Diabetes & Metabolism Journal

Original Articles

Clinical Diabetes & Therapeutics
Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks: Soo Lim, Kyoung Min Kim, Sin Gon Kim, Doo Man Kim, Jeong-Taek Woo, Choon Hee Chung, Kyung Soo Ko, Jeong Hyun Park, Yongsoo Park, Sang Jin Kim, Hak Chul Jang, Dong Seop Choi; Diabetes Metab J. 2017;41(5):377-385. Published online October 24, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.5.377

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Background

The aim of this multicenter, randomized, double-blind study was to examine the effect of lobeglitazone, a novel thiazolidinedione, on the changes in bone mineral density (BMD) in patients with type 2 diabetes mellitus.

Methods

A 24-week, double-blinded phase was followed by a 28-week, open-label phase, in which the placebo group also started to receive lobeglitazone. A total of 170 patients aged 34 to 76 years were randomly assigned in a 2:1 ratio to receive lobeglitazone 0.5 mg or a matching placebo orally, once daily. BMD was assessed using dual-energy X-ray absorptiometry at week 24 and at the end of the study (week 52).

Results

During the double-blinded phase, the femur neck BMD showed decreasing patterns in both groups, without statistical significance (−0.85%±0.36% and −0.78%±0.46% in the lobeglitazone and placebo groups, respectively). The treatment difference between the groups was 0.07%, which was also not statistically significant. Further, minimal, nonsignificant decreases were observed in both groups in the total hip BMD compared to values at baseline, and these differences also did not significantly differ between the groups. During the open-label phase, the BMD was further decreased, but not significantly, by −0.32% at the femur neck and by −0.60% at the total hip in the lobeglitazone group, and these changes did not significantly differ compared with the original placebo group switched to lobeglitazone.

Conclusion

Our results indicate that treatment with lobeglitazone 0.5 mg over 52 weeks showed no detrimental effect on the BMD compared to the placebo.

Citations

Citations to this article as recorded by

Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis
Deep Dutta, Saptarshi Bhattacharya, Manoj Kumar, Priyankar K. Datta, Ritin Mohindra, Meha Sharma
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102697. CrossRef
Efficacy and safety of lobeglitazone, a new Thiazolidinedione, as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis
Shashank R. Joshi, Saibal Das, Suja Xaviar, Shambo Samrat Samajdar, Indranil Saha, Sougata Sarkar, Shatavisa Mukherjee, Santanu Kumar Tripathi, Jyotirmoy Pal, Nandini Chatterjee
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102703. CrossRef
The benefits of adipocyte metabolism in bone health and regeneration
Lisa-Marie Burkhardt, Christian H. Bucher, Julia Löffler, Charlotte Rinne, Georg N. Duda, Sven Geissler, Tim J. Schulz, Katharina Schmidt-Bleek
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
Will lobeglitazone rival pioglitazone? A systematic review and critical appraisal
Kalyan Kumar Gangopadhyay, Awadhesh Kumar Singh
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(4): 102747. CrossRef
Comparison of therapeutic efficacy and safety of sitagliptin, dapagliflozin, or lobeglitazone adjunct therapy in patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea and metformin: Third agent study
Jun Hwa Hong, Jun Sung Moon, Kayeon Seong, Soo Lim
Diabetes Research and Clinical Practice.2023; 203: 110872. CrossRef
Bone Mineral Density Evaluation Among Type 2 Diabetic Patients in Rural Haryana, India: An Analytical Cross-Sectional Study
Nitish Khandelwal, Surbhi Rajauria, Siddhesh Pandurang Kanjalkar, Omkar Shivaji Chavanke, Sanjay Rai
Cureus.2023;[Epub] CrossRef
Lobeglitazone and Its Therapeutic Benefits: A Review
Balamurugan M, Sarumathy S, Robinson R
Cureus.2023;[Epub] CrossRef
A double‐blind, Randomized controlled trial on glucose‐lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase‐4 inhibitor therapy: REFIND study
Soree Ryang, Sang Soo Kim, Ji Cheol Bae, Ji Min Han, Su Kyoung Kwon, Young Il Kim, Il Seong Nam‐Goong, Eun Sook Kim, Mi‐kyung Kim, Chang Won Lee, Soyeon Yoo, Gwanpyo Koh, Min Jeong Kwon, Jeong Hyun Park, In Joo Kim
Diabetes, Obesity and Metabolism.2022; 24(9): 1800. CrossRef
A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus
Bo-Yeon Kim, Hyuk-Sang Kwon, Suk Kyeong Kim, Jung-Hyun Noh, Cheol-Young Park, Hyeong-Kyu Park, Kee-Ho Song, Jong Chul Won, Jae Myung Yu, Mi Young Lee, Jae Hyuk Lee, Soo Lim, Sung Wan Chun, In-Kyung Jeong, Choon Hee Chung, Seung Jin Han, Hee-Seok Kim, Ju-Y
Diabetes & Metabolism Journal.2022; 46(6): 855. CrossRef
Comparative Efficacy of Lobeglitazone Versus Pioglitazone on Albuminuria in Patients with Type 2 Diabetes Mellitus
Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
Diabetes Therapy.2021; 12(1): 171. CrossRef
Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus
Jaehyun Bae, Taegyun Park, Hyeyoung Kim, Minyoung Lee, Bong-Soo Cha
Diabetes & Metabolism Journal.2021; 45(3): 326. CrossRef
Effect of lobeglitazone on motor function in rat model of Parkinson’s disease with diabetes co-morbidity
Kambiz Hassanzadeh, Arman Rahimmi, Mohammad Raman Moloudi, Rita Maccarone, Massimo Corbo, Esmael Izadpanah, Marco Feligioni
Brain Research Bulletin.2021; 173: 184. CrossRef
Recent Perspective on Thiazolidinedione
Won Jun Kim
The Journal of Korean Diabetes.2021; 22(2): 97. CrossRef
Use of in vitro bone models to screen for altered bone metabolism, osteopathies, and fracture healing: challenges of complex models
Sabrina Ehnert, Helen Rinderknecht, Romina H. Aspera-Werz, Victor Häussling, Andreas K. Nussler
Archives of Toxicology.2020; 94(12): 3937. CrossRef
Update on: effects of anti-diabetic drugs on bone metabolism
Guillaume Mabilleau, Béatrice Bouvard
Expert Review of Endocrinology & Metabolism.2020; 15(6): 415. CrossRef
The use of metformin, insulin, sulphonylureas, and thiazolidinediones and the risk of fracture: Systematic review and meta‐analysis of observational studies
Khemayanto Hidayat, Xuan Du, Meng‐Jiao Wu, Bi‐Min Shi
Obesity Reviews.2019; 20(10): 1494. CrossRef
Diabetes pharmacotherapy and effects on the musculoskeletal system
Evangelia Kalaitzoglou, John L. Fowlkes, Iuliana Popescu, Kathryn M. Thrailkill
Diabetes/Metabolism Research and Reviews.2019;[Epub] CrossRef
Morin Exerts Anti‐Arthritic Effects by Attenuating Synovial Angiogenesis via Activation of Peroxisome Proliferator Activated Receptor‐γ
Mengfan Yue, Ni Zeng, Yufeng Xia, Zhifeng Wei, Yue Dai
Molecular Nutrition & Food Research.2018;[Epub] CrossRef
The effects of diabetes therapy on bone: A clinical perspective
Karim G. Kheniser, Carmen M. Polanco Santos, Sangeeta R. Kashyap
Journal of Diabetes and its Complications.2018; 32(7): 713. CrossRef
Changes in the Bone Mineral Density of Femur Neck and Total Hip Over a 52-Week Treatment with Lobeglitazone
Da Young Lee, Ji A Seo
Diabetes & Metabolism Journal.2017; 41(5): 374. CrossRef

