Diabetes & Metabolism Journal

Original Articles

Drug/Regimen
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-Young Min, Sungrae Kim; Diabetes Metab J. 2022;46(6):855-865. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0264

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Background
Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice.
Methods
In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled.
Results
Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42.
Conclusion
Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.

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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
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
Lobeglitazone

Reactions Weekly.2023; 1948(1): 262. CrossRef
Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study
Joonsang Yoo, Jimin Jeon, Minyoul Baik, Jinkwon Kim
Cardiovascular Diabetology.2023;[Epub] CrossRef
Lobeglitazone and Its Therapeutic Benefits: A Review
Balamurugan M, Sarumathy S, Robinson R
Cureus.2023;[Epub] CrossRef
Oldies but Goodies: Thiazolidinedione as an Insulin Sensitizer with Cardioprotection
Eun-Hee Cho
Diabetes & Metabolism Journal.2022; 46(6): 827. CrossRef

Clinical Care/Education
Is an Oral Glucose Tolerance Test Still Valid for Diagnosing Diabetes Mellitus?: Dong-Lim Kim, Sun-Doo Kim, Suk Kyeong Kim, Sooyoun Park, Kee-Ho Song; Diabetes Metab J. 2016;40(2):118-128. Published online November 20, 2015; DOI: https://doi.org/10.4093/dmj.2016.40.2.118

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Background

We evaluated the diagnostic rate of diabetes using fasting plasma glucose (FPG), 2-hour plasma glucose (2h PG) after 75 g oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels, and we elucidated the pathophysiologic characteristics and risk factors that give rise to diabetes in patients with prediabetes.

Methods

The data of 236 patients who had the OGTT at Konkuk University Hospital were analyzed. Fasting, 30, and 120 minutes blood glucose levels and insulin levels were measured. The diagnostic rate of diabetes was assessed using FPG, 2h PG, and HbA1c levels. The clinical data and insulin resistance and secretion evaluations were compared using indexes according to the fasting glucose level.

Results

Among 236 subjects, 97 (41.1%) were diabetics and 102 (43.2%) were prediabetics. The rate of diabetes diagnosis by one of the individual criteria was 56.7%, 53.6%, and 84.5% for FPG, HbA1c, and 2h PG, respectively. When two criteria were used to diagnose diabetes, 72.2% of the diabetic patients were identified by FPG and HbA1c, while 100% were identified by FPG and 2h PG, and 91.7% were identified by 2h PG and HbA1c. The HbA1c cut-off value for 2h PG ≥200 mg/dL was 6.1%, and the FPG cut-off value was 115 mg/dL. In impaired fasting glucose subjects, the HbA1c level, Matsuda index, and insulinogenic index were associated with risk of occurrence of overt diabetes (P<0.01).

Conclusion

This study suggests that performing additional OGTT for patients with FPG ≥110 mg/dL or HbA1c ≥6.1% is helpful to reclassify their glucose tolerance status and evaluate their potential for progressing to overt diabetes.

