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BMI screening trigger for type 2 diabetes is unreliable for at-risk black, Hispanic adults
SAN FRANCISCO – according to findings presented at the annual scientific sessions of the American Diabetes Association.
The conclusions come from a review of 5,656 participants aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective cohort study. The participants had no signs of cardiovascular disease at enrollment.
The goal of the study reported at the meeting was to see if current ADA screening guidelines are appropriate across racial groups in an increasingly diverse United States. The guidelines recommend body mass index (BMI) as a trigger for screening for type 2 diabetes. The current advice is to screen any adult who has a BMI at or above 25 kg/m2 (23 kg/m2 for Asian Americans) and at least one risk factor for type 2 diabetes, such as hypertension, dyslipidemia, or physical inactivity.
Being black, Asian American, Hispanic, Pacific Islander, or American Indian is itself a risk factor, so “someone from a minority group just needs to meet the BMI criteria,” said lead investigator Luis Rodriguez, a PhD candidate in epidemiology at the University of California, San Francisco.
He and his colleagues focused on 2,383 white, 653 Chinese American, 1,459 black, and 1,161 Hispanic participants in MESA who did not have type 2 diabetes at baseline. Participants were in their early 60s at baseline, on average, and just more than half of them were women. They had five medical exams between 2000 and 2012. The investigators calculated the BMI at which each group hit a 10% risk of developing diabetes within the next 10 years.
In general, the lines crossed at a BMI of about 23 kg/m2 for Chinese Americans; 25 kg/m2 for black and Hispanic participants; and 27 kg/m2 for white participants, which is consistent with ADA advice. The guideline cut points are “appropriate for population-based screening where you may not know if the person in front of you has any diabetes risk factors,” Mr. Rodriguez said.
With known risk factors, however, BMI didn’t hold up. Black participants with one or more risk factor hit the 10% mark at a BMI of 24.7 kg/m2, Hispanics at 23.8 kg/m2, and Chinese Americans at 21.7 kg/m2, all of which are below the recommended cut-points.
“Almost 80%-90% of participants” in minority groups “who had one or more risk factors were above the 10% threshold, so if they have at least one factor, they should pretty much be screened for diabetes, regardless of BMI,” he said.
The 25-kg/m2 threshold worked for white participants; the investigators found that with one or more risk factors, white participants crossed the 10% line at a BMI of 26.2 kg/m2. In addition, white participants with no diabetes risk factors crossed the 10% mark at around a BMI of 30 kg/m2, which the investigators suggested as an appropriate screening trigger.
Participants were in their early 60s at baseline, on average, and just more than half of them were women. In all, 696 cases of type 2 diabetes were diagnosed over a median follow-up of about 9 years, which translated to an incidence rate of 11 cases per 1,000 person-years in white participants, 16 cases for Chinese Americans, 21 for black participants, and 22 for Hispanic participants. Well over half of the participants were overweight or obese at baseline, including about 80% of black and Hispanic participants.
The sample size reported in the abstract was smaller than that in the final presentation because the investigators did not adjust for diet in the final presentation, Mr. Rodriguez explained. Because some study participants did not report diet, by excluding diet from the model adjustment, the number of participants increased, as reflected in this text. Adjusting for diet did not alter the findings.
The National Heart, Lung, and Blood Institute sponsors MESA. Mr. Rodriguez was supported by a grant from the National Institutes of Health/National Institute of Diabetes and Kidney Disease. The other investigators reported having no disclosures.
SOURCE: Rodriguez L et al. ADA 2019, Abstract 115-OR.
SAN FRANCISCO – according to findings presented at the annual scientific sessions of the American Diabetes Association.
The conclusions come from a review of 5,656 participants aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective cohort study. The participants had no signs of cardiovascular disease at enrollment.
The goal of the study reported at the meeting was to see if current ADA screening guidelines are appropriate across racial groups in an increasingly diverse United States. The guidelines recommend body mass index (BMI) as a trigger for screening for type 2 diabetes. The current advice is to screen any adult who has a BMI at or above 25 kg/m2 (23 kg/m2 for Asian Americans) and at least one risk factor for type 2 diabetes, such as hypertension, dyslipidemia, or physical inactivity.
Being black, Asian American, Hispanic, Pacific Islander, or American Indian is itself a risk factor, so “someone from a minority group just needs to meet the BMI criteria,” said lead investigator Luis Rodriguez, a PhD candidate in epidemiology at the University of California, San Francisco.
He and his colleagues focused on 2,383 white, 653 Chinese American, 1,459 black, and 1,161 Hispanic participants in MESA who did not have type 2 diabetes at baseline. Participants were in their early 60s at baseline, on average, and just more than half of them were women. They had five medical exams between 2000 and 2012. The investigators calculated the BMI at which each group hit a 10% risk of developing diabetes within the next 10 years.
In general, the lines crossed at a BMI of about 23 kg/m2 for Chinese Americans; 25 kg/m2 for black and Hispanic participants; and 27 kg/m2 for white participants, which is consistent with ADA advice. The guideline cut points are “appropriate for population-based screening where you may not know if the person in front of you has any diabetes risk factors,” Mr. Rodriguez said.
With known risk factors, however, BMI didn’t hold up. Black participants with one or more risk factor hit the 10% mark at a BMI of 24.7 kg/m2, Hispanics at 23.8 kg/m2, and Chinese Americans at 21.7 kg/m2, all of which are below the recommended cut-points.
“Almost 80%-90% of participants” in minority groups “who had one or more risk factors were above the 10% threshold, so if they have at least one factor, they should pretty much be screened for diabetes, regardless of BMI,” he said.
The 25-kg/m2 threshold worked for white participants; the investigators found that with one or more risk factors, white participants crossed the 10% line at a BMI of 26.2 kg/m2. In addition, white participants with no diabetes risk factors crossed the 10% mark at around a BMI of 30 kg/m2, which the investigators suggested as an appropriate screening trigger.
Participants were in their early 60s at baseline, on average, and just more than half of them were women. In all, 696 cases of type 2 diabetes were diagnosed over a median follow-up of about 9 years, which translated to an incidence rate of 11 cases per 1,000 person-years in white participants, 16 cases for Chinese Americans, 21 for black participants, and 22 for Hispanic participants. Well over half of the participants were overweight or obese at baseline, including about 80% of black and Hispanic participants.
The sample size reported in the abstract was smaller than that in the final presentation because the investigators did not adjust for diet in the final presentation, Mr. Rodriguez explained. Because some study participants did not report diet, by excluding diet from the model adjustment, the number of participants increased, as reflected in this text. Adjusting for diet did not alter the findings.
The National Heart, Lung, and Blood Institute sponsors MESA. Mr. Rodriguez was supported by a grant from the National Institutes of Health/National Institute of Diabetes and Kidney Disease. The other investigators reported having no disclosures.
SOURCE: Rodriguez L et al. ADA 2019, Abstract 115-OR.
SAN FRANCISCO – according to findings presented at the annual scientific sessions of the American Diabetes Association.
The conclusions come from a review of 5,656 participants aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective cohort study. The participants had no signs of cardiovascular disease at enrollment.
The goal of the study reported at the meeting was to see if current ADA screening guidelines are appropriate across racial groups in an increasingly diverse United States. The guidelines recommend body mass index (BMI) as a trigger for screening for type 2 diabetes. The current advice is to screen any adult who has a BMI at or above 25 kg/m2 (23 kg/m2 for Asian Americans) and at least one risk factor for type 2 diabetes, such as hypertension, dyslipidemia, or physical inactivity.
Being black, Asian American, Hispanic, Pacific Islander, or American Indian is itself a risk factor, so “someone from a minority group just needs to meet the BMI criteria,” said lead investigator Luis Rodriguez, a PhD candidate in epidemiology at the University of California, San Francisco.
He and his colleagues focused on 2,383 white, 653 Chinese American, 1,459 black, and 1,161 Hispanic participants in MESA who did not have type 2 diabetes at baseline. Participants were in their early 60s at baseline, on average, and just more than half of them were women. They had five medical exams between 2000 and 2012. The investigators calculated the BMI at which each group hit a 10% risk of developing diabetes within the next 10 years.
In general, the lines crossed at a BMI of about 23 kg/m2 for Chinese Americans; 25 kg/m2 for black and Hispanic participants; and 27 kg/m2 for white participants, which is consistent with ADA advice. The guideline cut points are “appropriate for population-based screening where you may not know if the person in front of you has any diabetes risk factors,” Mr. Rodriguez said.
With known risk factors, however, BMI didn’t hold up. Black participants with one or more risk factor hit the 10% mark at a BMI of 24.7 kg/m2, Hispanics at 23.8 kg/m2, and Chinese Americans at 21.7 kg/m2, all of which are below the recommended cut-points.
“Almost 80%-90% of participants” in minority groups “who had one or more risk factors were above the 10% threshold, so if they have at least one factor, they should pretty much be screened for diabetes, regardless of BMI,” he said.
The 25-kg/m2 threshold worked for white participants; the investigators found that with one or more risk factors, white participants crossed the 10% line at a BMI of 26.2 kg/m2. In addition, white participants with no diabetes risk factors crossed the 10% mark at around a BMI of 30 kg/m2, which the investigators suggested as an appropriate screening trigger.
Participants were in their early 60s at baseline, on average, and just more than half of them were women. In all, 696 cases of type 2 diabetes were diagnosed over a median follow-up of about 9 years, which translated to an incidence rate of 11 cases per 1,000 person-years in white participants, 16 cases for Chinese Americans, 21 for black participants, and 22 for Hispanic participants. Well over half of the participants were overweight or obese at baseline, including about 80% of black and Hispanic participants.
The sample size reported in the abstract was smaller than that in the final presentation because the investigators did not adjust for diet in the final presentation, Mr. Rodriguez explained. Because some study participants did not report diet, by excluding diet from the model adjustment, the number of participants increased, as reflected in this text. Adjusting for diet did not alter the findings.
The National Heart, Lung, and Blood Institute sponsors MESA. Mr. Rodriguez was supported by a grant from the National Institutes of Health/National Institute of Diabetes and Kidney Disease. The other investigators reported having no disclosures.
SOURCE: Rodriguez L et al. ADA 2019, Abstract 115-OR.
