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
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Background The long-term role of fatty acids (FAs) in the cause of diabetes remains largely unclear.Objective We aimed to investigate erythrocyte membrane FAs, desaturase activity, and dietary FAs in relation to the incidence of type 2 diabetes.Design We applied a nested case-cohort design (n = 2724, including 673 incident diabetes cases) within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study, which involves 27,548 middle-aged subjects. Thirty erythrocyte membrane FAs (percentage of total FAs) and FA intake (percentage of total fat) were measured at baseline, and physician-confirmed incident diabetes was assessed during a mean follow-up of 7.0 y. We evaluated Δ⁵ desaturase (D5D) and Δ⁶ desaturase (D6D) activity by using FA product-to-precursor ratios (traditional approach) and by investigating variants in FADS1 and FADS2 genes that encode these desaturases (Mendelian randomization approach).Results As a main finding, erythrocyte 16:1n-7 and 18:3n-6 and FA ratios, which reflect stearoyl coenzyme A desaturase (SCD) and D6D activity, were directly related to diabetes risk in multivariable-adjusted models [relative risks (95% CIs) comparing extreme quintiles: 16:1n-7, 2.11 (1.46, 3.05); 18:3n-6, 2.00 (1.38, 2.88); SCD, 2.61 (1.75, 3.89); and D6D, 2.46 (1.67, 3.63)], whereas the FA ratio that reflects D5D activity was inversely associated with risk [0.46 (0.31, 0.70)]. The Mendelian randomization approach corroborated the direct relation for D6D activity and tended to support the inverse relation for D5D activity. Proportions of dietary FAs showed only modest to low correlations with erythrocyte FAs and were not significantly associated with risk.Conclusion The FA profile of erythrocyte membrane phospholipids and activity of desaturase enzymes are strongly linked to the incidence of type 2 diabetes.
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Endogenous fatty acid composition in several lipid compartments has been related to the risk of type 2 diabetes in several prospective cohorts, including EPIC-Potsdam.
“Consistently, endogenous FA composition in several lipid compartments has been related to the risk of type 2 diabetes in several prospective cohorts, including EPIC-Potsdam (36).”
From Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes (2015) · cites this paper as [36]
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References 68 · Cited by 270
- Authors
- Kröger, J., Zietemann, V., Enzenbach, C., Weikert, C., Jansen, E. H., Döring, F., Joost, H.-G., Boeing, H., & Schulze, M. B.
- Affiliations
- Christian-Albrechts-Universität zu Kiel (DE)
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 93
- Issue
- 1
- Pages
- 127-142
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2108306062
- Cited by
- 270
- References
- 68
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 7 · 2023: 8 · 2022: 16 · 2021: 10 · 2020: 22 · 2019: 22 · 2018: 23 · 2017: 14 · 2016: 35 · 2015: 21 · 2014: 24 · 2013: 23 · 2012: 15
- FWCI
- 13.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Rivm Repository (Netherlands National Institute for Public Health and the Environment) (submittedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- erythrocyte membrane fatty acids, fatty acid desaturase activity, stearoyl-CoA desaturase, delta-6 desaturase, delta-5 desaturase, dietary fatty acids, FADS1, FADS2, omega-3 fatty acids, omega-6 fatty acids
- MeSH terms
- Delta-5 Fatty Acid Desaturase, Adult, Aged, Diabetes Mellitus, Type 2, Dietary Fats, Erythrocyte Membrane, Fatty Acids, Female, Genotype, Humans, Male, Middle Aged, Phospholipids, Prospective Studies, Stearoyl-CoA Desaturase, Case-Control Studies, Fatty Acid Desaturases, Mendelian Randomization Analysis
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