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DRI Study Points to Potential New Type 1 Diabetes Biomarker

(September 2017) - A “biomarker” is a medical sign—or indicator—that a biological state or condition exists. Biomarkers are used in all facets of medical research to test for the presence of a disease and/or the effectiveness of therapies to treat it.

In type 1 diabetes, the presence of circulating autoantibodies that attack the insulin-producing beta cells have been the only biomarkers clinically available, to date, to identify potentially at-risk patients. [1] Researchers at the Diabetes Research Institute (DRI) may have identified a new type 1 biomarker: the miRNA-enriched exosome.

ExosomesExosomes are tiny bubbles, or vesicles, that are released from practically every cell in the body and contain genetic information specific to that cell. Once thought of as vesicles that only carried waste, exosomes have recently been implicated in cell-to-cell communication and in the transmission of some diseases. They are also being explored as a means of drug discovery.[2]

In the world of type 1 diabetes, exosomes can release different types of information about the insulin-producing cells found within the islets of the pancreas, the beta cells.

“These microscopic vesicles in the blood that are released by certain types of cells in the body can carry a specific signature that can tell a story,” says DRI Director Camillo Ricordi, M.D. “Exosomes and other microvesicles can be considered 'liquid biopsies' because they greatly concentrate signals that could be undetectable in the whole blood.”

Armando Mendez, Ph.D., director of the DRI's Clinical Chemistry Lab, says that back in the 1980s, he used to think of exosomes as being "small parts of the cells' membrane that would shed off as part of normal membrane recycling,” and of little biological importance. 

Mendez admits that that way of thinking has evolved and changed over the years.  

Study Finds Exosome miRNA to be a Diagnostic Signature for Type 1

According to a recent DRI study that was published in Nature’s Scientific Reports, exosome microRNA (miRNA) was evaluated as a possible predictive biomarker for T1D.

Certain small molecules of RNA called microRNAs (miRNA) have been shown to be specific to and plentiful in healthy islets, making them potential candidates for biomarkers of beta-cell loss. [3] DRI researchers say that miRNA present in exosomes could make for ideal biomarker candidates because not only are they seemingly tissue specific (like for islets), but they are also stable in the blood and could thus, be used as a ‘test’ or indicator once established.

Some miRNA found to be ‘differentially expressed’ in people with type 1

For the study, lead author and senior research associate Marta Garcia-Contreras, began by specifically looking for differences in miRNA in people with type 1 diabetes.

The researchers obtained human blood samples from 24 people with T1D and 24 control subjects, and isolated exosomes from the plasma of these blood samples.

Garcia-Contreras and DRI investigators found seven different miRNAs that were “differentially expressed” in people with type 1 diabetes.

“Some of the miRNAs that we found—not all of them, but some—have been found in other studies in type 1,” she says. “For example, [the miRNA] miR25-3p, was up-regulated in our samples and it is a miRNA that has been found in new-onset type 1 patients, and has been implicated in glycemic control.”

Another miRNA, which DRI investigators found to be “down-regulated” was miR378e, which targets insulin-like growth factor receptors and is also involved in lipid metabolism.

The results of the study show that the DRI researchers have been able to identify several circulating miRNAs that are deregulated in plasma-derived exosomes from individuals with type 1 diabetes compared with control subjects.

Does knowing this mean we can possibly screen for type 1 diabetes in the future?

Garcia-Contreras points out that participants in the study were all people who had had type 1 diabetes for a long period of time, and that potentially these “up-and-down-regulated” miRNAs would be deregulated similarly in people with newly diagnosed type 1, as well.

Knowing what the researchers now know, the question was asked as to whether it might be possible—in the future—to screen for these deregulated miRNAs in people that might be considered at risk for type 1 diabetes.

“What would be relevant would be to repeat the same study with patients that have been recently diagnosed,” say Garcia-Contreras. 

Garcia-Contreras adds that if somebody is genetically susceptible to developing type 1 diabetes, the DRI could possibly one day screen the patient for these particular biomarkers and perhaps intervene before type 1 diabetes develops.

This is the first paper in type 1 diabetes using these types of miRNAs and exosomes in the blood of those with type 1 diabetes. According to Dr. Ricordi, “The study provides suggestive evidence for the role of exosome miRNAs as clinically applicable biomarkers in T1DM. Exosomes are becoming central not only for diagnosis of a specific disease state, but could also serve as indicators of tissue damage/destruction, like in the case of transplant rejection.  They could be useful to monitor disease progression, or the benefit of a specific therapeutic intervention. Finally, exosomes could also be used as therapeutic agents that could deliver therapeutic signals selectively to specific tissues or cells.  These are all reasons why we are so excited about this emerging area of biomedical research.”

[1] http://care.diabetesjournals.org/content/38/6/989

[2] https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0268-z

[3] https://www.ncbi.nlm.nih.gov/pubmed/24666639?dopt=Abstract


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By Daniel Trecroci

 


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