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Meet the rare diabetes diagnosis that thrills patients
ORLANDO – Liana K. Billings, MD, an endocrinologist at the University of Chicago and the NorthShore University HealthSystem in Skokie, Ill., loves the thrill of letting patients know they have a rare kind of diabetes. “Once you do this once, you don’t want to stop,” she told colleagues in a presentation at the annual scientific sessions of the American Diabetes Association.
Yes, it’s true: There’s a diabetes diagnosis that spawns good feelings like delight and relief. The cause for celebration is a condition known as monogenetic diabetes, also known as maturity-onset diabetes of the young (MODY) if it develops after the neonatal period.
“The reason that getting a diagnosis of MODY can be a ‘good’ diagnosis is because the three most common forms of MODY have gene-specific treatments that typically improve patients’ glycemic control and are less onerous than the treatments patients were previously receiving when they were thought to have type 1 or type 2 diabetes,” explained Miriam S. Udler, MD, PhD, of Massachusetts General Hospital and Harvard Medical School, Boston, in an interview.
Dr. Udler and Dr. Billings spoke to colleagues about monogenetic diabetes in their presentation at the ADA meeting.
Research has suggested that 1%-4% of people with diabetes have the monogenetic form, in which the condition is caused by changes in a single gene. A 2017 British study of 1,407 patients with diabetes reported that “the minimum prevalence of monogenic diabetes is 3.6% of patients diagnosed at age 30 years or younger.”
The study, which tested a screening regimen, also turned up 17 new diagnoses of monogenetic diabetes among the 1,407 patients, doubling the total. The findings reflect an apparent fact about monogenetic diabetes: Physicians often don’t look for it, even though a diagnosis can be a godsend – especially for those who were previously diagnosed with type 1 or type 2 and placed on treatment regimens that are unnecessary at best and harmful at worst. (Diabetes Care. 2017 Aug;40[8]: 1017-25)
Patients with the MODY variant in the GCK gene, for example, “can generally stop all medications because they are not at risk for clinically significant complications of diabetes,” Dr. Udler said. “Patients with HNF1A and HNF4A variants can often be switched from insulin injections to ... a sulfonylurea, which is easier to take than insulin injections, and patients generally have better glycemic control after switching to pills.”
Unfortunately for doctors and patients, it can be complicated and costly to test for monogenetic diabetes. But screening tools are available to help physicians make choices about whether to launch testing in the first place, according to Dr. Udler and Dr. Billings.
There are two forms of monogenetic diabetes – neonatal diabetes, which is diagnosed by age 6-9 months, and MODY, which is typically diagnosed in those aged between 10 and 25 years, noted Dr. Billings.
Reasons to suspect MODY include early onset of diabetes (under 35 years), a family history of diabetes, a lack of obesity, and negative islet-cell antibodies, she said.
Obese patients may also have the condition: A 2017 American study of 488 overweight and obese children and adolescents diagnosed with type 2 diabetes found that 4.5% actually had monogenetic diabetes. (Genet Med. 2018 Jun;20[6]:583-90).
Once a physician suspects MODY, physicians may consult the University of Exeter’s risk calculator. It provides guidance about whether a test is a good idea. Dr. Billings cautioned, however, that the value of a calculator’s estimate of risk is not all-encompassing. “You should never use the calculator by itself as a reason to not pursue your intuition,” she said.
Dr. Udler noted that the University of Exeter calculator has important limitations, such as its reliance on specific genes, its lack of consideration of family history outside of parents, and its reliance on the experiences of white European patients.
As for tests, the University of Chicago and the University of Exeter both offer free genetic testing for neonatal diabetes, Dr. Billings said in her presentation.
Monogenetic diabetes tests in older children and adults are not free. However, Dr. Udler said the tests are often covered by insurance companies whether done for one or more genes.
At least one company offers a direct-to-consumer monogenetic diabetes test, according to Dr. Udler, but she recommended against it, especially in light of a curious online notice that says the test isn’t intended to be diagnostic. “I’m not sure what this would be useful for then,” she said.
For her part, Dr. Billings cautioned that test results may be inconclusive, and tests may offer different answers. She also recommended referring patients to genetic counseling.
Dr. Udler reported a board member/advisory panel relationship with Encompass Bioscience. Dr. Billings reported relationships with Novo Nordisk, Sanofi, and Dexcom.
ORLANDO – Liana K. Billings, MD, an endocrinologist at the University of Chicago and the NorthShore University HealthSystem in Skokie, Ill., loves the thrill of letting patients know they have a rare kind of diabetes. “Once you do this once, you don’t want to stop,” she told colleagues in a presentation at the annual scientific sessions of the American Diabetes Association.
Yes, it’s true: There’s a diabetes diagnosis that spawns good feelings like delight and relief. The cause for celebration is a condition known as monogenetic diabetes, also known as maturity-onset diabetes of the young (MODY) if it develops after the neonatal period.
“The reason that getting a diagnosis of MODY can be a ‘good’ diagnosis is because the three most common forms of MODY have gene-specific treatments that typically improve patients’ glycemic control and are less onerous than the treatments patients were previously receiving when they were thought to have type 1 or type 2 diabetes,” explained Miriam S. Udler, MD, PhD, of Massachusetts General Hospital and Harvard Medical School, Boston, in an interview.
Dr. Udler and Dr. Billings spoke to colleagues about monogenetic diabetes in their presentation at the ADA meeting.
Research has suggested that 1%-4% of people with diabetes have the monogenetic form, in which the condition is caused by changes in a single gene. A 2017 British study of 1,407 patients with diabetes reported that “the minimum prevalence of monogenic diabetes is 3.6% of patients diagnosed at age 30 years or younger.”
The study, which tested a screening regimen, also turned up 17 new diagnoses of monogenetic diabetes among the 1,407 patients, doubling the total. The findings reflect an apparent fact about monogenetic diabetes: Physicians often don’t look for it, even though a diagnosis can be a godsend – especially for those who were previously diagnosed with type 1 or type 2 and placed on treatment regimens that are unnecessary at best and harmful at worst. (Diabetes Care. 2017 Aug;40[8]: 1017-25)
Patients with the MODY variant in the GCK gene, for example, “can generally stop all medications because they are not at risk for clinically significant complications of diabetes,” Dr. Udler said. “Patients with HNF1A and HNF4A variants can often be switched from insulin injections to ... a sulfonylurea, which is easier to take than insulin injections, and patients generally have better glycemic control after switching to pills.”
Unfortunately for doctors and patients, it can be complicated and costly to test for monogenetic diabetes. But screening tools are available to help physicians make choices about whether to launch testing in the first place, according to Dr. Udler and Dr. Billings.
There are two forms of monogenetic diabetes – neonatal diabetes, which is diagnosed by age 6-9 months, and MODY, which is typically diagnosed in those aged between 10 and 25 years, noted Dr. Billings.
Reasons to suspect MODY include early onset of diabetes (under 35 years), a family history of diabetes, a lack of obesity, and negative islet-cell antibodies, she said.
Obese patients may also have the condition: A 2017 American study of 488 overweight and obese children and adolescents diagnosed with type 2 diabetes found that 4.5% actually had monogenetic diabetes. (Genet Med. 2018 Jun;20[6]:583-90).
Once a physician suspects MODY, physicians may consult the University of Exeter’s risk calculator. It provides guidance about whether a test is a good idea. Dr. Billings cautioned, however, that the value of a calculator’s estimate of risk is not all-encompassing. “You should never use the calculator by itself as a reason to not pursue your intuition,” she said.
Dr. Udler noted that the University of Exeter calculator has important limitations, such as its reliance on specific genes, its lack of consideration of family history outside of parents, and its reliance on the experiences of white European patients.
As for tests, the University of Chicago and the University of Exeter both offer free genetic testing for neonatal diabetes, Dr. Billings said in her presentation.
Monogenetic diabetes tests in older children and adults are not free. However, Dr. Udler said the tests are often covered by insurance companies whether done for one or more genes.
At least one company offers a direct-to-consumer monogenetic diabetes test, according to Dr. Udler, but she recommended against it, especially in light of a curious online notice that says the test isn’t intended to be diagnostic. “I’m not sure what this would be useful for then,” she said.
For her part, Dr. Billings cautioned that test results may be inconclusive, and tests may offer different answers. She also recommended referring patients to genetic counseling.
Dr. Udler reported a board member/advisory panel relationship with Encompass Bioscience. Dr. Billings reported relationships with Novo Nordisk, Sanofi, and Dexcom.
ORLANDO – Liana K. Billings, MD, an endocrinologist at the University of Chicago and the NorthShore University HealthSystem in Skokie, Ill., loves the thrill of letting patients know they have a rare kind of diabetes. “Once you do this once, you don’t want to stop,” she told colleagues in a presentation at the annual scientific sessions of the American Diabetes Association.
Yes, it’s true: There’s a diabetes diagnosis that spawns good feelings like delight and relief. The cause for celebration is a condition known as monogenetic diabetes, also known as maturity-onset diabetes of the young (MODY) if it develops after the neonatal period.
“The reason that getting a diagnosis of MODY can be a ‘good’ diagnosis is because the three most common forms of MODY have gene-specific treatments that typically improve patients’ glycemic control and are less onerous than the treatments patients were previously receiving when they were thought to have type 1 or type 2 diabetes,” explained Miriam S. Udler, MD, PhD, of Massachusetts General Hospital and Harvard Medical School, Boston, in an interview.
Dr. Udler and Dr. Billings spoke to colleagues about monogenetic diabetes in their presentation at the ADA meeting.
Research has suggested that 1%-4% of people with diabetes have the monogenetic form, in which the condition is caused by changes in a single gene. A 2017 British study of 1,407 patients with diabetes reported that “the minimum prevalence of monogenic diabetes is 3.6% of patients diagnosed at age 30 years or younger.”
The study, which tested a screening regimen, also turned up 17 new diagnoses of monogenetic diabetes among the 1,407 patients, doubling the total. The findings reflect an apparent fact about monogenetic diabetes: Physicians often don’t look for it, even though a diagnosis can be a godsend – especially for those who were previously diagnosed with type 1 or type 2 and placed on treatment regimens that are unnecessary at best and harmful at worst. (Diabetes Care. 2017 Aug;40[8]: 1017-25)
Patients with the MODY variant in the GCK gene, for example, “can generally stop all medications because they are not at risk for clinically significant complications of diabetes,” Dr. Udler said. “Patients with HNF1A and HNF4A variants can often be switched from insulin injections to ... a sulfonylurea, which is easier to take than insulin injections, and patients generally have better glycemic control after switching to pills.”
Unfortunately for doctors and patients, it can be complicated and costly to test for monogenetic diabetes. But screening tools are available to help physicians make choices about whether to launch testing in the first place, according to Dr. Udler and Dr. Billings.
There are two forms of monogenetic diabetes – neonatal diabetes, which is diagnosed by age 6-9 months, and MODY, which is typically diagnosed in those aged between 10 and 25 years, noted Dr. Billings.
Reasons to suspect MODY include early onset of diabetes (under 35 years), a family history of diabetes, a lack of obesity, and negative islet-cell antibodies, she said.
Obese patients may also have the condition: A 2017 American study of 488 overweight and obese children and adolescents diagnosed with type 2 diabetes found that 4.5% actually had monogenetic diabetes. (Genet Med. 2018 Jun;20[6]:583-90).
Once a physician suspects MODY, physicians may consult the University of Exeter’s risk calculator. It provides guidance about whether a test is a good idea. Dr. Billings cautioned, however, that the value of a calculator’s estimate of risk is not all-encompassing. “You should never use the calculator by itself as a reason to not pursue your intuition,” she said.
Dr. Udler noted that the University of Exeter calculator has important limitations, such as its reliance on specific genes, its lack of consideration of family history outside of parents, and its reliance on the experiences of white European patients.
As for tests, the University of Chicago and the University of Exeter both offer free genetic testing for neonatal diabetes, Dr. Billings said in her presentation.
Monogenetic diabetes tests in older children and adults are not free. However, Dr. Udler said the tests are often covered by insurance companies whether done for one or more genes.
At least one company offers a direct-to-consumer monogenetic diabetes test, according to Dr. Udler, but she recommended against it, especially in light of a curious online notice that says the test isn’t intended to be diagnostic. “I’m not sure what this would be useful for then,” she said.
For her part, Dr. Billings cautioned that test results may be inconclusive, and tests may offer different answers. She also recommended referring patients to genetic counseling.
Dr. Udler reported a board member/advisory panel relationship with Encompass Bioscience. Dr. Billings reported relationships with Novo Nordisk, Sanofi, and Dexcom.
EXPERT ANALYSIS FROM ADA 2018
Looking at study results with a critical eye
As a physician you are the embodiment of delayed gratification. You spent more than 20 years in school before you earned a degree that then allowed you spend another 3-plus years in training before anyone would consider you a “real” doctor. Somewhere along that long and shallow trajectory someone may have said, “You must have done really well on the marshmallow test.”
