Diabetes & Metabolism Journal

Original Articles

Genetics
Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes: Siqian Gong, Hong Lian, Yating Li, Xiaoling Cai, Wei Liu, Yingying Luo, Meng Li, Si-min Zhang, Rui Zhang, Lingli Zhou, Yu Zhu, Qian Ren, Xiuying Zhang, Jing Chen, Jing Wu, Xianghai Zhou, Xirui Wang, Xueyao Han, Linong Ji; Received March 20, 2024 Accepted July 24, 2024 Published online November 13, 2024; DOI: https://doi.org/10.4093/dmj.2024.0159 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Others
Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea: Byung-Joon Kim, Jun-Seop Shin, Byoung-Hoon Min, Jong-Min Kim, Chung-Gyu Park, Hee-Jung Kang, Eung Soo Hwang, Won-Woo Lee, Jung-Sik Kim, Hyun Je Kim, Iov Kwon, Jae Sung Kim, Geun Soo Kim, Joonho Moon, Du Yeon Shin, Bumrae Cho, Heung-Mo Yang, Sung Joo Kim, Kwang-Won Kim; Diabetes Metab J. 2024;48(6):1160-1168. Published online May 21, 2024; DOI: https://doi.org/10.4093/dmj.2023.0260

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Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans.
Methods
A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness.
Conclusion
A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Complications
Glycemic Control and Retinal Microvascular Changes in Type 2 Diabetes Mellitus Patients without Clinical Retinopathy: Kangmin Lee, Ga Hye Lee, Seung Eun Lee, Jee Myung Yang, Kunho Bae; Diabetes Metab J. 2024;48(5):983-992. Published online March 13, 2024; DOI: https://doi.org/10.4093/dmj.2023.0149

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To investigate the association of glycemic control and retinal microvascular changes in patients with type 2 diabetes mellitus (T2DM) without diabetic retinopathy (DR).
Methods
This retrospective, observational, cohort study included patients with T2DM without DR. The patients were categorized into intensive control (IC; mean glycosylated hemoglobin [HbA1c] ≤7.0%) and moderate control (MC; mean HbA1c >7.0%) groups. Optical coherence tomography (OCT) and swept-source OCT angiography (OCTA) image parameters were compared between three groups, including healthy controls.
Results
In total, 259 eyes of 259 participants (88 IC, 81 MC, and 90 controls) were included. The foveal avascular zone area was significantly larger in the MC group than IC and control groups (all P<0.05). The IC group had lower vessel density in the superficial retinal layer and deep retinal layer than the controls (all P<0.05). The choriocapillaris (CC) flow deficit (FD) was significantly greater in the MC group than in the IC and control groups (18.2%, 16.7%, and 14.2%, respectively; all P<0.01). In multivariate regression analysis, CC-FD was associated with the mean HbA1c level (P=0.008). There were no significant differences in OCT parameters among the groups.
Conclusion
OCTA revealed that early CC impairment is associated with HbA1c levels; the CC changes precede clinically apparent DR. The OCTA parameters differed among the groups according to the degree of glycemic control. Our results suggest that microvascular changes precede DR and are closely related to glycemic control.

Lifestyle
Enhancing Diabetes Care through a Mobile Application: A Randomized Clinical Trial on Integrating Physical and Mental Health among Disadvantaged Individuals: Jae Hyun Bae, Eun Hee Park, Hae Kyung Lee, Kun Ho Yoon, Kyu Chang Won, Hyun Mi Kim, Sin Gon Kim; Diabetes Metab J. 2024;48(4):790-801. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0298

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This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership.
Methods
The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes selfmanagement through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16.
Results
Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups.
Conclusion
This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications.

Review

Pathophysiology
Epicardial Adipose Tissue and Heart Failure, Friend or Foe?: Dong-Hyuk Cho, Seong-Mi Park; Diabetes Metab J. 2024;48(3):373-384. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0190

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Heart failure (HF) management guidelines recommend individualized assessments based on HF phenotypes. Adiposity is a known risk factor for HF. Recently, there has been an increased interest in organ-specific adiposity, specifically the role of the epicardial adipose tissue (EAT), in HF risk. EAT is easily assessable through various imaging modalities and is anatomically and functionally connected to the myocardium. In pathological conditions, EAT secretes inflammatory cytokines, releases excessive fatty acids, and increases mechanical load on the myocardium, resulting in myocardial remodeling. EAT plays a pathophysiological role in characterizing both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). In HFrEF, EAT volume is reduced, reflecting an impaired metabolic reservoir, whereas in HFpEF, the amount of EAT is associated with worse biomarker and hemodynamic profiles, indicating increased EAT activity. Studies have examined the possibility of therapeutically targeting EAT, and recent studies using sodium glucose cotransporter 2 inhibitors have shown potential in reducing EAT volume. However, further research is required to determine the clinical implications of reducing EAT activity in patients with HF.

