Longitudinal variability of lipoprotein(a) in youth-onset type 1 diabetes: implications for cardiovascular risk stratification

BACKGROUND: Lipoprotein(a) [Lp(a)] is a genetically determined and independent cardiovascular risk factor, traditionally considered stable across the lifespan, supporting a single lifetime measurement strategy. However, its longitudinal behaviour during childhood and adolescence remains poorly characterised, particularly in individuals with type 1 diabetes who face a markedly increased lifetime risk of coronary artery disease. We therefore aimed to characterise intra- and inter-individual trajectories of Lp(a) in a paediatric type 1 diabetes cohort and to assess the implications of Lp(a) variability for cardiovascular risk classification. METHODS: We conducted a retrospective single-centre cohort study of children and adolescents with type 1 diabetes attending Geneva University Hospitals between 2012 and 2023. Annual fasting Lp(a) concentrations were analysed longitudinally. Variability was assessed in participants with ≥ 2 measurements. Clinically relevant thresholds were used to evaluate cardiovascular risk reclassification. Paired Wilcoxon tests, Pearson and Kendall correlations, and Holm-adjusted p-values (P < 0.05) were applied. Analyses were conducted in R. RESULTS: A total of 286 participants contributed 1403 Lp(a) measurements, with observation periods varying across individuals (median 6.2 years, IQR 2.9-9.6) and between 1 and 13 measurements per participant. At baseline, 26% had elevated Lp(a) (≥ 300 mg/l). Among participants with serial measurements, 32% showed intraindividual fluctuations exceeding 50% of their individual maximum value. Reclassification across the 300 mg/l cardiovascular risk threshold occurred in 11.9% of participants. Lp(a) concentrations peaked between ages 10 and 13 years and declined thereafter. Modest seasonal variation was observed, with higher concentrations in autumn and winter (P < 0.05). CONCLUSIONS: In youth with type 1 diabetes, Lp(a) is not as stable as previously assumed, exhibiting clinically relevant variability over time. These findings challenge the current paradigm of a single lifetime Lp(a) measurement and suggest that repeated assessment, particularly during adolescence, may improve early cardiovascular risk stratification.