REPORTING FROM ADA 2019
Key clinical point:
Major finding: Black participants with one or more risk factors had a 10% or greater risk of type 2 diabetes at a BMI of 24.7 kg/m2; Hispanic participants had the same risk at 23.8 kg/m2; and Chinese Americans at 21.7 kg/mg2, all of which are below the BMI cut points recommended by the ADA.
Study details: Review of 5,656 participants in the Multi-Ethnic Study of Atherosclerosis .
Disclosures: The National Heart, Lung, and Blood Institute sponsors MESA. Mr. Rodriguez was supported by grant from the National Institutes of Health/National Institute of Diabetes and Kidney Disease. The other investigators reported having no disclosures.
Source: Rodriguez L et al. ADA 2019, Abstract 115-OR.
Low-fat dairy associated with decreased risk of type 2 diabetes
SAN FRANCISCO – in a review of almost 200,000 participants presented at the annual scientific sessions at the American Diabetes Association.
Increasing yogurt consumption was also independently associated with a moderately lower risk of type 2 diabetes, and increasing cheese consumption with a moderately higher risk.
It might have been that yogurt and low-fat milk were simply indicators of healthier living and that cheese consumption – in the study, most commonly on pizza or as processed slices on cheeseburgers – indicated a less healthy way of life, but “we tried our best to control for confounders,” said study lead Jean-Philippe Drouin-Chartier, PhD, of the Harvard School of Public Health, Boston.
And it is possible, he said, that lactic acid bacteria in yogurt could have some effect on the gut microbiome that protects against type 2 disease.
Total dairy consumption has not changed much over the past few decades, but people are drinking less milk and eating more cheese and yogurt. Dr. Drouin-Chartier and colleagues wondered how that affected the risk of type 2 diabetes.
The investigators correlated changes in dairy consumption during 4-year intervals with the incidence of type 2 diabetes in subsequent 4-year intervals using three large, prospective cohort studies that all started about 30 years ago: the Health Professionals Follow-Up Study, Nurses’ Health Study I, and Nurses’ Health Study II.
There were almost 200,000 participants in the pooled analysis, with 2.9 million person-years of follow-up and 12,007 new cases of type 2 diabetes. Participants completed food-frequency questionnaires every 4 years. About 82% of the participants were women. At baseline, they reported consuming about one to four servings of dairy a day.
After adjustment for race, body mass index, calorie intake, family history, physical activity, and other factors associated with type 2 diabetes, the investigators found that increasing yogurt intake by one 4-ounce serving a day while decreasing cheese intake by one 1-ounce serving a day was associated with a 16% (95% confidence interval, 10%-22%) reduction in subsequent risk of type 2 disease. There was an 11% (95% CI, 7%-15%) reduction in risk when a cheese serving was subbed out for a daily 8-ounce serving of reduced-fat milk.
An extra 2 ounces of yogurt a day was associated with a 13% (95% CI, 6%-19%) lower risk of type 2 diabetes, compared with stable consumption, while an extra half ounce of cheese was associated with an 8% (95% CI, 2%-16%) increase in risk.
Overall, substitution of low-fat products (such as 0%-2% milk and low-fat cheese, yogurt, or sherbet) for high-fat products (such as whole milk, ice cream, and high-fat cheese) was associated with a 4% decrease in risk (hazard ratio, 0.96; 95% CI, 0.93-0.99).
However, substitution of reduced-fat milk for whole milk or low-fat cheese for high-fat cheese did not influence the risk, possibly because there is actually not much difference in fat content, Dr. Drouin-Chartier said.
The National Institutes of Health funded the study. Dr. Drouin-Chartier has served as a speaker and consultant for Dairy Farmers of Canada, one other author has advised the group, another has advised the U.S. Department of Agriculture, and the remaining authors had no disclosures.
SOURCE: Drouin-Chartier J et al. ADA 2019, Abstract 159-OR.
SAN FRANCISCO – in a review of almost 200,000 participants presented at the annual scientific sessions at the American Diabetes Association.
Increasing yogurt consumption was also independently associated with a moderately lower risk of type 2 diabetes, and increasing cheese consumption with a moderately higher risk.
It might have been that yogurt and low-fat milk were simply indicators of healthier living and that cheese consumption – in the study, most commonly on pizza or as processed slices on cheeseburgers – indicated a less healthy way of life, but “we tried our best to control for confounders,” said study lead Jean-Philippe Drouin-Chartier, PhD, of the Harvard School of Public Health, Boston.
And it is possible, he said, that lactic acid bacteria in yogurt could have some effect on the gut microbiome that protects against type 2 disease.
Total dairy consumption has not changed much over the past few decades, but people are drinking less milk and eating more cheese and yogurt. Dr. Drouin-Chartier and colleagues wondered how that affected the risk of type 2 diabetes.
The investigators correlated changes in dairy consumption during 4-year intervals with the incidence of type 2 diabetes in subsequent 4-year intervals using three large, prospective cohort studies that all started about 30 years ago: the Health Professionals Follow-Up Study, Nurses’ Health Study I, and Nurses’ Health Study II.
There were almost 200,000 participants in the pooled analysis, with 2.9 million person-years of follow-up and 12,007 new cases of type 2 diabetes. Participants completed food-frequency questionnaires every 4 years. About 82% of the participants were women. At baseline, they reported consuming about one to four servings of dairy a day.
After adjustment for race, body mass index, calorie intake, family history, physical activity, and other factors associated with type 2 diabetes, the investigators found that increasing yogurt intake by one 4-ounce serving a day while decreasing cheese intake by one 1-ounce serving a day was associated with a 16% (95% confidence interval, 10%-22%) reduction in subsequent risk of type 2 disease. There was an 11% (95% CI, 7%-15%) reduction in risk when a cheese serving was subbed out for a daily 8-ounce serving of reduced-fat milk.
An extra 2 ounces of yogurt a day was associated with a 13% (95% CI, 6%-19%) lower risk of type 2 diabetes, compared with stable consumption, while an extra half ounce of cheese was associated with an 8% (95% CI, 2%-16%) increase in risk.
Overall, substitution of low-fat products (such as 0%-2% milk and low-fat cheese, yogurt, or sherbet) for high-fat products (such as whole milk, ice cream, and high-fat cheese) was associated with a 4% decrease in risk (hazard ratio, 0.96; 95% CI, 0.93-0.99).
However, substitution of reduced-fat milk for whole milk or low-fat cheese for high-fat cheese did not influence the risk, possibly because there is actually not much difference in fat content, Dr. Drouin-Chartier said.
The National Institutes of Health funded the study. Dr. Drouin-Chartier has served as a speaker and consultant for Dairy Farmers of Canada, one other author has advised the group, another has advised the U.S. Department of Agriculture, and the remaining authors had no disclosures.
SOURCE: Drouin-Chartier J et al. ADA 2019, Abstract 159-OR.
SAN FRANCISCO – in a review of almost 200,000 participants presented at the annual scientific sessions at the American Diabetes Association.
Increasing yogurt consumption was also independently associated with a moderately lower risk of type 2 diabetes, and increasing cheese consumption with a moderately higher risk.
It might have been that yogurt and low-fat milk were simply indicators of healthier living and that cheese consumption – in the study, most commonly on pizza or as processed slices on cheeseburgers – indicated a less healthy way of life, but “we tried our best to control for confounders,” said study lead Jean-Philippe Drouin-Chartier, PhD, of the Harvard School of Public Health, Boston.
And it is possible, he said, that lactic acid bacteria in yogurt could have some effect on the gut microbiome that protects against type 2 disease.
Total dairy consumption has not changed much over the past few decades, but people are drinking less milk and eating more cheese and yogurt. Dr. Drouin-Chartier and colleagues wondered how that affected the risk of type 2 diabetes.
The investigators correlated changes in dairy consumption during 4-year intervals with the incidence of type 2 diabetes in subsequent 4-year intervals using three large, prospective cohort studies that all started about 30 years ago: the Health Professionals Follow-Up Study, Nurses’ Health Study I, and Nurses’ Health Study II.
There were almost 200,000 participants in the pooled analysis, with 2.9 million person-years of follow-up and 12,007 new cases of type 2 diabetes. Participants completed food-frequency questionnaires every 4 years. About 82% of the participants were women. At baseline, they reported consuming about one to four servings of dairy a day.
After adjustment for race, body mass index, calorie intake, family history, physical activity, and other factors associated with type 2 diabetes, the investigators found that increasing yogurt intake by one 4-ounce serving a day while decreasing cheese intake by one 1-ounce serving a day was associated with a 16% (95% confidence interval, 10%-22%) reduction in subsequent risk of type 2 disease. There was an 11% (95% CI, 7%-15%) reduction in risk when a cheese serving was subbed out for a daily 8-ounce serving of reduced-fat milk.
An extra 2 ounces of yogurt a day was associated with a 13% (95% CI, 6%-19%) lower risk of type 2 diabetes, compared with stable consumption, while an extra half ounce of cheese was associated with an 8% (95% CI, 2%-16%) increase in risk.
Overall, substitution of low-fat products (such as 0%-2% milk and low-fat cheese, yogurt, or sherbet) for high-fat products (such as whole milk, ice cream, and high-fat cheese) was associated with a 4% decrease in risk (hazard ratio, 0.96; 95% CI, 0.93-0.99).
However, substitution of reduced-fat milk for whole milk or low-fat cheese for high-fat cheese did not influence the risk, possibly because there is actually not much difference in fat content, Dr. Drouin-Chartier said.
The National Institutes of Health funded the study. Dr. Drouin-Chartier has served as a speaker and consultant for Dairy Farmers of Canada, one other author has advised the group, another has advised the U.S. Department of Agriculture, and the remaining authors had no disclosures.
SOURCE: Drouin-Chartier J et al. ADA 2019, Abstract 159-OR.
REPORTING FROM ADA 2019
Using Obamacare authority, Trump aims to shift dialysis care to patients’ homes
President Trump on July 10 announced a bold plan to improve care to patients with kidney disease, which he claimed would save thousands of lives each year and billions of dollars for taxpayers.
“It could be higher if it works the way we anticipate,” Mr. Trump boasted in a 25-minute speech to dozens of kidney patients, their families, and kidney care providers in Washington.
Ten Americans die each day because of the shortage of organs, Mr. Trump said.
