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

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

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

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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Crossref · 10.1016/j.jhepr.2019.07.002

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  • The weight gain with Pioglitazone could be part of its therapeutic action (lipid partitioning with expansion of subcutaneous adipose tissue).

    “which however could be part of the therapeutic action (lipid partitioning with the expansion of subcutaneous adipose tissue) [36].”

    From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [36]

    The “Metformin and pioglitazone” section says pioglitazone redistributes triglycerides from the liver and other tissues to metabolically healthier adipose tissue, explaining the weight gain. It also links weight gain to improved insulin action and reduced visceral fat. The section does not specify expansion of subcutaneous adipose tissue, so that detail is not supported by our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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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
Venue
JHEP Reports
Publisher
Elsevier BV
Published
2019-10
Volume
1
Issue
4
Pages
312-328
ISSN
2589-5559 (ISSN-L)
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 · 2018: 1 · 2017: 1
FWCI
6.46
Type
journal article
Language
en
Open access
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 › Epidemiology › 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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