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Record W4399684210 · doi:10.2337/db24-755-p

755-P: GLP-1RA Therapy Recovers Vascular Regenerative Cell Content in High Cardiovascular–Risk Individuals with Type 2 Diabetes

2024· article· en· W4399684210 on OpenAlexaboutno aff
Aishwarya Krishnaraj, Brady Park, Ehab Bakbak, Raj Verma, Adrian Quan, Hwee Teoh, David A. Hess, Subodh Verma

Bibliographic record

VenueDiabetes · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAngiogenesis and VEGF in Cancer
Canadian institutionsnot available
Fundersnot available
KeywordsProgenitor cellFlow cytometryType 2 diabetesCell therapyMedicineCohortInternal medicineDiabetes mellitusCellGastroenterologyStem cellImmunologyEndocrinologyBiologyBiochemistryCell biology

Abstract

fetched live from OpenAlex

Objective: GLP-1RAs are recommended as first-line therapy for cardiorenal risk reduction in people with T2D. We have shown that SGLT2 inhibitor therapy increased circulating vascular regenerative (VR) cell content in individuals with T2D. The ORIGINS-RCE trial recently reported that VR cell content was decreased in South Asian (SA) individuals compared to people of White European (WE) origin. This sub-analysis sought to determine the impact of GLP-1RA and SGLT2 inhibitor therapy on VR cell content in SA vs. WE individuals with T2D. Methods: ORIGINS-RCE enrolled 120 individuals of SA or WE ethnicity with T2D and/or CVD. Within this cohort, 88 had T2D amongst whom 22 were on a GLP-1RA, 39 on an SGLT2 inhibitor, and 27 on neither. Multi-parametric flow cytometry was used to enumerate pro-vascular vs. pro-inflammatory progenitor cell subsets. Results: The absolute count of VR cells (ALDHhiSSClowCD133+ cells/106 MNC) in the GLP-1RA group (310 ±56) was similar to that in the SGLT2 inhibitor group (244 ± 23; P=0.32), but greater than that in the neither therapy group (216 ± 33; P=0.027). The GLP-1RA group also had greater endothelial progenitor cell content (ALDHhiSSClowCD34+CD45-CD133+; 11 ± 3) compared to the neither therapy group (7 ± 2; P=0.011). The pro-inflammatory burden of ALDHhiSSChi precursor cells in the GLP-1RA group (41845 ± 12616) was lower than that of the neither therapy (53900 ± 7249; P=0.015). While there was no difference in ALDHhiSSClowCD133+ content between WE and SA individuals within the GLP-1RA and neither therapy groups, there were less of these cells among the SA (vs. WE) individuals in the SGLT2 inhibitor group (202 ±28 vs. 318 ± 31; P=0.010), suggesting a lack of a protective response of SGLT2 inhibitor therapy in SA people. Conclusion: In individuals with T2D, VR progenitor cell content varied according to medication use and ethnic origin. These data uncovered conserved cardioprotective benefits of GLP-1RA therapy in high-risk SA individuals. Disclosure A. Krishnaraj: None. B. Park: None. E. Bakbak: None. R. Verma: None. A. Quan: None. H. Teoh: Other Relationship; Canadian Medical and Surgical Knowledge Translation Research Group. D.A. Hess: None. S. Verma: Other Relationship; Amarin Corporation, Amgen Inc., AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novartis AG, Novo Nordisk, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., S&L Solutions Event Management, Sanofi. Funding CIHR (#369189 and #186065); Heart and Stroke Foundation (#G-23-0035127)

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.214
Teacher spread0.201 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2024
Admission routes1
Has abstractyes

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