Citations

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The effect of preprandial versus postprandial physical activity on glycaemia: Meta-analysis of human intervention studies
Romy Slebe, Eva Wenker, Linda J. Schoonmade, Emma J. Bouman, Denis P. Blondin, David J.T. Campbell, André C. Carpentier, Joris Hoeks, Parminder Raina, Patrick Schrauwen, Mireille J. Serlie, Dirk Jan Stenvers, Renée de Mutsert, Joline W.J. Beulens, Femke R
Diabetes Research and Clinical Practice.2024; 210: 111638. CrossRef
Dysglycaemia prediction using readily available clinical, anthropometric, and biochemical measurements
R. Guizar-Heredia, M. Guevara-Cruz, M. Aguilar-López, L.E. González-Salazar, I. Medina-Vera, L. Arteaga-Sánchez, E. Pichardo-Ontiveros, A.E. Serralde-Zúñiga, A. Diaz-Villaseñor, A. Ávila-Nava, N. Torres, A.R. Tovar
Clinical Nutrition Open Science.2024; 55: 91. CrossRef
Dichotomy in the Impact of Elevated Maternal Glucose Levels on Neonatal Epigenome
Ives Yubin Lim, Xinyi Lin, Ai Ling Teh, Yonghui Wu, Li Chen, Menglan He, Shiao-Yng Chan, Julia L MacIsaac, Jerry K Y Chan, Kok Hian Tan, Mary Foong Fong Chong, Michael S Kobor, Keith M Godfrey, Michael J Meaney, Yung Seng Lee, Johan G Eriksson, Peter D Gl
The Journal of Clinical Endocrinology & Metabolism.2022; 107(3): e1277. CrossRef
Imaging evaluation of the pancreas in diabetic patients
Ni Zeng, Yi Wang, Yue Cheng, Zixing Huang, Bin Song
Abdominal Radiology.2022; 47(2): 715. CrossRef
The Impact of Financial Incentives on Behavior and Self-Management of Uncontrolled Type 2 Diabetes: Pre- and Post-Quasiexperimental Study
Dalal Abdulaziz Al Kathiry, Fatima Al Slail, Khaled Al-Surimi, Raghib Abusaris
Global Journal on Quality and Safety in Healthcare.2021; 4(3): 88. CrossRef
Practice Patterns in the Acceptance of Medically Complex Living Kidney Donors with Obesity, Hypertension, Family History of Kidney Disease, or Donor-Recipient Age Discrepancy
Ziad Arabi, Muhammad Bukhari, Abdullah Hamad, Abdulrahman Altheaby, Saleh Kaysi
Avicenna Journal of Medicine.2021; 11(04): 172. CrossRef
Secretagogin is Related to Insulin Secretion but Unrelated to Gestational Diabetes Mellitus Status in Pregnancy
Carola Deischinger, Jürgen Harreiter, Karoline Leitner, Dagmar Bancher-Todesca, Sabina Baumgartner-Parzer, Alexandra Kautzky-Willer
Journal of Clinical Medicine.2020; 9(7): 2277. CrossRef
Hypoglycemic activity of extracts of Chamaecyparis obtusa var. formosana leaf in rats with hyperglycemia induced by high-fat diets and streptozotocin
Chia-Yun Hsu, Gong-Min Lin, Shang-Tzen Chang
Journal of Traditional and Complementary Medicine.2020; 10(4): 389. CrossRef
Optimal fasting plasma glucose and haemoglobin A1c levels for screening of prediabetes and diabetes according to 2‐hour plasma glucose in a high‐risk population: The Korean Diabetes Prevention Study
Seon‐Ah Cha, Suk Chon, Jae‐Seung Yun, Sang Youl Rhee, Sun‐Young Lim, Kun‐Ho Yoon, Yu‐Bae Ahn, Seung‐Hyun Ko, Jeong‐Taek Woo, Jin‐Hee Lee
Diabetes/Metabolism Research and Reviews.2020;[Epub] CrossRef
Prediction of type 2 diabetes mellitus using fasting plasma glucose and HbA1c levels among individuals with impaired fasting plasma glucose: a cross-sectional study in Thailand
Tullaya Sitasuwan, Raweewan Lertwattanarak
BMJ Open.2020; 10(11): e041269. CrossRef
The effect of oral glucose tolerance testing on changes in arterial stiffness and blood pressure in elderly women with hypertension and relationships between the stage of diabetes and physical fitness levels
Jaesong Lee, Wonil Park, Eunsook Sung, Bokbeom Kim, Nahyun Kim, Saejong Park, Chulho Shin, Jonghoon Park
Physical Activity and Nutrition.2020; 24(4): 34. CrossRef
From Pre-Diabetes to Diabetes: Diagnosis, Treatments and Translational Research
Radia Khan, Zoey Chua, Jia Tan, Yingying Yang, Zehuan Liao, Yan Zhao
Medicina.2019; 55(9): 546. CrossRef
Molecular imaging of β-cells: diabetes and beyond
Weijun Wei, Emily B. Ehlerding, Xiaoli Lan, Quan-Yong Luo, Weibo Cai
Advanced Drug Delivery Reviews.2019; 139: 16. CrossRef
HbA1c Cutoff for Prediabetes and Diabetes Based on Oral Glucose Tolerance Test in Obese Children and Adolescents
Hyo-Kyoung Nam, Won Kyoung Cho, Jae Hyun Kim, Young-Jun Rhie, Sochung Chung, Kee-Hyoung Lee, Byung-Kyu Suh
Journal of Korean Medical Science.2018;[Epub] CrossRef
Detection of glucose metabolism disorders in coronary patients enrolled in cardiac rehabilitation: Is glycated haemoglobin useful? Data from the prospective REHABDIAB study
Sopio Tatulashvili, Bénédicte Patois-Vergès, Amandine Nguyen, Marie-Cécile Blonde, Bruno Vergès
European Journal of Preventive Cardiology.2018; 25(5): 464. CrossRef
Imaging in pancreatic disease
Julien Dimastromatteo, Teresa Brentnall, Kimberly A. Kelly
Nature Reviews Gastroenterology & Hepatology.2017; 14(2): 97. CrossRef

