Endocrinology and Metabolism

Review Articles

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database: Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee; Endocrinol Metab. 2023;38(1):10-24. Published online February 9, 2023; DOI: https://doi.org/10.3803/EnM.2023.102

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The Korean National Health Information Database (NHID) contains big data combining information obtained from the National Health Insurance Service and health examinations. Data are provided in the form of a cohort, and the NHID can be used to conduct longitudinal studies and research on rare diseases. Moreover, data on the cause and date of death are provided by Statistics Korea. Research and publications based on the NHID have increased explosively in the field of endocrine disorders. However, because the data were not collected for research purposes, studies using the NHID have limitations, particularly the need for the operational definition of diseases. In this review, we describe the characteristics of the Korean NHID, operational definitions of endocrine diseases used for research, and an overview of recent studies in endocrinology using the Korean NHID.

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Different Associations between Lipid Levels and Risk for Heart Failure according to Diabetes Progression
Seung-Hwan Lee, Kyu Na Lee, Jong-Chan Youn, Hun Sung Kim, Kyungdo Han, Mee Kyoung Kim
Diabetes & Metabolism Journal.2025; 49(1): 105. CrossRef
Diabetes Fact Sheets in Korea 2024
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Diabetes & Metabolism Journal.2025; 49(1): 24. CrossRef
Big Data Research for Diabetes-Related Diseases Using the Korean National Health Information Database
Kyung-Soo Kim, Bongseong Kim, Kyungdo Han
Diabetes & Metabolism Journal.2025; 49(1): 13. CrossRef
Reflections on the 2024 KTA Guideline and the Role of Radioiodine Therapy in Differentiated Thyroid Cancer
Minseok Suh, So Won Oh, Gi Jeong Cheon, June-Key Chung
Nuclear Medicine and Molecular Imaging.2025; 59(2): 95. CrossRef
Effects of Pancreatitis and Type 2 Diabetes Mellitus on the Development of Pancreatic Cancer: A Nationwide Nested Case-Control Study
Young-eun Kim, Min Heui Yu, Chung Mo Nam, Eun Seok Kang
Diabetes & Metabolism Journal.2025; 49(2): 252. CrossRef
Prevalence, Incidence, and Metabolic Characteristics of Young Adults with Type 2 Diabetes Mellitus in South Korea (2010–2020)
Ji Yoon Kim, Jiyoon Lee, Joon Ho Moon, Se Eun Park, Seung-Hyun Ko, Sung Hee Choi, Nam Hoon Kim
Diabetes & Metabolism Journal.2025; 49(2): 172. CrossRef
Association between glycaemic status and the risk of acromegaly: a nationwide population-based cohort study
Eun Roh, Ji Hye Heo, Han Na Jung, Kyung Do Han, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm
BMJ Open.2025; 15(3): e087884. CrossRef
Associations Between Physical Activity and the Risk of Hip Fracture Depending on Glycemic Status: A Nationwide Cohort Study
Kyoung Min Kim, Kyoung Jin Kim, Kyungdo Han, Yumie Rhee
The Journal of Clinical Endocrinology & Metabolism.2024; 109(3): e1194. CrossRef
Weight change in patients with new‐onset type 2 diabetes mellitus and its association with remission: Comprehensive real‐world data
Jinyoung Kim, Bongseong Kim, Mee Kyoung Kim, Ki‐Hyun Baek, Ki‐Ho Song, Kyungdo Han, Hyuk‐Sang Kwon
Diabetes, Obesity and Metabolism.2024; 26(2): 567. CrossRef
Diabetes severity and the risk of depression: A nationwide population-based study
Yunjung Cho, Bongsung Kim, Hyuk-Sang Kwon, Kyungdo Han, Mee Kyoung Kim
Journal of Affective Disorders.2024; 351: 694. CrossRef
Information Bias Might Exaggerate Lung Cancer Risk of Patients With Rheumatoid Arthritis
Nobuyuki Horita, Kaoru Takase-Minegishi
Journal of Thoracic Oncology.2024; 19(2): 348. CrossRef
Diabetes Duration, Cholesterol Levels, and Risk of Cardiovascular Diseases in Individuals With Type 2 Diabetes
Mee Kyoung Kim, Kyu Na Lee, Kyungdo Han, Seung-Hwan Lee
The Journal of Clinical Endocrinology & Metabolism.2024; 109(12): e2317. CrossRef
Risk of fracture in patients with myasthenia gravis: a nationwide cohort study in Korea
Hye-Sun Park, Kyoungsu Kim, Min Heui Yu, Ha Young Shin, Yumie Rhee, Seung Woo Kim, Namki Hong
Journal of Bone and Mineral Research.2024; 39(6): 688. CrossRef
All-cause and cause-specific mortality risks in individuals with diabetes living alone: A large-scale population-based cohort study
Jae-Seung Yun, Kyungdo Han, Bongseong Kim, Seung-Hyun Ko, Hyuk-Sang Kwon, Yu-Bae Ahn, Yong-Moon Mark Park, Seung-Hwan Lee
Diabetes Research and Clinical Practice.2024; 217: 111876. CrossRef
Epidemiology and Trends of Obesity and Bariatric Surgery in Korea
Kyungdo Han, Jin-Hyung Jung, Su-Min Jeong, Mee Kyoung Kim
Endocrinology and Metabolism.2024; 39(5): 678. CrossRef
Income-Related Disparities in Mortality Among Young Adults With Type 2 Diabetes
Ji Yoon Kim, Sojeong Park, Minae Park, Nam Hoon Kim, Sin Gon Kim
JAMA Network Open.2024; 7(11): e2443918. CrossRef
Effect of COVID-19 Vaccination on Thyroid Disease in 7 Million Adult and 0.2 Million Adolescent Vaccine Recipients
Sungho Bea, Hwa Young Ahn, Jieun Woo, Ju-Young Shin, Sun Wook Cho
The Journal of Clinical Endocrinology & Metabolism.2024;[Epub] CrossRef
Diabetes severity is strongly associated with the risk of active tuberculosis in people with type 2 diabetes: a nationwide cohort study with a 6-year follow-up
Ji Young Kang, Kyungdo Han, Seung-Hwan Lee, Mee Kyoung Kim
Respiratory Research.2023;[Epub] CrossRef
Research on obesity using the National Health Information Database: recent trends
Eun-Jung Rhee
Cardiovascular Prevention and Pharmacotherapy.2023; 5(2): 35. CrossRef
Pituitary Diseases and COVID-19 Outcomes in South Korea: A Nationwide Cohort Study
Jeonghoon Ha, Kyoung Min Kim, Dong-Jun Lim, Keeho Song, Gi Hyeon Seo
Journal of Clinical Medicine.2023; 12(14): 4799. CrossRef
Risk of Pancreatic Cancer and Use of Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matching Analysis
Mee Kyoung Kim, Kyungdo Han, Hyuk-Sang Kwon, Soon Jib Yoo
Endocrinology and Metabolism.2023; 38(4): 426. CrossRef
Prevalence, Treatment Status, and Comorbidities of Hyperthyroidism in Korea from 2003 to 2018: A Nationwide Population Study
Hwa Young Ahn, Sun Wook Cho, Mi Young Lee, Young Joo Park, Bon Seok Koo, Hang-Seok Chang, Ka Hee Yi
Endocrinology and Metabolism.2023; 38(4): 436. CrossRef
Is Thyroid Dysfunction Associated with Unruptured Intracranial Aneurysms? A Population-Based, Nested Case–Control Study from Korea
Hyeree Park, Sun Wook Cho, Sung Ho Lee, Kangmin Kim, Hyun-Seung Kang, Jeong Eun Kim, Aesun Shin, Won-Sang Cho
Thyroid®.2023; 33(12): 1483. CrossRef
Risk of Cause-Specific Mortality across Glucose Spectrum in Elderly People: A Nationwide Population-Based Cohort Study
Joonyub Lee, Hun-Sung Kim, Kee-Ho Song, Soon Jib Yoo, Kyungdo Han, Seung-Hwan Lee
Endocrinology and Metabolism.2023; 38(5): 525. CrossRef
Risk of depression in patients with acromegaly in Korea (2006-2016): a nationwide population-based study
Shinje Moon, Sangmo Hong, Kyungdo Han, Cheol-Young Park
European Journal of Endocrinology.2023; 189(3): 363. CrossRef
Cumulative effect of impaired fasting glucose on the risk of dementia in middle-aged and elderly people: a nationwide cohort study
Jin Yu, Kyu-Na Lee, Hun-Sung Kim, Kyungdo Han, Seung-Hwan Lee
Scientific Reports.2023;[Epub] CrossRef
Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study
Han-Sang Baek, Bongseong Kim, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Sang-Ah Chang, Kyungdo Han, Jae-Seung Yun
Endocrinology and Metabolism.2023; 38(6): 770. CrossRef
Increased Risk of Hip Fracture in Patients with Acromegaly: A Nationwide Cohort Study in Korea
Jiwon Kim, Namki Hong, Jimi Choi, Ju Hyung Moon, Eui Hyun Kim, Eun Jig Lee, Sin Gon Kim, Cheol Ryong Ku
Endocrinology and Metabolism.2023; 38(6): 690. CrossRef