That is, until this year, when an attempt to replicate the initial study by Shoda et al. failed to find that the associations between delayed gratification and adolescent achievement were anywhere near as significant as those reported in the 1990 study (Psychol Sci. 2018 May. doi: 10.1177/0956797618761661). Watts et al. suggest that the discrepancy may be explained in part by a failure to adequately control for family background, home environment, and early cognitive ability in the initial experimental design.
Is there a message here? Should we stop wasting our time reading papers from the developmental psychology literature? Not just yet. There are more papers coming out in which the authors attempt to replicate other landmark studies, often without success (“Undergrads Can Improve Psychology,” by Russel T. Warne and Jordan Wagge, The Wall Street Journal, June 20, 2018). Let’s wait and see how much more debunking there is going to be before we throw the baby out with the bath water.
regardless of how prestigious the institution of origin and regardless of how much it appeals to our common sense. Our intuition can be a powerful tool when we are looking for answers, but it can lead us astray if we take it too seriously.
It is often said that a good experiment is one that raises more questions than it answers. You don’t have to remember all that stuff you learned when you studied statistics to be able to question the results of a study you read in a peer-reviewed journal. I find that in many of the papers I read I have serious concerns about how well the authors have controlled for the not-so-obvious variables.
So where does this failed attempt at replicating the original marshmallow test study leave us? It is still very likely given your aptitude for delayed gratification that had you been given the test as a preschooler you would not have even touched the marshmallow until the experimenter re-entered the room to end the test and then ... you probably would have offered to share it with her.
But these new results suggest that your ability to delay gratification was not some skill with which you were born. You may have been born smarter than the average child, but your skill at delaying gratification may have been one you learned from your parents and assimilated from the home environment in which your grew up. This may be one of those nature-or-nurture skirmishes in which nurture wins. And, it may be another good example of the importance of the first 3 or 4 years in a child’s emotional and psychological development.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
As a physician you are the embodiment of delayed gratification. You spent more than 20 years in school before you earned a degree that then allowed you spend another 3-plus years in training before anyone would consider you a “real” doctor. Somewhere along that long and shallow trajectory someone may have said, “You must have done really well on the marshmallow test.”
That is, until this year, when an attempt to replicate the initial study by Shoda et al. failed to find that the associations between delayed gratification and adolescent achievement were anywhere near as significant as those reported in the 1990 study (Psychol Sci. 2018 May. doi: 10.1177/0956797618761661). Watts et al. suggest that the discrepancy may be explained in part by a failure to adequately control for family background, home environment, and early cognitive ability in the initial experimental design.
Is there a message here? Should we stop wasting our time reading papers from the developmental psychology literature? Not just yet. There are more papers coming out in which the authors attempt to replicate other landmark studies, often without success (“Undergrads Can Improve Psychology,” by Russel T. Warne and Jordan Wagge, The Wall Street Journal, June 20, 2018). Let’s wait and see how much more debunking there is going to be before we throw the baby out with the bath water.
regardless of how prestigious the institution of origin and regardless of how much it appeals to our common sense. Our intuition can be a powerful tool when we are looking for answers, but it can lead us astray if we take it too seriously.
It is often said that a good experiment is one that raises more questions than it answers. You don’t have to remember all that stuff you learned when you studied statistics to be able to question the results of a study you read in a peer-reviewed journal. I find that in many of the papers I read I have serious concerns about how well the authors have controlled for the not-so-obvious variables.
So where does this failed attempt at replicating the original marshmallow test study leave us? It is still very likely given your aptitude for delayed gratification that had you been given the test as a preschooler you would not have even touched the marshmallow until the experimenter re-entered the room to end the test and then ... you probably would have offered to share it with her.
But these new results suggest that your ability to delay gratification was not some skill with which you were born. You may have been born smarter than the average child, but your skill at delaying gratification may have been one you learned from your parents and assimilated from the home environment in which your grew up. This may be one of those nature-or-nurture skirmishes in which nurture wins. And, it may be another good example of the importance of the first 3 or 4 years in a child’s emotional and psychological development.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
As a physician you are the embodiment of delayed gratification. You spent more than 20 years in school before you earned a degree that then allowed you spend another 3-plus years in training before anyone would consider you a “real” doctor. Somewhere along that long and shallow trajectory someone may have said, “You must have done really well on the marshmallow test.”
That is, until this year, when an attempt to replicate the initial study by Shoda et al. failed to find that the associations between delayed gratification and adolescent achievement were anywhere near as significant as those reported in the 1990 study (Psychol Sci. 2018 May. doi: 10.1177/0956797618761661). Watts et al. suggest that the discrepancy may be explained in part by a failure to adequately control for family background, home environment, and early cognitive ability in the initial experimental design.
Is there a message here? Should we stop wasting our time reading papers from the developmental psychology literature? Not just yet. There are more papers coming out in which the authors attempt to replicate other landmark studies, often without success (“Undergrads Can Improve Psychology,” by Russel T. Warne and Jordan Wagge, The Wall Street Journal, June 20, 2018). Let’s wait and see how much more debunking there is going to be before we throw the baby out with the bath water.
regardless of how prestigious the institution of origin and regardless of how much it appeals to our common sense. Our intuition can be a powerful tool when we are looking for answers, but it can lead us astray if we take it too seriously.
It is often said that a good experiment is one that raises more questions than it answers. You don’t have to remember all that stuff you learned when you studied statistics to be able to question the results of a study you read in a peer-reviewed journal. I find that in many of the papers I read I have serious concerns about how well the authors have controlled for the not-so-obvious variables.
So where does this failed attempt at replicating the original marshmallow test study leave us? It is still very likely given your aptitude for delayed gratification that had you been given the test as a preschooler you would not have even touched the marshmallow until the experimenter re-entered the room to end the test and then ... you probably would have offered to share it with her.
But these new results suggest that your ability to delay gratification was not some skill with which you were born. You may have been born smarter than the average child, but your skill at delaying gratification may have been one you learned from your parents and assimilated from the home environment in which your grew up. This may be one of those nature-or-nurture skirmishes in which nurture wins. And, it may be another good example of the importance of the first 3 or 4 years in a child’s emotional and psychological development.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
Should you be worried about the declining birth rate?
The number of births in the United States has fallen for the second year in a row. Births in 2017 were down 2% from 2016, bringing the birth rate to a 30-year low at 60 births per 1,000 women aged 15-44 years. This decline spanned nearly all maternal age groups, including teenagers (Hamilton et al. NVSS Vital Statistics Rapid Release Report No 004, May 2018).
In the crudest terms, babies represent the raw material of pediatrics. Without children, we pediatricians would have to begin treating those whining adults. Most of us chose pediatrics because we enjoy being around children, and many of us were motivated to study medicine by a desire to help sick children. Is this decline in the supply stream of patients something we should be worrying about?
Before we start looking for other less appealing employment opportunities, let’s look a little closer at the reasons for this declining birth rate. A traditional explanation cites an association between the number of births and the health of the economy. However, this recent decline has occurred in the face of an obviously improving economy.
In an attempt to find a more nuanced explanation, the New York Times asked a nationally representative sample of 1,858 young adults aged 20-45 years how they felt about having children (“Americans Are Having Fewer Babies. They Told Us Why.” by Claire Cain Miller, July 5, 2018). The results were interesting and not necessarily surprising. When the respondents were asked why they had or were expecting to have fewer children than they considered ideal, six of their first eight reasons were linked to their finances, with “Child care is too expensive” leading all answers at 64%. The second highest response was “Want more time for the children I have” (54%) and the sixth was “Want more leisure time”(42%).
When the young adults were asked why they aren’t having children, “Want more leisure time” moved to No. 1 (32%) and “Can’t afford day care” fell to third place (31%) just ahead of “No desire for children” (30%).
Embedded in this data from the National Vital Statistic System (NVSS) and the New York Times poll are the seeds of reassurance. The observation that the young adults’ second reason for not wanting to have more children was that they wanted to have more time with the children they have suggests what pediatricians already have observed for a generation or two. Modern adults appear to be taking their role as parents more seriously. They worry that they aren’t doing a good job and look to us as one of their, if not their most, trusted advisers. 
This epidemic of parental anxiety does not appear to be abating with the declining birth rate. It continues to generate a large percentage of phone calls and office visits. Over the course of my career, it became clear that although there were fewer children being born in our community, pediatricians remained busy, but with a broader spectrum of complaints that tilted toward behavioral issues.
In the current NVSS data, the cesarean section rate rose again and is now 32%, and the preterm birth rate increased for the third year in a row to 10%. The birth rate for low-birth-weight infants climbed to 8%, the highest since 2006. So while the number of births has fallen to a 30-year low, there appear to be more high-risk babies being born.
You can worry about job security if you like, but in a quirky kind of way pediatrics is following along its own rules of supply and demand. And, you should rest easy ... that is until the next panicked call from a parent wakes you in the middle of the night.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
The number of births in the United States has fallen for the second year in a row. Births in 2017 were down 2% from 2016, bringing the birth rate to a 30-year low at 60 births per 1,000 women aged 15-44 years. This decline spanned nearly all maternal age groups, including teenagers (Hamilton et al. NVSS Vital Statistics Rapid Release Report No 004, May 2018).
In the crudest terms, babies represent the raw material of pediatrics. Without children, we pediatricians would have to begin treating those whining adults. Most of us chose pediatrics because we enjoy being around children, and many of us were motivated to study medicine by a desire to help sick children. Is this decline in the supply stream of patients something we should be worrying about?
Before we start looking for other less appealing employment opportunities, let’s look a little closer at the reasons for this declining birth rate. A traditional explanation cites an association between the number of births and the health of the economy. However, this recent decline has occurred in the face of an obviously improving economy.
In an attempt to find a more nuanced explanation, the New York Times asked a nationally representative sample of 1,858 young adults aged 20-45 years how they felt about having children (“Americans Are Having Fewer Babies. They Told Us Why.” by Claire Cain Miller, July 5, 2018). The results were interesting and not necessarily surprising. When the respondents were asked why they had or were expecting to have fewer children than they considered ideal, six of their first eight reasons were linked to their finances, with “Child care is too expensive” leading all answers at 64%. The second highest response was “Want more time for the children I have” (54%) and the sixth was “Want more leisure time”(42%).
When the young adults were asked why they aren’t having children, “Want more leisure time” moved to No. 1 (32%) and “Can’t afford day care” fell to third place (31%) just ahead of “No desire for children” (30%).
Embedded in this data from the National Vital Statistic System (NVSS) and the New York Times poll are the seeds of reassurance. The observation that the young adults’ second reason for not wanting to have more children was that they wanted to have more time with the children they have suggests what pediatricians already have observed for a generation or two. Modern adults appear to be taking their role as parents more seriously. They worry that they aren’t doing a good job and look to us as one of their, if not their most, trusted advisers.
This epidemic of parental anxiety does not appear to be abating with the declining birth rate. It continues to generate a large percentage of phone calls and office visits. Over the course of my career, it became clear that although there were fewer children being born in our community, pediatricians remained busy, but with a broader spectrum of complaints that tilted toward behavioral issues.
In the current NVSS data, the cesarean section rate rose again and is now 32%, and the preterm birth rate increased for the third year in a row to 10%. The birth rate for low-birth-weight infants climbed to 8%, the highest since 2006. So while the number of births has fallen to a 30-year low, there appear to be more high-risk babies being born.
You can worry about job security if you like, but in a quirky kind of way pediatrics is following along its own rules of supply and demand. And, you should rest easy ... that is until the next panicked call from a parent wakes you in the middle of the night.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
The number of births in the United States has fallen for the second year in a row. Births in 2017 were down 2% from 2016, bringing the birth rate to a 30-year low at 60 births per 1,000 women aged 15-44 years. This decline spanned nearly all maternal age groups, including teenagers (Hamilton et al. NVSS Vital Statistics Rapid Release Report No 004, May 2018).
In the crudest terms, babies represent the raw material of pediatrics. Without children, we pediatricians would have to begin treating those whining adults. Most of us chose pediatrics because we enjoy being around children, and many of us were motivated to study medicine by a desire to help sick children. Is this decline in the supply stream of patients something we should be worrying about?
Before we start looking for other less appealing employment opportunities, let’s look a little closer at the reasons for this declining birth rate. A traditional explanation cites an association between the number of births and the health of the economy. However, this recent decline has occurred in the face of an obviously improving economy.
In an attempt to find a more nuanced explanation, the New York Times asked a nationally representative sample of 1,858 young adults aged 20-45 years how they felt about having children (“Americans Are Having Fewer Babies. They Told Us Why.” by Claire Cain Miller, July 5, 2018). The results were interesting and not necessarily surprising. When the respondents were asked why they had or were expecting to have fewer children than they considered ideal, six of their first eight reasons were linked to their finances, with “Child care is too expensive” leading all answers at 64%. The second highest response was “Want more time for the children I have” (54%) and the sixth was “Want more leisure time”(42%).
When the young adults were asked why they aren’t having children, “Want more leisure time” moved to No. 1 (32%) and “Can’t afford day care” fell to third place (31%) just ahead of “No desire for children” (30%).
