Evidence map›Paper›PMID 27415606›Full record

ArticleClinical pharmacology and therapeutics2016

A Longitudinal HbA1c Model Elucidates Genes Linked to Disease Progression on Metformin.

S Goswami, S W Yee, F Xu, S B Sridhar, J D Mosley, A Takahashi, M Kubo, S Maeda, R L Davis, D M Roden and 3 more

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

Article in Clinical pharmacology and therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 21% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Genetic Variants inDiabetes · 2018
    Trial
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  11. Review
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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

13 authors at 6 institutions in 3 countries.

S GoswamiUniversity of California, San Francisco, San Francisco, California, USA.
S W YeeUniversity of California, San Francisco, San Francisco, California, USA.
F XuKaiser Permanente Northern California, Oakland, California, USA.
S B SridharKaiser Permanente Northern California, Oakland, California, USA.
J D MosleyVanderbilt University, Nashville, Tennessee, USA.
A TakahashiRIKEN Institute, Center for Genomic Medicine, Saitama, Japan.
M KuboRIKEN Institute, Center for Genomic Medicine, Saitama, Japan.
S MaedaRIKEN Institute, Center for Genomic Medicine, Saitama, Japan.
R L DavisKaiser Permanente Georgia, Atlanta, Georgia, USA.
D M RodenVanderbilt University, Nashville, Tennessee, USA.
M M HeddersonKaiser Permanente Northern California, Oakland, California, USA.
K M GiacominiUniversity of California, San Francisco, San Francisco, California, USA. Kathy.giacomini@ucsf.edu.
R M SavicUniversity of California, San Francisco, San Francisco, California, USA. rada.savic@ucsf.edu.
University of California, San Francisco · USKaiser Permanente · USRIKEN · JPVanderbilt University · USCenter for Genomic Science · ITUniversity of Tennessee Health Science Center · US

Funding

PHARMACOGENETICS OF MEMBRANE TRANSPORTERSU01GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GIACOMINI, KATHLEEN M · 2000 to 2009
$29.2M
Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2003 to 2019
$21.8M
Pharmacogenomics of Membrane TransportersU19GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WITTE, JOHN S. · 2010 to 2014
$16.3M
Equipment Supplement for Discovery of Pharmacogenomic Biomarkers for OATP1B1 and OATP1B3R01GM117163 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FLOREZ, JOSE CARLOS, HEDDERSON, MONIQUE MARIE · 2015 to 2023
$5.5M
American Heart Association-American Stroke Association 16FTF30130005NIDDK NIH HHS P30 DK063720NIGMS NIH HHS R01 GM117163NIGMS NIH HHS U01 GM061390NIGMS NIH HHS U19 GM061390
6 · The paper itself

Abstract

One-third of type-2 diabetic patients respond poorly to metformin. Despite extensive research, the impact of genetic and nongenetic factors on long-term outcome is unknown. In this study we combine nonlinear mixed effect modeling with computational genetic methodologies to identify predictors of long-term response. In all, 1,056 patients contributed their genetic, demographic, and long-term HbA1c data. The top nine variants (of 12,000 variants in 267 candidate genes) accounted for approximately one-third of the variability in the disease progression parameter. Average serum creatinine level, age, and weight were determinants of symptomatic response; however, explaining negligible variability. Two single nucleotide polymorphisms (SNPs) in CSMD1 gene (rs2617102, rs2954625) and one SNP in a pharmacologically relevant SLC22A2 gene (rs316009) influenced disease progression, with minor alleles leading to less and more favorable outcomes, respectively. Overall, our study highlights the influence of genetic factors on long-term HbA1c response and provides a computational model, which when validated, may be used to individualize treatment.

Indexed as

Disease ProgressionAdultAgedAged, 80 and overDiabetes Mellitus, Type 2FemaleGlycated HemoglobinHumansHypoglycemic AgentsLongitudinal StudiesMaleMembrane ProteinsMetforminMiddle AgedNonlinear DynamicsOrganic Cation Transporter 2CSMD1 protein, humanGlycated Hemoglobinhemoglobin A1c protein, humanHypoglycemic AgentsMembrane ProteinsMetforminOrganic Cation Transporter 2Organic Cation Transport ProteinsSLC22A2 protein, humanTumor Suppressor Proteins

Identifiers

PMID27415606
PMCPMC5534241
OpenAlexW2465940460

What OpenQuestion holds

Texttitle and abstract
LicenceTDM
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.