% had previously received idebenone, a short-chain benzoquinone, the only treatment for LHON that has marketing authorization.
At 2-year follow-up, there was a marked improvement in best-corrected visual acuity (BCVA) scores. Moreover, among all 90 treated eyes for which data were available, the mean change in BCVA from nadir at 1 year was –0.45 log of the minimum angle of resolution (LogMAR), or +22.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters on a chart.
Among 58 bilaterally treated eyes, the mean improvement was –0.49 LogMAR, or +24.5 ETDRS letters, over the same period. In 32 unilaterally treated eyes, mean improvement was –0.39 LogMAR, or +19.5 ETDRS letters.
Overall, 64.4% of treated eyes showed an improvement from nadir of ≥ 0.3 LogMAR. A clinically relevant response, defined as an improvement of ≥ 10 ETDRS letters, was achieved by 60.0% of patients.
Regarding safety, Dr. La Morgia showed that 42.9% of eyes had at least one episode of intraocular inflammation, a rate she described as “quite high.” The episodes lasted for an average of 155.8 days.
“But all of this inflammation was very easily treatable in a majority of cases without using oral steroids,” she added, “just topical steroids.”
She also noted that in most cases, the inflammation was not severe.
Approval status
Session cochair Gianfranco De Stefano, MD, department of human neuroscience, Sapienza University of Rome, asked Dr. La Morgia about the current approval status of lenadogene nolparvovec.
She said that it was presented to the European Medicines Agency for approval, but the application was withdrawn earlier this year. The “main criticism” was that bilateral improvement was seen even in patients who received only a unilateral injection.
This is “not easily explainable,” said Dr. La Morgia, although it was found that the viral vector was present in the uninjected eye.
There was also a question regarding the heterogeneity of the patient data, which it is hoped will be addressed in future clinical trials.
Commenting after the session, De Stefano said in an interview that the results are “very interesting” and “very promising.”
He pointed out that idebenone may be the only currently available therapy for LHON, but it is “not very effective, and it’s something you give the patient just for the sake of doing something” in light of the possibility that he or she might have “even a small improvement” in eyesight.
However, he believes that lenadogene nolparvovec is a long way from becoming available in the clinic, primarily because longer follow-up is required to determine whether just one injection is enough.
“It may be likely that this gene therapy does not have a long-lasting effect,” he explained.
Currently, the longest follow-up is just 2 years; “I don’t know if there will be a need for repeat injection,” De Stefano said.
No funding was declared. Dr. La Morgia has relationships with Chiesi Farmaceutici, GenSight Biologics, Regulatory Pharma Net, Thenewway, Santhera Pharmaceuticals, First Class srl, Biologix, Stoke Therapeutics, and Reneo.
A version of this article first appeared on Medscape.com.
who received the therapy as part of an early access program.
Results of a study of more than 60 patients who received lenadogene nolparvovec (Lumevoq, GenSight Biologics) as a unilateral or bilateral intravitreal injection showed that at 2-year follow-up, 60% had experienced a clinically relevant improvement in the number of letters they could read on a visual acuity chart.
The results, said study presenter Chiara La Morgia, MD, PhD, IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy), confirm in a “real-life setting” the efficacy and safety of the treatment as previously shown in clinical trials.
The findings were presented at the Congress of the European Academy of Neurology (EAN) 2023.
Severe disease
LHON is a maternally inherited genetic condition that leads to rapid loss of vision. It is caused by alterations in mitochondrial DNA that increase oxidative stress in retinal ganglion cells, leading to cell damage and death. The m.11778G>A MT-ND4 mutation (MT-ND4-LHON) is the most common and is seen in approximately 75% of LHON patients in Europe and North America.
It also leads to the most severe form of the disease, in which patients experience rapid, progressive, and painless bilateral loss of vision, either simultaneously or sequentially in both eyes. Within 1 year of onset, 97% of patients have bilateral involvement.
Lenadogene nolparvovec uses an adeno-associated virus vector to deliver the wild-type ND4 gene directly to the mitochondrial membrane of the retinal ganglion cells. This compensates for the mutation and leads to protein synthesis and restoration of energy production.
Dr. La Morgia said that, so far, five clinical studies are or have been conducted with the gene therapy with patients in France, Italy, the United Kingdom, and the United States.
In the current analysis, patients who received the therapy as part of an early access program underwent unilateral or bilateral intravitreal injection at a dose of 9x1010 viral genomes per eye. Efficacy and safety data, as well as patient baseline characteristics, were collected.
Between August 2018 and March 2022, 63 patients with MT-ND4-LHON received lenadogene nolparvovec. Individual-level data were pooled and analyzed. The mean age at first injection was 33.7 years; 90.5% of participants were aged 60 years or younger. The majority (77.8%) were male; just over half (55.6%) were from France, while 28.6% were from the United States.
The average disease duration at first injection was 11.3 years. Sixty-seven percent of patients were injected in both eyes, and 81.0% had previously received idebenone, a short-chain benzoquinone, the only treatment for LHON that has marketing authorization.
At 2-year follow-up, there was a marked improvement in best-corrected visual acuity (BCVA) scores. Moreover, among all 90 treated eyes for which data were available, the mean change in BCVA from nadir at 1 year was –0.45 log of the minimum angle of resolution (LogMAR), or +22.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters on a chart.
Among 58 bilaterally treated eyes, the mean improvement was –0.49 LogMAR, or +24.5 ETDRS letters, over the same period. In 32 unilaterally treated eyes, mean improvement was –0.39 LogMAR, or +19.5 ETDRS letters.
Overall, 64.4% of treated eyes showed an improvement from nadir of ≥ 0.3 LogMAR. A clinically relevant response, defined as an improvement of ≥ 10 ETDRS letters, was achieved by 60.0% of patients.
Regarding safety, Dr. La Morgia showed that 42.9% of eyes had at least one episode of intraocular inflammation, a rate she described as “quite high.” The episodes lasted for an average of 155.8 days.
“But all of this inflammation was very easily treatable in a majority of cases without using oral steroids,” she added, “just topical steroids.”
She also noted that in most cases, the inflammation was not severe.
Approval status
Session cochair Gianfranco De Stefano, MD, department of human neuroscience, Sapienza University of Rome, asked Dr. La Morgia about the current approval status of lenadogene nolparvovec.
She said that it was presented to the European Medicines Agency for approval, but the application was withdrawn earlier this year. The “main criticism” was that bilateral improvement was seen even in patients who received only a unilateral injection.
This is “not easily explainable,” said Dr. La Morgia, although it was found that the viral vector was present in the uninjected eye.
There was also a question regarding the heterogeneity of the patient data, which it is hoped will be addressed in future clinical trials.
Commenting after the session, De Stefano said in an interview that the results are “very interesting” and “very promising.”
He pointed out that idebenone may be the only currently available therapy for LHON, but it is “not very effective, and it’s something you give the patient just for the sake of doing something” in light of the possibility that he or she might have “even a small improvement” in eyesight.
However, he believes that lenadogene nolparvovec is a long way from becoming available in the clinic, primarily because longer follow-up is required to determine whether just one injection is enough.
“It may be likely that this gene therapy does not have a long-lasting effect,” he explained.
Currently, the longest follow-up is just 2 years; “I don’t know if there will be a need for repeat injection,” De Stefano said.
No funding was declared. Dr. La Morgia has relationships with Chiesi Farmaceutici, GenSight Biologics, Regulatory Pharma Net, Thenewway, Santhera Pharmaceuticals, First Class srl, Biologix, Stoke Therapeutics, and Reneo.
A version of this article first appeared on Medscape.com.
FROM EAN 2023
Meta-analysis finds increase in type 1 diabetes incidence, ketoacidosis during COVID pandemic
according to a recent meta-analysis.
The review compared 2 years of data from during the pandemic to data from a prepandemic period, and showed a higher incidence of type 1 diabetes in the first year (incidence rate ratio, 1.14) and second year (IRR, 1.27) of the pandemic. The investigators also found an increase in the incidence of diabetic ketoacidosis (DKA) (IRR, 1.26).
The meta-analysis included 17 studies of 38,149 children and adolescents with newly diagnosed type 1 diabetes. “Putting them all together really gave us more confidence to say this is something that we think is real,” study author Rayzel Shulman, MD, PhD, an endocrinologist at The Hospital for Sick Children in Toronto and associate professor of pediatrics at the University of Toronto, said in an interview.
The study was published in JAMA Network Open.
Increased incidence
The investigators reviewed 42 studies, including 17 that examined rates of type 1 diabetes incidence, 10 on type 2 diabetes, and 15 on DKA. The included studies all had a minimum observation period of 12 months during the pandemic and at least 12 months before it. Relative to the prepandemic period, the meta-analysis found higher rates of type 1 diabetes and DKA during the pandemic.
The review was conducted in response to questions about the methodology of study results suggesting an association between the COVID-19 pandemic and the incidence of diabetes, according to Dr. Shulman.
Although this is not the first review of studies on the connection between diabetes and COVID-19, it adds to the literature by extending the study period to 2 years of the pandemic. The longer time frame helps address potential seasonal differences in incidence and increases confidence in the results.
The investigators also sought to look at the incidence of type 2 diabetes in children but found few studies that met the study criteria. Although some studies reported rates of type 2 diabetes, most lacked information about the population, specifically, the “denominator” needed for findings regarding any association with the COVID-19 pandemic.
With greater confidence in the increased incidence of type 1 diabetes, Dr. Shulman emphasized a need to ensure sufficient resources to care for newly diagnosed patients, including education and support for families.
The study’s secondary outcome was the change in incidence rate of DKA among children with newly diagnosed diabetes. Data reported in 15 studies showed a 26% increase in DKA incidence during the first year of the pandemic.
“DKA is a serious and life-threatening condition that is preventable,” said Dr. Shulman. Symptoms of type 1 diabetes include increased thirst and urination, weight loss, and fatigue. If parents or caregivers notice these signs, Dr. Shulman advises them to seek care immediately to reduce the risk of DKA.
Possible mechanisms
In a comment, Elizabeth Sellers, MD, an endocrinologist at the Children’s Hospital Research Institute of Manitoba and associate professor of pediatrics at the University of Manitoba, both in Winnipeg, said the study’s findings on DKA are an important reminder to be attentive to symptoms of diabetes. Dr. Sellers did not participate in the meta-analysis.
