Diabetes & Metabolism Journal

Reviews

Guideline/Fact Sheet
Screening for Prediabetes and Diabetes in Korean Nonpregnant Adults: A Position Statement of the Korean Diabetes Association, 2022: Kyung Ae Lee, Dae Jung Kim, Kyungdo Han, Suk Chon, Min Kyong Moon, on Behalf of the Committee of Clinical Practice Guideline of Korean Diabetes Association; Diabetes Metab J. 2022;46(6):819-826. Published online November 24, 2022; DOI: https://doi.org/10.4093/dmj.2022.0364

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Diabetes screening serves to identify individuals at high-risk for diabetes who have not yet developed symptoms and to diagnose diabetes at an early stage. Globally, the prevalence of diabetes is rapidly increasing. Furthermore, obesity and/or abdominal obesity, which are major risk factors for type 2 diabetes mellitus (T2DM), are progressively increasing, particularly among young adults. Many patients with T2DM are asymptomatic and can accompany various complications at the time of diagnosis, as well as chronic complications develop as the duration of diabetes increases. Thus, proper screening and early diagnosis are essential for diabetes care. Based on reports on the changing epidemiology of diabetes and obesity in Korea, as well as growing evidence from new national cohort studies on diabetes screening, the Korean Diabetes Association has updated its clinical practice recommendations regarding T2DM screening. Diabetes screening is now recommended in adults aged ≥35 years regardless of the presence of risk factors, and in all adults (aged ≥19) with any of the risk factors. Abdominal obesity based on waist circumference (men ≥90 cm, women ≥85 cm) was added to the list of risk factors.

Citations

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Oxidative Balance Score and New-Onset Type 2 Diabetes Mellitus in Korean Adults without Non-Alcoholic Fatty Liver Disease: Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) Cohort
Mid-Eum Moon, Dong Hyuk Jung, Seok-Jae Heo, Byoungjin Park, Yong Jae Lee
Antioxidants.2024; 13(1): 107. CrossRef
Efficacy and Safety of Once-Weekly Semaglutide Versus Once-Daily Sitagliptin as Metformin Add-on in a Korean Population with Type 2 Diabetes
Byung-Wan Lee, Young Min Cho, Sin Gon Kim, Seung-Hyun Ko, Soo Lim, Amine Dahaoui, Jin Sook Jeong, Hyo Jin Lim, Jae Myung Yu
Diabetes Therapy.2024; 15(2): 547. CrossRef
Triglyceride-glucose index predicts type 2 diabetes mellitus more effectively than oral glucose tolerance test-derived insulin sensitivity and secretion markers
Min Jin Lee, Ji Hyun Bae, Ah Reum Khang, Dongwon Yi, Mi Sook Yun, Yang Ho Kang
Diabetes Research and Clinical Practice.2024; 210: 111640. CrossRef
Cumulative muscle strength and risk of diabetes: A prospective cohort study with mediation analysis
Shanhu Qiu, Xue Cai, Yan Liang, Wenji Chen, Duolao Wang, Zilin Sun, Bo Xie, Tongzhi Wu
Diabetes Research and Clinical Practice.2023; 197: 110562. CrossRef
Revisiting the Diabetes Crisis in Korea: Call for Urgent Action
Jun Sung Moon
The Journal of Korean Diabetes.2023; 24(1): 1. CrossRef
2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Nan Hee Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, YoonJu Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae J
Diabetes & Metabolism Journal.2023; 47(5): 575. CrossRef
2023 Clinical Practice Guidelines for Diabetes
Min Kyong Moon
The Journal of Korean Diabetes.2023; 24(3): 120. CrossRef

Pathophysiology
Blood Pressure Target in Type 2 Diabetes Mellitus: Hyun-Jin Kim, Kwang-il Kim, on Behalf of the Policy Committee of Korean Society of Hypertension; Diabetes Metab J. 2022;46(5):667-674. Published online September 19, 2022; DOI: https://doi.org/10.4093/dmj.2022.0215

