A Cross-sectional Study On The Evaluation Of Blood Glucose Variability In Chinese Adults With Type 1 Diabetes By Scanning Glucose Monitoring System And The Relationship Between Intestinal Flora And Blood Glucose Variability

Part one Evaluation of glucose variability of Chinese adult type 1 diabetes by flash glucose monitoring system—a cross-sectional studyObjectiveIn China,adult type 1 diabetes(T1D)is the main population of T1D patients whose blood glucose is difficult to manage,but little is known about their glucose variability.In this study,we evaluated the value of glucose metrics derived from the flash glucose monitoring system(FGM)in the management of Chinese adult T1D.We also evaluated the glucose variability of T1D and analyzed the possible related factors.MethodsAdult T1D patients were admitted from the outpatient department of Peking Union Medical College Hospital(PUMCH).Detailed medical history was recorded,while physical examination,biochemical tests,and mixed-meal tolerance test(MMTT)were carried out.All patients wore FGM to have their glucose variability assessed.Statistical analysis was carried out using SPSS 25.The relationship between FGM-derived glucose variability indicators and their relationship with glycated hemoglobin(HbAlc)was also investigated.We analyzed the relationship between glucose variability and diet pattern,islet function and insulin sensitivity.ResultsThis study included 94 adult T1D patients,with a median age of 35(19)years and a median disease duration of 7.7(10.4)years.In this study,only 38.3%of the patients achieved an HbA1c less than 7%and 19.1%had a time in range(TIR)higher than 70%.Only 35.1%of patients met the target of the time below range(TBR).36.2%of the patients were with a glucose variation coefficient(CV)that was less than 36%.Patients without chronic complications had lower standard deviation(SD),lower low blood glucose index(LBGI),and lower M value.Patients with preserved islet function tended to achieve lower glucose variability,while diet pattern and insulin sensitivity seemed to have no effect on glucose variability.There was a linear negative correlation between FGM-derived TIR and HbAlc,which was similar to that between TIR derived from other continue glucose monitoring systems(CGM)and HbAlc.However,the relationship between the two indicators is affected by the CV level.ConclusionsAdult T1D patients in this study were with poor glycemic control:low rate of HbA1c within a target range,high glucose variability and high risk of hypoglycemia.FGM-derived TIR can be used in the blood glucose management of adult T1D in China.However,the relationship between TIR and HbAlc is affected by CV.Prospective studies with high quality are needed to further clarify the relationship between TIR and chronic diabetes complications,to set up a more reasonable target of TIR for T1D patients.Part two A preliminary study on the relationship between intestinalmicrobiota and glucose variability in Chinese adult type 1 diabetesObjective Numerous studies have shown changes in the intestinal microbiota in children with type 1 diabetes(type ldiabetes,T1D),but studies in adults with T1D are scarce.Theintestinal microbiota is involved in regulating glucose metabolism.Previous studies haverevealed that intestinal microbiota affects postprandial glycemic responses(PPGR)in normal people.Some bacteria may be correlated with HbA1c levels of T1D.This study aims to reveal the structure and composition of the intestinal microbiota of Chinese adult T1D,and to explore the relationship between intestinal microbiota and blood glucose variability,to provide new thoughts in potential therapeutic targets for improving T1D blood glucose variability.Methods This study included 29 adult T1D patients(T1D group)and 20 healthy controls(CONgroup)in the Beijing area.T1D group and CON group are matched by gender,age,andbody mass index(BMI).16s rDNA V3-V4 region sequencing on the intestinal microbiota of T1D and healthy subjects was performed by Illumina Miseq sequencing platform.We compared the intestinal microbiota of adult T1D patients with healthy subjects.Flash glucose monitoring system(FGM)was used to assess the blood glucose variability of T1D patients,and the relationship between intestinal microbiota and blood glucose variability was explored in T1D patients.Results The average age of T1D patients was 32.2±6.4 years with a median disease durationof 7.7(2.8,13.6)years.The average glycated hemoglobin(HbA1c)was 7.4 ± 1.4%,whilethe time in range(TIR)was 48.35%(23.7%,58.9%).Time above range(TAR)was 11.65%(2.2%,23.5%)and time below range(TBR)was 4.6%(2.3%,8.9%).The standard deviation of glucose(SD)was 3.3±1.0mmol/L and coefficient of variation(CV)was 40.2± 7.9%,with a mean amplitude of glycemic excursions(MAGE)of 7.8 ± 2.5mmol/L and a mean daily differences(MODD)of 3.3±1.2mmol/L.A total of 689 different OTUs were confirmed in the OTU cluster analysis,while 630 OTUs in the T1D group and 575 OTUs in the CON group.One hundred and fourteen OTUs were unique to the T1D group,and 59 OTUs were unique to healthy controls.There were 28 different OTUs between T1D and healthy controls,but the FDR-P>0.05.There was no significant decrease in αdiversity in patients with T1D.β diversity showed that there was a difference between the structure of the intestinal microbiota of T1D and healthy controls,however,no statistical significance was achieved.Lefse analysis showed that the relative abundance of Verrucomicrobia,Verrucomicrobiae,Verrucomicrobiales,Verrucomicrobiaceae,Lachnospiraceae,Akkermansia,and Lachnospiracea_incertae sedis in T1D was higher than healthy controls,while no statistical significance was achieved in the wilcox.test.HbA1c was negatively correlated with Faecalibacterium and Blautia,while Lachnospiracea_incertae_sedis was negatively correlated with SD,MAGE,and MODD.TIR was higher in the patients with positive Intestinimonas,while CV,HbA1c,and TAR were lower.In the patients with positive Fusobacterium,TIR was lower,while HbA1c,TAR,high blood glucose index(HBGI),SD,MAGE,and MODD were higher.Whether Intestinimonas or Fusobacterium exist were both independent predictors of TIR.Conclusions The diversity and structure of intestinal microbiota in non-newly-diagnosed Chinese adult T1D patients with mean HbA1c less than 8%were similar to healthy controls.Intestinal microbiota,especially butyrate-producing bacteria in the gut,was correlated with blood glucose variability and may be a potential therapeutic target for improving T1D glucose variability,and further study is needed to confirm our results and deeply investigate the possible mechanism.