Diabetes

In a large cohort of older adults with type 2 diabetes in Italy, those with the highest intake of ultraprocessed food and beverages (UPF) were more likely to die of all causes or cardiovascular disease (CVD) within a decade than those with the lowest intake – independent of adherence to a healthy Mediterranean diet.

Adults in the top quartile of UPF intake had a 64% increased risk of all-cause death and a 2.5-fold increased risk of CVD death during follow-up, compared with those in the lowest quartile, after adjusting for variables including Mediterranean diet score.

These findings from the Moli-sani study by Marialaura Bonaccio, PhD, from the Institute for Research, Hospitalization and Healthcare (IRCCS) Neuromed, in Pozzilli, Italy, and colleagues, were published online in the American Journal of Clinical Nutrition.

“Dietary recommendations for prevention and management of type 2 diabetes almost exclusively prioritize consumption of nutritionally balanced foods that are the source of fiber [and] healthy fats and [are] poor in free sugars, and promote dietary patterns – such as the Mediterranean diet and the DASH diet – that place a large emphasis on food groups (for example, whole grains, legumes, nuts, fruits, and vegetables) regardless of food processing,” the researchers note.

The research suggests that “besides prioritizing the adoption of a diet based on nutritional requirements, dietary guidelines for the management of type 2 diabetes should also recommend limiting UPF,” they conclude.

“In addition to the adoption of a diet based on well-known nutritional requirements, dietary recommendations should also suggest limiting the consumption of ultraprocessed foods as much as possible,” Giovanni de Gaetano, MD, PhD, president, IRCCS Neuromed, echoed, in a press release from the institute.

“In this context, and not only for people with diabetes, the front-of-pack nutrition labels should also include information on the degree of food processing,” he observed.

Caroline M. Apovian, MD, who was not involved with the study, agrees that it is wise to limit consumption of UPF.

However, we need more research to better understand which components of UPF are harmful and the biologic mechanisms, Dr. Apovian, who is codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, and a professor of medicine at Harvard Medical School, both in Boston, told this news organization in an interview.

She noted that in a randomized crossover trial in 20 patients who were instructed to eat as much or as little as they wanted, people ate more and gained weight during 2 weeks of a diet high in UPF, compared with 2 weeks of an unprocessed diet matched for presented calories, carbohydrate, sugar, fat, sodium, and fiber.
 

Ultraprocessed foods classed according to Nova system

UPF is “made mostly or entirely from substances derived from foods and additives, using a series of processes and containing minimal whole foods,” and they “are usually nutrient-poor, high in calories, added sugar, sodium, and unhealthy fats,” the Italian researchers write.

High intake of UPF, they add, may exacerbate health risks in people with type 2 diabetes, who are already at higher risk of premature mortality, mainly due to diabetes-related complications.

The researchers analyzed data from a subset of patients in the Moli-sani study of environmental and genetic factors underlying disease, which enrolled 24,325 individuals aged 35 and older who lived in Molise, in central-southern Italy, in 2005-2010.

The current analysis included 1,065 participants in Moli-sani who had type 2 diabetes at baseline and completed a food frequency questionnaire by which participants reported their consumption of 188 foods and beverages in the previous 12 months.

Participants were a mean age of 65 years, and 60% were men.

Most UPF intake was from processed meat (22.4%), crispbread/rusks (16.6%), nonhomemade pizza (11.2%), and cakes, pies, pastries, and puddings (8.8%).

Researchers categorized foods and beverages into four groups with increasing degrees of processing, based on the Nova Food Classification System:

• Group 1: Fresh or minimally processed foods and beverages (for example, fruit, meat, milk).
• Group 2: Processed culinary ingredients (for example, oils, butter).
• Group 3: Processed foods and beverages (for example, canned fish, bread).
• Group 4: UPF (22 foods and beverages including carbonated drinks, processed meats, sweet or savory packaged snacks, margarine, and foods and beverages with artificial sweeteners).

Participants were divided into four quartiles based on UPF consumption.

The mean percentage of UPF consumption out of total food and beverage intake was 2.8%, 5.2%, 7.7%, and 14.4% for quartiles 1, 2, 3, and 4, respectively. By sex, these rates for quartile 1 were < 4.7% for women and < 3.7% for men, and for quartile 4 were ≥ 10.5% for women and ≥ 9% for men.

Participants with the highest UPF intake were younger (mean age, 63 vs. 67 years) but otherwise had similar characteristics as other participants.

During a median follow-up of 11.6 years, 308 participants died from all causes, including 129 who died from CVD.

Compared with participants with the lowest intake of UPF (quartile 1), those with the highest intake (quartile 4) had a higher risk of all-cause mortality (hazard ratio, 1.70) and CVD mortality (HR, 2.64) during follow-up, after multivariable adjustment. The analysis adjusted for sex, age, energy intake, residence, education, housing, smoking, body mass index, leisure-time physical activity, history of cancer or cardiovascular disease, hypertension, hyperlipidemia, aspirin use, years since type 2 diabetes diagnosis, and special diet for blood glucose control.

After further adjusting for Mediterranean diet score, the risk of all-cause and CVD mortality during follow-up for patients with the highest versus lowest intake of UPF remained similar (HR, 1.64 and 2.55, respectively).

There was a linear dose–response relationship between UPF and all-cause and CVD mortality.

Increasing intake of fruit drinks, carbonated drinks, and salty biscuits was associated with higher all-cause and CVD mortality rates, and consumption of stock cubes and margarine was further related to higher CVD death.

The researchers acknowledge that the study was observational, and therefore cannot determine cause and effect, and was not designed to specifically collect dietary data according to the Nova classification. The findings may not be generalizable to other populations.

The analysis was partly funded by grants from the AIRC and Italian Ministry of Health. The authors have reported no relevant financial relationships.

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

In a large cohort of older adults with type 2 diabetes in Italy, those with the highest intake of ultraprocessed food and beverages (UPF) were more likely to die of all causes or cardiovascular disease (CVD) within a decade than those with the lowest intake – independent of adherence to a healthy Mediterranean diet.

Adults in the top quartile of UPF intake had a 64% increased risk of all-cause death and a 2.5-fold increased risk of CVD death during follow-up, compared with those in the lowest quartile, after adjusting for variables including Mediterranean diet score.

These findings from the Moli-sani study by Marialaura Bonaccio, PhD, from the Institute for Research, Hospitalization and Healthcare (IRCCS) Neuromed, in Pozzilli, Italy, and colleagues, were published online in the American Journal of Clinical Nutrition.

“Dietary recommendations for prevention and management of type 2 diabetes almost exclusively prioritize consumption of nutritionally balanced foods that are the source of fiber [and] healthy fats and [are] poor in free sugars, and promote dietary patterns – such as the Mediterranean diet and the DASH diet – that place a large emphasis on food groups (for example, whole grains, legumes, nuts, fruits, and vegetables) regardless of food processing,” the researchers note.

The research suggests that “besides prioritizing the adoption of a diet based on nutritional requirements, dietary guidelines for the management of type 2 diabetes should also recommend limiting UPF,” they conclude.

“In addition to the adoption of a diet based on well-known nutritional requirements, dietary recommendations should also suggest limiting the consumption of ultraprocessed foods as much as possible,” Giovanni de Gaetano, MD, PhD, president, IRCCS Neuromed, echoed, in a press release from the institute.

“In this context, and not only for people with diabetes, the front-of-pack nutrition labels should also include information on the degree of food processing,” he observed.

Caroline M. Apovian, MD, who was not involved with the study, agrees that it is wise to limit consumption of UPF.

However, we need more research to better understand which components of UPF are harmful and the biologic mechanisms, Dr. Apovian, who is codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, and a professor of medicine at Harvard Medical School, both in Boston, told this news organization in an interview.

She noted that in a randomized crossover trial in 20 patients who were instructed to eat as much or as little as they wanted, people ate more and gained weight during 2 weeks of a diet high in UPF, compared with 2 weeks of an unprocessed diet matched for presented calories, carbohydrate, sugar, fat, sodium, and fiber.
 

Ultraprocessed foods classed according to Nova system

UPF is “made mostly or entirely from substances derived from foods and additives, using a series of processes and containing minimal whole foods,” and they “are usually nutrient-poor, high in calories, added sugar, sodium, and unhealthy fats,” the Italian researchers write.

High intake of UPF, they add, may exacerbate health risks in people with type 2 diabetes, who are already at higher risk of premature mortality, mainly due to diabetes-related complications.

The researchers analyzed data from a subset of patients in the Moli-sani study of environmental and genetic factors underlying disease, which enrolled 24,325 individuals aged 35 and older who lived in Molise, in central-southern Italy, in 2005-2010.

The current analysis included 1,065 participants in Moli-sani who had type 2 diabetes at baseline and completed a food frequency questionnaire by which participants reported their consumption of 188 foods and beverages in the previous 12 months.

Participants were a mean age of 65 years, and 60% were men.

Most UPF intake was from processed meat (22.4%), crispbread/rusks (16.6%), nonhomemade pizza (11.2%), and cakes, pies, pastries, and puddings (8.8%).

Researchers categorized foods and beverages into four groups with increasing degrees of processing, based on the Nova Food Classification System:

• Group 1: Fresh or minimally processed foods and beverages (for example, fruit, meat, milk).
• Group 2: Processed culinary ingredients (for example, oils, butter).
• Group 3: Processed foods and beverages (for example, canned fish, bread).
• Group 4: UPF (22 foods and beverages including carbonated drinks, processed meats, sweet or savory packaged snacks, margarine, and foods and beverages with artificial sweeteners).

Participants were divided into four quartiles based on UPF consumption.

The mean percentage of UPF consumption out of total food and beverage intake was 2.8%, 5.2%, 7.7%, and 14.4% for quartiles 1, 2, 3, and 4, respectively. By sex, these rates for quartile 1 were < 4.7% for women and < 3.7% for men, and for quartile 4 were ≥ 10.5% for women and ≥ 9% for men.

Participants with the highest UPF intake were younger (mean age, 63 vs. 67 years) but otherwise had similar characteristics as other participants.

During a median follow-up of 11.6 years, 308 participants died from all causes, including 129 who died from CVD.

Compared with participants with the lowest intake of UPF (quartile 1), those with the highest intake (quartile 4) had a higher risk of all-cause mortality (hazard ratio, 1.70) and CVD mortality (HR, 2.64) during follow-up, after multivariable adjustment. The analysis adjusted for sex, age, energy intake, residence, education, housing, smoking, body mass index, leisure-time physical activity, history of cancer or cardiovascular disease, hypertension, hyperlipidemia, aspirin use, years since type 2 diabetes diagnosis, and special diet for blood glucose control.

After further adjusting for Mediterranean diet score, the risk of all-cause and CVD mortality during follow-up for patients with the highest versus lowest intake of UPF remained similar (HR, 1.64 and 2.55, respectively).

There was a linear dose–response relationship between UPF and all-cause and CVD mortality.

Increasing intake of fruit drinks, carbonated drinks, and salty biscuits was associated with higher all-cause and CVD mortality rates, and consumption of stock cubes and margarine was further related to higher CVD death.

The researchers acknowledge that the study was observational, and therefore cannot determine cause and effect, and was not designed to specifically collect dietary data according to the Nova classification. The findings may not be generalizable to other populations.

The analysis was partly funded by grants from the AIRC and Italian Ministry of Health. The authors have reported no relevant financial relationships.

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

In a large cohort of older adults with type 2 diabetes in Italy, those with the highest intake of ultraprocessed food and beverages (UPF) were more likely to die of all causes or cardiovascular disease (CVD) within a decade than those with the lowest intake – independent of adherence to a healthy Mediterranean diet.

Adults in the top quartile of UPF intake had a 64% increased risk of all-cause death and a 2.5-fold increased risk of CVD death during follow-up, compared with those in the lowest quartile, after adjusting for variables including Mediterranean diet score.

These findings from the Moli-sani study by Marialaura Bonaccio, PhD, from the Institute for Research, Hospitalization and Healthcare (IRCCS) Neuromed, in Pozzilli, Italy, and colleagues, were published online in the American Journal of Clinical Nutrition.

“Dietary recommendations for prevention and management of type 2 diabetes almost exclusively prioritize consumption of nutritionally balanced foods that are the source of fiber [and] healthy fats and [are] poor in free sugars, and promote dietary patterns – such as the Mediterranean diet and the DASH diet – that place a large emphasis on food groups (for example, whole grains, legumes, nuts, fruits, and vegetables) regardless of food processing,” the researchers note.

