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
Year: 2020
Type: other
Abstract: 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.
Authors: 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
Institution: Karolinska Institutet
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Funder: Medical Research Council
Award: G6957823285
OpenAlex ID: W4232261693