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Volume 40(5); October 2016
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Reviews
Clinical Care/Education
Gemigliptin: An Update of Its Clinical Use in the Management of Type 2 Diabetes Mellitus
Sung-Ho Kim, Jung-Hwa Yoo, Woo Je Lee, Cheol-Young Park
Diabetes Metab J. 2016;40(5):339-353.   Published online September 12, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.339
  • 6,402 View
  • 163 Download
  • 42 Web of Science
  • 40 Crossref
AbstractAbstract PDFPubReader   

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antidiabetic agent for the treatment of type 2 diabetes mellitus. They increase endogenous levels of incretin hormones, which stimulate glucose-dependent insulin secretion, decrease glucagon secretion, and contribute to reducing postprandial hyperglycemia. Although DPP-4 inhibitors have similar benefits, they can be differentiated in terms of their chemical structure, pharmacology, efficacy and safety profiles, and clinical considerations. Gemigliptin (brand name: Zemiglo), developed by LG Life Sciences, is a potent, selective, competitive, and long acting DPP-4 inhibitor. Various studies have shown that gemigliptin is an optimized DPP-4 inhibitor in terms of efficacy, safety, and patient compliance for treatment of type 2 diabetes mellitus. In this review, we summarize the characteristics of gemigliptin and discuss its potential benefits in clinical practice.

Citations

Citations to this article as recorded by  
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  • Increasing Age Associated with Higher Dipeptidyl Peptidase-4 Inhibition Rate Is a Predictive Factor for Efficacy of Dipeptidyl Peptidase-4 Inhibitors
    Sangmo Hong, Chang Hee Jung, Song Han, Cheol-Young Park
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    Petr Busek, Jonathan S. Duke-Cohan, Aleksi Sedo
    Cancers.2022; 14(9): 2072.     CrossRef
  • Divergent Reaction of Activated Pyridines with α,α-Difluorinated gem-Diols: Regioselective Synthesis of gem-Difluorinated Dihydropyridines and Dihydropyridones
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  • Pharmacokinetic and Pharmacodynamic Comparison of Two Formulations of a Fixed-Dose Combination of Gemigliptin/Rosuvastatin 50/20 mg: A Randomized, Open-Label, Single-Dose, Two-Way Crossover Study
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    Drug Design, Development and Therapy.2021; Volume 15: 651.     CrossRef
  • Efficacy and Safety of the Novel Dipeptidyl Peptidase-4 Inhibitor Gemigliptin in the Management of Type 2 Diabetes: A Meta-Analysis
    Deep Dutta, Anshita Agarwal, Indira Maisnam, Rajiv Singla, Deepak Khandelwal, Meha Sharma
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  • Structure–Activity Relationship Analysis of Cocrystallized Gliptin-like Pyrrolidine, Trifluorophenyl, and Pyrimidine-2,4-Dione Dipeptidyl Peptidase-4 Inhibitors
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  • The vasodilatory effect of gemigliptin via activation of voltage-dependent K+ channels and SERCA pumps in aortic smooth muscle
    Hee Seok Jung, Mi Seon Seo, Jin Ryeol An, Minji Kang, Ryeon Heo, Hongliang Li, Won-Kyo Jung, Il-Whan Choi, Eun-Hee Cho, Hongzoo Park, Young Min Bae, Won Sun Park
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  • Incretin Mimetics as Rational Candidates for the Treatment of Traumatic Brain Injury
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  • Dipeptidyl Peptidase-4 Inhibitors versus Other Antidiabetic Drugs Added to Metformin Monotherapy in Diabetic Retinopathy Progression: A Real World-Based Cohort Study
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  • Comparative efficacy and safety of gemigliptin versus linagliptin in type 2 diabetes patients with renal impairment: A 40‐week extension of the GUARD randomized study
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Complications
The Effect of Bariatric Surgery on Diabetic Retinopathy: Good, Bad, or Both?
Dora M. Gorman, Carel W. le Roux, Neil G. Docherty
Diabetes Metab J. 2016;40(5):354-364.   Published online September 27, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.354
  • 4,336 View
  • 48 Download
  • 22 Web of Science
  • 28 Crossref
AbstractAbstract PDFPubReader   