The research suggests that “besides prioritizing the adoption of a diet based on nutritional requirements, dietary guidelines for the management of type 2 diabetes should also recommend limiting UPF,” they conclude.

“In addition to the adoption of a diet based on well-known nutritional requirements, dietary recommendations should also suggest limiting the consumption of ultraprocessed foods as much as possible,” Giovanni de Gaetano, MD, PhD, president, IRCCS Neuromed, echoed, in a press release from the institute.

“In this context, and not only for people with diabetes, the front-of-pack nutrition labels should also include information on the degree of food processing,” he observed.

Caroline M. Apovian, MD, who was not involved with the study, agrees that it is wise to limit consumption of UPF.

However, we need more research to better understand which components of UPF are harmful and the biologic mechanisms, Dr. Apovian, who is codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, and a professor of medicine at Harvard Medical School, both in Boston, told this news organization in an interview.

She noted that in a randomized crossover trial in 20 patients who were instructed to eat as much or as little as they wanted, people ate more and gained weight during 2 weeks of a diet high in UPF, compared with 2 weeks of an unprocessed diet matched for presented calories, carbohydrate, sugar, fat, sodium, and fiber.
 

Ultraprocessed foods classed according to Nova system

UPF is “made mostly or entirely from substances derived from foods and additives, using a series of processes and containing minimal whole foods,” and they “are usually nutrient-poor, high in calories, added sugar, sodium, and unhealthy fats,” the Italian researchers write.

High intake of UPF, they add, may exacerbate health risks in people with type 2 diabetes, who are already at higher risk of premature mortality, mainly due to diabetes-related complications.

The researchers analyzed data from a subset of patients in the Moli-sani study of environmental and genetic factors underlying disease, which enrolled 24,325 individuals aged 35 and older who lived in Molise, in central-southern Italy, in 2005-2010.

The current analysis included 1,065 participants in Moli-sani who had type 2 diabetes at baseline and completed a food frequency questionnaire by which participants reported their consumption of 188 foods and beverages in the previous 12 months.

Participants were a mean age of 65 years, and 60% were men.

Most UPF intake was from processed meat (22.4%), crispbread/rusks (16.6%), nonhomemade pizza (11.2%), and cakes, pies, pastries, and puddings (8.8%).

Researchers categorized foods and beverages into four groups with increasing degrees of processing, based on the Nova Food Classification System:

• Group 1: Fresh or minimally processed foods and beverages (for example, fruit, meat, milk).
• Group 2: Processed culinary ingredients (for example, oils, butter).
• Group 3: Processed foods and beverages (for example, canned fish, bread).
• Group 4: UPF (22 foods and beverages including carbonated drinks, processed meats, sweet or savory packaged snacks, margarine, and foods and beverages with artificial sweeteners).

Participants were divided into four quartiles based on UPF consumption.

The mean percentage of UPF consumption out of total food and beverage intake was 2.8%, 5.2%, 7.7%, and 14.4% for quartiles 1, 2, 3, and 4, respectively. By sex, these rates for quartile 1 were < 4.7% for women and < 3.7% for men, and for quartile 4 were ≥ 10.5% for women and ≥ 9% for men.

Participants with the highest UPF intake were younger (mean age, 63 vs. 67 years) but otherwise had similar characteristics as other participants.

During a median follow-up of 11.6 years, 308 participants died from all causes, including 129 who died from CVD.

Compared with participants with the lowest intake of UPF (quartile 1), those with the highest intake (quartile 4) had a higher risk of all-cause mortality (hazard ratio, 1.70) and CVD mortality (HR, 2.64) during follow-up, after multivariable adjustment. The analysis adjusted for sex, age, energy intake, residence, education, housing, smoking, body mass index, leisure-time physical activity, history of cancer or cardiovascular disease, hypertension, hyperlipidemia, aspirin use, years since type 2 diabetes diagnosis, and special diet for blood glucose control.

After further adjusting for Mediterranean diet score, the risk of all-cause and CVD mortality during follow-up for patients with the highest versus lowest intake of UPF remained similar (HR, 1.64 and 2.55, respectively).

There was a linear dose–response relationship between UPF and all-cause and CVD mortality.

Increasing intake of fruit drinks, carbonated drinks, and salty biscuits was associated with higher all-cause and CVD mortality rates, and consumption of stock cubes and margarine was further related to higher CVD death.

The researchers acknowledge that the study was observational, and therefore cannot determine cause and effect, and was not designed to specifically collect dietary data according to the Nova classification. The findings may not be generalizable to other populations.

The analysis was partly funded by grants from the AIRC and Italian Ministry of Health. The authors have reported no relevant financial relationships.

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

As we navigate the ever-evolving landscape of diabetic foot disease management, I’d like to discuss the updated 2023 International Working Group on the Diabetic Foot guidelines and their implications for our practice. The goal is to create a common language of risk that is easily related from clinician to clinician to patient.

Whatever language we use, though, the problem we face is vast:

• Diabetic foot ulcers affect approximately 18.6 million people worldwide and 1.6 million in the United States each year.
• They are associated with high rates of premature death, with a 5-year mortality rate of 30%. This rate is greater than 70% for those with above-foot amputations, worse than all but the most aggressive cancers.
• The direct costs of treating diabetic foot ulcers in the United States is estimated at $9 billion-$13 billion annually.
• Over 550 million people worldwide have diabetes, with 18.6 million developing foot ulcers annually. Up to 34% of those with diabetes will develop a foot ulcer.
• About 20% of those with a diabetic foot ulcer will undergo amputation, a major cause of which is infection, which affects 50% of foot ulcers.
• Up to 20% of those with a foot ulcer require hospitalization, with 15%-20% undergoing amputation. Inequities exist in diabetes-related foot complications:
• –Rates of major amputation are higher in non-Hispanic Black, Hispanic, and Native American populations, compared with non-Hispanic White populations.
• –Non-Hispanic Black and Hispanic populations present with more advanced ulcers and peripheral artery disease, and are more likely to undergo amputation without revascularization attempt.

The IWGDF, a multidisciplinary team of international experts, has recently updated its guidelines. This team, comprising endocrinologists, internal medicine physicians, physiatrists, podiatrists, and vascular surgeons from across the globe, has worked tirelessly to provide us with a comprehensive guide to managing diabetes-related foot ulcers.

The updated guidelines address five critical clinical questions, each with up to 13 important outcomes. The systematic review that underpins these guidelines identified 149 eligible studies, assessing 28 different systems. This exhaustive research has led to the development of seven key recommendations that address the clinical questions and consider the existence of different clinical settings.

One of the significant updates in the 2023 guidelines is the recommendation of SINBAD – site, ischemia, neuropathy, bacterial infection, area, and depth – as the priority wound classification system for people with diabetes and a foot ulcer. This system is particularly useful for interprofessional communication, describing each composite variable, and conducting clinical audits using the full score. However, the guidelines also recommend the use of other, more specific assessment systems for infection and peripheral artery disease from the Infectious Diseases Society of America/IWGDF when resources and an appropriate level of expertise exist.

The introduction of the Wound, Ischemia and Foot Infection (WIfI) classification system in the guidelines is also a noteworthy development. This system is crucial in assessing perfusion and the likely benefit of revascularization in a person with diabetes and a foot ulcer. By assessing the level of wound ischemia and infection, we can make informed decisions about the need for vascular intervention, which can significantly affect the patient’s outcome. This can be done simply by classifying each of the three categories of wound, ischemia, or foot infection as none, mild, moderate, or severe. By simplifying the very dynamic comorbidities of tissue loss, ischemia, and infection into a usable and predictive scale, it helps us to communicate risk across disciplines. This has been found to be highly predictive of healing, amputation, and mortality.

We use WIfI every day across our system. An example might include a patient we recently treated:

A 76-year-old woman presented with a wound to her left foot. Her past medical history revealed type 2 diabetes, peripheral neuropathy, and documented peripheral artery disease with prior bilateral femoral-popliteal bypass conducted at an external facility. In addition to gangrenous changes to her fourth toe, she displayed erythema and lymphangitic streaking up her dorsal foot. While she was afebrile, her white cell count was 13,000/mcL. Radiographic examinations did not show signs of osteomyelitis. Noninvasive vascular evaluations revealed an ankle brachial index of 0.4 and a toe pressure of 10 mm Hg. An aortogram with a lower-extremity runoff arteriogram confirmed the obstruction of her left femoral-popliteal bypass.

Taking these results into account, her WIfI score was determined as: wound 2 (moderate), ischemia 3 (severe), foot infection 2 (moderate, no sepsis), translating to a clinical stage 4. This denotes a high risk for major amputation.

Following a team discussion, she was taken to the operating room for an initial debridement of her infection which consisted of a partial fourth ray resection to the level of the mid-metatarsal. Following control of the infection, she received a vascular assessment which ultimately constituted a femoral to distal anterior tibial bypass. Following both of these, she was discharged on a negative-pressure wound therapy device, receiving a split-thickness skin graft 4 weeks later.

The guidelines also emphasize the need for specific training, skills, and experience to ensure the accuracy of the recommended systems for characterizing foot ulcers. The person applying these systems should be appropriately trained and, according to their national or regional standards, should have the knowledge, expertise, and skills necessary to manage people with a diabetes-related foot ulcer.

As we continue to navigate the complexities of diabetes-related foot disease, these guidelines serve as a valuable compass, guiding our decisions and actions. They remind us of the importance of continuous learning, collaboration, and the application of evidence-based practice in our work.

I encourage you to delve into these guidelines. Let’s use them to improve our practice, enhance our communication, and, ultimately, provide better care for our patients.

Dr. Armstrong is professor of surgery, director of limb preservation, University of Southern California, Los Angeles. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

As we navigate the ever-evolving landscape of diabetic foot disease management, I’d like to discuss the updated 2023 International Working Group on the Diabetic Foot guidelines and their implications for our practice. The goal is to create a common language of risk that is easily related from clinician to clinician to patient.

Whatever language we use, though, the problem we face is vast:

• Diabetic foot ulcers affect approximately 18.6 million people worldwide and 1.6 million in the United States each year.
• They are associated with high rates of premature death, with a 5-year mortality rate of 30%. This rate is greater than 70% for those with above-foot amputations, worse than all but the most aggressive cancers.
• The direct costs of treating diabetic foot ulcers in the United States is estimated at $9 billion-$13 billion annually.
• Over 550 million people worldwide have diabetes, with 18.6 million developing foot ulcers annually. Up to 34% of those with diabetes will develop a foot ulcer.
• About 20% of those with a diabetic foot ulcer will undergo amputation, a major cause of which is infection, which affects 50% of foot ulcers.
• Up to 20% of those with a foot ulcer require hospitalization, with 15%-20% undergoing amputation. Inequities exist in diabetes-related foot complications:
• –Rates of major amputation are higher in non-Hispanic Black, Hispanic, and Native American populations, compared with non-Hispanic White populations.
• –Non-Hispanic Black and Hispanic populations present with more advanced ulcers and peripheral artery disease, and are more likely to undergo amputation without revascularization attempt.

The IWGDF, a multidisciplinary team of international experts, has recently updated its guidelines. This team, comprising endocrinologists, internal medicine physicians, physiatrists, podiatrists, and vascular surgeons from across the globe, has worked tirelessly to provide us with a comprehensive guide to managing diabetes-related foot ulcers.

The updated guidelines address five critical clinical questions, each with up to 13 important outcomes. The systematic review that underpins these guidelines identified 149 eligible studies, assessing 28 different systems. This exhaustive research has led to the development of seven key recommendations that address the clinical questions and consider the existence of different clinical settings.

One of the significant updates in the 2023 guidelines is the recommendation of SINBAD – site, ischemia, neuropathy, bacterial infection, area, and depth – as the priority wound classification system for people with diabetes and a foot ulcer. This system is particularly useful for interprofessional communication, describing each composite variable, and conducting clinical audits using the full score. However, the guidelines also recommend the use of other, more specific assessment systems for infection and peripheral artery disease from the Infectious Diseases Society of America/IWGDF when resources and an appropriate level of expertise exist.

