Diabetes mellitus, glycemic traits, SGLT2 inhibition, and risk of pulmonary arterial hypertension: A Mendelian randomization study.
Biosci Trends
; 18(1): 94-104, 2024 Mar 19.
Article
in En
| MEDLINE
| ID: mdl-38325821
ABSTRACT
This study aimed to investigate the causal role of diabetes mellitus (DM), glycemic traits, and sodium-glucose cotransporter 2 (SGLT2) inhibition in pulmonary arterial hypertension (PAH). Utilizing a two-sample two-step Mendelian randomization (MR) approach, we determined the causal influence of DM and glycemic traits (including insulin resistance, glycated hemoglobin, and fasting insulin and glucose) on the risk of PAH. Moreover, we examined the causal effects of SGLT2 inhibition on the risk of PAH. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene that were associated with both levels of gene expression and hemoglobin A1c. Results showed that genetically inferred DM demonstrated a causal correlation with an increased risk of PAH, exhibiting an odds ratio (OR) of 1.432, with a 95% confidence interval (CI) of 1.040-1.973, and a p-value of 0.028. The multivariate MR analysis revealed comparable outcomes after potential confounders (OR = 1.469, 95%CI = 1.021-2.115, p = 0.038). Moreover, genetically predicted SGLT2 inhibition was causally linked to a reduced risk of PAH (OR = 1.681*10-7, 95%CI = 7.059*10-12-0.004, p = 0.002). Therefore, our study identified the suggestively causal effect of DM on the risk of PAH, and SGLT2 inhibition may be a potential therapeutic target in patients with PAH.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diabetes Mellitus, Type 2
/
Pulmonary Arterial Hypertension
Type of study:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Biosci Trends
Journal subject:
BIOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Japan