Insulin resistance is the pivotal pathogenic component of many metabolic diseases, including type 2 diabetes mellitus, and is defined as a state of reduced responsiveness of insulin-targeting tissues to physiological levels of insulin. Although the underlying mechanism of insulin resistance is not fully understood, several credible theories have been proposed. In this review, we summarize the functions of insulin in glucose metabolism in typical metabolic tissues and describe the mechanisms proposed to underlie insulin resistance, that is, ectopic lipid accumulation in liver and skeletal muscle, endoplasmic reticulum stress, and inflammation. In addition, we suggest potential therapeutic strategies for addressing insulin resistance.
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Diabetes Metab J. 2021;45(5):739-752. Published online October 28, 2020
Background Several noninvasive tools are available for the assessment of nonalcoholic fatty liver disease (NAFLD) including clinical and blood biomarkers, transient elastography (TE), and magnetic resonance imaging (MRI) techniques, such as proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE). In the present study, we aimed to evaluate whether magnetic resonance (MR)-based examinations better discriminate the pathophysiologic features and fibrosis progression in NAFLD than other noninvasive methods.
Methods A total of 133 subjects (31 healthy volunteers and 102 patients with NAFLD) were subjected to clinical and noninvasive NAFLD evaluation, with additional liver biopsy in some patients (n=54).
Results MRI-PDFF correlated far better with hepatic fat measured by MR spectroscopy (r=0.978, P<0.001) than with the TE controlled attenuation parameter (CAP) (r=0.727, P<0.001). In addition, MRI-PDFF showed stronger correlations with various pathophysiologic parameters for cellular injury, glucose and lipid metabolism, and inflammation, than the TE-CAP. The MRI-PDFF and TE-CAP cutoff levels associated with abnormal elevation of serum alanine aminotransferase were 9.9% and 270 dB/m, respectively. The MRE liver stiffness measurement (LSM) showed stronger correlations with liver enzymes, platelets, complement component 3, several clinical fibrosis scores, and the enhanced liver fibrosis (ELF) score than the TE-LSM. In an analysis of only biopsied patients, MRE performed better in discriminating advanced fibrosis with a cutoff value of 3.9 kPa than the TE (cutoff 8.1 kPa) and ELF test (cutoff 9.2 kPa).
Conclusion Our results suggest that MRI-based assessment of NAFLD is the best non-invasive tool that captures the histologic, pathophysiologic and metabolic features of the disease.
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An individual patient data meta-analysis to determine cut-offs for and confounders of NAFLD-fibrosis staging with magnetic resonance elastography Jia-xu Liang, Javier Ampuero, Hao Niu, Kento Imajo, Mazen Noureddin, Jaideep Behari, Dae Ho Lee, Richard L. Ehman, Fredrik Rorsman, Johan Vessby, Juan R. Lacalle, Ferenc E. Mózes, Michael Pavlides, Quentin M. Anstee, Stephen A. Harrison, Javier Castell, R Journal of Hepatology.2023; 79(3): 592. CrossRef
Relationship between controlled attenuated parameter and magnetic resonance imaging–proton density fat fraction for evaluating hepatic steatosis in patients with NAFLD Ziming An, Qiaohong Liu, Wenli Zeng, Yan Wang, Qian Zhang, Huafu Pei, Xin Xin, Shuohui Yang, Fang Lu, Yu Zhao, Yiyang Hu, Qin Feng Hepatology Communications.2022; 6(8): 1975. CrossRef
Noninvasive imaging of hepatic dysfunction: A state-of-the-art review Ting Duan, Han-Yu Jiang, Wen-Wu Ling, Bin Song World Journal of Gastroenterology.2022; 28(16): 1625. CrossRef
Diagnosis and Pathogenesis of Sarcopenia in Chronic Liver Disease Using Liver Magnetic Resonance Imaging Atsushi Nakamura, Tsubasa Yoshimura, Tomomi Sato, Takeshi Ichikawa Cureus.2022;[Epub] CrossRef
Plasma Aldo-Keto Reductase Family 1 Member B10 as a Biomarker Performs Well in the Diagnosis of Nonalcoholic Steatohepatitis and Fibrosis Aron Park, Seung Joon Choi, Sungjin Park, Seong Min Kim, Hye Eun Lee, Minjae Joo, Kyoung Kon Kim, Doojin Kim, Dong Hae Chung, Jae Been Im, Jaehun Jung, Seung Kak Shin, Byung-Chul Oh, Cheolsoo Choi, Seungyoon Nam, Dae Ho Lee International Journal of Molecular Sciences.2022; 23(9): 5035. CrossRef
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Plasma Metabolomics and Machine Learning-Driven Novel Diagnostic Signature for Non-Alcoholic Steatohepatitis Moongi Ji, Yunju Jo, Seung Joon Choi, Seong Min Kim, Kyoung Kon Kim, Byung-Chul Oh, Dongryeol Ryu, Man-Jeong Paik, Dae Ho Lee Biomedicines.2022; 10(7): 1669. CrossRef
Updated S2k Clinical Practice Guideline on Non-alcoholic Fatty Liver Disease (NAFLD) issued by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) – April 2022 – AWMF Registration No.: 021–025
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Jong Hyung Choi, Doo Man Kim, Han Su Cho, Ki Sung Lee, Ji Young Seo, Hyun Kyoo Kim, Cheol Soo Choi, Sung Hee Ihm, Jae Myung Yu, Moon Ki Choi, Hyung Joon Yoo, Sung Woo Park
Korean Diabetes J. 2000;24(5):614-618. Published online January 1, 2001
The serum amylase level is widely used as a screening test for acute pancreatitis and rises also in a wide variety of diseases involving the pancreas, salivary glands, intestines, liver, genitourinary tract, and lung, in metabolic aberrations such as diabetic ketoacidosis, and even during normal pregnancy. Although it is commonly assumed that the diseased organ is releasing amylase into the serum, in many conditions the precise relationship between the hyperamylasemia and the condition is not clear. Serum amylase is abnormally elevated in more than 60% of patients with diabetic ketoacidosis, but increased pancreatic enzyme activity, even in combination with abdominal pain, should not be diagnosed as acute pancreatitis. In nonketotic hyperosmolar syndrome, elevated serum amylase level without pancreatitis has not been reported. Nonketotic hyperosmolar syndrome is usually a complcation of type 2 DM and characterized by severe hyperosmolarity (serum osmolality> or =320 mOsm/L), hyperglycemia (serum glucose> or = 600 mg/dL) and dehydration. We experienced two cases of nonketotic hyperosmolar syndrome with elevated serum amylase. Serum amylase level was 1556 U/L in first case, 229 U/L in second case. Two patients did not complain of abdominal pain, nausea, vomiting and abdomen CT with enhancement showed the normal pancreases.