Diabetes & Metabolism Journal

Original Articles

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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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

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.2024; 44(4): 799. CrossRef
The progress of clinical research on the detection of 1,5-anhydroglucitol in diabetes and its complications
Huijuan Xu, Junhua Pan, Qiu Chen
Frontiers in Endocrinology.2024;[Epub] CrossRef
Glycation and Glucose Variability in Subjects with Type 1 Diabetes
V. V. Klimontov, D. M. Bulumbaeva, J. F. Semenova
Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry.2024; 18(1): 59. CrossRef
The clinical potential of 1,5-anhydroglucitol as biomarker in diabetes mellitus
Haiying Xu, Renyin Chen, Xiaoli Hou, Na Li, Yanwei Han, Shaoping Ji
Frontiers in Endocrinology.2024;[Epub] CrossRef
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
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

The Glycated Albumin to Glycated Hemoglobin Ratio Might Not Be Associated with Carotid Atherosclerosis in Patients with Type 1 Diabetes: Wonjin Kim, Kwang Joon Kim, Byung-Wan Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee; Diabetes Metab J. 2014;38(6):456-463. Published online December 15, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.6.456

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Abstract PDF PubReader

Background

The ratio of glycated albumin to glycated hemoglobin (GA/A1c) is known to be elevated in subjects with type 2 diabetes mellitus (T2DM) who had decreased insulin secretion. Additionally, the carotid intima media thickness (IMT) is greater in T2DM patients with higher GA/A1c ratios. We investigated whether increased GA/A1c ratio and IMT are also associated in type 1 diabetes mellitus (T1DM), which is characterized by lack of insulin secretory capacity.

Methods

In this cross-sectional study, we recruited 81 T1DM patients (33 men, 48 women; mean age 44.1±13.0 years) who underwent carotid IMT, GA, and HbA1c measurements.

Results

The mean GA/A1c ratio was 2.90. Based on these results, we classified the subjects into two groups: group I (GA/A1c ratio <2.90, n=36) and group II (GA/A1c ratio ≥2.90, n=45). Compared with group I, the body mass indexes (BMIs), waist circumferences, and IMTs were lower in group II. GA/A1c ratio was negatively correlated with BMI, urine albumin to creatinine ratio (P<0.001 for both), and both the mean and maximal IMT (P=0.001, both). However, after adjusting the confounding factors, we observed that IMT was no longer associated with GA/A1c ratio.

Conclusion

In contrast to T2DM, IMT was not significantly related to GA/A1c ratio in the subjects with T1DM. This suggests that the correlations between GA/A1c ratio and the parameters known to be associated with atherosclerosis in T2DM could be manifested differently in T1DM. Further studies are needed to investigate these relationships in T1DM.

