2005 Wrap-Up and Outlook for 2006

Happy New Year! I cannot think of a better opportunity to summarize the world of diabetes research (as I see it, anyway) during the past year, and offer some insight into what 2006 most likely holds in store. One of the most noteworthy events was the closure of DiabetesPortal.com and its related websites. While I understand my friend Deb Butterfield's decision (she adopted a second child and wanted to dedicate more time to her family), without a doubt, the online community she established was impacted by the decision. Fortunately, I have found an alternative that is neither littered with propaganda from the likes of a pharmaceutical company, nor contains rhetorical gibberish and innuendo about how to live with diabetes from organizations like the American Diabetes Association. Most notable among these sites is DiabetesTalkFest.com, an online community managed entirely by volunteers who live with diabetes themselves, and therefore have no agenda other than to facilitate community service!

To be sure, 2005 did not deliver the long-promised cure patients with diabetes would have liked to see. One can make a fairly convincing argument that overall scientific priority regarding diabetes research remains disproportionately allocated towards maintaining the status quo of keeping diabetes as a chronic illness with treatment for diabetes symptoms rather than eradicating the disease itself. Dollars speak volumes here, and while JDRF announced its 2006 goal of raising $1 billion per year (nearly 90% of which will be channeled directly into research) when compared to the hundreds of billions of dollars that the pharmaceutical industry alone spends on research for diabetes treatments (most of which target treatments for type 2 diabetes exclusively), a change in research prioritization would seem appropriate.

Evidence-based medicine is founded on the belief that a finding must be reproducible to be believable, but one of medicine's most overlooked problems is the fact that some questions keep being asked over and over. Nowhere is this more evident than in the field of diabetes research. The Diabetes Complications and Control Trial (DCCT) was supposed to be the definitive answer to the question of whether maintaining non-diabetic blood glucose levels could reduce the likelihood of a host of different complications. Yet since the conclusion of the DCCT, researchers have continued to ask the same (or similar) questions. The UK Perspective Study, for example, was essentially a repeat of the DCCT, only examining Type 2 patients exclusively, rather than patients with Type 1.

An article published last month in The New England Journal of Medicine featured yet another a follow-up report on the original DCCT showing that intensive control yields definitive proof of cardiovascular benefit, including statistically significant reductions in both heart attacks and strokes. However, if patients could always maintain ideal blood glucose levels, it would be similar to not being a diabetic, so isn't it obvious that doing so reduces (but unfortunately does not eliminate) complications, including cardiovascular damage? As anyone with diabetes knows, it is virtually impossible to always maintain euglycemic blood glucose levels with current treatments. While the recent study resolves a long-outstanding question that the original DCCT never answered, the latest study seems more like a complete waste of time, effort and money than it does "groundbreaking" research as it was hailed by Robert Rizza, President of the American Diabetes Association. Hopefully now that this question has finally been put to rest, perhaps now clinicians will finally begin in earnest to address the serious limitations of current treatments rather trying to prove whether intensive control is beneficial for our health.

Fortunately, some medical experts have finally started to ask: "What part of 'yes' don't doctors understand?" A well-written article in the Monday, January 2, 2006 edition of The Washington Post highlighted this issue. Perhaps a change in philosophy will encourage doctors to start examining the limitations of current forms of treatment. Doctors must still address the reasons that 4 out of 10 patients with diabetes do not test as often as they recommend, or why less than 12% of people with diagnosed diabetes meet the recommended goals for blood glucose levels according to a study published in the January 21, 2004 issue of the Journal of the American Medical Association. Last summer, the British medical journal The Lancet announced that it would now require that authors submitting papers show they performed a meta-analysis of previous research or consulted an existing study. We should expect to see other scientific journals, perhaps even The New England Journal of Medicine, implement similar requirements in the future. This may be the impetus needed to encourage vital changes!

Ironically, considerably less press attention was given to the fact that one of the DCCT's (and the follow-up cardiovascular study's) investigators, Dr. David Nathan, will be the Principal Investigator of a fundamentally new human clinical trial on a potential treatment to address the issue of autoimmunity that causes type 1 diabetes. That trial is expected to begin this summer. The Phase I human clinical trial will test one part of a two-part therapy to specifically eliminate the T cells that incorrectly destroy the islet cells and causes diabetes. The Iacocca foundation quietly announced last fall that thanks largely to a generous contribution from DaimlerChrysler in exchange for Mr. Iacocca's appearance in some TV spots for Chrysler last year, the "Join Lee Now" initiative had surpassed its halfway mark of raising $11.5 million (as of January 2006, the initiative had over $9 million in commitments), which is more than sufficient to begin human clinical trials in 2006. Given that Dr. Faustman's research has unintentionally become so popular among many families impacted by juvenile diabetes, keeping the publicity to a minimum would seem appropriate, but nevertheless, the fact remains that human trials will begin sometime this year! A much more detailed update on this trial can be found at the JoinLeeNow.com website, although I found a more informative article within the "JoinLeeNow.com" website which you can read here: Chronicle of Philanthropy article.

