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Metabolic Risk/Epidemiology
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A Composite Blood Biomarker Including AKR1B10 and Cytokeratin 18 for Progressive Types of Nonalcoholic Fatty Liver Disease
Seung Joon Choi, Sungjin Yoon, Kyoung-Kon Kim, Doojin Kim, Hye Eun Lee, Kwang Gi Kim, Seung Kak Shin, Ie Byung Park, Seong Min Kim, Dae Ho Lee
Received June 18, 2023  Accepted August 16, 2023  Published online February 1, 2024  
DOI: https://doi.org/10.4093/dmj.2023.0189    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We aimed to evaluate whether composite blood biomarkers including aldo-keto reductase family 1 member B10 (AKR1B10) and cytokeratin 18 (CK-18; a nonalcoholic steatohepatitis [NASH] marker) have clinically applicable performance for the diagnosis of NASH, advanced liver fibrosis, and high-risk NASH (NASH+significant fibrosis).
Methods
A total of 116 subjects including healthy control subjects and patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were analyzed to assess composite blood-based and imaging-based biomarkers either singly or in combination.
Results
A composite blood biomarker comprised of AKR1B10, CK-18, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) showed excellent performance for the diagnosis of, NASH, advanced fibrosis, and high-risk NASH, with area under the receiver operating characteristic curve values of 0.934 (95% confidence interval [CI], 0.888 to 0.981), 0.902 (95% CI, 0.832 to 0.971), and 0.918 (95% CI, 0.862 to 0.974), respectively. However, the performance of this blood composite biomarker was inferior to that various magnetic resonance (MR)-based composite biomarkers, such as proton density fat fraction/MR elastography- liver stiffness measurement (MRE-LSM)/ALT/AST for NASH, MRE-LSM+fibrosis-4 index for advanced fibrosis, and the known MR imaging-AST (MAST) score for high-risk NASH.
Conclusion
Our blood composite biomarker can be useful to distinguish progressive forms of NAFLD as an initial noninvasive test when MR-based tools are not available.
Metabolic Risk/Epidemiology
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Magnetic Resonance-Based Assessments Better Capture Pathophysiologic Profiles and Progression in Nonalcoholic Fatty Liver Disease
Seung Joon Choi, Seong Min Kim, Yun Soo Kim, Oh Sang Kwon, Seung Kak Shin, Kyoung Kon Kim, Kiyoung Lee, Ie Byung Park, Cheol Soo Choi, Dong Hae Chung, Jaehun Jung, MunYoung Paek, Dae Ho Lee
Diabetes Metab J. 2021;45(5):739-752.   Published online October 28, 2020
DOI: https://doi.org/10.4093/dmj.2020.0137
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  • 13 Web of Science
  • 16 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • A Novel Score Based on Controlled Attenuation Parameter Accurately Predicts Hepatic Steatosis in Individuals With Metabolic Dysfunction Associated Steatotic Liver Disease: A Derivation and Independent Validation Study
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    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
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    Dorotea Bozic, Kristian Podrug, Ivana Mikolasevic, Ivica Grgurevic
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Review
Guideline/Fact Sheet
Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association
Byung-Wan Lee, Yong-ho Lee, Cheol-Young Park, Eun-Jung Rhee, Won-Young Lee, Nan-Hee Kim, Kyung Mook Choi, Keun-Gyu Park, Yeon-Kyung Choi, Bong-Soo Cha, Dae Ho Lee, Korean Diabetes Association (KDA) Fatty Liver Research Group
Diabetes Metab J. 2020;44(3):382-401.   Published online May 11, 2020
DOI: https://doi.org/10.4093/dmj.2020.0010
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  • 43 Web of Science
  • 43 Crossref
AbstractAbstract PDFPubReader   

This clinical practice position statement, a product of the Fatty Liver Research Group of the Korean Diabetes Association, proposes recommendations for the diagnosis, progression and/or severity assessment, management, and follow-up of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NAFLD have an increased risk of non-alcoholic steatohepatitis (NASH) and fibrosis and a higher risk of cardiovascular diseases and diabetic complications compared to those without NAFLD. With regards to the evaluation of patients with T2DM and NAFLD, ultrasonography-based stepwise approaches using noninvasive biomarker models such as fibrosis-4 or the NAFLD fibrosis score as well as imaging studies such as vibration-controlled transient elastography with controlled attenuation parameter or magnetic resonance imaging-proton density fat fraction are recommended. After the diagnosis of NAFLD, the stage of fibrosis needs to be assessed appropriately. For management, weight reduction achieved by lifestyle modification has proven beneficial and is recommended in combination with antidiabetic agent(s). Evidence that some antidiabetic agents improve NAFLD/NASH with fibrosis in patients with T2DM is emerging. However, there are currently no definite pharmacologic treatments for NAFLD in patients with T2DM. For specific cases, bariatric surgery may be an option if indicated.