The Association between Midnight Salivary Cortisol and Metabolic Syndrome in Korean Adults: Yun-Mi Jang, Eun Jung Lee, Dong Lim Kim, Suk Kyeong Kim, Kee-Ho Song; Diabetes Metab J. 2012;36(3):245-250. Published online June 14, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.3.245

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Background

The common characteristics of metabolic syndrome (MetS) and Cushing's syndrome suggest that excess cortisol may be involved in the pathogenesis of MetS. Salivary cortisol measurements are simple and can be surrogates for plasma free cortisol, which is the most biologically active form. We evaluated the association between levels of midnight salivary cortisol and MetS in Korean adults.

Methods

A total of 46 subjects, aged 20 to 70 years, who visited the Health Care Center at Konkuk University Hospital from August 2008 to August 2009 were enrolled. We compared the levels of midnight salivary cortisol in subjects with MetS with those in subjects without MetS. We analyzed the associations between midnight salivary cortisol levels and components of MetS.

Results

Midnight salivary cortisol levels were higher in the MetS group (70±42.4 ng/dL, n=12) than that in the group without MetS (48.1±36.8 ng/dL, n=34) (P=0.001). Positive correlations were observed between midnight salivary cortisol levels and waist circumference, fasting blood glucose, and homeostasis model assessment of insulin resistance. The risk for MetS was significantly higher in subjects with midnight salivary cortisol levels ≥100 ng/dL than in those with levels <50 ng/dL (odds ratio, 5.9; 95% confidence interval, 2.35 to 36.4).

Conclusion

The results showed a positive correlation between midnight salivary cortisol levels and MetS, suggesting that hypercortisolism may be related to MetS.

