| Objective: Though with a rather lower incidence of 1/100000 in China,Type 1diabetes mellitus(T1 DM)has a higher risk of disability and death than Type 2 diabetes.Heart failure is the most common cause of death in T1 DM patients.Coronary artery microcirculation injury,myocardial interstitial fibrosis and cardiac systolic and diastolic dysfunction caused by hyperglycemia are the main inducements leading to heart failure.Early identification of subclinical myocardial injury in asymptomatic pediatric and young T1 DM patients is helpful for risk stratification and guidance of clinical treatment.Therefore,the purpose of this study is to :(1)evaluate the coronary microcirculation injury in children and young adults with T1 DM by using the firstpass perfusion technique of cardiovascular magnetic resonance(CMR),and to explore the correlation between clinical indicators,left ventricular function indexes and coronary microcirculation in children and young adults with T1 DM for further;(2)CMR cine images and Native T1 value and extracellular volume(ECV)acquired through T1 mapping technology were used to quantitatively evaluate cardiac function and myocardial tissue characteristic in pediatric and adult T1 DM patients,and to explore the correlation between clinical indexes,cardiac function and cardiac tissue characteristic parameters furtherly;(3)Cardiac function,coronary microcirculation and myocardial deformation in asymptomatic subclinical pediatric and adult T1 DM patients without symptoms were evaluated by CMR cine and first-pass perfusion technique,the correlation among cardiac function,perfusion parameters and myocardial deformation was explored,and to explore the value of left ventricular strain parameters in the evaluation of subclinical myocardial injury in T1 DM patients.Materials and Methods: 51 patients with T1DM(33 patients in T1 DM children group and 18 patients in T1 DM adults group)and 34 age-and sex-matched healthy controls(21 healthy subjects matched children group,13 healthy subjects matched adults group)were included in the first chapter of this study.All subjects underwent 3.0T CMR cardiac cine imaging and first-pass perfusion scan.Clinical characters of these T1 DM patients including BMI,waist circumference,hip circumference,Hb A1 c,urinary protein,urinary creatinine,and urinary protein/creatinine were recorded.The parameters acquired from first-pass perfusion techniques in T1 DM patients were analyzed,including the maximal upslope of myocardial intensity enhancement(Slopemax),time to peak(tpeak),and peak signal intensity(SIpeak)of the basal,mid,and apical segment of left ventricle.All these parameters were compared between subgroups and matched healthy controls.Spearman rank correlation and multiple linear regression were used to analyze the correlation between the parameters of first-pass perfusion in left ventricle and the clinical characters and cardiac function parameters.50 T1 DM patients(32 patients in T1 DM children group and 18 patients in T1 DM adult group)and 40 age-and sex-matched healthy controls(23 healthy subjects matched children group,17 healthy subjects matched adults group)were included in Chapter 2 of this study.All subjects underwent 3.0T CMR cardiac cine imaging and native/post T1 mapping sequence imaging.Clinical characters of these T1 DM patients including BMI,waist circumference,hip circumference,Hb A1 c,urinary protein,urinary creatinine,and urinary protein/creatinine were recorded.Native T1,post-T1 and ECV values of global,basal,mid,and apical segment in left ventricle were acquired and compared between subgroups and matched healthy controls.Spearman rank correlation analysis was used to investigate the correlation among T1 mapping parameters and clinical characters,cardiac function and myocardial perfusion parameters.In 3rd part of this study,a total of 51 patients with T1DM(34 patients in T1 DM children group and 17 patients in T2 DM youth group)and 39 age-and sex-matched healthy controls(23 healthy subjects matched children group,17 healthy subjects matched adults group)were included.All subjects underwent 3.0T CMR cardiac cine imaging,including four-chamber long axis,two-chamber long axis and short axis,and first-pass perfusion.Myocardial deformation indexes,including global peak strain radial(GPSR),global peak strain circumferential(GPSC),global peak strain long(GPSL),basal peak stain radial(BPSR),basal peak strain circumferential(BPSC),basal peak strain long(BPSL),mid peak strain radial(MPSR),mid peak strain circumferential(MPSC),mid peak strain long(MPSL),apical peak strain radial strain(APSR),apical peak strain circumferential strain(APSC),apical peak strain long(APSL).Spearman rank correlation and multiple linear regression were used to investigate the correlation among those myocardial strain indexes,cardiac function and myocardial perfusion parameters.Receiver operating characteristic(ROC)curve was performed to explore the value of myocardial strain indexes for distinguish the asymptomatic subclinical T1 DM patients with left