| ...the World Health Organization has declared diabetes the health hazard for the twenty-first century. | |
| Dr. Grunberger says Michigan has a very high incidence of diabetes. |  |
| News | Contents | Wayne Medicine 1999 | Next Article | Previous Article |
| Expelling the Epidemic of Diabetes By Jeanne Fitzgerald |
There is a worldwide epidemic of diabetes, no question. Seventeen million Americans alone have it, and the disease is spreading across the globe, as our lifestyle of overeating and underexercising is embraced by citizens of other countries. In fact, the World Health Organization has declared diabetes the health hazard for the twenty-first century.
But this is not news for diabetes researchers and clinicians at the Wayne State University School of Medicine who have worked for many years on this enormously important disease. Members of the WSU faculty are recognized worldwide for their long-standing contributions in diabetic neuropathy, retinopathy, and renal and vascular complications. Even so, says John Crissman, MD, interim director of the Wayne State University Morris Hood, Jr. Comprehensive Diabetes Center, "We still need to put all the pieces together so we can take the whole spectrum of basic and clinical discoveries and translate this into clinical services to real living patients in our community."
| ...the World Health Organization has declared diabetes the health hazard for the twenty-first century. | |
| Dr. Grunberger says Michigan has a very high incidence of diabetes. | |
Community-based services for "real patients"
A real living patient with diabetes is someone who needs to be managed 24-7, meaning comprehensive care, administered not only by physicians and nurses, but dietitians, exercise physiologists, diabetes educators, and most importantly, the patient herself or himself. "This is one of the few diseases where the patient, not the doctor, is in charge," says George Grunberger, MD, professor of internal medicine, director of the Center for Molecular Medicine and Genetics, and director of The Detroit Medical Center diabetes program.
Thus, one of the goals is to offer Wayne State’s resources and expertise to physicians in the community and provide elements of diabetes management that may be impractical for community doctors to support on their own. Diabetes education for patients is an important example of this outreach. For patients to self-manage, they need to learn the correct way to eat, exercise, monitor insulin and glucose levels in the blood, and administer insulin. This work can be supported by teams of nurses, professional diabetes educators, dietitians and physicians. Such services are already provided when patients are referred to the medical center, but additional outreach programs will provide access in more communities, as well.
Wayne State is focusing on preventive medicine, especially in areas such as inner city Detroit where there is an alarming increase in diabetes among children, teenagers and adults. This increase reflects both type 1 diabetes (where the pancreatic islet cells have been destroyed and the patient must take insulin to stay alive) and type 2 diabetes (where the body is insulin resistant, but not necessarily insulin deficient). Type 1 diabetes is more prevalent in children and adolescents, whereas type 2 is more commonly found in older people. However, both kinds can appear in any age group.
Funding remains critical
Type 2 diabetes, found mostly in adults, is far more common than type 1 diabetes. About 95 percent of patients identified with diabetes have type 2. Not only is type 2 diabetes more prevalent, it is more insidious. You can have it for eight or nine years before you come to medical attention, and by then the complications have already set in.
This is why Congress and government health programs, such as Medicare, have finally begun to put their attention on and their financial clout behind diabetes. Diabetes engenders $137 billion in health care costs each year and causes 187,000 deaths. It is the leading cause of adult blindness, kidney failure, and lower limb amputations. In 1997, 27.6 percent of the Medicare budget was consumed treating diabetes and its complications.
"The good news is we can show the state and the government that we are now in a position to do something about diabetes," said Dr. Grunberger. "We can identify risk by looking at family history, maternal gestational diabetes, and ethnic background. We can treat type 2 not only with insulin, but with a variety of new oral drugs and we may even prevent it with lifestyle changes. We can address the environmental risk factors such as obesity, poor diet, and lack of exercise and intervene before it’s too late."
The newly established Wayne State University Morris Hood, Jr. Comprehensive Diabetes Center recently received $3 million from Lansing for support of diabetes programs, including screening and education for inner city minorities, mainly the African-American population whose incidence of diabetes is higher than white people. The program will also support outreach for type 1 diabetes, the principal type affecting children. Some of the state’s grant moneys are also earmarked for research.
Wayne State leaders are looking to the Michigan legislature to support their goals with insurance legislation and direct funding to provide diabetes education and pay for diabetes supplies in outreach programs. Now that Medicare is supporting diabetes education, clinicians would also like to see Medicaid pay for this very important tool. Dr. Grunberger, who is president of the American Diabetes Association--Michigan affiliate, says, "The feds knew what they were doing when they agreed to pay for education. It’s much cheaper to teach someone to take care of herself than it is to pay for a kidney transplant."
