Endocrinology

The global burden of thyroid cancer is substantial, and incidence rates are increasing in many developed countries, including the Unites States, concluded a new analysis based on 30 years of observational data.

“We report overall increases in the burden of thyroid cancer across the majority of EU15+ countries between 1990 and 2019, evidenced by plateaus in incidence rates and reductions in mortality and DALY [disability-adjusted life-years] rates,” the authors reported.

“However, in a number of countries, including the U.S., there are unfavorable increasing mortality and DALY trends over this time period ... [and] a better understanding of the trends in the disease burden of thyroid cancer may help to inform future health system planning,” they added.

The study was published online March 10, 2022, in JAMA Otolaryngology–Head & Neck Surgery.
 

Trends in thyroid cancer

For the analysis, James Schuster-Bruce, MBChB, from St. George’s University Hospital NHS Foundation Trust, London, and colleagues compared trends in thyroid cancer across 30 years of follow-up among 15 countries of the (pre-2004) European Union as well as those in the United States, Australia, Canada, and Norway (EU15+).

Data from the Global Burden of Disease study database were used to track these trends. “We extracted age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and DALYs for thyroid cancer from EU15+ countries between 1990 and 2019 using the dedicated GBD study results tool,” the investigators explained.

In 2019, ASIRs were highest in Italy at 6.36 per 100,000 population, followed by the United States at a rate of 5.59 per 100,000 population – although incidence rates of thyroid cancer have actually recently decreased in U.S. women, they noted.

“Thirteen of 19 countries showed an average annual percentage increase in ASIR across the study period,” the investigators added. Out of all the EU15+ countries, the average annual percentage change (AAPC) was the highest in Australia at 2.5 per 100,000 population and the United States at 1.2 per 100,000.

On the other hand, a largely plateauing trend in incidence rates across the majority of EU15+ nations has been observed since 1990, as reflected by incidence rates ranging from –0.8 to 0.8 per 100,000 in the most recent period, the researchers added. ASMRs ranged from a 0.40 per 100,000 in Greece to 0.57 per 100,000 in Luxembourg.

In the United States, the ASMR in 2019 was 0.43 per 100,000 population while the ASMR was the lowest in the United Kingdom in the same year at 0.38 per 100,000 population.

Australia, Denmark, and the United States were the only countries showing positive AAPC changes, the team observed. For example, in the most recent period to 2019, Denmark and Australia had reductions in ASMR trends, whereas in the United States, the trend was toward increasing ASMRs 

In 2019, the DALYs of the EU15+ nations ranged from 9.63 per 100,000 in the United Kingdom to 14.46 per 100,000 in Luxembourg. In the most recent period, a downward trend in DALYs was observed in Australia and Denmark while it plateaued in the United States.

“Overall, we identified improvements in thyroid cancer mortality and DALYs, but overall increases in thyroid cancer incidence in EU15+ countries over the past 3 decades,” the investigators commented.

It has been widely suggested that improvements in diagnostic techniques have contributed significantly to increasing incidence rates of thyroid cancer, but there is concern about overdiagnosis.  Newer diagnostic techniques detect significant numbers of slow-growing, subclinical papillary thyroid cancers that make up at least one quarter of all thyroid cancer subtypes, the authors pointed out.

“It has therefore been suggested that an increase in subclinical disease has inflated the data to look more substantial than the clinical reality,” the authors wrote. However, they insisted that overdiagnosis alone is unlikely to account entirely for increasing incidence trends in the current analysis.

Rather, their concern for countries with high incidence rates of thyroid cancer is the surveillance burden of disease that does not affect mortality. “Close observation of future time trends in thyroid cancer disease burden should be performed in the context of recent changes in international clinical practice guidelines, which have suggested more conservative diagnostic and management strategies,” the authors suggested.

“In the context of the more conservative treatment guidelines and reported increase in true disease, it is important to closely observe mortality and DALYs over the coming years to ensure optimum thyroid cancer management in these nations,” they added.

The study had no specific funding. Dr. Schuster-Bruce disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The global burden of thyroid cancer is substantial, and incidence rates are increasing in many developed countries, including the Unites States, concluded a new analysis based on 30 years of observational data.

“We report overall increases in the burden of thyroid cancer across the majority of EU15+ countries between 1990 and 2019, evidenced by plateaus in incidence rates and reductions in mortality and DALY [disability-adjusted life-years] rates,” the authors reported.

“However, in a number of countries, including the U.S., there are unfavorable increasing mortality and DALY trends over this time period ... [and] a better understanding of the trends in the disease burden of thyroid cancer may help to inform future health system planning,” they added.

The study was published online March 10, 2022, in JAMA Otolaryngology–Head & Neck Surgery.
 

Trends in thyroid cancer

For the analysis, James Schuster-Bruce, MBChB, from St. George’s University Hospital NHS Foundation Trust, London, and colleagues compared trends in thyroid cancer across 30 years of follow-up among 15 countries of the (pre-2004) European Union as well as those in the United States, Australia, Canada, and Norway (EU15+).

Data from the Global Burden of Disease study database were used to track these trends. “We extracted age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and DALYs for thyroid cancer from EU15+ countries between 1990 and 2019 using the dedicated GBD study results tool,” the investigators explained.

In 2019, ASIRs were highest in Italy at 6.36 per 100,000 population, followed by the United States at a rate of 5.59 per 100,000 population – although incidence rates of thyroid cancer have actually recently decreased in U.S. women, they noted.

“Thirteen of 19 countries showed an average annual percentage increase in ASIR across the study period,” the investigators added. Out of all the EU15+ countries, the average annual percentage change (AAPC) was the highest in Australia at 2.5 per 100,000 population and the United States at 1.2 per 100,000.

On the other hand, a largely plateauing trend in incidence rates across the majority of EU15+ nations has been observed since 1990, as reflected by incidence rates ranging from –0.8 to 0.8 per 100,000 in the most recent period, the researchers added. ASMRs ranged from a 0.40 per 100,000 in Greece to 0.57 per 100,000 in Luxembourg.

In the United States, the ASMR in 2019 was 0.43 per 100,000 population while the ASMR was the lowest in the United Kingdom in the same year at 0.38 per 100,000 population.

Australia, Denmark, and the United States were the only countries showing positive AAPC changes, the team observed. For example, in the most recent period to 2019, Denmark and Australia had reductions in ASMR trends, whereas in the United States, the trend was toward increasing ASMRs 

In 2019, the DALYs of the EU15+ nations ranged from 9.63 per 100,000 in the United Kingdom to 14.46 per 100,000 in Luxembourg. In the most recent period, a downward trend in DALYs was observed in Australia and Denmark while it plateaued in the United States.

“Overall, we identified improvements in thyroid cancer mortality and DALYs, but overall increases in thyroid cancer incidence in EU15+ countries over the past 3 decades,” the investigators commented.

It has been widely suggested that improvements in diagnostic techniques have contributed significantly to increasing incidence rates of thyroid cancer, but there is concern about overdiagnosis.  Newer diagnostic techniques detect significant numbers of slow-growing, subclinical papillary thyroid cancers that make up at least one quarter of all thyroid cancer subtypes, the authors pointed out.

“It has therefore been suggested that an increase in subclinical disease has inflated the data to look more substantial than the clinical reality,” the authors wrote. However, they insisted that overdiagnosis alone is unlikely to account entirely for increasing incidence trends in the current analysis.

Rather, their concern for countries with high incidence rates of thyroid cancer is the surveillance burden of disease that does not affect mortality. “Close observation of future time trends in thyroid cancer disease burden should be performed in the context of recent changes in international clinical practice guidelines, which have suggested more conservative diagnostic and management strategies,” the authors suggested.

“In the context of the more conservative treatment guidelines and reported increase in true disease, it is important to closely observe mortality and DALYs over the coming years to ensure optimum thyroid cancer management in these nations,” they added.

The study had no specific funding. Dr. Schuster-Bruce disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The global burden of thyroid cancer is substantial, and incidence rates are increasing in many developed countries, including the Unites States, concluded a new analysis based on 30 years of observational data.

“We report overall increases in the burden of thyroid cancer across the majority of EU15+ countries between 1990 and 2019, evidenced by plateaus in incidence rates and reductions in mortality and DALY [disability-adjusted life-years] rates,” the authors reported.

“However, in a number of countries, including the U.S., there are unfavorable increasing mortality and DALY trends over this time period ... [and] a better understanding of the trends in the disease burden of thyroid cancer may help to inform future health system planning,” they added.

The study was published online March 10, 2022, in JAMA Otolaryngology–Head & Neck Surgery.
 

Trends in thyroid cancer

For the analysis, James Schuster-Bruce, MBChB, from St. George’s University Hospital NHS Foundation Trust, London, and colleagues compared trends in thyroid cancer across 30 years of follow-up among 15 countries of the (pre-2004) European Union as well as those in the United States, Australia, Canada, and Norway (EU15+).

Data from the Global Burden of Disease study database were used to track these trends. “We extracted age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and DALYs for thyroid cancer from EU15+ countries between 1990 and 2019 using the dedicated GBD study results tool,” the investigators explained.

In 2019, ASIRs were highest in Italy at 6.36 per 100,000 population, followed by the United States at a rate of 5.59 per 100,000 population – although incidence rates of thyroid cancer have actually recently decreased in U.S. women, they noted.

“Thirteen of 19 countries showed an average annual percentage increase in ASIR across the study period,” the investigators added. Out of all the EU15+ countries, the average annual percentage change (AAPC) was the highest in Australia at 2.5 per 100,000 population and the United States at 1.2 per 100,000.

On the other hand, a largely plateauing trend in incidence rates across the majority of EU15+ nations has been observed since 1990, as reflected by incidence rates ranging from –0.8 to 0.8 per 100,000 in the most recent period, the researchers added. ASMRs ranged from a 0.40 per 100,000 in Greece to 0.57 per 100,000 in Luxembourg.

In the United States, the ASMR in 2019 was 0.43 per 100,000 population while the ASMR was the lowest in the United Kingdom in the same year at 0.38 per 100,000 population.

Australia, Denmark, and the United States were the only countries showing positive AAPC changes, the team observed. For example, in the most recent period to 2019, Denmark and Australia had reductions in ASMR trends, whereas in the United States, the trend was toward increasing ASMRs 

In 2019, the DALYs of the EU15+ nations ranged from 9.63 per 100,000 in the United Kingdom to 14.46 per 100,000 in Luxembourg. In the most recent period, a downward trend in DALYs was observed in Australia and Denmark while it plateaued in the United States.

“Overall, we identified improvements in thyroid cancer mortality and DALYs, but overall increases in thyroid cancer incidence in EU15+ countries over the past 3 decades,” the investigators commented.

It has been widely suggested that improvements in diagnostic techniques have contributed significantly to increasing incidence rates of thyroid cancer, but there is concern about overdiagnosis.  Newer diagnostic techniques detect significant numbers of slow-growing, subclinical papillary thyroid cancers that make up at least one quarter of all thyroid cancer subtypes, the authors pointed out.

“It has therefore been suggested that an increase in subclinical disease has inflated the data to look more substantial than the clinical reality,” the authors wrote. However, they insisted that overdiagnosis alone is unlikely to account entirely for increasing incidence trends in the current analysis.

Rather, their concern for countries with high incidence rates of thyroid cancer is the surveillance burden of disease that does not affect mortality. “Close observation of future time trends in thyroid cancer disease burden should be performed in the context of recent changes in international clinical practice guidelines, which have suggested more conservative diagnostic and management strategies,” the authors suggested.

“In the context of the more conservative treatment guidelines and reported increase in true disease, it is important to closely observe mortality and DALYs over the coming years to ensure optimum thyroid cancer management in these nations,” they added.

The study had no specific funding. Dr. Schuster-Bruce disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A genomic study has revealed new insights into the function of anti-Müllerian hormone (AMH) in the context of reproductive biology and fertility.

Insights into the physiological, and potentially therapeutic, function were identified based on data from single-cell RNA sequencing, derived from transcriptomic analysis and immunolabeling of antral follicles.

“The specific contribution of elevated AMH to the molecular pathology of polycystic ovary syndrome (PCOS) and its defining clinical features is unclear, as no study, to date, has examined the effect of chronically elevated AMH in an experimentally controlled in vivo model,” study author Limor Man, MD, of Weill Cornell Medicine, New York, and colleagues wrote. The group’s findings were published in Science Advances.

The researchers used ovarian cortical xenografts with cotransplantation of engineered endothelial cells to examine the effect of chronic paracrine AMH stimulus on human folliculogenesis.

They cotransplanted human ovarian cortex with control or AMH-expressing endothelial cells in immunocompromised mice and recovered antral follicles for purification and subsequent analysis. Overall, 38 antral follicles were observed (19 control and 19 AMH) at long-term intervals, defined as intervals greater than 10 weeks.

The researchers found that long-term xenografts showed an accelerated growth rate in the setting of chronically elevated AMH and exhibited a molecular signature indicative of more advanced stages of follicle maturation, including that of luteinization.

In mice, exogenous AMH follicles showed a decreased ratio of primordial to growing follicles and antral follicles of increased diameter.

In addition, transcriptomic and immunolabeling analyses revealed that chronic high AMH had a marked influence on the growth and transcriptomic signature of antral-stage follicles, with a universal increase in factors related to the synthesis and/or metabolism of cholesterol and sex steroid hormones, as well as early expression of factors often seen at later stages of folliculogenesis.

“These data decouple elevated AMH from the metabolic and hyperandrogenic conditions that define PCOS and suggest that chronically elevated AMH induces a molecular cascade that contributes, at least in part, to the anovulatory phenotype in these patients,” the researchers wrote.

Furthermore, they found evidence to suggest that chronic high AMH can induce expression of the luteinizing hormone receptor at earlier stages of folliculogenesis, thereby worsening the disruptive effect of elevated luteinizing hormone from the pituitary.

“[These] findings underscore the broad influence of AMH on transcriptional activity and maturation state of follicles and support an independent role for dysregulation of AMH signaling in driving anovulation in women with PCOS,” they wrote.

While these findings are intriguing, the researchers cautioned against drawing conclusions from the study since elevated AMH is almost always seen in combination with one or more symptomatic hallmarks in PCOS.

“Despite [some] limitations, [our] analysis provides a deep and high-resolution examination of AMH action on human folliculogenesis and suggests a prominent effect on antral follicle maturation,” they explained.
 

Expert perspective

“From age 25, AMH levels begin their decline until reaching undetectable levels at menopause,” Mark P. Trolice, MD, director of the IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando, said in an interview. “Women with PCOS experience a chronic and frustrating pathophysiologic problem whose origins and mechanism have evaded researchers for decades.

“As AMH elevations in utero may contribute to fetal susceptibility to PCOS, this study provides another potential link by suggesting that chronically elevated AMH induces anovulation,” he added. “We await, with great anticipation, future clinical studies to potentially further illustrate the apparent and intriguing role of AMH in the development of PCOS.”

This study was supported by the Queenie Victorina Neri Scholarship and a Research Grant from the American Society for Reproductive Medicine. One author reported financial relationships with Oviva Therapeutics; no other conflicts of interest were reported.

A genomic study has revealed new insights into the function of anti-Müllerian hormone (AMH) in the context of reproductive biology and fertility.

Insights into the physiological, and potentially therapeutic, function were identified based on data from single-cell RNA sequencing, derived from transcriptomic analysis and immunolabeling of antral follicles.

“The specific contribution of elevated AMH to the molecular pathology of polycystic ovary syndrome (PCOS) and its defining clinical features is unclear, as no study, to date, has examined the effect of chronically elevated AMH in an experimentally controlled in vivo model,” study author Limor Man, MD, of Weill Cornell Medicine, New York, and colleagues wrote. The group’s findings were published in Science Advances.

The researchers used ovarian cortical xenografts with cotransplantation of engineered endothelial cells to examine the effect of chronic paracrine AMH stimulus on human folliculogenesis.

They cotransplanted human ovarian cortex with control or AMH-expressing endothelial cells in immunocompromised mice and recovered antral follicles for purification and subsequent analysis. Overall, 38 antral follicles were observed (19 control and 19 AMH) at long-term intervals, defined as intervals greater than 10 weeks.

The researchers found that long-term xenografts showed an accelerated growth rate in the setting of chronically elevated AMH and exhibited a molecular signature indicative of more advanced stages of follicle maturation, including that of luteinization.

In mice, exogenous AMH follicles showed a decreased ratio of primordial to growing follicles and antral follicles of increased diameter.

In addition, transcriptomic and immunolabeling analyses revealed that chronic high AMH had a marked influence on the growth and transcriptomic signature of antral-stage follicles, with a universal increase in factors related to the synthesis and/or metabolism of cholesterol and sex steroid hormones, as well as early expression of factors often seen at later stages of folliculogenesis.

“These data decouple elevated AMH from the metabolic and hyperandrogenic conditions that define PCOS and suggest that chronically elevated AMH induces a molecular cascade that contributes, at least in part, to the anovulatory phenotype in these patients,” the researchers wrote.

Furthermore, they found evidence to suggest that chronic high AMH can induce expression of the luteinizing hormone receptor at earlier stages of folliculogenesis, thereby worsening the disruptive effect of elevated luteinizing hormone from the pituitary.

“[These] findings underscore the broad influence of AMH on transcriptional activity and maturation state of follicles and support an independent role for dysregulation of AMH signaling in driving anovulation in women with PCOS,” they wrote.

While these findings are intriguing, the researchers cautioned against drawing conclusions from the study since elevated AMH is almost always seen in combination with one or more symptomatic hallmarks in PCOS.

“Despite [some] limitations, [our] analysis provides a deep and high-resolution examination of AMH action on human folliculogenesis and suggests a prominent effect on antral follicle maturation,” they explained.
 

Expert perspective

“From age 25, AMH levels begin their decline until reaching undetectable levels at menopause,” Mark P. Trolice, MD, director of the IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando, said in an interview. “Women with PCOS experience a chronic and frustrating pathophysiologic problem whose origins and mechanism have evaded researchers for decades.

