An analysis of proteins circulating in the blood has identified new biomarkers, or indicators, that may improve risk prediction and treatment of type 2 diabetes. The study, led by researchers at Oxford Population Health and Peking University, is published in Diabetes Care.
Proteins that are carried around our bodies in our blood play a key role in keeping us healthy. The levels of some types of proteins in our blood can tell us how likely or unlikely we are to develop some health conditions.
Advances in techniques to measure proteins in our blood mean that researchers can now quantify the levels of several thousand proteins in very small quantities of blood samples. Analysing these proteins alongside genetic markers in people who have a disease, such as type 2 diabetes, and then comparing the results with people who do not have the disease, can uncover proteins that may be responsible for causing diseases. This improves our ability to predict who may be at risk of developing disease and may lead to the development of new treatments.
The study used data from participants in the China Kadoorie Biobank (CKB), a long-term collaborative study between Oxford Population Health and Peking University, which recruited over 500,000 healthy adults from 10 diverse areas in China during 2004 and 2008. In this study, researchers measured levels of 2,923 proteins in the stored blood samples from 2,026 randomly selected participants who did not have diabetes by the time their blood samples were analysed, and 92 individuals who developed type 2 diabetes during 11 years of follow-up.
The researchers then carefully analysed the data using a range of conventional and genetic methods, including use of genetic variants that affect the levels of specific proteins in the blood.The researchers also wanted to understand whether or not their findings could be applied to non-Chinese populations so they replicated the study with data on a European population from the UK Biobank.
Key findings:
- Overall 33 proteins were significantly associated with risk of type 2 diabetes in the CKB participants; these were all replicated in further analysis of data from European populations for type 2 diabetes;
- Analysing the presence of these 33 proteins in blood samples in addition to considering conventional risk factors substantially improved the ability to predict the risk of type 2 diabetes in CKB, with comparable performance in European populations;
- Of the 33 proteins, genetic analysis provided evidence that three proteins (ENTR1, LPL and PON3) may be responsible for causing type 2 diabetes in the CKB participants. This evidence was replicated for one protein (LPL) in Europeans using different genetic variants;
- Except for LPL, no previous genetic studies have been able to confirm the causal role of ENTR1 or PON3 in the development of diabetes;
- A range of additional follow-up analyses provide further support for two proteins (PON3 and ENTR1) being potential new treatment targets and one protein (LPL) being a repurposing target (using existing medicines for new purposes) for type 2 diabetes.
Dr Pang Yao, Molecular Epidemiologist at Oxford Population Health and lead author of the study, said ‘Our findings demonstrate the value of integrating proteomic* and genomics* data, even at moderate scale, in biobank studies to improve risk prediction and discover novel drug targets for type 2 diabetes.’
Professor Liming Li, a senior author and CKB China Principal Investigator from Peking University, said ‘Most drugs targets are proteins and large biobank studies such as CKB provide a unique opportunity for undertaking cutting-edge discovery research related to drug development.’
Professor Zhengming Chen, a senior author and CKB UK Principal Investigator said ‘The results highlight the importance of proteomics for risk prediction and discovery of novel treatment targets for type 2 diabetes. By providing supporting evidence that these proteins may cause type 2 diabetes, we offer new avenues for therapeutic interventions that could have significant implications for development of precision health.’
*Proteomic studies analyse large number of proteins that are produced by each cell in our bodies and how these proteins work. Many of the proteins can be detected in the blood.
*Genomics is the study of all the DNA in our bodies, including genes that are responsible for telling our cells how to produce proteins that are analysed in proteomic studies.