Diabetes & Metabolism Journal

Original Articles

Maternal and Neonatal Outcomes in Korean Women with Type 1 and Type 2 Diabetes: Hee-Sook Kim, Hye-Jung Jang, Jeong-Eun Park, Moon-Young Kim, Sun-Young Ko, Sung-Hoon Kim; Diabetes Metab J. 2015;39(4):316-320. Published online August 17, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.4.316

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Background

The purpose of this study was to evaluate maternal and neonatal outcomes in Korean women with type 1 diabetes and type 2 diabetes.

Methods

We performed a retrospective survey of 163 pregnancies in women with type 1 diabetes (n=13) and type 2 diabetes (n=150) treated from 2003 to 2010 at Cheil General Hospital & Women's Healthcare Center, Korea. We compared maternal characteristics as well as maternal and neonatal outcomes between groups.

Results

Differences in glycosylated hemoglobin between type 1 and type 2 diabetes were not significant. Birth weight (3,501±689.6 g vs. 3,366±531.4 g) and rate of major congenital malformations (7.7% vs. 5.6%) were not significantly different. However, women with type 1 diabetes had higher rates of preeclampsia (38.5% vs. 8.2%, P=0.006), large for gestational age (LGA; 46.2% vs. 20.4%, P=0.004), macrosomia (38.5% vs. 13.4%, P=0.032), and admission for neonatal care (41.7% vs. 14.8%, P=0.03) than women with type 2 diabetes.

Conclusion

Maternal and neonatal outcomes for women with type 1 diabetes were poorer than for women with type 2 diabetes, especially preeclampsia, LGA, macrosomia and admission to the neonatal intensive care unit.

Citations

Citations to this article as recorded by

The Impact of Type 2 Diabetes on Women’s Health and Well-being During Their Reproductive Years: A Mixed-methods Systematic Review
Aycan Celik, Rita Forde, Simona Racaru, Angus Forbes, Jackie Sturt
Current Diabetes Reviews.2022;[Epub] CrossRef
Application of the electronic nose in predicting preeclampsia in high-risk pregnancies. Pilot study
Karen Beatriz Méndez Rodríguez, Luis Manuel Ramírez Gómez, Leticia Carrizales Yáñez, Rogelio Flores Ramírez, Omar Ornelas-Rebolledo, Jaime Antonio Borjas-García, Francisco Pérez-Vázquez, Maribel Rodríguez Aguilar
Archives of Medical Research.2021;[Epub] CrossRef
Obstetric and neonatal complications among women with autoimmune disease
Andrew Williams, Katherine Grantz, Indulaxmi Seeni, Candace Robledo, Shanshan Li, Marion Ouidir, Carrie Nobles, Pauline Mendola
Journal of Autoimmunity.2019; 103: 102287. CrossRef
Effects of maternal age, parity and pre-pregnancy body mass index on the glucose challenge test and gestational diabetes mellitus
Adel T. Abu-Heija, Majeda R. Al-Bash, Moza A. Al-Kalbani
Journal of Taibah University Medical Sciences.2017; 12(4): 338. CrossRef
Deficient Vitamin E Uptake During Development Impairs Neural Tube Closure in Mice Lacking Lipoprotein Receptor SR-BI
Nicolás Santander, Carlos Lizama, María José Parga, Alonso Quiroz, Druso Pérez, Guadalupe Echeverría, Lorena Ulloa, Verónica Palma, Attilio Rigotti, Dolores Busso
Scientific Reports.2017;[Epub] CrossRef

1,5-Anhydroglucitol as a Useful Marker for Assessing Short-Term Glycemic Excursions in Type 1 Diabetes: Hannah Seok, Ji Hye Huh, Hyun Min Kim, Byung-Wan Lee, Eun Seok Kang, Hyun Chul Lee, Bong Soo Cha; Diabetes Metab J. 2015;39(2):164-170. Published online March 9, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.2.164

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Abstract PDF PubReader

Background

Type 1 diabetes is associated with more severe glycemic variability and more frequent hypoglycemia than type 2 diabetes. Glycemic variability is associated with poor glycemic control and diabetic complications. In this study, we demonstrate the clinical usefulness of serum 1,5-anhydroglucitol (1,5-AG) for assessing changes in glycemic excursion in type 1 diabetes.

