Diabetes & Metabolism Journal

Brief Report

Genetics
Identification of Two Cases of Ciliopathy-Associated Diabetes and Their Mutation Analysis Using Whole Exome Sequencing: Min Kyeong Kim, Soo Heon Kwak, Shinae Kang, Hye Seung Jung, Young Min Cho, Seong Yeon Kim, Kyong Soo Park; Diabetes Metab J. 2015;39(5):439-443. Published online October 22, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.5.439

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Background

Alström syndrome and Bardet-Biedl syndrome are autosomal recessively inherited ciliopathies with common characteristics of obesity, diabetes, and blindness. Alström syndrome is caused by a mutation in the ALMS1 gene, and Bardet-Biedl syndrome is caused by mutations in BBS1-16 genes. Herein we report genetically confirmed cases of Alström syndrome and Bardet-Biedl syndrome in Korea using whole exome sequencing.

Methods

Exome capture was done using SureSelect Human All Exon Kit V4+UTRs (Agilent Technologies). HiSeq2000 system (Illumina) was used for massive parallel sequencing. Sanger sequencing was used for genotype confirmation and familial cosegregation analysis.

Results

A 21-year old Korean woman was clinically diagnosed with Alström syndrome. She had diabetes, blindness, obesity, severe insulin resistance, and hearing loss. Whole exome sequencing revealed a nonsense mutation in exon 10 of ALMS1 (c.8776C>T, p.R2926X) and a seven base-pair deletion resulting in frameshift mutation in exon 8 (c.6410_6416del, p.2137_2139del). A 24-year-old Korean man had Bardet-Biedl syndrome with diabetes, blindness, obesity, and a history of polydactyly. Whole exome sequencing revealed a nonsynonymous mutation in exon 11 of the BBS1 gene (c.1061A>G, p.E354G) and mutation at the normal splicing recognition site of exon 7 of the BBS1 gene (c.519-1G>T).

Conclusion

We found novel compound heterozygous mutations of Alström syndrome and Bardet-Biedl syndrome using whole exome sequencing. The whole exome sequencing successfully identified novel genetic variants of ciliopathy-associated diabetes.

Citations

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Genotype–phenotype associations in Alström syndrome: a systematic review and meta-analysis
Brais Bea-Mascato, Diana Valverde
Journal of Medical Genetics.2024; 61(1): 18. CrossRef
Differentiating Monogenic and Syndromic Obesities From Polygenic Obesity: Assessment, Diagnosis, and Management
Angela K. Fitch, Sonali Malhotra, Rushika Conroy
Obesity Pillars.2024; : 100110. CrossRef
Whole exome sequencing identifies rare biallelic ALMS1 missense and stop gain mutations in familial Alström syndrome patients
Naglaa M. Kamal, Ahmed N. Sahly, Babajan Banaganapalli, Omran M. Rashidi, Preetha J. Shetty, Jumana Y. Al-Aama, Noor A. Shaik, Ramu Elango, Omar I. Saadah
Saudi Journal of Biological Sciences.2020; 27(1): 271. CrossRef
Established and emerging strategies to crack the genetic code of obesity
V. Tam, M. Turcotte, D. Meyre
Obesity Reviews.2019; 20(2): 212. CrossRef
Identifying Pathogenic Variants of Monogenic Diabetes Using Targeted Panel Sequencing in an East Asian Population
Seung Shin Park, Se Song Jang, Chang Ho Ahn, Jung Hee Kim, Hye Seung Jung, Young Min Cho, Young Ah Lee, Choong Ho Shin, Jong Hee Chae, Jae Hyun Kim, Sung Hee Choi, Hak C Jang, Jee Cheol Bae, Jong Cheol Won, Sung-Hoon Kim, Jong-Il Kim, Soo Heon Kwak, Kyong
The Journal of Clinical Endocrinology & Metabolism.2019; 104(9): 4188. CrossRef
Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes
Sheila Castro-Sánchez, María Álvarez-Satta, Mohamed A. Tohamy, Sergi Beltran, Sophia Derdak, Diana Valverde, Anand Swaroop
PLOS ONE.2017; 12(8): e0183081. CrossRef

Original Articles

Prevalence and Clinical Characteristics of Recently Diagnosed Type 2 Diabetes Patients with Positive Anti-Glutamic Acid Decarboxylase Antibody: Yul Hwangbo, Jin Taek Kim, Eun Ky Kim, Ah Reum Khang, Tae Jung Oh, Hak Chul Jang, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, Young Min Cho; Diabetes Metab J. 2012;36(2):136-143. Published online April 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.2.136

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Abstract PDF PubReader

Background

Latent autoimmune diabetes in adults (LADA) refers to a specific type of diabetes characterized by adult onset, presence of islet auto-antibodies, insulin independence at the time of diagnosis, and rapid decline in β-cell function. The prevalence of LADA among patients with type 2 diabetes varies from 2% to 20% according to the study population. Since most studies on the prevalence of LADA performed in Korea were conducted in patients who had been tested for anti-glutamic acid decarboxylase antibody (GADAb), a selection bias could not be excluded. In this study, we examined the prevalence and clinical characteristics of LADA among adult patients recently diagnosed with type 2 diabetes.