Citations

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New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review
Jorge E. Jalil, Luigi Gabrielli, María Paz Ocaranza, Paul MacNab, Rodrigo Fernández, Bruno Grassi, Paulina Jofré, Hugo Verdejo, Monica Acevedo, Samuel Cordova, Luis Sanhueza, Douglas Greig
International Journal of Molecular Sciences.2024; 25(8): 4407. CrossRef
Association of body adiposity with left ventricular concentric remodeling and diastolic dysfunction
In‐Jeong Cho, Sang‐Eun Lee, Wook Bum Pyun
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Original Article

Complications
Impact of Hyperglycemia on Complication and Mortality after Transarterial Chemoembolization for Hepatocellular Carcinoma: Sun Joon Moon, Chang Ho Ahn, Yun Bin Lee, Young Min Cho; Diabetes Metab J. 2024;48(2):302-311. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2022.0255

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Background
Current guidelines regarding periprocedural glycemic control to prevent complications after nonsurgical invasive procedures are insufficient. Transarterial chemoembolization (TACE) is a widely used treatment for unresectable hepatocellular carcinoma. We aimed to investigate the association between diabetes mellitus (DM) per se and the degree of hyperglycemia with postprocedural complications after TACE.
Methods
A total of 22,159 TACE procedures performed at Seoul National University Hospital from 2005 to 2018 were retrospectively analyzed. The associations between DM, preprocedural glycosylated hemoglobin (HbA1c), and periprocedural average glucose with postprocedural adverse outcomes were evaluated. The primary outcome was occurrence of postprocedural bacteremia. Secondary outcomes were acute kidney injury (AKI), delayed discharge and death within 14 days. Periprocedural glucose was averaged over 3 days: the day of, before, and after the TACE procedures. Propensity score matching was applied for procedures between patients with or without DM.
Results
Periprocedural average glucose was significantly associated with bacteremia (adjusted odds ratio per 50 mg/dL of glucose, 1.233; 95% confidence interval, 1.071 to 1.420; P=0.004), AKI, delayed discharge, and death within 14 days. DM per se was only associated with bacteremia and AKI. Preprocedural HbA1c was associated with delayed discharge. Average glucose levels above 202 and 181 mg/dL were associated with a significantly higher risk of bacteremia and AKI, respectively, than glucose levels of 126 mg/dL or lower.
Conclusion
Periprocedural average glucose, but not HbA1c, was associated with adverse outcomes after TACE, which is a nonsurgical invasive procedure. This suggests the importance of periprocedural glycemic control to reduce postprocedural complications.

Citations

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Serum CYFRA 21-1 and CK19-2G2 as Predictive Biomarkers of Response to Transarterial Chemoembolization in Hepatitis C–related Hepatocellular Carcinoma Among Egyptians: A Prospective Study
Mohamed Y. Taher, Ehab Hassouna, Abeer El Hadidi, Omar El-aassar, Mohamed Fathy Bakosh, Mohamed Said Shater
Journal of Clinical and Experimental Hepatology.2025; 15(1): 102405. CrossRef

Review

Cardiovascular Risk/Epidemiology
Intensified Multifactorial Intervention in Patients with Type 2 Diabetes Mellitus: Takayoshi Sasako, Toshimasa Yamauchi, Kohjiro Ueki; Diabetes Metab J. 2023;47(2):185-197. Published online January 12, 2023; DOI: https://doi.org/10.4093/dmj.2022.0325

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In the management of diabetes mellitus, one of the most important goals is to prevent its micro- and macrovascular complications, and to that end, multifactorial intervention is widely recommended. Intensified multifactorial intervention with pharmacotherapy for associated risk factors, alongside lifestyle modification, was first shown to be efficacious in patients with microalbuminuria (Steno-2 study), then in those with less advanced microvascular complications (the Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care [ADDITION]-Europe and the Japan Diabetes Optimal Treatment study for 3 major risk factors of cardiovascular diseases [J-DOIT3]), and in those with advanced microvascular complications (the Nephropathy In Diabetes-Type 2 [NID-2] study and Diabetic Nephropathy Remission and Regression Team Trial in Japan [DNETT-Japan]). Thus far, multifactorial intervention led to a reduction in cardiovascular and renal events, albeit not necessarily significant. It should be noted that not only baseline characteristics but also the control status of the risk factors and event rates during intervention among the patients widely varied from one trial to the next. Further evidence is needed for the efficacy of multifactorial intervention in a longer duration and in younger or elderly patients. Moreover, now that new classes of antidiabetic drugs are available, it should be addressed whether strict and safe glycemic control, alongside control of other risk factors, could lead to further risk reductions in micro- and macrovascular complications, thereby decreasing all-cause mortality in patients with type 2 diabetes mellitus.