Obesity and Metabolic Syndrome
The Usefulness of the Glycosylated Hemoglobin Level for the Diagnosis of Gestational Diabetes Mellitus in the Korean Population: Ah Jeong Ryu, Hyuk Jin Moon, Joo Ok Na, Yeo Joo Kim, Sang Jin Kim, Sang Il Mo, Jeong Ran Byun; Diabetes Metab J. 2015;39(6):507-511. Published online November 23, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.6.507

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Abstract PDF PubReader

Background

An oral glucose tolerance test (OGTT) is the current method used for screening and diagnosis of gestational diabetes mellitus (GDM). OGTT is a relatively complicated procedure and is expensive. Thus, new strategies that do not require fasting or more than a single blood draw may improve the diagnosis of GDM and increase the rate of GDM testing. We investigated the utility of monitoring glycosylated hemoglobin (HbA1c) levels for the diagnosis of GDM.

Methods

The data from 992 pregnant women with estimated gestational ages ranging from 24 to 28 weeks were retrospectively reviewed. There were 367 women with plasma glucose levels ≥140 mg/dL 1 hour after a 50-g OGTT. GDM was diagnosed according to the Carpenter-Coustan criteria for a 3-hour 100 g OGTT. A HbA1c assessment was performed at the same time.

Results

We enrolled 343 women in this study, and there were 109 women with GDM. The area under the curve the receiver operating characteristic curve for HbA1c detection of GDM was 0.852 (95% confidence interval, 0.808 to 0.897). A HbA1c cutoff value ≥5.35% had maximal points on the Youden index (0.581). The sensitivity was 87.2% and the specificity was 70.9% for diagnosing GDM. A threshold value ≥5.35% indicated that 163 patients had GDM and that 68 (41.7%) were false positive. The positive predictive value was 58.3% at this threshold value.

Conclusion

Despite substantial progress in methodology, HbA1c values cannot replace OGTT for the diagnosis of GDM.

