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Noted oncologist ponders death, life, care inequities
In 2020, he published a book aimed at cancer specialists and their patients on how to die “with hope and dignity,” titled “Between Life and Death” (Penguin Random House India).
When Dr. Patel, the CEO of Carolina Blood and Cancer Care Associates in Rock Hill, S.C., became president of the Washington-based Community Oncology Alliance 2 years ago, he stepped into a leadership role in community oncology. As an advocate for health care payment reform on Capitol Hill, the South Carolina legislature, and within his own practice, Dr. Patel has long worked to eliminate disparities in U.S. cancer care.
This news organization spoke with Dr. Patel about his unusual career path.
Question: Your father had a great influence on you. Can you tell us more about him?
Answer: My dad was a hermit and a saint. He lost his dad when he was 4 years old and moved to the big city with his cousins. When he was 9 or so, he got a message saying that his mum was very ill. So, he and his cousin raised some money, got a doctor and one of those old, rugged jeeps, and they started driving to the village, but rains had destroyed the road. So, without penicillin, his mum died of pneumonia.
He felt that roads and doctor access were the two big factors that could have saved her life. He eventually became the Superintending Engineer for four districts in Gujarat State, building roads connecting every village, but he never gave up his simplistic, minimalist life.
When I was in elementary school, every other weekend my dad would literally dump me at the Mahatma Gandhi Ashram and come back in 2 hours. So, I’m looking at Gandhi’s cabinets, his pictures, reading about his life. So, my formative years were born in that.
Q: I read that you were intending to become an engineer and join the space race. How did your father nudge you toward medicine?
A: When I was 9 years old, my favorite movie hero died of cancer. To comfort me, my father inserted the idea into my brain: When you grow up, you can become a doctor to cure cancer. So, when I finished high school, I was 24th in the state and had an option to go to the space school in India. On the day when I was going for the interview, I could see tears in my father’s eyes, and he said, You know what, boy? I thought you’re going to become a doctor and cure cancer. So, to honor him, I went to med school instead.
Q: I understand that your father also triggered your interest in photography?
A: I started photographing Kutchi tribal people in 1977, after I bought a camera from a famous architect [Hasmukh Patel], while traveling with my dad. And then my dad bought me a motorcycle, so I started riding myself. From the time I entered med school in 1978 until I finished my residency in 1987, I made several trips following Kutchi migrant families and livestock. They leave their homeland in Kutch [district] during summer in search of grass and water to keep their livestock alive and walk across the state from the desert of Kutch all the way to central Gujarat until monsoon begins. Then they return, only to resume the journey next year. I would catch them along their journey, would talk to them, drink tea and eat millet crepes with them.
In 1984, between Dr. Patel’s medical school and residency, the Lions Club in his hometown, Ahmedabad, India, sponsored him and three buddies to document people and wildlife in Gujarat state. Traveling by motorcycle, the four friends stayed for free with local families by knocking on doors and explaining that they were medical students. Dr. Patel’s photographs were exhibited by the Lions Club of Ahmedabad and at India’s top art institution, the Lalit Kala gallery.
In the 3rd year of his internal-medicine residency in Bombay (now Mumbai), Dr. Patel approached a national newspaper, The Indian Express, for work. He was immediately sent on assignment to cover a cholera epidemic and filed his story and photographs the following day. He worked as a photojournalist and subeditor for a year.
Q: Among all your thousands of pictures, do you have a favorite?
A: There were two photos of Kutchi people that touched me. There was one photo of a lady. All of her worldly belongings were in the picture and a smile on her face showed that we don’t need so many things to be happy. The second photo is of an elderly lady shifting her water pan on her head to a younger family member. And a little girl looks up with a look of curiosity: Will I be doing this when I grow up? We seek so much materialistic happiness. But when you look at the curiosity, smiles, and happiness [in these photos], you realize we could have a lot of happiness in minimalism, as well.
Q: After you finished your residency in Ahmedabad, how did you get started in oncology?
A: In 1986, Ahmedabad City and Gujarat State did not have structured training programs in oncology, so I went to Bombay [Mumbai], where Dr. B.C. Mehta, a true legend and pioneer in India, had started hematology-oncology training. I was a post-doc research fellow with him for a little over a year but when I started seeing patients, I had to answer to myself, Am I doing everything I can to help these people? I saw that the U.K. had one of the best training programs in hem malignancy, so I started applying. Then something happened that was almost like a miracle.
In April 1992, Dr. Patel was working at the Institute of Kidney Diseases in Ahmedabad. One afternoon, just as the clinic was closing for siesta, a family brought in a young girl. She had drug-induced thrombocytopenia and needed an immediate transfusion. The father offered to sell his wedding ring to pay Dr. Patel if he would supervise the treatment and stay by the girl’s side. Dr. Patel told the man to keep his ring, then he remained in the office with the child. At 4 p.m., the office phone rang. It was Dr. H.K. Parikh, an eminent British physician who was wintering in India and needed to make a medical appointment for his wife. On a normal day, Dr. Patel would have missed the call.
“This is how I got to meet Dr. Parikh, out of the blue,” said Dr. Patel. “His wife came to the office for 6 weeks and after 6 weeks, he said, You’re a smart guy; you should come to England. That was in April. I sent a resume and all the usual paperwork. On July 16, 1992, at 2 in the morning, I got a call from the U.K. saying, Your job is confirmed. I’m going to fax your appointment through the Royal College of Physicians, and you’re coming to Manchester to work with us. I’d been sponsored by the Overseas Doctors Training Program.
“So, it turns out that if I’d declined to see that patient and declined to stay in my clinic that afternoon, if I’d declined to see this doctor’s wife, I would never have been in the U.K. And that opened up the doors for me. I like that story because I’ve found that standing up for people who do not have a voice, who do not have hope, always leads to what is destined for me.”
Q: After working as a registrar in the United Kingdom 4 years, you found yourself in the United States and, once again, had to train as an internist. What was new about U.S. oncology?
A: I took 3 years to get recertified in Jamaica Hospital in Queens, then became a fellow in hematology-oncology at the Thomas Jefferson in Philadelphia. My U.K. training was all based on hematological malignancy. In the United States, I shifted into solid tumors.
Q: You have a long history of advocating for affordable oncology at the community, state, and federal level, and you recently launched a disparities initiative in your center called NOLA (No One Left Alone). What was the trigger for NOLA?
A: In the spring of 2020, when we started seeing the COVID surge and the difference in mortality rate between the multiple races, at the same time I saw the AACR [American Association for Cancer Research] 2020 disparity report showing that 34% of cancer deaths are preventable – one in three – if we took care of disparities. The same year, the Community Oncology Alliance asked me to become the president. So, I felt that there is something herding me, leading me, to this position. Eighty percent of cancer patients are treated in community clinics like ours. It put the onus on me to do something.
I learned from Gandhi that I cannot depend on government, I cannot depend on the policy, I have to act myself.
I said, I would not worry about making money, I would rather lose funding on this. So, we started. I read 400+ papers; I spent over 1,000 hours reading about disparities. And I realized that it’s not complicated. There are five pillars to eliminate disparity: access to care for financial reasons, access to biomarker testing or precision medicine, access to social determinants of health, access to cancer screening, and trials. If we focus on these five, we can at least bring that number from 34% to 20%, if not lower.
So, we put that plan in place. I dedicated three employees whose only role is to ensure that not a single patient has to take financial burden from my practice. And we showed it’s doable.
This has now become my mission for the last quarter of my life.
In 2020, Dr. Patel published a book on dying well titled “Between Life and Death.” It’s framed as a series of his conversations with a former patient, Harry Falls. Harry wanted to understand death better, so Dr. Patel narrated five patient stories, drawing the threads together to help Harry face the inevitable. Dr. Patel now uses a similar approach to train clinicians on having meaningful end-of-life conversations with patients.
Q: Why did you feel the need to write a book about dying?
A: The more I’ve witnessed, the more I’m convinced that there are things that we don’t know about this process, which needs to be explored much more. However, I do feel that there’s a power within all of us to steer the process of leaving this world.
Before I sat down with Harry, I loved to counsel patients, but I didn’t have any structural ideas. It was Harry himself who told me that I now had a simple way to explain dying to a much larger audience.
Q: What is your secret for fitting everything into your life?
A: I’ll tell you, it’s very simple. If I put my soul, heart, mind, actions, and language on the one plane and don’t let my brain and conditioning influence my choices, then I live in the moment. Whenever I let my conditioned mind take all the decisions, those are crooked, because you know, we’re selfish creatures – we can use what we call the convenient lie to hide inconvenient truth. And I try not to do that. I mean, it’s been a journey. It didn’t come overnight. I learned. And I feel that over all these years, the only thing that rewarded me, that opened the door of where I am today, was pure, selfless process, whether it’s the act of talking, speaking, or doing.
In 2020, he published a book aimed at cancer specialists and their patients on how to die “with hope and dignity,” titled “Between Life and Death” (Penguin Random House India).
When Dr. Patel, the CEO of Carolina Blood and Cancer Care Associates in Rock Hill, S.C., became president of the Washington-based Community Oncology Alliance 2 years ago, he stepped into a leadership role in community oncology. As an advocate for health care payment reform on Capitol Hill, the South Carolina legislature, and within his own practice, Dr. Patel has long worked to eliminate disparities in U.S. cancer care.
This news organization spoke with Dr. Patel about his unusual career path.
Question: Your father had a great influence on you. Can you tell us more about him?
Answer: My dad was a hermit and a saint. He lost his dad when he was 4 years old and moved to the big city with his cousins. When he was 9 or so, he got a message saying that his mum was very ill. So, he and his cousin raised some money, got a doctor and one of those old, rugged jeeps, and they started driving to the village, but rains had destroyed the road. So, without penicillin, his mum died of pneumonia.
He felt that roads and doctor access were the two big factors that could have saved her life. He eventually became the Superintending Engineer for four districts in Gujarat State, building roads connecting every village, but he never gave up his simplistic, minimalist life.
When I was in elementary school, every other weekend my dad would literally dump me at the Mahatma Gandhi Ashram and come back in 2 hours. So, I’m looking at Gandhi’s cabinets, his pictures, reading about his life. So, my formative years were born in that.
Q: I read that you were intending to become an engineer and join the space race. How did your father nudge you toward medicine?
A: When I was 9 years old, my favorite movie hero died of cancer. To comfort me, my father inserted the idea into my brain: When you grow up, you can become a doctor to cure cancer. So, when I finished high school, I was 24th in the state and had an option to go to the space school in India. On the day when I was going for the interview, I could see tears in my father’s eyes, and he said, You know what, boy? I thought you’re going to become a doctor and cure cancer. So, to honor him, I went to med school instead.
Q: I understand that your father also triggered your interest in photography?
A: I started photographing Kutchi tribal people in 1977, after I bought a camera from a famous architect [Hasmukh Patel], while traveling with my dad. And then my dad bought me a motorcycle, so I started riding myself. From the time I entered med school in 1978 until I finished my residency in 1987, I made several trips following Kutchi migrant families and livestock. They leave their homeland in Kutch [district] during summer in search of grass and water to keep their livestock alive and walk across the state from the desert of Kutch all the way to central Gujarat until monsoon begins. Then they return, only to resume the journey next year. I would catch them along their journey, would talk to them, drink tea and eat millet crepes with them.
In 1984, between Dr. Patel’s medical school and residency, the Lions Club in his hometown, Ahmedabad, India, sponsored him and three buddies to document people and wildlife in Gujarat state. Traveling by motorcycle, the four friends stayed for free with local families by knocking on doors and explaining that they were medical students. Dr. Patel’s photographs were exhibited by the Lions Club of Ahmedabad and at India’s top art institution, the Lalit Kala gallery.
In the 3rd year of his internal-medicine residency in Bombay (now Mumbai), Dr. Patel approached a national newspaper, The Indian Express, for work. He was immediately sent on assignment to cover a cholera epidemic and filed his story and photographs the following day. He worked as a photojournalist and subeditor for a year.
Q: Among all your thousands of pictures, do you have a favorite?
A: There were two photos of Kutchi people that touched me. There was one photo of a lady. All of her worldly belongings were in the picture and a smile on her face showed that we don’t need so many things to be happy. The second photo is of an elderly lady shifting her water pan on her head to a younger family member. And a little girl looks up with a look of curiosity: Will I be doing this when I grow up? We seek so much materialistic happiness. But when you look at the curiosity, smiles, and happiness [in these photos], you realize we could have a lot of happiness in minimalism, as well.
Q: After you finished your residency in Ahmedabad, how did you get started in oncology?
A: In 1986, Ahmedabad City and Gujarat State did not have structured training programs in oncology, so I went to Bombay [Mumbai], where Dr. B.C. Mehta, a true legend and pioneer in India, had started hematology-oncology training. I was a post-doc research fellow with him for a little over a year but when I started seeing patients, I had to answer to myself, Am I doing everything I can to help these people? I saw that the U.K. had one of the best training programs in hem malignancy, so I started applying. Then something happened that was almost like a miracle.
In April 1992, Dr. Patel was working at the Institute of Kidney Diseases in Ahmedabad. One afternoon, just as the clinic was closing for siesta, a family brought in a young girl. She had drug-induced thrombocytopenia and needed an immediate transfusion. The father offered to sell his wedding ring to pay Dr. Patel if he would supervise the treatment and stay by the girl’s side. Dr. Patel told the man to keep his ring, then he remained in the office with the child. At 4 p.m., the office phone rang. It was Dr. H.K. Parikh, an eminent British physician who was wintering in India and needed to make a medical appointment for his wife. On a normal day, Dr. Patel would have missed the call.
“This is how I got to meet Dr. Parikh, out of the blue,” said Dr. Patel. “His wife came to the office for 6 weeks and after 6 weeks, he said, You’re a smart guy; you should come to England. That was in April. I sent a resume and all the usual paperwork. On July 16, 1992, at 2 in the morning, I got a call from the U.K. saying, Your job is confirmed. I’m going to fax your appointment through the Royal College of Physicians, and you’re coming to Manchester to work with us. I’d been sponsored by the Overseas Doctors Training Program.
“So, it turns out that if I’d declined to see that patient and declined to stay in my clinic that afternoon, if I’d declined to see this doctor’s wife, I would never have been in the U.K. And that opened up the doors for me. I like that story because I’ve found that standing up for people who do not have a voice, who do not have hope, always leads to what is destined for me.”
Q: After working as a registrar in the United Kingdom 4 years, you found yourself in the United States and, once again, had to train as an internist. What was new about U.S. oncology?
A: I took 3 years to get recertified in Jamaica Hospital in Queens, then became a fellow in hematology-oncology at the Thomas Jefferson in Philadelphia. My U.K. training was all based on hematological malignancy. In the United States, I shifted into solid tumors.
Q: You have a long history of advocating for affordable oncology at the community, state, and federal level, and you recently launched a disparities initiative in your center called NOLA (No One Left Alone). What was the trigger for NOLA?
A: In the spring of 2020, when we started seeing the COVID surge and the difference in mortality rate between the multiple races, at the same time I saw the AACR [American Association for Cancer Research] 2020 disparity report showing that 34% of cancer deaths are preventable – one in three – if we took care of disparities. The same year, the Community Oncology Alliance asked me to become the president. So, I felt that there is something herding me, leading me, to this position. Eighty percent of cancer patients are treated in community clinics like ours. It put the onus on me to do something.
I learned from Gandhi that I cannot depend on government, I cannot depend on the policy, I have to act myself.
I said, I would not worry about making money, I would rather lose funding on this. So, we started. I read 400+ papers; I spent over 1,000 hours reading about disparities. And I realized that it’s not complicated. There are five pillars to eliminate disparity: access to care for financial reasons, access to biomarker testing or precision medicine, access to social determinants of health, access to cancer screening, and trials. If we focus on these five, we can at least bring that number from 34% to 20%, if not lower.
So, we put that plan in place. I dedicated three employees whose only role is to ensure that not a single patient has to take financial burden from my practice. And we showed it’s doable.
This has now become my mission for the last quarter of my life.
In 2020, Dr. Patel published a book on dying well titled “Between Life and Death.” It’s framed as a series of his conversations with a former patient, Harry Falls. Harry wanted to understand death better, so Dr. Patel narrated five patient stories, drawing the threads together to help Harry face the inevitable. Dr. Patel now uses a similar approach to train clinicians on having meaningful end-of-life conversations with patients.
Q: Why did you feel the need to write a book about dying?
A: The more I’ve witnessed, the more I’m convinced that there are things that we don’t know about this process, which needs to be explored much more. However, I do feel that there’s a power within all of us to steer the process of leaving this world.
Before I sat down with Harry, I loved to counsel patients, but I didn’t have any structural ideas. It was Harry himself who told me that I now had a simple way to explain dying to a much larger audience.
Q: What is your secret for fitting everything into your life?
A: I’ll tell you, it’s very simple. If I put my soul, heart, mind, actions, and language on the one plane and don’t let my brain and conditioning influence my choices, then I live in the moment. Whenever I let my conditioned mind take all the decisions, those are crooked, because you know, we’re selfish creatures – we can use what we call the convenient lie to hide inconvenient truth. And I try not to do that. I mean, it’s been a journey. It didn’t come overnight. I learned. And I feel that over all these years, the only thing that rewarded me, that opened the door of where I am today, was pure, selfless process, whether it’s the act of talking, speaking, or doing.
In 2020, he published a book aimed at cancer specialists and their patients on how to die “with hope and dignity,” titled “Between Life and Death” (Penguin Random House India).
