Abstract Body (Do not enter title and authors here): The relationship between LDL-C and the risk of developing T2D has been a subject of significant research interest. Observational studies and clinical trials have suggested that lower LDL-C levels, particularly when achieved through pharmacological interventions such as statins, are associated with an increased risk of T2D. However, the TG content of low-density lipoprotein (LDL-TG) has also been shown to be predictive of atherosclerotic cardiovascular disease (ASCVD) as LDL-C. However, its association with the development of T2D has not been explored. We have recently developed an equation for estimation LDL-TG which can also be calculated from the results of the standard lipid panel.
Methods: Our goal was to predict all-cause ASCVD and the development of T2D in a UK Biobank(n = 271,760). We excluded individuals on lipid-lowering treatment, preexisting ASCVD or T2D. We estimated LDL-TG, through our newly developed equation using the lipid panel, and LDL-C to determine individual risk. We performed Cox proportional hazard regression (HR) with all models adjusted for age, sex, race, systolic blood pressure, smoking and hypertension.
Results: A total of 271,760 participants with a median follow up of 10 years (IQR 6.7-12.3) were included for analysis. A total of 57% were female, with a mean age of 56.31 (SD 8) years. Covariable-adjusted HR for ASCVD in a comparison of the top with the bottom quintile for LDL-TG was 1.70 (95%CI,1.63 to1.77) and for LDL-C of 1.40 (95%CI, 1.35-1.47). A total 9,781participants developed T2D during the follow-up. Interestingly, the covariable-adjusted HR for developing T2D comparing the top with bottom quintile was of 4.62 (95CI, 4.25 to 5.04) for LDL-TG, while the HR for LDL-C was 0.93 (95%CI, 0.86-1). We performed a discordance analysis by plotting LDL-TG and LDL-C and grouping them in 4 groups by using the 50th percentile of LDL-TG (44mg/dL) and LDL-C (144mg/dL). Compared to having both LDL-TG and LDL-C below the 50^th percentile, having a discordantly high LDL-TG increased the risk for the developing T2D by 2.91 (95CI, 2.72 to 3.10) while having a discordantly high LDL-C reduced the risk with a HR of 0.81 (95%CI, 0.74 to 0.87). Having both above the 50^th percentile increased the risk for T2D with a HR 1.96 (95%CI, 1.85 to 2.08).
Conclusions: Our findings showed that LDL-TG is a stronger predictor of ASCVD than LDL-C. Having higher levels of LDL-TG were associated with a higher risk for developing T2D in a 10 year period.