Citations

Citations to this article as recorded by

Predelivery HbA1c levels and their relationship with adverse perinatal outcomes in women with normal 75-g OGTT
Xiaoxia Tang, Jin Wei, Zifeng Jiang, Shaohua Wu
Archives of Gynecology and Obstetrics.2023;[Epub] CrossRef
The diagnostic value of glycosylated hemoglobin for gestational diabetes mellitus in Asian populations: A systematic review and meta‐analysis
Jiani Zhang, Fan Zhou, Tingting Xu, Jinfeng Xu, Yaqian Li, Li Lin, Qi Cao, Xiaodong Wang
Journal of Obstetrics and Gynaecology Research.2022; 48(4): 902. CrossRef
The role of first-trimester HbA1c in the early detection of gestational diabetes
Mehrnaz Valadan, Zeinab Bahramnezhad, Fatemeh Golshahi, Elham Feizabad
BMC Pregnancy and Childbirth.2022;[Epub] CrossRef
Glycaemic Variability and Risk Factors of Pregnant Women with and without Gestational Diabetes Mellitus Measured by Continuous Glucose Monitoring
Martina Gáborová, Viera Doničová, Ivana Bačová, Mária Pallayová, Martin Bona, Igor Peregrim, Soňa Grešová, Judita Štimmelová, Barbora Dzugasová, Lenka Šalamonová Blichová, Viliam Donič
International Journal of Environmental Research and Public Health.2021; 18(7): 3402. CrossRef
A Review on Research Progress in the Application of Glycosylated Hemoglobin and Glycated Albumin in the Screening and Monitoring of Gestational Diabetes
Xinyan Liu, Na Wu, Abdulrahman Al-Mureish
International Journal of General Medicine.2021; Volume 14: 1155. CrossRef
Evaluation of the Combination of HbA1C with Hematocrit for Early Screening of Gestational Diabetes Mellitus
Ali Reza Norouzi, Mahsa Siavashi, Fatemeh Norouzi, Maryam Talayeh, Somayyeh Noei Teymoordash
Journal of Obstetrics, Gynecology and Cancer Research.2021; 6(4): 217. CrossRef
The accuracy of haemoglobin A1c as a screening and diagnostic test for gestational diabetes: a systematic review and meta-analysis of test accuracy studies
Chiamaka Esther Amaefule, Archana Sasitharan, Princee Kalra, Stamatina Iliodromoti, Mohammed S.B. Huda, Ewelina Rogozinska, Javier Zamora, Shakila Thangaratinam
Current Opinion in Obstetrics & Gynecology.2020; 32(5): 322. CrossRef
Downregulation of microRNA-873 attenuates insulin resistance and myocardial injury in rats with gestational diabetes mellitus by upregulating IGFBP2
Na Han, Hai-Yan Fang, Jie-Xuan Jiang, Qian Xu
American Journal of Physiology-Endocrinology and Metabolism.2020; 318(5): E723. CrossRef
Reliability of glycosylated hemoglobin in the diagnosis of gestational diabetes mellitus
Duria A. Rayis, Abdel B. A. Ahmed, Manal E. Sharif, Amir ElSouli, Ishag Adam
Journal of Clinical Laboratory Analysis.2020;[Epub] CrossRef
Mid‐trimester glycosylated hemoglobin levels (HbA1c) and its correlation with oral glucose tolerance test (World Health Organization 1999)
Devanshi Dubey, Shipra Kunwar, Uma Gupta
Journal of Obstetrics and Gynaecology Research.2019; 45(4): 817. CrossRef
The utility of HbA1c combined with haematocrit for early screening of gestational diabetes mellitus
Kui Wu, Yan Cheng, Tingting Li, Ziwen Ma, Junxiu Liu, Qingying Zhang, Haidong Cheng
Diabetology & Metabolic Syndrome.2018;[Epub] CrossRef
The Cutoff Value of HbA1c in Predicting Diabetes and Impaired Fasting Glucose
Seyoung Kwon, Youngak Na
The Korean Journal of Clinical Laboratory Science.2017; 49(2): 114. CrossRef
Diagnosing gestational diabetes mellitus: implications of recent changes in diagnostic criteria and role of glycated haemoglobin (HbA1c)
Fahmy W Hanna, Christopher J Duff, Ann Shelley-Hitchen, Ellen Hodgson, Anthony A Fryer
Clinical Medicine.2017; 17(2): 108. CrossRef
Utility of Glycated Haemoglobin in Gestational Diabetes Mellitus: Present and Future
Rajesh Rajput, Deepak Jain
EMJ Diabetes.2016; : 84. CrossRef

The Effect of Tribbles-Related Protein 3 on ER Stress-Suppressed Insulin Gene Expression in INS-1 Cells: Young Yun Jang, Nam Keong Kim, Mi Kyung Kim, Ho Young Lee, Sang Jin Kim, Hye Soon Kim, Hye-Young Seo, In Kyu Lee, Keun Gyu Park; Korean Diabetes J. 2010;34(5):312-319. Published online October 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.5.312

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Abstract PDF PubReader

Background

The highly developed endoplasmic reticulum (ER) structure in pancreatic beta cells is heavily involved in insulin biosynthesis. Thus, any perturbation in ER function inevitably impacts insulin biosynthesis. Recent studies showed that the expression of tribbles-related protein 3 (TRB3), a mammalian homolog of Drosophilia tribbles, in various cell types is induced by ER stress. Here, we examined whether ER stress induces TRB3 expression in INS-1 cells and found that TRB3 mediates ER stress-induced suppression of insulin gene expression.

