Role of Insulin Resistance and Diabetes in the Pathogenesis and Treatment of Nonalcoholic Fatty Liver Disease
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Nonalcoholic fatty liver disease (NAFLD) is now a frequent cause of consultation for hepatologists and other health care providers. To a significant extent, this is because the metabolic abnormalities associated with obesity and type 2 diabetes mellitus (T2DM) promote liver disease and are more prevalent than ever before. Clinicians must be aware that insulin resistance and hyperglycemia are believed to worsen the natural history of NAFLD, fueling inflammation, hepatocyte injury (ballooning) and fibrosis. End-stage liver disease and hepatocellular carcinoma (HCC) develop more often in this setting. Interventions that reverse insulin resistance and hyperglycemia, may halt or ameliorate the disease process. Therefore, a comprehensive approach is needed for the successful management of these patients that addresses both, the liver-specific and the associated metabolic conditions. This review focuses on the mechanisms by which insulin resistance, and both lipo- and glucotoxicity, are believed to contribute to the development of NAFLD, and on the treatments tested in obese patients with T2DM and NAFLD, as a means to assist practitioners managing these complex patients.
KeywordsFatty liver Nonalcoholic fatty liver disease (NAFLD) Steatosis Nonalcoholic steatohepatitis (NASH) Treatment Type 2 diabetes mellitus Obesity Insulin resistance Hyperglycemia Lipotoxicity Glucotoxicity Pioglitazone, Vitamin E Obeticholic acid Metformin Exenatide Liraglutide
This work was supported by the American Diabetes Association (to K. C.) and a VA Merit Award (1 I01 CX000167-01; to K. C.).
Compliance with Ethics Guidelines
Conflict of Interest
Paola Portillo-Sanchez, Sahzene Yavuz, Fernando Bril and Kenneth Cusi declare no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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