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R E V I E W S
Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Medical University Innsbruck, Anichstrasse 35, 6020Innsbruck, Austria.
Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University.
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, c/oAufm Hennekamp 65, 40225 Dsseldorf, Germany.
German Center of Diabetes Research, Ingolstdter Landstrae 1, 85764, Mnchen-Neuherberg, Germany.
Correspondence to H.T. and M.R. mailto:[email protected]
Web End [email protected] ; mailto:[email protected]
Web End =michael.roden@ mailto:[email protected]
Web End =ddz.uni-duesseldorf.de
http://dx.doi.org/10.1038/nrgastro.2016.147
Web End =doi:10.1038/nrgastro.2016.147 Published online 12 Oct 2016
One of the most common liver disorders worldwide1,
NAFLD covers a disease spectrum, ranging from simple steatosis in the absence of inflammation to NASH, liver cirrhosis and hepatocellular carcinoma (HCC)2,3.
The number of patients in the general population with NAFLD who have NASH is unclear, but exceeds >10% of the overall NAFLD population, and population prevalence might be as high as 5%4. Definitive diagnosis of NASH is important as inflammation and/or fibrosis dictate the longterm prognosis of this disease5. In particular, NASH is predicted to become the leading cause of liver transplantation in many countries in the coming years6.
Although no established treatment for NASH currently exists, several therapeutic approaches such as the use of peroxisome proliferatoractivated receptor (PPAR) agonists, vitaminE or liraglutide have demonstrated some clinical efficacy in the past few years7,8.
Insulin resistance has been characterized as the crucial pathophysiological factor in NAFLD9. However, the mechanistic basis of NAFLD and NASH is still incompletely understood, and besides insulin resistance perse, lipids, mitochondrial function, innate immunity, intestinal microbiota, genetic determinants, nutritional factors and lifestyle are involved in the disease process10,11. Astrong association between NAFLD and type2 diabetes mellitus (T2DM) has been shown, as >70% of patients with T2DM have NAFLD12,13. The
burden of NAFLD, with clinically relevant fibrosis affecting up to 20% of those with both NAFLD and T2DM, seems to be enormous1416 considering the huge number of patients with T2DM worldwide17. Thus, not only is NAFLD highly associated with insulin resistance,
butT2DM is commonly accompanied by NAFLD, with a very high rate of NASH1820. This Review will highlight pathophysio logical and clinical aspects of the association between NAFLD andT2DM.
Pathophysiological aspects Hepatic lipids and energy metabolism
All forms of NAFLD tightly correlate...