Diabetes, Obesity and Metabolism
Renal Protection of Mineralocorticoid Receptor Antagonist, Finerenone, in Diabetic Kidney Disease: Dong-Lim Kim, Seung-Eun Lee, Nan Hee Kim; Endocrinol Metab. 2023;38(1):43-55. Published online February 27, 2023; DOI: https://doi.org/10.3803/EnM.2022.1629

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Chronic kidney disease (CKD) is the most common cause of end-stage renal disease in patients with type 2 diabetes mellitus (T2DM). CKD increases the risk of cardiovascular diseases; therefore, its prevention and treatment are important. The prevention of diabetic kidney disease (DKD) can be achieved through intensive glycemic control and blood pressure management. Additionally, DKD treatment aims to reduce albuminuria and improve kidney function. In patients with T2DM, renin-angiotensin-aldosterone system inhibitors, sodium glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists can delay the progression of DKD. Hence, there is a need for novel treatments that can effectively suppress DKD progression. Finerenone is a first-in-class nonsteroidal mineralocorticoid receptor antagonist with clinically proven efficacy in improving albuminuria, estimated glomerular filtration rate, and risk of cardiovascular events in early and advanced DKD. Therefore, finerenone is a promising treatment option to delay DKD progression. This article reviews the mechanism of renal effects and major clinical outcomes of finerenone in DKD.

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Finerenona no Tratamento da Nefropatia Diabética: Perspectivas Atuais e Evidências Clínicas
Rosana Maciel Schmidt, Luis Alberto Batista Peres, Alfredo Casagrande Laude
Cuadernos de Educación y Desarrollo.2025; 17(3): e7760. CrossRef
Role and application prospective of non-steroidal MRA in the treatment of diabetic kidney disease
Yu Sun, Mingzhu Wang
International Urology and Nephrology.2025;[Epub] CrossRef
Distinct Roles of Common Genetic Variants and Their Contributions to Diabetes: MODY and Uncontrolled T2DM
Shadi Bazzazzadehgan, Zia Shariat-Madar, Fakhri Mahdi
Biomolecules.2025; 15(3): 414. CrossRef
Renal function trajectories of Japanese adults with diabetic kidney disease on different diet therapies including energy-restricted and low-carbohydrate diets: a retrospective cohort study
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Neue Antihypertensiva im Renin-Angiotensin-Aldosteron-System
Markus van der Giet
CardioVasc.2024; 24(1): 33. CrossRef
Chicoric acid advanced PAQR3 ubiquitination to ameliorate ferroptosis in diabetes nephropathy through the relieving of the interaction between PAQR3 and P110α pathway
Weiwei Zhang, Yong Liu, Jiajun Zhou, Teng Qiu, Haitang Xie, Zhichen Pu
Clinical and Experimental Hypertension.2024;[Epub] CrossRef
Endothelial CXCR2 deficiency attenuates renal inflammation and glycocalyx shedding through NF-κB signaling in diabetic kidney disease
Siyuan Cui, Xin Chen, Jiayu Li, Wei Wang, Deqi Meng, Shenglong Zhu, Shiwei Shen
Cell Communication and Signaling.2024;[Epub] CrossRef
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection
Alessio Mazzieri, Francesca Porcellati, Francesca Timio, Gianpaolo Reboldi
International Journal of Molecular Sciences.2024; 25(7): 3969. CrossRef
Rediscovery of the implication of albuminuria in heart failure: emerging classic index for cardiorenal interaction
Kyung‐Duk Min, Yuki Matsumoto, Masanori Asakura, Masaharu Ishihara
ESC Heart Failure.2024; 11(6): 3470. CrossRef
Decoding the role of aldosterone in glycation-induced diabetic complications
Mayura Apte, Saee Zambre, Pratiksha Pisar, Bishnudeo Roy, Rashmi Tupe
Biochemical and Biophysical Research Communications.2024; 721: 150107. CrossRef
Exploring the potential of finerenone in non-diabetic chronic kidney disease: a promising frontier
Ayesha Maryam, Muhammad Salman Nadeem, Ayesha Fatima, Kashaf Noor Asmat
International Urology and Nephrology.2024; 57(1): 295. CrossRef
A new perspective on proteinuria and drug therapy for diabetic kidney disease
Ruimin Zhang, Qian Wang, Yaqing Li, Qihu Li, Xuefeng Zhou, Xiangmei Chen, Zheyi Dong
Frontiers in Pharmacology.2024;[Epub] CrossRef
Molecular Therapeutics for Diabetic Kidney Disease: An Update
Man Guo, Fangfang He, Chun Zhang
International Journal of Molecular Sciences.2024; 25(18): 10051. CrossRef
Pharmacokinetic and Pharmacodynamic Interaction of Finerenone with Diltiazem, Fluconazole, and Ritonavir in Rats
Tham Thi Bui, So-Hyeon Kim, Woojin Jung, Sung-yoon Yang, Quyen Thi Tran, Hyunjung Lee, Seongwon Park, Lien Thi Ngo, Hwi-yeol Yun, Jung-woo CHAE
European Journal of Drug Metabolism and Pharmacokinetics.2024; 49(6): 701. CrossRef
A comprehensive review of finerenone—a third-generation non-steroidal mineralocorticoid receptor antagonist
Shuhui Zhai, Baisheng Ma, Weiwei Chen, Qini Zhao
Frontiers in Cardiovascular Medicine.2024;[Epub] CrossRef
Exercise as a therapeutic approach to alleviate diabetic kidney disease: mechanisms, clinical evidence and potential exercise prescriptions
Rao Fan, Jianda Kong, Jiahao Zhang, Lei Zhu
Frontiers in Medicine.2024;[Epub] CrossRef
Omics Studies in CKD: Diagnostic Opportunities and Therapeutic Potential
Merita Rroji, Goce Spasovski
PROTEOMICS.2024;[Epub] CrossRef
Aldosterone Synthase Inhibitors for Cardiorenal Protection: Ready for Prime Time?
Alessio Mazzieri, Francesca Timio, Francesco Patera, Francesco Trepiccione, Mario Bonomini, Gianpaolo Reboldi
Kidney and Blood Pressure Research.2024; 49(1): 1041. CrossRef
Finerenone: a breakthrough mineralocorticoid receptor antagonist for heart failure, diabetes and chronic kidney disease
Akshyaya Pradhan, Umesh Chandra Tripathi
The Egyptian Heart Journal.2024;[Epub] CrossRef
Epigenetic modification in diabetic kidney disease
Zhe Liu, Jiahui Liu, Wanning Wang, Xingna An, Ling Luo, Dehai Yu, Weixia Sun
Frontiers in Endocrinology.2023;[Epub] CrossRef
Novel Approaches in Chronic Renal Failure without Renal Replacement Therapy: A Review
Sandra Martínez-Hernández, Martín Muñoz-Ortega, Manuel Ávila-Blanco, Mariana Medina-Pizaño, Javier Ventura-Juárez
Biomedicines.2023; 11(10): 2828. CrossRef
Finerenone and other future therapeutic options for Alport syndrome
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Journal of Rare Diseases.2023;[Epub] CrossRef

