Diabetes & Metabolism Journal

Original Articles

Basic and Translational Research
Sleeve Gastrectomy with Fundoplication Enhances Metabolic Health in Obese Rats via Ghrelin Pathway Modulation and Multi-Organ Regulation: Xin Li, Aikebaier Aili, Yusujiang Tusuntuoheti, Yusunjiang Aierken, Kelimu Abudureyimu, Weihui Liu; Received May 4, 2025 Accepted November 23, 2025 Published online January 15, 2026; DOI: https://doi.org/10.4093/dmj.2025.0392 [Epub ahead of print]

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Obesity serves as a predominant factor in the progression of metabolic syndrome and type 2 diabetes mellitus. While sleeve gastrectomy (SG) is a well-established surgical intervention, its impact on appetite-regulating hormones, such as ghrelin (GHRL), is limited. Sleeve gastrectomy combined with fundoplication (SGFD) has emerged as a potential strategy to improve metabolic outcomes by modifying both gastric anatomy and gut-brain signaling.
Methods
Sixty-five Sprague-Dawley rats were enrolled. After 8 weeks of high-fat feeding, 48 rats developed diet-induced obesity (DIO). These rats were randomized into four experimental groups: DIO control, sham-operated, SG, and SGFD, alongside a normal control cohort. Biochemical indicators, hormonal fluctuations, and insulin responsiveness were analyzed. Molecular expressions were evaluated through quantitative real-time polymerase chain reaction and Western blotting.
Results
SGFD reduced body weight (−24.7%), food intake (−28.3%), fasting glucose (−37.5%), triglycerides (−42.6%), and serum GHRL (−51.2%) compared with the DIO group (P<0.01). Gastric GHRL, preproghrelin, and ghrelin O-acyltransferase (GOAT) expression were suppressed. Hypothalamic neuropeptide Y (NPY) was downregulated, and AMP-activated protein kinase (AMPK) signaling was robustly enhanced across various tissues. SGFD also improved insulin receptor substrate-1 (IRS-1), glucose transporter type 4 (GLUT4), β-cell function, hepatic lipid oxidation, and brown adipose thermogenesis. SGFD outperformed SG in most metabolic and molecular outcomes (P<0.05).
Conclusion
SGFD provides superior metabolic benefits over SG alone by suppressing GHRL signaling and activating systemic AMPK pathways. SGFD represents a promising surgical strategy for obesity and metabolic syndrome.

Others
Efficacy and Safety of HD-6277, a Novel G Protein-Coupled Receptor 40 Agonist, in Individuals with Type 2 Diabetes Mellitus: A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 2 Clinical Trial: Yong-ho Lee, Kyung Wan Min, Jun Hwa Hong, Soo Lim, Jae Myung Yu, Choon Hee Chung, Jun Sung Moon, Jong Chul Won, Chul Woo Ahn, Jie-Eun Lee, Tae Nyun Kim, Byung-Wan Lee; Received July 17, 2025 Accepted October 11, 2025 Published online December 19, 2025; DOI: https://doi.org/10.4093/dmj.2025.0528 [Epub ahead of print]

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This study assessed the efficacy and safety of HD-6277, a novel oral G protein-coupled receptor 40 (GPR40) agonist in adults with inadequate control of type 2 diabetes mellitus (T2DM).
Methods
This double-blind, randomized, placebo-controlled phase 2 trial recruited 112 individuals aged 18–75 years with T2DM and glycosylated hemoglobin (HbA1c) levels between 7.0% and 10.0% while on diet and exercise alone for at least 8 weeks before screening. Parallel-group randomized trials of HD-6277 (50 and 100 mg groups vs. placebo) were conducted for 12 weeks. The primary outcome was the change in HbA1c levels from baseline to week 12. Secondary outcomes included changes in HbA1c, fasting plasma glucose (FPG), postprandial glucose, insulin, glycoalbumin, and C-peptide at weeks 4, 8, and 12.
Results
At week 12, HD-6277 at 50 and 100 mg demonstrated statistically significant reductions in HbA1c compared to placebo, with least square (LS) mean differences of –0.73% (95% confidence interval [CI], –1.11 to –0.35; P=0.0002) and –0.85% (95% CI, –1.21 to –0.50; P<0.0001), respectively. Both doses also produced clinically meaningful reductions in FPG. Additionally, HD- 6277 at 100 mg significantly increased the insulinogenic index compared to placebo, with an LS mean difference of 1.91 (95% CI, 0.34 to 3.48; P=0.0175). No clinically relevant treatment-related adverse events were observed.
Conclusion
HD-6277 at 50 and 100 mg improved glycemic control and was well-tolerated in adults with T2DM inadequately managed with diet and exercise. GPR40 agonists may offer a promising new therapeutic option for T2DM.

Review

Guideline/Statement/Fact Sheet
Defining Severe Diabetes Mellitus: A Consensus Framework for Grading and Staging Diabetes Based on Pathophysiology and Complications: Jae Hyun Bae, Hun Jee Choe, Ye Seul Yang, Mi Hae Seo, Jong Han Choi, Gyuri Kim, Young Sang Lyu, Jeung Hun Han, Shinae Kang, Won Jun Kim, Kyung-Soo Kim, Young Min Cho, Bong Soo Cha, for the Severe Diabetes Mellitus Task Force of the Korean Diabetes Association; Diabetes Metab J. 2025;49(6):1141-1154. Published online October 28, 2025; DOI: https://doi.org/10.4093/dmj.2025.0739

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Diabetes mellitus comprises a heterogeneous group of metabolic disorders differing in etiology, clinical course, and outcomes. Traditional classifications, such as type 1 and type 2 diabetes mellitus, fail to capture the full heterogeneity, including variation in insulin deficiency, insulin resistance, and complication burden. To address these limitations, we propose the Diabetes Grade–Stage Classification, an integrated system that combines pathophysiology-based grading with complication-based staging. Grading quantifies metabolic dysfunction through the assessment of insulin deficiency and insulin resistance. In parallel, staging assesses the extent of target organ damage, particularly in the cardiovascular, renal, ocular, and nervous systems. Together, this framework enables a comprehensive assessment of disease status, identification of vulnerable or high-risk phenotypes, and implementation of risk-adapted management strategies. Clinically, it facilitates personalized care, promotes collaborative coordination, and strengthens physician–patient communication. Furthermore, this framework provides a scalable structure for integrating disease severity into both individual- and population-level interventions. Although the current criteria for grading and staging are based on expert consensus and selected clinical indicators, such as low C-peptide levels and advanced complications, further validation and refinement are needed. In conclusion, the grading and staging system provides an operational tool for classifying the severity of diabetes mellitus and has the potential to extend life expectancy and improve quality of life for people living with diabetes mellitus.

Citations

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Bridging Evidence and Practice: A Consensus Statement from the Korean Diabetes Association on Diabetes Screening, Pharmacological Treatment and Severe Diabetes
Jong Han Choi, Shinae Kang, Soo-Kyung Kim, Won Jun Kim, Ji Min Kim, Jaehyun Bae, Jae-Seung Yun, Eonju Jeon, Young-Eun Kim, Jae Hyun Bae, Hun Jee Choe, Young Min Cho, Seung-Hyun Ko, Sang Yong Kim, Hae Jin Kim, You-Cheol Hwang, Min Kyong Moon, Suk Chon, Seo
Diabetes & Metabolism Journal.2025; 49(6): 1155. CrossRef

Original Article

Basic and Translational Research
Abnormally Elevated PKCδ Delays Diabetic Wound Healing by Inhibiting the GAD1-GABA Pathway: Peiliang Qin, Peng Zhou, Yating Huang, Binbin Long, Ruikang Gao, Bingjie Zhu, Yiqing Li, Qin Li; Received August 4, 2024 Accepted May 29, 2025 Published online September 8, 2025; DOI: https://doi.org/10.4093/dmj.2024.0450 [Epub ahead of print]

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Diabetic foot ulcer (DFU) represents a challenging complication of diabetes mellitus, characterized by slow healing processes. Protein kinase C delta (PKCδ) has been identified as a significant factor in the pathogenesis of various diabetic complications, including DFU. However, the precise underlying mechanisms remain to be fully elucidated.
Methods
Human umbilical vein endothelial cells (HUVECs) were cultivated under high glucose conditions and PKCδ was knocked down by siRNA. The proliferation, migration, and tube formation of HUVECs were detected. A metabolomics sequencing was done to identify potential metabolites contributing to the changes. HUVECs proliferation, migration, tube formation, and apoptosis were detected after regulating the production of selected metabolite. And finally, the effect of the metabolite on diabetic wound healing was detected.
Results
In vitro, knockdown of PKCδ upregulated glutamate decarboxylase 1 (GAD1) expression and gamma-aminobutyric acid (GABA) levels, which enhanced proliferation, migration, and tube formation and suppressed apoptosis of HUVECs under high glucose conditions. Interestingly, inhibition of GAD1 in normal glucose-treated HUVECs resulted in decreased proliferation, migration, tube formation, and increased apoptosis. Furthermore, in vivo experiments demonstrated that topical administration of GABA accelerated the healing of diabetic wounds in streptozotocin-induced type 2 diabetes mellitus mice, manifested as higher angiogenesis and proliferation.
Conclusion
The inhibition of GAD1-GABA pathway by PKCδ suppresses the proliferation, migration, tube formation and promotes the apoptosis of endothelial cells under high glucose and leads to delayed diabetic wound healing.

