Diabetes & Metabolism Journal

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Risk Prediction and Management of Chronic Kidney Disease in People Living with Type 2 Diabetes Mellitus: Ying-Guat Ooi, Tharsini Sarvanandan, Nicholas Ken Yoong Hee, Quan-Hziung Lim, Sharmila S. Paramasivam, Jeyakantha Ratnasingam, Shireene R. Vethakkan, Soo-Kun Lim, Lee-Ling Lim; Diabetes Metab J. 2024;48(2):196-207. Published online January 26, 2024; DOI: https://doi.org/10.4093/dmj.2023.0244

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Abstract PDF Supplementary Material PubReader ePub: People with type 2 diabetes mellitus have increased risk of chronic kidney disease and atherosclerotic cardiovascular disease. Improved care delivery and implementation of guideline-directed medical therapy have contributed to the declining incidence of atherosclerotic cardiovascular disease in high-income countries. By contrast, the global incidence of chronic kidney disease and associated mortality is either plateaued or increased, leading to escalating direct and indirect medical costs. Given limited resources, better risk stratification approaches to identify people at risk of rapid progression to end-stage kidney disease can reduce therapeutic inertia, facilitate timely interventions and identify the need for early nephrologist referral. Among people with chronic kidney disease G3a and beyond, the kidney failure risk equations (KFRE) have been externally validated and outperformed other risk prediction models. The KFRE can also guide the timing of preparation for kidney replacement therapy with improved healthcare resources planning and may prevent multiple complications and premature mortality among people with chronic kidney disease with and without type 2 diabetes mellitus. The present review summarizes the evidence of KFRE to date and call for future research to validate and evaluate its impact on cardiovascular and mortality outcomes, as well as healthcare resource utilization in multiethnic populations and different healthcare settings.

Original Articles

Complications
Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease: Eugene Han, Mi Kyung Kim, Byoung Kuk Jang, Hye Soon Kim; Diabetes Metab J. 2021;45(5):698-707. Published online February 2, 2021; DOI: https://doi.org/10.4093/dmj.2020.0118

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Background
This study aimed to investigate the association between hepatic steatosis burden and albuminuria in Korean patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).
Methods
We recruited 100 patients with both T2DM and NAFLD, but without chronic kidney disease. Albuminuria was defined as a spot urinary albumin-to-creatinine ratio (ACR) ≥30 mg/g. Transient elastography was performed, and the steatosis burden was quantified by controlled attenuation parameter (CAP) with significant steatosis defined as CAP >302 dB/m.
Results
The prevalence of significant steatosis and albuminuria was 56.0% and 21.0%, respectively. Subjects with significant steatosis were significantly younger and had a significantly shorter duration of T2DM, greater waist circumference, and higher body mass index, total cholesterol, triglyceride, and low density lipoprotein cholesterol levels, than subjects without severe NAFLD (all P<0.05). Albuminuria was higher in patients with significant steatosis than in patients without significant steatosis (32.1% vs. 6.8%, P=0.002). Urinary ACR showed a correlation with CAP (r=0.331, P=0.001), and multiple linear regression analysis revealed a significant association between a high degree of albuminuria and high CAP value (r=0.321, P=0.001). Additionally, multivariate logistic regression analysis demonstrated the independent association between urinary ACR and significant steatosis after adjustment for confounding factors including age, body mass index, duration of T2DM, low density lipoprotein level, and renin-angiotensin system blocker use (odds ratio, 1.88; 95% confidence interval, 1.31 to 2.71; P=0.001).
Conclusion
T2DM patients with NAFLD had a higher prevalence of albuminuria, which correlated with their steatosis burden.

Citations

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A Novel Anthropometric Parameter, Weight-Adjusted Waist Index Represents Sarcopenic Obesity in Newly Diagnosed Type 2 Diabetes Mellitus
Min Jeong Park, Soon Young Hwang, Nam Hoon Kim, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo
Journal of Obesity & Metabolic Syndrome.2023; 32(2): 130. CrossRef
Significance of Diabetic Kidney Disease Biomarkers in Predicting Metabolic-Associated Fatty Liver Disease
Jaehyun Bae, Byung-Wan Lee
Biomedicines.2023; 11(7): 1928. CrossRef
Non-alcoholic fatty liver disease and sarcopenia is associated with the risk of albuminuria independent of insulin resistance, and obesity
Eugene Han, Mi Kyung Kim, Seung-Soon Im, Byoung Kuk Jang, Hye Soon Kim
Journal of Diabetes and its Complications.2022; 36(8): 108253. CrossRef
Development and implementation of patient-level prediction models of end-stage renal disease for type 2 diabetes patients using fast healthcare interoperability resources
San Wang, Jieun Han, Se Young Jung, Tae Jung Oh, Sen Yao, Sanghee Lim, Hee Hwang, Ho-Young Lee, Haeun Lee
Scientific Reports.2022;[Epub] CrossRef
Beyond Liver Disease: Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Kidney Disease
Eugene Han
Diabetes & Metabolism Journal.2022; 46(4): 564. CrossRef
Muscle fat contents rather than muscle mass determines nonalcoholic steatohepatitis and liver fibrosis in patients with severe obesity
Eugene Han, Mi Kyung Kim, Hye Won Lee, Seungwan Ryu, Hye Soon Kim, Byoung Kuk Jang, Youngsung Suh
Obesity.2022; 30(12): 2440. CrossRef
Decreased Serum Osteocalcin is an Independent Risk Factor for Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes
Yu-Jie Wang, Chun-Hua Jin, Jiang-Feng Ke, Jun-Wei Wang, Yi-Lin Ma, Jun-Xi Lu, Mei-Fang Li, Lian-Xi Li
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 3717. CrossRef
Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease (Diabetes Metab J 2021;45:698-707)
Eugene Han, Hye Soon Kim
Diabetes & Metabolism Journal.2021; 45(6): 972. CrossRef
Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease (Diabetes Metab J 2021;45:698-707)
Mi-kyung Kim
Diabetes & Metabolism Journal.2021; 45(6): 968. CrossRef
Liver fibrosis indices are related to diabetic peripheral neuropathy in individuals with type 2 diabetes
Kyuho Kim, Tae Jung Oh, Hyen Chung Cho, Yun Kyung Lee, Chang Ho Ahn, Bo Kyung Koo, Jae Hoon Moon, Sung Hee Choi, Hak Chul Jang
Scientific Reports.2021;[Epub] CrossRef