Citations

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Evaluation of salivary endothelin-1 as a biomarker for oral cancer and precancer
Sumaiya Irfan, Noorin Zaidi, Kshama Tiwari, Nirupma Lal, Anand Narayan Srivastava, Shivangi Singh
Journal of Cancer Research and Therapeutics.2023;[Epub] CrossRef
Association of primary allostatic load mediators and metabolic syndrome (MetS): A systematic review
Francis Osei, Andrea Block, Pia-Maria Wippert
Frontiers in Endocrinology.2022;[Epub] CrossRef
Salivary cortisol levels during Ramadan fasting in hydrocortisone-treated secondary adrenal insufficiency patients
Melika Chihaoui, Wiem Madhi, Meriem Yazidi, Bessem Hammami, Ibtissem Oueslati, Nadia Khessairi, Wafa Grira, Amina Bibi, Moncef Feki, Fatma Chaker
Endocrine.2020; 70(2): 404. CrossRef
Basal cortisol levels and metabolic syndrome: A systematic review and meta-analysis of observational studies
Anderson Garcez, Heloísa Marquardt Leite, Elisabete Weiderpass, Vera Maria Vieira Paniz, Guilherme Watte, Raquel Canuto, Maria Teresa Anselmo Olinto
Psychoneuroendocrinology.2018; 95: 50. CrossRef
Is salivary gland function altered in noninsulin-dependent diabetes mellitus and obesity–insulin resistance?
Jitjiroj Ittichaicharoen, Nipon Chattipakorn, Siriporn C. Chattipakorn
Archives of Oral Biology.2016; 64: 61. CrossRef
The Role of Cortisol in the Pathogenesis of the Metabolic Syndrome
In-Kyung Jeong
Diabetes & Metabolism Journal.2012; 36(3): 207. CrossRef

Case Reports

Hypoglycemia due to Focal Nesidioblastosis in a Patient with Type 2 Diabetes Mellitus.: Eun Jung Lee, Kee Ho Song, Suk Kyeong Kim, Seong Hwan Chang, Dong Lim Kim; Korean Diabetes J. 2009;33(3):251-256. Published online June 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.3.251

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Abstract PDF: We report a 45-year-old man with type 2 diabetes who presented with recurrent hypoglycemia. Biochemical and imagingstudies did not show any mass-like lesion in the pancreas, so prednisolone and diazoxide were administered for the treatment of hypoglycemia. However, the hypoglycemia persisted during and after the medical treatment. A selective arterial calcium stimulation test was performed and revealed a suspicious lesion at the head of the pancreas. The patient underwent enucleation of the pancreas head lesion. The lesion was confirmed histologically to be focal nesidioblastosis and surgical resection was successfully performed. The patient showed no hypoglycemic symptoms postoperatively.

A Case of Ketosis-Prone Type 2 Diabetes Mellitus.: Dong Lim Kim, Suk Kyeong Kim, Kee Ho Song; Korean Diabetes J. 2007;31(3):293-296. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.293

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Abstract PDF

Ketosis-prone type 2 diabetes (KPD) has been characterized as diabetes with severe insulin deficiency at diagnosis associated with ketosis or ketoacidosis without a precipitating cause. Improvement in beta-cell function and insulin sensitivity by aggressive diabetic management could allow discontinuation of insulin therapy within a few month of therapy. These subjects are usually obese, have a strong family history of diabetes, absence of beta-cell autoimmune markers and lack of human leukocyte antigen genetic association. This clinical presentation has been reported primarily in African and African Americans, but rare in Asian and white person. We recently experienced a case of KPD in Korea and present it with literature review.

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A Case of Autoantibody-Positive Ketosis-Prone Diabetes Mellitus
Bora Yoon, Gyuri Kim, Jae Hyun Bae, Yu Jung Yun, Yong Ho Lee, Byung Wan Lee, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee, Eun Seok Kang
The Journal of Korean Diabetes.2016; 17(1): 60. CrossRef

Original Articles

Effects of Lovastatin on Free Fatty Acid Oxidation in Cultured L6 Rat Skeletal Muscle Cells.: Dong Lim Kim, Kee Ho Song, Hae Rim Kim, Suk Kyeong Kim; Korean Diabetes J. 2007;31(3):230-235. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.230

