PMID- 32569680
OWN - NLM
STAT- MEDLINE
DCOM- 20201102
LR  - 20210110
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 111S
DP  - 2020 Oct
TI  - Metabolic liver disease in diabetes - From mechanisms to clinical trials.
PG  - 154299
LID - S0026-0495(20)30163-3 [pii]
LID - 10.1016/j.metabol.2020.154299 [doi]
AB  - Non-alcoholic fatty liver disease (NAFLD) comprises fatty liver (steatosis), 
      non-alcoholic steatohepatitis (NASH) and fibrosis/cirrhosis and may lead to 
      end-stage liver failure or hepatocellular carcinoma. NAFLD is tightly associated 
      with the most frequent metabolic disorders, such as obesity, metabolic syndrome, 
      and type 2 diabetes mellitus (T2DM). Both multisystem diseases share several 
      common mechanisms. Alterations of tissue communications include excessive lipid 
      and later cytokine release by dysfunctional adipose tissue, intestinal dysbiosis 
      and ectopic fat deposition in skeletal muscle. On the hepatocellular level, this 
      leads to insulin resistance due to abnormal lipid handling and mitochondrial 
      function. Over time, cellular oxidative stress and activation of inflammatory 
      pathways, again supported by multiorgan crosstalk, determine NAFLD progression. 
      Recent studies show that particularly the severe insulin resistant diabetes 
      (SIRD) subgroup (cluster) associates with NAFLD and its accelerated progression 
      and increases the risk of diabetes-related cardiovascular and kidney diseases, 
      underpinning the critical role of insulin resistance. Consequently, lifestyle 
      modification and certain drug classes used to treat T2DM have demonstrated 
      effectiveness for treating NAFLD, but also some novel therapeutic concepts may be 
      beneficial for both NAFLD and T2DM. This review addresses the bidirectional 
      relationship between mechanisms underlying T2DM and NAFLD, the relevance of novel 
      biomarkers for improving the diagnostic modalities and the identification of 
      subgroups at specific risk of disease progression. Also, the role of 
      metabolism-related drugs in NAFLD is discussed in light of the recent clinical 
      trials. Finally, this review highlights some challenges to be addressed by future 
      studies on NAFLD in the context of T2DM.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Dewidar, Bedair
AU  - Dewidar B
AD  - Institute of Clinical Diabetology, German Diabetes Center, Dusseldorf, Germany; 
      German Center for Diabetes Research, Munchen-Neuherberg, Germany; Department of 
      Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
FAU - Kahl, Sabine
AU  - Kahl S
AD  - Institute of Clinical Diabetology, German Diabetes Center, Dusseldorf, Germany; 
      German Center for Diabetes Research, Munchen-Neuherberg, Germany.
FAU - Pafili, Kalliopi
AU  - Pafili K
AD  - Institute of Clinical Diabetology, German Diabetes Center, Dusseldorf, Germany.
FAU - Roden, Michael
AU  - Roden M
AD  - Institute of Clinical Diabetology, German Diabetes Center, Dusseldorf, Germany; 
      German Center for Diabetes Research, Munchen-Neuherberg, Germany; Division of 
      Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, 
      Dusseldorf, Germany. Electronic address: michael.roden@ddz.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200620
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Biomarkers)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Diabetes Mellitus, Type 2/metabolism/*pathology
MH  - Disease Progression
MH  - Humans
MH  - Liver Cirrhosis/metabolism/pathology
MH  - Metabolic Syndrome/metabolism/*pathology
MH  - Non-alcoholic Fatty Liver Disease/metabolism/pathology
MH  - Risk
PMC - PMC7305712
OTO - NOTNLM
OT  - Biomarkers
OT  - Clinical trials
OT  - Fatty liver
OT  - Glucose-lowering drugs
OT  - Insulin resistance
OT  - Type 2 diabetes
COIS- Declaration of competing interest BD, SK and KP declare no conflicts of interest. 
      MR is on the scientific advisory boards of Allergan, Astra-Zeneca, Bristol-Myers 
      Squibb, Eli Lilly, Gilead Sciences, Inventiva, Intercept Pharma, Novartis, 
      NovoNordisk, Servier Laboratories, Target Pharmasolutions, and Terra Firma and 
      receives investigator-initiated support from Boehringer Ingelheim, 
      Nutricia/Danone and Sanofi-Aventis.
EDAT- 2020/06/23 06:00
MHDA- 2020/11/03 06:00
PMCR- 2020/06/20
CRDT- 2020/06/23 06:00
PHST- 2020/04/25 00:00 [received]
PHST- 2020/06/04 00:00 [revised]
PHST- 2020/06/18 00:00 [accepted]
PHST- 2020/06/23 06:00 [pubmed]
PHST- 2020/11/03 06:00 [medline]
PHST- 2020/06/23 06:00 [entrez]
PHST- 2020/06/20 00:00 [pmc-release]
AID - S0026-0495(20)30163-3 [pii]
AID - 154299 [pii]
AID - 10.1016/j.metabol.2020.154299 [doi]
PST - ppublish
SO  - Metabolism. 2020 Oct;111S:154299. doi: 10.1016/j.metabol.2020.154299. Epub 2020 
      Jun 20.