User login
Hourly air pollution exposure: A risk factor for stroke
TOPLINE:
METHODOLOGY:
- Limited studies have investigated the association between hourly exposure to air pollutants and specific stroke subtypes, especially in regions with moderate to high levels of air pollution.
- The multicenter case-crossover study evaluated the association between hourly exposure to air pollution and stroke among 86,635 emergency admissions for stroke across 10 hospitals in 3 cities.
- Of 86,635 admissions, 79,478 were admitted for ischemic stroke, 3,122 for hemorrhagic stroke, and 4,035 for undetermined type of stroke.
- Hourly levels of fine particulate matter (PM2.5), respirable PM (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected from the China National Environmental Monitoring Center.
TAKEAWAY:
- Exposure to NO2 and SO2 increased the risk for emergency admission for stroke shortly after exposure by 3.34% (95% confidence interval, 1.41%-5.31%) and 2.81% (95% CI, 1.15%-4.51%), respectively.
- Among men, exposure to PM2.5 and PM10 increased the risk for emergency admission for stroke by 3.40% (95% CI, 1.21%-5.64%) and 4.33% (95% CI, 2.18%-6.53%), respectively.
- Among patients aged less than 65 years, exposure to PM10 and NO2 increased the risk for emergency admissions for stroke shortly after exposure by 4.88% (95% CI, 2.29%-7.54%) and 5.59% (95% CI, 2.34%-8.93%), respectively.
IN PRACTICE:
“These variations in susceptibility highlight the importance of implementing effective health protection measures to reduce exposure to air pollution and mitigate the risk of stroke in younger and male populations,” wrote the authors.
SOURCE:
The study was led by Xin Lv, MD, department of epidemiology and biostatistics, School of Public Health, Capital Medical University, Beijing. It was published online in the journal Stroke.
LIMITATIONS:
- Using data from the nearest monitoring site to the hospital address may lead to localized variations in pollution concentrations when assessing exposure.
- There may be a possibility of residual confounding resulting from time-varying lifestyle-related factors.
DISCLOSURES:
This study was supported by the Zhejiang Provincial Project for Medical Research and Health Sciences. No disclosures were reported.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Limited studies have investigated the association between hourly exposure to air pollutants and specific stroke subtypes, especially in regions with moderate to high levels of air pollution.
- The multicenter case-crossover study evaluated the association between hourly exposure to air pollution and stroke among 86,635 emergency admissions for stroke across 10 hospitals in 3 cities.
- Of 86,635 admissions, 79,478 were admitted for ischemic stroke, 3,122 for hemorrhagic stroke, and 4,035 for undetermined type of stroke.
- Hourly levels of fine particulate matter (PM2.5), respirable PM (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected from the China National Environmental Monitoring Center.
TAKEAWAY:
- Exposure to NO2 and SO2 increased the risk for emergency admission for stroke shortly after exposure by 3.34% (95% confidence interval, 1.41%-5.31%) and 2.81% (95% CI, 1.15%-4.51%), respectively.
- Among men, exposure to PM2.5 and PM10 increased the risk for emergency admission for stroke by 3.40% (95% CI, 1.21%-5.64%) and 4.33% (95% CI, 2.18%-6.53%), respectively.
- Among patients aged less than 65 years, exposure to PM10 and NO2 increased the risk for emergency admissions for stroke shortly after exposure by 4.88% (95% CI, 2.29%-7.54%) and 5.59% (95% CI, 2.34%-8.93%), respectively.
IN PRACTICE:
“These variations in susceptibility highlight the importance of implementing effective health protection measures to reduce exposure to air pollution and mitigate the risk of stroke in younger and male populations,” wrote the authors.
SOURCE:
The study was led by Xin Lv, MD, department of epidemiology and biostatistics, School of Public Health, Capital Medical University, Beijing. It was published online in the journal Stroke.
LIMITATIONS:
- Using data from the nearest monitoring site to the hospital address may lead to localized variations in pollution concentrations when assessing exposure.
- There may be a possibility of residual confounding resulting from time-varying lifestyle-related factors.
DISCLOSURES:
This study was supported by the Zhejiang Provincial Project for Medical Research and Health Sciences. No disclosures were reported.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Limited studies have investigated the association between hourly exposure to air pollutants and specific stroke subtypes, especially in regions with moderate to high levels of air pollution.
- The multicenter case-crossover study evaluated the association between hourly exposure to air pollution and stroke among 86,635 emergency admissions for stroke across 10 hospitals in 3 cities.
- Of 86,635 admissions, 79,478 were admitted for ischemic stroke, 3,122 for hemorrhagic stroke, and 4,035 for undetermined type of stroke.
- Hourly levels of fine particulate matter (PM2.5), respirable PM (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected from the China National Environmental Monitoring Center.
TAKEAWAY:
- Exposure to NO2 and SO2 increased the risk for emergency admission for stroke shortly after exposure by 3.34% (95% confidence interval, 1.41%-5.31%) and 2.81% (95% CI, 1.15%-4.51%), respectively.
- Among men, exposure to PM2.5 and PM10 increased the risk for emergency admission for stroke by 3.40% (95% CI, 1.21%-5.64%) and 4.33% (95% CI, 2.18%-6.53%), respectively.
- Among patients aged less than 65 years, exposure to PM10 and NO2 increased the risk for emergency admissions for stroke shortly after exposure by 4.88% (95% CI, 2.29%-7.54%) and 5.59% (95% CI, 2.34%-8.93%), respectively.
IN PRACTICE:
“These variations in susceptibility highlight the importance of implementing effective health protection measures to reduce exposure to air pollution and mitigate the risk of stroke in younger and male populations,” wrote the authors.
SOURCE:
The study was led by Xin Lv, MD, department of epidemiology and biostatistics, School of Public Health, Capital Medical University, Beijing. It was published online in the journal Stroke.
LIMITATIONS:
- Using data from the nearest monitoring site to the hospital address may lead to localized variations in pollution concentrations when assessing exposure.
- There may be a possibility of residual confounding resulting from time-varying lifestyle-related factors.
DISCLOSURES:
This study was supported by the Zhejiang Provincial Project for Medical Research and Health Sciences. No disclosures were reported.
A version of this article first appeared on Medscape.com.
Spinal cord stimulator restores Parkinson patient’s gait
The neuroprosthesis involves targeted epidural electrical stimulation of areas of the lumbosacral spinal cord that produce walking.
This new therapeutic tool offers hope to patients with PD and, combined with existing approaches, may alleviate a motor sign in PD for which there is currently “no real solution,” study investigator Eduardo Martin Moraud, PhD, who leads PD research at the Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland, said in an interview.
“This is exciting for the many patients that develop gait deficits and experience frequent falls, who can only rely on physical therapy to try and minimize the consequences,” he added.
The findings were published online in Nature Medicine.
Personalized stimulation
About 90% of people with advanced PD experience gait and balance problems or freezing-of-gait episodes. These locomotor deficits typically don’t respond well to dopamine replacement therapy or deep brain stimulation (DBS) of the subthalamic nucleus, possibly because the neural origins of these motor problems involve brain circuits not related to dopamine, said Dr. Moraud.
Continuous electrical stimulation over the cervical or thoracic segments of the spinal cord reduces locomotor deficits in some people with PD, but the broader application of this strategy has led to variable and unsatisfying outcomes.
The new approach focuses on correcting abnormal activation of circuits in the lumbar spinal cord, a region that hosts all the neurons that control activation of the leg muscles used for walking.
The stimulating device is placed on the lumbar region of the spinal cord, which sends messages to leg muscles. It is wired to a small impulse generator implanted under the skin of the abdomen. Sensors placed in shoes align the stimulation to the patient’s movement.
The system can detect the beginning of a movement, immediately activate the appropriate electrode, and so facilitate the necessary movement, be that leg flexion, extension, or propulsion, said Dr. Moraud. “This allows for increased walking symmetry, reinforced balance, and increased length of steps.”
The concept of this neuroprosthesis is similar to that used to allow patients with a spinal cord injury (SCI) to walk. But unlike patients with SCI, those with PD can move their legs, indicating that there is a descending command from the brain that needs to interact with the stimulation of the spinal cord, and patients with PD can feel the stimulation.
“Both these elements imply that amplitudes of stimulation need to be much lower in PD than SCI, and that stimulation needs to be fully personalized in PD to synergistically interact with the descending commands from the brain.”
After fine-tuning this new neuroprosthesis in animal models, researchers implanted the device in a 62-year-old man with a 30-year history of PD who presented with severe gait impairments, including marked gait asymmetry, reduced stride length, and balance problems.