“As AMH elevations in utero may contribute to fetal susceptibility to PCOS, this study provides another potential link by suggesting that chronically elevated AMH induces anovulation,” he added. “We await, with great anticipation, future clinical studies to potentially further illustrate the apparent and intriguing role of AMH in the development of PCOS.”

This study was supported by the Queenie Victorina Neri Scholarship and a Research Grant from the American Society for Reproductive Medicine. One author reported financial relationships with Oviva Therapeutics; no other conflicts of interest were reported.

A genomic study has revealed new insights into the function of anti-Müllerian hormone (AMH) in the context of reproductive biology and fertility.

Insights into the physiological, and potentially therapeutic, function were identified based on data from single-cell RNA sequencing, derived from transcriptomic analysis and immunolabeling of antral follicles.

“The specific contribution of elevated AMH to the molecular pathology of polycystic ovary syndrome (PCOS) and its defining clinical features is unclear, as no study, to date, has examined the effect of chronically elevated AMH in an experimentally controlled in vivo model,” study author Limor Man, MD, of Weill Cornell Medicine, New York, and colleagues wrote. The group’s findings were published in Science Advances.

The researchers used ovarian cortical xenografts with cotransplantation of engineered endothelial cells to examine the effect of chronic paracrine AMH stimulus on human folliculogenesis.

They cotransplanted human ovarian cortex with control or AMH-expressing endothelial cells in immunocompromised mice and recovered antral follicles for purification and subsequent analysis. Overall, 38 antral follicles were observed (19 control and 19 AMH) at long-term intervals, defined as intervals greater than 10 weeks.

The researchers found that long-term xenografts showed an accelerated growth rate in the setting of chronically elevated AMH and exhibited a molecular signature indicative of more advanced stages of follicle maturation, including that of luteinization.

In mice, exogenous AMH follicles showed a decreased ratio of primordial to growing follicles and antral follicles of increased diameter.

In addition, transcriptomic and immunolabeling analyses revealed that chronic high AMH had a marked influence on the growth and transcriptomic signature of antral-stage follicles, with a universal increase in factors related to the synthesis and/or metabolism of cholesterol and sex steroid hormones, as well as early expression of factors often seen at later stages of folliculogenesis.

“These data decouple elevated AMH from the metabolic and hyperandrogenic conditions that define PCOS and suggest that chronically elevated AMH induces a molecular cascade that contributes, at least in part, to the anovulatory phenotype in these patients,” the researchers wrote.

Furthermore, they found evidence to suggest that chronic high AMH can induce expression of the luteinizing hormone receptor at earlier stages of folliculogenesis, thereby worsening the disruptive effect of elevated luteinizing hormone from the pituitary.

“[These] findings underscore the broad influence of AMH on transcriptional activity and maturation state of follicles and support an independent role for dysregulation of AMH signaling in driving anovulation in women with PCOS,” they wrote.

While these findings are intriguing, the researchers cautioned against drawing conclusions from the study since elevated AMH is almost always seen in combination with one or more symptomatic hallmarks in PCOS.

“Despite [some] limitations, [our] analysis provides a deep and high-resolution examination of AMH action on human folliculogenesis and suggests a prominent effect on antral follicle maturation,” they explained.
 

Expert perspective

“From age 25, AMH levels begin their decline until reaching undetectable levels at menopause,” Mark P. Trolice, MD, director of the IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando, said in an interview. “Women with PCOS experience a chronic and frustrating pathophysiologic problem whose origins and mechanism have evaded researchers for decades.

“As AMH elevations in utero may contribute to fetal susceptibility to PCOS, this study provides another potential link by suggesting that chronically elevated AMH induces anovulation,” he added. “We await, with great anticipation, future clinical studies to potentially further illustrate the apparent and intriguing role of AMH in the development of PCOS.”

This study was supported by the Queenie Victorina Neri Scholarship and a Research Grant from the American Society for Reproductive Medicine. One author reported financial relationships with Oviva Therapeutics; no other conflicts of interest were reported.

Editor’s note: This is the second in a two-part series commemorating the 100-year anniversary of the first use of insulin in humans. Part 1 of this series examined the rivalry behind the discovery and use of insulin.

One hundred years ago, teenager Leonard Thompson was the first patient with type 1 diabetes to be successfully treated with insulin, granting him a reprieve from what was a certain death sentence at the time.

Since then, research has gathered pace. In the century since insulin’s discovery and first use, recombinant DNA technology has allowed for the engineering of the insulin molecule, providing numerous short- and long-acting analog versions. At the same time, technological leaps in automated insulin delivery and monitoring of blood glucose ensure more time with glucose in range and fewer life-threatening complications for those with type 1 diabetes fortunate enough to have access to the technology. 

In spite of these advancements, there is still scope for further evolution of disease management, with the holy grail being the transplant of stem cell–derived islet cells capable of making insulin, ideally encased in some kind of protective device so that immunosuppression is not required.

Indeed, it is not unreasonable to “hope that type 1 diabetes will be a curable disease in the next 100 years,” said Elizabeth Stephens, MD, an endocrinologist who has type 1 diabetes and practices in Portland, Ore.
 

Type 1 diabetes: The past 100 years

The epidemiology of type 1 diabetes has shifted considerably since 1922. A century ago, given that average life expectancy in the United States was around 54 years, it was pretty much the only type of diabetes that doctors encountered. “There was some type 2 diabetes about in heavier people, but the focus was on type 1 diabetes,” noted Dr. Stephens.

Originally called juvenile diabetes because it was thought to only occur in children, “now 50% of people are diagnosed with type 1 diabetes ... over [the age of] 20,” explained Dr. Stephens.

In the United States, around 1.4 million adults 20 years and older, and 187,000 children younger than 20, have the disease, according to data from the National Diabetes Statistics Report 2020 by the Centers for Disease Control and Prevention. This total represents an increase of nearly 30% from 2017.

Over the years, theories as to the cause, or trigger, for type 1 diabetes “have included cow’s milk and [viral] infections,” said Dr. Stephens. “Most likely, there’s a genetic predisposition and some type of exposure, which creates the perfect storm to trigger disease.”

There are hints that COVID-19 might be precipitating type 1 diabetes in some people. Recently, the CDC found SARS-CoV-2 infection was associated with an increased risk for diabetes (all types) among youth, but not other acute respiratory infections. And two further studies from different parts of the world have recently identified an increase in the incidence of type 1 diabetes in children since the COVID-19 pandemic began, but the reasons remain unclear.

The global CoviDiab registry has also been established to collect data on patients with COVID-19–related diabetes.

The million-dollar question: Is COVID-19 itself is propagating type 1 diabetes or unmasking a predisposition to the disease sooner? The latter might be associated with a lower type 1 diabetes rate in the future, said Partha Kar, MBBS, OBE, national specialty advisor, diabetes, for National Health Service England.

“Right now, we don’t know the answer. Whichever way you look at it, it is likely there will be a rise in cases, and in countries where insulin is not freely available, healthcare systems need to have supply ready because insulin is lifesaving in type 1 diabetes,” Dr. Kar emphasized.
 

CGMs and automated insulin delivery: A ‘godsend’

A huge change has also been seen, most notably in the past 15 to 20 years, in the technological advancements that can help those with type 1 diabetes live an easier life.

Continuous glucose monitors (CGMs) and automated ways of delivering insulin, such as smart pens and insulin pumps, have made the daily life of a person with type 1 diabetes in the Western world considerably more comfortable.

CGMs provide a constant stream of data to an app, often wirelessly in sync with the insulin pump. However, on a global level, they are only available to a lucky few.

In England, pending National Institute for Health and Care Excellence) approval, any CGM should be available to all eligible patients with type 1 diabetes within the NHS from April 2022, Dr. Kar pointed out. In the United States, CGMs are often unaffordable and access is mostly dependent on a person’s health insurance.

Kersten Hall, PhD, a scientist and U.K.-based medical historian who recently wrote a book, “Insulin, the Crooked Timber” (Oxford, England: Oxford University Press, 2022) uncovering the lesser-known story behind the discovery of insulin, was diagnosed with adult-onset type 1 diabetes at the age of 41. Dr. Hall had always found the finger-prick blood glucose test to be a chore but now has a CGM. 

“It’s a total game changer for me: a godsend. I can’t sing its praises enough,” he said. “All it involves is the swipe of the phone and this provides a reading which tells me if my glucose is too low, so I eat something, or too high, so I might [go for] a run.”
 

Brewing insulin at scale

As described by Dr. Hall in his book, the journey from treating Mr. Thompson in 1922 to treating the masses began when biochemist James Collip, MD, PhD, discovered a means of purifying the animal pancreas extracts used to treat the teenager.

But production at scale presented a further challenge. This was overcome in 1924 when Eli Lilly drew on a technique used in the beer brewing process – where pH guides bitterness – to purify and manufacture large amounts of insulin.

By 1936, a range of slower-acting cattle and pig-derived insulins, the first produced by Novo Nordisk Pharmaceuticals, were developed.

However, it took 8,000 lb (approximately 3,600 kg) of pancreas glands from 23,500 animals to make 1 lb (0.5 kg) of insulin, so a more efficient process was badly needed.

Dr. Hall, who is a molecular biologist as well as an author, explains that the use of recombinant DNA technology to produce human insulin, as done by Genentech in the late 70s, was a key development in the story of modern insulin products. Genentech then provided synthetic human insulin for Eli Lilly to conduct clinical trials.

Human insulin most closely resembles porcine insulin structure and function, differing by only one amino acid, while human insulin differs from bovine insulin by three amino acid residues. This synthetic human insulin eliminated the allergies that the animal-derived products sometimes caused.

In the early 1980s, Eli Lilly produced Humulin, the first biosynthetic (made in Escherichia coli, hence the term, “bio”) human insulin.

This technology eventually “allowed for the alteration of specific amino acids in the sequence of the insulin protein to make insulin analogs [synthetic versions grown in E. coli and genetically altered for various properties] that act faster, or more slowly, than normal human insulin. By using the slow- and fast-acting insulins in combination, a patient can control their blood sugar levels with a much greater degree of finesse and precision,” Dr. Hall explained.

Today, a whole range of insulins are available, including ultra–rapid-acting, short-acting, intermediate-acting, long-acting, ultra–long-acting, and even inhaled insulin, although the latter is expensive, has been associated with side effects, and is less commonly used, according to Dr. Stephens.

Oral insulin formulations are even in the early stages of development, with candidate drugs by Generex and from the Oralis project.

“With insulin therapy, we try to reproduce the normal physiology of the healthy body and pancreas,” Dr. Stephens explained.

Insulin analogs are only made by three companies (Eli Lilly, Novo Nordisk, and Sanofi), and they are generally much more expensive than nonanalog human insulin. In the United Kingdom through the NHS, they cost twice as much.

In the United States today, one of the biggest barriers to proper care of type 1 diabetes is the cost of insulin, which can limit access. With the market controlled by these three large companies, the average cost of a unit of insulin in the United States, according to RAND research, was $98.17 in January 2021, compared with $7.52 in the United Kingdom and $12.00 in Canada. 

Several U.S. states have enacted legislation capping insulin copayments to at, or under, $100 a month. But the federal Build Back Better Framework Act – which would cap copayments for insulin at $35 – currently hangs in the balance.

Alongside these moves, in 2020 the Food and Drug Administration approved the first interchangeable biosimilar insulin for type 1 diabetes (and insulin-dependent type 2 diabetes) in children and adults, called Semglee (Mylan Pharmaceuticals). 

Biosimilars (essentially generic versions of branded insulins) are expected to be less expensive than branded analogs, but the indications so far are that they will only be around 20% cheaper.

“I totally fail to understand how the richest country in the world still has a debate about price caps, and we are looking at biosimilar markets to change the debate. This makes no sense to me at all,” stressed Dr. Kar. “For lifesaving drugs, they should be funded by the state.”

Insulin also remains unaffordable for many in numerous low- and middle-income countries, where most patients pay out-of-pocket for medicines. Globally, there are estimated to be around 30 million people who need insulin but cannot afford it.

How near to a cure in the coming decades?

Looking ahead to the coming years, if not the next 100, Dr. Stephens highlighted two important aspects of care.

First, the use of a CGM device in combination with an insulin pump (also known as a closed-loop system or artificial pancreas), where the CGM effectively tells the insulin pump how much insulin to automatically dispense, should revolutionize care.

A number of such closed-loop systems have recently been approved in both the United States, including systems from Medtronic and Omnipod, and Europe.

“I wear one of these and it’s been a life changer for me, but it doesn’t suit everyone because the technology can be cumbersome, but with time, hopefully things will become smaller and more accurate in insulin delivery,” Dr. Stephens added.

The second advance of interest is the development and transplantation of cells that produce insulin.

Dr. Stephens explained that someone living with type 1 diabetes has a lot to think about, not least, doing the math related to insulin requirement. “If we just had cells from a pancreas that could be transplanted and would do that for us, then it would be a total game changer.”

To date, Vertex Pharmaceuticals has successfully treated one patient – who had lived with type 1 diabetes for about 40 years and had recurrent episodes of severe hypoglycemia – with an infusion of stem cell–derived differentiated islet cells into his liver. The procedure resulted in near reversal of type 1 diabetes, with his insulin dose reduced from 34 to 3 units, and his hemoglobin A1c falling from 8.6% to 7.2%.

And although the patient, Brian Shelton, still needs to take immunosuppressive agents to prevent rejection of the stem cell–derived islets, “it’s a whole new life,” he recently told the New York Times.  

Another company called ViaCyte is also working on a similar approach.

Whether this is a cure for type 1 diabetes is still debatable, said Anne Peters, MD, of the University of Southern California, Los Angeles. “Is it true? In a word, no. But we are part of the way there, which is much closer than we were 6 months ago.”

There are also ongoing clinical trials of therapeutic interventions to prevent or delay the trajectory from presymptomatic to clinical type 1 diabetes. The most advanced is the anti-CD3 monoclonal antibody teplizumab (Tzield, Provention Bio), which was rejected by the FDA in July 2021, but has since been refiled. The company expects to hear from the agency by the end of March 2022 as to whether the resubmission has been accepted.
 

Diabetes specialist nurses/educators keep it human

Dr. Hall said he concurs with the late eminent U.K. diabetes specialist Robert Tattersall’s observation on what he considers one of the most important advances in the management and treatment of type 1 diabetes: the human touch.

Referring to Dr. Tattersall’s book, “Diabetes: A Biography,” Dr. Hall quoted: “If asked what innovation had made the most difference to their lives in the 1980s, patients with type 1 diabetes in England would unhesitatingly have chosen not human insulin, but the spread of diabetes specialist nurses ... these people (mainly women) did more in the last two decades of the 20th century to improve the standard of diabetes care than any other innovation or drug.”

In the United States, diabetes specialist nurses were called diabetes educators until recently, when the name changed to certified diabetes care and education specialist.

“Above all, they have humanized the service and given the patient a say in the otherwise unequal relationship with all-powerful doctors,” concluded Dr. Hall, again quoting Dr. Tattersall.

A version of this article first appeared on Medscape.com.

Editor’s note: This is the second in a two-part series commemorating the 100-year anniversary of the first use of insulin in humans. Part 1 of this series examined the rivalry behind the discovery and use of insulin.

One hundred years ago, teenager Leonard Thompson was the first patient with type 1 diabetes to be successfully treated with insulin, granting him a reprieve from what was a certain death sentence at the time.

Since then, research has gathered pace. In the century since insulin’s discovery and first use, recombinant DNA technology has allowed for the engineering of the insulin molecule, providing numerous short- and long-acting analog versions. At the same time, technological leaps in automated insulin delivery and monitoring of blood glucose ensure more time with glucose in range and fewer life-threatening complications for those with type 1 diabetes fortunate enough to have access to the technology. 

In spite of these advancements, there is still scope for further evolution of disease management, with the holy grail being the transplant of stem cell–derived islet cells capable of making insulin, ideally encased in some kind of protective device so that immunosuppression is not required.

Indeed, it is not unreasonable to “hope that type 1 diabetes will be a curable disease in the next 100 years,” said Elizabeth Stephens, MD, an endocrinologist who has type 1 diabetes and practices in Portland, Ore.
 

Type 1 diabetes: The past 100 years

The epidemiology of type 1 diabetes has shifted considerably since 1922. A century ago, given that average life expectancy in the United States was around 54 years, it was pretty much the only type of diabetes that doctors encountered. “There was some type 2 diabetes about in heavier people, but the focus was on type 1 diabetes,” noted Dr. Stephens.

Originally called juvenile diabetes because it was thought to only occur in children, “now 50% of people are diagnosed with type 1 diabetes ... over [the age of] 20,” explained Dr. Stephens.

In the United States, around 1.4 million adults 20 years and older, and 187,000 children younger than 20, have the disease, according to data from the National Diabetes Statistics Report 2020 by the Centers for Disease Control and Prevention. This total represents an increase of nearly 30% from 2017.

Over the years, theories as to the cause, or trigger, for type 1 diabetes “have included cow’s milk and [viral] infections,” said Dr. Stephens. “Most likely, there’s a genetic predisposition and some type of exposure, which creates the perfect storm to trigger disease.”

There are hints that COVID-19 might be precipitating type 1 diabetes in some people. Recently, the CDC found SARS-CoV-2 infection was associated with an increased risk for diabetes (all types) among youth, but not other acute respiratory infections. And two further studies from different parts of the world have recently identified an increase in the incidence of type 1 diabetes in children since the COVID-19 pandemic began, but the reasons remain unclear.

The global CoviDiab registry has also been established to collect data on patients with COVID-19–related diabetes.

The million-dollar question: Is COVID-19 itself is propagating type 1 diabetes or unmasking a predisposition to the disease sooner? The latter might be associated with a lower type 1 diabetes rate in the future, said Partha Kar, MBBS, OBE, national specialty advisor, diabetes, for National Health Service England.

“Right now, we don’t know the answer. Whichever way you look at it, it is likely there will be a rise in cases, and in countries where insulin is not freely available, healthcare systems need to have supply ready because insulin is lifesaving in type 1 diabetes,” Dr. Kar emphasized.
 