Citations

Citations to this article as recorded by

High glycated albumin is associated with early neurological deterioration in patients with acute ischemic stroke
Ki-Woong Nam, Jung Hoon Han, Chi Kyung Kim, Hyung-Min Kwon, Yong-Seok Lee, Kyungmi Oh, Keon-Joo Lee, Byeongsu Park
BMC Neurology.2024;[Epub] CrossRef
Glycated Albumin and Glycated Albumin/HbA1c Predict the Progression of Coronavirus Disease 2019 from Mild to Severe Disease in Korean Patients with Type 2 Diabetes
Jeongseon Yoo, Youngah Choi, Shin Ae Park, Ji Yeon Seo, Chul Woo Ahn, Jaehyun Han
Journal of Clinical Medicine.2022; 11(9): 2327. CrossRef
Variability in glycated albumin levels predicts the progression of diabetic nephropathy
Su Bin Park, Sang Soo Kim, In Joo Kim, Yoon Jeong Nam, Kang Hee Ahn, Jong Ho Kim, Yun Kyung Jeon, Bo Hyun Kim, Sang Heon Song, Ihm Soo Kwak, Eun Kyung Lee, Yong Ki Kim
Journal of Diabetes and its Complications.2017; 31(6): 1041. CrossRef
Significant liver fibrosis assessed using liver transient elastography is independently associated with low bone mineral density in patients with non-alcoholic fatty liver disease
Gyuri Kim, Kwang Joon Kim, Yumie Rhee, Sung-Kil Lim, Salvatore Petta
PLOS ONE.2017; 12(7): e0182202. CrossRef
Determinants of Preclinical Atherosclerosis Are Different in Type 1 and Type 2 Diabetic Women
P. PIŤHOVÁ, K. ŠTECHOVÁ, J. PIŤHA, V. LÁNSKÁ, M. KVAPIL
Physiological Research.2016; : 219. CrossRef
Characteristics Predictive for a Successful Switch from Insulin Analogue Therapy to Oral Hypoglycemic Agents in Patients with Type 2 Diabetes
Gyuri Kim, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Byung-Wan Lee
Yonsei Medical Journal.2016; 57(6): 1395. CrossRef
Visceral adiposity is associated with altered myocardial glucose uptake measured by 18FDG-PET in 346 subjects with normal glucose tolerance, prediabetes, and type 2 diabetes
Gyuri Kim, Kwanhyeong Jo, Kwang Joon Kim, Yong-ho Lee, Eugene Han, Hye-jin Yoon, Hye Jin Wang, Eun Seok Kang, Mijin Yun
Cardiovascular Diabetology.2015;[Epub] CrossRef
Glycated albumin and the risk of micro- and macrovascular complications in subjects with Type 1 Diabetes
Hye-jin Yoon, Yong-ho Lee, So Ra Kim, Tyler Hyungtaek Rim, Eun Young Lee, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Byung-Wan Lee
Cardiovascular Diabetology.2015;[Epub] CrossRef
Comparison of Candidate Pairs of Hydrolytic Enzymes for Spectrophotometric-dual-enzyme-simultaneous-assay
Hongbo Liu, Mei Yuan, Xiaolan Yang, Xiaolei Hu, Juan Liao, Jizheng Dang, Yanling Xie, Jun Pu, Yuanli Li, Chang-Guo Zhan, Fei Liao
Analytical Sciences.2015; 31(5): 421. CrossRef
Glycated Albumin Levels in Patients with Type 2 Diabetes Increase Relative to HbA1cwith Time
Hye-jin Yoon, Yong-ho Lee, Kwang Joon Kim, So Ra Kim, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Byung-Wan Lee
BioMed Research International.2015; 2015: 1. CrossRef
Association of hemoglobin A1c and glycated albumin with carotid atherosclerosis in community-dwelling Japanese subjects: the Hisayama Study
Naoko Mukai, Toshiharu Ninomiya, Jun Hata, Yoichiro Hirakawa, Fumie Ikeda, Masayo Fukuhara, Taeko Hotta, Masafumi Koga, Udai Nakamura, Dongchon Kang, Takanari Kitazono, Yutaka Kiyohara
Cardiovascular Diabetology.2015;[Epub] CrossRef

The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes: Eun Yeong Choe, Yongin Cho, Younjeong Choi, Yujung Yun, Hye Jin Wang, Obin Kwon, Byung-Wan Lee, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee, Eun Seok Kang; Diabetes Metab J. 2014;38(3):211-219. Published online June 17, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.3.211

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Abstract PDF Supplementary Material PubReader

Background

We evaluated the effects of two dipeptidyl peptidase-4 (DPP-4) inhibitors, sitagliptin and vildagliptin, on metabolic parameters in patients with type 2 diabetes mellitus.

Methods

A total of 170 type 2 diabetes patients treated with sitagliptin or vildagliptin for more than 24 weeks were selected. The patients were separated into two groups, sitagliptin (100 mg once daily, n=93) and vildagliptin (50 mg twice daily, n=77). We compared the effect of each DPP-4 inhibitor on metabolic parameters, including the fasting plasma glucose (FPG), postprandial glucose (PPG), glycated hemoglobin (HbA1c), and glycated albumin (GA) levels, and lipid parameters at baseline and after 24 weeks of treatment.

Results

The HbA1c, FPG, and GA levels were similar between the two groups at baseline, but the sitagliptin group displayed a higher PPG level (P=0.03). After 24 weeks of treatment, all of the glucose-related parameters were significantly decreased in both groups (P=0.001). The levels of total cholesterol and triglycerides were only reduced in the vildagliptin group (P=0.001), although the sitagliptin group received a larger quantity of statins than the vildagliptin group (P=0.002).The mean change in the glucose- and lipid-related parameters after 24 weeks of treatment were not significantly different between the two groups (P=not significant). Neither sitagliptin nor vildagliptin treatment was associated with a reduction in the high sensitive C-reactive protein level (P=0.714).

Conclusion

Vildagliptin and sitagliptin exert a similar effect on metabolic parameters, but vildagliptin exerts a more potent beneficial effect on lipid parameters.

