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Dulaglutide OK for primary, secondary CV risk reduction in U.S.
The US Food and Drug Administration (FDA) has additionally approved dulaglutide (Trulicity) for reducing the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes with and without established cardiovascular disease (CVD) or multiple CV risk factors, the company has announced.
Dulaglutide is a once-weekly injectable glucagonlike peptide-1 (GLP-1) receptor agonist first approved in the United States in 2014 for the treatment of type 2 diabetes.
It is now the first and only type 2 diabetes medicine approved to reduce the risk of CV events for both primary and secondary prevention populations. The European Medicines Agency approved a similar indication for dulaglutide last fall.
The new US indication is based on results of the CV outcomes trial for dulaglutide, known as REWIND, which was the longest-running CV outcomes trial in the GLP-1 agonist class.
Chair of the REWIND study, Hertzel Gerstein, MD, professor of medicine at McMaster University and Hamilton Health Sciences, Ontario, Canada, said in a Lilly statement that the trial included a “broad population of people living with type 2 diabetes, reflective of those in the general population. We therefore assessed the effect of Trulicity in people with established CVD as well as those with multiple CV risk factors.”
“Globally, over 415 million people have type 2 diabetes, which is itself a CV risk factor. However, only about one third have established CVD, which is why this new indication, and the supporting evidence, is important for the millions of people in the United States living with diabetes,” he added.
Other GLP-1 agonists have been granted approvals for additional reduction of CV events in patients with type 2 diabetes, but only for secondary prevention.
Most recently the FDA expanded the indication for once-weekly semaglutide to include reducing the risk for MACE, including CV death, nonfatal myocardial infarction, or nonfatal stroke, in adults with type 2 diabetes who have established CVD.
Additional approval based on REWIND trial
The REWIND trial included primarily people with type 2 diabetes without established CVD. The full study results were presented at the 2019 American Diabetes Association Scientific Sessions.
REWIND showed a significant reduction in risk of MACE – a composite endpoint of nonfatal myocardial infarction, nonfatal stroke, or CV death – which occurred in 12.0% of patients in the dulaglutide group, compared with 13.4% of patients in the placebo group, for a risk reduction of 0.88 (95% confidence interval, 0.79-0.99; P = .026), which was consistent across subgroups.
All three components of the MACE primary endpoint showed a reduction with dulaglutide, compared with placebo, including CV death (hazard ratio, 0.91; 95% CI, 0.78-1.06) and nonfatal MI (HR, 0.96; 95% CI, 0.79-1.16), with the strongest and only significant effect seen in nonfatal stroke (HR, 0.76; 95% CI, 0.61-0.95).
No difference was seen between groups in hospital admissions for heart failure.
Dulaglutide was also found to modestly reduce weight by around 1.5 kg (P = .0001) and systolic blood pressure by 1.7 mm Hg (P = .0001).
The safety profile of dulaglutide in REWIND was consistent with other members of the GLP-1 agonist class, with gastrointestinal events being the most common adverse event leading to discontinuation.
Sherry Martin, MD, Lilly’s vice president, medical affairs, noted in the company statement: “For the first time, health care providers can prescribe a diabetes medicine proven to significantly reduce the risk of experiencing a CV event for people with type 2 diabetes with and without established CVD.”
“Trulicity can help people achieve their A1C goals and protect them from experiencing a CV event with a once-weekly, easy-to-use treatment option,” added Martin.
This article first appeared on Medscape.com.
The US Food and Drug Administration (FDA) has additionally approved dulaglutide (Trulicity) for reducing the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes with and without established cardiovascular disease (CVD) or multiple CV risk factors, the company has announced.
Dulaglutide is a once-weekly injectable glucagonlike peptide-1 (GLP-1) receptor agonist first approved in the United States in 2014 for the treatment of type 2 diabetes.
It is now the first and only type 2 diabetes medicine approved to reduce the risk of CV events for both primary and secondary prevention populations. The European Medicines Agency approved a similar indication for dulaglutide last fall.
The new US indication is based on results of the CV outcomes trial for dulaglutide, known as REWIND, which was the longest-running CV outcomes trial in the GLP-1 agonist class.
Chair of the REWIND study, Hertzel Gerstein, MD, professor of medicine at McMaster University and Hamilton Health Sciences, Ontario, Canada, said in a Lilly statement that the trial included a “broad population of people living with type 2 diabetes, reflective of those in the general population. We therefore assessed the effect of Trulicity in people with established CVD as well as those with multiple CV risk factors.”
“Globally, over 415 million people have type 2 diabetes, which is itself a CV risk factor. However, only about one third have established CVD, which is why this new indication, and the supporting evidence, is important for the millions of people in the United States living with diabetes,” he added.
Other GLP-1 agonists have been granted approvals for additional reduction of CV events in patients with type 2 diabetes, but only for secondary prevention.
Most recently the FDA expanded the indication for once-weekly semaglutide to include reducing the risk for MACE, including CV death, nonfatal myocardial infarction, or nonfatal stroke, in adults with type 2 diabetes who have established CVD.
Additional approval based on REWIND trial
The REWIND trial included primarily people with type 2 diabetes without established CVD. The full study results were presented at the 2019 American Diabetes Association Scientific Sessions.
REWIND showed a significant reduction in risk of MACE – a composite endpoint of nonfatal myocardial infarction, nonfatal stroke, or CV death – which occurred in 12.0% of patients in the dulaglutide group, compared with 13.4% of patients in the placebo group, for a risk reduction of 0.88 (95% confidence interval, 0.79-0.99; P = .026), which was consistent across subgroups.
All three components of the MACE primary endpoint showed a reduction with dulaglutide, compared with placebo, including CV death (hazard ratio, 0.91; 95% CI, 0.78-1.06) and nonfatal MI (HR, 0.96; 95% CI, 0.79-1.16), with the strongest and only significant effect seen in nonfatal stroke (HR, 0.76; 95% CI, 0.61-0.95).
No difference was seen between groups in hospital admissions for heart failure.
Dulaglutide was also found to modestly reduce weight by around 1.5 kg (P = .0001) and systolic blood pressure by 1.7 mm Hg (P = .0001).
The safety profile of dulaglutide in REWIND was consistent with other members of the GLP-1 agonist class, with gastrointestinal events being the most common adverse event leading to discontinuation.
Sherry Martin, MD, Lilly’s vice president, medical affairs, noted in the company statement: “For the first time, health care providers can prescribe a diabetes medicine proven to significantly reduce the risk of experiencing a CV event for people with type 2 diabetes with and without established CVD.”
“Trulicity can help people achieve their A1C goals and protect them from experiencing a CV event with a once-weekly, easy-to-use treatment option,” added Martin.
This article first appeared on Medscape.com.
The US Food and Drug Administration (FDA) has additionally approved dulaglutide (Trulicity) for reducing the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes with and without established cardiovascular disease (CVD) or multiple CV risk factors, the company has announced.
Dulaglutide is a once-weekly injectable glucagonlike peptide-1 (GLP-1) receptor agonist first approved in the United States in 2014 for the treatment of type 2 diabetes.
It is now the first and only type 2 diabetes medicine approved to reduce the risk of CV events for both primary and secondary prevention populations. The European Medicines Agency approved a similar indication for dulaglutide last fall.
The new US indication is based on results of the CV outcomes trial for dulaglutide, known as REWIND, which was the longest-running CV outcomes trial in the GLP-1 agonist class.
Chair of the REWIND study, Hertzel Gerstein, MD, professor of medicine at McMaster University and Hamilton Health Sciences, Ontario, Canada, said in a Lilly statement that the trial included a “broad population of people living with type 2 diabetes, reflective of those in the general population. We therefore assessed the effect of Trulicity in people with established CVD as well as those with multiple CV risk factors.”
“Globally, over 415 million people have type 2 diabetes, which is itself a CV risk factor. However, only about one third have established CVD, which is why this new indication, and the supporting evidence, is important for the millions of people in the United States living with diabetes,” he added.
Other GLP-1 agonists have been granted approvals for additional reduction of CV events in patients with type 2 diabetes, but only for secondary prevention.
Most recently the FDA expanded the indication for once-weekly semaglutide to include reducing the risk for MACE, including CV death, nonfatal myocardial infarction, or nonfatal stroke, in adults with type 2 diabetes who have established CVD.
Additional approval based on REWIND trial
The REWIND trial included primarily people with type 2 diabetes without established CVD. The full study results were presented at the 2019 American Diabetes Association Scientific Sessions.
REWIND showed a significant reduction in risk of MACE – a composite endpoint of nonfatal myocardial infarction, nonfatal stroke, or CV death – which occurred in 12.0% of patients in the dulaglutide group, compared with 13.4% of patients in the placebo group, for a risk reduction of 0.88 (95% confidence interval, 0.79-0.99; P = .026), which was consistent across subgroups.
All three components of the MACE primary endpoint showed a reduction with dulaglutide, compared with placebo, including CV death (hazard ratio, 0.91; 95% CI, 0.78-1.06) and nonfatal MI (HR, 0.96; 95% CI, 0.79-1.16), with the strongest and only significant effect seen in nonfatal stroke (HR, 0.76; 95% CI, 0.61-0.95).
No difference was seen between groups in hospital admissions for heart failure.
Dulaglutide was also found to modestly reduce weight by around 1.5 kg (P = .0001) and systolic blood pressure by 1.7 mm Hg (P = .0001).
The safety profile of dulaglutide in REWIND was consistent with other members of the GLP-1 agonist class, with gastrointestinal events being the most common adverse event leading to discontinuation.
Sherry Martin, MD, Lilly’s vice president, medical affairs, noted in the company statement: “For the first time, health care providers can prescribe a diabetes medicine proven to significantly reduce the risk of experiencing a CV event for people with type 2 diabetes with and without established CVD.”
“Trulicity can help people achieve their A1C goals and protect them from experiencing a CV event with a once-weekly, easy-to-use treatment option,” added Martin.
This article first appeared on Medscape.com.
Genetic risk score may flag post-GDM incidence of type 2 disease
Women who had gestational diabetes mellitus had an increased risk for later type 2 diabetes if they carried certain genetic risk factors for the disease, according to a new analysis in BMJ Open Diabetes Research & Care of data from two independent populations.
A higher genetic risk score (GRS) had a modest association with developing type 2 diabetes, but a healthier diet may mitigate this risk, as Mengying Li, PhD, and her colleagues found for participants in the Nurses’ Health Study and members of the Danish National Birth Cohort who developed gestational diabetes mellitus (GDM).
Of 1,884 white women with a history of GDM in the Nurses’ Health Study II (NHSII), 446 (23.7%) went on to develop type 2 diabetes, and of the 550 women who had GDM in the Danish National Birth Cohort (DNBC), 155 (28.2%) developed the disease. The researchers calculated a GRS for type 2 diabetes for the full cohort. Genome-wide association studies completed in European populations were used to identify 59 single-nucleotide polymorphisms (SNPs) associated with the disease.
Dr. Li, an epidemiologist and postdoctoral researcher at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Md., and her coauthors found that women whose GRS was in the highest quartile had a relative risk of 1.19 for type 2 diabetes. The relative risks for the three lower quartiles were 1.25, 0.97, and 1.00, respectively (P value for trend = .02). For each increase of five risk alleles in the GRS, NHSII participants had a 7% increased risk for type 2 diabetes, and DNBC participants saw a 9% increased risk.
Comparing these findings with other studies looking at genetic risk and type 2 diabetes in the general population, Dr. Li and her coauthors noted that the increase in relative risk for type 2 disease with increase in GRS was actually slightly weaker in the GDM cohort they studied. “The smaller effect size among women with GDM likely reflects an already higher baseline genetic risk for [type 2 diabetes] than the general population, as we have demonstrated,” they explained.
Though 11 individual SNPs had a significant individual association with the risk for type 2 diabetes initially, that association disappeared after correction for a false-discovery rate. Dr. Li and her coinvestigators conducted a sensitivity analysis that included only 42 SNPs that were later definitively associated with type 2 disease and they saw essentially unchanged results.
The researchers also investigated how dietary quality affected the GRS–type 2 diabetes association by dichotomizing self-reported diet quality in both cohorts into healthier diet quality and less healthy diet quality. They found a tighter association between GRS and type 2 diabetes for women with diet quality below the median, whereas women with higher diet quality did not have such a strong association between GRS and type 2 disease. The researchers wrote that there was “suggestive evidence that a healthful diet might mitigate the excessive risk of T2D [type 2 diabetes] related to greater genetic susceptibility, which supports public health efforts of encouraging a healthful diet” for diabetes prevention in this high-risk population.
Patients in the NHSII were followed for a mean 21.3 years, and those in the DNBC were followed for a mean 12.7 years. Mean age at index pregnancy was 30.5 years for the NHSII cohort and 31.7 for the DNBC cohort. In the NHSII cohort, just 8.4% of participants reported smoking before pregnancy, compared with 26.4% of those in the DNBC cohort. The NHSII cohort participants, wrote Dr. Li and her coauthors, “were also less likely to have a family history of diabetes, less likely to smoke, and be leaner than women in the DNBC.”
Dr. Li and her coauthors noted that, “despite being the largest genetic study by far on [type 2 diabetes] among women with GDM, our study may not be sufficiently powered to examine the associations of individual T2D SNPs in relation to the risk of developing T2D.” Another limitation was that for the Danish cohort, information about diet was drawn from a one-time questionnaire administered between 9 and 16 years after the index pregnancy, so full data about dietary quality over time was not available. Also of note is that the study included only white participants, limiting generalizability to women of color. The authors called for expanding this research into more racially diverse populations.
The study was supported by the National Institutes of Health. The authors reported that they had no conflicts of interest.
SOURCE: Li M et al. BMJ Open Diab Res Care. 2020 Feb 13. doi: 10.1136/bmjdrc-2019-000850.
Women who had gestational diabetes mellitus had an increased risk for later type 2 diabetes if they carried certain genetic risk factors for the disease, according to a new analysis in BMJ Open Diabetes Research & Care of data from two independent populations.
A higher genetic risk score (GRS) had a modest association with developing type 2 diabetes, but a healthier diet may mitigate this risk, as Mengying Li, PhD, and her colleagues found for participants in the Nurses’ Health Study and members of the Danish National Birth Cohort who developed gestational diabetes mellitus (GDM).
