IRS1 and type 2 diabetes mellitus: First, certain genetic variants exhibit sex-dimorphic effects, with some loci demonstrating larger or more penetrant effects in males—for example, variants at IRS1 show male-specific effects on fasting insulin and the 11p15.5 region, which harbors genes involved in insulin production such as KCNQ1, has been implicated in male-specific T2D risk, potentially influenced by maternal inheritance patterns39–42.