Methods

Seventeen patients with type 1 diabetes were enrolled in this study. A continuous glucose monitoring system (CGMS) was applied twice at a 2-week interval to evaluate changes in glycemic variability. The changes in serum glycemic assays, including 1,5-AG, glycated albumin and hemoglobin A1c (HbA1c), were also evaluated.

Results

Most subjects showed severe glycemic excursions, including hypoglycemia and hyperglycemia. The change in 1,5-AG level was significantly correlated with changes in the glycemic excursion indices of the standard deviation (SD), mean amplitude of glucose excursion (MAGE), lability index, mean postmeal maximum glucose, and area under the curve for glucose above 180 mg/dL (r=-0.576, -0.613, -0.600, -0.630, and -0.500, respectively; all P<0.05). Changes in glycated albumin were correlated with changes in SD and MAGE (r=0.495 and 0.517, respectively; all P<0.05). However, changes in HbA1c were not correlated with any changes in the CGMS variables.

Conclusion

1,5-AG may be a useful marker for the assessment of short-term changes in glycemic variability. Furthermore, 1,5-AG may have clinical implications for the evaluation and treatment of glycemic excursions in type 1 diabetes.

Citations

Citations to this article as recorded by

Glycemic dispersion: a new index for screening high glycemic variability
Rui Shi, Lei Feng, Yan-Mei Liu, Wen-Bo Xu, Bei-Bei Luo, Ling-Tong Tang, Qian-Ye Bi, Hui-Ying Cao
Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef
Digital Behavior Change Interventions to Reduce Sedentary Behavior and Promote Physical Activity in Adults with Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Xiaoyan Zhang, Xue Qiao, Ke Peng, Shan Gao, Yufang Hao
International Journal of Behavioral Medicine.2023;[Epub] CrossRef
DBS are suitable for 1,5-anhydroglucitol monitoring in GSD1b and G6PC3-deficient patients taking SGLT2 inhibitors to treat neutropenia
Joseph P. Dewulf, Nathalie Chevalier, Sandrine Marie, Maria Veiga-da-Cunha
Molecular Genetics and Metabolism.2023; 140(3): 107712. CrossRef
The correlation between serum 1, 5-anhydroglucitol and β-cell function in Chinese adults with different glucose metabolism statuses
Yuexing Yuan, Yuanyuan Tan, Yao Wang, Shanhu Qiu, Jiao Yang, Cheng Chen
International Journal of Diabetes in Developing Countries.2023;[Epub] CrossRef
HbA1c combined with glycated albumin or 1,5‐anhydroglucitol improves the efficiency of diabetes screening in a Chinese population
Junyi Qian, Cheng Chen, Xiaohang Wang, Yuanyuan Tan, Jiao Yang, Yuexing Yuan, Juan Chen, Haijian Guo, Bei Wang, Zilin Sun, Yao Wang
Diabetic Medicine.2022;[Epub] CrossRef
Assessment of glycemia in chronic kidney disease
Mohamed Hassanein, Tariq Shafi
BMC Medicine.2022;[Epub] CrossRef
Continuous subcutaneous insulin infusion alters microRNA expression and glycaemic variability in children with type 1 diabetes
Emma S. Scott, Andrzej S. Januszewski, Luke M. Carroll, Gregory R. Fulcher, Mugdha V. Joglekar, Anandwardhan A. Hardikar, Timothy W. Jones, Elizabeth A. Davis, Alicia J. Jenkins
Scientific Reports.2021;[Epub] CrossRef
Red rice koji extract alleviates hyperglycemia by increasing glucose uptake and glucose transporter type 4 levels in skeletal muscle in two diabetic mouse models
Takakazu Yagi, Koji Ataka, Kai-Chun Cheng, Hajime Suzuki, Keizaburo Ogata, Yumiko Yoshizaki, Kazunori Takamine, Ikuo Kato, Shouichi Miyawaki, Akio Inui, Akihiro Asakawa
Food & Nutrition Research.2020;[Epub] CrossRef
How tightly controlled do fluctuations in blood glucose levels need to be to reduce the risk of developing complications in people with Type 1 diabetes?
R. Livingstone, J. G. Boyle, J. R. Petrie
Diabetic Medicine.2020; 37(4): 513. CrossRef
Resolution on the results of the first working meeting of the scientific advisory board «Actual problems of glycemic variability as a new criterion of glycemic control and safety of diabetes therapy»
