Global deoxyribonucleic acid methylation and telomere length in patients with systemic metabolic disorders

Abstract

ABSTRACT Background: Epigenetic mechanisms reflect biological ageing and cardiometabolic risk. In patients with systemic metabolic disorders (SMD), these processes are perturbed, yet joint dynamics of global 5-methylcytosine (5-mC) and telomere length remain insufficiently described. Aims: To assess associations between 5-mC, telomere length and cardiometabolic profiles by SMD stage and over time. Methods: We studied 78 SMD patients (median age 55.4 years; 56% men): stage 1 (n=59) and stage 2 (n=19). Global 5-mC was measured by enzyme-linked immunosorbent assay and telomere length by real-time quantitative polymerase chain reaction. 67 patients had a follow-up visit after a median of 63 weeks. Results: Stage 2 patients showed higher body mass index, aspartate/alanine aminotransferases, alkaline phosphatase, glucose, triglycerides, very-low-density lipoprotein cholesterol, and lower high-density lipoprotein cholesterol (all p<0.05). Only trends toward hypermethylation and shorter telomere length were observed in stage 2. Within stage 1, 5-mC associated with hematocrit; telomere length associated with red blood cell count, platelet distribution width, and total cholesterol. Within stage 2, alkaline phosphatase inversely predicted 5-mC; telomere length was predicted by age, body weight, erythrocyte sedimentation rate, mean corpuscular hemoglobin concentration, alkaline phosphatase, creatinine, and uric acid (all p<0.05). Change in 5-mC related to baseline body mass index, mean corpuscular volume, glucose, red cell distribution width, mean platelet volume, creatinine, and low-density lipoprotein cholesterol; telomere length change related to baseline glucose, direct bilirubin, and albumin (all p<0.05). Conclusions: Stage 2 SMD reflects greater metabolic burden with unfavorable 5-mC, telomere length trends. Cardiometabolic indices show independent links with 5-mC, telomere length, supporting composite biomarker strategies for ageing-risk monitoring in SMD.