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Liver grafts donated after circulatory death increase early risk of diabetes
SAN FRANCISCO – The type of liver graft used in transplantation plays a large role in early development of new-onset diabetes, according to a retrospective study of 430 patients from the United Kingdom.
A team led by Dr. Hermien Hartog, an honorary clinical fellow in the Liver Unit, Queen Elizabeth Hospital, Birmingham, England, studied patients undergoing primary liver transplant between 2008 and 2012. Patients were excluded from the study if they had preexisting diabetes, had died, or had undergone retransplantation within 90 days.
The investigators assessed both the development of new-onset diabetes after transplant (NODAT), using criteria adapted from a published article (Transplantation 2013;96:58-64), and its resolution, defined as the date of cessation of antihyperglycemic therapy or the last episode of hyperglycemia.
Seventy-nine percent of the patients received grafts donated after brain death (DBD), Dr. Hartog reported at the annual meeting of the 2014 World Transplant Congress. Among the recipients of grafts donated after circulatory death (DCD), the mean warm ischemic time was 21 minutes.
With a median follow-up of 2.5 years, the cumulative 1-year incidence of NODAT was 19% in the entire cohort, with a median time to onset of 30 days. In the 44% of affected patients whose NODAT resolved, the median time to resolution was 150 days post transplantation, Dr. Hartog reported at the congress, which was sponsored by the American Society of Transplant Surgeons.
The cumulative 1-year incidence of NODAT was 23% in DCD graft recipients and 18% in DBD graft recipients, a nonsignificant difference. But when patients were stratified by graft type, "we saw an early occurrence and high peak incidence of NODAT in DCD graft recipients. Also, a larger proportion of these patients resolved their NODAT over time," she commented.
The overall temporal pattern suggested that "the effect that we see of graft type seems to be temporary and [lessens] over time when multifactorial factors come into play," according to Dr. Hartog.
In multivariate analyses, the risk of NODAT within 90 days of transplantation was higher for patients who received a DCD graft (hazard ratio, 1.8). More detailed analysis showed that the elevation of risk was greatest within the first 15 days.
"Our study confirms known associations with NODAT after liver transplantation but identifies DCD graft as a novel risk factor. This causes a temporary effect in the early post-transplant period that is independent from known risk factors," Dr. Hartog commented.
"Based on our observations, we hypothesize that hyperglycemia may be related to liver graft function through ischemia-reperfusion–induced hepatic insulin resistance," she added. "We are currently trying to confirm our data in an independent data set, which will also include postreperfusion glucose levels and correlation with the insulin receptor pathway in time-zero liver biopsies."
"The clinical relevance of our findings is as yet unknown," she acknowledged. However, they may help inform new approaches for graft optimization and selection.
Session cochair Dr. Darius Mirza, also of the University of Birmingham, asked, "Why does the pattern of recovery seem to be different in the DCDs versus the DBDs? Also, why are the cumulative incidence and the time frame so different?"
"Actually, in the literature, I have not seen any reports looking at the early post-transplant period. So most reports look at one time point, normally 1 year," Dr. Hartog replied. "What I think is that there is an early peak caused by DCD grafts that would explain why there is an early peak, but also why those patients recover later on. I think this peak is a bit obscure because there are also other factors that come into play, maybe after a while, that will obscure that first peak. If you would take those other factors out of the equation, I think you would just see a peak in the early period."
Dr. Mirza also wondered about the role of using DCD grafts that are accepted under extended criteria. "So you start off using mainly young, fit DCD livers. Now, the vast majority are extended-criteria DCD livers. Do you think that plays a role, or is it too early to say?"
"Yes, I think so," Dr. Hartog said, while adding that this phenomenon is likely not restricted to DCD grafts. "From earlier literature, there is a clear difference between a living donated graft and deceased donation. And it might also be that the extended grafts or the more steatotic grafts may exhibit this effect more than the better grafts."
Dr. Hartog disclosed no conflicts of interest relevant to the research.
SAN FRANCISCO – The type of liver graft used in transplantation plays a large role in early development of new-onset diabetes, according to a retrospective study of 430 patients from the United Kingdom.
A team led by Dr. Hermien Hartog, an honorary clinical fellow in the Liver Unit, Queen Elizabeth Hospital, Birmingham, England, studied patients undergoing primary liver transplant between 2008 and 2012. Patients were excluded from the study if they had preexisting diabetes, had died, or had undergone retransplantation within 90 days.
The investigators assessed both the development of new-onset diabetes after transplant (NODAT), using criteria adapted from a published article (Transplantation 2013;96:58-64), and its resolution, defined as the date of cessation of antihyperglycemic therapy or the last episode of hyperglycemia.
Seventy-nine percent of the patients received grafts donated after brain death (DBD), Dr. Hartog reported at the annual meeting of the 2014 World Transplant Congress. Among the recipients of grafts donated after circulatory death (DCD), the mean warm ischemic time was 21 minutes.
With a median follow-up of 2.5 years, the cumulative 1-year incidence of NODAT was 19% in the entire cohort, with a median time to onset of 30 days. In the 44% of affected patients whose NODAT resolved, the median time to resolution was 150 days post transplantation, Dr. Hartog reported at the congress, which was sponsored by the American Society of Transplant Surgeons.
The cumulative 1-year incidence of NODAT was 23% in DCD graft recipients and 18% in DBD graft recipients, a nonsignificant difference. But when patients were stratified by graft type, "we saw an early occurrence and high peak incidence of NODAT in DCD graft recipients. Also, a larger proportion of these patients resolved their NODAT over time," she commented.
The overall temporal pattern suggested that "the effect that we see of graft type seems to be temporary and [lessens] over time when multifactorial factors come into play," according to Dr. Hartog.
In multivariate analyses, the risk of NODAT within 90 days of transplantation was higher for patients who received a DCD graft (hazard ratio, 1.8). More detailed analysis showed that the elevation of risk was greatest within the first 15 days.
"Our study confirms known associations with NODAT after liver transplantation but identifies DCD graft as a novel risk factor. This causes a temporary effect in the early post-transplant period that is independent from known risk factors," Dr. Hartog commented.
"Based on our observations, we hypothesize that hyperglycemia may be related to liver graft function through ischemia-reperfusion–induced hepatic insulin resistance," she added. "We are currently trying to confirm our data in an independent data set, which will also include postreperfusion glucose levels and correlation with the insulin receptor pathway in time-zero liver biopsies."
"The clinical relevance of our findings is as yet unknown," she acknowledged. However, they may help inform new approaches for graft optimization and selection.
Session cochair Dr. Darius Mirza, also of the University of Birmingham, asked, "Why does the pattern of recovery seem to be different in the DCDs versus the DBDs? Also, why are the cumulative incidence and the time frame so different?"
"Actually, in the literature, I have not seen any reports looking at the early post-transplant period. So most reports look at one time point, normally 1 year," Dr. Hartog replied. "What I think is that there is an early peak caused by DCD grafts that would explain why there is an early peak, but also why those patients recover later on. I think this peak is a bit obscure because there are also other factors that come into play, maybe after a while, that will obscure that first peak. If you would take those other factors out of the equation, I think you would just see a peak in the early period."
Dr. Mirza also wondered about the role of using DCD grafts that are accepted under extended criteria. "So you start off using mainly young, fit DCD livers. Now, the vast majority are extended-criteria DCD livers. Do you think that plays a role, or is it too early to say?"
"Yes, I think so," Dr. Hartog said, while adding that this phenomenon is likely not restricted to DCD grafts. "From earlier literature, there is a clear difference between a living donated graft and deceased donation. And it might also be that the extended grafts or the more steatotic grafts may exhibit this effect more than the better grafts."
Dr. Hartog disclosed no conflicts of interest relevant to the research.
SAN FRANCISCO – The type of liver graft used in transplantation plays a large role in early development of new-onset diabetes, according to a retrospective study of 430 patients from the United Kingdom.
A team led by Dr. Hermien Hartog, an honorary clinical fellow in the Liver Unit, Queen Elizabeth Hospital, Birmingham, England, studied patients undergoing primary liver transplant between 2008 and 2012. Patients were excluded from the study if they had preexisting diabetes, had died, or had undergone retransplantation within 90 days.
The investigators assessed both the development of new-onset diabetes after transplant (NODAT), using criteria adapted from a published article (Transplantation 2013;96:58-64), and its resolution, defined as the date of cessation of antihyperglycemic therapy or the last episode of hyperglycemia.
Seventy-nine percent of the patients received grafts donated after brain death (DBD), Dr. Hartog reported at the annual meeting of the 2014 World Transplant Congress. Among the recipients of grafts donated after circulatory death (DCD), the mean warm ischemic time was 21 minutes.
With a median follow-up of 2.5 years, the cumulative 1-year incidence of NODAT was 19% in the entire cohort, with a median time to onset of 30 days. In the 44% of affected patients whose NODAT resolved, the median time to resolution was 150 days post transplantation, Dr. Hartog reported at the congress, which was sponsored by the American Society of Transplant Surgeons.
The cumulative 1-year incidence of NODAT was 23% in DCD graft recipients and 18% in DBD graft recipients, a nonsignificant difference. But when patients were stratified by graft type, "we saw an early occurrence and high peak incidence of NODAT in DCD graft recipients. Also, a larger proportion of these patients resolved their NODAT over time," she commented.
The overall temporal pattern suggested that "the effect that we see of graft type seems to be temporary and [lessens] over time when multifactorial factors come into play," according to Dr. Hartog.
In multivariate analyses, the risk of NODAT within 90 days of transplantation was higher for patients who received a DCD graft (hazard ratio, 1.8). More detailed analysis showed that the elevation of risk was greatest within the first 15 days.
"Our study confirms known associations with NODAT after liver transplantation but identifies DCD graft as a novel risk factor. This causes a temporary effect in the early post-transplant period that is independent from known risk factors," Dr. Hartog commented.
"Based on our observations, we hypothesize that hyperglycemia may be related to liver graft function through ischemia-reperfusion–induced hepatic insulin resistance," she added. "We are currently trying to confirm our data in an independent data set, which will also include postreperfusion glucose levels and correlation with the insulin receptor pathway in time-zero liver biopsies."
"The clinical relevance of our findings is as yet unknown," she acknowledged. However, they may help inform new approaches for graft optimization and selection.
Session cochair Dr. Darius Mirza, also of the University of Birmingham, asked, "Why does the pattern of recovery seem to be different in the DCDs versus the DBDs? Also, why are the cumulative incidence and the time frame so different?"
"Actually, in the literature, I have not seen any reports looking at the early post-transplant period. So most reports look at one time point, normally 1 year," Dr. Hartog replied. "What I think is that there is an early peak caused by DCD grafts that would explain why there is an early peak, but also why those patients recover later on. I think this peak is a bit obscure because there are also other factors that come into play, maybe after a while, that will obscure that first peak. If you would take those other factors out of the equation, I think you would just see a peak in the early period."
Dr. Mirza also wondered about the role of using DCD grafts that are accepted under extended criteria. "So you start off using mainly young, fit DCD livers. Now, the vast majority are extended-criteria DCD livers. Do you think that plays a role, or is it too early to say?"
"Yes, I think so," Dr. Hartog said, while adding that this phenomenon is likely not restricted to DCD grafts. "From earlier literature, there is a clear difference between a living donated graft and deceased donation. And it might also be that the extended grafts or the more steatotic grafts may exhibit this effect more than the better grafts."
Dr. Hartog disclosed no conflicts of interest relevant to the research.
AT THE 2014 WORLD TRANSPLANT CONGRESS
Key clinical point: Recipients of liver grafts donated after circulatory death are at a slightly higher risk for post-transplant new-onset diabetes.
Major finding: The risk of new-onset diabetes within 90 days of transplantation was 1.8-fold higher for patients who received a DCD graft than for peers who received a DBD graft.
Data source: A retrospective cohort study of 430 primary liver transplant recipients
Disclosures: Dr. Hartog disclosed no relevant conflicts of interest.
Gestational diabetes may increase child’s risk of glucose intolerance
Obese children may have a higher risk of developing type 2 diabetes if their mothers had gestational diabetes during pregnancy, according to a recent study.
"The ever growing number of women with gestational diabetes (18%) suggests that the future will be filled with children with early diabetes at a rate that far exceeds the current prevalence," wrote Tara Holder of Yale University, New Haven, Conn., and her associates in Diabetologia.
"Offspring of GDM [gestational diabetes mellitus] mothers ought to be screened for impaired glucose tolerance and/or impaired fasting glucose, and preventive and therapeutic strategies should be considered before the development of full clinical manifestation of diabetes," the researchers reported online (Diabetologia 2014 Aug. 29 [doi: 10.1007/s00125-014-3345-2]).
The investigators conducted an oral glucose tolerance test to establish normal glucose tolerance among 210 obese teens who had not been exposed to GDM and 45 obese teens who had been exposed. Then they conducted another OGTT at an average follow-up of 2.8 years later.
A fasting glucose level of less than 5.55 mmol/L and a 2-hour glucose level of less than 7.77 mmol/L were defined as normal glucose tolerance. A fasting glucose of 5.55-6.88 mmol/L was considered impaired, and a fasting glucose greater than 6.88 mmol/ L or a 2-hour glucose greater than 11.05 mmol/L was designated type 2 diabetes.
At follow-up, 91.4% of the teens not exposed to GDM had normal glucose tolerance, compared with 68.9% of the teens exposed to GDM. Therefore, 8.6% of those not exposed to GDM and 31.1% of those exposed to GDM had developed either impaired glucose tolerance or type 2 diabetes.
The research and researchers were supported by the National Center for Advancing Translational Science, the Yale Diabetes Endocrinology Research Center, the European Society of Pediatric Endocrinology, the American Heart Association, the Stephen Morse Diabetes Research Foundation, the National Institutes of Health, and the American Diabetes Association. The authors had no disclosures.
