- Clinical Diabetes & Therapeutics
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- Asian Subpopulations May Exhibit Greater Cardiovascular Benefit from Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A Meta-Analysis of Cardiovascular Outcome Trials
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Yu Mi Kang, Yun Kyung Cho, Jiwoo Lee, Seung Eun Lee, Woo Je Lee, Joong-Yeol Park, Ye-Jee Kim, Chang Hee Jung, Michael A. Nauck
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Diabetes Metab J. 2019;43(4):410-421. Published online December 27, 2018
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DOI: https://doi.org/10.4093/dmj.2018.0070
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- Background
Based on reported results of three large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), we aimed to investigate the overall effect of GLP-1 RAs on major adverse cardiovascular events (MACEs) and to identify subpopulations exhibiting the greatest cardiovascular (CV) benefit. MethodsThree CVOTs reporting effects of long-acting GLP-1 RAs were included: LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide once weekly). In all studies, the primary endpoint was three-point MACE, comprising CV death, non-fatal myocardial infarction, and non-fatal stroke. Overall effect estimates were calculated as hazard ratios and 95% confidence intervals (CIs) using the random-effects model; subgroup analyses reported in the original studies were similarly analyzed. ResultsOverall, statistically significant risk reductions in MACE and CV death were observed. Subgroup analysis indicated a significant racial difference with respect to CV benefit (P for interaction <0.001), and more substantial risk reductions were observed in subjects of African origin (relative risk [RR], 0.78; 95% CI, 0.60 to 0.99) and in Asians (RR, 0.35; 95% CI, 0.09 to 1.32). However, post hoc analysis (Bonferroni method) revealed that only Asians exhibited a significantly greater CV benefit from treatment, compared with white subjects (P<0.0001). ConclusionLong-acting GLP-1 RAs reduced risks of MACE and CV deaths in high-risk patients with type 2 diabetes mellitus. Our findings of a particularly effective reduction in CV events with GLP-1 RA in Asian populations merits further exploration and dedicated trials in specific populations.
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- Safety and Effectiveness of Dulaglutide in the Treatment of Type 2 Diabetes Mellitus: A Korean Real-World Post-Marketing Study
Jeonghee Han, Woo Je Lee, Kyu Yeon Hur, Jae Hyoung Cho, Byung Wan Lee, Cheol-Young Park Diabetes & Metabolism Journal.2024; 48(3): 418. CrossRef - Sex, racial, ethnic, and geographical disparities in major adverse cardiovascular outcome of glucagon-like peptide-1 receptor agonists among patients with and without diabetes mellitus: A meta-analysis of placebo-controlled randomized controlled trials
Frederick Berro Rivera, Nathan Ross B. Bantayan, John Paul Aparece, Linnaeus Louisse A. Cruz, John Vincent Magallong, Polyn Luz Pine, Anne Mira Nicca Idian-Javier, Grace Nooriza O. Lumbang, Edgar V. Lerma, Kyla M. Lara-Breitinger, Martha Gulati, Krishnasw Journal of Clinical Lipidology.2024; 18(4): e588. CrossRef - A randomized, double‐blind trial assessing the efficacy and safety of two doses of dulaglutide in Japanese participants with type 2 diabetes (AWARD‐JPN)
Tomoaki Morioka, Masakazu Takeuchi, Akichika Ozeki, Masanori Emoto Diabetes, Obesity and Metabolism.2024; 26(8): 3167. CrossRef - Coronary Artery Disease in South Asian Patients: Cardiovascular Risk Factors, Pathogenesis and Treatments
Vincenzo Sucato, Giuseppe Coppola, Girolamo Manno, Giuseppe Vadalà, Giuseppina Novo, Egle Corrado, Alfredo Ruggero Galassi Current Problems in Cardiology.2023; 48(8): 101228. CrossRef - Retrospective Analysis of the Effectiveness of Oral Semaglutide in Type 2 Diabetes Mellitus and Its Effect on Cardiometabolic Parameters in Japanese Clinical Settings
