Obesity

MADRID — The role of vitamin D in the risk for overweight and obesity has been the subject of multiple studies. Though there’s still not enough evidence to reach a decisive conclusion, several ongoing debates are setting the stage for future research.

Irene Bretón, MD, PhD, discussed these debates in a presentation titled “Vitamin D Deficiency and Obesity: Cause or Consequence?” delivered at the 64th Congress of the Spanish Society of Endocrinology and Nutrition (SEEN). Dr. Bretón is president of the Foundation of the Spanish Society of Endocrinology and Nutrition.

“Vitamin D deficiency can arise from different causes. The percentage that can be attributed to solar radiation is extremely variable. Some studies put it at 80%, while others suggest lower figures. Many diseases have also been associated with vitamin D deficiency or with low vitamin D levels (which are not always at the level of deficiency). Nonetheless, we still have a lot to learn about these associations,” she said.

Dr. Bretón pointed out that many of these studies overlook parathyroid hormone testing. “I also think it’s more appropriate to discuss nutritional status of vitamin D as opposed to serum levels, because these data can be misleading. It would be interesting to focus more on vitamin D metabolism and not just plasma levels.”
 

Vitamin Deficiency 

To answer whether obesity and its complications could be related to low vitamin D levels, Dr. Bretón pointed to this vitamin’s profile in various regions of the world and called attention to the fact that none of the studies on this topic include populations with roughly adequate levels of this vitamin.

“This highlights the prevalence of vitamin D deficiency worldwide. It affects approximately 50% of the population, has been described in all age groups, and affects both men and women — particularly pregnant women and those in menopause — and older adults,” said Dr. Bretón.

She also cited the figures backing this fact: 88% have 25-hydroxyvitamin D levels < 30 ng/mL, 37% have levels < 20 ng/mL, and 7% have levels < 10 ng/mL.

“These percentages have brought us to consider their potential link to the current obesity epidemic. Studies in humans have observed a relationship between low plasma levels and markers for obesity and adiposity. Free 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D are known to be reduced in obesity, and treatments to correct vitamin D deficiency are less effective in people with the disease,” she noted.

Regarding the impact in “the opposite direction,” that is, whether obesity affects the nutritional status of vitamin D, Bretón explained that observational studies have generally found a relationship between overweight and obesity and lower plasma levels of vitamin D. “Data from these studies show that each kg/m² increase in [body mass index (BMI)] is associated with a 1.15% decrease in 25-hydroxyvitamin D. These studies also show that the prevalence of vitamin D deficiency is 35% higher in patients with obesity and 24% higher in those that are overweight compared with individuals of normal weight. A relationship has been observed between vitamin D deficiency and body fat percentage in men and women and in all age groups,” explained Dr. Bretón.

Dr. Bretón noted that the diseases most closely associated with obesity are type 2 diabetes, hypertension, ischemic heart disease, cancer (colon, breast, prostate, and ovarian), inflammatory liver disease, asthma, and inflammatory diseases.
 

Mechanisms Involved

Dr. Bretón reviewed the latest evidence on the mechanisms involved in the relationship between obesity and vitamin D deficiency. “People with obesity may experience less solar exposure (more of their body is covered, or they spend more time indoors), but reduced exposure to the sun is known to have less of an influence on vitamin D levels. Studies where people were given radiation to test how their plasma levels of vitamin D respond have found that there is a smaller effect in people with obesity, and that the effect is inversely correlated with BMI: the higher the BMI, the less vitamin D levels increase under exposure to solar radiation.”

Another mechanism is sequestration in adipose tissue, which is the largest reservoir of vitamin D in the body. Nevertheless, factors such as vitamin D concentration in this tissue, regulation of local metabolism, and vitamin uptake and release are less understood. It is therefore unclear whether this mechanism acts to regulate plasma levels.

“This is why severe vitamin D deficiencies (and deficiencies of other fat-soluble vitamins) that occur after bariatric surgery are often not seen in the first year after surgery but develop much later, when the vitamin that has accumulated in adipose tissue is released as weight is lost,” said Dr. Bretón.

“On the other hand, the volumetric dilution in blood that occurs in relation to total body fat content may explain the variability of plasma levels and the response to treatment. Predictive equations have been described,” she explained.
 

The Prenatal Stage

Dr. Bretón mentioned that the best setting for studying the impact of vitamin D and preventing future obesity is during the initial stages of life, when adipogenesis and fetal programming are occurring.

“Studies in animals have shown how maternal vitamin D deficiency (due to nongenetic or nonepigenetic mechanisms) leads to changes in adipogenesis and programming of adipose reserves. A fetal or perinatal environment with low vitamin D levels programs all these mechanisms differently, and not just adipogenesis and adipocyte differentiation in utero,” she added.

Various mechanisms involved in vitamin D deficiency as a cause of obesity are currently being studied in the prenatal setting. One such mechanism is the interaction between the vitamin D receptor and 1 alpha–hydroxylase, which are present in the adipose tissue and help modulate lipid metabolism.

“The vitamin D receptor is particularly expressed in the early stages of adipocyte differentiation, but its expression drops off as the differentiation process continues. Vitamin D receptor knockout mice have a slender phenotype and are resistant to diet-induced obesity. They also accumulate less fat with age and a high-fat diet,” explained Dr. Bretón.

“However, vitamin D also influences the production of inflammatory adipokines in these early stages of life. It specifically plays a central role in modulating the inflammatory response in adipose tissue. These anti-inflammatory effects appear to be mediated by inhibition of [NF–kappa B] and MAPK signaling pathways. All of this suggests that vitamin D influences both adipogenesis and how the adipose tissue functions,” she added.
 

Weight Loss 

When considering the link between vitamin D and obesity in the context of weight loss, Dr. Bretón explained that studies in this area suggest that weight loss per se is not sufficient to increase serum 25-hydroxyvitamin D. Rather, increased synthesis by the skin or increased dietary intake are the most relevant factors for the nutritional status of this vitamin.

“A recent systematic review looking at the relationship between vitamin D levels and weight loss via caloric restriction and exercise showed a small but significant effect in the sense that weight loss increases vitamin D levels. However, other meta-analyses have not found significant results in this area,” she said.

“In my opinion, these results depend on how long the intervention is performed. If a lot of weight is lost in a short time frame, vitamin D is released into the adipose tissue, a process that doesn’t have any significant impact on the nutritional status of this vitamin. Generally, the effect of this relationship is small (1.5 ng/mL) and of little clinical relevance. Moreover, many systematic reviews have analyzed this relationship following bariatric surgery and have also come up with inconclusive results,” Dr. Bretón added.

What role do treatments play in correcting vitamin D deficiency? Dr. Bretón explained that studies that have examined how fortified foods affect obesity show that though these foods don’t cause significant weight changes, they do affect fat mass and waist circumference. This finding suggests that fortified foods have some impact, not necessarily on weight but perhaps on adiposity.

“To rightly value all this data, one has to pay special attention to the environment and the context where the research took place (children or adults, baseline vitamin D levels, and so on). If fortified foods are directly supplemented with cholecalciferol, the results are very inconsistent. We therefore cannot say that treatment with vitamin D can reduce body weight and adiposity,” she said.

When it comes to the complications from obesity, studies of vitamin D supplementation, cancer, and cardiovascular disease did not find any beneficial effect on preventing these pathologies.

For obesity’s impact on vitamin D supplementation, it is known that the levels achieved are lower in patients with obesity compared with patients of normal weight. “Compared with other interventions, however, these levels (15.27 ng/mL) are clinically relevant,” she noted.
 

Future Directions

Dr. Bretón explained that all this evidence has revealed many debates regarding the association of vitamin D levels with obesity. “For example, it appears that obesity could predict low vitamin D levels (not necessarily a deficiency). In turn, these low levels could cause obesity, especially during embryonic development, when programming of adipocyte physiology is taking place.”

Dr. Bretón sees many confounding factors that will need to be elucidated in the future. “One factor is that we aren’t sure whether the patient we’re seeing has vitamin D deficiency or if other factors are in play, like time since weight loss, laboratory technique used to measure vitamin D, nutritional status, geographic location, time of year when the test is performed, et cetera. You also have to assess other factors having to do with obesity, like how adiposity is being measured and whether BMI reflects that adiposity.”

Last, the expert reviewed the major research efforts underway that are based on evidence that vitamin D is associated with insulin resistance. Studies are being performed on pancreatic function, the role of vitamin D levels in ovarian physiology related to insulin resistance (specifically, the role of hyperandrogenism), adipose tissue (vitamin D receptor expression, volumetric dilution), and other components of metabolic syndrome to determine how this vitamin’s status influences the renin-angiotensin system, apoptosis, and cardiovascular risk.

“There is also plenty of research going on surrounding metabolic liver disease, which has a lot to do with the microbiota. So, they’re studying the relationship between vitamin D and dysbiosis, especially regarding local immunomodulation in the gut in relation to the microbiota,” she added.

Another area of research is cancer, focusing primarily on analyzing the nutritional status of vitamin D in relation to the microbiome and how this status may affect the therapeutic effect of chemotherapy and radiation therapy. “It would be interesting to find out whether the effect of immunotherapy varies depending on the patient’s vitamin D status,” concluded Dr. Bretón.

Dr. Bretón’s lecture at the 64th Congress of the SEEN was sponsored by the Foundation for Analysis and Social Studies (FAES).

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

MADRID — The role of vitamin D in the risk for overweight and obesity has been the subject of multiple studies. Though there’s still not enough evidence to reach a decisive conclusion, several ongoing debates are setting the stage for future research.

Irene Bretón, MD, PhD, discussed these debates in a presentation titled “Vitamin D Deficiency and Obesity: Cause or Consequence?” delivered at the 64th Congress of the Spanish Society of Endocrinology and Nutrition (SEEN). Dr. Bretón is president of the Foundation of the Spanish Society of Endocrinology and Nutrition.

“Vitamin D deficiency can arise from different causes. The percentage that can be attributed to solar radiation is extremely variable. Some studies put it at 80%, while others suggest lower figures. Many diseases have also been associated with vitamin D deficiency or with low vitamin D levels (which are not always at the level of deficiency). Nonetheless, we still have a lot to learn about these associations,” she said.

Dr. Bretón pointed out that many of these studies overlook parathyroid hormone testing. “I also think it’s more appropriate to discuss nutritional status of vitamin D as opposed to serum levels, because these data can be misleading. It would be interesting to focus more on vitamin D metabolism and not just plasma levels.”
 

Vitamin Deficiency 

To answer whether obesity and its complications could be related to low vitamin D levels, Dr. Bretón pointed to this vitamin’s profile in various regions of the world and called attention to the fact that none of the studies on this topic include populations with roughly adequate levels of this vitamin.

“This highlights the prevalence of vitamin D deficiency worldwide. It affects approximately 50% of the population, has been described in all age groups, and affects both men and women — particularly pregnant women and those in menopause — and older adults,” said Dr. Bretón.

She also cited the figures backing this fact: 88% have 25-hydroxyvitamin D levels < 30 ng/mL, 37% have levels < 20 ng/mL, and 7% have levels < 10 ng/mL.

“These percentages have brought us to consider their potential link to the current obesity epidemic. Studies in humans have observed a relationship between low plasma levels and markers for obesity and adiposity. Free 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D are known to be reduced in obesity, and treatments to correct vitamin D deficiency are less effective in people with the disease,” she noted.

Regarding the impact in “the opposite direction,” that is, whether obesity affects the nutritional status of vitamin D, Bretón explained that observational studies have generally found a relationship between overweight and obesity and lower plasma levels of vitamin D. “Data from these studies show that each kg/m² increase in [body mass index (BMI)] is associated with a 1.15% decrease in 25-hydroxyvitamin D. These studies also show that the prevalence of vitamin D deficiency is 35% higher in patients with obesity and 24% higher in those that are overweight compared with individuals of normal weight. A relationship has been observed between vitamin D deficiency and body fat percentage in men and women and in all age groups,” explained Dr. Bretón.

Dr. Bretón noted that the diseases most closely associated with obesity are type 2 diabetes, hypertension, ischemic heart disease, cancer (colon, breast, prostate, and ovarian), inflammatory liver disease, asthma, and inflammatory diseases.
 

Mechanisms Involved

Dr. Bretón reviewed the latest evidence on the mechanisms involved in the relationship between obesity and vitamin D deficiency. “People with obesity may experience less solar exposure (more of their body is covered, or they spend more time indoors), but reduced exposure to the sun is known to have less of an influence on vitamin D levels. Studies where people were given radiation to test how their plasma levels of vitamin D respond have found that there is a smaller effect in people with obesity, and that the effect is inversely correlated with BMI: the higher the BMI, the less vitamin D levels increase under exposure to solar radiation.”

Another mechanism is sequestration in adipose tissue, which is the largest reservoir of vitamin D in the body. Nevertheless, factors such as vitamin D concentration in this tissue, regulation of local metabolism, and vitamin uptake and release are less understood. It is therefore unclear whether this mechanism acts to regulate plasma levels.

“This is why severe vitamin D deficiencies (and deficiencies of other fat-soluble vitamins) that occur after bariatric surgery are often not seen in the first year after surgery but develop much later, when the vitamin that has accumulated in adipose tissue is released as weight is lost,” said Dr. Bretón.

“On the other hand, the volumetric dilution in blood that occurs in relation to total body fat content may explain the variability of plasma levels and the response to treatment. Predictive equations have been described,” she explained.
 

The Prenatal Stage

Dr. Bretón mentioned that the best setting for studying the impact of vitamin D and preventing future obesity is during the initial stages of life, when adipogenesis and fetal programming are occurring.

“Studies in animals have shown how maternal vitamin D deficiency (due to nongenetic or nonepigenetic mechanisms) leads to changes in adipogenesis and programming of adipose reserves. A fetal or perinatal environment with low vitamin D levels programs all these mechanisms differently, and not just adipogenesis and adipocyte differentiation in utero,” she added.

Various mechanisms involved in vitamin D deficiency as a cause of obesity are currently being studied in the prenatal setting. One such mechanism is the interaction between the vitamin D receptor and 1 alpha–hydroxylase, which are present in the adipose tissue and help modulate lipid metabolism.

“The vitamin D receptor is particularly expressed in the early stages of adipocyte differentiation, but its expression drops off as the differentiation process continues. Vitamin D receptor knockout mice have a slender phenotype and are resistant to diet-induced obesity. They also accumulate less fat with age and a high-fat diet,” explained Dr. Bretón.

“However, vitamin D also influences the production of inflammatory adipokines in these early stages of life. It specifically plays a central role in modulating the inflammatory response in adipose tissue. These anti-inflammatory effects appear to be mediated by inhibition of [NF–kappa B] and MAPK signaling pathways. All of this suggests that vitamin D influences both adipogenesis and how the adipose tissue functions,” she added.
 

Weight Loss 

When considering the link between vitamin D and obesity in the context of weight loss, Dr. Bretón explained that studies in this area suggest that weight loss per se is not sufficient to increase serum 25-hydroxyvitamin D. Rather, increased synthesis by the skin or increased dietary intake are the most relevant factors for the nutritional status of this vitamin.

“A recent systematic review looking at the relationship between vitamin D levels and weight loss via caloric restriction and exercise showed a small but significant effect in the sense that weight loss increases vitamin D levels. However, other meta-analyses have not found significant results in this area,” she said.

“In my opinion, these results depend on how long the intervention is performed. If a lot of weight is lost in a short time frame, vitamin D is released into the adipose tissue, a process that doesn’t have any significant impact on the nutritional status of this vitamin. Generally, the effect of this relationship is small (1.5 ng/mL) and of little clinical relevance. Moreover, many systematic reviews have analyzed this relationship following bariatric surgery and have also come up with inconclusive results,” Dr. Bretón added.

What role do treatments play in correcting vitamin D deficiency? Dr. Bretón explained that studies that have examined how fortified foods affect obesity show that though these foods don’t cause significant weight changes, they do affect fat mass and waist circumference. This finding suggests that fortified foods have some impact, not necessarily on weight but perhaps on adiposity.

“To rightly value all this data, one has to pay special attention to the environment and the context where the research took place (children or adults, baseline vitamin D levels, and so on). If fortified foods are directly supplemented with cholecalciferol, the results are very inconsistent. We therefore cannot say that treatment with vitamin D can reduce body weight and adiposity,” she said.

When it comes to the complications from obesity, studies of vitamin D supplementation, cancer, and cardiovascular disease did not find any beneficial effect on preventing these pathologies.

For obesity’s impact on vitamin D supplementation, it is known that the levels achieved are lower in patients with obesity compared with patients of normal weight. “Compared with other interventions, however, these levels (15.27 ng/mL) are clinically relevant,” she noted.
 

Future Directions

Dr. Bretón explained that all this evidence has revealed many debates regarding the association of vitamin D levels with obesity. “For example, it appears that obesity could predict low vitamin D levels (not necessarily a deficiency). In turn, these low levels could cause obesity, especially during embryonic development, when programming of adipocyte physiology is taking place.”

