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Volume 44(1); February 2020
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Special Editorial
Editor’s Commentary
Diabetes and Metabolism Journal in 2020: Good to Great
In-Kyung Jeong
Diabetes Metab J. 2020;44(1):1-2.   Published online February 21, 2020
DOI: https://doi.org/10.4093/dmj.2020.0032
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  • 86 Download
  • 1 Web of Science
  • 1 Crossref
PDFPubReader   

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  • How was the Diabetes Metabolism Journal added to MEDLINE?
    Hye Jin Yoo
    Science Editing.2020; 7(2): 201.     CrossRef
Reviews
Guideline/Fact Sheet
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Metformin Treatment for Patients with Diabetes and Chronic Kidney Disease: A Korean Diabetes Association and Korean Society of Nephrology Consensus Statement
Kyu Yeon Hur, Mee Kyoung Kim, Seung Hyun Ko, Miyeun Han, Dong Won Lee, Hyuk-Sang Kwon
Diabetes Metab J. 2020;44(1):3-10.   Published online February 21, 2020
DOI: https://doi.org/10.4093/dmj.2020.0004
  • 10,088 View
  • 362 Download
  • 14 Web of Science
  • 13 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   

The safety of metformin use for patients with type 2 diabetes mellitus (T2DM) and advanced kidney disease is controversial, and more recent guidelines have suggested that metformin be used cautiously in this group until more definitive evidence concerning its safety is available. The Korean Diabetes Association and the Korean Society of Nephrology have agreed on consensus statements concerning metformin use for patients with T2DM and renal dysfunction, particularly when these patients undergo imaging studies using iodinated contrast media (ICM). Metformin can be used safely when the estimated glomerular filtration rate (eGFR) is ≥45 mL/min/1.73 m2. If the eGFR is between 30 and 44 mL/min/1.73 m2, metformin treatment should not be started. If metformin is already in use, a daily dose of ≤1,000 mg is recommended. Metformin is contraindicated when the eGFR is <30 mL/min/1.73 m2. Renal function should be evaluated prior to any ICM-related procedures. During procedures involving intravenous administration of ICM, metformin should be discontinued starting the day of the procedures and up to 48 hours post-procedures if the eGFR is <60 mL/min/1.73 m2.

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Drug/Regimen
Use of SGLT-2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Abdominal Obesity: An Asian Perspective and Expert Recommendations
Wayne Huey-Herng Sheu, Siew Pheng Chan, Bien J. Matawaran, Chaicharn Deerochanawong, Ambrish Mithal, Juliana Chan, Ketut Suastika, Chin Meng Khoo, Huu Man Nguyen, Ji Linong, Andrea Luk, Kun-Ho Yoon
Diabetes Metab J. 2020;44(1):11-32.   Published online February 21, 2020
DOI: https://doi.org/10.4093/dmj.2019.0208
  • 9,507 View
  • 210 Download
  • 33 Web of Science
  • 30 Crossref
AbstractAbstract PDFPubReader   

The prevalence of obesity in Asia is of epidemic proportions, with an estimated 1 billion overweight/obese individuals in the region. The majority of patients with type 2 diabetes mellitus (T2DM) are overweight/obese, which increases the risk of cardiorenal outcomes in these patients; hence, sustained reductions in body weight and visceral adiposity are important management goals. However, most of the glucose-lowering therapies such as insulin, sulfonylureas, glinides, and thiazolidinediones induce weight gain, which makes the management of overweight/obese T2DM patients challenging. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the only oral glucose-lowering agents that have been shown to reduce body weight and visceral adiposity. In addition, SGLT-2 inhibitors therapy reduces ectopic fat deposition and improves adipose tissue function and weight-related quality of life. In this article, we aim to consolidate the existing literature on the effects of SGLT-2 inhibitors in Asian patients with T2DM and to produce clinical recommendations on their use in overweight or obese patients with T2DM. Recommendations from international and regional guidelines, as well as published data from clinical trials in Asian populations and cardiovascular outcomes trials are reviewed. Based on the available data, SGLT-2 inhibitors represent an evidence-based therapeutic option for the management of overweight/obese patients with T2DM.