Kidney disease is the ninth-leading cause of death in the United States and accounts for 20% of annual Medicare spending, or about $110 billion, administration officials said.
Mr. Trump’s strategy centers on changing how Medicare pays doctors and dialysis centers to boost their incentives to help patients get dialysis at home and keep them healthy enough to be eligible for transplantation. This would be a far cry from the current system, which focuses on in-patient dialysis center treatment.
Mark E. Rosenberg, MD, president of the American Society of Nephrology, said he was pleased that some of the new payment models offered by the Centers for Medicare & Medicaid Services have only “upside” potential for doctors. He said doctors now get paid more to see their patients at the dialysis center than at home. As a result, there is little incentive to promote home dialysis options.
“I have been a kidney doctor for 35 years, and this is the most game-changing thing ever to happen,” he said.
The authority to make such major changes without congressional approval comes from the Centers for Medicare and Medicaid Innovation (CMMI), which was created by the 2010 Affordable Care Act.
On Tuesday, the Trump administration was in a federal appeals court in New Orleans arguing the entire health law should be declared unconstitutional.
“If the law is invalidated, the Innovation Center, and all its authorities, would be eliminated,” said Nicholas Bagley, a University of Michigan law professor.
In touting the new effort, Health and Human Services Secretary Alex M. Azar II and CMMI Director Adam Boehler spoke about how kidney disease has affected their families. Mr. Azar noted his father was on dialysis for several years before receiving a kidney transplant. Mr. Boehler said an aunt died while on dialysis.
Since 1973, all Americans with end-stage kidney disease have been entitled to coverage through Medicare.
The administration said it would expand the number of kidneys available for transplant by increasing public awareness about the need for living donors and help those who donate a kidney. Currently, their medical costs are covered, but the president’s plan would provide financial assistance to cover day care and time missed from work. Mr. Trump said the initiative would also hold organ procurement organizations more accountable so that fewer usable organs are discarded.
Trump said his plan would help 17,000 additional Americans get a kidney transplant each year by 2030. The policy would also help 11,000 more Americans get hearts, lungs, and livers annually.
Kidney transplants cost less than having patients spend years on dialysis, according to government figures. Dialysis treatment runs on average about $89,000 a year, while a kidney transplant surgery averages about $32,000 and postsurgery care runs about $25,000 per year. Mr. Trump estimated his plan would save families and taxpayers $4.2 billion a year. “This is a dramatic and long overdue reform,” he said.
In the United States, only about 12% of patients get dialysis at home, far lower than in other countries, Mr. Trump said. The plan calls for increasing that share to 80% by 2025.
Nichole Jefferson, 47 years, of Dallas, who is awaiting a second transplant to replace a transplanted kidney that is failing, said getting the treatment at home is much less taxing. She had home dialysis for 4 years before her initial transplant in 2008.
“It’s great to be at home where I was more comfortable and more relaxed and the care was in my hands,” she said in an interview at the Trump event. By getting dialysis at night while she slept, she was able to work during the day and take part in family events.
She had to go to a center for the dialysis when the home dialysis stopped working. “I was depressed to be in the center tied to a chair for 4 hours next to people I did not know,” she said. Patients often have dialysis several days a week.
Other patient advocates applauded Mr. Trump’s plan.
“The administration’s commitment to charting a new course for kidney health will help revolutionize transplantation and dialysis and advance new innovations, therapies and treatments, which patients everywhere have been waiting on for far too long,” said Kevin Longino, CEO of the National Kidney Foundation and a kidney transplant patient.
DaVita, the Denver-based company that is the largest provider of home dialysis in the country, offered a more muted response, saying it looked forward to working with the administration. The company’s stock, which fell in recent days ahead of the announcement, rose about 5% Wednesday.
Administration officials said many aspects of their plan would begin next year. Health providers in half the country will be required to participate in one of the new payment models in which they will face some financial risk for caring for patients. Doctors and health systems will have options to take on more financial risk, which means they could make more money or lose more money based on the health of their kidney patients.
Patients, however, will continue to be able to choose their doctors and dialysis providers.
Joe Grogan, head of the White House Domestic Policy Council, said the kidney disease issue “fits in the wheelhouse of items the president likes to confront. ... The current quality of outcomes are pathetic in this area.”
About half of patients on dialysis die within 5 years, Mr. Azar said.
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
President Trump on July 10 announced a bold plan to improve care to patients with kidney disease, which he claimed would save thousands of lives each year and billions of dollars for taxpayers.
“It could be higher if it works the way we anticipate,” Mr. Trump boasted in a 25-minute speech to dozens of kidney patients, their families, and kidney care providers in Washington.
Ten Americans die each day because of the shortage of organs, Mr. Trump said.
Kidney disease is the ninth-leading cause of death in the United States and accounts for 20% of annual Medicare spending, or about $110 billion, administration officials said.
Mr. Trump’s strategy centers on changing how Medicare pays doctors and dialysis centers to boost their incentives to help patients get dialysis at home and keep them healthy enough to be eligible for transplantation. This would be a far cry from the current system, which focuses on in-patient dialysis center treatment.
Mark E. Rosenberg, MD, president of the American Society of Nephrology, said he was pleased that some of the new payment models offered by the Centers for Medicare & Medicaid Services have only “upside” potential for doctors. He said doctors now get paid more to see their patients at the dialysis center than at home. As a result, there is little incentive to promote home dialysis options.
“I have been a kidney doctor for 35 years, and this is the most game-changing thing ever to happen,” he said.
The authority to make such major changes without congressional approval comes from the Centers for Medicare and Medicaid Innovation (CMMI), which was created by the 2010 Affordable Care Act.
On Tuesday, the Trump administration was in a federal appeals court in New Orleans arguing the entire health law should be declared unconstitutional.
“If the law is invalidated, the Innovation Center, and all its authorities, would be eliminated,” said Nicholas Bagley, a University of Michigan law professor.
In touting the new effort, Health and Human Services Secretary Alex M. Azar II and CMMI Director Adam Boehler spoke about how kidney disease has affected their families. Mr. Azar noted his father was on dialysis for several years before receiving a kidney transplant. Mr. Boehler said an aunt died while on dialysis.
Since 1973, all Americans with end-stage kidney disease have been entitled to coverage through Medicare.
The administration said it would expand the number of kidneys available for transplant by increasing public awareness about the need for living donors and help those who donate a kidney. Currently, their medical costs are covered, but the president’s plan would provide financial assistance to cover day care and time missed from work. Mr. Trump said the initiative would also hold organ procurement organizations more accountable so that fewer usable organs are discarded.
Trump said his plan would help 17,000 additional Americans get a kidney transplant each year by 2030. The policy would also help 11,000 more Americans get hearts, lungs, and livers annually.
Kidney transplants cost less than having patients spend years on dialysis, according to government figures. Dialysis treatment runs on average about $89,000 a year, while a kidney transplant surgery averages about $32,000 and postsurgery care runs about $25,000 per year. Mr. Trump estimated his plan would save families and taxpayers $4.2 billion a year. “This is a dramatic and long overdue reform,” he said.
In the United States, only about 12% of patients get dialysis at home, far lower than in other countries, Mr. Trump said. The plan calls for increasing that share to 80% by 2025.
Nichole Jefferson, 47 years, of Dallas, who is awaiting a second transplant to replace a transplanted kidney that is failing, said getting the treatment at home is much less taxing. She had home dialysis for 4 years before her initial transplant in 2008.
“It’s great to be at home where I was more comfortable and more relaxed and the care was in my hands,” she said in an interview at the Trump event. By getting dialysis at night while she slept, she was able to work during the day and take part in family events.
She had to go to a center for the dialysis when the home dialysis stopped working. “I was depressed to be in the center tied to a chair for 4 hours next to people I did not know,” she said. Patients often have dialysis several days a week.
Other patient advocates applauded Mr. Trump’s plan.
“The administration’s commitment to charting a new course for kidney health will help revolutionize transplantation and dialysis and advance new innovations, therapies and treatments, which patients everywhere have been waiting on for far too long,” said Kevin Longino, CEO of the National Kidney Foundation and a kidney transplant patient.
DaVita, the Denver-based company that is the largest provider of home dialysis in the country, offered a more muted response, saying it looked forward to working with the administration. The company’s stock, which fell in recent days ahead of the announcement, rose about 5% Wednesday.
Administration officials said many aspects of their plan would begin next year. Health providers in half the country will be required to participate in one of the new payment models in which they will face some financial risk for caring for patients. Doctors and health systems will have options to take on more financial risk, which means they could make more money or lose more money based on the health of their kidney patients.
Patients, however, will continue to be able to choose their doctors and dialysis providers.
Joe Grogan, head of the White House Domestic Policy Council, said the kidney disease issue “fits in the wheelhouse of items the president likes to confront. ... The current quality of outcomes are pathetic in this area.”
About half of patients on dialysis die within 5 years, Mr. Azar said.
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
President Trump on July 10 announced a bold plan to improve care to patients with kidney disease, which he claimed would save thousands of lives each year and billions of dollars for taxpayers.
“It could be higher if it works the way we anticipate,” Mr. Trump boasted in a 25-minute speech to dozens of kidney patients, their families, and kidney care providers in Washington.
Ten Americans die each day because of the shortage of organs, Mr. Trump said.
Kidney disease is the ninth-leading cause of death in the United States and accounts for 20% of annual Medicare spending, or about $110 billion, administration officials said.
Mr. Trump’s strategy centers on changing how Medicare pays doctors and dialysis centers to boost their incentives to help patients get dialysis at home and keep them healthy enough to be eligible for transplantation. This would be a far cry from the current system, which focuses on in-patient dialysis center treatment.
Mark E. Rosenberg, MD, president of the American Society of Nephrology, said he was pleased that some of the new payment models offered by the Centers for Medicare & Medicaid Services have only “upside” potential for doctors. He said doctors now get paid more to see their patients at the dialysis center than at home. As a result, there is little incentive to promote home dialysis options.
“I have been a kidney doctor for 35 years, and this is the most game-changing thing ever to happen,” he said.
The authority to make such major changes without congressional approval comes from the Centers for Medicare and Medicaid Innovation (CMMI), which was created by the 2010 Affordable Care Act.
