Engineering Hope for Diabetes

Collaborations Key at Engineering Center for Diabetes Research and Education

By Marcia Faye

Joyce Lofstrom was thirsty. Then food editor and restaurant critic for the Daily Herald newspaper, Lofstrom was conducting a restaurant review in 1978 and mentioned her insatiable thirst as of late to her lunch companion and reporter friend, Thea. “It was a cloudy day,” Lofstrom recalls. “No sunshine, just one of those winter Saturdays when you are hoping spring comes soon.” After an eighth glass still did not quench Lofstrom’ thirst, Thea urged her colleague to leave the restaurant and go to the emergency room.

National Institute of Diabetes and Digestive and Kidney Diseases cite that nearly 21 million people in the United States have diabetes mellitus, with close to one-third of this population as of yet undiagnosed. As of 2002, an additional 54 million were estimated to be pre-diabetic, with many of those expected to develop type 2 diabetes within 10 years.

Second-Century Greek Roots

Meaning “a siphon,” the word diabetes was coined by the second-century Greek physician Aretus the Cappadocian, who routinely observed one of the classic symptoms of diabetes - frequent urination - by his patients. A metabolic disorder, diabetes is the result of high levels of sugar in the blood. After food is broken down during the digestive process, sugar in the form of glucose enters the blood, becoming the main source of fuel for the body. In order for glucose to enter the cells, insulin, a hormone produced by the islet cells of the pancreas, must also be present in the blood. In a nondiabetic individual, for glucose absorption to occur, the pancreas automatically produces the correct amount of insulin. In people with diabetes, however, either little or no insulin is produced (type 1), or the body’s cells do not sufficiently respond to the insulin that is produced (type 2). The consequent build-up of sugar in the blood spills over into the urine and out of the body. A third type of diabetes, gestational diabetes, occurs in 3 to 8 percent of women during pregnancy. While gestational diabetes usually disappears after the baby is born, women with this type have a 20 to 50 percent chance of developing type 2 diabetes within five to 10 years.

Lifelong Treatment Regimen

A diagnosis of diabetes is generally made through a fasting blood glucose reading of greater than 126 mg/dc (deciliter) done on two separate occasions. Lofstrom’s visit to the ER yielded a blood glucose reading of 650; random blood glucose readings should be below 200 mg/dc. Individuals like Lofstrom with type 1 diabetes are taught to give themselves insulin, from one to four times daily. Continuous-flow insulin pumps, worn at all times, are also available; a new insulin inhaler was given FDA approval in 2006 and can replace some of the daily injections. A program of regular physical activity is prescribed, as insulin balance is achieved by food intake and daily exercise. Blood glucose levels by finger sticks must be done several times daily to ensure that sugar neither rises too high nor drops too low. Type 2 patients are not immediately prescribed insulin for their disease but a treatment plan of exercise, diet modifications, and, if needed, oral drugs that lower the amount of sugar in the blood.

Pandora’s Box of Complications

Though a veteran of the diabetes regimen of insulin dosing, Lofstrom, now a doctoral candidate at Illinois Institute of Technology and senior manager for corporate communications at the Healthcare Information and Management Systems Society, says the thought of problems arising from so many years of having the disease is never far from her mind. “Monitoring diabetes is very trying at times for me - and for my family,” she admits. “I worry about having high blood sugar so sometimes I over-amp my insulin, which results in low blood sugar.” Lofstrom credits her family for their constant support and keen observation in providing another level of checks in her proper monitoring of insulin, which she now administers via an insulin pump. They can tell by one word whether or not her levels are askew. “They know by the way I am talking that it is low. I am used to doing the finger sticks to check my blood sugar, but the worry about the long-term effects never disappears. So far, after almost 30 years with the disease, I am lucky: no complications.”

