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Robert J. Freishtat working in the lab

Detecting early signs of type 2 diabetes through microRNA

Robert J. Freishtat working in the lab

Obesity is a major risk factor for insulin resistance and type 2 diabetes. Now researchers understand the pathogenesis better among teens with mid-level obesity, thanks to clues released from circulating adipocyte-derived exosomes.

Researchers know that exosomes, tiny nanoparticles released from fat cells, travel through the bloodstream and body, regulating a variety of processes, from growth and development to metabolism. The exosomes are important in lean, healthy individuals in maintaining homeostasis, but when fat gets ‘sick’ – the most common reason for this is too much weight gain – it can change its phenotype, becoming inflammatory, and disrupts how our organs function, from how our skeletal muscle and liver metabolize sugar to how our blood vessels process cholesterol.

Robert J. Freishtat, M.D., M.P.H., the chief of emergency medicine at Children’s National Health System and a professor of precision medicine and genomics at the George Washington University School of Medicine and Health Sciences, and Sheela N. Magge M.D., M.S.C.E., who is now the director of pediatric endocrinology and an associate professor of medicine at the Johns Hopkins School of Medicine, were curious about what this process looked like in teens who fell in the mid-range of obesity.

Obesity is a major risk factor for insulin resistance and type 2 diabetes, but Dr. Freishtat and Dr. Magge wanted to know: Why do some teens with obesity develop type 2 diabetes over others? Why are some teens in this mid-range of obesity metabolically healthy while others have metabolic syndrome? Can fat in obese people become sick and drive disease?

To test this, Dr. Freishtat and Dr. Magge worked with 55 obese adolescents, ages 12 to 17, as part of a study at Children’s National. The participants – 32 obese normoglycemic youth and 23 obese hyperglycemic youth – were similar in age, sex, race, pubertal stage, body mass index and overall fat mass. The distinguishing factor: The hyperglycemic study participants, the teens with elevated blood sugar, differed in where they stored fat. They had extra visceral fat (or adipose tissue) storage, the type of fat that surrounds the liver, pancreas and intestines, a known risk factor for type 2 diabetes.

Dr. Magge and Dr. Freishtat predicted that circulating exosomes from the teens with elevated blood sugar are enriched for microRNAs targeting carbohydrate metabolism.

They used three tests to examine study participants’ metabolism, body composition and circulating exosomes. The first test, an oral glucose tolerance test, measures how efficiently the body metabolizes sugar; the second test is the whole body DXA, or dual-energy x-ray absorptiometry, which analyzes body composition, including lean tissue, fat mass and bone mineral density; and the third test, the serum adipocyte-derived exosomal microRNA assays, is an analysis of circulating fat signals in the bloodstream.

They found that teens with elevated blood sugar and increased visceral fat had different circulating adipocyte-derived exosomes. These study participants’ exosomes were enriched for 14 microRNAs, targeting 1,304 mRNAs and corresponding to 179 canonical pathways – many of which are directly associated with carbohydrate metabolism and visceral fat.

Dr. Magge will present this research, entitled “Changes in Adipocyte-Derived Exosomal MicroRNAs May Play a Role in the Progression from Obese Normoglycemia to Hyperglycemia/Diabetes,” as an oral abstract at the American Diabetes Association’s 79th Scientific Sessions on Saturday, June 8.

Dr. Freishtat envisions having this information will be especially helpful for a patient in a mid-range of obesity. Exosomes primarily consist of small non-coding RNAs. In the current study, the altered RNAs affect P13K/AKT and STAT3 signaling, vital pathways for metabolic and immune function.

“Instead of waiting until someone has the biochemical changes associated with type 2 diabetes, such as hyperglycemia, hyperlipidemia and insulin resistance, we’re hoping physicians will use this information to work with patients earlier,” says Dr. Freishtat. “Through earlier detection, clinicians can intervene when fat shows sign of illness, as opposed to when the overt disease has occurred. This could be intervening with diet and lifestyle for an obese individual or intervening with medication earlier. The goal is to work with children and teens when their system is more plastic and responds better to intervention.”

As this research evolves, Dr. Freishtat continues to look at the intergenerational effects of circulating adipocyte-derived exosomes. Through ongoing NIH-funded research in India, he finds these exosomes, similar in size to lipoproteins, can travel across the placenta, affecting development of the fetus in utero.

“What we’re finding in our initial work is that these exosomes, or ‘sick’ fat, cross the placenta and affect fetal development,” Dr. Freishtat says. “Some of the things that we’re seeing are a change in body composition of the fetus to a more adipose phenotype. Some of our work in cell cultures shows changes in stem cell function and differentiation, but what’s even more interesting to us is that if the fetus is a female sex that means her ovaries are developing while she’s in utero, which means a mother’s adipocyte-derived exosomes could theoretically be affecting her grandchild’s phenotype – influencing the health of three generations.”

While this research is underway, Dr. Freishtat is working with JPOD @ Boston, co-located with the Cambridge Innovation Center in Cambridge, Massachusetts, to develop a test to provide analyses of adipocyte-derived exosomal microRNAs.

“It’s important for families to know that these studies are designed to help researchers and doctors better understand the development of disease in its earliest stages, but there’s no need for patients to wait for the completion of our studies,” says Dr. Freishtat. “Reaching and maintaining a healthy body weight and exercising are important things teens and families can do today to reduce their risk for obesity and diabetes.”

child measuring his stomach

Cognitive function does not predict weight-loss outcome for adolescents

child measuring his stomach

Though young people with intellectual disabilities or cognitive impairment have greater rates of obesity and other comorbidities that impact their health and well-being, primary care providers are often reluctant to discuss or refer these patients for weight-loss surgery due to concerns about their ability to assent to both the surgery and the ongoing diet and lifestyle changes after surgery.

However, a study in Pediatrics authored by psychologists at Children’s National Health System finds that these young people, including those with Down syndrome, have similar weight-loss trajectories to those with typical cognitive function after bariatric surgery. The study is the first to look at post-surgical outcomes for this subgroup of adolescent bariatric surgery patients.

“It’s challenging to ensure that an adolescent who is cognitively impaired understands what it means to undergo a surgical procedure like bariatric surgery, but we do find ways to ensure assent whenever possible, and make sure the patient also has a guardian capable of consent,” says Sarah Hornack, Ph.D., a clinical psychologist at Children’s National and the study’s first author. “A very important determinant of post-surgical success for any young candidate, however, is a support structure to help them with weight-loss surgery requirements. Often, we see that adolescents with lower cognitive function already have a well-established support system in place to assist them with other care needs, that can easily adapt to providing structure and follow through after weight-loss surgery, too.”

