In a potentially game-changing development, scientists with the Fralin Biomedical Research Institute at VTC have revealed a new understanding of sometimes fatal viral infections that affect the heart.
Traditionally, the focus has been on heart inflammation known as myocarditis, which is often triggered by the body’s immune response to a viral infection.
However, a new study led by James Smyth, associate professor at the Fralin Biomedical Research Institute, sheds new light on this notion, revealing that the virus itself creates potentially dangerous conditions in the heart before inflammation sets in.
The discovery, now online and set to appear in the March 29 issue of Circulation Research, suggests completely new directions to diagnose and treat viral infections affecting the heart.
Given the high incidence of viral-related myocarditis leading to sudden cardiac death, the insight is crucial. Up to 42 percent of sudden cardiac deaths in young adults are attributed to myocarditis, and of these cases viral infection is the leading cause.
From a clinical perspective, our understanding of viral infection of the heart has focused on inflammation, causing problems with the rate or rhythm of the heartbeat. But we have found an acute stage when the virus first infects the heart and before the body’s immune response causes inflammation. So even before the tissue is inflamed, the heart is being set up for arrhythmia.”
James Smyth, Associate Professor, Fralin Biomedical Research Institute
To make this discovery, researchers focused on adenovirus, a common culprit in cardiac infection and myocarditis, using Mouse Adenovirus Type-3 to replicate the human infection process.
They found that early in the infection, the virus disrupts critical components of the heart’s communication and electrical systems.
As a result, even before symptoms appear, the adenoviral infection creates conditions that disrupt the heart’s gap junctions and ion channels, according to virologist Rachel Padget, the study’s first author who worked in the Smyth lab while completing a doctoral degree from the Virginia Tech Translational Biology, Medicine, and Health graduate program.
Gap junctions are like tiny tunnels between heart cells that allow them to communicate, and ion channels are like gates in the cell membranes that help maintain the right balance of ions needed for the heart to generate normal patterns of electrical activity that allow it to beat properly.
When adenoviral infection disturbs these communication bridges and gatekeepers, it creates a situation where the heart might develop irregular patterns of electrical activity called arrhythmias affecting its mechanical beating and blood pumping capacity, and that can lead to sudden cardiac problems, especially in people with active infections.
Now, by targeting specific heart changes induced by viral infections at the molecular level, researchers aim to reduce the risk of cardiac issues in people grappling with viral illnesses.
“Individuals who have acute infections can look normal by MRI and echocardiography, but when we delved into the molecular level, we saw that something very dangerous could occur,” Smyth said. “In terms of diagnostics, we can now work with our colleagues here to start looking ways to analyze blood for a biomarker of the more serious problem. People get cardiac infections all the time and they recover. But can we identify what’s different about individuals that are at a higher risk to have the arrhythmia, possibly through a simple blood test in the doctor’s office.”
Smyth is also a member of the Department of Biological Sciences of the Virginia Tech College of Science.
The work was supported in part by grants from the National Institutes of Health, American Heart Association, Fralin Biomedical Research Institute Seale Innovation Fund and Lyerly Postdoctoral Excellence Award.
Source:
Journal reference:
Padget, R. L., et al. (2024). Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis. Circulation Research. doi.org/10.1161/circresaha.122.322437
Mass General Brigham, a leading integrated academic health care system, and the Healthcare Transformation Lab at Massachusetts General Hospital are proud to announce their collaboration with AvoMD, a digital clinical decision support platform that brings current medical evidence into the clinical workflow, to develop a series of inpatient emergency clinical care algorithms. This collaboration intends to empower trainee and experienced rapid response leaders to perform effectively under high stakes clinical pressure.
Mass General Brigham will work with AvoMD to translate its proprietary suite of guided algorithms for rapid response clinical scenarios onto the AvoMD application, a tool that provides efficient management guidance directly in the clinical workflow. Leveraging AvoMD’s “drag and drop” Builder platform, these algorithms can be customized and implemented by individual users, reducing the need for IT resourcing to deploy clinical pathways. Initial algorithms of focus include emergency decision support for tachycardia (fast heart rate), bradycardia (slow heart rate), hypotension (low blood pressure), hypoxia (low oxygen), and altered mental status. Through AvoMD, these algorithms will be available for other healthcare organizations to adopt and customize to their own needs and workflows.
Leading hospital rapid response and cardiac arrest teams can be one of the most stressful responsibilities faced by healthcare providers. Variability in knowledge, training, and experience can lead to inconsistent care and patient outcomes. By creating a digital suite of evidence-based rapid response clinical care algorithms, our team strives to facilitate the practice of high quality, evidence-based care during the most stressful and cognitively demanding clinical situations.”
Mike Senter-Zapata, M.D., lead clinical content provider at Mass General Brigham and the Healthcare Transformation Lab at Massachusetts General Hospital
AvoMD drives clinician adoption of key initiatives across quality, cost reduction, and reimbursement by turning lengthy pages of medical guidelines and protocols into streamlined and easily accessible clinical tools. AvoMD’s Point-of-Care App, available inside or outside of the EHR, surfaces system-specific guidelines in an actionable format and automatically populates patient information to assist with decision-making, documentation, ordering, Hierarchical Condition Category (HCC) coding, and more. In addition to leveraging their own content, organizations can use pre-built templates from medical societies such as the AHA, GOLD, KDIGO, AACE, and academic medical systems like Mass General Brigham, to equip their clinicians with actionable, best-in-class guidance from leading medical experts and professional organizations. Randomized controlled trials and implementations have shown that AvoMD provides clinicians significant efficiency gains at the point-of-care, while improving patient outcomes and reducing costs.
“AvoMD is thrilled to team up with Mass General Brigham in its goal to deliver exceptional patient care in a rapid response setting,” expressed AvoMD Co-Founder and Head of Product and Engineering, Joongheum Park, M.D. “Integrating Mass General Brigham’s expert guidance into the AvoMD platform will empower clinicians to make swift, well-informed decisions based on the latest medical evidence and highest clinical standards.”
The impact of this collaboration on clinician efficiency and confidence will be measured and studied by the Healthcare Transformation Lab, a research team at Massachusetts General Hospital focused on improving the experience and value of healthcare by inspiring collaborative innovation and leveraging novel technologies. AvoMD’s native analytics will be used to provide additional insights on usage context, and this collaborative, data-driven approach will enable both organizations to continuously refine and optimize care delivery.
In a recent study published in Frontiers in Nutrition, researchers explore the relationship between dietary intake of live microorganisms and cardiovascular health (CVH) outcomes among adults in the United States.
Despite advancements in the development of lipid-lowering drugs, cardiovascular disease (CVD) remains a significant cause of death throughout the world, thus impacting economic and social development.
Dietary patterns are implicated in poor CVH, as gut microbiota convert many nutrients into metabolites. This relationship led to the introduction of Life’s Essential 8 (LE8) by the American Heart Association to improve CVH and reduce CVD.
