Diabetes & Metabolism Journal

Brief Reports

Metabolic Risk/Epidemiology
Short-Term Effects of the Internet-Based Korea Diabetes Prevention Study: 6-Month Results of a Community-Based Randomized Controlled Trial: Jin-Hee Lee, Sun-Young Lim, Seon-Ah Cha, Chan-Jung Han, Ah Reum Jung, Kook-Rye Kim, Kun-Ho Yoon, Seung-Hyun Ko; Diabetes Metab J. 2021;45(6):960-965. Published online March 17, 2021; DOI: https://doi.org/10.4093/dmj.2020.0225

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The aims of this study were to determine the short-term effectiveness of an internet-based lifestyle modification (LSM) program in preventing the onset of type 2 diabetes mellitus (T2DM) in prediabetes patients in community settings. A total of 415 subjects who were diagnosed with prediabetes were randomly assigned to the LSM and standard management (SM) groups. After the 6-month intervention, the LSM group had a statistically significant reduction in body weight, body mass index compared to the SM group participants. In the LSM group, blood glucose levels were significantly decreased after intervention and the clinical improvement effect was evident in the group that achieved the target weight loss of 5% or more of the initial weight for 6 months. Internet-based 6-month-intensive LSM programs conducted by public health center personnel are an effective way to provide lifestyle intervention programs and encourage maintenance of healthy behaviors in subjects with a high risk of T2DM in community settings.

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U-shaped association between online information exchange and app usage frequency: a large-scale survey of China ‘s online young and middle-aged people with pre diabetes and diabetes
Hanbin Guo, Yibiao Xiao, Canlin Liao, Jiating Sun, Yanchun Xie, Yitong Zheng, Guanhua Fan
Frontiers in Endocrinology.2023;[Epub] CrossRef
Innovation in diabetes prevention research: The 36-year legacy of China Da Qing diabetes prevention study
Xin Chai, Yachen Wang, Jinping Wang, Qiuhong Gong, Juan Zhang, Ruitai Shao
Chinese Science Bulletin.2023; 68(28-29): 3834. CrossRef
Efficacy of Personalized Diabetes Self-care Using an Electronic Medical Record–Integrated Mobile App in Patients With Type 2 Diabetes: 6-Month Randomized Controlled Trial
Eun Young Lee, Seon-Ah Cha, Jae-Seung Yun, Sun-Young Lim, Jin-Hee Lee, Yu-Bae Ahn, Kun-Ho Yoon, Min Kyung Hyun, Seung-Hyun Ko
Journal of Medical Internet Research.2022; 24(7): e37430. CrossRef
Prevention of type 2 diabetes through remotely administered lifestyle programs: A systematic review
Valaree Villegas, Alisha Shah, JoAnn E. Manson, Deirdre K. Tobias
Contemporary Clinical Trials.2022; 119: 106817. CrossRef
2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
Kyu Yeon Hur, Min Kyong Moon, Jong Suk Park, Soo-Kyung Kim, Seung-Hwan Lee, Jae-Seung Yun, Jong Ha Baek, Junghyun Noh, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Ye Seul Yang, Jang Won Son, Jong Han Choi, Kee Ho Song, Nam Hoon Kim, Sang Yong Kim, Jin Wha Kim,
Diabetes & Metabolism Journal.2021; 45(4): 461. CrossRef
2021 Clinical Practice Guidelines for Diabetes Mellitus in Korea
Seung-Hyun Ko
The Journal of Korean Diabetes.2021; 22(4): 244. CrossRef

Drug/Regimen
Long-Term Glycaemic Durability of Early Combination Therapy Strategy versus Metformin Monotherapy in Korean Patients with Newly Diagnosed Type 2 Diabetes Mellitus: Soon-Jib Yoo, Sang-Ah Chang, Tae Seo Sohn, Hyuk-Sang Kwon, Jong Min Lee, Sungdae Moon, Pieter Proot, Päivi M Paldánius, Kun Ho Yoon; Diabetes Metab J. 2021;45(6):954-959. Published online November 12, 2020; DOI: https://doi.org/10.4093/dmj.2020.0173

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We assessed the glycaemic durability with early combination (EC; vildagliptin+metformin [MET], n=22) versus MET monotherapy (n=17), among newly-diagnosed type 2 diabetes mellitus (T2DM) enrolled (between 2012 and 2014) in the VERIFY study from Korea (n=39). Primary endpoint was time to initial treatment failure (TF) (glycosylated hemoglobin [HbA1c] ≥7.0% at two consecutive scheduled visits after randomization [end of period 1]). Time to second TF was assessed when both groups were receiving and failing on the combination (end of period 2). With EC the risk of initial TF significantly reduced by 78% compared to MET (n=3 [15%] vs. n=10 [58.7%], P=0.0228). No secondary TF occurred in EC group versus five patients (29.4%) in MET. Patients receiving EC treatment achieved consistently lower HbA1c levels. Both treatment approaches were well tolerated with no hypoglycaemic events. In Korean patients with newly diagnosed T2DM, EC treatment significantly and consistently improved the long-term glycaemic durability as compared with MET.