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The prevalence of diabetes mellitus continues to increase worldwide, and it is a well-established cardiovascular risk factor. Hypertension is also an important cardiovascular risk factor to be controlled and is common among patients with diabetes mellitus. Optimal blood pressure (BP) goals have been the subject of great debate in the management of hypertension among patients with diabetes mellitus. This review provides detailed results from randomized controlled trials and meta-analyses of clinical outcomes according to the target BP in patients with type 2 diabetes mellitus. In addition, the target BP in patients with diabetes mellitus recommended by different guidelines was summarized and presented. A target BP of <140/90 mm Hg is recommended for patients with hypertension and diabetes mellitus, and BP should be controlled to <130/80 mm Hg in patients with diabetes mellitus who have high-risk clinical features. We hope that this review will be helpful to clinicians and patients by promoting the understanding and appropriate application of BP control in the comprehensive management of patients with diabetes mellitus.

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Emerging roles of interferon-stimulated gene-15 in age-related telomere attrition, the DNA damage response, and cardiovascular disease
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A diabetes update
Zachary Bloomgarden
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CARDIOPROTECTIVE AND METABOLIC EFFECTS OF ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH SUCH COMORBIDITIES AS ARTERIAL HYPERTENSION, TYPE 2 DIABETES MELLITUS, AND OBESITY
I. P. Dunaieva, N. O. Kravchun, І. A. Ilchenko
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Hypertensive Heart Failure
Filippos Triposkiadis, Pantelis Sarafidis, Alexandros Briasoulis, Dimitrios E. Magouliotis, Thanos Athanasiou, John Skoularigis, Andrew Xanthopoulos
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2023 Clinical Practice Guidelines for Diabetes
Min Kyong Moon
The Journal of Korean Diabetes.2023; 24(3): 120. CrossRef

Pathophysiology
Renoprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors: Focusing on Renal Hemodynamics: Nam Hoon Kim, Nan Hee Kim; Diabetes Metab J. 2022;46(4):543-551. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0209

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Diabetic kidney disease (DKD) is a prevalent renal complication of diabetes mellitus that ultimately develops into end-stage kidney disease (ESKD) when not managed appropriately. Substantial risk of ESKD remains even with intensive management of hyperglycemia and risk factors of DKD and timely use of renin-angiotensin-aldosterone inhibitors. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce hyperglycemia primarily by inhibiting glucose and sodium reabsorption in the renal proximal tubule. Currently, their effects expand to prevent or delay cardiovascular and renal adverse events, even in those without diabetes. In dedicated renal outcome trials, SGLT2 inhibitors significantly reduced the risk of composite renal adverse events, including the development of ESKD or renal replacement therapy, which led to the positioning of SGLT2 inhibitors as the mainstay of chronic kidney disease management. Multiple mechanisms of action of SGLT2 inhibitors, including hemodynamic, metabolic, and anti-inflammatory effects, have been proposed. Restoration of tubuloglomerular feedback is a plausible explanation for the alteration in renal hemodynamics induced by SGLT2 inhibition and for the associated renal benefit. This review discusses the clinical rationale and mechanism related to the protection SGLT2 inhibitors exert on the kidney, focusing on renal hemodynamic effects.

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Rethinking eGFR Comparisons in SGLT2 Inhibitor Research
Yuzuru Ohshiro
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SGLT2 Inhibitors and Diabetes: Where Does It Come from and Where Does It Go?
Ji Yoon Kim, Sin Gon Kim
The Journal of Korean Diabetes.2024; 25(1): 9. CrossRef
Baseline eGFR, albuminuria and renal outcomes in patients with SGLT2 inhibitor treatment: an updated meta-analysis
Yunke Ma, Chu Lin, Xiaoling Cai, Suiyuan Hu, Xingyun Zhu, Fang Lv, Wenjia Yang, Linong Ji
Acta Diabetologica.2023; 60(3): 435. CrossRef
Effects of sodium-glucose cotransporter 2 inhibitors on renal risk factors in patients with abnormal glucose metabolism: a meta-analysis of randomized controlled trials
Mengnan Li, Jian Zhang, Guimei Yang, Jiaxin Zhang, Minmin Han, Yi Zhang, Yunfeng Liu
European Journal of Clinical Pharmacology.2023; 79(6): 859. CrossRef
Age at Mortality in Patients with Type 2 Diabetes Who Underwent Kidney Transplantation: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018
Sun Ok Song, Eugene Han, Kang Ju Son, Bong-Soo Cha, Byung-Wan Lee
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Drug/Regimen
New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins: Kyuho Kim, Henry N. Ginsberg, Sung Hee Choi; Diabetes Metab J. 2022;46(4):517-532. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0198; Correction in: Diabetes Metab J 2022;46(5):817

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Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance in phase 2 trial, but the large clinical phase 3 trial (PROMINENT) was recently stopped for futility based on a late interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.

