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Volume 39(6); December 2015
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Reviews
Complications
Autophagy: A Novel Therapeutic Target for Diabetic Nephropathy
Shinji Kume, Daisuke Koya
Diabetes Metab J. 2015;39(6):451-460.   Published online December 11, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.451
  • 4,998 View
  • 55 Download
  • 80 Web of Science
  • 73 Crossref
AbstractAbstract PDFPubReader   

Diabetic nephropathy is a leading cause of end stage renal disease and its occurance is increasing worldwide. The most effective treatment strategy for the condition is intensive treatment to strictly control glycemia and blood pressure using renin-angiotensin system inhibitors. However, a fraction of patients still go on to reach end stage renal disease even under such intensive care. New therapeutic targets for diabetic nephropathy are, therefore, urgently needed. Autophagy is a major catabolic pathway by which mammalian cells degrade macromolecules and organelles to maintain intracellular homeostasis. The accumulation of damaged proteins and organelles is associated with the pathogenesis of diabetic nephropathy. Autophagy in the kidney is activated under some stress conditions, such as oxidative stress and hypoxia in proximal tubular cells, and occurs even under normal conditions in podocytes. These and other accumulating findings have led to a hypothesis that autophagy is involved in the pathogenesis of diabetic nephropathy. Here, we review recent findings underpinning this hypothesis and discuss the advantages of targeting autophagy for the treatment of diabetic nephropathy.

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Pathophysiology
Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy
Heung Yong Jin, Hong Sun Baek, Tae Sun Park
Diabetes Metab J. 2015;39(6):461-467.   Published online December 11, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.461
  • 3,660 View
  • 41 Download
  • 10 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   

Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN). Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed.

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Genetics
Maturity-Onset Diabetes of the Young: What Do Clinicians Need to Know?
Sung-Hoon Kim
Diabetes Metab J. 2015;39(6):468-477.   Published online December 11, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.468
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Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that is characterized by an early onset, autosomal dominant mode of inheritance and a primary defect in pancreatic β-cell function. MODY represents less than 2% of all diabetes cases and is commonly misdiagnosed as type 1 or type 2 diabetes mellitus. At least 13 MODY subtypes with distinct genetic etiologies have been identified to date. A correct genetic diagnosis is important as it often leads to personalized treatment for those with diabetes and enables predictive genetic testing for their asymptomatic relatives. Next-generation sequencing may provide an efficient method for screening mutations in this form of diabetes as well as identifying new MODY genes. In this review, I discuss a current update on MODY in the literatures and cover the studies that have been performed in Korea.

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Editorial
Complications
Severe Hypoglycemia and Cardiovascular Disease in Type 2 Diabetes
Hyeong Kyu Park
Diabetes Metab J. 2015;39(6):478-480.   Published online December 11, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.478
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Original Articles
Clinical Care/Education
Insulin Initiation in Insulin-Naïve Korean Type 2 Diabetic Patients Inadequately Controlled on Oral Antidiabetic Drugs in Real-World Practice: The Modality of Insulin Treatment Evaluation Study
Sang Soo Kim, In Joo Kim, Yong Ki Kim, Kun Ho Yoon, Ho Young Son, Sung Woo Park, Yeon Ah Sung, Hong Sun Baek
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DOI: https://doi.org/10.4093/dmj.2015.39.6.481
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AbstractAbstract PDFPubReader   
Background

The Modality of Insulin Treatment Evaluation (MOTIV) study was performed to provide real-world data concerning insulin initiation in Korean type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with oral hypoglycemic agents (OHAs).

Methods

This multicenter, non-interventional, prospective, observational study enrolled T2DM patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0%) who had been on OHAs for ≥3 months and were already decided to introduce basal insulin by their physician prior to the start of the study. All treatment decisions were at the physician's discretion to reflect real-world practice.

