Diabetes & Metabolism Journal

Volume 46(3); May 2022

Reviews

Guideline/Fact Sheet
Effect of Carbohydrate-Restricted Diets and Intermittent Fasting on Obesity, Type 2 Diabetes Mellitus, and Hypertension Management: Consensus Statement of the Korean Society for the Study of Obesity, Korean Diabetes Association, and Korean Society of Hypertension: Jong Han Choi, Yoon Jeong Cho, Hyun-Jin Kim, Seung-Hyun Ko, Suk Chon, Jee-Hyun Kang, Kyoung-Kon Kim, Eun Mi Kim, Hyun Jung Kim, Kee-Ho Song, Ga Eun Nam, Kwang Il Kim, Committee of Clinical Practice Guidelines, Korean Society for the Study of Obesity (KSSO), Committee of Clinical Practice Guidelines and Committee of Food and Nutrition, Korean Diabetes Association (KDA), Policy Committee of Korean Society of Hypertension (KSH), Policy Development Committee of National Academy of Medicine of Korea (NAMOK); Diabetes Metab J. 2022;46(3):355-376. Published online May 25, 2022; DOI: https://doi.org/10.4093/dmj.2022.0038

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Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations. A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled trials (RCTs) of carbohydrate-restricted diets and 10 articles on eight RCTs of IF was performed. Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes mellitus, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension. Here, we describe the results of our analysis and the evidence for these recommendations.

Citations

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Alzheimer’s Disease, Obesity, and Type 2 Diabetes: Focus on Common Neuroglial Dysfunctions (Critical Review and New Data on Human Brain and Models)
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Medical nutrition therapy for diabetes mellitus
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Euglycemic diabetic ketoacidosis development in a patient with type 2 diabetes receiving a sodium-glucose cotransporter-2 inhibitor and a carbohydrate-restricted diet
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Comprehensive Understanding for Application in Korean Patients with Type 2 Diabetes Mellitus of the Consensus Statement on Carbohydrate-Restricted Diets by Korean Diabetes Association, Korean Society for the Study of Obesity, and Korean Society of Hyperte
Jong Han Choi, Jee-Hyun Kang, Suk Chon
Diabetes & Metabolism Journal.2022; 46(3): 377. CrossRef
The Related Metabolic Diseases and Treatments of Obesity
Ming Yang, Shuai Liu, Chunye Zhang
Healthcare.2022; 10(9): 1616. CrossRef
Updated Meta-Analysis of Studies from 2011 to 2021 Comparing the Effectiveness of Intermittent Energy Restriction and Continuous Energy Restriction
Kyoung-Kon Kim, Jee-Hyun Kang, Eun Mi Kim
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Guideline/Fact Sheet
Comprehensive Understanding for Application in Korean Patients with Type 2 Diabetes Mellitus of the Consensus Statement on Carbohydrate-Restricted Diets by Korean Diabetes Association, Korean Society for the Study of Obesity, and Korean Society of Hypertension: Jong Han Choi, Jee-Hyun Kang, Suk Chon; Diabetes Metab J. 2022;46(3):377-390. Published online May 25, 2022; DOI: https://doi.org/10.4093/dmj.2022.0051

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The Joint Committee of the Korean Diabetes Association, the Korean Society for the Study of Obesity, and the Korean Society of Hypertension announced a consensus statement on carbohydrate-restricted diets and intermittent fasting, representing an emerging and popular dietary pattern. In this statement, we recommend moderately-low-carbohydrate or low-carbohydrate diets, not a very-low-carbohydrate diet, for patients with type 2 diabetes mellitus. These diets can be considered a dietary regimen to improve glycemic control and reduce body weight in adults with type 2 diabetes mellitus. This review provides the detailed results of a meta-analysis and systematic literature review on the potential harms and benefits of carbohydrate-restricted diets in patients with diabetes. We expect that this review will help experts and patients by fostering an in-depth understanding and appropriate application of carbohydrate-restricted diets in the comprehensive management of diabetes.

