User login
Artificial sweeteners no help for weight loss: Review
It also shows evidence that these products are not beneficial for controlling excess weight.
Francisco Gómez-Delgado, MD, PhD, and Pablo Pérez-Martínez, MD, PhD, are members of the Spanish Society of Arteriosclerosis and of the Spanish Society of Internal Medicine. They have coordinated an updated review of the leading scientific evidence surrounding artificial sweeteners: evidence showing that far from positively affecting our health, they have “negative effects for the cardiometabolic system.”
The paper, published in Current Opinion in Cardiology, delves into the consumption of these sweeteners and their negative influence on the development of obesity and of several of the most important cardiometabolic risk factors (hypertension, dyslipidemia, and diabetes).
Globalization and the increase in consumption of ultraprocessed foods have led to a need for greater knowledge on the health impacts of certain nutrients such as artificial sweeteners (nutritive and nonnutritive). This review aims to analyze their role and their effect on cardiometabolic and cardiovascular disease risk.
Cardiovascular risk
The detrimental effects of a high-calorie, high-sugar diet have been well established. For this reason, health authorities recommend limiting sugar consumption. The recommendation has led the food industry to develop different artificial sweeteners with specific properties, such as flavor and stability (nutritive artificial sweeteners), and others aimed at limiting sugar in the diet (nonnutritive artificial sweeteners). Recent evidence explores the influence of these two types of artificial sweeteners on cardiovascular disease risk through risk factors such as obesity and type 2 diabetes, among others.
Initially, the consumption of artificial sweeteners was presented as an alternative for reducing calorie intake in the diet as an option for people with excess weight and obesity. However, as this paper explains, the consumption of these artificial sweeteners favors weight gain because of neuroendocrine mechanisms related to satiety that are abnormally activated when artificial sweeteners are consumed.
Weight gain
On the other hand, evidence shows that consuming artificial sweeteners does not encourage weight loss. “Quite the contrary,” Dr. Pérez-Martínez, scientific director at the Maimonides Biomedical Research Institute and internist at the University Hospital Reina Sofia, both in Córdoba, told this news organization. “There is evidence showing weight gain resulting from the effect that artificial sweetener consumption has at the neurohormonal level by altering the mechanisms involved in regulating the feeling of satiety.”
However, on the basis of current evidence, sugar cannot be claimed to be less harmful. “What we do know is that in both cases, we should reduce or remove them from our diets and replace them with other healthier alternatives for weight management, such as eating plant-based products or being physically active.”
Confronting ignorance
Nonetheless, these recommendations are conditional, “because the weight of the evidence is not extremely high, since there have not been a whole lot of studies. All nutritional studies must be viewed with caution,” Manuel Anguita, MD, PhD, said in an interview. Dr. Anguita is department head of clinical cardiology at the University Hospital Reina Sofia in Córdoba and past president of the Spanish Society of Cardiology.
“It’s something that should be included within the medical record when you’re assessing cardiovascular risk. In addition to identifying patients who use artificial sweeteners, it’s especially important to emphasize that it’s not an appropriate recommendation for weight management.” Healthier measures include moderate exercise and the Mediterranean diet.
Explaining why this research is valuable, he said, “It’s generally useful because there’s ignorance not only in the population but among physicians as well [about] these negative effects of sweeteners.”
Diabetes and metabolic syndrome
Artificial sweeteners cause significant disruptions in the endocrine system, leading our metabolism to function abnormally. The review revealed that consuming artificial sweeteners raises the risk for type 2 diabetes by between 18% and 24% and raises the risk for metabolic syndrome by up to 44%.
Dr. Gómez-Delgado, an internal medicine specialist at the University Hospital of Jaen in Spain and first author of the study, discussed the deleterious effects of sweeteners on metabolism. “On one hand, neurohormonal disorders impact appetite, and the feeling of satiety is abnormally delayed.” On the other hand, “they induce excessive insulin secretion in the pancreas,” which in the long run, encourages metabolic disorders that lead to diabetes. Ultimately, this process produces what we know as “dysbiosis, since our microbiota is unable to process these artificial sweeteners.” Dysbiosis triggers specific pathophysiologic processes that negatively affect cardiometabolic and cardiovascular systems.
No differences
Regarding the type of sweetener, Dr. Gómez-Delgado noted that currently available studies assess the consumption of special dietary products that, in most cases, include various types of artificial sweeteners. “So, it’s not possible to define specific differences between them as to how they impact our health.” Additional studies are needed to confirm this effect at the cardiometabolic level and to analyze the different types of artificial sweeteners individually.
“There’s enough evidence to confirm that consuming artificial sweeteners negatively interferes with our metabolism – especially glucose metabolism – and increases the risk of developing diabetes,” said Dr. Gómez-Delgado.
High-sodium drinks
When it comes to the influence of artificial sweeteners on hypertension, “there is no single explanation. The World Health Organization already discussed this issue 4-5 years ago, not only due to their carcinogenic risk, but also due to this cardiovascular risk in terms of a lack of control of obesity, diabetes, and hypertension,” said Dr. Anguita.
Another important point “is that this is not in reference to the sweeteners themselves, but to soft drinks containing those components, which is where we have more studies,” he added. There are two factors explaining this increase in hypertension, which poses a problem at the population level, with medium- to long-term follow-up. “The sugary beverages that we mentioned have a higher sodium content. That is, the sweeteners add this element, which is a factor that’s directly linked to the increase in blood pressure levels.” Another factor that can influence blood pressure is “the increase in insulin secretion that has been described as resulting from sweeteners. In the medium and long term, this is associated with increased blood pressure levels.”
Cardiovascular risk factor?
Are artificial sweeteners considered to be a new cardiovascular risk factor? “What they really do is increase the incidence of the other classic risk factors,” including obesity, said Dr. Anguita. It has been shown that artificial sweeteners don’t reduce obesity when used continuously. Nonetheless, “there is still not enough evidence to view it in the same light as the classic risk factors,” added Dr. Anguita. However, it is a factor that can clearly worsen the control of the other factors. Therefore, “it’s appropriate to sound an alarm and explain that it’s not the best way to lose weight; there are many other healthier choices.”
“We need more robust evidence to take a clear position on the use of this type of sweetener and its detrimental effect on health. Meanwhile, it would be ideal to limit their consumption or even avoid adding artificial sweeteners to coffee or teas,” added Dr. Pérez-Martínez.
Regulate consumption
Dr. Pérez-Martínez mentioned that the measures proposed to regulate the consumption of artificial sweeteners and to modify the current legislation must involve “minimizing the consumption of these special dietary products as much as possible and even avoiding adding these artificial sweeteners to the foods that we consume; for example, to coffee and tea.” On the other hand, “we must provide consumers with information that is as clear and simple as possible regarding the composition of the food they consume and how it impacts their health.”
However, “we need more evidence to be able to take a clear position on what type of sweeteners we can consume in our diet and also to what extent we should limit their presence in the foods we consume,” said Dr. Pérez-Martínez.
Last, “most of the evidence is from short-term observational studies that assess frequencies and patterns of consumption of foods containing these artificial sweeteners.” Of course, “we need studies that specifically analyze their effects at the metabolic level as well as longer-term studies where the nutritional follow-up of participants is more accurate and rigorous, especially when it comes to the consumption of this type of food,” concluded Dr. Gómez-Delgado.
This article was translated from the Medscape Spanish Edition. A version appeared on Medscape.com.
It also shows evidence that these products are not beneficial for controlling excess weight.
Francisco Gómez-Delgado, MD, PhD, and Pablo Pérez-Martínez, MD, PhD, are members of the Spanish Society of Arteriosclerosis and of the Spanish Society of Internal Medicine. They have coordinated an updated review of the leading scientific evidence surrounding artificial sweeteners: evidence showing that far from positively affecting our health, they have “negative effects for the cardiometabolic system.”
The paper, published in Current Opinion in Cardiology, delves into the consumption of these sweeteners and their negative influence on the development of obesity and of several of the most important cardiometabolic risk factors (hypertension, dyslipidemia, and diabetes).
Globalization and the increase in consumption of ultraprocessed foods have led to a need for greater knowledge on the health impacts of certain nutrients such as artificial sweeteners (nutritive and nonnutritive). This review aims to analyze their role and their effect on cardiometabolic and cardiovascular disease risk.
Cardiovascular risk
The detrimental effects of a high-calorie, high-sugar diet have been well established. For this reason, health authorities recommend limiting sugar consumption. The recommendation has led the food industry to develop different artificial sweeteners with specific properties, such as flavor and stability (nutritive artificial sweeteners), and others aimed at limiting sugar in the diet (nonnutritive artificial sweeteners). Recent evidence explores the influence of these two types of artificial sweeteners on cardiovascular disease risk through risk factors such as obesity and type 2 diabetes, among others.
Initially, the consumption of artificial sweeteners was presented as an alternative for reducing calorie intake in the diet as an option for people with excess weight and obesity. However, as this paper explains, the consumption of these artificial sweeteners favors weight gain because of neuroendocrine mechanisms related to satiety that are abnormally activated when artificial sweeteners are consumed.
Weight gain
On the other hand, evidence shows that consuming artificial sweeteners does not encourage weight loss. “Quite the contrary,” Dr. Pérez-Martínez, scientific director at the Maimonides Biomedical Research Institute and internist at the University Hospital Reina Sofia, both in Córdoba, told this news organization. “There is evidence showing weight gain resulting from the effect that artificial sweetener consumption has at the neurohormonal level by altering the mechanisms involved in regulating the feeling of satiety.”
However, on the basis of current evidence, sugar cannot be claimed to be less harmful. “What we do know is that in both cases, we should reduce or remove them from our diets and replace them with other healthier alternatives for weight management, such as eating plant-based products or being physically active.”
Confronting ignorance
Nonetheless, these recommendations are conditional, “because the weight of the evidence is not extremely high, since there have not been a whole lot of studies. All nutritional studies must be viewed with caution,” Manuel Anguita, MD, PhD, said in an interview. Dr. Anguita is department head of clinical cardiology at the University Hospital Reina Sofia in Córdoba and past president of the Spanish Society of Cardiology.
“It’s something that should be included within the medical record when you’re assessing cardiovascular risk. In addition to identifying patients who use artificial sweeteners, it’s especially important to emphasize that it’s not an appropriate recommendation for weight management.” Healthier measures include moderate exercise and the Mediterranean diet.
Explaining why this research is valuable, he said, “It’s generally useful because there’s ignorance not only in the population but among physicians as well [about] these negative effects of sweeteners.”
Diabetes and metabolic syndrome
Artificial sweeteners cause significant disruptions in the endocrine system, leading our metabolism to function abnormally. The review revealed that consuming artificial sweeteners raises the risk for type 2 diabetes by between 18% and 24% and raises the risk for metabolic syndrome by up to 44%.
Dr. Gómez-Delgado, an internal medicine specialist at the University Hospital of Jaen in Spain and first author of the study, discussed the deleterious effects of sweeteners on metabolism. “On one hand, neurohormonal disorders impact appetite, and the feeling of satiety is abnormally delayed.” On the other hand, “they induce excessive insulin secretion in the pancreas,” which in the long run, encourages metabolic disorders that lead to diabetes. Ultimately, this process produces what we know as “dysbiosis, since our microbiota is unable to process these artificial sweeteners.” Dysbiosis triggers specific pathophysiologic processes that negatively affect cardiometabolic and cardiovascular systems.
No differences
Regarding the type of sweetener, Dr. Gómez-Delgado noted that currently available studies assess the consumption of special dietary products that, in most cases, include various types of artificial sweeteners. “So, it’s not possible to define specific differences between them as to how they impact our health.” Additional studies are needed to confirm this effect at the cardiometabolic level and to analyze the different types of artificial sweeteners individually.
“There’s enough evidence to confirm that consuming artificial sweeteners negatively interferes with our metabolism – especially glucose metabolism – and increases the risk of developing diabetes,” said Dr. Gómez-Delgado.
High-sodium drinks
When it comes to the influence of artificial sweeteners on hypertension, “there is no single explanation. The World Health Organization already discussed this issue 4-5 years ago, not only due to their carcinogenic risk, but also due to this cardiovascular risk in terms of a lack of control of obesity, diabetes, and hypertension,” said Dr. Anguita.
Another important point “is that this is not in reference to the sweeteners themselves, but to soft drinks containing those components, which is where we have more studies,” he added. There are two factors explaining this increase in hypertension, which poses a problem at the population level, with medium- to long-term follow-up. “The sugary beverages that we mentioned have a higher sodium content. That is, the sweeteners add this element, which is a factor that’s directly linked to the increase in blood pressure levels.” Another factor that can influence blood pressure is “the increase in insulin secretion that has been described as resulting from sweeteners. In the medium and long term, this is associated with increased blood pressure levels.”
Cardiovascular risk factor?
Are artificial sweeteners considered to be a new cardiovascular risk factor? “What they really do is increase the incidence of the other classic risk factors,” including obesity, said Dr. Anguita. It has been shown that artificial sweeteners don’t reduce obesity when used continuously. Nonetheless, “there is still not enough evidence to view it in the same light as the classic risk factors,” added Dr. Anguita. However, it is a factor that can clearly worsen the control of the other factors. Therefore, “it’s appropriate to sound an alarm and explain that it’s not the best way to lose weight; there are many other healthier choices.”