Epidemiology
Lower Leg Fat Depots Are Associated with Albuminuria Independently of Obesity, Insulin Resistance, and Metabolic Syndrome (Korea National Health and Nutrition Examination Surveys 2008 to 2011): Eugene Han, Nan Hee Cho, Mi Kyung Kim, Hye Soon Kim; Diabetes Metab J. 2019;43(4):461-473. Published online March 7, 2019; DOI: https://doi.org/10.4093/dmj.2018.0081

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Abstract PDF PubReader

Background

Although the involvement of obesity in metabolic disorders is well known, leg fat depot influences on albuminuria have not been determined.

Methods

This population-based, cross-sectional study used a nationally representative sample of 2,076 subjects aged ≥20 years from the Korea National Health and Nutrition Examination Surveys of 2008 to 2011. The ratio of leg fat to total fat (LF/TF ratio) was assessed by dual X-ray absorptiometry, and albuminuria was defined as more than one positive dipstick test or an albumin-to-creatinine ratio of ≥30 mg/g.

Results

Individuals whose LF/TF ratio was in the lowest tertile showed a higher proportion of albuminuria than those in the highest tertile (odds ratio [OR], 2.82; 95% confidence interval [CI], 2.01 to 3.96; P<0.001). This association was observed in both sexes, all age groups, and all subgroups stratified by body mass index, waist circumference, homeostasis model assessments of insulin resistance, and the presence of metabolic syndrome (all, P<0.05). Multiple logistic regression analyses also demonstrated that the lowest LF/TF ratio was independently associated with albuminuria risk (OR, 1.55 to 2.16; all, P<0.05). In addition, the risk of albuminuria was higher in sarcopenic individuals with lower LF/TF ratios than in the highest LF/TF ratio subjects without sarcopenia (OR, 3.73; 95% CI, 2.26 to 6.13).

Conclusion

A lower LF/TF ratio was associated with an increased risk of albuminuria independent of obesity, insulin resistance, and metabolic syndrome, and when combined with sarcopenia, the albuminuria risk synergistically increased. Hence, our findings may have implications to improve risk stratification and recommendations on body fat distribution in the general population.

Citations

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Efficacy and safety of evogliptin in patients with type 2 diabetes and non‐alcoholic fatty liver disease: A multicentre, double‐blind, randomized, comparative trial
Eugene Han, Ji Hye Huh, Eun Y. Lee, Ji C. Bae, Sung W. Chun, Sung H. Yu, Soo H. Kwak, Kyong S. Park, Byung‐Wan Lee
Diabetes, Obesity and Metabolism.2022; 24(4): 752. CrossRef
Muscle fat contents rather than muscle mass determines nonalcoholic steatohepatitis and liver fibrosis in patients with severe obesity
Eugene Han, Mi Kyung Kim, Hye Won Lee, Seungwan Ryu, Hye Soon Kim, Byoung Kuk Jang, Youngsung Suh
Obesity.2022; 30(12): 2440. CrossRef
Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease
Eugene Han, Mi Kyung Kim, Byoung Kuk Jang, Hye Soon Kim
Diabetes & Metabolism Journal.2021; 45(5): 698. CrossRef

Complications
Higher Prevalence and Progression Rate of Chronic Kidney Disease in Elderly Patients with Type 2 Diabetes Mellitus: Kyung-Soo Kim, Seok Won Park, Yong-Wook Cho, Soo-Kyung Kim; Diabetes Metab J. 2018;42(3):224-232. Published online May 31, 2018; DOI: https://doi.org/10.4093/dmj.2017.0065

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Abstract PDF PubReader

Background

To evaluate the prevalence of chronic kidney disease (CKD) and progression rate to CKD in elderly patients with type 2 diabetes mellitus (T2DM).

Methods

We investigated the medical records of 190 elderly patients (65 years or older) with T2DM from 2005 to 2011 in 6-month increments. Mean follow-up duration was 64.5 months. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² and/or the presence of albuminuria.

Results

The mean age was 70.4 years and mean diabetes duration was 10.6 years. Among all the participants, 113 patients (59.5%) had CKD. The eGFR was significantly decreased between baseline (65.7±15.0 mL/min/1.73 m²) and the end of follow-up (52.7±17.5 mL/min/1.73 m², P<0.001). At the end of follow-up, the prevalence of eGFR <60 mL/min/1.73 m² had increased by 61.6% (at baseline, 44.2%). Furthermore, in patients with eGFR ≥60 mL/min/1.73 m², the progression rate to more than CKD stage 3 was 39.6% at the end of follow-up; 30.2% of elderly diabetic patients had progressed to albuminuria from normoalbuminuria. Kaplan-Meier analysis showed that the time interval to worsening nephropathy was significantly shorter in elderly patients with diabetes duration ≥10 years than in those with diabetes duration <5 years (P=0.018).