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Corrigendum
Corrigenda: Table Correction. Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis
Yong-ho Lee, Yongin Cho, Byung-Wan Lee, Cheol-Young Park, Dae Ho Lee, Bong-Soo Cha, Eun-Jung Rhee
Diabetes Metab J. 2019;43(5):731-731.   Published online October 24, 2019
DOI: https://doi.org/10.4093/dmj.2019.0188
Corrects: Diabetes Metab J 2019;43(1):31
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Citations

Citations to this article as recorded by  
  • Association of statins with nonalcoholic fatty liver disease in patients with diabetes
    Raj Shah, Alexander Kong, Silvio De Melo, Moheb Boktor, Richard Henriquez, Amar Mandalia, Hrishikesh Samant, Carlos A. Alvarez, Ishak A. Mansi
    Journal of Investigative Medicine.2024;[Epub]     CrossRef
Reviews
Clinical Diabetes & Therapeutics
Nonalcoholic Fatty Liver Disease and Diabetes: Part II: Treatment
Kyung-Soo Kim, Byung-Wan Lee, Yong Jin Kim, Dae Ho Lee, Bong-Soo Cha, Cheol-Young Park
Diabetes Metab J. 2019;43(2):127-143.   Published online April 15, 2019
DOI: https://doi.org/10.4093/dmj.2019.0034
  • 8,066 View
  • 147 Download
  • 28 Web of Science
  • 37 Crossref
AbstractAbstract PDFPubReader   

Nonalcoholic fatty liver disease (NAFLD) and diabetes are common metabolic disorders that are often comorbid conditions. Among many proposed treatments, weight reduction is the only approved option for NAFLD to date. However, it is not easy to maintain weight loss by lifestyle modification alone; pharmacological treatments are helpful in this regard. Although many drugs have been investigated, pioglitazone could be a first-line therapy in patients with NAFLD and diabetes. Many more drugs are currently being developed and investigated, and it is likely that combination strategies will be used for future treatment of NAFLD and diabetes. Attention should be paid to the management of NAFLD and diabetes and efforts should be made to intervene early and individualize treatment of NAFLD in patients with diabetes.

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Complications
Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis
Yong-ho Lee, Yongin Cho, Byung-Wan Lee, Cheol-Young Park, Dae Ho Lee, Bong-Soo Cha, Eun-Jung Rhee
Diabetes Metab J. 2019;43(1):31-45.   Published online December 17, 2018
DOI: https://doi.org/10.4093/dmj.2019.0011
Correction in: Diabetes Metab J 2019;43(5):731
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AbstractAbstract PDFPubReader   

Nonalcoholic fatty liver disease (NAFLD) and diabetes are common metabolic disorders whose prevalence rates are expected to rise worldwide, corresponding to aging and increasingly obese populations. Compared to the general population (around 25%), 50% to 70% of people with diabetes have NAFLD, and NAFLD severity (including fibrosis) tends to be worsened by the presence of diabetes. NAFLD is considered an emerging risk factor for type 2 diabetes mellitus and a contributor to the development of chronic diabetes-related complications. This reciprocal relationship demonstrates the importance of confirming suspected NAFLD in patients with diabetes. Due to the invasive nature of liver biopsy to assess NAFLD status, various alternative non-invasive modalities have been developed and validated. Here, we summarized the epidemiology of NAFLD in patients with diabetes and reviewed currently available imaging modalities and biomarker-based prediction models for their ability to detect liver steatosis and/or fibrosis.