“We need more robust evidence to take a clear position on the use of this type of sweetener and its detrimental effect on health. Meanwhile, it would be ideal to limit their consumption or even avoid adding artificial sweeteners to coffee or teas,” added Dr. Pérez-Martínez.
Regulate consumption
Dr. Pérez-Martínez mentioned that the measures proposed to regulate the consumption of artificial sweeteners and to modify the current legislation must involve “minimizing the consumption of these special dietary products as much as possible and even avoiding adding these artificial sweeteners to the foods that we consume; for example, to coffee and tea.” On the other hand, “we must provide consumers with information that is as clear and simple as possible regarding the composition of the food they consume and how it impacts their health.”
However, “we need more evidence to be able to take a clear position on what type of sweeteners we can consume in our diet and also to what extent we should limit their presence in the foods we consume,” said Dr. Pérez-Martínez.
Last, “most of the evidence is from short-term observational studies that assess frequencies and patterns of consumption of foods containing these artificial sweeteners.” Of course, “we need studies that specifically analyze their effects at the metabolic level as well as longer-term studies where the nutritional follow-up of participants is more accurate and rigorous, especially when it comes to the consumption of this type of food,” concluded Dr. Gómez-Delgado.
This article was translated from the Medscape Spanish Edition. A version appeared on Medscape.com.
It also shows evidence that these products are not beneficial for controlling excess weight.
Francisco Gómez-Delgado, MD, PhD, and Pablo Pérez-Martínez, MD, PhD, are members of the Spanish Society of Arteriosclerosis and of the Spanish Society of Internal Medicine. They have coordinated an updated review of the leading scientific evidence surrounding artificial sweeteners: evidence showing that far from positively affecting our health, they have “negative effects for the cardiometabolic system.”
The paper, published in Current Opinion in Cardiology, delves into the consumption of these sweeteners and their negative influence on the development of obesity and of several of the most important cardiometabolic risk factors (hypertension, dyslipidemia, and diabetes).
Globalization and the increase in consumption of ultraprocessed foods have led to a need for greater knowledge on the health impacts of certain nutrients such as artificial sweeteners (nutritive and nonnutritive). This review aims to analyze their role and their effect on cardiometabolic and cardiovascular disease risk.
Cardiovascular risk
The detrimental effects of a high-calorie, high-sugar diet have been well established. For this reason, health authorities recommend limiting sugar consumption. The recommendation has led the food industry to develop different artificial sweeteners with specific properties, such as flavor and stability (nutritive artificial sweeteners), and others aimed at limiting sugar in the diet (nonnutritive artificial sweeteners). Recent evidence explores the influence of these two types of artificial sweeteners on cardiovascular disease risk through risk factors such as obesity and type 2 diabetes, among others.
Initially, the consumption of artificial sweeteners was presented as an alternative for reducing calorie intake in the diet as an option for people with excess weight and obesity. However, as this paper explains, the consumption of these artificial sweeteners favors weight gain because of neuroendocrine mechanisms related to satiety that are abnormally activated when artificial sweeteners are consumed.
Weight gain
On the other hand, evidence shows that consuming artificial sweeteners does not encourage weight loss. “Quite the contrary,” Dr. Pérez-Martínez, scientific director at the Maimonides Biomedical Research Institute and internist at the University Hospital Reina Sofia, both in Córdoba, told this news organization. “There is evidence showing weight gain resulting from the effect that artificial sweetener consumption has at the neurohormonal level by altering the mechanisms involved in regulating the feeling of satiety.”
However, on the basis of current evidence, sugar cannot be claimed to be less harmful. “What we do know is that in both cases, we should reduce or remove them from our diets and replace them with other healthier alternatives for weight management, such as eating plant-based products or being physically active.”
Confronting ignorance
Nonetheless, these recommendations are conditional, “because the weight of the evidence is not extremely high, since there have not been a whole lot of studies. All nutritional studies must be viewed with caution,” Manuel Anguita, MD, PhD, said in an interview. Dr. Anguita is department head of clinical cardiology at the University Hospital Reina Sofia in Córdoba and past president of the Spanish Society of Cardiology.
“It’s something that should be included within the medical record when you’re assessing cardiovascular risk. In addition to identifying patients who use artificial sweeteners, it’s especially important to emphasize that it’s not an appropriate recommendation for weight management.” Healthier measures include moderate exercise and the Mediterranean diet.
Explaining why this research is valuable, he said, “It’s generally useful because there’s ignorance not only in the population but among physicians as well [about] these negative effects of sweeteners.”
Diabetes and metabolic syndrome
Artificial sweeteners cause significant disruptions in the endocrine system, leading our metabolism to function abnormally. The review revealed that consuming artificial sweeteners raises the risk for type 2 diabetes by between 18% and 24% and raises the risk for metabolic syndrome by up to 44%.
Dr. Gómez-Delgado, an internal medicine specialist at the University Hospital of Jaen in Spain and first author of the study, discussed the deleterious effects of sweeteners on metabolism. “On one hand, neurohormonal disorders impact appetite, and the feeling of satiety is abnormally delayed.” On the other hand, “they induce excessive insulin secretion in the pancreas,” which in the long run, encourages metabolic disorders that lead to diabetes. Ultimately, this process produces what we know as “dysbiosis, since our microbiota is unable to process these artificial sweeteners.” Dysbiosis triggers specific pathophysiologic processes that negatively affect cardiometabolic and cardiovascular systems.
No differences
Regarding the type of sweetener, Dr. Gómez-Delgado noted that currently available studies assess the consumption of special dietary products that, in most cases, include various types of artificial sweeteners. “So, it’s not possible to define specific differences between them as to how they impact our health.” Additional studies are needed to confirm this effect at the cardiometabolic level and to analyze the different types of artificial sweeteners individually.
“There’s enough evidence to confirm that consuming artificial sweeteners negatively interferes with our metabolism – especially glucose metabolism – and increases the risk of developing diabetes,” said Dr. Gómez-Delgado.
High-sodium drinks
When it comes to the influence of artificial sweeteners on hypertension, “there is no single explanation. The World Health Organization already discussed this issue 4-5 years ago, not only due to their carcinogenic risk, but also due to this cardiovascular risk in terms of a lack of control of obesity, diabetes, and hypertension,” said Dr. Anguita.
Another important point “is that this is not in reference to the sweeteners themselves, but to soft drinks containing those components, which is where we have more studies,” he added. There are two factors explaining this increase in hypertension, which poses a problem at the population level, with medium- to long-term follow-up. “The sugary beverages that we mentioned have a higher sodium content. That is, the sweeteners add this element, which is a factor that’s directly linked to the increase in blood pressure levels.” Another factor that can influence blood pressure is “the increase in insulin secretion that has been described as resulting from sweeteners. In the medium and long term, this is associated with increased blood pressure levels.”
Cardiovascular risk factor?
Are artificial sweeteners considered to be a new cardiovascular risk factor? “What they really do is increase the incidence of the other classic risk factors,” including obesity, said Dr. Anguita. It has been shown that artificial sweeteners don’t reduce obesity when used continuously. Nonetheless, “there is still not enough evidence to view it in the same light as the classic risk factors,” added Dr. Anguita. However, it is a factor that can clearly worsen the control of the other factors. Therefore, “it’s appropriate to sound an alarm and explain that it’s not the best way to lose weight; there are many other healthier choices.”
“We need more robust evidence to take a clear position on the use of this type of sweetener and its detrimental effect on health. Meanwhile, it would be ideal to limit their consumption or even avoid adding artificial sweeteners to coffee or teas,” added Dr. Pérez-Martínez.
Regulate consumption
Dr. Pérez-Martínez mentioned that the measures proposed to regulate the consumption of artificial sweeteners and to modify the current legislation must involve “minimizing the consumption of these special dietary products as much as possible and even avoiding adding these artificial sweeteners to the foods that we consume; for example, to coffee and tea.” On the other hand, “we must provide consumers with information that is as clear and simple as possible regarding the composition of the food they consume and how it impacts their health.”
However, “we need more evidence to be able to take a clear position on what type of sweeteners we can consume in our diet and also to what extent we should limit their presence in the foods we consume,” said Dr. Pérez-Martínez.
Last, “most of the evidence is from short-term observational studies that assess frequencies and patterns of consumption of foods containing these artificial sweeteners.” Of course, “we need studies that specifically analyze their effects at the metabolic level as well as longer-term studies where the nutritional follow-up of participants is more accurate and rigorous, especially when it comes to the consumption of this type of food,” concluded Dr. Gómez-Delgado.
This article was translated from the Medscape Spanish Edition. A version appeared on Medscape.com.
FROM CURRENT OPINION IN CARDIOLOGY
Certain genes predict abdominal fat regain after weight loss
People with a genetic predisposition for abdominal adiposity regained more weight around their waist after weight loss than other people.
However, people with a genetic predisposition for a higher body mass index did not regain more weight after weight loss than others.
These findings are from a secondary analysis of data from participants in the Look AHEAD trial who had type 2 diabetes and overweight/obesity and had lost at least 3% of their initial weight after 1 year of intensive lifestyle intervention or control, who were followed for another 3 years.
The study showed that change in waist circumference (aka abdominal obesity) is regulated by a separate pathway from overall obesity during weight regain, the researchers report in their paper, published in Diabetes.
“These findings are the first of their kind and provide new insights into the mechanisms of weight regain,” they conclude.
“It was already known in the scientific literature that genes that are associated with abdominal fat deposition are different from the ones associated with overall obesity,” Malene Revsbech Christiansen, a PhD student, and Tuomas O. Kilpeläinen, PhD, associate professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, said in a joint email to this news organization.
Genetic variants associated with obesity are expressed in the central nervous system. However, genetic variants associated with waist circumference are expressed in the adipose tissues and might be involved in insulin sensitivity, or fat cell shape and differentiation, influencing how much adipose cells can expand in size or in number.
If those genes can function as targets for therapeutic agents, this might benefit patients who possess the genetic variants that predispose them to a higher waist-to-hip ratio adjusted for BMI (WHR-adjBMI), they said.
“However, this is a preliminary study that discovered an association between genetic variants and abdominal fat changes during weight loss,” they cautioned.
Further study is needed, they said, to test the associations in people without obesity and type 2 diabetes and to investigate this research question in people who underwent bariatric surgery or took weight-loss medications, “especially now that Wegovy has increased in popularity.”
“Genetic profiling,” they noted, “is becoming more popular as the prices go down, and future treatments are moving towards precision medicine, where treatments are tailored towards individuals rather than ‘one size fits all.’ ”
In the future, genetic tests might identify people who are more predisposed to abdominal fat deposition, hence needing more follow-up and help with lifestyle changes.
“For now, it does not seem realistic to test individuals for all these 481 [genetic] variants [predisposing to abdominal adiposity]. Each of these genetic variants predisposes, but is not deterministic, for the outcome, because of their individual small effects on waist circumference.”
“It should be stated,” they added, “that changing the diet, physical activity pattern, and behavior are still the main factors when losing weight and maintaining a healthy body.”
Maintaining weight loss is the big challenge
“Lifestyle interventions typically result in an average weight loss of 7%-10 % within 6 months; however, maintaining the weight loss is a significant challenge, as participants often regain an average one-third of the lost weight within 1 year and 50%-100% within 5 years,” the researchers write.
They aimed to study whether genetic predisposition to general or abdominal obesity predicts weight gain after weight loss, based on data from 822 women and 593 men in the Look AHEAD trial.
On average, at 1 year after the intervention, the participants in the intensive lifestyle group lost 24 lbs (10.9 kg) and 3.55 inches (9 cm) around the waist, and participants in the control group lost 15 lbs (6.8 kg) pounds and 1.98 inches (5 cm) around the waist.
From year 1 to year 2, participants in the intensive lifestyle group regained 6.09 lbs and 0.98 inches around the waist, and participants in the control group lost 1.41 lbs and 0.17 inches around the waist.
From year 1 to year 4, participants in the intensive lifestyle group regained 11.05 lbs and 1.92 inches around the waist, and participants in the control group lost 2.24 lbs and 0.76 inches around the waist.
From genome-wide association studies (GWAS) in about 700,000 mainly White individuals of European origin, the researchers constructed a genetic risk score based on 894 independent single nucleotide polymorphisms (SNPs) associated with high BMI and another genetic risk score based on 481 SNPs associated with high WHR-adjBMI.
Having a genetic predisposition to higher WHR-adjBMI predicted an increase in abdominal obesity after weight loss, whereas having a genetic predisposition to higher BMI did not predict weight regain.
“These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain,” the researchers conclude.
The researchers were supported by grants from the Novo Nordisk Foundation and the Danish Diabetes Academy (funded by the Novo Nordisk Foundation). The authors report no relevant financial relationships.
A version of this article appeared on Medscape.com.
People with a genetic predisposition for abdominal adiposity regained more weight around their waist after weight loss than other people.
