Diabetes & Metabolism Journal

Original Article

Drug Regimen
Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension: Jun Sung Moon, Il Rae Park, Hae Jin Kim, Choon Hee Chung, Kyu Chang Won, Kyung Ah Han, Cheol-Young Park, Jong Chul Won, Dong Jun Kim, Gwan Pyo Koh, Eun Sook Kim, Jae Myung Yu, Eun-Gyoung Hong, Chang Beom Lee, Kun-Ho Yoon; Diabetes Metab J. 2023;47(6):808-817. Published online September 26, 2023; DOI: https://doi.org/10.4093/dmj.2022.0387

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Background
This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination.
Methods
In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998).
Results
Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group.
Conclusion
Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Citations

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Efficacy and safety of dapagliflozin add‐on to evogliptin plus metformin therapy in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled study
In‐Kyung Jeong, Kyung Mook Choi, Kyung Ah Han, Kyoung‐Ah Kim, In Joo Kim, Seung Jin Han, Won Young Lee, Soon Jib Yoo
Diabetes, Obesity and Metabolism.2024;[Epub] CrossRef

Response

Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015) (Diabetes Metab J 2021;45:115-9): Seong-Su Moon, Chong Hwa Kim, Seon Mee Kang, Eun Sook Kim, Tae Jung Oh, Jae-Seung Yun, Ho Chan Cho, Dae Jung Kim, Tae Sun Park; Diabetes Metab J. 2021;45(3):459-460. Published online May 25, 2021; DOI: https://doi.org/10.4093/dmj.2021.0084

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Comorbidity Patterns and Management in Inpatients with Endocrine Diseases by Age Groups in South Korea: Nationwide Data
Sung-Soo Kim, Hun-Sung Kim
Journal of Personalized Medicine.2023; 14(1): 42. CrossRef

Brief Report

Complications
Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015): Seong-Su Moon, Chong Hwa Kim, Seon Mee Kang, Eun Sook Kim, Tae Jung Oh, Jae-Seung Yun, Ho Chan Cho, Dae Jung Kim, Tae Sun Park; Diabetes Metab J. 2021;45(1):115-119. Published online December 18, 2020; DOI: https://doi.org/10.4093/dmj.2020.0120

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This report presents the status of diabetic neuropathy (DN) in Korea as determined using a National Health Insurance ServiceNational Sample Cohort (NHIS-NSC). Annual prevalences of DN were estimated by age and gender using descriptive statistics. Pharmacological treatments for DN were also analyzed. The annual prevalence of DN increased from 24.9% in 2006 to 26.6% in 2007, and thereafter, gradually subsided to 20.8% in 2015. In most cases, pharmacological treatments involved a single drug, which accounted for 91.6% of total prescriptions in 2015. The most commonly used drugs (in decreasing order) were thioctic acid, an anti-convulsive agent, or a tricyclic antidepressant. In conclusion, the prevalence of DN decreased over the 10-year study period. Thioctic acid monotherapy was usually prescribed for DN. To reduce the socio-economic burden of DN, more attention should be paid to the diagnosis of this condition and to the appropriate management of patients.