Dr. Bretón sees many confounding factors that will need to be elucidated in the future. “One factor is that we aren’t sure whether the patient we’re seeing has vitamin D deficiency or if other factors are in play, like time since weight loss, laboratory technique used to measure vitamin D, nutritional status, geographic location, time of year when the test is performed, et cetera. You also have to assess other factors having to do with obesity, like how adiposity is being measured and whether BMI reflects that adiposity.”

Last, the expert reviewed the major research efforts underway that are based on evidence that vitamin D is associated with insulin resistance. Studies are being performed on pancreatic function, the role of vitamin D levels in ovarian physiology related to insulin resistance (specifically, the role of hyperandrogenism), adipose tissue (vitamin D receptor expression, volumetric dilution), and other components of metabolic syndrome to determine how this vitamin’s status influences the renin-angiotensin system, apoptosis, and cardiovascular risk.

“There is also plenty of research going on surrounding metabolic liver disease, which has a lot to do with the microbiota. So, they’re studying the relationship between vitamin D and dysbiosis, especially regarding local immunomodulation in the gut in relation to the microbiota,” she added.

Another area of research is cancer, focusing primarily on analyzing the nutritional status of vitamin D in relation to the microbiome and how this status may affect the therapeutic effect of chemotherapy and radiation therapy. “It would be interesting to find out whether the effect of immunotherapy varies depending on the patient’s vitamin D status,” concluded Dr. Bretón.

Dr. Bretón’s lecture at the 64th Congress of the SEEN was sponsored by the Foundation for Analysis and Social Studies (FAES).

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

MADRID — The role of vitamin D in the risk for overweight and obesity has been the subject of multiple studies. Though there’s still not enough evidence to reach a decisive conclusion, several ongoing debates are setting the stage for future research.

Irene Bretón, MD, PhD, discussed these debates in a presentation titled “Vitamin D Deficiency and Obesity: Cause or Consequence?” delivered at the 64th Congress of the Spanish Society of Endocrinology and Nutrition (SEEN). Dr. Bretón is president of the Foundation of the Spanish Society of Endocrinology and Nutrition.

“Vitamin D deficiency can arise from different causes. The percentage that can be attributed to solar radiation is extremely variable. Some studies put it at 80%, while others suggest lower figures. Many diseases have also been associated with vitamin D deficiency or with low vitamin D levels (which are not always at the level of deficiency). Nonetheless, we still have a lot to learn about these associations,” she said.

Dr. Bretón pointed out that many of these studies overlook parathyroid hormone testing. “I also think it’s more appropriate to discuss nutritional status of vitamin D as opposed to serum levels, because these data can be misleading. It would be interesting to focus more on vitamin D metabolism and not just plasma levels.”
 

Vitamin Deficiency 

To answer whether obesity and its complications could be related to low vitamin D levels, Dr. Bretón pointed to this vitamin’s profile in various regions of the world and called attention to the fact that none of the studies on this topic include populations with roughly adequate levels of this vitamin.

“This highlights the prevalence of vitamin D deficiency worldwide. It affects approximately 50% of the population, has been described in all age groups, and affects both men and women — particularly pregnant women and those in menopause — and older adults,” said Dr. Bretón.

She also cited the figures backing this fact: 88% have 25-hydroxyvitamin D levels < 30 ng/mL, 37% have levels < 20 ng/mL, and 7% have levels < 10 ng/mL.

“These percentages have brought us to consider their potential link to the current obesity epidemic. Studies in humans have observed a relationship between low plasma levels and markers for obesity and adiposity. Free 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D are known to be reduced in obesity, and treatments to correct vitamin D deficiency are less effective in people with the disease,” she noted.

Regarding the impact in “the opposite direction,” that is, whether obesity affects the nutritional status of vitamin D, Bretón explained that observational studies have generally found a relationship between overweight and obesity and lower plasma levels of vitamin D. “Data from these studies show that each kg/m² increase in [body mass index (BMI)] is associated with a 1.15% decrease in 25-hydroxyvitamin D. These studies also show that the prevalence of vitamin D deficiency is 35% higher in patients with obesity and 24% higher in those that are overweight compared with individuals of normal weight. A relationship has been observed between vitamin D deficiency and body fat percentage in men and women and in all age groups,” explained Dr. Bretón.

Dr. Bretón noted that the diseases most closely associated with obesity are type 2 diabetes, hypertension, ischemic heart disease, cancer (colon, breast, prostate, and ovarian), inflammatory liver disease, asthma, and inflammatory diseases.
 

Mechanisms Involved

Dr. Bretón reviewed the latest evidence on the mechanisms involved in the relationship between obesity and vitamin D deficiency. “People with obesity may experience less solar exposure (more of their body is covered, or they spend more time indoors), but reduced exposure to the sun is known to have less of an influence on vitamin D levels. Studies where people were given radiation to test how their plasma levels of vitamin D respond have found that there is a smaller effect in people with obesity, and that the effect is inversely correlated with BMI: the higher the BMI, the less vitamin D levels increase under exposure to solar radiation.”

Another mechanism is sequestration in adipose tissue, which is the largest reservoir of vitamin D in the body. Nevertheless, factors such as vitamin D concentration in this tissue, regulation of local metabolism, and vitamin uptake and release are less understood. It is therefore unclear whether this mechanism acts to regulate plasma levels.

“This is why severe vitamin D deficiencies (and deficiencies of other fat-soluble vitamins) that occur after bariatric surgery are often not seen in the first year after surgery but develop much later, when the vitamin that has accumulated in adipose tissue is released as weight is lost,” said Dr. Bretón.

“On the other hand, the volumetric dilution in blood that occurs in relation to total body fat content may explain the variability of plasma levels and the response to treatment. Predictive equations have been described,” she explained.
 

The Prenatal Stage

Dr. Bretón mentioned that the best setting for studying the impact of vitamin D and preventing future obesity is during the initial stages of life, when adipogenesis and fetal programming are occurring.

“Studies in animals have shown how maternal vitamin D deficiency (due to nongenetic or nonepigenetic mechanisms) leads to changes in adipogenesis and programming of adipose reserves. A fetal or perinatal environment with low vitamin D levels programs all these mechanisms differently, and not just adipogenesis and adipocyte differentiation in utero,” she added.

Various mechanisms involved in vitamin D deficiency as a cause of obesity are currently being studied in the prenatal setting. One such mechanism is the interaction between the vitamin D receptor and 1 alpha–hydroxylase, which are present in the adipose tissue and help modulate lipid metabolism.

“The vitamin D receptor is particularly expressed in the early stages of adipocyte differentiation, but its expression drops off as the differentiation process continues. Vitamin D receptor knockout mice have a slender phenotype and are resistant to diet-induced obesity. They also accumulate less fat with age and a high-fat diet,” explained Dr. Bretón.

“However, vitamin D also influences the production of inflammatory adipokines in these early stages of life. It specifically plays a central role in modulating the inflammatory response in adipose tissue. These anti-inflammatory effects appear to be mediated by inhibition of [NF–kappa B] and MAPK signaling pathways. All of this suggests that vitamin D influences both adipogenesis and how the adipose tissue functions,” she added.
 

Weight Loss 

When considering the link between vitamin D and obesity in the context of weight loss, Dr. Bretón explained that studies in this area suggest that weight loss per se is not sufficient to increase serum 25-hydroxyvitamin D. Rather, increased synthesis by the skin or increased dietary intake are the most relevant factors for the nutritional status of this vitamin.

“A recent systematic review looking at the relationship between vitamin D levels and weight loss via caloric restriction and exercise showed a small but significant effect in the sense that weight loss increases vitamin D levels. However, other meta-analyses have not found significant results in this area,” she said.

“In my opinion, these results depend on how long the intervention is performed. If a lot of weight is lost in a short time frame, vitamin D is released into the adipose tissue, a process that doesn’t have any significant impact on the nutritional status of this vitamin. Generally, the effect of this relationship is small (1.5 ng/mL) and of little clinical relevance. Moreover, many systematic reviews have analyzed this relationship following bariatric surgery and have also come up with inconclusive results,” Dr. Bretón added.

What role do treatments play in correcting vitamin D deficiency? Dr. Bretón explained that studies that have examined how fortified foods affect obesity show that though these foods don’t cause significant weight changes, they do affect fat mass and waist circumference. This finding suggests that fortified foods have some impact, not necessarily on weight but perhaps on adiposity.

“To rightly value all this data, one has to pay special attention to the environment and the context where the research took place (children or adults, baseline vitamin D levels, and so on). If fortified foods are directly supplemented with cholecalciferol, the results are very inconsistent. We therefore cannot say that treatment with vitamin D can reduce body weight and adiposity,” she said.

When it comes to the complications from obesity, studies of vitamin D supplementation, cancer, and cardiovascular disease did not find any beneficial effect on preventing these pathologies.

For obesity’s impact on vitamin D supplementation, it is known that the levels achieved are lower in patients with obesity compared with patients of normal weight. “Compared with other interventions, however, these levels (15.27 ng/mL) are clinically relevant,” she noted.
 

Future Directions

Dr. Bretón explained that all this evidence has revealed many debates regarding the association of vitamin D levels with obesity. “For example, it appears that obesity could predict low vitamin D levels (not necessarily a deficiency). In turn, these low levels could cause obesity, especially during embryonic development, when programming of adipocyte physiology is taking place.”

Dr. Bretón sees many confounding factors that will need to be elucidated in the future. “One factor is that we aren’t sure whether the patient we’re seeing has vitamin D deficiency or if other factors are in play, like time since weight loss, laboratory technique used to measure vitamin D, nutritional status, geographic location, time of year when the test is performed, et cetera. You also have to assess other factors having to do with obesity, like how adiposity is being measured and whether BMI reflects that adiposity.”

Last, the expert reviewed the major research efforts underway that are based on evidence that vitamin D is associated with insulin resistance. Studies are being performed on pancreatic function, the role of vitamin D levels in ovarian physiology related to insulin resistance (specifically, the role of hyperandrogenism), adipose tissue (vitamin D receptor expression, volumetric dilution), and other components of metabolic syndrome to determine how this vitamin’s status influences the renin-angiotensin system, apoptosis, and cardiovascular risk.

“There is also plenty of research going on surrounding metabolic liver disease, which has a lot to do with the microbiota. So, they’re studying the relationship between vitamin D and dysbiosis, especially regarding local immunomodulation in the gut in relation to the microbiota,” she added.

Another area of research is cancer, focusing primarily on analyzing the nutritional status of vitamin D in relation to the microbiome and how this status may affect the therapeutic effect of chemotherapy and radiation therapy. “It would be interesting to find out whether the effect of immunotherapy varies depending on the patient’s vitamin D status,” concluded Dr. Bretón.

Dr. Bretón’s lecture at the 64th Congress of the SEEN was sponsored by the Foundation for Analysis and Social Studies (FAES).

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

Patients receiving semaglutide for weight loss show a significantly higher rate of continuing the medication at 1 year compared with less effective anti-obesity drugs. However, even among those patients, continuation declines to fewer than half of patients.

“We now have effective US Food and Drug Administration–approved anti-obesity medications; [however], this study shows that in a real-world setting, the vast majority of patients discontinued their prescription fills within the first year,” said first author Hamlet Gasoyan, PhD, lead author of the study and a researcher with Cleveland Clinic’s Center for Value-Based Care Research, said in a press statement.

The study was published online in the journal Obesity.

While breakthrough drugs such as glucagon-like peptide-1 (GLP-1) receptor agonists have shown high efficacy in achieving weight loss while providing a host of other health benefits, their discontinuation has been shown to potentially result in a rapid regaining of weight that was lost, as well as a reversal of the other health benefits, such as cardiometabolic improvements, the study authors wrote.

To evaluate rates of persistence with those along with other weight loss medications and factors associated with discontinuation, Dr. Gasoyan and colleagues conducted a retrospective cohort study, identifying 1911 patients with obesity, who had an initial anti-obesity medication prescription filled between 2015 and 2022 at Cleveland Clinic centers in Ohio and Florida. 

Over the study period, 25% of patients filled a prescription for semaglutide, 34% for naltrexone-bupropion, 26% for phentermine-topiramate, 14% for liraglutide, and 0.9% for orlistat.

The patients had a median baseline BMI of 38, with obesity defined as a BMI of 30 or higher.
 

Medication Continuation Drops After 3 Months

With a median follow-up time of 2.4 years, the rate of persistence to the medications overall dropped from 44% at 3 months to 33% at 6 months and just 19% at 12 months. 

In a multivariate analysis, semaglutide was associated with the highest odds of 1-year persistence (adjusted odds ratio [AOR], 4.26), while naltrexone-bupropion had the lowest odds (AOR, 0.68), compared with phentermine-topiramate. The other agents did not have significantly different odds of persistence.

Semaglutide and liraglutide also had the highest persistence rates overall, including at 3 months (63% and 52%, respectively) and 6 months (56% and 37%, respectively).

Those with higher weight loss at 6 months had a higher likelihood of remaining on the weight loss medication at 1 year, with a 1% increase in weight loss at 6 months associated with 6% increased odds of still being persistent at year 1 (adjusted odds ratio, 1.06).

Those who did continue medications at 1 year had a mean of 10% weight loss at 12 months compared with just 2% among individuals who were not persistent (P <.001).

Most patients (84%) in the study were privately insured, and weight loss drug adherence varied significantly based on the insurance carrier. 

Studies demonstrating the effects of discontinuing treatment with semaglutide include the STEP 1 trial extension, which showed that 1 year after discontinuation of treatment and lifestyle intervention, participants regained two thirds of their lost weight on average, and the cardiometabolic improvements with the weight loss were reversed.

In light of those findings, “the current scientific knowledge favors using anti-obesity medications longer term for weight loss maintenance if they are well-tolerated and have resulted in clinically meaningful weight loss,” Dr. Gasoyan told this news organization. 

Paradoxically, the possible regaining of weight could be a factor in some insurers denying longer-term coverage, he noted.
 

Discontinuing Medications Means Regaining Appetite

Anne Peters, MD, a professor of medicine at USC’s Keck School of Medicine in Los Angeles and director of the USC Clinical Diabetes Programs, underscored that the possibility of regaining weight with discontinuation of GLP-1 receptor agonists is indeed “a big concern because your appetite comes back in spades when you take away the effect of these hormones,” she told this news organization. “For that reason, I don’t ever tell people to stop cold turkey.”

Regarding the question of how long patients should remain on the medications, Peters said the scenario might be compared to the need for patients with type 1 diabetes to be on insulin, which is a gut hormone.

“These medications are also gut hormones, and some patients may need to also be on them for life to maintain the benefits,” she said. 

“If a patient for some reason wishes to come off of the medication, for instance in order to be on less medicine, I have them titrate down and usually there will be a dose where they actually need only a small dose.

“I even have some patients who just take semaglutide once a month who are able to manage to maintain their weight loss,” Dr. Peters noted. 

“But the whole goal in people who are overweight or obese is to establish a new set point and maintain whatever that new target weight is.”

Dr. Peters agreed that the loss of insurance coverage for the medications can throw a big wrench into that maintenance, presenting adverse effects of its own by causing a lack of treatment continuity. 

“When you lose weight, you lose lean body mass and fat mass, but when you regain, it’s primary fat mass, so if you go on and off these drugs, it can contribute to a loss of lean mass. Therefore, these drugs should not be taken if someone is going to go on and off them repeatedly.” 

The study received funding from the National Cancer Institute. Dr. Peters has consulted for Eli Lilly in the past.

A version of this article appeared on Medscape.com.

Patients receiving semaglutide for weight loss show a significantly higher rate of continuing the medication at 1 year compared with less effective anti-obesity drugs. However, even among those patients, continuation declines to fewer than half of patients.

“We now have effective US Food and Drug Administration–approved anti-obesity medications; [however], this study shows that in a real-world setting, the vast majority of patients discontinued their prescription fills within the first year,” said first author Hamlet Gasoyan, PhD, lead author of the study and a researcher with Cleveland Clinic’s Center for Value-Based Care Research, said in a press statement.

The study was published online in the journal Obesity.

While breakthrough drugs such as glucagon-like peptide-1 (GLP-1) receptor agonists have shown high efficacy in achieving weight loss while providing a host of other health benefits, their discontinuation has been shown to potentially result in a rapid regaining of weight that was lost, as well as a reversal of the other health benefits, such as cardiometabolic improvements, the study authors wrote.

To evaluate rates of persistence with those along with other weight loss medications and factors associated with discontinuation, Dr. Gasoyan and colleagues conducted a retrospective cohort study, identifying 1911 patients with obesity, who had an initial anti-obesity medication prescription filled between 2015 and 2022 at Cleveland Clinic centers in Ohio and Florida. 