However, people with a genetic predisposition for a higher body mass index did not regain more weight after weight loss than others.
These findings are from a secondary analysis of data from participants in the Look AHEAD trial who had type 2 diabetes and overweight/obesity and had lost at least 3% of their initial weight after 1 year of intensive lifestyle intervention or control, who were followed for another 3 years.
The study showed that change in waist circumference (aka abdominal obesity) is regulated by a separate pathway from overall obesity during weight regain, the researchers report in their paper, published in Diabetes.
“These findings are the first of their kind and provide new insights into the mechanisms of weight regain,” they conclude.
“It was already known in the scientific literature that genes that are associated with abdominal fat deposition are different from the ones associated with overall obesity,” Malene Revsbech Christiansen, a PhD student, and Tuomas O. Kilpeläinen, PhD, associate professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, said in a joint email to this news organization.
Genetic variants associated with obesity are expressed in the central nervous system. However, genetic variants associated with waist circumference are expressed in the adipose tissues and might be involved in insulin sensitivity, or fat cell shape and differentiation, influencing how much adipose cells can expand in size or in number.
If those genes can function as targets for therapeutic agents, this might benefit patients who possess the genetic variants that predispose them to a higher waist-to-hip ratio adjusted for BMI (WHR-adjBMI), they said.
“However, this is a preliminary study that discovered an association between genetic variants and abdominal fat changes during weight loss,” they cautioned.
Further study is needed, they said, to test the associations in people without obesity and type 2 diabetes and to investigate this research question in people who underwent bariatric surgery or took weight-loss medications, “especially now that Wegovy has increased in popularity.”
“Genetic profiling,” they noted, “is becoming more popular as the prices go down, and future treatments are moving towards precision medicine, where treatments are tailored towards individuals rather than ‘one size fits all.’ ”
In the future, genetic tests might identify people who are more predisposed to abdominal fat deposition, hence needing more follow-up and help with lifestyle changes.
“For now, it does not seem realistic to test individuals for all these 481 [genetic] variants [predisposing to abdominal adiposity]. Each of these genetic variants predisposes, but is not deterministic, for the outcome, because of their individual small effects on waist circumference.”
“It should be stated,” they added, “that changing the diet, physical activity pattern, and behavior are still the main factors when losing weight and maintaining a healthy body.”
Maintaining weight loss is the big challenge
“Lifestyle interventions typically result in an average weight loss of 7%-10 % within 6 months; however, maintaining the weight loss is a significant challenge, as participants often regain an average one-third of the lost weight within 1 year and 50%-100% within 5 years,” the researchers write.
They aimed to study whether genetic predisposition to general or abdominal obesity predicts weight gain after weight loss, based on data from 822 women and 593 men in the Look AHEAD trial.
On average, at 1 year after the intervention, the participants in the intensive lifestyle group lost 24 lbs (10.9 kg) and 3.55 inches (9 cm) around the waist, and participants in the control group lost 15 lbs (6.8 kg) pounds and 1.98 inches (5 cm) around the waist.
From year 1 to year 2, participants in the intensive lifestyle group regained 6.09 lbs and 0.98 inches around the waist, and participants in the control group lost 1.41 lbs and 0.17 inches around the waist.
From year 1 to year 4, participants in the intensive lifestyle group regained 11.05 lbs and 1.92 inches around the waist, and participants in the control group lost 2.24 lbs and 0.76 inches around the waist.
From genome-wide association studies (GWAS) in about 700,000 mainly White individuals of European origin, the researchers constructed a genetic risk score based on 894 independent single nucleotide polymorphisms (SNPs) associated with high BMI and another genetic risk score based on 481 SNPs associated with high WHR-adjBMI.
Having a genetic predisposition to higher WHR-adjBMI predicted an increase in abdominal obesity after weight loss, whereas having a genetic predisposition to higher BMI did not predict weight regain.
“These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain,” the researchers conclude.
The researchers were supported by grants from the Novo Nordisk Foundation and the Danish Diabetes Academy (funded by the Novo Nordisk Foundation). The authors report no relevant financial relationships.
A version of this article appeared on Medscape.com.
People with a genetic predisposition for abdominal adiposity regained more weight around their waist after weight loss than other people.
However, people with a genetic predisposition for a higher body mass index did not regain more weight after weight loss than others.
These findings are from a secondary analysis of data from participants in the Look AHEAD trial who had type 2 diabetes and overweight/obesity and had lost at least 3% of their initial weight after 1 year of intensive lifestyle intervention or control, who were followed for another 3 years.
The study showed that change in waist circumference (aka abdominal obesity) is regulated by a separate pathway from overall obesity during weight regain, the researchers report in their paper, published in Diabetes.
“These findings are the first of their kind and provide new insights into the mechanisms of weight regain,” they conclude.
“It was already known in the scientific literature that genes that are associated with abdominal fat deposition are different from the ones associated with overall obesity,” Malene Revsbech Christiansen, a PhD student, and Tuomas O. Kilpeläinen, PhD, associate professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, said in a joint email to this news organization.
Genetic variants associated with obesity are expressed in the central nervous system. However, genetic variants associated with waist circumference are expressed in the adipose tissues and might be involved in insulin sensitivity, or fat cell shape and differentiation, influencing how much adipose cells can expand in size or in number.
If those genes can function as targets for therapeutic agents, this might benefit patients who possess the genetic variants that predispose them to a higher waist-to-hip ratio adjusted for BMI (WHR-adjBMI), they said.
“However, this is a preliminary study that discovered an association between genetic variants and abdominal fat changes during weight loss,” they cautioned.
Further study is needed, they said, to test the associations in people without obesity and type 2 diabetes and to investigate this research question in people who underwent bariatric surgery or took weight-loss medications, “especially now that Wegovy has increased in popularity.”
“Genetic profiling,” they noted, “is becoming more popular as the prices go down, and future treatments are moving towards precision medicine, where treatments are tailored towards individuals rather than ‘one size fits all.’ ”
In the future, genetic tests might identify people who are more predisposed to abdominal fat deposition, hence needing more follow-up and help with lifestyle changes.
“For now, it does not seem realistic to test individuals for all these 481 [genetic] variants [predisposing to abdominal adiposity]. Each of these genetic variants predisposes, but is not deterministic, for the outcome, because of their individual small effects on waist circumference.”
“It should be stated,” they added, “that changing the diet, physical activity pattern, and behavior are still the main factors when losing weight and maintaining a healthy body.”
Maintaining weight loss is the big challenge
“Lifestyle interventions typically result in an average weight loss of 7%-10 % within 6 months; however, maintaining the weight loss is a significant challenge, as participants often regain an average one-third of the lost weight within 1 year and 50%-100% within 5 years,” the researchers write.
They aimed to study whether genetic predisposition to general or abdominal obesity predicts weight gain after weight loss, based on data from 822 women and 593 men in the Look AHEAD trial.
On average, at 1 year after the intervention, the participants in the intensive lifestyle group lost 24 lbs (10.9 kg) and 3.55 inches (9 cm) around the waist, and participants in the control group lost 15 lbs (6.8 kg) pounds and 1.98 inches (5 cm) around the waist.
From year 1 to year 2, participants in the intensive lifestyle group regained 6.09 lbs and 0.98 inches around the waist, and participants in the control group lost 1.41 lbs and 0.17 inches around the waist.
From year 1 to year 4, participants in the intensive lifestyle group regained 11.05 lbs and 1.92 inches around the waist, and participants in the control group lost 2.24 lbs and 0.76 inches around the waist.
From genome-wide association studies (GWAS) in about 700,000 mainly White individuals of European origin, the researchers constructed a genetic risk score based on 894 independent single nucleotide polymorphisms (SNPs) associated with high BMI and another genetic risk score based on 481 SNPs associated with high WHR-adjBMI.
Having a genetic predisposition to higher WHR-adjBMI predicted an increase in abdominal obesity after weight loss, whereas having a genetic predisposition to higher BMI did not predict weight regain.
“These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain,” the researchers conclude.
The researchers were supported by grants from the Novo Nordisk Foundation and the Danish Diabetes Academy (funded by the Novo Nordisk Foundation). The authors report no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM DIABETES
Obesity Guidelines
‘Water fasting’ benefits don’t last
Health benefits of prolonged “water fasting” (zero calories) or Buchinger fasting (200-300 calories/day) don’t last, according to authors of a review of eight studies.
Five days of fasting lowered weight by about 6%, but this weight was regained after 3 months of regular eating, the investigators found. The article was published in Nutrition Reviews.
“Water fasting led to improvements in blood pressure, cholesterol, and blood sugar levels, but these were short-lived,” senior author Krista A. Varady, PhD, told this news organization.
“Levels returned to baseline ... quickly after participants started eating. Most benefits disappeared in 3-4 months,” said Dr. Varady, professor of nutrition at the University of Illinois, Chicago.
“My overall conclusion,” she said, “is that I guess you could try it, but it just seems like a lot of work, and all those metabolic benefits disappear. I would encourage someone hoping to lose weight to try intermittent fasting instead of water fasting, because there’s a lot more data to show it can help with weight management.
“People should consult their doctor if they have diabetes or any other major obesity-related conditions before doing water fasting,” Dr. Varady cautioned.
“Healthy people with obesity can probably fast safely for 5 days on their own (if they don’t have any other conditions). However, no one should undertake one of these fasts for more than 5 days without medical supervision,” she stressed.
Eight studies of water and Buchinger fasting
Although several favorable effects of prolonged fasting have been observed, benefits must be weighed against risks, Dr. Varady and her coauthors wrote.
Most medically supervised fasting programs have reported only minor adverse events, which included hunger, headaches, nausea, vomiting, dry mouth, and fatigue. However, more severe events have been documented, including edema, abnormal results on liver function tests, decreased bone density, and metabolic acidosis.
The researchers aimed to determine the effect of prolonged fasting on weight, blood pressure, lipid levels, and glycemic control, as well as safety and the effects of refeeding.
They examined two types of prolonged fasting: water fasting and Buchinger fasting, which involves consuming 250 mL of fruit or vegetable juice for lunch and 250 mL of soup for dinner every day of the 5- to 20-day fast.
Buchinger fasting is popular in Central Europe. Water fasting “institutes” exist in the United States, such as one in California, Dr. Varady noted.
The researchers excluded fasting during Ramadan or fasting practiced by Seventh Day Adventists.
They identified four studies of water fasting and four studies of Buchinger fasting (of which one study of 1,422 participants assessed fasting for 5, 10, 15, and 20 days).
The review showed that prolonged fasting for 5-20 days produced large increases in circulating ketones, weight loss of 2%-10%, and decreases in systolic and diastolic blood pressure.
People who fasted 5 days typically lost 4%-6% of their weight; those who fasted 7-10 days lost 2%-10% of their weight; and those who fasted 15-20 days lost 7%-10% of their weight.
LDL cholesterol and triglyceride levels decreased in some trials.
Fasting glucose levels, fasting insulin levels, insulin resistance, and A1c decreased in adults without diabetes but remained unchanged in patients with type 1 or type 2 diabetes.
Some participants experienced metabolic acidosis, headaches, insomnia, or hunger.
About two-thirds of the weight lost was of lean mass, and one-third was of fat mass. The loss of lean mass loss suggests that prolonged fasting may increase the breakdown of muscle proteins, which is a concern, the researchers noted.
Few of the trials examined the effects of refeeding. In one study, normal-weight adults lost 6% of their weight after 5 days of water-only fasting but then gained it all back after 3 months of eating regularly.
In three trials, participants regained 1%-2% of their weight 2-4 months after fasting; however, those trials instructed participants to follow a calorie-restricted diet during the refeeding period.
Three to 4 months after the fast was completed, none of the metabolic benefits were maintained, even when weight loss was maintained.
The study did not receive external funding. Dr. Varady has received author fees from Hachette Book Group for “The Every Other Day Diet” and from Pan Macmillan Press for “The Fastest Diet.” The other authors have disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Health benefits of prolonged “water fasting” (zero calories) or Buchinger fasting (200-300 calories/day) don’t last, according to authors of a review of eight studies.
Five days of fasting lowered weight by about 6%, but this weight was regained after 3 months of regular eating, the investigators found. The article was published in Nutrition Reviews.
“Water fasting led to improvements in blood pressure, cholesterol, and blood sugar levels, but these were short-lived,” senior author Krista A. Varady, PhD, told this news organization.
“Levels returned to baseline ... quickly after participants started eating. Most benefits disappeared in 3-4 months,” said Dr. Varady, professor of nutrition at the University of Illinois, Chicago.
“My overall conclusion,” she said, “is that I guess you could try it, but it just seems like a lot of work, and all those metabolic benefits disappear. I would encourage someone hoping to lose weight to try intermittent fasting instead of water fasting, because there’s a lot more data to show it can help with weight management.
“People should consult their doctor if they have diabetes or any other major obesity-related conditions before doing water fasting,” Dr. Varady cautioned.
“Healthy people with obesity can probably fast safely for 5 days on their own (if they don’t have any other conditions). However, no one should undertake one of these fasts for more than 5 days without medical supervision,” she stressed.
