Title: Earlier Life Exposure to Environmental Determinants Over Time and Risk of Type 2 Diabetes Mellitus among Adults: A Systematic Review

Abstract Background This systematic review examined how long-term earlier life exposure to various physical (pollution, built environment) and social (area-level deprivation) environmental determinants (EDs) influences the risk of developing type 2 diabetes mellitus (T2DM) in adulthood using a comprehensive methodology not previously envisaged. Methods The search strategy encompassed six databases (PubMed Central, Embase, Elsevier, CINAHL Plus, Web of Science, EBSCOhost) and grey literature. We screened studies with full-text available and participants aged 18 or older. A risk of bias (RoB) assessment was performed, and a narrative synthesis was produced. Results A total of 169 studies were included as follows: area-level socioeconomic deprivation (18.9%), cultural norms related to land management (LM) (13.6%), food landscape (3%), built environment related to physical activity (PA) (3.6%), chemical pollution (56.8%), noise pollution (2.4%), and light pollution (1.8%). None of the studies were classified as 'low risk', 11 were rated 'high risk', and 158 were rated 'moderate risk’. No consistent evidence linked built environment PA with T2DM, whereas positive longitudinal associations were with food landscape (Adj_ES between 1.03 and 3.12), chemical pollution (Adj_ES between 1.01 and 9.26), light pollution (Adj_ES between 1.01 and 1.30), and noise pollution (Adj_ES between 1 and 1.05). In contrast, negative longitudinal associations were found with area-level socioeconomic deprivation (Adj_ES between 0.62 and 0.99) and cultural norms LM (Adj_ES between 0.97 and 0.99). Rural (Adj_ES between 1.25 and 1.37) and urban (Adj_ES between 1.16 and 1.29) differences, as well as differences between women (Adj_ES between 1.17 and 1.31) and men (Adj_ES between 1.06 and 1.20), were observed for chemical pollution. Meanwhile, sex/gender differences regarding cultural norms LM were inconclusive. Discussion This review corroborated the substantial role of earlier life EDs (excluding built environment PA) in T2DM risk among adults over time, as highlighted in previous reviews. However, caution is advised in interpretation due to biases and issues of generalizability. Research in this field should be encouraged in various income countries and among diverse ethnic populations, using improved cohort study designs before implementing cross-sectional interventions in public health and land management.