Context‐Dependent Inverse Association of Glucose–Lipid Metabolic Status With Anemia: Evidence From Multinational Multicohort Analyses

BACKGROUND: The hematological implications of systemic glucose-lipid metabolic status remain poorly understood. We investigated its association with anemia across diverse populations. METHODS: Six analytic cohorts comprising 70,350 unique participants from China, the United States, and the United Kingdom were analyzed using cross-sectional, longitudinal, and extended time-to-event approaches. Dose-response patterns, anemia morphology, effect modification, and an exploratory renal-function-related pathway were evaluated. RESULTS: A higher glucose-lipid metabolic index was consistently associated with lower odds of prevalent and incident anemia, with fully adjusted ORs ranging from 0.53 to 0.87 per 1-unit increase. Extended ELSA follow-up showed a similar association (HR, 0.61; 95% CI, 0.43-0.87). Longitudinal associations were approximately linear, whereas cross-sectional relationships flattened at higher levels. The inverse association was evident for microcytic and normocytic anemia, attenuated with greater systemic inflammation, and stronger among participants with heart disease. An exploratory indirect association through cystatin C accounted for 16.33% of the observed association. CONCLUSIONS: Higher glucose-lipid metabolic status was reproducibly associated with lower anemia occurrence, but this relationship varied across inflammatory, cardiovascular, and renal contexts. These findings suggest that metabolic states conventionally linked to vascular risk may carry distinct implications for hematological homeostasis and metabolic reserve.