The LE8 covers four health factors, including blood pressure (BP), body mass index (BMI), blood glucose, and blood lipids, as well as four health behaviors of sleep health, nicotine exposure, physical activity (PA), and diet. However, the relationship between live microorganisms in the diet and LE8 is poorly understood.
About the study
Data for the current study were obtained from the National Health and Nutrition Examination Survey (NHANES) and included seven survey rounds from 2005 to 2018. All study participants were over 20 years of age and provided information on their dietary live microbial intake, LE8, sample weights, and other relevant covariates.
Live microbial quantity per gram was quantified from 9,388 food items, and study participants provided detailed dietary intake information during in-person interviews and telephonic follow-up calls. This information was subsequently used to classify study participants with low, medium, and high levels of live microbe content.
LE8 scores were calculated as an unweighted average of the eight indicators and ranged from zero to 100. Based on this score, individuals in the range of 80-100 points were classified as having high CVH, 50-79 points were considered medium CVH, and zero to 49 points were classified as having low medium.
Race and ethnicity, gender, age, education, marital status, socioeconomic status, health insurance, alcohol consumption, obesity status, daily nutrient intake, and medical history were included as additional covariates. Chi-square tests, one-way analysis of variance (ANOVA), and linear regression models were used to analyze the dataset.
Study findings
After applying exclusion criteria, 10,531 people were included in the final analysis. Females accounted for slightly more than half of the study cohort, with an average age of about 48 years.
Non-Hispanic White was the predominant ethnicity. Most study participants had at least a college education and health insurance, drank alcohol, and reported being married or in cohabiting relationships.
Most study participants were obese; nearly 9% had CVD, 14% had diabetes mellitus, about 37% had hypertension, and over 70% had hyperlipidemia. About 66% of the study cohort reported a moderate level of CVH. Across CVH levels, participants were similar in terms of daily intake of carbohydrates, hypertension, and hyperlipidemia but significantly different in other aspects.
Significant associations were observed between groups of dietary live microbes and LE8 scores, both in crude models and after adjusting for multiple covariates. For all components of LE8, a higher intake of live microorganisms was associated with better health behaviors and health factor scores.
Those in the high and moderate microorganism groups had lower CVD risk with odds ratios of 0.65 and 0.73, respectively. Notably, in the low-intake group, LE8 score and food intake had a linear negative association, whereas this association was positive in the high-intake group. The moderate microorganism intake group exhibited an inverted ‘U’ shape regarding the relationship between LE8 and food intake.
Conclusions
Probiotic supplements can reduce oxidative stress, improve immunity, and reduce blood glucose and blood pressure levels, which could maintain CVH. The current study expanded on previous studies that used self-reported medical history to characterize CVD. Taken together, these findings provide strong evidence supporting the consumption of more foods rich in live microorganisms to improve CVH outcomes.
Future studies are needed to identify individuals who may respond differently to microbial consumption based on gender and ethnicity. For example, non-Hispanic black individuals did not exhibit a significant association with live microbe consumption and CVH.
Additional research is also needed to elucidate these associations’ mechanisms and include more diverse cohorts. These types of studies have the potential to overcome the limitations of a cross-sectional study based on dietary recall data to establish causality.
Journal reference:
Wang, L., Wang, S., Wang. Y., et al. (2024). Association between dietary live microbe intake and Life’s Essential 8 in US adults: a cross-sectional study of NHANES 2005-2018. Frontiers in Nutrition (2024). doi:10.3389/fnut.2024.1340028
Aortic aneurysms are bulges in the aorta, the largest blood vessel that carries oxygen-rich blood from the heart to the rest of the body. Smoking, high blood pressure, diabetes, or injury can all increase the risk of aneurysms, which tend to occur more often in Caucasian male smokers over the age of 65.
The soft tissues that make up blood vessels act essentially like rubber bands, and it’s the elastic fibers within these tissues that allow them to stretch and snap back. These fibers are produced primarily before and just after birth. After that, they don’t regenerate or undergo natural repair after injury. So when they become injured or diseased, the tissue weakens and causes an aneurysm, which can grow over time. After about seven to 10 years, it typically reaches the rupture stage.”
Professor Anand Ramamurthi, Chair of the Department of Bioengineering in Lehigh University’s P.C. Rossin College of Engineering and Applied Science
During that period, there is no treatment. Patients are screened regularly via imaging to monitor the rate of the aneurysm’s growth. Once it’s deemed big enough to potentially rupture (an occurrence that is fatal 90 percent of the time), surgery is the only option. But it’s a risky one for elderly patients.
Ramamurthi and his team are working on minimally invasive ways to regenerate and repair these elastic fibers using polymeric or biological nanocapsules, called nanoparticles, that are designed to release novel regenerative therapeutics. Their innovative techniques could enable treatment soon after an aneurysm is detected and potentially slow, reverse, or even stop its growth. Findings from their most recent paper, published in the Journal of Biomedical Materials Research, build on their earlier work and represent a step toward a future where surgery is no longer the best, and only, treatment option.
“In previous research, we’ve identified drugs and gene-silencing agents that can actually coax adult diseased vascular cells to produce new elastic fibers and inhibit the enzymes that break down existing fibers,” he says. “We’ve also been working on how to deliver these therapeutics efficiently only at the site of tissue repair.”
The team has also developed a nanoparticle design called active-targeting that incorporates small protein fragments, or peptides, on the nanoparticle’s surface. “These peptides recognize components that are unique to the aneurysm tissue. So when the nanoparticles are injected into the bloodstream, they stick only to the aneurysm wall, where they slowly degrade and release the drug.
For this paper, he says, the researchers “investigated how the nanoparticles actually penetrate the blood vessel wall to deliver the drug to the affected tissue.”
All blood vessels are lined with a protective barrier made of endothelial cells, which can become “leaky” as inflammation from tissue damage or disease breaks down the endothelium and creates gaps between the cells. These gaps allow white blood cells to move in and start the tissue repair process, and they also serve as the entry point for nanoparticles that accelerate healing.
“We wanted to know how the shape and the aspect ratio of these nanoparticles affect their ability to cross that endothelial cell barrier,” says Ramamurthi.
It was a critical question to answer because not all nanoparticles are created alike, and if they can’t penetrate the barrier, they can’t repair the tissue.
Ramamurthi and his team developed a novel cell culture model in which they simulated disease and then examined mechanisms of transport: specifically, how nanoparticles of different kinds interacted with endothelial cells and moved through them. Did they enter through gaps among the endothelial cells (a process called extravasation) or through the cells themselves (what’s known as translocation)?
“Let’s say a nanoparticle goes through an endothelial cell. Some of it might stay within that cell and not come out the other side, which means you lose that particle, and it’s no longer useful to the healing process. The goal is transportation with minimal retention.”
The team found that rod-shaped particles, as opposed to spherical particles, with a high aspect ratio (i.e., long and skinny versus short and stubby) were selectively taken up by diseased endothelial cells. “And they showed very little uptake into healthy endothelial cells compared with the spheres, which is good because we don’t want them interacting with healthy vessel walls,” he says.