Citations

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Insulin Tregopil: An Ultra-Fast Oral Recombinant Human Insulin Analog: Preclinical and Clinical Development in Diabetes Mellitus
Shashank Joshi, Vathsala Jayanth, Subramanian Loganathan, Vasan K. Sambandamurthy, Sandeep N. Athalye
Drugs.2023; 83(13): 1161. CrossRef
Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study
Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin, Jeong Mi Kim, Min Hee Jang, Kyung Ae Lee, Ju Hyung Lee, Seung Min Chung, Young Sang Lyu, Jin Hwa Kim, Sang Yong Kim, Jung Eun Jang, Tae Nyun Kim, Sung Woo Kim, Eonju Jeon, Nan Hee Cho, Mi-Kyung Ki
Diabetes & Metabolism Journal.2021; 45(5): 675. CrossRef
Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis
Michał Wiciński, Karol Górski, Eryk Wódkiewicz, Maciej Walczak, Magdalena Nowaczewska, Bartosz Malinowski
International Journal of Molecular Sciences.2020; 21(7): 2275. CrossRef
Anti-inflammatory properties of antidiabetic drugs: A “promised land” in the COVID-19 era?
Niki Katsiki, Ele Ferrannini
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Effect of Switching from Linagliptin to Teneligliptin Dipeptidyl Peptidase-4 Inhibitors in Older Patients with Type 2 Diabetes Mellitus

Eugene Han, Minyoung Lee, Yong-ho Lee, Hye Soon Kim, Byung-wan Lee, Bong-Soo Cha, Eun Seok Kang
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 4113. CrossRef
Combined vildagliptin and memantine treatment downregulates expression of amyloid precursor protein, and total and phosphorylated tau in a rat model of combined Alzheimer’s disease and type 2 diabetes
Samar S. Khalaf, Mohamed M. Hafez, Eman T. Mehanna, Noha M. Mesbah, Dina M. Abo-Elmatty
Naunyn-Schmiedeberg's Archives of Pharmacology.2019; 392(6): 685. CrossRef
Therapeutic experience of saxagliptin as first add-on after metformin in Indian type 2 diabetes patients: A non-interventional, prospective, observational study (ONTARGET-INDIA)
Sanjay Kalra, Sarita Bajaj, AG Unnikrishnan, ManashP Baruah, Rakesh Sahay, V Hardik, Amit Kumar
Indian Journal of Endocrinology and Metabolism.2019; 23(3): 312. CrossRef
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Pablo F. Mora, Eric L. Johnson
Endocrine Practice.2017; 23(1): 89. CrossRef
Treatment of Dyslipidemias to Prevent Cardiovascular Disease in Patients with Type 2 Diabetes
Maryam Khavandi, Francisco Duarte, Henry N. Ginsberg, Gissette Reyes-Soffer
Current Cardiology Reports.2017;[Epub] CrossRef
Sodium butyrate has context-dependent actions on dipeptidyl peptidase-4 and other metabolic parameters
Eun-Sol Lee, Dong-Sung Lee, Prakash Raj Pandeya, Youn-Chul Kim, Dae-Gil Kang, Ho-Sub Lee, Byung-Chul Oh, Dae Ho Lee
The Korean Journal of Physiology & Pharmacology.2017; 21(5): 519. CrossRef
Risk of Myopathy Associated With DPP-4 Inhibitors in Combination With Statins: A Disproportionality Analysis Using Data From the WHO and French Spontaneous Reporting Databases
Vanessa Labat, Mickael Arnaud, Ghada Miremont-Salamé, Francesco Salvo, Bernard Bégaud, Antoine Pariente
Diabetes Care.2017; 40(3): e27. CrossRef
Soluble DPP-4 up-regulates toll-like receptors and augments inflammatory reactions, which are ameliorated by vildagliptin or mannose-6-phosphate
Dong-Sung Lee, Eun-Sol Lee, Md. Morshedul Alam, Jun-Hyeog Jang, Ho-Sub Lee, Hyuncheol Oh, Youn-Chul Kim, Zahid Manzoor, Young-Sang Koh, Dae-Gil Kang, Dae Ho Lee
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Association between DPP4 gene polymorphism and serum lipid levels in Chinese type 2 diabetes individuals
Xiaomin Xing, Yi Han, Xiaojun Zhou, Bo Zhang, Yan Li, Zhongsu Wang, Lin Liao, Lequn Su
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Common medications used by patients with type 2 diabetes mellitus: what are their effects on the lipid profile?
Paul D. Rosenblit
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Maeve Lynch, Tomás B. Ahern, Irene Timoney, Cheryl Sweeney, Genevieve Kelly, Rosalind Hughes, Anne-Marie Tobin, Donal O’Shea, Brian Kirby
Trials.2016;[Epub] CrossRef
Efficacy of different dipeptidyl peptidase-4 (DPP-4) inhibitors on metabolic parameters in patients with type 2 diabetes undergoing dialysis
Se Hee Park, Joo Young Nam, Eugene Han, Yong-ho Lee, Byung-Wan Lee, Beom Seok Kim, Bong-Soo Cha, Chul Sik Kim, Eun Seok Kang
Medicine.2016; 95(32): e4543. CrossRef
Incretin-based therapies for obesity treatment
Aline Haas de Mello, Morgana Prá, Larissa Colonetti Cardoso, Rosiane de Bona Schraiber, Gislaine Tezza Rezin
Metabolism.2015; 64(9): 967. CrossRef
Brain Signaling Systems in the Type 2 Diabetes and Metabolic Syndrome: Promising Target to Treat and Prevent These Diseases
Alexander O Shpakov, Kira V Derkach, Lev M Berstein
Future Science OA.2015;[Epub] CrossRef
Comparative analysis of therapeutic efficiency and costs (experience in Bulgaria) of oral antidiabetic therapies based on glitazones and gliptins
Elena Pavlova Filipova, Katya Hristova Uzunova, Toni Yonkov Vekov
Diabetology & Metabolic Syndrome.2015;[Epub] CrossRef
Antidiabetic Effect of Galantamine: Novel Effect for a Known Centrally Acting Drug
Mennatallah A. Ali, Hanan S. El-Abhar, Maher A. Kamel, Ahmed S. Attia, John Calvert
PLOS ONE.2015; 10(8): e0134648. CrossRef
The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors
Na-Hyung Kim, Taeyang Yu, Dae Ho Lee
BioMed Research International.2014; 2014: 1. CrossRef
A Post Hoc Analysis of HbA1c, Hypoglycemia, and Weight Change Outcomes with Alogliptin vs Glipizide in Older Patients with Type 2 Diabetes
Morgan Bron, Craig Wilson, Penny Fleck
Diabetes Therapy.2014; 5(2): 521. CrossRef
Response: The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes (Diabetes Metab J2014;38:211-9)
EunYeong Choe, Eun Seok Kang
Diabetes & Metabolism Journal.2014; 38(4): 319. CrossRef
Letter: The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes (Diabetes Metab J2014;38:211-9)
Seung-Hwan Lee
Diabetes & Metabolism Journal.2014; 38(4): 317. CrossRef

