Abstract
Visceral adiposity is a pivotal pathogenic driver of type 2 diabetes mellitus (T2DM) and its vascular complications. We performed two-sample Mendelian randomization (MR) analyses to examine the causal relationships between visceral adipose tissue (VAT) accumulation and diabetes complications. Single nucleotide polymorphisms (SNPs) specific to VAT accumulation were identified through large-scale genome-wide association studies (GWAS) at genome-wide significance (P < 5 × 10(-8)), using the inverse variance weighted (IVW) approach for primary analyses. The MR-IVW random-effects model revealed significant associations between genetically predicted VAT accumulation and increased risks for T2DM complications: multi-organ (OR = 2.58, 95% CI, 2.21-3.03), neurological (OR = 3.58, 95% CI, 2.34-5.47), retinopathy (OR = 2.90, 95% CI, 2.21-3.81), nephropathy (OR = 3.14, 95% CI, 2.23-4.45), and peripheral vascular (OR = 3.32, 95% CI, 2.31-4.76). Consistency across complementary MR methods supported the causal inference. This study provides genetic evidence that VAT accumulation is causally associated with increased risk of multiple T2DM complications, including neurological, ocular, kidney, and peripheral vascular outcomes. Future research should prioritize mechanistic studies to elucidate VAT-driven inflammatory and lipotoxic pathways in diabetic complications.