On Tuesday, the Trump administration was in a federal appeals court in New Orleans arguing the entire health law should be declared unconstitutional.
“If the law is invalidated, the Innovation Center, and all its authorities, would be eliminated,” said Nicholas Bagley, a University of Michigan law professor.
In touting the new effort, Health and Human Services Secretary Alex M. Azar II and CMMI Director Adam Boehler spoke about how kidney disease has affected their families. Mr. Azar noted his father was on dialysis for several years before receiving a kidney transplant. Mr. Boehler said an aunt died while on dialysis.
Since 1973, all Americans with end-stage kidney disease have been entitled to coverage through Medicare.
The administration said it would expand the number of kidneys available for transplant by increasing public awareness about the need for living donors and help those who donate a kidney. Currently, their medical costs are covered, but the president’s plan would provide financial assistance to cover day care and time missed from work. Mr. Trump said the initiative would also hold organ procurement organizations more accountable so that fewer usable organs are discarded.
Trump said his plan would help 17,000 additional Americans get a kidney transplant each year by 2030. The policy would also help 11,000 more Americans get hearts, lungs, and livers annually.
Kidney transplants cost less than having patients spend years on dialysis, according to government figures. Dialysis treatment runs on average about $89,000 a year, while a kidney transplant surgery averages about $32,000 and postsurgery care runs about $25,000 per year. Mr. Trump estimated his plan would save families and taxpayers $4.2 billion a year. “This is a dramatic and long overdue reform,” he said.
In the United States, only about 12% of patients get dialysis at home, far lower than in other countries, Mr. Trump said. The plan calls for increasing that share to 80% by 2025.
Nichole Jefferson, 47 years, of Dallas, who is awaiting a second transplant to replace a transplanted kidney that is failing, said getting the treatment at home is much less taxing. She had home dialysis for 4 years before her initial transplant in 2008.
“It’s great to be at home where I was more comfortable and more relaxed and the care was in my hands,” she said in an interview at the Trump event. By getting dialysis at night while she slept, she was able to work during the day and take part in family events.
She had to go to a center for the dialysis when the home dialysis stopped working. “I was depressed to be in the center tied to a chair for 4 hours next to people I did not know,” she said. Patients often have dialysis several days a week.
Other patient advocates applauded Mr. Trump’s plan.
“The administration’s commitment to charting a new course for kidney health will help revolutionize transplantation and dialysis and advance new innovations, therapies and treatments, which patients everywhere have been waiting on for far too long,” said Kevin Longino, CEO of the National Kidney Foundation and a kidney transplant patient.
DaVita, the Denver-based company that is the largest provider of home dialysis in the country, offered a more muted response, saying it looked forward to working with the administration. The company’s stock, which fell in recent days ahead of the announcement, rose about 5% Wednesday.
Administration officials said many aspects of their plan would begin next year. Health providers in half the country will be required to participate in one of the new payment models in which they will face some financial risk for caring for patients. Doctors and health systems will have options to take on more financial risk, which means they could make more money or lose more money based on the health of their kidney patients.
Patients, however, will continue to be able to choose their doctors and dialysis providers.
Joe Grogan, head of the White House Domestic Policy Council, said the kidney disease issue “fits in the wheelhouse of items the president likes to confront. ... The current quality of outcomes are pathetic in this area.”
About half of patients on dialysis die within 5 years, Mr. Azar said.
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Type 2 diabetes is particularly devastating in adolescents
SAN FRANCISCO – and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.
“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”
In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.
Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.
“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”
Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).
In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A1c.
Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.
Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.
He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.
In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”
The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.
TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.
Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.
But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
Cardiovascular complications
The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.
Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
Decline renal function
In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.
So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
Pregnancy outcomes
Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.
There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.
Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.
In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.
Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.
In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A1c level of more than 8%.
Retinopathy
Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).
None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
Neuropathy
The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.
“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.
There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.
Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).
The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.
This article was updated 7/22/19.
SAN FRANCISCO – and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.
“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”
In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.
Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.
“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”
Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).
In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A1c.
Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.
Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.
He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.
In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”
The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.
TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.
Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.
But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
Cardiovascular complications
The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.
Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
Decline renal function
In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.
So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
Pregnancy outcomes
Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.
There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.
Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.
In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.
Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.
In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A1c level of more than 8%.
Retinopathy
Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).
None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
Neuropathy
The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.
“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.
There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.
Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).
The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.
This article was updated 7/22/19.
SAN FRANCISCO – and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.
“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”
In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.
Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.
“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”
Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).
In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A1c.
Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.
Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.
He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.
In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”
The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.
TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.
Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.
But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
Cardiovascular complications
The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.
Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
Decline renal function
In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.
So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
Pregnancy outcomes
Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.
There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.
Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.
In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.
Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.
In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A1c level of more than 8%.
Retinopathy
Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).
None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
Neuropathy
The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.
“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.
There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.
Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).
The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.
This article was updated 7/22/19.
EXPERT ANALYSIS FROM ADA 2019
SGLT2 inhibitors, GLP-1 RAs are effective, but costly in T2D
Metformin linked to lower dementia risk in black patients
Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.
The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).
Previous findings have suggested that black patients with type 2 diabetes face a 10%-18% higher risk of dementia, compared with white patients (Diabetes Care. 2014; 37[4]:1009-15). Another study linked type 2 diabetes in middle-aged black patients to a 41% decrease in cognition per test results over 14 years. There was no such decrease in white patients (Neuroepidemiology. 2014;43[3-4]: 220-7).
For the new study, researchers led by Jeffrey F. Scherrer, PhD, of Saint Louis University tracked 73,761 patients aged 50 years or older from 2000-2001 (when they were free of dementia and not taking diabetes) to 2015. Among the patients, 86% were white and 14% were black. In the white and black groups, 97% and 95% were men, respectively, and 61% and 55% were obese, respectively.
All participants began metformin (76%) or sulfonylurea (24%) monotherapy after the baseline period. Guidelines recommend metformin as a first-line treatment for type 2 diabetes, whereas sulfonylureas are considered second-line drugs that should be added to metformin.
After adjustment for confounders such as socioeconomic status and other medical conditions, the researchers found a significantly lower risk of dementia in black patients who took metformin, compared with those taking a sulfonylurea (hazard ratio, 0.73; 95% confidence interval, 0.6-0.89). There was no difference between the drugs among white patients (HR, 0.96; 95% CI, 0.9-1.03, both P = .008)
The results were not statistically significant among age groups, but there were trends. In black patients, the dementia-lowering benefit was largest among those aged 50-64 years (HR, 0.6; 95% CI, 0.45-0.81), followed by those aged 65-74 years (HR, 0.71; 95% CI, 0.53-0.94), and there was no benefit among those aged at least 75 (HR, 1.17; 95% CI, 0.73-1.85) all P = .055. There was a slight benefit among white patients in one of the age groups – 65-74 years (HR, 0.9; 95% CI, 0.82-0.99; P = .315).
The authors suggested that the findings could have been the result of an effect of metformin to reduce vascular disease and chronic inflammation in black patients.
They also noted that further research is needed to identify the demographic and clinical subgroups in which metformin is most strongly associated with a reduction in the risk of dementia. In addition, they emphasized that clinical trials are needed to confirm the study findings.
The National Institutes of Health funded the study. The authors report no relevant disclosures.
SOURCE: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.
Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.
The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).
Previous findings have suggested that black patients with type 2 diabetes face a 10%-18% higher risk of dementia, compared with white patients (Diabetes Care. 2014; 37[4]:1009-15). Another study linked type 2 diabetes in middle-aged black patients to a 41% decrease in cognition per test results over 14 years. There was no such decrease in white patients (Neuroepidemiology. 2014;43[3-4]: 220-7).
For the new study, researchers led by Jeffrey F. Scherrer, PhD, of Saint Louis University tracked 73,761 patients aged 50 years or older from 2000-2001 (when they were free of dementia and not taking diabetes) to 2015. Among the patients, 86% were white and 14% were black. In the white and black groups, 97% and 95% were men, respectively, and 61% and 55% were obese, respectively.
All participants began metformin (76%) or sulfonylurea (24%) monotherapy after the baseline period. Guidelines recommend metformin as a first-line treatment for type 2 diabetes, whereas sulfonylureas are considered second-line drugs that should be added to metformin.
After adjustment for confounders such as socioeconomic status and other medical conditions, the researchers found a significantly lower risk of dementia in black patients who took metformin, compared with those taking a sulfonylurea (hazard ratio, 0.73; 95% confidence interval, 0.6-0.89). There was no difference between the drugs among white patients (HR, 0.96; 95% CI, 0.9-1.03, both P = .008)
The results were not statistically significant among age groups, but there were trends. In black patients, the dementia-lowering benefit was largest among those aged 50-64 years (HR, 0.6; 95% CI, 0.45-0.81), followed by those aged 65-74 years (HR, 0.71; 95% CI, 0.53-0.94), and there was no benefit among those aged at least 75 (HR, 1.17; 95% CI, 0.73-1.85) all P = .055. There was a slight benefit among white patients in one of the age groups – 65-74 years (HR, 0.9; 95% CI, 0.82-0.99; P = .315).
The authors suggested that the findings could have been the result of an effect of metformin to reduce vascular disease and chronic inflammation in black patients.
They also noted that further research is needed to identify the demographic and clinical subgroups in which metformin is most strongly associated with a reduction in the risk of dementia. In addition, they emphasized that clinical trials are needed to confirm the study findings.
The National Institutes of Health funded the study. The authors report no relevant disclosures.
SOURCE: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.
Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.
The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).
Previous findings have suggested that black patients with type 2 diabetes face a 10%-18% higher risk of dementia, compared with white patients (Diabetes Care. 2014; 37[4]:1009-15). Another study linked type 2 diabetes in middle-aged black patients to a 41% decrease in cognition per test results over 14 years. There was no such decrease in white patients (Neuroepidemiology. 2014;43[3-4]: 220-7).
For the new study, researchers led by Jeffrey F. Scherrer, PhD, of Saint Louis University tracked 73,761 patients aged 50 years or older from 2000-2001 (when they were free of dementia and not taking diabetes) to 2015. Among the patients, 86% were white and 14% were black. In the white and black groups, 97% and 95% were men, respectively, and 61% and 55% were obese, respectively.