Methods

We included 462 patients who were diagnosed with type 2 diabetes within 5 years from the time this study was performed. We measured GADAb, fasting insulin level, fasting C-peptide level, fasting plasma glucose level, HbA1c, and serum lipid profiles and collected data on clinical characteristics.

Results

The prevalence of LADA was 4.3% (20/462) among adult patients with newly diagnosed type 2 diabetes. Compared with the GADAb-negative patients, the GADAb-positive patients had lower fasting C-peptide levels (1.2±0.8 ng/mL vs. 2.0±1.2 ng/mL, P=0.004). Other metabolic features were not significantly different between the two groups.

Conclusion

The prevalence of LADA is 4.3% among Korean adult patients with recently diagnosed type 2 diabetes. The Korean LADA patients exhibited decreased insulin secretory capacity as reflected by lower C-peptide levels.

Citations

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The worldwide prevalence of latent autoimmune diabetes of adults among adult-onset diabetic individuals: a systematic review and meta-analysis
Deepika Ramu, Selvaraj Ramaswamy, Suresh Rao, Solomon F. D. Paul
Endocrine.2023; 82(1): 28. CrossRef
Investigation of serum level relationship anti-glutamic acid decarboxylase antibody and inflammatory cytokines (IL1-β, IL-6) with vitamins D in type 2 diabetes
Vahid Pouresmaeil, Sarmad Mashayekhi, Mohammad Sarafraz Yazdi
Journal of Diabetes & Metabolic Disorders.2022; 21(1): 181. CrossRef
Recent information on test utilization and intraindividual change in anti-glutamic acid decarboxylase antibody in Korea: a retrospective study
Rihwa Choi, Wonseo Park, Gayoung Chun, Jiwon Lee, Sang Gon Lee, Eun Hee Lee
BMJ Open Diabetes Research & Care.2022; 10(3): e002739. CrossRef
Prevalence and factors associated with latent autoimmune diabetes in adults (LADA): a cross-sectional study
Anselmo M. Manisha, Aminiel R. Shangali, Sayoki G. Mfinanga, Erasto V. Mbugi
BMC Endocrine Disorders.2022;[Epub] CrossRef
Latent Autoimmune Diabetes in Adults (LADA) and its Metabolic Characteristics among Yemeni Type 2 Diabetes Mellitus Patients
Dhekra Al-Zubairi, Molham AL-Habori, Riyadh Saif-Ali
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2021; Volume 14: 4223. CrossRef
Therapeutic approaches for latent autoimmune diabetes in adults: One size does not fit all
Theocharis Koufakis, Niki Katsiki, Pantelis Zebekakis, George Dimitriadis, Kalliopi Kotsa
Journal of Diabetes.2020; 12(2): 110. CrossRef
Long‐term effects on glycaemic control and β‐cell preservation of early intensive treatment in patients with newly diagnosed type 2 diabetes: A multicentre randomized trial
Suk Chon, Sang Youl Rhee, Kyu Jeung Ahn, Sei Hyun Baik, Yongsoo Park, Moon Suk Nam, Kwan Woo Lee, Soon Jib Yoo, Gwanpyo Koh, Dae Ho Lee, Young Seol Kim, Jeong‐Taek Woo
Diabetes, Obesity and Metabolism.2018; 20(5): 1121. CrossRef
A Global Perspective of Latent Autoimmune Diabetes in Adults
Rajashree Mishra, Kenyaita M. Hodge, Diana L. Cousminer, Richard D. Leslie, Struan F.A. Grant
Trends in Endocrinology & Metabolism.2018; 29(9): 638. CrossRef
The prevalence of latent autoimmune diabetes in adults and its correlates in patients with type 2 diabetes in Kerman, Iran [2011]
Gozashti Mohammad Hossein, Shafiei Maryam, Esmaeilian Saeed, Najafipour Hamid, Mashrouteh Mahdieh
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2015; 9(2): 104. CrossRef
Low prevalence of latent autoimmune diabetes in adults in northern India
A. Sachan, G. Zaidi, R. P. Sahu, S. Agrawal, P. G. Colman, E. Bhatia
Diabetic Medicine.2015; 32(6): 810. CrossRef
Amelioration of Diabetes-induced Cognitive Deficits by GSK-3β Inhibition is Attributed to Modulation of Neurotransmitters and Neuroinflammation
Ashok Kumar Datusalia, Shyam Sunder Sharma
Molecular Neurobiology.2014; 50(2): 390. CrossRef
Successful treatment of latent autoimmune diabetes in adults with Traditional Chinese Medicine: a case report
Jiaxing Tian, Wenke Liu, Zhong Zhen, Xiaolin Tong
Journal of Traditional Chinese Medicine.2013; 33(6): 766. CrossRef
Clinical characteristics and insulin independence of Koreans with new‐onset type 2 diabetes presenting with diabetic ketoacidosis
H. Seok, C. H. Jung, S. W. Kim, M. J. Lee, W. J. Lee, J. H. Kim, B‐W. Lee
Diabetes/Metabolism Research and Reviews.2013; 29(6): 507. CrossRef
A Case of Latent Autoimmune Diabetes in Adults Developed after Surgical Cure of Growth Hormone Secreting Pituitary Tumor
Wonjin Kim, Jung Ho Kim, Youngsook Kim, Ji Hye Huh, Su Jin Lee, Mi Sung Park, Eun Yeong Choe, Jeong Kyung Park, Myung Won Lee, Jae Won Hong, Byung Wan Lee, Eun Seok Kang, Bong Soo Cha, Eun Jig Lee, Hyun Chul Lee
Endocrinology and Metabolism.2012; 27(4): 318. CrossRef
Latent Autoimmune Diabetes in Adults: Autoimmune Diabetes in Adults with Slowly Progressive β-cell Failure
Hannah Seok, Byung Wan Lee
Diabetes & Metabolism Journal.2012; 36(2): 116. CrossRef

