Journal
CARDIOVASCULAR DIABETOLOGY
Volume 21, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12933-022-01513-9
Keywords
Adrenomedullin; C-terminal-proendothelin-1; Endothelin-1; Epidemiology; Incident type 2 diabetes; Mendelian randomisation; Mid-regional-proadrenomedullin; Cohort study
Funding
- Projekt DEAL
- European Union Seventh Framework Programme (FP7/2007-2013) [HEALTH-F2-2011-278913]
- EU [BMH4-CT98-3183, QLG2-CT-2002-01254]
- European Network for Genetic and Genomic Epidemiology (ENGAGE) (FP7) [HEALTH-F4-2007-201413]
- Consortium on Health and Ageing: Network of cohorts in Europe and the United States (CHANCES) (FP7), euCanSHare (Horizon 2020) [HEALTH-F3-2010-242244, 825903]
- Digital, Risk-based Screening for Atrial Fibrillation in the European Community project-European Union (AFFECT-EU) (Horizon 2020) [847770]
- Medical Research Council, London [G0601463, 80983]
- Helmholtz Zentrum Munchen -German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)
- State of Bavaria
- Virtual Institute of Diabetes Research (Helmholtz Zentrum Munchen)
- Ludwig-MaximiliansUniversitat Munchen
- Helmholtz Zentrum Munchen
- German Diabetes Center (DDZ)
- Federal Ministry of Health (Berlin, Germany)
- Ministry of Culture and Science of the state North Rhine Westphalia (Dusseldorf, Germany)
- German Research Foundation (DFG) [RA-45,913/3-1]
- Finnish Institute for Health and Welfare
- Academy of Finland
- Health and Social Care (HSC) Research and Development Office of the Northern Ireland Public Health Agency
- UK Prevention Research Partnership (UKPRP)
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The study found that higher concentrations of CT-proET-1 and MR-proADM are associated with incident type 2 diabetes, especially in obese individuals. Mendelian randomisation analysis suggests a probable causal link for CT-proET-1.
Background Endothelin-1 (ET-1) and adrenomedullin (ADM) are commonly known as vasoactive peptides that regulate vascular homeostasis. Less recognised is the fact that both peptides could affect glucose metabolism. Here, we investigated whether ET-1 and ADM, measured as C-terminal-proET-1 (CT-proET-1) and mid-regional-proADM (MR-proADM), respectively, were associated with incident type 2 diabetes. Methods Based on the population-based Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium data, we performed a prospective cohort study to examine associations of CT-proET-1 and MR-proADM with incident type 2 diabetes in 12,006 participants. During a median follow-up time of 13.8 years, 862 participants developed type 2 diabetes. The associations were examined in Cox proportional hazard models. Additionally, we performed two-sample Mendelian randomisation analyses using published data. Results CT-proET-1 and MR-proADM were positively associated with incident type 2 diabetes. The multivariable hazard ratios (HRs) [95% confidence intervals (CI)] were 1.10 [1.03; 1.18], P = 0.008 per 1-SD increase of CT-proET-1 and 1.11 [1.02; 1.21], P = 0.016 per 1-SD increase of log MR-proADM, respectively. We observed a stronger association of MR-proADM with incident type 2 diabetes in obese than in non-obese individuals (P-interaction with BMI < 0.001). The HRs [95%CIs] were 1.19 [1.05; 1.34], P = 0.005 and 1.02 [0.90; 1.15], P = 0.741 in obese and non-obese individuals, respectively. Our Mendelian randomisation analyses yielded a significant association of CT-proET-1, but not of MR-proADM with type 2 diabetes risk. Conclusions Higher concentrations of CT-proET-1 and MR-proADM are associated with incident type 2 diabetes, but our Mendelian randomisation analysis suggests a probable causal link for CT-proET-1 only. The association of MR-proADM seems to be modified by body composition.
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