INS and type 2 diabetes mellitus: Evidence for a negative effect between T2D and BMI was observed for both beta-cell (IVW Beta − 0.04, 95% CI − 0.06: − 0.01, p = 2.06 × 10−02) and insulin resistance pathways (IVW Beta − 0.05, 95% CI − 0.09: − 0.01, p = 1.52 × 10−02), with no evidence of horizontal pleiotropy (Fig. 3D) (Additional file 1: Table S11 and S12).