Evidence map›Paper›PMID 41408588›Full record

ArticleCardiovascular diabetology. Endocrinology reports2025

Altered RBC aggregability in diabetes: a threshold for pathophysiological structure-function RBC changes.

Ifechukwude Ebenuwa, Pierre-Christian Violet, Stephanie Teng, Thom Greene, Nicholas Munyan, Razi Berman, Irene Rozga, Mary Walter, Kenneth J Wilkins, Nermi Parrow and 1 more

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Article in Cardiovascular diabetology. Endocrinology reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Ifechukwude EbenuwaDigestive Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bldg. 10 Room 4D51, Bethesda, MD, 20892, USA. Ebenuwaic@nih.gov.
Pierre-Christian VioletDigestive Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bldg. 10 Room 4D51, Bethesda, MD, 20892, USA.
Stephanie TengDigestive Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bldg. 10 Room 4D51, Bethesda, MD, 20892, USA.
Thom GreeneDigestive Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bldg. 10 Room 4D51, Bethesda, MD, 20892, USA.
Nicholas MunyanDigestive Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bldg. 10 Room 4D51, Bethesda, MD, 20892, USA.
Razi BermanDigestive Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bldg. 10 Room 4D51, Bethesda, MD, 20892, USA.
Irene RozgaDigestive Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bldg. 10 Room 4D51, Bethesda, MD, 20892, USA.
Mary WalterClinical Laboratory Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Kenneth J WilkinsBiostatistics Program, Office of Clinical Research Support, Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Nermi ParrowDigestive Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bldg. 10 Room 4D51, Bethesda, MD, 20892, USA.
Mark LevineDigestive Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bldg. 10 Room 4D51, Bethesda, MD, 20892, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveVascular complications have been associated with pathophysiological RBC changes including reduced RBC deformability (RBCD): the ability of RBCs to change their shape in the microvasculature and increased red blood cell aggregability (RBCA): the tendency of RBCs to form aggregates (rouleaux). However, understanding of aberrant RBCA in diabetes and its relationship with RBCD is limited. We investigated clinical and RBC structural and functional changes associated with RBCA in comparison with RBCD.

methodsWe conducted an outpatient cross-sectional study of participants with diabetes (n = 81) and nondiabetic controls (n = 78) at the National Institutes of Health. Clinical history was obtained using standardized forms, fasting blood and urine samples were collected for clinical laboratory measurements and ektacytometry studies of RBC physiological parameters: RBCA, RBCD and osmotic fragility. Functional RBC changes were assessed using hemoglobin-oxygen dissociation (p50). Major outcomes assessed differences in RBCA Aggregation Index (AI), with increased RBCA defined as higher AI. Exploratory outcomes assessed differences in subgroups with type 1 (T1D) and type 2 (T2D) diabetes, and associations with clinical, inflammatory, endocrine and RBC physiological parameters. Outcomes were assessed using both nonparametric and multivariable regression methods.

resultsCompared with controls, AI was significantly higher in the diabetes cohort (75±8 vs 71 ± 11, p = 0.007), T2D (77±7 vs 71 ± 11, p < 0.001), but not T1D (69±7 vs 71 ± 11, p = 0.242). While RBCD values were similar in T1D and T2D (p = 0.31), mean AI value was significantly higher in T2D vs T1D (p = 0.02). In contrast to RBCD, AI was associated with T2D (p < 0.001), BMI (p < 0.001), insulin resistance (HOMA-IR, p = 0.033), leptin (p < 0.001), C-peptide levels (p = 0.009), but not vascular complications (p = 0.156). While RBCA and RBCD were associated with CRP (p < 0.001 and p = 0.005 respectively), neither was associated with fibrinogen (p = 0.768 and p = 0.118 respectively). In contrast to RBCD, AI was associated with increased osmotic fragility (p < 0.001) and a threshold of altered hemoglobin-oxygen dissociation (p50) estimated at AI of 75 in both groups using piecewise linear statistical modeling. Thus, AI was positively correlated with p50 at AI < 75 (p = 0.033) and negatively correlated at AI ≥ 75 (p = 0.007).

conclusionsFindings show that in contrast to RBCD, RBCA is characterized by a RBC functional threshold beyond which oxygen release is reduced, and RBC structure-function relationship likely modulated by insulin resistance and pro-inflammatory endocrine factors. The distinct but complementary and synergistic changes in RBCD and RBCA provide a framework for strategies aimed at mitigation of vascular risk in diabetes.

Indexed as

DeformabilityDiabetesHemoglobin-oxygen dissociationOsmotic fragilityRBC aggregabilityRBC structure-functionVascular complications

Identifiers

PMID41408588
PMCPMC12713270

What Socratic holds

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LicenceCC BY
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Registered trials

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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.