Diabetes & Metabolism Journal

Original Articles

Metabolic Risk/Epidemiology
Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus: Hokyou Lee, Gyuri Kim, Young Ju Choi, Byung Wook Huh, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Eun Jig Lee, Yong-ho Lee, Kap Bum Huh; Diabetes Metab J. 2020;44(2):267-276. Published online February 28, 2019; DOI: https://doi.org/10.4093/dmj.2019.0001

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Background

Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM.

Methods

We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography.

Results

LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002).

Conclusions

Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.

Citations

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Anna G. Hoek, Elisa Dal Canto, Eva Wenker, Navin Bindraban, M. Louis Handoko, Petra J. M. Elders, Joline W. J. Beulens
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Dániel Kucsera, Mihály Ruppert, Nabil V. Sayour, Viktória E. Tóth, Tamás Kovács, Zsombor I. Hegedűs, Zsófia Onódi, Alexandra Fábián, Attila Kovács, Tamás Radovits, Béla Merkely, Pál Pacher, Péter Ferdinandy, Zoltán V. Varga
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Is non-alcoholic fatty liver disease a sign of left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus? A systematic review and meta-analysis
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Seung Eun Lee, Juhwan Yoo, Bong-Seong Kim, Han Seok Choi, Kyungdo Han, Kyoung-Ah Kim
Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef
Metabolic Dysfunction-Associated Fatty Liver Disease and Mortality: A Population-Based Cohort Study
Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
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Jose Arriola-Montenegro, Renato Beas, Renato Cerna-Viacava, Andres Chaponan-Lavalle, Karla Hernandez Randich, Diego Chambergo-Michilot, Herson Flores Sanga, Pornthira Mutirangura
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Non-alcoholic Fatty Liver Disease and Its Association With Left Ventricular Diastolic Dysfunction: A Systematic Review
Namra V Gohil, Nida Tanveer, Vijaya Krishna Makkena, Arturo P Jaramillo, Babatope L Awosusi, Javaria Ayyub, Karan Nareshbhai Dabhi, Tuheen Sankar Nath
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Non-Alcoholic Fatty Liver Disease and Echocardiographic Parameters of Left Ventricular Diastolic Function: A Systematic Review and Meta-Analysis
Athina Goliopoulou, Panagiotis Theofilis, Evangelos Oikonomou, Artemis Anastasiou, Panteleimon Pantelidis, Maria Ioanna Gounaridi, Georgios E. Zakynthinos, Ourania Katsarou, Eva Kassi, Vaia Lambadiari, Dimitris Tousoulis, Manolis Vavuranakis, Gerasimos Si
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Rong Yang, Jian-Gao Fan
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Evangelos Cholongitas, Dimitrios Tsilingiris, Panagiota Diamantopoulou, Elpida Mastrogianni, Anastasios Tentolouris, Dimitrios Karagiannakis, Ioannis Moyssakis, George V. Papatheodoridis, Nikolaos Tentolouris
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Yu Dong, Guangsen Li
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Nengguang Fan, Xiaoying Ding, Qin Zhen, Liping Gu, Aifang Zhang, Tingting Shen, Yufan Wang, Yongde Peng
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Nonalcoholic fatty liver disease, diastolic dysfunction, and impaired myocardial glucose uptake in patients with type 2 diabetes
Minyoung Lee, Kwang Joon Kim, Tae‐Ha Chung, Jaehyun Bae, Yong‐ho Lee, Byung‐Wan Lee, Bong‐Soo Cha, Mijin Yun, Eun Seok Kang
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Mohammad Said Ramadan, Vincenzo Russo, Gerardo Nigro, Emanuele Durante-Mangoni, Rosa Zampino
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Correlation Between 25-Hydroxyvitamin D Level and Cardiac Diastolic Dysfunction in Chinese Adults with Early-Onset Type 2 Diabetes Mellitus: A Cross-Sectional Study
Lei Xiu, Xiao-ai Yao, Tao Jiang
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2021; Volume 14: 1823. CrossRef
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Guoxin Huang, Hui Zhou, Chao Shen, Yihui Sheng, Ruyu Xue, Chen Dong, Shaoyan Zhang
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Response: Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus (Diabetes Metab J 2020;44:267–76)
Hokyou Lee, Gyuri Kim, Yong-ho Lee
Diabetes & Metabolism Journal.2020; 44(3): 486. CrossRef
Letter: Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus (Diabetes Metab J2020;44:267–76)
Sung Hoon Yu
Diabetes & Metabolism Journal.2020; 44(3): 482. CrossRef

