Evidence mapPaperPMID 33570554Full record

ReviewThe Journal of clinical endocrinology and metabolism2021

DPP4 Activity, Hyperinsulinemia, and Atherosclerosis.

Kaitlin M Love, Zhenqi Liu

Open access · bronzeAbstract readReview
In one paragraph

Review in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
5.4field-weighted citation impact, top 3% 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.

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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Impact of DPP-4 Inhibitors on Interleukin Levels in Type 2 Diabetes Mellitus.The Journal of clinical endocrinology and metabolism · 2025
    Pooled it
  2. Neurovascular Actions of Dipeptidyl Peptidase-4 Inhibitors and Their Implications for Cognitive Dysfunction in Type 2 Diabetes Mellitus.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026
    Review
  3. Exploring Active Ingredients and Mechanisms ofMolecules (Basel, Switzerland) · 2026
    Article
  4. CD8Nature reviews. Cardiology · 2026
    Review
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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

2 authors at 1 institution in 1 country.

Kaitlin M LoveDivision of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
Zhenqi LiuDivision of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.ORCID 0000-0001-5077-0941
University of Virginia Health System · US

Funding

The integrated Translational Health Research Institute of Virginia (iTHRIV): Using Data to Improve HealthUL1TR003015 · NCATS · UNIVERSITY OF VIRGINIA · PI Donald E Brown, KAREN C. JOHNSTON · 2022 to 2023
$9.1M
Institutional Career Development CoreKL2TR003016 · NCATS · UNIVERSITY OF VIRGINIA · PI Jason Papin, BRADFORD B WORRALL · 2022 to 2023
$2.1M
Role of Microvascular insulin resistance and cardiorespiratory fitness in diabetesR01DK124344 · NIDDK · UNIVERSITY OF COLORADO DENVER · 2023 to 2025
$1.4M
Effects of Exercise and GLP-1R Agonism on Muscle Microvascular Perfusion and Insulin ActionR01DK125330 · UNIVERSITY OF VIRGINIA · 2025 to 2025
$657k
Interdisciplinary Training in Systems & Biomolecular Data ScienceT32GM145443 · UNIVERSITY OF VIRGINIA · 2025 to 2025
$321k
NCATS NIH HHS KL2 TR003016NCATS NIH HHS UL1 TR003015NIDDK NIH HHS F32 DK121431NIDDK NIH HHS R01 DK102359NIDDK NIH HHS R01 DK124344NIDDK NIH HHS R01 DK125330NIGMS NIH HHS T32 GM145443
6 · The paper itself

Abstract

contextObesity and type 2 diabetes are associated with chronic hyperinsulinemia, elevated plasma levels of dipeptidyl peptidase-4 (DPP4), and a pro-atherosclerotic milieu. EVIDENCE ACQUISITION: PubMed search of the term "insulin and atherosclerosis," "hyperinsulinemia," "atherosclerosis," or "cardiovascular outcomes" cross-referenced with "DPP4." Relevant research and review articles were reviewed. EVIDENCE SYNTHESIS: Hyperinsulinemia in the setting of insulin resistance promotes vascular inflammation, vascular smooth muscle cell growth, pathological cholesterol profile, hypertension, and recruitment of immune cells to the endothelium, all contributing to atherosclerosis. DPP4 has pleiotropic functions and its activity is elevated in obese humans. DPP4 mirrors hyperinsulinemia's atherogenic actions in the insulin resistant state, and genetic deletion of DPP4 protects rodents from developing insulin resistance and improves cardiovascular outcomes. DPP4 inhibition in pro-atherosclerotic preclinical models results in reduced inflammation and oxidative stress, improved endothelial function, and decreased atherosclerosis. Increased incretin levels may have contributed to but do not completely account for these benefits. Small clinical studies with DPP4 inhibitors demonstrate reduced carotid intimal thickening, improved endothelial function, and reduced arterial stiffness. To date, this has not been translated to cardiovascular risk reduction for individuals with type 2 diabetes with prior or exaggerated risk of cardiovascular disease.

conclusionDPP4 may represent a key link between central obesity, insulin resistance, and atherosclerosis. The gaps in knowledge in DPP4 function and discrepancy in cardiovascular outcomes observed in preclinical and large-scale randomized controlled studies with DPP4 inhibitors warrant additional research.

Indexed as

AnimalsAtherosclerosisCardiovascular DiseasesDipeptidyl Peptidase 4HumansHyperinsulinismInsulin ResistanceOxidative StressDipeptidyl Peptidase 4DPP4 protein, humanatherosclerosisdiabetesDPP4hyperinsulinemiainsulin resistanceoxidative stress

Identifiers

PMID33570554
PMCPMC8118363
OpenAlexW3126248919

What Socratic holds

Textmetadata
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 Socratic graph.