A promising new approach to stem cell research brings together research groups at the University of Chicago with other collaborators to apply their complementary expertise in stem cell and developmental biology, genetics and genomics and beta-cell physiology to address the problem of generating mature human beta-cells that can be used therapeutically in patients with type 1 diabetes (TID). In particular, Dr. Philipson and Bell have been working with James Wells, PhD of the University of Cincinnati and his lab to continue the momentum of this research.
As Kovler scientists continue their research in this area- with generous support from Friends United- they are thinking through the idea that cells made from adults can be taught to make insulin and might be used to treat diabetes. The technical term for these cells is induced pluripotent stem cells (iPSCs), and Dr. Philipson thinks they can help teach all of us how insulin-secreting cells (beta cells) are properly made. These adult stem cells are made from skin biopsies of adults, not embryos, and using genetic methods can be turned into stem cells that can do almost anything.
According to Dr. Philipson, the next phase of this collaborative project is to “send blood samples to Dr. Wells and his team to start the process of making adult-stem cells from white blood cells. Our specific research initiative is to take advantage of our expertise in unusual, genetic forms of diabetes called monogenic diabetes.” Using iPSCs derived from patients with monogenic forms of diabetes due to a mutation in key genes affecting beta-cell development or maturation of the insulin secreting cells, Drs. Philipson, Bell and others hope to learn how to create improved beta cells.
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I am the Program Coordinator for the Diabetes Prevention Program Outcomes Study, a multi-center study which has been ongoing since February 1996. We ended recruitment in February, 1999. There are two staff members working on the DPPOS here – myself and Rina DeSandre. We have worked together since the study’s inception!
Our study is looking at how to prevent diabetes in people at high risk. It was a very stringent screening process, but finally after three years we finished recruitment and randomized 153 people. There are three treatment groups now. One is using the medication metformin, which is currently indicated for treatment of diabetes, one group is the placebo and the other group is intensive lifestyle. Those in the intensive lifestyle group have a goal to lose 7% of their weight and do at least 150 minutes of moderate exercise (like a brisk walk) each week.
Since our study has been going on so long, we actually have some results initially published in the New England Journal of Medicine in 2001. It was found that lifestyle was almost twice as effective (a 58% reduction in risk) at preventing diabetes as taking metformin for prevention. However, the metformin did have a 31% reduction in risk of getting diabetes.
Our participants are quite loyal – with a greater than 90% retention rate. They see us twice a year now. We also have classes on a quarterly basis and all are invited and can bring a guest as well. There are various topics ranging from stress reduction to resistance training to eating a Mediterranean based diet.
We are planning on continuing the study until 2014. However, we are also in the process of planning for another extension. We still have many questions to be answered and our participants are also eager to continue. (What a great job I have!)
Program Coordinator, DPPOS
Over in the Transplant Center at The University of Chicago we are researching the transplantation of islet cells from a deceased donor’s pancreas into a liver of the patient. Islet cells are the cells from the pancreas that produce insulin. First the Islet cells are isolated in a special solution, and then inserted into a liver vein much like any other solution. This is a non-invasive procedure.
Research on islet transplantation could be helpful for those with Type I to have better control of blood sugars. This research is currently being conducted in those with Type I who have trouble with low blood sugars, where they are no longer able to tell their sugar is too low during those light headed, shaky, wonky (yes, I think I made that word up) moments.
This research is being done in the transplant center because the islet cells that are used come from donated organs, just like a whole pancreas transplant. This research is similar to other studies that have been completed around the country and the world but applies the newest technology for better results.
To find out more about the islet cell transplant research check out the following websites: www.uchospitals.edu/specialties/transplant/pancreas-islet.html
The last several decades have witnessed a dramatic deterioration in our health with the burgeoning obesity and diabetes epidemic. While lifestyle factors such as a poor diet and physical inactivity certainly contribute, these factors fail to explain the magnitude and rapidity of the diabetes explosion. As such, the search is on for contributing factors, and my laboratory has focused on the potential contribution of environmental pollutants to the surge in metabolic diseases.
Building off of my life-long interest in the environment, our work focuses on how chemicals with the capacity to alter hormonal signaling, environmental endocrine disruptors or EDCs, alter energy balance. We have multiple ongoing projects looking at the effects of EDCs on fat cell development and function, EDC-mediated disruption of insulin signaling (a precursor to the development of diabetes), and the effects of EDCs on energy metabolism in mice exposed to these chemicals in their food, similar to the way humans are exposed.
