Erythrocyte membrane fatty acid fluidity and risk of type 2 diabetes in the EPIC-Potsdam study

AIMS/HYPOTHESIS: The 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. METHODS: We 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. RESULTS: After 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/INTERPRETATION: A 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 MATERIAL: The 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.