TY - JOUR
T1 - Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes
T2 - the EPIC-InterAct case-cohort study
AU - Lampousi, Anna-Maria
AU - Carlsson, Sofia
AU - Löfvenborg, Josefin E
AU - Cabrera-Castro, Natalia
AU - Chirlaque, María-Dolores
AU - Fagherazzi, Guy
AU - Franks, Paul W
AU - Hampe, Christiane S
AU - Jakszyn, Paula
AU - Koulman, Albert
AU - Kyrø, Cecilie
AU - Moreno-Iribas, Conchi
AU - Nilsson, Peter M
AU - Panico, Salvatore
AU - Papier, Keren
AU - van der Schouw, Yvonne T
AU - Schulze, Matthias B
AU - Weiderpass, Elisabete
AU - Zamora-Ros, Raul
AU - Forouhi, Nita G
AU - Sharp, Stephen J
AU - Rolandsson, Olov
AU - Wareham, Nicholas J
N1 - Funding Information:
The EPIC-InterAct project was funded by the European Union FP6 programme (grant no. LSHM_CT_2006_037197). Measurements of GAD65Ab were funded by the National Institutes of Health grant DK-26190 (CSH), Västerbotten County Council and Umeå University (OR) and Medical Research Council grant MC_UU_12015/1 (NJW). A-ML, SC and JEL were supported by the Swedish Research Council for Health, Working Life and Welfare (FORTE, 2018-00337), Novo Nordisk Foundation (NNF19OC0057274), Swedish Research Council (2018-03035) and Swedish Diabetes Foundation (DIA2022-735). RZ-R was supported by the ‘Miguel Servet II’ (CPII20/00009) programme from the Institute of Health Carlos III (co-funded by European Social Fund [ESF] investing in your future). MBS was supported by a grant from the German Federal Ministry of Education and Research and the State of Brandenburg to the German Center for Diabetes Research (DZD) (82DZD03D03). NGF and NJW acknowledge support from the MRC Epidemiology Unit (grants MC_UU_00006/1 and MC_UU_00006/3). NGF, AK and NJW acknowledge support from the National Institute of Health and Care Research (NIHR) Cambridge Biomedical Research Centre (NIHR203312), and NGF is an NIHR Senior Investigator. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The study funders were not involved in the design of the study; the collection, analysis and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report. Open access funding was provided by Karolinska Institutet.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/8
Y1 - 2023/8
N2 - 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.]
AB - 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.]
KW - Diabetes
KW - GAD65Ab
KW - Heptadecanoic
KW - Islet autoimmunity
KW - OCFA
KW - Pentadecanoic
UR - http://www.scopus.com/inward/record.url?scp=85161458065&partnerID=8YFLogxK
U2 - 10.1007/s00125-023-05948-x
DO - 10.1007/s00125-023-05948-x
M3 - Article
C2 - 37301794
SN - 0012-186X
VL - 66
SP - 1460
EP - 1471
JO - Diabetologia
JF - Diabetologia
IS - 8
ER -