Over the study period, 25% of patients filled a prescription for semaglutide, 34% for naltrexone-bupropion, 26% for phentermine-topiramate, 14% for liraglutide, and 0.9% for orlistat.

The patients had a median baseline BMI of 38, with obesity defined as a BMI of 30 or higher.
 

Medication Continuation Drops After 3 Months

With a median follow-up time of 2.4 years, the rate of persistence to the medications overall dropped from 44% at 3 months to 33% at 6 months and just 19% at 12 months. 

In a multivariate analysis, semaglutide was associated with the highest odds of 1-year persistence (adjusted odds ratio [AOR], 4.26), while naltrexone-bupropion had the lowest odds (AOR, 0.68), compared with phentermine-topiramate. The other agents did not have significantly different odds of persistence.

Semaglutide and liraglutide also had the highest persistence rates overall, including at 3 months (63% and 52%, respectively) and 6 months (56% and 37%, respectively).

Those with higher weight loss at 6 months had a higher likelihood of remaining on the weight loss medication at 1 year, with a 1% increase in weight loss at 6 months associated with 6% increased odds of still being persistent at year 1 (adjusted odds ratio, 1.06).

Those who did continue medications at 1 year had a mean of 10% weight loss at 12 months compared with just 2% among individuals who were not persistent (P <.001).

Most patients (84%) in the study were privately insured, and weight loss drug adherence varied significantly based on the insurance carrier. 

Studies demonstrating the effects of discontinuing treatment with semaglutide include the STEP 1 trial extension, which showed that 1 year after discontinuation of treatment and lifestyle intervention, participants regained two thirds of their lost weight on average, and the cardiometabolic improvements with the weight loss were reversed.

In light of those findings, “the current scientific knowledge favors using anti-obesity medications longer term for weight loss maintenance if they are well-tolerated and have resulted in clinically meaningful weight loss,” Dr. Gasoyan told this news organization. 

Paradoxically, the possible regaining of weight could be a factor in some insurers denying longer-term coverage, he noted.
 

Discontinuing Medications Means Regaining Appetite

Anne Peters, MD, a professor of medicine at USC’s Keck School of Medicine in Los Angeles and director of the USC Clinical Diabetes Programs, underscored that the possibility of regaining weight with discontinuation of GLP-1 receptor agonists is indeed “a big concern because your appetite comes back in spades when you take away the effect of these hormones,” she told this news organization. “For that reason, I don’t ever tell people to stop cold turkey.”

Regarding the question of how long patients should remain on the medications, Peters said the scenario might be compared to the need for patients with type 1 diabetes to be on insulin, which is a gut hormone.

“These medications are also gut hormones, and some patients may need to also be on them for life to maintain the benefits,” she said. 

“If a patient for some reason wishes to come off of the medication, for instance in order to be on less medicine, I have them titrate down and usually there will be a dose where they actually need only a small dose.

“I even have some patients who just take semaglutide once a month who are able to manage to maintain their weight loss,” Dr. Peters noted. 

“But the whole goal in people who are overweight or obese is to establish a new set point and maintain whatever that new target weight is.”

Dr. Peters agreed that the loss of insurance coverage for the medications can throw a big wrench into that maintenance, presenting adverse effects of its own by causing a lack of treatment continuity. 

“When you lose weight, you lose lean body mass and fat mass, but when you regain, it’s primary fat mass, so if you go on and off these drugs, it can contribute to a loss of lean mass. Therefore, these drugs should not be taken if someone is going to go on and off them repeatedly.” 

The study received funding from the National Cancer Institute. Dr. Peters has consulted for Eli Lilly in the past.

A version of this article appeared on Medscape.com.

Patients receiving semaglutide for weight loss show a significantly higher rate of continuing the medication at 1 year compared with less effective anti-obesity drugs. However, even among those patients, continuation declines to fewer than half of patients.

“We now have effective US Food and Drug Administration–approved anti-obesity medications; [however], this study shows that in a real-world setting, the vast majority of patients discontinued their prescription fills within the first year,” said first author Hamlet Gasoyan, PhD, lead author of the study and a researcher with Cleveland Clinic’s Center for Value-Based Care Research, said in a press statement.

The study was published online in the journal Obesity.

While breakthrough drugs such as glucagon-like peptide-1 (GLP-1) receptor agonists have shown high efficacy in achieving weight loss while providing a host of other health benefits, their discontinuation has been shown to potentially result in a rapid regaining of weight that was lost, as well as a reversal of the other health benefits, such as cardiometabolic improvements, the study authors wrote.

To evaluate rates of persistence with those along with other weight loss medications and factors associated with discontinuation, Dr. Gasoyan and colleagues conducted a retrospective cohort study, identifying 1911 patients with obesity, who had an initial anti-obesity medication prescription filled between 2015 and 2022 at Cleveland Clinic centers in Ohio and Florida. 

Over the study period, 25% of patients filled a prescription for semaglutide, 34% for naltrexone-bupropion, 26% for phentermine-topiramate, 14% for liraglutide, and 0.9% for orlistat.

The patients had a median baseline BMI of 38, with obesity defined as a BMI of 30 or higher.
 

Medication Continuation Drops After 3 Months

With a median follow-up time of 2.4 years, the rate of persistence to the medications overall dropped from 44% at 3 months to 33% at 6 months and just 19% at 12 months. 

In a multivariate analysis, semaglutide was associated with the highest odds of 1-year persistence (adjusted odds ratio [AOR], 4.26), while naltrexone-bupropion had the lowest odds (AOR, 0.68), compared with phentermine-topiramate. The other agents did not have significantly different odds of persistence.

Semaglutide and liraglutide also had the highest persistence rates overall, including at 3 months (63% and 52%, respectively) and 6 months (56% and 37%, respectively).

Those with higher weight loss at 6 months had a higher likelihood of remaining on the weight loss medication at 1 year, with a 1% increase in weight loss at 6 months associated with 6% increased odds of still being persistent at year 1 (adjusted odds ratio, 1.06).

Those who did continue medications at 1 year had a mean of 10% weight loss at 12 months compared with just 2% among individuals who were not persistent (P <.001).

Most patients (84%) in the study were privately insured, and weight loss drug adherence varied significantly based on the insurance carrier. 

Studies demonstrating the effects of discontinuing treatment with semaglutide include the STEP 1 trial extension, which showed that 1 year after discontinuation of treatment and lifestyle intervention, participants regained two thirds of their lost weight on average, and the cardiometabolic improvements with the weight loss were reversed.

In light of those findings, “the current scientific knowledge favors using anti-obesity medications longer term for weight loss maintenance if they are well-tolerated and have resulted in clinically meaningful weight loss,” Dr. Gasoyan told this news organization. 

Paradoxically, the possible regaining of weight could be a factor in some insurers denying longer-term coverage, he noted.
 

Discontinuing Medications Means Regaining Appetite

Anne Peters, MD, a professor of medicine at USC’s Keck School of Medicine in Los Angeles and director of the USC Clinical Diabetes Programs, underscored that the possibility of regaining weight with discontinuation of GLP-1 receptor agonists is indeed “a big concern because your appetite comes back in spades when you take away the effect of these hormones,” she told this news organization. “For that reason, I don’t ever tell people to stop cold turkey.”

Regarding the question of how long patients should remain on the medications, Peters said the scenario might be compared to the need for patients with type 1 diabetes to be on insulin, which is a gut hormone.

“These medications are also gut hormones, and some patients may need to also be on them for life to maintain the benefits,” she said. 

“If a patient for some reason wishes to come off of the medication, for instance in order to be on less medicine, I have them titrate down and usually there will be a dose where they actually need only a small dose.

“I even have some patients who just take semaglutide once a month who are able to manage to maintain their weight loss,” Dr. Peters noted. 

“But the whole goal in people who are overweight or obese is to establish a new set point and maintain whatever that new target weight is.”

Dr. Peters agreed that the loss of insurance coverage for the medications can throw a big wrench into that maintenance, presenting adverse effects of its own by causing a lack of treatment continuity. 

“When you lose weight, you lose lean body mass and fat mass, but when you regain, it’s primary fat mass, so if you go on and off these drugs, it can contribute to a loss of lean mass. Therefore, these drugs should not be taken if someone is going to go on and off them repeatedly.” 

The study received funding from the National Cancer Institute. Dr. Peters has consulted for Eli Lilly in the past.

A version of this article appeared on Medscape.com.

Primary care clinicians play a central role in maintaining the cardiovascular-kidney-metabolic (CKM) health of patients, according to a new advisory from the American Heart Association.

The advisory, published recently in Circulation introduces the concept of CKM health and reevaluates the relationships between obesity, diabetes, kidney disease, and cardiovascular disease (CVD).

“This approach not only raises awareness, it also empowers PCPs to diagnose and treat these conditions more holistically,” Salim Hayek, MD, associate professor of cardiovascular disease and internal medicine, and medical director of the Frankel Cardiovascular Center Clinics at the University of Michigan in Ann Arbor, said in an interview.

 

New CKM Staging, Testing, and Care Strategies

The advisory introduces a new scoring system that ranges from stage 0 (patients with no risk factors for CKM) through stage 4 (patients with clinical CVD in CKM syndrome). Each stage requires specific management strategies and may include screening starting at age 30 years for diabetes, hypertension, and heart failure.

“Stage 0 CKM is usually found in young people, and CKM risk factors and scores typically increase as people age,” said Sean M. Drake, MD, a primary care physician at Henry Ford Health in Sterling Heights, Michigan. 

Dr. Drake advised PCPs to encourage patients who are at stage 0 to maintain ideal cardiovascular health and to monitor those at risk of progressing through the stages.

While PCPs already perform many of the tests the advisory recommends, the conditions overlap and an abnormality in one system should prompt more testing for other conditions. Additional tests, such as urine albumin-creatinine ratio, and more frequent glomerular filtration rate and lipid profile are advised, according to Dr. Drake.

“There also appears to be a role for additional cardiac testing, including echocardiograms and coronary CT scans, and for liver fibrosis screening,” Dr. Drake said. “Medications such as SGLT2 inhibitors, GLP-1 receptor agonists, and ACE inhibitors, beyond current routine use, are emphasized.” 

To better characterize body composition and help diagnose metabolic syndrome, the advisory also recommends measuring waist circumference, which is not routine practice, noted Joshua J. Joseph, MD, MPH, an associate professor of endocrinology, diabetes, and metabolism at The Ohio State University Wexner Medical Center in Columbus, and a co-author of the advisory. 

Recognizing the interconnected nature of cardiac, kidney, and metabolic diseases encourages a shift in mindset for clinicians, according to Neha Pagidipati, MD, MPH, a cardiologist at Duke Health in Durham, North Carolina.

“We have often been trained to focus on the specific problem in front of us,” Dr. Pagidipati said. “We need to be hyper-aware that many patients we see are at risk for multiple CKM entities. We need to be proactive about screening for and treating these when appropriate.”

The advisory emphasizes the need for CKM coordinators to support teams of clinicians from primary care, cardiology, endocrinology, nephrology, nursing, and pharmacy, as well as social workers, care navigators, or community health workers, Dr. Joseph said. 

“The advisory repositions the PCP at the forefront of CKM care coordination, marking a departure from the traditional model where subspecialists primarily manage complications,” Dr. Hayek added.
 

Changes to Payment

The new recommendations are consistent with current management guidelines for obesity, hypertriglyceridemia, hypertension, type 2 diabetes, and chronic kidney disease. 

“The advisory provides integrated algorithms for cardiovascular prevention and management, with specific therapeutic guidance tied to CKM stages, bringing together the current evidence for best practices from the various guidelines and filling gaps in a unified approach,” Dr. Joseph said. 

In addition, the advisory draws attention to the care of younger patients, who may be at increased risk for cardiovascular disease due to lifestyle factors, according to Nishant Shah, MD, assistant professor of medicine at Duke. 

“It considers barriers to care that prevent people from optimizing their cardiovascular health,” Dr. Shah said. 

Although the advisory does not specify proposed payment changes to support the new care model, the move towards value-based care may require billing practices that accommodate integrated care as well as more frequent and more specialized testing, Dr. Hayek said. 

“The advisory is an empowering tool for PCPs, underscoring their critical role in healthcare,” Dr. Hayek said. “It encourages PCPs to advocate for integrated care within their practices and to consider workflow adjustments that enhance the identification and initiation of preventive care for at-risk patients.”

Funding information was not provided. 

Dr. Joseph reports no relevant financial involvements; several advisory co-authors report financial involvements with pharmaceutical companies. Dr. Pagidipati reports relevant financial involvement with pharmaceutical companies. Dr. Hayek, Dr. Drake, and Dr. Shah report no relevant financial involvements. Dr. Joseph is an author of the advisory. Dr. Pagidipati, Dr. Hayek, Dr. Drake, and Dr. Shah were not involved in the writing of the advisory.

A version of this article appeared on Medscape.com.

Primary care clinicians play a central role in maintaining the cardiovascular-kidney-metabolic (CKM) health of patients, according to a new advisory from the American Heart Association.

The advisory, published recently in Circulation introduces the concept of CKM health and reevaluates the relationships between obesity, diabetes, kidney disease, and cardiovascular disease (CVD).

“This approach not only raises awareness, it also empowers PCPs to diagnose and treat these conditions more holistically,” Salim Hayek, MD, associate professor of cardiovascular disease and internal medicine, and medical director of the Frankel Cardiovascular Center Clinics at the University of Michigan in Ann Arbor, said in an interview.

 

New CKM Staging, Testing, and Care Strategies

The advisory introduces a new scoring system that ranges from stage 0 (patients with no risk factors for CKM) through stage 4 (patients with clinical CVD in CKM syndrome). Each stage requires specific management strategies and may include screening starting at age 30 years for diabetes, hypertension, and heart failure.

“Stage 0 CKM is usually found in young people, and CKM risk factors and scores typically increase as people age,” said Sean M. Drake, MD, a primary care physician at Henry Ford Health in Sterling Heights, Michigan. 

Dr. Drake advised PCPs to encourage patients who are at stage 0 to maintain ideal cardiovascular health and to monitor those at risk of progressing through the stages.

While PCPs already perform many of the tests the advisory recommends, the conditions overlap and an abnormality in one system should prompt more testing for other conditions. Additional tests, such as urine albumin-creatinine ratio, and more frequent glomerular filtration rate and lipid profile are advised, according to Dr. Drake.

“There also appears to be a role for additional cardiac testing, including echocardiograms and coronary CT scans, and for liver fibrosis screening,” Dr. Drake said. “Medications such as SGLT2 inhibitors, GLP-1 receptor agonists, and ACE inhibitors, beyond current routine use, are emphasized.” 

To better characterize body composition and help diagnose metabolic syndrome, the advisory also recommends measuring waist circumference, which is not routine practice, noted Joshua J. Joseph, MD, MPH, an associate professor of endocrinology, diabetes, and metabolism at The Ohio State University Wexner Medical Center in Columbus, and a co-author of the advisory. 

Recognizing the interconnected nature of cardiac, kidney, and metabolic diseases encourages a shift in mindset for clinicians, according to Neha Pagidipati, MD, MPH, a cardiologist at Duke Health in Durham, North Carolina.

“We have often been trained to focus on the specific problem in front of us,” Dr. Pagidipati said. “We need to be hyper-aware that many patients we see are at risk for multiple CKM entities. We need to be proactive about screening for and treating these when appropriate.”

The advisory emphasizes the need for CKM coordinators to support teams of clinicians from primary care, cardiology, endocrinology, nephrology, nursing, and pharmacy, as well as social workers, care navigators, or community health workers, Dr. Joseph said. 

“The advisory repositions the PCP at the forefront of CKM care coordination, marking a departure from the traditional model where subspecialists primarily manage complications,” Dr. Hayek added.
 

Changes to Payment

The new recommendations are consistent with current management guidelines for obesity, hypertriglyceridemia, hypertension, type 2 diabetes, and chronic kidney disease. 

“The advisory provides integrated algorithms for cardiovascular prevention and management, with specific therapeutic guidance tied to CKM stages, bringing together the current evidence for best practices from the various guidelines and filling gaps in a unified approach,” Dr. Joseph said. 

In addition, the advisory draws attention to the care of younger patients, who may be at increased risk for cardiovascular disease due to lifestyle factors, according to Nishant Shah, MD, assistant professor of medicine at Duke. 

“It considers barriers to care that prevent people from optimizing their cardiovascular health,” Dr. Shah said. 

Although the advisory does not specify proposed payment changes to support the new care model, the move towards value-based care may require billing practices that accommodate integrated care as well as more frequent and more specialized testing, Dr. Hayek said. 

“The advisory is an empowering tool for PCPs, underscoring their critical role in healthcare,” Dr. Hayek said. “It encourages PCPs to advocate for integrated care within their practices and to consider workflow adjustments that enhance the identification and initiation of preventive care for at-risk patients.”

Funding information was not provided. 

