Diabetes & Metabolism Journal

Volume 41(1); February 2017

Reviews

Complications
My Sweetheart Is Broken: Role of Glucose in Diabetic Cardiomyopathy: Manoja K. Brahma, Mark E. Pepin, Adam R. Wende; Diabetes Metab J. 2017;41(1):1-9. Published online November 15, 2016; DOI: https://doi.org/10.4093/dmj.2017.41.1.1

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Despite overall reductions in heart disease prevalence, the risk of developing heart failure has remained 2-fold greater among people with diabetes. Growing evidence has supported that fluctuations in glucose level and uptake contribute to cardiovascular disease (CVD) by modifying proteins, DNA, and gene expression. In the case of glucose, clinical studies have shown that increased dietary sugars for healthy individuals or poor glycemic control in diabetic patients further increased CVD risk. Furthermore, even after decades of maintaining tight glycemic control, susceptibility to disease progression can persist following a period of poor glycemic control through a process termed "glycemic memory." In response to chronically elevated glucose levels, a number of studies have identified molecular targets of the glucose-mediated protein posttranslational modification by the addition of an O-linked N-acetylglucosamine to impair contractility, calcium sensitivity, and mitochondrial protein function. Additionally, elevated glucose contributes to dysfunction in coupling glycolysis to glucose oxidation, pentose phosphate pathway, and polyol pathway. Therefore, in the "sweetened" environment associated with hyperglycemia, there are a number of pathways contributing to increased susceptibly to "breaking" the heart of diabetics. In this review we will discuss the unique contribution of glucose to heart disease and recent advances in defining mechanisms of action.

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Diabetes and Heart Failure: Multi-Omics Approaches
Akram Tayanloo-Beik, Peyvand Parhizkar Roudsari, Mostafa Rezaei-Tavirani, Mahmood Biglar, Ozra Tabatabaei-Malazy, Babak Arjmand, Bagher Larijani
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Increased Glucose Availability Attenuates Myocardial Ketone Body Utilization
Manoja K. Brahma, Chae‐Myeong Ha, Mark E. Pepin, Sobuj Mia, Zhihuan Sun, John C. Chatham, Kirk M. Habegger, Evan Dale Abel, Andrew J. Paterson, Martin E. Young, Adam R. Wende
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Jan F.C. Glatz, Miranda Nabben, Martin E. Young, P. Christian Schulze, Heinrich Taegtmeyer, Joost J.F.P. Luiken
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The Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1α–Heme Oxygenase 1 Axis, a Powerful Antioxidative Pathway with Potential to Attenuate Diabetic Cardiomyopathy
Maayan Waldman, Michael Arad, Nader G. Abraham, Edith Hochhauser
Antioxidants & Redox Signaling.2020; 32(17): 1273. CrossRef
miR‑155 modulates high glucose‑induced cardiac fibrosis via the Nrf2/HO‑1 signaling pathway
Yu Li, Jing‑Zhu Duan, Qian He, Chong‑Quan Wang
Molecular Medicine Reports.2020;[Epub] CrossRef
Disruption of energy utilization in diabetic cardiomyopathy; a mini review
Shinsuke Nirengi, Carmem Peres Valgas da Silva, Kristin I Stanford
Current Opinion in Pharmacology.2020; 54: 82. CrossRef
Reduced fatty acid uptake aggravates cardiac contractile dysfunction in streptozotocin-induced diabetic cardiomyopathy
Yogi Umbarawan, Ryo Kawakami, Mas Rizky A. A. Syamsunarno, Norimichi Koitabashi, Hideru Obinata, Aiko Yamaguchi, Hirofumi Hanaoka, Takako Hishiki, Noriyo Hayakawa, Hiroaki Sunaga, Hiroki Matsui, Masahiko Kurabayashi, Tatsuya Iso
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Sungmi Park, Hyeon-Ji Kang, Jae-Han Jeon, Min-Ji Kim, In-Kyu Lee
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Nutrient regulation of signaling and transcription
Gerald W. Hart
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Proteomics of the Rat Myocardium during Development of Type 2 Diabetes Mellitus Reveals Progressive Alterations in Major Metabolic Pathways
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Liang‐jun Yan
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Heart rate dynamics during cardio-pulmonary exercise testing are associated with glycemic control in individuals with type 1 diabetes
Othmar Moser, Max L. Eckstein, Olivia McCarthy, Rachel Deere, Stephen C. Bain, Hanne L. Haahr, Eric Zijlstra, Tim Heise, Richard M. Bracken, Petter Bjornstad
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Pathophysiology
Nuclear Receptors Resolve Endoplasmic Reticulum Stress to Improve Hepatic Insulin Resistance: Jae Man Lee; Diabetes Metab J. 2017;41(1):10-19. Published online February 16, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.1.10