It is my sincere hope that these efforts will not only help us better understand the factors that contribute to the development of diabetes, but that this work will also provide the foundation for better regulatory action to eliminate diabetes-promoting chemicals from our environment.In addition to this work, we are currently developing research projects to explore the potential impact of various EDCs on the development of obesity and diabetes in humans naturally exposed to these chemicals. In addition to examining the effects of environmental pollutants on the development of type 2 diabetes, our collaborative projects will specifically look at both type 1 diabetes and gestational diabetes, two areas currently understudied in the field of endocrine disruption.
I am excited to be a part of an innovative study that’s giving my team at the University of Chicago a fascinating glimpse into the relationship between insulin, sleep and body fat. We’ve been studying small biopsies of abdominal fat from volunteers who have taken part in sleep deprivation studies and are finding that when you’re sleep-deprived, you’re more likely to experience insulin resistance. This means that after you eat a meal, your body has to produce higher-than normal levels of insulin to handle the blood glucose levels in your bloodstream.
I’m collaborating on the study with Eve Van Cauter, PhD, and David Ehrmann, MD, internationally recognized researchers from the University of Chicago. Ehrmann is known for his studies on polycystic ovary syndrome, while Van Cauter conducted a range of widely published research that revealed an association between sleep deprivation and higher levels of body fat.
Normally, when insulin is released into the body, it releases a chemical that signals body cells – primarily in muscle, liver and fat tissue – to absorb glucose from the bloodstream. This process is known as insulin signaling. We’ve found that in sleep-deprived individuals, the insulin signaling process somehow goes awry, specifically at the site of fat cells.
Fat is actually your friend, but this fact gets lost sometimes in the literature. The adipose (fat) tissues are here to help you out. They’re a repository for long-term energy storage in the body. When adipose tissues can’t “do their job” and absorb blood glucose, the body senses that its own fat cells are starved for energy. It begins to resist weight loss, slowing its metabolism to conserve energy. The brain then produces chemicals leading to cravings for high-calorie foods.
Over time, insulin resistance also progresses into diabetes and heart disease, and it’s a known risk factor for breast cancer, pancreatic cancer, lymphoma, dementia, kidney disease, nerve damage and heart attack. Why sleep deprivation causes a “short” in insulin signaling remains a mystery. While the immediate solution may be obvious – get more sleep – some individuals struggle with chronic sleep disturbances, such as periodic limb movement disorder, which leads to wakefulness throughout the night. The problems can last for years despite attempts at treatment.
I’m studying the effects of various medications on insulin-resistant individuals, in hopes of finding a drug that restores the normal insulin signaling process. We’re also looking at the effects of bariatric surgery on insulin signaling. The procedure is a drastic intervention, and somewhat of a ‘last resort’ in morbidly obese people. But we know that one to two weeks after the surgery, there’s a marked improvement in the patient’s metabolic health. A lot of patients will go off their diabetes medications, including insulin, because their own insulin levels have returned to normal. The question is, how does insulin signaling change after the surgery? At this time, that’s completely unknown.
But the studies promise to shed new light on insulin signaling at the molecular level. The insulin signaling study crosses traditional boundaries of what we think of as sleep science or clinical science. It’s an exciting new frontier, and it’s been a privilege to collaborate with Dr. Van Cauter and Dr. Ehrmann.
Matthew Brady, PhD
Associate Professor of Medicine in the Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism
The University of Chicago Medicine
Dr. Brady is a published researcher widely known for his studies on metabolism, insulin and obesity. If you’re interested in being involved in a sleep study, have type 2 diabetes and are 18 years of age or older, please call the University of Chicago at 773-795-0141 for more information. This article originally appeared in the fall issue of Kovler Connection. Click here to read the newsletter in its entirity.
The University of Chicago Medical Center and the Kovler Diabetes Center are proud to support the South Side Health and Vitality Studies (SSHVS). We spoke with the Director and Principal Investigator , Stacy Tessler Lindau, MD, MAPP, to learn more about this incredible program.
What are the South Side Health and Vitality Studies?
The SSHVS are a family of inter-related studies designed by university researchers working with community leaders to produce knowledge that people can use to improve our lives, our health, and the vitality of our communities. We are focusing on generating knowledge that leverages the places that provide goods, services and jobs for the South Side and that leverages communication technology access and use.
