Diabetic cardiomyopathy-fact or fiction?
Diabetic cardiomyopathy-fact or fiction?
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DOI：
10.1007/s00059-011-3429-4
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发表时间：
2011-03-01
期刊：
影响因子：
1.7
通讯作者：
Pankuweit, S.
中科院分区：
文献类型：
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作者：
Maisch, B.;Alter, P.;Pankuweit, S.
流行病学和临床研究证实了糖尿病和心力衰竭之间的密切联系。然而，糖尿病心肌病(DCM)仍然是一个知之甚少的“实体”，有几个致病因素在糖尿病的不同阶段导致独特的临床表型。高血糖、胰岛素抵抗、肾素-血管紧张素-醛固酮系统(RAAS)激活、钙稳态改变以及晚期糖基化终产物(AGE)形成、肥厚和纤维化导致的从天然胶原网络到更硬的基质的结构变化，是糖尿病患者各自的临床表型。我们建议对糖尿病患者的心肌病变进行如下分类：(A)糖尿病患者中舒张性心力衰竭伴正常射血分数(HFNEF)，通常合并肥厚但无相关高血压。相关的冠状动脉疾病(CAD)、瓣膜疾病和未控制的高血压不存在。这被称为第1阶段DCM。(B)糖尿病患者的收缩和舒张期心力衰竭伴扩张和射血减少(HFREF)，不包括相关的CAD、瓣膜疾病和无法控制的高血压作为第2阶段DCM。(C)有小血管病变(微血管疾病)和/或微生物感染和/或炎症和/或高血压但没有CAD的糖尿病患者的收缩和/或舒张期心力衰竭为第3阶段DCM。(D)如果心力衰竭除了第3阶段DCM外还可能归因于梗塞或缺血和重塑，则术语应称为糖尿病或第4阶段DCM的心力衰竭。这些糖尿病心肌病的临床表型可以通过生物标志物、非侵入性(超声心动图、心脏磁共振成像)和有创性成像(左心、冠状动脉造影术)，并通过心内膜心肌活检进一步分析伴随的病毒感染。需要在每个患者中单独确定特定的糖尿病驱动因素对临床表型、大血管和微血管病变以及伴随的危险因素或混杂因素的作用，例如高血压、自身免疫因素或伴随或不伴随病毒持续存在的炎症。因此，高血糖、高胰岛素血症、胰岛素抵抗以及游离脂肪酸(FFAs)的脂毒性是糖尿病心肌病的致病因素。在1期和2期DCM中，糖尿病心肌病显然是事实。然而，准确地确定各种潜在的致病过程在多大程度上对整体心力衰竭表型负责仍然是一个虚构的问题。
Epidemiologic as well as clinical studies confirm the close link between diabetes mellitus and heart failure. Diabetic cardiomyopathy (DCM) is still a poorly understood "entity", however, with several contributing pathogenetic factors which lead in different stages of diabetes to characteristic clinical phenotypes. Hyperglycemia with a shift from glucose metabolism to increased beta-oxidation and consecutive free fatty acid damage (lipotoxicity) to the myocardium, insulin resistance, renin-angiotensin-aldosterone system (RAAS) activation, altered calcium homeostasis and structural changes from the natural collagen network to a stiffer matrix due to advanced glycation endproduct (AGE) formation, hypertrophy and fibrosis contribute to the respective clinical phenotypes of DCM.We propose the following classification of cardiomyopathy in diabetic patients:(a) Diastolic heart failure with normal ejection fraction (HFNEF) in diabetic patients often associated with hypertrophy without relevant hypertension. Relevant coronary artery disease (CAD), valvular disease and uncontrolled hypertension are not present. This is referred to as stage 1 DCM.(b) Systolic and diastolic heart failure with dilatation and reduced ejection (HFREF) in diabetic patients excluding relevant CAD, valvular disease and uncontrolled hypertension as stage 2 DCM.(c) Systolic and/or diastolic heart failure in diabetic patients with small vessel disease (microvascular disease) and/or microbial infection and/or inflammation and/or hypertension but without CAD as stage 3 DCM.(d) If heart failure may also be attributed to infarction or ischemia and remodeling in addition to stage 3 DCM the term should be heart failure in diabetes or stage 4 DCM.These clinical phenotypes of diabetic cardiomyopathy can be separated by biomarkers, non-invasive (echocardiography, cardiac magnetic resonance imaging) and invasive imaging methods (levocardiography, coronary angiography) and further analysed by endomyocardial biopsy for concomitant viral infection. The role of specific diabetic drivers to the clinical phenotypes, to macro- and microangiopathy as well as accompanying risk factors or confounders, e.g. hypertension, autoimmune factors or inflammation with or without viral persistence, need to be identified in each individual patient separately. Thus hyperglycemia, hyperinsulinemia and insulin resistance as well as lipotoxicity by free fatty acids (FFAs) are the factors responsible for diabetic cardiomyopathy. In stage 1 and 2 DCM diabetic cardiomyopathy is clearly a fact. However, precise determination of to what degree the various underlying pathogenetic processes are responsible for the overall heart failure phenotype remains a fiction.