Dr. Joseph reports no relevant financial involvements; several advisory co-authors report financial involvements with pharmaceutical companies. Dr. Pagidipati reports relevant financial involvement with pharmaceutical companies. Dr. Hayek, Dr. Drake, and Dr. Shah report no relevant financial involvements. Dr. Joseph is an author of the advisory. Dr. Pagidipati, Dr. Hayek, Dr. Drake, and Dr. Shah were not involved in the writing of the advisory.

A version of this article appeared on Medscape.com.

Primary care clinicians play a central role in maintaining the cardiovascular-kidney-metabolic (CKM) health of patients, according to a new advisory from the American Heart Association.

The advisory, published recently in Circulation introduces the concept of CKM health and reevaluates the relationships between obesity, diabetes, kidney disease, and cardiovascular disease (CVD).

“This approach not only raises awareness, it also empowers PCPs to diagnose and treat these conditions more holistically,” Salim Hayek, MD, associate professor of cardiovascular disease and internal medicine, and medical director of the Frankel Cardiovascular Center Clinics at the University of Michigan in Ann Arbor, said in an interview.

 

New CKM Staging, Testing, and Care Strategies

The advisory introduces a new scoring system that ranges from stage 0 (patients with no risk factors for CKM) through stage 4 (patients with clinical CVD in CKM syndrome). Each stage requires specific management strategies and may include screening starting at age 30 years for diabetes, hypertension, and heart failure.

“Stage 0 CKM is usually found in young people, and CKM risk factors and scores typically increase as people age,” said Sean M. Drake, MD, a primary care physician at Henry Ford Health in Sterling Heights, Michigan. 

Dr. Drake advised PCPs to encourage patients who are at stage 0 to maintain ideal cardiovascular health and to monitor those at risk of progressing through the stages.

While PCPs already perform many of the tests the advisory recommends, the conditions overlap and an abnormality in one system should prompt more testing for other conditions. Additional tests, such as urine albumin-creatinine ratio, and more frequent glomerular filtration rate and lipid profile are advised, according to Dr. Drake.

“There also appears to be a role for additional cardiac testing, including echocardiograms and coronary CT scans, and for liver fibrosis screening,” Dr. Drake said. “Medications such as SGLT2 inhibitors, GLP-1 receptor agonists, and ACE inhibitors, beyond current routine use, are emphasized.” 

To better characterize body composition and help diagnose metabolic syndrome, the advisory also recommends measuring waist circumference, which is not routine practice, noted Joshua J. Joseph, MD, MPH, an associate professor of endocrinology, diabetes, and metabolism at The Ohio State University Wexner Medical Center in Columbus, and a co-author of the advisory. 

Recognizing the interconnected nature of cardiac, kidney, and metabolic diseases encourages a shift in mindset for clinicians, according to Neha Pagidipati, MD, MPH, a cardiologist at Duke Health in Durham, North Carolina.

“We have often been trained to focus on the specific problem in front of us,” Dr. Pagidipati said. “We need to be hyper-aware that many patients we see are at risk for multiple CKM entities. We need to be proactive about screening for and treating these when appropriate.”

The advisory emphasizes the need for CKM coordinators to support teams of clinicians from primary care, cardiology, endocrinology, nephrology, nursing, and pharmacy, as well as social workers, care navigators, or community health workers, Dr. Joseph said. 

“The advisory repositions the PCP at the forefront of CKM care coordination, marking a departure from the traditional model where subspecialists primarily manage complications,” Dr. Hayek added.
 

Changes to Payment

The new recommendations are consistent with current management guidelines for obesity, hypertriglyceridemia, hypertension, type 2 diabetes, and chronic kidney disease. 

“The advisory provides integrated algorithms for cardiovascular prevention and management, with specific therapeutic guidance tied to CKM stages, bringing together the current evidence for best practices from the various guidelines and filling gaps in a unified approach,” Dr. Joseph said. 

In addition, the advisory draws attention to the care of younger patients, who may be at increased risk for cardiovascular disease due to lifestyle factors, according to Nishant Shah, MD, assistant professor of medicine at Duke. 

“It considers barriers to care that prevent people from optimizing their cardiovascular health,” Dr. Shah said. 

Although the advisory does not specify proposed payment changes to support the new care model, the move towards value-based care may require billing practices that accommodate integrated care as well as more frequent and more specialized testing, Dr. Hayek said. 

“The advisory is an empowering tool for PCPs, underscoring their critical role in healthcare,” Dr. Hayek said. “It encourages PCPs to advocate for integrated care within their practices and to consider workflow adjustments that enhance the identification and initiation of preventive care for at-risk patients.”

Funding information was not provided. 

Dr. Joseph reports no relevant financial involvements; several advisory co-authors report financial involvements with pharmaceutical companies. Dr. Pagidipati reports relevant financial involvement with pharmaceutical companies. Dr. Hayek, Dr. Drake, and Dr. Shah report no relevant financial involvements. Dr. Joseph is an author of the advisory. Dr. Pagidipati, Dr. Hayek, Dr. Drake, and Dr. Shah were not involved in the writing of the advisory.

A version of this article appeared on Medscape.com.

A recent article hypothesized that fructose causes more metabolic disease than does sucrose when overfed in the human diet. Fructose intake as high-fructose corn syrup (HFCS) has risen since its use in soft drinks in the United States and parallels the increase in the prevalence of obesity.

The newest hypothesis regarding fructose invokes a genetic survival of the fittest rationale for how fructose-enhanced fat deposition exacerbates the increased caloric consumption from the Western diet to promote metabolic disease especially in our adolescent and young adult population. This theory suggests that fructose consumption causes low adenosine triphosphate, which stimulates energy intake causing an imbalance of energy regulation.

Ongoing interest in the association between the increased use of HFCS and the prevalence of obesity in the United States continues. The use of HFCS in sugary sweetened beverages (SSBs) has reduced the cost of these beverages because of technology in preparing HFCS from corn and the substitution of the cheaper HFCS for sugar in SSBs. Although SSBs haven’t been proven to cause obesity, there has been an increase in the risk for type 2 diabetes, cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and even cancer. Research in HFCS, weight gain, and metabolic disease continues despite little definitive evidence of causation.

The relationship between SSBs consumption and obesity has been attributed to the increase in overall total caloric intake of the diet. These liquid calories do not suppress the intake of other foods to equalize the total amount of calories ingested. This knowledge has been gleaned from work performed by R. Mattes and B. Rolls in the 1990s through the early 2000s.

This research and the current work on HFCS and metabolic disease is important because there are adolescents and young adults in the United States and globally that ingest a large amount of SSBs and therefore are at risk for metabolic disease, type 2 diabetes, NAFLD, and CVD at an early age.

The concern over fructose stems from the association between the advent of increasing HFCS in SSBs and the increase in prevalence of obesity occurring at similar time periods in the United States, around 1970-1980.

Researchers noted the association and began to focus on potential reasons to pinpoint HFCS or fructose itself so we have a mechanism of action specific to fructose. Therefore, the public could be warned about the risk of drinking SSBs due to the HFCS and fructose ingested and the possibility of metabolic disease. Perhaps, there is a method to remove harmful HFCS from the food supply much like what has happened with industrially produced trans fatty acids. In 2018, the World Health Organization called for a total ban on trans fats due to causation of 500 million early deaths per year globally.

Similar to the process of making HFCS, most trans fats are formed through an industrial process that alters vegetable oil and creates a shelf stable inexpensive partially hydrogenated oil. Trans fats have been shown to increase low-density lipoprotein (LDL) cholesterol and decrease high-density lipoprotein (HDL) increasing the risk for myocardial infarction and stroke.

The prevalence of obesity has increased worldwide, even in countries where SSBs do not contain HFCS.

Still, the proof that HFCS can override the satiety pathway and cause excess calorie intake is intriguing and may have teeth if we can pinpoint the increase in prevalence of obesity in children and adolescents on increased ingestion of HFCS in SSBs. There is no reason nutritionally to add sugar or HFCS to liquids. Plus, if HFCS has a metabolic disadvantage then all the more reason to ban it. Then, it becomes like trans fats: a toxin in the food supply.


Dr. Apovian is a Faculty Member, Department of Medicine; Co-Director, Center for Weight Management and Wellness, Section of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. She has disclosed financial relationships with Altimmune, Inc; Cowen and Company, LLC; Currax Pharmaceuticals, LLC; EPG Communication Holdings, Ltd; Gelesis, Srl; L-Nutra, Inc; NeuroBo Pharmaceuticals; and Novo Nordisk, Inc. She has received research grants from the National Institutes of Health; Patient-Centered Outcomes Research Institute; GI Dynamics, Inc.

A version of this article appeared on Medscape.com.

A recent article hypothesized that fructose causes more metabolic disease than does sucrose when overfed in the human diet. Fructose intake as high-fructose corn syrup (HFCS) has risen since its use in soft drinks in the United States and parallels the increase in the prevalence of obesity.

The newest hypothesis regarding fructose invokes a genetic survival of the fittest rationale for how fructose-enhanced fat deposition exacerbates the increased caloric consumption from the Western diet to promote metabolic disease especially in our adolescent and young adult population. This theory suggests that fructose consumption causes low adenosine triphosphate, which stimulates energy intake causing an imbalance of energy regulation.

Ongoing interest in the association between the increased use of HFCS and the prevalence of obesity in the United States continues. The use of HFCS in sugary sweetened beverages (SSBs) has reduced the cost of these beverages because of technology in preparing HFCS from corn and the substitution of the cheaper HFCS for sugar in SSBs. Although SSBs haven’t been proven to cause obesity, there has been an increase in the risk for type 2 diabetes, cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and even cancer. Research in HFCS, weight gain, and metabolic disease continues despite little definitive evidence of causation.

The relationship between SSBs consumption and obesity has been attributed to the increase in overall total caloric intake of the diet. These liquid calories do not suppress the intake of other foods to equalize the total amount of calories ingested. This knowledge has been gleaned from work performed by R. Mattes and B. Rolls in the 1990s through the early 2000s.

This research and the current work on HFCS and metabolic disease is important because there are adolescents and young adults in the United States and globally that ingest a large amount of SSBs and therefore are at risk for metabolic disease, type 2 diabetes, NAFLD, and CVD at an early age.

The concern over fructose stems from the association between the advent of increasing HFCS in SSBs and the increase in prevalence of obesity occurring at similar time periods in the United States, around 1970-1980.

Researchers noted the association and began to focus on potential reasons to pinpoint HFCS or fructose itself so we have a mechanism of action specific to fructose. Therefore, the public could be warned about the risk of drinking SSBs due to the HFCS and fructose ingested and the possibility of metabolic disease. Perhaps, there is a method to remove harmful HFCS from the food supply much like what has happened with industrially produced trans fatty acids. In 2018, the World Health Organization called for a total ban on trans fats due to causation of 500 million early deaths per year globally.

Similar to the process of making HFCS, most trans fats are formed through an industrial process that alters vegetable oil and creates a shelf stable inexpensive partially hydrogenated oil. Trans fats have been shown to increase low-density lipoprotein (LDL) cholesterol and decrease high-density lipoprotein (HDL) increasing the risk for myocardial infarction and stroke.

The prevalence of obesity has increased worldwide, even in countries where SSBs do not contain HFCS.

Still, the proof that HFCS can override the satiety pathway and cause excess calorie intake is intriguing and may have teeth if we can pinpoint the increase in prevalence of obesity in children and adolescents on increased ingestion of HFCS in SSBs. There is no reason nutritionally to add sugar or HFCS to liquids. Plus, if HFCS has a metabolic disadvantage then all the more reason to ban it. Then, it becomes like trans fats: a toxin in the food supply.


Dr. Apovian is a Faculty Member, Department of Medicine; Co-Director, Center for Weight Management and Wellness, Section of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. She has disclosed financial relationships with Altimmune, Inc; Cowen and Company, LLC; Currax Pharmaceuticals, LLC; EPG Communication Holdings, Ltd; Gelesis, Srl; L-Nutra, Inc; NeuroBo Pharmaceuticals; and Novo Nordisk, Inc. She has received research grants from the National Institutes of Health; Patient-Centered Outcomes Research Institute; GI Dynamics, Inc.

A version of this article appeared on Medscape.com.

A recent article hypothesized that fructose causes more metabolic disease than does sucrose when overfed in the human diet. Fructose intake as high-fructose corn syrup (HFCS) has risen since its use in soft drinks in the United States and parallels the increase in the prevalence of obesity.

The newest hypothesis regarding fructose invokes a genetic survival of the fittest rationale for how fructose-enhanced fat deposition exacerbates the increased caloric consumption from the Western diet to promote metabolic disease especially in our adolescent and young adult population. This theory suggests that fructose consumption causes low adenosine triphosphate, which stimulates energy intake causing an imbalance of energy regulation.

Ongoing interest in the association between the increased use of HFCS and the prevalence of obesity in the United States continues. The use of HFCS in sugary sweetened beverages (SSBs) has reduced the cost of these beverages because of technology in preparing HFCS from corn and the substitution of the cheaper HFCS for sugar in SSBs. Although SSBs haven’t been proven to cause obesity, there has been an increase in the risk for type 2 diabetes, cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and even cancer. Research in HFCS, weight gain, and metabolic disease continues despite little definitive evidence of causation.

The relationship between SSBs consumption and obesity has been attributed to the increase in overall total caloric intake of the diet. These liquid calories do not suppress the intake of other foods to equalize the total amount of calories ingested. This knowledge has been gleaned from work performed by R. Mattes and B. Rolls in the 1990s through the early 2000s.

This research and the current work on HFCS and metabolic disease is important because there are adolescents and young adults in the United States and globally that ingest a large amount of SSBs and therefore are at risk for metabolic disease, type 2 diabetes, NAFLD, and CVD at an early age.

The concern over fructose stems from the association between the advent of increasing HFCS in SSBs and the increase in prevalence of obesity occurring at similar time periods in the United States, around 1970-1980.

Researchers noted the association and began to focus on potential reasons to pinpoint HFCS or fructose itself so we have a mechanism of action specific to fructose. Therefore, the public could be warned about the risk of drinking SSBs due to the HFCS and fructose ingested and the possibility of metabolic disease. Perhaps, there is a method to remove harmful HFCS from the food supply much like what has happened with industrially produced trans fatty acids. In 2018, the World Health Organization called for a total ban on trans fats due to causation of 500 million early deaths per year globally.

Similar to the process of making HFCS, most trans fats are formed through an industrial process that alters vegetable oil and creates a shelf stable inexpensive partially hydrogenated oil. Trans fats have been shown to increase low-density lipoprotein (LDL) cholesterol and decrease high-density lipoprotein (HDL) increasing the risk for myocardial infarction and stroke.

The prevalence of obesity has increased worldwide, even in countries where SSBs do not contain HFCS.

Still, the proof that HFCS can override the satiety pathway and cause excess calorie intake is intriguing and may have teeth if we can pinpoint the increase in prevalence of obesity in children and adolescents on increased ingestion of HFCS in SSBs. There is no reason nutritionally to add sugar or HFCS to liquids. Plus, if HFCS has a metabolic disadvantage then all the more reason to ban it. Then, it becomes like trans fats: a toxin in the food supply.


Dr. Apovian is a Faculty Member, Department of Medicine; Co-Director, Center for Weight Management and Wellness, Section of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. She has disclosed financial relationships with Altimmune, Inc; Cowen and Company, LLC; Currax Pharmaceuticals, LLC; EPG Communication Holdings, Ltd; Gelesis, Srl; L-Nutra, Inc; NeuroBo Pharmaceuticals; and Novo Nordisk, Inc. She has received research grants from the National Institutes of Health; Patient-Centered Outcomes Research Institute; GI Dynamics, Inc.

A version of this article appeared on Medscape.com.

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

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

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

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

Severe Gastric Problems

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

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

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

Anesthetic Complications

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

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

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

Increased Suicidality Risk?

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

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

Long-Term Safety

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

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

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

Awaiting Guideline Updates

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

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

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

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

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

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

Severe Gastric Problems

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

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

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

Anesthetic Complications

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

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

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

Increased Suicidality Risk?

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

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

Long-Term Safety

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

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

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

Awaiting Guideline Updates

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

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

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

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

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

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

Severe Gastric Problems

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

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

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

Anesthetic Complications

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

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

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

Increased Suicidality Risk?

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

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

Long-Term Safety

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

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

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

Awaiting Guideline Updates

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

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

Bariatric surgery continues to play a major role in obesity management despite the emergence of potent new weight-loss medications, according to two experts who spoke at an Endocrine Society science writers briefing.

“Bariatric surgery is safe, effective, and unfortunately underutilized for treating obesity and its complications,” said Jaime Almandoz, MD, medical director of the Weight Wellness Program at the University of Texas Southwestern Medical Center, Dallas.

