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Randomized Controlled Trial
. 2014 Oct;2(10):810-8.
doi: 10.1016/S2213-8587(14)70146-9. Epub 2014 Aug 5.

Differences in the Prospective Association Between Individual Plasma Phospholipid Saturated Fatty Acids and Incident Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study

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Free PMC article
Randomized Controlled Trial

Differences in the Prospective Association Between Individual Plasma Phospholipid Saturated Fatty Acids and Incident Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study

Nita G Forouhi et al. Lancet Diabetes Endocrinol. .
Free PMC article

Abstract

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.

Funding: EU FP6 programme, Medical Research Council Epidemiology Unit, Medical Research Council Human Nutrition Research, and Cambridge Lipidomics Biomarker Research Initiative.

Figures

Figure 1
Figure 1
Case-cohort design of the InterAct study and the number of participants included in this analysis * A random sample of 2055 type 2 diabetes cases from Denmark was included after the exclusion of 2577 cases.
Figure 2
Figure 2
Hazard ratios and 95% CIs for associations between plasma phospholipid saturated fatty acids and incident type 2 diabetes Associations per 1 SD difference in (A) even-chain fatty acids (saturated fatty acid [SFA] group 1: the sum of 14:0, 16:0, and 18:0), (B) odd-chain fatty acids (SFA group 2: the sum of 15:0 and 17:0), and (C) long- and very-long-chain fatty acids (SFA group 3: the sum of 20:0, 22:0, 23:0, and 24:0) and type 2 diabetes. Estimates are per country and the pooled estimate is based on random-effects meta-analysis. The analyses included 12 132 cases of type 2 diabetes and 15 919 people in the subcohort (including 755 individuals with type 2 diabetes in the subcohort); used age as the underlying time variable; and were adjusted for centre, sex, smoking status, alcohol intake, physical activity, education level, total energy intake, and BMI.
Figure 3
Figure 3
Adjusted Pearson correlation coefficients for the correlation between plasma phospholipid saturated fatty acids (mol%) and types of self-reported food intake (g/day) in the subcohort (n=15 919) Correlations for (A) even-chain fatty acids (saturated fatty acid [SFA] group 1: the sum of 14:0, 16:0 and 18:0), (B) odd-chain fatty acids (SFA group 2: the sum of 15:0 and 17:0), and (C) long- and very-long-chain fatty acids (SFA group 3: the sum of 20:0, 22:0, 23:0 and 24:0). Correlations are adjusted for age, sex, BMI, and total energy intake. Error bars are 95% CIs.

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