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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
2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
Kyu Yeon Hur, Min Kyong Moon, Jong Suk Park, Soo-Kyung Kim, Seung-Hwan Lee, Jae-Seung Yun, Jong Ha Baek, Junghyun Noh, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Ye Seul Yang, Jang Won Son, Jong Han Choi, Kee Ho Song, Nam Hoon Kim, Sang Yong Kim, Jin Wha Kim,
Diabetes & Metabolism Journal.2021; 45(4): 461. CrossRef

Short Communication

Drug/Regimen
Dulaglutide as an Effective Replacement for Prandial Insulin in Kidney Transplant Recipients with Type 2 Diabetes Mellitus: A Retrospective Review: Hwi Seung Kim, Jiwoo Lee, Chang Hee Jung, Joong-Yeol Park, Woo Je Lee; Diabetes Metab J. 2021;45(6):948-953. Published online February 5, 2021; DOI: https://doi.org/10.4093/dmj.2020.0180

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Dulaglutide, a weekly injectable glucagon-like peptide-1 receptor agonist, has demonstrated effectiveness when combined with basal insulin. We examined whether the efficacy of dulaglutide is comparable to that of prandial insulin in kidney transplant (KT) recipients with type 2 diabetes mellitus (T2DM) undergoing multiple daily insulin injection (MDI) therapy. Thirty-seven patients, who switched from MDI therapy to basal insulin and dulaglutide, were retrospectively analyzed. Changes in glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels, body weight, and basal insulin dose were evaluated over 6 months. Dulaglutide was comparable to three injections of prandial insulin in terms of glycemic control (HbA1c 7.1% vs. 7.0%; 95% confidence interval [CI], –0.53 to 0.28; P=0.53). The basal insulin and dulaglutide combination resulted in a reduction in FPG levels by 9.7 mg/dL (95% CI, 2.09 to 41.54; P=0.03), in body weight by 4.9 kg (95% CI, 2.87 to 6.98; P<0.001), and in basal insulin dose by 9.52 IU (95% CI, 5.80 to 3.23; P<0.001). Once-weekly dulaglutide may be an effective alternative for thrice-daily prandial insulin in KT recipients with T2DM currently receiving MDI therapy.

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Diabetic Kidney Disease in Post-Kidney Transplant Patients
Ngoc-Yen T. Pham, Diego Cruz, Luis Madera-Marin, Raja Ravender, Pablo Garcia
Journal of Clinical Medicine.2024; 13(3): 793. CrossRef
Safety and efficacy of glucagon-like peptide-1 receptor agonists among kidney transplant recipients: a systematic review and meta-analysis
Pajaree Krisanapan, Supawadee Suppadungsuk, Kanokporn Sanpawithayakul, Charat Thongprayoon, Pattharawin Pattharanitima, Supawit Tangpanithandee, Michael A Mao, Jing Miao, Wisit Cheungpasitporn
Clinical Kidney Journal.2024;[Epub] CrossRef
Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post‐transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation
S. Elise Lawrence, Mary Moss Chandran, Jeong M. Park, Helen Sweiss, Thomas Jensen, Palak Choksi, Barrett Crowther
Clinical Transplantation.2023;[Epub] CrossRef
Novel Drugs for the Management of Diabetes Kidney Transplant Patients: A Literature Review
Nancy Daniela Valencia-Morales, Beatriz Rodríguez-Cubillo, Rómulo Katsu Loayza-López, Maria Ángeles Moreno de la Higuera, Ana Isabel Sánchez-Fructuoso
Life.2023; 13(6): 1265. CrossRef
Uso de los agonistas del receptor del péptido similar al glucagón tipo 1 en pacientes trasplantados renales
Luis Alberto Vigara, Florentino Villanego, Cristhian Orellana, Myriam Eady, María Gabriela Sánchez, Marta Alonso, María Belén García, José Manuel Amaro, Teresa García, Auxiliadora Mazuecos
Nefrología.2023;[Epub] CrossRef
Tolerability and Effectiveness of Switching to Dulaglutide in Patients With Type 2 Diabetes Inadequately Controlled With Insulin Therapy
Youngsook Kim, Ji Hye Huh, Minyoung Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee
Frontiers in Endocrinology.2022;[Epub] CrossRef

Original Articles

Basic Research
Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway: Jung-Hee Hong, Moon-Kyu Lee; Diabetes Metab J. 2021;45(6):933-947. Published online August 19, 2021; DOI: https://doi.org/10.4093/dmj.2020.0223