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Basic Research
Mitochondrial Mechanisms in Diabetic Cardiomyopathy
Johannes Gollmer, Andreas Zirlik, Heiko Bugger
Diabetes Metab J. 2020;44(1):33-53.   Published online February 21, 2020
DOI: https://doi.org/10.4093/dmj.2019.0185
  • 10,807 View
  • 226 Download
  • 61 Web of Science
  • 65 Crossref
AbstractAbstract PDFPubReader   

Mitochondrial medicine is increasingly discussed as a promising therapeutic approach, given that mitochondrial defects are thought to contribute to many prevalent diseases and their complications. In individuals with diabetes mellitus (DM), defects in mitochondrial structure and function occur in many organs throughout the body, contributing both to the pathogenesis of DM and complications of DM. Diabetic cardiomyopathy (DbCM) is increasingly recognized as an underlying cause of increased heart failure in DM, and several mitochondrial mechanisms have been proposed to contribute to the development of DbCM. Well established mechanisms include myocardial energy depletion due to impaired adenosine triphosphate (ATP) synthesis and mitochondrial uncoupling, and increased mitochondrial oxidative stress. A variety of upstream mechanisms of impaired ATP regeneration and increased mitochondrial reactive oxygen species have been proposed, and recent studies now also suggest alterations in mitochondrial dynamics and autophagy, impaired mitochondrial Ca2+ uptake, decreased cardiac adiponectin action, increased O-GlcNAcylation, and impaired activity of sirtuins to contribute to mitochondrial defects in DbCM, among others. In the current review, we present and discuss the evidence that underlies both established and recently proposed mechanisms that are thought to contribute to mitochondrial dysfunction in DbCM.

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Editorial
Technology/Device
The Potential Role of MicroRNA in Diabetic Cardiomyopathy
Jin Hwa Kim
Diabetes Metab J. 2020;44(1):54-55.   Published online February 21, 2020
DOI: https://doi.org/10.4093/dmj.2020.0019
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PDFPubReader   

Citations

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  • What is the impact of ferroptosis on diabetic cardiomyopathy: a systematic review
    Xiaokun Lou, Yuanyuan Zhang, Junfeng Guo, Lina Gao, Yingying Ding, Xinyu Zhuo, Qingqing Lei, Jing Bian, Rumei Lei, Wenyan Gong, Xingwei Zhang, Qibin Jiao
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Original Articles
Drug/Regimen
An Electronic Health Record-Integrated Computerized Intravenous Insulin Infusion Protocol: Clinical Outcomes and in Silico Adjustment
Sung Woon Park, Seunghyun Lee, Won Chul Cha, Kyu Yeon Hur, Jae Hyeon Kim, Moon-Kyu Lee, Sung-Min Park, Sang-Man Jin
Diabetes Metab J. 2020;44(1):56-66.   Published online October 21, 2019
DOI: https://doi.org/10.4093/dmj.2018.0227
  • 6,906 View
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  • 2 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We aimed to describe the outcome of a computerized intravenous insulin infusion (CII) protocol integrated to the electronic health record (EHR) system and to improve the CII protocol in silico using the EHR-based predictors of the outcome.

Methods

Clinical outcomes of the patients who underwent the CII protocol between July 2016 and February 2017 and their matched controls were evaluated. In the CII protocol group (n=91), multivariable binary logistic regression analysis models were used to determine the independent associates with a delayed response (taking ≥6.0 hours for entering a glucose range of 70 to 180 mg/dL). The CII protocol was adjusted in silico according to the EHR-based parameters obtained in the first 3 hours of CII.

Results

Use of the CII protocol was associated with fewer subjects with hypoglycemia alert values (P=0.003), earlier (P=0.002), and more stable (P=0.017) achievement of a glucose range of 70 to 180 mg/dL. Initial glucose level (P=0.001), change in glucose during the first 2 hours (P=0.026), and change in insulin infusion rate during the first 3 hours (P=0.029) were independently associated with delayed responses. Increasing the insulin infusion rate temporarily according to these parameters in silico significantly reduced delayed responses (P<0.0001) without hypoglycemia, especially in refractory patients.

Conclusion

Our CII protocol enabled faster and more stable glycemic control than conventional care with minimized risk of hypoglycemia. An EHR-based adjustment was simulated to reduce delayed responses without increased incidence of hypoglycemia.

