CML / esRAGE ratio is associated with impaired diastolic function in type 1 diabetic patients with normal ejection fraction and without known heart disease

Introduction: Heart failure is a common complication of diabetic microangiopathy, so early identification of myocardial dysfunction is crucial. Advanced glycation end products (AGEs) play an important role in diabetic cardiomyopathy. Soluble receptor for AGEs (sRAGE) and endogenous secretory receptor for AGEs (esRAGE) are novel cardiovascular biomarkers. This study aimed to explore whether soluble RAGE is associated with early cardiac dysfunction evaluated by advanced echocardiography. Methods: We enrolled 29 type 1 diabetic patients without known heart disease and with normal left ventricular ejection fraction (LVEF ≥ 50%) and 31 healthy controls. Traditional, tissue Doppler, and speckle tracking echocardiography were performed. Plasma levels of carboxymethyl lysine (CML), methyllysine hydroimidazolone (MG-H1), sRAGE, and esRAGE were detected. A multivariable model with significant covariates was used to study the relationship between myocardial function and these indexes. Results: In the case group, regional systolic longitudinal strain (LS) in most left ventricle segments (13/18), global systolic longitudinal strain (GLS), and peak velocity at the lateral corner of the mitral annuls during early diastole (e(lat)) were significantly lower than those in the control group, while E/e (lat) was higher. CML levels and CML/esRAGE ratio increased, and esRAGE decreased in the case group. Conclusion: Elevated CML/esRAGE indicates impaired left ventricular diastolic function, serving as a marker for it. However, it is insensitive to GLS abnormalities, which often suggest subclinical systolic dysfunction.