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Sang Soo Kim  (Kim SS) 15 Articles
Drug Regimen
Article image
The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study
Jun Sung Moon, Il Rae Park, Sang Soo Kim, Hye Soon Kim, Nam Hoon Kim, Sin Gon Kim, Seung Hyun Ko, Ji Hyun Lee, Inkyu Lee, Bo Kyeong Lee, Kyu Chang Won
Diabetes Metab J. 2023;47(6):818-825.   Published online November 24, 2023
DOI: https://doi.org/10.4093/dmj.2023.0171
  • 4,431 View
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  • 1 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).
Methods
This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.
Results
A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (–63.90±6.89 vs. –55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, –8.47; 95% confidence interval, –16.44 to –0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).
Conclusion
In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Citations

Citations to this article as recorded by  
  • Does Rosuvastatin/Ezetimibe Combination Therapy Offer Potential Benefits for Glucose Metabolism beyond Lipid-Lowering Efficacy in T2DM?
    Il Rae Park, Jun Sung Moon
    Diabetes & Metabolism Journal.2024; 48(3): 387.     CrossRef
Metabolic Risk/Epidemiology
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Current Status of Low-Density Lipoprotein Cholesterol Target Achievement in Patients with Type 2 Diabetes Mellitus in Korea Compared with Recent Guidelines
Soo Jin Yun, In-Kyung Jeong, Jin-Hye Cha, Juneyoung Lee, Ho Chan Cho, Sung Hee Choi, SungWan Chun, Hyun Jeong Jeon, Ho-Cheol Kang, Sang Soo Kim, Seung-Hyun Ko, Gwanpyo Koh, Su Kyoung Kwon, Jae Hyuk Lee, Min Kyong Moon, Junghyun Noh, Cheol-Young Park, Sungrae Kim
Diabetes Metab J. 2022;46(3):464-475.   Published online March 3, 2022
DOI: https://doi.org/10.4093/dmj.2021.0088
  • 8,146 View
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  • 5 Web of Science
  • 8 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We evaluated the achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with type 2 diabetes mellitus (T2DM) according to up-to-date Korean Diabetes Association (KDA), European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS), and American Diabetes Association (ADA) guidelines.
Methods
This retrospective cohort study collected electronic medical record data from patients with T2DM (≥20 years) managed by endocrinologists from 15 hospitals in Korea (January to December 2019). Patients were categorized according to guidelines to assess LDL-C target achievement. KDA (2019): Very High-I (atherosclerotic cardiovascular disease [ASCVD]) <70 mg/dL; Very High-II (target organ damage [TOD], or cardiovascular risk factors [CVRFs]) <70 mg/dL; high (others) <100 mg/dL. ESC/EAS (2019): Very High-I (ASCVD): <55 mg/dL; Very High-II (TOD or ≥3-CVRF) <55 mg/dL; high (diabetes ≥10 years without TOD plus any CVRF) <70 mg/dL; moderate (diabetes <10 years without CVRF) <100 mg/dL. ADA (2019): Very High-I (ASCVD); Very High-II (age ≥40+ TOD, or any CVRF), for high intensity statin or statin combined with ezetimibe.
Results
Among 2,000 T2DM patients (mean age 62.6 years; male 55.9%; mean glycosylated hemoglobin 7.2%) ASCVD prevalence was 24.7%. Of 1,455 (72.8%) patients treated with statins, 73.9% received monotherapy. According to KDA guidelines, LDL-C target achievement rates were 55.2% in Very High-I and 34.9% in Very High-II patients. With ESC/EAS guidelines, target attainment rates were 26.6% in Very High-I, 15.7% in Very High-II, and 25.9% in high risk patients. Based on ADA guidelines, most patients (78.9%) were very-high risk; however, only 15.5% received high-intensity statin or combination therapy.
Conclusion
According to current dyslipidemia management guidelines, LDL-C goal achievement remains suboptimal in Korean patients with T2DM.

