Summary of Diabetes Research Institute's 6th Annual Research Update ("Roadmap to a Cure")

On Saturday, I attended the Diabetes Research Institute's Sixth Annual Research Update ("Roadmap to a Cure") in New York. This event has become an annual highlight in terms of updating the lay audience on progress made in type 1 diabetes research, and I highly recommend that anyone in the Northeast (or nationwide, if they care to trek into New York) attend if they are interested in what type of cure-related research is actually being undertaken right now.

Since its inception, the event has been held at the Grand Hyatt New York Hotel, which is located right next to Grand Central Terminal. The first half of the morning involves everyone, with about 3-4 presentations from DRI researchers or colleagues and affiliates from around the world. The day is broken with a sit-down meal at midday, followed by several "break out" sessions in the afternoon, including an opportunity for the audience to ask questions of the research panel.

This year, the most consistent theme I saw was that almost all of the presentations noted the recent but growing body evidence which suggests that type 1 diabetes is not a one-way street to the total elimination of beta cells by a t-cell autoimmune mechanism.

As some people may recall, it wasn't until researchers lead by Dr. Peter Butler from UCLA presented his groundbreaking results at the 65th ADA Scientific Sessions in San Diego during 2005 that decades of established scientific dogma was first disputed. Prior to that, the accepted and prevailing belief was that people receive all the beta cells they are ever going to have at birth, and that once the immune system destroys them, they are gone forever. Subsequent to Dr. Butler's groundbreaking study on just 42 patients, several prominent researchers have successfully replicated those findings, adding to its credibility. For example, at the 66th ADA Scientific Sessions in Washington D.C. this year, Joslin researchers revealed that they had examined 326 of their type 1 diabetes "medalists" and they also found evidence of positive C peptide among a number of long-standing (50+ years) type 1 patients.

Naturally, diabetes clinicians like to speculate that that good "control" helps preserve the life of the remaining islets, but the fact is that this remains an unproven assumption, although its certainly a logical assumption. However, its worth noting that some of the long-term Joslin medalists were diagnosed at a time where it was not even possible to do home blood glucose testing and A1C tests did not even exist. Although these patients are in good control by today's standards, they may not have had the degree of control they enjoy today back when they were first diagnosed.

Because of this evidence, the question of whether beta cell regeneration is a possible approach to a cure is an area of tremendous interest among researchers. I believe the presentations from University of Miami's Dr. Norma S. Kenyon, PhD, an immunologist who has spoken at several previous updates (her own daughter has type 1 diabetes, so she has a special interest in the field) as well as a colleague from University of Virginia who gave a very informative presentation covered this best. The general consensus among the entire research panel was that a "cure" will almost assuredly require a combination therapy, with one treatment to address the issue of autoimmune response, and another to restore euglycemia since a majority of patients with type 1 diabetes (even those with positive C peptide levels) do not have sufficient beta cell mass necessary to restore the patient to insulin independence. While some people speculate that may not be necessary once the issue of autoimmunity is addressed, there is little clinical evidence to back the theory up. Anyway, the area that seems most likely to address this in the near future is islet transplantation, and researchers are examining a variety of approaches, ranging from xenotransplantation to tissue engineering in an effort to work around the shortage of transplantable islets. One presenter (I believe Dr. Skyler) noted that perhaps the U.S. should consider an approach similar to what is now used in the Netherlands, which is that unless someone specifically says they do not wish to be an organ donor, their organs will automatically be included among those eligible for transplantation when they die. Its a thought worth considering given that 18 people die each day waiting for organ transplants, and this number could be reduced to virtually nothing if we adopted the sytem used in Holland.

Stem cell research was discussed, and as Dr. Juan Dominguez-Bendala, PhD eloquently noted in his presentation, it is a very new field, so researchers are kind of learning as they go along. The idea of using stem cell research to create an endless supply of customized beta cells for transplant seems unlikely to emerge within the next few years because of some concerns about potential tumors which might be caused from repeated use of the same stem cells to "manufacture" beta cells for transplanation. But the field does look promising as a potential source down the road, and because science is incremental, we should continue to pursue it as a possible means to advance treatments for people in the future.

Another researcher, Cherie Stabler, PhD, from Emory University School of Medicine spoke on their efforts in the field of tissue engineering. She discussed several approaches that are now being pursued, and the hopes as well as the challenges associated with each approach. It was informative, but also highlighted the issues that researchers are running into, thus providing a balanced perspective on the subject.

Perhaps the most interesting take-away was a fairly recent discovery on the benefit of exenatide (better known by its brand name Byetta). There is currently a lot of buzz about this medicine for patients with type 2 diabetes, but I was surprised to learn that it may also be useful for patients with type 1 diabetes because this drug appears to increase beta cell mass. Therefore, assuming that researchers can successfully address the ongoing beta cell attack by the body's immune system, for patients who do have a positive C peptide, the use of Byetta could help in expanding their remaining beta cell mass. A pending human clinical trial among recently diagnosed patients will experiment with some antibodies to arrest the autoimmune attack, combined with treatment with Byetta in an effort to expand the remaining beta cells. The idea is that research has already proven that retaining beta cell function greatly assists in managing blood glucose levels, it reduces the incidence of hypoglycemia, and minimizes exogenous insulin that is required to manage their diabetes.

I asked Dr. Kenyon about the DRI's recent finding that questions the validity of using the NOD mouse as the animal model for research. She noted that while the islet structure in mice is quite different, the mouse model remains useful in research to test theories and concepts, but that using other animal models such as the cat might be required. Interestingly, I recently spoke with Todd Zion, the CEO of SmartCells, Inc. and he also mentioned that they were using cat models and found them to be useful in their research as well. I will elaborate on that conversation in a future blog entry.

Well, thats the quick summary. I did ask if they would be willing to publish the researchers' presentations on the DRI website, and it does appear that they have taken my suggestion seriously, because their website indicates they will be summarizing the presentations in the near future. See http://www.diabetesresearch.org/Foundation/RegionalOffices/Northeast/RecentEvents/newyorkresearchupdate.htm for details.