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Emily X. Zhang, Cyrus Yazdi, Rahib K. Islam, Ahmed I. Anwar, Alana Alvares-Amado, Horace Townsend, Kaitlyn E. Allen, Elena Plakotaris, Jon D. Hirsch, Ross G. Rieger, Varsha Allampalli, Jamal Hasoon, Kazi N. Islam, Sahar Shekoohi, Alan D. Kaye, Christopher
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Hyunji Koo, Seung Hun You, Sewon Park, Kyeong Hye Jeong, Nakyung Jeon, Sun-Young Jung
European Journal of Clinical Pharmacology.2023; 79(1): 159. CrossRef
How does diabetic peripheral neuropathy impact patients' burden of illness and the economy? A retrospective study in Beijing, China
Qi Pan, Sijia Fei, Lina Zhang, Huan Chen, Jingyi Luo, Weihao Wang, Fei Xiao, Lixin Guo
Frontiers in Public Health.2023;[Epub] CrossRef
Chronic disease management program applied to type 2 diabetes patients and prevention of diabetic complications: a retrospective cohort study using nationwide data
Min Kyung Hyun, Jang Won Lee, Seung-Hyun Ko
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Pharmacological and Nonpharmacological Treatments for Painful Diabetic Peripheral Neuropathy
Han Na Jang, Tae Jung Oh
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Are herbal medicines alone or in combination for diabetic peripheral neuropathy more effective than methylcobalamin alone? A systematic review and meta-analysis
Chang-Woo Lee, Joon-Soo Jin, Seungwon Kwon, Chul Jin, Seung-Yeon Cho, Seong-Uk Park, Woo-Sang Jung, Sang-Kwan Moon, Jung-Mi Park, Chang-Nam Ko, Ki-Ho Cho
Complementary Therapies in Clinical Practice.2022; 49: 101657. CrossRef
Pathogenesis and Treatment of Diabetic Peripheral Neuropathy
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The Journal of Korean Diabetes.2022; 23(4): 222. CrossRef
Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015) (Diabetes Metab J 2021;45:115-9)
Seong-Su Moon, Chong Hwa Kim, Seon Mee Kang, Eun Sook Kim, Tae Jung Oh, Jae-Seung Yun, Ho Chan Cho, Dae Jung Kim, Tae Sun Park
Diabetes & Metabolism Journal.2021; 45(3): 459. CrossRef
Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015) (Diabetes Metab J 2021;45:115-9)
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Original Articles

Drug/Regimen
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

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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

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Estimating Type 2 Diabetes Prevalence: A Model of Drug Consumption Data
Rita Oliveira, Matilde Monteiro-Soares, José Pedro Guerreiro, Rúben Pereira, António Teixeira-Rodrigues
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Disease burden and symptom management in type 2 diabetic patients: A phenomenological study
Sevgi Demir Çam, Sevda Uzun
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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

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

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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.

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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
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Piaojian Yu, Wei Wang, Wanrong Guo, Lidan Cheng, Zhiping Wan, Yanglei Cheng, Yunfeng Shen, Fen Xu
Experimental and Clinical Endocrinology & Diabetes.2023; 131(11): 595. CrossRef
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
Evidence-Based Complementary and Alternative Medicine.2022; 2022: 1. 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
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
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Response

Response: Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus (Diabetes Metab J 2011;35:159-65): Soon Ae Kim, Woo Ho Shim, Eun Hae Lee, Young Mi Lee, Sun Hee Beom, Eun Sook Kim, Jeong Seon Yoo, Ji Sun Nam, Min Ho Cho, Jong Suk Park, Chul Woo Ahn, Kyung Rae Kim; Diabetes Metab J. 2011;35(3):300-301. Published online June 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.3.300

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Efficacy and Safety of Switching from Sitagliptin to Ipragliflozin in Obese Japanese Patients with Type 2 Diabetes Mellitus: A Single-Arm Multicenter Interventional Study
Kentaro Watanabe, Susumu Yamaguchi, Yoshinori Kosakai, Tetsuya Ioji, Hisamitsu Ishihara
Clinical Drug Investigation.2023; 43(12): 927. CrossRef

Original Article

Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus: Soon Ae Kim, Woo Ho Shim, Eun Hae Lee, Young Mi Lee, Sun Hee Beom, Eun Sook Kim, Jeong Seon Yoo, Ji Sun Nam, Min Ho Cho, Jong Suk Park, Chul Woo Ahn, Kyung Rae Kim; Diabetes Metab J. 2011;35(2):159-165. Published online April 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.2.159

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Background

Sitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects.

Methods

We obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (ΔHbA1c) and fasting plasma glucose (ΔFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in ΔHbA1c or >20% in ΔFPG levels at 24 weeks.

Results

We classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70±2.40 vs. 26.00±2.26, P≤0.01) and were younger (58.83±11.57 years vs. 62.87±12.09 years, P=0.03) than the non-responder group.

Conclusion

In Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders.

