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Diagnostics Hematology, Genetics and epigenetics, Omics

Diabetes Detector

Diagnosing type 1 diabetes is problematic. Patients only seek out help once symptoms start to arise, but the early stages of the autoimmune disease have already been at work for a number of years. Up until now, there has been no reliable method of detecting early stage, presymptomatic diabetes; however, a recent discovery could be set to change all of that. Scientists at the Medical Research Council’s Clinical Science Centre (CSC) in London, in collaboration with scientists at the Swiss Federal Institute of Technology, have identified microRNAs (miRNAs) that could act as effective biomarkers years before symptoms even develop, as they circulate in the blood during the early stages if the disease (1).

The islets of Langerhans in a patient with type 1 diabetes after receiving treatment to transform α-cells into new β-cells (shown in green). Image courtesy of Monica Courtney, University of Nice-Sophia Antipolis, France.

Specifically, the research team honed in on one miRNA – miR-375. No stranger to being used as a biomarker (having previously been cited (2) as a potential indicator of prostate cancer), studies have revealed miR-375 to be the most abundant among the many miRNAs found within β-cells (3). In fact, mice unable to produce the molecular messenger have shown a decrease in β-cell mass and subsequently develop diabetes, suggesting a crucial role for miR-375 in blood sugar regulation (3). It was this research that inspired Mathieu Latreille, lead of CSC’s Cellular Identity and Metabolism research group, to delve deeper. He explains, “Interestingly, some miRNA molecules have been shown to circulate in body fluids such as the blood, saliva, breast milk and other secretions and have recently become novel markers for several diseases. These findings motivated us to determine if miR-375 could be used as a marker to diagnose the destruction of β-cells that underlies the development of diabetes.”

By analyzing the plasma of β-cell rescue mouse models, Latreille and his team found that a small but significant proportion of circulating miRNA is derived from pancreatic β-cells; his team is the first to demonstrate that β-cells release miR-375 into blood circulation. With these results under his belt, Latreille hypothesized that when these cells become targets of the immune system, the molecular messenger is released into the bloodstream at high quantities as the cells die.

Different models of β-cell stress were created by Latreille to test this hypothesis, who used chemical agents and genetic mutations to damage the insulin-producing cells. One such experiment involved treating mice with streptozotocin (STZ), a molecule which specifically kills β-cells. Three days after STZ injection, the team observed the expected rise in blood glucose as a result of β-cell destruction, but also measured a two-fold increase in miR-375 when compared with controls. Latreille explains that considering the contribution of β-cells to miR-375 levels in the blood is small, he believes that the most likely explanation for this observation is that hyperglycemia per se elicits increased miR-375 secretion from tissues other than pancreatic β-cells. This result encouraged the team to conduct further studies in humans, which complimented these findings when type 1 diabetes patients also showed elevated levels of miR-375.

Whilst the study showed no significant changes in miRNA circulation in type 2 diabetes patients, Latreille believes that in the future, a simple blood test could use miR-375 as an indicator of acute β-cell destruction and autoimmune diabetes. “If we can identify and treat patients earlier, we may be able to help them to avoid secondary complications. This could ultimately extend a patient’s life,” says Latreille. The team now intends to determine whether miR-375 could predict, with greater efficiency than current tests, if an individual is developing type 1 diabetes, years before symptoms arise, and if the miRNA could be effectively used as a surrogate biomarker for the disease.

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  1. M Latreille, et al., “miR-376 gene dosage in pancreatic β-cells: implications for regulation of β-cells mass and biomarker development”, J Mol Med, [Epub ahead of print] (2015). PMID: 26013143.
  2. A Sita-Lumsden, et al., “Circulating microRNAs as potential new biomarkers for prostate cancer”, Br J Cancer, 108, 1925–1930, (2013). PMID: 23632485.
  3. M Stoffel, et al., “miR-375 maintains normal pancreatic alpha- and beta-cell mass”, Proc Natl Acad Sci USA, 106, 5813–5818, (2013). PMID: 19289822.
About the Author
Mathieu Latreille

Mathieu Latreille is part of the Cellular Identity and Metabolism Group, Faculty of Medicine, Imperial College London, UK.

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