One possible explanation for the increase is a hesitancy to seek care among parents and caregivers during the pandemic. “I think we use that information and turn it into a positive,” said Dr. Sellers, by increasing recognition of the symptoms. Dr. Sellers, whose research is included in the review, is part of an initiative by the Canadian Pediatric Endocrine Group to increase diabetes awareness.
The study provides important findings, particularly the second-year results, but is not designed to answer why there has been an increase in diabetes incidence, said Dr. Sellers. “You have to identify the problem first and then you can go back and look at mechanisms.”
The meta-analysis did not seek to draw conclusions about the underlying mechanisms that would explain changes in diabetes incidence but rather indicates a need for further studies to seek a better understanding of the connection. Several theories may be considered, wrote Clemens Kamrath, MD, of the Centre of Child and Adolescent Medicine at Justus Liebig University in Giessen, Germany, and colleagues in an accompanying editorial.
Studies have suggested a direct effect of infections such as COVID-19, whereby the virus damages insulin-producing beta cells. However, the commentary notes these studies do not account for asymptomatic infections among children.
Dr. Kamrath and colleagues also considered the indirect effects of the COVID-19 pandemic, which they indicate may be more likely than direct effects. These indirect effects include autoimmunity and environmental changes that occurred during the pandemic.
Researchers will need to continue monitoring the data to see if the trend persists and continue working to determine the mechanisms, said Dr. Schulman. “I don’t think this is the end of the story.”
The study was supported in part by grant funding from the department of pediatrics at The Hospital for Sick Children. Dr. Shulman, Dr. Sellers, and Dr. Kamrath reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a recent meta-analysis.
The review compared 2 years of data from during the pandemic to data from a prepandemic period, and showed a higher incidence of type 1 diabetes in the first year (incidence rate ratio, 1.14) and second year (IRR, 1.27) of the pandemic. The investigators also found an increase in the incidence of diabetic ketoacidosis (DKA) (IRR, 1.26).
The meta-analysis included 17 studies of 38,149 children and adolescents with newly diagnosed type 1 diabetes. “Putting them all together really gave us more confidence to say this is something that we think is real,” study author Rayzel Shulman, MD, PhD, an endocrinologist at The Hospital for Sick Children in Toronto and associate professor of pediatrics at the University of Toronto, said in an interview.
The study was published in JAMA Network Open.
Increased incidence
The investigators reviewed 42 studies, including 17 that examined rates of type 1 diabetes incidence, 10 on type 2 diabetes, and 15 on DKA. The included studies all had a minimum observation period of 12 months during the pandemic and at least 12 months before it. Relative to the prepandemic period, the meta-analysis found higher rates of type 1 diabetes and DKA during the pandemic.
The review was conducted in response to questions about the methodology of study results suggesting an association between the COVID-19 pandemic and the incidence of diabetes, according to Dr. Shulman.
Although this is not the first review of studies on the connection between diabetes and COVID-19, it adds to the literature by extending the study period to 2 years of the pandemic. The longer time frame helps address potential seasonal differences in incidence and increases confidence in the results.
The investigators also sought to look at the incidence of type 2 diabetes in children but found few studies that met the study criteria. Although some studies reported rates of type 2 diabetes, most lacked information about the population, specifically, the “denominator” needed for findings regarding any association with the COVID-19 pandemic.
With greater confidence in the increased incidence of type 1 diabetes, Dr. Shulman emphasized a need to ensure sufficient resources to care for newly diagnosed patients, including education and support for families.
The study’s secondary outcome was the change in incidence rate of DKA among children with newly diagnosed diabetes. Data reported in 15 studies showed a 26% increase in DKA incidence during the first year of the pandemic.
“DKA is a serious and life-threatening condition that is preventable,” said Dr. Shulman. Symptoms of type 1 diabetes include increased thirst and urination, weight loss, and fatigue. If parents or caregivers notice these signs, Dr. Shulman advises them to seek care immediately to reduce the risk of DKA.
Possible mechanisms
In a comment, Elizabeth Sellers, MD, an endocrinologist at the Children’s Hospital Research Institute of Manitoba and associate professor of pediatrics at the University of Manitoba, both in Winnipeg, said the study’s findings on DKA are an important reminder to be attentive to symptoms of diabetes. Dr. Sellers did not participate in the meta-analysis.
One possible explanation for the increase is a hesitancy to seek care among parents and caregivers during the pandemic. “I think we use that information and turn it into a positive,” said Dr. Sellers, by increasing recognition of the symptoms. Dr. Sellers, whose research is included in the review, is part of an initiative by the Canadian Pediatric Endocrine Group to increase diabetes awareness.
The study provides important findings, particularly the second-year results, but is not designed to answer why there has been an increase in diabetes incidence, said Dr. Sellers. “You have to identify the problem first and then you can go back and look at mechanisms.”
The meta-analysis did not seek to draw conclusions about the underlying mechanisms that would explain changes in diabetes incidence but rather indicates a need for further studies to seek a better understanding of the connection. Several theories may be considered, wrote Clemens Kamrath, MD, of the Centre of Child and Adolescent Medicine at Justus Liebig University in Giessen, Germany, and colleagues in an accompanying editorial.
Studies have suggested a direct effect of infections such as COVID-19, whereby the virus damages insulin-producing beta cells. However, the commentary notes these studies do not account for asymptomatic infections among children.
Dr. Kamrath and colleagues also considered the indirect effects of the COVID-19 pandemic, which they indicate may be more likely than direct effects. These indirect effects include autoimmunity and environmental changes that occurred during the pandemic.
Researchers will need to continue monitoring the data to see if the trend persists and continue working to determine the mechanisms, said Dr. Schulman. “I don’t think this is the end of the story.”
The study was supported in part by grant funding from the department of pediatrics at The Hospital for Sick Children. Dr. Shulman, Dr. Sellers, and Dr. Kamrath reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a recent meta-analysis.
The review compared 2 years of data from during the pandemic to data from a prepandemic period, and showed a higher incidence of type 1 diabetes in the first year (incidence rate ratio, 1.14) and second year (IRR, 1.27) of the pandemic. The investigators also found an increase in the incidence of diabetic ketoacidosis (DKA) (IRR, 1.26).
The meta-analysis included 17 studies of 38,149 children and adolescents with newly diagnosed type 1 diabetes. “Putting them all together really gave us more confidence to say this is something that we think is real,” study author Rayzel Shulman, MD, PhD, an endocrinologist at The Hospital for Sick Children in Toronto and associate professor of pediatrics at the University of Toronto, said in an interview.
The study was published in JAMA Network Open.
Increased incidence
The investigators reviewed 42 studies, including 17 that examined rates of type 1 diabetes incidence, 10 on type 2 diabetes, and 15 on DKA. The included studies all had a minimum observation period of 12 months during the pandemic and at least 12 months before it. Relative to the prepandemic period, the meta-analysis found higher rates of type 1 diabetes and DKA during the pandemic.
The review was conducted in response to questions about the methodology of study results suggesting an association between the COVID-19 pandemic and the incidence of diabetes, according to Dr. Shulman.
Although this is not the first review of studies on the connection between diabetes and COVID-19, it adds to the literature by extending the study period to 2 years of the pandemic. The longer time frame helps address potential seasonal differences in incidence and increases confidence in the results.
The investigators also sought to look at the incidence of type 2 diabetes in children but found few studies that met the study criteria. Although some studies reported rates of type 2 diabetes, most lacked information about the population, specifically, the “denominator” needed for findings regarding any association with the COVID-19 pandemic.
With greater confidence in the increased incidence of type 1 diabetes, Dr. Shulman emphasized a need to ensure sufficient resources to care for newly diagnosed patients, including education and support for families.
The study’s secondary outcome was the change in incidence rate of DKA among children with newly diagnosed diabetes. Data reported in 15 studies showed a 26% increase in DKA incidence during the first year of the pandemic.
“DKA is a serious and life-threatening condition that is preventable,” said Dr. Shulman. Symptoms of type 1 diabetes include increased thirst and urination, weight loss, and fatigue. If parents or caregivers notice these signs, Dr. Shulman advises them to seek care immediately to reduce the risk of DKA.
Possible mechanisms
In a comment, Elizabeth Sellers, MD, an endocrinologist at the Children’s Hospital Research Institute of Manitoba and associate professor of pediatrics at the University of Manitoba, both in Winnipeg, said the study’s findings on DKA are an important reminder to be attentive to symptoms of diabetes. Dr. Sellers did not participate in the meta-analysis.
One possible explanation for the increase is a hesitancy to seek care among parents and caregivers during the pandemic. “I think we use that information and turn it into a positive,” said Dr. Sellers, by increasing recognition of the symptoms. Dr. Sellers, whose research is included in the review, is part of an initiative by the Canadian Pediatric Endocrine Group to increase diabetes awareness.
The study provides important findings, particularly the second-year results, but is not designed to answer why there has been an increase in diabetes incidence, said Dr. Sellers. “You have to identify the problem first and then you can go back and look at mechanisms.”
The meta-analysis did not seek to draw conclusions about the underlying mechanisms that would explain changes in diabetes incidence but rather indicates a need for further studies to seek a better understanding of the connection. Several theories may be considered, wrote Clemens Kamrath, MD, of the Centre of Child and Adolescent Medicine at Justus Liebig University in Giessen, Germany, and colleagues in an accompanying editorial.
Studies have suggested a direct effect of infections such as COVID-19, whereby the virus damages insulin-producing beta cells. However, the commentary notes these studies do not account for asymptomatic infections among children.
Dr. Kamrath and colleagues also considered the indirect effects of the COVID-19 pandemic, which they indicate may be more likely than direct effects. These indirect effects include autoimmunity and environmental changes that occurred during the pandemic.
Researchers will need to continue monitoring the data to see if the trend persists and continue working to determine the mechanisms, said Dr. Schulman. “I don’t think this is the end of the story.”
The study was supported in part by grant funding from the department of pediatrics at The Hospital for Sick Children. Dr. Shulman, Dr. Sellers, and Dr. Kamrath reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
More children missing developmental milestones: Survey
Nearly 9 out of every 100 U.S. children are now diagnosed with a developmental disability, according to updated figures from the CDC.
Developmental disabilities include autism, intellectual disabilities such as Down syndrome, and a range of other diagnoses related to missing developmental milestones in how a child plays, learns, or speaks.
The newly reported increase amounts to just over 1 percentage point from 2019 to 2021. In 2019, the rate of developmental disability diagnoses was about 7 in 100 children. The latest figures are from 2021 data, published this week after the CDC finished analyzing responses to the National Health Survey.
