ApoB48 (remnant) Dyslipoproteinemia Correlates with D-lactate, an Advanced Glycation Precursor Catabolic Product, in Obese Adolescents

Abstract

BackgroundMethyglyoxal (MG) is a toxic molecule that mediates damage produced by glycation, a key pathogenic factor in diabetes mellitus. We have previously shown that the MG catabolic product, D-lactate, is higher in obese adolescents (1) and that apoB48 is higher in adolescents with insulin resistance (IR) (2). Hypothesis and aims: We tested the hypothesis that increased D-lactate is associated with ApoB48 (remnant) dyslipoproteinemia and IR in adolescents. Material and MethodsThis cross-sectional study in anew cohort included euglycemic adolescents between 15 and 19 years old, classified in 4 groups according to BMI and HOMA-IR: lean adolescents without (MHL) alterations (n = 20), lean adolescents with metabolic alterations (MUL, n=20) metabolically healthy obese (MHO) n = 20 and metabolically unhealthy obese adolescents (MUO) n = 24. ResultsD-lactate levels did not differ between MHL and MUL participants (0.29 +/- 0.15 vs 0.29 +/- 0.13 mmol/L), they show a trend to be higher in MHO (0.38 +/- 0.15 mmol/L) and are significantly higher (0.46 +/- 0.15 mmol/L) in MUO vs MUL or MHL (p=0.003. D-lactate correlated with BMI (Rho=0.39, p=0.0002); HOMA-IR (Rho=0.33, p=0.002) and apoB48 HOMA-IR (Rho=0.33, p=0.002). Conclusion: MUO displayed 58% higher levels of D-lactate than lean adolescents. D-lactate correlates with BMI, HOMA-IR and with chylomicron remnants. We suggest that IR does not suffice to produce increased MG metabolism (MHL and MUL have the same levels) but potentiates the effect of obesity. Increased D-lactate show dysregulation of glycolysis leading to MG production, in association with poor chylomicron catabolism. 1. Rodríguez-Mortera, Reyna, Claudia Luevano-Contreras, Sergio Solorio-Meza, Russell Caccavello, Yasmin Bains, Ma Eugenia Garay-Sevilla, and Alejandro Gugliucci. Clinical Chemistry and Laboratory Medicine (CCLM) 56, no. 7 (2018): 1100-1108. 2. Rodríguez-Mortera R, Caccavello R, Garay-Sevilla ME, Gugliucci A. Clin Chim Acta. 2020; 508:61-68. doi:10.1016/j.cca.2020.05.014