Embedded in this data from the National Vital Statistic System (NVSS) and the New York Times poll are the seeds of reassurance. The observation that the young adults’ second reason for not wanting to have more children was that they wanted to have more time with the children they have suggests what pediatricians already have observed for a generation or two. Modern adults appear to be taking their role as parents more seriously. They worry that they aren’t doing a good job and look to us as one of their, if not their most, trusted advisers.
This epidemic of parental anxiety does not appear to be abating with the declining birth rate. It continues to generate a large percentage of phone calls and office visits. Over the course of my career, it became clear that although there were fewer children being born in our community, pediatricians remained busy, but with a broader spectrum of complaints that tilted toward behavioral issues.
In the current NVSS data, the cesarean section rate rose again and is now 32%, and the preterm birth rate increased for the third year in a row to 10%. The birth rate for low-birth-weight infants climbed to 8%, the highest since 2006. So while the number of births has fallen to a 30-year low, there appear to be more high-risk babies being born.
You can worry about job security if you like, but in a quirky kind of way pediatrics is following along its own rules of supply and demand. And, you should rest easy ... that is until the next panicked call from a parent wakes you in the middle of the night.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
Early BCC seen in teen kidney transplant patient
A 17-year-old girl seen in a Portuguese dermatology clinic was found to have a nodular basal cell carcinoma on the parietal region of her scalp. The nodule appeared 6 years after she had received a kidney transplant, according to João Borges-Costa, MD, PhD, who submitted the case report.
Since the transplant, the girl had been maintained on immunosuppressive medication of tacrolimus 1 mg twice daily, mycophenolate sodium 360 mg twice daily, and prednisolone 10 mg every other day. The 1-cm nodule was pigmented; dermatoscopy did not yield clarity about whether the lesion was melanocytic. An excisional biopsy with 0.5-cm margins was performed, and histology confirmed that the lesion was a nodular pigmented basal cell carcinoma that had been excised completely.
The case, said Dr. Borges-Costa, shows that skin cancers can develop earlier than the typical 12-18 years after pediatric transplantation. Most reported cases have been squamous cell cancers and melanomas, and often are associated with lack of appropriate sun protection behavior.
The patient, a Caucasian, was a sailor who used sunscreen but did not typically wear a hat while sailing, reported Dr. Borges-Costa, a dermatologist at the University of Lisbon. Her family history was significant for a grandparent with melanoma.
Dr. Borges noted that the parents and patient were given advice regarding the importance of the lifelong use of sun-protective clothing and headgear. “Education of pediatric organ recipients and their parents about sun protection is important because, as occurred with our patient, protective clothing and hats are frequently forgotten.”
Because of the ongoing potential for skin malignancies, early referral “after transplantation to specialized dermatology outpatient clinics, similar to what is now advocated for transplanted adults, could help in surveillance and improve adherence to sun-protective measures,” he added.
SOURCE: Borges-Costa J et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13537..
A 17-year-old girl seen in a Portuguese dermatology clinic was found to have a nodular basal cell carcinoma on the parietal region of her scalp. The nodule appeared 6 years after she had received a kidney transplant, according to João Borges-Costa, MD, PhD, who submitted the case report.
Since the transplant, the girl had been maintained on immunosuppressive medication of tacrolimus 1 mg twice daily, mycophenolate sodium 360 mg twice daily, and prednisolone 10 mg every other day. The 1-cm nodule was pigmented; dermatoscopy did not yield clarity about whether the lesion was melanocytic. An excisional biopsy with 0.5-cm margins was performed, and histology confirmed that the lesion was a nodular pigmented basal cell carcinoma that had been excised completely.
The case, said Dr. Borges-Costa, shows that skin cancers can develop earlier than the typical 12-18 years after pediatric transplantation. Most reported cases have been squamous cell cancers and melanomas, and often are associated with lack of appropriate sun protection behavior.
The patient, a Caucasian, was a sailor who used sunscreen but did not typically wear a hat while sailing, reported Dr. Borges-Costa, a dermatologist at the University of Lisbon. Her family history was significant for a grandparent with melanoma.
Dr. Borges noted that the parents and patient were given advice regarding the importance of the lifelong use of sun-protective clothing and headgear. “Education of pediatric organ recipients and their parents about sun protection is important because, as occurred with our patient, protective clothing and hats are frequently forgotten.”
Because of the ongoing potential for skin malignancies, early referral “after transplantation to specialized dermatology outpatient clinics, similar to what is now advocated for transplanted adults, could help in surveillance and improve adherence to sun-protective measures,” he added.
SOURCE: Borges-Costa J et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13537..
A 17-year-old girl seen in a Portuguese dermatology clinic was found to have a nodular basal cell carcinoma on the parietal region of her scalp. The nodule appeared 6 years after she had received a kidney transplant, according to João Borges-Costa, MD, PhD, who submitted the case report.
Since the transplant, the girl had been maintained on immunosuppressive medication of tacrolimus 1 mg twice daily, mycophenolate sodium 360 mg twice daily, and prednisolone 10 mg every other day. The 1-cm nodule was pigmented; dermatoscopy did not yield clarity about whether the lesion was melanocytic. An excisional biopsy with 0.5-cm margins was performed, and histology confirmed that the lesion was a nodular pigmented basal cell carcinoma that had been excised completely.
The case, said Dr. Borges-Costa, shows that skin cancers can develop earlier than the typical 12-18 years after pediatric transplantation. Most reported cases have been squamous cell cancers and melanomas, and often are associated with lack of appropriate sun protection behavior.
The patient, a Caucasian, was a sailor who used sunscreen but did not typically wear a hat while sailing, reported Dr. Borges-Costa, a dermatologist at the University of Lisbon. Her family history was significant for a grandparent with melanoma.
Dr. Borges noted that the parents and patient were given advice regarding the importance of the lifelong use of sun-protective clothing and headgear. “Education of pediatric organ recipients and their parents about sun protection is important because, as occurred with our patient, protective clothing and hats are frequently forgotten.”
Because of the ongoing potential for skin malignancies, early referral “after transplantation to specialized dermatology outpatient clinics, similar to what is now advocated for transplanted adults, could help in surveillance and improve adherence to sun-protective measures,” he added.
SOURCE: Borges-Costa J et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13537..
FROM PEDIATRIC DERMATOLOGY
Sunscreen use in grade schoolers: Wide racial, ethnic disparities seen
and the figures were much lower for non-Hispanic black children.
Just 23% of fifth graders almost always used sunscreen, according to data drawn from the Healthy Passages study, which surveyed the parents or caregivers of 5,119 fifth graders. That figure was similar in the 1,802 Hispanic respondents, but fell to just 6% of the 1,748 non-Hispanic black respondents.
Some other factors that were associated with less chance of adherence to sunscreen use included being male and having lower socioeconomic status, wrote Christina M. Correnti, MD, and her study coauthors. The report was published in in Pediatric Dermatology. Perhaps surprisingly, they said, “School-based sun-safety education and involvement in team sports were not significant factors.”
Healthy Passages is a prospective multisite cohort study of child and adolescent health. Dr. Correnti, a dermatology resident at the University of Maryland, Baltimore, and her colleagues used baseline Healthy Passages data collected from the period of 2004-2006. Children enrolled in fifth grade at public schools in Birmingham, Ala., Houston, and Los Angeles, together with their caregivers, participated in the survey. Deidentified demographic data were collected, and participants were asked about four preventive health behaviors in addition to sunscreen use and flossing teeth: brushing teeth, helmet use, seatbelt use, and well-child examinations.
Dr. Correnti and her colleagues used multivariable analysis to calculate odds ratios for the association between the various demographic factors and other preventive behaviors and sunscreen use. They found that sunscreen adherence was correlated with all other preventive behaviors (P less than .001), but that the interrelationship with helmet use was confounded by racial and ethnic variables. Seatbelt use was not significantly correlated with sunscreen use for non-Hispanic black or Hispanic respondents.
“Children from more-educated and affluent households were more likely to use sun protection. Perhaps they had greater parental awareness and practice of sun safe habits,” wrote Dr. Correnti and her colleagues, noting that other work has shown that even low-income parents generally don’t see the cost of sunscreen as a barrier to use.
Although overall use of sunscreen among non-Hispanic black children was low, both non-Hispanic black and Hispanic children were more likely to use sunscreen if they had three or more sunburns within the prior 12 months. “Although darker skin tones may afford some sun protection, melanoma incidence is growing in Hispanic populations,” the researchers wrote.
To address these overall low rates of sunscreen use, the investigators discussed the utility of a variety of education options. The well-child visit affords an opportunity to reinforce the importance of preventive behaviors, but physicians may run into a time crunch and forgo thorough sun safety education, they said. Written materials can be a useful adjunct for clinicians in this setting.
“Health care practitioners may use absence of other preventive behaviors as potential markers for inadequate sunscreen use, prompting a point-of-care sun-safety intervention,” they suggested.
A school-based public health approach offers another route for education. “School sun-safety programs may alleviate the primary care burden,” wrote Dr. Correnti and her coinvestigators. The opportunity to deliver repeated, age-tailored messages as children progress through school may be effective in promoting healthy sun behaviors. Messaging that focuses on the negative effects of sun exposure on appearance such as age spots and wrinkles have been more effective than those warning of the risk of skin cancer for teens; investigating appearance-based content for this age group might be a good idea, the authors said.
The fact that the survey sites were in southern cities may mean that national rates of consistent sunscreen use for elementary schoolers may be even lower, said Dr. Correnti and her coauthors. Many other real-world factors, such as frequency and amount of sunscreen applied and the use of sun-protective clothing, couldn’t be captured by the survey, they acknowledged.
“Even in the most adherent group, non-Hispanic whites, only 44.8% always used sunscreen,” the researchers wrote. The study’s findings leave plenty of room for implementation of broad-based programs, especially in low-resource communities.
The National Institutes of Health funded the research. Dr. Correnti was supported by NIH awards.
SOURCE: Correnti CM et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13550.
and the figures were much lower for non-Hispanic black children.
Just 23% of fifth graders almost always used sunscreen, according to data drawn from the Healthy Passages study, which surveyed the parents or caregivers of 5,119 fifth graders. That figure was similar in the 1,802 Hispanic respondents, but fell to just 6% of the 1,748 non-Hispanic black respondents.
Some other factors that were associated with less chance of adherence to sunscreen use included being male and having lower socioeconomic status, wrote Christina M. Correnti, MD, and her study coauthors. The report was published in in Pediatric Dermatology. Perhaps surprisingly, they said, “School-based sun-safety education and involvement in team sports were not significant factors.”
Healthy Passages is a prospective multisite cohort study of child and adolescent health. Dr. Correnti, a dermatology resident at the University of Maryland, Baltimore, and her colleagues used baseline Healthy Passages data collected from the period of 2004-2006. Children enrolled in fifth grade at public schools in Birmingham, Ala., Houston, and Los Angeles, together with their caregivers, participated in the survey. Deidentified demographic data were collected, and participants were asked about four preventive health behaviors in addition to sunscreen use and flossing teeth: brushing teeth, helmet use, seatbelt use, and well-child examinations.
Dr. Correnti and her colleagues used multivariable analysis to calculate odds ratios for the association between the various demographic factors and other preventive behaviors and sunscreen use. They found that sunscreen adherence was correlated with all other preventive behaviors (P less than .001), but that the interrelationship with helmet use was confounded by racial and ethnic variables. Seatbelt use was not significantly correlated with sunscreen use for non-Hispanic black or Hispanic respondents.
“Children from more-educated and affluent households were more likely to use sun protection. Perhaps they had greater parental awareness and practice of sun safe habits,” wrote Dr. Correnti and her colleagues, noting that other work has shown that even low-income parents generally don’t see the cost of sunscreen as a barrier to use.
Although overall use of sunscreen among non-Hispanic black children was low, both non-Hispanic black and Hispanic children were more likely to use sunscreen if they had three or more sunburns within the prior 12 months. “Although darker skin tones may afford some sun protection, melanoma incidence is growing in Hispanic populations,” the researchers wrote.
To address these overall low rates of sunscreen use, the investigators discussed the utility of a variety of education options. The well-child visit affords an opportunity to reinforce the importance of preventive behaviors, but physicians may run into a time crunch and forgo thorough sun safety education, they said. Written materials can be a useful adjunct for clinicians in this setting.
“Health care practitioners may use absence of other preventive behaviors as potential markers for inadequate sunscreen use, prompting a point-of-care sun-safety intervention,” they suggested.
A school-based public health approach offers another route for education. “School sun-safety programs may alleviate the primary care burden,” wrote Dr. Correnti and her coinvestigators. The opportunity to deliver repeated, age-tailored messages as children progress through school may be effective in promoting healthy sun behaviors. Messaging that focuses on the negative effects of sun exposure on appearance such as age spots and wrinkles have been more effective than those warning of the risk of skin cancer for teens; investigating appearance-based content for this age group might be a good idea, the authors said.
The fact that the survey sites were in southern cities may mean that national rates of consistent sunscreen use for elementary schoolers may be even lower, said Dr. Correnti and her coauthors. Many other real-world factors, such as frequency and amount of sunscreen applied and the use of sun-protective clothing, couldn’t be captured by the survey, they acknowledged.