The introduction of the Wound, Ischemia and Foot Infection (WIfI) classification system in the guidelines is also a noteworthy development. This system is crucial in assessing perfusion and the likely benefit of revascularization in a person with diabetes and a foot ulcer. By assessing the level of wound ischemia and infection, we can make informed decisions about the need for vascular intervention, which can significantly affect the patient’s outcome. This can be done simply by classifying each of the three categories of wound, ischemia, or foot infection as none, mild, moderate, or severe. By simplifying the very dynamic comorbidities of tissue loss, ischemia, and infection into a usable and predictive scale, it helps us to communicate risk across disciplines. This has been found to be highly predictive of healing, amputation, and mortality.

We use WIfI every day across our system. An example might include a patient we recently treated:

A 76-year-old woman presented with a wound to her left foot. Her past medical history revealed type 2 diabetes, peripheral neuropathy, and documented peripheral artery disease with prior bilateral femoral-popliteal bypass conducted at an external facility. In addition to gangrenous changes to her fourth toe, she displayed erythema and lymphangitic streaking up her dorsal foot. While she was afebrile, her white cell count was 13,000/mcL. Radiographic examinations did not show signs of osteomyelitis. Noninvasive vascular evaluations revealed an ankle brachial index of 0.4 and a toe pressure of 10 mm Hg. An aortogram with a lower-extremity runoff arteriogram confirmed the obstruction of her left femoral-popliteal bypass.

Taking these results into account, her WIfI score was determined as: wound 2 (moderate), ischemia 3 (severe), foot infection 2 (moderate, no sepsis), translating to a clinical stage 4. This denotes a high risk for major amputation.

Following a team discussion, she was taken to the operating room for an initial debridement of her infection which consisted of a partial fourth ray resection to the level of the mid-metatarsal. Following control of the infection, she received a vascular assessment which ultimately constituted a femoral to distal anterior tibial bypass. Following both of these, she was discharged on a negative-pressure wound therapy device, receiving a split-thickness skin graft 4 weeks later.

The guidelines also emphasize the need for specific training, skills, and experience to ensure the accuracy of the recommended systems for characterizing foot ulcers. The person applying these systems should be appropriately trained and, according to their national or regional standards, should have the knowledge, expertise, and skills necessary to manage people with a diabetes-related foot ulcer.

As we continue to navigate the complexities of diabetes-related foot disease, these guidelines serve as a valuable compass, guiding our decisions and actions. They remind us of the importance of continuous learning, collaboration, and the application of evidence-based practice in our work.

I encourage you to delve into these guidelines. Let’s use them to improve our practice, enhance our communication, and, ultimately, provide better care for our patients.

Dr. Armstrong is professor of surgery, director of limb preservation, University of Southern California, Los Angeles. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

As we navigate the ever-evolving landscape of diabetic foot disease management, I’d like to discuss the updated 2023 International Working Group on the Diabetic Foot guidelines and their implications for our practice. The goal is to create a common language of risk that is easily related from clinician to clinician to patient.

Whatever language we use, though, the problem we face is vast:

• Diabetic foot ulcers affect approximately 18.6 million people worldwide and 1.6 million in the United States each year.
• They are associated with high rates of premature death, with a 5-year mortality rate of 30%. This rate is greater than 70% for those with above-foot amputations, worse than all but the most aggressive cancers.
• The direct costs of treating diabetic foot ulcers in the United States is estimated at $9 billion-$13 billion annually.
• Over 550 million people worldwide have diabetes, with 18.6 million developing foot ulcers annually. Up to 34% of those with diabetes will develop a foot ulcer.
• About 20% of those with a diabetic foot ulcer will undergo amputation, a major cause of which is infection, which affects 50% of foot ulcers.
• Up to 20% of those with a foot ulcer require hospitalization, with 15%-20% undergoing amputation. Inequities exist in diabetes-related foot complications:
• –Rates of major amputation are higher in non-Hispanic Black, Hispanic, and Native American populations, compared with non-Hispanic White populations.
• –Non-Hispanic Black and Hispanic populations present with more advanced ulcers and peripheral artery disease, and are more likely to undergo amputation without revascularization attempt.

The IWGDF, a multidisciplinary team of international experts, has recently updated its guidelines. This team, comprising endocrinologists, internal medicine physicians, physiatrists, podiatrists, and vascular surgeons from across the globe, has worked tirelessly to provide us with a comprehensive guide to managing diabetes-related foot ulcers.

The updated guidelines address five critical clinical questions, each with up to 13 important outcomes. The systematic review that underpins these guidelines identified 149 eligible studies, assessing 28 different systems. This exhaustive research has led to the development of seven key recommendations that address the clinical questions and consider the existence of different clinical settings.

One of the significant updates in the 2023 guidelines is the recommendation of SINBAD – site, ischemia, neuropathy, bacterial infection, area, and depth – as the priority wound classification system for people with diabetes and a foot ulcer. This system is particularly useful for interprofessional communication, describing each composite variable, and conducting clinical audits using the full score. However, the guidelines also recommend the use of other, more specific assessment systems for infection and peripheral artery disease from the Infectious Diseases Society of America/IWGDF when resources and an appropriate level of expertise exist.

The introduction of the Wound, Ischemia and Foot Infection (WIfI) classification system in the guidelines is also a noteworthy development. This system is crucial in assessing perfusion and the likely benefit of revascularization in a person with diabetes and a foot ulcer. By assessing the level of wound ischemia and infection, we can make informed decisions about the need for vascular intervention, which can significantly affect the patient’s outcome. This can be done simply by classifying each of the three categories of wound, ischemia, or foot infection as none, mild, moderate, or severe. By simplifying the very dynamic comorbidities of tissue loss, ischemia, and infection into a usable and predictive scale, it helps us to communicate risk across disciplines. This has been found to be highly predictive of healing, amputation, and mortality.

We use WIfI every day across our system. An example might include a patient we recently treated:

A 76-year-old woman presented with a wound to her left foot. Her past medical history revealed type 2 diabetes, peripheral neuropathy, and documented peripheral artery disease with prior bilateral femoral-popliteal bypass conducted at an external facility. In addition to gangrenous changes to her fourth toe, she displayed erythema and lymphangitic streaking up her dorsal foot. While she was afebrile, her white cell count was 13,000/mcL. Radiographic examinations did not show signs of osteomyelitis. Noninvasive vascular evaluations revealed an ankle brachial index of 0.4 and a toe pressure of 10 mm Hg. An aortogram with a lower-extremity runoff arteriogram confirmed the obstruction of her left femoral-popliteal bypass.

Taking these results into account, her WIfI score was determined as: wound 2 (moderate), ischemia 3 (severe), foot infection 2 (moderate, no sepsis), translating to a clinical stage 4. This denotes a high risk for major amputation.

Following a team discussion, she was taken to the operating room for an initial debridement of her infection which consisted of a partial fourth ray resection to the level of the mid-metatarsal. Following control of the infection, she received a vascular assessment which ultimately constituted a femoral to distal anterior tibial bypass. Following both of these, she was discharged on a negative-pressure wound therapy device, receiving a split-thickness skin graft 4 weeks later.

The guidelines also emphasize the need for specific training, skills, and experience to ensure the accuracy of the recommended systems for characterizing foot ulcers. The person applying these systems should be appropriately trained and, according to their national or regional standards, should have the knowledge, expertise, and skills necessary to manage people with a diabetes-related foot ulcer.

As we continue to navigate the complexities of diabetes-related foot disease, these guidelines serve as a valuable compass, guiding our decisions and actions. They remind us of the importance of continuous learning, collaboration, and the application of evidence-based practice in our work.

I encourage you to delve into these guidelines. Let’s use them to improve our practice, enhance our communication, and, ultimately, provide better care for our patients.

Dr. Armstrong is professor of surgery, director of limb preservation, University of Southern California, Los Angeles. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Deanna Denham Hughes was stunned when she was diagnosed with ovarian cancer in 2022. She was only 32. She had no family history of cancer, and tests found no genetic link. Ms. Hughes wondered why she, an otherwise healthy Black mother of two, would develop a malignancy known as a “silent killer.”

After emergency surgery to remove the mass, along with her ovaries, uterus, fallopian tubes, and appendix, Ms. Hughes said, she saw an Instagram post in which a woman with uterine cancer linked her condition to chemical hair straighteners.

“I almost fell over,” she said from her home in Smyrna, Ga.

When Ms. Hughes was about 4, her mother began applying a chemical straightener, or relaxer, to her hair every 6-8 weeks. “It burned, and it smelled awful,” Ms. Hughes recalled. “But it was just part of our routine to ‘deal with my hair.’ ”

The routine continued until she went to college and met other Black women who wore their hair naturally. Soon, Ms. Hughes quit relaxers.

Social and economic pressures have long compelled Black girls and women to straighten their hair to conform to Eurocentric beauty standards. But chemical straighteners are stinky and costly and sometimes cause painful scalp burns. Mounting evidence now shows they could be a health hazard.

Relaxers can contain carcinogens, such as formaldehyde-releasing agents, phthalates, and other endocrine-disrupting compounds, according to National Institutes of Health studies. The compounds can mimic the body’s hormones and have been linked to breast, uterine, and ovarian cancers, studies show.

African American women’s often frequent and lifelong application of chemical relaxers to their hair and scalp might explain why hormone-related cancers kill disproportionately more Black than White women, say researchers and cancer doctors.

“What’s in these products is harmful,” said Tamarra James-Todd, PhD, an epidemiology professor at Harvard T.H. Chan School of Public Health, Boston, who has studied straightening products for the past 20 years.

She believes manufacturers, policymakers, and physicians should warn consumers that relaxers might cause cancer and other health problems.

But regulators have been slow to act, physicians have been reluctant to take up the cause, and racism continues to dictate fashion standards that make it tough for women to quit relaxers, products so addictive they’re known as “creamy crack.”

Michelle Obama straightened her hair when Barack Obama served as president because she believed Americans were “not ready” to see her in braids, the former first lady said after leaving the White House. The U.S. military still prohibited popular Black hairstyles such as dreadlocks and twists while the nation’s first Black president was in office.

California in 2019 became the first of nearly two dozen states to ban race-based hair discrimination. Last year, the U.S. House of Representatives passed similar legislation, known as the CROWN Act, for Creating a Respectful and Open World for Natural Hair. But the bill failed in the Senate.

The need for legislation underscores the challenges Black girls and women face at school and in the workplace.

“You have to pick your struggles,” said Atlanta-based surgical oncologist Ryland J. Gore, MD. She informs her breast cancer patients about the increased cancer risk from relaxers. Despite her knowledge, however, Dr. Gore continues to use chemical straighteners on her own hair, as she has since she was about 7 years old.

“Your hair tells a story,” she said.

In conversations with patients, Dr. Gore sometimes talks about how African American women once wove messages into their braids about the route to take on the Underground Railroad as they sought freedom from slavery.

“It’s just a deep discussion,” one that touches on culture, history, and research into current hairstyling practices, she said. “The data is out there. So patients should be warned, and then they can make a decision.”

The first hint of a connection between hair products and health issues surfaced in the 1990s. Doctors began seeing signs of sexual maturation in Black babies and young girls who developed breasts and pubic hair after using shampoo containing estrogen or placental extract. When the girls stopped using the shampoo, the hair and breast development receded, according to a study published in the journal Clinical Pediatrics in 1998.

Since then, Dr. James-Todd and other researchers have linked chemicals in hair products to a variety of health issues more prevalent among Black women – from early puberty to preterm birth, obesity, and diabetes.

In recent years, researchers have focused on a possible connection between ingredients in chemical relaxers and hormone-related cancers, like the one Ms. Hughes developed, which tend to be more aggressive and deadly in Black women.

A 2017 study found White women who used chemical relaxers were nearly twice as likely to develop breast cancer as those who did not use them. Because the vast majority of the Black study participants used relaxers, researchers could not effectively test the association in Black women, said lead author Adana Llanos, PhD, associate professor of epidemiology at Columbia University’s Mailman School of Public Health, New York.

Researchers did test it in 2020.

The so-called Sister Study, a landmark National Institute of Environmental Health Sciences investigation into the causes of breast cancer and related diseases, followed 50,000 U.S. women whose sisters had been diagnosed with breast cancer and who were cancer-free when they enrolled. Regardless of race, women who reported using relaxers in the prior year were 18% more likely to be diagnosed with breast cancer. Those who used relaxers at least every 5-8 weeks had a 31% higher breast cancer risk.

