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Published in: Diabetologia 2/2015

Open Access 01-02-2015 | Article

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

Authors: Janine Kröger, Simone Jacobs, Eugène H. J. M. Jansen, Andreas Fritsche, Heiner Boeing, Matthias B. Schulze

Published in: Diabetologia | Issue 2/2015

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Abstract

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.
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Literature
1.
go back to reference Hodge AM, English DR, O'Dea K et al (2007) Plasma phospholipid and dietary fatty acids as predictors of type 2 diabetes: interpreting the role of linoleic acid. Am J Clin Nutr 86:189–197PubMed Hodge AM, English DR, O'Dea K et al (2007) Plasma phospholipid and dietary fatty acids as predictors of type 2 diabetes: interpreting the role of linoleic acid. Am J Clin Nutr 86:189–197PubMed
2.
go back to reference Krachler B, Norberg M, Eriksson JW et al (2008) Fatty acid profile of the erythrocyte membrane preceding development of type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis 18:503–510PubMedCrossRef Krachler B, Norberg M, Eriksson JW et al (2008) Fatty acid profile of the erythrocyte membrane preceding development of type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis 18:503–510PubMedCrossRef
3.
go back to reference Kroger J, Zietemann V, Enzenbach C et al (2011) Erythrocyte membrane phospholipid fatty acids, desaturase activity, and dietary fatty acids in relation to risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Am J Clin Nutr 93:127–142PubMedCrossRef Kroger J, Zietemann V, Enzenbach C et al (2011) Erythrocyte membrane phospholipid fatty acids, desaturase activity, and dietary fatty acids in relation to risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Am J Clin Nutr 93:127–142PubMedCrossRef
4.
go back to reference Patel PS, Sharp SJ, Jansen E et al (2010) Fatty acids measured in plasma and erythrocyte-membrane phospholipids and derived by food-frequency questionnaire and the risk of new-onset type 2 diabetes: a pilot study in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. Am J Clin Nutr 92:1214–1222PubMedCrossRef Patel PS, Sharp SJ, Jansen E et al (2010) Fatty acids measured in plasma and erythrocyte-membrane phospholipids and derived by food-frequency questionnaire and the risk of new-onset type 2 diabetes: a pilot study in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. Am J Clin Nutr 92:1214–1222PubMedCrossRef
5.
go back to reference Wang L, Folsom AR, Zheng ZJ, Pankow JS, Eckfeldt JH, Investigators AS (2003) Plasma fatty acid composition and incidence of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr 78:91–98PubMed Wang L, Folsom AR, Zheng ZJ, Pankow JS, Eckfeldt JH, Investigators AS (2003) Plasma fatty acid composition and incidence of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr 78:91–98PubMed
6.
go back to reference Mahendran Y, Agren J, Uusitupa M et al (2014) Association of erythrocyte membrane fatty acids with changes in glycemia and risk of type 2 diabetes. Am J Clin Nutr 99:79–85PubMedCrossRef Mahendran Y, Agren J, Uusitupa M et al (2014) Association of erythrocyte membrane fatty acids with changes in glycemia and risk of type 2 diabetes. Am J Clin Nutr 99:79–85PubMedCrossRef
8.
go back to reference Ginsberg BH, Brown TJ, Simon I, Spector AA (1981) Effect of the membrane lipid environment on the properties of insulin receptors. Diabetes 30:773–780PubMedCrossRef Ginsberg BH, Brown TJ, Simon I, Spector AA (1981) Effect of the membrane lipid environment on the properties of insulin receptors. Diabetes 30:773–780PubMedCrossRef
9.
go back to reference Pilch PF, Thompson PA, Czech MP (1980) Coordinate modulation of D-glucose transport activity and bilayer fluidity in plasma membranes derived from control and insulin-treated adipocytes. Proc Natl Acad Sci U S A 77:915–918PubMedCentralPubMedCrossRef Pilch PF, Thompson PA, Czech MP (1980) Coordinate modulation of D-glucose transport activity and bilayer fluidity in plasma membranes derived from control and insulin-treated adipocytes. Proc Natl Acad Sci U S A 77:915–918PubMedCentralPubMedCrossRef
10.
go back to reference Vazquez CM, Rovira N, Ruiz-Gutierrez V, Planas JM (1997) Developmental changes in glucose transport, lipid composition, and fluidity of jejunal BBM. Am J Physiol 273:R1086–R1093PubMed Vazquez CM, Rovira N, Ruiz-Gutierrez V, Planas JM (1997) Developmental changes in glucose transport, lipid composition, and fluidity of jejunal BBM. Am J Physiol 273:R1086–R1093PubMed
11.
go back to reference Wu H, Ding EL, Toledo ET et al (2013) A novel fatty acid lipophilic index and risk of CHD in US men: the health professionals follow-up study. Br J Nutr 110:466–474PubMedCentralPubMedCrossRef Wu H, Ding EL, Toledo ET et al (2013) A novel fatty acid lipophilic index and risk of CHD in US men: the health professionals follow-up study. Br J Nutr 110:466–474PubMedCentralPubMedCrossRef