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Letter
Letter: Increased Risk of Hospitalization for Heart Failure with Newly Prescribed Dipeptidyl Peptidase-4 Inhibitors and Pioglitazone Using the Korean Health Insurance Claims Database (Diabetes Metab J 2015;39:247-52)
Dae Ho Lee
Diabetes Metab J. 2015;39(4):348-349.   Published online August 17, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.4.348
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Editorial
Lipoproteins and β-Cell Functions: From Basic to Clinical Data
Dae Ho Lee
Diabetes Metab J. 2014;38(4):274-277.   Published online August 20, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.4.274
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Original Articles
Clinical Characteristics of Type 2 Diabetes Patients according to Family History of Diabetes
Seung Uk Jeong, Dong Gu Kang, Dae Ho Lee, Kang Woo Lee, Dong-Mee Lim, Byung Joon Kim, Keun-Yong Park, Hyoun-Jung Chin, Gwanpyo Koh
Korean Diabetes J. 2010;34(4):222-228.   Published online August 31, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.4.222
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AbstractAbstract PDFPubReader   
Background

Type 2 diabetes mellitus (T2DM) has a strong genetic component, and its prevalence is notably increased in the family members of T2DM patients. However, there are few studies about the family history of T2DM. We carried out this study to assess the influences of family history on clinical characteristics in T2DM patients.

Methods

This is a cross-sectional study involving 651 T2DM patients. Patient history and physical examination were performed and fasting blood was taken. If any first degree relative was diabetic, a family history of diabetes was considered to exist.

Results

Among the total 621 patients, 38.4% had a family history of diabetes. Patients with a family history had a younger age, higher weight, younger age at diagnosis and higher triglyceride level than did those without a family history. Dyslipidemia medication and metabolic syndrome were more prevalent in familial diabetes. Sex, blood pressure, previous treatment for diabetes, HbA1c, C-peptide, total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol were not different between familial and non-familial diabetes. Upon multiple linear regression analysis, the family history of diabetes remained significantly associated with serum triglyceride level.

Conclusion

In T2DM patients with a family history of diabetes, the disease tended to develop earlier. Metabolic syndrome and cardiovascular risk factors are more prevalent in familial T2DM than they were in non-familial T2DM. These results support the necessity of earlier screening for diabetes in family members of T2DM patients and more active prevention against cardiovascular disease in T2DM patients with a family history.

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A Nationwide Survey about the Current Status of Glycemic Control and Complications in Diabetic Patients in 2006: The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus.
Soo Lim, Dae Jung Kim, In Kyung Jeong, Hyun Shik Son, Choon Hee Chung, Gwanpyo Koh, Dae Ho Lee, Kyu Chang Won, Jeong Hyun Park, Tae Sun Park, Jihyun Ahn, Jaetaek Kim, Keun Gyu Park, Seung Hyun Ko, Yu Bae Ahn, Inkyu Lee
Korean Diabetes J. 2009;33(1):48-57.   Published online February 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.1.48
  • 2,875 View
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  • 43 Crossref
AbstractAbstract PDF
BACKGROUND
The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus performed a nationwide survey about the current status of glycemic control and diabetic complications in 2006. METHODS: The current study included 5,652 diabetic patients recruited from the rosters of endocrinology clinics of 13 tertiary hospitals in Korea. Age, gender, height, weight, waist circumference and blood pressure were investigated by standard method. Fasting and postprandial 2 hour glucose, glycosylated hemoglobin (HbA1c), lipid profiles, fasting insulin and c-peptide levels were measured. Microvascular (microalbuminuria, retinopathy and neuropathy) and macrovascular (coronary artery disease [CAD], cerebrovascular disease [CVD] and peripheral artery disease [PAD]) complications were reviewed in their medical records. RESULTS: Mean age of total subjects was 58.7 (+/- 11.6) years and duration of diabetes was 8.8 (0~50) years. Mean fasting and postprandial 2 hour glucose levels were 145.9 +/- 55.0 and 208.0 +/- 84.4 mg/dL, respectively. Their mean HbA1c was 7.9 +/- 1.9%: the percentage of patients within target goal of glycemic control (< 7% of HbA1c) was 36.7%. In this study, 30.3%, 38.3% and 44.6% of patients was found to have microalbuminuria, retinopathy and nephropathy, respectively. Prevalence of CAD, CVD and PAD was 8.7%, 6.7% and 3.0%, respectively. Diabetic complications were closely related with age, duration of diabetes and glycemic control, and this relationship was stronger in microvascular complications than macrovascular ones. CONCLUSION: Only about one third of patients with diabetes was found to reach target glycemic control in tertiary hospitals of Korea. More tight control is needed to reduce deleterious complications of diabetes in Korea.