Reviews

Complications
Diabetes Mellitus and Infectious Diseases: Current Evidence and Clinical Implications: Taeeun Kim, Sang-Ho Choi; Diabetes Metab J. 2025;49(5):915-933. Published online August 27, 2025; DOI: https://doi.org/10.4093/dmj.2025.0508

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Diabetes mellitus predisposes individuals to a broad spectrum of infections. People with diabetes face a 1.5- to 4-fold increased risk of both common and severe infections, and infections remain the leading cause of morbidity and mortality. Chronic hyperglycemia impairs neutrophil chemotaxis, oxidative burst, and complement activation, while vascular insufficiency and neuropathy compromise tissue perfusion and barrier integrity. These defects, together with altered skin, mucosal, and gut microbiota, influence the marked susceptibility to urinary tract infections (especially renal abscess and emphysematous pyelonephritis), osteomyelitis, diabetic foot infections, pneumonia (including influenza), tuberculosis, skin and soft tissue infections, and lifethreatening syndromes such as emphysematous cholecystitis and rhino-orbital mucormycosis that are almost exclusive to people with diabetes. Outcomes from infections are worse in diabetes. Although the core therapeutic principles align with those for patients without diabetes, management should be individualized. Glycemic control should balance infection risk and hypoglycemia; antimicrobial dosing should account for renal function and drug interactions; and strict antimicrobial stewardship is required. If needed, prompt debridement and multidisciplinary intervention are necessary to mitigate complications and reduce mortality. Preventive care relies on comprehensive vaccination (influenza, pneumococcus, severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], hepatitis B, herpes zoster, and Tdap/Td) and regular foot surveillance with offloading to avert ulceration.

Citations

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Review on the Gut‐Kidney Axis Mechanism and Therapeutic Strategies in Diabetic Nephropathy
Qing Li, Mingrong Cheng, Xiaoyan Zhang
Diabetes/Metabolism Research and Reviews.2026;[Epub] CrossRef
Prim-O-glucosylcimifugin targets Staphylococcus aureus caseinolytic protease P to inhibit α-hemolysin expression and promote healing of MRSA-induced diabetic skin infections
Yan Wang, Shanshan Luo, Xinping Guo, Mengli Jin, Xingye Wang, Mingran Li, Shuang Jiang, Lin Wei, Mingjun Liu, Wu Song
Microbial Pathogenesis.2026; 212: 108296. CrossRef
Preoperative triglyceride–glucose index as a metabolic predictor of surgical site infection after posterior lumbar fusion
Yu Hua, Shaoxing Li, Yuan Jiang, Jinwang Liu
Journal of Orthopaedic Surgery.2026;[Epub] CrossRef
Development and validation of a risk nomogram model for predicting superficial fungal infections in patients with type 2 diabetes mellitus : a cross-sectional study
Yu Li, Guozhong Zhou, Feifei Yang, Rong long, Wei Shi, Yan Dong, Yuanyuan Zhou, Nan Chen, Ying Yang
BMC Infectious Diseases.2026;[Epub] CrossRef
Immunometabolic reprogramming in diabetic osteomyelitis: from mechanisms to therapeutics
Hui Zhang, Zi-Shan Fu, Ying Zhou, Song-Nan Wang, Si-Ying Ye, An-Na Wang, Jun-Tong Liu
Frontiers in Cellular and Infection Microbiology.2025;[Epub] CrossRef
Risk of Acute Cholecystitis Based on Combination of Patient Age, Patient Sex, Leukocytosis, and Sonographic Murphy Sign
Hideaki Ishida, Hiroko Naganuma
Journal of Ultrasound in Medicine.2025;[Epub] CrossRef
Chronic Infections and Diabetes in Africa: A Narrative Review of Pathogen-Associated Metabolic Risk
Olabisi P Lawal, Fortune I Ebiala, Modinat Abayomi, Obiageri Ihuarulam Okeoma, Nana Ama Aduma Amankwah, John O Patrick, Queeneth Eguakun, Aliyu O Olaniyi
Cureus.2025;[Epub] CrossRef

Complications
Clinical Phenotypes of Diabetic Peripheral Neuropathy: Implications for Phenotypic-Based Therapeutics Strategies: Jie-Eun Lee, Jong Chul Won; Diabetes Metab J. 2025;49(4):542-564. Published online July 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0299

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Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus that encompasses a heterogeneous group of conditions with diverse clinical manifestations. Despite its prevalence, no universally established classification or treatment approach is currently available. Recent findings have underscored the role of systemic inflammation, oxidative stress, and neurochemical imbalances in shaping DPN phenotypes, emphasizing the need for phenotype-specific diagnostic and therapeutic approaches. Advanced diagnostic techniques, including magnetic resonance imaging-based neuroimaging and quantitative sensory testing, are emerging as tools for phenotypic characterization. Therapeutic interventions are moving toward precision medicine, with targeted pharmacological and non-pharmacological strategies tailored to specific clinical presentations. Innovations such as digital health platforms, regenerative therapies, and combinatorial pharmacotherapy are promising for addressing primary neuropathic pain and its associated complications. This review synthesizes the current evidence on DPN phenotypes (painful, painless, and mixed forms), their underlying pathophysiological mechanisms, and the efficacy of treatment approaches. A framework for optimizing management strategies is also proposed. By leveraging novel insights into sensory phenotypes and treatment responsiveness, clinicians can adopt DPN phenotype-based treatment models to optimize patient care, improve treatment outcomes, reduce the substantial disease burden, and enhance patient quality of life.

Citations

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Why are we still missing the pain? Rethinking diabetic neuropathy in primary care – lessons from the REGENERAR study
Antonio Alcántara Montero
Future Science OA.2026;[Epub] CrossRef
Plasma Mucin-1 as a Potential Biomarker for Diabetic Peripheral Neuropathy in Type 2 Diabetes
Jae-Hyung Park, Thi Nhi Nguyen, Hye Min Shim, Gyeong Im Yu, Junho Kang, Eun Yeong Ha, Hochan Cho
Biomolecules.2026; 16(1): 128. CrossRef
The association between Apolipoprotein A1, Apolipoprotein B and their ratio with diabetes‐related neuropathy in elderly patients
Iskandar R. Budianto, Ervina Gosal, Tena Djuartina, Alfred Sutrisno
Diabetic Medicine.2026;[Epub] CrossRef
The role of brain mechanisms in diabetic peripheral neuropathy: recent advances and comprehensive analysis
Min Wei, Ye Jiang, Jiayin Shou, Guogang Xing, Min Li
Frontiers in Cellular Neuroscience.2025;[Epub] CrossRef
On a Phenotypic Approach to Diabetic Peripheral Neuropathy (Diabetes Metab J 2025;49:542-64)
Antonio Alcántara Montero
Diabetes & Metabolism Journal.2025; 49(6): 1349. CrossRef
Effects of CXCR1/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in Rat (Diabetes Metab J 2025;49:990-1005)
Heung Yong Jin
Diabetes & Metabolism Journal.2025; 49(6): 1351. CrossRef
Clinical Phenotypes of Diabetic Peripheral Neuropathy: Implications for Phenotypic-Based Therapeutics Strategies (Diabetes Metab J 2025;49:542-64)
Jie-Eun Lee, Jong Chul Won
Diabetes & Metabolism Journal.2025; 49(6): 1354. CrossRef
Precision approach to diabetic peripheral neuropathy: modified nerve decompression surgery and MNGF treatment
Yanji Zhang, Hehua Song, Yang Jian, Silang Cai, Chengliang Deng, Zairong Wei
Frontiers in Medicine.2025;[Epub] CrossRef
Apolipoprotein E genotypes are associated with diabetic peripheral neuropathy in Lebanese adults with type 2 diabetes: a case-control study
Rita Nemr, Sabrina Zidi, Akram Echtay, Eddie Racoubian, Nisrine Beydoun, Wassim Y. Almawi
Frontiers in Endocrinology.2025;[Epub] CrossRef
Neuroinflammation-Based Novel Biomarkers for Early Detection of Diabetic Neuropathy
Jee Hee Yoon, Ho-Cheol Kang
The Journal of Korean Diabetes.2025; 26(4): 222. CrossRef

Others
Differences between Type 2 Diabetes Mellitus and Obesity Management: Medical, Social, and Public Health Perspectives: Soo Lim, Ga Eun Nam, Arya M. Sharma; Diabetes Metab J. 2025;49(4):565-579. Published online June 11, 2025; DOI: https://doi.org/10.4093/dmj.2025.0278

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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.

Citations

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GLP-1 Receptor Agonists: Advances in Mechanism, Therapeutic Applications, and Future Perspectives
Megha Pawar, Chandrashekhar Patil, Zubershaha Fakir, Durgesh Pagar, Sunil Mahajan
BioMed Target Journal.2025; : 2. CrossRef

Original Articles

Metabolic Risk/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; Diabetes Metab J. 2025;49(5):1075-1086. Published online May 23, 2025; DOI: https://doi.org/10.4093/dmj.2024.0518

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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.

Citations

Citations to this article as recorded by

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; 62(8): 1347. 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.

