Although the role of manganese (Mn) in the development of diabetes has been a concern, epidemiological studies directly linking Mn exposures to glucose homeostasis in a sex-dependent context are rare. We evaluated the associations of Mn levels in both blood and urine with glucose levels, insulin resistance, and kidney function among general populations and potential heterogeneities by sex. We performed a cross-sectional analysis of population-based data in the National Health and Nutrition Examination Survey (NHANES) involving 1417 adults in 2011-2016. We estimated the associations between blood and urinary Mn levels with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), insulin, and estimated glomerular filtration rate (eGFR) by using categorical and spline analyses. There were significant positive linear relationships between urinary Mn with FPG (P<overall=0.003, P<nonlinear=0.817) and HbA1c (P<overall=0.023, P<nonlinear=0.854) among women, while blood Mn levels were associated HOMA-IR (P<nonlinear=0.042) and insulin (P<nonlinear=0.014) with J-shaped dose-responses among men. For eGFR, positive linear relationships were observed with blood Mn in women (P<overall=0.032, P<nonlinear=0.549), and with urinary Mn in both men (P<nonlinear=0.058) and women (P<nonlinear=0.892). In sensitivity analysis, after excluding participants with diabetes, we still observed sex differences in the association between urinary Mn levels with FPG, HbA1c, insulin, HOMA-IR and eGFR.

In summary, blood and urinary Mn levels were independently associated with glucose-related biomarkers with potential heterogeneities by sex. The findings emphasize the probable role of Mn for the glucose-related biomarkers and kidney function, and call for more studies on the risk of diabetes in a sex-specific manner.


J. Yang: None. A. Yang: None. N. Cheng: None. Y. Bai: None.

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