Dataset Information

Causal associations between insulin and Lp(a) levels in Caucasian population: a Mendelian randomization study.

ABSTRACT:

Background

Numerous observational studies have demonstrated that circulating lipoprotein(a) [Lp(a)] might be inversely related to the risk of type 2 diabetes (T2D). However, recent Mendelian randomization (MR) studies do not consistently support this association. The results of in vitro research suggest that high insulin concentrations can suppress Lp(a) levels by affecting apolipoprotein(a) [apo(a)] synthesis. This study aimed to identify the relationship between genetically predicted insulin concentrations and Lp(a) levels, which may partly explain the associations between low Lp(a) levels and increased risk of T2D.

Methods

Independent genetic variants strongly associated with fasting insulin levels were identified from meta-analyses of genome-wide association studies in European populations (GWASs) (N = 151,013). Summary level data for Lp(a) in the population of European ancestry were acquired from a GWAS in the UK Biobank (N = 361,194). The inverse-variance weighted (IVW) method approach was applied to perform two-sample summary-level MR. Robust methods for sensitivity analysis were utilized, such as MR‒Egger, the weighted median (WME) method, MR pleiotropy residual sum and outlier (MR-PRESSO), leave-one-out analysis, and MR Steiger.

Results

Genetically predicted fasting insulin levels were negatively associated with Lp(a) levels (β = - 0.15, SE = 0.05, P = 0.003). The sensitivity analysis revealed that WME (β = - 0.26, SE = 0.07, P = 0.0002), but not MR‒Egger (β = - 0.22, SE = 0.13, P = 0.11), supported a causal relationship between genetically predisposed insulin levels and Lp(a).

Conclusion

Our MR study provides robust evidence supporting the association between genetically predicted increased insulin concentrations and decreased concentrations of Lp(a). These findings suggest that hyperinsulinaemia, which typically accompanies T2D, can partially explain the inverse relationship between low Lp(a) concentrations and an increased risk of T2D.

SUBMITTER: Lejawa M

PROVIDER: S-EPMC11360791 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Causal associations between insulin and Lp(a) levels in Caucasian population: a Mendelian randomization study.

Lejawa Mateusz M Goławski Marcin M Fronczek Martyna M Osadnik Tadeusz T Paneni Francesco F Ruscica Massimiliano M Pawlas Natalia N Lisik Małgorzata M Banach Maciej M

Cardiovascular diabetology 20240829 1

<h4>Background</h4>Numerous observational studies have demonstrated that circulating lipoprotein(a) [Lp(a)] might be inversely related to the risk of type 2 diabetes (T2D). However, recent Mendelian randomization (MR) studies do not consistently support this association. The results of in vitro research suggest that high insulin concentrations can suppress Lp(a) levels by affecting apolipoprotein(a) [apo(a)] synthesis. This study aimed to identify the relationship between genetically predicted i ...[more]

PMID: 39210428

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Dataset Information

Causal associations between insulin and Lp(a) levels in Caucasian population: a Mendelian randomization study.

Background

Methods

Results

Conclusion

Publications

Causal associations between insulin and Lp(a) levels in Caucasian population: a Mendelian randomization study.

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