TY - JOUR
T1 - Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes
T2 - The EPIC-InterAct case-cohort study
AU - Forouhi, Nita G.
AU - Koulman, Albert
AU - Sharp, Stephen J.
AU - Imamura, Fumiaki
AU - Kröger, Janine
AU - Schulze, Matthias B.
AU - Crowe, Francesca L.
AU - Huerta, José María
AU - Guevara, Marcela
AU - Beulens, Joline W.J.
AU - van Woudenbergh, Geertruida J.
AU - Wang, Laura
AU - Summerhill, Keith
AU - Griffin, Julian L.
AU - Feskens, Edith J.M.
AU - Amiano, Pilar
AU - Boeing, Heiner
AU - Clavel-Chapelon, Françoise
AU - Dartois, Laureen
AU - Fagherazzi, Guy
AU - Franks, Paul W.
AU - Gonzalez, Carlos
AU - Jakobsen, Marianne Uhre
AU - Kaaks, Rudolf
AU - Key, Timothy J.
AU - Khaw, Kay Tee
AU - Kühn, Tilman
AU - Mattiello, Amalia
AU - Nilsson, Peter M.
AU - Overvad, Kim
AU - Pala, Valeria
AU - Palli, Domenico
AU - Quirós, J. Ramón
AU - Rolandsson, Olov
AU - Roswall, Nina
AU - Sacerdote, Carlotta
AU - Sánchez, María José
AU - Slimani, Nadia
AU - Spijkerman, Annemieke M.W.
AU - Tjonneland, Anne
AU - Tormo, Maria José
AU - Tumino, Rosario
AU - van der A, Daphne L.
AU - van der Schouw, Yvonne T.
AU - Langenberg, Claudia
AU - Riboli, Elio
AU - Wareham, Nicholas J.
N1 - Funding Information:
Funding for the InterAct project was provided by the EU FP6 programme ( grant number LSHM_CT_2006_037197 ). Additionally, InterAct investigators acknowledge funding from the following sources: Medical Research Council Epidemiology Unit ( grants MC_UU_12015/1 and MC_UU_12015/5 ), Medical Research Council Human Nutrition Research ( grant MC_UD99999906 ), and Cambridge Lipidomics Biomarker Research Initiative ( grant G0800783 ) (to AK, LW, KS, and JLG); Cancer Research UK (to FLC and TJK); Health Research Fund of the Spanish Ministry of Health (to JMH and MJT); Murcia Regional Government (no. 6236, to JMH); Regional Government of Navarre (to MG); the Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Dutch ZON, World Cancer Research Fund, and Statistics Netherlands (to JWJB, DLvdA, AMWS, and YTvdS); Swedish Research Council (to PWF and PMN); Novo Nordisk, Swedish Diabetes Association, and the Swedish Heart-Lung Foundation (to PWF); German Cancer Aid and German Ministry of Research (to RK); Medical Research Council UK and Cancer Research UK (to KTK); Danish Cancer Society (to KO and AT); Asturias Regional Government (to JRQ); The Västerboten County Council (to OR); AIRE-ONLUS Ragusa, AVIS-Ragusa, and Sicilian Regional Government (to RT); and Imperial College Biomedical Research Centre (to ER). Verification of diabetes cases in EPIC-NL was additionally funded by NL Agency grant IGE05012 and an incentive grant from the board of the University Medical Centre Utrecht. We thank all EPIC participants and staff for their contribution to the study; the laboratory teams at the Medical Research Council Epidemiology Unit for sample management and at Medical Research Council Human Nutrition Research for biochemical analysis; and Nicola Kerrison for data management. None of the staff received any compensation for their contributions.
Funding Information:
JMH has received grants from the Health Research Fund (Spanish Ministry of Health) and from the Murcia Regional Government ( grant no. 6236 ). The other authors declare no competing interests.
Publisher Copyright:
© 2014 Forouhi et al. Open Access article distributed under the terms of CC BY.