CGMs and automated insulin delivery: A ‘godsend’

A huge change has also been seen, most notably in the past 15 to 20 years, in the technological advancements that can help those with type 1 diabetes live an easier life.

Continuous glucose monitors (CGMs) and automated ways of delivering insulin, such as smart pens and insulin pumps, have made the daily life of a person with type 1 diabetes in the Western world considerably more comfortable.

CGMs provide a constant stream of data to an app, often wirelessly in sync with the insulin pump. However, on a global level, they are only available to a lucky few.

In England, pending National Institute for Health and Care Excellence) approval, any CGM should be available to all eligible patients with type 1 diabetes within the NHS from April 2022, Dr. Kar pointed out. In the United States, CGMs are often unaffordable and access is mostly dependent on a person’s health insurance.

Kersten Hall, PhD, a scientist and U.K.-based medical historian who recently wrote a book, “Insulin, the Crooked Timber” (Oxford, England: Oxford University Press, 2022) uncovering the lesser-known story behind the discovery of insulin, was diagnosed with adult-onset type 1 diabetes at the age of 41. Dr. Hall had always found the finger-prick blood glucose test to be a chore but now has a CGM. 

“It’s a total game changer for me: a godsend. I can’t sing its praises enough,” he said. “All it involves is the swipe of the phone and this provides a reading which tells me if my glucose is too low, so I eat something, or too high, so I might [go for] a run.”
 

Brewing insulin at scale

As described by Dr. Hall in his book, the journey from treating Mr. Thompson in 1922 to treating the masses began when biochemist James Collip, MD, PhD, discovered a means of purifying the animal pancreas extracts used to treat the teenager.

But production at scale presented a further challenge. This was overcome in 1924 when Eli Lilly drew on a technique used in the beer brewing process – where pH guides bitterness – to purify and manufacture large amounts of insulin.

By 1936, a range of slower-acting cattle and pig-derived insulins, the first produced by Novo Nordisk Pharmaceuticals, were developed.

However, it took 8,000 lb (approximately 3,600 kg) of pancreas glands from 23,500 animals to make 1 lb (0.5 kg) of insulin, so a more efficient process was badly needed.

Dr. Hall, who is a molecular biologist as well as an author, explains that the use of recombinant DNA technology to produce human insulin, as done by Genentech in the late 70s, was a key development in the story of modern insulin products. Genentech then provided synthetic human insulin for Eli Lilly to conduct clinical trials.

Human insulin most closely resembles porcine insulin structure and function, differing by only one amino acid, while human insulin differs from bovine insulin by three amino acid residues. This synthetic human insulin eliminated the allergies that the animal-derived products sometimes caused.

In the early 1980s, Eli Lilly produced Humulin, the first biosynthetic (made in Escherichia coli, hence the term, “bio”) human insulin.

This technology eventually “allowed for the alteration of specific amino acids in the sequence of the insulin protein to make insulin analogs [synthetic versions grown in E. coli and genetically altered for various properties] that act faster, or more slowly, than normal human insulin. By using the slow- and fast-acting insulins in combination, a patient can control their blood sugar levels with a much greater degree of finesse and precision,” Dr. Hall explained.

Today, a whole range of insulins are available, including ultra–rapid-acting, short-acting, intermediate-acting, long-acting, ultra–long-acting, and even inhaled insulin, although the latter is expensive, has been associated with side effects, and is less commonly used, according to Dr. Stephens.

Oral insulin formulations are even in the early stages of development, with candidate drugs by Generex and from the Oralis project.

“With insulin therapy, we try to reproduce the normal physiology of the healthy body and pancreas,” Dr. Stephens explained.

Insulin analogs are only made by three companies (Eli Lilly, Novo Nordisk, and Sanofi), and they are generally much more expensive than nonanalog human insulin. In the United Kingdom through the NHS, they cost twice as much.

In the United States today, one of the biggest barriers to proper care of type 1 diabetes is the cost of insulin, which can limit access. With the market controlled by these three large companies, the average cost of a unit of insulin in the United States, according to RAND research, was $98.17 in January 2021, compared with $7.52 in the United Kingdom and $12.00 in Canada. 

Several U.S. states have enacted legislation capping insulin copayments to at, or under, $100 a month. But the federal Build Back Better Framework Act – which would cap copayments for insulin at $35 – currently hangs in the balance.

Alongside these moves, in 2020 the Food and Drug Administration approved the first interchangeable biosimilar insulin for type 1 diabetes (and insulin-dependent type 2 diabetes) in children and adults, called Semglee (Mylan Pharmaceuticals). 

Biosimilars (essentially generic versions of branded insulins) are expected to be less expensive than branded analogs, but the indications so far are that they will only be around 20% cheaper.

“I totally fail to understand how the richest country in the world still has a debate about price caps, and we are looking at biosimilar markets to change the debate. This makes no sense to me at all,” stressed Dr. Kar. “For lifesaving drugs, they should be funded by the state.”

Insulin also remains unaffordable for many in numerous low- and middle-income countries, where most patients pay out-of-pocket for medicines. Globally, there are estimated to be around 30 million people who need insulin but cannot afford it.

How near to a cure in the coming decades?

Looking ahead to the coming years, if not the next 100, Dr. Stephens highlighted two important aspects of care.

First, the use of a CGM device in combination with an insulin pump (also known as a closed-loop system or artificial pancreas), where the CGM effectively tells the insulin pump how much insulin to automatically dispense, should revolutionize care.

A number of such closed-loop systems have recently been approved in both the United States, including systems from Medtronic and Omnipod, and Europe.

“I wear one of these and it’s been a life changer for me, but it doesn’t suit everyone because the technology can be cumbersome, but with time, hopefully things will become smaller and more accurate in insulin delivery,” Dr. Stephens added.

The second advance of interest is the development and transplantation of cells that produce insulin.

Dr. Stephens explained that someone living with type 1 diabetes has a lot to think about, not least, doing the math related to insulin requirement. “If we just had cells from a pancreas that could be transplanted and would do that for us, then it would be a total game changer.”

To date, Vertex Pharmaceuticals has successfully treated one patient – who had lived with type 1 diabetes for about 40 years and had recurrent episodes of severe hypoglycemia – with an infusion of stem cell–derived differentiated islet cells into his liver. The procedure resulted in near reversal of type 1 diabetes, with his insulin dose reduced from 34 to 3 units, and his hemoglobin A1c falling from 8.6% to 7.2%.

And although the patient, Brian Shelton, still needs to take immunosuppressive agents to prevent rejection of the stem cell–derived islets, “it’s a whole new life,” he recently told the New York Times.  

Another company called ViaCyte is also working on a similar approach.

Whether this is a cure for type 1 diabetes is still debatable, said Anne Peters, MD, of the University of Southern California, Los Angeles. “Is it true? In a word, no. But we are part of the way there, which is much closer than we were 6 months ago.”

There are also ongoing clinical trials of therapeutic interventions to prevent or delay the trajectory from presymptomatic to clinical type 1 diabetes. The most advanced is the anti-CD3 monoclonal antibody teplizumab (Tzield, Provention Bio), which was rejected by the FDA in July 2021, but has since been refiled. The company expects to hear from the agency by the end of March 2022 as to whether the resubmission has been accepted.
 

Diabetes specialist nurses/educators keep it human

Dr. Hall said he concurs with the late eminent U.K. diabetes specialist Robert Tattersall’s observation on what he considers one of the most important advances in the management and treatment of type 1 diabetes: the human touch.

Referring to Dr. Tattersall’s book, “Diabetes: A Biography,” Dr. Hall quoted: “If asked what innovation had made the most difference to their lives in the 1980s, patients with type 1 diabetes in England would unhesitatingly have chosen not human insulin, but the spread of diabetes specialist nurses ... these people (mainly women) did more in the last two decades of the 20th century to improve the standard of diabetes care than any other innovation or drug.”

In the United States, diabetes specialist nurses were called diabetes educators until recently, when the name changed to certified diabetes care and education specialist.

“Above all, they have humanized the service and given the patient a say in the otherwise unequal relationship with all-powerful doctors,” concluded Dr. Hall, again quoting Dr. Tattersall.

A version of this article first appeared on Medscape.com.

Editor’s note: This is the second in a two-part series commemorating the 100-year anniversary of the first use of insulin in humans. Part 1 of this series examined the rivalry behind the discovery and use of insulin.

One hundred years ago, teenager Leonard Thompson was the first patient with type 1 diabetes to be successfully treated with insulin, granting him a reprieve from what was a certain death sentence at the time.

Since then, research has gathered pace. In the century since insulin’s discovery and first use, recombinant DNA technology has allowed for the engineering of the insulin molecule, providing numerous short- and long-acting analog versions. At the same time, technological leaps in automated insulin delivery and monitoring of blood glucose ensure more time with glucose in range and fewer life-threatening complications for those with type 1 diabetes fortunate enough to have access to the technology. 

In spite of these advancements, there is still scope for further evolution of disease management, with the holy grail being the transplant of stem cell–derived islet cells capable of making insulin, ideally encased in some kind of protective device so that immunosuppression is not required.

Indeed, it is not unreasonable to “hope that type 1 diabetes will be a curable disease in the next 100 years,” said Elizabeth Stephens, MD, an endocrinologist who has type 1 diabetes and practices in Portland, Ore.
 

Type 1 diabetes: The past 100 years

The epidemiology of type 1 diabetes has shifted considerably since 1922. A century ago, given that average life expectancy in the United States was around 54 years, it was pretty much the only type of diabetes that doctors encountered. “There was some type 2 diabetes about in heavier people, but the focus was on type 1 diabetes,” noted Dr. Stephens.

Originally called juvenile diabetes because it was thought to only occur in children, “now 50% of people are diagnosed with type 1 diabetes ... over [the age of] 20,” explained Dr. Stephens.

In the United States, around 1.4 million adults 20 years and older, and 187,000 children younger than 20, have the disease, according to data from the National Diabetes Statistics Report 2020 by the Centers for Disease Control and Prevention. This total represents an increase of nearly 30% from 2017.

Over the years, theories as to the cause, or trigger, for type 1 diabetes “have included cow’s milk and [viral] infections,” said Dr. Stephens. “Most likely, there’s a genetic predisposition and some type of exposure, which creates the perfect storm to trigger disease.”

There are hints that COVID-19 might be precipitating type 1 diabetes in some people. Recently, the CDC found SARS-CoV-2 infection was associated with an increased risk for diabetes (all types) among youth, but not other acute respiratory infections. And two further studies from different parts of the world have recently identified an increase in the incidence of type 1 diabetes in children since the COVID-19 pandemic began, but the reasons remain unclear.

The global CoviDiab registry has also been established to collect data on patients with COVID-19–related diabetes.

The million-dollar question: Is COVID-19 itself is propagating type 1 diabetes or unmasking a predisposition to the disease sooner? The latter might be associated with a lower type 1 diabetes rate in the future, said Partha Kar, MBBS, OBE, national specialty advisor, diabetes, for National Health Service England.

“Right now, we don’t know the answer. Whichever way you look at it, it is likely there will be a rise in cases, and in countries where insulin is not freely available, healthcare systems need to have supply ready because insulin is lifesaving in type 1 diabetes,” Dr. Kar emphasized.
 

CGMs and automated insulin delivery: A ‘godsend’

A huge change has also been seen, most notably in the past 15 to 20 years, in the technological advancements that can help those with type 1 diabetes live an easier life.

Continuous glucose monitors (CGMs) and automated ways of delivering insulin, such as smart pens and insulin pumps, have made the daily life of a person with type 1 diabetes in the Western world considerably more comfortable.

CGMs provide a constant stream of data to an app, often wirelessly in sync with the insulin pump. However, on a global level, they are only available to a lucky few.

In England, pending National Institute for Health and Care Excellence) approval, any CGM should be available to all eligible patients with type 1 diabetes within the NHS from April 2022, Dr. Kar pointed out. In the United States, CGMs are often unaffordable and access is mostly dependent on a person’s health insurance.

Kersten Hall, PhD, a scientist and U.K.-based medical historian who recently wrote a book, “Insulin, the Crooked Timber” (Oxford, England: Oxford University Press, 2022) uncovering the lesser-known story behind the discovery of insulin, was diagnosed with adult-onset type 1 diabetes at the age of 41. Dr. Hall had always found the finger-prick blood glucose test to be a chore but now has a CGM. 

“It’s a total game changer for me: a godsend. I can’t sing its praises enough,” he said. “All it involves is the swipe of the phone and this provides a reading which tells me if my glucose is too low, so I eat something, or too high, so I might [go for] a run.”
 

Brewing insulin at scale

As described by Dr. Hall in his book, the journey from treating Mr. Thompson in 1922 to treating the masses began when biochemist James Collip, MD, PhD, discovered a means of purifying the animal pancreas extracts used to treat the teenager.

But production at scale presented a further challenge. This was overcome in 1924 when Eli Lilly drew on a technique used in the beer brewing process – where pH guides bitterness – to purify and manufacture large amounts of insulin.

By 1936, a range of slower-acting cattle and pig-derived insulins, the first produced by Novo Nordisk Pharmaceuticals, were developed.

However, it took 8,000 lb (approximately 3,600 kg) of pancreas glands from 23,500 animals to make 1 lb (0.5 kg) of insulin, so a more efficient process was badly needed.

Dr. Hall, who is a molecular biologist as well as an author, explains that the use of recombinant DNA technology to produce human insulin, as done by Genentech in the late 70s, was a key development in the story of modern insulin products. Genentech then provided synthetic human insulin for Eli Lilly to conduct clinical trials.

Human insulin most closely resembles porcine insulin structure and function, differing by only one amino acid, while human insulin differs from bovine insulin by three amino acid residues. This synthetic human insulin eliminated the allergies that the animal-derived products sometimes caused.

In the early 1980s, Eli Lilly produced Humulin, the first biosynthetic (made in Escherichia coli, hence the term, “bio”) human insulin.

This technology eventually “allowed for the alteration of specific amino acids in the sequence of the insulin protein to make insulin analogs [synthetic versions grown in E. coli and genetically altered for various properties] that act faster, or more slowly, than normal human insulin. By using the slow- and fast-acting insulins in combination, a patient can control their blood sugar levels with a much greater degree of finesse and precision,” Dr. Hall explained.

Today, a whole range of insulins are available, including ultra–rapid-acting, short-acting, intermediate-acting, long-acting, ultra–long-acting, and even inhaled insulin, although the latter is expensive, has been associated with side effects, and is less commonly used, according to Dr. Stephens.

Oral insulin formulations are even in the early stages of development, with candidate drugs by Generex and from the Oralis project.

“With insulin therapy, we try to reproduce the normal physiology of the healthy body and pancreas,” Dr. Stephens explained.

Insulin analogs are only made by three companies (Eli Lilly, Novo Nordisk, and Sanofi), and they are generally much more expensive than nonanalog human insulin. In the United Kingdom through the NHS, they cost twice as much.

In the United States today, one of the biggest barriers to proper care of type 1 diabetes is the cost of insulin, which can limit access. With the market controlled by these three large companies, the average cost of a unit of insulin in the United States, according to RAND research, was $98.17 in January 2021, compared with $7.52 in the United Kingdom and $12.00 in Canada. 

Several U.S. states have enacted legislation capping insulin copayments to at, or under, $100 a month. But the federal Build Back Better Framework Act – which would cap copayments for insulin at $35 – currently hangs in the balance.

Alongside these moves, in 2020 the Food and Drug Administration approved the first interchangeable biosimilar insulin for type 1 diabetes (and insulin-dependent type 2 diabetes) in children and adults, called Semglee (Mylan Pharmaceuticals). 

Biosimilars (essentially generic versions of branded insulins) are expected to be less expensive than branded analogs, but the indications so far are that they will only be around 20% cheaper.

“I totally fail to understand how the richest country in the world still has a debate about price caps, and we are looking at biosimilar markets to change the debate. This makes no sense to me at all,” stressed Dr. Kar. “For lifesaving drugs, they should be funded by the state.”

Insulin also remains unaffordable for many in numerous low- and middle-income countries, where most patients pay out-of-pocket for medicines. Globally, there are estimated to be around 30 million people who need insulin but cannot afford it.

How near to a cure in the coming decades?

Looking ahead to the coming years, if not the next 100, Dr. Stephens highlighted two important aspects of care.

First, the use of a CGM device in combination with an insulin pump (also known as a closed-loop system or artificial pancreas), where the CGM effectively tells the insulin pump how much insulin to automatically dispense, should revolutionize care.

A number of such closed-loop systems have recently been approved in both the United States, including systems from Medtronic and Omnipod, and Europe.

“I wear one of these and it’s been a life changer for me, but it doesn’t suit everyone because the technology can be cumbersome, but with time, hopefully things will become smaller and more accurate in insulin delivery,” Dr. Stephens added.

The second advance of interest is the development and transplantation of cells that produce insulin.

Dr. Stephens explained that someone living with type 1 diabetes has a lot to think about, not least, doing the math related to insulin requirement. “If we just had cells from a pancreas that could be transplanted and would do that for us, then it would be a total game changer.”

To date, Vertex Pharmaceuticals has successfully treated one patient – who had lived with type 1 diabetes for about 40 years and had recurrent episodes of severe hypoglycemia – with an infusion of stem cell–derived differentiated islet cells into his liver. The procedure resulted in near reversal of type 1 diabetes, with his insulin dose reduced from 34 to 3 units, and his hemoglobin A1c falling from 8.6% to 7.2%.

And although the patient, Brian Shelton, still needs to take immunosuppressive agents to prevent rejection of the stem cell–derived islets, “it’s a whole new life,” he recently told the New York Times.  

Another company called ViaCyte is also working on a similar approach.

Whether this is a cure for type 1 diabetes is still debatable, said Anne Peters, MD, of the University of Southern California, Los Angeles. “Is it true? In a word, no. But we are part of the way there, which is much closer than we were 6 months ago.”