Complications
Color Doppler Ultrasonography Is a Useful Tool for Diagnosis of Peripheral Artery Disease in Type 2 Diabetes Mellitus Patients with Ankle-Brachial Index 0.91 to 1.40: Kyu Yeon Hur, Ji Eun Jun, Young Ju Choi, Yong-ho Lee, Dae Jung Kim, Seok Won Park, Byung Wook Huh, Eun Jig Lee, Sun-Ha Jee, Kap Bum Huh, Sung Hee Choi; Diabetes Metab J. 2018;42(1):63-73. Published online February 23, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.1.63

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Background

The clinical utility of ankle-brachial index (ABI) is not clear in subjects with less severe or calcified vessel. Therefore, we investigated the usefulness of color Doppler ultrasonography for diagnosing peripheral artery disease (PAD) in type 2 diabetes mellitus (T2DM) subjects.

Methods

We analyzed 324 T2DM patients who concurrently underwent ABI and carotid intima-media thickness (CIMT) measurements and color Doppler ultrasonography from 2003 to 2006. The degree of stenosis in patients with PAD was determined according to Jager's criteria, and PAD was defined as grade III (50% to 99% stenosis) or IV stenosis (100% stenosis) by color Doppler ultrasonography. Logistic regression analysis and receiver operating characteristic curve analysis were performed to evaluate the risk factors for PAD in patients with ABI 0.91 to 1.40.

Results

Among the 324 patients, 77 (23.8%) had ABI 0.91 to 1.40 but were diagnosed with PAD. Color Doppler ultrasonography demonstrated that suprapopliteal arterial stenosis, bilateral lesions, and multivessel involvement were less common in PAD patients with ABI 0.91 to 1.40 than in those with ABI ≤0.90. A multivariate logistic regression analysis demonstrated that older age, current smoking status, presence of leg symptoms, and high CIMT were significantly associated with the presence of PAD in patients with ABI 0.91 to 1.40 after adjusting for conventional risk factors. CIMT showed significant power in predicting the presence of PAD in patients with ABI 0.91 to 1.40.

Conclusion

Color Doppler ultrasonography is a useful tool for the detection of PAD in T2DM patients with ABI 0.91 to 1.40 but a high CIMT.

Citations

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Sherif M Zaki, Dina S El Karsh, Tuleen M Faden, Leen T Almghamsi, Joud O Fathaldin, Omar A Alhazmi
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Optimal Waist Circumference Cutoff Value Based on Insulin Resistance and Visceral Obesity in Koreans with Type 2 Diabetes: Jung Soo Lim, Young Ju Choi, Soo-Kyung Kim, Byoung Wook Huh, Eun Jig Lee, Kap Bum Huh; Diabetes Metab J. 2015;39(3):253-263. Published online April 24, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.3.253

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Abstract PDF Supplementary Material PubReader

Background

Visceral obesity is the most powerful contributor to the development of metabolic syndrome (MetS) and cardiovascular diseases. In light of visceral obesity, however, there is a paucity of data on the appropriate cutoff point of waist circumference (WC) in subjects with type 2 diabetes. The aim of this study was to investigate the optimal cutoff value for WC that signals insulin resistance (IR) and visceral obesity in Koreans with type 2 diabetes.

Methods

We evaluated 4,252 patients with type 2 diabetes (male 2,220, female 2,032, mean age 57.24 years) who visited our clinic between January 2003 and June 2009. WC was measured at the midpoint between the lower rib and the iliac crest, and insulin sensitivity was assessed by the rate constant of plasma glucose disappearance (Kitt %/min) using an insulin tolerance test. Visceral fat thickness was measured using ultrasonography. Statistical analysis was performed using receiver operating characteristic curve.

Results

The optimal cutoff points for WC for identifying the presence of IR and visceral obesity, as well as two or more metabolic components, were 87 cm for men and 81 cm for women. Moreover, these cutoff points had the highest predictive powers for the presence of visceral obesity. The MetS defined by new criteria correlated with the increased carotid intima-media thickness in female subjects.

Conclusion

Our results suggest that the optimal cutoff values for WC in Koreans with type 2 diabetes should be reestablished based on IR and visceral obesity.

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Brief Report

Beneficial Effects of Omega-3 Fatty Acids on Low Density Lipoprotein Particle Size in Patients with Type 2 Diabetes Already under Statin Therapy: Myung Won Lee, Jeong Kyung Park, Jae Won Hong, Kwang Joon Kim, Dong Yeob Shin, Chul Woo Ahn, Young Duk Song, Hong Keun Cho, Seok Won Park, Eun Jig Lee; Diabetes Metab J. 2013;37(3):207-211. Published online June 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.3.207

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Abstract PDF PubReader

Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C), additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (≥200 mg/dL) while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL) particle size and triglyceride (TG) level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%±3.1% vs. 2.3%±3.6%, P=0.024; -41.0%±24.1% vs. -24.2%±31.9%, P=0.049). Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects.