The study by Holder et al. confirms previous findings that a child’s exposure to maternal GDM can predispose him or her to developing impaired glucose tolerance or type 2 diabetes later in life. Seminal work by David Pettitt and Peter Bennett, who studied the Pima Indians in Arizona, showed that a child born to a mother without GDM and a child born to the same mother with GDM had different susceptibilities to developing metabolic disease. They found that the child exposed to GDM had a higher likelihood of developing diabetes.
The findings of Holder et al. reinforce the idea that maternal health can greatly influence the long-term health of her offspring. It is conceivable that diabetes may "imprint" information onto the islet cells of the developing fetus, thereby resulting in the reduced beta-cell function and reduced insulin sensitivity observed by the investigators. Although it remains to be elucidated, it is not unlikely that there are diabetes susceptibility genes, which women may pass on to their offspring. If so, this could explain why only some children of GDM mothers develop impaired glucose tolerance or type 2 diabetes mellitus while others do not.
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Counseling children of diabetic mothers on the importance of a healthy lifestyle, maintaining an ideal weight, consuming a balanced diet, and getting enough physical exercise could reduce their risk of future metabolic disease. Because the exposure to maternal hyperglycemia cannot be reversed, it is vital that children of GDM mothers take steps needed to reduce their risks of developing diabetes.
Dr. E. Albert Reece, M.D., Ph.D., M.B.A., is the Vice President for Medical Affairs at the University of Maryland, Dean of the School of Medicine, and the John Z. and Akiko K. Bowers Distinguished Professor in Obstetrics and Gynecology. He made these comments in an interview. Dr. Reece had no relevant financial disclosures.
The study by Holder et al. confirms previous findings that a child’s exposure to maternal GDM can predispose him or her to developing impaired glucose tolerance or type 2 diabetes later in life. Seminal work by David Pettitt and Peter Bennett, who studied the Pima Indians in Arizona, showed that a child born to a mother without GDM and a child born to the same mother with GDM had different susceptibilities to developing metabolic disease. They found that the child exposed to GDM had a higher likelihood of developing diabetes.
The findings of Holder et al. reinforce the idea that maternal health can greatly influence the long-term health of her offspring. It is conceivable that diabetes may "imprint" information onto the islet cells of the developing fetus, thereby resulting in the reduced beta-cell function and reduced insulin sensitivity observed by the investigators. Although it remains to be elucidated, it is not unlikely that there are diabetes susceptibility genes, which women may pass on to their offspring. If so, this could explain why only some children of GDM mothers develop impaired glucose tolerance or type 2 diabetes mellitus while others do not.
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Counseling children of diabetic mothers on the importance of a healthy lifestyle, maintaining an ideal weight, consuming a balanced diet, and getting enough physical exercise could reduce their risk of future metabolic disease. Because the exposure to maternal hyperglycemia cannot be reversed, it is vital that children of GDM mothers take steps needed to reduce their risks of developing diabetes.
Dr. E. Albert Reece, M.D., Ph.D., M.B.A., is the Vice President for Medical Affairs at the University of Maryland, Dean of the School of Medicine, and the John Z. and Akiko K. Bowers Distinguished Professor in Obstetrics and Gynecology. He made these comments in an interview. Dr. Reece had no relevant financial disclosures.
The study by Holder et al. confirms previous findings that a child’s exposure to maternal GDM can predispose him or her to developing impaired glucose tolerance or type 2 diabetes later in life. Seminal work by David Pettitt and Peter Bennett, who studied the Pima Indians in Arizona, showed that a child born to a mother without GDM and a child born to the same mother with GDM had different susceptibilities to developing metabolic disease. They found that the child exposed to GDM had a higher likelihood of developing diabetes.
The findings of Holder et al. reinforce the idea that maternal health can greatly influence the long-term health of her offspring. It is conceivable that diabetes may "imprint" information onto the islet cells of the developing fetus, thereby resulting in the reduced beta-cell function and reduced insulin sensitivity observed by the investigators. Although it remains to be elucidated, it is not unlikely that there are diabetes susceptibility genes, which women may pass on to their offspring. If so, this could explain why only some children of GDM mothers develop impaired glucose tolerance or type 2 diabetes mellitus while others do not.
|
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Counseling children of diabetic mothers on the importance of a healthy lifestyle, maintaining an ideal weight, consuming a balanced diet, and getting enough physical exercise could reduce their risk of future metabolic disease. Because the exposure to maternal hyperglycemia cannot be reversed, it is vital that children of GDM mothers take steps needed to reduce their risks of developing diabetes.
Dr. E. Albert Reece, M.D., Ph.D., M.B.A., is the Vice President for Medical Affairs at the University of Maryland, Dean of the School of Medicine, and the John Z. and Akiko K. Bowers Distinguished Professor in Obstetrics and Gynecology. He made these comments in an interview. Dr. Reece had no relevant financial disclosures.
Obese children may have a higher risk of developing type 2 diabetes if their mothers had gestational diabetes during pregnancy, according to a recent study.
"The ever growing number of women with gestational diabetes (18%) suggests that the future will be filled with children with early diabetes at a rate that far exceeds the current prevalence," wrote Tara Holder of Yale University, New Haven, Conn., and her associates in Diabetologia.
"Offspring of GDM [gestational diabetes mellitus] mothers ought to be screened for impaired glucose tolerance and/or impaired fasting glucose, and preventive and therapeutic strategies should be considered before the development of full clinical manifestation of diabetes," the researchers reported online (Diabetologia 2014 Aug. 29 [doi: 10.1007/s00125-014-3345-2]).
The investigators conducted an oral glucose tolerance test to establish normal glucose tolerance among 210 obese teens who had not been exposed to GDM and 45 obese teens who had been exposed. Then they conducted another OGTT at an average follow-up of 2.8 years later.
A fasting glucose level of less than 5.55 mmol/L and a 2-hour glucose level of less than 7.77 mmol/L were defined as normal glucose tolerance. A fasting glucose of 5.55-6.88 mmol/L was considered impaired, and a fasting glucose greater than 6.88 mmol/ L or a 2-hour glucose greater than 11.05 mmol/L was designated type 2 diabetes.
At follow-up, 91.4% of the teens not exposed to GDM had normal glucose tolerance, compared with 68.9% of the teens exposed to GDM. Therefore, 8.6% of those not exposed to GDM and 31.1% of those exposed to GDM had developed either impaired glucose tolerance or type 2 diabetes.
The research and researchers were supported by the National Center for Advancing Translational Science, the Yale Diabetes Endocrinology Research Center, the European Society of Pediatric Endocrinology, the American Heart Association, the Stephen Morse Diabetes Research Foundation, the National Institutes of Health, and the American Diabetes Association. The authors had no disclosures.
Obese children may have a higher risk of developing type 2 diabetes if their mothers had gestational diabetes during pregnancy, according to a recent study.
"The ever growing number of women with gestational diabetes (18%) suggests that the future will be filled with children with early diabetes at a rate that far exceeds the current prevalence," wrote Tara Holder of Yale University, New Haven, Conn., and her associates in Diabetologia.
"Offspring of GDM [gestational diabetes mellitus] mothers ought to be screened for impaired glucose tolerance and/or impaired fasting glucose, and preventive and therapeutic strategies should be considered before the development of full clinical manifestation of diabetes," the researchers reported online (Diabetologia 2014 Aug. 29 [doi: 10.1007/s00125-014-3345-2]).
The investigators conducted an oral glucose tolerance test to establish normal glucose tolerance among 210 obese teens who had not been exposed to GDM and 45 obese teens who had been exposed. Then they conducted another OGTT at an average follow-up of 2.8 years later.
A fasting glucose level of less than 5.55 mmol/L and a 2-hour glucose level of less than 7.77 mmol/L were defined as normal glucose tolerance. A fasting glucose of 5.55-6.88 mmol/L was considered impaired, and a fasting glucose greater than 6.88 mmol/ L or a 2-hour glucose greater than 11.05 mmol/L was designated type 2 diabetes.
At follow-up, 91.4% of the teens not exposed to GDM had normal glucose tolerance, compared with 68.9% of the teens exposed to GDM. Therefore, 8.6% of those not exposed to GDM and 31.1% of those exposed to GDM had developed either impaired glucose tolerance or type 2 diabetes.
The research and researchers were supported by the National Center for Advancing Translational Science, the Yale Diabetes Endocrinology Research Center, the European Society of Pediatric Endocrinology, the American Heart Association, the Stephen Morse Diabetes Research Foundation, the National Institutes of Health, and the American Diabetes Association. The authors had no disclosures.
FROM DIABETOLOGIA
Key clinical point: Children whose mothers had gestational diabetes should be screened for impaired glucose tolerance and preventive strategies taught to forestall type 2 diabetes.
Major finding: A total of 31.1% of obese teens exposed to GDM had developed either impaired glucose tolerance or type 2 diabetes at follow-up, compared with 8.6% of those not exposed to GDM.
Data source: The findings are based on a cohort study of 255 obese adolescents followed for a mean 2.8 years.
Disclosures: The research and researchers were supported by the National Center for Advancing Translational Science, the Yale Diabetes Endocrinology Research Center, the European Society of Pediatric Endocrinology, the American Heart Association, the Stephen Morse Diabetes Research Foundation, the National Institutes of Health, and the American Diabetes Association. The authors had no disclosures.
Modest hypertension control in diabetic patients boosts survival
BARCELONA – A modest amount of blood pressure control over an average of 4 years produced a significant, long-term survival benefit in patients with type 2 diabetes, based on a 10-year follow-up of more than 8,000 patients.
"It is critically important to maintain active blood-pressure lowering in both the short and long term in order to derive the greatest possible reductions in mortality and major cardiovascular events" in patients with type 2 diabetes, Dr. John Chalmers said at the annual congress of the European Society of Cardiology.
The results he reported showed that during 10 years of total follow-up, 4 years of concerted therapy with a dual antihypertensive-drug formulation on top of background therapy produced an average drop in blood pressure of 5.6/2.2 mm Hg, which was linked to a relative 9% decrease in mortality through the entire 10-year period.
Dr. Chalmers’ analysis used data from an average 6-year follow-up of patients after they completed a 4-year trial that had randomized them to treatment with either the combined formulation of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide, or to placebo. The 6-year assessment of these patients after they finished the closely regulated treatment phase while in the clinical trial is "the longest follow-up on the impact of blood pressure reduction in patients with diabetes," commented Dr. Lars Rydén, a cardiologist at the Karolinska Institute in Stockholm.
"The greatest part of the overall, cumulative benefit [over a 10-year period] was contributed by the carry forward of the in-trial benefits of active BP lowering," said Dr. Chalmers, senior director of the George Institute for Global Health in Sydney, Australia.
His study focused on data collected from patients enrolled in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation) trial. This study randomized 11,140 patients with type 2 diabetes who were at least 55 years old and had at least one additional cardiovascular disease risk factor, to treatment with the combined formulation on top of their preexisting medications or to placebo plus existing medications (Lancet 2007;370:829-40). Patients in the placebo group were unable to receive an angiotensin-converting enzyme inhibitor during the study. The study was sponsored by Servier, the company that markets a combined perindopril and indapamide formulation (Preterax).
At enrollment, ADVANCE patients averaged 66 years old, had an average 8-year history of type 2 diabetes, and had an average blood pressure of 145/81 mm Hg. Three-quarters were on an antihypertensive regimen of some kind at entry into the study.
During the study’s 4 years of active treatment, patients randomized to receive the perindopril and indapamide combination had significantly reduced blood pressure, compared with the control patients. After 4 years, this linked to a 9% relative drop in the combined incidence of major macrovascular and microvascular events (including cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction). Compared with the control group, this cut in events was statistically significant for the study’s primary endpoint. The antihypertensive intervention also was linked to a statistically significant, 14% relative drop in all-cause deaths.
To assess the longer-term impact of this 4-year intervention, Dr. Chalmers and his associates ran a post-trial observational study, ADVANCE-ON. Initially, 8,494 of the patients who completed ADVANCE (83% of surviving patients) agreed to participate in ADVANCE-ON; after another 6 years of follow-up, 5,131 patients remained under observation. During the extended 6 years of follow-up, patients from both the initial intervention arm and the initial control arm all maintained average blood pressures of roughly 137/75 mm Hg. The blood pressures of the original intervention and control patient arms "fully converged," Dr. Chalmers said.
During this 6-year period, patients received care from their personal physicians and could receive any antihypertensive regimen their physician prescribed. At their first follow-up medical examination after the end of the main ADVANCE study, about 40% of patients were on no antihypertensive drugs, 23% were on one drug, 21% were on two drugs, and the remainder were on higher numbers of antihypertensive drugs.
During the 6-year post-trial period, patients who had previously been in the active-treatment arm had a 6% relative reduction in all-cause mortality, compared with patients originally in the control arm, a difference that was not significant.
But when the researchers combined the 6-year post-trial follow-up with the in-trial results for a total median 10-year follow-up, they found an overall 9% relative cut in mortality in the intervention patients, compared with the controls, and a relative 12% drop in cardiovascular mortality.
The persistent, long-term benefits were "attenuated" compared with the shorter-term benefits seen during the active phase, but nonetheless they persisted and were consistent across all subgroups studied, Dr. Chalmers said.
The ADVANCE and ADVANCE-ON studies were partly funded by Servier. Dr. Chalmers has received research grants and honoraria from that company. Dr. Rydén has been an adviser to AstraZeneca, Roche, Bristol-Myers Squibb, and Sanofi, and received research grants from Roche.
On Twitter @mitchelzoler
The findings from ADVANCE-ON are important. Clinicians need clear evidence that controlling a patient’s blood pressure produces long-term benefits, and the results from ADVANCE-ON provide this. We need many more studies that track the long-term impact of blood pressure reduction. Currently, a large fraction of patients with diabetes are not maintained at the recommended blood pressure levels. This report presents the longest follow-up of any antihypertensive intervention in patients with diabetes.
