A Large-Scale Study Finds Genes Linked to Obesity

Mar 6, 2018 | Featured, Research

Ruth Loos, PhD

Diet and physical activity are not the only factors that determine how easily a person gains or loses weight. A recent study led by researchers at the Icahn School of Medicine at Mount Sinai and other institutions of the Genetic Investigation of ANthropometric Traits (GIANT) consortium has found that 13 genes may play an important role, as well.

According to the study, published in the January 2018 issue of Nature Genetics, these 13 genes carry variations associated with body mass index (BMI).

“Our study has identified genes that play a crucial role in the neuronal control of body weight,” says lead researcher Ruth Loos, PhD, Professor of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai, and Director of the Genetics of Obesity and Related Metabolic Traits Program at The Charles Bronfman Institute for Personalized Medicine. “They act in the brain in pathways that may affect people’s food intake, hunger, and satiety. Individuals who inherit these genetic variations may find it harder to eat less or stop eating, compared to those who did not inherit these variations.”

The study, led by Dr. Loos and Joel Hirschhorn, MD, PhD, Concordia Professor of Pediatrics and Professor of Genetics at Boston Children’s Hospital and Harvard Medical School, and Co-director of the Broad Institute Metabolism Program, also involved the collaboration of more than 250 international research institutions that comprise the GIANT consortium.

In the past decade, researchers in the GIANT consortium have performed genome-wide screens in hundreds of thousands of individuals to identify genetic variations associated with obesity and BMI. In this new study, the consortium focused on a specific set of genetic variations that are likely to affect the function of genes and their proteins—an approach that expedited the discovery of the causal genes that affect body weight.

Genetic data from more than 700,000 individuals and 125 different studies were combined to form the largest genetic association study to date. The researchers identified a total of 14 genetic variations in 13 genes, including a “stop” variation in a gene called MC4R that causes carriers to weigh 15 pounds more, on average, than individuals who do not carry the “stop” variation.

Genes contain the information needed to make proteins. In the case of a “stop” variation, the translation from gene to protein is halted, and the protein is shorter than normal. About 1 in 5,000 individuals carries the “stop” variant in MC4R, which causes the gene not to produce the protein needed to inform the brain to stop eating. While this variant was identified two decades ago in individuals with extreme and early onset obesity, the new study shows that it also affects body weight in the general population.

Eight of the 13 genes identified were newly implicated in obesity and will require further follow-up to understand the mechanisms through which they affect body weight. By knowing the genes and the biological pathways through which they work, researchers believe they are a few steps closer to understanding why some people gain weight more easily than others, which is critical for developing effective treatments.

Genes are not the only factor in determining body weight, and it is important to be physically active and maintain a healthy diet, Dr. Loos says. However, she says, “Our study has provided new potential targets for therapeutic interventions, and may even help personalize treatment for carriers of the genetic variations.”

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Remote Monitoring Improves Readmission Rates for Heart Failure Patients

Mar 6, 2018 | Featured, Research, Your Health

Sean P. Pinney, MD

Mount Sinai Heart is reducing readmissions and improving quality of life for congestive heart failure (CHF) patients with remote monitoring using new devices and apps, as well as old-fashioned compassionate care.

“We are creating a multimodal way of keeping an eye on our patients after they have left the hospital so that we can optimize their medications and keep them at home—where they want to be—rather than in the hospital,” says Sean P. Pinney, MD, Professor of Medicine (Cardiology), Icahn School of Medicine at Mount Sinai, and Director of Heart Failure and Transplantation, Mount Sinai Health System.

One of the strategies involves the ReDS™ (Remote Dielectric Sensing) system, a wearable vest made by Sensible Medical Innovations. ReDS is based on technology that allows the military to “see through walls” and find survivors in collapsed buildings. In a medical setting, a device sees through the walls of the chest, sending an electromagnetic beam through the middle lobe of the right lung, measuring the lung fluid. Based on the readings, a physician might decide to raise or lower the dosage of diuretics, or hospitalize the patient if there is an extreme overload of fluid.

