Higher lipoprotein(a) (Lp[a]) levels were associated with a lower risk of incident type 2 diabetes mellitus (T2DM) only in individuals with more advanced prediabetes, according to an observational analysis of UK Biobank data published in Diabetes & Metabolic Syndrome: Clinical Research & Reviews. The analysis also assessed the relationship between Lp(a) and major adverse cardiovascular events (MACE), with findings varying across glycemic strata.

The analysis included nondiabetic adults with available Lp(a) data and stratified them into three groups based on glycated hemoglobin (HbA1c): Group 1 (<5.7% [<39 mmol/mol]), Group 2 (5.7-<6.0% [39-<42 mmol/mol]), and Group 3 (≥6.0% [≥42 mmol/mol]). Outcomes included incident T2DM and MACE, defined as death, nonfatal myocardial infarction, ischemic stroke, or coronary revascularization, during a median follow-up of 11.9 years.

During follow-up, 3.3% of participants developed T2DM. Compared with the lowest Lp(a) quartile (Q1), higher quartiles (Q2-Q4) were associated with a 7–11% lower risk of T2DM; however, after adjustment, this association remained significant only in Group 3, with Q3 showing a hazard ratio (HR) of 0.88 (95% CI, 0.80–0.98; p=0.017) and Q4 an HR of 0.82 (95% CI, 0.74-0.91; p<0.001).

For cardiovascular outcomes, MACE risk was higher in Q3 (HR 1.04; 95% CI, 1.01-1.08; p=0.025) and Q4 (HR 1.16; 95% CI, 1.11-1.20; p<0.0001) in the overall cohort and in Group 1. In Group 2, only Q4 showed a higher risk (HR 1.14; 95% CI, 1.07-1.23; p=0.0002), while no differences were observed across quartiles in Group 3. Overall, Lp(a) showed an inverse association with T2DM risk only in individuals with severe prediabetes, with heterogeneous associations observed for cardiovascular outcomes across glycemic groups.