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Background
Carnitine orotate complex (Godex) has been shown to decrease glycated hemoglobin levels and improve steatosis in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease. However, the mechanisms of Godex in glucose metabolism remain unclear.
Methods
Male C57BL/6J mice were divided into four groups: normal-fat diet, high-fat diet, a high-fat diet supplemented with intraperitoneal injection of (500 mg or 2,000 mg/kg/day) Godex for 8 weeks. Computed tomography, indirect calorimetry, and histological analyses including electron microscopy of the liver were performed, and biochemical profiles and oral glucose tolerance test and insulin tolerance test were undertaken. Expressions of genes in the lipid and glucose metabolism, activities of oxidative phosphorylation enzymes, carnitine acetyltransferase, pyruvate dehydrogenase, and acetyl-coenzyme A (CoA)/CoA ratio were evaluated.
Results
Godex improved insulin sensitivity and significantly decreased fasting plasma glucose, homeostatic model assessment for insulin resistance, steatosis, and gluconeogenesis, with a marked increase in fatty acid oxidation as well as better use of glucose in high-fat diet-fed mice. It preserved mitochondrial function and ultrastructure, restored oxidative phosphorylation enzyme activities, decreased acetyl-CoA/CoA ratio, and increased carnitine acetyltransferase content and pyruvate dehydrogenase activity. Carnitine acetyltransferase knockdown partially reversed the effects of Godex in liver and in vitro.
Conclusion
Godex improved insulin resistance and steatosis by regulating carnitine acetyltransferase in liver in high-fat diet-fed mice.

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Impact of l-Carnitine Supplementation on Liver Enzyme Normalization in Patients with Chronic Liver Disease: A Meta-Analysis of Randomized Trials
Hyunwoo Oh, Chan Hyuk Park, Dae Won Jun
Journal of Personalized Medicine.2022; 12(7): 1053. CrossRef
Prolonged Use of Carnitine-Orotate Complex (Godex®) Is Associated with Improved Mortality: A Nationwide Cohort Study
Kye-Yeung Park, Sangmo Hong, Kyung-Soo Kim, Kyungdo Han, Cheol-Young Park
Journal of Personalized Medicine.2022; 12(12): 1970. CrossRef
The Role of Carnitine Orotate Complex in Fatty Liver
Hyon-Seung Yi
Diabetes & Metabolism Journal.2021; 45(6): 866. CrossRef

Basic Research
Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway: Ji-Yeon Lee, Minyoung Lee, Ji Young Lee, Jaehyun Bae, Eugene Shin, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha; Diabetes Metab J. 2021;45(6):921-932. Published online February 22, 2021; DOI: https://doi.org/10.4093/dmj.2020.0187

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Background
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism.
Methods
Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks.
Results
The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue.
Conclusion
SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.

