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Anti-Rheumatic Drugs Linked to Reduced Thyroid Disease Incidence
TOPLINE:
Patients with rheumatoid arthritis (RA) in a large Swedish population cohort show a reduced incidence of autoimmune thyroid diseases, such as hypothyroidism or hyperthyroidism, after being diagnosed with RA, with the effect being more pronounced among those treated with disease-modifying anti-rheumatic drugs (DMARDs), particularly TNF-inhibitors.
Although DMARDs are commonly used in the treatment of RA, the drugs are rarely used to treat autoimmune thyroid diseases. The new results support theories raised in previous smaller studies that DMARDs could have a protective effect against thyroid disease.
METHODOLOGY:
- The study involved 13,731 patients with new-onset RA who were listed in the Swedish Rheumatology Quality Register between 2006 and 2018.
- The patients were matched for sex, age, and residential area with up to five reference individuals in the general population of 63,201 comparators.
- Overall, patients with RA were 64.7% female, with a mean age of 59. They were followed up with their matched comparators until the development of autoimmune thyroid disease, death, emigration, or the end of the study period, December 2019.
- The relative risks of autoimmune thyroid disease following a diagnosis of RA and with treatment with DMARDs were compared with those risks in the general population.
- Participants with a non-autoimmune cause for thyroxine prescription were excluded, as were those with an autoimmune thyroid disease at the time of RA diagnosis.
TAKEAWAY:
- Following their RA diagnosis, 321 (2.3%) of patients developed an autoimmune thyroid disease, compared with 1838 (2.9%) in the general population comparators, representing an incidence of 3.7 vs 4.6 per 1000 person-years (hazard ratio [HR], 0.81).
- The lower incidence of autoimmune thyroid disease was more pronounced with longer RA duration. For instance, at 10-14 years after an RA diagnosis, the incidence was 2.9 vs. 4.5 autoimmune thyroid disease events per 1000 person-years, respectively (HR, 0.64).
- The decreased risk of incident autoimmune thyroid disease among RA patients compared with the general population was strongest among patients treated with biologic DMARDs (bDMARD), with an HR of 0.54.
- The reduced incidence of autoimmune thyroid disease with bDMARD use was most pronounced among users of TNF-inhibitors (HR, 0.67).
- The lower incidence of autoimmune thyroid disease following a diagnosis of RA contrasts with previous studies showing an increased risk for thyroid disease associated with RA.
- However, the decreased risk of thyroid disease following bDMARD treatment supports the theory that immunomodulatory treatment could also have an effect of blunting the inflammatory processes that can lead to overt clinical autoimmune thyroid disease.
IN PRACTICE:
“To our knowledge, no previous study has investigated whether the risk of new-onset autoimmune thyroid disease is affected by RA treatment in early RA,” the authors report.
“Our results demonstrate that compared to the general population, patients with RA treated with bDMARDs, TNF-inhibitors in particular, are at decreased risk of developing autoimmune thyroid disease, a finding that calls for replication and may open for drug-repurposing studies,” they note.
SOURCE:
The study was conducted by first author Kristin Waldenlind, PhD, of the Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden, and colleagues. It was published online November 27 in the Journal of Internal Medicine.
LIMITATIONS:
The study lacked details on participants’ thyroid autoantibody and hormone levels.
The presence of autoimmune thyroid disease was determined based on prescriptions for thyroxine, hence the authors cannot exclude the possibility of a lower threshold for thyroxine prescription among patients treated with DMARDs.
Information was not available on potential risk factors for RA and autoimmune thyroid disease that might have introduced confounding, such as smoking or obesity.
DISCLOSURES:
The study received funding from the Swedish Research Council, the Swedish Heart Lung Foundation, Vinnova, and Region Stockholm/Karolinska Institutet (ALF). The authors’ disclosures are detailed in the published study.
A version of this article appeared on Medscape.com.
TOPLINE:
Patients with rheumatoid arthritis (RA) in a large Swedish population cohort show a reduced incidence of autoimmune thyroid diseases, such as hypothyroidism or hyperthyroidism, after being diagnosed with RA, with the effect being more pronounced among those treated with disease-modifying anti-rheumatic drugs (DMARDs), particularly TNF-inhibitors.
Although DMARDs are commonly used in the treatment of RA, the drugs are rarely used to treat autoimmune thyroid diseases. The new results support theories raised in previous smaller studies that DMARDs could have a protective effect against thyroid disease.
METHODOLOGY:
- The study involved 13,731 patients with new-onset RA who were listed in the Swedish Rheumatology Quality Register between 2006 and 2018.
- The patients were matched for sex, age, and residential area with up to five reference individuals in the general population of 63,201 comparators.
- Overall, patients with RA were 64.7% female, with a mean age of 59. They were followed up with their matched comparators until the development of autoimmune thyroid disease, death, emigration, or the end of the study period, December 2019.
- The relative risks of autoimmune thyroid disease following a diagnosis of RA and with treatment with DMARDs were compared with those risks in the general population.
- Participants with a non-autoimmune cause for thyroxine prescription were excluded, as were those with an autoimmune thyroid disease at the time of RA diagnosis.
TAKEAWAY:
- Following their RA diagnosis, 321 (2.3%) of patients developed an autoimmune thyroid disease, compared with 1838 (2.9%) in the general population comparators, representing an incidence of 3.7 vs 4.6 per 1000 person-years (hazard ratio [HR], 0.81).
- The lower incidence of autoimmune thyroid disease was more pronounced with longer RA duration. For instance, at 10-14 years after an RA diagnosis, the incidence was 2.9 vs. 4.5 autoimmune thyroid disease events per 1000 person-years, respectively (HR, 0.64).
- The decreased risk of incident autoimmune thyroid disease among RA patients compared with the general population was strongest among patients treated with biologic DMARDs (bDMARD), with an HR of 0.54.
- The reduced incidence of autoimmune thyroid disease with bDMARD use was most pronounced among users of TNF-inhibitors (HR, 0.67).
- The lower incidence of autoimmune thyroid disease following a diagnosis of RA contrasts with previous studies showing an increased risk for thyroid disease associated with RA.
- However, the decreased risk of thyroid disease following bDMARD treatment supports the theory that immunomodulatory treatment could also have an effect of blunting the inflammatory processes that can lead to overt clinical autoimmune thyroid disease.
IN PRACTICE:
“To our knowledge, no previous study has investigated whether the risk of new-onset autoimmune thyroid disease is affected by RA treatment in early RA,” the authors report.
“Our results demonstrate that compared to the general population, patients with RA treated with bDMARDs, TNF-inhibitors in particular, are at decreased risk of developing autoimmune thyroid disease, a finding that calls for replication and may open for drug-repurposing studies,” they note.
SOURCE:
The study was conducted by first author Kristin Waldenlind, PhD, of the Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden, and colleagues. It was published online November 27 in the Journal of Internal Medicine.
LIMITATIONS:
The study lacked details on participants’ thyroid autoantibody and hormone levels.
The presence of autoimmune thyroid disease was determined based on prescriptions for thyroxine, hence the authors cannot exclude the possibility of a lower threshold for thyroxine prescription among patients treated with DMARDs.
Information was not available on potential risk factors for RA and autoimmune thyroid disease that might have introduced confounding, such as smoking or obesity.
DISCLOSURES:
The study received funding from the Swedish Research Council, the Swedish Heart Lung Foundation, Vinnova, and Region Stockholm/Karolinska Institutet (ALF). The authors’ disclosures are detailed in the published study.
A version of this article appeared on Medscape.com.
TOPLINE:
Patients with rheumatoid arthritis (RA) in a large Swedish population cohort show a reduced incidence of autoimmune thyroid diseases, such as hypothyroidism or hyperthyroidism, after being diagnosed with RA, with the effect being more pronounced among those treated with disease-modifying anti-rheumatic drugs (DMARDs), particularly TNF-inhibitors.
Although DMARDs are commonly used in the treatment of RA, the drugs are rarely used to treat autoimmune thyroid diseases. The new results support theories raised in previous smaller studies that DMARDs could have a protective effect against thyroid disease.
METHODOLOGY:
- The study involved 13,731 patients with new-onset RA who were listed in the Swedish Rheumatology Quality Register between 2006 and 2018.
- The patients were matched for sex, age, and residential area with up to five reference individuals in the general population of 63,201 comparators.
- Overall, patients with RA were 64.7% female, with a mean age of 59. They were followed up with their matched comparators until the development of autoimmune thyroid disease, death, emigration, or the end of the study period, December 2019.
- The relative risks of autoimmune thyroid disease following a diagnosis of RA and with treatment with DMARDs were compared with those risks in the general population.
- Participants with a non-autoimmune cause for thyroxine prescription were excluded, as were those with an autoimmune thyroid disease at the time of RA diagnosis.
TAKEAWAY:
- Following their RA diagnosis, 321 (2.3%) of patients developed an autoimmune thyroid disease, compared with 1838 (2.9%) in the general population comparators, representing an incidence of 3.7 vs 4.6 per 1000 person-years (hazard ratio [HR], 0.81).
- The lower incidence of autoimmune thyroid disease was more pronounced with longer RA duration. For instance, at 10-14 years after an RA diagnosis, the incidence was 2.9 vs. 4.5 autoimmune thyroid disease events per 1000 person-years, respectively (HR, 0.64).
- The decreased risk of incident autoimmune thyroid disease among RA patients compared with the general population was strongest among patients treated with biologic DMARDs (bDMARD), with an HR of 0.54.
- The reduced incidence of autoimmune thyroid disease with bDMARD use was most pronounced among users of TNF-inhibitors (HR, 0.67).
- The lower incidence of autoimmune thyroid disease following a diagnosis of RA contrasts with previous studies showing an increased risk for thyroid disease associated with RA.
- However, the decreased risk of thyroid disease following bDMARD treatment supports the theory that immunomodulatory treatment could also have an effect of blunting the inflammatory processes that can lead to overt clinical autoimmune thyroid disease.
IN PRACTICE:
“To our knowledge, no previous study has investigated whether the risk of new-onset autoimmune thyroid disease is affected by RA treatment in early RA,” the authors report.
“Our results demonstrate that compared to the general population, patients with RA treated with bDMARDs, TNF-inhibitors in particular, are at decreased risk of developing autoimmune thyroid disease, a finding that calls for replication and may open for drug-repurposing studies,” they note.
SOURCE:
The study was conducted by first author Kristin Waldenlind, PhD, of the Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden, and colleagues. It was published online November 27 in the Journal of Internal Medicine.
LIMITATIONS:
The study lacked details on participants’ thyroid autoantibody and hormone levels.
The presence of autoimmune thyroid disease was determined based on prescriptions for thyroxine, hence the authors cannot exclude the possibility of a lower threshold for thyroxine prescription among patients treated with DMARDs.
Information was not available on potential risk factors for RA and autoimmune thyroid disease that might have introduced confounding, such as smoking or obesity.
DISCLOSURES:
The study received funding from the Swedish Research Council, the Swedish Heart Lung Foundation, Vinnova, and Region Stockholm/Karolinska Institutet (ALF). The authors’ disclosures are detailed in the published study.
A version of this article appeared on Medscape.com.
Already-available drug could help treat type 1 diabetes
“I think we have lots of potential to improve people’s quality of life who are living with type 1 diabetes if we can increase their endogenous insulin secretion. ... I think long-term combination therapy is going to be the answer,” study author Emily K. Sims, MD, a pediatric endocrinologist at Indiana University, Indianapolis, said in an interview.
DFMO inhibits the polyamine biosynthesis pathway, which plays a role in the inflammatory responses in autoimmune diseases, including type 1 diabetes. It’s sold under the name eflornithine as an intravenous treatment for African sleeping sickness (trypanosomiasis) and as a cream for unwanted hair growth in women. It also has orphan designations for treating various cancers, including neuroblastoma.
In type 1 diabetes, the immune system destroys insulin-producing pancreatic beta cells. Insulin treatment is required. Recently, the monoclonal antibody teplizumab (Tzield, Sanofi) was approved as a treatment for delaying the onset of type 1 diabetes in people with autoantibodies that signify a preclinical stage of the condition. As yet, no agent has been approved for preserving beta-cell function after the onset of type 1 diabetes, but many are under investigation.
The new safety study by Dr. Sims and colleagues, which was published in Cell Medicine Reports, enrolled 41 people with type 1 diabetes who had been diagnosed within the previous 8 months, including 31 children. Participants were randomly assigned to undergo oral treatment with DFMO at one of five doses or placebo for 3 months, with 3 additional months of follow-up.
Following a mixed-meal tolerance test at 6 months, the C-peptide area under the curve – a measure of beta-cell function – was significantly higher with the three highest DFMO doses compared to placebo (P = .02, .03, and .02 for 125 mg/m2, 750 mg/m2, and 1,000 mg/m2, respectively).
Two individuals dropped out, one because of anaphylaxis. There were no dose-limiting toxicities or serious adverse events, while mild gastrointestinal events, anemia, and headache were common. “Although there’s no [Food and Drug Administration] approval for the oral form right now, there’s a lot of safety data, including in kids from the neuroblastoma studies,” Dr. Sims explained.
There were no differences in C-peptide at 3 months or in hemoglobin A1c at any time point. Glucose areas under the curve were significantly lower for DFMO, compared with placebo in the 125-mg/m2 and 750-mg/m2 treatment groups at the 6-month time point (P = .03 and .04, respectively).
In their article, Dr. Sims and colleagues also reported confirmatory analyses in mice, as well as testing in the humans showing that there didn’t appear to be significant immune system modulation. “So, we can envision giving DFMO in addition to something that targets the immune system, as a combination therapy,” said Dr. Sims, who also worked on the pivotal study of teplizumab.
“I’m excited. The sample size is small, so I was kind of expecting no efficacy signals. ... It’s definitely worth following up,” she said.
However, she noted, “it wasn’t a slam-dunk huge effect. It was subtle. It seemed that things were kind of more stable compared to placebo over time versus ... a big increase in C-peptide over time.”
But, she added, “I believe that even teplizumab will need to be used in combination. It delays the onset of type 1 diabetes and improves C-peptide, but it didn’t get everyone off insulin. I don’t think we’ve seen any drug that won’t need to be used in combination.”
Dr. Sims pointed to other investigational agents, such as verapamil and various Janus kinase inhibitors, that may also serve in combination to forestall or reduce insulin dependency for people with either new-onset type 1 diabetes or those who have been identified via screening as having type 1 diabetes–related autoantibodies. “I think there are a lot of potential different interventions.”
Dr. Sims and colleagues are now conducting a larger six-center JDRF-funded study of DFMO in early-onset type 1 diabetes that will be fully powered and that will use the highest tolerated doses from the preliminary study.
She believes there will likely be benefit even if the agent doesn’t completely reverse the disease. “The people who are making more insulin are just easier to manage, with more time in range and less hypoglycemia.” Even if the drugs only delay but don’t prevent type 1 diabetes entirely in those at risk, “the improvement in quality of life of being able to delay insulin for a few years is really palpable. ... I’m really optimistic.”
Dr. Sims disclosed no relevant financial relationships. Three other authors are coauthors on a patent application for the use of DFMO for the treatment of beta-cell dysfunction in type 1 diabetes; one of those three authors is an employee of Cancer Prevention Pharmaceuticals.
A version of this article first appeared on Medscape.com.
“I think we have lots of potential to improve people’s quality of life who are living with type 1 diabetes if we can increase their endogenous insulin secretion. ... I think long-term combination therapy is going to be the answer,” study author Emily K. Sims, MD, a pediatric endocrinologist at Indiana University, Indianapolis, said in an interview.
DFMO inhibits the polyamine biosynthesis pathway, which plays a role in the inflammatory responses in autoimmune diseases, including type 1 diabetes. It’s sold under the name eflornithine as an intravenous treatment for African sleeping sickness (trypanosomiasis) and as a cream for unwanted hair growth in women. It also has orphan designations for treating various cancers, including neuroblastoma.
In type 1 diabetes, the immune system destroys insulin-producing pancreatic beta cells. Insulin treatment is required. Recently, the monoclonal antibody teplizumab (Tzield, Sanofi) was approved as a treatment for delaying the onset of type 1 diabetes in people with autoantibodies that signify a preclinical stage of the condition. As yet, no agent has been approved for preserving beta-cell function after the onset of type 1 diabetes, but many are under investigation.
The new safety study by Dr. Sims and colleagues, which was published in Cell Medicine Reports, enrolled 41 people with type 1 diabetes who had been diagnosed within the previous 8 months, including 31 children. Participants were randomly assigned to undergo oral treatment with DFMO at one of five doses or placebo for 3 months, with 3 additional months of follow-up.
Following a mixed-meal tolerance test at 6 months, the C-peptide area under the curve – a measure of beta-cell function – was significantly higher with the three highest DFMO doses compared to placebo (P = .02, .03, and .02 for 125 mg/m2, 750 mg/m2, and 1,000 mg/m2, respectively).
