Diabetes Hub

TOPLINE:

A triple combination therapy (TCT) of metformin, dapagliflozin, and saxagliptin is an effective and safe treatment option for drug-naive patients with type 2 diabetes (T2D) compared with stepwise add-on therapy.

METHODOLOGY:

• Current guidelines recommend early combination therapy to extend the time to treatment failure, reduce the risk for diabetic complications, and prevent clinical inertia in patients with T2D.
• This randomized controlled open-label trial conducted at nine sites in South Korea included 105 drug-naive patients with T2D (mean age, 49.5 years; 32.4% women) who either received triple therapy (metformin, dapagliflozin, and saxagliptin) or stepwise add-on therapy (initiated with metformin, followed by glimepiride and sitagliptin for those with baseline hemoglobin A1c levels < 9.0% or with initial dual metformin and glimepiride in those with A1c levels ≥ 9.0% followed by sitagliptin).
• The primary outcome was the proportion of patients who achieved A1c levels < 6.5% without hypoglycemia, weight gain ≥ 5%, or discontinuation of drugs because of adverse events at week 104.
• The secondary outcomes were the proportion of patients whose A1c levels dropped to < 7.0% at weeks 56 and 104 and dropped to < 6.5% at week 56, all without hypoglycemia, weight gain, nor discontinuation due to adverse events.

TAKEAWAY:

• At week 104, a higher proportion of patients in the triple therapy group achieved the primary outcome than those in the stepwise add-on therapy group (39.0% vs 17.1%; P = .027).
• In both groups, a similar proportion of patients (46.3%) achieved A1c levels < 6.5% at week 104, but the proportion of patients without hypoglycemia, weight gain, or discontinuation because of adverse events was higher in the triple therapy group than those in the stepwise add-on therapy group (83.3% vs 38.0%; P < .001).

IN PRACTICE:

The authors wrote: “Although the glycemic efficacy of each drug in the TCT was modest, the combination of these drugs resulted in a 2-year durable glycemic efficacy, with greater than a 2.5% reduction in A1c levels from baseline. The overall results of this study suggest a novel strategy for initial combination therapy in newly diagnosed T2D patients.”

SOURCE:

The study was led by Nam Hoon Kim, MD, of the Department of Internal Medicine, Korea University College of Medicine, Seoul. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study had a relatively small sample size as compared with previous clinical trials. More people in the standard therapy group had A1c levels ≥ 9.0%, which resulted in more than double the number of people receiving dual combination therapy over monotherapy in that group. The trial duration was insufficient to evaluate the cardiovascular outcomes.

DISCLOSURES:

The study was funded by AstraZeneca. Some authors reported financial ties with AstraZeneca and other pharmaceutical and medical device companies as members of advisory boards or recipients of grants, consulting fees, honoraria, or lecture fees.

A version of this article appeared on Medscape.com.

TOPLINE:

A triple combination therapy (TCT) of metformin, dapagliflozin, and saxagliptin is an effective and safe treatment option for drug-naive patients with type 2 diabetes (T2D) compared with stepwise add-on therapy.

METHODOLOGY:

• Current guidelines recommend early combination therapy to extend the time to treatment failure, reduce the risk for diabetic complications, and prevent clinical inertia in patients with T2D.
• This randomized controlled open-label trial conducted at nine sites in South Korea included 105 drug-naive patients with T2D (mean age, 49.5 years; 32.4% women) who either received triple therapy (metformin, dapagliflozin, and saxagliptin) or stepwise add-on therapy (initiated with metformin, followed by glimepiride and sitagliptin for those with baseline hemoglobin A1c levels < 9.0% or with initial dual metformin and glimepiride in those with A1c levels ≥ 9.0% followed by sitagliptin).
• The primary outcome was the proportion of patients who achieved A1c levels < 6.5% without hypoglycemia, weight gain ≥ 5%, or discontinuation of drugs because of adverse events at week 104.
• The secondary outcomes were the proportion of patients whose A1c levels dropped to < 7.0% at weeks 56 and 104 and dropped to < 6.5% at week 56, all without hypoglycemia, weight gain, nor discontinuation due to adverse events.

TAKEAWAY:

• At week 104, a higher proportion of patients in the triple therapy group achieved the primary outcome than those in the stepwise add-on therapy group (39.0% vs 17.1%; P = .027).
• In both groups, a similar proportion of patients (46.3%) achieved A1c levels < 6.5% at week 104, but the proportion of patients without hypoglycemia, weight gain, or discontinuation because of adverse events was higher in the triple therapy group than those in the stepwise add-on therapy group (83.3% vs 38.0%; P < .001).

IN PRACTICE:

The authors wrote: “Although the glycemic efficacy of each drug in the TCT was modest, the combination of these drugs resulted in a 2-year durable glycemic efficacy, with greater than a 2.5% reduction in A1c levels from baseline. The overall results of this study suggest a novel strategy for initial combination therapy in newly diagnosed T2D patients.”

SOURCE:

The study was led by Nam Hoon Kim, MD, of the Department of Internal Medicine, Korea University College of Medicine, Seoul. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study had a relatively small sample size as compared with previous clinical trials. More people in the standard therapy group had A1c levels ≥ 9.0%, which resulted in more than double the number of people receiving dual combination therapy over monotherapy in that group. The trial duration was insufficient to evaluate the cardiovascular outcomes.

DISCLOSURES:

The study was funded by AstraZeneca. Some authors reported financial ties with AstraZeneca and other pharmaceutical and medical device companies as members of advisory boards or recipients of grants, consulting fees, honoraria, or lecture fees.

A version of this article appeared on Medscape.com.

TOPLINE:

A triple combination therapy (TCT) of metformin, dapagliflozin, and saxagliptin is an effective and safe treatment option for drug-naive patients with type 2 diabetes (T2D) compared with stepwise add-on therapy.

METHODOLOGY:

• Current guidelines recommend early combination therapy to extend the time to treatment failure, reduce the risk for diabetic complications, and prevent clinical inertia in patients with T2D.
• This randomized controlled open-label trial conducted at nine sites in South Korea included 105 drug-naive patients with T2D (mean age, 49.5 years; 32.4% women) who either received triple therapy (metformin, dapagliflozin, and saxagliptin) or stepwise add-on therapy (initiated with metformin, followed by glimepiride and sitagliptin for those with baseline hemoglobin A1c levels < 9.0% or with initial dual metformin and glimepiride in those with A1c levels ≥ 9.0% followed by sitagliptin).
• The primary outcome was the proportion of patients who achieved A1c levels < 6.5% without hypoglycemia, weight gain ≥ 5%, or discontinuation of drugs because of adverse events at week 104.
• The secondary outcomes were the proportion of patients whose A1c levels dropped to < 7.0% at weeks 56 and 104 and dropped to < 6.5% at week 56, all without hypoglycemia, weight gain, nor discontinuation due to adverse events.

TAKEAWAY:

• At week 104, a higher proportion of patients in the triple therapy group achieved the primary outcome than those in the stepwise add-on therapy group (39.0% vs 17.1%; P = .027).
• In both groups, a similar proportion of patients (46.3%) achieved A1c levels < 6.5% at week 104, but the proportion of patients without hypoglycemia, weight gain, or discontinuation because of adverse events was higher in the triple therapy group than those in the stepwise add-on therapy group (83.3% vs 38.0%; P < .001).

IN PRACTICE:

The authors wrote: “Although the glycemic efficacy of each drug in the TCT was modest, the combination of these drugs resulted in a 2-year durable glycemic efficacy, with greater than a 2.5% reduction in A1c levels from baseline. The overall results of this study suggest a novel strategy for initial combination therapy in newly diagnosed T2D patients.”

SOURCE:

The study was led by Nam Hoon Kim, MD, of the Department of Internal Medicine, Korea University College of Medicine, Seoul. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study had a relatively small sample size as compared with previous clinical trials. More people in the standard therapy group had A1c levels ≥ 9.0%, which resulted in more than double the number of people receiving dual combination therapy over monotherapy in that group. The trial duration was insufficient to evaluate the cardiovascular outcomes.

DISCLOSURES:

The study was funded by AstraZeneca. Some authors reported financial ties with AstraZeneca and other pharmaceutical and medical device companies as members of advisory boards or recipients of grants, consulting fees, honoraria, or lecture fees.

A version of this article appeared on Medscape.com.

It seems intuitive that, because people with type 2 diabetes (T2D) generally need to avoid sugar, clinicians should recommend eating foods and using recipes containing artificial sweeteners such as sucralose instead.

Splenda, which produces sucralose and other non-sugar sweeteners (NSS), is a sponsor of the American Diabetes Association (ADA) Diabetes Food Hub. Earlier in 2024, the ADA settled a lawsuit regarding its former director of nutrition’s refusal to approve recipes containing sucralose (Splenda), which she believed “flew in the face of the ADA’s mission.” 

Experts agree that, while artificial sweeteners may help in certain scenarios, they can also be harmful.

“There’s not a lot of evidence that sweeteners like sucralose provide significant benefits, especially over the long term,” said Susan Swithers, PhD, professor, department of psychological sciences and associate dean for faculty affairs at Purdue University, West Lafayette, Indiana.

Dr. Swithers authored an article several years ago cautioning that consuming nonnutritive sweeteners in beverages not only fails to prevent disease but also is associated with an increase in risks for the same health outcomes associated with sugar-sweetened beverages, including T2D, cardiovascular disease, hypertension, and stroke.

“At this point, we have pretty good evidence that these chemicals that were once touted as being completely inert are, in fact, not inert,” she said. “We know that they’re unlikely to be toxic in the short term, but they are not benign, and they have consequences. Right now, we have little understanding of the outcomes of consumption of these products chronically.”
 

What the Science Says

In 2023, the World Health Organization (WHO) released a guideline on NSS that recommended against their use for weight control or to reduce the risk for noncommunicable diseases.

The systematic review and meta-analysis upon which the guideline is based found that high intakes of NSS were associated with increases in body mass index and, as Dr. Swithers found, risks of developing T2D, cardiovascular events, and any type of stroke, as well as hypertension, bladder cancer, and all-cause mortality.

In a press release announcing the guideline, Francesco Branca, WHO director for Nutrition and Food Safety, said, “NSS are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health.” 

The “common” NSS named by WHO included sucralose, as well as acesulfame K, aspartame, advantame, cyclamates, neotame, saccharin, stevia, and stevia derivatives.

If NSS consumption can increase T2D risk, what about people who already have T2D? 

Some research suggests that NSS may affect people with and without T2D differently, said Dr. Swithers. For example, one small study showed that sucralose enhanced glucagon-like peptide 1 release and lowered blood glucose in healthy patients but not in patients with newly diagnosed T2D.

Similarly, Jotham Suez, PhD, an assistant professor in the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, said in an interview that his group “showed for the first time in 2014 that disruption of the microbiome by artificial sweeteners is causally linked to disrupted glycemic control.” 

Recently, the team studied the impact of sucralose, aspartame, saccharin, and stevia in healthy adults and “were surprised to discover that all four sweeteners altered gut bacteria and the molecules they secrete,” he said. However, subsequent glucose tolerance tests in healthy humans showed varying results, “suggesting that human microbiome responses to the nonnutritive sweeteners we assessed are highly personalized and may lead to glycemic alterations in some, but not all, consumers depending on their microbes and the sweeteners they consume.” 

Nevertheless, a recent review led by researchers in Mexico concluded that sucralose consumption “is associated with various adverse health effects. Despite being considered safe following previous studies, recent research suggests possible links to systemic inflammation, metabolic diseases, disruptions in gut microbiota, liver damage, and toxic effects at the cellular level.” 

In addition, they wrote, “it is crucial to highlight the persistence of sucralose in the body, its ability to cross the placenta, and its presence in breast milk, raising concerns about prenatal and neonatal exposure.” 

Sabyasachi Sen, MD, a professor of biochemistry and molecular medicine at George Washington School of Medicine & Health Sciences, Washington, DC, has led and coauthored preclinical and clinical studies demonstrating the potential ill effects of sucralose and other artificial sweeteners. One showed that sucralose and acesulfame potassium–containing diet soda altered microbial taxa in two pilot studies in healthy young adults; another showed a connection between artificial sweeteners and inflammation.

But Dr. Sen’s current work is directed at his team’s finding that sucralose promotes the accumulation of reactive oxygen species and adipogenesis in human stem cells, he said in an interview. “It is essentially an additive that is clearly harmful to cells. Our concern is that stem cells are going to remain in the system for a long period of time. If it is causing inflammation in these cells, then that may lead to adverse outcomes.”

Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment & Education Center at Cedars-Sinai in Los Angeles, California, is the principal investigator of a recent study suggesting that non-aspartame NSS and aspartame alone may alter the structure and function of the stool and duodenal microbiomes. Levels of circulating inflammatory markers were also altered in participants who consumed artificial sweeteners, compared with control participants who did not.

In addition to these potential adverse effects, “we have to think about the fact that patients with diabetes often have other comorbidities like obesity and are at higher risk for cardiovascular disease and other conditions,” she said in an interview. “If you’re taking a patient who’s already at risk for those things and you don’t have a detailed discussion with them about pros and cons, you’re doing them a disservice.” 
 

Industry Interests

Addressing the largely negative but varying findings, Dr. Swithers said, “one of the difficulties with getting clear answers about the science is that the food and beverage industry has an interest in confusing the picture. If people are selling or using a product, the best thing is for them not have a clear reason to change their behavior. All that needs to happen is for them to be able say, ‘well, it’s not clear, and we don’t really know what’s going on, so I’m just going to keep doing what I’m doing.’ Then the producers and sellers of that product have won.” 

“As Upton Sinclair said,” she added, “‘It is difficult to get a man to understand something when his salary depends on his not understanding it.’ When organizations like ADA appear to be promoting a product like sucralose, and they’re not always being clear about disclosing the funding, I think that’s problematic.”

In fact, some recipes in the ADA’s hub that contain Splenda are marked sponsored, such as the four-ingredient peanut butter cookies; others, such as gluten-free brownies, are not — even though the latter contains “1/4 cup plus 1 tbsp” of Splenda Sugar Blend (Splenda produces several nonnutritive sweeteners, not all of which contain sucralose). Splenda is a sponsor of the ADA’s hub.
 

Consume in Moderation?