The study reviewed outcomes for 63 adolescents ranging in age from 13 to 24 years old with an average body mass index of 51.2, all of whom were part of the bariatric surgery program at Children’s National Health System. The participants were diagnosed with cognitive impairment or intellectual disability via standardized cognitive assessments as part of a preoperative psychological evaluation or through a previous diagnosis. This study adds to the body of research that is helping to create standard criteria for bariatric surgery in adolescents and teenagers.

Children’s National is one of only a few children’s hospitals with accreditation from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program of the American College of Surgeons and the American Society for Metabolic and Bariatric Surgery to offer bariatric surgery for adolescents with severe obesity. The extraordinary diversity of the patient population in Washington, D.C., including high rates of young people with obesity, allows the team to collect more comprehensive information about successful interventions across subgroups, including cognitive impairment or developmental disabilities, than nearly every other center in the United States.

“We’re happy to contribute evidence that can help families and care providers make informed health decisions for young people with intellectual disabilities or cognitive impairments. So many families are hoping to make sure that their children, despite disabilities, can be as healthy as possible in the long term,” says Eleanor Mackey, Ph.D., who is also a clinical psychologist at Children’s National and served as the study’s senior author. “Though the sample size is small, it does give credence to the idea that for many adolescents and teenagers, weight loss surgery may be a really viable option regardless of pre-existing conditions such as intellectual ability or cognitive function.”

Kofi Essel, M.D., M.P.H. and Ankoor Shah, M.D., M.B.A., M.P.H., named among 40 Under 40 Leaders in Minority Health

Ankoor Shah and Kofi Essel

Ankoor Shah, M.D., M.B.A., M.P.H., and Kofi Essel, M.D., M.P.H., were named 40 Under 40 Leaders in Minority Health.

Two doctors from Children’s National Health System are among the recipients of the 40 Under 40 Leaders in Minority Health award by the National Minority Quality Forum (NMQF) for 2019. Kofi Essel, M.D., M.P.H., is a pediatrician, Ankoor Shah, M.D., M.B.A., M.P.H., is the medical director of the IMPACT DC Asthma Clinic and also a pediatrician at Children’s National.

Founded in 1998, the NMFQ is dedicated to ensuring that high-risk racial and ethnic populations and communities receive optimal health care. The 40 individuals selected for this award represent the next generation of thought leaders in reducing health disparities.

Dr. Kofi Essel is a pediatrician at the Children’s Health Center Anacostia.  His focus and research has been around health equity, obesity, food insecurity and nutrition.

“Hunger strikes so many of our families,” says Dr. Essel, “In D.C., we were number one in the nation for having the highest rate of food hardship in households with children.”

Dr. Essel is involved with many organizations and initiatives that raise awareness about hunger and how much of an issue it is.  He strives to be a partner for the families that he serves, many of whom are in the fight against obesity, and works alongside them to improve their overall health.

“It’s a huge honor to receive recognition from this national organization,” says Dr. Kofi Essel, “Ultimately, it allows us to have a bit more of a platform to continue to advance some of the great work we’re doing with health disparities.”

Dr. Ankoor Shah is the medical director for IMPACT DC asthma clinic and a pediatrician at the Children’s Health Center at THEARC.  His focus includes improving pediatric population health and reducing child health asthma disparities.

“Through the coordination of the best in class care at Children’s National with amazing on the ground community partners, we have been able to transform the lives of the most at-risk children with asthma” says Dr. Shah.

Dr. Shah collaborates with organizations to improve the outcomes of kids with asthma by targeting intervention in high-risk areas.

“This award is recognition of the great work we’re doing in terms of improving asthma health in high-risk child populations throughout the District of Columbia.”

Both Dr. Essel and Dr. Shah are from Arkansas, attended Emory University and they did their residency together at Children’s National.

Congratulations to these wonderful doctors and leaders for receiving this award.

The 40 Under 40 recipients received their awards at the 2019 NMQF Leadership Summit on Health Disparities and CBC Spring Health Braintrust Gala Dinner on April 9.

Asha Moudgil examines a young patient

Preventing cardiovascular disease after pediatric kidney transplant

Asha Moudgil examines a young patient

Pediatric nephrologist Asha Moudgil, M.D. examines a kidney transplant patient.

As obesity has continued to rise among children in the U.S., so has a condition called metabolic syndrome – a constellation of factors, including high abdominal fat, insulin resistance, high blood pressure, high triglycerides and low amounts of high-density lipoprotein (“good” cholesterol), that increase future risk of cardiovascular disease.

Although metabolic syndrome is dangerous in otherwise healthy children, it’s particularly so for those who’ve received kidney transplants due to chronic kidney disease, says pediatric nephrologist Asha Moudgil, M.D., medical director of transplant at Children’s National Health System. Dr. Moudgil and Children’s National co-authors, Registered Dietitian Kristen Sgambat, Ph.D., RD, and Cardiologist Sarah Clauss, M.D., published a literature review in the February 2018 Clinical Kidney Journal outlining recent research about the cardiovascular effects of metabolic syndrome after kidney transplantation.

“Simply having this transplant multiplies the risk of cardiovascular disease in this vulnerable population,” Dr. Moudgil says. “Combined with lifestyle factors that are driving up metabolic syndrome in general, it’s a ‘one-two punch’ for these patients.”

Dr. Moudgil explains that chronic kidney disease itself leads to poor growth, resulting in shorter stature that’s a risk factor for developing increased waist-to-height ratio upon becoming overweight. When children with this condition undergo long-awaited transplants, it reverses some factors that were suppressing appetite and keeping weight in check: The chronically high levels of urea in their blood decrease after transplant, improving their appetites; and there’s no need to maintain the restrictive diets they had been required to follow for kidney health prior to transplant.

The pharmaceutical regimen that patients follow post-transplant often includes steroids that independently contribute to weight gain and insulin resistance. Combined with the typical American high-fat, high-sugar, and high-sodium diet and low levels of physical activity, the majority of patients with chronic kidney disease gain significant weight after they receive transplants. The prevalence of obesity doubles the first year after transplantation, from about 15 percent to 30 percent, not only driving up cardiovascular disease risk but endangering the longevity of their transplant.

