Background: Literature on omega-3s and T2D risk has been heterogenous; however, most prior studies have used self-reported dietary intake or short-term supplementation regimens. Thus, further investigation is needed to assess longitudinal associations of circulating omega-3 with early T2D risk phenotypes. Objective: Assess longitudinal associations of circulating omega-3s with changes in insulin sensitivity (IS) and β-cell function (BCF) in the PROMISE cohort. Methods: Adults at-risk for T2D underwent four assessments over 9 years (n=472); blood samples were collected to determine insulin and glucose concentrations, and an OGTT was conducted. Baseline serum omega-3s (ALA, EPA, DPAn-3, DHA) were measured using gas chromatography-flame ionization detection. OGTT values were used to calculate validated IS (HOMA2-%S, ISI) and BCF (IGI/IR, ISSI-2) indices. Generalized estimating equations (GEE) analysis assessed the association between baseline omega-3s (mol%) with longitudinal change in IS and BCF indices after covariate adjustment. Results: Significant positive correlations were shown between EPA and DHA with IS measures (HOMA2-%S: EPA, r=0.18, DHA, r=0.23, all p<0.001; ISI: EPA, r=0.15, p<0.01, DHA, r=0.19, p<0.001) and between DHA and BCF indices (IGI/IR, r=0.14, p<0.01; ISSI-2, r=0.1, p<0.05). In adjusted GEE models, baseline EPA and DHA were positively associated with longitudinal change in IS (HOMA2-%S, p<0.001; ISI , p<0.01), and BCF (IGI/IR, p<0.05) ( Figure ) . Conclusions: Circulating omega-3s (specifically EPA and DHA) were positively associated with IS and BCF, which are important early T2D risk phenotypes. These findings add to growing evidence of the potential role omega-3s have in T2D primary prevention.
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