Original Article

Diabetes, obesity and metabolism
Triglyceride-Glucose Index Predicts Future Atherosclerotic Cardiovascular Diseases: A 16-Year Follow-up in a Prospective, Community-Dwelling Cohort Study: Joon Ho Moon, Yongkang Kim, Tae Jung Oh, Jae Hoon Moon, Soo Heon Kwak, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi, Nam H. Cho; Endocrinol Metab. 2023;38(4):406-417. Published online August 3, 2023; DOI: https://doi.org/10.3803/EnM.2023.1703

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Background
While the triglyceride-glucose (TyG) index is a measure of insulin resistance, its association with cardiovascular disease (CVD) has not been well elucidated. We evaluated the TyG index for prediction of CVDs in a prospective large communitybased cohort.
Methods
Individuals 40 to 70 years old were prospectively followed for a median 15.6 years. The TyG index was calculated as the Ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. CVDs included any acute myocardial infarction, coronary artery disease or cerebrovascular disease. We used a Cox proportional hazards model to estimate CVD risks according to quartiles of the TyG index and plotted the receiver operating characteristics curve for the incident CVD.
Results
Among 8,511 subjects (age 51.9±8.8 years; 47.5% males), 931 (10.9%) had incident CVDs during the follow-up. After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, total cholesterol, smoking, alcohol, exercise, and C-reactive protein, subjects in the highest TyG quartile had 36% increased risk of incident CVD compared with the lowest TyG quartile (hazard ratio, 1.36; 95% confidence interval, 1.10 to 1.68). Carotid plaque, assessed by ultrasonography was more frequent in subjects in the higher quartile of TyG index (P for trend=0.049 in men and P for trend <0.001 in women). The TyG index had a higher predictive power for CVDs than the homeostasis model assessment of insulin resistance (HOMA-IR) (area under the curve, 0.578 for TyG and 0.543 for HOMA-IR). Adding TyG index on diabetes or hypertension alone gave sounder predictability for CVDs.
Conclusion
The TyG index is independently associated with future CVDs in 16 years of follow-up in large, prospective Korean cohort.