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Response

Response: Effects of Rosiglitazone on Inflammation in Otsuka Long-Evans Tokushima Fatty Rats (Korean Diabetes J 2010;34:191-9): Eun Sook Kim; Korean Diabetes J. 2010;34(4):263-264. Published online August 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.4.263

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Original Articles

Effects of Rosiglitazone on Inflammation in Otsuka Long-Evans Tokushima Fatty Rats: Jin Woo Lee, Il Seong Nam-Goong, Jae Geun Kim, Chang Ho Yun, Se Jin Kim, Jung Il Choi, Young IL Kim, Eun Sook Kim; Korean Diabetes J. 2010;34(3):191-199. Published online June 30, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.3.191

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Abstract PDF PubReader

Background

Inflammation plays a role in the response to metabolic stress in type 2 diabetes. However, the effects of rosiglitazone on inflammation of skeletal muscle have not been fully examined in type 2 diabetes.

Methods

We investigated the effects of the insulin-sensitizing anti-diabetic agent, rosiglitazone, on the progression of skeletal muscle inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) type 2 diabetic rats. We examined the expression of serologic markers (serum glucose, insulin and free fatty acid) and inflammatory cytokines (tumor-necrosis factor-α, interleukin [IL]-1β and IL-6) in OLETF rats from early to advanced diabetic stage (from 28 to 40 weeks of age).

Results

Serum glucose and insulin concentrations were significantly decreased in rosiglitazone-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone treatment significantly decreased the concentrations of serum inflammatory cytokines from 28 to 40 weeks of age. The mRNA expression of various cytokines in skeletal muscle was reduced in rosiglitazone-treated OLETF rats compared with untreated OLETF rats. Furthermore, rosiglitazone treatment resulted in the downregulation of ERK1/2 phosphorylation and NF-κB expression in the skeletal muscle of OLETF rats.

Conclusion

These results suggest that rosiglitazone may improve insulin sensitivity with its anti-inflammatory effects on skeletal muscle.

Citations

Citations to this article as recorded by

Rosiglitazone Elicits an Adiponectin-Mediated Insulin-Sensitizing Action at the Adipose Tissue-Liver Axis in Otsuka Long-Evans Tokushima Fatty Rats
Jia Li, Yao-Ming Xue, Bo Zhu, Yong-Hua Pan, Yan Zhang, Chunxia Wang, Yuhao Li
Journal of Diabetes Research.2018; 2018: 1. CrossRef
Sirt1 and Sirt6 Mediate Beneficial Effects of Rosiglitazone on Hepatic Lipid Accumulation
Soo Jin Yang, Jung Mook Choi, Eugene Chang, Sung Woo Park, Cheol-Young Park, Aimin Xu
PLoS ONE.2014; 9(8): e105456. CrossRef
Beneficial effects of co-enzyme Q10 and rosiglitazone in fructose-induced metabolic syndrome in rats
Suzan M. Mansour, Hala F. Zaki, Ezz-El-Din S. El-Denshary
Bulletin of Faculty of Pharmacy, Cairo University.2013; 51(1): 13. CrossRef
Chromium Picolinate and Rosiglitazone Improve Biochemical Derangement in a Rat Model of Insulin Resistance: Role of TNF-a and Leptin
Suzan M. Mansour, Hala F. Zaki, Ezz-El-Din El-Denshar
Pharmacologia.2013; 4(3): 186. CrossRef
Angiotensin Receptor Blockade Increases Pancreatic Insulin Secretion and Decreases Glucose Intolerance during Glucose Supplementation in a Model of Metabolic Syndrome
Ruben Rodriguez, Jose A. Viscarra, Jacqueline N. Minas, Daisuke Nakano, Akira Nishiyama, Rudy M. Ortiz
Endocrinology.2012; 153(4): 1684. CrossRef
Rodent Models for Metabolic Syndrome Research
Sunil K. Panchal, Lindsay Brown, Andrea Vecchione
BioMed Research International.2011;[Epub] CrossRef
Letter: Effects of Rosiglitazone on Inflammation in Otsuka Long-Evans Tokushima Fatty Rats (Korean Diabetes J 2010;34:191-9)
Soo Jin Yang, Cheol-Young Park
Korean Diabetes Journal.2010; 34(4): 261. CrossRef

The Role of Hypothalamic FoxO1 on Hyperphagia in Streptozotocin-Induced Diabetic Mice.: Il Seong Nam-Goong, Jae Geun Kim, Se Jin Kim, Seong Jae Hur, Jin Woo Lee, Eun Sook Kim, Chang Ho Yun, Byung Ju Lee, Young Il Kim; Korean Diabetes J. 2009;33(5):375-381. Published online October 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.5.375