There are also ongoing clinical trials of therapeutic interventions to prevent or delay the trajectory from presymptomatic to clinical type 1 diabetes. The most advanced is the anti-CD3 monoclonal antibody teplizumab (Tzield, Provention Bio), which was rejected by the FDA in July 2021, but has since been refiled. The company expects to hear from the agency by the end of March 2022 as to whether the resubmission has been accepted.
 

Diabetes specialist nurses/educators keep it human

Dr. Hall said he concurs with the late eminent U.K. diabetes specialist Robert Tattersall’s observation on what he considers one of the most important advances in the management and treatment of type 1 diabetes: the human touch.

Referring to Dr. Tattersall’s book, “Diabetes: A Biography,” Dr. Hall quoted: “If asked what innovation had made the most difference to their lives in the 1980s, patients with type 1 diabetes in England would unhesitatingly have chosen not human insulin, but the spread of diabetes specialist nurses ... these people (mainly women) did more in the last two decades of the 20th century to improve the standard of diabetes care than any other innovation or drug.”

In the United States, diabetes specialist nurses were called diabetes educators until recently, when the name changed to certified diabetes care and education specialist.

“Above all, they have humanized the service and given the patient a say in the otherwise unequal relationship with all-powerful doctors,” concluded Dr. Hall, again quoting Dr. Tattersall.

A version of this article first appeared on Medscape.com.

Sleeping with a light on can play havoc with insulin levels and consequently impair the response to glucose, a 2-night sleep-lab study of 20 people indicates.

“The most important finding” is that, compared with one night in a dim light environment, “one night of exposure to a moderate level of room light while sleeping with eyes closed increased heart rate and sympathetic [nervous system] activity during the entire sleep period,” said senior author Phyllis C. Zee, MD, PhD.

And on the morning following the moderate room light condition, a higher amount of insulin secretion was required to normalize glucose levels following ingestion of a bolus of glucose in an oral glucose tolerance test, consistent with higher insulin resistance, Dr. Zee, director of the center for circadian and sleep medicine at Northwestern University, Chicago, told this news organization in an email.

The study by Ivy C. Mason, PhD, also of Northwestern University, and colleagues was published March 14 in the Proceedings of the National Academy of Sciences.

Melatonin levels were similar under the two light conditions, Dr. Zee added, which “suggests that the effect of light during sleep on these cardiometabolic measures were more likely due to activation of the sympathetic [nervous] system and less likely due to changes in sleep or suppression of melatonin by light.”

“Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health,” the researchers conclude.

That means “turn lights off before sleeping,” Dr. Zee elaborated. If a light is needed for safety reasons, keep it as dim as possible, she advises, and avoid exposure to blue or green light, but instead try red-amber colors.
 

How light during sleep may affect insulin, melatonin, heart rate

Several studies have investigated the effect of light on sleep and metabolic outcomes, the researchers explain.

In one study, light in the bedroom was associated with obesity in women, and in another study, it was associated with risk of type 2 diabetes in an elderly population.

Research has suggested that nighttime light exposure may alter glucose metabolism by increasing insulin resistance; lowering melatonin levels, which alters insulin secretion; and having an arousing effect on the sympathetic autonomic nervous system (increasing the stress hormone cortisol or heart rate, and decreasing heart rate variability).

However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period has not been fully investigated.

The researchers enrolled and randomized 20 healthy young adults who were 18-40 years old and regularly went to sleep between 9 p.m. and 1 a.m. and slept 6.5-8.5 hours, to sleep 2 nights in the sleep laboratory under two conditions.

Ten participants (eight women, two men) slept in a dim light condition on night 1 and in a moderate light condition on night 2. The other 10 participants (six women, four men) slept 2 nights in the dim light condition.

The moderate light condition consisted of four 60-watt incandescent overhead ceiling light bulbs (a total of 100 lux), which “is bright enough to see, but not to read comfortably,” Dr. Zee explained. “It’s like hallway light in an apartment. But the people were sleeping, so about 90% of the light would be blocked by the eyelids.”

The dim light condition was less than 3 lux, which is dimmer than a night light.

When participants were awake, the room lighting was 240 lux.

Participants in each group were a mean age of 27 years and had a mean body mass index of 23 and 24 kg/m².

The week before the study, participants went to bed at 11 p.m. and slept for 7 hours (based on actigraphy measures). During the laboratory stay, the participants were allowed to sleep 8 hours, during which polysomnography was performed.  

They received standard meals at 2.5, 5, and 11 hours after waking and had 30 minutes to eat them. Snacking and caffeine were not permitted.

Participants were instructed to remain seated or standing in their room, but not exercise, when they were not sleeping. Blood samples to determine melatonin levels were collected hourly during wake and sleep via an intravenous line.

Participants slept for a similar time, around 7 hours, in both conditions.

Although melatonin levels were similar in both conditions, this was a relatively small sample, the researchers caution.

In the room light condition, participants spent proportionately more time in stage N2 sleep and less in slow-wave and rapid eye movement sleep. There was no increase in sleep fragmentation or arousals.

The research was partly supported by the Center for Circadian and Sleep Medicine at Northwestern University, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the American Heart Association. The researchers have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Sleeping with a light on can play havoc with insulin levels and consequently impair the response to glucose, a 2-night sleep-lab study of 20 people indicates.

“The most important finding” is that, compared with one night in a dim light environment, “one night of exposure to a moderate level of room light while sleeping with eyes closed increased heart rate and sympathetic [nervous system] activity during the entire sleep period,” said senior author Phyllis C. Zee, MD, PhD.

And on the morning following the moderate room light condition, a higher amount of insulin secretion was required to normalize glucose levels following ingestion of a bolus of glucose in an oral glucose tolerance test, consistent with higher insulin resistance, Dr. Zee, director of the center for circadian and sleep medicine at Northwestern University, Chicago, told this news organization in an email.

The study by Ivy C. Mason, PhD, also of Northwestern University, and colleagues was published March 14 in the Proceedings of the National Academy of Sciences.

Melatonin levels were similar under the two light conditions, Dr. Zee added, which “suggests that the effect of light during sleep on these cardiometabolic measures were more likely due to activation of the sympathetic [nervous] system and less likely due to changes in sleep or suppression of melatonin by light.”

“Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health,” the researchers conclude.

That means “turn lights off before sleeping,” Dr. Zee elaborated. If a light is needed for safety reasons, keep it as dim as possible, she advises, and avoid exposure to blue or green light, but instead try red-amber colors.
 

How light during sleep may affect insulin, melatonin, heart rate

Several studies have investigated the effect of light on sleep and metabolic outcomes, the researchers explain.

In one study, light in the bedroom was associated with obesity in women, and in another study, it was associated with risk of type 2 diabetes in an elderly population.

Research has suggested that nighttime light exposure may alter glucose metabolism by increasing insulin resistance; lowering melatonin levels, which alters insulin secretion; and having an arousing effect on the sympathetic autonomic nervous system (increasing the stress hormone cortisol or heart rate, and decreasing heart rate variability).

However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period has not been fully investigated.

The researchers enrolled and randomized 20 healthy young adults who were 18-40 years old and regularly went to sleep between 9 p.m. and 1 a.m. and slept 6.5-8.5 hours, to sleep 2 nights in the sleep laboratory under two conditions.

Ten participants (eight women, two men) slept in a dim light condition on night 1 and in a moderate light condition on night 2. The other 10 participants (six women, four men) slept 2 nights in the dim light condition.

The moderate light condition consisted of four 60-watt incandescent overhead ceiling light bulbs (a total of 100 lux), which “is bright enough to see, but not to read comfortably,” Dr. Zee explained. “It’s like hallway light in an apartment. But the people were sleeping, so about 90% of the light would be blocked by the eyelids.”

The dim light condition was less than 3 lux, which is dimmer than a night light.

When participants were awake, the room lighting was 240 lux.

Participants in each group were a mean age of 27 years and had a mean body mass index of 23 and 24 kg/m².

The week before the study, participants went to bed at 11 p.m. and slept for 7 hours (based on actigraphy measures). During the laboratory stay, the participants were allowed to sleep 8 hours, during which polysomnography was performed.  

They received standard meals at 2.5, 5, and 11 hours after waking and had 30 minutes to eat them. Snacking and caffeine were not permitted.

Participants were instructed to remain seated or standing in their room, but not exercise, when they were not sleeping. Blood samples to determine melatonin levels were collected hourly during wake and sleep via an intravenous line.

Participants slept for a similar time, around 7 hours, in both conditions.

Although melatonin levels were similar in both conditions, this was a relatively small sample, the researchers caution.

In the room light condition, participants spent proportionately more time in stage N2 sleep and less in slow-wave and rapid eye movement sleep. There was no increase in sleep fragmentation or arousals.

The research was partly supported by the Center for Circadian and Sleep Medicine at Northwestern University, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the American Heart Association. The researchers have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Sleeping with a light on can play havoc with insulin levels and consequently impair the response to glucose, a 2-night sleep-lab study of 20 people indicates.

“The most important finding” is that, compared with one night in a dim light environment, “one night of exposure to a moderate level of room light while sleeping with eyes closed increased heart rate and sympathetic [nervous system] activity during the entire sleep period,” said senior author Phyllis C. Zee, MD, PhD.

And on the morning following the moderate room light condition, a higher amount of insulin secretion was required to normalize glucose levels following ingestion of a bolus of glucose in an oral glucose tolerance test, consistent with higher insulin resistance, Dr. Zee, director of the center for circadian and sleep medicine at Northwestern University, Chicago, told this news organization in an email.

The study by Ivy C. Mason, PhD, also of Northwestern University, and colleagues was published March 14 in the Proceedings of the National Academy of Sciences.

Melatonin levels were similar under the two light conditions, Dr. Zee added, which “suggests that the effect of light during sleep on these cardiometabolic measures were more likely due to activation of the sympathetic [nervous] system and less likely due to changes in sleep or suppression of melatonin by light.”

“Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health,” the researchers conclude.

That means “turn lights off before sleeping,” Dr. Zee elaborated. If a light is needed for safety reasons, keep it as dim as possible, she advises, and avoid exposure to blue or green light, but instead try red-amber colors.
 

How light during sleep may affect insulin, melatonin, heart rate

Several studies have investigated the effect of light on sleep and metabolic outcomes, the researchers explain.

In one study, light in the bedroom was associated with obesity in women, and in another study, it was associated with risk of type 2 diabetes in an elderly population.

Research has suggested that nighttime light exposure may alter glucose metabolism by increasing insulin resistance; lowering melatonin levels, which alters insulin secretion; and having an arousing effect on the sympathetic autonomic nervous system (increasing the stress hormone cortisol or heart rate, and decreasing heart rate variability).

However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period has not been fully investigated.

The researchers enrolled and randomized 20 healthy young adults who were 18-40 years old and regularly went to sleep between 9 p.m. and 1 a.m. and slept 6.5-8.5 hours, to sleep 2 nights in the sleep laboratory under two conditions.

Ten participants (eight women, two men) slept in a dim light condition on night 1 and in a moderate light condition on night 2. The other 10 participants (six women, four men) slept 2 nights in the dim light condition.

The moderate light condition consisted of four 60-watt incandescent overhead ceiling light bulbs (a total of 100 lux), which “is bright enough to see, but not to read comfortably,” Dr. Zee explained. “It’s like hallway light in an apartment. But the people were sleeping, so about 90% of the light would be blocked by the eyelids.”

The dim light condition was less than 3 lux, which is dimmer than a night light.

When participants were awake, the room lighting was 240 lux.

Participants in each group were a mean age of 27 years and had a mean body mass index of 23 and 24 kg/m².

The week before the study, participants went to bed at 11 p.m. and slept for 7 hours (based on actigraphy measures). During the laboratory stay, the participants were allowed to sleep 8 hours, during which polysomnography was performed.  

They received standard meals at 2.5, 5, and 11 hours after waking and had 30 minutes to eat them. Snacking and caffeine were not permitted.

Participants were instructed to remain seated or standing in their room, but not exercise, when they were not sleeping. Blood samples to determine melatonin levels were collected hourly during wake and sleep via an intravenous line.

Participants slept for a similar time, around 7 hours, in both conditions.

Although melatonin levels were similar in both conditions, this was a relatively small sample, the researchers caution.

In the room light condition, participants spent proportionately more time in stage N2 sleep and less in slow-wave and rapid eye movement sleep. There was no increase in sleep fragmentation or arousals.

The research was partly supported by the Center for Circadian and Sleep Medicine at Northwestern University, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the American Heart Association. The researchers have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

International experts have created recommendations on ways to improve adherence to statin therapy by offering doctors guidance on how to distinguish between true side effects of statins and those arising due to patients’ expectations of side effects.

A position paper from the International Lipid Expert Panel (ILEP), a group of over 70 experts worldwide, provides a step-by-step approach to diagnosing and managing symptoms, such as muscle aches, and encourages patients to continue the statin therapy they have been prescribed.

The authors described in their paper, published in the Journal of Cachexia, Sarcopenia, and Muscle, how statins are among the most commonly prescribed drugs globally, with “strong and unambiguous evidence” that statin treatment makes a significant difference in preventing cardiovascular disease and dying from it.

They said how, although a recent meta-analysis showed the prevalence of statin intolerance is less than 10%, “as many as 1 in 2 patients stop taking statins, reduce the dose, or take them irregularly because they believe they are responsible for side effects.”

In addition to misattribution of aches and pains, a substantial proportion of statin-associated muscle symptoms (SAMS) result from the action of taking medicines and the expectation that medicines cause side effects. A systematic review of trials estimated that between 38% and 78% of SAMS-related statin intolerance could be attributed to expectation alone.
 

Nocebo/drucebo effect

President of the ILEP, Professor Maciej Banach, of the Medical University of Lodz and the University of Zielona Góra, both in Poland, who originated these recommendations, said: “There is an enormous worldwide problem with diagnosing statin intolerance correctly. In addition, we know that most diagnosed statin side effects should not, in fact, be attributed to statin therapy.”

He highlighted how as much as 70% of statin side effect symptoms may be due to a psychological phenomenon called the “nocebo” or “drucebo” effect.

“The ‘nocebo/drucebo’ effect is when patients’ expectations that they will experience side effects from the statins result in them actually experiencing these symptoms,” Professor Banach explained. Knowledge gained from the internet, leaflets, friends and family, and other sources, for example, about the most common side effects – muscle pain and liver complaints – can “result in them discontinuing their therapy and, therefore, increasing their risk of heart problems, stroke, and death,” he cautioned.

First author of the paper, Dr. Peter Penson, a reader in Cardiovascular Pharmacology at Liverpool John Moores University, England, said “the benefits of statins are not seen immediately by patients, whilst the associated adverse effects are more tangible, and so many patients stop taking statins, thereby putting themselves at risk of serious illness or death.”
 

A practical evidence-based guide

The authors expressed hope that their recommendations would help doctors improve patient-centered care for those patients at risk of cardiovascular disease and help these patients understand the reason for their treatment, the benefits, including that statins may prolong their lives, and the potential harms, thus enabling the patient to “make a fully informed decision about commencing and continuing therapy.”

The recommendations include:

• That health care professionals should consider the nocebo/drucebo effect when they first prescribe statins and provide information to patients about the rationale and benefits of the therapy
• The Personalized Lipid Intervention Plan (PLIP) should be used to help this process. It estimates the patient’s 10-year risk of cardiovascular disease with and without statin therapy, as well as providing clear information on adverse side effects, including that muscle symptoms are common but rarely caused by statins
• How to effectively diagnose statin intolerance and exclude nocebo/drucebo effect
• Routine follow-up to check the safety and efficacy of the therapy is recommended, and strategies for managing patients with complete statin intolerance are provided, within the recommendations. Also offered is advice about improving adherence to statin therapy and suggestions for the identification and management of the “relatively small number of patients who have true statin intolerance.”

Dr. Penson emphasized how this was the first paper to deal explicitly with the nocebo/drucebo effect and offers “practical and evidence-based suggestions” to help support individuals who are at risk of cardiovascular disease but who experience adverse effects attributable to their medicines. He added how the PLIP summarizes important lifestyle advice to help patients reduce their risk of heart attacks and strokes and also discusses the evidence for non-statin drugs that can be used to lower cholesterol.

Dr. Penson pointed out how “the vast majority of patients can take statins safely and that the benefits greatly outweigh the potential risk of side effects” and, therefore, an individual’s risk of heart problems, stroke, and death, can be reduced.

A version of this article first appeared on Medscape.com.

International experts have created recommendations on ways to improve adherence to statin therapy by offering doctors guidance on how to distinguish between true side effects of statins and those arising due to patients’ expectations of side effects.

A position paper from the International Lipid Expert Panel (ILEP), a group of over 70 experts worldwide, provides a step-by-step approach to diagnosing and managing symptoms, such as muscle aches, and encourages patients to continue the statin therapy they have been prescribed.

The authors described in their paper, published in the Journal of Cachexia, Sarcopenia, and Muscle, how statins are among the most commonly prescribed drugs globally, with “strong and unambiguous evidence” that statin treatment makes a significant difference in preventing cardiovascular disease and dying from it.

They said how, although a recent meta-analysis showed the prevalence of statin intolerance is less than 10%, “as many as 1 in 2 patients stop taking statins, reduce the dose, or take them irregularly because they believe they are responsible for side effects.”

In addition to misattribution of aches and pains, a substantial proportion of statin-associated muscle symptoms (SAMS) result from the action of taking medicines and the expectation that medicines cause side effects. A systematic review of trials estimated that between 38% and 78% of SAMS-related statin intolerance could be attributed to expectation alone.
 

Nocebo/drucebo effect

President of the ILEP, Professor Maciej Banach, of the Medical University of Lodz and the University of Zielona Góra, both in Poland, who originated these recommendations, said: “There is an enormous worldwide problem with diagnosing statin intolerance correctly. In addition, we know that most diagnosed statin side effects should not, in fact, be attributed to statin therapy.”

He highlighted how as much as 70% of statin side effect symptoms may be due to a psychological phenomenon called the “nocebo” or “drucebo” effect.

