Type 2 diabetes and fasting glycemic traits are causal factors of frozen shoulder: a 2-sample Mendelian randomization analysis.

Abstract

The causal relationship between type 2 diabetes (T2D) and frozen shoulder is unclear. This study aims to explore the genetic causal association between T2D and glycemic traits (fasting glucose [FG], fasting insulin [FI], glycated hemoglobin [HbA_1c], and 2-hour postprandial glucose [2hGlu]) on frozen shoulder. Using 2-sample Mendelian randomization (MR), we analyzed nonconfounded estimates of the effects of T2D and glycemic traits on frozen shoulder. Single-nucleotide polymorphisms (SNPs) strongly associated (P < 5 × 10^-8) with exposures from genome-wide association studies (GWAS) were identified. We employed fixed effect mode inverse variance weighting (IVW-FE), random effect mode IVW (IVW-MRE), MR-Egger, and weighted median to assess the association of exposures and outcome. Sensitivity analysis was conducted to test for heterogeneity and multidirectionality bias in MR. We found a significant genetic causal correlation between T2D (IVW-MRE P = .007, odds ratio [OR] 1.093, 95% confidence interval [CI] 1.03-1.16), FG (IVW-FE P < .001, OR 1.455, 95% CI 1.173-1.806), and frozen shoulder, but no evidence for causal correlation between FI, HbA_1c, and 2hGlu and frozen shoulder. Although there was certain heterogeneity, sensitivity analysis reveals no deviation from the MR assumptions. This study supports a genetic causal relationship between T2D and FG and frozen shoulder.