All participants began metformin (76%) or sulfonylurea (24%) monotherapy after the baseline period. Guidelines recommend metformin as a first-line treatment for type 2 diabetes, whereas sulfonylureas are considered second-line drugs that should be added to metformin.
After adjustment for confounders such as socioeconomic status and other medical conditions, the researchers found a significantly lower risk of dementia in black patients who took metformin, compared with those taking a sulfonylurea (hazard ratio, 0.73; 95% confidence interval, 0.6-0.89). There was no difference between the drugs among white patients (HR, 0.96; 95% CI, 0.9-1.03, both P = .008)
The results were not statistically significant among age groups, but there were trends. In black patients, the dementia-lowering benefit was largest among those aged 50-64 years (HR, 0.6; 95% CI, 0.45-0.81), followed by those aged 65-74 years (HR, 0.71; 95% CI, 0.53-0.94), and there was no benefit among those aged at least 75 (HR, 1.17; 95% CI, 0.73-1.85) all P = .055. There was a slight benefit among white patients in one of the age groups – 65-74 years (HR, 0.9; 95% CI, 0.82-0.99; P = .315).
The authors suggested that the findings could have been the result of an effect of metformin to reduce vascular disease and chronic inflammation in black patients.
They also noted that further research is needed to identify the demographic and clinical subgroups in which metformin is most strongly associated with a reduction in the risk of dementia. In addition, they emphasized that clinical trials are needed to confirm the study findings.
The National Institutes of Health funded the study. The authors report no relevant disclosures.
SOURCE: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.
FROM ANNALS OF FAMILY MEDICINE
Key clinical point:
Major finding: Metformin monotherapy, compared with sulfonylurea monotherapy, was linked to a significantly lower risk for dementia in black patients (HR, 0.73; 95% CI, 0.6-0.89), but not in white patients (HR, 0.96; 95% CI, 0.9-1.03; P = .008).
Study details: Retrospective analysis of 73,761 patients aged 50 years or older in the Veterans Health Administration system who were tracked from 2000-2001 to 2015 and began metformin or sulfonylurea monotherapy after baseline.
Disclosures: The National Institutes of Health funded the study. The authors report no relevant disclosures.
Source: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.
Microvascular disease: An independent and exacerbating risk factor for amputation
Individuals with microvascular disease (MVD) showed a significantly increased risk of lower limb amputation in the absence of peripheral artery disease (PAD), according to the results of a large database analysis published online in Circulation.
Furthermore, those who had both MVD and PAD had a greater than 20-fold increased risk of amputation than if they had either PAD or MVD alone, according to Joshua A. Beckman, MD, of Vanderbilt University, Nashville, Tenn., and colleagues.
“The novelty of these findings becomes clear when put into the current framework of critical limb ischemia,” they wrote.
“In a recent state of the art review of [critical limb ischemia], MVD as a whole or its components did not receive a single mention. Our work shows that MVD helps identify a population not previously considered at particularly high risk for amputation and, when added to PAD, identify a group of patients at very high risk for amputation,” they continued.
Dr. Beckman and colleagues assessed individuals in the Veterans Aging Cohort Study (VACS), a prospective longitudinal cohort of veterans. They included all VACS participants who were alive as of April 1, 2003 with the baseline as a participant’s first clinic visit on or after this date. Participants were followed from baseline to the minimum of: date of lower extremity amputation, death, or Dec. 31, 2014.
They assessed four levels of vascular involvement: neither MVD nor PAD, MVD alone, PAD alone, and MVD plus PAD, with the primary outcome being lower limb amputation, all based on a variety of measures including appropriate ICD-9 or CPT codes.
The rate of incident amputation over a median of 9.3 years of follow-up was 1.16 per 1000 person-years. At the time of amputation, retinopathy was present in 69%, nephropathy in 67%, and neuropathy in 78% of participants.
After multivariable adjustment for 216 demographic characteristics, cardiovascular disease risk factors, and other potential confounders, they found that, compared with participants without either vascular disease, the presence of MVD alone was associated with a 3.7-fold increased risk of amputation, PAD alone conferred a 13.9-fold elevated risk of amputation, and the combination of PAD and MVD was associated with a 22.7-fold increased risk of amputation.
They also found that the location of amputation also varied depending on the type of vascular disease at the time of amputation.
Participants with MVD alone accounted for 18% of all amputations, 21% of below ankle amputations, 15% of below knee amputations, and 6% of all above knee amputations. Participants with PAD alone accounted for 22% of all amputations, 17% of below ankle, 25% of below knee, and 39% of above knee amputations. The combination of MVD and PAD accounted for 45% of all amputation and caused the most amputation at all limb levels. In addition, they found a statistically significant variation in vascular involvement and level of amputation, with MVD more likely to cause a below-ankle amputation and PAD more likely to cause below- and above-knee amputations (P less than .001)
“MVD likely participates importantly in the development of adverse limb events in PAD and suggests additional patient populations who may benefit from greater foot surveillance to minimize amputation,” the researchers concluded.
The study was supported by grants from the American Heart Association. Dr. Beckman reported consulting for multiple pharmaceutical companies and serving on the DSMC for Bayer and Novartis.
SOURCE: Beckman JA et al. Circulation. 2019. doi: 10.1161/CIRCULATIONAHA.119.040672.
Individuals with microvascular disease (MVD) showed a significantly increased risk of lower limb amputation in the absence of peripheral artery disease (PAD), according to the results of a large database analysis published online in Circulation.
Furthermore, those who had both MVD and PAD had a greater than 20-fold increased risk of amputation than if they had either PAD or MVD alone, according to Joshua A. Beckman, MD, of Vanderbilt University, Nashville, Tenn., and colleagues.
“The novelty of these findings becomes clear when put into the current framework of critical limb ischemia,” they wrote.
“In a recent state of the art review of [critical limb ischemia], MVD as a whole or its components did not receive a single mention. Our work shows that MVD helps identify a population not previously considered at particularly high risk for amputation and, when added to PAD, identify a group of patients at very high risk for amputation,” they continued.
Dr. Beckman and colleagues assessed individuals in the Veterans Aging Cohort Study (VACS), a prospective longitudinal cohort of veterans. They included all VACS participants who were alive as of April 1, 2003 with the baseline as a participant’s first clinic visit on or after this date. Participants were followed from baseline to the minimum of: date of lower extremity amputation, death, or Dec. 31, 2014.
They assessed four levels of vascular involvement: neither MVD nor PAD, MVD alone, PAD alone, and MVD plus PAD, with the primary outcome being lower limb amputation, all based on a variety of measures including appropriate ICD-9 or CPT codes.
The rate of incident amputation over a median of 9.3 years of follow-up was 1.16 per 1000 person-years. At the time of amputation, retinopathy was present in 69%, nephropathy in 67%, and neuropathy in 78% of participants.
After multivariable adjustment for 216 demographic characteristics, cardiovascular disease risk factors, and other potential confounders, they found that, compared with participants without either vascular disease, the presence of MVD alone was associated with a 3.7-fold increased risk of amputation, PAD alone conferred a 13.9-fold elevated risk of amputation, and the combination of PAD and MVD was associated with a 22.7-fold increased risk of amputation.
They also found that the location of amputation also varied depending on the type of vascular disease at the time of amputation.
Participants with MVD alone accounted for 18% of all amputations, 21% of below ankle amputations, 15% of below knee amputations, and 6% of all above knee amputations. Participants with PAD alone accounted for 22% of all amputations, 17% of below ankle, 25% of below knee, and 39% of above knee amputations. The combination of MVD and PAD accounted for 45% of all amputation and caused the most amputation at all limb levels. In addition, they found a statistically significant variation in vascular involvement and level of amputation, with MVD more likely to cause a below-ankle amputation and PAD more likely to cause below- and above-knee amputations (P less than .001)
“MVD likely participates importantly in the development of adverse limb events in PAD and suggests additional patient populations who may benefit from greater foot surveillance to minimize amputation,” the researchers concluded.
The study was supported by grants from the American Heart Association. Dr. Beckman reported consulting for multiple pharmaceutical companies and serving on the DSMC for Bayer and Novartis.
SOURCE: Beckman JA et al. Circulation. 2019. doi: 10.1161/CIRCULATIONAHA.119.040672.
Individuals with microvascular disease (MVD) showed a significantly increased risk of lower limb amputation in the absence of peripheral artery disease (PAD), according to the results of a large database analysis published online in Circulation.
Furthermore, those who had both MVD and PAD had a greater than 20-fold increased risk of amputation than if they had either PAD or MVD alone, according to Joshua A. Beckman, MD, of Vanderbilt University, Nashville, Tenn., and colleagues.
“The novelty of these findings becomes clear when put into the current framework of critical limb ischemia,” they wrote.
“In a recent state of the art review of [critical limb ischemia], MVD as a whole or its components did not receive a single mention. Our work shows that MVD helps identify a population not previously considered at particularly high risk for amputation and, when added to PAD, identify a group of patients at very high risk for amputation,” they continued.
Dr. Beckman and colleagues assessed individuals in the Veterans Aging Cohort Study (VACS), a prospective longitudinal cohort of veterans. They included all VACS participants who were alive as of April 1, 2003 with the baseline as a participant’s first clinic visit on or after this date. Participants were followed from baseline to the minimum of: date of lower extremity amputation, death, or Dec. 31, 2014.
They assessed four levels of vascular involvement: neither MVD nor PAD, MVD alone, PAD alone, and MVD plus PAD, with the primary outcome being lower limb amputation, all based on a variety of measures including appropriate ICD-9 or CPT codes.
The rate of incident amputation over a median of 9.3 years of follow-up was 1.16 per 1000 person-years. At the time of amputation, retinopathy was present in 69%, nephropathy in 67%, and neuropathy in 78% of participants.
After multivariable adjustment for 216 demographic characteristics, cardiovascular disease risk factors, and other potential confounders, they found that, compared with participants without either vascular disease, the presence of MVD alone was associated with a 3.7-fold increased risk of amputation, PAD alone conferred a 13.9-fold elevated risk of amputation, and the combination of PAD and MVD was associated with a 22.7-fold increased risk of amputation.
They also found that the location of amputation also varied depending on the type of vascular disease at the time of amputation.
