- Drug/Regimen
- Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study
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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
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Diabetes Metab J. 2021;45(5):675-683. Published online August 12, 2020
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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.
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Citations
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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
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- Pathophysiology
- Mitochondrial Dysfunction in Adipocytes as a Primary Cause of Adipose Tissue Inflammation
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Chang-Yun Woo, Jung Eun Jang, Seung Eun Lee, Eun Hee Koh, Ki-Up Lee
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Diabetes Metab J. 2019;43(3):247-256. Published online March 27, 2019
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DOI: https://doi.org/10.4093/dmj.2018.0221
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Abstract
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Adipose tissue inflammation is considered a major contributing factor in the development of obesity-associated insulin resistance and cardiovascular diseases. However, the cause of adipose tissue inflammation is presently unclear. The role of mitochondria in white adipocytes has long been neglected because of their low abundance. However, recent evidence suggests that mitochondria are essential for maintaining metabolic homeostasis in white adipocytes. In a series of recent studies, we found that mitochondrial function in white adipocytes is essential to the synthesis of adiponectin, which is the most abundant adipokine synthesized from adipocytes, with many favorable effects on metabolism, including improvement of insulin sensitivity and reduction of atherosclerotic processes and systemic inflammation. From these results, we propose a new hypothesis that mitochondrial dysfunction in adipocytes is a primary cause of adipose tissue inflammation and compared this hypothesis with a prevailing concept that “adipose tissue hypoxia” may underlie adipose tissue dysfunction in obesity. Recent studies have emphasized the role of the mitochondrial quality control mechanism in maintaining mitochondrial function. Future studies are warranted to test whether an inadequate mitochondrial quality control mechanism is responsible for mitochondrial dysfunction in adipocytes and adipose tissue inflammation.
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- Obesity and Metabolic Syndrome
- Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice
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Han-Sol Park, Jung Eun Jang, Myoung Seok Ko, Sung Hoon Woo, Bum Joong Kim, Hyun Sik Kim, Hye Sun Park, In-Sun Park, Eun Hee Koh, Ki-Up Lee
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Diabetes Metab J. 2016;40(5):376-385. Published online April 5, 2016
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DOI: https://doi.org/10.4093/dmj.2016.40.5.376
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- Background
Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown. MethodsSeven-week-old C57BL/6J mice were given normal chow or a methionine- and choline-deficient diet (MCDD) with or without various statins, fluvastatin, pravastatin, simvastatin, atorvastatin, and rosuvastatin (15 mg/kg/day), for 6 weeks. Histological lesions were analyzed by grading and staging systems of NASH. We also measured mitochondrial and peroxisomal FAO in the liver. ResultsStatin treatment prevented the development of MCDD-induced NASH. Both steatosis and inflammation or fibrosis grades were significantly improved by statins compared with MCDD-fed mice. Gene expression levels of peroxisomal proliferator-activated receptor α (PPARα) were decreased by MCDD and recovered by statin treatment. MCDD-induced suppression of mitochondrial and peroxisomal FAO was restored by statins. Each statin's effect on increasing FAO and improving NASH was independent on its effect of decreasing cholesterol levels. ConclusionStatins prevented NASH and increased mitochondrial and peroxisomal FAO via induction of PPARα. The ability to increase hepatic FAO is likely the major determinant of NASH prevention by statins. Improvement of peroxisomal function by statins may contribute to the prevention of NASH.