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SGLT2 inhibitors and AMPK: The road to cellular housekeeping?
Nasser Safaie, Shahab Masoumi, Shaban Alizadeh, Pourya Mirzajanzadeh, Hamid Reza Nejabati, Mobasher Hajiabbasi, Vahid Alivirdiloo, Neda Chobdari Basmenji, Aysan Derakhshi Radvar, Ziba Majidi, Yousef Faridvand
Cell Biochemistry and Function.2024;[Epub] CrossRef
Mechanisms of SGLT2 Inhibitors in Heart Failure and Their Clinical Value
Yafei Xie, Yujie Wei, Dan Li, Jie Pu, Hong Ding, Xiaowei Zhang
Journal of Cardiovascular Pharmacology.2023; 81(1): 4. CrossRef
Current Treatment Options, Including Diet, Exercise, and Medications
Mazen Noureddin, Manal F. Abdelmalek
Clinics in Liver Disease.2023; 27(2): 397. CrossRef
SGLT2 Inhibitors and Kidney Diseases: A Clinical Perspective
Panagiotis Theofilis, Rigas G. Kalaitzidis
Current Medicinal Chemistry.2023; 30(23): 2595. CrossRef
Treatment of obesity-related diabetes: significance of thermogenic adipose tissue and targetable receptors
Ruping Pan, Jiadai Liu, Yong Chen
Frontiers in Pharmacology.2023;[Epub] CrossRef
Immunomodulatory Effects of SGLT2 Inhibitors—Targeting Inflammation and Oxidative Stress in Aging
Ema Schönberger, Vjera Mihaljević, Kristina Steiner, Sandra Šarić, Tomislav Kurevija, Ljiljana Trtica Majnarić, Ines Bilić Ćurčić, Silvija Canecki-Varžić
International Journal of Environmental Research and Public Health.2023; 20(17): 6671. CrossRef
SGLT‐2 inhibitors enhance the effect of metformin to ameliorate hormonal changes and inflammatory markers in a rat PCOS model
Manal Moustafa Mahmoud, Laila Ahmed Rashed, Somia Abdulatif Soliman, Safaa Mostafa Sayed, Omneya Kamel, Samaa Samir Kamar, Rania El Sayed Hussien
Physiological Reports.2023;[Epub] CrossRef
Resting energy expenditure based on equation estimation can predict renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease
Xiang Xiao, Shuming Ji, Junlin Zhang, Deying Kang, Fang Liu
Renal Failure.2023;[Epub] CrossRef
Sodium-glucose Cotransporter 2 Inhibitors and Pathological Myocardial Hypertrophy
Zhicheng Gao, Jiaqi Bao, Yilan Hu, Junjie Tu, Lifang Ye, Lihong Wang
Current Drug Targets.2023; 24(13): 1009. CrossRef
SIRT1 mediates the inhibitory effect of Dapagliflozin on EndMT by inhibiting the acetylation of endothelium Notch1
Weijie Wang, Yilan Li, Yanxiu Zhang, Tao Ye, Kui Wang, Shuijie Li, Yao Zhang
Cardiovascular Diabetology.2023;[Epub] CrossRef
Direct cardio-protection of Dapagliflozin against obesity-related cardiomyopathy via NHE1/MAPK signaling
Ke Lin, Na Yang, Wu Luo, Jin-fu Qian, Wei-wei Zhu, Shi-ju Ye, Chen-xin Yuan, Di-yun Xu, Guang Liang, Wei-jian Huang, Pei-ren Shan
Acta Pharmacologica Sinica.2022; 43(10): 2624. CrossRef
Pleiotropic effects of SGLT2 inhibitors and heart failure outcomes
Panagiotis Theofilis, Marios Sagris, Evangelos Oikonomou, Alexios S. Antonopoulos, Gerasimos Siasos, Kostas Tsioufis, Dimitris Tousoulis
Diabetes Research and Clinical Practice.2022; 188: 109927. CrossRef
Role of Sodium-Glucose Co-Transporter 2 Inhibitors in the Regulation of Inflammatory Processes in Animal Models
Sandra Feijóo-Bandín, Alana Aragón-Herrera, Manuel Otero-Santiago, Laura Anido-Varela, Sandra Moraña-Fernández, Estefanía Tarazón, Esther Roselló-Lletí, Manuel Portolés, Oreste Gualillo, José Ramón González-Juanatey, Francisca Lago
International Journal of Molecular Sciences.2022; 23(10): 5634. CrossRef
Potential molecular mechanism of action of sodium-glucose co-transporter 2 inhibitors in the prevention and management of diabetic retinopathy
Lia Meuthia Zaini, Arief S Kartasasmita, Tjahjono D Gondhowiardjo, Maimun Syukri, Ronny Lesmana
Expert Review of Ophthalmology.2022; 17(3): 199. CrossRef
New insights and advances of sodium-glucose cotransporter 2 inhibitors in heart failure
Juexing Li, Lei Zhou, Hui Gong
Frontiers in Cardiovascular Medicine.2022;[Epub] CrossRef
Critical Reanalysis of the Mechanisms Underlying the Cardiorenal Benefits of SGLT2 Inhibitors and Reaffirmation of the Nutrient Deprivation Signaling/Autophagy Hypothesis
Milton Packer
Circulation.2022; 146(18): 1383. CrossRef
Nutraceutical activation of Sirt1: a review
James J DiNicolantonio, Mark F McCarty, James H O'Keefe
Open Heart.2022; 9(2): e002171. CrossRef
Dapagliflozin Restores Impaired Autophagy and Suppresses Inflammation in High Glucose-Treated HK-2 Cells
Jing Xu, Munehiro Kitada, Yoshio Ogura, Haijie Liu, Daisuke Koya
Cells.2021; 10(6): 1457. CrossRef
Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations
Dimitrios A. Vrachatis, Konstantinos A. Papathanasiou, Konstantinos E. Iliodromitis, Sotiria G. Giotaki, Charalampos Kossyvakis, Konstantinos Raisakis, Andreas Kaoukis, Vaia Lambadiari, Dimitrios Avramides, Bernhard Reimers, Giulio G. Stefanini, Michael C
Drugs.2021; 81(12): 1381. CrossRef
Differential Pathophysiological Mechanisms in Heart Failure With a Reduced or Preserved Ejection Fraction in Diabetes
Milton Packer
JACC: Heart Failure.2021; 9(8): 535. CrossRef
Ketone bodies: from enemy to friend and guardian angel
Hubert Kolb, Kerstin Kempf, Martin Röhling, Martina Lenzen-Schulte, Nanette C. Schloot, Stephan Martin
BMC Medicine.2021;[Epub] CrossRef

Basic Research
Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7: Lili Kong, Hongyue Wang, Chenhao Li, Huiyan Cheng, Yan Cui, Li Liu, Ying Zhao; Diabetes Metab J. 2021;45(6):909-920. Published online June 4, 2021; DOI: https://doi.org/10.4093/dmj.2020.0168