Regarding the use of Splenda products, Robert Gabbay, MD, PhD, the ADA’s chief scientific and medical officer, said in an interview that “some people with diabetes are accustomed to regularly consuming sugar-sweetened products, which can make management of their diabetes more challenging. As highlighted in the ADA’s Standards of Care, nonnutritive sweeteners (containing few or no calories) may be an acceptable substitute for sweeteners that contain sugar and calories when consumed in moderation. By providing a diabetes-friendly way to prepare foods people are used to eating, we can meet people where they are in offering support to effectively manage their diabetes.”

Of course, “moderation” means different things to different people. “With sucralose in particular, you can bake with it, you can cook with it, and beverages and packaged foods contain it, so it’s easy to end up overconsuming foods that may be fine if they’re occasional treats but aren’t healthy choices to have every single day,” Dr. Swithers said. “If you’re having a cookie containing sucralose once a week, it’s not a big deal, but if you’re having a cookie or a brownie every day, that’s something different.”

“I think ‘everything in moderation’ is a very reasonable approach here,” Dr. Mathur said. “Anything too much is probably not good, and that includes sweeteners like sucralose and others.”

Dr. Suez, whose team is currently exploring the mechanisms through which gut bacteria interact with nonnutritive sweeteners in the pathogenesis of cardiometabolic diseases, was more circumspect.

“We believe that additional, long-term, and non–industry-sponsored studies in humans are needed before we can make a recommendation in favor or against the use of nonnutritive sweeteners,” he said.

“However, our results demonstrating that nonnutritive sweeteners are not inert, when taken together with a growing body of evidence on potential harms of these sweeteners, merit caution until additional studies are completed,” he added. “Our findings do not imply in any way that sugar consumption, shown to be harmful to human health in many studies, is superior to nonnutritive sweeteners. Sugar consumption should be minimized, especially in individuals with obesity or diabetes. Of all the options, unsweetened beverages, specifically water, seem to be the safest and best options.”

Dr. Sen, who also “tries to convince patients to have sparkling or cold bottled water,” instead of artificially sweetened soda, agreed. “If a diabetes patient is trying to choose between sugar and sucralose, I’m not sure which one is worse.”

Dr. Swithers, Dr. Mathur, Dr. Sen, and Dr. Suez declared no competing interests.

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

It seems intuitive that, because people with type 2 diabetes (T2D) generally need to avoid sugar, clinicians should recommend eating foods and using recipes containing artificial sweeteners such as sucralose instead.

Splenda, which produces sucralose and other non-sugar sweeteners (NSS), is a sponsor of the American Diabetes Association (ADA) Diabetes Food Hub. Earlier in 2024, the ADA settled a lawsuit regarding its former director of nutrition’s refusal to approve recipes containing sucralose (Splenda), which she believed “flew in the face of the ADA’s mission.” 

Experts agree that, while artificial sweeteners may help in certain scenarios, they can also be harmful.

“There’s not a lot of evidence that sweeteners like sucralose provide significant benefits, especially over the long term,” said Susan Swithers, PhD, professor, department of psychological sciences and associate dean for faculty affairs at Purdue University, West Lafayette, Indiana.

Dr. Swithers authored an article several years ago cautioning that consuming nonnutritive sweeteners in beverages not only fails to prevent disease but also is associated with an increase in risks for the same health outcomes associated with sugar-sweetened beverages, including T2D, cardiovascular disease, hypertension, and stroke.

“At this point, we have pretty good evidence that these chemicals that were once touted as being completely inert are, in fact, not inert,” she said. “We know that they’re unlikely to be toxic in the short term, but they are not benign, and they have consequences. Right now, we have little understanding of the outcomes of consumption of these products chronically.”
 

What the Science Says

In 2023, the World Health Organization (WHO) released a guideline on NSS that recommended against their use for weight control or to reduce the risk for noncommunicable diseases.

The systematic review and meta-analysis upon which the guideline is based found that high intakes of NSS were associated with increases in body mass index and, as Dr. Swithers found, risks of developing T2D, cardiovascular events, and any type of stroke, as well as hypertension, bladder cancer, and all-cause mortality.

In a press release announcing the guideline, Francesco Branca, WHO director for Nutrition and Food Safety, said, “NSS are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health.” 

The “common” NSS named by WHO included sucralose, as well as acesulfame K, aspartame, advantame, cyclamates, neotame, saccharin, stevia, and stevia derivatives.

If NSS consumption can increase T2D risk, what about people who already have T2D? 

Some research suggests that NSS may affect people with and without T2D differently, said Dr. Swithers. For example, one small study showed that sucralose enhanced glucagon-like peptide 1 release and lowered blood glucose in healthy patients but not in patients with newly diagnosed T2D.

Similarly, Jotham Suez, PhD, an assistant professor in the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, said in an interview that his group “showed for the first time in 2014 that disruption of the microbiome by artificial sweeteners is causally linked to disrupted glycemic control.” 

Recently, the team studied the impact of sucralose, aspartame, saccharin, and stevia in healthy adults and “were surprised to discover that all four sweeteners altered gut bacteria and the molecules they secrete,” he said. However, subsequent glucose tolerance tests in healthy humans showed varying results, “suggesting that human microbiome responses to the nonnutritive sweeteners we assessed are highly personalized and may lead to glycemic alterations in some, but not all, consumers depending on their microbes and the sweeteners they consume.” 

Nevertheless, a recent review led by researchers in Mexico concluded that sucralose consumption “is associated with various adverse health effects. Despite being considered safe following previous studies, recent research suggests possible links to systemic inflammation, metabolic diseases, disruptions in gut microbiota, liver damage, and toxic effects at the cellular level.” 

In addition, they wrote, “it is crucial to highlight the persistence of sucralose in the body, its ability to cross the placenta, and its presence in breast milk, raising concerns about prenatal and neonatal exposure.” 

Sabyasachi Sen, MD, a professor of biochemistry and molecular medicine at George Washington School of Medicine & Health Sciences, Washington, DC, has led and coauthored preclinical and clinical studies demonstrating the potential ill effects of sucralose and other artificial sweeteners. One showed that sucralose and acesulfame potassium–containing diet soda altered microbial taxa in two pilot studies in healthy young adults; another showed a connection between artificial sweeteners and inflammation.

But Dr. Sen’s current work is directed at his team’s finding that sucralose promotes the accumulation of reactive oxygen species and adipogenesis in human stem cells, he said in an interview. “It is essentially an additive that is clearly harmful to cells. Our concern is that stem cells are going to remain in the system for a long period of time. If it is causing inflammation in these cells, then that may lead to adverse outcomes.”

Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment & Education Center at Cedars-Sinai in Los Angeles, California, is the principal investigator of a recent study suggesting that non-aspartame NSS and aspartame alone may alter the structure and function of the stool and duodenal microbiomes. Levels of circulating inflammatory markers were also altered in participants who consumed artificial sweeteners, compared with control participants who did not.

In addition to these potential adverse effects, “we have to think about the fact that patients with diabetes often have other comorbidities like obesity and are at higher risk for cardiovascular disease and other conditions,” she said in an interview. “If you’re taking a patient who’s already at risk for those things and you don’t have a detailed discussion with them about pros and cons, you’re doing them a disservice.” 
 

Industry Interests

Addressing the largely negative but varying findings, Dr. Swithers said, “one of the difficulties with getting clear answers about the science is that the food and beverage industry has an interest in confusing the picture. If people are selling or using a product, the best thing is for them not have a clear reason to change their behavior. All that needs to happen is for them to be able say, ‘well, it’s not clear, and we don’t really know what’s going on, so I’m just going to keep doing what I’m doing.’ Then the producers and sellers of that product have won.” 

“As Upton Sinclair said,” she added, “‘It is difficult to get a man to understand something when his salary depends on his not understanding it.’ When organizations like ADA appear to be promoting a product like sucralose, and they’re not always being clear about disclosing the funding, I think that’s problematic.”

In fact, some recipes in the ADA’s hub that contain Splenda are marked sponsored, such as the four-ingredient peanut butter cookies; others, such as gluten-free brownies, are not — even though the latter contains “1/4 cup plus 1 tbsp” of Splenda Sugar Blend (Splenda produces several nonnutritive sweeteners, not all of which contain sucralose). Splenda is a sponsor of the ADA’s hub.
 

Consume in Moderation?

Regarding the use of Splenda products, Robert Gabbay, MD, PhD, the ADA’s chief scientific and medical officer, said in an interview that “some people with diabetes are accustomed to regularly consuming sugar-sweetened products, which can make management of their diabetes more challenging. As highlighted in the ADA’s Standards of Care, nonnutritive sweeteners (containing few or no calories) may be an acceptable substitute for sweeteners that contain sugar and calories when consumed in moderation. By providing a diabetes-friendly way to prepare foods people are used to eating, we can meet people where they are in offering support to effectively manage their diabetes.”

Of course, “moderation” means different things to different people. “With sucralose in particular, you can bake with it, you can cook with it, and beverages and packaged foods contain it, so it’s easy to end up overconsuming foods that may be fine if they’re occasional treats but aren’t healthy choices to have every single day,” Dr. Swithers said. “If you’re having a cookie containing sucralose once a week, it’s not a big deal, but if you’re having a cookie or a brownie every day, that’s something different.”

“I think ‘everything in moderation’ is a very reasonable approach here,” Dr. Mathur said. “Anything too much is probably not good, and that includes sweeteners like sucralose and others.”

Dr. Suez, whose team is currently exploring the mechanisms through which gut bacteria interact with nonnutritive sweeteners in the pathogenesis of cardiometabolic diseases, was more circumspect.

“We believe that additional, long-term, and non–industry-sponsored studies in humans are needed before we can make a recommendation in favor or against the use of nonnutritive sweeteners,” he said.

“However, our results demonstrating that nonnutritive sweeteners are not inert, when taken together with a growing body of evidence on potential harms of these sweeteners, merit caution until additional studies are completed,” he added. “Our findings do not imply in any way that sugar consumption, shown to be harmful to human health in many studies, is superior to nonnutritive sweeteners. Sugar consumption should be minimized, especially in individuals with obesity or diabetes. Of all the options, unsweetened beverages, specifically water, seem to be the safest and best options.”

Dr. Sen, who also “tries to convince patients to have sparkling or cold bottled water,” instead of artificially sweetened soda, agreed. “If a diabetes patient is trying to choose between sugar and sucralose, I’m not sure which one is worse.”

Dr. Swithers, Dr. Mathur, Dr. Sen, and Dr. Suez declared no competing interests.

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

It seems intuitive that, because people with type 2 diabetes (T2D) generally need to avoid sugar, clinicians should recommend eating foods and using recipes containing artificial sweeteners such as sucralose instead.

Splenda, which produces sucralose and other non-sugar sweeteners (NSS), is a sponsor of the American Diabetes Association (ADA) Diabetes Food Hub. Earlier in 2024, the ADA settled a lawsuit regarding its former director of nutrition’s refusal to approve recipes containing sucralose (Splenda), which she believed “flew in the face of the ADA’s mission.” 

Experts agree that, while artificial sweeteners may help in certain scenarios, they can also be harmful.

“There’s not a lot of evidence that sweeteners like sucralose provide significant benefits, especially over the long term,” said Susan Swithers, PhD, professor, department of psychological sciences and associate dean for faculty affairs at Purdue University, West Lafayette, Indiana.

Dr. Swithers authored an article several years ago cautioning that consuming nonnutritive sweeteners in beverages not only fails to prevent disease but also is associated with an increase in risks for the same health outcomes associated with sugar-sweetened beverages, including T2D, cardiovascular disease, hypertension, and stroke.

“At this point, we have pretty good evidence that these chemicals that were once touted as being completely inert are, in fact, not inert,” she said. “We know that they’re unlikely to be toxic in the short term, but they are not benign, and they have consequences. Right now, we have little understanding of the outcomes of consumption of these products chronically.”
 

What the Science Says

In 2023, the World Health Organization (WHO) released a guideline on NSS that recommended against their use for weight control or to reduce the risk for noncommunicable diseases.

The systematic review and meta-analysis upon which the guideline is based found that high intakes of NSS were associated with increases in body mass index and, as Dr. Swithers found, risks of developing T2D, cardiovascular events, and any type of stroke, as well as hypertension, bladder cancer, and all-cause mortality.

In a press release announcing the guideline, Francesco Branca, WHO director for Nutrition and Food Safety, said, “NSS are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health.” 

The “common” NSS named by WHO included sucralose, as well as acesulfame K, aspartame, advantame, cyclamates, neotame, saccharin, stevia, and stevia derivatives.

If NSS consumption can increase T2D risk, what about people who already have T2D? 

Some research suggests that NSS may affect people with and without T2D differently, said Dr. Swithers. For example, one small study showed that sucralose enhanced glucagon-like peptide 1 release and lowered blood glucose in healthy patients but not in patients with newly diagnosed T2D.

Similarly, Jotham Suez, PhD, an assistant professor in the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, said in an interview that his group “showed for the first time in 2014 that disruption of the microbiome by artificial sweeteners is causally linked to disrupted glycemic control.” 

Recently, the team studied the impact of sucralose, aspartame, saccharin, and stevia in healthy adults and “were surprised to discover that all four sweeteners altered gut bacteria and the molecules they secrete,” he said. However, subsequent glucose tolerance tests in healthy humans showed varying results, “suggesting that human microbiome responses to the nonnutritive sweeteners we assessed are highly personalized and may lead to glycemic alterations in some, but not all, consumers depending on their microbes and the sweeteners they consume.” 

Nevertheless, a recent review led by researchers in Mexico concluded that sucralose consumption “is associated with various adverse health effects. Despite being considered safe following previous studies, recent research suggests possible links to systemic inflammation, metabolic diseases, disruptions in gut microbiota, liver damage, and toxic effects at the cellular level.” 

In addition, they wrote, “it is crucial to highlight the persistence of sucralose in the body, its ability to cross the placenta, and its presence in breast milk, raising concerns about prenatal and neonatal exposure.” 

Sabyasachi Sen, MD, a professor of biochemistry and molecular medicine at George Washington School of Medicine & Health Sciences, Washington, DC, has led and coauthored preclinical and clinical studies demonstrating the potential ill effects of sucralose and other artificial sweeteners. One showed that sucralose and acesulfame potassium–containing diet soda altered microbial taxa in two pilot studies in healthy young adults; another showed a connection between artificial sweeteners and inflammation.

But Dr. Sen’s current work is directed at his team’s finding that sucralose promotes the accumulation of reactive oxygen species and adipogenesis in human stem cells, he said in an interview. “It is essentially an additive that is clearly harmful to cells. Our concern is that stem cells are going to remain in the system for a long period of time. If it is causing inflammation in these cells, then that may lead to adverse outcomes.”

Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment & Education Center at Cedars-Sinai in Los Angeles, California, is the principal investigator of a recent study suggesting that non-aspartame NSS and aspartame alone may alter the structure and function of the stool and duodenal microbiomes. Levels of circulating inflammatory markers were also altered in participants who consumed artificial sweeteners, compared with control participants who did not.

In addition to these potential adverse effects, “we have to think about the fact that patients with diabetes often have other comorbidities like obesity and are at higher risk for cardiovascular disease and other conditions,” she said in an interview. “If you’re taking a patient who’s already at risk for those things and you don’t have a detailed discussion with them about pros and cons, you’re doing them a disservice.” 
 

Industry Interests

Addressing the largely negative but varying findings, Dr. Swithers said, “one of the difficulties with getting clear answers about the science is that the food and beverage industry has an interest in confusing the picture. If people are selling or using a product, the best thing is for them not have a clear reason to change their behavior. All that needs to happen is for them to be able say, ‘well, it’s not clear, and we don’t really know what’s going on, so I’m just going to keep doing what I’m doing.’ Then the producers and sellers of that product have won.” 

“As Upton Sinclair said,” she added, “‘It is difficult to get a man to understand something when his salary depends on his not understanding it.’ When organizations like ADA appear to be promoting a product like sucralose, and they’re not always being clear about disclosing the funding, I think that’s problematic.”

In fact, some recipes in the ADA’s hub that contain Splenda are marked sponsored, such as the four-ingredient peanut butter cookies; others, such as gluten-free brownies, are not — even though the latter contains “1/4 cup plus 1 tbsp” of Splenda Sugar Blend (Splenda produces several nonnutritive sweeteners, not all of which contain sucralose). Splenda is a sponsor of the ADA’s hub.
 

Consume in Moderation?

Regarding the use of Splenda products, Robert Gabbay, MD, PhD, the ADA’s chief scientific and medical officer, said in an interview that “some people with diabetes are accustomed to regularly consuming sugar-sweetened products, which can make management of their diabetes more challenging. As highlighted in the ADA’s Standards of Care, nonnutritive sweeteners (containing few or no calories) may be an acceptable substitute for sweeteners that contain sugar and calories when consumed in moderation. By providing a diabetes-friendly way to prepare foods people are used to eating, we can meet people where they are in offering support to effectively manage their diabetes.”

Of course, “moderation” means different things to different people. “With sucralose in particular, you can bake with it, you can cook with it, and beverages and packaged foods contain it, so it’s easy to end up overconsuming foods that may be fine if they’re occasional treats but aren’t healthy choices to have every single day,” Dr. Swithers said. “If you’re having a cookie containing sucralose once a week, it’s not a big deal, but if you’re having a cookie or a brownie every day, that’s something different.”

“I think ‘everything in moderation’ is a very reasonable approach here,” Dr. Mathur said. “Anything too much is probably not good, and that includes sweeteners like sucralose and others.”

Dr. Suez, whose team is currently exploring the mechanisms through which gut bacteria interact with nonnutritive sweeteners in the pathogenesis of cardiometabolic diseases, was more circumspect.

“We believe that additional, long-term, and non–industry-sponsored studies in humans are needed before we can make a recommendation in favor or against the use of nonnutritive sweeteners,” he said.

“However, our results demonstrating that nonnutritive sweeteners are not inert, when taken together with a growing body of evidence on potential harms of these sweeteners, merit caution until additional studies are completed,” he added. “Our findings do not imply in any way that sugar consumption, shown to be harmful to human health in many studies, is superior to nonnutritive sweeteners. Sugar consumption should be minimized, especially in individuals with obesity or diabetes. Of all the options, unsweetened beverages, specifically water, seem to be the safest and best options.”

Dr. Sen, who also “tries to convince patients to have sparkling or cold bottled water,” instead of artificially sweetened soda, agreed. “If a diabetes patient is trying to choose between sugar and sucralose, I’m not sure which one is worse.”

Dr. Swithers, Dr. Mathur, Dr. Sen, and Dr. Suez declared no competing interests.

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

TOPLINE:

Less than 7 hours of sleep per night is common in individuals with type 1 diabetes (T1D) but is tied to poor cardiometabolic health, particularly in adolescents.

METHODOLOGY:

• Sleep is recognized as an important factor in diabetes assessment and treatment by the 2023 American Diabetes Association’s Standards of Medical Care in Diabetes, but it is unclear whether sleep may improve health outcomes across the lifespan in patients with T1D.
• This secondary analysis of the BCQR-T1D crossover trial investigated the link between sleep and cardiometabolic health in 42 adults (age, 19-60 years) and 42 adolescents (age, 12-18 years) with T1D.
• Participants had T1D duration greater than 9 months and received bromocriptine quick-release (BCQR) therapy or placebo for 4 weeks and then switched between the treatments in a separate 4-week period.
• They underwent laboratory testing and anthropometric measurements. Also, continuous glucose monitoring data were collected for a week during each treatment phase along with an accompanying insulin dosing diary.
• Participants were required to wear an actigraphy monitor on the wrist of their nondominant hand for 7 days during each treatment phase to estimate sleep duration.

TAKEAWAY:

• Most adolescents (62%) and adults (74%) with T1D reported less than 7 hours of sleep at baseline.
• Participants with insufficient sleep versus those without insufficient sleep (< 7 vs > 7 hours) had a larger waist circumference and higher mean body mass index, systolic blood pressure, and pulse pressure, as well as lower estimated insulin sensitivity and brachial artery distensibility (P < .05 for all).
• When stratified by age, only adolescents with T1D with insufficient sleep had significant differences in most health outcomes by sleep duration status, except that adults with less than 7 hours of sleep had higher pulse pressure than those with more than 7 hours of sleep.
• Compared with placebo, BCQR slightly improved sleeping parameters in adolescents by delaying their time of waking up and prolonging their time in bed.

IN PRACTICE:

“Sleep may be an important and novel target for improving health in individuals with T1D, particularly when initiated in adolescence or early in diabetes,” the authors wrote.

SOURCE:

Stacey L. Simon, PhD, and Janet K. Snell-Bergeon, PhD, University of Colorado Anschutz Medical Campus, Aurora, led this study, which was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study lacked polysomnography or melatonin assessment to quantify circadian rhythms and subjective sleep quality ratings. It also had no objective measurement of the timing of the daily pills of BCQR, which, when taken in the morning, are hypothesized to reset the circadian rhythm for hypothalamic dopamine and serotonin. The recommended sleep duration of 8 hours for adolescents was not used as the cutoff value due to too few participants who qualified. Also, this study›s findings may be affected by the fact that participants were recruited throughout the year, while adolescents show different sleeping patterns during the academic year compared with school breaks.

DISCLOSURES:

This work was supported by a JDRF grant. Two authors declared receiving equipment, honoraria for lectures, and support for conference travel, which were all unrelated to this study.

A version of this article appeared on Medscape.com.

TOPLINE:

Less than 7 hours of sleep per night is common in individuals with type 1 diabetes (T1D) but is tied to poor cardiometabolic health, particularly in adolescents.

METHODOLOGY:

• Sleep is recognized as an important factor in diabetes assessment and treatment by the 2023 American Diabetes Association’s Standards of Medical Care in Diabetes, but it is unclear whether sleep may improve health outcomes across the lifespan in patients with T1D.
• This secondary analysis of the BCQR-T1D crossover trial investigated the link between sleep and cardiometabolic health in 42 adults (age, 19-60 years) and 42 adolescents (age, 12-18 years) with T1D.
• Participants had T1D duration greater than 9 months and received bromocriptine quick-release (BCQR) therapy or placebo for 4 weeks and then switched between the treatments in a separate 4-week period.
• They underwent laboratory testing and anthropometric measurements. Also, continuous glucose monitoring data were collected for a week during each treatment phase along with an accompanying insulin dosing diary.
• Participants were required to wear an actigraphy monitor on the wrist of their nondominant hand for 7 days during each treatment phase to estimate sleep duration.

TAKEAWAY:

• Most adolescents (62%) and adults (74%) with T1D reported less than 7 hours of sleep at baseline.
• Participants with insufficient sleep versus those without insufficient sleep (< 7 vs > 7 hours) had a larger waist circumference and higher mean body mass index, systolic blood pressure, and pulse pressure, as well as lower estimated insulin sensitivity and brachial artery distensibility (P < .05 for all).
• When stratified by age, only adolescents with T1D with insufficient sleep had significant differences in most health outcomes by sleep duration status, except that adults with less than 7 hours of sleep had higher pulse pressure than those with more than 7 hours of sleep.
• Compared with placebo, BCQR slightly improved sleeping parameters in adolescents by delaying their time of waking up and prolonging their time in bed.

IN PRACTICE:

“Sleep may be an important and novel target for improving health in individuals with T1D, particularly when initiated in adolescence or early in diabetes,” the authors wrote.

SOURCE:

Stacey L. Simon, PhD, and Janet K. Snell-Bergeon, PhD, University of Colorado Anschutz Medical Campus, Aurora, led this study, which was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study lacked polysomnography or melatonin assessment to quantify circadian rhythms and subjective sleep quality ratings. It also had no objective measurement of the timing of the daily pills of BCQR, which, when taken in the morning, are hypothesized to reset the circadian rhythm for hypothalamic dopamine and serotonin. The recommended sleep duration of 8 hours for adolescents was not used as the cutoff value due to too few participants who qualified. Also, this study›s findings may be affected by the fact that participants were recruited throughout the year, while adolescents show different sleeping patterns during the academic year compared with school breaks.

DISCLOSURES:

This work was supported by a JDRF grant. Two authors declared receiving equipment, honoraria for lectures, and support for conference travel, which were all unrelated to this study.

A version of this article appeared on Medscape.com.

TOPLINE:

Less than 7 hours of sleep per night is common in individuals with type 1 diabetes (T1D) but is tied to poor cardiometabolic health, particularly in adolescents.

METHODOLOGY:

• Sleep is recognized as an important factor in diabetes assessment and treatment by the 2023 American Diabetes Association’s Standards of Medical Care in Diabetes, but it is unclear whether sleep may improve health outcomes across the lifespan in patients with T1D.
• This secondary analysis of the BCQR-T1D crossover trial investigated the link between sleep and cardiometabolic health in 42 adults (age, 19-60 years) and 42 adolescents (age, 12-18 years) with T1D.
• Participants had T1D duration greater than 9 months and received bromocriptine quick-release (BCQR) therapy or placebo for 4 weeks and then switched between the treatments in a separate 4-week period.
• They underwent laboratory testing and anthropometric measurements. Also, continuous glucose monitoring data were collected for a week during each treatment phase along with an accompanying insulin dosing diary.
• Participants were required to wear an actigraphy monitor on the wrist of their nondominant hand for 7 days during each treatment phase to estimate sleep duration.

TAKEAWAY:

• Most adolescents (62%) and adults (74%) with T1D reported less than 7 hours of sleep at baseline.
• Participants with insufficient sleep versus those without insufficient sleep (< 7 vs > 7 hours) had a larger waist circumference and higher mean body mass index, systolic blood pressure, and pulse pressure, as well as lower estimated insulin sensitivity and brachial artery distensibility (P < .05 for all).
• When stratified by age, only adolescents with T1D with insufficient sleep had significant differences in most health outcomes by sleep duration status, except that adults with less than 7 hours of sleep had higher pulse pressure than those with more than 7 hours of sleep.
• Compared with placebo, BCQR slightly improved sleeping parameters in adolescents by delaying their time of waking up and prolonging their time in bed.

IN PRACTICE:

“Sleep may be an important and novel target for improving health in individuals with T1D, particularly when initiated in adolescence or early in diabetes,” the authors wrote.

SOURCE:

Stacey L. Simon, PhD, and Janet K. Snell-Bergeon, PhD, University of Colorado Anschutz Medical Campus, Aurora, led this study, which was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study lacked polysomnography or melatonin assessment to quantify circadian rhythms and subjective sleep quality ratings. It also had no objective measurement of the timing of the daily pills of BCQR, which, when taken in the morning, are hypothesized to reset the circadian rhythm for hypothalamic dopamine and serotonin. The recommended sleep duration of 8 hours for adolescents was not used as the cutoff value due to too few participants who qualified. Also, this study›s findings may be affected by the fact that participants were recruited throughout the year, while adolescents show different sleeping patterns during the academic year compared with school breaks.

DISCLOSURES:

This work was supported by a JDRF grant. Two authors declared receiving equipment, honoraria for lectures, and support for conference travel, which were all unrelated to this study.

A version of this article appeared on Medscape.com.

You are what you eat, as the adage goes. But a growing body of evidence indicates that it’s not just what and how much you eat that influence your health. How fast and when you eat also play a role.

Research now indicates that these two factors may affect the risk for gastrointestinal problems, obesity, and type 2 diabetes (T2D). Because meal timing and speed of consumption are modifiable, they present new opportunities to change patient behavior to help prevent and perhaps address these conditions.

Not So Fast

Most people are well acquainted with the short-term gastrointestinal effects of eating too quickly, which include indigestion, gas, bloating, and nausea. But regularly eating too fast can cause long-term consequences.

Obtaining a sense of fullness is key to staving off overeating and excess caloric intake. However, it takes approximately 20 minutes for the stomach to alert the brain to feelings of fullness. Eat too quickly and the fullness signaling might not set in until you’ve consumed more calories than intended. Research links this habit to excess body weight.

The practice also can lead to gastrointestinal diseases over the long term because overeating causes food to remain in the stomach longer, thus prolonging the time that the gastric mucosa is exposed to gastric acids.

A study of 10,893 adults in Korea reported that those with the fastest eating speed (< 5 min/meal) had a 1.7 times greater likelihood of endoscopic erosive gastritis than those with the slowest times (≥ 15 min/meal). Faster eating also was linked to increased risk for functional dyspepsia in a study involving 89 young-adult female military cadets in Korea with relatively controlled eating patterns.

On the extreme end of the spectrum, researchers who performed an assessment of a competitive speed eater speculated that the observed physiological accommodation required for the role (expanding the stomach to form a large flaccid sac) makes speed eaters vulnerable to morbid obesity, gastroparesis, intractable nausea and vomiting, and the need for gastrectomy.

The risk for metabolic changes and eventual development of T2D also appear to be linked to how quickly food is consumed.