Citations

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Exploring mechanisms underlying diabetes comorbidities and strategies to prevent vascular complications
Takayoshi Sasako
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Targeting ERS-mitophagy in hippocampal neurons to explore the improvement of memory by tea polyphenols in aged type 2 diabetic rats
Wenjuan Feng, Chenhui Lv, Le Cheng, Xin Song, Xuemin Li, Haoran Xie, Shuangzhi Chen, Xi Wang, Lushan Xue, Cheng Zhang, Jie Kou, Lili Wang, Haifeng Zhao
Free Radical Biology and Medicine.2024; 213: 293. CrossRef
Risk of Dementia Among Patients With Diabetes in a Multidisciplinary, Primary Care Management Program
Kailu Wang, Shi Zhao, Eric Kam-Pui Lee, Susan Zi-May Yau, Yushan Wu, Chi-Tim Hung, Eng-Kiong Yeoh
JAMA Network Open.2024; 7(2): e2355733. CrossRef
Causes of In-Hospital Death and Pharmaceutical Associations with Age of Death during a 10-Year Period (2011–2020) in Individuals with and without Diabetes at a Japanese Community General Hospital
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External validation of a minimal-resource model to predict reduced estimated glomerular filtration rate in people with type 2 diabetes without diagnosis of chronic kidney disease in Mexico: a comparison between country-level and regional performance
Camilla Sammut-Powell, Rose Sisk, Ruben Silva-Tinoco, Gustavo de la Pena, Paloma Almeda-Valdes, Sonia Citlali Juarez Comboni, Susana Goncalves, Rory Cameron
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Original Articles

Complication
Waist Circumference and Body Mass Index Variability and Incident Diabetic Microvascular Complications: A Post Hoc Analysis of ACCORD Trial: Daniel Nyarko Hukportie, Fu-Rong Li, Rui Zhou, Jia-Zhen Zheng, Xiao-Xiang Wu, Xian-Bo Wu; Diabetes Metab J. 2022;46(5):767-780. Published online May 10, 2022; DOI: https://doi.org/10.4093/dmj.2021.0258

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Background
Obesity is associated with adverse health events among diabetic patients, however, the relationship between obesity fluctuation and risk of microvascular complications among this specific population is unclear. We aimed to examine the effect of waist circumference (WC) and body mass index (BMI) variability on the risk of diabetic microvascular outcome
Methods
Annually recorded anthropometric data in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study was used to examine the association of WC and BMI variability defined as variability independent of mean, with the risk of microvascular outcomes, including neuropathy, nephropathy, and retinopathy. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) (Trial registration: ClinicalTrials.gov., no. NCT00000620).
Results
There were 4,031, 5,369, and 2,601 cases of neuropathy, nephropathy, and retinopathy during a follow-up period of 22,524, 23,941, and 23,850 person-years, respectively. Higher levels of WC and BMI variability were associated with an increased risk of neuropathy. Compared with the lowest quartile, the fully-adjusted HR (95% CI) for the highest quartile of WC and BMI variability for neuropathy risk were 1.21 (1.05 to 1.40) and 1.16 (1.00 to 1.33), respectively. Also, higher quartiles of BMI variability but not WC variability were associated with increased risk of nephropathic events. The fully-adjusted HR (95% CI) for the highest quartile compared with the lowest quartile of BMI variability was 1.31 (1.18 to 1.46). However, the results for retinopathic events were all insignificant.
Conclusion
Among participants with type 2 diabetes mellitus, WC and BMI variability were associated with a higher risk of neuropathic events, whereas BMI variability was associated with an increased risk of nephropathic events.