Citations

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Elevated triglyceride-glucose index as a predictor of carotid plaque incidence: Insights from a comprehensive meta-analysis
Arankesh Mahadevan, Bhavin A. Patel, Sashwath Srikanth, Raja Godasi, Rupak Desai
The American Journal of the Medical Sciences.2025; 369(2): 197. CrossRef
Analysis of the correlation between the serum triglyceride glucose index and the risk of death in patients on maintenance hemodialysis: a retrospective cohort study
Xiaokeng Chi, Shuxin Chen, Zhe Huang, Rong Zhou, Zhicheng Su, Qiujun Mai, Yilin Xu, Jianxin Wan
PeerJ.2025; 13: e18781. CrossRef
Assessing the predictive value of elevated triglycerides, triglyceride-glucose index (TyG), and TG/HDL ratios for cardiovascular disease and mortality during 20 years of follow-up: Tehran lipid and glucose study
Shayesteh Khalili, Atieh Amouzegar, Seyed Sattar Dorost, Fereidoun Azizi, Aryan Salahi-Niri
Clinical Biochemistry.2025; 136: 110891. CrossRef
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Haoyue Cao, Qinglin Li, Juxiang Yuan
Scientific Reports.2025;[Epub] CrossRef
Association between the triglyceride-glucose index and silent myocardial infarction in the general population
Min Dai, Dongze Li, Jing Yu, Yi Liu, Qin Zhang, Wei Zhang, Yan Zhong, Zhi Wan, Menglin Tang, Yongli Gao, Li Rao
Scientific Reports.2025;[Epub] CrossRef
Integrative Multi‐Omics and Routine Blood Analysis Using Deep Learning: Cost‐Effective Early Prediction of Chronic Disease Risks
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Advanced Science.2025;[Epub] CrossRef
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So Hyun Cho, Gyuri Kim, Kyu-na Lee, Rosa Oh, Ji Yoon Kim, Myunghwa Jang, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Kyungdo Han, Jae Hyeon Kim
Scientific Reports.2025;[Epub] CrossRef
Construction and validation of a nomogram for predicting diabetes remission at 3 months after bariatric surgery in patients with obesity combined with type 2 diabetes mellitus
Kaisheng Yuan, Bing Wu, Ruiqi Zeng, Fuqing Zhou, Ruixiang Hu, Cunchuan Wang
Diabetes, Obesity and Metabolism.2024; 26(1): 169. CrossRef
Association between the triglyceride glucose index and chronic total coronary occlusion: A cross-sectional study from southwest China
Kaiyong Xiao, Huili Cao, Bin Yang, Zhe Xv, Lian Xiao, Jianping Wang, Shuiqing Ni, Hui Feng, Zhongwei He, Lei Xv, Juan Li, Dongmei Xv
Nutrition, Metabolism and Cardiovascular Diseases.2024; 34(4): 850. CrossRef
The association between TyG and all-cause/non-cardiovascular mortality in general patients with type 2 diabetes mellitus is modified by age: results from the cohort study of NHANES 1999–2018
Younan Yao, Bo Wang, Tian Geng, Jiyan Chen, Wan Chen, Liwen Li
Cardiovascular Diabetology.2024;[Epub] CrossRef
Comparison of triglyceride glucose index and modified triglyceride glucose indices in prediction of cardiovascular diseases in middle aged and older Chinese adults
Cancan Cui, Yitian Qi, Jiayin Song, Xinyun Shang, Tianjiao Han, Ning Han, Siqi Yue, Yining Zha, Zhonghang Xu, Jiannan Li, Lin Liu
Cardiovascular Diabetology.2024;[Epub] CrossRef
Triglyceride-glucose index predicts type 2 diabetes mellitus more effectively than oral glucose tolerance test-derived insulin sensitivity and secretion markers
Min Jin Lee, Ji Hyun Bae, Ah Reum Khang, Dongwon Yi, Mi Sook Yun, Yang Ho Kang
Diabetes Research and Clinical Practice.2024; 210: 111640. CrossRef
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Tolga Han Efe, Engin Algül
Biomarkers in Medicine.2024; 18(6): 243. CrossRef
Triglyceride-Glucose Index as Predictor for Hypertension, CHD and STROKE Risk among Non-Diabetic Patients: A NHANES Cross-Sectional Study 2001–2020
Bisher Sawaf, Sarya Swed, Hidar Alibrahim, Haidara Bohsas, Tirth Dave, Mohamad Nour Nasif, Wael Hafez, Fatema Ali Asgar Tashrifwala, Yazan Khair Eldien Jabban, Safwan Al-Rassas, Heba haj Saleh, Abdul Rehman Zia Zaidi, Baraa Alghalyini, Shaymaa Abdelmaboud
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An Increasing Triglyceride–Glucose Index Is Associated with a Pro-Inflammatory and Pro-Oxidant Phenotype
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Inflammatory and Metabolic Predictors of Mortality in Pulmonary Thromboembolism: A Focus on the Triglyceride–Glucose Index and Pan-Immune Inflammation Value
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Verena Gounden, Sridevi Devaraj, Ishwarlal Jialal
Lipids in Health and Disease.2024;[Epub] CrossRef
Evaluation of the novel three lipid indices for predicting five- and ten-year incidence of cardiovascular disease: findings from Kerman coronary artery disease risk factors study (KERCADRS)
Alireza Jafari, Hamid Najafipour, Mitra Shadkam, Sina Aminizadeh
Lipids in Health and Disease.2023;[Epub] CrossRef

Review Article

Diabetes, obesity and metabolism
The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update: Agnieszka Jakubowska, Carel W. le Roux, Adie Viljoen; Endocrinol Metab. 2024;39(1):12-22. Published online February 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.1942

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Obesity is the fifth leading risk factor for global deaths with numbers continuing to increase worldwide. In the last 20 years, the emergence of pharmacological treatments for obesity based on gastrointestinal hormones has transformed the therapeutic landscape. The successful development of glucagon-like peptide-1 (GLP-1) receptor agonists, followed by the synergistic combined effect of glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists achieved remarkable weight loss and glycemic control in those with the diseases of obesity and type 2 diabetes. The multiple cardiometabolic benefits include improving glycemic control, lipid profiles, blood pressure, inflammation, and hepatic steatosis. The 2023 phase 2 double-blind, randomized controlled trial evaluating a GLP-1/GIP/glucagon receptor triagonist (retatrutide) in patients with the disease of obesity reported 24.2% weight loss at 48 weeks with 12 mg retatrutide. This review evaluates the current available evidence for GLP-1 receptor agonists, dual GLP-1/GIP receptor co-agonists with a focus on GLP-1/GIP/glucagon receptor triagonists and discusses the potential future benefits and research directions.

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New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review
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Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, anti-diabetic drugs in heart failure and cognitive impairment: potential mechanisms of the protective effects
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Mechanisms of Glucagon Receptor Agonism and GLP-1/Glucagon/GIP Receptor Triple Agonism for Treatment of Diabetes and Obesity
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Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide
Wenzhuo Li, Qingtong Zhou, Zhaotong Cong, Qingning Yuan, Wenxin Li, Fenghui Zhao, H. Eric Xu, Li-Hua Zhao, Dehua Yang, Ming-Wei Wang
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Original Articles

Diabetes, obesity and metabolism
Efficacy and Safety of Omarigliptin, a Novel Once-Weekly Dipeptidyl Peptidase-4 Inhibitor, in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis: A.B.M. Kamrul-Hasan, Muhammad Shah Alam, Samir Kumar Talukder, Deep Dutta, Shahjada Selim; Endocrinol Metab. 2024;39(1):109-126. Published online January 23, 2024; DOI: https://doi.org/10.3803/EnM.2023.1839

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Background
No recent meta-analysis has holistically analyzed and summarized the efficacy and safety of omarigliptin in type 2 diabetes mellitus (T2DM). We conducted a meta-analysis to address this knowledge gap.
Methods
Electronic databases were searched to identify randomized controlled trials (RCTs) that included patients with T2DM who received omarigliptin in the intervention arm. The control arm consisted of either a placebo (passive control group [PCG]) or an active comparator (active control group [ACG]). The primary outcome assessed was changes in hemoglobin A1c (HbA1c), while secondary outcomes included variations in glucose levels, achievement of glycemic targets, adverse events (AEs), and hypoglycemic events.
Results
From 332 initially screened articles, data from 16 RCTs involving 8,804 subjects were analyzed. Omarigliptin demonstrated superiority over placebo in reducing HbA1c levels (mean difference, –0.58%; 95% confidence interval, –0.75 to –0.40; P<0.00001; I²=91%). Additionally, omarigliptin outperformed placebo in lowering fasting plasma glucose, 2-hour postprandial glucose, and in the percentage of participants achieving HbA1c levels below 7.0% and 6.5%. The glycemic efficacy of omarigliptin was similar to that of the ACG across all measures. Although the omarigliptin group experienced a higher incidence of hypoglycemic events compared to the PCG, the overall AEs, serious AEs, hypoglycemia, and severe hypoglycemia were comparable between the omarigliptin and control groups (PCG and ACG).
Conclusion
Omarigliptin has a favorable glycemic efficacy and safety profile for managing T2DM.