Added Dr. Almandoz, who is triple board-certified in internal medicine, endocrinology, and obesity medicine, “Sometimes this gets presented in a linear fashion. ‘We’ll try lifestyle first, and if that doesn’t work, we’ll try medications, and if that doesn’t work, we’ll try surgery.’ But sometimes we might need to go straight to surgery instead of going through medications first, because it may be the most effective and evidence-based treatment for the person in the office in front of you.”

Moreover, he pointed out that currently, Medicare and many private insurers don’t cover antiobesity medications but do cover bariatric surgery.

Indeed, Srividya Kidambi, MD, professor and chief of endocrinology and molecular medicine at the Medical College of Wisconsin/Froedtert Hospital, Milwaukee, said there are certain types of patients for whom she might consider bariatric surgery first. One would be a person with a body mass index (BMI) greater than 40 kg/m² or with a BMI greater than 35 kg/m² and severe comorbidities.

Another, she said, would be young, relatively healthy people with obesity who have no comorbid conditions. “We know that if we stop the medication, the weight comes back. So, if I see a 20- to 25-year-old, am I really to commit them to lifelong therapy, or is bariatric surgery a better option in these cases? These drugs have not been around that long ... so I tend to recommend bariatric surgery in some patients.”

During the recent briefing, Dr. Almandoz summarized the evidence base for the benefits of bariatric surgery beyond weight loss, which include remission of type 2 diabetes and fatty liver disease, reduction of the risks of cardiovascular disease and cancer, and increased life expectancy.

“Everyone seems to be talking about GLP-1s for facilitating weight loss and treating obesity. ... What I want to do is provide a counterpoint to accessible therapies that are covered by more insurance plans and that may, in fact, have a better evidence base for treating obesity and its related complications,” he said in his introduction.

Bariatric surgery has been used for decades, and many centers of excellence perform it, with greatly reduced complication rates seen today than in the past. “It’s comparable to having a gallbladder surgery in terms of perioperative risk,” he noted.

Medicare and private insurers generally cover bariatric surgery for people with BMI greater than 40 kg/m2 or 35-39 kg/m² and at least one weight-related comorbidity, including type 2 diabetes, obstructive sleep apnea, hypertension, atherosclerotic disease, hyperlipidemia, and fatty liver disease.

Data suggest that weight reduction of about 3% can lead to meaningful reductions in blood glucose and triglyceride levels, but weight loss of 15% or greater is associated with reductions in cardiovascular events and type 2 diabetes remission. Lifestyle modification typically produces about 5% weight loss, compared with 20%-35% with bariatric surgery with sleeve gastrectomy or gastric bypass.

Older weight loss medications produced weight loss of 5%-10%; only the newer medications, semaglutide 2.4 mg and tirzepatide, come close to that. Weight loss with semaglutide is about 15%, while tirzepatide can produce weight loss of up to 22%. But, there are still issues with affordability, access, and lack of coverage, Dr. Almandoz noted.

One recent randomized trial of more than 400 individuals showed that bariatric surgery was more effective than lifestyle and medical therapies for treating metabolic-associated steatohepatitis without worsening of fibrosis.

Another showed that the surgery was associated with fewer major adverse liver outcomes among people who already had MASH. That same study showed a 70% reduction in cardiovascular events with bariatric surgery.

For patients with type 2 diabetes, numerous trials have demonstrated long-term remission and reduced A1c at 5 years and 10 years post surgery, along with reductions in microvascular and macrovascular complications.

Other data suggest that a shorter history of type 2 diabetes is among the factors predicting remission with bariatric surgery. “Oftentimes, both patients and providers will wait until the diabetes is quite advanced before they even have the conversation about weight loss or even bariatric surgery. This suggests that if we intervene earlier in the course of disease, when it is less severe and less advanced, we have a higher rate of causing remission in the diabetes,” Dr. Almandoz said.

The American Diabetes Association’s Standards of Care incorporate bariatric surgery as either “recommended” or “may be considered” to treat type 2 diabetes, depending on BMI level, for those who don’t achieve durable weight loss with nonsurgical methods, he noted.

A retrospective cohort study showed significant reductions in cardiovascular outcomes with bariatric surgery among people with baseline cardiovascular disease. “This is not just about bariatric surgery to cause weight loss. This is about the multitude of effects that happen when we treat obesity as a disease with highly effective therapies such as surgery,” he said.

Even cancer risk and cancer-related mortality were significantly reduced with bariatric surgery, another study found.

And in the long-term Swedish Obese Subjects Study, among people with obesity, bariatric surgery was associated with a 3-year increase in life expectancy, compared with not undergoing surgery.

However, Dr. Almandoz also pointed out that some patients may benefit from both weight-loss medication and bariatric surgery. “Once someone has undergone pharmacotherapy, there may still be a role for bariatric procedures in helping to optimize body weight and control body weight long term. And likewise for those who have undergone bariatric surgery, there’s also a role for pharmacotherapy in terms of treating insufficient weight loss or weight recurrence after bariatric surgery. ... So I think there’s clearly a role for integration of therapies.”

Dr. Almandoz serves as consultant/advisory board member for Novo Nordisk, Boehringer Ingelheim, and Eli Lilly. Dr. Kidambi is director of TOPS Center for Metabolic Research and is medical editor of TOPS Magazine, for which her institution receives an honorarium.

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

Bariatric surgery continues to play a major role in obesity management despite the emergence of potent new weight-loss medications, according to two experts who spoke at an Endocrine Society science writers briefing.

“Bariatric surgery is safe, effective, and unfortunately underutilized for treating obesity and its complications,” said Jaime Almandoz, MD, medical director of the Weight Wellness Program at the University of Texas Southwestern Medical Center, Dallas.

Added Dr. Almandoz, who is triple board-certified in internal medicine, endocrinology, and obesity medicine, “Sometimes this gets presented in a linear fashion. ‘We’ll try lifestyle first, and if that doesn’t work, we’ll try medications, and if that doesn’t work, we’ll try surgery.’ But sometimes we might need to go straight to surgery instead of going through medications first, because it may be the most effective and evidence-based treatment for the person in the office in front of you.”

Moreover, he pointed out that currently, Medicare and many private insurers don’t cover antiobesity medications but do cover bariatric surgery.

Indeed, Srividya Kidambi, MD, professor and chief of endocrinology and molecular medicine at the Medical College of Wisconsin/Froedtert Hospital, Milwaukee, said there are certain types of patients for whom she might consider bariatric surgery first. One would be a person with a body mass index (BMI) greater than 40 kg/m² or with a BMI greater than 35 kg/m² and severe comorbidities.

Another, she said, would be young, relatively healthy people with obesity who have no comorbid conditions. “We know that if we stop the medication, the weight comes back. So, if I see a 20- to 25-year-old, am I really to commit them to lifelong therapy, or is bariatric surgery a better option in these cases? These drugs have not been around that long ... so I tend to recommend bariatric surgery in some patients.”

During the recent briefing, Dr. Almandoz summarized the evidence base for the benefits of bariatric surgery beyond weight loss, which include remission of type 2 diabetes and fatty liver disease, reduction of the risks of cardiovascular disease and cancer, and increased life expectancy.

“Everyone seems to be talking about GLP-1s for facilitating weight loss and treating obesity. ... What I want to do is provide a counterpoint to accessible therapies that are covered by more insurance plans and that may, in fact, have a better evidence base for treating obesity and its related complications,” he said in his introduction.

Bariatric surgery has been used for decades, and many centers of excellence perform it, with greatly reduced complication rates seen today than in the past. “It’s comparable to having a gallbladder surgery in terms of perioperative risk,” he noted.

Medicare and private insurers generally cover bariatric surgery for people with BMI greater than 40 kg/m2 or 35-39 kg/m² and at least one weight-related comorbidity, including type 2 diabetes, obstructive sleep apnea, hypertension, atherosclerotic disease, hyperlipidemia, and fatty liver disease.

Data suggest that weight reduction of about 3% can lead to meaningful reductions in blood glucose and triglyceride levels, but weight loss of 15% or greater is associated with reductions in cardiovascular events and type 2 diabetes remission. Lifestyle modification typically produces about 5% weight loss, compared with 20%-35% with bariatric surgery with sleeve gastrectomy or gastric bypass.

Older weight loss medications produced weight loss of 5%-10%; only the newer medications, semaglutide 2.4 mg and tirzepatide, come close to that. Weight loss with semaglutide is about 15%, while tirzepatide can produce weight loss of up to 22%. But, there are still issues with affordability, access, and lack of coverage, Dr. Almandoz noted.

One recent randomized trial of more than 400 individuals showed that bariatric surgery was more effective than lifestyle and medical therapies for treating metabolic-associated steatohepatitis without worsening of fibrosis.

Another showed that the surgery was associated with fewer major adverse liver outcomes among people who already had MASH. That same study showed a 70% reduction in cardiovascular events with bariatric surgery.

For patients with type 2 diabetes, numerous trials have demonstrated long-term remission and reduced A1c at 5 years and 10 years post surgery, along with reductions in microvascular and macrovascular complications.

Other data suggest that a shorter history of type 2 diabetes is among the factors predicting remission with bariatric surgery. “Oftentimes, both patients and providers will wait until the diabetes is quite advanced before they even have the conversation about weight loss or even bariatric surgery. This suggests that if we intervene earlier in the course of disease, when it is less severe and less advanced, we have a higher rate of causing remission in the diabetes,” Dr. Almandoz said.

The American Diabetes Association’s Standards of Care incorporate bariatric surgery as either “recommended” or “may be considered” to treat type 2 diabetes, depending on BMI level, for those who don’t achieve durable weight loss with nonsurgical methods, he noted.

A retrospective cohort study showed significant reductions in cardiovascular outcomes with bariatric surgery among people with baseline cardiovascular disease. “This is not just about bariatric surgery to cause weight loss. This is about the multitude of effects that happen when we treat obesity as a disease with highly effective therapies such as surgery,” he said.

Even cancer risk and cancer-related mortality were significantly reduced with bariatric surgery, another study found.

And in the long-term Swedish Obese Subjects Study, among people with obesity, bariatric surgery was associated with a 3-year increase in life expectancy, compared with not undergoing surgery.

However, Dr. Almandoz also pointed out that some patients may benefit from both weight-loss medication and bariatric surgery. “Once someone has undergone pharmacotherapy, there may still be a role for bariatric procedures in helping to optimize body weight and control body weight long term. And likewise for those who have undergone bariatric surgery, there’s also a role for pharmacotherapy in terms of treating insufficient weight loss or weight recurrence after bariatric surgery. ... So I think there’s clearly a role for integration of therapies.”

Dr. Almandoz serves as consultant/advisory board member for Novo Nordisk, Boehringer Ingelheim, and Eli Lilly. Dr. Kidambi is director of TOPS Center for Metabolic Research and is medical editor of TOPS Magazine, for which her institution receives an honorarium.

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

Bariatric surgery continues to play a major role in obesity management despite the emergence of potent new weight-loss medications, according to two experts who spoke at an Endocrine Society science writers briefing.

“Bariatric surgery is safe, effective, and unfortunately underutilized for treating obesity and its complications,” said Jaime Almandoz, MD, medical director of the Weight Wellness Program at the University of Texas Southwestern Medical Center, Dallas.

Added Dr. Almandoz, who is triple board-certified in internal medicine, endocrinology, and obesity medicine, “Sometimes this gets presented in a linear fashion. ‘We’ll try lifestyle first, and if that doesn’t work, we’ll try medications, and if that doesn’t work, we’ll try surgery.’ But sometimes we might need to go straight to surgery instead of going through medications first, because it may be the most effective and evidence-based treatment for the person in the office in front of you.”

Moreover, he pointed out that currently, Medicare and many private insurers don’t cover antiobesity medications but do cover bariatric surgery.

Indeed, Srividya Kidambi, MD, professor and chief of endocrinology and molecular medicine at the Medical College of Wisconsin/Froedtert Hospital, Milwaukee, said there are certain types of patients for whom she might consider bariatric surgery first. One would be a person with a body mass index (BMI) greater than 40 kg/m² or with a BMI greater than 35 kg/m² and severe comorbidities.

Another, she said, would be young, relatively healthy people with obesity who have no comorbid conditions. “We know that if we stop the medication, the weight comes back. So, if I see a 20- to 25-year-old, am I really to commit them to lifelong therapy, or is bariatric surgery a better option in these cases? These drugs have not been around that long ... so I tend to recommend bariatric surgery in some patients.”

During the recent briefing, Dr. Almandoz summarized the evidence base for the benefits of bariatric surgery beyond weight loss, which include remission of type 2 diabetes and fatty liver disease, reduction of the risks of cardiovascular disease and cancer, and increased life expectancy.

“Everyone seems to be talking about GLP-1s for facilitating weight loss and treating obesity. ... What I want to do is provide a counterpoint to accessible therapies that are covered by more insurance plans and that may, in fact, have a better evidence base for treating obesity and its related complications,” he said in his introduction.

Bariatric surgery has been used for decades, and many centers of excellence perform it, with greatly reduced complication rates seen today than in the past. “It’s comparable to having a gallbladder surgery in terms of perioperative risk,” he noted.

Medicare and private insurers generally cover bariatric surgery for people with BMI greater than 40 kg/m2 or 35-39 kg/m² and at least one weight-related comorbidity, including type 2 diabetes, obstructive sleep apnea, hypertension, atherosclerotic disease, hyperlipidemia, and fatty liver disease.

Data suggest that weight reduction of about 3% can lead to meaningful reductions in blood glucose and triglyceride levels, but weight loss of 15% or greater is associated with reductions in cardiovascular events and type 2 diabetes remission. Lifestyle modification typically produces about 5% weight loss, compared with 20%-35% with bariatric surgery with sleeve gastrectomy or gastric bypass.

Older weight loss medications produced weight loss of 5%-10%; only the newer medications, semaglutide 2.4 mg and tirzepatide, come close to that. Weight loss with semaglutide is about 15%, while tirzepatide can produce weight loss of up to 22%. But, there are still issues with affordability, access, and lack of coverage, Dr. Almandoz noted.

One recent randomized trial of more than 400 individuals showed that bariatric surgery was more effective than lifestyle and medical therapies for treating metabolic-associated steatohepatitis without worsening of fibrosis.

Another showed that the surgery was associated with fewer major adverse liver outcomes among people who already had MASH. That same study showed a 70% reduction in cardiovascular events with bariatric surgery.

For patients with type 2 diabetes, numerous trials have demonstrated long-term remission and reduced A1c at 5 years and 10 years post surgery, along with reductions in microvascular and macrovascular complications.

Other data suggest that a shorter history of type 2 diabetes is among the factors predicting remission with bariatric surgery. “Oftentimes, both patients and providers will wait until the diabetes is quite advanced before they even have the conversation about weight loss or even bariatric surgery. This suggests that if we intervene earlier in the course of disease, when it is less severe and less advanced, we have a higher rate of causing remission in the diabetes,” Dr. Almandoz said.

The American Diabetes Association’s Standards of Care incorporate bariatric surgery as either “recommended” or “may be considered” to treat type 2 diabetes, depending on BMI level, for those who don’t achieve durable weight loss with nonsurgical methods, he noted.

A retrospective cohort study showed significant reductions in cardiovascular outcomes with bariatric surgery among people with baseline cardiovascular disease. “This is not just about bariatric surgery to cause weight loss. This is about the multitude of effects that happen when we treat obesity as a disease with highly effective therapies such as surgery,” he said.

Even cancer risk and cancer-related mortality were significantly reduced with bariatric surgery, another study found.

And in the long-term Swedish Obese Subjects Study, among people with obesity, bariatric surgery was associated with a 3-year increase in life expectancy, compared with not undergoing surgery.

However, Dr. Almandoz also pointed out that some patients may benefit from both weight-loss medication and bariatric surgery. “Once someone has undergone pharmacotherapy, there may still be a role for bariatric procedures in helping to optimize body weight and control body weight long term. And likewise for those who have undergone bariatric surgery, there’s also a role for pharmacotherapy in terms of treating insufficient weight loss or weight recurrence after bariatric surgery. ... So I think there’s clearly a role for integration of therapies.”

Dr. Almandoz serves as consultant/advisory board member for Novo Nordisk, Boehringer Ingelheim, and Eli Lilly. Dr. Kidambi is director of TOPS Center for Metabolic Research and is medical editor of TOPS Magazine, for which her institution receives an honorarium.

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

I cock my head at my “new” patient, Sherri, who heads into my consultation room at 8:30 on a rainy Monday morning. She looks vaguely familiar but I can’t quite place her face. “Dr. Messer,” she cries, “don’t you remember me? I was one of your very first patients 15 years ago in Westchester. You had just finished training.” Suddenly it all comes back to me.

Meeting Sherri reminded me of the lesson in humility that my mentor, Dr. Alice Levine, taught our crowded lecture hall so many years ago. Once upon a time, she prided herself on being an infinitely important doctor. One day, she met a patient with empty sella syndrome (literally missing his whole pituitary gland – MRI proven). She fully expected to swoop in to save the patient’s life by expertly replacing each absconded pituitary hormone, but to her shock and delight, an invisible little sliver of pituitary left in his brain allowed him to magically eek out completely normal hormone levels.