Participants with MVD alone accounted for 18% of all amputations, 21% of below ankle amputations, 15% of below knee amputations, and 6% of all above knee amputations. Participants with PAD alone accounted for 22% of all amputations, 17% of below ankle, 25% of below knee, and 39% of above knee amputations. The combination of MVD and PAD accounted for 45% of all amputation and caused the most amputation at all limb levels. In addition, they found a statistically significant variation in vascular involvement and level of amputation, with MVD more likely to cause a below-ankle amputation and PAD more likely to cause below- and above-knee amputations (P less than .001)
“MVD likely participates importantly in the development of adverse limb events in PAD and suggests additional patient populations who may benefit from greater foot surveillance to minimize amputation,” the researchers concluded.
The study was supported by grants from the American Heart Association. Dr. Beckman reported consulting for multiple pharmaceutical companies and serving on the DSMC for Bayer and Novartis.
SOURCE: Beckman JA et al. Circulation. 2019. doi: 10.1161/CIRCULATIONAHA.119.040672.
FROM CIRCULATION
Key clinical point: Microvascular disease yielded a 3.7-fold increased risk of lower limb amputation.
Major finding:
Study details: Database analysis of 125,674 participants in the Veterans Aging Cohort Study from April 2003 through December 2014.
Disclosures: The study was supported by grants from the American Heart Association. Dr. Beckman reported consulting for multiple pharmaceutical companies and serving on the DSMC for Bayer and Novartis.
Source: Beckman JA et al. Circulation. 2019. doi: 10.1161/CIRCULATIONAHA.119.040672.
Mortality caused by chronic liver disease in setting of diabetes continues to rise
results from a large database analysis showed.
“While diabetes-related mortality has been reported to be decreasing due to improved awareness and management, our results highlight the need to better address NAFLD [nonalcoholic fatty liver disease] and end-stage liver disease among individuals with diabetes,” researchers led by Donghee Kim, MD, PhD, wrote in an article published in Clinical Gastroenterology and Hepatology.
In an effort to estimate the trends in chronic liver disease–related mortality among individuals with diabetes from 2007 to 2017 in the United States, Dr. Kim, of the division of gastroenterology and hepatology at Stanford (Calif.) University, and colleagues analyzed mortality records from the National Vital Statistic System database. They calculated age-specific mortality by dividing the number of deaths by the total U.S. census population for each year and standardized them according to age distribution of 2010 U.S. standard population. The researchers used joinpoint regression analysis to determine trends.
Of 2,686,590 individuals with diabetes identified, 48,761 had chronic liver disease as the underlying cause of death listed on the death certificate. Among individuals who had diabetes listed on their death certificate, the age-standardized mortality for cirrhosis and hepatocellular carcinoma as an underlying cause of death increased with an annual rate of 1.2% and 1.9%, respectively. Based on etiology, age-standardized mortality for hepatitis C and hepatitis B viral infections decreased at an annual rate of 4.4% and 5.1%, respectively. On the other hand, mortality among individuals with NAFLD and alcoholic liver disease increased at annual rates of 11.6% and 1.4%, respectively.
“When we defined chronic liver disease as an underlying or contributing cause of death among individuals with diabetes listed on the death certificate, the overall results remained similar,” the researchers wrote. They acknowledged certain limitations of the analysis, including the fact that using death certificates and ICD-10 codes “has the potential for misclassification and underestimation for diabetes and chronic liver disease–related mortality. However, the coding method has been constant over time, so it is unlikely to account for present trends. Increasing obesity and associated insulin resistance likely explain the link between diabetes and NAFLD and end-stage liver disease through hepatic inflammation and various proinflammatory cytokines.”
One of the study authors was supported by the National Institutes of Health. None of the other authors reported having relevant disclosures.
SOURCE: Kim D et al. Clin Gastroenterol Hepatol. 2019 Jun 17. doi: 10.1016/j.cgh.2019.06.011.
results from a large database analysis showed.
“While diabetes-related mortality has been reported to be decreasing due to improved awareness and management, our results highlight the need to better address NAFLD [nonalcoholic fatty liver disease] and end-stage liver disease among individuals with diabetes,” researchers led by Donghee Kim, MD, PhD, wrote in an article published in Clinical Gastroenterology and Hepatology.
In an effort to estimate the trends in chronic liver disease–related mortality among individuals with diabetes from 2007 to 2017 in the United States, Dr. Kim, of the division of gastroenterology and hepatology at Stanford (Calif.) University, and colleagues analyzed mortality records from the National Vital Statistic System database. They calculated age-specific mortality by dividing the number of deaths by the total U.S. census population for each year and standardized them according to age distribution of 2010 U.S. standard population. The researchers used joinpoint regression analysis to determine trends.
Of 2,686,590 individuals with diabetes identified, 48,761 had chronic liver disease as the underlying cause of death listed on the death certificate. Among individuals who had diabetes listed on their death certificate, the age-standardized mortality for cirrhosis and hepatocellular carcinoma as an underlying cause of death increased with an annual rate of 1.2% and 1.9%, respectively. Based on etiology, age-standardized mortality for hepatitis C and hepatitis B viral infections decreased at an annual rate of 4.4% and 5.1%, respectively. On the other hand, mortality among individuals with NAFLD and alcoholic liver disease increased at annual rates of 11.6% and 1.4%, respectively.
“When we defined chronic liver disease as an underlying or contributing cause of death among individuals with diabetes listed on the death certificate, the overall results remained similar,” the researchers wrote. They acknowledged certain limitations of the analysis, including the fact that using death certificates and ICD-10 codes “has the potential for misclassification and underestimation for diabetes and chronic liver disease–related mortality. However, the coding method has been constant over time, so it is unlikely to account for present trends. Increasing obesity and associated insulin resistance likely explain the link between diabetes and NAFLD and end-stage liver disease through hepatic inflammation and various proinflammatory cytokines.”
One of the study authors was supported by the National Institutes of Health. None of the other authors reported having relevant disclosures.
SOURCE: Kim D et al. Clin Gastroenterol Hepatol. 2019 Jun 17. doi: 10.1016/j.cgh.2019.06.011.
results from a large database analysis showed.
“While diabetes-related mortality has been reported to be decreasing due to improved awareness and management, our results highlight the need to better address NAFLD [nonalcoholic fatty liver disease] and end-stage liver disease among individuals with diabetes,” researchers led by Donghee Kim, MD, PhD, wrote in an article published in Clinical Gastroenterology and Hepatology.
In an effort to estimate the trends in chronic liver disease–related mortality among individuals with diabetes from 2007 to 2017 in the United States, Dr. Kim, of the division of gastroenterology and hepatology at Stanford (Calif.) University, and colleagues analyzed mortality records from the National Vital Statistic System database. They calculated age-specific mortality by dividing the number of deaths by the total U.S. census population for each year and standardized them according to age distribution of 2010 U.S. standard population. The researchers used joinpoint regression analysis to determine trends.
Of 2,686,590 individuals with diabetes identified, 48,761 had chronic liver disease as the underlying cause of death listed on the death certificate. Among individuals who had diabetes listed on their death certificate, the age-standardized mortality for cirrhosis and hepatocellular carcinoma as an underlying cause of death increased with an annual rate of 1.2% and 1.9%, respectively. Based on etiology, age-standardized mortality for hepatitis C and hepatitis B viral infections decreased at an annual rate of 4.4% and 5.1%, respectively. On the other hand, mortality among individuals with NAFLD and alcoholic liver disease increased at annual rates of 11.6% and 1.4%, respectively.
“When we defined chronic liver disease as an underlying or contributing cause of death among individuals with diabetes listed on the death certificate, the overall results remained similar,” the researchers wrote. They acknowledged certain limitations of the analysis, including the fact that using death certificates and ICD-10 codes “has the potential for misclassification and underestimation for diabetes and chronic liver disease–related mortality. However, the coding method has been constant over time, so it is unlikely to account for present trends. Increasing obesity and associated insulin resistance likely explain the link between diabetes and NAFLD and end-stage liver disease through hepatic inflammation and various proinflammatory cytokines.”
One of the study authors was supported by the National Institutes of Health. None of the other authors reported having relevant disclosures.
SOURCE: Kim D et al. Clin Gastroenterol Hepatol. 2019 Jun 17. doi: 10.1016/j.cgh.2019.06.011.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
SGLT2 inhibitors for type 1 diabetes: Doctors debate the merits
SAN FRANCISCO – At first, the diabetes professionals in the audience at the annual scientific sessions of the American Diabetes Association overwhelmingly raised their hands to say they would support using SGLT2 inhibitors as adjunctive therapy in patients with type 1 diabetes. Then two physicians debated whether the drugs were too risky – predictably, one said yes, the other said no. In the end, most of the audience was unconvinced by one of the doctors. Which one? Well, we’ll get to that.
First, let’s look at the issue that divided the two physicians: Should the sodium-glucose cotransporter 2 (SGLT2) inhibitors canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) – now commonly used to treat patients with type 2 diabetes – also be prescribed for patients with type 1 diabetes?
The drugs are not cleared in the United States for use in patients with type 1 diabetes, although drug makers are seeking approval. Earlier in 2019, the Food and Drug Administration turned down a request for the approval of sotagliflozin (Zynquista), a dual SGLT1 and SGLT2 inhibitor, for adults with type 1 diabetes. However, the drug has been approved in the European Union for certain overweight patients with type 1 diabetes.
In addition, the drugs are very costly, compared with some of the other diabetes medications, and physicians say that puts them out of reach for some patients.
The case for ...
In arguing that SGLT2 inhibitors would be appropriate as a therapy for patients with type 1 diabetes, Bruce A. Perkins, MD, MPH, professor and clinician-scientist at Leadership Sinai Center for Diabetes at the University of Toronto, emphasized the need for new treatments in type 1 diabetes.
“Even today, people with type 1 tell us they feel isolated, they fear hypoglycemia, they fear complications. And they have this undue burden of self-management,” he said. “We can do much better. Insulin therapy still needs us desperately needing more.”
Dr. Perkins highlighted the drugs’ widely lauded effects on cardiac and renal health and noted that a 2019 meta-analysis of 10 trials found that, compared with placebo, the drugs were associated with mean reductions in hemoglobin A1c (–0.39%; 95% confidence interval, –0.43 to –0.36) and body weight (–3.47%; 95% CI, –3.78 to –3.16).