Bariatric surgery, initially intended as a weight-loss procedure, is superior to standard lifestyle intervention and pharmacological therapy for type 2 diabetes in obese individuals. Intensive medical management of hyperglycemia is associated with improved microvascular outcomes. Whether or not the reduction in hyperglycemia observed after bariatric surgery translates to improved microvascular outcomes is yet to be determined. There is substantial heterogeneity in the data relating to the impact of bariatric surgery on diabetic retinopathy (DR), the most common microvascular complication of diabetes. This review aims to collate the recent data on retinal outcomes after bariatric surgery. This comprehensive evaluation revealed that the majority of DR cases remain stable after surgery. However, risk of progression of pre-existing DR and the development of new DR is not eliminated by surgery. Instances of regression of DR are also noted. Potential risk factors for deterioration include severity of DR at the time of surgery and the magnitude of glycated hemoglobin reduction. Concerns also exist over the detrimental effects of postprandial hypoglycemia after surgery. In vivo studies evaluating the chronology of DR development and the impact of bariatric surgery could provide clarity on the situation. For now, however, the effect of bariatric surgery on DR remains inconclusive.

Citations

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Editorial
Others
Blood Glucose Measurement: Is Serum Equal to Plasma?
Hye Soon Kim
Diabetes Metab J. 2016;40(5):365-366.   Published online October 12, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.365
  • 4,421 View
  • 78 Download
  • 25 Web of Science
  • 27 Crossref
PDFPubReader   

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Original Articles
Epidemiology
Serum 25-Hydroxyvitamin D Concentration Is Independently Inversely Associated with Insulin Resistance in the Healthy, Non-Obese Korean Population
So Young Ock, Kyoung Hwa Ha, Bu Kyung Kim, Hyeon Chang Kim, Jee-Seon Shim, Myung Ha Lee, Young Me Yoon, Dae Jung Kim
Diabetes Metab J. 2016;40(5):367-375.   Published online July 26, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.367
  • 3,735 View
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We evaluated the associations between 25-hydroxyvitamin D (25(OH)D) concentrations in serum and insulin resistance in the healthy Korean population.

Methods

We conducted this cross-sectional analysis in 1,807 healthy Korean people (628 men and 1,179 women) aged 30 to 64 years in the Cardiovascular and Metabolic Disease Etiologic Research Center study. All participants were assessed for 25(OH)D, fasting glucose, and insulin levels, and completed a health examination and lifestyle questionnaire according to standard procedures. Insulin resistance was defined as the homeostasis model assessment insulin resistance higher than the 75 percentile.

Results

Compared to those in the highest tertile (≥14.3 ng/mL), the odds ratio (OR) for insulin resistance was 1.37 (95% confidence interval [CI], 1.01 to 1.86) for the 1st tertile (<9.7 ng/mL) and 1.19 (95% CI, 0.08 to 1.62) for the 2nd tertile (9.7 to 14.3 ng/mL) after adjusting for age, gender, waist circumference, alcohol consumption, smoking status, physical exercise, season, and cohort. After stratification of the subjects by adiposity, these associations remained only in non-obese subjects (lowest tertile vs. highest tertile, multivariable OR, 1.64; 95% CI, 1.05 to 2.56).

Conclusion

Serum 25(OH)D has an independent inverse association with insulin resistance in the healthy, non-obese Korean population, even among people with vitamin D insufficiency.

Citations

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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
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
Diabetes Metab J. 2016;40(5):376-385.   Published online April 5, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.376
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AbstractAbstract PDFPubReader   
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.

Methods

Seven-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.

Results

Statin 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.

Conclusion

Statins 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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Obesity and Metabolic Syndrome
Effects of Body Weight Reduction on Serum Irisin and Metabolic Parameters in Obese Subjects
Yaeko Fukushima, Satoshi Kurose, Hiromi Shinno, Ha Cao Thi Thu, Nana Takao, Hiromi Tsutsumi, Takaaki Hasegawa, Toshiaki Nakajima, Yutaka Kimura
Diabetes Metab J. 2016;40(5):386-395.   Published online September 27, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.386
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AbstractAbstract PDFPubReader   
Background

Irisin is a myokine implicated in lipid and glucose metabolism. The objective of this study is to examine the effect of a body weight reduction on the serum irisin level and physical indicators in obese Japanese patients without diabetes.