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Abstract PDF

BACKGROUND
Recent clinical studies suggest that statins improve insulin resistance and glucose metabolism in patients with metabolic syndrome and type 2 diabetes. To evaluate the possible mechanism of this action, we measured free fatty acid oxidation in cultured L6 rat skeletal muscle cell line. METHODS: Cultured L6 myotubes were treated with or without lovastatin (1, 5, 20 micrometer) for 24 hours or 48 hours and palmitate oxidation was measured. We also measured protein concentration of the cells. RESULTS: Lovastain increased palmitate oxidation in dose and time dependent manner in L6 myotubes (24 hr; 1 micrometer 119.2 +/- 11.9% of control, 5 micrometer 140.9 +/- 8.1%, 20 micrometer 150 +/- 5%, P = 0.05 vs control, respectively, 48 hr 1 micrometer 120.9 +/- 14.5%, 5 micrometer 176.6 +/- 28.2%, 20 micrometer 196.0 +/- 19.9%, P < 0.01 vs control, respectively). However, lovastatin decreased total cellular protein (24 hr: 1 micrometer 89.2 +/- 6.1% of control, 5 micrometer 79.3 +/- 7.6%, 20 micrometer 65.4 +/- 4.2%, P = 0.05 vs control, respectively, 48 hr: 1 micrometer 81.7 +/- 5.1%, 5 micrometer 58.6 +/- 11.9%, 20 micrometer 48.1 +/- 6.9%, P < 0.01 vs control, respectively). CONCLUSION: Lovastatin increased skeletal muscle free fatty acid oxidation in L6 rat skeletal muscle cells. This would be one of the mechanisms which lovastatin improves insulin resistance.

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Characterization and Mechanisms of Action of Avocado Extract Enriched in Mannoheptulose as a Candidate Calorie Restriction Mimetic
Donald K. Ingram, Paul J. Pistell, Zhong Q. Wang, Yongmei Yu, Stefan Massimino, Gary M. Davenport, Michael Hayek, George S. Roth
Journal of Agricultural and Food Chemistry.2021; 69(26): 7367. CrossRef

Fetal Protein Deficiency Causes Long Term Changes in Mitochondrial DNA Content of Liver and Muscle in Female Sprague-Dawley Rats.: Suk Kyeong Kim, Min Seon Kim, Youn Young Kim, Do Joon Park, Kyong Soo Park, Ki Up Lee, Hong Kyu Lee; Korean Diabetes J. 2003;27(2):115-122. Published online April 1, 2003

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Abstract PDF: BACKGROUND
Epidemiological data suggest a strong association between low birth weight and the increased risk of metabolic syndrome, including type 2 diabetes, hypertension and cardiovascular disease, in adult life. However, the underlying mechanisms are largely unknown. In our previous study, the mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes was decreased in patients with type 2 diabetes and insulin resistance. To test the hypothesis that mitochondrial changes may serve as a link between fetal under nutrition and insulin resistance in later life, the effects of fetal protein malnutrition on the mitochondria of the liver and skeletal muscle, the main sites of insulin action in adulthood, were investigated. METHODS: Eight-week old female rats were divided into 2 groups and fed on either a control diet (casein 180 g/kg diet) (n=5) or a low protein diet (casein 80 g/kg diet) (n=7) for 15 days prior to mating. They were mated with 10 week-old male Sprague Dawley rats that had been fed on the control diet. The female offspring, born to the mothers fed the low protein diet, were randomly divided into 2 groups 4 weeks after birth, and weaned on either the low protein (low protein group, n=48) or control diet (resuscitated group, n=48). As a control group, the offspring born to the mothers fed the control diet were weaned on the control diet (n=48). The animals in each group were again randomly divided into 4 groups, and sacrificed at 5, 10, 15 and 20 weeks of age, respectively (n=12 per group). The body weight, liver and muscle mtDNA content were measured at weeks 5, 10, 15 and 20. RESULTS: The mtDNA contents of the liver and skeletal muscle were reduced in fetal malnourished adult rats, and were not restored to normal levels even when proper nutrition was supplied after weaning. CONCLUSION: Our findings indicate that under nutrition in early life causes long lasting changes in the mitochondria DNA content of the liver and muscles, which may contribute to the development of insulin resistance in later life.