Conclusion

CKD was commonly observed in older patients with T2DM, and the progression rate to CKD is also high. Consequently, it is important to identify and manage CKD as early as possible in elderly patients with T2DM, especially in those with diabetes duration ≥10 years.

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Prevalence and Determinants of Diabetic Nephropathy in Korea: Korea National Health and Nutrition Examination Survey: Jae Hee Ahn, Ji Hee Yu, Seung-Hyun Ko, Hyuk-Sang Kwon, Dae Jung Kim, Jae Hyeon Kim, Chul Sik Kim, Kee-Ho Song, Jong Chul Won, Soo Lim, Sung Hee Choi, Kyungdo Han, Bong-Yun Cha, Nan Hee Kim; Diabetes Metab J. 2014;38(2):109-119. Published online April 18, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.2.109

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Abstract PDF PubReader

Background

Diabetic nephropathy is a leading cause of end stage renal disease and is associated with an increased risk of cardiovascular mortality. It manifests as albuminuria or impaired glomerular filtration rate (GFR), and the prevalence of diabetic nephropathy varies with ethnicity. The prevalence of diabetic nephropathy and its determinants in Korean adults have not previously been studied at the national level. This cross-sectional study was undertaken to ascertain the prevalence and determinants of albuminuria and chronic kidney disease (CKD) in Korean patients with diabetes.

Methods

The Korea National Health and Nutrition Examination Survey (KNHANES) V, conducted in 2011, was used to define albuminuria (n=4,652), and the dataset of KNHANES IV-V (2008-2011) was used to define CKD (n=21,521). Selected samples were weighted to represent the entire civilian population in Korea. Albuminuria was defined as a spot urine albumin/creatinine ratio >30 mg/g. CKD was defined as a GFR <60 mL/min/1.73 m².

Results

Among subjects with diabetes, 26.7% had albuminuria, and 8.6% had CKD. Diabetes was associated with an approximate 2.5-fold increased risk of albuminuria, with virtually no difference between new-onset and previously diagnosed diabetes. Only systolic blood pressure was significantly associated with albuminuria, and old age, high serum triglyceride levels, and previous cardiovascular disease (CVD) were related with CKD in subjects with diabetes.

Conclusion

Korean subjects with diabetes had a higher prevalence of albuminuria and CKD than those without diabetes. Blood pressure was associated with albuminuria, and age, triglyceride level, and previous CVD were independent determinants of CKD in subjects with diabetes.

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Subclinical Hypothyroidism Is Independently Associated with Microalbuminuria in a Cohort of Prediabetic Egyptian Adults: Mervat M. El-Eshmawy, Hala A. Abd El-Hafez, Walaa Othman El Shabrawy, Ibrahim A. Abdel Aal; Diabetes Metab J. 2013;37(6):450-457. Published online December 12, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.6.450

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Abstract PDF PubReader

Background

Recent evidence has suggested an association between subclinical hypothyroidism (SCH) and microalbuminuria in patients with type 2 diabetes. However, whether SCH is related to microalbuminuria among subjects with prediabetes has not been studied. Thus, we evaluated the association between SCH and microalbuminuria in a cohort of prediabetic Egyptian adults.

Methods

A total of 147 prediabetic subjects and 150 healthy controls matched for age and sex were enrolled in this study. Anthropometric measurements, plasma glucose, lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR), thyroid stimulating hormone (TSH), free thyroxine, triiodothyronine levels, and urinary albumin-creatinine ratio (UACR) were assessed.

Results

The prevalence of SCH and microalbuminuria in the prediabetic subjects was higher than that in the healthy controls (16.3% vs. 4%, P<0.001; and 12.9% vs. 5.3%, P=0.02, respectively). Prediabetic subjects with SCH were characterized by significantly higher HOMA-IR, TSH levels, UACR, and prevalence of microalbuminuria than those with euthyroidism. TSH level was associated with total cholesterol (P=0.05), fasting insulin (P=0.01), HOMA-IR (P=0.01), and UACR (P=0.005). UACR was associated with waist circumference (P=0.01), fasting insulin (P=0.05), and HOMA-IR (P=0.02). With multiple logistic regression analysis, SCH was associated with microalbuminuria independent of confounding variables (β=2.59; P=0.01).

Conclusion

Our findings suggest that prediabetic subjects with SCH demonstrate higher prevalence of microalbuminuria than their non-SCH counterparts. SCH is also independently associated with microalbuminuria in prediabetic subjects. Screening and treatment for SCH may be warranted in those patients.

