Articles Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies
Y Wu
(1)
,
Matti Marklund
(2)
,
Fumiaki Imamura
(3)
,
Nathan Tintle
(4)
,
Ardisson Korat
(5)
,
Janette de Goede
(6)
,
Xia Zhou
(7)
,
Wei-Sin Yang
(8)
,
Marcia C de Oliveira Otto
(9)
,
Janine Kröger
(10)
,
Waqas Qureshi
(11)
,
Jyrki K Virtanen
(12)
,
Julie K Bassett
(13)
,
Alexis C Frazier-Wood
(14)
,
Maria Lankinen
(12)
,
Rachel A Murphy
(15)
,
Kalina Rajaobelina
(16)
,
Del Gobbo
(17)
,
Nita G Forouhi
(3)
,
Robert Luben
(18)
,
Kay-Tee Khaw
(18, 4)
,
Nick Wareham
(3)
,
Anya Kalsbeek
(4, 19)
,
Jenna Veenstra
(4, 19)
,
Juhua Luo
(20)
,
Frank B Hu
(5)
,
Hung-Ju Lin
(21)
,
David S Siscovick
(22)
,
Heiner Boeing
(10)
,
Tzu-An Chen
(14)
,
Brian Steffen
(23)
,
Lyn M Steffen
(7)
,
Allison Hodge
(13)
,
Gudny Eriksdottir
(24)
,
Albert V Smith
(24)
,
Vilmunder Gudnason
(24)
,
Tamara B Harris
(25)
,
Ingeborg A Brouwer
(26)
,
Claudine Berr
(27)
,
Catherine Helmer
(16)
,
Cecilia Samieri
(16)
,
Markku Laakso
(28)
,
Michael y Tsai
(7)
,
Graham G Giles
(13)
,
Tarja Nurmi
(12)
,
Lynne Wagenknecht
(11)
,
Matthias B Schulze
(10)
,
Rozenn N Lemaitre
(29)
,
Kuo-Liong Chien
(8, 30)
,
Sabita S Soedamah-Muthu
(6)
,
Johanna M Geleijnse
(6)
,
Qi Sun
(5)
,
William S Harris
(31, 32)
,
Lars Lind
(33)
,
Johan Ärnlöv
(34, 35)
,
Ulf Riserus
(2)
,
Renata Micha
(36)
,
Dariush Mozaffarian
(36)
1
GIGH -
The George Institute for Global Health [Sydney]
2 Clinical Nutrition and Metabolism - Department of Public Health and Caring Sciences [Uppsala, Sweden]
3 Medical Research Council Epidemiology Unit [Cambridge, UK]
4 Department of Mathematics and Statistics [Sioux Center, IA, USA]
5 Departments of Epidemiology and Nutrition [Boston, MA, USA]
6 Division of Human Nutrition [Wageningen, Netherlands]
7 School of Public Health [Minneapolis, MN, États-Unis]
8 Institute of Epidemiology and Preventive Medicine [Taipei, Taiwan]
9 Division of Epidemiology - Human Genetics and Environmental Sciences [Houston, TX, USA]
10 DIfE - German Institute of Human Nutrition Potsdam-Rehbrücke
11 Wake Forest University
12 Institute of Public Health and Clinical Nutrition [Kuopio, Finland]
13 Cancer Council Victoria
14 US Department of Agriculture/Agricultural Research Service [Houston, TX, USA]
15 UBC - University of British Columbia [Canada]
16 BPH - Bordeaux population health
17 Stanford Medicine
18 Institute of Public Health - Department of Public Health and Primary Care [Cambridge, UK]
19 Department of Biology [Sioux Center, IA, USA]
20 Department of Epidemiology and Biostatistics [Bloomington, IN, USA]
21 School of Medicine [Taipei, Taiwan]
22 The New York Academy of Medicine [New York, NY, USA]
23 Department of Laboratory Medicine and Pathology [Minneapolis, MN, USA]
24 Icelandic Heart Institute [Kópavogur, Iceland]
25 NIA - National Institute on Aging [Bethesda, USA]
26 Athena Institute for Research on Innovation and Communication in Health and Life Sciences [Amsterdam, Pays-Bas]
27 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
28 Institute of Clinical Medicine [Kuopio, Finland]
29 Department of Medicine - Cardiovascular Health Research Unit [Seattle, WA, USA]
30 Department of Internal Medicine [Taipei, Taiwan]
31 Sanford School of Medicine - Department of Internal Medicine [Sioux Falls, SD, USA]
32 OmegaQuant Analytics [Sioux Falls, SD, USA]
33 Department of Medical Sciences [Uppsala, Sweden]
