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FDA approves first-ever agent to delay type 1 diabetes onset
“Today’s approval of a first-in-class therapy adds an important new treatment option for certain at-risk patients,” said John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research. “The drug’s potential to delay clinical diagnosis of type 1 diabetes may provide patients with months to years without the burdens of disease.”
The agent, which interferes with T-cell-mediated autoimmune destruction of pancreatic beta cells, is the first disease-modifying therapy for impeding progression of type 1 diabetes. It is administered by intravenous infusion once daily for 14 consecutive days.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In type 1 diabetes staging, adopted in 2015, stage 1 is defined as the presence of beta cell autoimmunity with two or more islet autoantibodies with normoglycemia, stage 2 is beta-cell autoimmunity with dysglycemia yet asymptomatic, and stage 3 is the onset of symptomatic type 1 diabetes.
Stage 2 type 1 diabetes is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
The FDA had previously rejected teplizumab for this indication in July 2021, despite a prior endorsement from an advisory panel in May 2021.
Now, with the FDA approval, Provention Bio cofounder and CEO Ashleigh Palmer said in a statement, “This is a historic occasion for the T1D community and a paradigm shifting breakthrough ... It cannot be emphasized enough how precious a delay in the onset of stage 3 T1D can be from a patient and family perspective; more time to live without and, when necessary, prepare for the burdens, complications, and risks associated with stage 3 disease.”
T1D onset delayed by 2 years
In 2019, a pivotal phase 2, randomized, placebo-controlled trial involving 76 at-risk children and adults aged 8 years and older showed that a single 14-day treatment of daily intravenous infusions of teplizumab in 44 patients resulted in a significant median 2-year delay to onset of clinical type 1 diabetes compared with 32 who received placebo.
Those “game changer” data were presented at the American Diabetes Association (ADA) annual meeting in June 2019 and simultaneously published in the New England Journal of Medicine.
Three-year data were presented at the June 2020 ADA meeting and published in March 2021 in Science Translational Medicine, by Emily K. Sims, MD, department of pediatrics, Indiana University, Indianapolis, and colleagues.
At a median follow-up of 923 days, 50% of those randomly assigned to teplizumab remained diabetes free, compared with 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01). The teplizumab group had a greater average C-peptide area under the curve compared with placebo, reflecting improved beta-cell function (1.96 vs. 1.68 pmol/mL; P = .006).
C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).
“The mid-range time from randomization to stage 3 type 1 diabetes diagnosis was 50 months for the patients who received Tzield and 25 months for those who received a placebo. This represents a statistically significant delay in the development of stage 3 type 1 diabetes,” according to the FDA statement.
The most common side effects of Tzield include lymphopenia (73% teplizumab vs. 6% placebo), rash (36% vs. 0%), leukopenia (221% vs. 0%), and headache (11% vs. 6%). Label warnings and precautions include monitoring for cytokine release syndrome, risk for serious infections, and avoidance of live, inactivated, and mRNA vaccines.
This approval is likely to accelerate discussion about universal autoantibody screening. Currently, most individuals identified as having preclinical type 1 diabetes are first-degree relatives of people with type 1 diabetes identified through the federally funded TrialNet program. In December 2020, the type 1 diabetes research and advocacy organization JDRF began offering a $55 home blood test to screen for the antibodies, and other screening programs have been launched in the United States and Europe.
Previous studies have examined cost-effectiveness of universal screening in children and the optimal ages that such screening should take place.
In October, Provention Bio announced a co-promotion agreement with Sanofi for the U.S. launch of Tzield for delay in onset of clinical T1D in at-risk individuals. Provention Bio offers financial assistance options (e.g., copay assistance) to eligible patients for out-of-pocket costs.
A version of this article first appeared on Medscape.com.
“Today’s approval of a first-in-class therapy adds an important new treatment option for certain at-risk patients,” said John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research. “The drug’s potential to delay clinical diagnosis of type 1 diabetes may provide patients with months to years without the burdens of disease.”
The agent, which interferes with T-cell-mediated autoimmune destruction of pancreatic beta cells, is the first disease-modifying therapy for impeding progression of type 1 diabetes. It is administered by intravenous infusion once daily for 14 consecutive days.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In type 1 diabetes staging, adopted in 2015, stage 1 is defined as the presence of beta cell autoimmunity with two or more islet autoantibodies with normoglycemia, stage 2 is beta-cell autoimmunity with dysglycemia yet asymptomatic, and stage 3 is the onset of symptomatic type 1 diabetes.
Stage 2 type 1 diabetes is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
The FDA had previously rejected teplizumab for this indication in July 2021, despite a prior endorsement from an advisory panel in May 2021.
Now, with the FDA approval, Provention Bio cofounder and CEO Ashleigh Palmer said in a statement, “This is a historic occasion for the T1D community and a paradigm shifting breakthrough ... It cannot be emphasized enough how precious a delay in the onset of stage 3 T1D can be from a patient and family perspective; more time to live without and, when necessary, prepare for the burdens, complications, and risks associated with stage 3 disease.”
T1D onset delayed by 2 years
In 2019, a pivotal phase 2, randomized, placebo-controlled trial involving 76 at-risk children and adults aged 8 years and older showed that a single 14-day treatment of daily intravenous infusions of teplizumab in 44 patients resulted in a significant median 2-year delay to onset of clinical type 1 diabetes compared with 32 who received placebo.
Those “game changer” data were presented at the American Diabetes Association (ADA) annual meeting in June 2019 and simultaneously published in the New England Journal of Medicine.
Three-year data were presented at the June 2020 ADA meeting and published in March 2021 in Science Translational Medicine, by Emily K. Sims, MD, department of pediatrics, Indiana University, Indianapolis, and colleagues.
At a median follow-up of 923 days, 50% of those randomly assigned to teplizumab remained diabetes free, compared with 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01). The teplizumab group had a greater average C-peptide area under the curve compared with placebo, reflecting improved beta-cell function (1.96 vs. 1.68 pmol/mL; P = .006).
C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).
“The mid-range time from randomization to stage 3 type 1 diabetes diagnosis was 50 months for the patients who received Tzield and 25 months for those who received a placebo. This represents a statistically significant delay in the development of stage 3 type 1 diabetes,” according to the FDA statement.
The most common side effects of Tzield include lymphopenia (73% teplizumab vs. 6% placebo), rash (36% vs. 0%), leukopenia (221% vs. 0%), and headache (11% vs. 6%). Label warnings and precautions include monitoring for cytokine release syndrome, risk for serious infections, and avoidance of live, inactivated, and mRNA vaccines.
This approval is likely to accelerate discussion about universal autoantibody screening. Currently, most individuals identified as having preclinical type 1 diabetes are first-degree relatives of people with type 1 diabetes identified through the federally funded TrialNet program. In December 2020, the type 1 diabetes research and advocacy organization JDRF began offering a $55 home blood test to screen for the antibodies, and other screening programs have been launched in the United States and Europe.
Previous studies have examined cost-effectiveness of universal screening in children and the optimal ages that such screening should take place.
In October, Provention Bio announced a co-promotion agreement with Sanofi for the U.S. launch of Tzield for delay in onset of clinical T1D in at-risk individuals. Provention Bio offers financial assistance options (e.g., copay assistance) to eligible patients for out-of-pocket costs.
A version of this article first appeared on Medscape.com.
“Today’s approval of a first-in-class therapy adds an important new treatment option for certain at-risk patients,” said John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research. “The drug’s potential to delay clinical diagnosis of type 1 diabetes may provide patients with months to years without the burdens of disease.”
The agent, which interferes with T-cell-mediated autoimmune destruction of pancreatic beta cells, is the first disease-modifying therapy for impeding progression of type 1 diabetes. It is administered by intravenous infusion once daily for 14 consecutive days.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In type 1 diabetes staging, adopted in 2015, stage 1 is defined as the presence of beta cell autoimmunity with two or more islet autoantibodies with normoglycemia, stage 2 is beta-cell autoimmunity with dysglycemia yet asymptomatic, and stage 3 is the onset of symptomatic type 1 diabetes.
Stage 2 type 1 diabetes is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
The FDA had previously rejected teplizumab for this indication in July 2021, despite a prior endorsement from an advisory panel in May 2021.
Now, with the FDA approval, Provention Bio cofounder and CEO Ashleigh Palmer said in a statement, “This is a historic occasion for the T1D community and a paradigm shifting breakthrough ... It cannot be emphasized enough how precious a delay in the onset of stage 3 T1D can be from a patient and family perspective; more time to live without and, when necessary, prepare for the burdens, complications, and risks associated with stage 3 disease.”
T1D onset delayed by 2 years
In 2019, a pivotal phase 2, randomized, placebo-controlled trial involving 76 at-risk children and adults aged 8 years and older showed that a single 14-day treatment of daily intravenous infusions of teplizumab in 44 patients resulted in a significant median 2-year delay to onset of clinical type 1 diabetes compared with 32 who received placebo.
Those “game changer” data were presented at the American Diabetes Association (ADA) annual meeting in June 2019 and simultaneously published in the New England Journal of Medicine.
Three-year data were presented at the June 2020 ADA meeting and published in March 2021 in Science Translational Medicine, by Emily K. Sims, MD, department of pediatrics, Indiana University, Indianapolis, and colleagues.
At a median follow-up of 923 days, 50% of those randomly assigned to teplizumab remained diabetes free, compared with 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01). The teplizumab group had a greater average C-peptide area under the curve compared with placebo, reflecting improved beta-cell function (1.96 vs. 1.68 pmol/mL; P = .006).
C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).
“The mid-range time from randomization to stage 3 type 1 diabetes diagnosis was 50 months for the patients who received Tzield and 25 months for those who received a placebo. This represents a statistically significant delay in the development of stage 3 type 1 diabetes,” according to the FDA statement.
The most common side effects of Tzield include lymphopenia (73% teplizumab vs. 6% placebo), rash (36% vs. 0%), leukopenia (221% vs. 0%), and headache (11% vs. 6%). Label warnings and precautions include monitoring for cytokine release syndrome, risk for serious infections, and avoidance of live, inactivated, and mRNA vaccines.
This approval is likely to accelerate discussion about universal autoantibody screening. Currently, most individuals identified as having preclinical type 1 diabetes are first-degree relatives of people with type 1 diabetes identified through the federally funded TrialNet program. In December 2020, the type 1 diabetes research and advocacy organization JDRF began offering a $55 home blood test to screen for the antibodies, and other screening programs have been launched in the United States and Europe.
Previous studies have examined cost-effectiveness of universal screening in children and the optimal ages that such screening should take place.
In October, Provention Bio announced a co-promotion agreement with Sanofi for the U.S. launch of Tzield for delay in onset of clinical T1D in at-risk individuals. Provention Bio offers financial assistance options (e.g., copay assistance) to eligible patients for out-of-pocket costs.
A version of this article first appeared on Medscape.com.
Has the time come for glucose monitors for people without diabetes?
Use of continuous glucose monitoring (CGM) by people without diabetes is becoming increasingly popular despite little evidence of benefit thus far, prompting discussion in the diabetes technology community about best practices.
Emerging uses for CGM outside of diabetes include improving glucose patterns to avoid diabetes, improving mental or physical performance, and promoting motivation for healthy behavior change. Such uses are not approved by the Food and Drug Administration and not covered by health insurance, yet a growing number of people are paying digital health companies for the devices as part of wellness packages.
In a related issue that highlights a limitation in this area, new data suggest that the “glucose management indicator (GMI)” feature of CGMs used for diabetes management – a percentage derived from people with diabetes and elevated A1c – may overestimate the actual A1c level in people without diabetes or those with diabetes who maintain A1c less than 6.5%.
“This is an evolving space ... CGM in people with prediabetes may be beneficial, but we need more data and evidence to recommend it. CGM metrics such as time-in-range and GMI are designed for people with type 1 and type 2 diabetes, and therefore, they are not applicable for people without diabetes,” Viral Shah, MD, said in an interview.
During the recent virtual Diabetes Technology Society meeting, Dr. Shah presented results from a soon-to-be published study finding that on average, GMI was 0.59% higher in people with A1c less than 5.7% and 0.49% higher for A1c 5.7%-6.4%, both significant (P < .0001). Dr. Shah, of the Barbara Davis Center for Diabetes, Adult Clinic, Aurora, Colorado, also presented those data in June at the annual scientific sessions of the American Diabetes Association.
Juan Espinoza, MD, of Children’s Hospital Los Angeles, told this news organization that there are data showing that CGM can be a “powerful biofeedback tool” in people with obesity who don’t have diabetes. “Since they don’t have diabetes the time in range or GMI is meaningless. What’s useful for them is seeing the glucose changes in real time and then using that as a trigger for behavioral change.”
‘An idea whose time has come?’
Dr. Espinoza was a co-author on a review published online in the Journal of Diabetes Science and Technology, entitled, “Use of Continuous Glucose Monitors by People Without Diabetes: An Idea Whose Time Has Come?”
The review examines several aspects of the issue, beginning with studies that used CGM to investigate glucose concentrations in people with normal fasting glucose and glucose tolerance tests. Nearly all those individuals – from populations around the world – fell in the blood glucose range of 70-140 mg/dL.
Also reviewed are studies using CGM to study effects of diet, exercise, and stress on glucose levels in people without diabetes. Subsequent sections summarize the limited data that are available suggesting potential benefit for use of CGM in metabolic disease including prediabetes and obesity, non-metabolic conditions such as steroid treatment or parenteral nutrition, health and wellness, and among elite athletes. In that last group, glucose levels in both the hypoglycemic and hyperglycemic ranges during intensive activity have been documented.
Currently, there are four CGM devices that are FDA-approved for use in people with diabetes: FreeStyle Libre (Abbott), the implantable Eversense (Senseonics), and devices from Dexcom and Medtronic.
As Dr. Espinoza and colleagues explain in their review, most of the commercial health and wellness CGM programs, such as Nutrisense, Signos, and Supersapiens, actually use sensors made by those same manufacturers. Nutrisense and Supersapiens use the Libre, and Signos uses the Dexcom.
But, rather than the manufacturer’s apps meant for use by people with diabetes, the wellness companies pair the sensors with their own specially designed apps and typically offer additional services such as health coaching or nutrition counseling “to improve general health.”
Subscribers pay a monthly fee. Signos, for example, charges $399 for 1 month, $199/month for 3 months, or $159/month for 6 months. A prescription is required, but the company’s website says, “rest assured, an independent physician will handle the prescription for you, so you won’t need to arrange for a doctor visit. It is included in the cost of membership.”
Several consumer health product companies are now developing non-invasive glucose monitors, most often as a wristwatch, for people without diabetes to measure glucose optically from the skin in the wrist.
“It remains to be determined how accurate these new devices will be and how they will be regulated,” the researchers write.
What to do with the data?
The dedicated health and wellness apps typically provide average glucose and trend data but not the GMI. However, in theory users could access that metric by downloading the manufacturers’ viewing apps – for example, Clarity for Dexcom or LibreView for Libre.
Moreover, a person without diabetes could always obtain an off-label prescription from their physician for a FreeStyle Libre and purchase it at a pharmacy. At Walmart, for example, the cost for two boxes of two glucose meters with 14 days of wear each is $136.77. In that situation as well, users could download the viewing app that contains the summary data including the GMI that could potentially mislead in the setting of consistent normoglycemia.
Dr. Espinoza said: “I think there’s certainly value in glucose levels. We know the summary metrics are useful in type 1 diabetes. We don’t know which summary metrics are going to be useful in any other disease states. We may need brand new summary metrics for other disease states where it’s not about time in range. Maybe the thing that matters is the frequency or height of spikes. We don’t have a measure for that.”
He added that despite the availability of normative data, “even people without diabetes are a fairly heterogenous group. They can still have insulin resistance, so it’s tricky. From a science standpoint, we probably need studies with hundreds of patients with well-established A1c and [insulin resistance measures], weight, and body mass index. Then and only then will we be able to give an accurate glucose profile.”
In the meantime, “more data is always a good thing, but the hard thing is figuring out what do we do with it. Maybe it’s biofeedback for behavioral modification. We don’t know yet. But these are powerful tools and maybe we should learn how to use them better.”
Dr. Shah has reported receiving research grants and participating in advisory boards for Dexcom and Sanofi US. Dr. Espinoza has reported receiving research funding from the National Institutes of Health and FDA.
A version of this article first appeared on Medscape.com.
Use of continuous glucose monitoring (CGM) by people without diabetes is becoming increasingly popular despite little evidence of benefit thus far, prompting discussion in the diabetes technology community about best practices.
Emerging uses for CGM outside of diabetes include improving glucose patterns to avoid diabetes, improving mental or physical performance, and promoting motivation for healthy behavior change. Such uses are not approved by the Food and Drug Administration and not covered by health insurance, yet a growing number of people are paying digital health companies for the devices as part of wellness packages.
In a related issue that highlights a limitation in this area, new data suggest that the “glucose management indicator (GMI)” feature of CGMs used for diabetes management – a percentage derived from people with diabetes and elevated A1c – may overestimate the actual A1c level in people without diabetes or those with diabetes who maintain A1c less than 6.5%.