Citations

Citations to this article as recorded by  
  • Risk factor control and cardiovascular events in patients with type 2 diabetes mellitus
    Do Kyeong Song, Young Sun Hong, Yeon-Ah Sung, Hyejin Lee, Hidetaka Hamasaki
    PLOS ONE.2024; 19(2): e0299035.     CrossRef
  • Distinct effects of rosuvastatin and rosuvastatin/ezetimibe on senescence markers of CD8+ T cells in patients with type 2 diabetes mellitus: a randomized controlled trial
    Sang-Hyeon Ju, Joung Youl Lim, Minchul Song, Ji Min Kim, Yea Eun Kang, Hyon-Seung Yi, Kyong Hye Joung, Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Monitoring Global Progress in Core Diabetes Control Metrics: Protocol for a Systematic Review of Prevalence (2015–2023)
    John McCaffrey, Samira Barbara Jabakhanji, Roopa Mehta, Steven James, Maisoon Mairghani, Dominika Bhatia, Hazel Ní Chonchubhair, Killian Walsh, Barbara Clyne, Edward W. Gregg
    HRB Open Research.2024; 7: 27.     CrossRef
  • Real-world evidence evaluation of LDL-C in hospitalized patients: a population-based observational study in the timeframe 2021–2022
    Umberto Capece, Chiara Iacomini, Teresa Mezza, Alfredo Cesario, Carlotta Masciocchi, Stefano Patarnello, Andrea Giaccari, Nicoletta Di Giorgi
    Lipids in Health and Disease.2024;[Epub]     CrossRef
  • Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
    Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
    Journal of Lipid and Atherosclerosis.2023; 12(1): 12.     CrossRef
  • Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
    Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
    Diabetes & Metabolism Journal.2023; 47(1): 1.     CrossRef
  • Management of Dyslipidemia in Patients with Diabetes Mellitus
    Kyung Ae Lee
    The Journal of Korean Diabetes.2023; 24(3): 111.     CrossRef
  • Association between carotid atherosclerosis and presence of intracranial atherosclerosis using three-dimensional high-resolution vessel wall magnetic resonance imaging in asymptomatic patients with type 2 diabetes
    Ji Eun Jun, You-Cheol Hwang, Kyu Jeong Ahn, Ho Yeon Chung, Geon-Ho Jahng, Soonchan Park, In-Kyung Jeong, Chang-Woo Ryu
    Diabetes Research and Clinical Practice.2022; 191: 110067.     CrossRef
Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study (Diabetes Metab J 2021;45:675-83)
Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin
Diabetes Metab J. 2022;46(1):162-163.   Published online January 27, 2022
DOI: https://doi.org/10.4093/dmj.2021.0331
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Drug/Regimen
Article image
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 Kim, Hye Soon Kim, Il Seong Nam-Goong, Eun Sook Kim, Jin Ook Chung, Dong-Hyeok Cho, Chang Won Lee, Young Il Kim, Dong Jin Chung, Kyu Chang Won, In Joo Kim, Tae Sun Park, Duk Kyu Kim, Hosang Shon
Diabetes Metab J. 2021;45(5):675-683.   Published online August 12, 2020
DOI: https://doi.org/10.4093/dmj.2020.0107
  • 36,559 View
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  • 10 Web of Science
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Methods

From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.

Results

In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy.

Conclusion

This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Citations

Citations to this article as recorded by  
  • Estimating Type 2 Diabetes Prevalence: A Model of Drug Consumption Data
    Rita Oliveira, Matilde Monteiro-Soares, José Pedro Guerreiro, Rúben Pereira, António Teixeira-Rodrigues
    Pharmacy.2024; 12(1): 18.     CrossRef
  • Disease burden and symptom management in type 2 diabetic patients: A phenomenological study
    Sevgi Demir Çam, Sevda Uzun
    Public Health Nursing.2024;[Epub]     CrossRef
  • Efficacy and safety of enavogliflozin versus dapagliflozin added to metformin plus gemigliptin treatment in patients with type 2 diabetes: A double-blind, randomized, comparator-active study: ENHANCE-D study
    Kyung-Soo Kim, Kyung Ah Han, Tae Nyun Kim, Cheol-Young Park, Jung Hwan Park, Sang Yong Kim, Yong Hyun Kim, Kee Ho Song, Eun Seok Kang, Chul Sik Kim, Gwanpyo Koh, Jun Goo Kang, Mi Kyung Kim, Ji Min Han, Nan Hee Kim, Ji Oh Mok, Jae Hyuk Lee, Soo Lim, Sang S
    Diabetes & Metabolism.2023; 49(4): 101440.     CrossRef
  • Effectiveness and safety of teneligliptin added to patients with type 2 diabetes inadequately controlled by oral triple combination therapy: A multicentre, randomized, double‐blind, and placebo‐controlled study
    Minyoung Lee, Woo‐je Lee, Jae Hyeon Kim, Byung‐Wan Lee
    Diabetes, Obesity and Metabolism.2022; 24(6): 1105.     CrossRef
  • A double‐blind, Randomized controlled trial on glucose‐lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase‐4 inhibitor therapy: REFIND study
    Soree Ryang, Sang Soo Kim, Ji Cheol Bae, Ji Min Han, Su Kyoung Kwon, Young Il Kim, Il Seong Nam‐Goong, Eun Sook Kim, Mi‐kyung Kim, Chang Won Lee, Soyeon Yoo, Gwanpyo Koh, Min Jeong Kwon, Jeong Hyun Park, In Joo Kim
    Diabetes, Obesity and Metabolism.2022; 24(9): 1800.     CrossRef
  • Glycaemic control with add‐on thiazolidinedione or a sodium‐glucose co‐transporter‐2 inhibitor in patients with type 2 diabetes after the failure of an oral triple antidiabetic regimen: A 24‐week, randomized controlled trial
    Jaehyun Bae, Ji Hye Huh, Minyoung Lee, Yong‐Ho Lee, Byung‐Wan Lee
    Diabetes, Obesity and Metabolism.2021; 23(2): 609.     CrossRef
Lifesytle
Combined Aerobic and Resistance Exercise Training Reduces Circulating Apolipoprotein J Levels and Improves Insulin Resistance in Postmenopausal Diabetic Women
Yun Kyung Jeon, Sang Soo Kim, Jong Ho Kim, Hyun Jeong Kim, Hyun Jun Kim, Jang Jun Park, Yuen Suk Cho, So Hee Joung, Ji Ryang Kim, Bo Hyun Kim, Sang Heon Song, In Joo Kim, Yong Ki Kim, Young-Bum Kim
Diabetes Metab J. 2020;44(1):103-112.   Published online February 21, 2020
DOI: https://doi.org/10.4093/dmj.2018.0160
  • 9,652 View
  • 169 Download
  • 13 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus.