“Even in the most adherent group, non-Hispanic whites, only 44.8% always used sunscreen,” the researchers wrote. The study’s findings leave plenty of room for implementation of broad-based programs, especially in low-resource communities.
The National Institutes of Health funded the research. Dr. Correnti was supported by NIH awards.
SOURCE: Correnti CM et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13550.
and the figures were much lower for non-Hispanic black children.
Just 23% of fifth graders almost always used sunscreen, according to data drawn from the Healthy Passages study, which surveyed the parents or caregivers of 5,119 fifth graders. That figure was similar in the 1,802 Hispanic respondents, but fell to just 6% of the 1,748 non-Hispanic black respondents.
Some other factors that were associated with less chance of adherence to sunscreen use included being male and having lower socioeconomic status, wrote Christina M. Correnti, MD, and her study coauthors. The report was published in in Pediatric Dermatology. Perhaps surprisingly, they said, “School-based sun-safety education and involvement in team sports were not significant factors.”
Healthy Passages is a prospective multisite cohort study of child and adolescent health. Dr. Correnti, a dermatology resident at the University of Maryland, Baltimore, and her colleagues used baseline Healthy Passages data collected from the period of 2004-2006. Children enrolled in fifth grade at public schools in Birmingham, Ala., Houston, and Los Angeles, together with their caregivers, participated in the survey. Deidentified demographic data were collected, and participants were asked about four preventive health behaviors in addition to sunscreen use and flossing teeth: brushing teeth, helmet use, seatbelt use, and well-child examinations.
Dr. Correnti and her colleagues used multivariable analysis to calculate odds ratios for the association between the various demographic factors and other preventive behaviors and sunscreen use. They found that sunscreen adherence was correlated with all other preventive behaviors (P less than .001), but that the interrelationship with helmet use was confounded by racial and ethnic variables. Seatbelt use was not significantly correlated with sunscreen use for non-Hispanic black or Hispanic respondents.
“Children from more-educated and affluent households were more likely to use sun protection. Perhaps they had greater parental awareness and practice of sun safe habits,” wrote Dr. Correnti and her colleagues, noting that other work has shown that even low-income parents generally don’t see the cost of sunscreen as a barrier to use.
Although overall use of sunscreen among non-Hispanic black children was low, both non-Hispanic black and Hispanic children were more likely to use sunscreen if they had three or more sunburns within the prior 12 months. “Although darker skin tones may afford some sun protection, melanoma incidence is growing in Hispanic populations,” the researchers wrote.
To address these overall low rates of sunscreen use, the investigators discussed the utility of a variety of education options. The well-child visit affords an opportunity to reinforce the importance of preventive behaviors, but physicians may run into a time crunch and forgo thorough sun safety education, they said. Written materials can be a useful adjunct for clinicians in this setting.
“Health care practitioners may use absence of other preventive behaviors as potential markers for inadequate sunscreen use, prompting a point-of-care sun-safety intervention,” they suggested.
A school-based public health approach offers another route for education. “School sun-safety programs may alleviate the primary care burden,” wrote Dr. Correnti and her coinvestigators. The opportunity to deliver repeated, age-tailored messages as children progress through school may be effective in promoting healthy sun behaviors. Messaging that focuses on the negative effects of sun exposure on appearance such as age spots and wrinkles have been more effective than those warning of the risk of skin cancer for teens; investigating appearance-based content for this age group might be a good idea, the authors said.
The fact that the survey sites were in southern cities may mean that national rates of consistent sunscreen use for elementary schoolers may be even lower, said Dr. Correnti and her coauthors. Many other real-world factors, such as frequency and amount of sunscreen applied and the use of sun-protective clothing, couldn’t be captured by the survey, they acknowledged.
“Even in the most adherent group, non-Hispanic whites, only 44.8% always used sunscreen,” the researchers wrote. The study’s findings leave plenty of room for implementation of broad-based programs, especially in low-resource communities.
The National Institutes of Health funded the research. Dr. Correnti was supported by NIH awards.
SOURCE: Correnti CM et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13550.
FROM PEDIATRIC DERMATOLOGY
Key clinical point: Most parents surveyed said their children didn’t use sunscreen consistently.
Major finding: Of non-Hispanic black children, 6% almost always used sunscreen.
Study details: Data drawn from Healthy Passages, a prospective cohort study of 5,119 fifth-graders and their parents or caregivers.
Disclosures: The National Institutes of Health funded the research. Dr. Correnti was supported by NIH awards.
Source: Correnti C et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13550.
RISE: Insulin glargine, metformin offer no beta cell function benefit in youth
ORLANDO – in the pediatric medication portion of the Restoring Insulin Secretion (RISE) study.
The treatments, including either metformin for 12 months in 47 participants or insulin glargine for 3 months followed by metformin for 9 months in 44 participants, were not associated with improvement in beta cell function at 12 months, compared with baseline, according to reports from members of the RISE Consortium at the annual scientific sessions of the American Diabetes Association.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Furthermore, measures of beta cell function worsened in both groups at 15-month follow-up, and the same was true for participants with impaired glucose tolerance only; the outcomes in that subset of patients were similar to the entire group, including patients with early T2DM.
“Beta cell failure progressed despite that intervention, and though both [metformin and insulin glargine] were effective for lowering glucose – and metformin for lowering weight ... it had nothing to do with the natural history of the disease, and that’s really quite disappointing,” John B. Buse, MD, said in a video interview.
But that’s not to say the findings weren’t of value.
“The exciting bit was our greater understanding of what’s different about diabetes in youth, and basically [the findings] showed that, both in the setting of impaired glucose tolerance and early diabetes, youth have more insulin resistance than adults, they have relatively more well-preserved beta cell function – they’re secreting more insulin at both impaired glucose tolerance and diabetes, and they have lesser hepatic insulin clearance,” said Dr. Buse, professor, chief of the division of endocrinology, and director of the Diabetes Center at the University of North Carolina, Chapel Hill.
Dr. Buse provided invited commentary on the findings at the ADA scientific sessions and elaborated on those comments in this interview, noting that, in addition to identifying important differences between children and adults with impaired glucose tolerance and diabetes, the RISE study demonstrated that the numerous challenges associated with conducting a major study involving children with impaired glucose tolerance or T2DM can be overcome.
“It’s a really heartwarming story,” he said of the efforts and successes of the RISE investigators in completing the pediatric medication portion of the study. “It at least gives us hope that, even if we haven’t found a cure for type 2 diabetes in children, we at least know we can do the studies.”
Dr. Buse also provided his take on what the future holds for both parts of the RISE study (findings from the adult medication and adult surgery portions are expected to be reported within the next year) and for other studies in children and youth with diabetes; he noted that the current findings and successes in enrolling and completing the pediatric portion of the study highlight multiple opportunities for future research.
Dr. Buse reported financial relationships with Adocia, AstraZeneca, Dexcom, Elcelyx, Eli Lilly, Fractyl Laboratories, Intarcia Therapeutics, Lexicon Pharmaceuticals, Metavention, NovaTarg Therapeutics, Novo Nordisk, Sanofi, VTV Therapeutics, Boehringer Ingelheim, Johnson & Johnson Services, Theracos, Shenzhen Hightide Biopharmaceutical, National Heart Lung and Blood Institute, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association, Patient-Centered Outcomes Research Institute, and the National Institute of Environmental Health Sciences.
ORLANDO – in the pediatric medication portion of the Restoring Insulin Secretion (RISE) study.
The treatments, including either metformin for 12 months in 47 participants or insulin glargine for 3 months followed by metformin for 9 months in 44 participants, were not associated with improvement in beta cell function at 12 months, compared with baseline, according to reports from members of the RISE Consortium at the annual scientific sessions of the American Diabetes Association.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Furthermore, measures of beta cell function worsened in both groups at 15-month follow-up, and the same was true for participants with impaired glucose tolerance only; the outcomes in that subset of patients were similar to the entire group, including patients with early T2DM.
“Beta cell failure progressed despite that intervention, and though both [metformin and insulin glargine] were effective for lowering glucose – and metformin for lowering weight ... it had nothing to do with the natural history of the disease, and that’s really quite disappointing,” John B. Buse, MD, said in a video interview.
But that’s not to say the findings weren’t of value.
“The exciting bit was our greater understanding of what’s different about diabetes in youth, and basically [the findings] showed that, both in the setting of impaired glucose tolerance and early diabetes, youth have more insulin resistance than adults, they have relatively more well-preserved beta cell function – they’re secreting more insulin at both impaired glucose tolerance and diabetes, and they have lesser hepatic insulin clearance,” said Dr. Buse, professor, chief of the division of endocrinology, and director of the Diabetes Center at the University of North Carolina, Chapel Hill.
Dr. Buse provided invited commentary on the findings at the ADA scientific sessions and elaborated on those comments in this interview, noting that, in addition to identifying important differences between children and adults with impaired glucose tolerance and diabetes, the RISE study demonstrated that the numerous challenges associated with conducting a major study involving children with impaired glucose tolerance or T2DM can be overcome.
“It’s a really heartwarming story,” he said of the efforts and successes of the RISE investigators in completing the pediatric medication portion of the study. “It at least gives us hope that, even if we haven’t found a cure for type 2 diabetes in children, we at least know we can do the studies.”
Dr. Buse also provided his take on what the future holds for both parts of the RISE study (findings from the adult medication and adult surgery portions are expected to be reported within the next year) and for other studies in children and youth with diabetes; he noted that the current findings and successes in enrolling and completing the pediatric portion of the study highlight multiple opportunities for future research.
Dr. Buse reported financial relationships with Adocia, AstraZeneca, Dexcom, Elcelyx, Eli Lilly, Fractyl Laboratories, Intarcia Therapeutics, Lexicon Pharmaceuticals, Metavention, NovaTarg Therapeutics, Novo Nordisk, Sanofi, VTV Therapeutics, Boehringer Ingelheim, Johnson & Johnson Services, Theracos, Shenzhen Hightide Biopharmaceutical, National Heart Lung and Blood Institute, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association, Patient-Centered Outcomes Research Institute, and the National Institute of Environmental Health Sciences.
ORLANDO – in the pediatric medication portion of the Restoring Insulin Secretion (RISE) study.
The treatments, including either metformin for 12 months in 47 participants or insulin glargine for 3 months followed by metformin for 9 months in 44 participants, were not associated with improvement in beta cell function at 12 months, compared with baseline, according to reports from members of the RISE Consortium at the annual scientific sessions of the American Diabetes Association.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Furthermore, measures of beta cell function worsened in both groups at 15-month follow-up, and the same was true for participants with impaired glucose tolerance only; the outcomes in that subset of patients were similar to the entire group, including patients with early T2DM.
“Beta cell failure progressed despite that intervention, and though both [metformin and insulin glargine] were effective for lowering glucose – and metformin for lowering weight ... it had nothing to do with the natural history of the disease, and that’s really quite disappointing,” John B. Buse, MD, said in a video interview.
But that’s not to say the findings weren’t of value.
“The exciting bit was our greater understanding of what’s different about diabetes in youth, and basically [the findings] showed that, both in the setting of impaired glucose tolerance and early diabetes, youth have more insulin resistance than adults, they have relatively more well-preserved beta cell function – they’re secreting more insulin at both impaired glucose tolerance and diabetes, and they have lesser hepatic insulin clearance,” said Dr. Buse, professor, chief of the division of endocrinology, and director of the Diabetes Center at the University of North Carolina, Chapel Hill.
Dr. Buse provided invited commentary on the findings at the ADA scientific sessions and elaborated on those comments in this interview, noting that, in addition to identifying important differences between children and adults with impaired glucose tolerance and diabetes, the RISE study demonstrated that the numerous challenges associated with conducting a major study involving children with impaired glucose tolerance or T2DM can be overcome.
“It’s a really heartwarming story,” he said of the efforts and successes of the RISE investigators in completing the pediatric medication portion of the study. “It at least gives us hope that, even if we haven’t found a cure for type 2 diabetes in children, we at least know we can do the studies.”
Dr. Buse also provided his take on what the future holds for both parts of the RISE study (findings from the adult medication and adult surgery portions are expected to be reported within the next year) and for other studies in children and youth with diabetes; he noted that the current findings and successes in enrolling and completing the pediatric portion of the study highlight multiple opportunities for future research.
Dr. Buse reported financial relationships with Adocia, AstraZeneca, Dexcom, Elcelyx, Eli Lilly, Fractyl Laboratories, Intarcia Therapeutics, Lexicon Pharmaceuticals, Metavention, NovaTarg Therapeutics, Novo Nordisk, Sanofi, VTV Therapeutics, Boehringer Ingelheim, Johnson & Johnson Services, Theracos, Shenzhen Hightide Biopharmaceutical, National Heart Lung and Blood Institute, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association, Patient-Centered Outcomes Research Institute, and the National Institute of Environmental Health Sciences.
EXPERT ANALYSIS AT ADA 2018
Uric acid tied to pediatric diabetic kidney disease
ORLANDO – , according to a 7-year investigation of 539 children.
Every 1-mg/dL climb in baseline serum uric acid increased the risk of subsequent elevated urine albumin excretion 1.23 fold, after adjustment for potential confounders (P = .02).