Focus on education
"The ultimate goal is to enact behavioral changes that lead to good self-management for people with diabetes," said John Waller, DrPH, professor and chair of community medicine. Dr. Waller is heading up the Community-Based Diabetes Intervention Program, which has been established to provide sustained health education programs for diabetes patients or those at risk for the disease.
Diabetes education centers are being established in faith-based organizations throughout Detroit, Mt. Clemens and Pontiac. More than 50 sites will employ community health nurses and assistants to teach patients to better manage their lifestyles and effectively reduce the effects of diabetes. The centers target at-risk populations including Hispanic, Native-American, Arab-American and African-American communities.
"This effort is important because it provides comprehensive and practical tools which attempt to improve overall health for a lifetime," said Dr. Waller.
Helping youngsters at risk for diabetes
| The Wayne State University Morris Hood, Jr. Comprehensive Diabetes Center Established in 1998, the comprehensive diabetes center will focus on research and community education and services with the goal of improving the health of Michigan’s 600,000 citizens with diabetes. Some 30 Wayne State faculty members already involved in diabetes research and care will become part of the center. New faculty in areas previously not recruited such as molecular genetics will be brought in. Basic biomedical research continues to address the genetic basis of and the disease mechanisms involved in diabetes. The university’s long-established programs in renal failure, cardiovascular disease, neuropathy and blindness will continue to grow under the center’s auspices. New efforts will be made to reach out to community physicians to provide support services for diabetes management and education. |
James Gutai, MD, professor of pediatrics, is conducting a clinical study to identify children at risk for type 1 diabetes before all the pancreatic islet cells have been destroyed. To do this, he has obtained blood samples of children whose parents and relatives have type 1 diabetes in order to detect pancreatic islet cell antibody. For individuals who are pancreatic islet cell antibody positive, he and his associates determine how much of their pancreatic function is remaining and then enter the patients in one of two ongoing, placebo-controlled studies. One group gets oral insulin to block the immune system and try to preserve pancreatic function. The other group receives very low dose subcutaneous insulin in much the same way people get allergy desensitization to see if this will prevent expression of the disease.
For children and adolescents with type 2 diabetes, Dr. Gutai is working with programs to address obesity, the primary cause of type 2 diabetes in the young.
When it comes to community-based practice, Dr. Gutai has long-standing expertise. Since 1989, he has been at the helm of a community-based program sponsored by the Fraternal Order of Masons, a private charitable organization. Working with a population of about 700 economically disenfranchised diabetic children and their families spread throughout the state, Dr. Gutai brings teams comprised of a physician, dietitian, diabetes educator, and social worker to distant areas.
"These are people who don’t have access or transportation to help them reach diabetes specialists, much less the money to pay for medical care," says Dr. Gutai. Because of the Masons, the children are seen at no cost. The sites are based in Marquette, Traverse City, Saginaw, Flint, Port Huron, Jackson and Holland. In the Holland area, many of the children are from migrant worker families of Mexican heritage. Hispanics and Native Americans have an especially high rate of diabetes, and there is believed to be a genetic component involved.
All of the physicians who send their patients to these traveling clinics received consultation notes with recommendations as to what they can be doing to enhance the therapeutic plan. In many cases, this is the first time since the children were in the hospital that they have seen a dietitian or a diabetes educator. "When you are caring for people with diabetes, the most important thing is the team approach," says Dr. Gutai. "It’s much more than prescribing insulin, which is not a cure for type 1 diabetes."
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Dr. Gutai tells seven-old Felicity Tisdale which lunchtime snacks can help control her diabetes. |
Dr. Gutai is also interested specifically in the Detroit area, where he treats the largest group of African-American children in America with type 1 diabetes. His studies compare the disease characteristics and processes of type 1 diabetes in Caucasian and African-American children.
Primary care physicians who wish to learn more about these traveling consultancies may contact Dr. Gutai’s office at (313) 745-5531.
New frontiers in diabetes research
The research realm will add enormously to the physician’s armament for treating diabetes in the next decade. Diabetes is now known to be not just one, but many diseases. What is more, it behaves differently in different people, with some susceptible to one type of complication and others vulnerable to a completely different set of factors. New strategies for treating diabetes will resemble those for treating cancer because so much more information can now be brought to the clinical management of an individual with diabetes.
Says Dr. Crissman, "We have finally managed to crack how insulin works, and what steps are necessary for insulin to work. This is the most exciting thing that has happened in diabetes research." Medical scientists at Wayne State have focused on how insulin works after it binds to its receptors and the role it plays in the process of ultimately getting glucose inside the cell where the body can use it. This is especially important in type 2 diabetes (representing 90 percent of the people with diabetes) because, although they still make insulin, it does not work effectively for them.