Results

A total of 9,196 patients were enrolled, and 8,636 patients were included in the analysis (mean duration of diabetes, 8.9 years; mean HbA1c, 9.2%). Basal insulin plus one OHA was the most frequently (51.0%) used regimen. After 6 months of basal insulin treatment, HbA1c decreased to 7.4% and 44.5% of patients reached HbA1c <7%. Body weight increased from 65.2 kg to 65.5 kg, which was not significant. Meanwhile, there was significant increase in the mean daily insulin dose from 16.9 IU at baseline to 24.5 IU at month 6 (P<0.001). Overall, 17.6% of patients experienced at least one hypoglycemic event.

Conclusion

In a real-world setting, the initiation of basal insulin is an effective and well-tolerated treatment option in Korean patients with T2DM who are failing to meet targets with OHA therapy.

Citations

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    Eun-Gyoung Hong, Kyung-Wan Min, Jung Soo Lim, Kyu-Jeung Ahn, Chul Woo Ahn, Jae-Myung Yu, Hye Soon Kim, Hyun Jin Kim, Won Kim, Dong Han Kim, Hak Chul Jang
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    Minyuan Chen, Puhong Zhang, Yang Zhao, Nadila Duolikun, Linong Ji
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 3375.     CrossRef
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    Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
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  • Comparison of Antidiabetic Regimens in Patients with Type 2 Diabetes Uncontrolled by Combination Therapy of Sulfonylurea and Metformin: Results of the MOHAS Disease Registry in Korea
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  • Instauration d’une insulinothérapie chez le patient diabétique de type 2 en médecine générale : Comparaison de l’étude belge InsuStar avec quelques études françaises et internationales
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Clinical Care/Education
Clinical Characteristics and Metabolic Predictors of Rapid Responders to Dipeptidyl Peptidase-4 Inhibitor as an Add-on Therapy to Sulfonylurea and Metformin
Ye An Kim, Won Sang Yoo, Eun Shil Hong, Eu Jeong Ku, Kyeong Seon Park, Soo Lim, Young Min Cho, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi
Diabetes Metab J. 2015;39(6):489-497.   Published online November 27, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.489
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AbstractAbstract PDFPubReader   
Background

Dipeptidyl peptidase-4 (DPP-4) inhibitor add-on therapy is a new option for patients with inadequately controlled type 2 diabetes who are taking combined metformin and sulfonylurea (SU). We evaluated the efficacy and safety of this triple therapy and the characteristics of rapid responders and hypoglycemia-prone patients.

Methods

We included 807 patients with type 2 diabetes who were prescribed a newly added DPP-4 inhibitor to ongoing metformin and SU in 2009 to 2011. Glycemia and other metabolic parameters at baseline, 12, 24, and 52 weeks, as well as episodes of hypoglycemia were analyzed. Rapid responders were defined as patients with ≥25% reduction in glycosylated hemoglobin (HbA1c) within 12 weeks.

Results

At baseline, while on the submaximal metformin and SU combination, the mean HbA1c level was 8.4%. Twelve weeks after initiation of DPP-4 inhibitor add-on, 269 patients (34.4%) achieved an HbA1c level ≤7%. Sixty-six patients (8.2%, 47 men) were rapid responders. The duration of diabetes was shorter in rapid responders, and their baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and homeostasis model assessment of insulin resistance were significantly higher. Patients who experienced hypoglycemia after taking DPP-4 inhibitor add-on were more likely to be female, to have a lower body weight and lower triglyceride and FPG levels, and to have higher homeostasis model assessment of β-cells.

Conclusion

An oral hypoglycemic triple agent combination including a DPP-4 inhibitor was effective in patients with uncontrolled diabetes. Proactive dose reduction of SU should be considered when a DPP-4 inhibitor is added for rapid responders and hypoglycemia-prone patients.