Carotid Intimal-Medial Thickness Is Not Increased in Women with Previous Gestational Diabetes Mellitus: Yun Hyi Ku, Sung Hee Choi, Soo Lim, Young Min Cho, Young Joo Park, Kyong Soo Park, Seong Yeon Kim, Hak Chul Jang; Diabetes Metab J. 2011;35(5):497-503. Published online October 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.5.497

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Abstract PDF PubReader

Background

Gestational diabetes mellitus (GDM) is known to increase the risk of cardiovascular diseases. Measuring the carotid artery intimal-medial thickness (CIMT) is a non-invasive technique used to evaluate early atherosclerosis and to predict future cardiovascular diseases. We examined the association between CIMT and cardiovascular risk factors in young Korean women with previous GDM.

Methods

One hundred one women with previous GDM and 19 women who had normal pregnancies (NP) were recruited between 1999 and 2002. At one year postpartum, CIMT was measured using high-resolution B-mode ultrasonography, and oral glucose tolerance tests were performed. Fasting glucose, glycated hemoglobin A1c (HbA1c), insulin levels and lipid profiles were also measured. CIMTs in the GDM and NP groups were compared, and the associations between CIMT and cardiovascular risk factors were analyzed in the GDM group.

Results

CIMT results of the GDM group were not significantly different from those of the NP group (GDM, 0.435±0.054 mm; NP, 0.460±0.046 mm; P=0.069). In the GDM group, a higher HbA1c was associated with an increase in CIMT after age adjustment (P=0.011). CIMT results in the group with HbA1c >6.0% were higher than those of the normal HbA1c (HbA1c ≤6.0%) (P=0.010). Nine of the patients who are type 2 diabetes mellitus converters within one year postpartum but showed no significant difference in CIMT results compared to NP group.

Conclusion

Higher HbA1c is associated with an increase in CIMT in women with previous GDM. However, CIMT at one year postpartum was not increased in these women compared to that in NP women.

Citations

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The effect of gestational diabetes mellitus on carotid artery intima-media thickness in and after pregnancy: a systematic review and meta-analysis
Andrea Sonaglioni, Elisabetta Piergallini, Angelo Naselli, Gian Luigi Nicolosi, Anna Ferrulli, Stefano Bianchi, Michele Lombardo, Giuseppe Ambrosio
Acta Diabetologica.2023; 61(2): 139. CrossRef
Prognostic indicators of persistent carotid intima-media thickness increase in postpartum period in a population of normotensive women with gestational diabetes mellitus
Andrea Sonaglioni, Gian Luigi Nicolosi, Valentina Esposito, Stefano Bianchi, Michele Lombardo
European Journal of Obstetrics & Gynecology and Reproductive Biology.2022; 269: 47. CrossRef
Pharmacotherapy for gestational diabetes
Angelo Maria Patti, Rosaria Vincenza Giglio, Kalliopi Pafili, Manfredi Rizzo, Nikolaos Papanas
Expert Opinion on Pharmacotherapy.2018; 19(13): 1407. CrossRef
Women with a history of gestational diabetes on long-term follow up have normal vascular function despite more dysglycemia, dyslipidemia and adiposity
Olubukola Ajala, Louise A. Jensen, Edmond Ryan, Constance Chik
Diabetes Research and Clinical Practice.2015; 110(3): 309. CrossRef
Gestational Diabetes Mellitus in Korean Women: Similarities and Differences from Other Racial/Ethnic Groups
Catherine Kim
Diabetes & Metabolism Journal.2014; 38(1): 1. CrossRef
History of Gestational Diabetes Mellitus and Future Risk of Atherosclerosis in Mid‐life: The Coronary Artery Risk Development in Young Adults Study
Erica P. Gunderson, Vicky Chiang, Mark J. Pletcher, David R. Jacobs, Charles P. Quesenberry, Stephen Sidney, Cora E. Lewis
Journal of the American Heart Association.2014;[Epub] CrossRef
Association of Gestational Diabetes Mellitus (GDM) with subclinical atherosclerosis: a systemic review and meta-analysis
Jing-Wei Li, Si-Yi He, Peng Liu, Lin Luo, Liang Zhao, Ying-Bin Xiao
BMC Cardiovascular Disorders.2014;[Epub] CrossRef
Cardiovascular Disease Risk in the Offspring of Diabetic Women: The Impact of the Intrauterine Environment
Laura J. Marco, Kate McCloskey, Peter J. Vuillermin, David Burgner, Joanne Said, Anne-Louise Ponsonby
Experimental Diabetes Research.2012; 2012: 1. CrossRef
The Association between Carotid Atherosclerosis and Glucose
Bo Kyung Koo
Diabetes & Metabolism Journal.2011; 35(5): 466. CrossRef