At the same time, says Sgambat, risk factors before and after transplantation drive up prevalence of other parts of metabolic syndrome. These include hypertension, which affects the majority of patients with chronic kidney disease before transplant and typically worsens due to sodium and water retention from immunosuppressive drugs. Dyslipidemia, or abnormal lipid concentrations in the blood, is also common among pediatric kidney transplant patients. One study included in the review showed that 71 percent of patients had high triglycerides three months post-transplant.

Ethnicity also can drive up risk for metabolic syndrome and cardiovascular disease. For example, the literature review says, individuals of African descent have a higher risk of these two conditions potentially due to genetic factors, such as high risk apolipoprotein L1 gene variants.

Together, these factors spur production of inflammatory molecules that trigger the development of early cardiovascular disease. Many kidney transplant recipients die from cardiovascular complications in early adulthood, Sgambat says, driving the need for early detection.

To that end, Dr. Moudgil says pediatric patients don’t typically show overt abnormalities in standard measures of cardiac functioning, such as echocardiography. As an alternative, she and colleagues cover three tools in the literature review that could offer advanced insight into whether patients have initial signs of cardiovascular disease. One of these is carotid intima-media thickness, a measure of the thickness of the carotid artery that can be obtained noninvasively by ultrasound. Another is myocardial strain imaging by speckle tracking echocardiography, a global measure of how the heart changes shape while beating. Cardiac magnetic resonance imaging (MRI), a relatively new technique, is already showing promise in detecting signs of early cardiovascular dysfunction.

A far simpler way to gauge cardiovascular risk, Sgambat adds, is calculating patients’ waist-to-height ratio. This measure doesn’t require sophisticated tools and can be tracked in any clinic over time, alerting patients to health-altering changes before it’s too late.

“It’s even more important to treat cardiovascular risk factors aggressively in this population,” Sgambat says. “Getting a concrete measure that something is trending in the wrong direction may motivate patients to change their diet or lifestyle in ways that a simple recommendation may not.”

little girl in hosptial corridor

A growing list of factors that impact CKD severity for kids

little girl in hosptial corridor

Myriad biological and societal factors can impact the occurrence and accelerate progression of chronic kidney disease for children of African descent – including preterm birth, exposure to toxins during gestation and lower socioeconomic status – and can complicate these children’s access to effective treatments.

Myriad biological and societal factors can impact the occurrence and accelerate progression of chronic kidney disease (CKD) for children of African descent – including preterm birth, exposure to toxins during gestation and lower socioeconomic status – and can complicate these children’s access to effective treatments, according to an invited commentary published in the November 2018 edition of American Journal of Kidney Diseases.

Clinicians caring for “these vulnerable children should be mindful of these multiple competing and compounding issues as treatment options are being considered along the continuum from CKD to kidney failure to transplantation,” writes Marva Moxey-Mims, M.D., chief of the Division of Nephrology at Children’s National Health System.

The supplemental article was informed by lessons learned from The Chronic Kidney Disease in Children (CKiD) longitudinal study and conversations that occurred during the Frank M. Norfleet Forum for Advancement of Health, “African Americans and Kidney Disease in the 21st Century.”

African American children represent 23 percent of the overall population of kids with CKD in the CKiD study. While acquired kidney diseases can get their start during childhood when the diseases betray few symptoms, the full impact of illness may not be felt until adulthood. A number of factors can uniquely affect children of African descent, heightening risk for some kids who already are predisposed to suffering more severe symptoms. These include:

  • Preterm birth. African American children make up 36 percent of patients in CKiD with glomerular disease, which tends to have faster progression to end-stage renal disease. These diseases impair kidney function by weakening glomeruli, which impairs the kidneys’ ability to clean blood. Patients with a high-risk apolipoprotein L1 (APOL1) genotype already are at higher risk for focal segmental glomerulosclerosis (FSGS) and CKD. Researchers hypothesize that preterm birth may represent “a second hit that facilitates the development of glomerular damage resulting from the high-risk genotype.” According to the Centers for Disease Control and Prevention, 1 in 10 U.S. infants in 2016 was born preterm, e.g., prior to 37 weeks gestation.
  • APOL1 genotype. Compared with children who had a low-risk genotype and FSGS, children with a high-risk genotype had higher rates of uncontrolled hypertension, left ventricular hypertrophy, elevated C-reactive protein levels and obesity.
  • Human immunodeficiency viral (HIV) status. About 65 percent of U.S. children with HIV-1/AIDS are African American. In a recent nested case-control study of children infected with HIV in the womb, infants with high-risk APOL1 genotypes were 3.5 times more likely to develop CKD with viral infection serving as “a likely second hit.”
  • Access to kidney transplant. African American adults experience a faster transition to end-stage renal disease and are less likely to receive kidney transplants. African American children with CKD from nonglomerular diseases begin renal replacement therapy 1.6 years earlier than children of other races, after adjusting for socioeconomic status. Their wait for dialysis therapy was 37.5 percent shorter. However, these African American children waited 53.7 percent longer for transplants. Although donor blood types, genetic characteristics and other biological factors each play contributing roles, “these findings may reflect sociocultural and institutional differences not captured by socioeconomic status,” Dr. Moxey-Mims writes.

To alleviate future health care disparities, she suggests that additional research explore the impact of expanding services to pregnant women to lower their chances of giving birth prematurely; early childhood interventions to help boost children’s educational outcomes, future job prospects and income levels; expanded studies about the impact of environmental toxicities on prenatal and postnatal development; and heightened surveillance of preterm infants as they grow older to spot signs of kidney disease earlier to slow or prevent disease progression.

“Clinicians can now begin to take into account genetics, socioeconomic status and the impact of the built environment, rather than blaming people and assuming that their behavior alone brought on kidney disease,” Dr. Moxey-Mims adds. “Smoking, not eating properly and not exercising can certainly make people vulnerable to disease. However, there are so many factors that go into developing a disease that patients cannot control: You don’t control to whom you’re born, where you live or available resources where you live. These research projects will be useful to help us really get to the bottom of which factors we can impact and which things can’t we prevent but can strive to mitigate.”

The article covered in this post is part of a supplement that arose from the Frank M. Norfleet Forum for Advancement of Health: African Americans and Kidney Disease in the 21st Century, held March 24, 2017, in Memphis, Tennessee. The Forum and the publication of this supplement were funded by the Frank M. Norfleet Forum for Advancement of Health, the Community Foundation of Greater Memphis and the University of Tennessee Health Science Center.