During the past several weeks, we have also been deluged by the unfortunate news of fraud related to the pioneering stem-cell research conducted by South Korea's Dr. Hwang Woo Suk. While unfortunate, I am quite optimistic that it will not seriously damage the long-term outlook for stem cell research. One reason for my feelings is that by removing the "hype" the focus can go back to the basics of research. In late 2004, voters in California, frustrated by the Bush Administration's policies equating cell-based research with abortion, took matters into their own hands. California voters approved a measure to apply $3 billion in state funds over the next decade to support embryonic stem cell research, creating the largest state-supported scientific research program in U.S. history. Connecticut, New Jersey and Illinois have since followed suit, so significant U.S. research dollars are now flowing into the field of stem cell research, and progress is likely to come from research that is conducted right here in the U.S. Ongoing progress is reported in another blog called The California Stem Cell Report. Another very recent development is the fact that scientists at a laboratory affiliated with the University of Wisconsin-Madison just reported they developed a stem cell culture medium that is free of animal cells and used it to derive two new human embryonic stem cell lines, which represents a significant breakthrough in the field. More progress is likely to come during the next year, albeit at a slower pace than we had come to expect resulting from Dr. Woo Suk's research, which seemed more focused on turning the researchers into international celebrities in the field rather than on the basics of scientific research.

Another rather quiet announcement made just before the New Year was JDRF's appointment of Arnold W. Donald as the organization's new CEO. Personally, I hope that Mr. Arnold will push JDRF further beyond islet transplantation and stem cell research, which were treatment protocols that his predecessor Mr. Van Etten pushed so forcefully under his leadership. Don't get me wrong, I have no problem with pursuing islet transplantation, but I don't like to see it come at the expense of other promising avenues. JDRF quietly began pursuing areas beyond islet transplantation in recent years (looking into islet regeneration, for example) with small, special funding projects. This is kind of an acknowledgment of the apparent limitations of islet transplantation, and the fact that there may be other promising approaches to curing diabetes. Perhaps the new CEO will push down this path even further, although the peer review and lay review organizations with JDRF will ensure that the JDRF will take measured movements regardless of the CEO's direction. I am saving my judgment on Mr. Arnold's appointment until I see exactly what direction he plans to take JDRF, but the change is likely to be positive for the world's leading diabetes research organization.

On the treatment front, we can expect to see complete analysis published on the clinical trials conducted during 2004-2005 for the Islet Neogenesis (new birth) Associated Protein (better known as INGAP). For more information, please see: http://www.dif.org/n_articles/IsletRegeneration.html for more complete details on where this research stands at the present time. While it is unclear at present whether INGAP will itself ever become a treatment for people with type 1 diabetes, the knowledge gained from islet regeneration will nevertheless prove extremely valuable (for such fields as islet transplantation or to restore faulty hypoglycemia counterregulation for patients with type 1 diabetes) regardless of whether it works as a stand-alone treatment for type 1 diabetes. By the way, if you aren't familiar with INGAP, the story has been chronicled over the last several years. To read the story as it has unfolded, please see the following links:

Spring 2002
Winter 2002
Summer 2003
Spring 2004

Elsewhere on the treatment front, a biotech startup company called Smart Cells, Inc. that I called attention to last year has continued to receive investor backing and thus far, its nanotechnology solution to the issue of insulin dosage challenge continues to look very promising in pre-clinical trials. Essentially, the company's form of insulin, if it continues on its thus-far successful path, will release insulin molecules in direct proportion to a patient's blood glucose levels, eliminating the nasty side-effect of hypo or hyperglycemia caused by all current forms of insulin. The NIH/NIDDK is perhaps one of the company's biggest "investors", but a noteworthy investment from and advisory services being provided by Novo-Nordisk A/S may help the Danish pharmaceutical company widen its recently won market share leadership in the U.S. insulin market over rival Eli Lilly & Co. (see my previous post) for details.