Glycemic Effectiveness of Metformin-Based Dual-Combination Therapies with Sulphonylurea, Pioglitazone, or DPP4-Inhibitor in Drug-Naïve Korean Type 2 Diabetic Patients: Young Ki Lee, Sun Ok Song, Kwang Joon Kim, Yongin Cho, Younjeong Choi, Yujung Yun, Byung-Wan Lee, Eun-Seok Kang, Bong Soo Cha, Hyun Chul Lee; Diabetes Metab J. 2013;37(6):465-474. Published online December 12, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.6.465

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Abstract PDF PubReader

Background

This study compared the glycemic effectiveness of three metformin-based dual therapies according to baseline hemoglobin A1c (HbA1c) to evaluate the appropriateness of the guideline enforced by the National Health Insurance Corporation of Korea for initial medication of type 2 diabetes (T2D).

Methods

This prospective observational study was conducted across 24 weeks for drug-naïve Korean T2D patients with HbA1c greater than 7.5%. Subjects were first divided into three groups based on the agent combined with metformin (group 1, gliclazide-modified release or glimepiride; group 2, pioglitazone; group 3, sitagliptin). Subjects were also classified into three categories according to baseline HbA1c (category I, 7.5%≤HbA1c<9.0%; category II, 9.0%≤HbA1c<11.0%; category III, 11.0%≤HbA1c).

Results

Among 116 subjects, 99 subjects completed the study, with 88 subjects maintaining the initial medication. While each of the metformin-based dual therapies showed a significant decrease in HbA1c (group 1, 8.9% to 6.4%; group 2, 9.0% to 6.6%; group 3, 9.3% to 6.3%; P<0.001 for each), there was no significant difference in the magnitude of HbA1c change among the groups. While the three HbA1c categories showed significantly different baseline HbA1c levels (8.2% vs. 9.9% vs. 11.9%; P<0.001), endpoint HbA1c was not different (6.4% vs. 6.6% vs. 6.0%; P=0.051).

Conclusion

The three dual therapies using a combination of metformin and either sulfonylurea, pioglitazone, or sitagliptin showed similar glycemic effectiveness among drug-naïve Korean T2D patients. In addition, these regimens were similarly effective across a wide range of baseline HbA1c levels.

Citations

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Initial combination therapy with vildagliptin plus metformin in drug-naïve patients with T2DM: a 24-week real-life study from Asia
Manoj Chawla, Tae Ho Kim, Roberto C. Mirasol, Pathan Faruque, Kathryn Cooke, Peggy Hours-Zesiger, Abhijit Shete
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Sang Soo Kim, In Joo Kim, Kwang Jae Lee, Jeong Hyun Park, Young Il Kim, Young Sil Lee, Sung Chang Chung, Sang Jin Lee
Journal of Diabetes.2017; 9(4): 412. CrossRef
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Jianping Weng
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Gyuri Kim, Sewon Oh, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim, Moon-Kyu Lee
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The Risk of Bladder Cancer in Korean Diabetic Subjects Treated with Pioglitazone: Sun Ok Song, Kwang Joon Kim, Byung-Wan Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee; Diabetes Metab J. 2012;36(5):371-378. Published online October 18, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.5.371

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Background

There is growing concern regarding the increased incidence of bladder cancer in diabetic patients using pioglitazone. This study aimed to investigate the association between bladder cancer and the use of pioglitazone in Korean diabetics.

