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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
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
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.
Reviewing status Peer reviewed
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