Methods

The effects of tunicamycin and thapsigargin on insulin and TRB3 expression in INS-1 cells were measured by Northern and Western blot analysis, respectively. The effects of adenovirus-mediated overexpression of TRB3 on insulin, PDX-1 and MafA gene expression in INS-1 cells were measured by Northern blot analysis. The effect of TRB3 on insulin promoter was measured by transient transfection study with constructs of human insulin promoter.

Results

The treatment of INS-1 cells with tunicamycin and thapsigargin decreased insulin mRNA expression, but increased TRB3 protein expression. Adenovirus-mediated overexpression of TRB3 decreased insulin gene expression in a dose-dependent manner. A transient transfection study showed that TRB3 inhibited insulin promoter activity, suggesting that TRB3 inhibited insulin gene expression at transcriptional level. Adenovirus-mediated overexpression of TRB3 also decreased PDX-1 mRNA expression, but did not influence MafA mRNA expression.

Conclusions

This study showed that ER stress induced TRB3 expression, but decreased both insulin and PDX-1 gene expression in INS-1 cells. Our data suggest that TRB3 plays an important role in ER stress-induced beta cell dysfunction.

Citations

Citations to this article as recorded by

Endoplasmic reticulum stress causes insulin resistance by inhibiting delivery of newly synthesized insulin receptors to the cell surface
Max Brown, Samantha Dainty, Natalie Strudwick, Adina D. Mihai, Jamie N. Watson, Robina Dendooven, Adrienne W. Paton, James C. Paton, Martin Schröder, James Arthur Olzmann
Molecular Biology of the Cell.2020; 31(23): 2597. CrossRef
PTB and TIAR binding to insulin mRNA 3′- and 5′UTRs; implications for insulin biosynthesis and messenger stability
Rikard G. Fred, Syrina Mehrabi, Christopher M. Adams, Nils Welsh
Heliyon.2016; 2(9): e00159. CrossRef
Asna1/TRC40 Controls β-Cell Function and Endoplasmic Reticulum Homeostasis by Ensuring Retrograde Transport
Stefan Norlin, Vishal S. Parekh, Peter Naredi, Helena Edlund
Diabetes.2016; 65(1): 110. CrossRef
Role of the Unfolded Protein Response inβCell Compensation and Failure during Diabetes
Nabil Rabhi, Elisabet Salas, Philippe Froguel, Jean-Sébastien Annicotte
Journal of Diabetes Research.2014; 2014: 1. CrossRef
Endoplasmic Reticulum Stress and Insulin Biosynthesis: A Review
Mi-Kyung Kim, Hye-Soon Kim, In-Kyu Lee, Keun-Gyu Park
Experimental Diabetes Research.2012; 2012: 1. CrossRef

Case Reports

A Case of Multifocal Pyomyositis in Diabetes Mellitus.: Eun Seo Park, Joo Hyun Kim, Bo Yong Jung, Jae Ho Park, Ji Hun Ahn, Jun Young Lee, Soon Ho Hwang, Kyung Wook Lee, Jong Kyu Han, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo; Korean Diabetes J. 2006;30(2):140-144. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.140

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Abstract PDF: Pyomyositis is an acute bacterial infection of skeletal muscle, usually caused by Staphylococcus aureus. It is common in the tropics but rare in temperate climates. In temperature climate there are predisposing factors, such as diabetes, HIV infection, malignancy. The incidence of reported bacterial pyomyositis is increasing in recently, especially among immunocompromised persons such as HIV infection or diabetes mellitus. We experience multifocal pyomyositis in 49-year-old man with type 2 diabetes mellitus presented with drowsy mental state. Muscular USG and MRI finding shows multifocal abscess in thigh. Blood culture revealed Staphyloccus aureus. And patient received a intravenous broad-spectrum antibiotics, incision and drainage. He was successfully managed with drainage and antibiotics then discharge. Since diabetes or infection with HIV predisposes patients to bacterial infection, pyomyositis will occur more frequently. Increased awareness if the disease will improve management.