Two individuals dropped out, one because of anaphylaxis. There were no dose-limiting toxicities or serious adverse events, while mild gastrointestinal events, anemia, and headache were common. “Although there’s no [Food and Drug Administration] approval for the oral form right now, there’s a lot of safety data, including in kids from the neuroblastoma studies,” Dr. Sims explained.
There were no differences in C-peptide at 3 months or in hemoglobin A1c at any time point. Glucose areas under the curve were significantly lower for DFMO, compared with placebo in the 125-mg/m2 and 750-mg/m2 treatment groups at the 6-month time point (P = .03 and .04, respectively).
In their article, Dr. Sims and colleagues also reported confirmatory analyses in mice, as well as testing in the humans showing that there didn’t appear to be significant immune system modulation. “So, we can envision giving DFMO in addition to something that targets the immune system, as a combination therapy,” said Dr. Sims, who also worked on the pivotal study of teplizumab.
“I’m excited. The sample size is small, so I was kind of expecting no efficacy signals. ... It’s definitely worth following up,” she said.
However, she noted, “it wasn’t a slam-dunk huge effect. It was subtle. It seemed that things were kind of more stable compared to placebo over time versus ... a big increase in C-peptide over time.”
But, she added, “I believe that even teplizumab will need to be used in combination. It delays the onset of type 1 diabetes and improves C-peptide, but it didn’t get everyone off insulin. I don’t think we’ve seen any drug that won’t need to be used in combination.”
Dr. Sims pointed to other investigational agents, such as verapamil and various Janus kinase inhibitors, that may also serve in combination to forestall or reduce insulin dependency for people with either new-onset type 1 diabetes or those who have been identified via screening as having type 1 diabetes–related autoantibodies. “I think there are a lot of potential different interventions.”
Dr. Sims and colleagues are now conducting a larger six-center JDRF-funded study of DFMO in early-onset type 1 diabetes that will be fully powered and that will use the highest tolerated doses from the preliminary study.
She believes there will likely be benefit even if the agent doesn’t completely reverse the disease. “The people who are making more insulin are just easier to manage, with more time in range and less hypoglycemia.” Even if the drugs only delay but don’t prevent type 1 diabetes entirely in those at risk, “the improvement in quality of life of being able to delay insulin for a few years is really palpable. ... I’m really optimistic.”
Dr. Sims disclosed no relevant financial relationships. Three other authors are coauthors on a patent application for the use of DFMO for the treatment of beta-cell dysfunction in type 1 diabetes; one of those three authors is an employee of Cancer Prevention Pharmaceuticals.
A version of this article first appeared on Medscape.com.
“I think we have lots of potential to improve people’s quality of life who are living with type 1 diabetes if we can increase their endogenous insulin secretion. ... I think long-term combination therapy is going to be the answer,” study author Emily K. Sims, MD, a pediatric endocrinologist at Indiana University, Indianapolis, said in an interview.
DFMO inhibits the polyamine biosynthesis pathway, which plays a role in the inflammatory responses in autoimmune diseases, including type 1 diabetes. It’s sold under the name eflornithine as an intravenous treatment for African sleeping sickness (trypanosomiasis) and as a cream for unwanted hair growth in women. It also has orphan designations for treating various cancers, including neuroblastoma.
In type 1 diabetes, the immune system destroys insulin-producing pancreatic beta cells. Insulin treatment is required. Recently, the monoclonal antibody teplizumab (Tzield, Sanofi) was approved as a treatment for delaying the onset of type 1 diabetes in people with autoantibodies that signify a preclinical stage of the condition. As yet, no agent has been approved for preserving beta-cell function after the onset of type 1 diabetes, but many are under investigation.
The new safety study by Dr. Sims and colleagues, which was published in Cell Medicine Reports, enrolled 41 people with type 1 diabetes who had been diagnosed within the previous 8 months, including 31 children. Participants were randomly assigned to undergo oral treatment with DFMO at one of five doses or placebo for 3 months, with 3 additional months of follow-up.
Following a mixed-meal tolerance test at 6 months, the C-peptide area under the curve – a measure of beta-cell function – was significantly higher with the three highest DFMO doses compared to placebo (P = .02, .03, and .02 for 125 mg/m2, 750 mg/m2, and 1,000 mg/m2, respectively).
Two individuals dropped out, one because of anaphylaxis. There were no dose-limiting toxicities or serious adverse events, while mild gastrointestinal events, anemia, and headache were common. “Although there’s no [Food and Drug Administration] approval for the oral form right now, there’s a lot of safety data, including in kids from the neuroblastoma studies,” Dr. Sims explained.
There were no differences in C-peptide at 3 months or in hemoglobin A1c at any time point. Glucose areas under the curve were significantly lower for DFMO, compared with placebo in the 125-mg/m2 and 750-mg/m2 treatment groups at the 6-month time point (P = .03 and .04, respectively).
In their article, Dr. Sims and colleagues also reported confirmatory analyses in mice, as well as testing in the humans showing that there didn’t appear to be significant immune system modulation. “So, we can envision giving DFMO in addition to something that targets the immune system, as a combination therapy,” said Dr. Sims, who also worked on the pivotal study of teplizumab.
“I’m excited. The sample size is small, so I was kind of expecting no efficacy signals. ... It’s definitely worth following up,” she said.
However, she noted, “it wasn’t a slam-dunk huge effect. It was subtle. It seemed that things were kind of more stable compared to placebo over time versus ... a big increase in C-peptide over time.”
But, she added, “I believe that even teplizumab will need to be used in combination. It delays the onset of type 1 diabetes and improves C-peptide, but it didn’t get everyone off insulin. I don’t think we’ve seen any drug that won’t need to be used in combination.”
Dr. Sims pointed to other investigational agents, such as verapamil and various Janus kinase inhibitors, that may also serve in combination to forestall or reduce insulin dependency for people with either new-onset type 1 diabetes or those who have been identified via screening as having type 1 diabetes–related autoantibodies. “I think there are a lot of potential different interventions.”
Dr. Sims and colleagues are now conducting a larger six-center JDRF-funded study of DFMO in early-onset type 1 diabetes that will be fully powered and that will use the highest tolerated doses from the preliminary study.
She believes there will likely be benefit even if the agent doesn’t completely reverse the disease. “The people who are making more insulin are just easier to manage, with more time in range and less hypoglycemia.” Even if the drugs only delay but don’t prevent type 1 diabetes entirely in those at risk, “the improvement in quality of life of being able to delay insulin for a few years is really palpable. ... I’m really optimistic.”
Dr. Sims disclosed no relevant financial relationships. Three other authors are coauthors on a patent application for the use of DFMO for the treatment of beta-cell dysfunction in type 1 diabetes; one of those three authors is an employee of Cancer Prevention Pharmaceuticals.
A version of this article first appeared on Medscape.com.
FROM CELL MEDICINE REPORTS
Sleeping beats sitting? What a new study means for your patients
Sit less, move more. Or stand more. Or sleep more.
Replacing 30 minutes of sitting a day with equal time standing or even sleeping could improve obesity markers like body weight and waist circumference, according to a new cross-sectional study investigating the impact of movement behavior on cardiometabolic health.
The findings suggest that, while higher-intensity activity may confer benefits sooner, adding more light activity or more standing, or even going to bed earlier, could improve heart health measures over time.
“Our study highlights that replacing sedentary behavior with any other behavior can be beneficial,” said study author Joanna M. Blodgett, PhD, a researcher at University College London’s Institute of Sport, Exercise and Health, and department of targeted intervention.
The study builds on a large and growing body of evidence that movement behaviors impact cardiometabolic health. Increasing physical activity to 150 minutes a week has been shown to reduce the risk for cardiovascular disease by 17% and type 2 diabetes by 26%. Other studies suggest that even modest increases in physical activity can be beneficial. A prospective study published in October found that even short activity bouts of a few minutes a day may lower risks for heart attack, stroke, and early death.
In the new study, researchers analyzed data from six studies and more than 15,000 participants, ranking behaviors according to their association with heart health. Moderate-to-vigorous activity was linked to the greatest benefit, followed by light activity, standing, sleeping, and finally – dead last on the list – sitting.
A thigh-worn device tracked participants’ activity throughout the day, and six measures gauged heart health: body mass index (BMI), waist circumference, HDL cholesterol, total-cholesterol-to-HDL ratio, triglycerides, and glycated hemoglobin.
Researchers modeled what would happen if people swapped various amounts of one activity for another every day for a week. Replacing just 4-13 minutes of sitting with moderate to vigorous activity improved heart health markers.
The cardiovascular demands of regular intense activity like running, cycling, dancing, or playing sports – even in small bouts – strengthen the heart and improve blood flow throughout the body, Dr. Blodgett said. “This can lower cholesterol, blood pressure, and resting heart rate.”
Even if adding moderate to vigorous activity is not an option, the findings suggest that people can still see benefits by replacing sitting with virtually any other activity – walking, standing, even sleeping.
Limitations
Because the study was observational, results can’t be used to infer causality.
“We cannot directly lean on the study results to guide prescriptions for particular exercise or lifestyle changes,” said Matthew Tomey, MD, a cardiologist with the Mount Sinai Health System, New York, who was not involved with the study. An interventional trial would be needed to confirm the findings.
The finding that sleep was better for participants than sitting is a good example. The benefits of replacing sitting with sleep were “clear” for adiposity measures like BMI and waist circumference, but negligible for blood markers such as cholesterol, triglycerides, and blood glucose, Dr. Blodgett said.
One explanation: “The negative impact of sitting on these obesity measures is likely due to related unhealthy behaviors like snacking rather than the physiological benefits of sleep itself,” Dr. Blodgett said.
What’s more, study participants were relatively young, healthy, and active. The average age was 54, and they averaged nearly 8 hours of sleep, 10 hours of sitting, 3 hours of standing, 1.5 hours of light activity, and more than an hour of moderate to vigorous activity per day. So it’s difficult to draw conclusions about patients who don’t fit those metrics.
Impact on patient care
That said, the results could help tailor recommendations for patients, Dr. Blodgett said.
If a patient is struggling to exercise or is unable to exercise because of health or ability restrictions, you could help them find ways to add a lighter activity to their day, such as taking the stairs or walking briskly to catch the bus. Even swapping a regular desk for a standing one, or going to bed 30 minutes earlier, could be a more practical and effective suggestion.
More than that: The research could be used to educate patients on the power of small changes. It shows that shifting daily habits even in small ways can make a difference, and people who are the least active stand to benefit the most.
You can also remind patients that moderate or vigorous activity doesn’t need to happen at the gym. It could be lawn work, taking a walk, or moving heavy boxes. In fact, many activities can be “moderate” or even “vigorous” depending on the effort put into them.
Share this rule of thumb: “An activity is classified as moderate intensity if you can talk but not sing while doing it, and an activity is generally considered vigorous intensity if you can’t say more than a few words without stopping to breathe,” Dr. Blodgett said.
The study also has implications for the potential of wearable activity trackers to monitor progress. Combining objective activity data with results from studies like this, and longer prospective studies, could help inform more helpful advice.
“Ultimately, this research helps move us closer to more personalized guidance of how changing behaviors can improve your health,” Dr. Blodgett said.
A version of this article first appeared on Medscape.com.
Sit less, move more. Or stand more. Or sleep more.
Replacing 30 minutes of sitting a day with equal time standing or even sleeping could improve obesity markers like body weight and waist circumference, according to a new cross-sectional study investigating the impact of movement behavior on cardiometabolic health.
The findings suggest that, while higher-intensity activity may confer benefits sooner, adding more light activity or more standing, or even going to bed earlier, could improve heart health measures over time.
“Our study highlights that replacing sedentary behavior with any other behavior can be beneficial,” said study author Joanna M. Blodgett, PhD, a researcher at University College London’s Institute of Sport, Exercise and Health, and department of targeted intervention.
The study builds on a large and growing body of evidence that movement behaviors impact cardiometabolic health. Increasing physical activity to 150 minutes a week has been shown to reduce the risk for cardiovascular disease by 17% and type 2 diabetes by 26%. Other studies suggest that even modest increases in physical activity can be beneficial. A prospective study published in October found that even short activity bouts of a few minutes a day may lower risks for heart attack, stroke, and early death.
In the new study, researchers analyzed data from six studies and more than 15,000 participants, ranking behaviors according to their association with heart health. Moderate-to-vigorous activity was linked to the greatest benefit, followed by light activity, standing, sleeping, and finally – dead last on the list – sitting.
A thigh-worn device tracked participants’ activity throughout the day, and six measures gauged heart health: body mass index (BMI), waist circumference, HDL cholesterol, total-cholesterol-to-HDL ratio, triglycerides, and glycated hemoglobin.
Researchers modeled what would happen if people swapped various amounts of one activity for another every day for a week. Replacing just 4-13 minutes of sitting with moderate to vigorous activity improved heart health markers.
The cardiovascular demands of regular intense activity like running, cycling, dancing, or playing sports – even in small bouts – strengthen the heart and improve blood flow throughout the body, Dr. Blodgett said. “This can lower cholesterol, blood pressure, and resting heart rate.”
Even if adding moderate to vigorous activity is not an option, the findings suggest that people can still see benefits by replacing sitting with virtually any other activity – walking, standing, even sleeping.
Limitations
Because the study was observational, results can’t be used to infer causality.
“We cannot directly lean on the study results to guide prescriptions for particular exercise or lifestyle changes,” said Matthew Tomey, MD, a cardiologist with the Mount Sinai Health System, New York, who was not involved with the study. An interventional trial would be needed to confirm the findings.
The finding that sleep was better for participants than sitting is a good example. The benefits of replacing sitting with sleep were “clear” for adiposity measures like BMI and waist circumference, but negligible for blood markers such as cholesterol, triglycerides, and blood glucose, Dr. Blodgett said.
One explanation: “The negative impact of sitting on these obesity measures is likely due to related unhealthy behaviors like snacking rather than the physiological benefits of sleep itself,” Dr. Blodgett said.
What’s more, study participants were relatively young, healthy, and active. The average age was 54, and they averaged nearly 8 hours of sleep, 10 hours of sitting, 3 hours of standing, 1.5 hours of light activity, and more than an hour of moderate to vigorous activity per day. So it’s difficult to draw conclusions about patients who don’t fit those metrics.
Impact on patient care
That said, the results could help tailor recommendations for patients, Dr. Blodgett said.
If a patient is struggling to exercise or is unable to exercise because of health or ability restrictions, you could help them find ways to add a lighter activity to their day, such as taking the stairs or walking briskly to catch the bus. Even swapping a regular desk for a standing one, or going to bed 30 minutes earlier, could be a more practical and effective suggestion.
More than that: The research could be used to educate patients on the power of small changes. It shows that shifting daily habits even in small ways can make a difference, and people who are the least active stand to benefit the most.
You can also remind patients that moderate or vigorous activity doesn’t need to happen at the gym. It could be lawn work, taking a walk, or moving heavy boxes. In fact, many activities can be “moderate” or even “vigorous” depending on the effort put into them.
Share this rule of thumb: “An activity is classified as moderate intensity if you can talk but not sing while doing it, and an activity is generally considered vigorous intensity if you can’t say more than a few words without stopping to breathe,” Dr. Blodgett said.
The study also has implications for the potential of wearable activity trackers to monitor progress. Combining objective activity data with results from studies like this, and longer prospective studies, could help inform more helpful advice.
“Ultimately, this research helps move us closer to more personalized guidance of how changing behaviors can improve your health,” Dr. Blodgett said.
A version of this article first appeared on Medscape.com.
Sit less, move more. Or stand more. Or sleep more.
Replacing 30 minutes of sitting a day with equal time standing or even sleeping could improve obesity markers like body weight and waist circumference, according to a new cross-sectional study investigating the impact of movement behavior on cardiometabolic health.
The findings suggest that, while higher-intensity activity may confer benefits sooner, adding more light activity or more standing, or even going to bed earlier, could improve heart health measures over time.
“Our study highlights that replacing sedentary behavior with any other behavior can be beneficial,” said study author Joanna M. Blodgett, PhD, a researcher at University College London’s Institute of Sport, Exercise and Health, and department of targeted intervention.
The study builds on a large and growing body of evidence that movement behaviors impact cardiometabolic health. Increasing physical activity to 150 minutes a week has been shown to reduce the risk for cardiovascular disease by 17% and type 2 diabetes by 26%. Other studies suggest that even modest increases in physical activity can be beneficial. A prospective study published in October found that even short activity bouts of a few minutes a day may lower risks for heart attack, stroke, and early death.
In the new study, researchers analyzed data from six studies and more than 15,000 participants, ranking behaviors according to their association with heart health. Moderate-to-vigorous activity was linked to the greatest benefit, followed by light activity, standing, sleeping, and finally – dead last on the list – sitting.
