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50-year Survivors Point to Potential Diabetes Cure

Patients with long-term diabetes have both functioning beta cells and C-peptides which seem to offer protection against the disease's debilitating comorbidities. This discovery already has researchers thinking about a way to restore pancreas functionality.

A subset of patients with type 1 diabetes are able to live upwards of half a century without suffering from nephropathy, retinopathy, vascular disease, and other debilitating effects associated with diabetes.

Joslin Diabetes Center has dubbed these patients the Joslin 50-year Medalists, and in studying this unique population for the first time, has discovered that not only did the pancreas of every patient “display active insulin-producing beta cells,” there was evidence of beta cell apoptosis, proliferation, and insulitis.

To George King, MD, Director of Research and Head of the Section on Vascular Cell Biology at Joslin, and senior author of the study, this opens the pathway to a new therapy that could lead to the restoration of pancreas functionality by suppressing autoimmune response and inducing beta cell proliferation through a growth factor.

Further, Dr. King believes that these findings will have implications for the wider type 1 population because of the presence of endogenous C-peptide in both young diabetics and Joslin 50-year Medalists.

MDNG asked Dr. King to discuss the study and its implications in greater depth with us, and he happily obliged. Here’s what he had to say:

You and your colleagues uncovered “signs of cell proliferation, cell death and autoimmune attack” — what does this tell you?

I think the question that’s been raised is that after the long-term diabetes—and these individuals clearly have had diabetes for a very long time—are there residual beta cells still functioning, and if they are there, why? Either they’ve been there forever or they’ve been replenishing themselves. So our study has shown that almost all of these patients have evidence of beta cell survival because we can see beta cells there in the pancreas and we can test the presence of C-peptides.

The second question is, if you do see beta cells there, are they just in there sort of hanging around for 50 years, or are they still growing and proliferating? What we have found, which is exciting, is that we have some evidence of those beta cells proliferating and dying. That actually makes sense because they’ve probably reached some sort of steady-state level in this process. The reason this is important is if we are looking for a treatment, then one possibility is to decrease the destruction and increase the proliferation.

How do you think you’ll approach this treatment that you mentioned?

In most of these cases there’s evidence that, clinically, the patients obviously have type 1 disease. We might have to decrease the immune-mediated destruction of the beta cells. If that occurs, for some of these patients, their pancreas could potentially revive on its own, because two of the pancreases [that we tested] had a large amount of beta cells. So it is not implausible that if you just stop the destructive process, the rest of the beta cells could pick up and proliferate and regenerate.

For those who only have a small number of beta cells left, there may not be enough residual to completely recover. Then we would need some sort of growth factor or some treatment that could induce them to proliferate, either from the differentiated cells or from the stem cells that are present in the pancreas. I don’t know how to do that, so we and others are going to look at it seriously in the near future.

Do you think these 50-year Medalists belong to some sort of diabetes sub-group?

We are only talking about 1,000-2,000 type 1 diabetics who have survived this long. There is probably a special set of people because there are so few of them, but we believe [this potential therapy will be] applicable to the other populations general population as well because in larger studies of younger groups of type 1 diabetics, such as DCCT [Diabetes Control and Complications Trial], we see 20-30% of patients have C-peptides; that’s not as high as [in the Medalist population] which is 60-70% of patients, but I can’t say whether somebody is the same.

One interesting aspect is that even though 60-70% of our patients have C-peptides, when we looked at the pancreases, 100% have positive beta cells. That suggests to me that a large number of type 1 diabetic patients with long-term diabetes, 10, 20, 30 years, will have significant residual beta cells left.

Will you be partnering with anyone as you pursue this research?

This is was done with a fairly small number of pancreases, so hopefully we’ll continue to measure our findings and see that they are consistent with a larger number of patients, as well with more pancreases. We’ll continue collaborating with the Juvenile Diabetes Research Foundation, who has been supporting this, as well as other funding agencies such as NIH. Once we are on firm ground, we hope to collaborate with beta cell groups as well as immunologists to look at ways through which we can regenerate beta cells and decrease immune problems.

Does the idea of pancreas regeneration represent a new “holy grail” of diabetes research like the artificial pancreas?

I think all of these things are important. Ours is one path and we don’t know which one is going to be the best. None of these treatments are probably going to be applicable to everyone. Some patients will probably tolerate an artificial pancreas, but I think if we could regenerate beta cells in their own environment in the pancreas, in the islets, to me that is probably going to be better than an artificial pancreas. When you’re talking about the artificial pancreas, we’re really only replacing insulin, possibly glucagon, but the islet has multiple hormones—some of which we know, some we don’t, somatostatin and others—so to mimic that whole environment, of beta cells and the islet, will be a long time to come.