Among children ages 3-17 years old in 2021, the survey showed that:
- 1.7% had an intellectual disability.
- 3.1% had autism spectrum disorder.
- 6.1% had a diagnosis of “other developmental delay.”
No significant change was seen from 2019 to 2021 in how common it was for survey respondents to report children having autism or an intellectual disability. The overall increase was driven by a jump in reports from parents that a doctor or health professional told them their child had “any other developmental delay,” excluding autism spectrum disorder or an intellectual disability.
“A lot of times developmental delays might be temporary diagnoses that evolve into something like autism, potentially, or intellectual disability. But also a lot of times children do age out of those,” lead report author and CDC statistician Benjamin Zablotsky, PhD, told CBS News.
The CDC offers an app called Milestone Tracker to help parents watch for signs of developmental delays, in addition to operating a public health education program called “Learn the Signs. Act Early.”
The new report showed that boys were nearly twice as likely as girls to have any developmental delay, a pattern that was magnified when looking specifically at autism diagnoses. Boys were more than three times as likely as girls to be diagnosed with autism spectrum disorder. The rate of autism among boys was 4.7%, compared with 1.5% among girls.
While these latest survey results showed consistent rates of autism from 2019 to 2021, a different CDC report earlier this year showed an alarming jump in the rate of autism spectrum disorder among 8-year-olds. That report, which compared data from 2008 to 2020, showed the rate of autism among 8-year-olds rose during those 12 years from 1 in 88 kids to 1 in 36 kids.
The two analyses also differed in their findings regarding prevalence of autism when looking at children by race and ethnicity. The report from earlier this year showed that Black and Hispanic children were more likely to be diagnosed with autism, compared with White children. This latest report did not find any differences in the prevalence of autism based on a child’s race or ethnicity.
A version of this article appeared on WebMD.com.
Nearly 9 out of every 100 U.S. children are now diagnosed with a developmental disability, according to updated figures from the CDC.
Developmental disabilities include autism, intellectual disabilities such as Down syndrome, and a range of other diagnoses related to missing developmental milestones in how a child plays, learns, or speaks.
The newly reported increase amounts to just over 1 percentage point from 2019 to 2021. In 2019, the rate of developmental disability diagnoses was about 7 in 100 children. The latest figures are from 2021 data, published this week after the CDC finished analyzing responses to the National Health Survey.
Among children ages 3-17 years old in 2021, the survey showed that:
- 1.7% had an intellectual disability.
- 3.1% had autism spectrum disorder.
- 6.1% had a diagnosis of “other developmental delay.”
No significant change was seen from 2019 to 2021 in how common it was for survey respondents to report children having autism or an intellectual disability. The overall increase was driven by a jump in reports from parents that a doctor or health professional told them their child had “any other developmental delay,” excluding autism spectrum disorder or an intellectual disability.
“A lot of times developmental delays might be temporary diagnoses that evolve into something like autism, potentially, or intellectual disability. But also a lot of times children do age out of those,” lead report author and CDC statistician Benjamin Zablotsky, PhD, told CBS News.
The CDC offers an app called Milestone Tracker to help parents watch for signs of developmental delays, in addition to operating a public health education program called “Learn the Signs. Act Early.”
The new report showed that boys were nearly twice as likely as girls to have any developmental delay, a pattern that was magnified when looking specifically at autism diagnoses. Boys were more than three times as likely as girls to be diagnosed with autism spectrum disorder. The rate of autism among boys was 4.7%, compared with 1.5% among girls.
While these latest survey results showed consistent rates of autism from 2019 to 2021, a different CDC report earlier this year showed an alarming jump in the rate of autism spectrum disorder among 8-year-olds. That report, which compared data from 2008 to 2020, showed the rate of autism among 8-year-olds rose during those 12 years from 1 in 88 kids to 1 in 36 kids.
The two analyses also differed in their findings regarding prevalence of autism when looking at children by race and ethnicity. The report from earlier this year showed that Black and Hispanic children were more likely to be diagnosed with autism, compared with White children. This latest report did not find any differences in the prevalence of autism based on a child’s race or ethnicity.
A version of this article appeared on WebMD.com.
Nearly 9 out of every 100 U.S. children are now diagnosed with a developmental disability, according to updated figures from the CDC.
Developmental disabilities include autism, intellectual disabilities such as Down syndrome, and a range of other diagnoses related to missing developmental milestones in how a child plays, learns, or speaks.
The newly reported increase amounts to just over 1 percentage point from 2019 to 2021. In 2019, the rate of developmental disability diagnoses was about 7 in 100 children. The latest figures are from 2021 data, published this week after the CDC finished analyzing responses to the National Health Survey.
Among children ages 3-17 years old in 2021, the survey showed that:
- 1.7% had an intellectual disability.
- 3.1% had autism spectrum disorder.
- 6.1% had a diagnosis of “other developmental delay.”
No significant change was seen from 2019 to 2021 in how common it was for survey respondents to report children having autism or an intellectual disability. The overall increase was driven by a jump in reports from parents that a doctor or health professional told them their child had “any other developmental delay,” excluding autism spectrum disorder or an intellectual disability.
“A lot of times developmental delays might be temporary diagnoses that evolve into something like autism, potentially, or intellectual disability. But also a lot of times children do age out of those,” lead report author and CDC statistician Benjamin Zablotsky, PhD, told CBS News.
The CDC offers an app called Milestone Tracker to help parents watch for signs of developmental delays, in addition to operating a public health education program called “Learn the Signs. Act Early.”
The new report showed that boys were nearly twice as likely as girls to have any developmental delay, a pattern that was magnified when looking specifically at autism diagnoses. Boys were more than three times as likely as girls to be diagnosed with autism spectrum disorder. The rate of autism among boys was 4.7%, compared with 1.5% among girls.
While these latest survey results showed consistent rates of autism from 2019 to 2021, a different CDC report earlier this year showed an alarming jump in the rate of autism spectrum disorder among 8-year-olds. That report, which compared data from 2008 to 2020, showed the rate of autism among 8-year-olds rose during those 12 years from 1 in 88 kids to 1 in 36 kids.
The two analyses also differed in their findings regarding prevalence of autism when looking at children by race and ethnicity. The report from earlier this year showed that Black and Hispanic children were more likely to be diagnosed with autism, compared with White children. This latest report did not find any differences in the prevalence of autism based on a child’s race or ethnicity.
A version of this article appeared on WebMD.com.
Alzheimer’s Disease Treatment
Impostor syndrome is a risk for doctors of all ages
COVID-19 imposed challenges on health care professionals and systems by forcing changes in how doctors organize themselves professionally as well as in their relationships with patients and in their expectations (realistic or not) of their roles. The situation was bound to generate high rates of frustration and discomfort among younger and older physicians. It was compounded by a generational transition of the profession, which was accelerated by the virus. It was not managed by the decision-makers and was painful for doctors and patients.
Impostor syndrome (IS) is a psychological construct characterized by the persistent belief that one’s success is undeserved, rather than stemming from personal effort, skill, and ability. The phenomenon is common among medics for various reasons, including professional burnout. Recent studies have helped to better define the extent and characteristic features of the syndrome, as well as efforts to combat it.
Doctors and burnout
Although occupational burnout among physicians is a systemic issue primarily attributable to problems in the practice environment, professional norms and aspects of medical culture often contribute to the distress that individual physicians experience.
These dimensions have been well characterized and include suggestions that physicians should be impervious to normal human limitations (that is, superhuman), that work should always come first, and that seeking help is a sign of weakness. In aggregate, these attitudes lead many physicians to engage in unhealthy levels of self-sacrifice, manifested by excessive work hours, anxiety about missing something that would benefit their patients, and prioritizing work over personal health. These factors are familiar to many hospital-based and family physicians.
The impostor phenomenon
The impostor phenomenon (IP) is a psychological experience of intellectual and professional fraud. Individuals who suffer from it believe that others have inflated perceptions of the individual’s abilities and fear being judged. This fear persists despite continual proof of the individual’s successes. These people ignore praise, are highly self-critical, and attribute their successes to external factors, such as luck, hard work, or receiving help from others, rather than to qualities such as skill, intelligence, or ability.
IP is common among men and women. Some studies suggest it may be more prevalent among women. Studies across industries suggest that the phenomenon is associated with personal consequences (for example, low emotional well-being, problems with work-life integration, anxiety, depression, suicide) and professional consequences (for example, impaired job performance, occupational burnout). Studies involving U.S. medical students have revealed that more than one in four medical students experience IP and that those who experience it are at higher risk for burnout.
Surveying IS
IS, which is not a formal psychiatric diagnosis, is defined as having feelings of uncertainty, inadequacy, and being undeserving of one’s achievements despite evidence to the contrary. There are five subtypes of IS:
- Perfectionist: insecurity related to self-imposed, unachievable goals
- Expert: feeling inadequate from lacking sufficient knowledge
- Superperson: assuming excessive workloads just to feel okay among peers
- Natural genius: experiencing shame when it takes effort to develop a skill
- Soloist: believing that requesting help is a sign of weakness
Risk factors
Studies suggest that IS is a problem early in the physician training process. There is limited information on IS among physicians in practice.
Because transitions represent a risk factor for IP, the frequent rotation between clerkships and being a “perpetual novice” during medical school training may contribute to the high prevalence. Qualitative studies suggest that, once in practice, other professional experiences (for example, unfavorable patient outcomes, patient complaints, rejection of grants or manuscripts, and poor teaching evaluations or patient satisfaction scores) may contribute to IP.
Impact on doctors
Several methods have been used to classify how much the phenomenon interferes with a person’s life. The Clance Impostor Phenomenon Scale is a 20-item scale that asks respondents to indicate how well each item characterizes their experience on a 5-point scale. Options range from “not at all” to “very true.” The sum of responses to the individual items is used to create an aggregate score (IP score). The higher the score, the more frequently and seriously IP interferes with a person’s life.
A simplified version of the IP score was used in a study of 3,237 U.S. doctors that investigated the association between IS and burnout among doctors and to compare their rates of IS with those of other professionals.
Mean IP scores were higher for female physicians than for male physicians (mean, 10.91 vs. 9.12; P < .001). Scores decreased with age and were lower among those who were married or widowed.
With respect to professional characteristics, IP scores were greater among those in academic practice or who worked in the Veterans Affairs medical system and decreased with years in practice.