Methods

Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed.

Results

In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt.

Conclusion

Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.

Citations

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  • The function of previously unappreciated exerkines secreted by muscle in regulation of neurodegenerative diseases
    Xuepeng Bian, Qian Wang, Yibing Wang, Shujie Lou
    Frontiers in Molecular Neuroscience.2024;[Epub]     CrossRef
  • A randomized controlled trial of an app-based intervention on physical activity and glycemic control in people with type 2 diabetes
    Gyuri Kim, Seohyun Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim
    BMC Medicine.2024;[Epub]     CrossRef
  • Exercise modalities for type 2 diabetes: A systematic review and network meta‐analysis of randomized trials
    Liangying Hou, Qi Wang, Bei Pan, Rui Li, Yanfei Li, Juanjuan He, Tianzhu Qin, Liujiao Cao, Na Zhang, Changhao Cao, Long Ge, Kehu Yang
    Diabetes/Metabolism Research and Reviews.2023;[Epub]     CrossRef
  • Estimating the Effect of Aerobic Exercise Training on Novel Lipid Biomarkers: A Systematic Review and Multivariate Meta-Analysis of Randomized Controlled Trials
    Gina Wood, Emily Taylor, Vanessa Ng, Anna Murrell, Aditya Patil, Tom van der Touw, Mitch Wolden, Nick Andronicos, Neil A. Smart
    Sports Medicine.2023; 53(4): 871.     CrossRef
  • 2023 update on Italian guidelines for the treatment of type 2 diabetes
    Edoardo Mannucci, Riccardo Candido, Lina delle Monache, Marco Gallo, Andrea Giaccari, Maria Luisa Masini, Angela Mazzone, Gerardo Medea, Basilio Pintaudi, Giovanni Targher, Marina Trento, Giuseppe Turchetti, Valentina Lorenzoni, Matteo Monami
    Acta Diabetologica.2023; 60(8): 1119.     CrossRef
  • The Effect of Eight Weeks of Concurrent Training on Serum Levels of Paraxonase-1, Irisin, Lipid Profile, and Insulin Resistance in Men With Metabolic Syndrome
    Seyed Amir Hosain Diba Hosaini, Morvarid Vafaee, Bahram Abedi
    Hormozgan Medical Journal.2023; 27(1): 43.     CrossRef
  • An Overview of the TRP-Oxidative Stress Axis in Metabolic Syndrome: Insights for Novel Therapeutic Approaches
    Mizael C. Araújo, Suzany H. S. Soczek, Jaqueline P. Pontes, Leonardo A. C. Marques, Gabriela S. Santos, Gisele Simão, Laryssa R. Bueno, Daniele Maria-Ferreira, Marcelo N. Muscará, Elizabeth S. Fernandes
    Cells.2022; 11(8): 1292.     CrossRef
  • Effect of Yijinjing combined with elastic band exercise on muscle mass and function in middle-aged and elderly patients with prediabetes: A randomized controlled trial
    Yunda Huang, Junhua Han, Qing Gu, Yanwei Cai, Jingyuan Li, Shasha Wang, Suijun Wang, Ru Wang, Xiangyun Liu
    Frontiers in Medicine.2022;[Epub]     CrossRef
  • Effect of combined aerobic and resistance exercise on blood pressure in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials
    Huihui Xi, Yayu He, Yirou Niu, Xin Sui, Jun Zhang, Ruiting Zhu, Haiyan Xu, Shuang Zhang, Yang Li, Yuan Yuan, Lirong Guo
    Experimental Gerontology.2021; 155: 111560.     CrossRef
  • Effects of Augmented-Reality-Based Exercise on Muscle Parameters, Physical Performance, and Exercise Self-Efficacy for Older Adults
    Sangwan Jeon, Jiyoun Kim
    International Journal of Environmental Research and Public Health.2020; 17(9): 3260.     CrossRef
  • Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity
    Ji A Seo, Min-Cheol Kang, Won-Mo Yang, Won Min Hwang, Sang Soo Kim, Soo Hyun Hong, Jee-In Heo, Achana Vijyakumar, Leandro Pereira de Moura, Aykut Uner, Hu Huang, Seung Hwan Lee, Inês S. Lima, Kyong Soo Park, Min Seon Kim, Yossi Dagon, Thomas E. Willnow, V
    Nature Communications.2020;[Epub]     CrossRef
  • Impact of Skeletal Muscle Mass on Metabolic Health
    Gyuri Kim, Jae Hyeon Kim
    Endocrinology and Metabolism.2020; 35(1): 1.     CrossRef
  • Habitual Combined Exercise Protects against Age-Associated Decline in Vascular Function and Lipid Profiles in Elderly Postmenopausal Women
    Elizabeth J. Pekas, John Shin, Won-Mok Son, Ronald J. Headid, Song-Young Park
    International Journal of Environmental Research and Public Health.2020; 17(11): 3893.     CrossRef
Drug/Regimen
Efficacy and Safety of Pioglitazone versus Glimepiride after Metformin and Alogliptin Combination Therapy: A Randomized, Open-Label, Multicenter, Parallel-Controlled Study
Jeong Mi Kim, Sang Soo Kim, Jong Ho Kim, Mi Kyung Kim, Tae Nyun Kim, Soon Hee Lee, Chang Won Lee, Ja Young Park, Eun Sook Kim, Kwang Jae Lee, Young Sik Choi, Duk Kyu Kim, In Joo Kim
Diabetes Metab J. 2020;44(1):67-77.   Published online July 11, 2019
DOI: https://doi.org/10.4093/dmj.2018.0274
  • 8,497 View
  • 176 Download
  • 8 Web of Science
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AbstractAbstract PDFPubReader   
Background

