Nonalcoholic fatty liver disease: cause or consequence of type 2 diabetes?

被引:127
作者
Valenti, Luca [1 ,2 ]
Bugianesi, Elisabetta [3 ]
Pajvani, Utpal [4 ]
Targher, Giovanni [5 ,6 ]
机构
[1] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Internal Med & Metab Dis, Milan, Italy
[2] Univ Milan, Dept Pathophysiol & Transplantat, Via Francesco Sforza 35, I-20122 Milan, Italy
[3] Univ Turin, AOU Citta Salute & Sci, Dept Med Sci, Div Gastroenterol, Turin, Italy
[4] Columbia Univ, Div Endocrinol, New York, NY USA
[5] Univ Verona, Dept Med, Sect Endocrinol Diabet & Metab, Verona, Italy
[6] Azienda Osped Univ Integrata Verona, Verona, Italy
关键词
genetics; insulin resistance; nonalcoholic fatty liver disease; pathophysiology; type; 2; diabetes; HEPATIC GLUCOKINASE EXPRESSION; TRANSCRIPTION FACTOR FOXO1; INSULIN-RESISTANCE; GLUCOSE-PRODUCTION; CONFERS SUSCEPTIBILITY; CARDIOVASCULAR-DISEASE; LIPID-METABOLISM; GENE-EXPRESSION; UNITED-STATES; HEPATOCELLULAR-CARCINOMA;
D O I
10.1111/liv.13185
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Growing epidemiological evidence suggests that nonalcoholic fatty liver disease (NAFLD) is an early predictor of and determinant for the development of type 2 diabetes and other features of the metabolic syndrome. This finding may have important clinical implications for the diagnosis, prevention and treatment of type 2 diabetes and its chronic complications. However, given the complex and bi-directional relationships between NAFLD, insulin resistance and chronic hyperglycaemia, it is extremely difficult to distinguish whether NAFLD is a cause or a consequence of insulin resistance and type 2 diabetes. Indeed, at the molecular level, hepatic lipogenesis and hepatic glucose production depend on differentially regulated branches of the insulin signalling pathway. Furthermore, genetic studies suggest that excess hepatic fat is associated with progressive liver disease, but does not always increase the risk of incident type 2 diabetes. Here, we will briefly review the epidemiological, pathophysiological and molecular evidence linking NAFLD to the development of type 2 diabetes. We will also discuss some recent genetic and therapeutic advances that seem to challenge a causal role of NAFLD in the pathogenesis type 2 diabetes, and propose a working hypothesis to explain this apparent conundrum. In conclusion, progressive liver disease and type 2 diabetes are divergent though inter-related consequences of insulin resistance and the metabolic syndrome.
引用
收藏
页码:1563 / 1579
页数:17
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