| BackgroundHeart failure(HF)is a complex clinical syndrome caused by systolic and diasolatic dysfunction for a variety of causes,resulting in abnormal cardiac structural function.Because of its high mortality and rehospitalization rate,it becomes the last two battlefields in the cardiovascular field in the 21st century accompanied with atrial fibrillation.Type 2 diabetes mellitus(T2DM)is an independent risk factor for heart failure.About 30%to 40%of patients with HF have T2DM.T2DM worsens the clinical status of HF patients and increases all-cause mortality and cardiovascular mortality.Moreover,HF is also an independent predictor of clinical prognosis in patients with T2DM.Because existing randomized controlled trial do not support that intensive glycemic control can reduce the incidence of heart failure in diabetics,which suggesting some unique clinical features and pathophysiological mechanisms in diabetics with HF.Myocardial steatosis and myocardial fibrosis is mainly diabetes-associated cardiac structural characteristics.It is mainly characterized by left ventricular concentric remodeling and left ventricular hypertrophy on imaging changes.Left ventricular hypertrophy and myocardial fibrosis play the important role in the occurrence and progression of heart failure.Previous studies have suggested that excretion of urinary albumin reflected not only localized renal disease,but was a marker of generalized endothelial dysfunction.Even if the urinary albumin-creatinine ratio(UACR)was within the normal range,the level of UACR associated with the risk of cardiovascular events.Transforming growth factor-β1(TGF-β1)is one of the common mediators of myocardial fibrosis caused by many causes.Although a large number of experiments have shown that the expression of TGF-β1 in cardiomyocytes and tissues is significantly increased in myocardial fibrosis,the results of studies on the associations between plasma TGF-β1 levels and HF patients are not consistent,and its clinical significance is inconclusive.This study was to investigate the associations between diabetic patients with left ventricular hypertrophy and UACR level within normal range,which might identify and intervene subclinical cardiac structural changes in diabetic patients;to investigate the changes and clinical significance of plasma TGF-β1 levels in diabetics with heart failure.Chapter 1 Clinical features of type 2 diabetic patients with left ventricular hypertrophy and chronic heart failureObject To analyze the changes of insulin resistance in Type 2 diabetic patients with left ventricular hypertrophy and chornic heart failure,and to investigate the correlation between insulin resistance and other clinical indicators.Methods A total of 520 type 2 diabetic patients admitted to the department of endocrinology in our hospital from June 2016 to June 2018 were selected.The clinical data were collected in the electronic medical records system.Results(1)Among 520 diabetics,UACR was significantly higher in patients with heart failure than those without heart failure[1733.0(181.5-2601.5)vs 11.5(5.3-58.4)mg/g,P<0.001].Compared with non-HF group,the prevalence of left ventricular hypertrophy in HF patients,mostly concentric hypertrophy,was significantly higher(53.1 vs 23.2%,P<0.001).(2)Among the 520 diabetics,there were more women(62.1 vs 33.9%,P<0.001),more obesity(22.1 vs 10.8%,P=0.001)and higher UACR[55.3(13.5-444.7)vs 9.7(5.3-68.1)mg/g,P<0.001]in left ventricular hypertrophy group.There was no significantly difference in insulin resistance[1.47(0.67-2.92)vs 1.45(0.68-3.38),P=0.879].(3)The insulin resistance index was negatively correlated with serum NT-proBNP(r=-0.242,P<0.001),and positively correlated with BMI(r=0.242,P<0.001).Excluding heart failure patients,insulin resistance index was negatively correlated with NT-proBNP(r=-0.250,P=0.002)and positively correlated with BMI(r=0.257,P=0.001).Conclusion(1)UACR in diabetic with CHF is significantly higher that non-CHF patients,but the insulin resistance is lower.(2)UACR in diabetic with left ventricular hypertrophy is significantly higher than non-LVH patients,but there is no significantly difference in insulin resistance.(3)Serum NT-proBNP level is negatively correlated with insulin resistance index in diabetics,positively with BMI.Serum BNP may have an effect of reducing insulin resistance.Chapter 2 Predictive value of UACR in the normal range for type 2 diabetic patients with left ventricular hypertrophyObject To compare the prevalence of left ventricular hypertrophy of diffetent UACR in the normal range,and to analyze the predictive value and optimal cut-off point of UACR for diabetic with left ventricular hypertrophy.Methods A total of 317 type 2 diabetics with UACR within normal UACR(<30 mg/g)were enrolled.The clinical data was collected in the electronic records.The patients is categorized by UACR quartiles.There were 102 cases in UACR quartile 1(UACR<4.4mg/g),56 cases in quartile 2(4.4mg/g<UACR≤7.1mg/g),80 cases in quartile 3(7.1mg/g<UACR≤12.4mg/g),and 79 cases in quartile 4(12.4mg/g<UACR<30 mg/g).Results(1)From UACR quartile 1 to quartile 4,the prevalence of left ventricular hypertrophy increased(10.8 vs 16.1 vs 16.3 vs 36.7%,P<0.001),the proportion of female patients(22.5 vs 41.1 vs 48.8 vs 50.6%,P<0.001),the prevalence of hypertension increased significantly(27.5 vs 30.4 vs 33.8 vs 59.5%,P<0.001).