Two clinical studies conducted in Japan — a cohort study of 2050 male factory workers and a nationwide study with 197,825 participants — identified a significant association between faster eating and T2D and insulin resistance. A case-control study involving 234 patients with new onset T2D and 468 controls from Lithuania linked faster eating to a greater than twofold risk for T2D. And a Chinese cross-sectional study of 7972 adults indicated that faster eating significantly increased the risk for metabolic syndrome, elevated blood pressure, and central obesity in adults.

Various hypotheses have been proposed to explain why fast eating may upset metabolic processes, including a delayed sense of fullness contributing to spiking postprandial glucose levels, lack of time for mastication causing higher glucose concentrations, and the triggering of specific cytokines (eg, interleukin-1 beta and interleukin-6) that lead to insulin resistance. It is also possible that the association is the result of people who eat quickly having relatively higher body weights, which translates to a higher risk for T2D.

However, there’s an opportunity in the association of rapid meal consumption with gastrointestinal and metabolic diseases, as people can slow the speed at which they eat so they feel full before they overeat.

A 2019 study in which 21 participants were instructed to eat a 600-kcal meal at a “normal” or “slow” pace (6 minutes or 24 minutes) found that the latter group reported feeling fuller while consuming fewer calories.

This approach may not work for all patients, however. There’s evidence to suggest that tactics to slow down eating may not limit the energy intake of those who are already overweight or obese.

Patients with obesity may physiologically differ in their processing of food, according to Michael Camilleri, MD, consultant in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota.

“We have demonstrated that about 20%-25% of people with obesity actually have rapid gastric emptying,” he told this news organization. “As a result, they don’t feel full after they eat a meal and that might impact the total volume of food that they eat before they really feel full.”

The Ideal Time to Eat

It’s not only the speed at which individuals eat that may influence outcomes but when they take their meals. Research indicates that eating earlier in the day to align meals with the body’s circadian rhythms in metabolism offers health benefits.

“The focus would be to eat a meal that syncs during those daytime hours,” Collin Popp, PhD, MS, RD, a research scientist at the NYU Grossman School of Medicine in New York, told this news organization. “I typically suggest patients have their largest meal in the morning, whether that’s a large or medium-sized breakfast, or a big lunch.”

A recent cross-sectional study of 2050 participants found that having the largest meal at lunch protected against obesity (odds ratio [OR], 0.71), whereas having it at dinner increased the risk for obesity (OR, 1.67) and led to higher body mass index.

Consuming the majority of calories in meals earlier in the day may have metabolic health benefits, as well.

A 2015 randomized controlled trial involving 18 adults with obesity and T2D found that eating a high-energy breakfast and a low-energy dinner leads to reduced hyperglycemia throughout the day compared with eating a low-energy breakfast and a high-energy dinner.

Time-restricted eating (TRE), a form of intermittent fasting, also can improve metabolic health depending on the time of day.

A 2023 meta-analysis found that TRE was more effective at reducing fasting glucose levels in participants who were overweight and obese if done earlier rather than later in the day. Similarly, a 2022 study involving 82 healthy patients without diabetes or obesity found that early TRE was more effective than mid-day TRE at improving insulin sensitivity and that it improved fasting glucose and reduced total body mass and adiposity, while mid-day TRE did not.

A study that analyzed the effects of TRE in eight adult men with overweight and prediabetes found “better insulin resistance when the window of food consumption was earlier in the day,» noted endocrinologist Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Cornell Medicine with a focus on obesity medication.

Patients May Benefit From Behavioral Interventions

Patients potentially negatively affected by eating too quickly or at late hours may benefit from adopting behavioral interventions to address these tendencies. To determine if a patient is a candidate for such interventions, Dr. Popp recommends starting with a simple conversation.

“When I first meet patients, I always ask them to describe to me a typical day for how they eat — when they’re eating, what they’re eating, the food quality, who are they with — to see if there’s social aspects to it. Then try and make the recommendations based on that,” said Dr. Popp, whose work focuses on biobehavioral interventions for the treatment and prevention of obesity, T2D, and other cardiometabolic outcomes.

Dr. Tchang said she encourages her patients to be mindful of hunger and fullness cues.

“Eat if you’re hungry; don’t force yourself to eat if you’re not hungry,” she said. “If you’re not sure whether you’re hungry or not, speak to a doctor because this points to an abnormality in your appetite-regulation system, which can be helped with GLP-1 [glucagon-like peptide 1] receptor agonists.”

Adjusting what patients eat can help them improve their meal timing.

“For example, we know that a high-fiber diet or a diet that has a large amount of fat in it tends to empty from the stomach slower,” Dr. Camilleri said. “That might give a sensation of fullness that lasts longer and that might prevent, for instance, the ingestion of the next meal.”

Those trying to eat more slowly are advised to seek out foods that are hard in texture and minimally processed.

A study involving 50 patients with healthy weights found that hard foods are consumed more slowly than soft foods and that energy intake is lowest with hard, minimally processed foods. Combining hard-textured foods with explicit instructions to reduce eating speed has also been shown to be an effective strategy. For those inclined to seek out technology-based solution, evidence suggests that a self-monitoring wearable device can slow the eating rate.

Although the evidence is mounting that the timing and duration of meals have an impact on certain chronic diseases, clinicians should remember that these two factors are far from the most important contributors, Dr. Popp said.

“We also have to consider total caloric intake, food quality, sleep, alcohol use, smoking, and physical activity,” he said. “Meal timing should be considered as under the umbrella of health that is important for a lot of folks.”

A version of this article appeared on Medscape.com.

You are what you eat, as the adage goes. But a growing body of evidence indicates that it’s not just what and how much you eat that influence your health. How fast and when you eat also play a role.

Research now indicates that these two factors may affect the risk for gastrointestinal problems, obesity, and type 2 diabetes (T2D). Because meal timing and speed of consumption are modifiable, they present new opportunities to change patient behavior to help prevent and perhaps address these conditions.

Not So Fast

Most people are well acquainted with the short-term gastrointestinal effects of eating too quickly, which include indigestion, gas, bloating, and nausea. But regularly eating too fast can cause long-term consequences.

Obtaining a sense of fullness is key to staving off overeating and excess caloric intake. However, it takes approximately 20 minutes for the stomach to alert the brain to feelings of fullness. Eat too quickly and the fullness signaling might not set in until you’ve consumed more calories than intended. Research links this habit to excess body weight.

The practice also can lead to gastrointestinal diseases over the long term because overeating causes food to remain in the stomach longer, thus prolonging the time that the gastric mucosa is exposed to gastric acids.

A study of 10,893 adults in Korea reported that those with the fastest eating speed (< 5 min/meal) had a 1.7 times greater likelihood of endoscopic erosive gastritis than those with the slowest times (≥ 15 min/meal). Faster eating also was linked to increased risk for functional dyspepsia in a study involving 89 young-adult female military cadets in Korea with relatively controlled eating patterns.

On the extreme end of the spectrum, researchers who performed an assessment of a competitive speed eater speculated that the observed physiological accommodation required for the role (expanding the stomach to form a large flaccid sac) makes speed eaters vulnerable to morbid obesity, gastroparesis, intractable nausea and vomiting, and the need for gastrectomy.

The risk for metabolic changes and eventual development of T2D also appear to be linked to how quickly food is consumed.

Two clinical studies conducted in Japan — a cohort study of 2050 male factory workers and a nationwide study with 197,825 participants — identified a significant association between faster eating and T2D and insulin resistance. A case-control study involving 234 patients with new onset T2D and 468 controls from Lithuania linked faster eating to a greater than twofold risk for T2D. And a Chinese cross-sectional study of 7972 adults indicated that faster eating significantly increased the risk for metabolic syndrome, elevated blood pressure, and central obesity in adults.

Various hypotheses have been proposed to explain why fast eating may upset metabolic processes, including a delayed sense of fullness contributing to spiking postprandial glucose levels, lack of time for mastication causing higher glucose concentrations, and the triggering of specific cytokines (eg, interleukin-1 beta and interleukin-6) that lead to insulin resistance. It is also possible that the association is the result of people who eat quickly having relatively higher body weights, which translates to a higher risk for T2D.

However, there’s an opportunity in the association of rapid meal consumption with gastrointestinal and metabolic diseases, as people can slow the speed at which they eat so they feel full before they overeat.

A 2019 study in which 21 participants were instructed to eat a 600-kcal meal at a “normal” or “slow” pace (6 minutes or 24 minutes) found that the latter group reported feeling fuller while consuming fewer calories.

This approach may not work for all patients, however. There’s evidence to suggest that tactics to slow down eating may not limit the energy intake of those who are already overweight or obese.

Patients with obesity may physiologically differ in their processing of food, according to Michael Camilleri, MD, consultant in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota.

“We have demonstrated that about 20%-25% of people with obesity actually have rapid gastric emptying,” he told this news organization. “As a result, they don’t feel full after they eat a meal and that might impact the total volume of food that they eat before they really feel full.”

The Ideal Time to Eat

It’s not only the speed at which individuals eat that may influence outcomes but when they take their meals. Research indicates that eating earlier in the day to align meals with the body’s circadian rhythms in metabolism offers health benefits.

“The focus would be to eat a meal that syncs during those daytime hours,” Collin Popp, PhD, MS, RD, a research scientist at the NYU Grossman School of Medicine in New York, told this news organization. “I typically suggest patients have their largest meal in the morning, whether that’s a large or medium-sized breakfast, or a big lunch.”

A recent cross-sectional study of 2050 participants found that having the largest meal at lunch protected against obesity (odds ratio [OR], 0.71), whereas having it at dinner increased the risk for obesity (OR, 1.67) and led to higher body mass index.

Consuming the majority of calories in meals earlier in the day may have metabolic health benefits, as well.

A 2015 randomized controlled trial involving 18 adults with obesity and T2D found that eating a high-energy breakfast and a low-energy dinner leads to reduced hyperglycemia throughout the day compared with eating a low-energy breakfast and a high-energy dinner.

Time-restricted eating (TRE), a form of intermittent fasting, also can improve metabolic health depending on the time of day.

A 2023 meta-analysis found that TRE was more effective at reducing fasting glucose levels in participants who were overweight and obese if done earlier rather than later in the day. Similarly, a 2022 study involving 82 healthy patients without diabetes or obesity found that early TRE was more effective than mid-day TRE at improving insulin sensitivity and that it improved fasting glucose and reduced total body mass and adiposity, while mid-day TRE did not.

A study that analyzed the effects of TRE in eight adult men with overweight and prediabetes found “better insulin resistance when the window of food consumption was earlier in the day,» noted endocrinologist Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Cornell Medicine with a focus on obesity medication.

Patients May Benefit From Behavioral Interventions

Patients potentially negatively affected by eating too quickly or at late hours may benefit from adopting behavioral interventions to address these tendencies. To determine if a patient is a candidate for such interventions, Dr. Popp recommends starting with a simple conversation.

“When I first meet patients, I always ask them to describe to me a typical day for how they eat — when they’re eating, what they’re eating, the food quality, who are they with — to see if there’s social aspects to it. Then try and make the recommendations based on that,” said Dr. Popp, whose work focuses on biobehavioral interventions for the treatment and prevention of obesity, T2D, and other cardiometabolic outcomes.

Dr. Tchang said she encourages her patients to be mindful of hunger and fullness cues.

“Eat if you’re hungry; don’t force yourself to eat if you’re not hungry,” she said. “If you’re not sure whether you’re hungry or not, speak to a doctor because this points to an abnormality in your appetite-regulation system, which can be helped with GLP-1 [glucagon-like peptide 1] receptor agonists.”

Adjusting what patients eat can help them improve their meal timing.

“For example, we know that a high-fiber diet or a diet that has a large amount of fat in it tends to empty from the stomach slower,” Dr. Camilleri said. “That might give a sensation of fullness that lasts longer and that might prevent, for instance, the ingestion of the next meal.”

Those trying to eat more slowly are advised to seek out foods that are hard in texture and minimally processed.

A study involving 50 patients with healthy weights found that hard foods are consumed more slowly than soft foods and that energy intake is lowest with hard, minimally processed foods. Combining hard-textured foods with explicit instructions to reduce eating speed has also been shown to be an effective strategy. For those inclined to seek out technology-based solution, evidence suggests that a self-monitoring wearable device can slow the eating rate.

Although the evidence is mounting that the timing and duration of meals have an impact on certain chronic diseases, clinicians should remember that these two factors are far from the most important contributors, Dr. Popp said.

“We also have to consider total caloric intake, food quality, sleep, alcohol use, smoking, and physical activity,” he said. “Meal timing should be considered as under the umbrella of health that is important for a lot of folks.”

A version of this article appeared on Medscape.com.

You are what you eat, as the adage goes. But a growing body of evidence indicates that it’s not just what and how much you eat that influence your health. How fast and when you eat also play a role.

Research now indicates that these two factors may affect the risk for gastrointestinal problems, obesity, and type 2 diabetes (T2D). Because meal timing and speed of consumption are modifiable, they present new opportunities to change patient behavior to help prevent and perhaps address these conditions.

Not So Fast

Most people are well acquainted with the short-term gastrointestinal effects of eating too quickly, which include indigestion, gas, bloating, and nausea. But regularly eating too fast can cause long-term consequences.

Obtaining a sense of fullness is key to staving off overeating and excess caloric intake. However, it takes approximately 20 minutes for the stomach to alert the brain to feelings of fullness. Eat too quickly and the fullness signaling might not set in until you’ve consumed more calories than intended. Research links this habit to excess body weight.

The practice also can lead to gastrointestinal diseases over the long term because overeating causes food to remain in the stomach longer, thus prolonging the time that the gastric mucosa is exposed to gastric acids.

A study of 10,893 adults in Korea reported that those with the fastest eating speed (< 5 min/meal) had a 1.7 times greater likelihood of endoscopic erosive gastritis than those with the slowest times (≥ 15 min/meal). Faster eating also was linked to increased risk for functional dyspepsia in a study involving 89 young-adult female military cadets in Korea with relatively controlled eating patterns.

On the extreme end of the spectrum, researchers who performed an assessment of a competitive speed eater speculated that the observed physiological accommodation required for the role (expanding the stomach to form a large flaccid sac) makes speed eaters vulnerable to morbid obesity, gastroparesis, intractable nausea and vomiting, and the need for gastrectomy.

The risk for metabolic changes and eventual development of T2D also appear to be linked to how quickly food is consumed.

Two clinical studies conducted in Japan — a cohort study of 2050 male factory workers and a nationwide study with 197,825 participants — identified a significant association between faster eating and T2D and insulin resistance. A case-control study involving 234 patients with new onset T2D and 468 controls from Lithuania linked faster eating to a greater than twofold risk for T2D. And a Chinese cross-sectional study of 7972 adults indicated that faster eating significantly increased the risk for metabolic syndrome, elevated blood pressure, and central obesity in adults.