The findings also show that a small blood pressure reduction can have an important and long-lasting effect. This highlights the value of blood pressure control, even when the reduction achieved in an individual patient seems small.
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I believe that the effects linked with blood pressure reduction in ADVANCE-ON are likely generalizable to any antihypertensive regimen that produces a similar magnitude of effect. It is the blood pressure effect rather than the specific antihypertensive drugs used that is that critical, although drugs that affect the renin-angiotensin-aldosterone system are clearly the first choice for patients with diabetes and hypertension.
Dr. Lars Rydén is a cardiologist at the Karolinska Institute in Stockholm. He has been an adviser to AstraZeneca, Roche, Bristol-Myers Squibb, and Sanofi, and received research grants from Roche. He made these comments as designated discussant for the ADVANCE-ON report and in an interview.
The findings from ADVANCE-ON are important. Clinicians need clear evidence that controlling a patient’s blood pressure produces long-term benefits, and the results from ADVANCE-ON provide this. We need many more studies that track the long-term impact of blood pressure reduction. Currently, a large fraction of patients with diabetes are not maintained at the recommended blood pressure levels. This report presents the longest follow-up of any antihypertensive intervention in patients with diabetes.
The findings also show that a small blood pressure reduction can have an important and long-lasting effect. This highlights the value of blood pressure control, even when the reduction achieved in an individual patient seems small.
|
|
I believe that the effects linked with blood pressure reduction in ADVANCE-ON are likely generalizable to any antihypertensive regimen that produces a similar magnitude of effect. It is the blood pressure effect rather than the specific antihypertensive drugs used that is that critical, although drugs that affect the renin-angiotensin-aldosterone system are clearly the first choice for patients with diabetes and hypertension.
Dr. Lars Rydén is a cardiologist at the Karolinska Institute in Stockholm. He has been an adviser to AstraZeneca, Roche, Bristol-Myers Squibb, and Sanofi, and received research grants from Roche. He made these comments as designated discussant for the ADVANCE-ON report and in an interview.
The findings from ADVANCE-ON are important. Clinicians need clear evidence that controlling a patient’s blood pressure produces long-term benefits, and the results from ADVANCE-ON provide this. We need many more studies that track the long-term impact of blood pressure reduction. Currently, a large fraction of patients with diabetes are not maintained at the recommended blood pressure levels. This report presents the longest follow-up of any antihypertensive intervention in patients with diabetes.
The findings also show that a small blood pressure reduction can have an important and long-lasting effect. This highlights the value of blood pressure control, even when the reduction achieved in an individual patient seems small.
|
|
I believe that the effects linked with blood pressure reduction in ADVANCE-ON are likely generalizable to any antihypertensive regimen that produces a similar magnitude of effect. It is the blood pressure effect rather than the specific antihypertensive drugs used that is that critical, although drugs that affect the renin-angiotensin-aldosterone system are clearly the first choice for patients with diabetes and hypertension.
Dr. Lars Rydén is a cardiologist at the Karolinska Institute in Stockholm. He has been an adviser to AstraZeneca, Roche, Bristol-Myers Squibb, and Sanofi, and received research grants from Roche. He made these comments as designated discussant for the ADVANCE-ON report and in an interview.
BARCELONA – A modest amount of blood pressure control over an average of 4 years produced a significant, long-term survival benefit in patients with type 2 diabetes, based on a 10-year follow-up of more than 8,000 patients.
"It is critically important to maintain active blood-pressure lowering in both the short and long term in order to derive the greatest possible reductions in mortality and major cardiovascular events" in patients with type 2 diabetes, Dr. John Chalmers said at the annual congress of the European Society of Cardiology.
The results he reported showed that during 10 years of total follow-up, 4 years of concerted therapy with a dual antihypertensive-drug formulation on top of background therapy produced an average drop in blood pressure of 5.6/2.2 mm Hg, which was linked to a relative 9% decrease in mortality through the entire 10-year period.
Dr. Chalmers’ analysis used data from an average 6-year follow-up of patients after they completed a 4-year trial that had randomized them to treatment with either the combined formulation of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide, or to placebo. The 6-year assessment of these patients after they finished the closely regulated treatment phase while in the clinical trial is "the longest follow-up on the impact of blood pressure reduction in patients with diabetes," commented Dr. Lars Rydén, a cardiologist at the Karolinska Institute in Stockholm.
"The greatest part of the overall, cumulative benefit [over a 10-year period] was contributed by the carry forward of the in-trial benefits of active BP lowering," said Dr. Chalmers, senior director of the George Institute for Global Health in Sydney, Australia.
His study focused on data collected from patients enrolled in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation) trial. This study randomized 11,140 patients with type 2 diabetes who were at least 55 years old and had at least one additional cardiovascular disease risk factor, to treatment with the combined formulation on top of their preexisting medications or to placebo plus existing medications (Lancet 2007;370:829-40). Patients in the placebo group were unable to receive an angiotensin-converting enzyme inhibitor during the study. The study was sponsored by Servier, the company that markets a combined perindopril and indapamide formulation (Preterax).
At enrollment, ADVANCE patients averaged 66 years old, had an average 8-year history of type 2 diabetes, and had an average blood pressure of 145/81 mm Hg. Three-quarters were on an antihypertensive regimen of some kind at entry into the study.
During the study’s 4 years of active treatment, patients randomized to receive the perindopril and indapamide combination had significantly reduced blood pressure, compared with the control patients. After 4 years, this linked to a 9% relative drop in the combined incidence of major macrovascular and microvascular events (including cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction). Compared with the control group, this cut in events was statistically significant for the study’s primary endpoint. The antihypertensive intervention also was linked to a statistically significant, 14% relative drop in all-cause deaths.
To assess the longer-term impact of this 4-year intervention, Dr. Chalmers and his associates ran a post-trial observational study, ADVANCE-ON. Initially, 8,494 of the patients who completed ADVANCE (83% of surviving patients) agreed to participate in ADVANCE-ON; after another 6 years of follow-up, 5,131 patients remained under observation. During the extended 6 years of follow-up, patients from both the initial intervention arm and the initial control arm all maintained average blood pressures of roughly 137/75 mm Hg. The blood pressures of the original intervention and control patient arms "fully converged," Dr. Chalmers said.
During this 6-year period, patients received care from their personal physicians and could receive any antihypertensive regimen their physician prescribed. At their first follow-up medical examination after the end of the main ADVANCE study, about 40% of patients were on no antihypertensive drugs, 23% were on one drug, 21% were on two drugs, and the remainder were on higher numbers of antihypertensive drugs.
During the 6-year post-trial period, patients who had previously been in the active-treatment arm had a 6% relative reduction in all-cause mortality, compared with patients originally in the control arm, a difference that was not significant.
But when the researchers combined the 6-year post-trial follow-up with the in-trial results for a total median 10-year follow-up, they found an overall 9% relative cut in mortality in the intervention patients, compared with the controls, and a relative 12% drop in cardiovascular mortality.
The persistent, long-term benefits were "attenuated" compared with the shorter-term benefits seen during the active phase, but nonetheless they persisted and were consistent across all subgroups studied, Dr. Chalmers said.
The ADVANCE and ADVANCE-ON studies were partly funded by Servier. Dr. Chalmers has received research grants and honoraria from that company. Dr. Rydén has been an adviser to AstraZeneca, Roche, Bristol-Myers Squibb, and Sanofi, and received research grants from Roche.
On Twitter @mitchelzoler
BARCELONA – A modest amount of blood pressure control over an average of 4 years produced a significant, long-term survival benefit in patients with type 2 diabetes, based on a 10-year follow-up of more than 8,000 patients.
"It is critically important to maintain active blood-pressure lowering in both the short and long term in order to derive the greatest possible reductions in mortality and major cardiovascular events" in patients with type 2 diabetes, Dr. John Chalmers said at the annual congress of the European Society of Cardiology.
The results he reported showed that during 10 years of total follow-up, 4 years of concerted therapy with a dual antihypertensive-drug formulation on top of background therapy produced an average drop in blood pressure of 5.6/2.2 mm Hg, which was linked to a relative 9% decrease in mortality through the entire 10-year period.
Dr. Chalmers’ analysis used data from an average 6-year follow-up of patients after they completed a 4-year trial that had randomized them to treatment with either the combined formulation of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide, or to placebo. The 6-year assessment of these patients after they finished the closely regulated treatment phase while in the clinical trial is "the longest follow-up on the impact of blood pressure reduction in patients with diabetes," commented Dr. Lars Rydén, a cardiologist at the Karolinska Institute in Stockholm.
"The greatest part of the overall, cumulative benefit [over a 10-year period] was contributed by the carry forward of the in-trial benefits of active BP lowering," said Dr. Chalmers, senior director of the George Institute for Global Health in Sydney, Australia.
His study focused on data collected from patients enrolled in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation) trial. This study randomized 11,140 patients with type 2 diabetes who were at least 55 years old and had at least one additional cardiovascular disease risk factor, to treatment with the combined formulation on top of their preexisting medications or to placebo plus existing medications (Lancet 2007;370:829-40). Patients in the placebo group were unable to receive an angiotensin-converting enzyme inhibitor during the study. The study was sponsored by Servier, the company that markets a combined perindopril and indapamide formulation (Preterax).
At enrollment, ADVANCE patients averaged 66 years old, had an average 8-year history of type 2 diabetes, and had an average blood pressure of 145/81 mm Hg. Three-quarters were on an antihypertensive regimen of some kind at entry into the study.
During the study’s 4 years of active treatment, patients randomized to receive the perindopril and indapamide combination had significantly reduced blood pressure, compared with the control patients. After 4 years, this linked to a 9% relative drop in the combined incidence of major macrovascular and microvascular events (including cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction). Compared with the control group, this cut in events was statistically significant for the study’s primary endpoint. The antihypertensive intervention also was linked to a statistically significant, 14% relative drop in all-cause deaths.
To assess the longer-term impact of this 4-year intervention, Dr. Chalmers and his associates ran a post-trial observational study, ADVANCE-ON. Initially, 8,494 of the patients who completed ADVANCE (83% of surviving patients) agreed to participate in ADVANCE-ON; after another 6 years of follow-up, 5,131 patients remained under observation. During the extended 6 years of follow-up, patients from both the initial intervention arm and the initial control arm all maintained average blood pressures of roughly 137/75 mm Hg. The blood pressures of the original intervention and control patient arms "fully converged," Dr. Chalmers said.
During this 6-year period, patients received care from their personal physicians and could receive any antihypertensive regimen their physician prescribed. At their first follow-up medical examination after the end of the main ADVANCE study, about 40% of patients were on no antihypertensive drugs, 23% were on one drug, 21% were on two drugs, and the remainder were on higher numbers of antihypertensive drugs.
During the 6-year post-trial period, patients who had previously been in the active-treatment arm had a 6% relative reduction in all-cause mortality, compared with patients originally in the control arm, a difference that was not significant.
But when the researchers combined the 6-year post-trial follow-up with the in-trial results for a total median 10-year follow-up, they found an overall 9% relative cut in mortality in the intervention patients, compared with the controls, and a relative 12% drop in cardiovascular mortality.
The persistent, long-term benefits were "attenuated" compared with the shorter-term benefits seen during the active phase, but nonetheless they persisted and were consistent across all subgroups studied, Dr. Chalmers said.
The ADVANCE and ADVANCE-ON studies were partly funded by Servier. Dr. Chalmers has received research grants and honoraria from that company. Dr. Rydén has been an adviser to AstraZeneca, Roche, Bristol-Myers Squibb, and Sanofi, and received research grants from Roche.
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2014
Key clinical point: The survival benefit from 4 years of concerted antihypertensive treatment in patients with type 2 diabetes persisted for at least another 6 years.
Major finding: During a median 10-year follow-up, 4 years of active antihypertensive treatment cut mortality by 9%, compared with controls in diabetic patients.
Data source: ADVANCE-ON, a 10-year follow-up of 8,494 patients initially enrolled in ADVANCE, a 4-year, controlled, randomized trial that began with 11,140 patients with type 2 diabetes and at least one other cardiovascular risk factor.
Disclosures:. The ADVANCE and ADVANCE-ON studies were partly funded by Servier. Dr. Chalmers has received research grants and honoraria from that company. Dr. Rydén has been an adviser to AstraZeneca, Roche, Bristol-Myers Squibb, and Sanofi, and received research grants from Roche.
ACC/AHA risk calculator compares well with European SCORE
BARCELONA— Risk calculators are usually confined to certain populations, but the recently updated ACC/AHA calculator might be effective beyond the United States borders in a Southern European population.
Researchers from Portugal compared the ACC/AHA risk calculator to the European Systematic COronary Risk Evaluation (SCORE) in a patient population that was treated with lipid-lowering drugs. They found that the ACC/AHA calculator’s cut-off point at 7.5% was "extremely effective in discriminating high-risk subject," said Dr. Manuel Oliveira-Santos of Coimbra (Portugal) University, who presented the findings at the annual congress of the European Society of Cardiology.
They also found that that the two scoring systems were strongly correlated and well calibrated. Both calculators overestimated the cardiovascular (CV) risk, "which confirms the previous findings and shows that the calculator works, since many patients in the study were treated with statins," said Dr. Kim A. Williams Sr., president-elect of the American College of Cardiology, who was not involved in the study.
One of the main differences between the two calculators is that the ACC/AHA risk calculator predicts atherosclerotic cardiovascular disease (ASCVD) events, while SCORE estimates the individual risk of fatal noncoronary atherosclerotic and coronary heart disease only, said Dr. Oliveira-Santos.
The study's primary endpoint was acute myocardial infarction, stroke and CV death at 10 years, and the aim was to find out if the ASCVD could be a meaningful tool for this particular patient population in Portugal, said Dr. Oliveira-Santos.
