Review
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Sep 27, 2020; 12(9): 533-557
Published online Sep 27, 2020. doi: 10.4254/wjh.v12.i9.533
Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases
Waihong Chung, Kittichai Promrat, Jack Wands
Waihong Chung, Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, Providence, RI 02905, United States
Kittichai Promrat, Division of Gastroenterology and Hepatology, Providence VA Medical Center, Providence, RI 02908, United States
Jack Wands, Liver Research Center, The Warren Alpert Medical School of Brown University, Providence, RI 02903, United States
Author contributions: Chung W conducted the literature review and wrote the manuscript; Promrat K reviewed and revised the manuscript; Wands J reviewed the manuscript and supervised the project; all authors have read and approved the final manuscript.
Conflict-of-interest statement: The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Waihong Chung, MD, PhD, Doctor, Research Fellow, Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, 245 Chapman Street, Suite 300, Providence, RI 02905, United States. waihongchung@gmail.com
Received: July 8, 2020
Peer-review started: July 8, 2020
First decision: July 30, 2020
Revised: August 3, 2020
Accepted: August 15, 2020
Article in press: August 15, 2020
Published online: September 27, 2020
Processing time: 75 Days and 13.4 Hours
Abstract

Diabetes mellitus (DM) negatively affects the development and progression of chronic liver diseases (CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma (HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.

Keywords: End stage liver disease; Diabetes mellitus; Liver cirrhosis; Insulin resistance; Non-alcoholic fatty liver disease; Liver diseases

Core Tip: Diabetes is an independent risk factor for the development and progression of chronic liver disease (CLD) of various etiologies. Concurrent diabetes and CLD predict worse clinical outcomes, including hepatic decompensation, hepatocellular carcinoma (HCC), and complications following liver transplantation. Traditional glycemic markers, including fasting glucose, oral glucose tolerance test, and hemoglobin A1c, are not accurate in patients with severe CLD. Metformin and α-glucosidase inhibitors are associated with significant benefits beyond glycemic control, including reductions in HCC risk and incidence of hepatic encephalopathy. Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors may exert a hepatic protective effect irrespective of the degree of glycemic control.