That analysis also showed a higher risk of genital infection (3.57; 95% CI, 2.97-4.29) and diabetic ketoacidosis (DKA; 3.11; 95% CI, 2.11-4.58) with SGLT inhibitors, but the authors concluded that, despite the adverse events, the available data suggested that adding the inhibitors to basal insulin could be beneficial in patients with type 1 diabetes (Diabetes Metab Res Rev. 2019 Apr 11. doi: 10.1002/dmrr.3169).
In reference to the findings on DKA, Dr. Perkins said recent research has suggested that the DKA risk could be lowered by decreasing the dose of the SGLT2 inhibitors. “[DKA] is a problem, there’s no question, but there’s a background population risk. Whether we introduce an SGLT2 or not, we have to deal with this issue. We can deal with and overcome the excess DKA risk.”
In the big picture, he said, “it would be a crime not to make this treatment available to some patients. Meaningful benefits far outweigh the risks.”
The case against ...
On the other side of the debate was David M. Nathan, MD, of Harvard Medical School and the Clinical Research Center and Diabetes Center at Massachusetts General Hospital, Boston, who acknowledged the benefits of the SGLT2 inhibitors in type 2 diabetes.
However, he pointed to findings from a 2015 trial of canagliflozin as an add-on in type 1 diabetes (Diabetes Care. 2015;38[12]:2258-65). In that 18-week, randomized phase 2 trial, the investigators found that patients who took the drug had significantly higher rates of serious adverse events (7.7% or 6.8%, depending on dose, vs. 0% for placebo), urinary tract infections (4.3% and 5.1% vs. 1.7%), and DKA (4.3% and 6.0% vs. 0%).
“It would have cost $400 a month for the ‘pleasure’ of those side effects,” Dr. Nathan said.
He also noted a 2015 report on a 29-day, randomized, placebo-controlled study of sotagliflozin, the dual SGLT1 and SGLT2 inhibitor drug, as an add-on treatment for type 1 diabetes, in which investigators reported two episodes of DKA (13%) in the SGLT2 group, compared with none in placebo (Diabetes Care. 2015;38[7]:1181-8).
Dr. Nathan also pointed to a recent FDA warning about cases of Fournier gangrene, a rare type of serious genital infection, in patients taking SGLT2 inhibitors.
“To me, the risk [of using SGLT2 inhibitors in type 1 diabetes] outweighs the benefit by a lot,” he said, echoing comments he made in an editorial he wrote in 2017, that “any added benefits of adjunctive therapies for type 1 diabetes must be carefully balanced against their added risk and cost. Physicians and patients should beware” (N Engl J Med. 2017; 377:2390-1).
The outcome...
The audience was not sufficiently convinced by Dr. Nathan to swing the final vote fully in his favor, but he did manage to dent the initial support for using SGLT2 inhibitors in patients with type 1 disease. Before the debate, the show of hands suggested that roughly 80% of the audience thought SGLT2 inhibitors would be an appropriate therapy option for patients with type 1 diabetes. When the moderator asked the same question again after the arguments had been presented, that initial support had been eroded to about 70%. Dr. Nathan had clearly raised some doubts among the attendees, but Dr. Perkins’ perspective prevailed.
Dr. Perkins reported speaker fees from Medtronic, Abbott, Sanofi and Lilly; advisory panel service for Abbott, Boehringer Ingelheim, and Insulet; and research support to his institution from Boehringer Ingelheim and Bank of Montreal. Dr. Nathan reports no disclosures.
SAN FRANCISCO – At first, the diabetes professionals in the audience at the annual scientific sessions of the American Diabetes Association overwhelmingly raised their hands to say they would support using SGLT2 inhibitors as adjunctive therapy in patients with type 1 diabetes. Then two physicians debated whether the drugs were too risky – predictably, one said yes, the other said no. In the end, most of the audience was unconvinced by one of the doctors. Which one? Well, we’ll get to that.
First, let’s look at the issue that divided the two physicians: Should the sodium-glucose cotransporter 2 (SGLT2) inhibitors canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) – now commonly used to treat patients with type 2 diabetes – also be prescribed for patients with type 1 diabetes?
The drugs are not cleared in the United States for use in patients with type 1 diabetes, although drug makers are seeking approval. Earlier in 2019, the Food and Drug Administration turned down a request for the approval of sotagliflozin (Zynquista), a dual SGLT1 and SGLT2 inhibitor, for adults with type 1 diabetes. However, the drug has been approved in the European Union for certain overweight patients with type 1 diabetes.
In addition, the drugs are very costly, compared with some of the other diabetes medications, and physicians say that puts them out of reach for some patients.
The case for ...
In arguing that SGLT2 inhibitors would be appropriate as a therapy for patients with type 1 diabetes, Bruce A. Perkins, MD, MPH, professor and clinician-scientist at Leadership Sinai Center for Diabetes at the University of Toronto, emphasized the need for new treatments in type 1 diabetes.
“Even today, people with type 1 tell us they feel isolated, they fear hypoglycemia, they fear complications. And they have this undue burden of self-management,” he said. “We can do much better. Insulin therapy still needs us desperately needing more.”
Dr. Perkins highlighted the drugs’ widely lauded effects on cardiac and renal health and noted that a 2019 meta-analysis of 10 trials found that, compared with placebo, the drugs were associated with mean reductions in hemoglobin A1c (–0.39%; 95% confidence interval, –0.43 to –0.36) and body weight (–3.47%; 95% CI, –3.78 to –3.16).
That analysis also showed a higher risk of genital infection (3.57; 95% CI, 2.97-4.29) and diabetic ketoacidosis (DKA; 3.11; 95% CI, 2.11-4.58) with SGLT inhibitors, but the authors concluded that, despite the adverse events, the available data suggested that adding the inhibitors to basal insulin could be beneficial in patients with type 1 diabetes (Diabetes Metab Res Rev. 2019 Apr 11. doi: 10.1002/dmrr.3169).
In reference to the findings on DKA, Dr. Perkins said recent research has suggested that the DKA risk could be lowered by decreasing the dose of the SGLT2 inhibitors. “[DKA] is a problem, there’s no question, but there’s a background population risk. Whether we introduce an SGLT2 or not, we have to deal with this issue. We can deal with and overcome the excess DKA risk.”
In the big picture, he said, “it would be a crime not to make this treatment available to some patients. Meaningful benefits far outweigh the risks.”
The case against ...
On the other side of the debate was David M. Nathan, MD, of Harvard Medical School and the Clinical Research Center and Diabetes Center at Massachusetts General Hospital, Boston, who acknowledged the benefits of the SGLT2 inhibitors in type 2 diabetes.
However, he pointed to findings from a 2015 trial of canagliflozin as an add-on in type 1 diabetes (Diabetes Care. 2015;38[12]:2258-65). In that 18-week, randomized phase 2 trial, the investigators found that patients who took the drug had significantly higher rates of serious adverse events (7.7% or 6.8%, depending on dose, vs. 0% for placebo), urinary tract infections (4.3% and 5.1% vs. 1.7%), and DKA (4.3% and 6.0% vs. 0%).
“It would have cost $400 a month for the ‘pleasure’ of those side effects,” Dr. Nathan said.
He also noted a 2015 report on a 29-day, randomized, placebo-controlled study of sotagliflozin, the dual SGLT1 and SGLT2 inhibitor drug, as an add-on treatment for type 1 diabetes, in which investigators reported two episodes of DKA (13%) in the SGLT2 group, compared with none in placebo (Diabetes Care. 2015;38[7]:1181-8).
Dr. Nathan also pointed to a recent FDA warning about cases of Fournier gangrene, a rare type of serious genital infection, in patients taking SGLT2 inhibitors.
“To me, the risk [of using SGLT2 inhibitors in type 1 diabetes] outweighs the benefit by a lot,” he said, echoing comments he made in an editorial he wrote in 2017, that “any added benefits of adjunctive therapies for type 1 diabetes must be carefully balanced against their added risk and cost. Physicians and patients should beware” (N Engl J Med. 2017; 377:2390-1).
The outcome...
The audience was not sufficiently convinced by Dr. Nathan to swing the final vote fully in his favor, but he did manage to dent the initial support for using SGLT2 inhibitors in patients with type 1 disease. Before the debate, the show of hands suggested that roughly 80% of the audience thought SGLT2 inhibitors would be an appropriate therapy option for patients with type 1 diabetes. When the moderator asked the same question again after the arguments had been presented, that initial support had been eroded to about 70%. Dr. Nathan had clearly raised some doubts among the attendees, but Dr. Perkins’ perspective prevailed.
Dr. Perkins reported speaker fees from Medtronic, Abbott, Sanofi and Lilly; advisory panel service for Abbott, Boehringer Ingelheim, and Insulet; and research support to his institution from Boehringer Ingelheim and Bank of Montreal. Dr. Nathan reports no disclosures.
SAN FRANCISCO – At first, the diabetes professionals in the audience at the annual scientific sessions of the American Diabetes Association overwhelmingly raised their hands to say they would support using SGLT2 inhibitors as adjunctive therapy in patients with type 1 diabetes. Then two physicians debated whether the drugs were too risky – predictably, one said yes, the other said no. In the end, most of the audience was unconvinced by one of the doctors. Which one? Well, we’ll get to that.
First, let’s look at the issue that divided the two physicians: Should the sodium-glucose cotransporter 2 (SGLT2) inhibitors canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) – now commonly used to treat patients with type 2 diabetes – also be prescribed for patients with type 1 diabetes?
The drugs are not cleared in the United States for use in patients with type 1 diabetes, although drug makers are seeking approval. Earlier in 2019, the Food and Drug Administration turned down a request for the approval of sotagliflozin (Zynquista), a dual SGLT1 and SGLT2 inhibitor, for adults with type 1 diabetes. However, the drug has been approved in the European Union for certain overweight patients with type 1 diabetes.
In addition, the drugs are very costly, compared with some of the other diabetes medications, and physicians say that puts them out of reach for some patients.
The case for ...
In arguing that SGLT2 inhibitors would be appropriate as a therapy for patients with type 1 diabetes, Bruce A. Perkins, MD, MPH, professor and clinician-scientist at Leadership Sinai Center for Diabetes at the University of Toronto, emphasized the need for new treatments in type 1 diabetes.
