The discordance between elevated systemic levels and known tissue-specific reductions suggests that peripheral HIF-1α may reflect a compensatory response to hypoxia rather than a primary driver of T2DM pathogenesis.<h4>Systematic review registration</h4>https://www.crd.york.ac.uk/PROSPERO/view/CRD420251118501, CRD420251118501. The gene discussed is HIF1A; the disease is type 2 diabetes mellitus.