TY - JOUR
T1 - Interaction between gad65 antibodies and dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acids on incident adult-onset diabetes
T2 - The epic-interact study
AU - Löfvenborg, Josefin E.
AU - Carlsson, Sofia
AU - Andersson, Tomas
AU - Hampe, Christiane S.
AU - Koulman, Albert
AU - Lopez, María Dolores Chirlaque
AU - Jakszyn, Paula
AU - Katzke, Verena A.
AU - Kühn, Tilman
AU - Kyrø, Cecilie
AU - Masala, Giovanna
AU - Nilsson, Peter M.
AU - Overvad, Kim
AU - Panico, Salvatore
AU - Sánchez, Maria Jose
AU - Van Der Schouw, Yvonne
AU - Schulze, Matthias B.
AU - Tjønneland, Anne
AU - Weiderpass, Elisabete
AU - Riboli, Elio
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 number LSHM_CT_2006_037197). Measurements of GAD65 antibodies was funded by National Institutes of Health grant DK-26190 (C.S.H.), Västerbotten County Council and Umeå University (O.R.), and Medical Research Council grant MC_UU_12015/1 (N.J.W.). J.E.L., S.C., and T.A. were supported by the Swedish Research Council for Health, Working Life and Welfare, Novo Nordisk Foundation, Swedish Research Council, Swedish Nutrition Foundation, and Swedish Diabetes Foundation. A.K., N.G.F., and N.J.W. are funded by the NIHRBiomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014) and N.G.F. by Medical Research Council grant MC_UU_12015/5. P.J. received institutional support from CERCA Programme/Generalitat de Catalunya.
Funding Information:
Acknowledgments. The authors thank all EPIC participants and staff for their contributions. The authors also thank Nicola Kerrison (Medical Research Council Epidemiology Unit) for managing thedatafortheInterActprojectandtheCambridge Medical Research Council Epidemiology Unit laboratory team for managing the blood samples. Funding. The EPIC-InterAct project was funded by the European Union FP6 programme (grant number LSHM_CT_2006_037197). Measurements of GAD65 antibodies was funded by National Institutes of Health grant DK-26190 (C.S.H.), Västerbotten County Council and Umeå University (O.R.), and Medical Research Council grant MC_UU_ 12015/1 (N.J.W.). J.E.L., S.C., andT.A.were supported by the Swedish Research Council for Health, Working Life and Welfare, Novo Nordisk Foundation, Swedish Research Council, Swedish Nutrition Foundation, and Swedish Diabetes Foundation. A.K., N.G.F., and N.J.W. are funded by the NIHR Biomedical Research Centre Cambridge:Nutrition,Diet,and Lifestyle Research Theme (IS-BRC-1215-20014) and N.G.F. by Medical Research Council grant MC_UU_12015/5. P.J. received institutional support from CERCA Programme/Generalitat de Catalunya. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. J.E.L. performed the statistical analyses and drafted the manuscript.
Publisher Copyright:
© 2020 by the American Diabetes Association.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85099979256&partnerID=8YFLogxK
U2 - 10.2337/dc20-1463
DO - 10.2337/dc20-1463
M3 - Article
C2 - 33303636
AN - SCOPUS:85099979256
SN - 0149-5992
VL - 44
SP - 416
EP - 424
JO - Diabetes Care
JF - Diabetes Care
IS - 2
ER -