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E. Matthew Morris, Colin S. McCoin, Julie A. Allen, Michelle L. Gastecki, Lauren G. Koch, Steven L. Britton, Justin A. Fletcher, Xiarong Fu, Wen‐Xing Ding, Shawn C. Burgess, R. Scott Rector, John P. Thyfault The Journal of Physiology.2017; 595(14): 4909. CrossRef - Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current Views and Prospects
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- Complications
- Serum Total Bilirubin Levels Provide Additive Risk Information over the Framingham Risk Score for Identifying Asymptomatic Diabetic Patients at Higher Risk for Coronary Artery Stenosis
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Jaechan Leem, Eun Hee Koh, Jung Eun Jang, Chang-Yun Woo, Jin Sun Oh, Min Jung Lee, Joon-Won Kang, Tae-Hwan Lim, Chang Hee Jung, Woo Je Lee, Joong-Yeol Park, Ki-Up Lee
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Diabetes Metab J. 2015;39(5):414-423. Published online October 22, 2015
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DOI: https://doi.org/10.4093/dmj.2015.39.5.414
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Abstract
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- Background
The diagnosis of coronary artery disease (CAD) is often delayed in patients with type 2 diabetes. Serum total bilirubin levels are inversely associated with CAD. However, no studies have examined whether this can be used as a biochemical marker for identifying asymptomatic diabetic patients at higher risk for having obstructive CAD. MethodsWe performed a cross-sectional study of 460 consecutive asymptomatic patients with type 2 diabetes. All patients underwent coronary computed tomographic angiography, and their serum total bilirubin levels were measured. Obstructive CAD was defined as ≥50% diameter stenosis in at least one coronary artery. ResultsSerum total bilirubin tertiles showed an inverse association with the prevalence of obstructive CAD. In multivariate logistic regression analysis, the odds ratio for the highest versus the lowest tertile of total bilirubin was 0.227 (95% confidence interval [CI], 0.130 to 0.398), and an increment of 1 µmol/L in serum total bilirubin level was associated with a 14.6% decrease in obstructive CAD after adjustment for confounding variables. Receiver operating characteristic curve analysis showed that the area under the curve for the Framingham Risk Score (FRS) plus serum total bilirubin level was 0.712 (95% CI, 0.668 to 0.753), which is significantly greater than that of the FRS alone (P=0.0028). ConclusionSerum total bilirubin level is inversely associated with obstructive CAD and provides additive risk information over the FRS. Serum total bilirubin may be helpful for identifying asymptomatic patients with type 2 diabetes who are at higher risk for obstructive CAD.
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- Association between bilirubin and biomarkers of metabolic health and oxidative stress in the MARK-AGE cohort
Vanessa Schoissengeier, Lina Maqboul, Daniela Weber, Tilman Grune, Alexander Bürkle, Maria Moreno-Villaneuva, Claudio Franceschi, Miriam Capri, Jürgen Bernhard, Olivier Toussaint, Florence Debacq-Chainiaux, Birgit Weinberger, Efstathios S. Gonos, Ewa Siko iScience.2024; 27(7): 110234. CrossRef - Nanoparticle-driven biosensors for diagnosis of viral hepatitis
Chenggong Zhu, Zhen Xun, Ruijie Fu, Qunfang Huang, Qishui Ou, Yunlei Xianyu, Can Liu TrAC Trends in Analytical Chemistry.2024; 180: 117985. CrossRef - DECREASE IN SERUM BILIRUBIN AS AN UNFAVORABLE MARKER OF CARDIOVASCULAR DISORDERS
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A. S. Akselrod, D. Yu. Shchekochikhin, E. S. Tebenkova, A. V. Zhelankin, D. A. Stonogina, E. A. Syrkina, S. K. Ternovoy Kardiologiya i serdechno-sosudistaya khirurgiya.2019; 12(5): 418. CrossRef - Pharmacological actions and therapeutic potentials of bilirubin in islet transplantation for the treatment of diabetes
Qing Yao, Xue Jiang, Longfa Kou, Adelaide T. Samuriwo, He-Lin Xu, Ying-Zheng Zhao Pharmacological Research.2019; 145: 104256. CrossRef - Evaluation of genetic effect of NOS3 and G×E interaction on the variability of serum bilirubin in a Han Chinese population
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Mark McCarty Healthcare.2017; 5(1): 15. CrossRef - Effect of bilirubin concentration on the risk of diabetic complications: A meta-analysis of epidemiologic studies
Bo Zhu, Xiaomei Wu, Yifei Bi, Yang Yang Scientific Reports.2017;[Epub] CrossRef - Role of Bilirubin in Diabetic Vascular Complications: Can Bilirubin Predict More than Just Liver Disease?