34 Division of Family Medicine - Department of Neurobiology, Care Sciences and Society [Stockholm, Sweden]
35 School of Health and Social Studies [Falun, Sweden]
36 Friedman School of Nutrition Science and Policy [Boston, MA, USA]
2 Clinical Nutrition and Metabolism - Department of Public Health and Caring Sciences [Uppsala, Sweden]
3 Medical Research Council Epidemiology Unit [Cambridge, UK]
4 Department of Mathematics and Statistics [Sioux Center, IA, USA]
5 Departments of Epidemiology and Nutrition [Boston, MA, USA]
6 Division of Human Nutrition [Wageningen, Netherlands]
7 School of Public Health [Minneapolis, MN, États-Unis]
8 Institute of Epidemiology and Preventive Medicine [Taipei, Taiwan]
9 Division of Epidemiology - Human Genetics and Environmental Sciences [Houston, TX, USA]
10 DIfE - German Institute of Human Nutrition Potsdam-Rehbrücke
11 Wake Forest University
12 Institute of Public Health and Clinical Nutrition [Kuopio, Finland]
13 Cancer Council Victoria
14 US Department of Agriculture/Agricultural Research Service [Houston, TX, USA]
15 UBC - University of British Columbia [Canada]
16 BPH - Bordeaux population health
17 Stanford Medicine
18 Institute of Public Health - Department of Public Health and Primary Care [Cambridge, UK]
19 Department of Biology [Sioux Center, IA, USA]
20 Department of Epidemiology and Biostatistics [Bloomington, IN, USA]
21 School of Medicine [Taipei, Taiwan]
22 The New York Academy of Medicine [New York, NY, USA]
23 Department of Laboratory Medicine and Pathology [Minneapolis, MN, USA]
24 Icelandic Heart Institute [Kópavogur, Iceland]
25 NIA - National Institute on Aging [Bethesda, USA]
26 Athena Institute for Research on Innovation and Communication in Health and Life Sciences [Amsterdam, Pays-Bas]
27 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
28 Institute of Clinical Medicine [Kuopio, Finland]
29 Department of Medicine - Cardiovascular Health Research Unit [Seattle, WA, USA]
30 Department of Internal Medicine [Taipei, Taiwan]
31 Sanford School of Medicine - Department of Internal Medicine [Sioux Falls, SD, USA]
32 OmegaQuant Analytics [Sioux Falls, SD, USA]
33 Department of Medical Sciences [Uppsala, Sweden]
34 Division of Family Medicine - Department of Neurobiology, Care Sciences and Society [Stockholm, Sweden]
35 School of Health and Social Studies [Falun, Sweden]
36 Friedman School of Nutrition Science and Policy [Boston, MA, USA]
Fumiaki Imamura
- Fonction : Auteur
- PersonId : 799678
- ORCID : 0000-0002-6841-8396
Lars Lind
- Fonction : Auteur
- PersonId : 773565
- ORCID : 0000-0003-2335-8542
Johan Ärnlöv
- Fonction : Auteur
- PersonId : 773561
- ORCID : 0000-0002-6933-4637
Résumé
BACKGROUND:
The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes.
METHODS:
We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis.
FINDINGS:
Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m2, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60-0·72, p<0·0001; I2=53·9%, pheterogeneity=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88-1·05; p=0·38; I2=63·0%, pheterogeneity<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all pheterogeneity≥0·13).
INTERPRETATION:
Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.
FUNDING:
Funders are shown in the appendix.
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