**Background:** Advanced glycation end products (AGEs) are irreversible macromolecules formed by nonenzymatic reactions due to chronic hyperglycemia. They are implicated in the pathogenesis of diabetic microvascular complications. While noninvasive skin autofluorescence (sAF) has been studied in children with T1DM, the relationship between serum AGE levels and microvascular complications in this population had not been investigated. This study aimed to assess the association between serum AGE levels and microvascular complications (nephropathy, retinopathy, neuropathy) in children and adolescents with T1DM.
**Methods:** This case-control study included 84 children and adolescents (aged 9-18 years) with T1DM for more than 2 years, recruited from a pediatric endocrinology clinic between June 2021 and July 2022. Twenty-six patients had microvascular complications (nephropathy, retinopathy, peripheral neuropathy, or optic neuropathy) and 58 were complication-naive. Groups were matched for age, sex, and pubertal status. Exclusion criteria included recent ketoacidosis, severe familial hypercholesterolemia, congenital heart/kidney disease, autoimmune diseases, and eating disorders. Serum AGE levels were measured using a fluorescence method (Biovision Advanced Glycation End Products Assay Kit, Ex/Em = 360/460 nm). Microvascular complications were screened: nephropathy via urine microalbumin-creatinine ratio (uACR; microalbuminuria defined as 30-300 mg/g), retinopathy via ophthalmoscopy and fundus photography, peripheral neuropathy via neurological exam and electroneuromyography (diagnosed if vibratory perception threshold ≥20 V), and optic neuropathy via visual evoked potential (VEP) testing (abnormal if P100 wave delayed/absent). Statistical analysis used Student's t-test, Mann-Whitney U test, Kruskal-Wallis test, chi-square test, and Spearman correlation. A p-value <0.05 was considered significant.
**Key Results:** The mean age was 14.9 ± 2.5 years in the complication group and 14.1 ± 2.4 years in the no-complication group (p>0.05). Diabetes duration was significantly longer in the complication group (7.4 ± 3.6 vs. 5.6 ± 3.1 years, p=0.037). HbA1c levels were similar (8.34 ± 1.3% vs. 8.47 ± 1.1%, p=0.566). Serum AGE levels did not differ significantly between the complication and no-complication groups (49.6 ± 32.5 vs. 41.7 ± 16.4 AU/mg×10³, p=0.351). However, patients with nephropathy (n=13) had significantly higher serum AGE levels (64.8 ± 43.6 AU/mg×10³) compared to patients without complications (41.7 ± 16.4 AU/mg×10³, p=0.023). No significant differences were found for peripheral neuropathy (n=3, 39.6 ± 13.6, p=0.973), retinopathy (n=3, 28.7 ± 18.8, p=0.383), or optic neuropathy (n=14, 38.6 ± 10.6, p=0.631) when compared to the no-complication group. Serum AGE levels showed a significant positive correlation with uACR (r=0.2413, 95% CI 0.008486-0.4493, p=0.042), but not with age, diabetes duration, HbA1c, lipid profile, creatinine, or eGFR (all p>0.05). The post hoc power was 0.675 with effect size d=0.306.
**Clinical Implications:** This is the first study to evaluate serum AGE levels in relation to microvascular complications in children and adolescents with T1DM. The findings suggest that serum AGE levels are specifically associated with diabetic nephropathy, as evidenced by higher levels in nephropathy patients and a positive correlation with uACR. Serum AGEs did not correlate with retinopathy or neuropathy, possibly due to small subgroup sizes and relatively short disease duration. The study highlights the potential of serum AGEs as a biomarker for early nephropathy in pediatric T1DM, but larger, long-term studies are needed to confirm these associations and explore the role of dietary AGE intake. Limitations include the small sample size, heterogeneous complication groups, lack of healthy controls, and absence of dietary assessment.