The finding adds to growing evidence that serum uric acid (SUA) isn’t just a marker of diabetic kidney disease, but a contributor to it. “There is definitely” cross-talk between gout and diabetes, said lead investigator Petter Bjornstad, MD, assistant professor of pediatric endocrinology at the University of Colorado, Aurora.
Elevated SUA is common in both conditions and a risk factor for kidney disease. Newer studies have linked higher levels to nephron number decline and other pathologies, perhaps through renal inflammation. Allopurinol, the traditional uric acid lowering agent in gout, is already under investigation to prevent kidney decline in adults with type 1 diabetes mellitus. There’s also evidence that the potent uric acid lowering agent, febuxostat (Uloric), attenuates hypofiltration in early diabetic kidney disease.
The 539 children, all part of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial, were assessed annually over a mean of 5.7 years. At baseline, they were 13.9 years old and had T2DM for 7.9 months, on average. The mean body mass index was 34.6 kg/m2, mean hemoglobin A1c was 6%.
Almost 20% of the children were hypertensive at baseline (130/80 mm Hg or higher); 26% were hyperuricemic (6.8 mg/dL or higher); and 6.1% had elevated urine albumin excretion (urine albumin creatinine ratio of at least 30 mg/g), a marker of renal pathology. At the end of follow-up, 18% had elevated albumin excretion and 37.4% were hypertensive.
“Hyperuricemia was common in youth with type 2 diabetes,” just as it’s been shown in adults with the disease. “Higher baseline SUA independently increase[s] risk for onset of hypertension and elevated urine albumin excretion,” Dr. Bjornstad said.
However, the association between SUA and elevated albumin excretion was statistically significant only in boys – 36% of the study population – and non-Hispanic whites, 20% of the subjects, after adjustment for BMI, hemoglobin A1c, estimated glomerular filtration rate, and use of ACE inhibitors and angiotensin II receptor blockers.
The National Institutes of Health funded the work. Dr. Bjornstad is a consultant for Boehringer Ingelheim.
SOURCE: Bjornstad P et al. ADA 2018, abstract 339-OR.
ORLANDO – , according to a 7-year investigation of 539 children.
Every 1-mg/dL climb in baseline serum uric acid increased the risk of subsequent elevated urine albumin excretion 1.23 fold, after adjustment for potential confounders (P = .02).
The finding adds to growing evidence that serum uric acid (SUA) isn’t just a marker of diabetic kidney disease, but a contributor to it. “There is definitely” cross-talk between gout and diabetes, said lead investigator Petter Bjornstad, MD, assistant professor of pediatric endocrinology at the University of Colorado, Aurora.
Elevated SUA is common in both conditions and a risk factor for kidney disease. Newer studies have linked higher levels to nephron number decline and other pathologies, perhaps through renal inflammation. Allopurinol, the traditional uric acid lowering agent in gout, is already under investigation to prevent kidney decline in adults with type 1 diabetes mellitus. There’s also evidence that the potent uric acid lowering agent, febuxostat (Uloric), attenuates hypofiltration in early diabetic kidney disease.
The 539 children, all part of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial, were assessed annually over a mean of 5.7 years. At baseline, they were 13.9 years old and had T2DM for 7.9 months, on average. The mean body mass index was 34.6 kg/m2, mean hemoglobin A1c was 6%.
Almost 20% of the children were hypertensive at baseline (130/80 mm Hg or higher); 26% were hyperuricemic (6.8 mg/dL or higher); and 6.1% had elevated urine albumin excretion (urine albumin creatinine ratio of at least 30 mg/g), a marker of renal pathology. At the end of follow-up, 18% had elevated albumin excretion and 37.4% were hypertensive.
“Hyperuricemia was common in youth with type 2 diabetes,” just as it’s been shown in adults with the disease. “Higher baseline SUA independently increase[s] risk for onset of hypertension and elevated urine albumin excretion,” Dr. Bjornstad said.
However, the association between SUA and elevated albumin excretion was statistically significant only in boys – 36% of the study population – and non-Hispanic whites, 20% of the subjects, after adjustment for BMI, hemoglobin A1c, estimated glomerular filtration rate, and use of ACE inhibitors and angiotensin II receptor blockers.
The National Institutes of Health funded the work. Dr. Bjornstad is a consultant for Boehringer Ingelheim.
SOURCE: Bjornstad P et al. ADA 2018, abstract 339-OR.
ORLANDO – , according to a 7-year investigation of 539 children.
Every 1-mg/dL climb in baseline serum uric acid increased the risk of subsequent elevated urine albumin excretion 1.23 fold, after adjustment for potential confounders (P = .02).
The finding adds to growing evidence that serum uric acid (SUA) isn’t just a marker of diabetic kidney disease, but a contributor to it. “There is definitely” cross-talk between gout and diabetes, said lead investigator Petter Bjornstad, MD, assistant professor of pediatric endocrinology at the University of Colorado, Aurora.
Elevated SUA is common in both conditions and a risk factor for kidney disease. Newer studies have linked higher levels to nephron number decline and other pathologies, perhaps through renal inflammation. Allopurinol, the traditional uric acid lowering agent in gout, is already under investigation to prevent kidney decline in adults with type 1 diabetes mellitus. There’s also evidence that the potent uric acid lowering agent, febuxostat (Uloric), attenuates hypofiltration in early diabetic kidney disease.
The 539 children, all part of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial, were assessed annually over a mean of 5.7 years. At baseline, they were 13.9 years old and had T2DM for 7.9 months, on average. The mean body mass index was 34.6 kg/m2, mean hemoglobin A1c was 6%.
Almost 20% of the children were hypertensive at baseline (130/80 mm Hg or higher); 26% were hyperuricemic (6.8 mg/dL or higher); and 6.1% had elevated urine albumin excretion (urine albumin creatinine ratio of at least 30 mg/g), a marker of renal pathology. At the end of follow-up, 18% had elevated albumin excretion and 37.4% were hypertensive.
“Hyperuricemia was common in youth with type 2 diabetes,” just as it’s been shown in adults with the disease. “Higher baseline SUA independently increase[s] risk for onset of hypertension and elevated urine albumin excretion,” Dr. Bjornstad said.
However, the association between SUA and elevated albumin excretion was statistically significant only in boys – 36% of the study population – and non-Hispanic whites, 20% of the subjects, after adjustment for BMI, hemoglobin A1c, estimated glomerular filtration rate, and use of ACE inhibitors and angiotensin II receptor blockers.
The National Institutes of Health funded the work. Dr. Bjornstad is a consultant for Boehringer Ingelheim.
SOURCE: Bjornstad P et al. ADA 2018, abstract 339-OR.
REPORTING FROM ADA 2018
Key clinical point: Serum uric acid lowering might help prevent kidney disease in children with T2DM.
Major finding: Every1-mg/dL climb in baseline serum uric acid increased the risk of subsequent elevated urine albumin excretion 1.23 fold, after adjustment for potential confounders (P = .02)
Study details: Seven-year investigation of 539 children with new-onset T2DM.
Disclosures: The National Institutes of Health funded the work. The study lead is a consultant for Boehringer Ingelheim.
Source: Bjornstad P et al. ADA 2018 Abstract 339-OR.
Pediatric dermatology admissions: Crunching the numbers
according to data from the Agency for Healthcare Research and Quality.
There were 74,229 such admissions in the United States that year – all others totaled 1.77 million – and the children at the highest risk for dermatology hospitalization were those living in communities with the lowest household incomes, the uninsured and those on Medicaid, and those living in the South, Justin D. Arnold of George Washington University, Washington, and his associates said in Pediatric Dermatology.
“Individuals from communities of low socioeconomic status may be more likely to be hospitalized because of gaps in insurance coverage, difficulty with transportation, or inconsistent access to preventative medical care, which for skin disease, would include access to an outpatient pediatric dermatologist,” they wrote.
All those admissions for skin diseases cost the health care system $379.8 million in 2012, or 1.9% of the $20.3 billion spent on all pediatric hospitalizations, excluding those related to pregnancy or childbirth. The mean cost of a skin disease admission was $5,211 for a child aged less than 18 years, compared with $11,409 for nondermatology admissions, according to data from the 2012 Kids’ Inpatient Database, which includes records of pediatric discharges from 44 states.
Cutaneous lymphoma was the most expensive skin disease per admission at a mean cost of $58,294, with congenital skin abnormalities second at $24,186, and ulcers third at $17,064. Bacterial skin infections and infestations were only the 19th most expensive admission at $4,135, but it was by far the most common (59,115 admissions) and the most expensive overall, with a total cost of $240 million. The second most common condition was viral diseases with 3,812 admissions and the next most expensive total was $33.5 million for connective tissue disorders, Mr. Arnold and his associates said.
Multivariate models that adjusted for such factors as age, sex, and race revealed that “the risk of hospitalization for skin disease increased as the median income of one’s zip code declined,” the investigators noted. The adjusted odds ratio for hospitalization in the lowest-income quartile (less than $39,000) was 1.22, compared with the highest-income quartile.
Insurance status also affected hospitalization, putting children from families with no insurance (aOR, 1.35) and those on Medicaid (aOR, 1.17) at a disadvantage, compared with those who had private insurance. “Policy makers should consider increasing Medicaid reimbursement rates to outpatient dermatologists, which might encourage more clinicians to accept this form of insurance and thereby expand access to preventative skin care,” they said.
Regional differences also were observed, which put children from the southern states at the highest risk (aOR, 1.32), compared with those in the West, which could be related to access issues. “In 2016, 4 of the 10 communities in the United States with the lowest density of dermatologists were in the South, suggesting that the high rate of hospitalizations there may also be partially attributed to lack of access to dermatologists,” Mr. Arnold and his associates wrote.
The investigators did not report funding or disclose conflicts of interest.
SOURCE: Arnold JD et al. Pediatr Dermatol. 2018 Jul 1. doi: 10.1111/pde.13549.
according to data from the Agency for Healthcare Research and Quality.
There were 74,229 such admissions in the United States that year – all others totaled 1.77 million – and the children at the highest risk for dermatology hospitalization were those living in communities with the lowest household incomes, the uninsured and those on Medicaid, and those living in the South, Justin D. Arnold of George Washington University, Washington, and his associates said in Pediatric Dermatology.
“Individuals from communities of low socioeconomic status may be more likely to be hospitalized because of gaps in insurance coverage, difficulty with transportation, or inconsistent access to preventative medical care, which for skin disease, would include access to an outpatient pediatric dermatologist,” they wrote.
All those admissions for skin diseases cost the health care system $379.8 million in 2012, or 1.9% of the $20.3 billion spent on all pediatric hospitalizations, excluding those related to pregnancy or childbirth. The mean cost of a skin disease admission was $5,211 for a child aged less than 18 years, compared with $11,409 for nondermatology admissions, according to data from the 2012 Kids’ Inpatient Database, which includes records of pediatric discharges from 44 states.
Cutaneous lymphoma was the most expensive skin disease per admission at a mean cost of $58,294, with congenital skin abnormalities second at $24,186, and ulcers third at $17,064. Bacterial skin infections and infestations were only the 19th most expensive admission at $4,135, but it was by far the most common (59,115 admissions) and the most expensive overall, with a total cost of $240 million. The second most common condition was viral diseases with 3,812 admissions and the next most expensive total was $33.5 million for connective tissue disorders, Mr. Arnold and his associates said.
Multivariate models that adjusted for such factors as age, sex, and race revealed that “the risk of hospitalization for skin disease increased as the median income of one’s zip code declined,” the investigators noted. The adjusted odds ratio for hospitalization in the lowest-income quartile (less than $39,000) was 1.22, compared with the highest-income quartile.
Insurance status also affected hospitalization, putting children from families with no insurance (aOR, 1.35) and those on Medicaid (aOR, 1.17) at a disadvantage, compared with those who had private insurance. “Policy makers should consider increasing Medicaid reimbursement rates to outpatient dermatologists, which might encourage more clinicians to accept this form of insurance and thereby expand access to preventative skin care,” they said.
Regional differences also were observed, which put children from the southern states at the highest risk (aOR, 1.32), compared with those in the West, which could be related to access issues. “In 2016, 4 of the 10 communities in the United States with the lowest density of dermatologists were in the South, suggesting that the high rate of hospitalizations there may also be partially attributed to lack of access to dermatologists,” Mr. Arnold and his associates wrote.
The investigators did not report funding or disclose conflicts of interest.
SOURCE: Arnold JD et al. Pediatr Dermatol. 2018 Jul 1. doi: 10.1111/pde.13549.
according to data from the Agency for Healthcare Research and Quality.
There were 74,229 such admissions in the United States that year – all others totaled 1.77 million – and the children at the highest risk for dermatology hospitalization were those living in communities with the lowest household incomes, the uninsured and those on Medicaid, and those living in the South, Justin D. Arnold of George Washington University, Washington, and his associates said in Pediatric Dermatology.
“Individuals from communities of low socioeconomic status may be more likely to be hospitalized because of gaps in insurance coverage, difficulty with transportation, or inconsistent access to preventative medical care, which for skin disease, would include access to an outpatient pediatric dermatologist,” they wrote.
