We examined the relationships of tryptophan (Trp) and the metabolites of the kynurenine pathway (KP) to the occurrence of type 2 diabetes (T2D) and metabolic risk factors in obese middle-aged women. The study included 128 obese women divided into two subgroups: a normoglycemic group (NG, n = 65) and a T2D group (n = 63). The concentrations of serum tryptophan (Trp), kynurenine (Kyn), 3-hydroxykynurenine (3HKyn), quinolinic acid (QA), and kynurenic acid (Kyna) were analyzed using ultra-high-performance liquid chromatography coupled with electrospray ionization/triple quadrupole mass spectrometry. Blood biochemical parameters and anthropometric parameters were measured. The women with T2D had significantly higher Trp, Kyna, Kyna/QA ratio, and Kyna/3HKyn ratio values than the NG women. Logistic regression analysis showed that the concentrations of Trp and Kyna and the values of the Kyna/3HKyn ratio were most strongly associated with T2D occurrence, even after controlling for confounding factors. The model with Trp level and Kyna/3HKyn ratio accounted for 20% of the variation in the presence of T2D. We also showed a different pattern of correlations between kynurenines and metabolic factors in the NG and T2D women, which was mostly reflected in the stronger relationship between BMI and KP metabolites in the NG obese women. An increase in Trp and Kyna levels with an accompanying increase in Kyna/3HKyn ratio value is associated with the occurrence of T2D in obese middle-aged women.

We examined the glycemic status-stratified relationships between total serum branched-chain amino acid (BCAA) concentrations and cardiometabolic risk factors in middle-aged Caucasian women. The study included 349 women divided into 2 subgroups: a normoglycemic group (NG, n = 184) and a dysglycemic group (DG, n = 165). Blood samples, anthropometric parameters, and blood pressure were measured. HOMA-IR, albumin-corrected calcium (CCa), and fatty liver index (FLI) were calculated. BCAA concentrations were higher in the women with dysglycemia. BCAAs moderately correlated with BMI and FLI in the NG group and with BMI, FLI, total calcium (TCa), CCa, HbA1c, TG/HDL-C, and HDL-C in the DG group. After adjusting for age and BMI, correlations for TCa, CCa, HbA1c, HDL-C, and TG/HDL-C remained significant. The coexistence of increased BCAAs with dysglycemic status was associated with markedly higher concentrations of TCa, CCa, HbA1c, and TG, which were not observed in the DG women with low level of BCAAs. Multiple regression showed that TCa or CCa, age and BCAAs were significantly associated with HbA1c independently of BMI only in the DG group. We conclude that dysglycemia in particular predisposes women to a significant relationship between total BCAAs and circulating calcium and HbA1c, and that these relationships are independent of BMI and may reflect the pathophysiological calcium-dependent mechanisms connecting BCAAs with metabolic disturbances.