α-Dicarbonyls and advanced glycation end products (AGEs) may contribute to the pathogenesis
of insulin resistance by a variety of mechanisms. To investigate whether young insulin-resistant
subjects present markers of increased dicarbonyl stress, we determined serum α-dicarbonyls-methylglyoxal,
glyoxal, 3-deoxyglucosone; their derived free- and protein-bound, and urinary AGEs
using the UPLC/MS-MS method; soluble receptors for AGEs (sRAGE), and cardiometabolic
risk markers in 142 (49% females) insulin resistant (Quantitative Insulin Sensitivity
Check Index (QUICKI) ≤ 0.319) and 167 (47% females) age-, and waist-to-height ratio-matched
insulin-sensitive controls aged 16-to-22 years. The between-group comparison was performed
using the two-factor (sex, presence/absence of insulin resistance) analysis of variance;
multiple regression via the orthogonal projection to latent structures model. In comparison
with their insulin-sensitive peers, young healthy insulin-resistant individuals without
diabetes manifest alterations throughout the α-dicarbonyls-AGEs-sRAGE axis, dominated
by higher 3-deoxyglucosone levels. Variables of α-dicarbonyls-AGEs-sRAGE axis were
associated with insulin sensitivity independently from cardiometabolic risk markers,
and sex-specifically. Cleaved RAGE associates with QUICKI only in males; while multiple
α-dicarbonyls and AGEs independently associate with QUICKI particularly in females,
who displayed a more advantageous cardiometabolic profile compared with males. Further
studies are needed to elucidate whether interventions alleviating dicarbonyl stress
ameliorate insulin resistance.