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Abstract PDF PubReader

Chronic endoplasmic reticulum (ER) stress culminating in proteotoxicity contributes to the development of insulin resistance and progression to type 2 diabetes mellitus. Pharmacologic interventions targeting several different nuclear receptors have emerged as potential treatments for insulin resistance. The mechanistic basis for these antidiabetic effects has primarily been attributed to multiple metabolic and inflammatory functions. Here we review recent advances in our understanding of the association of ER stress with insulin resistance and the role of nuclear receptors in promoting ER stress resolution and improving insulin resistance in the liver.

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Duality of Nrf2 in iron-overload cardiomyopathy
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Qingluotongbi formula regulates the LXRα-ERS-SREBP-1c pathway in hepatocytes to alleviate the liver injury caused by Tripterygium wilfordii Hook. f.
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Nuclear‐mitochondrial crosstalk: On the role of the nuclear receptor liver receptor homolog‐1 (NR5A2) in the regulation of mitochondrial metabolism, cell survival, and cancer
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Editorial

Clinical Care/Education
Re-Evaluation of Efficacy of Moderate-Intensity Statins in Korean Patients with Type 2 Diabetes Mellitus: Soo Kyoung Kim; Diabetes Metab J. 2017;41(1):20-22. Published online February 16, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.1.20

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Citations

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Low-density lipoprotein cholesterol goal attainment rates in high-risk patients with cardiovascular diseases and diabetes mellitus in Korea: a retrospective cohort study
Ye Seul Yang, Bo Ram Yang, Mi-Sook Kim, Yunji Hwang, Sung Hee Choi
Lipids in Health and Disease.2020;[Epub] CrossRef
Efficacy and safety of alirocumab in Korean patients with hypercholesterolemia and high cardiovascular risk: subanalysis of the ODYSSEY-KT study
Chang-Wook Nam, Dong-Soo Kim, Jianyong Li, Marie T. Baccara-Dinet, Ivy Li, Ji-Hyun Kim, Chong-Jin Kim
The Korean Journal of Internal Medicine.2019; 34(6): 1252. CrossRef

Original Articles

Clinical Care/Education
Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia in Korean Patients with Type 2 Diabetes Mellitus: Sung Hye Kong, Bo Kyung Koo, Min Kyong Moon; Diabetes Metab J. 2017;41(1):23-30. Published online December 16, 2016; DOI: https://doi.org/10.4093/dmj.2017.41.1.23

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Abstract PDF PubReader

Background

There has been evidences of ethnic differences in the low density lipoprotein cholesterol (LDL-C) lowering effect of statin. We aimed to evaluate the efficacy of moderate-intensity statins in the treatment of dyslipidemia among Korean patients with type 2 diabetes mellitus (T2DM).

Methods

We analyzed a retrospective cohort that consisted of Korean patients with T2DM aged 40 to 75 years who had been prescribed any of the moderate-intensity statins (atorvastatin 10 or 20 mg, rosuvastatin 5 or 10 mg, pitavastatin 2 mg, or pravastatin 40 mg). Among them, only patients with baseline lipid profiles before starting statin treatment were selected, and changes in their lipid profiles before and 6 months after statin therapy were analyzed.

Results

Following the first 6 months of therapy, the overall LDL-C reduction was −47.4% (interquartile range, −56.6% to −34.1%). In total, 92.1% of the participants achieved an LDL-C level of <100 mg/dL, 38.3% had a 30% to 50% reduction in their LDL-C levels, and 42.3% had a reduction in their LDL-C levels greater than 50%. The response rates of each drug for achieving a LDL-C level <100 mg/dL were 81.7%, 93.1%, 95.0%, 95.0%, 96.5%, and 91.7% for treatment with atorvastatin doses of 10 or 20 mg, rosuvastatin 5 or 10 mg, pitavastatin 2 mg, and pravastatin 40 mg, respectively.