“This is an evolving space ... CGM in people with prediabetes may be beneficial, but we need more data and evidence to recommend it. CGM metrics such as time-in-range and GMI are designed for people with type 1 and type 2 diabetes, and therefore, they are not applicable for people without diabetes,” Viral Shah, MD, said in an interview.
During the recent virtual Diabetes Technology Society meeting, Dr. Shah presented results from a soon-to-be published study finding that on average, GMI was 0.59% higher in people with A1c less than 5.7% and 0.49% higher for A1c 5.7%-6.4%, both significant (P < .0001). Dr. Shah, of the Barbara Davis Center for Diabetes, Adult Clinic, Aurora, Colorado, also presented those data in June at the annual scientific sessions of the American Diabetes Association.
Juan Espinoza, MD, of Children’s Hospital Los Angeles, told this news organization that there are data showing that CGM can be a “powerful biofeedback tool” in people with obesity who don’t have diabetes. “Since they don’t have diabetes the time in range or GMI is meaningless. What’s useful for them is seeing the glucose changes in real time and then using that as a trigger for behavioral change.”
‘An idea whose time has come?’
Dr. Espinoza was a co-author on a review published online in the Journal of Diabetes Science and Technology, entitled, “Use of Continuous Glucose Monitors by People Without Diabetes: An Idea Whose Time Has Come?”
The review examines several aspects of the issue, beginning with studies that used CGM to investigate glucose concentrations in people with normal fasting glucose and glucose tolerance tests. Nearly all those individuals – from populations around the world – fell in the blood glucose range of 70-140 mg/dL.
Also reviewed are studies using CGM to study effects of diet, exercise, and stress on glucose levels in people without diabetes. Subsequent sections summarize the limited data that are available suggesting potential benefit for use of CGM in metabolic disease including prediabetes and obesity, non-metabolic conditions such as steroid treatment or parenteral nutrition, health and wellness, and among elite athletes. In that last group, glucose levels in both the hypoglycemic and hyperglycemic ranges during intensive activity have been documented.
Currently, there are four CGM devices that are FDA-approved for use in people with diabetes: FreeStyle Libre (Abbott), the implantable Eversense (Senseonics), and devices from Dexcom and Medtronic.
As Dr. Espinoza and colleagues explain in their review, most of the commercial health and wellness CGM programs, such as Nutrisense, Signos, and Supersapiens, actually use sensors made by those same manufacturers. Nutrisense and Supersapiens use the Libre, and Signos uses the Dexcom.
But, rather than the manufacturer’s apps meant for use by people with diabetes, the wellness companies pair the sensors with their own specially designed apps and typically offer additional services such as health coaching or nutrition counseling “to improve general health.”
Subscribers pay a monthly fee. Signos, for example, charges $399 for 1 month, $199/month for 3 months, or $159/month for 6 months. A prescription is required, but the company’s website says, “rest assured, an independent physician will handle the prescription for you, so you won’t need to arrange for a doctor visit. It is included in the cost of membership.”
Several consumer health product companies are now developing non-invasive glucose monitors, most often as a wristwatch, for people without diabetes to measure glucose optically from the skin in the wrist.
“It remains to be determined how accurate these new devices will be and how they will be regulated,” the researchers write.
What to do with the data?
The dedicated health and wellness apps typically provide average glucose and trend data but not the GMI. However, in theory users could access that metric by downloading the manufacturers’ viewing apps – for example, Clarity for Dexcom or LibreView for Libre.
Moreover, a person without diabetes could always obtain an off-label prescription from their physician for a FreeStyle Libre and purchase it at a pharmacy. At Walmart, for example, the cost for two boxes of two glucose meters with 14 days of wear each is $136.77. In that situation as well, users could download the viewing app that contains the summary data including the GMI that could potentially mislead in the setting of consistent normoglycemia.
Dr. Espinoza said: “I think there’s certainly value in glucose levels. We know the summary metrics are useful in type 1 diabetes. We don’t know which summary metrics are going to be useful in any other disease states. We may need brand new summary metrics for other disease states where it’s not about time in range. Maybe the thing that matters is the frequency or height of spikes. We don’t have a measure for that.”
He added that despite the availability of normative data, “even people without diabetes are a fairly heterogenous group. They can still have insulin resistance, so it’s tricky. From a science standpoint, we probably need studies with hundreds of patients with well-established A1c and [insulin resistance measures], weight, and body mass index. Then and only then will we be able to give an accurate glucose profile.”
In the meantime, “more data is always a good thing, but the hard thing is figuring out what do we do with it. Maybe it’s biofeedback for behavioral modification. We don’t know yet. But these are powerful tools and maybe we should learn how to use them better.”
Dr. Shah has reported receiving research grants and participating in advisory boards for Dexcom and Sanofi US. Dr. Espinoza has reported receiving research funding from the National Institutes of Health and FDA.
A version of this article first appeared on Medscape.com.
Use of continuous glucose monitoring (CGM) by people without diabetes is becoming increasingly popular despite little evidence of benefit thus far, prompting discussion in the diabetes technology community about best practices.
Emerging uses for CGM outside of diabetes include improving glucose patterns to avoid diabetes, improving mental or physical performance, and promoting motivation for healthy behavior change. Such uses are not approved by the Food and Drug Administration and not covered by health insurance, yet a growing number of people are paying digital health companies for the devices as part of wellness packages.
In a related issue that highlights a limitation in this area, new data suggest that the “glucose management indicator (GMI)” feature of CGMs used for diabetes management – a percentage derived from people with diabetes and elevated A1c – may overestimate the actual A1c level in people without diabetes or those with diabetes who maintain A1c less than 6.5%.
“This is an evolving space ... CGM in people with prediabetes may be beneficial, but we need more data and evidence to recommend it. CGM metrics such as time-in-range and GMI are designed for people with type 1 and type 2 diabetes, and therefore, they are not applicable for people without diabetes,” Viral Shah, MD, said in an interview.
During the recent virtual Diabetes Technology Society meeting, Dr. Shah presented results from a soon-to-be published study finding that on average, GMI was 0.59% higher in people with A1c less than 5.7% and 0.49% higher for A1c 5.7%-6.4%, both significant (P < .0001). Dr. Shah, of the Barbara Davis Center for Diabetes, Adult Clinic, Aurora, Colorado, also presented those data in June at the annual scientific sessions of the American Diabetes Association.
Juan Espinoza, MD, of Children’s Hospital Los Angeles, told this news organization that there are data showing that CGM can be a “powerful biofeedback tool” in people with obesity who don’t have diabetes. “Since they don’t have diabetes the time in range or GMI is meaningless. What’s useful for them is seeing the glucose changes in real time and then using that as a trigger for behavioral change.”
‘An idea whose time has come?’
Dr. Espinoza was a co-author on a review published online in the Journal of Diabetes Science and Technology, entitled, “Use of Continuous Glucose Monitors by People Without Diabetes: An Idea Whose Time Has Come?”
The review examines several aspects of the issue, beginning with studies that used CGM to investigate glucose concentrations in people with normal fasting glucose and glucose tolerance tests. Nearly all those individuals – from populations around the world – fell in the blood glucose range of 70-140 mg/dL.
Also reviewed are studies using CGM to study effects of diet, exercise, and stress on glucose levels in people without diabetes. Subsequent sections summarize the limited data that are available suggesting potential benefit for use of CGM in metabolic disease including prediabetes and obesity, non-metabolic conditions such as steroid treatment or parenteral nutrition, health and wellness, and among elite athletes. In that last group, glucose levels in both the hypoglycemic and hyperglycemic ranges during intensive activity have been documented.
Currently, there are four CGM devices that are FDA-approved for use in people with diabetes: FreeStyle Libre (Abbott), the implantable Eversense (Senseonics), and devices from Dexcom and Medtronic.
As Dr. Espinoza and colleagues explain in their review, most of the commercial health and wellness CGM programs, such as Nutrisense, Signos, and Supersapiens, actually use sensors made by those same manufacturers. Nutrisense and Supersapiens use the Libre, and Signos uses the Dexcom.
But, rather than the manufacturer’s apps meant for use by people with diabetes, the wellness companies pair the sensors with their own specially designed apps and typically offer additional services such as health coaching or nutrition counseling “to improve general health.”
Subscribers pay a monthly fee. Signos, for example, charges $399 for 1 month, $199/month for 3 months, or $159/month for 6 months. A prescription is required, but the company’s website says, “rest assured, an independent physician will handle the prescription for you, so you won’t need to arrange for a doctor visit. It is included in the cost of membership.”
Several consumer health product companies are now developing non-invasive glucose monitors, most often as a wristwatch, for people without diabetes to measure glucose optically from the skin in the wrist.
“It remains to be determined how accurate these new devices will be and how they will be regulated,” the researchers write.
What to do with the data?
The dedicated health and wellness apps typically provide average glucose and trend data but not the GMI. However, in theory users could access that metric by downloading the manufacturers’ viewing apps – for example, Clarity for Dexcom or LibreView for Libre.
Moreover, a person without diabetes could always obtain an off-label prescription from their physician for a FreeStyle Libre and purchase it at a pharmacy. At Walmart, for example, the cost for two boxes of two glucose meters with 14 days of wear each is $136.77. In that situation as well, users could download the viewing app that contains the summary data including the GMI that could potentially mislead in the setting of consistent normoglycemia.
Dr. Espinoza said: “I think there’s certainly value in glucose levels. We know the summary metrics are useful in type 1 diabetes. We don’t know which summary metrics are going to be useful in any other disease states. We may need brand new summary metrics for other disease states where it’s not about time in range. Maybe the thing that matters is the frequency or height of spikes. We don’t have a measure for that.”
He added that despite the availability of normative data, “even people without diabetes are a fairly heterogenous group. They can still have insulin resistance, so it’s tricky. From a science standpoint, we probably need studies with hundreds of patients with well-established A1c and [insulin resistance measures], weight, and body mass index. Then and only then will we be able to give an accurate glucose profile.”
In the meantime, “more data is always a good thing, but the hard thing is figuring out what do we do with it. Maybe it’s biofeedback for behavioral modification. We don’t know yet. But these are powerful tools and maybe we should learn how to use them better.”
Dr. Shah has reported receiving research grants and participating in advisory boards for Dexcom and Sanofi US. Dr. Espinoza has reported receiving research funding from the National Institutes of Health and FDA.
A version of this article first appeared on Medscape.com.
AT ADA 2022
Exercise later in the day for better blood glucose control?
The data come from 775 participants with a mean body mass index (BMI) of 26.2 kg/m2 in the observational Netherlands Epidemiology of Obesity (NEO) study. Use of activity monitors for four consecutive days showed that performance of MVPA (defined as activity with intensity of > 3 metabolic equivalents of task) in the afternoon or evening was associated with up to 25% reduced insulin resistance compared with an even distribution of activity during the day.
“This is one of the first studies where in humans the relation between timing of physical activity and insulin resistance was examined,” lead author Jeroen van der Velde of the department of clinical epidemiology, Leiden (the Netherlands) University Medical Center, said in an interview.
Moreover, he noted that, while previous intervention studies have shown greater blood glucose reduction with high-intensity exercise performed in the afternoon, compared with the morning, in people with impaired glucose metabolism or type 2 diabetes, “as far as I am aware, we were the first to use a population-based study in a general population to study this.”
Katarina Kos, MD, PhD, senior lecturer in diabetes and obesity, University of Exeter (England), said: “This study is novel in that it relates the timing of physical activity if performed in the morning, afternoon, or evening to insulin resistance and fat content. This is from a cohort of middle-aged Dutch people between ages 45-65 studied 10 years ago and based on self-reports of weight and eating behavior and who were found to be generally overweight.”
Is it down to circadian rhythm?
“The results are of interest in that if the chosen timing was in the afternoon [63% of studied population] or evening (8% of the studied population), it seemed to relate with improved metabolism when compared to the morning exercising [16% of population]. ... Whether this was due to the (timing) of activity is yet to be shown,” Dr. Kos told the UK Science Media Centre.
Mr. van der Velde agrees that the effect may be explained at least in part by the circadian rhythm of the body. “Physical activity may act as ... a cue for the activation of clock genes. Previous research has suggested that our body’s muscular system and oxidative system are also affected by our circadian rhythm and their peak activity seems to be in the late afternoon. So, being mostly active in this time period ... may elicit greater metabolic responses compared to being active in the morning.”
But, he cautioned, “I think it is important to realize that we are just beginning to understand the potential impact of physical activity timing. At this stage, I believe it is most important to be physically active in general. So ... if the morning is the only time of the day to go for a walk or a run, certainly do this.”
Dr. Kos concurred: “As this is not an intervention study, further research is needed to explain the cause of the observed association.”
Mr. van der Velde also added that it’s not yet clear which individuals or subgroups might experience additional benefits from timed activities. That’s the current research focus of a large consortium of several research institutes in the Netherlands and Canada.
Timed exercise reduces insulin resistance but not liver fat
The findings were published online in Diabetologia.
The study population included men and women living in the greater Leiden area in the western Netherlands who were aged 45-65 years and self-reported a BMI of 27 or higher. A second cohort included inhabitants of one municipality who were invited to participate regardless of their BMI. All wore the activity monitors for 4 consecutive days and nights during their usual activities.
Neither sedentary time nor breaks in sedentary time (defined as a period of activity with an acceleration greater than 0.75 m/s2 following a sedentary period) were associated with lower insulin resistance, as calculated by blood sampling.
However, the number of breaks in sedentary time was associated with a significant 22% higher liver fat content, assessed with proton magnetic resonance spectroscopy.
One reason for the lack of effect of breaks on insulin resistance, the authors theorized, is that this was a real-world observational study where regular breaks aren’t common. Alternatively, people might not have been intensively active enough during breaks to make a difference.
After adjustment for total body fat, an additional hour of MVPA was associated with a 5% drop in insulin resistance. An additional hour of MVPA in 5-minute bouts was associated with 9% lower insulin resistance.
Also after adjustments, insulin resistance was reduced significantly in participants who were most active in the afternoon, by 18%, or evening, by 25%, whereas insulin resistance was not affected among those who were most active in the morning (–3%), all compared with people who distributed their MVPA throughout the day.
Timing of MVPA was not associated with liver fat content, and there were no significant differences in liver fat content and insulin resistance between groups based on timing of light physical activity.
“This is just speculation, but perhaps for fat accumulation in the liver the circadian system is less involved. Or perhaps timing of other lifestyle variables are more important here, such as dietary intake,” Mr. van der Velde said.
Finally, he observed, “timing of physical activity is most likely just a piece of the puzzle. Timing of other lifestyle behavior, such as sleep, and food intake are important cues for our circadian system as well, and it is likely that all these behaviors interact with each other.”
The NEO study is supported by Leiden University Medical Center, the Netherlands Cardiovascular Research Initiative, an initiative supported by the Dutch Heart Foundation, and the Netherlands Organisation for Health Research and Development/Partnership Diabetes/Dutch Diabetes foundation Breakthrough. Mr. van der Velde has reported no further disclosures.
A version of this article first appeared on Medscape.com.
The data come from 775 participants with a mean body mass index (BMI) of 26.2 kg/m2 in the observational Netherlands Epidemiology of Obesity (NEO) study. Use of activity monitors for four consecutive days showed that performance of MVPA (defined as activity with intensity of > 3 metabolic equivalents of task) in the afternoon or evening was associated with up to 25% reduced insulin resistance compared with an even distribution of activity during the day.
“This is one of the first studies where in humans the relation between timing of physical activity and insulin resistance was examined,” lead author Jeroen van der Velde of the department of clinical epidemiology, Leiden (the Netherlands) University Medical Center, said in an interview.
Moreover, he noted that, while previous intervention studies have shown greater blood glucose reduction with high-intensity exercise performed in the afternoon, compared with the morning, in people with impaired glucose metabolism or type 2 diabetes, “as far as I am aware, we were the first to use a population-based study in a general population to study this.”
Katarina Kos, MD, PhD, senior lecturer in diabetes and obesity, University of Exeter (England), said: “This study is novel in that it relates the timing of physical activity if performed in the morning, afternoon, or evening to insulin resistance and fat content. This is from a cohort of middle-aged Dutch people between ages 45-65 studied 10 years ago and based on self-reports of weight and eating behavior and who were found to be generally overweight.”
Is it down to circadian rhythm?
“The results are of interest in that if the chosen timing was in the afternoon [63% of studied population] or evening (8% of the studied population), it seemed to relate with improved metabolism when compared to the morning exercising [16% of population]. ... Whether this was due to the (timing) of activity is yet to be shown,” Dr. Kos told the UK Science Media Centre.
Mr. van der Velde agrees that the effect may be explained at least in part by the circadian rhythm of the body. “Physical activity may act as ... a cue for the activation of clock genes. Previous research has suggested that our body’s muscular system and oxidative system are also affected by our circadian rhythm and their peak activity seems to be in the late afternoon. So, being mostly active in this time period ... may elicit greater metabolic responses compared to being active in the morning.”
But, he cautioned, “I think it is important to realize that we are just beginning to understand the potential impact of physical activity timing. At this stage, I believe it is most important to be physically active in general. So ... if the morning is the only time of the day to go for a walk or a run, certainly do this.”
Dr. Kos concurred: “As this is not an intervention study, further research is needed to explain the cause of the observed association.”
