The Cardiac Structure And Function Changes In Patients Of Abdominal Obesity With Type 2 Diabetes

Objective: Diabetic heart disease is one of the major cause of death in diabetic patients, including diabetic coronary heart disease, diabetic cardiomyopathy and diabetic autonomic neuropathy. Coronary atherosclerotic heart disease, namely coronary heart disease, has been known clinically. Diabetic cardiomyopathy (DCM) is one of the major microvascular complications for diabetic (DM). The pathogenesis of diabetic cardiomyopathy is related with myocardial cell metabolism (energy substrates supply and use unusual, hyperinsulinemia and insulin resistance), changes in cardiac electrophysiology, endothelial dysfunction and microvascular disease (inflammation and oxidative stress, renal hormone angiotensin system activation), and cardiac autonomic neuropathy and so on. Obesity is a high risk of type 2 diabetes,and in these people obese adipose tissue releases a large number of non-esterified fatty acids, glycerol, fat-derived cytokines (such as leptin, adiponectin, resistin, retinol binding protein, etc.), inflammatory cytokines (such as transforming growth factorα, interleukin-6, monocyte chemoattractant protein 1, etc.), which are involved in insulin resistance. By way of increasing hemodynamic burden ,activating the sympathetic activity, aggravating oxidative stress and inflammation, lipid toxicity leaded by fat accumulation, the overweight or obese caused myocardial damage. Adipocytokine secretion imbalance and/or dysfunction play an important role in the process in insulin resistance and the pathophysiology of cardiovascular disease,which is regarded as the possible intermediate links of insulin resistance and cardio diseases. Adiponectin (APN) is the only fat-derived cytokines with protective effect recently discovered, APN may through activation of CAMP protein kinase pathway to directly regulate glucose and lipid metabolism and insulin sensitivity, enhance the ability of insulin regulation of blood sugar in vivo, thereby reducing blood sugar levels. APN is a potentin insulin promoter linking glucose and lipid metabolism.Adiponectin may also change the state of myocardial oxidative stress, thus reducing the myocardial fibrosis and improve cardiac function, as a protective factor in diabetic cardiomyopathy. Retinol binding protein 4 (RBP4) as a new adipocytokine, plays an important role in signal transduction of insulin. RBP4 levels lifted, IRS1 tyrosine phosphorylation decreased, PI3K activity decreased, result in impaired insulin receptor signaling, decreased GLUT4 expression, which affects the glucose utilization by liver, muscle tissue, while accelerating the adipose tissue lipolysis, causes the body lipid disorders. Many studies domestic and abroad report that RBP4 is closely related to and insulin resistance and in obesity, especially in abdominal obesity there were significantly higher levels of serum RBP4 and RBP4 mRNA expression increased. Echocardiography is currently the most commonly used methods in clinical for evaluation of cardiac structure and function in patients with T2DM. In the structure, glycoprotein, plastic fiber, cholesterol deposition, and myocardial interstitial inflammatory cell infiltration and fibrosis can cause left ventricular hypertrophy and ventricular weight increase and other changes, may be shown as different in myocardial thickness, heterogeneous echo, myocardial density increase. Changes in diastolic function mainly are diastolic flow velocity decreased in the early, increased diastolic flow velocity in the late, isovolumic relaxation period extended, VE/VA and the e/a ratio decreased, left ventricular end diastolic pressure increased and end-diastolic diameter extend , mitral valve open slightly slower and open insufficiency, ventricular dysfunction flaccid, resulting in inadequate left ventricular filling before atrial contraction, (E peak reduction), A peak increase, A/E ratio increases and so on.Pathogenesis of diabetic heart diseas is complex, still not fully understood. patients with diabetes is difficult to directly obtained the pathological basis of diabetic heart disease in Clinical, so it is often difficult to diagnose such a heartillness. Therefore, this study was to measure the intra-abdominal fat area by CT, Observed in cardiac structure and function changes in intra-abdominal obesity patients with T2DM patients, analysis relationship of intra-abdominal obesity and RBP4, APN level, Explore the possible pathogenesis of diabetic heart disease. Expect to provide the basis of the prevention, forecasting, and therapy for diabetic heart diseas.Methods: Select 198 type 2 diabetic patients according to The inclusion and exclusion criteria, which were in the third hospital of Hebei Medical University, department of Endocrinology from September 2009 to September 2010. All patients holding breath supine under a multi-breath-hold helical CT for single-level cross-sectional scanning along umbilical plane. to measure intra-abdominal fat area (VA), subcutaneous fat area (SA), calculation of intra-abdominal fat area / subcutaneous fat area ratio (VA/SA). Type of non-abdominal obesity (VA≤100cm2) as the control group (A group), a total of 34 patients (18 males and 16 females), mean age (55.76±10.62) years. Abdominal obesity in 164 patients with type 2 diabetes, according to the median of abdominal fat area divided into two groups according to the median (B, C group), B group 82 patients (38 male, female 44 cases), mean age (56.03±8.35) years; C group 82 patients (male 45, female 37 cases), mean age (57.26±10.37) years. The clinical data of subjects is collected: Record the basic information, including gender, Age (Age), marriage, nationality, occupation, duration of disease, family history, personal history (diet, living habits, smoking, drinking, etc.), past medical history (coronary heart disease, history of hypertension and other diseases), measure waist