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Researchers Develop Method to Identify Patient-Specific Drugs for Treating Diabetes

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This image shows human embryonic stem cell-derived pancreatic beta cell clusters after being transplanted into immunodeficient mice. 

Image credit: Drs. Hui Zeng and Min Guo

An innovative method that uses human embryonic stem cells to model type 2 diabetes caused by genetic mutations may enable researchers to identify drugs that could treat the disease. The research by Weill Cornell Medicine investigators was published Aug. 11 in Cell Stem Cell, and may extend the use of precision medicine to metabolic diseases.

Using precision medicine approaches that target genetic mutations "is becoming commonly used in cancer, and we think it may be an approach we can use for diabetes," said senior study author Dr. Shuibing Chen, an assistant professor of chemical biology in surgery at Weill Cornell Medicine.

Type 2 diabetes is a condition in which the body does not correctly respond to insulin, a hormone that regulates the amount of glucose, or sugar, in the blood. As a result, people with the condition have high blood sugar levels. While obesity is a risk factor for diabetes, people may develop the disease for a variety of reasons. Genomic studies scanning complete sets of DNA have revealed many genetic mutations implicated in diabetes. But the precise role of these mutated genes, including three chosen for this study — CDKAL1, KCNQ1 and KCNJ11I — has been largely unknown.

To determine the functional role of these genetic mutations, Dr. Chen and colleagues, including Dr. Todd Evans, the Peter I. Pressman, M.D. Professor in Surgery at Weill Cornell Medicine, and Dr. Johannes Graumann, an assistant professor of biochemistry at Weill Cornell Medicine-Qatar, used human embryonic stem cells that were directed to function like pancreatic cells. The cells, called beta-like cells, produce, store and release insulin.

The investigators found that mutations in CDKAL1, KCNQ1 and KCNJ11I hinder the function of beta cells, resulting in decreased insulin release and problems with the regulation of blood sugar levels. They found the same to be true when the cells were studied in a Petri dish or when used in mouse studies. CDKAL1 mutations also caused the beta cells to be highly sensitive to high blood sugar and high fat levels, both of which are a common cause of beta cell death in diabetic patients.

The investigators then screened 2,000 drugs and found "one compound in phase II clinical trials that corrects the CDKAL1-related beta cell defect," Dr. Chen said. Dr. Chen and study co-authors Dr. Hui Zeng and Dr. Min Guo have filed a patent on the application of this compound for the treatment of CDKAL-related beta cell defects. Based on these study results, scientists may be able to "develop gene variant-specific therapy for different categories of diabetic patients," she said.

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Stem Cell
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Enzyme Links Metabolic State to Inflammatory Response to Infection

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An enzyme that stimulates the breakdown of fats in immune cells helps trigger inflammation, or an immune response to pathogens, a new study by Weill Cornell Medicine researchers suggests. The findings enhance scientists' understanding of the connection between metabolism and inflammation, and may offer a new approach to treat dangerous infections such as pneumonia.

In their study, published July 25 in Nature Medicine, the team showed that the mitochondrial enzyme NOX4 regulates the activation of an inflammation-triggering protein complex called an inflammasome. It does this by increasing the levels of a key enzyme in fat breakdown, a process called free fatty acid oxidation.

"Inflammation is an important immune response to pathogens, but when it becomes chronic or if the response is too strong, it can hurt the patient," said senior author Dr. Augustine M.K. Choi, interim dean of Weill Cornell Medicine and Weill Chairman of the Weill Department of Medicine. "We knew that people with obesity-induced metabolic diseases, like diabetes, have an abnormal response to infectious agents, and in this paper we were able to make a connection between the two."

The connection is found in mitochondria, which in addition to being the cell's powerhouse plays an important role in the cellular stress response. The mitochondrial enzyme NADPH oxidase-4 (NOX4) produces reactive oxygen species (ROS), chemically reactive molecules that kill pathogens and signal that the cell is under stress, among other cellular responses. "Since NOX4 was linked to both diabetes and immunity, we wanted to understand what it was doing at the interface between the two," said lead author Dr. Jong-Seok Moon, a postdoctoral fellow in Dr. Choi's laboratory.

In mice infected with pneumonia, the researchers found a reduced inflammatory response and reduced mortality in mice lacking NOX4. Human immune cells lacking NOX4 also showed a reduced inflammasome response when presented with chemicals that normally provoke the cells. The group showed that these responses were lacking because there was a corresponding failure to increase levels of a key enzyme for mitochondria fatty acid oxidation, called CPT1a. Without this NOX-4-dependent boost in fat breakdown, the inflammatory response was blunted.

Currently, a drug that inhibits NOX4 is in phase 2 clinical trials to treat diabetic nephropathy, a condition where blood vessels in the kidney are destroyed. The team showed that the drug, GKT137831, was also effective in reducing inflammasome activation in mice, including in the pneumonia model. "Since this drug is already in phase 2 clinical trials, we think it is a good candidate for additional research as a treatment for patients with metabolic inflammation and infectious disease as well," said Dr. Choi, who is also physician-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center. "With the number of people affected by type 2 diabetes and obesity growing each year, we need to understand the link to inflammation and infection so we can treat these patients more effectively."