Mikhail B. Antsiferov, Gagik R. Galstyan, Alexey V. Zilov, Alexander Y. Mayorov, Tatyana N. Markova, Nikolay A. Demidov, Olga M. Koteshkova, Dmitry N. Laptev, Alisa V. Vitebskaya
Diabetes mellitus.2019; 22(3): 281. CrossRef
Hyperglycemia and Carotenoid Intake Are Associated with Serum Carotenoids in Youth with Type 1 Diabetes
Namrata Sanjeevi, Leah M. Lipsky, Tonja R. Nansel
Journal of the Academy of Nutrition and Dietetics.2019; 119(8): 1340. CrossRef
Correlation of Serum 1,5-AG with Uric Acid in Type 2 Diabetes Mellitus with Different Renal Functions
Kai Zhang, Bizhen Xue, Yuexing Yuan, Yao Wang
International Journal of Endocrinology.2019; 2019: 1. CrossRef
Glycaemic control and glycaemic variability in older people with diabetes
Hermes J Florez
The Lancet Diabetes & Endocrinology.2018; 6(6): 433. CrossRef
Alternate glycemic markers reflect glycemic variability in continuous glucose monitoring in youth with prediabetes and type 2 diabetes
Christine L. Chan, Laura Pyle, Megan M. Kelsey, Lindsey Newnes, Amy Baumgartner, Philip S. Zeitler, Kristen J. Nadeau
Pediatric Diabetes.2017; 18(7): 629. CrossRef
1,5-anidroglucitolo: un marcatore non tradizionale di iperglicemia
Gabriella Lavalle, Roberto Testa, Maria Elisabetta Onori, Raffaella Vero, Anna Vero
La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine.2017; 13(3-4): 139. CrossRef
Glycemic control and variability in association with body mass index and body composition over 18months in youth with type 1 diabetes
Leah M. Lipsky, Benjamin Gee, Aiyi Liu, Tonja R. Nansel
Diabetes Research and Clinical Practice.2016; 120: 97. CrossRef
How Can We Easily Measure Glycemic Variability in Diabetes Mellitus?
Suk Chon
Diabetes & Metabolism Journal.2015; 39(2): 114. CrossRef
Alternative biomarkers for assessing glycemic control in diabetes: fructosamine, glycated albumin, and 1,5-anhydroglucitol
Ji-Eun Lee
Annals of Pediatric Endocrinology & Metabolism.2015; 20(2): 74. CrossRef
Glycemic Variability: How Do We Measure It and Why Is It Important?
Sunghwan Suh, Jae Hyeon Kim
Diabetes & Metabolism Journal.2015; 39(4): 273. CrossRef

Case Report

A Case of Fulminant Type 1 Diabetes with Pulmonary Hypertension.: Do Hyeong Kim, Mi Kyoung Kim, Jun Hoon Jung, Na Rae Kim, Dong Hyeon Rho, Jong Sun Park, Chang Hun Lee, Yoon Sung Cho, Tae Woo Kim, Kyung Il Lee; Korean Diabetes J. 2007;31(5):444-450. Published online September 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.5.444

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Abstract PDF

Some patients with idiopathic type 1 diabetes have a fulminant disorder characterized by the absence of insulitis and of diabetes-related antibodies, a remarkably abrupt onset and high serum pancreatic enzyme concentrations. This is referred to as fulminant type 1 diabetes. Cardiopulmonary disorders are rarely observed around the onset of fulminant type 1 diabetes. A 51-year-old woman suffering from nausea and vomiting was transferred to our hospital. Laboratory findings revealed high blood glucose level and the evidence of diabetic ketoacidosis, but the serum HbA1c was normal nevertheless. The low level of plasma C-peptide indicated the loss of endogenous insulin secretion. The patient satisfied the criteria for the diagnosis of fulminant type 1 diabetes. Electrocardiogram (ECG) revealed nonspecific ST-T-wave abnormalities. Transthoracic echocardiogram demonstrated that she had severe pulmonary hypertension and minimal pericardial effusion. In a week, pulmonary hypertension improved to mild degree without specific treatment. Acute myocarditis was suspected based upon flulike symptoms, nonspecific ST-T-wave abnormalities, minimal pericardial effusion and asymptomatic pulmonary hypertension. We considered it worthwhile reporting this case because fulminant type 1 diabetes with acute myocarditis has never been published yet.