Citations

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The prevalence of subclinical hypothyroidism in a pre-diabetes population and an analysis of related factors
Xingyu Chang, Yaqi Wang, Yi Liu, Yanyu Shen, Jiaqing Feng, Qianqian Liu, Chenjun Jiang, Jing Yu, Xulei Tang, Gaojing Jing, Qianglong Niu, Songbo Fu
Annals of Medicine.2023; 55(1): 643. CrossRef
High Thyroid-Stimulating Hormone and Low Free Triiodothyronine Levels Are Associated with Chronic Kidney Disease in Three Population-Based Studies from Germany
Till Ittermann, Sabrina von Rheinbaben, Marcello R. P. Markus, Marcus Dörr, Antje Steveling, Matthias Nauck, Alexander Teumer, Maik Gollasch, Dominik Spira, Maximilian König, Ilja Demuth, Elisabeth Steinhagen-Thiessen, Henry Völzke, Sylvia Stracke
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Free triiodothyronine predicts the risk of developing diabetic kidney disease
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Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 59. CrossRef
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Gautam Das, Peter N Taylor, Hussam Abusahmin, Amer Ali, Brian P Tennant, John Geen, Onyebuchi Okosieme
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine.2019; 56(1): 155. CrossRef
The longitudinal effect of subclinical hypothyroidism on urine microalbumin-to-urine creatinine ratio in patients with type 2 diabetes mellitus
Juan Xie, Xiaoqing Wang, Yiyuan Zhang, Hailun Li, Yong Xu, Donghui Zheng
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Association between subclinical hypothyroidism and diabetic nephropathy in type 2 diabetes
Ayman Abd-Elrahman Mohamed Nsr-Allah, Azza H. Abd-El Fatah, Mahmoud Azab, Maggie M. Fawzi
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Role of Microalbuminuria in Predicting Cardiovascular Mortality in Individuals With Subclinical Hypothyroidism
Tushar A. Tuliani, Maithili Shenoy, Kevin Belgrave, Abhishek Deshmukh, Sadip Pant, Anthony Hilliard, Luis Afonso
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Salvatore Benvenga, Alessandro Antonelli
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M. Gourine, K. Bentadj, S. Mostefa-Kara, A. Cherrak, S. Halimi, M. Belhadj
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Peng Liu, Ruidong Liu, Xia Chen, Yingying Chen, Debao Wang, Fengmei Zhang, Yangang Wang
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Free Triiodothyronine Levels Are Associated with Diabetic Nephropathy in Euthyroid Patients with Type 2 Diabetes
Jingcheng Wu, Xiaohua Li, Yang Tao, Yufei Wang, Yongde Peng
International Journal of Endocrinology.2015; 2015: 1. CrossRef
Letter: Subclinical Hypothyroidism Is Independently Associated with Microalbuminuria in a Cohort of Prediabetic Egyptian Adults (Diabetes Metab J2013;37:450-7)
In-Kyung Jeong
Diabetes & Metabolism Journal.2014; 38(1): 83. CrossRef
Free Triiodothyronine Concentrations Are Inversely Associated with Microalbuminuria
Yulin Zhou, Lei Ye, Tiange Wang, Jie Hong, Yufang Bi, Jie Zhang, Baihui Xu, Jichao Sun, Xiaolin Huang, Min Xu
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Chronic Kidney Disease and Associated Cardiovascular Risk Factors in Chinese with Type 2 Diabetes: Qing-Lin Lou, Xiao-Jun Ouyang, Liu-Bao Gu, Yong-Zhen Mo, Ronald Ma, Jennifer Nan, Alice Kong, Wing-Yee So, Gary Ko, Juliana Chan, Chun-Chung Chow, Rong-Wen Bian; Diabetes Metab J. 2012;36(6):433-442. Published online December 12, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.6.433

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Background

To determine the frequency of chronic kidney disease (CKD) and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009.

Methods

Patients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m². Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g.

Results

We recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9±12.0 years). The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval) being 1.93 (1.28 to 2.93), 1.70 (1.09 to 2.64), and 1.03 (1.00 to 1.06), respectively.

Conclusion

In conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes.

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Serum Cystatin C Reflects the Progress of Albuminuria: Jeong Seon Yoo, Young Mi Lee, Eun Hae Lee, Ji Woon Kim, Shin Young Lee, Ki-Cheon Jeong, Shin Ae Kang, Jong Suk Park, Joo Young Nam, Chul Woo Ahn, Young Duk Song, Kyung Rae Kim; Diabetes Metab J. 2011;35(6):602-609. Published online December 26, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.6.602

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Abstract PDF PubReader

Background

Research on the relationship between urinary albumin excretion and serum cystatin C in diabetes is restricted to cross-sectional studies. In this study, we investigated how well serial measurements of serum cystatin C level reflect changes in the urinary albumin excretion rate.

Methods

We enrolled and retrospectively collected data on 1,058 participants with type 2 diabetes who were older than 18 years and who had more than 3 years of follow-up with serial measurements of albuminuria and serum cystatin C at an outpatient clinic.

Results

With the use of a linear mixed model, we found that the albuminuria level for each patient over time corresponded with the annual change in serum cystatin C-based estimated glomerular filtration rate (cysC-eGFR) but did not correspond with the creatinine-based eGFR calculated by the modification of diet in renal disease formula (MDRD-eGFR). The discrepancy in the direction of the trend was smaller with cysC-eGFR than with MDRD-eGFR.

Conclusion

Serum cystatin C level reflects the trend in albuminuria level more accurately than serum creatinine level in Korean type 2 diabetes mellitus patients.

Citations

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Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease
Eugene Han, Mi Kyung Kim, Byoung Kuk Jang, Hye Soon Kim
Diabetes & Metabolism Journal.2021; 45(5): 698. CrossRef
Increase of BACE1, Brain-Renal Risk Factor, Contributes to Kidney Damage in an Alzheimer’s Disease Mouse Model
Yan Shi, Feng Gao, Xiaoli Yang, Dongwei Liu, Qiuxia Han, Zhangsuo Liu, Hanyu Zhu, Yong Shen
Journal of Alzheimer's Disease.2020; 76(1): 237. CrossRef
Lower Leg Fat Depots Are Associated with Albuminuria Independently of Obesity, Insulin Resistance, and Metabolic Syndrome (Korea National Health and Nutrition Examination Surveys 2008 to 2011)
Eugene Han, Nan Hee Cho, Mi Kyung Kim, Hye Soon Kim
Diabetes & Metabolism Journal.2019; 43(4): 461. CrossRef
Evaluation of creatinine-based and cystatin C-based equations for estimation of glomerular filtration rate in type 1 diabetic patients
Caroline Pereira Domingueti, Rodrigo Bastos Fóscolo, Ana Cristina Simões e Silva, Luci Maria S. Dusse, Janice Sepúlveda Reis, Maria das Graças Carvalho, Ana Paula Fernandes, Karina Braga Gomes
Archives of Endocrinology and Metabolism.2016; 60(2): 108. CrossRef