They also found that particles reached the tissue primarily by extravasation (or via the cell gaps). “The longer and skinnier they were, the less likely they were to remain within the endothelial cell layer, which means they’re getting through to the affected tissue for more effective therapy.”
The team will now integrate these findings with their work on active targeting-;incorporating components on the surface of nanoparticles that recognize proteins expressed by diseased cells-;in animal models.
The ultimate goal is to develop a nonsurgical regenerative therapy capable of slowing aneurysm growth. For example, increasing the current growth-to-rupture stage from seven years to 15 years. An even more ambitious outcome, says Ramamurthi, would be to revert that growth.
“Regression of aneurysm growth would be the preferred long-term outcome,” he says. “That’s a long way off, but we’re excited because these findings will help guide us on how to design our nanoparticles for more efficient delivery to the aneurysm wall. It’s an opportunity to get closer to that reality.”
Source:
Journal reference:
Yau, J., et al. (2024). Assessing trans‐endothelial transport of nanoparticles for delivery to abdominal aortic aneurysms. Journal of Biomedical Materials Research Part A. doi.org/10.1002/jbm.a.37667.
Participants in the Framingham Heart Study who achieved higher levels of education tended to age more slowly and went on to live longer lives as compared to those who did not achieve upward educational mobility, according to a new study at Columbia University Mailman School of Public Health and The Robert N. Butler Columbia Aging Center. Upward educational mobility was significantly associated with a slower pace of aging and lower risk of death. The results are published online in JAMA Network Open.
The Framingham Heart Study is an ongoing observational study first initiated in 1948 that currently spans three generations.
The Columbia analysis is the first to connect educational mobility with pace of biological aging and mortality.
We’ve known for a long time that people who have higher levels of education tend to live longer lives. But there are a bunch of challenges in figuring out how that happens and, critically, whether interventions to promote educational attainment will contribute to healthy longevity.”
Daniel Belsky, PhD, associate professor of Epidemiology at Columbia Mailman School and the Aging Center and senior author of the paper
To measure pace of aging, the researchers applied an algorithm known as the DunedinPACE epigenetic clock to genomic data collected by the Framingham Heart Study. The latest findings showed that, according to the yardstick of the DunedinPACE epigenetic clock, two years of additional schooling translated to a two- to three percent slower pace of aging. This slowing in the pace of aging corresponds to a roughly 10 percent reduction in risk of mortality in the Framingham Heart Study, according to previous research by Belsky on the association of DunedinPACE with risk of death.
DunedinPACE was developed by the Columbia researchers and colleagues and reported in January 2022. Based on an analysis of chemical tags on the DNA contained in white blood cells, or DNA methylation marks, DunedinPACE is named after the Dunedin Study birth cohort used to develop it. DunedinPACE (stands for Pace of Aging Computed from the Epigenome), is measured from a blood test and functions like a speedometer for the aging process, measuring how fast or slow a person’s body is changing as they grow older.
Biological aging refers to the accumulation of molecular changes that progressively undermine the integrity and resilience capacity of our cells, tissues and organs as we grow older.
The Columbia researchers used data from 14,106 Framingham Heart Study spanning three generations to link children’s educational attainment data with that of their parents. They then used data from a subset of participants who provided blood samples during data collection to calculate the pace of biological aging using the DunedinPACE epigenetic clock. In primary analysis, the researchers tested associations between educational mobility, aging, and mortality in a subset of 3,101 participants for whom educational mobility and pace of aging measures could be calculated.
For 2,437 participants with a sibling, the researchers also tested whether differences in educational attainment between siblings was associated with a difference in the pace of aging.
“A key confound in studies like these is that people with different levels of education tend to come from families with different educational backgrounds and different levels of other resources,” explained Gloria Graf, a PhD candidate in the Department of Epidemiology supervised by Belsky, and first author of the study. “To address these confounds, we focused on educational mobility, how much more (or less) education a person completed relative to their parents, and sibling differences in educational attainment – how much more (or less) education a person completed relative to their siblings. These study designs control for differences between families and allow us to isolate the effects of education.”
By combining these study designs with the new DunedinPACE epigenetic clock, the researchers were able to test how education affects the pace of aging. Then, by linking the education and pace of aging data with longitudinal records of how long participants lived, the team was able to determine if a slower pace of aging accounted for increased longevity in people with more education.
“Our findings support the hypothesis that interventions to promote educational attainment will slow the pace of biological aging and promote longevity,” noted Graf. “Ultimately, experimental evidence is needed to confirm our findings,” added Belsky. “Epigenetic clocks like DunedinPace have potential to enhance such experimental studies by providing an outcome that can reflect impacts of education on healthy aging well before the onset of disease and disability in later life.”
“We found that upward educational mobility was associated both with a slower pace of aging and decreased risk of death,” said Graf. “In fact, up to half of the educational gradient in mortality we observed was explained by healthier aging trajectories among better-educated participants.” This pattern of association was similar across generations and held within family sibling comparisons: siblings with higher educational mobility tended to have a slower pace of aging as compared with their less educated siblings.
Co-authors are Calen Ryan, Meeraj Kothari, and Alison Aiello, Columbia Mailman School of Public Health and Butler Columbia Aging Center; Peter Muennig, Columbia Mailman School of Public Health; Terrie Moffitt, Avshalom Caspi, and Karen Sugden, Duke University; and Hexuan Liu, University of Cincinnati.
The study was supported by the National Institutes of Health, grants R01AG073402, R01AG073207, and R21AG078627.
Graf, G. H. J., et al. (2024). Educational Mobility, Pace of Aging, and Lifespan Among Participants in the Framingham Heart Study. JAMA Network Open. doi.org/10.1001/jamanetworkopen.2024.0655.
A recent study published in The American Journal of Clinical Nutritiondiscusses possible associations between the national taxation of sugar-sweetened beverages (SSBs) and lowered rates of adverse health outcomes.
The consumption of SSBs or soft drinks has significantly increased throughout the world over the past several decades. This has been associated with rising rates of weight gain, a higher risk of obesity, type 2 diabetes, and heart disease, as well as a higher risk of cardiovascular disease and mortality if consumed over the long term.
Previously, the Global Burden of Disease study showed that deaths linked to soft drink intake rose between 1990 to 2019. This was accompanied by a rising number of disability-adjusted life years (DALYs) and the number of years lived with disability, the latter of which doubled during this period.
In 2009, the American Heart Association (AHA) suggested that added sugars should not exceed 100 and 150 calories each day for females and males, respectively. The World Health Organization (WHO) also limits daily free sugar intake to less than 10% of daily energy intake.
Many countries have imposed a tax on SSBs to raise revenue and limit their consumption. Some research shows that when the price of SSBs increases by 20%, their consumption may decline to similar levels. However, this prediction has not been supported by any study on global SSB consumption in relation to national tax policies and population health impact.
The current study aimed to summarize national taxation policies on SSBs throughout the world and estimate the impact of tax laws made after 1990 on population-level metabolic parameters like obesity and type 2 diabetes.