Citations

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Association of body mass index and blood pressure variability with 10-year mortality and renal disease progression in type 2 diabetes
Stephen Fava, Sascha Reiff
Acta Diabetologica.2024; 61(6): 747. CrossRef
Investigating the causal association of generalized and abdominal obesity with microvascular complications in patients with type 2 diabetes: A community‐based prospective study
Jiaheng Chen, Yu Ting Li, Zimin Niu, Zhanpeng He, Yao Jie Xie, Jose Hernandez, Wenyong Huang, Harry H X Wang
Diabetes, Obesity and Metabolism.2024; 26(7): 2796. CrossRef
Serum Spexin Level Is Negatively Associated With Peripheral Neuropathy and Sensory Pain in Type 2 Diabetes
Ying Liu, Di Wu, Hangping Zheng, Yunzhi Ni, Lu Zhu, Yaojing Jiang, Jiarong Dai, Quanya Sun, Ying Zhao, Qi Zhang, Yehong Yang, Rui Liu, Vincenza Spallone
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Cardiovascular health metrics and diabetic nephropathy: a nationally representative cross-sectional study
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Association between body fat variation rate and risk of diabetic nephropathy - a posthoc analysis based on ACCORD database
Shuai Li, Li Lin, Xiaoyue Chen, Siyu Liu, Ming Gao, Xunjie Cheng, Chuanchang Li
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Association of variabilities in body mass index and metabolic parameters with post-kidney transplantation renal outcomes
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Waist Circumference and Body Mass Index Variability and Incident Diabetic Microvascular Complications: A Post Hoc Analysis of ACCORD Trial (Diabetes Metab J 2022;46:767-80)
Yun Kyung Cho
Diabetes & Metabolism Journal.2023; 47(1): 147. CrossRef
Waist Circumference and Body Mass Index Variability and Incident Diabetic Microvascular Complications: A Post Hoc Analysis of ACCORD Trial (Diabetes Metab J 2022;46:767-80)
Daniel Nyarko Hukportie, Fu-Rong Li, Rui Zhou, Jia-Zhen Zheng, Xiao-Xiang Wu, Xian-Bo Wu
Diabetes & Metabolism Journal.2023; 47(1): 150. CrossRef
Weight variability and diabetes complications
Francesco Prattichizzo, Chiara Frigé, Rosalba La Grotta, Antonio Ceriello
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Oscar Vivanco-Rojas, Sonia López-Letayf, Valentina Londoño-Angarita, Fátima Sofía Magaña-Guerrero, Beatriz Buentello-Volante, Yonathan Garfias
Journal of Clinical Medicine.2023; 12(20): 6583. CrossRef
Effects of body weight variability on risks of macro- and microvascular outcomes in individuals with type 2 diabetes: The Rio de Janeiro type 2 diabetes cohort
Claudia R.L. Cardoso, Nathalie C. Leite, Gil F. Salles
Diabetes Research and Clinical Practice.2023; 205: 110992. CrossRef
Correlation Between the Variability of Different Obesity Indices and Diabetic Kidney Disease: A Retrospective Cohort Study Based on Populations in Taiwan
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Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 2791. CrossRef
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Kangli Yin, Tianci Qiao, Yongkang Zhang, Jiarui Liu, Yuzhen Wang, Fei Qi, Junlin Deng, Cheng Zhao, Yongcheng Xu, Yemin Cao
BMJ Open Diabetes Research & Care.2023; 11(6): e003523. CrossRef

Metabolic Risk/Epidemiology
Effect of Different Types of Diagnostic Criteria for Gestational Diabetes Mellitus on Adverse Neonatal Outcomes: A Systematic Review, Meta-Analysis, and Meta-Regression: Fahimeh Ramezani Tehrani, Marzieh Saei Ghare Naz, Razieh Bidhendi-Yarandi, Samira Behboudi-Gandevani; Diabetes Metab J. 2022;46(4):605-619. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0178

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Background
Evidence supporting various diagnostic criteria for diagnose gestational diabetes mellitus (GDM) are consensus-based, needs for additional evidence related to outcomes. Therefore, the aim of this systematic-review and meta-analysis was to assess the impact of different GDM diagnostic-criteria on the risk of adverse-neonatal-outcomes.
Methods
Electronic databases including Scopus, PubMed, and Web of Sciences were searched to retrieve English original, population-based studies with the universal GDM screening approach, up to January-2020. GDM diagnostic criteria were classified in seven groups and International Association of the Diabetes and Pregnancy Study Groups (IADPSG) was considered as reference one. We used the Mantel–Haenszel method to calculate the pooled odds of events. The possibility of publication bias was examined by Begg’s test.
Results
A total of 55 population-based studies consisting of 1,604,391 pregnant women with GDM and 7,770,855 non-GDM counterparts were included. Results showed that in all diagnostic-criteria subgroups, the risk of adverse neonatal outcomes including macrosomia, hyperbilirubinemia, respiratory distress syndrome, neonatal hypoglycemia, neonatal intensive care unit admission, preterm birth, and birth-trauma were significantly higher than the non-GDM counterparts were significantly higher than non-GDM counterparts. Meta-regression analysis revealed that the magnitude of neonatal risks in all diagnostic-criteria subgroups are similar.
Conclusion
Our results showed that the risk of adverse-neonatal-outcome increased among women with GDM, but the magnitude of risk was not different among those women who were diagnosed through more or less intensive strategies. These findings may help health-care-providers and policy-makers to select the most cost-effective approach for the screening of GDM among pregnant women.

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Blood Cells Parameters in Second Trimester of Pregnancy and Gestational Diabetes Mellitus: A Systematic Review and Meta‐Analysis
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One-step vs 2-step gestational diabetes mellitus screening and pregnancy outcomes: an updated systematic review and meta-analysis
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Cardiovascular risk factors in Moroccan women: systematic review and meta-analysis
Es-sabir Fatima, Lahlou Laila, Afaf Bouqoufi, Lahoucine Amsdar, Majdouline Obtel
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Short Communication

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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Original Articles

Lifestyle
Changes in Patterns of Physical Activity and Risk of Heart Failure in Newly Diagnosed Diabetes Mellitus Patients: Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Eun-Jung Rhee, Won-Young Lee; Diabetes Metab J. 2022;46(2):327-336. Published online November 24, 2021; DOI: https://doi.org/10.4093/dmj.2021.0046