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Medical nutrition therapy for diabetes mellitus
Suk Chon
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Metabolic Risk/Epidemiology
Lifestyle Interventions for Non-Obese Patients Both with, and at Risk, of Non-Alcoholic Fatty Liver Disease: Xin-Lei Zhang, Ting-Yao Wang, Giovanni Targher, Christopher D. Byrne, Ming-Hua Zheng; Diabetes Metab J. 2022;46(3):391-401. Published online May 25, 2022; DOI: https://doi.org/10.4093/dmj.2022.0048

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Non-alcoholic fatty liver disease occurring in non-obese subjects (the so-called non-obese NAFLD) is a highly prevalent but neglected liver condition, which is closely associated with metabolic disorders and suboptimal lifestyles. Landmark studies have shown that lifestyle interventions are potentially beneficial in decreasing the risk of developing non-obese NAFLD and in ameliorating NAFLD in non-obese individuals with pre-existing NAFLD. Lifestyle interventions usually refer to changes in eating habits and physical activity, both of which have a powerful effect on non-obese NAFLD and on risk factors for non-obese NAFLD. However, to date, patients and health-care professionals have a poor awareness and understanding of non-obese NAFLD and the beneficial effects of lifestyle interventions in this patient population. The aim of this narrative review is to briefly discuss the evidence for the effects of lifestyle changes and what changes are needed amongst medical personnel and other stakeholders in order to raise awareness of non-obese NAFLD.

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Meta-analysis of randomized controlled trials of the effects of synbiotics, probiotics, or prebiotics in controlling glucose homeostasis in non-alcoholic fatty liver disease patients
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Sulwon Lecture 2021

Basic Research
Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c): Tae Kwan Yoon, Chan Hee Lee, Obin Kwon, Min-Seon Kim; Diabetes Metab J. 2022;46(3):402-413. Published online May 25, 2022; DOI: https://doi.org/10.4093/dmj.2022.0092

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Low levels of mitochondrial stress are beneficial for organismal health and survival through a process known as mitohormesis. Mitohormetic responses occur during or after exercise and may mediate some salutary effects of exercise on metabolism. Exercise-related mitohormesis involves reactive oxygen species production, mitochondrial unfolded protein response (UPR^mt), and release of mitochondria-derived peptides (MDPs). MDPs are a group of small peptides encoded by mitochondrial DNA with beneficial metabolic effects. Among MDPs, mitochondrial ORF of the 12S rRNA type-c (MOTS-c) is the most associated with exercise. MOTS-c expression levels increase in skeletal muscles, systemic circulation, and the hypothalamus upon exercise. Systemic MOTS-c administration increases exercise performance by boosting skeletal muscle stress responses and by enhancing metabolic adaptation to exercise. Exogenous MOTS-c also stimulates thermogenesis in subcutaneous white adipose tissues, thereby enhancing energy expenditure and contributing to the anti-obesity effects of exercise training. This review briefly summarizes the mitohormetic mechanisms of exercise with an emphasis on MOTS-c.

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Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives
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Mitochondria-derived peptide is an effective target for treating streptozotocin induced painful diabetic neuropathy through induction of activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1alpha -mediated mitochondrial b
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Editorial

Implication of Sex Differences in Visceral Fat for the Assessment of Incidence Risk of Type 2 Diabetes Mellitus: Sang Hyeon Ju, Hyon-Seung Yi; Diabetes Metab J. 2022;46(3):414-416. Published online May 25, 2022; DOI: https://doi.org/10.4093/dmj.2022.0089

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Prediction of high visceral adipose tissue for sex‐specific community residents in Taiwan
Yu‐Hsuan Chang, Chin‐Sung Chang, Chieh‐Yu Liu, Yin‐Fan Chang, Shiow‐Ching Shun
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Association of triglyceride glucose index and triglyceride glucose-body mass index with sudden cardiac arrest in the general population
Shuijing Zhang, Wenbing Liu, Bin Xu, Shuguang Wang, Zhongyan Du, Wenke Cheng
Cardiovascular Diabetology.2024;[Epub] CrossRef
Determination of SRPA and adiposity measures and its association with glycemic status in type 2 diabetics having high mean HbA1c in a private clinic of a city in west India
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The predictive significance of lipid accumulation products for future diabetes in a non-diabetic population from a gender perspective: an analysis using time-dependent receiver operating characteristics
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Original Articles

Guideline/Fact Sheet
Diabetes Fact Sheet in Korea 2021: Jae Hyun Bae, Kyung-Do Han, Seung-Hyun Ko, Ye Seul Yang, Jong Han Choi, Kyung Mook Choi, Hyuk-Sang Kwon, Kyu Chang Won, on Behalf of the Committee of Media-Public Relation of the Korean Diabetes Association; Diabetes Metab J. 2022;46(3):417-426. Published online May 25, 2022; DOI: https://doi.org/10.4093/dmj.2022.0106

