Evidence mapPaperPMID 21047922Full record

Trial reportThe Journal of clinical endocrinology and metabolism2011

Free fatty acids induce insulin resistance in both cardiac and skeletal muscle microvasculature in humans.

Jia Liu, Linda A Jahn, Dale E Fowler, Eugene J Barrett, Wenhong Cao, Zhenqi Liu

7 registry-linked trialsOpen access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 7 registered trials, which are not on this map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
21.4field-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.

NCT03355469 phase2 / phase3completedstarted 2017, after this paper: background citation

Exercise Dose and Metformin for Vascular Health in Adults With Metabolic Syndrome

Ran2017Enrolled91Registered outcomes6Posted comparisons36ConditionsMetabolic SyndromeArmsHigh intensity exercise, Low intensity exercise, Metformin, Placebo
Open the trial in the graph
NCT03883412 phase4recruitingstarted 2019, after this paper: background citation

Effect of Exercise and/or Liraglutide on Vascular Dysfunction and Insulin Sensitivity in Type 2 Diabetes ( ZQL007)

Ran2019Enrolled60Registered outcomes6Posted comparisons0ConditionsType2 DiabetesArmsExercise, liraglutide
Open the trial in the graph
NCT04203927 early_phase1unknown statusstarted 2020, after this paper: background citation

Effects of Empagliflozin on Cardiac Microvasculature and Insulin Sensitivity in Subjects With Type 2 Diabetes

Ran2020Enrolled50Registered outcomes4Posted comparisons0ConditionsInsulin Sensitivity, Type2 DiabetesArmsempagliflozin 25 mg
Open the trial in the graph
NCT04575844 phase4recruitingstarted 2020, after this paper: background citation

Effects of Exercise and GLP-1 Agonism on Muscle Microvascular Perfusion and Insulin Action in Adults With Metabolic Syndrome

Ran2020Enrolled80Registered outcomes6Posted comparisons0ConditionsMetabolic SyndromeArmsExercise Training, liraglutide, Liraglutide + Exercise training
Open the trial in the graph
NCT02490124 completednot on this mapstarted 2014, after this paper: background citation

The Effect of Type 1 Diabetes on Pan-Arterial Vascular Function and Insulin Sensitivity in Humans

TypeobservationalSponsorUniversity of VirginiaRan2014 to 2015Enrolled7ConditionsDiabetes Type 1
NCT03520569 early_phase1completednot on this mapstarted 2019, after this paper: background citation

Effect of Hyperglycemia on Microvascular Perfusion in Healthy Adults

TypeinterventionalSponsorUniversity of VirginiaRan2019 to 2021Enrolled15ConditionsVascular Stiffness, Insulin SensitivityArmsOctreotide, Insulin, Dextrose 20% solution
NCT04730882 completednot on this mapstarted 2021, after this paper: background citation

Effect of Postprandial Hyperglycemia on Vasculature in Type 1 Diabetes and Healthy Adults

TypeobservationalSponsorUniversity of VirginiaRan2021 to 2024Enrolled36ConditionsType 1 Diabetes, Hyperglycemia, PostprandialArmsMixed Meal
3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.

  1. Utility of Contrast-Enhanced Ultrasound for the Assessment of Skeletal Muscle Perfusion in Diabetes Mellitus: A Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2019
    Pooled it
  2. Trial
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  6. Differential effects of nebivolol vs. metoprolol on microvascular function in hypertensive humans.American journal of physiology. Heart and circulatory physiology · 2016
    Trial
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  10. Article
  11. Whole-bodyEuropean journal of nuclear medicine and molecular imaging · 2026
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Microvascular Skeletal-Muscle Crosstalk in Health and Disease.International journal of molecular sciences · 2023
    Review
  17. Article
  18. Review
  19. Review
  20. 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

6 authors at 2 institutions in 1 country.

Jia LiuDivision of Endocrinology and Metabolism, Department of Internal Medicine and General Clinical Research Center, University of Virginia Health System, P.O. Box 801410, Charlottesville, Virginia 22908, USA.
Linda A Jahn
Dale E Fowler
Eugene J Barrett
Wenhong Cao
Zhenqi Liu
University of Virginia Health System · USThe Hamner Institutes for Health Sciences · US

Funding

ZACOPRIDE VS METOCLOPRAMIDE--EFFECT ON LOWER ESOPHAGEAL SPHINCTERM01RR000847 · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · 1985 to 2005
$24.6M
THE EFFECTS OF INSULIN ON THE MICROVASCULATURER01DK057878 · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · 2001 to 2005
$1.5M
NCRR NIH HHS M01 RR000847NCRR NIH HHS RR-00847NHLBI NIH HHS R01 HL094722NHLBI NIH HHS R01HL094722NIDDK NIH HHS R01 DK057878NIDDK NIH HHS R01DK057878NIDDK NIH HHS R01 DK073759NIDDK NIH HHS R01DK073759
6 · The paper itself

Abstract

contextInsulin recruits microvasculature in both cardiac and skeletal muscle, which increases the endothelial exchange surface area. Plasma concentrations of free fatty acids (FFAs) are elevated in patients with diabetes, which impairs insulin-mediated skeletal muscle microvascular recruitment.

objectiveThe objective of the study was to examine whether elevated FFAs likewise cause insulin resistance in cardiac muscle microvasculature.

settingThe study was conducted at the General Clinical Research Center at the University of Virginia.

methodsTwenty-two healthy, young adults were studied twice in random order after an overnight fast. Each subject received a 5-h systemic infusion of either saline or Intralipid/heparin with a 1 mU/min · kg euglycemic insulin clamp superimposed for the last 2 h. Cardiac and forearm skeletal muscle microvascular blood volume (MBV) and flow velocity were measured and microvascular blood flow (MBF) calculated before and at the end of the insulin infusion.

resultsInsulin significantly increased MBV and MBF in both cardiac (P < 0.0001 for both) and skeletal (P = 0.008 and < 0.03, respectively) muscle. Microvascular flow velocity increased slightly but significantly in the skeletal (P = 0.04) but not in cardiac muscle. Lipid infusion lowered insulin-stimulated whole-body glucose disposal and abolished insulin-mediated increases in MBV and MBF in both cardiac and skeletal muscle. Whole-body insulin sensitivity predicted skeletal but not cardiac muscle microvascular responses to insulin. Insulin even decreased skeletal muscle MBV during lipid infusion in subjects who were moderately sensitive to insulin metabolically.

conclusionsIn conclusion, high plasma concentrations of FFAs cause insulin resistance in cardiac as well as skeletal muscle microvasculature in healthy humans. This may contribute to the association of cardiac complications with metabolic insulin resistance in diabetes.

Indexed as

MyocardiumAdultBlood PressureCapillariesFat Emulsions, IntravenousFatty Acids, NonesterifiedFemaleForearmHeartHumansHyperinsulinismHypoglycemic AgentsInsulinInsulin ResistanceLipidsMaleFat Emulsions, IntravenousFatty Acids, NonesterifiedHypoglycemic AgentsInsulinLipids

Identifiers

PMID21047922
PMCPMC3048322
OpenAlexW1990190556

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

and 1 more above

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.