Evidence map›Paper›PMID 26868433›Full record

Observational studyNutrition, metabolism, and cardiovascular diseases : NMCD2016

Is common genetic variation at IRS1, ENPP1 and TRIB3 loci associated with cardiometabolic phenotypes in type 2 diabetes? An exploratory analysis of the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 5.

M Trombetta, M Dauriz, S Bonetti, D Travia, L Boselli, L Santi, E Bonora, R C Bonadonna

2 registry-linked trialsAbstract readObservational Study
PubMed Publisher
In one paragraph

Observational study in Nutrition, metabolism, and cardiovascular diseases : NMCD, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.9field-weighted citation impact, top 20% 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.

NCT04271189 phase3completedstarted 2020, after this paper: background citation

A Prospective, Randomized, Parallel-group, Adaptive Design Phase IIb/III, Multicenter Study, to Assess the Efficacy of Polychemotherapy for Inducing Remission of Newly Diagnosed Type 2 Diabetes.

Ran2020Enrolled108Registered outcomes10Posted comparisons0ConditionsNewly Diagnosed Type 2 DiabetesArmsMetformin-Sitagliptin-Empaglifozin-Pioglitazone, Standard of care
PMID 17914032PMID 23116881PMID 26138864PMID 24463454PMID 11832527PMID 23354123PMID 26696678PMID 26670418PMID 26378978PMID 24315620PMID 24738668PMID 34462270other papers from this trial
Open the trial in the graph
NCT01526720 unknown statusnot on this map

The Verona Newly Diagnosed Type 2 Diabetes Study. Construction of a Biobank of Diabetes Related Genotypes and Phenotypes

TypeobservationalSponsorUniversita di VeronaRan2003 to 2020Enrolled1,500ConditionsType 2 Diabetes Mellitus
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

8 authors at 2 institutions in 1 country.

M TrombettaDepartment of Medicine, University of Verona, Verona, Italy; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Hospital Trust of Verona, Verona, Italy.
M DaurizDepartment of Medicine, University of Verona, Verona, Italy; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Hospital Trust of Verona, Verona, Italy.
S BonettiDepartment of Medicine, University of Verona, Verona, Italy.
D TraviaDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, Hospital Trust of Verona, Verona, Italy.
L BoselliDepartment of Medicine, University of Verona, Verona, Italy.
L SantiDepartment of Medicine, University of Verona, Verona, Italy.
E BonoraDepartment of Medicine, University of Verona, Verona, Italy; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Hospital Trust of Verona, Verona, Italy.
R C BonadonnaDepartment of Clinical and Experimental Medicine, University of Parma School of Medicine, Italy; Division of Endocrinology, Azienda Ospedaliera Universitaria, Parma, Italy. Electronic address: riccardo.bonadonna@unipr.it.
University of Verona · ITOspedale di Parma · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsInsulin resistance is a hallmark of type 2 diabetes (T2DM), it is often accompanied by defective beta-cell function (BF) and is involved in the pathophysiology of cardiovascular disease (CVD). Commonalities among these traits may recognize a genetic background, possibly involving the genetic variation of insulin signaling pathway genes. We conducted an exploratory analysis by testing whether common genetic variability at IRS1, ENPP1 and TRIB3 loci is associated with cardiovascular risk traits and metabolic phenotypes in T2DM. METHODS AND

resultsIn 597 drug-naïve, GADA-negative, newly-diagnosed T2DM patients we performed: 1) genotyping of 10 independent single-nucleotide polymorphisms covering ∼ 90% of common variability at IRS1, ENPP1 and TRIB3 loci; 2) carotid artery ultrasound; 3) standard ECG (n = 450); 4) euglycaemic insulin clamp to assess insulin sensitivity; 5) 75 g-OGTT to estimate BF (derivative and proportional control) by mathematical modeling. False discovery rate of multiple comparisons was set at 0.20. After adjustment for age, sex and smoking status, rs4675095-T (IRS1) and rs4897549-A (ENPP1) were significantly associated with carotid atherosclerosis severity, whilst rs7265169-A (TRIB3) was associated with ECG abnormalities. Rs858340-G (ENPP1) was significantly associated with decreased insulin sensitivity, independently of age, sex and body-mass-index. No consistent relationships were found with BF.

conclusionSome associations were found between intermediate phenotypes of CVD and common genetic variation of gatekeepers along the insulin signaling pathway. These results need be replicated to support the concept that in T2DM the CVD genetic risk clock may start ticking long before hyperglycemia appears. ClinicalTrials.gov Identifier: NCT01526720.

Indexed as

Polymorphism, Single NucleotideAgedBody Mass IndexCardiovascular DiseasesCell Cycle ProteinsCross-Sectional StudiesDiabetes Mellitus, Type 2FemaleGenotypeGenotyping TechniquesGlycated HemoglobinHumansInsulin Receptor Substrate ProteinsInsulin ResistanceLogistic ModelsMaleCell Cycle Proteinsectonucleotide pyrophosphatase phosphodiesterase 1Glycated HemoglobinInsulin Receptor Substrate ProteinsIRS1 protein, humanPhosphoric Diester HydrolasesProtein Serine-Threonine KinasesPyrophosphatasesRepressor ProteinsTRIB3 protein, humanCardiovascular disease riskGenetic associationInsulin resistanceSubclinical atherosclerosisType 2 diabetes

Identifiers

PMID26868433
OpenAlexW2260892240

What Socratic holds

Textmetadata
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.