"It’s turning out to be more complicated every day," says Dr. Grunberger. "But we can map lots of different specific steps which get the message across. It may be a question of getting insulin to the receptor in one patient and replacing an enzyme in another. Over the next decade we foresee dozens of different drug and gene replacement therapies directed at specific problems in specific patients."
With the recent formation of the Wayne State University Morris Hood, Jr. Comprehensive Diabetes Center (see sidebar), researchers fully expect to provide the best care available for people in the Detroit area and throughout the state of Michigan. Furthermore, the center will help establish WSU and The Detroit Medical Center as pivotal leaders in the field.
Wayne State researchers attack diabetes on many fronts |
Dr. Anders Sima looks at genetic links
Genetics is turning out to be a significant issue attracting the attention of more researchers. Anders Sima, MD, PhD, professor of pathology and neurology, whose research has focused on peripheral nerve complications of diabetes, is very interested in the hereditary aspects of this problem. Dr. Sima, whose work on diabetic neuropathy is recognized worldwide, has formed a consortium with diabetes centers in Sweden and Finland.
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Dr. Sima was recently named one of the 2000 Outstanding Scientists of the 20th Century by the University of Cambridge. |
He has found certain population groups in northern Sweden and Finland, particularly, who have the world’s highest incidence of type 1 diabetes. These people, who live in isolated areas, have a relatively homogenous gene pool. Dr. Sima plans to compare genetic findings from the Finns in Finland to a large Finnish population in Michigan’s Upper Peninsula who also have a high incidence of type 1 diabetes, as well as a low incidence of intermarriage with other groups.
"This will give us a unique opportunity to study the influence of the environment on type 1 diabetes populations because they’ve been born and grown up on different sides of the planet," notes Dr. Sima. "One theory about the cause of type 1 diabetes is that it may be viral in origin. Theoretically, it could take two elements, genes and an environment factor to make the disease overt. A virus could be the "drop" that causes diabetes in people who already have a genetic predisposition."
Dr. Sima’s research efforts in peripheral neuropathy have concluded that lack of C peptide may be an important clue in solving the riddle of type 1 diabetes. C peptide rides hand in hand with insulin during the glucose metabolism process. Both are produced by the beta cells in the pancreas, and the complete lack of both causes serious neuropathologic effects in about half of type 1 diabetes patients, whose pancreatic beta cells are completely dysfunctional. Improvements in peripheral nerve complications have occurred when C peptides were given to laboratory animals with type 1 diabetes. Dr. Sima envisions a synthetic form of C peptide as a very useful potential treatment, especially in those patients who can be identified at high risk for peripheral neuropathies.
Dr. Robert N. Frank studies diabetic retinopathy
Robert N. Frank, MD, professor of ophthalmology, has studied the mechanisms of diabetic retinopathy for more than 25 years, and is considered to be among the leaders in this aspect of diabetes treatment and research. Currently, he operates a laboratory that is investigating the basic cellular mechanisms that cause diabetic retinopathy. He is also involved in three clinical trials with new drugs that offer the possiblity of stopping the progression of diabetic retinopathy. One of these drugs is a blocker for the cell membrane receptor for human growth hormone, which is thought to play an important role in the development of new blood vessels in diabetic retinopathy. These new vessels are undesirable because they can cause hemorrhages and scarring of the retina which could result in blindness.
| Dr. Frank is working with the NIH to develop a strategic plan for conquering diabetes. |  |
A related problem in diabetic retinopathy is that the cells in existing blood vessels die, causing the vessels to cease to function. Nerve cells, which receive their nutrition from blood vessels, begin to function poorly and messages are sent out to grow new vessels. Blocking human growth hormone helps with this problem, too.
Due to the effects of glucose, blood vessels in the retina of diabetic patients tend to become leaky. This in turn causes macular edema, which is the chief reason for low vision in diabetics. The nerve tissue of the macula becomes swollen with fluid, and central vision is consequently reduced. This can be treated in about 50 percent of patients with laser therapy, an area where Dr. Frank has made major contributions as well.
Dr. Frank is directing two more clinical studies which involve an inhibitor of the beta isoform of protein kinase C. This drug is also thought to prevent blood vessel growth by stopping the formation of vascular endothelial growth factor (VEGF). Interestingly, stimulation of vascular endothelial growth factor is being used for peripheral vascular and coronary artery disease, which are also commonly found in diabetes cases.