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Background
Exercise is recommended for type 2 diabetes mellitus (T2DM) patients to prevent cardiovascular disease. However, the effects of physical activity (PA) for reducing the risk of heart failure (HF) has yet to be elucidated. We aimed to assess the effect of changes in patterns of PA on incident HF, especially in newly diagnosed diabetic patients.
Methods
We examined health examination data and claims records of 294,528 participants from the Korean National Health Insurance Service who underwent health examinations between 2009 and 2012 and were newly diagnosed with T2DM. Participants were classified into the four groups according to changes in PA between before and after the diagnosis of T2DM: continuously inactive, inactive to active, active to inactive, and continuously active. The development of HF was analyzed until 2017.
Results
As compared with those who were continuously inactive, those who became physically active after diagnosis showed a reduced risk for HF (adjusted hazard ratio [aHR], 0.79; 95% confidence interval [CI], 0.66 to 0.93). Those who were continuously active had the lowest risk for HF (aHR, 0.77; 95% CI, 0.62 to 0.96). As compared with those who were inactive, those who exercised regularly, either performing vigorous or moderate PA, had a lower HF risk (aHR, 0.79; 95% CI, 0.69 to 0.91).
Conclusion
Among individuals with newly diagnosed T2DM, the risk of HF was reduced in those with higher levels of PA after diagnosis was made. Our results suggest either increasing or maintaining the frequency of PA after the diagnosis of T2DM may lower the risk of HF.

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The Journal of Clinical Endocrinology & Metabolism.2024; 109(3): e1194. CrossRef
Association between exercise habits and incident type 2 diabetes mellitus in patients with thyroid cancer: nationwide population-based study
Jiyun Park, Jin-Hyung Jung, Hyunju Park, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyungdo Han, Kyung-Soo Kim
BMC Medicine.2024;[Epub] CrossRef
Dose-Response Relationship Between Physical Activity and the Morbidity and Mortality of Cardiovascular Disease Among Individuals With Diabetes: Meta-Analysis of Prospective Cohort Studies
Yang Chen, Xingsheng Jin, Guochong Chen, Ru Wang, Haili Tian
JMIR Public Health and Surveillance.2024; 10: e54318. CrossRef
Life-course obesity and heart failure: a two-sample Mendelian randomization study
Haili Wang, Jie Min, Lei Zhong, Jinyu Zhang, Lili Ye, Chunrong Chen
Internal and Emergency Medicine.2024;[Epub] CrossRef
Evaluation and Management of Patients With Diabetes and Heart Failure: A Korean Diabetes Association and Korean Society of Heart Failure Consensus Statement
Kyu-Sun Lee, Junghyun Noh, Seong-Mi Park, Kyung Mook Choi, Seok-Min Kang, Kyu-Chang Won, Hyun-Jai Cho, Min Kyong Moon
International Journal of Heart Failure.2023; 5(1): 1. CrossRef
Evaluation and Management of Patients with Diabetes and Heart Failure: A Korean Diabetes Association and Korean Society of Heart Failure Consensus Statement
Kyu-Sun Lee, Junghyun Noh, Seong-Mi Park, Kyung Mook Choi, Seok-Min Kang, Kyu-Chang Won, Hyun-Jai Cho, Min Kyong Moon
Diabetes & Metabolism Journal.2023; 47(1): 10. CrossRef
Association of plasma brain-derived neurotrophic factor levels and frailty in community-dwelling older adults
Eun Roh, Soon Young Hwang, Eyun Song, Min Jeong Park, Hye Jin Yoo, Sei Hyun Baik, Miji Kim, Chang Won Won, Kyung Mook Choi
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COVID-19
Effects of Social Distancing on Diabetes Management in Older Adults during COVID-19 Pandemic: Soo Myoung Shin, Tae Jung Oh, Sung Hee Choi, Hak Chul Jang; Diabetes Metab J. 2021;45(5):765-772. Published online August 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0096

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Background
On March 22, 2020, intense social distancing (SD) was implemented in Korea to prevent the spread of coronavirus disease 19 (COVID-19). This study examined the impact of SD on diabetes control in older adults with diabetes.
Methods
Adults aged 60 to 90 years with type 2 diabetes mellitus who were physically and mentally independent were recruited. Participants who had complete blood chemistry data from April to July 2019 (pre-SD era) and April to July 2020 (SD era) were enrolled. Data were obtained about physical activity, nutrition, sarcopenia, and psychological and mental health from questionnaires in April to July 2020. Calf circumference was measured.
Results
In total, 246 people (100 men, 146 women; mean age, 73.8±5.7 years) participated in this study. The levels of glycated hemoglobin (HbA1c, 7.4%±1.0% vs. 7.1%±0.8%, P<0.001), fasting glucose (142.2±16.7 mg/dL vs. 132.0±27.7 mg/dL, P<0.001), and body weight (62.6±9.4 kg vs. 61.8±10.1 kg, P<0.01) were higher in the SD era than in the pre-SD era. Total physical activity was lower in the SD era (2,584.6±2,624.1 MET-min/week^–1 vs. 1,987.3±2,295.0 MET-min/week^–1, P<0.001). A larger increase in HbA1c level was associated with increased body weight and decreased physical activity.
Conclusion
SD had negative effects on diabetes management in older adults with diabetes. Fasting glucose and HbA1c levels and body weight increased during the SD era. Participants with reduced physical activity gained more weight and had higher blood glucose levels. Given that the COVID-19 pandemic is ongoing, health professionals and diabetes educators should monitor changes in lifestyle factors in older adults with diabetes.