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Others
Current Trends of Big Data Research Using the Korean National Health Information Database: Mee Kyoung Kim, Kyungdo Han, Seung-Hwan Lee; Diabetes Metab J. 2022;46(4):552-563. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0193

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Recently, medical research using big data has become very popular, and its value has become increasingly recognized. The Korean National Health Information Database (NHID) is representative of big data that combines information obtained from the National Health Insurance Service collected for claims and reimbursement of health care services and results obtained from general health examinations provided to all Korean adults. This database has several strengths and limitations. Given the large size, various laboratory data, and questionnaires obtained from medical check-ups, their longitudinal nature, and long-term accumulation of data since 2002, carefully designed studies may provide valuable information that is difficult to obtain from other forms of research. However, consideration of possible bias and careful interpretation when defining causal relationships is also important because the data were not collected for research purposes. After the NHID became publicly available, research and publications based on this database have increased explosively, especially in the field of diabetes and metabolism. This article reviews the history, structure, and characteristics of the Korean NHID. Recent trends in big data research using this database, commonly used operational diagnosis, and representative studies have been introduced. We expect further progress and expansion of big data research using the Korean NHID.

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Pathophysiology
Endoplasmic Reticulum Stress and Dysregulated Autophagy in Human Pancreatic Beta Cells: Seoil Moon, Hye Seung Jung; Diabetes Metab J. 2022;46(4):533-542. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0070

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Pancreatic beta cell homeostasis is crucial for the synthesis and secretion of insulin; disruption of homeostasis causes diabetes, and is a treatment target. Adaptation to endoplasmic reticulum (ER) stress through the unfolded protein response (UPR) and adequate regulation of autophagy, which are closely linked, play essential roles in this homeostasis. In diabetes, the UPR and autophagy are dysregulated, which leads to beta cell failure and death. Various studies have explored methods to preserve pancreatic beta cell function and mass by relieving ER stress and regulating autophagic activity. To promote clinical translation of these research results to potential therapeutics for diabetes, we summarize the current knowledge on ER stress and autophagy in human insulin-secreting cells.

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Diabetes & Metabolism Journal.2024; 48(2): 231. CrossRef
Endoplasmic reticulum stress: A possible connection between intestinal inflammation and neurodegenerative disorders
Giorgio Vivacqua, Romina Mancinelli, Stefano Leone, Rosa Vaccaro, Ludovica Garro, Simone Carotti, Ludovica Ceci, Paolo Onori, Luigi Pannarale, Antonio Franchitto, Eugenio Gaudio, Arianna Casini
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Identification and analysis of type 2 diabetes-mellitus-associated autophagy-related genes
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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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Efficacy of convenience meal-type foods designed for diabetes in the management of metabolic syndrome based on a 3-week trial
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Medical nutrition therapy for diabetes mellitus
Suk Chon
Journal of the Korean Medical Association.2023; 66(7): 421. CrossRef

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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Xixi Han, Jingwen Kong, Hemin Zhang, Yuan Zhao, Yafeng Zheng, Chao Wei
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Patients with NAFLD exhibit more advanced fibrosis in liver biopsy than patients with other chronic liver diseases
Lydia Rohr, Peter Lemmer, Marie Henning, Andrea Tannapfel, Theodor Baars, Paul Manka, Ali Canbay, Jan-Peter Sowa
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Performance of Simple Fibrosis Score in Non-Alcoholic Fatty Liver Disease with and without Type 2 Diabetes
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Benefits of Physical Exercise as Approach to Prevention and Reversion of Non-Alcoholic Fatty Liver Disease in Children and Adolescents with Obesity
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Frontiers in Nutrition.2022;[Epub] CrossRef

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.