What did the study show?
Since 1990, SSB taxation has occurred in 53 countries, 24 of which were high-income countries (HIC), whereas 18 and 10 were upper-middle-income and lower-middle-income countries, respectively. Rwanda was the only low-income country to impose SSB taxation.
All but eight of the laws were implemented after 2000. In 15 countries, laws changed the tax amounts over time.
Most of the analyzed laws were a single amount based on the volume of the product, whereas a minority were based only on the sugar content of the beverage. The remaining laws were ad valorem taxes and imposed according to the product’s value.
The lowest and highest taxation per volume of the product was for Vanuatu and Thailand, as compared to Tonga and Norway, respectively. Median tax amounts in both purchasing power parities (PPPs) and United States dollars (USD) were about 0.3 and 0.16, respectively, per liter. For HICs, median tax amounts in PPPs and USD were 0.25 and 0.2, respectively, compared to 0.356 and 0.17 for lower-middle-income countries.
Some countries taxed SSBs based on the sugar content per gram of sugar for all SSBs. Comparatively, in France, SSBs were taxed for every kg of sugar plus per liter if a product had over 15 kg of sugar per 100 liters.
The median ad valorem tax amount for HICs was 50% compared to 10% and 340% for upper and lower-middle-income countries, respectively. Although a low-income country, Rwanda also had ad valorem taxation on SSBs.
Only one country, Hungary, showed a significant reduction in the slope of overweight prevalence after taxation was implemented. However, a slowing trend was observed in Paraguay.
Obesity rates declined in Brazil, Hungary, and Panama, with slowing trends observed in El Salvador, Honduras, and France. A significant reduction in obesity levels was observed in Panama and Paraguay following taxation.
Diabetes prevalence also declined in Hungary after the tax was introduced, while Finland and Guatemala showed a reduction in the slope. Honduras, Hungary, and Fiji also exhibited slowing post-taxation trends.
Similar findings were observed among children and adolescents. Samoa was associated with reduced overweight individuals, whereas five countries, including Brazil, Palau, and Samoa, showed a slope reduction, with post-intervention slowing trends observed.
The prevalence of obesity declined after taxation in El Salvador, Uruguay, and Tonga, whereas slope reductions were observed in Nauru, Palau, and Tonga. Slowing trends were observed in four countries, including Brazil and Uruguay.
Overall, ad valorem taxation was associated with larger slope reductions for diabetes among adults as compared to amount-specific taxes. However, the change in the slope of obesity among adults was associated with the year of tax implementation. Slope reductions for overweight children and adolescents were observed in upper-middle-income countries.
What are the implications?
The evidence that taxation of SSBs was associated with health-related outcomes like diabetes, overweight, and obesity was stronger among children than adults. Previous studies showed stronger correlations among adults than observed in this study; however, similar results were observed among children. Of 17 countries reporting level or slope changes, most exhibited a change associated with one or more indicators for one or more population groups.
SSB taxation could be an effective policy intervention to improve the population’s health.”
The variation in tax design could be partly due to the imbalance in the number of countries in each group, with amount-specific taxes more common. Limited data availability after the introduction of taxation may have skewed the results, along with too short a period of observation.
Taxation on a food product may convey negative sentiments to consumers; however, this effect was not studied in the current study. Reverse causality must also be excluded since, if SSB consumption was already declining, taxation might have become feasible without the fear of political losses.
There is a need to identify factors that predict the effectiveness of taxation as a strategy to reduce SSB consumption and improve related health outcomes at various levels. Other public health strategies should be simultaneously applied, especially education about the adverse effects of SSB consumption and behavioral interventions to break unhealthy consumption patterns.
Journal reference:
Sassano, M., Castagna, C., Villani, L., et al. (2024). National taxation on sugar-sweetened beverages and its association with overweight, obesity, and diabetes. The American Journal of Clinical Nutrition. doi:10.1016/j.ajcnut.2023.12.013.
A research project led by Lobelia Samavati, M.D., professor of internal medicine and molecular medicine and genetics at the Wayne State University School of Medicine, and supported by the National Institutes of Health (NIH), has developed a tool to rapidly and inexpensively diagnose sarcoidosis, a chronic inflammatory disease marked by the growth of tiny lumps called granulomas in the lungs and other organs. The tool, which uses a simple blood test, could allow for selective use of more invasive diagnostic tests often used to identify the disease. The findings were published in the American Journal of Respiratory and Critical Care Medicine.
Currently, diagnosing sarcoidosis isn’t a straightforward process and requires tissue removal and testing with additional screenings to rule out other diseases, such as tuberculosis or lung cancer. Using a blood test will help diagnose faster, particularly in those organs that are more challenging to biopsy and with less harm to the patient.”
James Kiley, Ph.D., Director of the NIH’s Division of Lung Diseases at the National Heart, Lung, and Blood Institute (NHLBI)
Though the exact cause of sarcoidosis is unknown, researchers suspect it is an immune disorder triggered by a group of specific antigens, which are generally foreign substances that incite an immune response in the body. In the United States, an estimated 8-11 people per 100,000 are affected by sarcoidosis each year, according to previous research.
To identify antigens and determine which might be linked to sarcoidosis, scientists collected lung fluid samples and blood cells from patients with pulmonary sarcoidosis, then extracted the genetic material. Using a combination of molecular techniques, the researchers homed in on two newly described disease-specific antigen biomarkers that only bind to the antibodies of sarcoidosis positive patients.
They next designed a highly specific blood test, which only requires a small amount of blood, to determine if they could accurately detect sarcoidosis. To verify the test, researchers compared blood samples from 386 people, which included patients with sarcoidosis, patients with tuberculosis, patients with lung cancer and healthy individuals. The researchers confirmed that their test was able to differentiate patients who had sarcoidosis from those with other respiratory diseases.
“More testing needs to be completed before this screening method is ready for clinical use, but it’s possible that could be a reality within a few years,” said Samavati.
“Dr. Samavati’s important work is an excellent example of how scientific research can have promising results that may lead to addressing major health challenges,” said Ezemenari M. Obasi, Ph.D., vice president for research at Wayne State University. “I look forward to the potential impact this research will have on the lives of those inflicted with sarcoidosis.”
Source:
Journal reference:
Peng, C., et al. (2024). Discovery of Two Novel Immunoepitopes and Development of Peptide-based Sarcoidosis Immunoassay. American Journal of Respiratory and Critical Care Medicine. doi.org/10.1164/rccm.202306-1054oc
Rheumatoid arthritis impacts approximately 2 million people in the United States and is associated with increased risk of cardiovascular disease. However, assessing cardiovascular risk is difficult in patients with rheumatoid arthritis because standard clinical assessments based on factors like age, cholesterol, and smoking status tend to underestimate cardiovascular risk in individuals with rheumatoid arthritis.