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Prevalence of the Metabolic Syndrome in Type 2 Diabetic Patients.
Tae Ho Kim, Dae Jung Kim, Soo Lim, In Kyung Jeong, Hyun Shik Son, Choon Hee Chung, Gwanpyo Koh, Dae Ho Lee, Kyu Chang Won, Jeong Hyun Park, Tae Sun Park, Jihyun Ahn, Jaetaek Kim, Keun Gyu Park, Seung Hyun Ko, Yu Bae Ahn, Inkyu Lee
Korean Diabetes J. 2009;33(1):40-47.   Published online February 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.1.40
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AbstractAbstract PDF
BACKGROUND
The aim of this study was to analyze the prevalence of metabolic syndrome in Korean type 2 diabetic patients. METHODS: A total of 4,240 diabetic patients (male 2,033, female 2,207; mean age 58.7 +/- 11.3 years; DM duration 8.9 +/- 7.6 years) were selected from the data of endocrine clinics of 13 university hospitals in 2006. Metabolic syndrome was defined using the criteria of the American Heart Association/National Heart Lung and Blood Institute and the criteria of waist circumference from the Korean Society for the Study of Obesity. RESULTS: The prevalence of metabolic syndrome was 77.9% (76.7% of males, 78.9% of females). The average number of the components of metabolic syndrome was 2.4 +/- 1.1. Abdominal obesity was seen in 56.8% of the patients, hypertriglyceridemia in 42.0%, low HDL cholesterol in 65.1%, and high blood pressure in 74.9%. Abdominal obesity and high blood pressure were much more prevalent among females than males, and low HDL cholesterol was much more prevalent among males than females. The prevalence of metabolic syndrome was not different according to the duration of diabetes. Metabolic syndrome was strongly related with obesity (odds ratio, 6.3) and increased age (odds ratio in the over 70 group, 3.4). CONCLUSION: The prevalence of metabolic syndrome was 77.9% in Korean type 2 diabetic patients. Its prevalence was greater in obese patients and in those over 40 years of age.

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    Seol A Jang, Kyoung Min Kim, Seok Won Park, Chul Sik Kim
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  • Metabolic Age, an Index Based on Basal Metabolic Rate, Can Predict Individuals That are High Risk of Developing Metabolic Syndrome
    Sarahi Vásquez-Alvarez, Sergio K. Bustamante-Villagomez, Gabriela Vazquez-Marroquin, Leonardo M. Porchia, Ricardo Pérez-Fuentes, Enrique Torres-Rasgado, Oscar Herrera-Fomperosa, Ivette Montes-Arana, M. Elba Gonzalez-Mejia
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  • Metabolic syndrome among type 2 diabetic patients in Sub-Saharan African countries: A systematic review and meta-analysis
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    Sa Rah Lee, Ying Han, Ja Won Kim, Ja Young Park, Ji Min Kim, Sunghwan Suh, Mi-Kyoung Park, Hye-Jeong Lee, Duk Kyu Kim
    Diabetes & Metabolism Journal.2012; 36(5): 357.     CrossRef
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    Hye Soon Kim, A Mi Shin, Mi Kyung Kim, Yoon Nyun Kim
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    Ah Young Kang, Su Kyung Park, So Young Park, Hye Jeong Lee, Ying Han, Sa Ra Lee, Sung Hwan Suh, Duk Kyu Kim, Mi Kyoung Park
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Mechanism of 2-Deoxy-D-ribose-induced Damage in Pancreatic beta-cells.
Gwanpyo Koh, Jeong taek Woo, Dae Ho Lee, Seungjoon Oh, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Deok Bae Park
Korean Diabetes J. 2007;31(2):105-112.   Published online March 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.2.105
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AbstractAbstract PDF
BACKGROUND
Mechanism for glucose toxicity is known to be an increased oxidative stress produced by multiple pathways. In our previous report, 2-deoxy-d-ribose (dRib) promoted apoptosis by increasing oxidative stress in a pancreatic beta-cell line. We performed this study to investigate the mechanism of dRib-induced damage of beta-cells. METHODS: HIT-T15 cells were cultured in RPMI-1640 medium with 40 mM dRib for 24 hours after pretreatment with various concentrations of a metal chelator (DTPA) and inhibitors of protein glycation (aminoguanidine and pyridoxamine). Cell viability was determined by MTT assay. Apoptosis was analyzed by flow cytometry with annexin V/PI double staining. RESULTS: DTPA, which inhibits the monosaccharide autoxidation, partially reversed dRib-induced cytotoxicity in a dose-dependent manner (P < 0.01). The cytotoxicity was also suppressed dose-dependently by aminoguanidine (AG) and pyridoxamine (PM) (P < 0.05 and P < 0.01, repectively). Flow cytometric analysis showed that pretreatment of DTPA and AG also reversed the dRib-triggered apoptosis in a dose-dependent manner. We assessed the additional protective effects of inhibitors of protein glycation from dRib-induced cytotoxiciy in the presence of a metal chelator. The additions of AG (P < 0.05) and PM (P < 0.01) significantly reduced the cytotoxicity compared with DTPA alone group. CONCLUSION: This results suggest that dRib produce cytotoxicity and apoptosis through the mechanisms of advanced glycation endproducts (AGEs) formation including the monsaccharide autoxidation and protein glycation in pancreatic beta-cell. Thus, dRib could be a surrogate for glucose in the study of glucose toxicity and chronic diabetic complications.