Marva Moxey Mims

Making the case for a comprehensive national registry for pediatric CKD

Marva Moxey Mims

“It’s of utmost importance that we develop more sensitive ways to identify children who are at heightened risk for developing CKD.,” says Marva Moxey-Mims, M.D. “A growing body of evidence suggests that this includes children treated in pediatric intensive care units who sustained acute kidney injury, infants born preterm and low birth weight, and obese children.”

Even though chronic kidney disease (CKD) is a global epidemic that imperils cardiovascular health, impairs quality of life and heightens mortality, very little is known about how CKD uniquely impacts children and how kids may be spared from its more devastating effects.

That makes a study published in the November 2018 issue of the American Journal of Kidney Diseases all the more notable because it represents the largest population-based study of CKD prevalence in a nationally representative cohort of adolescents aged 12 to 18, Sun-Young Ahn, M.D., and Marva Moxey-Mims, M.D., of Children’s National Health System, write in a companion editorial published online Oct. 18, 2018.

In their invited commentary, “Chronic kidney disease in children: the importance of a national epidemiological study,” Drs. Ahn and Moxey-Mims point out that pediatric CKD can contribute to growth failure, developmental and neurocognitive defects and impaired cardiovascular health.

“Children who require renal-replacement therapy suffer mortality rates that are 30 times higher than children who don’t have end-stage renal disease,” adds Dr. Moxey-Mims, chief of the Division of Nephrology at Children’s National. “It’s of utmost importance that we develop more sensitive ways to identify children who are at heightened risk for developing CKD. A growing body of evidence suggests that this includes children treated in pediatric intensive care units who sustained acute kidney injury, infants born preterm and low birth weight, and obese children.”

At its early stages, pediatric CKD usually has few symptoms, and clinicians around the world lack validated biomarkers to spot the disease early, before it may become irreversible.

While national mass urine screening programs in Japan, Taiwan and Korea have demonstrated success in early detection of CKD, which enabled successful interventions, such an approach is not cost-effective for the U.S., Drs. Ahn and Moxey-Mims write.

According to the Centers for Disease Control and Prevention, 1 in 10 U.S. infants in 2016 was born preterm, prior to 37 weeks gestation. Because of that trend, the commentators advocate for “a concerted national effort” to track preterm and low birth weight newborns. (These infants are presumed to have lower nephron endowment, which increases their risk for developing end-stage kidney disease.)

“We need a comprehensive, national registry just for pediatric CKD, a database that represents the entire U.S. population that we could query to glean new insights about what improves kids’ lifespan and quality of life. With a large database of anonymized pediatric patient records we could, for example, assess the effectiveness of specific therapeutic interventions, such as angiotensin-converting enzyme inhibitors, in improving care and slowing CKD progression in kids,” Dr. Moxey-Mims adds.

Stephen Teach does an asthma exam

Stephen J. Teach, M.D., MPH, inaugural holder of new endowed chair

Stephen Teach does an asthma exam

Stephen J. Teach, M.D., M.P.H., has been named the inaugural Wendy Goldberg Professor in Translational Research in Child Health and Community Partnerships. This professorship comes with an endowed chair at Children’s National Health System.

The prestigious honor is given for the duration of Dr. Teach’s (and future chair holders’) employment at Children’s National. The award’s namesake, Wendy Goldberg, and her husband, Fred T. Goldberg Jr., are among the brightest stars in the constellation of Children’s National supporters, says Dr. Teach, Associate Dean for Pediatric Academic Affairs and Chair of the Department of Pediatrics at The George Washington University School of Medicine & Health Sciences.

In addition to serving on many Children’s boards, in the mid-2000s the Goldbergs made a $250,000 gift that benefited Improving Pediatric Asthma Care in the District of Columbia (IMPACT DC), Dr. Teach’s award-winning program to improve clinical care, empower patients and families, and conduct new research to improve patients’ outcomes.

“In recognition of the anchor aims of Children’s new strategic plan, the Goldbergs wanted this new gift to focus on the intersection of community health and research,” Dr. Teach says. “Thanks to their generosity, my team will work with community partners to use data to drive improvements in population health.”

With the dedicated funding Dr. Teach was able to hire a new staffer, Caitlin Munoz, to help mine electronic health records to create disease-specific registries that include 15,000 children and adolescents – the lion’s share of kids younger than 17 who live in Washington and have asthma.

“For the first time, we will be able to describe in granular detail the near-universe of local children who have this chronic respiratory disease,” he says. “We will be able to describe many of the most clinically meaningful aspects of nearly every child with asthma who lives in D.C., including mean age, gender, ethnicity and mean number visits to the emergency department.”

Such a richly textured database will help identify children who should be prescribed daily controller medications to help them avoid missing school days due to asthma exacerbations, he says. The next pediatric chronic disease they will track via registry will be pediatric obesity via elevated body mass index.

“That, in and of itself, is insightful data. But the enduring impact of this applied research is it will inform our continuous quality-improvement efforts,” he adds.

By querying the registries the team will be able to tell, for example, how Children’s primary care centers rank comparatively by asking such questions as which percentage of kids with asthma actually take the medicines they had been prescribed the year prior.

“Increasingly, clinical research falls into one of two buckets. You can either do better things: That’s discovering new drugs or processes, like our ongoing clinical trial to desensitize kids to asthma allergens. Or, you can do things better. We often know what to do already. We know that guideline-based asthma care works well. We don’t need to prove that again. We just need to do things better by getting this care to the kids who need it. That’s where this line of research/quality improvement comes in: It’s getting people to do things better.”

child measuring belly with tape measure

Children’s obesity research team presents compelling new findings

child measuring belly with tape measure

Faculty from Children’s National Health System’s Department of Psychology & Behavioral Health set out to learn if any demographic, psychiatric, or cognitive factors play a role in determining if an adolescent should be eligible for bariatric surgery, and what their weight loss outcomes might be. Presenting at the Society for Pediatric Psychology Annual Conference earlier this month, a group of researchers, fellows and clinicians, including surgeons from Children’s National showcased their findings. One of the posters developed by Meredith Rose, LGSW, ML, who works as an interventionist on a Children’s National clinical research team, received special recognition in the Obesity Special Interest Group category.

