Plasma Homocysteine as a Biomarker for Cardiovascular Risk Stratification in Children and Adolescents With Type 1...

Background Cardiovascular disease (CVD) remains the leading cause of premature morbidity and mortality among individuals living with type 1 diabetes mellitus (T1DM). Although overt cardiovascular events are uncommon during childhood, endothelial dysfunction and subclinical atherosclerosis develop early, making timely cardiovascular risk assessment essential. Plasma homocysteine has emerged as a potential biomarker of vascular injury; however, its clinical value in pediatric T1DM remains controversial, and evidence from African populations is scarce. This study aimed to evaluate plasma homocysteine concentrations in children and adolescents with T1DM and to investigate their relationship with cardiovascular risk profiles and diabetes-related complications. Methods A cross-sectional observational study was conducted at the Department of Pediatrics B, in the university hospital center of Oran, Algeria. A total of 50 children and adolescents aged 5-19 years with confirmed T1DM were included. Demographic, anthropometric, clinical, and laboratory data were retrospectively collected from medical records. Plasma total homocysteine (tHcy) concentrations, glycemic control, lipid profile, diabetes duration, insulin therapy, nephropathy, and cardiovascular risk factors were analyzed. Hyperhomocysteinemia prevalence was determined, and its association with cardiovascular risk stratification was assessed using descriptive and inferential statistical analyses. Results The study included 27 male (54%) and 23 female patients (46%), and hyperhomocysteinemia was identified in 17 of 50 participants (34%). Plasma tHcy concentrations were significantly higher in participants with HbA1c >7.5% than in those with HbA1c ≤7.5% (18.9 ± 5.8 vs. 11.8 ± 3.9 μmol/L; Student's t-test, t = 4.44, p < 0.001). Plasma tHcy concentrations were positively correlated with HbA1c (r = 0.61, p < 0.001), diabetes duration (r = 0.49, p = 0.001), LDL cholesterol (r = 0.42, p = 0.004), and triglycerides (r = 0.35, p = 0.015). Participants with diabetic nephropathy had significantly higher plasma tHcy concentrations than those without nephropathy (21.1 ± 5.9 vs. 15.2 ± 5.3 μmol/L; Student's t-test, t = 2.53, p = 0.015). In exploratory multivariable analysis, poor glycemic control (HbA1c >7.5%; aOR = 3.26, 95% CI: 1.18-9.02; p = 0.021) and diabetes duration ≥5 years (aOR = 2.54, 95% CI: 1.01-6.42; p = 0.047) were independently associated with hyperhomocysteinemia. Plasma tHcy showed good discriminative ability for the study-specific moderate-to-high cardiovascular risk classification (AUC = 0.82, 95% CI: 0.69-0.94; p < 0.001). Conclusion Hyperhomocysteinemia was prevalent among children and adolescents with T1DM in our cohort and was associated with an unfavorable cardiovascular risk-factor profile. These findings suggest that plasma homocysteine may represent a potential investigational adjunctive marker of cardiovascular risk-factor burden in pediatric T1DM. Prospective multicenter studies are warranted to validate these associations and determine their incremental clinical value beyond established cardiovascular risk factors.