Citations

Citations to this article as recorded by  
  • A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes
    Eugene Han, Hye Sun Park, Obin Kwon, Eun Yeong Choe, Hye Jin Wang, Yong-ho Lee, Sang-Hak Lee, Chul Hoon Kim, Lee-Kyung Kim, Soo Heon Kwak, Kyong Soo Park, Chul Sik Kim, Eun Seok Kang
    Medicine.2016; 95(44): e5155.     CrossRef
Complications
Cardiovascular Disease Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes
Jae-Seung Yun, Seung-Hyun Ko, Sun-Hye Ko, Ki-Ho Song, Ki-Dong Yoo, Kun-Ho Yoon, Yong-Moon Park, Yu-Bae Ahn
Diabetes Metab J. 2015;39(6):498-506.   Published online July 8, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.498
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AbstractAbstract PDFPubReader   
Background

To investigate whether a history of prior cardiovascular disease (CVD) is associated with severe hypoglycemia (SH) in patients with type 2 diabetes.

Methods

We conducted a prospective cohort study from January 2001 to December 2012 with a median follow-up time of 9.5 years (5,814 person-years). Patients aged 25 to 75 years with type 2 diabetes and without chronic kidney disease were enrolled (n=894), and 624 patients completed follow-up. SH was defined as hypoglycemic episodes requiring hospitalization or medical care in an emergency department. We used the Cox proportional hazards regression analysis to test associations between SH episodes and potential explanatory variables.

Results

Among the 624 participants who completed follow-up, 60 patients (9.6%) had previous CVD. Compared to patients without CVD, patients with previous CVD were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline. During follow-up, 62 patients (9.9%) experienced at least one SH episode (incidence of 1.33 per 100 patient-years). The development of SH was associated with a history of CVD (hazard ratio, 1.99; 95% confidence interval, 1.07 to 3.72; P=0.031) after adjusting for sex, age, diabetic duration, hypertension, hemoglobin A1c levels, diabetic complications, cardiovascular autonomic neuropathy, and insulin use.

Conclusion

A history of CVD was an independent risk factor for the development of SH in patients with type 2 diabetes mellitus. For patients with CVD, modulation of glycemic targets and diabetic education for the prevention of hypoglycemia should be implemented.

