Evidence map›Paper›PMID 39670999›Full record

ArticleDiabetologia2025

Genetic variation in the RETN promoter, accompanied by latent sarcopenic obesity, led to insulin resistance in a Japanese cohort: the Toon Genome Study.

Yosuke Ikeda, Ryoichi Kawamura, Yasuharu Tabara, Koutatsu Maruyama, Daisuke Shiokawa, Misaki Takakado, Toshimi Hadate, Yasunori Takata, Jun Ohashi, Isao Saito and 2 more

Abstract read
In one paragraph

Article in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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

2 citing papers in PubMed.

  1. Article
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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

12 authors.

Yosuke IkedaDepartment of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.
Ryoichi KawamuraDepartment of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.
Yasuharu TabaraGraduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.
Koutatsu MaruyamaDepartment of Bioscience, Graduate School of Agriculture, Ehime University, Ehime, Japan.
Daisuke ShiokawaTranslational Research Center, Ehime University, Ehime, Japan.
Misaki TakakadoDepartment of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.
Toshimi HadateDepartment of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.
Yasunori TakataDepartment of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.
Jun OhashiDepartment of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan.
Isao SaitoDepartment of Public Health and Epidemiology, Faculty of Medicine, Oita University, Oita, Japan.
Yoshihiro OgawaDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Haruhiko OsawaDepartment of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan. harosawa@m.ehime-u.ac.jp.

Funding

Clinical Research Promotion Foundation 2023 Z23-100084Japan Association for Diabetes Education and Care, and the Clinical Research Promotion Foundation Z22-100105JSPS KAKENHI 23K14738
6 · The paper itself

Abstract

aims/hypothesisResistin, inducing insulin resistance, is elevated in the sera of individuals with the G-A haplotype at c.-420 C>G (rs1862513) and c.-358 G>A (rs3219175). This haplotype is associated with visceral obesity and low grip strength. To elucidate the hidden relationship between the G-A haplotype and insulin resistance, integration of specific phenotypes defined by body composition and 75 g OGTT would be a promising strategy.

methodsThe 803 Japanese participants (average age: 62 years), attending annual medical checkups, were evaluated every 5 years. Participants were categorised by skeletal muscle mass, visceral fat score and OGTT results. Hierarchical clustering was performed using body composition and glucose metabolism parameters. Whole blood cells from participants homozygous for the G-A or C-G haplotype (n=25 and 33, respectively), matched for age, sex and BMI, using propensity score matching, were used for RNA-seq, pathway analysis and RT-PCR.

resultsMultivariate analysis showed that individuals with the G-A haplotype, when accompanied by latent skeletal muscle loss and visceral obesity (latent sarcopenic obesity), presented a pronounced deterioration in insulin resistance over a 5 year period. Cluster 2, identified using hierarchical clustering, was characterised by low skeletal muscle mass, visceral obesity and insulin resistance. This cluster, with the G-A haplotype, demonstrated deterioration in insulin resistance. RNA-seq and RT-PCR revealed altered expression of mitophagy-related genes in whole blood cells of the G-A homozygotes. CONCLUSIONS/

interpretationThe G-A haplotype, accompanied by latent low skeletal muscle mass and visceral obesity, led to the deterioration of insulin resistance over a 5 year period in this cohort, possibly through the altered expression of mitophagy-related genes.

Indexed as

Insulin ResistanceObesityPromoter Regions, GeneticSarcopeniaAgedBody CompositionCohort StudiesEast Asian PeopleFemaleGenetic VariationHaplotypesHumansJapanMaleMiddle AgedPolymorphism, Single NucleotideInsulin resistanceMitophagyOGTTResistinSkeletal muscle massSNPVisceral fat score

Identifiers

PMID39670999
PMCPMC11950018

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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 OpenQuestion graph.