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Background
This study aimed to investigate the prevalence and management of diabetes mellitus, risk-factor control, and comorbidities among Korean adults.
Methods
We conducted a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey to assess the prevalence, treatment, risk factors, comorbidities, and self-management behaviors of diabetes mellitus from 2019 to 2020. We also analyzed data from the Korean National Health Insurance Service to evaluate the use of antidiabetic medications in people with diabetes mellitus from 2002 through 2018.
Results
Among Korean adults aged 30 years or older, the estimated prevalence of diabetes mellitus was 16.7% in 2020. From 2019 through 2020, 65.8% of adults with diabetes mellitus were aware of the disease and treated with antidiabetic medications. The percentage of adults with diabetes mellitus who achieved glycosylated hemoglobin (HbA1c) <6.5% was 24.5% despite the increased use of new antidiabetic medications. We found that adults with diabetes mellitus who achieved all three goals of HbA1c <6.5%, blood pressure (BP) <140/85 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL were 9.7%. The percentage of self-management behaviors was lower in men than women. Excess energy intake was observed in 16.7% of adults with diabetes mellitus.
Conclusion
The prevalence of diabetes mellitus among Korean adults remained high. Only 9.7% of adults with diabetes mellitus achieved all glycemic, BP, and lipid controls from 2019 to 2020. Continuous evaluation of national diabetes statistics and a national effort to increase awareness of diabetes mellitus and improve comprehensive diabetes care are needed.

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British Journal of Health Psychology.2024;[Epub] CrossRef
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2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association
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당뇨병 치료의 진화: 관해를 향해가는 혁신적 약물치료와 첨단 관리기기의 결합
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Diabetes & Metabolism Journal.2023; 47(2): 211. CrossRef
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COVID-19
Association of Metabolic Syndrome with COVID-19 in the Republic of Korea: Woo-Hwi Jeon, Jeong-Yeon Seon, So-Youn Park, In-Hwan Oh; Diabetes Metab J. 2022;46(3):427-438. Published online November 26, 2021; DOI: https://doi.org/10.4093/dmj.2021.0105

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Background
Metabolic syndrome (MetS) is reportedly a crucial risk factor for coronavirus disease 2019 (COVID-19). Since the epidemiological studies that examine this association are few and include small samples, we investigated the relationship between MetS and COVID-19 severity and death using a larger sample in the Republic of Korea.
Methods
We analyzed 66,321 patients, 4,066 of whom had COVID-19. We used chi-square tests to examine patients’ characteristics. We performed logistic regression analysis to analyze differences in COVID-19 infection and clinical outcomes according to the presence of MetS.
Results
Although MetS was not significantly associated with COVID-19 risk, acquiring MetS was significantly associated with the risk of severe COVID-19 outcomes (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.34 to 2.91; P=0.001). The mortality risk was significantly higher in COVID-19 patients with MetS (OR, 1.74; 95% CI, 1.17 to 2.59; P=0.006). Patients with abnormal waist circumference were approximately 2.07 times more likely to develop severe COVID-19 (P<0.001), and high-density lipoprotein cholesterol (HDL-C) levels were significantly associated with COVID-19; the mortality risk due to COVID-19 was 1.74 times higher in men with an HDL-C level of <40 mg/dL and in women with an HDL-C level of <50 mg/dL (P=0.012).
Conclusion
COVID-19 is likely associated with severity and death in patients with MetS or in patients with MetS risk factors. Therefore, patients with MetS or those with abnormal waist circumference and HDL-C levels need to be treated with caution.

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Heterogeneity in familial clustering of metabolic syndrome components in the multiethnic GENNID study
Jia Y. Wan, Deborah Goodman, Sukh Makhnoon, Trina M. Norden‐Krichmar, Baolin Wu, Karen L. Edwards
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Identification of shared genetic risks underlying metabolic syndrome and its related traits in the Korean population
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Frontiers in Genetics.2024;[Epub] CrossRef
Metabolic health is more strongly associated with the severity and mortality of coronavirus disease 2019 than obesity
Hye Yeon Koo, Jae-Ryun Lee, Jin Yong Lee, Hyejin Lee
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Associated Factors with Changes of Metabolic Abnormalities among General Population in COVID-19 Pandemic
Eunjoo Kwon, Eun-Hee Nah, Suyoung Kim, Seon Cho, Hyeran Park
Korean Journal of Health Promotion.2023; 23(2): 55. CrossRef
Association between metabolic syndrome and mortality in patients with COVID-19: A nationwide cohort study
Hyo Jin Park, Jin-Hyung Jung, Kyungdo Han, Jean Shin, Yoojeong Lee, Yujin Chang, Kyeyeung Park, Yoon Jeong Cho, Youn Seon Choi, Seon Mee Kim, Ga Eun Nam
Obesity Research & Clinical Practice.2022; 16(6): 484. CrossRef