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Original Articles

In vivo Corneal Confocal Microscopy and Nerve Growth Factor in Diabetic Microvascular Complications.: Ji Sun Nam, Young Jae Cho, Tae Woong Noh, Chul Sik Kim, Jong Suk Park, Min ho Cho, Hai Jin Kim, Ji Eun Yoon, Han Young Jung, Eun Seok Kang, Yu Mie Rhee, Hyung Keun Lee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2007;31(4):351-361. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.351

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Abstract PDF: BACKGROUND
In vivo corneal confocal microscopy (IVCCM) is being recognized as a non-invasive, early diagnostic tool for diabetic neuropathy, for it provides a clear image of corneal subbasal nerve plexus in detail. Nerve growth factors (NGF) are believed to regulate peripheral and central nervous system, neuronal differentiation, and regeneration of damaged nerves, and their role in diabetic neuropathy is being emphasized these days. Moreover, NGFs and receptors are also expressed in retina and renal mesangial cells, suggesting their possible role in the common pathogenesis of diabetic microvascular complications. We plan to examine corneal structures of diabetic patients and compare IVCCM with conventional tools and analyze their serum and tear NGF levels. METHODS: IVCCM, nerve conduction velocity (NCV), and serum, urine, and tear samplings were done to 42 diabetic patients. From IVCCM, we measured corneal nerve density, branch, and tortuosity, total corneal/epithelial thickness, and the number of endothelial/keratocyte cells, and we checked patients' biochemical profiles and serum and tear NGF levels. RESULTS: Patients with more severe neuropathy had less corneal endothelial cells (3105 +/- 218 vs. 2537 +/- 142 vs. 2350 +/- 73/mm3 vs. 1914 +/- 465/mm3, P = 0.02), higher serum NGF (36 +/- 15 vs. 60 +/- 57.66 vs. 80 +/- 57.63 vs. 109 +/- 60.81 pg/mL, P = 0.39) and tear NGF levels (135.00 +/- 11.94 vs. 304.29 +/- 242.44 vs. 538.50 +/- 251.92 vs. 719.50 +/- 92.63 pg/mL, P = 0.01). There was a positive correlation between neuropathy and corneal nerve tortuosity (r2 = 0.479, P = 0.044) and negative correlation between neuropathy and endothelial cell count (r2 = -0.709, P = 0.002). Interestingly, similar changes were seen in other microvascular complications as well. CONCLUSION: Our results provide a possibility of using novel tools, IVCCM and NGF, as common diagnostic tools for diabetic microvascular complications, but it should be followed by a large population study.

Activation of NF-kappaB and AP-1 in Peripheral Blood Mononuclear Cells Isolated from Patients with Diabetic Nephropathy.: Jisun Nam, Min Ho Cho, Jong Suk Park, Geun Taek Lee, Hai Jin Kim, Eun Seok Kang, Yu Mie Lee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hun Joo Ha, Hyun Chul Lee; Korean Diabetes J. 2007;31(3):261-273. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.261

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Abstract PDF: BACKGROUND
We evaluated the role of oxidative stress in diabetic nephropathy by measuring intracellular reactive oxygen species (ROS) and redox-sensitive transcription factors in isolated peripheral mononuclear cells (PBMC). METHODS: From 66 diabetic patients with or without diabetic nephropathy (Group III and II, respectively) and 49 normal control subjects (Group I), spontaneous and stimulated ROS levels, activities of nuclear factor-kappa B (NF-kappaB), activator protein-1 (AP-1), and specificity protein1 (Sp1) in PBMC, urinary and PBMC TGF-beta1 (transforming growth factor-beta1), and 24-hour urinary albumin excretion (UAE) were measured. RESULTS: Spontaneous ROS was significantly higher in group III and II than group I (60.7 +/- 3.3 vs. 60.0 +/- 3.0 vs. 41.1 +/- 2.4%, respectively), and stimulated ROS were significantly higher in Group III compared to Group II (Increment of H2O2-induced ROS production: 21.8 +/- 2.2 vs. 11.1 +/- 2.0%, respectively; increment of PMA-induced ROS production 23.5 +/- 4.5 vs. 21.6 +/- 2.2%, respectively). The activities of NF-kappaB and AP-1, but not of Sp1, were significantly higher in Group III than in Group II (2.53 vs. 2.0 vs. 1.43-fold, respectively). Both PBMC- and urinary TGF-beta1 levels were higher in Group III than Group II (3.23 +/- 0.39 vs. 1.99 +/- 0.68 ng/mg in PBMCs, 16.88 +/- 6.84 vs. 5.61 +/- 1.57 ng/mL in urine, both respectively), and they were significantly correlated with activities of NF-kappaB and AP-1 and 24-hour UAE. CONCLUSIONS: Increased intracellular ROS generation in PBMCs of diabetic patients is involved in the pathogenesis of diabetic nephropathy through activation of NF-kappaB and AP-1, but not Sp1, and increased expression of TGF-beta1.

