Key result
Higher apoB is linked to ~50% higher incident T2D risk per 10 mg/dL.
Why the study?
Although apoB and LDL-C are closely correlated, apoB reflects atherogenic particle number while LDL-C measures cholesterol carried by LDL particles. Whether their associations with incident T2D diverge after accounting for each other was examined.
Do baseline concentrations of apolipoprotein B and LDL-C have diverging associations with incident Type 2 diabetes after accounting for each other in adults without baseline diabetes?
Cohort (n=402,144)
Yes
Do baseline concentrations of apolipoprotein B and LDL-C have diverging associations with incident Type 2 diabetes after accounting for each other in adults without baseline diabetes?
In a large prospective cohort, higher apoB at a given LDL-C concentration was associated with an increased hazard of incident Type 2 diabetes, whereas higher LDL-C at a given apoB concentration was associated with a lower hazard.
Hypothesis-generating for apoB as a distinct metabolic risk marker; leaves open whether atherogenic particle number causally drives diabetes independently of LDL-C.
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.
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Xue et al. (2026) conducted a cohort in Incident Type 2 diabetes (n=402,144). Baseline apolipoprotein B (apoB) and low-density lipoprotein cholesterol (LDL-C) levels (per 10 mg/dL higher concentration) vs. Lower biomarker concentrations (continuous per 10 mg/dL, modelled individually and mutually adjusted) was evaluated on Incident Type 2 diabetes (T2D) (HR 1.502 for apoB; HR 0.759 for LDL-C (mutually adjusted per 10 mg/dL), 95% CI 1.468-1.537). Per 10 mg/dL increase in mutually adjusted models, apoB increased incident T2D risk (HR 1.502; 95% CI 1.468-1.537) while LDL-C decreased it (HR 0.759; 95% CI 0.745-0.772).
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