Various hypotheses have been proposed to explain why fast eating may upset metabolic processes, including a delayed sense of fullness contributing to spiking postprandial glucose levels, lack of time for mastication causing higher glucose concentrations, and the triggering of specific cytokines (eg, interleukin-1 beta and interleukin-6) that lead to insulin resistance. It is also possible that the association is the result of people who eat quickly having relatively higher body weights, which translates to a higher risk for T2D.

However, there’s an opportunity in the association of rapid meal consumption with gastrointestinal and metabolic diseases, as people can slow the speed at which they eat so they feel full before they overeat.

A 2019 study in which 21 participants were instructed to eat a 600-kcal meal at a “normal” or “slow” pace (6 minutes or 24 minutes) found that the latter group reported feeling fuller while consuming fewer calories.

This approach may not work for all patients, however. There’s evidence to suggest that tactics to slow down eating may not limit the energy intake of those who are already overweight or obese.

Patients with obesity may physiologically differ in their processing of food, according to Michael Camilleri, MD, consultant in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota.

“We have demonstrated that about 20%-25% of people with obesity actually have rapid gastric emptying,” he told this news organization. “As a result, they don’t feel full after they eat a meal and that might impact the total volume of food that they eat before they really feel full.”

The Ideal Time to Eat

It’s not only the speed at which individuals eat that may influence outcomes but when they take their meals. Research indicates that eating earlier in the day to align meals with the body’s circadian rhythms in metabolism offers health benefits.

“The focus would be to eat a meal that syncs during those daytime hours,” Collin Popp, PhD, MS, RD, a research scientist at the NYU Grossman School of Medicine in New York, told this news organization. “I typically suggest patients have their largest meal in the morning, whether that’s a large or medium-sized breakfast, or a big lunch.”

A recent cross-sectional study of 2050 participants found that having the largest meal at lunch protected against obesity (odds ratio [OR], 0.71), whereas having it at dinner increased the risk for obesity (OR, 1.67) and led to higher body mass index.

Consuming the majority of calories in meals earlier in the day may have metabolic health benefits, as well.

A 2015 randomized controlled trial involving 18 adults with obesity and T2D found that eating a high-energy breakfast and a low-energy dinner leads to reduced hyperglycemia throughout the day compared with eating a low-energy breakfast and a high-energy dinner.

Time-restricted eating (TRE), a form of intermittent fasting, also can improve metabolic health depending on the time of day.

A 2023 meta-analysis found that TRE was more effective at reducing fasting glucose levels in participants who were overweight and obese if done earlier rather than later in the day. Similarly, a 2022 study involving 82 healthy patients without diabetes or obesity found that early TRE was more effective than mid-day TRE at improving insulin sensitivity and that it improved fasting glucose and reduced total body mass and adiposity, while mid-day TRE did not.

A study that analyzed the effects of TRE in eight adult men with overweight and prediabetes found “better insulin resistance when the window of food consumption was earlier in the day,» noted endocrinologist Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Cornell Medicine with a focus on obesity medication.

Patients May Benefit From Behavioral Interventions

Patients potentially negatively affected by eating too quickly or at late hours may benefit from adopting behavioral interventions to address these tendencies. To determine if a patient is a candidate for such interventions, Dr. Popp recommends starting with a simple conversation.

“When I first meet patients, I always ask them to describe to me a typical day for how they eat — when they’re eating, what they’re eating, the food quality, who are they with — to see if there’s social aspects to it. Then try and make the recommendations based on that,” said Dr. Popp, whose work focuses on biobehavioral interventions for the treatment and prevention of obesity, T2D, and other cardiometabolic outcomes.

Dr. Tchang said she encourages her patients to be mindful of hunger and fullness cues.

“Eat if you’re hungry; don’t force yourself to eat if you’re not hungry,” she said. “If you’re not sure whether you’re hungry or not, speak to a doctor because this points to an abnormality in your appetite-regulation system, which can be helped with GLP-1 [glucagon-like peptide 1] receptor agonists.”

Adjusting what patients eat can help them improve their meal timing.

“For example, we know that a high-fiber diet or a diet that has a large amount of fat in it tends to empty from the stomach slower,” Dr. Camilleri said. “That might give a sensation of fullness that lasts longer and that might prevent, for instance, the ingestion of the next meal.”

Those trying to eat more slowly are advised to seek out foods that are hard in texture and minimally processed.

A study involving 50 patients with healthy weights found that hard foods are consumed more slowly than soft foods and that energy intake is lowest with hard, minimally processed foods. Combining hard-textured foods with explicit instructions to reduce eating speed has also been shown to be an effective strategy. For those inclined to seek out technology-based solution, evidence suggests that a self-monitoring wearable device can slow the eating rate.

Although the evidence is mounting that the timing and duration of meals have an impact on certain chronic diseases, clinicians should remember that these two factors are far from the most important contributors, Dr. Popp said.

“We also have to consider total caloric intake, food quality, sleep, alcohol use, smoking, and physical activity,” he said. “Meal timing should be considered as under the umbrella of health that is important for a lot of folks.”

A version of this article appeared on Medscape.com.

TOPLINE:

Tirzepatide vs basal insulins led to greater improvements in A1c and postprandial glucose (PPG) levels in patients with type 2 diabetes (T2D), regardless of different baseline PPG or fasting serum glucose (FSG) levels.

METHODOLOGY:

• Tirzepatide led to better glycemic control than insulin degludec and insulin glargine in the SURPASS-3 and SURPASS-4 trials, respectively, but the effect on FSG and PPG levels was not evaluated.
• In this post hoc analysis, the researchers assessed changes in various glycemic parameters in 3314 patients with T2D who were randomly assigned to receive tirzepatide (5, 10, or 15 mg), insulin degludec, or insulin glargine.
• Based on the median baseline glucose values, the patients were stratified into four subgroups: Low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, and high FSG/high PPG.
• The outcomes of interest were changes in FSG, PPG, A1c, and body weight from baseline to week 52.

TAKEAWAY:

• Tirzepatide and basal insulins effectively lowered A1c, PPG levels, and FSG levels at 52 weeks across all patient subgroups (all P < .05).
• All three doses of tirzepatide resulted in greater reductions in both A1c and PPG levels than in basal insulins (all P < .05).
• In the high FSG/high PPG subgroup, a greater reduction in FSG levels was observed with tirzepatide 10- and 15-mg doses vs insulin glargine (both P < .05) and insulin degludec vs tirzepatide 5 mg (P < .001).
• Furthermore, at week 52, tirzepatide led to body weight reduction (P < .05), but insulin treatment led to an increase in body weight (P < .05) in all subgroups.

IN PRACTICE:

“Treatment with tirzepatide was consistently associated with more reduced PPG levels compared with insulin treatment across subgroups, including in participants with lower baseline PPG levels, in turn leading to greater A1c reductions,” the authors wrote.

SOURCE:

This study was led by Francesco Giorgino, MD, PhD, of the Section of Internal Medicine, Endocrinology, Andrology, and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy, and was published online in Diabetes Care.

LIMITATIONS:

The limitations include post hoc nature of the study and the short treatment duration. The trials included only patients with diabetes and overweight or obesity, and therefore, the study findings may not be generalizable to other populations.

DISCLOSURES:

This study and the SURPASS trials were funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly and Company. The other authors declared having several ties with various sources, including Eli Lilly and Company.

A version of this article appeared on Medscape.com.

TOPLINE:

Tirzepatide vs basal insulins led to greater improvements in A1c and postprandial glucose (PPG) levels in patients with type 2 diabetes (T2D), regardless of different baseline PPG or fasting serum glucose (FSG) levels.

METHODOLOGY:

• Tirzepatide led to better glycemic control than insulin degludec and insulin glargine in the SURPASS-3 and SURPASS-4 trials, respectively, but the effect on FSG and PPG levels was not evaluated.
• In this post hoc analysis, the researchers assessed changes in various glycemic parameters in 3314 patients with T2D who were randomly assigned to receive tirzepatide (5, 10, or 15 mg), insulin degludec, or insulin glargine.
• Based on the median baseline glucose values, the patients were stratified into four subgroups: Low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, and high FSG/high PPG.
• The outcomes of interest were changes in FSG, PPG, A1c, and body weight from baseline to week 52.

TAKEAWAY:

• Tirzepatide and basal insulins effectively lowered A1c, PPG levels, and FSG levels at 52 weeks across all patient subgroups (all P < .05).
• All three doses of tirzepatide resulted in greater reductions in both A1c and PPG levels than in basal insulins (all P < .05).
• In the high FSG/high PPG subgroup, a greater reduction in FSG levels was observed with tirzepatide 10- and 15-mg doses vs insulin glargine (both P < .05) and insulin degludec vs tirzepatide 5 mg (P < .001).
• Furthermore, at week 52, tirzepatide led to body weight reduction (P < .05), but insulin treatment led to an increase in body weight (P < .05) in all subgroups.

IN PRACTICE:

“Treatment with tirzepatide was consistently associated with more reduced PPG levels compared with insulin treatment across subgroups, including in participants with lower baseline PPG levels, in turn leading to greater A1c reductions,” the authors wrote.

SOURCE:

This study was led by Francesco Giorgino, MD, PhD, of the Section of Internal Medicine, Endocrinology, Andrology, and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy, and was published online in Diabetes Care.

LIMITATIONS:

The limitations include post hoc nature of the study and the short treatment duration. The trials included only patients with diabetes and overweight or obesity, and therefore, the study findings may not be generalizable to other populations.

DISCLOSURES:

This study and the SURPASS trials were funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly and Company. The other authors declared having several ties with various sources, including Eli Lilly and Company.

A version of this article appeared on Medscape.com.

TOPLINE:

Tirzepatide vs basal insulins led to greater improvements in A1c and postprandial glucose (PPG) levels in patients with type 2 diabetes (T2D), regardless of different baseline PPG or fasting serum glucose (FSG) levels.

METHODOLOGY:

• Tirzepatide led to better glycemic control than insulin degludec and insulin glargine in the SURPASS-3 and SURPASS-4 trials, respectively, but the effect on FSG and PPG levels was not evaluated.
• In this post hoc analysis, the researchers assessed changes in various glycemic parameters in 3314 patients with T2D who were randomly assigned to receive tirzepatide (5, 10, or 15 mg), insulin degludec, or insulin glargine.
• Based on the median baseline glucose values, the patients were stratified into four subgroups: Low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, and high FSG/high PPG.
• The outcomes of interest were changes in FSG, PPG, A1c, and body weight from baseline to week 52.

TAKEAWAY:

• Tirzepatide and basal insulins effectively lowered A1c, PPG levels, and FSG levels at 52 weeks across all patient subgroups (all P < .05).
• All three doses of tirzepatide resulted in greater reductions in both A1c and PPG levels than in basal insulins (all P < .05).
• In the high FSG/high PPG subgroup, a greater reduction in FSG levels was observed with tirzepatide 10- and 15-mg doses vs insulin glargine (both P < .05) and insulin degludec vs tirzepatide 5 mg (P < .001).
• Furthermore, at week 52, tirzepatide led to body weight reduction (P < .05), but insulin treatment led to an increase in body weight (P < .05) in all subgroups.

IN PRACTICE:

“Treatment with tirzepatide was consistently associated with more reduced PPG levels compared with insulin treatment across subgroups, including in participants with lower baseline PPG levels, in turn leading to greater A1c reductions,” the authors wrote.

SOURCE:

This study was led by Francesco Giorgino, MD, PhD, of the Section of Internal Medicine, Endocrinology, Andrology, and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy, and was published online in Diabetes Care.

LIMITATIONS:

The limitations include post hoc nature of the study and the short treatment duration. The trials included only patients with diabetes and overweight or obesity, and therefore, the study findings may not be generalizable to other populations.

DISCLOSURES:

This study and the SURPASS trials were funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly and Company. The other authors declared having several ties with various sources, including Eli Lilly and Company.

A version of this article appeared on Medscape.com.

TOPLINE:

The inclusion of sugar-substitute sweeteners and sweetness enhancers in a sugar-reduced maintenance diet following weight loss improves weight maintenance as well as well-being in adults, with no increases in type 2 diabetes or cardiovascular disease risk compared with a diet excluding the sweeteners, a randomized trial showed.

The study also showed that among overweight or obese children, greater reductions in uncontrolled eating were observed among those receiving the sweeteners.

The findings counter previous reports that raised concerns about the non-sugar sweeteners, including recent research from the World Health Organization suggesting no benefits in weight control and a possible increase in the risk for type 2 diabetes or cardiovascular disease with the sweeteners.

METHODOLOGY:

• The findings are from an exploratory analysis of the multicenter, randomized SWEET trial.
• The trial involved 341 adults with overweight or obesity (aged 18-65 years, 71% women, body mass index [BMI] ≥ 25) and 38 children with overweight (aged 6-12 years, 60% girls, BMI-for-age > 85th percentile), recruited in Denmark, Spain, Greece, and the Netherlands through webpages, social media, newspapers, and registries.
• For the first 2 months of the trial, adults were instructed to follow a low-energy diet (the Cambridge Weight Plan) with the goal of achieving at least 5% weight loss, while children received dietary advice to maintain body weight.
• In the subsequent 10 months, adults as well as children were randomized to healthy diets that either consisted of less than 10% of calories from added sugar but permitted foods and drinks with sweeteners and sweetness enhancers, or the same diet but not allowing the use of the sweeteners or sweetness enhancers.
• Participants had weight, BMI, anthropometry, and risk markers for type 2 diabetes and cardiovascular disease monitored at the trial’s baseline, as well as at 2, 6, and 12 months.
• In addition, participants completed food frequency questionnaires and provided urine samples to assess biomarkers of the sweeteners, fructose and sucrose, in order to measure compliance with the dietary instructions.

