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Volume 42(4); August 2018
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Reviews
Complications
Diagnosing Diabetic Neuropathy: Something Old, Something New
Ioannis N. Petropoulos, Georgios Ponirakis, Adnan Khan, Hamad Almuhannadi, Hoda Gad, Rayaz A. Malik
Diabetes Metab J. 2018;42(4):255-269.   Published online August 21, 2018
DOI: https://doi.org/10.4093/dmj.2018.0056
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  • 69 Web of Science
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AbstractAbstract PDFPubReader   

There are potentially many ways of assessing diabetic peripheral neuropathy (DPN). However, they do not fulfill U.S. Food and Drug Administration (FDA) requirements in relation to their capacity to assess therapeutic benefit in clinical trials of DPN. Over the past several decades symptoms and signs, quantitative sensory and electrodiagnostic testing have been strongly endorsed, but have consistently failed as surrogate end points in clinical trials. Therefore, there is an unmet need for reliable biomarkers to capture the onset and progression and to facilitate drug discovery in DPN. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging modality for in vivo evaluation of sensory C-fibers. An increasing body of evidence from multiple centers worldwide suggests that CCM fulfills the FDA criteria as a surrogate endpoint of DPN.

Citations

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Obesity and Metabolic Syndrome
Role of the Pyruvate Dehydrogenase Complex in Metabolic Remodeling: Differential Pyruvate Dehydrogenase Complex Functions in Metabolism
Sungmi Park, Jae-Han Jeon, Byong-Keol Min, Chae-Myeong Ha, Themis Thoudam, Bo-Yoon Park, In-Kyu Lee
Diabetes Metab J. 2018;42(4):270-281.   Published online August 21, 2018
DOI: https://doi.org/10.4093/dmj.2018.0101
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  • 105 Web of Science
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AbstractAbstract PDFPubReader   

Mitochondrial dysfunction is a hallmark of metabolic diseases such as obesity, type 2 diabetes mellitus, neurodegenerative diseases, and cancers. Dysfunction occurs in part because of altered regulation of the mitochondrial pyruvate dehydrogenase complex (PDC), which acts as a central metabolic node that mediates pyruvate oxidation after glycolysis and fuels the Krebs cycle to meet energy demands. Fine-tuning of PDC activity has been mainly attributed to post-translational modifications of its subunits, including the extensively studied phosphorylation and de-phosphorylation of the E1α subunit of pyruvate dehydrogenase (PDH), modulated by kinases (pyruvate dehydrogenase kinase [PDK] 1-4) and phosphatases (pyruvate dehydrogenase phosphatase [PDP] 1-2), respectively. In addition to phosphorylation, other covalent modifications, including acetylation and succinylation, and changes in metabolite levels via metabolic pathways linked to utilization of glucose, fatty acids, and amino acids, have been identified. In this review, we will summarize the roles of PDC in diverse tissues and how regulation of its activity is affected in various metabolic disorders.

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Editorial
Epidemiology
Can Air Pollution Biologically Hinder Efforts to Lose Body Weight?
Duk-Hee Lee
Diabetes Metab J. 2018;42(4):282-284.   Published online August 21, 2018
DOI: https://doi.org/10.4093/dmj.2018.0139
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Original Articles
Clinical Diabetes and Therapeutics
Cardio-Ankle Vascular Index as a Surrogate Marker of Early Atherosclerotic Cardiovascular Disease in Koreans with Type 2 Diabetes Mellitus
So Young Park, Sang Ook Chin, Sang Youl Rhee, Seungjoon Oh, Jeong-Taek Woo, Sung Woon Kim, Suk Chon
Diabetes Metab J. 2018;42(4):285-295.   Published online July 27, 2018
DOI: https://doi.org/10.4093/dmj.2017.0080
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AbstractAbstract PDFPubReader   
Background

Carotid artery intima medial thickness (IMT), brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI) are commonly used surrogate markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The cardio-ankle vascular index (CAVI) is a complement to the baPWV, which is affected by blood pressure. However, it is unclear which marker is the most sensitive predictor of atherosclerotic cardiovascular disease (ASCVD).

Methods

This was a retrospective non-interventional study that enrolled 219 patients with T2DM. The correlations among IMT, ABI, and CAVI as well as the relationship of these tests to the 10-year ASCVD risk were also analyzed.