A thigh-worn device tracked participants’ activity throughout the day, and six measures gauged heart health: body mass index (BMI), waist circumference, HDL cholesterol, total-cholesterol-to-HDL ratio, triglycerides, and glycated hemoglobin.
Researchers modeled what would happen if people swapped various amounts of one activity for another every day for a week. Replacing just 4-13 minutes of sitting with moderate to vigorous activity improved heart health markers.
The cardiovascular demands of regular intense activity like running, cycling, dancing, or playing sports – even in small bouts – strengthen the heart and improve blood flow throughout the body, Dr. Blodgett said. “This can lower cholesterol, blood pressure, and resting heart rate.”
Even if adding moderate to vigorous activity is not an option, the findings suggest that people can still see benefits by replacing sitting with virtually any other activity – walking, standing, even sleeping.
Limitations
Because the study was observational, results can’t be used to infer causality.
“We cannot directly lean on the study results to guide prescriptions for particular exercise or lifestyle changes,” said Matthew Tomey, MD, a cardiologist with the Mount Sinai Health System, New York, who was not involved with the study. An interventional trial would be needed to confirm the findings.
The finding that sleep was better for participants than sitting is a good example. The benefits of replacing sitting with sleep were “clear” for adiposity measures like BMI and waist circumference, but negligible for blood markers such as cholesterol, triglycerides, and blood glucose, Dr. Blodgett said.
One explanation: “The negative impact of sitting on these obesity measures is likely due to related unhealthy behaviors like snacking rather than the physiological benefits of sleep itself,” Dr. Blodgett said.
What’s more, study participants were relatively young, healthy, and active. The average age was 54, and they averaged nearly 8 hours of sleep, 10 hours of sitting, 3 hours of standing, 1.5 hours of light activity, and more than an hour of moderate to vigorous activity per day. So it’s difficult to draw conclusions about patients who don’t fit those metrics.
Impact on patient care
That said, the results could help tailor recommendations for patients, Dr. Blodgett said.
If a patient is struggling to exercise or is unable to exercise because of health or ability restrictions, you could help them find ways to add a lighter activity to their day, such as taking the stairs or walking briskly to catch the bus. Even swapping a regular desk for a standing one, or going to bed 30 minutes earlier, could be a more practical and effective suggestion.
More than that: The research could be used to educate patients on the power of small changes. It shows that shifting daily habits even in small ways can make a difference, and people who are the least active stand to benefit the most.
You can also remind patients that moderate or vigorous activity doesn’t need to happen at the gym. It could be lawn work, taking a walk, or moving heavy boxes. In fact, many activities can be “moderate” or even “vigorous” depending on the effort put into them.
Share this rule of thumb: “An activity is classified as moderate intensity if you can talk but not sing while doing it, and an activity is generally considered vigorous intensity if you can’t say more than a few words without stopping to breathe,” Dr. Blodgett said.
The study also has implications for the potential of wearable activity trackers to monitor progress. Combining objective activity data with results from studies like this, and longer prospective studies, could help inform more helpful advice.
“Ultimately, this research helps move us closer to more personalized guidance of how changing behaviors can improve your health,” Dr. Blodgett said.
A version of this article first appeared on Medscape.com.
FROM THE EUROPEAN HEART JOURNAL
Does laughter offer better blood glucose control?
David S. Greene, PhD, associate professor in the department of rehabilitation and human services at the University of Northern Colorado, Greeley, has pioneered research into the field, one previously overlooked when it comes to diabetes management.
This news organization caught up with Dr. Greene to ask about his research along with the implications for diabetes care and for patient well-being.
Question: What prompted you to research the link between humor and diabetes control?
Answer: I was diagnosed with type 1 diabetes in 1966 and consequently have lived with, and studied, various aspects of diabetes for the past 57 years.
For a time, I maintained a small private practice counseling people with diabetes. There I noticed, anecdotally, that my clients’ ability to laugh at, and see the humor in, their diabetes correlated with their emotional adjustment to living with their condition.
While I could find research confirming the physical and psychological benefits of humor in general, I was unable to find any research specifically relating to humor and diabetes.
My new research agenda was born.
Q: What did your research reveal?
A: My first study, published in 2020, found that people living with diabetes displayed the same level of both types of positive, or affiliative and self-enhancing, humor as the norm group used in developing the Humor Styles Questionnaire.
This was a surprising finding given that individuals with diabetes are dealing with a life-altering, chronic illness, with higher rates of depression and anxiety. Moreover, positive humor scores are known to be negatively correlated with depression and anxiety.
While levels of aggressive humor were not altered in my study, people with diabetes did have higher levels of self-defeating humor in my study, which is correlated with psychiatric and somatic concerns, and symptomatology, and so is to be expected.
My second study, published in 2021, examined whether there was a difference between people with diabetes who had an hemoglobin A1c level of 6.99% or less versus those with levels of at least 7% on four disparate types of humor.
The A1c of 6.99% or less group scored significantly higher for both affiliative humor and self-enhancing humor. This implies that better diabetes control is associated with positive humor. This was expected, as was the finding that negative humor was not associated with better control.
On the other hand, there was no significant difference between participants on either type of negative humor, whether aggressive or self-defeating.
Finally, my third study, published in 2023 [with coauthor Nancy D. King, PhD], found that offering humor training to people with type 1 diabetes can strengthen both their affiliative and self-enhancing sense of humor, while leaving their aggressive or self-defeating humor unaffected.
Q: What is ‘positive humor,’ and why do you think it is associated with diabetes control?
A: Both affiliative and self-enhancing humor enhance a person’s sense of self and their relationships with others.
Affiliative humor has been shown to be positively correlated with self-esteem, psychological well-being, social intimacy, and emotional stability. It is also negatively correlated with depression and anxiety.
Self-enhancing humor involves the ability to maintain a humorous outlook on life and to use humor to regulate emotions and as a coping strategy. Like affiliative humor, it is correlated with cheerfulness, self-esteem, optimism, psychological well-being, and life satisfaction. It is negatively related to depression and anxiety.
The preponderance of literature suggests positive humor specifically is associated with buffering many of the risk factors and complications associated with diabetes.
Q: What could underlie the associations between humor and diabetes control?
A: Unfortunately, none of my studies have been able to determine cause and effect, although the most recent one came the closest.
While not reaching statistical significance, the mean reduction in A1c levels from 7.12% at baseline to 6.75% at the post–humor training assessment may very well imply a practical and psychological significance to patients.
I believe, with a larger sample size, significance will be achieved, and that the relationship between positive humor and diabetes control will be shown to be bidirectional, with positive humor improving diabetes control, and improved control improving positive humor.
I hypothesize this will also bring psychological and physiological benefits. After all, humor has already been associated with reduced blood glucose levels, reduced microvascular complications, improved heart health, reduced blood pressure, decreased levels of depression and anxiety.
Humor also helps us deal with stress and trauma, so a cause-and-effect relationship makes sense.
Q: Can a positive sense of humor be taught?
A: Absolutely. There is evidence that humor can be developed and strengthened. Paul McGhee, PhD, developed a seven-step humor training program that has been effective in elevating measures of humor across a number of studies.
Others have successfully developed their own protocols, and of course my third study demonstrated a significant increase in both affiliative and self-enhancing humor with training.
Q: Do you think humor training could be incorporated into diabetes care?
A: Humor training programs are easily accessible, incur low to no cost, and are easy to implement. Furthermore, once a person is trained, access to ongoing humor is free, readily available, and fun.
Several diabetes educators have also reported that humor can promote connections, encourage and support diabetes management, galvanize effectiveness, and increase an audience’s attention during education programs.
A version of this article appeared on Medscape.com.
David S. Greene, PhD, associate professor in the department of rehabilitation and human services at the University of Northern Colorado, Greeley, has pioneered research into the field, one previously overlooked when it comes to diabetes management.
This news organization caught up with Dr. Greene to ask about his research along with the implications for diabetes care and for patient well-being.
Question: What prompted you to research the link between humor and diabetes control?
Answer: I was diagnosed with type 1 diabetes in 1966 and consequently have lived with, and studied, various aspects of diabetes for the past 57 years.
For a time, I maintained a small private practice counseling people with diabetes. There I noticed, anecdotally, that my clients’ ability to laugh at, and see the humor in, their diabetes correlated with their emotional adjustment to living with their condition.
While I could find research confirming the physical and psychological benefits of humor in general, I was unable to find any research specifically relating to humor and diabetes.
My new research agenda was born.
Q: What did your research reveal?
A: My first study, published in 2020, found that people living with diabetes displayed the same level of both types of positive, or affiliative and self-enhancing, humor as the norm group used in developing the Humor Styles Questionnaire.
This was a surprising finding given that individuals with diabetes are dealing with a life-altering, chronic illness, with higher rates of depression and anxiety. Moreover, positive humor scores are known to be negatively correlated with depression and anxiety.
While levels of aggressive humor were not altered in my study, people with diabetes did have higher levels of self-defeating humor in my study, which is correlated with psychiatric and somatic concerns, and symptomatology, and so is to be expected.
My second study, published in 2021, examined whether there was a difference between people with diabetes who had an hemoglobin A1c level of 6.99% or less versus those with levels of at least 7% on four disparate types of humor.
The A1c of 6.99% or less group scored significantly higher for both affiliative humor and self-enhancing humor. This implies that better diabetes control is associated with positive humor. This was expected, as was the finding that negative humor was not associated with better control.
On the other hand, there was no significant difference between participants on either type of negative humor, whether aggressive or self-defeating.
Finally, my third study, published in 2023 [with coauthor Nancy D. King, PhD], found that offering humor training to people with type 1 diabetes can strengthen both their affiliative and self-enhancing sense of humor, while leaving their aggressive or self-defeating humor unaffected.
Q: What is ‘positive humor,’ and why do you think it is associated with diabetes control?
A: Both affiliative and self-enhancing humor enhance a person’s sense of self and their relationships with others.
Affiliative humor has been shown to be positively correlated with self-esteem, psychological well-being, social intimacy, and emotional stability. It is also negatively correlated with depression and anxiety.
Self-enhancing humor involves the ability to maintain a humorous outlook on life and to use humor to regulate emotions and as a coping strategy. Like affiliative humor, it is correlated with cheerfulness, self-esteem, optimism, psychological well-being, and life satisfaction. It is negatively related to depression and anxiety.
The preponderance of literature suggests positive humor specifically is associated with buffering many of the risk factors and complications associated with diabetes.
Q: What could underlie the associations between humor and diabetes control?
A: Unfortunately, none of my studies have been able to determine cause and effect, although the most recent one came the closest.
While not reaching statistical significance, the mean reduction in A1c levels from 7.12% at baseline to 6.75% at the post–humor training assessment may very well imply a practical and psychological significance to patients.
I believe, with a larger sample size, significance will be achieved, and that the relationship between positive humor and diabetes control will be shown to be bidirectional, with positive humor improving diabetes control, and improved control improving positive humor.
I hypothesize this will also bring psychological and physiological benefits. After all, humor has already been associated with reduced blood glucose levels, reduced microvascular complications, improved heart health, reduced blood pressure, decreased levels of depression and anxiety.
Humor also helps us deal with stress and trauma, so a cause-and-effect relationship makes sense.
Q: Can a positive sense of humor be taught?
A: Absolutely. There is evidence that humor can be developed and strengthened. Paul McGhee, PhD, developed a seven-step humor training program that has been effective in elevating measures of humor across a number of studies.
Others have successfully developed their own protocols, and of course my third study demonstrated a significant increase in both affiliative and self-enhancing humor with training.
Q: Do you think humor training could be incorporated into diabetes care?
A: Humor training programs are easily accessible, incur low to no cost, and are easy to implement. Furthermore, once a person is trained, access to ongoing humor is free, readily available, and fun.
Several diabetes educators have also reported that humor can promote connections, encourage and support diabetes management, galvanize effectiveness, and increase an audience’s attention during education programs.
A version of this article appeared on Medscape.com.
David S. Greene, PhD, associate professor in the department of rehabilitation and human services at the University of Northern Colorado, Greeley, has pioneered research into the field, one previously overlooked when it comes to diabetes management.
This news organization caught up with Dr. Greene to ask about his research along with the implications for diabetes care and for patient well-being.
Question: What prompted you to research the link between humor and diabetes control?
Answer: I was diagnosed with type 1 diabetes in 1966 and consequently have lived with, and studied, various aspects of diabetes for the past 57 years.
For a time, I maintained a small private practice counseling people with diabetes. There I noticed, anecdotally, that my clients’ ability to laugh at, and see the humor in, their diabetes correlated with their emotional adjustment to living with their condition.
While I could find research confirming the physical and psychological benefits of humor in general, I was unable to find any research specifically relating to humor and diabetes.
My new research agenda was born.
Q: What did your research reveal?
A: My first study, published in 2020, found that people living with diabetes displayed the same level of both types of positive, or affiliative and self-enhancing, humor as the norm group used in developing the Humor Styles Questionnaire.
This was a surprising finding given that individuals with diabetes are dealing with a life-altering, chronic illness, with higher rates of depression and anxiety. Moreover, positive humor scores are known to be negatively correlated with depression and anxiety.
While levels of aggressive humor were not altered in my study, people with diabetes did have higher levels of self-defeating humor in my study, which is correlated with psychiatric and somatic concerns, and symptomatology, and so is to be expected.
My second study, published in 2021, examined whether there was a difference between people with diabetes who had an hemoglobin A1c level of 6.99% or less versus those with levels of at least 7% on four disparate types of humor.
The A1c of 6.99% or less group scored significantly higher for both affiliative humor and self-enhancing humor. This implies that better diabetes control is associated with positive humor. This was expected, as was the finding that negative humor was not associated with better control.
On the other hand, there was no significant difference between participants on either type of negative humor, whether aggressive or self-defeating.
Finally, my third study, published in 2023 [with coauthor Nancy D. King, PhD], found that offering humor training to people with type 1 diabetes can strengthen both their affiliative and self-enhancing sense of humor, while leaving their aggressive or self-defeating humor unaffected.
Q: What is ‘positive humor,’ and why do you think it is associated with diabetes control?
A: Both affiliative and self-enhancing humor enhance a person’s sense of self and their relationships with others.
Affiliative humor has been shown to be positively correlated with self-esteem, psychological well-being, social intimacy, and emotional stability. It is also negatively correlated with depression and anxiety.
Self-enhancing humor involves the ability to maintain a humorous outlook on life and to use humor to regulate emotions and as a coping strategy. Like affiliative humor, it is correlated with cheerfulness, self-esteem, optimism, psychological well-being, and life satisfaction. It is negatively related to depression and anxiety.
The preponderance of literature suggests positive humor specifically is associated with buffering many of the risk factors and complications associated with diabetes.
Q: What could underlie the associations between humor and diabetes control?
A: Unfortunately, none of my studies have been able to determine cause and effect, although the most recent one came the closest.
While not reaching statistical significance, the mean reduction in A1c levels from 7.12% at baseline to 6.75% at the post–humor training assessment may very well imply a practical and psychological significance to patients.
I believe, with a larger sample size, significance will be achieved, and that the relationship between positive humor and diabetes control will be shown to be bidirectional, with positive humor improving diabetes control, and improved control improving positive humor.
I hypothesize this will also bring psychological and physiological benefits. After all, humor has already been associated with reduced blood glucose levels, reduced microvascular complications, improved heart health, reduced blood pressure, decreased levels of depression and anxiety.
Humor also helps us deal with stress and trauma, so a cause-and-effect relationship makes sense.
Q: Can a positive sense of humor be taught?
A: Absolutely. There is evidence that humor can be developed and strengthened. Paul McGhee, PhD, developed a seven-step humor training program that has been effective in elevating measures of humor across a number of studies.
Others have successfully developed their own protocols, and of course my third study demonstrated a significant increase in both affiliative and self-enhancing humor with training.
Q: Do you think humor training could be incorporated into diabetes care?
A: Humor training programs are easily accessible, incur low to no cost, and are easy to implement. Furthermore, once a person is trained, access to ongoing humor is free, readily available, and fun.
Several diabetes educators have also reported that humor can promote connections, encourage and support diabetes management, galvanize effectiveness, and increase an audience’s attention during education programs.
A version of this article appeared on Medscape.com.
Low-salt diet cut BP by 6 mm Hg in 1 week: CARDIA-SSBP
The CARDIA-SSBP trial involved 213 individuals aged 50-75 years, including those with and those without hypertension, and showed that the decline in blood pressure brought about by a low-salt diet was independent of hypertension status and antihypertensive medication use. It was also generally consistent across subgroups and did not result in excess adverse events.
“The blood pressure reduction we see here is meaningful, and comparable to that produced by one antihypertensive medication,” lead investigator Deepak Gupta, MD, Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.