Sherri walked into my office so many years ago with a body mass index in the mid-40s. In laymen’s terms, she was morbidly obese. I settled in to discuss her hypertension, diabetes, high cholesterol, fatty liver, polycystic ovary syndrome, etc., but to my shock and delight, her blood pressure and blood work were completely normal. I struggled to keep a neutral face. She was there to discuss hair loss. I had just met my first patient with metabolically healthy obesity (MHO), and I was floored.

Fast-forward 15 years. Sherri sits down across the desk from me and hands me her blood work. Her formerly pristine labs are now peppered with red exclamation points and critically high lab values. Sherri had transitioned from MHO to metabolically unhealthy obesity (MUO).

Early clinical trials concluded that it was possible to have obesity but be metabolically healthy. Approximately 15% of patients living with obesity lack any of the comorbidities typically associated with this phenotype. These findings contributed to the de-emphasis on obesity as a true disease state.

In retrospect, the MHO subtype appears to be much more common in the younger and more active population and is typically quite transient. A new study published in Diabetes, Obesity and Metabolism revealed that people with MHO are 1.5 times more likely to develop diabetes vs. metabolically healthy normal-weight individuals. In addition, people living with obesity and no known metabolic complications still had a 50% higher risk for coronary artery disease. The study also showed that over 50% of people initially characterized as MHO eventually became MUO after a 16-year follow-up.

So once again, all roads lead to semaglutide (Wegovy), the most effective U.S. Food and Drug Administration–approved weight loss medication to date. The incretin class of medications not only helps patients lose 15% or more of their body weight, but it also helps reverse insulin resistance, lower the risk for heart disease, melt away fatty liver, and lower cholesterol levels and blood pressures. While an emphasis on lifestyle changes is always important, these medications are critical adjuncts to conventional therapies.

Sherri’s nearly inevitable transition from MHO to MUO speaks to the pressing need to treat patients living with obesity before the metabolic complications and increased cardiovascular risk develop. Fifteen years ago, I discussed her hair loss for 45 minutes and never mentioned the looming issue. Of course, back then there was no semaglutide or tirzepatide, which was just approved for obesity.

Sherri left our most recent visit with a prescription for Wegovy as well as appointments with a complimentary trainer and dietitian. Now that we have the tools we need, let’s commit to helping our patients achieve true metabolic health. Unlike the magical pituitary patient, metabolically healthy obesity is an illusion – and we owe it to our patients to treat it as such.

Dr. Messer is a clinical assistant professor at Mount Sinai School of Medicine, New York, and an associate professor at Hofstra University, Hempstead, N.Y. She disclosed no relevant conflicts of interest.

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

I cock my head at my “new” patient, Sherri, who heads into my consultation room at 8:30 on a rainy Monday morning. She looks vaguely familiar but I can’t quite place her face. “Dr. Messer,” she cries, “don’t you remember me? I was one of your very first patients 15 years ago in Westchester. You had just finished training.” Suddenly it all comes back to me.

Meeting Sherri reminded me of the lesson in humility that my mentor, Dr. Alice Levine, taught our crowded lecture hall so many years ago. Once upon a time, she prided herself on being an infinitely important doctor. One day, she met a patient with empty sella syndrome (literally missing his whole pituitary gland – MRI proven). She fully expected to swoop in to save the patient’s life by expertly replacing each absconded pituitary hormone, but to her shock and delight, an invisible little sliver of pituitary left in his brain allowed him to magically eek out completely normal hormone levels.

Sherri walked into my office so many years ago with a body mass index in the mid-40s. In laymen’s terms, she was morbidly obese. I settled in to discuss her hypertension, diabetes, high cholesterol, fatty liver, polycystic ovary syndrome, etc., but to my shock and delight, her blood pressure and blood work were completely normal. I struggled to keep a neutral face. She was there to discuss hair loss. I had just met my first patient with metabolically healthy obesity (MHO), and I was floored.

Fast-forward 15 years. Sherri sits down across the desk from me and hands me her blood work. Her formerly pristine labs are now peppered with red exclamation points and critically high lab values. Sherri had transitioned from MHO to metabolically unhealthy obesity (MUO).

Early clinical trials concluded that it was possible to have obesity but be metabolically healthy. Approximately 15% of patients living with obesity lack any of the comorbidities typically associated with this phenotype. These findings contributed to the de-emphasis on obesity as a true disease state.

In retrospect, the MHO subtype appears to be much more common in the younger and more active population and is typically quite transient. A new study published in Diabetes, Obesity and Metabolism revealed that people with MHO are 1.5 times more likely to develop diabetes vs. metabolically healthy normal-weight individuals. In addition, people living with obesity and no known metabolic complications still had a 50% higher risk for coronary artery disease. The study also showed that over 50% of people initially characterized as MHO eventually became MUO after a 16-year follow-up.

So once again, all roads lead to semaglutide (Wegovy), the most effective U.S. Food and Drug Administration–approved weight loss medication to date. The incretin class of medications not only helps patients lose 15% or more of their body weight, but it also helps reverse insulin resistance, lower the risk for heart disease, melt away fatty liver, and lower cholesterol levels and blood pressures. While an emphasis on lifestyle changes is always important, these medications are critical adjuncts to conventional therapies.

Sherri’s nearly inevitable transition from MHO to MUO speaks to the pressing need to treat patients living with obesity before the metabolic complications and increased cardiovascular risk develop. Fifteen years ago, I discussed her hair loss for 45 minutes and never mentioned the looming issue. Of course, back then there was no semaglutide or tirzepatide, which was just approved for obesity.

Sherri left our most recent visit with a prescription for Wegovy as well as appointments with a complimentary trainer and dietitian. Now that we have the tools we need, let’s commit to helping our patients achieve true metabolic health. Unlike the magical pituitary patient, metabolically healthy obesity is an illusion – and we owe it to our patients to treat it as such.

Dr. Messer is a clinical assistant professor at Mount Sinai School of Medicine, New York, and an associate professor at Hofstra University, Hempstead, N.Y. She disclosed no relevant conflicts of interest.

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

I cock my head at my “new” patient, Sherri, who heads into my consultation room at 8:30 on a rainy Monday morning. She looks vaguely familiar but I can’t quite place her face. “Dr. Messer,” she cries, “don’t you remember me? I was one of your very first patients 15 years ago in Westchester. You had just finished training.” Suddenly it all comes back to me.

Meeting Sherri reminded me of the lesson in humility that my mentor, Dr. Alice Levine, taught our crowded lecture hall so many years ago. Once upon a time, she prided herself on being an infinitely important doctor. One day, she met a patient with empty sella syndrome (literally missing his whole pituitary gland – MRI proven). She fully expected to swoop in to save the patient’s life by expertly replacing each absconded pituitary hormone, but to her shock and delight, an invisible little sliver of pituitary left in his brain allowed him to magically eek out completely normal hormone levels.

Sherri walked into my office so many years ago with a body mass index in the mid-40s. In laymen’s terms, she was morbidly obese. I settled in to discuss her hypertension, diabetes, high cholesterol, fatty liver, polycystic ovary syndrome, etc., but to my shock and delight, her blood pressure and blood work were completely normal. I struggled to keep a neutral face. She was there to discuss hair loss. I had just met my first patient with metabolically healthy obesity (MHO), and I was floored.

Fast-forward 15 years. Sherri sits down across the desk from me and hands me her blood work. Her formerly pristine labs are now peppered with red exclamation points and critically high lab values. Sherri had transitioned from MHO to metabolically unhealthy obesity (MUO).

Early clinical trials concluded that it was possible to have obesity but be metabolically healthy. Approximately 15% of patients living with obesity lack any of the comorbidities typically associated with this phenotype. These findings contributed to the de-emphasis on obesity as a true disease state.

In retrospect, the MHO subtype appears to be much more common in the younger and more active population and is typically quite transient. A new study published in Diabetes, Obesity and Metabolism revealed that people with MHO are 1.5 times more likely to develop diabetes vs. metabolically healthy normal-weight individuals. In addition, people living with obesity and no known metabolic complications still had a 50% higher risk for coronary artery disease. The study also showed that over 50% of people initially characterized as MHO eventually became MUO after a 16-year follow-up.

So once again, all roads lead to semaglutide (Wegovy), the most effective U.S. Food and Drug Administration–approved weight loss medication to date. The incretin class of medications not only helps patients lose 15% or more of their body weight, but it also helps reverse insulin resistance, lower the risk for heart disease, melt away fatty liver, and lower cholesterol levels and blood pressures. While an emphasis on lifestyle changes is always important, these medications are critical adjuncts to conventional therapies.

Sherri’s nearly inevitable transition from MHO to MUO speaks to the pressing need to treat patients living with obesity before the metabolic complications and increased cardiovascular risk develop. Fifteen years ago, I discussed her hair loss for 45 minutes and never mentioned the looming issue. Of course, back then there was no semaglutide or tirzepatide, which was just approved for obesity.

Sherri left our most recent visit with a prescription for Wegovy as well as appointments with a complimentary trainer and dietitian. Now that we have the tools we need, let’s commit to helping our patients achieve true metabolic health. Unlike the magical pituitary patient, metabolically healthy obesity is an illusion – and we owe it to our patients to treat it as such.

Dr. Messer is a clinical assistant professor at Mount Sinai School of Medicine, New York, and an associate professor at Hofstra University, Hempstead, N.Y. She disclosed no relevant conflicts of interest.

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

BOSTON – Patients with metabolic-associated steatotic liver disease (MASLD, formerly NAFLD) without cirrhosis who took daily low-dose aspirin in a double-blind randomized trial demonstrated significant reductions in liver fat content over 6 months compared with similar patients who took a placebo, study results show.

“In MASLD without cirrhosis, low-dose aspirin, 81 milligrams daily, led to decreases in liver fat and improved markers of hepatic inflammation and fibrosis,” reported Robert M. Wilechansky, MD, a transplant hepatology fellow at Massachusetts General Hospital in Boston.

“It was safe and well tolerated in this study, but we would like to see larger, longer-term clinical trials to test the efficacy of aspirin for improving histology and preventing adverse outcomes in MASLD,” he said at the annual meeting of the American Association for the Study of Liver Diseases.

“We don’t have current plans, to my knowledge, to test full-dose aspirin,” he said in an interview. “I’m encouraged by the results with low-dose aspirin, and I think that, given the risk profile, using a lower dose is preferable.”
 

Reduction in inflammation

Although promising therapies for MASLD are in development, none are currently approved by the Food and Drug Administration, prompting Dr. Wilechansky and colleagues to investigate aspirin, with its anti-inflammatory properties, as a potential treatment.

In preclinical studies, aspirin has been shown to have both anti-inflammatory and antitumor effects in the liver through inhibition of cycloxygenase-2 and platelet-derived growth factor signaling, as well as through modulation of bioactive lipids, Dr. Wilechansky said.

In observational studies, use of aspirin was associated with a reduction in the prevalence of hepatic steatosis and fibrosis progression in patients with MASLD, and there was a decrease in the incidence of hepatocellular carcinoma and liver-related mortality among patients with viral hepatitis, he noted.

As for the potential mechanism of action of aspirin for patients with MASLD, Dr. Wilechansky noted that there may be some reduction in steatosis, and “if there is a reduction in inflammation, we may see some reduction in steatohepatitis.”
 

Study details

To see whether the so-called “wonder drug” could work wonders for patients with MASLD without cirrhosis, the researchers recruited 80 adults with MASLD and randomly assigned them to receive either aspirin 81 mg once daily or placebo for 6 months.

Patients with baseline cirrhosis or other liver disease, heavy drinkers, those who had used aspirin within 6 months, or those who used other antiplatelet or anticoagulant agents were excluded, as were patients with severe renal or cardiovascular disease, active cancer, pregnancy, were breastfeeding, had thrombocytopenia, or had undergone bariatric surgery within the past 2 years.

At baseline, 36.3% of all patients had F2-F3 fibrosis, as determined by vibration-controlled transient elastography (VCTE), and of 44 patients who had previously undergone liver biopsy, 37 (84.1%) were confirmed to have steatohepatitis.

At 6 months, the absolute change in hepatic fat fraction (HFF) from baseline, the primary endpoint, was a decline of 6.1% for patients taking aspirin, compared with a 4.2% increase for patients taking placebo, which translates into a 10.3% difference in favor of aspirin (P = .009).

The relative change in HFF, a secondary endpoint, for aspirin versus placebo was –59.2% (P = .003).

In addition, the use of aspirin was associated with a relative reduction in HFF of at least 30% among 16 of the 40 patients who received it.

Aspirin was significantly better than placebo for the secondary endpoints of absolute change in hepatic fat by MRI proton-density fat fraction, with –2.9% versus placebo (P = .018), and the relative change in hepatic fat by MRI-PDFF, with a difference of –24.8% versus placebo (P = .009).

Aspirin was also associated with significantly greater reductions in liver transaminase levels and liver stiffness by VCTE.

About one-third of patients in each study arm had at least one adverse event. There was only one aspirin-related adverse event (heartburn) that led to discontinuation. There were no serious bleeding events in either arm.

“We’re going to have to consider stratifying by aspirin use now in our trials,” said Mark Hartman, MD, from Eli Lilly in Indianapolis.
 

Significant weight gain in placebo group

Mary E. McCarthy Rinella, MD, FAASLD, professor of medicine at the University of Chicago, commented that the 4% increase in liver fat in the control arm “is kind of a lot for a placebo, and I’m wondering how much that accounts for the [difference] that you saw.” Dr. Rinella served as a comoderator of the session.

Dr. Wilechansky said that there were a few outliers in the placebo group who experienced significant weight gain during the study, including one patient who gained 15 kg over 6 months.

A post hoc analysis suggested that most of the increase in hepatic fat among patients who took placebo could have been among that handful of patients, he added. When those patients were removed in an adjusted analysis, the difference between the aspirin and placebo groups was smaller but remained significant.

The trial was sponsored by Massachusetts General Hospital. Dr. Wilechansky, Dr. Rinella, and Dr. Hartman had no relevant disclosures.

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

BOSTON – Patients with metabolic-associated steatotic liver disease (MASLD, formerly NAFLD) without cirrhosis who took daily low-dose aspirin in a double-blind randomized trial demonstrated significant reductions in liver fat content over 6 months compared with similar patients who took a placebo, study results show.

“In MASLD without cirrhosis, low-dose aspirin, 81 milligrams daily, led to decreases in liver fat and improved markers of hepatic inflammation and fibrosis,” reported Robert M. Wilechansky, MD, a transplant hepatology fellow at Massachusetts General Hospital in Boston.

“It was safe and well tolerated in this study, but we would like to see larger, longer-term clinical trials to test the efficacy of aspirin for improving histology and preventing adverse outcomes in MASLD,” he said at the annual meeting of the American Association for the Study of Liver Diseases.

“We don’t have current plans, to my knowledge, to test full-dose aspirin,” he said in an interview. “I’m encouraged by the results with low-dose aspirin, and I think that, given the risk profile, using a lower dose is preferable.”
 

Reduction in inflammation

Although promising therapies for MASLD are in development, none are currently approved by the Food and Drug Administration, prompting Dr. Wilechansky and colleagues to investigate aspirin, with its anti-inflammatory properties, as a potential treatment.

In preclinical studies, aspirin has been shown to have both anti-inflammatory and antitumor effects in the liver through inhibition of cycloxygenase-2 and platelet-derived growth factor signaling, as well as through modulation of bioactive lipids, Dr. Wilechansky said.

In observational studies, use of aspirin was associated with a reduction in the prevalence of hepatic steatosis and fibrosis progression in patients with MASLD, and there was a decrease in the incidence of hepatocellular carcinoma and liver-related mortality among patients with viral hepatitis, he noted.

As for the potential mechanism of action of aspirin for patients with MASLD, Dr. Wilechansky noted that there may be some reduction in steatosis, and “if there is a reduction in inflammation, we may see some reduction in steatohepatitis.”
 

Study details

To see whether the so-called “wonder drug” could work wonders for patients with MASLD without cirrhosis, the researchers recruited 80 adults with MASLD and randomly assigned them to receive either aspirin 81 mg once daily or placebo for 6 months.

Patients with baseline cirrhosis or other liver disease, heavy drinkers, those who had used aspirin within 6 months, or those who used other antiplatelet or anticoagulant agents were excluded, as were patients with severe renal or cardiovascular disease, active cancer, pregnancy, were breastfeeding, had thrombocytopenia, or had undergone bariatric surgery within the past 2 years.

At baseline, 36.3% of all patients had F2-F3 fibrosis, as determined by vibration-controlled transient elastography (VCTE), and of 44 patients who had previously undergone liver biopsy, 37 (84.1%) were confirmed to have steatohepatitis.