Citations

Citations to this article as recorded by

A Case of Fulminant Type 1 Diabetes Mellitus Complicated with Ischemic Ileitis
Se-Won Oh, Ju-Ri Park, Yun-Jeong Lee, Hee-Yeong Kim, Ji-A Seo, Nan-Hee Kim, Kyung-Mook Choi, Sei-Hyun Baik, Dong-Seop Choi, Sin-Gon Kim
Journal of Korean Endocrine Society.2009; 24(2): 116. CrossRef

Original Article

Prevalence of Diabetic Retinopathy in Diabetics Who are Positive for GAD Autoantibody.: Seon Joong Moon, Chan Hee Lee, Jun Sung Moon, Hee Jung Moon, Ji Eun Lee, Kyung Ah Chun, Ji Sung Yoon, Ihn Ho Cho, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 2007;31(5):429-434. Published online September 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.5.429

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Abstract PDF

BACKGROUND
Diabetic retinopathy is a leading cause of adult blindness. Some patients show early development and progression of diabetic retinopathy despite of apparently good glycemic control. This is suggesting the involvement of other contributing factors. Recent studies have shown that retinopathy and GAD autoantibody (GADA) show an inverse relationship immunologically. This study is designed to investigate the clinical manifestation of diabetes who are positive for GADA and the relationship between GADA and diabetic retinopathy. METHODS: Type 1 diabetic patients & LADA patients who had visited Yeungnam university Medical Center from 1988 to 2005 were involved. We reviewed the pathologic and laboratory records of these patients and investigated the development of diabetic microvascular complications. RESULTS: Compared with patients who had GADA negative diabetes, patients with GADA positive diabetes had lower prevalence of diabetic retinopathy (GADA negative subject: 25.8% vs. GADA positive subject: 9.6%, P < 0.05). CONCLUSION: We confirmed that diabetic retinopathy and GADA showed an inverse relationship. It seems quite probable that GADA may contribute to the prevention of retinopathy. Further research should be needed concerning the effect of GADA on diabetic retinopathy.

Citations

Citations to this article as recorded by

Chronic Complications in Adult Diabetic Patients with and without GAD Antibody
Jin Ook Chung, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung
Korean Diabetes Journal.2009; 33(2): 124. CrossRef

Case Reports

Two Cases of Autoantibody Negative Fulminant Type 1 Diabetes Mellitus.: Hwa Young Cho, Young Min Cho, Myoung Hee Park, Mi Yeon Kang, Ki Hwan Kim, Yun Hyi Ku, Eun Kyung Lee, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; Korean Diabetes J. 2007;31(4):372-376. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.372

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Abstract PDF: Autoantibody negative fulminant type 1 diabetes mellitus is a novel subtype of type 1 diabetes, which is characterized by a remarkably abrupt onset, metabolic derangement such as diabetic ketoacidosis at diagnosis, low HbA1c level at onset and a negative islet-related autoantibodies. The prevalence of fulminant type 1 diabetes has large difference between Japan and other countries. The precise reason for this regional variation remains to be clarified. One of the possible explanations is genetic background such as genotype of class II HLA molecule. In addition, environment factors including viral infection are suggested as possible pathogenesis of the disease. Only a few cases with fulminant type 1 diabetes have been reported outside Japan, and most of these cases with definite diagnosis have been reported in Korea. We report here on two Korean patients that met the criteria for diagnosis of fulminant type 1 diabetes in accordance with their HLA genotypes.