Vincent Turitto, IIT

Vincent Turitto, director of the Pritzker Institute of Biomedical Science and Engineering and chair of IIT’s Department of Biomedical Engineering (BME), understands Lofstrom’s concerns about her future. “If you don’t keep your glucose levels low, you tend to run into complications 10 or 20 years down the road,” says Turitto, whose brother has type 1 diabetes. “By not monitoring sugars well, you end up with a whole host of disorders - advanced cardiovascular disease, loss of kidney function, neuropathies, abnormal wound healing, and blindness.” Moreover, many type 2 patients develop a need for insulin injection treatment and with the growing numbers of such patients developing this disorder at earlier ages, they are likely to develop the long-term complications associated with type 1 diabetes.

First-of-Its-Kind Center

Three dimensional image of blood vessels (red) growing into a tissue engineering scaffold (white), a technique used to study wound healing processes in diabetes.
Infrared reflectance (IR) image of the region above the optic disc of a normal rat retina; the arterial and venous vessels are protruding from the optic disc.
Structure of collagen fibers in the skin of diabetic patients; the structure of the fibers is altered relative to non-diabetic patients.

IIT faculty-researchers are investigating many of the disorders associated with diabetes at the university’s Engineering Center for Diabetes Research and Education (ECDRE), the first engineering center in the nation to focus on the treatment and cure of diabetes. Formed two years ago, ECDRE is directed by Ali Cinar, vice provost for research and professor of chemical and biological engineering (ChBE). It is one of several centers under the Pritzker Institute, which seeks to develop and coordinate relationships with traditional science and engineering departments within IIT, as well as with outside institutions. The ECDRE’s collaborative relationships with various institutions, including the University of Chicago (U. of C.), a longtime leader in medical diabetes research, as well as with faculty from Armour College of Engineering, the College of Science and Letters (CSL), the Institute of Psychology, and Chicago-Kent College of Law, distinguish it as being unique in what it is able to offer.

One priority initiative being jointly investigated by ECDRE and the U. of C. is on the only “cure” currently available for type 1 diabetes patients: the development of a bioartificial pancreas through islet cell encapsulation. Naked pancreatic islet cells from two donor cadavers are injected into the patient’s liver, where they lodge in the blood vessels and respond appropriately to sugar levels. “It has been shown that patients injected with functional islet cells from cadavers will actually become insulin independent; they won’t have to inject themselves with insulin,” says Turitto. “But the long-term studies are not in yet. Some fail, some are successful. It’s not yet clear why they fail, and it’s not clear what the maximum lifespan would be.”

J. Michael Millis, University of Chicago
Photo Courtesy of U. of C. Medical Center

U. of C. surgeon Marc Garfinkel, along with Emmanuel Opara, ECDRE associate director and BME research professor, and Seda Kizilel (Ph.D. BME ’04) have already published one paper on the topic. Kizilel, now working at U. of C., is spearheading an islet project using biopolymer hydrogels-another ECDRE priority initiative-as a means of encapsulation. Garfinkel has also collaborated with BME Assistant Professor Connie Hall on blood clotting and islet cell transplantation. “As is demonstrated by these projects, the unique combination of engineering science and biologic science has tremendous potential to impact many diseases, but particularly type 1 diabetes,” notes J. Michael Millis, professor of surgery and chief of the Section of Liver Transplantation and Hepatobiliary Surgery at U. of C.

Collaborators in diabetes research, L to R: Jennifer Kang Derwent, Eric Brey and Rong Wang from IIT

Collaboration is also taking place within IIT’s traditional science community as researchers from Armour and CSL have joined to study type 1 diabetes. An interdisciplinary team that includes BME Assistant Professor Eric Brey and Jialing Xiang, assistant professor of biology, and Rong Wang, associate chair of the Department of Biological, Chemical, and Physical Sciences and associate professor of chemistry, is advancing bioartificial pancreas research through two projects: differentiating human embryonic stem cells into functional, insulin-producing islet cells and developing novel cell encapsulation methods for islet cell delivery. The project is one of nearly 30 funded by Pritzker Institute seed grants over the past two years.