In a new study published in the Journal of the American Heart Association, a research team led by physicians at Mass General Brigham with expertise in rheumatology and cardiovascular disease identified six blood biomarkers that are associated with cardiovascular risk in patients with rheumatoid arthritis and whose measurements improved the researchers’ ability to predict a future increase in arterial inflammation. The biomarkers hold the potential to clinically assess an individual patient’s risk of cardiovascular disease, but more research is needed to determine whether they are associated with cardiovascular events such as heart attack or stroke.
We think these biomarkers might improve our ability to predict risk and intervene early to help our patients. The idea is that if we measure biomarkers that are specific to rheumatoid arthritis, we might be able to better identify those at highest risk of cardiovascular events.”
Daniel H. Solomon, MD, MPH, first author, chief of the Section of Clinical Sciences in the Division of Rheumatology and Matthew H. Liang Distinguished Chair at Brigham and Women’s Hospital, founding member of the Mass General Brigham healthcare system
To identify rheumatoid arthritis-specific biomarkers of cardiovascular risk, the researchers assembled a panel of 24 candidate biomarkers that had been previously shown to be associated with rheumatoid arthritis and systemic inflammation. Then, they measured the concentration of these biomarkers in 109 patients with rheumatoid arthritis who were taking part in a randomized clinical trial (the TARGET Trial) to compare the efficacy of two different treatments for rheumatoid arthritis at preventing cardiovascular disease. The researchers measured the biomarkers at the beginning of the study and six months later, imaging the patients’ arteries at each time to assess their arterial inflammation-;an indicator of cardiovascular risk.
“Arterial inflammation can predict future cardiovascular disease risk,” said cardiologist and co-author Ahmed Tawakol, MD, the director of Nuclear Cardiology and co-director of the Cardiovascular Imaging Research Center at Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system. “If you take a snapshot of a person’s blood vessels, the more inflammation that is measured there, the greater the likelihood the person will have progression of their disease, and the greater likelihood that they will have a stroke or a myocardial infarction.”
Six of the 24 biomarkers were associated with increased cardiovascular risk and using them in predictive models improved the researchers’ ability to predict increases in arterial inflammation compared to standard clinical indices such as the Framingham Risk Score, which is based on factors such as age, sex, cholesterol, blood pressure, diabetes, and smoking.
“This is an important step towards using blood samples to measure changes in cardiovascular risk with the treatment of rheumatoid arthritis,” said Solomon.
The study showcases the strength of ongoing collaborations between Brigham and Women’s Hospital and Massachusetts General Hospital, said Solomon and Tawakol, who trained together as residents at the Brigham around 30 years ago. “Having two really great institutions collaborating in the same organization meant we could leverage the strengths of the respective institutions and teams,” said Solomon.
Now, the team is working to test these biomarkers in a larger and more long-term cohort of rheumatoid arthritis patients, the Brigham and Women’s Rheumatoid Arthritis Sequential Study (BRASS), which has been following over 1,000 patients with rheumatoid arthritis since 2003. This follow-up study will allow the researchers to not only test associations between the biomarkers and arterial inflammation, but also assess whether the biomarkers can predict future cardiovascular events such as heart attack or stroke.
Source:
Journal reference:
Solomon, D. H., et al. (2024) Biomarkers of Cardiovascular Risk in Patients with Rheumatoid Arthritis: Results from the TARGET Trial. Journal of the American Heart Association. DOI: 10.1161/JAHA.123.032095.
Pharmaceutical companies that manufacture insulin made headlines last year when they voluntarily agreed to provide discount cards that lower the monthly cost of insulin for many people to $35.
But getting your hands on this card — and persuading a pharmacist to accept it — can be a hassle.
In this episode of “An Arm and a Leg,” producer Emily Pisacreta speaks with “insulin activists” and pharmaceutical experts to find out what this change in prices means for people with diabetes and why the fight for affordable insulin isn’t over yet.
Host and producer of “An Arm and a Leg.” Previously, Dan was a staff reporter for Marketplace and Chicago’s WBEZ. His work also appears on All Things Considered, Marketplace, the BBC, 99 Percent Invisible, and Reveal, from the Center for Investigative Reporting.
Note: “An Arm and a Leg” uses speech-recognition software to generate transcripts, which may contain errors. Please use the transcript as a tool but check the corresponding audio before quoting the podcast.
Dan: Hey there. Right after the holidays, I got an email from a listener named Brianna.It started, “Happy new year Dan! I was just reading the news about the price of insulin going down to $35! Is that for everyone?”
And I was like, Huh. I had a sense that there was some news about the price of insulin, but 35 dollars a month for everyone? That sounded like a BIG reduction. And big news.I googled the latest stories, and I was… not totally sure what I was seeing.
I was definitely seeing some new stories about people paying 35 bucks from here on out. And there seemed to be some federal law involved, and politicians were patting themselves on the back. But it just wasn’t totally clear: Was insulin now 35 dollars for everyone? Did the outrageous price of insulin get solved while I wasn’t looking?
And I mean, I’ve kinda been looking. We’ve done a couple of episodes about the price of insulin already — because insulin is iconic. It represents the wild cost of prescription drugs in this country. More than 8 million Americans take insulin to treat their diabetes – and for some, going without it could actually kill you.
And its price got jacked up so much — huge multiples over like ten years — — that one in four of those people who couldn’t go without… took to rationing: Seeing how much they could go without, short of actually dying.
So I asked our senior producer Emily Pisacreta to take the case.
Emily: I feel more like the senior insulin correspondent, which is fine with me as the resident type 1 diabetic! And a lot has happened since the last time we talked about insulin on this show. We really do need an update.
Dan: This is an “Arm and a Leg”, a show about why healthcare costs so freaking much, and what we can maybe do about it. I’m Dan Weissmann, I’m a reporter and I like a challenge. So our job here is to take one of the most enraging, terrifying, depressing parts of American life, and bring you something entertaining, empowering and useful.
Today we have a question: what’s going on with insulin? Is it $35 now?
Emily: Well, there have been some BIG improvements — bigger than I thought when I started reporting. A lot of people can get their monthly supply of insulin for just $35. But it is oversimplified to say it just costs $35 now. And the people who have been fighting to lower the price of insulin over the past decade? They’re still very pissed. So let me walk you through what changed, what led to those changes, and what’s still unresolved.
Dan: OK!
Emily: For years now, there’s been a giant push from people with diabetes to get the federal government to do something about the high cost of insulin. In 2022, finally something came through. I’m talking about a provision in Inflation Reduction Act.
Dan: Yes– I remember this– the Inflation Reduction Act was a big infrastructure bill that included, like renewable energy subsidies, and– honestly, this is the reason that I remember the bill, because we did an episode about this part– letting medicare negotiate some drug prices?
Emily: Exactly. It said people on Medicare would be able to get a month’s supply of insulin for no more than $35 out of pocket. But of course that left a big gaping hole. BECAUSE that’s cool for people on Medicare, but what about the rest of us? And the pharma companies were feeling the heat. Here’s President Biden in his State of the Union last year:
President Biden: Big pharma has been unfairly charging people hundreds of dollars, four to $500 a month making record profits. Not anymore. Not anymore.
