Relationship between remnant cholesterol and the risk of diabetic microvascular complications in type 2 diabetes: An observational study

Background Diabetic microvascular complications (DMCs) are a major contributor to morbidity in type 2 diabetes (T2D), yet the role of remnant cholesterol (RC) in their development remains unclear. This study aimed to investigate the association between RC levels and DMC risk in patients with T2D. Methods This prospective cohort study was conducted using Mendelian randomization analysis and data from the United Kingdom Biobank, including 22,270 older adults with T2D at baseline (median age: 61 y; 40% women). Participants were grouped according to low, medium, and high RC levels. The main outcome measures were prevalence of diabetic nephropathy, neuropathy, and retinopathy based on hospital admissions and mortality data. Results Increased RC levels were significantly associated with an increased risk of composite microvascular complications (hazard ratio [HR] for highest vs. lowest tertiles = 1.13, 95% confidence interval [CI]: 1.04–1.23), particularly diabetic nephropathy (HR = 1.19, 95% CI: 1.08–1.31) and neuropathy (HR = 1.22, 95% CI: 1.04–1.43). Mendelian randomization revealed statistically significant causal relationships between genetically predicted RC levels and diabetic nephropathy ( p  = 0.035) and retinopathy ( p  = 0.044). Restricted cubic spline analysis revealed a significant nonlinear dose–response relationship between RC levels and the risk of composite microvascular complications and diabetic retinopathy. Conclusions Elevated RC levels were independently associated with the risk of DMCs, particularly nephropathy and neuropathy. The Mendelian randomization results support a causal role of RC in nephropathy. These results suggest the potential role of RC as a biomarker and that it can aid in the early screening and prediction of diabetic microvascular damage.