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Wittenbecher, C.* ; Mühlenbruch, K.* ; Kröger, J.* ; Jacobs, S.* ; Kuxhaus, O.* ; Floegel, A.* ; Fritsche, A.* ; Pischon, T.* ; Prehn, C. ; Adamski, J. ; Joost, H.-G.* ; Boeing, H.* ; Schulze, M.B.*

Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes.

Am. J. Clin. Nutr. 101, 1241-1250 (2015)
Publ. Version/Full Text DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
BACKGROUND: Habitual red meat consumption was consistently related to a higher risk of type 2 diabetes in observational studies. Potentially underlying mechanisms are unclear. OBJECTIVE: This study aimed to identify blood metabolites that possibly relate red meat consumption to the occurrence of type 2 diabetes. DESIGN: Analyses were conducted in the prospective European Prospective Investigation into Cancer and Nutrition-Potsdam cohort (n = 27,548), applying a nested case-cohort design (n = 2681, including 688 incident diabetes cases). Habitual diet was assessed with validated semiquantitative food-frequency questionnaires. Total red meat consumption was defined as energy-standardized summed intake of unprocessed and processed red meats. Concentrations of 14 amino acids, 17 acylcarnitines, 81 glycerophospholipids, 14 sphingomyelins, and ferritin were determined in serum samples from baseline. These biomarkers were considered potential mediators of the relation between total red meat consumption and diabetes risk in Cox models. The proportion of diabetes risk explainable by biomarker adjustment was estimated in a bootstrapping procedure with 1000 replicates. RESULTS: After adjustment for age, sex, lifestyle, diet, and body mass index, total red meat consumption was directly related to diabetes risk [HR for 2 SD (11 g/MJ): 1.26; 95% CI: 1.01, 1.57]. Six biomarkers (ferritin, glycine, diacyl phosphatidylcholines 36:4 and 38:4, lysophosphatidylcholine 17:0, and hydroxy-sphingomyelin 14:1) were associated with red meat consumption and diabetes risk. The red meat-associated diabetes risk was significantly (P < 0.001) attenuated after simultaneous adjustment for these biomarkers [biomarker-adjusted HR for 2 SD (11 g/MJ): 1.09; 95% CI: 0.86, 1.38]. The proportion of diabetes risk explainable by respective biomarkers was 69% (IQR: 49%, 106%). CONCLUSION: In our study, high ferritin, low glycine, and altered hepatic-derived lipid concentrations in the circulation were associated with total red meat consumption and, independent of red meat, with diabetes risk. The red meat-associated diabetes risk was largely attenuated after adjustment for selected biomarkers, which is consistent with the presumed mediation hypothesis.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Biomarkers ; Cohort Study ; Metabolomics ; Red Meat ; Type 2 Diabetes Mellitus; Nutrition (epic)-potsdam; Glycine Metabolism; Prevention Trials; Epic-germany; Iron Stores; Risk; Cancer; Diet; Food; Identification
ISSN (print) / ISBN 0002-9165
e-ISSN 1938-3207
Journal American Journal of Clinical Nutrition
Quellenangaben Volume: 101, Issue: 6, Pages: 1241-1250 Article Number: , Supplement: ,
Publisher American Society for Nutrition
Publishing Place Bethesda
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Experimental Genetics (IEG)
Institute of Diabetes Research and Metabolic Diseases (IDM)