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Background
The dietary agent sulforaphane (SFN) has been reported to reduce diabetes-induced renal fibrosis, as well as inhibit histone deacetylase (HDAC) activity. Bone morphologic protein 7 (BMP-7) has been shown to reduce renal fibrosis induced by transforming growth factor-beta1. The aim of this study was to investigate the epigenetic effect of SFN on BMP-7 expression in diabetes-induced renal fibrosis.
Methods
Streptozotocin (STZ)-induced diabetic mice and age-matched controls were subcutaneously injected with SFN or vehicle for 4 months to measure the in vivo effects of SFN on the kidneys. The human renal proximal tubular (HK11) cell line was used to mimic diabetic conditions in vitro. HK11 cells were transfected to over-express HDAC2 and treated with high glucose/palmitate (HG/Pal) to explore the epigenetic modulation of BMP-7 in SFN-mediated protection against HG/Pal-induced renal fibrosis.
Results
SFN significantly attenuated diabetes-induced renal fibrosis in vivo. Among all of the HDACs we detected, HDAC2 activity was markedly elevated in the STZ-induced diabetic kidneys and HG/Pal-treated HK11 cells. SFN inhibited the diabetes-induced increase in HDAC2 activity which was associated with histone acetylation and transcriptional activation of the BMP-7 promoter. HDAC2 over-expression reduced BMP-7 expression and abolished the SFN-mediated protection against HG/Pal-induced fibrosis in vitro.
Conclusion
Our study demonstrates that the HDAC inhibitor SFN protects against diabetes-induced renal fibrosis through epigenetic up-regulation of BMP-7.

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Sulforaphane reduces adipose tissue fibrosis via promoting M2 macrophages polarization in HFD fed-mice
Zhenzhen Zhang, Huali Chen, Cheng Pan, Rui Li, Wangsheng Zhao, Tianzeng Song
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2024; 1871(2): 119626. CrossRef
Potential of Plant-Derived Compounds in Preventing and Reversing Organ Fibrosis and the Underlying Mechanisms
Patrícia dos Santos Azeredo, Daping Fan, E. Angela Murphy, Wayne E. Carver
Cells.2024; 13(5): 421. CrossRef
Beneficial role of broccoli and its active ingredient, sulforaphane in the treatment of diabetes
Aminu Mohammed, Hafsat Abdullahi Mohammed
Phytomedicine Plus.2023; 3(2): 100431. CrossRef
The Role of Histone Modifications in the Pathogenesis of Diabetic Kidney Disease
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International Journal of Molecular Sciences.2023; 24(6): 6007. CrossRef
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Da-Wei Lin, Yung-Chien Hsu, Cheng-Chih Chang, Ching-Chuan Hsieh, Chun-Liang Lin
International Journal of Molecular Sciences.2023; 24(7): 6053. CrossRef
Beneficial Effects of Sulforaphane on Diabetes and Its Complications via Both Nrf2-Dependent and Independent Mechanisms
Minhyuk Kim, Joo Young Lee
Food Supplements and Biomaterials for Health.2023;[Epub] CrossRef
Sulforaphane exhibits potent renoprotective effects in preclinical models of kidney diseases: A systematic review and meta-analysis
Elisa B. Monteiro, Matheus Ajackson, Milena B. Stockler-Pinto, Fitsum Guebre-Egziabher, Julio B. Daleprane, Christophe O. Soulage
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Hongzhou Lin, Huihui Chen, Rengcheng Qian, Guoqi Tang, Yinjuan Ding, Yalan Jiang, Congde Chen, Dexuan Wang, Maoping Chu, Xiaoling Guo
Chemico-Biological Interactions.2023; 382: 110559. CrossRef
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Tao Jiang, Yuhe Dong, Wanying Zhu, Tong Wu, Linyan Chen, Yuantong Cao, Xi Yu, Ye Peng, Ling Wang, Ying Xiao, Tian Zhong
Critical Reviews in Food Science and Nutrition.2023; : 1. CrossRef
Sulforaphane: A nutraceutical against diabetes-related complications
Sinenhlanhla X.H. Mthembu, Sithandiwe E. Mazibuko-Mbeje, Marakiya T. Moetlediwa, Ndivhuwo Muvhulawa, Sonia Silvestri, Patrick Orlando, Bongani B. Nkambule, Christo J.F. Muller, Duduzile Ndwandwe, Albertus K. Basson, Luca Tiano, Phiwayinkosi V. Dludla
Pharmacological Research.2023; 196: 106918. CrossRef
Nrf2/HO-1 as a therapeutic target in renal fibrosis
Emad H.M. Hassanein, Islam M. Ibrahim, Esraa K. Abd-alhameed, Zeina W. Sharawi, Fatima A. Jaber, Hanan S. Althagafy
Life Sciences.2023; 334: 122209. CrossRef
A mechanistic overview of sulforaphane and its derivatives application in diabetes and its complications
Neda Mohamadi, Vafa Baradaran Rahimi, Mohammad Reza Fadaei, Fatemeh Sharifi, Vahid Reza Askari
Inflammopharmacology.2023; 31(6): 2885. CrossRef
The HDAC2/SP1/miR-205 feedback loop contributes to tubular epithelial cell extracellular matrix production in diabetic kidney disease
Zongji Zheng, Shuting Zhang, Jiaqi Chen, Meina Zou, Yanlin Yang, Wen Lu, Shijing Ren, Xiangyu Wang, Wenhui Dong, Zikun Zhang, Ling Wang, Meiping Guan, Gladys L.Y. Cheing, Yaoming Xue, Yijie Jia
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BMP-7 Upregulates Id2 Through the MAPK Signaling Pathway to Improve Diabetic Tubulointerstitial Fibrosis and the Intervention of Oxymatrine
Yawen Xiao, Dan Liang, Zhiyang Li, Zhaowei Feng, Zhiping Yuan, Fan Zhang, Yuanyuan Wang, Yuxia Zhou, Mingjun Shi, Lingling Liu, Ying Xiao, Bing Guo
Frontiers in Pharmacology.2022;[Epub] CrossRef
HDAC1 Promotes Myocardial Fibrosis in Diabetic Cardiomyopathy by Inhibiting BMP-7 Transcription Through Histone Deacetylation
Chun Ouyang, Lei Huang, Xiaoqiang Ye, Mingming Ren, Zhen Han
Experimental and Clinical Endocrinology & Diabetes.2022; 130(10): 660. CrossRef
Class IIa histone deacetylase inhibition ameliorates acute kidney injury by suppressing renal tubular cell apoptosis and enhancing autophagy and proliferation
Jialu Li, Chao Yu, Fengchen Shen, Binbin Cui, Na Liu, Shougang Zhuang
Frontiers in Pharmacology.2022;[Epub] CrossRef
Molecular mechanisms of histone deacetylases and inhibitors in renal fibrosis progression
Jiayu Wang, Jiaxing Li, Xin Zhang, Min Zhang, Xiaopeng Hu, Hang Yin
Frontiers in Molecular Biosciences.2022;[Epub] CrossRef
The improvement of sulforaphane in type 2 diabetes mellitus (T2DM) and related complications: A review
Mengjiao Wang, Min Chen, Rui Guo, Yangyang Ding, Haihui Zhang, Yuanqing He
Trends in Food Science & Technology.2022; 129: 397. CrossRef
Defining therapeutic targets for renal fibrosis: Exploiting the biology of pathogenesis
Hao Yan, Jiangxin Xu, Zhifei Xu, Bo Yang, Peihua Luo, Qiaojun He
Biomedicine & Pharmacotherapy.2021; 143: 112115. CrossRef

