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Volume 37(3); June 2013
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Reviews
Neonatal Diabetes Caused by Activating Mutations in the Sulphonylurea Receptor
Peter Proks
Diabetes Metab J. 2013;37(3):157-164.   Published online June 14, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.3.157
  • 2,905 View
  • 47 Download
  • 10 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM

Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in pancreatic β-cells play a crucial role in insulin secretion and glucose homeostasis. These channels are composed of two subunits: a pore-forming subunit (Kir6.2) and a regulatory subunit (sulphonylurea receptor-1). Recent studies identified large number of gain of function mutations in the regulatory subunit of the channel which cause neonatal diabetes. Majority of mutations cause neonatal diabetes alone, however some lead to a severe form of neonatal diabetes with associated neurological complications. This review focuses on the functional effects of these mutations as well as the implications for treatment.

Citations

Citations to this article as recorded by  
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    Kenju Shimomura, Yuko Maejima
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    Heidi de Wet, Peter Proks
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  • Reclasificación y transferencia de insulina a sulfonilureas en un paciente con mutación en KCNJ11 tras 15 años de tratamiento con insulina
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Chemokine Systems Link Obesity to Insulin Resistance
Tsuguhito Ota
Diabetes Metab J. 2013;37(3):165-172.   Published online June 14, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.3.165
  • 3,944 View
  • 69 Download
  • 79 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM

Obesity is a state of chronic low-grade systemic inflammation. This chronic inflammation is deeply involved in insulin resistance, which is the underlying condition of type 2 diabetes and metabolic syndrome. A significant advance in our understanding of obesity-associated inflammation and insulin resistance has been recognition of the critical role of adipose tissue macrophages (ATMs). Chemokines are small proteins that direct the trafficking of immune cells to sites of inflammation. In addition, chemokines activate the production and secretion of inflammatory cytokines through specific G protein-coupled receptors. ATM accumulation through C-C motif chemokine receptor 2 and its ligand monocyte chemoattractant protein-1 is considered pivotal in the development of insulin resistance. However, chemokine systems appear to exhibit a high degree of functional redundancy. Currently, more than 50 chemokines and 18 chemokine receptors exhibiting various physiological and pathological properties have been discovered. Therefore, additional, unidentified chemokine/chemokine receptor pathways that may play significant roles in ATM recruitment and insulin sensitivity remain to be fully identified. This review focuses on some of the latest findings on chemokine systems linking obesity to inflammation and subsequent development of insulin resistance.

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Editorial
The Effects of Green Tea on Obesity and Type 2 Diabetes
Hyun Min Kim, Jaetaek Kim
Diabetes Metab J. 2013;37(3):173-175.   Published online June 14, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.3.173
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Original Articles
An In Vitro Model to Probe the Regulation of Adipocyte Differentiation under Hyperglycemia
Kusampudi Shilpa, Thangaraj Dinesh, Baddireddi Subhadra Lakshmi
Diabetes Metab J. 2013;37(3):176-180.   Published online June 14, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.3.176
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AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

The aim of this study was an in vitro investigation of the effect of high glucose concentration on adipogenesis, as prolonged hyperglycemia alters adipocyte differentiation.

Methods

3T3-L1 preadipocytes differentiated in the presence of varying concentrations of glucose (25, 45, 65, 85, and 105 mM) were assessed for adipogenesis using AdipoRed (Lonza) assay. Cell viability and proliferation were measured using MTT reduction and [3H] thymidine incorporation assay. The extent of glucose uptake and glycogen synthesis were measured using radiolabelled 2-deoxy-D-[1-3H] glucose and [14C]-UDP-glucose. The gene level expression was evaluated using reverse transcription-polymerase chain reaction and protein expression was studied using Western blot analysis.