Dr. Frank encourages physicians in the community to send patients with difficult diabetes complications to Wayne State’s Kresge Eye Institute for study enrollment and for clinical management. In any case, it’s very important for people who have had type 1 diabetes for more than five years to have a complete ophthalmologic exam at least once a year, and the same can be said for type 2 diabetes.
"After about 15-20 years with diabetes, close to 100 percent of individuals with type 1 will have some form of retinopathy, and for individuals with type 2 who are on insulin therapy, about 50 to 60 percent will have retinopathy after 20 years," said Dr. Frank.
Children with type 1 diabetes are an exception. They do not tend to develop retinopathy at all until after the onset of puberty, and thus don’t need the yearly exams until that time. Dr. Frank theorizes that the upsurge of human growth hormone associated with puberty may play a role in the development of retinopathy after that time.
Pregnant women with diabetes, on the other hand, are very vulnerable to diabetic retinopathy, and it is recommended that they receive a full eye exam every trimester.
Dr. Assia Shisheva gets to the molecular level of insulin action
While physicians in the community and at research centers such as WSU continue to do a heroic job of treating and managing people with diabetes, the true solutions to the problem can only come from basic research.
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Dr. Shisheva examines the chain reactions associated with insulin release. |
This is where scientists, such as Assia Shisheva, PhD, associate professor of physiology, enter in. Dr. Shisheva, who is the recipient of numerous grants and career development awards, is examining how insulin influences the movement of glucose transporter (known as GLUT4), from the intracellular troughs to the plasma membrane. The insulin reaction is a kind of chain reaction that starts with insulin release by the pancreas and ends with glucose inside the cell. The fundamental problem in diabetes is how to put the excess glucose inside the cell where it will be broken down and not have it shuttling around in the bloodstream causing the damaging effects in diabetes. Glucose cannot penetrate the cell membrane on its own, particularly in fat and muscle tissue. GLUT4’s mission, so to speak, is to take up glucose molecules from outside the cell and put them inside the cell where the body can utilize them.
A very key finding to emerge from Dr. Shisheva’s laboratory is the fact that people with diabetes have a defective GLUT4 transport mechanism. There appears to be a problem in the signaling mechanisms of the insulin-glucose uptake chain reaction. The challenge for researchers like Dr. Shisheva is to identify which one of the many signaling elements and events this could be, which is further complicated by the fact that not all of them have even been identified yet.
The search for this mechanism has led her to another molecule, a giant molecule called p235. Dr. Shisheva is very excited about studying p235. It has been characterized as a fat and muscle enriched enzyme that generates very important signaling molecules called second messengers. These second messengers are involved in the signal transduction mechanism of many growth factors, including insulin. More importantly, the activity of this enzyme is modulated by insulin, provoking the researchers’ curiosity about what the insulin is doing there.
Wayne State University is so excited about Dr. Shisheva’s findings that they have taken out a patent on p235. "I believe p235 is important enough that it could be my lifetime research focus. Eventually, it could be a target for manipulation, resulting in relief or even cure for diabetes," she said.
Dr. Joseph Dunbar adopts novel approach
Based on years of research and a rather innovative approach to diabetes, Joseph Dunbar, PhD, professor and chair of physiology, has established a better understanding of the secondary complications of diabetes. Dr. Dunbar has documented throughout his career that hypertension and many other pathological complications associated with diabetes may be controlled through the central nervous system.
| Dr. Dunbar studies the central nervous system, which controls several complications of diabetes. |  |
Dr. Dunbar and his research associates are examining the mechanism of insulin at the peripheral level, compared to the effects of insulin in the central nervous system. "Our working hypothesis is that many of the chronic results of diabetes are mediated by the central nervous system and are the result of regulatory dysfunction," he said.
A deficiency in insulin causes metabolic changes which have many physiologic effects, including decreased blood pressure, increased vascular flows (especially in skeletal muscle), and increased sympathetic nerve activity. One of the more obvious dangers, however, is the potential damage to the regulation of the cardiovascular system. "This is critical, because as the cardiovascular system is altered by insufficient insulin, a patient’s risk for a heart attack, vascular dysfunction or stroke is greatly increased," said Dr. Dunbar.
As an extension of these studies, Dr. Dunbar is also studying the hormone leptin and its link to obesity, hyperinsulinism and hypertension--three primary complications of diabetes. Animal studies show that leptin decreases blood flow to the skeletal muscles and other parts of the vasculature, thereby increasing blood pressure and contributing to the risk for cardiovascular dangers. A clear understanding of this regulatory mechanism could potentially result in new therapies to better manage diabetes and its complications.
This very important work has been supported through the years by the National Institutes of Health, the National Science Foundation and the American Diabetes Association.
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