TAKEAWAY:

• While the sweetener and non-sweetener groups both had decreases in consumption of products high in sugar, the reduction was significantly higher in the group that allowed use of the sweeteners (P = .002).
• In the intention-to-treat analyses, adults (n = 277) permitted sweeteners showed a small but significantly greater weight loss maintenance after 1 year than the non-sweetener group (average weight loss, 7.2 kg vs 5.6 kg; P = .029).
• Among 203 participants who completed the trial, there were no differences between the groups in terms of markers for type 2 diabetes and cardiovascular disease.
• There were also no differences between the groups in terms of subjective appetite sensations and appetite hormones in a subgroup of 104 patients.
• In an analysis of 22 children who completed the study, there were no differences in BMI-for-age z scores between sweetener and non-sweetener groups.
• In terms of effects on eating behavior, adults in the sweetener group reported greater diet satisfaction when eating out (P = .03), increased positive mood (P = .013), and reduced craving for sweet food (P = .034) at 6 months than in the non-sweetener group.
• Conversely, those receiving no sweeteners had a greater liking bias for sweet vs savory foods at 6 months (P = .023) and 12 months (P = .005).
• There were no differences between the groups in reported physical activity or quality of life.
• However, among children with higher uncontrolled eating scores at baseline, the uncontrolled eating scores at 12 months were significantly lower among children who were allowed the sugar-substitute sweeteners vs the non-sweetener children (P = .021).

IN PRACTICE:

“Our findings suggest that the inclusion of low/no energy-sweetened products may benefit children who show high levels of uncontrolled eating,” said the study’s co-lead author, Clarissa Dakin, of the Appetite Control and Energy Balance Research Group at the University of Leeds, Leeds, England, in a press statement.

“Together, these findings provide important insights for the ongoing reevaluation of food additive sweeteners by the European Food Safety Authority and other health agencies worldwide,” she said.

Coauthor Jason Halford, head of the School of Psychology at the University of Leeds, added in the press statement that “the use of low-calorie sweeteners in weight management has been questioned, in part because of the link between their use and apparent weight gain in observational studies.”

“However, increasingly, it is becoming apparent that is not the case in long-term studies,” said a study co-author in a press statement.”

SOURCE:

The findings from the two abstracts will be presented in May at the European Association for the Study of Obesity. The study abstracts were issued in advance.

LIMITATIONS:

Some of the results, particularly in children’s subgroups, were limited by the relatively low number of children, underscoring the need for future studies on the issue, the authors noted.

DISCLOSURES:

Dr. Halford has received research funding from the American Beverage Association.

A version of this article appeared on Medscape.com.

TOPLINE:

The inclusion of sugar-substitute sweeteners and sweetness enhancers in a sugar-reduced maintenance diet following weight loss improves weight maintenance as well as well-being in adults, with no increases in type 2 diabetes or cardiovascular disease risk compared with a diet excluding the sweeteners, a randomized trial showed.

The study also showed that among overweight or obese children, greater reductions in uncontrolled eating were observed among those receiving the sweeteners.

The findings counter previous reports that raised concerns about the non-sugar sweeteners, including recent research from the World Health Organization suggesting no benefits in weight control and a possible increase in the risk for type 2 diabetes or cardiovascular disease with the sweeteners.

METHODOLOGY:

• The findings are from an exploratory analysis of the multicenter, randomized SWEET trial.
• The trial involved 341 adults with overweight or obesity (aged 18-65 years, 71% women, body mass index [BMI] ≥ 25) and 38 children with overweight (aged 6-12 years, 60% girls, BMI-for-age > 85th percentile), recruited in Denmark, Spain, Greece, and the Netherlands through webpages, social media, newspapers, and registries.
• For the first 2 months of the trial, adults were instructed to follow a low-energy diet (the Cambridge Weight Plan) with the goal of achieving at least 5% weight loss, while children received dietary advice to maintain body weight.
• In the subsequent 10 months, adults as well as children were randomized to healthy diets that either consisted of less than 10% of calories from added sugar but permitted foods and drinks with sweeteners and sweetness enhancers, or the same diet but not allowing the use of the sweeteners or sweetness enhancers.
• Participants had weight, BMI, anthropometry, and risk markers for type 2 diabetes and cardiovascular disease monitored at the trial’s baseline, as well as at 2, 6, and 12 months.
• In addition, participants completed food frequency questionnaires and provided urine samples to assess biomarkers of the sweeteners, fructose and sucrose, in order to measure compliance with the dietary instructions.

TAKEAWAY:

• While the sweetener and non-sweetener groups both had decreases in consumption of products high in sugar, the reduction was significantly higher in the group that allowed use of the sweeteners (P = .002).
• In the intention-to-treat analyses, adults (n = 277) permitted sweeteners showed a small but significantly greater weight loss maintenance after 1 year than the non-sweetener group (average weight loss, 7.2 kg vs 5.6 kg; P = .029).
• Among 203 participants who completed the trial, there were no differences between the groups in terms of markers for type 2 diabetes and cardiovascular disease.
• There were also no differences between the groups in terms of subjective appetite sensations and appetite hormones in a subgroup of 104 patients.
• In an analysis of 22 children who completed the study, there were no differences in BMI-for-age z scores between sweetener and non-sweetener groups.
• In terms of effects on eating behavior, adults in the sweetener group reported greater diet satisfaction when eating out (P = .03), increased positive mood (P = .013), and reduced craving for sweet food (P = .034) at 6 months than in the non-sweetener group.
• Conversely, those receiving no sweeteners had a greater liking bias for sweet vs savory foods at 6 months (P = .023) and 12 months (P = .005).
• There were no differences between the groups in reported physical activity or quality of life.
• However, among children with higher uncontrolled eating scores at baseline, the uncontrolled eating scores at 12 months were significantly lower among children who were allowed the sugar-substitute sweeteners vs the non-sweetener children (P = .021).

IN PRACTICE:

“Our findings suggest that the inclusion of low/no energy-sweetened products may benefit children who show high levels of uncontrolled eating,” said the study’s co-lead author, Clarissa Dakin, of the Appetite Control and Energy Balance Research Group at the University of Leeds, Leeds, England, in a press statement.

“Together, these findings provide important insights for the ongoing reevaluation of food additive sweeteners by the European Food Safety Authority and other health agencies worldwide,” she said.

Coauthor Jason Halford, head of the School of Psychology at the University of Leeds, added in the press statement that “the use of low-calorie sweeteners in weight management has been questioned, in part because of the link between their use and apparent weight gain in observational studies.”

“However, increasingly, it is becoming apparent that is not the case in long-term studies,” said a study co-author in a press statement.”

SOURCE:

The findings from the two abstracts will be presented in May at the European Association for the Study of Obesity. The study abstracts were issued in advance.

LIMITATIONS:

Some of the results, particularly in children’s subgroups, were limited by the relatively low number of children, underscoring the need for future studies on the issue, the authors noted.

DISCLOSURES:

Dr. Halford has received research funding from the American Beverage Association.

A version of this article appeared on Medscape.com.

TOPLINE:

The inclusion of sugar-substitute sweeteners and sweetness enhancers in a sugar-reduced maintenance diet following weight loss improves weight maintenance as well as well-being in adults, with no increases in type 2 diabetes or cardiovascular disease risk compared with a diet excluding the sweeteners, a randomized trial showed.

The study also showed that among overweight or obese children, greater reductions in uncontrolled eating were observed among those receiving the sweeteners.

The findings counter previous reports that raised concerns about the non-sugar sweeteners, including recent research from the World Health Organization suggesting no benefits in weight control and a possible increase in the risk for type 2 diabetes or cardiovascular disease with the sweeteners.

METHODOLOGY:

• The findings are from an exploratory analysis of the multicenter, randomized SWEET trial.
• The trial involved 341 adults with overweight or obesity (aged 18-65 years, 71% women, body mass index [BMI] ≥ 25) and 38 children with overweight (aged 6-12 years, 60% girls, BMI-for-age > 85th percentile), recruited in Denmark, Spain, Greece, and the Netherlands through webpages, social media, newspapers, and registries.
• For the first 2 months of the trial, adults were instructed to follow a low-energy diet (the Cambridge Weight Plan) with the goal of achieving at least 5% weight loss, while children received dietary advice to maintain body weight.
• In the subsequent 10 months, adults as well as children were randomized to healthy diets that either consisted of less than 10% of calories from added sugar but permitted foods and drinks with sweeteners and sweetness enhancers, or the same diet but not allowing the use of the sweeteners or sweetness enhancers.
• Participants had weight, BMI, anthropometry, and risk markers for type 2 diabetes and cardiovascular disease monitored at the trial’s baseline, as well as at 2, 6, and 12 months.
• In addition, participants completed food frequency questionnaires and provided urine samples to assess biomarkers of the sweeteners, fructose and sucrose, in order to measure compliance with the dietary instructions.

TAKEAWAY:

• While the sweetener and non-sweetener groups both had decreases in consumption of products high in sugar, the reduction was significantly higher in the group that allowed use of the sweeteners (P = .002).
• In the intention-to-treat analyses, adults (n = 277) permitted sweeteners showed a small but significantly greater weight loss maintenance after 1 year than the non-sweetener group (average weight loss, 7.2 kg vs 5.6 kg; P = .029).
• Among 203 participants who completed the trial, there were no differences between the groups in terms of markers for type 2 diabetes and cardiovascular disease.
• There were also no differences between the groups in terms of subjective appetite sensations and appetite hormones in a subgroup of 104 patients.
• In an analysis of 22 children who completed the study, there were no differences in BMI-for-age z scores between sweetener and non-sweetener groups.
• In terms of effects on eating behavior, adults in the sweetener group reported greater diet satisfaction when eating out (P = .03), increased positive mood (P = .013), and reduced craving for sweet food (P = .034) at 6 months than in the non-sweetener group.
• Conversely, those receiving no sweeteners had a greater liking bias for sweet vs savory foods at 6 months (P = .023) and 12 months (P = .005).
• There were no differences between the groups in reported physical activity or quality of life.
• However, among children with higher uncontrolled eating scores at baseline, the uncontrolled eating scores at 12 months were significantly lower among children who were allowed the sugar-substitute sweeteners vs the non-sweetener children (P = .021).

IN PRACTICE:

“Our findings suggest that the inclusion of low/no energy-sweetened products may benefit children who show high levels of uncontrolled eating,” said the study’s co-lead author, Clarissa Dakin, of the Appetite Control and Energy Balance Research Group at the University of Leeds, Leeds, England, in a press statement.

“Together, these findings provide important insights for the ongoing reevaluation of food additive sweeteners by the European Food Safety Authority and other health agencies worldwide,” she said.

Coauthor Jason Halford, head of the School of Psychology at the University of Leeds, added in the press statement that “the use of low-calorie sweeteners in weight management has been questioned, in part because of the link between their use and apparent weight gain in observational studies.”

“However, increasingly, it is becoming apparent that is not the case in long-term studies,” said a study co-author in a press statement.”

SOURCE:

The findings from the two abstracts will be presented in May at the European Association for the Study of Obesity. The study abstracts were issued in advance.

LIMITATIONS:

Some of the results, particularly in children’s subgroups, were limited by the relatively low number of children, underscoring the need for future studies on the issue, the authors noted.

DISCLOSURES:

Dr. Halford has received research funding from the American Beverage Association.

A version of this article appeared on Medscape.com.

TOPLINE:

More than a billion children, adolescents, and adults are living with obesity, globally, with rates of obesity among children and adolescents quadrupling between 1990 and 2022.

Obesity rates nearly tripled among adult men and more than doubled among women during the time period, according to results from a collaboration between the NCD Risk Factor Collaboration and the World Health Organization (WHO).

The rates of being underweight have meanwhile declined, making obesity now the most common form of malnutrition in most regions.

METHODOLOGY:

In this global analysis, the authors evaluated 3663 population-based studies conducted in 200 countries and territories, with data on 222 million participants in the general population, including height and weight.

Trends were established according to categories of body mass index (BMI) in groups of adults aged 20 years or older, representing 150 million individuals, and 63 million school-aged children and adolescents aged 5-19 years, spanning from 1990 to 2022.

Assessments of adults focus on the individual and combined prevalence of underweight (BMI < 18.5 kg/m²) and obesity (BMI ≥ 30 kg/m²).

For school-aged children and adolescents, assessments were for thinness (BMI < 2 standard deviation [SD] below the median of the WHO growth reference) and obesity (BMI > 2 SD above the median).

TAKEAWAY:

The combined prevalence of obesity as well as underweight increased over the study period in most countries for women (162 countries, 81%) and men (140 countries, 70%), with increases driven by increases in obesity in nearly all countries, while underweight or thinness rates decreased.

In 2022, obesity rates were higher than underweight in 177 countries (89%) for women and 145 countries (73%) for men.

Likewise, among school-aged children and adolescents, obesity in 2022 was more prevalent than thinness among girls in 130 countries (67%) and boys in 125 countries (63%), while thinness was more prevalent in only 18% and 21% of the countries, respectively.

In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, as well as in countries in the Middle East and North Africa.

Among school-aged children, the countries with the highest combined prevalence of underweight and obesity were Polynesia and Micronesia and the Caribbean for both sexes and Chile and Qatar for boys.

The prevalence of obesity surpassed 60% among women in eight countries (4%) and men in six countries (3%), all in Polynesia and Micronesia.

In the United States, the obesity rate increased from 21.2% in 1990 to 43.8% in 2022 for women and from 16.9% to 41.6% in 2022 for men.

As of 2022, the prevalence of obesity in the United States ranked 36th highest in the world for women and 10th highest in the world for men.

IN PRACTICE:

“It is very concerning that the epidemic of obesity that was evident among adults in much of the world in 1990 is now mirrored in school-aged children and adolescents,” senior author Majid Ezzati, PhD, of Imperial College of London, said in a press statement.

“At the same time, hundreds of millions are still affected by undernutrition, particularly in some of the poorest parts of the world,” he said. “To successfully tackle both forms of malnutrition, it is vital we significantly improve the availability and affordability of healthy, nutritious foods.”

Tedros Adhanom Ghebreyesus, PhD, WHO Director-General, added in the press statement that “this new study highlights the importance of preventing and managing obesity from early life to adulthood, through diet, physical activity, and adequate care, as needed.

“Getting back on track to meet the global targets for curbing obesity will take the work of governments and communities, supported by evidence-based policies from WHO and national public health agencies,” he said.

“Importantly, it requires the cooperation of the private sector, which must be accountable for the health impacts of their products.”

SOURCE:

The study was published on February 29, 2024, in The Lancet. The study was conducted by the NCD Risk Factor Collaboration and the WHO.

LIMITATIONS:

Data differences in countries included that some had limited data and three had none, requiring some estimates to be formed using data from other countries. Data availability was also lower among the youngest and oldest patients, increasing uncertainty of data in those age groups. In addition, data from health surveys can be subject to error, and BMI can be an imperfect measure of the extent or distribution of body fat.

