Diabetes Metab J.  2024 May;48(3):327-339. 10.4093/dmj.2023.0350.

Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective

• Jung I
• Koo DJ
• Lee WY

• KMID: 2555765
• DOI: http://doi.org/10.4093/dmj.2023.0350

Abstract

It has been generally accepted that insulin resistance (IR) and reduced insulin secretory capacity are the basic pathogenesis of type 2 diabetes mellitus (T2DM). In addition to genetic factors, the persistence of systemic inflammation caused by obesity and the associated threat of lipotoxicity increase the risk of T2DM. In particular, the main cause of IR is obesity and subjects with T2DM have a higher body mass index (BMI) than normal subjects according to recent studies. The prevalence of T2DM with IR has increased with increasing BMI during the past three decades. According to recent studies, homeostatic model assessment of IR was increased compared to that of the 1990s. Rising prevalence of obesity in Korea have contributed to the development of IR, non-alcoholic fatty liver disease and T2DM and cutting this vicious cycle is important. My colleagues and I have investigated this pathogenic mechanism on this theme through clinical and experimental studies over 20 years and herein, I would like to summarize some of our studies with deep gratitude for receiving the prestigious 2023 Sulwon Award.

Keyword

Diabetes mellitus, type 2; Insulin resistance; Non-alcoholic fatty liver disease; Obesity

Figure

• 

  Fig. 1. Schematic representation of the pathophysiology in insulin resistance associated with metabolic disorders and progression to non-alcoholic fatty liver disease and type 2 diabetes mellitus (T2DM). TNF-α, tumor necrosis factor-α; IL-6, interleukin-6; hsCRP, high-sensitivity C-reactive protein; IFN-γ, interferon-γ; FA, fatty acids; ER, endoplasmic reticulum; ROS, reactive oxygen species; PPAR, peroxisome proliferator-activated receptor; GLP-1RA, glucagon-like peptide-1 receptor agonist; DPP-4, dipeptidyl peptidase-4; SGLT-2, sodium-glucose cotransporter-2; Ex-4, exendin-4; FXR, farnesoid X receptor; CVD, cardiovascular disease; HCC, hepatocellular carcinoma. aAbsolutely, bProbably, cPossibly.

• 

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