October 10, 2017 (Miami, FL) — People with type 1 diabetes are typically diagnosed once they begin displaying the usual signs and symptoms of the disease. In most cases, this is long after the majority of insulin-producing cells in the pancreas have been irreversibly destroyed, requiring patients to take life-long insulin therapy to normalize blood sugar levels. If scientists could detect diabetes earlier or possibly predict who is likely to develop it in the near future, it may open the door to developing new therapies or start interventions earlier when they can be more effective at preventing the further destruction of the beta cells.
Now, findings from a recent Diabetes Research Institute study are the first steps toward establishing a unique “metabolic signature” that may serve as an early biomarker of diabetes development. The study, published in the Journal of Proteome Research, was the first longitudinal analysis of the significant biochemical changes that occur at the onset of the disease and throughout its progression.
Using highly advanced mass spectrometry-based analytical technology, Peter Buchwald, Ph.D., director of drug discovery at the DRI, and his team studied the effect that diabetes has on the overall biochemical composition in a widely used mouse model of type 1 diabetes, which closely mimics the disease process in patients. They were able to detect and quantify more than 700 metabolites – small-molecule chemical compounds that are present in the body – in blood and other samples collected over time and discovered that many of them have significantly different concentrations in those that progress to diabetes. (Pictured: Dr. Peter Buchwald, DRI Director Dr. Camillo Ricordi, Marta Garcia-Contreras, and Alejandro Tamayo-Garcia.)
“We were trying to accomplish two things through this study. First, to identify some metabolites that change very early on and that might serve as biomarkers of diabetes onset. Second, to map out all of the changes that occur in the metabolic picture over time as the individuals become diabetic. We found that a large percentage of the compounds, more than 50 percent, change significantly in those who become diabetic, some change very significantly –- up to four or five-fold compared to the controls, and a few change even more than 10-fold,” explained Dr. Buchwald. “So we now have a nice, full picture of everything that changes as diabetes develops and progresses over time.”
The findings also raise the possibility of identifying biomarkers that can serve as an early predictor of type 1 diabetes onset. In a series of next steps, the researchers will be working to translate these results to people living with T1D.
“We have identified several possible early biomarkers in these experimental models so certainly we’re going to look much closer at them in patients, try to collect samples and study those metabolites that are of interest. We are also thinking about using such so-called metabolomics studies that look at the chemical fingerprints of cellular processes not just to identify biomarkers and metabolic signatures of diabetes, but also to identify the effectiveness of therapeutic interventions and develop individually customized precision medicine-type interventions,” said Dr. Buchwald.
Illustration of metabolic pathways that showed large change in diabetic animals (circle graphs) and of some compounds that showed large change in diabetic animals (line graphs).
About the Diabetes Research Institute
The Diabetes Research Institute at the University of Miami Miller School of Medicine leads the world in cure-focused research. As the largest and most comprehensive research center dedicated to curing diabetes, the DRI is aggressively working to develop a biological cure by restoring natural insulin production and normalizing blood sugar levels without imposing other risks. Researchers have already shown that transplanted islet cells allow patients to live without the need for insulin therapy. Some study participants have maintained insulin independence for more than 10 years. The DRI is now building upon these promising outcomes by developing a DRI BioHub, a bioengineered “mini organ” that mimics the native pancreas. While various BioHub platforms are being tested in preclinical and clinical studies, the DRI is also developing strategies to eliminate the need for anti-rejection drugs and reset the immune system to block autoimmunity. For more information, please visit DiabetesResearch.org, call 800-321-3437, or Tweet @Diabetes_DRI.
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Lori Weintraub, APR