Citations

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    Ninoschka C. D’Souza, Julian A. Aiken, Emily G. Hoffman, Sara C. Atherley, Sabrina Champsi, Nadia Aleali, Dorsa Shakeri, Maya El-Zahed, Nicky Akbarian, Mehran Nejad-Mansouri, Parinaz Z. Bavani, Richard L. Liggins, Owen Chan, Michael C. Riddell
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • Concomitant Use of Sulfonylureas and β-Blockers and the Risk of Severe Hypoglycemia Among Patients With Type 2 Diabetes: A Population-Based Cohort Study
    Jenny Dimakos, Ying Cui, Robert W. Platt, Christel Renoux, Kristian B. Filion, Antonios Douros
    Diabetes Care.2023; 46(2): 377.     CrossRef
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    Yangyang Zhang, Liang Zhang, Pengcheng Ge, Ruyi Xu, Zhen Ye
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  • Diabetic Neuropathy and Risk of Cardiovascular Disease
    Jae-Seung Yun
    The Journal of Korean Diabetes.2022; 23(4): 245.     CrossRef
  • Randomised controlled trial of pharmacist-led patient counselling in controlling hypoglycaemic attacks in older adults with type 2 diabetes mellitus (ROSE-ADAM): A study protocol of the SUGAR intervention
    Huda Y. Almomani, Carlos Rodriguez Pascual, Sayer I. Al-Azzam, Keivan Ahmadi
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    W. David Strain, Su Down, Pam Brown, Amar Puttanna, Alan Sinclair
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    Jeffrey Freeman
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    Young-ung Kim, Yong-joon Shin, Young Woo Cho
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    Sridharan Raghavan, Wenhui G. Liu, P. Michael Ho, Mary E. Plomondon, Anna E. Barón, Liron Caplan, Karen E. Joynt Maddox, David Magid, David R. Saxon, Corrine I. Voils, Steven M. Bradley, Thomas M. Maddox
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    Eun-Gyo Jeong, Sung Shim Cho, Sang-Hoon Lee, Kang-Min Lee, Seo-Kyung Woo, Yoongoo Kang, Jae-Seung Yun, Seon-Ah Cha, Yoon-Jung Kim, Yu-Bae Ahn, Seung-Hyun Ko, Jung-Min Lee
    The Korean Journal of Internal Medicine.2018; 33(5): 952.     CrossRef
  • Time- and frequency-domain measures of heart rate variability predict cardiovascular outcome in patients with type 2 diabetes
    Seon-Ah Cha, Yong-Moon Park, Jae-Seung Yun, Seung-Hwan Lee, Yu-Bae Ahn, Sung-Rae Kim, Seung-Hyun Ko
    Diabetes Research and Clinical Practice.2018; 143: 159.     CrossRef
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    Alexandra K. Lee, Clare J. Lee, Elbert S. Huang, A. Richey Sharrett, Josef Coresh, Elizabeth Selvin
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    Jin A. Choi, Hyo Won Kim, Jin-Woo Kwon, Yun-sub Shim, Dong Hyun Jee, Jae-Seung Yun, Yu-Bae Ahn, Chan Kee Park, Seung-Hyun Ko, Patrice E. Fort
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    Jae-Seung Yun, Seon-Ah Cha, Tae-Seok Lim, Eun-Young Lee, Ki-Ho Song, Yu-Bae Ahn, Ki-Dong Yoo, Joon-Sung Kim, Yong-Moon Park, Seung-Hyun Ko
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    Seon-Ah Cha, Jae-Seung Yun, Tae-Seok Lim, Kyoungil Min, Ki-Ho Song, Ki-Dong Yoo, Yong-Moon Park, Yu-Bae Ahn, Seung-Hyun Ko, James M Wright
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    Katharina Mattishent, Yoon Kong Loke
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  • Letter: Cardiovascular Disease Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes (Diabetes Metab J 2015;39:498-506)
    Mi-Kyung Kim
    Diabetes & Metabolism Journal.2016; 40(1): 83.     CrossRef
  • Response: Cardiovascular Disease Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes (Diabetes Metab J 2015;39:498-506)
    Jae-Seung Yun, Yu-Bae Ahn
    Diabetes & Metabolism Journal.2016; 40(1): 85.     CrossRef
  • Lipoprotein(a) predicts a new onset of chronic kidney disease in people with Type 2 diabetes mellitus
    J.‐S. Yun, Y.‐B. Ahn, K.‐H. Song, K.‐D. Yoo, Y.‐M. Park, H.‐W. Kim, S.‐H. Ko
    Diabetic Medicine.2016; 33(5): 639.     CrossRef
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    Hyeong Kyu Park
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Obesity and Metabolic Syndrome
The Usefulness of the Glycosylated Hemoglobin Level for the Diagnosis of Gestational Diabetes Mellitus in the Korean Population
Ah Jeong Ryu, Hyuk Jin Moon, Joo Ok Na, Yeo Joo Kim, Sang Jin Kim, Sang Il Mo, Jeong Ran Byun
Diabetes Metab J. 2015;39(6):507-511.   Published online November 23, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.507
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AbstractAbstract PDFPubReader   
Background

An oral glucose tolerance test (OGTT) is the current method used for screening and diagnosis of gestational diabetes mellitus (GDM). OGTT is a relatively complicated procedure and is expensive. Thus, new strategies that do not require fasting or more than a single blood draw may improve the diagnosis of GDM and increase the rate of GDM testing. We investigated the utility of monitoring glycosylated hemoglobin (HbA1c) levels for the diagnosis of GDM.

Methods

The data from 992 pregnant women with estimated gestational ages ranging from 24 to 28 weeks were retrospectively reviewed. There were 367 women with plasma glucose levels ≥140 mg/dL 1 hour after a 50-g OGTT. GDM was diagnosed according to the Carpenter-Coustan criteria for a 3-hour 100 g OGTT. A HbA1c assessment was performed at the same time.