Serum Visfatin and Fetuin-A Levels and Glycemic Control in Patients with Obese Type 2 Diabetes Mellitus: Fethiye Oztop Gunduz, Sembol Turkmen Yildirmak, Mustafa Temizel, Yilmaz Faki, Mustafa Cakmak, Mustafa Durmuscan, Funda Sezgin; Diabetes Metab J. 2011;35(5):523-528. Published online October 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.5.523

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Abstract PDF PubReader

Background

Visfatin is an adipokine produced by visceral adipose tissue and has insulin-mimicking effects. Fetuin-A is a hepatic secretory protein that binds the insulin receptor and inhibits insulin action both in vivo and in vitro. The authors of the present study aimed to investigate the levels of serum visfatin and fetuin-A and their correlation with hemoglobin A1c (HbA1c) and urine albumin levels in patients with type 2 diabetes mellitus (T2DM).

Methods

A total of 40 obese patients with T2DM (11 males and 29 females; age, 54.47±10.83 years and 23 obese nondiabetic controls (8 males and 15 females; age, 53.04±11.33 years) were included in the study. Age, sex, and body mass index were similar in the 2 groups. Serum visfatin and fetuin-A levels were measured by enzyme-linked immunosorbent assay. HbA1c and urine albumin levels were measured by high performance liquid chromatography and nephelometric method, respectively.

Results

Serum levels of visfatin in patients with T2DM (4.03±2.44 ng/mL) were similar to the control group (3.65±3.02 ng/mL). Serum fetuin-A levels were significantly lower in patients with T2DM than the controls (298.75±78.86 and 430.73±94.46 µg/mL, respectively). HbA1c levels were significantly higher in the T2DM group compared with controls (7.33±1.32 and 5.44±0.84%, respectively). Correlations between visfatin, fetuin-A and HbA1c levels were not observed.

Conclusion

The present study suggests fetuin-A may play a role in the pathogenesis of T2DM.

Citations

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Assessment of serum and salivary visfatin levels in newly diagnosed patients of type-II DM
Faith R. Jerusha, Vandana Raghunath
Journal of Oral and Maxillofacial Pathology.2023; 27(4): 663. CrossRef
Evaluation of the serum visfatin eotaxin and fetuin-A levels of patients with type 2 diabetes mellitus
Hacer KAYHAN KAYA, Abdurrahman ŞERMET, Zafer PEKKOLAY, Ezel TAŞDEMİR, Dilek AYGÜN KEŞİM
Anatolian Current Medical Journal.2022; 4(1): 113. CrossRef
The Association Between Three Adipocytokines (Adiponectin, Resistin and Visfatin) And Thyroid Status in Patients With Type 2 Diabetes Mellitus and Autoimmune Thyroiditis
Š. Sotak, Z. Schroner, I. Lazúrová, M. Felšőci, I. Jochmanová, D. Petrášová, I. Bertková, M. Mitníková, B. Nováková, H. Wagnerová, O. Bobelová
Physiological Research.2021; (6): 865. CrossRef
Prediction of gestational diabetes mellitus in the first trimester: comparison of maternal fetuin-A, N-terminal proatrial natriuretic peptide, high-sensitivity C-reactive protein, and fasting glucose levels
Hatice Kansu-Celik, A. Seval Ozgu-Erdinc, Burcu Kisa, Rahime Bedir Findik, Canan Yilmaz, Yasemin Tasci
Archives of Endocrinology and Metabolism.2019;[Epub] CrossRef
The association between circulating fetuin-A levels and type 2 diabetes mellitus risk: systematic review and meta-analysis of observational studies
F. Roshanzamir, M. Miraghajani, M. H. Rouhani, M. Mansourian, R. Ghiasvand, S. M. Safavi
Journal of Endocrinological Investigation.2018; 41(1): 33. CrossRef
Fetuin-A level in type 2 diabetic patients: relation to microvascular complications
Nehal H. Al-Said, Fatma M. Taha, Ghada M. Abdel-Aziz, Marwa S. Abdel-Tawab
The Egyptian Journal of Internal Medicine.2018; 30(3): 121. CrossRef
Serum levels of fetuin A are increased in women with gestational diabetes mellitus
Ozlem Turhan Iyidir, Ceyla Konca Degertekin, Banu Aktas Yilmaz, Alev E. Altinova, Fusun B. Toruner, Nuray Bozkurt, Goksun Ayvaz, Mujde Akturk
Archives of Gynecology and Obstetrics.2015; 291(4): 933. CrossRef
Lower Fetuin-A, Retinol Binding Protein 4 and Several Metabolites after Gastric Bypass Compared to Sleeve Gastrectomy in Patients with Type 2 Diabetes
Mia Jüllig, Shelley Yip, Aimin Xu, Greg Smith, Martin Middleditch, Michael Booth, Richard Babor, Grant Beban, Rinki Murphy, Pankaj K. Singh
PLoS ONE.2014; 9(5): e96489. CrossRef
Preventive roles of swimming exercise and pioglitazone treatment on hepatic dysfunction in a rat model of metabolic syndrome
Hussein F. Sakr, Fahaid H. Al-Hashem, Waffaa M. Hassab El-Naby, Mahmoud A. Alkhateeb, Mohamed Samir A. Zaki, Hesham M. El Refaey, Mohamed D. Morsy
Canadian Journal of Physiology and Pharmacology.2014; 92(2): 162. CrossRef
Relationship between circulating visfatin/NAMPT, nutritional status and insulin resistance in an elderly population – results from the PolSenior substudy
Magdalena Olszanecka-Glinianowicz, Aleksander Owczarek, Maria Bożentowicz-Wikarek, Aniceta Brzozowska, Małgorzata Mossakowska, Tomasz Zdrojewski, Tomasz Grodzicki, Andrzej Więcek, Jerzy Chudek
Metabolism.2014; 63(11): 1409. CrossRef