Jun Sung Moon Diabetes & Metabolism Journal.2015; 39(5): 384. 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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Abstract
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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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Kaida Mu, Yanping Yang, Xiaofei An, Jie Zhu, Jing Zhang, Yanfei Jiang, Xiaorong Yang, Jinan Zhang Genes & Diseases.2024; 11(5): 101138. CrossRef -
Modulatory role of
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Ghaliah Almalki, Norah Alothman, Gamal Mohamed, Mohammed Akeel, Abd El-Fattah B.M. El-Beltagy, Eman T. Salem Egyptian Journal of Basic and Applied Sciences.2024; 11(1): 536. CrossRef - WITHDRAWN: Research on Traditional Chinese Medicine Syndrome Animal Models and Multi-omics Biomarkers in Type II Diabetes: A Review
Yifei Wang, Yan Gao, Bonian Zhao Pharmacological Research - Modern Chinese Medicine.2024; : 100471. CrossRef - Key biomarkers in type 2 diabetes patients: A systematic review
Thien Ngoc Le, Richard Bright, Vi‐Khanh Truong, Jordan Li, Rajiv Juneja, Krasimir Vasilev Diabetes, Obesity and Metabolism.2024;[Epub] CrossRef - In-depth urinary and exosome proteome profiling analysis identifies novel biomarkers for diabetic kidney disease
Shichun Du, Linhui Zhai, Shu Ye, Le Wang, Muyin Liu, Minjia Tan Science China Life Sciences.2023; 66(11): 2587. CrossRef - Serum Level of Ceruloplasmin, Angiotensin-Converting Enzyme and Transferrin as Markers of Severity in SARS-CoV-2 Infection in Patients with Type 2 Diabetes
Patricia-Andrada Reștea, Ștefan Țigan, Laura Grațiela Vicaș, Luminița Fritea, Eleonora Marian, Tunde Jurca, Annamaria Pallag, Iulius Liviu Mureșan, Corina Moisa, Otilia Micle, Mariana Eugenia Mureșan Microbiology Research.2023; 14(4): 1670. CrossRef - The nephropathy of sickle cell trait and sickle cell disease
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Yuejun Wang, Mingming Zhao, Yu Zhang International Journal of General Medicine.2022; Volume 15: 1985. CrossRef - Molecular Functions of Ceruloplasmin in Metabolic Disease Pathology
Zhidong Liu, Miao Wang, Chunbo Zhang, Shigao Zhou, Guang Ji Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 695. CrossRef - A correlative study of copper, ceruloplasmin, iron, total iron binding capacity and total antioxidant capacity in diabetic nephropathy
Ramlingareddy, Shivashankara A Ramachandrayya, Jeena Jacob, Malathi Mala Biomedicine.2022; 42(3): 469. CrossRef - Novel biomarkers for prognosticating diabetic kidney disease progression
Shilna Muttickal Swaminathan, Indu Ramachandra Rao, Srinivas Vinayak Shenoy, Attur Ravindra Prabhu, Pooja Basthi Mohan, Dharshan Rangaswamy, Mohan V Bhojaraja, Shivashankara Kaniyoor Nagri, Shankar Prasad Nagaraju International Urology and Nephrology.2022; 55(4): 913. CrossRef - Evaluation of Serum Ceruloplasmin Levels as a Biomarker for Oxidative Stress in Patients With Diabetic Retinopathy
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Liliane de Paula Silva, Fabiane Gomes de Moraes Rego, Geraldo Picheth, Marcelo Müller-Santos, Dayane Alberton Journal of Diabetes & Metabolic Disorders.2021; 20(1): 611. CrossRef - Risk assessment for foot ulcers among Tunisian subjects with diabetes: a cross sectional outpatient study
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Natalia Stepanova, Lesya Korol, Olena Burdeyna Indian Journal of Nephrology.2019; 29(5): 309. CrossRef - Recent advancements in biopolymer and metal nanoparticle-based materials in diabetic wound healing management
Veena Vijayakumar, Sushanta K. Samal, Smita Mohanty, Sanjay K. Nayak International Journal of Biological Macromolecules.2019; 122: 137. CrossRef - Rat Böbrek Dokusunda Kurşunun Neden Olduğu Oksidatif Strese Karşı Kitosanın Koruyucu etkisi
