Abstract
Aims/hypothesisThe fluidity of cell membranes has been hypothesised as an important link in the association of fatty acids (FAs) with diabetes risk. The lipophilic index, which can be derived from the FA profile of blood or tissues, has recently been proposed as a novel measure of cell membrane FA fluidity. In this study we aimed to evaluate the lipophilic index in relation to the incidence of type 2 diabetes.MethodsWe applied a nested case-cohort design (n = 1,740, including 362 cases) within the EPIC-Potsdam study, which involves 27,548 middle-aged men and women. Erythrocyte membrane FA proportions were measured at baseline and physician-confirmed incident diabetes was assessed during a mean follow-up of 7.0 years. The lipophilic index was calculated as the sum of the products of the FA proportions with the respective FA melting points.ResultsAfter multivariable adjustments, including body size measures, there was a positive association between the lipophilic index and diabetes risk (HR comparing top with bottom quartile 1.59 (95% CI 1.08, 2.34), p for trend across quartiles = 0.005). Adjustment for FAs, which are considered established diabetes risk markers, did not substantially attenuate this association.Conclusions/interpretationA high lipophilic index, reflecting lower membrane fluidity, may be associated with a higher risk of type 2 diabetes. Our data corroborate the hypothesis that membrane fluidity may be an important mediator that links intake and metabolism of FAs to diabetes risk.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-014-3421-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Highlights
The fatty acid (FA) profile of blood and tissues integrates the complex interplay between dietary intake of fatty acids (FAs) and endogenous FA metabolism, and has been shown to be associated with risk of type 2 diabetes in a number of studies [1,2,3,4,5,6]
We aimed to investigate prospectively the lipophilic index as a measure of the FA fluidity of erythrocyte membranes in relation to the incidence of type 2 diabetes
We investigated whether excluding participants in the unfasted state at blood collection affects the association between the lipophilic index and triacylglycerol levels (n=1,029)
Summary
The fatty acid (FA) profile of blood and tissues integrates the complex interplay between dietary intake of FAs and endogenous FA metabolism, and has been shown to be associated with risk of type 2 diabetes in a number of studies [1,2,3,4,5,6]. There is a long-held view that the fluidity of the cell membrane, which is importantly determined by its FA composition, affects cellular functions [7]. Despite this notion of an important role of membrane fluidity for diabetes development, there is scarce data to support the relevance of this hypothesis. Membrane fluidity is strongly determined by the van der Waals forces between FAs in the phospholipid bilayers. Long-chain saturated FAs (SFAs) with a straight FA chain are characterised by a relatively high melting point, whereas polyunsaturated fatty acids (PUFAs) with a high number of double bonds, leading to a complex three-dimensional structure, generally have lower melting points
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