Diab Vasc Dis Res. 2026 Jul-Aug;23(4):14791641261474108. doi: 10.1177/14791641261474108. Epub 2026 Jul 30.
ABSTRACT
PurposeTo investigate the longitudinal association between domestic water hardness and incident diabetic retinopathy (DR) in individuals with type 2 diabetes (T2D) and identify circulating proteomic mediators.MethodsThis study analysed data from 13,194 participants with prevalent T2D. Domestic water hardness was determined according to residential postcodes. Weighted Cox proportional hazards models and mediation analyses were employed to evaluate associations between water hardness, proteins, and DR risk.ResultsDuring a median follow-up of 13.28 years, 1,505 cases of incident DR were documented. Compared with soft water (<60 mg/L), very hard water (>180 mg/L) was associated with a 49% higher risk of DR (HR, 1.49; 95% CI, 1.12-2.00). The plasma protein GID8 (Glucose-induced degradation protein 8) was identified as a mediator, explaining 6.2% (95% CI, 1.2%-25.5%) of the association.ConclusionThese findings provide some preliminary proteomic insights that domestic hard water may be a novel, modifiable environmental risk factor for DR, potentially mediated through GID8-related pathways. Future research should include mechanistic studies to confirm the biological pathways linking domestic water hardness to diabetic retinopathy.
PMID:42531479 | DOI:10.1177/14791641261474108