Homocysteine as a Risk Factor for Development of Microalbuminuria in Type 2 Diabetes: Eun-Hee Cho, Eun Hee Kim, Won Gu Kim, Eun Hui Jeong, Eun Hee Koh, Woo-Je Lee, Min-Seon Kim, Joong-Yeol Park, Ki-Up Lee; Korean Diabetes J. 2010;34(3):200-206. Published online June 30, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.3.200

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Abstract PDF PubReader

Background

Kidney function is critical in homocysteine clearance, and plasma homocysteine level is frequently increased in patients with renal failure. On the other hand, recent studies in animals have shown that hyperhomocysteinemia induces renal injury. In this study, we determined whether hyperhomocysteinemia can be a risk factor for the development of microalbuminuria in patients with type 2 diabetes.

Methods

A nested case-control study. Of 887 patients with type 2 diabetes who did not have microalbuminuria at baseline, 76 developed microalbuminuria during follow-up (mean, 36.0 ± 11.7 months; range, 18 to 76 months). The control group consisted of 152 age- and sex-matched subjects who did not develop microalbuminuria. Baseline plasma homocysteine concentrations were measured in stored samples.

Results

Baseline plasma homocysteine concentrations and mean HbA1C levels during follow-up were significantly higher in patients who developed microalbuminuria than in those who remained normoalbuminuric. Multivariate logistic regression analysis showed that baseline plasma homocysteine level and mean HbA1C were independent predictors of microalbuminuria in type 2 diabetes.

Conclusion

Hyperhomocysteinemia was associated with increased risk of microalbuminuria in patients with type 2 diabetes supporting the concept that hyperhomocysteinemia has an etiologic role in the pathogenesis of diabetic nephropathy.

Citations

Citations to this article as recorded by

Homocysteine and diabetes: Role in macrovascular and microvascular complications
Emir Muzurović, Ivana Kraljević, Mirsala Solak, Siniša Dragnić, Dimitri P. Mikhailidis
Journal of Diabetes and its Complications.2021; 35(3): 107834. CrossRef
Associations of Homocysteine with B Vitamins and Zinc in Serum Levels of Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study
Sadako MATSUI, Chika HIRAISHI, Ryo SATO, Takai KOJIMA, Kiyotaka ANDO, Kei FUJIMOTO, Hiroshi YOSHIDA
Journal of Nutritional Science and Vitaminology.2021; 67(6): 417. CrossRef
A risk scoring system for the decreased glomerular filtration rate in Chinese general population
Yan Gu, Min Chen, Bei Zhu, Xiaohua Pei, Zhenzhu Yong, Xiaona Li, Qun Zhang, Weihong Zhao
Journal of Clinical Laboratory Analysis.2020;[Epub] CrossRef
Relationship between plasma total homocysteine and the severity of renal function in Chinese patients with type 2 diabetes mellitus aged ≥75 years
Ning Ma, Ning Xu, Dong Yin, Weiwei Liu, Mengping Wu, Xingbo Cheng
Medicine.2020; 99(27): e20737. CrossRef
Correlation between serum homocysteine level and ulcerative colitis: A meta-analysis
Yifang Zhong, Feng Yan, Weixia Jie, Ying Zhou, Fang Fang
Pteridines.2019; 30(1): 114. CrossRef
The role of molecular genetic alterations in genes involved in folate and homocysteine metabolism in multifactorial diseases pathogenesis
A. M. Burdennyy, V. I. Loginov, T. M. Zavarykina, E. A. Braga, A. A. Kubatiev
Russian Journal of Genetics.2017; 53(5): 528. CrossRef
МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИЕ НАРУШЕНИЯ ГЕНОВ ФОЛАТНОГО И ГОМОЦИСТЕИНОВОГО ОБМЕНА В ПАТОГЕНЕЗЕ РЯДА МНОГОФАКТОРНЫХ ЗАБОЛЕВАНИЙ, "Генетика"
А. М. Бурдённый, В.И. Логинов, Т.М. Заварыкина, Э.А. Брага, А.А. Кубатиев
Генетика.2017; (5): 526. CrossRef
Association Between Plasma Homocysteine and Microalbuminuria in Untreated Patients with Essential Hypertension: a Case-Control Study
Ze-min Kuang, Ying Wang, Shu-jun Feng, Long Jiang, Wen-li Cheng
Kidney and Blood Pressure Research.2017; 42(6): 1303. CrossRef
NMDA Receptors as Potential Therapeutic Targets in Diabetic Nephropathy: Increased Renal NMDA Receptor Subunit Expression in Akita Mice and Reduced Nephropathy Following Sustained Treatment With Memantine or MK-801
Hila Roshanravan, Eun Young Kim, Stuart E. Dryer
Diabetes.2016; 65(10): 3139. CrossRef
Association between homocysteine status and the risk of nephropathy in type 2 diabetes mellitus
Song Mao, Wei Xiang, Songming Huang, Aihua Zhang
Clinica Chimica Acta.2014; 431: 206. CrossRef
Prevalence and Determinants of Diabetic Nephropathy in Korea: Korea National Health and Nutrition Examination Survey
Jae Hee Ahn, Ji Hee Yu, Seung-Hyun Ko, Hyuk-Sang Kwon, Dae Jung Kim, Jae Hyeon Kim, Chul Sik Kim, Kee-Ho Song, Jong Chul Won, Soo Lim, Sung Hee Choi, Kyungdo Han, Bong-Yun Cha, Nan Hee Kim
Diabetes & Metabolism Journal.2014; 38(2): 109. CrossRef
Plasma Homocysteine level and its clinical correlation with type 2 diabetes mellitus and its complications
Satyendra Kumar Sonkar, Gyanendra Kumar Sonkar, Deepika Soni, Dheeraj Soni, Kauser Usman
International Journal of Diabetes in Developing Countries.2014; 34(1): 3. CrossRef
Genetic Predisposition for Development of Nephropathy in Type 2 Diabetes Mellitus
Ravindra Kumar, Raj Kumar Sharma, Sarita Agarwal
Biochemical Genetics.2013; 51(11-12): 865. CrossRef
Is C677T Polymorphism in Methylenetetrahydrofolate Reductase Gene a Risk Factor for Diabetic Nephropathy or Diabetes Mellitus in a Chinese Population?
Wen-peng Cui, Bing Du, Ye Jia, Wen-hua Zhou, Sheng-mao Liu, Ying-chun Cui, Fu-zhe Ma, Ping Luo, Li-ning Miao
Archives of Medical Research.2012; 43(1): 42. CrossRef
The role of coagulation and inflammation in the development of diabetic nephropathy in patients withdiabetes mellitus type 2
Yulia Valer'evna Khasanova, Alsu Asatovna Nelaeva, Anna Borisovna Galkina, Irina Vasil'evna Medvedeva
Diabetes mellitus.2012; 15(1): 31. CrossRef