Nearly 75% of the Black sisters used relaxers in the prior year, compared with 3% of the non-Hispanic White sisters. Three-quarters of Black women self-reported using the straighteners as adolescents, and frequent use of chemical straighteners during adolescence raised the risk of premenopausal breast cancer, a 2021 NIH-funded study in the International Journal of Cancer found.

Another 2021 analysis of the Sister Study data showed sisters who self-reported that they frequently used relaxers or pressing products doubled their ovarian cancer risk. In 2022, another study found frequent use more than doubled uterine cancer risk.

After researchers discovered the link with uterine cancer, some called for policy changes and other measures to reduce exposure to chemical relaxers.

“It is time to intervene,” Dr. Llanos and her colleagues wrote in a Journal of the National Cancer Institute editorial accompanying the uterine cancer analysis. While acknowledging the need for more research, they issued a “call for action.”

No one can say that using permanent hair straighteners will give you cancer, Dr. Llanos said in an interview. “That’s not how cancer works,” she said, noting that some smokers never develop lung cancer, despite tobacco use being a known risk factor.

The body of research linking hair straighteners and cancer is more limited, said Dr. Llanos, who quit using chemical relaxers 15 years ago. But, she asked rhetorically, “Do we need to do the research for 50 more years to know that chemical relaxers are harmful?”

Charlotte R. Gamble, MD, a gynecological oncologist whose Washington, D.C., practice includes Black women with uterine and ovarian cancer, said she and her colleagues see the uterine cancer study findings as worthy of further exploration – but not yet worthy of discussion with patients.

“The jury’s out for me personally,” she said. “There’s so much more data that’s needed.”

Meanwhile, Dr. James-Todd and other researchers believe they have built a solid body of evidence.

“There are enough things we do know to begin taking action, developing interventions, providing useful information to clinicians and patients and the general public,” said Traci N. Bethea, PhD, assistant professor in the Office of Minority Health and Health Disparities Research at Georgetown University.

Responsibility for regulating personal-care products, including chemical hair straighteners and hair dyes – which also have been linked to hormone-related cancers – lies with the Food and Drug Administration. But the FDA does not subject personal-care products to the same approval process it uses for food and drugs. The FDA restricts only 11 categories of chemicals used in cosmetics, while concerns about health effects have prompted the European Union to restrict the use of at least 2,400 substances.

In March, Reps. Ayanna Pressley (D-Mass.) and Shontel Brown (D-Ohio) asked the FDA to investigate the potential health threat posed by chemical relaxers. An FDA representative said the agency would look into it.

Natural hairstyles are enjoying a resurgence among Black girls and women, but many continue to rely on the creamy crack, said Dede Teteh, DrPH, assistant professor of public health at Chapman University, Irvine, Calif.

She had her first straightening perm at 8 and has struggled to withdraw from relaxers as an adult, said Dr. Teteh, who now wears locs. Not long ago, she considered chemically straightening her hair for an academic job interview because she didn’t want her hair to “be a hindrance” when she appeared before White professors.

Dr. Teteh led “The Cost of Beauty,” a hair-health research project published in 2017. She and her team interviewed 91 Black women in Southern California. Some became “combative” at the idea of quitting relaxers and claimed “everything can cause cancer.”

Their reactions speak to the challenges Black women face in America, Dr. Teteh said.

“It’s not that people do not want to hear the information related to their health,” she said. “But they want people to share the information in a way that it’s really empathetic to the plight of being Black here in the United States.”
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

Deanna Denham Hughes was stunned when she was diagnosed with ovarian cancer in 2022. She was only 32. She had no family history of cancer, and tests found no genetic link. Ms. Hughes wondered why she, an otherwise healthy Black mother of two, would develop a malignancy known as a “silent killer.”

After emergency surgery to remove the mass, along with her ovaries, uterus, fallopian tubes, and appendix, Ms. Hughes said, she saw an Instagram post in which a woman with uterine cancer linked her condition to chemical hair straighteners.

“I almost fell over,” she said from her home in Smyrna, Ga.

When Ms. Hughes was about 4, her mother began applying a chemical straightener, or relaxer, to her hair every 6-8 weeks. “It burned, and it smelled awful,” Ms. Hughes recalled. “But it was just part of our routine to ‘deal with my hair.’ ”

The routine continued until she went to college and met other Black women who wore their hair naturally. Soon, Ms. Hughes quit relaxers.

Social and economic pressures have long compelled Black girls and women to straighten their hair to conform to Eurocentric beauty standards. But chemical straighteners are stinky and costly and sometimes cause painful scalp burns. Mounting evidence now shows they could be a health hazard.

Relaxers can contain carcinogens, such as formaldehyde-releasing agents, phthalates, and other endocrine-disrupting compounds, according to National Institutes of Health studies. The compounds can mimic the body’s hormones and have been linked to breast, uterine, and ovarian cancers, studies show.

African American women’s often frequent and lifelong application of chemical relaxers to their hair and scalp might explain why hormone-related cancers kill disproportionately more Black than White women, say researchers and cancer doctors.

“What’s in these products is harmful,” said Tamarra James-Todd, PhD, an epidemiology professor at Harvard T.H. Chan School of Public Health, Boston, who has studied straightening products for the past 20 years.

She believes manufacturers, policymakers, and physicians should warn consumers that relaxers might cause cancer and other health problems.

But regulators have been slow to act, physicians have been reluctant to take up the cause, and racism continues to dictate fashion standards that make it tough for women to quit relaxers, products so addictive they’re known as “creamy crack.”

Michelle Obama straightened her hair when Barack Obama served as president because she believed Americans were “not ready” to see her in braids, the former first lady said after leaving the White House. The U.S. military still prohibited popular Black hairstyles such as dreadlocks and twists while the nation’s first Black president was in office.

California in 2019 became the first of nearly two dozen states to ban race-based hair discrimination. Last year, the U.S. House of Representatives passed similar legislation, known as the CROWN Act, for Creating a Respectful and Open World for Natural Hair. But the bill failed in the Senate.

The need for legislation underscores the challenges Black girls and women face at school and in the workplace.

“You have to pick your struggles,” said Atlanta-based surgical oncologist Ryland J. Gore, MD. She informs her breast cancer patients about the increased cancer risk from relaxers. Despite her knowledge, however, Dr. Gore continues to use chemical straighteners on her own hair, as she has since she was about 7 years old.

“Your hair tells a story,” she said.

In conversations with patients, Dr. Gore sometimes talks about how African American women once wove messages into their braids about the route to take on the Underground Railroad as they sought freedom from slavery.

“It’s just a deep discussion,” one that touches on culture, history, and research into current hairstyling practices, she said. “The data is out there. So patients should be warned, and then they can make a decision.”

The first hint of a connection between hair products and health issues surfaced in the 1990s. Doctors began seeing signs of sexual maturation in Black babies and young girls who developed breasts and pubic hair after using shampoo containing estrogen or placental extract. When the girls stopped using the shampoo, the hair and breast development receded, according to a study published in the journal Clinical Pediatrics in 1998.

Since then, Dr. James-Todd and other researchers have linked chemicals in hair products to a variety of health issues more prevalent among Black women – from early puberty to preterm birth, obesity, and diabetes.

In recent years, researchers have focused on a possible connection between ingredients in chemical relaxers and hormone-related cancers, like the one Ms. Hughes developed, which tend to be more aggressive and deadly in Black women.

A 2017 study found White women who used chemical relaxers were nearly twice as likely to develop breast cancer as those who did not use them. Because the vast majority of the Black study participants used relaxers, researchers could not effectively test the association in Black women, said lead author Adana Llanos, PhD, associate professor of epidemiology at Columbia University’s Mailman School of Public Health, New York.

Researchers did test it in 2020.

The so-called Sister Study, a landmark National Institute of Environmental Health Sciences investigation into the causes of breast cancer and related diseases, followed 50,000 U.S. women whose sisters had been diagnosed with breast cancer and who were cancer-free when they enrolled. Regardless of race, women who reported using relaxers in the prior year were 18% more likely to be diagnosed with breast cancer. Those who used relaxers at least every 5-8 weeks had a 31% higher breast cancer risk.

Nearly 75% of the Black sisters used relaxers in the prior year, compared with 3% of the non-Hispanic White sisters. Three-quarters of Black women self-reported using the straighteners as adolescents, and frequent use of chemical straighteners during adolescence raised the risk of premenopausal breast cancer, a 2021 NIH-funded study in the International Journal of Cancer found.

Another 2021 analysis of the Sister Study data showed sisters who self-reported that they frequently used relaxers or pressing products doubled their ovarian cancer risk. In 2022, another study found frequent use more than doubled uterine cancer risk.

After researchers discovered the link with uterine cancer, some called for policy changes and other measures to reduce exposure to chemical relaxers.

“It is time to intervene,” Dr. Llanos and her colleagues wrote in a Journal of the National Cancer Institute editorial accompanying the uterine cancer analysis. While acknowledging the need for more research, they issued a “call for action.”

No one can say that using permanent hair straighteners will give you cancer, Dr. Llanos said in an interview. “That’s not how cancer works,” she said, noting that some smokers never develop lung cancer, despite tobacco use being a known risk factor.

The body of research linking hair straighteners and cancer is more limited, said Dr. Llanos, who quit using chemical relaxers 15 years ago. But, she asked rhetorically, “Do we need to do the research for 50 more years to know that chemical relaxers are harmful?”

Charlotte R. Gamble, MD, a gynecological oncologist whose Washington, D.C., practice includes Black women with uterine and ovarian cancer, said she and her colleagues see the uterine cancer study findings as worthy of further exploration – but not yet worthy of discussion with patients.

“The jury’s out for me personally,” she said. “There’s so much more data that’s needed.”

Meanwhile, Dr. James-Todd and other researchers believe they have built a solid body of evidence.

“There are enough things we do know to begin taking action, developing interventions, providing useful information to clinicians and patients and the general public,” said Traci N. Bethea, PhD, assistant professor in the Office of Minority Health and Health Disparities Research at Georgetown University.

Responsibility for regulating personal-care products, including chemical hair straighteners and hair dyes – which also have been linked to hormone-related cancers – lies with the Food and Drug Administration. But the FDA does not subject personal-care products to the same approval process it uses for food and drugs. The FDA restricts only 11 categories of chemicals used in cosmetics, while concerns about health effects have prompted the European Union to restrict the use of at least 2,400 substances.

In March, Reps. Ayanna Pressley (D-Mass.) and Shontel Brown (D-Ohio) asked the FDA to investigate the potential health threat posed by chemical relaxers. An FDA representative said the agency would look into it.

Natural hairstyles are enjoying a resurgence among Black girls and women, but many continue to rely on the creamy crack, said Dede Teteh, DrPH, assistant professor of public health at Chapman University, Irvine, Calif.

She had her first straightening perm at 8 and has struggled to withdraw from relaxers as an adult, said Dr. Teteh, who now wears locs. Not long ago, she considered chemically straightening her hair for an academic job interview because she didn’t want her hair to “be a hindrance” when she appeared before White professors.

Dr. Teteh led “The Cost of Beauty,” a hair-health research project published in 2017. She and her team interviewed 91 Black women in Southern California. Some became “combative” at the idea of quitting relaxers and claimed “everything can cause cancer.”

Their reactions speak to the challenges Black women face in America, Dr. Teteh said.

“It’s not that people do not want to hear the information related to their health,” she said. “But they want people to share the information in a way that it’s really empathetic to the plight of being Black here in the United States.”
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

Deanna Denham Hughes was stunned when she was diagnosed with ovarian cancer in 2022. She was only 32. She had no family history of cancer, and tests found no genetic link. Ms. Hughes wondered why she, an otherwise healthy Black mother of two, would develop a malignancy known as a “silent killer.”

After emergency surgery to remove the mass, along with her ovaries, uterus, fallopian tubes, and appendix, Ms. Hughes said, she saw an Instagram post in which a woman with uterine cancer linked her condition to chemical hair straighteners.

“I almost fell over,” she said from her home in Smyrna, Ga.

When Ms. Hughes was about 4, her mother began applying a chemical straightener, or relaxer, to her hair every 6-8 weeks. “It burned, and it smelled awful,” Ms. Hughes recalled. “But it was just part of our routine to ‘deal with my hair.’ ”

The routine continued until she went to college and met other Black women who wore their hair naturally. Soon, Ms. Hughes quit relaxers.