circumference, hip circumference, height, weight, blood pressure, calculate waist-hip ratio, body mass index (BMI). Early morning fasting blood taken fasting blood glucose (FBG), cholesterol (TC), three ester triglyceride (TG), high density lipoprotein - cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), fasting insulin (Fins), fasting C peptide. The homeostasis model assessment 1 to calculate insulin resistance index (HOMA-IR), the formula: HOMA-IR = FBG×Fins/22.5.Lycosylated hemoglobin (HbA1c), urinary A/Cr value measured by glycosylated hemoglobin gs. After centrifugation, the upper venous blood serum placed in -80℃refrigerator spare frozen, unified the serum concentration of retinol binding protein 4 (RBP4), adiponectin (APN) by ELISA assay. The three groups be measured cardiac structure and function index by echocardiography. By Devereux method, LVM = 1.04×[(IVS + LV + PWTd)~3-LV~3]-13.6, calculat left ventricular mass (LVM). All statistical used SPSS13.0 software done, p<0.05 (two-sided test) for the difference was statistically significant. Measurement data of each group were tested for normality, normal variables distributed as x±s, non-normally distributed variables as median (interquartile range) ,the count data used (%).Normal variables and variables coincidencing the normal distribution after logarithmic transformation, compared among groups using single factor analysis of variance (one-way ANOVA), with SNK pairwise comparison method (homogeneity of variance) or Dunnett's T3 (Heterogeneity of variance .) Count data using chi-square test. Correlation between each factor use a simple correlation and regression analysis, using Pearson correlation coefficient describes the correlation strength. Multiple linear stepwise regression analysis tests the the relationship between intra-abdominal fat area, RBP4, APN and left ventricular mass, excluding the effect of other factors. Logistic regression analysis predicts intra-abdominal fat area increase in the risk of left ventricular diastolic dysfunction.selecting and exclusion criteria of multivariate linear stepwise regression and Logistic regression analysis were respectively as 0.05 and 0.10.Results:1 The age, disease duration, smoking, diastolic blood pressure, glycosylated hemoglobin was no significant difference in three groups. WC, WHR, SBP, VA, SA, TC, HDL, LDL-C, FPG, RBP4, APN difference was statistically significant (p<0.05 or p<0.01) in three groups. including WC, WHR, SBP, VA, SA, TC, TG, LDL-C, FPG, RBP4 were lower in groups A than B, C group. HDL-C, APN levels in A group for the high level of expression than B, C groups. Compared with A group, BMI, V/S, urinary A/Cr was significantly increased in group B, C. But there were no significant difference between the B and C group. Compared with the B group, C group Fins increased (p <0.05).2 The control group (A group) compared to intra-abdominal obesity group (B, C group) , the LV, IVS, LVPW, LVM, EF, Peak E, A difference was significant (p<0.05 or p<0.01 ), where LV, LVPW, LVM, Peak E, Peak E / A <1 the ratio in the B, C group still has a significant difference (p<0.05 or p<0.01), while the IVS, EF (%), Peak A differences was not statistically significant between the two ventral obesity groups.3 The result of simple linear correlation analysis for APN and RBP4 expression level, showed that the expression level of APN with WC, WHR, VA, SA, V/S, TG, LDL were significantly negative correlation (r values were -0.49,-0.35,-0.56,-0.40,-0.47,-0.53,-0.32), APN expression level showed moderate intensity correlation to WC, VA, and TG. There were a linear correlation in varying degrees between WC, VA, SA, V/S ,TG and RBP4(P<0.01), which the strongest intensity correlation was VA (r=0.36). BMI, TC, HDL had no linear relationships with APN and RBP4.4 The course, WC,WHR,VA,SA,V/S,TG,HDL-C,FPG,ln(HOMA-IR), APN,RBP4 all have correlations to LVM in varying degrees (r values were 0.35, 0.26, 0.13, 0.39, 0.22, 0.23, 0.12, -0.24, 0.28, 0.45, -0.30, 0.21), with statistical significance (P<0.05). After controlling for confounding factors, partial correlation analysis showed WC, WHR, VA, ln (HOMA-IR), APN and RBP4 are still relevant with the LVM. Multiple stepwise linear correlation analysis studys the effects related to LVM changing. After strict control for confounding factors and interactions, multiple stepwise linear correlation analysis showed that ln (HOMA-IR), APN, RBP4, VA were independently associated factors with elevated LVM, which ln (HOMA-IR) was the largest contribution to the dependent variable, followed by intra-abdominal fat area . Logistic regression analysis (both inclusion and exclusion criteria 0.05 and respection 0.10,), showed that dyslipidemia (β=1.422, P=0.041), central obesity (β=0.847, P=0.034), APN (β=-0.901, P=0.006) entered the regression equation, the equation was statistically significant (x=20.531, P=0.000). Dyslipidemia contrasts Normal lipid,the ratio for occurrence of left ventricular diastolic dysfunction (E/A<1) is 1.422. The occurrence probability of left ventricular diastolic dysfunction significantly increased in patients with intra-abdominal obesity .Conclusion:1 Abdominal obesity can affect glucose and lipid metabolism, cause insulin resistance, to result in heart structural and functional changes, changes of left ventricular diastolic function and myocardial hypertrophy may appear precede in left ventricular systolic dysfunction.2 Adiponectin increased insulin sensitivity and improved insulin resistance, regulated lipid metabolism, it can resist to left ventricular mass increasing, reduce the risk of left ventricular diastolic dysfunction.3 Intra-abdominal fat accumulation elevated RBP4 expression level. Lower RBP4 levels can improve insulin resistance, increase insulin sensitivity.4 CT measured abdominal fat area with features of non-invasive, high accuracy and good reproducibility, can be as an assessment method for abdominal obesit, better than BMI and WC.