Results

Glucose at 105 mM concentration was observed to inhibit adipogenesis through inhibition of CCAAT-enhancer-binding proteins, sterol regulatory element-binding protein, peroxisome proliferator-activated receptor and adiponectin. High concentration of glucose induced stress by increasing levels of toll-like receptor 4, nuclear factor κB and tumor necrosis factor α thereby generating activated preadipocytes. These cells entered the state of hyperplasia through inhibition of p27 and proliferation was found to increase through activation of protein kinase B via phosphoinositide 3 kinase dependent pathway. This condition inhibited insulin signaling through decrease in insulin receptor β. Although the glucose transporter 4 (GLUT4) protein remained unaltered with the glycogen synthesis inhibited, the cells were found to exhibit an increase in glucose uptake via GLUT1.

Conclusion

Adipogenesis in the presence of 105 mM glucose leads to an uncontrolled proliferation of activated preadipocytes providing an insight towards understanding obesity.

Citations

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  • Response: AnIn VitroModel to Probe the Regulation of Adipocyte Differentiation under Hyperglycemia (Diabetes Metab J2013;37:176-80)
    Kusampudi Shilpa, Thangaraj Dinesh, Baddireddi Subhadra Lakshmi
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Safety and Efficacy of Modern Insulin Analogues
Hye Jin Yoo, Keun Yong Park, Kang Seo Park, Kyu Jeung Ahn, Kyung Wan Min, Jeong Hyun Park, Sang Ah Chang, Bong Soo Cha, Dong-Jun Kim, Yong Seong Kim, Tae Keun Oh, Suk Chon, Il Seong Nam-Goong, Mi Jin Kim, Hye-Soon Kim, Young Sik Choi, You Hern Ahn, Sora Lee, Sei Hyun Baik
Diabetes Metab J. 2013;37(3):181-189.   Published online June 14, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.3.181
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  • 9 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

A1chieve® was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart.

Methods

Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints.

Results

Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7±15.9 to 72.5±13.5) while the mean body weight was slightly increased (0.6±3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%±2.2%, 2.5±4.7 mmol/L, and 4.0±6.4 mmol/L, respectively.

Conclusion

The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.

Citations

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Corrected QT Interval Prolongation during Severe Hypoglycemia without Hypokalemia in Patients with Type 2 Diabetes
Jae Won Beom, Jung Min Kim, Eun Joo Chung, Ju Yeong Kim, Seung Yeong Ko, Sang Don Na, Cheol Hwan Kim, Gun Park, Mi Yeon Kang
Diabetes Metab J. 2013;37(3):190-195.   Published online June 14, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.3.190
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  • 11 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

To evaluate the effects of severe hypoglycemia without hypokalemia on the electrocardiogram in patients with type 2 diabetes in real-life conditions.

Methods

Electrocardiograms of adult type 2 diabetic patients during the episodes of severe hypoglycemia and the recovered stage were obtained and analysed between October 1, 2011 and May 31, 2012. Patients who maintained the normal serum sodium and potassium levels during the episodes of severe hypoglycemia were only selected as the subjects of this study. Severe hypoglycemia was defined, in this study, as the condition requiring active medical assistance such as administering carbohydrate when serum glucose level was less than 60 mg/dL.

Results

Nine type 2 diabetes patients (seven men, two women) were included in the study. The mean subject age was 73.2±7.7 years. The mean hemoglobin A1c level was 6.07%±1.19%. The median duration of diabetes was 10 years (range, 3.5 to 30 years). Corrected QT (QTc) intervals were significantly increased during the episodes of severe hypoglycemia compared to the recovered stage (447.6±18.2 ms vs. 417.2±30.6 ms; P<0.05). However, the morphology and the amplitude of the T waves were not changed and ST-segment elevation and/or depression were not found during the episodes of severe hypoglycemia.

Conclusion

In this study, QTc interval prolongation during the episodes of severe hypoglycemia was observed without hypokalemia. Therefore, the distinct alterations in cardiac repolarization during the episodes of severe hypoglycemia may not be associated with hypokalemia.

