Nita G Forouhi , Dr, FFPHM a , * , Albert Koulman , PhD b , Stephen J Sharp , MSc a , Fumiaki Imamura , PhD a , Janine Kröger , DrPH c , Matthias B Schulze , Prof, DrPH c , Francesca L Crowe , PhD d , José María Huerta , PhD e , f , Marcela Guevara , MD f , g , Joline WJ Beulens , PhD h , Geertruida J van Woudenbergh , PhD i , Laura Wang , PhD b , Keith Summerhill , BSc b , Julian L Griffin , DPhil b , Edith JM Feskens , Prof, PhD i , Pilar Amiano , MSc f , j , k , Heiner Boeing , Prof, PhD c , Françoise Clavel-Chapelon , PhD l , m , n , Laureen Dartois , MSc l , m , n , Guy Fagherazzi , PhD l , m , n , Paul W Franks , Prof, PhD o , p , Carlos Gonzalez , PhD q , Marianne Uhre Jakobsen , PhD r , Rudolf Kaaks , Prof, PhD s , Timothy J Key , Prof, DPhil d , Kay-Tee Khaw , Prof, FRCP t , Tilman Kühn , PhD s , Amalia Mattiello , PhD u , Peter M Nilsson , Prof, PhD o , Kim Overvad , Prof, PhD r , v , Valeria Pala , PhD w , Domenico Palli , MD x , J Ramón Quirós , MD y , Olov Rolandsson , PhD p , Nina Roswall , PhD z , Carlotta Sacerdote , PhD aa , ab , María-José Sánchez , PhD f , ac , ad , Nadia Slimani , PhD ae , Annemieke MW Spijkerman , PhD af , Anne Tjonneland , Prof, DrMedSci ag , Maria-José Tormo , PhD e , f , ah , Rosario Tumino , MD ai , aj , Daphne L van der A , PhD af , Yvonne T van der Schouw , Prof, PhD h , Claudia Langenberg , PhD a , Elio Riboli , Prof, ScM ak , Nicholas J Wareham , Prof, FRCP a
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.
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.
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.
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.