Of 1,884 white women with a history of GDM in the Nurses’ Health Study II (NHSII), 446 (23.7%) went on to develop type 2 diabetes, and of the 550 women who had GDM in the Danish National Birth Cohort (DNBC), 155 (28.2%) developed the disease. The researchers calculated a GRS for type 2 diabetes for the full cohort. Genome-wide association studies completed in European populations were used to identify 59 single-nucleotide polymorphisms (SNPs) associated with the disease.
Dr. Li, an epidemiologist and postdoctoral researcher at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Md., and her coauthors found that women whose GRS was in the highest quartile had a relative risk of 1.19 for type 2 diabetes. The relative risks for the three lower quartiles were 1.25, 0.97, and 1.00, respectively (P value for trend = .02). For each increase of five risk alleles in the GRS, NHSII participants had a 7% increased risk for type 2 diabetes, and DNBC participants saw a 9% increased risk.
Comparing these findings with other studies looking at genetic risk and type 2 diabetes in the general population, Dr. Li and her coauthors noted that the increase in relative risk for type 2 disease with increase in GRS was actually slightly weaker in the GDM cohort they studied. “The smaller effect size among women with GDM likely reflects an already higher baseline genetic risk for [type 2 diabetes] than the general population, as we have demonstrated,” they explained.
Though 11 individual SNPs had a significant individual association with the risk for type 2 diabetes initially, that association disappeared after correction for a false-discovery rate. Dr. Li and her coinvestigators conducted a sensitivity analysis that included only 42 SNPs that were later definitively associated with type 2 disease and they saw essentially unchanged results.
The researchers also investigated how dietary quality affected the GRS–type 2 diabetes association by dichotomizing self-reported diet quality in both cohorts into healthier diet quality and less healthy diet quality. They found a tighter association between GRS and type 2 diabetes for women with diet quality below the median, whereas women with higher diet quality did not have such a strong association between GRS and type 2 disease. The researchers wrote that there was “suggestive evidence that a healthful diet might mitigate the excessive risk of T2D [type 2 diabetes] related to greater genetic susceptibility, which supports public health efforts of encouraging a healthful diet” for diabetes prevention in this high-risk population.
Patients in the NHSII were followed for a mean 21.3 years, and those in the DNBC were followed for a mean 12.7 years. Mean age at index pregnancy was 30.5 years for the NHSII cohort and 31.7 for the DNBC cohort. In the NHSII cohort, just 8.4% of participants reported smoking before pregnancy, compared with 26.4% of those in the DNBC cohort. The NHSII cohort participants, wrote Dr. Li and her coauthors, “were also less likely to have a family history of diabetes, less likely to smoke, and be leaner than women in the DNBC.”
Dr. Li and her coauthors noted that, “despite being the largest genetic study by far on [type 2 diabetes] among women with GDM, our study may not be sufficiently powered to examine the associations of individual T2D SNPs in relation to the risk of developing T2D.” Another limitation was that for the Danish cohort, information about diet was drawn from a one-time questionnaire administered between 9 and 16 years after the index pregnancy, so full data about dietary quality over time was not available. Also of note is that the study included only white participants, limiting generalizability to women of color. The authors called for expanding this research into more racially diverse populations.
The study was supported by the National Institutes of Health. The authors reported that they had no conflicts of interest.
SOURCE: Li M et al. BMJ Open Diab Res Care. 2020 Feb 13. doi: 10.1136/bmjdrc-2019-000850.
Women who had gestational diabetes mellitus had an increased risk for later type 2 diabetes if they carried certain genetic risk factors for the disease, according to a new analysis in BMJ Open Diabetes Research & Care of data from two independent populations.
A higher genetic risk score (GRS) had a modest association with developing type 2 diabetes, but a healthier diet may mitigate this risk, as Mengying Li, PhD, and her colleagues found for participants in the Nurses’ Health Study and members of the Danish National Birth Cohort who developed gestational diabetes mellitus (GDM).
Of 1,884 white women with a history of GDM in the Nurses’ Health Study II (NHSII), 446 (23.7%) went on to develop type 2 diabetes, and of the 550 women who had GDM in the Danish National Birth Cohort (DNBC), 155 (28.2%) developed the disease. The researchers calculated a GRS for type 2 diabetes for the full cohort. Genome-wide association studies completed in European populations were used to identify 59 single-nucleotide polymorphisms (SNPs) associated with the disease.
Dr. Li, an epidemiologist and postdoctoral researcher at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Md., and her coauthors found that women whose GRS was in the highest quartile had a relative risk of 1.19 for type 2 diabetes. The relative risks for the three lower quartiles were 1.25, 0.97, and 1.00, respectively (P value for trend = .02). For each increase of five risk alleles in the GRS, NHSII participants had a 7% increased risk for type 2 diabetes, and DNBC participants saw a 9% increased risk.
Comparing these findings with other studies looking at genetic risk and type 2 diabetes in the general population, Dr. Li and her coauthors noted that the increase in relative risk for type 2 disease with increase in GRS was actually slightly weaker in the GDM cohort they studied. “The smaller effect size among women with GDM likely reflects an already higher baseline genetic risk for [type 2 diabetes] than the general population, as we have demonstrated,” they explained.
Though 11 individual SNPs had a significant individual association with the risk for type 2 diabetes initially, that association disappeared after correction for a false-discovery rate. Dr. Li and her coinvestigators conducted a sensitivity analysis that included only 42 SNPs that were later definitively associated with type 2 disease and they saw essentially unchanged results.
The researchers also investigated how dietary quality affected the GRS–type 2 diabetes association by dichotomizing self-reported diet quality in both cohorts into healthier diet quality and less healthy diet quality. They found a tighter association between GRS and type 2 diabetes for women with diet quality below the median, whereas women with higher diet quality did not have such a strong association between GRS and type 2 disease. The researchers wrote that there was “suggestive evidence that a healthful diet might mitigate the excessive risk of T2D [type 2 diabetes] related to greater genetic susceptibility, which supports public health efforts of encouraging a healthful diet” for diabetes prevention in this high-risk population.
Patients in the NHSII were followed for a mean 21.3 years, and those in the DNBC were followed for a mean 12.7 years. Mean age at index pregnancy was 30.5 years for the NHSII cohort and 31.7 for the DNBC cohort. In the NHSII cohort, just 8.4% of participants reported smoking before pregnancy, compared with 26.4% of those in the DNBC cohort. The NHSII cohort participants, wrote Dr. Li and her coauthors, “were also less likely to have a family history of diabetes, less likely to smoke, and be leaner than women in the DNBC.”
Dr. Li and her coauthors noted that, “despite being the largest genetic study by far on [type 2 diabetes] among women with GDM, our study may not be sufficiently powered to examine the associations of individual T2D SNPs in relation to the risk of developing T2D.” Another limitation was that for the Danish cohort, information about diet was drawn from a one-time questionnaire administered between 9 and 16 years after the index pregnancy, so full data about dietary quality over time was not available. Also of note is that the study included only white participants, limiting generalizability to women of color. The authors called for expanding this research into more racially diverse populations.
The study was supported by the National Institutes of Health. The authors reported that they had no conflicts of interest.
SOURCE: Li M et al. BMJ Open Diab Res Care. 2020 Feb 13. doi: 10.1136/bmjdrc-2019-000850.
FROM BMJ OPEN DIABETES RESEARCH & CARE
FDA opens the door to biosimilar insulin
The Food and Drug Administration published Feb. 21 in the Federal Register a final rule that transitions insulin and other products from regulation as a drug to a biologic. This will provide manufacturers access to the biosimilars approval pathway and is expected to bring more competition to the insulin market. The move comes as insulin manufacturers continue to get increased scrutiny over the significantly increased pricing of their products in recent years.
The transition was required under a provision of the Biologics Price Competition and Innovation Act of 2009.
The move is expected to have no impact on the distribution of insulin and other products affected by the transition.
“In general, prescribers should continue to prescribe and order insulin and other biological products the same way they did before the transition,” the FDA said in an FAQ on the transition for physicians and other health care workers. “In general, pharmacists should continue to dispense and counsel about insulin and other biological products the same way they did before the transition. Prescribers and pharmacists should ensure their patients understand there are no changes to the product and they should continue to use the product the same way as before the transition.”
Other products affected by the transition include human growth hormone (somatropin), pancrelipase, chorionic gonadotropin, follitropin alfa, and menotropins. Information on all the transitioning products will move from the Orange Book (which lists FDA-approved drug products with therapeutic equivalent evaluations) to the Purple Book (which lists FDA-licensed biological products with reference product exclusivity data and biosimilar/interchangeability evaluations).
The FDA in the FAQ reiterated its commitment to reviewing any applications for these transition products within 12 months of submission.
The Food and Drug Administration published Feb. 21 in the Federal Register a final rule that transitions insulin and other products from regulation as a drug to a biologic. This will provide manufacturers access to the biosimilars approval pathway and is expected to bring more competition to the insulin market. The move comes as insulin manufacturers continue to get increased scrutiny over the significantly increased pricing of their products in recent years.
The transition was required under a provision of the Biologics Price Competition and Innovation Act of 2009.
The move is expected to have no impact on the distribution of insulin and other products affected by the transition.
“In general, prescribers should continue to prescribe and order insulin and other biological products the same way they did before the transition,” the FDA said in an FAQ on the transition for physicians and other health care workers. “In general, pharmacists should continue to dispense and counsel about insulin and other biological products the same way they did before the transition. Prescribers and pharmacists should ensure their patients understand there are no changes to the product and they should continue to use the product the same way as before the transition.”
Other products affected by the transition include human growth hormone (somatropin), pancrelipase, chorionic gonadotropin, follitropin alfa, and menotropins. Information on all the transitioning products will move from the Orange Book (which lists FDA-approved drug products with therapeutic equivalent evaluations) to the Purple Book (which lists FDA-licensed biological products with reference product exclusivity data and biosimilar/interchangeability evaluations).
The FDA in the FAQ reiterated its commitment to reviewing any applications for these transition products within 12 months of submission.
The Food and Drug Administration published Feb. 21 in the Federal Register a final rule that transitions insulin and other products from regulation as a drug to a biologic. This will provide manufacturers access to the biosimilars approval pathway and is expected to bring more competition to the insulin market. The move comes as insulin manufacturers continue to get increased scrutiny over the significantly increased pricing of their products in recent years.
The transition was required under a provision of the Biologics Price Competition and Innovation Act of 2009.
The move is expected to have no impact on the distribution of insulin and other products affected by the transition.
“In general, prescribers should continue to prescribe and order insulin and other biological products the same way they did before the transition,” the FDA said in an FAQ on the transition for physicians and other health care workers. “In general, pharmacists should continue to dispense and counsel about insulin and other biological products the same way they did before the transition. Prescribers and pharmacists should ensure their patients understand there are no changes to the product and they should continue to use the product the same way as before the transition.”
Other products affected by the transition include human growth hormone (somatropin), pancrelipase, chorionic gonadotropin, follitropin alfa, and menotropins. Information on all the transitioning products will move from the Orange Book (which lists FDA-approved drug products with therapeutic equivalent evaluations) to the Purple Book (which lists FDA-licensed biological products with reference product exclusivity data and biosimilar/interchangeability evaluations).
The FDA in the FAQ reiterated its commitment to reviewing any applications for these transition products within 12 months of submission.
Stroke risk tied to diabetic retinopathy may not be modifiable
LOS ANGELES – Evidence continues to mount that diabetic retinopathy predicts elevated risk for stroke.
In a new study with nearly 3,000 people, those with diabetic retinopathy were 60% more likely than others with diabetes to develop an incident stroke over time. Investigators also found that addressing glucose, lipids, and blood pressure levels did not mitigate this risk in this secondary analysis of the ACCORD Eye Study.
“We are not surprised with the finding that diabetic retinopathy increases the risk of stroke — as diabetic retinopathy is common microvascular disease that is an established risk factor for cardiovascular disease,” lead author Ka-Ho Wong, BS, MBA, said in an interview.
However, “we were surprised that none of the trial interventions mitigated this risk, in particular the intensive blood pressure reduction, because hypertension is the most important cause of microvascular disease,” he said. Mr. Wong is clinical research coordinator and lab manager of the de Havenon Lab at the University of Utah Health Hospitals and Clinics in Salt Lake City.
The study findings were released Feb. 12, 2020, in advance of formal presentation at the International Stroke Conference sponsored by the American Heart Association.
Common predictor of vascular disease
Diabetic retinopathy is the most common complication of diabetes mellitus, affecting up to 50% of people living with type 1 and type 2 diabetes. In addition, previous research suggests that macrovascular diabetes complications, including stroke, could share a common or synergistic pathway.
This small vessel damage in the eye also has been linked to an increased risk of adverse cardiac events, including heart failure, as previously reported by Medscape Medical News.
To find out more, Mr. Wong and colleagues analyzed 2,828 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study. They compared the stroke risk between 874 people with diabetic retinopathy and another 1,954 diabetics without this complication. The average age was 62 years and 62% were men.
Diabetic neuropathy at baseline was diagnosed using the Early Treatment Diabetic Retinopathy Study Severity Scale using seven-field stereoscopic fundus photographs.
A total of 117 participants experienced a stroke during a mean follow-up of 5.4 years.
The investigators found that diabetic retinopathy was more common among patients who had a stroke (41%) versus 31% of those without a stroke (P = .016). The link between diabetic retinopathy and stroke remained in an analysis adjusted for multiple factors, including baseline age, gender, race, total cholesterol, A1c, smoking, and more. Risk remained elevated, with a hazard ratio of 1.60 (95% confidence interval, 1.10-2.32; P = .015).
Regarding the potential for modifying this risk, the association was unaffected among participants randomly assigned to the ACCORD glucose intervention (P = .305), lipid intervention (P = .546), or blood pressure intervention (P = .422).
The study was a secondary analysis, so information on stroke type and location were unavailable.
The big picture
“Diabetic retinopathy is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to diabetic retinopathy has larger cardiovascular implications,” the researchers noted.
Despite these findings, the researchers suggest that patients with diabetic retinopathy receive aggressive medical management to try to reduce their stroke risk.
“It’s important for everyone with diabetes to maintain good blood glucose control, and those with established diabetic retinopathy should pay particular attention to meeting all the stroke prevention guidelines that are established by the American Stroke Association,” said Mr. Wong.
“Patients with established diabetic retinopathy should pay particular attention to meeting all stroke prevention guidelines established by the [American Heart Association],” he added.
Mr. Wong and colleagues would like to expand on these findings. Pending grant application and funding support, they propose conducting a prospective, observational trial in stroke patients with baseline diabetic retinopathy. One aim would be to identify the most common mechanisms leading to stroke in this population, “which would have important implications for prevention efforts,” he said.