Social and economic pressures have long compelled Black girls and women to straighten their hair to conform to Eurocentric beauty standards. But chemical straighteners are stinky and costly and sometimes cause painful scalp burns. Mounting evidence now shows they could be a health hazard.

Relaxers can contain carcinogens, such as formaldehyde-releasing agents, phthalates, and other endocrine-disrupting compounds, according to National Institutes of Health studies. The compounds can mimic the body’s hormones and have been linked to breast, uterine, and ovarian cancers, studies show.

African American women’s often frequent and lifelong application of chemical relaxers to their hair and scalp might explain why hormone-related cancers kill disproportionately more Black than White women, say researchers and cancer doctors.

“What’s in these products is harmful,” said Tamarra James-Todd, PhD, an epidemiology professor at Harvard T.H. Chan School of Public Health, Boston, who has studied straightening products for the past 20 years.

She believes manufacturers, policymakers, and physicians should warn consumers that relaxers might cause cancer and other health problems.

But regulators have been slow to act, physicians have been reluctant to take up the cause, and racism continues to dictate fashion standards that make it tough for women to quit relaxers, products so addictive they’re known as “creamy crack.”

Michelle Obama straightened her hair when Barack Obama served as president because she believed Americans were “not ready” to see her in braids, the former first lady said after leaving the White House. The U.S. military still prohibited popular Black hairstyles such as dreadlocks and twists while the nation’s first Black president was in office.

California in 2019 became the first of nearly two dozen states to ban race-based hair discrimination. Last year, the U.S. House of Representatives passed similar legislation, known as the CROWN Act, for Creating a Respectful and Open World for Natural Hair. But the bill failed in the Senate.

The need for legislation underscores the challenges Black girls and women face at school and in the workplace.

“You have to pick your struggles,” said Atlanta-based surgical oncologist Ryland J. Gore, MD. She informs her breast cancer patients about the increased cancer risk from relaxers. Despite her knowledge, however, Dr. Gore continues to use chemical straighteners on her own hair, as she has since she was about 7 years old.

“Your hair tells a story,” she said.

In conversations with patients, Dr. Gore sometimes talks about how African American women once wove messages into their braids about the route to take on the Underground Railroad as they sought freedom from slavery.

“It’s just a deep discussion,” one that touches on culture, history, and research into current hairstyling practices, she said. “The data is out there. So patients should be warned, and then they can make a decision.”

The first hint of a connection between hair products and health issues surfaced in the 1990s. Doctors began seeing signs of sexual maturation in Black babies and young girls who developed breasts and pubic hair after using shampoo containing estrogen or placental extract. When the girls stopped using the shampoo, the hair and breast development receded, according to a study published in the journal Clinical Pediatrics in 1998.

Since then, Dr. James-Todd and other researchers have linked chemicals in hair products to a variety of health issues more prevalent among Black women – from early puberty to preterm birth, obesity, and diabetes.

In recent years, researchers have focused on a possible connection between ingredients in chemical relaxers and hormone-related cancers, like the one Ms. Hughes developed, which tend to be more aggressive and deadly in Black women.

A 2017 study found White women who used chemical relaxers were nearly twice as likely to develop breast cancer as those who did not use them. Because the vast majority of the Black study participants used relaxers, researchers could not effectively test the association in Black women, said lead author Adana Llanos, PhD, associate professor of epidemiology at Columbia University’s Mailman School of Public Health, New York.

Researchers did test it in 2020.

The so-called Sister Study, a landmark National Institute of Environmental Health Sciences investigation into the causes of breast cancer and related diseases, followed 50,000 U.S. women whose sisters had been diagnosed with breast cancer and who were cancer-free when they enrolled. Regardless of race, women who reported using relaxers in the prior year were 18% more likely to be diagnosed with breast cancer. Those who used relaxers at least every 5-8 weeks had a 31% higher breast cancer risk.

Nearly 75% of the Black sisters used relaxers in the prior year, compared with 3% of the non-Hispanic White sisters. Three-quarters of Black women self-reported using the straighteners as adolescents, and frequent use of chemical straighteners during adolescence raised the risk of premenopausal breast cancer, a 2021 NIH-funded study in the International Journal of Cancer found.

Another 2021 analysis of the Sister Study data showed sisters who self-reported that they frequently used relaxers or pressing products doubled their ovarian cancer risk. In 2022, another study found frequent use more than doubled uterine cancer risk.

After researchers discovered the link with uterine cancer, some called for policy changes and other measures to reduce exposure to chemical relaxers.

“It is time to intervene,” Dr. Llanos and her colleagues wrote in a Journal of the National Cancer Institute editorial accompanying the uterine cancer analysis. While acknowledging the need for more research, they issued a “call for action.”

No one can say that using permanent hair straighteners will give you cancer, Dr. Llanos said in an interview. “That’s not how cancer works,” she said, noting that some smokers never develop lung cancer, despite tobacco use being a known risk factor.

The body of research linking hair straighteners and cancer is more limited, said Dr. Llanos, who quit using chemical relaxers 15 years ago. But, she asked rhetorically, “Do we need to do the research for 50 more years to know that chemical relaxers are harmful?”

Charlotte R. Gamble, MD, a gynecological oncologist whose Washington, D.C., practice includes Black women with uterine and ovarian cancer, said she and her colleagues see the uterine cancer study findings as worthy of further exploration – but not yet worthy of discussion with patients.

“The jury’s out for me personally,” she said. “There’s so much more data that’s needed.”

Meanwhile, Dr. James-Todd and other researchers believe they have built a solid body of evidence.

“There are enough things we do know to begin taking action, developing interventions, providing useful information to clinicians and patients and the general public,” said Traci N. Bethea, PhD, assistant professor in the Office of Minority Health and Health Disparities Research at Georgetown University.

Responsibility for regulating personal-care products, including chemical hair straighteners and hair dyes – which also have been linked to hormone-related cancers – lies with the Food and Drug Administration. But the FDA does not subject personal-care products to the same approval process it uses for food and drugs. The FDA restricts only 11 categories of chemicals used in cosmetics, while concerns about health effects have prompted the European Union to restrict the use of at least 2,400 substances.

In March, Reps. Ayanna Pressley (D-Mass.) and Shontel Brown (D-Ohio) asked the FDA to investigate the potential health threat posed by chemical relaxers. An FDA representative said the agency would look into it.

Natural hairstyles are enjoying a resurgence among Black girls and women, but many continue to rely on the creamy crack, said Dede Teteh, DrPH, assistant professor of public health at Chapman University, Irvine, Calif.

She had her first straightening perm at 8 and has struggled to withdraw from relaxers as an adult, said Dr. Teteh, who now wears locs. Not long ago, she considered chemically straightening her hair for an academic job interview because she didn’t want her hair to “be a hindrance” when she appeared before White professors.

Dr. Teteh led “The Cost of Beauty,” a hair-health research project published in 2017. She and her team interviewed 91 Black women in Southern California. Some became “combative” at the idea of quitting relaxers and claimed “everything can cause cancer.”

Their reactions speak to the challenges Black women face in America, Dr. Teteh said.

“It’s not that people do not want to hear the information related to their health,” she said. “But they want people to share the information in a way that it’s really empathetic to the plight of being Black here in the United States.”
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.

Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that use of injectable agonists of glucagonlike peptide-1 (GLP1) appears to hasten the progression of diabetic retinopathy and diabetic macular edema (DME).

Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.

Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.

GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.

Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
 

Albiglutide the key culprit?

In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).

Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.

“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
 

What causes progression?

Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.

“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”

The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.

Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that use of injectable agonists of glucagonlike peptide-1 (GLP1) appears to hasten the progression of diabetic retinopathy and diabetic macular edema (DME).

Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.

Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.

GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.

Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
 

Albiglutide the key culprit?

In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).

Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.

“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
 

What causes progression?

Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.

“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”

The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.

Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that use of injectable agonists of glucagonlike peptide-1 (GLP1) appears to hasten the progression of diabetic retinopathy and diabetic macular edema (DME).

Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.

Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.

GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.

Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
 

Albiglutide the key culprit?

In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).

Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.

“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
 

What causes progression?

Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.

“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”

The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

Time-restricted eating (TRE) can be a practical, easy-to-follow way for some people to control their daily food intake and lose weight. It precludes a person’s need to pay close attention to how much they eat as long as they confine consumption to a limited time window. Plus, results from several recent studies show TRE can further benefit people with type 2 diabetes as well as obesity via mechanisms beyond weight loss.

The most tested and recommended eating window is 8 hours long, although periods up to roughly 10 hours may provide some benefits. Results from multiple studies document that TRE produces modest but consistent weight loss of less than 5% in many people. A recent meta-analysis of 17 randomized controlled studies involving 899 people showed an overall incremental weight loss, compared with controls of 1.60 kg on a TRE regimen.

The more limited data collected so far in people with type 2 diabetes show additional metabolic benefits from TRE, including improved beta-cell responsiveness, increased insulin sensitivity, nonoxidative glucose disposal, increased time in glycemic range, and virtually no hypoglycemic events, Courtney Peterson, PhD, said at the annual scientific sessions of the American Diabetes Association.

‘Eating earlier is better’

An advantage of TRE is that it is “agnostic to food preferences and quality,” said Lisa S. Chow, MD, during a separate session at the meeting. TRE “may have benefits beyond calorie restriction” that appear related to “the timing of eating and the extent of the eating window restriction. Eating earlier [in the day] is better” for markers of metabolic health regardless of how much weight a person may lose on a TRE regimen, noted Dr. Chow, an endocrinologist and professor at the University of Minnesota Medical School, Minneapolis.

But the TRE paradigm seems amenable to some flexibility on the timing for the eating window while still having benefit.

“Self-selected eating windows are usually late,” Dr. Chow observed, and because compliance with a constrained eating window matters, it may be worth allowing people to choose whichever time window for eating works best for them.

“If you let people pick their eating window, they typically include dinner,” said Dr. Chow, who has run a small TRE study that showed this.

“To maximize the effects [of TRE] people should use the eating window that best fits their life,” agreed Kelsey Gabel, PhD, who also gave a TRE talk during the meeting. “Eating most of your [daily] calories first thing in the morning would have the best cardiometabolic benefit, but reduced adherence would mitigate the benefit,” said Dr. Gabel, a nutrition researcher at the University of Illinois.
 

‘Meeting people where they’re at’

“We can have a larger public health impact by meeting people where they’re at. People should position their eating window where it best fits so they can achieve calorie restriction without even knowing it,” Dr. Gabel advised.

She cited a report as evidence that most people prefer a later eating window. The report reviewed observational data from nearly 800,000 people who used either of two different TRE phone apps. The data showed that most people opted to start their daily eating during 11:00 AM-1:00 PM, and then stop during 6:00 PM-8:00 PM.

“TRE will not solve all of our obesity problems, but it’s a good place to start,” Dr. Gabel declared.

For people who include dinner at a typical evening time in their TRE window, a key message is that “dinner is your last food of the day. There’s no snacking later,” said Dr. Chow.

“The biggest challenge is adherence,” said Dr. Peterson. “Fewer people want to do TRE than you think. We know that calorie restriction works. We just need a way for people to do it,” and for at least some people, TRE is that way. While no evidence clearly shows that 8 hours is the best eating-window duration, “we think 8 hours is a good sweet-spot for motivated people,” she said.
 

Sparser data on TRE in people with T2D

Fewer studies have examined the impact of TRE on glycemic control, insulin sensitivity, and related effects in people with type 2 diabetes. According to Dr. Peterson, published reports currently include two randomized controlled studies and three single-arm studies in people with type 2 diabetes and an additional two studies in people with prediabetes.

The largest of these reports randomized 120 adults in China with type 2 diabetes and overweight to TRE using a 10-hour eating window (8:00 AM-6:00 PM) or unrestricted eating for 12 weeks. By the end of the study, those on the TRE regimen had an average reduction in their hemoglobin A1c from baseline that was 0.88 percentage points greater than among the controls, and the TRE arm had also lost an average of nearly 2.15 kg more from baseline than the controls.

Dr. Peterson highlighted the importance of expanding research using TRE in people with type 2 diabetes.

Dr. Peterson and Dr. Gabel report no relevant financial relationships. Dr. Chow has received research support from Dexcom.

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

Time-restricted eating (TRE) can be a practical, easy-to-follow way for some people to control their daily food intake and lose weight. It precludes a person’s need to pay close attention to how much they eat as long as they confine consumption to a limited time window. Plus, results from several recent studies show TRE can further benefit people with type 2 diabetes as well as obesity via mechanisms beyond weight loss.