A Case of Acute Multifocal Bacterial Nephritis Associated with Diabetic Autonomic Neuropathy.: Eun Kyung Park, Jae Hak Lee, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo; Korean Diabetes J. 2003;27(4):379-384. Published online August 1, 2003

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Abstract PDF: Acute multifocal bacterial nephritis is a severe form of acute renal infection in which a heavy leukocytic infiltrate occurs throughout the kidney. It is also an early phase of renal corticomedullary abscess. Clinically, patients have evidence of a severe urinary tract infection secondary to a gram-negative organism and there are frequently signs of sepsis. About half of the reported patients have been diabetics. Urinary tract infections are more common in diabetic women than in non-diabetic women. A variety of factors may contribute. The most important predisposing factor may be bladder dysfunction as a result of diabetic neuropathy and cystopathy. Diabetic cystopathy begins as decreased bladder sensation and decreased reflex detrusor activity caused by neuropathy affecting sympathetic and parasympathetic afferent fibers. Impaired bladder sensation results in bladder distention and increased residual urine volume. Long-term effects may eventually be vesicoureteral reflux and recurrent upper urinary tract infection. However, until now no diabetic patient with acute multifocal bacterial nephritis has been reported in Korea. Acute multifocal bacterial nephritis can be diagnosed by clinical manifestations and on radiologic grounds, including abdominal computed tomography showing multiple, wedge shaped, poorly defined areas of decreased contrast enhancement in multiple renal lobes. Therefore, we report the first Korean case of acute multifocal bacterial nephritis associated with diabetic autonomic neuropathy and review the literatures.

A Case of Invasive Aspergillosis of the Nasal Septum in a Patient with Diabetes Mellitus.: Tae Hoon Kim, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo, Jang Mook Kim, Yoon Jung Kim; Korean Diabetes J. 2003;27(4):373-378. Published online August 1, 2003

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Abstract PDF: Invasive aspergillosis of the nasal cavity and paranasal sinuses is characterized by invasion and destruction of the bony sinus walls, the orbit, and other soft tissues of the face. It occurs particularly in patients with severe immune deficits, and less frequently in patients with diabetes mellitus. The therapeutic outcome of invasive aspergillosis is unsatisfactory. Mortality rates range from 50 to 80%, depending primarily on the underlying disease. In general, the prognosis depends on making a prompt diagnosis of infection and providing early treatment. However the diagnosis of invasive aspergillosis is difficult because there is no specific symptom, nor any rapid diagnostic method for confirmation. We report a case of a 64-year old woman with diabetes mellitus and invasive aspergillosis of the nasal septum. She was diagnosed by biopsy of the nasal septum and treated with systemic antifungal agent and surgical debridement. (Ed- paragraphs combined here) In conjunction with this case we review the previous literatures and suggest that prompt antifungal therapy with glycemic control is an important element in the treatment of invasive aspergillosis in a diabetic patient.

A Case of Endogenous Endophthalmitis in a Patient with Diabetic Retinopathy.: Chang Hee Han, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo, Jun Sun Kim; Korean Diabetes J. 2003;27(4):367-372. Published online August 1, 2003

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Abstract PDF: Infectious endogenous endophthalmitis can occur by entrance of a pathogenic microorganism into the eye from various primary infection sites other than the eye. Although relatively rare, it results in visual loss frequently in spite of early diagnosis and treatment. It occurs in the process of systemic infection and its underlying conditions are diabetes, advanced liver disease, and immune suppressive state or drug abuse. We report a case of a 51-year old man with proliferative diabetic retinopathy and endogenous endophthalmitis caused by S. aureus from a skin infection. The ocular symptoms improved after systemic and intravitreal antibiotic therapy but visual loss could not be prevented. In conjunction with this case, we review the available literatures and stress the seriousness of this disease when concurrent in diabetic patients.

Original Articles

The Prevalence of Islet Cell Cytoplasmic Antibody in Korean Type 1 Diabetes: Possible Replacement with Combined Measurement of Anti-GAD, Anti-ICA512, and Anti-phogrin Antibodies.: Kyoung Ah Kim, Dong Jun Kim, Jae Hoon Chung, Yong Ki Min, Moon Kyu Lee, Kwang Won Kim, Dong Kyu Jin, Kyung Soo Ko, Sang Jin Kim, Myung Shik Lee; Korean Diabetes J. 2001;25(6):430-445. Published online December 1, 2001