One presentation reported on a total of 222 pediatric patients with severe obesity, which is defined as 120 percent of the 95th percentile for Body Mass Index. Mean age of the participants was 16 years of age, 71 percent were female and 80 percent where Hispanic or non-White. As part of their preparation for surgery, all patients were required to complete a pre-bariatric surgery psychological evaluation, including a clinical interview and Schedule for Affective Disorders and Schizophrenia (KSADS-PL) screening. The studies by the Children’s teams were based on a medical record review of the pre-screening information. Adolescents being evaluated for surgery had high rates of mental health diagnoses, particularly anxiety and depression, but also included Attention Deficit Hyperactivity Disorder, eating disorders, and intellectual disability.

Another Children’s presentation at the conference looked at weight loss outcomes for adolescents based on IQ and intellectual disability. Overall, neither Full Scale IQ from the Wechsler Abbreviated Intelligence Scale – 2nd edition, nor the presence of an intellectual disability predicted weight loss following surgery.

“The sum of our research found that kids do really well with surgery,” said Eleanor Mackey, PhD, assistant professor of psychology and behavioral health. “Adolescents, regardless of the presence of intellectual disability areas are likely to lose a significant amount of weight following surgery,” added Dr. Mackey.

“This is a particularly important fact to note because many programs and insurers restrict weight loss surgery to ‘perfect’ candidates, while these data points demonstrate that our institution does not offer or deny surgery on the basis of any cognitive characteristics,” says Evan P. Nadler, M.D., associate professor of surgery and pediatrics. “Without giving these kids a chance with surgery, we know they face a lifetime of obesity, as no other intervention has shown to work long-term in this patient population. Our research should empower psychologists and physicians to feel more confident recommending bariatric surgery for children who have exhausted all other weight loss options.”

The research team concluded that examining how individual factors, such as intellectual disability, psychiatric diagnoses, and demographic factors are associated with the surgery process is essential to ensuring adequate and empirically supported guidelines for referral for, and provision of bariatric surgery in adolescents. Next steps by the team will include looking into additional indicators of health improvement, like glucose tolerance, quality of life, or other lab values, to continue evaluating the benefits of surgery for this population.

Adolescent brain scan from obesity study

Imaging captures obesity’s impact on the adolescent brain

Adolescent brain scan from obesity study

For the first time, a team of researchers led by Chandan Vaidya, Ph.D., chair of the Department of Psychology at Georgetown University, has used functional magnetic resonance imaging (fMRI) to capture the brain function of a small population of adolescents with obesity, both before and after bariatric surgery.

Obesity affects the whole body, from more obvious physical impacts on bones and joints to more subtle, internal impacts on organs like the brain.

For the first time, a team of researchers has used functional magnetic resonance imaging (fMRI) to capture the brain function of a small population of adolescents with obesity, both before and after bariatric surgery. The goal is to better understand the neural changes that occur when an adolescent is obese, and determine the effectiveness of interventions, such as vertical sleeve gastrectomy, at improving brain function as weight is lost.

The study, published as the November Editors’ Choice in the journal Obesity, found that executive and reward-related brain functions of study participants with obesity improved following the surgical procedure and initial weight loss.

How bariatric surgery changes the teenage brain from Research Square on Vimeo.

“We’ve known for some time that severe obesity has negative consequences on some neurocognitive function areas for adults,” says Chandan Vaidya, Ph.D., chair of the Department of Psychology at Georgetown University and a senior author of the study. “But for the first time, we’ve captured fMRI evidence in young patients, and also shown that surgical intervention and the resulting weight loss can reverse some of those deficits.”

“For me, this early evidence makes a strong case that when kids are struggling with severe obesity, we need to consider surgical intervention as an option sooner in the process,” notes Evan Nadler, M.D., director of the Bariatric Surgery Program at Children’s National Health System, who also contributed to the study. “The question that remains is whether the neurocognitive function improves more if surgery, and thus weight loss, happens earlier – and is there a time factor that should help us determine when to perform a procedure that will maximize improvements?”

The preliminary study included 36 participants and was conducted using patients recruited from the Children’s National Bariatric Surgery program, one of the first children’s hospitals to achieve national accreditation by the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program.

“We asked these questions because we know that in the kids we see, their behavioral, brain, and physical health are all very closely related to one another and have an impact on each other,” adds Eleanor Mackey, Ph.D., study senior author and co-principal investigator on the National Institute of Diabetes and Digestive and Kidney Diseases grant that funded the project. “We expected that as physical health improves, we might see corresponding improvements in brain and behavior such as cognitive and school performance.”

The study also pointed out some technical and practical challenges to studying this particular young population. Anyone with a BMI greater than 50 was not able to fit within the MR bore used in the study, preventing fMRI participation by those patients.

“In addition to future studies with a larger sample size, we’d like to see if there are neuroimaging markers of plasticity differences in a population with BMI greater than 50,” says Dr. Vaidya. “Does the severity of the obesity change how quickly the brain can adapt following surgery and weight loss?”

The abstract was selected by the journal’s editors as one that provides insights into preventing and treating obesity. It was featured at the Obesity Journal Symposium during Obesity Week 2017 in Washington, D.C., as part of the Obesity Week recognition, and a digital video abstract was also released about the findings.

child measuring belly with tape measure

Defining cardiovascular disease and diabetes risks in kids

child measuring belly with tape measure

In the Clinical Report, a study team describes the current state of play and offers evidence-based recommendations to guide clinicians on how to approach metabolic syndrome in children and adolescents.

For more than a decade and a half, researchers and clinicians have used the term “metabolic syndrome” (MetS) to describe a set of symptoms that can raise the risk of cardiovascular disease. Although this constellation of factors has proven to be a good predictor of cardiometabolic risk in adults, it has not been as useful for children. That’s why the American Academy of Pediatrics (AAP) now recommends that pediatricians instead focus on clusters of cardiometabolic risk factors that are associated with obesity, a condition that currently affects one in six U.S. children and adolescents.

In a new collaborative report, a study team from Children’s National Health System’s Division of Endocrinology and Diabetes, Harvard Medical School and Duke Children’s Hospital and Health Center describes the current state of play and offers evidence-based recommendations to guide clinicians on how to approach MetS in children and adolescents.

Adults with MetS have at least three of the following five individual risk factors:

  • High blood sugar (hyperglycemia)
  • Increased waist circumference (central adiposity)
  • Elevated triglycerides
  • Decreased high-density lipoprotein cholesterol (HDL-C), so-called “good” cholesterol and
  • Elevated blood pressure (hypertension).

