Diabetes & Metabolism Journal

Review

Others
Differences between Type 2 Diabetes Mellitus and Obesity Management: Medical, Social, and Public Health Perspectives: Soo Lim, Ga Eun Nam, Arya M. Sharma; Received April 2, 2025 Accepted May 6, 2025 Published online June 11, 2025; DOI: https://doi.org/10.4093/dmj.2025.0278 [Epub ahead of print]

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Abstract PDF PubReader ePub: Obesity and type 2 diabetes mellitus (T2DM) are among the most urgent global public health challenges, yet differ markedly in recognition and management across medical, social, infrastructure, and policy domains. T2DM is supported by clear diagnostic criteria, defined treatment targets, and broad acceptance as a chronic disease. In contrast, obesity is assessed using imprecise metrics like body mass index, lacks standardized treatment goals, and is often misunderstood as a lifestyle issue rather than a chronic, relapsing disease. This misconception contributes to stigma, discrimination, and unrealistic patient expectations. T2DM receives substantial research funding, comprehensive clinical guidelines, and structured medical education, with strong support from large professional societies and multidisciplinary care models. Obesity care remains underfunded, inconsistently delivered, and underrepresented in medical training. Public health and policy efforts strongly favor T2DM, providing coordinated programs, insurance coverage, and regulatory oversight. Conversely, obesity is marginalized, with limited policy influence and a largely unregulated commercial weight-loss industry. Bridging these disparities requires adopting lessons from T2DM management—such as evidence-based guidelines, improved provider training, expanded insurance coverage, and public health strategies—to enhance obesity care and recognize it as a chronic disease requiring long-term, structured management.

Original Articles

Metabolic Rrisk/Epidemiology
Birth Weight, Cardiovascular Health, and Microvascular Complications in Individuals with Diabetes Mellitus: Chaolun Yu, Anping Feng, Xia Zou, Siqi Chen, Lingyan Dai, Qingmei Cui, Xiaojing Kuang, Gaoli She, Ying Ma, Haixia Guan, Jie Li; Received August 29, 2024 Accepted December 30, 2024 Published online May 23, 2025; DOI: https://doi.org/10.4093/dmj.2024.0518 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Diabetes often leads to microvascular complications, including nephropathy, neuropathy, and retinopathy. Understanding the impact of early-life factors like birth weight and modifiable behaviors such as cardiovascular health (CVH) is essential for preventing these complications.
Methods
We included 11,515 participants with diabetes but without microvascular complications at baseline from the UK Biobank Study. CVH was evaluated using the Life’s Essential 8 score. Independent and joint associations of birth weight and CVH with microvascular complications were analyzed using Cox proportional hazard models. Two-sample Mendelian randomization (MR) analyses estimated unconfounded associations between birth weight and microvascular complications.
Results
Over a median follow-up of 13.1 years, 3,010 microvascular complications occurred. Compared with normal birth weight (2.5–4.0 kg), low birth weight (LBW; <2.5 kg) was associated with 15% higher risk of diabetic nephropathy (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.01 to 1.31), but not with neuropathy and retinopathy. High birth weight (>4.0 kg) was not associated with the risk of diabetic microvascular complications. MR analysis confirmed the association between LBW and nephropathy. Adherence to high CVH was associated with a reduced risk of microvascular complications compared to low CVH, regardless of birth weight. The HRs were 0.70 (95% CI, 0.59 to 0.84) for the LBW group and 0.74 (95% CI, 0.68 to 0.80) for the group with birth weight ≥2.5 kg (P for interaction=0.69).
Conclusion
LBW was an independent risk factor for nephropathy among diabetic patients. However, the detrimental effects of LBW might be mitigated by improvement in CVH.

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; Diabetes Metab J. 2025;49(2):321-330. Published online November 13, 2024; DOI: https://doi.org/10.4093/dmj.2024.0159

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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.