Mr. van der Velde also added that it’s not yet clear which individuals or subgroups might experience additional benefits from timed activities. That’s the current research focus of a large consortium of several research institutes in the Netherlands and Canada.
Timed exercise reduces insulin resistance but not liver fat
The findings were published online in Diabetologia.
The study population included men and women living in the greater Leiden area in the western Netherlands who were aged 45-65 years and self-reported a BMI of 27 or higher. A second cohort included inhabitants of one municipality who were invited to participate regardless of their BMI. All wore the activity monitors for 4 consecutive days and nights during their usual activities.
Neither sedentary time nor breaks in sedentary time (defined as a period of activity with an acceleration greater than 0.75 m/s2 following a sedentary period) were associated with lower insulin resistance, as calculated by blood sampling.
However, the number of breaks in sedentary time was associated with a significant 22% higher liver fat content, assessed with proton magnetic resonance spectroscopy.
One reason for the lack of effect of breaks on insulin resistance, the authors theorized, is that this was a real-world observational study where regular breaks aren’t common. Alternatively, people might not have been intensively active enough during breaks to make a difference.
After adjustment for total body fat, an additional hour of MVPA was associated with a 5% drop in insulin resistance. An additional hour of MVPA in 5-minute bouts was associated with 9% lower insulin resistance.
Also after adjustments, insulin resistance was reduced significantly in participants who were most active in the afternoon, by 18%, or evening, by 25%, whereas insulin resistance was not affected among those who were most active in the morning (–3%), all compared with people who distributed their MVPA throughout the day.
Timing of MVPA was not associated with liver fat content, and there were no significant differences in liver fat content and insulin resistance between groups based on timing of light physical activity.
“This is just speculation, but perhaps for fat accumulation in the liver the circadian system is less involved. Or perhaps timing of other lifestyle variables are more important here, such as dietary intake,” Mr. van der Velde said.
Finally, he observed, “timing of physical activity is most likely just a piece of the puzzle. Timing of other lifestyle behavior, such as sleep, and food intake are important cues for our circadian system as well, and it is likely that all these behaviors interact with each other.”
The NEO study is supported by Leiden University Medical Center, the Netherlands Cardiovascular Research Initiative, an initiative supported by the Dutch Heart Foundation, and the Netherlands Organisation for Health Research and Development/Partnership Diabetes/Dutch Diabetes foundation Breakthrough. Mr. van der Velde has reported no further disclosures.
A version of this article first appeared on Medscape.com.
The data come from 775 participants with a mean body mass index (BMI) of 26.2 kg/m2 in the observational Netherlands Epidemiology of Obesity (NEO) study. Use of activity monitors for four consecutive days showed that performance of MVPA (defined as activity with intensity of > 3 metabolic equivalents of task) in the afternoon or evening was associated with up to 25% reduced insulin resistance compared with an even distribution of activity during the day.
“This is one of the first studies where in humans the relation between timing of physical activity and insulin resistance was examined,” lead author Jeroen van der Velde of the department of clinical epidemiology, Leiden (the Netherlands) University Medical Center, said in an interview.
Moreover, he noted that, while previous intervention studies have shown greater blood glucose reduction with high-intensity exercise performed in the afternoon, compared with the morning, in people with impaired glucose metabolism or type 2 diabetes, “as far as I am aware, we were the first to use a population-based study in a general population to study this.”
Katarina Kos, MD, PhD, senior lecturer in diabetes and obesity, University of Exeter (England), said: “This study is novel in that it relates the timing of physical activity if performed in the morning, afternoon, or evening to insulin resistance and fat content. This is from a cohort of middle-aged Dutch people between ages 45-65 studied 10 years ago and based on self-reports of weight and eating behavior and who were found to be generally overweight.”
Is it down to circadian rhythm?
“The results are of interest in that if the chosen timing was in the afternoon [63% of studied population] or evening (8% of the studied population), it seemed to relate with improved metabolism when compared to the morning exercising [16% of population]. ... Whether this was due to the (timing) of activity is yet to be shown,” Dr. Kos told the UK Science Media Centre.
Mr. van der Velde agrees that the effect may be explained at least in part by the circadian rhythm of the body. “Physical activity may act as ... a cue for the activation of clock genes. Previous research has suggested that our body’s muscular system and oxidative system are also affected by our circadian rhythm and their peak activity seems to be in the late afternoon. So, being mostly active in this time period ... may elicit greater metabolic responses compared to being active in the morning.”
But, he cautioned, “I think it is important to realize that we are just beginning to understand the potential impact of physical activity timing. At this stage, I believe it is most important to be physically active in general. So ... if the morning is the only time of the day to go for a walk or a run, certainly do this.”
Dr. Kos concurred: “As this is not an intervention study, further research is needed to explain the cause of the observed association.”
Mr. van der Velde also added that it’s not yet clear which individuals or subgroups might experience additional benefits from timed activities. That’s the current research focus of a large consortium of several research institutes in the Netherlands and Canada.
Timed exercise reduces insulin resistance but not liver fat
The findings were published online in Diabetologia.
The study population included men and women living in the greater Leiden area in the western Netherlands who were aged 45-65 years and self-reported a BMI of 27 or higher. A second cohort included inhabitants of one municipality who were invited to participate regardless of their BMI. All wore the activity monitors for 4 consecutive days and nights during their usual activities.
Neither sedentary time nor breaks in sedentary time (defined as a period of activity with an acceleration greater than 0.75 m/s2 following a sedentary period) were associated with lower insulin resistance, as calculated by blood sampling.
However, the number of breaks in sedentary time was associated with a significant 22% higher liver fat content, assessed with proton magnetic resonance spectroscopy.
One reason for the lack of effect of breaks on insulin resistance, the authors theorized, is that this was a real-world observational study where regular breaks aren’t common. Alternatively, people might not have been intensively active enough during breaks to make a difference.
After adjustment for total body fat, an additional hour of MVPA was associated with a 5% drop in insulin resistance. An additional hour of MVPA in 5-minute bouts was associated with 9% lower insulin resistance.
Also after adjustments, insulin resistance was reduced significantly in participants who were most active in the afternoon, by 18%, or evening, by 25%, whereas insulin resistance was not affected among those who were most active in the morning (–3%), all compared with people who distributed their MVPA throughout the day.
Timing of MVPA was not associated with liver fat content, and there were no significant differences in liver fat content and insulin resistance between groups based on timing of light physical activity.
“This is just speculation, but perhaps for fat accumulation in the liver the circadian system is less involved. Or perhaps timing of other lifestyle variables are more important here, such as dietary intake,” Mr. van der Velde said.
Finally, he observed, “timing of physical activity is most likely just a piece of the puzzle. Timing of other lifestyle behavior, such as sleep, and food intake are important cues for our circadian system as well, and it is likely that all these behaviors interact with each other.”
The NEO study is supported by Leiden University Medical Center, the Netherlands Cardiovascular Research Initiative, an initiative supported by the Dutch Heart Foundation, and the Netherlands Organisation for Health Research and Development/Partnership Diabetes/Dutch Diabetes foundation Breakthrough. Mr. van der Velde has reported no further disclosures.
A version of this article first appeared on Medscape.com.
FROM DIABETOLOGIA
Vitamin D deficiency linked to death, new study finds
Vitamin D deficiency increases mortality risk and raising levels even slightly could decrease the risk, researchers examining data from the UK Biobank have found.
They used a Mendelian randomization approach, which uses genetic variants as “proxy indicators” for external factors that affect vitamin D levels, such as sun exposure or dietary intake. It allows for analysis of the relationship between deficiency and outcomes including mortality, which can’t be done in randomized clinical trials for ethical reasons.
Using this method, nutritionist Joshua P. Sutherland, PhD, of the Australian Centre for Precision Health, Adelaide, and colleagues found an association between genetically predicted vitamin D levels [25-(OH)D] and mortality from several major causes, with evidence of causality among people with measured concentrations below, but not above, 50 nmol/L. The findings were published online in Annals of Internal Medicine.
“Unlike other types of observational studies, we have overcome some of the methodological obstacles. What is special about this new study is we were able to look at people with very low vitamin D concentrations and what would happen if their concentrations were a little bit higher. Most randomized controlled trials don’t show much of an effect. That’s because most people have sufficient concentrations. Ethically you can’t do a trial of people with very low levels without treating them,” senior author Elina Hypp
The data support the 50 nmol/L cut-off endorsed by the United States National Academy of Medicine and align with previous data suggesting the benefit of vitamin D supplementation is largely seen in people with deficiency.
“Everybody with vitamin D levels less than 50 nmol/L is recommended to increase their levels. Our results suggest there’s no need to go very high. The positive message is that if we are able to raise levels to just the current U.S. recommendations, that’s fine. There’s no need to use large supplement doses,” Dr. Hyppönen explained.
Thus, she advised, “Supplementation will clearly help, especially during wintertime or if a person isn’t getting enough vitamin D from the sun or in places where food isn’t fortified with vitamin D.”
But the data don’t support the approach of using large intermittent doses, she added.
“Sometimes doctors want to fix the deficiency quickly with a large ‘bolus’ dose, then continue with a maintenance dose. Increasing evidence suggests that’s not beneficial and might disturb the body’s metabolism so that it can’t get the amount it needs. It’s safe overall but might not work the way we want it to work.”
Rather, Dr. Hyppönen said, “My sense is that daily modest vitamin D dose supplementation when it’s needed is the best way forward.”
Genetic approach reveals causal relationship
The investigators analyzed data from 307,601 individuals in the UK Biobank, a prospective cohort of people recruited from England, Scotland, and Wales during March 2006 and July 2010. Most were of White European ancestry and were aged 37-73 years at baseline.
Genetically predicted vitamin D levels were estimated using 35 confirmed 25-(OH)D variants. Participants were followed for outcomes up to June 2020.
The average baseline measured 25-(OH)D concentration was 45.2 nmol/L, and 11.7% (n = 36,009) of participants had levels between 10.0 and 24.9 nmol/L. Higher levels were seen in people living in southern areas and nonsmokers as well as those with a higher level of physical activity, less socioeconomic deprivation, and lower body mass index.
During follow-up, 6.1% of participants died (n = 18,700). After adjustment for variables, odds ratios for all causes of mortality were highest among people with 25-(OH)D levels below 25 nmol/L and appeared to plateau between 50 and 75 nmol/L, with no further reduction in mortality at values of 75-125 nmol/L.
Mortality 36% higher in those deficient in vitamin D
The risk for mortality was a significant 36% higher for participants with 25-(OH)D 25 nmol/L compared with 50 nmol/L.
With the Mendelian randomization, there was an L-shaped association between genetically predicted 25-(OH)D level and all-cause mortality (P for nonlinearity < .001) and for mortality because of cancer and cardiovascular disease (P for nonlinearity ≤ .033).
Again, the strongest association with those outcomes and genetically predicted 25-(OH)D was found at levels below 25 nmol/L and a plateau was seen by 50 nmol/L.
Compared with a measured 25-(OH)D concentration of 50 nmol/L, investigators estimated that the genetically predicted odds of all-cause mortality would increase sixfold (odds ratio, 6.00) for participants at 10 nmol/L and by 25% (OR, 1.25) for those at 25 nmol/L.
And, compared with a measured 25-(OH)D concentration of 50 nmol/L, those with 10 nmol/L had genetically predicted odds ratios of 5.98 for cardiovascular mortality, 3.37 for cancer mortality, and 12.44 for respiratory mortality.
Comparing measured 25-(OH)D concentrations of 25 nmol/L versus 50 nmol/L, odds ratios for those outcomes were 1.25, 1.16, and 1.96 (95% confidence interval, 1.88-4.67), respectively. All were statistically significant.
Consistent results supportive of a causal effect of genetically predicted 25-(OH)D on all-cause mortality in those with low measured vitamin D concentrations were also found in a sensitivity analysis of 20,837 people of non-White ethnic origin.
The study was funded by the Australian National Health and Medical Research Council. Dr. Sutherland’s studentship is funded by an Australian Research Training Program Scholarship.
A version of this article first appeared on Medscape.com.
Vitamin D deficiency increases mortality risk and raising levels even slightly could decrease the risk, researchers examining data from the UK Biobank have found.
They used a Mendelian randomization approach, which uses genetic variants as “proxy indicators” for external factors that affect vitamin D levels, such as sun exposure or dietary intake. It allows for analysis of the relationship between deficiency and outcomes including mortality, which can’t be done in randomized clinical trials for ethical reasons.
Using this method, nutritionist Joshua P. Sutherland, PhD, of the Australian Centre for Precision Health, Adelaide, and colleagues found an association between genetically predicted vitamin D levels [25-(OH)D] and mortality from several major causes, with evidence of causality among people with measured concentrations below, but not above, 50 nmol/L. The findings were published online in Annals of Internal Medicine.
“Unlike other types of observational studies, we have overcome some of the methodological obstacles. What is special about this new study is we were able to look at people with very low vitamin D concentrations and what would happen if their concentrations were a little bit higher. Most randomized controlled trials don’t show much of an effect. That’s because most people have sufficient concentrations. Ethically you can’t do a trial of people with very low levels without treating them,” senior author Elina Hypp
The data support the 50 nmol/L cut-off endorsed by the United States National Academy of Medicine and align with previous data suggesting the benefit of vitamin D supplementation is largely seen in people with deficiency.
“Everybody with vitamin D levels less than 50 nmol/L is recommended to increase their levels. Our results suggest there’s no need to go very high. The positive message is that if we are able to raise levels to just the current U.S. recommendations, that’s fine. There’s no need to use large supplement doses,” Dr. Hyppönen explained.
Thus, she advised, “Supplementation will clearly help, especially during wintertime or if a person isn’t getting enough vitamin D from the sun or in places where food isn’t fortified with vitamin D.”
But the data don’t support the approach of using large intermittent doses, she added.
“Sometimes doctors want to fix the deficiency quickly with a large ‘bolus’ dose, then continue with a maintenance dose. Increasing evidence suggests that’s not beneficial and might disturb the body’s metabolism so that it can’t get the amount it needs. It’s safe overall but might not work the way we want it to work.”
Rather, Dr. Hyppönen said, “My sense is that daily modest vitamin D dose supplementation when it’s needed is the best way forward.”
Genetic approach reveals causal relationship
The investigators analyzed data from 307,601 individuals in the UK Biobank, a prospective cohort of people recruited from England, Scotland, and Wales during March 2006 and July 2010. Most were of White European ancestry and were aged 37-73 years at baseline.
Genetically predicted vitamin D levels were estimated using 35 confirmed 25-(OH)D variants. Participants were followed for outcomes up to June 2020.
The average baseline measured 25-(OH)D concentration was 45.2 nmol/L, and 11.7% (n = 36,009) of participants had levels between 10.0 and 24.9 nmol/L. Higher levels were seen in people living in southern areas and nonsmokers as well as those with a higher level of physical activity, less socioeconomic deprivation, and lower body mass index.
During follow-up, 6.1% of participants died (n = 18,700). After adjustment for variables, odds ratios for all causes of mortality were highest among people with 25-(OH)D levels below 25 nmol/L and appeared to plateau between 50 and 75 nmol/L, with no further reduction in mortality at values of 75-125 nmol/L.
Mortality 36% higher in those deficient in vitamin D
The risk for mortality was a significant 36% higher for participants with 25-(OH)D 25 nmol/L compared with 50 nmol/L.
With the Mendelian randomization, there was an L-shaped association between genetically predicted 25-(OH)D level and all-cause mortality (P for nonlinearity < .001) and for mortality because of cancer and cardiovascular disease (P for nonlinearity ≤ .033).
Again, the strongest association with those outcomes and genetically predicted 25-(OH)D was found at levels below 25 nmol/L and a plateau was seen by 50 nmol/L.
Compared with a measured 25-(OH)D concentration of 50 nmol/L, investigators estimated that the genetically predicted odds of all-cause mortality would increase sixfold (odds ratio, 6.00) for participants at 10 nmol/L and by 25% (OR, 1.25) for those at 25 nmol/L.
And, compared with a measured 25-(OH)D concentration of 50 nmol/L, those with 10 nmol/L had genetically predicted odds ratios of 5.98 for cardiovascular mortality, 3.37 for cancer mortality, and 12.44 for respiratory mortality.
Comparing measured 25-(OH)D concentrations of 25 nmol/L versus 50 nmol/L, odds ratios for those outcomes were 1.25, 1.16, and 1.96 (95% confidence interval, 1.88-4.67), respectively. All were statistically significant.
Consistent results supportive of a causal effect of genetically predicted 25-(OH)D on all-cause mortality in those with low measured vitamin D concentrations were also found in a sensitivity analysis of 20,837 people of non-White ethnic origin.
The study was funded by the Australian National Health and Medical Research Council. Dr. Sutherland’s studentship is funded by an Australian Research Training Program Scholarship.
A version of this article first appeared on Medscape.com.
Vitamin D deficiency increases mortality risk and raising levels even slightly could decrease the risk, researchers examining data from the UK Biobank have found.
They used a Mendelian randomization approach, which uses genetic variants as “proxy indicators” for external factors that affect vitamin D levels, such as sun exposure or dietary intake. It allows for analysis of the relationship between deficiency and outcomes including mortality, which can’t be done in randomized clinical trials for ethical reasons.
