Media contact: Tom Hughes, (919) 966-6047, tahughes@unch.unc.edu

Wednesday, May 8, 2013

CHAPEL HILL, N.C. - The Patient-Centered Outcomes Research Institute (PCORI) has approved a research award to the University of North Carolina School of Medicine to study the role of glucose monitoring in patients with type 2 diabetes using oral medications. The three-year project will focus on assessing the impact of three different types of blood sugar or glucose home testing approaches on outcomes important to patients with type 2 diabetes treated in a community-based clinic setting.

Katrina Donahue, MD, MPH, associate professor of family medicine, and Laura Young, MD, PhD, assistant professor of medicine, will lead the research project. Both are members of the North Carolina Clinical and Translational Institute, academic home of the National Institute of Health’s Clinical and Translational Science Awards (CTSA). John Buse, MD, PhD, professor of medicine and deputy director of the CTSA, will lead the stakeholder advisory team comprising patients and community members as well as representatives from industry, advocacy groups and state government. The contract from PCORI is for $2,090,699.80.

“Given the time and resource-intensive nature of glucose self-monitoring, to test or not to test is a critically important question facing the millions of patients living with non-insulin-treated type 2 diabetes,” said study leaders Drs. Donahue and Young in a written statement. “Patients often receive mixed messages about blood glucose self-monitoring. We are excited that PCORI has recognized the lack of consensus around the utility of glucose monitoring in patients with type 2 diabetes not treated with insulin.”

The researchers stated that this important, patient-centered project will help patients and those that care for them make better, evidence-based decisions about whether or not blood glucose monitoring can improve the outcomes  they value most. They also said that the results will shape future decision-making in diabetes-care practice and guidelines.

The study is part of a portfolio of patient-centered research that addresses PCORI’s national research priorities and will provide patients with information that will help them make better informed decisions about their care.

UNC is well placed to manage the study because of the collaborative network and research infrastructure provided by the NIH CTSA as well as UNC’s well-known work in the area of patient-centered care. Dr. Donahue practices in the UNC Family Medicine Center, an NCQA-certified Patient Centered Medical Home. Study participants will come from counties in central North Carolina, through partnerships with the UNC Physician Network practices.

The UNC study is one of 51 projects totaling more than $88.5 million approved for funding by PCORI’s Board of Governors on May 6. All were selected through a highly competitive review process in which scientists, patients, caregivers, and other stakeholders helped to evaluate more than 400 applications for funding. Proposals were evaluated on the basis of scientific merit, how well they engage patients and other stakeholders, their methodological rigor, and how well they fit within PCORI’s national research priorities.

The awards are part of PCORI’s second cycle of primary research funding. This new round of funding follows PCORI’s initial approval of $40.7 million in support for 25 projects under the institute’s national research priorities. All awards in this most recent round of funding were approved pending completion of a business and programmatic review by PCORI staff and issuance of a formal award contract.

For more information about PCORI’s Funding Announcements, visit www.pcori.org/funding-opportunities.

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About PCORI

The Patient-Centered Outcomes Research Institute (PCORI) is an independent, non-profit organization authorized by Congress in 2010. Its mission is to fund research that will provide patients, their caregivers and clinicians with the evidence-based information needed to make better-informed health care decisions. PCORI is committed to continuously seeking input from a broad range of stakeholders to guide its work. More information is available at www.pcori.org.

About NC TraCS/UNC CTSA

The North Carolina Translational and Clinical Sciences (NC TraCS) Institute, the integrated home of the Clinical and Translational Science Awards (CTSA) program at UNC-CH, is supported through the National Institutes of Health (NIH), grant ULTR000083. The CTSA program is led by the NIH’s National Center for Advancing Translational Sciences (NCATS).

Read the article online.

John B. Buse, MD, PhD, division chief of endocrinology and metabolism in the University of North Carolina School of Medicine and director of the UNC Diabetes Care Center, is one of five international leaders in the field of diabetes research who will comprise the Selection Jury that will select the first-ever Prize Laureate of the Harold Hamm International Prize for Biomedical Research in Diabetes.