Clinical Courses of Two Women with Gestational Diabetes Mellitus Who are GAD Antibody Positive.: Sung Hoon Yu, Min Jun Song, Sung Hoon Kim, Chang Hoon Yim, Ki Ok Han, Won Kun Park, Hyun Koo Yoon, Ho Yeon Chung; Korean Diabetes J. 2006;30(5):398-402. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.398

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Abstract PDF: Gestational diabetes mellitus (GDM) is defined as glucose intolerance of various degrees with onset or first recognition during pregnancy. Women with GDM are at high risk of developing type 2 diabetes later in life, but the risk of developing type 1 diabetes is also increased. Positivity for glutamic acid decarboxylase (GAD) antibodies during pregnancy confers a high risk for subsequent progression to type 1 diabetes. Here, we reported the two cases with GDM who were GAD antibody positive and progressed to type 1 diabetes with different time-courses. One woman with GDM progressed rapidly to classical type 1 diabetes while the other became slowly progressive IDDM (SPIDDM) [or latent autoimmune diabetes in adults (LADA)].

Original Article

The Clinical Characteristics of Young Onset Diabetes According to Etiology Based Classification.: Mina Park, Yang Il Kang, Suk Chon, Seung joon Oh, Jeong taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim; Korean Diabetes J. 2006;30(3):190-197. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.190

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Abstract PDF

BACKGROUND
Recently, the number of young diabetic patients is increasing. It is important to understand the characteristics of young diabetes and classify it correctly to manage these patients successfully. We aimed to classify young onset diabetes according to etiology and evaluate the clinical characteristics. METHODS: Young patients (15~30 years old) who have been treated diabetes in Kyunghee medical center in 2004 were included. We investigated family history of diabetes, disease duration, body mass index (BMI), the history of diabetic ketoacidosis, HbA1c, fasting C-peptide, autoantibody, lipid profile and treatment method via medical records. RESULT: Total 85 patients (M:F 40:45) were evaluated. Type 1 diabetes was 45.9%, type 2 diabetes was 23.5% and unclassified group was 25.9%. Many type 2 diabetic patients were overweight or obese (94.8%). Most young diabetic patients were using insulin (95.4%). Many type 1 diabetic patients have been treated by insulin only and many type 2 diabetic patients have been received combined therapy of insulin and oral hypoglycemic agent. The recent HbA1c was average 8.32 +/- 2.7%. The prevalence of diabetic retinopathy, neuropathy and nephropathy was 32.9%, 22.4% and 16.4% as each. CONCLUSION: Nearly half of young onset diabetes was type 1 diabetes but many others were also classified to type 2 diabetes or unclassified group. It is important to provide a consistent algorithm for assessment and investigation for newly diagnosed young diabetic patients. More education and effort are required to control diabetes strictly and prevent its complication.

Citations

Citations to this article as recorded by

The Difference in Risk Factors Between Adults With Early-Onset (<40 Years Old) Versus Late-Onset (≥40 Years Old) Type 2 Diabetes in a University Hospital From January 2015-December 2017
Marilyn Katrina C Caro, Elaine C Cunanan
Journal of Medicine, University of Santo Tomas.2022; 6(2): 1009. CrossRef
Lifestyle-related predictors affecting prediabetes and diabetes in 20-30-year-old young Korean adults
Kyong Sil Park, Seon Young Hwang
Epidemiology and Health.2020; 42: e2020014. CrossRef
The Clinical Characteristics of the Newly Diagnosed Early Onset (< 40 Years Old) Diabetes in Outpatients' Clinic
Kyung-Soo Kim, Hyun-Ju Oh, Ji-Woon Kim, Yeo-Kyung Lee, Soo-Kyung Kim, Seok-Won Park, Yoo-Lee Kim, Won-Keun Park, Yong-Wook Cho
Korean Diabetes Journal.2010; 34(2): 119. CrossRef
Anti-GAD Antibody in Patients with Adult-Onset Diabetes in Korea
Eun-Gyoung Hong
Korean Diabetes Journal.2009; 33(1): 13. CrossRef

Case Reports

A Case of Recurrent Hypoglycemic Hemiparesis in an Adult with Type 1 Diabetes Mellitus.: Kyoung Min Kim, Se Hun Kang, Se In Hong, Dong Hyeok Cho, Ho Cheol Kang, Dong Jin Chung, Min Young Chung; Korean Diabetes J. 2006;30(2):136-139. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.136