Gait restored to near normal
The patient had frequent freezing-of-gait episodes when turning and passing through narrow paths, which led to multiple falls a day. This was despite being treated with DBS and dopaminergic replacement therapies.
But after getting used to the neuroprosthesis, the patient now walks with a gait akin to that of people without PD.
“Our experience in the preclinical animal models and this first patient is that gait can be restored to an almost healthy level, but this, of course, may vary across patients, depending on the severity of their disease progression, and their other motor deficits,” said Dr. Moraud.
When the neuroprosthesis is turned on, freezing of gait nearly vanishes, both with and without DBS.
In addition, the neuroprosthesis augmented the impact of the patient’s rehabilitation program, which involved a variety of regular exercises, including walking on basic and complex terrains, navigating outdoors in community settings, balance training, and basic physical therapy.
Frequent use of the neuroprosthesis during gait rehabilitation also translated into “highly improved” quality of life as reported by the patient (and his wife), said Dr. Moraud.
The patient has now been using the neuroprosthesis about 8 hours a day for nearly 2 years, only switching it off when sitting for long periods of time or while sleeping.
“He regained the capacity to walk in complex or crowded environments such as shops, airports, or his own home, without falling,” said Dr. Moraud. “He went from falling five to six times per day to one or two [falls] every couple of weeks. He’s also much more confident. He can walk for many miles, run, and go on holidays, without the constant fear of falling and having related injuries.”
Dr. Moraud stressed that the device does not replace DBS, which is a “key therapy” that addresses other deficits in PD, such as rigidity or slowness of movement. “What we propose here is a fully complementary approach for the gait problems that are not well addressed by DBS.”
One of the next steps will be to evaluate the efficacy of this approach across a wider spectrum of patient profiles to fully define the best responders, said Dr. Moraud.
A ‘tour de force’
In a comment, Michael S. Okun, MD, director of the Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, and medical director of the Parkinson’s Foundation, noted that the researchers used “a smarter device” than past approaches that failed to adequately address progressive walking challenges of patients with PD.
Although it’s “tempting to get excited” about the findings, it’s important to consider that the study included only one human subject and did not target circuits for both walking and balance, said Dr. Okun. “It’s possible that even if future studies revealed a benefit for walking, the device may or may not address falling.”
In an accompanying editorial, Aviv Mizrahi-Kliger, MD, PhD, department of neurology, University of California, San Francisco, and Karunesh Ganguly, MD, PhD, Neurology and Rehabilitation Service, San Francisco Veterans Affairs Health Care System, called the study an “impressive tour de force,” with data from the nonhuman primate model and the individual with PD “jointly” indicating that epidural electrical stimulation (EES) “is a very promising treatment for several aspects of gait, posture and balance impairments in PD.”
But although the effect in the single patient “is quite impressive,” the “next crucial step” is to test this approach in a larger cohort of patients, they said.
They noted the nonhuman model does not exhibit freezing of gait, “which precluded the ability to corroborate or further study the role of EES in alleviating this symptom of PD in an animal model.”
In addition, stimulation parameters in the patient with PD “had to rely on estimated normal activity patterns, owing to the inability to measure pre-disease patterns at the individual level,” they wrote.
The study received funding from the Defitech Foundation, ONWARD Medical, CAMS Innovation Fund for Medical Sciences, National Natural Science Foundation of China, Parkinson Schweiz Foundation, European Community’s Seventh Framework Program (NeuWalk), European Research Council, Wyss Center for Bio and Neuroengineering, Bertarelli Foundation, and Swiss National Science Foundation. Dr. Moraud and other study authors hold various patents or applications in relation to the present work. Dr. Mizrahi-Kliger has no relevant conflicts of interest; Dr. Ganguly has a patent for modulation of sensory inputs to improve motor recovery from stroke and has been a consultant to Cala Health.
A version of this article first appeared on Medscape.com.
The neuroprosthesis involves targeted epidural electrical stimulation of areas of the lumbosacral spinal cord that produce walking.
This new therapeutic tool offers hope to patients with PD and, combined with existing approaches, may alleviate a motor sign in PD for which there is currently “no real solution,” study investigator Eduardo Martin Moraud, PhD, who leads PD research at the Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland, said in an interview.
“This is exciting for the many patients that develop gait deficits and experience frequent falls, who can only rely on physical therapy to try and minimize the consequences,” he added.
The findings were published online in Nature Medicine.
Personalized stimulation
About 90% of people with advanced PD experience gait and balance problems or freezing-of-gait episodes. These locomotor deficits typically don’t respond well to dopamine replacement therapy or deep brain stimulation (DBS) of the subthalamic nucleus, possibly because the neural origins of these motor problems involve brain circuits not related to dopamine, said Dr. Moraud.
Continuous electrical stimulation over the cervical or thoracic segments of the spinal cord reduces locomotor deficits in some people with PD, but the broader application of this strategy has led to variable and unsatisfying outcomes.
The new approach focuses on correcting abnormal activation of circuits in the lumbar spinal cord, a region that hosts all the neurons that control activation of the leg muscles used for walking.
The stimulating device is placed on the lumbar region of the spinal cord, which sends messages to leg muscles. It is wired to a small impulse generator implanted under the skin of the abdomen. Sensors placed in shoes align the stimulation to the patient’s movement.
The system can detect the beginning of a movement, immediately activate the appropriate electrode, and so facilitate the necessary movement, be that leg flexion, extension, or propulsion, said Dr. Moraud. “This allows for increased walking symmetry, reinforced balance, and increased length of steps.”
The concept of this neuroprosthesis is similar to that used to allow patients with a spinal cord injury (SCI) to walk. But unlike patients with SCI, those with PD can move their legs, indicating that there is a descending command from the brain that needs to interact with the stimulation of the spinal cord, and patients with PD can feel the stimulation.
“Both these elements imply that amplitudes of stimulation need to be much lower in PD than SCI, and that stimulation needs to be fully personalized in PD to synergistically interact with the descending commands from the brain.”
After fine-tuning this new neuroprosthesis in animal models, researchers implanted the device in a 62-year-old man with a 30-year history of PD who presented with severe gait impairments, including marked gait asymmetry, reduced stride length, and balance problems.
Gait restored to near normal
The patient had frequent freezing-of-gait episodes when turning and passing through narrow paths, which led to multiple falls a day. This was despite being treated with DBS and dopaminergic replacement therapies.
But after getting used to the neuroprosthesis, the patient now walks with a gait akin to that of people without PD.
“Our experience in the preclinical animal models and this first patient is that gait can be restored to an almost healthy level, but this, of course, may vary across patients, depending on the severity of their disease progression, and their other motor deficits,” said Dr. Moraud.
When the neuroprosthesis is turned on, freezing of gait nearly vanishes, both with and without DBS.
In addition, the neuroprosthesis augmented the impact of the patient’s rehabilitation program, which involved a variety of regular exercises, including walking on basic and complex terrains, navigating outdoors in community settings, balance training, and basic physical therapy.
Frequent use of the neuroprosthesis during gait rehabilitation also translated into “highly improved” quality of life as reported by the patient (and his wife), said Dr. Moraud.
The patient has now been using the neuroprosthesis about 8 hours a day for nearly 2 years, only switching it off when sitting for long periods of time or while sleeping.
“He regained the capacity to walk in complex or crowded environments such as shops, airports, or his own home, without falling,” said Dr. Moraud. “He went from falling five to six times per day to one or two [falls] every couple of weeks. He’s also much more confident. He can walk for many miles, run, and go on holidays, without the constant fear of falling and having related injuries.”
Dr. Moraud stressed that the device does not replace DBS, which is a “key therapy” that addresses other deficits in PD, such as rigidity or slowness of movement. “What we propose here is a fully complementary approach for the gait problems that are not well addressed by DBS.”
One of the next steps will be to evaluate the efficacy of this approach across a wider spectrum of patient profiles to fully define the best responders, said Dr. Moraud.
A ‘tour de force’
In a comment, Michael S. Okun, MD, director of the Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, and medical director of the Parkinson’s Foundation, noted that the researchers used “a smarter device” than past approaches that failed to adequately address progressive walking challenges of patients with PD.
Although it’s “tempting to get excited” about the findings, it’s important to consider that the study included only one human subject and did not target circuits for both walking and balance, said Dr. Okun. “It’s possible that even if future studies revealed a benefit for walking, the device may or may not address falling.”
In an accompanying editorial, Aviv Mizrahi-Kliger, MD, PhD, department of neurology, University of California, San Francisco, and Karunesh Ganguly, MD, PhD, Neurology and Rehabilitation Service, San Francisco Veterans Affairs Health Care System, called the study an “impressive tour de force,” with data from the nonhuman primate model and the individual with PD “jointly” indicating that epidural electrical stimulation (EES) “is a very promising treatment for several aspects of gait, posture and balance impairments in PD.”