Prevalence and Clinical Characteristics of Aspirin Resistance in the Patients with Type 2 Diabetes Mellitus.: Mi Yeon Kang, Young Min Cho, Hyun Kyung Kim, Jee Hyun An, Hwa Young Ahn, Ji Won Yoon, Hoon Sung Choi, Jie Seon Lee, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2008;32(1):53-59. Published online February 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.1.53

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Abstract PDF

BACKGROUND
We examined the prevalence and clinical characteristics of aspirin resistance in the Korean patients with type 2 diabetes mellitus. METHODS: We studied 181 Korean patients with type 2 diabetes mellitus who were taking aspirin (100 mg/day for > or = 3 months) and no other antiplatelet agents. The VerifyNow System was used to determine aspirin responsiveness. Aspirin resistance was defined as an aspirin reaction unit (ARU) > or = 550. We measured the cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) to evaluate arteriosclerosis. The anthropometric parameters, electrocardiogram, blood pressure, fasting plasma glucose, lipid profiles, hemoglobin A1c, highly sensitive C-reactive protein (hsCRP), homocysteine, and microalbuminuria were measured in each patient. RESULTS: The prevalence of aspirin resistance in type 2 diabetic patients was 9.4% (17 of 181). Those who had aspirin resistance were older than those without aspirin resistance (64.6 +/- 10.6 vs. 59.8 +/- 8.1, P = 0.024). Aspirin resistance was not associated with fasting plasma glucose, total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, hemoglobin A1c, hsCRP, homocysteine, microalbuminuria, ABI, CAVI, and body mass index. CONCLUSION: Prevalence of aspirin resistance in the Korean patients with type 2 diabetes mellitus was 9.4%. Although aspirin resistance was associated with old age, we could not find any good clinical parameter to predict it. Therefore, aspirin resistance should be evaluated in diabetic patients taking aspirin for prevention of cardiovascular complications.

Citations

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Long Non-Coding RNA H19 Positively Associates With Aspirin Resistance in the Patients of Cerebral Ischemic Stroke
Jue Wang, Bin Cao, Yan Gao, Dong Han, Haiping Zhao, Yuhua Chen, Yumin Luo, Juan Feng, Yanxia Guo
Frontiers in Pharmacology.2020;[Epub] CrossRef
6^th Asian PAD Workshop

Annals of Vascular Diseases.2015; 8(2): 135. CrossRef
Non-HDL cholesterol is an independent risk factor for aspirin resistance in obese patients with type 2 diabetes
Jong Dai Kim, Cheol-Young Park, Kue Jeong Ahn, Jae Hyoung Cho, Kyung Mook Choi, Jun Goo Kang, Jae Hyeon Kim, Ki Young Lee, Byung Wan Lee, Ji Oh Mok, Min Kyong Moon, Joong Yeol Park, Sung Woo Park
Atherosclerosis.2014; 234(1): 146. CrossRef

Case Report

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.

Original Articles

The Association of Aldose Reductase Gene Polymorphisms with Neuropathy in Patients with Type 2 Diabetes.: In Kyong Jeong, Kyong Soo Park, Min Kyong Moon, Jae Hyeon Kim, Chan Soo Shin, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2007;31(3):274-283. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.274

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Abstract PDF

BACKGROUND
Previous studies have suggested that polymorphisms in and around the aldose reductase (AR) gene are associated with the development of diabetic microvascular disease. This study explored the hypothesis that the polymorphisms of the (A-C)n dinucleotide repeat sequence, located at 2.1 kilobase (kb) upstream of the transcription start site of AR gene, modulate the risk of diabetic neuropathy (DN). METHODS: 66 patients with DN, 30 without microvascular complications (MC) after 20 years of diabetes, and 87 normal healthy controls were studied. To test highly polymorphic microsatellite marker 2.1 kb upstream of the initiation site of the AR gene, we performed polymerase chain reaction using the primer labeled with fluorescent dye and GeneScan by ABI prism 377 automated DNA sequencer and ABI Genotyper software 2.0. RESULTS: Seven alleles (Z-6, Z-4, Z-2, Z, Z+2, Z+4 and Z+6) were identified. Z-2 allele was more frequently observed in patients with DN (77.3%) than in those without MC (43.3%, P = 0.007). The subgroup of patients who developed DN within 5 years after the diagnosis of diabetes also had higher frequency of Z-2 allele (91.7%) compared to those without MC (43.3%, P = 0.028). On the contrary, Z+6 allele tended to be more frequent in patients without MC (10.0%) than in those with DN (0%, P = 0.063). CONCLUSION: These results support the hypothesis that environmental-genetic interactions may modulate the risk of neuropathy in patients with diabetes. Particularly, the Z-2 allele, in the presence of diabetes, may be associated with the development of DN.