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Abstract PDF: BACKGROUND
Streptozotocin-induced diabetic animals are characterized by hyperphagia due to deficiencies of insulin and leptin. Forkhead box-containing protein of the O subfamily-1 (FoxO1) regulates energy homeostasis by regulating energy expenditure and food intake as well as mediating insulin and leptin signals in the hypothalamus. To identify the mediator of diabetic hyperphagia, we examined the effects of insulin or leptin on hypothalamic FoxO1 expression in a diabetic animal model. METHODS: Diabetes was induced in mice (C57BL/6) by intraperitoneal administration of streptozotocin (200 mg/kg). Stainless steel cannula was implanted into the lateral ventricle of the brain in each mouse. After three weeks, the mice were administered saline, insulin or leptin via intracerebroventricular (ICV) route. The medial hypothalamus was isolated to evaluate the mRNA expressions of FoxO1 and neuropeptides. RESULTS: Streptozotocin-induced diabetic mice exhibited significant elevations of blood glucose and food intake and significantly low levels of serum insulin and leptin. The levels of hypothalamic FoxO1 mRNA were significantly increased in diabetic mice. The hypothalamic expression of neuropeptide Y (NPY) mRNA was increased, but the expression of preproopiomelanocortin (POMC) mRNA was decreased in diabetic mice. ICV administration of insulin or leptin attenuated the upregulation of hypothalamic FoxO1 mRNA, and resulted in downregulation of NPY mRNA and upregulation of POMC mRNA in diabetic mice. CONCLUSION: We observed that the expression of hypothalamic FoxO1 mRNA was increased in streptozotocin-induced diabetic mice, and that it was significantly attenuated by central administration of insulin or leptin. These results suggest that hypothalamic FoxO1 is the direct mediator of diabetic hyperphagia.

Cystatin C is a Valuable Marker for Predicting Future Cardiovascular Diseases in Type 2 Diabetic Patients.: Seung Hwan Lee, Kang Woo Lee, Eun Sook Kim, Ye Ree Park, Hun Sung Kim, Shin Ae Park, Mi Ja Kang, Yu Bai Ahn, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Hyuk Sang Kwon; Korean Diabetes J. 2008;32(6):488-497. Published online December 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.6.488

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Abstract PDF

BACKGROUND
Recent studies suggest that serum Cystatin C is both a sensitive marker for renal dysfunction and a predictive marker for cardiovascular diseases. We aimed to evaluate the association between Cystatin C and various biomarkers and to find out its utility in estimating risk for cardiovascular diseases in type 2 diabetic patients. METHODS: From June 2006 to March 2008, anthropometric measurements and biochemical studies including biomarkers for risk factors of cardiovascular diseases were done in 520 type 2 diabetic patients. A 10-year risk for coronary heart diseases and stroke was estimated using Framingham risk score and UKPDS risk engine. RESULTS: The independent variables showing statistically significant associations with Cystatin C were age (beta = 0.009, P < 0.0001), hemoglobin (beta = -0.038, P = 0.0006), serum creatinine (beta = 0.719, beta < 0.0001), uric acid (beta = 0.048, P = 0.0004), log hsCRP (beta = 0.035, P = 0.0021) and homocysteine (beta = 0.005, P = 0.0228). The levels of microalbuminuria, carotid intima-media thickness, fibrinogen and lipoprotein (a) also correlated with Cystatin C, although the significance was lost after multivariate adjustment. Calculated risk for coronary heart diseases increased in proportion to Cystatin C quartiles: 3.3 +/- 0.4, 6.2 +/- 0.6, 7.6 +/- 0.7, 8.4 +/- 0.7% from Framingham risk score (P < 0.0001); 13.1 +/- 0.9, 21.2 +/- 1.6, 26.1 +/- 1.7, 35.4 +/- 2.0% from UKPDS risk engine (P < 0.0001) (means +/- SE). CONCLUSIONS: Cystatin C is significantly correlated with various emerging biomarkers for cardiovascular diseases. It was also in accordance with the calculated risk for cardiovascular diseases. These findings verify Cystatin C as a valuable and useful marker for predicting future cardiovascular diseases in type 2 diabetic patients.

