Evidence mapPaperPMID 42149139Full record

ReviewDiabetes2026

Growth Differentiation Factor-15 in Diabetic Kidney and Cardiovascular Disease: Pathogenic Driver or Protective Modulator.

Amani Slika, Maya Noureddine, Dalal Jomaa, Elie Emmanuel Abboud, Sarah Zaidan, Sami Azar, Fuad Ziyadeh, Rachel Njeim, Assaad A Eid

Abstract readReview
In one paragraph

Review in Diabetes, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

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

1 citing paper in PubMed.

  1. 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

9 authors.

Amani SlikaDepartment of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, and Medical Center, American University of Beirut, Beirut, Lebanon.
Maya NoureddineDepartment of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, and Medical Center, American University of Beirut, Beirut, Lebanon.
Dalal JomaaDepartment of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, and Medical Center, American University of Beirut, Beirut, Lebanon.
Elie Emmanuel AbboudDepartment of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, and Medical Center, American University of Beirut, Beirut, Lebanon.
Sarah ZaidanDepartment of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, and Medical Center, American University of Beirut, Beirut, Lebanon.
Sami AzarAUB Diabetes, Faculty of Medicine, and Medical Center, American University of Beirut, Beirut, Lebanon.
Fuad ZiyadehAUB Diabetes, Faculty of Medicine, and Medical Center, American University of Beirut, Beirut, Lebanon.
Rachel NjeimDepartment of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, and Medical Center, American University of Beirut, Beirut, Lebanon.
Assaad A EidDepartment of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, and Medical Center, American University of Beirut, Beirut, Lebanon.ORCID 0000-0002-3603-0960

Funding

American University of Beirut Biomedical Sciences graduate programAmerican University of Beirut Medical Practice Plan regular research grant
6 · The paper itself

Abstract

Diabetic kidney disease (DKD) and diabetic cardiomyopathy continue to drive excess morbidity and mortality in diabetes, underscoring a critical gap between mechanistic insight and clinical translation. Growth differentiation factor-15 (GDF-15), a stress-inducible cytokine of the transforming growth factor-β superfamily, has emerged as a critical biomarker and putative modulator of metabolic inflammation. Yet the field remains divided on a fundamental question: is GDF-15 simply reporting tissue distress, or does it shape disease trajectories? In this article, we explore how GDF-15 may both signal and shape DKD and cardiovascular disease. Drawing on evidence from experimental models, longitudinal clinical studies, and multi-omics analyses, we highlight the context-dependent biology of GDF-15, protective during acute metabolic or inflammatory stress but potentially pathogenic when chronically elevated in diabetes. We examine its regulation via the GFRAL-RET signaling axis, its segment-specific expression across renal tubular compartments, and its emerging role in cardiac remodeling and metabolic inflammation. Recent clinical data position circulating GDF-15 as an early and sensitive indicator of DKD progression and cardiovascular events. At the same time, mechanistic studies increasingly implicate sustained GDF-15 signaling in mitochondrial dysfunction, inflammatory amplification, and maladaptive tissue remodeling. Together, these observations place GDF-15 at a critical inflection point between risk stratification and disease mechanism. A key unresolved challenge is defining when, where, and how GDF-15 signaling exerts adaptive versus maladaptive effects-knowledge that will be essential for determining whether GDF-15 should be targeted, harnessed, or restrained in diabetes. ARTICLE HIGHLIGHTS: GDF-15 is a stress-responsive cytokine of the TGF-β superfamily regulated by p53, mitochondrial dysfunction, and inflammatory signaling. Circulating GDF-15 levels are low under physiological conditions but rise markedly in response to cellular and metabolic stress. Elevated GDF-15 predicts incident diabetes and reflects hyperglycemia-induced oxidative and cellular stress. GDF-15 correlates with albuminuria, estimated glomerular filtration rate decline, and progression risk in diabetic kidney disease. Increased levels predict heart failure, myocardial infarction, and cardiovascular mortality in diabetes. Targeting the GDF-15-GFRAL axis and leveraging GDF-15 as a biomarker offer emerging translational potential.

Indexed as

Cardiovascular DiseasesDiabetic CardiomyopathiesDiabetic NephropathiesGrowth Differentiation Factor 15AnimalsBiomarkersHumansSignal TransductionBiomarkersGDF15 protein, humanGrowth Differentiation Factor 15

Identifiers

PMID42149139
PMCPMC13291867

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.