Collaboration is also taking place within IIT’s traditional science community as researchers from Armour and CSL have joined to study type 1 diabetes. An interdisciplinary team that includes BME Assistant Professor Eric Brey and Jialing Xiang, assistant professor of biology, and Rong Wang, associate chair of the Department of Biological, Chemical, and Physical Sciences and associate professor of chemistry, is advancing bioartificial pancreas research through two projects: differentiating human embryonic stem cells into functional, insulin-producing islet cells and developing novel cell encapsulation methods for islet cell delivery. The project is one of nearly 30 funded by Pritzker Institute seed grants over the past two years.

Engineering and Law Collaborative

Last summer, IIT was one of five institutions selected to share a $20 million court award from the settlement of a consumer class-action lawsuit challenging the effectiveness of the diabetes drug Rezulin. The windfall benefits the Center for Diabetes Research and Policy, a collaboration of the ECDRE and two organizations within Chicago-Kent—the Institute for Science, Law, and Technology (ISLAT) and the Health and Disability Law Clinic.

“Medicine has become more and more quantitative over the past 15 years, and the reliance on disciplines such as engineering and the physical sciences has become stronger” —Vince Turitto, IIT

Directed by Lori Andrews, Distinguished Professor of Law, ISLAT undertakes research and disseminates information on the implications and applications of medical and scientific technologies within societal and legal contexts. Among the ethical issues associated with diabetes are patient privacy, intellectual property rights of patients, patents on human genes, and the funding of research and recruitment of subjects for studies. Part of the Rezulin funding will go toward developing overall policy recommendations on facilitating access to treatment, insurance coverage, and related government benefits, and to examining the conflicts that arise among competing interests of patients, diabetes researchers, research institutions, pharmaceutical companies, and the public health community. “Lori sees the value in looking at scientific research and engineering development, and matching how intellectual contributions should facilitate solutions as opposed to being barriers,” says Cinar.

Through the funding, Chicago-Kent’s Health and Disability Law Clinic, directed by Associate Professor Ed Kraus, will provide a wide spectrum of pro bono legal advocacy for its clients with diabetes and diabetes-related disabilities who are discriminated against and/or denied access to appropriate medical treatment. The award will also help to develop and support a Web-based advice center for patients and family members, giving them access to information, resources, and a guide to the various application processes necessary for acquiring benefits and treatments.

Windfall Furthers Research

Ali Cinar, IIT

According to Cinar, the funds earmarked to further diabetes research through the ECDRE are helping expand efforts in three core areas “where IIT would make its major contributions.” The first is in the continued development of biomaterials used both as hydrogel protective coverings for islet cell encapsulation and as the coating of drug-delivering microcapsules useful for patients on long-term therapy, a project being investigated by a joint IIT ChBE, Pritzker, and BME team that includes faculty members Victor Perez-Luna, Fouad Teymour, and Opara. Funding will also go toward researching biomaterials as a type of scaffolding useful in wound healing and tissue generation, spearheaded by Brey. His efforts are being combined with the use of hydrogels in the development of new tissue engineering methods for treating diabetic ulcers, peripheral vascular disease, and chronic wounds.

A second core area is the prevention of vascular complications that arise from having diabetes. “Diabetes tends to be what we call a microvascular disease,” explains Turitto. “Small vessels get injured and damaged, and actually disappear.” Cinar agrees with his colleague. “The sneaky thing with diabetes is when it starts affecting the vascular system it doesn’t start with a major artery that would be signaling early in the game that something is wrong. It will start with the tiniest vessels whose effects are not readily noticeable.” When the effects do become noticeable, however, they make themselves apparent in a devastating way. As nerves die, individuals lose their sense of cold and heat, resulting in increased chances for frostbite and burns. Wounds are slower to heal because the restorative properties of microcirculation are absent. Once the larger vessels do become affected, accelerated atherosclerosis sets in, which could result in gangrene and eventual limb amputation.