When Dr. Patel, the CEO of Carolina Blood and Cancer Care Associates in Rock Hill, S.C., became president of the Washington-based Community Oncology Alliance 2 years ago, he stepped into a leadership role in community oncology. As an advocate for health care payment reform on Capitol Hill, the South Carolina legislature, and within his own practice, Dr. Patel has long worked to eliminate disparities in U.S. cancer care.
This news organization spoke with Dr. Patel about his unusual career path.
Question: Your father had a great influence on you. Can you tell us more about him?
Answer: My dad was a hermit and a saint. He lost his dad when he was 4 years old and moved to the big city with his cousins. When he was 9 or so, he got a message saying that his mum was very ill. So, he and his cousin raised some money, got a doctor and one of those old, rugged jeeps, and they started driving to the village, but rains had destroyed the road. So, without penicillin, his mum died of pneumonia.
He felt that roads and doctor access were the two big factors that could have saved her life. He eventually became the Superintending Engineer for four districts in Gujarat State, building roads connecting every village, but he never gave up his simplistic, minimalist life.
When I was in elementary school, every other weekend my dad would literally dump me at the Mahatma Gandhi Ashram and come back in 2 hours. So, I’m looking at Gandhi’s cabinets, his pictures, reading about his life. So, my formative years were born in that.
Q: I read that you were intending to become an engineer and join the space race. How did your father nudge you toward medicine?
A: When I was 9 years old, my favorite movie hero died of cancer. To comfort me, my father inserted the idea into my brain: When you grow up, you can become a doctor to cure cancer. So, when I finished high school, I was 24th in the state and had an option to go to the space school in India. On the day when I was going for the interview, I could see tears in my father’s eyes, and he said, You know what, boy? I thought you’re going to become a doctor and cure cancer. So, to honor him, I went to med school instead.
Q: I understand that your father also triggered your interest in photography?
A: I started photographing Kutchi tribal people in 1977, after I bought a camera from a famous architect [Hasmukh Patel], while traveling with my dad. And then my dad bought me a motorcycle, so I started riding myself. From the time I entered med school in 1978 until I finished my residency in 1987, I made several trips following Kutchi migrant families and livestock. They leave their homeland in Kutch [district] during summer in search of grass and water to keep their livestock alive and walk across the state from the desert of Kutch all the way to central Gujarat until monsoon begins. Then they return, only to resume the journey next year. I would catch them along their journey, would talk to them, drink tea and eat millet crepes with them.
In 1984, between Dr. Patel’s medical school and residency, the Lions Club in his hometown, Ahmedabad, India, sponsored him and three buddies to document people and wildlife in Gujarat state. Traveling by motorcycle, the four friends stayed for free with local families by knocking on doors and explaining that they were medical students. Dr. Patel’s photographs were exhibited by the Lions Club of Ahmedabad and at India’s top art institution, the Lalit Kala gallery.
In the 3rd year of his internal-medicine residency in Bombay (now Mumbai), Dr. Patel approached a national newspaper, The Indian Express, for work. He was immediately sent on assignment to cover a cholera epidemic and filed his story and photographs the following day. He worked as a photojournalist and subeditor for a year.
Q: Among all your thousands of pictures, do you have a favorite?
A: There were two photos of Kutchi people that touched me. There was one photo of a lady. All of her worldly belongings were in the picture and a smile on her face showed that we don’t need so many things to be happy. The second photo is of an elderly lady shifting her water pan on her head to a younger family member. And a little girl looks up with a look of curiosity: Will I be doing this when I grow up? We seek so much materialistic happiness. But when you look at the curiosity, smiles, and happiness [in these photos], you realize we could have a lot of happiness in minimalism, as well.
Q: After you finished your residency in Ahmedabad, how did you get started in oncology?
A: In 1986, Ahmedabad City and Gujarat State did not have structured training programs in oncology, so I went to Bombay [Mumbai], where Dr. B.C. Mehta, a true legend and pioneer in India, had started hematology-oncology training. I was a post-doc research fellow with him for a little over a year but when I started seeing patients, I had to answer to myself, Am I doing everything I can to help these people? I saw that the U.K. had one of the best training programs in hem malignancy, so I started applying. Then something happened that was almost like a miracle.
In April 1992, Dr. Patel was working at the Institute of Kidney Diseases in Ahmedabad. One afternoon, just as the clinic was closing for siesta, a family brought in a young girl. She had drug-induced thrombocytopenia and needed an immediate transfusion. The father offered to sell his wedding ring to pay Dr. Patel if he would supervise the treatment and stay by the girl’s side. Dr. Patel told the man to keep his ring, then he remained in the office with the child. At 4 p.m., the office phone rang. It was Dr. H.K. Parikh, an eminent British physician who was wintering in India and needed to make a medical appointment for his wife. On a normal day, Dr. Patel would have missed the call.
“This is how I got to meet Dr. Parikh, out of the blue,” said Dr. Patel. “His wife came to the office for 6 weeks and after 6 weeks, he said, You’re a smart guy; you should come to England. That was in April. I sent a resume and all the usual paperwork. On July 16, 1992, at 2 in the morning, I got a call from the U.K. saying, Your job is confirmed. I’m going to fax your appointment through the Royal College of Physicians, and you’re coming to Manchester to work with us. I’d been sponsored by the Overseas Doctors Training Program.
“So, it turns out that if I’d declined to see that patient and declined to stay in my clinic that afternoon, if I’d declined to see this doctor’s wife, I would never have been in the U.K. And that opened up the doors for me. I like that story because I’ve found that standing up for people who do not have a voice, who do not have hope, always leads to what is destined for me.”
Q: After working as a registrar in the United Kingdom 4 years, you found yourself in the United States and, once again, had to train as an internist. What was new about U.S. oncology?
A: I took 3 years to get recertified in Jamaica Hospital in Queens, then became a fellow in hematology-oncology at the Thomas Jefferson in Philadelphia. My U.K. training was all based on hematological malignancy. In the United States, I shifted into solid tumors.
Q: You have a long history of advocating for affordable oncology at the community, state, and federal level, and you recently launched a disparities initiative in your center called NOLA (No One Left Alone). What was the trigger for NOLA?
A: In the spring of 2020, when we started seeing the COVID surge and the difference in mortality rate between the multiple races, at the same time I saw the AACR [American Association for Cancer Research] 2020 disparity report showing that 34% of cancer deaths are preventable – one in three – if we took care of disparities. The same year, the Community Oncology Alliance asked me to become the president. So, I felt that there is something herding me, leading me, to this position. Eighty percent of cancer patients are treated in community clinics like ours. It put the onus on me to do something.
I learned from Gandhi that I cannot depend on government, I cannot depend on the policy, I have to act myself.
I said, I would not worry about making money, I would rather lose funding on this. So, we started. I read 400+ papers; I spent over 1,000 hours reading about disparities. And I realized that it’s not complicated. There are five pillars to eliminate disparity: access to care for financial reasons, access to biomarker testing or precision medicine, access to social determinants of health, access to cancer screening, and trials. If we focus on these five, we can at least bring that number from 34% to 20%, if not lower.
So, we put that plan in place. I dedicated three employees whose only role is to ensure that not a single patient has to take financial burden from my practice. And we showed it’s doable.
This has now become my mission for the last quarter of my life.
In 2020, Dr. Patel published a book on dying well titled “Between Life and Death.” It’s framed as a series of his conversations with a former patient, Harry Falls. Harry wanted to understand death better, so Dr. Patel narrated five patient stories, drawing the threads together to help Harry face the inevitable. Dr. Patel now uses a similar approach to train clinicians on having meaningful end-of-life conversations with patients.
Q: Why did you feel the need to write a book about dying?
A: The more I’ve witnessed, the more I’m convinced that there are things that we don’t know about this process, which needs to be explored much more. However, I do feel that there’s a power within all of us to steer the process of leaving this world.
Before I sat down with Harry, I loved to counsel patients, but I didn’t have any structural ideas. It was Harry himself who told me that I now had a simple way to explain dying to a much larger audience.
Q: What is your secret for fitting everything into your life?
A: I’ll tell you, it’s very simple. If I put my soul, heart, mind, actions, and language on the one plane and don’t let my brain and conditioning influence my choices, then I live in the moment. Whenever I let my conditioned mind take all the decisions, those are crooked, because you know, we’re selfish creatures – we can use what we call the convenient lie to hide inconvenient truth. And I try not to do that. I mean, it’s been a journey. It didn’t come overnight. I learned. And I feel that over all these years, the only thing that rewarded me, that opened the door of where I am today, was pure, selfless process, whether it’s the act of talking, speaking, or doing.
Shift in child hospice care is a lifeline for parents seeking a measure of comfort and hope
POMONA, CALIF. – When you first meet 17-month-old Aaron Martinez, it’s not obvious that something is catastrophically wrong.
What you see is a beautiful little boy with smooth, lustrous skin, an abundance of glossy brown hair, and a disarming smile. What you hear are coos and cries that don’t immediately signal anything is horribly awry.
But his parents, Adriana Pinedo and Hector Martinez, know the truth painfully well.
Although Ms. Pinedo’s doctors and midwife had described the pregnancy as “perfect” for all 9 months, Aaron was born with most of his brain cells dead, the result of two strokes and a massive bleed he sustained while in utero.
Doctors aren’t sure what caused the anomalies that left Aaron with virtually no cognitive function or physical mobility. His voluminous hair hides a head whose circumference is too small for his age. He has epilepsy that triggers multiple seizures each day, and his smile is not always what it seems. “It could be a smile; it could be a seizure,” Ms. Pinedo said.
Shortly after Aaron was born, doctors told Ms. Pinedo, 34, and Mr. Martinez, 35, there was no hope and they should “let nature take its course.” They would learn months later that the doctors had not expected the boy to live more than 5 days. It was on Day 5 that his parents put him in home hospice care, an arrangement that has continued into his second year of life.
The family gets weekly visits from hospice nurses, therapists, social workers, and a chaplain in the cramped one-bedroom apartment they rent from the people who live in the main house on the same lot on a quiet residential street in this Inland Empire city.
One of the main criteria for hospice care, established by Medicare largely for seniors but also applied to children, is a diagnosis of 6 months or less to live. Yet over the course of 17 months, Aaron’s medical team has repeatedly recertified his hospice eligibility.
Under a provision of the 2010 Affordable Care Act, children enrolled in Medicaid or the Children’s Health Insurance Program are allowed, unlike adults, to be in hospice while continuing to receive curative or life-extending care. Commercial insurers are not required to cover this “concurrent care,” but many now do.
More than a decade since its inception, concurrent care is widely credited with improving the quality of life for many terminally ill children, easing stress on the family and, in some cases, sustaining hope for a cure. But the arrangement can contribute to a painful dilemma for parents like Ms. Pinedo and Mr. Martinez, who are torn between their fierce commitment to their son and the futility of knowing that his condition leaves him with no future worth hoping for.
“We could lose a life, but if he continues to live this way, we’ll lose three,” said Ms. Pinedo. “There’s no quality of life for him or for us.”
Aaron’s doctors now say he could conceivably live for years. His body hasn’t stopped growing since he was born. He’s in the 96th percentile for height for his age, and his weight is about average.
His parents have talked about “graduating” him from hospice. But he is never stable for long, and they welcome the visits from their hospice team. The seizures, sometimes 30 a day, are a persistent assault on his brain and, as he grows, the medications intended to control them must be changed or the doses recalibrated. He is at continual risk of gastrointestinal problems and potentially deadly fluid buildup in his lungs.
Ms. Pinedo, who works from home for a nonprofit public health organization, spends much of her time with Aaron, while Mr. Martinez works as a landscaper. She has chosen to live in the moment, she said, because otherwise her mind wanders to a future in which either “he could die – or he won’t, and I’ll end up changing the diapers of a 40-year-old man.” Either of those “are going to suck.”
While cancer is one of the major illnesses afflicting children in hospice, many others, like Aaron, have rare congenital defects, severe neurological impairments, or uncommon metabolic deficiencies.
“We have diseases that families tell us are 1 of 10 cases in the world,” said Glen Komatsu, MD, medical director of Torrance, Calif.–based TrinityKids Care, which provides home hospice services to Aaron and more than 70 other kids in Los Angeles and Orange counties.
In the years leading up to the ACA’s implementation, pediatric health advocates lobbied hard for the concurrent care provision. Without the possibility of life-extending care or hope for a cure, many parents refused to put their terminally ill kids in hospice, thinking it was tantamount to giving up on them. That meant the whole family missed out on the support hospice can provide, not just pain relief and comfort for the dying child, but emotional and spiritual care for parents and siblings under extreme duress.
TrinityKids Care, run by the large national Catholic health system Providence, doesn’t just send nurses, social workers, and chaplains into homes. For patients able to participate, and their siblings, it also offers art and science projects, exercise classes, movies, and music. During the pandemic, these activities have been conducted via Zoom, and volunteers deliver needed supplies to the children’s homes.
The ability to get treatments that prolong their lives is a major reason children in concurrent care are more likely than adults to outlive the 6-months-to-live diagnosis required for hospice.
“Concurrent care, by its very intention, very clearly is going to extend their lives, and by extending their lives they’re no longer going to be hospice-eligible if you use the 6-month life expectancy criteria,” said David Steinhorn, MD, a pediatric intensive care physician in Virginia, who has helped develop numerous children’s hospice programs across the United States.
Another factor is that kids, even sick ones, are simply more robust than many older people.
“Sick kids are often otherwise healthy, except for one organ,” said Debra Lotstein, MD, chief of the division of comfort and palliative care at Children’s Hospital Los Angeles. “They may have cancer in their body, but their hearts are good and their lungs are good, compared to a 90-year-old who at baseline is just not as resilient.”
All of Aaron Martinez’s vital organs, except for his brain, seem to be working. “There have been times when we’ve brought him in, and the nurse looks at the chart and looks at him, and she can’t believe it’s that child,” said Mr. Martinez.
When kids live past the 6-month life expectancy, they must be recertified to stay in hospice. In many cases, Dr. Steinhorn said, he is willing to recertify his pediatric patients indefinitely.
Even with doctors advocating for them, it’s not always easy for children to get into hospice care. Most hospices care primarily for adults and are reluctant to take kids.
“The hospice will say: ‘We don’t have the capacity to treat children. Our nurses aren’t trained. It’s different. We just can’t do it,’ ” said Lori Butterworth, cofounder of the Children’s Hospice and Palliative Care Coalition of California in Watsonville. “The other reason is not wanting to, because it’s existentially devastating and sad and hard.”
Finances also play a role. Home hospice care is paid at a per diem rate set by Medicare – slightly over $200 a day for the first 2 months, about $161 a day after that – and it is typically the same for kids and adults. Children, particularly those with rare conditions, often require more intensive and innovative care, so the per diem doesn’t stretch as far.
The concurrent care provision has made taking pediatric patients more viable for hospice organizations, Dr. Steinhorn and others said. Under the ACA, many of the expenses for certain medications and medical services can be shifted to the patient’s primary insurance, leaving hospices responsible for pain relief and comfort care.
Even so, the relatively small number of kids who die each year from protracted ailments hardly makes pediatric hospice an appealing line of business in an industry craving growth, especially one in which private equity investors are active and seeking a big payday.
In California, only 21 of 1,336 hospices reported having a specialized pediatric hospice program, and 59 said they served at least one patient under age 21, according to an analysis of 2020 state data by Cordt Kassner, CEO of Hospice Analytics in Colorado Springs.
Hospice providers that do cater to children often face a more basic challenge: Even with the possibility of concurrent care, many parents still equate hospice with acceptance of death. That was the case initially for Matt and Reese Sonnen, Los Angeles residents whose daughter, Layla, was born with a seizure disorder that had no name: Her brain had simply failed to develop in the womb, and an MRI showed “fluid taking up space where the brain wasn’t,” her mother said.
When Layla’s team first mentioned hospice, “I was in the car on my phone, and I almost crashed the car,” Mrs. Sonnen recalled. “The first thought that came to mind was: ‘It is just the end,’ but we felt she was nowhere near it, because she was strong, she was mighty. She was my little girl. She was going to get through this.”
About 3 months later, as Layla’s nervous system deteriorated, causing her to writhe in pain, her parents agreed to enroll her in hospice with TrinityKids Care. She died weeks later, not long after her second birthday. She was in her mother’s arms, with Mr. Sonnen close by.
“All of a sudden, Layla breathed out a big rush of air. The nurse looked at me and said: ‘That was her last breath.’ I was literally breathing in her last breath,” Mrs. Sonnen recounted. “I never wanted to breathe again, because now I felt I had her in my lungs. Don’t make me laugh, don’t make me exhale.”
Layla’s parents have no regrets about their decision to put her in hospice. “It was the absolute right decision, and in hindsight we should have done it sooner,” Mr. Sonnen said. “She was suffering, and we had blinders on.”
Ms. Pinedo said she is “infinitely grateful” for hospice, despite the heartache of Aaron’s condition. Sometimes the social worker will stop by, she said, just to say hello and drop off a latte, a small gesture that can feel very uplifting. “They’ve been our lifeline,” she said.
Ms. Pinedo talks about a friend of hers with a healthy baby, also named Aaron, who is pregnant with her second child. “All the stuff that was on our list, they’re living. And I love them dearly. But it’s almost hard to look, because it’s like looking at the stuff that you didn’t get. It’s like Christmas Day, staring through the window at the neighbor’s house, and you’re sitting there in the cold.”
