Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes : the EPIC-InterAct case–cohort study
(2023) In Diabetologia 66(8). p.1460-1471- 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... (More)
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.]
(Less)
- author
- organization
- publishing date
- 2023-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Diabetes, GAD65Ab, Heptadecanoic, Islet autoimmunity, OCFA, Pentadecanoic
- in
- Diabetologia
- volume
- 66
- issue
- 8
- pages
- 12 pages
- publisher
- Springer
- external identifiers
-
- pmid:37301794
- scopus:85161458065
- ISSN
- 0012-186X
- DOI
- 10.1007/s00125-023-05948-x
- language
- English
- LU publication?
- yes
- id
- fb388517-8f06-4edb-b1ca-c25546be83ee
- date added to LUP
- 2023-08-23 10:28:41
- date last changed
- 2024-09-07 14:32:46
@article{fb388517-8f06-4edb-b1ca-c25546be83ee,
abstract = {{<p>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.]</p>}},
author = {{Lampousi, Anna Maria and Carlsson, Sofia and Löfvenborg, Josefin E. and Cabrera-Castro, Natalia and Chirlaque, María Dolores and Fagherazzi, Guy and Franks, Paul W. and Hampe, Christiane S. and Jakszyn, Paula and Koulman, Albert and Kyrø, Cecilie and Moreno-Iribas, Conchi and Nilsson, Peter M. and Panico, Salvatore and Papier, Keren and van der Schouw, Yvonne T. and Schulze, Matthias B. and Weiderpass, Elisabete and Zamora-Ros, Raul and Forouhi, Nita G. and Sharp, Stephen J. and Rolandsson, Olov and Wareham, Nicholas J.}},
issn = {{0012-186X}},
keywords = {{Diabetes; GAD65Ab; Heptadecanoic; Islet autoimmunity; OCFA; Pentadecanoic}},
language = {{eng}},
number = {{8}},
pages = {{1460--1471}},
publisher = {{Springer}},
series = {{Diabetologia}},
title = {{Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes : the EPIC-InterAct case–cohort study}},
url = {{http://dx.doi.org/10.1007/s00125-023-05948-x}},
doi = {{10.1007/s00125-023-05948-x}},
volume = {{66}},
year = {{2023}},
}