Diabetes is on the rise and over time, diabetes can lead to complications such as cardiovascular and kidney disease. An international study led by Lund University shows that follistatin can be used as a biomarker for predicting type 2 diabetes. Follistatin is a protein that is linked to metabolism.
”We discovered that follistatin in the bloodstream can be used as a biomarker for detecting the risk of type 2 diabetes in people who have not yet developed the disease,” says Yang De Marinis, associate professor with a research focus on genetics and diabetic complications at Lund University Diabetes Centre (LUDC), who led the study.
The interdisciplinary study, published in Nature Communications, is a collaboration between several research institutes, hospitals and pharmaceutical companies from Europe, the US and China. The research is based on four populations of around 6500 individuals from different parts of Europe. The association between circulating follistatin and type 2 diabetes risk was first discovered in the Malmö Diet and Cancer study in Sweden. Among the 4195 individuals who participated in the study, 577 developed type 2 diabetes during a 19 year follow-up.
”People who appeared healthy and later developed type 2 diabetes had higher levels of follistatin at the beginning of the study, compared to individuals who did not develop the disease. The association is not affected by other risk factors, such as age, body mass index, diet, smoking history, dietary habits or physical activities,” says Yang De Marinis.
The findings held true when validated and replicated in a Finnish population study with a follow-up period of four years.
Higher insulin resistance
The study also provides a better understanding of how follistatin affects insulin resistance and free fatty acid release in individuals with the risk of developing type 2 diabetes. MRIs (magnetic resonance imaging) showed that individuals with higher levels of follistatin also had a higher insulin resistance in the fat tissue, higher liver fat as well as more free fatty acid in the bloodstream. Experiments in vitro, using human stem cell-induced fat cells, demonstrated that follistatin increases free fatty acid release from the fat cells.
”Our findings suggest that elevated levels of follistatin may lead to fat accumulation in the liver and insulin resistance. This may explain why high levels of follistatin increase the risk of type 2 diabetes,” says Yang De Marinis.
Mapping of genes
To explore the genetics behind high levels of follistatin, the researchers performed genome-wide association studies (GWAS) in two different populations. One gene, GCKR (glucokinase regulatory protein) showed a very strong association to high levels of follistatin, which suggests that the gene is a regulator of follistatin.
”The study demonstrates that follistatin is a new biomarker that predicts the risk for type 2 diabetes several years before diagnosis. We also describe mechanisms that explain how elevated levels of follistatin contributes to the development of type 2 diabetes. In the future, I hope our biomarker can be used to take preventive actions,” says Yang De Marinis.