Background The timing of exposure to diet across the lifespan may be critical in the development of T2D. However, no previous study has deciphered the influence of dietary insulinemic and inflammatory potential on the risk of T2D across the lifespan from a life course perspective. Objective This study aimed to evaluate the associations of dietary insulinemic and inflammatory potential with the risk of T2D from a life course perspective. Design This was a prospective cohort study. Participants and setting Data from 40,135 eligible, female participants in the Nurses’ Health Study II were analyzed. Adulthood diet was assessed quadrennially since 1991 using 131-item food frequency questionnaires (FFQ), and adolescent diet was recalled in 1997 using a 124-item high-school FFQ. The main exposures were empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores across different life stages (adolescence, premenopausal adulthood, postmenopausal adulthood) and changes and cumulatively over the lifetime. Main outcome measures The main outcome was incident T2D. Statistical analyses performed Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results Higher EDIH and EDIP scores (highest vs lowest quintiles) were associated with increased lifetime risk of T2D as a lifetime average (HR, 95%CI: 2.72, 2.38-3.11 and 2.04, 1.81-2.30), during premenopausal adulthood (3.18, 2.52-4.01 and 2.31, 1.88-2.82), and postmenopausal adulthood (2.67, 2.15-3.33 and 1.70, 1.41-2.05), but not during adolescence (1.07, 0.95-1.20 and 1.10, 0.98-1.24). The HR, 95%CI associated with higher lifetime averages for both EDIH and EDIP (vs. low lifetime averages for both, based on tertiles) was 2.64 (2.32-3.01). Individuals with high adulthood EDIH or EDIP had similar magnitudes of lifetime risk elevation, regardless of their adolescent EDIH and EDIP status. Adolescent EDIH and EDIP were associated with a slightly increased premenopausal T2D risk (1.24, 1.02-1.51, and 1.24, 1.02-1.50). In additional analyses estimating the time window during which adulthood dietary insulinemic and inflammatory potential influences T2D risk, higher adulthood EDIH or EDIP was associated with an increased risk of T2D with a very short time lag. Conclusions Over the life course in women, high dietary insulinemic and inflammatory potential in both premenopausal and postmenopausal adulthood were independently associated with a substantially increased lifetime risk of T2D. Adulthood offers the most critical time window for dietary interventions to reduce lifetime T2D risk, though adolescent diet may influence the risk of premenopausal T2D.
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