Genetics
The rs2304256 Polymorphism in TYK2 Gene Is Associated with Protection for Type 1 Diabetes Mellitus: Felipe Mateus Pellenz, Cristine Dieter, Guilherme Coutinho Kullmann Duarte, Luís Henrique Canani, Bianca Marmontel de Souza, Daisy Crispim; Diabetes Metab J. 2021;45(6):899-908. Published online May 24, 2021; DOI: https://doi.org/10.4093/dmj.2020.0194

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Background
Tyrosine kinase 2 (TYK2) is a candidate gene for type 1 diabetes mellitus (T1DM) since it plays an important role in regulating apoptotic and pro-inflammatory pathways in pancreatic β-cells through modulation of the type I interferon signaling pathway. The rs2304256 single nucleotide polymorphism (SNP) in TYK2 gene has been associated with protection for different autoimmune diseases. However, to date, only two studies have evaluated the association between this SNP and T1DM, with discordant results. This study thus aimed to investigate the association between the TYK2 rs2304256 SNP and T1DM in a Southern Brazilian population.
Methods
This case-control study comprised 478 patients with T1DM and 518 non-diabetic subjects. The rs2304256 (C/A) SNP was genotyped by real-time polymerase chain reaction technique using TaqMan minor groove binder (MGB) probes.
Results
Genotype and allele frequencies of the rs2304256 SNP differed between T1DM patients and non-diabetic subjects (P<0.0001 and P=0.001, respectively). Furthermore, the A allele was associated with protection against T1DM under recessive (odds ratio [OR], 0.482; 95% confidence interval [CI], 0.288 to 0.806) and additive (OR, 0.470; 95% CI, 0.278 to 0.794) inheritance models, adjusting for human leukocyte antigen (HLA) DR/DQ genotypes, gender, and ethnicity.
Conclusion
The A/A genotype of TYK2 rs2304256 SNP is associated with protection against T1DM in a Southern Brazilian population.