Using this method, nutritionist Joshua P. Sutherland, PhD, of the Australian Centre for Precision Health, Adelaide, and colleagues found an association between genetically predicted vitamin D levels [25-(OH)D] and mortality from several major causes, with evidence of causality among people with measured concentrations below, but not above, 50 nmol/L. The findings were published online in Annals of Internal Medicine.
“Unlike other types of observational studies, we have overcome some of the methodological obstacles. What is special about this new study is we were able to look at people with very low vitamin D concentrations and what would happen if their concentrations were a little bit higher. Most randomized controlled trials don’t show much of an effect. That’s because most people have sufficient concentrations. Ethically you can’t do a trial of people with very low levels without treating them,” senior author Elina Hypp
The data support the 50 nmol/L cut-off endorsed by the United States National Academy of Medicine and align with previous data suggesting the benefit of vitamin D supplementation is largely seen in people with deficiency.
“Everybody with vitamin D levels less than 50 nmol/L is recommended to increase their levels. Our results suggest there’s no need to go very high. The positive message is that if we are able to raise levels to just the current U.S. recommendations, that’s fine. There’s no need to use large supplement doses,” Dr. Hyppönen explained.
Thus, she advised, “Supplementation will clearly help, especially during wintertime or if a person isn’t getting enough vitamin D from the sun or in places where food isn’t fortified with vitamin D.”
But the data don’t support the approach of using large intermittent doses, she added.
“Sometimes doctors want to fix the deficiency quickly with a large ‘bolus’ dose, then continue with a maintenance dose. Increasing evidence suggests that’s not beneficial and might disturb the body’s metabolism so that it can’t get the amount it needs. It’s safe overall but might not work the way we want it to work.”
Rather, Dr. Hyppönen said, “My sense is that daily modest vitamin D dose supplementation when it’s needed is the best way forward.”
Genetic approach reveals causal relationship
The investigators analyzed data from 307,601 individuals in the UK Biobank, a prospective cohort of people recruited from England, Scotland, and Wales during March 2006 and July 2010. Most were of White European ancestry and were aged 37-73 years at baseline.
Genetically predicted vitamin D levels were estimated using 35 confirmed 25-(OH)D variants. Participants were followed for outcomes up to June 2020.
The average baseline measured 25-(OH)D concentration was 45.2 nmol/L, and 11.7% (n = 36,009) of participants had levels between 10.0 and 24.9 nmol/L. Higher levels were seen in people living in southern areas and nonsmokers as well as those with a higher level of physical activity, less socioeconomic deprivation, and lower body mass index.
During follow-up, 6.1% of participants died (n = 18,700). After adjustment for variables, odds ratios for all causes of mortality were highest among people with 25-(OH)D levels below 25 nmol/L and appeared to plateau between 50 and 75 nmol/L, with no further reduction in mortality at values of 75-125 nmol/L.
Mortality 36% higher in those deficient in vitamin D
The risk for mortality was a significant 36% higher for participants with 25-(OH)D 25 nmol/L compared with 50 nmol/L.
With the Mendelian randomization, there was an L-shaped association between genetically predicted 25-(OH)D level and all-cause mortality (P for nonlinearity < .001) and for mortality because of cancer and cardiovascular disease (P for nonlinearity ≤ .033).
Again, the strongest association with those outcomes and genetically predicted 25-(OH)D was found at levels below 25 nmol/L and a plateau was seen by 50 nmol/L.
Compared with a measured 25-(OH)D concentration of 50 nmol/L, investigators estimated that the genetically predicted odds of all-cause mortality would increase sixfold (odds ratio, 6.00) for participants at 10 nmol/L and by 25% (OR, 1.25) for those at 25 nmol/L.
And, compared with a measured 25-(OH)D concentration of 50 nmol/L, those with 10 nmol/L had genetically predicted odds ratios of 5.98 for cardiovascular mortality, 3.37 for cancer mortality, and 12.44 for respiratory mortality.
Comparing measured 25-(OH)D concentrations of 25 nmol/L versus 50 nmol/L, odds ratios for those outcomes were 1.25, 1.16, and 1.96 (95% confidence interval, 1.88-4.67), respectively. All were statistically significant.
Consistent results supportive of a causal effect of genetically predicted 25-(OH)D on all-cause mortality in those with low measured vitamin D concentrations were also found in a sensitivity analysis of 20,837 people of non-White ethnic origin.
The study was funded by the Australian National Health and Medical Research Council. Dr. Sutherland’s studentship is funded by an Australian Research Training Program Scholarship.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Goodbye ‘diabetes insipidus’, hello ‘AVP-D’ and ‘AVP-R’
An international group representing leading endocrinology associations has recommended that the name “diabetes insipidus” – which in some cases has led to harm – be changed to eliminate confusion with “diabetes mellitus” and to reflect the former condition’s pathophysiology.
The new proposed names are arginine vasopressin deficiency (AVP-D) for central (also called “cranial”) etiologies and arginine vasopressin resistance (AVP-R) for nephrogenic (kidney) etiologies.
“What we’re proposing is to rename the disease according to the pathophysiology that defines it,” statement co-author Joseph G. Verbalis, MD, professor of medicine and chief of endocrinology and metabolism at Georgetown University Medical Center, Washington, told this news organization.
The statement advises that henceforth the new names be used in manuscripts and the medical literature while keeping the old names in parentheses during a transition period, as in “AVP-deficiency (cranial diabetes insipidus)” and “AVP-resistance (nephrogenic diabetes insipidus).”
The condition formerly known as diabetes insipidus is relatively rare, occurring in about 1 person per 10-15,000 population. It is caused by either deficient production or resistance in the kidney to the hormone AVP, normally produced by the hypothalamus and stored in the pituitary gland. AVP, also called antidiuretic hormone, regulates the body’s water level and urine production by the kidney.
Both etiologies lead to extreme thirst and excessive production of urine. Common causes of the deficiency include head trauma or brain tumor, while resistance in the kidney is often congenital. It is currently treated with a synthetic form of AVP called desmopressin and fluid replacement.
What’s in a name?
The proposal to change the name by the Working Group for Renaming Diabetes Insipidus is endorsed by The Endocrine Society, European Society of Endocrinology, Pituitary Society, Society for Endocrinology, European Society for Paediatric Endocrinology, Endocrine Society of Australia, Brazilian Endocrine Society, and Japanese Endocrine Society and is under review by several other societies. It was published as a position statement in several of those society’s journals, with more to follow.
Historically, the word “diabetes,” a Greek word meaning “siphon,” was used in the 1st and 2nd century BC to describe excess flow of urine. The Latin word “mellitus” or “honey” was added in the late 17th century to describe the sweetness of the urine in the dysglycemic condition.
A century later, the Latin word “insipidus,” meaning insipid or tasteless, was coined to distinguish between the two types of polyuria, the position statement details.
In the late 19th to early 20th century, the vasopressor and antidiuretic actions of posterior pituitary extracts were discovered and used to treat people with both the central and nephrogenic etiologies, which were also recognized around that time, yet the name “diabetes insipidus” has persisted.
“From a historical perspective, the name is perfectly appropriate. At the time it was identified, and it was realized that it was different from diabetes mellitus, that was a perfectly appropriate terminology based on what was known in the late 19th century – but not now. It has persisted through the years simply because in medicine there’s a lot of inertia for change ... It’s just always been called that. If there’s not a compelling reason to change a name, generally there’s no move to change it,” Dr. Verbalis observed.
‘Dramatic cases of patient mismanagement’ due to name confusion
Unfortunately, the urgency for the change arose from tragedy. In 2009, a 22-year-old man was admitted to the orthopedics department of a London teaching hospital for a hip replacement. Despite his known panhypopituitarism and diabetes insipidus, the nurses continually checked his blood glucose but didn’t give him desmopressin or sufficient fluids. Laboratory testing showed normal glucose, but his serum sodium was 149 mmol/L. The morning after his operation, he had a fatal cardiac arrest with a serum sodium of 169 mmol/L.
“The nurses thought he had diabetes mellitus ... So that was death due to failure to recognize that diabetes insipidus is not diabetes mellitus,” Dr. Verbalis said. “If he had been admitted to endocrinology, this wouldn’t have happened. But he was admitted to orthopedics. Non-endocrinologists are not so aware of diabetes insipidus, because it is a rare disease.”
In 2016, National Health Service England issued a patient safety alert about the “risk of severe harm or death when desmopressin is omitted or delayed in patients with cranial diabetes insipidus,” citing at least four incidents within the prior 7 years where omission of desmopressin had resulted in severe dehydration and death, with another 76 cases of omission or delay that were acted on before the patients became critically ill.
Further impetus for the name change came from the results of an anonymous web-based survey of 1,034 adult and pediatric patients with central diabetes insipidus conducted between August 2021 and February 2022. Overall, 80% reported encountering situations in which their condition had been confused with diabetes mellitus by health care professionals, and 85% supported renaming the disease.
There was some divergence in opinion as to what the new name(s) should be, but clear agreement that the term “diabetes” should not be part of it.
“We’ve only become recently aware that there are dramatic cases of patient mismanagement due to the confusion caused by the word ‘diabetes.’ We think patients should have a voice. If a legitimate patient survey says over 80% think this name should be changed, then I think we as endocrinologists need to pay attention to that,” Dr. Verbalis said.
But while endocrinologists are the ones who see these patients the most often, Dr. Verbalis said a main aim of the position statement “is really to change the mindset of non-endocrinologist doctors and nurses and other health care professionals that this is not diabetes mellitus. It’s a totally different disease. And if we give it a totally different name, then I think they will better recognize that.”
As to how long Dr. Verbalis thinks it will take for the new names to catch on, he pointed out that it’s taken about a decade for the rheumatology field to fully adopt the name “granulomatosis with polyangiitis” as a replacement for “Wegener’s granulomatosis” after the eponymous physician’s Nazi ties were revealed.
“So we’re not anticipating that this is going to change terminology tomorrow. It’s a long process. We just wanted to get the process started,” he said.
Dr. Verbalis has reported consulting for Otsuka.
A version of this article first appeared on Medscape.com.
An international group representing leading endocrinology associations has recommended that the name “diabetes insipidus” – which in some cases has led to harm – be changed to eliminate confusion with “diabetes mellitus” and to reflect the former condition’s pathophysiology.
The new proposed names are arginine vasopressin deficiency (AVP-D) for central (also called “cranial”) etiologies and arginine vasopressin resistance (AVP-R) for nephrogenic (kidney) etiologies.
“What we’re proposing is to rename the disease according to the pathophysiology that defines it,” statement co-author Joseph G. Verbalis, MD, professor of medicine and chief of endocrinology and metabolism at Georgetown University Medical Center, Washington, told this news organization.
The statement advises that henceforth the new names be used in manuscripts and the medical literature while keeping the old names in parentheses during a transition period, as in “AVP-deficiency (cranial diabetes insipidus)” and “AVP-resistance (nephrogenic diabetes insipidus).”
The condition formerly known as diabetes insipidus is relatively rare, occurring in about 1 person per 10-15,000 population. It is caused by either deficient production or resistance in the kidney to the hormone AVP, normally produced by the hypothalamus and stored in the pituitary gland. AVP, also called antidiuretic hormone, regulates the body’s water level and urine production by the kidney.
Both etiologies lead to extreme thirst and excessive production of urine. Common causes of the deficiency include head trauma or brain tumor, while resistance in the kidney is often congenital. It is currently treated with a synthetic form of AVP called desmopressin and fluid replacement.
What’s in a name?
The proposal to change the name by the Working Group for Renaming Diabetes Insipidus is endorsed by The Endocrine Society, European Society of Endocrinology, Pituitary Society, Society for Endocrinology, European Society for Paediatric Endocrinology, Endocrine Society of Australia, Brazilian Endocrine Society, and Japanese Endocrine Society and is under review by several other societies. It was published as a position statement in several of those society’s journals, with more to follow.
Historically, the word “diabetes,” a Greek word meaning “siphon,” was used in the 1st and 2nd century BC to describe excess flow of urine. The Latin word “mellitus” or “honey” was added in the late 17th century to describe the sweetness of the urine in the dysglycemic condition.
A century later, the Latin word “insipidus,” meaning insipid or tasteless, was coined to distinguish between the two types of polyuria, the position statement details.
In the late 19th to early 20th century, the vasopressor and antidiuretic actions of posterior pituitary extracts were discovered and used to treat people with both the central and nephrogenic etiologies, which were also recognized around that time, yet the name “diabetes insipidus” has persisted.
“From a historical perspective, the name is perfectly appropriate. At the time it was identified, and it was realized that it was different from diabetes mellitus, that was a perfectly appropriate terminology based on what was known in the late 19th century – but not now. It has persisted through the years simply because in medicine there’s a lot of inertia for change ... It’s just always been called that. If there’s not a compelling reason to change a name, generally there’s no move to change it,” Dr. Verbalis observed.
‘Dramatic cases of patient mismanagement’ due to name confusion
Unfortunately, the urgency for the change arose from tragedy. In 2009, a 22-year-old man was admitted to the orthopedics department of a London teaching hospital for a hip replacement. Despite his known panhypopituitarism and diabetes insipidus, the nurses continually checked his blood glucose but didn’t give him desmopressin or sufficient fluids. Laboratory testing showed normal glucose, but his serum sodium was 149 mmol/L. The morning after his operation, he had a fatal cardiac arrest with a serum sodium of 169 mmol/L.
“The nurses thought he had diabetes mellitus ... So that was death due to failure to recognize that diabetes insipidus is not diabetes mellitus,” Dr. Verbalis said. “If he had been admitted to endocrinology, this wouldn’t have happened. But he was admitted to orthopedics. Non-endocrinologists are not so aware of diabetes insipidus, because it is a rare disease.”
In 2016, National Health Service England issued a patient safety alert about the “risk of severe harm or death when desmopressin is omitted or delayed in patients with cranial diabetes insipidus,” citing at least four incidents within the prior 7 years where omission of desmopressin had resulted in severe dehydration and death, with another 76 cases of omission or delay that were acted on before the patients became critically ill.
Further impetus for the name change came from the results of an anonymous web-based survey of 1,034 adult and pediatric patients with central diabetes insipidus conducted between August 2021 and February 2022. Overall, 80% reported encountering situations in which their condition had been confused with diabetes mellitus by health care professionals, and 85% supported renaming the disease.
There was some divergence in opinion as to what the new name(s) should be, but clear agreement that the term “diabetes” should not be part of it.
“We’ve only become recently aware that there are dramatic cases of patient mismanagement due to the confusion caused by the word ‘diabetes.’ We think patients should have a voice. If a legitimate patient survey says over 80% think this name should be changed, then I think we as endocrinologists need to pay attention to that,” Dr. Verbalis said.
But while endocrinologists are the ones who see these patients the most often, Dr. Verbalis said a main aim of the position statement “is really to change the mindset of non-endocrinologist doctors and nurses and other health care professionals that this is not diabetes mellitus. It’s a totally different disease. And if we give it a totally different name, then I think they will better recognize that.”
As to how long Dr. Verbalis thinks it will take for the new names to catch on, he pointed out that it’s taken about a decade for the rheumatology field to fully adopt the name “granulomatosis with polyangiitis” as a replacement for “Wegener’s granulomatosis” after the eponymous physician’s Nazi ties were revealed.
“So we’re not anticipating that this is going to change terminology tomorrow. It’s a long process. We just wanted to get the process started,” he said.
Dr. Verbalis has reported consulting for Otsuka.
A version of this article first appeared on Medscape.com.
An international group representing leading endocrinology associations has recommended that the name “diabetes insipidus” – which in some cases has led to harm – be changed to eliminate confusion with “diabetes mellitus” and to reflect the former condition’s pathophysiology.
The new proposed names are arginine vasopressin deficiency (AVP-D) for central (also called “cranial”) etiologies and arginine vasopressin resistance (AVP-R) for nephrogenic (kidney) etiologies.
“What we’re proposing is to rename the disease according to the pathophysiology that defines it,” statement co-author Joseph G. Verbalis, MD, professor of medicine and chief of endocrinology and metabolism at Georgetown University Medical Center, Washington, told this news organization.
The statement advises that henceforth the new names be used in manuscripts and the medical literature while keeping the old names in parentheses during a transition period, as in “AVP-deficiency (cranial diabetes insipidus)” and “AVP-resistance (nephrogenic diabetes insipidus).”
The condition formerly known as diabetes insipidus is relatively rare, occurring in about 1 person per 10-15,000 population. It is caused by either deficient production or resistance in the kidney to the hormone AVP, normally produced by the hypothalamus and stored in the pituitary gland. AVP, also called antidiuretic hormone, regulates the body’s water level and urine production by the kidney.
Both etiologies lead to extreme thirst and excessive production of urine. Common causes of the deficiency include head trauma or brain tumor, while resistance in the kidney is often congenital. It is currently treated with a synthetic form of AVP called desmopressin and fluid replacement.
What’s in a name?
The proposal to change the name by the Working Group for Renaming Diabetes Insipidus is endorsed by The Endocrine Society, European Society of Endocrinology, Pituitary Society, Society for Endocrinology, European Society for Paediatric Endocrinology, Endocrine Society of Australia, Brazilian Endocrine Society, and Japanese Endocrine Society and is under review by several other societies. It was published as a position statement in several of those society’s journals, with more to follow.