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Choi
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Experimental Therapy Could Treat Diabetes and Fatty Liver

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A new investigational therapy could be a major breakthrough in the treatment of both diabetes and fatty liver, according to Weill Cornell Medicine investigators.

Diabetes is a disease in which the pancreas either does not produce enough insulin or cells in the body fail to respond to insulin properly. Diabetic patients experience abnormally high blood sugar levels, which can lead to heart disease, stroke, kidney failure, and eye damage. The disease, which affects more than 29 million Americans, is treated with drugs that help to keep blood sugar within a normal range. Steatosis, or fatty liver, occurs in at least half of all diabetics, though the relationship between the two diseases is not clear. Steatosis can also occur in other patients, such as those with hepatitis. It is a condition in which fat accumulates in the liver, causing inflammation and damage to liver cells. Most patients with fatty liver can only be treated with lifestyle and diet changes.

In a study published in the February issue of Diabetes, Obesity and Metabolism, scientists at Weill Cornell Medicine have identified a new drug that appears to treat both of these diseases at the same time. The drug targets a specific protein, called retinoic acid receptor beta-2 (RARB2), which is critical in the development and functioning of pancreatic cells.

"This is a whole new class of drugs," said senior author Dr. Lorraine Gudas, chair of the Department of Pharmacology and the Revlon Pharmaceutical Professor of Pharmacology and Toxicology at Weill Cornell Medicine. "RARB2 is a new target for diabetes treatment. We are also excited because, currently, there is no medicine that effectively treats fatty liver, so this may be a breakthrough therapy."

The researchers studied mice with diabetes. The mice were given the new drug in their water. "We found that this drug restored normal blood sugar levels in the mice," said Dr. Xiao-Han Tang, an assistant research professor in pharmacology at Weill Cornell Medicine, who is an author on the paper. "And we also found that it reduced fatty liver symptoms."

The new drug, which has not been tested in humans, might have several advantages over current treatments. First, it is able to be taken orally, which makes it appealing for patients when compared to injectable diabetes medications. Second, it does not cause weight gain in mice. This is critical, said first author Dr. Steven Trasino, a postdoctoral fellow in pharmacology at Weill Cornell Medicine. "Some of the most commonly used anti-diabetes drugs cause weight gain, which can eventually make both diabetes and fatty liver worse. Avoiding that is a great advantage."

The ability to treat both of these diseases at once could result in major benefits to patients. "We think that this drug is a potential, potent anti-diabetic drug for humans," Dr. Tang said. "It's very exciting." Dr. Gudas and her team, which also includes Dr. Jose Jessurun, a professor of pathology and laboratory medicine and co-author of the paper, are making plans to bring this discovery to the clinic.

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Gudas Lab; Investigational drug AC261066 treats mice with diabetes
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Obesity Leads to "Silent" Vitamin A Deficiency in Major Organs

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Obesity impairs the body's ability to use vitamin A appropriately and leads to deficiencies of the vitamin in major organs, according to new research conducted at Weill Cornell Medicine.

Vitamin A is critical to the proper functioning of many systems in the body, including vision, fetal development, reproduction, immune responses, and wound healing. Vitamin A deficiency impairs these functions, and is also implicated in increased risk of respiratory infections, diabetes, infertility, and delayed growth and bone development. Because of these wide-ranging health effects, people are advised to get adequate amounts of the vitamin either through diet (eggs, milk, meat, and some fruits and vegetables are sources) or supplementation. But the study, published Nov. 2 in Scientific Reports, shows that obesity interferes with the body's ability to use vitamin A, even with adequate intake.

"Our research shows that, even if an obese animal consumes normal amounts of vitamin A, they have deficiencies of the vitamin A in major organs," said first author Dr. Steven Trasino, a postdoctoral fellow in pharmacology at Weill Cornell Medicine. "Obesity is categorized as a state of malnutrition, typically associated with consumption of too many calories and poor intake of essential nutrients. Our data expand on that definition by showing that obesity plays a role in the body's ability to use this essential nutrient properly."

Dr. Lorraine Gudas

The researchers fed mice a diet that had normal vitamin A levels, similar to the recommendations for human vitamin A intake.

"We found that normal-weight mice are healthy on that diet, but obese mice show severe vitamin A deficiencies in their livers, kidneys and pancreas," said senior author Dr. Lorraine Gudas, chair of the Department of Pharmacology and the Revlon Pharmaceutical Professor of Pharmacology and Toxicology at Weill Cornell Medicine.

When the obese mice lost weight, their vitamin A levels returned to normal. "Something about the state of obesity is impairing the body's ability to use vitamin A correctly," Dr. Gudas said.

What was particularly remarkable to the research team, which also included Dr. Xiao-Han Tang, an assistant research professor in pharmacology, and Dr. Jose Jessurun, a professor in pathology, was that the blood levels of vitamin A in all of the mice, including the obese mice, were normal. The deficiency was only noted when the researchers took tissue samples from various organs in the mice. "We call this ‘silent vitamin A deficiency' because it would not be picked up by a standard blood test for the vitamin," Dr. Trasino said.