Citations

Citations to this article as recorded by  
  • Response: An Electronic Health Record-Integrated Computerized Intravenous Insulin Infusion Protocol: Clinical Outcomes and in Silico Adjustment (Diabetes Metab J 2020;44:56–66)
    Sung Woon Park, Seunghyun Lee, Won Chul Cha, Kyu Yeon Hur, Jae Hyeon Kim, Moon-Kyu Lee, Sung-Min Park, Sang-Man Jin
    Diabetes & Metabolism Journal.2020; 44(2): 358.     CrossRef
  • Letter: An Electronic Health Record-Integrated Computerized Intravenous Insulin Infusion Protocol: Clinical Outcomes and in Silico Adjustment (Diabetes Metab J 2020;44:56–66)
    Dongwon Yi
    Diabetes & Metabolism Journal.2020; 44(2): 354.     CrossRef
Drug/Regimen
Efficacy and Safety of Pioglitazone versus Glimepiride after Metformin and Alogliptin Combination Therapy: A Randomized, Open-Label, Multicenter, Parallel-Controlled Study
Jeong Mi Kim, Sang Soo Kim, Jong Ho Kim, Mi Kyung Kim, Tae Nyun Kim, Soon Hee Lee, Chang Won Lee, Ja Young Park, Eun Sook Kim, Kwang Jae Lee, Young Sik Choi, Duk Kyu Kim, In Joo Kim
Diabetes Metab J. 2020;44(1):67-77.   Published online July 11, 2019
DOI: https://doi.org/10.4093/dmj.2018.0274
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AbstractAbstract PDFPubReader   
Background

There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM.

Methods

This multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investigator's judgement.

Results

Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: −0.81%, P<0.001; glimepiride: −1.05%, P<0.001). However, the pioglitazone-treated group exhibited significantly higher high density lipoprotein cholesterol levels (P<0.001) and significantly lower homeostatic model assessment of insulin resistance values (P<0.001). Relative to pioglitazone, adding glimepiride to metformin plus alogliptin markedly increased the risk of hypoglycemia (pioglitazone: 1/69 cases [1.45%], glimepiride: 14/66 cases [21.21%]; P<0.001).

Conclusion

Among patients with T2DM inadequately controlled using metformin plus alogliptin, the addition of pioglitazone provided comparable glycemic control and various benefits (improvements in lipid profiles, insulin resistance, and hypoglycemia risk) relative to the addition of glimepiride.

Citations

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  • Cost-effectiveness and budget impact analysis of fixed combination of alogliptin and pioglitazone in the treatment of type 2 diabetes mellitus
    Yu.V. Strunina, N.A. Petunina
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  • Pioglitazone-Enhanced Brown Fat Whitening Contributes to Weight Gain in Diet-Induced Obese Mice
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    Joaquim Barreto, Beatriz Luchiari, Vaneza L. W. Wolf, Isabella Bonilha, Ticiane G. Bovi, Barbara S. Assato, Ikaro Breder, Sheila T. Kimura-Medorima, Daniel B. Munhoz, Thiago Quinaglia, Otavio R. Coelho-Filho, Luiz Sergio F. Carvalho, Wilson Nadruz, Andrei
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  • Effects of Glimepiride Combined with Recombinant Human Insulin Injection on Serum IGF-1, VEGF and TRACP-5b Oxidative Stress Levels in Patients with Type 2 Diabetes Mellitus
    Xue Chen, Sheng Kang, Zeqing Bao, Ciara Hughes
    Evidence-Based Complementary and Alternative Medicine.2022; 2022: 1.     CrossRef
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    Kusuma Kumari G., Praveen Thaggikuppe Krishnamurthy, Ravi Kiran Ammu V. V. V., Kurawattimath Vishwanath, S. T. Narenderan, B. Babu, Nagappan Krishnaveni
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  • Compliance with Cardiovascular Prevention Guidelines in Individuals with Type 2 Diabetes in a Middle-Income Region: Cross-Sectional Analysis
    Joaquim Barreto, Beatriz Luchiari, Vaneza Lira W. Wolf, Isabella Bonilha, Ticiane G. Bovi, Barbara S. Assato, Ikaro Breder, Sheila T. Kimura-Medorima, Daniel B. Munhoz, Thiago Quinaglia, Otavio R. Coelho-Filho, Luiz Sérgio Fernandes de Carvalho, Wilson Na
    SSRN Electronic Journal .2021;[Epub]     CrossRef
Drug/Regimen
Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Ji Eun Jun, In-Kyung Jeong, Jae Myung Yu, Sung Rae Kim, In Kye Lee, Kyung-Ah Han, Sung Hee Choi, Soo-Kyung Kim, Hyeong Kyu Park, Ji-Oh Mok, Yong-ho Lee, Hyuk-Sang Kwon, So Hun Kim, Ho-Cheol Kang, Sang Ah Lee, Chang Beom Lee, Kyung Mook Choi, Sung-Ho Her, Won Yong Shin, Mi-Seung Shin, Hyo-Suk Ahn, Seung Ho Kang, Jin-Man Cho, Sang-Ho Jo, Tae-Joon Cha, Seok Yeon Kim, Kyung Heon Won, Dong-Bin Kim, Jae Hyuk Lee, Moon-Kyu Lee
Diabetes Metab J. 2020;44(1):78-90.   Published online June 20, 2019
DOI: https://doi.org/10.4093/dmj.2018.0265
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia.