Citations

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Present Advances and Emerging Challenges in Kidney Xenotransplantation
Kazuaki Yamanaka, Yoichi Kakuta, Shuji Miyagawa, Kentaro Inoue, Soichi Matsumura, Shota Fukae, Masataka Kawamura, Shigeaki Nakazawa, Kenichi Kobayashi, Susumu Kageyama, Norio Nonomura
Journal of Clinical Medicine.2026; 15(5): 1692. CrossRef
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
Harmonizing International Regulatory Standards for Porcine Endogenous Retrovirus (PERV) Screening in Genetically Modified Porcine Donors for First‐in‐Human Pancreatic Islet Xenotransplantation
Muhammad Umer Suleman, Muhammad Mursaleen, Umer Khalil
Xenotransplantation.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.

Citations

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Quantitative evaluation of the topographical maps of three-dimensional choroidal vascularity index in gestational diabetes mellitus: a cross-sectional observational study
Ligang Jiang, Yimei Ji, Xin Jiang, Yune Zhao
BMC Pregnancy and Childbirth.2026;[Epub] CrossRef
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
Postprandial C-Peptide to Glucose Ratio as a Promising Systemic Marker of Diabetic Retinopathy in Type 2 Diabetes
Zhaoxia Zheng, Nianen Liu, Yue Zhang, Xiaoya Gu, Hui Li, Xiaobing Yu
Translational Vision Science & Technology.2025; 14(7): 27. CrossRef
The Correlation Between Macular Vessel Density and Its Clinical Parameters in Diabetes Mellitus Type 2
Nadia Dewi, Muhammad Arfan, Herisa Rahmasari, Mutiara Putri, Rulli Rosandi
Clinical Ophthalmology.2025; Volume 19: 3113. CrossRef
Comment on: “Risk factors and incidence of macular edema in eyes with retinal vein occlusion after uneventful cataract surgery: The MEVO study”
Xianmei Zhang, Jing Chen
Indian Journal of Ophthalmology.2025; 73(11): 1698. CrossRef
Prevalence and determinants of comorbidities among patients with type 2 diabetes mellitus in Nepal: a cross-sectional study
Nitendra Kumar Chaurasia, Md Mothashin, Md Golam Hossain
BMC Endocrine Disorders.2025;[Epub] 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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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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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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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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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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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
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Claudia R.L. Cardoso, Nathalie C. Leite, Gil F. Salles
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Unraveling shared risk factors for diabetic foot ulcer: a comprehensive Mendelian randomization analysis
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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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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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Jayne Feter, Natan Feter, Rodrigo Leal-Menezes, Pedro C. Hallal, Daniel Umpierre
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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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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

Comparison of Insulin Titration Strategies for Glycemic Control in Type 2 Diabetes: A Systematic Review and Network Meta-analysis
Kansak Boonpattharatthiti, Kirana Wechkunanukul, Noramon Mayang, E Lyn Lee, Anjana Fuangchan, Alice Y.Y. Cheng, Nathorn Chaiyakunapruk, Teerapon Dhippayom
Diabetes Care.2025; 48(5): 837. CrossRef
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 (?)
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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.

Reviews

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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Abstract PDF PubReader ePub

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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Technology/Device
Present and Future of Digital Health in Diabetes and Metabolic Disease: Sang Youl Rhee, Chiweon Kim, Dong Wook Shin, Steven R. Steinhubl; Diabetes Metab J. 2020;44(6):819-827. Published online December 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0088

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Abstract PDF PubReader ePub

The use of information and communication technology (ICT) in medical and healthcare services goes beyond everyday life. Expectations of a new medical environment, not previously experienced by ICT, exist in the near future. In particular, chronic metabolic diseases such as diabetes and obesity, have a high prevalence and high social and economic burden. In addition, the continuous evaluation and monitoring of daily life is important for effective treatment and management. Therefore, the wide use of ICTbased digital health systems is required for the treatment and management of these diseases. In this article, we compiled a variety of digital health technologies introduced to date in the field of diabetes and metabolic diseases.

Citations

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Original Articles

Complications
Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study: Kyoung Jin Kim, Jimi Choi, Jae Hyun Bae, Kyeong Jin Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2021;45(3):368-378. Published online October 20, 2020; DOI: https://doi.org/10.4093/dmj.2020.0046

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Background
To evaluate the association of time to reach the target glycosylated hemoglobin (HbA1c) level with long-term durable glycemic control and risk of diabetic complications in patients with newly diagnosed type 2 diabetes mellitus (T2DM).
Methods
In a longitudinal observational cohort, 194 patients with T2DM newly diagnosed between January 2011 and March 2013 were followed up over 6 years. Patients were classified according to the time needed to reach the target HbA1c (<7.0%): <3, 3 to 6 (early achievement group), and ≥6 months (late achievement group). Risks of microvascular complications including diabetic retinopathy, nephropathy, and neuropathy as well as macrovascular events including ischemic heart disease, ischemic stroke, and peripheral arterial disease were assessed by multivariable Cox proportional hazards analysis.
Results
During a median follow-up of 6.53 years, 66 microvascular and 14 macrovascular events occurred. Maintenance of durable glycemic control over 6 years was more likely in the early achievement groups than in the late achievement group (34.5%, 30.0%, and 16.1% in <3, 3 to 6, and ≥6 months, respectively, P=0.039). Early target HbA1c achievement was associated with lower risk of composite diabetic complications (adjusted hazard ratio [HR, 0.47; 95% confidence interval [CI], 0.26 to 0.86 in <3 months group) (adjusted HR, 0.50; 95% CI, 0.23 to 1.10 in 3 to 6 months group, in reference to ≥6 months group). Similar trends were maintained for risks of microvascular and macrovascular complications, although statistical significance was not reached for macrovascular complications.
Conclusion
Early target HbA1c achievement was associated with long-term durable glycemic control and reduced risk of diabetic complications in newly diagnosed T2DM.

Citations

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Complications
Association between Sleep Quality and Painless Diabetic Peripheral Neuropathy Assessed by Current Perception Threshold in Type 2 Diabetes Mellitus: Dughyun Choi, Bo-Yeon Kim, Chan-Hee Jung, Chul-Hee Kim, Ji-Oh Mok; Diabetes Metab J. 2021;45(3):358-367. Published online August 6, 2020; DOI: https://doi.org/10.4093/dmj.2019.0219

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Background

It is known that the painful sensation of diabetic peripheral neuropathy (DPN) results in sleep problems in type 2 diabetes mellitus (T2DM). However, it is not known that the painless DPN also is associated with poor sleep quality in T2DM. The purpose of the current study was to investigate the association between painless DPN and poor sleep quality in T2DM.

Methods

A total of 146 patients of T2DM who do not have any painful symptoms of DPN were recruited into the study. Among the patients, painless DPN was diagnosed by using the current perception threshold test. Sleep quality was assessed using the Pittsburgh Sleep Quality Index questionnaire.

Results

The percentage of painless DPN was significantly higher in the poor sleep quality group than the good sleep quality group (70.0% vs. 35.5%, P<0.001). In the subscale results, stimulus values at 2,000 Hz, hypoesthesia and hyperesthesia were more common in the poor sleep quality group than in the good sleep quality group (45.7% vs. 25.0%, P=0.009; 34.3% vs. 18.4%, P=0.029; 40.0% vs. 19.7%, P=0.007, respectively). The association of painless DPN and poor sleep quality remained significant after adjustment for significant covariates (odds ratio, 3.825; 95% confidence interval, 1.674 to 8.742; P<0.001).

Conclusion

The current study showed that painless DPN was associated with poor sleep quality. Future studies are required to clarify the pathophysiologic causal relationship between painless DPN and sleep quality.

Citations

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Metabolic Risk/Epidemiology
Effect of Sarcopenia and Body Shape on Cardiovascular Disease According to Obesity Phenotypes: Hyun-Woong Cho, Wankyo Chung, Shinje Moon, Ohk-Hyun Ryu, Min Kyung Kim, Jun Goo Kang; Diabetes Metab J. 2021;45(2):209-218. Published online July 10, 2020; DOI: https://doi.org/10.4093/dmj.2019.0223

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Abstract PDF Supplementary Material PubReader ePub

Background

This study aimed to assess the effects of sarcopenia and A Body Shape Index (ABSI) on cardiovascular disease (CVD) risk according to obesity phenotypes.

Methods

We used data from the National Health and Nutrition Examination Survey 1999 to 2012. A total of 25,270 adults were included and classified into the following groups: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). Sarcopenia was defined as the appendicular skeletal mass index <7 kg/m² in men and <5.5kg/m² in women. A multivariate logistic regression analysis was performed to evaluate the odds ratio (OR) of sarcopenia and ABSI for CVD events according to the obesity phenotype.

Results

The MHNW participants with sarcopenia had higher risk for CVD than those without sarcopenia (OR, 2.69; 95% confidence interval [CI], 1.56 to 4.64). In the analysis with MHNW participants without sarcopenia as a reference, the participants with sarcopenia showed a higher OR for CVD than those without sarcopenia in both MHO (OR in participants without sarcopenia, 3.31; 95% CI, 1.94 to 5.64) (OR in participants with sarcopenia, 8.59; 95% CI, 2.63 to 28.04) and MUO participants (OR in participants without sarcopenia, 5.11; 95% CI, 3.21 to 8.15) (OR in participants with sarcopenia, 8.12; 95% CI, 4.04 to 16.32). Participants within the second and third tertiles of ABSI had higher ORs for CVDs than the counterpart of obesity phenotypes within the first tertile.

