Evidence map›Paper›PMID 40257392›Full record

ReviewAmerican journal of physiology. Heart and circulatory physiology2025

Metabolic and vascular insulin resistance: partners in the pathogenesis of cardiovascular disease in diabetes.

William B Horton, Kaitlin M Love, Justin M Gregory, Zhenqi Liu, Eugene J Barrett

Abstract readReview
In one paragraph

Review in American journal of physiology. Heart and circulatory physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
–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

58 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Observational
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Observational
  12. Review
  13. Article
  14. Article
  15. Article
  16. Observational
  17. Article
  18. Review
  19. Article
  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

5 authors.

William B HortonDivision of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, United States.ORCID 0000-0001-8081-1214
Kaitlin M LoveDivision of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, United States.ORCID 0000-0002-9352-393X
Justin M GregoryIan M. Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, Nashville, Tennessee, United States.
Zhenqi LiuDivision of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, United States.
Eugene J BarrettDivision of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, United States.ORCID 0000-0003-0689-4044

Funding

Role of Microvascular insulin resistance and cardiorespiratory fitness in diabetesR01DK124344 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI ZHENQI LIU, JUDITH G. REGENSTEINER · 2021 to 2026
$3.5M
Effects of Exercise and GLP-1R Agonism on Muscle Microvascular Perfusion and Insulin ActionR01DK125330 · NIDDK · UNIVERSITY OF VIRGINIA · PI LIU, ZHENQI · 2020 to 2025
$3.3M
Therapeutic Strategies for Microvascular Dysfunction in Type 1 DiabetesK23DK131327 · NIDDK · UNIVERSITY OF VIRGINIA · PI Kaitlin M Love · 2023 to 2026
$774k
American Heart Association (AHA) 941481Breakthrough T1D 3-SRA-2023-1236-M-BBreakthrough T1D 5-ECR-2020-950-A-NHHS | NIH | NIDDK | Division of Diabetes, Endocrinology, and Metabolic Diseases (DEM) K23DK131327HHS | NIH | NIDDK | Division of Diabetes, Endocrinology, and Metabolic Diseases (DEM) R01DK124344HHS | NIH | NIDDK | Division of Diabetes, Endocrinology, and Metabolic Diseases (DEM) R01DK125330NIDDK NIH HHS K23 DK131327NIDDK NIH HHS R01 DK124344NIDDK NIH HHS R01 DK125330
6 · The paper itself

Abstract

Vascular insulin resistance has emerged as a pivotal factor in the genesis of cardiovascular disease (CVD) in people with diabetes. It forms a complex pathogenic partnership with metabolic insulin resistance to significantly amplify the CVD risk of diabetes and other affected populations. Metabolic insulin resistance (characterized by quantitatively diminished insulin action on glucose metabolism in skeletal muscle, liver, and adipose tissue) is a hallmark of diabetes, obesity, and related conditions. In contrast, vascular insulin resistance is a less appreciated and not well-quantified complication of these conditions. Importantly, an impaired vascular response to insulin contributes directly to vascular dysfunction and over 40 years of research has convincingly shown that vascular and metabolic insulin resistance synergize to create an environment that predisposes individuals to CVD. In this review, we examine the multifaceted vascular actions of insulin, including its roles in regulating blood pressure, blood flow, endothelial health, and arterial stiffness. We also examine how these processes become disrupted in the setting of vascular insulin resistance, which subsequently undermines endothelial function, compromises tissue microvascular perfusion, and promotes vascular rigidity and atherosclerosis. We then highlight potential therapeutic strategies with demonstrated efficacy to improve vascular insulin sensitivity in people with diabetes and suggest that targeting disordered vascular insulin signaling holds promise not only for refining the functional understanding of vascular insulin resistance but also for developing innovative treatments with potential to reduce CVD risk and improve cardiovascular outcomes in people with diabetes.

Indexed as

Blood GlucoseCardiovascular DiseasesDiabetic AngiopathiesInsulinInsulin ResistanceAnimalsEndothelium, VascularHumansSignal TransductionVascular StiffnessBlood GlucoseInsulincardiovascular diseasesdiabetes mellitusendothelial cellsinsulin resistancemicrovessels

Identifiers

PMID40257392
PMCPMC12172477

What OpenQuestion holds

Textmetadata
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.