Association of Spot Urine Albumin-to-Creatinine Ratio and 24 Hour-Collected Urine Albumin Excretion Rate in Patients with Type 2 Diabetes Mellitus.: Jee In Lee, Hyuk Sang Kwon, Su Jin Oh, Jung Min Lee, Sang Ah Chang, Bong Yun Cha, Hyun Shik Son, Tae Seo Sohn; Korean Diabetes J. 2009;33(4):299-305. Published online August 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.4.299

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Abstract PDF: BACKGROUND
Measuring urine albumin in diabetic patients is an important screening test to identify those individuals at high risk for cardiovascular disease and the progression of kidney disease. Recently, spot urine albumin-to-creatinine ratio (ACR) has replaced 24 hour-collected urine albumin excretion rate (AER) as a screening test for microalbuminuria given its comparative simplicity. The purpose of the current study was to evaluate the degree of correlation between AER and ACR in the normal, microalbuminuric and macroalbuminuric ranges, and to identify the lower limits of ACR for both genders. METHODS: A total of 310 type 2 diabetics admitted to one center were enrolled in the present study. Following the collection of a spot urine sample, urine was collected for 24 hours and albumin content was measured in both specimens. RESULTS: Mean patient age was 60.2 years. A total of 25.4% had microalbuminuria and 15.8% had macroalbuminuria. The data revealed a strongly positive correlation between AER and ACR across all ranges of albuminuria (R = 0.8). The cut-off value of ACR for 30 mg/day of AER by the regression equation was 24 microgram/mg for men, 42 microgram/mg for women and 31.2 microgram/mg for all patients. The diagnostic performance expressed as the area under the curve (AUC) was 0.938 (95% CI, 0.911-0.965) for ACR. ACR revealed a sensitivity of 84% and specificity of 84%, when a cut-off value of 31.2 microgram/mg was employed. CONCLUSION: ACR was highly correlated with AER, particularly in the range of microalbuminuria. The gender combined cut-off value of ACR in type 2 diabetic patients was determined to be 31.2 microg/mg However, additional studies of large outpatient populations, as opposed to the inpatient population used in the present study, are required to confirm the utility of this value.

The Association Between Urinary Albumin to Creatinine Ratio and Coronary Artery Calcification in Type 2 Diabetic Patients.: Ju Young Lee, Yeon Kyung Choi, Hyun Ae Seo, Jae Han Jeon, Jung Eun Lee, Seong Su Moon, Jung Guk Kim, Bo Wan Kim, In Kyu Lee; Korean Diabetes J. 2009;33(4):289-298. Published online August 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.4.289

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Abstract PDF: BACKGROUND
Atherosclerosis, the most common cause of death in type 2 diabetic patients, is closely associated with coronary artery calcium deposition. The coronary calcifications can be easily measured using coronary calcium scoring computed tomography (CT). And microalbuminuria is known as an independent risk factor of cardiovascular disease. So, we examined the association of urinary albumin to creatinine ratio (UACR) and coronary calcification score (CCS) in type 2 diabetic patients. METHODS: Among type 2 diabetic patients who underwent the multidetector CT scanning for the evaluation of CCS at Kyungpook National University Hospital between December 2007 and May 2008, 155 subjects were included. CCS, demographic and laboratory data were assessed. RESULTS: Coronary artery calcifications were identified in 90 patients (51%) and mean, median CCS was 205.8 +/- 476.9, 8.74 (0, 132.0). 60 subjects revealed UACR greater than 30 ug/mg. With the UACR increment, CCS revealed a significant increase (P < 0.001). Age, duration of diabetes, serum Apo A1 level, serum high sensitivity C-reactive protein (hs-CRP) level were also associated with CCS. However, after adjusting for age, UACR and CCS exhibited a significant positive relationship (P = 0.002). CONCLUSION: Increased UACR is associated with coronary artery calcification in type 2 diabetic patients and these results will be useful in early evaluating the presence of macrovascular complications in these patients.