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Abstract PDF: Transient hypoglycemic hemiparesis is a rare but important presentation of hypoglycemia that is frequently misdiagnosed as stroke. The development of hemiparesis as a result of hypoglycemia was first described in 1928. Thereafter over the years, several cases have been sporadically reported in Korea, but case reports of recurrent hypoglycemic hemiparesis are rare. We recently experienced a case of recurrent hypoglycemic hemiparesis in an adult with type 1 diabetes mellitus. A 30-year-old woman with type 1 diabetes receiving daily multiple subcutaneous insulin injections was admitted with right hemiparesis. She had had admitted with the same symptom and recovered with oral carbohydrates in twice 2 years ago. Her clinical course improved over 2 hours after infusion of dextrose solution. Further investigations such as CT, MRI and MRA revealed no abnormality

A case of Rhino-Orbital Mucormycosis in Newly Diagnosed type 1 Diabetic patient.: Jae Min Lee, Kyu Yuop Hwang, Gi Young Choi, Hyo Jung Nam, Dong Hyun Seo, Sun Hyun Park, Jun hwa Hong, Hyun Jin Kim, Kang Seo Park; Korean Diabetes J. 2005;29(5):495-499. Published online September 1, 2005

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Abstract PDF: Rhino-orbital mucormycosis was a rare, but mostly fatal fungal infection, usually found in poorly controlled diabetics or other immunocompromised hosts. This fungal infection begins from the nose, and rapidly spreads to the paranasal sinus (PNS), orbits and central nervous system(CNS), and finally extends to the entire organ. Early diagnosis and treatment is the only way to increase the survival rate. Herein Is reported We experienced a case of rhino-orbital mucormycosis, with type 1 diabetes mellitus, which was confirmed by a maxillary sinus biopsy. A 38-year-old male had been frequently treated for tonsillitis, but with no history of diabetes mellitus. He was admitted with mental change, accompanied by a fever, facial tenderness and swelling, with progressive visual acuity loss. During admission, CT and MRI of the in orbital area were performed. A biopsy in of the nasal cavity was also performed, and the mucormycosis was diagnosed through the pathological finding. The patient was treated with intravenous amphotericn B and an endoscopic antrostomy.

Two Cases of Fulminant Type 1 Diabetes.: Yu Min Lee, Kyoung Hee Kweon, Seoung Hoon Baek, Ha Young Kim, Byoung Hyun Park, Chung Gu Cho; Korean Diabetes J. 2005;29(4):378-382. Published online July 1, 2005

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Abstract PDF: Type 1 diabetes is characterized by insulin deficiency due to destruction of pancreatic beta-cells. Patients with type 1 diabetes, with no islet autoantibodies, but with acute onset, are classified as having idiopathic of type 1B diabetes. In 2000, this diabetes subtype was described and named "fulminant type 1 diabetes". The clinical characteristics of this subtype of type 1 diabetes are: a remarkably abrupt onset of disease, very short(<1 week) duration of diabetic symptoms, acidosis at diagnosis, negative status of islet-related autoantibodies, virtually no C-peptide secretion(<10 microgram/day in urine), a near normal HbA1c level and an elevated serum pancreatic enzyme level. Since 1988, several cases showing the clinical characteristics of fulminant type diabetes have been reported, with this subtype accounting for approximately 20% of Japanese type 1 diabetes. There have been few cases of fulminant type 1 diabetes in Korea. Herein, our experience of two cases of fulminant type 1 diabetes is reported, with a review of the literature.