Citations

Citations to this article as recorded by

Once-Weekly Tirzepatide Versus Once-Daily Basal Insulin in Managing Type 2 Diabetes Inadequately Controlled With Oral anti-Hyperglycemic Drugs: A Systematic Review and Meta-Analysis
A.B.M. Kamrul-Hasan, Shahjada Selim, Faria Afsana, Lakshmi Nagendra, Rezwana Ahmed, Deep Dutta
Endocrine Practice.2025; 31(3): 315. CrossRef
Renal effects and safety of tirzepatide in subjects with and without diabetes: A systematic review and meta-analysis
A B M Kamrul-Hasan, Shinjan Patra, Deep Dutta, Lakshmi Nagendra, AFM Muntahi-Reza, Sanja Borozan, Joseph M Pappachan
World Journal of Diabetes.2025;[Epub] CrossRef
Tirzepatide and Cancer Risk in Individuals with and without Diabetes: A Systematic Review and Meta-Analysis
A.B.M. Kamrul-Hasan, Muhammad Shah Alam, Deep Dutta, Thanikai Sasikanth, Fatema Tuz Zahura Aalpona, Lakshmi Nagendra
Endocrinology and Metabolism.2025; 40(1): 112. CrossRef
Reasons for discontinuing tirzepatide in randomized controlled trials: A systematic review and meta-analysis
Abul Bashar Mohammad Kamrul-Hasan, Joseph M Pappachan, Deep Dutta, Lakshmi Nagendra, Mohammad Shafi Kuchay, Nitin Kapoor
World Journal of Diabetes.2025;[Epub] CrossRef
Role of flibanserin in managing hypoactive sexual desire disorder in women: A systematic review and meta-analysis
A.B.M. Kamrul-Hasan, Mohammad Abdul Hannan, Muhammad Shah Alam, Fatema Tuz Zahura Aalpona, Lakshmi Nagendra, Shahjada Selim, Deep Dutta
Medicine.2024; 103(25): e38592. CrossRef
Teneligliptin: A potential therapeutic approach for diabetic cardiomyopathy
Ashraf Al Madhoun
World Journal of Diabetes.2024; 15(8): 1654. CrossRef
Inhibition of Oxidative Stress and Related Signaling Pathways in Neuroprotection
Maja Jazvinšćak Jembrek
Antioxidants.2024; 13(9): 1033. CrossRef
Safety and Efficacy of the Novel RNA Interference Therapies for Hypertriglyceridemia and Mixed Hyperlipidemia Management: A Systematic Review and Meta-analysis
A.B.M. Kamrul-Hasan, Deep Dutta, Lakshmi Nagendra, Sunetra Mondal, Saptarshi Bhattacharya, Sanjay Kalra
Endocrine Practice.2024; 30(11): 1103. CrossRef
Hepatobiliary effects and safety of tirzepatide: A systematic review and meta‐analysis
A. B. M. Kamrul‐Hasan, Deep Dutta, Lakshmi Nagendra, Mohammad Shafi Kuchay, Md. Saiful Islam, Joseph M. Pappachan
Diabetes, Obesity and Metabolism.2024; 26(12): 6074. CrossRef
Efficacy and Safety of Ertugliflozin Compared to Placebo in Patients With Type 2 Diabetes: An Updated Systematic Review and Meta‐Analysis
A. B. M. Kamrul-Hasan, Muhammad Shah Alam, Samir Kumar Talukder, Mohammad Abdul Hannan, Deep Dutta, Lakshmi Nagendra, Shahjada Selim, Eusebio Chiefari
Journal of Diabetes Research.2024;[Epub] CrossRef
Optimal Use of Once-Weekly Basal Insulin Efsitora Alfa in Type 1 and Type 2 Diabetes: A Systematic Review and Meta-Analysis
Deep Dutta, Lakshmi Nagendra, Manoj Kumar, A.B.M. Kamrul-Hasan, Saptarshi Bhattacharya
Endocrine Practice.2024;[Epub] CrossRef
Neuropsychiatric Effects of Tirzepatide: A Systematic Review and Meta-Analysis
A.B.M. Kamrul-Hasan, Sanja Borozan, Deep Dutta, Lakshmi Nagendra, Dina Shrestha, Joseph M. Pappachan
Endocrine Practice.2024;[Epub] CrossRef
Pancreatic Safety of Tirzepatide and Its Effects on Islet Cell Function: A Systematic Review and Meta‐Analysis
A. B. M. Kamrul‐Hasan, Sunetra Mondal, Deep Dutta, Lakshmi Nagendra, Mohammed Ruhul Kabir, Joseph M. Pappachan
Obesity Science & Practice.2024;[Epub] CrossRef

Diabetes, obesity and metabolism
Inhibition of Fatty Acid β-Oxidation by Fatty Acid Binding Protein 4 Induces Ferroptosis in HK2 Cells Under High Glucose Conditions: Jiasi Chen, Keping Wu, Yan Lei, Mingcheng Huang, Lokyu Cheng, Hui Guan, Jiawen Lin, Ming Zhong, Xiaohua Wang, Zhihua Zheng; Endocrinol Metab. 2023;38(2):226-244. Published online April 27, 2023; DOI: https://doi.org/10.3803/EnM.2022.1604

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Background
Ferroptosis, which is caused by an iron-dependent accumulation of lipid hydroperoxides, is a type of cell death linked to diabetic kidney disease (DKD). Previous research has shown that fatty acid binding protein 4 (FABP4) is involved in the regulation of ferroptosis in diabetic retinopathy. The present study was constructed to explore the role of FABP4 in the regulation of ferroptosis in DKD.
Methods
We first detected the expression of FABP4 and proteins related to ferroptosis in renal biopsies of patients with DKD. Then, we used a FABP4 inhibitor and small interfering RNA to investigate the role of FABP4 in ferroptosis induced by high glucose in human renal proximal tubular epithelial (HG-HK2) cells.
Results
In kidney biopsies of DKD patients, the expression of FABP4 was elevated, whereas carnitine palmitoyltransferase-1A (CP-T1A), glutathione peroxidase 4, ferritin heavy chain, and ferritin light chain showed reduced expression. In HG-HK2 cells, the induction of ferroptosis was accompanied by an increase in FABP4. Inhibition of FABP4 in HG-HK2 cells changed the redox state, sup-pressing the production of reactive oxygen species, ferrous iron (Fe²⁺), and malondialdehyde, increasing superoxide dismutase, and reversing ferroptosis-associated mitochondrial damage. The inhibition of FABP4 also increased the expression of CPT1A, reversed lipid deposition, and restored impaired fatty acid β-oxidation. In addition, the inhibition of CPT1A could induce ferroptosis in HK2 cells.
Conclusion
Our results suggest that FABP4 mediates ferroptosis in HG-HK2 cells by inhibiting fatty acid β-oxidation.