Yet she seems palpably torn between that bleak remorse and the unconditional love parents feel toward their children. At one point, Ms. Pinedo interrupted herself midsentence and turned to her son, who was in Mr. Martinez’s arms: “Yes, Papi, you are so stinking cute, and you are still my dream come true.”
This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
POMONA, CALIF. – When you first meet 17-month-old Aaron Martinez, it’s not obvious that something is catastrophically wrong.
What you see is a beautiful little boy with smooth, lustrous skin, an abundance of glossy brown hair, and a disarming smile. What you hear are coos and cries that don’t immediately signal anything is horribly awry.
But his parents, Adriana Pinedo and Hector Martinez, know the truth painfully well.
Although Ms. Pinedo’s doctors and midwife had described the pregnancy as “perfect” for all 9 months, Aaron was born with most of his brain cells dead, the result of two strokes and a massive bleed he sustained while in utero.
Doctors aren’t sure what caused the anomalies that left Aaron with virtually no cognitive function or physical mobility. His voluminous hair hides a head whose circumference is too small for his age. He has epilepsy that triggers multiple seizures each day, and his smile is not always what it seems. “It could be a smile; it could be a seizure,” Ms. Pinedo said.
Shortly after Aaron was born, doctors told Ms. Pinedo, 34, and Mr. Martinez, 35, there was no hope and they should “let nature take its course.” They would learn months later that the doctors had not expected the boy to live more than 5 days. It was on Day 5 that his parents put him in home hospice care, an arrangement that has continued into his second year of life.
The family gets weekly visits from hospice nurses, therapists, social workers, and a chaplain in the cramped one-bedroom apartment they rent from the people who live in the main house on the same lot on a quiet residential street in this Inland Empire city.
One of the main criteria for hospice care, established by Medicare largely for seniors but also applied to children, is a diagnosis of 6 months or less to live. Yet over the course of 17 months, Aaron’s medical team has repeatedly recertified his hospice eligibility.
Under a provision of the 2010 Affordable Care Act, children enrolled in Medicaid or the Children’s Health Insurance Program are allowed, unlike adults, to be in hospice while continuing to receive curative or life-extending care. Commercial insurers are not required to cover this “concurrent care,” but many now do.
More than a decade since its inception, concurrent care is widely credited with improving the quality of life for many terminally ill children, easing stress on the family and, in some cases, sustaining hope for a cure. But the arrangement can contribute to a painful dilemma for parents like Ms. Pinedo and Mr. Martinez, who are torn between their fierce commitment to their son and the futility of knowing that his condition leaves him with no future worth hoping for.
“We could lose a life, but if he continues to live this way, we’ll lose three,” said Ms. Pinedo. “There’s no quality of life for him or for us.”
Aaron’s doctors now say he could conceivably live for years. His body hasn’t stopped growing since he was born. He’s in the 96th percentile for height for his age, and his weight is about average.
His parents have talked about “graduating” him from hospice. But he is never stable for long, and they welcome the visits from their hospice team. The seizures, sometimes 30 a day, are a persistent assault on his brain and, as he grows, the medications intended to control them must be changed or the doses recalibrated. He is at continual risk of gastrointestinal problems and potentially deadly fluid buildup in his lungs.
Ms. Pinedo, who works from home for a nonprofit public health organization, spends much of her time with Aaron, while Mr. Martinez works as a landscaper. She has chosen to live in the moment, she said, because otherwise her mind wanders to a future in which either “he could die – or he won’t, and I’ll end up changing the diapers of a 40-year-old man.” Either of those “are going to suck.”
While cancer is one of the major illnesses afflicting children in hospice, many others, like Aaron, have rare congenital defects, severe neurological impairments, or uncommon metabolic deficiencies.
“We have diseases that families tell us are 1 of 10 cases in the world,” said Glen Komatsu, MD, medical director of Torrance, Calif.–based TrinityKids Care, which provides home hospice services to Aaron and more than 70 other kids in Los Angeles and Orange counties.
In the years leading up to the ACA’s implementation, pediatric health advocates lobbied hard for the concurrent care provision. Without the possibility of life-extending care or hope for a cure, many parents refused to put their terminally ill kids in hospice, thinking it was tantamount to giving up on them. That meant the whole family missed out on the support hospice can provide, not just pain relief and comfort for the dying child, but emotional and spiritual care for parents and siblings under extreme duress.
TrinityKids Care, run by the large national Catholic health system Providence, doesn’t just send nurses, social workers, and chaplains into homes. For patients able to participate, and their siblings, it also offers art and science projects, exercise classes, movies, and music. During the pandemic, these activities have been conducted via Zoom, and volunteers deliver needed supplies to the children’s homes.
The ability to get treatments that prolong their lives is a major reason children in concurrent care are more likely than adults to outlive the 6-months-to-live diagnosis required for hospice.
“Concurrent care, by its very intention, very clearly is going to extend their lives, and by extending their lives they’re no longer going to be hospice-eligible if you use the 6-month life expectancy criteria,” said David Steinhorn, MD, a pediatric intensive care physician in Virginia, who has helped develop numerous children’s hospice programs across the United States.
Another factor is that kids, even sick ones, are simply more robust than many older people.
“Sick kids are often otherwise healthy, except for one organ,” said Debra Lotstein, MD, chief of the division of comfort and palliative care at Children’s Hospital Los Angeles. “They may have cancer in their body, but their hearts are good and their lungs are good, compared to a 90-year-old who at baseline is just not as resilient.”
All of Aaron Martinez’s vital organs, except for his brain, seem to be working. “There have been times when we’ve brought him in, and the nurse looks at the chart and looks at him, and she can’t believe it’s that child,” said Mr. Martinez.
When kids live past the 6-month life expectancy, they must be recertified to stay in hospice. In many cases, Dr. Steinhorn said, he is willing to recertify his pediatric patients indefinitely.
Even with doctors advocating for them, it’s not always easy for children to get into hospice care. Most hospices care primarily for adults and are reluctant to take kids.
“The hospice will say: ‘We don’t have the capacity to treat children. Our nurses aren’t trained. It’s different. We just can’t do it,’ ” said Lori Butterworth, cofounder of the Children’s Hospice and Palliative Care Coalition of California in Watsonville. “The other reason is not wanting to, because it’s existentially devastating and sad and hard.”
Finances also play a role. Home hospice care is paid at a per diem rate set by Medicare – slightly over $200 a day for the first 2 months, about $161 a day after that – and it is typically the same for kids and adults. Children, particularly those with rare conditions, often require more intensive and innovative care, so the per diem doesn’t stretch as far.
The concurrent care provision has made taking pediatric patients more viable for hospice organizations, Dr. Steinhorn and others said. Under the ACA, many of the expenses for certain medications and medical services can be shifted to the patient’s primary insurance, leaving hospices responsible for pain relief and comfort care.
Even so, the relatively small number of kids who die each year from protracted ailments hardly makes pediatric hospice an appealing line of business in an industry craving growth, especially one in which private equity investors are active and seeking a big payday.
In California, only 21 of 1,336 hospices reported having a specialized pediatric hospice program, and 59 said they served at least one patient under age 21, according to an analysis of 2020 state data by Cordt Kassner, CEO of Hospice Analytics in Colorado Springs.
Hospice providers that do cater to children often face a more basic challenge: Even with the possibility of concurrent care, many parents still equate hospice with acceptance of death. That was the case initially for Matt and Reese Sonnen, Los Angeles residents whose daughter, Layla, was born with a seizure disorder that had no name: Her brain had simply failed to develop in the womb, and an MRI showed “fluid taking up space where the brain wasn’t,” her mother said.
When Layla’s team first mentioned hospice, “I was in the car on my phone, and I almost crashed the car,” Mrs. Sonnen recalled. “The first thought that came to mind was: ‘It is just the end,’ but we felt she was nowhere near it, because she was strong, she was mighty. She was my little girl. She was going to get through this.”
About 3 months later, as Layla’s nervous system deteriorated, causing her to writhe in pain, her parents agreed to enroll her in hospice with TrinityKids Care. She died weeks later, not long after her second birthday. She was in her mother’s arms, with Mr. Sonnen close by.
“All of a sudden, Layla breathed out a big rush of air. The nurse looked at me and said: ‘That was her last breath.’ I was literally breathing in her last breath,” Mrs. Sonnen recounted. “I never wanted to breathe again, because now I felt I had her in my lungs. Don’t make me laugh, don’t make me exhale.”
Layla’s parents have no regrets about their decision to put her in hospice. “It was the absolute right decision, and in hindsight we should have done it sooner,” Mr. Sonnen said. “She was suffering, and we had blinders on.”
Ms. Pinedo said she is “infinitely grateful” for hospice, despite the heartache of Aaron’s condition. Sometimes the social worker will stop by, she said, just to say hello and drop off a latte, a small gesture that can feel very uplifting. “They’ve been our lifeline,” she said.
Ms. Pinedo talks about a friend of hers with a healthy baby, also named Aaron, who is pregnant with her second child. “All the stuff that was on our list, they’re living. And I love them dearly. But it’s almost hard to look, because it’s like looking at the stuff that you didn’t get. It’s like Christmas Day, staring through the window at the neighbor’s house, and you’re sitting there in the cold.”
Yet she seems palpably torn between that bleak remorse and the unconditional love parents feel toward their children. At one point, Ms. Pinedo interrupted herself midsentence and turned to her son, who was in Mr. Martinez’s arms: “Yes, Papi, you are so stinking cute, and you are still my dream come true.”
This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
POMONA, CALIF. – When you first meet 17-month-old Aaron Martinez, it’s not obvious that something is catastrophically wrong.
What you see is a beautiful little boy with smooth, lustrous skin, an abundance of glossy brown hair, and a disarming smile. What you hear are coos and cries that don’t immediately signal anything is horribly awry.
But his parents, Adriana Pinedo and Hector Martinez, know the truth painfully well.
Although Ms. Pinedo’s doctors and midwife had described the pregnancy as “perfect” for all 9 months, Aaron was born with most of his brain cells dead, the result of two strokes and a massive bleed he sustained while in utero.
Doctors aren’t sure what caused the anomalies that left Aaron with virtually no cognitive function or physical mobility. His voluminous hair hides a head whose circumference is too small for his age. He has epilepsy that triggers multiple seizures each day, and his smile is not always what it seems. “It could be a smile; it could be a seizure,” Ms. Pinedo said.
Shortly after Aaron was born, doctors told Ms. Pinedo, 34, and Mr. Martinez, 35, there was no hope and they should “let nature take its course.” They would learn months later that the doctors had not expected the boy to live more than 5 days. It was on Day 5 that his parents put him in home hospice care, an arrangement that has continued into his second year of life.
The family gets weekly visits from hospice nurses, therapists, social workers, and a chaplain in the cramped one-bedroom apartment they rent from the people who live in the main house on the same lot on a quiet residential street in this Inland Empire city.
One of the main criteria for hospice care, established by Medicare largely for seniors but also applied to children, is a diagnosis of 6 months or less to live. Yet over the course of 17 months, Aaron’s medical team has repeatedly recertified his hospice eligibility.
Under a provision of the 2010 Affordable Care Act, children enrolled in Medicaid or the Children’s Health Insurance Program are allowed, unlike adults, to be in hospice while continuing to receive curative or life-extending care. Commercial insurers are not required to cover this “concurrent care,” but many now do.
More than a decade since its inception, concurrent care is widely credited with improving the quality of life for many terminally ill children, easing stress on the family and, in some cases, sustaining hope for a cure. But the arrangement can contribute to a painful dilemma for parents like Ms. Pinedo and Mr. Martinez, who are torn between their fierce commitment to their son and the futility of knowing that his condition leaves him with no future worth hoping for.
“We could lose a life, but if he continues to live this way, we’ll lose three,” said Ms. Pinedo. “There’s no quality of life for him or for us.”
Aaron’s doctors now say he could conceivably live for years. His body hasn’t stopped growing since he was born. He’s in the 96th percentile for height for his age, and his weight is about average.
His parents have talked about “graduating” him from hospice. But he is never stable for long, and they welcome the visits from their hospice team. The seizures, sometimes 30 a day, are a persistent assault on his brain and, as he grows, the medications intended to control them must be changed or the doses recalibrated. He is at continual risk of gastrointestinal problems and potentially deadly fluid buildup in his lungs.
Ms. Pinedo, who works from home for a nonprofit public health organization, spends much of her time with Aaron, while Mr. Martinez works as a landscaper. She has chosen to live in the moment, she said, because otherwise her mind wanders to a future in which either “he could die – or he won’t, and I’ll end up changing the diapers of a 40-year-old man.” Either of those “are going to suck.”
While cancer is one of the major illnesses afflicting children in hospice, many others, like Aaron, have rare congenital defects, severe neurological impairments, or uncommon metabolic deficiencies.
“We have diseases that families tell us are 1 of 10 cases in the world,” said Glen Komatsu, MD, medical director of Torrance, Calif.–based TrinityKids Care, which provides home hospice services to Aaron and more than 70 other kids in Los Angeles and Orange counties.
In the years leading up to the ACA’s implementation, pediatric health advocates lobbied hard for the concurrent care provision. Without the possibility of life-extending care or hope for a cure, many parents refused to put their terminally ill kids in hospice, thinking it was tantamount to giving up on them. That meant the whole family missed out on the support hospice can provide, not just pain relief and comfort for the dying child, but emotional and spiritual care for parents and siblings under extreme duress.
TrinityKids Care, run by the large national Catholic health system Providence, doesn’t just send nurses, social workers, and chaplains into homes. For patients able to participate, and their siblings, it also offers art and science projects, exercise classes, movies, and music. During the pandemic, these activities have been conducted via Zoom, and volunteers deliver needed supplies to the children’s homes.
The ability to get treatments that prolong their lives is a major reason children in concurrent care are more likely than adults to outlive the 6-months-to-live diagnosis required for hospice.
“Concurrent care, by its very intention, very clearly is going to extend their lives, and by extending their lives they’re no longer going to be hospice-eligible if you use the 6-month life expectancy criteria,” said David Steinhorn, MD, a pediatric intensive care physician in Virginia, who has helped develop numerous children’s hospice programs across the United States.
Another factor is that kids, even sick ones, are simply more robust than many older people.
“Sick kids are often otherwise healthy, except for one organ,” said Debra Lotstein, MD, chief of the division of comfort and palliative care at Children’s Hospital Los Angeles. “They may have cancer in their body, but their hearts are good and their lungs are good, compared to a 90-year-old who at baseline is just not as resilient.”
All of Aaron Martinez’s vital organs, except for his brain, seem to be working. “There have been times when we’ve brought him in, and the nurse looks at the chart and looks at him, and she can’t believe it’s that child,” said Mr. Martinez.
When kids live past the 6-month life expectancy, they must be recertified to stay in hospice. In many cases, Dr. Steinhorn said, he is willing to recertify his pediatric patients indefinitely.
Even with doctors advocating for them, it’s not always easy for children to get into hospice care. Most hospices care primarily for adults and are reluctant to take kids.
“The hospice will say: ‘We don’t have the capacity to treat children. Our nurses aren’t trained. It’s different. We just can’t do it,’ ” said Lori Butterworth, cofounder of the Children’s Hospice and Palliative Care Coalition of California in Watsonville. “The other reason is not wanting to, because it’s existentially devastating and sad and hard.”
Finances also play a role. Home hospice care is paid at a per diem rate set by Medicare – slightly over $200 a day for the first 2 months, about $161 a day after that – and it is typically the same for kids and adults. Children, particularly those with rare conditions, often require more intensive and innovative care, so the per diem doesn’t stretch as far.
The concurrent care provision has made taking pediatric patients more viable for hospice organizations, Dr. Steinhorn and others said. Under the ACA, many of the expenses for certain medications and medical services can be shifted to the patient’s primary insurance, leaving hospices responsible for pain relief and comfort care.
Even so, the relatively small number of kids who die each year from protracted ailments hardly makes pediatric hospice an appealing line of business in an industry craving growth, especially one in which private equity investors are active and seeking a big payday.
In California, only 21 of 1,336 hospices reported having a specialized pediatric hospice program, and 59 said they served at least one patient under age 21, according to an analysis of 2020 state data by Cordt Kassner, CEO of Hospice Analytics in Colorado Springs.
Hospice providers that do cater to children often face a more basic challenge: Even with the possibility of concurrent care, many parents still equate hospice with acceptance of death. That was the case initially for Matt and Reese Sonnen, Los Angeles residents whose daughter, Layla, was born with a seizure disorder that had no name: Her brain had simply failed to develop in the womb, and an MRI showed “fluid taking up space where the brain wasn’t,” her mother said.
When Layla’s team first mentioned hospice, “I was in the car on my phone, and I almost crashed the car,” Mrs. Sonnen recalled. “The first thought that came to mind was: ‘It is just the end,’ but we felt she was nowhere near it, because she was strong, she was mighty. She was my little girl. She was going to get through this.”
About 3 months later, as Layla’s nervous system deteriorated, causing her to writhe in pain, her parents agreed to enroll her in hospice with TrinityKids Care. She died weeks later, not long after her second birthday. She was in her mother’s arms, with Mr. Sonnen close by.
“All of a sudden, Layla breathed out a big rush of air. The nurse looked at me and said: ‘That was her last breath.’ I was literally breathing in her last breath,” Mrs. Sonnen recounted. “I never wanted to breathe again, because now I felt I had her in my lungs. Don’t make me laugh, don’t make me exhale.”