There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM.

Methods

This multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investigator's judgement.

Results

Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: −0.81%, P<0.001; glimepiride: −1.05%, P<0.001). However, the pioglitazone-treated group exhibited significantly higher high density lipoprotein cholesterol levels (P<0.001) and significantly lower homeostatic model assessment of insulin resistance values (P<0.001). Relative to pioglitazone, adding glimepiride to metformin plus alogliptin markedly increased the risk of hypoglycemia (pioglitazone: 1/69 cases [1.45%], glimepiride: 14/66 cases [21.21%]; P<0.001).

Conclusion

Among patients with T2DM inadequately controlled using metformin plus alogliptin, the addition of pioglitazone provided comparable glycemic control and various benefits (improvements in lipid profiles, insulin resistance, and hypoglycemia risk) relative to the addition of glimepiride.

Citations

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  • Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial
    Ji-Yeon Park, Joonyub Lee, Yoon-Hee Choi, Kyung Wan Min, Kyung Ah Han, Kyu Jeung Ahn, Soo Lim, Young-Hyun Kim, Chul Woo Ahn, Kyung Mook Choi, Kun-Ho Yoon
    Diabetes & Metabolism Journal.2024; 48(5): 915.     CrossRef
  • Efficacy and Safety of Pioglitazone Add-on in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin and Dapagliflozin: A Multicenter, Randomized, Double-blind, and Placebo-controlled Study
    Yun Kyung Cho, Kyung-Soo Kim, Byung-Wan Lee, Jun Hwa Hong, Jae Myung Yu, Soo Lim, Ye An Kim, Chang Beom Lee, Sang Soo Kim, Soo Heon Kwak, Woo Je Lee
    Clinical Therapeutics.2024; 46(9): 662.     CrossRef
  • Pioglitazone as Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Dapagliflozin and Metformin: Double-Blind, Randomized, Placebo-Controlled Trial
    Ji Hye Heo, Kyung Ah Han, Jun Hwa Hong, Hyun-Ae Seo, Eun-Gyoung Hong, Jae Myung Yu, Hye Seung Jung, Bong-Soo Cha
    Diabetes & Metabolism Journal.2024; 48(5): 937.     CrossRef
  • Cost-effectiveness and budget impact analysis of fixed combination of alogliptin and pioglitazone in the treatment of type 2 diabetes mellitus
    Yu.V. Strunina, N.A. Petunina
    Medical Technologies. Assessment and Choice.2023; (3): 70.     CrossRef
  • Pioglitazone-Enhanced Brown Fat Whitening Contributes to Weight Gain in Diet-Induced Obese Mice
    Piaojian Yu, Wei Wang, Wanrong Guo, Lidan Cheng, Zhiping Wan, Yanglei Cheng, Yunfeng Shen, Fen Xu
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  • Compliance with Cardiovascular Prevention Guidelines in Type 2 Diabetes Individuals in a Middle-Income Region: A Cross-Sectional Analysis
    Joaquim Barreto, Beatriz Luchiari, Vaneza L. W. Wolf, Isabella Bonilha, Ticiane G. Bovi, Barbara S. Assato, Ikaro Breder, Sheila T. Kimura-Medorima, Daniel B. Munhoz, Thiago Quinaglia, Otavio R. Coelho-Filho, Luiz Sergio F. Carvalho, Wilson Nadruz, Andrei
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  • Effects of Glimepiride Combined with Recombinant Human Insulin Injection on Serum IGF-1, VEGF and TRACP-5b Oxidative Stress Levels in Patients with Type 2 Diabetes Mellitus
    Xue Chen, Sheng Kang, Zeqing Bao, Ciara Hughes
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    Diabetes, Obesity and Metabolism.2021; 23(2): 609.     CrossRef
  • Development and validation of a sensitive LC-MS/MS method for pioglitazone: application towards pharmacokinetic and tissue distribution study in rats
    Kusuma Kumari G., Praveen Thaggikuppe Krishnamurthy, Ravi Kiran Ammu V. V. V., Kurawattimath Vishwanath, S. T. Narenderan, B. Babu, Nagappan Krishnaveni
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  • Compliance with Cardiovascular Prevention Guidelines in Individuals with Type 2 Diabetes in a Middle-Income Region: Cross-Sectional Analysis
    Joaquim Barreto, Beatriz Luchiari, Vaneza Lira W. Wolf, Isabella Bonilha, Ticiane G. Bovi, Barbara S. Assato, Ikaro Breder, Sheila T. Kimura-Medorima, Daniel B. Munhoz, Thiago Quinaglia, Otavio R. Coelho-Filho, Luiz Sérgio Fernandes de Carvalho, Wilson Na
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Obesity and Metabolic Syndrome
The Relationship between Thyroid Function and Different Obesity Phenotypes in Korean Euthyroid Adults
Jeong Mi Kim, Bo Hyun Kim, Hyungi Lee, Eun Heui Kim, Mijin Kim, Jong Ho Kim, Yun Kyung Jeon, Sang Soo Kim, In Joo Kim, Yong Ki Kim
Diabetes Metab J. 2019;43(6):867-878.   Published online April 3, 2019
DOI: https://doi.org/10.4093/dmj.2018.0130
  • 6,683 View
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  • 19 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Thyroid disease and metabolic syndrome are both associated with cardiovascular disease. The aim of this study was to investigate the correlation between thyroid hormones and obesity sub-phenotypes using nationwide data from Korea, a country known to be iodine replete.