This toxic combination ups adults’ odds of developing diabetes or heart disease. The process is set in motion by insulin resistance. Think Mousetrap, with each new development facilitating the next worrisome step. As fat expands, the cells become enlarged and become more resistant to insulin – a hormone that normally helps cells absorb glucose, an energy source. However, insulin retains the ability to stimulate fatty acids, which promotes even more fat cell expansion. Ectopic fat ends up stored in unexpected places, such as the liver. To top it off, the increased fat deposits end up causing increased inflammation in the system.

At least five health entities, including the World Health Organization, introduced clinical criteria to define MetS among adults, the study authors write. Although more than 40 varying definitions have been used for kids, there is no clear consensus whether to use a MetS definition for children at all, especially as adolescents mature into adulthood. Depending on the study, at least 50 percent of kids no longer meet the diagnostic criteria weeks or years after diagnosis.

“Given the absence of a consensus on the definition of MetS, the unstable nature of MetS and the lack of clarity about the predictive value of MetS for future health in pediatric populations, pediatricians are rightly confused about MetS,” the study authors write.

As a first step to lowering their patients’ cardiometabolic risks, pediatricians should prevent and treat obesity among children and adolescents, the study authors write. Each year, clinicians should perform annual obesity screening using body mass index (BMI) as a measure, and also should screen children once a year for elevated blood pressure. Nonfasting non-HDL-C or fasting lipid screening should be done for children aged 9 to 11 to identify kids whose cholesterol levels are out of line. The team also recommends screening for abnormal glucose tolerance and Type 2 diabetes in youth with BMI greater than or equal to the 85th percentile, 10 years or older (or pubertal), with two additional risk factors, such as family history, high-risk race/ethnicity, hypertension or a mother with gestational diabetes.

Pediatricians do not need to use cut points based on MetS definitions since, for many risk factors, the growing child’s risk lies along a continuum.

Treatments can include lifestyle modifications – such as adopting a negative energy balance diet, drinking water instead of sugar-sweetened beverages, participating in a moderate- to high-intensity weight-loss program, increasing physical activity and behavioral counseling.

“Identifying children with multiple cardiometabolic risk factors will enable pediatricians to target the most intensive interventions to patients who have the greatest need for risk reduction and who have the greatest potential to experience benefits from such personalized medicine,” the study authors conclude.

Fat Cells

Cellular signals may increase atherosclerosis risk

Fat Cells

Fat cells from obese patients have the ability to send signals that can accelerate biological processes leading to atherosclerosis.

Obesity has been linked to a variety of adverse health conditions, including Type 2 diabetes, cancer, heart attack and stroke – conditions that may begin as early as childhood in patients whose obesity also begins early. While this much is known, it has been unclear how extra fat mass might lead to these chronic health conditions.

New research from Children’s National Health System scientists might help answer this question. In findings presented at the 2017 annual meeting of the Pediatric Academic Societies, the research team shows that exosomes – nanosized chemical messages that cells send to each other to regulate protein production – isolated from very obese teenage patients behave very differently from those derived from lean patients and could be key players in heightening the risk of developing atherosclerosis. This hardening of the arteries can, in turn, increase the risk of heart disease and stroke in adulthood.

A research team led by Robert J. Freishtat, M.D., M.P.H., chief of emergency medicine at Children’s National, is exploring possible links between extra belly fat and obesity-related diseases, such as atherosclerosis, a buildup of plaque in arteries that can harden and restrict blood flow. More precise knowledge of the mechanisms by which obesity ratchets up heart risks holds the promise of helping the next generation of kids avoid experiencing chronic disease.

The working theory is that exosomes derived from belly fat from obese patients have the distinct ability to accelerate biological processes leading to atherosclerosis.

The research team isolated exosomes from five obese teenagers and compared them to five sex-matched lean adolescents. It turns out that exosomes derived from fat pick up their marching orders from microRNA content likely to target cholesterol efflux genes, which help reduce cholesterol buildup in cells.

The research team looked at differences in cholesterol efflux gene expression in THP-1 macrophages. Uptake of low-density lipoprotein cholesterol, “bad” cholesterol, was 92 percent higher than in those exposed to exosomes from obese patients compared with their lean counterparts. Exposure to obese exosomes also reduced cholesterol efflux.

“Atherogenic properties of fat-cell derived exosomes from obese patients differ markedly from the non-atherogenic profile of exosomes from lean patients. It is especially concerning that we see biological clues of heightened risk in teenagers, and the finding underscores how the seeds for atherosclerosis can be planted very early in life,” Dr. Freishtat says.

The presentation is the latest finding from a research team that, over years of work, is unraveling the mechanisms of cellular signaling by fat cells.  By closely examining very obese children – who have the most severe cardiometabolic disease – the team identified strong molecular signals of disease risk that they can search for in leaner patients who may be at risk for disease years from now.

“We know that morbidly obese patients have cardiovascular issues,” explains Dr. Freishtat. “An unanswered question is for patients with no clinical symptoms who are a little overweight. Can we look at them and say whether they are at risk for developing atherosclerosis, insulin resistance or Type 2 diabetes five or 10 years down the line? That’s the whole rationale for doing this work.”

The critical issue is what exosomes are up to. Dr. Freishtat says in lean people, they’re active and are very important in maintaining stable metabolism and homeostatic processes.

“When a person becomes obese, however, exosomes evolve,” he says. “They no longer support insulin signaling, which is helpful, and drive processes in the reverse direction, repressing insulin signaling – which can be harmful,” he adds.

Ultimately, the research team aims to revolutionize how chronic diseases like Type 2 diabetes are diagnosed. For far too long, clinicians have relied on symptoms like high glucose levels and excess urination to diagnose diabetes.

“By the time you have symptoms, it’s too late,” says Dr. Freishtat. “In many cases, damage has been done by relentless exposure to high sugar levels. The biological processes that underlie the Type 2 diabetes process began five, 10, 15 years earlier. If we can detect it earlier, before symptoms arise, intervention is going to have a more significant impact on improving and extending patients’ lives.”

Teen Girl drawing a heart on an iPad

Illuminating cardiometabolic risk in Down syndrome

Teen Girl drawing a heart on an iPad

A leading researcher at Children’s National says researchers should look closely at the increased risks of obesity and thyroid disease common in patients with Down Syndrome, and determine how these long term comorbidities relate to cardiovascular and metabolic (cardiometabolic) risk, body image, and quality of life.

Over the last several decades, physicians’ improved ability to treat the common comorbidities of Down syndrome, such as congenital heart disease, has dramatically prolonged survival. Today, more than 400,000 people across the country are living with Down syndrome, and life expectancy has increased to 60 years.