Layla’s parents have no regrets about their decision to put her in hospice. “It was the absolute right decision, and in hindsight we should have done it sooner,” Mr. Sonnen said. “She was suffering, and we had blinders on.”
Ms. Pinedo said she is “infinitely grateful” for hospice, despite the heartache of Aaron’s condition. Sometimes the social worker will stop by, she said, just to say hello and drop off a latte, a small gesture that can feel very uplifting. “They’ve been our lifeline,” she said.
Ms. Pinedo talks about a friend of hers with a healthy baby, also named Aaron, who is pregnant with her second child. “All the stuff that was on our list, they’re living. And I love them dearly. But it’s almost hard to look, because it’s like looking at the stuff that you didn’t get. It’s like Christmas Day, staring through the window at the neighbor’s house, and you’re sitting there in the cold.”
Yet she seems palpably torn between that bleak remorse and the unconditional love parents feel toward their children. At one point, Ms. Pinedo interrupted herself midsentence and turned to her son, who was in Mr. Martinez’s arms: “Yes, Papi, you are so stinking cute, and you are still my dream come true.”
This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Mothers’ diabetes linked to ADHD in their children
Children born to women who develop diabetes either before or during their pregnancy could be at risk for developing attention-deficit/hyperactivity disorder, data from a large multinational cohort study appear to show.
Considering more than 4.5 million mother-child pairs, it was found that children whose mothers had diabetes around the time of their pregnancy were 16% more likely to have ADHD diagnosed than were those whose mothers did not.
An increased risk was seen regardless of the type of diabetes, and regardless of whether or not the diabetes was present before or appeared during the pregnancy.
“We found a small increased risk of ADHD in children born to mothers with diabetes, including pregestational diabetes and gestational diabetes,” Carolyn Cesta, PhD, reported at the annual meeting of the European Association for the Study of Diabetes.
Dr. Cesta, a postdoctoral researcher in the Centre for Pharmacoepidemiology at the Karolinska Institutet in Stockholm noted that the effect sizes seen were lower than had been reported previously.
“This may be because we adjusted for a large number of covariates, including maternal ADHD and psychiatric disorders,” Dr. Cesta said.
ADHD and diabetes
“Previous studies have reported an increase in the risk of ADHD in children born to mothers with diabetes,” explained Dr. Cesta.
However, “these studies have been limited by the use of self-reported data, small sample sizes, lack of adjustment for important confounders, and they’re often limited to [White] populations,” she added. “There’s a lot of heterogeneity between these studies,” she said.
To try to iron out the differences seen in the prior studies, Dr. Cesta and associates looked at data from several databases based in Hong Kong (Clinical Data Analysis and Reporting System), four Nordic countries (Population Health Registers for Finland, Iceland, Norway, and Sweden), and Taiwan (National Health Insurance Database).
To create the matched mother-child pairs, the databases were searched to find women who had children born between 2001 and 2018, and who had follow-up data available up to 2020 on not only their diabetes status and child’s ADHD status, but also other parameters, such as other maternal diagnoses, maternal medications, and a host of sociodemographic factors.
More than 24 potentially confounding or covariates were considered in the analysis, which used Cox proportional hazard regression modeling and propensity score analysis to calculate hazard ratios with 95% confidence intervals.
“We looked at whether [mothers] had a diagnosis of ADHD themselves, or other psychiatric disorders, because there is high heritability for these disorders,” Dr. Cesta said, indicating that all bases had endeavored to be covered.
Main findings
Results showed some differences in the prevalence of diabetes and ADHD between the three cohorts used in the analysis. The prevalence of any maternal diabetes ranged from 8.8% in the Hong Kong cohort to 3.3% in the Taiwan cohort, with a prevalence of 6.8% for the Nordic cohort.
Rates of pregestational diabetes were lowest in the Taiwan and Hong Kong cohorts, at 0.2% and 0.5%, respectively, and 2.2% in the Nordic cohort. Gestational diabetes rates were a respective 3.1%, 7.8%, and 4.6%.
The highest rate of ADHD in children was seen in the Taiwan cohort, at 9.6%, followed by 4.2% for the Hong Kong cohort, and 2.6% for the Nordic cohort.
The hazard ratio for having childhood ADHD was 1.16 when comparing any maternal diabetes to no maternal diabetes, 1.40 comparing mothers with and without pregestational diabetes, and a respective 1.36 and 1.37 comparing those with and without type 1 diabetes, and those with and without type 2 diabetes.
The HR for childhood ADHD comparing mothers with and without gestational diabetes was 1.13.
“Within the analysis for gestational diabetes, we had enough numbers to look at siblings that are discordant for maternal gestational diabetes,” Dr. Cesta said. Essentially “we’re comparing two siblings from the same mother, one that was exposed to gestational diabetes, one that wasn’t,” she explained.
Interestingly there was no association between ADHD and maternal gestational diabetes in the sibling analysis (HR, 1.0).
“When it comes to gestational diabetes, the evidence from our sibling analysis indicate that the association may actually be confounded by shared genetics and environmental factors,” said Dr. Cesta.
“So, future studies should explore the role of specific genetic factors in glycemic control during pregnancy and the relationship between maternal diabetes and ADHD.”
Answering long-standing questions
These data will help a lot in answering questions that clinicians have been asking themselves a long time, commented Jardena Puder, MD, who chaired the session.
“It still remains a bit puzzling that genetic and environmental factors could be responsible, if you see the same effect in type 1 [diabetes], and in type 2 [diabetes], and gestational diabetes,” said Dr. Puder, who is an endocrinologist and diabetologist at the woman-mother-child department at the Vaud University Hospital Center, Lausanne, Switzerland.
Type 1 and type 2 are “very distinct” in terms of the genetic and environmental factors involved, “so, the fact that you see [the effect] in both remains a bit puzzling,” said Dr. Puder.
“I wish we had the numbers to be able to do the sibling analysis for type 1 and type 2, just to see if we could tease anything out,” said Dr. Cesta.
“I do think this is part of the bigger question of what the relationship is between, like, metabolic disorders and psychiatric disorders, because even outside of pregnancy, we see that there’s often a comorbidity with them. So, it’s a good point.”
The next step is to look at the role of treatment and what effects glycemic control might have on the small, but still apparent, association between maternal diabetes and ADHD.
The study had multiple funders including the Hong Kong Research Grant Council, NordForsk, the Research Council of Norway, the Norwegian ADHD Research Network, the Hong Kong Innovation and Technology Commission, and European Horizon 2020.
Dr. Cesta had no conflicts of interest to disclose. Dr. Puder chaired the session in which the findings were presented and made no specific disclosures.
Children born to women who develop diabetes either before or during their pregnancy could be at risk for developing attention-deficit/hyperactivity disorder, data from a large multinational cohort study appear to show.
Considering more than 4.5 million mother-child pairs, it was found that children whose mothers had diabetes around the time of their pregnancy were 16% more likely to have ADHD diagnosed than were those whose mothers did not.
An increased risk was seen regardless of the type of diabetes, and regardless of whether or not the diabetes was present before or appeared during the pregnancy.
“We found a small increased risk of ADHD in children born to mothers with diabetes, including pregestational diabetes and gestational diabetes,” Carolyn Cesta, PhD, reported at the annual meeting of the European Association for the Study of Diabetes.
Dr. Cesta, a postdoctoral researcher in the Centre for Pharmacoepidemiology at the Karolinska Institutet in Stockholm noted that the effect sizes seen were lower than had been reported previously.
“This may be because we adjusted for a large number of covariates, including maternal ADHD and psychiatric disorders,” Dr. Cesta said.
ADHD and diabetes
“Previous studies have reported an increase in the risk of ADHD in children born to mothers with diabetes,” explained Dr. Cesta.
However, “these studies have been limited by the use of self-reported data, small sample sizes, lack of adjustment for important confounders, and they’re often limited to [White] populations,” she added. “There’s a lot of heterogeneity between these studies,” she said.
To try to iron out the differences seen in the prior studies, Dr. Cesta and associates looked at data from several databases based in Hong Kong (Clinical Data Analysis and Reporting System), four Nordic countries (Population Health Registers for Finland, Iceland, Norway, and Sweden), and Taiwan (National Health Insurance Database).
To create the matched mother-child pairs, the databases were searched to find women who had children born between 2001 and 2018, and who had follow-up data available up to 2020 on not only their diabetes status and child’s ADHD status, but also other parameters, such as other maternal diagnoses, maternal medications, and a host of sociodemographic factors.
More than 24 potentially confounding or covariates were considered in the analysis, which used Cox proportional hazard regression modeling and propensity score analysis to calculate hazard ratios with 95% confidence intervals.
“We looked at whether [mothers] had a diagnosis of ADHD themselves, or other psychiatric disorders, because there is high heritability for these disorders,” Dr. Cesta said, indicating that all bases had endeavored to be covered.
Main findings
Results showed some differences in the prevalence of diabetes and ADHD between the three cohorts used in the analysis. The prevalence of any maternal diabetes ranged from 8.8% in the Hong Kong cohort to 3.3% in the Taiwan cohort, with a prevalence of 6.8% for the Nordic cohort.
Rates of pregestational diabetes were lowest in the Taiwan and Hong Kong cohorts, at 0.2% and 0.5%, respectively, and 2.2% in the Nordic cohort. Gestational diabetes rates were a respective 3.1%, 7.8%, and 4.6%.
The highest rate of ADHD in children was seen in the Taiwan cohort, at 9.6%, followed by 4.2% for the Hong Kong cohort, and 2.6% for the Nordic cohort.
The hazard ratio for having childhood ADHD was 1.16 when comparing any maternal diabetes to no maternal diabetes, 1.40 comparing mothers with and without pregestational diabetes, and a respective 1.36 and 1.37 comparing those with and without type 1 diabetes, and those with and without type 2 diabetes.
The HR for childhood ADHD comparing mothers with and without gestational diabetes was 1.13.
“Within the analysis for gestational diabetes, we had enough numbers to look at siblings that are discordant for maternal gestational diabetes,” Dr. Cesta said. Essentially “we’re comparing two siblings from the same mother, one that was exposed to gestational diabetes, one that wasn’t,” she explained.
Interestingly there was no association between ADHD and maternal gestational diabetes in the sibling analysis (HR, 1.0).
“When it comes to gestational diabetes, the evidence from our sibling analysis indicate that the association may actually be confounded by shared genetics and environmental factors,” said Dr. Cesta.
“So, future studies should explore the role of specific genetic factors in glycemic control during pregnancy and the relationship between maternal diabetes and ADHD.”
Answering long-standing questions
These data will help a lot in answering questions that clinicians have been asking themselves a long time, commented Jardena Puder, MD, who chaired the session.
“It still remains a bit puzzling that genetic and environmental factors could be responsible, if you see the same effect in type 1 [diabetes], and in type 2 [diabetes], and gestational diabetes,” said Dr. Puder, who is an endocrinologist and diabetologist at the woman-mother-child department at the Vaud University Hospital Center, Lausanne, Switzerland.
Type 1 and type 2 are “very distinct” in terms of the genetic and environmental factors involved, “so, the fact that you see [the effect] in both remains a bit puzzling,” said Dr. Puder.
“I wish we had the numbers to be able to do the sibling analysis for type 1 and type 2, just to see if we could tease anything out,” said Dr. Cesta.
“I do think this is part of the bigger question of what the relationship is between, like, metabolic disorders and psychiatric disorders, because even outside of pregnancy, we see that there’s often a comorbidity with them. So, it’s a good point.”
The next step is to look at the role of treatment and what effects glycemic control might have on the small, but still apparent, association between maternal diabetes and ADHD.
The study had multiple funders including the Hong Kong Research Grant Council, NordForsk, the Research Council of Norway, the Norwegian ADHD Research Network, the Hong Kong Innovation and Technology Commission, and European Horizon 2020.
Dr. Cesta had no conflicts of interest to disclose. Dr. Puder chaired the session in which the findings were presented and made no specific disclosures.
Children born to women who develop diabetes either before or during their pregnancy could be at risk for developing attention-deficit/hyperactivity disorder, data from a large multinational cohort study appear to show.
Considering more than 4.5 million mother-child pairs, it was found that children whose mothers had diabetes around the time of their pregnancy were 16% more likely to have ADHD diagnosed than were those whose mothers did not.
An increased risk was seen regardless of the type of diabetes, and regardless of whether or not the diabetes was present before or appeared during the pregnancy.
“We found a small increased risk of ADHD in children born to mothers with diabetes, including pregestational diabetes and gestational diabetes,” Carolyn Cesta, PhD, reported at the annual meeting of the European Association for the Study of Diabetes.
Dr. Cesta, a postdoctoral researcher in the Centre for Pharmacoepidemiology at the Karolinska Institutet in Stockholm noted that the effect sizes seen were lower than had been reported previously.
“This may be because we adjusted for a large number of covariates, including maternal ADHD and psychiatric disorders,” Dr. Cesta said.
ADHD and diabetes
“Previous studies have reported an increase in the risk of ADHD in children born to mothers with diabetes,” explained Dr. Cesta.
However, “these studies have been limited by the use of self-reported data, small sample sizes, lack of adjustment for important confounders, and they’re often limited to [White] populations,” she added. “There’s a lot of heterogeneity between these studies,” she said.
To try to iron out the differences seen in the prior studies, Dr. Cesta and associates looked at data from several databases based in Hong Kong (Clinical Data Analysis and Reporting System), four Nordic countries (Population Health Registers for Finland, Iceland, Norway, and Sweden), and Taiwan (National Health Insurance Database).
To create the matched mother-child pairs, the databases were searched to find women who had children born between 2001 and 2018, and who had follow-up data available up to 2020 on not only their diabetes status and child’s ADHD status, but also other parameters, such as other maternal diagnoses, maternal medications, and a host of sociodemographic factors.
More than 24 potentially confounding or covariates were considered in the analysis, which used Cox proportional hazard regression modeling and propensity score analysis to calculate hazard ratios with 95% confidence intervals.
“We looked at whether [mothers] had a diagnosis of ADHD themselves, or other psychiatric disorders, because there is high heritability for these disorders,” Dr. Cesta said, indicating that all bases had endeavored to be covered.
Main findings
Results showed some differences in the prevalence of diabetes and ADHD between the three cohorts used in the analysis. The prevalence of any maternal diabetes ranged from 8.8% in the Hong Kong cohort to 3.3% in the Taiwan cohort, with a prevalence of 6.8% for the Nordic cohort.
Rates of pregestational diabetes were lowest in the Taiwan and Hong Kong cohorts, at 0.2% and 0.5%, respectively, and 2.2% in the Nordic cohort. Gestational diabetes rates were a respective 3.1%, 7.8%, and 4.6%.
The highest rate of ADHD in children was seen in the Taiwan cohort, at 9.6%, followed by 4.2% for the Hong Kong cohort, and 2.6% for the Nordic cohort.
The hazard ratio for having childhood ADHD was 1.16 when comparing any maternal diabetes to no maternal diabetes, 1.40 comparing mothers with and without pregestational diabetes, and a respective 1.36 and 1.37 comparing those with and without type 1 diabetes, and those with and without type 2 diabetes.
The HR for childhood ADHD comparing mothers with and without gestational diabetes was 1.13.
“Within the analysis for gestational diabetes, we had enough numbers to look at siblings that are discordant for maternal gestational diabetes,” Dr. Cesta said. Essentially “we’re comparing two siblings from the same mother, one that was exposed to gestational diabetes, one that wasn’t,” she explained.
Interestingly there was no association between ADHD and maternal gestational diabetes in the sibling analysis (HR, 1.0).
“When it comes to gestational diabetes, the evidence from our sibling analysis indicate that the association may actually be confounded by shared genetics and environmental factors,” said Dr. Cesta.
“So, future studies should explore the role of specific genetic factors in glycemic control during pregnancy and the relationship between maternal diabetes and ADHD.”
Answering long-standing questions
These data will help a lot in answering questions that clinicians have been asking themselves a long time, commented Jardena Puder, MD, who chaired the session.
“It still remains a bit puzzling that genetic and environmental factors could be responsible, if you see the same effect in type 1 [diabetes], and in type 2 [diabetes], and gestational diabetes,” said Dr. Puder, who is an endocrinologist and diabetologist at the woman-mother-child department at the Vaud University Hospital Center, Lausanne, Switzerland.
Type 1 and type 2 are “very distinct” in terms of the genetic and environmental factors involved, “so, the fact that you see [the effect] in both remains a bit puzzling,” said Dr. Puder.
“I wish we had the numbers to be able to do the sibling analysis for type 1 and type 2, just to see if we could tease anything out,” said Dr. Cesta.
“I do think this is part of the bigger question of what the relationship is between, like, metabolic disorders and psychiatric disorders, because even outside of pregnancy, we see that there’s often a comorbidity with them. So, it’s a good point.”
The next step is to look at the role of treatment and what effects glycemic control might have on the small, but still apparent, association between maternal diabetes and ADHD.
The study had multiple funders including the Hong Kong Research Grant Council, NordForsk, the Research Council of Norway, the Norwegian ADHD Research Network, the Hong Kong Innovation and Technology Commission, and European Horizon 2020.
Dr. Cesta had no conflicts of interest to disclose. Dr. Puder chaired the session in which the findings were presented and made no specific disclosures.
