In the reverse direction, genetically predicted peak insulin response was suggestively associated with elevated isoleucine catabolite, 2-hydroxy-3-methylvalerate (β [95% CI] = 0.074 [0.018, 0.130], p <sub>IVW</sub> = 9.20 × 10<sup>-3</sup>).<h4>Conclusions</h4>Our genetic analysis indicates BCAA catabolism and insulin secretion/action interact with each other; their aberrance might form a vicious cycle promoting T2D progression. Here, INS is linked to type 2 diabetes mellitus.