Citations

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  • Prevalence of QT prolongation and its risk factors in patients with type 2 diabetes
    Khaled Aburisheh, Mohammad F. AlKheraiji, Saleh I. Alwalan, Arthur C. Isnani, Mohamed Rafiullah, Muhammad Mujammami, Assim A. Alfadda
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Effect of Green Tea Extract/Poly-γ-Glutamic Acid Complex in Obese Type 2 Diabetic Mice
Ki-Cheor Bae, Jae-Hyung Park, Ann-Yae Na, Sun-Joo Kim, Shinbyoung Ahn, Sang-Pyo Kim, Byung-Chul Oh, Ho-Chan Cho, Yong Woon Kim, Dae-Kyu Song
Diabetes Metab J. 2013;37(3):196-206.   Published online June 14, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.3.196
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  • 10 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

The increasing prevalence of type 2 diabetes mellitus (T2DM) is associated with the rapid spread of obesity. Obesity induces insulin resistance, resulting in β-cell dysfunction and thus T2DM. Green tea extract (GTE) has been known to prevent obesity and T2DM, but this effect is still being debated. Our previous results suggested that circulating green tea gallated catechins (GCs) hinders postprandial blood glucose lowering, regardless of reducing glucose and cholesterol absorption when GCs are present in the intestinal lumen. This study aimed to compare the effect of GTE with that of GTE coadministered with poly-γ-glutamic acid (γ-PGA), which is likely to inhibit the intestinal absorption of GCs.

Methods

The db/db mice and age-matched nondiabetic mice were provided with normal chow diet containing GTE (1%), γ-PGA (0.1%), or GTE+γ-PGA (1%:0.1%) for 4 weeks.

Results

In nondiabetic mice, none of the drugs showed any effects after 4 weeks. In db/db mice, however, weight gain and body fat gain were significantly reduced in the GTE+γ-PGA group compared to nondrug-treated db/db control mice without the corresponding changes in food intake and appetite. Glucose intolerance was also ameliorated in the GTE+γ-PGA group. Histopathological analyses showed that GTE+γ-PGA-treated db/db mice had a significantly reduced incidence of fatty liver and decreased pancreatic islet size. Neither GTE nor γ-PGA treatment showed any significant results.

Conclusion

These results suggest that GTE+γ-PGA treatment than GTE or γ-PGA alone may be a useful tool for preventing both obesity and obesity-induced T2DM.

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Brief Report
Beneficial Effects of Omega-3 Fatty Acids on Low Density Lipoprotein Particle Size in Patients with Type 2 Diabetes Already under Statin Therapy
Myung Won Lee, Jeong Kyung Park, Jae Won Hong, Kwang Joon Kim, Dong Yeob Shin, Chul Woo Ahn, Young Duk Song, Hong Keun Cho, Seok Won Park, Eun Jig Lee
Diabetes Metab J. 2013;37(3):207-211.   Published online June 14, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.3.207
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Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C), additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (≥200 mg/dL) while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL) particle size and triglyceride (TG) level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%±3.1% vs. 2.3%±3.6%, P=0.024; -41.0%±24.1% vs. -24.2%±31.9%, P=0.049). Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects.

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Letter
Response
Response: Efficacy and Safety of Biphasic Insulin Aspart 30/70 in Type 2 Diabetes Suboptimally Controlled on Oral Antidiabetic Therapy in Korea: A Multicenter, Open-Label, Single-Arm Study (Diabetes Metab J 2013;37:117-24)
Kee-Ho Song, Jung Min Kim, Jung-Hyun Noh, Yongsoo Park, Hyun-Shik Son, Kyong Wan Min, Kyung Soo Ko
Diabetes Metab J. 2013;37(3):214-215.   Published online June 14, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.3.214
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Erratum
Erratum: Incorrect Volume Number
Diabetes Metab J. 2013;37(3):216-216.   Published online June 14, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.3.216
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Diabetes Metab J : Diabetes & Metabolism Journal