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Metabolic changes with intermittent fasting
Maria G. Lange, Alice A. Coffey, Paul C. Coleman, Thomas M. Barber, Thijs Van Rens, Oyinlola Oyebode, Sally Abbott, Petra Hanson
Journal of Human Nutrition and Dietetics.2024; 37(1): 256. CrossRef
Papel do Jejum Intermitente e da Dieta Restrita em Carboidratos na Prevenção de Doenças Cardiovasculares em Pacientes Pré-Diabéticos
Mohamed Khalfallah, Basma Elnagar, Shaimaa S. Soliman, Ahmad Eissa, Amany Allaithy
Arquivos Brasileiros de Cardiologia.2023;[Epub] CrossRef
Medical nutrition therapy for diabetes mellitus
Suk Chon
Journal of the Korean Medical Association.2023; 66(7): 421. CrossRef
Euglycemic diabetic ketoacidosis development in a patient with type 2 diabetes receiving a sodium-glucose cotransporter-2 inhibitor and a carbohydrate-restricted diet
Gwanpyo Koh, Jisun Bang, Soyeon Yoo, Sang Ah Lee
Journal of Medicine and Life Science.2023; 20(3): 126. CrossRef
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
Journal of Obesity & Metabolic Syndrome.2022; 31(3): 230. CrossRef

Others
Links between Thyroid Disorders and Glucose Homeostasis: Young Sil Eom, Jessica R. Wilson, Victor J. Bernet; Diabetes Metab J. 2022;46(2):239-256. Published online March 24, 2022; DOI: https://doi.org/10.4093/dmj.2022.0013

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Thyroid disorders and diabetes mellitus often coexist and are closely related. Several studies have shown a higher prevalence of thyroid disorders in patients with diabetes mellitus and vice versa. Thyroid hormone affects glucose homeostasis by impacting pancreatic β-cell development and glucose metabolism through several organs such as the liver, gastrointestinal tract, pancreas, adipose tissue, skeletal muscles, and the central nervous system. The present review discusses the effect of thyroid hormone on glucose homeostasis. We also review the relationship between thyroid disease and diabetes mellitus: type 1, type 2, and gestational diabetes, as well as guidelines for screening thyroid function with each disorder. Finally, we provide an overview of the effects of antidiabetic drugs on thyroid hormone and thyroid disorders.

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Metabolic Risk/Epidemiology
Not Control but Conquest: Strategies for the Remission of Type 2 Diabetes Mellitus: Jinyoung Kim, Hyuk-Sang Kwon; Diabetes Metab J. 2022;46(2):165-180. Published online March 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0377

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A durable normoglycemic state was observed in several studies that treated type 2 diabetes mellitus (T2DM) patients through metabolic surgery, intensive therapeutic intervention, or significant lifestyle modification, and it was confirmed that the functional β-cell mass was also restored to a normal level. Therefore, expert consensus introduced the concept of remission as a common term to express this phenomenon in 2009. Throughout this article, we introduce the recently updated consensus statement on the remission of T2DM in 2021 and share our perspective on the remission of diabetes. There is a need for more research on remission in Korea as well as in Western countries. Remission appears to be prompted by proactive treatment for hyperglycemia and significant weight loss prior to irreversible β-cell changes. T2DM is not a diagnosis for vulnerable individuals to helplessly accept. We attempt to explain how remission of T2DM can be achieved through a personalized approach. It may be necessary to change the concept of T2DM towards that of an urgent condition that requires rapid intervention rather than a chronic, progressive disease. We must grasp this paradigm shift in our understanding of T2DM for the benefit of our patients as endocrine experts.

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Diabetes, Obesity and Metabolism.2024; 26(2): 567. CrossRef
Mechanisms and the strategy for remission of type 2 diabetes mellitus
Tien‐Jyun Chang
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Complications
Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions: Md Jakir Hossain, Michael D. Kendig, Meg E. Letton, Margaret J. Morris, Ria Arnold; Diabetes Metab J. 2022;46(2):198-221. Published online March 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0347

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Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development.

