Relationship Between Abnormal Kynurenine Metabolism And Glucose Insulin Level In First-episode Schizophrenia

Objective Patients with first-episode schizophrenia are at significantly increased risk of impaired glucose and insulin metabolism,However,the pathophysiological mechanism has not been elucidated.Previous studies suggested that abnormalities in the kynurenine pathway might be the pathogenesis of the risk of hyperinsulinemic glucose metabolism.They supposed that abnormal of kynurenines leads to the decrease of the level of plasma insulin,that leads to the increase of blood glucose and eventually the occurrence of diabetes.In this study a case-control study was conducted to investigate the relationship between the abnormality of kynurenines and the risk of glucose insulin metabolism in first-episode schizophrenia.Methods A cross-sectional study was conducted in this study,a total of 160 first episode patients with schizophrenia(FEPS)and 122 age-,gender-,education-matched healthy controls(HC)were recruited.Serum levels of tryptophan,Kynurenine,kynurenic acid and quinolinic acid were measured using liquid chromatography-tandem mass spectrometry;The relationships between glucose-insulin metabolism measures and the kynurenines were investigated by the bivariate correlation and multiple regression.Results The FEPS had higher levels of fasting plasma glucose[median(quartile 1,quartile 3):5.45(4.80,6.38)mmol/Lvs.5.10(4.80,5.40)mmol/L,Z=-3.93,p<0.001]and lower levels of fasting plasma insulin[6.22±2.88pmol/L vs.7.23±4.04pmol/L,t=-2.45,p=0.015]than the HC.The levels of tryptophan[median(quartile 1,quartile 3):11449.53(10053.51,12828.46)nM vs.16780.00(13735.00,18997.50)nM,Z=-10.69,p<0.001],kynurenine[median(quartile 1,quartile 3):252.17(208.75,307.43)nM vs.637.80(355.45,827.35)nM,Z=-11.02,p<0.001],kynurenic acid[median(quartile 1,quartile 3):4.96(3.67,6.90)nM vs.11.00(8.47,14.25)nM,Z=-11.48,p<0.001]and quinolinic acid[median(quartile 1,quartile 3):39.72(30.98,47.34)nM vs.53.16(44.65,68.55)nM,Z=-8.29,p<0.001]in the FEPS were significantly lower than those in the HC.Furthermore,our results showed the kynurenic acid levels was positive correlated with the insulin levels(r=0.46,p<0.001)the FEPS.Conclusions Fasting plasma glucose concentration increased and fasting plasma insulin level decreased in patients with first-episode schizophrenia.The level of kynurenines in patients with schizophrenia is decreased,which is associated with the risk of hyperinsulinemic glucose metabolism.The decrease of plasma kynurenic acid was positively correlated with the decrease of fasting plasma insulin level,so plasma kynurenic acid maybe a potential common mechanism of schizophrenia and abnormal glucose-insulin metabolism.