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Elhadad, M.A. ; Jonasson, C.* ; Huth, C. ; Wilson, R. ; Gieger, C. ; Matias-Garcia, P.R. ; Grallert, H. ; Graumann, J.* ; Gailus-Durner, V. ; Rathmann, W.* ; von Toerne, C. ; Hauck, S.M. ; Koenig, W.* ; Sinner, M.F.* ; Oprea, T.I.* ; Suhre, K.* ; Thorand, B. ; Hveem, K.* ; Peters, A. ; Waldenberger, M.

Deciphering the plasma proteome of type 2 diabetes.

Diabetes 69, 2766-2778 (2020)
Publ. Version/Full Text Postprint DOI PMC
Open Access Green
With an estimated prevalence of 463 million affected, type 2 diabetes represents a major challenge to health care systems worldwide. Analyzing the plasma proteomes of individuals with type 2 diabetes may illuminate hitherto unknown functional mechanisms underlying disease pathology. We assessed the associations between type 2 diabetes and >1,000 plasma proteins in the Cooperative Health Research in the Region of Augsburg (KORA) F4 cohort (n = 993, 110 cases), with subsequent replication in the third wave of the Nord-Trøndelag Health Study (HUNT3) cohort (n = 940, 149 cases). We computed logistic regression models adjusted for age, sex, BMI, smoking status, and hypertension. Addition-ally, we investigated associations with incident type 2 diabetes and performed two-sample bidirectional Mendelian randomization (MR) analysis to prioritize our results. Association analysis of prevalent type 2 diabetes revealed 24 replicated proteins, of which 8 are novel. Proteins showing association with incident type 2 diabetes were aminoacylase-1, growth hormone receptor, and insulin-like growth factor–binding protein 2. Aminoacylase-1 was associated with both prevalent and incident type 2 diabetes. MR analysis yielded nominally significant causal effects of type 2 diabetes on cathepsin Z and rennin, both known to have roles in the pathophysiological pathways of cardiovascular disease, and of sex hormone–binding globulin on type 2 diabetes. In conclusion, our high-throughput pro-teomics study replicated previously reported type 2 diabetes–protein associations and identified new candidate proteins possibly involved in the pathogenesis of type 2 diabetes.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Mendelian Randomization; Insulin-resistance; Biomarkers; Proteins; Risk; Metabolism; Variants; Mellitus; Hormone; Kora
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 69, Issue: 12, Pages: 2766-2778 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Experimental Genetics (IEG)
CF Metabolomics & Proteomics (CF-MPC)
Grants Qatar National Research Fund
State of Bavaria
Deutsche Forschungsgemeinschaft
Bundesministerium für Bildung und Forschung
Biomedical Research Program at Weill Cornell Medicine in Qatar - Qatar Foundation
Norwegian Ministry of Health
Norges Teknisk-Naturvitenskapelige Universitet
Norges Forskningsrad
Helse Midt-Norge
Nord-Trondelag County Council
Norwegian Institute of Public Health
Deutsches Zentrum für Herz-Kreislaufforschung
National Institutes of Health
Helmholtz Zentrum Munchen -German Research Center for Environmental Health - German Federal Ministry of Education and Research