American Diabetes Association
Sujana_etal_2021_OnlineOnly_SupplementalMaterials_R2.pdf (518.08 kB)

Natriuretic peptides and risk of type 2 diabetes: Results from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium

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posted on 2021-09-14, 16:36 authored by Chaterina Sujana, Veikko Salomaa, Frank Kee, Simona Costanzo, Stefan Söderberg, Jens Jordan, Pekka Jousilahti, Charlotte Neville, Licia Iacoviello, Viktor Oskarsson, Dirk Westermann, Wolfgang Koenig, Kari Kuulasmaa, Jaakko Reinikainen, Stefan Blankenberg, Tanja Zeller, Christian Herder, Ulrich Mansmann, Annette Peters, Barbara Thorand, the BiomarCaRE Consortium

Objective: Natriuretic peptide (NP) concentrations are increased in cardiovascular diseases (CVD) but are associated with a lower diabetes risk. We investigated associations of N-terminal pro-B-type NP (NT-proBNP) and mid-regional pro-atrial NP (MR-proANP) with incident type 2 diabetes stratified by the presence of CVD.

Research Design and Methods: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe-(BiomarCaRE) Consortium, we included 45,477 participants with NT-proBNP measurements (1,707 developed type 2 diabetes over 6.5 years of median follow-up; among these, 209 had CVD at baseline) and 11,537 participants with MR-proANP measurements (857 developed type 2 diabetes over 13.8 years of median follow-up; among these, 106 had CVD at baseline). The associations were estimated using multivariable Cox regression models.

Results: Both NPs were inversely associated with incident type 2 diabetes (hazard ratios [95%CI] per 1-standard deviation increase of log NP: 0.84 [0.79; 0.89] for NT-proBNP and 0.77 [0.71; 0.83] for MR-proANP). The inverse association between NT-proBNP and type 2 diabetes was significant in individuals without, but not in individuals with CVD (0.81 [0.76; 0.86] vs 1.04 [0.90; 1.19]; P-multiplicative interaction= 0.001). There was no significant difference in the association of MR-proANP with type 2 diabetes between individuals without and with CVD (0.75 [0.69; 0.82] vs 0.81 [0.66; 0.99]; P-multiplicative interaction= 0.236).

Conclusions: NT-proBNP and MR-proANP are inversely associated with incident type 2 diabetes. However, the inverse association of NT-proBNP seems to be modified by the presence of CVD. Further investigations are warranted to confirm our findings and to investigate the underlying mechanisms.


The BiomarCaRE Project is funded by the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement No. HEALTH-F2-2011–278913. The MORGAM Project has received funding also from EU projects MORGAM (Biomed, BMH4-CT98-3183), GenomEUtwin (FP5, QLG2-CT-2002-01254), ENGAGE (FP7, HEALTH-F4-2007-201413), CHANCES (FP7, HEALTH-F3-2010-242244), euCanSHare (Horizon 2020, No. 825903) and AFFECT-EU (Horizon 2020, No. 847770); and Medical Research Council, London (G0601463, No. 80983: Biomarkers in the MORGAM Populations). This has supported central coordination, workshops and part of the activities of the MORGAM Data Centre, the MORGAM Laboratories and the MORGAM Participating Centres. The current study was partly funded by the Helmholtz Alliance ‘Aging and Metabolic Programming, AMPro’. VS was supported by the Finnish Foundation for Cardiovascular Research. The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. The KORA study was supported by a research grant from the Virtual Institute of Diabetes Research (Helmholtz Zentrum München), the Clinical Cooperation Group Diabetes between Ludwig-Maximilians-Universität München and Helmholtz Zentrum München, and by the German Diabetes Center (DDZ). The German Diabetes Center was supported by the Federal Ministry of Health (Berlin, Germany) and the Ministry of Culture and Science of the state North Rhine Westphalia (Düsseldorf, Germany). The KORA F4 study was partly funded by a grant from the German Research Foundation (DFG) (RA-45,913/3-1). The FINRISK surveys have funded mainly from budgetary funds of the Finnish Institute for Health and Welfare. Additional supplementary funding has been obtained from several domestic foundations and from the Academy of Finland. The PRIME Belfast was previously supported through grants fr