Hodaka Yamada, Masashi Yoshida, Shunsuke Funazaki, Jun Morimoto, Shiori Tonezawa, Asuka Takahashi, Shuichi Nagashima, Kimura Masahiko, Otsuka Kiyoshi, Kazuo Hara Journal of Cardiovascular Development and Disease.2023; 10(4): 176. CrossRef - Efficacy of treatment with glucagon-like peptide receptor agonists-1 in Asian patients with type 2 diabetes mellitus
L. Yu. Khamnueva, L. S. Andreeva Problems of Endocrinology.2023; 69(2): 38. CrossRef - Role of diabetes in stroke: Recent advances in pathophysiology and clinical management
Sian A. Bradley, Kevin J. Spring, Roy G. Beran, Dimitrios Chatzis, Murray C. Killingsworth, Sonu M. M. Bhaskar Diabetes/Metabolism Research and Reviews.2022;[Epub] CrossRef - Obesity Pillars Roundtable: Obesity and East Asians
Harold Edward Bays, Jennifer Ng, Jeffrey Sicat, Michelle Look Obesity Pillars.2022; 2: 100011. CrossRef - Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations
Calvin Ke, K. M. Venkat Narayan, Juliana C. N. Chan, Prabhat Jha, Baiju R. Shah Nature Reviews Endocrinology.2022; 18(7): 413. CrossRef - Effect of race on cardiometabolic responses to once-weekly exenatide: insights from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL)
Timothy M. E. Davis, Anna Giczewska, Yuliya Lokhnygina, Robert J. Mentz, Naveed Sattar, Rury R. Holman Cardiovascular Diabetology.2022;[Epub] CrossRef - Generalizability of the Results of Cardiovascular Outcome Trials of Glucagon-Like Peptide 1 Receptor Agonists in Chinese Patients with Type 2 Diabetes Mellitus
Xiaoling Cai, Linong Ji Diabetes Therapy.2021; 12(7): 1861. CrossRef - Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes
Jae-Seung Yun, Seung-Hyun Ko Metabolism.2021; 123: 154838. CrossRef - Sex and ethnic differences in the cardiovascular complications of type 2 diabetes
Jian L. Yeo, Emer M. Brady, Gerry P. McCann, Gaurav S. Gulsin Therapeutic Advances in Endocrinology and Metabolism.2021; 12: 204201882110342. CrossRef - Efficacy and Safety of GLP-1 Receptor Agonists in Patients With Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
Yuan Zhu, Jiao Xu, Dong Zhang, Xingyu Mu, Yi Shi, Shangtao Chen, Zengxiang Wu, Shuangqing Li Frontiers in Endocrinology.2021;[Epub] CrossRef - Efficacy and safety of dulaglutide in type 2 diabetes patients in endocrinology clinics of Islamabad, Pakistan
Matiullah Kamin, SajjadAli Khan, UmarYousaf Raja, Osama Ishtiaq, Asmara Malik, Tejhmal Rehman, MuhammadUmar Wahab Indian Journal of Endocrinology and Metabolism.2021; 25(5): 456. CrossRef - Type 2 Diabetes and Atherosclerotic Cardiovascular Disease in South Asians: a Unique Population with a Growing Challenge
Afreen I. Shariff, Nitya Kumar, William S. Yancy, Leonor Corsino Current Diabetes Reports.2020;[Epub] CrossRef - Antihypertensive and Renal Mechanisms of SGLT2 (Sodium-Glucose Linked Transporter 2) Inhibitors
Christopher S. Wilcox Hypertension.2020; 75(4): 894. CrossRef - Subpopulation Differences in the Cardiovascular Efficacy of Long-Acting Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis
Liyun He, Na Yang, Lingling Xu, Fan Ping, Wei Li, Yuxiu Li, Huabing Zhang Diabetes Therapy.2020; 11(9): 2121. CrossRef - 2020 Consensus of Taiwan Society of Cardiology on the pharmacological management of patients with type 2 diabetes and cardiovascular diseases
Chern-En Chiang, Kwo-Chang Ueng, Ting-Hsing Chao, Tsung-Hsien Lin, Yih-Jer Wu, Kang-Ling Wang, Shih-Hsien Sung, Hung-I Yeh, Yi-Heng Li, Ping-Yen Liu, Kuan-Cheng Chang, Kou-Gi Shyu, Jin-Long Huang, Cheng-Dao Tsai, Huei-Fong Hung, Ming-En Liu, Tze-Fan Chao, Journal of the Chinese Medical Association.2020; 83(7): 587. CrossRef - Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease
Kyung-Soo Kim, Byung-Wan Lee Clinical and Molecular Hepatology.2020; 26(4): 430. CrossRef
- Clinical Diabetes & Therapeutics
- Effectiveness and Safety of Adding Basal Insulin Glargine in Patients with Type 2 Diabetes Mellitus Exhibiting Inadequate Response to Metformin and DPP-4 Inhibitors with or without Sulfonylurea