“The ‘nocebo/drucebo’ effect is when patients’ expectations that they will experience side effects from the statins result in them actually experiencing these symptoms,” Professor Banach explained. Knowledge gained from the internet, leaflets, friends and family, and other sources, for example, about the most common side effects – muscle pain and liver complaints – can “result in them discontinuing their therapy and, therefore, increasing their risk of heart problems, stroke, and death,” he cautioned.

First author of the paper, Dr. Peter Penson, a reader in Cardiovascular Pharmacology at Liverpool John Moores University, England, said “the benefits of statins are not seen immediately by patients, whilst the associated adverse effects are more tangible, and so many patients stop taking statins, thereby putting themselves at risk of serious illness or death.”
 

A practical evidence-based guide

The authors expressed hope that their recommendations would help doctors improve patient-centered care for those patients at risk of cardiovascular disease and help these patients understand the reason for their treatment, the benefits, including that statins may prolong their lives, and the potential harms, thus enabling the patient to “make a fully informed decision about commencing and continuing therapy.”

The recommendations include:

• That health care professionals should consider the nocebo/drucebo effect when they first prescribe statins and provide information to patients about the rationale and benefits of the therapy
• The Personalized Lipid Intervention Plan (PLIP) should be used to help this process. It estimates the patient’s 10-year risk of cardiovascular disease with and without statin therapy, as well as providing clear information on adverse side effects, including that muscle symptoms are common but rarely caused by statins
• How to effectively diagnose statin intolerance and exclude nocebo/drucebo effect
• Routine follow-up to check the safety and efficacy of the therapy is recommended, and strategies for managing patients with complete statin intolerance are provided, within the recommendations. Also offered is advice about improving adherence to statin therapy and suggestions for the identification and management of the “relatively small number of patients who have true statin intolerance.”

Dr. Penson emphasized how this was the first paper to deal explicitly with the nocebo/drucebo effect and offers “practical and evidence-based suggestions” to help support individuals who are at risk of cardiovascular disease but who experience adverse effects attributable to their medicines. He added how the PLIP summarizes important lifestyle advice to help patients reduce their risk of heart attacks and strokes and also discusses the evidence for non-statin drugs that can be used to lower cholesterol.

Dr. Penson pointed out how “the vast majority of patients can take statins safely and that the benefits greatly outweigh the potential risk of side effects” and, therefore, an individual’s risk of heart problems, stroke, and death, can be reduced.

A version of this article first appeared on Medscape.com.

International experts have created recommendations on ways to improve adherence to statin therapy by offering doctors guidance on how to distinguish between true side effects of statins and those arising due to patients’ expectations of side effects.

A position paper from the International Lipid Expert Panel (ILEP), a group of over 70 experts worldwide, provides a step-by-step approach to diagnosing and managing symptoms, such as muscle aches, and encourages patients to continue the statin therapy they have been prescribed.

The authors described in their paper, published in the Journal of Cachexia, Sarcopenia, and Muscle, how statins are among the most commonly prescribed drugs globally, with “strong and unambiguous evidence” that statin treatment makes a significant difference in preventing cardiovascular disease and dying from it.

They said how, although a recent meta-analysis showed the prevalence of statin intolerance is less than 10%, “as many as 1 in 2 patients stop taking statins, reduce the dose, or take them irregularly because they believe they are responsible for side effects.”

In addition to misattribution of aches and pains, a substantial proportion of statin-associated muscle symptoms (SAMS) result from the action of taking medicines and the expectation that medicines cause side effects. A systematic review of trials estimated that between 38% and 78% of SAMS-related statin intolerance could be attributed to expectation alone.
 

Nocebo/drucebo effect

President of the ILEP, Professor Maciej Banach, of the Medical University of Lodz and the University of Zielona Góra, both in Poland, who originated these recommendations, said: “There is an enormous worldwide problem with diagnosing statin intolerance correctly. In addition, we know that most diagnosed statin side effects should not, in fact, be attributed to statin therapy.”

He highlighted how as much as 70% of statin side effect symptoms may be due to a psychological phenomenon called the “nocebo” or “drucebo” effect.

“The ‘nocebo/drucebo’ effect is when patients’ expectations that they will experience side effects from the statins result in them actually experiencing these symptoms,” Professor Banach explained. Knowledge gained from the internet, leaflets, friends and family, and other sources, for example, about the most common side effects – muscle pain and liver complaints – can “result in them discontinuing their therapy and, therefore, increasing their risk of heart problems, stroke, and death,” he cautioned.

First author of the paper, Dr. Peter Penson, a reader in Cardiovascular Pharmacology at Liverpool John Moores University, England, said “the benefits of statins are not seen immediately by patients, whilst the associated adverse effects are more tangible, and so many patients stop taking statins, thereby putting themselves at risk of serious illness or death.”
 

A practical evidence-based guide

The authors expressed hope that their recommendations would help doctors improve patient-centered care for those patients at risk of cardiovascular disease and help these patients understand the reason for their treatment, the benefits, including that statins may prolong their lives, and the potential harms, thus enabling the patient to “make a fully informed decision about commencing and continuing therapy.”

The recommendations include:

• That health care professionals should consider the nocebo/drucebo effect when they first prescribe statins and provide information to patients about the rationale and benefits of the therapy
• The Personalized Lipid Intervention Plan (PLIP) should be used to help this process. It estimates the patient’s 10-year risk of cardiovascular disease with and without statin therapy, as well as providing clear information on adverse side effects, including that muscle symptoms are common but rarely caused by statins
• How to effectively diagnose statin intolerance and exclude nocebo/drucebo effect
• Routine follow-up to check the safety and efficacy of the therapy is recommended, and strategies for managing patients with complete statin intolerance are provided, within the recommendations. Also offered is advice about improving adherence to statin therapy and suggestions for the identification and management of the “relatively small number of patients who have true statin intolerance.”

Dr. Penson emphasized how this was the first paper to deal explicitly with the nocebo/drucebo effect and offers “practical and evidence-based suggestions” to help support individuals who are at risk of cardiovascular disease but who experience adverse effects attributable to their medicines. He added how the PLIP summarizes important lifestyle advice to help patients reduce their risk of heart attacks and strokes and also discusses the evidence for non-statin drugs that can be used to lower cholesterol.

Dr. Penson pointed out how “the vast majority of patients can take statins safely and that the benefits greatly outweigh the potential risk of side effects” and, therefore, an individual’s risk of heart problems, stroke, and death, can be reduced.

A version of this article first appeared on Medscape.com.

A new report shows considerable gaps in the awareness, treatment, and control of hypertension in premenopausal women in the United States, with a key driver being regular access to health care.

In a nationally representative sample of women ages 35-54 with no prior cardiovascular disease, the prevalence of hypertension increased 8% from an estimated 15.2 million women between 2011 and 2014 to 16.4 million women between 2015 and 2018.

What’s more, the percentage of women with controlled hypertension dropped over the two time periods from 55% to 50%, which is well below the government’s Million Hearts target of 70%.

Missed opportunities for hypertension control in these premenopausal women were a lack of awareness of their hypertension in 23%, ineffective treatment in 34%, and a lack of health care access in 43%; increasing to 51% in non-Hispanic Black patients and 56% in Hispanic patients.

Notably, lack of health care access affected an estimated 3.1 million women (45%) in 2011-2014 and 3.5 million women (43%) in 2015-2018.

Equally stubborn over the two time periods was the lack of effective treatment, affecting 2.1 million (31%) versus 2.8 million (34%) women, and lack of awareness, affecting 1.6 million (24%) versus 1.9 million (23%) women.

“There’s been no improvement over the past decade, and there is evidence of race/ethnic disparities,” study author Susan Hennessy, PhD, said at the recent Epidemiology, Prevention/Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference sponsored by the American Heart Association.

The prevalence of uncontrolled hypertension among non-Hispanic Whites was less than that of the U.S. population, at 44%, and most of the missed opportunities were due to uncontrolled blood pressure (BP), noted Dr. Hennessy, a researcher with the University of California, San Francisco School of Medicine.

However, the uncontrolled prevalence was 54% in non-Hispanic Black women and 66% in Hispanic women. “In both of these subgroups, over half of the missed opportunities occur because these women have no regular access to health care,” she said.

In women who identified as “other,” which includes non-Hispanic Asian and mixed-race populations, the uncontrolled prevalence reached 70%, and the biggest missed opportunity was in those who were untreated.

Raising awareness, empowering women, and delivery of guideline-concordant care will help premenopausal women gain control of their blood pressure, Dr. Hennessy said. “But underpinning all of this is ensuring equitable health care access, because if we fail to get women into the system, then we have no opportunity to help them lower their blood pressure.”

She reminded the audience that cardiovascular disease (CVD) is the number one killer of women in the United States and that CVD risk, mediated through hypertension, increases after menopause. Thus, managing hypertension prior to this life event is an important element of primary prevention of CVD and should be a priority.

Session moderator Sadiya S. Khan, MD, Northwestern University Feinberg School of Medicine, Chicago, told this news organization that the findings should raise “alarm and concern that hypertension is not just a disease of the old but very prevalent in younger women, particularly around the time of pregnancy. And this is a clear driver of maternal morbidity and mortality as well.”

“This idea that patients should ‘Know Your Numbers’ is really important, and we talk a lot about that for hypertension, but if you don’t have a doctor, if you don’t have someone to go to, it’s very hard to know or understand what your numbers mean,” she said. “I think that’s really the main message.”

Speaking to this news organization, Dr. Hennessy said there’s no simple solution to the problem, given that some women are not even in the system, whereas others are not being treated effectively, but that increasing opportunities to screen BP would be a start. That could be through community programs, similar to the Barbershop Hypertension trial, or by making BP devices available for home monitoring.

“Again, this is about empowering ourselves to take some level of control, but, as a system, we have to be able to make it equitable for everyone and make sure they have the right equipment, the right cuff size,” she said. “The disparities arise because of the social determinants of health, so if these women are struggling to put food on the table, they aren’t going to be able to afford a blood pressure cuff.”

During a discussion of the findings, audience members noted that the National Health and Nutrition Examination Survey (NHANES) data used for the analysis were somewhat dated. Dr. Hennessy also pointed out that NHANES blood pressure is measured up to three times during a single visit, which differs from clinical practice, and that responses were based on self-report and thus subject to recall bias.

The sample included 3,343 women aged 35-54 years with no prior cardiovascular disease, representing an estimated 31.6 million American women. Hypertension was defined by a systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg or current BP medication use.

The authors and Dr. Khan report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new report shows considerable gaps in the awareness, treatment, and control of hypertension in premenopausal women in the United States, with a key driver being regular access to health care.

In a nationally representative sample of women ages 35-54 with no prior cardiovascular disease, the prevalence of hypertension increased 8% from an estimated 15.2 million women between 2011 and 2014 to 16.4 million women between 2015 and 2018.

What’s more, the percentage of women with controlled hypertension dropped over the two time periods from 55% to 50%, which is well below the government’s Million Hearts target of 70%.

Missed opportunities for hypertension control in these premenopausal women were a lack of awareness of their hypertension in 23%, ineffective treatment in 34%, and a lack of health care access in 43%; increasing to 51% in non-Hispanic Black patients and 56% in Hispanic patients.

Notably, lack of health care access affected an estimated 3.1 million women (45%) in 2011-2014 and 3.5 million women (43%) in 2015-2018.

Equally stubborn over the two time periods was the lack of effective treatment, affecting 2.1 million (31%) versus 2.8 million (34%) women, and lack of awareness, affecting 1.6 million (24%) versus 1.9 million (23%) women.

“There’s been no improvement over the past decade, and there is evidence of race/ethnic disparities,” study author Susan Hennessy, PhD, said at the recent Epidemiology, Prevention/Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference sponsored by the American Heart Association.

The prevalence of uncontrolled hypertension among non-Hispanic Whites was less than that of the U.S. population, at 44%, and most of the missed opportunities were due to uncontrolled blood pressure (BP), noted Dr. Hennessy, a researcher with the University of California, San Francisco School of Medicine.

However, the uncontrolled prevalence was 54% in non-Hispanic Black women and 66% in Hispanic women. “In both of these subgroups, over half of the missed opportunities occur because these women have no regular access to health care,” she said.

In women who identified as “other,” which includes non-Hispanic Asian and mixed-race populations, the uncontrolled prevalence reached 70%, and the biggest missed opportunity was in those who were untreated.

Raising awareness, empowering women, and delivery of guideline-concordant care will help premenopausal women gain control of their blood pressure, Dr. Hennessy said. “But underpinning all of this is ensuring equitable health care access, because if we fail to get women into the system, then we have no opportunity to help them lower their blood pressure.”

She reminded the audience that cardiovascular disease (CVD) is the number one killer of women in the United States and that CVD risk, mediated through hypertension, increases after menopause. Thus, managing hypertension prior to this life event is an important element of primary prevention of CVD and should be a priority.

Session moderator Sadiya S. Khan, MD, Northwestern University Feinberg School of Medicine, Chicago, told this news organization that the findings should raise “alarm and concern that hypertension is not just a disease of the old but very prevalent in younger women, particularly around the time of pregnancy. And this is a clear driver of maternal morbidity and mortality as well.”

“This idea that patients should ‘Know Your Numbers’ is really important, and we talk a lot about that for hypertension, but if you don’t have a doctor, if you don’t have someone to go to, it’s very hard to know or understand what your numbers mean,” she said. “I think that’s really the main message.”

Speaking to this news organization, Dr. Hennessy said there’s no simple solution to the problem, given that some women are not even in the system, whereas others are not being treated effectively, but that increasing opportunities to screen BP would be a start. That could be through community programs, similar to the Barbershop Hypertension trial, or by making BP devices available for home monitoring.

“Again, this is about empowering ourselves to take some level of control, but, as a system, we have to be able to make it equitable for everyone and make sure they have the right equipment, the right cuff size,” she said. “The disparities arise because of the social determinants of health, so if these women are struggling to put food on the table, they aren’t going to be able to afford a blood pressure cuff.”

During a discussion of the findings, audience members noted that the National Health and Nutrition Examination Survey (NHANES) data used for the analysis were somewhat dated. Dr. Hennessy also pointed out that NHANES blood pressure is measured up to three times during a single visit, which differs from clinical practice, and that responses were based on self-report and thus subject to recall bias.

The sample included 3,343 women aged 35-54 years with no prior cardiovascular disease, representing an estimated 31.6 million American women. Hypertension was defined by a systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg or current BP medication use.

The authors and Dr. Khan report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new report shows considerable gaps in the awareness, treatment, and control of hypertension in premenopausal women in the United States, with a key driver being regular access to health care.

In a nationally representative sample of women ages 35-54 with no prior cardiovascular disease, the prevalence of hypertension increased 8% from an estimated 15.2 million women between 2011 and 2014 to 16.4 million women between 2015 and 2018.

What’s more, the percentage of women with controlled hypertension dropped over the two time periods from 55% to 50%, which is well below the government’s Million Hearts target of 70%.

Missed opportunities for hypertension control in these premenopausal women were a lack of awareness of their hypertension in 23%, ineffective treatment in 34%, and a lack of health care access in 43%; increasing to 51% in non-Hispanic Black patients and 56% in Hispanic patients.

Notably, lack of health care access affected an estimated 3.1 million women (45%) in 2011-2014 and 3.5 million women (43%) in 2015-2018.

Equally stubborn over the two time periods was the lack of effective treatment, affecting 2.1 million (31%) versus 2.8 million (34%) women, and lack of awareness, affecting 1.6 million (24%) versus 1.9 million (23%) women.

“There’s been no improvement over the past decade, and there is evidence of race/ethnic disparities,” study author Susan Hennessy, PhD, said at the recent Epidemiology, Prevention/Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference sponsored by the American Heart Association.

The prevalence of uncontrolled hypertension among non-Hispanic Whites was less than that of the U.S. population, at 44%, and most of the missed opportunities were due to uncontrolled blood pressure (BP), noted Dr. Hennessy, a researcher with the University of California, San Francisco School of Medicine.

However, the uncontrolled prevalence was 54% in non-Hispanic Black women and 66% in Hispanic women. “In both of these subgroups, over half of the missed opportunities occur because these women have no regular access to health care,” she said.

In women who identified as “other,” which includes non-Hispanic Asian and mixed-race populations, the uncontrolled prevalence reached 70%, and the biggest missed opportunity was in those who were untreated.

Raising awareness, empowering women, and delivery of guideline-concordant care will help premenopausal women gain control of their blood pressure, Dr. Hennessy said. “But underpinning all of this is ensuring equitable health care access, because if we fail to get women into the system, then we have no opportunity to help them lower their blood pressure.”

She reminded the audience that cardiovascular disease (CVD) is the number one killer of women in the United States and that CVD risk, mediated through hypertension, increases after menopause. Thus, managing hypertension prior to this life event is an important element of primary prevention of CVD and should be a priority.

Session moderator Sadiya S. Khan, MD, Northwestern University Feinberg School of Medicine, Chicago, told this news organization that the findings should raise “alarm and concern that hypertension is not just a disease of the old but very prevalent in younger women, particularly around the time of pregnancy. And this is a clear driver of maternal morbidity and mortality as well.”

“This idea that patients should ‘Know Your Numbers’ is really important, and we talk a lot about that for hypertension, but if you don’t have a doctor, if you don’t have someone to go to, it’s very hard to know or understand what your numbers mean,” she said. “I think that’s really the main message.”

Speaking to this news organization, Dr. Hennessy said there’s no simple solution to the problem, given that some women are not even in the system, whereas others are not being treated effectively, but that increasing opportunities to screen BP would be a start. That could be through community programs, similar to the Barbershop Hypertension trial, or by making BP devices available for home monitoring.

“Again, this is about empowering ourselves to take some level of control, but, as a system, we have to be able to make it equitable for everyone and make sure they have the right equipment, the right cuff size,” she said. “The disparities arise because of the social determinants of health, so if these women are struggling to put food on the table, they aren’t going to be able to afford a blood pressure cuff.”