In conjunction with World Diabetes Day on November 14th, the Harold Hamm Diabetes Center at the University of Oklahoma held a news conference to publicly announce the names of the Selection Jury. The announcement was made by Dr. Timothy Lyons, chair of the Prize Selection Jury.  

The 2013 Selection Jury is composed of:

• John Buse, MD, PhD, CDE - University of North Carolina School of Medicine
• Edwin Gale, MD - University of Bristol, United Kingdom
• Barbara Howard, PhD – MedStar Health Research Institute
• Paul Robertson, MD – University of Washington
• Charles Stanley, MD - University of Pennsylvania Perelman School of Medicine

For more information, please visit haroldhammprize.org.

“Both of these agents are very exciting diabetes products and really good blood sugar-lowering drugs,” said John B. Buse, MD, PhD, first author of the study, division chief of endocrinology and metabolism in the University of North Carolina School of Medicine, director of the UNC Diabetes Care Center and a a PI Extender of the UNC NIH Clinical and Translational Science Awards (CTSA).

“The results of this study will be helpful to both doctors and patients in shared decision-making about which of these two drugs is better suited for a particular patient.”

“The results of this study will be helpful to both doctors and patients in shared decision-making about which of these two drugs is better suited for a particular patient,” Buse said. “For example, for some patients the additional weight loss advantage provided by liraglutide might tip the scales in favor of that drug. For other patients, though, the greater convenience of once-weekly injections and the more favorable side effects profile of exenatide would be extremely appealing.”

Results of the study were published online first ahead of print on Nov. 7, 2012 by The Lancet.

In the study, 912 patients from 105 sites in 19 countries were randomized to receive injections of once-daily liraglutide or once-weekly exenatide for 26 weeks. The primary endpoint of the study was the overall reduction in HbA1c (blood sugar) levels from baseline to 26 weeks.

Both drugs produced a clinically significant decrease in blood sugar levels. By the end of the study, 60 percent of the patients taking liraglutide had achieved HbA1c levels of less than 7 percent, vs. 53 percent of patients on exenatide. Both drugs also produced progressive decreases in bodyweight, but patients taking liraglutide lost about 2 pounds more weight than those on exenatide.

Patients in both groups reported having side effects on occasions over the six month trial. The most common were nausea (21 percent in the liraglutide group vs. 9 percent in the exenatide group), diarrhea (13 percent vs. 6 percent) and vomiting (11 percent vs. 4 percent). The occurrence of side effects lessened in both groups over time. Five percent of patients on liraglutide and 3 percent on exenatide dropped out of the study because of side effects.

The study was funded by Eli Lilly and Amylin Pharmaceuticals. Amylin is the manufacturer of Bydureon, the exenatide preparation that was used in this study.

In addition to Dr. Buse, other authors were Michael Nauck, Thomas Forst, Wayne H-H Sheu, Sylvia K. Shenouda, Cory R. Heilmann, Byron J. Hoogwerf, Aijun Gao, Marilyn K. Boardman, Mark Fineman,  Lisa Porter and Guntram Schemthaner.

• Gynecology - #34
• Ear, Nose & Throat - #42
• Cancer, #43

Additionally, the following specialty areas at UNC Hospitals were designated by U.S. News as “high performing,” representing the top 25 percent of hospitals in their specialty nationally.

• Cardiology & Heart Surgery
• Diabetes & Endocrinology
• Gastroenterology
• Geriatrics
• Nephrology
• Neurology & Neurosurgery
• Pulmonology
• Urology

This is the 20th year in a row that multiple specialties at UNC Hospitals have been included in U.S. News & World Report Best Hospitals list. Only 3 percent of hospitals in the United States meet the U.S. News Best Hospitals criteria.

The U.S. News rankings are just one measure of success. UNC's most recent awards and honors can be viewed here.

