Evidence map›Paper›PMID 37005603›Full record

ArticleDiabetology & metabolic syndrome2023

Does hyperglycemia affect arginine metabolites in critically ill patients? A prospective cohort and in vitro study.

Tien F Lee, Sara Tommasi, Andrew Bersten, Leonie K Heilbronn, Salvatore Sotgia, Angelo Zinellu, Ciriaco Carru, Arduino A Mangoni, Morton G Burt

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetology & metabolic syndrome, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 26% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Mechanisms of Homoarginine: Looking Beyond Clinical Outcomes.Acta physiologica (Oxford, England) · 2025
    Review
  3. Article
  4. 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 at 4 institutions in 2 countries.

Tien F LeeCollege of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, SA, 5042, Australia.
Sara TommasiCollege of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, SA, 5042, Australia.
Andrew BerstenCollege of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, SA, 5042, Australia.
Leonie K HeilbronnFaculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia.
Salvatore SotgiaDepartment of Biomedical Sciences, School of Medicine, University of Sassari, Sassari, Italy.
Angelo ZinelluDepartment of Biomedical Sciences, School of Medicine, University of Sassari, Sassari, Italy.
Ciriaco CarruDepartment of Biomedical Sciences, School of Medicine, University of Sassari, Sassari, Italy.
Arduino A MangoniCollege of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, SA, 5042, Australia.
Morton G BurtCollege of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, SA, 5042, Australia. morton.burt@sa.gov.au.
Flinders University · AUUniversity of Sassari · ITFlinders Medical Centre · AUThe University of Adelaide · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChanges in the arginine metabolites asymmetric dimethyl-L-arginine (ADMA) and L-homoarginine and acute blood glucose concentrations have been shown to cause endothelial dysfunction and be independently associated with mortality in Intensive Care Unit (ICU) patients. The aim of this study was to investigate whether hyperglycemia potentially modulates these arginine metabolite concentrations to provide a mechanism that may link hyperglycemia and mortality in this patient group.

methodsA clinical and in vitro study were undertaken. Glucose, glycosylated hemoglobin-A1c (HbA1c) and the stress hyperglycemia ratio (SHR) (to quantify absolute, chronic and relative hyperglycemia respectively) were measured in 1155 acutely unwell adult patients admitted to a mixed medical-surgical ICU. SHR was calculated by dividing the admission glucose by the estimated average glucose over the last 3 months, which was derived from HbA1c. ADMA and L-homoarginine were measured in a plasma sample collected at admission to ICU by liquid chromatography tandem mass spectrometry. The activity of dimethylarginine-dimethylaminohydrolase 1 (DDAH1), the main enzyme regulating ADMA concentrations, was assessed at varying glucose concentrations in vitro by quantifying the conversion of ADMA to citrulline in HEK293 cells that overexpress DDAH1.

resultsIn the clinical study, plasma ADMA was not significantly associated with any measure of hyperglycemia. L-homoarginine was positively associated with glucose (β = 0.067, p = 0.018) and SHR (β = 0.107, p < 0.001) after correction for glomerular filtration rate. However, as L-homoarginine is a negative predictor of mortality, the direction of these associations are the opposite of those expected if hyperglycemia was affecting mortality via changes in L-homoarginine. In vitro DDAH1 activity was not significantly influenced by glucose concentrations (p = 0.506).

conclusionIn critically ill patients the association between relative hyperglycemia and mortality is not mediated by changes in ADMA or L-homoarginine. Trial registration ANZCTR Trial ID ACTRN12615001164583.

Indexed as

Asymmetric dimethyl-L-arginineCritical illnessDimethylarginine-dimethylaminohydrolase 1Endothelial functionL-homoarginineStress hyperglycemia ratio

Identifiers

PMID37005603
PMCPMC10067243
OpenAlexW4362507085

What Socratic holds

Textmetadata
LicenceCC BY
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.