Citations

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Lack of Association between Serum Cystatin C Levels and Coronary Artery Disease in Diabetic Patients
Eun Hee Kim, Ji Hee Yu, Sang Ah Lee, Eui Young Kim, Won Gu Kim, Seung Hun Lee, Eun Hee Cho, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Ki-Up Lee
Korean Diabetes Journal.2010; 34(2): 95. CrossRef
Insulin resistance and inflammation may have an additional role in the link between cystatin C and cardiovascular disease in type 2 diabetes mellitus patients
Seung-Hwan Lee, Shin-Ae Park, Seung-Hyun Ko, Hyeon-Woo Yim, Yu-Bae Ahn, Kun-Ho Yoon, Bong-Yun Cha, Ho-Young Son, Hyuk-Sang Kwon
Metabolism.2010; 59(2): 241. CrossRef

Clustering of Risk Variables in Insulin Resistance Syndrome in Jungup District, Korea.: Sang Wook Kim, Myung Hoe Huh, Young Il Kim, Jin Yub Kim, Eun Sook Kim, Moo Song Lee, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee; Korean Diabetes J. 1999;23(6):843-856. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Insulin resistance syndrome (IRS), a clustering of hypertension, impaired glucose tolerance, low HDL cholesterol and high triglyceride, is prevalent in Korea. We studied the correlational structure of IRS using factor analysis to evaluate whether a single process underlies in the clustering of these risk factors. METHODS: Factor analysis was performed using data from 1,018 non-diabetic subjects (388 men and 630 women) who participated in the Jungup epidemiological study. RESULTS: Factor analysis reduced 9 correlated risk factors to 4 independent factors, each reflecting a different aspect of IRS: hypertension factor (increased systolic and diastolic blood pressure), glucose intolerance factor (increased fasting and postload glucose), obesity factor (increased body mass index, waist circumference, and increased insulin), and dyslipidemia factor (increased trigly- cerides and decreased HDL cholesterol). Increased insulin was also loaded into dyslipidemia factor in men and glucose intolerance factor in women. These factors explained about 70% of the total variance in the data. Three factors such as the glucose intolerance factor, the dyslipidemia factor and the obesity factor, were linked through mutual association with hyperinsulinemia, while hypertension factor was not associated with hyperin- sulinemia. Age-adjusted mean BP by BMI tertile and fasting insulin level tertile for men and women increased progressively with increase in BMI in men and women. There was no significant elevation of mean BP according to increase in fasting insulin level. In contrast to premenopausal women in whom hyperinsulinemia show mutual association with the glucose intolerance factor, the dyslipidemia factor, and the obesity factor, hyperinsulinemia was only loaded into obesity factor in postmenopausal women. CONCLUSION: These results suggested that more than one process underlies the clustering of IRS. In sulin resistance alone did not seem to be the single underlying mechanism of IRS. Especially, hypertension was not correlated with hyperin- sulinemia.

Lack of Effectiveness of Glomerular Hyperfiltration on Development of Microalbuminuria in Type 2 Diabetic Patients: five Year Follow-up Study.: Eun Sook Kim, Sang Wook Kim, Jin Yub Kim, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee; Korean Diabetes J. 1999;23(2):155-161. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Glomerular hyperfiltration (GHF) is found in 30-40% of patients with type 1 diabetes at the onset of the disease. Several lines of evidence suggest that this might be responsible for the development of diabetic nephropathy. However, it is still controversial whether GHF is a risk factor in patients with type 2 diabetes. This led us to perform a five-year-prospective study in normoalbuminuric type 2 diabetic patients. METHODS: A total of 68 patients with type 2 diabetes were studied prospectively, They were all normoalbuminuric initially. Glomerular filtration rate was determined by the 51Cr-EDTA single injection method and urinary albumin excretion rate by the radioimtnunoassay method. RESULTS: GHF was present in 19 out of 68 patients. At follow-up, l7 out of 49 patients of the normofiltration group and 3 out of 19 patients of GHF group progressed to microalbuminuria (p>0.05). Multiple logistic regression analysis revealed that the known duration of diabetes, systolic hypertension, and the presence of retinopathy were independently associated with the development of microalbuminuria. CONCLUSION: Our study suggests that GHF does not predict the subsequent development of diabetic nephropathy as indicated by the elevation of the urinary albumin excretion rate during the five year interval.

