[Association of plasma 8-hydroxy-2'-deoxyguanosine with left ventricular diastolic dysfunction in asymptomatic...

Objective: To explore the predictive value of mitochondrial oxidative stress biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHdG) and mitochondrial DNA (mtDNA) copy number in asymptomatic type 2 diabetes mellitus (T2DM) patient with left ventricular diastolic dysfunction. Methods: This was a cross-sectional study. T2DM patients without cardiovascular symptoms who were admitted to the Department of Endocrinology, the Third Affiliated Hospital of Soochow University between April 2018 and May 2022 were enrolled. According to the HFA-PEFF score, the enrolled patients were divided into three groups: the T2DM group (HFA-PEFF score ≤1), the left ventricular diastolic dysfunction suspected positive group (HFA-PEFF score 2-4), and the left ventricular diastolic dysfunction positive group (HFA-PEFF score ≥5). Multivariate logistic regression was performed to evaluate the association of plasma 8-OHdG level and mtDNA copy number with left ventricular diastolic dysfunction in patients with T2DM. Receiver operating characteristic curves were constructed to evaluate the predictive ability of plasma 8-OHdG level and its combination with baseline clinical data for left ventricular diastolic dysfunction in T2DM patients, and stratified analysis was performed by sex, age, diabetes duration and hemoglobin A1c levels. Results: A total of 163 T2DM patients without cardiovascular symptoms, aged (54.0±8.7) years, including 93 males (57.1%), were enrolled. Compared with T2DM group, patients in left ventricular diastolic dysfunction suspected positive and positive groups (44.59 (27.72, 55.58) μg/L vs. 93.23 (59.58, 129.80) μg/L vs. 101.91 (71.39, 137.39) μg/L, P<0.05) had significantly higher plasma 8-OHdG levels, while mtDNA copy number showed no statistically significant differences among the three groups (both P>0.05). Multivariate logistic regression analysis showed that after adjusting for confounder factors, elevated plasma 8-OHdG level were independently associated with both suspected positive left ventricular diastolic dysfunction (OR=1.036, 95%CI 1.019-1.053, P<0.001) and positive left ventricular diastolic dysfunction (OR=1.035, 95%CI 1.018-1.053, P<0.001). mtDNA copy number showed no significant association with T2DM accompanied by left ventricular diastolic dysfunction (P>0.05). Stratified analysis indicated that elevated plasma 8-OHdG level was significantly associated with left ventricular diastolic dysfunction in different age, sex, diabetes course and hemoglobin A1c levels subgroups (all P<0.05). The receiver operating characteristic curves indicated that the combination of baseline clinical data with 8-OhdG level (AUC=0.871, 95%CI 0.814-0.928, P<0.001) is more effective in predicting asymptomatic left ventricular diastolic dysfunction in T2DM patients than 8-OHdG (AUC=0.783, 95%CI 0.704-0.861, P<0.001) or baseline clinical data (AUC=0.736, 95%CI 0.647-0.826, P=0.001) alone. Conclusion: The mitochondrial oxidative stress biomarker 8-OHdG combined with baseline clinical data has good predictive value for asymptomatic left ventricular diastolic dysfunction in T2DM patients, and is expected to be a biomarker to identify diabetes mellitus with asymptomatic diastolic dysfunction.