What is the Center for Community Health and Vitality?
The Center for Community Health and Vitality (CCHV), led by Dr. Doriane Miller, works to provide community members with evidence-based knowledge about health and vitality issues prioritized by the community. The SSHVS is generating important, useful knowledge for the Center’s activities in the community.
Why are these initiatives important for the South Side of Chicago?
Chicago is one of the greatest cities in the world, with tremendous potential and will for growth. But poverty and health inequities are very real issues here that limit the ability of individuals to reach their full human potential. These initiatives complement those in other parts of our city, such as the work of west side communities with the Sinai Urban Health Institute, or the investments by the MacArthur Foundation in the Local Initiatives Support Corporation/New Communities Program. In these examples, health and community development organizations are working with other sectors, including the City leadership, to solve previously intractable problems with innovation based on evidence.
How will the CCHV and SSHVS achieve these goals?
We are part of a larger effort, the Urban Health Initiative (UHI), led by Eric Whitaker, MD, MPHExecutive Vice President, Strategic Affiliations and Associate Dean, Community-based Research. Our vision is that the South Side of Chicago will be a model of excellent urban health by 2025. We have created a working model, a playbook so to speak, for our work, called an Asset-Based Community-Engaged approach. First, before we build more or invest more, we figure out what we have. The asset census project, led by Daniel Johnson, MD and myself, takes an electron microscope approach to community assets. This project, which creates jobs for high school students and other community members, generates the most comprehensive data available about community assets. Anyone with an internet connection can use this information – and it’s already been used by more than 10,000 people for practical and research purposes. Early next year, we will launch a population health study to begin to understand what kinds and distributions of built assets appear to promote or be protective for health. In addition to research, the UHI focuses in two other areas that align with the core mission of our medical center: patient care and education. Through the SSHVS Collaborative, UHI is linking South Siders to primary care providers working together in a newly formed healthcare system. The South Side has never had a coordinated system of health care. There are also many educational initiatives, including training our medical students to work with our surrounding communities and providing incentives for promising residents from our training programs to stay and practice on the South Side.
Who is involved in these initiatives?
It’s fair to say that hundreds of people are involved in these initiatives, including university faculty, staff and students working alongside community leaders and residents. We even have faculty from other universities and leaders in the public sector working with us.
Where will these initiatives take place?
These initiatives are taking place on Chicago’s South Side, a 34 community-area region that comprises the primary service area of the medical center.
What is your role with SSHVS and its initiatives?
I am Director and Principal Investigator of the SSHVS. I lead a major component of the research and discovery for the UHI. I am also a practicing gynecologist with experience working at one of the South Side Healthcare Collaborative federally qualified health centers, university student care, and now providing care for women in our community with cancer and sexuality concerns.
How prevalent is diabetes in the South Side community?
Unfortunately, we know of no current data to answer this question. First of all, many people (perhaps as many as half) who have diabetes do not know they have it. They are undiagnosed. The best available data on diabetes prevalence come from the National Health and Nutrition Examination Survey (NHANES), but these only generalize to the level of Cook County and we have reason to believe diabetes rates may be higher here than in wealthier parts of the county. Estimates of diabetes prevalence from clinical data only tell us about the proportion of people in the health care system who have diabetes, not about those who don’t have health insurance, don’t use health care, or who have undiagnosed disease. If the South Side looks like the rest of the county or nation, rates are going up. Among older adults, rates of diabetes may be higher than 30% if we include those with undiagnosed disease.
What is SSHVS doing specifically for the diabetes community on the South Side?
Our approach has not been disease-specific. It is holistic. We are interested in knowing globally what we can do to create an environment where people are healthier and have fewer opportunities to develop disease. That being said, much of the data and work we are doing is of direct relevance to diabetes; it is a good example of a highly preventable, costly, environment-sensitive disease that could be impacted should the UHI work prove effective. We are working with diabetes experts at the Kovler Center, including Graeme Bell, PhD, Monica Peek, MD, MPH, Marshall Chin, MD, Doriane Miller, MD and others to ensure that the knowledge we generate is relevant for stemming the tide of diabetes and diabetes risk in our community.