The team retrospectively calculated the two scores for 446 CV-naive patients who were treated at a lipidology clinic between 1994 and 2007. Patients were divided to four groups according to the ASCVD (cut points at 5%, 7.5%, and 10%) and the SCORE system (cut points at 1%, 5%, and 10%).
The mean age of the population was 49 years; more than half were men; 21% were smokers, 25% had type 2 diabetes. More than half were on antihypertensive drug therapy and 72% were receiving statin treatment.
Researchers were able to follow up 85% of the patients at 10 years. Of those, 3.4% had an acute MI, 2.4% had a stroke, and 1.5% died of a cardiovascular event.
The median calculated CV death risk based on SCORE was 0.95%, and the median CV risk calculated by ASCVD was 8.5%. The observed event rate based on the SCORE definition was 1%, compared to 6% based on the ASCVD definition.
When ASCVD was applied to the study cohort, the majority of the patients fell at the very low (less than 5%) or very high (10% or higher) risk categories. About 20% of the patients were at medium risk categories.
Patients who fell in the low and very low risk categories – in other words, they had a CV risk of less than 7.5% – had – no actual cardiovascular events. In the 10% or higher risk group, the predicted event rate was nearly twice the observed rate.
The overestimation, especially in the low risk category (5% to 7.5%) could lead to unnecessary statin therapy and may raise some safety concerns, but the overestimation in the high-risk category is not problematic, Dr. Oliveira-Santos said.
Meanwhile, the group at medium-high risk (from 7.5% to less than 10%) had a slightly higher rate of actual CV events than that estimated using the calculator. "We don’t see that as a cause for concern since those are high risk patients in whom statin therapy is indicated. The statin-treated patients in our study are the majority," he said.
When the SCORE calculator was applied to the cohort, the CV death risk was overestimated in all groups. The majority of the patients fell in the very-low- or low-risk categories, and there were no CV deaths in the very-low-risk category, which included 51% of the patient population.
Researchers conducted further analysis and found that the SCORE and ASCVD systems were positively correlated and they both had "good and similar discriminative power," in addition to good calibration, Dr. Oliveira-Santos reported.
Dr. Williams said that the correlation of the two systems is good news. "There’s always going to be interest in how well an American score will predict the risk in a European population. And the fact that there’s good correlation is reassuring.
"And the most important thing is whether or not an individual practitioner in another country should feel comfortable using this calculator, and that’s why we need more of this kind of study — to find out if they need to build another application or whether they can use what we’ve already created," said Dr. Williams, professor and chief of cardiology at Rush University in Chicago.
Dr. Oliveira-Santos and Dr. Williams had no relevant financial disclosures.
Twitter: @naseemmiller
BARCELONA— Risk calculators are usually confined to certain populations, but the recently updated ACC/AHA calculator might be effective beyond the United States borders in a Southern European population.
Researchers from Portugal compared the ACC/AHA risk calculator to the European Systematic COronary Risk Evaluation (SCORE) in a patient population that was treated with lipid-lowering drugs. They found that the ACC/AHA calculator’s cut-off point at 7.5% was "extremely effective in discriminating high-risk subject," said Dr. Manuel Oliveira-Santos of Coimbra (Portugal) University, who presented the findings at the annual congress of the European Society of Cardiology.
They also found that that the two scoring systems were strongly correlated and well calibrated. Both calculators overestimated the cardiovascular (CV) risk, "which confirms the previous findings and shows that the calculator works, since many patients in the study were treated with statins," said Dr. Kim A. Williams Sr., president-elect of the American College of Cardiology, who was not involved in the study.
One of the main differences between the two calculators is that the ACC/AHA risk calculator predicts atherosclerotic cardiovascular disease (ASCVD) events, while SCORE estimates the individual risk of fatal noncoronary atherosclerotic and coronary heart disease only, said Dr. Oliveira-Santos.
The study's primary endpoint was acute myocardial infarction, stroke and CV death at 10 years, and the aim was to find out if the ASCVD could be a meaningful tool for this particular patient population in Portugal, said Dr. Oliveira-Santos.
The team retrospectively calculated the two scores for 446 CV-naive patients who were treated at a lipidology clinic between 1994 and 2007. Patients were divided to four groups according to the ASCVD (cut points at 5%, 7.5%, and 10%) and the SCORE system (cut points at 1%, 5%, and 10%).
The mean age of the population was 49 years; more than half were men; 21% were smokers, 25% had type 2 diabetes. More than half were on antihypertensive drug therapy and 72% were receiving statin treatment.
Researchers were able to follow up 85% of the patients at 10 years. Of those, 3.4% had an acute MI, 2.4% had a stroke, and 1.5% died of a cardiovascular event.
The median calculated CV death risk based on SCORE was 0.95%, and the median CV risk calculated by ASCVD was 8.5%. The observed event rate based on the SCORE definition was 1%, compared to 6% based on the ASCVD definition.
When ASCVD was applied to the study cohort, the majority of the patients fell at the very low (less than 5%) or very high (10% or higher) risk categories. About 20% of the patients were at medium risk categories.
Patients who fell in the low and very low risk categories – in other words, they had a CV risk of less than 7.5% – had – no actual cardiovascular events. In the 10% or higher risk group, the predicted event rate was nearly twice the observed rate.
The overestimation, especially in the low risk category (5% to 7.5%) could lead to unnecessary statin therapy and may raise some safety concerns, but the overestimation in the high-risk category is not problematic, Dr. Oliveira-Santos said.
Meanwhile, the group at medium-high risk (from 7.5% to less than 10%) had a slightly higher rate of actual CV events than that estimated using the calculator. "We don’t see that as a cause for concern since those are high risk patients in whom statin therapy is indicated. The statin-treated patients in our study are the majority," he said.
When the SCORE calculator was applied to the cohort, the CV death risk was overestimated in all groups. The majority of the patients fell in the very-low- or low-risk categories, and there were no CV deaths in the very-low-risk category, which included 51% of the patient population.
Researchers conducted further analysis and found that the SCORE and ASCVD systems were positively correlated and they both had "good and similar discriminative power," in addition to good calibration, Dr. Oliveira-Santos reported.
Dr. Williams said that the correlation of the two systems is good news. "There’s always going to be interest in how well an American score will predict the risk in a European population. And the fact that there’s good correlation is reassuring.
"And the most important thing is whether or not an individual practitioner in another country should feel comfortable using this calculator, and that’s why we need more of this kind of study — to find out if they need to build another application or whether they can use what we’ve already created," said Dr. Williams, professor and chief of cardiology at Rush University in Chicago.
Dr. Oliveira-Santos and Dr. Williams had no relevant financial disclosures.
Twitter: @naseemmiller
BARCELONA— Risk calculators are usually confined to certain populations, but the recently updated ACC/AHA calculator might be effective beyond the United States borders in a Southern European population.
Researchers from Portugal compared the ACC/AHA risk calculator to the European Systematic COronary Risk Evaluation (SCORE) in a patient population that was treated with lipid-lowering drugs. They found that the ACC/AHA calculator’s cut-off point at 7.5% was "extremely effective in discriminating high-risk subject," said Dr. Manuel Oliveira-Santos of Coimbra (Portugal) University, who presented the findings at the annual congress of the European Society of Cardiology.
They also found that that the two scoring systems were strongly correlated and well calibrated. Both calculators overestimated the cardiovascular (CV) risk, "which confirms the previous findings and shows that the calculator works, since many patients in the study were treated with statins," said Dr. Kim A. Williams Sr., president-elect of the American College of Cardiology, who was not involved in the study.
One of the main differences between the two calculators is that the ACC/AHA risk calculator predicts atherosclerotic cardiovascular disease (ASCVD) events, while SCORE estimates the individual risk of fatal noncoronary atherosclerotic and coronary heart disease only, said Dr. Oliveira-Santos.
The study's primary endpoint was acute myocardial infarction, stroke and CV death at 10 years, and the aim was to find out if the ASCVD could be a meaningful tool for this particular patient population in Portugal, said Dr. Oliveira-Santos.
The team retrospectively calculated the two scores for 446 CV-naive patients who were treated at a lipidology clinic between 1994 and 2007. Patients were divided to four groups according to the ASCVD (cut points at 5%, 7.5%, and 10%) and the SCORE system (cut points at 1%, 5%, and 10%).
The mean age of the population was 49 years; more than half were men; 21% were smokers, 25% had type 2 diabetes. More than half were on antihypertensive drug therapy and 72% were receiving statin treatment.
Researchers were able to follow up 85% of the patients at 10 years. Of those, 3.4% had an acute MI, 2.4% had a stroke, and 1.5% died of a cardiovascular event.
The median calculated CV death risk based on SCORE was 0.95%, and the median CV risk calculated by ASCVD was 8.5%. The observed event rate based on the SCORE definition was 1%, compared to 6% based on the ASCVD definition.
When ASCVD was applied to the study cohort, the majority of the patients fell at the very low (less than 5%) or very high (10% or higher) risk categories. About 20% of the patients were at medium risk categories.
Patients who fell in the low and very low risk categories – in other words, they had a CV risk of less than 7.5% – had – no actual cardiovascular events. In the 10% or higher risk group, the predicted event rate was nearly twice the observed rate.
The overestimation, especially in the low risk category (5% to 7.5%) could lead to unnecessary statin therapy and may raise some safety concerns, but the overestimation in the high-risk category is not problematic, Dr. Oliveira-Santos said.
Meanwhile, the group at medium-high risk (from 7.5% to less than 10%) had a slightly higher rate of actual CV events than that estimated using the calculator. "We don’t see that as a cause for concern since those are high risk patients in whom statin therapy is indicated. The statin-treated patients in our study are the majority," he said.
When the SCORE calculator was applied to the cohort, the CV death risk was overestimated in all groups. The majority of the patients fell in the very-low- or low-risk categories, and there were no CV deaths in the very-low-risk category, which included 51% of the patient population.
Researchers conducted further analysis and found that the SCORE and ASCVD systems were positively correlated and they both had "good and similar discriminative power," in addition to good calibration, Dr. Oliveira-Santos reported.
Dr. Williams said that the correlation of the two systems is good news. "There’s always going to be interest in how well an American score will predict the risk in a European population. And the fact that there’s good correlation is reassuring.
"And the most important thing is whether or not an individual practitioner in another country should feel comfortable using this calculator, and that’s why we need more of this kind of study — to find out if they need to build another application or whether they can use what we’ve already created," said Dr. Williams, professor and chief of cardiology at Rush University in Chicago.
Dr. Oliveira-Santos and Dr. Williams had no relevant financial disclosures.
Twitter: @naseemmiller
AT THE ESC CONGRESS 2014
Key clinical finding: The ACC/AHA risk calculator effectively identified high-risk patients in Portugal who were on statin therapy.
Major Finding: The median calculated CV death risk based on SCORE was 0.95%, and the median CV risk calculated by ASCVD was 8.5%.
Data Source: Analysis of 10-year follow-up data from 446 patients treated at a lipidology clinic in Portugal.
Disclosures: Dr. Oliveira-Santos and Dr. Williams had no relevant financial disclosures.
Diabetes increases risk of atrial fibrillation
BARCELONA – Adults with diabetes mellitus are at increased risk of subsequent new-onset atrial fibrillation – and the younger the age at diabetes onset, the greater the likelihood of developing the arrhythmia.
That’s the key finding from a Danish national registry study in which all 5,168,416 Danish adults without atrial fibrillation in 1996 were followed through 2012 for development of atrial fibrillation (AF). The study population included 75,197 Danes with diabetes at baseline and another 235,327 who developed the disease during follow-up, Dr. Jannik L. Pallisgaard explained at the annual congress of the European Society of Cardiology.
During follow-up, 5.6% of those with diabetes and 3.3% of those without diabetes developed AF. The mean time from diabetes onset to AF onset was 5 years, reported Dr. Pallisgaard of the University of Copenhagen.
"What was particularly interesting, I think, is that we found the youngest patients were the group at highest risk" of developing AF, he said. "We suggest that starting at the onset of diabetes, routine pulse palpation, ECGs, and focused patient interviews asking about any signs of atrial fibrillation could prove beneficial in detecting the arrhythmia."
The incidence rate ratio for developing AF per 1,000 person-years of follow-up was roughly 2.5-fold greater in 18- to 39-year-olds with diabetes than in their nondiabetic peers. From this peak rate in young adults, the magnitude of relative risk dropped in stepwise fashion with age: The variability in risk was lower in 40- to 60-year-old diabetics than in the 18- to 39-year olds and lower still in 65- to 74-year olds. Variability in the incidence rate ratio finally bottomed out at a still statistically significant 1.3-fold increased risk of developing AF in diabetic individuals ages 75 and older compared to their nondiabetic peers.
Dr. Pallisgaard noted that while the relative risk of developing AF was greatest in the 18- to 39-year-olds, the absolute number of new cases of AF was far greater in older patients because there were so many more of them with diabetes. He cautioned that as the obesity epidemic leads to more and more patients developing type 2 diabetes at younger ages, more cases of AF can be expected in young adults.
Dr. Pallisgaard cited two likely mechanisms underlying the observed increased risk of AF in diabetic patients: left ventricular hypertrophy and vascular inflammation, which are both often present in the diabetic population.
He reported having no financial conflicts regarding this study, conducted with Danish institutional research funds.
BARCELONA – Adults with diabetes mellitus are at increased risk of subsequent new-onset atrial fibrillation – and the younger the age at diabetes onset, the greater the likelihood of developing the arrhythmia.
That’s the key finding from a Danish national registry study in which all 5,168,416 Danish adults without atrial fibrillation in 1996 were followed through 2012 for development of atrial fibrillation (AF). The study population included 75,197 Danes with diabetes at baseline and another 235,327 who developed the disease during follow-up, Dr. Jannik L. Pallisgaard explained at the annual congress of the European Society of Cardiology.
