Causal relationship between frailty and diabetes subtypes: A bidirectional Mendelian randomization study.

Area of Science:

• Gerontology
• Endocrinology
• Genetic Epidemiology

Background:

• Frailty and diabetes mellitus (DM) share a complex relationship, but the causal direction remains uncertain.
• Understanding this bidirectional link is crucial for effective clinical management.

Purpose of the Study:

• To investigate the bidirectional causal relationship between frailty and various diabetes mellitus subtypes using Mendelian randomization (MR).

Main Methods:

• A 2-sample MR analysis was conducted using large-scale genome-wide association study summary statistics.
• Inverse-variance weighting was the primary method, with MR-Egger regression and weighted median for sensitivity.
• MR-PRESSO and Cochran Q tests assessed pleiotropy and heterogeneity.

Main Results:

• Genetically predicted frailty significantly increased the risk of type 2 diabetes (T2DM) and gestational diabetes (GDM).
• Conversely, genetically predicted T1DM, T2DM, GDM, and elevated 2-hour post-load glucose levels were associated with increased frailty risk.
• No significant causal links were found between frailty and type 1 diabetes or other glycemic traits.

Conclusions:

• This study provides robust genetic evidence for a bidirectional causal relationship between frailty and diabetes, particularly T2DM and GDM.
• Findings underscore the importance of frailty screening in diabetic patients and metabolic control in frail individuals.