New strategies to manage care for patients with Down syndrome must include preventive, evidence-based approaches to address the unique needs of these patients, according to Sheela N. Magge, M.D., M.S.C.E., Director of Research in the Division of Endocrinology and Diabetes at Children’s. She says that these efforts should include looking more closely at the increased risks of obesity and thyroid disease common in this population, and determining how these long term comorbidities relate to cardiovascular and metabolic (cardiometabolic) risk, body image, and quality of life.

An NIH-funded study from Children’s National and the Children’s Hospital of Philadelphia (CHOP), led by Dr. Magge and her colleague from CHOP, Dr. Andrea Kelly, seeks to better understand how the body composition of patients with Down syndrome impacts their likelihood for developing diabetes and obesity-related cardiovascular risks long term.

“We know that individuals with Down syndrome are at increased risk for obesity, but what hasn’t been clear is whether or not they also have the same cardiometabolic risk associated with obesity that we know holds true for other populations,” says Dr. Magge. “In this previously under-studied population, the common assumption based on very limited studies from the 1970’s was that individuals with Down syndrome were protected from the diabetes and cardiovascular risks that can develop in other overweight people. However, more recent epidemiologic studies contradict those early findings.”

The study has enrolled 150 Down syndrome patients and almost 100 controls to date, and the team is currently beginning to analyze the data. Dr. Magge believes that the findings from this study will help to provide new, research-driven evidence to inform the long term clinical management of obesity and cardiometabolic risk in adolescents with Down syndrome.

She concludes, “The goal is for our research to provide the foundation that will advance prevention and treatment strategies for this understudied group, so that individuals with Down syndrome not only have a longer life expectancy, but also a healthier and better quality of life.”

Scientist with centrifuge

Giving fat cell messages a positive spin

Woman on a scale

Study findings offer hope to the nearly 2 billion adults who are overweight or obese worldwide that detrimental effects of carrying too much weight can recede. (Image source: Centers for Disease Control and Prevention)

Losing weight appears to reset the chemical messages that fat cells send to other parts of the body that otherwise would encourage the development of Type 2 diabetes, substantially reducing the risk of that disease, a team led by Children’s National Health System researchers report in a new study. The findings offer hope to the nearly 2 billion adults who are overweight or obese worldwide that many of the detrimental effects of carrying too much weight can recede, even on the molecular level, once they lose weight.

In 2015, Robert J. Freishtat, M.D., M.P.H., Chief of Emergency Medicine at Children’s National and Associate Professor of Pediatrics, Emergency Medicine and Integrative Systems Biology at The George Washington University School of Medicine & Health Sciences, and colleagues showed that fat cells (also known as adipocytes) from people who are obese send messages to other cells that worsen metabolic function. These messages are in the form of exosomes, nanosized blobs whose contents regulate which proteins are produced by genes. Exosomes are like “biological tweets,” Dr. Freishtat explains — short signals designed to travel long distances throughout the body.

Dr. Freishtat’s earlier research showed that the messages contained in exosomes from patients who are obese alter how the body processes insulin, setting the stage for Type 2 diabetes. However, says Dr. Freishtat, it has remained unclear since that publication whether these aberrant messages from adipocytes improve after weight loss.

“We’ve known for a long time that too much adipose tissue is bad for you, but it’s all moot if you lose the weight and it’s still bad for you,” he explains. “We wanted to know whether these negative changes are reversible. If you reduce fat, does the disease risk that goes along with excess fat also go away?”

Details of the study

To investigate this question, Dr. Freishtat and colleagues worked with six African American adults scheduled to receive gastric bypass surgery — a nearly surefire way to quickly lose a large amount of weight. The volunteers, whose average age was 38 years, started out with an average body mass index (BMI) of 51.2 kg/m2. (The Centers for Disease Control and Prevention considers a healthy BMI to range between 18.5 to 24.9.)

Two weeks before these volunteers underwent surgery, researchers collected blood samples and took a variety of measurements. The researchers then performed a repeat blood draw and measurements one year after the surgery took place, when the volunteers’ average BMI had dropped to 32.6.

Dr. Freishtat and colleagues drew out the adipocyte-derived exosomes from both sets of blood samples and analyzed their contents. The team reports in the January 2017 issue of Obesity that at least 168 microRNAs — the molecules responsible for sending specific messages — had changed before and after surgery. Further analyses showed that many of these microRNAs were involved in insulin signaling, the pathways that the body uses to regulate blood sugar. By changing these outgoing microRNAs for the better, Dr. Freishtat says, adipocytes actively were encouraging higher insulin sensitivity in other cells, warding off Type 2 diabetes.

Sure enough, each volunteer had better insulin sensitivity and other improved markers of metabolic health post-surgery, including lower branched chain amino acids and a two-fold reduction in their glutamate to glutamine ratio.

“These volunteers were essentially cured of their diabetes after surgery. The changes we saw in their surgery-responsive microRNAS correlated with the changes we saw in their metabolic health,” Dr. Freishtat says.

A glimpse into the future

Dr. Freishtat and colleagues plan to study this phenomenon in other types of weight loss, including the slower and steadier paths that most individuals take, such as improving diet and doing more exercise. The team expects to see similar changes in exosomes of patients who lose weight in non-surgical ways.

By further examining the aberrant messages in microRNAs being sent out from adipocytes, he says, researchers eventually might be able to develop treatments to reverse metabolic problems in overweight and obese patients before they lose the weight, improving their health even before the often challenging process of weight loss begins.

“Then, if you can disrupt this harmful signaling in combination with weight-loss strategies,” Dr. Freishtat says, “you’re really getting the best of both worlds.”

Eventually, he adds, tests might be available so that doctors can warn patients that their fat cells are sending out harmful messages before disease symptoms start. By giving patients an early heads up, Dr. Freishtat says, patients might be more likely to heed advice from physicians and make changes before it’s too late.

“If doctors could warn patients that their fat is telling their blood vessels to fill up with plaque and trigger a heart attack in 10 to 20 years,” he says, “patients might be more compliant with treatment regimens.”

Drug dosing guidelines poor fit for obese patients

Children’s National researchers are among the top teams examining how obesity alters pharmacokinetics and the effect of body mass index on drug dosing and treatment outcomes specifically for pediatric and adolescent patients.

Obesity affects about 12.7 million U.S. children and adolescents – or about 1 in 6 kids across the nation, according to the Centers for Disease Control and Prevention. Despite this, there is a significant dearth of dosing guidelines for practitioners, for example pediatric anesthesiologists, to follow when administering potent anesthetics to pediatric patients who are obese.