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Abstract PDF: BACKGROUND
Type 1 diabetes includes all forms of autoimmune-mediated and idiopathic beta-cell destruction leading to an absolute insulin deficiency. Evidence of an autoimmune pathogenesis was assessed by studying cytoplasmic islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), antibodies reacting with an islet tyrosine phosphatase-related molecule referred to as ICA512 (ICA512A), or its homologue phogrin (phogrin-A). In comparison with ICA, the best validation to assess the risk of type 1 diabetes, shows that a combination of antibodies to GADA with ICA512A has the power to detect a majority of ICA and 97~100% of subjects who progressed to overt diabetes. These findings suggest the possibility of replacing the laborious ICA test in the screening programs to identify subjects at risk of progressing to type 1 diabetes or forclassifying the stage of diabetes at the time of diagnosis. Up to now, it is unclear whether these results are applicable to the slowly progressive type 1 diabetes that appears to be more prevalent in Asian than in western countries. The prevalence of combined autoantibody testing (1 of GADA, ICA512A, or phogrin-A) was investigated in the patients with type 1 diabetes (typical and slowly progressive) and type 2 diabetes, and compared with that of ICA which is a more laborious and insensitive test. METHODS: The ICA assay was performed using immunoenzymatic staining of frozen human (blood group O) pancreatic sections with serial dilutions of serum samples with peroxidase-labeled protein A. For the GADA determination, commercially available GADA radioimmunoassay kits utilizing the 125I-labeled recombinant GAD65 (RSR , United Kingdom) as an antigen was used. Either ICA512A or phogrin-A were detected by a radioligand-binding assay after in vitro transcription and translation using the clone ICA512bdc or phogrin cDNA. Serum was obtainedfrom 76 patients with type 1 diabetes (mean age 22.8+/-14.0 years), 22 patients with slowly progressive type 1 diabetes (mean age 37.9+/-13.9 years) and 39 patients with type 2 diabetes (mean age 45.3+/-12.3 years). Typical and slowly progressive type 1 diabetes patients had the disease for between 4.0+/-4.6 and 10.1+/-9.5 years, respectively at the earliest serum sampling. RESULTS: 1) In typical type 1 diabetes, 30% of patients tested positive for ICA and 57% for the combined autoantibody test (1 of GADA, ICA512A, or phogrin-A). In the slowly progressive type 1 diabetes group, 18% of patients tested positive for ICA and 50% for the combined autoantibody test. In type 2 diabetes, 7.7% and 5.1% tested positive, respectively. 2) Ninety-six percent of ICA-positive patients expressed one or more of the 3 auto-antibody specificities in typical type 1 diabetes. Among the 53 ICA-negative patients with typical type 1 diabetes, 40% had one or more of these auto-antibodies. In the slowly progressive type 1 diabetes, 100% of the ICA-positive and 39% of the ICA- negative patients expressed one or more of the 3 autoantibody specificities. 3) Of the 23 patients with ICA-positive typical type 1 diabetes patients, 87% had a positive result for GADA, 48% for ICA512A, 44% for phogrin-A, and 96% for GADA or ICA512A. Of the 4 patients with ICA-positive slowly progressive type 1 diabetes, three had a positive result for GADA, and 1 for ICA512A. 4) When the prevalence of combined autoantibody testing was analyzed according to the duration of diabetes, the prevalence in patients tested within 4 years after the diagnosis and more than 4 years after the diagnosis was 61% and 52%, respectively in typical type 1 diabetes. Furthermore, that for the ICA was 37% and 21%, respectively. In the slowly progressive type 1 diabetes, the prevalence of combined auto-antibody testing was 88% and 25%, respectively (p<0.05), while that of ICA was 25% and 13%, respectively. 5) In typical type 1 diabetes, ICA were detected more frequently in patients younger than 15 years of age (48%) than in older patients (23%) (p<0.05), while the prevalence of combined auto-antibody testing -was not different according to the onset age (65% vs 53%). CONCLUSION: Combined autoantibody testing for GADA and ICA512A is more sensitive that ICA in type 1 diabetes. Therefore, it could replace the laborious ICA measurement and may be useful for discriminating the etiology of adult onset atypical diabetes.

The Relation Between DHEA, DHEAS and Syndrome X, Cardiovascular Complication in Type 2 Diabetes Mellitus.: Yong Hyun Kim, Jeong Heon Oh, Nan Hee Kim, Kyung Mook Choi, Sang Jin Kim, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2000;24(2):234-244. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Insulin is known as a major factor that regulates secretion of DHEA and DHEAS. Numerous studies are exist to investigate the relationship between DHEA(S) and insulin resistance. Furthermore, numerous previous studies revealed that insulin resistance plays a major role in the pathogenic relationship between DHEA(S) and type 2 diabetes mellitus. However, number of studies to investigate the difference of levels of DHEA(S) according to the presence of syndrome X in type 2 diabetes mellitus are limited. METHODS: In type 2 diabetes, aged from 40 to 70 years old, the levels of serum DHEA and DHEAS was compared between the subejcts with or without syndrome X as well as the normal age and sex matched control. Furthermore, correlation between serum DHEA/DHEAS and insulin resistance, and the levels of DHEA/DHEAS according to the cardiovascular complication status was also evaluated. RESULTS: 1. No statistical difference in serum DHEA and DHEAS was observed among the 3 groups. However, the serum DHEA and DHEAS levels were lower in type 2 diabetes with syndrome X and higher in normal control. 2. No correlation was observed between DHEA, DHEAS and insulin resistance factors. 3. No stastistical difference in serum DHEA and DHEAS was observed in type 2 diabetic patients with cardiovascular complications. However, the level of DHEA was lower in the patients with cardiovascular complications. 4. No stastistical difference in serum DHEA and DHEAS was observed according to the presence of cardiovascular complications when analysis was performed in 55 years and younger subjects. 5. The level of DHEA was lower in the presence of cardiovascular complication when only male diabetic subjects were included in the analysis, but the level of DHEAS showed no difference according to the cardiovascular complication status. CONCLUSION: No statistical difference of the levels of serum OHEA and DHEAS was observed according to the presence of syndrome X in type 2 diabetes patients, However, the level of serum DHEA tended to be lower in the presence of cardiovascular complications. The levels of DHEA in male diabetic subjects were lower in the presence of cardiovascular complication, thus, we suspected that DHEA may play a potential role as one of risk factors of cardiovascular complications in this subgroup.