Methods

This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment.

Results

After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups.

Conclusion

The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

Citations

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Lifesytle
Changes in the Quality of Life in Patients with Type 2 Diabetes Mellitus According to Physician and Patient Behaviors
Young-Joo Kim, In-Kyung Jeong, Sin-Gon Kim, Dong Hyeok Cho, Chong-Hwa Kim, Chul-Sik Kim, Won-Young Lee, Kyu-Chang Won, Jin-Hye Cha, Juneyoung Lee, Doo-Man Kim
Diabetes Metab J. 2020;44(1):91-102.   Published online October 23, 2019
DOI: https://doi.org/10.4093/dmj.2018.0251
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  • 6 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Diabetes mellitus (DM) is the most common chronic metabolic disorder with an increasing prevalence worldwide. According to a previous study, physicians' treatment patterns or patients' behaviors change when they become aware of the risk for cardiovascular (CV) disease in patients with DM. However, there exist controversial reports from previous studies in the impact of physicians' behaviors on the patients' quality of life (QoL) improvements. So we investigate the changes in QoL according to physicians and patients' behavioral changes after the awareness of CV risks in patients with type 2 DM.

Methods

Data were obtained from a prospective, observational study where 799 patients aged ≥40 years with type 2 DM were recruited at 24 tertiary hospitals in Korea. Changes in physicians' behaviors were defined as changes in the dose/type of antihypertensive, lipid-lowering, and anti-platelet therapies within 6-month after the awareness of CV risks in patients. Changes in patients' behaviors were based on lifestyle modifications. Audit of Diabetes Dependent Quality of Life comprising 19-life-domains was used.

Results

The weighted impact score change for local or long-distance journey (P=0.0049), holidays (P=0.0364), and physical health (P=0.0451) domains significantly differed between the two groups; patients whose physician's behaviors changed showed greater improvement than those whose physician's behaviors did not change.

Conclusion

This study demonstrates that changes in physicians' behaviors, as a result of perceiving CV risks, improve QoL in some domains of life in DM patients. Physicians should recognize the importance of understanding CV risks and implement appropriate management.

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Lifesytle
Combined Aerobic and Resistance Exercise Training Reduces Circulating Apolipoprotein J Levels and Improves Insulin Resistance in Postmenopausal Diabetic Women
Yun Kyung Jeon, Sang Soo Kim, Jong Ho Kim, Hyun Jeong Kim, Hyun Jun Kim, Jang Jun Park, Yuen Suk Cho, So Hee Joung, Ji Ryang Kim, Bo Hyun Kim, Sang Heon Song, In Joo Kim, Yong Ki Kim, Young-Bum Kim
Diabetes Metab J. 2020;44(1):103-112.   Published online February 21, 2020
DOI: https://doi.org/10.4093/dmj.2018.0160
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus.

Methods

Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed.

Results

In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt.

Conclusion

Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.

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Clinical Complications
Incidence and Risk Factors for Dementia in Type 2 Diabetes Mellitus: A Nationwide Population-Based Study in Korea
Ji Hee Yu, Kyungdo Han, Sanghyun Park, Hanna Cho, Da Young Lee, Jin-Wook Kim, Ji A Seo, Sin Gon Kim, Sei Hyun Baik, Yong Gyu Park, Kyung Mook Choi, Seon Mee Kim, Nan Hee Kim
Diabetes Metab J. 2020;44(1):113-124.   Published online November 12, 2019
DOI: https://doi.org/10.4093/dmj.2018.0216
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Diabetes mellitus is associated with an increased risk of dementia. We aimed to comprehensively analyze the incidence and risk factors for dementia and young-onset dementia (YOD) in diabetic patients in Korea using the National Health Insurance Service data.