But although the effect in the single patient “is quite impressive,” the “next crucial step” is to test this approach in a larger cohort of patients, they said.
They noted the nonhuman model does not exhibit freezing of gait, “which precluded the ability to corroborate or further study the role of EES in alleviating this symptom of PD in an animal model.”
In addition, stimulation parameters in the patient with PD “had to rely on estimated normal activity patterns, owing to the inability to measure pre-disease patterns at the individual level,” they wrote.
The study received funding from the Defitech Foundation, ONWARD Medical, CAMS Innovation Fund for Medical Sciences, National Natural Science Foundation of China, Parkinson Schweiz Foundation, European Community’s Seventh Framework Program (NeuWalk), European Research Council, Wyss Center for Bio and Neuroengineering, Bertarelli Foundation, and Swiss National Science Foundation. Dr. Moraud and other study authors hold various patents or applications in relation to the present work. Dr. Mizrahi-Kliger has no relevant conflicts of interest; Dr. Ganguly has a patent for modulation of sensory inputs to improve motor recovery from stroke and has been a consultant to Cala Health.
A version of this article first appeared on Medscape.com.
The neuroprosthesis involves targeted epidural electrical stimulation of areas of the lumbosacral spinal cord that produce walking.
This new therapeutic tool offers hope to patients with PD and, combined with existing approaches, may alleviate a motor sign in PD for which there is currently “no real solution,” study investigator Eduardo Martin Moraud, PhD, who leads PD research at the Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland, said in an interview.
“This is exciting for the many patients that develop gait deficits and experience frequent falls, who can only rely on physical therapy to try and minimize the consequences,” he added.
The findings were published online in Nature Medicine.
Personalized stimulation
About 90% of people with advanced PD experience gait and balance problems or freezing-of-gait episodes. These locomotor deficits typically don’t respond well to dopamine replacement therapy or deep brain stimulation (DBS) of the subthalamic nucleus, possibly because the neural origins of these motor problems involve brain circuits not related to dopamine, said Dr. Moraud.
Continuous electrical stimulation over the cervical or thoracic segments of the spinal cord reduces locomotor deficits in some people with PD, but the broader application of this strategy has led to variable and unsatisfying outcomes.
The new approach focuses on correcting abnormal activation of circuits in the lumbar spinal cord, a region that hosts all the neurons that control activation of the leg muscles used for walking.
The stimulating device is placed on the lumbar region of the spinal cord, which sends messages to leg muscles. It is wired to a small impulse generator implanted under the skin of the abdomen. Sensors placed in shoes align the stimulation to the patient’s movement.
The system can detect the beginning of a movement, immediately activate the appropriate electrode, and so facilitate the necessary movement, be that leg flexion, extension, or propulsion, said Dr. Moraud. “This allows for increased walking symmetry, reinforced balance, and increased length of steps.”
The concept of this neuroprosthesis is similar to that used to allow patients with a spinal cord injury (SCI) to walk. But unlike patients with SCI, those with PD can move their legs, indicating that there is a descending command from the brain that needs to interact with the stimulation of the spinal cord, and patients with PD can feel the stimulation.
“Both these elements imply that amplitudes of stimulation need to be much lower in PD than SCI, and that stimulation needs to be fully personalized in PD to synergistically interact with the descending commands from the brain.”
After fine-tuning this new neuroprosthesis in animal models, researchers implanted the device in a 62-year-old man with a 30-year history of PD who presented with severe gait impairments, including marked gait asymmetry, reduced stride length, and balance problems.
Gait restored to near normal
The patient had frequent freezing-of-gait episodes when turning and passing through narrow paths, which led to multiple falls a day. This was despite being treated with DBS and dopaminergic replacement therapies.
But after getting used to the neuroprosthesis, the patient now walks with a gait akin to that of people without PD.
“Our experience in the preclinical animal models and this first patient is that gait can be restored to an almost healthy level, but this, of course, may vary across patients, depending on the severity of their disease progression, and their other motor deficits,” said Dr. Moraud.
When the neuroprosthesis is turned on, freezing of gait nearly vanishes, both with and without DBS.
In addition, the neuroprosthesis augmented the impact of the patient’s rehabilitation program, which involved a variety of regular exercises, including walking on basic and complex terrains, navigating outdoors in community settings, balance training, and basic physical therapy.
Frequent use of the neuroprosthesis during gait rehabilitation also translated into “highly improved” quality of life as reported by the patient (and his wife), said Dr. Moraud.
The patient has now been using the neuroprosthesis about 8 hours a day for nearly 2 years, only switching it off when sitting for long periods of time or while sleeping.
“He regained the capacity to walk in complex or crowded environments such as shops, airports, or his own home, without falling,” said Dr. Moraud. “He went from falling five to six times per day to one or two [falls] every couple of weeks. He’s also much more confident. He can walk for many miles, run, and go on holidays, without the constant fear of falling and having related injuries.”
Dr. Moraud stressed that the device does not replace DBS, which is a “key therapy” that addresses other deficits in PD, such as rigidity or slowness of movement. “What we propose here is a fully complementary approach for the gait problems that are not well addressed by DBS.”
One of the next steps will be to evaluate the efficacy of this approach across a wider spectrum of patient profiles to fully define the best responders, said Dr. Moraud.
A ‘tour de force’
In a comment, Michael S. Okun, MD, director of the Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, and medical director of the Parkinson’s Foundation, noted that the researchers used “a smarter device” than past approaches that failed to adequately address progressive walking challenges of patients with PD.
Although it’s “tempting to get excited” about the findings, it’s important to consider that the study included only one human subject and did not target circuits for both walking and balance, said Dr. Okun. “It’s possible that even if future studies revealed a benefit for walking, the device may or may not address falling.”
In an accompanying editorial, Aviv Mizrahi-Kliger, MD, PhD, department of neurology, University of California, San Francisco, and Karunesh Ganguly, MD, PhD, Neurology and Rehabilitation Service, San Francisco Veterans Affairs Health Care System, called the study an “impressive tour de force,” with data from the nonhuman primate model and the individual with PD “jointly” indicating that epidural electrical stimulation (EES) “is a very promising treatment for several aspects of gait, posture and balance impairments in PD.”
But although the effect in the single patient “is quite impressive,” the “next crucial step” is to test this approach in a larger cohort of patients, they said.
They noted the nonhuman model does not exhibit freezing of gait, “which precluded the ability to corroborate or further study the role of EES in alleviating this symptom of PD in an animal model.”
In addition, stimulation parameters in the patient with PD “had to rely on estimated normal activity patterns, owing to the inability to measure pre-disease patterns at the individual level,” they wrote.
The study received funding from the Defitech Foundation, ONWARD Medical, CAMS Innovation Fund for Medical Sciences, National Natural Science Foundation of China, Parkinson Schweiz Foundation, European Community’s Seventh Framework Program (NeuWalk), European Research Council, Wyss Center for Bio and Neuroengineering, Bertarelli Foundation, and Swiss National Science Foundation. Dr. Moraud and other study authors hold various patents or applications in relation to the present work. Dr. Mizrahi-Kliger has no relevant conflicts of interest; Dr. Ganguly has a patent for modulation of sensory inputs to improve motor recovery from stroke and has been a consultant to Cala Health.
A version of this article first appeared on Medscape.com.
FROM NATURE MEDICINE
People with diabetes have a higher risk of colon cancer: Study
Getting a colonoscopy dramatically reduced the risk, the results showed.
The findings, published in JAMA Network Open, suggest that colonoscopies are particularly important for people with diabetes. People diagnosed with diabetes within the past 5 years have the greatest colorectal cancer risk, the study found, suggesting screening should be part of a person’s health care after they’re diagnosed with diabetes.
Researchers analyzed data for 54,597 people who contributed at least 2 years of health data as part of a study that recruited people from 12 Southeastern states between 2002 and 2009. The people self-reported their diabetes status, and although researchers tried to only include people with type 2 diabetes, it’s possible that some people in the study had type 1 diabetes. The average age of those in the study was 51 years old; 64% were women; more than half of them had an income of less than $15,000 per year; and 66% of them were African American.
Among the people in the study who had diabetes, the risk of having colorectal cancer was not strongly impacted by their race or ethnicity, gender, weight, or income level, the study showed.
While race didn’t predict whether people with diabetes would get colorectal cancer, the findings are particularly important because most of the people in the study were African American. Diabetes and colorectal cancer disproportionately affect African American people, the authors noted. Medical research studies often struggle to recruit people of color, resulting in a lack of data to help guide health care priorities and decision-making.
