Evidence mapPaperPMID 39503770Full record

Trial reportDiabetologia2025

Microvascular insulin resistance with enhanced muscle glucose disposal in CD36 deficiency.

Cyndya A Shibao, Vivek S Peche, Terri A Pietka, Dmitri Samovski, Ian M Williams, Naji N Abumrad, Eric R Gamazon, Ira J Goldberg, David H Wasserman, Nada A Abumrad

Registry-linked trialAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03012386 (Role of CD36 in Nutrient Delivery and Its Dysfunction in African Americans), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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.

NCT03012386 phase1 / phase2completednot on this map

Role of CD36 in Nutrient Delivery and Its Dysfunction in African Americans

TypeinterventionalSponsorVanderbilt University Medical CenterRan2017 to 2021Enrolled26ConditionsInsulin Resistance, Endothelial DysfunctionArmsSildenafil Citrate in G allele carrier, Sildenafil Citrate in non G allele carrier
3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Endothelial Cell Regulation of Lipid Uptake During Feeding and Fasting.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  2. Insulin Resistance and Inflammation.International journal of molecular sciences · 2026
    Review
  3. Review
  4. Review
  5. Review
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Cyndya A ShibaoDepartment of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA. cyndya.shibao@vumc.org.
Vivek S PecheDepartment of Medicine, Division of Nutritional Sciences and Obesity Research, Washington University School of Medicine, St Louis, MO, USA.
Terri A PietkaDepartment of Medicine, Division of Nutritional Sciences and Obesity Research, Washington University School of Medicine, St Louis, MO, USA.
Dmitri SamovskiDepartment of Medicine, Division of Nutritional Sciences and Obesity Research, Washington University School of Medicine, St Louis, MO, USA.
Ian M WilliamsDepartment of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA.
Naji N AbumradDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
Eric R GamazonDepartment of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, USA.
Ira J GoldbergDepartment of Medicine, Division of Endocrinology, Diabetes and Metabolism, New York University Grossman School of Medicine, New York, NY, USA.
David H WassermanDepartment of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA.
Nada A AbumradDepartment of Medicine, Division of Nutritional Sciences and Obesity Research, Washington University School of Medicine, St Louis, MO, USA. nabumrad@wustl.edu.

Funding

Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR002243 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2025 to 2025
$10.7M
Washington University Nutrition Obesity Research CenterP30DK056341 · WASHINGTON UNIVERSITY · 1999 to 2025
$5.7M
WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · 2022 to 2025
$5.6M
Pathways of Tissue Lipid UptakeR01HL045095 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Nada A. Abumrad, Ira J Goldberg · 1991 to 2024
$2.3M
NCATS NIH HHS 5UL1TR002243NCATS NIH HHS UL1 TR002243NHLBI NIH HHS R01HL045095NHLBI NIH HHS R01 HL157584NHLBI NIH HHS R01HL157584NIDDK NIH HHS P30 DK056341NIDDK NIH HHS R01 DK111175NIDDK NIH HHS R01DK111175
6 · The paper itself

Abstract

aims/hypothesisMicrovascular dysfunction contributes to insulin resistance. CD36, a fatty acid transporter and modulator of insulin signalling, is abundant in microvascular endothelial cells. Humans carrying the minor allele (G) of CD36 coding variant rs3211938 have 50% reduced CD36 expression and show endothelial dysfunction. We aimed to determine whether G allele carriers have microvascular resistance to insulin and, if so, how this affects glucose disposal.

methodsOur multi-disciplinary approach included hyperinsulinaemic-euglycaemic clamps in Cd36

resultsInsulin clamps showed that Cd36 CONCLUSIONS/

interpretationCD36 deficiency was previously shown to reduce muscle/heart fatty acid uptake, whereas here we showed that it reduced vascular compliance and the ability of insulin to increase MBV for optimising glucose and oxygen delivery. The muscle and heart respond to these energy challenges by transcriptional remodelling priming the tissue for insulin-stimulated glycolytic flux. Reduced oxygen delivery activating hypoxia-induced factors, endothelial release of growth factors or small intracellular vesicles might mediate this adaptation. Targeting NO bioavailability in CD36 deficiency could benefit the microvasculature and muscle/heart metabolism.

trial registrationClinicaltrials.gov NCT03012386 DATA AVAILABILITY: The RNAseq data generated in this study have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/ ) under accession code GSE235988 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE235988 ).

Indexed as

CD36 AntigensGlucoseInsulin ResistanceMicrovesselsMuscle, SkeletalAdultAnimalsEndothelial CellsFemaleGlucose Clamp TechniqueHumansInsulinMaleMiceMice, Inbred C57BLMice, KnockoutCD36 AntigensGlucoseInsulinAfrican AmericansCaveolinEndothelial functionNitric oxiders3211938

Identifiers

PMID39503770
PMCPMC11832635

What Socratic holds

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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.