Eight studies of water and Buchinger fasting
Although several favorable effects of prolonged fasting have been observed, benefits must be weighed against risks, Dr. Varady and her coauthors wrote.
Most medically supervised fasting programs have reported only minor adverse events, which included hunger, headaches, nausea, vomiting, dry mouth, and fatigue. However, more severe events have been documented, including edema, abnormal results on liver function tests, decreased bone density, and metabolic acidosis.
The researchers aimed to determine the effect of prolonged fasting on weight, blood pressure, lipid levels, and glycemic control, as well as safety and the effects of refeeding.
They examined two types of prolonged fasting: water fasting and Buchinger fasting, which involves consuming 250 mL of fruit or vegetable juice for lunch and 250 mL of soup for dinner every day of the 5- to 20-day fast.
Buchinger fasting is popular in Central Europe. Water fasting “institutes” exist in the United States, such as one in California, Dr. Varady noted.
The researchers excluded fasting during Ramadan or fasting practiced by Seventh Day Adventists.
They identified four studies of water fasting and four studies of Buchinger fasting (of which one study of 1,422 participants assessed fasting for 5, 10, 15, and 20 days).
The review showed that prolonged fasting for 5-20 days produced large increases in circulating ketones, weight loss of 2%-10%, and decreases in systolic and diastolic blood pressure.
People who fasted 5 days typically lost 4%-6% of their weight; those who fasted 7-10 days lost 2%-10% of their weight; and those who fasted 15-20 days lost 7%-10% of their weight.
LDL cholesterol and triglyceride levels decreased in some trials.
Fasting glucose levels, fasting insulin levels, insulin resistance, and A1c decreased in adults without diabetes but remained unchanged in patients with type 1 or type 2 diabetes.
Some participants experienced metabolic acidosis, headaches, insomnia, or hunger.
About two-thirds of the weight lost was of lean mass, and one-third was of fat mass. The loss of lean mass loss suggests that prolonged fasting may increase the breakdown of muscle proteins, which is a concern, the researchers noted.
Few of the trials examined the effects of refeeding. In one study, normal-weight adults lost 6% of their weight after 5 days of water-only fasting but then gained it all back after 3 months of eating regularly.
In three trials, participants regained 1%-2% of their weight 2-4 months after fasting; however, those trials instructed participants to follow a calorie-restricted diet during the refeeding period.
Three to 4 months after the fast was completed, none of the metabolic benefits were maintained, even when weight loss was maintained.
The study did not receive external funding. Dr. Varady has received author fees from Hachette Book Group for “The Every Other Day Diet” and from Pan Macmillan Press for “The Fastest Diet.” The other authors have disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Health benefits of prolonged “water fasting” (zero calories) or Buchinger fasting (200-300 calories/day) don’t last, according to authors of a review of eight studies.
Five days of fasting lowered weight by about 6%, but this weight was regained after 3 months of regular eating, the investigators found. The article was published in Nutrition Reviews.
“Water fasting led to improvements in blood pressure, cholesterol, and blood sugar levels, but these were short-lived,” senior author Krista A. Varady, PhD, told this news organization.
“Levels returned to baseline ... quickly after participants started eating. Most benefits disappeared in 3-4 months,” said Dr. Varady, professor of nutrition at the University of Illinois, Chicago.
“My overall conclusion,” she said, “is that I guess you could try it, but it just seems like a lot of work, and all those metabolic benefits disappear. I would encourage someone hoping to lose weight to try intermittent fasting instead of water fasting, because there’s a lot more data to show it can help with weight management.
“People should consult their doctor if they have diabetes or any other major obesity-related conditions before doing water fasting,” Dr. Varady cautioned.
“Healthy people with obesity can probably fast safely for 5 days on their own (if they don’t have any other conditions). However, no one should undertake one of these fasts for more than 5 days without medical supervision,” she stressed.
Eight studies of water and Buchinger fasting
Although several favorable effects of prolonged fasting have been observed, benefits must be weighed against risks, Dr. Varady and her coauthors wrote.
Most medically supervised fasting programs have reported only minor adverse events, which included hunger, headaches, nausea, vomiting, dry mouth, and fatigue. However, more severe events have been documented, including edema, abnormal results on liver function tests, decreased bone density, and metabolic acidosis.
The researchers aimed to determine the effect of prolonged fasting on weight, blood pressure, lipid levels, and glycemic control, as well as safety and the effects of refeeding.
They examined two types of prolonged fasting: water fasting and Buchinger fasting, which involves consuming 250 mL of fruit or vegetable juice for lunch and 250 mL of soup for dinner every day of the 5- to 20-day fast.
Buchinger fasting is popular in Central Europe. Water fasting “institutes” exist in the United States, such as one in California, Dr. Varady noted.
The researchers excluded fasting during Ramadan or fasting practiced by Seventh Day Adventists.
They identified four studies of water fasting and four studies of Buchinger fasting (of which one study of 1,422 participants assessed fasting for 5, 10, 15, and 20 days).
The review showed that prolonged fasting for 5-20 days produced large increases in circulating ketones, weight loss of 2%-10%, and decreases in systolic and diastolic blood pressure.
People who fasted 5 days typically lost 4%-6% of their weight; those who fasted 7-10 days lost 2%-10% of their weight; and those who fasted 15-20 days lost 7%-10% of their weight.
LDL cholesterol and triglyceride levels decreased in some trials.
Fasting glucose levels, fasting insulin levels, insulin resistance, and A1c decreased in adults without diabetes but remained unchanged in patients with type 1 or type 2 diabetes.
Some participants experienced metabolic acidosis, headaches, insomnia, or hunger.
About two-thirds of the weight lost was of lean mass, and one-third was of fat mass. The loss of lean mass loss suggests that prolonged fasting may increase the breakdown of muscle proteins, which is a concern, the researchers noted.
Few of the trials examined the effects of refeeding. In one study, normal-weight adults lost 6% of their weight after 5 days of water-only fasting but then gained it all back after 3 months of eating regularly.
In three trials, participants regained 1%-2% of their weight 2-4 months after fasting; however, those trials instructed participants to follow a calorie-restricted diet during the refeeding period.
Three to 4 months after the fast was completed, none of the metabolic benefits were maintained, even when weight loss was maintained.
The study did not receive external funding. Dr. Varady has received author fees from Hachette Book Group for “The Every Other Day Diet” and from Pan Macmillan Press for “The Fastest Diet.” The other authors have disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
New weight loss drugs appeal to half of U.S. adults
A recent survey of more than 1,000 U.S. adults showed that 18% were “somewhat interested” in taking a “safe, effective” weight loss drug, 27% were “very interested,” and 4% said they were already using such an agent, together constituting 49% of the surveyed adults.
The newer, more potent and generally safe agents that work by stimulating receptors to nutrient-stimulated hormones, such as incretins like glucagonlike peptide–1, seem to drive this interest.
When asked: “How much have you heard, if anything, about a new class of drugs being used for weight loss, such as Ozempic [semaglutide formulated and approved for people with type 2 diabetes], Wegovy [semaglutide for weight loss], and Mounjaro [tirzepatide, currently approved for treating only people with type 2 diabetes]?” 43% said they had heard some, or a lot, about these agents.
This was particularly true among people at least 65 years old, who had a 55% prevalence of knowing some, or a lot, about these new weight-loss agents, while an additional 26% had heard at least “a little” about them, reported staff members of KFF (formerly the Kaiser Family Foundation) in a report posted online in early August.
Weight loss drugs garner ‘increasing’ attention
“A new class of prescription drugs, initially developed to treat type 2 diabetes, have been garnering an increasing amount of attention due to their ability to act as highly effective weight loss drugs for overweight or obese adults,” wrote the report’s authors.
However, surveyed interest fell markedly when respondents answered further questions that hinged on certain limitations of the newer weight loss formulations.
For example, the percent interested held nearly steady, at 44%, when told the weight loss agent in question was an oral pill, but when asked about formulations requiring weekly injections the prevalence of people who had some interest, or were very interested, dropped to 23%. And when presented with the premise that they would need to take the drug chronically to keep their weight off and that stopping the agent would mean weight regain, those with “higher levels of interest” in the agent fell to 14% of the study sample.
Other deal breakers for most survey respondents were lack of a weight-loss indication approved by the Food and Drug Administration, a hypothetical that left 16% still somewhat or very interested, and lack of insurance coverage, which also dropped the higher interest levels to 16% of respondents. On the flip side of that sentiment, 80% of survey respondents believe that health insurance should cover the cost for a prescription weight loss drug for people with overweight or obesity.
The survey was designed and analyzed by public-opinion researchers at KFF and run both online and by telephone in both English and Spanish during July 11-19, 2023. The margin of sampling error was plus or minus 3 percentage points for the full sample but may have been even higher for results based on subgroup analyses.
The survey report includes no funding or disclosure information. However, KFF describes itself as “independent” and “nonpartisan” and that it “does everything based on facts and data, and we do so objectively without taking policy positions and without affiliation to any political party or external interest.”
A version of this article first appeared on Medscape.com.
A recent survey of more than 1,000 U.S. adults showed that 18% were “somewhat interested” in taking a “safe, effective” weight loss drug, 27% were “very interested,” and 4% said they were already using such an agent, together constituting 49% of the surveyed adults.
The newer, more potent and generally safe agents that work by stimulating receptors to nutrient-stimulated hormones, such as incretins like glucagonlike peptide–1, seem to drive this interest.
When asked: “How much have you heard, if anything, about a new class of drugs being used for weight loss, such as Ozempic [semaglutide formulated and approved for people with type 2 diabetes], Wegovy [semaglutide for weight loss], and Mounjaro [tirzepatide, currently approved for treating only people with type 2 diabetes]?” 43% said they had heard some, or a lot, about these agents.
This was particularly true among people at least 65 years old, who had a 55% prevalence of knowing some, or a lot, about these new weight-loss agents, while an additional 26% had heard at least “a little” about them, reported staff members of KFF (formerly the Kaiser Family Foundation) in a report posted online in early August.
Weight loss drugs garner ‘increasing’ attention
“A new class of prescription drugs, initially developed to treat type 2 diabetes, have been garnering an increasing amount of attention due to their ability to act as highly effective weight loss drugs for overweight or obese adults,” wrote the report’s authors.
However, surveyed interest fell markedly when respondents answered further questions that hinged on certain limitations of the newer weight loss formulations.
For example, the percent interested held nearly steady, at 44%, when told the weight loss agent in question was an oral pill, but when asked about formulations requiring weekly injections the prevalence of people who had some interest, or were very interested, dropped to 23%. And when presented with the premise that they would need to take the drug chronically to keep their weight off and that stopping the agent would mean weight regain, those with “higher levels of interest” in the agent fell to 14% of the study sample.
Other deal breakers for most survey respondents were lack of a weight-loss indication approved by the Food and Drug Administration, a hypothetical that left 16% still somewhat or very interested, and lack of insurance coverage, which also dropped the higher interest levels to 16% of respondents. On the flip side of that sentiment, 80% of survey respondents believe that health insurance should cover the cost for a prescription weight loss drug for people with overweight or obesity.
The survey was designed and analyzed by public-opinion researchers at KFF and run both online and by telephone in both English and Spanish during July 11-19, 2023. The margin of sampling error was plus or minus 3 percentage points for the full sample but may have been even higher for results based on subgroup analyses.
The survey report includes no funding or disclosure information. However, KFF describes itself as “independent” and “nonpartisan” and that it “does everything based on facts and data, and we do so objectively without taking policy positions and without affiliation to any political party or external interest.”
A version of this article first appeared on Medscape.com.
A recent survey of more than 1,000 U.S. adults showed that 18% were “somewhat interested” in taking a “safe, effective” weight loss drug, 27% were “very interested,” and 4% said they were already using such an agent, together constituting 49% of the surveyed adults.
The newer, more potent and generally safe agents that work by stimulating receptors to nutrient-stimulated hormones, such as incretins like glucagonlike peptide–1, seem to drive this interest.
When asked: “How much have you heard, if anything, about a new class of drugs being used for weight loss, such as Ozempic [semaglutide formulated and approved for people with type 2 diabetes], Wegovy [semaglutide for weight loss], and Mounjaro [tirzepatide, currently approved for treating only people with type 2 diabetes]?” 43% said they had heard some, or a lot, about these agents.
This was particularly true among people at least 65 years old, who had a 55% prevalence of knowing some, or a lot, about these new weight-loss agents, while an additional 26% had heard at least “a little” about them, reported staff members of KFF (formerly the Kaiser Family Foundation) in a report posted online in early August.
Weight loss drugs garner ‘increasing’ attention
“A new class of prescription drugs, initially developed to treat type 2 diabetes, have been garnering an increasing amount of attention due to their ability to act as highly effective weight loss drugs for overweight or obese adults,” wrote the report’s authors.
However, surveyed interest fell markedly when respondents answered further questions that hinged on certain limitations of the newer weight loss formulations.