FROM EASD 2022
Triple threat: Novel agent shows potent T2D weight loss in phase 1
STOCKHOLM – First came the GLP-1 receptor agonists as treatments for patients with type 2 diabetes, then came tirzepatide (Mounjaro) which added a second incretin agonism for the receptor to the glucose-dependent insulinotropic polypeptide (GIP). Now coming onto the clinical scene is a molecule with triple agonism to the GLP-1 receptor, the GIP receptor, and to the glucagon receptor.
That molecule, LY3437943, showed reasonable safety and tolerability and an apparent incremental uptick in weight loss compared with the approved incretin-based agents for people with type 2 diabetes in a 12-week, dose-ranging study involving a 52 patients with type 2 diabetes who received the new agent.
The 12 people who uptitrated for a total of 12 weeks and reached the highest tested dose of LY3437943, 12 mg, injected once weekly during the final 4 weeks, showed an average weight loss of 8.65 kg, while the 11 patients who maxed out at a weekly dose of 6 mg of LY3437943 had an average 12-week weight loss of 7.52 kg, Zvonko Milicevic, MD, reported at the annual meeting of the European Association for the Study of Diabetes.
Fifteen more participants received placebo and five received a comparator GLP-1 receptor agonist. All 72 patients in the study were also already on treatment with metformin when they entered, and they were maintained on metformin throughout the study period.
The new agent showed “greater weight loss efficacy than currently approved medications,” said Dr. Milicevic, a staff researcher who works in Vienna for Eli Lilly, the company developing LY3437943.
‘Really impressive’ weight loss
Martin Haluzik, MD, who chaired the session where Dr. Milicevic spoke, agreed. “The data, especially for weight reduction, were really impressive,” Dr. Haluzik said in an interview. “It looks stronger than the best we have at the moment,” the dual incretin agonist tirzepatide, he added.
Cross-study comparisons are very unreliable, but to put the weight loss seen with LY3437943 in perspective, the 12-week weight reduction that occurred with the highest dose of tirzepatide tested (15 mg/weekly) in the pivotal SURPASS-2 trial with 1,879 randomized patients with type 2 diabetes was an average of roughly 5 kg, while the comparator of 1 mg weekly of semaglutide (Ozempic) tested in the same study produced an average weight loss of about 4 kg.
Other notable efficacy results for LY3437943 after 12 weeks on treatment included an average reduction in hemoglobin A1c from baseline of 1.90%, achieved in the group that received 6 mg weekly as their maximum dose for 8 weeks after a 4-week run-in at a lower dose; a reduction in systolic blood pressure of 7.99 mm Hg on the 6-mg maximum weekly dose and of 12.06 mm Hg on the maximum 12-mg weekly dose; and “robust” reductions in lipids including cuts from baseline of about 40% for both triglycerides and very-LDL cholesterol, Dr. Milicevic reported.
Adverse effects resemble approved incretin-based agents
The study, which ran at four U.S. sites, had a primary objective of safety assessment, and Dr. Milicevic said the results showed acceptable safety and tolerability consistent with the glucagon-like peptide-1 (GLP-1) receptor agonists and tirzepatide. Like those agents, LY3437943 caused primarily mild gastrointestinal adverse effects such as nausea and diarrhea. Of the 52 patients in the study who received the triple agonist, 4 discontinued treatment because of a treatment-emergent adverse effect, including 1 patient in the subgroup who received the maximum dose.
The only concerning adverse effect noted by Dr. Haluzik was the average increase in heart rate from baseline of 10.26 beats/min in the subgroup that received the maximum dose, roughly twice the increase seen with tirzepatide and semaglutide in SURPASS-2. The average heart rate increase was about half that, 5.30 beats/min compared with baseline, in the subgroup that received a maximum weekly dose of 6 mg.
Overall, the results showed “no major adverse effects that might hamper use,” said Dr. Haluzik, an endocrinologist and professor at Charles University in Prague.
Two phase 2 studies of LY3437943 are underway and are scheduled to finish before the end of 2022. They include a study of about 300 people with type 2 diabetes that’s running at 43 U.S. sites, and a second study of about 500 people with overweight or obesity running at 28 U.S. sites.
The study was sponsored by Eli Lilly, the company developing LY3437943. Dr. Milicevic is an employee of and stockholder of Eli Lilly. Dr. Haluzik has been an adviser to, consultant to, and received honoraria and research support from Eli Lilly. He has had similar relationships with Amgen, AstraZeneca, Boehringer Ingelheim, BristolMyersSquibb, Janssen, Johnson & Johnson, Mundipharma, Novo Nordisk, and Sanofi.
STOCKHOLM – First came the GLP-1 receptor agonists as treatments for patients with type 2 diabetes, then came tirzepatide (Mounjaro) which added a second incretin agonism for the receptor to the glucose-dependent insulinotropic polypeptide (GIP). Now coming onto the clinical scene is a molecule with triple agonism to the GLP-1 receptor, the GIP receptor, and to the glucagon receptor.
That molecule, LY3437943, showed reasonable safety and tolerability and an apparent incremental uptick in weight loss compared with the approved incretin-based agents for people with type 2 diabetes in a 12-week, dose-ranging study involving a 52 patients with type 2 diabetes who received the new agent.
The 12 people who uptitrated for a total of 12 weeks and reached the highest tested dose of LY3437943, 12 mg, injected once weekly during the final 4 weeks, showed an average weight loss of 8.65 kg, while the 11 patients who maxed out at a weekly dose of 6 mg of LY3437943 had an average 12-week weight loss of 7.52 kg, Zvonko Milicevic, MD, reported at the annual meeting of the European Association for the Study of Diabetes.
Fifteen more participants received placebo and five received a comparator GLP-1 receptor agonist. All 72 patients in the study were also already on treatment with metformin when they entered, and they were maintained on metformin throughout the study period.
The new agent showed “greater weight loss efficacy than currently approved medications,” said Dr. Milicevic, a staff researcher who works in Vienna for Eli Lilly, the company developing LY3437943.
‘Really impressive’ weight loss
Martin Haluzik, MD, who chaired the session where Dr. Milicevic spoke, agreed. “The data, especially for weight reduction, were really impressive,” Dr. Haluzik said in an interview. “It looks stronger than the best we have at the moment,” the dual incretin agonist tirzepatide, he added.
Cross-study comparisons are very unreliable, but to put the weight loss seen with LY3437943 in perspective, the 12-week weight reduction that occurred with the highest dose of tirzepatide tested (15 mg/weekly) in the pivotal SURPASS-2 trial with 1,879 randomized patients with type 2 diabetes was an average of roughly 5 kg, while the comparator of 1 mg weekly of semaglutide (Ozempic) tested in the same study produced an average weight loss of about 4 kg.
Other notable efficacy results for LY3437943 after 12 weeks on treatment included an average reduction in hemoglobin A1c from baseline of 1.90%, achieved in the group that received 6 mg weekly as their maximum dose for 8 weeks after a 4-week run-in at a lower dose; a reduction in systolic blood pressure of 7.99 mm Hg on the 6-mg maximum weekly dose and of 12.06 mm Hg on the maximum 12-mg weekly dose; and “robust” reductions in lipids including cuts from baseline of about 40% for both triglycerides and very-LDL cholesterol, Dr. Milicevic reported.
Adverse effects resemble approved incretin-based agents
The study, which ran at four U.S. sites, had a primary objective of safety assessment, and Dr. Milicevic said the results showed acceptable safety and tolerability consistent with the glucagon-like peptide-1 (GLP-1) receptor agonists and tirzepatide. Like those agents, LY3437943 caused primarily mild gastrointestinal adverse effects such as nausea and diarrhea. Of the 52 patients in the study who received the triple agonist, 4 discontinued treatment because of a treatment-emergent adverse effect, including 1 patient in the subgroup who received the maximum dose.
The only concerning adverse effect noted by Dr. Haluzik was the average increase in heart rate from baseline of 10.26 beats/min in the subgroup that received the maximum dose, roughly twice the increase seen with tirzepatide and semaglutide in SURPASS-2. The average heart rate increase was about half that, 5.30 beats/min compared with baseline, in the subgroup that received a maximum weekly dose of 6 mg.
Overall, the results showed “no major adverse effects that might hamper use,” said Dr. Haluzik, an endocrinologist and professor at Charles University in Prague.
Two phase 2 studies of LY3437943 are underway and are scheduled to finish before the end of 2022. They include a study of about 300 people with type 2 diabetes that’s running at 43 U.S. sites, and a second study of about 500 people with overweight or obesity running at 28 U.S. sites.
The study was sponsored by Eli Lilly, the company developing LY3437943. Dr. Milicevic is an employee of and stockholder of Eli Lilly. Dr. Haluzik has been an adviser to, consultant to, and received honoraria and research support from Eli Lilly. He has had similar relationships with Amgen, AstraZeneca, Boehringer Ingelheim, BristolMyersSquibb, Janssen, Johnson & Johnson, Mundipharma, Novo Nordisk, and Sanofi.
STOCKHOLM – First came the GLP-1 receptor agonists as treatments for patients with type 2 diabetes, then came tirzepatide (Mounjaro) which added a second incretin agonism for the receptor to the glucose-dependent insulinotropic polypeptide (GIP). Now coming onto the clinical scene is a molecule with triple agonism to the GLP-1 receptor, the GIP receptor, and to the glucagon receptor.
That molecule, LY3437943, showed reasonable safety and tolerability and an apparent incremental uptick in weight loss compared with the approved incretin-based agents for people with type 2 diabetes in a 12-week, dose-ranging study involving a 52 patients with type 2 diabetes who received the new agent.
The 12 people who uptitrated for a total of 12 weeks and reached the highest tested dose of LY3437943, 12 mg, injected once weekly during the final 4 weeks, showed an average weight loss of 8.65 kg, while the 11 patients who maxed out at a weekly dose of 6 mg of LY3437943 had an average 12-week weight loss of 7.52 kg, Zvonko Milicevic, MD, reported at the annual meeting of the European Association for the Study of Diabetes.
Fifteen more participants received placebo and five received a comparator GLP-1 receptor agonist. All 72 patients in the study were also already on treatment with metformin when they entered, and they were maintained on metformin throughout the study period.
The new agent showed “greater weight loss efficacy than currently approved medications,” said Dr. Milicevic, a staff researcher who works in Vienna for Eli Lilly, the company developing LY3437943.
‘Really impressive’ weight loss
Martin Haluzik, MD, who chaired the session where Dr. Milicevic spoke, agreed. “The data, especially for weight reduction, were really impressive,” Dr. Haluzik said in an interview. “It looks stronger than the best we have at the moment,” the dual incretin agonist tirzepatide, he added.
Cross-study comparisons are very unreliable, but to put the weight loss seen with LY3437943 in perspective, the 12-week weight reduction that occurred with the highest dose of tirzepatide tested (15 mg/weekly) in the pivotal SURPASS-2 trial with 1,879 randomized patients with type 2 diabetes was an average of roughly 5 kg, while the comparator of 1 mg weekly of semaglutide (Ozempic) tested in the same study produced an average weight loss of about 4 kg.
Other notable efficacy results for LY3437943 after 12 weeks on treatment included an average reduction in hemoglobin A1c from baseline of 1.90%, achieved in the group that received 6 mg weekly as their maximum dose for 8 weeks after a 4-week run-in at a lower dose; a reduction in systolic blood pressure of 7.99 mm Hg on the 6-mg maximum weekly dose and of 12.06 mm Hg on the maximum 12-mg weekly dose; and “robust” reductions in lipids including cuts from baseline of about 40% for both triglycerides and very-LDL cholesterol, Dr. Milicevic reported.
Adverse effects resemble approved incretin-based agents
The study, which ran at four U.S. sites, had a primary objective of safety assessment, and Dr. Milicevic said the results showed acceptable safety and tolerability consistent with the glucagon-like peptide-1 (GLP-1) receptor agonists and tirzepatide. Like those agents, LY3437943 caused primarily mild gastrointestinal adverse effects such as nausea and diarrhea. Of the 52 patients in the study who received the triple agonist, 4 discontinued treatment because of a treatment-emergent adverse effect, including 1 patient in the subgroup who received the maximum dose.
The only concerning adverse effect noted by Dr. Haluzik was the average increase in heart rate from baseline of 10.26 beats/min in the subgroup that received the maximum dose, roughly twice the increase seen with tirzepatide and semaglutide in SURPASS-2. The average heart rate increase was about half that, 5.30 beats/min compared with baseline, in the subgroup that received a maximum weekly dose of 6 mg.
Overall, the results showed “no major adverse effects that might hamper use,” said Dr. Haluzik, an endocrinologist and professor at Charles University in Prague.
Two phase 2 studies of LY3437943 are underway and are scheduled to finish before the end of 2022. They include a study of about 300 people with type 2 diabetes that’s running at 43 U.S. sites, and a second study of about 500 people with overweight or obesity running at 28 U.S. sites.
The study was sponsored by Eli Lilly, the company developing LY3437943. Dr. Milicevic is an employee of and stockholder of Eli Lilly. Dr. Haluzik has been an adviser to, consultant to, and received honoraria and research support from Eli Lilly. He has had similar relationships with Amgen, AstraZeneca, Boehringer Ingelheim, BristolMyersSquibb, Janssen, Johnson & Johnson, Mundipharma, Novo Nordisk, and Sanofi.
AT EASD 2022
‘Amazing’ data for cheap beta-blocker gel for diabetic foot ulcers
STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.
Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.
Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.
“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.
Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.
However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).
Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.
“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.
“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
Study across 27 sites in India
Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care. Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.
Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m2 and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm2, two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.
After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).
Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.
The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.
The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.
Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.
Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
50% more patients on esmolol had complete ulcer closure
The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).
“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).
Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).
The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.
In wounds less than 5 cm2, the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm2, these proportions were 47.6% vs. 26.9%.
Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.
Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.
Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
A class effect of beta blockers?
The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).
Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.
“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.
Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.
Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.
Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.
“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.
Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.
However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).
Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.
“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.
“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
Study across 27 sites in India
Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care. Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.
Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m2 and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm2, two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.
After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).
Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.
The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.
The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.
Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.
Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
50% more patients on esmolol had complete ulcer closure
The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).
“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).
Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).
The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.
In wounds less than 5 cm2, the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm2, these proportions were 47.6% vs. 26.9%.
Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.
Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.
Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
A class effect of beta blockers?
The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).
Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.
“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.
Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.
Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.
Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.
“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.
Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.
However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).
Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.
“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.
“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
Study across 27 sites in India
Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care. Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.
Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m2 and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm2, two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.
After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).
Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.
The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.
The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.
Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.
Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
50% more patients on esmolol had complete ulcer closure
The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).
“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).
Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).
The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.
In wounds less than 5 cm2, the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm2, these proportions were 47.6% vs. 26.9%.
Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.
Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.
Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
A class effect of beta blockers?
The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).
Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.
“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.
Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EASD 2022
Eat more dairy, less red meat to prevent type 2 diabetes
STOCKHOLM – Among animal protein foods, low-fat dairy consumption may minimize the risk of developing type 2 diabetes while red meat raises that risk, a new analysis finds.
“A plant-based dietary pattern with limited intake of meat, moderate intake of fish, eggs, and full-fat dairy, and habitual consumption of yogurt, milk, or low-fat dairy, might represent the most feasible, sustainable, and successful population strategy to optimize the prevention of type 2 diabetes,” lead author Annalisa Giosuè, MD, of the University of Naples (Italy) Federico II, told this news organization.
She presented the findings from an umbrella review of 13 dose-response meta-analyses of prospective cohort studies at the annual meeting of the European Association for the Study of Diabetes.
The study is believed to be the first comprehensive overview of the available evidence from all published meta-analyses on the relationship between well-defined amounts of animal-origin foods and the risk of type 2 diabetes.
Dr. Giosuè and colleagues focused on animal-based foods because they represent a gap in most guidelines for type 2 diabetes prevention, she explained.
“The existing evidence and dietary recommendations for type 2 diabetes prevention are mainly based on the appropriate consumption of plant foods: high amounts of the fiber-rich ones and low consumption of the refined ones as well as those rich in free sugars. And also on the adequate choice among fat sources – reduction of saturated fat sources like butter and cream and replacement with plant-based poly- and monounsaturated fat sources like nontropical vegetable oils. But not on the most suitable choices among different animal foods for the prevention of type 2 diabetes,” she explained.
The new findings are in line with the Mediterranean diet in that, while plant based, it also limits red-meat consumption, but not all animal-based foods, and has consistently been associated with a reduced risk of type 2 diabetes. Vegetarian diets have also been associated with a reduced risk of type 2 diabetes, but far less evidence is available for that, she said.
Asked for comment, session moderator Matthias Schulze, MD, head of the department of molecular epidemiology at the German Institute of Human Nutrition, Berlin, said: “Decreasing intake of red and processed meat is already a strong recommendation, and these data support that. You have to make choices for and against [certain] foods. So, if you decide to eat less red meat, then the question is what do you eat instead? This study shows that specifically other animal products, like dairy and ... fish or white meat sources ... are healthy among the animal-based foods. But you could also obviously look at plant-based foods as protein sources as well.”
And Dr. Schulze noted that the data suggest another dimension to type 2 diabetes prevention beyond simply focusing on weight loss.
“You can achieve weight loss with very different diets. Diet quality plays an important role. These data support that if you look at diabetes prevention, then you would focus on people with high intakes of specific animal-based foods, besides looking at overweight and obesity. Then you could intervene to reduce this intake, with potential substitutions with other animal foods like fish or white meat, or plant-based sources of proteins.”
Red meat damages, dairy protects
The 13 meta-analyses included 175 summary risk ratios for type 2 diabetes incidence for the consumption of total meat, red meat, white meat, processed meats, fish, total dairy, full-fat dairy, low-fat dairy, milk, cheese, yogurt, or eggs.