Methods

This retrospective, matched case-control study included a case group (n=329) of diabetic patients with bladder cancer who presented at the Severance Hospital from November 2005 to June 2011. The control group consisted of patients without bladder cancer (1:2 ratio matching for sex and age, n=658) who were listed on the Severance Hospital diabetes registry.

Results

The percentage of subjects who had ever used pioglitazone was significantly lower in the case group than in the control group (6.4% vs. 15.0%, P<0.001). Multivariate conditional logistic analysis revealed that independent factors affecting bladder cancer were smoking (odds ratio [OR], 11.64; 95% confidence interval [CI], 6.56 to 20.66; P<0.001), coexisting cancer (OR, 6.11; 95% CI, 2.25 to 16.63; P<0.001), and hemoglobin levels (OR, 0.78; 95% CI, 0.69 to 0.88; P<0.001). The OR of the history of pioglitazone use was 2.09 and was not significantly different between the two groups (95% CI, 0.26 to 16.81; P=0.488).

Conclusion

A relationship between pioglitazone use and incidence of bladder cancer was not observed in Korean diabetic patients. This suggests that the risk for bladder cancer in Korean diabetic subjects treated with pioglitazone might be different from that of Caucasian populations. Large-scale, well-designed and multi-center studies are needed to further evaluate this relationship.

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Pioglitazone, Bladder Cancer, and the Presumption of Innocence
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Study design choices for evaluating the comparative safety of diabetes medications: An evaluation of pioglitazone use and risk of bladder cancer in older US adults with type‐2 diabetes
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Pioglitazone use and risk of bladder cancer: a systematic literature review and meta-analysis of observational studies
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Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via Beta Cell ABCA1: Hannah Seok, Ji Young Lee, Eun Mi Park, Se Eun Park, Jae Hyuk Lee, Seungtaek Lim, Byung-Wan Lee, Eun Seok Kang, Hyun Chul Lee, Bong Soo Cha; Diabetes Metab J. 2012;36(4):275-279. Published online August 20, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.4.275

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Background

The aim of this study was to investigate the effects of balsamic vinegar on β-cell dysfunction.

Methods

In this study, 28-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed a normal chow diet or a high-fat diet (HFD) and were provided with tap water or dilute balsamic vinegar for 4 weeks. Oral glucose tolerance tests and histopathological analyses were performed thereafter.

Results

In rats fed both the both chow diet and the HFD, the rats given balsamic vinegar showed increased insulin staining in islets compared with tap water administered rats. Balsamic vinegar administration also increased β-cell ATP-binding cassette transporter subfamily A member 1 (ABCA1) expression in islets and decreased cholesterol levels.

Conclusion

These findings provide the first evidence for an anti-diabetic effect of balsamic vinegar through improvement of β-cell function via increasing β-cell ABCA1 expression.

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Chemical Property and Macrophage Stimulating Activity of Polysaccharides isolated from Brown Rice and Persimmon Vinegars
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Vinegar ingestion at mealtime reduced fasting blood glucose concentrations in healthy adults at risk for type 2 diabetes
Carol S. Johnston, Samantha Quagliano, Serena White
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Glycemic Effects of Once-a-Day Rapid-Acting Insulin Analogue Addition on a Basal Insulin Analogue in Korean Subjects with Poorly Controlled Type 2 Diabetes Mellitus: Eun Yeong Choe, Yong-ho Lee, Byung-Wan Lee, Eun-Seok Kang, Bong Soo Cha, Hyun Chul Lee; Diabetes Metab J. 2012;36(3):230-236. Published online June 14, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.3.230

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Background

The present study investigates the efficacy in glycemic control by adding once-a-day glulisine to glargine as a basal plus regimen and factors influencing glycemic control with the basal plus regimen in Korean subjects with type 2 diabetes.

Methods

In the present retrospective study, subjects previously treated with the basal plus regimens for at least 6 months were reviewed. Changes in glycemic profiles and clinical parameters were evaluated.