Drug/Regimen
Comparison of Prevailing Insulin Regimens at Different Time Periods in Hospitalized Patients: A Real-World Experience from a Tertiary Hospital: Sun Joon Moon, Hun Jee Choe, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho; Diabetes Metab J. 2022;46(3):439-450. Published online October 20, 2021; DOI: https://doi.org/10.4093/dmj.2021.0065

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Abstract PDF Supplementary Material PubReader ePub: Background
Prevailing insulin regimens for glycemic control in hospitalized patients have changed over time. We aimed to determine whether the current basal-bolus insulin (BBI) regimen is superior to the previous insulin regimen, mainly comprising split-mixed insulin therapy.
Methods
This was a single tertiary center, retrospective observational study that included non-critically ill patients with type 2 diabetes mellitus who were treated with split-mixed insulin regimens from 2004 to 2007 (period 1) and with BBI from 2008 to 2018 (period 2). Patients from each period were analyzed after propensity score matching. The mean difference in glucose levels and the achievement of fasting and preprandial glycemic targets by day 6 of admission were assessed. The total daily insulin dose, incidence of hypoglycemia, and length of hospital stay were also evaluated.
Results
Among 244 patients from each period, both fasting glucose (estimated mean±standard error, 147.4±3.1 mg/dL vs. 129.4±3.2 mg/dL, P<0.001, day 6) and preprandial glucose (177.7±2.8 mg/dL vs. 152.8±2.8 mg/dL, P<0.001, day 6) were lower in period 2 than in period 1. By day 6 of hospital admission, 42.6% and 67.2% of patients achieved a preprandial glycemic target of <140 mg/dL in periods 1 and 2, respectively (relative risk, 2.00; 95% confidence interval, 1.54 to 2.59), without an increased incidence of hypoglycemia. Length of stay was shorter in period 2 (10.23±0.26 days vs. 8.70±0.26 days, P<0.001).
Conclusion
BBI improved glycemic control in a more efficacious manner than a split-mixed insulin regimen without increasing the risk of hypoglycemia in a hospital setting.

Type 1 Diabetes
Identification of Key Genes and Pathways in Peripheral Blood Mononuclear Cells of Type 1 Diabetes Mellitus by Integrated Bioinformatics Analysis: Xing Li, Mingyu Liao, Jiangheng Guan, Ling Zhou, Rufei Shen, Min Long, Jiaqing Shao; Diabetes Metab J. 2022;46(3):451-463. Published online April 1, 2022; DOI: https://doi.org/10.4093/dmj.2021.0018

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Background
The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM.
Methods
Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb).
Results
We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM.
Conclusion
These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications.

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Single-cell and transcriptomic analyses reveal the influence of diabetes on ovarian cancer
Zhihao Zhao, Qilin Wang, Fang Zhao, Junnan Ma, Xue Sui, Hyok Chol Choe, Peng Chen, Xue Gao, Lin Zhang
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Bioinformatics analysis identifies TGF-β signaling pathway-associated molecular subtypes and gene signature in diabetic foot
Guanggang Du, Jie Chen, Xuezhu Zhu, Zongdong Zhu
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Shudeb Babu Sen Omit, Salma Akhter, Humayan Kabir Rana, A. R. M. Mahamudul Hasan Rana, Nitun Kumar Podder, Mahmudul Islam Rakib, Ashadun Nobi, Ali Imran
BioMed Research International.2023;[Epub] CrossRef
Advanced Delivery Strategies for Immunotherapy in Type I Diabetes Mellitus
Mingshu Huang, Weixing Chen, Min Wang, Yisheng Huang, Hongyu Liu, Yue Ming, Yuanxin Chen, Zhengming Tang, Bo Jia
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Identification of the key genes of tuberculosis and construction of a diagnostic model via weighted gene co-expression network analysis
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Probing biological network in concurrent carcinomas and Type-2 diabetes for potential biomarker screening: An advanced computational paradigm
Abdullah Al Marzan, Shatila Shahi, Md Sakil Arman, Md Zafrul Hasan, Ajit Ghosh
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Transcriptional analysis of human peripheral blood mononuclear cells stimulated by Mycobacterium tuberculosis antigen
Jing Wei, Fangzheng Guo, Yamin Song, Kun Xu, Feiyang Lin, Kangsheng Li, Baiqing Li, Zhongqing Qian, Xiaojing Wang, Hongtao Wang, Tao Xu
Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef
Combining bioinformatics and machine learning algorithms to identify and analyze shared biomarkers and pathways in COVID-19 convalescence and diabetes mellitus
Jinru Shen, Yaolou Wang, Xijin Deng, Si Ri Gu Leng Sana
Frontiers in Endocrinology.2023;[Epub] CrossRef
Transcriptome analysis of peripheral blood mononuclear cells in patients with type 1 diabetes mellitus
Zhaoxiang Wang, Li Zhang, Fengyan Tang, Zhongming Yang, Mengzhu Wang, Jue Jia, Dong Wang, Ling Yang, Shao Zhong, Guoyue Yuan
Endocrine.2022; 78(2): 270. CrossRef

