Bellin, Melena , M.D.
Sitagliptin therapy to improve outcomes after islet autotransplantation
General Research Subject: Type 1 Diabetes
Type of Grant: Clinical Translational Research
Project Start Date: January 1, 2011
Project End Date: December 31, 2013
Diabetes Type: Type 1 diabetes
One emerging therapy to treat diabetes involves transplantation of the insulin producing cells of the pancreas, or islet transplant. Although islet transplant can successfully restore insulin independence in patients with a long history of diabetes, there are shortcomings of this technique. A very large number of islets are required (often from multiple donors), and the body can reject or destroy the donor islets. Medications that protect the islets from dying would be one strategy to improve outcomes.
Some patients need to have their pancreas removed because of severe pain (chronic pancreatitis). These patients can get an islet transplant of their own cells (called islet autotransplant) at the time the pancreas is removed. These patients are ideal candidates to try new medications to protect the islets.
This primary goal of this study is to determine if a medication called sitagliptin can increase the success of islet transplant. This medication increases the level of hormones called GLP-1 and GIP in the blood. GLP-1 and GIP help the beta cell (insulin producing cell of the islet) make more insulin. They may also protect the beta cell from dying or even stimulate development of new beta cells. In this study, patients will get sitagliptin or placebo (sugar pill) for 1 year. The study will analyze whether insulin independence rates are higher in the patients who get active drug than the placebo group.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
This study will investigate whether a diabetes medication, called sitagliptin, can improve the success of islet transplantation (transplant of the insulin producing cells to cure diabetes). It will also indirectly study whether this medication called sitagliptin can protect the beta cells (insulin producing cells) from harm under stressful conditions.
The patients in this study are having their own pancreas removed (because of a painful inflammation of the pancreas) and then the islet cells (insulin producing part of the pancreas) are isolated from the rest of the pancreas and transplanted back into the liver. These patients are very similar to patients with type 1 diabetes who get an islet transplant from a donor, except that these patients do not require medications to keep them from 'rejecting' the transplanted cells. At the time that the pancreas is removed, participants are assigned at random to get the medication sitagliptin or a placebo (sugar pill).
We will study if the islet transplant is more successful in the patients who get the sitagliptin. Sitagliptin increases a person's own body levels of two hormones called GLP-1 and GIP-1. We know in animal models, these hormones are very important in keeping the beta cells healthy, making the beta cells increase in number, and protecting beta cells from death. Our goal is to see if these effects make islet transplant more successful by protecting the transplanted cells.
We hope that this project will help us move closer to a cure for diabetes mellitus, by making replacement of the beta cells more successful.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
We hope that we can achieve two important goals with this study:
1) Make islet transplant more successful by giving a once a day drug that helps the body's own hormones protect the transplanted cells. This will help us move closer to a cure for diabetes (by successfully replacing the insulin producing cells of the pancreas).
2) Better understand if the GLP-1 and GIP-1 hormones are important for maintaining the health of beta cells in people, as they are in animals.
If successful at protecting transplanted islets, the drugs that increase these hormone levels might also be useful in other diabetes settings (like minimizing damage to cells early in diabetes).
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
I do not have diabetes myself, but have been very compelled by those around me who do. Although treatments for diabetes are much better than decades ago, we still do not have a cure, and it requires a lot of effort to take good care of diabetes for every person affected. I believe that we will move to a cure (or cures) in the near future, and that a good method of replacing or regenerating insulin producing cells for patients with long-standing diabetes will be part of this cure.
I hope that we will find a successful therapy that will move us closer to better islet transplant outcomes with this study. The funding from ADA provides the majority of funding for this study, which is larger than almost any clinical trial in islet transplant to date. It will also be a foundation for me in building a career in research in beta cell replacement therapy.
In what direction do you see the future of diabetes research going?
I think that future diabetes research will need to go in multiple directions to address all the facets of this disease. One must find a way to cure long-standing diabetes-which is where I think beta cell replacement therapies will be key-but you also need to find a way to prevent diabetes or stop early onset diabetes, and prevent complications in those with long-standing disease. This is why the field of diabetes research needs to be so large and broad.
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