Dr. Pinney’s team is participating in a randomized multicenter clinical trial of the device, sponsored by Sensible Medical, that began in September 2015 and is to be completed in June 2018. The trial will compare the readmission rates of 380 patients hospitalized for heart failure. All participants are receiving the standard care, including follow-up phone calls and outpatient visits, but one group also goes home with a ReDS vest, with their readings transmitted to care providers. Since July 2017, Mount Sinai has also been using the device in its Rapid Follow-Up Clinic for recently discharged CHF patients. “We are one of only three centers to do this, so we are in the vanguard,” Dr. Pinney says. Among the 28 patients who have used the system since July, the 30-day readmission rate was about 9 percent, compared with 22 percent for heart failure patients overall.

The CardioMEMS™ device is an implanted sensor, about as wide as a dime, that checks for increased pressure in the pulmonary artery.

Mount Sinai is an early adopter of another device, CardioMEMS™, an implanted sensor made by Abbott that checks for increased pressure in the pulmonary artery—an early indicator of worsening heart failure. A small pressure sensor is implanted in the pulmonary artery using a catheterization procedure. Sensor readings are wirelessly transmitted to a secure website for clinicians. “If the pressures rise, we increase medication, and if they come down too low, we cut back,” Dr. Pinney says. “So it gives us a feedback loop to get smarter about prescribing medicine.”

Mount Sinai is also using apps to help monitor CHF patients. One is HealthPROMISE, a system for iPhone and Android, developed by the Mount Sinai AppLab. Patients are sent home with a blood pressure cuff and a scale that send data through the app to care providers. “We can track blood pressure, weight, and the answers to simple questions about the patients’ symptoms,” Dr. Pinney says.

A pilot study by Dr. Pinney’s team found that of 52 subjects using the app, four were readmitted within 30 days of discharge. “The CHF patients had a 7 percent readmission rate compared to the national readmission rate of more than 25 percent within 30 days of discharge,” according to an abstract of the study, presented in October 2017 at the Connected Health Conference in Boston.

Another app, being developed by Dr. Pinney’s group and a startup company, RecoverLINK, is also in clinical trials. It works similarly to HealthPROMISE but asks more detailed questions about patients’ symptoms, mood, compliance with medication, and general quality of life. In addition to remote monitoring, patients also receive personalized video messages from providers.

Dr. Pinney says that heart failure patients often underestimate the severity of their condition, saying “I just have a weak heart,” when the median survival after diagnosis is about five years—“as bad as many cancers, or worse.” He sees a significant opportunity to improve the lives of CHF patients. “There is a need to identify these individuals, refer them to a heart failure center of excellence like ours at Mount Sinai, and take advantage of the pharmacologic and device therapies that now exist.”

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Mount Sinai Featured in Special Report in The Wall Street Journal on the Future of Hospitals

Updated on Jun 30, 2022 | Featured, Research

Linda DeCherrie, MD

Mount Sinai Health System was featured in a recent special report in The Wall Street Journal titled “What The Hospitals Of The Future Look Like,” which spotlighted Mount Sinai’s Hospital at Home program.

“For some admissions, we can avoid the emergency department, but for most admissions like pneumonia, dehydration or a skin infection, we evaluate them in the ED and then send them home in an ambulance with an IV in place,” Linda DeCherrie, MD, clinical director of the mobile acute care team of Mount Sinai’s Hospital at Home Program, tells the Journal.

Read the article in The Wall Street Journal (requires paid subscription)

Mount Sinai’s Hospital at Home program has reduced the re-admission rate to the hospital, improved patient satisfaction outcomes, and cut the overall cost of delivering the care. Mount Sinai is working with Contessa Health.

The program is one of a number of initiatives Mount Sinai has launched focused on improving patient care.

“The goal is to care for each patient in the most appropriate setting, whether in a traditional hospital bed, an outpatient center or at home,” Kenneth L. Davis, MD, President and Chief Executive Officer of the Mount Sinai Health System, tells the Journal.