Original Articles

Five Year Follow-up of ICA and GADA in Childhood onset Type 1 DM.: Si Hyung Lee, Ji Sung Yoon, Mi Jung Eun, Jin Ho Kim, Yong Ho Park, Kyu Chang Won, Ihn Ho Jo, Hyoung Woo Lee; Korean Diabetes J. 2003;27(5):395-404. Published online October 1, 2003

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Abstract PDF: BACKGROUND
Type 1 diabetes develops due to the destruction of insulin-secreting beta-cells by an autoimmune process, in which both genetic and environmental factors are involved. In children with newly diagnosed type 1 DM, the prevalence of ICA (Islet cell cytoplasmic antibody) is 60~86% and is highest at the time of onset after which it decreases. But, GADA (glutamic acid decarboxylase anti- bodies) are characterized by substantial fluctuations in the humoral immune response over a long period after clinical manifestation. This study was performed to evaluate the persistence of type 1 DM associated autoantibodies, including ICA and GADA, and their relation to clinical characteristics of the disease after clinical manifestation. METHODS: Eighteen childhood onset type 1 diabetes patients (mean age 13.7 years; duration 3.9 years) were included in this study. ICA was measured by indirect immunofluorescence using conventional ICA-IgG and positive samples were titered by serial dilutions. Also the sera were screened for GADA by radioimmuno-assay. RESULTS: The positivities of ICA and GADA at the time of study were 55.6% and 61%, falling to 44.4% and 41.2% 5 years later, respectively. There was no case of an ICA negative patient becoming positive or whose ICA titer was increased later. One case of a GADA negative patient became positive later. Initial c-peptide levels didn't have any correlation with initial ICA titers or ICA prevalence, but did with initial GADA titer. There were significant correlations between initial GADA titer and ICA prevalence (p<0.001), and between initial GADA titer or ICA titer and later ICA persistence (p<0.05). CONCLUSION: ICA and GADA persisted long after the clinical diagnosis of type 1 diabetes. And the persistence of autoantibody positivity showed a weak relation with endogenous insulin secretion and clinical characteristics, both at and after diagnosis of overt type 1 diabetes.

Effect of Mouse Type and Human Type of CpG Oligonucleotide Vaccination on Development of Diabetes in NOD Mice.: Byong Jun Lee, Soo Kie Kim, Eon Sub Park, Hyun Jin Jang, Hyun Chul Cho, Myung Sook Shim, Mi Jin Kim, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 2002;26(6):451-459. Published online December 1, 2002

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Abstract PDF: BACKGROUND
Type 1 diabetes is autoimmune disease and the modulation of immune system could offer breakthrough to the disease. Unmethylated CpG motifs and their oligoneucleotide are potent immunostimulators that can rebalance autoimmune mechanism. To explore DNA based immunotherapy in type 1 diabetes, we vaccinated different types (mouse and human) of CpG ODN to NOD mice. METHODS: Forty 5 week-old female NOD mice were injected with 100 L (10 g) of mouse type CpG ODN or human type CpG ODN or 0.9% normal saline on inguinal area subcutaneously. Seven, 14, and 28 days later we injected to mice same dose of mouse type CpG ODN or human type CpG ODN or normal saline. Blood glucose was measured and mice were sacrificed when they were diabetic. Pancreata and serum were earned from sacrificed NOD mice to evaluate insulitis and insulin immunoassay. RESULTS: Though the final cumulative incidences of diabetes were not significantly different among groups, the tendency of delaying and suppressing the development of diabetes was observed in the early period of vaccination group of CpG ODN. Especially, mouse type CpG ODN was more effective for rodent species than human type CpG ODN. CONCLUSION: This result suggests that immunomodulation therapy using species- specific CpG motif may have a potential to control autoimmune process as well as dissecting T cell milieu in NOD mice.

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.

