Residential Greenness and Subtypes of Gestational Diabetes Mellitus: A Metabolomic Investigation

BACKGROUND: While exposure to greenness has been suggested to benefit health, its associations with the risks of gestational diabetes mellitus (GDM) subtypes and underlying metabolic mechanisms remains unclear. METHODS: Based on 1506 pregnant women from the Shanghai Birth Cohort, this study investigated the associations between residential greenness exposure levels in early- and mid-pregnancy, measured by the normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI), and the risks of GDM subtypes. Non-targeted metabolomics was then combined with the metabolome-wide association studies and the "meet-in-the-middle" approach to explore potential biological pathways. RESULTS: Exposure to residential greenness in early- and mid-pregnancy was associated with a decreased risk of GDM, especially insulin-resistant GDM (GDM-IR). Each IQR increase in greenness exposure indexes was associated with 21 % [OR (95 %CI): 0.79 (0.62, 1.00)] to 25 % [OR (95 %CI): 0.75 (0.57, 0.97)] reduced risk of GDM, as well as 34 % [OR (95 %CI): 0.66 (0.46, 0.94)] to 48 % [OR (95 %CI): 0.52 (0.33, 0.82)] decreased risks of GDM-IR across different periods. Non-targeted metabolomics analysis identified 16 metabolites that were significantly associated with residential greenness, GDM-IR, or total GDM, mainly including fatty acids, lipids, steroids, and hormones. Pathway enrichment analysis identified two significant pathways: α-linolenic acid metabolism and ω-3/ω-6 fatty acid synthesis. CONCLUSIONS: Exposure to residential greenness was associated with lower GDM risks, especially GDM-IR. These observed associations may be partly explained by alterations in the metabolites of sulfatide and androsterone sulfate, as well as α-linolenic acid metabolism and ω-3/ω-6 fatty-acid synthesis.