Metabolic Risk/Epidemiology
Current Status of Low-Density Lipoprotein Cholesterol Target Achievement in Patients with Type 2 Diabetes Mellitus in Korea Compared with Recent Guidelines: Soo Jin Yun, In-Kyung Jeong, Jin-Hye Cha, Juneyoung Lee, Ho Chan Cho, Sung Hee Choi, SungWan Chun, Hyun Jeong Jeon, Ho-Cheol Kang, Sang Soo Kim, Seung-Hyun Ko, Gwanpyo Koh, Su Kyoung Kwon, Jae Hyuk Lee, Min Kyong Moon, Junghyun Noh, Cheol-Young Park, Sungrae Kim; Diabetes Metab J. 2022;46(3):464-475. Published online March 3, 2022; DOI: https://doi.org/10.4093/dmj.2021.0088

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Background
We evaluated the achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with type 2 diabetes mellitus (T2DM) according to up-to-date Korean Diabetes Association (KDA), European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS), and American Diabetes Association (ADA) guidelines.
Methods
This retrospective cohort study collected electronic medical record data from patients with T2DM (≥20 years) managed by endocrinologists from 15 hospitals in Korea (January to December 2019). Patients were categorized according to guidelines to assess LDL-C target achievement. KDA (2019): Very High-I (atherosclerotic cardiovascular disease [ASCVD]) <70 mg/dL; Very High-II (target organ damage [TOD], or cardiovascular risk factors [CVRFs]) <70 mg/dL; high (others) <100 mg/dL. ESC/EAS (2019): Very High-I (ASCVD): <55 mg/dL; Very High-II (TOD or ≥3-CVRF) <55 mg/dL; high (diabetes ≥10 years without TOD plus any CVRF) <70 mg/dL; moderate (diabetes <10 years without CVRF) <100 mg/dL. ADA (2019): Very High-I (ASCVD); Very High-II (age ≥40+ TOD, or any CVRF), for high intensity statin or statin combined with ezetimibe.
Results
Among 2,000 T2DM patients (mean age 62.6 years; male 55.9%; mean glycosylated hemoglobin 7.2%) ASCVD prevalence was 24.7%. Of 1,455 (72.8%) patients treated with statins, 73.9% received monotherapy. According to KDA guidelines, LDL-C target achievement rates were 55.2% in Very High-I and 34.9% in Very High-II patients. With ESC/EAS guidelines, target attainment rates were 26.6% in Very High-I, 15.7% in Very High-II, and 25.9% in high risk patients. Based on ADA guidelines, most patients (78.9%) were very-high risk; however, only 15.5% received high-intensity statin or combination therapy.
Conclusion
According to current dyslipidemia management guidelines, LDL-C goal achievement remains suboptimal in Korean patients with T2DM.