Citations

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The Association between Serum GGT Concentration and Diabetic Peripheral Polyneuropathy in Type 2 Diabetic Patients
Ho Chan Cho
Korean Diabetes Journal.2010; 34(2): 111. CrossRef

Efficacy Evaluation of Atorvastatin in Korean Hyperlipidemic Patients with Type 2 Diabetes Mellitus.: Dong Seop Choi, Duk Kyu Kim, Doo Man Kim, Seong Yeon Kim, Moon Suk Nam, Yong Soo Park, Ho Sang Shon, Chul Woo Ahn, Kwan Woo Lee, Ki Up Lee, Moon Kyu Lee, Choon Hee Chung, Bong Yeon Cha; Korean Diabetes J. 2006;30(4):292-302. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.292

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Abstract PDF

BACKGROUND
NCEP ATP III Guideline recommends aggressive treatments of diabetic dyslipidemia, recognizing diabetes mellitus as CHD risk equivalents. This study was conducted to evaluate the effectiveness and safety of atorvastatin in hyperlipidemic patients with Type 2 diabetes mellitus through post-marketing drug use investigation of atorvastatin. METHODS: An open, multi-center, non-comparison, titrated dosage study was conducted in hyperlipidemic patients, who were treated with atorvastatin at first visiting hospitals from Mar. 2004 to Sep. 2004. 96 endocrinologists participated from 66 centers in this study. Total 2,182 hyperlipidemic patients were enrolled and 1,514 patients among them were accompanied by diabetes mellitus. Efficacy was evaluated at later than 4-week treatment by % change of total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol from baseline. Percent of patients reaching LDL-cholesterol level less than 100 mg/dL was also analyzed. The adverse events incidence and abnormalities of clinical laboratory values were evaluated for safety monitoring. RESULTS: Total cholesterol, triglycerides, and LDL-cholesterol level were reduced by 26.6%, 12.0%, and 34.8%, respectively, in diabetic hyperlipidemic patients after atorvastatin treatment. The patients with LDL-cholesterol level of less than 100 mg/dL were increased from 2.8% to 52.6%. Atorvastatin was considered to be safe because adverse drug reactions were reported in 32 patients (1.5%) of total 2,182 patients. CONCLUSION: Atorvastatin was effective and safe in hyperlipidemic patients with type 2 diabetes mellitus.

Citations

Citations to this article as recorded by

Response: A Retrospective Study on the Efficacy of a Ten-Milligram Dosage of Atorvastatin for Treatment of Hypercholesterolemia in Type 2 Diabetes Mellitus Patients (Korean Diabetes J 2010;34:359-67)
Dong Kyun Kim, Sa Rah Lee, Min Sik Kim, Suk Hyang Bae, Jin Yeon Hwang, Jung-Min Kim, Sung Hwan Suh, Hye-Jeong Lee, Mi Kyoung Park, Duk Kyu Kim
Diabetes & Metabolism Journal.2011; 35(1): 88. CrossRef
A Retrospective Study on the Efficacy of a Ten-Milligram Dosage of Atorvastatin for Treatment of Hypercholesterolemia in Type 2 Diabetes Mellitus Patients
Dong Kyun Kim, Sa Rah Lee, Min Sik Kim, Suk Hyang Bae, Jin Yeon Hwang, Jung-Min Kim, Sung Hwan Suh, Hye-Jeong Lee, Mi Kyoung Park, Duk Kyu Kim
Korean Diabetes Journal.2010; 34(6): 359. CrossRef
The Association of Plasma HDL-Cholesterol Level with Cardiovascular Disease Related Factors in Korean Type 2 Diabetic Patients
Hye Sook Hong, Jong Suk Park, Han Kyoung Ryu, Wha Young Kim
Korean Diabetes Journal.2008; 32(3): 215. CrossRef

Increasing Trends of Metabolic Syndrome in Korea -Based on Korean National Health and Nutrition Examination Surveys-.: Soo Lim, Eun Jung Lee, Bo Kyeong Koo, Sung Il Cho, Kyong Soo Park, Hak Chul Jang, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2005;29(5):432-439. Published online September 1, 2005

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Abstract PDF: BACKGOUND: The number of individuals with metabolic syndrome is increasing in Asian as well as in Western countries. The aim of this study was to compare the prevalence and patterns of metabolic syndrome as determined by the 1998 and 2001 Korean National Health and Nutrition Examination Surveys(KNHANES). METHODS: A total of 6,907 and 4,536 Koreans aged over 20 years participated in the KNHANES in 1998 and 2001, respectively. A stratified multistage probability sampling design and weighting adjustments were made to obtain a representative Korean population. The working definition of the National Cholesterol Education Program-Adult Treatment Panel III was used to define metabolic syndrome. The International Obesity Task Force criteria for the Asian-Pacific population were used to determine waist circumference criteria. RESULTS: The age-adjusted prevalence of metabolic syndrome significantly increased from 22.5 to 24.1% between 1998 and 2001(P<0.01). Of the five components composing metabolic syndrome, low HDL-cholesterolemia showed the highest increase(32.6%) over this period, followed by hypertriglyceridemia and abdominal obesity, with 15.9% and 4.3% increases, respectively. In contrast, the number of subjects with high blood pressure or elevated fasting glucose levels were reduced(37.1-->33.1% and 18.9-->15.4%, respectively, both P<0.01). CONCLUSION: Dyslipidemia and abdominal obesity were primarily responsible for the increase in metabolic syndrome in Korea over the period 1998 to 2001. Changes to diet patterns and a reduction in physical activity are likely to have contributed to the rapid increase in metabolic syndrome in Korea; therefore, national strategies will be needed to counteract this increase.