Consistent Findings
“The results of the study showing that having diabetic retinopathy is also associated with an increase in stroke really isn’t surprising. There have been other studies, population-based studies, done in the past, that have found a similar relationship,” Larry B. Goldstein, MD, said in a video commentary on the findings.
“The results are actually quite consistent with several other studies that have evaluated the same relationship,” added Dr. Goldstein, who is chair of the department of neurology and codirector of the Kentucky Neuroscience Institute, University of Kentucky HealthCare, Lexington.
Mr. Wong and Dr. Goldstein have disclosed no relevant financial relationships. The NIH’s National Institute of Neurological Disorders and Stroke funded the study.
This article first appeared on Medscape.com.
LOS ANGELES – Evidence continues to mount that diabetic retinopathy predicts elevated risk for stroke.
In a new study with nearly 3,000 people, those with diabetic retinopathy were 60% more likely than others with diabetes to develop an incident stroke over time. Investigators also found that addressing glucose, lipids, and blood pressure levels did not mitigate this risk in this secondary analysis of the ACCORD Eye Study.
“We are not surprised with the finding that diabetic retinopathy increases the risk of stroke — as diabetic retinopathy is common microvascular disease that is an established risk factor for cardiovascular disease,” lead author Ka-Ho Wong, BS, MBA, said in an interview.
However, “we were surprised that none of the trial interventions mitigated this risk, in particular the intensive blood pressure reduction, because hypertension is the most important cause of microvascular disease,” he said. Mr. Wong is clinical research coordinator and lab manager of the de Havenon Lab at the University of Utah Health Hospitals and Clinics in Salt Lake City.
The study findings were released Feb. 12, 2020, in advance of formal presentation at the International Stroke Conference sponsored by the American Heart Association.
Common predictor of vascular disease
Diabetic retinopathy is the most common complication of diabetes mellitus, affecting up to 50% of people living with type 1 and type 2 diabetes. In addition, previous research suggests that macrovascular diabetes complications, including stroke, could share a common or synergistic pathway.
This small vessel damage in the eye also has been linked to an increased risk of adverse cardiac events, including heart failure, as previously reported by Medscape Medical News.
To find out more, Mr. Wong and colleagues analyzed 2,828 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study. They compared the stroke risk between 874 people with diabetic retinopathy and another 1,954 diabetics without this complication. The average age was 62 years and 62% were men.
Diabetic neuropathy at baseline was diagnosed using the Early Treatment Diabetic Retinopathy Study Severity Scale using seven-field stereoscopic fundus photographs.
A total of 117 participants experienced a stroke during a mean follow-up of 5.4 years.
The investigators found that diabetic retinopathy was more common among patients who had a stroke (41%) versus 31% of those without a stroke (P = .016). The link between diabetic retinopathy and stroke remained in an analysis adjusted for multiple factors, including baseline age, gender, race, total cholesterol, A1c, smoking, and more. Risk remained elevated, with a hazard ratio of 1.60 (95% confidence interval, 1.10-2.32; P = .015).
Regarding the potential for modifying this risk, the association was unaffected among participants randomly assigned to the ACCORD glucose intervention (P = .305), lipid intervention (P = .546), or blood pressure intervention (P = .422).
The study was a secondary analysis, so information on stroke type and location were unavailable.
The big picture
“Diabetic retinopathy is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to diabetic retinopathy has larger cardiovascular implications,” the researchers noted.
Despite these findings, the researchers suggest that patients with diabetic retinopathy receive aggressive medical management to try to reduce their stroke risk.
“It’s important for everyone with diabetes to maintain good blood glucose control, and those with established diabetic retinopathy should pay particular attention to meeting all the stroke prevention guidelines that are established by the American Stroke Association,” said Mr. Wong.
“Patients with established diabetic retinopathy should pay particular attention to meeting all stroke prevention guidelines established by the [American Heart Association],” he added.
Mr. Wong and colleagues would like to expand on these findings. Pending grant application and funding support, they propose conducting a prospective, observational trial in stroke patients with baseline diabetic retinopathy. One aim would be to identify the most common mechanisms leading to stroke in this population, “which would have important implications for prevention efforts,” he said.
Consistent Findings
“The results of the study showing that having diabetic retinopathy is also associated with an increase in stroke really isn’t surprising. There have been other studies, population-based studies, done in the past, that have found a similar relationship,” Larry B. Goldstein, MD, said in a video commentary on the findings.
“The results are actually quite consistent with several other studies that have evaluated the same relationship,” added Dr. Goldstein, who is chair of the department of neurology and codirector of the Kentucky Neuroscience Institute, University of Kentucky HealthCare, Lexington.
Mr. Wong and Dr. Goldstein have disclosed no relevant financial relationships. The NIH’s National Institute of Neurological Disorders and Stroke funded the study.
This article first appeared on Medscape.com.
LOS ANGELES – Evidence continues to mount that diabetic retinopathy predicts elevated risk for stroke.
In a new study with nearly 3,000 people, those with diabetic retinopathy were 60% more likely than others with diabetes to develop an incident stroke over time. Investigators also found that addressing glucose, lipids, and blood pressure levels did not mitigate this risk in this secondary analysis of the ACCORD Eye Study.
“We are not surprised with the finding that diabetic retinopathy increases the risk of stroke — as diabetic retinopathy is common microvascular disease that is an established risk factor for cardiovascular disease,” lead author Ka-Ho Wong, BS, MBA, said in an interview.
However, “we were surprised that none of the trial interventions mitigated this risk, in particular the intensive blood pressure reduction, because hypertension is the most important cause of microvascular disease,” he said. Mr. Wong is clinical research coordinator and lab manager of the de Havenon Lab at the University of Utah Health Hospitals and Clinics in Salt Lake City.
The study findings were released Feb. 12, 2020, in advance of formal presentation at the International Stroke Conference sponsored by the American Heart Association.
Common predictor of vascular disease
Diabetic retinopathy is the most common complication of diabetes mellitus, affecting up to 50% of people living with type 1 and type 2 diabetes. In addition, previous research suggests that macrovascular diabetes complications, including stroke, could share a common or synergistic pathway.
This small vessel damage in the eye also has been linked to an increased risk of adverse cardiac events, including heart failure, as previously reported by Medscape Medical News.
To find out more, Mr. Wong and colleagues analyzed 2,828 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study. They compared the stroke risk between 874 people with diabetic retinopathy and another 1,954 diabetics without this complication. The average age was 62 years and 62% were men.
Diabetic neuropathy at baseline was diagnosed using the Early Treatment Diabetic Retinopathy Study Severity Scale using seven-field stereoscopic fundus photographs.
A total of 117 participants experienced a stroke during a mean follow-up of 5.4 years.
The investigators found that diabetic retinopathy was more common among patients who had a stroke (41%) versus 31% of those without a stroke (P = .016). The link between diabetic retinopathy and stroke remained in an analysis adjusted for multiple factors, including baseline age, gender, race, total cholesterol, A1c, smoking, and more. Risk remained elevated, with a hazard ratio of 1.60 (95% confidence interval, 1.10-2.32; P = .015).
Regarding the potential for modifying this risk, the association was unaffected among participants randomly assigned to the ACCORD glucose intervention (P = .305), lipid intervention (P = .546), or blood pressure intervention (P = .422).
The study was a secondary analysis, so information on stroke type and location were unavailable.
The big picture
“Diabetic retinopathy is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to diabetic retinopathy has larger cardiovascular implications,” the researchers noted.
Despite these findings, the researchers suggest that patients with diabetic retinopathy receive aggressive medical management to try to reduce their stroke risk.
“It’s important for everyone with diabetes to maintain good blood glucose control, and those with established diabetic retinopathy should pay particular attention to meeting all the stroke prevention guidelines that are established by the American Stroke Association,” said Mr. Wong.
“Patients with established diabetic retinopathy should pay particular attention to meeting all stroke prevention guidelines established by the [American Heart Association],” he added.
Mr. Wong and colleagues would like to expand on these findings. Pending grant application and funding support, they propose conducting a prospective, observational trial in stroke patients with baseline diabetic retinopathy. One aim would be to identify the most common mechanisms leading to stroke in this population, “which would have important implications for prevention efforts,” he said.
Consistent Findings
“The results of the study showing that having diabetic retinopathy is also associated with an increase in stroke really isn’t surprising. There have been other studies, population-based studies, done in the past, that have found a similar relationship,” Larry B. Goldstein, MD, said in a video commentary on the findings.
“The results are actually quite consistent with several other studies that have evaluated the same relationship,” added Dr. Goldstein, who is chair of the department of neurology and codirector of the Kentucky Neuroscience Institute, University of Kentucky HealthCare, Lexington.
Mr. Wong and Dr. Goldstein have disclosed no relevant financial relationships. The NIH’s National Institute of Neurological Disorders and Stroke funded the study.
This article first appeared on Medscape.com.
REPORTING FROM ISC 2020
After gestational diabetes, longer lactation tied to lower risk for type 2
Among women with a history of gestational diabetes, a longer period of breastfeeding was associated with a lower probability of going on to develop type 2 diabetes, as well as a more favorable glucose metabolic biomarker profile. Women who breastfed for 2 years or longer had a 27% lower risk than that of those who did not breastfeed at all, even after adjustment for age, ethnicity, family history of diabetes, parity, age at first birth, smoking, diet quality, physical activity, and prepregnancy body mass index, according to findings published in Diabetes Care.
It remains to be seen if the association is causal, and if so, what mechanisms might connect breastfeeding duration to risk for type 2 diabetes, wrote study leaders Sylvia Ley, PhD, of Tulane University School of Public Health and Tropical Medicine, New Orleans, and the Harvard T.H. Chan School of Public Health, Boston, and Cuilin Zhang, MD, PhD, of the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md., and colleagues.
“It’s really nice to see this consistency and the long-term association being borne out in a very large sample of women with gestational diabetes,” Erica P. Gunderson, PhD, said in an interview about the study. Dr. Gunderson has conducted similar studies of her own, including one published in 2018 that showed an independent association between lactation and reduced diabetes risk in women (JAMA Intern Med. 2018;178:328-37). That analysis showed no sign that the presence of gestational diabetes affected the reduction of diabetes risk associated with lactation.
Dr. Gunderson noted that pregnancy is a hyperlipidemic state, with triglyceride levels sometimes doubling, likely in response to the need to support the placenta and the growing fetus. Lactation may help restore lipid levels to the prepregnancy state by redirecting lipids to breast milk. She and others are working to produce more direct evidence of metabolic changes in the postpartum period associated with lactation. “That’s where we don’t have much mechanistic evidence right now,” said Dr. Gunderson, a senior research scientist and epidemiologist at Kaiser Permanente Northern California, Oakland.
Gestational diabetes occurs in an estimated 5%-9% of pregnancies in the United States, and women who experience this complication are at greater risk of developing type 2 diabetes in the future. Findings from other studies have shown that longer lactation periods are associated with lowered risk of future type 2 disease (JAMA. 2005;294:2601-10).
In the latest study, the researchers included 4,372 women with a history of gestational diabetes, identified through the Nurses’ Health Study II. Participants were excluded if they had a history of cancer, cardiovascular disease, or multiple-birth pregnancy before the pregnancy during which they were diagnosed with gestational diabetes. In all, 873 women developed type 2 diabetes over 87,411 person-years of follow-up. The median age at gestational diabetes diagnosis was 31.8 years, and 49.8 years for diagnoses of type 2 diabetes.
After adjustment, the researchers found a steadying decline of risk for type 2 diabetes with increasing length of lactation: for up to 6 months of lactation, the hazard ratio was 1.05 (95% confidence interval, 0.82-1.34); for 6-12 months, the HR was 0.91 (95% CI, 0.71-1.15); 12-24 months, 0.84 (95% CI, 0.67-1.06); more than 24 months, 0.73 (95% CI, 0.57-0.93; P for trend = .004). Age, parity, primipara, prepregnancy body mass index, and age had no statistically significant effect modification on the association.
At a follow-up blood collection taken at median age of 58.2 years and 26.3 years after the gestational-diabetes index pregnancy, the researchers found associations between longer breastfeeding (greater than 24 months vs. 0 months) and lower hemoglobin A1c percentage (5.58 vs. 5.68; P for trend = .04), lower insulin levels (53.1 vs. 64.7 pmol/L; P for trend = .02), and lower C-peptide levels (3.42 vs. 3.88 ng/mL; P for trend = .02).
The study was supported by the National Institutes of Health. Dr. Ley was supported by a National Institute of General Medical Sciences grant from the NIH. None of the study authors reported any conflicts of interest, and neither did Dr. Gunderson.
SOURCE: Ley S et al. Diabetes Care. 2020 Feb 10. doi: 10.2337/dc19-2237.
Among women with a history of gestational diabetes, a longer period of breastfeeding was associated with a lower probability of going on to develop type 2 diabetes, as well as a more favorable glucose metabolic biomarker profile. Women who breastfed for 2 years or longer had a 27% lower risk than that of those who did not breastfeed at all, even after adjustment for age, ethnicity, family history of diabetes, parity, age at first birth, smoking, diet quality, physical activity, and prepregnancy body mass index, according to findings published in Diabetes Care.
It remains to be seen if the association is causal, and if so, what mechanisms might connect breastfeeding duration to risk for type 2 diabetes, wrote study leaders Sylvia Ley, PhD, of Tulane University School of Public Health and Tropical Medicine, New Orleans, and the Harvard T.H. Chan School of Public Health, Boston, and Cuilin Zhang, MD, PhD, of the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md., and colleagues.
“It’s really nice to see this consistency and the long-term association being borne out in a very large sample of women with gestational diabetes,” Erica P. Gunderson, PhD, said in an interview about the study. Dr. Gunderson has conducted similar studies of her own, including one published in 2018 that showed an independent association between lactation and reduced diabetes risk in women (JAMA Intern Med. 2018;178:328-37). That analysis showed no sign that the presence of gestational diabetes affected the reduction of diabetes risk associated with lactation.
Dr. Gunderson noted that pregnancy is a hyperlipidemic state, with triglyceride levels sometimes doubling, likely in response to the need to support the placenta and the growing fetus. Lactation may help restore lipid levels to the prepregnancy state by redirecting lipids to breast milk. She and others are working to produce more direct evidence of metabolic changes in the postpartum period associated with lactation. “That’s where we don’t have much mechanistic evidence right now,” said Dr. Gunderson, a senior research scientist and epidemiologist at Kaiser Permanente Northern California, Oakland.
