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Sex Differences in the Cardiovascular Significance of Albuminuria in Type 2 Diabetes: A Narrative Review
Carlos Enrique Martínez-Alberto1,2,3, Zuelika Bobadilla-Hernández4, Javier Donate-Correa2,4,5,6,7
1Escuela de Enfermería Nuestra Señora de Candelaria, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain.
Abstract:
Albuminuria is routinely used to assess kidney damage in diabetes, but it also conveys cardiovascular risk across the urinary albumin-to-creatinine ratio (UACR) distribution, including within A1. Whether sex modifies this relationship remains uncertain. This narrative review prioritizes longitudinal studies in type 2 diabetes mellitus (T2DM), analyses within A1 particularly, and distinguishes this direct evidence from the general population or chronic kidney disease cohorts, surrogate-endpoint studies, and experimental mechanisms. A few studies report formal sex-by-UACR interactions for selected outcomes, including mortality in broad kidney-disease populations and heart failure in diabetes. Many other apparent differences derive only from sex-stratified analyses and therefore do not establish effect modification. Differences in urinary creatinine excretion, body composition, hormonal exposure, kidney injury pathways, cardiovascular phenotype, and health-care ascertainment may alter the observed association, but most mechanistic evidence is indirect. Current evidence supports UACR as a continuous prognostic marker in both sexes but does not justify sex-specific diagnostic cut-offs, therapeutic thresholds, or response targets. UACR should be measured systematically, confirmed when abnormal or borderline, preferably repeated under standardized conditions, and interpreted with eGFR and the overall cardiovascular risk profile. Sex may provide additional clinical context; treatment should continue to follow guideline-based indications.
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