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

Research output: Contribution to journalJournal articlepeer-review

  • Josefin E. Lofvenborg
  • Sofia Carlsson
  • Tomas Andersson
  • Christiane S. Hampe
  • Albert Koulman
  • Maria Dolores Chirlaque Lopez
  • Paula Jakszyn
  • Verena A. Katzke
  • Tilman Kuhn
  • Cecilie Kyro
  • Giovanna Masala
  • Peter M. Nilsson
  • Kim Overvad
  • Salvatore Panico
  • Maria-Jose Sanchez
  • Yvonne van der Schouw
  • Matthias B. Schulze
  • Elisabete Weiderpass
  • Elio Riboli
  • Nita G. 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 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.

Original languageEnglish
JournalDiabetes Care. Supplement
Volume44
Issue number2
Pages (from-to)416-424
Number of pages9
ISSN0149-5992
DOIs
Publication statusPublished - 2021

    Research areas

  • INSULIN-RESISTANCE, RISK, AUTOANTIBODIES, AUTOIMMUNE, CANCER, POPULATION, DESIGN, EQUIVALENT, CHILDREN, VALIDITY

ID: 256314696