Gestational diabetes occurs in an estimated 5%-9% of pregnancies in the United States, and women who experience this complication are at greater risk of developing type 2 diabetes in the future. Findings from other studies have shown that longer lactation periods are associated with lowered risk of future type 2 disease (JAMA. 2005;294:2601-10).
In the latest study, the researchers included 4,372 women with a history of gestational diabetes, identified through the Nurses’ Health Study II. Participants were excluded if they had a history of cancer, cardiovascular disease, or multiple-birth pregnancy before the pregnancy during which they were diagnosed with gestational diabetes. In all, 873 women developed type 2 diabetes over 87,411 person-years of follow-up. The median age at gestational diabetes diagnosis was 31.8 years, and 49.8 years for diagnoses of type 2 diabetes.
After adjustment, the researchers found a steadying decline of risk for type 2 diabetes with increasing length of lactation: for up to 6 months of lactation, the hazard ratio was 1.05 (95% confidence interval, 0.82-1.34); for 6-12 months, the HR was 0.91 (95% CI, 0.71-1.15); 12-24 months, 0.84 (95% CI, 0.67-1.06); more than 24 months, 0.73 (95% CI, 0.57-0.93; P for trend = .004). Age, parity, primipara, prepregnancy body mass index, and age had no statistically significant effect modification on the association.
At a follow-up blood collection taken at median age of 58.2 years and 26.3 years after the gestational-diabetes index pregnancy, the researchers found associations between longer breastfeeding (greater than 24 months vs. 0 months) and lower hemoglobin A1c percentage (5.58 vs. 5.68; P for trend = .04), lower insulin levels (53.1 vs. 64.7 pmol/L; P for trend = .02), and lower C-peptide levels (3.42 vs. 3.88 ng/mL; P for trend = .02).
The study was supported by the National Institutes of Health. Dr. Ley was supported by a National Institute of General Medical Sciences grant from the NIH. None of the study authors reported any conflicts of interest, and neither did Dr. Gunderson.
SOURCE: Ley S et al. Diabetes Care. 2020 Feb 10. doi: 10.2337/dc19-2237.
Among women with a history of gestational diabetes, a longer period of breastfeeding was associated with a lower probability of going on to develop type 2 diabetes, as well as a more favorable glucose metabolic biomarker profile. Women who breastfed for 2 years or longer had a 27% lower risk than that of those who did not breastfeed at all, even after adjustment for age, ethnicity, family history of diabetes, parity, age at first birth, smoking, diet quality, physical activity, and prepregnancy body mass index, according to findings published in Diabetes Care.
It remains to be seen if the association is causal, and if so, what mechanisms might connect breastfeeding duration to risk for type 2 diabetes, wrote study leaders Sylvia Ley, PhD, of Tulane University School of Public Health and Tropical Medicine, New Orleans, and the Harvard T.H. Chan School of Public Health, Boston, and Cuilin Zhang, MD, PhD, of the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md., and colleagues.
“It’s really nice to see this consistency and the long-term association being borne out in a very large sample of women with gestational diabetes,” Erica P. Gunderson, PhD, said in an interview about the study. Dr. Gunderson has conducted similar studies of her own, including one published in 2018 that showed an independent association between lactation and reduced diabetes risk in women (JAMA Intern Med. 2018;178:328-37). That analysis showed no sign that the presence of gestational diabetes affected the reduction of diabetes risk associated with lactation.
Dr. Gunderson noted that pregnancy is a hyperlipidemic state, with triglyceride levels sometimes doubling, likely in response to the need to support the placenta and the growing fetus. Lactation may help restore lipid levels to the prepregnancy state by redirecting lipids to breast milk. She and others are working to produce more direct evidence of metabolic changes in the postpartum period associated with lactation. “That’s where we don’t have much mechanistic evidence right now,” said Dr. Gunderson, a senior research scientist and epidemiologist at Kaiser Permanente Northern California, Oakland.
Gestational diabetes occurs in an estimated 5%-9% of pregnancies in the United States, and women who experience this complication are at greater risk of developing type 2 diabetes in the future. Findings from other studies have shown that longer lactation periods are associated with lowered risk of future type 2 disease (JAMA. 2005;294:2601-10).
In the latest study, the researchers included 4,372 women with a history of gestational diabetes, identified through the Nurses’ Health Study II. Participants were excluded if they had a history of cancer, cardiovascular disease, or multiple-birth pregnancy before the pregnancy during which they were diagnosed with gestational diabetes. In all, 873 women developed type 2 diabetes over 87,411 person-years of follow-up. The median age at gestational diabetes diagnosis was 31.8 years, and 49.8 years for diagnoses of type 2 diabetes.
After adjustment, the researchers found a steadying decline of risk for type 2 diabetes with increasing length of lactation: for up to 6 months of lactation, the hazard ratio was 1.05 (95% confidence interval, 0.82-1.34); for 6-12 months, the HR was 0.91 (95% CI, 0.71-1.15); 12-24 months, 0.84 (95% CI, 0.67-1.06); more than 24 months, 0.73 (95% CI, 0.57-0.93; P for trend = .004). Age, parity, primipara, prepregnancy body mass index, and age had no statistically significant effect modification on the association.
At a follow-up blood collection taken at median age of 58.2 years and 26.3 years after the gestational-diabetes index pregnancy, the researchers found associations between longer breastfeeding (greater than 24 months vs. 0 months) and lower hemoglobin A1c percentage (5.58 vs. 5.68; P for trend = .04), lower insulin levels (53.1 vs. 64.7 pmol/L; P for trend = .02), and lower C-peptide levels (3.42 vs. 3.88 ng/mL; P for trend = .02).
The study was supported by the National Institutes of Health. Dr. Ley was supported by a National Institute of General Medical Sciences grant from the NIH. None of the study authors reported any conflicts of interest, and neither did Dr. Gunderson.
SOURCE: Ley S et al. Diabetes Care. 2020 Feb 10. doi: 10.2337/dc19-2237.
FROM DIABETES CARE
Sharpest spikes in pediatric diabetes seen in Asian, Pacific Islander youth
according to a review of almost 70,000 children in the SEARCH for Diabetes in Youth Study, an ongoing, population-based surveillance project of individuals younger than 20 years.
“For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites,” wrote the investigators, led by Jasmin Divers, PhD, of the division of health services research, department of foundations of medicine, at New York University. “These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.”
SEARCH identified 14,638 cases of pediatric type 1 diabetes and 3,916 cases of type 2 diabetes from 2002 to 2015. The study draws participants from all 64 counties in Colorado, plus selected Indian reservations in Arizona and New Mexico under the direction of Colorado; all 46 counties in South Carolina; 8 in Ohio; 5 in Washington; and Kaiser Permanente Southern California health plan enrollees in 7 counties.
The investigators found steeper increases in age- and sex-adjusted incidence of type 1 diabetes from 2002 to 2015 among black youth (2.7% per year), Hispanic youth (4%), and Asian and Pacific Islander youth (4.4%), than among their white counterparts (0.7%). Incidence among Asians and Pacific Islanders did not change significantly during 2002-2010, but increased steeply during 2011-2015 (8.5% per year) for unknown reasons.
“In parallel with increased obesity prevalence in U.S. youths, the incidence of type 2 diabetes among adolescents has increased at a higher rate than that of type 1 diabetes, especially among racial-/ethnic-minority youths,” the authors noted.
The number of new cases of type 2 diagnosed in children younger than 10 years were too few to report on (181 total cases during 2002-2015), so the incidence analysis was limited to children who were aged 10-19 years at diagnosis. The steepest annual percentage changes were among Asians and Pacific Islander youth (7.7% per year), followed by Hispanic (6.5%), black (6.0%), and American Indian (3.7%) youth.
“Although the SEARCH population is similar demographically to the U.S. youth population, it is not designed to be nationally representative,” which is one of the limitations of the study, the investigators wrote.
The authors reported having no conflicts of interest.
SOURCE: Divers J et al. MMWR Morb Mortal Wkly Rep. 2020;69:161-5.
according to a review of almost 70,000 children in the SEARCH for Diabetes in Youth Study, an ongoing, population-based surveillance project of individuals younger than 20 years.
“For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites,” wrote the investigators, led by Jasmin Divers, PhD, of the division of health services research, department of foundations of medicine, at New York University. “These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.”
SEARCH identified 14,638 cases of pediatric type 1 diabetes and 3,916 cases of type 2 diabetes from 2002 to 2015. The study draws participants from all 64 counties in Colorado, plus selected Indian reservations in Arizona and New Mexico under the direction of Colorado; all 46 counties in South Carolina; 8 in Ohio; 5 in Washington; and Kaiser Permanente Southern California health plan enrollees in 7 counties.
The investigators found steeper increases in age- and sex-adjusted incidence of type 1 diabetes from 2002 to 2015 among black youth (2.7% per year), Hispanic youth (4%), and Asian and Pacific Islander youth (4.4%), than among their white counterparts (0.7%). Incidence among Asians and Pacific Islanders did not change significantly during 2002-2010, but increased steeply during 2011-2015 (8.5% per year) for unknown reasons.
“In parallel with increased obesity prevalence in U.S. youths, the incidence of type 2 diabetes among adolescents has increased at a higher rate than that of type 1 diabetes, especially among racial-/ethnic-minority youths,” the authors noted.
The number of new cases of type 2 diagnosed in children younger than 10 years were too few to report on (181 total cases during 2002-2015), so the incidence analysis was limited to children who were aged 10-19 years at diagnosis. The steepest annual percentage changes were among Asians and Pacific Islander youth (7.7% per year), followed by Hispanic (6.5%), black (6.0%), and American Indian (3.7%) youth.
“Although the SEARCH population is similar demographically to the U.S. youth population, it is not designed to be nationally representative,” which is one of the limitations of the study, the investigators wrote.
The authors reported having no conflicts of interest.
SOURCE: Divers J et al. MMWR Morb Mortal Wkly Rep. 2020;69:161-5.
according to a review of almost 70,000 children in the SEARCH for Diabetes in Youth Study, an ongoing, population-based surveillance project of individuals younger than 20 years.
“For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites,” wrote the investigators, led by Jasmin Divers, PhD, of the division of health services research, department of foundations of medicine, at New York University. “These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.”
SEARCH identified 14,638 cases of pediatric type 1 diabetes and 3,916 cases of type 2 diabetes from 2002 to 2015. The study draws participants from all 64 counties in Colorado, plus selected Indian reservations in Arizona and New Mexico under the direction of Colorado; all 46 counties in South Carolina; 8 in Ohio; 5 in Washington; and Kaiser Permanente Southern California health plan enrollees in 7 counties.
The investigators found steeper increases in age- and sex-adjusted incidence of type 1 diabetes from 2002 to 2015 among black youth (2.7% per year), Hispanic youth (4%), and Asian and Pacific Islander youth (4.4%), than among their white counterparts (0.7%). Incidence among Asians and Pacific Islanders did not change significantly during 2002-2010, but increased steeply during 2011-2015 (8.5% per year) for unknown reasons.
“In parallel with increased obesity prevalence in U.S. youths, the incidence of type 2 diabetes among adolescents has increased at a higher rate than that of type 1 diabetes, especially among racial-/ethnic-minority youths,” the authors noted.
The number of new cases of type 2 diagnosed in children younger than 10 years were too few to report on (181 total cases during 2002-2015), so the incidence analysis was limited to children who were aged 10-19 years at diagnosis. The steepest annual percentage changes were among Asians and Pacific Islander youth (7.7% per year), followed by Hispanic (6.5%), black (6.0%), and American Indian (3.7%) youth.
“Although the SEARCH population is similar demographically to the U.S. youth population, it is not designed to be nationally representative,” which is one of the limitations of the study, the investigators wrote.
The authors reported having no conflicts of interest.
SOURCE: Divers J et al. MMWR Morb Mortal Wkly Rep. 2020;69:161-5.
FROM THE MORBIDITY AND MORTALITY WEEKLY REPORT
Tools for preventing heart failure
SNOWMASS, COLO. – If ever there was a major chronic disease that’s teed up and ready to be stamped into submission through diligent application of preventive medicine, it’s the epidemic of heart failure.
“The best way to treat heart failure is to prevent it in the first place. There will be more than 1 million new cases of heart failure this year, and the vast majority of them could have been prevented,” Gregg C. Fonarow, MD, asserted at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Using firmly evidence-based, guideline-directed therapies, it’s often possible to prevent patients at high risk for developing heart failure (HF) from actually doing so. Or, in the terminology of the ACC/American Heart Association heart failure guidelines coauthored by Dr. Fonarow, the goal is to keep patients who are stage A – that is, pre-HF but at high risk because of hypertension, coronary artery disease, diabetes, family history of cardiomyopathy, or other reasons – from progressing to stage B, marked by asymptomatic left ventricular dysfunction, a prior MI, or asymptomatic valvular disease; and blocking those who are stage B from then moving on to stage C, the classic symptomatic form of HF; and thence to end-stage stage D disease.
Heart failure is an enormous public health problem, and one of the most expensive of all diseases. The prognostic impact of newly diagnosed HF is profound, with 10-15 years of life lost, compared with the general population. Even today, roughly one in five newly diagnosed patients won’t survive for a year, and the 5-year mortality is about 50%, said Dr. Fonarow, who is professor of cardiovascular medicine and chief of the division of cardiology at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center, also in Los Angeles.
Symptomatic stage C is “the tip of the iceberg,” the cardiologist stressed. Vastly more patients are in stages A and B. In order to keep them from progressing to stage C, it’s first necessary to identify them. That’s why the 2013 guidelines give a class IC recommendation for periodic evaluation for signs and symptoms of HF in patients who are at high risk, and for a noninvasive assessment of left ventricular ejection fraction in those with a strong family history of cardiomyopathy or who are on cardiotoxic drugs (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-239).
The two biggest risk factors for the development of symptomatic stage C HF are hypertension and atherosclerotic cardiovascular disease. Close to 80% of patients presenting with heart failure have prevalent hypertension, and a history of ischemic heart disease is nearly as common.
Other major modifiable risk factors are diabetes, overweight and obesity, metabolic syndrome, dyslipidemia, smoking, valvular heart disease, and chronic kidney disease.