Historically, the word “diabetes,” a Greek word meaning “siphon,” was used in the 1st and 2nd century BC to describe excess flow of urine. The Latin word “mellitus” or “honey” was added in the late 17th century to describe the sweetness of the urine in the dysglycemic condition.
A century later, the Latin word “insipidus,” meaning insipid or tasteless, was coined to distinguish between the two types of polyuria, the position statement details.
In the late 19th to early 20th century, the vasopressor and antidiuretic actions of posterior pituitary extracts were discovered and used to treat people with both the central and nephrogenic etiologies, which were also recognized around that time, yet the name “diabetes insipidus” has persisted.
“From a historical perspective, the name is perfectly appropriate. At the time it was identified, and it was realized that it was different from diabetes mellitus, that was a perfectly appropriate terminology based on what was known in the late 19th century – but not now. It has persisted through the years simply because in medicine there’s a lot of inertia for change ... It’s just always been called that. If there’s not a compelling reason to change a name, generally there’s no move to change it,” Dr. Verbalis observed.
‘Dramatic cases of patient mismanagement’ due to name confusion
Unfortunately, the urgency for the change arose from tragedy. In 2009, a 22-year-old man was admitted to the orthopedics department of a London teaching hospital for a hip replacement. Despite his known panhypopituitarism and diabetes insipidus, the nurses continually checked his blood glucose but didn’t give him desmopressin or sufficient fluids. Laboratory testing showed normal glucose, but his serum sodium was 149 mmol/L. The morning after his operation, he had a fatal cardiac arrest with a serum sodium of 169 mmol/L.
“The nurses thought he had diabetes mellitus ... So that was death due to failure to recognize that diabetes insipidus is not diabetes mellitus,” Dr. Verbalis said. “If he had been admitted to endocrinology, this wouldn’t have happened. But he was admitted to orthopedics. Non-endocrinologists are not so aware of diabetes insipidus, because it is a rare disease.”
In 2016, National Health Service England issued a patient safety alert about the “risk of severe harm or death when desmopressin is omitted or delayed in patients with cranial diabetes insipidus,” citing at least four incidents within the prior 7 years where omission of desmopressin had resulted in severe dehydration and death, with another 76 cases of omission or delay that were acted on before the patients became critically ill.
Further impetus for the name change came from the results of an anonymous web-based survey of 1,034 adult and pediatric patients with central diabetes insipidus conducted between August 2021 and February 2022. Overall, 80% reported encountering situations in which their condition had been confused with diabetes mellitus by health care professionals, and 85% supported renaming the disease.
There was some divergence in opinion as to what the new name(s) should be, but clear agreement that the term “diabetes” should not be part of it.
“We’ve only become recently aware that there are dramatic cases of patient mismanagement due to the confusion caused by the word ‘diabetes.’ We think patients should have a voice. If a legitimate patient survey says over 80% think this name should be changed, then I think we as endocrinologists need to pay attention to that,” Dr. Verbalis said.
But while endocrinologists are the ones who see these patients the most often, Dr. Verbalis said a main aim of the position statement “is really to change the mindset of non-endocrinologist doctors and nurses and other health care professionals that this is not diabetes mellitus. It’s a totally different disease. And if we give it a totally different name, then I think they will better recognize that.”
As to how long Dr. Verbalis thinks it will take for the new names to catch on, he pointed out that it’s taken about a decade for the rheumatology field to fully adopt the name “granulomatosis with polyangiitis” as a replacement for “Wegener’s granulomatosis” after the eponymous physician’s Nazi ties were revealed.
“So we’re not anticipating that this is going to change terminology tomorrow. It’s a long process. We just wanted to get the process started,” he said.
Dr. Verbalis has reported consulting for Otsuka.
A version of this article first appeared on Medscape.com.
Islet transplants in type 1 diabetes durable up to 8 years
Transplantation of cadaveric pancreatic islet cells resulted in graft survival and function with acceptable safety for up to 8 years in selected individuals with type 1 diabetes, new research finds.
The study is a long-term follow-up of two phase 3 pivotal trials from the Clinical Islet Transplantation Consortium of a purified human pancreatic islet cell product for treating people with type 1 diabetes.
One trial involved islet transplantation in 48 people who experienced severe hypoglycemia and hypoglycemic unawareness, and the other trial included 24 people who also experienced those complications and were already receiving immunosuppression following kidney transplant. The trials, both registered with the U.S. Food and Drug Administration (FDA), met their primary efficacy and safety endpoints at 2- and 3-year timepoints.
The follow-up data have now been published in Diabetes Care by Michael Rickels, MD, and colleagues.
The procedure involved infusion through the hepatic portal vein of one or more purified human pancreatic islet products under standardized immunosuppression using methods that Dr. Rickels and colleagues have been developing since 2004. The approach involves multiple modalities to protect the islets prior to transplantation.
Among the 34 islet-alone and eight islet-after–kidney transplant recipients who entered the extended follow-up, durable graft survival allowing for achievement of glycemic targets occurred without severe hypoglycemia or adverse effects from immunosuppression.
The primary outcome, actuarial survival of graft islet function, was 56% at the maximum follow-up of 8.3 years for the islet-only transplantation group and 49% at 7.3 years for the islet-after–kidney transplantation group (P = .004).
The findings suggest that “in the long run, islet transplantation has efficacy, including among those who have had kidney transplants ... Most type 1 diabetes patients are improved tremendously with current insulin delivery systems ... but for those having the most difficulty controlling their blood sugar – and those whose diabetes has already been complicated by needing a kidney transplant – the outcomes we saw in this study are what we’ve been hoping to achieve for more than 20 years,” said Dr. Rickels in a statement from his institution, the University of Pennsylvania, Philadelphia.
In the initial trials at day 75 after the initial transplant, 87.5% of the islet-alone and 71% of the islet-after–kidney transplant group achieved hemoglobin A1c under 7%, and 85% and 54%, respectively, achieved A1c at or under 6.5%. At the end of maximal follow-up, 49% of islet-only transplant recipients maintained A1c under 7%, although none had A1c at or under 6.5%. For the islet-after–kidney transplant group, these proportions were 35% and 17%, respectively (P = .0017 for A1c under 7.0% and P < .0001 for A1c ≤ 6.5%, respectively, between the groups).
There were 12 severe hypoglycemic episodes in five patients (three islet-alone and two islet-after–kidney transplant group) during the initial trials, but no additional episodes occurred in either group during long-term follow-up.
Overall, 53 individuals – 37 in the islet-alone and 16 in the islet-after–kidney transplant group – or 74% of the total, achieved a period of insulin independence with A1c under 7%, ranging from 36 to 481 days. The range of time to achieving insulin independence reflects individuals who received one, two, or three islet infusions.
The fact that most patients achieved insulin independence following just one (n = 20) or two (n = 30) infusions and only three patients required three infusions was notable, Dr. Rickels said.
“Currently, around the world, there’s an expectation of two to three donor pancreases being needed. Here, it’s one, maybe two. It’s a much more efficient protocol and opens up access for more islet transplantation as a hoped-for alternative to pancreas transplants.”
Of those who achieved insulin independence, 30 (57%) remained insulin-independent throughout follow-up (20 of 37 islet-alone and 10 of 16 islet-after–kidney transplant patients), with no difference in duration of insulin independence between the groups.
There were no deaths during post-transplant follow-up. Rates of serious adverse events were 0.31 and 0.43 per patient-year for the islet-after–kidney and islet-alone transplant groups, respectively. Of a total of 104 serious adverse events, 65 occurred during the initial trials and had been previously reported. Of the additional 39 serious adverse events that occurred during long-term follow-up, 11 were possibly due to immunosuppression and 27 were deemed unrelated to the procedures.
According to Dr. Rickels, “These are the most seriously affected patients, and you’d be expecting to see some hospitalizations in a population managed on immunosuppression therapy ... It’s important to note that none of the adverse events were related to the actual islet product. Also, kidney function remained stable during long-term follow-up in both cohorts, in fact, improving in those who had kidney transplants.”
Overall, he said, “This is a much less invasive procedure that opens itself up to significantly fewer complications than what many of these patients would otherwise require, a pancreas transplant, which involves major abdominal surgery.”
The investigators plan to submit these data as part of a biologic license application (BLA) to the FDA.
The research was supported by grants from JDRF, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Allergy and Infectious Diseases. Dr. Rickels has reported receiving consulting fees from Sernova and Vertex Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Transplantation of cadaveric pancreatic islet cells resulted in graft survival and function with acceptable safety for up to 8 years in selected individuals with type 1 diabetes, new research finds.
The study is a long-term follow-up of two phase 3 pivotal trials from the Clinical Islet Transplantation Consortium of a purified human pancreatic islet cell product for treating people with type 1 diabetes.
One trial involved islet transplantation in 48 people who experienced severe hypoglycemia and hypoglycemic unawareness, and the other trial included 24 people who also experienced those complications and were already receiving immunosuppression following kidney transplant. The trials, both registered with the U.S. Food and Drug Administration (FDA), met their primary efficacy and safety endpoints at 2- and 3-year timepoints.
The follow-up data have now been published in Diabetes Care by Michael Rickels, MD, and colleagues.
The procedure involved infusion through the hepatic portal vein of one or more purified human pancreatic islet products under standardized immunosuppression using methods that Dr. Rickels and colleagues have been developing since 2004. The approach involves multiple modalities to protect the islets prior to transplantation.
Among the 34 islet-alone and eight islet-after–kidney transplant recipients who entered the extended follow-up, durable graft survival allowing for achievement of glycemic targets occurred without severe hypoglycemia or adverse effects from immunosuppression.
The primary outcome, actuarial survival of graft islet function, was 56% at the maximum follow-up of 8.3 years for the islet-only transplantation group and 49% at 7.3 years for the islet-after–kidney transplantation group (P = .004).
The findings suggest that “in the long run, islet transplantation has efficacy, including among those who have had kidney transplants ... Most type 1 diabetes patients are improved tremendously with current insulin delivery systems ... but for those having the most difficulty controlling their blood sugar – and those whose diabetes has already been complicated by needing a kidney transplant – the outcomes we saw in this study are what we’ve been hoping to achieve for more than 20 years,” said Dr. Rickels in a statement from his institution, the University of Pennsylvania, Philadelphia.
In the initial trials at day 75 after the initial transplant, 87.5% of the islet-alone and 71% of the islet-after–kidney transplant group achieved hemoglobin A1c under 7%, and 85% and 54%, respectively, achieved A1c at or under 6.5%. At the end of maximal follow-up, 49% of islet-only transplant recipients maintained A1c under 7%, although none had A1c at or under 6.5%. For the islet-after–kidney transplant group, these proportions were 35% and 17%, respectively (P = .0017 for A1c under 7.0% and P < .0001 for A1c ≤ 6.5%, respectively, between the groups).
There were 12 severe hypoglycemic episodes in five patients (three islet-alone and two islet-after–kidney transplant group) during the initial trials, but no additional episodes occurred in either group during long-term follow-up.
Overall, 53 individuals – 37 in the islet-alone and 16 in the islet-after–kidney transplant group – or 74% of the total, achieved a period of insulin independence with A1c under 7%, ranging from 36 to 481 days. The range of time to achieving insulin independence reflects individuals who received one, two, or three islet infusions.
The fact that most patients achieved insulin independence following just one (n = 20) or two (n = 30) infusions and only three patients required three infusions was notable, Dr. Rickels said.
“Currently, around the world, there’s an expectation of two to three donor pancreases being needed. Here, it’s one, maybe two. It’s a much more efficient protocol and opens up access for more islet transplantation as a hoped-for alternative to pancreas transplants.”
Of those who achieved insulin independence, 30 (57%) remained insulin-independent throughout follow-up (20 of 37 islet-alone and 10 of 16 islet-after–kidney transplant patients), with no difference in duration of insulin independence between the groups.
There were no deaths during post-transplant follow-up. Rates of serious adverse events were 0.31 and 0.43 per patient-year for the islet-after–kidney and islet-alone transplant groups, respectively. Of a total of 104 serious adverse events, 65 occurred during the initial trials and had been previously reported. Of the additional 39 serious adverse events that occurred during long-term follow-up, 11 were possibly due to immunosuppression and 27 were deemed unrelated to the procedures.
According to Dr. Rickels, “These are the most seriously affected patients, and you’d be expecting to see some hospitalizations in a population managed on immunosuppression therapy ... It’s important to note that none of the adverse events were related to the actual islet product. Also, kidney function remained stable during long-term follow-up in both cohorts, in fact, improving in those who had kidney transplants.”
Overall, he said, “This is a much less invasive procedure that opens itself up to significantly fewer complications than what many of these patients would otherwise require, a pancreas transplant, which involves major abdominal surgery.”
The investigators plan to submit these data as part of a biologic license application (BLA) to the FDA.
The research was supported by grants from JDRF, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Allergy and Infectious Diseases. Dr. Rickels has reported receiving consulting fees from Sernova and Vertex Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Transplantation of cadaveric pancreatic islet cells resulted in graft survival and function with acceptable safety for up to 8 years in selected individuals with type 1 diabetes, new research finds.
The study is a long-term follow-up of two phase 3 pivotal trials from the Clinical Islet Transplantation Consortium of a purified human pancreatic islet cell product for treating people with type 1 diabetes.
One trial involved islet transplantation in 48 people who experienced severe hypoglycemia and hypoglycemic unawareness, and the other trial included 24 people who also experienced those complications and were already receiving immunosuppression following kidney transplant. The trials, both registered with the U.S. Food and Drug Administration (FDA), met their primary efficacy and safety endpoints at 2- and 3-year timepoints.
The follow-up data have now been published in Diabetes Care by Michael Rickels, MD, and colleagues.
The procedure involved infusion through the hepatic portal vein of one or more purified human pancreatic islet products under standardized immunosuppression using methods that Dr. Rickels and colleagues have been developing since 2004. The approach involves multiple modalities to protect the islets prior to transplantation.
Among the 34 islet-alone and eight islet-after–kidney transplant recipients who entered the extended follow-up, durable graft survival allowing for achievement of glycemic targets occurred without severe hypoglycemia or adverse effects from immunosuppression.
The primary outcome, actuarial survival of graft islet function, was 56% at the maximum follow-up of 8.3 years for the islet-only transplantation group and 49% at 7.3 years for the islet-after–kidney transplantation group (P = .004).
The findings suggest that “in the long run, islet transplantation has efficacy, including among those who have had kidney transplants ... Most type 1 diabetes patients are improved tremendously with current insulin delivery systems ... but for those having the most difficulty controlling their blood sugar – and those whose diabetes has already been complicated by needing a kidney transplant – the outcomes we saw in this study are what we’ve been hoping to achieve for more than 20 years,” said Dr. Rickels in a statement from his institution, the University of Pennsylvania, Philadelphia.
In the initial trials at day 75 after the initial transplant, 87.5% of the islet-alone and 71% of the islet-after–kidney transplant group achieved hemoglobin A1c under 7%, and 85% and 54%, respectively, achieved A1c at or under 6.5%. At the end of maximal follow-up, 49% of islet-only transplant recipients maintained A1c under 7%, although none had A1c at or under 6.5%. For the islet-after–kidney transplant group, these proportions were 35% and 17%, respectively (P = .0017 for A1c under 7.0% and P < .0001 for A1c ≤ 6.5%, respectively, between the groups).
There were 12 severe hypoglycemic episodes in five patients (three islet-alone and two islet-after–kidney transplant group) during the initial trials, but no additional episodes occurred in either group during long-term follow-up.
Overall, 53 individuals – 37 in the islet-alone and 16 in the islet-after–kidney transplant group – or 74% of the total, achieved a period of insulin independence with A1c under 7%, ranging from 36 to 481 days. The range of time to achieving insulin independence reflects individuals who received one, two, or three islet infusions.
The fact that most patients achieved insulin independence following just one (n = 20) or two (n = 30) infusions and only three patients required three infusions was notable, Dr. Rickels said.
“Currently, around the world, there’s an expectation of two to three donor pancreases being needed. Here, it’s one, maybe two. It’s a much more efficient protocol and opens up access for more islet transplantation as a hoped-for alternative to pancreas transplants.”
Of those who achieved insulin independence, 30 (57%) remained insulin-independent throughout follow-up (20 of 37 islet-alone and 10 of 16 islet-after–kidney transplant patients), with no difference in duration of insulin independence between the groups.
There were no deaths during post-transplant follow-up. Rates of serious adverse events were 0.31 and 0.43 per patient-year for the islet-after–kidney and islet-alone transplant groups, respectively. Of a total of 104 serious adverse events, 65 occurred during the initial trials and had been previously reported. Of the additional 39 serious adverse events that occurred during long-term follow-up, 11 were possibly due to immunosuppression and 27 were deemed unrelated to the procedures.
According to Dr. Rickels, “These are the most seriously affected patients, and you’d be expecting to see some hospitalizations in a population managed on immunosuppression therapy ... It’s important to note that none of the adverse events were related to the actual islet product. Also, kidney function remained stable during long-term follow-up in both cohorts, in fact, improving in those who had kidney transplants.”