Emily: By the way, those pharma companies? There’s three of them who make insulin.
That’s the American company Eli Lilly, the Danish company Novo Nordisk, and the French company Sanofi. OK so: not long after Joe Biden talked about their record profits, the insulin makers were back in the news. …
Eli Lilly was the first to announce they were going to slash prices on several of their most popular insulins, and limit out of pocket spending to $35 a month.
Fox News: This is a big story.
Next, Novo Nordisk and Sanofi made similar announcements.
CNN: Millions of Americans are affected by this major news this morning for millions of people suffering from diabetes and high prescription drug costs.
Basically, the insulin manufacturers all said hey, you’re not covered by this Medicare thing? We’re going to bring your copay down to $35 ourselves. So if you have commercial insurance Print out this card, take it to the pharmacy, and your copay will be no more than $35 for a month’s supply of insulin.
Dan: And what if you’re uninsured?
Emily: Well, they have a card for that, too.
Dan: OK so what I’m hearing is you need a card.
DAN: Yes. How do you get one?
Emily: The insulin makers set special phone numbers you can call. Or you can visit their websites, fill out a little form, and download the card.
Dan: Sounds simple, unless I’m missing something?
Emily: In all honesty, I had no problem with those steps. But I wouldn’t assume that’s the case for everyone. And I’m also not rationing insulin right now.
Zoe Witt: When you are rationing insulin, maybe you aren’t even fully rationing insulin yet, but you don’t know how you’re going to get Your next prescription, your next fill of insulin…You are in crisis. Like, you, you do not have the capability to sift through these websites. It’s very confusing. It’s very overwhelming.
Emily: This is someone who frequently speaks to people struggling to afford insulin.
Zoe Witt: my name is Zoe Witt. I work with Mutual Aid Diabetes.
Emily: Mutual Aid Diabetes. That’s an all volunteer group that has banded together to help diabetics get what they need, when they need it. They help people with cash and with free diabetes supplies, including insulin, no questions asked. That means Zoe knows the ins and outs of every obstacle to getting insulin.
Zoe Witt: Our healthcare system is like a whack a mole from hell.
Emily: And Zoe reminds me: if you’re not taking enough insulin, you probably feel awful. Maybe not even thinking straight. And it can affect your eyes, making it hard to read.
Zoe Witt: It just is unmanageable
Emily: Zoe says they talk with people all the time who are too stressed out or too debilitated to download these cards and use them. Diabetes folks walk people through the process. And once someone has the card… Mutual Aid Diabetes gives people the 35 bucks, too, if they say they need it. Because $35 can be a barrier for a lot of people. And it’s actually $70 sometimes if you use 2 types of insulin at once, which lots of people do… myself included.
Dan: Wow. OK. But then once people have the cards they typically have no problem?
Emily: Well, your pharmacist has to know what they’re doing, too. So sometimes it means a patient having to educate their pharmacist– or even bring the doctor in to help troubleshoot — which is no picnic. And people with diabetes are always having to deal with insurance roadblocks at the pharmacy, so I don’t want to make anything sound simpler than it is.
Dan: It’s like a whack a mole from hell!
Emily: Exactly! And the cards don’t solve everything. Especially this: if you have insurance, these cards only apply to the insulin your insurance plan already covers. If you normally need a prior authorization to get the right insulin for you… that is still the case.
Dan: Right. Okay. like prior authorization is this roadblock to getting all kinds of treatment, that you and your doctor agree that you should have, and your insurance company can say, we disagree. We’re s not authorizing this. And then you’re stuck.
Emily: Right.
Dan:But in terms of what the pharma companies. can do to kind of offer you a deal. They’re basically doing it. Is that right?
Emily: I think that’s fair to say.
Dan: That’s super interesting. All right. So it’s not solved, but this is a big step forward. And what’s not solved is: some people are still on the hook for the list price for insulin — the price without any discounts or insurance or whatever. But you found big improvements there too, right?
Emily: Yes! When the companies announced all these discount cards, they announced a whole other big change, too. Slashing the list prices of a bunch of different insulins by up 75%. So a vial that once was north of $300 is now being listed at around $70.
Dan: OK, that sounds like a big improvement.
Emily: It’s a big, big deal. Actual price reductions are what diabetes advocates have been demanding all along. And… while these are still the highest prices in the world for these same insulins, to see them drop from triple to double digits, it’s wild.
Dan: I sense that there’s a “but” here.
Emily: Well, the Big Three didn’t lower the price of every type of insulin, only ones that have been around since the 1990s or early 2000s. Newer insulins that work faster or last longer are not included here.
Dan: And I’m guessing not all insulins work the same way.
Emily: Right. Some people can switch between types or brands of insulin easily. For other people, there can be allergies or one works better with their body with another kind. It’s complicated. It’s medicine! AND… there have been some issues with pharmacies actually stocking lower list price insulin. That is a whole ‘nother saga… an episode for another day. But the important thing is… a bunch of insulin is a lot cheaper now.
Dan: Wow. Emily, you said right at the top: The changes here are bigger and better than you realized before you started reporting.
Emily: Yes but there’s still a lot more to say.
Right. After the break, we’ll’ hear from you about why these changes happened NOW. And what it means for people with diabetes and really all of us…
[midroll]
So. We have seen some big changes in the last year — including DRUG COMPANIES expanding their discount programs and lowering the sticker prices on insulin, dramatically. Why now? I’m guessing this wasn’t because they had a big change of heart.
Emily: I can’t speak to what’s in pharma’s hearts. But I did talk to someone who knows a lot about pharma’s brain.
Ed Silverman: my name is Ed Silverman, and I work at Stat News, a health and life sciences website,
Emily: I’m a big fan of Stat News
Dan: Me too, man! Their reporting is great.
Emily: And Ed Silverman. He’s been covering the pharmaceutical industry for almost 30 years. He thinks activism from people with diabetes over the years created political pressure that played a big role in the decision to slash prices. But there was also something kind of hidden at work.
Ed Silverman: It’s not altruism, here was a real mechanism, government mechanism in place that helped change the equation and therefore the thinking back at the companies.
Dan: OK… what is he talking about?
Emily: So, Dan: do you remember the stimulus bill, the American Rescue Plan?
Dan: I’m starting to feel like this episode is a quiz on recent-ish legislation. And I think I’m gonna do pretty well here:.The American Rescue Plan was a trillion dollar stimulus that Joe Biden got passed right after he got into office– am I right?
Emily: OK, hotshot. Do you remember how in part 8 section 9816 they sunsetted the limit on the maximum rebate for single source drugs and innovator multiple source drugs?
Dan: Um, busted. No.