Hypertension
Most patients with high blood pressure believe they’re on antihypertensive medication to prevent MI and stroke, but in reality the largest benefit is what Dr. Fonarow termed the “phenomenal” reduction in the risk of developing HF, which amounted to a 52% relative risk reduction in one meta-analysis of older randomized trials. In the contemporary era, the landmark SPRINT trial of close to 10,000 randomized hypertensive patients showed that more-intensive blood pressure lowering to a target systolic BP of less than 120 mm Hg resulted in a 38% reduction in the risk of new-onset HF, compared with standard treatment to a target of less than 140 mm Hg. That’s why the 2017 focused update of the HF guidelines gives a strong class IB recommendation for a target blood pressure of less than 130/80 mm Hg in hypertensive patients with stage A HF (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803).
Atherosclerotic cardiovascular disease
Within 6 years after diagnosis of an MI, 22% of men and 46% of women will develop symptomatic heart failure. Intensive statin therapy gets a strong recommendation post MI in the guidelines, not only because in a meta-analysis of four major randomized trials it resulted in a further 64% reduction in the risk of coronary death or recurrent MI, compared with moderate statin therapy, but also because of the 27% relative risk reduction in new-onset HF. ACE inhibitors get a class IA recommendation for prevention of symptomatic HF in patients who are stage A with a history of atherosclerotic disease, diabetes, or hypertension. Angiotensin receptor blockers get a class IC recommendation.
Diabetes
Diabetes markedly increases the risk of developing HF: by two to four times overall and by four to eight times in younger diabetes patients. The two chronic diseases are highly comorbid, with roughly 45% of patients with HF also having diabetes. Moreover, diabetes in HF patients is associated with a substantially worse prognosis, even when standard HF therapies are applied.
Choices regarding glycemic management can markedly affect HF risk and outcomes. Randomized trials show that the peroxisome proliferator-activated receptor agonists double the risk of HF. The glucagonlike peptide–1 receptor agonists are absolutely neutral with regard to HF outcomes. Similarly, the dipeptidyl peptidase–4 inhibitors have no impact on the risks of major adverse cardiovascular events or HF. Intensive glycemic control has no impact on the risk of new-onset HF. Insulin therapy, too, is neutral on this score.
“Depressingly, even lifestyle modification with weight loss, once you have type 2 diabetes, does not lower the risk,” Dr. Fonarow continued.
In contrast, the sodium-glucose transporter 2 (SGLT2) inhibitors have impressive cardiovascular and renal protective benefits in patients with type 2 diabetes, as demonstrated in a meta-analysis of more than 34,000 participants in the randomized trials of empagliflozin (Jardiance) in EMPA-REG OUTCOME, canagliflozin (Invokana) in CANVAS/CANVAS-R, and dapagliflozin (Farxiga) in DECLARE-TIMI 58. The SGLT2 inhibitors collectively reduced the risk of HF hospitalization by 21% in participants with no baseline history of the disease and by 29% in those with a history of HF. Moreover, the risk of progression of renal disease was reduced by 45% (Lancet. 2019 Jan 5;393[10166]:31-9).
More recently, the landmark DAPA-HF trial established SGLT2 inhibitor therapy as part of standard-of-care, guideline-directed medical therapy for patients with HF with reduced ejection fraction regardless of whether they have comorbid type 2 diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).
These are remarkable medications, generally very well tolerated, and it’s critical that cardiologists get on board in prescribing them, Dr. Fonarow emphasized. He alerted his colleagues to what he called an “incredibly helpful” review article that provides practical guidance for cardiologists in how to start using the SGLT2 inhibitors (JACC Heart Fail. 2019 Feb;7[2]:169-72).
“It’s pretty straightforward,” according to Dr. Fonarow. “If you’re comfortable enough in using ACE inhibitors, angiotensin receptor blockers, and beta-blockers, I think you’ll find these medications fit similarly when you actually get experience in utilizing them.”
He reported serving as a consultant to 10 pharmaceutical or medical device companies.
SNOWMASS, COLO. – If ever there was a major chronic disease that’s teed up and ready to be stamped into submission through diligent application of preventive medicine, it’s the epidemic of heart failure.
“The best way to treat heart failure is to prevent it in the first place. There will be more than 1 million new cases of heart failure this year, and the vast majority of them could have been prevented,” Gregg C. Fonarow, MD, asserted at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Using firmly evidence-based, guideline-directed therapies, it’s often possible to prevent patients at high risk for developing heart failure (HF) from actually doing so. Or, in the terminology of the ACC/American Heart Association heart failure guidelines coauthored by Dr. Fonarow, the goal is to keep patients who are stage A – that is, pre-HF but at high risk because of hypertension, coronary artery disease, diabetes, family history of cardiomyopathy, or other reasons – from progressing to stage B, marked by asymptomatic left ventricular dysfunction, a prior MI, or asymptomatic valvular disease; and blocking those who are stage B from then moving on to stage C, the classic symptomatic form of HF; and thence to end-stage stage D disease.
Heart failure is an enormous public health problem, and one of the most expensive of all diseases. The prognostic impact of newly diagnosed HF is profound, with 10-15 years of life lost, compared with the general population. Even today, roughly one in five newly diagnosed patients won’t survive for a year, and the 5-year mortality is about 50%, said Dr. Fonarow, who is professor of cardiovascular medicine and chief of the division of cardiology at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center, also in Los Angeles.
Symptomatic stage C is “the tip of the iceberg,” the cardiologist stressed. Vastly more patients are in stages A and B. In order to keep them from progressing to stage C, it’s first necessary to identify them. That’s why the 2013 guidelines give a class IC recommendation for periodic evaluation for signs and symptoms of HF in patients who are at high risk, and for a noninvasive assessment of left ventricular ejection fraction in those with a strong family history of cardiomyopathy or who are on cardiotoxic drugs (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-239).
The two biggest risk factors for the development of symptomatic stage C HF are hypertension and atherosclerotic cardiovascular disease. Close to 80% of patients presenting with heart failure have prevalent hypertension, and a history of ischemic heart disease is nearly as common.
Other major modifiable risk factors are diabetes, overweight and obesity, metabolic syndrome, dyslipidemia, smoking, valvular heart disease, and chronic kidney disease.
Hypertension
Most patients with high blood pressure believe they’re on antihypertensive medication to prevent MI and stroke, but in reality the largest benefit is what Dr. Fonarow termed the “phenomenal” reduction in the risk of developing HF, which amounted to a 52% relative risk reduction in one meta-analysis of older randomized trials. In the contemporary era, the landmark SPRINT trial of close to 10,000 randomized hypertensive patients showed that more-intensive blood pressure lowering to a target systolic BP of less than 120 mm Hg resulted in a 38% reduction in the risk of new-onset HF, compared with standard treatment to a target of less than 140 mm Hg. That’s why the 2017 focused update of the HF guidelines gives a strong class IB recommendation for a target blood pressure of less than 130/80 mm Hg in hypertensive patients with stage A HF (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803).
Atherosclerotic cardiovascular disease
Within 6 years after diagnosis of an MI, 22% of men and 46% of women will develop symptomatic heart failure. Intensive statin therapy gets a strong recommendation post MI in the guidelines, not only because in a meta-analysis of four major randomized trials it resulted in a further 64% reduction in the risk of coronary death or recurrent MI, compared with moderate statin therapy, but also because of the 27% relative risk reduction in new-onset HF. ACE inhibitors get a class IA recommendation for prevention of symptomatic HF in patients who are stage A with a history of atherosclerotic disease, diabetes, or hypertension. Angiotensin receptor blockers get a class IC recommendation.
Diabetes
Diabetes markedly increases the risk of developing HF: by two to four times overall and by four to eight times in younger diabetes patients. The two chronic diseases are highly comorbid, with roughly 45% of patients with HF also having diabetes. Moreover, diabetes in HF patients is associated with a substantially worse prognosis, even when standard HF therapies are applied.
Choices regarding glycemic management can markedly affect HF risk and outcomes. Randomized trials show that the peroxisome proliferator-activated receptor agonists double the risk of HF. The glucagonlike peptide–1 receptor agonists are absolutely neutral with regard to HF outcomes. Similarly, the dipeptidyl peptidase–4 inhibitors have no impact on the risks of major adverse cardiovascular events or HF. Intensive glycemic control has no impact on the risk of new-onset HF. Insulin therapy, too, is neutral on this score.
“Depressingly, even lifestyle modification with weight loss, once you have type 2 diabetes, does not lower the risk,” Dr. Fonarow continued.
In contrast, the sodium-glucose transporter 2 (SGLT2) inhibitors have impressive cardiovascular and renal protective benefits in patients with type 2 diabetes, as demonstrated in a meta-analysis of more than 34,000 participants in the randomized trials of empagliflozin (Jardiance) in EMPA-REG OUTCOME, canagliflozin (Invokana) in CANVAS/CANVAS-R, and dapagliflozin (Farxiga) in DECLARE-TIMI 58. The SGLT2 inhibitors collectively reduced the risk of HF hospitalization by 21% in participants with no baseline history of the disease and by 29% in those with a history of HF. Moreover, the risk of progression of renal disease was reduced by 45% (Lancet. 2019 Jan 5;393[10166]:31-9).
More recently, the landmark DAPA-HF trial established SGLT2 inhibitor therapy as part of standard-of-care, guideline-directed medical therapy for patients with HF with reduced ejection fraction regardless of whether they have comorbid type 2 diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).
These are remarkable medications, generally very well tolerated, and it’s critical that cardiologists get on board in prescribing them, Dr. Fonarow emphasized. He alerted his colleagues to what he called an “incredibly helpful” review article that provides practical guidance for cardiologists in how to start using the SGLT2 inhibitors (JACC Heart Fail. 2019 Feb;7[2]:169-72).
“It’s pretty straightforward,” according to Dr. Fonarow. “If you’re comfortable enough in using ACE inhibitors, angiotensin receptor blockers, and beta-blockers, I think you’ll find these medications fit similarly when you actually get experience in utilizing them.”
He reported serving as a consultant to 10 pharmaceutical or medical device companies.
SNOWMASS, COLO. – If ever there was a major chronic disease that’s teed up and ready to be stamped into submission through diligent application of preventive medicine, it’s the epidemic of heart failure.
“The best way to treat heart failure is to prevent it in the first place. There will be more than 1 million new cases of heart failure this year, and the vast majority of them could have been prevented,” Gregg C. Fonarow, MD, asserted at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Using firmly evidence-based, guideline-directed therapies, it’s often possible to prevent patients at high risk for developing heart failure (HF) from actually doing so. Or, in the terminology of the ACC/American Heart Association heart failure guidelines coauthored by Dr. Fonarow, the goal is to keep patients who are stage A – that is, pre-HF but at high risk because of hypertension, coronary artery disease, diabetes, family history of cardiomyopathy, or other reasons – from progressing to stage B, marked by asymptomatic left ventricular dysfunction, a prior MI, or asymptomatic valvular disease; and blocking those who are stage B from then moving on to stage C, the classic symptomatic form of HF; and thence to end-stage stage D disease.
Heart failure is an enormous public health problem, and one of the most expensive of all diseases. The prognostic impact of newly diagnosed HF is profound, with 10-15 years of life lost, compared with the general population. Even today, roughly one in five newly diagnosed patients won’t survive for a year, and the 5-year mortality is about 50%, said Dr. Fonarow, who is professor of cardiovascular medicine and chief of the division of cardiology at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center, also in Los Angeles.
Symptomatic stage C is “the tip of the iceberg,” the cardiologist stressed. Vastly more patients are in stages A and B. In order to keep them from progressing to stage C, it’s first necessary to identify them. That’s why the 2013 guidelines give a class IC recommendation for periodic evaluation for signs and symptoms of HF in patients who are at high risk, and for a noninvasive assessment of left ventricular ejection fraction in those with a strong family history of cardiomyopathy or who are on cardiotoxic drugs (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-239).
The two biggest risk factors for the development of symptomatic stage C HF are hypertension and atherosclerotic cardiovascular disease. Close to 80% of patients presenting with heart failure have prevalent hypertension, and a history of ischemic heart disease is nearly as common.
Other major modifiable risk factors are diabetes, overweight and obesity, metabolic syndrome, dyslipidemia, smoking, valvular heart disease, and chronic kidney disease.
Hypertension
Most patients with high blood pressure believe they’re on antihypertensive medication to prevent MI and stroke, but in reality the largest benefit is what Dr. Fonarow termed the “phenomenal” reduction in the risk of developing HF, which amounted to a 52% relative risk reduction in one meta-analysis of older randomized trials. In the contemporary era, the landmark SPRINT trial of close to 10,000 randomized hypertensive patients showed that more-intensive blood pressure lowering to a target systolic BP of less than 120 mm Hg resulted in a 38% reduction in the risk of new-onset HF, compared with standard treatment to a target of less than 140 mm Hg. That’s why the 2017 focused update of the HF guidelines gives a strong class IB recommendation for a target blood pressure of less than 130/80 mm Hg in hypertensive patients with stage A HF (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803).
Atherosclerotic cardiovascular disease
Within 6 years after diagnosis of an MI, 22% of men and 46% of women will develop symptomatic heart failure. Intensive statin therapy gets a strong recommendation post MI in the guidelines, not only because in a meta-analysis of four major randomized trials it resulted in a further 64% reduction in the risk of coronary death or recurrent MI, compared with moderate statin therapy, but also because of the 27% relative risk reduction in new-onset HF. ACE inhibitors get a class IA recommendation for prevention of symptomatic HF in patients who are stage A with a history of atherosclerotic disease, diabetes, or hypertension. Angiotensin receptor blockers get a class IC recommendation.
Diabetes
Diabetes markedly increases the risk of developing HF: by two to four times overall and by four to eight times in younger diabetes patients. The two chronic diseases are highly comorbid, with roughly 45% of patients with HF also having diabetes. Moreover, diabetes in HF patients is associated with a substantially worse prognosis, even when standard HF therapies are applied.
Choices regarding glycemic management can markedly affect HF risk and outcomes. Randomized trials show that the peroxisome proliferator-activated receptor agonists double the risk of HF. The glucagonlike peptide–1 receptor agonists are absolutely neutral with regard to HF outcomes. Similarly, the dipeptidyl peptidase–4 inhibitors have no impact on the risks of major adverse cardiovascular events or HF. Intensive glycemic control has no impact on the risk of new-onset HF. Insulin therapy, too, is neutral on this score.
“Depressingly, even lifestyle modification with weight loss, once you have type 2 diabetes, does not lower the risk,” Dr. Fonarow continued.