Methods

This study was based on data obtained from the sixth Korea National Health and Nutrition Examination Survey, administered from 2013 to 2015. A total of 13,873 participants aged ≥19 years were included, and classified into four groups: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO) by body fat on the basis of body mass index and metabolic health.

Results

At baseline, serum free thyroxine (fT4) values were significantly higher in the MHNO phenotype (MHNO, 1.27±0.01 ng/dL; MHO, 1.25±0.01 ng/dL; MUNO, 1.24±0.01 ng/dL; MUO, 1.24±0.01 ng/dL, P<0.001) in total study population. However, this significant association no longer remained after adjustment for age, urine iodine concentration, and smoking (P=0.085). After adjustment for confounders, statistically significant association was observed between lower thyroid stimulating hormone (TSH) and MHNO phenotype (P=0.044). In men participants (not women), higher fT4 values were significantly associated with MHNO phenotype (P<0.001). However, no significant association was observed between thyroid function (TSH or fT4) and obesity phenotypes in groups classified by age (cutoff age of 55 years).

Conclusion

Although there was a difference by age and sex, we found that the decrease of TSH and the increase of fT4 values were associated with MHNO.

Citations

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Clinical Care/Education
Glycemic Effects of Rebaudioside A and Erythritol in People with Glucose Intolerance
Dong Hee Shin, Ji Hye Lee, Myung Shin Kang, Tae Hoon Kim, Su Jin Jeong, Chong Hwa Kim, Sang Soo Kim, In Joo Kim
Diabetes Metab J. 2016;40(4):283-289.   Published online June 15, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.4.283
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AbstractAbstract PDFPubReader   
Background

Rebaudioside A and erythritol are nonnutritive sweeteners. There have been several studies of their glycemic effects, but the outcomes remain controversial. The purpose of this study was to evaluate the glycemic effects of rebaudioside A and erythritol as a sweetener in people with glucose intolerance.

Methods

This trial evaluated the glycemic effect after 2 weeks of consumption of rebaudioside A and erythritol as sweeteners in a pre-diabetic population. The patients were evaluated for fructosamine, fasting plasma glucose, C-peptide, insulin, and 2-hour plasma glucose before and after consumption of sweetener. The primary outcome was a change in fructosamine levels from the baseline to the end of treatment. Secondary outcomes were the changes in levels of fasting plasma glucose and 2-hour plasma glucose.

Results

From the baseline to the end of experiment, the changes in fructosamine levels after consumption of rebaudioside A and erythritol, did not differ significantly (244.00±19.57 vs. 241.68±23.39 µmol/L, P=0.366). The change in levels from the baseline to end of the study for rebaudioside A and erythritol were fasting plasma glucose (102.56±10.72 vs. 101.32±9.20 mg/dL), 2-hour plasma glucose (154.92±54.53 vs. 141.92±42.22 mg/dL), insulin (7.56±4.29 vs. 7.20±5.12 IU/mL), and C-peptide (2.92±1.61 vs. 2.73±1.31 ng/mL), respectively, and also did not differ significantly (P>0.05 for all).

Conclusion

Our study suggests that consumption of rebaudioside A and erythritol does not alter the glucose homeostasis in people with glucose intolerance.

