INS and type 2 diabetes mellitus: As positive controls, we confirmed the genetically proxied GK activation were associated with higher plasma insulin level (beta 1.52 per 1% lower HbA1c, 95% CI 0.65–2.38, P = 0.0006) and lower risk of type 2 diabetes (odds ratio [OR] 0.09 per 1% lower HbA1c, 95% CI 0.05–0.17, P = 2.76 × 10−15; Table 1).