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Diabetes, Obesity and Metabolism
The Impact of Insulin Resistance on Hepatic Fibrosis among United States Adults with Non-Alcoholic Fatty Liver Disease: NHANES 2017 to 2018
Ji Cheol Bae, Lauren A. Beste, Kristina M. Utzschneider
Endocrinol Metab. 2022;37(3):455-465.   Published online June 21, 2022
DOI: https://doi.org/10.3803/EnM.2022.1434
  • 4,200 View
  • 135 Download
  • 9 Web of Science
  • 11 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We aimed to investigate the association of hepatic steatosis with liver fibrosis and to assess the interactive effects of hepatic steatosis and insulin resistance on liver fibrosis in a nationally representative sample of United States adults.
Methods
We conducted a cross-sectional analysis using data from National Health and Nutrition Examination Survey 2017 to 2018, which for the first time included transient elastography to assess liver stiffness and hepatic steatosis. We evaluated the association between hepatic steatosis (using controlled attenuation parameter [CAP]) and clinically significant liver fibrosis (defined as liver stiffness ≥7.5 kPa) using logistic regression with an interaction term for hepatic steatosis and insulin resistance (defined as homeostatic model assessment of insulin resistance ≥3.0).
Results
Among adults undergoing transient elastography (n=2,023), 45.9% had moderate or greater hepatic steatosis and 11.3% had clinically significant liver fibrosis. After adjustment for demographic and metabolic factors, the odds of significant liver fibrosis increased as CAP score rose (odds ratio, 1.35 per standard deviation increment; 95% confidence interval, 1.11 to 1.64). We detected a significant interaction effect between CAP score and insulin resistance on the probability of significant liver fibrosis (P=0.016 for interaction). The probability of significant liver fibrosis increased in the presence of insulin resistance with increasing CAP score, while those without insulin resistance had low probability of significant liver fibrosis, even with high CAP scores.
Conclusion
Individuals with hepatic steatosis had higher odds of fibrosis when insulin resistance was present. Our findings emphasize the importance of the metabolic aspects of the disease on fibrosis risk and suggest a need to better identify patients with metabolic associated fatty liver disease.

