| ObjectiveTo explore the relationship between type 1 diabetes mellitus(T1DM)and cognitive function by cognitive tests,and to detect metabolic changes in the hippocampus and brain functional connectivity changes used proton magnetic resonance spectrum(1H-MRS)and resting-state functional magnetic resonance imaging(fMRI).We also analysis the level of soluble high-mobility group box-1(HMGB1)by enzyme-linked immunosorbent assay(ELISA)and HbA1 C,blood glucose fluctuation in the type 1 diabetes patients in order to find the brain strcture changes,the risk factors and biological indicators of the cognitive impairment.Methods1.The 66 participants were recruited at the People's Hospital of Zhengzhou University,they were divided two groups: T1 DM group,normal control group.2.Recorded general information of participants such as age,height and other datas.The levels of HMGB1,interleukin-1?(IL-1?),interleukin-6(IL-6)and tumornecrosis factor-?(TNF-?)in serum were measured by ELISA.The continuous glucose monitoring system(CGMS)device was used to obtain 72 h glycemic data.2.A battery of cognitive tests were chosen to measure cognitive function: Digit Symbol Substitution Test(DSST),Digit span test(DST),Trail Making Test A / B(TMT-A/TMT-B),Rey Auditory Verbal Learning Tests(RAVLT),Rey-Osterrieth Complex Figure(ROCF).3.The NAA,Cho,Cr of hippocampus were determined by1H-MRS.All participants underwent 3.0 Tesla fMRI examination in resting state,the functional connection between other brain regions and left hippocampus(seed region)was analyzed by Granger analysis.4.All statistical analyses were performed using SPSS19.0 software package.Results1.Comparison in two groups by the clinical information and lipid and inflammatory cytokinesNo significant differences were find between two groups in age,sex,smoking,education level,BMI(P > 0.05),the T1 DM group had a significantly lower mean score of LDL-C than normal control group(P<0.05),The T1 DM had higher level of HMGB1,IL-1?,TNF-? and IL-6 than those in normal control group(P <0.05).2.Diabetes duration and HbA1 C and Glucemic fluctuation of T1 DM patientsThe average T1 DM duration was 9.2±6.0 years,HbA1 C of the T1 DM group was 9.44±2.41%,glucose fluctuation parameters of the T1 DM group: the mean blood glucose(MBG)was 9.43±2.44mmol/l,the glucose excursions(MAGE)was6.20±2.24mmol/l,the mean of daily differences(MODD)was 3.87±1.58mmol/l,the standard deviation of blood glucose(SDBG)was 2.39±0.85mmol/l,low blood glucose index(LBGI)was 2.50±2.44,the lower than 3.9 mmol / l(glu70)was3.37±3.88%.3.The differences in two groups in cognition and hippocampal metabolism,brain functional connections.The T1 DM group had lower mean score of DSST,sum of RAVLT trials(1-5)and ROCF copy than normal control group(P<0.05).There were no significant group differences on TMT,RAVLT delayed recall,DST and ROCF delayed recall(P > 0.05).Decreased NAA/Cr was observed in the T1 DM group relative to normal control group in left hippocampus(P<0.05).No significant differences were detested between two groups in NAA/Cr in the right hippocampus and bilateral Cho/Cr(P >0.05).The T1 DM group showed increased functional connectivity of the right angular gyrus,the bilateral suferior parietal gysus,partial Wernicke's area with left hippocampus(P<0.05).The T1 DM group showed decreased functional connectivity of the bilateral subcuneiform nucleus,the bilateral superior frontal lobe and the bilateral middle frontal lobe,the left superior occipital lobe,supplementary motor area,the bilateral precentral gyrus,the bilateral postcentral gyrus with left hippocampus(P<0.05).4.Correlation analysis of T1 DM groupThe level of education,HbA1 C,MAGE,SDBG,HMGB1,TNF-?,the level of Cho/Cr in right hippocampus were correlated with DSST(P<0.05).MODD?SDBG were related to DST(P < 0.05).The level of education,MAGE,HMGB1,TNF-?were related to TMT-B(P<0.05).The level of education,MAGE,SDBG,HMGB1,IL-1?,IL-6,the level of NAA/Cr in left hippocampus were correlated with sum of RAVLT trials(1-5)(P<0.05).HMGB1,IL-1?,IL-6 were related to RAVLT delayed recall(P<0.05).Age,LBGI were related to ROCF copy(P<0.05).MAGE was related to HMGB1(P<0.05),there was not association between HbA1 C and HMGB1(P<0.05).HMGB1 were related to IL-1??TNF-??IL-6(P<0.05).MODD,glu70,were related to the level of NAA/Cr in left hippocampus(P<0.05),GLU70 was related to the level of Cho/Cr in left hippocampus(P < 0.05),HMGB1 was not related with hippocampal metabolism(P<0.05).Multivariate linear regression analysis:the level of education and HbA1 C,SDBG,HMGB1 were risk factors of DSST.MODD and HbA1 C were risk factors of DST.The level of education and HMGB1 were risk factors of TMT-B.MAGE and SDBG,the level of NAA/Cr in left hippocampus were risk factors of sum of RAVLT trials(1-5).MODD and HMGB1 were risk factors of RAVLT delayedrecall.Age,HMGB1 and the level of NAA/Cr in left hippocampus were risk factors of ROCF copy.Conclusion1.The T1 DM patients have lower cognitive function in three domains:information processing speed,memory and visuospatial.2.The T1 DM patients have lower compared with the normal person in the level of NAA in the left hippocampus decrease.The T1 DM patients show the function connection changes of the left hippocampus and some brain areas.The reduction of NAA in left hippocampus is the factors of short term memory.These may be the structural basis of cognitive decline in T1 DM patients.3.HbA1 C and glucose fluctuation are the factors of type 1 diabetes mellitus with cognitive decline.Glucose fluctuation relate to cognition decline which the HMGB1-mediated inflammatory pathways was involved in these effects. |
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