Significant increases in the risk of developing type 2 diabetes were found for consumption of 100 g/day of total meat (SRR, 1.20; 20% increase) and red meat (SRR, 1.22, 22% increase) and with 50 g/day of processed meats (SRR, 1.30; 30% increase). A borderline increased risk was also seen for 50 g/day of white meat (SRR, 1.04; 4% increase).
The opposite was found for dairy foods. Inverse associations for type 2 diabetes development were found for an intake of 200 g/day of total dairy (SRR, 0.95; 5% reduction), low-fat dairy (SRR, 0.96; 4% reduction), milk (SRR, 0.90; 10% reduction), and for 100 g/day of yogurt (SRR, 0.94, 6% reduction).
Neutral (nonsignificant) effects were found for 200 g/day of full-fat dairy (SRR, 0.98) and for 30 g/day of cheese (SRR, 0.97). Fish consumption also had a neutral association with type 2 diabetes risk (SRR, 1.04 for 100 g/day) as did one egg per day (SRR, 1.07), but evidence quality was low.
And, Dr. Giosuè noted during her presentation, these relationships could change with alterations in the amounts consumed.
Dr. Schulze commented: “Fish is more clearly related to reduced cardiovascular risk than for preventing type 2 diabetes, where we’ve had mixed results. They might not always be the same.”
What are the mechanisms?
The reasons for these positive and negative associations aren’t entirely clear, but Dr. Giosuè noted that dairy products contain several nutrients, vitamins, and other components, such as calcium and vitamin D, that have potential beneficial effects on glucose metabolism.
In particular, she said, “Whey proteins in milk have a well-known beneficial effect on the regulation of the rise of glucose levels in the blood after meals, and also on the control of appetite and body weight.”
Moreover, probiotics found in yogurt have been linked to protective effects against weight gain and obesity, which “may in part [explain] the beneficial role of yogurt in type 2 diabetes prevention.”
Meat, in contrast, is full of cholesterol, saturated fatty acids, and heme iron, which can promote subclinical inflammation and oxidative stress, which may in turn, affect insulin sensitivity, Dr. Giosuè explained. What’s more, “processed meats also contain nitrates, nitrites, and sodium that can contribute to pancreatic cell damage and vascular dysfunction, thus affecting insulin sensitivity.”
And white meat (poultry) has a lower fat content than red meats such as beef, lamb, and pork, as well as a more favorable fatty acid profile and a lower heme-iron content, she said in an interview.
What about vegan diets? The devil is in the details
Asked about the relative health benefits of diets that completely eliminate animal-based foods, Dr. Giosuè replied: “What is important to keep in mind when hearing about the potential of vegan diets to prevent, or manage, or induce the remission of type 2 diabetes, is that the inclusion in the diet of solely foods of plant origin does not mean ‘automatically’ to eat only foods that are good for diabetes prevention.”
“Just like the exclusion of all foods of animal origin is not equivalent to reduce the risk of type 2 diabetes ... Solid evidence has demonstrated that plant foods which are refined and/or rich in free sugars like white bread, biscuits, and sweetened beverages are as harmful as red and processed meats for diabetes incidence and progression.”
Dr. Giosuè and Dr. Schulze have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Among animal protein foods, low-fat dairy consumption may minimize the risk of developing type 2 diabetes while red meat raises that risk, a new analysis finds.
“A plant-based dietary pattern with limited intake of meat, moderate intake of fish, eggs, and full-fat dairy, and habitual consumption of yogurt, milk, or low-fat dairy, might represent the most feasible, sustainable, and successful population strategy to optimize the prevention of type 2 diabetes,” lead author Annalisa Giosuè, MD, of the University of Naples (Italy) Federico II, told this news organization.
She presented the findings from an umbrella review of 13 dose-response meta-analyses of prospective cohort studies at the annual meeting of the European Association for the Study of Diabetes.
The study is believed to be the first comprehensive overview of the available evidence from all published meta-analyses on the relationship between well-defined amounts of animal-origin foods and the risk of type 2 diabetes.
Dr. Giosuè and colleagues focused on animal-based foods because they represent a gap in most guidelines for type 2 diabetes prevention, she explained.
“The existing evidence and dietary recommendations for type 2 diabetes prevention are mainly based on the appropriate consumption of plant foods: high amounts of the fiber-rich ones and low consumption of the refined ones as well as those rich in free sugars. And also on the adequate choice among fat sources – reduction of saturated fat sources like butter and cream and replacement with plant-based poly- and monounsaturated fat sources like nontropical vegetable oils. But not on the most suitable choices among different animal foods for the prevention of type 2 diabetes,” she explained.
The new findings are in line with the Mediterranean diet in that, while plant based, it also limits red-meat consumption, but not all animal-based foods, and has consistently been associated with a reduced risk of type 2 diabetes. Vegetarian diets have also been associated with a reduced risk of type 2 diabetes, but far less evidence is available for that, she said.
Asked for comment, session moderator Matthias Schulze, MD, head of the department of molecular epidemiology at the German Institute of Human Nutrition, Berlin, said: “Decreasing intake of red and processed meat is already a strong recommendation, and these data support that. You have to make choices for and against [certain] foods. So, if you decide to eat less red meat, then the question is what do you eat instead? This study shows that specifically other animal products, like dairy and ... fish or white meat sources ... are healthy among the animal-based foods. But you could also obviously look at plant-based foods as protein sources as well.”
And Dr. Schulze noted that the data suggest another dimension to type 2 diabetes prevention beyond simply focusing on weight loss.
“You can achieve weight loss with very different diets. Diet quality plays an important role. These data support that if you look at diabetes prevention, then you would focus on people with high intakes of specific animal-based foods, besides looking at overweight and obesity. Then you could intervene to reduce this intake, with potential substitutions with other animal foods like fish or white meat, or plant-based sources of proteins.”
Red meat damages, dairy protects
The 13 meta-analyses included 175 summary risk ratios for type 2 diabetes incidence for the consumption of total meat, red meat, white meat, processed meats, fish, total dairy, full-fat dairy, low-fat dairy, milk, cheese, yogurt, or eggs.
Significant increases in the risk of developing type 2 diabetes were found for consumption of 100 g/day of total meat (SRR, 1.20; 20% increase) and red meat (SRR, 1.22, 22% increase) and with 50 g/day of processed meats (SRR, 1.30; 30% increase). A borderline increased risk was also seen for 50 g/day of white meat (SRR, 1.04; 4% increase).
The opposite was found for dairy foods. Inverse associations for type 2 diabetes development were found for an intake of 200 g/day of total dairy (SRR, 0.95; 5% reduction), low-fat dairy (SRR, 0.96; 4% reduction), milk (SRR, 0.90; 10% reduction), and for 100 g/day of yogurt (SRR, 0.94, 6% reduction).
Neutral (nonsignificant) effects were found for 200 g/day of full-fat dairy (SRR, 0.98) and for 30 g/day of cheese (SRR, 0.97). Fish consumption also had a neutral association with type 2 diabetes risk (SRR, 1.04 for 100 g/day) as did one egg per day (SRR, 1.07), but evidence quality was low.
And, Dr. Giosuè noted during her presentation, these relationships could change with alterations in the amounts consumed.
Dr. Schulze commented: “Fish is more clearly related to reduced cardiovascular risk than for preventing type 2 diabetes, where we’ve had mixed results. They might not always be the same.”
What are the mechanisms?
The reasons for these positive and negative associations aren’t entirely clear, but Dr. Giosuè noted that dairy products contain several nutrients, vitamins, and other components, such as calcium and vitamin D, that have potential beneficial effects on glucose metabolism.
In particular, she said, “Whey proteins in milk have a well-known beneficial effect on the regulation of the rise of glucose levels in the blood after meals, and also on the control of appetite and body weight.”
Moreover, probiotics found in yogurt have been linked to protective effects against weight gain and obesity, which “may in part [explain] the beneficial role of yogurt in type 2 diabetes prevention.”
Meat, in contrast, is full of cholesterol, saturated fatty acids, and heme iron, which can promote subclinical inflammation and oxidative stress, which may in turn, affect insulin sensitivity, Dr. Giosuè explained. What’s more, “processed meats also contain nitrates, nitrites, and sodium that can contribute to pancreatic cell damage and vascular dysfunction, thus affecting insulin sensitivity.”
And white meat (poultry) has a lower fat content than red meats such as beef, lamb, and pork, as well as a more favorable fatty acid profile and a lower heme-iron content, she said in an interview.
What about vegan diets? The devil is in the details
Asked about the relative health benefits of diets that completely eliminate animal-based foods, Dr. Giosuè replied: “What is important to keep in mind when hearing about the potential of vegan diets to prevent, or manage, or induce the remission of type 2 diabetes, is that the inclusion in the diet of solely foods of plant origin does not mean ‘automatically’ to eat only foods that are good for diabetes prevention.”
“Just like the exclusion of all foods of animal origin is not equivalent to reduce the risk of type 2 diabetes ... Solid evidence has demonstrated that plant foods which are refined and/or rich in free sugars like white bread, biscuits, and sweetened beverages are as harmful as red and processed meats for diabetes incidence and progression.”
Dr. Giosuè and Dr. Schulze have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Among animal protein foods, low-fat dairy consumption may minimize the risk of developing type 2 diabetes while red meat raises that risk, a new analysis finds.
“A plant-based dietary pattern with limited intake of meat, moderate intake of fish, eggs, and full-fat dairy, and habitual consumption of yogurt, milk, or low-fat dairy, might represent the most feasible, sustainable, and successful population strategy to optimize the prevention of type 2 diabetes,” lead author Annalisa Giosuè, MD, of the University of Naples (Italy) Federico II, told this news organization.
She presented the findings from an umbrella review of 13 dose-response meta-analyses of prospective cohort studies at the annual meeting of the European Association for the Study of Diabetes.
The study is believed to be the first comprehensive overview of the available evidence from all published meta-analyses on the relationship between well-defined amounts of animal-origin foods and the risk of type 2 diabetes.
Dr. Giosuè and colleagues focused on animal-based foods because they represent a gap in most guidelines for type 2 diabetes prevention, she explained.
“The existing evidence and dietary recommendations for type 2 diabetes prevention are mainly based on the appropriate consumption of plant foods: high amounts of the fiber-rich ones and low consumption of the refined ones as well as those rich in free sugars. And also on the adequate choice among fat sources – reduction of saturated fat sources like butter and cream and replacement with plant-based poly- and monounsaturated fat sources like nontropical vegetable oils. But not on the most suitable choices among different animal foods for the prevention of type 2 diabetes,” she explained.
The new findings are in line with the Mediterranean diet in that, while plant based, it also limits red-meat consumption, but not all animal-based foods, and has consistently been associated with a reduced risk of type 2 diabetes. Vegetarian diets have also been associated with a reduced risk of type 2 diabetes, but far less evidence is available for that, she said.
Asked for comment, session moderator Matthias Schulze, MD, head of the department of molecular epidemiology at the German Institute of Human Nutrition, Berlin, said: “Decreasing intake of red and processed meat is already a strong recommendation, and these data support that. You have to make choices for and against [certain] foods. So, if you decide to eat less red meat, then the question is what do you eat instead? This study shows that specifically other animal products, like dairy and ... fish or white meat sources ... are healthy among the animal-based foods. But you could also obviously look at plant-based foods as protein sources as well.”
And Dr. Schulze noted that the data suggest another dimension to type 2 diabetes prevention beyond simply focusing on weight loss.
“You can achieve weight loss with very different diets. Diet quality plays an important role. These data support that if you look at diabetes prevention, then you would focus on people with high intakes of specific animal-based foods, besides looking at overweight and obesity. Then you could intervene to reduce this intake, with potential substitutions with other animal foods like fish or white meat, or plant-based sources of proteins.”
Red meat damages, dairy protects
The 13 meta-analyses included 175 summary risk ratios for type 2 diabetes incidence for the consumption of total meat, red meat, white meat, processed meats, fish, total dairy, full-fat dairy, low-fat dairy, milk, cheese, yogurt, or eggs.
Significant increases in the risk of developing type 2 diabetes were found for consumption of 100 g/day of total meat (SRR, 1.20; 20% increase) and red meat (SRR, 1.22, 22% increase) and with 50 g/day of processed meats (SRR, 1.30; 30% increase). A borderline increased risk was also seen for 50 g/day of white meat (SRR, 1.04; 4% increase).
The opposite was found for dairy foods. Inverse associations for type 2 diabetes development were found for an intake of 200 g/day of total dairy (SRR, 0.95; 5% reduction), low-fat dairy (SRR, 0.96; 4% reduction), milk (SRR, 0.90; 10% reduction), and for 100 g/day of yogurt (SRR, 0.94, 6% reduction).
Neutral (nonsignificant) effects were found for 200 g/day of full-fat dairy (SRR, 0.98) and for 30 g/day of cheese (SRR, 0.97). Fish consumption also had a neutral association with type 2 diabetes risk (SRR, 1.04 for 100 g/day) as did one egg per day (SRR, 1.07), but evidence quality was low.
And, Dr. Giosuè noted during her presentation, these relationships could change with alterations in the amounts consumed.
Dr. Schulze commented: “Fish is more clearly related to reduced cardiovascular risk than for preventing type 2 diabetes, where we’ve had mixed results. They might not always be the same.”
What are the mechanisms?
The reasons for these positive and negative associations aren’t entirely clear, but Dr. Giosuè noted that dairy products contain several nutrients, vitamins, and other components, such as calcium and vitamin D, that have potential beneficial effects on glucose metabolism.
In particular, she said, “Whey proteins in milk have a well-known beneficial effect on the regulation of the rise of glucose levels in the blood after meals, and also on the control of appetite and body weight.”
Moreover, probiotics found in yogurt have been linked to protective effects against weight gain and obesity, which “may in part [explain] the beneficial role of yogurt in type 2 diabetes prevention.”
Meat, in contrast, is full of cholesterol, saturated fatty acids, and heme iron, which can promote subclinical inflammation and oxidative stress, which may in turn, affect insulin sensitivity, Dr. Giosuè explained. What’s more, “processed meats also contain nitrates, nitrites, and sodium that can contribute to pancreatic cell damage and vascular dysfunction, thus affecting insulin sensitivity.”
And white meat (poultry) has a lower fat content than red meats such as beef, lamb, and pork, as well as a more favorable fatty acid profile and a lower heme-iron content, she said in an interview.
What about vegan diets? The devil is in the details
Asked about the relative health benefits of diets that completely eliminate animal-based foods, Dr. Giosuè replied: “What is important to keep in mind when hearing about the potential of vegan diets to prevent, or manage, or induce the remission of type 2 diabetes, is that the inclusion in the diet of solely foods of plant origin does not mean ‘automatically’ to eat only foods that are good for diabetes prevention.”
“Just like the exclusion of all foods of animal origin is not equivalent to reduce the risk of type 2 diabetes ... Solid evidence has demonstrated that plant foods which are refined and/or rich in free sugars like white bread, biscuits, and sweetened beverages are as harmful as red and processed meats for diabetes incidence and progression.”
Dr. Giosuè and Dr. Schulze have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT EASD 2022
Whole grains may improve survival in people with type 2 diabetes
STOCKHOLM – Higher consumption of whole grains, fish, fiber, and omega-3 polyunsaturated fatty acids reduces deaths from all causes in people with type 2 diabetes, show new data.
Results from the systematic review and meta-analysis were presented at the annual meeting of the European Association for the Study of Diabetes by lead author Janett Barbaresko, PhD, a researcher from the German Diabetes Center in Düsseldorf.
Adding just one serving (around 20 g/day) of whole grains from foods such as brown bread, brown rice, or breakfast cereals was associated with about a 16% reduction in all-cause mortality, and each portion of fish consumed per week was associated with a 5% lower risk of all-cause mortality. In addition, eating 5 g/day of fiber was associated with a 14% reduction in all-cause mortality, and 0.1 g/day of omega-3 polyunsaturated fatty acids with a 13% reduction.
Diet also has role in improving survival in those with type 2 diabetes
Dr. Barbaresko explained that most dietary recommendations for people with type 2 diabetes are not evidence based or are derived from studies of the general population, and that the degree to which different components of diet are associated with all-cause mortality, or indeed the prevention of morbidity and mortality, remains unknown.
By way of example, she noted the American Diabetes Association 2022 guidelines for the prevention and management of diabetes complications advises limited intake of saturated and trans fatty acids, higher intake of polyunsaturated fatty acids, and following the Mediterranean or DASH (Dietary Approaches to Stop Hypertension) diets.
“Our findings show that dietary factors not only play a role in the prevention of type 2 diabetes, but also seem to be relevant for improving survival in people with diagnosed diabetes,” she said, adding that, “in particular, we found some key aspects of a healthy diet such as higher intakes of whole grains, fiber, fish, and omega-3 polyunsaturated fatty acids may improve survival of individuals with type 2 diabetes.”
She noted that individuals with type 2 diabetes are known to be more prone to circulatory diseases, dementia, cancer, and bone fractures, and that lifestyle modifications, including diet – with or without medications – underpin most management strategies.
“For the first time, we have provided a summary of all published studies on any dietary factor in association to all-cause mortality in individuals with type 2 diabetes,” said Dr. Barbaresko. “Moreover, the certainty of evidence has been evaluated for the first time.”
Matthias Schulze, MD, head of the German Institute of Human Nutrition, Berlin, moderated the session.