The study also provided important guidance for people newly diagnosed with diabetes. People who were diagnosed with diabetes within the past 5 years were at a particularly increased risk of getting colorectal cancer, compared to people who had been diagnosed for 5-10 years.
The authors concluded that increased referrals for colonoscopies among people with diabetes, particularly among those newly diagnosed, could greatly reduce the impact of colorectal cancer. Current guidelines suggest most people should begin colorectal cancer screenings at age 45, according to the Centers for Disease Control and Prevention.
The study was supported by the National Cancer Institute and the University of Wisconsin, Madison. The study authors reported no relevant conflicts of interest.
A version of this article first appeared on WebMD.com.
Getting a colonoscopy dramatically reduced the risk, the results showed.
The findings, published in JAMA Network Open, suggest that colonoscopies are particularly important for people with diabetes. People diagnosed with diabetes within the past 5 years have the greatest colorectal cancer risk, the study found, suggesting screening should be part of a person’s health care after they’re diagnosed with diabetes.
Researchers analyzed data for 54,597 people who contributed at least 2 years of health data as part of a study that recruited people from 12 Southeastern states between 2002 and 2009. The people self-reported their diabetes status, and although researchers tried to only include people with type 2 diabetes, it’s possible that some people in the study had type 1 diabetes. The average age of those in the study was 51 years old; 64% were women; more than half of them had an income of less than $15,000 per year; and 66% of them were African American.
Among the people in the study who had diabetes, the risk of having colorectal cancer was not strongly impacted by their race or ethnicity, gender, weight, or income level, the study showed.
While race didn’t predict whether people with diabetes would get colorectal cancer, the findings are particularly important because most of the people in the study were African American. Diabetes and colorectal cancer disproportionately affect African American people, the authors noted. Medical research studies often struggle to recruit people of color, resulting in a lack of data to help guide health care priorities and decision-making.
The study also provided important guidance for people newly diagnosed with diabetes. People who were diagnosed with diabetes within the past 5 years were at a particularly increased risk of getting colorectal cancer, compared to people who had been diagnosed for 5-10 years.
The authors concluded that increased referrals for colonoscopies among people with diabetes, particularly among those newly diagnosed, could greatly reduce the impact of colorectal cancer. Current guidelines suggest most people should begin colorectal cancer screenings at age 45, according to the Centers for Disease Control and Prevention.
The study was supported by the National Cancer Institute and the University of Wisconsin, Madison. The study authors reported no relevant conflicts of interest.
A version of this article first appeared on WebMD.com.
Getting a colonoscopy dramatically reduced the risk, the results showed.
The findings, published in JAMA Network Open, suggest that colonoscopies are particularly important for people with diabetes. People diagnosed with diabetes within the past 5 years have the greatest colorectal cancer risk, the study found, suggesting screening should be part of a person’s health care after they’re diagnosed with diabetes.
Researchers analyzed data for 54,597 people who contributed at least 2 years of health data as part of a study that recruited people from 12 Southeastern states between 2002 and 2009. The people self-reported their diabetes status, and although researchers tried to only include people with type 2 diabetes, it’s possible that some people in the study had type 1 diabetes. The average age of those in the study was 51 years old; 64% were women; more than half of them had an income of less than $15,000 per year; and 66% of them were African American.
Among the people in the study who had diabetes, the risk of having colorectal cancer was not strongly impacted by their race or ethnicity, gender, weight, or income level, the study showed.
While race didn’t predict whether people with diabetes would get colorectal cancer, the findings are particularly important because most of the people in the study were African American. Diabetes and colorectal cancer disproportionately affect African American people, the authors noted. Medical research studies often struggle to recruit people of color, resulting in a lack of data to help guide health care priorities and decision-making.
The study also provided important guidance for people newly diagnosed with diabetes. People who were diagnosed with diabetes within the past 5 years were at a particularly increased risk of getting colorectal cancer, compared to people who had been diagnosed for 5-10 years.
The authors concluded that increased referrals for colonoscopies among people with diabetes, particularly among those newly diagnosed, could greatly reduce the impact of colorectal cancer. Current guidelines suggest most people should begin colorectal cancer screenings at age 45, according to the Centers for Disease Control and Prevention.
The study was supported by the National Cancer Institute and the University of Wisconsin, Madison. The study authors reported no relevant conflicts of interest.
A version of this article first appeared on WebMD.com.
FROM JAMA NETWORK OPEN
Blood test could predict future disability in MS
a new study suggests.
Rising NfL levels are a known indicator of neuroaxonal injury and correlate with MS disease activity. Levels rise in the presence of an MS relapse or MRI activity and fall following treatment with disease-modifying therapies. But the link between NfL levels and worsening disability was less understood.
This new analysis of NfL in two large MS cohorts found that elevated levels of the neuronal protein at baseline were associated with large increases in future disability risk, even in patients with no clinical relapse.
“This rising of NfL up to 2 years before signs of disability worsening represents the window when interventions may prevent worsening,” lead investigator Ahmed Abdelhak, MD, department of neurology, University of California, San Francisco, said in a press release.
The findings were published online in JAMA Neurology.
Early warning system?
The study included data on 1,899 patients with nearly 13,000 patient visits from two observational, long-term, real-world cohorts: the U.S.-based Expression, Proteomics, Imaging, Clinical (EPIC) study (n = 609 patients), and the Swiss Multiple Sclerosis Cohort trial (SMSC; n = 1,290 patients).
Investigators analyzed longitudinal serum NfL measurements in conjunction with clinical disability worsening, defined as 6 months or more of increased impairment as measured by the Expanded Disability Status Scale.
Researchers also assessed the temporal association between NfL measurements and the risk of increased disability and distinguished between disability with and without relapse.
Worsening disability was reported in 227 patients in the EPIC group and 435 in the SMSC trial.
Elevated NfL at baseline was associated with a 70% higher risk for worsening disability with relapse about 11 months later in the SMSC study (hazard ratio, 1.70; P = .02). In the EPIC trial, there was trend toward a 91% higher risk for worsening disability with relapse at 12.6 months, although the findings did not meet statistical significance (HR, 1.91; P = .07).
The risk of future disability progression independent of clinical relapse was 40% higher in those with high NfL at baseline in the EPIC study 12 months after baseline (HR, 1.40; P = .02) and 49% higher in the SMSC trial 21 months later (HR, 1.49; P < .001).
The early elevation of NfL levels suggests a slower degradation of nerve cells and could be a possible early warning system of future progression of disability, allowing time for interventions that could slow or even halt further disability.
“Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging,” senior author Jens Kuhle, MD, PhD, leader of the Swiss cohort and head of the Multiple Sclerosis Center at University Hospital and University of Basel, said in a statement.
Challenges for clinicians
Commenting on the findings, Robert Fox, MD, staff neurologist at the Mellen Center for MS and vice chair for research, Neurological Institute, Cleveland Clinic, said that, while there is a clinical test to measure NfL levels, incorporating that test into standard of care isn’t straightforward.
“The challenge for the practicing clinician is to translate these population-level studies to individual patient management decisions,” said Dr. Fox, who was not a part of the study.
“The published prediction curves corrected for age, sex, disease course, disease-modifying treatment, relapse within the past 90 days, and current disability status, the combination of which makes it rather challenging to calculate and interpret adjusted z score NfL levels in routine practice and then use it in clinical decision-making.”
The investigators said the study underscores the importance of NfL as an MS biomarker and “points to the existence of different windows of dynamic central nervous system pathology” that precedes worsening disability with or without relapse. But there may be a simpler explanation, Dr. Fox suggested.
“We know MRI activity occurs 5-10 times more frequently than relapses, and we know that MRI activity is associated with both NfL increases and future disability progression,” Dr. Fox said. “It is quite likely that the elevations in NfL seen here are reflective of new MRI disease activity, which frequently is seen without symptoms of an MS relapse,” he said
The study was funded by the Westridge Foundation, F. Hoffmann–La Roche, the Fishman Family, the Swiss National Research Foundation, the National Institutes of Health/National Institute of Neurological Disorders and Stroke, and the Valhalla Foundation. Dr. Abdelhak reported receiving grants from the German Multiple Sclerosis Society and the Weill Institute for Neurosciences outside the submitted work. Dr. Kuhle has received grants from Swiss MS Society, the Swiss National Research Foundation, the Progressive MS Alliance, Biogen, Merck, Celgene, Bristol-Myers Squibb, Novartis, Octave Bioscience, Roche, Sanofi, Alnylam, Bayer, Immunic, Quanterix, Neurogenesis, Stata DX, and the University of Basel outside the submitted work. Dr. Fox reported receiving consulting fees from Siemens and Roche.