Results

Among the 219 patients, 39 (17.8%) had ASCVD. In the non-ASCVD group, CAVI correlated significantly with IMT after adjusting for confounding variables, but ABI was not associated with CAVI or IMT. The analyses after dividing the non-ASCVD group into three subgroups according to the CAVI score (<8, ≥8 and <9, and ≥9) demonstrated the significant increase in the mean IMT, 10-year ASCVD risk and number of metabolic syndrome risk factors, and decrease in the mean ABI in the high-CAVI group. A high CAVI was an independent risk factor in the non-ASCVD group for both a high 10-year ASCVD risk (≥7.5%; odds ratio [OR], 2.42; P<0.001) and atherosclerosis (mean IMT ≥1 mm; OR, 1.53; P=0.007).

Conclusion

In Korean patients with T2DM without ASCVD, CAVI was the most sensitive of several surrogate markers for the detection of subclinical atherosclerosis.

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  • Response: Cardio-Ankle Vascular Index as a Surrogate Marker of Early Atherosclerotic Cardiovascular Disease in Koreans with Type 2 Diabetes Mellitus (Diabetes Metab J 2018;42:285-95)
    So Young Park, Suk Chon
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  • Letter: Cardio-Ankle Vascular Index as a Surrogate Marker of Early Atherosclerotic Cardiovascular Disease in Koreans with Type 2 Diabetes Mellitus (Diabetes Metab J 2018;42:285-95)
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Epidemiology
Insulin Resistance and the Risk of Diabetes and Dysglycemia in Korean General Adult Population
Jong Ha Baek, Hosu Kim, Kyong Young Kim, Jaehoon Jung
Diabetes Metab J. 2018;42(4):296-307.   Published online April 24, 2018
DOI: https://doi.org/10.4093/dmj.2017.0106
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Insulin resistance is a major pathogenic hallmark of impaired glucose metabolism. We assessed the accuracy of insulin resistance and cut-off values using homeostasis model assessment of insulin resistance (HOMA-IR) to classify type 2 diabetes mellitus (T2DM) and dysglycemia according to age and sex.

Methods

In this cross-sectional study, we analyzed 4,291 anti-diabetic drug-naïve adults (≥20 years) from the 6th Korea National Health and Nutrition Examination Survey in 2015. Metabolic syndrome (MetS) was defined by the modified National Cholesterol Education Program III guideline. Diagnosis of dysglycemia and T2DM were based on fasting glucose and glycosylated hemoglobin levels. The receiver operating characteristic curve and optimal cut-off values of HOMA-IR were assessed to identify T2DM/dysglycemia according to sex and were further analyzed by age.

Results

Sex differences were found in the association of MetS and the different MetS components with T2DM/dysglycemia. The overall optimal cut-off value of HOMA-IR for identifying dysglycemia was 1.6 in both sex. The cut-off values for T2DM were 2.87 in men and 2.36 in women. However, there are differences in diagnostic range of HOMA-IR to distinguish T2DM according to sex and age, and the accuracy of HOMA-IR in identifying T2DM gradually decreased with age especially in women.

Conclusion

Insulin resistance is closely associated with the risk for T2DM/dysglycemia. The accuracy of HOMA-IR levels is characterized by sex- and age-specific differences in identifying T2DM. In addition to insulin resistance index, insulin secretory function, and different MetS components should be considered in the detection of early T2DM, especially in elderly.

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Epidemiology
The Changes of Trends in the Diagnosis and Treatment of Diabetic Foot Ulcer over a 10-Year Period: Single Center Study
Choong Hee Kim, Jun Sung Moon, Seung Min Chung, Eun Jung Kong, Chul Hyun Park, Woo Sung Yoon, Tae Gon Kim, Woong Kim, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee
Diabetes Metab J. 2018;42(4):308-319.   Published online April 27, 2018
DOI: https://doi.org/10.4093/dmj.2017.0076
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

This study aims to describe the trends in the severity and treatment modality of patients with diabetic foot ulcer (DFU) at a single tertiary referral center in Korea over the last 10 years and compare the outcomes before and after the introduction of a multidisciplinary diabetic foot team.

Methods

In this retrospective observational study, electronic medical records of patients from years 2002 to 2015 at single tertiary referral center were reviewed. Based on the year of first admission, patients were assigned to a group either before or after the year 2012, the year the diabetes team launched.

Results

Of the 338 patients with DFU, 229 were first admitted until the year 2011 (group A), while 109 were first admitted since the year 2012 (group B). Mean age was higher in group B, and ulcer size was larger than those of group A. Whereas duration of diabetes was longer in group B, glycemic control was improved (mean glycosylated hemoglobin, 9.48% vs. 8.50%). The proportion of minor lower extremity amputation (LEA) was increased, but length of hospital stay was decreased (73.7±79.6 days vs. 39.8±36.9 days). As critical ischemic limb increased, the proportion of major LEA was not decreased.