Dr. Gupta presented the CARDIA-SSBP study on Nov. 11 at the American Heart Association scientific sessions, held in Philadelphia. The study was published online in JAMA. The exact menus used in the study are available in a supplement to the JAMA paper.
“In order to live a healthy lifestyle, understanding what we eat has important health effects. Raised blood pressure contributes to one out of every eight deaths worldwide,” Dr. Gupta noted. “If people want to lower their blood pressure, attention to dietary sodium is one part of that. If individuals can stick with a low sodium diet, they may be able to stop taking one of their antihypertensive medications, and those who are normotensive will be less likely to develop hypertension.”
Commentators said the study had significant implications for public health, but they pointed out that maintaining a low-sodium diet over the long term is challenging, given the high salt content of generally available foods.
Dr. Gupta noted that the study did use commercially available products in the low-sodium diets and the menus are available for people to follow, making it more accessible than some diets used in previous studies.
“What may also be attractive to people is that you don’t have to wait for months to see an effect. If you start to consume a low-sodium diet, you can see results on blood pressure rapidly, within a week,” he said.
The diet in this study brought about a large reduction in dietary sodium, but Dr. Gupta says any reduction in dietary sodium is likely to be beneficial.
“If you go to the level that we got to, you could expect to see a reduction of around 6 mm Hg. But it’s like walking – you don’t necessarily need to get to 10,000 steps every day. Any amount of walking or physical activity is of benefit. The same is probably true for salt: Any reduction that you can make is probably of benefit.”
For the study, participants had their blood pressure measured by 24-hour ambulatory monitoring while on their usual diets. They were then randomly assigned to either a high-sodium diet or a low-sodium diet for 1 week. Participants then crossed over to the opposite diet for 1 week, with blood pressure measured over a 24-hour period on the last day of each diet.
As assessed by 24-hour urine excretion, the usual diet of participants was found to already be high in sodium (median, 4.45 g/d). This increased to a median of 5.00 g/d when on the high-sodium diet in the study and decreased to 1.27 g/d while on the low-sodium diet.
Results found participants had a median systolic blood pressure of 125 mm Hg on their usual diets. This was raised to 126 mm Hg on the high-sodium diet and lowered to 119 mm Hg on the low-sodium diet.
The researchers also reported that 75% of individuals showed a blood pressure reduction on the low-sodium diet and are thus defined as “salt-sensitive.” This is a higher percentage than found in previous studies.
“Of those that didn’t show a blood pressure reduction with a low-sodium diet in this study, it appears that they may not have been so adherent to the diet as those who did show a blood pressure reduction,” Dr. Gupta said.
He noted that hypertension is the most common chronic disease condition worldwide, with about 1.3 billion people affected, and although it has been known for some time that dietary sodium affects blood pressure, there have been some gaps in previous studies.
For example, many studies have excluded individuals who were already taking antihypertensive medications and people with diabetes, and they have generally not included many older individuals. The current study found that all of these groups showed significant blood pressure reductions by reducing dietary sodium.
Large effect in people with diabetes
Subgroup analysis largely showed consistent results across the population, regardless of age, sex, race, and body mass index and whether participants were taking antihypertensive medication or not, but there were a couple of exceptions. Individuals with higher blood pressure at baseline seemed to have a greater effect of lowering dietary sodium, although those who were normotensive at baseline still showed significant blood pressure reduction, Dr. Gupta reported.
The researchers found a particularly large reduction in blood pressure from lowering sodium intake in people with diabetes, who made up about 21% of the overall cohort. Their average reduction in systolic blood pressure between the high and low sodium diet was close to 17 mm Hg rather than the 7-8 mm Hg in the whole cohort.
Dr. Gupta said that the results are applicable to most of the population.
“The people who will be most motivated to follow a low-sodium diet are those with hypertension. But even in normotensive individuals, there is likely to be benefit.”
To help people follow a low-sodium diet, Dr. Gupta says education campaigns are needed “to show people that they can do it and make it work.” But there are bigger structural issues that need to be addressed at policy and governmental levels.
“Most of our food available in grocery stores and restaurants is high in salt. We now have a preponderance of evidence showing us that we need to change what’s available in the food supply,” he said. “There is a push going on for this now, and the U.S. has introduced some guidelines for the food industry on sodium content of foods. These are voluntary at this point, but it’s a start.”
Difficult to maintain long term
Commenting on the study, Paul Whelton, MD, chair in global public health at Tulane University, New Orleans, noted that sodium reduction is known to reduce blood pressure, with greater sodium reductions giving greater blood pressure decreases, and that some people are more sensitive to the effects of sodium than others.
He described CARDIA-SSBP as a “well-done study.”
“They managed to get a very low sodium intake and a large difference between the two groups, which translated into a big reduction in systolic blood pressure,” Dr. Whelton said. “However, the problem with these sorts of trials where the diets are provided to the participants is that although they show proof of concept, it is difficult to generalize because we can’t normally provide patients with their meals. In this type of ‘feeding’ study, we find it difficult to maintain people on their behavioral intervention over the long term.”
Dr. Whelton said that he was more excited about this trial knowing that the food given was commercially available. “That makes it more practical, but you still have to be quite motivated to follow a diet like this. Buying low-sodium products in the supermarket does require quite a lot of work to read the labels, and sometimes the low-sodium foods are specialty products and are more expensive.”
He pointed out that older people in higher socioeconomic classes are more likely to attempt this and do better from behavioral interventions in general. “Unfortunately, people who don’t do well from behavioral interventions like this are those from lower socioeconomic groups, who are ones at most at risk for cardiovascular disease.”
Dr. Whelton noted that the food industry has been reluctant to lower sodium content because high-salt foods sell better. “Unfortunately, foods high in saturated fat and salt taste good to most people. We are generally attuned to a high salt intake. But when people have been following a low-salt diet for a while, they generally don’t like high-salt foods anymore. They become attuned to lower-sodium diet,” he added.
New U.S. sodium reduction guidelines
Discussant of the CARDIA-SSBP study at the AHA meeting, Cheryl Anderson, MD, University of California, San Diego, said that the findings were important and consistent with prior studies.
“These studies have global implications because salt is ubiquitous in the food supply in much of the world,” she noted, adding that, “Americans consume almost 50% more sodium than recommended, and there has been a persistent lack of adherence to healthy diet recommendations for reductions in salt, sugar, and fats.”
Dr. Anderson pointed out that in 2021, the Food and Drug Administration issued guidance for voluntary sodium reduction, which uses a gradual approach, with targets to reach a population goal of 3,000 mg/d of sodium by 2023 and 2,300 mg/d by 2031.
“These targets apply to 150 categories of food that are sales-weighted to focus on dominant sellers in each category. They apply to food manufacturers, restaurants and food service operations,” she concluded. “These targets serve as a basis for continued dialogue. The research community eagerly awaits the review of population-based data to help refine this approach and goals.”
This study was supported by grants from the National Heart, Lung, and Blood Institute, the National Institutes of Health, the American Heart Association, and the National Center for Advancing Translational Sciences. The authors report no disclosures.
A version of this article appeared on Medscape.com.
The CARDIA-SSBP trial involved 213 individuals aged 50-75 years, including those with and those without hypertension, and showed that the decline in blood pressure brought about by a low-salt diet was independent of hypertension status and antihypertensive medication use. It was also generally consistent across subgroups and did not result in excess adverse events.
“The blood pressure reduction we see here is meaningful, and comparable to that produced by one antihypertensive medication,” lead investigator Deepak Gupta, MD, Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.
Dr. Gupta presented the CARDIA-SSBP study on Nov. 11 at the American Heart Association scientific sessions, held in Philadelphia. The study was published online in JAMA. The exact menus used in the study are available in a supplement to the JAMA paper.
“In order to live a healthy lifestyle, understanding what we eat has important health effects. Raised blood pressure contributes to one out of every eight deaths worldwide,” Dr. Gupta noted. “If people want to lower their blood pressure, attention to dietary sodium is one part of that. If individuals can stick with a low sodium diet, they may be able to stop taking one of their antihypertensive medications, and those who are normotensive will be less likely to develop hypertension.”
Commentators said the study had significant implications for public health, but they pointed out that maintaining a low-sodium diet over the long term is challenging, given the high salt content of generally available foods.
Dr. Gupta noted that the study did use commercially available products in the low-sodium diets and the menus are available for people to follow, making it more accessible than some diets used in previous studies.
“What may also be attractive to people is that you don’t have to wait for months to see an effect. If you start to consume a low-sodium diet, you can see results on blood pressure rapidly, within a week,” he said.
The diet in this study brought about a large reduction in dietary sodium, but Dr. Gupta says any reduction in dietary sodium is likely to be beneficial.
“If you go to the level that we got to, you could expect to see a reduction of around 6 mm Hg. But it’s like walking – you don’t necessarily need to get to 10,000 steps every day. Any amount of walking or physical activity is of benefit. The same is probably true for salt: Any reduction that you can make is probably of benefit.”
For the study, participants had their blood pressure measured by 24-hour ambulatory monitoring while on their usual diets. They were then randomly assigned to either a high-sodium diet or a low-sodium diet for 1 week. Participants then crossed over to the opposite diet for 1 week, with blood pressure measured over a 24-hour period on the last day of each diet.
As assessed by 24-hour urine excretion, the usual diet of participants was found to already be high in sodium (median, 4.45 g/d). This increased to a median of 5.00 g/d when on the high-sodium diet in the study and decreased to 1.27 g/d while on the low-sodium diet.
Results found participants had a median systolic blood pressure of 125 mm Hg on their usual diets. This was raised to 126 mm Hg on the high-sodium diet and lowered to 119 mm Hg on the low-sodium diet.
The researchers also reported that 75% of individuals showed a blood pressure reduction on the low-sodium diet and are thus defined as “salt-sensitive.” This is a higher percentage than found in previous studies.
“Of those that didn’t show a blood pressure reduction with a low-sodium diet in this study, it appears that they may not have been so adherent to the diet as those who did show a blood pressure reduction,” Dr. Gupta said.
He noted that hypertension is the most common chronic disease condition worldwide, with about 1.3 billion people affected, and although it has been known for some time that dietary sodium affects blood pressure, there have been some gaps in previous studies.
For example, many studies have excluded individuals who were already taking antihypertensive medications and people with diabetes, and they have generally not included many older individuals. The current study found that all of these groups showed significant blood pressure reductions by reducing dietary sodium.
Large effect in people with diabetes
Subgroup analysis largely showed consistent results across the population, regardless of age, sex, race, and body mass index and whether participants were taking antihypertensive medication or not, but there were a couple of exceptions. Individuals with higher blood pressure at baseline seemed to have a greater effect of lowering dietary sodium, although those who were normotensive at baseline still showed significant blood pressure reduction, Dr. Gupta reported.
The researchers found a particularly large reduction in blood pressure from lowering sodium intake in people with diabetes, who made up about 21% of the overall cohort. Their average reduction in systolic blood pressure between the high and low sodium diet was close to 17 mm Hg rather than the 7-8 mm Hg in the whole cohort.
Dr. Gupta said that the results are applicable to most of the population.
“The people who will be most motivated to follow a low-sodium diet are those with hypertension. But even in normotensive individuals, there is likely to be benefit.”
To help people follow a low-sodium diet, Dr. Gupta says education campaigns are needed “to show people that they can do it and make it work.” But there are bigger structural issues that need to be addressed at policy and governmental levels.
“Most of our food available in grocery stores and restaurants is high in salt. We now have a preponderance of evidence showing us that we need to change what’s available in the food supply,” he said. “There is a push going on for this now, and the U.S. has introduced some guidelines for the food industry on sodium content of foods. These are voluntary at this point, but it’s a start.”
Difficult to maintain long term
Commenting on the study, Paul Whelton, MD, chair in global public health at Tulane University, New Orleans, noted that sodium reduction is known to reduce blood pressure, with greater sodium reductions giving greater blood pressure decreases, and that some people are more sensitive to the effects of sodium than others.
He described CARDIA-SSBP as a “well-done study.”
“They managed to get a very low sodium intake and a large difference between the two groups, which translated into a big reduction in systolic blood pressure,” Dr. Whelton said. “However, the problem with these sorts of trials where the diets are provided to the participants is that although they show proof of concept, it is difficult to generalize because we can’t normally provide patients with their meals. In this type of ‘feeding’ study, we find it difficult to maintain people on their behavioral intervention over the long term.”
Dr. Whelton said that he was more excited about this trial knowing that the food given was commercially available. “That makes it more practical, but you still have to be quite motivated to follow a diet like this. Buying low-sodium products in the supermarket does require quite a lot of work to read the labels, and sometimes the low-sodium foods are specialty products and are more expensive.”
He pointed out that older people in higher socioeconomic classes are more likely to attempt this and do better from behavioral interventions in general. “Unfortunately, people who don’t do well from behavioral interventions like this are those from lower socioeconomic groups, who are ones at most at risk for cardiovascular disease.”
Dr. Whelton noted that the food industry has been reluctant to lower sodium content because high-salt foods sell better. “Unfortunately, foods high in saturated fat and salt taste good to most people. We are generally attuned to a high salt intake. But when people have been following a low-salt diet for a while, they generally don’t like high-salt foods anymore. They become attuned to lower-sodium diet,” he added.
New U.S. sodium reduction guidelines
Discussant of the CARDIA-SSBP study at the AHA meeting, Cheryl Anderson, MD, University of California, San Diego, said that the findings were important and consistent with prior studies.
“These studies have global implications because salt is ubiquitous in the food supply in much of the world,” she noted, adding that, “Americans consume almost 50% more sodium than recommended, and there has been a persistent lack of adherence to healthy diet recommendations for reductions in salt, sugar, and fats.”
Dr. Anderson pointed out that in 2021, the Food and Drug Administration issued guidance for voluntary sodium reduction, which uses a gradual approach, with targets to reach a population goal of 3,000 mg/d of sodium by 2023 and 2,300 mg/d by 2031.
“These targets apply to 150 categories of food that are sales-weighted to focus on dominant sellers in each category. They apply to food manufacturers, restaurants and food service operations,” she concluded. “These targets serve as a basis for continued dialogue. The research community eagerly awaits the review of population-based data to help refine this approach and goals.”
This study was supported by grants from the National Heart, Lung, and Blood Institute, the National Institutes of Health, the American Heart Association, and the National Center for Advancing Translational Sciences. The authors report no disclosures.
A version of this article appeared on Medscape.com.
The CARDIA-SSBP trial involved 213 individuals aged 50-75 years, including those with and those without hypertension, and showed that the decline in blood pressure brought about by a low-salt diet was independent of hypertension status and antihypertensive medication use. It was also generally consistent across subgroups and did not result in excess adverse events.
“The blood pressure reduction we see here is meaningful, and comparable to that produced by one antihypertensive medication,” lead investigator Deepak Gupta, MD, Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.
Dr. Gupta presented the CARDIA-SSBP study on Nov. 11 at the American Heart Association scientific sessions, held in Philadelphia. The study was published online in JAMA. The exact menus used in the study are available in a supplement to the JAMA paper.
“In order to live a healthy lifestyle, understanding what we eat has important health effects. Raised blood pressure contributes to one out of every eight deaths worldwide,” Dr. Gupta noted. “If people want to lower their blood pressure, attention to dietary sodium is one part of that. If individuals can stick with a low sodium diet, they may be able to stop taking one of their antihypertensive medications, and those who are normotensive will be less likely to develop hypertension.”
Commentators said the study had significant implications for public health, but they pointed out that maintaining a low-sodium diet over the long term is challenging, given the high salt content of generally available foods.
Dr. Gupta noted that the study did use commercially available products in the low-sodium diets and the menus are available for people to follow, making it more accessible than some diets used in previous studies.
“What may also be attractive to people is that you don’t have to wait for months to see an effect. If you start to consume a low-sodium diet, you can see results on blood pressure rapidly, within a week,” he said.
The diet in this study brought about a large reduction in dietary sodium, but Dr. Gupta says any reduction in dietary sodium is likely to be beneficial.
“If you go to the level that we got to, you could expect to see a reduction of around 6 mm Hg. But it’s like walking – you don’t necessarily need to get to 10,000 steps every day. Any amount of walking or physical activity is of benefit. The same is probably true for salt: Any reduction that you can make is probably of benefit.”
For the study, participants had their blood pressure measured by 24-hour ambulatory monitoring while on their usual diets. They were then randomly assigned to either a high-sodium diet or a low-sodium diet for 1 week. Participants then crossed over to the opposite diet for 1 week, with blood pressure measured over a 24-hour period on the last day of each diet.
As assessed by 24-hour urine excretion, the usual diet of participants was found to already be high in sodium (median, 4.45 g/d). This increased to a median of 5.00 g/d when on the high-sodium diet in the study and decreased to 1.27 g/d while on the low-sodium diet.
