SEARCHCOHORTendocrinology, nutrition

cohort·endocrinology, nutrition, epidemiology, internal medicine, public health·PMC10317878

Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes: the EPIC-InterAct case–cohort study

Diabetologia · 23 authors, 23 centres

AI SUMMARY

FIDELITY 100%

POPULATIONEuropean adults from the EPIC-InterAct case–cohort study, including 11,124 incident adult-onset diabetes cases and a subcohort of 14,866 randomly selected individuals.

INTERVENTIONPlasma phospholipid concentrations of odd-chain fatty acids (15:0 and 17:0) and dairy intake.

COMPARISONStratification by GAD65 autoantibody (GAD65Ab) status (negative vs. positive).

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AGENT 01 · STRUCTURED SUMMARY

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TL;DR

This large European cohort study investigated whether low plasma odd-chain fatty acids, particularly 17:0, interact with GAD65 autoantibodies to affect the risk of developing adult-onset diabetes. The central result was that low 17:0 combined with positive GAD65Ab status was associated with a substantially higher diabetes risk, showing evidence of additive interaction.

Full summary

986 CHARS

The study used a case–cohort design within the European EPIC-InterAct study to examine associations between plasma phospholipid odd-chain fatty acids (OCFA 15:0 and 17:0), dairy intake, and incident adult-onset diabetes, considering GAD65Ab status. Among 11,124 cases and a subcohort of 14,866 individuals, low 17:0 was associated with higher diabetes incidence in both GAD65Ab-negative (HR 1.55) and GAD65Ab-positive (HR 1.69) individuals. The combination of low 17:0 and high GAD65Ab positivity conferred a hazard ratio of 7.51 compared to high 17:0 and GAD65Ab negativity, with evidence of additive interaction (AP 0.25). Low dairy intake was not associated with diabetes incidence. Limitations include potential measurement errors, residual confounding, and the fact that autoantibody status and exposures were only assessed at baseline. The findings suggest that low 17:0 may promote progression from GAD65Ab positivity to diabetes, highlighting a potential modifiable risk factor.

PICO

PPOPULATION

European adults from the EPIC-InterAct case–cohort study, including 11,124 incident adult-onset diabetes cases and a subcohort of 14,866 randomly selected individuals.

IINTERVENTION

Plasma phospholipid concentrations of odd-chain fatty acids (15:0 and 17:0) and dairy intake.

OOUTCOME

Incidence of adult-onset diabetes over an 11-year follow-up period.

STUDY TYPE

cohort

SPECIALTY

endocrinology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10317878

Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes: the EPIC-InterAct case–cohort study

Diabetologia

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ABSTRACT

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 Supplementary Information The online version of this article (10.1007/s00125-023-05948-x) contains peer-reviewed but unedited supplementary material. Keywords: Diabetes, GAD65Ab, Heptadecanoic, Islet autoimmunity, OCFA, Pentadecanoic

CITATION EXPORT

Anna-Maria Lampousi, Sofia Carlsson, Josefin E Löfvenborg et al.. Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes: the EPIC-InterAct case–cohort study. Diabetologia. (2023). https://doi.org/10.1007/s00125-023-05948-x

AUTHORS

23 · 23 CENTRES

Anna-Maria Lampousi, Sofia Carlsson, Josefin E Löfvenborg, Natalia Cabrera-Castro, María-Dolores Chirlaque, Guy Fagherazzi, Paul W Franks, Christiane S Hampe, Paula Jakszyn, Albert Koulman, Cecilie Kyrø, Conchi Moreno-Iribas, Peter M Nilsson, Salvatore Panico, Keren Papier, Yvonne T van der Schouw, Matthias B Schulze, Elisabete Weiderpass, Raul Zamora-Ros, Nita G Forouhi, Stephen J Sharp, Olov Rolandsson, Nicholas J Wareham

1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
2Department of Risk and Benefit Assessment, Swedish Food Agency, Uppsala, Sweden
3Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain
4Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
5Department of Health and Social Sciences, Murcia University, Murcia, Spain
6Deep Digital Phenotyping Research Unit, Department of Precision Health, Luxembourg Institute of Health, Strassen, Luxembourg
7Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, Malmö, Sweden
8Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, Umeå, Sweden
9Department of Medicine, University of Washington School of Medicine, Seattle, WA USA
10Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
11Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain
12Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK
13National Institute for Health Research Biomedical Research Centre Core Nutritional Biomarker Laboratory, University of Cambridge School of Clinical Medicine, Cambridge, UK
14Danish Cancer Society Research Center, Copenhagen, Denmark
15Navarra Public Health Institute, Pamplona, Spain
16Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
17Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
18Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
19Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
20Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
21German Center for Diabetes Research (DZD), Neuherberg, Germany
22Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
23International Agency for Research on Cancer, World Health Organization, Lyon, France