Conclusion

Improved glycemic control, multidisciplinary strategies with prompt surgical treatment resulted in reduced length of hospital stay, but these measures did not reduce major LEAs. The increase in critical ischemic limb may have played a role in the unexpected outcome, and may suggest the need for increased vascular intervention strategies in DFU treatment.

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Obesity and Metabolic Syndrome
Air Pollution Has a Significant Negative Impact on Intentional Efforts to Lose Weight: A Global Scale Analysis
Morena Ustulin, So Young Park, Sang Ouk Chin, Suk Chon, Jeong-taek Woo, Sang Youl Rhee
Diabetes Metab J. 2018;42(4):320-329.   Published online April 24, 2018
DOI: https://doi.org/10.4093/dmj.2017.0104
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AbstractAbstract PDFPubReader   
Background

Air pollution causes many diseases and deaths. It is important to see how air pollution affects obesity, which is common worldwide. Therefore, we analyzed data from a smartphone application for intentional weight loss, and then we validated them.

Methods

Our analysis was structured in two parts. We analyzed data from a cohort registered to a smartphone application in 10 large cities of the world and matched it with the annual pollution values. We validated these results using daily pollution data in United States and matching them with user information. Body mass index (BMI) variation between final and initial login time was considered as outcome in the first part, and daily BMI in the validation. We analyzed: daily calories intake, daily weight, daily physical activity, geographical coordinates, seasons, age, gender. Weather Underground application programming interface provided daily climatic values. Annual and daily values of particulate matter PM10 and PM2.5 were extracted. In the first part of the analysis, we used 2,608 users and then 995 users located in United States.

Results

Air pollution was highest in Seoul and lowest in Detroit. Users decreased BMI by 2.14 kg/m2 in average (95% confidence interval, −2.26 to −2.04). From a multilevel model, PM10 (β=0.04, P=0.002) and PM2.5 (β=0.08, P<0.001) had a significant negative effect on weight loss when collected per year. The results were confirmed with the validation (βAQI*time=1.5×10–5; P<0.001) by mixed effects model.

Conclusion

This is the first study that shows how air pollution affects intentional weight loss applied on wider area of the world.

Citations

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  • What could be the reasons for not losing weight even after following a weight loss program?
    Jyoti Dabas, S. Shunmukha Priya, Akshay Alawani, Praveen Budhrani
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    Clílton Kraüss de Oliveira Ferreira, Clara Machado Campolim, Olívia Pizetta Zordão, Fernando Moreira Simabuco, Chadi Pellegrini Anaruma, Rodrigo Martins Pereira, Vitor Ferreira Boico, Luiz Guilherme Salvino, Maíra Maftoum Costa, Nathalia Quintero Ruiz, Le
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    Thavin Kumar Mathana Sundram, Eugenie Sin Sing Tan, Hwee San Lim, Farahnaz Amini, Normina Ahmad Bustami, Pui Yee Tan, Navedur Rehman, Yu Bin Ho, Chung Keat Tan
    Nutrients.2022; 14(22): 4858.     CrossRef
  • Efficiency in reducing air pollutants and healthcare expenditure in the Seoul Metropolitan City of South Korea
    Subal C. Kumbhakar, Jiyeon An, Masoomeh Rashidghalam, Almas Heshmati
    Environmental Science and Pollution Research.2021; 28(20): 25442.     CrossRef
  • Seasonal variation and trends in the Internet searches for losing weight: An infodemiological study
    Ying Teng, Shun-Wei Huang, Zhen Li, Qiao-Mei Xie, Man Zhang, Qiu-Yue Lou, Fang Wang, Yan-Feng Zou
    Obesity Research & Clinical Practice.2020; 14(3): 225.     CrossRef
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Obesity and Metabolic Syndrome
Associations between Body Mass Index and Chronic Kidney Disease in Type 2 Diabetes Mellitus Patients: Findings from the Northeast of Thailand
Sojib Bin Zaman, Naznin Hossain, Muntasirur Rahman
Diabetes Metab J. 2018;42(4):330-337.   Published online August 21, 2018
DOI: https://doi.org/10.4093/dmj.2017.0052
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  • 11 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   
Background

Chronic kidney disease (CKD) has emerged as a public health burden globally. Obesity and long-term hyperglycaemia can initiate the renal vascular complications in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of body mass index (BMI) with the CKD in patients with T2DM.

