Evidence map›Paper›PMID 34505161›Full record

ArticleDiabetologia2021

Leveraging human genetic data to investigate the cardiometabolic effects of glucose-dependent insulinotropic polypeptide signalling.

Ville Karhunen, Iyas Daghlas, Verena Zuber, Marijana Vujkovic, Anette K Olsen, Lotte Bjerre Knudsen, William G Haynes, Joanna M M Howson, Dipender Gill

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.2field-weighted citation impact, top 11% of its field
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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

19 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Leveraging Mendelian randomization to inform drug discovery and development for ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
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 at 8 institutions in 4 countries.

Ville KarhunenDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK. v.karhunen@imperial.ac.uk.ORCID 0000-0001-6064-1588
Iyas DaghlasHarvard Medical School, Boston, MA, USA.ORCID 0000-0001-8735-284X
Verena ZuberDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK.ORCID 0000-0001-9827-1877
Marijana VujkovicCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID 0000-0003-4924-5714
Anette K OlsenGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.ORCID 0000-0001-9352-621X
Lotte Bjerre KnudsenGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.ORCID 0000-0002-2439-7116
William G HaynesNovo Nordisk Research Centre Oxford, Old Road Campus, Oxford, UK.ORCID 0000-0003-1004-6136
Joanna M M HowsonNovo Nordisk Research Centre Oxford, Old Road Campus, Oxford, UK.ORCID 0000-0001-7618-0050
Dipender GillDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK. dipender.gill@imperial.ac.uk.ORCID 0000-0001-7312-7078
Novo Nordisk (Denmark) · DKHarvard University · USImperial College London · GBMRC Biostatistics Unit · GBNovo Nordisk (United Kingdom) · GBPhiladelphia VA Medical Center · USSt George's, University of London · GBUniversity of Oxford · GB

Funding

British Heart Foundation RE/18/4/34215Department of Health CL-2020-16-001
6 · The paper itself

Abstract

aims/hypothesisThe aim of this study was to leverage human genetic data to investigate the cardiometabolic effects of glucose-dependent insulinotropic polypeptide (GIP) signalling.

methodsData were obtained from summary statistics of large-scale genome-wide association studies. We examined whether genetic associations for type 2 diabetes liability in the GIP and GIPR genes co-localised with genetic associations for 11 cardiometabolic outcomes. For those outcomes that showed evidence of co-localisation (posterior probability >0.8), we performed Mendelian randomisation analyses to estimate the association of genetically proxied GIP signalling with risk of cardiometabolic outcomes, and to test whether this exceeded the estimate observed when considering type 2 diabetes liability variants from other regions of the genome.

resultsEvidence of co-localisation with genetic associations of type 2 diabetes liability at both the GIP and GIPR genes was observed for five outcomes. Mendelian randomisation analyses provided evidence for associations of lower genetically proxied type 2 diabetes liability at the GIP and GIPR genes with lower BMI (estimate in SD units -0.16, 95% CI -0.30, -0.02), C-reactive protein (-0.13, 95% CI -0.19, -0.08) and triacylglycerol levels (-0.17, 95% CI -0.22, -0.12), and higher HDL-cholesterol levels (0.19, 95% CI 0.14, 0.25). For all of these outcomes, the estimates were greater in magnitude than those observed when considering type 2 diabetes liability variants from other regions of the genome. CONCLUSIONS/

interpretationThis study provides genetic evidence to support a beneficial role of sustained GIP signalling on cardiometabolic health greater than that expected from improved glycaemic control alone. Further clinical investigation is warranted. DATA AVAILABILITY: All data used in this study are publicly available. The scripts for the analysis are available at: https://github.com/vkarhune/GeneticallyProxiedGIP .

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Receptors, Gastrointestinal HormoneGastric Inhibitory PolypeptideGenome-Wide Association StudyGlucoseHuman GeneticsHumansGastric Inhibitory PolypeptideGlucoseReceptors, Gastrointestinal HormoneCardiometabolic diseaseCo-localisationGlucose-dependent insulinotropic polypeptideMendelian randomisationType 2 diabetes mellitus

Identifiers

PMID34505161
PMCPMC8563538
OpenAlexW3196975298

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.