Glutathion S-Transferase M1 Gene Polymorphism is Associated with Type 2 Diabetic Nephropathy.: Jae Hyeon Kim, Min Kyong Moon, Sang Wan Kim, Hyoung Doo Shin, Young Hwan Hwang, Curie Ahn, Hak Cheol Jang, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2005;29(4):315-321. Published online July 1, 2005

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Abstract PDF: BACKGROUND
Oxidative stress may be a determinant of the development of diabetic nephropathy. Glutathione S-transferases(GST) can work as an endogenous antioxidant to protect cells from oxidative stress. Homozygous deletion of the mu and theta subclasses of GST(GST-M1 and GST-T1), and Val105Ile polymorphism of the pi subclass of GST(GST-P1) are associated with antioxidant enzyme activity. In this study, whether the Val105Ile of GST-P1, null genotype of GST-M1 and GST-T1 are associated with type 2 diabetic nephropathy were examined. METHODS: These GST subclasses were genotyped in 361 type 2 diabetic patients with retinopathy; the subjects were divided into two groups, those with an end stage renal disease(ESRD)(the case group n=177) and those(the control group, n=184) showing no signs of renal involvement. RESULTS: The frequencies of the GST-P1 Ile105Val and GST-T1 null genotypes were no different between the cases and controls. However, the frequency of the GST-M1 null genotype was significantly higher in the cases than the controls(61.7% vs. 51.1%, chi-square=4.09, P=0.043), which was still significant after correction for age, sex and duration of diabetes (P= 0.044). In addition, the GST-M1 null genotype showed an increased frequency between the controls and the cases with long and short durations of type 2 diabetes until the onset of ESRD(51.1, 58.9 and 65.5%, respectively; chi-square for trend=5.12, P=0.024). CONCLUSION: This is the first study to suggest that the GST-M1 gene polymorphism might contribute to the development of ESRD in type 2 diabetic patients.

Pregnancy Outcome in Korean Women with Gestational Diabetes Mellitus Diagnosed by the Carpenter-Coustan Criteria.: Hak Chul Jang, Young Min Cho, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, Moon Young Kim, Jae Hyug Yang, Son Moon Shin; Korean Diabetes J. 2004;28(2):122-130. Published online April 1, 2004

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Abstract PDF: BACKGROUND
The American Diabetes Association recently proposed the Carpenter-Coustan criteria for the diagnosis of gestational diabetes mellitus(GDM) based on the results of the Toronto Tri-Hospital Study. The prevalence of GDM in Korean women increased, on average, by 60% when the Carpenter-Coustan criteria were applied. However, the pregnancy outcome of Korean women with GDM with regard to the Carpenter-Coustan criteria tremains to be reported. The pregnancy outcomes of those Korean women with GDM by the Carpenter- Coustan criteria, but not by the NDDG criteria were assessed. METHODS: In this study, a total of 2776 pregnant women underwent universal screening for GDM, between January 1993 and December 1994, as recommended by the Third International Workshop-Conference on Gestational Diabetes Mellitus with minor modifications. The primary pregnancy outcomes were preeclampsia, premature delivery, delivery by C-section, birth weight and LGA infants. RESULTS: Of the 2776 women, 656 screened-positive for GDM. Of these, 37 and 74 had GDM by the Carpenter-Coustan and NDDG criteria, respectively. With increasing glucose intolerance, there was a stepwise increase in premature deliveries, deliveries by C-section and preeclampsia from those screening negative to GDM by the NDDG criteria, with a similar trend for the frequency of LGA infants. The LGA infant screening-negative and positive were 13.5 and 16.1%, but those with a normal glucose tolerance were 27.0 and 33.8% in those screening positive to GDM by the Carpenter-Coustan and NDDG criteria, respectively(P<0.001). CONCLUSION: Our study demonstrated that increasing glucose tolerance was associated with increasing frequencies of adverse pregnancy outcomes in Korean women. The maternally complicated and LGA infants were significantly higher in women with GDM by the Carpenter-Coustan criteria. Thus the Carpenter- Coustan criteria are recommended for the diagnosis of GDM in Korean Women.

Common Genetic Polymorphisms in the Promoter of Resistin Gene are Major Determinants of Plasma Resistin Concentrations in Humans.: Young Min Cho, Byung Soo Youn, Sung Soo Chung, Ki Woo Kim, Bo Kyeong Koo, Kang Yeol Yu, Hong Je Park, Hyoung Doo Shin, Hak Chul Jang, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2004;28(1):9-19. Published online February 1, 2004