The new findings suggest that obesity in humans is also associated with low vitamin A levels in many organs. Such deficiencies would have corresponding health effects.

"We know that obesity is associated with many illnesses, such as poor immune response and diabetes," Dr. Gudas said. "What we don't know is why. This gives us more information for understanding how the two go together, but many puzzles remain to be solved before we fully understand why obesity leads to less vitamin A in major organs of the body."

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Obesity and vitamin A levels
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Dr. Steven Gabbe Wins The Weill Cornell Alumni Association Award of Distinction

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Dr. Steven Gabbe '69, the senior vice president for health sciences at Ohio State University and emeritus CEO of OSU Wexner Medical Center, has been awarded the Weill Cornell Medical College Alumni Association Award of Distinction.

Established in 1949, the annual accolade recognizes a Weill Cornell alum who has demonstrated outstanding achievement in research, education or patient care, and has brought acclaim to the medical college. Dr. Gabbe received the award at the Alumni Award of Distinction dinner on May 27.

"It was an incredibly meaningful surprise winning this award, especially when I think of all the Weill Cornell alums that I've known and worked with over the years who are so accomplished and have done so much," said Dr. Gabbe, who is also a professor of obstetrics and gynecology at Ohio State University.

Dr. Gabbe is one of the world's leading experts on the complications of diabetes and pregnancy. He has helped define the glucose treatment protocols for pregnant women with type 1 diabetes. He was also involved in an international study funded by the National Institutes of Health that led to new diagnostic criteria for gestational diabetes. The study was devoted to defining the criteria for fetal risk associated with maternal glucose levels and pregnancy.

Dr. Gabbe served on the faculty of six universities: the University of Southern California, University of Colorado, University of Pennsylvania and the University of Washington. He spent nine years as the chair of Ohio State University's Department of Obstetrics and Gynecology. He was also dean of the Vanderbilt University School of Medicine for seven years, and is currently a member of the Institute of Medicine and senior editor of Obstetrics: Normal and Problem Pregnancies, a leading obstetrics textbook.

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Dr. Steven Gabbe, center, accepts the Weill Cornell Medical College Alumni Association Award of Distinction from Dr. Laurie H. Glimcher and Dr. Spencer Kubo at an awards dinner on May 27. Photo Credit: Studio Brooke
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Diabetes Prevention in Qatar Should Focus on Lifestyle Factors

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Demographic and lifestyle factors are largely responsible for an alarming increase of diabetes in Qatar and other countries in the Middle East and North Africa, according to a new study from Weill Cornell Medical College and Weill Cornell Medical College in Qatar.

The study, published in the December issue of Qatar Medical Journal, found that a more “westernized” lifestyle, characterized by calorie-rich diets and reduced physical activity, has made people in the region more susceptible to developing type 2 diabetes mellitus and other associated chronic conditions. Investigators say the findings underscore a need to raise awareness of diabetes, promote physical activity and emphasize the risks associated with obesity.

"The Qatar National Health Strategy has identified diabetes as one of the high-priority diseases for preventive healthcare, and for good reason," said senior author Dr. Alvin I. Mushlin, the Nanette Laitman Distinguished Professor of Public Health and a professor of healthcare policy and research and of medicine at Weill Cornell Medical College. "In addition to its direct effect on health and quality of life, diabetes is a cause of conditions such as diabetic retinopathy, kidney failure, cardiovascular disease and associated heart attacks, strokes and earlier death."

Paradoxically, the increase of diabetes and other non-communicable diseases in this region is largely tied to major improvements in economic conditions, the investigators said. There have been remarkable improvements in the health infrastructure, a lengthening of life expectancy, an increasingly aging population, and a fast pace of urbanization.

To determine the risk factors that have led increased incidence of the disease, the investigators looked at patient records for more than 450 patients — including Qatari nationals and immigrants — with type 2 diabetes who had received care from Hamad Medical Corporation Hospital's outpatient adult diabetes clinics from 2006-2008. They compared these patients to nearly 350 other patients who received care from various outpatient and inpatient clinics at the hospital.

Since more than 80 percent of the population of Qatar consists of immigrants from countries throughout the Arab world, South Asia and other regions, the researchers also conducted a sub-analysis of only Qatari nationals to see if this group had a different risk factor profile than the population at large.

"In our study, Qatari nationality was the strongest risk factor for DM, followed by higher income, obesity, no college education and no vigorous or moderate exercise," said lead author Dr. Paul J. Christos, a lecturer in healthcare policy and research in the Division of Biostatistics and Epidemiology.

"While further evaluation of DM risk factors among the Qatari population (as opposed to the resident population) is important and of interest," said study co-author Dr. Laith Abu-Raddad, an associate professor and principal investigator of the Infectious Disease Epidemiology Group at Weill Cornell Medical College in Qatar, "these findings highlight the need to focus short-term DM interventions on addressing demographic/lifestyle risk factors to achieve substantial and timely declines in DM levels."

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Dr. Alvin I. Mushlin
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Vitamin A Deficiency May Be Involved in Type 2 Diabetes, Researchers Say

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Investigators have long sought the answer to a vexing question: What are the biological mechanisms involved in the development of type 2 diabetes? A recent study from Weill Cornell Medical College researchers suggests that the culprit may be a lack of vitamin A, which helps give rise to the cells, called beta cells, in the pancreas that produce the blood sugar-regulating hormone insulin.

