| Background and Objective:Type 2 diabetes mellitus(T2DM),obesity,and hypertension are common coexisting chronic conditions that are associated with an increased overall risk of premature death due to systemic complications,of which cardiovascular disease is the primary complication and leading cause of death.Diabetes mellitus related cardiomyopathy has recently been described as a distinct progression of left ventricular(LV)systolic and diastolic dysfunction.Pathological changes in the myocardium may explain the development of two different phenotypes.Evidence from several experimental studies indicates that partial common pathological mechanism is involved in both T2DM,obesity and hypertension related cardiac damage.However,the relationship among mechanism,disorder,and function are not completely understood and is difficult to quantify.Previous studies have confirmed the effect of T2DM,obesity or hypertension alone on cardiac structure and function,while few studies have studied the combined effect of obesity/hypertension in the context of T2DM based on cardiac geometry,microcirculation perfusion,tissue characteristics and cardiac function.Cardiac magnetic resonance imaging(CMR)has the advantages of multi-parameter and multi sequence.Based on post-processing software,it can " one-stop-shop "quantitative or semi-quantitative evaluation of cardiac morphology,structure,function and myocardial tissue characteristics,plays a very important role in the diagnosis and prognosis of various cardiomyopathy,and provides a feasible technique for noninvasively evaluating the pathophysiological changes of myocardial tissue,cardiac structure and cardiac function and the additive effects among T2DM,obesity,and hypertension.Therefore,this study aims1)Part one:To evaluate changes of LV geometry,myocardial microcirculation,tissue characteristics,and systolic and diastolic functions in T2DM patients using multi sequence CMR imaging,and to investigate the effects of LV structure,myocardial microcirculation,and tissue characteristics on LV systolic and diastolic functions in patients with T2DM;2)Part two:To investigate the effect of obesity on myocardial microcirculation in T2DM patients using CMR first-pass perfusion imaging;3)Part three:To investigate the effects of hypertension on LV structure,myocardial microcirculation,tissue characteristics,and systolic and diastolic functions in T2DM patients using multisequence CMR imaging.Materials and Methods:Between April 2016 and April 2019,T2DM patients who were clinically confirmed by the department of Endocrinology and Metabolism of our hospital and prospectively examined by multiparametric CMR were enrolled in this study.At the same time,the study prospectively or from the hospital database included healthy control group matched with the T2DM group in gender,age and body mass index(BMI)for analysis.CMR-derived parameters including LV remodeling index,upslope,time to maximum signal intensity(TTM),Max Signal Intensity(Max SI)、perfusion index(PI),extracellular volume(ECV),myocardial T2 value,and peak strain(PS),peak systolic strain rate(PSSR),and peak diastolic strain rate(PDSR)in radial,circumferential,and longitudinal directions,were analyzed and compared between T2DM patients and controls.Based on clinical and CMR parameters and inclusion and exclusion criteria of participants,In the first part of the study,we prospectively enrolled 138 T2DM patients and 42 controls to evaluate the effects of CMR parameters and clinical variables on LV systolic and diastolic function using univariable and multivariable backward linear regression analyses;In the second part,136 patients with T2DM were prospectively enrolled and divided into normal weight(BMI=18.0-22.9 kg/m2;n=61),overweight(BMI=23.0-24.9 kg/m2;n=33),and obese subgroups(BMI>25 kg/m2;n=42)according to the World Health Organization’s definition for Asian individuals,and 79 controls(33,27 and 19 normal weight,overweight and obese individuals,respectively)were included in the study for statistical analysis.Univariable and multivariable backward linear regression and logistic regression analyses were used to evaluate the potential additive effect of obesity on microvascular dysfunction in T2DM individuals;In the third part,138 patients with T2DM were prospectively enrolled and divided into 80 patients with normotensive T2DM(T2DM[HT-])and 58 patients with hypertensive T2DM(T2DM[HT+])according to the presence or absence of hypertension.Meanwhile,42 controls were included in the study for statistical analysis.Univariable and multivariable backward linear regression analyses were used to evaluate the potential additive effect of hypertension on LV systolic and diastolic function in patients with T2DM.Results:In the first part of the study,compared with controls,T2DM patients showed higher LV remodeling index(0.78 ± 0.21 g/ml vs.0.60 ± 0.17 g/ml,P<0.001),lower PI(0.11 ± 0.04 vs.0.14 ± 0.03,P=0.001),and increased myocardial ECV(32.26 ±4.52%vs.27.14 ± 3.97%,P<0.001),increased myocardial T2 value(42.00 ± 3.54 ms vs.39.92 ± 3.11 ms,P=0.004),decreased LV strain(PS-Radial,32.35 ± 8.73%vs.39.87 ± 9.45%,P<0.001;PS-Circumferential,-19.73 ± 3.84%vs.