Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes: the EPIC-InterAct case–cohort study

Anna Maria Lampousi, Sofia Carlsson, Josefin E. Löfvenborg, Natalia Cabrera-Castro, María Dolores Chirlaque, Guy Fagherazzi, Paul W. Franks, Christiane S. Hampe, Paula Jakszyn, Albert Koulman, Cecilie Kyrø, Conchi Moreno-Iribas, Peter M. Nilsson, Salvatore Panico, Keren Papier, Yvonne T. van der Schouw, Matthias B. Schulze, Elisabete Weiderpass, Raul Zamora-Ros, Nita G. ForouhiStephen J. Sharp, Olov Rolandsson, Nicholas J. Wareham

Research output: Indexed journal article Articlepeer-review

Abstract

Aims/hypothesis: Islet autoimmunity may progress to adult-onset diabetes. We investigated whether circulating odd-chain fatty acids (OCFA) 15:0 and 17:0, which are inversely associated with type 2 diabetes, interact with autoantibodies against GAD65 (GAD65Ab) on the incidence of adult-onset diabetes. Methods: We used the European EPIC-InterAct case–cohort study including 11,124 incident adult-onset diabetes cases and a subcohort of 14,866 randomly selected individuals. Adjusted Prentice-weighted Cox regression estimated HRs and 95% CIs of diabetes in relation to 1 SD lower plasma phospholipid 15:0 and/or 17:0 concentrations or their main contributor, dairy intake, among GAD65Ab-negative and -positive individuals. Interactions between tertiles of OCFA and GAD65Ab status were estimated by proportion attributable to interaction (AP). Results: Low concentrations of OCFA, particularly 17:0, were associated with a higher incidence of adult-onset diabetes in both GAD65Ab-negative (HR 1.55 [95% CI 1.48, 1.64]) and GAD65Ab-positive (HR 1.69 [95% CI 1.34, 2.13]) individuals. The combination of low 17:0 and high GAD65Ab positivity vs high 17:0 and GAD65Ab negativity conferred an HR of 7.51 (95% CI 4.83, 11.69), with evidence of additive interaction (AP 0.25 [95% CI 0.05, 0.45]). Low dairy intake was not associated with diabetes incidence in either GAD65Ab-negative (HR 0.98 [95% CI 0.94, 1.02]) or GAD65Ab-positive individuals (HR 0.97 [95% CI 0.79, 1.18]). Conclusions/interpretation: Low plasma phospholipid 17:0 concentrations may promote the progression from GAD65Ab positivity to adult-onset diabetes. Graphical Abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)1460-1471
Number of pages12
JournalDiabetologia
Volume66
Issue number8
DOIs
Publication statusPublished - Aug 2023

Keywords

  • Diabetes
  • GAD65Ab
  • Heptadecanoic
  • Islet autoimmunity
  • OCFA
  • Pentadecanoic

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