The researchers found in mice models that a lack of vitamin A spurred the death of beta cells, stunting the production of insulin, which is tasked with metabolizing sugars that come from food. These findings, published Dec. 1 in The Journal of Biological Chemistry, may offer new clues into the cause of type 2 diabetes, which is characterized by insulin-resistance, and in advanced cases, inadequate numbers of insulin-producing beta cells.

When the investigators removed vitamin A from the rodents’ diet, they found that the mice began to experience massive losses of beta cells, which resulted in drops in insulin and a big increase in blood glucose. The researchers then reintroduced vitamin A into the animals’ diet and found that the number of beta cells stabilized, insulin production was higher and that blood glucose returned to normal levels.

Because patients with type 1 diabetes and those with advanced type 2 diabetes experience a loss of beta cells, there is a strong interest in developing new treatments that either preserve or replenish them. “From a therapeutic point of view, our research is a very important contribution because there are no drugs available to do this,” said first author Dr. Steven Trasino, a postdoctoral associate in the Department of Pharmacology.

Scientists have understood that vitamin A is essential for the production of insulin-producing cells during fetal development, but whether that role continued into adulthood was not known. The researchers sought to answer that question by using both normal mice and mice that had a genetically impaired ability to store vitamin A.

"While there are thousands of publications on diabetes, there hasn’t been much research on the effects of removing vitamin A from the diets of animals, acting as a model for human disease," said senior author Dr. Lorraine Gudas, chairman of the Department of Pharmacology and the Revlon Pharmaceutical Professor of Pharmacology and Toxicology at Weill Cornell. "How the removal of vitamin A causes the death of the beta cells that make insulin in the pancreas is an important question we want to answer. These beta cells in the pancreas are exquisitely sensitive to the dietary removal of vitamin A. No one has found that before."

These early-stage findings raise the question of whether vitamin A deficiency is involved in humans and animals with type 2 diabetes, either through inadequate diet or through a metabolic defect. They also spark questions about whether a synthetic analog of vitamin A could reverse the disease’s effects.

"Our study sets the platform to take these studies further into pre-clinical and clinical settings," Dr. Trasino said.

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hyperglycemia in Vitamin A-deficient mice
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Aggressively Controlling Blood Sugar Lengthens Life in Patients with Type 1 Diabetes

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Patients with type 1 diabetes who closely monitor and control their blood sugar live longer than those who don't, according to new research funded by the National Institutes of Health.

The study, published Jan. 6 in the Journal of the American Medical Association, is the result of a nearly 30-year, two-part, multi-site trial following nearly 1,500 patients with type 1 diabetes. The findings provide physicians and their patients with hard evidence showing that intensively maintaining near-normal blood sugar levels translates into improved overall health outcomes.

"I think anyone who has to have a treatment would want to weigh the risk and benefits," said Dr. David Brillon, a professor of clinical medicine at Weill Cornell Medical College and an author on the study who has led the trial at the medical college since the late 1980s. "It's important to study these long-term outcomes and be able to tell patients, 'Yes, you can use intensive glucose-lowering treatments and try to attain glucose levels that will reduce your risk of mortality.'"

While aggressively controlling blood sugar is the accepted treatment for type 1 diabetics today, it was unclear in the 1980s whether that therapy would be effective in reducing diabetes complications, Dr. Brillon said. Investigators at the time were unsure whether diabetes complications occurred as a result of high blood sugar, or if they were associated with other underlying — perhaps genetic — conditions.

Investigators at Weill Cornell and at 28 other sites in the United States and Canada enrolled 1,441 people between the ages of 13 and 39 with type 1 diabetes for the randomized Diabetes Control and Complications Trial, which began with a feasibility phase in 1983. Half of the patients checked their blood glucose levels daily and administered insulin once or twice a day, while the other half monitored glucose levels four or more times a day, particularly before and after meals and at night. Those in the intensive monitoring group also utilized more advanced insulin delivery protocols administering insulin three or more times a day. In some cases, intensive treatment included pumps, which provide a steady and measured dose of insulin that closely mimics the body’s normal release of the hormone.

The trial prematurely ended in 1993, as researchers found that the patients in the intensive glucose monitoring group had substantially less eye, nerve and kidney disease than their peers in the other group. All patients were advised to follow the intensive blood glucose monitoring, and nearly all enrolled in the Epidemiology of Diabetes Interventions and Complications follow-up study that allowed physicians to monitor their long-term health outcomes.

Investigators found that participants in the intensive monitoring group had a 33 percent lower risk of dying compared to those in the conventional group. While 22 percent of patients died from cardiovascular diseases and 18 percent from acute diabetes complications characterized by dangerously high or low blood glucose, not all deaths were attributable to diabetes.

"If someone with type 1 diabetes is able to attain glucose levels that are closer to the normal range, I think that imparts positive effects for the patient in general," Dr. Brillon said. "In addition to less eye, kidney, nerve and heart disease, these patients come away with a reduction in overall mortality."