ventricular systolic dysfunction.Results: In first chapter of this study,we found that perfusion parameters of basal and apical segments of left ventricle in T1 DM patients were significantly reduced compared with healthy control group,(Slopemax in the basal segment: 3.05±1.67 vs.3.73±1.32,P=0.021;SIpeak in basal segment: 29.55±6.94 vs.34.36±8.74,P=0.009;Slopemax in apical segment: 4.04±2.10 vs.4.90±1.99,P=0.047).In the subgroup comparison,there was no significant difference in all the fist-pass perfusion parameters of left ventricle between children T1 DM group and child healthy control group(all P>0.05).Significant myocardial microcirculation dysfunction was found in the basal,middle and apical segments of the left ventricle in the young T1 DM group(Slopemax in the basal segment: 2.56±1.32 vs.4.10±1.56,P=0.012;SIpeak in basement: 27.01±7.03 vs.34.72±9.58,P=0.004;Slopemax: 3.23±1.55 vs.4.72±1.96,P=0.025;SIpeak: 32.55±8.72 vs.39.29±11.15,P=0.025;Slopemax of apical segment: 3.65±1.72 vs.5.08±2.34,P=0.046).Multivariable linear regression analysis showed that urinary protein/creatinine was positively correlated with basal SIpeak,apical Slopemax and mid SIpeak(all P < 0.05).In addition,there was a negative linear correlation among left ventricular remodeling index and mid Slopemax and apical SIpeak(all P<0.05).In second chapter of this study,all enrolled subjects were negative for LGE.Compared with the healthy control group,global and segmental ECV of the left ventricle in T1 DM patients was significant increased(global ECV: 25.02±2.76% vs.23.13±1.98%,P=0.001;basal ECV: 24.47±2.69% vs.22.58±2.44%,P=0.001;mid ECV: 24.69±2.83% vs.23.23±1.95%,P=0.008;apical ECV: 25.56±2.81% vs.24.00±255%,P=0.006).In subgroup comparison,both the post-T1 value and ECV value in children T1 DM group increased significantly(global postT1:526.84±93.53 ms vs.467.35±53.74 ms,P=0.027;basal Post-T1: 510.23±96.74 ms vs.447.26±59.36 ms,P=0.024;mid Post-T1: 523.19±88.27 ms vs.469.26±54.58 ms,P=0.041;global ECV: 25.50±2.63% vs.23.52±2.33%,P=0.006;basal ECV: 24.77±2.50% vs.22.91±2.87%,P=0.014;mid ECV: 25.26±2.67% vs.23.65±2.17%,P=0.022).What’s more,ECV value of left ventricle in the young T1 DM group was higher than that of the healthy adult control group(global ECV: 24.17±2.85% vs.22.59±1.23%,P=0.043;basal ECV: 23.94±3.00% vs.22.12±1.65%,P=0.033).Negative correlations were identified among global ECV,waist circumference and hip circumference;among global post-T1,BMI and hip circumference;between global native T1 and hemoglobin A1c(all P<0.05).Meanwhile,left ventricular enddiastolic volume,left ventricular end-systolic volume,stroke output,blood output,myocardial mass,and left ventricular remodeling index were negatively correlated with global ECV(all P<0.05).There was no correlation between left ventricular perfusion parameters and T1 mapping parameters(all P > 0.05).In the third chapter of this study,GPSR of T1 DM patients was lower than that of healthy normal group(37.71±7.31% vs.41.82±8.09%,P=0.015).Subgroup analysis showed that global and segmental strain(radial,circumferential and longitudinal)of left ventricle in children with T1 DM was not significantly different from that in healthy children(all P > 0.05).However,global and segmental longitudinal strain(GPSL:-13.82±2.41% vs.-16.31±2.34%,P=0.004;BPSL:-11.50±3.39% vs.-14.54±2.75%,P=0.007;MPSL:-12.78±2.70% vs.-15.06±2.44%,P=0.015;APSL:-17.18±1.98% vs.-19.38±3.18%,P=0.021)and GPSR(35.55±6.60% vs.41.71±7.48%,P=0.029)decreased significantly in adult patients with T1 DM.Multiple linear regression identified that left ventricular ejection fraction was linearly correlated with GPSC in patients with T1DM(β=0.611,P=0.000).ROC curve analysis was performed for further and the result showed that GPSR can differentiate subclinical systolic dysfunction in asymptomatic T1 DM patients.In the subgroup analysis,GPSR,GPSL,BPSL,MPSL and APSL could evaluate the subclinical systolic dysfunction in adult patients with T1 DM.SIpeak in the middle segment of left ventricle was positively correlated with GPSL(r=0.312,P=0.033).Conclusion:Despite without obvious complications,T1 DM patients would develop a variety of myocardial abnormalities at an early stage.T1 DM patients could develop coronary microcirculation injury which is related to left ventricular remodeling and systolic function.The most prominent microcirculation dysfunction was found in basal segment.In addition,child and adult with negative LGE may have diffuse myocardial interstitial fibrosis,which may have negative effect on left ventricular ejection function.Finally,T1 DM patients would develop subclinical left ventricular dysfunction characterized by myocardial deformation dysfunction.Myocardial deformation parameters were important imaging indicators reflecting early subclinical cardiac injury in adult patients with T1 DM.In conclusion,multimodal CMR can be used to quantitatively evaluate myocardial microcirculation disturbance,interstitial fibrosis,and myocardial deformation injury in patients with type 1 diabetes. |