Emily: Ok so here’s the deal: it’s obviously kinda wonky so I’ll simplify– in that little section Congress made a tweak to Medicaid, basically raising penalties on drug-makers for jacking up prices too far, too fast. So if you’re a pharma company who has raised the price of a drug by a lot very quickly, which is true of insulin, and a lot of people on Medicaid use your drug, which is also true of insulin, then you have to pay a big penalty. In the case of insulin, that penalty would be more than you’d make selling the insulin to Medicaid. A LOT more: So, unless you bring the price back down, you’re going to owe Medicaid a lot of moolah. And those penalties were set to kick in January 1st 2024.
Dan: So you’re telling me: Part of what the pharma companies did here came right out of a small part of a giant federal law from 2021.
Emily: Yep. And there’s another big wheel turning in the background here. Novo Nordisk and Eli Lilly, two companies who really got their start by selling insulin, now make other diabetes drugs — drugs that are now increasingly used for weight loss. And it’s a bonanza.
GMA: It is literally the hottest drug in the country right now.
Fox News: all people are talking about these days is Ozempic, wegovy. Oh my gosh, this person lost 20 pounds. This person lost 50 pounds.
Ozempic Ad: [Jingle:] “Oh, Oh, Oh, Ozempic!
[Announcer:] Once weekly Ozempic is helping many people with type 2 diabetes like James lower their blood sugar.
Emily: Drugs like Ozempic, Wegovy, Mounjaro. They’ve been in super high demand. And there’s been a ton of hype about their various potential health benefits. For weight loss, for heart health. Scientists are even interested in whether it can help people with substance use disorders. Meanwhile, for Eli Lilly and Novo Nordisk, the returns on these drugs dwarf anything else they’re selling. Novo Nordisk even became the biggest company in Europe – for like a minute… but still.
Dan: OK, this is interesting, but what does it have to do with the price of insulin?
Emily: I’d wondered… maybe these companies can just better afford to buy some political peace by lowering insulin prices, because they are making so much bank on these new drugs, ? Ed Silverman had a take on that.
Ed Silverman: It makes perfect sense that these cash cows, these medicines that are used for diabetes and, weight loss are going to become increasingly important to their bottom line more than other medicines
Emily: More than insulin. And they’re selling so much so fast, they can hardly keep up with demand. Which could end up affecting people who need insulin.
Dan: Wait, how?
Emily: Look, for example, in November, Novo Nordisk said they were investing 3 and half billion dollars into ramping up production of injection pens for Wegovy, one of their top drugs in this category. Less than a week later, Novo announced they would be phasing out one of their insulin products from the US market – an insulin called Levemir. It’s one of the insulins whose prices they just dropped. And… coincidence… Levemir also comes in a pen.
Dan: So Novo Nordisk is phasing out an insulin pen so they can make more Wegovy pens?
Emily: Well, we don’t know that for sure. But Novo Nordisk did tell me that “manufacturing constraints” were part of why they’re dumping Levimir. They said it was one of several reasons and also wrote: “We made this decision after careful consideration and are confident that given the advanced notice, U.S. patients will have access to alternative treatments and can transition to other options.
Dan: Huh. OK.
Emily: But even if pulling this insulin Levemir off the market had nothing to do with their trouble meeting the demand for their big blockbuster drug… it brings to mind an important question about all the changes we talked about today — whether it’s the copay savings or the lowered list prices. Here’s Ed Silverman.
Ed Silverman there’s no guarantee that the companies will keep these in place. Maybe after time, some of the attention on insulin is diverted and maybe eighteen months from now, one company might quietly roll back some of the Benefits, if you want to use that word, there’s nothing requiring them to maintain the steps they’ve taken.
Emily: I asked all three insulin makers about this. None of them promised there would never be any backsies. Lilly wrote back “Lilly is committed to ensuring all patients can access any Lilly medicine they need” — and touted their efforts to date. Similarly, Sanofi wrote “We continually review our affordability offerings to support our aim that no one should struggle to pay for their insulin. Novo Nordisk’s response was “Novo Nordisk increases the price of some of our medicines each year, in response to changes in the healthcare system, market conditions, and the impact of inflation.”
Dan: Yeah, that especially does not sound like a pinky-swear, no-backsies kind of response.
Emily: AND that’s not much comfort for insulin activists. Folks like Shaina Kasper, who works for T1International. They’re a group that’s been at the forefront of this fight for years. I Asked her…
Emily-on-tape: So is this issue of high insulin prices just resolved now?
Shaina Kasper: No, it hasn’t been. It’s been really frustrating…
Emily Shaina and others are worried that the announcements from the manufacturers about savings cards and voluntary list price reductions will take the pressure off the government to do something more sweeping. Because for now…
Shaina: The manufacturers really hold all of the power here And if patients are counting on these programs to literally be able to survive, that has life and death consequences
Dan: This question about who holds the power, it reminds me of a story we did a few months ago… the one about how the writer John Green led a kind of online crusade targeting the drug-maker Johnson & Johnson. And how, even though the pressure campaign worked — J & J ended up allowing lower-priced versions of an important tuberculosis drug — activists who worked on the issue were like: It’s a problem that Johnson & Johnson has the power to say yes or no here..
Emily: Exactly. That which pharma giveth, pharma can taketh. At least the way things are set up now. Now I should say, all three companies told me they plan to continue their affordability offerings. But if insulin continues to be the poster child for high drug prices, prices virtually everyone in America agrees are too high…it does raise the question: are voluntary programs from pharmaceutical companies the solution we want? To Zoe from Mutual Aid Diabetes, the answer is no. They find these manufacturer savings cards kind of a bitter pill… no pun intended.
Zoe Witt: there’s certainly no justice in these programs,
Emily: And zoe for one would say that justice is overdue.
Zoe Witt: These companies have price gouged us. for years, making obscene amounts of money. Then, presumably, as, we’re often told is the justification for these ridiculous prices, they did research and development for more diabetes drugs, which are Ozempic, Monjoro, etc. And now, these companies, for, the next 15 years, are set to make, billions and billions of dollars, on these drugs,
Emily: I asked the big three insulin manufacturers about what Zoe said – about how angry folks like them are over the cost of insulin. Novo Nordisk said “we continually review and revise our offerings as well as work with diverse stakeholders to create solutions for differing patient needs. ” And Sanofi and Lily both said something very similar.
Emily: So… in the end– or at least for now– here’s the answer to our listener’s question…. There are more avenues than ever to get a month’s supply of insulin for $35. Great. It may be a lot easier to avoid rationing your insulin now than it was a couple years ago. That’s also really great. But people with diabetes do not think this fight is over.
Dan: So what DO they want?
Emily: Some people still want the federal government to just put a cap on what people pay for insulin, like by law.. Others are working to build alternatives to the existing pharmaceutical industry, like California’s CalRx program.
Dan: Cal Rx… now you’re calling back our story from the last time we talked about insulin.
Emily: Yep, Cal Rx is the state of California’s attempt to enter the insulin market, to introduce some low priced generics and sell them essentially at cost. Other states are joining in. Even if some of these specific plans fall apart — even if California somehow can’t get its government-sponsored insulin to market, even if Pharma rolls back some of the discounts…the past few years have been enormous for people with diabetes. Mostly because they’ve found each other.