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Dr. David Brillon
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Closing the Gap

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Through community outreach, students and faculty tackle health disparities among poor and minority New Yorkers

By Heather Salerno

Earlier this year, Ana Reyes promised herself that she'd start living healthier. She knew she needed to make some changes; at fifty-one, the mother of three carried 270 pounds on her five-foot-one frame. So she began eating more vegetables, drinking lots of water, and taking long power walks —and in five months, she’d shed twenty pounds. But Reyes, who lives in a public housing development in East Harlem, knows she should do more. She doesn’t have a primary care provider, and her high blood pressure hasn’t been monitored regularly since she was pregnant with her youngest child, now ten. As for cholesterol, body mass index, or blood sugar? Reyes can’t remember the last time they were checked.

That's why she's at the Johnson Houses Community Center on this Saturday afternoon in May, taking advantage of a free health screening conducted by Weill Cornell’s Heart-to-Heart program, a student organization sponsored by the Clinical and Translational Science Center (CTSC). The event has a party vibe, thanks to a flurry of red and white balloons and a DJ spinning dance tunes. But the mission is serious: staffed by physicians, nurses, and students, Heart-to-Heart aims to curb cardiovascular disease in New York City’s underserved, minority, and ethnic communities. Faculty and clinicians-in-training — including medical and physician assistant students from Weill Cornell and nursing students from Hunter College — work to identify people who may already have a chronic disease, as well as to offer preventive advice to those on the cusp of dangerous conditions.

On a stage next to the center's basketball court, Reyes moves from station to station as smiling Heart-to-Heart volunteers measure her waist circumference, check her pulse, and prick her finger to draw blood, which is analyzed in less than seven minutes. She doesn't react much when given the straight numbers: total cholesterol of 258 (above normal); glucose level of 111; a BMI of 46.54 percent (considered morbidly obese). But she's visibly concerned after sitting down with Sebhat Erqou, MD, PhD, an instructor in medicine at Weill Cornell, who gently explains that the results put her at a much higher risk for type 2 diabetes, heart attack, or stroke. "The good thing is that you're doing all the right things, because exercise and weight loss can reverse it in most people," Erqou tells her. "Your doctor in the future may want to put you on diabetes medication, but you could prevent that by doing the things we're talking about. It's not alarming, but it's something to watch."

Referred to an agency that can assist her in finding a regular doctor who takes her government-sponsored insurance plan, Reyes vows to seek follow-up care. "This is the first time I ever heard I was pre-diabetic," she says with a frown. "It just tells me I have to work harder."

Unfortunately, Reyes's diagnosis isn't the exception in her neighborhood — it's the rule. In East and Central Harlem, six in ten adults and about one in four children are overweight or obese. As a result, these largely African American and Latino communities have a disproportionately higher prevalence of obesity-related illnesses such as diabetes, heart disease, and other major ailments. Of the more than 3,000 people that Heart-to-Heart has screened at more than fifty events throughout New York City since 2010 — about half of whom have a household income of $20,000 a year or less — nearly 60 percent are pre-diabetic or diabetic. "We need to make these individuals aware of their conditions early on and convince them to make small lifestyle changes that can make a big difference in the long term — not just in keeping them healthy, but in also reducing the healthcare costs for the nation," says Jeff Zhu, the CTSC’s manager for community research, relations, and outreach. Says Julianne Imperato-McGinley, MD, the CTSC’s program director and associate dean for translational research: "Cardiovascular disease is one of the easiest diseases to prevent. If you can discover it, diagnose it, and intervene early, you don't need to go through, say, triple-bypass surgery down the road."

Heart-to-Heart is one of several CTSC outreach programs striving to address the health inequities that plague socioeconomically disadvantaged New Yorkers. Since 2009, the Center has provided Community Interactive Video Conferencing (CIVIC), which connects experts from Weill Cornell and partner institutions with underserved communities throughout New York City and Long Island. Connecting with audiences at faith-based institutions and community centers, it addresses preventive health and other topics in an interactive, town-hall-style format; its latest initiative provides "hands-only" CPR training in conjunction with the Ronald O. Perelman Heart Institute. "Community engagement is an important function of the CTSC," Imperato-McGinley notes. "With CIVIC and Heart-to-Heart, we've made a firm commitment to being a partner in addressing disparities in New York City." In 2012, the CTSC produced a successful staged reading of Miss Evers' Boys, a Pulitzer-nominated play about the notorious Tuskegee syphilis study written by Cornell theatre professor David Feldshuh, MD. The event featured a panel — moderated by Joseph Fins, MD '86, the E. William Davis Jr., MD, Professor of Medical Ethics and chief of the division — that addressed the issues the play raises.

For Weill Cornell, combating health disparities is an ongoing commitment that goes back decades. For example, the Medical College founded its Travelers Summer Research Fellowship program — designed to help pre-med students from under-represented minority groups dive deeper into issues that affect the underserved — nearly a half-century ago. In 2009, an $8 million grant from the NIH established the Comprehensive Center of Excellence in Disparities Research and Community Engagement, (CEDREC), charged with developing community-based initiatives to improve the health of this hard-to-reach population by providing general health education.

young doctors; Closing the Gap

Through a variety of programs, Weill Cornell is reaching out to socioeconomically disadvantaged New Yorkers.