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Yu Mi Kang, Chang Hee Jung, Seung-Hwan Lee, Sang-Wook Kim, Kee-Ho Song, Sin Gon Kim, Jae Hyeon Kim, Young Min Cho, Tae Sun Park, Bon Jeong Ku, Gwanpyo Koh, Dol Mi Kim, Byung-Wan Lee, Joong-Yeol Park
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Diabetes Metab J. 2019;43(4):432-446. Published online June 19, 2019
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DOI: https://doi.org/10.4093/dmj.2018.0092
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- Background
We aimed to investigate the effectiveness and safety of adding basal insulin to initiating dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin and/or sulfonylurea (SU) in achieving the target glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM). MethodsThis was a single-arm, multicenter, 24-week, open-label, phase 4 study in patients with inadequately controlled (HbA1c ≥7.5%) T2DM despite the use of DPP-4 inhibitor and metformin. A total of 108 patients received insulin glargine while continuing oral antidiabetic drugs (OADs). The primary efficacy endpoint was the percentage of subjects achieving HbA1c ≤7.0%. Other glycemic profiles were also evaluated, and the safety endpoints were adverse events (AEs) and hypoglycemia. ResultsThe median HbA1c at baseline (8.9%; range, 7.5% to 11.1%) decreased to 7.6% (5.5% to 11.7%) at 24 weeks. Overall, 31.7% subjects (n=33) achieved the target HbA1c level of ≤7.0%. The mean differences in body weight and fasting plasma glucose were 1.2±3.4 kg and 56.0±49.8 mg/dL, respectively. Hypoglycemia was reported in 36 subjects (33.3%, 112 episodes), all of which were fully recovered. There was no serious AE attributed to insulin glargine. Body weight change was significantly different between SU users and nonusers (1.5±2.5 kg vs. −0.9±6.0 kg, P=0.011). ConclusionThe combination add-on therapy of insulin glargine, on metformin and DPP-4 inhibitors with or without SU was safe and efficient in reducing HbA1c levels and thus, is a preferable option in managing T2DM patients exhibiting dysglycemia despite the use of OADs.
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- 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 - Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease
Kyung-Soo Kim, Byung-Wan Lee Clinical and Molecular Hepatology.2020; 26(4): 430. CrossRef
- Pathophysiology
- Role of NO/VASP Signaling Pathway against Obesity-Related Inflammation and Insulin Resistance
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Yu Mi Kang, Francis Kim, Woo Je Lee
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Diabetes Metab J. 2017;41(2):89-95. Published online November 15, 2016
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DOI: https://doi.org/10.4093/dmj.2017.41.2.89
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Obesity has quickly become a worldwide pandemic, causing major adverse health outcomes such as dyslipidemia, type 2 diabetes mellitus, cardiovascular disease and cancers. Obesity-induced insulin resistance is the key for developing these metabolic disorders, and investigation to understand the molecular mechanisms involved has been vibrant for the past few decades. Of these, low-grade chronic inflammation is suggested as a critical concept in the development of obesity-induced insulin resistance, and the anti-inflammatory effect of nitric oxide (NO) signaling has been reported to be linked to improvement of insulin resistance in multiple organs involved in glucose metabolism. Recently, a body of evidence suggested that vasodilatory-stimulated phosphoprotein (VASP), a downstream mediator of NO signaling plays a crucial role in the anti-inflammatory effect and improvement of peripheral insulin resistance. These preclinical studies suggest that NO/VASP signaling could be an ideal therapeutic target in the treatment of obesity-related metabolic dysfunction. In this review, we introduce studies that investigated the protective role of NO/VASP signaling against obesity-related inflammation and insulin resistance in various tissues.