For example, the percent interested held nearly steady, at 44%, when told the weight loss agent in question was an oral pill, but when asked about formulations requiring weekly injections the prevalence of people who had some interest, or were very interested, dropped to 23%. And when presented with the premise that they would need to take the drug chronically to keep their weight off and that stopping the agent would mean weight regain, those with “higher levels of interest” in the agent fell to 14% of the study sample.
Other deal breakers for most survey respondents were lack of a weight-loss indication approved by the Food and Drug Administration, a hypothetical that left 16% still somewhat or very interested, and lack of insurance coverage, which also dropped the higher interest levels to 16% of respondents. On the flip side of that sentiment, 80% of survey respondents believe that health insurance should cover the cost for a prescription weight loss drug for people with overweight or obesity.
The survey was designed and analyzed by public-opinion researchers at KFF and run both online and by telephone in both English and Spanish during July 11-19, 2023. The margin of sampling error was plus or minus 3 percentage points for the full sample but may have been even higher for results based on subgroup analyses.
The survey report includes no funding or disclosure information. However, KFF describes itself as “independent” and “nonpartisan” and that it “does everything based on facts and data, and we do so objectively without taking policy positions and without affiliation to any political party or external interest.”
A version of this article first appeared on Medscape.com.
Study documents obesity-related defecation disorders
, as well as clinically significant rectocele and increased anal resting and rectal pressures.
The study, which was published in the American Journal of Gastroenterology and led by Pam Chaichanavichkij, MBChB, MRCS, of Queen Mary University, London, included 1,155 patients (84% female, median age 52) who were obese (31.7%), overweight (34.8%), or of normal weight 33.5%).
“These results support the notion that rectal evacuation disorder/incomplete evacuation may be an important underlying mechanism for fecal incontinence in obese patients,” the authors wrote.
Obese patients had higher odds of fecal incontinence to liquid stools (69.9 vs. 47.8%; odds ratio, 1.96 [confidence interval, 1.43-2.70]), use of containment products (54.6% vs. 32.6%; OR, 1.81 [CI, 1.31-2.51]), fecal urgency (74.6% vs. 60.7%; OR, 1.54 [CI, 1.11-2.14]), urge fecal incontinence (63.4% vs. 47.3%, OR, 1.68 [CI, 1.23-2.29]), and vaginal digitation (18.0% vs. 9.7%; OR, 2.18 [CI, 1.26-3.86]).
Obese patients were also more likely to have functional constipation (50.3%), compared with overweight (44.8%) and normal weight patients (41.1%).
There was a positive linear association between body mass index (BMI) and anal resting pressure (beta 0.45; R2, 0.25, P = 0.0003), though the odds of anal hypertension were not significantly higher after Benjamini-Hochberg correction. Obese patients more often had a large clinically significant rectocele (34.4% vs. 20.6%; OR, 2.62 [CI, 1.51-4.55]), compared with normal BMI patients.
The data showed higher rates of gynecological surgery, cholecystectomy, diabetes, and self-reported use of opioids, antidepressants, and anticholinergic medications in the obese group, compared with the others.
In morphological differences measured by x-ray defecography, obese patients had more than two-fold higher odds of having a rectocele and even greater odds of the rectocele being large and clinically significant. Anal and rectal resting pressures were linearly related to increasing BMI, the authors report.
Because most patients in the study were female, the findings may not be generalizable to the general population or male patients. Also, diet and exercise, two factors that may affect defecation disorders, were not accounted for in this study.
Dr. Chaichanavichkij reported no disclosures. Two other authors reported financial relationships with Medtronic Inc. and MMS/Laborie.
, as well as clinically significant rectocele and increased anal resting and rectal pressures.
The study, which was published in the American Journal of Gastroenterology and led by Pam Chaichanavichkij, MBChB, MRCS, of Queen Mary University, London, included 1,155 patients (84% female, median age 52) who were obese (31.7%), overweight (34.8%), or of normal weight 33.5%).
“These results support the notion that rectal evacuation disorder/incomplete evacuation may be an important underlying mechanism for fecal incontinence in obese patients,” the authors wrote.
Obese patients had higher odds of fecal incontinence to liquid stools (69.9 vs. 47.8%; odds ratio, 1.96 [confidence interval, 1.43-2.70]), use of containment products (54.6% vs. 32.6%; OR, 1.81 [CI, 1.31-2.51]), fecal urgency (74.6% vs. 60.7%; OR, 1.54 [CI, 1.11-2.14]), urge fecal incontinence (63.4% vs. 47.3%, OR, 1.68 [CI, 1.23-2.29]), and vaginal digitation (18.0% vs. 9.7%; OR, 2.18 [CI, 1.26-3.86]).
Obese patients were also more likely to have functional constipation (50.3%), compared with overweight (44.8%) and normal weight patients (41.1%).
There was a positive linear association between body mass index (BMI) and anal resting pressure (beta 0.45; R2, 0.25, P = 0.0003), though the odds of anal hypertension were not significantly higher after Benjamini-Hochberg correction. Obese patients more often had a large clinically significant rectocele (34.4% vs. 20.6%; OR, 2.62 [CI, 1.51-4.55]), compared with normal BMI patients.
The data showed higher rates of gynecological surgery, cholecystectomy, diabetes, and self-reported use of opioids, antidepressants, and anticholinergic medications in the obese group, compared with the others.
In morphological differences measured by x-ray defecography, obese patients had more than two-fold higher odds of having a rectocele and even greater odds of the rectocele being large and clinically significant. Anal and rectal resting pressures were linearly related to increasing BMI, the authors report.
Because most patients in the study were female, the findings may not be generalizable to the general population or male patients. Also, diet and exercise, two factors that may affect defecation disorders, were not accounted for in this study.
Dr. Chaichanavichkij reported no disclosures. Two other authors reported financial relationships with Medtronic Inc. and MMS/Laborie.
, as well as clinically significant rectocele and increased anal resting and rectal pressures.
The study, which was published in the American Journal of Gastroenterology and led by Pam Chaichanavichkij, MBChB, MRCS, of Queen Mary University, London, included 1,155 patients (84% female, median age 52) who were obese (31.7%), overweight (34.8%), or of normal weight 33.5%).
“These results support the notion that rectal evacuation disorder/incomplete evacuation may be an important underlying mechanism for fecal incontinence in obese patients,” the authors wrote.
Obese patients had higher odds of fecal incontinence to liquid stools (69.9 vs. 47.8%; odds ratio, 1.96 [confidence interval, 1.43-2.70]), use of containment products (54.6% vs. 32.6%; OR, 1.81 [CI, 1.31-2.51]), fecal urgency (74.6% vs. 60.7%; OR, 1.54 [CI, 1.11-2.14]), urge fecal incontinence (63.4% vs. 47.3%, OR, 1.68 [CI, 1.23-2.29]), and vaginal digitation (18.0% vs. 9.7%; OR, 2.18 [CI, 1.26-3.86]).
Obese patients were also more likely to have functional constipation (50.3%), compared with overweight (44.8%) and normal weight patients (41.1%).
There was a positive linear association between body mass index (BMI) and anal resting pressure (beta 0.45; R2, 0.25, P = 0.0003), though the odds of anal hypertension were not significantly higher after Benjamini-Hochberg correction. Obese patients more often had a large clinically significant rectocele (34.4% vs. 20.6%; OR, 2.62 [CI, 1.51-4.55]), compared with normal BMI patients.
The data showed higher rates of gynecological surgery, cholecystectomy, diabetes, and self-reported use of opioids, antidepressants, and anticholinergic medications in the obese group, compared with the others.
In morphological differences measured by x-ray defecography, obese patients had more than two-fold higher odds of having a rectocele and even greater odds of the rectocele being large and clinically significant. Anal and rectal resting pressures were linearly related to increasing BMI, the authors report.
Because most patients in the study were female, the findings may not be generalizable to the general population or male patients. Also, diet and exercise, two factors that may affect defecation disorders, were not accounted for in this study.
Dr. Chaichanavichkij reported no disclosures. Two other authors reported financial relationships with Medtronic Inc. and MMS/Laborie.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
Revised presentation of obesity may reduce internalized bias
a new study suggests.
In an online study, patients with obesity reported significantly less internalized weight bias and significantly enhanced perceptions of positive communication with their medical providers after watching a video of a doctor who framed obesity as a treatable medical condition, compared with a video of a doctor who emphasized willpower.
“Recent research has identified the dominant role that biology (both genetics as well as homeostatic, hedonic, and executive brain systems) and environment, rather than willpower, play in the development of obesity and the resistance to weight loss,” wrote study authors Sara English, a medical student, and Michael Vallis, MD, associate professor of family medicine, both at Dalhousie University, Halifax, N.S. “Yet the false narrative that ideal or goal weight can be achieved by eating less and moving more using willpower continues to dominate the public narrative.”
The findings were published in Clinical Obesity.
Medical complexity
The public discussion generally places all responsibility for the health outcomes of obesity on the patient. As a result, patients with obesity face bias and stigma from the public and the health care system, wrote the authors.
This stigmatization contributes to increased mortality and morbidity by promoting maladaptive eating behaviors and stress. It also causes mistrust of health care professionals, which, in turn, leads to worse health outcomes and increased health care costs.
The 2020 Canadian clinical practice guidelines for obesity management in adults emphasize that obesity is complex and that nonbehavioral factors strongly influence it. They recommend that treatment focus on improving patient-centered health outcomes and address the root causes of obesity, instead of focusing on weight loss alone.
In the present study, Ms. English and Dr. Vallis evaluated how presenting obesity as a treatable medical condition affected participants’ internalized weight bias and their perceived relationship with their health care provider. They asked 61 patients with obesity (average age, 49 years; average body mass index, 41 kg/m2) to watch two videos, the first showing a doctor endorsing the traditional “eat less, move more approach,” and the second showing a doctor describing obesity as a chronic, treatable medical condition.
Nearly half (49.5%) of participants reported that their health care provider rarely or never discusses weight loss, and almost two-thirds of participants (64%) reported feeling stigmatized by their health care provider because of their weight at least some of the time.
After having watched each video, participants were asked to imagine that they were being treated by the corresponding doctor and to complete two measures: the Weight Bias Internalization Scale (WBIS), which measures the degree to which a respondent believes the negative stereotypes about obese people, and the Patient-Health Care Provider Communication Scale (PHCPCS), which assesses the quality of patient–health care provider communication.
Virtually all participants preferred the care provider in the video with the revised presentation of obesity. Only one preferred the traditional video. The video with the revised presentation was associated with significant reductions in internalized weight bias. Participants’ WBIS total score decreased from 4.49 to 3.36 (P < .001). The revised narrative video also had a positive effect on patients’ perception of their health care providers. The PHCPCS total score increased from 2.65 to 4.20 (P < .001).
A chronic disease
In a comment, Yoni Freedhoff, MD, associate professor of family medicine at the University of Ottawa, said: “If you’re asking me if it is a good idea to treat obesity like a chronic disease, the answer would be yes, we absolutely should. It is a chronic disease, and it shouldn’t have a treatment paradigm different from the other chronic diseases.” Dr. Freedhoff did not participate in the study.
“We certainly don’t blame patients for having other chronic conditions,” Dr. Freedhoff added. “We don’t have a narrative that, in order for them to qualify for medication or other treatment options, they have to audition for them by failing lifestyle approaches first. And yet, I’d say at least 85% of chronic noncommunicable diseases have lifestyle factors, but obesity is the only one where we consider that there is a necessity for these lifestyle changes, as if there have been studies demonstrating durable and reproducible outcomes for lifestyle in obesity. There have not.”
Telling patients and doctors that obesity is a chronic disease driven by biology, not a failure of willpower, is going to reduce stigma, “which is what this study was able to demonstrate to some degree,” Dr. Freedhoff said.
“What is more stigmatizing? Being told that if you just try hard enough, you’ll succeed, and if you don’t succeed, the corollary, of course, is that you did not try hard enough? Versus, you’ve got a medical condition where you’ve got biological drivers beyond your locus of control, affecting behaviors that, in turn, contribute to your adiposity? I’m pretty sure the second statement will have far less impact on a person’s internalized weight bias than what we’ve unfortunately been doing up until now with the focus on willpower,” Dr. Freedhoff said.
No funding for the study was reported. Ms. English and Dr. Vallis reported no relevant financial relationships. Dr. Freedhoff reported receiving clinical grants from Novo Nordisk.
A version of this article first appeared on Medscape.com.
a new study suggests.
In an online study, patients with obesity reported significantly less internalized weight bias and significantly enhanced perceptions of positive communication with their medical providers after watching a video of a doctor who framed obesity as a treatable medical condition, compared with a video of a doctor who emphasized willpower.
“Recent research has identified the dominant role that biology (both genetics as well as homeostatic, hedonic, and executive brain systems) and environment, rather than willpower, play in the development of obesity and the resistance to weight loss,” wrote study authors Sara English, a medical student, and Michael Vallis, MD, associate professor of family medicine, both at Dalhousie University, Halifax, N.S. “Yet the false narrative that ideal or goal weight can be achieved by eating less and moving more using willpower continues to dominate the public narrative.”
The findings were published in Clinical Obesity.
Medical complexity
The public discussion generally places all responsibility for the health outcomes of obesity on the patient. As a result, patients with obesity face bias and stigma from the public and the health care system, wrote the authors.
