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Dietary manganese, plasma markers of inflammation, and the development of type 2 diabetes in postmenopausal women: findings from the Women’s Health Initiative

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posted on 15.04.2020 by Jung Ho Gong, Kenneth Lo, Qing Liu, Jie Li, Shuiqing Lai, Aladdin H. Shadyab, Chrisa Arcan, Linda Snetselaar, Simin Liu
Objective: To examine the association between manganese intake and the risk of type 2 diabetes in postmenopausal women and determine whether this association is mediated by circulating markers of inflammation.

Research Design and Methods: We included 84,285 postmenopausal women without history of diabetes from the national Women’s Health Initiative Observational Study (WHI-OS). Replication analysis was then conducted among 62,338 women participated in the WHI-Clinical Trial (WHI-CT). Additionally, data from a case-control study of 3,749 women nested in the WHI-OS with information on biomarkers of inflammation and endothelial dysfunction were examined using mediation analysis to determine the relative contributions of these known biomarkers by which manganese affect T2D risk.

Results: Compared with the lowest quintile of energy-adjusted dietary manganese, WHI-OS participants in the highest quintile had a 30% lower risk of type 2 diabetes (hazards ratio [HR] 0.70 [95% CI 0.65, 0.76]). A consistent association was also confirmed in the WHI-CT (HR 0.79 [95% CI 0.73, 0.85]). In the nested case-control study, higher energy-adjusted dietary manganese was associated with lower circulating levels of inflammatory biomarkers that significantly mediated the association between dietary manganese and type 2 diabetes risk. Specifically, 19% and 12% of type 2 diabetes risk due to manganese were mediated through interleukin 6 and high-sensitivity C-reactive protein, respectively.

Conclusions: Higher intake of manganese was directly associated with a lower type 2 diabetes risk independent of known risk factors. This association may be partially mediated by inflammatory biomarkers.

Funding

The WHI program is funded by the NHLBI, NIH, US Department of Health 330 and Human Services, through contractsHHSN268201600018C, 331 HHSN268201600001C, HHSN2682-01600002C, HHSN268201600003C, and 332 HHSN268201600-004C.

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