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Diabetes associated with HNF1B: beyond Occam’s razor—A case report
Carolina Sager-La Ganga, Clara Solà, Karen Castillo, Carme Figueredo, Ignacio Conget
Acta Diabetologica.2025;[Epub] CrossRef

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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Background
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.

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Allogeneic Islet Transplantation: Chronicle of a Death Foretold?
Thierry Berney, Olivier Thaunat, Ekaterine Berishvili
Transplant International.2025;[Epub] CrossRef
Donor pigs for clinical islet xenotransplantation: Review and future directions
Shinichi Matsumoto, Sadaki Asari, Yoshihide Nanno, Hiroyuki Nakamura, Taisuke Okawa, Takumi Fukumoto
Cell Transplantation.2025;[Epub] CrossRef

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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Background
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.

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Flow and ischemic changes in retina and choroid across diabetic retinopathy spectrum: a SS-OCTA study
Qianhui Yang, Kelvin Y. C. Teo, Yueheng Hong, Bingyao Tan, Leopold Schmetterer, Chui Ming Gemmy Cheung, Tien Yin Wong, Gavin Tan Siew Wei
Eye.2025; 39(8): 1631. CrossRef

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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Background
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.

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Social determinants of health and type 2 diabetes in Asia
Kyunghun Sung, Seung‐Hwan Lee
Journal of Diabetes Investigation.2025; 16(6): 971. CrossRef

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.

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Cardiometabolic Crossroads: Obesity, Sleep-Disordered Breathing, and Epicardial Adipose Tissue in Heart Failure with Preserved Ejection Fraction – A Mini-Review
Fulvio Cacciapuoti, Ciro Mauro, Valentina Capone, Angelo Sasso, Luca Gaetano Tarquinio, Federico Cacciapuoti
Heart and Mind.2025; 9(2): 147. CrossRef
Empagliflozin in diabetic cardiomyopathy: elucidating mechanisms, therapeutic potentials, and future directions
Aiswarya Jaiswal, Poonam Yadav, Pushkar Singh Rawat, Maninder Kaur, Srivalliputturu Sarath Babu, Amit Khurana, Jasvinder Singh Bhatti, Umashanker Navik
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Yi Liu, Chenfu Shen, Yu Cao
Journal of the American Heart Association.2025;[Epub] CrossRef
Sex Difference in the Association Between Regional Adipose Tissue and Left Ventricular Hypertrophy
In-Jeong Cho, Sang-Eun Lee, Wook-Bum Pyun
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Obesity and its management in primary care setting
Mahmoud Ibrahim, Ebtesam M. Ba-Essa, Jessica A. Alvarez, Jason Baker, Vincenzo Bruni, Avivit Cahn, Antonio Ceriello, Francesco Cosentino, Melanie J. Davies, Francesco De Domenico, Robert H. Eckel, Allon N. Friedman, Jonathan Goldney, Omer Hamtzany, Scott
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Differential Association of Regional Adipose Tissue Deposit with Cardiovascular-Kidney-Metabolic Syndrome
In-Jeong Cho, Sang-Eun Lee, Wook Bum Pyun
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Epicardial Adipose Tissue and Heterogeneity Parameters Combined with Inflammatory Cells to Predict the Value of Heart Failure with Preserved Ejection Fraction Patients Post Myocardial Infarction
Yu-jiao Song, Xiao-ying Zhao, Lu-jing Wang, Ting Ning, Ming-tian Chen, Pei Liu, Si-wen Chen, Xin-xiang Zhao
Cardiovascular Diabetology.2025;[Epub] CrossRef
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
Echocardiography.2024;[Epub] CrossRef
Statin Therapy Mitigates Oxidative Stress in Epicardial and Perivascular Adipose Tissue: A Pilot Study in Cardiac Surgery Patients
Laurentiu Braescu
Timisoara Medical Journal.2024; 2024(1): 1. CrossRef
Beyond weight loss: the potential of glucagon-like peptide-1 receptor agonists for treating heart failure with preserved ejection fraction
Tian-Yu Wang, Qiang Yang, Xin-Yi Cheng, Jun-Can Ding, Peng-Fei Hu
Heart Failure Reviews.2024; 30(1): 17. CrossRef
Predictive value of epicardial adipose tissue volume measured in diagnosis and prognosis of patients with HFPEF
Yunlu Jiang, Li Su
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Huangqi-Danshen decoction improves heart failure by regulating pericardial adipose tissue derived extracellular vesicular miR-27a-3p to activate AMPKα2 mediated mitophagy
Zhaoyang Chen, Meng Zhang, Qiyao Xu, Pengyu Lu, Min Liu, Rui Yin, Xuan Liu, Yang Dai, Xin Gao, Juexiao Gong, Sujie Zhang, Xindong Wang
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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.