Conclusion

These results suggest that clinical approaches that consider muscle and body shape are required.

Citations

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Basic Research
Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell: Kyung-Soo Kim, Yeon Kyung Choi, Mi Jin Kim, Jung Wook Hwang, Kyunghoon Min, Sang Youn Jung, Soo-Kyung Kim, Yong-Soo Choi, Yong-Wook Cho; Diabetes Metab J. 2021;45(2):260-269. Published online July 10, 2020; DOI: https://doi.org/10.4093/dmj.2019.0191

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Background

Umbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell.

Methods

Insulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell.

Results

Glucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance.

Conclusion

UC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

Citations

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Type 1 Diabetes
Age at Diagnosis and the Risk of Diabetic Nephropathy in Young Patients with Type 1 Diabetes Mellitus: Jong Ha Baek, Woo Je Lee, Byung-Wan Lee, Soo Kyoung Kim, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim; Diabetes Metab J. 2021;45(1):46-54. Published online July 10, 2020; DOI: https://doi.org/10.4093/dmj.2019.0134

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Background

The aim of this study was to evaluate characteristics and risk of diabetic complications according to age at diagnosis among young adults with type 1 diabetes mellitus (T1DM).

Methods

A total of 255 T1DM patients aged less than 40 years were included. Patients were categorized into three groups (<20, 20 to 29, and 30 to 40 years) according to age at diagnosis. Diabetic nephropathy (DN) was defined when spot urine-albumin creatinine ratio was 300 mg/g or more and/or estimated glomerular filtration ratio (eGFR) level was 60 mL/min/1.73 m² or less.

Results

Median age at diagnosis was 25 years and disease duration was 14 years. Individuals diagnosed with T1DM at childhood/adolescent (age <20 years) had lower stimulated C-peptide levels. They received more intensive insulin treatment with higher total daily insulin doses compared to older onset groups. The prevalence of DN was higher in the childhood/adolescent-onset group than in older onset groups (25.3% vs. 15.3% vs. 9.6%, P=0.022). The eGFR was inversely associated with disease duration whilst the degree of decrease was more prominent in the childhood/adolescent-onset group than in the later onset group (aged 30 to 40 years; P<0.001). Childhood/adolescent-onset group was independently associated with the risk of DN compared to the older onset group (aged 30 to 40 years; odds ratio, 3.47; 95% confidence interval, 1.45 to 8.33; P=0.005).

Conclusion

In individuals with childhood/adolescent-onset T1DM, the reduction in renal function is more prominent with disease duration. Early age-onset T1DM is an independent risk of DN.

Citations

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Others
Can Habitual Exercise Help Reduce Serum Concentrations of Lipophilic Chemical Mixtures? Association between Physical Activity and Persistent Organic Pollutants: Yu-Mi Lee, Ji-Yeon Shin, Se-A Kim, David R. Jacobs, Duk-Hee Lee; Diabetes Metab J. 2020;44(5):764-774. Published online May 11, 2020; DOI: https://doi.org/10.4093/dmj.2019.0158

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Background

Low-dose persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs), have emerged as a new risk factor of many chronic diseases. As serum concentrations of POPs in humans are mainly determined by both their release from adipose tissue to circulation and their elimination from circulation, management of these internal pathways may be important in controlling the serum concentrations of POPs. As habitual physical activity can increase the elimination of POPs from circulation, we evaluated whether chronic physical activity is related to low serum POP concentrations.

Methods

A cross-sectional study of 1,850 healthy adults (age ≥20 years) without cardio-metabolic diseases who participated in the U.S. National Health and Nutrition Examination Survey 1999 to 2004 was conducted. Information on moderate or vigorous leisure-time physical activity was obtained based on questionnaires. Serum concentrations of OCPs and polychlorinated biphenyls were investigated as typical POPs.

Results

Serum concentrations of OCPs among physically active subjects were significantly lower than those among physically inactive subjects (312.8 ng/g lipid vs. 538.0 ng/g lipid, P<0.001). This difference was maintained after adjustment for potential confounders. When analyses were restricted to physically active subjects, there were small decreases in the serum concentrations of OCPs with increasing duration of physical activity, showing a curvilinear relationship over the whole range of physical activity (P_quadratic <0.001). In analyses stratified by age, sex, body mass index, and smoking status, a strong inverse association was similarly observed among all subgroups.

Conclusion

Physical activity may assist in decreasing serum concentrations of lipophilic chemical mixtures such as OCPs.

Citations

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Brief Report

Complications
Acute Hyperglycemic Crises with Coronavirus Disease-19: Case Reports: Na-young Kim, Eunyeong Ha, Jun Sung Moon, Yong-Hoon Lee, Eun Young Choi; Diabetes Metab J. 2020;44(2):349-353. Published online April 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0091

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Since the first case was contracted by coronavirus disease-19 (COVID-19) in Daegu, Korea in February 2020, about 6,800 cases and 130 deaths have been reported on April 9, 2020. Recent studies have reported that patients with diabetes showed higher mortality and they had a worse prognosis than the group without diabetes. In poorly controlled patients with diabetes, acute hyperglycemic crises such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) also might be precipitated by COVID-19. Thus, intensive monitoring and aggressive supportive care should be needed to inadequately controlled patients with diabetes and COVID-19 infection. Here, we report two cases of severe COVID-19 patients with acute hyperglycemic crises in Korea.

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Original Articles

Metabolic Risk/Epidemiology
Intra-Abdominal Fat and High Density Lipoprotein Cholesterol Are Associated in a Non-Linear Pattern in Japanese-Americans: Sun Ok Song, You-Cheol Hwang, Steven E. Kahn, Donna L. Leonetti, Wilfred Y. Fujimoto, Edward J. Boyko; Diabetes Metab J. 2020;44(2):277-285. Published online March 10, 2020; DOI: https://doi.org/10.4093/dmj.2019.0008

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Background

We describe the association between high density lipoprotein cholesterol (HDL-C) concentration and computed tomography (CT)-measured fat depots.

Methods

We examined the cross-sectional associations between HDL-C concentration and intra-abdominal (IAF), abdominal subcutaneous (SCF), and thigh fat (TF) areas in 641 Japanese-American men and women. IAF, SCF, and TF were measured by CT at the level of the umbilicus and mid-thigh. The associations between fat area measurements and HDL-C were examined using multivariate linear regression analysis adjusting for age, sex, diabetes family history, homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Non-linearity was assessed using fractional polynomials.

Results

Mean±standard deviation of HDL-C concentration and IAF in men and women were 1.30±0.34 mg/dL, 105±55.3 cm², and 1.67±0.43 mg/dL, 74.4±46.6 cm² and differed significantly by gender for both comparisons (P<0.001). In univariate analysis, HDL-C concentration was significantly associated with CT-measured fat depots. In multivariate analysis, IAF was significantly and non-linearly associated with HDL-C concentration adjusted for age, sex, BMI, HOMA-IR, SCF, and TF (IAF: β=−0.1012, P<0.001; IAF²: β=0.0008, P<0.001). SCF was also negatively and linearly associated with HDL-C (β=−0.4919, P=0.001).

Conclusion

HDL-C does not linearly decline with increasing IAF in Japanese-Americans. A more complex pattern better fits this association.

Citations

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Study on the correlation between triglyceride glucose index, triglyceride glucose index to high-density lipoprotein cholesterol ratio, and the risk of diabetes in nonalcoholic fatty liver disease
Tao Sun, Jun Liu
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Yansu Wang, Yiting Xu, Tingting Hu, Yunfeng Xiao, Yufei Wang, Xiaojing Ma, Haoyong Yu, Yuqian Bao
Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 121. CrossRef
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Anna Kim, Eun-yeob Kim, Jaeyoung Kim
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Computed tomography-based investigation of the correlation of abdominal fat areas with metabolic syndrome
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Lower High-Density Lipoprotein Cholesterol Concentration Is Independently Associated with Greater Future Accumulation of Intra-Abdominal Fat
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Endocrinology and Metabolism.2021; 36(4): 835. CrossRef

Metabolic Risk/Epidemiology
Glucose Effectiveness from Short Insulin-Modified IVGTT and Its Application to the Study of Women with Previous Gestational Diabetes Mellitus: Micaela Morettini, Carlo Castriota, Christian Göbl, Alexandra Kautzky-Willer, Giovanni Pacini, Laura Burattini, Andrea Tura; Diabetes Metab J. 2020;44(2):286-294. Published online January 13, 2020; DOI: https://doi.org/10.4093/dmj.2019.0016

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Background

This study aimed to design a simple surrogate marker (i.e., predictor) of the minimal model glucose effectiveness (S_G), namely calculated S_G (CS_G), from a short insulin-modified intravenous glucose tolerance test (IM-IVGTT), and then to apply it to study women with previous gestational diabetes mellitus (pGDM).

Methods

CS_G was designed using the stepwise model selection approach on a population of subjects (n=181) ranging from normal tolerance to type 2 diabetes mellitus (T2DM). CS_G was then tested on a population of women with pGDM (n=57). Each subject underwent a 3-hour IM-IVGTT; women with pGDM were observed early postpartum and after a follow-up period of up to 7 years and classified as progressors (PROG) or non-progressors (NONPROG) to T2DM. The minimal model analysis provided a reference S_G.