At 6 months, the absolute change in hepatic fat fraction (HFF) from baseline, the primary endpoint, was a decline of 6.1% for patients taking aspirin, compared with a 4.2% increase for patients taking placebo, which translates into a 10.3% difference in favor of aspirin (P = .009).

The relative change in HFF, a secondary endpoint, for aspirin versus placebo was –59.2% (P = .003).

In addition, the use of aspirin was associated with a relative reduction in HFF of at least 30% among 16 of the 40 patients who received it.

Aspirin was significantly better than placebo for the secondary endpoints of absolute change in hepatic fat by MRI proton-density fat fraction, with –2.9% versus placebo (P = .018), and the relative change in hepatic fat by MRI-PDFF, with a difference of –24.8% versus placebo (P = .009).

Aspirin was also associated with significantly greater reductions in liver transaminase levels and liver stiffness by VCTE.

About one-third of patients in each study arm had at least one adverse event. There was only one aspirin-related adverse event (heartburn) that led to discontinuation. There were no serious bleeding events in either arm.

“We’re going to have to consider stratifying by aspirin use now in our trials,” said Mark Hartman, MD, from Eli Lilly in Indianapolis.
 

Significant weight gain in placebo group

Mary E. McCarthy Rinella, MD, FAASLD, professor of medicine at the University of Chicago, commented that the 4% increase in liver fat in the control arm “is kind of a lot for a placebo, and I’m wondering how much that accounts for the [difference] that you saw.” Dr. Rinella served as a comoderator of the session.

Dr. Wilechansky said that there were a few outliers in the placebo group who experienced significant weight gain during the study, including one patient who gained 15 kg over 6 months.

A post hoc analysis suggested that most of the increase in hepatic fat among patients who took placebo could have been among that handful of patients, he added. When those patients were removed in an adjusted analysis, the difference between the aspirin and placebo groups was smaller but remained significant.

The trial was sponsored by Massachusetts General Hospital. Dr. Wilechansky, Dr. Rinella, and Dr. Hartman had no relevant disclosures.

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

BOSTON – Patients with metabolic-associated steatotic liver disease (MASLD, formerly NAFLD) without cirrhosis who took daily low-dose aspirin in a double-blind randomized trial demonstrated significant reductions in liver fat content over 6 months compared with similar patients who took a placebo, study results show.

“In MASLD without cirrhosis, low-dose aspirin, 81 milligrams daily, led to decreases in liver fat and improved markers of hepatic inflammation and fibrosis,” reported Robert M. Wilechansky, MD, a transplant hepatology fellow at Massachusetts General Hospital in Boston.

“It was safe and well tolerated in this study, but we would like to see larger, longer-term clinical trials to test the efficacy of aspirin for improving histology and preventing adverse outcomes in MASLD,” he said at the annual meeting of the American Association for the Study of Liver Diseases.

“We don’t have current plans, to my knowledge, to test full-dose aspirin,” he said in an interview. “I’m encouraged by the results with low-dose aspirin, and I think that, given the risk profile, using a lower dose is preferable.”
 

Reduction in inflammation

Although promising therapies for MASLD are in development, none are currently approved by the Food and Drug Administration, prompting Dr. Wilechansky and colleagues to investigate aspirin, with its anti-inflammatory properties, as a potential treatment.

In preclinical studies, aspirin has been shown to have both anti-inflammatory and antitumor effects in the liver through inhibition of cycloxygenase-2 and platelet-derived growth factor signaling, as well as through modulation of bioactive lipids, Dr. Wilechansky said.

In observational studies, use of aspirin was associated with a reduction in the prevalence of hepatic steatosis and fibrosis progression in patients with MASLD, and there was a decrease in the incidence of hepatocellular carcinoma and liver-related mortality among patients with viral hepatitis, he noted.

As for the potential mechanism of action of aspirin for patients with MASLD, Dr. Wilechansky noted that there may be some reduction in steatosis, and “if there is a reduction in inflammation, we may see some reduction in steatohepatitis.”
 

Study details

To see whether the so-called “wonder drug” could work wonders for patients with MASLD without cirrhosis, the researchers recruited 80 adults with MASLD and randomly assigned them to receive either aspirin 81 mg once daily or placebo for 6 months.

Patients with baseline cirrhosis or other liver disease, heavy drinkers, those who had used aspirin within 6 months, or those who used other antiplatelet or anticoagulant agents were excluded, as were patients with severe renal or cardiovascular disease, active cancer, pregnancy, were breastfeeding, had thrombocytopenia, or had undergone bariatric surgery within the past 2 years.

At baseline, 36.3% of all patients had F2-F3 fibrosis, as determined by vibration-controlled transient elastography (VCTE), and of 44 patients who had previously undergone liver biopsy, 37 (84.1%) were confirmed to have steatohepatitis.

At 6 months, the absolute change in hepatic fat fraction (HFF) from baseline, the primary endpoint, was a decline of 6.1% for patients taking aspirin, compared with a 4.2% increase for patients taking placebo, which translates into a 10.3% difference in favor of aspirin (P = .009).

The relative change in HFF, a secondary endpoint, for aspirin versus placebo was –59.2% (P = .003).

In addition, the use of aspirin was associated with a relative reduction in HFF of at least 30% among 16 of the 40 patients who received it.

Aspirin was significantly better than placebo for the secondary endpoints of absolute change in hepatic fat by MRI proton-density fat fraction, with –2.9% versus placebo (P = .018), and the relative change in hepatic fat by MRI-PDFF, with a difference of –24.8% versus placebo (P = .009).

Aspirin was also associated with significantly greater reductions in liver transaminase levels and liver stiffness by VCTE.

About one-third of patients in each study arm had at least one adverse event. There was only one aspirin-related adverse event (heartburn) that led to discontinuation. There were no serious bleeding events in either arm.

“We’re going to have to consider stratifying by aspirin use now in our trials,” said Mark Hartman, MD, from Eli Lilly in Indianapolis.
 

Significant weight gain in placebo group

Mary E. McCarthy Rinella, MD, FAASLD, professor of medicine at the University of Chicago, commented that the 4% increase in liver fat in the control arm “is kind of a lot for a placebo, and I’m wondering how much that accounts for the [difference] that you saw.” Dr. Rinella served as a comoderator of the session.

Dr. Wilechansky said that there were a few outliers in the placebo group who experienced significant weight gain during the study, including one patient who gained 15 kg over 6 months.

A post hoc analysis suggested that most of the increase in hepatic fat among patients who took placebo could have been among that handful of patients, he added. When those patients were removed in an adjusted analysis, the difference between the aspirin and placebo groups was smaller but remained significant.

The trial was sponsored by Massachusetts General Hospital. Dr. Wilechansky, Dr. Rinella, and Dr. Hartman had no relevant disclosures.

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

Sit less, move more. Or stand more. Or sleep more.

Replacing 30 minutes of sitting a day with equal time standing or even sleeping could improve obesity markers like body weight and waist circumference, according to a new cross-sectional study investigating the impact of movement behavior on cardiometabolic health. 

The findings suggest that, while higher-intensity activity may confer benefits sooner, adding more light activity or more standing, or even going to bed earlier, could improve heart health measures over time. 

“Our study highlights that replacing sedentary behavior with any other behavior can be beneficial,” said study author Joanna M. Blodgett, PhD, a researcher at University College London’s Institute of Sport, Exercise and Health, and department of targeted intervention.

The study builds on a large and growing body of evidence that movement behaviors impact cardiometabolic health. Increasing physical activity to 150 minutes a week has been shown to reduce the risk for cardiovascular disease by 17% and type 2 diabetes by 26%. Other studies suggest that even modest increases in physical activity can be beneficial. A prospective study published in October found that even short activity bouts of a few minutes a day may lower risks for heart attack, stroke, and early death. 

In the new study, researchers analyzed data from six studies and more than 15,000 participants, ranking behaviors according to their association with heart health. Moderate-to-vigorous activity was linked to the greatest benefit, followed by light activity, standing, sleeping, and finally – dead last on the list – sitting. 

A thigh-worn device tracked participants’ activity throughout the day, and six measures gauged heart health: body mass index (BMI), waist circumference, HDL cholesterol, total-cholesterol-to-HDL ratio, triglycerides, and glycated hemoglobin. 

Researchers modeled what would happen if people swapped various amounts of one activity for another every day for a week. Replacing just 4-13 minutes of sitting with moderate to vigorous activity improved heart health markers. 

The cardiovascular demands of regular intense activity like running, cycling, dancing, or playing sports – even in small bouts – strengthen the heart and improve blood flow throughout the body, Dr. Blodgett said. “This can lower cholesterol, blood pressure, and resting heart rate.”  

Even if adding moderate to vigorous activity is not an option, the findings suggest that people can still see benefits by replacing sitting with virtually any other activity – walking, standing, even sleeping.
 

Limitations

Because the study was observational, results can’t be used to infer causality.

“We cannot directly lean on the study results to guide prescriptions for particular exercise or lifestyle changes,” said Matthew Tomey, MD, a cardiologist with the Mount Sinai Health System, New York, who was not involved with the study. An interventional trial would be needed to confirm the findings.

The finding that sleep was better for participants than sitting is a good example. The benefits of replacing sitting with sleep were “clear” for adiposity measures like BMI and waist circumference, but negligible for blood markers such as cholesterol, triglycerides, and blood glucose, Dr. Blodgett said. 

One explanation: “The negative impact of sitting on these obesity measures is likely due to related unhealthy behaviors like snacking rather than the physiological benefits of sleep itself,” Dr. Blodgett said.

What’s more, study participants were relatively young, healthy, and active. The average age was 54, and they averaged nearly 8 hours of sleep, 10 hours of sitting, 3 hours of standing, 1.5 hours of light activity, and more than an hour of moderate to vigorous activity per day. So it’s difficult to draw conclusions about patients who don’t fit those metrics.
 

Impact on patient care

That said, the results could help tailor recommendations for patients, Dr. Blodgett said.

If a patient is struggling to exercise or is unable to exercise because of health or ability restrictions, you could help them find ways to add a lighter activity to their day, such as taking the stairs or walking briskly to catch the bus. Even swapping a regular desk for a standing one, or going to bed 30 minutes earlier, could be a more practical and effective suggestion. 

More than that: The research could be used to educate patients on the power of small changes. It shows that shifting daily habits even in small ways can make a difference, and people who are the least active stand to benefit the most. 

You can also remind patients that moderate or vigorous activity doesn’t need to happen at the gym. It could be lawn work, taking a walk, or moving heavy boxes. In fact, many activities can be “moderate” or even “vigorous” depending on the effort put into them. 

Share this rule of thumb: “An activity is classified as moderate intensity if you can talk but not sing while doing it, and an activity is generally considered vigorous intensity if you can’t say more than a few words without stopping to breathe,” Dr. Blodgett said.

The study also has implications for the potential of wearable activity trackers to monitor progress. Combining objective activity data with results from studies like this, and longer prospective studies, could help inform more helpful advice. 

“Ultimately, this research helps move us closer to more personalized guidance of how changing behaviors can improve your health,” Dr. Blodgett said.

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

Sit less, move more. Or stand more. Or sleep more.

Replacing 30 minutes of sitting a day with equal time standing or even sleeping could improve obesity markers like body weight and waist circumference, according to a new cross-sectional study investigating the impact of movement behavior on cardiometabolic health. 

The findings suggest that, while higher-intensity activity may confer benefits sooner, adding more light activity or more standing, or even going to bed earlier, could improve heart health measures over time. 

“Our study highlights that replacing sedentary behavior with any other behavior can be beneficial,” said study author Joanna M. Blodgett, PhD, a researcher at University College London’s Institute of Sport, Exercise and Health, and department of targeted intervention.

The study builds on a large and growing body of evidence that movement behaviors impact cardiometabolic health. Increasing physical activity to 150 minutes a week has been shown to reduce the risk for cardiovascular disease by 17% and type 2 diabetes by 26%. Other studies suggest that even modest increases in physical activity can be beneficial. A prospective study published in October found that even short activity bouts of a few minutes a day may lower risks for heart attack, stroke, and early death. 

In the new study, researchers analyzed data from six studies and more than 15,000 participants, ranking behaviors according to their association with heart health. Moderate-to-vigorous activity was linked to the greatest benefit, followed by light activity, standing, sleeping, and finally – dead last on the list – sitting. 

A thigh-worn device tracked participants’ activity throughout the day, and six measures gauged heart health: body mass index (BMI), waist circumference, HDL cholesterol, total-cholesterol-to-HDL ratio, triglycerides, and glycated hemoglobin. 

Researchers modeled what would happen if people swapped various amounts of one activity for another every day for a week. Replacing just 4-13 minutes of sitting with moderate to vigorous activity improved heart health markers. 

The cardiovascular demands of regular intense activity like running, cycling, dancing, or playing sports – even in small bouts – strengthen the heart and improve blood flow throughout the body, Dr. Blodgett said. “This can lower cholesterol, blood pressure, and resting heart rate.”  

Even if adding moderate to vigorous activity is not an option, the findings suggest that people can still see benefits by replacing sitting with virtually any other activity – walking, standing, even sleeping.
 

Limitations

Because the study was observational, results can’t be used to infer causality.

“We cannot directly lean on the study results to guide prescriptions for particular exercise or lifestyle changes,” said Matthew Tomey, MD, a cardiologist with the Mount Sinai Health System, New York, who was not involved with the study. An interventional trial would be needed to confirm the findings.

The finding that sleep was better for participants than sitting is a good example. The benefits of replacing sitting with sleep were “clear” for adiposity measures like BMI and waist circumference, but negligible for blood markers such as cholesterol, triglycerides, and blood glucose, Dr. Blodgett said. 

One explanation: “The negative impact of sitting on these obesity measures is likely due to related unhealthy behaviors like snacking rather than the physiological benefits of sleep itself,” Dr. Blodgett said.

What’s more, study participants were relatively young, healthy, and active. The average age was 54, and they averaged nearly 8 hours of sleep, 10 hours of sitting, 3 hours of standing, 1.5 hours of light activity, and more than an hour of moderate to vigorous activity per day. So it’s difficult to draw conclusions about patients who don’t fit those metrics.
 

Impact on patient care

That said, the results could help tailor recommendations for patients, Dr. Blodgett said.

If a patient is struggling to exercise or is unable to exercise because of health or ability restrictions, you could help them find ways to add a lighter activity to their day, such as taking the stairs or walking briskly to catch the bus. Even swapping a regular desk for a standing one, or going to bed 30 minutes earlier, could be a more practical and effective suggestion. 

More than that: The research could be used to educate patients on the power of small changes. It shows that shifting daily habits even in small ways can make a difference, and people who are the least active stand to benefit the most. 

You can also remind patients that moderate or vigorous activity doesn’t need to happen at the gym. It could be lawn work, taking a walk, or moving heavy boxes. In fact, many activities can be “moderate” or even “vigorous” depending on the effort put into them. 

Share this rule of thumb: “An activity is classified as moderate intensity if you can talk but not sing while doing it, and an activity is generally considered vigorous intensity if you can’t say more than a few words without stopping to breathe,” Dr. Blodgett said.

The study also has implications for the potential of wearable activity trackers to monitor progress. Combining objective activity data with results from studies like this, and longer prospective studies, could help inform more helpful advice. 

“Ultimately, this research helps move us closer to more personalized guidance of how changing behaviors can improve your health,” Dr. Blodgett said.

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

Sit less, move more. Or stand more. Or sleep more.

Replacing 30 minutes of sitting a day with equal time standing or even sleeping could improve obesity markers like body weight and waist circumference, according to a new cross-sectional study investigating the impact of movement behavior on cardiometabolic health. 

The findings suggest that, while higher-intensity activity may confer benefits sooner, adding more light activity or more standing, or even going to bed earlier, could improve heart health measures over time. 

“Our study highlights that replacing sedentary behavior with any other behavior can be beneficial,” said study author Joanna M. Blodgett, PhD, a researcher at University College London’s Institute of Sport, Exercise and Health, and department of targeted intervention.

The study builds on a large and growing body of evidence that movement behaviors impact cardiometabolic health. Increasing physical activity to 150 minutes a week has been shown to reduce the risk for cardiovascular disease by 17% and type 2 diabetes by 26%. Other studies suggest that even modest increases in physical activity can be beneficial. A prospective study published in October found that even short activity bouts of a few minutes a day may lower risks for heart attack, stroke, and early death. 

In the new study, researchers analyzed data from six studies and more than 15,000 participants, ranking behaviors according to their association with heart health. Moderate-to-vigorous activity was linked to the greatest benefit, followed by light activity, standing, sleeping, and finally – dead last on the list – sitting. 

A thigh-worn device tracked participants’ activity throughout the day, and six measures gauged heart health: body mass index (BMI), waist circumference, HDL cholesterol, total-cholesterol-to-HDL ratio, triglycerides, and glycated hemoglobin. 