During a discussion of the findings, audience members noted that the National Health and Nutrition Examination Survey (NHANES) data used for the analysis were somewhat dated. Dr. Hennessy also pointed out that NHANES blood pressure is measured up to three times during a single visit, which differs from clinical practice, and that responses were based on self-report and thus subject to recall bias.

The sample included 3,343 women aged 35-54 years with no prior cardiovascular disease, representing an estimated 31.6 million American women. Hypertension was defined by a systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg or current BP medication use.

The authors and Dr. Khan report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

As public attention continues to focus on making insulin affordable, a new online guide is available to help clinicians approach discussions with patients about diabetes medication affordability and access.

The resource, “Having Healthcare Cost Conversations to Improve Patient Outcomes: A Practical Guide,” was jointly developed by the Association of Diabetes Care & Education Specialists and Beyond Type 1, the nonprofit patient advocacy organization.

Indeed, the guide appeared as President Biden discussed his proposal to cap insulin costs at $35 per insulin vial during the State of the Union address, during which he introduced a young boy with type 1 diabetes in the guest box, as reported by this news organization. On March 3, Civica, a nonprofit coalition of health systems and philanthropies, announced it plans to manufacture generic insulin at a deeply discounted price, as reported by this news organization.

“Just to see diabetes front and center at the State of the Union followed by these announcements is certainly reflective of our own advocacy effort to make sure that people have affordable options for insulin, diabetes medications, services,” Kate Thomas, ADCES chief advocacy and external affairs officer, said in an interview. She added that ADCES has also pushed for legislation in Congress that would expand access to diabetes self-management training under the Medicare program.

The guide includes advice about overcoming barriers to discussing treatment costs with patients, suggested questions to ask patients about specific costs, and determinants of health and conversational approaches. Links are provided to resources for obtaining affordable insulin, other diabetes medications, and continuous glucose monitoring and insulin pump equipment.

“We know that, especially during primary care visits, there is limited time along with numbers of issues to talk about, so I think our challenge is how do we prioritize these conversations with something that can lead to action, not just saying you should do this but how do you actually do it,” Ms. Thomas said.

The introduction summarizes results from a 2021 Beyond Type 1 survey confirming prior findings reported by this news organization that cost is a frequent barrier for many individuals living with diabetes. “Especially right now where we are in terms of the impact of the pandemic and with peoples’ job statuses changing, I think it’s worthwhile to raise this in patient encounters,” Ms. Thomas said.
 

Overcoming conversational barriers

The first of three tables in the guide provides a list of “barriers to having a cost conversation” in the first column and “suggested solutions” in the second. For example, for the barrier, “You have insufficient time and/or knowledge about cost,” the suggestion is, “request and share available faculty and resources, including benefits coordinators, social workers, and community-based organizations. Work with the pharmacists and other members of the diabetes care team to identify resources that lower cost of medications.”

And for another barrier, “patients are often embarrassed or ashamed to initiate discussions of affordability,” the suggested solution is: “Normalize the issue of cost of care barriers for patients.”

A second table offers specific questions to ask patients about costs of medications and care, determinants of health, and financial barriers. These include: “What are some challenges you’ve had to accessing your medications or taking them as prescribed? What are some out-of-pocket health care costs you need help with? What challenges do you have accessing healthy food for you and your family?”

A link to a screening tool for social determinants of health is also included.

Language suggestions include talking about “cost of care” rather than “money,” asking patients if they’ve understood everything correctly by repeating back what they’ve said, and asking for confirmation and discussing follow-up.

Overall, the tool is designed to be a “broad conversation starter,” and not just about medications, Ms. Thomas said. “This is for all audiences and it’s meant to be something that the provider can tailor depending on who they’re speaking to. ... It’s about medications, but also the entire cost of care, including services and devices, transportation to appointments, access to food. ... Diabetes care isn’t just taking medication. It’s so many more factors.”

Ms. Thomas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

As public attention continues to focus on making insulin affordable, a new online guide is available to help clinicians approach discussions with patients about diabetes medication affordability and access.

The resource, “Having Healthcare Cost Conversations to Improve Patient Outcomes: A Practical Guide,” was jointly developed by the Association of Diabetes Care & Education Specialists and Beyond Type 1, the nonprofit patient advocacy organization.

Indeed, the guide appeared as President Biden discussed his proposal to cap insulin costs at $35 per insulin vial during the State of the Union address, during which he introduced a young boy with type 1 diabetes in the guest box, as reported by this news organization. On March 3, Civica, a nonprofit coalition of health systems and philanthropies, announced it plans to manufacture generic insulin at a deeply discounted price, as reported by this news organization.

“Just to see diabetes front and center at the State of the Union followed by these announcements is certainly reflective of our own advocacy effort to make sure that people have affordable options for insulin, diabetes medications, services,” Kate Thomas, ADCES chief advocacy and external affairs officer, said in an interview. She added that ADCES has also pushed for legislation in Congress that would expand access to diabetes self-management training under the Medicare program.

The guide includes advice about overcoming barriers to discussing treatment costs with patients, suggested questions to ask patients about specific costs, and determinants of health and conversational approaches. Links are provided to resources for obtaining affordable insulin, other diabetes medications, and continuous glucose monitoring and insulin pump equipment.

“We know that, especially during primary care visits, there is limited time along with numbers of issues to talk about, so I think our challenge is how do we prioritize these conversations with something that can lead to action, not just saying you should do this but how do you actually do it,” Ms. Thomas said.

The introduction summarizes results from a 2021 Beyond Type 1 survey confirming prior findings reported by this news organization that cost is a frequent barrier for many individuals living with diabetes. “Especially right now where we are in terms of the impact of the pandemic and with peoples’ job statuses changing, I think it’s worthwhile to raise this in patient encounters,” Ms. Thomas said.
 

Overcoming conversational barriers

The first of three tables in the guide provides a list of “barriers to having a cost conversation” in the first column and “suggested solutions” in the second. For example, for the barrier, “You have insufficient time and/or knowledge about cost,” the suggestion is, “request and share available faculty and resources, including benefits coordinators, social workers, and community-based organizations. Work with the pharmacists and other members of the diabetes care team to identify resources that lower cost of medications.”

And for another barrier, “patients are often embarrassed or ashamed to initiate discussions of affordability,” the suggested solution is: “Normalize the issue of cost of care barriers for patients.”

A second table offers specific questions to ask patients about costs of medications and care, determinants of health, and financial barriers. These include: “What are some challenges you’ve had to accessing your medications or taking them as prescribed? What are some out-of-pocket health care costs you need help with? What challenges do you have accessing healthy food for you and your family?”

A link to a screening tool for social determinants of health is also included.

Language suggestions include talking about “cost of care” rather than “money,” asking patients if they’ve understood everything correctly by repeating back what they’ve said, and asking for confirmation and discussing follow-up.

Overall, the tool is designed to be a “broad conversation starter,” and not just about medications, Ms. Thomas said. “This is for all audiences and it’s meant to be something that the provider can tailor depending on who they’re speaking to. ... It’s about medications, but also the entire cost of care, including services and devices, transportation to appointments, access to food. ... Diabetes care isn’t just taking medication. It’s so many more factors.”

Ms. Thomas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

As public attention continues to focus on making insulin affordable, a new online guide is available to help clinicians approach discussions with patients about diabetes medication affordability and access.

The resource, “Having Healthcare Cost Conversations to Improve Patient Outcomes: A Practical Guide,” was jointly developed by the Association of Diabetes Care & Education Specialists and Beyond Type 1, the nonprofit patient advocacy organization.

Indeed, the guide appeared as President Biden discussed his proposal to cap insulin costs at $35 per insulin vial during the State of the Union address, during which he introduced a young boy with type 1 diabetes in the guest box, as reported by this news organization. On March 3, Civica, a nonprofit coalition of health systems and philanthropies, announced it plans to manufacture generic insulin at a deeply discounted price, as reported by this news organization.

“Just to see diabetes front and center at the State of the Union followed by these announcements is certainly reflective of our own advocacy effort to make sure that people have affordable options for insulin, diabetes medications, services,” Kate Thomas, ADCES chief advocacy and external affairs officer, said in an interview. She added that ADCES has also pushed for legislation in Congress that would expand access to diabetes self-management training under the Medicare program.

The guide includes advice about overcoming barriers to discussing treatment costs with patients, suggested questions to ask patients about specific costs, and determinants of health and conversational approaches. Links are provided to resources for obtaining affordable insulin, other diabetes medications, and continuous glucose monitoring and insulin pump equipment.

“We know that, especially during primary care visits, there is limited time along with numbers of issues to talk about, so I think our challenge is how do we prioritize these conversations with something that can lead to action, not just saying you should do this but how do you actually do it,” Ms. Thomas said.

The introduction summarizes results from a 2021 Beyond Type 1 survey confirming prior findings reported by this news organization that cost is a frequent barrier for many individuals living with diabetes. “Especially right now where we are in terms of the impact of the pandemic and with peoples’ job statuses changing, I think it’s worthwhile to raise this in patient encounters,” Ms. Thomas said.
 

Overcoming conversational barriers

The first of three tables in the guide provides a list of “barriers to having a cost conversation” in the first column and “suggested solutions” in the second. For example, for the barrier, “You have insufficient time and/or knowledge about cost,” the suggestion is, “request and share available faculty and resources, including benefits coordinators, social workers, and community-based organizations. Work with the pharmacists and other members of the diabetes care team to identify resources that lower cost of medications.”

And for another barrier, “patients are often embarrassed or ashamed to initiate discussions of affordability,” the suggested solution is: “Normalize the issue of cost of care barriers for patients.”

A second table offers specific questions to ask patients about costs of medications and care, determinants of health, and financial barriers. These include: “What are some challenges you’ve had to accessing your medications or taking them as prescribed? What are some out-of-pocket health care costs you need help with? What challenges do you have accessing healthy food for you and your family?”

A link to a screening tool for social determinants of health is also included.

Language suggestions include talking about “cost of care” rather than “money,” asking patients if they’ve understood everything correctly by repeating back what they’ve said, and asking for confirmation and discussing follow-up.

Overall, the tool is designed to be a “broad conversation starter,” and not just about medications, Ms. Thomas said. “This is for all audiences and it’s meant to be something that the provider can tailor depending on who they’re speaking to. ... It’s about medications, but also the entire cost of care, including services and devices, transportation to appointments, access to food. ... Diabetes care isn’t just taking medication. It’s so many more factors.”

Ms. Thomas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Earlier menopause appears to be associated with a higher risk of dementia, and earlier onset of dementia, compared with menopause at normal age or later, according to a large study.

“Being aware of this increased risk can help women practice strategies to prevent dementia and to work with their physicians to closely monitor their cognitive status as they age,” study investigator Wenting Hao, MD, with Shandong University, Jinan, China, says in a news release.

The findings were presented in an e-poster March 1 at the Epidemiology, Prevention, Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference sponsored by the American Heart Association.
 

UK Biobank data

Dr. Hao and colleagues examined health data for 153,291 women who were 60 years old on average when they became participants in the UK Biobank.

Age at menopause was categorized as premature (younger than age 40), early (40 to 44 years), reference (45 to 51), 52 to 55 years, and 55+ years.

Compared with women who entered menopause around age 50 years (reference), women who experienced premature menopause were 35% more likely to develop some type of dementia later in life (hazard ratio, 1.35; 95% confidence interval, 1.22 to 1.91).

Women with early menopause were also more likely to develop early-onset dementia, that is, before age 65 (HR, 1.31; 95% confidence interval, 1.07 to 1.72).

Women who entered menopause later (at age 52+) had dementia risk similar to women who entered menopause at the average age of 50 to 51 years.

The results were adjusted for relevant cofactors, including age at last exam, race, educational level, cigarette and alcohol use, body mass index, cardiovascular disease, diabetes, income, and leisure and physical activities.

Blame it on estrogen?

Reduced estrogen levels may be a factor in the possible connection between early menopause and dementia, Dr. Hao and her colleagues say.

Estradiol plays a key role in a range of neurological functions, so the reduction of endogenous estrogen at menopause may aggravate brain changes related to neurodegenerative disease and speed up progression of dementia, they explain.

“We know that the lack of estrogen over the long term enhances oxidative stress, which may increase brain aging and lead to cognitive impairment,” Dr. Hao adds.

Limitations of the study include reliance on self-reported information about age at menopause onset.

Also, the researchers did not evaluate dementia rates in women who had a naturally occurring early menopause separate from the women with surgery-induced menopause, which may affect the results.

Finally, the data used for this study included mostly White women living in the U.K. and may not generalize to other populations.
 

Supportive evidence, critical area of research

The U.K. study supports results of a previously reported Kaiser Permanente study, which showed women who entered menopause at age 45 or younger were at 28% greater dementia risk, compared with women who experienced menopause after age 45.

Reached for comment, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, noted that nearly two-thirds of Americans with Alzheimer’s are women.

“We know Alzheimer’s and other dementias impact a greater number of women than men, but we don’t know why,” she told this news organization.

“Lifelong differences in women may affect their risk or affect what is contributing to their underlying biology of the disease, and we need more research to better understand what may be these contributing factors,” said Dr. Snyder.

“Reproductive history is one critical area being studied. The physical and hormonal changes that occur during menopause – as well as other hormonal changes throughout life – are considerable, and it’s important to understand what impact, if any, these changes may have on the brain,” Dr. Snyder added.

“The potential link between reproduction history and brain health is intriguing, but much more research in this area is needed to understand these links,” she said.

The study was funded by the Start-up Foundation for Scientific Research at Shandong University. Dr. Hao and Dr. Snyder have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Earlier menopause appears to be associated with a higher risk of dementia, and earlier onset of dementia, compared with menopause at normal age or later, according to a large study.

“Being aware of this increased risk can help women practice strategies to prevent dementia and to work with their physicians to closely monitor their cognitive status as they age,” study investigator Wenting Hao, MD, with Shandong University, Jinan, China, says in a news release.

The findings were presented in an e-poster March 1 at the Epidemiology, Prevention, Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference sponsored by the American Heart Association.
 

UK Biobank data

Dr. Hao and colleagues examined health data for 153,291 women who were 60 years old on average when they became participants in the UK Biobank.

Age at menopause was categorized as premature (younger than age 40), early (40 to 44 years), reference (45 to 51), 52 to 55 years, and 55+ years.

Compared with women who entered menopause around age 50 years (reference), women who experienced premature menopause were 35% more likely to develop some type of dementia later in life (hazard ratio, 1.35; 95% confidence interval, 1.22 to 1.91).

Women with early menopause were also more likely to develop early-onset dementia, that is, before age 65 (HR, 1.31; 95% confidence interval, 1.07 to 1.72).

Women who entered menopause later (at age 52+) had dementia risk similar to women who entered menopause at the average age of 50 to 51 years.

The results were adjusted for relevant cofactors, including age at last exam, race, educational level, cigarette and alcohol use, body mass index, cardiovascular disease, diabetes, income, and leisure and physical activities.

Blame it on estrogen?

Reduced estrogen levels may be a factor in the possible connection between early menopause and dementia, Dr. Hao and her colleagues say.

Estradiol plays a key role in a range of neurological functions, so the reduction of endogenous estrogen at menopause may aggravate brain changes related to neurodegenerative disease and speed up progression of dementia, they explain.

“We know that the lack of estrogen over the long term enhances oxidative stress, which may increase brain aging and lead to cognitive impairment,” Dr. Hao adds.

Limitations of the study include reliance on self-reported information about age at menopause onset.

Also, the researchers did not evaluate dementia rates in women who had a naturally occurring early menopause separate from the women with surgery-induced menopause, which may affect the results.

Finally, the data used for this study included mostly White women living in the U.K. and may not generalize to other populations.
 

Supportive evidence, critical area of research

The U.K. study supports results of a previously reported Kaiser Permanente study, which showed women who entered menopause at age 45 or younger were at 28% greater dementia risk, compared with women who experienced menopause after age 45.

Reached for comment, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, noted that nearly two-thirds of Americans with Alzheimer’s are women.

“We know Alzheimer’s and other dementias impact a greater number of women than men, but we don’t know why,” she told this news organization.

“Lifelong differences in women may affect their risk or affect what is contributing to their underlying biology of the disease, and we need more research to better understand what may be these contributing factors,” said Dr. Snyder.

“Reproductive history is one critical area being studied. The physical and hormonal changes that occur during menopause – as well as other hormonal changes throughout life – are considerable, and it’s important to understand what impact, if any, these changes may have on the brain,” Dr. Snyder added.

“The potential link between reproduction history and brain health is intriguing, but much more research in this area is needed to understand these links,” she said.

The study was funded by the Start-up Foundation for Scientific Research at Shandong University. Dr. Hao and Dr. Snyder have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Earlier menopause appears to be associated with a higher risk of dementia, and earlier onset of dementia, compared with menopause at normal age or later, according to a large study.

“Being aware of this increased risk can help women practice strategies to prevent dementia and to work with their physicians to closely monitor their cognitive status as they age,” study investigator Wenting Hao, MD, with Shandong University, Jinan, China, says in a news release.

The findings were presented in an e-poster March 1 at the Epidemiology, Prevention, Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference sponsored by the American Heart Association.
 

UK Biobank data

Dr. Hao and colleagues examined health data for 153,291 women who were 60 years old on average when they became participants in the UK Biobank.

Age at menopause was categorized as premature (younger than age 40), early (40 to 44 years), reference (45 to 51), 52 to 55 years, and 55+ years.

Compared with women who entered menopause around age 50 years (reference), women who experienced premature menopause were 35% more likely to develop some type of dementia later in life (hazard ratio, 1.35; 95% confidence interval, 1.22 to 1.91).

Women with early menopause were also more likely to develop early-onset dementia, that is, before age 65 (HR, 1.31; 95% confidence interval, 1.07 to 1.72).

Women who entered menopause later (at age 52+) had dementia risk similar to women who entered menopause at the average age of 50 to 51 years.

The results were adjusted for relevant cofactors, including age at last exam, race, educational level, cigarette and alcohol use, body mass index, cardiovascular disease, diabetes, income, and leisure and physical activities.

Blame it on estrogen?