Conclusion

In conclusion, the use of moderate-intensity statins reduced LDL-C levels less than 100 mg/dL in most of the Korean patients studied with T2DM. The efficacies of those statins were higher than expected in about 42% of Korean patients with T2DM.

Citations

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Effect of combining evolocumab with statin on carotid intraplaque neovascularization in patients with premature coronary artery disease (EPOCH)
Yanyan Han, Ling Ren, Xiang Fei, Jingjing Wang, Tao Chen, Jun Guo, Qi Wang
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Impact of Plasma Exposure of Statins and Their Metabolites With Major Adverse Cardiovascular Events in Chinese Patients With Coronary Artery Disease
Xiao-hong Zhou, Li-yun Cai, Wei-Hua Lai, Xue Bai, Yi-bin Liu, Qian Zhu, Guo-dong He, Ji-Yan Chen, Min Huang, Zhi-ling Zhou, Shi-long Zhong
Frontiers in Pharmacology.2020;[Epub] CrossRef
Efficacy and Safety of High-Dose Atorvastatin in Moderate-to-High Cardiovascular Risk Postmenopausal Korean Women with Dyslipidemia
Jaecheol Moon, Soyeon Yoo, Gwanpyo Koh, Kyung-Wan Min, Hyun Ho Shin
Journal of Lipid and Atherosclerosis.2020; 9(1): 162. CrossRef
Effects of lowest-dose vs. highest-dose pitavastatin on coronary neointimal hyperplasia at 12-month follow-up in type 2 diabetic patients with non-ST elevation acute coronary syndrome: an optical coherence tomography analysis
Jung Wook Lim, Han Saem Jeong, Soon Jun Hong, Hyo Jeong Kim, Young Chan Kim, Bong Gyun Kang, Su Min Jeon, Jae Young Cho, Seung Hoon Lee, Hyung Joon Joo, Jae Hyoung Park, Cheol Woong Yu
Heart and Vessels.2019; 34(1): 62. CrossRef
Effect of Statin Therapy on Outcomes of Patients With Acute Ischemic Stroke and Atrial Fibrillation
Kang‐Ho Choi, Woo‐Keun Seo, Man‐Seok Park, Joon‐Tae Kim, Jong‐Won Chung, Oh Young Bang, Gyeong‐Moon Kim, Tae‐Jin Song, Bum Joon Kim, Sung Hyuk Heo, Jin‐Man Jung, Kyung‐Mi Oh, Chi Kyung Kim, Sungwook Yu, Kwang‐Yeol Park, Jeong‐Min Kim, Jong‐Ho Park, Jay Ch
Journal of the American Heart Association.2019;[Epub] CrossRef
Moderate-intensity versus high-intensity statin therapy in Korean patients with angina undergoing percutaneous coronary intervention with drug-eluting stents: A propensity-score matching analysis
Mahn-Won Park, Gyung-Min Park, Seungbong Han, Yujin Yang, Yong-Giun Kim, Jae-Hyung Roh, Hyun Woo Park, Jon Suh, Young-Rak Cho, Ki-Bum Won, Soe Hee Ann, Shin-Jae Kim, Dae-Won Kim, Sung Ho Her, Sang-Gon Lee, George C.M. Siontis
PLOS ONE.2018; 13(12): e0207889. CrossRef
Letter: Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia in Korean Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2017;41:23-30)
Jae-Han Jeon
Diabetes & Metabolism Journal.2017; 41(2): 150. CrossRef
Response: Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia in Korean Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2017;41:23-30)
Sung Hye Kong, Bo Kyung Koo, Min Kyong Moon
Diabetes & Metabolism Journal.2017; 41(2): 152. CrossRef

Clinical Care/Education
Practical Focus on American Diabetes Association/European Association for the Study of Diabetes Consensus Algorithm in Patients with Type 2 Diabetes Mellitus: Timely Insulin Initiation and Titration (Iran-AFECT): Mohammad Ebrahim Khamseh, Gholamreza Yousefzadeh, Zahra Banazadeh, Sahar Ghareh; Diabetes Metab J. 2017;41(1):31-37. Published online October 25, 2016; DOI: https://doi.org/10.4093/dmj.2017.41.1.31