During follow-up, 5.6% of those with diabetes and 3.3% of those without diabetes developed AF. The mean time from diabetes onset to AF onset was 5 years, reported Dr. Pallisgaard of the University of Copenhagen.
"What was particularly interesting, I think, is that we found the youngest patients were the group at highest risk" of developing AF, he said. "We suggest that starting at the onset of diabetes, routine pulse palpation, ECGs, and focused patient interviews asking about any signs of atrial fibrillation could prove beneficial in detecting the arrhythmia."
The incidence rate ratio for developing AF per 1,000 person-years of follow-up was roughly 2.5-fold greater in 18- to 39-year-olds with diabetes than in their nondiabetic peers. From this peak rate in young adults, the magnitude of relative risk dropped in stepwise fashion with age: The variability in risk was lower in 40- to 60-year-old diabetics than in the 18- to 39-year olds and lower still in 65- to 74-year olds. Variability in the incidence rate ratio finally bottomed out at a still statistically significant 1.3-fold increased risk of developing AF in diabetic individuals ages 75 and older compared to their nondiabetic peers.
Dr. Pallisgaard noted that while the relative risk of developing AF was greatest in the 18- to 39-year-olds, the absolute number of new cases of AF was far greater in older patients because there were so many more of them with diabetes. He cautioned that as the obesity epidemic leads to more and more patients developing type 2 diabetes at younger ages, more cases of AF can be expected in young adults.
Dr. Pallisgaard cited two likely mechanisms underlying the observed increased risk of AF in diabetic patients: left ventricular hypertrophy and vascular inflammation, which are both often present in the diabetic population.
He reported having no financial conflicts regarding this study, conducted with Danish institutional research funds.
BARCELONA – Adults with diabetes mellitus are at increased risk of subsequent new-onset atrial fibrillation – and the younger the age at diabetes onset, the greater the likelihood of developing the arrhythmia.
That’s the key finding from a Danish national registry study in which all 5,168,416 Danish adults without atrial fibrillation in 1996 were followed through 2012 for development of atrial fibrillation (AF). The study population included 75,197 Danes with diabetes at baseline and another 235,327 who developed the disease during follow-up, Dr. Jannik L. Pallisgaard explained at the annual congress of the European Society of Cardiology.
During follow-up, 5.6% of those with diabetes and 3.3% of those without diabetes developed AF. The mean time from diabetes onset to AF onset was 5 years, reported Dr. Pallisgaard of the University of Copenhagen.
"What was particularly interesting, I think, is that we found the youngest patients were the group at highest risk" of developing AF, he said. "We suggest that starting at the onset of diabetes, routine pulse palpation, ECGs, and focused patient interviews asking about any signs of atrial fibrillation could prove beneficial in detecting the arrhythmia."
The incidence rate ratio for developing AF per 1,000 person-years of follow-up was roughly 2.5-fold greater in 18- to 39-year-olds with diabetes than in their nondiabetic peers. From this peak rate in young adults, the magnitude of relative risk dropped in stepwise fashion with age: The variability in risk was lower in 40- to 60-year-old diabetics than in the 18- to 39-year olds and lower still in 65- to 74-year olds. Variability in the incidence rate ratio finally bottomed out at a still statistically significant 1.3-fold increased risk of developing AF in diabetic individuals ages 75 and older compared to their nondiabetic peers.
Dr. Pallisgaard noted that while the relative risk of developing AF was greatest in the 18- to 39-year-olds, the absolute number of new cases of AF was far greater in older patients because there were so many more of them with diabetes. He cautioned that as the obesity epidemic leads to more and more patients developing type 2 diabetes at younger ages, more cases of AF can be expected in young adults.
Dr. Pallisgaard cited two likely mechanisms underlying the observed increased risk of AF in diabetic patients: left ventricular hypertrophy and vascular inflammation, which are both often present in the diabetic population.
He reported having no financial conflicts regarding this study, conducted with Danish institutional research funds.
AT THE ESC CONGRESS 2014
Key clinical point: Starting at the onset of diabetes, routine pulse palpation, ECGs, and patient interviews focused on signs of atrial fibrillation might improve detection of the arrhythmia.
Major finding: During follow-up, 5.6% of those with diabetes and 3.3% of those without diabetes developed AF.
Data source: This was a national registry study including all of the nearly 5.2 million Danish adults without atrial fibrillation in 1996. Follow-up ran through 2012.
Disclosures: The presenter reported having no financial conflicts regarding this study, funded by Danish institutional research grants.
Liraglutide tested as add-on therapy for type 1 diabetes
LAS VEGAS – In patients with type 1 diabetes, adding a 1.8-mg daily dose of liraglutide to insulin significantly reduced hemoglobin A1c, mean blood glucose, body weight, carbohydrate intake, and C-reactive protein, in a randomized study.
The 72-patient study also showed that adding liraglutide (Victoza) significantly improved quality of life and reduced systolic blood pressure in the groups that were receiving higher doses of the medicine.
"Our findings have significant implications for the future treatment of type 1 diabetes," said Dr. Nitesh Kuhadiya of the State University of New York at Buffalo, who presented the findings at the annual meeting of the American Association of Clinical Endocrinologists. "Long term studies are needed to establish the durability of the effects."
In previous small, nonrandomized studies of patients with type 1 diabetes, liraglutide improved glycemic control and led to weight loss (Eur. J. Endocrinol. 2011;165:77-84; Endocr. Pract. 2013;19:963-7). They then decided to conduct a randomized controlled trial, which is the first of its kind, said Dr. Kuhadiya, who compared type 1 diabetes to a "wild horse that’s extremely difficult to tame and kicks you 10 times a day."
For the study, researchers randomized 72 patients to four groups to receive 0.6, 1.2, or 1.8 mg of liraglutide or a placebo daily for 12 weeks. One patient dropped out of placebo group, as well as five from the 1.2-mg and three from the 1.8-mg group.
The groups’ baseline characteristics were similar. All patients had type 1 diabetes for at least 1 year, were on insulin therapy, and had no detectable C-peptide in plasma. The mean age was 44 years, mean body weight was 83 kg, mean body mass index was 29 kg/m2, mean HbA1c was 7.5, and mean interval since diabetes diagnosis was 20 years. Nearly all (96%) patients were white and 56% were women.
There was a significant drop of nearly 10 mg/dL in average glucose in the 1.2- and 1.8-mg groups. The HbA1c, also dropped in those two groups, although it was significant in only the 1.2-mg group, by about 0.8%. The drop was 0.4% in 1.8-mg group, 0.2% in the 0.6-mg group, and 0.3% in the placebo subjects.
There were also significant changes in the percent time spent in different glycemic thresholds for the 1.8-mg group.
Patients on 1.2 mg and 1.8 mg of liraglutide spent about 3%-5% more time in the 70- to 160-mg/dL zone, respectively, although only those on 1.8 mg reached statistical significance.
Again, the 1.2- and 1.8-mg groups spent less time in hyperglycemia, defined as 160-240 mg/dL, Dr. Kuhadiya said. No significant changes were observed in the other two groups.
A similar trend was seen for severe hyperglycemia (250 mg/dL).
There was, however, some additional hypoglycemia in the study in the range of 55 to 70 mg/dL, Dr. Kuhadiya reported. The 1.2- and 1.8-mg groups spent significantly more time (nearly 1%) in that range, but there was no incidence of hypoglycemia in the placebo and 0.6-mg groups. The results were similar for the less than 50 mg/dL range. However, there was no incidence of hypoglycemia requiring hospitalization or medical attention, Dr. Kuhadiya said.
All three groups receiving liraglutide showed significant weight loss: nearly 5 kg in the 1.2- and 1.8-mg groups, and 3 kg in the 0.6-mg group, over a period of 12 weeks.
The carbohydrate intake for the 1.2- and 1.8-mg groups also dropped significantly.
Dr. Kuhadiya said that the findings also show that all changes are independent of each other.
All groups showed a fall in C-reactive protein, which is a marker for cardiovascular risk, although only the 1.8-mg groups showed a statistical significance. "And this is important because most patients with type 1 diabetes have metabolic syndrome, and to be able to demonstrate all these changes and an additional fall in CRP means further protection from cardiovascular risk," Dr. Kuhadiya said.
The study was funded by Novo Nordisk. Dr. Kuhadiya had no relevant disclosures.
On Twitter @naseemmiller
The drug works. It makes sense. This study proves it. I think there’s a lot of potential for use of GLP-1 [glucagonlike peptide–1] agonists as additional therapy to insulin in type 1 diabetes given their unique mode of action, and especially since today many patients are overweight. About 35% of type 1 diabetes patients, and maybe even more, are beginning to show insulin resistance because they’re overweight. Getting a drug on board that promotes weight loss as well as helps control blood sugar is very valuable.
The drug is already being prescribed to some extent on an off-label basis, but insurance companies don’t approve or reimburse for its use in type 1 diabetes.
Paul Jellinger, M.D., is professor of clinical medicine at the University of Miami and an endocrinologist in Hollywood, Fla. He is on the speakers bureaus for Novo Nordisk, Boehringer Ingelheim, Janssen, Bristol-Myers Squibb, and Amarin. He was not involved in the study.
The drug works. It makes sense. This study proves it. I think there’s a lot of potential for use of GLP-1 [glucagonlike peptide–1] agonists as additional therapy to insulin in type 1 diabetes given their unique mode of action, and especially since today many patients are overweight. About 35% of type 1 diabetes patients, and maybe even more, are beginning to show insulin resistance because they’re overweight. Getting a drug on board that promotes weight loss as well as helps control blood sugar is very valuable.
The drug is already being prescribed to some extent on an off-label basis, but insurance companies don’t approve or reimburse for its use in type 1 diabetes.
Paul Jellinger, M.D., is professor of clinical medicine at the University of Miami and an endocrinologist in Hollywood, Fla. He is on the speakers bureaus for Novo Nordisk, Boehringer Ingelheim, Janssen, Bristol-Myers Squibb, and Amarin. He was not involved in the study.
The drug works. It makes sense. This study proves it. I think there’s a lot of potential for use of GLP-1 [glucagonlike peptide–1] agonists as additional therapy to insulin in type 1 diabetes given their unique mode of action, and especially since today many patients are overweight. About 35% of type 1 diabetes patients, and maybe even more, are beginning to show insulin resistance because they’re overweight. Getting a drug on board that promotes weight loss as well as helps control blood sugar is very valuable.
The drug is already being prescribed to some extent on an off-label basis, but insurance companies don’t approve or reimburse for its use in type 1 diabetes.
Paul Jellinger, M.D., is professor of clinical medicine at the University of Miami and an endocrinologist in Hollywood, Fla. He is on the speakers bureaus for Novo Nordisk, Boehringer Ingelheim, Janssen, Bristol-Myers Squibb, and Amarin. He was not involved in the study.
LAS VEGAS – In patients with type 1 diabetes, adding a 1.8-mg daily dose of liraglutide to insulin significantly reduced hemoglobin A1c, mean blood glucose, body weight, carbohydrate intake, and C-reactive protein, in a randomized study.
The 72-patient study also showed that adding liraglutide (Victoza) significantly improved quality of life and reduced systolic blood pressure in the groups that were receiving higher doses of the medicine.
"Our findings have significant implications for the future treatment of type 1 diabetes," said Dr. Nitesh Kuhadiya of the State University of New York at Buffalo, who presented the findings at the annual meeting of the American Association of Clinical Endocrinologists. "Long term studies are needed to establish the durability of the effects."
In previous small, nonrandomized studies of patients with type 1 diabetes, liraglutide improved glycemic control and led to weight loss (Eur. J. Endocrinol. 2011;165:77-84; Endocr. Pract. 2013;19:963-7). They then decided to conduct a randomized controlled trial, which is the first of its kind, said Dr. Kuhadiya, who compared type 1 diabetes to a "wild horse that’s extremely difficult to tame and kicks you 10 times a day."
For the study, researchers randomized 72 patients to four groups to receive 0.6, 1.2, or 1.8 mg of liraglutide or a placebo daily for 12 weeks. One patient dropped out of placebo group, as well as five from the 1.2-mg and three from the 1.8-mg group.
The groups’ baseline characteristics were similar. All patients had type 1 diabetes for at least 1 year, were on insulin therapy, and had no detectable C-peptide in plasma. The mean age was 44 years, mean body weight was 83 kg, mean body mass index was 29 kg/m2, mean HbA1c was 7.5, and mean interval since diabetes diagnosis was 20 years. Nearly all (96%) patients were white and 56% were women.
There was a significant drop of nearly 10 mg/dL in average glucose in the 1.2- and 1.8-mg groups. The HbA1c, also dropped in those two groups, although it was significant in only the 1.2-mg group, by about 0.8%. The drop was 0.4% in 1.8-mg group, 0.2% in the 0.6-mg group, and 0.3% in the placebo subjects.
There were also significant changes in the percent time spent in different glycemic thresholds for the 1.8-mg group.
Patients on 1.2 mg and 1.8 mg of liraglutide spent about 3%-5% more time in the 70- to 160-mg/dL zone, respectively, although only those on 1.8 mg reached statistical significance.
Again, the 1.2- and 1.8-mg groups spent less time in hyperglycemia, defined as 160-240 mg/dL, Dr. Kuhadiya said. No significant changes were observed in the other two groups.
A similar trend was seen for severe hyperglycemia (250 mg/dL).
There was, however, some additional hypoglycemia in the study in the range of 55 to 70 mg/dL, Dr. Kuhadiya reported. The 1.2- and 1.8-mg groups spent significantly more time (nearly 1%) in that range, but there was no incidence of hypoglycemia in the placebo and 0.6-mg groups. The results were similar for the less than 50 mg/dL range. However, there was no incidence of hypoglycemia requiring hospitalization or medical attention, Dr. Kuhadiya said.