Reduced estrogen levels may be a factor in the possible connection between early menopause and dementia, Dr. Hao and her colleagues say.

Estradiol plays a key role in a range of neurological functions, so the reduction of endogenous estrogen at menopause may aggravate brain changes related to neurodegenerative disease and speed up progression of dementia, they explain.

“We know that the lack of estrogen over the long term enhances oxidative stress, which may increase brain aging and lead to cognitive impairment,” Dr. Hao adds.

Limitations of the study include reliance on self-reported information about age at menopause onset.

Also, the researchers did not evaluate dementia rates in women who had a naturally occurring early menopause separate from the women with surgery-induced menopause, which may affect the results.

Finally, the data used for this study included mostly White women living in the U.K. and may not generalize to other populations.
 

Supportive evidence, critical area of research

The U.K. study supports results of a previously reported Kaiser Permanente study, which showed women who entered menopause at age 45 or younger were at 28% greater dementia risk, compared with women who experienced menopause after age 45.

Reached for comment, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, noted that nearly two-thirds of Americans with Alzheimer’s are women.

“We know Alzheimer’s and other dementias impact a greater number of women than men, but we don’t know why,” she told this news organization.

“Lifelong differences in women may affect their risk or affect what is contributing to their underlying biology of the disease, and we need more research to better understand what may be these contributing factors,” said Dr. Snyder.

“Reproductive history is one critical area being studied. The physical and hormonal changes that occur during menopause – as well as other hormonal changes throughout life – are considerable, and it’s important to understand what impact, if any, these changes may have on the brain,” Dr. Snyder added.

“The potential link between reproduction history and brain health is intriguing, but much more research in this area is needed to understand these links,” she said.

The study was funded by the Start-up Foundation for Scientific Research at Shandong University. Dr. Hao and Dr. Snyder have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with familial hypercholesterolemia (FH) who start lipid-lowering treatment earlier in life may reduce their cardiovascular risk, compared with those who don’t begin treatment early, according to results of a recent meta-analysis.

They showed a difference in the carotid intima-media thickness (IMT) between patients with and without FH that increased with age, but there was also a difference in IMT seen among patients with FH who started treatment early, compared with untreated patients with FH, Kika van Bergen en Henegouwen, of the departments of pediatrics and epidemiology and data science at Amsterdam University Medical Center, and colleagues wrote in their report, published in the Journal of Clinical Lipidology.

“The fact that the difference in IMT increases with age between FH patients and unaffected controls, and is more pronounced in studies with untreated FH patients than in studies with treated patients, suggests that starting treatment already at a young age in patients with FH is preferred,” the researchers wrote. “However, despite treatment, IMT in treated FH patients is still thicker in comparison to subjects without FH.”

The researchers identified 42 studies with among patients with FH and healthy control groups across the MEDLINE, EMBASE and Trials.gov databases up to a cutoff date of April 2020, with 39 studies specifically examining carotid IMT, 2 studies evaluating carotid and femoral IMT, and 1 study evaluating femoral IMT alone. Overall, the researchers examined IMT measurements in 3,796 patients with FH and 2,363 control group participants.

Although data on age and gender for FH and control groups were not available in 6 studies, the mean age ranged from 9 to 57 years for patients with FH and from 8 to 61 years in the control group. Men comprised just under half of both the FH and control groups.

The mean between-group difference in carotid IMT in 34 studies was 0.11 mm (95% confidence interval, 0.06-0.15 mm; P < .001) for patients with FH, compared with the control group, while the mean difference in femoral IMT in three studies was 0.47 mm (95% CI, 0.19-0.74 mm; P < .001) between FH and control groups.

In 13 studies in which data on differences between partly treated and untreated FH were available, there was a significant between-group difference in carotid IMT with partly treated patients with FH, compared with the control group (0.05 mm; 95% CI, 0.03-0.08 mm; P < .001), but a larger mean between-group difference in carotid IMT among untreated patients with FH, compared with a control group (0.12 mm; 95% CI, 0.03-0.21 mm; P = .009).

The researchers also analyzed how age impacts carotid IMT, and they found patients with FH had a mean increase of 0.0018 mm (95% CI, –0.0007 to 0.0042 mm) over a control group in 34 studies. For patients with partly treated FH, compared with patients with untreated FH, the mean between-group increase per year was smaller (0.0023 mm; 95% CI, 0.0021-0.0025 mm), compared with the control group (0.0104 mm; 95% CI, 0.0100-0.0108 mm).

“This sign of residual risk might suggest that more robust cholesterol-lowering treatment and achieving treatment targets, or earlier treatment initiation, is needed to reduce IMT progression to non-FH conditions,” the researchers said. “Therefore, we must find and diagnose these patients, and treat them according to current guidelines.”

Limitations of the authors’ meta-analyses include heterogeneity among studies, differences in IMT measurement protocols, and inclusion of studies with an open-label design. Although randomized clinical trials would be preferable to compare treatment effect, “since statin therapy is indicated in FH patients to reduce [cardiovascular disease], it would be unethical to have a placebo group,” they said.

The authors reported no relevant financial disclosures.

Patients with familial hypercholesterolemia (FH) who start lipid-lowering treatment earlier in life may reduce their cardiovascular risk, compared with those who don’t begin treatment early, according to results of a recent meta-analysis.

They showed a difference in the carotid intima-media thickness (IMT) between patients with and without FH that increased with age, but there was also a difference in IMT seen among patients with FH who started treatment early, compared with untreated patients with FH, Kika van Bergen en Henegouwen, of the departments of pediatrics and epidemiology and data science at Amsterdam University Medical Center, and colleagues wrote in their report, published in the Journal of Clinical Lipidology.

“The fact that the difference in IMT increases with age between FH patients and unaffected controls, and is more pronounced in studies with untreated FH patients than in studies with treated patients, suggests that starting treatment already at a young age in patients with FH is preferred,” the researchers wrote. “However, despite treatment, IMT in treated FH patients is still thicker in comparison to subjects without FH.”

The researchers identified 42 studies with among patients with FH and healthy control groups across the MEDLINE, EMBASE and Trials.gov databases up to a cutoff date of April 2020, with 39 studies specifically examining carotid IMT, 2 studies evaluating carotid and femoral IMT, and 1 study evaluating femoral IMT alone. Overall, the researchers examined IMT measurements in 3,796 patients with FH and 2,363 control group participants.

Although data on age and gender for FH and control groups were not available in 6 studies, the mean age ranged from 9 to 57 years for patients with FH and from 8 to 61 years in the control group. Men comprised just under half of both the FH and control groups.

The mean between-group difference in carotid IMT in 34 studies was 0.11 mm (95% confidence interval, 0.06-0.15 mm; P < .001) for patients with FH, compared with the control group, while the mean difference in femoral IMT in three studies was 0.47 mm (95% CI, 0.19-0.74 mm; P < .001) between FH and control groups.

In 13 studies in which data on differences between partly treated and untreated FH were available, there was a significant between-group difference in carotid IMT with partly treated patients with FH, compared with the control group (0.05 mm; 95% CI, 0.03-0.08 mm; P < .001), but a larger mean between-group difference in carotid IMT among untreated patients with FH, compared with a control group (0.12 mm; 95% CI, 0.03-0.21 mm; P = .009).

The researchers also analyzed how age impacts carotid IMT, and they found patients with FH had a mean increase of 0.0018 mm (95% CI, –0.0007 to 0.0042 mm) over a control group in 34 studies. For patients with partly treated FH, compared with patients with untreated FH, the mean between-group increase per year was smaller (0.0023 mm; 95% CI, 0.0021-0.0025 mm), compared with the control group (0.0104 mm; 95% CI, 0.0100-0.0108 mm).

“This sign of residual risk might suggest that more robust cholesterol-lowering treatment and achieving treatment targets, or earlier treatment initiation, is needed to reduce IMT progression to non-FH conditions,” the researchers said. “Therefore, we must find and diagnose these patients, and treat them according to current guidelines.”

Limitations of the authors’ meta-analyses include heterogeneity among studies, differences in IMT measurement protocols, and inclusion of studies with an open-label design. Although randomized clinical trials would be preferable to compare treatment effect, “since statin therapy is indicated in FH patients to reduce [cardiovascular disease], it would be unethical to have a placebo group,” they said.

The authors reported no relevant financial disclosures.

Patients with familial hypercholesterolemia (FH) who start lipid-lowering treatment earlier in life may reduce their cardiovascular risk, compared with those who don’t begin treatment early, according to results of a recent meta-analysis.

They showed a difference in the carotid intima-media thickness (IMT) between patients with and without FH that increased with age, but there was also a difference in IMT seen among patients with FH who started treatment early, compared with untreated patients with FH, Kika van Bergen en Henegouwen, of the departments of pediatrics and epidemiology and data science at Amsterdam University Medical Center, and colleagues wrote in their report, published in the Journal of Clinical Lipidology.

“The fact that the difference in IMT increases with age between FH patients and unaffected controls, and is more pronounced in studies with untreated FH patients than in studies with treated patients, suggests that starting treatment already at a young age in patients with FH is preferred,” the researchers wrote. “However, despite treatment, IMT in treated FH patients is still thicker in comparison to subjects without FH.”

The researchers identified 42 studies with among patients with FH and healthy control groups across the MEDLINE, EMBASE and Trials.gov databases up to a cutoff date of April 2020, with 39 studies specifically examining carotid IMT, 2 studies evaluating carotid and femoral IMT, and 1 study evaluating femoral IMT alone. Overall, the researchers examined IMT measurements in 3,796 patients with FH and 2,363 control group participants.

Although data on age and gender for FH and control groups were not available in 6 studies, the mean age ranged from 9 to 57 years for patients with FH and from 8 to 61 years in the control group. Men comprised just under half of both the FH and control groups.

The mean between-group difference in carotid IMT in 34 studies was 0.11 mm (95% confidence interval, 0.06-0.15 mm; P < .001) for patients with FH, compared with the control group, while the mean difference in femoral IMT in three studies was 0.47 mm (95% CI, 0.19-0.74 mm; P < .001) between FH and control groups.

In 13 studies in which data on differences between partly treated and untreated FH were available, there was a significant between-group difference in carotid IMT with partly treated patients with FH, compared with the control group (0.05 mm; 95% CI, 0.03-0.08 mm; P < .001), but a larger mean between-group difference in carotid IMT among untreated patients with FH, compared with a control group (0.12 mm; 95% CI, 0.03-0.21 mm; P = .009).

The researchers also analyzed how age impacts carotid IMT, and they found patients with FH had a mean increase of 0.0018 mm (95% CI, –0.0007 to 0.0042 mm) over a control group in 34 studies. For patients with partly treated FH, compared with patients with untreated FH, the mean between-group increase per year was smaller (0.0023 mm; 95% CI, 0.0021-0.0025 mm), compared with the control group (0.0104 mm; 95% CI, 0.0100-0.0108 mm).

“This sign of residual risk might suggest that more robust cholesterol-lowering treatment and achieving treatment targets, or earlier treatment initiation, is needed to reduce IMT progression to non-FH conditions,” the researchers said. “Therefore, we must find and diagnose these patients, and treat them according to current guidelines.”

Limitations of the authors’ meta-analyses include heterogeneity among studies, differences in IMT measurement protocols, and inclusion of studies with an open-label design. Although randomized clinical trials would be preferable to compare treatment effect, “since statin therapy is indicated in FH patients to reduce [cardiovascular disease], it would be unethical to have a placebo group,” they said.

The authors reported no relevant financial disclosures.

The past week has seen heated debate about the complex issue of how to best treat children with gender dysphoria, with further developments in a number of U.S. states and in Sweden. 

In the U.S., more states have moved to prevent the use of any medical treatment, such as puberty blockers or cross-sex hormones, in kids younger than the age of 18, most recently in a state Senate vote in Alabama last week, and in Texas, where Governor Greg Abbott is said to have ordered state agencies to investigate reports of gender-transition procedures on children as “child abuse.”

At least one parent has, because of this, established a crowdfunding page to try to raise money to move away from Texas, fearful of being accused of child abuse if their child with gender dysphoria receives hormone therapy. And a countersuit has been filed there by the ACLU of Texas and Lambda Legal, a civil rights organization, on behalf of one parent said to be under investigation.

But on the flip side, parents living in more liberal states – where children under the age of 18 can often get hormones to transition without parental consent – are considering moving out of them to protect their children. These parents are concerned that their kids do not know enough about the side effects of puberty blockers, or lifetime use of cross-sex hormones and its implications, to be able to make properly informed decisions at such a young age.  

Meanwhile, Sweden has further tightened its restrictions on medical therapy to treat gender-questioning kids, with a recent announcement from its National Board of Health and Welfare (NBHW), on Feb. 22, urging restraint in hormone treatment of minors with gender dysphoria following a review by the agency there that assesses health technologies, the SBU.

Based on the review results, the NBHW’s overall conclusion is that the risks of puberty blocking and cross-sex hormone treatment for those under 18 currently outweigh the possible benefits for the group as a whole. The agency now says hormone treatment should only be offered in exceptional cases outside the framework of research, and principally, only in adolescents with childhood-onset gender dysphoria, as opposed to those who develop it during puberty, or in their teens, as is the case with most teenagers currently presenting. 

At the same time, gender-affirming hormone treatment for adolescents who identify as transgender or nonbinary is associated with changes in depression and suicidality, according to a new U.S. survey published Feb. 25 in JAMA Network Health. 

However, experts who spoke to this news organization were critical of the study, noting it was small, conducted in just 104 youth who were an average age of 15.8 years and of whom only 63% completed the survey at the final timepoint, just 1 year after starting therapy. In addition, there was no control group, among other limitations.

“The most worrying thing is that they haven’t described the pros and cons of the treatment that they are researching. We know that there are risks inherent in using gender-affirming medicine, as with all medications,” Anna Hutchinson, DClinPsych, of the Integrated Psychology Clinic, London, told this news organization.

“For example, when people with gender dysphoria use cross-sex hormones, there is a burden of treatment that can last a lifetime, both for those who benefit from the treatment and those who detransition or regret later on,” said Dr. Hutchinson, who has extensive experience of working with young people with issues related to sexuality or gender.

“This isn’t mentioned at all, which makes the paper appear quite biased towards using one approach for managing gender dysphoria and related distress, whilst not acknowledging any risks of doing so or considering alternatives,” she noted.
 

Why were some treated with hormones while others weren’t? 

The newly published survey is by PhD student Diana M. Tordoff, MPH, of the Department of Epidemiology, University of Washington, Seattle, and colleagues. Published alongside was an invited commentary by Brett Dolotina, BS, of Massachusetts General Hospital, Boston, and Jack L. Turban, MD, MHS, of Stanford (Calif.) University.

The study was conducted at an urban multidisciplinary gender clinic in Seattle among transgender and nonbinary adolescents and young adults seeking gender-affirming care from August 2017 to June 2018. Data were analyzed from August 2020 to November 2021.

Participating in the study were 104 youths aged 13-20 years (mean age, 15.8 years), 63 transmasculine (born female) individuals (60.6%), 27 transfeminine (born male) individuals (26.0%), 10 nonbinary or gender-fluid individuals (9.6%), and four youths who responded, “I don’t know,” or did not respond to the gender-identity question (3.8%). 

At baseline, 59 individuals (56.7%) had moderate-to-severe depression, 52 individuals (50.0%) had moderate-to-severe anxiety, and 45 individuals (43.3%) reported self-harm or suicidal thoughts. 

By the end of the study, 69 youths (66.3%) had received puberty blockers, cross-sex hormones (testosterone for girls transitioning to male and estrogen for boys transitioning to female), or both interventions, while 35 youths had not received either intervention (33.7%). 

After adjustment for temporal trends and potential confounders, there were a 60% lower odds of depression (adjusted odds ratio, 0.40; 95% confidence interval, 0.17-0.95) and 73% lower odds of suicidality (aOR, 0.27; 95% CI, 0.11-0.65) among youths who had initiated puberty blockers or cross-sex hormones. 

There was no association between these treatments and anxiety, however (aOR, 1.01; 95% CI, 0.41-2.51).

Dr. Hutchinson points out that nonbinary and gender fluid “are not diagnostic or clinical terms,” adding, “there is no information about how the groups were chosen or if any of them met the criteria for gender dysphoria. It seems strange to not have measured gender dysphoria, both before and after interventions, in a group of children presenting with gender dysphoria.”

She adds: “I am questioning why ‘gender-affirming’ medicine appears to be being used here as a specific intervention for depression and suicidality? [That] wouldn’t usually be the first reason to commence these particular treatments. Why didn’t they provide therapy or antidepressant medication to this group of young people, as is routine for managing mood and/or suicidality in all other patient cohorts?”  

In their commentary, Mr. Dolotina and Dr. Turban observe: “The rate of suicidality among the Tordoff et al. sample after receiving gender-affirming care was still much higher than national rates of suicidality among youth in the U.S., denoting that ... other mental health determinants must be addressed ... including gender minority stress.”
 

Small study, no control group, large loss to follow-up

Dr. Hutchinson also criticizes the small sample size of just 104 youth and “large loss to follow-up, whereby only 65 of those 104 [youth] completed the final survey in a short time [1 year].” This could indicate “that only the most satisfied kids stayed the course,” she suggests. 

And importantly, the findings on depression and suicidality rely on the experience of only five people in the no-treatment group at 12 months, she points out. 

Also, as the authors themselves acknowledge, they didn’t control for other psychiatric medicines that the participants might have been taking at baseline.

“It’s important to know more about all of this in order to draw accurate conclusions about what works, or does not, for whom,” noted Dr. Hutchinson.

Most patients, too, she notes, were females-to-males taking testosterone. Therefore, the finding that they experienced a reduction in depression might simply reflect the widely reported antidepressant effects of testosterone. 

Also expressing concern about the small sample size and “lack of a control group” is Michelle Mackness, MC, a Canadian counselor in private practice who has experience working with gender-questioning individuals, detransitioners, and those experiencing complications related to their transition. 

“Tordoff et al.’s assertion that there is a ‘robust evidence base’ supporting pediatric transition seems out-of-step with recent global developments in care policies and protocols for gender-questioning youth,” she points out.