Results found participants had a median systolic blood pressure of 125 mm Hg on their usual diets. This was raised to 126 mm Hg on the high-sodium diet and lowered to 119 mm Hg on the low-sodium diet.
The researchers also reported that 75% of individuals showed a blood pressure reduction on the low-sodium diet and are thus defined as “salt-sensitive.” This is a higher percentage than found in previous studies.
“Of those that didn’t show a blood pressure reduction with a low-sodium diet in this study, it appears that they may not have been so adherent to the diet as those who did show a blood pressure reduction,” Dr. Gupta said.
He noted that hypertension is the most common chronic disease condition worldwide, with about 1.3 billion people affected, and although it has been known for some time that dietary sodium affects blood pressure, there have been some gaps in previous studies.
For example, many studies have excluded individuals who were already taking antihypertensive medications and people with diabetes, and they have generally not included many older individuals. The current study found that all of these groups showed significant blood pressure reductions by reducing dietary sodium.
Large effect in people with diabetes
Subgroup analysis largely showed consistent results across the population, regardless of age, sex, race, and body mass index and whether participants were taking antihypertensive medication or not, but there were a couple of exceptions. Individuals with higher blood pressure at baseline seemed to have a greater effect of lowering dietary sodium, although those who were normotensive at baseline still showed significant blood pressure reduction, Dr. Gupta reported.
The researchers found a particularly large reduction in blood pressure from lowering sodium intake in people with diabetes, who made up about 21% of the overall cohort. Their average reduction in systolic blood pressure between the high and low sodium diet was close to 17 mm Hg rather than the 7-8 mm Hg in the whole cohort.
Dr. Gupta said that the results are applicable to most of the population.
“The people who will be most motivated to follow a low-sodium diet are those with hypertension. But even in normotensive individuals, there is likely to be benefit.”
To help people follow a low-sodium diet, Dr. Gupta says education campaigns are needed “to show people that they can do it and make it work.” But there are bigger structural issues that need to be addressed at policy and governmental levels.
“Most of our food available in grocery stores and restaurants is high in salt. We now have a preponderance of evidence showing us that we need to change what’s available in the food supply,” he said. “There is a push going on for this now, and the U.S. has introduced some guidelines for the food industry on sodium content of foods. These are voluntary at this point, but it’s a start.”
Difficult to maintain long term
Commenting on the study, Paul Whelton, MD, chair in global public health at Tulane University, New Orleans, noted that sodium reduction is known to reduce blood pressure, with greater sodium reductions giving greater blood pressure decreases, and that some people are more sensitive to the effects of sodium than others.
He described CARDIA-SSBP as a “well-done study.”
“They managed to get a very low sodium intake and a large difference between the two groups, which translated into a big reduction in systolic blood pressure,” Dr. Whelton said. “However, the problem with these sorts of trials where the diets are provided to the participants is that although they show proof of concept, it is difficult to generalize because we can’t normally provide patients with their meals. In this type of ‘feeding’ study, we find it difficult to maintain people on their behavioral intervention over the long term.”
Dr. Whelton said that he was more excited about this trial knowing that the food given was commercially available. “That makes it more practical, but you still have to be quite motivated to follow a diet like this. Buying low-sodium products in the supermarket does require quite a lot of work to read the labels, and sometimes the low-sodium foods are specialty products and are more expensive.”
He pointed out that older people in higher socioeconomic classes are more likely to attempt this and do better from behavioral interventions in general. “Unfortunately, people who don’t do well from behavioral interventions like this are those from lower socioeconomic groups, who are ones at most at risk for cardiovascular disease.”
Dr. Whelton noted that the food industry has been reluctant to lower sodium content because high-salt foods sell better. “Unfortunately, foods high in saturated fat and salt taste good to most people. We are generally attuned to a high salt intake. But when people have been following a low-salt diet for a while, they generally don’t like high-salt foods anymore. They become attuned to lower-sodium diet,” he added.
New U.S. sodium reduction guidelines
Discussant of the CARDIA-SSBP study at the AHA meeting, Cheryl Anderson, MD, University of California, San Diego, said that the findings were important and consistent with prior studies.
“These studies have global implications because salt is ubiquitous in the food supply in much of the world,” she noted, adding that, “Americans consume almost 50% more sodium than recommended, and there has been a persistent lack of adherence to healthy diet recommendations for reductions in salt, sugar, and fats.”
Dr. Anderson pointed out that in 2021, the Food and Drug Administration issued guidance for voluntary sodium reduction, which uses a gradual approach, with targets to reach a population goal of 3,000 mg/d of sodium by 2023 and 2,300 mg/d by 2031.
“These targets apply to 150 categories of food that are sales-weighted to focus on dominant sellers in each category. They apply to food manufacturers, restaurants and food service operations,” she concluded. “These targets serve as a basis for continued dialogue. The research community eagerly awaits the review of population-based data to help refine this approach and goals.”
This study was supported by grants from the National Heart, Lung, and Blood Institute, the National Institutes of Health, the American Heart Association, and the National Center for Advancing Translational Sciences. The authors report no disclosures.
A version of this article appeared on Medscape.com.
FROM AHA 2023
Weight-loss drugs improve liver measures, too
BOSTON – With the current demand for type 2 diabetes drugs that both improve glycemic control and help patients shed large amounts of weight, liver specialists have speculated that the metabolic benefits could also extend to the liver.
Spoiler alert: they do.
, reported Takamasa Ohki, MD, PhD, and colleagues from the department of gastroenterology at Mitsui Memorial Hospital in Tokyo.
“Body weight reduction within 8 weeks after administration of these agents was an independent factor [that] contributed to rapid improvement of ALT. Maintenance of body weight and T2DM after normalization of ALT was also very important,” they wrote in a scientific poster presented at the annual meeting of the American Association for the Study of Liver Diseases.
The biggest losers benefit most
Dr. Ohki and colleagues evaluated the effectiveness of SGLT-2 inhibitors and GLP-1 agonists as treatment of MAFLD for patients with T2DM.
They conducted a retrospective study of 233 patients who had both conditions and who received either of the drug classes at their institution from June 2010 through December 2021; the most recent follow-up was in December 2022. The primary endpoint of the study was normalization of ALT values.
A total of 54 patients had a 3% or greater reduction in body weight within 8 weeks of beginning treatment with their respective drugs. The researchers found that for 47 of these patients (87%), ALT values normalized; the 12-, 24-, and 36-month cumulative normalization rates were 61%, 73%, and 80%, respectively.
In contrast, among the 179 patients who did not lose weight as robustly or rapidly, 137 (76.5%) demonstrated normalization of ALT, with cumulative normalization rates of 41%, 59% and 69%, respectively (P < .01).
In multivariate analysis that controlled for age, sex, smoking, hypertension, dyslipidemia, weight reduction, and antidiabetes drug use, body weight reduction of at least 3% within 8 weeks of beginning treatment with either an SLT-2 or GLP-1 agent was associated independently with normalization of ALT, with a hazard ratio (HR) of 0.67 (P = .028).
Improvement of T2DM was an independent predictor for ALT normalization (HR, 0.64; P = .015).
Other factors contributing to ALT normalization included use of sulfonylurea (HR, 0.63; P < .01) and insulin (HR, 0.54; P < .01).
In all, 103 of the 184 patients with initial normalization of ALT values experienced a recurrence of ALT elevation during follow-up. In multivariate analysis, body weight gain and exacerbation of T2DM were independent factors for ALT reexacerbation (HR, 0.52 and 0.48, respectively; P < .01 for both comparisons).
Duration of effect uncertain
Philip A. Newsome, PhD, FRCPE, professor of experimental hepatology and honorary consultant hepatologist at the University of Birmingham, England, who was not involved in the study, has conducted research into the metabolic effects of SGLT-2 inhibitors and GLP-1 agonists. In an interview, he said that both drug classes are likely to have positive near-term effects on metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through their effects on glucose control and reduction in associated comorbidities.
“The unknown question,” he added, is what will happen in the long term. “I think there are some uncertainties around what proportion of patients will essentially be downstaged or downgraded such that they don’t develop any other problem; I suspect that will be the case in very many patients. However, I suspect there will also be a large proportion that end up requiring additional therapy above and beyond weight loss,” said Dr. Newsome.
The investigators did not report a funding source for the study. Dr. Ohki and colleagues have disclosed no relevant financial relationships. Dr. Newsome has consulted on behalf of his institution with Novo Nordisk, BMS, Gilead, Pfizer, Poxel, and Intercept and has received a grant from Pharmaxis and Boehringer Ingelheim.
A version of this article appeared on Medscape.com.
BOSTON – With the current demand for type 2 diabetes drugs that both improve glycemic control and help patients shed large amounts of weight, liver specialists have speculated that the metabolic benefits could also extend to the liver.
Spoiler alert: they do.
, reported Takamasa Ohki, MD, PhD, and colleagues from the department of gastroenterology at Mitsui Memorial Hospital in Tokyo.
“Body weight reduction within 8 weeks after administration of these agents was an independent factor [that] contributed to rapid improvement of ALT. Maintenance of body weight and T2DM after normalization of ALT was also very important,” they wrote in a scientific poster presented at the annual meeting of the American Association for the Study of Liver Diseases.
The biggest losers benefit most
Dr. Ohki and colleagues evaluated the effectiveness of SGLT-2 inhibitors and GLP-1 agonists as treatment of MAFLD for patients with T2DM.
They conducted a retrospective study of 233 patients who had both conditions and who received either of the drug classes at their institution from June 2010 through December 2021; the most recent follow-up was in December 2022. The primary endpoint of the study was normalization of ALT values.
A total of 54 patients had a 3% or greater reduction in body weight within 8 weeks of beginning treatment with their respective drugs. The researchers found that for 47 of these patients (87%), ALT values normalized; the 12-, 24-, and 36-month cumulative normalization rates were 61%, 73%, and 80%, respectively.
In contrast, among the 179 patients who did not lose weight as robustly or rapidly, 137 (76.5%) demonstrated normalization of ALT, with cumulative normalization rates of 41%, 59% and 69%, respectively (P < .01).
In multivariate analysis that controlled for age, sex, smoking, hypertension, dyslipidemia, weight reduction, and antidiabetes drug use, body weight reduction of at least 3% within 8 weeks of beginning treatment with either an SLT-2 or GLP-1 agent was associated independently with normalization of ALT, with a hazard ratio (HR) of 0.67 (P = .028).
Improvement of T2DM was an independent predictor for ALT normalization (HR, 0.64; P = .015).
Other factors contributing to ALT normalization included use of sulfonylurea (HR, 0.63; P < .01) and insulin (HR, 0.54; P < .01).
In all, 103 of the 184 patients with initial normalization of ALT values experienced a recurrence of ALT elevation during follow-up. In multivariate analysis, body weight gain and exacerbation of T2DM were independent factors for ALT reexacerbation (HR, 0.52 and 0.48, respectively; P < .01 for both comparisons).
Duration of effect uncertain
Philip A. Newsome, PhD, FRCPE, professor of experimental hepatology and honorary consultant hepatologist at the University of Birmingham, England, who was not involved in the study, has conducted research into the metabolic effects of SGLT-2 inhibitors and GLP-1 agonists. In an interview, he said that both drug classes are likely to have positive near-term effects on metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through their effects on glucose control and reduction in associated comorbidities.
“The unknown question,” he added, is what will happen in the long term. “I think there are some uncertainties around what proportion of patients will essentially be downstaged or downgraded such that they don’t develop any other problem; I suspect that will be the case in very many patients. However, I suspect there will also be a large proportion that end up requiring additional therapy above and beyond weight loss,” said Dr. Newsome.
The investigators did not report a funding source for the study. Dr. Ohki and colleagues have disclosed no relevant financial relationships. Dr. Newsome has consulted on behalf of his institution with Novo Nordisk, BMS, Gilead, Pfizer, Poxel, and Intercept and has received a grant from Pharmaxis and Boehringer Ingelheim.
A version of this article appeared on Medscape.com.
BOSTON – With the current demand for type 2 diabetes drugs that both improve glycemic control and help patients shed large amounts of weight, liver specialists have speculated that the metabolic benefits could also extend to the liver.
Spoiler alert: they do.
, reported Takamasa Ohki, MD, PhD, and colleagues from the department of gastroenterology at Mitsui Memorial Hospital in Tokyo.
“Body weight reduction within 8 weeks after administration of these agents was an independent factor [that] contributed to rapid improvement of ALT. Maintenance of body weight and T2DM after normalization of ALT was also very important,” they wrote in a scientific poster presented at the annual meeting of the American Association for the Study of Liver Diseases.
The biggest losers benefit most
Dr. Ohki and colleagues evaluated the effectiveness of SGLT-2 inhibitors and GLP-1 agonists as treatment of MAFLD for patients with T2DM.
They conducted a retrospective study of 233 patients who had both conditions and who received either of the drug classes at their institution from June 2010 through December 2021; the most recent follow-up was in December 2022. The primary endpoint of the study was normalization of ALT values.
A total of 54 patients had a 3% or greater reduction in body weight within 8 weeks of beginning treatment with their respective drugs. The researchers found that for 47 of these patients (87%), ALT values normalized; the 12-, 24-, and 36-month cumulative normalization rates were 61%, 73%, and 80%, respectively.
In contrast, among the 179 patients who did not lose weight as robustly or rapidly, 137 (76.5%) demonstrated normalization of ALT, with cumulative normalization rates of 41%, 59% and 69%, respectively (P < .01).
In multivariate analysis that controlled for age, sex, smoking, hypertension, dyslipidemia, weight reduction, and antidiabetes drug use, body weight reduction of at least 3% within 8 weeks of beginning treatment with either an SLT-2 or GLP-1 agent was associated independently with normalization of ALT, with a hazard ratio (HR) of 0.67 (P = .028).
Improvement of T2DM was an independent predictor for ALT normalization (HR, 0.64; P = .015).
Other factors contributing to ALT normalization included use of sulfonylurea (HR, 0.63; P < .01) and insulin (HR, 0.54; P < .01).
In all, 103 of the 184 patients with initial normalization of ALT values experienced a recurrence of ALT elevation during follow-up. In multivariate analysis, body weight gain and exacerbation of T2DM were independent factors for ALT reexacerbation (HR, 0.52 and 0.48, respectively; P < .01 for both comparisons).
Duration of effect uncertain
Philip A. Newsome, PhD, FRCPE, professor of experimental hepatology and honorary consultant hepatologist at the University of Birmingham, England, who was not involved in the study, has conducted research into the metabolic effects of SGLT-2 inhibitors and GLP-1 agonists. In an interview, he said that both drug classes are likely to have positive near-term effects on metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through their effects on glucose control and reduction in associated comorbidities.
“The unknown question,” he added, is what will happen in the long term. “I think there are some uncertainties around what proportion of patients will essentially be downstaged or downgraded such that they don’t develop any other problem; I suspect that will be the case in very many patients. However, I suspect there will also be a large proportion that end up requiring additional therapy above and beyond weight loss,” said Dr. Newsome.
The investigators did not report a funding source for the study. Dr. Ohki and colleagues have disclosed no relevant financial relationships. Dr. Newsome has consulted on behalf of his institution with Novo Nordisk, BMS, Gilead, Pfizer, Poxel, and Intercept and has received a grant from Pharmaxis and Boehringer Ingelheim.
A version of this article appeared on Medscape.com.
AT THE LIVER MEETING
51-year-old woman • history of Graves disease • general fatigue, palpitations, and hand tremors • Dx?
THE CASE
A 51-year-old Japanese woman presented with fever, sore throat, and dyspnea of less than 1 day’s duration. Although she had developed general fatigue, palpitations, and tremors of the hands 2 months earlier, she had not sought medical care.
Her medical history included Graves disease, which had been diagnosed 13 years earlier. She reported that her only medication was methimazole 10 mg/d. She did not have any family history of endocrinopathies or hematologic diseases.
Physical examination revealed a body temperature of 99.7 °F; heart rate, 130 beats/min; blood pressure, 182/62 mm Hg; respiratory rate, 46 breaths/min; and oxygen saturation, 100% on room air. Pharyngeal erythema was seen. Lung sounds were clear. The patient had tremors in her hands, tenderness of the thyroid gland, and exophthalmos. No leg edema or jugular vein distension was seen.
Laboratory tests indicated hyperthyroidism, with a thyroid-stimulating hormone level < 0.01 µIU/mL (normal range, 0.5-5 µIU/mL); free T3 level, 4.87 pg/mL (normal range, 2.3-4.3 pg/mL); and free T4 level, 2.97 ng/dL (normal range, 0.9-1.7 ng/dL). The patient also had a white blood cell (WBC) count of 1020 cells/µL (normal range, 3500-9000 cells/µL) and neutrophil count of 5 cells/µL (normal range, 1500-6500 cells/µL).
