T2DM is a common risk factor for cardiovascular disease. Hyperglycemia, insulin resistance and impaired signal transductions of cardiac insulin metabolism can reduce myocardial glucose uptake, increase the production of myocardial reactive oxygen species, induce mitochondrial dysfunction, and reduce the content of ATP and Ca2+ in cardiomyocytes, which can lead to myocardial autophagy and myocardial necrosis, and impair myocardial metabolism and function.[9] In the early stage, DM can cause myocardial fibrosis and increased stiffness, leading to reduced LV diastolic filling, enlarged atrial size, and increased blood flow filling and LV end diastolic pressure; in the second stage, LV hypertrophy, cardiac remodeling, diastolic dysfunction and heart failure with normal LVEF occurred.[10] With the development of diabetic cardiomyopathy, diastolic dysfunction and cardiac compliance falling may coexist with systolic dysfunctions, leading to reduced LVEF.[11] Hyperlipidemia is a common clinical metabolic disease, characterized by an abnormal increase of lipid and lipoprotein levels,[1] which can cause myocardial hypertrophy, fibrosis, myocardial cell apoptosis, LV systolic and diastolic subclinical function damage,[12] accelerate atherosclerosis, aggravate cardiac dysfunction and cardiovascular events in T2DM patients.[13]
There was a significant difference of serum UA levels among the three studied groups. Elevated serum UA is a metabolic syndrome, which can interfere with glucose uptake, aggravate insulin resistance, inhibit the bioavailability of nitric oxide, and induce endothelial dysfunction. It is associated with the progression of T2DM,[14] and is an independent predictor of cardiovascular disease.[15] Studies have found that serum UA level increases gradiently with cardiovascular risk factors, and the possibility of atherosclerosis significantly elevated as well.[16] The levels of TC and LDL-C can affect the formation of atherosclerotic plaques, promote inflammatory reaction and oxidative stress, damage vascular wall elastin, induce the production of superoxide, and lead to atherosclerosis; besides, serum UA and cholesterol levels have a synergistic effect on the aggravation of atherosclerosis due to their overlapping mechanism.[17]
There was no significant difference in LAD, IVS, LVPW, LVDd, LVDs, LVEF, RVDd, TAPSE, E/A, E/e' and other conventional echocardiography parameters among the three groups, indicating that conventional echocardiography has limitations. Compared with the normal control and T2DM group, the longitudinal strain of LV middle segment in T2DM with hyperlipidemia group decreased, which may be related to the compensatory response of subepicardial muscle fiber torsion.[18] LV GLS in T2DM group and T2DM with hyperlipidemia group decreased compared to the normal control group, suggesting that hyperglycemia and insulin resistance can lead to cardiomyocyte hypertrophy, myocardial microvascular endothelial cell dysfunction, intercellular collagen deposition, expansion of extracellular space, and increase of myocardial stiffness and myocardial degeneration.[19] As an atherosclerotic factor, lipids can trigger the release of pro-inflammatory cytokines, promote the thickening of arterial intima and reduce myocardial blood flow.[20] Moreover, excessive lipid metabolites can easily result in myocardial fibrosis and reduced ventricular diastolic compliance and diastolic energy,[21] and thus impaired myocardial function.
RV GLS in T2DM group and T2DM with hyperlipidemia group decreased, indicating that RV function was impaired in two groups. Kang et al[22] found that DM was associated with RV systolic and diastolic dysfunction. LV diastolic and systolic dysfunction caused by T2DM may have an important influence on RV due to the ventricular interdependence. The two ventricles are combined anatomically through their muscle fiber anatomical structure and IVS, exhibiting an interdependent physiological feature,[23] which is related to the interwoven subendocardial fibers of IVS between RV and LV, indicating that diabetes inducing myocardial diffuse fibrosis can affect eccentric hypertrophy, diastolic and systolic dysfunction of the two ventricles. Due to the non-antagonistic vasoconstriction by T2DM,[22] systemic macrovascular and microvascular functions were impaired and the arterial tension was increased by causing myocardial endothelial cell dysfunction, inflammatory response, calcium homeostasis change and substrate metabolism.[24] In this study, the middle strain of LV was consistent with RV in two T2DM groups. There was no significant difference of RV GLS between T2DM group and T2DM with hyperlipidemia group, which might be due to the fact that DM and lipid treatment had been carried out for a period of time, possibly affecting the improvement of RV function and mechanics.[25]
Compared with the normal control group, LA GLS in T2DM group and T2DM with hyperlipidemia group decreased (P < 0.05), indicating that both T2DM and T2DM with hyperlipidemia groups had LA dysfunction. Hyperglycemic toxicity can cause abnormal myocardial composition, mainly due to excessive collagen accumulation,[26] resulting in increased extracellular volume of cardiomyocytes and LA fibrosis in patients with T2DM, which may be the main factor for the decrease of LA GLS. However, there was no significant difference of LV and RV GLS between T2DM and T2DM with hyperlipidemia groups, but LA GLS significantly decreased (P < 0.05), suggesting that LA GLS in T2DM with hyperlipidemia group was more sensitive than LV and RV GLS, which may have an association with dyslipidemia and BMI. Dyslipidemia aggravates myocardial injury and dysfunction by causing myocardial interstitial fibrosis, impaired calcium homeostasis, mitochondrial dysfunction and microvascular lesions.[27] The higher BMI, to a certain extent, can increase blood capacity, promote cardiac enlargement and lead to the decrease of atrial GLS.[28]
Compared with the normal control group, RA GLS in T2DM group and T2DM with hyperlipidemia group decreased; compared with T2DM group, RA GLS in T2DM with hyperlipidemia group decreased (P < 0.05), indicating that RA function was impaired in T2DM and T2DM with hyperlipidemia groups. It was found that HbA1c was independently correlated with RA GLS.[25] Bening et al have proved that diabetes had a significant impact on the RA fiber contractility, and RA contractility of diabetic patients was significantly lower than that of non-diabetic patients.[23] The sub-endocardial fibrosis of T2DM atrium leads to the decrease of the elasticity of the atrial wall, which may cause atrial enlargement and dysfunction. Blood glucose inhibits RA myofilament function by changing calcium homeostasis. Hyperlipidemia can aggravate the accumulation of myocardial lipid, result in myocardial stiffness and systolic and diastolic dysfunction. Ventricular diastolic dysfunction is an independent predictor of atrial phase function, and changes in atrial function can indicate ventricular diastolic dysfunction.[29] In this study, there was no significant difference of LV GLS and RV GLS between T2DM and T2DM with hyperlipidemia groups, while LA GLS and RA GLS significantly decreased, indicating that LA and RA function changes earlier than LV and RV, suggesting that T2DM group and T2DM with hyperlipidemia group may have ventricular diastolic dysfunction at an early stage.