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Abstract PDF: BACKGROUND
Resistin has been postulated to be an important link between obesity and insulin resistance. Genetic polymorphisms in the resistin gene promotor have been suggested as a determinant of the expression of resistin mRNA, which is possibly associated with obesity and insulin resistance. In this study, the association between the genotype of the resistin promoter, and its plasma concentrations, were investigated. METHODS: The g.-537A>C and g.-420C>G polymorphisms in the resistin promoter were examined, and the levels of plasma resistin measured in the Korean subjects, both with and without type 2 diabetes. Haplotype-based promoter activity and the gel electrophoretic mobility-shift assays(EMSA) were also performed. RESULTS: The -420G and the -537A alleles, which were in linkage disequilibrium, were associated with higher plasma resistin concentrations. Individuals with the A-G(-537 A and -420G) haplotypes showed significantly higher plasma resistin levels than those that did not. The haplotypes A-G had modestly increased promoter activities compared to the other haplotypes. The EMSA revealed the -420 G allele to be specific for binding of the nuclear proteins from adipocytes and monocytes. However, neither polymorphism was associated with type 2 diabetes or obesity in our study subjects. CONCLUSION: Polymorphisms in the promoter of the resistin gene are major determinants of plasma resistin concentrations in humans

Randomized Controlled Trial

The Effects of Insulin Sensitizers on the Plasma Concentrations of Adipokines in Type 2 Diabetic Patients.: Hye Seung Jung, Young Min Cho, Kyung Won Kim, Byung Soo Youn, Kang Yeol Yu, Hong Je Park, Chan Soo Shin, Seong Yeon Kim, Hong Kyu Lee, Kyong Soo Park; Korean Diabetes J. 2003;27(6):476-489. Published online December 1, 2003

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Abstract PDF: BACKGROUND
Resistin, leptin and adiponectin are proteins secreted from adipose tissue, and have been suggested to play roles in insulin sensitivity. The effects of the circulating levels of two different types of insulin sensitizer, rosiglitazone and metformin, in type 2 diabetic patients were examined to elucidate the relationship between adipokines and insulin resistance. METHODS: Thirty type 2 diabetic patients, who showed poor glycemic control when administered 4 mg glimepiride a day, without severe diabetic complications or medical illness, were randomized to receive an additional 4mg rosiglitazone or 1000 mg metformin a day. The plasma resistin, leptin and adiponectin concentrations were measured at the baseline and after 6 months of treatment. The anthropometric parameters, fasting plasma glucose, HbA1C, total cholesterol, triglyceride, HDL-cholesterol and free fatty acids were also measured. Certain single nucleotide polymorphisms of adipokine genes were also identified. RESULTS: There were no significant differences in the reductions of the plasma glucose and HbA1C levels, after 6 months of treatment, between the two groups. The plasma resistin concentrations decreased, the adiponectin significantly increased and the leptin showed a tendency to increase in the rosiglitazone group. In the metformin group, only the resistin concentration significantly increased. However, the changes in the adipokines did not correlate with the HOMA-IR in either group. The reduction in the HbA1C due to rosiglitazone was greater if the initial leptin level was high, if there was a G allele on the -420th locus of the resistin gene, or the 45th locus of the APM1 (adiponectin gene) was the T-homozygote or there was a T allele on the 276th locus of the APM1. Those due to metfromin were greater with high initial adiponectin levels. CONCLUSION: In type 2 diabetic patients, showing poor glycemic control with sulfonylurea therapy, rosiglitazone or metformin treatment changed some of the adipokine concentrations, but these changes were not clearly related with insulin resistance. Polymorphisms of certain adipokine genes seem to have a relation to the susceptibility of rosiglitazone.

Original Articles

Plasminogen Activator Inhibitor-1 (PAI-1)/tissue Plasminogen Activator (t-PA) Levels and PAI-1 4G/5G Promoter Polymorphism in Type 2 Diabetes with Microalbuminuria.: Seong Hee Kwon, Young Joo Park, In Kyong Jeong, Jae Joon Koh, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2003;27(3):186-198. Published online June 1, 2003

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Abstract PDF: BACKGROUND
Persistent microalbuminuria in diabetic patients is a risk factor of cardiovascular mortality. Increased plasma plasminogen activator inhibitor type-1 (PAI-1) levels have been observed in diabetic patients with overt nephropathy. However, there have been few studies on diabetic patients with microalbuminuria. The expression of PAI-1 may be influenced by the polymorphism of the PAI-1 genotype promoter. The aim of this study was to investigate the relationship between the plasma PAI-1/t-PA levels, polymorphism of the PAI-1 4G/5G promoter and microalbuminuria in type 2 diabetes. METHODS: The plasma PAI-1/t-PA levels and polymorphisms of the PAI-1 promoter were measured in type 2 diabetic patients without nephropathy (n=30), and with microalbuminuria (n=30) and overt proteinuria (n=20). The correlation between the amount of urinary albumin excretion and plasma PAI-1/t-PA levels were investigated using Pearson's correlation analyses. RESULTS: The plasma PAI-1/t-PA levels and polymorphisms of the PAI-1 promoter showed no significant difference between the three groups in relation to the urinary albumin excretion. There were no differences in the plasma PAI-1/t-PA levels between the genotypes of the polymorphism of the PAI-1 promoter. No association was found between the amount of urinary albumin excretion and the plasma PAI-1/t-PA levels and genotypes of the polymorphism of the PAI-1 promoter. CONCLUSION: These results show that there was no decrease in the fibrinolytic state in type 2 diabetics with microalbuminuria, compared to normoalbuminuria, which also suggest that polymorphisms of the PAI-1 4G/5G promoter do not affect the plasma PAI-1/t-PA levels in type 2 diabetic patients with microalbuminuria.