All three groups receiving liraglutide showed significant weight loss: nearly 5 kg in the 1.2- and 1.8-mg groups, and 3 kg in the 0.6-mg group, over a period of 12 weeks.
The carbohydrate intake for the 1.2- and 1.8-mg groups also dropped significantly.
Dr. Kuhadiya said that the findings also show that all changes are independent of each other.
All groups showed a fall in C-reactive protein, which is a marker for cardiovascular risk, although only the 1.8-mg groups showed a statistical significance. "And this is important because most patients with type 1 diabetes have metabolic syndrome, and to be able to demonstrate all these changes and an additional fall in CRP means further protection from cardiovascular risk," Dr. Kuhadiya said.
The study was funded by Novo Nordisk. Dr. Kuhadiya had no relevant disclosures.
On Twitter @naseemmiller
LAS VEGAS – In patients with type 1 diabetes, adding a 1.8-mg daily dose of liraglutide to insulin significantly reduced hemoglobin A1c, mean blood glucose, body weight, carbohydrate intake, and C-reactive protein, in a randomized study.
The 72-patient study also showed that adding liraglutide (Victoza) significantly improved quality of life and reduced systolic blood pressure in the groups that were receiving higher doses of the medicine.
"Our findings have significant implications for the future treatment of type 1 diabetes," said Dr. Nitesh Kuhadiya of the State University of New York at Buffalo, who presented the findings at the annual meeting of the American Association of Clinical Endocrinologists. "Long term studies are needed to establish the durability of the effects."
In previous small, nonrandomized studies of patients with type 1 diabetes, liraglutide improved glycemic control and led to weight loss (Eur. J. Endocrinol. 2011;165:77-84; Endocr. Pract. 2013;19:963-7). They then decided to conduct a randomized controlled trial, which is the first of its kind, said Dr. Kuhadiya, who compared type 1 diabetes to a "wild horse that’s extremely difficult to tame and kicks you 10 times a day."
For the study, researchers randomized 72 patients to four groups to receive 0.6, 1.2, or 1.8 mg of liraglutide or a placebo daily for 12 weeks. One patient dropped out of placebo group, as well as five from the 1.2-mg and three from the 1.8-mg group.
The groups’ baseline characteristics were similar. All patients had type 1 diabetes for at least 1 year, were on insulin therapy, and had no detectable C-peptide in plasma. The mean age was 44 years, mean body weight was 83 kg, mean body mass index was 29 kg/m2, mean HbA1c was 7.5, and mean interval since diabetes diagnosis was 20 years. Nearly all (96%) patients were white and 56% were women.
There was a significant drop of nearly 10 mg/dL in average glucose in the 1.2- and 1.8-mg groups. The HbA1c, also dropped in those two groups, although it was significant in only the 1.2-mg group, by about 0.8%. The drop was 0.4% in 1.8-mg group, 0.2% in the 0.6-mg group, and 0.3% in the placebo subjects.
There were also significant changes in the percent time spent in different glycemic thresholds for the 1.8-mg group.
Patients on 1.2 mg and 1.8 mg of liraglutide spent about 3%-5% more time in the 70- to 160-mg/dL zone, respectively, although only those on 1.8 mg reached statistical significance.
Again, the 1.2- and 1.8-mg groups spent less time in hyperglycemia, defined as 160-240 mg/dL, Dr. Kuhadiya said. No significant changes were observed in the other two groups.
A similar trend was seen for severe hyperglycemia (250 mg/dL).
There was, however, some additional hypoglycemia in the study in the range of 55 to 70 mg/dL, Dr. Kuhadiya reported. The 1.2- and 1.8-mg groups spent significantly more time (nearly 1%) in that range, but there was no incidence of hypoglycemia in the placebo and 0.6-mg groups. The results were similar for the less than 50 mg/dL range. However, there was no incidence of hypoglycemia requiring hospitalization or medical attention, Dr. Kuhadiya said.
All three groups receiving liraglutide showed significant weight loss: nearly 5 kg in the 1.2- and 1.8-mg groups, and 3 kg in the 0.6-mg group, over a period of 12 weeks.
The carbohydrate intake for the 1.2- and 1.8-mg groups also dropped significantly.
Dr. Kuhadiya said that the findings also show that all changes are independent of each other.
All groups showed a fall in C-reactive protein, which is a marker for cardiovascular risk, although only the 1.8-mg groups showed a statistical significance. "And this is important because most patients with type 1 diabetes have metabolic syndrome, and to be able to demonstrate all these changes and an additional fall in CRP means further protection from cardiovascular risk," Dr. Kuhadiya said.
The study was funded by Novo Nordisk. Dr. Kuhadiya had no relevant disclosures.
On Twitter @naseemmiller
AT AACE 2014
Key clinical point: Liraglutide may help type 1 diabetes patients control glucose and lose weight.
Major finding: There was a significant drop of nearly 10 mg/dL in average glucose in the 1.2-mg and 1.8-mg groups.
Data source: Randomized controlled trial of 72 patients receiving 0.6, 1.2, or 1.8 mg of liraglutide or a placebo daily for 12 weeks.
Disclosures: The study was funded by Novo Nordisk. Dr. Kuhadiya had no relevant disclosures.
Islet transplants aided type 1 diabetes patients
SAN FRANCISCO – Half of 48 adults with type 1 diabetes, impaired awareness of hypoglycemia, and a history of severe hypoglycemia were able to stop insulin therapy after experimental transplantation of human pancreatic islet cells in a prospective, phase III trial.
The National Institute of Health’s Clinical Islet Transplantation Consortium reported partial, initial results from 365 days of follow-up after islet-cell transplantation in the eight-center study. Speaking for the consortium at the annual scientific sessions of the American Diabetes Association, Dr. Bernhard J. Hering withheld results for the primary outcome measure (the proportion of patients who had a hemoglobin A1c of less than 7% at day 365 and no severe hypoglycemia in days 28 through 365 after the first islet transplant) pending its publication, he said.
Still, results for secondary measures of effectiveness and safety were good enough that "islet transplantation should be considered in this subgroup of patients when other treatment options have failed," said Dr. Hering, a professor of surgery and director of the Islet Cell Transplantation Program at the University of Minnesota, Minneapolis.
The study included patients who had had type 1 diabetes for at least 5 years, with stimulated C-peptide levels below 0.3 ng/mL (considered "absent") and at least one episode of severe hypoglycemia in the prior year with documentation of reduced hypoglycemia awareness and/or marked glycemic lability, if they didn’t meet any of 32 exclusion criteria. All patients underwent immunosuppression as part of the transplantation protocol.
Of the 48 patients, 26 received a second islet cell transplantation, and 1 received a third transplantation. Islet grafts were functioning in more than 90% of patients at day 365 of follow-up, he and his associates reported.
At day 365, roughly 50% of patients were insulin free. Insulin use decreased significantly to a median of 0 unit/kg per day at day 365.
Serum glucose levels and C-peptide secretion during mixed-meal tolerance tests improved over time after transplantation. Clarke scores and Ryan scores to assess patient awareness of hypoglycemia both improved significantly by day 365, as did measures of the glycemic lability index and the mean amplitude of glycemic excursions.
The median percentage of time spent within the desired glucose range increased from about 50% at baseline to nearly 95% at day 365, Dr. Hering reported.
The 19 serious adverse events included 5 that were procedure related (bleeding after percutaneous cannulation of a portal vein), 13 transient events related to immunosuppression (neutropenia, cytokine release, or elevated liver function test results), and 1 episode of hypoglycemia in a patient on insulin. None of these events caused death, disability, or permanent sequelae. Among other adverse events, a small but statistically significant drop in glomerular function test results was associated with the start of immunosuppression, six patients had calculated panel reactive antibodies above zero, and one patient developed acute kidney injury for unclear reasons.
The investigators plan further long-term follow-up.
Registry data suggest that approximately 35% of U.S. patients with type 1 diabetes each year report severe hypoglycemia requiring assistance, Dr. Hering said.
Dr. Hering has been a consultant for Novartis, Janssen, Novo Nordisk, Otsuka, and Sanofi.
On Twitter @sherryboschert
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This is another of the government-funded trials looking at clinical islet-cell transplantation, which are critically important because they have some success in some patients. This does offer promise for people who have hypoglycemia unawareness to the point where they are unable to function in their lives, but we need to find that out from the primary outcome results, which have not been presented. I would not use this treatment at this time.
The indication for islet-cell transplantation was severe hypoglycemia in someone with type 1 diabetes. This identifies a group that may have particular risks with standard therapy, in whom there may be justification for exposing them to the potential side effects of the transplant. That approach changes the risk-benefit ratio – that’s the way I interpret it.
The other exciting piece from this particular study is that it was a multisite project, and they had to do islet isolation at each site under standardized conditions, which is new. If we’re ever going to bring islet transplantation forward as a therapy and have it be approved by the Food and Drug Administration, there must be tremendous standardization in how islets are harvested and prepared for use. The fact that they were able to do that is very exciting.
Dr. Elizabeth R. Seaquist is a professor of medicine and the Pennock Family Chair in Diabetes Research at the University of Minnesota, Minneapolis. She gave these comments in an interview at the meeting. Dr. Seaquist is a colleague of Dr. Hering at the university. She reported financial associations with multiple companies but said none are relevant to this topic.
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This is another of the government-funded trials looking at clinical islet-cell transplantation, which are critically important because they have some success in some patients. This does offer promise for people who have hypoglycemia unawareness to the point where they are unable to function in their lives, but we need to find that out from the primary outcome results, which have not been presented. I would not use this treatment at this time.
The indication for islet-cell transplantation was severe hypoglycemia in someone with type 1 diabetes. This identifies a group that may have particular risks with standard therapy, in whom there may be justification for exposing them to the potential side effects of the transplant. That approach changes the risk-benefit ratio – that’s the way I interpret it.
The other exciting piece from this particular study is that it was a multisite project, and they had to do islet isolation at each site under standardized conditions, which is new. If we’re ever going to bring islet transplantation forward as a therapy and have it be approved by the Food and Drug Administration, there must be tremendous standardization in how islets are harvested and prepared for use. The fact that they were able to do that is very exciting.
Dr. Elizabeth R. Seaquist is a professor of medicine and the Pennock Family Chair in Diabetes Research at the University of Minnesota, Minneapolis. She gave these comments in an interview at the meeting. Dr. Seaquist is a colleague of Dr. Hering at the university. She reported financial associations with multiple companies but said none are relevant to this topic.
|
|
This is another of the government-funded trials looking at clinical islet-cell transplantation, which are critically important because they have some success in some patients. This does offer promise for people who have hypoglycemia unawareness to the point where they are unable to function in their lives, but we need to find that out from the primary outcome results, which have not been presented. I would not use this treatment at this time.
The indication for islet-cell transplantation was severe hypoglycemia in someone with type 1 diabetes. This identifies a group that may have particular risks with standard therapy, in whom there may be justification for exposing them to the potential side effects of the transplant. That approach changes the risk-benefit ratio – that’s the way I interpret it.
The other exciting piece from this particular study is that it was a multisite project, and they had to do islet isolation at each site under standardized conditions, which is new. If we’re ever going to bring islet transplantation forward as a therapy and have it be approved by the Food and Drug Administration, there must be tremendous standardization in how islets are harvested and prepared for use. The fact that they were able to do that is very exciting.
Dr. Elizabeth R. Seaquist is a professor of medicine and the Pennock Family Chair in Diabetes Research at the University of Minnesota, Minneapolis. She gave these comments in an interview at the meeting. Dr. Seaquist is a colleague of Dr. Hering at the university. She reported financial associations with multiple companies but said none are relevant to this topic.
SAN FRANCISCO – Half of 48 adults with type 1 diabetes, impaired awareness of hypoglycemia, and a history of severe hypoglycemia were able to stop insulin therapy after experimental transplantation of human pancreatic islet cells in a prospective, phase III trial.
The National Institute of Health’s Clinical Islet Transplantation Consortium reported partial, initial results from 365 days of follow-up after islet-cell transplantation in the eight-center study. Speaking for the consortium at the annual scientific sessions of the American Diabetes Association, Dr. Bernhard J. Hering withheld results for the primary outcome measure (the proportion of patients who had a hemoglobin A1c of less than 7% at day 365 and no severe hypoglycemia in days 28 through 365 after the first islet transplant) pending its publication, he said.
Still, results for secondary measures of effectiveness and safety were good enough that "islet transplantation should be considered in this subgroup of patients when other treatment options have failed," said Dr. Hering, a professor of surgery and director of the Islet Cell Transplantation Program at the University of Minnesota, Minneapolis.
The study included patients who had had type 1 diabetes for at least 5 years, with stimulated C-peptide levels below 0.3 ng/mL (considered "absent") and at least one episode of severe hypoglycemia in the prior year with documentation of reduced hypoglycemia awareness and/or marked glycemic lability, if they didn’t meet any of 32 exclusion criteria. All patients underwent immunosuppression as part of the transplantation protocol.
Of the 48 patients, 26 received a second islet cell transplantation, and 1 received a third transplantation. Islet grafts were functioning in more than 90% of patients at day 365 of follow-up, he and his associates reported.
At day 365, roughly 50% of patients were insulin free. Insulin use decreased significantly to a median of 0 unit/kg per day at day 365.
Serum glucose levels and C-peptide secretion during mixed-meal tolerance tests improved over time after transplantation. Clarke scores and Ryan scores to assess patient awareness of hypoglycemia both improved significantly by day 365, as did measures of the glycemic lability index and the mean amplitude of glycemic excursions.
The median percentage of time spent within the desired glucose range increased from about 50% at baseline to nearly 95% at day 365, Dr. Hering reported.