Zoe Witt: I was rationing insulin in 2018, I didn’t even know that there was a term for it. I didn’t know other people were doing it. I know a lot of people died that year. And there were multiple occasions where I, in retrospect, definitely almost died. And the one good thing that has, that has happened between now and then is that people have been talking about it and People are now more comfortable telling others that they’re struggling, that they can’t get their insulin.
Emily: Connecting with Mutual Aid Diabetes or other networks to get or give help.
Zoe Witt: We’re all keeping each other alive, like to me, that’s the number one thing that has changed.
Emily: I think that’s a huge lesson here, and a takeaway that’s not new on this show. Keeping each other alive — or even just keeping each other from getting bankrupted by the medical system — is up to us. And while a mutual aid group modeled exactly like Mutual Aid Diabetes may not work for every disease or every drug, Zoe says they’re more than willing to talk to anyone who might be interested in trying.
Zoe Witt: I mean, we’ve even had people ask, like, is there like a mutual aid asthma or something like for inhalers?
Emily: Their advice?
Zoe Witt: I think that, you know, to start, you would want, like, probably at least, like, five to ten “ride-or dies,” like, people that are really willing to, like, go the extra mile,
Dan: Five to ten– that just does not sound like that many! (I mean, I think.) One thing I’m taking away is: This is a lot of activism over a long time, that eventually had a big effect. Another thing I’m taking away here? Sneaky policy changes — like lifting the Medicaid rebate cap — can make a huge difference. God bless whatever nerds are writing the next little bit of law to sneak into a giant bill, like a hacker with a virus.
Emily: Totally. OK. I gotta take a shot, and eat my lunch.
Dan: Go for it. We’ll be back with a new episode in a few weeks. Till then, take care of yourself.
This episode of an arm and a leg was produced by Emily Pisacreta and me, Dan Weissman and edited by Ellen Weiss.
Adam Raymonda is our audio wizard. Our music is by Dave Weiner and blue dot sessions.
Gabrielle Healy is our managing editor for audience. She edits the first aid kit newsletter.
Bea Bosco is our consulting director of operations. Sarah Ballama is our operations manager.
And Arm and a Leg is produced in partnership with KFF Health News. That’s a national newsroom producing in depth journalism about healthcare in America and a core program at KFF, an independent source of health policy research, polling and journalism.
Zach Dyer is senior audio producer at KFF Health News. He’s editorial liaison to this show.
And thanks to the Institute for Nonprofit News for serving as our fiscal sponsor, allowing us to accept tax exempt donations. You can learn more about INN at INN. org.
Finally, thanks to everybody who supports this show financially– you can join in any time at arm and a leg show dot com, slash, support — and thanks for listening.
“An Arm and a Leg” is a co-production of KFF Health News and Public Road Productions.
In a recent review article published in the journal Nature Reviews Nephrology, researchers synthesized what is known about the long-term consequences of being chronically underhydrated.
Most people know hydration is vital to staying healthy, but surveys suggest that underhydration is a common problem affecting nearly half of surveyed adults in the United States and Europe. Experts believe it to be exacerbated by the lack of inclusion in health guidelines and reinforcement by doctors during preventive check-ups.
While the effects of acute dehydration in the short term are widely known, less clinical focus has been given to the long-term effects of chronic underhydration.
Epidemiological studies now suggest that even mild but chronic underhydration can lead to the development of coronary heart disease, heart failure, diabetes, obesity, kidney function deterioration, premature mortality, and faster aging. These findings have been strengthened by observing mice subjected to chronic water restriction.
Homeostasis is the state of balance among all the body systems needed for the body to survive and function correctly, and water balance is a key mechanism through which this happens. Osmoregulation, or the control of water and salt balance, is known to provide an osmotically stable environment for many cells.
Underhydration leads to adaptive changes across the body. At all times, water losses through respiration, the gastrointestinal tract, sweat, and urine must be matched by water gains through ingestion of food and liquids.
The body needs to maintain a stable composition and volume of intracellular fluids (ICF) and extracellular fluids (ECF); changes in the body’s water content, either because of a surplus or a deficit, affect all organs, tissues, and cells.
One response to a water balance deficit is the release of the antidiuretic hormone arginine vasopressin (AVP), which decreases water loss through excretion. Vasoconstriction, blood pressure stabilization, and increased heart rate occur while water reabsorption is facilitated.
The sensations of thirst and appetite for salt are also stimulated by AVP and angiotensin II (ANGII). However, thirst regulation or anticipatory inhibition operates to prevent overdrinking; thirst responses may also decline with age. Sweating is also attenuated, which can lead to compromised thermoregulatory responses in sweltering conditions and cause chronic kidney disease.
Over time, chronic underhydration may establish a new water balance steady state, matching water losses with water intake. This response may be triggered under conditions where access to water is limited. Over time, this could lead to the deterioration of physiological systems, but these mechanisms are poorly understood.
Diseases associated with underhydration
Researchers consider underhydration or hypohydration to be a moderate decrease in the body’s water levels that leads to water conservation mechanisms being activated so that normal levels of plasma osmolality and sodium can be maintained. This contrasts with dehydration, a state in which the water conservation mechanisms cannot maintain water balance.
Acute water loss is most visible in military personnel and athletes, increasing heart rate and reducing anaerobic exercise performance. Acute dehydration can also adversely affect cognitive functioning, including alertness, concentration, short-term memory, and visual perception.
Certain diseases and conditions are thought to predispose people to underhydration. For example, uncontrolled diabetes mellitus can lead to water loss because it reduces renal water reabsorption. Increased urine output can result from nephrogenic diabetes insipidus and some forms of polycystic kidney disease. Conversely, certain cancers and drugs can also stimulate AVP secretion without low water intake, leading to hyponatremia.
Interventions to increase hydration
In response to emerging evidence regarding the adverse effects of underhydration, researchers have begun to explore whether optimal hydration can prevent or slow metabolic and cardiovascular diseases.
Interventions that focused on regimens designed to increase water intake found that participants faced barriers such as forgetting to drink, lack of access, lack of thirst, dislike for the taste of water, and not appreciating the benefits of proper hydration; another issue was work-related disruptions resulting from an increased frequency of urination.
These challenges were demonstrated by an experiment that found lower adherence to water intake regimens compared to a control liquid of inactive syrup.
One trial that successfully increased hydration in the intervention group found that higher water intake was significantly associated with reduced copeptin levels among people with chronic kidney disease. Another found that the greatest changes were seen in people who were habitually low drinkers.
Conclusions
The literature identifies connections between chronic underhydration markers and a heightened risk of several chronic diseases, but the mechanisms underlying these phenomena are not well understood. There are indications that hydration could be a preventive tool, but causal inference has been limited by the lack of adherence to hydration regimens.
However, even with these limitations, there is evidence that optimal hydration can be beneficial for people who are habitually low drinkers. Future studies on the efficacy of interventions to increase water intake should monitor compliance more closely and continue to focus on chronically underhydrated populations who stand to gain the most.
