American Diabetes Association
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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

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posted on 2020-12-10, 19:07 authored by Josefin E Löfvenborg, Sofia Carlsson, Tomas Andersson, Christiane S Hampe, Albert Koulman, María Dolores Chirlaque Lopez, Paula Jakszyn, Verena A Katzke, Tilman Kühn, Cecilie Kyrø, Giovanna Masala, Peter M Nilsson, Kim Overvad, Salvatore Panico, Maria-Jose Sánchez, Yvonne van der Schouw, Matthias B. Schulze, Anne Tjønneland, Elisabete Weiderpass, Elio Riboli, Nita Forouhi, Stephen J Sharp, Olov Rolandsson, Nicholas J Wareham
Objective: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid polyunsaturated omega-3 fatty acid (n-3 PUFA) concentration with GAD65 antibody positivity on the risk of developing adult onset diabetes.

Research Design and Methods: We used prospective data on 11,247 incident cases of adult onset diabetes and 14,288 non-cases 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 interaction between GAD65 antibody positivity (≥65 U/ml) and low fish/n-3 PUFA were assessed.

Results: 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; 2.48, 1.79-3.45) compared to people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44, 95% CI 0.16-0.72; 0.48, 0.24-0.72) and multiplicative (p=0.0465; 0.0103) interaction. Individuals with high GAD65 antibody levels (≥167.5 U/ml) and low total plasma phospholipid n-3 PUFA had more than 4-fold higher hazard of diabetes (HR 4.26, 2.70-6.72), AP 0.46 (0.12-0.80), compared to antibody negative individuals with high n-3 PUFA.

Conclusions: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.


The EPIC-InterAct project was funded by the European Union FP6 programme (grant no. LSHM_CT_2006_037197). Measurements of GAD65 antibodies was funded by Västerbotten County Council and Umeå University, Sweden (OR), the National Institutes of Health (DK26190) (CSH), and by the Medical Research Council (MC_UU_12015/1) (NJW). NGF is funded by the Medical Research Council (MC_UU_12015/5) and NJW, AK, and NGF by the NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014). JEL, SC, and TA were supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Research Council, Novo Nordisk Foundation, Swedish Nutrition Foundation, and Swedish Diabetes Foundation. PJ received institutional support from CERCA Programme/Generalitat de Catalunya.