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Enhanced cell survival in prepubertal testicular tissue cryopreserved with membrane lipids and antioxidants rich cryopreservation medium
Reyon Dcunha, Anjana Aravind, Smitha Bhaskar, Sadhana Mutalik, Srinivas Mutalik, Sneha Guruprasad Kalthur, Anujith Kumar, Padmaraj Hegde, Satish Kumar Adiga, Yulian Zhao, Nagarajan Kannan, Thottethodi Subrahmanya Keshava Prasad, Guruprasad Kalthur
Cell and Tissue Research.2025; 399(1): 97. CrossRef
Lipid metabolism in ferroptosis: mechanistic insights and therapeutic potential
Daoyun Sun, Longfei Wang, Yufan Wu, Yi Yu, Yufeng Yao, Hongju Yang, Chunlin Hao
Frontiers in Immunology.2025;[Epub] CrossRef
FABP4 inhibition protects renal tubular cells and ameliorates renal inflammation in diabetic kidney disease
Yen‐Wen Wu, Jaw‐Wen Chen, Liang-Yu Lin, Jih-Hsin Huang, Chia‐Chi Chang, Ting‐Ting Chang
Biochemical Pharmacology.2025; 236: 116899. CrossRef
Augmenter of liver regeneration knockout aggravates tubular ferroptosis and macrophage activation by regulating carnitine palmitoyltransferase‐1A‐induced lipid metabolism in diabetic nephropathy
Yuanyuan Zhang, Zheng Zhang, Lili Huang, Chunxia Wang, Pengfei Yang, Ling Zhang, Xiaohui Liao
Acta Physiologica.2024;[Epub] CrossRef
Fatty Acid Binding Protein-4 Silencing Inhibits Ferroptosis to Alleviate Lipopolysaccharide-induced Injury of Renal Tubular Epithelial Cells by Blocking Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Signaling
Suo Xu, Jiye Luo, Yanli Wang, Xiaobing Chen
Journal of Physiological Investigation.2024; 67(1): 47. CrossRef
Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications
Zhili Wu, Yanru Zhu, Wenchao Liu, Balamuralikrishnan Balasubramanian, Xiao Xu, Junhu Yao, Xinjian Lei
Antioxidants.2024; 13(3): 352. CrossRef
Investigating the Role of FABP4 in Diabetes and Obesity and the Influence of Age and Ethnicity: A Comprehensive Analysis of a Cohort from the KEDP-Study
Mohammed A. Abdalla, Jehad Abubaker, Mohamed Abu-Farha, Irina Al-Khairi, Preethi Cherian, Mohammad G. Qaddoumi, Fatema Al-Rashed, Thangavel Alphonse Thanaraj, Ahmed N. Albatineh, Fahd Al-Mulla
International Journal of Molecular Sciences.2024; 25(9): 4578. CrossRef
Mitochondrial metabolic reprogramming in diabetic kidney disease
Xiaoting Fan, Meilin Yang, Yating Lang, Shangwei Lu, Zhijuan Kong, Ying Gao, Ning Shen, Dongdong Zhang, Zhimei Lv
Cell Death & Disease.2024;[Epub] CrossRef
Inhibition of FABP4 Ameliorates IL-13-Induced Inflammatory Response and Barrier Dysfunction in Nasal Mucosal Epithelial Cells through the Regulation of Ferroptosis
Shanshan Qi
Cell Biochemistry and Biophysics.2024; 83(1): 977. CrossRef
Unraveling Ferroptosis: A New Frontier in Combating Renal Fibrosis and CKD Progression
Rui Jin, Yue Dai, Zheng Wang, Qinyang Hu, Cuntai Zhang, Hongyu Gao, Qi Yan
Biology.2024; 14(1): 12. CrossRef
Mechanisms and regulations of ferroptosis
Xu-Dong Zhang, Zhong-Yuan Liu, Mao-Sen Wang, Yu-Xiang Guo, Xiang-Kun Wang, Kai Luo, Shuai Huang, Ren-Feng Li
Frontiers in Immunology.2023;[Epub] CrossRef
Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases
Yumin Wang, Jing Hu, Shuang Wu, Joshua S. Fleishman, Yulin Li, Yinshi Xu, Wailong Zou, Jinhua Wang, Yukuan Feng, Jichao Chen, Hongquan Wang
Signal Transduction and Targeted Therapy.2023;[Epub] CrossRef

Diabetes, Obesity and Metabolism
Sleep Duration and the Risk of Type 2 Diabetes: A Community-Based Cohort Study with a 16-Year Follow-up: Da Young Lee, Inha Jung, So Young Park, Ji Hee Yu, Ji A Seo, Kyeong Jin Kim, Nam Hoon Kim, Hye Jin Yoo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Seung Ku Lee, Chol Shin, Nan Hee Kim; Endocrinol Metab. 2023;38(1):146-155. Published online February 6, 2023; DOI: https://doi.org/10.3803/EnM.2022.1582

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Background
We aimed to investigate the moderating effects of obesity, age, and sex on the association between sleep duration and the development of diabetes in Asians.
Methods
We analyzed data from a cohort of the Korean Genome and Epidemiology Study conducted from 2001 to 2020. After excluding shift workers and those with diabetes at baseline, 7,407 participants were stratified into three groups according to sleep duration: ≤5 hours/night, >5 to 7 hours/night (reference), and >7 hours/night. The Cox proportional hazards analyses were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes mellitus (T2DM). Subgroup analyses were performed according to obesity, age, and sex.
Results
During 16 years of follow-up, 2,024 cases of T2DM were identified. Individuals who slept ≤5 h/night had a higher risk of incident diabetes than the reference group (HR, 1.17; 95% CI, 1.02 to 1.33). The subgroup analysis observed a valid interaction with sleep duration only for obesity. A higher risk of T2DM was observed in the ≤5 hours/night group in non-obese individuals, men, and those aged <60 years, and in the >7 hours/night group in obese individuals (HRs were 1.34 [95% CI, 1.11 to 1.61], 1.22 [95% CI, 1 to 1.49], and 1.18 [95% CI, 1.01 to 1.39], respectively).
Conclusion
This study confirmed the effect of sleep deprivation on the risk of T2DM throughout the 16-year follow-up period. This impact was confined to non-obese or young individuals and men. We observed a significant interaction between sleep duration and obesity.