Results

CS_G was described as CS_G=1.06×10⁻²+5.71×10⁻²×K_G/G_peak, K_G being the mean slope (absolute value) of loge glucose in 10–25- and 25–50-minute intervals, and G_peak being the maximum of the glucose curve. Good agreement between CS_G and S_G in the general population and in the pGDM group, both at baseline and follow-up (even in PROG and NONPROG subgroups), was shown by the Bland-Altman plots (<5% observations outside limits of agreement), and by the test for equivalence (equivalence margin not higher than one standard deviation). At baseline, the PROG subgroup showed significantly lower S_G and CS_G values compared to the NONPROG subgroup (P<0.03).

Conclusion

CS_G is a valid S_G predictor. In the pGDM group, glucose effectiveness appeared to be impaired in women progressing to T2DM.

Citations

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Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus
So-Yeon Kim, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyung-Soo Kim
Diabetes & Metabolism Journal.2022; 46(1): 140. CrossRef
Unraveling the Factors Determining Development of Type 2 Diabetes in Women With a History of Gestational Diabetes Mellitus Through Machine-Learning Techniques
Ludovica Ilari, Agnese Piersanti, Christian Göbl, Laura Burattini, Alexandra Kautzky-Willer, Andrea Tura, Micaela Morettini
Frontiers in Physiology.2022;[Epub] CrossRef
The Clinical Characteristics of Gestational Diabetes Mellitus in Korea: A National Health Information Database Study
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
Endocrinology and Metabolism.2021; 36(3): 628. CrossRef

Cardiovascular Risk/Epidemiology
Impact of Diabetes Control on Subclinical Atherosclerosis: Analysis from Coronary Computed Tomographic Angiography Registry: Gyung-Min Park, Chang Hoon Lee, Seung-Whan Lee, Sung-Cheol Yun, Young-Hak Kim, Yong-Giun Kim, Ki-Bum Won, Soe Hee Ann, Shin-Jae Kim, Dong Hyun Yang, Joon-Won Kang, Tae-Hwan Lim, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Hong-Kyu Kim, Jaewon Choe, Sang-Gon Lee; Diabetes Metab J. 2020;44(3):470-479. Published online November 22, 2019; DOI: https://doi.org/10.4093/dmj.2019.0073

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Background

There are limited data on the impact of diabetes control on the risk of subclinical coronary atherosclerosis.

Methods

We analyzed 6,434 consecutive asymptomatic individuals without previous history of coronary artery disease who underwent coronary computed tomographic angiography (CCTA) (mean age, 53.7±7.6 years and 4,694 men [73.0%]). The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Study participants were categorized as normal (n=5,319), controlled diabetes (glycosylated hemoglobin [HbA1c] <7%, n=747), or uncontrolled diabetes (HbA1c ≥7%, n=368), respectively.

Results

Compared with normal individuals, there were no statistically significant differences in the risk of for any atherosclerotic plaque (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.98 to 1.38; P=0.086) and significant coronary artery stenosis (OR, 1.08; 95% CI, 0.82 to 1.42; P=0.583) in controlled diabetic individuals. In contrast, uncontrolled diabetic individuals had consistently higher risks of any atherosclerotic plaque (OR, 2.16; 95% CI, 1.70 to 2.75; P<0.001) and significant coronary artery stenosis (OR, 3.34; 95% CI, 2.52 to 4.43; P<0.001) than normal individuals. During a follow-up of median 5.4 years, there was no significant difference in cardiac events between normal and controlled diabetic individuals (P=0.365). However, uncontrolled diabetes was associated with an increased risk of cardiac events compared with normal individuals (P<0.001) and controlled diabetic individuals (P=0.023).

Conclusion

Asymptomatic uncontrolled diabetes was associated with significant subclinical coronary atherosclerosis with subsequent high risk for cardiac events.

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Review

Others
Mitochondrial Toxins and Healthy Lifestyle Meet at the Crossroad of Hormesis: Yu-Mi Lee, Duk-Hee Lee; Diabetes Metab J. 2019;43(5):568-577. Published online October 24, 2019; DOI: https://doi.org/10.4093/dmj.2019.0143

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Mitochondrial function is crucial for the maintenance of cellular homeostasis under physiological and stress conditions. Thus, chronic exposure to environmental chemicals that affect mitochondrial function can have harmful effects on humans. We argue that the concept of hormesis should be revisited to explain the non-linear responses to mitochondrial toxins at a low-dose range and develop practical methods to protect humans from the negative effects of mitochondrial toxins. Of the most concern to humans are lipophilic chemical mixtures and heavy metals, owing to their physical properties. Even though these chemicals tend to demonstrate no safe level in humans, a non-linear dose-response has been also observed. Stress response activation, i.e., hormesis, can explain this non-linearity. Recently, hormesis has reemerged as a unifying concept because diverse stressors can induce similar stress responses. Besides potentially harmful environmental chemicals, healthy lifestyle interventions such as exercise, calorie restriction (especially glucose), cognitive stimulation, and phytochemical intake also activate stress responses. This conceptual link can lead to the development of practical methods that counterbalance the harm of mitochondrial toxins. Unlike chemical hormesis with its safety issues, the activation of stress responses via lifestyle modification can be safely used to combat the negative effects of mitochondrial toxins.

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Original Articles

Drug/Regimen
An Electronic Health Record-Integrated Computerized Intravenous Insulin Infusion Protocol: Clinical Outcomes and in Silico Adjustment: Sung Woon Park, Seunghyun Lee, Won Chul Cha, Kyu Yeon Hur, Jae Hyeon Kim, Moon-Kyu Lee, Sung-Min Park, Sang-Man Jin; Diabetes Metab J. 2020;44(1):56-66. Published online October 21, 2019; DOI: https://doi.org/10.4093/dmj.2018.0227

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Background

We aimed to describe the outcome of a computerized intravenous insulin infusion (CII) protocol integrated to the electronic health record (EHR) system and to improve the CII protocol in silico using the EHR-based predictors of the outcome.

Methods

Clinical outcomes of the patients who underwent the CII protocol between July 2016 and February 2017 and their matched controls were evaluated. In the CII protocol group (n=91), multivariable binary logistic regression analysis models were used to determine the independent associates with a delayed response (taking ≥6.0 hours for entering a glucose range of 70 to 180 mg/dL). The CII protocol was adjusted in silico according to the EHR-based parameters obtained in the first 3 hours of CII.

Results

Use of the CII protocol was associated with fewer subjects with hypoglycemia alert values (P=0.003), earlier (P=0.002), and more stable (P=0.017) achievement of a glucose range of 70 to 180 mg/dL. Initial glucose level (P=0.001), change in glucose during the first 2 hours (P=0.026), and change in insulin infusion rate during the first 3 hours (P=0.029) were independently associated with delayed responses. Increasing the insulin infusion rate temporarily according to these parameters in silico significantly reduced delayed responses (P<0.0001) without hypoglycemia, especially in refractory patients.

Conclusion

Our CII protocol enabled faster and more stable glycemic control than conventional care with minimized risk of hypoglycemia. An EHR-based adjustment was simulated to reduce delayed responses without increased incidence of hypoglycemia.

Citations

Citations to this article as recorded by

Response: An Electronic Health Record-Integrated Computerized Intravenous Insulin Infusion Protocol: Clinical Outcomes and in Silico Adjustment (Diabetes Metab J 2020;44:56–66)
Sung Woon Park, Seunghyun Lee, Won Chul Cha, Kyu Yeon Hur, Jae Hyeon Kim, Moon-Kyu Lee, Sung-Min Park, Sang-Man Jin
Diabetes & Metabolism Journal.2020; 44(2): 358. CrossRef
Letter: An Electronic Health Record-Integrated Computerized Intravenous Insulin Infusion Protocol: Clinical Outcomes and in Silico Adjustment (Diabetes Metab J 2020;44:56–66)
Dongwon Yi
Diabetes & Metabolism Journal.2020; 44(2): 354. CrossRef

Clinical Care/Education
Impact of Continuous Care on Health Outcomes and Cost for Type 2 Diabetes Mellitus: Analysis Using National Health Insurance Cohort Database: Ji Hyun Nam, Changwoo Lee, Nayoung Kim, Keun Young Park, Jeonghoon Ha, Jaemoon Yun, Dong Wook Shin, Euichul Shin; Diabetes Metab J. 2019;43(6):776-784. Published online October 21, 2019; DOI: https://doi.org/10.4093/dmj.2018.0189

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Background

The objective of the study was to determine the impact of continuous care on health outcomes and cost of type 2 diabetes mellitus (T2DM) in Korea.

Methods

A nationwide retrospective, observational case-control study was conducted. Continuity of treatment was measured using Continuity of Care (COC) score. Information of all patients newly diagnosed with T2DM in 2004 was retrieved from the National Health Insurance database for the period of 2002 to 2013. The study examined 2,373 patients after applying exclusion criteria, such as for patients who died from conditions not related to T2DM. Statistical analyses were performed using frequency distribution, simple analysis (t-test and chi-squared test), and multi-method analysis (simple linear regression, logistic regression, and survival analysis).

