Three phosphatidylcholines as a potential early-diagnostic signature for hyperglycemia in preschool-aged children: a cross-sectional pilot study.

OBJECTIVE

Although lipid metabolism dysregulation commonly accompanies elevated blood glucose, lipidomic studies in hyperglycemic children remain limited. We hypothesized that distinct lipid metabolic signatures and derived lipid ratios are associated with pediatric hyperglycemia and may aid in its identification.

METHODS

Based on the Infant Development and Health Cohort, 59 preschool-aged children (3-4 years) with fasting plasma glucose (FPG) ≥ 5.6 mmol/L were randomly selected from 210 participants, alongside 60 matched healthy controls (FPG < 5.6 mmol/L). Semiquantitative lipidomics was performed, and lipid ratios were calculated from identified characteristic lipids. Univariate and multiple regression analyses were conducted.

RESULTS

After adjusting for age, sex, body mass index (BMI), early-life risk factors, and metabolic disorder factors, six lipid species remained independently associated with FPG variations (Bonferroni-adjusted p < 0.05). Lipid ratios derived from these six lipids differed significantly between groups; the decreased levels of phosphatidylethanolamine/diacyl-phosphatidylcholine was significantly correlated with elevated FPG, whereas elevated levels of ether-phosphoatidylcholine/diacyl-phosphoatidylcholine ratios was significantly associated with elevated FPG. Three phosphatidylcholine species showed good diagnostic performance (AUC = 0.811, 95% CI: 0.733-0.881). Their composite signature outperformed both the baseline model (age, sex; AUC: 0.882 vs. 0.584, DeLong's p < 0.001), and the extended risk factor model (age, sex, BMI, and early-life riskr factors, AUC: 0.882 vs. 0.635, DeLong's p < 0.001). The robustness of the three PCs was further supported by sensitivity analyses, which demonstrated consistent performance using Firth penalized regression (AUC = 0.883) and an alternative FPG cutoff at the 75th percentile (AUC = 0.834).

CONCLUSIONS

In this cross-sectional targeted lipidomics study, a three PC lipid panel was independently associated with subclinical hyperglycemia in preschool-aged children and showed robust diagnostic performance. Two lipid ratios were also associated with FPG. These findings identify a potential lipid panel for early risk detection in this understudied population, pending validation in larger cohorts.