Clinical Characteristics of Post-transplantation Diabetes Mellitus associated with Tacrolimus Therapy after Kidney Transplantation.: Young Min Cho, Hye Seung Jung, Yun Yong Lee, Min Kyong Moon, Suk Kyung Kim, Hyun Jung Jeon, Curie Ahn, Jong Won Ha, Sang Joon Kim, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2002;26(6):509-519. Published online December 1, 2002

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Abstract PDF: BACKGROUND
Post-transplantion diabetes mellitus (PTDM) is a major metabolic complication of transplantation and shows a variable incidence among studies with different population or different definition. We examined the incidence and the risk factors of PTDM in the Korean patients with tacrolimus-based immunosuppression following kidney transplantation, and also investigated the change of insulin secretory capacity. METHODS: Twenty-one patients using tacrolimus as primary immunosuppressant were recruited and tested with serial 75-g oral glucose tolerance test (OGTT) at 0, 1, 3, and 6 months after kidney transplantation. RESULTS: According to the American Diabetes Association criteria, the incidence of PTDM was 57.1% (12 of 21). Baseline characteristics of PTDM group were old age (especially > 40 yr), high body mass index, high fasting glucose, high plasma insulin, and increased insulin resistance. The insulin secretory capacity in PTDM group was maximally suppressed 3 months after transplantation and was gradually restored thereafter along with dose reduction of tacrolimus. CONCLUSIONS: Attention should be paid to the patients, especially who are over 40 yr of age, throughout the high dose tacrolimus therapy.

Association between Type 2 Diabetes and Genetic Variations in Uncoupling Protein 2, beta3-Adrenergic Receptor, and Peroxisome Proliferator-Activated Receptor gamma in Korean.: Min Kyong Moon, Young Min Cho, Hye Seung Jung, Tae Yong Kim, Yun Yong Lee, Joong Yeol Park, Ki Up Lee, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, Hyoung Doo Shin; Korean Diabetes J. 2002;26(6):469-480. Published online December 1, 2002

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Abstract PDF: BACKGROUND
Type 2 diabetes mellitus is a multifactorial disease influenced by numerous genetic and environmental factors. The uncoupling proteins, 2 (UCP2), beta3-adrenergic receptor ADRB3, and peroxisome proliferator-activated receptor gamma PPAR gamma, are genes involved in energy expenditure and fatty acid metabolisms, ans are therefore regarded as candidate genes for type 2 diabetes. In this study, we examined whether the known polymorphisms of UCP2, ADRB3 and PPAR gamma are associated with type 2 diabetes in the Korean population. METHODS: We studied 516 type 2 diabetic patients and 147 control subjects. The enrollment criteria for the control subjects were as follows; age > 60 years, no family history of diabetes in their first-degree relatives, a fasting plasma glucose (FPG) < 6.1 mmol/L, and a HbA1C < 5.8%. Height, weight, waist and hip circumference, FPG, 2 hour-plasma glucose after 75g-glucose load (2h-PG), blood pressure, lipid profile, and fasting insulin level were measured. The Ala55Val polymorphism of the UCP2, Trp64Arg polymorphism of the ADRB3, and Pro12Ala polymorphism of the PPAR gamma were determined by single base extension method. RESULTS: The allele frequency of the Ala55Val variant of the UCP2 tended to be higher in the control subjects than in the type 2 diabetic patients (0.497 vs. 0.456, p=0.064). The allele frequencies of the Trp64Arg polymorphism of the ADRB3, and the Pro12Ala polymorphism of the PPAR gamma, were comparable between the diabetic patients and the control subjects (0.141 vs. 0.152 and 0.033 vs. 0.041, respectively). In the control subjects, the Ala55Val polymorphism of the UCP2 was associated with a significantly lower 2h-PG compared to the wild type (6.0 +/- 0.8 mmol/L vs. 6.6 +/- 0.7 mmol/L, p=0.002). The female control subjects, with the ADRB3 Trp64Arg variant, had a significantly lower triglyceride level than those without the variant (1.36 +/- 0.53 mmol/L vs. 1.74 +/- 0.82 mmol/L, p=0.020). The type 2 diabetic patients, with the ADRB3 Trp64Arg variant showed a significantly lower body mass index (23.6 +/- 2.6 kg/m2vs. 24.6 +/- 3.0 kg/m2, p=0.001). The PPAR gamma Pro12Ala variant, was not associated with any of the features of insulin resistance. The combined genotype of the Val allele of UCP2, Trp allele of ADRB3 and Ala allele of PPAR gamma was less frequent among the type 2 diabetes patients than the control subjects (0.020 vs. 0.056, p=0.039). CONCLUSION: The Ala55Val variant of the UCP2, the Trp64Arg variant of the ADRB3 and the Pro12Ala variant of the PPAR gamma, were not associated with type 2 diabetes in the Korean population. However, the Ala55Val variant of the UCP2 was associated with a lower 2h-PG in the control subjects and the Trp64Arg variant of the ADRB3 was associated with a lower triglyceride level in the female control subjects. Further study may be required to elucidate if the combined genotype of Val allele of UCP2, Trp allele of ADRB3 and Ala allele of PPAR gamma would be protective against type 2 diabetes.

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