“Neither the study authors or commentators acknowledge, let alone address, the fact that Finland, the U.K., and Sweden have recently determined that the evidence allegedly supporting medical interventions for pediatric transition is ‘inconclusive’,” she adds. 

Asked to respond, Ms. Tordoff did not directly address this question. Rather, she reiterated to this news organization: “We found that receipt of puberty blockers and gender-affirming hormones was associated with a 60% lower odds of depression and a 73% lower odds of suicidal thoughts by the end of our study follow-up. We conducted extensive sensitivity analyses, which support the robustness of our study findings.”

She added: “These results are consistent with other recently published prospective cohort studies (please see citations provided within the manuscript).”

Parents may move states

It is this concern about the lifetime burden of treatment involved with transitioning that gives some parents of children with gender dysphoria pause for thought, especially those who live in more liberal U.S. states.

Indeed, two of America’s leading psychologists who work in this field, including one who is transgender herself, told this news organization in November they are now concerned about a lack of adequate psychological evaluations of youth with gender dysphoria before any medical treatment is considered. 

So while one parent, Violet A., last week established a GoFundMe page for her child, entitled, “Help Us Move Isa to Safety,” stating she needed to move from Texas due to Governor Abbott’s pronouncements there “to a state that won’t consider me an abuser when I seek medical care for my trans child and potentially remove her from my custody,” some parents feel the need instead to move from more liberal states.

Some tell their stories anonymously, as they don’t want to risk causing their gender-questioning children further distress, as detailed on the Genspect website.

A version of this article first appeared on Medscape.com.

The past week has seen heated debate about the complex issue of how to best treat children with gender dysphoria, with further developments in a number of U.S. states and in Sweden. 

In the U.S., more states have moved to prevent the use of any medical treatment, such as puberty blockers or cross-sex hormones, in kids younger than the age of 18, most recently in a state Senate vote in Alabama last week, and in Texas, where Governor Greg Abbott is said to have ordered state agencies to investigate reports of gender-transition procedures on children as “child abuse.”

At least one parent has, because of this, established a crowdfunding page to try to raise money to move away from Texas, fearful of being accused of child abuse if their child with gender dysphoria receives hormone therapy. And a countersuit has been filed there by the ACLU of Texas and Lambda Legal, a civil rights organization, on behalf of one parent said to be under investigation.

But on the flip side, parents living in more liberal states – where children under the age of 18 can often get hormones to transition without parental consent – are considering moving out of them to protect their children. These parents are concerned that their kids do not know enough about the side effects of puberty blockers, or lifetime use of cross-sex hormones and its implications, to be able to make properly informed decisions at such a young age.  

Meanwhile, Sweden has further tightened its restrictions on medical therapy to treat gender-questioning kids, with a recent announcement from its National Board of Health and Welfare (NBHW), on Feb. 22, urging restraint in hormone treatment of minors with gender dysphoria following a review by the agency there that assesses health technologies, the SBU.

Based on the review results, the NBHW’s overall conclusion is that the risks of puberty blocking and cross-sex hormone treatment for those under 18 currently outweigh the possible benefits for the group as a whole. The agency now says hormone treatment should only be offered in exceptional cases outside the framework of research, and principally, only in adolescents with childhood-onset gender dysphoria, as opposed to those who develop it during puberty, or in their teens, as is the case with most teenagers currently presenting. 

At the same time, gender-affirming hormone treatment for adolescents who identify as transgender or nonbinary is associated with changes in depression and suicidality, according to a new U.S. survey published Feb. 25 in JAMA Network Health. 

However, experts who spoke to this news organization were critical of the study, noting it was small, conducted in just 104 youth who were an average age of 15.8 years and of whom only 63% completed the survey at the final timepoint, just 1 year after starting therapy. In addition, there was no control group, among other limitations.

“The most worrying thing is that they haven’t described the pros and cons of the treatment that they are researching. We know that there are risks inherent in using gender-affirming medicine, as with all medications,” Anna Hutchinson, DClinPsych, of the Integrated Psychology Clinic, London, told this news organization.

“For example, when people with gender dysphoria use cross-sex hormones, there is a burden of treatment that can last a lifetime, both for those who benefit from the treatment and those who detransition or regret later on,” said Dr. Hutchinson, who has extensive experience of working with young people with issues related to sexuality or gender.

“This isn’t mentioned at all, which makes the paper appear quite biased towards using one approach for managing gender dysphoria and related distress, whilst not acknowledging any risks of doing so or considering alternatives,” she noted.
 

Why were some treated with hormones while others weren’t? 

The newly published survey is by PhD student Diana M. Tordoff, MPH, of the Department of Epidemiology, University of Washington, Seattle, and colleagues. Published alongside was an invited commentary by Brett Dolotina, BS, of Massachusetts General Hospital, Boston, and Jack L. Turban, MD, MHS, of Stanford (Calif.) University.

The study was conducted at an urban multidisciplinary gender clinic in Seattle among transgender and nonbinary adolescents and young adults seeking gender-affirming care from August 2017 to June 2018. Data were analyzed from August 2020 to November 2021.

Participating in the study were 104 youths aged 13-20 years (mean age, 15.8 years), 63 transmasculine (born female) individuals (60.6%), 27 transfeminine (born male) individuals (26.0%), 10 nonbinary or gender-fluid individuals (9.6%), and four youths who responded, “I don’t know,” or did not respond to the gender-identity question (3.8%). 

At baseline, 59 individuals (56.7%) had moderate-to-severe depression, 52 individuals (50.0%) had moderate-to-severe anxiety, and 45 individuals (43.3%) reported self-harm or suicidal thoughts. 

By the end of the study, 69 youths (66.3%) had received puberty blockers, cross-sex hormones (testosterone for girls transitioning to male and estrogen for boys transitioning to female), or both interventions, while 35 youths had not received either intervention (33.7%). 

After adjustment for temporal trends and potential confounders, there were a 60% lower odds of depression (adjusted odds ratio, 0.40; 95% confidence interval, 0.17-0.95) and 73% lower odds of suicidality (aOR, 0.27; 95% CI, 0.11-0.65) among youths who had initiated puberty blockers or cross-sex hormones. 

There was no association between these treatments and anxiety, however (aOR, 1.01; 95% CI, 0.41-2.51).

Dr. Hutchinson points out that nonbinary and gender fluid “are not diagnostic or clinical terms,” adding, “there is no information about how the groups were chosen or if any of them met the criteria for gender dysphoria. It seems strange to not have measured gender dysphoria, both before and after interventions, in a group of children presenting with gender dysphoria.”

She adds: “I am questioning why ‘gender-affirming’ medicine appears to be being used here as a specific intervention for depression and suicidality? [That] wouldn’t usually be the first reason to commence these particular treatments. Why didn’t they provide therapy or antidepressant medication to this group of young people, as is routine for managing mood and/or suicidality in all other patient cohorts?”  

In their commentary, Mr. Dolotina and Dr. Turban observe: “The rate of suicidality among the Tordoff et al. sample after receiving gender-affirming care was still much higher than national rates of suicidality among youth in the U.S., denoting that ... other mental health determinants must be addressed ... including gender minority stress.”
 

Small study, no control group, large loss to follow-up

Dr. Hutchinson also criticizes the small sample size of just 104 youth and “large loss to follow-up, whereby only 65 of those 104 [youth] completed the final survey in a short time [1 year].” This could indicate “that only the most satisfied kids stayed the course,” she suggests. 

And importantly, the findings on depression and suicidality rely on the experience of only five people in the no-treatment group at 12 months, she points out. 

Also, as the authors themselves acknowledge, they didn’t control for other psychiatric medicines that the participants might have been taking at baseline.

“It’s important to know more about all of this in order to draw accurate conclusions about what works, or does not, for whom,” noted Dr. Hutchinson.

Most patients, too, she notes, were females-to-males taking testosterone. Therefore, the finding that they experienced a reduction in depression might simply reflect the widely reported antidepressant effects of testosterone. 

Also expressing concern about the small sample size and “lack of a control group” is Michelle Mackness, MC, a Canadian counselor in private practice who has experience working with gender-questioning individuals, detransitioners, and those experiencing complications related to their transition. 

“Tordoff et al.’s assertion that there is a ‘robust evidence base’ supporting pediatric transition seems out-of-step with recent global developments in care policies and protocols for gender-questioning youth,” she points out.

“Neither the study authors or commentators acknowledge, let alone address, the fact that Finland, the U.K., and Sweden have recently determined that the evidence allegedly supporting medical interventions for pediatric transition is ‘inconclusive’,” she adds. 

Asked to respond, Ms. Tordoff did not directly address this question. Rather, she reiterated to this news organization: “We found that receipt of puberty blockers and gender-affirming hormones was associated with a 60% lower odds of depression and a 73% lower odds of suicidal thoughts by the end of our study follow-up. We conducted extensive sensitivity analyses, which support the robustness of our study findings.”

She added: “These results are consistent with other recently published prospective cohort studies (please see citations provided within the manuscript).”

Parents may move states

It is this concern about the lifetime burden of treatment involved with transitioning that gives some parents of children with gender dysphoria pause for thought, especially those who live in more liberal U.S. states.

Indeed, two of America’s leading psychologists who work in this field, including one who is transgender herself, told this news organization in November they are now concerned about a lack of adequate psychological evaluations of youth with gender dysphoria before any medical treatment is considered. 

So while one parent, Violet A., last week established a GoFundMe page for her child, entitled, “Help Us Move Isa to Safety,” stating she needed to move from Texas due to Governor Abbott’s pronouncements there “to a state that won’t consider me an abuser when I seek medical care for my trans child and potentially remove her from my custody,” some parents feel the need instead to move from more liberal states.

Some tell their stories anonymously, as they don’t want to risk causing their gender-questioning children further distress, as detailed on the Genspect website.

A version of this article first appeared on Medscape.com.

The past week has seen heated debate about the complex issue of how to best treat children with gender dysphoria, with further developments in a number of U.S. states and in Sweden. 

In the U.S., more states have moved to prevent the use of any medical treatment, such as puberty blockers or cross-sex hormones, in kids younger than the age of 18, most recently in a state Senate vote in Alabama last week, and in Texas, where Governor Greg Abbott is said to have ordered state agencies to investigate reports of gender-transition procedures on children as “child abuse.”

At least one parent has, because of this, established a crowdfunding page to try to raise money to move away from Texas, fearful of being accused of child abuse if their child with gender dysphoria receives hormone therapy. And a countersuit has been filed there by the ACLU of Texas and Lambda Legal, a civil rights organization, on behalf of one parent said to be under investigation.

But on the flip side, parents living in more liberal states – where children under the age of 18 can often get hormones to transition without parental consent – are considering moving out of them to protect their children. These parents are concerned that their kids do not know enough about the side effects of puberty blockers, or lifetime use of cross-sex hormones and its implications, to be able to make properly informed decisions at such a young age.  

Meanwhile, Sweden has further tightened its restrictions on medical therapy to treat gender-questioning kids, with a recent announcement from its National Board of Health and Welfare (NBHW), on Feb. 22, urging restraint in hormone treatment of minors with gender dysphoria following a review by the agency there that assesses health technologies, the SBU.

Based on the review results, the NBHW’s overall conclusion is that the risks of puberty blocking and cross-sex hormone treatment for those under 18 currently outweigh the possible benefits for the group as a whole. The agency now says hormone treatment should only be offered in exceptional cases outside the framework of research, and principally, only in adolescents with childhood-onset gender dysphoria, as opposed to those who develop it during puberty, or in their teens, as is the case with most teenagers currently presenting. 

At the same time, gender-affirming hormone treatment for adolescents who identify as transgender or nonbinary is associated with changes in depression and suicidality, according to a new U.S. survey published Feb. 25 in JAMA Network Health. 

However, experts who spoke to this news organization were critical of the study, noting it was small, conducted in just 104 youth who were an average age of 15.8 years and of whom only 63% completed the survey at the final timepoint, just 1 year after starting therapy. In addition, there was no control group, among other limitations.

“The most worrying thing is that they haven’t described the pros and cons of the treatment that they are researching. We know that there are risks inherent in using gender-affirming medicine, as with all medications,” Anna Hutchinson, DClinPsych, of the Integrated Psychology Clinic, London, told this news organization.

“For example, when people with gender dysphoria use cross-sex hormones, there is a burden of treatment that can last a lifetime, both for those who benefit from the treatment and those who detransition or regret later on,” said Dr. Hutchinson, who has extensive experience of working with young people with issues related to sexuality or gender.

“This isn’t mentioned at all, which makes the paper appear quite biased towards using one approach for managing gender dysphoria and related distress, whilst not acknowledging any risks of doing so or considering alternatives,” she noted.
 

Why were some treated with hormones while others weren’t? 

The newly published survey is by PhD student Diana M. Tordoff, MPH, of the Department of Epidemiology, University of Washington, Seattle, and colleagues. Published alongside was an invited commentary by Brett Dolotina, BS, of Massachusetts General Hospital, Boston, and Jack L. Turban, MD, MHS, of Stanford (Calif.) University.

The study was conducted at an urban multidisciplinary gender clinic in Seattle among transgender and nonbinary adolescents and young adults seeking gender-affirming care from August 2017 to June 2018. Data were analyzed from August 2020 to November 2021.

Participating in the study were 104 youths aged 13-20 years (mean age, 15.8 years), 63 transmasculine (born female) individuals (60.6%), 27 transfeminine (born male) individuals (26.0%), 10 nonbinary or gender-fluid individuals (9.6%), and four youths who responded, “I don’t know,” or did not respond to the gender-identity question (3.8%). 

At baseline, 59 individuals (56.7%) had moderate-to-severe depression, 52 individuals (50.0%) had moderate-to-severe anxiety, and 45 individuals (43.3%) reported self-harm or suicidal thoughts. 

By the end of the study, 69 youths (66.3%) had received puberty blockers, cross-sex hormones (testosterone for girls transitioning to male and estrogen for boys transitioning to female), or both interventions, while 35 youths had not received either intervention (33.7%). 

After adjustment for temporal trends and potential confounders, there were a 60% lower odds of depression (adjusted odds ratio, 0.40; 95% confidence interval, 0.17-0.95) and 73% lower odds of suicidality (aOR, 0.27; 95% CI, 0.11-0.65) among youths who had initiated puberty blockers or cross-sex hormones. 

There was no association between these treatments and anxiety, however (aOR, 1.01; 95% CI, 0.41-2.51).

Dr. Hutchinson points out that nonbinary and gender fluid “are not diagnostic or clinical terms,” adding, “there is no information about how the groups were chosen or if any of them met the criteria for gender dysphoria. It seems strange to not have measured gender dysphoria, both before and after interventions, in a group of children presenting with gender dysphoria.”

She adds: “I am questioning why ‘gender-affirming’ medicine appears to be being used here as a specific intervention for depression and suicidality? [That] wouldn’t usually be the first reason to commence these particular treatments. Why didn’t they provide therapy or antidepressant medication to this group of young people, as is routine for managing mood and/or suicidality in all other patient cohorts?”  

In their commentary, Mr. Dolotina and Dr. Turban observe: “The rate of suicidality among the Tordoff et al. sample after receiving gender-affirming care was still much higher than national rates of suicidality among youth in the U.S., denoting that ... other mental health determinants must be addressed ... including gender minority stress.”
 

Small study, no control group, large loss to follow-up

Dr. Hutchinson also criticizes the small sample size of just 104 youth and “large loss to follow-up, whereby only 65 of those 104 [youth] completed the final survey in a short time [1 year].” This could indicate “that only the most satisfied kids stayed the course,” she suggests. 

And importantly, the findings on depression and suicidality rely on the experience of only five people in the no-treatment group at 12 months, she points out. 

Also, as the authors themselves acknowledge, they didn’t control for other psychiatric medicines that the participants might have been taking at baseline.

“It’s important to know more about all of this in order to draw accurate conclusions about what works, or does not, for whom,” noted Dr. Hutchinson.

Most patients, too, she notes, were females-to-males taking testosterone. Therefore, the finding that they experienced a reduction in depression might simply reflect the widely reported antidepressant effects of testosterone. 

Also expressing concern about the small sample size and “lack of a control group” is Michelle Mackness, MC, a Canadian counselor in private practice who has experience working with gender-questioning individuals, detransitioners, and those experiencing complications related to their transition. 

“Tordoff et al.’s assertion that there is a ‘robust evidence base’ supporting pediatric transition seems out-of-step with recent global developments in care policies and protocols for gender-questioning youth,” she points out.

“Neither the study authors or commentators acknowledge, let alone address, the fact that Finland, the U.K., and Sweden have recently determined that the evidence allegedly supporting medical interventions for pediatric transition is ‘inconclusive’,” she adds. 

Asked to respond, Ms. Tordoff did not directly address this question. Rather, she reiterated to this news organization: “We found that receipt of puberty blockers and gender-affirming hormones was associated with a 60% lower odds of depression and a 73% lower odds of suicidal thoughts by the end of our study follow-up. We conducted extensive sensitivity analyses, which support the robustness of our study findings.”

She added: “These results are consistent with other recently published prospective cohort studies (please see citations provided within the manuscript).”

Parents may move states

It is this concern about the lifetime burden of treatment involved with transitioning that gives some parents of children with gender dysphoria pause for thought, especially those who live in more liberal U.S. states.

Indeed, two of America’s leading psychologists who work in this field, including one who is transgender herself, told this news organization in November they are now concerned about a lack of adequate psychological evaluations of youth with gender dysphoria before any medical treatment is considered. 

So while one parent, Violet A., last week established a GoFundMe page for her child, entitled, “Help Us Move Isa to Safety,” stating she needed to move from Texas due to Governor Abbott’s pronouncements there “to a state that won’t consider me an abuser when I seek medical care for my trans child and potentially remove her from my custody,” some parents feel the need instead to move from more liberal states.

Some tell their stories anonymously, as they don’t want to risk causing their gender-questioning children further distress, as detailed on the Genspect website.

A version of this article first appeared on Medscape.com.