PY - 2014
Y1 - 2014
N2 - Background: Conflicting evidence exists regarding the association between saturated fatty acids (SFAs) and type 2 diabetes. In this longitudinal case-cohort study, we aimed to investigate the prospective associations between objectively measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants. Methods: The EPIC-InterAct case-cohort study includes 12 403 people with incident type 2 diabetes and a representative subcohort of 16 154 individuals who were selected from a cohort of 340 234 European participants with 3·99 million person-years of follow-up (the EPIC study). Incident type 2 diabetes was ascertained until Dec 31, 2007, by a review of several sources of evidence. Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids (mol%); samples from people with type 2 diabetes and subcohort participants were processed in a random order by centre, and laboratory staff were masked to participant characteristics. We estimated country-specific hazard ratios (HRs) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression, which is weighted for case-cohort sampling, and pooled our findings using random-effects meta-analysis. Findings: SFAs accounted for 46% of total plasma phospholipid fatty acids. In adjusted analyses, different individual SFAs were associated with incident type 2 diabetes in opposing directions. Even-chain SFAs that were measured (14:0 [myristic acid], 16:0 [palmitic acid], and 18:0 [stearic acid]) were positively associated with incident type 2 diabetes (HR [95% CI] per SD difference: myristic acid 1·15 [95% CI 1·09-1·22], palmitic acid 1·26 [1·15-1·37], and stearic acid 1·06 [1·00-1·13]). By contrast, measured odd-chain SFAs (15:0 [pentadecanoic acid] and 17:0 [heptadecanoic acid]) were inversely associated with incident type 2 diabetes (HR [95% CI] per 1 SD difference: 0·79 [0·73-0·85] for pentadecanoic acid and 0·67 [0·63-0·71] for heptadecanoic acid), as were measured longer-chain SFAs (20:0 [arachidic acid], 22:0 [behenic acid], 23:0 [tricosanoic acid], and 24:0 [lignoceric acid]), with HRs ranging from 0·72 to 0·81 (95% CIs ranging between 0·61 and 0·92). Our findings were robust to a range of sensitivity analyses. Interpretation: Different individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions, which suggests that SFAs are not homogeneous in their effects. Our findings emphasise the importance of the recognition of subtypes of these fatty acids. An improved understanding of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed.
AB - Background: Conflicting evidence exists regarding the association between saturated fatty acids (SFAs) and type 2 diabetes. In this longitudinal case-cohort study, we aimed to investigate the prospective associations between objectively measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants. Methods: The EPIC-InterAct case-cohort study includes 12 403 people with incident type 2 diabetes and a representative subcohort of 16 154 individuals who were selected from a cohort of 340 234 European participants with 3·99 million person-years of follow-up (the EPIC study). Incident type 2 diabetes was ascertained until Dec 31, 2007, by a review of several sources of evidence. Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids (mol%); samples from people with type 2 diabetes and subcohort participants were processed in a random order by centre, and laboratory staff were masked to participant characteristics. We estimated country-specific hazard ratios (HRs) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression, which is weighted for case-cohort sampling, and pooled our findings using random-effects meta-analysis. Findings: SFAs accounted for 46% of total plasma phospholipid fatty acids. In adjusted analyses, different individual SFAs were associated with incident type 2 diabetes in opposing directions. Even-chain SFAs that were measured (14:0 [myristic acid], 16:0 [palmitic acid], and 18:0 [stearic acid]) were positively associated with incident type 2 diabetes (HR [95% CI] per SD difference: myristic acid 1·15 [95% CI 1·09-1·22], palmitic acid 1·26 [1·15-1·37], and stearic acid 1·06 [1·00-1·13]). By contrast, measured odd-chain SFAs (15:0 [pentadecanoic acid] and 17:0 [heptadecanoic acid]) were inversely associated with incident type 2 diabetes (HR [95% CI] per 1 SD difference: 0·79 [0·73-0·85] for pentadecanoic acid and 0·67 [0·63-0·71] for heptadecanoic acid), as were measured longer-chain SFAs (20:0 [arachidic acid], 22:0 [behenic acid], 23:0 [tricosanoic acid], and 24:0 [lignoceric acid]), with HRs ranging from 0·72 to 0·81 (95% CIs ranging between 0·61 and 0·92). Our findings were robust to a range of sensitivity analyses. Interpretation: Different individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions, which suggests that SFAs are not homogeneous in their effects. Our findings emphasise the importance of the recognition of subtypes of these fatty acids. An improved understanding of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed.
UR - http://www.scopus.com/inward/record.url?scp=84922235687&partnerID=8YFLogxK
U2 - 10.1016/S2213-8587(14)70146-9
DO - 10.1016/S2213-8587(14)70146-9
M3 - Article
C2 - 25107467
AN - SCOPUS:84922235687
SN - 2213-8587
VL - 2
SP - 810
EP - 818
JO - The Lancet Diabetes and Endocrinology
JF - The Lancet Diabetes and Endocrinology
IS - 10
ER -