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Umberto Capece, Chiara Iacomini, Teresa Mezza, Alfredo Cesario, Carlotta Masciocchi, Stefano Patarnello, Andrea Giaccari, Nicoletta Di Giorgi
Lipids in Health and Disease.2024;[Epub] CrossRef
Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factor
Nam Hoon Kim, Juneyoung Lee, Suk Chon, Jae Myung Yu, In-Kyung Jeong, Soo Lim, Won Jun Kim, Keeho Song, Ho Chan Cho, Hea Min Yu, Kyoung-Ah Kim, Sang Soo Kim, Soon Hee Lee, Chong Hwa Kim, Soo Heon Kwak, Yong‐ho Lee, Choon Hee Chung, Sihoon Lee, Heung Yong J
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ROsulord® sAfety for Patients with Dyslipidemia Study: A Non-interventional, Multicenter, Prospective, Observational Study in South Korea
Do Young Kim, Sung Hea Kim, Eung-Ju Kim, Sang-Jin Han, Ji-Yeong Park, Jong-Chan Youn, Hee-Seok Kim, Ji-Eun Jeong, Kyu-Hyung Ryu
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Diabetic Nephropathy: Pathogenesis, Mechanisms, and Therapeutic Strategies
Shivangi Dwivedi, Mukesh Singh Sikarwar
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Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
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Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
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Management of Dyslipidemia in Patients with Diabetes Mellitus
Kyung Ae Lee
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Association between carotid atherosclerosis and presence of intracranial atherosclerosis using three-dimensional high-resolution vessel wall magnetic resonance imaging in asymptomatic patients with type 2 diabetes
Ji Eun Jun, You-Cheol Hwang, Kyu Jeong Ahn, Ho Yeon Chung, Geon-Ho Jahng, Soonchan Park, In-Kyung Jeong, Chang-Woo Ryu
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Metabolic Risk/Epidemiology
Normalized Creatinine-to-Cystatin C Ratio and Risk of Diabetes in Middle-Aged and Older Adults: The China Health and Retirement Longitudinal Study: Shanhu Qiu, Xue Cai, Bo Xie, Yang Yuan, Zilin Sun, Tongzhi Wu; Diabetes Metab J. 2022;46(3):476-485. Published online March 7, 2022; DOI: https://doi.org/10.4093/dmj.2021.0074

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Background
Creatinine-to-cystatin C ratio is recently suggested to be a surrogate marker for sarcopenia. However, little is known about its association with diabetes. This study aimed to fill in this gap based on a large-scale prospective cohort.
Methods
A population-based representative sample of 5,055 participants aged ≥45 years from the China Health and Retirement Longitudinal Study was enrolled between 2011 and 2012 and followed at least once during the subsequent surveys at 2013, 2015, or 2018. Creatinine-to-cystatin C ratio was calculated and normalized by body weight. Incident diabetes was ascertained by plasma glucose, glycosylated hemoglobin, self-reported history, or use of anti-diabetic drugs. Logistic regression analysis and mediation analysis were employed.
Results
During follow-up, 634 participants developed diabetes. The risk of diabetes was gradually and significantly decreased with increased normalized creatinine–cystatin C ratio. The multivariable-adjusted odds ratio for diabetes was 0.91 (95% confidence interval, 0.83 to 0.99) per 1 standard deviation higher of normalized creatinine-to-cystatin C ratio, and this relationship remained significant after controlling for muscle strength. The risk reduction in diabetes was significantly larger in participants with normal-weight and high normalized creatinine-to-cystatin C ratio compared with those with overweight/obesity and high normalized creatinine-to-cystatin C ratio (P_interaction=0.01). Insulin resistance and inflammation appeared to be key mediators accounting for the observed relationship between normalized creatinine-to-cystatin C ratio and risk of diabetes, with their mediating effect being 93.1% and 22.0%, respectively.
Conclusion
High normalized creatinine-to-cystatin C ratio is associated with reduced risk of diabetes in middle-aged and older adults.

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Shanhu Qiu, Xue Cai, Xiaoying Zhou, Jinshui Xu, Zilin Sun, Haijian Guo, Tongzhi Wu
The Journal of Clinical Endocrinology & Metabolism.2024; 109(3): e1151. CrossRef
Sex‐specific associations between skeletal muscle mass and incident diabetes: A population‐based cohort study
Dan Liu, Nan Li, Yiling Zhou, Miye Wang, Peige Song, Changzheng Yuan, Qingyang Shi, Hui Chen, Kaixin Zhou, Huan Wang, Tao Li, Xiong‐Fei Pan, Haoming Tian, Sheyu Li
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Yun-Yun He, Mei-Ling Jin, Xiang-Yang Fang, Xiao-Juan Wang
Acta Diabetologica.2024; 61(7): 869. CrossRef
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Shixian Zhou, Peixia Wang, Linlin Sun, Xinxiu Zhao, Caixia Gong, Yichen Yang, Wen Ren, Yunmei Yang, Qin Zhang, JingJin Jiang
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Quhong Song, Taiping Lin, Rui Liang, Yanli Zhao, Ning Ge, Jirong Yue
BMC Geriatrics.2024;[Epub] CrossRef
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Jo-Hsuan Chen, Jau-Yuan Chen, Yi-Chuan Chen, Wen-Cheng Li
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Sex and Age Influence the Relationship Between Serum Creatinine/Cystatin C and Carotid Plaque in Patients With Type 2 Diabetes Mellitus
Dan Yang, Kexin Li, Qiujuan Zhang, Tian Yu, Ling Liu, You Wang, Shuyuan Kang, Shumiao Song, Baofeng Xu, Rui Liu
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Yinfei Chen, Weiheng Wen, Zhiliang Mai, Ming Wang, Hong Chen, Jia Sun
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Yun-Yun He, Mei-Ling Jin, Jing Chang, Xiao-Juan Wang
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Metabolic Risk/Epidemiology
Sex Differences of Visceral Fat Area and Visceral-to-Subcutaneous Fat Ratio for the Risk of Incident Type 2 Diabetes Mellitus: Eun Hee Kim, Hong-Kyu Kim, Min Jung Lee, Sung-Jin Bae, Jaewon Choe, Chang Hee Jung, Chul-Hee Kim, Joong-Yeol Park, Woo Je Lee; Diabetes Metab J. 2022;46(3):486-498. Published online November 18, 2021; DOI: https://doi.org/10.4093/dmj.2021.0095