A version of this article appeared on Medscape.com.
a new study suggests.
Rising NfL levels are a known indicator of neuroaxonal injury and correlate with MS disease activity. Levels rise in the presence of an MS relapse or MRI activity and fall following treatment with disease-modifying therapies. But the link between NfL levels and worsening disability was less understood.
This new analysis of NfL in two large MS cohorts found that elevated levels of the neuronal protein at baseline were associated with large increases in future disability risk, even in patients with no clinical relapse.
“This rising of NfL up to 2 years before signs of disability worsening represents the window when interventions may prevent worsening,” lead investigator Ahmed Abdelhak, MD, department of neurology, University of California, San Francisco, said in a press release.
The findings were published online in JAMA Neurology.
Early warning system?
The study included data on 1,899 patients with nearly 13,000 patient visits from two observational, long-term, real-world cohorts: the U.S.-based Expression, Proteomics, Imaging, Clinical (EPIC) study (n = 609 patients), and the Swiss Multiple Sclerosis Cohort trial (SMSC; n = 1,290 patients).
Investigators analyzed longitudinal serum NfL measurements in conjunction with clinical disability worsening, defined as 6 months or more of increased impairment as measured by the Expanded Disability Status Scale.
Researchers also assessed the temporal association between NfL measurements and the risk of increased disability and distinguished between disability with and without relapse.
Worsening disability was reported in 227 patients in the EPIC group and 435 in the SMSC trial.
Elevated NfL at baseline was associated with a 70% higher risk for worsening disability with relapse about 11 months later in the SMSC study (hazard ratio, 1.70; P = .02). In the EPIC trial, there was trend toward a 91% higher risk for worsening disability with relapse at 12.6 months, although the findings did not meet statistical significance (HR, 1.91; P = .07).
The risk of future disability progression independent of clinical relapse was 40% higher in those with high NfL at baseline in the EPIC study 12 months after baseline (HR, 1.40; P = .02) and 49% higher in the SMSC trial 21 months later (HR, 1.49; P < .001).
The early elevation of NfL levels suggests a slower degradation of nerve cells and could be a possible early warning system of future progression of disability, allowing time for interventions that could slow or even halt further disability.
“Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging,” senior author Jens Kuhle, MD, PhD, leader of the Swiss cohort and head of the Multiple Sclerosis Center at University Hospital and University of Basel, said in a statement.
Challenges for clinicians
Commenting on the findings, Robert Fox, MD, staff neurologist at the Mellen Center for MS and vice chair for research, Neurological Institute, Cleveland Clinic, said that, while there is a clinical test to measure NfL levels, incorporating that test into standard of care isn’t straightforward.
“The challenge for the practicing clinician is to translate these population-level studies to individual patient management decisions,” said Dr. Fox, who was not a part of the study.
“The published prediction curves corrected for age, sex, disease course, disease-modifying treatment, relapse within the past 90 days, and current disability status, the combination of which makes it rather challenging to calculate and interpret adjusted z score NfL levels in routine practice and then use it in clinical decision-making.”
The investigators said the study underscores the importance of NfL as an MS biomarker and “points to the existence of different windows of dynamic central nervous system pathology” that precedes worsening disability with or without relapse. But there may be a simpler explanation, Dr. Fox suggested.
“We know MRI activity occurs 5-10 times more frequently than relapses, and we know that MRI activity is associated with both NfL increases and future disability progression,” Dr. Fox said. “It is quite likely that the elevations in NfL seen here are reflective of new MRI disease activity, which frequently is seen without symptoms of an MS relapse,” he said
The study was funded by the Westridge Foundation, F. Hoffmann–La Roche, the Fishman Family, the Swiss National Research Foundation, the National Institutes of Health/National Institute of Neurological Disorders and Stroke, and the Valhalla Foundation. Dr. Abdelhak reported receiving grants from the German Multiple Sclerosis Society and the Weill Institute for Neurosciences outside the submitted work. Dr. Kuhle has received grants from Swiss MS Society, the Swiss National Research Foundation, the Progressive MS Alliance, Biogen, Merck, Celgene, Bristol-Myers Squibb, Novartis, Octave Bioscience, Roche, Sanofi, Alnylam, Bayer, Immunic, Quanterix, Neurogenesis, Stata DX, and the University of Basel outside the submitted work. Dr. Fox reported receiving consulting fees from Siemens and Roche.
A version of this article appeared on Medscape.com.
a new study suggests.
Rising NfL levels are a known indicator of neuroaxonal injury and correlate with MS disease activity. Levels rise in the presence of an MS relapse or MRI activity and fall following treatment with disease-modifying therapies. But the link between NfL levels and worsening disability was less understood.
This new analysis of NfL in two large MS cohorts found that elevated levels of the neuronal protein at baseline were associated with large increases in future disability risk, even in patients with no clinical relapse.
“This rising of NfL up to 2 years before signs of disability worsening represents the window when interventions may prevent worsening,” lead investigator Ahmed Abdelhak, MD, department of neurology, University of California, San Francisco, said in a press release.
The findings were published online in JAMA Neurology.
Early warning system?
The study included data on 1,899 patients with nearly 13,000 patient visits from two observational, long-term, real-world cohorts: the U.S.-based Expression, Proteomics, Imaging, Clinical (EPIC) study (n = 609 patients), and the Swiss Multiple Sclerosis Cohort trial (SMSC; n = 1,290 patients).
Investigators analyzed longitudinal serum NfL measurements in conjunction with clinical disability worsening, defined as 6 months or more of increased impairment as measured by the Expanded Disability Status Scale.
Researchers also assessed the temporal association between NfL measurements and the risk of increased disability and distinguished between disability with and without relapse.
Worsening disability was reported in 227 patients in the EPIC group and 435 in the SMSC trial.
Elevated NfL at baseline was associated with a 70% higher risk for worsening disability with relapse about 11 months later in the SMSC study (hazard ratio, 1.70; P = .02). In the EPIC trial, there was trend toward a 91% higher risk for worsening disability with relapse at 12.6 months, although the findings did not meet statistical significance (HR, 1.91; P = .07).
The risk of future disability progression independent of clinical relapse was 40% higher in those with high NfL at baseline in the EPIC study 12 months after baseline (HR, 1.40; P = .02) and 49% higher in the SMSC trial 21 months later (HR, 1.49; P < .001).
The early elevation of NfL levels suggests a slower degradation of nerve cells and could be a possible early warning system of future progression of disability, allowing time for interventions that could slow or even halt further disability.
“Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging,” senior author Jens Kuhle, MD, PhD, leader of the Swiss cohort and head of the Multiple Sclerosis Center at University Hospital and University of Basel, said in a statement.
Challenges for clinicians
Commenting on the findings, Robert Fox, MD, staff neurologist at the Mellen Center for MS and vice chair for research, Neurological Institute, Cleveland Clinic, said that, while there is a clinical test to measure NfL levels, incorporating that test into standard of care isn’t straightforward.
“The challenge for the practicing clinician is to translate these population-level studies to individual patient management decisions,” said Dr. Fox, who was not a part of the study.
“The published prediction curves corrected for age, sex, disease course, disease-modifying treatment, relapse within the past 90 days, and current disability status, the combination of which makes it rather challenging to calculate and interpret adjusted z score NfL levels in routine practice and then use it in clinical decision-making.”
The investigators said the study underscores the importance of NfL as an MS biomarker and “points to the existence of different windows of dynamic central nervous system pathology” that precedes worsening disability with or without relapse. But there may be a simpler explanation, Dr. Fox suggested.
“We know MRI activity occurs 5-10 times more frequently than relapses, and we know that MRI activity is associated with both NfL increases and future disability progression,” Dr. Fox said. “It is quite likely that the elevations in NfL seen here are reflective of new MRI disease activity, which frequently is seen without symptoms of an MS relapse,” he said
The study was funded by the Westridge Foundation, F. Hoffmann–La Roche, the Fishman Family, the Swiss National Research Foundation, the National Institutes of Health/National Institute of Neurological Disorders and Stroke, and the Valhalla Foundation. Dr. Abdelhak reported receiving grants from the German Multiple Sclerosis Society and the Weill Institute for Neurosciences outside the submitted work. Dr. Kuhle has received grants from Swiss MS Society, the Swiss National Research Foundation, the Progressive MS Alliance, Biogen, Merck, Celgene, Bristol-Myers Squibb, Novartis, Octave Bioscience, Roche, Sanofi, Alnylam, Bayer, Immunic, Quanterix, Neurogenesis, Stata DX, and the University of Basel outside the submitted work. Dr. Fox reported receiving consulting fees from Siemens and Roche.
A version of this article appeared on Medscape.com.