The most tested and recommended eating window is 8 hours long, although periods up to roughly 10 hours may provide some benefits. Results from multiple studies document that TRE produces modest but consistent weight loss of less than 5% in many people. A recent meta-analysis of 17 randomized controlled studies involving 899 people showed an overall incremental weight loss, compared with controls of 1.60 kg on a TRE regimen.

The more limited data collected so far in people with type 2 diabetes show additional metabolic benefits from TRE, including improved beta-cell responsiveness, increased insulin sensitivity, nonoxidative glucose disposal, increased time in glycemic range, and virtually no hypoglycemic events, Courtney Peterson, PhD, said at the annual scientific sessions of the American Diabetes Association.

‘Eating earlier is better’

An advantage of TRE is that it is “agnostic to food preferences and quality,” said Lisa S. Chow, MD, during a separate session at the meeting. TRE “may have benefits beyond calorie restriction” that appear related to “the timing of eating and the extent of the eating window restriction. Eating earlier [in the day] is better” for markers of metabolic health regardless of how much weight a person may lose on a TRE regimen, noted Dr. Chow, an endocrinologist and professor at the University of Minnesota Medical School, Minneapolis.

But the TRE paradigm seems amenable to some flexibility on the timing for the eating window while still having benefit.

“Self-selected eating windows are usually late,” Dr. Chow observed, and because compliance with a constrained eating window matters, it may be worth allowing people to choose whichever time window for eating works best for them.

“If you let people pick their eating window, they typically include dinner,” said Dr. Chow, who has run a small TRE study that showed this.

“To maximize the effects [of TRE] people should use the eating window that best fits their life,” agreed Kelsey Gabel, PhD, who also gave a TRE talk during the meeting. “Eating most of your [daily] calories first thing in the morning would have the best cardiometabolic benefit, but reduced adherence would mitigate the benefit,” said Dr. Gabel, a nutrition researcher at the University of Illinois.
 

‘Meeting people where they’re at’

“We can have a larger public health impact by meeting people where they’re at. People should position their eating window where it best fits so they can achieve calorie restriction without even knowing it,” Dr. Gabel advised.

She cited a report as evidence that most people prefer a later eating window. The report reviewed observational data from nearly 800,000 people who used either of two different TRE phone apps. The data showed that most people opted to start their daily eating during 11:00 AM-1:00 PM, and then stop during 6:00 PM-8:00 PM.

“TRE will not solve all of our obesity problems, but it’s a good place to start,” Dr. Gabel declared.

For people who include dinner at a typical evening time in their TRE window, a key message is that “dinner is your last food of the day. There’s no snacking later,” said Dr. Chow.

“The biggest challenge is adherence,” said Dr. Peterson. “Fewer people want to do TRE than you think. We know that calorie restriction works. We just need a way for people to do it,” and for at least some people, TRE is that way. While no evidence clearly shows that 8 hours is the best eating-window duration, “we think 8 hours is a good sweet-spot for motivated people,” she said.
 

Sparser data on TRE in people with T2D

Fewer studies have examined the impact of TRE on glycemic control, insulin sensitivity, and related effects in people with type 2 diabetes. According to Dr. Peterson, published reports currently include two randomized controlled studies and three single-arm studies in people with type 2 diabetes and an additional two studies in people with prediabetes.

The largest of these reports randomized 120 adults in China with type 2 diabetes and overweight to TRE using a 10-hour eating window (8:00 AM-6:00 PM) or unrestricted eating for 12 weeks. By the end of the study, those on the TRE regimen had an average reduction in their hemoglobin A1c from baseline that was 0.88 percentage points greater than among the controls, and the TRE arm had also lost an average of nearly 2.15 kg more from baseline than the controls.

Dr. Peterson highlighted the importance of expanding research using TRE in people with type 2 diabetes.

Dr. Peterson and Dr. Gabel report no relevant financial relationships. Dr. Chow has received research support from Dexcom.

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

Time-restricted eating (TRE) can be a practical, easy-to-follow way for some people to control their daily food intake and lose weight. It precludes a person’s need to pay close attention to how much they eat as long as they confine consumption to a limited time window. Plus, results from several recent studies show TRE can further benefit people with type 2 diabetes as well as obesity via mechanisms beyond weight loss.

The most tested and recommended eating window is 8 hours long, although periods up to roughly 10 hours may provide some benefits. Results from multiple studies document that TRE produces modest but consistent weight loss of less than 5% in many people. A recent meta-analysis of 17 randomized controlled studies involving 899 people showed an overall incremental weight loss, compared with controls of 1.60 kg on a TRE regimen.

The more limited data collected so far in people with type 2 diabetes show additional metabolic benefits from TRE, including improved beta-cell responsiveness, increased insulin sensitivity, nonoxidative glucose disposal, increased time in glycemic range, and virtually no hypoglycemic events, Courtney Peterson, PhD, said at the annual scientific sessions of the American Diabetes Association.

‘Eating earlier is better’

An advantage of TRE is that it is “agnostic to food preferences and quality,” said Lisa S. Chow, MD, during a separate session at the meeting. TRE “may have benefits beyond calorie restriction” that appear related to “the timing of eating and the extent of the eating window restriction. Eating earlier [in the day] is better” for markers of metabolic health regardless of how much weight a person may lose on a TRE regimen, noted Dr. Chow, an endocrinologist and professor at the University of Minnesota Medical School, Minneapolis.

But the TRE paradigm seems amenable to some flexibility on the timing for the eating window while still having benefit.

“Self-selected eating windows are usually late,” Dr. Chow observed, and because compliance with a constrained eating window matters, it may be worth allowing people to choose whichever time window for eating works best for them.

“If you let people pick their eating window, they typically include dinner,” said Dr. Chow, who has run a small TRE study that showed this.

“To maximize the effects [of TRE] people should use the eating window that best fits their life,” agreed Kelsey Gabel, PhD, who also gave a TRE talk during the meeting. “Eating most of your [daily] calories first thing in the morning would have the best cardiometabolic benefit, but reduced adherence would mitigate the benefit,” said Dr. Gabel, a nutrition researcher at the University of Illinois.
 

‘Meeting people where they’re at’

“We can have a larger public health impact by meeting people where they’re at. People should position their eating window where it best fits so they can achieve calorie restriction without even knowing it,” Dr. Gabel advised.

She cited a report as evidence that most people prefer a later eating window. The report reviewed observational data from nearly 800,000 people who used either of two different TRE phone apps. The data showed that most people opted to start their daily eating during 11:00 AM-1:00 PM, and then stop during 6:00 PM-8:00 PM.

“TRE will not solve all of our obesity problems, but it’s a good place to start,” Dr. Gabel declared.

For people who include dinner at a typical evening time in their TRE window, a key message is that “dinner is your last food of the day. There’s no snacking later,” said Dr. Chow.

“The biggest challenge is adherence,” said Dr. Peterson. “Fewer people want to do TRE than you think. We know that calorie restriction works. We just need a way for people to do it,” and for at least some people, TRE is that way. While no evidence clearly shows that 8 hours is the best eating-window duration, “we think 8 hours is a good sweet-spot for motivated people,” she said.
 

Sparser data on TRE in people with T2D

Fewer studies have examined the impact of TRE on glycemic control, insulin sensitivity, and related effects in people with type 2 diabetes. According to Dr. Peterson, published reports currently include two randomized controlled studies and three single-arm studies in people with type 2 diabetes and an additional two studies in people with prediabetes.

The largest of these reports randomized 120 adults in China with type 2 diabetes and overweight to TRE using a 10-hour eating window (8:00 AM-6:00 PM) or unrestricted eating for 12 weeks. By the end of the study, those on the TRE regimen had an average reduction in their hemoglobin A1c from baseline that was 0.88 percentage points greater than among the controls, and the TRE arm had also lost an average of nearly 2.15 kg more from baseline than the controls.

Dr. Peterson highlighted the importance of expanding research using TRE in people with type 2 diabetes.

Dr. Peterson and Dr. Gabel report no relevant financial relationships. Dr. Chow has received research support from Dexcom.

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

A new lawsuit from a woman with type 2 diabetes alleges that the makers of the drugs Ozempic and Mounjaro did not provide adequate warnings for the severity of stomach problems caused by the popular medicines.

The two drugs, which are Food and Drug Administration approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drug maker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.

In the lawsuit, Jaclyn Bjorklund, 44, of Louisiana, asserts that she was “severely injured” after using Ozempic and Mounjaro and that the pharmaceutical companies failed to disclose the drugs’ risk of causing vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.

The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying” and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain. The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it. 

Ms. Bjorklund has not been diagnosed with gastroparesis, but her symptoms are “indicative of” the condition, her lawyer, Paul Pennock, told NBC News.

Ms. Bjorklund used Ozempic for more than 1 year, and in July 2023 switched to Mounjaro, the lawsuit states. The document, posted on her law firm’s website, details that using the drugs resulted in “severe vomiting, stomach pain, gastrointestinal burning, being hospitalized for stomach issues on several occasions including visits to the emergency room, [and] teeth falling out due to excessive vomiting, requiring additional medications to alleviate her excessive vomiting, and throwing up whole food hours after eating.”

Novo Nordisk spokesperson Natalia Salomao told NBC News that patient safety is “of utmost importance to Novo Nordisk,” and she also noted that gastroparesis is a known risk for people with diabetes. The Food and Drug Administration declined to comment on the case, and Eli Lilly did not immediately respond to a request for comment, NBC News reported.
 

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

A new lawsuit from a woman with type 2 diabetes alleges that the makers of the drugs Ozempic and Mounjaro did not provide adequate warnings for the severity of stomach problems caused by the popular medicines.

The two drugs, which are Food and Drug Administration approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drug maker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.

In the lawsuit, Jaclyn Bjorklund, 44, of Louisiana, asserts that she was “severely injured” after using Ozempic and Mounjaro and that the pharmaceutical companies failed to disclose the drugs’ risk of causing vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.

The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying” and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain. The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it. 

Ms. Bjorklund has not been diagnosed with gastroparesis, but her symptoms are “indicative of” the condition, her lawyer, Paul Pennock, told NBC News.

Ms. Bjorklund used Ozempic for more than 1 year, and in July 2023 switched to Mounjaro, the lawsuit states. The document, posted on her law firm’s website, details that using the drugs resulted in “severe vomiting, stomach pain, gastrointestinal burning, being hospitalized for stomach issues on several occasions including visits to the emergency room, [and] teeth falling out due to excessive vomiting, requiring additional medications to alleviate her excessive vomiting, and throwing up whole food hours after eating.”

Novo Nordisk spokesperson Natalia Salomao told NBC News that patient safety is “of utmost importance to Novo Nordisk,” and she also noted that gastroparesis is a known risk for people with diabetes. The Food and Drug Administration declined to comment on the case, and Eli Lilly did not immediately respond to a request for comment, NBC News reported.
 

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

A new lawsuit from a woman with type 2 diabetes alleges that the makers of the drugs Ozempic and Mounjaro did not provide adequate warnings for the severity of stomach problems caused by the popular medicines.

The two drugs, which are Food and Drug Administration approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drug maker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.

In the lawsuit, Jaclyn Bjorklund, 44, of Louisiana, asserts that she was “severely injured” after using Ozempic and Mounjaro and that the pharmaceutical companies failed to disclose the drugs’ risk of causing vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.

The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying” and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain. The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it. 

Ms. Bjorklund has not been diagnosed with gastroparesis, but her symptoms are “indicative of” the condition, her lawyer, Paul Pennock, told NBC News.

Ms. Bjorklund used Ozempic for more than 1 year, and in July 2023 switched to Mounjaro, the lawsuit states. The document, posted on her law firm’s website, details that using the drugs resulted in “severe vomiting, stomach pain, gastrointestinal burning, being hospitalized for stomach issues on several occasions including visits to the emergency room, [and] teeth falling out due to excessive vomiting, requiring additional medications to alleviate her excessive vomiting, and throwing up whole food hours after eating.”

Novo Nordisk spokesperson Natalia Salomao told NBC News that patient safety is “of utmost importance to Novo Nordisk,” and she also noted that gastroparesis is a known risk for people with diabetes. The Food and Drug Administration declined to comment on the case, and Eli Lilly did not immediately respond to a request for comment, NBC News reported.
 

