The CML/esRAGE ratio as a potential biomarker of early diastolic impairment in asymptomatic type 1 diabetic patients without overt heart disease.
- 1Department of Cardiology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515000, China. [email protected].
- 2Department of Ultrasound, Shantou Central Hospital, Shantou, Guangdong, 515000, China.
- 3Department of Endocrinology and Rheumatology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515000, China.
Abstract
Background
Heart failure is a prevalent complication of diabetic microangiopathy, and early identification of myocardial dysfuntion is crucial. Advanced glycation end products (AGEs) bind to their receptor RAGE and further promote diabetic late complications as well as heart failure. Two soluble RAGE isoforms, endogenous secretory RAGE (esRAGE) and the cleaved extracellular fragment of membrane RAGE (collectively termed sRAGE), are believed to exert cardioprotective effects by acting as RAGE decoy receptors. This pilot study aimed to investigate the associations of AGEs, sRAGE and esRAGE with early cardiac dysfunction identified via advanced echocardiography.Methods
We enrolled 29 type 1 diabetic patients without known heart disease(EF ≥ 50%) and 31 healthy controls. Plasma levels of two major AGEs, carboxymethyllysine(CML) and methylglyoxal-derived hydroimidazolone 1(MG-H1), as well as sRAGE and esRAGE were measured using immunoassay. Conventional, tissue Doppler, and speckle-tracking echocardiography were performed.Results
In the diabetic group, global longitudinal strain (GLS) and peak early diastolic velocity at the lateral mitral annulus [e(lat)] were significantly lower, while E/e(lat) was higher. CML levels and CML/esRAGE ratio were increased, and esRAGE was decreased in the diabetic group. Pearson correlation analysis showed GLS was significantly associated with disease duration, total cholesterol (TC), HbA1c, esRAGE, and CML/esRAGE ratio; Univariate linear regression confirmed that higher CML/esRAGE ratio was associated with lower e(lat) (β = -0.006, P = 0.047).Variables with P < 0.1 in univariate regression together with pre-specified clinical covariates including age, gender, HbA1c, disease duration, and heart rate were incorporated into stepwise multiple regression; the model demonstrated that CML/esRAGE was independently associated with e(lat) (β = -0.006, 95%CI: [-0.012, -0.001], P = 0.049).Conclusion
Elevated CML/esRAGE ratio is associated with impaired left ventricular diastolic function, and may represent a candidate biomarker for early diastolic dysfunction. Our study also suggest that CML/esRAGE ratio may not associated with GLS abnormalities reflecting subclinical systolic dysfunction. All observations from this pilot study require further validation in large independent prospective cohorts.
Related
- Moesin emerges as a potential exploratory biomarker associated with renal fibrosis in diabetic kidney disease
- Exploring systemic erythropoietin in diabetic retinopathy: Longitudinal associations and biomarker potential in the LANDMark cohort
- Revascularization in Asymptomatic Carotid Artery Stenosis With Hemodynamic Impairment and Cognitive Outcomes
- Combined vitamins C and E attenuate memory impairment and hippocampal damage in diabetic sleep-deprived mice: behavioral and molecular insights
- Association of conventional and non-conventional lipid profile with cognitive impairment among type 2 diabetic patients
BibTeX
@article{wang2026cmlesrage,
title = {{The CML/esRAGE ratio as a potential biomarker of early diastolic impairment in asymptomatic type 1 diabetic patients without overt heart disease.}},
author = {Daiming Wang and Jing Lin and Shiyi Chen},
journal = {BMC cardiovascular disorders},
year = {2026},
month = jul,
doi = {10.1186/s12872-026-06361-z},
url = {https://europepmc.org/article/MED/42902164},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - The CML/esRAGE ratio as a potential biomarker of early diastolic impairment in asymptomatic type 1 diabetic patients without overt heart disease.
AU - Daiming Wang
AU - Jing Lin
AU - Shiyi Chen
PY - 2026
DA - 2026/07/01
JO - BMC cardiovascular disorders
DO - 10.1186/s12872-026-06361-z
UR - https://europepmc.org/article/MED/42902164
AB - Background Heart failure is a prevalent complication of diabetic microangiopathy, and early identification of myocardial dysfuntion is crucial. Advanced glycation end products (AGEs) bind to their receptor RAGE and further promote diabetic late complications as well as heart failure. Two soluble RAGE isoforms, endogenous secretory RAGE (esRAGE) and the cleaved extracellular fragment of membrane RAGE (collectively termed sRAGE), are believed to exert cardioprotective effects by acting as RAGE decoy receptors. This pilot study aimed to investigate the associations of AGEs, sRAGE and esRAGE with early cardiac dysfunction identified via advanced echocardiography.Methods We enrolled 29 type 1 diabetic patients without known heart disease(EF ≥ 50%) and 31 healthy controls. Plasma levels of two major AGEs, carboxymethyllysine(CML) and methylglyoxal-derived hydroimidazolone 1(MG-H1), as well as sRAGE and esRAGE were measured using immunoassay. Conventional, tissue Doppler, and speckle-tracking echocardiography were performed.Results In the diabetic group, global longitudinal strain (GLS) and peak early diastolic velocity at the lateral mitral annulus [e(lat)] were significantly lower, while E/e(lat) was higher. CML levels and CML/esRAGE ratio were increased, and esRAGE was decreased in the diabetic group. Pearson correlation analysis showed GLS was significantly associated with disease duration, total cholesterol (TC), HbA1c, esRAGE, and CML/esRAGE ratio; Univariate linear regression confirmed that higher CML/esRAGE ratio was associated with lower e(lat) (β = -0.006, P = 0.047).Variables with P < 0.1 in univariate regression together with pre-specified clinical covariates including age, gender, HbA1c, disease duration, and heart rate were incorporated into stepwise multiple regression; the model demonstrated that CML/esRAGE was independently associated with e(lat) (β = -0.006, 95%CI: [-0.012, -0.001], P = 0.049).Conclusion Elevated CML/esRAGE ratio is associated with impaired left ventricular diastolic function, and may represent a candidate biomarker for early diastolic dysfunction. Our study also suggest that CML/esRAGE ratio may not associated with GLS abnormalities reflecting subclinical systolic dysfunction. All observations from this pilot study require further validation in large independent prospective cohorts.
SN - 1471-2261
ER -