Other blood cell counts were normal, and a chest x-ray did not reveal any abnormal findings. In addition, there was no evidence to suggest hematologic malignancies or congenital neutropenia.
THE DIAGNOSIS
Based on the patient’s low WBC and neutrophil counts, agranulocytosis due to antithyroid drug therapy was suspected; however, this diagnosis would be highly unusual in the context of a 13-year history of therapy. Further history taking revealed that, because of her lack of financial means, unstable living conditions, and lack of understanding of the necessity for medication adherence, the patient had not taken methimazole
In consideration of these factors, a diagnosis of exacerbation of hyperthyroidism and agranulocytosis (due to methimazole restart and upper respiratory infection) was made.
Continue to: DISCUSSION
DISCUSSION
Agranulocytosis is a severe adverse event of antithyroid agents and requires prompt diagnosis and treatment. In a 26-year study at one clinic, it occurred in approximately 0.4% of patients taking antithyroid agents.1 The possible mechanisms of agranulocytosis are the direct toxicity of drugs and immune-mediated responses.2 Older age, female sex, and some HLA genotypes are reported to be associated with susceptibility to agranulocytosis.2
Although the development of agranulocytosis tends to be dose related, a small dose of antithyroid agent can sometimes cause the condition.3,4 It usually occurs within the first 3 months of treatment initiation, but occasionally patients develop agranulocytosis after long-term therapy.5 Interruption and subsequent resumption of the same antithyroid drug treatment also can be a risk factor for agranulocytosis, as in this case.5
Treatment includes drug cessation, administration of broad-spectrum antibiotics if infection is suspected, and granulocyte-colony stimulating factor (G-CSF) therapy.5
Our patient was hospitalized, and methimazole was stopped immediately. Administration of potassium iodide 50 mg/d and G-CSF was started. Meropenem 3 g/d also was administered for neutropenic fever.
The patient’s condition improved, and her WBC count increased to 1640 cells/µL on Day 8 and 10,890 cells/µL on Day 9. G-CSF was stopped on Day 12 and meropenem on Day 13. Bone marrow aspiration was not performed because of improvement in lab values and her overall condition. Although monitoring of WBC count during methimazole therapy is controversial,5 we decided to routinely monitor this patient due to the possibility of drug cross-reactivity.
Continue to: Despite repeated explanations...
Despite repeated explanations that it was dangerous for a patient who had developed agranulocytosis to take another antithyroid medication, the patient refused surgical treatment or radioiodine ablation because of her financial situation. (While all Japanese citizens are covered by a national health insurance program, patients ages 6 to 70 years are required to pay approximately 30% of medical and pharmaceutical costs.) On Day 21, potassium iodide was stopped, and propylthiouracil 300 mg/d was administered with careful follow-up. Agranulocytosis did not recur.
Immediate problem solved, but what about the future?
During her hospital stay, the medical team spoke with the patient many times, during which she expressed anxiety about her health conditions and the difficulties that she had experienced in her life. The clinicians acknowledged her concerns and assured the patient of their continuing commitment to her well-being even after discharge. The patient also was advised that she should take her medication as prescribed and that if she had a fever or sore throat, she should stop the medication and seek medical care as soon as possible. The patient accepted the medical team’s advice and expressed hope for the future.
Conversations about medication adherence. In 1 survey, about 60% of patients taking antithyroid drugs were unfamiliar with the symptoms of agranulocytosis.6 To deliver safe and effective treatment and detect conditions such as agranulocytosis at an early stage, clinicians must communicate clearly with patients who have hyperthyroidism, providing sufficient explanation and ensuring understanding on the patient’s part.
Patients may be reluctant to provide the details of medication adherence.7 Although it is common for patients to need services for socioeconomic issues,8 health care professionals sometimes fail to adequately discuss these issues with patients, especially if the patients are marginalized and/or have lower economic status.9 Cases such as ours underscore the importance of improving clinicians’ awareness and sensitivity to patients’ socioeconomic challenges.10,11
Our patient received information about welfare and other government services from a medical social worker during her hospital stay. She also was informed that she could seek assistance from medical social workers in the future if needed.
Continue to: The patient was discharged...
The patient was discharged on Day 28. After discharge, she took propylthiouracil as prescribed (300 mg/d), and her Graves disease was well controlled. Outpatient follow-up visits were performed every 1 or 2 months. No adverse events of propylthiouracil were seen in the ensuing time.
THE TAKEAWAY
Patients with chronic conditions sometimes discontinue medications, and they may not talk about it with their medical team, especially if they have socioeconomic or other difficulties in their lives. Clinicians should consider medication nonadherence and its risk factors when patients with chronic conditions develop unexpected adverse events.
We thank Jane Charbonneau, DVM, from Edanz for doing an English-language review of a draft of this manuscript.
CORRESPONDENCE
Takuya Maejima, MD, Department of General Medicine and Primary Care, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki 305-8576 Japan; [email protected]
1. Tajiri J, Noguchi S. Antithyroid drug-induced agranulocytosis: special reference to normal white blood cell count agranulocytosis. Thyroid. 2004;14:459-462. doi: 10.1089/105072504323150787
2. Vicente N, Cardoso L, Barros L, et al. Antithyroid drug-induced agranulocytosis: state of the art on diagnosis and management. Drugs R D. 2017;17:91-96. doi: 10.1007/s40268-017-0172-1
3. Takata K, Kubota S, Fukata S, et al. Methimazole-induced agranulocytosis in patients with Graves’ disease is more frequent with an initial dose of 30 mg daily than with 15 mg daily. Thyroid. 2009;19:559-563. doi: 10.1089/thy.2008.0364
4. Tsuboi K, Ueshiba H, Shimojo M, et al. The relation of initial methimazole dose to the incidence of methimazole-induced agranulocytosis in patients with Graves’ disease. Endocr J. 2007;54:39-43. doi: 10.1507/endocrj.k05-068
5. Burch HB, Cooper DS. Management of Graves disease: a review. J Am Med Assoc. 2015;314:2544-2554. doi: 10.1001/jama.2015.16535
6. Robinson J, Richardson M, Hickey J, et al. Patient knowledge of antithyroid drug-induced agranulocytosis. Eur Thyroid J. 2014;3:245-251. doi: https://doi.org/10.1159/000367990
7. Kini V, Ho PM. Interventions to improve medication adherence: a review. J Am Med Assoc. 2018;320:2461-2473. doi: 10.1001/jama.2018.19271
8. Vest JR, Grannis SJ, Haut DP, et al. Using structured and unstructured data to identify patients’ need for services that address the social determinants of health. Int J Med Inform. 2017;107:101-106. doi: 10.1016/j.ijmedinf.2017.09.008
9. Willems S, De Maesschalck S, Deveugele M, et al. Socio-economic status of the patient and doctor-patient communication: does it make a difference? Patient Educ Couns. 2005;56:139-146. doi: 10.1016/j.pec.2004.02.011
10. The College of Family Physicians of Canada. Best advice: social determinants of health. Accessed September 15, 2023. https://patientsmedicalhome.ca/resources/best-advice-guides/best-advice-guide-social-determinants-health/
11. Hunter K, Thomson B. A scoping review of social determinants of health curricula in post-graduate medical education. Can Med Educ J. 2019;10:e61-e71. doi: 10.36834/cmej.61709
THE CASE
A 51-year-old Japanese woman presented with fever, sore throat, and dyspnea of less than 1 day’s duration. Although she had developed general fatigue, palpitations, and tremors of the hands 2 months earlier, she had not sought medical care.
Her medical history included Graves disease, which had been diagnosed 13 years earlier. She reported that her only medication was methimazole 10 mg/d. She did not have any family history of endocrinopathies or hematologic diseases.
Physical examination revealed a body temperature of 99.7 °F; heart rate, 130 beats/min; blood pressure, 182/62 mm Hg; respiratory rate, 46 breaths/min; and oxygen saturation, 100% on room air. Pharyngeal erythema was seen. Lung sounds were clear. The patient had tremors in her hands, tenderness of the thyroid gland, and exophthalmos. No leg edema or jugular vein distension was seen.
Laboratory tests indicated hyperthyroidism, with a thyroid-stimulating hormone level < 0.01 µIU/mL (normal range, 0.5-5 µIU/mL); free T3 level, 4.87 pg/mL (normal range, 2.3-4.3 pg/mL); and free T4 level, 2.97 ng/dL (normal range, 0.9-1.7 ng/dL). The patient also had a white blood cell (WBC) count of 1020 cells/µL (normal range, 3500-9000 cells/µL) and neutrophil count of 5 cells/µL (normal range, 1500-6500 cells/µL).
Other blood cell counts were normal, and a chest x-ray did not reveal any abnormal findings. In addition, there was no evidence to suggest hematologic malignancies or congenital neutropenia.
THE DIAGNOSIS
Based on the patient’s low WBC and neutrophil counts, agranulocytosis due to antithyroid drug therapy was suspected; however, this diagnosis would be highly unusual in the context of a 13-year history of therapy. Further history taking revealed that, because of her lack of financial means, unstable living conditions, and lack of understanding of the necessity for medication adherence, the patient had not taken methimazole
In consideration of these factors, a diagnosis of exacerbation of hyperthyroidism and agranulocytosis (due to methimazole restart and upper respiratory infection) was made.
Continue to: DISCUSSION
DISCUSSION
Agranulocytosis is a severe adverse event of antithyroid agents and requires prompt diagnosis and treatment. In a 26-year study at one clinic, it occurred in approximately 0.4% of patients taking antithyroid agents.1 The possible mechanisms of agranulocytosis are the direct toxicity of drugs and immune-mediated responses.2 Older age, female sex, and some HLA genotypes are reported to be associated with susceptibility to agranulocytosis.2
Although the development of agranulocytosis tends to be dose related, a small dose of antithyroid agent can sometimes cause the condition.3,4 It usually occurs within the first 3 months of treatment initiation, but occasionally patients develop agranulocytosis after long-term therapy.5 Interruption and subsequent resumption of the same antithyroid drug treatment also can be a risk factor for agranulocytosis, as in this case.5
Treatment includes drug cessation, administration of broad-spectrum antibiotics if infection is suspected, and granulocyte-colony stimulating factor (G-CSF) therapy.5
Our patient was hospitalized, and methimazole was stopped immediately. Administration of potassium iodide 50 mg/d and G-CSF was started. Meropenem 3 g/d also was administered for neutropenic fever.
The patient’s condition improved, and her WBC count increased to 1640 cells/µL on Day 8 and 10,890 cells/µL on Day 9. G-CSF was stopped on Day 12 and meropenem on Day 13. Bone marrow aspiration was not performed because of improvement in lab values and her overall condition. Although monitoring of WBC count during methimazole therapy is controversial,5 we decided to routinely monitor this patient due to the possibility of drug cross-reactivity.
Continue to: Despite repeated explanations...
Despite repeated explanations that it was dangerous for a patient who had developed agranulocytosis to take another antithyroid medication, the patient refused surgical treatment or radioiodine ablation because of her financial situation. (While all Japanese citizens are covered by a national health insurance program, patients ages 6 to 70 years are required to pay approximately 30% of medical and pharmaceutical costs.) On Day 21, potassium iodide was stopped, and propylthiouracil 300 mg/d was administered with careful follow-up. Agranulocytosis did not recur.
Immediate problem solved, but what about the future?
During her hospital stay, the medical team spoke with the patient many times, during which she expressed anxiety about her health conditions and the difficulties that she had experienced in her life. The clinicians acknowledged her concerns and assured the patient of their continuing commitment to her well-being even after discharge. The patient also was advised that she should take her medication as prescribed and that if she had a fever or sore throat, she should stop the medication and seek medical care as soon as possible. The patient accepted the medical team’s advice and expressed hope for the future.
Conversations about medication adherence. In 1 survey, about 60% of patients taking antithyroid drugs were unfamiliar with the symptoms of agranulocytosis.6 To deliver safe and effective treatment and detect conditions such as agranulocytosis at an early stage, clinicians must communicate clearly with patients who have hyperthyroidism, providing sufficient explanation and ensuring understanding on the patient’s part.
Patients may be reluctant to provide the details of medication adherence.7 Although it is common for patients to need services for socioeconomic issues,8 health care professionals sometimes fail to adequately discuss these issues with patients, especially if the patients are marginalized and/or have lower economic status.9 Cases such as ours underscore the importance of improving clinicians’ awareness and sensitivity to patients’ socioeconomic challenges.10,11
Our patient received information about welfare and other government services from a medical social worker during her hospital stay. She also was informed that she could seek assistance from medical social workers in the future if needed.
Continue to: The patient was discharged...
The patient was discharged on Day 28. After discharge, she took propylthiouracil as prescribed (300 mg/d), and her Graves disease was well controlled. Outpatient follow-up visits were performed every 1 or 2 months. No adverse events of propylthiouracil were seen in the ensuing time.
THE TAKEAWAY
Patients with chronic conditions sometimes discontinue medications, and they may not talk about it with their medical team, especially if they have socioeconomic or other difficulties in their lives. Clinicians should consider medication nonadherence and its risk factors when patients with chronic conditions develop unexpected adverse events.
We thank Jane Charbonneau, DVM, from Edanz for doing an English-language review of a draft of this manuscript.
CORRESPONDENCE
Takuya Maejima, MD, Department of General Medicine and Primary Care, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki 305-8576 Japan; [email protected]
THE CASE
A 51-year-old Japanese woman presented with fever, sore throat, and dyspnea of less than 1 day’s duration. Although she had developed general fatigue, palpitations, and tremors of the hands 2 months earlier, she had not sought medical care.
Her medical history included Graves disease, which had been diagnosed 13 years earlier. She reported that her only medication was methimazole 10 mg/d. She did not have any family history of endocrinopathies or hematologic diseases.
Physical examination revealed a body temperature of 99.7 °F; heart rate, 130 beats/min; blood pressure, 182/62 mm Hg; respiratory rate, 46 breaths/min; and oxygen saturation, 100% on room air. Pharyngeal erythema was seen. Lung sounds were clear. The patient had tremors in her hands, tenderness of the thyroid gland, and exophthalmos. No leg edema or jugular vein distension was seen.
Laboratory tests indicated hyperthyroidism, with a thyroid-stimulating hormone level < 0.01 µIU/mL (normal range, 0.5-5 µIU/mL); free T3 level, 4.87 pg/mL (normal range, 2.3-4.3 pg/mL); and free T4 level, 2.97 ng/dL (normal range, 0.9-1.7 ng/dL). The patient also had a white blood cell (WBC) count of 1020 cells/µL (normal range, 3500-9000 cells/µL) and neutrophil count of 5 cells/µL (normal range, 1500-6500 cells/µL).
Other blood cell counts were normal, and a chest x-ray did not reveal any abnormal findings. In addition, there was no evidence to suggest hematologic malignancies or congenital neutropenia.
THE DIAGNOSIS
Based on the patient’s low WBC and neutrophil counts, agranulocytosis due to antithyroid drug therapy was suspected; however, this diagnosis would be highly unusual in the context of a 13-year history of therapy. Further history taking revealed that, because of her lack of financial means, unstable living conditions, and lack of understanding of the necessity for medication adherence, the patient had not taken methimazole
In consideration of these factors, a diagnosis of exacerbation of hyperthyroidism and agranulocytosis (due to methimazole restart and upper respiratory infection) was made.
Continue to: DISCUSSION
DISCUSSION
Agranulocytosis is a severe adverse event of antithyroid agents and requires prompt diagnosis and treatment. In a 26-year study at one clinic, it occurred in approximately 0.4% of patients taking antithyroid agents.1 The possible mechanisms of agranulocytosis are the direct toxicity of drugs and immune-mediated responses.2 Older age, female sex, and some HLA genotypes are reported to be associated with susceptibility to agranulocytosis.2
Although the development of agranulocytosis tends to be dose related, a small dose of antithyroid agent can sometimes cause the condition.3,4 It usually occurs within the first 3 months of treatment initiation, but occasionally patients develop agranulocytosis after long-term therapy.5 Interruption and subsequent resumption of the same antithyroid drug treatment also can be a risk factor for agranulocytosis, as in this case.5
Treatment includes drug cessation, administration of broad-spectrum antibiotics if infection is suspected, and granulocyte-colony stimulating factor (G-CSF) therapy.5
Our patient was hospitalized, and methimazole was stopped immediately. Administration of potassium iodide 50 mg/d and G-CSF was started. Meropenem 3 g/d also was administered for neutropenic fever.
The patient’s condition improved, and her WBC count increased to 1640 cells/µL on Day 8 and 10,890 cells/µL on Day 9. G-CSF was stopped on Day 12 and meropenem on Day 13. Bone marrow aspiration was not performed because of improvement in lab values and her overall condition. Although monitoring of WBC count during methimazole therapy is controversial,5 we decided to routinely monitor this patient due to the possibility of drug cross-reactivity.