Overall, he said, “This is a much less invasive procedure that opens itself up to significantly fewer complications than what many of these patients would otherwise require, a pancreas transplant, which involves major abdominal surgery.”
The investigators plan to submit these data as part of a biologic license application (BLA) to the FDA.
The research was supported by grants from JDRF, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Allergy and Infectious Diseases. Dr. Rickels has reported receiving consulting fees from Sernova and Vertex Pharmaceuticals.
A version of this article first appeared on Medscape.com.
FROM DIABETES CARE
Insulin rationing common, ‘surprising’ even among privately insured
Insulin rationing due to cost in the United States is common even among people with diabetes who have private health insurance, new data show.
The findings from the 2021 National Health Interview Survey (NHIS) suggest that about one in six people with insulin-treated diabetes in the United States practice insulin rationing – skipping doses, taking less insulin than needed, or delaying the purchase of insulin – because of the price.
Not surprisingly, those without insurance had the highest rationing rate, at nearly a third. However, those with private insurance also had higher rates, at nearly one in five, than those of the overall diabetes population. And those with public insurance – Medicare and Medicaid – had lower rates.
The finding regarding privately insured individuals was “somewhat surprising,” lead author Adam Gaffney, MD, told this news organization. But he noted that the finding likely reflects issues such as copays and deductibles, along with other barriers patients experience within the private health insurance system.
The authors pointed out that the $35 copay cap on insulin included in the Inflation Reduction Act of 2022 might improve insulin access for Medicare beneficiaries but a similar cap for privately insured people was removed from the bill. Moreover, copay caps don’t help people who are uninsured.
And, although some states have also passed insulin copay caps that apply to privately insured people, “even a monthly cost of $35 can be a lot of money for people with low incomes. That isn’t negligible. It’s important to keep that in mind,” said Dr. Gaffney, a pulmonary and critical care physician at Harvard Medical School, Boston, and Cambridge (Mass.) Health Alliance.
“Insulin rationing is frequently harmful and sometimes deadly. In the ICU, I have cared for patients who have life-threatening complications of diabetes because they couldn’t afford this life-saving drug. Universal access to insulin, without cost barriers, is urgently needed,” Dr. Gaffney said in a Public Citizen statement.
Senior author Steffie Woolhandler, MD, agrees. “Drug companies have ramped up prices on insulin year after year, even for products that remain completely unchanged,” she noted.
“Drug firms are making vast profits at the expense of the health, and even the lives, of patients,” noted Dr. Woolhandler, a distinguished professor at Hunter College, City University of New York, a lecturer in medicine at Harvard, and a research associate at Public Citizen.
Uninsured, privately insured, and younger people more likely to ration
Dr. Gaffney and colleagues’ findings were published online in Annals of Internal Medicine.
The study is the first to examine insulin rationing across the United States among people with all diabetes types treated with insulin using the nationally representative NHIS data.
The results are consistent with those of previous studies, which have found similar rates of insulin rationing at a single U.S. institution and internationally among just those with type 1 diabetes, Dr. Gaffney noted.
In 2021, questions about insulin rationing were added to the NHIS for the first time.
The sample included 982 insulin users with diabetes, representing about 1.4 million U.S. adults with type 1 diabetes, 5.8 million with type 2 diabetes, and 0.4 million with other/unknown types.
Overall, 16.5% of participants – 1.3 million nationwide – reported skipping or reducing insulin doses or delaying the purchase of it in the past year. Delaying purchase was the most common type of rationing, reported by 14.2%, while taking less than needed was the most common practice among those with type 1 diabetes (16.5%).
Age made a difference, with 11.2% of adults aged 65 or older versus 20.4% of younger people reporting rationing. And by income level, even among those at the top level examined – 400% or higher of the federal poverty line – 10.8% reported rationing.
“The high-income group is not necessarily rich. Many would be considered middle-income,” Dr. Gaffney pointed out.
By race, 23.2% of Black participants reported rationing compared with 16.0% of White and Hispanic individuals.
People without insurance had the highest rationing rate (29.2%), followed by those with private insurance (18.8%), other coverage (16.1%), Medicare (13.5%), and Medicaid (11.6%).
‘It’s a complicated system’
Dr. Gaffney noted that even when the patient has private insurance, it’s challenging for the clinician to know in advance whether there are formulary restrictions on what type of insulin can be prescribed or what the patient’s copay or deductible will be.
“Often the prescription gets written without clear knowledge of coverage beforehand ... Coverage differs from patient to patient, from insurance to insurance. It’s a complicated system.”
He added, though, that some electronic health records (EHRs) incorporate this information. “Currently, some EHRs give real-time feedback. I see no reason why, for all the money we plug into these EHRs, there couldn’t be real-time feedback for every patient so you know what the copay is and whether it’s covered at the time you’re prescribing it. To me that’s a very straightforward technological fix that we could achieve. We have the information, but it’s hard to act on it.”
But beyond the EHR, “there are also problems when the patient’s insurance changes or their network changes, and what insulin is covered changes. And they don’t necessarily get that new prescription in time. And suddenly they have a gap. Gaps can be dangerous.”
What’s more, Dr. Gaffney noted: “The study raises concerning questions about what happens when the public health emergency ends and millions of people with Medicaid lose their coverage. Where are they going to get insulin? That’s another population we have to be worried about.”
All of this puts clinicians in a difficult spot, he said.
“They want the best for their patients but they’re working in a system that’s not letting them focus on practicing medicine and instead is forcing them to think about these economic issues that are in large part out of their control.”
Dr. Gaffney is a member of Physicians for a National Health Program, which advocates for a single-payer health system in the United States.
A version of this article first appeared on Medscape.com.
Insulin rationing due to cost in the United States is common even among people with diabetes who have private health insurance, new data show.
The findings from the 2021 National Health Interview Survey (NHIS) suggest that about one in six people with insulin-treated diabetes in the United States practice insulin rationing – skipping doses, taking less insulin than needed, or delaying the purchase of insulin – because of the price.
Not surprisingly, those without insurance had the highest rationing rate, at nearly a third. However, those with private insurance also had higher rates, at nearly one in five, than those of the overall diabetes population. And those with public insurance – Medicare and Medicaid – had lower rates.
The finding regarding privately insured individuals was “somewhat surprising,” lead author Adam Gaffney, MD, told this news organization. But he noted that the finding likely reflects issues such as copays and deductibles, along with other barriers patients experience within the private health insurance system.
The authors pointed out that the $35 copay cap on insulin included in the Inflation Reduction Act of 2022 might improve insulin access for Medicare beneficiaries but a similar cap for privately insured people was removed from the bill. Moreover, copay caps don’t help people who are uninsured.
And, although some states have also passed insulin copay caps that apply to privately insured people, “even a monthly cost of $35 can be a lot of money for people with low incomes. That isn’t negligible. It’s important to keep that in mind,” said Dr. Gaffney, a pulmonary and critical care physician at Harvard Medical School, Boston, and Cambridge (Mass.) Health Alliance.
“Insulin rationing is frequently harmful and sometimes deadly. In the ICU, I have cared for patients who have life-threatening complications of diabetes because they couldn’t afford this life-saving drug. Universal access to insulin, without cost barriers, is urgently needed,” Dr. Gaffney said in a Public Citizen statement.
Senior author Steffie Woolhandler, MD, agrees. “Drug companies have ramped up prices on insulin year after year, even for products that remain completely unchanged,” she noted.
“Drug firms are making vast profits at the expense of the health, and even the lives, of patients,” noted Dr. Woolhandler, a distinguished professor at Hunter College, City University of New York, a lecturer in medicine at Harvard, and a research associate at Public Citizen.
Uninsured, privately insured, and younger people more likely to ration
Dr. Gaffney and colleagues’ findings were published online in Annals of Internal Medicine.
The study is the first to examine insulin rationing across the United States among people with all diabetes types treated with insulin using the nationally representative NHIS data.
The results are consistent with those of previous studies, which have found similar rates of insulin rationing at a single U.S. institution and internationally among just those with type 1 diabetes, Dr. Gaffney noted.
In 2021, questions about insulin rationing were added to the NHIS for the first time.
The sample included 982 insulin users with diabetes, representing about 1.4 million U.S. adults with type 1 diabetes, 5.8 million with type 2 diabetes, and 0.4 million with other/unknown types.
Overall, 16.5% of participants – 1.3 million nationwide – reported skipping or reducing insulin doses or delaying the purchase of it in the past year. Delaying purchase was the most common type of rationing, reported by 14.2%, while taking less than needed was the most common practice among those with type 1 diabetes (16.5%).
Age made a difference, with 11.2% of adults aged 65 or older versus 20.4% of younger people reporting rationing. And by income level, even among those at the top level examined – 400% or higher of the federal poverty line – 10.8% reported rationing.
“The high-income group is not necessarily rich. Many would be considered middle-income,” Dr. Gaffney pointed out.
By race, 23.2% of Black participants reported rationing compared with 16.0% of White and Hispanic individuals.
People without insurance had the highest rationing rate (29.2%), followed by those with private insurance (18.8%), other coverage (16.1%), Medicare (13.5%), and Medicaid (11.6%).
‘It’s a complicated system’
Dr. Gaffney noted that even when the patient has private insurance, it’s challenging for the clinician to know in advance whether there are formulary restrictions on what type of insulin can be prescribed or what the patient’s copay or deductible will be.
“Often the prescription gets written without clear knowledge of coverage beforehand ... Coverage differs from patient to patient, from insurance to insurance. It’s a complicated system.”
He added, though, that some electronic health records (EHRs) incorporate this information. “Currently, some EHRs give real-time feedback. I see no reason why, for all the money we plug into these EHRs, there couldn’t be real-time feedback for every patient so you know what the copay is and whether it’s covered at the time you’re prescribing it. To me that’s a very straightforward technological fix that we could achieve. We have the information, but it’s hard to act on it.”
But beyond the EHR, “there are also problems when the patient’s insurance changes or their network changes, and what insulin is covered changes. And they don’t necessarily get that new prescription in time. And suddenly they have a gap. Gaps can be dangerous.”
What’s more, Dr. Gaffney noted: “The study raises concerning questions about what happens when the public health emergency ends and millions of people with Medicaid lose their coverage. Where are they going to get insulin? That’s another population we have to be worried about.”
All of this puts clinicians in a difficult spot, he said.
“They want the best for their patients but they’re working in a system that’s not letting them focus on practicing medicine and instead is forcing them to think about these economic issues that are in large part out of their control.”
Dr. Gaffney is a member of Physicians for a National Health Program, which advocates for a single-payer health system in the United States.
A version of this article first appeared on Medscape.com.
Insulin rationing due to cost in the United States is common even among people with diabetes who have private health insurance, new data show.
The findings from the 2021 National Health Interview Survey (NHIS) suggest that about one in six people with insulin-treated diabetes in the United States practice insulin rationing – skipping doses, taking less insulin than needed, or delaying the purchase of insulin – because of the price.
Not surprisingly, those without insurance had the highest rationing rate, at nearly a third. However, those with private insurance also had higher rates, at nearly one in five, than those of the overall diabetes population. And those with public insurance – Medicare and Medicaid – had lower rates.
The finding regarding privately insured individuals was “somewhat surprising,” lead author Adam Gaffney, MD, told this news organization. But he noted that the finding likely reflects issues such as copays and deductibles, along with other barriers patients experience within the private health insurance system.
The authors pointed out that the $35 copay cap on insulin included in the Inflation Reduction Act of 2022 might improve insulin access for Medicare beneficiaries but a similar cap for privately insured people was removed from the bill. Moreover, copay caps don’t help people who are uninsured.
And, although some states have also passed insulin copay caps that apply to privately insured people, “even a monthly cost of $35 can be a lot of money for people with low incomes. That isn’t negligible. It’s important to keep that in mind,” said Dr. Gaffney, a pulmonary and critical care physician at Harvard Medical School, Boston, and Cambridge (Mass.) Health Alliance.
“Insulin rationing is frequently harmful and sometimes deadly. In the ICU, I have cared for patients who have life-threatening complications of diabetes because they couldn’t afford this life-saving drug. Universal access to insulin, without cost barriers, is urgently needed,” Dr. Gaffney said in a Public Citizen statement.
Senior author Steffie Woolhandler, MD, agrees. “Drug companies have ramped up prices on insulin year after year, even for products that remain completely unchanged,” she noted.
“Drug firms are making vast profits at the expense of the health, and even the lives, of patients,” noted Dr. Woolhandler, a distinguished professor at Hunter College, City University of New York, a lecturer in medicine at Harvard, and a research associate at Public Citizen.
Uninsured, privately insured, and younger people more likely to ration
Dr. Gaffney and colleagues’ findings were published online in Annals of Internal Medicine.
The study is the first to examine insulin rationing across the United States among people with all diabetes types treated with insulin using the nationally representative NHIS data.
The results are consistent with those of previous studies, which have found similar rates of insulin rationing at a single U.S. institution and internationally among just those with type 1 diabetes, Dr. Gaffney noted.
In 2021, questions about insulin rationing were added to the NHIS for the first time.
The sample included 982 insulin users with diabetes, representing about 1.4 million U.S. adults with type 1 diabetes, 5.8 million with type 2 diabetes, and 0.4 million with other/unknown types.
Overall, 16.5% of participants – 1.3 million nationwide – reported skipping or reducing insulin doses or delaying the purchase of it in the past year. Delaying purchase was the most common type of rationing, reported by 14.2%, while taking less than needed was the most common practice among those with type 1 diabetes (16.5%).
Age made a difference, with 11.2% of adults aged 65 or older versus 20.4% of younger people reporting rationing. And by income level, even among those at the top level examined – 400% or higher of the federal poverty line – 10.8% reported rationing.
“The high-income group is not necessarily rich. Many would be considered middle-income,” Dr. Gaffney pointed out.
By race, 23.2% of Black participants reported rationing compared with 16.0% of White and Hispanic individuals.
People without insurance had the highest rationing rate (29.2%), followed by those with private insurance (18.8%), other coverage (16.1%), Medicare (13.5%), and Medicaid (11.6%).
‘It’s a complicated system’
Dr. Gaffney noted that even when the patient has private insurance, it’s challenging for the clinician to know in advance whether there are formulary restrictions on what type of insulin can be prescribed or what the patient’s copay or deductible will be.
“Often the prescription gets written without clear knowledge of coverage beforehand ... Coverage differs from patient to patient, from insurance to insurance. It’s a complicated system.”
He added, though, that some electronic health records (EHRs) incorporate this information. “Currently, some EHRs give real-time feedback. I see no reason why, for all the money we plug into these EHRs, there couldn’t be real-time feedback for every patient so you know what the copay is and whether it’s covered at the time you’re prescribing it. To me that’s a very straightforward technological fix that we could achieve. We have the information, but it’s hard to act on it.”
But beyond the EHR, “there are also problems when the patient’s insurance changes or their network changes, and what insulin is covered changes. And they don’t necessarily get that new prescription in time. And suddenly they have a gap. Gaps can be dangerous.”
What’s more, Dr. Gaffney noted: “The study raises concerning questions about what happens when the public health emergency ends and millions of people with Medicaid lose their coverage. Where are they going to get insulin? That’s another population we have to be worried about.”
All of this puts clinicians in a difficult spot, he said.
“They want the best for their patients but they’re working in a system that’s not letting them focus on practicing medicine and instead is forcing them to think about these economic issues that are in large part out of their control.”
Dr. Gaffney is a member of Physicians for a National Health Program, which advocates for a single-payer health system in the United States.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Older diabetes drugs linked to dementia risk -- one lower, one higher
a new observational study in patients with type 2 diabetes suggests.
The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.
“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.
The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.
“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
Randomized trials needed to determine cause and effect
Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”
The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.
“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.
And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”
James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.
“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.
Opposite effects of sulfonylureas, TZDs versus metformin
The study authors analyzed 559,106 VA patients with type 2 diabetes who initiated glucose-lowering medication during 2001-2017 and took it for at least a year. They were aged 60 years or older and did not have dementia at baseline. Most were White (76.8%) and male (96.9%), two-thirds (63.1%) had obesity, and mean hemoglobin A1c was 6.8%.
Overall, 31,125 developed all-cause dementia. The incidence rate was 8.2 cases per 1,000 person-years, ranging from 6.2 cases per 1,000 person-years among those taking metformin monotherapy to 13.4 cases per 1,000 person-years in those taking both sulfonylurea and a TZD.
Compared with metformin monotherapy, the hazard ratio for all-cause dementia for sulfonylurea monotherapy was a significant 1.12. The increased risk was also seen for vascular dementia, with an HR of 1.14.
In contrast, TZD monotherapy was associated with a significantly lower risk for all-cause dementia (HR, 0.78), as well as for Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.
The combination of metformin and TZD also lowered the risk of all-cause dementia, while regimens including sulfonylureas raised the risks for all-cause and vascular dementia.
Most of the results didn’t change significantly when the drug exposure window was extended to 2 years.
Effects more pronounced in those with obesity
The protective 1-year effects of TZD monotherapy and of metformin plus TZD, compared with metformin alone, were more significant among participants aged 75 or younger and with a body mass index above 25 kg/m2, compared with those who were older than 75 years and with normal BMIs, respectively.
