Remnant Cholesterol and Cardiovascular Risk in Adults With Type 1 Diabetes: A Nested Case-Control Study

Despite advancements in therapeutic strategies, adults with type 1 diabetes (T1D) remain at high risk of cardiovascular disease (CVD). Traditional lipid parameters may not fully account for this residual risk. Remnant cholesterol-found in triglyceride-rich lipoproteins such as VLDL and IDL-has emerged as a potential contributor to atherogenesis but has not been extensively studied in T1D.

We conducted a nested case-control study within a multicentre Spanish cohort of 2187 adults with T1D. A total of 88 cases with a first CVD event (2010-2024) were matched 1:1 to controls by age, sex, diabetes duration, HbA1c, smoking, hypertension and retinopathy. Remnant cholesterol was calculated as total cholesterol minus HDL-C and LDL-C. Multivariable conditional logistic regression was used to assess associations with CVD. A stratified analysis by LDL-C quartiles was also performed to explore potential effect modification.

The mean age of participants was 59.9 ± 12.1 years, 34.7% were female, the median duration of diabetes was 27.9 ± 13.3 years and mean HbA1c was 7.9%±1.3%. Remnant cholesterol levels in the highest quartile (> 28 mg/dL) were independently associated with increased risk of CVD (OR = 4.50; 95% CI: 1.34-15.08; p = 0.015). This association was evident only among individuals with LDL-C ≥ 100 mg/dL, while no significant relationship was observed in those with LDL-C < 100 mg/dL. A linear trend across LDL-C strata further supported a dose-response relationship. HDL-C < 45 mg/dL and triglycerides in the highest quartile were also associated with increased CVD risk. Notably, most participants did not achieve LDL-C targets and 41.4% were untreated.

Elevated remnant cholesterol is an independent predictor of cardiovascular disease in adults with T1D, particularly in those with suboptimally controlled LDL cholesterol. These findings highlight the importance of achieving LDL-C treatment goals and considering remnant cholesterol in cardiovascular risk assessment, supporting the need for targeted lipid-lowering strategies in T1D.