Continue to: Despite repeated explanations...
Despite repeated explanations that it was dangerous for a patient who had developed agranulocytosis to take another antithyroid medication, the patient refused surgical treatment or radioiodine ablation because of her financial situation. (While all Japanese citizens are covered by a national health insurance program, patients ages 6 to 70 years are required to pay approximately 30% of medical and pharmaceutical costs.) On Day 21, potassium iodide was stopped, and propylthiouracil 300 mg/d was administered with careful follow-up. Agranulocytosis did not recur.
Immediate problem solved, but what about the future?
During her hospital stay, the medical team spoke with the patient many times, during which she expressed anxiety about her health conditions and the difficulties that she had experienced in her life. The clinicians acknowledged her concerns and assured the patient of their continuing commitment to her well-being even after discharge. The patient also was advised that she should take her medication as prescribed and that if she had a fever or sore throat, she should stop the medication and seek medical care as soon as possible. The patient accepted the medical team’s advice and expressed hope for the future.
Conversations about medication adherence. In 1 survey, about 60% of patients taking antithyroid drugs were unfamiliar with the symptoms of agranulocytosis.6 To deliver safe and effective treatment and detect conditions such as agranulocytosis at an early stage, clinicians must communicate clearly with patients who have hyperthyroidism, providing sufficient explanation and ensuring understanding on the patient’s part.
Patients may be reluctant to provide the details of medication adherence.7 Although it is common for patients to need services for socioeconomic issues,8 health care professionals sometimes fail to adequately discuss these issues with patients, especially if the patients are marginalized and/or have lower economic status.9 Cases such as ours underscore the importance of improving clinicians’ awareness and sensitivity to patients’ socioeconomic challenges.10,11
Our patient received information about welfare and other government services from a medical social worker during her hospital stay. She also was informed that she could seek assistance from medical social workers in the future if needed.
Continue to: The patient was discharged...
The patient was discharged on Day 28. After discharge, she took propylthiouracil as prescribed (300 mg/d), and her Graves disease was well controlled. Outpatient follow-up visits were performed every 1 or 2 months. No adverse events of propylthiouracil were seen in the ensuing time.
THE TAKEAWAY
Patients with chronic conditions sometimes discontinue medications, and they may not talk about it with their medical team, especially if they have socioeconomic or other difficulties in their lives. Clinicians should consider medication nonadherence and its risk factors when patients with chronic conditions develop unexpected adverse events.
We thank Jane Charbonneau, DVM, from Edanz for doing an English-language review of a draft of this manuscript.
CORRESPONDENCE
Takuya Maejima, MD, Department of General Medicine and Primary Care, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki 305-8576 Japan; [email protected]
1. Tajiri J, Noguchi S. Antithyroid drug-induced agranulocytosis: special reference to normal white blood cell count agranulocytosis. Thyroid. 2004;14:459-462. doi: 10.1089/105072504323150787
2. Vicente N, Cardoso L, Barros L, et al. Antithyroid drug-induced agranulocytosis: state of the art on diagnosis and management. Drugs R D. 2017;17:91-96. doi: 10.1007/s40268-017-0172-1
3. Takata K, Kubota S, Fukata S, et al. Methimazole-induced agranulocytosis in patients with Graves’ disease is more frequent with an initial dose of 30 mg daily than with 15 mg daily. Thyroid. 2009;19:559-563. doi: 10.1089/thy.2008.0364
4. Tsuboi K, Ueshiba H, Shimojo M, et al. The relation of initial methimazole dose to the incidence of methimazole-induced agranulocytosis in patients with Graves’ disease. Endocr J. 2007;54:39-43. doi: 10.1507/endocrj.k05-068
5. Burch HB, Cooper DS. Management of Graves disease: a review. J Am Med Assoc. 2015;314:2544-2554. doi: 10.1001/jama.2015.16535
6. Robinson J, Richardson M, Hickey J, et al. Patient knowledge of antithyroid drug-induced agranulocytosis. Eur Thyroid J. 2014;3:245-251. doi: https://doi.org/10.1159/000367990
7. Kini V, Ho PM. Interventions to improve medication adherence: a review. J Am Med Assoc. 2018;320:2461-2473. doi: 10.1001/jama.2018.19271
8. Vest JR, Grannis SJ, Haut DP, et al. Using structured and unstructured data to identify patients’ need for services that address the social determinants of health. Int J Med Inform. 2017;107:101-106. doi: 10.1016/j.ijmedinf.2017.09.008
9. Willems S, De Maesschalck S, Deveugele M, et al. Socio-economic status of the patient and doctor-patient communication: does it make a difference? Patient Educ Couns. 2005;56:139-146. doi: 10.1016/j.pec.2004.02.011
10. The College of Family Physicians of Canada. Best advice: social determinants of health. Accessed September 15, 2023. https://patientsmedicalhome.ca/resources/best-advice-guides/best-advice-guide-social-determinants-health/
11. Hunter K, Thomson B. A scoping review of social determinants of health curricula in post-graduate medical education. Can Med Educ J. 2019;10:e61-e71. doi: 10.36834/cmej.61709
1. Tajiri J, Noguchi S. Antithyroid drug-induced agranulocytosis: special reference to normal white blood cell count agranulocytosis. Thyroid. 2004;14:459-462. doi: 10.1089/105072504323150787
2. Vicente N, Cardoso L, Barros L, et al. Antithyroid drug-induced agranulocytosis: state of the art on diagnosis and management. Drugs R D. 2017;17:91-96. doi: 10.1007/s40268-017-0172-1
3. Takata K, Kubota S, Fukata S, et al. Methimazole-induced agranulocytosis in patients with Graves’ disease is more frequent with an initial dose of 30 mg daily than with 15 mg daily. Thyroid. 2009;19:559-563. doi: 10.1089/thy.2008.0364
4. Tsuboi K, Ueshiba H, Shimojo M, et al. The relation of initial methimazole dose to the incidence of methimazole-induced agranulocytosis in patients with Graves’ disease. Endocr J. 2007;54:39-43. doi: 10.1507/endocrj.k05-068
5. Burch HB, Cooper DS. Management of Graves disease: a review. J Am Med Assoc. 2015;314:2544-2554. doi: 10.1001/jama.2015.16535
6. Robinson J, Richardson M, Hickey J, et al. Patient knowledge of antithyroid drug-induced agranulocytosis. Eur Thyroid J. 2014;3:245-251. doi: https://doi.org/10.1159/000367990
7. Kini V, Ho PM. Interventions to improve medication adherence: a review. J Am Med Assoc. 2018;320:2461-2473. doi: 10.1001/jama.2018.19271
8. Vest JR, Grannis SJ, Haut DP, et al. Using structured and unstructured data to identify patients’ need for services that address the social determinants of health. Int J Med Inform. 2017;107:101-106. doi: 10.1016/j.ijmedinf.2017.09.008
9. Willems S, De Maesschalck S, Deveugele M, et al. Socio-economic status of the patient and doctor-patient communication: does it make a difference? Patient Educ Couns. 2005;56:139-146. doi: 10.1016/j.pec.2004.02.011
10. The College of Family Physicians of Canada. Best advice: social determinants of health. Accessed September 15, 2023. https://patientsmedicalhome.ca/resources/best-advice-guides/best-advice-guide-social-determinants-health/
11. Hunter K, Thomson B. A scoping review of social determinants of health curricula in post-graduate medical education. Can Med Educ J. 2019;10:e61-e71. doi: 10.36834/cmej.61709
► History of Graves disease
► General fatigue, palpitations, and hand tremors
Painless nodules on legs
A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radioiodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).
Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Pretibial myxedema
The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A). The spaces contained basophilic strands (FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.
The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid1 and obstructing lymphatic microcirculation, resulting in nonpitting edema.2
There are 5 distinct clinical variants of pretibial myxedema1,3:
- The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
- The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
- The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
- The mixed form manifests as 2 or more of the other variants.
- The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.
A rare, late manifestation
Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.4 The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.4
While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.5
Continue to: More serious conditions must be ruled out
More serious conditions must be ruled out
The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.
Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma (PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,6 differing from our case.
Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.
Treatment is simple and noninvasive
Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intralesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.2
This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.
1. Thammarucha S, Sudtikoonaseth P. Nodular pretibial myxedema with Graves’ disease: a case report. Thai J Dermatol. 2021;37:30-36.
2. Singla M, Gupta A. Nodular thyroid dermopathy: not a hallmark of Graves’ disease. Am J Med. 2019;132:e521-e522. doi: 10.1016/j.amjmed.2018.11.004
3. Lan C, Wang Y, Zeng X, et al. Morphological diversity of pretibial myxedema and its mechanism of evolving process and outcome: a retrospective study of 216 cases. J Thyroid Res. 2016:2016:265217
4. doi: 10.1155/2016/2652174 4. Patil MM, Kamalanathan S, Sahoo J, et al. Pretibial myxedema. QJM. 2015;108:985. doi: 10.1093/qjmed/hcv136
5. Harvey RD, Metcalfe RA, Morteo C, et al. Acute pre-tibial myxoedema following radioiodine therapy for thyrotoxic Graves’ disease. Clin Endocrinol (Oxf). 1995;42:657-660. doi: 10.1111/j.1365-2265.1995.tb02695.x
6. Schukow C, Ahmed A. Dermatopathology, cutaneous lymphomas. StatPearls [Internet]. Updated February 16, 2023. Accessed October 23, 2023. www.ncbi.nlm.nih.gov/books/NBK589703/
A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radioiodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).
Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Pretibial myxedema
The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A). The spaces contained basophilic strands (FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.
The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid1 and obstructing lymphatic microcirculation, resulting in nonpitting edema.2
There are 5 distinct clinical variants of pretibial myxedema1,3:
- The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
- The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
- The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
- The mixed form manifests as 2 or more of the other variants.
- The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.
A rare, late manifestation
Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.4 The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.4
While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.5
Continue to: More serious conditions must be ruled out
More serious conditions must be ruled out
The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.
Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma (PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,6 differing from our case.
Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.
Treatment is simple and noninvasive
Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intralesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.2
This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.
A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radioiodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).
Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Pretibial myxedema
The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A). The spaces contained basophilic strands (FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.
The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid1 and obstructing lymphatic microcirculation, resulting in nonpitting edema.2
There are 5 distinct clinical variants of pretibial myxedema1,3:
- The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
- The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
- The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
- The mixed form manifests as 2 or more of the other variants.
- The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.
A rare, late manifestation
Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.4 The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.4
While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.5
Continue to: More serious conditions must be ruled out
More serious conditions must be ruled out
The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.
Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma (PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,6 differing from our case.
Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.
Treatment is simple and noninvasive
Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intralesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.2
This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.
1. Thammarucha S, Sudtikoonaseth P. Nodular pretibial myxedema with Graves’ disease: a case report. Thai J Dermatol. 2021;37:30-36.
2. Singla M, Gupta A. Nodular thyroid dermopathy: not a hallmark of Graves’ disease. Am J Med. 2019;132:e521-e522. doi: 10.1016/j.amjmed.2018.11.004
3. Lan C, Wang Y, Zeng X, et al. Morphological diversity of pretibial myxedema and its mechanism of evolving process and outcome: a retrospective study of 216 cases. J Thyroid Res. 2016:2016:265217
4. doi: 10.1155/2016/2652174 4. Patil MM, Kamalanathan S, Sahoo J, et al. Pretibial myxedema. QJM. 2015;108:985. doi: 10.1093/qjmed/hcv136
5. Harvey RD, Metcalfe RA, Morteo C, et al. Acute pre-tibial myxoedema following radioiodine therapy for thyrotoxic Graves’ disease. Clin Endocrinol (Oxf). 1995;42:657-660. doi: 10.1111/j.1365-2265.1995.tb02695.x
6. Schukow C, Ahmed A. Dermatopathology, cutaneous lymphomas. StatPearls [Internet]. Updated February 16, 2023. Accessed October 23, 2023. www.ncbi.nlm.nih.gov/books/NBK589703/
1. Thammarucha S, Sudtikoonaseth P. Nodular pretibial myxedema with Graves’ disease: a case report. Thai J Dermatol. 2021;37:30-36.
2. Singla M, Gupta A. Nodular thyroid dermopathy: not a hallmark of Graves’ disease. Am J Med. 2019;132:e521-e522. doi: 10.1016/j.amjmed.2018.11.004
3. Lan C, Wang Y, Zeng X, et al. Morphological diversity of pretibial myxedema and its mechanism of evolving process and outcome: a retrospective study of 216 cases. J Thyroid Res. 2016:2016:265217
4. doi: 10.1155/2016/2652174 4. Patil MM, Kamalanathan S, Sahoo J, et al. Pretibial myxedema. QJM. 2015;108:985. doi: 10.1093/qjmed/hcv136
5. Harvey RD, Metcalfe RA, Morteo C, et al. Acute pre-tibial myxoedema following radioiodine therapy for thyrotoxic Graves’ disease. Clin Endocrinol (Oxf). 1995;42:657-660. doi: 10.1111/j.1365-2265.1995.tb02695.x
6. Schukow C, Ahmed A. Dermatopathology, cutaneous lymphomas. StatPearls [Internet]. Updated February 16, 2023. Accessed October 23, 2023. www.ncbi.nlm.nih.gov/books/NBK589703/
AI algorithm aids egg retrieval date during fertility treatment cycles
According to the researchers, such an algorithm is needed due to the increased demand for fertility treatments, as well as the high day-to-day variability in lab workload.
According to the study investigators, predicting retrieval dates in advance for ongoing cycles is of major importance for both patients and clinicians.
“The population requiring fertility treatments, including genetic testing and fertility preservation, has massively increased, and this causes many more cycles and a high day-to-day variability in IVF activity, especially in the lab workload,” said Rohi Hourvitz, MBA, from FertilAI, an Israeli health care company focused on developing technologies that improve fertility treatments.
“We also need to accommodate and reschedule for non-working days, which causes a big issue with managing the workload in many clinics around the world,” added Mr. Hourvitz, who presented the research highlighting AI’s growing role in reproductive medicine.
In addition, AI has recently emerged as an effective tool for assisting in clinical decision-making in assisted reproductive technology, prompting further research in this space, he said.
The new study used a dataset of 9,550 predictable antagonist cycles (defined as having all necessary data) gathered from one lab with over 50 physicians between August 2018 and October 2022. The data were split into two subsets: one for training the AI model and the other for prospective testing.
To train and test the AI model, data from nearly 6,000 predictable antagonist cycles were used. Key factors used for each cycle included estrogen levels, mean follicle size, primary follicle size, and various patient demographics. Other features were considered, but Mr. Hourvitz noted that primary follicle size influenced the algorithm most, “because that is what most of us use when we want to trigger.”
Mr. Hourvitz explained that these patient data were run through an algorithm that produced a graph predicting the most probable date for a cycle retrieval.
“We could accurately predict when those ‘peak days’ were going to be happening in the clinic, and we could also give a pretty good estimate on how many cycles you’re going to have every day,” Mr. Hourvitz said, explaining that this information could help clinics more efficiently allocate resources and manage patients.
According to Mr. Hourvitz, the predictions derived from this study could improve various aspects of fertility treatments and related procedures, including better staff planning and caseload management in IVF labs, as well as higher-quality eggs at retrieval. Patients would have a clearer timeline for their treatment cycles.
Nikica Zaninovic, PhD, MS, director of the embryology lab at Weill Cornell Medical College, New York City, cautioned that the new findings are not yet ready for clinical application but emphasized the importance of more AI research focusing on the quality of oocytes, not only embryos.
“We’re so focused on the end of the process: the embryo,” Dr. Zaninovic, who was not involved in the research, said in an interview. “I think the focus should be on the beginning – the quality of eggs and sperm, not just the quantity – because that’s what the embryos will depend on.”
He noted the increasing numbers of young women in the United States undergoing egg freezing.
“Cornell is the largest academic IVF center in the United States; 20%-30% of all of the patients that we treat are actually freezing their eggs,” he said. “It’s a huge population.”
“When they come to us, they ask how many eggs they’ll need to guarantee one or two children in the future,” Dr. Zaninovic continued. “We don’t have that answer, so we always tell them [we’ll retrieve] as many as we can. That’s not the answer; we need to be more precise. We’re still lacking these tools, and I think that’s where the research will go.”
The study was funded by FertilAI. Mr. Hourvitz is a shareholder and CEO of FertilAI. Dr. Zaninovic is president of the AI Fertility Society.
A version of this article appeared on Medscape.com.
According to the researchers, such an algorithm is needed due to the increased demand for fertility treatments, as well as the high day-to-day variability in lab workload.
According to the study investigators, predicting retrieval dates in advance for ongoing cycles is of major importance for both patients and clinicians.
