# Association of serum methylglyoxal with endothelial dysfunction in patients with type 2 diabetes

**Authors:** Shanshan Yu, Xinyan Jin, Yuanying Xu, Zhao Liu, Jun Lu, Jie Gao, Wenjun Sha, Tao Lei

PMC · DOI: 10.3389/fphar.2026.1773149 · Frontiers in Pharmacology · 2026-02-04

## TL;DR

This study shows that higher levels of methylglyoxal in the blood are linked to worse blood vessel function in people with type 2 diabetes, suggesting it could be a useful early warning sign.

## Contribution

The study identifies serum methylglyoxal as an independent and clinically relevant biomarker for endothelial dysfunction in type 2 diabetes.

## Key findings

- Higher serum methylglyoxal levels were significantly associated with endothelial dysfunction in 76% of type 2 diabetes patients.
- Methylglyoxal showed a strong negative correlation with flow-mediated dilation, even after adjusting for age and sex.
- Methylglyoxal demonstrated good predictive power with an AUC of 0.785 for identifying endothelial dysfunction.

## Abstract

To explore the correlation between serum Methylglyoxal (MGO) and endothelial dysfunction in patients with type 2 diabetes mellitus, and to evaluate the clinical value of MGO in the development of diabetes mellitus and its complications.

In this cross-sectional study, we enrolled 250 patients diagnosed with T2MD. Based on flow-mediated dilation (FMD) measurements, the patients were categorized into normal endothelial function group (FMD ≥6.4%, n = 61) and endothelial dysfunction group (FMD <6.4%, n = 189). Analysis of the relationship between MGO and FMD was conducted via Spearman’s correlation, partial correlation, and multiple logistic regression. An ROC curve analysis was utilized to quantify the predictive performance of MGO for endothelial function.

Endothelial dysfunction was observed in 189 (76%) patients with type 2 diabetes. Patients with endothelial dysfunction had higher concentration of MGO in the serum (P < 0.001) than those without endothelial dysfunction. Spearman correlation analysis showed that there was a significantly negative correlation between FMD and MGO (R = −0.611, p < 0.001), and this negative correlation remained significant upon adjustment for age and sex. (R = −0.36, p < 0.001). Logistic regression analysis identified MGO as an independent risk factor for endothelial dysfunction (OR 1.099, (1.06–1.14), p < 0.001), and the odds of endothelial dysfunction increased 2.67-fold per standard deviation (SD) increment in MGO levels (OR: 2.67 (1.78–4.01), p < 0.001) (Model 1). After adjusting for gender, age, BMI, course of disease, hypertension, smoking and alcohol consumption (model 2) as well as HbA1c, HOMA-IR, C-reactive protein and TG (model 3), similar results were obtained. Restricted cubic spline (RCS) analysis revealed a significant non-linear does-response relationship between MGO levels and endothelial function (P
overall<0.001, P
non-linearing<0.001). Subgroup analyses demonstrated that the association between MGO levels and endothelial function remained consistent across various strata, including age, sex, and comoribidities (all P
interaction>0.05). Receiver operating characteristic (ROC) curve: the area of under the ROC curve (AUC) for MGO was 0.785 (OR: 0.73-0.84, p < 0.001).

MGO was significantly inversely associated with FMD and endothelial function in T2DM patients, and can be used as a biomarker to assess vascular endothelial health. Detection of serum MGO levels has clinical significance in the prevention of early diabetic vascular disease.

## Linked entities

- **Chemicals:** methylglyoxal (PubChem CID 880)
- **Diseases:** type 2 diabetes mellitus (MONDO:0005148)

## Full-text entities

- **Genes:** FSHMD1A (facioscapulohumeral muscular dystrophy 1A) [NCBI Gene 2489] {aka FMD, FSHD, FSHD1A, FSHMD}, EDN1 (endothelin 1) [NCBI Gene 1906] {aka ARCND3, ET1, HDLCQ7, PPET1, QME}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}
- **Diseases:** metabolic disease (MESH:D008659), autoimmune diseases (MESH:D001327), obesity (MESH:D009765), diabetic angiopathy (MESH:D003925), polyphagia (MESH:D006963), overweight (MESH:D050177), psychiatric disorders (MESH:D001523), decline of endothelial function (MESH:D060825), liver and kidney dysfunction (MESH:D051437), Endothelial Dysfunction (MESH:D014652), Diabetes (MESH:D003920), malignant tumors (MESH:D009369), polyuria (MESH:D011141), trauma (MESH:D014947), inflammation (MESH:D007249), complications (MESH:D008107), phosphotriose isomerase deficiency (MESH:C566029), Hyperglycemia (MESH:D006943), dyslipidemia (MESH:D050171), Acute coronary syndrome (MESH:D054058), necrotic (MESH:D009336), cognitive dysfunction (MESH:D003072), endothelial (MESH:D005642), Type 2 diabetes (MESH:D003924), diabetic ketoacidosis (MESH:D016883), dysfunction (MESH:D006331), cardiovascular and cerebrovascular diseases (MESH:D002318), infection (MESH:D007239), polydipsia (MESH:D059606), weight loss (MESH:D015431), ACS (MESH:D000168), Insulin Resistance (MESH:D007333), anemia (MESH:D000740), macrovascular and microvascular diseases (MESH:D017566), hypertension (MESH:D006973), death (MESH:D003643), diabetic complications (MESH:D048909), Atherosclerosis (MESH:D050197)
- **Chemicals:** C-Peptide (MESH:D002096), cholesterol (MESH:D002784), nitric oxide (MESH:D009569), F (MESH:D005461), free fatty acids (MESH:D005230), Triglyceride (MESH:D014280), acid (MESH:D000143), sugars (MESH:D000073893), TC (MESH:D013667), INS (MESH:D007204), lysine (MESH:D008239), alcohol (MESH:D000438), glucose (MESH:D005947), ROS (MESH:D017382), MGO (MESH:D011765), glutathione (MESH:D005978), peroxynitrite (MESH:D030421), lipid (MESH:D008055), arginine (MESH:D001120), FCP (-), NO (MESH:D009614), TG (MESH:D013866), caffeine (MESH:D002110)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** C-25  C

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## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC12913059/full.md

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Source: https://tomesphere.com/paper/PMC12913059