Results

The overall COC score was 0.8±0.24. The average incidence of diabetic complications was 0.39 per patient with a higher COC score, whereas it was 0.49 per patient with a lower COC score. In both survival and logistic analyses, patients who had high COC score were significantly less likely to have diabetic complications (hazard ratio, 0.69; 95% confidence interval, 0.54 to 0.88). The average medical cost was approximately 3,496 United States dollar (USD) per patient for patients with a higher COC score, whereas it was 3,973 USD per patient for patients with a lower COC score during the 2006 to 2013 period, with a difference of around 477 USD, which is statistically significant after adjusting for other factors (β=−0.152).

Conclusion

Continuity of care for diabetes significantly reduced health complications and medical costs from patients with T2DM.

Citations

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Continuity of care for patients with hypertension or diabetes mellitus reduced medical utilizations, total medical costs, and cardiovascular events based on the Korean NHIS-HEALS cohort
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Juhee Lee, Eunyoung Choi, Eunjung Choo, Siachalinga Linda, Eun Jin Jang, Iyn-Hyang Lee
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Kam Suen Chan, Eric Yuk Fai Wan, Weng Yee Chin, Esther Yee Tak Yu, Ivy Lynn Mak, Will Ho Gi Cheng, Margaret Kay Ho, Cindy Lo Kuen Lam
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Clinical Study Using Healthcare Claims Database
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Epidemiology
Diabetes Mellitus and Cause-Specific Mortality: A Population-Based Study: Sen Li, Jiaxin Wang, Biao Zhang, Xinyi Li, Yuan Liu; Diabetes Metab J. 2019;43(3):319-341. Published online April 19, 2019; DOI: https://doi.org/10.4093/dmj.2018.0060

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Background

To investigate whether diabetes contributes to mortality for major types of diseases.

Methods

Six National Health and Nutrition Examination Survey data cycles (1999 to 2000, 2001 to 2002, 2003 to 2004, 2005 to 2006, 2007 to 2008, and 2009 to 2010) and their linked mortality files were used. A population of 15,513 participants was included according to the availability of diabetes and mortality status.

Results

Participants with diabetes tended to have higher all-cause mortality and mortality due to cardiovascular disease, cancer, chronic lower respiratory diseases, cerebrovascular disease, influenza and pneumonia, and kidney disease. Confounder-adjusted Cox proportional hazard models showed that both diagnosed diabetes category (yes or no) and diabetes status (diabetes, prediabetes, or no diabetes) were associated with all-cause mortality and with mortality due to cardiovascular disease, chronic lower respiratory diseases, influenza and pneumonia, and kidney disease. No associations were found for cancer-, accidents-, or Alzheimer's disease-related mortality.

Conclusion

The current study's findings provide epidemiological evidence that diagnosed diabetes at the baseline is associated with increased mortality risk due to cardiovascular disease, chronic lower respiratory diseases, influenza and pneumonia, and kidney disease, but not with cancer or Alzheimer's disease.

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International Journal of Diabetes in Developing Countries.2025; 45(4): 1078. CrossRef
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The Lancet Regional Health - Europe.2025; 48: 101147. CrossRef
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Food & Medicine Homology.2025; 2(3): 9420068. CrossRef
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Diabetes, Metabolic Syndrome and Obesity.2025; Volume 18: 135. CrossRef
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Short Communication

Complications
Glycosylated Hemoglobin in Subjects Affected by Iron-Deficiency Anemia: Jari Intra, Giuseppe Limonta, Fabrizio Cappellini, Maria Bertona, Paolo Brambilla; Diabetes Metab J. 2019;43(4):539-544. Published online November 28, 2018; DOI: https://doi.org/10.4093/dmj.2018.0072

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Previous studies have suggested that iron-deficiency anemia affects glycosylated hemoglobin (HbA1c) measurements, but the results were contradictory. We conducted a retrospective case-control study to determine the effects of iron deficiency on HbA1c levels. Starting with the large computerized database of the Italian Hospital of Desio, including data from 2000 to 2016, all non-pregnant individuals older than 12 years of age with at least one measurement of HbA1c, cell blood count, ferritin, and fasting blood glucose on the same date of blood collection were enrolled. A total of 2,831 patients met the study criteria. Eighty-six individuals were diagnosed with iron-deficiency anemia, while 2,745 had a normal iron state. The adjusted means of HbA1c were significantly higher in anemic subjects (5.59% [37.37 mmol/mol]), than those measured in individuals without anemia (5.34% [34.81 mmol/mol]) (P<0.0001). These results suggest that clinicians should be cautious about diagnosing prediabetes and diabetes in individuals with anemia.

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Original Articles

Clinical Diabetes and Therapeutics
Hospital-Based Korean Diabetes Prevention Study: A Prospective, Multi-Center, Randomized, Open-Label Controlled Study: Sang Youl Rhee, Suk Chon, Kyu Jeung Ahn, Jeong-Taek Woo; Diabetes Metab J. 2019;43(1):49-58. Published online November 2, 2018; DOI: https://doi.org/10.4093/dmj.2018.0033

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Background

The prevalence of diabetes mellitus (DM) continues to increase, and the disease burden is the highest of any medical condition in Korea. However, large-scale clinical studies have not yet conducted to establish the basis for diabetes prevention in Korea.

Methods

The hospital-based Korean Diabetes Prevention Study (H-KDPS) is a prospective, multi-center, randomized, open-label controlled study conducted at university hospitals for the purpose of gathering data to help in efforts to prevent type 2 DM. Ten university hospitals are participating, and 744 subjects will be recruited. The subjects are randomly assigned to the standard care group, lifestyle modification group, or metformin group, and their clinical course will be observed for 36 months.

Results

All intervention methodologies were developed, validated, and approved by Korean Diabetes Association (KDA) multi-disciplinary team members. The standard control group will engage in individual education based on the current KDA guidelines, and the lifestyle modification group will participate in a professionally guided healthcare intervention aiming for ≥5% weight loss. The metformin group will begin dosing at 250 mg/day, increasing to a maximum of 1,000 mg/day. The primary endpoint of this study is the cumulative incidence of DM during the 3 years after randomization.

Conclusion

The H-KDPS study is the first large-scale clinical study to establish evidence-based interventions for the prevention of type 2 DM in Koreans. The evidence gathered by this study will be useful for enhancing the health of Koreans and improving the stability of the Korean healthcare system (Trial registration: CRIS KCT0002260, NCT02981121).

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Obesity and Metabolic Syndrome
Comparison of Competitive Models of Metabolic Syndrome Using Structural Equation Modeling: A Confirmatory Factor Analysis: Karimollah Hajian-Tilaki; Diabetes Metab J. 2018;42(5):433-441. Published online October 22, 2018; DOI: https://doi.org/10.4093/dmj.2018.0010

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Background

The purpose of this study was to apply the structural equation modeling (SEM) to compare the fitness of different competing models (one, two, and three factors) of the metabolic syndrome (MetS) in Iranian adult population.

Methods

Data are given on the cardiometabolic risk factors of 841 individuals with nondiabetic adults from a cross-sectional population-based study of glucose, lipids, and MetS in the north of Iran. The three conceptual hypothesized models (single factor, two correlated factors, and three correlated latent factors) were evaluated by using confirmatory factor analysis with the SEM approach. The summary statistics of correlation coefficients and the model summary fitting indexes were calculated.

Results

The findings show that a single-factor model and a two-correlated factor model had a poorer summary fitting index compared with a three-correlated factor model. All fitting criteria met the conceptual hypothesized three-correlated factor model for both sexes. However, the correlation structure between the three underlying constructs designating the MetS was higher in women than in men.

Conclusion

These results indicate the plausibility of the pathophysiology and etiology of MetS being multifactorial, rather than a single factor, in a nondiabetic Iranian adult population.

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Complications
Association between Serum Cystatin C and Vascular Complications in Type 2 Diabetes Mellitus without Nephropathy: Hye Jeong Kim, Dong Won Byun, Kyoil Suh, Myung Hi Yoo, Hyeong Kyu Park; Diabetes Metab J. 2018;42(6):513-518. Published online October 15, 2018; DOI: https://doi.org/10.4093/dmj.2018.0006

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Background

Recent studies have correlated serum cystatin C (CysC) with vascular complications, but few studies have investigated this correlation in diabetes patients without nephropathy. This study aimed to evaluate if higher serum CysC levels increase the risk for vascular complications in type 2 diabetes mellitus patients with normal renal function or mild renal impairment.

Methods

A total of 806 consecutive patients with type 2 diabetes mellitus who were admitted to the diabetes center of Soonchunhyang University Hospital for blood glucose control were retrospectively reviewed. Patients with nephropathy were excluded. Subjects were categorized into quartiles of serum CysC levels (Q1, ≤0.65 mg/L; Q2, 0.66 to 0.79 mg/L; Q3, 0.80 to 0.94 mg/L; and Q4, ≥0.95 mg/L).

Results

The proportion of patients with diabetic retinopathy (DR) (P for trend <0.001), coronary heart disease (CHD) (P for trend <0.001), and stroke (P for trend <0.001) increased across the serum CysC quartiles. After adjustment for confounding factors, the highest serum CysC level remained a significant risk factor for DR (odds ratio [OR], 1.929; 95% confidence interval [CI], 1.007 to 4.144; P=0.040). Compared with Q1, a significant positive association was observed between serum CysC and CHD in Q2 (OR, 7.321; 95% CI, 1.114 to 48.114; P=0.012), Q3 (OR, 6.027; 95% CI, 0.952 to 38.161; P=0.020), and Q4 (OR, 8.122; 95% CI, 1.258 to 52.453; P=0.007). No associations were observed between CysC and stroke after additional adjustment for confounding variables.