The highest IP scores were among pediatric subspecialists, general pediatricians, and emergency medicine physicians. Scores were lowest among ophthalmologists, radiologists, and orthopedic surgeons. IP has been independently associated with the risk of burnout and low professional fulfillment.
Lessening the impact
An article commenting on the study highlighted the following expert practice strategies that doctors can use to reduce the impact of IS in their professional life.
- Review and celebrate feats that have led to your professional role.
- Share concerns with trusted colleagues who can validate your accomplishments and normalize your feelings by reporting their own struggles with IS.
- Combat perfectionism by accepting that it is okay to be good enough when meeting the challenges of a demanding profession.
- Exercise self-compassion as an alternative to relying on an external locus of self-worth.
- Understand that IS may be common, especially during transitions, such as when entering medical school, graduate medical training, or starting a new career.
This article was translated from Univadis Italy. A version appeared on Medscape.com.
COVID-19 imposed challenges on health care professionals and systems by forcing changes in how doctors organize themselves professionally as well as in their relationships with patients and in their expectations (realistic or not) of their roles. The situation was bound to generate high rates of frustration and discomfort among younger and older physicians. It was compounded by a generational transition of the profession, which was accelerated by the virus. It was not managed by the decision-makers and was painful for doctors and patients.
Impostor syndrome (IS) is a psychological construct characterized by the persistent belief that one’s success is undeserved, rather than stemming from personal effort, skill, and ability. The phenomenon is common among medics for various reasons, including professional burnout. Recent studies have helped to better define the extent and characteristic features of the syndrome, as well as efforts to combat it.
Doctors and burnout
Although occupational burnout among physicians is a systemic issue primarily attributable to problems in the practice environment, professional norms and aspects of medical culture often contribute to the distress that individual physicians experience.
These dimensions have been well characterized and include suggestions that physicians should be impervious to normal human limitations (that is, superhuman), that work should always come first, and that seeking help is a sign of weakness. In aggregate, these attitudes lead many physicians to engage in unhealthy levels of self-sacrifice, manifested by excessive work hours, anxiety about missing something that would benefit their patients, and prioritizing work over personal health. These factors are familiar to many hospital-based and family physicians.
The impostor phenomenon
The impostor phenomenon (IP) is a psychological experience of intellectual and professional fraud. Individuals who suffer from it believe that others have inflated perceptions of the individual’s abilities and fear being judged. This fear persists despite continual proof of the individual’s successes. These people ignore praise, are highly self-critical, and attribute their successes to external factors, such as luck, hard work, or receiving help from others, rather than to qualities such as skill, intelligence, or ability.
IP is common among men and women. Some studies suggest it may be more prevalent among women. Studies across industries suggest that the phenomenon is associated with personal consequences (for example, low emotional well-being, problems with work-life integration, anxiety, depression, suicide) and professional consequences (for example, impaired job performance, occupational burnout). Studies involving U.S. medical students have revealed that more than one in four medical students experience IP and that those who experience it are at higher risk for burnout.
Surveying IS
IS, which is not a formal psychiatric diagnosis, is defined as having feelings of uncertainty, inadequacy, and being undeserving of one’s achievements despite evidence to the contrary. There are five subtypes of IS:
- Perfectionist: insecurity related to self-imposed, unachievable goals
- Expert: feeling inadequate from lacking sufficient knowledge
- Superperson: assuming excessive workloads just to feel okay among peers
- Natural genius: experiencing shame when it takes effort to develop a skill
- Soloist: believing that requesting help is a sign of weakness
Risk factors
Studies suggest that IS is a problem early in the physician training process. There is limited information on IS among physicians in practice.
Because transitions represent a risk factor for IP, the frequent rotation between clerkships and being a “perpetual novice” during medical school training may contribute to the high prevalence. Qualitative studies suggest that, once in practice, other professional experiences (for example, unfavorable patient outcomes, patient complaints, rejection of grants or manuscripts, and poor teaching evaluations or patient satisfaction scores) may contribute to IP.
Impact on doctors
Several methods have been used to classify how much the phenomenon interferes with a person’s life. The Clance Impostor Phenomenon Scale is a 20-item scale that asks respondents to indicate how well each item characterizes their experience on a 5-point scale. Options range from “not at all” to “very true.” The sum of responses to the individual items is used to create an aggregate score (IP score). The higher the score, the more frequently and seriously IP interferes with a person’s life.
A simplified version of the IP score was used in a study of 3,237 U.S. doctors that investigated the association between IS and burnout among doctors and to compare their rates of IS with those of other professionals.
Mean IP scores were higher for female physicians than for male physicians (mean, 10.91 vs. 9.12; P < .001). Scores decreased with age and were lower among those who were married or widowed.
With respect to professional characteristics, IP scores were greater among those in academic practice or who worked in the Veterans Affairs medical system and decreased with years in practice.
The highest IP scores were among pediatric subspecialists, general pediatricians, and emergency medicine physicians. Scores were lowest among ophthalmologists, radiologists, and orthopedic surgeons. IP has been independently associated with the risk of burnout and low professional fulfillment.
Lessening the impact
An article commenting on the study highlighted the following expert practice strategies that doctors can use to reduce the impact of IS in their professional life.
- Review and celebrate feats that have led to your professional role.
- Share concerns with trusted colleagues who can validate your accomplishments and normalize your feelings by reporting their own struggles with IS.
- Combat perfectionism by accepting that it is okay to be good enough when meeting the challenges of a demanding profession.
- Exercise self-compassion as an alternative to relying on an external locus of self-worth.
- Understand that IS may be common, especially during transitions, such as when entering medical school, graduate medical training, or starting a new career.
This article was translated from Univadis Italy. A version appeared on Medscape.com.
COVID-19 imposed challenges on health care professionals and systems by forcing changes in how doctors organize themselves professionally as well as in their relationships with patients and in their expectations (realistic or not) of their roles. The situation was bound to generate high rates of frustration and discomfort among younger and older physicians. It was compounded by a generational transition of the profession, which was accelerated by the virus. It was not managed by the decision-makers and was painful for doctors and patients.
Impostor syndrome (IS) is a psychological construct characterized by the persistent belief that one’s success is undeserved, rather than stemming from personal effort, skill, and ability. The phenomenon is common among medics for various reasons, including professional burnout. Recent studies have helped to better define the extent and characteristic features of the syndrome, as well as efforts to combat it.
Doctors and burnout
Although occupational burnout among physicians is a systemic issue primarily attributable to problems in the practice environment, professional norms and aspects of medical culture often contribute to the distress that individual physicians experience.
These dimensions have been well characterized and include suggestions that physicians should be impervious to normal human limitations (that is, superhuman), that work should always come first, and that seeking help is a sign of weakness. In aggregate, these attitudes lead many physicians to engage in unhealthy levels of self-sacrifice, manifested by excessive work hours, anxiety about missing something that would benefit their patients, and prioritizing work over personal health. These factors are familiar to many hospital-based and family physicians.
The impostor phenomenon
The impostor phenomenon (IP) is a psychological experience of intellectual and professional fraud. Individuals who suffer from it believe that others have inflated perceptions of the individual’s abilities and fear being judged. This fear persists despite continual proof of the individual’s successes. These people ignore praise, are highly self-critical, and attribute their successes to external factors, such as luck, hard work, or receiving help from others, rather than to qualities such as skill, intelligence, or ability.
IP is common among men and women. Some studies suggest it may be more prevalent among women. Studies across industries suggest that the phenomenon is associated with personal consequences (for example, low emotional well-being, problems with work-life integration, anxiety, depression, suicide) and professional consequences (for example, impaired job performance, occupational burnout). Studies involving U.S. medical students have revealed that more than one in four medical students experience IP and that those who experience it are at higher risk for burnout.
Surveying IS
IS, which is not a formal psychiatric diagnosis, is defined as having feelings of uncertainty, inadequacy, and being undeserving of one’s achievements despite evidence to the contrary. There are five subtypes of IS:
- Perfectionist: insecurity related to self-imposed, unachievable goals
- Expert: feeling inadequate from lacking sufficient knowledge
- Superperson: assuming excessive workloads just to feel okay among peers
- Natural genius: experiencing shame when it takes effort to develop a skill
- Soloist: believing that requesting help is a sign of weakness
Risk factors
Studies suggest that IS is a problem early in the physician training process. There is limited information on IS among physicians in practice.
Because transitions represent a risk factor for IP, the frequent rotation between clerkships and being a “perpetual novice” during medical school training may contribute to the high prevalence. Qualitative studies suggest that, once in practice, other professional experiences (for example, unfavorable patient outcomes, patient complaints, rejection of grants or manuscripts, and poor teaching evaluations or patient satisfaction scores) may contribute to IP.
Impact on doctors
Several methods have been used to classify how much the phenomenon interferes with a person’s life. The Clance Impostor Phenomenon Scale is a 20-item scale that asks respondents to indicate how well each item characterizes their experience on a 5-point scale. Options range from “not at all” to “very true.” The sum of responses to the individual items is used to create an aggregate score (IP score). The higher the score, the more frequently and seriously IP interferes with a person’s life.
A simplified version of the IP score was used in a study of 3,237 U.S. doctors that investigated the association between IS and burnout among doctors and to compare their rates of IS with those of other professionals.
Mean IP scores were higher for female physicians than for male physicians (mean, 10.91 vs. 9.12; P < .001). Scores decreased with age and were lower among those who were married or widowed.
With respect to professional characteristics, IP scores were greater among those in academic practice or who worked in the Veterans Affairs medical system and decreased with years in practice.
The highest IP scores were among pediatric subspecialists, general pediatricians, and emergency medicine physicians. Scores were lowest among ophthalmologists, radiologists, and orthopedic surgeons. IP has been independently associated with the risk of burnout and low professional fulfillment.
Lessening the impact
An article commenting on the study highlighted the following expert practice strategies that doctors can use to reduce the impact of IS in their professional life.
- Review and celebrate feats that have led to your professional role.
- Share concerns with trusted colleagues who can validate your accomplishments and normalize your feelings by reporting their own struggles with IS.
- Combat perfectionism by accepting that it is okay to be good enough when meeting the challenges of a demanding profession.
- Exercise self-compassion as an alternative to relying on an external locus of self-worth.
- Understand that IS may be common, especially during transitions, such as when entering medical school, graduate medical training, or starting a new career.
This article was translated from Univadis Italy. A version appeared on Medscape.com.