12.
go back to reference Toledo E, Campos H, Ding EL et al (2013) A novel fatty acid profile index—the lipophilic index—and risk of myocardial infarction. Am J Epidemiol 178:392–400PubMedCentralPubMedCrossRef Toledo E, Campos H, Ding EL et al (2013) A novel fatty acid profile index—the lipophilic index—and risk of myocardial infarction. Am J Epidemiol 178:392–400PubMedCentralPubMedCrossRef
13.
go back to reference Boeing H, Korfmann A, Bergmann MM (1999) Recruitment procedures of EPIC-Germany. European Investigation into Cancer and Nutrition. Ann Nutr Metab 43:205–215PubMedCrossRef Boeing H, Korfmann A, Bergmann MM (1999) Recruitment procedures of EPIC-Germany. European Investigation into Cancer and Nutrition. Ann Nutr Metab 43:205–215PubMedCrossRef
14.
go back to reference Barlow WE, Ichikawa L, Rosner D, Izumi S (1999) Analysis of case-cohort designs. J Clin Epidemiol 52:1165–1172PubMedCrossRef Barlow WE, Ichikawa L, Rosner D, Izumi S (1999) Analysis of case-cohort designs. J Clin Epidemiol 52:1165–1172PubMedCrossRef
15.
go back to reference Saldanha C, Sargento L, Monteiro J, Perdigao C, Ribeiro C, Martins-Silva J (1999) Impairment of the erythrocyte membrane fluidity in survivors of acute myocardial infarction. A prospective study. Clin Hemorheol Microcirc 20:111–116PubMed Saldanha C, Sargento L, Monteiro J, Perdigao C, Ribeiro C, Martins-Silva J (1999) Impairment of the erythrocyte membrane fluidity in survivors of acute myocardial infarction. A prospective study. Clin Hemorheol Microcirc 20:111–116PubMed
17.
go back to reference Jacobs S, Kroger J, Floegel A et al (2014) Evaluation of various biomarkers as potential mediators of the association between coffee consumption and incident type 2 diabetes in the EPIC-Potsdam Study. Am J Clin Nutr 100:891–900PubMedCrossRef Jacobs S, Kroger J, Floegel A et al (2014) Evaluation of various biomarkers as potential mediators of the association between coffee consumption and incident type 2 diabetes in the EPIC-Potsdam Study. Am J Clin Nutr 100:891–900PubMedCrossRef
18.
go back to reference Prentice RL (1986) A case-cohort design for epidemiologic cohort studies and disease prevention trials. Biometrika 73:1–11CrossRef Prentice RL (1986) A case-cohort design for epidemiologic cohort studies and disease prevention trials. Biometrika 73:1–11CrossRef
19.
go back to reference Willett WC, Howe GR, Kushi LH (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65:1220S–1228S, discussion 1229S-1231SPubMed Willett WC, Howe GR, Kushi LH (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65:1220S–1228S, discussion 1229S-1231SPubMed
20.
go back to reference Zicha J, Kunes J, Devynck MA (1999) Abnormalities of membrane function and lipid metabolism in hypertension: a review. Am J Hypertens 12:315–331PubMedCrossRef Zicha J, Kunes J, Devynck MA (1999) Abnormalities of membrane function and lipid metabolism in hypertension: a review. Am J Hypertens 12:315–331PubMedCrossRef
21.
go back to reference Hirata F, Axelrod J (1978) Enzymatic methylation of phosphatidylethanolamine increases erythrocyte membrane fluidity. Nature 275:219–220PubMedCrossRef Hirata F, Axelrod J (1978) Enzymatic methylation of phosphatidylethanolamine increases erythrocyte membrane fluidity. Nature 275:219–220PubMedCrossRef
22.
go back to reference Madden TD, Chapman D, Quinn PJ (1979) Cholesterol modulates activity of calcium-dependent ATPase of the sarcoplasmic reticulum. Nature 279:538–541PubMedCrossRef Madden TD, Chapman D, Quinn PJ (1979) Cholesterol modulates activity of calcium-dependent ATPase of the sarcoplasmic reticulum. Nature 279:538–541PubMedCrossRef
23.
go back to reference Puskin JS, Martin T (1979) Divalent cation binding to phospholipid vesicles. Dependence on temperature and lipid fluidity. Biochim Biophys Acta 552:53–65PubMedCrossRef Puskin JS, Martin T (1979) Divalent cation binding to phospholipid vesicles. Dependence on temperature and lipid fluidity. Biochim Biophys Acta 552:53–65PubMedCrossRef
24.
go back to reference Greenland S (1998) Basic methods for sensitivity analysis and external adjustment. In: Rothmann JR, Greenland S (eds) Modern epidemiology. Lippincott-Raven, Philadelphia Greenland S (1998) Basic methods for sensitivity analysis and external adjustment. In: Rothmann JR, Greenland S (eds) Modern epidemiology. Lippincott-Raven, Philadelphia
Metadata
Title
Erythrocyte membrane fatty acid fluidity and risk of type 2 diabetes in the EPIC-Potsdam study
Authors
Janine Kröger
Simone Jacobs
Eugène H. J. M. Jansen
Andreas Fritsche
Heiner Boeing
Matthias B. Schulze
Publication date
01-02-2015
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 2/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-014-3421-7

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