Oxidative Stress and Antioxidative Defense System in Offspring of Protein-Malnourished Rats.: Eun Young Cho, Hyeong Kyu Park, Hyeon Jeong Jeon, Suk Kyeong Kim, Kyong Soo Park, Chong Ho Lee, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2001;25(3):190-199. Published online June 1, 2001

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Abstract PDF: BACKGROUND
Free radical-mediated oxidative damage has been implicated in a variety of pathological processes such as diabetes mellitus, aging and atherosclerosis. The susceptibility of a given organism to oxidative damage is influenced by the overall balance between the degree of oxidative stress and antioxidative capabilities. Nutrition plays an important role in determining the cellular antioxidative defense mechanism. Thus, the aim of this study is to investigate the effects of fetal protein malnutrition on oxidative stress and antioxidative capabilities. METHOD: Rats were fed a low-protein (8% casein) diet throughout pregnancy and lactation. Male offspring were weaned onto either a control (18% casein) diet (group 2) or a low-protein diet (group 3). Offspring from rats fed a control diet were weaned onto a control diet (group 1). The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and the concentration of thiobarbituric acid- reactive substances (TBARS) were determined at 10 and 15 wk in liver and skeletal muscle from offspring. RESULTS: SOD activities of liver in group 3 were significantly lower than those in group 1 at 10 wk (4.14+/-0.65 U/mg protein, 9.09+/-0.85 U/mg protein) and 15 wk (4.18+/-0.58 U/mg protein, 7.63+/-0.74 U/mg protein), respectively. But SOD activities of skeletal muscle were not different between groups. Whilst GPx activities of liver were not different at 10 wk, GPx activities in group 2 (1.80+/-0.16 U/mg protein) were significant higher than those in group 1 (1.24+/-0.15 U/mg protein) at 15 wk. GPx activities of skeletal muscle were not different between groups. The TBARS concentrations in liver or skeletal muscle were not different between groups at 10 and 15 wk. There was a significant negative correlation between SOD activities and TBARS concentrations in liver (r=-0.359). CONCLUSION: In offspring of rats fed a low-protein diet throughout pregnancy and lactation, the antioxidant enzyme activities were significantly decreased, compared with offspring of rats fed a control diet. These alterations were not fully restored in low-protein offspring even when weaned onto a control diet. These results suggest that fetal protein malnutrition impair the antioxidative defense system.

The Prevalence of the Mitochondrial DNA 16189 Variant in Korean Adults and Its Association with Insulin Resistance.: Seong Yeun Kim, Hang Kyu Lee, Do Joon Park, Bo Yeon Cho, Suk Kyeong Kim, Geon Sang Park, Jae Hyun Kim, Kyong Soo Park, Bong Sun Kang; Korean Diabetes J. 1999;23(3):299-306. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Mutations in mitochondrial DNA (mtDNA) are of potential importance in the pathogenesis of diabetes mellitus. MtDNA 3243 mutation (G->A) is famous and associated with insulin secretory defect, but it is found in only 0.52% of type 2 diabetes mellitus and it can explain only a small proportion of the patients with diabetes mellitus. Recently Poulton et al. showed that the 16189 variant (T C transition) in mtDNA was associated with insulin resistance in Caucasians. They showed that the prevalence of the 16189 variant in the American was 11% and the people with the 16189 variant had higher fasting insulin and HOMA insulin resistance than the people without the 16l89 variant. In this study, we investigated the prevalence of the 161S9 variant in Korean adults and its association with insulin resistance. METHODS: We utilized the stored blood samples from community-based diabetes survey conducted in Yonchon County, Korea in 1993. We randomly selected 160 samples. We extracted the DNA from peripheral blood samples and examined the 16189 variant by PCR and restrictive enzyme digestion. We measured BMI, waist-hip ratio, blood pressure, fasting glucose, postprandial 2 hour glucose, fasting insulin, total cholesterol, triglyceride and HDL- cholesterol. HOMA insulin resistance and beta-cell function were calculated from fasting glucose and fasting insulin. RESULTS: The prevalence of the 16189 variant in Korean adults was 28.8% (46/160), higher than in the American, but the same as in the Japanese. The subjects with the 16189 variant had higher fasting glucose and BMI than the subjects without the 16189 variant, but fasting insulin, HOMA insulin resistance, beta-cell function, cholesterol and blood pressure were not different between the two groups. CONCLUSION: The prevalence of the 16189 variant in the Korean is higher than in the Caucasian but the same as in the Japanese. Our results support that a frequent mitochondrial variant may contribute to the phenotype related to insulin resistance. However, further detailed studies must be made in a large number of patients.

