Levels of four proteins — IL8, IL-1Ra, MCP-1 and MIP-1-beta — that help protect tissue from attack by the immune system are significantly lower in the blood of patients with type 1 diabetes than those without the disease, new data published in the Journal of Clinical Endocrinology & Metabolism indicate.
In contrast, first-degree relatives of patients with type 1 diabetes who have the same high-risk genes but do not develop the disease had higher levels of these four proteins circulating in their blood, as do healthy individuals without the disease, study researcher Jin-Xiong She, PhD, director of the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia at Georgia Regents University, said in a press release.
“We are providing evidence that clinical trials with any of these four molecules may work, and if we use them in combination, they may work even better,” She said. “One of the major research foci in our group is to identify biomarkers for various diseases, diabetes, cancer and others. We also want to identify new therapeutic strategies or targets through the discovery of biomarkers.”
For the study, the researchers evaluated 13 cytokines and chemokines using blood samples from 697 children with type 1 diabetes and 681 individuals without antibodies to insulin-producing cells. They also examined blood samples from a second set of people, including 1,553 children with type 1 diabetes and 1,493 without any sign of antibodies.
In the first set of samples, the researchers found that levels of IL8 (OR=0.40), IL-1Ra (OR=0.42), MCP-1 (OR=0.60) and MIP-1 (OR=0.63) were significantly lower in patients with type 1 diabetes vs. those without the disease. These findings were confirmed in the second set of samples (IL8, OR=0.43; IL-1Ra, OR=0.56; MCP-1, OR=0.61; and MIP-1, OR=0.69).
Additionally, results showed that significantly more people with type 1 diabetes had protein levels in the bottom quartile vs. the top quartile for IL8 (OR=0.09), IL-1Ra (OR=0.18), MCP-1 (OR=0.38) and MIP-1 (OR=0.44).
Furthermore, the negative associations between type 1 diabetes and levels of all four proteins in the blood appeared to be stronger in the genetically high-risk groups vs. those at moderate to low risk for the disease, according to the data.
“Their pancreatic cells are not secreting enough of these proteins,” study researcher Sharad Purohit, PhD, a biochemist at the Medical College of Georgia at Georgia Regents University, said in a press release. “Normally you are secreting enough of these cytokines so you prevent attack by the immune system.”
People with high levels of these four proteins in their blood who also have three of the known high-risk genes for type 1 diabetes are less likely to have the disease. Purohit noted that this suggests that these proteins may even protect those who have a high genetic risk for type 1 diabetes from developing the disease.
“If the individuals with high-risk genes weren’t making more of the proteins, they likely would have diabetes,” study researcher Ashok Sharma, PhD, a bioinformatics expert at the Medical College of Georgia, said.