Effects of Insulin and Vitamin E on the Apoptosis of Pancreatic Islet Cells in Multiple Low dose Streptozotocin Induced Diabetic (LDSD) Mice.: Yong Hyun Kim, Jeong Hun Oh, Nan Hee Kim, Kyung Muk Choi, Sang Jin Kim, Sei Hyun Baik, Eung Seok Lee, Min Chul Lee, Dong Seop Choi; Korean Diabetes J. 1999;23(6):757-767. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 1 diabetes mellitus results from irreversible loss of beta cells in pancreatic islet. It is generally known that abnormal MHC expression and interaction of variable cytokines play a role in beta cell death, but the precise mechanism of beta cell death is unknown. Apoptosis is a physiological form of cell death and can play an important role in beta cell death in experimental diabetic animal models. Thus, in insulin and vitamin E treated LDSD mice and streptozotocin treated control mice. We attempted to comparing the levels of blood glucose (BG), the degree of insulitis, and number of apoptotic cells. Our study goal was to understand inhibition of apoptosis which thought to play an important mechanism in reducing the degree of hyperglycemia and insulitis. METHODS: In 3 LDSD mice groups (group 1: control group with streptozotocin only, group 2: streptozotocin plus insulin, group 3: streptozotocin plus vitamin E), the effects of insulin and vitamin E on the blood glucose levels and the degree of insulitis were evaluated. The number of apoptotic cells of pancreatic islet was compared using double staining immunohistochemical method. RESULT: The levels of BG, degree of insulitis and the rate of apoptosis of pancreatic islet cells were decreased in insulin and vitamin E treated groups when compared to the control group. There was no difference in number of apoptotic cells between insulin and vitamin E treated group, but levels of BG and degree of insulitis were higher in vitamin E treated group than insulin treated group as time elapsed. CONCLUSION: Insulin and vitamin E can decrease the elevation of BG and the degree of insulitis via inhibition of apoptosis in LDSD mice.

Case Report

A Case of Severe Hypertriglyceridemia with Diabetic Ketoacidosis.: Dong Seop Choi, Jeong Heon Oh, Ie Byung Park, Jin Won Kim, Kyung Mook Choi, Yong Hyun Kim, Nan Hee Kim, Sang Jin Kim, Sei Hyun Baik; Korean Diabetes J. 1999;23(5):715-721. Published online January 1, 2001

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Abstract PDF: Severe hypertriglyceridemia exceeding 5.6 mmol/L in diabetic ketoacidosis occasionally occur in patients with type 1 diabetes mellitus. The pattern of dyslipidemia is usually Fredrickson classification type lV. But it also exists in type III and type V. However, extreme triglyceridemia, triglyceride level exceeds 22.6 mmol/L, occur rarely in the modern era of insulin therapy. And the pattern is usually Fredrickson type I. The severe hypertriglyceridemia in diabetic ketoacidosis is mainly due to lipoprotein lipase deficiency, and secondly to insulin deficiency. The severity usually improves with insulin replacement. In patients with extreme hypertriglyceri-demia, serum electrolyte values of the patients are fallaciously low, and it leads to the misinterpretation of biochemical results and to the inappropriate treatment. We reported a case of a 25 years old female patient with diabetic ketoacidosis and extreme hypertriglyceridemia. At admission, the color of her serum was milky, her plasma triglyceride concentration was 144.7 mmol/L (12864 mg/dL), cholesterol was 25.5 mmol/L (982 mg/dl), and HDL-cholesterol was 0.77 mmol/L (40 mg/dL). The biochemical values at admission could not be measured. Empirical therapy was administered with the use of insulin and fluid. After the initial treatment with insulin and fluid, plasma triglyceride declined rapidly and was nearly normal after 72 hours. We also measured fasting blood glucose concentration and lipid profiles from her father and two sisters. Their plasma glucose and lipid profiles were normal.