This stigmatization contributes to increased mortality and morbidity by promoting maladaptive eating behaviors and stress. It also causes mistrust of health care professionals, which, in turn, leads to worse health outcomes and increased health care costs.
The 2020 Canadian clinical practice guidelines for obesity management in adults emphasize that obesity is complex and that nonbehavioral factors strongly influence it. They recommend that treatment focus on improving patient-centered health outcomes and address the root causes of obesity, instead of focusing on weight loss alone.
In the present study, Ms. English and Dr. Vallis evaluated how presenting obesity as a treatable medical condition affected participants’ internalized weight bias and their perceived relationship with their health care provider. They asked 61 patients with obesity (average age, 49 years; average body mass index, 41 kg/m2) to watch two videos, the first showing a doctor endorsing the traditional “eat less, move more approach,” and the second showing a doctor describing obesity as a chronic, treatable medical condition.
Nearly half (49.5%) of participants reported that their health care provider rarely or never discusses weight loss, and almost two-thirds of participants (64%) reported feeling stigmatized by their health care provider because of their weight at least some of the time.
After having watched each video, participants were asked to imagine that they were being treated by the corresponding doctor and to complete two measures: the Weight Bias Internalization Scale (WBIS), which measures the degree to which a respondent believes the negative stereotypes about obese people, and the Patient-Health Care Provider Communication Scale (PHCPCS), which assesses the quality of patient–health care provider communication.
Virtually all participants preferred the care provider in the video with the revised presentation of obesity. Only one preferred the traditional video. The video with the revised presentation was associated with significant reductions in internalized weight bias. Participants’ WBIS total score decreased from 4.49 to 3.36 (P < .001). The revised narrative video also had a positive effect on patients’ perception of their health care providers. The PHCPCS total score increased from 2.65 to 4.20 (P < .001).
A chronic disease
In a comment, Yoni Freedhoff, MD, associate professor of family medicine at the University of Ottawa, said: “If you’re asking me if it is a good idea to treat obesity like a chronic disease, the answer would be yes, we absolutely should. It is a chronic disease, and it shouldn’t have a treatment paradigm different from the other chronic diseases.” Dr. Freedhoff did not participate in the study.
“We certainly don’t blame patients for having other chronic conditions,” Dr. Freedhoff added. “We don’t have a narrative that, in order for them to qualify for medication or other treatment options, they have to audition for them by failing lifestyle approaches first. And yet, I’d say at least 85% of chronic noncommunicable diseases have lifestyle factors, but obesity is the only one where we consider that there is a necessity for these lifestyle changes, as if there have been studies demonstrating durable and reproducible outcomes for lifestyle in obesity. There have not.”
Telling patients and doctors that obesity is a chronic disease driven by biology, not a failure of willpower, is going to reduce stigma, “which is what this study was able to demonstrate to some degree,” Dr. Freedhoff said.
“What is more stigmatizing? Being told that if you just try hard enough, you’ll succeed, and if you don’t succeed, the corollary, of course, is that you did not try hard enough? Versus, you’ve got a medical condition where you’ve got biological drivers beyond your locus of control, affecting behaviors that, in turn, contribute to your adiposity? I’m pretty sure the second statement will have far less impact on a person’s internalized weight bias than what we’ve unfortunately been doing up until now with the focus on willpower,” Dr. Freedhoff said.
No funding for the study was reported. Ms. English and Dr. Vallis reported no relevant financial relationships. Dr. Freedhoff reported receiving clinical grants from Novo Nordisk.
A version of this article first appeared on Medscape.com.
a new study suggests.
In an online study, patients with obesity reported significantly less internalized weight bias and significantly enhanced perceptions of positive communication with their medical providers after watching a video of a doctor who framed obesity as a treatable medical condition, compared with a video of a doctor who emphasized willpower.
“Recent research has identified the dominant role that biology (both genetics as well as homeostatic, hedonic, and executive brain systems) and environment, rather than willpower, play in the development of obesity and the resistance to weight loss,” wrote study authors Sara English, a medical student, and Michael Vallis, MD, associate professor of family medicine, both at Dalhousie University, Halifax, N.S. “Yet the false narrative that ideal or goal weight can be achieved by eating less and moving more using willpower continues to dominate the public narrative.”
The findings were published in Clinical Obesity.
Medical complexity
The public discussion generally places all responsibility for the health outcomes of obesity on the patient. As a result, patients with obesity face bias and stigma from the public and the health care system, wrote the authors.
This stigmatization contributes to increased mortality and morbidity by promoting maladaptive eating behaviors and stress. It also causes mistrust of health care professionals, which, in turn, leads to worse health outcomes and increased health care costs.
The 2020 Canadian clinical practice guidelines for obesity management in adults emphasize that obesity is complex and that nonbehavioral factors strongly influence it. They recommend that treatment focus on improving patient-centered health outcomes and address the root causes of obesity, instead of focusing on weight loss alone.
In the present study, Ms. English and Dr. Vallis evaluated how presenting obesity as a treatable medical condition affected participants’ internalized weight bias and their perceived relationship with their health care provider. They asked 61 patients with obesity (average age, 49 years; average body mass index, 41 kg/m2) to watch two videos, the first showing a doctor endorsing the traditional “eat less, move more approach,” and the second showing a doctor describing obesity as a chronic, treatable medical condition.
Nearly half (49.5%) of participants reported that their health care provider rarely or never discusses weight loss, and almost two-thirds of participants (64%) reported feeling stigmatized by their health care provider because of their weight at least some of the time.
After having watched each video, participants were asked to imagine that they were being treated by the corresponding doctor and to complete two measures: the Weight Bias Internalization Scale (WBIS), which measures the degree to which a respondent believes the negative stereotypes about obese people, and the Patient-Health Care Provider Communication Scale (PHCPCS), which assesses the quality of patient–health care provider communication.
Virtually all participants preferred the care provider in the video with the revised presentation of obesity. Only one preferred the traditional video. The video with the revised presentation was associated with significant reductions in internalized weight bias. Participants’ WBIS total score decreased from 4.49 to 3.36 (P < .001). The revised narrative video also had a positive effect on patients’ perception of their health care providers. The PHCPCS total score increased from 2.65 to 4.20 (P < .001).
A chronic disease
In a comment, Yoni Freedhoff, MD, associate professor of family medicine at the University of Ottawa, said: “If you’re asking me if it is a good idea to treat obesity like a chronic disease, the answer would be yes, we absolutely should. It is a chronic disease, and it shouldn’t have a treatment paradigm different from the other chronic diseases.” Dr. Freedhoff did not participate in the study.
“We certainly don’t blame patients for having other chronic conditions,” Dr. Freedhoff added. “We don’t have a narrative that, in order for them to qualify for medication or other treatment options, they have to audition for them by failing lifestyle approaches first. And yet, I’d say at least 85% of chronic noncommunicable diseases have lifestyle factors, but obesity is the only one where we consider that there is a necessity for these lifestyle changes, as if there have been studies demonstrating durable and reproducible outcomes for lifestyle in obesity. There have not.”
Telling patients and doctors that obesity is a chronic disease driven by biology, not a failure of willpower, is going to reduce stigma, “which is what this study was able to demonstrate to some degree,” Dr. Freedhoff said.
“What is more stigmatizing? Being told that if you just try hard enough, you’ll succeed, and if you don’t succeed, the corollary, of course, is that you did not try hard enough? Versus, you’ve got a medical condition where you’ve got biological drivers beyond your locus of control, affecting behaviors that, in turn, contribute to your adiposity? I’m pretty sure the second statement will have far less impact on a person’s internalized weight bias than what we’ve unfortunately been doing up until now with the focus on willpower,” Dr. Freedhoff said.
No funding for the study was reported. Ms. English and Dr. Vallis reported no relevant financial relationships. Dr. Freedhoff reported receiving clinical grants from Novo Nordisk.
A version of this article first appeared on Medscape.com.
FROM CLINICAL OBESITY
Pain in upper right abdomen
The patient's history, symptomatology, and assessments suggest a diagnosis of nonalcoholic fatty liver disease (NAFLD). The primary care physician recommends referral to a hepatologist for evaluation and possible liver biopsy.
NAFLD involves an accumulation of triglycerides and other fats in the liver (unrelated to alcohol consumption and other liver disease), with the presence of hepatic steatosis in more than 5% of hepatocytes. NAFLD affects 25% to 35% of the general population, making it the most common cause of chronic liver disease. The rate increases among patients with obesity, 80% of whom are affected by NAFLD.
NAFLD should be considered in patients with unexplained elevations in serum aminotransferases (without positive viral markers or autoantibodies and no history of alcohol use) and a high risk for steatohepatitis, including obesity. The standard NAFLD assessment for biopsy specimens is the Brunt system, and disease stage is determined using the NAFLD activity score and the amount of fibrosis present.
A study of the natural history of NAFLD in patients who were followed for 3 years showed that without pharmacologic intervention, one third experienced disease progression, one third remained stable, and one third improved. An independent risk factor for progression of nonalcoholic steatohepatitis was abnormal glucose tolerance testing. In another natural history study, a 10% higher rate of mortality over 10 years was demonstrated among those with NAFLD vs controls, with the top three causes of death being cancer, heart disease, and liver-related disease. Prevalence of chronic liver disease and cirrhosis has been shown to be elevated in Latino and Japanese American populations.
Patients with NAFLD should be seen regularly to assess for disease progression and receive guidance on weight management interventions and exercise. A weight loss of more than 5% has been shown to reduce liver fat and provide cardiometabolic benefits; a weight reduction of more than 10% can help reverse steatohepatitis or liver fibrosis. In addition to weight loss management strategies, physicians should discuss the importance of controlling hyperlipidemia, insulin resistance, and T2D with their patients and share the importance of avoiding alcohol and other hepatotoxic substances.
According to the American Association of Clinical Endocrinology Clinical Practice Guideline: "There are no U.S. Food and Drug Administration-approved medications for the treatment of NAFLD; however, some diabetes and anti-obesity medications can be beneficial. Bariatric surgery is also effective for weight loss and reducing liver fat in persons with severe obesity."
Courtney Whittle, MD, MSW, Diplomate of ABOM, Pediatric Lead, Obesity Champion, TSPMG, Weight A Minute Clinic, Atlanta, Georgia.
Courtney Whittle, MD, MSW, Diplomate of ABOM, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
The patient's history, symptomatology, and assessments suggest a diagnosis of nonalcoholic fatty liver disease (NAFLD). The primary care physician recommends referral to a hepatologist for evaluation and possible liver biopsy.
NAFLD involves an accumulation of triglycerides and other fats in the liver (unrelated to alcohol consumption and other liver disease), with the presence of hepatic steatosis in more than 5% of hepatocytes. NAFLD affects 25% to 35% of the general population, making it the most common cause of chronic liver disease. The rate increases among patients with obesity, 80% of whom are affected by NAFLD.
NAFLD should be considered in patients with unexplained elevations in serum aminotransferases (without positive viral markers or autoantibodies and no history of alcohol use) and a high risk for steatohepatitis, including obesity. The standard NAFLD assessment for biopsy specimens is the Brunt system, and disease stage is determined using the NAFLD activity score and the amount of fibrosis present.
A study of the natural history of NAFLD in patients who were followed for 3 years showed that without pharmacologic intervention, one third experienced disease progression, one third remained stable, and one third improved. An independent risk factor for progression of nonalcoholic steatohepatitis was abnormal glucose tolerance testing. In another natural history study, a 10% higher rate of mortality over 10 years was demonstrated among those with NAFLD vs controls, with the top three causes of death being cancer, heart disease, and liver-related disease. Prevalence of chronic liver disease and cirrhosis has been shown to be elevated in Latino and Japanese American populations.
Patients with NAFLD should be seen regularly to assess for disease progression and receive guidance on weight management interventions and exercise. A weight loss of more than 5% has been shown to reduce liver fat and provide cardiometabolic benefits; a weight reduction of more than 10% can help reverse steatohepatitis or liver fibrosis. In addition to weight loss management strategies, physicians should discuss the importance of controlling hyperlipidemia, insulin resistance, and T2D with their patients and share the importance of avoiding alcohol and other hepatotoxic substances.
According to the American Association of Clinical Endocrinology Clinical Practice Guideline: "There are no U.S. Food and Drug Administration-approved medications for the treatment of NAFLD; however, some diabetes and anti-obesity medications can be beneficial. Bariatric surgery is also effective for weight loss and reducing liver fat in persons with severe obesity."
Courtney Whittle, MD, MSW, Diplomate of ABOM, Pediatric Lead, Obesity Champion, TSPMG, Weight A Minute Clinic, Atlanta, Georgia.
Courtney Whittle, MD, MSW, Diplomate of ABOM, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
The patient's history, symptomatology, and assessments suggest a diagnosis of nonalcoholic fatty liver disease (NAFLD). The primary care physician recommends referral to a hepatologist for evaluation and possible liver biopsy.