FROM JAMA NEUROLOGY
Salt intake associated with increased type 2 diabetes risk
TOPLINE:
, even after adjustment for confounding factors.
METHODOLOGY:
- Researchers identified 402,982 participants in the UK Biobank from March 2006 to October 2010 who had completed a questionnaire about the frequency with which they added salt to food and who did not have diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline.
- Urine samples were collected at baseline, sodium and potassium levels were measured, and 24-hour sodium excretion was estimated.
- Investigators followed participants from baseline to diagnosis of diabetes, death, or the censoring date (May 23, 2021), whichever occurred first. Information on T2D events were collected through medical history linkage to data on hospital admissions, questionnaire, and the death register.
TAKEAWAY:
- During a mean follow-up of 11.9 years, 13,120 incident cases of T2D were documented.
- Compared with people who reported “never/rarely” adding salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P-trend < .001).
- After further adjustment for the Townsend deprivation index, education level, income, smoking, drinking, physical activity, and high cholesterol, the association was attenuated but remained significant, with HRs of 1.11, 1.18, and 1.28 for “sometimes,” “usually,” and “always” responses, respectively (P-trend < .001).
- After full adjustment, there was also a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34 for quintiles 2-5, respectively (P-trend < .001).
- Body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, by estimated effects of 37.9% and 39.9%, respectively (both P < .001).
IN PRACTICE:
“These findings provide support that reduction of adding salt to foods may act as a potential behavioral intervention approach for preventing T2D. Future clinical trials are needed to further validate our findings,” the authors wrote.
SOURCE:
The study by Xuan Wang, MD, PhD, department of epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, and colleagues was published in the November 2023 issue of Mayo Clinic Proceedings.
LIMITATIONS:
The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle. Self-reported frequency of adding salt to food might be subject to information bias and did not provide quantitative information on total sodium intake. In addition, participants were mainly of European descent, making application of the findings to other ethnic groups unclear; the observational design meant researchers could not rule out residual confounding; and information on addition of salt to food was available only at baseline, so potential changes in salt consumption during follow-up could not be considered.
DISCLOSURES:
The study was supported by grants from the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the Fogarty International Center; and Tulane Research Centers of Excellence Awards. The authors reported no potential competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
, even after adjustment for confounding factors.
METHODOLOGY:
- Researchers identified 402,982 participants in the UK Biobank from March 2006 to October 2010 who had completed a questionnaire about the frequency with which they added salt to food and who did not have diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline.
- Urine samples were collected at baseline, sodium and potassium levels were measured, and 24-hour sodium excretion was estimated.
- Investigators followed participants from baseline to diagnosis of diabetes, death, or the censoring date (May 23, 2021), whichever occurred first. Information on T2D events were collected through medical history linkage to data on hospital admissions, questionnaire, and the death register.
TAKEAWAY:
- During a mean follow-up of 11.9 years, 13,120 incident cases of T2D were documented.
- Compared with people who reported “never/rarely” adding salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P-trend < .001).
- After further adjustment for the Townsend deprivation index, education level, income, smoking, drinking, physical activity, and high cholesterol, the association was attenuated but remained significant, with HRs of 1.11, 1.18, and 1.28 for “sometimes,” “usually,” and “always” responses, respectively (P-trend < .001).
- After full adjustment, there was also a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34 for quintiles 2-5, respectively (P-trend < .001).
- Body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, by estimated effects of 37.9% and 39.9%, respectively (both P < .001).
IN PRACTICE:
“These findings provide support that reduction of adding salt to foods may act as a potential behavioral intervention approach for preventing T2D. Future clinical trials are needed to further validate our findings,” the authors wrote.
SOURCE:
The study by Xuan Wang, MD, PhD, department of epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, and colleagues was published in the November 2023 issue of Mayo Clinic Proceedings.
LIMITATIONS:
The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle. Self-reported frequency of adding salt to food might be subject to information bias and did not provide quantitative information on total sodium intake. In addition, participants were mainly of European descent, making application of the findings to other ethnic groups unclear; the observational design meant researchers could not rule out residual confounding; and information on addition of salt to food was available only at baseline, so potential changes in salt consumption during follow-up could not be considered.
DISCLOSURES:
The study was supported by grants from the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the Fogarty International Center; and Tulane Research Centers of Excellence Awards. The authors reported no potential competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
, even after adjustment for confounding factors.
METHODOLOGY:
- Researchers identified 402,982 participants in the UK Biobank from March 2006 to October 2010 who had completed a questionnaire about the frequency with which they added salt to food and who did not have diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline.
- Urine samples were collected at baseline, sodium and potassium levels were measured, and 24-hour sodium excretion was estimated.
- Investigators followed participants from baseline to diagnosis of diabetes, death, or the censoring date (May 23, 2021), whichever occurred first. Information on T2D events were collected through medical history linkage to data on hospital admissions, questionnaire, and the death register.
TAKEAWAY:
- During a mean follow-up of 11.9 years, 13,120 incident cases of T2D were documented.
- Compared with people who reported “never/rarely” adding salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P-trend < .001).
- After further adjustment for the Townsend deprivation index, education level, income, smoking, drinking, physical activity, and high cholesterol, the association was attenuated but remained significant, with HRs of 1.11, 1.18, and 1.28 for “sometimes,” “usually,” and “always” responses, respectively (P-trend < .001).
- After full adjustment, there was also a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34 for quintiles 2-5, respectively (P-trend < .001).
- Body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, by estimated effects of 37.9% and 39.9%, respectively (both P < .001).
IN PRACTICE:
“These findings provide support that reduction of adding salt to foods may act as a potential behavioral intervention approach for preventing T2D. Future clinical trials are needed to further validate our findings,” the authors wrote.
SOURCE:
The study by Xuan Wang, MD, PhD, department of epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, and colleagues was published in the November 2023 issue of Mayo Clinic Proceedings.
LIMITATIONS:
The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle. Self-reported frequency of adding salt to food might be subject to information bias and did not provide quantitative information on total sodium intake. In addition, participants were mainly of European descent, making application of the findings to other ethnic groups unclear; the observational design meant researchers could not rule out residual confounding; and information on addition of salt to food was available only at baseline, so potential changes in salt consumption during follow-up could not be considered.
DISCLOSURES:
The study was supported by grants from the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the Fogarty International Center; and Tulane Research Centers of Excellence Awards. The authors reported no potential competing interests.
A version of this article appeared on Medscape.com.
RNA therapeutics will ‘change everything’ in epilepsy
Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.
But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.
“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.
Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.
Dr. Kaye said.
Thank COVID?
Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.
Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.
Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.
RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.
Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.
“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.
“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
Hope for Dravet syndrome
Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.
Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.
The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.
“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.
Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.
“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.
“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.
“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
A promising future
Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”
And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.
Take, for example, a case reported recently in the New England Journal of Medicine.
Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.
One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.
However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”
“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.
The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.
A version of this article first appeared on Medscape.com.
Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.
But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.
“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.
Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.
Dr. Kaye said.
Thank COVID?
Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.
Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.
Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.
RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.
Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.
“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.
“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
Hope for Dravet syndrome
Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.
Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.
The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.
“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.
Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.
“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.
“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.
“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
A promising future
Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”
And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.
Take, for example, a case reported recently in the New England Journal of Medicine.
Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.
One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.
However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”
“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.
The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.
A version of this article first appeared on Medscape.com.
Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.
But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.
“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.
Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.
Dr. Kaye said.
Thank COVID?
Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.
Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.
Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.
RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.
Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.
“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.
“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
Hope for Dravet syndrome
Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.
Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.
The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.
“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.
Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.
“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.
“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.
“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
A promising future
Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”
And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.
Take, for example, a case reported recently in the New England Journal of Medicine.
Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.
One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.
However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”
“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.
The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.
A version of this article first appeared on Medscape.com.
Does diabetes affect colorectal cancer outcomes?
TOPLINE:
, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.
METHODOLOGY:
- This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
- The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
- The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
TAKEAWAY:
- Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
- Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
- Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
- Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.
IN PRACTICE:
“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.
SOURCE:
The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.
LIMITATIONS:
Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.
DISCLOSURES:
Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.
METHODOLOGY:
- This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
- The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
- The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
TAKEAWAY:
- Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
- Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
- Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
- Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.
IN PRACTICE:
“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.
SOURCE:
The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.
LIMITATIONS:
Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.
DISCLOSURES:
Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.
METHODOLOGY:
- This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
- The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
- The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
TAKEAWAY:
- Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
- Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
- Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
- Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.
IN PRACTICE:
“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.
SOURCE:
The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.
LIMITATIONS:
Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.
DISCLOSURES:
Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Childhood trauma linked to adult headache
TOPLINE:
with more early adverse experiences raising the risk even more, a new study found.