Humoral Immunological Marks in Patients with Child-onset and Adult-onset Type 1 Diabetes.: Hyun Dae Yoon, Jae Hong Kim, Jung Hyun Oh, Jin Chul Park, Sang Yub Nam, Ji Soon Yoon, Kyu Chang Won, In Ho Cho, Choong Ki Lee, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee, Hyoung Woo Lee; Korean Diabetes J. 2000;24(4):444-456. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 1 diabetes mellitus is an autoimmune disease in which serum antibodies against islet antigens have been recognized. These antibodies include cytoplasmic islet cell antibodies (ICA), and glutamic acid decarboxylase (GAD)65 antibodies and IA2 antibodies. It has been reported that the prevalence of these autoantibodies is different among Caucacian and Asian and Korean type 1 diabetes patients. And the natural course of type 1 diabetes can differ according to the age of onset. But, in contrast to the classic juvenile onset type 1 diabetes, the adult onset type 1 diabetes is poorly characterized about clinical and autoimmune differences at presentation. Thus, this study was perfomed to evaluate clinical and autoimmune characteristics at presentation in subjects with either child onset or adult onset type 1 diabetes and to establish an autoimmune pathogenesis in Korean type 1 diabetes. METHOD: We examined the clinical characteristics of child onset type 1 diabetes (n=32) and adult onset type 1 diabetes (n=40) retrospectively. At the same time, ICA from these patients was measured by standard indirect immunofluorescence, GADA and IA2A from these patients were measured by radioimmunoassay. RESULTS: The mean duration of disease was longer in the adult onset and their serum fasting C-peptide concentration at diagnosis were higer. The prevalence of ICA, GADA, IA2A in sera from 32 patients with child onset type 1 diabetes was 50%, 38% and 31% respectively. And, the prevalence of ICA, GADA and IA2A in sera from 40 patients with adult onset type 1 diabetes was 30%, 25% and 18% respectively.The prevalence of ICA, GADA and IA2A in sera from 39 patients with typical type 1 diabetes was 46%, 30% and 16% respectively. And, the prevalence of ICA, GADA and IA2A in sera from 33 patients with atypical type 1 diabetes was 30%, 30% and 25% respectively. The concordance rate of ICA and GADA in child onset and adult onset diabetes was 81% (26/32), 80% (32/40) respectively. In a subset of these patients with recent onset type 1 diabetes (duration of diabetes < or = 1 year), the prevalence of ICA, GADA and IA2A was 75% (3/4), 75% (3/4), 100% (1/1) respectively, in the child onset type 1 diabetes. CONCLUSION: These observations show that autoantibodies in Korean patients with child onset type 1 diabetes is similar compaired with other Asian groups but is lower than Caucasian patients with type 1 diabetes and the prevalence of humoral immunologic makers in child onset type 1 diabetes was higher than that of adult onset diabetes. These results suggest that autoimmune response is a significant cause of Korean type 1 diabetes but other factors except autoimmunity may play an important role in the pathogenesis of Korean type 1 diabetes.

The Effect of BCG Vaccine on Recent Onset Type 1 Diabetes Mellitus Patients.: Jeong Heon Oh, Sei Hyun Baik, Kyung Mook Choi, Nan Hee Kim, Ie Byung Park, Dong Seop Choi; Korean Diabetes J. 2000;24(3):340-347. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 1 diabetes mellitus (Type 1 DM) results from autoimmune destruction of -cells of the pancreas. Many treatments aimed at inducing remission of newly diagnosed type 1 DM or preventing of type 1 DM in high risk group are being conducted. BCG is known to modulate the development of spontaneous diabetes in animal model of type 1 DM. In some studies, single injection of BCG induced clinical remission in recent onset type 1 DM patients. However, the effect of BCG on human is still controversial. Thus, we performed a prospective study to evaluate the effect of BCG on type 1 DM. METHODS: We enrolled a total of 23 type 1 DM patients within 6 months period. Randomly selected 14 patients were injected 0.1 ml BCG intradermally and 9 patients were injected normal saline. Fasting and postprandial 2 hour C-peptides, and insulin requirements were measured in all patients at enrollment and at 6, 12 and 24 months after BCG vaccination. RESULTS: At enrollment, there was no significant difference in age, sex, duration of diabetes, HbA1-C, body mass index, fasting and postprandial 2 hour C-peptides, and insulin requirement between BCG group and control group. During follow-up, there was no significant difference in fasting and postprandial 2 hour C-peptides. However postprandial 2 hour C-peptides in BCG group were higher than those in control group at 12 and 24 months (p-value>0.05). Insulin requirements also were lower in BCG group than in control group at 12 and 24 months (p-value>0.05). Clinical remission has been sustained in 2 BCG vaccinated patients at 6 and 12 months. In one of the two patients, remission was sustained for 36 months. CONCLUSION: BCG vaccine is safe and convenient to use, however, a large study is warranted for the use of BCG as a therapy of type 1 DM.

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