Janelle D. Vaughns, M.D., director of bariatric anesthesia within the Division of Anesthesiology, Pain and Perioperative Medicine, says Children’s National Health System sees pediatric and adolescent patients of extreme weight (as much as 450 pounds) presenting for weight-loss surgery. In order to ensure that patients remain anesthetized during their surgical procedures, anesthesiologists use various classes of drugs, including hypnotics, muscle relaxants and pain medications. Dr. Vaughns says providers across the nation face similar challenges when determining accurate and precise dosing of drugs for obese pediatric patients.

“Medical guidelines calibrated for a 13-year-old of typical weight cannot be applied to a 13-year-old who weighs 400 pounds. Because morbid obesity in kids is a relatively new phenomenon in our country and globally, there are no formal guidelines to aid with dosing. In this scenario, most doctors extrapolate from guidelines written for lean patients. Because anesthetic drugs are so strong, it is essential to use the correct dose in all patients,” she says.

A recent brief report that Dr. Vaughns co-authored examines this issue. Researchers at Children’s National and the Washington Hospital Center conducted a retrospective review for 440 adult patients who received rapid sequence endotracheal intubation (RSI) in an urban, tertiary care academic Emergency Department. The patients received succinylcholine (a muscle relaxant) and etomidate (a short-acting anesthetic), whose doses are ideally calculated in milligrams per kilogram of total body weight.

The work, published in the December 2016 issue of American Journal of Emergency Medicine, reinforced the importance of data-driven guidelines for all patients. The research team found that the 129 obese patients included in the study were more likely to receive too little of the studied drugs while the 311 non-obese patients studied were more likely to receive too much medicine.

“Our single-center study demonstrates that obesity is a significant risk factor for underdosing RSI medications, whereas non-obesity is a risk factor for overdosing of these medications,” the research team concludes. This study also was reviewed and featured by the New England Journal of Medicine “Journal Watch” in October 2016.

Broadly, the issue of dosing potent medicines for pediatric obese patients is a national public health concern, Dr. Vaughns says. Research teams across the nation have made a concerted effort to publish papers on topics such as how obesity alters pharmacokinetics – how the body takes up, distributes and disposes of powerful medicines – and the deleterious effect of unhealthy body mass index on treatment outcomes for children with diseases such as acute myeloid leukemia.

Dr. Vaughns is among the clinician researchers working with the Pediatric Trials Network (PTN), sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, to fill this research gap. Working as a team, she, Evan Nadler, M.D., a bariatric surgeon, and Johannes N. van den Anker, M.D., Ph.D., division chief of Clinical Pharmacology, enroll pediatric patients in ongoing trials with a special focus on surgical patients who are obese.

The network is currently conducting pediatric studies at a number of locations, including Children’s National, leveraging blood samples and other specimens drawn during regular care to better understand how medicines routinely used in pediatric patients actually work in kids and to determine appropriate dosing.

Ultimately, the information PTN researchers discover from their multi-year studies will help the Food and Drug Administration update medicine labels to reflect safer, more accurate and more effective dosing for all pediatric patients.

Robert J. Freishtat

A game changer for detecting complications from obesity

Robert J. Freishtat

The work that Children’s National Health System physician-scientist Robert J. Freishtat, M.D., M.P.H., and colleagues are doing could soon be a game changer when it comes to early intervention and prevention of obesity-related illnesses.

They already knew there’s a direct relationship between the amount of visceral adipose, or belly fat, a person has and development of some of the most common and life-threatening complications of obesity, including cardiovascular disease and the insulin resistance that leads to diabetes. What remained unclear, until recently, were the precise mechanisms for how the increase in belly fat triggers the onset of additional disease.

Dr. Freishtat, senior author of “Adipocyte-Derived Exosomal miRNAs: A Novel Mechanism for Obesity-Related Disease,” published by Pediatric Research, studies the adipocytes, or fat cells, of visceral adipose in both lean and obese patients to understand exactly how these fat cells can and do wreak havoc — not just locally but throughout the body. Cells leverage exosomes to communicate among themselves, but in overweight patients those cellular communications can go awry.

“As the body’s visceral fat grows, somewhere on the path to obesity the fat cells change and begin to release different exosomes than lean adipose cells do. These new messages disrupt some important processes that eventually prevent the body from effectively dealing with sugar and cholesterol,” says Dr. Freishtat, chief of Emergency Medicine at Children’s National, and associate professor of Pediatrics, Emergency Medicine, and Integrative Systems Biology at the George Washington University.

Dr. Freishtat describes exosomes as “biological tweets”— short messages shed by all cells that allow for intercellular communication and alter gene expression. In the case of the adipocytes that exist in large quantities of visceral fat, these “tweets” actually cause the downregulation of proteins impacting two key signaling pathways — TGF-β and Wnt/β-catenin — associated with controlling chronic inflammation and fibrotic disease throughout the body. These signaling changes make morbidly obese patients more vulnerable to systemwide issues, such as cholesterol accumulation and changes to how the liver processes fat.

Details of the study

The study authors surgically collected fat tissue from lean and obese female patients aged 11 to 19 and used modified bead-based flow cytometry to separate, identify, and compare the exosomal RNA shed by the fat cells in both lean and obese samples. To confirm the unique impact of the obese adipose exosomes on gene expression, the research team then exposed lung cells in vivo to the exosomes shed by both lean and obese adipose. They measured the impact of exposure and uptake on a single receptor type — activin receptor type-2B — known to have a major influence on the TGF-β pathway. The exosomes from obese adipose caused the receptor to slow down, leading to significant changes in the function of the TGF-β pathway.

The team continues to explore how the exosomes shed from excess amounts of visceral adipose spread throughout the body and how the function of organs such as the liver, the heart, and the brain are impacted by the migrating fat cells.

A Look into the future

Successfully identifying and isolating these exosomes also has opened the door to developing a test to detect them, an idea that may permit even earlier intervention to delay or prevent the onset of obesity-related illnesses.

“It is entirely plausible, and is on its way to happening very soon, that someone could walk into their physician’s office for a routine physical and, via a urine test, find out that they are on the road to some dangerous additional side effects of significant weight gain,” says Dr. Freishtat. “That type of early detection could really be a game changer for the millions of Americans who are on track to developing heart, liver, and other diseases resulting from morbid obesity.”