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Metabolic Risk/Epidemiology
Increased Visit-to-Visit Liver Enzyme Variability Is Associated with Incident Diabetes: A Community-Based 12-Year Prospective Cohort Study: Kyuhoon Bang, Ji Eun Jun, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung, You-Cheol Hwang; Diabetes Metab J. 2021;45(6):890-898. Published online March 17, 2021; DOI: https://doi.org/10.4093/dmj.2020.0208

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub: Background
Fatty liver and/or increased liver enzyme values have been reported to be associated with incident diabetes. We sought to determine whether increased visit-to-visit liver enzyme variability is associated with incident diabetes.
Methods
Study participants were recruited from the Korean Genome and Epidemiologic Study (KoGES). A total of 4,151 people aged 40 to 69 years was recruited and tested every 2 years for up to 12 years. Visit-to-visit aspartate aminotransferase (AST) and alanine aminotransferase (ALT) variability was evaluated in first the 6-year period through the use of various variability measurements: standard deviation (SD), average successive variability, coefficient of variation (CV), and variation independent of mean (VIM). Oral glucose tolerance test was performed at every visit.
Results
During the 6-year follow‐up appointments, 13.0% (538/4,151) of people developed incident diabetes. Visit-to-visit AST variability was associated with an increased risk of diabetes independent of conventional risk factors for diabetes (hazard ratio per 1-SD increment [95% confidence interval]: 1.06 [1.00 to 1.11], 1.12 [1.04 to 1.21], and 1.13 [1.04 to 1.22] for SD, CV, and VIM, respectively; all P<0.05); however, no such associations were observed in the visit-to-visit ALT variability. According to alcohol consumption status, both AST and ALT variability were independent predictors for incident diabetes in subjects with heavy alcohol consumption; however, neither AST nor ALT variability was associated with diabetes risk in subjects who did not drink alcohol heavily.
Conclusion
Visit-to-visit liver enzyme variability is an independent predictor of incident diabetes. Such association was more evident in those who consumed significant amounts of alcohol.

Metabolic Risk/Epidemiology
Trends and Risk Factors of Metabolic Syndrome among Korean Adolescents, 2007 to 2018: Jiun Chae, Moon Young Seo, Shin-Hye Kim, Mi Jung Park; Diabetes Metab J. 2021;45(6):880-889. Published online July 6, 2021; DOI: https://doi.org/10.4093/dmj.2020.0185

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Background
There is a lack of recent research on the changes in risk factors for metabolic syndrome (MetS) in the Asian pediatric population. We aimed to determine the 12-year trends in the prevalence of MetS and relevant lifestyle factors such as smoking, exercise, and calorie intake among Korean adolescents.
Methods
We investigated trends in MetS and lifestyle factors among 6,308 adolescents aged 12 to 18 years from the Korea National Health and Nutrition Examination Survey, 2007 to 2018.
Results
The prevalence of MetS was stable from 2007 to 2018 (1.7% to 2.2%). There were significant increases in the prevalence of central obesity (from 8.1% to 11.2%, P=0.012) and hyperglycemia (from 5.3% to 10.4%, P<0.001) and decreases in hypo-high-density lipoprotein (HDL)-cholesterolemia (from 22.4% to 14.8%, P<0.001). Total calorie intake and calorie intake from fat significantly increased (P<0.001), whereas calorie intake from carbohydrates significantly decreased (P<0.001) during the study period. The proportions of tobacco smokers and regular walkers significantly decreased from 2007 to 2018. After controlling for all covariates, total calorie intake was positively correlated with waist circumference (P<0.05). HDL-cholesterol was negatively associated with carbohydrate consumption (P<0.01) and positively associated with fat consumption (P<0.001). Regular walking and regular strength training were associated with lower waist circumference (P<0.05). Smoking was associated with lower fasting glucose levels (P<0.01).
Conclusion
Although the prevalence rate of MetS is stable among Korean adolescents, the prevalence of central obesity and hyperglycemia has increased greatly in the recent decade. Public education on proper dietary intake and lifestyle modification is required.

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Complications
Associations of Plasma Glucagon Levels with Estimated Glomerular Filtration Rate, Albuminuria and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus: Hua-Xing Huang, Liang-Lan Shen, Hai-Yan Huang, Li-Hua Zhao, Feng Xu, Dong-Mei Zhang, Xiu-Lin Zhang, Tong Chen, Xue-Qin Wang, Yan Xie, Jian-Bin Su; Diabetes Metab J. 2021;45(6):868-879. Published online March 23, 2021; DOI: https://doi.org/10.4093/dmj.2020.0149

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Background
Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients.
Methods
Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUC_gla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m² and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD.
Results
Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=–0.112 and r=0.157, respectively; P<0.001), and AUC_gla was also correlated with eGFR and UACR (r=–0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUC_gla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUC_gla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUC_gla were still independently associated with DKD.
Conclusion
Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.

