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.
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.


METHODS
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.


CONCLUSIONS
The FA profile of erythrocyte membrane phospholipids and activity of desaturase enzymes are strongly linked to the incidence of type 2 diabetes.
Kröger
Janine
J
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. kroeger@dife.de
Zietemann
Vera
V
Enzenbach
Cornelia
C
Weikert
Cornelia
C
Jansen
Eugène Hjm
EH
Döring
Frank
F
Joost
Hans-Georg
HG
Boeing
Heiner
H
Schulze
Matthias B
MB
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D000090943:Delta-5 Fatty Acid Desaturase; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D004041:Dietary Fats / Q000008:administration & dosage*; D004910:Erythrocyte Membrane / Q000737:chemistry*; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D010743:Phospholipids / Q000097:blood*; D011446:Prospective Studies; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism
D000090943:Delta-5 Fatty Acid Desaturase; D004041:Dietary Fats; D005227:Fatty Acids; D010743:Phospholipids; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; C000716847:FADS1 protein, human; C533241:FADS2 protein, human