1. Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes: the EPIC-InterAct case-cohort study
- Author
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Lampousi, Anna-Maria, Carlsson, Sofia, Löfvenborg, Josefin E., Cabrera-Castro, Natalia, Chirlaque, María-Dolores, Fagherazzi, Guy, Franks, Paul W., Hampe, Christiane S., Jakszyn, Paula, Koulman, Albert, Kyrø, Cecilie, Moreno-Iribas, Conchi, Nilsson, Peter M., Panico, Salvatore, Papier, Keren, van der Schouw, Yvonne T., Schulze, Matthias B., Weiderpass, Elisabete, Zamora-Ros, Raul, Forouhi, Nita G., Sharp, Stephen J., Rolandsson, Olov, Wareham, Nicholas J., Lampousi, Anna-Maria [0000-0002-3640-3827], Carlsson, Sofia [0000-0002-9497-2331], Löfvenborg, Josefin E [0000-0002-0099-969X], Chirlaque, María-Dolores [0000-0001-9242-3040], Fagherazzi, Guy [0000-0001-5033-5966], Franks, Paul W [0000-0002-0520-7604], Hampe, Christiane S [0000-0001-9111-6671], Jakszyn, Paula [0000-0003-0672-8847], Koulman, Albert [0000-0001-9998-051X], Kyrø, Cecilie [0000-0002-9083-8960], Moreno-Iribas, Conchi [0000-0001-6537-0131], Nilsson, Peter M [0000-0002-5652-8459], Panico, Salvatore [0000-0002-5498-8312], Papier, Keren [0000-0002-4102-6835], van der Schouw, Yvonne T [0000-0002-4605-435X], Schulze, Matthias B [0000-0002-0830-5277], Weiderpass, Elisabete [0000-0003-2237-0128], Zamora-Ros, Raul [0000-0002-6236-6804], Forouhi, Nita G [0000-0002-5041-248X], Sharp, Stephen J [0000-0003-2375-1440], Rolandsson, Olov [0000-0002-1341-6828], Wareham, Nicholas J [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
- Subjects
Adult ,Glutamate Decarboxylase ,Incidence ,Diabetes ,Heptadecanoic ,Fatty Acids ,Endocrinology and Diabetes ,GAD65Ab ,OCFA ,Cohort Studies ,Pentadecanoic ,Diabetes Mellitus, Type 2 ,Endokrinologi och diabetes ,Humans ,Islet autoimmunity ,Phospholipids ,Autoantibodies - 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.]
- Published
- 2023