Ritchie Rebecca H, Zerenturk Eser J, Prakoso Darnel, Calkin Anna C
Heart Failure PharmacologyBaker Heart & Diabetes Institute, Melbourne, Victoria, Australia.
Central Clinical SchoolMonash University, Melbourne, Victoria, Australia.
J Mol Endocrinol. 2017 May;58(4):R225-R240. doi: 10.1530/JME-16-0249. Epub 2017 Apr 3.
Diabetic cardiomyopathy was first defined over four decades ago. It was observed in small post-mortem studies of diabetic patients who suffered from concomitant heart failure despite the absence of hypertension, coronary disease or other likely causal factors, as well as in large population studies such as the Framingham Heart Study. Subsequent studies continue to demonstrate an increased incidence of heart failure in the setting of diabetes independent of established risk factors, suggesting direct effects of diabetes on the myocardium. Impairments in glucose metabolism and handling receive the majority of the blame. The role of concomitant impairments in lipid handling, particularly at the level of the myocardium, has however received much less attention. Cardiac lipid accumulation commonly occurs in the setting of type 2 diabetes and has been suggested to play a direct causal role in the development of cardiomyopathy and heart failure in a process termed as cardiac lipotoxicity. Excess lipids promote numerous pathological processes linked to the development of cardiomyopathy, including mitochondrial dysfunction and inflammation. Although somewhat underappreciated, cardiac lipotoxicity also occurs in the setting of type 1 diabetes. This phenomenon is, however, largely understudied in comparison to hyperglycaemia, which has been widely studied in this context. The current review addresses the changes in lipid metabolism occurring in the type 1 diabetic heart and how they are implicated in disease progression. Furthermore, the pathological pathways linked to cardiac lipotoxicity are discussed. Finally, we consider novel approaches for modulating lipid metabolism as a cardioprotective mechanism against cardiomyopathy and heart failure.
糖尿病性心肌病在四十多年前首次被定义。在对糖尿病患者进行的小型尸检研究中观察到了这种疾病，这些患者尽管没有高血压、冠状动脉疾病或其他可能的致病因素，但仍患有伴随的心力衰竭，在诸如弗雷明汉心脏研究等大型人群研究中也观察到了这一现象。随后的研究继续表明，在糖尿病背景下，心力衰竭的发病率增加，且与既定风险因素无关，这表明糖尿病对心肌有直接影响。葡萄糖代谢和处理受损受到了大部分指责。然而，脂质处理方面的伴随损害，尤其是在心肌水平上的损害，受到的关注要少得多。心脏脂质积累通常发生在2型糖尿病患者中，并被认为在心肌病和心力衰竭的发展过程中起着直接的因果作用，这一过程被称为心脏脂毒性。过量的脂质会引发许多与心肌病发展相关的病理过程，包括线粒体功能障碍和炎症。虽然心脏脂毒性在一定程度上未得到充分重视，但在1型糖尿病患者中也会出现。然而，与高血糖症相比，这种现象在很大程度上研究较少，而高血糖症在这方面已经得到了广泛研究。本综述探讨了1型糖尿病心脏中发生的脂质代谢变化以及它们如何与疾病进展相关。此外，还讨论了与心脏脂毒性相关的病理途径。最后，我们考虑了调节脂质代谢作为预防心肌病和心力衰竭的心脏保护机制的新方法。