Results

A total of 87 subjects were ultimately enrolled in this study. At baseline, mean glycated hemoglobin (A1c) and glycated albumin were 8.5% (8.0% to 9.6%) and 25.2±7.6%, respectively. After treatment with the basal plus regimen, patients had significant reductions of A1c at 6 months (0.8±0.1%, P<0.001) and their postprandial glucose levels were decreased by 48.7±10.3 mg/dL (P<0.001). Multiple logistic regression showed old age (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02 to 1.55), high initial A1c (OR, 22.21; 95% CI, 2.44 to 201.78), and lower amounts of glargine (OR, 0.85; 95% CI, 0.76 to 0.99), and glimepiride (OR, 0.23; 95% CI, 0.06 to 0.93) at baseline were independently associated with good responders whose A1c reduction was more than 0.5%.

Conclusion

The authors suggest a basal plus regimen may be effective in reducing glucose levels of subjects with old age, high initial A1c, and patients on low doses of glimepiride and glargine. Despite the use of high doses of hypoglycemic agents, elderly patients with poorly-controlled diabetes are preferred for early initiation of the basal plus regimen.

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Sulwon Lecture 2011

Post-Renal Transplant Diabetes Mellitus in Korean Subjects: Superimposition of Transplant-Related Immunosuppressant Factors on Genetic and Type 2 Diabetic Risk Factors: Hyun Chul Lee; Diabetes Metab J. 2012;36(3):199-206. Published online June 14, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.3.199

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Postrenal transplantation diabetes mellitus (PTDM), or new-onset diabetes after organ transplantation, is an important chronic transplant-associated complication. Similar to type 2 diabetes, decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind the development of PTDM. However, β-cell dysfunction rather than insulin resistance seems to be a greater contributing factor in the development of PTDM. Increased age, family history of diabetes, ethnicity, genetic variation, obesity, and hepatitis C are partially accountable for an increased underlying risk of PTDM in renal allograft recipients. In addition, the use of and kinds of immunosuppressive agents are key transplant-associated risk factors. Recently, a number of genetic variants or polymorphisms susceptible to immunosuppressants have been reported to be associated with calcineurin inhibition-induced β-cell dysfunction. The identification of high risk factors of PTDM would help prevent PTDM and improve long-term patient outcomes by allowing for personalized immunosuppressant regimens and by managing cardiovascular risk factors.

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Original Articles

Associations between Fatness, Fitness, IGF and IMT among Obese Korean Male Adolescents: Eun Sung Kim, Ji-Hye Park, Mi Kyung Lee, Dong Hoon Lee, Eun Seok Kang, Hyun Chul Lee, Yoonsuk Jekal, Justin Y. Jeon; Diabetes Metab J. 2011;35(6):610-618. Published online December 26, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.6.610

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Background

The purpose of this study was to investigate the association between obesity, fitness levels and cardiovascular (CVD) risk factors, and to identify the correlation between of insulin-like growth factor (IGF)-1, IGF binding protein-3 (IGFBP-3), and carotid intima media thickness (IMT) in Korean adolescents.

Methods

A total of 225 high school males with a mean age of 16.96±0.23 years participated in this study, and their fatness and fitness levels, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, IGF-1, IGFBP-3, and IMT were measured.

Results

The results showed that total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), fasting insulin, HOMA-IR, IGF-1, and IGFBP-3 levels were significantly higher in the most obese group than in the other two groups (tertiles). Muscular and cardiopulmonary fitness were negatively associated with weight, body mass index (BMI), fat mass, body fat, waist circumference (WC), fasting insulin, HOMA-IR, and IMT. IGF-1 and IGFBP-3 levels were correlated with WC, hip circumference (HC), fasting glucose, TG, HDL-C, fasting insulin, and HOMA-IR. IMT levels were significantly associated with weight, BMI, muscle mass, fat mass, percent body fat, WC, HC, systolic blood pressure, diastolic blood pressure and high-sensitivity C-reactive protein.

Conclusion

There was a significant association between increased obesity and decreased fitness and HOMA-IR, IGF, and IMT among adolescents.

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Dietary Oleate Has Beneficial Effects on Every Step of Non-Alcoholic Fatty Liver Disease Progression in a Methionine- and Choline-Deficient Diet-Fed Animal Model: Ji Young Lee, Jae Hoon Moon, Jong Suk Park, Byung-Wan Lee, Eun Seok Kang, Chul Woo Ahn, Hyun Chul Lee, Bong Soo Cha; Diabetes Metab J. 2011;35(5):489-496. Published online October 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.5.489

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Background

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a major cause of liver-related morbidity and mortality. The underlying mechanisms of disease progression remain poorly understood, and primary therapy of NAFLD is not yet established. We investigated the effects of dietary oleate on the development and progression of NAFLD in a methionine- and choline-deficient (MCD) diet-fed animal model.

Methods

A total of 30 C57BL/6J mice were randomly divided into three groups (n=10 in each group) and fed various experimental diets for four weeks: chow, MCD diet, or OMCD (MCD diet with oleate, 0.5 mg/g/day). Liver samples were examined for steatohepatitis and fibrosis parameters and associated genes.