NcoI Restriction Fragment Length Polymorphism(RFLP) on the TNF-beta gene in Korean Patients with Type 1(insulin-dependent) Diabetes Mellitus.: Suk Kyeong Kim, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, Hun Ki Min, Tae Gun O; Korean Diabetes J. 1998;22(2):155-163. Published online January 1, 2001

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Abstract PDF: BACKGROUND
To investigate whether a TNF-g gene polymorphism is associated with the development of insulin-dependent diabetes mellitus, we analyzed the TNF-g gene polymorphism with restriction enzyme Ncol in 38 Korean patients with insulin -dependent diabetes mellitus(IDDM) and in 150 healthy controls. METHODS: Genomic DNA was extracted from white blood cells, and amplified by polymerase chain reaction(PCR) on 735 base pairs fragment of TNF-g gene with NcoI polymorpnic site. 735 bp PCR product was digested with NcoI restriction endonuclease, then analyzed by agarose gel electrophoresis to detect the NcoI restriction fragment length polymorphism(RFLP). The TNF-g alleles were divided into two types according to the electrophoresis patterns. TNF-b*1 allele, which contains the Ncol restriction site(CCATGG), should be digested 539 bp and 196 bp fragments. On the other hand, TNF-g*2 allele, which lacks the restriction site, only showed 735 bp fragment. RESULTS: Six out of 38(15.8%) IDDM patients were homozygous for the TNF-b*1 allele, 11(28.9%) were homozygous for the TNF-b*2 alleie, and 21 (55.3%) were TNF-b*1/*2 heterozygous compared to 21.7%, 30.7% and 49.3%(p=0.83), respectively, in control subjects. CONCLUSION: The TNF-b gene polymorphism was not associated with insulin-dependent diabetes mellitus in Korean subjects.

Hyperfibrinogenemia as an Important Risk Factor for Microvascular Complications in NIDDM Patients.: Suk Kyeong Kim, Hyeong Kyu Park, Sun Wook Kim, Do Joon Park, Chan Soo Shin, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; Korean Diabetes J. 1997;21(4):406-413. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Abundant evidences have accumulated to suggest that atherosclerosis is accelerated in both type I and type Il diabetes but, traditional risk factors(hyperlipidemia, hypertension, smoking, age, obesity) do not account fully for the increased prevalence and severity of vascular diseases in diabetes. In this study, we examined the relationship of plasma fibrinogen to microvascular complications in NIDDM patients METHODS: In this cross-sectional study, 104 NIDDM patients were chosen from subjects who were attending the metabolic ward of Seoul National University Hospital. None of them were smokers, nor had any clinical evidences of acute infections, cancers or liver diseases. Arnong 104 patients, 55 patients (male 26, fernale 29) had no evidence of microvascular complications and 49(male 30, female 19) had one or moe microvascular complications. Their mean age(55.7+11.6 and 57.2+8.9 years old) and BMI (23.34+2.98 kg/m and 23.74+3.41 kg/m) were similar between two groups. This study defined microvascular complications as follows: 1) retinopathy classified based on fundoscopic and fluorescein angiographic assessmeot to background and proliferative, 2) nephropathy defined by 24 hour urine protein over 500mg, and 3) pheripheral neuropathy assessed by symptoms or NCV. RESULTS: 1) Clinically, there was no differences between two groups with respect to diastolic BP, C-peptide, HbA1c, and triglyceride level. However statistically significant differences were noted in systolic blood pressure, and total and LDL-cholesterol. Also mean fibrinogen level was more elevated significantly in diabetic patients with microvascular complications than those without microvascular complications. 2) Univariate analysis shows significant correlations between fibrinogen and the other variables such as duration of diabetes, total cholesterol level and systolic blood pressure. 3) However, fibrinogen concentration was higher in NIDDM patients with microvascuiar complications regardless of duration of diabetes, hypertension and HbA1c in multivariate logisric regression analysis (P=0.010). Conclusions: These results indicated that hyperfibrinogenemia were observed in NIDDM patient with microvascular complications regardless of duration of diabetes, systolic BP, and total cholesterol. Therefore our study suggests that hyperfibrogenemia may be one of the important missing links in the pathogenesis of diabetic microvascular diseases.

