Löfvenborg, Josefin ECarlsson, SofiaAndersson, TomasHampe, Christiane SKoulman, AlbertChirlaque Lopez, María DoloresJakszyn, PaulaKatzke, Verena AKühn, TilmanKyrø, CecilieMasala, GiovannaNilsson, Peter MOvervad, KimPanico, SalvatoreSanchez-Perez, Maria-Josevan der Schouw, YvonneSchulze, Matthias BTjønneland, AnneWeiderpass, ElisabeteRiboli, ElioForouhi, Nita GSharp, Stephen JRolandsson, OlovWareham, Nicholas J2023-02-092023-02-092020-11-14Löfvenborg JE, Carlsson S, Andersson T, Hampe CS, Koulman A, Chirlaque Lopez MD, et al. Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study. Diabetes Care. 2021 Feb;44(2):416-424.http://hdl.handle.net/10668/16771Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes. We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed. The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative (P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs. High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.enAnimalsDietHumansAdultCohort StudiesDiabetes MellitusFatty Acids, Omega-3Fatty Acids, UnsaturatedPhospholipidsProspective Studiesresearch article33303636Restricted AccessDiabetes MellitusAdultoEstudios prospectivosEstudios de cohortesFosfolípidosÁcidos grasos Omega-3Ácidos grasos insaturados10.2337/dc20-14631935-5548PMC7818317https://europepmc.org/articles/pmc7818317?pdf=renderhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818317/pdf