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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

Löfvenborg, Josefin E. ; Carlsson, Sofia ; Andersson, Tomas ; Hampe, Christiane S. ; Koulman, Albert ; Lopez, María Dolores Chirlaque ; Jakszyn, Paula ; Katzke, Verena A. ; Kühn, Tilman and Kyrø, Cecilie , et al. (2021) In Diabetes Care 44(2). p.416-424
Abstract

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... (More)

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 5 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.

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type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
44
issue
2
pages
9 pages
publisher
American Diabetes Association
external identifiers
  • pmid:33303636
  • scopus:85099979256
ISSN
0149-5992
DOI
10.2337/dc20-1463
language
English
LU publication?
yes
id
ff505ed1-9baa-4b9e-a0ee-01661c690eb8
date added to LUP
2021-02-05 13:50:09
date last changed
2021-05-11 02:56:23
@article{ff505ed1-9baa-4b9e-a0ee-01661c690eb8,
  abstract     = {<p>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 5 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.</p>},
  author       = {Löfvenborg, Josefin E. and Carlsson, Sofia and Andersson, Tomas and Hampe, Christiane S. and Koulman, Albert and Lopez, María Dolores Chirlaque and Jakszyn, Paula and Katzke, Verena A. and Kühn, Tilman and Kyrø, Cecilie and Masala, Giovanna and Nilsson, Peter M. and Overvad, Kim and Panico, Salvatore and Sánchez, Maria Jose and Van Der Schouw, Yvonne and Schulze, Matthias B. and Tjønneland, Anne and Weiderpass, Elisabete and Riboli, Elio and Forouhi, Nita G. and Sharp, Stephen J. and Rolandsson, Olov and Wareham, Nicholas J.},
  issn         = {0149-5992},
  language     = {eng},
  number       = {2},
  pages        = {416--424},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {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},
  url          = {http://dx.doi.org/10.2337/dc20-1463},
  doi          = {10.2337/dc20-1463},
  volume       = {44},
  year         = {2021},
}