Azienda Ospedaliero-Universitaria Modena, UO di Medicina Metabolica, Ospedale Civile di Baggiovara, Via Giardini 1135, 41125, Modena, Italy.
Università di Modena e Reggio Emilia, via del Pozzo, 71, 41124, Modena, Italy.
Acta Diabetol. 2019 Apr;56(4):385-396. doi: 10.1007/s00592-018-1266-0. Epub 2018 Dec 5.
Evidence suggests a close relationship between nonalcoholic fatty liver disease (NAFLD) and type two diabetes (T2D). On the grounds of prevalence of disease, both conditions account for a significant financial cost for health care systems and individuals. Aim of this review article is to explore the epidemiological basis and the putative molecular mechanisms underlying the association of NAFLD with T2D. Epidemiological studies have shown that NAFLD is associated to the development of incident T2D and either reversal or improvement of NAFLD will result into decreased risk of developing incident T2D. On the other side of the coin data have shown that T2D will worsen the course of NAFLD doubling the risk of disease progression (i.e. evolution from simple steatosis to advanced fibrosis, cirrhosis, hepatocellular carcinoma, liver transplant and death). Conversely, NAFLD will contribute to metabolic decompensation of T2D. The pathogenesis of T2D in NAFLD patients may be mediated by several hepatokines impairing metabolic control. Among these, Fetuin-B, which causes glucose intolerance and is increased in patients with T2D and NAFLD with fibrosis is one of the most promising. T2D may affect the progression of NAFLD by acting at different levels of the pathogenic cascade involving gut microbiota and expanded, inflamed, dysfunctional adipose tissue. In conclusion, T2D and NAFLD are mutually, closely and bi-directionally associated. An improved understanding of molecular pathogenesis underlying this bi-directional association may allow us to be able to prevent the development of T2D by halting the progression of NAFLD.
有证据表明，非酒精性脂肪性肝病（NAFLD）与 2 型糖尿病（T2D）之间存在密切关系。就疾病的流行程度而言，这两种疾病都会给医疗保健系统和个人带来巨大的经济负担。本文旨在探讨 NAFLD 与 T2D 相关的流行病学基础和潜在的分子机制。流行病学研究表明，NAFLD 与 2 型糖尿病的发生有关，NAFLD 的逆转或改善将降低发生 2 型糖尿病的风险。另一方面，数据表明，T2D 会使 NAFLD 的病程恶化，使疾病进展的风险增加一倍（即从单纯脂肪变性发展为进展性纤维化、肝硬化、肝细胞癌、肝移植和死亡）。相反，NAFLD 会导致 T2D 的代谢失代偿。NAFLD 患者的 T2D 发病机制可能是由几种肝细胞因子介导的，这些因子会损害代谢控制。其中，Fetuin-B 是一种导致葡萄糖不耐受的因子，在 T2D 和伴有纤维化的 NAFLD 患者中增加，是最有前途的因子之一。T2D 可能通过作用于涉及肠道微生物群和扩张、炎症、功能失调的脂肪组织的致病级联反应的不同水平来影响 NAFLD 的进展。总之，T2D 和 NAFLD 是相互关联的，而且是双向的。对这种双向关联的分子发病机制的深入了解，可能使我们能够通过阻止 NAFLD 的进展来预防 T2D 的发生。
