Proteomic signatures of type 2 diabetes predict the incidence of coronary heart disease.

Abstract

Emerging evidence reveals a complex association between type 2 diabetes (T2D) and coronary heart disease (CHD), which share common risk factors and biological pathways. This study aims to identify the shared proteomic signatures of T2D and CHD, as well as whether the shared proteins predict incident CHD in T2D patients, and to develop predictive models. Utilizing data from 53,014 UK Biobank participants and 2923 plasma proteins, we identified 488 proteins associated with T2D, of which 125 proteins were also associated with CHD. Among the shared proteins, we determine nine proteins showing causal associations with CHD, including PCSK9, NRP1, and CD27. Mediation analyses suggest that the nine proteins mediate the association between T2D and CHD. By integrating these proteins into our predictive model, we achieved a desirable prediction (AUC = 0.819) for future CHD onset in T2D patients. Additionally, druggability evaluation show 32 potential therapeutic agents, including established antihypertensives and nine novel compounds, suggesting avenues for dual-targeted treatment strategies. Collectively, our findings unveil the proteomic signatures associated with both T2D and CHD, providing implications for screening and predicting future CHD onset in T2D patients.