Conditional Associations of ApoB and LDL ‐C With Incident Type 2 Diabetes in UK Biobank: A Prospective Cohort Study

AIMS: Although closely correlated, apolipoprotein B (apoB) reflects atherogenic particle number, whereas low-density lipoprotein cholesterol (LDL-C) measures cholesterol carried by LDL particles. We examined whether their associations with incident Type 2 diabetes (T2D) diverged after accounting for each other. MATERIALS AND METHODS: We included UK Biobank participants recruited in 2006-2010 without identified baseline diabetes. ApoB and LDL-C were assessed in baseline blood samples, and incident T2D was ascertained through 19 December 2022. Cause-specific Cox models estimated hazard ratios (HRs) per 10 mg/dL higher concentration. Primary models used the same participants and nonlipid covariates, with each biomarker entered individually and both entered in one model. Additional analyses assessed combined metabolic adjustment and time-varying associations. RESULTS: Among 402 144 participants followed for 5.33 million person-years, 16 537 developed T2D. ApoB and LDL-C were highly correlated (r = 0.958). When modelled individually, HRs per 10 mg/dL were 1.059 (95% CI: 1.052-1.066) for apoB and 1.018 (95% CI: 1.013-1.023) for LDL-C. When included together, summary HRs over the full follow-up were 1.502 (95% CI: 1.468-1.537) for apoB and 0.759 (95% CI: 0.745-0.772) for LDL-C. Combined cardiometabolic and HbA1c adjustment attenuated both conditional associations, with HRs of 1.151 (95% CI: 1.122-1.181) for apoB and 0.890 (0.873-0.908) for LDL-C. Time-varying HRs at Years 1 and 10 were 1.658 and 1.464 for apoB, and 0.691 and 0.777 for LDL-C, respectively. CONCLUSIONS: Higher apoB at a given LDL-C was associated with a higher hazard of incident T2D, whereas higher LDL-C at a given apoB was associated with a lower hazard.