Normally, says CEDREC's director, Carla Boutin-Foster, MD, MS '99, research is conducted in academic settings, which many in these communities find off-putting. So the goal of these programs is to connect one-on-one with patients in places where they feel most comfortable, even if the locations are unconventional. "There are social factors that pose challenges for some people to access proper care in traditional healthcare settings," says Boutin-Foster. "We want to make sure that we reach people where they are and not rely on traditional healthcare or research settings."

Boutin-Foster adds that those social factors also contribute to the poor health seen frequently among the groups that the Center serves. Minorities are more likely to live in areas where fresh produce and other healthy foods are scarce, with few opportunities for safe, affordable physical activity. Language barriers and transportation issues block some from visiting a physician.

Among many African Americans, there is still a lingering mistrust of medical research that dates back to the Tuskegee study; Boutin-Foster points to research showing that some minorities may feel that doctors treat them differently because of their race or ethnicity. In addition, routine checkups and treatment for chronic diseases often prove too costly for the uninsured. "When someone has to take care of a family and worry about paying the bills, health may not be a priority," says Boutin-Foster. “It’s not a deficiency that they have; it’s just reality. People are constantly making tradeoffs when it comes to their own health, especially when they don’t feel ill. Hypertension tends to be silent until someone has organ damage; so, for the most part, do renal disease, stroke, and heart failure from hypertension. So 'why take a day off from work when that's going to cost part of my salary or even my job?' It's complicated."

For Boutin-Foster, any effective health intervention or research study requires a grassroots effort, one that embeds itself in the population being served. Therefore, faculty working on CEDREC projects collaborate with partners — including barbershop owners, faith-based organizations, and local physicians — who are trusted by the residents of those communities. To recruit participants for the Small Changes and Lasting Effects (SCALE) project — a five-year, multi-phase trial to help overweight or obese African Americans and Latinos lose weight by adopting tiny shifts in their dietary and exercise habits — researchers sought assistance from prominent church leaders, well-established health centers, and PTA associations in Harlem and the South Bronx. Pastoral support, in particular, was instrumental in motivating church members to take part in SCALE, according to Erica Phillips-Caesar, MD, an associate professor of clinical medicine and co-director of CEDREC's Community Engagement Core. In fact, on the day that Phillips-Caesar and her colleagues introduced the program at Harlem's Abyssinian Baptist Church, the influential Rev. Dr. Calvin Butts based his sermon on the issue. "Especially in communities of color, the church has served as a leader in a number of different realms — whether it be health, politics, or social issues," says Phillips-Caesar. "That's very powerful in terms of creating a community of people who are going to support this."

The SCALE team is currently finishing data collection from the approximately 300 adults who enrolled in the program. Participants started by making a relatively minor change in their diet, such as eating from a smaller plate or not skipping breakfast, along with setting a reasonable goal for daily physical activity. Then a community health worker followed each patient for one year, meeting with them regularly and working together on strategies to best achieve those objectives. The intent was to have participants lose at least 7 percent of their total body weight — but the program had wider goals. The community health workers were also trained to navigate unique, unrelated challenges. When one woman had difficulty committing to the program because she has an autistic child, her worker helped find support services. "The intervention is not one-size-fits-all," says Phillips-Caesar. "Our community health workers do a lot of counseling and outreach on aspects of people's lives that have nothing to do with weight."

Just as the SCALE project relied heavily on churches to spread the word, the HeartSmarts program at the Perelman Institute highlights the important role that religion can play in disease-prevention efforts in underserved communities. Created by Naa-Solo Tettey, EdD, the Institute’s cardiovascular health education and community outreach coordinator, HeartSmarts uses the Bible to teach minority churchgoers about the benefits of a healthier lifestyle. "I saw a lot of programs that were faith-based, meaning that they were in the churches but they weren't actually utilizing the church culture or the Bible," says Tettey. "They were just programs people had created and given to the churches. So I thought it would be interesting to combine the science with actual scripture."

For example, during a lesson about understanding one's risk of heart disease, Tettey quotes from I Corinthians: "Do you not know that your bodies are temples of the Holy Spirit, who is in you, whom you have received from God? You are not your own. . . . Therefore honor God with your bodies." She incorporates other key passages when talking about the importance of physical activity, portion control, and optimal heart rates and cholesterol levels.

Since 2012, Tettey has trained about eighty "ambassadors" from the Flatbush Seventh-Day Adventist Church in Brooklyn, the Presbyterian Church of St. Albans in Queens, and dozens of other ministries throughout New York City and Long Island. Those representatives then educate fellow congregants who sign up for a ten-week HeartSmarts course. In the first year alone, more than half the participants reduced their blood pressure and waist circumference. The message, however, has spread beyond those who attend class. "Now, after church services, they're not serving fried chicken anymore. They're serving baked chicken and vegetables," says Tettey. "So even if every person in the church doesn't take the class, they're impacted in some way by having that ambassador there."