“As is demonstrated by these projects, the unique combination of engineering science and biologic science has tremendous potential to impact many diseases, but particularly type 1 diabetes,” —J. Michael Millis, University of Chicago

Vascular problems are also observed in the kidneys, where vessels narrow and become damaged. “Half of all patients on dialysis are diabetics who’ve lost kidney function,” says Turitto, noting that ECDRE faculty are working with members of the U. of C. dialysis clinic on this aspect of the diabetes problem. A final vascular complication resulting from high levels of sugar in the blood is diabetic retinopathy, or blindness. Jennifer Kang Derwent, BME associate professor, is leading a group that is measuring and analyzing variations in dynamic blood flow in the vessels of the eye, and collaborating on an ocular drug-delivery system with William Mieler, professor and chair of the Department of Ophthalmology and Visual Science at U. of C.

The third area under the ECDRE to benefit from the Rezulin award addresses the metabolic aspects of diabetes—how the body uses digested food for growth and energy—especially as it relates to obesity and type 2 diabetes. Cinar believes that education is key to one’s awareness of how diet, exercise, and possibly insulin therapy all play a role in successful diabetes management. To that end, the ECDRE is developing Web-based glucose simulators, diet-planning software, and an online food and exercise diary useful to patients and nutritionists. K–12 teachers have taken diabetes and nutrition education into their classrooms across the Chicago area in a National Science Foundation (NSF)-funded Research Experience for Teachers program where they develop a diabetes education module over a seven-week period in one of the ECDRE’s research laboratories. And for the past two summers, promising undergraduate students from IIT and around the country have participated in a NSF-funded program that paired them with ECDRE mentors working on various diabetes-related projects.

From Collaboration Comes Hop

With a solid base in Armour College of Engineering and through interdisciplinary, collaborative relationships with law, the sciences, and medicine—the ECDRE is positioned to make substantial contributions to diabetes research and education, now and in the years to come. The partnership between IIT and the U. of C. is one that is mutually beneficial, allowing for opportunities that may not be possible if each institution were working alone. “Establishing key partnerships with our engineering colleagues at IIT will allow us to explore enabling technologies that merge molecular biology with biomedical engineering science,” says Jeffrey B. Matthews, Dallas B. Phemister Professor and chair of the U. of C. Department of Surgery. “Such efforts create a unique synergy in which new approaches to surgical treatments can be realized and in which novel lines of inquiry can be developed.”

As fields such as medicine evolve and expand in uncharted directions, the opportunity for mutually beneficial partnerships develops. “Medicine has become more and more quantitative over the past 15 years, and the reliance on disciplines such as engineering and the physical sciences has become stronger as the need for new techniques and devices arise to better detect, treat, and help cure disease,” says Turitto. “Biomedical engineering promises to change the practice of medicine in the coming century much as traditional engineering sciences have changed our society over the past 100 years.”

www.ecdre.iit.edu


A Unique Approach to the Diabetes Solution

Rong Wang [see article] believes the diabetes effort on which she is collaborating is unique, in part because of contributions being made by the interdisciplinary team of IIT biologists, chemists, biomedical engineers, and mechanical engineers. All will be indispensable in helping to accomplish the project’s early two goals: the differentiation of human embryonic stem cells into functional pancreatic islet cells and the development of novel cell encapsulation technologies for cell delivery to effectively reduce or eliminate the patient’s rejection of the cells, a problem commonly encountered in currently existing stem cell therapies.

“The growth of stem cells in the human body relies on a micro-environment, so-called physiological niches, within the tissue,” explains Wang. “The tissue is actually exerting forces to the cell; the cell receives the signal, which significantly impacts the decision-making along a certain differentiation path.” One task for Wang’s interdisciplinary team is to prepare just the right tissue substrate for differentiation to occur. “Engineers know how to manipulate materials to make this structure,” she says, “and scientists determine what that material should be.” Wang acknowledges that many challenges need to be addressed, including how to control cellular growth to prevent tumor formation and determining the best method for islet cell delivery, but is confident her collaborative team is well-equipped to find solutions.

“We need the scientists and the engineers working together,” she says. “I feel that it’s really important.”