Results

We enrolled 343 women in this study, and there were 109 women with GDM. The area under the curve the receiver operating characteristic curve for HbA1c detection of GDM was 0.852 (95% confidence interval, 0.808 to 0.897). A HbA1c cutoff value ≥5.35% had maximal points on the Youden index (0.581). The sensitivity was 87.2% and the specificity was 70.9% for diagnosing GDM. A threshold value ≥5.35% indicated that 163 patients had GDM and that 68 (41.7%) were false positive. The positive predictive value was 58.3% at this threshold value.

Conclusion

Despite substantial progress in methodology, HbA1c values cannot replace OGTT for the diagnosis of GDM.

Citations

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  • Predelivery HbA1c levels and their relationship with adverse perinatal outcomes in women with normal 75-g OGTT
    Xiaoxia Tang, Jin Wei, Zifeng Jiang, Shaohua Wu
    Archives of Gynecology and Obstetrics.2023;[Epub]     CrossRef
  • The diagnostic value of glycosylated hemoglobin for gestational diabetes mellitus in Asian populations: A systematic review and meta‐analysis
    Jiani Zhang, Fan Zhou, Tingting Xu, Jinfeng Xu, Yaqian Li, Li Lin, Qi Cao, Xiaodong Wang
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  • Glycaemic Variability and Risk Factors of Pregnant Women with and without Gestational Diabetes Mellitus Measured by Continuous Glucose Monitoring
    Martina Gáborová, Viera Doničová, Ivana Bačová, Mária Pallayová, Martin Bona, Igor Peregrim, Soňa Grešová, Judita Štimmelová, Barbora Dzugasová, Lenka Šalamonová Blichová, Viliam Donič
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  • A Review on Research Progress in the Application of Glycosylated Hemoglobin and Glycated Albumin in the Screening and Monitoring of Gestational Diabetes
    Xinyan Liu, Na Wu, Abdulrahman Al-Mureish
    International Journal of General Medicine.2021; Volume 14: 1155.     CrossRef
  • Evaluation of the Combination of HbA1C with Hematocrit for Early Screening of Gestational Diabetes Mellitus
    Ali Reza Norouzi, Mahsa Siavashi, Fatemeh Norouzi, Maryam Talayeh, Somayyeh Noei Teymoordash
    Journal of Obstetrics, Gynecology and Cancer Research.2021; 6(4): 217.     CrossRef
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    Chiamaka Esther Amaefule, Archana Sasitharan, Princee Kalra, Stamatina Iliodromoti, Mohammed S.B. Huda, Ewelina Rogozinska, Javier Zamora, Shakila Thangaratinam
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    Devanshi Dubey, Shipra Kunwar, Uma Gupta
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    Kui Wu, Yan Cheng, Tingting Li, Ziwen Ma, Junxiu Liu, Qingying Zhang, Haidong Cheng
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    Seyoung Kwon, Youngak Na
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Genetics
Non-Association between rs7903146 and rs12255372 Polymorphisms in Transcription Factor 7-Like 2 Gene and Type 2 Diabetes Mellitus in Jahrom City, Iran
Mohammad Pourahmadi, Saiedeh Erfanian, Malihe Moradzadeh, Abdolreza Sotoodeh Jahromi
Diabetes Metab J. 2015;39(6):512-517.   Published online November 13, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.512
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AbstractAbstract PDFPubReader   
Background

Transcription factor 7-like 2 (TCF7L2) is a transcription factor in the Wnt signaling pathway. High levels of TCF7L2 have been reported in most human tissues, including the heart, lung, brain, liver, kidney, placenta, adipose tissues, and pancreatic β-cells. The purpose of this study was to assess the association between TCF7L2 polymorphisms (rs12255372 and rs7903146) and type 2 diabetes mellitus in the city of Jahrom, Iran.

