Cited by 456Liver Disease Diagnosis and TreatmentDiabetes, Cardiovascular Risks, and LipoproteinsDiet, Metabolism, and Disease

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From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options

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Gastaldelli, Amalia, Cusi, Kenneth·2019·JHEP Reports

DOI 10.1016/j.jhepr.2019.07.002PMC PMC7001557

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Abstract

The worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to have reached 25% or more in adults. NAFLD is prevalent in obese individuals, but may also affect non-obese insulin-resistant individuals. NAFLD is associated with a 2- to 3-fold increased risk of developing type 2 diabetes (T2D), which may be higher in patients with more severe liver disease - fibrosis increases this risk. In NAFLD, not only the close association with obesity, but also the impairment of many metabolic pathways, including decreased hepatic insulin sensitivity and insulin secretion, increase the risk of developing T2D and related comorbidities. Conversely, patients with diabetes have a higher prevalence of steatohepatitis, liver fibrosis and end-stage liver disease. Genetics and mechanisms involving dysfunctional adipose tissue, lipotoxicity and glucotoxicity appear to play a role. In this review, we discuss the altered pathophysiological mechanisms that underlie the development of T2D in NAFLD and vice versa. Although there is no approved therapy for the treatment of NASH, we discuss pharmacological agents currently available to treat T2D that could potentially be useful for the management of NASH.

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Authors: Gastaldelli, A., & Cusi, K.
Affiliations: Istituto di Fisiologia Clinica (IT)
University of Florida (US)
Corresponding author: Gastaldelli, Amalia
Cusi, Kenneth
ORCID: Gastaldelli, Amalia
Cusi, Kenneth
Venue: JHEP Reports
Publisher: Elsevier BV
Published: 2019-10
Volume: 1
Issue: 4
Pages: 312-328
ISSN: 2589-5559 (ISSN-L)
DOI: 10.1016/j.jhepr.2019.07.002
PMC: PMC7001557
OpenAlex: W2963543751
Cited by: 455
References: 231
Citations by year: 2026: 48 · 2025: 69 · 2024: 85 · 2023: 74 · 2022: 62 · 2021: 78 · 2020: 34 · 2019: 3
FWCI: 6.46
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: JHEP Reports (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Horizon H2020 (634413)
Topics: Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords: non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, type 2 diabetes, insulin resistance, hepatic insulin sensitivity, insulin secretion, liver fibrosis, end-stage liver disease, lipotoxicity, glucotoxicity, adipose tissue dysfunction, obesity, antidiabetic drugs

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