 You can learn more about Mount Sinai’s Hospital at Home Program  by watching this video

 

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A New Focus of Study for Liver Disease Specialists

Updated on Feb 27, 2018 | Featured, Research

A diseased liver with nonalcoholic steatohepatitis (NASH) showing liver cells containing large fat droplets, seen as empty spaces, with clusters of inflammatory cells

A normal liver with even-size liver cells

As the obesity epidemic continues to grow nationwide, so too has the incidence of related diseases such as nonalcoholic fatty liver disease (NAFLD). Estimates suggest that nearly one-third of all Americans have some form of fat in their liver, and as many as one-third of that population has the most worrisome form of NAFLD—nonalcoholic steatohepatitis (NASH), or liver inflammation and damage caused by fat buildup. Left unchecked, the disease may progress to a state of advanced scarring or cirrhosis, and also significantly increase the risk of developing primary liver cancer.

“There are approximately 20 to 35 million Americans who have NASH,” says Scott L. Friedman, MD, Dean for Therapeutic Discovery and the Irene and Dr. Arthur M. Fishberg Professor of Medicine and Liver Diseases at the Icahn School of Medicine at Mount Sinai. “The likelihood is that, within three years, NASH will supplant hepatitis C as the most common indication for liver transplantation.”

Long underappreciated and underdiagnosed, in part because there are often no specific symptoms that indicate liver disease, NASH is emerging as a primary focus of study. Dr. Friedman, who has been at the forefront of those efforts, is launching a new multidisciplinary working group that brings together the considerable resources of the Mount Sinai Health System and those of external stakeholders to advance the understanding, diagnosis, and treatment of NASH.

“This is an effort to link all the strengths of the Health System so we can establish standards for diagnosing and treating NASH,” Dr. Friedman says. “We also want to play a lead role in defining new therapies and offering them to our patients as quickly as possible, either through clinical trials or once they are approved, because there are currently no therapies approved for the treatment of NASH.”

In support of that effort, the Division of Liver Diseases has recruited Amon Asgharpour, MD, and Amreen Dinani, MD, Assistant Professors of Medicine (Liver Diseases), whose goal is to raise awareness about NASH and identify patients to participate in clinical trials.

“For example, I’m currently visiting the Mount Sinai Diabetes Center on Fridays to see patients and risk-stratify them because we know that patients with diabetes are more likely to have NAFLD,” Dr. Asgharpour says. “We have also started screening patients participating in the Weight and Metabolism Management Program at Mount Sinai St. Luke’s for liver disease, and we are providing them with strategies for weight loss. If we can help these patients lose weight, they can reduce the amount of fat and scarring in their liver and thus reduce their risk of developing potential complications from NASH.”

Many other collaborative initiatives are currently being discussed by the working group, ranging from researching the link between pathogenesis and fibrosis in liver adipose tissue, to engaging the Mount Sinai Liver Cancer Clinical Program to better understand the risk of liver cancer among NASH patients. “It’s going to be a very fertile and important time for generating ideas and establishing links across the different disciplines that are concerned about this disease,” Dr. Friedman says.

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Studying Diet and Multiple Sclerosis Symptoms

Updated on Feb 4, 2019 | Featured, Research, Your Health

Ilana B. Katz Sand, MD, with Amit Blushtein, a clinical trial participant, one of 18 multiple sclerosis patients randomized to follow a special dietary plan.

 

Neurologists have long suspected a link between diet and symptoms of multiple sclerosis (MS), but today, Ilana B. Katz Sand, MD, Assistant Professor of Neurology at the Icahn School of Medicine at Mount Sinai, and Associate Medical Director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis, is offering fresh insights.

Dr. Katz Sand and a team from the Icahn School of Medicine are currently conducting studies aimed at understanding the role of gut bacteria in inflammation and neurodegeneration. A recent publication of which Dr. Katz Sand is a co-author suggests that gut microbial composition in individuals with MS differs from that in healthy controls. Because gut bacteria communicate heavily with the resident immune system in the gut, as well as secrete molecules that can have distant effects, Dr. Katz Sand and colleagues hypothesize that changes in gut microbiota may contribute to the development of MS and other autoimmune diseases and also may influence disease course once MS is established. If further research confirms this, investigators like Dr. Katz Sand believe it may be possible someday to offer patients microbiome-based therapy to keep the bacteria in check.