Thebeta3-adrenergic Receptor Gene Polymorphism in Non-Insulin Dependent Diabetes Mellitus.: Ji Hyun Lee, Hai Ri Li, Sang Won Lee, Su Youn Nam, Young Jun Won, Bong Soo Cha, Moon Suk Nam, Young Duk Song, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1997;21(2):130-137. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The B3-adrenergic receptor, located mainly in adipose tissue, is known to be involved in the regulation of lipolysis and thermogenesis. Recently studies have shown that the B3-adrenergic receptor gene polymorphism is associated with Non-Insulin Dependent Diabetes Mellitus(NIDDM) and insulin resistance. We investigated the relationship between the B3-adrenergic receptor gene polymorphism and the cli!ical and biochemical features of NIDDM patients. METHODS: Anthropometeric and biochemi al characteristics were determined for 134 NIDDM subjects and 30 nondiabetic controls. All subjects were genotyped for the 0-adrenergic receptor gene mutation using restriction fragment length polymorphism assay. RESULTS: The allelic frequency of the mutated allele was similar in NIDDM subjects and nondiabetic controls(11%, 12% respectively). There was no difference in the Arg64 allelic frequency of the B3-adrenergic receptor gene according to the onset age of diabetes. In diabetic group, the clinical and biochemical characteristics were not statistically different between the B3-adrenergic receptor gene mutation and nonmutation group. In control group, also no clinical differences were found between mutation and non-mutation group. When comparing frequency of obesity according to the B3-adrenergic receptor gene mutation in diabetic patients, we did not find the difference between the two groups. CONCLUSION: These results suggest that the b3-adrenergic receptor gene is not a major determinant for the development of obesity and NIDDM in Korea.

A case of insulinoma localized by endoscopic ultrasonography and intraoperative ultrasonography.: Jae Sik Cho, Kyeong Mi Lee, Eun Jig Lee, Kyung Rac Kim, Jae Bok Jng, Hyun Chul Le, Kap Bum Huh, Hee Dae Lee, Ki Hwang Kim, Ki Bum Lee; Korean Diabetes J. 1993;17(3):315-320. Published online January 1, 2001

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Abstract PDF: No abstract available.

The relationship between renin-aldosterone system and obesity in non-insulin dependent diabetes mellitus(NIDDM).: Kwang Jin Ahn, Yoon Sok Chung, Choon Hee Chung, Eun Jig Lee, Sung Kil Lim, Kyung Rac Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1993;17(3):283-291. Published online January 1, 2001

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Abstract PDF: No abstract available.

Effects of w3 fatty acid supplementation on serum lipids in patients with non-insulin dependent diabetes mellitus.: Yoon Sok Chung, Seog Won Park, Jin Ahn Kim, Eun Jig Lee, Sung Kil Lim, Kyung Rac Kim, Hyun Chul Lee, Kap Bum Huh, In Kyoung Paik, Ji Young Yoon, Hee Son Kim, Hyun Jong Chang; Korean Diabetes J. 1993;17(3):267-274. Published online January 1, 2001

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Abstract PDF: No abstract available.

Is the pancreas of cytomegalovirus genome in type I diabetic Koreans significant?.: Yoon Sok Chung, Hyun Chul Lee, Kwang Jin Ahn, Eun Jig Lee, Seung Kil Lim, Kap Bum Huh, Dong Soo Kim, Duk Hi Kim, Jeong Im Lee; Korean Diabetes J. 1991;15(2):213-219. Published online January 1, 2001

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Abstract PDF: No abstract available.

Insulin secretory capacity of human fetal pancreas.: Hyun Chul Lee, Kwang Jin Ahn, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Kap Bum Huh; Korean Diabetes J. 1991;15(2):197-203. Published online January 1, 2001

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Abstract PDF: No abstract available.

The effect of interleukin-1 beta on isolated rat pancreatic islets.: Hyun Chul Lee, Kwang Jin Ahn, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Kap Bum Huh; Korean Diabetes J. 1991;15(1):73-78. Published online January 1, 2001

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Abstract PDF: No abstract available.

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