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- Hippocampal proteomic changes in high-fat diet-induced obese mice associated with memory decline
Ping Lu, Cun-Xiu Gao, Fei-Jian Luo, Yu-Ting Huang, Mei-Mei Gao, Yue-Sheng Long The Journal of Nutritional Biochemistry.2024; 125: 109554. CrossRef - Gases and gas-releasing materials for the treatment of chronic diabetic wounds
Shuming Ye, Neng Jin, Nan Liu, Feixiang Cheng, Liang Hu, Guiyang Zhang, Qi Li, Juehua Jing Biomaterials Science.2024; 12(13): 3273. CrossRef - Leptina, obesidad y enfermedades cardiovasculares
Jorly Mejia-Montilla , Nadia Reyna-Villasmil, Andreina Fernández-Ramírez, Eduardo Reyna-Villasmil Revista Repertorio de Medicina y Cirugía.2023; 32(3): 218. CrossRef - Urinary and circulatory netrin-1 as biomarker in diabetes and its related complications: a systematic review and meta-analysis
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Chad D. Schwartzkopf, John R. Hadcock, Guang Liu, Peter Germano, Julien Roux, Courtney M. Shea, Emmanuel S. Buys, Juli E. Jones Frontiers in Pharmacology.2022;[Epub] CrossRef - Type 2 Diabetes Complicated With Heart Failure: Research on Therapeutic Mechanism and Potential Drug Development Based on Insulin Signaling Pathway
Hui Ye, Yanan He, Chuan Zheng, Fang Wang, Ming Yang, Junzhi Lin, Runchun Xu, Dingkun Zhang Frontiers in Pharmacology.2022;[Epub] CrossRef - Effect of low-dose tadalafil once daily on glycemic control in patients with type 2 diabetes and erectile dysfunction: a randomized, double-blind, placebo-controlled pilot study
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Yingzheng Zhao, Lanzi Luo, Lantian Huang, Yingying Zhang, Mengqi Tong, Hanxiao Pan, Jianxun Shangguan, Qing Yao, Shihao Xu, Helin Xu Journal of Controlled Release.2022; 350: 93. CrossRef - Amelioration effect of black seed oil against high‐fat diet‐induced obesity in rats through Nrf2/HO‐1 pathway
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John P. Hanrahan, Jelena P. Seferovic, James D. Wakefield, Phebe J. Wilson, Jennifer G. Chickering, Joon Jung, Kenneth E. Carlson, Daniel P. Zimmer, Andrew L. Frelinger, Alan D. Michelson, Linda Morrow, Michael Hall, Mark G. Currie, G. Todd Milne, Albert Diabetologia.2020; 63(4): 733. CrossRef - Advantages of Phosphodiesterase Type 5 Inhibitors in the Management of Glucose Metabolism Disorders: A Clinical and Translational Issue
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Andras Franko, Marketa Kovarova, Susanne Feil, Robert Feil, Robert Wagner, Martin Heni, Alfred Königsrainer, Marc Ruoß, Andreas K. Nüssler, Cora Weigert, Hans-Ulrich Häring, Stefan Z. Lutz, Andreas Peter Metabolism.2018; 88: 22. CrossRef
- Serum Ceruloplasmin Level as a Predictor for the Progression of Diabetic Nephropathy in Korean Men with Type 2 Diabetes Mellitus
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Min Jung Lee, Chang Hee Jung, Yu Mi Kang, Jung Eun Jang, Jaechan Leem, Joong-Yeol Park, Woo Je Lee
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Diabetes Metab J. 2015;39(3):230-239. Published online April 22, 2015
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DOI: https://doi.org/10.4093/dmj.2015.39.3.230
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- Background
Oxidative stress is known to be associated with progression of diabetic kidney disease. Ceruloplasmin acts as a pro-oxidant under conditions of severe oxidative stress. Thus, we conducted a longitudinal observational study to evaluate whether the serum ceruloplasmin level is a predictive biomarker for progression of diabetic nephropathy. MethodsA total of 643 Korean men with type 2 diabetes mellitus were enrolled. Serum ceruloplasmin was measured using a nephelometric method. Progression of diabetic nephropathy was defined as transition in albuminuria class (i.e., normoalbuminuria to microalbuminuria, microalbuminuria to macroalbuminuria, or normoalbuminuria to macroalbuminuria) and/or a greater than 2-fold increase of serum creatinine at follow-up compared with the baseline value. ResultsDuring the follow-up period (median, 2.7 years; range, 0.3 to 4.4 years), 49 of 643 patients (7.6%) showed the progression of diabetic nephropathy and three patients (0.5%) developed end-stage renal disease. Baseline ceruloplasmin levels were higher in the progressors than in the nonprogressors (262.6±40.9 mg/L vs. 233.3±37.8 mg/L, P<0.001). Kaplan-Meier analysis showed a significantly higher incidence of nephropathy progression according to ceruloplasmin tertile (log-rank test, P<0.001). The hazard ratio (HR) for progression of diabetic nephropathy was significantly higher in the highest ceruloplasmin tertile category compared with the lowest ceruloplasmin tertile category, even after adjusting for confounding variables (HR, 3.32; 95% confidence interval, 1.28 to 8.61; P=0.003). ConclusionBaseline serum ceruloplasmin is an independent predictive factor for the progression of diabetic nephropathy in patients with type 2 diabetes mellitus.
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