“The population requiring fertility treatments, including genetic testing and fertility preservation, has massively increased, and this causes many more cycles and a high day-to-day variability in IVF activity, especially in the lab workload,” said Rohi Hourvitz, MBA, from FertilAI, an Israeli health care company focused on developing technologies that improve fertility treatments.
“We also need to accommodate and reschedule for non-working days, which causes a big issue with managing the workload in many clinics around the world,” added Mr. Hourvitz, who presented the research highlighting AI’s growing role in reproductive medicine.
In addition, AI has recently emerged as an effective tool for assisting in clinical decision-making in assisted reproductive technology, prompting further research in this space, he said.
The new study used a dataset of 9,550 predictable antagonist cycles (defined as having all necessary data) gathered from one lab with over 50 physicians between August 2018 and October 2022. The data were split into two subsets: one for training the AI model and the other for prospective testing.
To train and test the AI model, data from nearly 6,000 predictable antagonist cycles were used. Key factors used for each cycle included estrogen levels, mean follicle size, primary follicle size, and various patient demographics. Other features were considered, but Mr. Hourvitz noted that primary follicle size influenced the algorithm most, “because that is what most of us use when we want to trigger.”
Mr. Hourvitz explained that these patient data were run through an algorithm that produced a graph predicting the most probable date for a cycle retrieval.
“We could accurately predict when those ‘peak days’ were going to be happening in the clinic, and we could also give a pretty good estimate on how many cycles you’re going to have every day,” Mr. Hourvitz said, explaining that this information could help clinics more efficiently allocate resources and manage patients.
According to Mr. Hourvitz, the predictions derived from this study could improve various aspects of fertility treatments and related procedures, including better staff planning and caseload management in IVF labs, as well as higher-quality eggs at retrieval. Patients would have a clearer timeline for their treatment cycles.
Nikica Zaninovic, PhD, MS, director of the embryology lab at Weill Cornell Medical College, New York City, cautioned that the new findings are not yet ready for clinical application but emphasized the importance of more AI research focusing on the quality of oocytes, not only embryos.
“We’re so focused on the end of the process: the embryo,” Dr. Zaninovic, who was not involved in the research, said in an interview. “I think the focus should be on the beginning – the quality of eggs and sperm, not just the quantity – because that’s what the embryos will depend on.”
He noted the increasing numbers of young women in the United States undergoing egg freezing.
“Cornell is the largest academic IVF center in the United States; 20%-30% of all of the patients that we treat are actually freezing their eggs,” he said. “It’s a huge population.”
“When they come to us, they ask how many eggs they’ll need to guarantee one or two children in the future,” Dr. Zaninovic continued. “We don’t have that answer, so we always tell them [we’ll retrieve] as many as we can. That’s not the answer; we need to be more precise. We’re still lacking these tools, and I think that’s where the research will go.”
The study was funded by FertilAI. Mr. Hourvitz is a shareholder and CEO of FertilAI. Dr. Zaninovic is president of the AI Fertility Society.
A version of this article appeared on Medscape.com.
According to the researchers, such an algorithm is needed due to the increased demand for fertility treatments, as well as the high day-to-day variability in lab workload.
According to the study investigators, predicting retrieval dates in advance for ongoing cycles is of major importance for both patients and clinicians.
“The population requiring fertility treatments, including genetic testing and fertility preservation, has massively increased, and this causes many more cycles and a high day-to-day variability in IVF activity, especially in the lab workload,” said Rohi Hourvitz, MBA, from FertilAI, an Israeli health care company focused on developing technologies that improve fertility treatments.
“We also need to accommodate and reschedule for non-working days, which causes a big issue with managing the workload in many clinics around the world,” added Mr. Hourvitz, who presented the research highlighting AI’s growing role in reproductive medicine.
In addition, AI has recently emerged as an effective tool for assisting in clinical decision-making in assisted reproductive technology, prompting further research in this space, he said.
The new study used a dataset of 9,550 predictable antagonist cycles (defined as having all necessary data) gathered from one lab with over 50 physicians between August 2018 and October 2022. The data were split into two subsets: one for training the AI model and the other for prospective testing.
To train and test the AI model, data from nearly 6,000 predictable antagonist cycles were used. Key factors used for each cycle included estrogen levels, mean follicle size, primary follicle size, and various patient demographics. Other features were considered, but Mr. Hourvitz noted that primary follicle size influenced the algorithm most, “because that is what most of us use when we want to trigger.”
Mr. Hourvitz explained that these patient data were run through an algorithm that produced a graph predicting the most probable date for a cycle retrieval.
“We could accurately predict when those ‘peak days’ were going to be happening in the clinic, and we could also give a pretty good estimate on how many cycles you’re going to have every day,” Mr. Hourvitz said, explaining that this information could help clinics more efficiently allocate resources and manage patients.
According to Mr. Hourvitz, the predictions derived from this study could improve various aspects of fertility treatments and related procedures, including better staff planning and caseload management in IVF labs, as well as higher-quality eggs at retrieval. Patients would have a clearer timeline for their treatment cycles.
Nikica Zaninovic, PhD, MS, director of the embryology lab at Weill Cornell Medical College, New York City, cautioned that the new findings are not yet ready for clinical application but emphasized the importance of more AI research focusing on the quality of oocytes, not only embryos.
“We’re so focused on the end of the process: the embryo,” Dr. Zaninovic, who was not involved in the research, said in an interview. “I think the focus should be on the beginning – the quality of eggs and sperm, not just the quantity – because that’s what the embryos will depend on.”
He noted the increasing numbers of young women in the United States undergoing egg freezing.
“Cornell is the largest academic IVF center in the United States; 20%-30% of all of the patients that we treat are actually freezing their eggs,” he said. “It’s a huge population.”
“When they come to us, they ask how many eggs they’ll need to guarantee one or two children in the future,” Dr. Zaninovic continued. “We don’t have that answer, so we always tell them [we’ll retrieve] as many as we can. That’s not the answer; we need to be more precise. We’re still lacking these tools, and I think that’s where the research will go.”
The study was funded by FertilAI. Mr. Hourvitz is a shareholder and CEO of FertilAI. Dr. Zaninovic is president of the AI Fertility Society.
A version of this article appeared on Medscape.com.
FROM ASRM 2023
Pervasive ‘forever chemicals’ linked to thyroid cancer?
The study suggests that higher exposure to per- and polyfluoroalkyl substances (PFAS), specifically perfluorooctanesulfonic acid (n-PFOS), may increase a person’s risk for thyroid cancer by 56%.
Several news outlets played up the findings, published online in eBioMedicine. “Dangerous ‘Forever Chemicals’ in Your Everyday Items Are Causing Cancer,” Newsweek reported.
But Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong (Australia), voiced his skepticism.
“While it’s possible that PFAS might be causing thyroid cancer, the evidence thus far is unconvincing and probably not worth worrying about,” said Dr. Meyerowitz-Katz, who was not involved in the research.
PFAS and thyroid cancer
PFAS are a class of widely used synthetic chemicals found in many consumer and industrial products, including nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam.
These substances have been dubbed “forever chemicals” because they do not degrade and are ubiquitous in the environment.
Exposure to endocrine-disrupting chemicals, including PFAS, has been identified as a potential risk factor for thyroid cancer, with some research linking PFAS exposure to thyroid dysfunction and carcinogenesis.
To investigate further, the researchers performed a nested case-control study of 86 patients with thyroid cancer using plasma samples collected at or before diagnosis and 86 controls without cancer who were matched on age, sex, race/ethnicity, body weight, smoking status, and year of sample collection.
Eighteen individual PFAS were measured in plasma samples; 10 were undetectable and were therefore excluded from the analysis. Of the remaining eight PFAS, only one showed a statistically significant correlation with thyroid cancer.
Specifically, the researchers found that exposure to n-PFOS was associated with a 56% increased risk for thyroid cancer among people who had a high level of the chemical in their blood (adjusted odds ratio, 1.56; P = .004). The results were similar when patients with papillary thyroid cancer only were included (aOR, 1.56; P = .009).
A separate longitudinal analysis of 31 patients diagnosed with thyroid cancer 1 year or more after plasma sample collection and 31 controls confirmed the positive association between n-PFOS and thyroid cancer (aOR, 2.67; P < .001). The longitudinal analysis also suggested correlations for a few other PFAS.
“This study supports the hypothesis that PFAS exposure may be associated with increased risk of thyroid cancer,” the authors concluded.
But in a Substack post, Dr. Meyerowitz-Katz said that it’s important to put the findings into “proper context before getting terrified about this all-new cancer risk.”
First, this study was “genuinely tiny,” with data on just 88 people with thyroid cancer and 88 controls, a limitation the researchers also acknowledged.
“That’s really not enough to do any sort of robust epidemiological analysis – you can generate interesting correlations, but what those correlations mean is anyone’s guess,” Dr. Meyerowitz-Katz said.
Even more importantly, one could easily argue that the results of this study show that most PFAS aren’t associated with thyroid cancer, given that there was no strong association for seven of the eight PFAS measured, he explained.
“There are no serious methodological concerns here, but equally there’s just not much you can reasonably gather from finding a single correlation among a vast ocean of possibilities,” Dr. Meyerowitz-Katz wrote. “Maybe there’s a correlation there, but you’d need to investigate this in much bigger samples, with more controls, and better data, to understand what that correlation means.”
Bottom line, Dr. Meyerowitz-Katz explained, is that “the link between PFAS and thyroid cancer is, at best, incredibly weak.”
Funding for the study was provided by the National Institutes of Health and The Andrea and Charles Bronfman Philanthropies. One coauthor is cofounder of Linus Biotechnology and is owner of a license agreement with NIES (Japan); received honoraria and travel compensation for lectures for the Bio-Echo and Brin foundations; and has 22 patents at various stages. Dr. Meyerowitz-Katz has no relevant disclosures.
A version of this article appeared on Medscape.com.
The study suggests that higher exposure to per- and polyfluoroalkyl substances (PFAS), specifically perfluorooctanesulfonic acid (n-PFOS), may increase a person’s risk for thyroid cancer by 56%.
Several news outlets played up the findings, published online in eBioMedicine. “Dangerous ‘Forever Chemicals’ in Your Everyday Items Are Causing Cancer,” Newsweek reported.
But Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong (Australia), voiced his skepticism.
“While it’s possible that PFAS might be causing thyroid cancer, the evidence thus far is unconvincing and probably not worth worrying about,” said Dr. Meyerowitz-Katz, who was not involved in the research.
PFAS and thyroid cancer
PFAS are a class of widely used synthetic chemicals found in many consumer and industrial products, including nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam.
These substances have been dubbed “forever chemicals” because they do not degrade and are ubiquitous in the environment.
Exposure to endocrine-disrupting chemicals, including PFAS, has been identified as a potential risk factor for thyroid cancer, with some research linking PFAS exposure to thyroid dysfunction and carcinogenesis.
To investigate further, the researchers performed a nested case-control study of 86 patients with thyroid cancer using plasma samples collected at or before diagnosis and 86 controls without cancer who were matched on age, sex, race/ethnicity, body weight, smoking status, and year of sample collection.
Eighteen individual PFAS were measured in plasma samples; 10 were undetectable and were therefore excluded from the analysis. Of the remaining eight PFAS, only one showed a statistically significant correlation with thyroid cancer.
Specifically, the researchers found that exposure to n-PFOS was associated with a 56% increased risk for thyroid cancer among people who had a high level of the chemical in their blood (adjusted odds ratio, 1.56; P = .004). The results were similar when patients with papillary thyroid cancer only were included (aOR, 1.56; P = .009).
A separate longitudinal analysis of 31 patients diagnosed with thyroid cancer 1 year or more after plasma sample collection and 31 controls confirmed the positive association between n-PFOS and thyroid cancer (aOR, 2.67; P < .001). The longitudinal analysis also suggested correlations for a few other PFAS.
“This study supports the hypothesis that PFAS exposure may be associated with increased risk of thyroid cancer,” the authors concluded.
But in a Substack post, Dr. Meyerowitz-Katz said that it’s important to put the findings into “proper context before getting terrified about this all-new cancer risk.”
First, this study was “genuinely tiny,” with data on just 88 people with thyroid cancer and 88 controls, a limitation the researchers also acknowledged.
“That’s really not enough to do any sort of robust epidemiological analysis – you can generate interesting correlations, but what those correlations mean is anyone’s guess,” Dr. Meyerowitz-Katz said.
Even more importantly, one could easily argue that the results of this study show that most PFAS aren’t associated with thyroid cancer, given that there was no strong association for seven of the eight PFAS measured, he explained.
“There are no serious methodological concerns here, but equally there’s just not much you can reasonably gather from finding a single correlation among a vast ocean of possibilities,” Dr. Meyerowitz-Katz wrote. “Maybe there’s a correlation there, but you’d need to investigate this in much bigger samples, with more controls, and better data, to understand what that correlation means.”
Bottom line, Dr. Meyerowitz-Katz explained, is that “the link between PFAS and thyroid cancer is, at best, incredibly weak.”
Funding for the study was provided by the National Institutes of Health and The Andrea and Charles Bronfman Philanthropies. One coauthor is cofounder of Linus Biotechnology and is owner of a license agreement with NIES (Japan); received honoraria and travel compensation for lectures for the Bio-Echo and Brin foundations; and has 22 patents at various stages. Dr. Meyerowitz-Katz has no relevant disclosures.
A version of this article appeared on Medscape.com.
The study suggests that higher exposure to per- and polyfluoroalkyl substances (PFAS), specifically perfluorooctanesulfonic acid (n-PFOS), may increase a person’s risk for thyroid cancer by 56%.
Several news outlets played up the findings, published online in eBioMedicine. “Dangerous ‘Forever Chemicals’ in Your Everyday Items Are Causing Cancer,” Newsweek reported.
But Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong (Australia), voiced his skepticism.
“While it’s possible that PFAS might be causing thyroid cancer, the evidence thus far is unconvincing and probably not worth worrying about,” said Dr. Meyerowitz-Katz, who was not involved in the research.
PFAS and thyroid cancer
PFAS are a class of widely used synthetic chemicals found in many consumer and industrial products, including nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam.
These substances have been dubbed “forever chemicals” because they do not degrade and are ubiquitous in the environment.
Exposure to endocrine-disrupting chemicals, including PFAS, has been identified as a potential risk factor for thyroid cancer, with some research linking PFAS exposure to thyroid dysfunction and carcinogenesis.
To investigate further, the researchers performed a nested case-control study of 86 patients with thyroid cancer using plasma samples collected at or before diagnosis and 86 controls without cancer who were matched on age, sex, race/ethnicity, body weight, smoking status, and year of sample collection.
Eighteen individual PFAS were measured in plasma samples; 10 were undetectable and were therefore excluded from the analysis. Of the remaining eight PFAS, only one showed a statistically significant correlation with thyroid cancer.
Specifically, the researchers found that exposure to n-PFOS was associated with a 56% increased risk for thyroid cancer among people who had a high level of the chemical in their blood (adjusted odds ratio, 1.56; P = .004). The results were similar when patients with papillary thyroid cancer only were included (aOR, 1.56; P = .009).
A separate longitudinal analysis of 31 patients diagnosed with thyroid cancer 1 year or more after plasma sample collection and 31 controls confirmed the positive association between n-PFOS and thyroid cancer (aOR, 2.67; P < .001). The longitudinal analysis also suggested correlations for a few other PFAS.
“This study supports the hypothesis that PFAS exposure may be associated with increased risk of thyroid cancer,” the authors concluded.
But in a Substack post, Dr. Meyerowitz-Katz said that it’s important to put the findings into “proper context before getting terrified about this all-new cancer risk.”
First, this study was “genuinely tiny,” with data on just 88 people with thyroid cancer and 88 controls, a limitation the researchers also acknowledged.
“That’s really not enough to do any sort of robust epidemiological analysis – you can generate interesting correlations, but what those correlations mean is anyone’s guess,” Dr. Meyerowitz-Katz said.
Even more importantly, one could easily argue that the results of this study show that most PFAS aren’t associated with thyroid cancer, given that there was no strong association for seven of the eight PFAS measured, he explained.
“There are no serious methodological concerns here, but equally there’s just not much you can reasonably gather from finding a single correlation among a vast ocean of possibilities,” Dr. Meyerowitz-Katz wrote. “Maybe there’s a correlation there, but you’d need to investigate this in much bigger samples, with more controls, and better data, to understand what that correlation means.”
Bottom line, Dr. Meyerowitz-Katz explained, is that “the link between PFAS and thyroid cancer is, at best, incredibly weak.”
Funding for the study was provided by the National Institutes of Health and The Andrea and Charles Bronfman Philanthropies. One coauthor is cofounder of Linus Biotechnology and is owner of a license agreement with NIES (Japan); received honoraria and travel compensation for lectures for the Bio-Echo and Brin foundations; and has 22 patents at various stages. Dr. Meyerowitz-Katz has no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM EBIOMEDICINE