Epidemiology
Lp(a) lowers type 2 diabetes risk only in severe prediabetes, UK Biobank analysis (Diabetes Metab Syndr 2026)
Original title: The effect of baseline prediabetes on the relation between lipoprotein (a) and incident type 2 diabetes mellitus and cardiovascular outcomes: observations from the UK-Biobank
UK Biobank analysis of adults without diabetes, stratified by baseline HbA1c into normoglycaemia (below 5.7%), mild prediabetes (5.7-6.0%) and severe prediabetes (6.0% or more), testing whether prediabetes modifies the Lp(a)-outcome relationship over 11.9 years (3.3% developed type 2 diabetes). Overall, higher Lp(a) quartiles carried 7-11% lower diabetes risk than the lowest quartile, but this inverse association was significant only in the severe-prediabetes group (quartile 3: HR 0.88, 95% CI 0.80-0.98; quartile 4: HR 0.82, 95% CI 0.74-0.91). Major adverse cardiovascular events (MACE) were higher in the upper Lp(a) quartiles in the whole cohort and the normoglycaemia group (quartile 3: HR 1.04; quartile 4: HR 1.16) and quartile 4 only in mild prediabetes (HR 1.14), but Lp(a) quartiles showed no MACE difference in severe prediabetes. The authors conclude Lp(a)'s inverse link to diabetes risk appears only with severe prediabetes, while its direct cardiovascular risk association is seen mainly without prediabetes.
Original abstract
Aims: To explore the effect of prevalent prediabetes (preDM) on relation between lipoprotein (a) Lp(a) and incident diabetes mellitus (T2DM) and cardiovascular outcomes.
Method: Subjects without diabetes with available Lp(a) in UK-Biobank database, were divided into Group 1 (HbA1c <5.7%, (39 mmol/mol)), Group 2 (HbA1c 5.7-<6.0% (39-<42 mmol/mol)) and Group 3 (HbA1c ≥ 6.0% (42 mmol/mol)). Incident T2DM and major adverse cardiovascular event (MACE) (death, non-fatal myocardial infarction, ischaemic stroke, or coronary revascularisation) during follow up was identified. The unadjusted and adjusted risk of T2DM and MACE between Lp(a) quartiles was estimated in the 3 groups.
Results: 11.9 years follow up; 3.3% subjects developed T2DM. Lp(a) Q2-4 had 7-11% lower risk of T2DM compared to Q1. Adjusted risk of T2DM was lower in Q3 (HR 0.88, 0.80-0.98, p = 0.017) and Q4 (HR 0.82, 0.74-0.91, p < 0.001) only in Group 3. MACE was higher in Q3 and Q4 in whole cohort and Group 1(Q3: HR 1.04, 1.01-1.08, p = 0.025; Q4: HR 1.16, 1.11-1.20, p < 0.0001) but only in Q4 (HR 1.14, 1.07-1.23, p = 0.0002) in Group 2. MACE was similar between quartiles in Group 3.
Conclusion: Lp(a) is inversely related to T2DM risk only in subjects with severe prediabetes. Direct association between Lp(a) and cardiovascular outcomes is seen only in subjects without prediabetes.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.