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Abstract PDF PubReader: Background
The aim of this study was to evaluate the safety and effectiveness of insulin glargine in a large population from a variety of clinical care in Iranian people with type 2 diabetes mellitus (T2DM) and to measure the percentage of patients achieving glycosylated hemoglobin (HbA1c) <7% by the end of 24 weeks of treatment in routine clinical practice.
Methods
This study was a 24 week, observational study of patients with T2DM, for whom the physician had decided to initiate or to switch to insulin glargine. The safety and efficacy of glargine were assessed at baseline and at week 24.
Results
Seven hundred and twenty-five people with T2DM (63% female) including both insulin naïve and prior insulin users were recruited in this study. The mean age of the participants was 54.2±11.2 years, and the mean HbA1c level was 8.88%±0.93% at baseline. By the end of the study, 27% of the entire participants reached to HbA1c target of less than 7% and 52% had HbA1c ≤7.5%. No serious adverse event was reported in this study. Furthermore, overall hypoglycemia did not increase in prior insulin users and the entire cohort. In addition, body weight did not change in participants while lipid profile improved significantly.
Conclusion
Treatment with insulin glargine could improve glycemic control without increasing the risk of hypoglycemic events in people with T2DM. In addition, a significant clinical improvement was observed in lipid profile.

Epidemiology
Application of the 2013 American College of Cardiology/American Heart Association Cholesterol Guideline to the Korean National Health and Nutrition Examination Surveys from 1998 to 2012: Young Shin Song, Tae Jung Oh, Kyoung Min Kim, Jae Hoon Moon, Sung Hee Choi, Hak Chul Jang, Kyong Soo Park, Soo Lim; Diabetes Metab J. 2017;41(1):38-50. Published online December 16, 2016; DOI: https://doi.org/10.4093/dmj.2017.41.1.38

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Abstract PDF Supplementary Material PubReader

Background

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline for the treatment of blood cholesterol recommends statin therapy for individuals at high risk of atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to investigate serial trends in the percentages of Korean adults considered eligible for statin therapy according to the new ACC/AHA cholesterol guideline.

Methods

Data from the Korean National Health and Nutrition Examination Survey (KNHANES) I (1998, n=7,698), II (2001, n=5,654), III (2005, n=5,269), IV (2007 to 2009, n=15,727), and V (2010 to 2012, n=16,304), which used a stratified, multistage, probability sampling design, were used as representative of the entire Korean population.

Results

The percentage of adults eligible for statin therapy according to the ACC/AHA cholesterol guideline increased with time: 17.0%, 19.0%, 20.8%, 20.2%, and 22.0% in KNHANES I, II, III, IV, and V, respectively (P=0.022). The prevalence of ASCVD was 1.4% in KNHANES I and increased to 3.3% in KNHANES V. The percentage of diabetic patients aged 40 to 75 years with a low density lipoprotein cholesterol levels of 70 to 189 mg/dL increased from 4.8% in KNHANES I to 6.1% in KNHANES V. People with an estimated 10-year ASCVD risk ≥7.5% and aged 40 to 75 years accounted for the largest percentage among the four statin benefit groups: 9.1% in KNHANES I and 11.0% in KNHANES V.

Conclusion

Application of the 2013 ACC/AHA guideline has found that the percentage of Korean adults in the statin benefit groups has increased over the past 15 years.

Citations

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Obesity and Metabolic Syndrome
Relationship between Regional Body Fat Distribution and Diabetes Mellitus: 2008 to 2010 Korean National Health and Nutrition Examination Surveys: Soo In Choi, Dawn Chung, Jung Soo Lim, Mi Young Lee, Jang Yel Shin, Choon Hee Chung, Ji Hye Huh; Diabetes Metab J. 2017;41(1):51-59. Published online December 21, 2016; DOI: https://doi.org/10.4093/dmj.2017.41.1.51

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Background

The aim of this study was to investigate the association between regional body fat distribution, especially leg fat mass, and the prevalence of diabetes mellitus (DM) in adult populations.

Methods

A total of 3,181 men and 3,827 postmenopausal women aged 50 years or older were analyzed based on Korea National Health and Nutrition Examination Surveys (2008 to 2010). Body compositions including muscle mass and regional fat mass were measured using dual-energy X-ray absorptiometry.

Results

The odds ratios (ORs) for DM was higher with increasing truncal fat mass and arm fat mass, while it was lower with increasing leg fat mass. In a partial correlation analysis adjusted for age, leg fat mass was negatively associated with glycosylated hemoglobin in both sexes and fasting glucose in women. Leg fat mass was positively correlated with appendicular skeletal muscle mass and homeostasis model assessment of β cell. In addition, after adjusting for confounding factors, the OR for DM decreased gradually with increasing leg fat mass quartiles in both genders. When we subdivided the participants into four groups based on the median values of leg fat mass and leg muscle mass, higher leg fat mass significantly lowered the risk of DM even though they have smaller leg muscle mass in both genders (P<0.001).