METHODOLOGY:
- The meta-analysis included 28 observational studies with 154,739 persons in 19 countries that assessed the relationship between at least one adverse childhood experience (ACE) and primary headache (including migraine, tension-type headache, cluster headache, and chronic/severe headache) at age 21 years or older.
- From each study, researchers extracted outcome point estimates and corresponding 95% confidence intervals, number of events in each group, and covariates included in the model. They subcategorized ACEs according to those involving threat (for example, physical, emotional, or sexual abuse) and deprivation (for example, neglect, household substance misuse).
- For the primary analysis, the researchers calculated the odds ratios and hazard ratios of headache among persons with at least one ACE, compared with those with no ACEs.
- They also tested an underlying biological theory that threat and deprivation ACEs may manifest differently in neurodevelopment, with distinct impacts on primary headaches.
TAKEAWAY:
- The most commonly reported ACEs were physical abuse (77%), sexual abuse (73%), and exposure to family violence (38%).
- Compared with having experienced no ACEs, experiencing at least one was associated with primary headaches (pooled OR, 1.48; 95% confidence interval, 1.36-1.61).
- As the number of ACEs increased, the strength of the association with primary headaches increased in a dose-response relationship (P for trend < .0001).
- Both threat and deprivation were independently associated with primary headaches; the pooled main effect was consistent for threat (OR, 1.46; 95% CI, 1.32-1.60) and for deprivation (OR, 1.35; 95% CI, 1.23-1.49), suggesting possible distinct pathways of early adversity.
IN PRACTICE:
Clinicians who treat primary headaches in adults “should routinely screen for ACEs, educate patients on the connection between ACEs and health, and provide referrals for treatment strategies,” the investigators write. Strategies such as trauma-informed or attachment-based therapy may help rewire parts of the brain that have been dysregulated, they add.
SOURCE:
The study was led by Claudia Sikorski, department of health research methods, evidence, and impact, McMaster University, Hamilton, Ont. It was published online in Neurology.
LIMITATIONS:
The findings reflect a conservative estimate of the true impact of ACEs on primary headaches, because ACEs are commonly underreported. The analysis could not statistically disentangle younger adults with developing brains (age 21-26 years) from older adults. Not all included studies adjusted for age and sex, which are known risk factors for headaches. The study did not explore the relationship between ACEs and primary headache disorders in childhood and adolescence. Owing to the inherent nature of studies investigating ACEs, causation cannot be inferred.
DISCLOSURES:
The authors report no targeted funding and no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
with more early adverse experiences raising the risk even more, a new study found.
METHODOLOGY:
- The meta-analysis included 28 observational studies with 154,739 persons in 19 countries that assessed the relationship between at least one adverse childhood experience (ACE) and primary headache (including migraine, tension-type headache, cluster headache, and chronic/severe headache) at age 21 years or older.
- From each study, researchers extracted outcome point estimates and corresponding 95% confidence intervals, number of events in each group, and covariates included in the model. They subcategorized ACEs according to those involving threat (for example, physical, emotional, or sexual abuse) and deprivation (for example, neglect, household substance misuse).
- For the primary analysis, the researchers calculated the odds ratios and hazard ratios of headache among persons with at least one ACE, compared with those with no ACEs.
- They also tested an underlying biological theory that threat and deprivation ACEs may manifest differently in neurodevelopment, with distinct impacts on primary headaches.
TAKEAWAY:
- The most commonly reported ACEs were physical abuse (77%), sexual abuse (73%), and exposure to family violence (38%).
- Compared with having experienced no ACEs, experiencing at least one was associated with primary headaches (pooled OR, 1.48; 95% confidence interval, 1.36-1.61).
- As the number of ACEs increased, the strength of the association with primary headaches increased in a dose-response relationship (P for trend < .0001).
- Both threat and deprivation were independently associated with primary headaches; the pooled main effect was consistent for threat (OR, 1.46; 95% CI, 1.32-1.60) and for deprivation (OR, 1.35; 95% CI, 1.23-1.49), suggesting possible distinct pathways of early adversity.
IN PRACTICE:
Clinicians who treat primary headaches in adults “should routinely screen for ACEs, educate patients on the connection between ACEs and health, and provide referrals for treatment strategies,” the investigators write. Strategies such as trauma-informed or attachment-based therapy may help rewire parts of the brain that have been dysregulated, they add.
SOURCE:
The study was led by Claudia Sikorski, department of health research methods, evidence, and impact, McMaster University, Hamilton, Ont. It was published online in Neurology.
LIMITATIONS:
The findings reflect a conservative estimate of the true impact of ACEs on primary headaches, because ACEs are commonly underreported. The analysis could not statistically disentangle younger adults with developing brains (age 21-26 years) from older adults. Not all included studies adjusted for age and sex, which are known risk factors for headaches. The study did not explore the relationship between ACEs and primary headache disorders in childhood and adolescence. Owing to the inherent nature of studies investigating ACEs, causation cannot be inferred.
DISCLOSURES:
The authors report no targeted funding and no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
with more early adverse experiences raising the risk even more, a new study found.
METHODOLOGY:
- The meta-analysis included 28 observational studies with 154,739 persons in 19 countries that assessed the relationship between at least one adverse childhood experience (ACE) and primary headache (including migraine, tension-type headache, cluster headache, and chronic/severe headache) at age 21 years or older.
- From each study, researchers extracted outcome point estimates and corresponding 95% confidence intervals, number of events in each group, and covariates included in the model. They subcategorized ACEs according to those involving threat (for example, physical, emotional, or sexual abuse) and deprivation (for example, neglect, household substance misuse).
- For the primary analysis, the researchers calculated the odds ratios and hazard ratios of headache among persons with at least one ACE, compared with those with no ACEs.
- They also tested an underlying biological theory that threat and deprivation ACEs may manifest differently in neurodevelopment, with distinct impacts on primary headaches.
TAKEAWAY:
- The most commonly reported ACEs were physical abuse (77%), sexual abuse (73%), and exposure to family violence (38%).
- Compared with having experienced no ACEs, experiencing at least one was associated with primary headaches (pooled OR, 1.48; 95% confidence interval, 1.36-1.61).
- As the number of ACEs increased, the strength of the association with primary headaches increased in a dose-response relationship (P for trend < .0001).
- Both threat and deprivation were independently associated with primary headaches; the pooled main effect was consistent for threat (OR, 1.46; 95% CI, 1.32-1.60) and for deprivation (OR, 1.35; 95% CI, 1.23-1.49), suggesting possible distinct pathways of early adversity.
IN PRACTICE:
Clinicians who treat primary headaches in adults “should routinely screen for ACEs, educate patients on the connection between ACEs and health, and provide referrals for treatment strategies,” the investigators write. Strategies such as trauma-informed or attachment-based therapy may help rewire parts of the brain that have been dysregulated, they add.
SOURCE:
The study was led by Claudia Sikorski, department of health research methods, evidence, and impact, McMaster University, Hamilton, Ont. It was published online in Neurology.
LIMITATIONS:
The findings reflect a conservative estimate of the true impact of ACEs on primary headaches, because ACEs are commonly underreported. The analysis could not statistically disentangle younger adults with developing brains (age 21-26 years) from older adults. Not all included studies adjusted for age and sex, which are known risk factors for headaches. The study did not explore the relationship between ACEs and primary headache disorders in childhood and adolescence. Owing to the inherent nature of studies investigating ACEs, causation cannot be inferred.
DISCLOSURES:
The authors report no targeted funding and no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Higher triglycerides linked to lower dementia risk
TOPLINE:
a large study of community-dwelling older adults suggests.
METHODOLOGY:
- The analysis included 18,294 participants, median age 75 years and median triglyceride level 106 mg/dL, from the Aspirin in Reducing Events in the Elderly (ASPREE) study, a placebo-controlled, randomized trial of daily low-dose aspirin in older people without dementia or history of cardiovascular disease (CVD) at recruitment.
- Researchers repeated their main analyses in a sub-cohort of 13,976 subjects with APOE epsilon-4 genetic data, and an external cohort of 68,200 participants, mean age 66.9 years and a median nonfasting triglyceride of 139 mg/dL, from the UK biobank, followed for a median of 12.5 years.
- The main outcome was incident dementia over 6.4 years and secondary outcomes included changes in composite cognitive function and domain-specific cognition.
- Researchers controlled for a number of potential confounders, including age, sex, race, smoking, alcohol consumption, education, family history of dementia, diabetes, hypertension, and statin use.
TAKEAWAY:
- Every doubling of baseline triglycerides was associated with an 18% lower risk of incident dementia across the entire study cohort (adjusted hazard ratio, 0.82) and in participants with genotypic data (aHR, 0.82) and a 17% lower risk in the external UK Biobank cohort (aHR, 0.83) (P ≤ .01 for all).
