Study On The Relationship Between Blood Glucose Variability And Metabolomics In Patients With Type 1 Diabetes

BackgroundThe prevalence of diabetes mellitus is increasing,but the achievement of glycemic control is not optimistic.Glycemic homeostasis is an important part of glycemic management in diabetes mellitus.Continue glucose monitoring system is an accurate method to assess glycemic variability.Glycemic variability tends to be high in patients with type 1 diabetes(T1D)and is associated with the risk of diabetes-related complications.Numerous studies have shown that changes in metabolites are associated with the risk of T1D onset and complications.Objective(1)To investigate the differences of metabolic profiles between T1D and healthy subjects.(2)To explore the differences of metabolic profiles between T1D patients with different glycemic variability.(3)To find biomarkers to distinguish T1D from healthy people and T1D patients with different glycemic variability.(4)To investigate the relationship between glycemic variability indicators and metabolomics in T1D patients.MethodIn this study,97 patients with T1D and 38 healthy controls matched for age,sex and body mass index were enrolled.Flash Glucose Monitoring system was used to obtain glucose variability indicators such as time in range(TIR).Patients were grouped according to the cut-off value of the glycemic variability index.Serum and urine samples were gathered for Untargeted metabolomics by UPLC-MS(Ultra Performance Liquid C hromatography-Mass Spectroscopy)to screen for differential metabolites and metabolic pathways.Correlation analysis was conducted with glucose variability indicators and differential metabolites.Results(1)The major differential metabolites between T1D and healthy population were taurocholic acid,tyrosyl-proline,valinyl-valine and acetylcysteine in serum and cotinine glucuronide,tetrahydroaldosterone-3-glucuronide and gamma-glutamylphenylalanine in urine,all of which could be used as biomakers for differentiation between T1D and healthy subjects(combined AUCblood=0.871,combined AUCurine=0.954).(2)Serum aspartyl-arginine,nicotinic glucuronide and alanyl-proline and urine piperoninine and thromboxane B3 were the main differential metabolites for TIR>70%or TIR?70%in T1D patients.The combination as biomarkers in different samples had good role in identifying high and low TIR groups(combined AUCblood=0.808,combined AUCurine=0.885).The differential metabolic pathways among patients with T1D with different glycemic variability mainly included tryptophan metabolism,urea cycle/amino group metabolism,biopterin metabolism,purine metabolism,and bile acid synthesis.(3)Acetylcysteine and taurocholic acid were significantly and positively correlated with CV,TAR,SD,MODD,MAGE,and HBGI.Tyrosyl-proline,valinyl-valine,and tetrahydroaldosterone-3-glucuronide were significantly and positively correlated with TIR.Valinyl-valine was an independent predictor of TIR after correction for confounding factors.ConclusionsThere exist differences in metabolic profiles between T1D and healthy populations and between T1D patients with different glycemic variability.Oxidative stress may be involved in the mechanism of glycemic variability in T1D patients.By combining differential metabolites with clinical indicators,it may be possible to better stratify glycemic variability in T1D patients and thus guide the refined management of glycemia in diabetic patients.