Citations

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Others
Comparison of Vildagliptin and Pioglitazone in Korean Patients with Type 2 Diabetes Inadequately Controlled with Metformin
Jong Ho Kim, Sang Soo Kim, Hong Sun Baek, In Kyu Lee, Dong Jin Chung, Ho Sang Sohn, Hak Yeon Bae, Mi Kyung Kim, Jeong Hyun Park, Young Sik Choi, Young Il Kim, Jong Ryeal Hahm, Chang Won Lee, Sung Rae Jo, Mi Kyung Park, Kwang Jae Lee, In Joo Kim
Diabetes Metab J. 2016;40(3):230-239.   Published online April 5, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.3.230
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We compared the efficacies of vildagliptin (50 mg twice daily) relative to pioglitazone (15 mg once daily) as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c) levels in Korean patients with type 2 diabetes.

Methods

The present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin.

Results

The mean changes in HbA1c levels from baseline were –0.94% in the vildagliptin group and –0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG) levels were –60.2 mg/dL in the vildagliptin group and –38.2 mg/dL in the pioglitazone group and these values significantly differed (P=0.040). There were significant decreases in the levels of total, low density lipoprotein, high density lipoprotein (HDL), and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group. The mean change in body weight was –0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group, which were also significantly different (P=0.002).

Conclusion

As an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.

Citations

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    Swetha R. Reghunath, Muhammed Rashid, Viji Pulikkel Chandran, Girish Thunga, K.N. Shivashankar, Leelavathi D. Acharya
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Clinical Care/Education
Insulin Initiation in Insulin-Naïve Korean Type 2 Diabetic Patients Inadequately Controlled on Oral Antidiabetic Drugs in Real-World Practice: The Modality of Insulin Treatment Evaluation Study
Sang Soo Kim, In Joo Kim, Yong Ki Kim, Kun Ho Yoon, Ho Young Son, Sung Woo Park, Yeon Ah Sung, Hong Sun Baek
Diabetes Metab J. 2015;39(6):481-488.   Published online November 25, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.481
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AbstractAbstract PDFPubReader   
Background

The Modality of Insulin Treatment Evaluation (MOTIV) study was performed to provide real-world data concerning insulin initiation in Korean type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with oral hypoglycemic agents (OHAs).

Methods

This multicenter, non-interventional, prospective, observational study enrolled T2DM patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0%) who had been on OHAs for ≥3 months and were already decided to introduce basal insulin by their physician prior to the start of the study. All treatment decisions were at the physician's discretion to reflect real-world practice.

Results

A total of 9,196 patients were enrolled, and 8,636 patients were included in the analysis (mean duration of diabetes, 8.9 years; mean HbA1c, 9.2%). Basal insulin plus one OHA was the most frequently (51.0%) used regimen. After 6 months of basal insulin treatment, HbA1c decreased to 7.4% and 44.5% of patients reached HbA1c <7%. Body weight increased from 65.2 kg to 65.5 kg, which was not significant. Meanwhile, there was significant increase in the mean daily insulin dose from 16.9 IU at baseline to 24.5 IU at month 6 (P<0.001). Overall, 17.6% of patients experienced at least one hypoglycemic event.

Conclusion

In a real-world setting, the initiation of basal insulin is an effective and well-tolerated treatment option in Korean patients with T2DM who are failing to meet targets with OHA therapy.

Citations

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    Eun-Gyoung Hong, Kyung-Wan Min, Jung Soo Lim, Kyu-Jeung Ahn, Chul Woo Ahn, Jae-Myung Yu, Hye Soon Kim, Hyun Jin Kim, Won Kim, Dong Han Kim, Hak Chul Jang
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Clinical Characteristics of Diabetic Patients Transferred to Korean Referral Hospitals
Min Young Oh, Sang Soo Kim, In Joo Kim, In Kyu Lee, Hong Sun Baek, Hyoung Woo Lee, Min Young Chung
Diabetes Metab J. 2014;38(5):388-394.   Published online October 17, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.5.388
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AbstractAbstract PDFPubReader   
Background

We evaluated the disease profile and clinical management, including the status of both glycemic control and complications, in patients with diabetes who were transferred to referral hospitals in Korea.

Methods

Patients referred to 20 referral hospitals in Gyeongsangnam/Gyeongsangbuk-do and Jeollanam/Jeollabuk-do with at least a 1-year history of diabetes between January and June 2011 were retrospectively reviewed using medical records, laboratory tests, and questionnaires.

Results

A total of 654 patients were enrolled in the study. In total, 437 patients (67%) were transferred from clinics and 197 (30%) patients were transferred from hospitals. A total of 279 patients (43%) visited higher medical institutions without a written medical request. The main reason for the referral was glycemic control in 433 patients (66%). Seventy-three patients (11%) had received more than one session of diabetic education. Only 177 patients (27%) had been routinely self-monitoring blood glucose, and 146 patients (22%) were monitoring hemoglobin A1c. In addition, proper evaluations for diabetic complications were performed for 74 patients (11%). The most common complication was neuropathy (32%) followed by nephropathy (31%). In total, 538 patients (82%) had been taking oral hypoglycemic agents. A relatively large number of patients (44%) had been taking antihypertensive medications.