We are providing data to the CCHV for its evidence-based programming and to other researchers and policy makers who are using the data in ways that should buffer against forces that are promoting diabetes in our community. Looking at our asset census data, we find that there are more than 8 times as many fast food restaurants as there are weight loss facilities per 10,000 population in our communities. And there are as many dialysis centers as there are weight loss facilities. How many pounds could be lost or gym memberships could be supported for the cost of just one patient per year on dialysis? This is the kind of question we have to be asking. Dialysis centers are big business and they go where the disease is. Studying the asset environment gives us empirical data about the distribution of disease in our communities.
What’s been the most interesting or challenging aspect of this initiative, for you personally?
I was at a meeting of the Robert Wood Johnson Clinical Scholars Program this week. I, along with Eric Whitaker and others working on similar efforts around the country, was a Clinical Scholar at the University of Chicago in 2000-02. The Clinical Scholars program has remained an important intellectual home and inspiration for me throughout my career. It has given me the skills and affirmed the values that make it possible to think big and to overcome institutional and societal barriers to solving big problems. At this meeting and other venues where smart people are working hard to solve health inequities and improve community health, I have realized that our biggest challenge is translation. How do we take the kind of research that gets people promoted in academe and make it align with the kind of knowledge and discovery that can transform a whole community?
There was a panel discussion at the RWJ meeting about workforce reform and what should be done to ensure that we have the right mix of people providing health care for the future. I asked the panel to imagine that a large urban community, say the South Side of Chicago, was working together toward the vision that we would become a model of excellent urban health by 2025. I asked them, based on all their work and expertise, to advise me on how we can ensure we have the right work force to provide basic health care for our 800,000 person population. The responses illustrate the challenge before us: a physician on the panel said I should look around the world (nowhere in particular), because we don’t have an answer to this question in the U.S. A medical school dean said “I applaud your megalomania.” A nurse dean emeritus on the panel pointed me toward restrictive regulation in Illinois that prevents nurses from practicing at the top of their skill set and suggested we work on changing that policy. So we have a very long way to go, not enough time, and we have to really think way outside box. I was looking for something much more concrete.
I’m a gynecologist, so I’m working beyond my formal training in asking these questions. If I don’t know something, I assume someone else does. How can we not have an answer to a community that simply wants to know how many doctors, nurses, dentists, social workers, and health outreach workers it needs to provide the basic services for its citizenship? One person commented that workforce planning is anti-American. Can we realize the vision of excellent urban health in a high poverty community without violating the basic principles of our democracy? Do we have the knowledge to do this? Are the research questions being asked at the right level with the population or the profession at the center of inquiry? These are the challenges.
We are working on launching a new cohort study in two epicenters on the South Side – one a predominantly African-American region, the other a region with a large Hispanic population. This study will provide us with the deep dive into understanding how the built assets in the community are being used to stay healthy, get healthy and manage disease and how people are using communication technology to access assets in the community or beyond. We are also hoping to collect biological information that will give us much-needed insight into the prevalence of undiagnosed disease and disease risk.
We thank Ms. Lindau for taking the time to answer our questions. To learn more about the SSHVS, please visit their website.
On behalf of the Kovler Diabetes Center, I want to congratulate Dr. Lou Philipson on a recent award he received for his contributions in diabetes research and care. Dr. Philipson, our director, was honored with the prestigious Samuel Eichold II Memorial Award last weekend during the American College of Physicians (ACP) 2011 Laureate Awards Governor’s Dinner. The award ceremony took place at Osteria Via Stato in downtown Chicago and was hosted by Dr. Jim Foody, Governor of the ACP Illinois Northern Region Chapter.
Established in 2008 in honor of the late Dr. Samuel Eichold II, the award is given to a member of the ACP or to an organization that has made important health care delivery innovations for diabetic patients resulting in improved clinical or economic outcomes; and/or a member of the ACP who has conducted research that significantly improves quality care or clinical management in diabetes.
I’m so proud to work with Dr. Philipson…an active endocrinologist, scientist and Professor of Medicine & Pediatrics. He’s also a national and international leader in diabetes care and research, specifically in supporting individuals with genetic forms of diabetes. Dr. Philipson has tirelessly explored beta-cell function for more than 25 years and is dedicated to finding new treatments for diabetes that may someday lead to a cure.
It’s a proud day for all of us at the Kovler Diabetes Center, and we applaud Dr. Philipson for this prestigious achievement.