Brisk walking: No-cost option for patients to improve cancer outcomes
This transcript has been edited for clarity.
I’m Maurie Markman, MD, from Cancer Treatment Centers of America in Philadelphia. I wanted to discuss a highly provocative paper that I think deserves attention. It was published in the Journal of Clinical Oncology, titled Physical Activity in Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).
This is an incredibly important paper that highlights something that has not been emphasized enough in oncology practice. What are the things that we can recommend to our patients that are not expensive, but which they can do for themselves to impact a potential for adding to a positive outcome? In this case, we’re talking about physical activity.
This was an extremely well-conducted study. It was a prospective cohort study that was built into an ongoing phase 3 randomized, multicenter study looking at adjuvant therapy of stage III colon cancer. The median follow-up in this population was almost 6 years. We’re talking about 1,696 patients.
The investigators did a survey, asking patients when they started treatment and then a short time after that, and measured the level of recreational physical activity. They didn’t do a design. They asked the individuals how much activity they had.
There were a number of analyses done in terms of looking at this that were reported in the paper. I want to highlight one because it’s so simple. The investigators looked at brisk walking. For brisk walking, the 3-year disease-free survival was 81.7% for individuals who had less than 1 hour per week of brisk walking versus 88.4% for individuals who walked briskly more than 3 hours per week.
There is no additional expense. It’s walking. There were other activities that were looked at here, including aerobic activities.
The bottom line is that physical activity is positive, is not expensive, and focuses on what the individual patient can do for themselves. It’s something I believe that, in the oncology community, we need to emphasize more.
I encourage you to review this paper and use your own opinion as to what you want to do with this information, but I strongly urge you to look at this – and other types of activities – that we can recommend that individuals do themselves to impact their outcomes related to cancer.
Dr. Markman is a clinical professor of medicine at Drexel University, Philadelphia. He reported conflicts of interest with Genentech, AstraZeneca, Celgene, Clovis, and Amgen.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I’m Maurie Markman, MD, from Cancer Treatment Centers of America in Philadelphia. I wanted to discuss a highly provocative paper that I think deserves attention. It was published in the Journal of Clinical Oncology, titled Physical Activity in Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).
This is an incredibly important paper that highlights something that has not been emphasized enough in oncology practice. What are the things that we can recommend to our patients that are not expensive, but which they can do for themselves to impact a potential for adding to a positive outcome? In this case, we’re talking about physical activity.
This was an extremely well-conducted study. It was a prospective cohort study that was built into an ongoing phase 3 randomized, multicenter study looking at adjuvant therapy of stage III colon cancer. The median follow-up in this population was almost 6 years. We’re talking about 1,696 patients.
The investigators did a survey, asking patients when they started treatment and then a short time after that, and measured the level of recreational physical activity. They didn’t do a design. They asked the individuals how much activity they had.
There were a number of analyses done in terms of looking at this that were reported in the paper. I want to highlight one because it’s so simple. The investigators looked at brisk walking. For brisk walking, the 3-year disease-free survival was 81.7% for individuals who had less than 1 hour per week of brisk walking versus 88.4% for individuals who walked briskly more than 3 hours per week.
There is no additional expense. It’s walking. There were other activities that were looked at here, including aerobic activities.
The bottom line is that physical activity is positive, is not expensive, and focuses on what the individual patient can do for themselves. It’s something I believe that, in the oncology community, we need to emphasize more.
I encourage you to review this paper and use your own opinion as to what you want to do with this information, but I strongly urge you to look at this – and other types of activities – that we can recommend that individuals do themselves to impact their outcomes related to cancer.
Dr. Markman is a clinical professor of medicine at Drexel University, Philadelphia. He reported conflicts of interest with Genentech, AstraZeneca, Celgene, Clovis, and Amgen.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I’m Maurie Markman, MD, from Cancer Treatment Centers of America in Philadelphia. I wanted to discuss a highly provocative paper that I think deserves attention. It was published in the Journal of Clinical Oncology, titled Physical Activity in Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).
This is an incredibly important paper that highlights something that has not been emphasized enough in oncology practice. What are the things that we can recommend to our patients that are not expensive, but which they can do for themselves to impact a potential for adding to a positive outcome? In this case, we’re talking about physical activity.
This was an extremely well-conducted study. It was a prospective cohort study that was built into an ongoing phase 3 randomized, multicenter study looking at adjuvant therapy of stage III colon cancer. The median follow-up in this population was almost 6 years. We’re talking about 1,696 patients.
The investigators did a survey, asking patients when they started treatment and then a short time after that, and measured the level of recreational physical activity. They didn’t do a design. They asked the individuals how much activity they had.
There were a number of analyses done in terms of looking at this that were reported in the paper. I want to highlight one because it’s so simple. The investigators looked at brisk walking. For brisk walking, the 3-year disease-free survival was 81.7% for individuals who had less than 1 hour per week of brisk walking versus 88.4% for individuals who walked briskly more than 3 hours per week.
There is no additional expense. It’s walking. There were other activities that were looked at here, including aerobic activities.
The bottom line is that physical activity is positive, is not expensive, and focuses on what the individual patient can do for themselves. It’s something I believe that, in the oncology community, we need to emphasize more.
I encourage you to review this paper and use your own opinion as to what you want to do with this information, but I strongly urge you to look at this – and other types of activities – that we can recommend that individuals do themselves to impact their outcomes related to cancer.
Dr. Markman is a clinical professor of medicine at Drexel University, Philadelphia. He reported conflicts of interest with Genentech, AstraZeneca, Celgene, Clovis, and Amgen.
A version of this article first appeared on Medscape.com.
Has the time come to bury BMI in favor of other screening measures?
In 1832, Belgian statistician Adolphe Quetelet introduced the concept of body mass index (BMI) – one’s weight (in kilograms) divided by the square of one’s height (in meters) as a measurement of ideal body weight. Approximately 140 years later, nutritional epidemiologist Ancel Keys proposed the use of BMI as a surrogate marker for evaluating body fat percentage within a population.
For the past 50 years, the scientific and medical communities have relied on BMI as a research and study tool to categorize patients’ weight (that is, severely underweight, underweight, normal weight, overweight, and obesity). The World Health Organization, National Institutes of Health, and U.S. Centers for Disease Control and Prevention use the following BMI weight classifications for adult patients:
- Underweight: BMI < 18.5
- Normal weight: BMI ≥ 18.5 to 24.9
- Overweight: BMI ≥ 25 to 29.9
- Obesity: BMI ≥ 30
Of note, BMI categories for children and adolescents (aged 2-19 years) are based on sex- and age-specific percentiles and will not be addressed in this article.
BMI appears to be a straightforward, easy, and cost-effective way to identify “healthy” weight and assess a patient’s risk for related conditions. For example, studies show that a BMI ≥ 35 kg/m2 correlates to higher prevalence of type 2 diabetes, hypertension, dyslipidemia, and decreased lifespan. At least 13 types of cancer have been linked to obesity, regardless of dietary or physical activity behaviors. While the health dangers associated with BMI ≥ 35 are substantial and difficult to dispute, concerns arise when BMI alone is used to determine healthy weight and disease risk in patients with a BMI of 25-35.
BMI limitations
There are troubling limitations to using BMI alone to assess a patient’s weight and health status. BMI only takes into account a patient’s height and weight, neither of which are sole determinants of health. Moreover, BMI measurements do not distinguish between fat mass and fat-free mass, each of which has very distinct effects on health. High fat mass is associated with an increased risk for disease and mortality, while higher lean body mass correlates with increased physical fitness and longevity. BMI also does not consider age, sex, race, ethnicity, or types of adipose tissue, all of which tremendously influence disease risk across all BMI categories.
Body composition and adipose tissue
Body composition and type of excess adipose tissue better correlate disease risk than does BMI. The World Health Organization defines obesity as having a body fat percentage > 25% for men and > 35% for women. Body composition can be measured by skin-fold thickness, bioelectrical impedance, dual-energy x-ray absorptiometry (DXA), CT, or MRI.
A cross-sectional study by Shah and colleagues) comparing BMI and DXA found that BMI underestimated obesity prevalence. In the study, BMI characterized 26% of participants as obese while DXA (a direct measurement of fat) characterized 64%. Further, 39% of patients categorized as nonobese based on BMI were found to be obese on DXA. Also, BMI misclassified 25% of men and 48% of women in the study. These findings and those of other studies suggest that BMI has a high specificity but low sensitivity for diagnosing obesity, questioning its reliability as a clinical screening tool.
Current guideline recommendations on pharmacologic and surgical treatment options for patients with overweight or obesity, including those of the American Association of Clinical Endocrinology and American College of Endocrinology (AACE/ACE) and the American College of Cardiology/American Heart Association and The Obesity Society (ACC/AHA/TOS), rely on BMI, diminishing their utilization. For example, a recent literature search by Li and associates found that Asian American patients with lower BMIs and BMIs of 25 or 27 are at increased risk for metabolic disease. On the basis of study findings, some organizations recommend considering pharmacotherapy at a lower BMI cutoff of ≥ 25.0 or ≥ 27.5 for Asian people to ensure early treatment intervention in this patient population because guidelines do not recommend pharmacologic treatment unless the BMI is 27 with weight-related complications or 30. Under the current guidelines, a patient of Asian descent has greater disease severity with potentially more complications by the time pharmacotherapy is initiated.
As previously noted, body composition, which requires the use of special equipment (skinfold calipers, DXA, CT, MRI, body impedance scale), best captures the ratio of fat mass to fat-free mass. DXA is frequently used in research studies looking at body composition because of its lower cost, faster time to obtain the study, and ability to measure bone density. MRI has been found to be as accurate as CT for assessing visceral adipose tissue (VAT), skeletal muscle mass, and organ mass, and does not expose patients to ionizing radiation like CT does. MRI clinical use, however, is limited because of its high cost, and it may be problematic for patients with claustrophobia or who are unable to remain immobile for an extended period.
Patients with a high VAT mass, compared with subcutaneous adipose tissue (SAT), are at increased risk for metabolic syndrome, nonalcoholic fatty liver disease, and cardiovascular disease regardless of BMI, underscoring the clinical usefulness of measuring visceral adiposity over BMI.