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Kirrilee Jane Barlow, Paul P Fahey, Evan Atlantis
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Drug/Regimen
Efficacy and Safety of Self-Titration Algorithms of Insulin Glargine 300 units/mL in Individuals with Uncontrolled Type 2 Diabetes Mellitus (The Korean TITRATION Study): A Randomized Controlled Trial: Jae Hyun Bae, Chang Ho Ahn, Ye Seul Yang, Sun Joon Moon, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho; Diabetes Metab J. 2022;46(1):71-80. Published online June 16, 2021; DOI: https://doi.org/10.4093/dmj.2020.0274

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Background
To compare the efficacy and safety of two insulin self-titration algorithms, Implementing New Strategies with Insulin Glargine for Hyperglycemia Treatment (INSIGHT) and EDITION, for insulin glargine 300 units/mL (Gla-300) in Korean individuals with uncontrolled type 2 diabetes mellitus (T2DM).
Methods
In a 12-week, randomized, open-label trial, individuals with uncontrolled T2DM requiring basal insulin were randomized to either the INSIGHT (adjusted by 1 unit/day) or EDITION (adjusted by 3 units/week) algorithm to achieve a fasting self-monitoring of blood glucose (SMBG) in the range of 4.4 to 5.6 mmol/L. The primary outcome was the proportion of individuals achieving a fasting SMBG ≤5.6 mmol/L without noct urnal hypoglycemia at week 12.
Results
Of 129 individuals (age, 64.1±9.5 years; 66 [51.2%] women), 65 and 64 were randomized to the INSIGHT and EDITION algorithms, respectively. The primary outcome of achievement was comparable between the two groups (24.6% vs. 23.4%, P=0.876). Compared with the EDITION group, the INSIGHT group had a greater reduction in 7-point SMBG but a similar decrease in fasting plasma glucose and glycosylated hemoglobin. The increment of total daily insulin dose was significantly higher in the INSIGHT group than in the EDITION group (between-group difference: 5.8±2.7 units/day, P=0.033). However, body weight was significantly increased only in the EDITION group (0.6±2.4 kg, P=0.038). There was no difference in the occurrence of hypoglycemia between the two groups. Patient satisfaction was significantly increased in the INSIGHT group (P=0.014).
Conclusion
The self-titration of Gla-300 using the INSIGHT algorithm was effective and safe compared with that using the EDITION algorithm in Korean individuals with uncontrolled T2DM (ClinicalTrials.gov number: NCT03406663).

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Time for Using Machine Learning for Dose Guidance in Titration of People With Type 2 Diabetes? A Systematic Review of Basal Insulin Dose Guidance
Camilla Heisel Nyholm Thomsen, Stine Hangaard, Thomas Kronborg, Peter Vestergaard, Ole Hejlesen, Morten Hasselstrøm Jensen
Journal of Diabetes Science and Technology.2024; 18(5): 1185. CrossRef
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Hazem Ayesh, Sajida Suhail, Suhail Ayesh, Kevin Niswender
Diabetes, Obesity and Metabolism.2024; 26(9): 3801. CrossRef
Basal insulin titration algorithms in patients with type 2 diabetes: the simplest is the best (?)
V.I. Katerenchuk
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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.

Review

Type 1 Diabetes
Time in Range from Continuous Glucose Monitoring: A Novel Metric for Glycemic Control: Jee Hee Yoo, Jae Hyeon Kim; Diabetes Metab J. 2020;44(6):828-839. Published online December 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0257; Correction in: Diabetes Metab J 2021;45(5):795

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Glycosylated hemoglobin (HbA1c) has been the sole surrogate marker for assessing diabetic complications. However, consistently reported limitations of HbA1c are that it lacks detailed information on short-term glycemic control and can be easily interfered with by various clinical conditions such as anemia, pregnancy, or liver disease. Thus, HbA1c alone may not represent the real glycemic status of a patient. The advancement of continuous glucose monitoring (CGM) has enabled both patients and healthcare providers to monitor glucose trends for a whole single day, which is not possible with HbA1c. This has allowed for the development of core metrics such as time spent in time in range (TIR), hyperglycemia, or hypoglycemia, and glycemic variability. Among the 10 core metrics, TIR is reported to represent overall glycemic control better than HbA1c alone. Moreover, various evidence supports TIR as a predictive marker of diabetes complications as well as HbA1c, as the inverse relationship between HbA1c and TIR reveals. However, there are more complex relationships between HbA1c, TIR, and other CGM metrics. This article provides information about 10 core metrics with particular focus on TIR and the relationships between the CGM metrics for comprehensive understanding of glycemic status using CGM.

