Abstract

Context 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 behavior during childhood and adolescence remains poorly characterized, particularly in individuals with type 1 diabetes who are at increased lifetime risk of cardiovascular disease.

Objective We aimed to characterize intra- and inter-individual trajectories of Lp(a) in youth with type 1 diabetes and to assess the implications of variability for cardiovascular risk classification.

Methods We conducted a retrospective single-center cohort study of children and adolescents with type 1 diabetes followed at Geneva University Hospitals between 2012 and 2023. Annual fasting Lp(a) concentrations were analyzed longitudinally. Variability was assessed in participants with more than two measurements. Clinically relevant thresholds were used to evaluate risk reclassification. Statistical analyses included paired Wilcoxon tests, Pearson and Kendall correlations, and Holm-adjusted p-values.

Results A total of 287 participants contributed 1,408 Lp(a) measurements over a median follow-up of 6.2 years (IQR 2.9–9.6). At baseline, 26% had elevated Lp(a) (above or equal 300 mg/L). Among participants with serial measurements, 32% exhibited intraindividual fluctuations exceeding 50% of their maximum value. Reclassification across the 300 mg/L 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 levels in autumn and winter (P < 0.05).

Conclusions In youth with type 1 diabetes, Lp(a) demonstrates clinically relevant intraindividual variability over time. These findings suggest that reliance on a single lifetime measurement may lead to misclassification of cardiovascular risk and support repeated assessment, particularly during adolescence, to improve risk stratification.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Foundation Prim Enfance to V.M.S. Foundation Recherche pour le diabete to V.M.S. HUG Research Encouragement Grant to F.I.L.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by the Geneva, Switzerland Ethics Committee (CCER 2022-02251) and conducted in accordance with the principles of the Declaration of Helsinki.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Footnotes

Grants: Foundation “Prim’Enfance” to V.M.S., Foundation “Recherche pour le diabète” to V.M.S., HUG Research Encouragement Grant to F.I.L.

Disclosure: The authors have nothing to disclose.

Data Availability

Deidentified data are available from the corresponding author upon reasonable request and with appropriate justification, in accordance with institutional and ethical regulations.

AbbreviationsCVDCardiovascular diseaseHDL-CHigh-density lipoprotein cholesterolLDL-CLow-density lipoprotein cholesterolLp(a)Lipoprotein (a)