In contrast, the sodium-glucose transporter 2 (SGLT2) inhibitors have impressive cardiovascular and renal protective benefits in patients with type 2 diabetes, as demonstrated in a meta-analysis of more than 34,000 participants in the randomized trials of empagliflozin (Jardiance) in EMPA-REG OUTCOME, canagliflozin (Invokana) in CANVAS/CANVAS-R, and dapagliflozin (Farxiga) in DECLARE-TIMI 58. The SGLT2 inhibitors collectively reduced the risk of HF hospitalization by 21% in participants with no baseline history of the disease and by 29% in those with a history of HF. Moreover, the risk of progression of renal disease was reduced by 45% (Lancet. 2019 Jan 5;393[10166]:31-9).
More recently, the landmark DAPA-HF trial established SGLT2 inhibitor therapy as part of standard-of-care, guideline-directed medical therapy for patients with HF with reduced ejection fraction regardless of whether they have comorbid type 2 diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).
These are remarkable medications, generally very well tolerated, and it’s critical that cardiologists get on board in prescribing them, Dr. Fonarow emphasized. He alerted his colleagues to what he called an “incredibly helpful” review article that provides practical guidance for cardiologists in how to start using the SGLT2 inhibitors (JACC Heart Fail. 2019 Feb;7[2]:169-72).
“It’s pretty straightforward,” according to Dr. Fonarow. “If you’re comfortable enough in using ACE inhibitors, angiotensin receptor blockers, and beta-blockers, I think you’ll find these medications fit similarly when you actually get experience in utilizing them.”
He reported serving as a consultant to 10 pharmaceutical or medical device companies.
EXPERT ANALYSIS FROM ACC SNOWMASS 2020
FDA issues MiniMed600 insulin pump recall
according to a Food and Drug Administration MedWatch release.
A class I recall such as this indicates that there is reasonable probability that using a defective pump will cause serious adverse health consequences or death, the agency said in the recall notice. It said the company has received more than 26,000 complaints regarding this problem and is aware of 2,175 injuries and 1 death so far. In all, 322,005 devices have been recalled.
If the pumps in question – Model 630G (distributed September 2016 to October 2019) and 670G (June 2017 to August 2019) – have broken or missing retainer rings, the insulin cartridge can end up loose in the reservoir compartment, which can lead to incorrect dosing and therefore potentially to hyperglycemia or hypoglycemia, according to the statement.
Model 630G was approved by the FDA in August 2016, and the 670G in September that same year.
On Nov. 21, 2019, Medtronic advised patients with type 1 diabetes who use the pumps to:
- Examine the retainer ring to see if it is loose, broken, or missing.
- Stop using the pump if the reservoir does not lock correctly or if the retainer ring is loose, damaged, or missing. Patients should contact Medtronic for a replacement pump and follow their doctor’s recommendations and perform manual insulin injections.
- Continue using the pump if the reservoir locks in place correctly.
- Check pump and retainer ring if the pump is dropped by accident, and stop use if it is damaged.
- Check the pump and retainer ring every set change to verify the reservoir is locked correctly.
More information regarding this recall, including how to contact Medtronic Technical Support, can be found on the FDA website.
according to a Food and Drug Administration MedWatch release.
A class I recall such as this indicates that there is reasonable probability that using a defective pump will cause serious adverse health consequences or death, the agency said in the recall notice. It said the company has received more than 26,000 complaints regarding this problem and is aware of 2,175 injuries and 1 death so far. In all, 322,005 devices have been recalled.
If the pumps in question – Model 630G (distributed September 2016 to October 2019) and 670G (June 2017 to August 2019) – have broken or missing retainer rings, the insulin cartridge can end up loose in the reservoir compartment, which can lead to incorrect dosing and therefore potentially to hyperglycemia or hypoglycemia, according to the statement.
Model 630G was approved by the FDA in August 2016, and the 670G in September that same year.
On Nov. 21, 2019, Medtronic advised patients with type 1 diabetes who use the pumps to:
- Examine the retainer ring to see if it is loose, broken, or missing.
- Stop using the pump if the reservoir does not lock correctly or if the retainer ring is loose, damaged, or missing. Patients should contact Medtronic for a replacement pump and follow their doctor’s recommendations and perform manual insulin injections.
- Continue using the pump if the reservoir locks in place correctly.
- Check pump and retainer ring if the pump is dropped by accident, and stop use if it is damaged.
- Check the pump and retainer ring every set change to verify the reservoir is locked correctly.
More information regarding this recall, including how to contact Medtronic Technical Support, can be found on the FDA website.
according to a Food and Drug Administration MedWatch release.
A class I recall such as this indicates that there is reasonable probability that using a defective pump will cause serious adverse health consequences or death, the agency said in the recall notice. It said the company has received more than 26,000 complaints regarding this problem and is aware of 2,175 injuries and 1 death so far. In all, 322,005 devices have been recalled.
If the pumps in question – Model 630G (distributed September 2016 to October 2019) and 670G (June 2017 to August 2019) – have broken or missing retainer rings, the insulin cartridge can end up loose in the reservoir compartment, which can lead to incorrect dosing and therefore potentially to hyperglycemia or hypoglycemia, according to the statement.
Model 630G was approved by the FDA in August 2016, and the 670G in September that same year.
On Nov. 21, 2019, Medtronic advised patients with type 1 diabetes who use the pumps to:
- Examine the retainer ring to see if it is loose, broken, or missing.
- Stop using the pump if the reservoir does not lock correctly or if the retainer ring is loose, damaged, or missing. Patients should contact Medtronic for a replacement pump and follow their doctor’s recommendations and perform manual insulin injections.
- Continue using the pump if the reservoir locks in place correctly.
- Check pump and retainer ring if the pump is dropped by accident, and stop use if it is damaged.
- Check the pump and retainer ring every set change to verify the reservoir is locked correctly.
More information regarding this recall, including how to contact Medtronic Technical Support, can be found on the FDA website.
Cardiovascular disease risk higher in patients with schizophrenia, metabolic syndrome
Metabolic syndrome is common among patients with schizophrenia, and those with metabolic syndrome are at significantly higher risk for cardiovascular disease, according to Shadi Naderyan Fe’li of the department of biostatistics and epidemiology at Shahid Sadoughi University of Medical Sciences in Yazd, Iran, and associates.
The cross-sectional study, performed on 100 patients with schizophrenia (83 men, 17 women), was published in the Medical Journal of the Islamic Republic of Iran. (men, 21.7%; women, 52.9%); the most common component of metabolic disorder was low HDL cholesterol in males and abdominal adiposity in females.
Based on Framingham Risk Scores, 76% of study participants had a low risk of cardiovascular disease, 16% had intermediate risk, and 8% had high risk. However, patients were almost twice as likely to have intermediate or high risk of cardiovascular disease if they also had metabolic syndrome (P = .042).
“Considering the findings of this study as well as other recent reports, psychiatrists and health care staff should be informed about the potential metabolic side effects of antipsychotics and unhealthy lifestyles among these patients. Furthermore, regular monitoring of metabolic risk factors is suggested. In addition, medical and behavioral interventions should be conducted for patients with [metabolic syndrome],” the investigators concluded.
The investigators reported that they had no conflicts of interest.
SOURCE: Fe’li SN et al. Med J Islam Repub Iran. 2019 Sep 16. doi: 10.34171/mjiri.33.97.
Metabolic syndrome is common among patients with schizophrenia, and those with metabolic syndrome are at significantly higher risk for cardiovascular disease, according to Shadi Naderyan Fe’li of the department of biostatistics and epidemiology at Shahid Sadoughi University of Medical Sciences in Yazd, Iran, and associates.
The cross-sectional study, performed on 100 patients with schizophrenia (83 men, 17 women), was published in the Medical Journal of the Islamic Republic of Iran. (men, 21.7%; women, 52.9%); the most common component of metabolic disorder was low HDL cholesterol in males and abdominal adiposity in females.
Based on Framingham Risk Scores, 76% of study participants had a low risk of cardiovascular disease, 16% had intermediate risk, and 8% had high risk. However, patients were almost twice as likely to have intermediate or high risk of cardiovascular disease if they also had metabolic syndrome (P = .042).
“Considering the findings of this study as well as other recent reports, psychiatrists and health care staff should be informed about the potential metabolic side effects of antipsychotics and unhealthy lifestyles among these patients. Furthermore, regular monitoring of metabolic risk factors is suggested. In addition, medical and behavioral interventions should be conducted for patients with [metabolic syndrome],” the investigators concluded.
The investigators reported that they had no conflicts of interest.
SOURCE: Fe’li SN et al. Med J Islam Repub Iran. 2019 Sep 16. doi: 10.34171/mjiri.33.97.
Metabolic syndrome is common among patients with schizophrenia, and those with metabolic syndrome are at significantly higher risk for cardiovascular disease, according to Shadi Naderyan Fe’li of the department of biostatistics and epidemiology at Shahid Sadoughi University of Medical Sciences in Yazd, Iran, and associates.
The cross-sectional study, performed on 100 patients with schizophrenia (83 men, 17 women), was published in the Medical Journal of the Islamic Republic of Iran. (men, 21.7%; women, 52.9%); the most common component of metabolic disorder was low HDL cholesterol in males and abdominal adiposity in females.
Based on Framingham Risk Scores, 76% of study participants had a low risk of cardiovascular disease, 16% had intermediate risk, and 8% had high risk. However, patients were almost twice as likely to have intermediate or high risk of cardiovascular disease if they also had metabolic syndrome (P = .042).
“Considering the findings of this study as well as other recent reports, psychiatrists and health care staff should be informed about the potential metabolic side effects of antipsychotics and unhealthy lifestyles among these patients. Furthermore, regular monitoring of metabolic risk factors is suggested. In addition, medical and behavioral interventions should be conducted for patients with [metabolic syndrome],” the investigators concluded.
The investigators reported that they had no conflicts of interest.
SOURCE: Fe’li SN et al. Med J Islam Repub Iran. 2019 Sep 16. doi: 10.34171/mjiri.33.97.
FROM THE MEDICAL JOURNAL OF THE ISLAMIC REPUBLIC OF IRAN
Data emerging to support personalized nutrition in oncology
SAN DIEGO – When Dawn Lemanne, MD, MPH, meets with cancer patients and their families, the question invariably comes up: “What should I eat?”
“The answer always is, ‘It depends,’” Dr. Lemanne, an oncologist who founded Oregon Integrative Oncology in Ashland, said at Natural Supplements: An Evidence-Based Update, presented by Scripps Center for Integrative Medicine. “The answers are not the same for each of these patients.”
According to Dr. Lemanne, targeted nutrition is evolving as a key component of cancer care. One of the goals of this approach is to decrease mTOR signaling. Normally, mTOR signaling promotes cell proliferation and metabolism; aberrant mTOR signaling can contribute to cancer initiation and progression.
“When mTOR speaks it says, ‘grow,’” said Dr. Lemanne, who is also an assistant professor of clinical medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona in Tucson. This message is meant to be heard by normal tissues, to stimulate normal tissue proliferation, such as in growing children or when a wound needs to be healed.
“However, cancer cells can hear and respond to mTOR’s message,” she said. “Normal cells may listen to mTOR’s ‘grow’ message or not, depending on the task they perform. Once we reach adulthood, we all likely have some precancerous or cancerous cells around, but they’re usually dormant. That’s why once you’re an adult, however, you don’t want too much mTOR signaling, because that might stimulate growth of things you definitely don’t want to grow.”
Having excessive levels of the growth hormone insulin-like growth factor-1 (IGF-1) also appears to play a role in cancer risk. Researchers studying members of a South American clan with Laron dwarfism – an inherited IGF-1 deficiency – found that besides being very short, affected members of this family rarely develop cancer (Cells. 2019;8[6]:596). “They also don’t get diabetes,” Dr. Lemanne said. “What we see in those with Laron dwarfism is that mTOR signaling is missing.”
She went on to note that studying type 2 diabetes gives physicians “a clue as to what dietary measures we might offer our patients in terms of decreasing their risk of dying from cancer or getting cancer.” The most common types of cancer are indeed more common in patients with type 2 diabetes. In addition, once someone with type 2 diabetes is diagnosed with cancer, their prognosis is poorer, compared with a cancer patient without diabetes.
“Metformin is often prescribed to patients with type 2 diabetes because it helps keep blood sugar low,” she said. “What’s fascinating is that diabetics on metformin develop cancer less frequently than diabetics not taking this drug. And also interesting, those diabetics who do develop cancer seem to do better if they’re on metformin before and after diagnosis.”
On the other hand, exogenous insulin therapy given to people with type 2 diabetes doubles the risk of cancer. Consistent with this is the two-decades-old finding that an elevated fasting insulin level also is associated with a poor breast cancer prognosis (J Clin Oncol. 2002 Jan 1;20[1]:42-51). “It’s really important to understand that, in a person destined to become a type 2 diabetic, the level of fasting insulin rises long before fasting glucose becomes abnormally high,” Dr. Lemanne explained. “A normal fasting glucose doesn’t let you off the hook in terms of checking your patient for insulin resistance.
“We will miss diagnosing many patients with dangerous insulin resistance and prediabetes if we don’t check the fasting glucose and the fasting insulin levels together. If the fasting insulin level is high, it’s important to limit carbohydrate intake enough to bring it down permanently, even when the fasting glucose is normal, or the patient is likely at increased risk for developing cancer.”
Two large, prospective randomized trials have examined breast cancer and diet: the Women’s Intervention Study (WINS) and the Women’s Health Eating and Living Study (WHEL). Patients in both trials had early stage breast cancer and were put on low-fat diets. In the end, there was a weak to negligible connection between breast cancer survival and dietary fat restriction. “That kind of shook up the oncology world,” Dr. Lemanne said, “because before these two studies, everyone ‘knew’ that dietary fat was related to breast cancer risk. These studies showed that wasn’t the case at all.”
According to Dr. Lemanne, unexpectedly, moderate carbohydrate restriction has been associated with lower risk of breast cancer recurrence in patients with postmenopausal hormone-receptor expressing breast cancer. Researchers at the University of California, San Diego, conducted a subanalysis of 265 postmenopausal patients with estrogen receptor positive breast cancer from the WHEL cohort (Cancer Epidemiol Biomarkers Prev. 2014 23[7]:1273-9). The recurrence risk was halved in those who cut their carbohydrate intake after diagnosis. The amount of decrease was modest, only 27 grams per day – the equivalent of one banana. “That is on par with a lot of our drugs, and maybe a little bit better,” she said. The effect was strongest if the breast tumor expressed IGF-1 receptor. Dr. Lemanne pointed out that decreasing dietary carbohydrate load was not the only treatment. These patients also had appropriate conventional cancer treatments, including surgery, radiation, and chemotherapy. “If we cut just some of the daily carb load in these patients, they might have a better cancer prognosis,” she said.
