Different types of circulating polyunsaturated fatty acids (PUFAs) are associated with differing future risk of type 2 diabetes, according to a large European study authored by Nita Forouhi of the MRC Epidemiology Unit at the University of Cambridge, United Kingdom and colleagues, and published as part of the PLOS Medicine Special Issue on Diabetes Prevention.
Most dietary guidelines recommend the consumption of polyunsaturated fatty acids for cardiovascular health, but it is unclear whether or how the individual types of omega-3 and omega-6 polyunsaturated fatty acids are related to type 2 diabetes. In particular, there is ongoing controversy on the health effects of linoleic acid, the most abundant omega-6 fatty acid.
The researchers measured circulating PUFAs in the blood samples of individuals from eight countries in Europe, who were part of EPIC-Interact, the world's largest study of new-onset type 2 diabetes. They compared baseline levels of 11 different PUFAs (4 long-chain omega-3 PUFAs and 7 omega-6 PUFAs) between 12,132 individuals who subsequently developed type 2 diabetes over a follow-up period of approximately 10 years (n=12,132) and 15,919 individuals in a sub-cohort representative of the whole EPIC study population.
After adjusting for a number of factors that might influence risk of type 2 diabetes (e.g. age, sex, body mass index, physical activity, socioeconomic status, smoking, alcohol, diet and pre-existing health conditions), they found that higher levels of omega-6 linoleic acid, which originates from diverse food sources including vegetable oils, were associated with a lower risk of future type 2 diabetes. In contrast, higher levels of four other minor individual omega-6 fatty acids were associated with higher type 2 diabetes risk, while omega-3 fatty acids typically derived from fish or seafood sources were not associated with future diabetes, and alpha linolenic acid, a plant-origin omega-3 fatty acid was associated with a lower diabetes risk.
The authors acknowledge limitations of their research including their inability to distinguish between dietary and metabolic influences on circulating blood PUFAs, the possible residual role of other factors that they accounted for in the analyses, and the observational nature of their research, but their use of blood biomarker fatty acids helps to reduce issues of measurement error that arise from using dietary self-report that relies on questionnaires. This research does not support any adverse association of the major omega-6 PUFA on the development of type 2 diabetes. By combining large-scale population data with advanced laboratory analysis, their research highlights a case to look more closely at the contribution of individual types of circulating polyunsaturated fatty acids rather than placing emphasis on the entire class of polyunsaturated fatty acids.
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Research Article
Funding:
Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following sources: Medical Research Council Epidemiology Unit MC_UU_12015/1 and MC_UU_12015/5, and Medical Research Council Human Nutrition Research MC_UP_A090_1006 and Cambridge Lipidomics Biomarker Research Initiative G0800783; TJK: Cancer Research UK; JMH and MJT: Health Research Fund of the Spanish Ministry of Health; Murcia Regional Government (N° 6236); MG: Regional Government of Navarre; -IS, DLvdA, AMWS, YTvdS: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; Verification of diabetes cases in EPIC-NL was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; RK: German Cancer Aid, German Ministry of Research (BMBF); KTK: Medical Research Council UK, Cancer Research UK; PMN: Swedish Research Council; KO and AT: Danish Cancer Society; JRQ: Asturias Regional Government; OR: The Västerboten County Council; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; ER: Imperial College Biomedical Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests:
PWF has received consulting honoraria from Ely Lily & Co and Sanofi Aventis. CL receives a stipend as a specialty consulting editor for PLOS Medicine and serves on the journal's editorial board. NJW served as a guest editor on PLOS Medicine's Diabetes Prevention Special Issue.
Citation:
Forouhi NG, Imamura F, Sharp SJ, Koulman A, Schulze MB, Zheng J, et al. (2016) Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study. PLoS Med 13(7): e1002094. doi:10.1371/journal.pmed.1002094
Author Affiliations:
MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom
MRC Human Nutrition Research, Cambridge, UK
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany
University Medical Center Utrecht, Utrecht, the Netherlands
Navarre Public Health Institute (ISPN), Pamplona, Spain
CIBER Epidemiología y Salud Pública (CIBERESP), Spain
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
Wageningen University, The Netherlands
Inserm, CESP, U1018, Villejuif, France
Univ Paris-Sud, UMRS 1018, Villejuif, France
Gustave Roussy Institute, Villejuif, France
Public Health Division of Gipuzkoa, San Sebastian, Spain
Instituto BIO-Donostia, Basque Government, San Sebastian, Spain
German Institute of Human Nutrition Potsdam-Rehbruecke, Germany
Lund University, Malmö, Sweden
Umeå University, Umeå, Sweden
Catalan Institute of Oncology (ICO), Barcelona, Spain
German Cancer Research Centre (DKFZ), Heidelberg, Germany
University of Oxford, Oxford, United Kingdom
University of Cambridge, Cambridge, United Kingdom
Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark
Aalborg University Hospital, Aalborg, Denmark
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Cancer Research and Prevention Institute (ISPO), Florence, Italy
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
Public Health Directorate, Asturias, Spain
Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital-University of Turin and Center for Cancer Prevention (CPO), Turin, Italy
Human Genetics Foundation (HuGeF), Turin, Italy
International Agency for Research on Cancer, Lyon, France
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Danish Cancer Society Research Center, Copenhagen, Denmark
Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain
Cancer Registry and Histopathology Unit, Civic and M.P.Arezzo Hospital, ASP Ragusa, Italy
School of Public Health, Imperial College London, London, United Kingdom
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