We've long heard the theory of a possible cause for type 1 diabetes being that beta cells die off. Or in the case of type 2, that beta cells are simply getting a little overworked and resistant and just can't keep up with their task of insulin-making.
Hey, we know that research story well (maybe not as well as the hundreds upon hundreds of lab mice that have been cured, of course).
But now, there's a new theory being explored that could make us rethink the "beta cell death" train of thought we've come to know so well.
The JDRF and Michigan-based Brehm Center for Diabetes Research have announced a new two-year partnership aimed at exploring how beta cells might not actually be dying off, but rather may be regressing to an immature state and losing the ability to produce insulin. Basically, they're reverting back to the Baby Beta Cell stage when they weren't grown up enough to do what they're supposed to.
JDRF is putting up $1 million for this partnership, and those involved in the research believe it could "change our basic understanding of the disease and lead to novel preventative and restoration therapies."
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The JDRF's national media relations manager Tara Wilcox-Ghanoonparvar tells us that this isn't a "shift" in focus for the JDRF, but rather another part of its ongoing Regeneration Program that's long been in place. "This work will look at a relatively under-studied mechanism of beta cell loss (de-differentiation), determine its relevance to T1D development and begin to explore mechanisms that could be exploited therapeutically to intervene. It is a new pathway to achieve beta cell regeneration, and we are pursuing several lines of research in parallel towards this broad goal," she said.
As to the so-called "immature beta cell" (de-differentiation) theory itself, Dr. Domenico Accili who's director of the Columbia University Diabetes and Endocrinology Research Center in New York City published a paper on this topic in 2013; it's one of the foundations of this research, along with other scientific observations in the D-research community, the experts tell us.
You may remember that we at the 'Mine introduced you to the folks at Brehm back in September 2012, when my mom was taking part in a clinical study there and I got to go with her for a sneak peek inside the impressive state-of-the-art facility located on the University of Michigan campus. Now in its 10th year of operation, the Brehm Center takes it's name from donors Bill and Dee Brehm (Dee being a type 1 diagnosed back in 1949 when she was 19!). This D-research hub is making some pretty significant strides, especially with its 2007-created Coalition that includes nine scientists from eight different universities across the U.S.
"The Brehms actually had this idea of forming... a sort of a dream team of scientists who would work as if they were all co-located, except they wouldn't be," Brehm Center director Dorene Markel said. "It was formed to really have a team of scientists who would work together in a way that really had not happened in diabetes research before."
Another Brehm Coalition researcher, Dr. Peter Arvan who is director of the Michigan Comprehensive Diabetes Center at U-M, says this latest development is big news for PWDs. "When the doc says, 'You have type 1 diabetes, so you have no beta cells remaining,' he or she could be wrong. You may have beta cells with little insulin, and further, it might be possible to get insulin back into those empty beta cells."
Arvan says beta cells are highly specialized, and a lot of that specialization comes from turning on some very specific genes and turning off some other very specific genes. "If we know what the turn-on and turn-off switches are, then maybe we can flip those switches, and turn the lights back on. That's the idea," he told us.
What about timing on all this materializing into something concrete for PWDs? Arvan isn't putting a timeline on that.
"Expectations and timelines -- been there and done that," he said. "What you have in this Brehm Coalition is a cadre of really strong scientists pulling hard on a problem and asking questions in new ways. But no promises means that you get no false promises -- and that's a good thing. What have we found so far? The basic observation made in multiple labs within the Brehm Coalition is that under disease conditions, we see that we can find 'The Cells Formerly Known as Beta.' But my, how they've changed! We feel that at least some of these cells can be gotten back -- and that would be a good thing."
Of course, we'd be remiss if we we didn't acknowledge that other collaborations exist and are doing very good work too, such as the Diabetes Research Institute in Florida and all the scientists collaborating through the international Cure Alliance they spearheaded. As our friend and fellow D-blogger Scott Strumello has mentioned before: these collaborations are key, and they're what we need more than waiting on individual researchers to finish studies and publish their work in a peer-reviewed journal before any true progress can be made.
It's great to see that kind of collaborative working happening at the Brehm Center, which has a pretty fascinating history in itself in terms of Dee Brehm's D-story (merged from a couple different history pages about the center and coalition):
Dee was diagnosed at 19 while a freshman at Eastern Michigan University in 1949. The treatment and tools for type 1 were primitive -- in fact, Dee would say, "a little scary." The glass insulin syringes were expensive and sterilized for each use; the needles were thick and sharpened with emery cloth. Dee boiled her urine in a test tube, then treated it with a reagent to determine whether she was spilling sugar. Test strips eventually came along to make that process more convenient, but they did not help to provide real-time blood sugar measurement; moreover, the results were only marginally quantitative, thus a top reading of "four-plus" indicated only that her blood-sugar level had been "high." As Dee recalls, "I never knew exactly how high it really was with a reading of 'four-plus'; it could have been 200 or 500. And even that merely represented the situation many hours before, not right now." More accurate blood sugar measurements could be obtained in a lab, but that test usually required three days and thus was not real time either. Personal blood glucose meters did not become available until 1980. Severe hypoglycemia was a constant worry since Dee is labile, and sudden trips to the hospital were often required for injections of glucose.
The long-range outlook for the disease was grim. When Dee and Bill became engaged in 1951, Dee was under the care of Dr. Jerome Conn, chief of endocrinology at the University of Michigan. (Bill was then a U-M graduate student and also working for U-M as a research associate in operations analysis.) Dr. Conn asked to meet with the couple to ensure that they both realized what it would mean to live with the disease. Dee vividly remembers the four dismal prospects that Dr. Conn related to them:
- Dee's life expectancy would be cut short
- She would suffer severe complications
- She probably would not have children
- She would have the disease for the rest of her life. The good news is that Dee has proven her physician wrong on three counts, and no one would be more please than Dr. Conn himself: She has lived with the disease for 60+ years; she has suffered no complications; and she and Bill have a daughter, a son, and six healthy grandchildren.
So, Dee has proven Dr. Conn wrong on three of his four points. In 1990, Bill and Dee set out on a mission to prove doctor Conn wrong on his fourth and last prediction - that Dee will have this disease all of her life. On November 22, 2004, the University of Michigan Health System announced Bill and Dee's extraordinary gift: $44 million to work toward a cure for type 1 diabetes (!).
We hear from scientists that there are so many unknowns when it comes to diabetes research -- every discovery seems to beget new questions and mysteries -- that those of us living with with this illness can feel pretty disillusioned, like the research will never translate into anything meaningful for our lives. But from my perspective, just knowing the work of centers like Brehm and new lines of research like "Baby Beta Cells" are underway gives me hope... that someday, an answer to the riddle of diabetes may be found.