One of the barriers to implementing VAT assessment in clinical practice is the cost of imaging studies. Fortunately, data suggest that waist circumference and/or waist-to-hip ratio measurements can be a valuable surrogate for VAT measurement. A waist circumference greater than 35 inches (88 cm) or a waist-to-hip ratio greater than 0.8 for women, and greater than 40 inches (102 cm) or a waist-to-hip ratio greater than 0.95 for men, increases metabolic disease risk. Obtaining these measurements requires a tape measure and a few extra minutes and offers more potent data than BMI alone. For example, a large cardiometabolic study found that within each BMI category, increasing gender-specific waist circumferences were associated with significantly higher VAT, liver fat, and a more harmful cardiometabolic risk profile. Men and women with a lower or normal BMI and a high waist circumference are at greatest relative health risk, compared with those with low waist circumference values. Yet, using the BMI alone in these patients would not raise any clinical concern, which is a missed opportunity for cardiometabolic risk reduction.
Biomarkers
Specific biomarkers are closely related to obesity. Leptin and resistin protein levels increase with adipose mass, while adiponectin decreases, probably contributing to insulin resistance. The higher levels of tumor necrosis factor–alpha and interleukin-6 from obesity contribute to chronic inflammation. The combined effect of chronic inflammation and insulin resistance allows greater bioavailability of insulinlike growth factor-1 (IGF-1), which has a role in initiating type 2 diabetes, cardiovascular disease, and cancer. Ideally, measuring these biomarkers could provide more advantageous information than BMI. Unfortunately, for now, the lack of standardized assays and imperfect knowledge of exactly how these biomarkers elicit disease prevents clinical use.
Obesity is a common, highly complex, chronic, and relapsing disease. Thankfully, a number of effective treatments and interventions are available. Although an accurate diagnosis of obesity is essential, underdiagnosed cases and missed opportunities for metabolic disease risk reduction persist. Overdiagnosing obesity, however, has the potential to incur unnecessary health care costs and result in weight bias and stigma.
While BMI is a quick and inexpensive means to assess obesity, by itself it lacks the necessary components for an accurate diagnosis. Particularly for individuals with a normal BMI or less severe overweight/obesity (BMI 27-34.9), other factors must be accounted for, including age, gender, and race. At a minimum, waist circumference should be measured to best risk-stratify and determine treatment intensity. Body composition analysis with BMI calculation refines the diagnosis of obesity.
Finally, clinicians may find best practices by using BMI delta change models. As with so many other clinical measurements, the trajectory tells the most astute story. For example, a patient whose BMI decreased from 45 to 35 may warrant less intensive treatment than a patient whose BMI increased from 26 to 31. Any change in BMI warrants clinical attention. A rapidly or consistently increasing BMI, even within normal range, should prompt clinicians to assess other factors related to obesity and metabolic disease risk (for example, lifestyle factors, waist circumference, blood pressure, cholesterol, diabetes screening) and initiate a conversation about weight management. Similarly, a consistently or rapidly decreasing BMI – even in elevated ranges and particularly with unintentional weight loss – should prompt evaluation.
Although BMI continues to be useful in clinical practice, epidemiology, and research, it should be used in combination with other clinical factors to provide the utmost quality of care.
Dr. Bartfield is assistant professor, obesity medicine specialist, Wake Forest Baptists Medical Center/Atrium Health Weight Management Center, Greensboro, N.C. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
In 1832, Belgian statistician Adolphe Quetelet introduced the concept of body mass index (BMI) – one’s weight (in kilograms) divided by the square of one’s height (in meters) as a measurement of ideal body weight. Approximately 140 years later, nutritional epidemiologist Ancel Keys proposed the use of BMI as a surrogate marker for evaluating body fat percentage within a population.
For the past 50 years, the scientific and medical communities have relied on BMI as a research and study tool to categorize patients’ weight (that is, severely underweight, underweight, normal weight, overweight, and obesity). The World Health Organization, National Institutes of Health, and U.S. Centers for Disease Control and Prevention use the following BMI weight classifications for adult patients:
- Underweight: BMI < 18.5
- Normal weight: BMI ≥ 18.5 to 24.9
- Overweight: BMI ≥ 25 to 29.9
- Obesity: BMI ≥ 30
Of note, BMI categories for children and adolescents (aged 2-19 years) are based on sex- and age-specific percentiles and will not be addressed in this article.
BMI appears to be a straightforward, easy, and cost-effective way to identify “healthy” weight and assess a patient’s risk for related conditions. For example, studies show that a BMI ≥ 35 kg/m2 correlates to higher prevalence of type 2 diabetes, hypertension, dyslipidemia, and decreased lifespan. At least 13 types of cancer have been linked to obesity, regardless of dietary or physical activity behaviors. While the health dangers associated with BMI ≥ 35 are substantial and difficult to dispute, concerns arise when BMI alone is used to determine healthy weight and disease risk in patients with a BMI of 25-35.
BMI limitations
There are troubling limitations to using BMI alone to assess a patient’s weight and health status. BMI only takes into account a patient’s height and weight, neither of which are sole determinants of health. Moreover, BMI measurements do not distinguish between fat mass and fat-free mass, each of which has very distinct effects on health. High fat mass is associated with an increased risk for disease and mortality, while higher lean body mass correlates with increased physical fitness and longevity. BMI also does not consider age, sex, race, ethnicity, or types of adipose tissue, all of which tremendously influence disease risk across all BMI categories.
Body composition and adipose tissue
Body composition and type of excess adipose tissue better correlate disease risk than does BMI. The World Health Organization defines obesity as having a body fat percentage > 25% for men and > 35% for women. Body composition can be measured by skin-fold thickness, bioelectrical impedance, dual-energy x-ray absorptiometry (DXA), CT, or MRI.
A cross-sectional study by Shah and colleagues) comparing BMI and DXA found that BMI underestimated obesity prevalence. In the study, BMI characterized 26% of participants as obese while DXA (a direct measurement of fat) characterized 64%. Further, 39% of patients categorized as nonobese based on BMI were found to be obese on DXA. Also, BMI misclassified 25% of men and 48% of women in the study. These findings and those of other studies suggest that BMI has a high specificity but low sensitivity for diagnosing obesity, questioning its reliability as a clinical screening tool.
Current guideline recommendations on pharmacologic and surgical treatment options for patients with overweight or obesity, including those of the American Association of Clinical Endocrinology and American College of Endocrinology (AACE/ACE) and the American College of Cardiology/American Heart Association and The Obesity Society (ACC/AHA/TOS), rely on BMI, diminishing their utilization. For example, a recent literature search by Li and associates found that Asian American patients with lower BMIs and BMIs of 25 or 27 are at increased risk for metabolic disease. On the basis of study findings, some organizations recommend considering pharmacotherapy at a lower BMI cutoff of ≥ 25.0 or ≥ 27.5 for Asian people to ensure early treatment intervention in this patient population because guidelines do not recommend pharmacologic treatment unless the BMI is 27 with weight-related complications or 30. Under the current guidelines, a patient of Asian descent has greater disease severity with potentially more complications by the time pharmacotherapy is initiated.
As previously noted, body composition, which requires the use of special equipment (skinfold calipers, DXA, CT, MRI, body impedance scale), best captures the ratio of fat mass to fat-free mass. DXA is frequently used in research studies looking at body composition because of its lower cost, faster time to obtain the study, and ability to measure bone density. MRI has been found to be as accurate as CT for assessing visceral adipose tissue (VAT), skeletal muscle mass, and organ mass, and does not expose patients to ionizing radiation like CT does. MRI clinical use, however, is limited because of its high cost, and it may be problematic for patients with claustrophobia or who are unable to remain immobile for an extended period.
Patients with a high VAT mass, compared with subcutaneous adipose tissue (SAT), are at increased risk for metabolic syndrome, nonalcoholic fatty liver disease, and cardiovascular disease regardless of BMI, underscoring the clinical usefulness of measuring visceral adiposity over BMI.
One of the barriers to implementing VAT assessment in clinical practice is the cost of imaging studies. Fortunately, data suggest that waist circumference and/or waist-to-hip ratio measurements can be a valuable surrogate for VAT measurement. A waist circumference greater than 35 inches (88 cm) or a waist-to-hip ratio greater than 0.8 for women, and greater than 40 inches (102 cm) or a waist-to-hip ratio greater than 0.95 for men, increases metabolic disease risk. Obtaining these measurements requires a tape measure and a few extra minutes and offers more potent data than BMI alone. For example, a large cardiometabolic study found that within each BMI category, increasing gender-specific waist circumferences were associated with significantly higher VAT, liver fat, and a more harmful cardiometabolic risk profile. Men and women with a lower or normal BMI and a high waist circumference are at greatest relative health risk, compared with those with low waist circumference values. Yet, using the BMI alone in these patients would not raise any clinical concern, which is a missed opportunity for cardiometabolic risk reduction.
Biomarkers
Specific biomarkers are closely related to obesity. Leptin and resistin protein levels increase with adipose mass, while adiponectin decreases, probably contributing to insulin resistance. The higher levels of tumor necrosis factor–alpha and interleukin-6 from obesity contribute to chronic inflammation. The combined effect of chronic inflammation and insulin resistance allows greater bioavailability of insulinlike growth factor-1 (IGF-1), which has a role in initiating type 2 diabetes, cardiovascular disease, and cancer. Ideally, measuring these biomarkers could provide more advantageous information than BMI. Unfortunately, for now, the lack of standardized assays and imperfect knowledge of exactly how these biomarkers elicit disease prevents clinical use.
Obesity is a common, highly complex, chronic, and relapsing disease. Thankfully, a number of effective treatments and interventions are available. Although an accurate diagnosis of obesity is essential, underdiagnosed cases and missed opportunities for metabolic disease risk reduction persist. Overdiagnosing obesity, however, has the potential to incur unnecessary health care costs and result in weight bias and stigma.
While BMI is a quick and inexpensive means to assess obesity, by itself it lacks the necessary components for an accurate diagnosis. Particularly for individuals with a normal BMI or less severe overweight/obesity (BMI 27-34.9), other factors must be accounted for, including age, gender, and race. At a minimum, waist circumference should be measured to best risk-stratify and determine treatment intensity. Body composition analysis with BMI calculation refines the diagnosis of obesity.
Finally, clinicians may find best practices by using BMI delta change models. As with so many other clinical measurements, the trajectory tells the most astute story. For example, a patient whose BMI decreased from 45 to 35 may warrant less intensive treatment than a patient whose BMI increased from 26 to 31. Any change in BMI warrants clinical attention. A rapidly or consistently increasing BMI, even within normal range, should prompt clinicians to assess other factors related to obesity and metabolic disease risk (for example, lifestyle factors, waist circumference, blood pressure, cholesterol, diabetes screening) and initiate a conversation about weight management. Similarly, a consistently or rapidly decreasing BMI – even in elevated ranges and particularly with unintentional weight loss – should prompt evaluation.