Conclusion

The relationship between fat mass and the prevalence of DM is different according to regional body fat distribution. Higher leg fat mass was associated with a lower risk of DM in Korean populations. Maintaining leg fat mass may be important in preventing impaired glucose tolerance.

Citations

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Obesity and Metabolic Syndrome
Serum Calcium and the Risk of Incident Metabolic Syndrome: A 4.3-Year Retrospective Longitudinal Study: Jong Ha Baek, Sang-Man Jin, Ji Cheol Bae, Jae Hwan Jee, Tae Yang Yu, Soo Kyoung Kim, Kyu Yeon Hur, Moon-Kyu Lee, Jae Hyeon Kim; Diabetes Metab J. 2017;41(1):60-68. Published online December 26, 2016; DOI: https://doi.org/10.4093/dmj.2017.41.1.60

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Background

An association between serum calcium level and risk of metabolic syndrome (MetS) has been suggested in cross-sectional studies. This study aimed to evaluate the association between baseline serum calcium level and risk of incident MetS in a longitudinal study.

Methods

We conducted a retrospective longitudinal study of 12,706 participants without MetS who participated in a health screening program, had normal range serum calcium level at baseline (mean age, 51 years), and were followed up for 4.3 years (18,925 person-years). The risk of developing MetS was analyzed according to the baseline serum calcium levels.

Results

A total of 3,448 incident cases (27.1%) of MetS developed during the follow-up period. The hazard ratio (HR) for incident MetS did not increase with increasing tertile of serum calcium level in an age- and sex-matched model (P for trend=0.915). The HRs (95% confidence interval [CI]) for incident MetS comparing the second and the third tertiles to the first tertile of baseline serum calcium level were 0.91 (95% CI, 0.84 to 0.99) and 0.85 (95% CI, 0.78 to 0.92) in a fully adjusted model, respectively (P for trend=0.001). A decreased risk of incident MetS in higher tertiles of serum calcium level was observed in subjects with central obesity and/or a metabolically unhealthy state at baseline.

Conclusion

There was no positive correlation between baseline serum calcium levels and incident risk of MetS in this longitudinal study. There was an association between higher serum calcium levels and decreased incident MetS in individuals with central obesity or two components of MetS at baseline.

Citations

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Others
Exenatide versus Insulin Lispro Added to Basal Insulin in a Subgroup of Korean Patients with Type 2 Diabetes Mellitus: Kun-Ho Yoon, Elise Hardy, Jenny Han; Diabetes Metab J. 2017;41(1):69-74. Published online December 26, 2016; DOI: https://doi.org/10.4093/dmj.2017.41.1.69

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Abstract PDF PubReader

Background

The prevalence of type 2 diabetes mellitus (T2DM) and obesity is increasing in Korea. Clinical studies in patients with T2DM have shown that combining the glucagon-like peptide-1 receptor agonist exenatide twice daily with basal insulin is an effective glucose-lowering strategy. However, these studies were predominantly conducted in non-Asian populations.

Methods

We conducted a subgroup analysis of data from a multinational, 30-week, randomized, open-label trial to compare the effects of exenatide twice daily (n=10) or three times daily mealtime insulin lispro (n=13) among Korean patients with T2DM inadequately controlled (glycosylated hemoglobin [HbA1c] >7.0%) on metformin plus optimized insulin glargine.

Results

Exenatide twice daily and insulin lispro both reduced HbA1c (mean −1.5% and −1.0%, respectively; P<0.01 vs. baseline). Fasting glucose and weight numerically decreased with exenatide twice daily (−0.7 mmol/L and −0.7 kg, respectively) and numerically increased with insulin lispro (0.9 mmol/L and 1.0 kg, respectively). Minor hypoglycemia occurred in four patients receiving exenatide twice daily and three patients receiving insulin lispro. Gastrointestinal adverse events were the most common with exenatide twice daily treatment.

Conclusion

This analysis found treatment with exenatide twice daily improved glycemic control without weight gain in Korean patients with T2DM unable to achieve glycemic control on metformin plus basal insulin.

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