All those admissions for skin diseases cost the health care system $379.8 million in 2012, or 1.9% of the $20.3 billion spent on all pediatric hospitalizations, excluding those related to pregnancy or childbirth. The mean cost of a skin disease admission was $5,211 for a child aged less than 18 years, compared with $11,409 for nondermatology admissions, according to data from the 2012 Kids’ Inpatient Database, which includes records of pediatric discharges from 44 states.
Cutaneous lymphoma was the most expensive skin disease per admission at a mean cost of $58,294, with congenital skin abnormalities second at $24,186, and ulcers third at $17,064. Bacterial skin infections and infestations were only the 19th most expensive admission at $4,135, but it was by far the most common (59,115 admissions) and the most expensive overall, with a total cost of $240 million. The second most common condition was viral diseases with 3,812 admissions and the next most expensive total was $33.5 million for connective tissue disorders, Mr. Arnold and his associates said.
Multivariate models that adjusted for such factors as age, sex, and race revealed that “the risk of hospitalization for skin disease increased as the median income of one’s zip code declined,” the investigators noted. The adjusted odds ratio for hospitalization in the lowest-income quartile (less than $39,000) was 1.22, compared with the highest-income quartile.
Insurance status also affected hospitalization, putting children from families with no insurance (aOR, 1.35) and those on Medicaid (aOR, 1.17) at a disadvantage, compared with those who had private insurance. “Policy makers should consider increasing Medicaid reimbursement rates to outpatient dermatologists, which might encourage more clinicians to accept this form of insurance and thereby expand access to preventative skin care,” they said.
Regional differences also were observed, which put children from the southern states at the highest risk (aOR, 1.32), compared with those in the West, which could be related to access issues. “In 2016, 4 of the 10 communities in the United States with the lowest density of dermatologists were in the South, suggesting that the high rate of hospitalizations there may also be partially attributed to lack of access to dermatologists,” Mr. Arnold and his associates wrote.
The investigators did not report funding or disclose conflicts of interest.
SOURCE: Arnold JD et al. Pediatr Dermatol. 2018 Jul 1. doi: 10.1111/pde.13549.
FROM PEDIATRIC DERMATOLOGY
Key clinical point: Children at the highest risk for dermatology hospitalization lived in communities with the lowest household incomes, were uninsured or on Medicaid, or lived in the South.
Major finding: Admissions for skin diseases cost $379.8 million in 2012, or 1.9% of all spending on pediatric hospitalizations.
Study details: A statistical analysis of the 2012 Kids’ Inpatient Database.
Disclosures: The investigators did not report funding or disclose conflicts of interest.
Source: Arnold JD et al. Pediatr Dermatol. 2018 Jul 1. doi: 10.1111/pde.13549.
Study spotlights risk factors for albuminuria in youth with T2DM
TORONTO – When Brandy Wicklow, MD, began her pediatric endocrinology fellowship at McGill University in 2006, about 12 per 100,000 children in Manitoba, Canada, were diagnosed with type 2 diabetes mellitus each year. By 2016 that rate had more than doubled, to 26 per 100,000 children.
“If you look just at indigenous youth in our province, it’s probably one of the highest rates ever reported, with 95 per 100,000 Manitoba First Nation children diagnosed with type 2 diabetes,” said Dr. Wicklow, a pediatric endocrinologist at the University of Manitoba and the Children’s Hospital Research Institute of Manitoba.
Many indigenous populations also face an increased risk for primary renal disease. One study reviewed the charts 90 of Canadian First Nation children and adolescents with T2DM (Diabetes Care. 2009;32[5]:786-90). Of 10 who had renal biopsies performed, nine had immune complex disease/glomerulosclerosis, two had mild diabetes-related lesions, and seven had focal segmental glomerulosclerosis (FSGS); yet none had classic nephropathy. An analysis of Chinese youth that included 216 renal biopsies yielded similar findings (Intl Urol Nephrol. 2012;45[1]:173-9).
It’s also known that early-onset T2DM is associated with substantially increased incidence of end-stage renal disease (ESRD) and mortality in middle age. For example, one study of Pima Indians found that those who were diagnosed with T2DM earlier than 20 years of age had a one in five chance of developing ESRD, while those who were diagnosed at age 20 years or older had a one in two chance of ESRD (JAMA. 2006;296[4]:421-6). In a separate analysis, researchers estimated the remaining lifetime risks for ESRD among Aboriginal people in Australia with and without diabetes (Diabetes Res Clin Pract. 2014;103[3]:e24-6). The value for young adults with diabetes was high, about one in two at the age of 30 years, while it decreased with age to one in seven at 60 years.
“One of the first biomarkers we see in terms of renal disease in kids with T2DM is albuminuria,” Dr. Wicklow said at the Pediatric Academic Societies meeting. “The question is, why do kids with type 2 get more renal disease than kids with type 1 diabetes?” The SEARCH for Diabetes in Youth (SEARCH) study from 2006 found that hypertension, increased body mass index, increased weight circumference, and increased lipids were factors, while the SEARCH study from 2015 found that ethnicity, increased weight to height ratio, and mean arterial pressure were factors.
“Insulin resistance is significantly associated with albuminuria,” Dr. Wicklow continued. “It’s also been shown to be associated with hyperfiltration. Some of the markers of insulin resistance are important but they make up about 19% of the variance between type 1 and type 2, which means there are other variables that we’re not measuring.”
Enter ICARE (Improving Renal Complications in Adolescents with Type 2 Diabetes through Research), an ongoing prospective cohort study that Dr. Wicklow and her associates launched in 2014 at eight centers in Canada. It aims to examine the biopsychosocial risk factors for albuminuria in youth with T2DM and the mechanisms for renal injury. “Our theoretical framework was that biological exposures that we are aware of, such as glycemic control, hypertension, and lipids, would all be important in the development of albuminuria and renal disease in kids,” said Dr. Wicklow, who is the study’s coprimary investigator along with Allison Dart, MD. “But what we thought was novel was that psychological exposures either as socioeconomic status or as mental health factors would also directly impinge on renal health with respect to chronic inflammation in the body, inflammation in the kidneys, and long-term kidney damage.”
The first phase of ICARE involved a detailed phenotypic assessment of youth, including anthropometrics, biochemistry, 24-hour ambulatory blood pressure monitoring, overnight urine collections for albumin excretion, renal ultrasound, and iohexol-derived glomerular filtration rate (GFR). Phase 2 included an evaluation of psychological factors, including hair-derived cortisol; validated questionnaires for perceived stress, distress, and resiliency; and a detailed evaluation of systemic and urine inflammatory biomarkers. Annual follow-up is carried out to assess temporal associations between clinical risk factors and renal outcomes, including progression of albuminuria.
At the meeting, Dr. Wicklow reported on 187 youth enrolled to date. Of these, 96% were of indigenous ethnicity, 57 had albuminuria and 130 did not, and the mean ages of the groups were 16 years and 15 years, respectively. At baseline, a higher proportion of those in the albuminuria group were female (74% vs. 64% of those in the no albuminuria group, respectively), had a higher mean hemoglobin A1c (11% vs. 9%), and had hypertension (94% vs. 72%). She noted that upon presentation to the clinic, only 23% of participants had HbA1c levels less than 7%, only 26% had ranges between 7% and 9%, and about 40% did not have any hypertension. Of those who did, 27% had nighttime-only hypertension, and only 2% had daytime-only hypertension.
“The other risk factor these kids have for developing ESRD is that the majority were exposed to diabetes in pregnancy,” Dr. Wicklow said. “Murine models of maternal diabetes exposure have demonstrated that offspring have small kidneys, less ureteric bud branching, and a lower number of nephrons. Most of the human clinical cohort studies look at associations between development of diabetes and parental hypertension, maternal smoking, and maternal education. There is likely an impact at birth that sets these kids up for development of type 2 diabetes.”
In addition, results from clinical cohort studies have found that depression, mental stress, and distress are high in youth with T2DM. “Preliminary data suggest that if you have positive mental health, or coping strategies, or someone has worked through this with you and you are resilient, you might benefit in terms of overall glycemic control,” she said. For example, ICARE investigators have found that the higher the score on the Kessler Psychological Distress Scale (K6), the greater the risk of renal inflammation as measured by monocyte chemotactic protein-1 (MCP-1; P = .02). “Mental health seems to be something that can directly impact your health from a biological standpoint, and we might be able to find biomarkers of that risk,” Dr. Wicklow said. “Where does the stress come from? Most of my patients are indigenous, so it’s not surprising that the history in Canada of colonization of residential schools has left a lasting impression on these families and communities in terms of loss of language, loss of culture, and loss of land. There’s a community-based stress and a family-based stress that these children feel.”
Social factors also play a big role. She presented baseline findings from 196 youth with T2DM and 456 with T1DM, including measures such as the Socioeconomic Factor Index-Version 2 (SEFI-2), a way to assess socioeconomic characteristics based on Canadian Census data that reflects nonmedical social determinants of health. “It looks at factors like number of rooms in the house, single-parent households, maternal education attainment, and family income,” Dr. Wicklow explained. “The higher the SEFI-2 score, the lower your socioeconomic status is for the area you live in. Kids with T2DM generally live in areas of lower SES and lower socioeconomic index. They often live far away from health care providers. Many do not attend school and many are not with their biologic families, so we’ve had a lot of issues addressing child and family services, in particular in the phase of a chronic illness where our expectation is one thing and the family’s and community’s expectations of what’s realistic in terms of treatment and goals is another. We also have a lot of adolescent pregnancies.”
To date, about 80% of youth with T1D have seen a health care provider within the first year after transition from the pediatric diabetes clinic, compared with just over 50% of kids with T2D. “We transition youth with T1DM to internists, while our youth with T2DM go to itinerant physicians often back in their communities and/or rural family physicians,” she said. Between baseline and year 2, the rate of hospital admissions remained similar among T1DM at 11.6 and 11.8 admissions per 100 patient-years, respectively, but the number of hospital admissions for T2DM patients jumped from 20.1 to 25.5 admissions per 100 patient-years. “Kids with type 2 are showing up in the hospital a lot more than those with type 1 diabetes, but not for diabetes-related diagnoses,” Dr. Wicklow said. “We’re starting to look through the data now, and most of our kids are showing up with mental health complaints and issues. That’s why they’re getting hospitalized.”
Among ICARE study participants who have completed 3 years of follow-up, about 52% had albuminuria at their baseline visit and 48% sustained albuminuria throughout the study. About 26% progressed from normal levels of albuminuria to microalbuminuria, from microalbuminuria to macroalbuminuria, or from normal levels of albuminuria to macroalbuminuria. In addition, 16% persisted in the category that they were in, and 10% regressed. “The good news is, some of our kids get better over time,” Dr. Wicklow said. “The bad news is that the majority do not.”
Going forward, Dr. Wicklow and her associates work with an ICARE advisory group composed of children and families “who sit with us and talk about what mental health needs might be important, and how we should organize our study in a follow-up of the kids, to try and answer some of the questions that are important,” she said. “Working with the concept of the study’s theoretical framework, they acknowledged that the biological exposures are important, but they were also concerned about food security, finding strength/resilience within the community, and finding coping factors in terms of keeping themselves healthy with their diabetes. For some communities, they are concerned with basic needs. We’re working with them to help them progress, and to figure out how to best study children with type 2 diabetes.”
ICARE has received support from Diabetes Canada, Research Manitoba, the Canadian Institutes of Health Research, the Children’s Hospital Research Institute of Manitoba (specifically the Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) theme), and the University of Manitoba. Dr. Wicklow reported having no financial disclosures.
TORONTO – When Brandy Wicklow, MD, began her pediatric endocrinology fellowship at McGill University in 2006, about 12 per 100,000 children in Manitoba, Canada, were diagnosed with type 2 diabetes mellitus each year. By 2016 that rate had more than doubled, to 26 per 100,000 children.
“If you look just at indigenous youth in our province, it’s probably one of the highest rates ever reported, with 95 per 100,000 Manitoba First Nation children diagnosed with type 2 diabetes,” said Dr. Wicklow, a pediatric endocrinologist at the University of Manitoba and the Children’s Hospital Research Institute of Manitoba.
Many indigenous populations also face an increased risk for primary renal disease. One study reviewed the charts 90 of Canadian First Nation children and adolescents with T2DM (Diabetes Care. 2009;32[5]:786-90). Of 10 who had renal biopsies performed, nine had immune complex disease/glomerulosclerosis, two had mild diabetes-related lesions, and seven had focal segmental glomerulosclerosis (FSGS); yet none had classic nephropathy. An analysis of Chinese youth that included 216 renal biopsies yielded similar findings (Intl Urol Nephrol. 2012;45[1]:173-9).