Although BMI continues to be useful in clinical practice, epidemiology, and research, it should be used in combination with other clinical factors to provide the utmost quality of care.
Dr. Bartfield is assistant professor, obesity medicine specialist, Wake Forest Baptists Medical Center/Atrium Health Weight Management Center, Greensboro, N.C. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
In 1832, Belgian statistician Adolphe Quetelet introduced the concept of body mass index (BMI) – one’s weight (in kilograms) divided by the square of one’s height (in meters) as a measurement of ideal body weight. Approximately 140 years later, nutritional epidemiologist Ancel Keys proposed the use of BMI as a surrogate marker for evaluating body fat percentage within a population.
For the past 50 years, the scientific and medical communities have relied on BMI as a research and study tool to categorize patients’ weight (that is, severely underweight, underweight, normal weight, overweight, and obesity). The World Health Organization, National Institutes of Health, and U.S. Centers for Disease Control and Prevention use the following BMI weight classifications for adult patients:
- Underweight: BMI < 18.5
- Normal weight: BMI ≥ 18.5 to 24.9
- Overweight: BMI ≥ 25 to 29.9
- Obesity: BMI ≥ 30
Of note, BMI categories for children and adolescents (aged 2-19 years) are based on sex- and age-specific percentiles and will not be addressed in this article.
BMI appears to be a straightforward, easy, and cost-effective way to identify “healthy” weight and assess a patient’s risk for related conditions. For example, studies show that a BMI ≥ 35 kg/m2 correlates to higher prevalence of type 2 diabetes, hypertension, dyslipidemia, and decreased lifespan. At least 13 types of cancer have been linked to obesity, regardless of dietary or physical activity behaviors. While the health dangers associated with BMI ≥ 35 are substantial and difficult to dispute, concerns arise when BMI alone is used to determine healthy weight and disease risk in patients with a BMI of 25-35.
BMI limitations
There are troubling limitations to using BMI alone to assess a patient’s weight and health status. BMI only takes into account a patient’s height and weight, neither of which are sole determinants of health. Moreover, BMI measurements do not distinguish between fat mass and fat-free mass, each of which has very distinct effects on health. High fat mass is associated with an increased risk for disease and mortality, while higher lean body mass correlates with increased physical fitness and longevity. BMI also does not consider age, sex, race, ethnicity, or types of adipose tissue, all of which tremendously influence disease risk across all BMI categories.
Body composition and adipose tissue
Body composition and type of excess adipose tissue better correlate disease risk than does BMI. The World Health Organization defines obesity as having a body fat percentage > 25% for men and > 35% for women. Body composition can be measured by skin-fold thickness, bioelectrical impedance, dual-energy x-ray absorptiometry (DXA), CT, or MRI.
A cross-sectional study by Shah and colleagues) comparing BMI and DXA found that BMI underestimated obesity prevalence. In the study, BMI characterized 26% of participants as obese while DXA (a direct measurement of fat) characterized 64%. Further, 39% of patients categorized as nonobese based on BMI were found to be obese on DXA. Also, BMI misclassified 25% of men and 48% of women in the study. These findings and those of other studies suggest that BMI has a high specificity but low sensitivity for diagnosing obesity, questioning its reliability as a clinical screening tool.
Current guideline recommendations on pharmacologic and surgical treatment options for patients with overweight or obesity, including those of the American Association of Clinical Endocrinology and American College of Endocrinology (AACE/ACE) and the American College of Cardiology/American Heart Association and The Obesity Society (ACC/AHA/TOS), rely on BMI, diminishing their utilization. For example, a recent literature search by Li and associates found that Asian American patients with lower BMIs and BMIs of 25 or 27 are at increased risk for metabolic disease. On the basis of study findings, some organizations recommend considering pharmacotherapy at a lower BMI cutoff of ≥ 25.0 or ≥ 27.5 for Asian people to ensure early treatment intervention in this patient population because guidelines do not recommend pharmacologic treatment unless the BMI is 27 with weight-related complications or 30. Under the current guidelines, a patient of Asian descent has greater disease severity with potentially more complications by the time pharmacotherapy is initiated.
As previously noted, body composition, which requires the use of special equipment (skinfold calipers, DXA, CT, MRI, body impedance scale), best captures the ratio of fat mass to fat-free mass. DXA is frequently used in research studies looking at body composition because of its lower cost, faster time to obtain the study, and ability to measure bone density. MRI has been found to be as accurate as CT for assessing visceral adipose tissue (VAT), skeletal muscle mass, and organ mass, and does not expose patients to ionizing radiation like CT does. MRI clinical use, however, is limited because of its high cost, and it may be problematic for patients with claustrophobia or who are unable to remain immobile for an extended period.
Patients with a high VAT mass, compared with subcutaneous adipose tissue (SAT), are at increased risk for metabolic syndrome, nonalcoholic fatty liver disease, and cardiovascular disease regardless of BMI, underscoring the clinical usefulness of measuring visceral adiposity over BMI.
One of the barriers to implementing VAT assessment in clinical practice is the cost of imaging studies. Fortunately, data suggest that waist circumference and/or waist-to-hip ratio measurements can be a valuable surrogate for VAT measurement. A waist circumference greater than 35 inches (88 cm) or a waist-to-hip ratio greater than 0.8 for women, and greater than 40 inches (102 cm) or a waist-to-hip ratio greater than 0.95 for men, increases metabolic disease risk. Obtaining these measurements requires a tape measure and a few extra minutes and offers more potent data than BMI alone. For example, a large cardiometabolic study found that within each BMI category, increasing gender-specific waist circumferences were associated with significantly higher VAT, liver fat, and a more harmful cardiometabolic risk profile. Men and women with a lower or normal BMI and a high waist circumference are at greatest relative health risk, compared with those with low waist circumference values. Yet, using the BMI alone in these patients would not raise any clinical concern, which is a missed opportunity for cardiometabolic risk reduction.
Biomarkers
Specific biomarkers are closely related to obesity. Leptin and resistin protein levels increase with adipose mass, while adiponectin decreases, probably contributing to insulin resistance. The higher levels of tumor necrosis factor–alpha and interleukin-6 from obesity contribute to chronic inflammation. The combined effect of chronic inflammation and insulin resistance allows greater bioavailability of insulinlike growth factor-1 (IGF-1), which has a role in initiating type 2 diabetes, cardiovascular disease, and cancer. Ideally, measuring these biomarkers could provide more advantageous information than BMI. Unfortunately, for now, the lack of standardized assays and imperfect knowledge of exactly how these biomarkers elicit disease prevents clinical use.
Obesity is a common, highly complex, chronic, and relapsing disease. Thankfully, a number of effective treatments and interventions are available. Although an accurate diagnosis of obesity is essential, underdiagnosed cases and missed opportunities for metabolic disease risk reduction persist. Overdiagnosing obesity, however, has the potential to incur unnecessary health care costs and result in weight bias and stigma.
While BMI is a quick and inexpensive means to assess obesity, by itself it lacks the necessary components for an accurate diagnosis. Particularly for individuals with a normal BMI or less severe overweight/obesity (BMI 27-34.9), other factors must be accounted for, including age, gender, and race. At a minimum, waist circumference should be measured to best risk-stratify and determine treatment intensity. Body composition analysis with BMI calculation refines the diagnosis of obesity.
Finally, clinicians may find best practices by using BMI delta change models. As with so many other clinical measurements, the trajectory tells the most astute story. For example, a patient whose BMI decreased from 45 to 35 may warrant less intensive treatment than a patient whose BMI increased from 26 to 31. Any change in BMI warrants clinical attention. A rapidly or consistently increasing BMI, even within normal range, should prompt clinicians to assess other factors related to obesity and metabolic disease risk (for example, lifestyle factors, waist circumference, blood pressure, cholesterol, diabetes screening) and initiate a conversation about weight management. Similarly, a consistently or rapidly decreasing BMI – even in elevated ranges and particularly with unintentional weight loss – should prompt evaluation.
Although BMI continues to be useful in clinical practice, epidemiology, and research, it should be used in combination with other clinical factors to provide the utmost quality of care.
Dr. Bartfield is assistant professor, obesity medicine specialist, Wake Forest Baptists Medical Center/Atrium Health Weight Management Center, Greensboro, N.C. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
One type of bariatric surgery betters IBD outcomes
Previous studies have shown that bariatric surgery is safe for people with IBD, but there have been few long-term data on whether the weight loss improves disease outcomes for that population, said lead author Aakash Desai, MD, from the division of gastroenterology and hepatology at Case Western Reserve University, Cleveland, in an interview.
Gastroenterologists are often hesitant to pursue bariatric surgery in patients with IBD because of potential complications from taking immunosuppressive medications, Dr. Desai added.
“We hope that this encourages providers caring for patients with IBD to make a referral to a weight loss specialist who can evaluate whether they would be candidates for bariatric surgery,” he said.
The findings from Dr. Desai and co-authors were published online in the Journal of Clinical Gastroenterology.
Outcomes compared with and without surgery
The prevalence of obesity in patients with IBD ranges from 15% to 40%, the authors note.
And although obesity is a risk factor for IBD disease severity and clinical outcomes, studies on its influence on disease outcomes in patients with IBD have reported conflicting results. The effect of bariatric surgery, an antiobesity intervention, on IBD outcomes also has not been well understood, the authors write.
To evaluate the effect of bariatric surgery on IBD, the researchers compared outcomes in patients living with IBD and morbid obesity who had bariatric surgery versus those in patients living with both conditions who had not had surgery. The retrospective, propensity score–matched cohort study used de-identified U.S. data on 473 patients and 473 controls from TriNetX, a diverse, population-based research network of health care organizations.
The primary endpoint was a composite of disease-related complications. The composite included a disease flare that resulted in hospitalization requiring an intravenous steroid or major IBD-related surgery within 2 years.
Researchers found that the surgery group had a lower risk (adjusted odds ratio, 0.31; 95% confidence interval, 0.17-0.56) for a composite of IBD-related complications, compared with controls.
Looking at the impact of bariatric surgery type, they found that patients who had a sleeve gastrectomy had a decreased risk (aOR, 0.45; 95% CI, 0.31-0.66) for the composite of IBD-related complications. There was no significant difference in the risk (aOR, 0.77; 95% CI, 0.45-1.31) for composite IBD-related complications between the Roux-en-Y gastric bypass group and controls.
