Serum Homocysteine, Insulin Resistance, and Metabolic Risk Factors in Children and Adolescents with Obesity: A Retrospective Cross-Sectional Study

<b>Objective:</b> The aim of this study was to evaluate serum homocysteine levels in obese children and adolescents and to examine their relationships with insulin resistance, metabolic risk factors, and vitamin B12, folate, and vitamin D status. <b>Methods:</b> A single-center, retrospective cross-sectional observational study included 102 children and adolescents with obesity attending a tertiary pediatric obesity clinic. Clinical, anthropometric, and biochemical data were analyzed. Group comparisons were performed according to obesity severity and presence of hyperhomocysteinemia. Correlation analyses and multivariable linear regression were conducted to identify independent predictors of serum homocysteine levels. <b>Results:</b> The median serum homocysteine level was 9.5 (7.82-11.8) µmol/L, and hyperhomocysteinemia was present in 27.5% of cases. Insulin resistance was significantly more prevalent in children with severe obesity compared to those with obesity (90.6% vs. 64.3%; OR 5.29, 95% CI 1.41-29.8; <i>p</i> = 0.008). Serum homocysteine levels were positively correlated with age, BMI, fasting glucose, insulin, and HOMA-IR, and negatively correlated with vitamin B12 and folate levels (all <i>p</i> < 0.05). Folate deficiency was significantly more common in participants with hyperhomocysteinemia (33.3% vs. 6.7%; OR 6.82, 95% CI 1.80-29.37; <i>p</i> = 0.002). In multivariable regression analysis, age (β = 0.433; <i>p</i> = 0.001) and folate levels (β = -0.235; <i>p</i> = 0.032) were independently associated with serum homocysteine concentrations. <b>Conclusions:</b> Hyperhomocysteinemia is present in approximately one-quarter of children with obesity and may represent a relevant metabolic alteration in this population. Although serum homocysteine levels were correlated with insulin resistance in univariable analyses, multivariable regression analysis identified age and folate levels as independent determinants. These findings highlight the potential clinical importance of evaluating folate status in children with obesity, particularly in those with elevated homocysteine levels. Prospective studies are warranted to determine whether folate supplementation can effectively reduce homocysteine levels and improve long-term cardiometabolic risk in pediatric obesity.