The new work “summarizes the available evidence, providing important dietary advice for patients with diabetes, for example, recommending whole grains,” he remarked. “However, the study also points to gaps in knowledge, so for many diet factors, we have either no or few studies, or study quality considered to be low, which calls for more research to fill the gap.”
High versus low intake of various dietary factors
The researchers performed meta-analyses based on published studies of all-cause mortality in individuals with type 2 diabetes aged 18 years and over, as associated with dietary patterns, macronutrients (carbohydrates, protein, fat), micronutrients (vitamins and minerals), secondary plant compounds (for example, polyphenols), and supplements.
Studies were conducted mainly in the United States and Europe with a mean follow-up of 10 years. Low and high intake were compared, and a dose-response relationship between different dietary factors and all-cause mortality was explored to generate summary risk ratios. The researchers also explored how the certainty of evidence was determined.
Decreased mortality from any cause was found for a higher intake of fish (SRR per serving/week, 0.95; over six studies); whole grain (SRR per 20 g/day, 0.84; two studies); fiber (SRR per 5 g/day, 0.86; three studies), and omega-3 polyunsaturated fatty acids (SRR per 0.1 g/day, 0.87; two studies).
A low certainty of evidence was found for an inverse association between all-cause mortality and vegetable consumption (SRR per 100 g/day, 0.88; two studies) and plant protein intake (SRR per 10 g/day, 0.91; three studies).
Eggs were associated with an increased risk of all-cause mortality (SRR per 10 g/day, 1.05; seven studies), as was dietary cholesterol (SRR per 300 mg/day, 1.19; two studies).
Regarding other dietary patterns, including the Mediterranean diet and low-carbohydrate diet, either no association was found and/or the evidence was very uncertain. Likewise, evidence was uncertain for foods including nuts, dairy, meat, sugar and sweets; macronutrients, including carbohydrates; and micronutrients, such as caffeine and vitamin D.
“With the Mediterranean diet, we saw an inverse association [with all-cause mortality] comparing high adherence with low adherence to the Mediterranean diet, but the certainty of evidence was very low, indicating a really uncertain meta-evidence,” remarked Dr. Barbaresko.
She concluded that a greater number of studies is needed to investigate the association of dietary factors with all-cause mortality in type 2 diabetes to strengthen the evidence for several other dietary factors. She also cautioned that meta-analyses are affected by unmeasured and residual confounding.
Dr. Barbaresko and Dr. Schulze reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Higher consumption of whole grains, fish, fiber, and omega-3 polyunsaturated fatty acids reduces deaths from all causes in people with type 2 diabetes, show new data.
Results from the systematic review and meta-analysis were presented at the annual meeting of the European Association for the Study of Diabetes by lead author Janett Barbaresko, PhD, a researcher from the German Diabetes Center in Düsseldorf.
Adding just one serving (around 20 g/day) of whole grains from foods such as brown bread, brown rice, or breakfast cereals was associated with about a 16% reduction in all-cause mortality, and each portion of fish consumed per week was associated with a 5% lower risk of all-cause mortality. In addition, eating 5 g/day of fiber was associated with a 14% reduction in all-cause mortality, and 0.1 g/day of omega-3 polyunsaturated fatty acids with a 13% reduction.
Diet also has role in improving survival in those with type 2 diabetes
Dr. Barbaresko explained that most dietary recommendations for people with type 2 diabetes are not evidence based or are derived from studies of the general population, and that the degree to which different components of diet are associated with all-cause mortality, or indeed the prevention of morbidity and mortality, remains unknown.
By way of example, she noted the American Diabetes Association 2022 guidelines for the prevention and management of diabetes complications advises limited intake of saturated and trans fatty acids, higher intake of polyunsaturated fatty acids, and following the Mediterranean or DASH (Dietary Approaches to Stop Hypertension) diets.
“Our findings show that dietary factors not only play a role in the prevention of type 2 diabetes, but also seem to be relevant for improving survival in people with diagnosed diabetes,” she said, adding that, “in particular, we found some key aspects of a healthy diet such as higher intakes of whole grains, fiber, fish, and omega-3 polyunsaturated fatty acids may improve survival of individuals with type 2 diabetes.”
She noted that individuals with type 2 diabetes are known to be more prone to circulatory diseases, dementia, cancer, and bone fractures, and that lifestyle modifications, including diet – with or without medications – underpin most management strategies.
“For the first time, we have provided a summary of all published studies on any dietary factor in association to all-cause mortality in individuals with type 2 diabetes,” said Dr. Barbaresko. “Moreover, the certainty of evidence has been evaluated for the first time.”
Matthias Schulze, MD, head of the German Institute of Human Nutrition, Berlin, moderated the session.
The new work “summarizes the available evidence, providing important dietary advice for patients with diabetes, for example, recommending whole grains,” he remarked. “However, the study also points to gaps in knowledge, so for many diet factors, we have either no or few studies, or study quality considered to be low, which calls for more research to fill the gap.”
High versus low intake of various dietary factors
The researchers performed meta-analyses based on published studies of all-cause mortality in individuals with type 2 diabetes aged 18 years and over, as associated with dietary patterns, macronutrients (carbohydrates, protein, fat), micronutrients (vitamins and minerals), secondary plant compounds (for example, polyphenols), and supplements.
Studies were conducted mainly in the United States and Europe with a mean follow-up of 10 years. Low and high intake were compared, and a dose-response relationship between different dietary factors and all-cause mortality was explored to generate summary risk ratios. The researchers also explored how the certainty of evidence was determined.
Decreased mortality from any cause was found for a higher intake of fish (SRR per serving/week, 0.95; over six studies); whole grain (SRR per 20 g/day, 0.84; two studies); fiber (SRR per 5 g/day, 0.86; three studies), and omega-3 polyunsaturated fatty acids (SRR per 0.1 g/day, 0.87; two studies).
A low certainty of evidence was found for an inverse association between all-cause mortality and vegetable consumption (SRR per 100 g/day, 0.88; two studies) and plant protein intake (SRR per 10 g/day, 0.91; three studies).
Eggs were associated with an increased risk of all-cause mortality (SRR per 10 g/day, 1.05; seven studies), as was dietary cholesterol (SRR per 300 mg/day, 1.19; two studies).
Regarding other dietary patterns, including the Mediterranean diet and low-carbohydrate diet, either no association was found and/or the evidence was very uncertain. Likewise, evidence was uncertain for foods including nuts, dairy, meat, sugar and sweets; macronutrients, including carbohydrates; and micronutrients, such as caffeine and vitamin D.
“With the Mediterranean diet, we saw an inverse association [with all-cause mortality] comparing high adherence with low adherence to the Mediterranean diet, but the certainty of evidence was very low, indicating a really uncertain meta-evidence,” remarked Dr. Barbaresko.
She concluded that a greater number of studies is needed to investigate the association of dietary factors with all-cause mortality in type 2 diabetes to strengthen the evidence for several other dietary factors. She also cautioned that meta-analyses are affected by unmeasured and residual confounding.
Dr. Barbaresko and Dr. Schulze reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Higher consumption of whole grains, fish, fiber, and omega-3 polyunsaturated fatty acids reduces deaths from all causes in people with type 2 diabetes, show new data.
Results from the systematic review and meta-analysis were presented at the annual meeting of the European Association for the Study of Diabetes by lead author Janett Barbaresko, PhD, a researcher from the German Diabetes Center in Düsseldorf.
Adding just one serving (around 20 g/day) of whole grains from foods such as brown bread, brown rice, or breakfast cereals was associated with about a 16% reduction in all-cause mortality, and each portion of fish consumed per week was associated with a 5% lower risk of all-cause mortality. In addition, eating 5 g/day of fiber was associated with a 14% reduction in all-cause mortality, and 0.1 g/day of omega-3 polyunsaturated fatty acids with a 13% reduction.
Diet also has role in improving survival in those with type 2 diabetes
Dr. Barbaresko explained that most dietary recommendations for people with type 2 diabetes are not evidence based or are derived from studies of the general population, and that the degree to which different components of diet are associated with all-cause mortality, or indeed the prevention of morbidity and mortality, remains unknown.
By way of example, she noted the American Diabetes Association 2022 guidelines for the prevention and management of diabetes complications advises limited intake of saturated and trans fatty acids, higher intake of polyunsaturated fatty acids, and following the Mediterranean or DASH (Dietary Approaches to Stop Hypertension) diets.
“Our findings show that dietary factors not only play a role in the prevention of type 2 diabetes, but also seem to be relevant for improving survival in people with diagnosed diabetes,” she said, adding that, “in particular, we found some key aspects of a healthy diet such as higher intakes of whole grains, fiber, fish, and omega-3 polyunsaturated fatty acids may improve survival of individuals with type 2 diabetes.”
She noted that individuals with type 2 diabetes are known to be more prone to circulatory diseases, dementia, cancer, and bone fractures, and that lifestyle modifications, including diet – with or without medications – underpin most management strategies.
“For the first time, we have provided a summary of all published studies on any dietary factor in association to all-cause mortality in individuals with type 2 diabetes,” said Dr. Barbaresko. “Moreover, the certainty of evidence has been evaluated for the first time.”
Matthias Schulze, MD, head of the German Institute of Human Nutrition, Berlin, moderated the session.
The new work “summarizes the available evidence, providing important dietary advice for patients with diabetes, for example, recommending whole grains,” he remarked. “However, the study also points to gaps in knowledge, so for many diet factors, we have either no or few studies, or study quality considered to be low, which calls for more research to fill the gap.”
High versus low intake of various dietary factors
The researchers performed meta-analyses based on published studies of all-cause mortality in individuals with type 2 diabetes aged 18 years and over, as associated with dietary patterns, macronutrients (carbohydrates, protein, fat), micronutrients (vitamins and minerals), secondary plant compounds (for example, polyphenols), and supplements.
Studies were conducted mainly in the United States and Europe with a mean follow-up of 10 years. Low and high intake were compared, and a dose-response relationship between different dietary factors and all-cause mortality was explored to generate summary risk ratios. The researchers also explored how the certainty of evidence was determined.
Decreased mortality from any cause was found for a higher intake of fish (SRR per serving/week, 0.95; over six studies); whole grain (SRR per 20 g/day, 0.84; two studies); fiber (SRR per 5 g/day, 0.86; three studies), and omega-3 polyunsaturated fatty acids (SRR per 0.1 g/day, 0.87; two studies).
A low certainty of evidence was found for an inverse association between all-cause mortality and vegetable consumption (SRR per 100 g/day, 0.88; two studies) and plant protein intake (SRR per 10 g/day, 0.91; three studies).
Eggs were associated with an increased risk of all-cause mortality (SRR per 10 g/day, 1.05; seven studies), as was dietary cholesterol (SRR per 300 mg/day, 1.19; two studies).
Regarding other dietary patterns, including the Mediterranean diet and low-carbohydrate diet, either no association was found and/or the evidence was very uncertain. Likewise, evidence was uncertain for foods including nuts, dairy, meat, sugar and sweets; macronutrients, including carbohydrates; and micronutrients, such as caffeine and vitamin D.
“With the Mediterranean diet, we saw an inverse association [with all-cause mortality] comparing high adherence with low adherence to the Mediterranean diet, but the certainty of evidence was very low, indicating a really uncertain meta-evidence,” remarked Dr. Barbaresko.
She concluded that a greater number of studies is needed to investigate the association of dietary factors with all-cause mortality in type 2 diabetes to strengthen the evidence for several other dietary factors. She also cautioned that meta-analyses are affected by unmeasured and residual confounding.
Dr. Barbaresko and Dr. Schulze reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT EASD 2022
Waist-hip ratio beats BMI for predicting obesity’s mortality risk
STOCKHOLM – New evidence continues to show that alternative measures of adiposity than body mass index, such as waist-to-hip ratio, work better for predicting the risk a person with overweight or obesity faces from their excess weight.
A direct comparison of waist-to-hip ratio (WHR), body mass index (BMI), and fat mass index (FMI) in a total of more than 380,000 United Kingdom residents included in the UK Biobank showed that WHR had the strongest and most consistent relationship to all-cause death, compared with the other two measures, indicating that clinicians should pay more attention to adiposity distribution than they do to BMI when prioritizing obesity interventions, Irfan Khan said at the annual meeting of the European Association for the Study of Diabetes.
Although it’s likely “way too early” to fully replace BMI as a measure of adiposity, because it is so established in guidelines and in practice, it is now time to “use WHR as an adjunct to BMI” suggested Mr. Khan in an interview.
“A lot of work still needs to be done to translate WHR into practice, but I think it’s getting closer,” said Mr. Khan, a medical student at McMaster University, Hamilton, Ont., who performed his analyses in collaboration with a research team based primarily at McMaster.
Moving away from BMI-centric obesity
“This is a timely topic, because guidelines for treating people with obesity have depended so much on BMI. We want to go from a BMI-centric view to a view of obesity that depends more on disease burden,” commented Matthias Blüher, MD, professor of molecular endocrinology and head of the Obesity Outpatient Clinic for Adults at the University of Leipzig (Germany).
For example, the 2016 obesity management guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology called for a “complications-centric” approach to assessing and intervening in people with obesity rather than a “BMI-centric” approach.
But Dr. Blüher went a step further in an interview, adding that “waist-to-hip ratio is now outdated,” with adjusted measures of WHR such as waist-to-height ratio “considered a better proxy for all-cause death.” He also gave high marks to the Edmonton Obesity Staging System, which independently added to BMI as well as to a diagnosis of metabolic syndrome for predicting mortality in a sample from the U.S. National Health and Nutrition Examination Survey (NHANES). The Edmonton System also surpassed BMI for disease-severity staging using data from more than 23,000 Canadians with a BMI that denoted obesity.
1 standard deviation increase in WHR linked with a 41% increased mortality
The study reported by Mr. Khan used both epidemiologic and Mendelian randomization analyses on data collected from more than 380,000 U.K. residents included in the UK Biobank database to examine the statistical associations between BMI, FMI, and WHR and all-cause death. This showed that while BMI and FMI both had significant, independent associations with all-cause mortality, with hazard ratios of 1.14 for each 1 standard deviation increase in BMI and of 1.17 for each standard deviation increase in FMI, the link was a stronger 1.41 per standard deviation increase in WHR, he said.
Another analysis that divided the entire UK Biobank study cohort into 20 roughly similar subgroups by their BMI showed that WHR had the most consistent association across the BMI spectrum.
Further analyses showed that WHR also strongly and significantly linked with cardiovascular disease death and with other causes of death that were not cardiovascular, cancer-related, or associated with respiratory diseases. And the WHR link to all-cause mortality was strongest in men, and much less robust in women, likely because visceral adiposity is much more common among men, even compared with the postmenopausal women who predominate in the UK Biobank cohort.
One more feature of WHR that makes it an attractive metric is its relative ease of measurement, about as easy as BMI, Mr. Khan said.
The study received no commercial funding, and Mr. Khan had no disclosures. Dr. Blüher has been a consultant to or speaker on behalf of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, and Sanofi.
STOCKHOLM – New evidence continues to show that alternative measures of adiposity than body mass index, such as waist-to-hip ratio, work better for predicting the risk a person with overweight or obesity faces from their excess weight.
A direct comparison of waist-to-hip ratio (WHR), body mass index (BMI), and fat mass index (FMI) in a total of more than 380,000 United Kingdom residents included in the UK Biobank showed that WHR had the strongest and most consistent relationship to all-cause death, compared with the other two measures, indicating that clinicians should pay more attention to adiposity distribution than they do to BMI when prioritizing obesity interventions, Irfan Khan said at the annual meeting of the European Association for the Study of Diabetes.
Although it’s likely “way too early” to fully replace BMI as a measure of adiposity, because it is so established in guidelines and in practice, it is now time to “use WHR as an adjunct to BMI” suggested Mr. Khan in an interview.
“A lot of work still needs to be done to translate WHR into practice, but I think it’s getting closer,” said Mr. Khan, a medical student at McMaster University, Hamilton, Ont., who performed his analyses in collaboration with a research team based primarily at McMaster.
Moving away from BMI-centric obesity
“This is a timely topic, because guidelines for treating people with obesity have depended so much on BMI. We want to go from a BMI-centric view to a view of obesity that depends more on disease burden,” commented Matthias Blüher, MD, professor of molecular endocrinology and head of the Obesity Outpatient Clinic for Adults at the University of Leipzig (Germany).
For example, the 2016 obesity management guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology called for a “complications-centric” approach to assessing and intervening in people with obesity rather than a “BMI-centric” approach.
But Dr. Blüher went a step further in an interview, adding that “waist-to-hip ratio is now outdated,” with adjusted measures of WHR such as waist-to-height ratio “considered a better proxy for all-cause death.” He also gave high marks to the Edmonton Obesity Staging System, which independently added to BMI as well as to a diagnosis of metabolic syndrome for predicting mortality in a sample from the U.S. National Health and Nutrition Examination Survey (NHANES). The Edmonton System also surpassed BMI for disease-severity staging using data from more than 23,000 Canadians with a BMI that denoted obesity.
1 standard deviation increase in WHR linked with a 41% increased mortality
The study reported by Mr. Khan used both epidemiologic and Mendelian randomization analyses on data collected from more than 380,000 U.K. residents included in the UK Biobank database to examine the statistical associations between BMI, FMI, and WHR and all-cause death. This showed that while BMI and FMI both had significant, independent associations with all-cause mortality, with hazard ratios of 1.14 for each 1 standard deviation increase in BMI and of 1.17 for each standard deviation increase in FMI, the link was a stronger 1.41 per standard deviation increase in WHR, he said.