Methods

Between January 1, 2009 and December 31, 2012, a total of 1,917,702 participants with diabetes were included and followed until the date of dementia diagnosis or until December 31, 2015. We evaluated the incidence and risk factors for all dementia, Alzheimer's disease (AD), and vascular dementia (VaD) by Cox proportional hazards analyses. We also compared the impact of risk factors on the occurrence of YOD and late-onset dementia (LOD).

Results

During an average of 5.1 years of follow-up, the incidence of all types of dementia, AD, or VaD was 9.5, 6.8, and 1.3/1,000 person-years, respectively, in participants with diabetes. YOD comprised 4.8% of all dementia occurrence, and the ratio of AD/VaD was 2.1 for YOD compared with 5.5 for LOD. Current smokers and subjects with lower income, plasma glucose levels, body mass index (BMI), and subjects with hypertension, dyslipidemia, vascular complications, depression, and insulin treatment developed dementia more frequently. Vascular risk factors such as smoking, hypertension, and previous cardiovascular diseases were more strongly associated with the development of VaD than AD. Low BMI and a history of stroke or depression had a stronger influence on the development of YOD than LOD.

Conclusion

The optimal management of modifiable risk factors may be important for preventing dementia in subjects with diabetes mellitus.

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Clinical Complications
Hypoglycemia and Dementia Risk in Older Patients with Type 2 Diabetes Mellitus: A Propensity-Score Matched Analysis of a Population-Based Cohort Study
Young-Gun Kim, Dong Gyu Park, So Young Moon, Ja Young Jeon, Hae Jin Kim, Dae Jung Kim, Kwan-Woo Lee, Seung Jin Han
Diabetes Metab J. 2020;44(1):125-133.   Published online October 23, 2019
DOI: https://doi.org/10.4093/dmj.2018.0260
  • 6,909 View
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AbstractAbstract PDFPubReader   
Background

Type 2 diabetes mellitus (T2DM) is associated with an increased risk for dementia. The effects of hypoglycemia on dementia are controversial. Thus, we evaluated whether hypoglycemia increases the risk for dementia in senior patients with T2DM.

Methods

We used the Korean National Health Insurance Service Senior cohort, which includes >10% of the entire senior population of South Korea. In total, 5,966 patients who had ever experienced at least one episode of hypoglycemia were matched with those who had not, using propensity score matching. The risk of dementia was assessed through a survival analysis of matched pairs.

Results

Patients with underlying hypoglycemic events had an increased risk for all-cause dementia, Alzheimer's dementia (AD), and vascular dementia (VaD) compared with those who had not experienced a hypoglycemic event (hazard ratio [HR], 1.254; 95% confidence interval [CI], 1.166 to 1.349; P<0.001 for all-cause dementia; HR, 1.264; 95% CI, 1.162 to 1.375; P<0.001 for AD; HR, 1.286; 95% CI, 1.110 to 1.490; P<0.001 for VaD). According to number of hypoglycemic episodes, the HRs of dementia were 1.170, 1.201, and 1.358 in patients with one hypoglycemic episode, two or three episodes, and more than three episodes, respectively. In the subgroup analysis, hypoglycemia was associated with an increased risk for dementia in both sexes with or without T2DM microvascular or macrovascular complications.

Conclusion

Our findings suggest that patients with a history of hypoglycemia have a higher risk for dementia. This trend was similar for AD and VaD, the two most important subtypes of dementia.

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    Olga V. Saik, Vadim V. Klimontov
    International Journal of Molecular Sciences.2021; 22(22): 12419.     CrossRef
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    Bo Kyung Koo, Seoil Moon, Min Kyong Moon
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    Seung Jin Han
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Metabolic Risk/Epidemiology
Plasma CD36 and Incident Diabetes: A Case-Cohort Study in Danish Men and Women
Yeli Wang, Jingwen Zhu, Sarah Aroner, Kim Overvad, Tianxi Cai, Ming Yang, Anne Tjønneland, Aase Handberg, Majken K. Jensen
Diabetes Metab J. 2020;44(1):134-142.   Published online October 18, 2019
DOI: https://doi.org/10.4093/dmj.2018.0273
  • 4,577 View
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  • 2 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Membrane CD36 is a fatty acid transporter implicated in the pathogenesis of metabolic disease. We aimed to evaluate the association between plasma CD36 levels and diabetes risk and to examine if the association was independent of adiposity among Danish population.

Methods

We conducted a case-cohort study nested within the Danish Diet, Cancer and Health study among participants free of cardiovascular disease, diabetes and cancer and with blood samples and anthropometric measurements (height, weight, waist circumference, and body fat percentage) at baseline (1993 to 1997). CD36 levels were measured in 647 incident diabetes cases that occurred before December 2011 and a total of 3,515 case-cohort participants (236 cases overlap).