Methods

This case-control study was conducted with 200 patients referred to Diabetes Clinics and 200 healthy subjects in Jahrom City. Biochemical characteristics were first determined. TCF7L2 rs1255372 and rs7903146 polymorphisms were then genotyped using the polymerase chain reaction-restriction fragment length polymorphism method.

Results

T-allele frequencies of both single nucleotide polymorphisms (SNPs) were significantly higher in diabetic patients than in normal glucose-tolerant subjects (rs12255372: 20.3% vs. 14.5%; rs7903146: 28.5% vs. 22.25%). The rs12255372 (G/T) polymorphism analysis showed an odds ratio of 0.473 (95% confidence interval [CI], 0.170 to 1.314; P=0.151) for the TT genotype and 0.646 (95% CI, 0.410 to 1.019; P=0.060) for the TG genotype, compared with the GG genotype. The rs7903146 (C/T) polymorphism odds ratios for TT and TC genotypes were 0.564 (95% CI, 0.280 to 1.135; P=0.109) and 0.751 (95% CI, 0.487 to 1.157; P=0.194) compared with the CC genotype, respectively.

Conclusion

The rs12255372 and rs7903146 SNPs of the TCF7L2 gene were not associated with insulin resistance in the evaluated population.

Citations

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Others
Metformin Promotes Apoptosis but Suppresses Autophagy in Glucose-Deprived H4IIE Hepatocellular Carcinoma Cells
Deok-Bae Park
Diabetes Metab J. 2015;39(6):518-527.   Published online December 11, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.518
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AbstractAbstract PDFPubReader   
Background

Metformin, a well-known anti-diabetic drug, has gained interest due to its association with the reduction of the prevalence of cancer in patients with type 2 diabetes and the anti-proliferative effect of metformin in several cancer cells. Here, we investigated the anti-proliferative effect of metformin with respect to apoptosis and autophagy in H4IIE hepatocellular carcinoma cells.

Methods

H4IIE rat cells were treated with metformin in glucose-free medium for 24 hours and were then subjected to experiments examining the onset of apoptosis and/or autophagy as well as the related signaling pathways.

Results

When H4IIE cells were incubated in glucose-free media for 24 hours, metformin and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) reduced the viability of cells. Inhibition of AMP-activated protein kinase (AMPK) by compound C significantly blocked cell death induced by metformin or AICAR. Pro-apoptotic events (nuclear condensation, hydrolysis of intact poly ADP ribose polymerase and caspase-3) were stimulated by metformin and then suppressed by compound C. Interestingly, the formation of acidic intracellular vesicles, a marker of autophagy, was stimulated by compound C. Although the deprivation of amino acids in culture media also induced apoptosis, neither metformin nor compound C affected cell viability. The expression levels of all of the autophagy-related proteins examined decreased with metformin, and two proteins (light chain 3 and beclin-1) were sensitive to compound C. Among the tested inhibitors against MAP kinases and phosphatidylinositol-3-kinase/mammalian target of rapamycin, SB202190 (against p38MAP kinase) significantly interrupted the effects of metformin.

Conclusion

Our data suggest that metformin induces apoptosis, but suppresses autophagy, in hepatocellular carcinoma cells via signaling pathways, including AMPK and p38 mitogen-activated protein kinase.

Citations

Citations to this article as recorded by  
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Letter
Letter: Prevalence of Depression and Glucose Abnormality in an Urbanizing Rural Population of Bangladesh (Diabetes Metab J 2015;39:218-29)
Tomoyuki Kawada
Diabetes Metab J. 2015;39(6):528-529.   Published online December 11, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.528
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Response
Response: Prevalence of Depression and Glucose Abnormality in an Urbanizing Rural Population of Bangladesh (Diabetes Metab J 2015;39:218-29)
Khurshid Natasha, Akhtar Hussain, A. K. Azad Khan, Bishwajit Bhowmik
Diabetes Metab J. 2015;39(6):530-530.   Published online December 11, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.530
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  • 26 Download
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Diabetes Metab J : Diabetes & Metabolism Journal