Finally, the adjusted multinomial analysis suggested that higher levels of Ism1 may play a protective role against pre-diabetes (AOR = 0.88, 95% CI = 0.838, 0.925) and T2D (AOR = 0.87, 95% CI = 0.814, 0.934); Conclusions: This study suggests that reduced Ism1 levels are linked to increased insulin resistance, MAFLD, and T2D in obese individuals. This evidence concerns the gene ISM1 and diabetes mellitus.