Conclusion

Serum CysC levels are independently associated with DR and CHD, suggesting that CysC may be useful for identifying type 2 diabetes mellitus patients without nephropathy who are at high risk for vascular complications.

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Obesity and Metabolic Syndrome
Higher High Density Lipoprotein 2 (HDL2) to Total HDL Cholesterol Ratio Is Associated with a Lower Risk for Incident Hypertension: You-Cheol Hwang, Wilfred Y. Fujimoto, Steven E. Kahn, Donna L. Leonetti, Edward J. Boyko; Diabetes Metab J. 2019;43(1):114-122. Published online September 28, 2018; DOI: https://doi.org/10.4093/dmj.2018.0053

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Background

Recent studies have suggested that high density lipoprotein (HDL) cholesterol is inversely associated with the development of hypertension. We aimed to determine the association between different HDL cholesterol subclasses and risk of future hypertension.

Methods

A total of 270 Japanese Americans (130 men, 140 women) without hypertension between the ages of 34 to 75 years were enrolled. Blood pressure was measured with a mercury sphygmomanometer, and average blood pressure was calculated. Incident hypertension was determined 5 to 6 and 10 to 11 years after enrollment. HDL2, HDL3, and total HDL cholesterol were measured at baseline.

Results

During 10 years of follow-up, the cumulative incidence of hypertension was 28.1% (76/270). In univariate analysis, age, diabetes, waist circumference, systolic and diastolic blood pressure, fasting glucose, insulin resistance index, total and low density lipoprotein cholesterol, and visceral adipose tissue were significant predictors for incident hypertension. Among the HDL cholesterol subclass, HDL2 cholesterol was inversely associated with hypertension incidence, but both total and HDL3 cholesterol were not. In addition, HDL2/HDL cholesterol was inversely associated with future hypertension risk. In multivariate analysis, age (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26 to 2.31; P=0.001), systolic blood pressure (OR, 1.83; 95% CI, 1.31 to 2.56; P<0.001), and HDL2/HDL cholesterol (OR, 0.71; 95% CI, 0.52 to 0.98; P=0.035), were associated with future development of hypertension.

Conclusion

A higher proportion of HDL2 cholesterol among total HDL cholesterol predicted a lower risk for incident hypertension. However, concentrations of total HDL, HDL2, and HDL3 cholesterol were not independent predictors of incident hypertension.

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Complications
Cardiovascular Autonomic Neuropathy Predicts Higher HbA1c Variability in Subjects with Type 2 Diabetes Mellitus: Yeoree Yang, Eun-Young Lee, Jae-Hyoung Cho, Yong-Moon Park, Seung-Hyun Ko, Kun-Ho Yoon, Moo-Il Kang, Bong-Yun Cha, Seung-Hwan Lee; Diabetes Metab J. 2018;42(6):496-512. Published online September 28, 2018; DOI: https://doi.org/10.4093/dmj.2018.0026

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Background

This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus.

Methods

In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ≥6 measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements.

Results

A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (<7%).

Conclusion

CAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.

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Review

Complications
Diagnosing Diabetic Neuropathy: Something Old, Something New: Ioannis N. Petropoulos, Georgios Ponirakis, Adnan Khan, Hamad Almuhannadi, Hoda Gad, Rayaz A. Malik; Diabetes Metab J. 2018;42(4):255-269. Published online August 21, 2018; DOI: https://doi.org/10.4093/dmj.2018.0056

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There are potentially many ways of assessing diabetic peripheral neuropathy (DPN). However, they do not fulfill U.S. Food and Drug Administration (FDA) requirements in relation to their capacity to assess therapeutic benefit in clinical trials of DPN. Over the past several decades symptoms and signs, quantitative sensory and electrodiagnostic testing have been strongly endorsed, but have consistently failed as surrogate end points in clinical trials. Therefore, there is an unmet need for reliable biomarkers to capture the onset and progression and to facilitate drug discovery in DPN. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging modality for in vivo evaluation of sensory C-fibers. An increasing body of evidence from multiple centers worldwide suggests that CCM fulfills the FDA criteria as a surrogate endpoint of DPN.

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Sulwon Lecture 2017

Complications
The Role of Advanced Glycation End Products in Diabetic Vascular Complications: Sang Youl Rhee, Young Seol Kim; Diabetes Metab J. 2018;42(3):188-195. Published online May 31, 2018; DOI: https://doi.org/10.4093/dmj.2017.0105

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Abstract PDF PubReader ePub

In cases of chronic hyperglycemia, advanced glycation end-products (AGEs) are actively produced and accumulated in the circulating blood and various tissues. AGEs also accelerate the expression of receptors for AGEs, and they play an important role in the development of diabetic vascular complications through various mechanisms. Active interventions for glucose and related risk factors may help improve the clinical course of patients by reducing AGEs. This review summarizes recent updates on AGEs that have a significant impact on diabetic vascular complications.

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Brief Report

Others
Serum Soluble Epidermal Growth Factor Receptor Level Increase in Patients Newly Diagnosed with Type 2 Diabetes Mellitus: Ji Min Kim, Sorim Choung, Kyong Hye Joung, Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku; Diabetes Metab J. 2018;42(4):343-347. Published online May 2, 2018; DOI: https://doi.org/10.4093/dmj.2017.0082

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We analyzed circulating soluble epidermal growth factor receptor (sEGFR) levels in humans. Serum sEGFR levels were higher in subjects with newly diagnosed type 2 diabetes mellitus compared with controls. Serum sEGFR was positively correlated with glycosylated hemoglobin and serum glucose and negatively correlated with serum insulin and C-peptide levels.

Citations

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Type 2 diabetes mellitus and non-muscle invasive bladder cancer: characteristics of the epidermal growth factor system components content in blood, urine, and tumor
I. V. Kaplieva, E. M. Ataeva, E. M. Frantsiyants, L. K. Trepitaki, Yu. A. Petrova, A. N. Shewchenko, P. S. Kachesova, D. A. Shvyrev, S. G. Vlasov
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Increased serum extrachromosomal circular DNA SORBS1circle level is associated with insulin resistance in patients with newly diagnosed type 2 diabetes mellitus
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Effect of cholesterol-lowering agents on soluble epidermal growth factor receptor level in type 2 diabetes and hypercholesterolemia
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Original Articles

Epidemiology
Predictors of Incident Type 2 Diabetes Mellitus in Japanese Americans with Normal Fasting Glucose Level: You-Cheol Hwang, Wilfred Y. Fujimoto, Steven E. Kahn, Donna L. Leonetti, Edward J. Boyko; Diabetes Metab J. 2018;42(3):198-206. Published online April 25, 2018; DOI: https://doi.org/10.4093/dmj.2017.0100

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Background

Little is known about the natural course of normal fasting glucose (NFG) in Asians and the risk factors for future diabetes.

Methods

A total of 370 Japanese Americans (163 men, 207 women) with NFG levels and no history of diabetes, aged 34 to 75 years, were enrolled. Oral glucose tolerance tests were performed at baseline, 2.5, 5, and 10 years after enrollment.

Results

During 10 years of follow-up, 16.1% of participants met criteria for diabetes diagnosis, and 39.6% of subjects still had NFG levels at the time of diabetes diagnosis. During 5 years of follow-up, age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01 to 1.10; P=0.026) and family history of diabetes (OR, 3.24; 95% CI, 1.42 to 7.40; P=0.005) were independently associated with future diabetes diagnosis; however, fasting glucose level was not an independent predictor. During 10 years of follow-up, family history of diabetes (OR, 2.76; 95% CI, 1.37 to 5.54; P=0.004), fasting insulin level (OR, 1.01; 95% CI, 1.00 to 1.02; P=0.037), and fasting glucose level (OR, 3.69; 95% CI, 1.13 to 12.01; P=0.030) were associated with diabetes diagnosis independent of conventional risk factors for diabetes.

Conclusion

A substantial number of subjects with NFG at baseline still remained in the NFG range at the time of diabetes diagnosis. A family history of diabetes and fasting insulin and glucose levels were associated with diabetes diagnosis during 10 years of follow-up; however, fasting glucose level was not associated with diabetes risk within the relatively short-term follow-up period of 5 years in subjects with NFG.

Citations

Citations to this article as recorded by

Associations of the Gap Between 2-Hour Post-Load Plasma Glucose and Fasting Blood Glucose With All-Cause or Cardiovascular Mortality in US Normoglycemic Adults
Weiwei Liu, Zhiming Liu, Chen Ding, Jie Li, Haifeng Jiang
Biological Research For Nursing.2025; 27(3): 391. CrossRef
Continuous Glucose Monitoring Metrics in Asians Without Diabetes: Differentiating Prediabetes From Normoglycemia
Suresh Rama Chandran, Gerald Gui Ren Sng, Celine Yu Hui Wong, Wei Mian Ang, Daphne Gardner
Journal of Diabetes Science and Technology.2025;[Epub] CrossRef
J-shape relationship between normal fasting plasma glucose and risk of type 2 diabetes in the general population: results from two cohort studies
Linfeng He, Wenbin Zheng, Zeyu Li, Lu Chen, Wen Kong, Tianshu Zeng
Journal of Translational Medicine.2023;[Epub] CrossRef
Fasting plasma glucose and risk of type 2 diabetes mellitus in a group of Chinese people with normoglycemia and without obesity
Ziqiong Wang, Zheng Liu, Sen He
Journal of Diabetes.2021; 13(7): 601. CrossRef
Hidden Risks behind Normal Fasting Glucose: Is It Significant?
Seung-Hwan Lee
Diabetes & Metabolism Journal.2018; 42(3): 196. CrossRef

Obesity and Metabolic Syndrome
Air Pollution Has a Significant Negative Impact on Intentional Efforts to Lose Weight: A Global Scale Analysis: Morena Ustulin, So Young Park, Sang Ouk Chin, Suk Chon, Jeong-taek Woo, Sang Youl Rhee; Diabetes Metab J. 2018;42(4):320-329. Published online April 24, 2018; DOI: https://doi.org/10.4093/dmj.2017.0104

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Background

Air pollution causes many diseases and deaths. It is important to see how air pollution affects obesity, which is common worldwide. Therefore, we analyzed data from a smartphone application for intentional weight loss, and then we validated them.