Thursday, July 5, 2012

CHAPEL HILL, NC – Scientists at the University of North Carolina School of Medicine have used injections of antibodies to rapidly reverse the onset of Type I diabetes in mice genetically bred to develop the disease. Moreover, just two injections maintained disease remission indefinitely without harming the immune system.

The findings, published online ahead of print (June 29, 2012) in the journal Diabetes, suggest for the first time that using a short course of immunotherapy may someday be of value for reversing the onset of Type I diabetes in recently diagnosed people. This form of diabetes, formerly known as insulin-dependent diabetes mellitus, is an autoimmune disease in which the body’s own immune T cells target and destroy insulin-producing beta cells in the pancreas.

The immune system consists of T cells that are required for maintaining immunity against different bacterial and viral pathogens. In people who develop Type 1 diabetes, “autoreactive” T cells that actively destroy beta cells are not kept in check as they are in healthy people.

Senior study author Roland Tisch, PhD, professor of microbiology and immunology at UNC, said a need for effective immunotherapies also exists to treat Type 1 diabetes in people already living with the disease.

“Clinically, there have been some promising results using so-called depleting antibodies in recently diagnosed Type 1 diabetic patients, but the disease process is blocked for only a short period of time,” Tisch said. “These antibodies don’t discriminate between T cells normally required for maintaining immunity to disease-causing pathogens and the autoreactive T cells. Therefore T cells involved in maintaining normal immune function are also going to be depleted.

“You’re getting some efficacy from immunotherapy but its only transient, it doesn’t reverse the disease, and there are various complications associated with the use of these depleting antibodies.”

Tisch said his UNC lab has been studying the use of certain “non-depleting antibodies.” These bind to particular proteins known as CD4 and CD8 expressed by all T cells. Just as the name implies, when these non-depleting antibodies selectively bind to CD4 and CD8 they don’t destroy the T cells; the overall numbers of T cells are unaffected.

With this in mind Tisch wanted to determine whether these non-depleting antibodies could have a therapeutic effect in the non-obese diabetic, or NOD mouse, an excellent model for human Type 1 diabetes.

The answer is yes. In some of the recently diagnosed NOD mice, blood sugar levels returned to normal within 48 hours of treatment. Within five days, about 80 percent of the animals had undergone diabetes remission, reversal of clinical diabetes.

“The protective effect is very rapid, and once established, is long-term,” he said.  “We followed the animals in excess of 400 days after the two antibody treatments, and the majority remained free of diabetes. And although the antibodies are cleared from within the animals in 2-3 weeks after treatment, the protective effect persists.” The study showed that beta cells in the NOD mice had been rescued from ongoing autoimmune destruction.

In looking for the mechanism to explain how the therapy worked, the researchers found that the antibodies had a very selective effect on T cells that mediated beta cell destruction. After treatment, “all the T cells that we would normally see in the pancreas or in tissues associated with the pancreas had been purged,” said Tisch. This despite the fact that the numbers of T cells found in other tissues and blood were unaffected.

The researchers also found an increase in the numbers of “immune regulatory” T cells. In the healthy individual, these regulatory T cells block autoimmunity, Tisch explained. “They protect us from the autoreactive cells that all of us have. And that’s why most of us don’t develop autoimmune diseases such as Type 1 diabetes.”

“We’ve demonstrated that the use of non-depleting antibodies is very robust. We’re now generating and plan to test antibodies that are specific for the human version of the CD4 and CD8 molecules.”

UNC study coauthors with Tisch are first-author, Zuoan Yi, (now at the University of Iowa); Ramiro Diz, Aaron Martin, Yves Maurice Morillon, Douglas E. Kline, (now at the University of Chicago); Li Li (now at Harvard Medical School); and Bo Wang.

Support for research came from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health; and from the Juvenile Diabetes Research Foundation.