Results

Additional dietary oleate dramatically reduced MCD diet-induced hepatic steatosis. Hepatic carbohydrate responsive element-binding protein was overexpressed in MCD diet-fed mice, and dietary oleate prevented this overexpression (P<0.001). Dietary oleate partially prevented MCD diet-induced serum level increases in aspartate aminotransferase and alanine aminotransferase (P<0.001, respectively). The mRNA expressions of hepatic monocyte chemoattractant protein 1, tumor necrosis factor-α and matrix metalloproteinase-9 were increased in MCD diet-fed mice, and this overexpression of inflammatory molecules was prevented by dietary oleate (P<0.001). Hepatic pericellular fibrosis was observed in MCD diet-fed mice, and dietary oleate prevented this fibrosis. Altogether, dietary oleate prevented MCD diet-induced hepatic steatosis, inflammation and fibrosis.

Conclusion

Dietary oleate has beneficial effects in every step of NAFLD development and progression and could be a nutritional option for NAFLD prevention and treatment.

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Shengying Gu, Shanshan Hu, Shuowen Wang, Chendong Qi, Chenyang Shi, Guorong Fan
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The Effect of Bioactive Aliment Compounds and Micronutrients on Non-Alcoholic Fatty Liver Disease
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Single‐cell transcriptomics stratifies organoid models of metabolic dysfunction‐associated steatotic liver disease
Anja Hess, Stefan D Gentile, Amel Ben Saad, Raza‐Ur Rahman, Tim Habboub, Daniel S Pratt, Alan C Mullen
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Histopathological Examination of the Effects of Tocilizumab and Dexamethasone on the Liver in Rats of Oleic Acid induced Acute Lung Injury
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PPARδ attenuates hepatic steatosis through autophagy-mediated fatty acid oxidation
Lei Tong, Long Wang, Shuangshuang Yao, Lina Jin, Jian Yang, Yifei Zhang, Guang Ning, Zhiguo Zhang
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Butyrate Protects Mice Against Methionine–Choline-Deficient Diet-Induced Non-alcoholic Steatohepatitis by Improving Gut Barrier Function, Attenuating Inflammation and Reducing Endotoxin Levels
Jianzhong Ye, Longxian Lv, Wenrui Wu, Yating Li, Ding Shi, Daiqiong Fang, Feifei Guo, Huiyong Jiang, Ren Yan, Wanchun Ye, Lanjuan Li
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Yun-Yun Chiang, Jane C.-J. Chao
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Dietary oleic acid regulates hepatic lipogenesis through a liver X receptor-dependent signaling
Simon Ducheix, Alexandra Montagner, Arnaud Polizzi, Frédéric Lasserre, Marion Régnier, Alice Marmugi, Fadila Benhamed, Justine Bertrand-Michel, Laila Mselli-Lakhal, Nicolas Loiseau, Pascal G. Martin, Jean-Marc Lobaccaro, Laurent Ferrier, Catherine Postic,
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Postprandial Triglyceride Is Associated with Fasting Triglyceride and HOMA-IR in Korean Subjects with Type 2 Diabetes: Seo Hee Lee, Byung-Wan Lee, Hee Kwan Won, Jae Hoon Moon, Kwang Joon Kim, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee; Diabetes Metab J. 2011;35(4):404-410. Published online August 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.4.404

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Abstract PDF Supplementary Material PubReader

Background

Recent studies indicate postprandial triglyceride (TG) had a better association with cardiovascular events and metabolic syndrome than fasting TG. The authors of the present study investigated the metabolic and clinical relevance of postprandial TG.

Methods

In a cross-sectional retrospective study, the authors of the present study compared fasting and postprandial TG and analyzed the relationship between postprandial TG and various demographic and metabolic parameters in 639 Korean subjects with type 2 diabetes (T2D, group I, n=539) and impaired fasting glucose (IFG, group II, n=100) after ingestion of a standardized liquid meal (total 500 kcal, 17.5 g fat, 68.5 g carbohydrate, and 17.5 g protein).

Results

Fasting and postprandial TG were significantly correlated (r=0.973, r=0.937, P<0.001) in group I and II, respectively. Of the variables, total cholesterol, waist circumference and body mass index were significantly correlated with fasting and postprandial TG in both groups. Only postprandial TG showed a significant correlation with glucose metabolic parameters (e.g., postprandial glucose, homeostatic model assessment of insulin resistance [HOMA-IR], and fasting C-peptide) in subjects with T2D. Multiple regression analysis showed fasting TG and HOMA-IR could be predictable variables for postprandial TG in subjects with T2D.

Conclusion

Postprandial TG was very strongly correlated with fasting TG. The authors of the present study suggest insulin resistance may be more associated with postprandial TG than fasting TG in Korean T2D patients on a low-fat diet.