DISCLOSURES:

The study was funded by UK Medical Research Council, UK Research and Innovation, and the European Commission.
 

A version of this article appeared on Medscape.com.

TOPLINE:

More than a billion children, adolescents, and adults are living with obesity, globally, with rates of obesity among children and adolescents quadrupling between 1990 and 2022.

Obesity rates nearly tripled among adult men and more than doubled among women during the time period, according to results from a collaboration between the NCD Risk Factor Collaboration and the World Health Organization (WHO).

The rates of being underweight have meanwhile declined, making obesity now the most common form of malnutrition in most regions.

METHODOLOGY:

In this global analysis, the authors evaluated 3663 population-based studies conducted in 200 countries and territories, with data on 222 million participants in the general population, including height and weight.

Trends were established according to categories of body mass index (BMI) in groups of adults aged 20 years or older, representing 150 million individuals, and 63 million school-aged children and adolescents aged 5-19 years, spanning from 1990 to 2022.

Assessments of adults focus on the individual and combined prevalence of underweight (BMI < 18.5 kg/m²) and obesity (BMI ≥ 30 kg/m²).

For school-aged children and adolescents, assessments were for thinness (BMI < 2 standard deviation [SD] below the median of the WHO growth reference) and obesity (BMI > 2 SD above the median).

TAKEAWAY:

The combined prevalence of obesity as well as underweight increased over the study period in most countries for women (162 countries, 81%) and men (140 countries, 70%), with increases driven by increases in obesity in nearly all countries, while underweight or thinness rates decreased.

In 2022, obesity rates were higher than underweight in 177 countries (89%) for women and 145 countries (73%) for men.

Likewise, among school-aged children and adolescents, obesity in 2022 was more prevalent than thinness among girls in 130 countries (67%) and boys in 125 countries (63%), while thinness was more prevalent in only 18% and 21% of the countries, respectively.

In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, as well as in countries in the Middle East and North Africa.

Among school-aged children, the countries with the highest combined prevalence of underweight and obesity were Polynesia and Micronesia and the Caribbean for both sexes and Chile and Qatar for boys.

The prevalence of obesity surpassed 60% among women in eight countries (4%) and men in six countries (3%), all in Polynesia and Micronesia.

In the United States, the obesity rate increased from 21.2% in 1990 to 43.8% in 2022 for women and from 16.9% to 41.6% in 2022 for men.

As of 2022, the prevalence of obesity in the United States ranked 36th highest in the world for women and 10th highest in the world for men.

IN PRACTICE:

“It is very concerning that the epidemic of obesity that was evident among adults in much of the world in 1990 is now mirrored in school-aged children and adolescents,” senior author Majid Ezzati, PhD, of Imperial College of London, said in a press statement.

“At the same time, hundreds of millions are still affected by undernutrition, particularly in some of the poorest parts of the world,” he said. “To successfully tackle both forms of malnutrition, it is vital we significantly improve the availability and affordability of healthy, nutritious foods.”

Tedros Adhanom Ghebreyesus, PhD, WHO Director-General, added in the press statement that “this new study highlights the importance of preventing and managing obesity from early life to adulthood, through diet, physical activity, and adequate care, as needed.

“Getting back on track to meet the global targets for curbing obesity will take the work of governments and communities, supported by evidence-based policies from WHO and national public health agencies,” he said.

“Importantly, it requires the cooperation of the private sector, which must be accountable for the health impacts of their products.”

SOURCE:

The study was published on February 29, 2024, in The Lancet. The study was conducted by the NCD Risk Factor Collaboration and the WHO.

LIMITATIONS:

Data differences in countries included that some had limited data and three had none, requiring some estimates to be formed using data from other countries. Data availability was also lower among the youngest and oldest patients, increasing uncertainty of data in those age groups. In addition, data from health surveys can be subject to error, and BMI can be an imperfect measure of the extent or distribution of body fat.

DISCLOSURES:

The study was funded by UK Medical Research Council, UK Research and Innovation, and the European Commission.
 

A version of this article appeared on Medscape.com.

TOPLINE:

More than a billion children, adolescents, and adults are living with obesity, globally, with rates of obesity among children and adolescents quadrupling between 1990 and 2022.

Obesity rates nearly tripled among adult men and more than doubled among women during the time period, according to results from a collaboration between the NCD Risk Factor Collaboration and the World Health Organization (WHO).

The rates of being underweight have meanwhile declined, making obesity now the most common form of malnutrition in most regions.

METHODOLOGY:

In this global analysis, the authors evaluated 3663 population-based studies conducted in 200 countries and territories, with data on 222 million participants in the general population, including height and weight.

Trends were established according to categories of body mass index (BMI) in groups of adults aged 20 years or older, representing 150 million individuals, and 63 million school-aged children and adolescents aged 5-19 years, spanning from 1990 to 2022.

Assessments of adults focus on the individual and combined prevalence of underweight (BMI < 18.5 kg/m²) and obesity (BMI ≥ 30 kg/m²).

For school-aged children and adolescents, assessments were for thinness (BMI < 2 standard deviation [SD] below the median of the WHO growth reference) and obesity (BMI > 2 SD above the median).

TAKEAWAY:

The combined prevalence of obesity as well as underweight increased over the study period in most countries for women (162 countries, 81%) and men (140 countries, 70%), with increases driven by increases in obesity in nearly all countries, while underweight or thinness rates decreased.

In 2022, obesity rates were higher than underweight in 177 countries (89%) for women and 145 countries (73%) for men.

Likewise, among school-aged children and adolescents, obesity in 2022 was more prevalent than thinness among girls in 130 countries (67%) and boys in 125 countries (63%), while thinness was more prevalent in only 18% and 21% of the countries, respectively.

In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, as well as in countries in the Middle East and North Africa.

Among school-aged children, the countries with the highest combined prevalence of underweight and obesity were Polynesia and Micronesia and the Caribbean for both sexes and Chile and Qatar for boys.

The prevalence of obesity surpassed 60% among women in eight countries (4%) and men in six countries (3%), all in Polynesia and Micronesia.

In the United States, the obesity rate increased from 21.2% in 1990 to 43.8% in 2022 for women and from 16.9% to 41.6% in 2022 for men.

As of 2022, the prevalence of obesity in the United States ranked 36th highest in the world for women and 10th highest in the world for men.

IN PRACTICE:

“It is very concerning that the epidemic of obesity that was evident among adults in much of the world in 1990 is now mirrored in school-aged children and adolescents,” senior author Majid Ezzati, PhD, of Imperial College of London, said in a press statement.

“At the same time, hundreds of millions are still affected by undernutrition, particularly in some of the poorest parts of the world,” he said. “To successfully tackle both forms of malnutrition, it is vital we significantly improve the availability and affordability of healthy, nutritious foods.”

Tedros Adhanom Ghebreyesus, PhD, WHO Director-General, added in the press statement that “this new study highlights the importance of preventing and managing obesity from early life to adulthood, through diet, physical activity, and adequate care, as needed.

“Getting back on track to meet the global targets for curbing obesity will take the work of governments and communities, supported by evidence-based policies from WHO and national public health agencies,” he said.

“Importantly, it requires the cooperation of the private sector, which must be accountable for the health impacts of their products.”

SOURCE:

The study was published on February 29, 2024, in The Lancet. The study was conducted by the NCD Risk Factor Collaboration and the WHO.

LIMITATIONS:

Data differences in countries included that some had limited data and three had none, requiring some estimates to be formed using data from other countries. Data availability was also lower among the youngest and oldest patients, increasing uncertainty of data in those age groups. In addition, data from health surveys can be subject to error, and BMI can be an imperfect measure of the extent or distribution of body fat.

DISCLOSURES:

The study was funded by UK Medical Research Council, UK Research and Innovation, and the European Commission.
 

A version of this article appeared on Medscape.com.

TOPLINE:

People with diabetes who live in small towns in the United States experience higher rates of complications than those living in cities and remote areas.

METHODOLOGY:

Retrospective cohort study using the OptumLabs Data Warehouse used a deidentified data set of US commercial and Medicare Advantage beneficiaries including 2,901,563 adults with diabetes between 2012 and 2021.

Overall, 2.6% lived in remote areas (population < 2500), 14.1% in small towns (2500-50,000), and 83.3% in cities (> 50,000).

Multivariable analysis adjusted for age, sex, health plan type, index year, diabetes type, baseline comorbidities, and medication use.

TAKEAWAY:

Relative to people living in cities, people in remote areas had significantly greater risks for myocardial infarction (hazard ratio, 1.06) and revascularization (1.04) but lower risks for hypoglycemia (0.90) and stroke (0.91).

Compared with cities, people living in small towns had significantly more hyperglycemia (1.06), hypoglycemia (1.15), end-stage kidney disease (1.04), myocardial infarction (1.10), heart failure (1.05), amputation (1.05), other lower-extremity complications (1.02), and revascularization (1.05), but a lower risk for stroke (0.95).

Compared with small towns, people living in remote areas had lower risks for hyperglycemia (0.85), hypoglycemia (0.92), and heart failure (0.94).

No geographic differences were found for retinopathy or atrial fibrillation/flutter.

The results didn’t differ significantly when the 2.5% overall with type 1 diabetes were removed from the dataset.

IN PRACTICE:

“While more research is needed to better understand the underlying causes of disparate diabetes outcomes along the rural-urban continuum, this study establishes the foundational differences to guide improvement efforts and helps to identify complications with the greatest disparities to which policy interventions may be targeted.”

SOURCE:

The study was conducted by Kyle Steiger, MD, Internal Medicine Residency, Mayo Clinic, Rochester, Minnesota, and colleagues, and published February 22 in Diabetes Care.

LIMITATIONS:

Claims data were from a single national health insurance provider that administers multiple private and Medicare Advantage health plans with disproportionate representation of urban populations and without people who have Medicaid or traditional Medicare fee-for-service or who are without insurance (and would be expected to have higher complication rates). There were no data on race/ethnicity. Potential for residual confounding.

DISCLOSURES:

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Steiger had no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

People with diabetes who live in small towns in the United States experience higher rates of complications than those living in cities and remote areas.

METHODOLOGY:

Retrospective cohort study using the OptumLabs Data Warehouse used a deidentified data set of US commercial and Medicare Advantage beneficiaries including 2,901,563 adults with diabetes between 2012 and 2021.

Overall, 2.6% lived in remote areas (population < 2500), 14.1% in small towns (2500-50,000), and 83.3% in cities (> 50,000).

Multivariable analysis adjusted for age, sex, health plan type, index year, diabetes type, baseline comorbidities, and medication use.

TAKEAWAY:

Relative to people living in cities, people in remote areas had significantly greater risks for myocardial infarction (hazard ratio, 1.06) and revascularization (1.04) but lower risks for hypoglycemia (0.90) and stroke (0.91).

Compared with cities, people living in small towns had significantly more hyperglycemia (1.06), hypoglycemia (1.15), end-stage kidney disease (1.04), myocardial infarction (1.10), heart failure (1.05), amputation (1.05), other lower-extremity complications (1.02), and revascularization (1.05), but a lower risk for stroke (0.95).

Compared with small towns, people living in remote areas had lower risks for hyperglycemia (0.85), hypoglycemia (0.92), and heart failure (0.94).

No geographic differences were found for retinopathy or atrial fibrillation/flutter.

The results didn’t differ significantly when the 2.5% overall with type 1 diabetes were removed from the dataset.

IN PRACTICE:

“While more research is needed to better understand the underlying causes of disparate diabetes outcomes along the rural-urban continuum, this study establishes the foundational differences to guide improvement efforts and helps to identify complications with the greatest disparities to which policy interventions may be targeted.”

SOURCE:

The study was conducted by Kyle Steiger, MD, Internal Medicine Residency, Mayo Clinic, Rochester, Minnesota, and colleagues, and published February 22 in Diabetes Care.

LIMITATIONS:

Claims data were from a single national health insurance provider that administers multiple private and Medicare Advantage health plans with disproportionate representation of urban populations and without people who have Medicaid or traditional Medicare fee-for-service or who are without insurance (and would be expected to have higher complication rates). There were no data on race/ethnicity. Potential for residual confounding.

DISCLOSURES:

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Steiger had no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

People with diabetes who live in small towns in the United States experience higher rates of complications than those living in cities and remote areas.

METHODOLOGY:

Retrospective cohort study using the OptumLabs Data Warehouse used a deidentified data set of US commercial and Medicare Advantage beneficiaries including 2,901,563 adults with diabetes between 2012 and 2021.

Overall, 2.6% lived in remote areas (population < 2500), 14.1% in small towns (2500-50,000), and 83.3% in cities (> 50,000).

Multivariable analysis adjusted for age, sex, health plan type, index year, diabetes type, baseline comorbidities, and medication use.

TAKEAWAY:

Relative to people living in cities, people in remote areas had significantly greater risks for myocardial infarction (hazard ratio, 1.06) and revascularization (1.04) but lower risks for hypoglycemia (0.90) and stroke (0.91).

Compared with cities, people living in small towns had significantly more hyperglycemia (1.06), hypoglycemia (1.15), end-stage kidney disease (1.04), myocardial infarction (1.10), heart failure (1.05), amputation (1.05), other lower-extremity complications (1.02), and revascularization (1.05), but a lower risk for stroke (0.95).

Compared with small towns, people living in remote areas had lower risks for hyperglycemia (0.85), hypoglycemia (0.92), and heart failure (0.94).

No geographic differences were found for retinopathy or atrial fibrillation/flutter.

The results didn’t differ significantly when the 2.5% overall with type 1 diabetes were removed from the dataset.

IN PRACTICE:

“While more research is needed to better understand the underlying causes of disparate diabetes outcomes along the rural-urban continuum, this study establishes the foundational differences to guide improvement efforts and helps to identify complications with the greatest disparities to which policy interventions may be targeted.”

SOURCE:

The study was conducted by Kyle Steiger, MD, Internal Medicine Residency, Mayo Clinic, Rochester, Minnesota, and colleagues, and published February 22 in Diabetes Care.

LIMITATIONS:

Claims data were from a single national health insurance provider that administers multiple private and Medicare Advantage health plans with disproportionate representation of urban populations and without people who have Medicaid or traditional Medicare fee-for-service or who are without insurance (and would be expected to have higher complication rates). There were no data on race/ethnicity. Potential for residual confounding.

DISCLOSURES:

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Steiger had no disclosures.
 

A version of this article appeared on Medscape.com.