It’s also known that early-onset T2DM is associated with substantially increased incidence of end-stage renal disease (ESRD) and mortality in middle age. For example, one study of Pima Indians found that those who were diagnosed with T2DM earlier than 20 years of age had a one in five chance of developing ESRD, while those who were diagnosed at age 20 years or older had a one in two chance of ESRD (JAMA. 2006;296[4]:421-6). In a separate analysis, researchers estimated the remaining lifetime risks for ESRD among Aboriginal people in Australia with and without diabetes (Diabetes Res Clin Pract. 2014;103[3]:e24-6). The value for young adults with diabetes was high, about one in two at the age of 30 years, while it decreased with age to one in seven at 60 years.
“One of the first biomarkers we see in terms of renal disease in kids with T2DM is albuminuria,” Dr. Wicklow said at the Pediatric Academic Societies meeting. “The question is, why do kids with type 2 get more renal disease than kids with type 1 diabetes?” The SEARCH for Diabetes in Youth (SEARCH) study from 2006 found that hypertension, increased body mass index, increased weight circumference, and increased lipids were factors, while the SEARCH study from 2015 found that ethnicity, increased weight to height ratio, and mean arterial pressure were factors.
“Insulin resistance is significantly associated with albuminuria,” Dr. Wicklow continued. “It’s also been shown to be associated with hyperfiltration. Some of the markers of insulin resistance are important but they make up about 19% of the variance between type 1 and type 2, which means there are other variables that we’re not measuring.”
Enter ICARE (Improving Renal Complications in Adolescents with Type 2 Diabetes through Research), an ongoing prospective cohort study that Dr. Wicklow and her associates launched in 2014 at eight centers in Canada. It aims to examine the biopsychosocial risk factors for albuminuria in youth with T2DM and the mechanisms for renal injury. “Our theoretical framework was that biological exposures that we are aware of, such as glycemic control, hypertension, and lipids, would all be important in the development of albuminuria and renal disease in kids,” said Dr. Wicklow, who is the study’s coprimary investigator along with Allison Dart, MD. “But what we thought was novel was that psychological exposures either as socioeconomic status or as mental health factors would also directly impinge on renal health with respect to chronic inflammation in the body, inflammation in the kidneys, and long-term kidney damage.”
The first phase of ICARE involved a detailed phenotypic assessment of youth, including anthropometrics, biochemistry, 24-hour ambulatory blood pressure monitoring, overnight urine collections for albumin excretion, renal ultrasound, and iohexol-derived glomerular filtration rate (GFR). Phase 2 included an evaluation of psychological factors, including hair-derived cortisol; validated questionnaires for perceived stress, distress, and resiliency; and a detailed evaluation of systemic and urine inflammatory biomarkers. Annual follow-up is carried out to assess temporal associations between clinical risk factors and renal outcomes, including progression of albuminuria.
At the meeting, Dr. Wicklow reported on 187 youth enrolled to date. Of these, 96% were of indigenous ethnicity, 57 had albuminuria and 130 did not, and the mean ages of the groups were 16 years and 15 years, respectively. At baseline, a higher proportion of those in the albuminuria group were female (74% vs. 64% of those in the no albuminuria group, respectively), had a higher mean hemoglobin A1c (11% vs. 9%), and had hypertension (94% vs. 72%). She noted that upon presentation to the clinic, only 23% of participants had HbA1c levels less than 7%, only 26% had ranges between 7% and 9%, and about 40% did not have any hypertension. Of those who did, 27% had nighttime-only hypertension, and only 2% had daytime-only hypertension.
“The other risk factor these kids have for developing ESRD is that the majority were exposed to diabetes in pregnancy,” Dr. Wicklow said. “Murine models of maternal diabetes exposure have demonstrated that offspring have small kidneys, less ureteric bud branching, and a lower number of nephrons. Most of the human clinical cohort studies look at associations between development of diabetes and parental hypertension, maternal smoking, and maternal education. There is likely an impact at birth that sets these kids up for development of type 2 diabetes.”
In addition, results from clinical cohort studies have found that depression, mental stress, and distress are high in youth with T2DM. “Preliminary data suggest that if you have positive mental health, or coping strategies, or someone has worked through this with you and you are resilient, you might benefit in terms of overall glycemic control,” she said. For example, ICARE investigators have found that the higher the score on the Kessler Psychological Distress Scale (K6), the greater the risk of renal inflammation as measured by monocyte chemotactic protein-1 (MCP-1; P = .02). “Mental health seems to be something that can directly impact your health from a biological standpoint, and we might be able to find biomarkers of that risk,” Dr. Wicklow said. “Where does the stress come from? Most of my patients are indigenous, so it’s not surprising that the history in Canada of colonization of residential schools has left a lasting impression on these families and communities in terms of loss of language, loss of culture, and loss of land. There’s a community-based stress and a family-based stress that these children feel.”
Social factors also play a big role. She presented baseline findings from 196 youth with T2DM and 456 with T1DM, including measures such as the Socioeconomic Factor Index-Version 2 (SEFI-2), a way to assess socioeconomic characteristics based on Canadian Census data that reflects nonmedical social determinants of health. “It looks at factors like number of rooms in the house, single-parent households, maternal education attainment, and family income,” Dr. Wicklow explained. “The higher the SEFI-2 score, the lower your socioeconomic status is for the area you live in. Kids with T2DM generally live in areas of lower SES and lower socioeconomic index. They often live far away from health care providers. Many do not attend school and many are not with their biologic families, so we’ve had a lot of issues addressing child and family services, in particular in the phase of a chronic illness where our expectation is one thing and the family’s and community’s expectations of what’s realistic in terms of treatment and goals is another. We also have a lot of adolescent pregnancies.”
To date, about 80% of youth with T1D have seen a health care provider within the first year after transition from the pediatric diabetes clinic, compared with just over 50% of kids with T2D. “We transition youth with T1DM to internists, while our youth with T2DM go to itinerant physicians often back in their communities and/or rural family physicians,” she said. Between baseline and year 2, the rate of hospital admissions remained similar among T1DM at 11.6 and 11.8 admissions per 100 patient-years, respectively, but the number of hospital admissions for T2DM patients jumped from 20.1 to 25.5 admissions per 100 patient-years. “Kids with type 2 are showing up in the hospital a lot more than those with type 1 diabetes, but not for diabetes-related diagnoses,” Dr. Wicklow said. “We’re starting to look through the data now, and most of our kids are showing up with mental health complaints and issues. That’s why they’re getting hospitalized.”
Among ICARE study participants who have completed 3 years of follow-up, about 52% had albuminuria at their baseline visit and 48% sustained albuminuria throughout the study. About 26% progressed from normal levels of albuminuria to microalbuminuria, from microalbuminuria to macroalbuminuria, or from normal levels of albuminuria to macroalbuminuria. In addition, 16% persisted in the category that they were in, and 10% regressed. “The good news is, some of our kids get better over time,” Dr. Wicklow said. “The bad news is that the majority do not.”
Going forward, Dr. Wicklow and her associates work with an ICARE advisory group composed of children and families “who sit with us and talk about what mental health needs might be important, and how we should organize our study in a follow-up of the kids, to try and answer some of the questions that are important,” she said. “Working with the concept of the study’s theoretical framework, they acknowledged that the biological exposures are important, but they were also concerned about food security, finding strength/resilience within the community, and finding coping factors in terms of keeping themselves healthy with their diabetes. For some communities, they are concerned with basic needs. We’re working with them to help them progress, and to figure out how to best study children with type 2 diabetes.”
ICARE has received support from Diabetes Canada, Research Manitoba, the Canadian Institutes of Health Research, the Children’s Hospital Research Institute of Manitoba (specifically the Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) theme), and the University of Manitoba. Dr. Wicklow reported having no financial disclosures.
TORONTO – When Brandy Wicklow, MD, began her pediatric endocrinology fellowship at McGill University in 2006, about 12 per 100,000 children in Manitoba, Canada, were diagnosed with type 2 diabetes mellitus each year. By 2016 that rate had more than doubled, to 26 per 100,000 children.
“If you look just at indigenous youth in our province, it’s probably one of the highest rates ever reported, with 95 per 100,000 Manitoba First Nation children diagnosed with type 2 diabetes,” said Dr. Wicklow, a pediatric endocrinologist at the University of Manitoba and the Children’s Hospital Research Institute of Manitoba.
Many indigenous populations also face an increased risk for primary renal disease. One study reviewed the charts 90 of Canadian First Nation children and adolescents with T2DM (Diabetes Care. 2009;32[5]:786-90). Of 10 who had renal biopsies performed, nine had immune complex disease/glomerulosclerosis, two had mild diabetes-related lesions, and seven had focal segmental glomerulosclerosis (FSGS); yet none had classic nephropathy. An analysis of Chinese youth that included 216 renal biopsies yielded similar findings (Intl Urol Nephrol. 2012;45[1]:173-9).
It’s also known that early-onset T2DM is associated with substantially increased incidence of end-stage renal disease (ESRD) and mortality in middle age. For example, one study of Pima Indians found that those who were diagnosed with T2DM earlier than 20 years of age had a one in five chance of developing ESRD, while those who were diagnosed at age 20 years or older had a one in two chance of ESRD (JAMA. 2006;296[4]:421-6). In a separate analysis, researchers estimated the remaining lifetime risks for ESRD among Aboriginal people in Australia with and without diabetes (Diabetes Res Clin Pract. 2014;103[3]:e24-6). The value for young adults with diabetes was high, about one in two at the age of 30 years, while it decreased with age to one in seven at 60 years.
“One of the first biomarkers we see in terms of renal disease in kids with T2DM is albuminuria,” Dr. Wicklow said at the Pediatric Academic Societies meeting. “The question is, why do kids with type 2 get more renal disease than kids with type 1 diabetes?” The SEARCH for Diabetes in Youth (SEARCH) study from 2006 found that hypertension, increased body mass index, increased weight circumference, and increased lipids were factors, while the SEARCH study from 2015 found that ethnicity, increased weight to height ratio, and mean arterial pressure were factors.
“Insulin resistance is significantly associated with albuminuria,” Dr. Wicklow continued. “It’s also been shown to be associated with hyperfiltration. Some of the markers of insulin resistance are important but they make up about 19% of the variance between type 1 and type 2, which means there are other variables that we’re not measuring.”
Enter ICARE (Improving Renal Complications in Adolescents with Type 2 Diabetes through Research), an ongoing prospective cohort study that Dr. Wicklow and her associates launched in 2014 at eight centers in Canada. It aims to examine the biopsychosocial risk factors for albuminuria in youth with T2DM and the mechanisms for renal injury. “Our theoretical framework was that biological exposures that we are aware of, such as glycemic control, hypertension, and lipids, would all be important in the development of albuminuria and renal disease in kids,” said Dr. Wicklow, who is the study’s coprimary investigator along with Allison Dart, MD. “But what we thought was novel was that psychological exposures either as socioeconomic status or as mental health factors would also directly impinge on renal health with respect to chronic inflammation in the body, inflammation in the kidneys, and long-term kidney damage.”
The first phase of ICARE involved a detailed phenotypic assessment of youth, including anthropometrics, biochemistry, 24-hour ambulatory blood pressure monitoring, overnight urine collections for albumin excretion, renal ultrasound, and iohexol-derived glomerular filtration rate (GFR). Phase 2 included an evaluation of psychological factors, including hair-derived cortisol; validated questionnaires for perceived stress, distress, and resiliency; and a detailed evaluation of systemic and urine inflammatory biomarkers. Annual follow-up is carried out to assess temporal associations between clinical risk factors and renal outcomes, including progression of albuminuria.
At the meeting, Dr. Wicklow reported on 187 youth enrolled to date. Of these, 96% were of indigenous ethnicity, 57 had albuminuria and 130 did not, and the mean ages of the groups were 16 years and 15 years, respectively. At baseline, a higher proportion of those in the albuminuria group were female (74% vs. 64% of those in the no albuminuria group, respectively), had a higher mean hemoglobin A1c (11% vs. 9%), and had hypertension (94% vs. 72%). She noted that upon presentation to the clinic, only 23% of participants had HbA1c levels less than 7%, only 26% had ranges between 7% and 9%, and about 40% did not have any hypertension. Of those who did, 27% had nighttime-only hypertension, and only 2% had daytime-only hypertension.
“The other risk factor these kids have for developing ESRD is that the majority were exposed to diabetes in pregnancy,” Dr. Wicklow said. “Murine models of maternal diabetes exposure have demonstrated that offspring have small kidneys, less ureteric bud branching, and a lower number of nephrons. Most of the human clinical cohort studies look at associations between development of diabetes and parental hypertension, maternal smoking, and maternal education. There is likely an impact at birth that sets these kids up for development of type 2 diabetes.”
In addition, results from clinical cohort studies have found that depression, mental stress, and distress are high in youth with T2DM. “Preliminary data suggest that if you have positive mental health, or coping strategies, or someone has worked through this with you and you are resilient, you might benefit in terms of overall glycemic control,” she said. For example, ICARE investigators have found that the higher the score on the Kessler Psychological Distress Scale (K6), the greater the risk of renal inflammation as measured by monocyte chemotactic protein-1 (MCP-1; P = .02). “Mental health seems to be something that can directly impact your health from a biological standpoint, and we might be able to find biomarkers of that risk,” Dr. Wicklow said. “Where does the stress come from? Most of my patients are indigenous, so it’s not surprising that the history in Canada of colonization of residential schools has left a lasting impression on these families and communities in terms of loss of language, loss of culture, and loss of land. There’s a community-based stress and a family-based stress that these children feel.”