(2)Multiple linear regression showed that UACR was significantly and independently correlated with HbAlc(b=0.027,P<0.001),hypertension(b=0.156,P<0.001),ALB(b=-0.011,P=0.003)and gender(b=0.072,P=0.039).(3)To evaluate the predict performance of UACR for left ventricular hypertrophy,The AUC in ROC curve was 0.682[95%CI(0.602-0.760),P<0.001].The best diagnostic cut-off point was 10.2mg/g,the sensitivity was 61.3%,and the specificity was 74.9%.According to the prevalence of left ventricular hypertrophy in diabetics with normal UACR in this study,the positive predictive value was 75.2%.The negative predictive value was 88.8%.(4)Logistic regression analysis showed that age,gender,hypertension,1g UACR,obesity were significantly associated with left ventricular hypertrophy.In contrast to subjects in UACR<10.2mg/g(the optimal cut-off point according to ROC curve),the OR for for left ventricular hypertrophy was[3.413,95%CI(1.753-6.644),P<0.001]in UACR>10.2mg/g after adjusted for the confounding factors including age,gender and obesity.Further adjusted for hypertension,smokes and carotid plaque,the OR was[3.100,95%CI(1.558-6.167),P=0.001]Conclusion(1)The increase of UACR in the normal range is independently related to the increase of HbAlc,indepent of hypertension,gender,age,smoking and ALB.(2)The increase of UACR in the normal range is independently related to left ventricular hypertrophy.The optimal cut-off point of UACR for predicting left ventricular hypertrophy is 10.2mg/g.(3)In contrast to subjects in UACR<10.2mg/g,UACR≥10.2mg/g is independently associated with left ventricular hypertrophy,after adjusted for age,gender,and obesity.Further adjusted for hypertension,smokes and carotid plaque,it is still independenly associated with left ventricular hypertrophy.It may be more reasonable to take UACR=10mg/g as a cut-off point for screening subclinical cardiac structural changes in diabetic.Chatper 3 The plasma TGF-β1 levels in type 2 diabetic patients with acute heart failure not caused by acute coronary syndromeObject To analyze the plasma TGF-β1 level in type 2 diabetics with heart failure not caused by acute coronary syndrome and its possible causes.Methods From December 2017 to May 2018,a total of 179 type 2 diabetic patients who presented with symptoms of dyspnea in the department of cardiology of our hospital were enrolled.The general clinical data and other relevanti ndicators were collected.The plasma TGF-β1 levels and echocardiographic parameters were measured.Results(1)Compared to the non-AHF group,there is higher plasma TGF-β1 levels[1759.5(1053.3-3586.2)vs 1002.1(732.2-1499.5)pg/mL,P<0.001],higher prevalence of left ventricular hypertrophy(75.7 vs 42.2%,P<0.001),higher prevalence of segmental wall motion disorder(51.3 vs 6.3%,P<0.001)in AHF group.(2)The patientis were categorized by the plasma TGF-β1 median.Compared with the lower TGF-β1 group,there was higher prevalence of segmental wall motion disorder(46.1 vs 24.4%,P-0.002),higher prevalence of left ventricular hypertrophy(71.9 vs 55.6%,P=0.023)in higher TGF-β1 group.(3)To evaluate the predict performance of plasma TGF-β1 for left ventricular hypertrophy and segmental wall motion disorder,The area under the ROC curve showed that plasma TGF-β1 level had no predictive value for diabetic with left ventricular hypertrophy(P=0.092),and had certain predictive ability for segmental wall motion disorder[AUC=0.648,95%CI(0.565-0.731),P=0.001).(4)Logistic regression analysis showed that plasma NT-proBNP,TGF-(31,and the use of MRA were independently correlated with heart failure.Even with the same serum NT-proBNP level,the increase of plasma TGF-β1 was highly associated with heart failure,with adjustment of ALB,the use of loop diuretic and MRA,and the OR value was[1.808,95%CI(1.162-2.813),P=0.009].The area under the ROC curve of plasma TGF-β1 to T2DM with acute heart failure:AUC=[0.682,95%CI(0.602-0.763),P<0.001]Conclusion(1)Compared with non-AHF group,there is significantly higher plasma TGF-β1 level in T2DM patients with acute heart failure.(2)Compared with lower TGF-β1 group,there is higher prevalence of segmental wall motion disorder in higher TGF-β1 group.The increased expression of TGF-β1 induced by myocardial necrosis may be related to the increased plasma TGF-β1 in T2DM patients with heart failure.(3)Plasma TGF-β1 level has certain diagnostic efficacy for diabetic patients with wall motion disorder.(4)Plasma TGF-β1 levels are independently associated with type 2 diabetic patients with acute heart failure,independent of NT-proBNP levels,suggesting that increased plasma TGF-β1 levels in heart failure have different mechanisms,compared with NT-proBNP. |
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