On the other hand, the greater risk for dementia incurred with sulfonylureas was further increased among those with higher BMI.
This research was partially funded by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute. Dr. Koychev is chief investigator for a trial, sponsored by Oxford University and funded by Novo Nordisk, testing whether the GLP-1 agonist semaglutide reduces the risk for dementia in aging adults.
A version of this article first appeared on Medscape.com.
a new observational study in patients with type 2 diabetes suggests.
The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.
“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.
The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.
“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
Randomized trials needed to determine cause and effect
Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”
The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.
“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.
And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”
James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.
“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.
Opposite effects of sulfonylureas, TZDs versus metformin
The study authors analyzed 559,106 VA patients with type 2 diabetes who initiated glucose-lowering medication during 2001-2017 and took it for at least a year. They were aged 60 years or older and did not have dementia at baseline. Most were White (76.8%) and male (96.9%), two-thirds (63.1%) had obesity, and mean hemoglobin A1c was 6.8%.
Overall, 31,125 developed all-cause dementia. The incidence rate was 8.2 cases per 1,000 person-years, ranging from 6.2 cases per 1,000 person-years among those taking metformin monotherapy to 13.4 cases per 1,000 person-years in those taking both sulfonylurea and a TZD.
Compared with metformin monotherapy, the hazard ratio for all-cause dementia for sulfonylurea monotherapy was a significant 1.12. The increased risk was also seen for vascular dementia, with an HR of 1.14.
In contrast, TZD monotherapy was associated with a significantly lower risk for all-cause dementia (HR, 0.78), as well as for Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.
The combination of metformin and TZD also lowered the risk of all-cause dementia, while regimens including sulfonylureas raised the risks for all-cause and vascular dementia.
Most of the results didn’t change significantly when the drug exposure window was extended to 2 years.
Effects more pronounced in those with obesity
The protective 1-year effects of TZD monotherapy and of metformin plus TZD, compared with metformin alone, were more significant among participants aged 75 or younger and with a body mass index above 25 kg/m2, compared with those who were older than 75 years and with normal BMIs, respectively.
On the other hand, the greater risk for dementia incurred with sulfonylureas was further increased among those with higher BMI.
This research was partially funded by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute. Dr. Koychev is chief investigator for a trial, sponsored by Oxford University and funded by Novo Nordisk, testing whether the GLP-1 agonist semaglutide reduces the risk for dementia in aging adults.
A version of this article first appeared on Medscape.com.
a new observational study in patients with type 2 diabetes suggests.
The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.
“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.
The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.
“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
Randomized trials needed to determine cause and effect
Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”
The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.
“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.
And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”
James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.
“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.
Opposite effects of sulfonylureas, TZDs versus metformin
The study authors analyzed 559,106 VA patients with type 2 diabetes who initiated glucose-lowering medication during 2001-2017 and took it for at least a year. They were aged 60 years or older and did not have dementia at baseline. Most were White (76.8%) and male (96.9%), two-thirds (63.1%) had obesity, and mean hemoglobin A1c was 6.8%.
Overall, 31,125 developed all-cause dementia. The incidence rate was 8.2 cases per 1,000 person-years, ranging from 6.2 cases per 1,000 person-years among those taking metformin monotherapy to 13.4 cases per 1,000 person-years in those taking both sulfonylurea and a TZD.
Compared with metformin monotherapy, the hazard ratio for all-cause dementia for sulfonylurea monotherapy was a significant 1.12. The increased risk was also seen for vascular dementia, with an HR of 1.14.
In contrast, TZD monotherapy was associated with a significantly lower risk for all-cause dementia (HR, 0.78), as well as for Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.
The combination of metformin and TZD also lowered the risk of all-cause dementia, while regimens including sulfonylureas raised the risks for all-cause and vascular dementia.
Most of the results didn’t change significantly when the drug exposure window was extended to 2 years.
Effects more pronounced in those with obesity
The protective 1-year effects of TZD monotherapy and of metformin plus TZD, compared with metformin alone, were more significant among participants aged 75 or younger and with a body mass index above 25 kg/m2, compared with those who were older than 75 years and with normal BMIs, respectively.
On the other hand, the greater risk for dementia incurred with sulfonylureas was further increased among those with higher BMI.
This research was partially funded by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute. Dr. Koychev is chief investigator for a trial, sponsored by Oxford University and funded by Novo Nordisk, testing whether the GLP-1 agonist semaglutide reduces the risk for dementia in aging adults.
A version of this article first appeared on Medscape.com.
FROM BMJ OPEN DIABETES RESEARCH & CARE
New advice on artificial pancreas insulin delivery systems
A new consensus statement summarizes the benefits, limitations, and challenges of using automated insulin delivery (AID) systems and provides recommendations for use by people with diabetes.
“Automated insulin delivery systems” is becoming the standard terminology – including by the U.S. Food and Drug Administration – to refer to systems that integrate data from a continuous glucose monitoring (CGM) system via a control algorithm into an insulin pump in order to automate subcutaneous insulin delivery. “Hybrid AID” or “hybrid closed-loop” refers to the current status of these systems, which still require some degree of user input to control glucose levels.
The term “artificial pancreas” was used interchangeably with AID in the past, but it doesn’t take into account exocrine pancreatic function. The term “bionic pancreas” refers to a specific system in development that would ultimately include glucagon along with insulin.
The new consensus report, titled “Automated insulin delivery: Benefits, challenges, and recommendations,” was published online in Diabetes Care and Diabetologia.
The document is geared toward not only diabetologists and other specialists, but also diabetes nurses and specialist dietitians. Colleagues working at regulatory agencies, health care organizations, and related media might also benefit from reading it.
It is endorsed by two professional societies – the European Association for the Study of Diabetes and the American Diabetes Association – and contrasts with other statements about AID systems that are sponsored by their manufacturers, noted document co-author Mark Evans, PhD, professor of diabetic medicine, University of Cambridge, England, in a statement.
“Many clinically relevant aspects, including safety, are addressed in this report. The aim ... is to encourage ongoing improvement of this technology, its safe and effective use, and its accessibility to all who can benefit from it,” Dr. Evans said.
Lead author Jennifer Sherr, MD, PhD, pediatric endocrinology, Yale University, New Haven, Conn., commented that the report “addresses the clinical usage of AID systems from a practical point of view rather than as ... a meta-analysis or a review of all relevant clinical studies. ... As such, the benefits and limitations of systems are discussed while also considering safety, regulatory pathways, and access to this technology.”
AID systems do not mean diabetes is “cured”
Separate recommendations provided at the end of the document are aimed at specific stakeholders, including health care providers, patients and their caregivers, manufacturers, regulatory agencies, and the research community.
The authors make clear in the introduction that, while representing “a significant movement toward optimizing glucose management for individuals with diabetes,” the use of AID systems doesn’t mean that diabetes is “cured.” Rather, “expectations need to be set adequately so that individuals with diabetes and providers understand what such systems can and cannot do.”
In particular, current commercially available AID systems require user input for mealtime insulin dosing and sometimes for correction doses of high blood glucose levels, although the systems at least partially automate that.
“When integrated into care, AID systems hold promise to relieve some of the daily burdens of diabetes care,” the authors write.
The statement also details problems that may arise with the physical devices, including skin irritation from adhesives, occlusion of insulin infusion sets, early CGM sensor failure, and inadequate dosing algorithms.
“Individuals with diabetes who are considering this type of advanced diabetes therapy should not only have appropriate technical understanding of the system but also be able to revert to standard diabetes treatment (that is, nonautomated subcutaneous insulin delivery by pump or injections) in case the AID system fails. They should be able to independently troubleshoot and have access to their health care provider if needed.”
To monitor the impact of the technology, the authors emphasize the importance of the time-in-range metric derived from CGM, with the goal of achieving 70% or greater time in target blood glucose range.
Separate sections of the document address the benefits and limitations of AID systems, education and expectations for both patients and providers, and patient and provider perspectives, including how to handle urgent questions.
Other sections cover special populations such as pregnant women and people with type 2 diabetes, considerations for patient selection for current AID systems, safety, improving access to the technology, liability, and do-it-yourself systems.
Recommendations for health care professionals
A table near the end of the document provides specific recommendations for health care professionals, including the following:
- Be knowledgeable about AID systems and nuances of different systems, including their distinguishing features as well as strengths and weaknesses.
- Inform patients with diabetes about AID systems, including review of currently available systems, and create realistic expectations for device use.
- Involve patients with diabetes in shared decision-making when considering use of AID systems.
- Share information with patients with diabetes, as well as their peers, about general standards set by national and international guidelines on AID systems.
- Provide an on-call number or method by which a person with diabetes can always access support from a health care provider at the practice, including weekends and nights.
- Implement, potentially, protocols on times when AID systems should not be used.
- Use an individual’s health data to improve quality of care and health outcomes.
Most members of the ADA/EASD Diabetes Technology Working Group work with industry, but industry had no input on the project. Dr. Sherr has reported conducting clinical trials for Eli Lilly, Insulet, and Medtronic, and has received in-kind support for research studies from Dexcom and Medtronic. She has also reported consulting for Eli Lilly, Lexicon, Medtronic, and Sanofi, and being an advisory board member for Bigfoot Biomedical, Cecelia Health, Eli Lilly, Insulet, T1D Fund, and Vertex Pharmaceuticals. Dr. Evans has reported conducting clinical trials or research collaborations for, serving on advisory boards for, or receiving speakers fees or travel support from Medtronic, Roche, Abbott Diabetes Care, Dexcom, Novo Nordisk, Eli Lilly, Sanofi, Zucara Therapeutics, Pila Pharma, and AstraZeneca. The University of Cambridge has received salary support for Dr. Evans from the National Health Service.
A version of this article first appeared on Medscape.com.
A new consensus statement summarizes the benefits, limitations, and challenges of using automated insulin delivery (AID) systems and provides recommendations for use by people with diabetes.
“Automated insulin delivery systems” is becoming the standard terminology – including by the U.S. Food and Drug Administration – to refer to systems that integrate data from a continuous glucose monitoring (CGM) system via a control algorithm into an insulin pump in order to automate subcutaneous insulin delivery. “Hybrid AID” or “hybrid closed-loop” refers to the current status of these systems, which still require some degree of user input to control glucose levels.
The term “artificial pancreas” was used interchangeably with AID in the past, but it doesn’t take into account exocrine pancreatic function. The term “bionic pancreas” refers to a specific system in development that would ultimately include glucagon along with insulin.
The new consensus report, titled “Automated insulin delivery: Benefits, challenges, and recommendations,” was published online in Diabetes Care and Diabetologia.
The document is geared toward not only diabetologists and other specialists, but also diabetes nurses and specialist dietitians. Colleagues working at regulatory agencies, health care organizations, and related media might also benefit from reading it.
It is endorsed by two professional societies – the European Association for the Study of Diabetes and the American Diabetes Association – and contrasts with other statements about AID systems that are sponsored by their manufacturers, noted document co-author Mark Evans, PhD, professor of diabetic medicine, University of Cambridge, England, in a statement.
“Many clinically relevant aspects, including safety, are addressed in this report. The aim ... is to encourage ongoing improvement of this technology, its safe and effective use, and its accessibility to all who can benefit from it,” Dr. Evans said.
Lead author Jennifer Sherr, MD, PhD, pediatric endocrinology, Yale University, New Haven, Conn., commented that the report “addresses the clinical usage of AID systems from a practical point of view rather than as ... a meta-analysis or a review of all relevant clinical studies. ... As such, the benefits and limitations of systems are discussed while also considering safety, regulatory pathways, and access to this technology.”
AID systems do not mean diabetes is “cured”
Separate recommendations provided at the end of the document are aimed at specific stakeholders, including health care providers, patients and their caregivers, manufacturers, regulatory agencies, and the research community.
The authors make clear in the introduction that, while representing “a significant movement toward optimizing glucose management for individuals with diabetes,” the use of AID systems doesn’t mean that diabetes is “cured.” Rather, “expectations need to be set adequately so that individuals with diabetes and providers understand what such systems can and cannot do.”
In particular, current commercially available AID systems require user input for mealtime insulin dosing and sometimes for correction doses of high blood glucose levels, although the systems at least partially automate that.
“When integrated into care, AID systems hold promise to relieve some of the daily burdens of diabetes care,” the authors write.
The statement also details problems that may arise with the physical devices, including skin irritation from adhesives, occlusion of insulin infusion sets, early CGM sensor failure, and inadequate dosing algorithms.
“Individuals with diabetes who are considering this type of advanced diabetes therapy should not only have appropriate technical understanding of the system but also be able to revert to standard diabetes treatment (that is, nonautomated subcutaneous insulin delivery by pump or injections) in case the AID system fails. They should be able to independently troubleshoot and have access to their health care provider if needed.”
To monitor the impact of the technology, the authors emphasize the importance of the time-in-range metric derived from CGM, with the goal of achieving 70% or greater time in target blood glucose range.
Separate sections of the document address the benefits and limitations of AID systems, education and expectations for both patients and providers, and patient and provider perspectives, including how to handle urgent questions.
Other sections cover special populations such as pregnant women and people with type 2 diabetes, considerations for patient selection for current AID systems, safety, improving access to the technology, liability, and do-it-yourself systems.
Recommendations for health care professionals
A table near the end of the document provides specific recommendations for health care professionals, including the following:
- Be knowledgeable about AID systems and nuances of different systems, including their distinguishing features as well as strengths and weaknesses.
- Inform patients with diabetes about AID systems, including review of currently available systems, and create realistic expectations for device use.
- Involve patients with diabetes in shared decision-making when considering use of AID systems.
- Share information with patients with diabetes, as well as their peers, about general standards set by national and international guidelines on AID systems.
- Provide an on-call number or method by which a person with diabetes can always access support from a health care provider at the practice, including weekends and nights.
- Implement, potentially, protocols on times when AID systems should not be used.
- Use an individual’s health data to improve quality of care and health outcomes.
Most members of the ADA/EASD Diabetes Technology Working Group work with industry, but industry had no input on the project. Dr. Sherr has reported conducting clinical trials for Eli Lilly, Insulet, and Medtronic, and has received in-kind support for research studies from Dexcom and Medtronic. She has also reported consulting for Eli Lilly, Lexicon, Medtronic, and Sanofi, and being an advisory board member for Bigfoot Biomedical, Cecelia Health, Eli Lilly, Insulet, T1D Fund, and Vertex Pharmaceuticals. Dr. Evans has reported conducting clinical trials or research collaborations for, serving on advisory boards for, or receiving speakers fees or travel support from Medtronic, Roche, Abbott Diabetes Care, Dexcom, Novo Nordisk, Eli Lilly, Sanofi, Zucara Therapeutics, Pila Pharma, and AstraZeneca. The University of Cambridge has received salary support for Dr. Evans from the National Health Service.
A version of this article first appeared on Medscape.com.
A new consensus statement summarizes the benefits, limitations, and challenges of using automated insulin delivery (AID) systems and provides recommendations for use by people with diabetes.
“Automated insulin delivery systems” is becoming the standard terminology – including by the U.S. Food and Drug Administration – to refer to systems that integrate data from a continuous glucose monitoring (CGM) system via a control algorithm into an insulin pump in order to automate subcutaneous insulin delivery. “Hybrid AID” or “hybrid closed-loop” refers to the current status of these systems, which still require some degree of user input to control glucose levels.
The term “artificial pancreas” was used interchangeably with AID in the past, but it doesn’t take into account exocrine pancreatic function. The term “bionic pancreas” refers to a specific system in development that would ultimately include glucagon along with insulin.
The new consensus report, titled “Automated insulin delivery: Benefits, challenges, and recommendations,” was published online in Diabetes Care and Diabetologia.
The document is geared toward not only diabetologists and other specialists, but also diabetes nurses and specialist dietitians. Colleagues working at regulatory agencies, health care organizations, and related media might also benefit from reading it.
It is endorsed by two professional societies – the European Association for the Study of Diabetes and the American Diabetes Association – and contrasts with other statements about AID systems that are sponsored by their manufacturers, noted document co-author Mark Evans, PhD, professor of diabetic medicine, University of Cambridge, England, in a statement.
“Many clinically relevant aspects, including safety, are addressed in this report. The aim ... is to encourage ongoing improvement of this technology, its safe and effective use, and its accessibility to all who can benefit from it,” Dr. Evans said.
Lead author Jennifer Sherr, MD, PhD, pediatric endocrinology, Yale University, New Haven, Conn., commented that the report “addresses the clinical usage of AID systems from a practical point of view rather than as ... a meta-analysis or a review of all relevant clinical studies. ... As such, the benefits and limitations of systems are discussed while also considering safety, regulatory pathways, and access to this technology.”
AID systems do not mean diabetes is “cured”
Separate recommendations provided at the end of the document are aimed at specific stakeholders, including health care providers, patients and their caregivers, manufacturers, regulatory agencies, and the research community.
The authors make clear in the introduction that, while representing “a significant movement toward optimizing glucose management for individuals with diabetes,” the use of AID systems doesn’t mean that diabetes is “cured.” Rather, “expectations need to be set adequately so that individuals with diabetes and providers understand what such systems can and cannot do.”
In particular, current commercially available AID systems require user input for mealtime insulin dosing and sometimes for correction doses of high blood glucose levels, although the systems at least partially automate that.