Social factors also play a big role. She presented baseline findings from 196 youth with T2DM and 456 with T1DM, including measures such as the Socioeconomic Factor Index-Version 2 (SEFI-2), a way to assess socioeconomic characteristics based on Canadian Census data that reflects nonmedical social determinants of health. “It looks at factors like number of rooms in the house, single-parent households, maternal education attainment, and family income,” Dr. Wicklow explained. “The higher the SEFI-2 score, the lower your socioeconomic status is for the area you live in. Kids with T2DM generally live in areas of lower SES and lower socioeconomic index. They often live far away from health care providers. Many do not attend school and many are not with their biologic families, so we’ve had a lot of issues addressing child and family services, in particular in the phase of a chronic illness where our expectation is one thing and the family’s and community’s expectations of what’s realistic in terms of treatment and goals is another. We also have a lot of adolescent pregnancies.”
To date, about 80% of youth with T1D have seen a health care provider within the first year after transition from the pediatric diabetes clinic, compared with just over 50% of kids with T2D. “We transition youth with T1DM to internists, while our youth with T2DM go to itinerant physicians often back in their communities and/or rural family physicians,” she said. Between baseline and year 2, the rate of hospital admissions remained similar among T1DM at 11.6 and 11.8 admissions per 100 patient-years, respectively, but the number of hospital admissions for T2DM patients jumped from 20.1 to 25.5 admissions per 100 patient-years. “Kids with type 2 are showing up in the hospital a lot more than those with type 1 diabetes, but not for diabetes-related diagnoses,” Dr. Wicklow said. “We’re starting to look through the data now, and most of our kids are showing up with mental health complaints and issues. That’s why they’re getting hospitalized.”
Among ICARE study participants who have completed 3 years of follow-up, about 52% had albuminuria at their baseline visit and 48% sustained albuminuria throughout the study. About 26% progressed from normal levels of albuminuria to microalbuminuria, from microalbuminuria to macroalbuminuria, or from normal levels of albuminuria to macroalbuminuria. In addition, 16% persisted in the category that they were in, and 10% regressed. “The good news is, some of our kids get better over time,” Dr. Wicklow said. “The bad news is that the majority do not.”
Going forward, Dr. Wicklow and her associates work with an ICARE advisory group composed of children and families “who sit with us and talk about what mental health needs might be important, and how we should organize our study in a follow-up of the kids, to try and answer some of the questions that are important,” she said. “Working with the concept of the study’s theoretical framework, they acknowledged that the biological exposures are important, but they were also concerned about food security, finding strength/resilience within the community, and finding coping factors in terms of keeping themselves healthy with their diabetes. For some communities, they are concerned with basic needs. We’re working with them to help them progress, and to figure out how to best study children with type 2 diabetes.”
ICARE has received support from Diabetes Canada, Research Manitoba, the Canadian Institutes of Health Research, the Children’s Hospital Research Institute of Manitoba (specifically the Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) theme), and the University of Manitoba. Dr. Wicklow reported having no financial disclosures.
AT PAS 18
Key clinical point: Mental health may indirectly increase inflammation, which contributes to kidney health.
Major finding: The higher the score on the Kessler Psychological Distress Scale (K6), the greater the risk of renal inflammation as measured by MCP-1 (P = .02).
Study details: Preliminary results from ICARE (Improving Renal Complications in Adolescents with Type 2 Diabetes through Research), an ongoing prospective cohort study.
Disclosures: ICARE has received support from Diabetes Canada, Research Manitoba, the Canadian Institutes of Health Research, the Children’s Hospital Research Institute of Manitoba (specifically the Diabetes Research Envisioned and Accomplished in Manitoba [DREAM] theme), and the University of Manitoba. Dr. Wicklow reported having no financial disclosures.
EC approves new use, formulation of dasatinib
The European Commission (EC) has expanded the marketing authorization for dasatinib (Sprycel).
The drug is now approved to treat patients ages 1 to 18 with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).
The EC has also approved a new formulation of dasatinib—a powder for oral suspension (PFOS) intended for patients who cannot swallow tablets whole or who weigh 10 kg or less.
Dasatinib is also EC-approved to treat adults with:
- Newly diagnosed Ph+ CML-CP
- Chronic, accelerated, or blast phase CML with resistance or intolerance to prior therapy, including imatinib
- Ph+ acute lymphoblastic leukemia and lymphoid blast CML with resistance or intolerance to prior therapy.
The EC’s latest approval of dasatinib is supported by results from a phase 2 trial (NCT00777036), which were published in the Journal of Clinical Oncology in March.
The trial included 29 patients with imatinib-resistant/intolerant CML-CP and 84 patients with newly diagnosed CML-CP.
The previously treated patients received dasatinib tablets. Newly diagnosed patients were treated with dasatinib tablets (n=51) or PFOS (n=33).
Patients who started on PFOS could switch to tablets after receiving PFOS for at least 1 year. Sixty-seven percent of patients on PFOS switched to tablets due to patient preference.
The average daily dose of dasatinib was 58.18 mg/m2 in the previously treated patients and 59.84 mg/m2 in the newly diagnosed patients (for both tablets and PFOS). The median duration of treatment was 49.91 months (range, 1.9 to 90.2) and 42.30 months (range, 0.1 to 75.2), respectively.
Rates of confirmed complete hematologic response (CHR) at any time were 93% in the previously treated patients and 96% in the newly diagnosed patients.
At 12 months, previously treated patients had a major molecular response (MMR) rate of 41% and a complete molecular response (CMR) rate of 7%. In newly diagnosed patients, MMR was 52%, and CMR was 8%.
At 24 months, previously treated patients had an MMR rate of 55% and a CMR rate of 17%. In the newly diagnosed patients, MMR was 70%, and CMR was 21%.
The rate of major cytogenetic response (MCyR) at any time was 89.7% in all previously treated patients and 90% when the researchers excluded patients with MCyR or unknown cytogenetic status at baseline.
The rate of complete cytogenetic response (CCyR) at any time was 94% in all newly diagnosed patients and 93.9% when the researchers excluded patients with CCyR or unknown cytogenetic status at baseline.
The median progression-free survival and overall survival had not been reached at last follow-up.
The estimated 48-month progression-free survival was 78% in the previously treated patients and 93% in the newly diagnosed patients. The estimated 48-month overall survival was 96% and 100%, respectively.
Dasatinib-related adverse events (AEs) occurring in at least 10% of the previously treated patients included nausea/vomiting (31%), myalgia/arthralgia (17%), fatigue (14%), rash (14%), diarrhea (14%), hemorrhage (10%), bone growth and development events (10%), and shortness of breath (10%).
Dasatinib-related AEs occurring in at least 10% of the newly diagnosed patients included nausea/vomiting (20%), myalgia/arthralgia (10%), fatigue (11%), rash (19%), diarrhea (18%), and hemorrhage (10%).
The European Commission (EC) has expanded the marketing authorization for dasatinib (Sprycel).
The drug is now approved to treat patients ages 1 to 18 with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).
The EC has also approved a new formulation of dasatinib—a powder for oral suspension (PFOS) intended for patients who cannot swallow tablets whole or who weigh 10 kg or less.
Dasatinib is also EC-approved to treat adults with:
- Newly diagnosed Ph+ CML-CP
- Chronic, accelerated, or blast phase CML with resistance or intolerance to prior therapy, including imatinib
- Ph+ acute lymphoblastic leukemia and lymphoid blast CML with resistance or intolerance to prior therapy.
The EC’s latest approval of dasatinib is supported by results from a phase 2 trial (NCT00777036), which were published in the Journal of Clinical Oncology in March.
The trial included 29 patients with imatinib-resistant/intolerant CML-CP and 84 patients with newly diagnosed CML-CP.
The previously treated patients received dasatinib tablets. Newly diagnosed patients were treated with dasatinib tablets (n=51) or PFOS (n=33).
Patients who started on PFOS could switch to tablets after receiving PFOS for at least 1 year. Sixty-seven percent of patients on PFOS switched to tablets due to patient preference.
The average daily dose of dasatinib was 58.18 mg/m2 in the previously treated patients and 59.84 mg/m2 in the newly diagnosed patients (for both tablets and PFOS). The median duration of treatment was 49.91 months (range, 1.9 to 90.2) and 42.30 months (range, 0.1 to 75.2), respectively.
Rates of confirmed complete hematologic response (CHR) at any time were 93% in the previously treated patients and 96% in the newly diagnosed patients.
At 12 months, previously treated patients had a major molecular response (MMR) rate of 41% and a complete molecular response (CMR) rate of 7%. In newly diagnosed patients, MMR was 52%, and CMR was 8%.
At 24 months, previously treated patients had an MMR rate of 55% and a CMR rate of 17%. In the newly diagnosed patients, MMR was 70%, and CMR was 21%.
The rate of major cytogenetic response (MCyR) at any time was 89.7% in all previously treated patients and 90% when the researchers excluded patients with MCyR or unknown cytogenetic status at baseline.
The rate of complete cytogenetic response (CCyR) at any time was 94% in all newly diagnosed patients and 93.9% when the researchers excluded patients with CCyR or unknown cytogenetic status at baseline.
The median progression-free survival and overall survival had not been reached at last follow-up.
The estimated 48-month progression-free survival was 78% in the previously treated patients and 93% in the newly diagnosed patients. The estimated 48-month overall survival was 96% and 100%, respectively.
Dasatinib-related adverse events (AEs) occurring in at least 10% of the previously treated patients included nausea/vomiting (31%), myalgia/arthralgia (17%), fatigue (14%), rash (14%), diarrhea (14%), hemorrhage (10%), bone growth and development events (10%), and shortness of breath (10%).
Dasatinib-related AEs occurring in at least 10% of the newly diagnosed patients included nausea/vomiting (20%), myalgia/arthralgia (10%), fatigue (11%), rash (19%), diarrhea (18%), and hemorrhage (10%).
The European Commission (EC) has expanded the marketing authorization for dasatinib (Sprycel).
The drug is now approved to treat patients ages 1 to 18 with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).
The EC has also approved a new formulation of dasatinib—a powder for oral suspension (PFOS) intended for patients who cannot swallow tablets whole or who weigh 10 kg or less.
Dasatinib is also EC-approved to treat adults with:
- Newly diagnosed Ph+ CML-CP
- Chronic, accelerated, or blast phase CML with resistance or intolerance to prior therapy, including imatinib
- Ph+ acute lymphoblastic leukemia and lymphoid blast CML with resistance or intolerance to prior therapy.
The EC’s latest approval of dasatinib is supported by results from a phase 2 trial (NCT00777036), which were published in the Journal of Clinical Oncology in March.
The trial included 29 patients with imatinib-resistant/intolerant CML-CP and 84 patients with newly diagnosed CML-CP.
The previously treated patients received dasatinib tablets. Newly diagnosed patients were treated with dasatinib tablets (n=51) or PFOS (n=33).
Patients who started on PFOS could switch to tablets after receiving PFOS for at least 1 year. Sixty-seven percent of patients on PFOS switched to tablets due to patient preference.
The average daily dose of dasatinib was 58.18 mg/m2 in the previously treated patients and 59.84 mg/m2 in the newly diagnosed patients (for both tablets and PFOS). The median duration of treatment was 49.91 months (range, 1.9 to 90.2) and 42.30 months (range, 0.1 to 75.2), respectively.
Rates of confirmed complete hematologic response (CHR) at any time were 93% in the previously treated patients and 96% in the newly diagnosed patients.
At 12 months, previously treated patients had a major molecular response (MMR) rate of 41% and a complete molecular response (CMR) rate of 7%. In newly diagnosed patients, MMR was 52%, and CMR was 8%.
At 24 months, previously treated patients had an MMR rate of 55% and a CMR rate of 17%. In the newly diagnosed patients, MMR was 70%, and CMR was 21%.
The rate of major cytogenetic response (MCyR) at any time was 89.7% in all previously treated patients and 90% when the researchers excluded patients with MCyR or unknown cytogenetic status at baseline.
The rate of complete cytogenetic response (CCyR) at any time was 94% in all newly diagnosed patients and 93.9% when the researchers excluded patients with CCyR or unknown cytogenetic status at baseline.
The median progression-free survival and overall survival had not been reached at last follow-up.
The estimated 48-month progression-free survival was 78% in the previously treated patients and 93% in the newly diagnosed patients. The estimated 48-month overall survival was 96% and 100%, respectively.
Dasatinib-related adverse events (AEs) occurring in at least 10% of the previously treated patients included nausea/vomiting (31%), myalgia/arthralgia (17%), fatigue (14%), rash (14%), diarrhea (14%), hemorrhage (10%), bone growth and development events (10%), and shortness of breath (10%).
Dasatinib-related AEs occurring in at least 10% of the newly diagnosed patients included nausea/vomiting (20%), myalgia/arthralgia (10%), fatigue (11%), rash (19%), diarrhea (18%), and hemorrhage (10%).