As to why sleeve gastrectomy can improve outcomes with IBD, the authors write that “studies have shown a decrease in the low chronic pro-inflammatory state associated with obesity with reductions in C-reactive protein, TNF-α, and IL-6 following weight loss after [bariatric surgery].”
The authors add that another reason could be that the decrease from surgery in adipose tissue hypertrophy and ectopic fat around the bowel may help regulate intestinal inflammation in Crohn’s disease and “may affect the need for rescue therapy with intravenous steroids, failure/escalation of therapy, and risk of surgery.”
Study helps confirm benefits of weight loss
Ali Aminian, MD, director of the Bariatric and Metabolic Institute at the Cleveland Clinic, said this study furthers understanding because it used a large national database and helps confirm findings from smaller cohorts regarding the benefit of large weight loss for patients with IBD.
“Obesity can worsen the severity of inflammatory conditions,” he said in an interview, so it can be hard for gastroenterologists to help patients with obesity to control their IBD symptoms. Dr. Aminian has previously published research on the relationship between IBD and obesity.
“Telling the patient to eat less or exercise probably won’t help,” he said, adding that this study helps make the case for either bariatric surgery or new weight loss medications that have demonstrated significant effect.
Dr. Aminian said this study showed a dramatic benefit after bariatric surgery for IBD patients, but some questions need further study.
“Ideally, we need to have prospective clinical trials with a good control group and accurate endoscopy findings” to get a true long-term picture of the weight loss effect on IBD, he said.
Dr. Desai reports no relevant financial relationships. Co-author Farraye serves on advisory boards for Braintree, BMS, GI Reviewers, GSK, IBD Educational Group, Iterative Health, Janssen, Pfizer, and Sebela and is on the data safety monitoring board for Adiso Therapeutics. Co-author Kochhar serves on the advisory boards for Lilly Pharmaceuticals, CorEvitas Research Foundation, and GIE Medical and has stock options with Digbi Health. Aminian receives research support and speaking honoraria from Medtronic and Ethicon.
A version of this article appeared on Medscape.com.
Previous studies have shown that bariatric surgery is safe for people with IBD, but there have been few long-term data on whether the weight loss improves disease outcomes for that population, said lead author Aakash Desai, MD, from the division of gastroenterology and hepatology at Case Western Reserve University, Cleveland, in an interview.
Gastroenterologists are often hesitant to pursue bariatric surgery in patients with IBD because of potential complications from taking immunosuppressive medications, Dr. Desai added.
“We hope that this encourages providers caring for patients with IBD to make a referral to a weight loss specialist who can evaluate whether they would be candidates for bariatric surgery,” he said.
The findings from Dr. Desai and co-authors were published online in the Journal of Clinical Gastroenterology.
Outcomes compared with and without surgery
The prevalence of obesity in patients with IBD ranges from 15% to 40%, the authors note.
And although obesity is a risk factor for IBD disease severity and clinical outcomes, studies on its influence on disease outcomes in patients with IBD have reported conflicting results. The effect of bariatric surgery, an antiobesity intervention, on IBD outcomes also has not been well understood, the authors write.
To evaluate the effect of bariatric surgery on IBD, the researchers compared outcomes in patients living with IBD and morbid obesity who had bariatric surgery versus those in patients living with both conditions who had not had surgery. The retrospective, propensity score–matched cohort study used de-identified U.S. data on 473 patients and 473 controls from TriNetX, a diverse, population-based research network of health care organizations.
The primary endpoint was a composite of disease-related complications. The composite included a disease flare that resulted in hospitalization requiring an intravenous steroid or major IBD-related surgery within 2 years.
Researchers found that the surgery group had a lower risk (adjusted odds ratio, 0.31; 95% confidence interval, 0.17-0.56) for a composite of IBD-related complications, compared with controls.
Looking at the impact of bariatric surgery type, they found that patients who had a sleeve gastrectomy had a decreased risk (aOR, 0.45; 95% CI, 0.31-0.66) for the composite of IBD-related complications. There was no significant difference in the risk (aOR, 0.77; 95% CI, 0.45-1.31) for composite IBD-related complications between the Roux-en-Y gastric bypass group and controls.
As to why sleeve gastrectomy can improve outcomes with IBD, the authors write that “studies have shown a decrease in the low chronic pro-inflammatory state associated with obesity with reductions in C-reactive protein, TNF-α, and IL-6 following weight loss after [bariatric surgery].”
The authors add that another reason could be that the decrease from surgery in adipose tissue hypertrophy and ectopic fat around the bowel may help regulate intestinal inflammation in Crohn’s disease and “may affect the need for rescue therapy with intravenous steroids, failure/escalation of therapy, and risk of surgery.”
Study helps confirm benefits of weight loss
Ali Aminian, MD, director of the Bariatric and Metabolic Institute at the Cleveland Clinic, said this study furthers understanding because it used a large national database and helps confirm findings from smaller cohorts regarding the benefit of large weight loss for patients with IBD.
“Obesity can worsen the severity of inflammatory conditions,” he said in an interview, so it can be hard for gastroenterologists to help patients with obesity to control their IBD symptoms. Dr. Aminian has previously published research on the relationship between IBD and obesity.
“Telling the patient to eat less or exercise probably won’t help,” he said, adding that this study helps make the case for either bariatric surgery or new weight loss medications that have demonstrated significant effect.
Dr. Aminian said this study showed a dramatic benefit after bariatric surgery for IBD patients, but some questions need further study.
“Ideally, we need to have prospective clinical trials with a good control group and accurate endoscopy findings” to get a true long-term picture of the weight loss effect on IBD, he said.
Dr. Desai reports no relevant financial relationships. Co-author Farraye serves on advisory boards for Braintree, BMS, GI Reviewers, GSK, IBD Educational Group, Iterative Health, Janssen, Pfizer, and Sebela and is on the data safety monitoring board for Adiso Therapeutics. Co-author Kochhar serves on the advisory boards for Lilly Pharmaceuticals, CorEvitas Research Foundation, and GIE Medical and has stock options with Digbi Health. Aminian receives research support and speaking honoraria from Medtronic and Ethicon.
A version of this article appeared on Medscape.com.
Previous studies have shown that bariatric surgery is safe for people with IBD, but there have been few long-term data on whether the weight loss improves disease outcomes for that population, said lead author Aakash Desai, MD, from the division of gastroenterology and hepatology at Case Western Reserve University, Cleveland, in an interview.
Gastroenterologists are often hesitant to pursue bariatric surgery in patients with IBD because of potential complications from taking immunosuppressive medications, Dr. Desai added.
“We hope that this encourages providers caring for patients with IBD to make a referral to a weight loss specialist who can evaluate whether they would be candidates for bariatric surgery,” he said.
The findings from Dr. Desai and co-authors were published online in the Journal of Clinical Gastroenterology.
Outcomes compared with and without surgery
The prevalence of obesity in patients with IBD ranges from 15% to 40%, the authors note.
And although obesity is a risk factor for IBD disease severity and clinical outcomes, studies on its influence on disease outcomes in patients with IBD have reported conflicting results. The effect of bariatric surgery, an antiobesity intervention, on IBD outcomes also has not been well understood, the authors write.
To evaluate the effect of bariatric surgery on IBD, the researchers compared outcomes in patients living with IBD and morbid obesity who had bariatric surgery versus those in patients living with both conditions who had not had surgery. The retrospective, propensity score–matched cohort study used de-identified U.S. data on 473 patients and 473 controls from TriNetX, a diverse, population-based research network of health care organizations.
The primary endpoint was a composite of disease-related complications. The composite included a disease flare that resulted in hospitalization requiring an intravenous steroid or major IBD-related surgery within 2 years.
Researchers found that the surgery group had a lower risk (adjusted odds ratio, 0.31; 95% confidence interval, 0.17-0.56) for a composite of IBD-related complications, compared with controls.
Looking at the impact of bariatric surgery type, they found that patients who had a sleeve gastrectomy had a decreased risk (aOR, 0.45; 95% CI, 0.31-0.66) for the composite of IBD-related complications. There was no significant difference in the risk (aOR, 0.77; 95% CI, 0.45-1.31) for composite IBD-related complications between the Roux-en-Y gastric bypass group and controls.
As to why sleeve gastrectomy can improve outcomes with IBD, the authors write that “studies have shown a decrease in the low chronic pro-inflammatory state associated with obesity with reductions in C-reactive protein, TNF-α, and IL-6 following weight loss after [bariatric surgery].”
The authors add that another reason could be that the decrease from surgery in adipose tissue hypertrophy and ectopic fat around the bowel may help regulate intestinal inflammation in Crohn’s disease and “may affect the need for rescue therapy with intravenous steroids, failure/escalation of therapy, and risk of surgery.”
Study helps confirm benefits of weight loss
Ali Aminian, MD, director of the Bariatric and Metabolic Institute at the Cleveland Clinic, said this study furthers understanding because it used a large national database and helps confirm findings from smaller cohorts regarding the benefit of large weight loss for patients with IBD.
“Obesity can worsen the severity of inflammatory conditions,” he said in an interview, so it can be hard for gastroenterologists to help patients with obesity to control their IBD symptoms. Dr. Aminian has previously published research on the relationship between IBD and obesity.
“Telling the patient to eat less or exercise probably won’t help,” he said, adding that this study helps make the case for either bariatric surgery or new weight loss medications that have demonstrated significant effect.
Dr. Aminian said this study showed a dramatic benefit after bariatric surgery for IBD patients, but some questions need further study.
“Ideally, we need to have prospective clinical trials with a good control group and accurate endoscopy findings” to get a true long-term picture of the weight loss effect on IBD, he said.
Dr. Desai reports no relevant financial relationships. Co-author Farraye serves on advisory boards for Braintree, BMS, GI Reviewers, GSK, IBD Educational Group, Iterative Health, Janssen, Pfizer, and Sebela and is on the data safety monitoring board for Adiso Therapeutics. Co-author Kochhar serves on the advisory boards for Lilly Pharmaceuticals, CorEvitas Research Foundation, and GIE Medical and has stock options with Digbi Health. Aminian receives research support and speaking honoraria from Medtronic and Ethicon.
A version of this article appeared on Medscape.com.
FROM JOURNAL OF CLINICAL GASTROENTEROLOGY