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: article
Abstract: OBJECTIVE Islet 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. RESEARCH DESIGN AND METHODS 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. 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] 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. CONCLUSIONS High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.
Source: Diabetes Care
DOI: 10.2337/dc20-1463
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 G. Forouhi, Stephen J. Sharp, Olov Rolandsson, Nicholas J. Wareham
Institutions: Karolinska Institutet, Region Stockholm, University of Washington, University of Cambridge, National Institute for Health and Care Research, MRC Epidemiology Unit, NIHR Cambridge Biomedical Research Centre, Medical Research Council, Instituto Murciano de Investigación Biosanitaria, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Universidad de Murcia, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Universitat Ramon Llull, German Cancer Research Center, Danish Cancer Society, Lund University, Aarhus University, Aalborg University Hospital, Federico II University Hospital, University of Naples Federico II, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Andalusian School of Public Health, University Medical Center Utrecht, University of Potsdam, German Center for Diabetes Research, German Institute of Human Nutrition, University of Copenhagen, Centre international de recherche sur le cancer, Imperial College London, Umeå University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: World Health Organization, Centre International de Recherche sur le Cancer, Centres de Recerca de Catalunya, National Institute for Health and Care Research, European Commission, Generalitat de Catalunya, Västerbotten Läns Landsting, Novo Nordisk, Vetenskapsrådet, Umeå Universitet, Forskningsrådet om Hälsa, Arbetsliv och Välfärd, Diabetesförbundet, Novo Nordisk Fonden, National Institutes of Health, Medical Research Council, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1075599542, Aetiology of type 2 diabetes and related metabolic disorders, Nutritional epidemiology, G1406068971, G223563082, G2826529823, G2892497062, G299057155, G3417074193, G370598735, NIHR Senior Investigator Award, G485284085, G6206044308, Islet Cell Membrane Antibodies in Diabetes, G6641991021, G6957823285, NIHR Senior Investigator Award
OpenAlex ID: W3111482582