Results

Higher plasma CD36 levels were associated with higher diabetes risk after adjusting for age, sex and other lifestyle factors. The hazard ratio (HR) comparing high versus low tertile of plasma CD36 levels was 1.36 (95% confidence interval [CI], 1.00 to 1.86). However, the association lost its significance after further adjustment for different adiposity indices such as body mass index (HR, 1.23; 95% CI, 0.87 to 1.73), waist circumference (HR, 1.21; 95% CI, 0.88 to 1.68) or body fat percentage (HR, 1.20; 95% CI, 0.86 to 1.66). Moreover, raised plasma CD36 levels were moderately associated with diabetes risk among lean participants, but the association was not present among overweight/obese individuals.

Conclusion

Higher plasma CD36 levels were associated with higher diabetes risk, but the association was not independent of adiposity. In this Danish population, the association of CD36 with diabetes risk could be either mediated or confounded by adiposity.

Citations

Citations to this article as recorded by  
  • The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications—Update in Pathogenesis, Treatment and Monitoring
    Kamila Puchałowicz, Monika Ewa Rać
    Cells.2020; 9(8): 1877.     CrossRef
  • The Role of CD36 in Type 2 Diabetes Mellitus: β-Cell Dysfunction and Beyond
    Jun Sung Moon, Udayakumar Karunakaran, Elumalai Suma, Seung Min Chung, Kyu Chang Won
    Diabetes & Metabolism Journal.2020; 44(2): 222.     CrossRef
Metabolic Risk/Epidemiology
Association of Soybean Food Intake and Cardiometabolic Syndrome in Korean Women: Korea National Health and Nutrition Examination Survey (2007 to 2011)
Sook-Hyun Jun, Woo-Kyoung Shin, Yookyung Kim
Diabetes Metab J. 2020;44(1):143-157.   Published online December 2, 2019
DOI: https://doi.org/10.4093/dmj.2019.0078
  • 6,132 View
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  • 6 Web of Science
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AbstractAbstract PDFPubReader   
Background

Soybean food consumption has been considered as a possible way to lower incidence of cardiometabolic syndrome (CMS) among Asians. However, results from studies investigating its efficacy on CMS in Asians have been inconsistent.

Methods

We analyzed the association between soybean intake frequency and prevalence of CMS based on data from the Korea National Health and Nutrition Examination Survey 2007 to 2011. Data of 9,287 women aged 20 to 64 years were analyzed. Food frequency questionnaire was used to assess soybean food consumption frequency. General linear model and multivariable logistic regression model were used to examine the association of soybean intake quintile with CMS and its risk factors. Least square means of metabolic factors mostly showed no significant relevance except liver indexes.

Results

Compared to participants in the 1st quintile (<2 times/week of soybean food), odds ratios (OR) for CMS and abdominal obesity (AO) in the 4th quintile (8.5 times/week<soybean food≤17 times/week) were 0.73 (95% confidence interval [CI], 0.57 to 0.95) and 0.72 (95% CI, 0.58 to 0.90), respectively. After excluding Tofu products, ORs of CMS, AO, high blood pressure, and hypertriglyceridemia were lower than those without excluding Tofu products. However, results still did not show significant inverse linear trend across frequency quintiles.

Conclusion

Our findings suggest that soybean intake of 8.5 to 17 times/week was inversely associated with CMS in Korean women. The relation between soybean intake >17 times/week and CMS varied depending on soybean food items.

Citations

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Basic Research
Fibroblast Growth Factor 21 Attenuates Diabetes-Induced Renal Fibrosis by Negatively Regulating TGF-β-p53-Smad2/3-Mediated Epithelial-to-Mesenchymal Transition via Activation of AKT
Sundong Lin, Lechu Yu, Yongqing Ni, Lulu He, Xiaolu Weng, Xuemian Lu, Chi Zhang
Diabetes Metab J. 2020;44(1):158-172.   Published online October 28, 2019
DOI: https://doi.org/10.4093/dmj.2018.0235
  • 6,135 View
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  • 38 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Epithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study.

Methods

Type 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-α (p53 inhibitor) or 10-[4′-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months.

Results

DN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-β)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-α inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2).

Conclusion

FGF21 prevents renal fibrosis via negative regulation of the TGF-β/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway.

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