Another analysis that divided the entire UK Biobank study cohort into 20 roughly similar subgroups by their BMI showed that WHR had the most consistent association across the BMI spectrum.
Further analyses showed that WHR also strongly and significantly linked with cardiovascular disease death and with other causes of death that were not cardiovascular, cancer-related, or associated with respiratory diseases. And the WHR link to all-cause mortality was strongest in men, and much less robust in women, likely because visceral adiposity is much more common among men, even compared with the postmenopausal women who predominate in the UK Biobank cohort.
One more feature of WHR that makes it an attractive metric is its relative ease of measurement, about as easy as BMI, Mr. Khan said.
The study received no commercial funding, and Mr. Khan had no disclosures. Dr. Blüher has been a consultant to or speaker on behalf of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, and Sanofi.
STOCKHOLM – New evidence continues to show that alternative measures of adiposity than body mass index, such as waist-to-hip ratio, work better for predicting the risk a person with overweight or obesity faces from their excess weight.
A direct comparison of waist-to-hip ratio (WHR), body mass index (BMI), and fat mass index (FMI) in a total of more than 380,000 United Kingdom residents included in the UK Biobank showed that WHR had the strongest and most consistent relationship to all-cause death, compared with the other two measures, indicating that clinicians should pay more attention to adiposity distribution than they do to BMI when prioritizing obesity interventions, Irfan Khan said at the annual meeting of the European Association for the Study of Diabetes.
Although it’s likely “way too early” to fully replace BMI as a measure of adiposity, because it is so established in guidelines and in practice, it is now time to “use WHR as an adjunct to BMI” suggested Mr. Khan in an interview.
“A lot of work still needs to be done to translate WHR into practice, but I think it’s getting closer,” said Mr. Khan, a medical student at McMaster University, Hamilton, Ont., who performed his analyses in collaboration with a research team based primarily at McMaster.
Moving away from BMI-centric obesity
“This is a timely topic, because guidelines for treating people with obesity have depended so much on BMI. We want to go from a BMI-centric view to a view of obesity that depends more on disease burden,” commented Matthias Blüher, MD, professor of molecular endocrinology and head of the Obesity Outpatient Clinic for Adults at the University of Leipzig (Germany).
For example, the 2016 obesity management guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology called for a “complications-centric” approach to assessing and intervening in people with obesity rather than a “BMI-centric” approach.
But Dr. Blüher went a step further in an interview, adding that “waist-to-hip ratio is now outdated,” with adjusted measures of WHR such as waist-to-height ratio “considered a better proxy for all-cause death.” He also gave high marks to the Edmonton Obesity Staging System, which independently added to BMI as well as to a diagnosis of metabolic syndrome for predicting mortality in a sample from the U.S. National Health and Nutrition Examination Survey (NHANES). The Edmonton System also surpassed BMI for disease-severity staging using data from more than 23,000 Canadians with a BMI that denoted obesity.
1 standard deviation increase in WHR linked with a 41% increased mortality
The study reported by Mr. Khan used both epidemiologic and Mendelian randomization analyses on data collected from more than 380,000 U.K. residents included in the UK Biobank database to examine the statistical associations between BMI, FMI, and WHR and all-cause death. This showed that while BMI and FMI both had significant, independent associations with all-cause mortality, with hazard ratios of 1.14 for each 1 standard deviation increase in BMI and of 1.17 for each standard deviation increase in FMI, the link was a stronger 1.41 per standard deviation increase in WHR, he said.
Another analysis that divided the entire UK Biobank study cohort into 20 roughly similar subgroups by their BMI showed that WHR had the most consistent association across the BMI spectrum.
Further analyses showed that WHR also strongly and significantly linked with cardiovascular disease death and with other causes of death that were not cardiovascular, cancer-related, or associated with respiratory diseases. And the WHR link to all-cause mortality was strongest in men, and much less robust in women, likely because visceral adiposity is much more common among men, even compared with the postmenopausal women who predominate in the UK Biobank cohort.
One more feature of WHR that makes it an attractive metric is its relative ease of measurement, about as easy as BMI, Mr. Khan said.
The study received no commercial funding, and Mr. Khan had no disclosures. Dr. Blüher has been a consultant to or speaker on behalf of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, and Sanofi.
AT EASD 2022
‘Game changer’ semaglutide halves diabetes risk from obesity
Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.
This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.
The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.
Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
GLP-1 agonists as complication-reducing agents
Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.
Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.
Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.
Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.
He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.
“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
Combined analysis of STEP 1 and STEP 4 data
The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.
A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.
Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.
“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.
In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.
The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.
Blood glucose changes confer the biggest effect
The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.
“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.
Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.
Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).
Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.
The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.
The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.
This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.
The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.
Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
GLP-1 agonists as complication-reducing agents
Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.
Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.
Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.
Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.
He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.
“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
Combined analysis of STEP 1 and STEP 4 data
The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.
A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.
Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.
“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.
In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.
The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.
Blood glucose changes confer the biggest effect
The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.
“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.
Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.
Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).
Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.
The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.
The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.
This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.
The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.
Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
GLP-1 agonists as complication-reducing agents
Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.
Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.
Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.
Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.
He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.
“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
Combined analysis of STEP 1 and STEP 4 data
The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.
A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.
Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.
“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.
In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.
The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.
Blood glucose changes confer the biggest effect
The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.
“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.
Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.
Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).
Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.
The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.
The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.
A version of this article first appeared on Medscape.com.
WHO releases six ‘action steps’ to combat global disparities in Parkinson’s disease
Since 2000, Parkinson’s disease has increased 81% and related deaths have increased 100% globally. In addition, many patients affected by Parkinson’s disease live in low- and middle-income countries and experience large inequalities in access to neurologic care and essential medicines.
To address these issues, the Brain Health Unit at the WHO developed six “action steps” it says are urgently required to combat global disparities in Parkinson’s disease.
The need for action is great, said lead author Nicoline Schiess, MD, MPH, a neurologist and technical officer in the WHO’s Brain Health Unit in Geneva.
“In adults, disorders of the nervous system are the leading cause of disability adjusted life years, or DALYs, and the second leading cause of death globally, accounting for 9 million deaths per year,” Dr. Schiess said.
The WHO’s recommendations were published online recently as a “Special Communication” in JAMA Neurology.
Serious public health challenge
Parkinson’s disease is the fastest growing disorder in terms of death and disability, and it is estimated that it caused 329,000 deaths in 2019 – an increase of more than 100% since 2000.
“The rise in cases is thought to be multifactorial and is likely affected by factors such as aging populations and environmental exposures, such as certain pesticides. With these rapidly increasing numbers, compounded by a lack of specialists and medicines in low- and middle-income countries, Parkinson’s disease presents a serious public health challenge,” Dr. Schiess said.
The publication of the six action steps is targeted toward clinicians and researchers who work in Parkinson’s disease, she added. The steps address the following areas:
- 1. Disease burden
- 2. Advocacy and awareness
- 3. Prevention and risk reduction
- 4. Diagnosis, treatment, and care
- 5. Caregiver support
- 6. Research
Dr. Schiess noted that data on disease burden are lacking in certain areas of the world, such as low- and middle-income countries, and information “based on race and ethnicity are inconsistent. Studies are needed to establish more representative epidemiological data.”
She said that advocacy and awareness are particularly important since young people may not be aware they can also develop Parkinson’s disease, and sex and race differences can factor in to the potential for delays in diagnosis and care. “This is often due to the incorrect perception that Parkinson’s disease only affects older people,” she noted.
In addition, “a substantial need exists to identify risks for Parkinson’s disease – in particular the risks we can mitigate,” said Dr. Schiess, citing pesticide exposure as one example. “The evidence linking pesticide exposure, for example paraquat and chlorpyrifos, with the risk of developing Parkinson’s disease is substantial. And yet in many countries, these products are still being used.”
Under the heading of diagnosis, treatment, and care, Dr. Schiess noted that patients with Parkinson’s disease in “low resource settings” and low- to middle-income countries are unable to obtain “even the most basic medications” to treat Parkinson’s disease.
“Strengthening health and social systems, and building capacity to improve medical care, including rehabilitation and palliative care and medication access, are vital. Also, education and training of primary health care professionals, growing the neurological workforce, and increasing the use of digital technology such as telemedicine, are key mechanisms to improving diagnosis and sustainability of care,” she said.
For caregiver support, Dr. Schiess pointed out that the progressive nature of the disease and timing of onset are contributors to increased caregiver burden. Other contributors, as the disease advances in a patient, include the development of cognitive impairment, psychiatric manifestations, and sleep disruption.
“Solutions that could decrease the burden on caregivers include providing an accurate and timely diagnosis and training and education to caregivers, such as the WHO iSUPPORT program, as well as psychosocial, financial, and community-based support,” said Dr. Schiess.
For research, she noted that the amount of studies in the field of Parkinson’s disease has grown because of increased funding and a greater number of initiatives over the past 2 decades.
“Continuing to build on this momentum is important in order to generate new treatment options, better care, and research capacity, especially in low- and middle-income countries,” she said.
Dr. Schiess emphasized the urgency for adopting these measures as cases of Parkinson’s disease continue to rise.
“The take-away message for clinicians is that Parkinson disease is a growing global public health issue. There is a pressing need for a global public health response to address health and social requirements for people with Parkinson’s disease,” she said.
Dr. Schiess reports having received grants from the Edmond J. Safra Foundation paid to her institution during the conduct of the study.
A version of this article first appeared on Medscape.com.
Since 2000, Parkinson’s disease has increased 81% and related deaths have increased 100% globally. In addition, many patients affected by Parkinson’s disease live in low- and middle-income countries and experience large inequalities in access to neurologic care and essential medicines.
To address these issues, the Brain Health Unit at the WHO developed six “action steps” it says are urgently required to combat global disparities in Parkinson’s disease.
The need for action is great, said lead author Nicoline Schiess, MD, MPH, a neurologist and technical officer in the WHO’s Brain Health Unit in Geneva.
“In adults, disorders of the nervous system are the leading cause of disability adjusted life years, or DALYs, and the second leading cause of death globally, accounting for 9 million deaths per year,” Dr. Schiess said.
The WHO’s recommendations were published online recently as a “Special Communication” in JAMA Neurology.
Serious public health challenge
Parkinson’s disease is the fastest growing disorder in terms of death and disability, and it is estimated that it caused 329,000 deaths in 2019 – an increase of more than 100% since 2000.
“The rise in cases is thought to be multifactorial and is likely affected by factors such as aging populations and environmental exposures, such as certain pesticides. With these rapidly increasing numbers, compounded by a lack of specialists and medicines in low- and middle-income countries, Parkinson’s disease presents a serious public health challenge,” Dr. Schiess said.
The publication of the six action steps is targeted toward clinicians and researchers who work in Parkinson’s disease, she added. The steps address the following areas:
- 1. Disease burden
- 2. Advocacy and awareness
- 3. Prevention and risk reduction
- 4. Diagnosis, treatment, and care
- 5. Caregiver support
- 6. Research
Dr. Schiess noted that data on disease burden are lacking in certain areas of the world, such as low- and middle-income countries, and information “based on race and ethnicity are inconsistent. Studies are needed to establish more representative epidemiological data.”
She said that advocacy and awareness are particularly important since young people may not be aware they can also develop Parkinson’s disease, and sex and race differences can factor in to the potential for delays in diagnosis and care. “This is often due to the incorrect perception that Parkinson’s disease only affects older people,” she noted.
In addition, “a substantial need exists to identify risks for Parkinson’s disease – in particular the risks we can mitigate,” said Dr. Schiess, citing pesticide exposure as one example. “The evidence linking pesticide exposure, for example paraquat and chlorpyrifos, with the risk of developing Parkinson’s disease is substantial. And yet in many countries, these products are still being used.”
Under the heading of diagnosis, treatment, and care, Dr. Schiess noted that patients with Parkinson’s disease in “low resource settings” and low- to middle-income countries are unable to obtain “even the most basic medications” to treat Parkinson’s disease.
“Strengthening health and social systems, and building capacity to improve medical care, including rehabilitation and palliative care and medication access, are vital. Also, education and training of primary health care professionals, growing the neurological workforce, and increasing the use of digital technology such as telemedicine, are key mechanisms to improving diagnosis and sustainability of care,” she said.
For caregiver support, Dr. Schiess pointed out that the progressive nature of the disease and timing of onset are contributors to increased caregiver burden. Other contributors, as the disease advances in a patient, include the development of cognitive impairment, psychiatric manifestations, and sleep disruption.
“Solutions that could decrease the burden on caregivers include providing an accurate and timely diagnosis and training and education to caregivers, such as the WHO iSUPPORT program, as well as psychosocial, financial, and community-based support,” said Dr. Schiess.
For research, she noted that the amount of studies in the field of Parkinson’s disease has grown because of increased funding and a greater number of initiatives over the past 2 decades.
“Continuing to build on this momentum is important in order to generate new treatment options, better care, and research capacity, especially in low- and middle-income countries,” she said.
Dr. Schiess emphasized the urgency for adopting these measures as cases of Parkinson’s disease continue to rise.
“The take-away message for clinicians is that Parkinson disease is a growing global public health issue. There is a pressing need for a global public health response to address health and social requirements for people with Parkinson’s disease,” she said.
Dr. Schiess reports having received grants from the Edmond J. Safra Foundation paid to her institution during the conduct of the study.
A version of this article first appeared on Medscape.com.
Since 2000, Parkinson’s disease has increased 81% and related deaths have increased 100% globally. In addition, many patients affected by Parkinson’s disease live in low- and middle-income countries and experience large inequalities in access to neurologic care and essential medicines.
To address these issues, the Brain Health Unit at the WHO developed six “action steps” it says are urgently required to combat global disparities in Parkinson’s disease.
The need for action is great, said lead author Nicoline Schiess, MD, MPH, a neurologist and technical officer in the WHO’s Brain Health Unit in Geneva.
“In adults, disorders of the nervous system are the leading cause of disability adjusted life years, or DALYs, and the second leading cause of death globally, accounting for 9 million deaths per year,” Dr. Schiess said.
The WHO’s recommendations were published online recently as a “Special Communication” in JAMA Neurology.
Serious public health challenge
Parkinson’s disease is the fastest growing disorder in terms of death and disability, and it is estimated that it caused 329,000 deaths in 2019 – an increase of more than 100% since 2000.
“The rise in cases is thought to be multifactorial and is likely affected by factors such as aging populations and environmental exposures, such as certain pesticides. With these rapidly increasing numbers, compounded by a lack of specialists and medicines in low- and middle-income countries, Parkinson’s disease presents a serious public health challenge,” Dr. Schiess said.
The publication of the six action steps is targeted toward clinicians and researchers who work in Parkinson’s disease, she added. The steps address the following areas:
- 1. Disease burden
- 2. Advocacy and awareness
- 3. Prevention and risk reduction
- 4. Diagnosis, treatment, and care
- 5. Caregiver support
- 6. Research
Dr. Schiess noted that data on disease burden are lacking in certain areas of the world, such as low- and middle-income countries, and information “based on race and ethnicity are inconsistent. Studies are needed to establish more representative epidemiological data.”
She said that advocacy and awareness are particularly important since young people may not be aware they can also develop Parkinson’s disease, and sex and race differences can factor in to the potential for delays in diagnosis and care. “This is often due to the incorrect perception that Parkinson’s disease only affects older people,” she noted.
In addition, “a substantial need exists to identify risks for Parkinson’s disease – in particular the risks we can mitigate,” said Dr. Schiess, citing pesticide exposure as one example. “The evidence linking pesticide exposure, for example paraquat and chlorpyrifos, with the risk of developing Parkinson’s disease is substantial. And yet in many countries, these products are still being used.”
Under the heading of diagnosis, treatment, and care, Dr. Schiess noted that patients with Parkinson’s disease in “low resource settings” and low- to middle-income countries are unable to obtain “even the most basic medications” to treat Parkinson’s disease.
“Strengthening health and social systems, and building capacity to improve medical care, including rehabilitation and palliative care and medication access, are vital. Also, education and training of primary health care professionals, growing the neurological workforce, and increasing the use of digital technology such as telemedicine, are key mechanisms to improving diagnosis and sustainability of care,” she said.
For caregiver support, Dr. Schiess pointed out that the progressive nature of the disease and timing of onset are contributors to increased caregiver burden. Other contributors, as the disease advances in a patient, include the development of cognitive impairment, psychiatric manifestations, and sleep disruption.
“Solutions that could decrease the burden on caregivers include providing an accurate and timely diagnosis and training and education to caregivers, such as the WHO iSUPPORT program, as well as psychosocial, financial, and community-based support,” said Dr. Schiess.
For research, she noted that the amount of studies in the field of Parkinson’s disease has grown because of increased funding and a greater number of initiatives over the past 2 decades.
“Continuing to build on this momentum is important in order to generate new treatment options, better care, and research capacity, especially in low- and middle-income countries,” she said.
Dr. Schiess emphasized the urgency for adopting these measures as cases of Parkinson’s disease continue to rise.
“The take-away message for clinicians is that Parkinson disease is a growing global public health issue. There is a pressing need for a global public health response to address health and social requirements for people with Parkinson’s disease,” she said.
Dr. Schiess reports having received grants from the Edmond J. Safra Foundation paid to her institution during the conduct of the study.
A version of this article first appeared on Medscape.com.