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Effects of Walking and Physical Activity on Glucose Regulation among Type 2 Diabetics.: Yoonsuk Jekal, Mi Kyung Lee, Eun Sung Kim, Ji Hye Park, Hyun Ji Lee, Seung Jin Han, Eun Seok Kang, Hyun Chul Lee, So Hun Kim, Justin Y Jeon; Korean Diabetes J. 2008;32(1):60-67. Published online February 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.1.60

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Abstract PDF

BACKGROUND
Physical activity, especially walking is strongly recommended to control blood glucose among type 2 diabetic patients. Furthermore, physical activity is one of the most important tools to prevent secondary diabetes complications among type 2 diabetic patients such as retinopathy, nephropathy, neuropathy etc. The purpose of the study was to examine the association between the level of walking and physical activity and glucose control among Korean adults with type 2 diabetes. METHODS: A total of 250 patients with type 2 diabetes (98 males and 152 females) were recruited (mean age = 62.1 +/- 10.2 years) in the current study. The height, weight, waist and hip circumference were measured, and the level of physical activity and total walking hour were measured by physical activity scale for elderly (PASE). High density lipoprotein cholesterol (HDL-C), total cholesterol, triglyceride, fasting glucose and oral glucose tolerance test, creatinine, uric acid, total protein, albumin, hemoglobin A1c were measured. RESULTS: After adjusting for potential covariates such as age, education, occupation income, smoking, and drinking, male patients who spent least time in walking were more likely to have 2 hour serum glucose level in oral glucose tolerance above 200 mg/dL than counterparts who spent most time in walking with age adjusted (Relative Risk (RR) = 11.75, 95% Confidence Interval (CI) = 1.94-71.00). Male patients who were in the least active group were 5.92 time (95% CI = 1.39-25.28) more likely to have 2 hour serum glucose level in oral glucose tolerance over 200 mg/dL than counterparts in the most active group. However, there was no significant finding in females. CONCLUSIONS: The current study showed that physical activity and walking are effective method to maintain glucose tolerance among type 2 diabetic male patients.

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호남권 지역주민의 건강행태와 만성질환 관리현황
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Yujin Lee, Jung-Hyun Kim
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Izadi Morteza, Hosseini Mahboobeh Sadat, Pazham Hossein
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Sang-A Kim, Woong-Sub Park, Su Jeong Yu, Young Ran Chae, Donghee Choi
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Low Levels of Physical Activity Are Associated with Increased Metabolic Syndrome Risk Factors in Korean Adults
Dong Hoon Lee, Yoon Myung Kim, Yoonsuk Jekal, Sukyung Park, Kyong-Chol Kim, Masayo Naruse, Sun Hyun Kim, Sang-Hwan Kim, Ji-Hye Park, Mi Kyung Lee, Sang Hui Chu, Justin Y. Jeon
Diabetes & Metabolism Journal.2013; 37(2): 132. CrossRef
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Yoonsuk Jekal, Mi-Kyung Lee, Sukyung Park, Seung-Hwan Lee, Jun-Young Kim, Jung-Ui Kang, Masayo Naruse, Sang-Hwan Kim, Sun-Hyeon Kim, Sang Hui Chu, Sang-Hoon Suh, Justin Y Jeon
Korean Diabetes Journal.2010; 34(3): 182. CrossRef

Protective Effects of Lithospermic Acid B on Diabetic Nephropathy in OLETF Rats Comparing with Amlodipine and Losartan.: Eun Seok Kang, Beom Seok Kim, Chul Hoon Kim, Gi Ho Seo, Seung Jin Han, Sung Wan Chun, Kyu Yeon Hur, Chul Woo Ahn, Hunjoo Ha, Mankil Jung, Bong Soo Cha, Hyun Chul Lee; Korean Diabetes J. 2008;32(1):10-20. Published online February 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.1.10

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Abstract PDF

BACKGROUND
Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 and type 2 diabetic animal models. We examined the effects of LAB on the prevention of diabetic nephropathy compared with amlodipine, a calcium channel blocker, and losartan, an angiotensin receptor blocker, in Otsuka Long-Evans-Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS: LAB (20 mg/kg), amlodipine (10 mg/kg), or losartan (10 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks. RESULTS: None of LAB, losartan, and amlodipine exhibited effects on blood glucose levels. Treatment with amlodipine or losartan resulted in similar reductions in blood pressure; however, LAB was less effective in lowering blood pressure. Albuminuria was markedly suppressed by losartan and LAB, but not by amlodipine. LAB treatment decreased levels of renal lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta1 (TGF-beta1). CONCLUSION: These results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing oxidative stress and inflammation as potent as losartan.

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

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

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

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

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