Methods

The subjects were 22 patients (male/female, 5/17; age, 46.1±16.0 years; body mass index [BMI], 36.9±5.0 kg/m2) who completed a 6-month body weight reduction program at our clinic. The program included diet, exercise therapy and cognitive behavioral therapy. Blood parameters, body composition, exercise tolerance, homeostasis model assessment of insulin resistance (HOMA-IR), and serum irisin were determined before and after intervention, and relationships among changes in these data were examined.

Results

There were significant decreases in body weight and BMI after the intervention. Irisin before the intervention was significantly positively correlated with HOMA-IR (r=0.434, P<0.05). The mean irisin level showed no significant change after the intervention in all participants. However, improvements in % body fat, subcutaneous fat area, triglycerides, and fasting glucose were significantly greater in patients with an increase in irisin compared to those with a decrease in irisin after the intervention. Patients with an increase in irisin also had significantly lower fasting insulin (9.7±4.8 vs. 16.4±8.2, P<0.05) and HOMA-IR (2.2±1.1 vs. 3.7±1.6, P<0.05) after the intervention, compared to patients with a decrease in irisin.

Conclusion

Body weight reduction did not alter irisin levels. However, irisin may play important roles in fat and glucose metabolism and insulin resistance, and the effects of body weight reduction on irisin kinetics may be a key for obesity treatment.

Citations

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    Hossein Shirvani, Saleh Rahmati-Ahmadabad
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    Syeda Sadia Fatima, Erum Khalid, Asma Akbar Ladak, Syed Adnan Ali
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    Gyuri Kim, Seung‐Eun Lee, You‐Bin Lee, Ji Eun Jun, Jiyeon Ahn, Ji Cheol Bae, Sang‐Man Jin, Kyu Yeon Hur, Jae Hwan Jee, Moon‐Kyu Lee, Jae Hyeon Kim
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    P. Amaro Andrade, B.K. Souza Silveira, A. Corrêa Rodrigues, F.M. Oliveira da Silva, C.O. Barbosa Rosa, R.C. Gonçalves Alfenas
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    Ioannis G. Fatouros
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Others
Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor
Na Han, You Jeong Kim, Su Min Park, Seung Man Kim, Ji Suk Lee, Hye Sook Jung, Eun Ju Lee, Tae Kyoon Kim, Tae Nyun Kim, Min Jeong Kwon, Soon Hee Lee, Mi-kyung Kim, Byoung Doo Rhee, Jeong Hyun Park
Diabetes Metab J. 2016;40(5):396-405.   Published online September 1, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.396
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AbstractAbstract PDFPubReader   
Background

Cognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear. We examined the role of FOXO transcription factors and the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt and apoptosis-related signaling pathways in PC-12 cells exposed to repeated glucose deprivation/reperfusion.

Methods

PC-12 cells were exposed to control (Dulbecco's Modified Eagle Medium [DMEM] containing 25 mM glucose) or glucose deprivation/reperfusion (DMEM with 0 mM glucose for 6 hours and then DMEM with 25 mM glucose for 18 hours) for 5 days. MTT assay and Western blot analysis were performed for cell viability, apoptosis, and the expression of survival signaling pathways. FOXO3/4',6-diamidino-2-phenylindole staining was done to ascertain the involvement of FOXO transcription factors in glucose deprivation/reperfusion conditions.

Results

Compared to PC-12 cells not exposed to hypoglycemia, cells exposed to glucose deprivation/reperfusion showed a reduction of cell viability, decreased expression of phosphorylated Akt and Bcl-2, and an increase of cleaved caspase-3 expression. Of note, FOXO3 protein was localized in the nuclei of glucose deprivation/reperfusion cells but not in the control cells.