The 19 serious adverse events included 5 that were procedure related (bleeding after percutaneous cannulation of a portal vein), 13 transient events related to immunosuppression (neutropenia, cytokine release, or elevated liver function test results), and 1 episode of hypoglycemia in a patient on insulin. None of these events caused death, disability, or permanent sequelae. Among other adverse events, a small but statistically significant drop in glomerular function test results was associated with the start of immunosuppression, six patients had calculated panel reactive antibodies above zero, and one patient developed acute kidney injury for unclear reasons.
The investigators plan further long-term follow-up.
Registry data suggest that approximately 35% of U.S. patients with type 1 diabetes each year report severe hypoglycemia requiring assistance, Dr. Hering said.
Dr. Hering has been a consultant for Novartis, Janssen, Novo Nordisk, Otsuka, and Sanofi.
On Twitter @sherryboschert
SAN FRANCISCO – Half of 48 adults with type 1 diabetes, impaired awareness of hypoglycemia, and a history of severe hypoglycemia were able to stop insulin therapy after experimental transplantation of human pancreatic islet cells in a prospective, phase III trial.
The National Institute of Health’s Clinical Islet Transplantation Consortium reported partial, initial results from 365 days of follow-up after islet-cell transplantation in the eight-center study. Speaking for the consortium at the annual scientific sessions of the American Diabetes Association, Dr. Bernhard J. Hering withheld results for the primary outcome measure (the proportion of patients who had a hemoglobin A1c of less than 7% at day 365 and no severe hypoglycemia in days 28 through 365 after the first islet transplant) pending its publication, he said.
Still, results for secondary measures of effectiveness and safety were good enough that "islet transplantation should be considered in this subgroup of patients when other treatment options have failed," said Dr. Hering, a professor of surgery and director of the Islet Cell Transplantation Program at the University of Minnesota, Minneapolis.
The study included patients who had had type 1 diabetes for at least 5 years, with stimulated C-peptide levels below 0.3 ng/mL (considered "absent") and at least one episode of severe hypoglycemia in the prior year with documentation of reduced hypoglycemia awareness and/or marked glycemic lability, if they didn’t meet any of 32 exclusion criteria. All patients underwent immunosuppression as part of the transplantation protocol.
Of the 48 patients, 26 received a second islet cell transplantation, and 1 received a third transplantation. Islet grafts were functioning in more than 90% of patients at day 365 of follow-up, he and his associates reported.
At day 365, roughly 50% of patients were insulin free. Insulin use decreased significantly to a median of 0 unit/kg per day at day 365.
Serum glucose levels and C-peptide secretion during mixed-meal tolerance tests improved over time after transplantation. Clarke scores and Ryan scores to assess patient awareness of hypoglycemia both improved significantly by day 365, as did measures of the glycemic lability index and the mean amplitude of glycemic excursions.
The median percentage of time spent within the desired glucose range increased from about 50% at baseline to nearly 95% at day 365, Dr. Hering reported.
The 19 serious adverse events included 5 that were procedure related (bleeding after percutaneous cannulation of a portal vein), 13 transient events related to immunosuppression (neutropenia, cytokine release, or elevated liver function test results), and 1 episode of hypoglycemia in a patient on insulin. None of these events caused death, disability, or permanent sequelae. Among other adverse events, a small but statistically significant drop in glomerular function test results was associated with the start of immunosuppression, six patients had calculated panel reactive antibodies above zero, and one patient developed acute kidney injury for unclear reasons.
The investigators plan further long-term follow-up.
Registry data suggest that approximately 35% of U.S. patients with type 1 diabetes each year report severe hypoglycemia requiring assistance, Dr. Hering said.
Dr. Hering has been a consultant for Novartis, Janssen, Novo Nordisk, Otsuka, and Sanofi.
On Twitter @sherryboschert
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: You’ll have to wait for the primary results, but secondary outcomes suggest success with islet-cell transplantation in a subset of patients with type 1 diabetes.
Major finding: Half of patients were able to stop insulin within a year of transplantation.
Data source: A prospective, open-label, single-arm study of islet-cell transplantation in 48 adults with type 1 diabetes and a history of severe hypoglycemia and hypoglycemia unawareness.
Disclosures: Dr. Hering has been a consultant for Novartis, Janssen, Novo Nordisk, Otsuka, and Sanofi.
DPPOS: Metformin showed no effect on cognition
SAN FRANCISCO – There appear to be no effects on cognition from participating in the lifestyle and metformin arms of the Diabetes Prevention Program Outcomes Study, results from a large long-term analysis showed.
Diabetes was not related to cognition, but a worse hemoglobin A1c level was associated with a worse cognitive performance, Dr. José A. Luchsinger said at the annual scientific sessions of the American Diabetes Association. "Importantly, metformin is safe from a cognitive standpoint, contrary to some recent reports."
The Diabetes Prevention Program Outcomes Study (DPPOS) is a follow-up to the Diabetes Prevention Program (DPP), a randomized clinical trial that compared intensive lifestyle and metformin with placebo for the prevention of diabetes. On behalf of the DPP Research Group, Dr. Luchsinger presented findings from a study that set out to determine if the delay in or prevention of diabetes translated into cognitive benefits 12 years after randomization into the DPP.
"Diabetes in middle age and old age is related to cognitive impairment, both in amnestic and nonamnestic domains, and also in a range of severity from mild cognitive impairment to dementia," said Dr. Luchsinger of the department of medicine at Columbia University Medical Center, New York. "This association extends to the continuum of dysglycemia."
He and his associates hypothesized that diabetes prevention with metformin and lifestyle changes would be associated with better cognitive performance in the DPPOS. Their secondary hypotheses were that diabetes and dysglycemia are associated with worse cognitive function, and that metformin exposure is not associated with cognitive impairment. The researchers conducted cognitive assessments 12 and 14 years after DPP randomization. Global cognition was assessed with the six-item screener of the Mini-Mental State Exam, memory with the Spanish English Verbal Learning Test (SEVLT), and frontal executive function with an animal fluency (AF) and a letter fluency (LF) test and the Digit Symbol Substitution Test (DSST). They also calculated a composite of the SEVLT, AF, LF, and DSST results.
In all, 2,331 participated in the cognitive assessments. Their mean age was 64 years and 68% were women. There were no significant baseline differences in demographic and clinical characteristics by randomization group, but HbA1c level, diabetes prevalence, and diabetes duration were lower in the lifestyle and metformin groups.
Dr. Luchsinger reported that cognition was similar across all DPP treatment arms in year 8, while SEVLT improved from year 8 to year 10 in all arms (P = .0001). Changes in cognition were similar across DPP arms, but a worse HbA1c level was associated with a worse cognition composite score in models adjusted for age at randomization and assessment year (P = .0002). Exposure to metformin was not related to worse cognition.
"It’s important to consider that all DPP participants had impaired glucose tolerance at baseline," Dr. Luchsinger noted. "We had no people with normal glucose tolerance to compare them to; all had a high risk for developing diabetes. Also, the cohort is just entering the age of susceptibility of cognitive impairment. It may be that following them in older ages may show differences that we’re not seeing right now. A legacy effect is possible. By that I mean that there may be a long lag time from the intervention to cognitive effects."
The researchers plan to conduct a longer follow-up of the cohort with an assessment of brain structure function and amyloid load.
The study was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Veterans Affairs, the Indian Health Service, Bristol-Myers Squibb, Parke Davis, Lipha, and Lifescan. Dr. Luchsinger said he had no relevant financial conflicts.
On Twitter @dougbrunk
SAN FRANCISCO – There appear to be no effects on cognition from participating in the lifestyle and metformin arms of the Diabetes Prevention Program Outcomes Study, results from a large long-term analysis showed.
Diabetes was not related to cognition, but a worse hemoglobin A1c level was associated with a worse cognitive performance, Dr. José A. Luchsinger said at the annual scientific sessions of the American Diabetes Association. "Importantly, metformin is safe from a cognitive standpoint, contrary to some recent reports."
The Diabetes Prevention Program Outcomes Study (DPPOS) is a follow-up to the Diabetes Prevention Program (DPP), a randomized clinical trial that compared intensive lifestyle and metformin with placebo for the prevention of diabetes. On behalf of the DPP Research Group, Dr. Luchsinger presented findings from a study that set out to determine if the delay in or prevention of diabetes translated into cognitive benefits 12 years after randomization into the DPP.
"Diabetes in middle age and old age is related to cognitive impairment, both in amnestic and nonamnestic domains, and also in a range of severity from mild cognitive impairment to dementia," said Dr. Luchsinger of the department of medicine at Columbia University Medical Center, New York. "This association extends to the continuum of dysglycemia."
He and his associates hypothesized that diabetes prevention with metformin and lifestyle changes would be associated with better cognitive performance in the DPPOS. Their secondary hypotheses were that diabetes and dysglycemia are associated with worse cognitive function, and that metformin exposure is not associated with cognitive impairment. The researchers conducted cognitive assessments 12 and 14 years after DPP randomization. Global cognition was assessed with the six-item screener of the Mini-Mental State Exam, memory with the Spanish English Verbal Learning Test (SEVLT), and frontal executive function with an animal fluency (AF) and a letter fluency (LF) test and the Digit Symbol Substitution Test (DSST). They also calculated a composite of the SEVLT, AF, LF, and DSST results.
In all, 2,331 participated in the cognitive assessments. Their mean age was 64 years and 68% were women. There were no significant baseline differences in demographic and clinical characteristics by randomization group, but HbA1c level, diabetes prevalence, and diabetes duration were lower in the lifestyle and metformin groups.
Dr. Luchsinger reported that cognition was similar across all DPP treatment arms in year 8, while SEVLT improved from year 8 to year 10 in all arms (P = .0001). Changes in cognition were similar across DPP arms, but a worse HbA1c level was associated with a worse cognition composite score in models adjusted for age at randomization and assessment year (P = .0002). Exposure to metformin was not related to worse cognition.
"It’s important to consider that all DPP participants had impaired glucose tolerance at baseline," Dr. Luchsinger noted. "We had no people with normal glucose tolerance to compare them to; all had a high risk for developing diabetes. Also, the cohort is just entering the age of susceptibility of cognitive impairment. It may be that following them in older ages may show differences that we’re not seeing right now. A legacy effect is possible. By that I mean that there may be a long lag time from the intervention to cognitive effects."
The researchers plan to conduct a longer follow-up of the cohort with an assessment of brain structure function and amyloid load.
The study was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Veterans Affairs, the Indian Health Service, Bristol-Myers Squibb, Parke Davis, Lipha, and Lifescan. Dr. Luchsinger said he had no relevant financial conflicts.
On Twitter @dougbrunk
SAN FRANCISCO – There appear to be no effects on cognition from participating in the lifestyle and metformin arms of the Diabetes Prevention Program Outcomes Study, results from a large long-term analysis showed.
Diabetes was not related to cognition, but a worse hemoglobin A1c level was associated with a worse cognitive performance, Dr. José A. Luchsinger said at the annual scientific sessions of the American Diabetes Association. "Importantly, metformin is safe from a cognitive standpoint, contrary to some recent reports."
The Diabetes Prevention Program Outcomes Study (DPPOS) is a follow-up to the Diabetes Prevention Program (DPP), a randomized clinical trial that compared intensive lifestyle and metformin with placebo for the prevention of diabetes. On behalf of the DPP Research Group, Dr. Luchsinger presented findings from a study that set out to determine if the delay in or prevention of diabetes translated into cognitive benefits 12 years after randomization into the DPP.
"Diabetes in middle age and old age is related to cognitive impairment, both in amnestic and nonamnestic domains, and also in a range of severity from mild cognitive impairment to dementia," said Dr. Luchsinger of the department of medicine at Columbia University Medical Center, New York. "This association extends to the continuum of dysglycemia."
He and his associates hypothesized that diabetes prevention with metformin and lifestyle changes would be associated with better cognitive performance in the DPPOS. Their secondary hypotheses were that diabetes and dysglycemia are associated with worse cognitive function, and that metformin exposure is not associated with cognitive impairment. The researchers conducted cognitive assessments 12 and 14 years after DPP randomization. Global cognition was assessed with the six-item screener of the Mini-Mental State Exam, memory with the Spanish English Verbal Learning Test (SEVLT), and frontal executive function with an animal fluency (AF) and a letter fluency (LF) test and the Digit Symbol Substitution Test (DSST). They also calculated a composite of the SEVLT, AF, LF, and DSST results.
In all, 2,331 participated in the cognitive assessments. Their mean age was 64 years and 68% were women. There were no significant baseline differences in demographic and clinical characteristics by randomization group, but HbA1c level, diabetes prevalence, and diabetes duration were lower in the lifestyle and metformin groups.
Dr. Luchsinger reported that cognition was similar across all DPP treatment arms in year 8, while SEVLT improved from year 8 to year 10 in all arms (P = .0001). Changes in cognition were similar across DPP arms, but a worse HbA1c level was associated with a worse cognition composite score in models adjusted for age at randomization and assessment year (P = .0002). Exposure to metformin was not related to worse cognition.
"It’s important to consider that all DPP participants had impaired glucose tolerance at baseline," Dr. Luchsinger noted. "We had no people with normal glucose tolerance to compare them to; all had a high risk for developing diabetes. Also, the cohort is just entering the age of susceptibility of cognitive impairment. It may be that following them in older ages may show differences that we’re not seeing right now. A legacy effect is possible. By that I mean that there may be a long lag time from the intervention to cognitive effects."
The researchers plan to conduct a longer follow-up of the cohort with an assessment of brain structure function and amyloid load.
The study was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Veterans Affairs, the Indian Health Service, Bristol-Myers Squibb, Parke Davis, Lipha, and Lifescan. Dr. Luchsinger said he had no relevant financial conflicts.
On Twitter @dougbrunk
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: On long-term follow-up, there appear to be no cognitive differences among the treatment arms of the DPPOS.
Major finding: At year 8 of follow-up, cognition was similar among participants in the lifestyle and metformin arms of DPPOS.