“When integrated into care, AID systems hold promise to relieve some of the daily burdens of diabetes care,” the authors write.
The statement also details problems that may arise with the physical devices, including skin irritation from adhesives, occlusion of insulin infusion sets, early CGM sensor failure, and inadequate dosing algorithms.
“Individuals with diabetes who are considering this type of advanced diabetes therapy should not only have appropriate technical understanding of the system but also be able to revert to standard diabetes treatment (that is, nonautomated subcutaneous insulin delivery by pump or injections) in case the AID system fails. They should be able to independently troubleshoot and have access to their health care provider if needed.”
To monitor the impact of the technology, the authors emphasize the importance of the time-in-range metric derived from CGM, with the goal of achieving 70% or greater time in target blood glucose range.
Separate sections of the document address the benefits and limitations of AID systems, education and expectations for both patients and providers, and patient and provider perspectives, including how to handle urgent questions.
Other sections cover special populations such as pregnant women and people with type 2 diabetes, considerations for patient selection for current AID systems, safety, improving access to the technology, liability, and do-it-yourself systems.
Recommendations for health care professionals
A table near the end of the document provides specific recommendations for health care professionals, including the following:
- Be knowledgeable about AID systems and nuances of different systems, including their distinguishing features as well as strengths and weaknesses.
- Inform patients with diabetes about AID systems, including review of currently available systems, and create realistic expectations for device use.
- Involve patients with diabetes in shared decision-making when considering use of AID systems.
- Share information with patients with diabetes, as well as their peers, about general standards set by national and international guidelines on AID systems.
- Provide an on-call number or method by which a person with diabetes can always access support from a health care provider at the practice, including weekends and nights.
- Implement, potentially, protocols on times when AID systems should not be used.
- Use an individual’s health data to improve quality of care and health outcomes.
Most members of the ADA/EASD Diabetes Technology Working Group work with industry, but industry had no input on the project. Dr. Sherr has reported conducting clinical trials for Eli Lilly, Insulet, and Medtronic, and has received in-kind support for research studies from Dexcom and Medtronic. She has also reported consulting for Eli Lilly, Lexicon, Medtronic, and Sanofi, and being an advisory board member for Bigfoot Biomedical, Cecelia Health, Eli Lilly, Insulet, T1D Fund, and Vertex Pharmaceuticals. Dr. Evans has reported conducting clinical trials or research collaborations for, serving on advisory boards for, or receiving speakers fees or travel support from Medtronic, Roche, Abbott Diabetes Care, Dexcom, Novo Nordisk, Eli Lilly, Sanofi, Zucara Therapeutics, Pila Pharma, and AstraZeneca. The University of Cambridge has received salary support for Dr. Evans from the National Health Service.
A version of this article first appeared on Medscape.com.
FROM DIABETES CARE AND DIABETOLOGIA
Strong link found between enterovirus and type 1 diabetes
STOCKHOLM – Enterovirus infection appears to be strongly linked to both type 1 diabetes and islet cell autoantibodies, new research suggests.
The strength of the relationship, particularly within the first month of type 1 diabetes diagnosis, “further supports the rationale for development of enterovirus-targeted vaccines and antiviral therapy to prevent and reduce the impact of type 1 diabetes,” according to lead investigator Sonia Isaacs, MD, of the department of pediatrics and child health at the University of New South Wales, Sydney, Australia.
Enteroviruses are a large family of viruses responsible for many infections in children. These live in the intestinal tract but can cause a wide variety of illnesses. There are more than 70 different strains, which include the group A and group B coxsackieviruses, the polioviruses, hepatitis A virus, and several strains that just go by the name enterovirus.
Dr. Isaacs presented the data, from a meta-analysis of studies using modern molecular techniques, at the annual meeting of the European Association for the Study of Diabetes.
The findings raise the question of whether people should be routinely tested for enterovirus at the time of type 1 diabetes diagnosis, she said during her presentation.
Asked by this news organization about the implications for first-degree relatives of people with type 1 diabetes, Dr. Isaacs said that they are “definitely a population to watch out for,” with regard to enteroviral infections. “Type 1 diabetes is very diverse and has different endotypes. Different environmental factors may be implicated in these different endotypes, and it may be that the enteroviruses are quite important in the first-degree relative group.”
Asked to comment, session moderator Kamlesh Khunti, MD, PhD, told this news organization that the data were “compelling,” particularly in the short term after type 1 diabetes diagnosis. “It seems that there may be plausibility for enterovirus associated with the development of type 1 diabetes ... Are there methods by which we can reduce this risk with either antivirals or vaccinations? I think that needs to be tested.”
And in regard to first-degree relatives, “I think that’s the group to go for because the association is so highly correlated. I think that’s the group worth testing with any interventions,” said Dr. Khunti, professor of primary care diabetes and vascular medicine at the University of Leicester, England.
Link stronger a month after diagnosis, in close relatives, in Europe
The new meta-analysis is an update to a prior review published in 2011 by Dr. Isaacs’ group, which found that people with islet cell autoimmunity were more than four times as likely as were controls to have an enterovirus infection, and people with type 1 diabetes were almost 10 times as likely.
This new analysis focuses on studies using more modern molecular techniques for detecting viruses, including high throughput sequencing and single-cell technologies.
The analysis identified 60 studies with a total of 12,077 participants, of whom 900 had islet autoimmunity, 5,081 had type 1 diabetes, and 6,096 were controls. Thirty-five of the studies were from Europe, while others were from the United States, Asia, and the Middle East.
Of 16 studies examining enterovirus infection in islet autoimmunity, cases with islet autoimmunity were twice as likely to have an enterovirus infection at any time point compared to controls, a significant difference (odds ratio [OR], 2.07, P = .002.)
Among 48 studies reporting enterovirus infection in type 1 diabetes, those with type 1 diabetes were eight times as likely to have an enterovirus infection compared with controls (OR, 8.0, P < .00001).
In 25 studies including 2,977 participants with onset of type 1 diabetes within the prior month, those individuals were more than 16 times more likely to present with an enterovirus infection (OR, 16.2, P < .00001).
“The strength of this is association is greater than previously reported by both us and others,” Dr. Isaacs noted.
The association between enterovirus infection and islet autoimmunity was greater in individuals who later progressed to type 1 diabetes, with odds ratio 5.1 vs. 2.0 for those who didn’t. The association was most evident at or shortly after seroconversion (5.1), was stronger in Europe (3.2) than in other regions (1.9), and was stronger among those with a first-degree relative with type 1 diabetes (9.8) than those recruited via a high-risk human leukocyte antigen (HLA), in whom the relationship wasn’t significant.
Having multiple or consecutive enteroviral infections was also associated with islet autoimmunity (2.0).
With type 1 diabetes, the relationship with enterovirus was greater in children (9.0) than in adults (4.1), and was greater for type 1 diabetes onset within 1 year (13.8) and within 1 month (16.2) than for those with established type 1 diabetes (7.0). Here, too, the relationship was stronger in Europe (10.2) than outside Europe (7.5).
The link with type 1 diabetes and enterovirus was particularly strong for those with both a first-degree relative and a high-risk HLA (141.4).
The relationship with type 1 diabetes was significant for enterovirus species A (3.7), B (12.7) and C (13.8), including coxsackie virus genotypes, but not D.
“Future studies should focus on characterizing enterovirus genomes in at-risk cohorts rather than just the presence or absence of the virus,” Dr. Isaacs said.
However, she added, “type 1 diabetes is such a heterogenous condition, viruses may be implicated more in one type than another. It’s important that we start to look into this.”
Dr. Isaacs reports no relevant financial relationships. Dr. Khunti disclosed ties with AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG / Menarini Group, Janssen, and Napp.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Enterovirus infection appears to be strongly linked to both type 1 diabetes and islet cell autoantibodies, new research suggests.
The strength of the relationship, particularly within the first month of type 1 diabetes diagnosis, “further supports the rationale for development of enterovirus-targeted vaccines and antiviral therapy to prevent and reduce the impact of type 1 diabetes,” according to lead investigator Sonia Isaacs, MD, of the department of pediatrics and child health at the University of New South Wales, Sydney, Australia.
Enteroviruses are a large family of viruses responsible for many infections in children. These live in the intestinal tract but can cause a wide variety of illnesses. There are more than 70 different strains, which include the group A and group B coxsackieviruses, the polioviruses, hepatitis A virus, and several strains that just go by the name enterovirus.
Dr. Isaacs presented the data, from a meta-analysis of studies using modern molecular techniques, at the annual meeting of the European Association for the Study of Diabetes.
The findings raise the question of whether people should be routinely tested for enterovirus at the time of type 1 diabetes diagnosis, she said during her presentation.
Asked by this news organization about the implications for first-degree relatives of people with type 1 diabetes, Dr. Isaacs said that they are “definitely a population to watch out for,” with regard to enteroviral infections. “Type 1 diabetes is very diverse and has different endotypes. Different environmental factors may be implicated in these different endotypes, and it may be that the enteroviruses are quite important in the first-degree relative group.”
Asked to comment, session moderator Kamlesh Khunti, MD, PhD, told this news organization that the data were “compelling,” particularly in the short term after type 1 diabetes diagnosis. “It seems that there may be plausibility for enterovirus associated with the development of type 1 diabetes ... Are there methods by which we can reduce this risk with either antivirals or vaccinations? I think that needs to be tested.”
And in regard to first-degree relatives, “I think that’s the group to go for because the association is so highly correlated. I think that’s the group worth testing with any interventions,” said Dr. Khunti, professor of primary care diabetes and vascular medicine at the University of Leicester, England.
Link stronger a month after diagnosis, in close relatives, in Europe
The new meta-analysis is an update to a prior review published in 2011 by Dr. Isaacs’ group, which found that people with islet cell autoimmunity were more than four times as likely as were controls to have an enterovirus infection, and people with type 1 diabetes were almost 10 times as likely.
This new analysis focuses on studies using more modern molecular techniques for detecting viruses, including high throughput sequencing and single-cell technologies.
The analysis identified 60 studies with a total of 12,077 participants, of whom 900 had islet autoimmunity, 5,081 had type 1 diabetes, and 6,096 were controls. Thirty-five of the studies were from Europe, while others were from the United States, Asia, and the Middle East.
Of 16 studies examining enterovirus infection in islet autoimmunity, cases with islet autoimmunity were twice as likely to have an enterovirus infection at any time point compared to controls, a significant difference (odds ratio [OR], 2.07, P = .002.)
Among 48 studies reporting enterovirus infection in type 1 diabetes, those with type 1 diabetes were eight times as likely to have an enterovirus infection compared with controls (OR, 8.0, P < .00001).
In 25 studies including 2,977 participants with onset of type 1 diabetes within the prior month, those individuals were more than 16 times more likely to present with an enterovirus infection (OR, 16.2, P < .00001).
“The strength of this is association is greater than previously reported by both us and others,” Dr. Isaacs noted.
The association between enterovirus infection and islet autoimmunity was greater in individuals who later progressed to type 1 diabetes, with odds ratio 5.1 vs. 2.0 for those who didn’t. The association was most evident at or shortly after seroconversion (5.1), was stronger in Europe (3.2) than in other regions (1.9), and was stronger among those with a first-degree relative with type 1 diabetes (9.8) than those recruited via a high-risk human leukocyte antigen (HLA), in whom the relationship wasn’t significant.
Having multiple or consecutive enteroviral infections was also associated with islet autoimmunity (2.0).
With type 1 diabetes, the relationship with enterovirus was greater in children (9.0) than in adults (4.1), and was greater for type 1 diabetes onset within 1 year (13.8) and within 1 month (16.2) than for those with established type 1 diabetes (7.0). Here, too, the relationship was stronger in Europe (10.2) than outside Europe (7.5).
The link with type 1 diabetes and enterovirus was particularly strong for those with both a first-degree relative and a high-risk HLA (141.4).
The relationship with type 1 diabetes was significant for enterovirus species A (3.7), B (12.7) and C (13.8), including coxsackie virus genotypes, but not D.
“Future studies should focus on characterizing enterovirus genomes in at-risk cohorts rather than just the presence or absence of the virus,” Dr. Isaacs said.
However, she added, “type 1 diabetes is such a heterogenous condition, viruses may be implicated more in one type than another. It’s important that we start to look into this.”
Dr. Isaacs reports no relevant financial relationships. Dr. Khunti disclosed ties with AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG / Menarini Group, Janssen, and Napp.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Enterovirus infection appears to be strongly linked to both type 1 diabetes and islet cell autoantibodies, new research suggests.
The strength of the relationship, particularly within the first month of type 1 diabetes diagnosis, “further supports the rationale for development of enterovirus-targeted vaccines and antiviral therapy to prevent and reduce the impact of type 1 diabetes,” according to lead investigator Sonia Isaacs, MD, of the department of pediatrics and child health at the University of New South Wales, Sydney, Australia.
Enteroviruses are a large family of viruses responsible for many infections in children. These live in the intestinal tract but can cause a wide variety of illnesses. There are more than 70 different strains, which include the group A and group B coxsackieviruses, the polioviruses, hepatitis A virus, and several strains that just go by the name enterovirus.
Dr. Isaacs presented the data, from a meta-analysis of studies using modern molecular techniques, at the annual meeting of the European Association for the Study of Diabetes.
The findings raise the question of whether people should be routinely tested for enterovirus at the time of type 1 diabetes diagnosis, she said during her presentation.
Asked by this news organization about the implications for first-degree relatives of people with type 1 diabetes, Dr. Isaacs said that they are “definitely a population to watch out for,” with regard to enteroviral infections. “Type 1 diabetes is very diverse and has different endotypes. Different environmental factors may be implicated in these different endotypes, and it may be that the enteroviruses are quite important in the first-degree relative group.”
Asked to comment, session moderator Kamlesh Khunti, MD, PhD, told this news organization that the data were “compelling,” particularly in the short term after type 1 diabetes diagnosis. “It seems that there may be plausibility for enterovirus associated with the development of type 1 diabetes ... Are there methods by which we can reduce this risk with either antivirals or vaccinations? I think that needs to be tested.”
And in regard to first-degree relatives, “I think that’s the group to go for because the association is so highly correlated. I think that’s the group worth testing with any interventions,” said Dr. Khunti, professor of primary care diabetes and vascular medicine at the University of Leicester, England.
Link stronger a month after diagnosis, in close relatives, in Europe
The new meta-analysis is an update to a prior review published in 2011 by Dr. Isaacs’ group, which found that people with islet cell autoimmunity were more than four times as likely as were controls to have an enterovirus infection, and people with type 1 diabetes were almost 10 times as likely.
This new analysis focuses on studies using more modern molecular techniques for detecting viruses, including high throughput sequencing and single-cell technologies.
The analysis identified 60 studies with a total of 12,077 participants, of whom 900 had islet autoimmunity, 5,081 had type 1 diabetes, and 6,096 were controls. Thirty-five of the studies were from Europe, while others were from the United States, Asia, and the Middle East.
Of 16 studies examining enterovirus infection in islet autoimmunity, cases with islet autoimmunity were twice as likely to have an enterovirus infection at any time point compared to controls, a significant difference (odds ratio [OR], 2.07, P = .002.)
Among 48 studies reporting enterovirus infection in type 1 diabetes, those with type 1 diabetes were eight times as likely to have an enterovirus infection compared with controls (OR, 8.0, P < .00001).
In 25 studies including 2,977 participants with onset of type 1 diabetes within the prior month, those individuals were more than 16 times more likely to present with an enterovirus infection (OR, 16.2, P < .00001).
“The strength of this is association is greater than previously reported by both us and others,” Dr. Isaacs noted.
The association between enterovirus infection and islet autoimmunity was greater in individuals who later progressed to type 1 diabetes, with odds ratio 5.1 vs. 2.0 for those who didn’t. The association was most evident at or shortly after seroconversion (5.1), was stronger in Europe (3.2) than in other regions (1.9), and was stronger among those with a first-degree relative with type 1 diabetes (9.8) than those recruited via a high-risk human leukocyte antigen (HLA), in whom the relationship wasn’t significant.
Having multiple or consecutive enteroviral infections was also associated with islet autoimmunity (2.0).
With type 1 diabetes, the relationship with enterovirus was greater in children (9.0) than in adults (4.1), and was greater for type 1 diabetes onset within 1 year (13.8) and within 1 month (16.2) than for those with established type 1 diabetes (7.0). Here, too, the relationship was stronger in Europe (10.2) than outside Europe (7.5).
The link with type 1 diabetes and enterovirus was particularly strong for those with both a first-degree relative and a high-risk HLA (141.4).
The relationship with type 1 diabetes was significant for enterovirus species A (3.7), B (12.7) and C (13.8), including coxsackie virus genotypes, but not D.
“Future studies should focus on characterizing enterovirus genomes in at-risk cohorts rather than just the presence or absence of the virus,” Dr. Isaacs said.
However, she added, “type 1 diabetes is such a heterogenous condition, viruses may be implicated more in one type than another. It’s important that we start to look into this.”
Dr. Isaacs reports no relevant financial relationships. Dr. Khunti disclosed ties with AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG / Menarini Group, Janssen, and Napp.
A version of this article first appeared on Medscape.com.
AT EASD 2022