Overweight or obese patients with colon cancer also may benefit from moderate carbohydrate restriction. The CALGB 89803 study assessed 1,011 subjects with stage III colon cancer. It found that the subjects in the highest quintile of daily glycemic load and total carbohydrate intake had an increased risk of cancer recurrence and mortality (hazard ratio, 2.26; J Nat Cancer Inst. 2012;104[22]:1702-11). “This is pretty strong evidence that glycemic load and total carbohydrate intake play a role in colon cancer recurrence, but there’s a caveat here,” she said. “The effect was seen only in patients who were overweight or obese.” There was no association between carbohydrate intake and colon cancer recurrence in the absence of overweight or obesity.
Based on existing evidence, she said,
“That’s pretty modest; that’s 400 calories of carbohydrates per day,” Dr. Lemanne said. “I tell patients that they can have fruit, starchy vegetables, and even very small amounts of healthy whole grains, although I’m not a fan of grains due to the heavy carbohydrate load. All those things are OK. We’re not talking about jelly beans and white sugar.
“I also have them measure their fasting glucose each day, because different people have different blood glucose responses to the same food.” The goals she aims for with many of her patients are a fasting morning glucose between 79 and 83 mg/dL consistently, an HbA1c of 5.4 or less, and a BMI of 24.9 kg/m2 or less. “This set of goals, however, has to be individualized,” she said.
The ketogenic diet is another form of carb restriction, “but it’s much more drastic,” Dr. Lemanne said. “Most people require a carbohydrate load below 30 grams a day to enter a state of ketosis. But ketosis lowers the blood sugar and dampens the mTOR signaling.”
Evidence is emerging to support the use of a ketogenic diet as an adjunct to radiation therapy and as part of a complete course of treatment for glioblastoma multiforme and cancer cachexia. As an adjunct to radiation, a ketogenic diet decreases insulin and IGF-1 signaling. “This causes normal cells to enter dormancy, decreasing oxidative damage in normal cells,” Dr. Lemanne said. “There is also suppression of tumor angiogenesis, and thus poor DNA repair of radiation damage in tumor cells (Cancer Metastasis Rev. 2014;33[1]:217-29). Being in ketosis widens the therapeutic window. There are many animal studies which show that the ketogenic diet is helpful in cancer, mainly when combined with other anticancer treatments, such as radiation. Unfortunately, the evidence in humans is very anecdotal.”
One study found that if you feed mice with cancer ketogenic chow versus standard chow, they have a modestly improved survival (a mean of 43 days vs. 33 days; PLoS ONE. 2012;7[5]:e36197). However, when radiation was added to the keto diet, there was a dramatic improvement in survival (P less than 0.001). In fact, 75% survived to 250 days. “That’s pretty spectacular,” Dr. Lemanne said.
A ketogenic diet is standard therapy for several nonmalignant conditions, including glucose transporter 1 deficiency syndrome, pyruvate dehydrogenase deficiency syndrome, and refractory infantile epilepsy. The three major ketone bodies involved in human nutrition are acetoacetate, beta hydroxybutyrate, and acetone. Dr. Lemanne said beta hydroxybutyrate decreases inflammation and inhibits hexadecynoic acids (which induces apoptosis in cancer cells). Beta hydroxybutyrate also increases sirtuins, innate immunity, and seizure threshold; modulates circadian rhythm; and decreases insulin levels, she said.
In one case report from the scientific literature, a 38-year-old male with glioblastoma multiforme was placed on a hypocaloric ketogenic diet (Front Nutr. 2018 Mar 29;5:20). The patient had surgery, radiation, chemotherapy, and hyperbaric oxygen, and was given high doses of green tea extract in an attempt to antagonize glutamine metabolism. Two years after the beginning of his treatment, he was alive and had maintained a good level of tumor regression.
“We’ll see how he does,” said Dr. Lemanne, who was not involved in the report. “In my experience, I have a patient right now with a diagnosis of glioblastoma multiforme. She’s getting a keto diet in combo with intensive chemo, radiation, and surgery. She’s also had some hyperbaric oxygen and IV ozone therapy and is taking repurposed drugs. She has exceeded her expected survival, but she continues to have disease and symptoms. We are by no means out of the woods with this patient. But the keto diet has been quite feasible for her, because she has a lot of family and outside support.”
A ketogenic diet also may benefit patients with cancer cachexia, which is a loss of lean tissue. “Cancer cachexia is not completely understood,” Dr. Lemanne said. “What we know is that it is caused by inflammation created by the tumor itself, and this, in turn results in severe insulin resistance. Therefore, giving more calories as carbohydrate makes the cancer cachexia situation worse. Animal models of cancer cachexia have shown that the ketogenic diet normalizes metabolism and prevents lean tissue loss. Human studies are underway; we’ll see how they turn out.”
She closed her presentation by noting that in copious amounts of animal studies, fasting has been linked to improvements in chemotherapy efficacy and decreased side effects. In one study carried out at the University of Southern California in Los Angeles, volunteers fasted up to 140 hours before chemotherapy and an additional 156 hours afterward (Aging. 2009;1[12]:988-1007). The researchers found that the fasting was well-tolerated.
“The patients had some mild light-headedness, but there were no adverse effects on tumor volume or serum tumor markers,” Dr. Lemanne said. A more recent study of patients on cisplatin found that acaloric fasting led to decreased DNA damage in white blood cells, decreased IFG-1, and better white blood cell counts (BMC Cancer. 2016 Jun 10;16:360). “The benefits are immediate, and the optimal fasting time appears to be 48 hours,” Dr. Lemanne said.
One of her patients is a 64-year-old man on adjuvant cisplatin-based chemotherapy for cholangiocarcinoma. He fasts 24 hours before and 24 hours after each infusion, and has experienced no emesis or nausea. “His immune suppression and anemia are much milder than we expected, and he has not required any treatment for chemotherapy-related side effects,” Dr. Lemanne said. “That’s a big monetary value.”
Fasting 13 hours overnight has been associated with fewer breast cancer-related problems in patients already diagnosed with the disease. Chronic caloric restriction, just cutting calories by 25%-40% daily, has been shown to delay all diseases of aging, including cancer, and is associated with increased longevity in many species. “Chronic caloric restriction is difficult, however, because it results in chronic hunger and weight loss,” she said. “Occasional fasting is superior to chronic caloric restriction because it maintains normal weight, preserves lean muscle mass, enhances tumor sensitivity to chemotherapy and radiotherapy, and diminishes the side effects of chemotherapy.”
Dr. Lemanne reported having no financial disclosures.
SAN DIEGO – When Dawn Lemanne, MD, MPH, meets with cancer patients and their families, the question invariably comes up: “What should I eat?”
“The answer always is, ‘It depends,’” Dr. Lemanne, an oncologist who founded Oregon Integrative Oncology in Ashland, said at Natural Supplements: An Evidence-Based Update, presented by Scripps Center for Integrative Medicine. “The answers are not the same for each of these patients.”
According to Dr. Lemanne, targeted nutrition is evolving as a key component of cancer care. One of the goals of this approach is to decrease mTOR signaling. Normally, mTOR signaling promotes cell proliferation and metabolism; aberrant mTOR signaling can contribute to cancer initiation and progression.
“When mTOR speaks it says, ‘grow,’” said Dr. Lemanne, who is also an assistant professor of clinical medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona in Tucson. This message is meant to be heard by normal tissues, to stimulate normal tissue proliferation, such as in growing children or when a wound needs to be healed.
“However, cancer cells can hear and respond to mTOR’s message,” she said. “Normal cells may listen to mTOR’s ‘grow’ message or not, depending on the task they perform. Once we reach adulthood, we all likely have some precancerous or cancerous cells around, but they’re usually dormant. That’s why once you’re an adult, however, you don’t want too much mTOR signaling, because that might stimulate growth of things you definitely don’t want to grow.”
Having excessive levels of the growth hormone insulin-like growth factor-1 (IGF-1) also appears to play a role in cancer risk. Researchers studying members of a South American clan with Laron dwarfism – an inherited IGF-1 deficiency – found that besides being very short, affected members of this family rarely develop cancer (Cells. 2019;8[6]:596). “They also don’t get diabetes,” Dr. Lemanne said. “What we see in those with Laron dwarfism is that mTOR signaling is missing.”
She went on to note that studying type 2 diabetes gives physicians “a clue as to what dietary measures we might offer our patients in terms of decreasing their risk of dying from cancer or getting cancer.” The most common types of cancer are indeed more common in patients with type 2 diabetes. In addition, once someone with type 2 diabetes is diagnosed with cancer, their prognosis is poorer, compared with a cancer patient without diabetes.
“Metformin is often prescribed to patients with type 2 diabetes because it helps keep blood sugar low,” she said. “What’s fascinating is that diabetics on metformin develop cancer less frequently than diabetics not taking this drug. And also interesting, those diabetics who do develop cancer seem to do better if they’re on metformin before and after diagnosis.”
On the other hand, exogenous insulin therapy given to people with type 2 diabetes doubles the risk of cancer. Consistent with this is the two-decades-old finding that an elevated fasting insulin level also is associated with a poor breast cancer prognosis (J Clin Oncol. 2002 Jan 1;20[1]:42-51). “It’s really important to understand that, in a person destined to become a type 2 diabetic, the level of fasting insulin rises long before fasting glucose becomes abnormally high,” Dr. Lemanne explained. “A normal fasting glucose doesn’t let you off the hook in terms of checking your patient for insulin resistance.
“We will miss diagnosing many patients with dangerous insulin resistance and prediabetes if we don’t check the fasting glucose and the fasting insulin levels together. If the fasting insulin level is high, it’s important to limit carbohydrate intake enough to bring it down permanently, even when the fasting glucose is normal, or the patient is likely at increased risk for developing cancer.”
Two large, prospective randomized trials have examined breast cancer and diet: the Women’s Intervention Study (WINS) and the Women’s Health Eating and Living Study (WHEL). Patients in both trials had early stage breast cancer and were put on low-fat diets. In the end, there was a weak to negligible connection between breast cancer survival and dietary fat restriction. “That kind of shook up the oncology world,” Dr. Lemanne said, “because before these two studies, everyone ‘knew’ that dietary fat was related to breast cancer risk. These studies showed that wasn’t the case at all.”
According to Dr. Lemanne, unexpectedly, moderate carbohydrate restriction has been associated with lower risk of breast cancer recurrence in patients with postmenopausal hormone-receptor expressing breast cancer. Researchers at the University of California, San Diego, conducted a subanalysis of 265 postmenopausal patients with estrogen receptor positive breast cancer from the WHEL cohort (Cancer Epidemiol Biomarkers Prev. 2014 23[7]:1273-9). The recurrence risk was halved in those who cut their carbohydrate intake after diagnosis. The amount of decrease was modest, only 27 grams per day – the equivalent of one banana. “That is on par with a lot of our drugs, and maybe a little bit better,” she said. The effect was strongest if the breast tumor expressed IGF-1 receptor. Dr. Lemanne pointed out that decreasing dietary carbohydrate load was not the only treatment. These patients also had appropriate conventional cancer treatments, including surgery, radiation, and chemotherapy. “If we cut just some of the daily carb load in these patients, they might have a better cancer prognosis,” she said.
Overweight or obese patients with colon cancer also may benefit from moderate carbohydrate restriction. The CALGB 89803 study assessed 1,011 subjects with stage III colon cancer. It found that the subjects in the highest quintile of daily glycemic load and total carbohydrate intake had an increased risk of cancer recurrence and mortality (hazard ratio, 2.26; J Nat Cancer Inst. 2012;104[22]:1702-11). “This is pretty strong evidence that glycemic load and total carbohydrate intake play a role in colon cancer recurrence, but there’s a caveat here,” she said. “The effect was seen only in patients who were overweight or obese.” There was no association between carbohydrate intake and colon cancer recurrence in the absence of overweight or obesity.
Based on existing evidence, she said,
“That’s pretty modest; that’s 400 calories of carbohydrates per day,” Dr. Lemanne said. “I tell patients that they can have fruit, starchy vegetables, and even very small amounts of healthy whole grains, although I’m not a fan of grains due to the heavy carbohydrate load. All those things are OK. We’re not talking about jelly beans and white sugar.
“I also have them measure their fasting glucose each day, because different people have different blood glucose responses to the same food.” The goals she aims for with many of her patients are a fasting morning glucose between 79 and 83 mg/dL consistently, an HbA1c of 5.4 or less, and a BMI of 24.9 kg/m2 or less. “This set of goals, however, has to be individualized,” she said.
The ketogenic diet is another form of carb restriction, “but it’s much more drastic,” Dr. Lemanne said. “Most people require a carbohydrate load below 30 grams a day to enter a state of ketosis. But ketosis lowers the blood sugar and dampens the mTOR signaling.”
Evidence is emerging to support the use of a ketogenic diet as an adjunct to radiation therapy and as part of a complete course of treatment for glioblastoma multiforme and cancer cachexia. As an adjunct to radiation, a ketogenic diet decreases insulin and IGF-1 signaling. “This causes normal cells to enter dormancy, decreasing oxidative damage in normal cells,” Dr. Lemanne said. “There is also suppression of tumor angiogenesis, and thus poor DNA repair of radiation damage in tumor cells (Cancer Metastasis Rev. 2014;33[1]:217-29). Being in ketosis widens the therapeutic window. There are many animal studies which show that the ketogenic diet is helpful in cancer, mainly when combined with other anticancer treatments, such as radiation. Unfortunately, the evidence in humans is very anecdotal.”
One study found that if you feed mice with cancer ketogenic chow versus standard chow, they have a modestly improved survival (a mean of 43 days vs. 33 days; PLoS ONE. 2012;7[5]:e36197). However, when radiation was added to the keto diet, there was a dramatic improvement in survival (P less than 0.001). In fact, 75% survived to 250 days. “That’s pretty spectacular,” Dr. Lemanne said.
A ketogenic diet is standard therapy for several nonmalignant conditions, including glucose transporter 1 deficiency syndrome, pyruvate dehydrogenase deficiency syndrome, and refractory infantile epilepsy. The three major ketone bodies involved in human nutrition are acetoacetate, beta hydroxybutyrate, and acetone. Dr. Lemanne said beta hydroxybutyrate decreases inflammation and inhibits hexadecynoic acids (which induces apoptosis in cancer cells). Beta hydroxybutyrate also increases sirtuins, innate immunity, and seizure threshold; modulates circadian rhythm; and decreases insulin levels, she said.