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Wan-Ju Kung, Ching-Tang Shih, Chien-Hung Lee, Ching-Chiang Lin Biological Trace Element Research.2018; 185(1): 30. CrossRef - Long-term expression of glomerular genes in diabetic nephropathy
Dominik Chittka, Bernhard Banas, Laura Lennartz, Franz Josef Putz, Kathrin Eidenschink, Sebastian Beck, Thomas Stempfl, Christoph Moehle, Simone Reichelt-Wurm, Miriam C Banas Nephrology Dialysis Transplantation.2018;[Epub] CrossRef - Incidence of chronic kidney disease among people with diabetes: a systematic review of observational studies
D. N. Koye, J. E. Shaw, C. M. Reid, R. C. Atkins, A. T. Reutens, D. J. Magliano Diabetic Medicine.2017; 34(7): 887. CrossRef - Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis
Pengzi Zhang, Jing Lu, Yali Jing, Sunyinyan Tang, Dalong Zhu, Yan Bi Annals of Medicine.2017; 49(2): 106. CrossRef - Biomarkers of diabetic nephropathy: A 2017 update
Nektaria Papadopoulou-Marketou, Christina Kanaka-Gantenbein, Nikolaos Marketos, George P. Chrousos, Ioannis Papassotiriou Critical Reviews in Clinical Laboratory Sciences.2017; 54(5): 326. CrossRef - Serum Vascular Adhesion Protein-1 Predicts End-Stage Renal Disease in Patients with Type 2 Diabetes
Hung-Yuan Li, Hung-An Lin, Feng-Jung Nien, Vin-Cent Wu, Yi-Der Jiang, Tien-Jyun Chang, Hsien-Li Kao, Mao-Shin Lin, Jung-Nan Wei, Cheng-Hsin Lin, Shyang-Rong Shih, Chi-Sheng Hung, Lee-Ming Chuang, Emmanuel A Burdmann PLOS ONE.2016; 11(2): e0147981. CrossRef
- Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea
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Chang-Yun Woo, Ji Yun Jeong, Jung Eun Jang, Jaechan Leem, Chang Hee Jung, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Jung Bok Lee, Ki-Up Lee
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Diabetes Metab J. 2015;39(2):126-131. Published online March 9, 2015
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DOI: https://doi.org/10.4093/dmj.2015.39.2.126
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- Background
Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare. MethodsTo evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital. ResultsAmong the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis. ConclusionThe results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.
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- A Novel Therapeutic Agent for Type 2 Diabetes Mellitus: SGLT2 Inhibitor
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Chang Hee Jung, Jung Eun Jang, Joong-Yeol Park
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Diabetes Metab J. 2014;38(4):261-273. Published online August 20, 2014
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DOI: https://doi.org/10.4093/dmj.2014.38.4.261
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Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder, and a major public health problem that is rapidly increasing in prevalence. Although a wide range of pharmacotherapies for glycemic control is now available, management of T2DM remains complex and challenging. The kidneys contribute immensely to glucose homeostasis by reabsorbing glucose from the glomerular filtrate. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic agents that inhibit glucose absorption from the kidney independent of insulin, offer a unique opportunity to improve the outcomes of patients with T2DM. In this review, we provide an overview of two globally-approved SGLT2 inhibitors, dapagliflozin and canagliflozin, and discuss their effects and safety. This information will help clinicians to decide whether these drugs will benefit their patients.
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