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Advanced Sensor Research.2024;[Epub] CrossRef
Association between glucose levels of children with type 1 diabetes and parental economic status in mobile health application
Wen-Hao Zhang, Chao-Fan Wang, Hao Wang, Jie Tang, Hong-Qiang Zhang, Jiang-Yu Zhu, Xue-Ying Zheng, Si-Hui Luo, Yu Ding
World Journal of Diabetes.2024; 15(7): 1477. CrossRef
Differences Between Glycated Hemoglobin and Glucose Management Indicator in Real-Time and Intermittent Scanning Continuous Glucose Monitoring in Adults With Type 1 Diabetes
Jee Hee Yoo, Sun Joon Moon, Cheol-Young Park, Jae Hyeon Kim
Journal of Diabetes Science and Technology.2024;[Epub] CrossRef
Impact of diverse aerobic exercise plans on glycemic control, lipid levels, and functional activity in stroke patients with type 2 diabetes mellitus
Kangcheng Chen, Yulong Wang, Dongxia Li, Jun Li, Yong Huang, Meiling Huang, Haifeng Ma
Frontiers in Endocrinology.2024;[Epub] CrossRef
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Lehel Dénes-Fazakas, László Szilágyi, Levente Kovács, Andrea De Gaetano, György Eigner
Biomedicines.2024; 12(9): 2143. CrossRef
A Review of Third-Trimester Complications in Pregnancies Complicated by Diabetes Mellitus
Shaun R. Welsey, Jessica Day, Scott Sullivan, Sarah D. Crimmins
American Journal of Perinatology.2024;[Epub] CrossRef
Anagliptin twice‐daily regimen improves glycaemic variability in subjects with type 2 diabetes: A double‐blind, randomized controlled trial
Yong‐ho Lee, Doo‐Man Kim, Jae Myung Yu, Kyung Mook Choi, Sin Gon Kim, Kang Seo Park, Hyun‐Shik Son, Choon Hee Chung, Kyu Jeung Ahn, Soon Hee Lee, Ki‐Ho Song, Su Kyoung Kwon, Hyeong Kyu Park, Kyu Chang Won, Hak Chul Jang
Diabetes, Obesity and Metabolism.2023; 25(5): 1174. CrossRef
Advances in Continuous Glucose Monitoring and Integrated Devices for Management of Diabetes with Insulin-Based Therapy: Improvement in Glycemic Control
Jee Hee Yoo, Jae Hyeon Kim
Diabetes & Metabolism Journal.2023; 47(1): 27. CrossRef
Status of continuous glucose monitoring use and management in tertiary hospitals of China: a cross-sectional study
Liping Chen, Xiaoqin Liu, Qin Lin, Hongmei Dai, Yong Zhao, Zumin Shi, Liping Wu
BMJ Open.2023; 13(2): e066801. CrossRef
Real-world outcomes of continuous glucose monitoring in adults with diabetes mellitus attending an Irish tertiary hospital
Aoife Courtney, Diarmuid Smith, Hannah Forde
Irish Journal of Medical Science (1971 -).2023; 192(6): 2763. CrossRef
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Microchimica Acta.2023;[Epub] CrossRef
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Shuo Zhang, Chuanyan Zhang, Jingxian Chen, Feiying Deng, Zezhen Wu, Dan Zhu, Fengwu Chen, Yale Duan, Yue Zhao, Kaijian Hou
Frontiers in Pharmacology.2023;[Epub] CrossRef
Impact of continuous glucose monitoring on glycemic control and its derived metrics in type 1 diabetes: a longitudinal study
So Hyun Cho, Seohyun Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim
Frontiers in Endocrinology.2023;[Epub] CrossRef
Association Between Continuous Glucose Monitoring-Derived Glycemia Risk Index and Albuminuria in Type 2 Diabetes
Jee Hee Yoo, Ji Yoon Kim, Jae Hyeon Kim
Diabetes Technology & Therapeutics.2023; 25(10): 726. CrossRef
Acute Glycemic Variability and Early Outcomes After Cardiac Surgery: A Meta-Analysis
Shuo Chang, Mian Xu, Yu Wang, Yanbo Zhang
Hormone and Metabolic Research.2023; 55(11): 771. CrossRef
Comparison of Glycemia Risk Index with Time in Range for Assessing Glycemic Quality
Ji Yoon Kim, Jee Hee Yoo, Jae Hyeon Kim
Diabetes Technology & Therapeutics.2023; 25(12): 883. CrossRef
Correlação entre tempo no alvo e hemoglobina glicada de pessoas com diabetes mellitus: revisão sistemática
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Revista Latino-Americana de Enfermagem.2023;[Epub] CrossRef