Microalbuminuria in Diabetic and Non-diabetic Subjects: A population Based Study.: Young Il Kim, Yun Ey Chung, Jin Yup Kim, Sang Wook Kim, Eun Sook Kim, Moo Song Lee, Joong Yeoul Park, Sung Kwan Hong, Ki Up Lee; Korean Diabetes J. 1999;23(1):79-86. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Microalbuminuria is associated with increased cardiovascular mortality in type 2 diabetic patients and non-diabetic subjects. This study was undertaken to determine the prevalence ot microalbuminuria among diabetic and non-diabetic subjects in Korea and to determine the factors associated with microalbuminuria. METHOD: A sample of 1,791 subjects aged > 40 years living in Jungup district were selected from the 28,380 inhabitants using a random cluster sampling method. Among these subjects, 1,006 of them (56.1%) underwent the 75 g oral glucose tolerance test that was also part of the timed overnight urine collection. 46 subjects were excluded because they had signs of urinary tract infection (n=41) or overt proteinuria (n=5). Microalbuminuria was defined as urinary albumin excretion rate (UAER) between 20 and 200 pg/min. RESULTS: Subjects with microalbuminuria had a higher weight and body mass index (BMI), abdominal circumference, systolic and diastolic blood pressure (BP), fasting and 2hr plasma glucose, fasting semm insulin and proinsulin concentrations than subjects without microalbuminuria. The prevalence of micro- albuminuria increased as the glucose tolerance worsened[6.0% in normal glucose tolerance, 11.8% in impaired glucose tolerance (IGT) and 21.8% in diabetes, respectively; x trend=25.9, p<0.(0001]. Mean UAER of subjects with hypertension was greater than that of subjects without hypertension (7.8+0.9ug/min vs. 9.6+0.7ug/min, p<0.001). Univariate analysis revealed that the UAER was significantly (p<0.05) correlated with weight and BMI, abdominal circumference, systolic and diastolic BP, fasting and 2hr plasma glucose, fasting serum insulin and proinsulin after sex-adjustment. Multiple regression analysis revealed that weight or BMI, diastolic BP, 2hr plasma glucose and fasting serum insulin were independently associated with UAER in non-diabetic subjects. CONCLUSION: The present study demonstrates that the prevalence of microalburninuria is higher in patients with glucose intolerance. The association of the UAER with BMI, diastolic BP, 2hr plasma glucose and fasting serum insulin suggest that microalbuminuria is a feature of the insulin resistance syndrome.

Prevalence of Insulin Resistance Syndrome in Subjects Living in Jungup District , Korea.: Sang Wook Kim, Jin Yub Kim, Eun Sook Kim, Young Il Kim, Moo Song Lee, Hyeong Ho Kim, Joong Yeoul Park, Sung Kwan Hong, Ki Up Lee; Korean Diabetes J. 1999;23(1):70-78. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The clustering of hypertension, impaired glucose tolerance, low HDL cholesteml and high triglyceride is known as insulin resistance syndrome (IRS). We studied the prevalence of insulin resistance syndrome among subjects living in Jungup district, Korea. METHODS: Among a total of 151,000 subjects over 40 years of years living in Jungup district, a sample of 1,791 was selected using a random cluster sampling method. Oral glucose tolerance test revealed 1,018 subjects with normal or impaired glucose tolerance. The IRS was defined as the coexistence of two or more components of triad; hypertension, impaired glucose tolerance and dyslipidemia (triglycerides >= 200mg/dL and HDL <45 mg/dL for woman, HDL < 35 mg/dL for men). RESULTS: Twenty-one percent of men and 45% of women were obese and 50.8% and 61.9% were hypertensive. Eleven percent of men and 16 percent of women were found to have dyslipidemia. The prevalence of impaired glucose tolerance was 10.2% for men and 15.7% for women. The prevalence of IRS in the Jungup population was 12.8% for men and 19.6% for women. The prevalence of IRS increased according to the plasma level of insulin. There was a positive correlation between the number of components of IRS and the level of fasting plasma insulin. CONCLUSION: We conclude that the prevalence of IRS is high in Korean subjects. The close correlation between the IRS components and fasting insulin level suggests that cardiovascular risk is associated with insulin resistance.

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