Modifiable risk factors and plasma proteomics in relation to complications of type 2 diabetes.

A comprehensive assessment of combined modifiable risk factors with common complications of type 2 diabetes (T2D) is lacking, and the potential role of proteomics remains unclear. Here, we examine the associations of cardiovascular health (CVH) score and degree of risk factor control with common diabetic complications using data from the UK Biobank (n = 14,102). Furthermore, we explore the mediation effects of plasma proteomics in a subset with proteomic data (n = 1287). Over median follow-ups of 12.4-13.4 years, higher CVH score and higher degree of risk factor control are associated with lower risks of 30 and 22 of 45 adverse outcomes among individuals with T2D, respectively. Mediation analyses reveal that mortality and multiple vascular diseases share common mediators, such as uromodulin and pro-adrenomedullin. These findings highlight the importance of risk factors modification in reducing disease burden among people with T2D and facilitate the understanding of mediation effects of plasma proteins underlying these associations.