Researchers modeled what would happen if people swapped various amounts of one activity for another every day for a week. Replacing just 4-13 minutes of sitting with moderate to vigorous activity improved heart health markers. 

The cardiovascular demands of regular intense activity like running, cycling, dancing, or playing sports – even in small bouts – strengthen the heart and improve blood flow throughout the body, Dr. Blodgett said. “This can lower cholesterol, blood pressure, and resting heart rate.”  

Even if adding moderate to vigorous activity is not an option, the findings suggest that people can still see benefits by replacing sitting with virtually any other activity – walking, standing, even sleeping.
 

Limitations

Because the study was observational, results can’t be used to infer causality.

“We cannot directly lean on the study results to guide prescriptions for particular exercise or lifestyle changes,” said Matthew Tomey, MD, a cardiologist with the Mount Sinai Health System, New York, who was not involved with the study. An interventional trial would be needed to confirm the findings.

The finding that sleep was better for participants than sitting is a good example. The benefits of replacing sitting with sleep were “clear” for adiposity measures like BMI and waist circumference, but negligible for blood markers such as cholesterol, triglycerides, and blood glucose, Dr. Blodgett said. 

One explanation: “The negative impact of sitting on these obesity measures is likely due to related unhealthy behaviors like snacking rather than the physiological benefits of sleep itself,” Dr. Blodgett said.

What’s more, study participants were relatively young, healthy, and active. The average age was 54, and they averaged nearly 8 hours of sleep, 10 hours of sitting, 3 hours of standing, 1.5 hours of light activity, and more than an hour of moderate to vigorous activity per day. So it’s difficult to draw conclusions about patients who don’t fit those metrics.
 

Impact on patient care

That said, the results could help tailor recommendations for patients, Dr. Blodgett said.

If a patient is struggling to exercise or is unable to exercise because of health or ability restrictions, you could help them find ways to add a lighter activity to their day, such as taking the stairs or walking briskly to catch the bus. Even swapping a regular desk for a standing one, or going to bed 30 minutes earlier, could be a more practical and effective suggestion. 

More than that: The research could be used to educate patients on the power of small changes. It shows that shifting daily habits even in small ways can make a difference, and people who are the least active stand to benefit the most. 

You can also remind patients that moderate or vigorous activity doesn’t need to happen at the gym. It could be lawn work, taking a walk, or moving heavy boxes. In fact, many activities can be “moderate” or even “vigorous” depending on the effort put into them. 

Share this rule of thumb: “An activity is classified as moderate intensity if you can talk but not sing while doing it, and an activity is generally considered vigorous intensity if you can’t say more than a few words without stopping to breathe,” Dr. Blodgett said.

The study also has implications for the potential of wearable activity trackers to monitor progress. Combining objective activity data with results from studies like this, and longer prospective studies, could help inform more helpful advice. 

“Ultimately, this research helps move us closer to more personalized guidance of how changing behaviors can improve your health,” Dr. Blodgett said.

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

Those who embrace lifestyle medicine are familiar with the slogan Dean Ornish, MD, likes to use: Eat well, move more, stress less, love more.

That last one, love, was the renowned physician and author’s focus at the recent American College of Lifestyle Medicine Conference in Denver. That’s because love – essentially the support, connectedness, and caring that patients feel when they join a lifestyle-change program – is “where healing occurs at the deepest level.”

Indeed, social connectedness is emerging as a vital pillar in the burgeoning field of lifestyle medicine, a specialty that uses lifestyle interventions to treat chronic conditions. About 300 lifestyle medicine programs are now integrated into residencies in medical schools across the country, up from a handful just 5 years ago, said Meagan Grega, MD, the conference chair.

“The energy and growth in American lifestyle medicine is unparalleled by anything else I see in the health care world right now,” said Dr. Grega, a family physician for 25 years in eastern Pennsylvania.

The field applies volumes of research, from the 1990s to today, demonstrating the healing effects of lifestyle changes. Dr. Ornish’s Preventive Medicine Research Institute has published research on small changes (like pomegranate juice helping blood flow in the heart) and huge ones: Coronary heart patients reversed the narrowing of arteries without lipid-lowering drugs after 1 year of lifestyle changes, including a vegetarian diet, aerobic exercise, stress management, and group support.

Ranking alongside bedrocks such as healthy diet, sleep, exercise, and stress management is positive social connection. That part, the “love more” part, often draws skepticism but is vital, said Dr. Ornish, who is sometimes referred to as the father of lifestyle medicine.

It’s “invariably the part that’s the most meaningful – that sense of connection to community that can come when you bring total strangers together,” Dr. Ornish said. “The ‘love more’ part, in many ways, is not only as important, but in some ways even more because everything really flows from that.”

Patients in a support group, who can “let down their emotional defenses and talk openly and authentically,” are much more likely to make and maintain healthy changes, Dr. Ornish said.
 

Love as medicine

The healing power of love may sound like pseudoscience, but more and more research backs the health benefits of connection and the hazards of isolation.

Mounting evidence links loneliness and isolation with a range of health issues, from mood disorders such as depression to chronic conditions such as cardiovascular disease. What’s more, data suggest that loneliness and social isolation in the United States are on the rise, and the COVID pandemic made that more clear. In May 2023, Surgeon General Vivek Murthy, MD, called loneliness, isolation, and lack of connection in the United States a “public health crisis.”

“Good relationships keep us happier and healthier,” said Robert Waldinger, MD, a psychiatrist at Massachusetts General Hospital, Boston.

Dr. Waldinger, who was not affiliated with the conference, is head of the Harvard Study of Adult Development, one of the longest studies of adult life. Beginning in 1938, the study has tracked 724 people plus more than 1,300 of their descendants and found that embracing community and close relationships helps us live longer and be happier.

In the study, the people who were most satisfied with their relationships at age 50 years were the healthiest at age 80 years. Knowing you have someone to rely on protects the brain: “Those people’s memories stay sharper longer,” Dr. Waldinger said.

He draws a distinction between connection and love. “Love is, I think, more of a feeling,” Dr. Waldinger noted. “Connection is a feeling, but it’s also an activity.”

One in five Americans say they’re lonely, he said, “and loneliness is a stressor.” People who are isolated don’t sleep as well, he added. Their health declines earlier in midlife, brain function slips sooner, and their lives are shorter.

“You don’t have anyone to complain to,” he said. If you do, “you can feel your body start to calm down.” Those without social connections may stay in a low-level “fight-or-flight mode.”

“What we think happens is that you have low levels of inflammation chronically, and those can gradually break down body systems.” Moreover, higher rates of cardiac reactivity, for instance, a racing heartbeat when upset, can lead to high blood pressure and lower immune function.

In his talk, Dr. Ornish said, “Anger is that one emotion that has consistently been shown to make heart disease worse.”

Helping people in those straits is gratifying, Dr. Ornish said. “If we can work with people as lifestyle medicine practitioners when they’re suffering, there’s an opportunity for transformation.”
 

Future

Of course, that can be easier said than done. Dr. Ornish relayed a patient’s typical reaction to a lifestyle program: “This is kind of weird stuff. Like, I get diet. But a plant-based diet, really? Meditation? Loving more? Really?”

He told the conference, “Part of our job as lifestyle medicine practitioners is to spend a little extra time with them. It doesn’t even take that much time. And to really help them understand what brings them a sense of hope and meaning and purpose.”

The results can be motivating. “Most people feel so much better so quickly,” Dr. Ornish said. “It reframes the reason for change from fear of dying to joy of living.”

Dr. Grega, for one, is optimistic for the future, citing survey results showing that 95% of medical students think that they›d be better counselors with lifestyle training. ‘They passionately want this type of thing,” she said.

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

Those who embrace lifestyle medicine are familiar with the slogan Dean Ornish, MD, likes to use: Eat well, move more, stress less, love more.

That last one, love, was the renowned physician and author’s focus at the recent American College of Lifestyle Medicine Conference in Denver. That’s because love – essentially the support, connectedness, and caring that patients feel when they join a lifestyle-change program – is “where healing occurs at the deepest level.”

Indeed, social connectedness is emerging as a vital pillar in the burgeoning field of lifestyle medicine, a specialty that uses lifestyle interventions to treat chronic conditions. About 300 lifestyle medicine programs are now integrated into residencies in medical schools across the country, up from a handful just 5 years ago, said Meagan Grega, MD, the conference chair.

“The energy and growth in American lifestyle medicine is unparalleled by anything else I see in the health care world right now,” said Dr. Grega, a family physician for 25 years in eastern Pennsylvania.

The field applies volumes of research, from the 1990s to today, demonstrating the healing effects of lifestyle changes. Dr. Ornish’s Preventive Medicine Research Institute has published research on small changes (like pomegranate juice helping blood flow in the heart) and huge ones: Coronary heart patients reversed the narrowing of arteries without lipid-lowering drugs after 1 year of lifestyle changes, including a vegetarian diet, aerobic exercise, stress management, and group support.

Ranking alongside bedrocks such as healthy diet, sleep, exercise, and stress management is positive social connection. That part, the “love more” part, often draws skepticism but is vital, said Dr. Ornish, who is sometimes referred to as the father of lifestyle medicine.

It’s “invariably the part that’s the most meaningful – that sense of connection to community that can come when you bring total strangers together,” Dr. Ornish said. “The ‘love more’ part, in many ways, is not only as important, but in some ways even more because everything really flows from that.”

Patients in a support group, who can “let down their emotional defenses and talk openly and authentically,” are much more likely to make and maintain healthy changes, Dr. Ornish said.
 

Love as medicine

The healing power of love may sound like pseudoscience, but more and more research backs the health benefits of connection and the hazards of isolation.

Mounting evidence links loneliness and isolation with a range of health issues, from mood disorders such as depression to chronic conditions such as cardiovascular disease. What’s more, data suggest that loneliness and social isolation in the United States are on the rise, and the COVID pandemic made that more clear. In May 2023, Surgeon General Vivek Murthy, MD, called loneliness, isolation, and lack of connection in the United States a “public health crisis.”

“Good relationships keep us happier and healthier,” said Robert Waldinger, MD, a psychiatrist at Massachusetts General Hospital, Boston.

Dr. Waldinger, who was not affiliated with the conference, is head of the Harvard Study of Adult Development, one of the longest studies of adult life. Beginning in 1938, the study has tracked 724 people plus more than 1,300 of their descendants and found that embracing community and close relationships helps us live longer and be happier.

In the study, the people who were most satisfied with their relationships at age 50 years were the healthiest at age 80 years. Knowing you have someone to rely on protects the brain: “Those people’s memories stay sharper longer,” Dr. Waldinger said.

He draws a distinction between connection and love. “Love is, I think, more of a feeling,” Dr. Waldinger noted. “Connection is a feeling, but it’s also an activity.”

One in five Americans say they’re lonely, he said, “and loneliness is a stressor.” People who are isolated don’t sleep as well, he added. Their health declines earlier in midlife, brain function slips sooner, and their lives are shorter.

“You don’t have anyone to complain to,” he said. If you do, “you can feel your body start to calm down.” Those without social connections may stay in a low-level “fight-or-flight mode.”

“What we think happens is that you have low levels of inflammation chronically, and those can gradually break down body systems.” Moreover, higher rates of cardiac reactivity, for instance, a racing heartbeat when upset, can lead to high blood pressure and lower immune function.

In his talk, Dr. Ornish said, “Anger is that one emotion that has consistently been shown to make heart disease worse.”

Helping people in those straits is gratifying, Dr. Ornish said. “If we can work with people as lifestyle medicine practitioners when they’re suffering, there’s an opportunity for transformation.”
 

Future

Of course, that can be easier said than done. Dr. Ornish relayed a patient’s typical reaction to a lifestyle program: “This is kind of weird stuff. Like, I get diet. But a plant-based diet, really? Meditation? Loving more? Really?”

He told the conference, “Part of our job as lifestyle medicine practitioners is to spend a little extra time with them. It doesn’t even take that much time. And to really help them understand what brings them a sense of hope and meaning and purpose.”

The results can be motivating. “Most people feel so much better so quickly,” Dr. Ornish said. “It reframes the reason for change from fear of dying to joy of living.”

Dr. Grega, for one, is optimistic for the future, citing survey results showing that 95% of medical students think that they›d be better counselors with lifestyle training. ‘They passionately want this type of thing,” she said.

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

Those who embrace lifestyle medicine are familiar with the slogan Dean Ornish, MD, likes to use: Eat well, move more, stress less, love more.

That last one, love, was the renowned physician and author’s focus at the recent American College of Lifestyle Medicine Conference in Denver. That’s because love – essentially the support, connectedness, and caring that patients feel when they join a lifestyle-change program – is “where healing occurs at the deepest level.”

Indeed, social connectedness is emerging as a vital pillar in the burgeoning field of lifestyle medicine, a specialty that uses lifestyle interventions to treat chronic conditions. About 300 lifestyle medicine programs are now integrated into residencies in medical schools across the country, up from a handful just 5 years ago, said Meagan Grega, MD, the conference chair.

“The energy and growth in American lifestyle medicine is unparalleled by anything else I see in the health care world right now,” said Dr. Grega, a family physician for 25 years in eastern Pennsylvania.

The field applies volumes of research, from the 1990s to today, demonstrating the healing effects of lifestyle changes. Dr. Ornish’s Preventive Medicine Research Institute has published research on small changes (like pomegranate juice helping blood flow in the heart) and huge ones: Coronary heart patients reversed the narrowing of arteries without lipid-lowering drugs after 1 year of lifestyle changes, including a vegetarian diet, aerobic exercise, stress management, and group support.

Ranking alongside bedrocks such as healthy diet, sleep, exercise, and stress management is positive social connection. That part, the “love more” part, often draws skepticism but is vital, said Dr. Ornish, who is sometimes referred to as the father of lifestyle medicine.

It’s “invariably the part that’s the most meaningful – that sense of connection to community that can come when you bring total strangers together,” Dr. Ornish said. “The ‘love more’ part, in many ways, is not only as important, but in some ways even more because everything really flows from that.”

Patients in a support group, who can “let down their emotional defenses and talk openly and authentically,” are much more likely to make and maintain healthy changes, Dr. Ornish said.
 

Love as medicine

The healing power of love may sound like pseudoscience, but more and more research backs the health benefits of connection and the hazards of isolation.

Mounting evidence links loneliness and isolation with a range of health issues, from mood disorders such as depression to chronic conditions such as cardiovascular disease. What’s more, data suggest that loneliness and social isolation in the United States are on the rise, and the COVID pandemic made that more clear. In May 2023, Surgeon General Vivek Murthy, MD, called loneliness, isolation, and lack of connection in the United States a “public health crisis.”

“Good relationships keep us happier and healthier,” said Robert Waldinger, MD, a psychiatrist at Massachusetts General Hospital, Boston.

Dr. Waldinger, who was not affiliated with the conference, is head of the Harvard Study of Adult Development, one of the longest studies of adult life. Beginning in 1938, the study has tracked 724 people plus more than 1,300 of their descendants and found that embracing community and close relationships helps us live longer and be happier.

In the study, the people who were most satisfied with their relationships at age 50 years were the healthiest at age 80 years. Knowing you have someone to rely on protects the brain: “Those people’s memories stay sharper longer,” Dr. Waldinger said.

He draws a distinction between connection and love. “Love is, I think, more of a feeling,” Dr. Waldinger noted. “Connection is a feeling, but it’s also an activity.”

One in five Americans say they’re lonely, he said, “and loneliness is a stressor.” People who are isolated don’t sleep as well, he added. Their health declines earlier in midlife, brain function slips sooner, and their lives are shorter.

“You don’t have anyone to complain to,” he said. If you do, “you can feel your body start to calm down.” Those without social connections may stay in a low-level “fight-or-flight mode.”

“What we think happens is that you have low levels of inflammation chronically, and those can gradually break down body systems.” Moreover, higher rates of cardiac reactivity, for instance, a racing heartbeat when upset, can lead to high blood pressure and lower immune function.

In his talk, Dr. Ornish said, “Anger is that one emotion that has consistently been shown to make heart disease worse.”

Helping people in those straits is gratifying, Dr. Ornish said. “If we can work with people as lifestyle medicine practitioners when they’re suffering, there’s an opportunity for transformation.”
 

Future

Of course, that can be easier said than done. Dr. Ornish relayed a patient’s typical reaction to a lifestyle program: “This is kind of weird stuff. Like, I get diet. But a plant-based diet, really? Meditation? Loving more? Really?”

He told the conference, “Part of our job as lifestyle medicine practitioners is to spend a little extra time with them. It doesn’t even take that much time. And to really help them understand what brings them a sense of hope and meaning and purpose.”

The results can be motivating. “Most people feel so much better so quickly,” Dr. Ornish said. “It reframes the reason for change from fear of dying to joy of living.”

Dr. Grega, for one, is optimistic for the future, citing survey results showing that 95% of medical students think that they›d be better counselors with lifestyle training. ‘They passionately want this type of thing,” she said.

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