-20.82 ±3.12%,P=0.045;PS-Longitudinal,-12.52 ± 3.42%vs.-15.91 ± 3.62%,P<0.001).The univariable and multivariable analysis of systolic and diastolic function revealed,in LV systolic model,the microvascular PI was related to cardiac systolic function in all three directions(PSSR-Radial,β=0.249,P=0.005;PSSR-Circumferential,β=-0.233,P=0.001;PSSR-Longitudinal,β=-0.317,P<0.001),and the myocardial T2 value was correlated with LV PSSR-Longitudinal(β=0.304,P=0.002).In diastolic model,the LV remodeling index was related to cardiac systolic function in all three directions(PDSR-Radial,β=0.172,P=0.036;PDSR-Circumferential,β=-0.197,P=0.032;PDSR-Longitudinal,β=-0.361,P<0.001),whereas the PI,T2 value,and ECV were more likely to affect cardiac diastolic function in longitudinal level(PI:PDSR-Longitudinal,β=0.203,P=0.004;T2 value:PDSR-Longitudinal,β=-0.252,P<0.001;ECV:PDSR-Longitudinal,β=-0.194,P=0.026).In the second part,when T2DM and obesity coexist,compared with controls with comparable BMIs,patients with T2DM showed reduced Upslope and Max SI and increased TTM.For both T2DM and control subgroups,perfusion function gradually declined with increasing BMI,which was confirmed by all perfusion parameters,except for TTM(all P<0.01),the PDSR-Circumferential gradually decreased with increasing BMI(P<0.05),while other strain parameters showed no significant change trend with the change of BMI.The multivariable analysis model(R2=0.542)showed that female sex had a positive microcirculation effect(β=0.303,95%Confidence interval[CI],0.201 to 0.443,P<0.001)and that higher BMI(β=-0.421,95%CI,-0.607 to-0.327,P<0.001),longer diabetes duration(β=-0.185,95%CI,-0.334 to-0.073;P=0.006)and higher HbA1c(β=-0.171;95%CI,-0.252 to-0.033;P=0.023)had a negative microcirculation effect.The multivariable logistic regression analysis indicated that T2DM was an independent predictor of microvascular dysfunction in normal weight(Odds ratio[OR],3.6;95%CI,1.39 to 9.41;P=0.002),overweight(OR,6.85;95%CI,1.74 t o26.97;P=0.005)and obese participants(OR,7.19;95%CI,1.89 to 27.35;P=0.003)and that the OR increased with increasing BMI.In the third part,when T2DM and hypertension coexist,from controls,through patients with T2DM without coexisting hypertension,to patients with T2DM and hypertension,the LV remodeling index progressively and significantly increased(control group vs.T2DM[HT-]vs.T2DM[HT+],0.64 ± 0.03 g/ml vs.0.72 ±0.02 g/ml vs.0.83 ± 0.02 g/ml,P<0.001),ECV progressively increased(control group vs.T2DM[HT-]vs.T2DM[HT+]group,27.08±1.32%vs.31.24±0.81%vs.32.41 ± 1.02%,P=0.008)and LV radial,circumferential,and longitudinal strains progressively decreased(control group vs.T2DM[HT-]vs.T2DM[HT+],PS-Radial,40.87 ± 1.45%vs.34.80 ± 0.98%vs.28.94 ± 1.22%,P<0.001;PS-Circumferential,-20.75 ± 0.61%vs.-20.21 ± 0.41%vs.-19.27 ± 0.51%,P=0.179;PS-Longitudinal:-15.91 ± 0.56%vs.-13.42 ± 0.38%vs.-11.38 ± 0.47%,P<0.001).The multivariable analysis revealed that PI and ECV were found to be correlated with both systolic(LV PSSR-Longitudinal:2.80 1/s increase per 1 unit increase in PI;0.29 1/s decrease per 10 units increase in ECV,both P<0.001)and diastolic functions(PDSR-Longitudinal:2.80 1/s increase per 1 unit increase in PI;0.33 1/s decrease per 10 units increase in ECV,both P<0.001),whereas the LV remodeling index was mainly associated with LV diastolic functions(PDSR-Longitudinal:0.83 1/s decrease per lg/ml increase in LV remodeling index,P<0.001)and the LV T2 value was mainly associated with LV systolic functions(PSSR-Longitudinal:0.30 1/s decrease per 10 units increase in LV T2 value,P=0.012).When hypertension and diabetes were entered together and adjusted for clinical and CMR-derived variables in the final multivariable model,the coexistence of hypertension in diabetes was found to be associated with increased impairment of diastolic function(P=0.015)but has little effect on systolic function(P=0.413),independent of clinical factors and CMR-derived myocardial disorder.Conclusions:T2DM patients,even those without any clinical symptoms of cardiovascular diseas,presented with LV myocardial concentric remodeling,microvascular injury,myocardial fibrosis,myocardial edema,and deformation dysfunction.The disturbance in structure,tissue,and microcirculation of the heart demonstrated diverse effects on cardiac systolic and diastolic function in T2DM patients,indicating LV concentric remodeling and increased fibrosis tended to affect diastolic function,and myocardial perfusion function and edema corresponded with both systolic and diastolic function.When T2DM and obesity coexist,myocardial microvascular function gradually declined with increasing BMI in both diabetes and non-diabetes status.T2DM was associated with an increased risk of microvascular dysfunction,and obesity exacerbated the risk of microvascular dysfunction of T2DM.When T2DM and hypertension coexist,hypertension in the context of diabetes is significantly associated with LV diastolic function and concentric remodeling;however,it has little effect on systolic function,myocardial microcirculation,or fibrosis independent of covariates. |
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