- In the entire cohort, the risk for dementia was 15% lower in those with triglyceride levels at 63-106 mg/dL (aHR, 0.85); 24% lower in those at 107-186 mg/dL (aHR, 0.76); and 36% lower for those with levels higher than 187 mg/dL (aHR, 0.64), compared with individuals with levels below 62 mg/dL (P for trend <.001).
- The direction and magnitude of the inverse association between triglycerides and dementia risk were not modified by age, sex, or risk factors related to triglycerides or dementia.
- In the entire study cohort, higher triglyceride levels were significantly associated with slower decline in global cognition (P = .02), composite cognition (P = .03), and a borderline significantly slower decline in episodic memory (P = .05).
IN PRACTICE:
“Triglyceride levels may serve as a useful predictor for dementia risk and cognitive decline in older populations,” the investigators write. Higher triglyceride levels may reflect better overall health and/or lifestyle behaviors that protect against dementia.
SOURCE:
The study was led by Zhen Zhou, of Monash University, Melbourne. It was published online in Neurology.
LIMITATIONS:
The study can’t establish a causal relationship between triglyceride levels and dementia or fully exclude reverse causality. As most ASPREE participants had normal to high-normal triglyceride levels, the results can’t be generalized to those with severe hypertriglyceridemia. The findings are unique to older people without CVD and may not be generalizable to other populations.
DISCLOSURES:
The study received support from the Royal Australian College of General Practitioners (RACGP)/HCF Research Foundation. Dr. Zhou reported receiving salary from the RACGP/HCF Research Foundation.
A version of this article first appeared on Medscape.com.
TOPLINE:
a large study of community-dwelling older adults suggests.
METHODOLOGY:
- The analysis included 18,294 participants, median age 75 years and median triglyceride level 106 mg/dL, from the Aspirin in Reducing Events in the Elderly (ASPREE) study, a placebo-controlled, randomized trial of daily low-dose aspirin in older people without dementia or history of cardiovascular disease (CVD) at recruitment.
- Researchers repeated their main analyses in a sub-cohort of 13,976 subjects with APOE epsilon-4 genetic data, and an external cohort of 68,200 participants, mean age 66.9 years and a median nonfasting triglyceride of 139 mg/dL, from the UK biobank, followed for a median of 12.5 years.
- The main outcome was incident dementia over 6.4 years and secondary outcomes included changes in composite cognitive function and domain-specific cognition.
- Researchers controlled for a number of potential confounders, including age, sex, race, smoking, alcohol consumption, education, family history of dementia, diabetes, hypertension, and statin use.
TAKEAWAY:
- Every doubling of baseline triglycerides was associated with an 18% lower risk of incident dementia across the entire study cohort (adjusted hazard ratio, 0.82) and in participants with genotypic data (aHR, 0.82) and a 17% lower risk in the external UK Biobank cohort (aHR, 0.83) (P ≤ .01 for all).
- In the entire cohort, the risk for dementia was 15% lower in those with triglyceride levels at 63-106 mg/dL (aHR, 0.85); 24% lower in those at 107-186 mg/dL (aHR, 0.76); and 36% lower for those with levels higher than 187 mg/dL (aHR, 0.64), compared with individuals with levels below 62 mg/dL (P for trend <.001).
- The direction and magnitude of the inverse association between triglycerides and dementia risk were not modified by age, sex, or risk factors related to triglycerides or dementia.
- In the entire study cohort, higher triglyceride levels were significantly associated with slower decline in global cognition (P = .02), composite cognition (P = .03), and a borderline significantly slower decline in episodic memory (P = .05).
IN PRACTICE:
“Triglyceride levels may serve as a useful predictor for dementia risk and cognitive decline in older populations,” the investigators write. Higher triglyceride levels may reflect better overall health and/or lifestyle behaviors that protect against dementia.
SOURCE:
The study was led by Zhen Zhou, of Monash University, Melbourne. It was published online in Neurology.
LIMITATIONS:
The study can’t establish a causal relationship between triglyceride levels and dementia or fully exclude reverse causality. As most ASPREE participants had normal to high-normal triglyceride levels, the results can’t be generalized to those with severe hypertriglyceridemia. The findings are unique to older people without CVD and may not be generalizable to other populations.
DISCLOSURES:
The study received support from the Royal Australian College of General Practitioners (RACGP)/HCF Research Foundation. Dr. Zhou reported receiving salary from the RACGP/HCF Research Foundation.
A version of this article first appeared on Medscape.com.
TOPLINE:
a large study of community-dwelling older adults suggests.
METHODOLOGY:
- The analysis included 18,294 participants, median age 75 years and median triglyceride level 106 mg/dL, from the Aspirin in Reducing Events in the Elderly (ASPREE) study, a placebo-controlled, randomized trial of daily low-dose aspirin in older people without dementia or history of cardiovascular disease (CVD) at recruitment.
- Researchers repeated their main analyses in a sub-cohort of 13,976 subjects with APOE epsilon-4 genetic data, and an external cohort of 68,200 participants, mean age 66.9 years and a median nonfasting triglyceride of 139 mg/dL, from the UK biobank, followed for a median of 12.5 years.
- The main outcome was incident dementia over 6.4 years and secondary outcomes included changes in composite cognitive function and domain-specific cognition.
- Researchers controlled for a number of potential confounders, including age, sex, race, smoking, alcohol consumption, education, family history of dementia, diabetes, hypertension, and statin use.
TAKEAWAY:
- Every doubling of baseline triglycerides was associated with an 18% lower risk of incident dementia across the entire study cohort (adjusted hazard ratio, 0.82) and in participants with genotypic data (aHR, 0.82) and a 17% lower risk in the external UK Biobank cohort (aHR, 0.83) (P ≤ .01 for all).
- In the entire cohort, the risk for dementia was 15% lower in those with triglyceride levels at 63-106 mg/dL (aHR, 0.85); 24% lower in those at 107-186 mg/dL (aHR, 0.76); and 36% lower for those with levels higher than 187 mg/dL (aHR, 0.64), compared with individuals with levels below 62 mg/dL (P for trend <.001).
- The direction and magnitude of the inverse association between triglycerides and dementia risk were not modified by age, sex, or risk factors related to triglycerides or dementia.
- In the entire study cohort, higher triglyceride levels were significantly associated with slower decline in global cognition (P = .02), composite cognition (P = .03), and a borderline significantly slower decline in episodic memory (P = .05).
IN PRACTICE:
“Triglyceride levels may serve as a useful predictor for dementia risk and cognitive decline in older populations,” the investigators write. Higher triglyceride levels may reflect better overall health and/or lifestyle behaviors that protect against dementia.
SOURCE:
The study was led by Zhen Zhou, of Monash University, Melbourne. It was published online in Neurology.
LIMITATIONS:
The study can’t establish a causal relationship between triglyceride levels and dementia or fully exclude reverse causality. As most ASPREE participants had normal to high-normal triglyceride levels, the results can’t be generalized to those with severe hypertriglyceridemia. The findings are unique to older people without CVD and may not be generalizable to other populations.
DISCLOSURES:
The study received support from the Royal Australian College of General Practitioners (RACGP)/HCF Research Foundation. Dr. Zhou reported receiving salary from the RACGP/HCF Research Foundation.
A version of this article first appeared on Medscape.com.
Another study ties statins to T2D: Should practice change?
Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”
Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.
For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”
They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”
An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”
In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
Rosuvastatin versus Atorvastatin
The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.
Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.
Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, (2.5% vs. 1.5%; HR, 1.66).
Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).
“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”
“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”
Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”
The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”
“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”
Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”
“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.
“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”
“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”
“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.”
So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.
One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.
Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.
With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:
- For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
- For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
- For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.
It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.
Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.
A version of this article appeared on Medscape.com.
Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”
Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.
For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”
They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”
An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”
In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
Rosuvastatin versus Atorvastatin
The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.
Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.
Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, (2.5% vs. 1.5%; HR, 1.66).
Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).
“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”
“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”
Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”
The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”
“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”
Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”
“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.
“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”
“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”
“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.”
So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.
One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.
Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.
With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:
- For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
- For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
- For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.
It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.
Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.
A version of this article appeared on Medscape.com.
Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”
Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.
For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”
They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”
An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”
In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
Rosuvastatin versus Atorvastatin
The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.
Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.
Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, (2.5% vs. 1.5%; HR, 1.66).
Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).
“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”
“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”
Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”
The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”
“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”
Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”
“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.
“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”
“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”
“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.”
So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.
One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.
Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.
With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:
- For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
- For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
- For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.
It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.
Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.
A version of this article appeared on Medscape.com.