“Even today, people with type 1 tell us they feel isolated, they fear hypoglycemia, they fear complications. And they have this undue burden of self-management,” he said. “We can do much better. Insulin therapy still needs us desperately needing more.”
Dr. Perkins highlighted the drugs’ widely lauded effects on cardiac and renal health and noted that a 2019 meta-analysis of 10 trials found that, compared with placebo, the drugs were associated with mean reductions in hemoglobin A1c (–0.39%; 95% confidence interval, –0.43 to –0.36) and body weight (–3.47%; 95% CI, –3.78 to –3.16).
That analysis also showed a higher risk of genital infection (3.57; 95% CI, 2.97-4.29) and diabetic ketoacidosis (DKA; 3.11; 95% CI, 2.11-4.58) with SGLT inhibitors, but the authors concluded that, despite the adverse events, the available data suggested that adding the inhibitors to basal insulin could be beneficial in patients with type 1 diabetes (Diabetes Metab Res Rev. 2019 Apr 11. doi: 10.1002/dmrr.3169).
In reference to the findings on DKA, Dr. Perkins said recent research has suggested that the DKA risk could be lowered by decreasing the dose of the SGLT2 inhibitors. “[DKA] is a problem, there’s no question, but there’s a background population risk. Whether we introduce an SGLT2 or not, we have to deal with this issue. We can deal with and overcome the excess DKA risk.”
In the big picture, he said, “it would be a crime not to make this treatment available to some patients. Meaningful benefits far outweigh the risks.”
The case against ...
On the other side of the debate was David M. Nathan, MD, of Harvard Medical School and the Clinical Research Center and Diabetes Center at Massachusetts General Hospital, Boston, who acknowledged the benefits of the SGLT2 inhibitors in type 2 diabetes.
However, he pointed to findings from a 2015 trial of canagliflozin as an add-on in type 1 diabetes (Diabetes Care. 2015;38[12]:2258-65). In that 18-week, randomized phase 2 trial, the investigators found that patients who took the drug had significantly higher rates of serious adverse events (7.7% or 6.8%, depending on dose, vs. 0% for placebo), urinary tract infections (4.3% and 5.1% vs. 1.7%), and DKA (4.3% and 6.0% vs. 0%).
“It would have cost $400 a month for the ‘pleasure’ of those side effects,” Dr. Nathan said.
He also noted a 2015 report on a 29-day, randomized, placebo-controlled study of sotagliflozin, the dual SGLT1 and SGLT2 inhibitor drug, as an add-on treatment for type 1 diabetes, in which investigators reported two episodes of DKA (13%) in the SGLT2 group, compared with none in placebo (Diabetes Care. 2015;38[7]:1181-8).
Dr. Nathan also pointed to a recent FDA warning about cases of Fournier gangrene, a rare type of serious genital infection, in patients taking SGLT2 inhibitors.
“To me, the risk [of using SGLT2 inhibitors in type 1 diabetes] outweighs the benefit by a lot,” he said, echoing comments he made in an editorial he wrote in 2017, that “any added benefits of adjunctive therapies for type 1 diabetes must be carefully balanced against their added risk and cost. Physicians and patients should beware” (N Engl J Med. 2017; 377:2390-1).
The outcome...
The audience was not sufficiently convinced by Dr. Nathan to swing the final vote fully in his favor, but he did manage to dent the initial support for using SGLT2 inhibitors in patients with type 1 disease. Before the debate, the show of hands suggested that roughly 80% of the audience thought SGLT2 inhibitors would be an appropriate therapy option for patients with type 1 diabetes. When the moderator asked the same question again after the arguments had been presented, that initial support had been eroded to about 70%. Dr. Nathan had clearly raised some doubts among the attendees, but Dr. Perkins’ perspective prevailed.
Dr. Perkins reported speaker fees from Medtronic, Abbott, Sanofi and Lilly; advisory panel service for Abbott, Boehringer Ingelheim, and Insulet; and research support to his institution from Boehringer Ingelheim and Bank of Montreal. Dr. Nathan reports no disclosures.
EXPERT ANALYSIS FROM ADA 2019
VOC-sniffing necklace may support early detection of hypoglycemia
SAN FRANCISCO – according to investigators from Indiana University-Purdue University, Indianapolis.
The device would detect changes in the volatile organic compounds (VOCs) that patients exhale as their plasma glucose level drops. In an insulin clamp study in 11 people with type 1 diabetes, the Indianapolis team found a marked shift in VOCs at a plasma glucose level of 90 mg/dL that persisted all the way down to a level of 50 mg/dL.
The team is now working on a sensor to detect that shift and alert patients. It’s the same trick that diabetes alert dogs do – minus the pup.
The device would be worn like a necklace, and “sense the air around your breath every 15 minutes or so,” said lead investigator Amanda P. Siegel, PhD, an analytical chemist and assistant research professor at the university.
Some continuous glucose monitors already warn of impending hypoglycemia, but the interstitial glucose levels on which they rely lag behind plasma glucose level by about 15 minutes or so. A VOC sniffer offers the hope of a real-time warning, Dr. Siegel said at the annual scientific sessions of the American Diabetes Association.
The team used gas chromatography–mass spectrometry to analyze 94 breath samples from the 11 participants, starting at a median fasting plasma glucose level of 150 mg/dL all the way down to 50 mg/dL, and back up to recovery. Samples collected at the 90-mg/dL and 80-mg/dL levels demonstrated VOC concentrations very similar to those at and below the hypoglycemia threshold of 70 mg/dL.
Even at 90 mg/dL, the VOC profile “looked like patients were already low. These volatile compounds change early” and stay on the breath as plasma glucose drops. “They are different from normal levels for the entire time, and separate out nicely,” Dr. Siegel said.
The team is not saying which volatile compounds are involved while the sensor is under development. They are looking for funding, and if all goes well, they hope to submit a device application to the Food and Drug Administration in 2020.
Other teams are also looking to VOCs to replace poor Fido, but he can alert to hyperglycemia and other problems as well, so his job is safe for now.
The work has been supported by the National Science Foundation. Dr. Siegel did not have any disclosures.
SOURCE: Siegel AP et al. ADA 2019, Abstract 968-P.
SAN FRANCISCO – according to investigators from Indiana University-Purdue University, Indianapolis.
The device would detect changes in the volatile organic compounds (VOCs) that patients exhale as their plasma glucose level drops. In an insulin clamp study in 11 people with type 1 diabetes, the Indianapolis team found a marked shift in VOCs at a plasma glucose level of 90 mg/dL that persisted all the way down to a level of 50 mg/dL.
The team is now working on a sensor to detect that shift and alert patients. It’s the same trick that diabetes alert dogs do – minus the pup.
The device would be worn like a necklace, and “sense the air around your breath every 15 minutes or so,” said lead investigator Amanda P. Siegel, PhD, an analytical chemist and assistant research professor at the university.
Some continuous glucose monitors already warn of impending hypoglycemia, but the interstitial glucose levels on which they rely lag behind plasma glucose level by about 15 minutes or so. A VOC sniffer offers the hope of a real-time warning, Dr. Siegel said at the annual scientific sessions of the American Diabetes Association.
The team used gas chromatography–mass spectrometry to analyze 94 breath samples from the 11 participants, starting at a median fasting plasma glucose level of 150 mg/dL all the way down to 50 mg/dL, and back up to recovery. Samples collected at the 90-mg/dL and 80-mg/dL levels demonstrated VOC concentrations very similar to those at and below the hypoglycemia threshold of 70 mg/dL.
Even at 90 mg/dL, the VOC profile “looked like patients were already low. These volatile compounds change early” and stay on the breath as plasma glucose drops. “They are different from normal levels for the entire time, and separate out nicely,” Dr. Siegel said.
The team is not saying which volatile compounds are involved while the sensor is under development. They are looking for funding, and if all goes well, they hope to submit a device application to the Food and Drug Administration in 2020.
Other teams are also looking to VOCs to replace poor Fido, but he can alert to hyperglycemia and other problems as well, so his job is safe for now.
The work has been supported by the National Science Foundation. Dr. Siegel did not have any disclosures.
SOURCE: Siegel AP et al. ADA 2019, Abstract 968-P.
SAN FRANCISCO – according to investigators from Indiana University-Purdue University, Indianapolis.
The device would detect changes in the volatile organic compounds (VOCs) that patients exhale as their plasma glucose level drops. In an insulin clamp study in 11 people with type 1 diabetes, the Indianapolis team found a marked shift in VOCs at a plasma glucose level of 90 mg/dL that persisted all the way down to a level of 50 mg/dL.
The team is now working on a sensor to detect that shift and alert patients. It’s the same trick that diabetes alert dogs do – minus the pup.
The device would be worn like a necklace, and “sense the air around your breath every 15 minutes or so,” said lead investigator Amanda P. Siegel, PhD, an analytical chemist and assistant research professor at the university.
Some continuous glucose monitors already warn of impending hypoglycemia, but the interstitial glucose levels on which they rely lag behind plasma glucose level by about 15 minutes or so. A VOC sniffer offers the hope of a real-time warning, Dr. Siegel said at the annual scientific sessions of the American Diabetes Association.
The team used gas chromatography–mass spectrometry to analyze 94 breath samples from the 11 participants, starting at a median fasting plasma glucose level of 150 mg/dL all the way down to 50 mg/dL, and back up to recovery. Samples collected at the 90-mg/dL and 80-mg/dL levels demonstrated VOC concentrations very similar to those at and below the hypoglycemia threshold of 70 mg/dL.
Even at 90 mg/dL, the VOC profile “looked like patients were already low. These volatile compounds change early” and stay on the breath as plasma glucose drops. “They are different from normal levels for the entire time, and separate out nicely,” Dr. Siegel said.
The team is not saying which volatile compounds are involved while the sensor is under development. They are looking for funding, and if all goes well, they hope to submit a device application to the Food and Drug Administration in 2020.
Other teams are also looking to VOCs to replace poor Fido, but he can alert to hyperglycemia and other problems as well, so his job is safe for now.
The work has been supported by the National Science Foundation. Dr. Siegel did not have any disclosures.
SOURCE: Siegel AP et al. ADA 2019, Abstract 968-P.
REPORTING FROM ADA 2019