At CEDREC, Boutin-Foster hopes to secure funding for projects that focus on health disparities among immigrants, especially low-wage workers in the service industry. The Center is currently fostering partnerships with groups that support day laborers and taxi drivers; it's also teaming up with the New York City office of Cornell's Worker Institute and the National Domestic Workers Alliance to craft interventions for some of the approximately 200,000 domestic workers in New York City including nannies, housecleaners, and elder-care providers. K. C. Wagner, co-chair of the Equity at Work Initiative, notes that even though domestic workers are responsible for the well-being of those in the households where they're employed, they're often unable to attend to their own health concerns. "That is the irony," she says. "Because of their role as workers in an informal economy — some of whom are documented, some of whom are not — they don't have access to healthcare resources."

Moving forward, Boutin-Foster hopes that CEDREC will become a training ground for students interested in studying healthcare disparities. She agrees that larger social policies are needed to address the root causes of such disparities, but she insists they're not enough. A policy can't motivate someone to adopt a healthier lifestyle; that's why she says physicians-in-training must take part in hands-on projects that provide patients with tools that will enable them to become more active in their care. Boutin-Foster believes that medical centers like Weill Cornell must teach physicians to be part of the solution, showing them that well-designed educational and outreach efforts can translate into positive, real-world changes. "It's not just something in a book," she says. "I live in Brooklyn, and I see these disparities on a daily basis; all I need to do is walk down the block or ride the subway. So for me, it's personal."

This story first appeared in Weill Cornell Medicine, Vol. 13, No. 3.

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Sanford I. Weill Retires as Chair of the Weill Cornell Board of Overseers After 20 Years of Transformative Leadership

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Jessica M. Bibliowicz, Successful Business Executive, Named New Chair of the Board

NEW YORK (December 9, 2014) — After 20 years of bold and visionary leadership that has transformed Weill Cornell Medical College into a global healthcare enterprise, Sanford I. Weill will retire as chair of the Weill Cornell Board of Overseers on Jan. 1. Jessica M. Bibliowicz, a successful entrepreneur in the financial services business for nearly three decades, who has served on the Board of Overseers for the past decade, will succeed Mr. Weill, the new chair emeritus.

Jessica M. Bibliowicz and Sanford I. Weill

Jessica M. Bibliowicz and Sanford I. Weill. All photos: John Abbott

The transition comes as the 116-year-old medical college embarks on a new chapter that builds upon the landmark successes Mr. Weill has realized in his two decades as chair. His enduring dedication to the institution that bears his name has resulted in an unprecedented expansion that is exemplified in Weill Cornell's excellence in medical education, biomedical research and clinical care. In collaboration with medical college leadership, Ms. Bibliowicz will help lead Weill Cornell as it continues to break new ground in New York and abroad by expanding its clinical enterprise and forging public-private partnerships that accelerate groundbreaking scientific discoveries for patients. Working closely with Dr. Laurie H. Glimcher, the Stephen and Suzanne Weiss Dean of Weill Cornell Medical College, Ms. Bibliowicz will help guide its transformation of medical education and drive dialogue on innovative healthcare delivery models that optimize the value and quality of patient care.

"When I joined the Board of Overseers more than 30 years ago, I was driven to try and make a difference in the world," Mr. Weill said. "It's truly humbling to see just how much of an impact Weill Cornell has had around the globe, and I believe we are poised to thrive far into the future. Weill Cornell Medical College is more to me than just an esteemed medical school — the people here are my extended family. I could think of no one better than Jessica to shepherd Weill Cornell into the next stage of its evolution."

"It's an honor and privilege to be able to support Weill Cornell Medical College's tremendous efforts to educate, innovate and heal," Ms. Bibliowicz said. "As a Cornell University alum, it's especially meaningful to me to try and help take this distinguished institution to the next level of excellence in New York and beyond. Our ever-changing healthcare landscape has sparked exciting opportunities to help shape national conversation, and I'm eager to work with Dr. Glimcher and the Board of Overseers as we strive to improve and prolong human health."

Dr. Laurie H. Glimcher, Sanford I. Weill and Jessica M. Bibliowicz

In the three decades he has served on the Board of Overseers and in the two decades he has been chair, Mr. Weill has been much more than a governing force. His benevolence and unwavering resolve to ensure a healthier future has touched every program area at Weill Cornell, establishing the medical school as an innovator in basic, clinical and translational research, and forging a new paradigm for global engagement and medical education.

Under Mr. Weill's leadership, the medical college has built bridges nationally and abroad. Weill Cornell forged an affiliation with Houston Methodist in Texas and, with Cornell University, established a medical school in Doha, Qatar. Since its inception in 2002, Weill Cornell Medical College in Qatar, which offers a Cornell University medical degree, has created 181 new doctors who have continued their graduate medical training in residencies and clinical research at outstanding institutions in the United States and Qatar. The Weill Cornell Qatar location has also established a world-class biomedical team and contributed to Qatar's goal of becoming a knowledge-based economy. In addition, Weill Cornell in 2007 established a formal affiliation with Bugando Medical Centre and the Weill Bugando University College of Health Sciences in Mwanza, Tanzania, named in recognition of the Weills' support. Weill Bugando has graduated an average of 100 new doctors every year for the past seven years in Mwanza, expanding Tanzania's core of providers who are empowered to deliver the best patient care, despite a resource-limited setting. This unique educational partnership has spurred new possibilities for cultural exchange, providing medical students at Weill Cornell in New York and residents at NewYork-Presbyterian Hospital with the opportunity to spend a month or two in Mwanza practicing medicine the way it used to be, with limited modern technology. They return to New York with a greater sense of gratification that reaffirms their commitment to global health and a career in academic medicine.