NAFLD involves an accumulation of triglycerides and other fats in the liver (unrelated to alcohol consumption and other liver disease), with the presence of hepatic steatosis in more than 5% of hepatocytes. NAFLD affects 25% to 35% of the general population, making it the most common cause of chronic liver disease. The rate increases among patients with obesity, 80% of whom are affected by NAFLD.
NAFLD should be considered in patients with unexplained elevations in serum aminotransferases (without positive viral markers or autoantibodies and no history of alcohol use) and a high risk for steatohepatitis, including obesity. The standard NAFLD assessment for biopsy specimens is the Brunt system, and disease stage is determined using the NAFLD activity score and the amount of fibrosis present.
A study of the natural history of NAFLD in patients who were followed for 3 years showed that without pharmacologic intervention, one third experienced disease progression, one third remained stable, and one third improved. An independent risk factor for progression of nonalcoholic steatohepatitis was abnormal glucose tolerance testing. In another natural history study, a 10% higher rate of mortality over 10 years was demonstrated among those with NAFLD vs controls, with the top three causes of death being cancer, heart disease, and liver-related disease. Prevalence of chronic liver disease and cirrhosis has been shown to be elevated in Latino and Japanese American populations.
Patients with NAFLD should be seen regularly to assess for disease progression and receive guidance on weight management interventions and exercise. A weight loss of more than 5% has been shown to reduce liver fat and provide cardiometabolic benefits; a weight reduction of more than 10% can help reverse steatohepatitis or liver fibrosis. In addition to weight loss management strategies, physicians should discuss the importance of controlling hyperlipidemia, insulin resistance, and T2D with their patients and share the importance of avoiding alcohol and other hepatotoxic substances.
According to the American Association of Clinical Endocrinology Clinical Practice Guideline: "There are no U.S. Food and Drug Administration-approved medications for the treatment of NAFLD; however, some diabetes and anti-obesity medications can be beneficial. Bariatric surgery is also effective for weight loss and reducing liver fat in persons with severe obesity."
Courtney Whittle, MD, MSW, Diplomate of ABOM, Pediatric Lead, Obesity Champion, TSPMG, Weight A Minute Clinic, Atlanta, Georgia.
Courtney Whittle, MD, MSW, Diplomate of ABOM, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
A 51-year-old Hispanic man presents to his primary care physician with fatigue and pain in the upper right abdomen. Physical exam reveals ascites and splenomegaly. His height is 5 ft 8 in and weight is 274 lb; his BMI is 41.7. For the past 5 years, the patient has seen his physician for routine annual exams, during which time he has consistently met the criteria for World Health Organization Class 3 overweight (BMI ≥ 40) and has taken metformin, with varying degrees of adherence, for type 2 diabetes (T2D). Now, given the patient's symptoms and the potential for uncontrolled diabetes, the physician orders laboratory studies and viral serologies for hepatitis. Results of these assessments exclude viral infection but demonstrate abnormal levels of fasting insulin and glucose, hypertriglyceridemia, and elevated transaminase levels that are sixfold above normal levels, with an aspartate aminotransferase-to-alanine transaminase ratio < 1:1.
‘Triple G’ agonist hits new weight loss heights
A novel triple agonist to receptors for three nutrient-stimulated hormones led to weight loss as high as 24% among people with overweight or obesity but who did not have type 2 diabetes when used at the highest tested dose for 48 weeks. The results are from a phase 2 study of retatrutide that was published in The New England Journal of Medicine (2023 Aug 10. doi: 10.1056/NEJMoa2301972).
This level of weight loss is “unprecedented” for a medication administered for 48 weeks, Mary-Elizabeth Patti, MD, said in an editorial that accompanied the report.
The findings “offer further optimism ... that effective pharmacologic management of obesity and related disorders is possible,” wrote Dr. Patti, a principal investigator at the Joslin Diabetes Center in Boston.
The study randomly assigned 338 adults with obesity or overweight – a body mass index (BMI) of ≥ 27 kg/m2 – and at least one weight-related complication to receive either weekly subcutaneous injections of retatrutide in any of six dose regimens or placebo over 48 weeks. The primary outcome was weight change from baseline after 24 weeks.
The highest dose of retatrutide safely produced an average 17.5% drop from baseline weight, compared with an average 1.6% reduction in the placebo group, after 24 weeks, a significant difference.
After 48 weeks, the highest retatrutide dose safely cut baseline weight by an average of 24.2%, compared with an average 2.1% drop among placebo control patients, Ania M. Jastreboff, MD, PhD, and her coauthors wrote in their report. Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-response pattern.
Weight losses never before seen
“I have never seen weight loss at this level” after nearly 1 year of treatment, Dr. Jastreboff said when she discussed these findings in a press conference at the annual scientific sessions of the American Diabetes Association in San Diego in late June.
A separate presentation at the ADA meeting documented unprecedented weight loss levels in a study of 281 people with obesity or overweight and type 2 diabetes.
“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who formally presented the results from the study of retatrutide in people with type 2 diabetes at the ADA meeting.
The mechanism behind retatrutide’s potent weight-loss effect seems likely tied to its action on three human receptors that naturally respond to three nutrient-stimulated hormones that control appetite, metabolism, fat mobilization, and related functions.
The three hormones that the retatrutide molecule simultaneously mimics are glucagon-like peptide-1 (GLP-1), such as agents in the class of GLP-1 agonists that includes liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy); the glucose-dependent insulinotropic polypeptide (GIP), the receptor that is also activated by tirzepatide (Mounjaro), a dual-incretin receptor agonist that mimics both GLP-1 and GIP; and glucagon. Survodutide is a dual GLP-1 and glucagon receptor agonist in phase 2 development.
Retatrutide is currently unique among agents with reported clinical results by having agonist effects on the receptors for all three of these hormones, a property that led Dr. Patti to call retatrutide a “triple G” hormone-receptor agonist in her editorial.
Triple agonist has added effect on liver fat clearance
The glucagon-receptor agonism appears to give retatrutide added effects beyond those of the GLP-1 agonists or GLP-1/GIP dual agonists that are increasingly used in U.S. practice.
A prespecified subgroup analysis of the no diabetes/Jastreboff study (but that was not included in the NEJM report) showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those whose liver volume was at least 10% fat at study entry).
That percentage increased to about 90% of people receiving these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the ADA meeting.
“When you add glucagon activity, liver-fat clearance goes up tremendously,” observed Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.
The average age of the participants in the new study of the use of retatrutide for those with obesity/overweight but not diabetes was 48 years. By design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m2.
Treatment with retatrutide was also significantly associated with improvements in several cardiometabolic measures in exploratory analyses, including systolic and diastolic blood pressure, A1c, fasting glucose, insulin, and some (but not all) lipids, Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn., and her coauthors reported in the NEJM article.
The safety profile of retatrutide was consistent with reported phase 1 findings for the agent among people with type 2 diabetes and resembled the safety profiles of other agents based on GLP-1 or GIP–GLP-1 mimicry for the treatment of type 2 diabetes or obesity.
The most frequently reported adverse events from retatrutide were transient, mostly mild to moderate gastrointestinal events. They occurred primarily during dose escalation. Discontinuation of retatrutide or placebo because of adverse events occurred in 6% to 16% of the participants who received retatrutide and in none of the participants who received placebo.
Lilly, the company developing retatrutide, previously announced the launch of four phase 3 trials to gather further data on retatrutide for use in a marketing-approval application to the Food and Drug Administration.
The four trials – TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 – are evaluating the safety and efficacy of retatrutide for chronic weight management for those with obesity or overweight, including those who also have obstructive sleep apnea, knee osteoarthritis, type 2 diabetes, or cardiovascular disease.
The study was sponsored by Lilly, the company developing retatrutide. Dr. Patti has been a consultant to AstraZeneca, Dexcom, Hanmi, and MBX. She has received funding from Dexcom and has been a monitor for a trial funded by Fractyl. Dr. Jastreboff, Dr. Kaplan, and Dr. Rosenstock have reported financial relationships with Lilly as well as other companies.
A version of this article first appeared on Medscape.com.
A novel triple agonist to receptors for three nutrient-stimulated hormones led to weight loss as high as 24% among people with overweight or obesity but who did not have type 2 diabetes when used at the highest tested dose for 48 weeks. The results are from a phase 2 study of retatrutide that was published in The New England Journal of Medicine (2023 Aug 10. doi: 10.1056/NEJMoa2301972).
This level of weight loss is “unprecedented” for a medication administered for 48 weeks, Mary-Elizabeth Patti, MD, said in an editorial that accompanied the report.
The findings “offer further optimism ... that effective pharmacologic management of obesity and related disorders is possible,” wrote Dr. Patti, a principal investigator at the Joslin Diabetes Center in Boston.
The study randomly assigned 338 adults with obesity or overweight – a body mass index (BMI) of ≥ 27 kg/m2 – and at least one weight-related complication to receive either weekly subcutaneous injections of retatrutide in any of six dose regimens or placebo over 48 weeks. The primary outcome was weight change from baseline after 24 weeks.
The highest dose of retatrutide safely produced an average 17.5% drop from baseline weight, compared with an average 1.6% reduction in the placebo group, after 24 weeks, a significant difference.
After 48 weeks, the highest retatrutide dose safely cut baseline weight by an average of 24.2%, compared with an average 2.1% drop among placebo control patients, Ania M. Jastreboff, MD, PhD, and her coauthors wrote in their report. Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-response pattern.
Weight losses never before seen
“I have never seen weight loss at this level” after nearly 1 year of treatment, Dr. Jastreboff said when she discussed these findings in a press conference at the annual scientific sessions of the American Diabetes Association in San Diego in late June.
A separate presentation at the ADA meeting documented unprecedented weight loss levels in a study of 281 people with obesity or overweight and type 2 diabetes.
“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who formally presented the results from the study of retatrutide in people with type 2 diabetes at the ADA meeting.
The mechanism behind retatrutide’s potent weight-loss effect seems likely tied to its action on three human receptors that naturally respond to three nutrient-stimulated hormones that control appetite, metabolism, fat mobilization, and related functions.
The three hormones that the retatrutide molecule simultaneously mimics are glucagon-like peptide-1 (GLP-1), such as agents in the class of GLP-1 agonists that includes liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy); the glucose-dependent insulinotropic polypeptide (GIP), the receptor that is also activated by tirzepatide (Mounjaro), a dual-incretin receptor agonist that mimics both GLP-1 and GIP; and glucagon. Survodutide is a dual GLP-1 and glucagon receptor agonist in phase 2 development.
Retatrutide is currently unique among agents with reported clinical results by having agonist effects on the receptors for all three of these hormones, a property that led Dr. Patti to call retatrutide a “triple G” hormone-receptor agonist in her editorial.
Triple agonist has added effect on liver fat clearance
The glucagon-receptor agonism appears to give retatrutide added effects beyond those of the GLP-1 agonists or GLP-1/GIP dual agonists that are increasingly used in U.S. practice.
A prespecified subgroup analysis of the no diabetes/Jastreboff study (but that was not included in the NEJM report) showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those whose liver volume was at least 10% fat at study entry).
That percentage increased to about 90% of people receiving these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the ADA meeting.
“When you add glucagon activity, liver-fat clearance goes up tremendously,” observed Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.
The average age of the participants in the new study of the use of retatrutide for those with obesity/overweight but not diabetes was 48 years. By design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m2.
Treatment with retatrutide was also significantly associated with improvements in several cardiometabolic measures in exploratory analyses, including systolic and diastolic blood pressure, A1c, fasting glucose, insulin, and some (but not all) lipids, Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn., and her coauthors reported in the NEJM article.
The safety profile of retatrutide was consistent with reported phase 1 findings for the agent among people with type 2 diabetes and resembled the safety profiles of other agents based on GLP-1 or GIP–GLP-1 mimicry for the treatment of type 2 diabetes or obesity.
The most frequently reported adverse events from retatrutide were transient, mostly mild to moderate gastrointestinal events. They occurred primarily during dose escalation. Discontinuation of retatrutide or placebo because of adverse events occurred in 6% to 16% of the participants who received retatrutide and in none of the participants who received placebo.
Lilly, the company developing retatrutide, previously announced the launch of four phase 3 trials to gather further data on retatrutide for use in a marketing-approval application to the Food and Drug Administration.
The four trials – TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 – are evaluating the safety and efficacy of retatrutide for chronic weight management for those with obesity or overweight, including those who also have obstructive sleep apnea, knee osteoarthritis, type 2 diabetes, or cardiovascular disease.
The study was sponsored by Lilly, the company developing retatrutide. Dr. Patti has been a consultant to AstraZeneca, Dexcom, Hanmi, and MBX. She has received funding from Dexcom and has been a monitor for a trial funded by Fractyl. Dr. Jastreboff, Dr. Kaplan, and Dr. Rosenstock have reported financial relationships with Lilly as well as other companies.
A version of this article first appeared on Medscape.com.
A novel triple agonist to receptors for three nutrient-stimulated hormones led to weight loss as high as 24% among people with overweight or obesity but who did not have type 2 diabetes when used at the highest tested dose for 48 weeks. The results are from a phase 2 study of retatrutide that was published in The New England Journal of Medicine (2023 Aug 10. doi: 10.1056/NEJMoa2301972).
