Department of Internal Medicine IV and Institute of Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University Hospital Tübingen, Tübingen, Germany; German Center for Diabetes Research, Neuherberg, Germany.
Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA.
Lancet Diabetes Endocrinol. 2022 Apr;10(4):284-296. doi: 10.1016/S2213-8587(22)00003-1. Epub 2022 Feb 17.
Non-alcoholic fatty liver disease (NAFLD) has become an epidemic, much like other non-communicable diseases (NCDs), such as cancer, obesity, diabetes, and cardiovascular disease. The pathophysiology of NAFLD, particularly involving insulin resistance and subclinical inflammation, is not only closely linked to that of those NCDs but also to a severe course of the communicable disease COVID-19. Genetics alone cannot explain the large increase in the prevalence of NAFLD during the past 2 decades and the increase that is projected for the next decades. Impairment of glucose and lipid metabolic pathways, which has been propelled by the worldwide increase in the prevalence of obesity and type 2 diabetes, is most likely behind the increase in people with NAFLD. As the prevalence of NAFLD varies among subgroups of patients with diabetes and prediabetes identified by cluster analyses, stratification of people with diabetes and prediabetes by major pathological mechanistic pathways might improve the diagnosis of NAFLD and prediction of its progression. In this Review, we aim to understand how diabetes can affect the development of hepatic steatosis and its progression to advanced liver damage. First, we emphasise the extent to which NAFLD and diabetes jointly occur worldwide. Second, we address the major mechanisms that are involved in the pathogenesis of NAFLD and type 2 diabetes, and we discuss whether these mechanisms place NAFLD in an important position to better understand the pathogenesis of NCDs and communicable diseases, such as COVID-19. Third, we address whether this knowledge can be used for personalised treatment of NAFLD in the future. Finally, we discuss the current treatment strategies for people with type 2 diabetes and their effectiveness in treating the spectrum of hepatic diseases from simple steatosis to non-alcoholic steatohepatitis and hepatic fibrosis.
非酒精性脂肪性肝病（NAFLD）已成为一种流行疾病，与其他非传染性疾病（NCD）如癌症、肥胖、糖尿病和心血管疾病类似。NAFLD 的病理生理学，特别是涉及胰岛素抵抗和亚临床炎症的病理生理学，不仅与这些 NCD 密切相关，而且与传染性疾病 COVID-19 的严重病程也密切相关。仅遗传因素无法解释过去 20 年来 NAFLD 患病率的大幅增加，也无法解释未来几十年预计的增加。由于肥胖和 2 型糖尿病在全球范围内的流行，导致葡萄糖和脂质代谢途径受损，这很可能是导致 NAFLD 患者增加的原因。由于通过聚类分析确定的糖尿病和糖尿病前期患者亚组中 NAFLD 的患病率不同，因此根据主要病理机制途径对糖尿病和糖尿病前期患者进行分层可能会改善 NAFLD 的诊断和进展预测。在这篇综述中，我们旨在了解糖尿病如何影响肝脂肪变性的发展及其进展为晚期肝损伤。首先，我们强调了 NAFLD 和糖尿病在全球范围内共同发生的程度。其次，我们探讨了参与 NAFLD 和 2 型糖尿病发病机制的主要机制，并讨论了这些机制是否使 NAFLD 在更好地理解 NCD 和传染性疾病（如 COVID-19）的发病机制方面处于重要地位。第三，我们探讨了这种知识是否可用于未来对 NAFLD 的个体化治疗。最后，我们讨论了目前治疗 2 型糖尿病患者的策略及其在治疗从单纯脂肪变性到非酒精性脂肪性肝炎和肝纤维化的一系列肝脏疾病方面的有效性。