Citations

Citations to this article as recorded by  
  • Association of insulin resistance indicators with hepatic steatosis and fibrosis in patients with metabolic syndrome
    Tzu-chia Kuo, Yang-bor Lu, Chieh-lun Yang, Bin Wang, Lin-xin Chen, Ching-ping Su
    BMC Gastroenterology.2024;[Epub]     CrossRef
  • No More NAFLD: The Term Is Now MASLD
    Ji Cheol Bae
    Endocrinology and Metabolism.2024; 39(1): 92.     CrossRef
  • Insulin Resistance/Sensitivity Measures as Screening Indicators of Metabolic-Associated Fatty Liver Disease and Liver Fibrosis
    Mohammad E. Khamseh, Mojtaba Malek, Soodeh Jahangiri, Sohrab Nobarani, Azita Hekmatdoost, Marieh Salavatizadeh, Samira Soltanieh, Haleh Chehrehgosha, Hoda Taheri, Zeinab Montazeri, Fereshteh Attaran, Faramarz Ismail-Beigi, Fariba Alaei-Shahmiri
    Digestive Diseases and Sciences.2024;[Epub]     CrossRef
  • The association of Neuromedin U levels and non-alcoholic fatty liver disease: A comparative analysis
    Murat Keskin, Sercan Avul, Aylin Beyaz, Nizameddin Koca
    Heliyon.2024; 10(5): e27291.     CrossRef
  • Oral Insulin Alleviates Liver Fibrosis and Reduces Liver Steatosis in Patients With Metabolic Dysfunction-associated Steatohepatitis and Type 2 Diabetes: Results of Phase II Randomized, Placebo-controlled Feasibility Clinical Trial
    Yuval Ishay, Joel Neutel, Yotam Kolben, Ram Gelman, Orly Sneh Arbib, Oliver Lopez, Helena Katchman, Rizwana Mohseni, Miriam Kidron, Yaron Ilan
    Gastro Hep Advances.2024; 3(3): 417.     CrossRef
  • Comparative and Predictive Significance of Serum Leptin Levels in Non-alcoholic Fatty Liver Disease
    Mehwish Qamar, Abeer Fatima, Ambreen Tauseef, Muhammad I Yousufzai, Ibrahim Liaqat, Qanbar Naqvi
    Cureus.2024;[Epub]     CrossRef
  • Greater Severity of Steatosis Is Associated with a Higher Risk of Incident Diabetes: A Retrospective Longitudinal Study
    Ji Min Han, Jung Hwan Cho, Hye In Kim, Sunghwan Suh, Yu-Ji Lee, Jung Won Lee, Kwang Min Kim, Ji Cheol Bae
    Endocrinology and Metabolism.2023; 38(4): 418.     CrossRef
  • Hepatic T-cell senescence and exhaustion are implicated in the progression of fatty liver disease in patients with type 2 diabetes and mouse model with nonalcoholic steatohepatitis
    Byeong Chang Sim, Yea Eun Kang, Sun Kyoung You, Seong Eun Lee, Ha Thi Nga, Ho Yeop Lee, Thi Linh Nguyen, Ji Sun Moon, Jingwen Tian, Hyo Ju Jang, Jeong Eun Lee, Hyon-Seung Yi
    Cell Death & Disease.2023;[Epub]     CrossRef
  • Familial clustering of nonalcoholic fatty liver disease in first‐degree relatives of adults with lean nonalcoholic fatty liver disease
    Sorachat Niltwat, Chanin Limwongse, Natthinee Charatcharoenwitthaya, Duangkamon Bunditvorapoom, Wimolrak Bandidniyamanon, Phunchai Charatcharoenwitthaya
    Liver International.2023; 43(12): 2713.     CrossRef
  • Metabolic Score for Insulin Resistance Is Inversely Related to Incident Advanced Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease
    Jun-Hyuk Lee, Yu-Jin Kwon, Kyongmin Park, Hye Sun Lee, Hoon-Ki Park, Jee Hye Han, Sang Bong Ahn
    Nutrients.2022; 14(15): 3039.     CrossRef
  • DPP-4 Inhibitor in Type 2 Diabetes Mellitus Patient with Non-Alcoholic Fatty Liver Disease: Achieving Two Goals at Once?
    Ji Cheol Bae
    Endocrinology and Metabolism.2022; 37(6): 858.     CrossRef
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Clinical Study
Development of a Non-Invasive Liver Fibrosis Score Based on Transient Elastography for Risk Stratification in Patients with Type 2 Diabetes
Chi-Ho Lee, Wai-Kay Seto, Kelly Ieong, David T.W. Lui, Carol H.Y. Fong, Helen Y. Wan, Wing-Sun Chow, Yu-Cho Woo, Man-Fung Yuen, Karen S.L. Lam
Endocrinol Metab. 2021;36(1):134-145.   Published online February 24, 2021
DOI: https://doi.org/10.3803/EnM.2020.887
  • 4,498 View
  • 132 Download
  • 6 Web of Science
  • 6 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
In non-alcoholic fatty liver disease (NAFLD), transient elastography (TE) is an accurate non-invasive method to identify patients at risk of advanced fibrosis (AF). We developed a diabetes-specific, non-invasive liver fibrosis score based on TE to facilitate AF risk stratification, especially for use in diabetes clinics where TE is not readily available.
Methods
Seven hundred sixty-six adults with type 2 diabetes and NAFLD were recruited and randomly divided into a training set (n=534) for the development of diabetes fibrosis score (DFS), and a testing set (n=232) for internal validation. DFS identified patients with AF on TE, defined as liver stiffness (LS) ≥9.6 kPa, based on a clinical model comprising significant determinants of LS with the lowest Akaike information criteria. The performance of DFS was compared with conventional liver fibrosis scores (NFS, FIB-4, and APRI), using area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive and negative predictive values (NPV).
Results
DFS comprised body mass index, platelet, aspartate aminotransferase, high-density lipoprotein cholesterol, and albuminuria, five routine measurements in standard diabetes care. Derived low and high DFS cut-offs were 0.1 and 0.3, with 90% sensitivity and 90% specificity, respectively. Both cut-offs provided better NPVs of >90% than conventional fibrosis scores. The AUROC of DFS for AF on TE was also higher (P<0.01) than the conventional fibrosis scores, being 0.85 and 0.81 in the training and testing sets, respectively.
Conclusion
Compared to conventional fibrosis scores, DFS, with a high NPV, more accurately identified diabetes patients at-risk of AF, who need further evaluation by hepatologists.