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Multimodal Comparison of Diabetic Neuropathy in Aged Streptozotocin-Treated Sprague–Dawley and Zucker Diabetic Fatty Rats
Annalisa Canta, Valentina A. Carozzi, Alessia Chiorazzi, Cristina Meregalli, Norberto Oggioni, Virginia Rodriguez-Menendez, Barbara Sala, Roberto Cosimo Melcangi, Silvia Giatti, Raffaella Lombardi, Roberto Bianchi, Paola Marmiroli, Guido Cavaletti
Biomedicines.2022; 11(1): 20. CrossRef

Complications
Pathophysiologic Mechanisms and Potential Biomarkers in Diabetic Kidney Disease: Chan-Young Jung, Tae-Hyun Yoo; Diabetes Metab J. 2022;46(2):181-197. Published online March 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0329

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Although diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease eventually requiring chronic kidney replacement therapy, the prevalence of DKD has failed to decline over the past 30 years. In order to reduce disease prevalence, extensive research has been ongoing to improve prediction of DKD onset and progression. Although the most commonly used markers of DKD are albuminuria and estimated glomerular filtration rate, their limitations have encouraged researchers to search for novel biomarkers that could improve risk stratification. Considering that DKD is a complex disease process that involves several pathophysiologic mechanisms such as hyperglycemia induced inflammation, oxidative stress, tubular damage, eventually leading to kidney damage and fibrosis, many novel biomarkers that capture one specific mechanism of the disease have been developed. Moreover, the increasing use of high-throughput omic approaches to analyze biological samples that include proteomics, metabolomics, and transcriptomics has emerged as a strong tool in biomarker discovery. This review will first describe recent advances in the understanding of the pathophysiology of DKD, and second, describe the current clinical biomarkers for DKD, as well as the current status of multiple potential novel biomarkers with respect to protein biomarkers, proteomics, metabolomics, and transcriptomics.

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Pathophysiology
Glial and Vascular Cell Regulation of the Blood-Brain Barrier in Diabetes: Xiaolong Li, Yan Cai, Zuo Zhang, Jiyin Zhou; Diabetes Metab J. 2022;46(2):222-238. Published online March 18, 2022; DOI: https://doi.org/10.4093/dmj.2021.0146

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As a structural barrier, the blood-brain barrier (BBB) is located at the interface between the brain parenchyma and blood, and modulates communication between the brain and blood microenvironment to maintain homeostasis. The BBB is composed of endothelial cells, basement membrane, pericytes, and astrocytic end feet. BBB impairment is a distinguishing and pathogenic factor in diabetic encephalopathy. Diabetes causes leakage of the BBB through downregulation of tight junction proteins, resulting in impaired functioning of endothelial cells, pericytes, astrocytes, microglia, nerve/glial antigen 2-glia, and oligodendrocytes. However, the temporal regulation, mechanisms of molecular and signaling pathways, and consequences of BBB impairment in diabetes are not well understood. Consequently, the efficacy of therapies diabetes targeting BBB leakage still lags behind the requirements. This review summarizes the recent research on the effects of diabetes on BBB composition and the potential roles of glial and vascular cells as therapeutic targets for BBB disruption in diabetic encephalopathy.

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Metabolic Risk/Epidemiology
Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications: Joon Ho Moon, Hak Chul Jang; Diabetes Metab J. 2022;46(1):3-14. Published online January 27, 2022; DOI: https://doi.org/10.4093/dmj.2021.0335

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Gestational diabetes mellitus (GDM) is the most common complication during pregnancy and is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. GDM is associated with adverse pregnancy outcomes and long-term offspring and maternal complications. For GDM screening and diagnosis, a two-step approach (1-hour 50 g glucose challenge test followed by 3-hour 100 g oral glucose tolerance test) has been widely used. After the Hyperglycemia and Adverse Pregnancy Outcome study implemented a 75 g oral glucose tolerance test in all pregnant women, a one-step approach was recommended as an option for the diagnosis of GDM after 2010. The one-step approach has more than doubled the incidence of GDM, but its clinical benefit in reducing adverse pregnancy outcomes remains controversial. Long-term complications of mothers with GDM include type 2 diabetes mellitus and cardiovascular disease, and complications of their offspring include childhood obesity and glucose intolerance. The diagnostic criteria of GDM should properly classify women at risk for adverse pregnancy outcomes and long-term complications. The present review summarizes the strengths and weaknesses of the one-step and two-step approaches for the diagnosis of GDM based on recent randomized controlled trials and observational studies. We also describe the long-term maternal and offspring complications of GDM.

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