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    Chi-Deok Park, Hee-Kyung Jung, Chang-Ho Park, Yoo-Seok Jung, Joo-Heon Hong, Hee-Sun Ko, Dong-Hee Kang, Hyun-Soo Kim
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Platelet Aggregability in Type 2 Diabetics.
Chang Hun Lee, Nam Il Cheon, Yeon Sang Lee, Dong Hyeok Cho, Hyun Ho Shin, Jung Min Kim, Dae Ho Lee, Dong Jin Chung, Min Young Chung, Tai Hee Lee
Korean Diabetes J. 2000;24(3):300-309.   Published online January 1, 2001
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AbstractAbstract PDF
BACKGROUND
Increased platelet aggregability is known to be one of the important risk factors for diabetic vascular complications. The relationship between platelet aggregability and diabetic macrovascular complications, varying severity of diabetic microvascular complications and other possible factors was evaluated in Korean adults. METHODS: Platelet aggregability was measured with platelet rich plasma by addition of adenosine diphosphate (ADP) in 45 cases. Normal control group (n=15) was compared with diabetics without macrovascular complications (n=15), diabetics with macrovascular complications (n=15) and several groups divided accoring to the severity of microvascular complications. RESULTS: 1) The mean maximum value of platelet aggregation was 70.3+/-5.3% in control group, and 80.0+/-7.3% in diabetics (p<0.005). 2) The mean maximum value of platelet aggregation was 78.0+/-5.5% in diabetics without macrovascular complications and 83.5+/-7.1% in diabetics with macrovascular complications (p=0.093). 3) The mean maximum value of platelet aggregation was 77.0+/-5.1% in normoproteinuria group, 78.1+/-7.3% in microproteinuria group, and 82.9+/-6.2% in overt proteinuria group (p=0.083). 4) The mean maximum value of platelet aggregation was 77.2+/-6.8% in diabetes without neuropathy group and 82.9+/-6.2% in diabetes with neuropathy group (p=0.114). 5) The mean maximum value of platelet aggregation was 79.3+/-4.9% in diabetes with normal funduscopic findings, 80.2+/-7.3% in diabetes with background retinopathy and 81.6+/-7.9% in diabetes with proliferative retinopathy (p=0.852). 6) Blood glucose showed positive correlations with the mean maximum platelet aggregation ( =0.529, p<0.005). CONCLUSION: The elevated mean maximum value of platelet aggregation was found in diabetics and there were no significant differences between macrovascular complications and between varying severity of retinopathy, neuropathy and proteinuria. Blood glucose showed positive correlations with mean maximum platelet aggregation. Hyperglycemia was a major risk factor affecting platelet aggregation in diabetics and its control may play an important role in prevention of diabetic vascular complications.
A case of NIDDM complicated by acute mediastinitis.
Dae Ho Lee, Ho Cheol Kang, Jae Soo An, Hyun Joo Jang, Eun Jin Choi, Sang Seon Park, Jae Hyun Jho, Min Young Chung, Tai Hee Lee
Korean Diabetes J. 1992;16(3):237-240.   Published online January 1, 2001
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  • 16 Download
AbstractAbstract PDF
No abstract available.

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