One of the biggest drivers of gut microbial composition is diet, and it is this potential mechanistic link that led Dr. Katz Sand to begin studying dietary factors in MS. She says, “We want to better understand the inflammatory process, the neurodegenerative process, and the effect that diet has on MS symptoms. Our findings could be very important in understanding the onset of MS and how to treat it.”

Until recently, developing a methodology to study the possible connection between diet and MS has proved challenging because a double-blind randomized controlled trial doesn’t lend itself to studying diet. Dr. Katz Sand, who has pursued this clinical interest since she was a fellow, designed what she believes is a scientifically sound methodology that may help lay the groundwork for future clinical trials in this area.

She has developed a study to begin evaluating the hypothesis that a modified Mediterranean diet—which includes fresh fish, fruits, vegetables, nuts, whole grains, and avocados, and eliminates meat, dairy, and processed foods—may reduce inflammation characteristic of MS, whereby immune cells attack the myelin insulation that surrounds and insulates nerve fibers, causing problems with vision, balance, muscle control, cognition, and other debilitating symptoms.

She and her team have recruited 36 participants, 18 of whom have been randomized to follow this dietary plan for six months. All participants move through the study in small groups according to their assignment. The dietary-arm participants attend monthly meetings, led by Dr. Katz Sand, a nutritionist, and a research coordinator, that include presentations about various aspects of the diet to keep them motivated—one of the challenges of the study. There, they have the opportunity to discuss their experiences with their restrictive diet and to share tips.

Additionally, they are asked to complete questionnaires at the meetings and through regular emails. Certain markers, including salt, fatty acids, and carotenoids, are tested through lab work at the beginning and end of the study, and participants also are tested for the diet’s effects on body mass index, blood pressure, cholesterol, and glucose. The research team also employs quality-of-life scales that assess fatigue and measure depression, common MS symptoms. “We’ve got a nice group dynamic going,” says Dr. Katz Sand.

The non-dietary intervention participants attend study visits occasionally and also are offered seminars on topics of interest to MS patients. At the end of their study period, if they wish to start the diet, they are offered an opportunity to meet with the study’s nutritionist. The study, funded by the National Multiple Sclerosis Society, began in January 2017, and the last group of participants will finish in April 2018. The challenge for Dr. Katz Sand and her team will be to scale the study to include more participants, which they are planning to do in the near future.

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Integrative Medicine Pioneer Deepak Chopra, MD, Meets With Mount Sinai Research Team

Updated on Feb 21, 2018 | Featured, Research, Your Health

From left: Eric Schadt, PhD; Leena Nasser, Executive Director, Chopra Institute; Deepak Chopra, MD; Dennis S. Charney, MD; Ash Tewari, MBBS, MCh; and David L. Reich, MD.

Can meditation and other forms of alternative medicine be used in conjunction with traditional treatments to improve overall physiological and psychological health and well-being? This was a topic for brainstorming between best-selling author Deepak Chopra, MD, and basic science researchers and physician-scientists who attended a meeting hosted by Ash Tewari, MBBS, MCh, the Kyung Hyun Kim, MD Chair in Urology, Mount Sinai Health System.

The researchers, who were from the Department of Urology at the Icahn School of Medicine at Mount Sinai, joined Dr. Chopra, a pioneer in integrative medicine and co-founder of the Chopra Center for Wellbeing, to discuss their mutual interest in the study of the mind-body connection. Also attending were: Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System; David L. Reich, MD, President and Chief Operating Officer, The Mount Sinai Hospital; and Eric Schadt, PhD, Dean for Precision Medicine, and the Jean C. and James W. Crystal Professor of Genomics.

One topic they explored was to study, in a clinical setting, whether mind-body intervention through meditation and other practices such as yoga reduces inflammation and thus prostate cancer progression. In 2016, Dr. Schadt led a study with researchers from the University of California, San Francisco, and Harvard Medical School that assessed the biological impact of meditation. The study, which appeared in Translational Psychiatry and was partially funded by the Chopra Center for Wellbeing, found that meditation could ease stress and benefit the immune system.

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