Citations

Citations to this article as recorded by  
  • Implementation of a liver health check in people with type 2 diabetes
    Kushala W M Abeysekera, Luca Valenti, Zobair Younossi, John F Dillon, Alina M Allen, Mazen Noureddin, Mary E Rinella, Frank Tacke, Sven Francque, Pere Ginès, Maja Thiele, Philip N Newsome, Indra Neil Guha, Mohammed Eslam, Jörn M Schattenberg, Saleh A Alqa
    The Lancet Gastroenterology & Hepatology.2024; 9(1): 83.     CrossRef
  • Sequential algorithm to stratify liver fibrosis risk in overweight/obese metabolic dysfunction-associated fatty liver disease
    Chi-Ho Lee, David Tak-Wai Lui, Raymond Hang-Wun Li, Michele Mae-Ann Yuen, Carol Ho-Yi Fong, Ambrose Pak-Wah Leung, Justin Chiu-Man Chu, Loey Lung-Yi Mak, Tai-Hing Lam, Jean Woo, Yu-Cho Woo, Aimin Xu, Hung-Fat Tse, Kathryn Choon-Beng Tan, Bernard Man-Yung
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Non-Invasive Measurement of Hepatic Fibrosis by Transient Elastography: A Narrative Review
    Luca Rinaldi, Chiara Giorgione, Andrea Mormone, Francesca Esposito, Michele Rinaldi, Massimiliano Berretta, Raffaele Marfella, Ciro Romano
    Viruses.2023; 15(8): 1730.     CrossRef
  • Metabolic dysfunction-associated fatty liver disease — How relevant is this to primary care physicians and diabetologists?
    Chi-Ho Lee
    Primary Care Diabetes.2022; 16(2): 245.     CrossRef
  • Non‐alcoholic fatty liver disease and type 2 diabetes: An update
    Chi‐H Lee, David TW Lui, Karen SL Lam
    Journal of Diabetes Investigation.2022; 13(6): 930.     CrossRef
  • Ultrasound-Based Hepatic Elastography in Non-Alcoholic Fatty Liver Disease: Focus on Patients with Type 2 Diabetes
    Georgiana-Diana Cazac, Cristina-Mihaela Lăcătușu, Cătălina Mihai, Elena-Daniela Grigorescu, Alina Onofriescu, Bogdan-Mircea Mihai
    Biomedicines.2022; 10(10): 2375.     CrossRef
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Namgok Lecture 2013
Obesity and Metabolism
Ectopic Fat Assessment Focusing on Cardiometabolic and Renal Risk
Soo Lim
Endocrinol Metab. 2014;29(1):1-4.   Published online March 14, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.1.1
  • 3,843 View
  • 59 Download
  • 36 Web of Science
  • 36 Crossref
AbstractAbstract PDFPubReader   

It is well known that people with high levels of body fat are at higher risk for developing diabetes mellitus, kidney disease, and cardiovascular disorders. Since individuals who are slightly overweight, or even individuals of normal weight, can vary in body fat distribution, their metabolic profiles and the degree of association of these profiles with cardiometabolic risk factors may differ. Fat distribution might be more of a predictive factor for cardiorenometabolic risk than obesity itself, which has led researchers to investigate whether ectopic fat accumulation may partially account for the development of cardiorenometabolic disorders. In addition to visceral obesity, fat can accumulate in the liver and muscle, and these intrahepatic and intramuscular lipid stores are associated with insulin resistance and adverse metabolic phenotypes. More recently, pericardial fat, perivascular fat, and perirenal fat were found to be associated with coronary atherosclerosis, cardiovascular diseases, and kidney damage, respectively. Thus, regional fat distribution may play a key role in understanding the development of cardiorenometabolic diseases in nonobese people.

Citations

Citations to this article as recorded by  
  • Renal stiffness measured by shear wave elastography and its relationship with perirenal fat in patients with chronic kidney disease
    Yiming Li, Yongzhan Liu, Lili Gao, Chuan Tian
    Journal of Clinical Ultrasound.2024; 52(1): 3.     CrossRef
  • Characterization of Green and Yellow Papaya (Carica papaya) for Anti-Diabetic Activity in Liver and Myoblast Cells and Wound-Healing Activity in Fibroblast Cells
    Haiwen Li, Obaid Ullah Beg, Ahmed Reza Rafie, Sadia Kanwal, Alexandra Ovalle-Cisneros, Milton Omar Faison, Rafat Ali Siddiqui
    Nutrients.2023; 15(8): 1929.     CrossRef
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    Goh Eun Chung, Kyungdo Han, Kyu-Na Lee, Jung Ho Bae, Sun Young Yang, Su-Yeon Choi, Jeong Yoon Yim, Nam Ju Heo
    Diabetes & Metabolism.2023; 49(4): 101454.     CrossRef
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    Clinical Genitourinary Cancer.2022; 20(1): e75.     CrossRef
  • The Influence of Obesity and Metabolic Health on Vascular Health
    Eun-Jung Rhee
    Endocrinology and Metabolism.2022; 37(1): 1.     CrossRef
  • Obesity‐related glomerulopathy: Current approaches and future perspectives
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    Diabetes Research and Clinical Practice.2014; 106(3): 590.     CrossRef
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