Citations

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Sleep features and the risk of type 2 diabetes mellitus: a systematic review and meta-analysis
Hongyi Liu, Hui Zhu, Qinkang Lu, Wen Ye, Tao Huang, Yuqiong Li, Bingqi Li, Yingxin Wu, Penghao Wang, Tao Chen, Jin Xu, Lindan Ji
Annals of Medicine.2025;[Epub] CrossRef
The potential impact of habitual sleep quality on glycaemic control and inflammation: A study on geriatric patients recently diagnosed with type 2 diabetes mellitus (T2DM)
Nadia Hussain, Amal Hussain Ibrahim Al Haddad, Saima Abbass, Zina Alfahl
Sleep Medicine: X.2025; 9: 100139. CrossRef
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Yu Cheng, Yuchuan Ding, Ahmed Elmadhoun, Xunming Ji, Xiaokun Geng
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Attention to Innate Circadian Rhythm and the Impact of Its Disruption on Diabetes
Da Young Lee, Inha Jung, So Young Park, Ji Hee Yu, Ji A Seo, Kyeong Jin Kim, Nam Hoon Kim, Hye Jin Yoo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Nan Hee Kim
Diabetes & Metabolism Journal.2024; 48(1): 37. CrossRef
Role of Sleep and Sleep Disorders in Cardiometabolic Risk: a Review and Update
Shaden O. Qasrawi, Ahmed S. BaHammam
Current Sleep Medicine Reports.2024; 10(1): 34. CrossRef
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Vera Birrer, Mohamed Elgendi, Olivier Lambercy, Carlo Menon
npj Digital Medicine.2024;[Epub] CrossRef
Replication Study of Genome Wide Association Study of Sleep Duration in Korean Association Resources Cohort
Seok-Ho Cho, Seon-Ah Kim, Hyun-Seok Jin, Hong Sung Kim
Biomedical Science Letters.2024; 30(2): 86. CrossRef
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Chun-Kwan O, Juliana C. N. Chan
Nature Metabolism.2024; 6(8): 1435. CrossRef
Mechanisms, consequences and role of interventions for sleep deprivation: Focus on mild cognitive impairment and Alzheimer’s disease in elderly
Upasana Mukherjee, Ujala Sehar, Malcolm Brownell, P. Hemachandra Reddy
Ageing Research Reviews.2024; 100: 102457. CrossRef
The Relationship Between the Risk of Type 2 Diabetes and Insomnia Severity and Sleep Duration in Academicians
Tuğba Bilgehan, Esra Çalık Var
Sağlık Bilimleri Üniversitesi Hemşirelik Dergisi.2024; 6(3): 203. CrossRef
All That Glitters Is Not Gold: The Same Sleep Time, but Different Diabetogenic Outcomes
Bohye Kim, Obin Kwon
Endocrinology and Metabolism.2023; 38(1): 78. CrossRef
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Ali Darraj
Cureus.2023;[Epub] CrossRef

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Risk for Newly Diagnosed Type 2 Diabetes Mellitus after COVID-19 among Korean Adults: A Nationwide Matched Cohort Study: Jong Han Choi, Kyoung Min Kim, Keeho Song, Gi Hyeon Seo; Endocrinol Metab. 2023;38(2):245-252. Published online April 5, 2023; DOI: https://doi.org/10.3803/EnM.2023.1662

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Background
Coronavirus disease 2019 (COVID-19) can cause various extrapulmonary sequelae, including diabetes. However, it is unclear whether these effects persist 30 days after diagnosis. Hence, we investigated the incidence of newly diagnosed type 2 diabetes mellitus (T2DM) in the post-acute phase of COVID-19.
Methods
This cohort study used data from the Health Insurance Review and Assessment Service, a representative national healthcare database in Korea. We established a cohort of 348,180 individuals diagnosed with COVID-19 without a history of diabetes between January 2020 and September 2021. The control group consisted of sex- and age-matched individuals with neither a history of diabetes nor COVID-19. We assessed the hazard ratios (HR) of newly diagnosed T2DM patients with COVID-19 compared to controls, adjusted for age, sex, and the presence of hypertension and dyslipidemia.
Results
In the post-acute phase, patients with COVID-19 had an increased risk of newly diagnosed T2DM compared to those without COVID-19 (adjusted HR, 1.30; 95% confidence interval [CI], 1.27 to 1.33). The adjusted HRs of non-hospitalized, hospitalized, and intensive care unit-admitted patients were 1.14 (95% CI, 1.08 to 1.19), 1.34 (95% CI, 1.30 to 1.38), and 1.78 (95% CI, 1.59 to 1.99), respectively. The risk of T2DM in patients who were not administered glucocorticoids also increased (adjusted HR, 1.29; 95% CI, 1.25 to 1.32).
Conclusion
COVID-19 may increase the risk of developing T2DM beyond the acute period. The higher the severity of COVID-19 in the acute phase, the higher the risk of newly diagnosed T2DM. Therefore, T2DM should be included as a component of managing long-term COVID-19.

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Diabetes, Obesity and Metabolism.2025; 27(2): 767. CrossRef
Comparison of incidence trends of early-onset and late-onset type 2 diabetes in the Asia-Pacific region, 1990-2021: a join point regression analysis based on the global burden of disease study 2021
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Frontiers in Endocrinology.2025;[Epub] CrossRef
New-Onset Diabetes Mellitus in COVID-19: A Scoping Review
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Walter Vena, Stella Pigni, Nazarena Betella, Annalisa Navarra, Marco Mirani, Gherardo Mazziotti, Andrea G. Lania, Antonio C. Bossi
Human Vaccines & Immunotherapeutics.2024;[Epub] CrossRef
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Review Article

Diabetes, obesity and metabolism
Intrarenal Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors on Tubuloglomerular Feedback and Natriuresis: Eun Sil Koh, Gheun-Ho Kim, Sungjin Chung; Endocrinol Metab. 2023;38(4):359-372. Published online July 24, 2023; DOI: https://doi.org/10.3803/EnM.2023.1764

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When sodium-glucose cotransporter-2 (SGLT2) inhibitors were first introduced a decade ago, no one expected them to have substantial effects beyond their known glucose-lowering effects, until the emergence of evidence of their robust renal and cardiovascular benefits showing that they could attenuate progression of kidney disease, irrespective of diabetes, as well as prevent the development of acute kidney injury. Still, the precise and elaborate mechanisms underlying the major organ protection of SGLT2 inhibitors remain unclear. SGLT2 inhibitors inhibit the reabsorption of sodium and glucose in the proximal tubule of the kidney and then recovers tubuloglomerular feedback, whereby SGLT2 inhibitors reduce glomerular hyperfiltration. This simple demonstration of their beneficial effects has perplexed experts in seeking more plausible and as yet undisclosed explanations for the whole effects of SGLT2 inhibitors, including metabolism reprogramming and the modulation of hypoxia, inflammation, and oxidative stress. Given that the renal benefits of SGLT2 inhibitors in patients with kidney disease but without diabetes were comparable to those seen in patients with diabetes, it may be reasonable to keep the emphasis on their hemodynamic actions. In this context, the aim of the present review is to provide a comprehensive overview of renal hemodynamics in individuals with diabetes who are treated with SGLT2 inhibitors, with a focus on natriuresis associated with the regulation of tubuloglomerular feedback and potential aquaresis. Throughout the discussion of alterations in renal sodium and water transports, particular attention will be given to the potential enhancement of adenosine and its receptors following SGLT2 inhibition.