Methods

This study has used retrospective medical records, biochemical reports, and anthropometric measurements of 3,580 T2DM patients which were collected between January to December 2015 from a district hospital in Thailand. CKD was defined according to the measurement of estimated glomerular filtration rate (<60 mL/min/1.73 m2). Multiple logistic regression analysis was used to explore the association between BMI and CKD in patients with T2DM.

Results

The mean age of the participants was 60.86±9.67 years, 53.68% had poor glycaemic control, and 45.21% were overweight. About one-in-four (23.26%) T2DM patients had CKD. The mean BMI of non-CKD group was slightly higher (25.30 kg/m2 vs. 24.30 kg/m2) when compared with CKD patients. Multivariable analysis showed that older age, female sex, hypertension, and microalbuminuria were associated with the presence of CKD. No association was observed between CKD and poorly controlled glycosylated hemoglobin or hypercholesterolemia. Adjusted analysis further showed overweight and obesity were negatively associated with CKD (adjusted odds ratio [AOR], 0.73; 95% confidence interval [CI], 0.58 to 0.93) and (AOR, 0.53; 95% CI, 0.35 to 0.81), respectively.

Conclusion

The negative association of BMI with CKD could reflect the reverse causality. Lower BMI might not lead a diabetic patient to develop CKD, but there are possibilities that CKD leads the patient to experience reduced BMI.

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    Brunilda Elezi, Skender Topi, Erjona Abazaj
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    Bo-Yeon Kim, Dug-Hyun Choi, Chan-Hee Jung, Ji-Oh Mok, Chul-Hee Kim
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Brief Reports
Complications
Effect of Empagliflozin, a Selective Sodium-Glucose Cotransporter 2 Inhibitor, on Kidney and Peripheral Nerves in Streptozotocin-Induced Diabetic Rats
Kyung Ae Lee, Heung Yong Jin, Na Young Lee, Yu Ji Kim, Tae Sun Park
Diabetes Metab J. 2018;42(4):338-342.   Published online April 25, 2018
DOI: https://doi.org/10.4093/dmj.2017.0095
  • 4,155 View
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  • 17 Web of Science
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AbstractAbstract PDFPubReader   

The effect of sodium-glucose cotransporter 2 inhibitors on peripheral nerves and kidneys in diabetes mellitus (DM) remains unexplored. Therefore, this study aimed to explore the effect of empagliflozin in diabetic rats. DM in rats was induced by streptozotocin injection, and diabetic rats were treated with empagliflozin 3 or 10 mg/kg. Following 24-week treatment, response thresholds to four different stimuli were tested and found to be lower in diabetic rats than in normal rats. Empagliflozin significantly prevented hypersensitivity (P<0.05) and the loss of skin intraepidermal nerve fibers, and mesangial matrix expansion in diabetic rats. Results of this study demonstrate the potential therapeutic effects of empagliflozin for the treatment of diabetic peripheral neuropathy and nephropathy.

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Others
Serum Soluble Epidermal Growth Factor Receptor Level Increase in Patients Newly Diagnosed with Type 2 Diabetes Mellitus
Ji Min Kim, Sorim Choung, Kyong Hye Joung, Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku
Diabetes Metab J. 2018;42(4):343-347.   Published online May 2, 2018
DOI: https://doi.org/10.4093/dmj.2017.0082
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AbstractAbstract PDFPubReader   

We analyzed circulating soluble epidermal growth factor receptor (sEGFR) levels in humans. Serum sEGFR levels were higher in subjects with newly diagnosed type 2 diabetes mellitus compared with controls. Serum sEGFR was positively correlated with glycosylated hemoglobin and serum glucose and negatively correlated with serum insulin and C-peptide levels.

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Letter
Letter: Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome (Diabetes Metab J 2018;42:207-14)
Jin Hwa Kim
Diabetes Metab J. 2018;42(4):348-349.   Published online August 21, 2018
DOI: https://doi.org/10.4093/dmj.2018.0135
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  • PCSK9 gene participates in the development of primary dyslipidemias
    D Matías-Pérez, AD Pérez-Santiago, MA Sánchez Medina, JJ Alpuche Osorno, IA García-Montalvo
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Response
Response: Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome (Diabetes Metab J 2018;42:207-14)
Sung Woo Kim, Keun-Gyu Park
Diabetes Metab J. 2018;42(4):350-352.   Published online August 21, 2018
DOI: https://doi.org/10.4093/dmj.2018.0138
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Erratum
Corrigendum
Corrigendum: Figure Correction. Primary Cilia as a Signaling Platform for Control of Energy Metabolism
Min-Seon Kim
Diabetes Metab J. 2018;42(4):354-354.   Published online August 21, 2018
DOI: https://doi.org/10.4093/dmj.2018.0115
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