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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)
Verlagsversion 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Mendelian Randomization; Insulin-resistance; Biomarkers; Proteins; Risk; Metabolism; Variants; Mellitus; Hormone; Kora
Sprache englisch
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Zeitschrift Diabetes
Quellenangaben Band: 69, Heft: 12, Seiten: 2766-2778 Artikelnummer: , Supplement: ,
Verlag American Diabetes Association
Verlagsort Alexandria, VA.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Experimental Genetics (IEG)
CF Metabolomics & Proteomics (CF-MPC)
POF Topic(s) 30202 - Environmental Health
30201 - Metabolic Health
30203 - Molecular Targets and Therapies
90000 - German Center for Diabetes Research
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) G-504091-001
G-504090-001
G-504000-006
G-504091-004
G-504091-002
G-500600-001
G-505700-001
G-504000-002
G-504000-010
G-501900-401
Förderungen 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
DOI 10.2337/db20-0296
WOS ID WOS:000594819600022
Scopus ID 85096609099
PubMed ID 32928870
Erfassungsdatum 2020-10-14
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