The never-ending controversy regarding Avandia persists despite another set of hearings.  The two most important findings of the panel of thirty three members were decided in a complex series of votes.  First,  nearly 60 percent of panelists felt that there were safer alternatives to Avandia, even from the same class.  More importantly, about 90 percent of panelists felt that Avandia should either be withdrawn or that additional warnings and/or restrictions should be added to its labeling for use.  To be fair, only a third felt the drug should be withdrawn.

This panel is advisory to the FDA.  To me, the overriding question for the FDA is whether they are restricted to decision-making clearly supported by impeccable science or are they expected to err on the side of protecting the well-being of all Americans.  We have no proof or even very strong evidence that Avandia is unsafe.  That said, there is absolute clarity that Avandia has disadvantages with respect to cholesterol levels in head-to-head comparisons with the other drug from the same class and substantial circumstantial evidence that Avandia’s disadvantages may extend to heart attack and other cardiovascular problems.  If there is another agent with lesser safety concerns, should the FDA demand that Avandia be withdrawn?  Is that fair?  But, is fairness to industry a compelling issue in regulating drug safety?  A decision to seek the withdrawal of Avandia would break new ground for the agency.  This would be met with cheers by some and absolute horror by others.  Frankly, I do not know what the correct response of the agency should be.

But, as a physician and as a member of a profession, it is inconceivable to me that anyone would make a conscious decision to prescribe Avandia today.  I am not terribly worried about the safety implications of a new prescription for Avandia for the patient.  But, I am worried for the prescriber.  Every day about a thousand people with diabetes have heart attacks and close to 500 die of complications of vascular disease – - whether they are treated with Avandia or not.  If they were taking Avandia, it seems reasonably likely that someone will raise the issue if malpractice was involved in prescribing Avandia.  I fear for doctors that prescribe Avandia, not because they are guilty of malpractice, but because someone may raise the issue and instantly and substantially complicate their lives.  There are alternatives to Avandia where lesser safety concerns exist.  If providers did not prescribe Avandia, there would be no reason for the FDA to ask for its withdrawal.  So every health care provider effectively faces the same decision as the FDA does.

Most unfortunately, the Avandia controversy has been a huge distraction for the entire pharmaceutical industry, health care providers, patients, regulatory bodies, the media, et cetera.  We could have all put our time to so much better use such as developing consensus about how to tackle the much bigger problem of prevention of diabetes.  Consider for a moment the manufacturer.  By continuing to market this hobbled product, are they diminished?  Does the sheer effort of defending the drug prevent the company from performing as well in other areas?  Does the venom of those that attack Avandia poison present or future opportunities for the company and the industry in general?  The answer to those questions seems clear to me.  A business decision by the company to voluntarily withdraw the drug, keeping it available in a compassionate use program for those with a compelling indication, would neither be an admission of guilt nor abandonment of its supporters.

The fundamental problem is that despite over ten years of questions regarding potential cardiovascular risk associated with Avandia, a definitive answer has not been provided.  The clearest message from this entire process is that companies must embrace those that raise issues regarding safety and conduct impeccably designed studies to address concerns in order to control their own destiny.   These are multi-billion dollar markets that can support great science to address important issues.

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• Top physicians, diabetes educators, foot specialists
• Health Fair showcasing state-of-the-art technologies and advances in diabetes care
• Variety of afternoon workshop topics
• Opportunities to speak one-on-one with diabetes care experts
• Physical activities for everyone
• Healthy snack & sit down banquet lunch provided
   

Please click here for more information and to register.

• Click here to go back to May 13 Vital Signs

• View the Vital Signs archives

• Top physicians, diabetes educators, foot specialists
• Health Fair showcasing state-of-the-art technologies and advances in diabetes care
• Variety of afternoon workshop topics
• Opportunities to speak one-on-one with diabetes care experts
• Physical activities for everyone
• Healthy snack & sit down banquet lunch provided
   

Please click here for more information and to register.

• Click here to go back to May 13 Vital Signs

• View the Vital Signs archives