A significant quantity of dysfunctional monocytes appears to indicate poor cardiovascular prognosis in patients with type 2 diabetes, according to a new publication. Nicolas Venteclef, PhD, director of an Inserm institute for diabetes research at Necker Enfants Malades Hospital in Paris, France, led the research.

Quantifying Inflammation

Patients with type 2 diabetes have about twice the risk for a cardiovascular event associated with atherosclerosis, such as a heart attack or stroke, during their lifetimes. “Predicting these complications in diabetic patients is usually very difficult,” Dr. Venteclef told this news organization.

“They are strongly associated with inflammation in these patients. Therefore, we sought to quantify this inflammation in the blood.” To do this, his team focused on monocytes, a category of white blood cells circulating in the blood. They measured the blood concentration of monocytes and the subtypes present in patients with type 2 diabetes.

The results were published in Circulation Research.
 

Dysfunctional Monocytes

The team worked with three cohorts of patients. The first, named AngioSafe-2, consisting of 672 patients with type 2 diabetes, was recruited from the diabetology departments of Lariboisière and Bichat Claude Bernard hospitals in France. This cohort allowed researchers to demonstrate that the higher the number of circulating monocytes, the greater the risk for cardiovascular events, independent of age and duration of diabetes. This observation was confirmed through a second cohort, GLUTADIAB, that comprised 279 patients with type 2 diabetes. Scientists complemented their work with molecular analysis of circulating monocytes in these two cohorts, which revealed certain predominant monocyte subtypes in patients with type 2 diabetes at high cardiovascular risk. “These monocytes are dysfunctional because they have a mitochondrial problem,” Dr. Venteclef explained.

To better understand how these results could be used to predict cardiovascular risk, the team collaborated with colleagues from the University Hospital of Nantes on a cohort called SURDIAGENE, which included 757 patients with type 2 diabetes. “We conducted a longitudinal study by following these patients for 10 years and quantifying cardiovascular events and deaths,” said Dr. Venteclef. Circulating monocyte levels were correlated with the occurrence of heart attacks or strokes. The researchers observed that patients with type 2 diabetes with a monocyte count above a certain threshold (0.5 × 109/L) had a five- to seven-times higher risk for cardiovascular events over 10 years than those with a monocyte count below this threshold.

A patent was filed at the end of 2023 to protect this discovery. “Our next step is to develop a sensor to quantify monocytes more easily and avoid blood draws,” said Dr. Venteclef. “As part of a European project, we will also launch a trial with an anti-inflammatory drug in diabetics, with the hope of interrupting the inflammatory trajectory and preventing complications.”
 

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

A significant quantity of dysfunctional monocytes appears to indicate poor cardiovascular prognosis in patients with type 2 diabetes, according to a new publication. Nicolas Venteclef, PhD, director of an Inserm institute for diabetes research at Necker Enfants Malades Hospital in Paris, France, led the research.

Quantifying Inflammation

Patients with type 2 diabetes have about twice the risk for a cardiovascular event associated with atherosclerosis, such as a heart attack or stroke, during their lifetimes. “Predicting these complications in diabetic patients is usually very difficult,” Dr. Venteclef told this news organization.

“They are strongly associated with inflammation in these patients. Therefore, we sought to quantify this inflammation in the blood.” To do this, his team focused on monocytes, a category of white blood cells circulating in the blood. They measured the blood concentration of monocytes and the subtypes present in patients with type 2 diabetes.

The results were published in Circulation Research.
 

Dysfunctional Monocytes

The team worked with three cohorts of patients. The first, named AngioSafe-2, consisting of 672 patients with type 2 diabetes, was recruited from the diabetology departments of Lariboisière and Bichat Claude Bernard hospitals in France. This cohort allowed researchers to demonstrate that the higher the number of circulating monocytes, the greater the risk for cardiovascular events, independent of age and duration of diabetes. This observation was confirmed through a second cohort, GLUTADIAB, that comprised 279 patients with type 2 diabetes. Scientists complemented their work with molecular analysis of circulating monocytes in these two cohorts, which revealed certain predominant monocyte subtypes in patients with type 2 diabetes at high cardiovascular risk. “These monocytes are dysfunctional because they have a mitochondrial problem,” Dr. Venteclef explained.

To better understand how these results could be used to predict cardiovascular risk, the team collaborated with colleagues from the University Hospital of Nantes on a cohort called SURDIAGENE, which included 757 patients with type 2 diabetes. “We conducted a longitudinal study by following these patients for 10 years and quantifying cardiovascular events and deaths,” said Dr. Venteclef. Circulating monocyte levels were correlated with the occurrence of heart attacks or strokes. The researchers observed that patients with type 2 diabetes with a monocyte count above a certain threshold (0.5 × 109/L) had a five- to seven-times higher risk for cardiovascular events over 10 years than those with a monocyte count below this threshold.

A patent was filed at the end of 2023 to protect this discovery. “Our next step is to develop a sensor to quantify monocytes more easily and avoid blood draws,” said Dr. Venteclef. “As part of a European project, we will also launch a trial with an anti-inflammatory drug in diabetics, with the hope of interrupting the inflammatory trajectory and preventing complications.”
 

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

A significant quantity of dysfunctional monocytes appears to indicate poor cardiovascular prognosis in patients with type 2 diabetes, according to a new publication. Nicolas Venteclef, PhD, director of an Inserm institute for diabetes research at Necker Enfants Malades Hospital in Paris, France, led the research.

Quantifying Inflammation

Patients with type 2 diabetes have about twice the risk for a cardiovascular event associated with atherosclerosis, such as a heart attack or stroke, during their lifetimes. “Predicting these complications in diabetic patients is usually very difficult,” Dr. Venteclef told this news organization.

“They are strongly associated with inflammation in these patients. Therefore, we sought to quantify this inflammation in the blood.” To do this, his team focused on monocytes, a category of white blood cells circulating in the blood. They measured the blood concentration of monocytes and the subtypes present in patients with type 2 diabetes.

The results were published in Circulation Research.
 

Dysfunctional Monocytes

The team worked with three cohorts of patients. The first, named AngioSafe-2, consisting of 672 patients with type 2 diabetes, was recruited from the diabetology departments of Lariboisière and Bichat Claude Bernard hospitals in France. This cohort allowed researchers to demonstrate that the higher the number of circulating monocytes, the greater the risk for cardiovascular events, independent of age and duration of diabetes. This observation was confirmed through a second cohort, GLUTADIAB, that comprised 279 patients with type 2 diabetes. Scientists complemented their work with molecular analysis of circulating monocytes in these two cohorts, which revealed certain predominant monocyte subtypes in patients with type 2 diabetes at high cardiovascular risk. “These monocytes are dysfunctional because they have a mitochondrial problem,” Dr. Venteclef explained.

To better understand how these results could be used to predict cardiovascular risk, the team collaborated with colleagues from the University Hospital of Nantes on a cohort called SURDIAGENE, which included 757 patients with type 2 diabetes. “We conducted a longitudinal study by following these patients for 10 years and quantifying cardiovascular events and deaths,” said Dr. Venteclef. Circulating monocyte levels were correlated with the occurrence of heart attacks or strokes. The researchers observed that patients with type 2 diabetes with a monocyte count above a certain threshold (0.5 × 109/L) had a five- to seven-times higher risk for cardiovascular events over 10 years than those with a monocyte count below this threshold.

A patent was filed at the end of 2023 to protect this discovery. “Our next step is to develop a sensor to quantify monocytes more easily and avoid blood draws,” said Dr. Venteclef. “As part of a European project, we will also launch a trial with an anti-inflammatory drug in diabetics, with the hope of interrupting the inflammatory trajectory and preventing complications.”
 

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

TOPLINE:

Greater adherence to a plant-based dietary pattern was associated with a lower risk of developing type 2 diabetes (T2D) among middle-aged US adults. Greater intake of healthful plant foods, rather than lower intake of non-red meat animal foods, was the main factor underlying the inverse associations.

METHODOLOGY:

• The study population was 11,965 adults aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study who didn›t have diabetes at baseline and who completed food-frequency questionnaires.
• Plant-based diet adherence was classified overall with the plant-based diet index (PDI) and also with higher healthful PDI (hPDI) and higher unhealthful PDI (uPDI) indexes.

TAKEAWAY:

• Mean daily total plant and animal food intakes for the highest quintile (5) were 15.1 and 3.4 servings per day, respectively, whereas average consumption for the lowest quintile (1) was 9.9 and 5.8 servings per day, respectively.
• During a median 22 years’ follow-up, 35% (n = 4208) of the participants developed T2D.
• After controlling for age, sex, race center, energy intake, education, income, smoking, alcohol intake, physical activity, and margarine intake, those in PDI quintile 5 had a significantly lower risk of developing T2D than in quintile 1 (hazard ratio, 0.89; P = .01).
• As a continuous score, each 10-point higher PDI score was associated with a significant 6% lower risk for T2D (P = .01).
• Higher hPDI scores were also inversely associated with T2D risk (hazard ratio, 0.85 for quintiles 5 vs 1; P < .001), and (0.90 per each 10 units higher; P < .001).
• Higher uPDI scores were not significantly associated with diabetes risk, regardless of adjustments (P > .05).
• Associations between plant-based diet scores and diabetes did not differ by sex, age, race, or body mass index (BMI) after accounting for multiple comparisons (all P interaction > .05).
• Further adjustment for BMI attenuated the associations between overall and healthy plant-based diets and diabetes risk, suggesting that lower adiposity may partly explain the favorable association.

IN PRACTICE:

“Emphasizing plant foods may be an effective dietary strategy to delay or prevent the onset of diabetes.”

SOURCE:

The study conducted by Valerie K. Sullivan, PhD, RD, of the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, and colleagues was published online in Diabetes Care.

LIMITATIONS:

The limitations were self-reported dietary intake, diets assessed decades ago, possible food misclassification, possible selection bias, and residual confounding.

DISCLOSURES:

The ARIC study was funded by the US National Institutes of Health. The authors had no further disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Greater adherence to a plant-based dietary pattern was associated with a lower risk of developing type 2 diabetes (T2D) among middle-aged US adults. Greater intake of healthful plant foods, rather than lower intake of non-red meat animal foods, was the main factor underlying the inverse associations.

METHODOLOGY:

• The study population was 11,965 adults aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study who didn›t have diabetes at baseline and who completed food-frequency questionnaires.
• Plant-based diet adherence was classified overall with the plant-based diet index (PDI) and also with higher healthful PDI (hPDI) and higher unhealthful PDI (uPDI) indexes.

TAKEAWAY:

• Mean daily total plant and animal food intakes for the highest quintile (5) were 15.1 and 3.4 servings per day, respectively, whereas average consumption for the lowest quintile (1) was 9.9 and 5.8 servings per day, respectively.
• During a median 22 years’ follow-up, 35% (n = 4208) of the participants developed T2D.
• After controlling for age, sex, race center, energy intake, education, income, smoking, alcohol intake, physical activity, and margarine intake, those in PDI quintile 5 had a significantly lower risk of developing T2D than in quintile 1 (hazard ratio, 0.89; P = .01).
• As a continuous score, each 10-point higher PDI score was associated with a significant 6% lower risk for T2D (P = .01).
• Higher hPDI scores were also inversely associated with T2D risk (hazard ratio, 0.85 for quintiles 5 vs 1; P < .001), and (0.90 per each 10 units higher; P < .001).
• Higher uPDI scores were not significantly associated with diabetes risk, regardless of adjustments (P > .05).
• Associations between plant-based diet scores and diabetes did not differ by sex, age, race, or body mass index (BMI) after accounting for multiple comparisons (all P interaction > .05).
• Further adjustment for BMI attenuated the associations between overall and healthy plant-based diets and diabetes risk, suggesting that lower adiposity may partly explain the favorable association.

IN PRACTICE:

“Emphasizing plant foods may be an effective dietary strategy to delay or prevent the onset of diabetes.”

SOURCE:

The study conducted by Valerie K. Sullivan, PhD, RD, of the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, and colleagues was published online in Diabetes Care.

LIMITATIONS:

The limitations were self-reported dietary intake, diets assessed decades ago, possible food misclassification, possible selection bias, and residual confounding.

DISCLOSURES:

The ARIC study was funded by the US National Institutes of Health. The authors had no further disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Greater adherence to a plant-based dietary pattern was associated with a lower risk of developing type 2 diabetes (T2D) among middle-aged US adults. Greater intake of healthful plant foods, rather than lower intake of non-red meat animal foods, was the main factor underlying the inverse associations.

METHODOLOGY:

• The study population was 11,965 adults aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study who didn›t have diabetes at baseline and who completed food-frequency questionnaires.
• Plant-based diet adherence was classified overall with the plant-based diet index (PDI) and also with higher healthful PDI (hPDI) and higher unhealthful PDI (uPDI) indexes.

TAKEAWAY:

• Mean daily total plant and animal food intakes for the highest quintile (5) were 15.1 and 3.4 servings per day, respectively, whereas average consumption for the lowest quintile (1) was 9.9 and 5.8 servings per day, respectively.
• During a median 22 years’ follow-up, 35% (n = 4208) of the participants developed T2D.
• After controlling for age, sex, race center, energy intake, education, income, smoking, alcohol intake, physical activity, and margarine intake, those in PDI quintile 5 had a significantly lower risk of developing T2D than in quintile 1 (hazard ratio, 0.89; P = .01).
• As a continuous score, each 10-point higher PDI score was associated with a significant 6% lower risk for T2D (P = .01).
• Higher hPDI scores were also inversely associated with T2D risk (hazard ratio, 0.85 for quintiles 5 vs 1; P < .001), and (0.90 per each 10 units higher; P < .001).
• Higher uPDI scores were not significantly associated with diabetes risk, regardless of adjustments (P > .05).
• Associations between plant-based diet scores and diabetes did not differ by sex, age, race, or body mass index (BMI) after accounting for multiple comparisons (all P interaction > .05).
• Further adjustment for BMI attenuated the associations between overall and healthy plant-based diets and diabetes risk, suggesting that lower adiposity may partly explain the favorable association.

IN PRACTICE:

“Emphasizing plant foods may be an effective dietary strategy to delay or prevent the onset of diabetes.”

SOURCE:

The study conducted by Valerie K. Sullivan, PhD, RD, of the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, and colleagues was published online in Diabetes Care.

LIMITATIONS:

The limitations were self-reported dietary intake, diets assessed decades ago, possible food misclassification, possible selection bias, and residual confounding.

DISCLOSURES:

The ARIC study was funded by the US National Institutes of Health. The authors had no further disclosures.

A version of this article appeared on Medscape.com.