Original Articles

Serum Levels of Sialic acid, CRP, and TNF-a in Type 2 Diabetin Patients with Syndrome X.: Dong Seop Choi, Sang Jin Kim, Se Hyeon Paek, Kyung Mook Choi, Nan Hee Kim, Jung Heon Oh, Young Hyun Kim; Korean Diabetes J. 1999;23(3):307-314. Published online January 1, 2001

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Abstract PDF: diabetic nephropathy and macro- vascular complications. Thus it is possible to conBACKGROUND: Type 2 diabetes is associated with increased blood concentrations of acute phase reactants including; sialic acid, ai-acid glycoprotein, serum amyloid A, and the main cytokine mediator of acute phase response, interleukin-6. Through the action of cytokines on many tissues, acute phase response could be a major contributor of biochemical and clinical features of metabolic syndrome X and type 2 DM. We investigated whether sialic acid, CRP, and TNF-a levels were elevated in type 2 diabetic patients who had features of syndrome X and whether they were correlated with diabetic vascular complications. METHODS: Group 1 was type 2 diabetic patients with any of 4 or 5 features of syndrome X (n=24). Group 2 was type 2 diabetic patients with 0 or 1 features of syndrome X (n=29), and group 3 was healthy nondiabetic control subjects (n=19). We compared the levels of sialic acid, CRP, and TNF-a in group 1, 2 and 3. We also observed the relationship between sialic acid, CRP, TNF-a levels and diabetic micro, macrovascular complications and studied the correlation between these markers and components of syndrome X. RESULTS: Group 1 had significantly higher sialic acid levels than group 2 (68.3+19 vs. 59.9+9.7 mg/dL, p=0.047). But the CRP, and TNF-a levels were similar in three groups. Serum sialic acid levels were signifieantly higher in proteinuria group than in normo- and microalbuminuria groups (81+27.6 vs. 59.9+7.1, 61.2+7.9 mg/dL, p=0.001, 0.005). Serum CRP levels were also higher in proteinuria groups (32.9+59.8 vs. 6.4+1.9, 6.0+3.1mg/L, p=0.017, p=0.037). Serum sialic acid levels were significantly higher in the macrovascular complication group (70.5 +21.3 vs. 60.5+ 6.8 mg/dL, p=0.015). Levels of sialic acid were correlated with urinary albumin excretion rate, log triglyceride, CRP, and fasting C-peptide. Levels of CRP were correlated with sialic acid and fasting C-peptide. CONCLUSION: Serum sialic acid levels were significantly elevated in type 2 diabetic patients who had features of syndrome X, and were also elevated in patients with sider that the mechanisms involved in the acute phase response can contribute to the pathophysiology of type 2 diabetes and syndrome X. Vascular complications do further increase stress reactions in type 2 diabetes.

Serum Levels of Transforming Growth Factor ( TGF ) -beta1 in Type 2 Diabetic Patients.: Nan Hee Kim, Jung Heon Oh, Young Hyun Kim, Ie Byung Park, Sang Jin Kim, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 1998;22(4):522-530. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Transforming growth factor(TGF)-Bl is a potent inducer of extracellular matrix production and of fibrogenesis and has been associated wnh the occurrence of diabetic complications. Our aim was to determine whether circulating levels of TGF-gl are altered in type 2 DM and, if so, whether they are correlated with blorxi glucose levels and show an association with diabetic complications. METHOD: Serum levels of TGF-gl were measured by quantitative sandwitch enzyme immunoassay in 76 type 2 DM patients and were correlated with clinical and biochemical parameters and the presence of diabetic complications. Result: 1) Serum TGF-B1 levels were correlated with fasting blood glucose levels (r=0.30, p=0.007) and inversely correlated with duration of diabetes (r=-0.31, p=0.007), BUN (r=-0.31, p=0.034), and creatinine (r=-0.40, p=0.004). In linear logistic regression analysis, duration of diabetes and HbA 1C <- were independently related to serum TGF-B1 levels. 2) Serum levels of TGF-B1 were significantly decreased in proteinuria group (n=23) than in normoalbuminuria group (n=26) (69.5+27.5 vs 85.7 +23 ng/mL, p=0.022). TGF-B1 concentrations were inversely correlated with serum creatinine and age in normoalbuminuria group (r=-0.40, p

A Case of Fibrocalculous Pancreatic Diabetes With Familial Tendency.: Chang In Kim, Myung In Lee, Dae Jun Lee, So Hee Son, Sook Hee Keun, Sang Jin Kim; Korean Diabetes J. 1998;22(1):103-109. Published online January 1, 2001

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Abstract PDF: Diabetes in tropical regions and in some developing countries presents clinically differently from IDDM and NIDDM in the Western world and developed countries. So, the WHO recognized malnutrition-related diabetes mellitus and subdivided into fibrcalculous pancreatic diabetes(FCPD) and protein-deficient pancreatic diabetes in 1995. While it appears that malnutrition may influence the expression of other types of diabetes, the evidence that diabetes can be directly caused by malnutrition is not convincing. Thus, at present time, FCPD is best considered as a secondary form of diabetes. FCPD is a form of diabetes with a high prevalence in tropical and developing countries, but rare in Korea. It occurrs in young indi.viduals, accompanied by pancreatic calculi and or ductal dilatation of unknown cause, and is ketosis-resistant. We experienced a case of FCPD with familial tendency and report with a brief review of the literature.

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