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

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.

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.

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.

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.