Methods

Our analysis was structured in two parts. We analyzed data from a cohort registered to a smartphone application in 10 large cities of the world and matched it with the annual pollution values. We validated these results using daily pollution data in United States and matching them with user information. Body mass index (BMI) variation between final and initial login time was considered as outcome in the first part, and daily BMI in the validation. We analyzed: daily calories intake, daily weight, daily physical activity, geographical coordinates, seasons, age, gender. Weather Underground application programming interface provided daily climatic values. Annual and daily values of particulate matter PM10 and PM2.5 were extracted. In the first part of the analysis, we used 2,608 users and then 995 users located in United States.

Results

Air pollution was highest in Seoul and lowest in Detroit. Users decreased BMI by 2.14 kg/m² in average (95% confidence interval, −2.26 to −2.04). From a multilevel model, PM10 (β=0.04, P=0.002) and PM2.5 (β=0.08, P<0.001) had a significant negative effect on weight loss when collected per year. The results were confirmed with the validation (β_AQI*time=1.5×10^–5; P<0.001) by mixed effects model.

Conclusion

This is the first study that shows how air pollution affects intentional weight loss applied on wider area of the world.

Citations

Citations to this article as recorded by

A systematic review of evidence that environmental contaminant exposure impedes weight loss and glycemic control during calorie‐restricted diets in humans
Kimberley Ann Bennett, Calum Sutherland, Anne Louise Savage
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Review

Clinical Diabetes & Therapeutics
Past and Current Status of Adult Type 2 Diabetes Mellitus Management in Korea: A National Health Insurance Service Database Analysis: Seung-Hyun Ko, Kyungdo Han, Yong-ho Lee, Junghyun Noh, Cheol-Young Park, Dae-Jung Kim, Chang Hee Jung, Ki-Up Lee, Kyung-Soo Ko; Diabetes Metab J. 2018;42(2):93-100. Published online April 19, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.2.93

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Abstract PDF PubReader ePub

Korea's National Healthcare Program, the National Health Insurance Service (NHIS), a government-affiliated agency under the Korean Ministry of Health and Welfare, covers the entire Korean population. The NHIS supervises all medical services in Korea and establishes a systematic National Health Information database (DB). A health information DB system including all of the claims, medications, death information, and health check-ups, both in the general population and in patients with various diseases, is not common worldwide. On June 9, 2014, the NHIS signed a memorandum of understanding with the Korean Diabetes Association (KDA) to provide limited open access to its DB. By October 31, 2017, seven papers had been published through this collaborative research project. These studies were conducted to investigate the past and current status of type 2 diabetes mellitus and its complications and management in Korea. This review is a brief summary of the collaborative projects between the KDA and the NHIS over the last 3 years. According to the analysis, the national health check-up DB or claim DB were used, and the age category or study period were differentially applied.

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The Korean Journal of Medicine.2019; 94(5): 387. CrossRef
Second-line glucose-lowering drugs added to metformin and the risk of hospitalization for heart failure: A nationwide cohort study
Su Jin Lee, Kyoung Hwa Ha, Jung Hyun Lee, Hokyou Lee, Dae Jung Kim, Hyeon Chang Kim, Tatsuo Shimosawa
PLOS ONE.2019; 14(2): e0211959. CrossRef
2017 ACC/AHA Blood Pressure Classification and Cardiovascular Disease in 15 Million Adults of Age 20–94 Years
Hokyou Lee, So Mi Jemma Cho, Jong Heon Park, Sungha Park, Hyeon Chang Kim
Journal of Clinical Medicine.2019; 8(11): 1832. CrossRef
Management of Cardiovascular Risk Factors in Elderly Diabetes Mellitus Patients
Sung Hoon Yu
The Journal of Korean Diabetes.2019; 20(4): 233. CrossRef
Cholesterol levels and development of cardiovascular disease in Koreans with type 2 diabetes mellitus and without pre-existing cardiovascular disease
Mee Kyoung Kim, Kyungdo Han, Han Na Joung, Ki-Hyun Baek, Ki-Ho Song, Hyuk-Sang Kwon
Cardiovascular Diabetology.2019;[Epub] CrossRef
Comprehensive Efforts Are Needed to Improve the Quality of Primary Diabetes Care in Korea
Chan-Hee Jung
Endocrinology and Metabolism.2019; 34(3): 265. CrossRef
Blood Pressure and Development of Cardiovascular Disease in Koreans With Type 2 Diabetes Mellitus
Mee Kyoung Kim, Kyungdo Han, Eun Sil Koh, Eun Sook Kim, Min-Kyung Lee, Ga Eun Nam, Hyuk-Sang Kwon
Hypertension.2019; 73(2): 319. CrossRef
Weight change and mortality and cardiovascular outcomes in patients with new-onset diabetes mellitus: a nationwide cohort study
Mee Kyoung Kim, Kyungdo Han, Eun Sil Koh, Eun Sook Kim, Min-Kyung Lee, Ga Eun Nam, Hyuk-Sang Kwon
Cardiovascular Diabetology.2019;[Epub] CrossRef
Letter: Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J2019;43:582–9)
Tae Seo Sohn
Diabetes & Metabolism Journal.2019; 43(6): 909. CrossRef
Dipeptidyl Peptidase-4 Inhibitors versus Other Antidiabetic Drugs Added to Metformin Monotherapy in Diabetic Retinopathy Progression: A Real World-Based Cohort Study
Yoo-Ri Chung, Kyoung Hwa Ha, Hyeon Chang Kim, Sang Jun Park, Kihwang Lee, Dae Jung Kim
Diabetes & Metabolism Journal.2019; 43(5): 640. CrossRef
The Need to Improve the Quality of Diabetes Care in Korea
Seung Jin Han, Dae Jung Kim
Journal of Korean Medical Science.2019;[Epub] CrossRef
Chasms in Achievement of Recommended Diabetes Care among Geographic Regions in Korea
Sanghyun Cho, Ji-Yeon Shin, Hyun Joo Kim, Sang Jun Eun, Sungchan Kang, Won Mo Jang, Hyemin Jung, Yoon Kim, Jin Yong Lee
Journal of Korean Medical Science.2019;[Epub] CrossRef
An Age of Sodium-Glucose Cotransporter-2 Inhibitor Priority: Are We Ready?
Ji A Seo
Diabetes & Metabolism Journal.2019; 43(5): 578. CrossRef
National trends in metformin-based combination therapy of oral hypoglycaemic agents for type 2 diabetes mellitus
Jisu Kim, Susin Park, Hyunsoo Kim, Nam Kyung Je
European Journal of Clinical Pharmacology.2019; 75(12): 1723. CrossRef
HDL-Cholesterol, Its Variability, and the Risk of Diabetes: A Nationwide Population-Based Study
Seung-Hwan Lee, Hun-Sung Kim, Yong-Moon Park, Hyuk-Sang Kwon, Kun-Ho Yoon, Kyungdo Han, Mee Kyoung Kim
The Journal of Clinical Endocrinology & Metabolism.2019; 104(11): 5633. CrossRef
Current Management of Type 2 Diabetes Mellitus in Primary Care Clinics in Korea
Da Hea Seo, Shinae Kang, Yong-ho Lee, Jung Yoon Ha, Jong Suk Park, Byoung-Wan Lee, Eun Seok Kang, Chul Woo Ahn, Bong-Soo Cha
Endocrinology and Metabolism.2019; 34(3): 282. CrossRef
Heritability estimation of dichotomous phenotypes using a liability threshold model on ascertained family‐based samples
Wonji Kim, Soo Heon Kwak, Sungho Won
Genetic Epidemiology.2019; 43(7): 761. CrossRef
Letter: Dipeptidyl Peptidase-4 Inhibitors versus Other Antidiabetic Drugs Added to Metformin Monotherapy in Diabetic Retinopathy Progression: A Real World-Based Cohort Study (Diabetes Metab J 2019;43:640–8)
Jun Sung Moon
Diabetes & Metabolism Journal.2019; 43(6): 911. CrossRef
Association of Obstructive Sleep Apnea With the Risk of Ménière’s Disease and Sudden Sensorineural Hearing Loss: A Study Using Data From the Korean National Health Insurance Service
Jong-Yeup Kim, Inseok Ko, Bum-Joo Cho, Dong-Kyu Kim
Journal of Clinical Sleep Medicine.2019; 15(9): 1293. CrossRef

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