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Review
. 2023 Jun 2;24(11):9677.
doi: 10.3390/ijms24119677.

Type 2 Diabetes Mellitus, Non-Alcoholic Fatty Liver Disease, and Metabolic Repercussions: The Vicious Cycle and Its Interplay with Inflammation

Rafał Frankowski  1 , Mateusz Kobierecki  1 , Andrzej Wittczak  1 , Monika Różycka-Kosmalska  2 , Tadeusz Pietras  3 , Kasper Sipowicz  4 , Marcin Kosmalski  3
Affiliations
Review

Type 2 Diabetes Mellitus, Non-Alcoholic Fatty Liver Disease, and Metabolic Repercussions: The Vicious Cycle and Its Interplay with Inflammation

Rafał Frankowski et al. Int J Mol Sci. .

Abstract

The prevalence of metabolic-related disorders, such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (DM2), has been increasing. Therefore, developing improved methods for the prevention, treatment, and detection of these two conditions is also necessary. In this study, our primary focus was on examining the role of chronic inflammation as a potential link in the pathogenesis of these diseases and their interconnections. A comprehensive search of the PubMed database using keywords such as "non-alcoholic fatty liver disease", "type 2 diabetes mellitus", "chronic inflammation", "pathogenesis", and "progression" yielded 177 relevant papers for our analysis. The findings of our study revealed intricate relationships between the pathogenesis of NAFLD and DM2, emphasizing the crucial role of inflammatory processes. These connections involve various molecular functions, including altered signaling pathways, patterns of gene methylation, the expression of related peptides, and up- and downregulation of several genes. Our study is a foundational platform for future research into the intricate relationship between NAFLD and DM2, allowing for a better understanding of the underlying mechanisms and the potential for introducing new treatment standards.

Keywords: chronic inflammation; cytokines; non-alcoholic fatty liver disease; oxidative stress; pathogenesis; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The pathogenesis of NAFLD and NASH in terms of inflammation. Abbreviations: CCL, chemokine (C–C motif) ligand; CCR, C–C chemokine receptors; CXCL1, chemokine (C–X–C motif) ligand 1; DM2, type 2 diabetes mellitus; HSF1, heat-shock transcription factor-1; HSP70, 70 kDa family of heat-shock proteins; IL, interleukin; iNOS, inducible nitric oxide synthase; IP-10, IFN-γ-induced protein (IP-10); IR, insulin resistance; MMP, matrix metalloproteinase; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; PIIINP, procollagen-III peptide; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator 1α; TGF-β1, transforming growth factor beta 1; TNF-α, tumor necrosis factor α; ↑, increase; ↓, decrease.
Figure 2
Figure 2
The pathogenesis of DM2 in terms of inflammation. Abbreviations: DM2, type 2 diabetes mellitus; hs-CRP, high-sensitivity C-reactive protein; ICAM-1, intercellular adhesion molecule-1; IL, interleukin; IR, insulin resistance; NLPR3i, domain-like receptor protein 3 (NLRP3) inflammasome; TNF-α, tumor necrosis factor α; VCAM-1, vascular cell adhesion molecule-1.
Figure 3
Figure 3
The relationships between NAFLD, DM2, and inflammation. Abbreviations: DM2, type 2 diabetes mellitus; NAFLD, non-alcoholic fatty liver disease.
See this image and copyright information in PMC

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