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Revista Latino-Americana de Enfermagem.2023;[Epub] CrossRef
Smart Insulin Pen: Managing Insulin Therapy for People with Diabetes in the Digital Era
Jee Hee Yoo, Jae Hyeon Kim
The Journal of Korean Diabetes.2023; 24(4): 190. CrossRef
Novel Glycemic Index Based on Continuous Glucose Monitoring to Predict Poor Clinical Outcomes in Critically Ill Patients: A Pilot Study
Eun Yeong Ha, Seung Min Chung, Il Rae Park, Yin Young Lee, Eun Young Choi, Jun Sung Moon
Frontiers in Endocrinology.2022;[Epub] CrossRef
Hypoglycemic agents and glycemic variability in individuals with type 2 diabetes: A systematic review and network meta-analysis
SuA Oh, Sujata Purja, Hocheol Shin, Minji Kim, Eunyoung Kim
Diabetes and Vascular Disease Research.2022;[Epub] CrossRef
Advanced Glycation End Products and Their Effect on Vascular Complications in Type 2 Diabetes Mellitus
Jeongmin Lee, Jae-Seung Yun, Seung-Hyun Ko
Nutrients.2022; 14(15): 3086. CrossRef
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Frontiers in Endocrinology.2022;[Epub] CrossRef
Glucose Profiles Assessed by Intermittently Scanned Continuous Glucose Monitoring System during the Perioperative Period of Metabolic Surgery
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Diabetes & Metabolism Journal.2022; 46(5): 713. CrossRef
Deterioration in glycemic control on schooldays among children and adolescents with type 1 diabetes: A continuous glucose monitoring-based study
Yu Ding, Wenhao Zhang, Xiumei Wu, Tian Wei, Xulin Wang, Xueying Zheng, Sihui Luo
Frontiers in Pediatrics.2022;[Epub] CrossRef
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Roland Feldbauer, Matthias Wolfgang Heinzl, Carmen Klammer, Michael Resl, Johannes Pohlhammer, Klemens Rosenberger, Verena Almesberger, Florian Obendorf, Lukas Schinagl, Thomas Wagner, Margot Egger, Benjamin Dieplinger, Martin Clodi, Stephen L. Atkin
PLOS ONE.2022; 17(12): e0279308. CrossRef
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Akemi Tokutsu, Yosuke Okada, Keiichi Torimoto, Yoshiya Tanaka
Diabetology & Metabolic Syndrome.2021;[Epub] CrossRef
Time-in-range for monitoring glucose control: Is it time for a change?
Virginia Bellido, Pedro José Pinés-Corrales, Rocío Villar-Taibo, Francisco Javier Ampudia-Blasco
Diabetes Research and Clinical Practice.2021; 177: 108917. CrossRef
Glucose Management Indicator for People with Type 1 Asian Diabetes Is Different from That of the Published Equation: Differences by Glycated Hemoglobin Distribution
Jee Hee Yoo, Seung Hee Yang, Gyuri Kim, Jae Hyeon Kim
Diabetes Technology & Therapeutics.2021;[Epub] CrossRef
Health-Related Quality of Life, Family Conflicts and Fear of Injecting: Perception Differences between Preadolescents and Adolescents with Type 1 Diabetes and Their Mothers
Marta Tremolada, Maria Cusinato, Sabrina Bonichini, Arianna Fabris, Claudia Gabrielli, Carlo Moretti
Behavioral Sciences.2021; 11(7): 98. CrossRef
Daytime Glycemic Variability and Frailty in Older Patients with Diabetes: a Pilot Study Using Continuous Glucose Monitoring
Seung Min Chung, Yun Hee Lee, Chang Oh Kim, Ji Yeon Lee, Sang-Man Jin, Seung-Hyun Yoo, Jun Sung Moon, Kwang Joon Kim
Journal of Korean Medical Science.2021;[Epub] CrossRef
Benefits of a Switch from Intermittently Scanned Continuous Glucose Monitoring (isCGM) to Real-Time (rt) CGM in Diabetes Type 1 Suboptimal Controlled Patients in Real-Life: A One-Year Prospective Study §
Yannis Préau, Sébastien Galie, Pauline Schaepelynck, Martine Armand, Denis Raccah
Sensors.2021; 21(18): 6131. CrossRef
Recent Advances of Integrative Bio-Omics Technologies to Improve Type 1 Diabetes (T1D) Care
Nisha Karwal, Megan Rodrigues, David D. Williams, Ryan J. McDonough, Diana Ferro
Applied Sciences.2021; 11(24): 11602. CrossRef

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