Mitochondrial DNA point mutations in Korean NIDDM patients.: Suk Kyeong Kim, Kyong Soo Park, Chan Soo Shin, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh; Korean Diabetes J. 1997;21(2):147-155. Published online January 1, 2001

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Abstract PDF: BACKGROUND
There are a few genes with proven potential for causing some form of NIDDM, These include the insulin gene, the insulin receptor gene, a gene linked to the adenosine deaminase gene on chrornosome 20, and the glucokinase gene. Recently, an A to G transition at position 3243 in transfer ribonucleic acid ""' ' was reported in maternally inherited NIDDM patients in Japan, it was reported that approximately 1% of diabetes patients have the 3243 bp point mutation. In this study we examined the positive rate and clinical characteristics of Korean NIDDM patients with mitochondrial DNA point mutation. METHODS: We screened randomly selected 433 NIDDM patients (rnale 221, female 212) from the diabetes clinic of Seoul National University Hospital regardless of age of onset, family history of diabetes, mode of' therapy, or any other clinical characteristics. Genomic DNA was extracted from pheripheral lymphocytes. To detect the 3243 bp mutation, PCR was carried out using mtDNA primers(2928-2947, 3558-3539) and then, PCR products were electro-phoresed on a 2%: agarose gel after digestion with the restriction endonuclease Apa-I. When electrophoretic results showed two or three bands, we confirmed mtl)NA 3243 bp point rnutation by DNA sequencing. RESULTS: Of the 433 Korean NIDDM patients, 5 patiients had mtDNA point mutation digested by restriction endonuclease Apa I. Only two patients (OA6%) had heteroplasmic point mutation at nucleo-tide 3243. The remaining three patients(0.69%) with homoplasmic point mutation at nt 3426 were inciden-tally discovered during procedure in detecting 3243 bp point mutation. This 3426 point rnutation had the same adenine to guanine point mutation as 3243 point mutation digested by Apa I and therefore was confused with 3243 point mutation by RFLP method. Two patients with 3243 points mutation, aged 39 and 32 years, BMI 17.0 and 14.4(kg/m), had neither hearing impairrnent nor family history of diabetes. They required insulin for the control of their hyperglycemia and their C-peptide levels less than 1.Ong/mL showed insulin dependent tendency. On the contrary, three patients with 3426 bp point mutation, aged 71, 70, and 62 years, BMI 28.0, 23.0, and 22.6 (kg/m2 ), showed their C-peptide levels 5.4ng/mL and 3.%g/mL and insulin resistant diabetes mellitus. CONCLUSION: Two kinds of point mutation were found in the mtDNA at position nt 3243 and nt 3426, and their incidence were 0.46%(2/433) and 0.69% (3/433) respectively. 3243 point mutation was associated with insulin deficient diabetes mellitus whereas 3426 point mutation insulin resistant diabetes mellitus. 3426 point mutation has the same adenine to guanine transition as 3243 point mutation restricted by Apa I and so, DNA sequencing is warranted to differentiate with 3426 from 3243 point mutation.

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