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Why Does NAFLD Predict Type 2 Diabetes?

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Abstract

Based on the “lipotoxic” hypothesis, the free fatty acid flux from the excessive amount of adipose tissue toward the peripheral tissues would induce the development of insulin resistance especially when the triglyceride storage or the concentration of intermediate fat metabolites (diacylglycerides, ceramides) within the cytoplasm of these cells become excessive. Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis and advanced fibrosis. NAFLD is associated with general and intra-abdominal obesity and with a reduced ability of insulin to stimulate metabolic pathways in the liver itself and in other tissues. There are animal models and models in human diseases sustaining the hypothesis that a primary hepatic disease may determine the development of type 2 diabetes (T2DM). Epidemiologic data generated on surrogate markers of NAFLD (transaminases and γ-glutamyltransferase), semiquantitative assessment of fatty liver (ultrasound), and surrogate algorithms of NAFLD also support a causative effect of NAFLD on the risk to develop T2DM. In spite of the presence of these indirect associations, a clear-cut link between NAFLD and abnormal β-cell function is yet to be reported. Therefore, more data are warranted to prove what is considered a likely causative relationship between NAFLD and T2DM.

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Acknowledgments

The writing of this paper was supported by a liberal donation by the Angela Musazzi and Mario Stellato family and by a grant from European Federation for the Study of Diabetes (EFSD).

Disclosure

Conflicts of interest: G. Lattuada: none; F. Ragogna: none; G. Perseghin: has been a consultant for Takeda; has received honoraria from Takeda, GlaxoSmithKline, Sanofi-Aventis, Guidotti, MSD, Eli Lilly, Novartis, and Schering-Plough; has received travel expenses from AstraZeneca; and has received grant support from Novo Nordisk, Guidotti, and Novartis.

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Authors and Affiliations

  1. Department of Sport, Nutrition and Health, Università degli Studi di Milano, via Kramer 4/A, 20129, Milan, Italy

    Guido Lattuada & Gianluca Perseghin

  2. Division of Metabolic and Cardiovascular Sciences, Istituto Scientifico H San Raffaele, via Olgettina 60, 20132, Milan, Italy

    Guido Lattuada, Francesca Ragogna & Gianluca Perseghin

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  1. Guido Lattuada
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  2. Francesca Ragogna
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  3. Gianluca Perseghin
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Correspondence to Gianluca Perseghin.

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Lattuada, G., Ragogna, F. & Perseghin, G. Why Does NAFLD Predict Type 2 Diabetes?. Curr Diab Rep 11, 167–172 (2011). https://doi.org/10.1007/s11892-011-0190-2

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