Biomarkers are trace elements in the blood that provide important clues about the body's health. Healthcare and research capabilities around the world are now being upgraded to read and interpret these elements. With the help of biomarkers, for example, one could diagnose diseases caused by dopamine deficiency in the brain, provide better epilepsy diagnostics, and determine which individuals would benefit most from a specific treatment for conditions such as diabetes.
"It is of great significance that we can predict the risk of developing a specific disease with the help of biomarkers, as there may be ways including self-care to prevent the disease from developing – depending on the disease in question. For example, we know that diet and lifestyle choices are important in preventing type 2 diabetes and stroke," says Yang de Marinis, Associate Professor at Lund University.
Yang de Marinis emphasizes that if a blood test can indicate that an individual has a high risk of developing, for example, a stroke in the future, it could provide valuable information to help reduce the risk of occurrence.
Elevated Follistatin levels – a signal to take seriously
A couple of years ago, Yang de Marinis and her research group, along with 22 different partners – research institutes, hospitals, universities, and pharmaceutical industry across Europe, the US and China –discovered that a protein in the blood, Follistatin, can predict type 2 diabetes up to nineteen years before the onset of the disease. This is independent of other known risk factors such as age, BMI, diet, or physical activity. But is there more we can learn through this biomarker?
"With elevated levels of Follistatin in the blood, there is a high proportion of free fatty acids in the bloodstream, which affects various organs in the body. In this new study, we investigated whether there is a connection between the development of other diseases and this marker," explains Yang de Marinis, who led the research.
Using data and biological material from the Malmö Diet and Cancer Cohort study – where participants have been followed for more than 22 years – researchers examined how elevated Follistatin in the blood is linked to illness. The study, published in Nutrition, Metabolism, and Cardiovascular Diseases, shows that elevated Follistatin levels in the blood are associated with early death and several metabolic diseases later in life. Previously, researchers had observed that high levels of Follistatin increase the risk of developing diabetes, and here they showed that this also increased the risk of early death even in individuals without diabetes.
"In addition, we saw that elevated levels of Follistatin were also associated with stroke, ischemic stroke, coronary artery disease, and most strongly with chronic kidney disease –with or without diabetes. For example, the risk of stroke was about 50 percent higher in the group with the highest levels of Follistatin compared to the group with the lowest levels. The risk of developing chronic kidney disease was also twice as high in the group with the highest Follistatin levels. So, elevated Follistatin levels are a signal to take seriously; they are a warning of the risk of several severe diseases and early death," says Yang de Marinis.
She points out that a weakness of the study is that the population studied is only Scandinavian (from the Malmö Diet and Cancer Cohort). Currently, studies are underway on cohorts that include more ethnic groups to investigate how abnormally high levels of Follistatin can be reduced, thereby reducing the risk of diseases.
Blood test that reads and interpret Follistatin
With support from Lund University's innovation department (LU Innovation), Yang de Marinis has developed a blood test that, with AI algorithm, reads and interpret Follistatin levels in the blood, together with other measurements, to efficiently predict diabetes risk.
"The test is called LDcoder, and we are working to launch it in 2024. Our hope is that it can help identify those with elevated Follistatin levels and disease risk, thereby helping individuals prevent diabetes and hopefully other diseases as well," says Yang de Marinis.
Follistatin is related to our metabolism and is regulated by various hormones such as insulin and glucagon. Under normal physiological conditions, insulin inhibits the secretion of Follistatin from the liver, while glucagon stimulates it. If metabolism is dysregulated, for example, due to poor lifestyle habits or obesity, an individual may have an imbalanced regulation leading to high levels of insulin, high Follistatin, and elevated blood lipid levels.