In one case report from the scientific literature, a 38-year-old male with glioblastoma multiforme was placed on a hypocaloric ketogenic diet (Front Nutr. 2018 Mar 29;5:20). The patient had surgery, radiation, chemotherapy, and hyperbaric oxygen, and was given high doses of green tea extract in an attempt to antagonize glutamine metabolism. Two years after the beginning of his treatment, he was alive and had maintained a good level of tumor regression.
“We’ll see how he does,” said Dr. Lemanne, who was not involved in the report. “In my experience, I have a patient right now with a diagnosis of glioblastoma multiforme. She’s getting a keto diet in combo with intensive chemo, radiation, and surgery. She’s also had some hyperbaric oxygen and IV ozone therapy and is taking repurposed drugs. She has exceeded her expected survival, but she continues to have disease and symptoms. We are by no means out of the woods with this patient. But the keto diet has been quite feasible for her, because she has a lot of family and outside support.”
A ketogenic diet also may benefit patients with cancer cachexia, which is a loss of lean tissue. “Cancer cachexia is not completely understood,” Dr. Lemanne said. “What we know is that it is caused by inflammation created by the tumor itself, and this, in turn results in severe insulin resistance. Therefore, giving more calories as carbohydrate makes the cancer cachexia situation worse. Animal models of cancer cachexia have shown that the ketogenic diet normalizes metabolism and prevents lean tissue loss. Human studies are underway; we’ll see how they turn out.”
She closed her presentation by noting that in copious amounts of animal studies, fasting has been linked to improvements in chemotherapy efficacy and decreased side effects. In one study carried out at the University of Southern California in Los Angeles, volunteers fasted up to 140 hours before chemotherapy and an additional 156 hours afterward (Aging. 2009;1[12]:988-1007). The researchers found that the fasting was well-tolerated.
“The patients had some mild light-headedness, but there were no adverse effects on tumor volume or serum tumor markers,” Dr. Lemanne said. A more recent study of patients on cisplatin found that acaloric fasting led to decreased DNA damage in white blood cells, decreased IFG-1, and better white blood cell counts (BMC Cancer. 2016 Jun 10;16:360). “The benefits are immediate, and the optimal fasting time appears to be 48 hours,” Dr. Lemanne said.
One of her patients is a 64-year-old man on adjuvant cisplatin-based chemotherapy for cholangiocarcinoma. He fasts 24 hours before and 24 hours after each infusion, and has experienced no emesis or nausea. “His immune suppression and anemia are much milder than we expected, and he has not required any treatment for chemotherapy-related side effects,” Dr. Lemanne said. “That’s a big monetary value.”
Fasting 13 hours overnight has been associated with fewer breast cancer-related problems in patients already diagnosed with the disease. Chronic caloric restriction, just cutting calories by 25%-40% daily, has been shown to delay all diseases of aging, including cancer, and is associated with increased longevity in many species. “Chronic caloric restriction is difficult, however, because it results in chronic hunger and weight loss,” she said. “Occasional fasting is superior to chronic caloric restriction because it maintains normal weight, preserves lean muscle mass, enhances tumor sensitivity to chemotherapy and radiotherapy, and diminishes the side effects of chemotherapy.”
Dr. Lemanne reported having no financial disclosures.
SAN DIEGO – When Dawn Lemanne, MD, MPH, meets with cancer patients and their families, the question invariably comes up: “What should I eat?”
“The answer always is, ‘It depends,’” Dr. Lemanne, an oncologist who founded Oregon Integrative Oncology in Ashland, said at Natural Supplements: An Evidence-Based Update, presented by Scripps Center for Integrative Medicine. “The answers are not the same for each of these patients.”
According to Dr. Lemanne, targeted nutrition is evolving as a key component of cancer care. One of the goals of this approach is to decrease mTOR signaling. Normally, mTOR signaling promotes cell proliferation and metabolism; aberrant mTOR signaling can contribute to cancer initiation and progression.
“When mTOR speaks it says, ‘grow,’” said Dr. Lemanne, who is also an assistant professor of clinical medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona in Tucson. This message is meant to be heard by normal tissues, to stimulate normal tissue proliferation, such as in growing children or when a wound needs to be healed.
“However, cancer cells can hear and respond to mTOR’s message,” she said. “Normal cells may listen to mTOR’s ‘grow’ message or not, depending on the task they perform. Once we reach adulthood, we all likely have some precancerous or cancerous cells around, but they’re usually dormant. That’s why once you’re an adult, however, you don’t want too much mTOR signaling, because that might stimulate growth of things you definitely don’t want to grow.”
Having excessive levels of the growth hormone insulin-like growth factor-1 (IGF-1) also appears to play a role in cancer risk. Researchers studying members of a South American clan with Laron dwarfism – an inherited IGF-1 deficiency – found that besides being very short, affected members of this family rarely develop cancer (Cells. 2019;8[6]:596). “They also don’t get diabetes,” Dr. Lemanne said. “What we see in those with Laron dwarfism is that mTOR signaling is missing.”
She went on to note that studying type 2 diabetes gives physicians “a clue as to what dietary measures we might offer our patients in terms of decreasing their risk of dying from cancer or getting cancer.” The most common types of cancer are indeed more common in patients with type 2 diabetes. In addition, once someone with type 2 diabetes is diagnosed with cancer, their prognosis is poorer, compared with a cancer patient without diabetes.
“Metformin is often prescribed to patients with type 2 diabetes because it helps keep blood sugar low,” she said. “What’s fascinating is that diabetics on metformin develop cancer less frequently than diabetics not taking this drug. And also interesting, those diabetics who do develop cancer seem to do better if they’re on metformin before and after diagnosis.”
On the other hand, exogenous insulin therapy given to people with type 2 diabetes doubles the risk of cancer. Consistent with this is the two-decades-old finding that an elevated fasting insulin level also is associated with a poor breast cancer prognosis (J Clin Oncol. 2002 Jan 1;20[1]:42-51). “It’s really important to understand that, in a person destined to become a type 2 diabetic, the level of fasting insulin rises long before fasting glucose becomes abnormally high,” Dr. Lemanne explained. “A normal fasting glucose doesn’t let you off the hook in terms of checking your patient for insulin resistance.
“We will miss diagnosing many patients with dangerous insulin resistance and prediabetes if we don’t check the fasting glucose and the fasting insulin levels together. If the fasting insulin level is high, it’s important to limit carbohydrate intake enough to bring it down permanently, even when the fasting glucose is normal, or the patient is likely at increased risk for developing cancer.”
Two large, prospective randomized trials have examined breast cancer and diet: the Women’s Intervention Study (WINS) and the Women’s Health Eating and Living Study (WHEL). Patients in both trials had early stage breast cancer and were put on low-fat diets. In the end, there was a weak to negligible connection between breast cancer survival and dietary fat restriction. “That kind of shook up the oncology world,” Dr. Lemanne said, “because before these two studies, everyone ‘knew’ that dietary fat was related to breast cancer risk. These studies showed that wasn’t the case at all.”
According to Dr. Lemanne, unexpectedly, moderate carbohydrate restriction has been associated with lower risk of breast cancer recurrence in patients with postmenopausal hormone-receptor expressing breast cancer. Researchers at the University of California, San Diego, conducted a subanalysis of 265 postmenopausal patients with estrogen receptor positive breast cancer from the WHEL cohort (Cancer Epidemiol Biomarkers Prev. 2014 23[7]:1273-9). The recurrence risk was halved in those who cut their carbohydrate intake after diagnosis. The amount of decrease was modest, only 27 grams per day – the equivalent of one banana. “That is on par with a lot of our drugs, and maybe a little bit better,” she said. The effect was strongest if the breast tumor expressed IGF-1 receptor. Dr. Lemanne pointed out that decreasing dietary carbohydrate load was not the only treatment. These patients also had appropriate conventional cancer treatments, including surgery, radiation, and chemotherapy. “If we cut just some of the daily carb load in these patients, they might have a better cancer prognosis,” she said.
Overweight or obese patients with colon cancer also may benefit from moderate carbohydrate restriction. The CALGB 89803 study assessed 1,011 subjects with stage III colon cancer. It found that the subjects in the highest quintile of daily glycemic load and total carbohydrate intake had an increased risk of cancer recurrence and mortality (hazard ratio, 2.26; J Nat Cancer Inst. 2012;104[22]:1702-11). “This is pretty strong evidence that glycemic load and total carbohydrate intake play a role in colon cancer recurrence, but there’s a caveat here,” she said. “The effect was seen only in patients who were overweight or obese.” There was no association between carbohydrate intake and colon cancer recurrence in the absence of overweight or obesity.
Based on existing evidence, she said,
“That’s pretty modest; that’s 400 calories of carbohydrates per day,” Dr. Lemanne said. “I tell patients that they can have fruit, starchy vegetables, and even very small amounts of healthy whole grains, although I’m not a fan of grains due to the heavy carbohydrate load. All those things are OK. We’re not talking about jelly beans and white sugar.
“I also have them measure their fasting glucose each day, because different people have different blood glucose responses to the same food.” The goals she aims for with many of her patients are a fasting morning glucose between 79 and 83 mg/dL consistently, an HbA1c of 5.4 or less, and a BMI of 24.9 kg/m2 or less. “This set of goals, however, has to be individualized,” she said.
The ketogenic diet is another form of carb restriction, “but it’s much more drastic,” Dr. Lemanne said. “Most people require a carbohydrate load below 30 grams a day to enter a state of ketosis. But ketosis lowers the blood sugar and dampens the mTOR signaling.”
Evidence is emerging to support the use of a ketogenic diet as an adjunct to radiation therapy and as part of a complete course of treatment for glioblastoma multiforme and cancer cachexia. As an adjunct to radiation, a ketogenic diet decreases insulin and IGF-1 signaling. “This causes normal cells to enter dormancy, decreasing oxidative damage in normal cells,” Dr. Lemanne said. “There is also suppression of tumor angiogenesis, and thus poor DNA repair of radiation damage in tumor cells (Cancer Metastasis Rev. 2014;33[1]:217-29). Being in ketosis widens the therapeutic window. There are many animal studies which show that the ketogenic diet is helpful in cancer, mainly when combined with other anticancer treatments, such as radiation. Unfortunately, the evidence in humans is very anecdotal.”
One study found that if you feed mice with cancer ketogenic chow versus standard chow, they have a modestly improved survival (a mean of 43 days vs. 33 days; PLoS ONE. 2012;7[5]:e36197). However, when radiation was added to the keto diet, there was a dramatic improvement in survival (P less than 0.001). In fact, 75% survived to 250 days. “That’s pretty spectacular,” Dr. Lemanne said.
A ketogenic diet is standard therapy for several nonmalignant conditions, including glucose transporter 1 deficiency syndrome, pyruvate dehydrogenase deficiency syndrome, and refractory infantile epilepsy. The three major ketone bodies involved in human nutrition are acetoacetate, beta hydroxybutyrate, and acetone. Dr. Lemanne said beta hydroxybutyrate decreases inflammation and inhibits hexadecynoic acids (which induces apoptosis in cancer cells). Beta hydroxybutyrate also increases sirtuins, innate immunity, and seizure threshold; modulates circadian rhythm; and decreases insulin levels, she said.
In one case report from the scientific literature, a 38-year-old male with glioblastoma multiforme was placed on a hypocaloric ketogenic diet (Front Nutr. 2018 Mar 29;5:20). The patient had surgery, radiation, chemotherapy, and hyperbaric oxygen, and was given high doses of green tea extract in an attempt to antagonize glutamine metabolism. Two years after the beginning of his treatment, he was alive and had maintained a good level of tumor regression.
“We’ll see how he does,” said Dr. Lemanne, who was not involved in the report. “In my experience, I have a patient right now with a diagnosis of glioblastoma multiforme. She’s getting a keto diet in combo with intensive chemo, radiation, and surgery. She’s also had some hyperbaric oxygen and IV ozone therapy and is taking repurposed drugs. She has exceeded her expected survival, but she continues to have disease and symptoms. We are by no means out of the woods with this patient. But the keto diet has been quite feasible for her, because she has a lot of family and outside support.”
A ketogenic diet also may benefit patients with cancer cachexia, which is a loss of lean tissue. “Cancer cachexia is not completely understood,” Dr. Lemanne said. “What we know is that it is caused by inflammation created by the tumor itself, and this, in turn results in severe insulin resistance. Therefore, giving more calories as carbohydrate makes the cancer cachexia situation worse. Animal models of cancer cachexia have shown that the ketogenic diet normalizes metabolism and prevents lean tissue loss. Human studies are underway; we’ll see how they turn out.”
She closed her presentation by noting that in copious amounts of animal studies, fasting has been linked to improvements in chemotherapy efficacy and decreased side effects. In one study carried out at the University of Southern California in Los Angeles, volunteers fasted up to 140 hours before chemotherapy and an additional 156 hours afterward (Aging. 2009;1[12]:988-1007). The researchers found that the fasting was well-tolerated.
“The patients had some mild light-headedness, but there were no adverse effects on tumor volume or serum tumor markers,” Dr. Lemanne said. A more recent study of patients on cisplatin found that acaloric fasting led to decreased DNA damage in white blood cells, decreased IFG-1, and better white blood cell counts (BMC Cancer. 2016 Jun 10;16:360). “The benefits are immediate, and the optimal fasting time appears to be 48 hours,” Dr. Lemanne said.
One of her patients is a 64-year-old man on adjuvant cisplatin-based chemotherapy for cholangiocarcinoma. He fasts 24 hours before and 24 hours after each infusion, and has experienced no emesis or nausea. “His immune suppression and anemia are much milder than we expected, and he has not required any treatment for chemotherapy-related side effects,” Dr. Lemanne said. “That’s a big monetary value.”
Fasting 13 hours overnight has been associated with fewer breast cancer-related problems in patients already diagnosed with the disease. Chronic caloric restriction, just cutting calories by 25%-40% daily, has been shown to delay all diseases of aging, including cancer, and is associated with increased longevity in many species. “Chronic caloric restriction is difficult, however, because it results in chronic hunger and weight loss,” she said. “Occasional fasting is superior to chronic caloric restriction because it maintains normal weight, preserves lean muscle mass, enhances tumor sensitivity to chemotherapy and radiotherapy, and diminishes the side effects of chemotherapy.”
Dr. Lemanne reported having no financial disclosures.
REPORTING FROM A NATURAL SUPPLEMENTS UPDATE