This level of weight loss is “unprecedented” for a medication administered for 48 weeks, Mary-Elizabeth Patti, MD, said in an editorial that accompanied the report.
The findings “offer further optimism ... that effective pharmacologic management of obesity and related disorders is possible,” wrote Dr. Patti, a principal investigator at the Joslin Diabetes Center in Boston.
The study randomly assigned 338 adults with obesity or overweight – a body mass index (BMI) of ≥ 27 kg/m2 – and at least one weight-related complication to receive either weekly subcutaneous injections of retatrutide in any of six dose regimens or placebo over 48 weeks. The primary outcome was weight change from baseline after 24 weeks.
The highest dose of retatrutide safely produced an average 17.5% drop from baseline weight, compared with an average 1.6% reduction in the placebo group, after 24 weeks, a significant difference.
After 48 weeks, the highest retatrutide dose safely cut baseline weight by an average of 24.2%, compared with an average 2.1% drop among placebo control patients, Ania M. Jastreboff, MD, PhD, and her coauthors wrote in their report. Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-response pattern.
Weight losses never before seen
“I have never seen weight loss at this level” after nearly 1 year of treatment, Dr. Jastreboff said when she discussed these findings in a press conference at the annual scientific sessions of the American Diabetes Association in San Diego in late June.
A separate presentation at the ADA meeting documented unprecedented weight loss levels in a study of 281 people with obesity or overweight and type 2 diabetes.
“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who formally presented the results from the study of retatrutide in people with type 2 diabetes at the ADA meeting.
The mechanism behind retatrutide’s potent weight-loss effect seems likely tied to its action on three human receptors that naturally respond to three nutrient-stimulated hormones that control appetite, metabolism, fat mobilization, and related functions.
The three hormones that the retatrutide molecule simultaneously mimics are glucagon-like peptide-1 (GLP-1), such as agents in the class of GLP-1 agonists that includes liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy); the glucose-dependent insulinotropic polypeptide (GIP), the receptor that is also activated by tirzepatide (Mounjaro), a dual-incretin receptor agonist that mimics both GLP-1 and GIP; and glucagon. Survodutide is a dual GLP-1 and glucagon receptor agonist in phase 2 development.
Retatrutide is currently unique among agents with reported clinical results by having agonist effects on the receptors for all three of these hormones, a property that led Dr. Patti to call retatrutide a “triple G” hormone-receptor agonist in her editorial.
Triple agonist has added effect on liver fat clearance
The glucagon-receptor agonism appears to give retatrutide added effects beyond those of the GLP-1 agonists or GLP-1/GIP dual agonists that are increasingly used in U.S. practice.
A prespecified subgroup analysis of the no diabetes/Jastreboff study (but that was not included in the NEJM report) showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those whose liver volume was at least 10% fat at study entry).
That percentage increased to about 90% of people receiving these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the ADA meeting.
“When you add glucagon activity, liver-fat clearance goes up tremendously,” observed Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.
The average age of the participants in the new study of the use of retatrutide for those with obesity/overweight but not diabetes was 48 years. By design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m2.
Treatment with retatrutide was also significantly associated with improvements in several cardiometabolic measures in exploratory analyses, including systolic and diastolic blood pressure, A1c, fasting glucose, insulin, and some (but not all) lipids, Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn., and her coauthors reported in the NEJM article.
The safety profile of retatrutide was consistent with reported phase 1 findings for the agent among people with type 2 diabetes and resembled the safety profiles of other agents based on GLP-1 or GIP–GLP-1 mimicry for the treatment of type 2 diabetes or obesity.
The most frequently reported adverse events from retatrutide were transient, mostly mild to moderate gastrointestinal events. They occurred primarily during dose escalation. Discontinuation of retatrutide or placebo because of adverse events occurred in 6% to 16% of the participants who received retatrutide and in none of the participants who received placebo.
Lilly, the company developing retatrutide, previously announced the launch of four phase 3 trials to gather further data on retatrutide for use in a marketing-approval application to the Food and Drug Administration.
The four trials – TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 – are evaluating the safety and efficacy of retatrutide for chronic weight management for those with obesity or overweight, including those who also have obstructive sleep apnea, knee osteoarthritis, type 2 diabetes, or cardiovascular disease.
The study was sponsored by Lilly, the company developing retatrutide. Dr. Patti has been a consultant to AstraZeneca, Dexcom, Hanmi, and MBX. She has received funding from Dexcom and has been a monitor for a trial funded by Fractyl. Dr. Jastreboff, Dr. Kaplan, and Dr. Rosenstock have reported financial relationships with Lilly as well as other companies.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
How newly discovered genes might fit into obesity
Identifying specific genes adds to growing evidence that biology, in part, drives obesity. Researchers hope the findings will lead to effective treatments, and in the meantime add to the understanding that there are many types of obesity that come from a mix of genes and environmental factors.
Although the study is not the first to point to specific genes, “we were quite surprised by the proposed function of some of the genes we identified,” Lena R. Kaisinger, lead study investigator and a PhD student in the MRC Epidemiology Unit at the University of Cambridge (England), wrote in an email. For example, the genes also manage cell death and influence how cells respond to DNA damage.
The investigators are not sure why genes involved in body size perform this kind of double duty, which opens avenues for future research.
The gene sequencing study was published online in the journal Cell Genomics.
Differences between women and men
The researchers found five new genes in females and two new genes in males linked to greater body mass index (BMI): DIDO1, KIAA1109, MC4R, PTPRG and SLC12A5 in women and MC4R and SLTM in men. People who recall having obesity as a child were more likely to have rare genetic changes in two other genes, OBSCN and MADD.
“The key thing is that when you see real genes with real gene names, it really makes real the notion that genetics underlie obesity,” said Lee Kaplan, MD, PhD, director of the Obesity and Metabolism Institute in Boston, who was not affiliated with the research.
Ms. Kaisinger and colleagues found these significant genetic differences by studying genomes of about 420,000 people stored in the UK Biobank, a huge biomedical database. The researchers decided to look at genes by sex and age because these are “two areas that we still know very little about,” Ms. Kaisinger said.
“We know that different types of obesity connect to different ages,” said Dr. Kaplan, who is also past president of the Obesity Society. “But what they’ve done now is find genes that are associated with particular subtypes of obesity ... some more common in one sex and some more common in different phases of life, including early onset obesity.”
The future is already here
Treatment for obesity based on a person’s genes already exists. For example, in June 2022, the Food and Drug Administration approved setmelanotide (Imcivree) for weight management in adults and children aged over 6 years with specific genetic markers.
Even as encouraging as setmelanotide is to Ms. Kaisinger and colleagues, these are still early days for translating the current research findings into clinical obesity tests and potential treatment, she said.
The “holy grail,” Dr. Kaplan said, is a future where people get screened for a particular genetic profile and their provider can say something like, “You’re probably most susceptible to this type, so we’ll treat you with this particular drug that’s been developed for people with this phenotype.”
Dr. Kaplan added: “That’s exactly what we are trying to do.”
Moving forward, Ms. Kaisinger and colleagues plan to repeat the study in larger and more diverse populations. They also plan to reverse the usual road map for studies, which typically start in animals and then progress to humans.
“We plan to take the most promising gene candidates forward into mouse models to learn more about their function and how exactly their dysfunction results in obesity,” Ms. Kaisinger said.
Three study coauthors are employees and shareholders of Adrestia Therapeutics. No other conflicts of interest were reported.
A version of this article appeared on WebMD.com.
Identifying specific genes adds to growing evidence that biology, in part, drives obesity. Researchers hope the findings will lead to effective treatments, and in the meantime add to the understanding that there are many types of obesity that come from a mix of genes and environmental factors.
Although the study is not the first to point to specific genes, “we were quite surprised by the proposed function of some of the genes we identified,” Lena R. Kaisinger, lead study investigator and a PhD student in the MRC Epidemiology Unit at the University of Cambridge (England), wrote in an email. For example, the genes also manage cell death and influence how cells respond to DNA damage.
The investigators are not sure why genes involved in body size perform this kind of double duty, which opens avenues for future research.
The gene sequencing study was published online in the journal Cell Genomics.
Differences between women and men
The researchers found five new genes in females and two new genes in males linked to greater body mass index (BMI): DIDO1, KIAA1109, MC4R, PTPRG and SLC12A5 in women and MC4R and SLTM in men. People who recall having obesity as a child were more likely to have rare genetic changes in two other genes, OBSCN and MADD.
“The key thing is that when you see real genes with real gene names, it really makes real the notion that genetics underlie obesity,” said Lee Kaplan, MD, PhD, director of the Obesity and Metabolism Institute in Boston, who was not affiliated with the research.
Ms. Kaisinger and colleagues found these significant genetic differences by studying genomes of about 420,000 people stored in the UK Biobank, a huge biomedical database. The researchers decided to look at genes by sex and age because these are “two areas that we still know very little about,” Ms. Kaisinger said.
“We know that different types of obesity connect to different ages,” said Dr. Kaplan, who is also past president of the Obesity Society. “But what they’ve done now is find genes that are associated with particular subtypes of obesity ... some more common in one sex and some more common in different phases of life, including early onset obesity.”
The future is already here
Treatment for obesity based on a person’s genes already exists. For example, in June 2022, the Food and Drug Administration approved setmelanotide (Imcivree) for weight management in adults and children aged over 6 years with specific genetic markers.
Even as encouraging as setmelanotide is to Ms. Kaisinger and colleagues, these are still early days for translating the current research findings into clinical obesity tests and potential treatment, she said.
The “holy grail,” Dr. Kaplan said, is a future where people get screened for a particular genetic profile and their provider can say something like, “You’re probably most susceptible to this type, so we’ll treat you with this particular drug that’s been developed for people with this phenotype.”
Dr. Kaplan added: “That’s exactly what we are trying to do.”
Moving forward, Ms. Kaisinger and colleagues plan to repeat the study in larger and more diverse populations. They also plan to reverse the usual road map for studies, which typically start in animals and then progress to humans.
“We plan to take the most promising gene candidates forward into mouse models to learn more about their function and how exactly their dysfunction results in obesity,” Ms. Kaisinger said.
Three study coauthors are employees and shareholders of Adrestia Therapeutics. No other conflicts of interest were reported.
A version of this article appeared on WebMD.com.
Identifying specific genes adds to growing evidence that biology, in part, drives obesity. Researchers hope the findings will lead to effective treatments, and in the meantime add to the understanding that there are many types of obesity that come from a mix of genes and environmental factors.
Although the study is not the first to point to specific genes, “we were quite surprised by the proposed function of some of the genes we identified,” Lena R. Kaisinger, lead study investigator and a PhD student in the MRC Epidemiology Unit at the University of Cambridge (England), wrote in an email. For example, the genes also manage cell death and influence how cells respond to DNA damage.
The investigators are not sure why genes involved in body size perform this kind of double duty, which opens avenues for future research.
The gene sequencing study was published online in the journal Cell Genomics.
Differences between women and men
The researchers found five new genes in females and two new genes in males linked to greater body mass index (BMI): DIDO1, KIAA1109, MC4R, PTPRG and SLC12A5 in women and MC4R and SLTM in men. People who recall having obesity as a child were more likely to have rare genetic changes in two other genes, OBSCN and MADD.
“The key thing is that when you see real genes with real gene names, it really makes real the notion that genetics underlie obesity,” said Lee Kaplan, MD, PhD, director of the Obesity and Metabolism Institute in Boston, who was not affiliated with the research.
Ms. Kaisinger and colleagues found these significant genetic differences by studying genomes of about 420,000 people stored in the UK Biobank, a huge biomedical database. The researchers decided to look at genes by sex and age because these are “two areas that we still know very little about,” Ms. Kaisinger said.
“We know that different types of obesity connect to different ages,” said Dr. Kaplan, who is also past president of the Obesity Society. “But what they’ve done now is find genes that are associated with particular subtypes of obesity ... some more common in one sex and some more common in different phases of life, including early onset obesity.”
The future is already here
Treatment for obesity based on a person’s genes already exists. For example, in June 2022, the Food and Drug Administration approved setmelanotide (Imcivree) for weight management in adults and children aged over 6 years with specific genetic markers.
Even as encouraging as setmelanotide is to Ms. Kaisinger and colleagues, these are still early days for translating the current research findings into clinical obesity tests and potential treatment, she said.
The “holy grail,” Dr. Kaplan said, is a future where people get screened for a particular genetic profile and their provider can say something like, “You’re probably most susceptible to this type, so we’ll treat you with this particular drug that’s been developed for people with this phenotype.”
Dr. Kaplan added: “That’s exactly what we are trying to do.”
Moving forward, Ms. Kaisinger and colleagues plan to repeat the study in larger and more diverse populations. They also plan to reverse the usual road map for studies, which typically start in animals and then progress to humans.
“We plan to take the most promising gene candidates forward into mouse models to learn more about their function and how exactly their dysfunction results in obesity,” Ms. Kaisinger said.
Three study coauthors are employees and shareholders of Adrestia Therapeutics. No other conflicts of interest were reported.
A version of this article appeared on WebMD.com.
FROM CELL GENOMICS