Conclusion

Repeated glucose deprivation/reperfusion caused the neuronal cell death. Activated FOXO3 via the PI3K/Akt pathway in repeated glucose deprivation/reperfusion was involved in genes related to apoptosis.

Citations

Citations to this article as recorded by  
  • Predictive factors for the development of diabetes in cancer patients treated with phosphatidylinositol 3-kinase inhibitors
    Gyuri Kim, Myungeun Yoo, Min Hee Hong, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Hye Ryun Kim, Yong-ho Lee, Byoung Chul Cho
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Others
Rg3 Improves Mitochondrial Function and the Expression of Key Genes Involved in Mitochondrial Biogenesis in C2C12 Myotubes
Min Joo Kim, Young Do Koo, Min Kim, Soo Lim, Young Joo Park, Sung Soo Chung, Hak C. Jang, Kyong Soo Park
Diabetes Metab J. 2016;40(5):406-413.   Published online August 12, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.406
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  • 21 Web of Science
  • 22 Crossref
AbstractAbstract PDFPubReader   
Background

Panax ginseng has glucose-lowering effects, some of which are associated with the improvement in insulin resistance in skeletal muscle. Because mitochondria play a pivotal role in the insulin resistance of skeletal muscle, we investigated the effects of the ginsenoside Rg3, one of the active components of P. ginseng, on mitochondrial function and biogenesis in C2C12 myotubes.

Methods

C2C12 myotubes were treated with Rg3 for 24 hours. Insulin signaling pathway proteins were examined by Western blot. Cellular adenosine triphosphate (ATP) levels and the oxygen consumption rate were measured. The protein or mRNA levels of mitochondrial complexes were evaluated by Western blot and quantitative reverse transcription polymerase chain reaction analysis.

Results

Rg3 treatment to C2C12 cells activated the insulin signaling pathway proteins, insulin receptor substrate-1 and Akt. Rg3 increased ATP production and the oxygen consumption rate, suggesting improved mitochondrial function. Rg3 increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α, nuclear respiratory factor 1, and mitochondrial transcription factor, which are transcription factors related to mitochondrial biogenesis. Subsequent increased expression of mitochondrial complex IV and V was also observed.

Conclusion

Our results suggest that Rg3 improves mitochondrial function and the expression of key genes involved in mitochondrial biogenesis, leading to an improvement in insulin resistance in skeletal muscle. Rg3 may have the potential to be developed as an anti-hyperglycemic agent.

Citations

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Brief Report
Others
A Potential Issue with Screening Prediabetes or Diabetes Using Serum Glucose: A Delay in Diagnosis
Jun Goo Kang, Cheol-Young Park, Sung-Hee Ihm, Sung Woo Park
Diabetes Metab J. 2016;40(5):414-417.   Published online September 1, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.414
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AbstractAbstract PDFPubReader   

The aim of this study was to compare the fasting serum glucose level with the fasting plasma glucose level for diagnosing hyperglycemic states in real-life clinical situations. Additionally, we investigated a usual delay in sample processing and how such delays can impact the diagnosis of hyperglycemic states. Among 1,254 participants who had normoglycemia or impaired fasting glucose (IFG) assessed by the fasting serum glucose level, 20.9% were newly diagnosed with diabetes based on the plasma fasting glucose level. Of the participants with normoglycemia, 62.1% and 14.2% were newly diagnosed with IFG and diabetes, respectively, according to the plasma fasting glucose level. In our clinical laboratory for performing health examinations, the time delay from blood sampling to glycemic testing averaged 78±52 minutes. These findings show that the ordinary time delay for sample processing of the serum glucose for screening hyperglycemic states may be an important reason for these diagnoses to be underestimated in Korea.

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Letter
Letter: Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2016;40:297-307)
Dongwon Yi
Diabetes Metab J. 2016;40(5):418-419.   Published online October 12, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.418
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PDFPubReader   
Response
Response: Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2016;40:297-307)
Jun Ouk Ha, Tae Hee Lee, Chang Won Lee
Diabetes Metab J. 2016;40(5):420-421.   Published online October 12, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.420
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Diabetes Metab J : Diabetes & Metabolism Journal