Evidence mapPaperPMID 30352097Full record

SynthesisPloS one2018

Association of common gene variants in glucokinase regulatory protein with cardiorenal disease: A systematic review and meta-analysis.

Pomme I H G Simons, Nynke Simons, Coen D A Stehouwer, Casper G Schalkwijk, Nicolaas C Schaper, Martijn C G J Brouwers

Registry-linked trialOpen access · goldAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06222476 (A Multicentric, Prospective, Randomized Study Evaluating the Improvement of Renal Function Outcomes With Dorzagliatin in Patients With Type 2 Diabetes Mellitus With Early Kidney Injury.), which is not on this map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.1field-weighted citation impact, top 9% 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.

NCT06222476 naunknown statusnot on this mapstarted 2024, after this paper: background citation

A Multicentric, Prospective, Randomized Study Evaluating the Improvement of Renal Function Outcomes With Dorzagliatin in Patients With Type 2 Diabetes Mellitus With Early Kidney Injury.

TypeinterventionalSponsorYan BiRan2024 to 2026Enrolled106ConditionsDiabetic Nephropathy Type 2ArmsDorzagliatin, Gliclazide
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Review
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  7. Review
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  9. Relationship betweenThe Journal of international medical research · 2021
    Article
  10. Article
  11. The endothelial function biomarker soluble E-selectin is associated with nonalcoholic fatty liver disease.Liver international : official journal of the International Association for the Study of the Liver · 2020
    Article
  12. Review
  13. Review
  14. Review
  15. Article
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

6 authors at 1 institution in 1 country.

Pomme I H G SimonsDepartment of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, Maastricht, The Netherlands.
Nynke SimonsDepartment of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, Maastricht, The Netherlands.
Coen D A StehouwerDepartment of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
Casper G SchalkwijkDepartment of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
Nicolaas C SchaperDepartment of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, Maastricht, The Netherlands.
Martijn C G J BrouwersDepartment of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, Maastricht, The Netherlands.ORCID 0000-0002-8229-3331
Maastricht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSmall-molecules that disrupt the binding between glucokinase and glucokinase regulatory protein (GKRP) in the liver represent a potential new class of glucose-lowering drugs. It will, however, take years before their effects on clinically relevant cardiovascular endpoints are known. The purpose of this study was to estimate the effects of these drugs on cardiorenal outcomes by studying variants in the GKRP gene (GCKR) that mimic glucokinase-GKRP disruptors.

methodsThe MEDLINE and EMBASE databases were searched for studies reporting on the association between GCKR variants (rs1260326, rs780094, and rs780093) and coronary artery disease (CAD), estimated glomerular filtration rate (eGFR), and chronic kidney disease (CKD).

resultsIn total 5 CAD studies (n = 274,625 individuals), 7 eGFR studies (n = 195,195 individuals), and 4 CKD studies (n = 31,642 cases and n = 408,432 controls) were included. Meta-analysis revealed a significant association between GCKR variants and CAD (OR:1.02 per risk allele, 95%CI:1.00-1.04, p = 0.01). Sensitivity analyses showed that replacement of one large, influential CAD study by two other, partly overlapping studies resulted in similar point estimates, albeit less precise (OR:1.02; 95%CI:0.98-1.06 and OR: 1.02; 95%CI: 0.99-1.04). GCKR was associated with an improved eGFR (+0.49 ml/min, 95%CI:0.10-0.89, p = 0.01) and a trend towards protection from CKD (OR:0.98, 95%CI:0.95-1.01, p = 0.13).

conclusionThis study suggests that increased glucokinase-GKRP disruption has beneficial effects on eGFR, but these may be offset by a disadvantageous effect on coronary artery disease risk. Further studies are warranted to elucidate the mechanistic link between hepatic glucose metabolism and eGFR.

Indexed as

Polymorphism, Single NucleotideAllelesCarrier ProteinsCoronary Artery DiseaseGlomerular Filtration RateGlucokinaseHumansProtein BindingRenal Insufficiency, ChronicSmall Molecule LibrariesCarrier ProteinsGlucokinaseglucokinase regulatory proteinSmall Molecule Libraries

Identifiers

PMID30352097
PMCPMC6198948
OpenAlexW2897740223

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.