Evidence mapPaperPMID 39210428Full record

ArticleCardiovascular diabetology2024

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

Mateusz Lejawa, Marcin Goławski, Martyna Fronczek, Tadeusz Osadnik, Francesco Paneni, Massimiliano Ruscica, Natalia Pawlas, Małgorzata Lisik, Maciej Banach

Abstract read
In one paragraph

Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

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0cells of the map it votes in
10citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. The Implications of Lipoprotein(a) in MASLD.Current cardiology reports · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Mateusz LejawaDepartment of Pharmacology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland. mateusz.lejawa@sum.edu.pl.ORCID 0000-0002-1228-7534
Marcin GoławskiDepartment of Pharmacology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland.ORCID 0000-0001-7891-672X
Martyna FronczekDepartment of Pharmacology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland.ORCID 0000-0003-3669-1416
Tadeusz OsadnikDepartment of Pharmacology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland.ORCID 0000-0002-3202-6972
Francesco PaneniDepartment of Cardiology, University Heart Center, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.ORCID 0000-0001-6483-7844
Massimiliano RuscicaDepartment of Cardio-Thoracic-Vascular Diseases, Foundation IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.ORCID 0000-0002-0195-7061
Natalia PawlasDepartment of Pharmacology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland.ORCID 0000-0002-7551-9371
Małgorzata LisikOutpatient Clinic, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland.ORCID 0000-0002-4806-3022
Maciej BanachDepartment of Preventive Cardiology and Lipidology, Medical University of Lodz, Lodz, Poland.ORCID 0000-0001-6690-6874

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNumerous 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.

methodsIndependent 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.

resultsGenetically 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).

conclusionOur 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.

Indexed as

Diabetes Mellitus, Type 2InsulinLipoprotein(a)White PeopleBiomarkersFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMendelian Randomization AnalysisPhenotypePolymorphism, Single NucleotideRisk AssessmentRisk FactorsBiomarkersInsulinLipoprotein(a)LPA protein, humanInsulinLipoprotein(a)Mendelian randomization

Identifiers

PMID39210428
PMCPMC11360791

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.