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Sex-specific associations of insulin resistance with chronic kidney disease and kidney function: a bi-directional Mendelian randomisation study – published online 15/05/2020

Jie V. Zhao, C. Mary Schooling

Chronic kidney disease (CKD) contributes substantially to the global burden of morbidity and mortality. Notably, CKD has a sexual disparity that is not fully understood. To provide further insight, in this issue Zhao and Schooling (https://doi.org/10.1007/s00125-020-05163-y) contextualise these differences within evolutionary biology theory, which suggests a sex-specific growth and reproduction trade-off against longevity. As such, insulin, a key driver of this trade-off, may have different roles in men and women. Given fasting insulin, fasting glucose and HbA1c are related, the authors used the novel Mendelian randomisation-Bayesian model-averaging (MR-BMA) method to identify the best-fitting model and most influential exposure, followed by univariable or multivariable Mendelian randomisation, as appropriate. Fasting insulin was selected as the most likely exposure by both overall and sex-specific MR-BMA. Genetically predicted insulin was associated with CKD and unfavourable kidney function in men but not women. The authors suggest that clarifying the underlying pathways by which insulin has these sex-specific renal effects could provide new insights for prevention and treatment strategies for CKD.

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