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Glucagon in type 2 diabetes: Friend or foe?
Irene Caruso, Nicola Marrano, Giuseppina Biondi, Valentina Annamaria Genchi, Rossella D'Oria, Gian Pio Sorice, Sebastio Perrini, Angelo Cignarelli, Annalisa Natalicchio, Luigi Laviola, Francesco Giorgino
Diabetes/Metabolism Research and Reviews.2023;[Epub] CrossRef

Editorial

The Role of Carnitine Orotate Complex in Fatty Liver: Hyon-Seung Yi; Diabetes Metab J. 2021;45(6):866-867. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0272

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Reviews

Basic Research
Mitochondrial TFAM as a Signaling Regulator between Cellular Organelles: A Perspective on Metabolic Diseases: Jin-Ho Koh, Yong-Woon Kim, Dae-Yun Seo, Tae-Seo Sohn; Diabetes Metab J. 2021;45(6):853-865. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0138

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Tissues actively involved in energy metabolism are more likely to face metabolic challenges from bioenergetic substrates and are susceptible to mitochondrial dysfunction, leading to metabolic diseases. The mitochondria receive signals regarding the metabolic states in cells and transmit them to the nucleus or endoplasmic reticulum (ER) using calcium (Ca²⁺) for appropriate responses. Overflux of Ca²⁺ in the mitochondria or dysregulation of the signaling to the nucleus and ER could increase the incidence of metabolic diseases including insulin resistance and type 2 diabetes mellitus. Mitochondrial transcription factor A (Tfam) may regulate Ca²⁺ flux via changing the mitochondrial membrane potential and signals to other organelles such as the nucleus and ER. Since Tfam is involved in metabolic function in the mitochondria, here, we discuss the contribution of Tfam in coordinating mitochondria-ER activities for Ca²⁺ flux and describe the mechanisms by which Tfam affects mitochondrial Ca²⁺ flux in response to metabolic challenges.

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Basic Research
Brown Fat as a Regulator of Systemic Metabolism beyond Thermogenesis: Okamatsu-Ogura Yuko, Masayuki Saito; Diabetes Metab J. 2021;45(6):840-852. Published online June 25, 2021; DOI: https://doi.org/10.4093/dmj.2020.0291

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Brown adipose tissue (BAT) is a specialized tissue for nonshivering thermogenesis to dissipate energy as heat. Although BAT research has long been limited mostly in small rodents, the rediscovery of metabolically active BAT in adult humans has dramatically promoted the translational studies on BAT in health and diseases. Moreover, several remarkable advancements have been made in brown fat biology over the past decade: The molecular and functional analyses of inducible thermogenic adipocytes (socalled beige adipocytes) arising from a developmentally different lineage from classical brown adipocytes have been accelerated. In addition to a well-established thermogenic activity of uncoupling protein 1 (UCP1), several alternative thermogenic mechanisms have been discovered, particularly in beige adipocytes. It has become clear that BAT influences other peripheral tissues and controls their functions and systemic homeostasis of energy and metabolic substrates, suggesting BAT as a metabolic regulator, other than for thermogenesis. This notion is supported by discovering that various paracrine and endocrine factors are secreted from BAT. We review the current understanding of BAT pathophysiology, particularly focusing on its role as a metabolic regulator in small rodents and also in humans.

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Technology/Device
Current Advances of Artificial Pancreas Systems: A Comprehensive Review of the Clinical Evidence: Sun Joon Moon, Inha Jung, Cheol-Young Park; Diabetes Metab J. 2021;45(6):813-839. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0177

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Since Banting and Best isolated insulin in the 1920s, dramatic progress has been made in the treatment of type 1 diabetes mellitus (T1DM). However, dose titration and timely injection to maintain optimal glycemic control are often challenging for T1DM patients and their families because they require frequent blood glucose checks. In recent years, technological advances in insulin pumps and continuous glucose monitoring systems have created paradigm shifts in T1DM care that are being extended to develop artificial pancreas systems (APSs). Numerous studies that demonstrate the superiority of glycemic control offered by APSs over those offered by conventional treatment are still being published, and rapid commercialization and use in actual practice have already begun. Given this rapid development, keeping up with the latest knowledge in an organized way is confusing for both patients and medical staff. Herein, we explore the history, clinical evidence, and current state of APSs, focusing on various development groups and the commercialization status. We also discuss APS development in groups outside the usual T1DM patients and the administration of adjunct agents, such as amylin analogues, in APSs.

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Metabolic risk/Epidemiology
Obesity, Diabetes, and Increased Cancer Progression: Dae-Seok Kim, Philipp E. Scherer; Diabetes Metab J. 2021;45(6):799-812. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0077

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Rates of obesity and diabetes have increased significantly over the past decades and the prevalence is expected to continue to rise further in the coming years. Many observations suggest that obesity and diabetes are associated with an increased risk of developing several types of cancers, including liver, pancreatic, endometrial, colorectal, and post-menopausal breast cancer. The path towards developing obesity and diabetes is affected by multiple factors, including adipokines, inflammatory cytokines, growth hormones, insulin resistance, and hyperlipidemia. The metabolic abnormalities associated with changes in the levels of these factors in obesity and diabetes have the potential to significantly contribute to the development and progression of cancer through the regulation of distinct signaling pathways. Here, we highlight the cellular and molecular pathways that constitute the links between obesity, diabetes, cancer risk and mortality. This includes a description of the existing evidence supporting the obesity-driven morphological and functional alternations of cancer cells and adipocytes through complex interactions within the tumor microenvironment.

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