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

Consuming a higher percentage of calories from added sugars is linked with a higher prevalence of kidney stones, new research suggests.

Though added sugars have been linked with multiple poor health outcomes, their link with kidney stones has been unclear.

Added sugars are sugars or caloric sweeteners added to foods or drinks during processing or preparation to add flavor or shelf life. They do not include natural sugars such as lactose in milk and fructose in fruits.

Researchers, led by Shan Yin, a urologist at Affiliated Hospital of North Sichuan Medical College, in Nanchong, China, compared the added-sugar intake by quartiles in the U.S. National Health and Nutrition Examination Survey 2007-2018.

A total of 28,303 adults were included in this study, with an average age of 48. Women who consumed less than 600 or more than 3,500 kcal or men who consumed less than 800 or more than 4,200 kcal were excluded.

Researchers adjusted for factors including age, race, education, income, physical activity, and marital, employment, and smoking status.

Compared with the first quartile of percentage added-sugar calorie intake, the population in the fourth quartile, with the highest added sugar intake, had a higher prevalence of kidney stones (odds ratio, 1.39; 95% confidence interval, 1.17-1.65).

Compared with the group with fewer than 5% of calories from added sugar, the group that consumed at least 25% of calories from added sugar had nearly twice the prevalence of kidney stones (OR, 1.88; 95% CI, 1.52-2.32).

Findings were published online in Frontiers in Nutrition.

“By identifying this association, policymakers and health professionals can emphasize the need for public health initiatives to reduce added sugar consumption and promote healthy dietary habits,” the authors write.
 

Added sugar in the U.S. diet

Sugar-sweetened beverages such as soft drinks and energy and sports drinks account for 34.4% of added sugars in the American diet. Previous studies have shown the relationship between consuming sugar-sweetened beverages and a higher risk of obesity, diabetes, and cardiovascular disease, diseases that often co-occur with kidney stones.

Researchers note that even though most added sugars in the United States come from sugar-sweetened beverages, it’s unclear whether the association between added sugars and kidney stones is caused by the beverages or other sources. For instance, fructose intake has been found to be independently associated with kidney stones.

How much is too much?

The recommended upper limit on added sugar is controversial and varies widely by health organization. The American Heart Association says daily average intake from added sugars should be no more than 150 kcal for adult males (about 9 teaspoons) and no more than 100 kcal for women (about 6 teaspoons). The Institute of Medicine allows up to 25% of calories to be consumed from added sugars. The 2020 Dietary Guidelines for Americans and World Health Organization set 10% of calories as the recommended upper limit.

Further investigating what causes kidney stones is critical as kidney stones are common worldwide, affecting about 1 in 10 people in the United States alone, and occurrence is increasing. Kidney stones have a high recurrence rate – about half of people who get them have a second episode within 10 years, the authors note.

The researchers acknowledge that because participants self-reported food intake, there is the potential for recall bias. Additionally, because of the cross-sectional design, the researchers were not able to determine whether sugar intake or kidney stone occurrence came first.

This work was supported by the Doctoral Fund Project of North Sichuan Medical College. The authors declare no relevant financial relationships.

Consuming a higher percentage of calories from added sugars is linked with a higher prevalence of kidney stones, new research suggests.

Though added sugars have been linked with multiple poor health outcomes, their link with kidney stones has been unclear.

Added sugars are sugars or caloric sweeteners added to foods or drinks during processing or preparation to add flavor or shelf life. They do not include natural sugars such as lactose in milk and fructose in fruits.

Researchers, led by Shan Yin, a urologist at Affiliated Hospital of North Sichuan Medical College, in Nanchong, China, compared the added-sugar intake by quartiles in the U.S. National Health and Nutrition Examination Survey 2007-2018.

A total of 28,303 adults were included in this study, with an average age of 48. Women who consumed less than 600 or more than 3,500 kcal or men who consumed less than 800 or more than 4,200 kcal were excluded.

Researchers adjusted for factors including age, race, education, income, physical activity, and marital, employment, and smoking status.

Compared with the first quartile of percentage added-sugar calorie intake, the population in the fourth quartile, with the highest added sugar intake, had a higher prevalence of kidney stones (odds ratio, 1.39; 95% confidence interval, 1.17-1.65).

Compared with the group with fewer than 5% of calories from added sugar, the group that consumed at least 25% of calories from added sugar had nearly twice the prevalence of kidney stones (OR, 1.88; 95% CI, 1.52-2.32).

Findings were published online in Frontiers in Nutrition.

“By identifying this association, policymakers and health professionals can emphasize the need for public health initiatives to reduce added sugar consumption and promote healthy dietary habits,” the authors write.
 

Added sugar in the U.S. diet

Sugar-sweetened beverages such as soft drinks and energy and sports drinks account for 34.4% of added sugars in the American diet. Previous studies have shown the relationship between consuming sugar-sweetened beverages and a higher risk of obesity, diabetes, and cardiovascular disease, diseases that often co-occur with kidney stones.

Researchers note that even though most added sugars in the United States come from sugar-sweetened beverages, it’s unclear whether the association between added sugars and kidney stones is caused by the beverages or other sources. For instance, fructose intake has been found to be independently associated with kidney stones.

How much is too much?

The recommended upper limit on added sugar is controversial and varies widely by health organization. The American Heart Association says daily average intake from added sugars should be no more than 150 kcal for adult males (about 9 teaspoons) and no more than 100 kcal for women (about 6 teaspoons). The Institute of Medicine allows up to 25% of calories to be consumed from added sugars. The 2020 Dietary Guidelines for Americans and World Health Organization set 10% of calories as the recommended upper limit.

Further investigating what causes kidney stones is critical as kidney stones are common worldwide, affecting about 1 in 10 people in the United States alone, and occurrence is increasing. Kidney stones have a high recurrence rate – about half of people who get them have a second episode within 10 years, the authors note.

The researchers acknowledge that because participants self-reported food intake, there is the potential for recall bias. Additionally, because of the cross-sectional design, the researchers were not able to determine whether sugar intake or kidney stone occurrence came first.

This work was supported by the Doctoral Fund Project of North Sichuan Medical College. The authors declare no relevant financial relationships.

Consuming a higher percentage of calories from added sugars is linked with a higher prevalence of kidney stones, new research suggests.

Though added sugars have been linked with multiple poor health outcomes, their link with kidney stones has been unclear.

Added sugars are sugars or caloric sweeteners added to foods or drinks during processing or preparation to add flavor or shelf life. They do not include natural sugars such as lactose in milk and fructose in fruits.

Researchers, led by Shan Yin, a urologist at Affiliated Hospital of North Sichuan Medical College, in Nanchong, China, compared the added-sugar intake by quartiles in the U.S. National Health and Nutrition Examination Survey 2007-2018.

A total of 28,303 adults were included in this study, with an average age of 48. Women who consumed less than 600 or more than 3,500 kcal or men who consumed less than 800 or more than 4,200 kcal were excluded.

Researchers adjusted for factors including age, race, education, income, physical activity, and marital, employment, and smoking status.

Compared with the first quartile of percentage added-sugar calorie intake, the population in the fourth quartile, with the highest added sugar intake, had a higher prevalence of kidney stones (odds ratio, 1.39; 95% confidence interval, 1.17-1.65).

Compared with the group with fewer than 5% of calories from added sugar, the group that consumed at least 25% of calories from added sugar had nearly twice the prevalence of kidney stones (OR, 1.88; 95% CI, 1.52-2.32).

Findings were published online in Frontiers in Nutrition.

“By identifying this association, policymakers and health professionals can emphasize the need for public health initiatives to reduce added sugar consumption and promote healthy dietary habits,” the authors write.
 

Added sugar in the U.S. diet

Sugar-sweetened beverages such as soft drinks and energy and sports drinks account for 34.4% of added sugars in the American diet. Previous studies have shown the relationship between consuming sugar-sweetened beverages and a higher risk of obesity, diabetes, and cardiovascular disease, diseases that often co-occur with kidney stones.

Researchers note that even though most added sugars in the United States come from sugar-sweetened beverages, it’s unclear whether the association between added sugars and kidney stones is caused by the beverages or other sources. For instance, fructose intake has been found to be independently associated with kidney stones.

How much is too much?

The recommended upper limit on added sugar is controversial and varies widely by health organization. The American Heart Association says daily average intake from added sugars should be no more than 150 kcal for adult males (about 9 teaspoons) and no more than 100 kcal for women (about 6 teaspoons). The Institute of Medicine allows up to 25% of calories to be consumed from added sugars. The 2020 Dietary Guidelines for Americans and World Health Organization set 10% of calories as the recommended upper limit.

Further investigating what causes kidney stones is critical as kidney stones are common worldwide, affecting about 1 in 10 people in the United States alone, and occurrence is increasing. Kidney stones have a high recurrence rate – about half of people who get them have a second episode within 10 years, the authors note.

The researchers acknowledge that because participants self-reported food intake, there is the potential for recall bias. Additionally, because of the cross-sectional design, the researchers were not able to determine whether sugar intake or kidney stone occurrence came first.

This work was supported by the Doctoral Fund Project of North Sichuan Medical College. The authors declare no relevant financial relationships.

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

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

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

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

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

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

TOPLINE:

A pilot study suggests that kombucha consumption reduces blood glucose levels in adults with type 2 diabetes. The sample size was too small for statistical significance.

blanaru/iStock/Getty Images

METHODOLOGY:

• Prospective, randomized, double-blinded, crossover study at a single-center urban hospital system.
• A total of 12 participants with type 2 diabetes were randomly assigned to consume 240 mL of either a kombucha product or placebo daily with dinner for 4 weeks.
• After an 8-week washout, they were switched to the other product for another 4 weeks.
• Fasting blood glucose levels were self-determined at baseline and at 1 and 4 weeks, and questionnaires were used to assess secondary health outcomes.
• Questionnaire data were analyzed for all 12 participants, but only 7 who completed the study were included in the analysis of fasting blood glucose.

TAKEAWAY:

• Kombucha significantly lowered average fasting blood glucose levels at week 4, compared with baseline (164 vs. 116 mg/dL; P = .035), while the placebo was not associated with statistically significant change (162 vs. 141 mg/dL; P = .078).
• Among just the five participants with baseline fasting glucose > 130 mg/dL, kombucha consumption was associated with a mean fasting blood glucose decrease of 74.3 mg/dL, significantly greater than the 15.9 mg/dL drop with placebo (P = .017).
• On cultural enumeration, the kombucha contained mostly lactic acid bacteria, acetic acid bacteria, and yeast, with molds present.

IN PRACTICE:

“Kombucha is a growing part of the beverage market in the United States and the world, driven, in part, by the wide range of suggested health benefits. However, nearly all of these benefits are based on in vitro or animal studies, and human clinical trials are needed to validate biological outcomes.”

SOURCE:

The study was conducted by Chagai Mendelson, of MedStar Georgetown University Hospital, Washington, and colleagues. It was published in Frontiers in Nutrition.

LIMITATIONS:

• The number of participants was small, and attrition was high.
• Glucose levels were self-reported.
• Only one kombucha was studied.

DISCLOSURES:

One author is a cofounder of Synbiotic Health and another has a financial interest in the company. The other authors have no disclosures. Kombucha and placebo drinks were donated by Craft Kombucha, but the company did not have access to the data, and no authors have financial ties with that company.

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

TOPLINE:

A pilot study suggests that kombucha consumption reduces blood glucose levels in adults with type 2 diabetes. The sample size was too small for statistical significance.

blanaru/iStock/Getty Images

METHODOLOGY:

• Prospective, randomized, double-blinded, crossover study at a single-center urban hospital system.
• A total of 12 participants with type 2 diabetes were randomly assigned to consume 240 mL of either a kombucha product or placebo daily with dinner for 4 weeks.
• After an 8-week washout, they were switched to the other product for another 4 weeks.
• Fasting blood glucose levels were self-determined at baseline and at 1 and 4 weeks, and questionnaires were used to assess secondary health outcomes.
• Questionnaire data were analyzed for all 12 participants, but only 7 who completed the study were included in the analysis of fasting blood glucose.

