Abstract
Background
Despite substantial research investigating the relationship between Type 2 Diabetes (T2D) and Heart Failure (HF), the specifics and dynamics of this correlation remain a subject of debate. This study seeks to elucidate the genetic determinants underlying the causal relationship between T2D and HF.
Methods
Genetic analyses were performed utilizing summary statistics derived from recent, extensive Genome-Wide Association Studies (GWASs), focusing on T2D, HF and various mediators. Linkage disequilibrium score regression (LDSC) analysis and both univariable and multivariable Mendelian Randomization (MR) analyses were employed to assess the causal relationships among these conditions. The primary approach for MR analysis was the inverse-variance weighted method.
Results
LDSC analysis identified a significant genetic correlation between T2D and HF. Univariable MR analyses demonstrated that genetically inferred T2D was causally linked to an increased risk of both HF and chronic heart failure (CHF). Reverse MR analysis indicated a potential genetic causal relationship from CHF to T2D. However, no significant genetic causal relationships were detected between glycemic traits in non-diabetic population and HF. When adjusting for body mass index, waist-hip ratio (WHR), systolic blood pressure (SBP), and coronary artery disease in multivariate MR, the association between T2D and HF was vanished, particularly for SBP, and likely for WHR. The MR findings relating to T2D and left ventricular function traits further reinforced this evidence.
Conclusions
Our research suggests that SBP is likely a primary mediator in the relationship between T2D and HF, with the influence of WHR on this association also meriting closer examination. Effective management of blood pressure in patients with T2D, dependent of glucose level control, is crucial for reducing the risk of heart failure complication. Moderate weight control strategies targeting WHR may possess certain significance.