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Background
This study aimed to determine the optimal cut-off values of visceral fat area (VFA) and visceral-to-subcutaneous fat ratio (VSR) for predicting incident type 2 diabetes mellitus (T2DM).
Methods
A total of 10,882 individuals (6,835 men; 4,047 women) free of T2DM at baseline aged between 30 and 79 years who underwent abdominal computed tomography scan between 2012 and 2013 as a part of routine health check-ups were included and followed. VFA, subcutaneous fat area, and VSR on L3 vertebral level were measured at baseline.
Results
During a median follow-up of 4.8 years, 730 (8.1% for men; 4.3% for women) incident cases of T2DM were identified. Receiver operating characteristic curve analysis showed that the optimal cut-off values of VFA and VSR for predicting incident T2DM were 130.03 cm² and 1.08 in men, respectively, and 85.7 cm² and 0.48 in women, respectively. Regardless of sex, higher VFA and VSR were significantly associated with a higher risk of incident T2DM. Compared with the lowest quartiles of VFA and VSR, the highest quartiles had adjusted odds ratios of 2.62 (95% confidence interval [CI], 1.73 to 3.97) and 1.55 (95% CI, 1.14 to 2.11) in men, respectively, and 32.49 (95% CI, 7.42 to 142.02) and 11.07 (95% CI, 3.89 to 31.50) in women, respectively.
Conclusion
Higher VFA and VSR at baseline were independent risk factors for the development of T2DM. Sex-specific reference values for visceral fat obesity (VFA ≥130 cm² or VSR ≥1.0 in men; VFA ≥85 cm² or VSR ≥0.5 in women) are proposed for the prediction of incident T2DM.

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Short Communications

Metabolic Risk/Epidemiology
Influence of Pre-Pregnancy Underweight Body Mass Index on Fetal Abdominal Circumference, Estimated Weight, and Pregnancy Outcomes in Gestational Diabetes Mellitus: Minji Kim, Kyu-Yeon Hur, Suk-Joo Choi, Soo-Young Oh, Cheong-Rae Roh; Diabetes Metab J. 2022;46(3):499-505. Published online January 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0059

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This study aimed to determine the influence of pre-pregnancy body mass index on pregnancy outcomes in gestational diabetes mellitus (GDM), comparing underweight patients with GDM with normal weight patients with GDM. Maternal baseline characteristics, ultrasonographic results, and pregnancy and neonatal outcomes were reviewed in 946 women with GDM with singleton pregnancies. Underweight patients with GDM showed a benign course in most aspects during pregnancy, except for developing a higher risk of giving birth to small for gestational age neonates. Underweight women with GDM required less insulin treatment, had a higher rate of vaginal delivery, and had a lower rate of cesarean delivery. In addition, their neonates were more likely to have fetal abdominal circumference and estimated fetal weight below the 10th percentile both at the time of GDM diagnosis and before delivery. Notably, their risk for preeclampsia and macrosomia were lower. Collectively, our data suggest that underweight women with GDM may require a different approach in terms of diagnosis and management throughout their pregnancy.