TAKEAWAY:

• Kombucha significantly lowered average fasting blood glucose levels at week 4, compared with baseline (164 vs. 116 mg/dL; P = .035), while the placebo was not associated with statistically significant change (162 vs. 141 mg/dL; P = .078).
• Among just the five participants with baseline fasting glucose > 130 mg/dL, kombucha consumption was associated with a mean fasting blood glucose decrease of 74.3 mg/dL, significantly greater than the 15.9 mg/dL drop with placebo (P = .017).
• On cultural enumeration, the kombucha contained mostly lactic acid bacteria, acetic acid bacteria, and yeast, with molds present.

IN PRACTICE:

“Kombucha is a growing part of the beverage market in the United States and the world, driven, in part, by the wide range of suggested health benefits. However, nearly all of these benefits are based on in vitro or animal studies, and human clinical trials are needed to validate biological outcomes.”

SOURCE:

The study was conducted by Chagai Mendelson, of MedStar Georgetown University Hospital, Washington, and colleagues. It was published in Frontiers in Nutrition.

LIMITATIONS:

• The number of participants was small, and attrition was high.
• Glucose levels were self-reported.
• Only one kombucha was studied.

DISCLOSURES:

One author is a cofounder of Synbiotic Health and another has a financial interest in the company. The other authors have no disclosures. Kombucha and placebo drinks were donated by Craft Kombucha, but the company did not have access to the data, and no authors have financial ties with that company.

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

TOPLINE:

A pilot study suggests that kombucha consumption reduces blood glucose levels in adults with type 2 diabetes. The sample size was too small for statistical significance.

blanaru/iStock/Getty Images

METHODOLOGY:

• Prospective, randomized, double-blinded, crossover study at a single-center urban hospital system.
• A total of 12 participants with type 2 diabetes were randomly assigned to consume 240 mL of either a kombucha product or placebo daily with dinner for 4 weeks.
• After an 8-week washout, they were switched to the other product for another 4 weeks.
• Fasting blood glucose levels were self-determined at baseline and at 1 and 4 weeks, and questionnaires were used to assess secondary health outcomes.
• Questionnaire data were analyzed for all 12 participants, but only 7 who completed the study were included in the analysis of fasting blood glucose.

TAKEAWAY:

• Kombucha significantly lowered average fasting blood glucose levels at week 4, compared with baseline (164 vs. 116 mg/dL; P = .035), while the placebo was not associated with statistically significant change (162 vs. 141 mg/dL; P = .078).
• Among just the five participants with baseline fasting glucose > 130 mg/dL, kombucha consumption was associated with a mean fasting blood glucose decrease of 74.3 mg/dL, significantly greater than the 15.9 mg/dL drop with placebo (P = .017).
• On cultural enumeration, the kombucha contained mostly lactic acid bacteria, acetic acid bacteria, and yeast, with molds present.

IN PRACTICE:

“Kombucha is a growing part of the beverage market in the United States and the world, driven, in part, by the wide range of suggested health benefits. However, nearly all of these benefits are based on in vitro or animal studies, and human clinical trials are needed to validate biological outcomes.”

SOURCE:

The study was conducted by Chagai Mendelson, of MedStar Georgetown University Hospital, Washington, and colleagues. It was published in Frontiers in Nutrition.

LIMITATIONS:

• The number of participants was small, and attrition was high.
• Glucose levels were self-reported.
• Only one kombucha was studied.

DISCLOSURES:

One author is a cofounder of Synbiotic Health and another has a financial interest in the company. The other authors have no disclosures. Kombucha and placebo drinks were donated by Craft Kombucha, but the company did not have access to the data, and no authors have financial ties with that company.

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

A new discovery of differences between the eyes of people with and without diabetes could point to new approaches for treating diabetic keratopathy, as well as other diabetes-related wound healing problems.

Vision loss caused by diabetes arises primarily from retinopathy, but up to 70% of people with diabetes also experience corneal problems, including keratopathy and neuropathy. Diabetic keratopathy involves impairments in epithelial wound healing, barrier function, and tear production, along with epithelial erosions and keratitis. As a result, the cornea may heal more slowly and less completely following an injury or procedures such as cataract surgery or laser therapy for diabetic retinopathy.

The abnormal wound healing is caused by impaired limbal epithelial stem cells, and the new research, published online in Diabetologia, involved isolation of those cells from 30 donor eyes of humans with and 23 without diabetes. Significant differences were found in DNA methylation between the cells of those two groups. Specifically, the WNT5A gene was hypermethylated at the promotor region in the diabetic cells and its protein markedly repressed.

However, treatment with various approaches, including exogenous WNT5A methylation inhibitors and a nanoconjugate that inhibits WNT5A suppression, improved corneal epithelial wound healing as well as expression of the limbic epithelial stem cells.

“Overall, [the] Wnt-5a [protein] is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea,” wrote Ruchi Shah, PhD, of the Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, and colleagues.

The finding represents more cellular changes than researchers had previously been aware of, study senior author Alexander Ljubimov, PhD, DSc, director of the eye program at the Institute, said in a statement.

“The discovery does not affect gene sequence but entails specific DNA modifications altering gene expression – what are known as epigenetic alterations,” he said.

In the experiments, treatment of the impaired diabetic limbal epithelial cells with the exogenous Wnt-5a accelerated wound healing by 1.4-fold (P < .05), compared with untreated cells and reduced healing time in diabetic organ-ultured corneas by 37% (P < .05).

Treatment with the DNA methylation inhibitor zebularine also increased levels of Wnt-5a in the diabetic limbic epithelial cells by 37% (P < .01), dose-dependently stimulated wound healing by 60% at 24 hours (P < .01), and improved wound healing by 30% in diabetic organ-cultured corneas.

The finding of Wnt-5a as a new diabetic corneal marker regulating wound healing and stem cell function may have implications for other diabetes complications involving impaired wound healing, including diabetic foot ulcers, as they share similar neurovascular, sensory, and immunological compromise with diabetic eye disease, Dr. Shah and colleagues wrote.

“Novel therapies to reverse both types of epigenetic silencing could benefit corneal function and may also prove to be beneficial in other wound healing–related diabetic complications,” they wrote.

The investigators are now working on combination therapies that target both mRNA and DNA methylation in hopes of obtaining even better wound healing.

“Our goal is to develop topical, sustained-release drugs for corneal wound healing,” said Dr. Ljubimov. “Drugs that are [Food and Drug Administration] approved and could be easily applied may be one of the most promising approaches for effective future therapies.”

This work was funded by the National Institutes of Health and the Cedars-Sinai Board of Governors Regenerative Medicine Institute. The authors reported no further disclosures.

A version of this article appeared on Medscape.com.

A new discovery of differences between the eyes of people with and without diabetes could point to new approaches for treating diabetic keratopathy, as well as other diabetes-related wound healing problems.

Vision loss caused by diabetes arises primarily from retinopathy, but up to 70% of people with diabetes also experience corneal problems, including keratopathy and neuropathy. Diabetic keratopathy involves impairments in epithelial wound healing, barrier function, and tear production, along with epithelial erosions and keratitis. As a result, the cornea may heal more slowly and less completely following an injury or procedures such as cataract surgery or laser therapy for diabetic retinopathy.

The abnormal wound healing is caused by impaired limbal epithelial stem cells, and the new research, published online in Diabetologia, involved isolation of those cells from 30 donor eyes of humans with and 23 without diabetes. Significant differences were found in DNA methylation between the cells of those two groups. Specifically, the WNT5A gene was hypermethylated at the promotor region in the diabetic cells and its protein markedly repressed.

However, treatment with various approaches, including exogenous WNT5A methylation inhibitors and a nanoconjugate that inhibits WNT5A suppression, improved corneal epithelial wound healing as well as expression of the limbic epithelial stem cells.

“Overall, [the] Wnt-5a [protein] is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea,” wrote Ruchi Shah, PhD, of the Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, and colleagues.

The finding represents more cellular changes than researchers had previously been aware of, study senior author Alexander Ljubimov, PhD, DSc, director of the eye program at the Institute, said in a statement.

“The discovery does not affect gene sequence but entails specific DNA modifications altering gene expression – what are known as epigenetic alterations,” he said.

In the experiments, treatment of the impaired diabetic limbal epithelial cells with the exogenous Wnt-5a accelerated wound healing by 1.4-fold (P < .05), compared with untreated cells and reduced healing time in diabetic organ-ultured corneas by 37% (P < .05).

Treatment with the DNA methylation inhibitor zebularine also increased levels of Wnt-5a in the diabetic limbic epithelial cells by 37% (P < .01), dose-dependently stimulated wound healing by 60% at 24 hours (P < .01), and improved wound healing by 30% in diabetic organ-cultured corneas.

The finding of Wnt-5a as a new diabetic corneal marker regulating wound healing and stem cell function may have implications for other diabetes complications involving impaired wound healing, including diabetic foot ulcers, as they share similar neurovascular, sensory, and immunological compromise with diabetic eye disease, Dr. Shah and colleagues wrote.

“Novel therapies to reverse both types of epigenetic silencing could benefit corneal function and may also prove to be beneficial in other wound healing–related diabetic complications,” they wrote.

The investigators are now working on combination therapies that target both mRNA and DNA methylation in hopes of obtaining even better wound healing.

“Our goal is to develop topical, sustained-release drugs for corneal wound healing,” said Dr. Ljubimov. “Drugs that are [Food and Drug Administration] approved and could be easily applied may be one of the most promising approaches for effective future therapies.”

This work was funded by the National Institutes of Health and the Cedars-Sinai Board of Governors Regenerative Medicine Institute. The authors reported no further disclosures.

A version of this article appeared on Medscape.com.

A new discovery of differences between the eyes of people with and without diabetes could point to new approaches for treating diabetic keratopathy, as well as other diabetes-related wound healing problems.

Vision loss caused by diabetes arises primarily from retinopathy, but up to 70% of people with diabetes also experience corneal problems, including keratopathy and neuropathy. Diabetic keratopathy involves impairments in epithelial wound healing, barrier function, and tear production, along with epithelial erosions and keratitis. As a result, the cornea may heal more slowly and less completely following an injury or procedures such as cataract surgery or laser therapy for diabetic retinopathy.

The abnormal wound healing is caused by impaired limbal epithelial stem cells, and the new research, published online in Diabetologia, involved isolation of those cells from 30 donor eyes of humans with and 23 without diabetes. Significant differences were found in DNA methylation between the cells of those two groups. Specifically, the WNT5A gene was hypermethylated at the promotor region in the diabetic cells and its protein markedly repressed.

However, treatment with various approaches, including exogenous WNT5A methylation inhibitors and a nanoconjugate that inhibits WNT5A suppression, improved corneal epithelial wound healing as well as expression of the limbic epithelial stem cells.

“Overall, [the] Wnt-5a [protein] is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea,” wrote Ruchi Shah, PhD, of the Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, and colleagues.

The finding represents more cellular changes than researchers had previously been aware of, study senior author Alexander Ljubimov, PhD, DSc, director of the eye program at the Institute, said in a statement.

“The discovery does not affect gene sequence but entails specific DNA modifications altering gene expression – what are known as epigenetic alterations,” he said.

In the experiments, treatment of the impaired diabetic limbal epithelial cells with the exogenous Wnt-5a accelerated wound healing by 1.4-fold (P < .05), compared with untreated cells and reduced healing time in diabetic organ-ultured corneas by 37% (P < .05).

Treatment with the DNA methylation inhibitor zebularine also increased levels of Wnt-5a in the diabetic limbic epithelial cells by 37% (P < .01), dose-dependently stimulated wound healing by 60% at 24 hours (P < .01), and improved wound healing by 30% in diabetic organ-cultured corneas.

The finding of Wnt-5a as a new diabetic corneal marker regulating wound healing and stem cell function may have implications for other diabetes complications involving impaired wound healing, including diabetic foot ulcers, as they share similar neurovascular, sensory, and immunological compromise with diabetic eye disease, Dr. Shah and colleagues wrote.

“Novel therapies to reverse both types of epigenetic silencing could benefit corneal function and may also prove to be beneficial in other wound healing–related diabetic complications,” they wrote.

The investigators are now working on combination therapies that target both mRNA and DNA methylation in hopes of obtaining even better wound healing.

“Our goal is to develop topical, sustained-release drugs for corneal wound healing,” said Dr. Ljubimov. “Drugs that are [Food and Drug Administration] approved and could be easily applied may be one of the most promising approaches for effective future therapies.”

This work was funded by the National Institutes of Health and the Cedars-Sinai Board of Governors Regenerative Medicine Institute. The authors reported no further disclosures.

A version of this article appeared on Medscape.com.