Evidence map›Paper›PMID 27841877›Full record

ArticleNature genetics2017

Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

Luca A Lotta, Pawan Gulati, Felix R Day, Felicity Payne, Halit Ongen, Martijn van de Bunt, Kyle J Gaulton, John D Eicher, Stephen J Sharp, Jian'an Luan and 22 more

2 registry-linked trialsOpen access · greenAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2017. 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 354 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
354citing papers in PubMed, 1 pooled it
36.0field-weighted citation impact, top 1% 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.

NCT04040595 nacompletednot on this mapstarted 2019, after this paper: background citation

The Genetics of Adipose Tissue Function and Its Link to Type 2 Diabetes and Heart Disease

TypeinterventionalSponsorRoyal Devon and Exeter NHS Foundation TrustRan2019 to 2021Enrolled207ConditionsDiabetes MellitusArmsAbdominal fat biopsy
NCT05459987 nacompletednot on this mapstarted 2022, after this paper: background citation

Feasibility and Impact of an Intensive Team-based Intervention on Prediabetes Remission in Patients With Coronary Heart Disease

TypeinterventionalSponsorMontreal Heart InstituteRan2022 to 2023Enrolled36ConditionsPrediabetic State, Coronary Heart Disease, Healthy Lifestyle, RemissionArmsLifestyle changes
3 · Its place in the literature

Who cites it

354 citing papers in PubMed, 1 synthesis or guideline pooled it, 601 citations in OpenAlex.

  1. Pooled it
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  9. Evaluating the therapeutic impact of tirzepatide in people with partial lipodystrophy.The Journal of clinical endocrinology and metabolism · 2026
    Observational
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  19. Biochemistry and biophysics reports · 2026
    Article
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294 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors at 10 institutions in 3 countries.

Luca A LottaMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Pawan GulatiMetabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Felix R DayMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Felicity PayneWellcome Trust Sanger Institute, Hinxton, UK.
Halit OngenDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Martijn van de BuntOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Kyle J GaultonDepartment of Pediatrics, University of California at San Diego, La Jolla, California, USA.
John D EicherPopulation Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
Stephen J SharpMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Jian'an LuanMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Emanuella De Lucia RolfeMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Isobel D StewartMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Eleanor WheelerWellcome Trust Sanger Institute, Hinxton, UK.
Sara M WillemsMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Claire AdamsMetabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Hanieh YaghootkarGenetics of Complex Traits, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Exeter, UK.
EPIC-InterAct Consortium
Cambridge FPLD1 Consortium
Nita G ForouhiMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Kay-Tee KhawDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Andrew D JohnsonPopulation Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
Robert K SempleMetabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Timothy FraylingGenetics of Complex Traits, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Exeter, UK.
John R B PerryMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Emmanouil DermitzakisDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Mark I McCarthyOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Inês BarrosoMetabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Nicholas J WarehamMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
David B SavageMetabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Claudia LangenbergMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Stephen O'RahillyMetabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Robert A ScottMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
University of Cambridge · GBMRC Epidemiology Unit · GBNational Heart Lung and Blood Institute · USOxford Centre for Diabetes, Endocrinology and Metabolism · GBUniversity of Geneva · CHWellcome/MRC Institute of Metabolic Science · GBWellcome Sanger Institute · GBRoyal Devon and Exeter Hospital · GBUniversity of California, San Diego · USUniversity of Exeter · GB

Funding

Cardiovascular Genomics and Bioinformatics projectsZIAHL006170 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI JOHNSON, ANDREW · 2013 to 2025
$25.3M
Cancer Research UK 14136Medical Research Council G0401527Medical Research Council G1000143Medical Research Council MC_PC_13046Medical Research Council MC_PC_13048Medical Research Council MC_QA137853Medical Research Council MC_UU_12012/5Medical Research Council MC_UU_12015/1Medical Research Council MR/L00002/1Medical Research Council MR/N003284/1Medical Research Council MR/N01104X/1Medical Research Council MR/N01104X/2Wellcome TrustWellcome Trust 090532Wellcome Trust 095515/Z/11/ZWellcome Trust 098381Wellcome Trust 100574/Z/12/ZWellcome Trust 107064Wellcome Trust WT098051
6 · The paper itself

Abstract

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

Indexed as

Adipose TissueAnimalsBlood GlucoseBody Mass IndexCardiovascular DiseasesCase-Control StudiesDisease Models, AnimalFemaleGenome-Wide Association StudyGenomicsHumansInsulin ResistanceMaleMetabolic DiseasesMiceObesityBlood Glucose

Identifiers

PMID27841877
PMCPMC5774584
OpenAlexW2551499720

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.