Key result
Higher baseline concentrations of CT-proET-1 and MR-proADM were associated with an increased risk of incident type 2 diabetes, with hazard ratios of 1.10 and 1.11 per 1-SD increase, respectively.
Why the study?
Endothelin-1 and adrenomedullin regulate vascular homeostasis, but whether they affect glucose metabolism and are associated with incident type 2 diabetes remains less recognized.
Do higher concentrations of vasoactive peptides CT-proET-1 and MR-proADM predict incident type 2 diabetes in individuals without baseline diabetes or cardiovascular disease?
Cohort (n=12,006)
Yes
Do higher concentrations of vasoactive peptides CT-proET-1 and MR-proADM predict incident type 2 diabetes in individuals without baseline diabetes or cardiovascular disease?
Higher circulating concentrations of CT-proET-1 and MR-proADM are associated with an increased risk of incident type 2 diabetes, with Mendelian randomization supporting a potential causal role for CT-proET-1.
Answers are grounded in this paper and cite their sources.
May refine diabetes risk stratification; leaves open causal roles and clinical utility.
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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Sujana et al. (2022) conducted a cohort in Incident type 2 diabetes (n=12,006). CT-proET-1 was evaluated on Incident type 2 diabetes (HR 1.10, 95% CI 1.03; 1.18, p=0.008). Higher baseline concentrations of CT-proET-1 and MR-proADM were associated with an increased risk of incident type 2 diabetes, with hazard ratios of 1.10 and 1.11 per 1-SD increase, respectively.
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