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Challenges in the management of gestational diabetes mellitus in anorexia nervosa
Rija Siddiqui, Carrie J McAdams
Psychiatry Research Case Reports.2024; 3(1): 100215. CrossRef
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Pradnyashree Wadivkar, Meredith Hawkins
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Obesity Is Associated With Higher Risk of Adverse Maternal and Neonatal Outcomes Than Supervised Gestational Diabetes
Namju Seo, You Min Lee, Ye-jin Kim, Ji-hee Sung, Kyu-Yeon Hur, Suk-Joo Choi, Cheong-Rae Roh, Soo-young Oh
Journal of Korean Medical Science.2023;[Epub] CrossRef
Maternal pre-pregnancy obesity modifies the association between first-trimester thyroid hormone sensitivity and gestational Diabetes Mellitus: a retrospective study from Northern China
Honglin Sun, Yibo Zhou, Jia Liu, Ying Wang, Guang Wang
Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef

Basic Research
GPR40 Agonism Modulates Inflammatory Reactions in Vascular Endothelial Cells: Joo Won Kim, Eun Roh, Kyung Mook Choi, Hye Jin Yoo, Hwan-Jin Hwang, Sei Hyun Baik; Diabetes Metab J. 2022;46(3):506-511. Published online January 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0092

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Endothelial dysfunction is strongly linked with inflammatory responses, which can impact cardiovascular disease. Recently, G protein-coupled receptor 40 (GPR40) has been investigated as a modulator of metabolic stress; however, the function of GPR40 in vascular endothelial cells has not been reported. We analyzed whether treatment of GPR40-specific agonists modulated the inflammatory responses in human umbilical vein endothelial cells (HUVECs). Treatment with LY2922470, a GPR40 agonist, significantly reduced lipopolysaccharide (LPS)-mediated nuclear factor-kappa B (NF-κB) phosphorylation and movement into the nucleus from the cytosol. However, treatment with another GPR40 agonist, TAK875, did not inhibit LPS-induced NF-κB activation. LPS treatment induced expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and attachment of THP-1 cells to HUVECs, which were all decreased by LY2922470 but not TAK875. Our results showed that ligand-dependent agonism of GPR40 is a promising therapeutic target for overcoming inflammatory reactions in the endothelium.

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Synthetic GPR40/FFAR1 agonists: An exhaustive survey on the most recent chemical classes and their structure-activity relationships
Abhik Paul, Sourin Nahar, Pankaj Nahata, Arnab Sarkar, Avik Maji, Ajeya Samanta, Sanmoy Karmakar, Tapan Kumar Maity
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Fengzhi Yu, Boyi Zong, Lili Ji, Peng Sun, Dandan Jia, Ru Wang
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Critical role of G protein-coupled receptor 40 in B cell response and the pathogenesis of rheumatoid arthritis in mice and patients
Anqi Li, Xiaoyi Wang, Jingwen Li, Xiaoyu Li, Jue Wang, Yang Liu, Zhihong Wang, Xiaobing Yang, Jiapeng Gao, Juanjie Wu, Tao Sun, Lixia Huo, Yanfeng Yi, Jiantong Shen, Jiexun Cai, Yunliang Yao
Cell Reports.2024; 43(10): 114858. CrossRef
GPR40 deficiency worsens metabolic syndrome‐associated periodontitis in mice
Yanchun Li, Zhongyang Lu, Cameron L. Kirkwood, Keith L. Kirkwood, Stephen A. Wank, Ai‐Jun Li, Maria F. Lopes‐Virella, Yan Huang
Journal of Periodontal Research.2023; 58(3): 575. CrossRef
Signaling pathways and intervention for therapy of type 2 diabetes mellitus
Rong Cao, Huimin Tian, Yu Zhang, Geng Liu, Haixia Xu, Guocheng Rao, Yan Tian, Xianghui Fu
MedComm.2023;[Epub] CrossRef
G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice
Yingyu Lu, Wanlu Zhou, Qinghua Cui, Chunmei Cui
International Journal of Molecular Sciences.2023; 24(15): 12244. CrossRef
AM1638, a GPR40-Full Agonist, Inhibited Palmitate- Induced ROS Production and Endoplasmic Reticulum Stress, Enhancing HUVEC Viability in an NRF2-Dependent Manner
Hwan-Jin Hwang, Joo Won Kim, SukHwan Yun, Min Jeong Park, Eyun Song, Sooyeon Jang, Ahreum Jang, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo
Endocrinology and Metabolism.2023; 38(6): 760. CrossRef
Learn from failures and stay hopeful to GPR40, a GPCR target with robust efficacy, for therapy of metabolic disorders
Hong-Ping Guan, Yusheng Xiong
Frontiers in Pharmacology.2022;[Epub] CrossRef

Letter

Association between Metabolic Syndrome and Microvascular Complications in Chinese Adults with Type 1 Diabetes Mellitus (Diabetes Metab J 2022;46:93-103): Gyuri Kim; Diabetes Metab J. 2022;46(3):512-514. Published online May 25, 2022; DOI: https://doi.org/10.4093/dmj.2022.0134

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