Data source: A total of 2,331 cognitive assessments in the lifestyle and metformin arms of DPPOS.
Disclosures: The study was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Veterans Affairs, the Indian Health Service, Bristol-Myers Squibb, Parke Davis, Lipha, and Lifescan. Dr. Luchsinger said he had no relevant financial conflicts.
USPSTF: Offer behavioral counseling to prevent cardiovascular disease
Overweight or obese adults at risk for cardiovascular disease should receive intensive behavioral counseling interventions, according to a recommendation statement by the U. S. Preventive Services Task Force.
After a comprehensive review of the current literature, the USPSTF concluded "with moderate certainty" that interventions promoting a healthful diet and increased physical activity have a moderate net benefit in this patient population, said Dr. Michael L. LeFevre, chair of the task force at the time the recommendation was finalized, and professor of family medicine at the University of Missouri, Columbia.
The recommendation statement issued Aug. 25 is "an update and refinement" of the 2003 USPSTF recommendation on dietary counseling for at-risk adults, this time targeting overweight or obese patients who have additional CVD risk factors such as hypertension, dyslipidemia, impaired fasting glucose, or metabolic syndrome.
The group reviewed 74 trials assessing the effectiveness of behavioral counseling interventions of various intensities. Only 16 reported on direct health outcomes such as CVD events, mortality, or quality of life, the task force noted, so there is inadequate evidence about intensive behavioral counseling’s effect on such outcomes.
A total of 71 trials involving more than 32,000 participants focused on intermediate health outcomes such as lipid levels, blood pressure, glucose levels, weight, and medication use. Overall, intensive counseling interventions made "small but important changes" in these outcomes, with total cholesterol levels decreasing approximately 3-6 mg/dL, LDL cholesterol decreasing by 1.5-5.0 mg/dL, systolic blood pressure decreasing by 1-3 mm Hg, diastolic blood pressure decreasing by 1-2 mm Hg, and fasting glucose levels decreasing by 1-3 mg/dL.
In addition, weight decreased by a mean of approximately 3 kg, and the proportion of patients who participated in moderate-intensity exercise for 150 minutes per week rose from 10% to 25%. However, few of these studies followed patients for more than 1-2 years, so the evidence was inadequate to assess longer-term benefits.
Because very few and mostly minor adverse events were associated with these interventions, they yielded a moderate net benefit.
Most of the intensive behavioral counseling interventions that were assessed averaged 5-16 individual or group sessions during a period of 9-12 months. All included didactic education; in most programs, specially trained professionals (dietitians, nutritionists, physiotherapists, exercise professionals, health educators, and psychologists) provided monitoring and feedback for the participants, devised individualized care plans, and taught problem-solving skills. Many types and combinations of interventions were effective, and almost all were delivered outside the primary care setting.
The recommendation statement is in line with others published by the American Heart Association, the American College of Sports Medicine, and the American Academy of Family Physicians. The AAFP is updating its recommendations regarding behavioral counseling to prevent CVD, Dr. LeFevre and his associates noted.
The USPSTF, funded by but independent of the federal government, makes recommendations about the effectiveness of specific preventive-care services based on evidence of benefits and harms, without considering costs.
Do you refer overweight or obese patients with cardiovascular risk factors for intensive behavioral counseling? Take our Quick Poll on the Family Practice News homepage.
Overweight or obese adults at risk for cardiovascular disease should receive intensive behavioral counseling interventions, according to a recommendation statement by the U. S. Preventive Services Task Force.
After a comprehensive review of the current literature, the USPSTF concluded "with moderate certainty" that interventions promoting a healthful diet and increased physical activity have a moderate net benefit in this patient population, said Dr. Michael L. LeFevre, chair of the task force at the time the recommendation was finalized, and professor of family medicine at the University of Missouri, Columbia.
The recommendation statement issued Aug. 25 is "an update and refinement" of the 2003 USPSTF recommendation on dietary counseling for at-risk adults, this time targeting overweight or obese patients who have additional CVD risk factors such as hypertension, dyslipidemia, impaired fasting glucose, or metabolic syndrome.
The group reviewed 74 trials assessing the effectiveness of behavioral counseling interventions of various intensities. Only 16 reported on direct health outcomes such as CVD events, mortality, or quality of life, the task force noted, so there is inadequate evidence about intensive behavioral counseling’s effect on such outcomes.
A total of 71 trials involving more than 32,000 participants focused on intermediate health outcomes such as lipid levels, blood pressure, glucose levels, weight, and medication use. Overall, intensive counseling interventions made "small but important changes" in these outcomes, with total cholesterol levels decreasing approximately 3-6 mg/dL, LDL cholesterol decreasing by 1.5-5.0 mg/dL, systolic blood pressure decreasing by 1-3 mm Hg, diastolic blood pressure decreasing by 1-2 mm Hg, and fasting glucose levels decreasing by 1-3 mg/dL.
In addition, weight decreased by a mean of approximately 3 kg, and the proportion of patients who participated in moderate-intensity exercise for 150 minutes per week rose from 10% to 25%. However, few of these studies followed patients for more than 1-2 years, so the evidence was inadequate to assess longer-term benefits.
Because very few and mostly minor adverse events were associated with these interventions, they yielded a moderate net benefit.
Most of the intensive behavioral counseling interventions that were assessed averaged 5-16 individual or group sessions during a period of 9-12 months. All included didactic education; in most programs, specially trained professionals (dietitians, nutritionists, physiotherapists, exercise professionals, health educators, and psychologists) provided monitoring and feedback for the participants, devised individualized care plans, and taught problem-solving skills. Many types and combinations of interventions were effective, and almost all were delivered outside the primary care setting.
The recommendation statement is in line with others published by the American Heart Association, the American College of Sports Medicine, and the American Academy of Family Physicians. The AAFP is updating its recommendations regarding behavioral counseling to prevent CVD, Dr. LeFevre and his associates noted.
The USPSTF, funded by but independent of the federal government, makes recommendations about the effectiveness of specific preventive-care services based on evidence of benefits and harms, without considering costs.
Do you refer overweight or obese patients with cardiovascular risk factors for intensive behavioral counseling? Take our Quick Poll on the Family Practice News homepage.
Overweight or obese adults at risk for cardiovascular disease should receive intensive behavioral counseling interventions, according to a recommendation statement by the U. S. Preventive Services Task Force.
After a comprehensive review of the current literature, the USPSTF concluded "with moderate certainty" that interventions promoting a healthful diet and increased physical activity have a moderate net benefit in this patient population, said Dr. Michael L. LeFevre, chair of the task force at the time the recommendation was finalized, and professor of family medicine at the University of Missouri, Columbia.
The recommendation statement issued Aug. 25 is "an update and refinement" of the 2003 USPSTF recommendation on dietary counseling for at-risk adults, this time targeting overweight or obese patients who have additional CVD risk factors such as hypertension, dyslipidemia, impaired fasting glucose, or metabolic syndrome.
The group reviewed 74 trials assessing the effectiveness of behavioral counseling interventions of various intensities. Only 16 reported on direct health outcomes such as CVD events, mortality, or quality of life, the task force noted, so there is inadequate evidence about intensive behavioral counseling’s effect on such outcomes.
A total of 71 trials involving more than 32,000 participants focused on intermediate health outcomes such as lipid levels, blood pressure, glucose levels, weight, and medication use. Overall, intensive counseling interventions made "small but important changes" in these outcomes, with total cholesterol levels decreasing approximately 3-6 mg/dL, LDL cholesterol decreasing by 1.5-5.0 mg/dL, systolic blood pressure decreasing by 1-3 mm Hg, diastolic blood pressure decreasing by 1-2 mm Hg, and fasting glucose levels decreasing by 1-3 mg/dL.
In addition, weight decreased by a mean of approximately 3 kg, and the proportion of patients who participated in moderate-intensity exercise for 150 minutes per week rose from 10% to 25%. However, few of these studies followed patients for more than 1-2 years, so the evidence was inadequate to assess longer-term benefits.
Because very few and mostly minor adverse events were associated with these interventions, they yielded a moderate net benefit.
Most of the intensive behavioral counseling interventions that were assessed averaged 5-16 individual or group sessions during a period of 9-12 months. All included didactic education; in most programs, specially trained professionals (dietitians, nutritionists, physiotherapists, exercise professionals, health educators, and psychologists) provided monitoring and feedback for the participants, devised individualized care plans, and taught problem-solving skills. Many types and combinations of interventions were effective, and almost all were delivered outside the primary care setting.
The recommendation statement is in line with others published by the American Heart Association, the American College of Sports Medicine, and the American Academy of Family Physicians. The AAFP is updating its recommendations regarding behavioral counseling to prevent CVD, Dr. LeFevre and his associates noted.
The USPSTF, funded by but independent of the federal government, makes recommendations about the effectiveness of specific preventive-care services based on evidence of benefits and harms, without considering costs.
Do you refer overweight or obese patients with cardiovascular risk factors for intensive behavioral counseling? Take our Quick Poll on the Family Practice News homepage.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point: Refer overweight or obese patients at risk of cardiovascular disease for intensive behavioral counseling.
Major Finding: Intensive behavioral counseling interventions made small but important changes in several intermediate health outcomes, with total cholesterol levels decreasing by about 3-6 mg/dL, LDL cholesterol decreasing by 1.5-5.0 mg/dL, systolic blood pressure decreasing by 1-3 mm Hg, diastolic blood pressure decreasing by 1-2 mm Hg, fasting glucose levels decreasing by 1-3 mg/dL, and weight decreasing by a mean of 3 kg.
Data Source: An update and refinement of a 2003 USPSTF recommendation on dietary counseling for overweight/obese adults who have additional risk factors for CVD, based on a comprehensive review of the literature.
Disclosures: The USPSTF, funded by but independent of the federal government, makes recommendations about the effectiveness of specific preventive-care services based on evidence of benefits and harms, without considering costs.
Lilly’s insulin glargine tentatively approved, pending patent litigation
The Food and Drug Administration has granted a "tentative" approval to the insulin glargine product developed by Boehringer Ingelheim Pharmaceuticals and Eli Lilly, according to an announcement by the companies issued Aug. 18.
The indication for the basal insulin, which has the trade name Basaglar, is to improve glycemic control in adults with type 2 diabetes and in combination with mealtime insulin in adult and pediatric patients with type 1 diabetes.
"With a tentative approval, the FDA has determined that Basaglar meets all of the regulatory requirements for approval, but it is subject to an automatic stay of up to 30 months as a result of litigation filed by Sanofi, claiming patent infringement," the Lilly statement says. Under the Drug Price Competition and Patent Term Restoration Act (the Hatch-Waxman act), "the FDA cannot give final approval until the end of the 30-month period in mid-2016, unless the court finds in favor of Lilly earlier," according to the statement.
The statement says that Basaglar "has the same amino acid sequence as the currently marketed insulin glargine product."
In Europe, where the product is considered a biosimilar, the Committee for Medicinal Products for Human Use (CHMP), has issued a positive recommendation for this product. The CHMP is a division of the European Medicines Agency, the equivalent of the FDA; the EMA defines a biosimilar as "a biological medicine that is similar to another biological medicine" that has already been authorized for use in Europe.
Sanofi’s insulin glargine was approved in 2000 and is marketed as Lantus.
The Food and Drug Administration has granted a "tentative" approval to the insulin glargine product developed by Boehringer Ingelheim Pharmaceuticals and Eli Lilly, according to an announcement by the companies issued Aug. 18.
The indication for the basal insulin, which has the trade name Basaglar, is to improve glycemic control in adults with type 2 diabetes and in combination with mealtime insulin in adult and pediatric patients with type 1 diabetes.
"With a tentative approval, the FDA has determined that Basaglar meets all of the regulatory requirements for approval, but it is subject to an automatic stay of up to 30 months as a result of litigation filed by Sanofi, claiming patent infringement," the Lilly statement says. Under the Drug Price Competition and Patent Term Restoration Act (the Hatch-Waxman act), "the FDA cannot give final approval until the end of the 30-month period in mid-2016, unless the court finds in favor of Lilly earlier," according to the statement.
The statement says that Basaglar "has the same amino acid sequence as the currently marketed insulin glargine product."
In Europe, where the product is considered a biosimilar, the Committee for Medicinal Products for Human Use (CHMP), has issued a positive recommendation for this product. The CHMP is a division of the European Medicines Agency, the equivalent of the FDA; the EMA defines a biosimilar as "a biological medicine that is similar to another biological medicine" that has already been authorized for use in Europe.
Sanofi’s insulin glargine was approved in 2000 and is marketed as Lantus.
The Food and Drug Administration has granted a "tentative" approval to the insulin glargine product developed by Boehringer Ingelheim Pharmaceuticals and Eli Lilly, according to an announcement by the companies issued Aug. 18.
The indication for the basal insulin, which has the trade name Basaglar, is to improve glycemic control in adults with type 2 diabetes and in combination with mealtime insulin in adult and pediatric patients with type 1 diabetes.
"With a tentative approval, the FDA has determined that Basaglar meets all of the regulatory requirements for approval, but it is subject to an automatic stay of up to 30 months as a result of litigation filed by Sanofi, claiming patent infringement," the Lilly statement says. Under the Drug Price Competition and Patent Term Restoration Act (the Hatch-Waxman act), "the FDA cannot give final approval until the end of the 30-month period in mid-2016, unless the court finds in favor of Lilly earlier," according to the statement.
The statement says that Basaglar "has the same amino acid sequence as the currently marketed insulin glargine product."
In Europe, where the product is considered a biosimilar, the Committee for Medicinal Products for Human Use (CHMP), has issued a positive recommendation for this product. The CHMP is a division of the European Medicines Agency, the equivalent of the FDA; the EMA defines a biosimilar as "a biological medicine that is similar to another biological medicine" that has already been authorized for use in Europe.
Sanofi’s insulin glargine was approved in 2000 and is marketed as Lantus.