Frequency of Silent Myocardial Ischemia Detected by Thallium-201 SPECT in Patients with Type 2 Diabetes.: Dong Woo Kim, Eun Hee Jung, Eun Hee Koh, Min Seon Kim, Joong Yeol Park, Seung Whan Lee, Seong Wook Park, Jin Sook Ryu, Ki Up Lee; Korean Diabetes J. 2009;33(3):225-231. Published online June 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.3.225

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Abstract PDF: BACKGROUND
Silent myocardial ischemia (SMI) is more common in diabetic patients than among the general population. It is not yet established whether a routine screening test for SMI is necessary, and which screening test would be most useful. The purpose of this study was to estimate the prevalence of SMI detected by Thallium-201 perfusion single photon emission computed tomography (SPECT) in type 2 diabetic patients. METHODS: A total of 173 asymptomatic type 2 diabetic patients were included in the study. Thallium-201 perfusion SPECT was performed to screen for SMI. RESULTS: Among the 173 patients, abnormal perfusion patterns were found in 11 patients. Coronary angiography was carried out for these patients, and significant coronary artery stenosis was found in ten of them (positive predictive value; 90.9%). There was a significant association between SMI and overt albuminuria (OR = 7.33, 95% CI, 1.825-29.437). CONCLUSION: Thallium-201 perfusion SPECT is not sensitive enough to identify SMI, but is accurate in detecting decreased myocardial perfusion. This may be a useful screening tool for detecting SMI in type 2 diabetic patients with impaired renal function.

Clinical Significance of Decreased Glomerular Filtration Rate (GFR) without Albuminuria among Type 2 Diabetics.: Ji Eun Lee, Kyu Chang Won, Hyoung Woo Lee, Ji Sung Yoon; Korean Diabetes J. 2008;32(3):252-258. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.3.252

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Abstract PDF

BACKGROUND
Microalbuminuria in type 2 diabetes is a predictor of development of clinical nephropathy and cardiovascular disease. But, it has been reported that reduced glomerular filtration rate (GFR) may occur in some normoalbuminuric diabetic patients. The aim of this study was to identify whether decreased GFR without microalbuminuria is to predict diabetic vascular complications. METHODS: Between January 1998 and February 2001, 73 patients with type 2 diabetes who visited Yeungnam university medical center were divided into 5 groups according to initial GFR ranges: group 1 (GFR < 30 mL/min), group 2 (30 < or = GFR < 60 mL/min), group 3 (60 < or = GFR < 90 mL/min), group 4 (90 < or = GFR < 125 mL/min), group 5 (125 mL/min < or = GFR). They were examined for microvascular and macrovascular complications initially and after 4 years. RESULTS: Decreased GFR had a negative correlation with age (r = -0.472, P = 0.001). Decreased GFR without microalbuminuria had a significant correlation with development of diabetic nephropathy (P = 0.016) after 4 years. There were no significant correlation with the prevalence of diabetic retinopathy, peripheral neuropathy, and macrovacular disease. But, our study showed that coronary artery disease had an increasing tendency with decreased GFR without statistical significance (P = 0.085). CONCLUSIONS: Our data suggest that reduced GFR, independent of albuminuria, may be an important predictor of diabetic nephropathy and coronary artery disease to some extent. So we recommend that not only the microalbuminuria, but also the decrease in GFR should be evaluated at the follow-up of patients with type 2 diabetes.

Citations

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Screening and Management of Diabetic Nephropathy
Ji Sung Yoon
The Journal of Korean Diabetes.2013; 14(1): 19. CrossRef

Review

The Role of Glomerular Podocytes in Diabetic Nephropathy.: Eun Young Lee, Choon Hee Chung; Korean Diabetes J. 2007;31(6):451-454. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.451

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Abstract PDF

Diabetic nephropathy is the most common cause of end-stage renal disease and accounts for significant morbidity and mortality among individuals with diabetes mellitus. Therefore, the clarification of the pathogenesis of diabetic nephropathy is an urgent issue. Podocytes cover the outer layer of the glomerulus and maintain its integrity so that fluid and toxins exit in urine, but cells and important proteins are kept in the blood stream. Diabetes mellitus alters this structure, it becomes scarred and then the ability of the kidney to clear toxins is lost. Recent evidence shows that early in diabetes the podocyte number is reduced, areas of the glomerular basement membrane are denuded, and podocyte number predicts long-term urinary albumin excretion in the patients with diabetes and microalbuminuria. These results suggest that podocytes play a critical role in the early stage of diabetic nephropathy. It is the purpose of this article to review the pathogenetic role of podocytes in diabetic nephropathy.

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Isabella F.D. Pinto, Railmara P. Silva, Adriano de B. Chaves Filho, Lucas S. Dantas, Vanderson S. Bispo, Isaac A. Matos, Felipe A.M. Otsuka, Aline C. Santos, Humberto Reis Matos
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Experimental and Molecular Medicine.2011; 43(12): 676. CrossRef

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