Associations of the vasoactive peptides CT-proET-1 and MR-proADM with incident type 2 diabetes: results from the BiomarCaRE Consortium.

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. 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. 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. 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.

Sujana C ，Salomaa V ，Kee F ，Seissler J ，Jousilahti P ，Neville C ，Then C ，Koenig W ，Kuulasmaa K ，Reinikainen J ，Blankenberg S ，Zeller T ，Herder C ，Mansmann U ，Peters A ，Thorand B ，BiomarCaRE Consortium ... -  《Cardiovascular Diabetology》

Associations of cardiac stress biomarkers with incident type 2 diabetes and changes in glucose metabolism: KORA F4/FF4 study.

Sujana C ，Seissler J ，Jordan J ，Rathmann W ，Koenig W ，Roden M ，Mansmann U ，Herder C ，Peters A ，Thorand B ，Then C ... -  《Cardiovascular Diabetology》

Endothelium-associated biomarkers mid-regional proadrenomedullin and C-terminal proendothelin-1 have good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia: A prospective cohort study.

We assessed the ability of mid-regional proadrenomedullin (MR-proADM) and C-terminal proendothelin-1 (CT-proET-1) to predict 28-day mortality in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Biomarkers were collected during the first seven days in this prospective observational cohort study. We investigated the relationship between biomarkers and mortality in a multivariable Cox regression model adjusted for age and SOFA score. In 105 critically ill patients with confirmed SARS-CoV-2 pneumonia 28-day mortality was 28.6%. MR-proADM and CT-proET-1 were significantly higher in 28-day non-survivors at baseline and over time. ROC curves revealed high accuracy to identify non-survivors for baseline MR-proADM and CT-proET-1, AUC 0.84, (95% CI 0.76-0.92), p < 0.001 and 0.79, (95% CI 0.69-0.89), p < 0.001, respectively. The AUC for prediction of 28-day mortality for MR-proADM and CT-proET-1 remained high over time. MR-proADM ≥1.57 nmol/L and CT-proET-1 ≥ 111 pmol/L at baseline were significant predictors for 28-day mortality (HR 6.80, 95% CI 3.12-14.84, p < 0.001 and HR 3.72, 95% CI 1.71-8.08, p 0.01). Baseline and serial MR-proADM and CT-proET-1 had good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia. NEDERLANDS TRIAL REGISTER, NL8460.

van Oers JAH ，Kluiters Y ，Bons JAP ，de Jongh M ，Pouwels S ，Ramnarain D ，de Lange DW ，de Grooth HJ ，Girbes ARJ ... -  《-》

Adrenomedullin and endothelin-1 are associated with myocardial injury and death in septic shock patients.

Lundberg OH ，Bergenzaun L ，Rydén J ，Rosenqvist M ，Melander O ，Chew MS ... -  《CRITICAL CARE》

Vasoregulatory peptides pro-endothelin-1 and pro-adrenomedullin are associated with metabolic syndrome in the population-based KORA F4 study.

Seissler J ，Feghelm N ，Then C ，Meisinger C ，Herder C ，Koenig W ，Peters A ，Roden M ，Lechner A ，Kowall B ，Rathmann W ... -  《-》