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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
A Machine Learning Model for Predicting Prognosis in HCC Patients With Diabetes After TACE
Linxia Wu, Lei Chen, Lijie Zhang, Yiming Liu, Die Ouyang, Wenlong Wu, Yu Lei, Ping Han, Huangxuan Zhao, Chuansheng Zheng
Journal of Hepatocellular Carcinoma.2025; Volume 12: 77. CrossRef
Use of an insulin titration protocol based on continuous glucose monitoring in postoperative cardiac surgery patients with type 2 diabetes and prediabetes: a randomized controlled trial
Sun-Joon Moon, Min-Su Kim, Yun Tae Kim, Ha-Eun Lee, Young-Woo Lee, Su-Ji Lee, Euy-Suk Chung, Cheol-Young Park
Cardiovascular Diabetology.2025;[Epub] 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.

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Biomedical outcomes and cardiovascular risks in Chinese adults with type 2 diabetes in the metabolic management center program: A longitudinal comparative study
Zhanpeng He, Hui Cheng, Zhihui Jia, Zimin Niu, Yu Ting Li, Wenyong Huang, Vivian Yawei Guo, Zhiran Su, Yao Jie Xie, Jie Shen, Harry HX Wang
Journal of Diabetes Investigation.2025; 16(5): 884. CrossRef
Thiamine and METTL14 in Diabetes Management with Intensive Insulin Therapy
Miaoguan Peng, Yingying Zhang, Xiaoshi Weng, Jianfeng Wu, Taizhen Luo, Yanmei Dong, Shiyun Wen, Naifeng Liang, Liangying Zhong, Yaojie Zhai, Yijuan Xie, Yingjun Xie, Yuyi Chen
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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
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Free Radical Biology and Medicine.2024; 213: 293. CrossRef
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Kailu Wang, Shi Zhao, Eric Kam-Pui Lee, Susan Zi-May Yau, Yushan Wu, Chi-Tim Hung, Eng-Kiong Yeoh
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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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Priyanka Sati, Praveen Dhyani, Eshita Sharma, Dharam Chand Attri, Arvind Jantwal, Rajni Devi, Daniela Calina, Javad Sharifi-Rad
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Song Lu, Qun Wang, Hengcheng Lu, Maobin Kuang, Min Zhang, Guotai Sheng, Yang Zou, Xiaoping Peng
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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.

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Investigating the causal association of generalized and abdominal obesity with microvascular complications in patients with type 2 diabetes: A community‐based prospective study
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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)
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Claudia R.L. Cardoso, Nathalie C. Leite, Gil F. Salles
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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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Pregnancy and postpartum cardiometabolic outcomes among women with overt diabetes compared to women with normoglycaemia, gestational diabetes and pre‐existing diabetes: A systematic review and meta‐analysis
Adarsh Pal, Dimple Rawat, Sankeerth Sadananda, Alpesh Goyal, Partha Haldar, Deepali Garg, Yashdeep Gupta, Nikhil Tandon
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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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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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Diagnostics.2022; 12(12): 3094. CrossRef

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).

Citations

Citations to this article as recorded by

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