Our study revealed that IGF-1 causally increases the risk of Type 2 Diabetes (T2D), while IGFBP-6, adiponectin and INSR decreases the risk (IGF-1, OR 1.02 [95% CI 1–1.03], p = 0.01; IGFBP-6, OR 0.92 [95% CI 0.87–0.98], p = 0.01; Adiponectin, OR 0.837 [95% CI 0.721–0.970], p = 0.018; INSR, OR 0.910 [95% CI 0.872–0.950], p = 1.52 × 10–5). This evidence concerns the gene INSR and type 2 diabetes mellitus.