Nonalcoholic Fatty Liver Disease and Type 2 Diabetes: Common Pathophysiologic Mechanisms

  • Chiara Saponaro
  • Melania Gaggini
  • Amalia Gastaldelli
Diabetes, Other Diseases, and New Complications: Emerging Associations (JJ Nolan, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Diabetes, Other Diseases, and New Complications: Emerging Associations


Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for advanced liver disease, type 2 diabetes (T2DM), and cardiovascular diseases. The prevalence of NAFLD in the general population is around 30 %, but it is up to three times higher in those with T2DM. Among people with obesity and T2DM, the NAFLD epidemic also is worsening. Therefore, it is important to identify early metabolic alterations and to prevent these diseases and their progression. In this review, we analyze the pathophysiologic mechanisms leading to NAFLD, particularly, those common to T2DM, such as liver and muscle insulin resistance. However, it is mainly adipose tissue insulin resistance that results in increased hepatic de novo lipogenesis, inflammation, and lipotoxicity. Although genetics predispose to NAFLD, an unhealthy lifestyle, including high-fat/high-sugar diets and low physical activity, increases the risk. In addition, alterations in gut microbiota and environmental chemical agents, acting as endocrine disruptors, may play a role.


Fatty liver Glucose intolerance De novo lipogenesis Lipotoxicity Gut microbiota Endocrine disruptors NASH 



This work was supported by institutional grants of the CNR.

Compliance with Ethics Guidelines

Conflict of Interest

Chiara Saponaro is recipient of a research scholarship awarded by “Dottorato Pegaso Regione Toscana in Biochimica e Biologia Molecolare” she has no conflict of interest.

Melania Gaggini is recipient of a research fellowship awarded by Gilead.

Amalia Gastaldelli reports personal fees from Roche and Eli Lilly, and grants from Amylin-BMS-AstraZeneca.

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.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Chiara Saponaro
    • 1
    • 2
  • Melania Gaggini
    • 1
    • 3
  • Amalia Gastaldelli
    • 1
  1. 1.Cardiometabolic Risk UnitInstitute of Clinical Physiology, CNRPisaItaly
  2. 2.Dipartimento di Biotecnologie, Chimica e FarmaciaUniversità di SienaSienaItaly
  3. 3.Dipartimento di Patologia Chirurgica, Molecolare Medica e di Area CriticaUniversità di PisaPisaItaly

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