Conclusion

We investigated the clinical characteristics of diabetic patients and identified specific problems in diabetic management prior to the transfer. We also found several problems in the medical system, which were divided into three medical institutions having different roles in Korea. Our findings suggested that the relationships among medical institutions have to be improved, particularly for diabetes.

Citations

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    PLOS ONE.2024; 19(2): e0287496.     CrossRef
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    Youqian Zhang, Entong Ren, Chunlong Zhang, Yang Wang, Xiaohe Chen, Lin Li
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    Soree Ryang, Sang Soo Kim, Ji Cheol Bae, Ji Min Han, Su Kyoung Kwon, Young Il Kim, Il Seong Nam‐Goong, Eun Sook Kim, Mi‐kyung Kim, Chang Won Lee, Soyeon Yoo, Gwanpyo Koh, Min Jeong Kwon, Jeong Hyun Park, In Joo Kim
    Diabetes, Obesity and Metabolism.2022; 24(9): 1800.     CrossRef
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Current Status of Prescription in Type 2 Diabetic Patients from General Hospitals in Busan
Ji Hye Suk, Chang Won Lee, Sung Pyo Son, Min Cheol Kim, Jun Hyeob Ahn, Kwang Jae Lee, Ja Young Park, Sun Hye Shin, Min Jeong Kwon, Sang Soo Kim, Bo Hyun Kim, Soon Hee Lee, Jeong Hyun Park, In Joo Kim
Diabetes Metab J. 2014;38(3):230-239.   Published online June 17, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.3.230
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AbstractAbstract PDFPubReader   
Background

Data regarding the prescription status of individuals with diabetes are limited. This study was an analysis of participants from the relationship between cardiovascular disease and brachial-ankle pulse wave velocity in patients with type 2 diabetes (REBOUND) Study, which was a prospective multicenter cohort study recruited from eight general hospitals in Busan, Korea. We performed this study to investigate the current status of prescription in Korean type 2 diabetic patients.

Methods

Type 2 diabetic patients aged 30 years or more were recruited and data were collected for demographics, medical history, medications, blood pressure, and laboratory tests.

Results

Three thousands and fifty-eight type 2 diabetic patients were recruited. Mean age, duration of diabetes, and HbA1c were 59 years, 7.6 years, and 7.2%, respectively. Prevalence of hypertension was 66%. Overall, 7.3% of patients were treated with diet and exercise only, 68.2% with oral hypoglycemic agents (OHAs) only, 5.3% with insulin only, and 19.2% with both insulin and OHA. The percentage of patients using antihypertensive, antidyslipidemic, antiplatelet agents was similar as about 60%. The prevalence of statins and aspirin users was 52% and 32%, respectively.

Conclusion

In our study, two thirds of type 2 diabetic patients were treated with OHA only, and one fifth with insulin plus OHA, and 5% with insulin only. More than half of the patients were using each of antihypertensive, antidyslipidemic, or antiplatelet agents. About a half of the patients were treated with statins and one third were treated with aspirin.

Citations

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  • A double‐blind, Randomized controlled trial on glucose‐lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase‐4 inhibitor therapy: REFIND study
    Soree Ryang, Sang Soo Kim, Ji Cheol Bae, Ji Min Han, Su Kyoung Kwon, Young Il Kim, Il Seong Nam‐Goong, Eun Sook Kim, Mi‐kyung Kim, Chang Won Lee, Soyeon Yoo, Gwanpyo Koh, Min Jeong Kwon, Jeong Hyun Park, In Joo Kim
    Diabetes, Obesity and Metabolism.2022; 24(9): 1800.     CrossRef
  • Arterial stiffness is an independent predictor for risk of mortality in patients with type 2 diabetes mellitus: the REBOUND study
    Jeong Mi Kim, Sang Soo Kim, In Joo Kim, Jong Ho Kim, Bo Hyun Kim, Mi Kyung Kim, Soon Hee Lee, Chang Won Lee, Min Chul Kim, Jun Hyeob Ahn, Jinmi Kim
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    Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
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    Yeoree Yang, Jeong-Ah Shin, Hae Kyung Yang, Seung-Hwan Lee, Seung-Hyun Ko, Yu-Bae Ahn, Kun-Ho Yoon, Jae-Hyoung Cho
    Diabetes & Metabolism Journal.2016; 40(6): 454.     CrossRef
  • Comparison of Vildagliptin and Pioglitazone in Korean Patients with Type 2 Diabetes Inadequately Controlled with Metformin
    Jong Ho Kim, Sang Soo Kim, Hong Sun Baek, In Kyu Lee, Dong Jin Chung, Ho Sang Sohn, Hak Yeon Bae, Mi Kyung Kim, Jeong Hyun Park, Young Sik Choi, Young Il Kim, Jong Ryeal Hahm, Chang Won Lee, Sung Rae Jo, Mi Kyung Park, Kwang Jae Lee, In Joo Kim
    Diabetes & Metabolism Journal.2016; 40(3): 230.     CrossRef
Current Status of Diabetic Peripheral Neuropathy in Korea: Report of a Hospital-Based Study of Type 2 Diabetic Patients in Korea by the Diabetic Neuropathy Study Group of the Korean Diabetes Association
Jong Chul Won, Sang Soo Kim, Kyung Soo Ko, Bong-Yun Cha
Diabetes Metab J. 2014;38(1):25-31.   Published online February 19, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.1.25
  • 4,347 View
  • 56 Download
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AbstractAbstract PDFPubReader   

