Impaired vascular relaxation in type 2 diabetes: A systematic review and meta-analysis.

Type 2 diabetes (T2D) significantly increases the risk of vascular complications (12-32 %), which are a major cause of death (over 50 %) in T2D patients. In T2D, both endothelial (ET) and vascular smooth muscle (VSM) cells are impaired, which act as independent risk factors for cardiovascular disease. Thus, the question of this systematic review and meta-analysis is: Do ET-dependent and -independent VSM relaxation impair in T2D? We systematically searched PubMed and Scopus databases until March 2024; 44 eligible clinical trial studies (68, 16, 30, and 50 study arms for acetylcholine (ACh), methacholine (MTH), sodium nitroprusside (SNP), and glyceryl trinitrate (GTN)) published were included. ET-dependent VSM relaxation in response to ACh (overall ES = -28.9 %, 95 % CI: -35.2, -22.7; p<0.001) and MTH (overall ES = -55.3 %, 95 % CI: -63.6, -47.1; p<0.001) decreased in T2D patients compared to controls. ET-independent VSM relaxation in response to SNP (overall ES = -17.2 %, 95 % CI: -35.2, -22.7; p<0.001) and GTN (overall ES = -63.2 %, 95 % CI: -81.0, -45.5; p<0.001) decreased in T2D patients compared to controls. Our meta-analysis showed reductions in both ET-dependent (~40 %) and ET-independent (~25 %) VSM relaxation. The decrease was more pronounced for MTH (~55 %) compared to ACh (~30 %) and for GTN (~63 %) compared to SNP (~17 %). These findings suggest that dysfunction of both ET and VSM contributes to impaired VSM relaxation in T2D patients. See also the graphical abstract(Fig. 1).