In recognition that building a healthier future also requires training an exceptional cadre of new doctors and scientists, Mr. Weill and his wife Joan in 1992 established the Joan and Sanford I. Weill Education Center, the heart of the medical college's education program, with their first gifts to Weill Cornell. The Weill Education Center comprises the Weill Auditorium and 20 classrooms and teaching laboratories outfitted with modern audio-visual, networking and wireless technology to provide the next generation of medical professionals with the best environment for learning.

Sanford I. Weill

In 2007, Weill Cornell opened the Weill Greenberg Center in New York City, the medical college's flagship and award-winning ambulatory care center, and in January opened the adjacent Belfer Research Building, a transformative 18-story, state-of-the-art facility that ensures that the medical college remains at the forefront of scientific discovery. Their proximity to each other ensures that breakthroughs made in the laboratory can be rapidly applied to patient care as improved treatments and therapies. Weill Cornell has successfully recruited some of the world's leading physicians and scientists to conduct this translational research. Last year, the Weills established the Weill Center for Metabolic Health, which strives to understand the basic biology and genetics of diabetes, obesity and metabolic syndrome, and translate discoveries into next-generation therapeutic approaches. Weill Cornell is conducting a national search for a renowned scientist to lead these efforts.

A self-made man who exemplifies the philosophy of leading by example, Mr. Weill, Mrs. Weill and the Weill Family Foundation have generously given more than $550 million in gifts to support Weill Cornell Medical College. They include a groundbreaking $100 million gift in 1998 — at the time the largest in Cornell University's history — a second $100 million gift in 2002, a $250 million gift in 2007 and another $100 million gift in 2013 to establish the Weill Center for Metabolic Health, as well as the Joan and Sanford I. Weill and the Weill Family Foundation Global Health Research Laboratories. In honor and appreciation of their unparalleled dedication and enduring commitment, the institution in 1998 was renamed Weill Cornell Medical College. With an additional gift of $50 million to Cornell University, the Weills' total giving tops $600 million.

The Weills' altruism inspired and galvanized Weill Cornell's numerous, loyal donors to support the medical college. In Mr. Weill's 20 years as chair, the medical college has raised $3 billion. Earlier this year, Weill Cornell celebrated the Weills' legacy by naming its department of medicine the Joan and Sanford I. Weill Department of Medicine.

"What Sandy has done for Weill Cornell, New York and the world is just breathtaking — it's a labor of love that will touch the lives of generations," Dr. Glimcher said. "His unwavering leadership, profound magnanimity and steadfast resolve to enhance medical education, advance discoveries and enrich clinical care is his lasting legacy. Jessica is an outstanding choice to assume Sandy's mantle and steer Weill Cornell into the future. I couldn't be more thrilled for what's to come."

"Sandy is a businessman, entrepreneur, philanthropist, visionary leader, chairman emeritus of Citigroup, Cornell alumnus and my good friend," said Cornell University President David Skorton. "As chair of the Board of Overseers of Weill Cornell Medical College, he has nurtured the college's growth, guided its progress and expanded its capacity for rigorous medical education, path-breaking research and superb clinical care — to the enormous benefit of our students, faculty, researchers and patients. I am delighted that Jessica Bibliowicz, who has provided exemplary leadership to the university and the medical college, has agreed to take on this new role as chair of the Board of Overseers."

"It is impossible to overstate the impact that Sandy has had on Weill Cornell Medical College, and on the whole of Cornell University, during his time as chair of the Board of Overseers," said Robert Harrison, chair of the Cornell University Board of Trustees. "He is someone who can not only articulate a strong and inspirational vision, but also bring people together to do what it takes to make the vision a reality. Although I will miss working with Sandy, I am very much looking forward to working with Jessica in her new role. She has been a very effective trustee and overseer for many years and clearly has the talent and energy to lead the Board of Overseers and the medical school to new heights."

About Jessica M. Bibliowicz

A Cornell University graduate in 1981 and after working 18 years in financial services, Ms. Bibliowicz became CEO of National Financial Partners in 1999, a financial services firm that specializes in benefits and wealth management. The company went public in 2003 and was sold to Madison Dearborn in 2013. Ms. Bibliowicz joined the Weill Cornell Board of Overseers in 2004. She is also a member of the Cornell University Board of Trustees and a member of the Cornell NYC Tech Campus Task Force. Currently, Ms. Bibliowicz is a senior advisor at Bridge Growth Partners and serves on the board of directors of Sotheby's(NYSE: BID); Realogy (NYSE: RLGY); and the Asia Pacific Fund (NYSE: APB). She is a board director/trustee of Prudential Insurance Funds and is also on the board of Jazz at Lincoln Center.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, Cornell University is the first in the U.S. to offer a M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with Houston Methodist. For more information, visit weill.cornell.edu.

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