Diabetic peripheral neuropathy (DPN) is the most common complication associated with diabetes. DPN can present as a loss of sensation, may lead to neuropathic ulcers, and is a leading cause of amputation. Reported estimates of the prevalence of DPN vary due to differences in study populations and diagnostic criteria. Furthermore, the epidemiology and clinical characteristics of DPN in Korean patients with type 2 diabetes mellitus (T2DM) are not as well understood as those of other complications of diabetes such as retinal and renal disease. Recently, the Diabetic Neuropathy Study Group of the Korean Diabetes Association (KDA) conducted a study investigating the impact of DPN on disease burden and quality of life in patients with T2DM and has published some data that are representative of the nation. This review investigated the prevalence and associated clinical implications of DPN in Korean patients with diabetes based on the KDA study.

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Relationships between Brachial-Ankle Pulse Wave Velocity and Peripheral Neuropathy in Type 2 Diabetes
Byung Kil Ha, Bong Gun Kim, Dong Hyun Kim, Soon Il Lee, Soon Myung Jung, Ja Young Park, Chang Won Lee, Sang Soo Kim, Bo Hyun Kim, In Ju Kim
Diabetes Metab J. 2012;36(6):443-451.   Published online December 12, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.6.443
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AbstractAbstract PDFPubReader   
Background

Brachial-ankle pulse wave velocity (baPWV) is known to be a good surrogate marker of clinical atherosclerosis. Atherosclerosis is a major predictor for developing neuropathy. The goal of this study was to determine the relationship between baPWV and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes.

Methods

A retrospective cross-sectional study was conducted involving 692 patients with type 2 diabetes. The correlation between increased baPWV and DPN, neurological symptoms, and neurological assessment was analyzed. DPN was examined using the total symptom score (TSS), ankle reflexes, the vibration test, and the 10-g monofilament test. DPN was defined as TSS ≥2 and an abnormal neurological assessment. Data were expressed as means±standard deviation for normally distributed data and as median (interquartile range) for non-normally distributed data. Independent t-tests or chi-square tests were used to make comparisons between groups, and a multiple logistic regression test was used to evaluate independent predictors of DPN. The Mantel-Haenszel chi-square test was used to adjust for age.

Results

Patients with DPN had higher baPWV and systolic blood pressure, and were more likely to be older and female, when compared to the control group. According to univariate analysis of risk factors for DPN, the odds ratio of the baPWV ≥1,600 cm/sec was 1.611 (95% confidence interval [CI], 1.072 to 2.422; P=0.021) and the odds ratio in female was 1.816 (95% CI, 1.195 to 2.760; P=0.005).

Conclusion

Increased baPWV was significantly correlated with peripheral neuropathy in patients with type 2 diabetes.

Citations

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Fracture Incidence and Risk of Osteoporosis in Female Type 2 Diabetic Patients in Korea
Jong Kwan Jung, Hyo Jeong Kim, Hong Kyu Lee, Sang Soo Kim, Chan Soo Shin, Jin Taek Kim
Diabetes Metab J. 2012;36(2):144-150.   Published online April 17, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.2.144
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AbstractAbstract PDFPubReader   
Background

There are no published data regarding fracture risk in type 2 diabetic patients in Korea. In this study, we compared the fracture incidence and risk of osteoporosis of type 2 diabetic female patients with those in a non-diabetic hypertensive cohort.

Methods

The incidence of fracture in a type 2 diabetic cohort was compared with that in a non-diabetic hypertensive cohort over the course of 7 years. Female type 2 diabetic and non-diabetic hypertensive patients who visited Eulji General Hospital outpatient clinic from January 2004 to April 2004 were assigned to the diabetic cohort and the non-diabetic hypertensive cohort, respectively. Surveys on fracture event, use of anti-osteoporosis medications, and bone mineral density were performed.

Results

The number of fractures was 88 in the female diabetic cohort (n=1,268, 60.6±11.5 years) and 57 in the female non-diabetic hypertensive cohort (n=1,014, 61.4±11.7 years). The RR in the diabetic cohort was 1.38 (P=0.064; 95% confidence interval [CI], 0.98 to 1.94) when adjusted for age. Diabetic patients with microvascular complications (61.0%) showed a higher RR of 1.81 (P=0.014; 95% CI, 1.13 to 2.92) compared with those without these complications. The prevalence of osteoporosis was comparable between the groups, while use of anti-osteoporosis medication was more common in the diabetic cohort (12.8%) than in the hypertensive cohort (4.5%) (P<0.001).

Conclusion

In our study, a higher fracture risk was observed in female type 2 diabetics with microvascular complications. Special concern for this risk group is warranted.

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