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Veraprapas Kittipibul, Zachary L. Cox, Supavit Chesdachai, Mona Fiuzat, JoAnn Lindenfeld, Robert J. Mentz
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Original Article

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Risk of Cause-Specific Mortality across Glucose Spectrum in Elderly People: A Nationwide Population-Based Cohort Study: Joonyub Lee, Hun-Sung Kim, Kee-Ho Song, Soon Jib Yoo, Kyungdo Han, Seung-Hwan Lee, Committee of Big Data, Korean Endocrine Society; Endocrinol Metab. 2023;38(5):525-537. Published online September 7, 2023; DOI: https://doi.org/10.3803/EnM.2023.1765

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Background
This study investigated the risk of cause-specific mortality according to glucose tolerance status in elderly South Koreans.
Methods
A total of 1,292,264 individuals aged ≥65 years who received health examinations in 2009 were identified from the National Health Information Database. Participants were classified as normal glucose tolerance, impaired fasting glucose, newly-diagnosed diabetes, early diabetes (oral hypoglycemic agents ≤2), or advanced diabetes (oral hypoglycemic agents ≥3 or insulin). The risk of system-specific and disease-specific deaths was estimated using multivariate Cox proportional hazards analysis.
Results
During a median follow-up of 8.41 years, 257,356 deaths were recorded. Diabetes was associated with significantly higher risk of all-cause mortality (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.57 to 1.60); death due to circulatory (HR, 1.49; 95% CI, 1.46 to 1.52), respiratory (HR, 1.51; 95% CI, 1.47 to 1.55), and genitourinary systems (HR, 2.22; 95% CI, 2.10 to 2.35); and neoplasms (HR, 1.30; 95% CI, 1.28 to 1.32). Diabetes was also associated with a significantly higher risk of death due to ischemic heart disease (HR, 1.70; 95% CI, 1.63 to 1.76), cerebrovascular disease (HR, 1.46; 95% CI, 1.41 to 1.50), pneumonia (HR, 1.69; 95% CI, 1.63 to 1.76), and acute or chronic kidney disease (HR, 2.23; 95% CI, 2.09 to 2.38). There was a stepwise increase in the risk of death across the glucose spectrum (P for trend <0.0001). Stroke, heart failure, or chronic kidney disease increased the risk of all-cause mortality at every stage of glucose intolerance.
Conclusion
A dose-dependent association between the risk of mortality from various causes and severity of glucose tolerance was noted in the elderly population.

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Review Article

Diabetes, Obesity and Metabolism
Overcoming Therapeutic Inertia as the Achilles’ Heel for Improving Suboptimal Diabetes Care: An Integrative Review: Boon-How Chew, Barakatun-Nisak Mohd-Yusof, Pauline Siew Mei Lai, Kamlesh Khunti; Endocrinol Metab. 2023;38(1):34-42. Published online February 16, 2023; DOI: https://doi.org/10.3803/EnM.2022.1649

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The ultimate purpose of diabetes care is achieving the outcomes that patients regard as important throughout the life course. Despite advances in pharmaceuticals, nutraceuticals, psychoeducational programs, information technologies, and digital health, the levels of treatment target achievement in people with diabetes mellitus (DM) have remained suboptimal. This clinical care of people with DM is highly challenging, complex, costly, and confounded for patients, physicians, and healthcare systems. One key underlying problem is clinical inertia in general and therapeutic inertia (TI) in particular. TI refers to healthcare providers’ failure to modify therapy appropriately when treatment goals are not met. TI therefore relates to the prescribing decisions made by healthcare professionals, such as doctors, nurses, and pharmacists. The known causes of TI include factors at the level of the physician (50%), patient (30%), and health system (20%). Although TI is often multifactorial, the literature suggests that 28% of strategies are targeted at multiple levels of causes, 38% at the patient level, 26% at the healthcare professional level, and only 8% at the healthcare system level. The most effective interventions against TI are shorter intervals until revisit appointments and empowering nurses, diabetes educators, and pharmacists to review treatments and modify prescriptions.

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Review Articles

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The Benefits Of Continuous Glucose Monitoring In Pregnancy: Jee Hee Yoo, Jae Hyeon Kim; Endocrinol Metab. 2023;38(5):472-481. Published online October 11, 2023; DOI: https://doi.org/10.3803/EnM.2023.1805

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Previous studies have consistently demonstrated the positive effects of continuous glucose monitoring (CGM) on glycemic outcomes and complications of diabetes in people with type 1 diabetes. Guidelines now consider CGM to be an essential and cost-effective device for managing type 1 diabetes. As a result, insurance coverage for it is available. Evidence supporting CGM continues to grow and expand to broader populations, such as pregnant people with type 1 diabetes, people with type 2 diabetes treated only with basal insulin therapy, and even type 2 diabetes that does not require insulin treatment. However, despite the significant risk of hyperglycemia in pregnancy, which leads to complications in more than half of affected newborns, CGM indications and insurance coverage for those patients are unresolved. In this review article, we discuss the latest evidence for using CGM to offer glycemic control and reduce perinatal complications, along with its cost-effectiveness in pregestational type 1 and type 2 diabetes and gestational diabetes mellitus. In addition, we discuss future prospects for CGM coverage and indications based on this evidence.

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Diabetes, Obesity and Metabolism
Glucagon-Like Peptide 1 Therapy: From Discovery to Type 2 Diabetes and Beyond: Adie Viljoen, Stephen C. Bain; Endocrinol Metab. 2023;38(1):25-33. Published online February 6, 2023; DOI: https://doi.org/10.3803/EnM.2022.1642

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The therapeutic benefits of the incretin hormone, glucagon-like peptide 1 (GLP1), for people with type 2 diabetes and/or obesity, are now firmly established. The evidence-base arising from head-to-head comparative effectiveness studies in people with type 2 diabetes, as well as the recommendations by professional guidelines suggest that GLP1 receptor agonists should replace more traditional treatment options such as sulfonylureas and dipeptidyl-peptidase 4 (DPP4) inhibitors. Furthermore, their benefits in reducing cardiovascular events in people with type 2 diabetes beyond improvements in glycaemic control has led to numerous clinical trials seeking to translate this benefit beyond type 2 diabetes. Following early trial results their therapeutic benefit is currently being tested in other conditions including fatty liver disease, kidney disease, and Alzheimer’s disease.

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Brief Report

Diabetes, obesity and metabolism
Performance of Simple Fibrosis Score in Non-Alcoholic Fatty Liver Disease with and without Type 2 Diabetes: Seung Min Chung, Min Kyu Kang, Jun Sung Moon, Jung Gil Park; Endocrinol Metab. 2023;38(2):277-281. Published online March 13, 2023; DOI: https://doi.org/10.3803/EnM.2022.1635

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This cross-sectional study enrolled 267 patients with metabolic risk factors and established non-alcoholic fatty liver disease in the prospective cohort. The performance of fibrosis-4 (FIB-4) score (≥1.3) to diagnose advanced fibrosis using transient elastography (liver stiffness measurement [LSM] ≥8 kPa) was analyzed. Comparing patients with type 2 diabetes (T2D, n=87) and without (n=180), not FIB-4, but LSM was significantly higher in T2D (P=0.026). The prevalence of advanced fibrosis was 17.2% in T2D and 12.8% in non-T2D. FIB-4 exhibited higher proportion of false negatives in T2D patients (10.9%) than those without (5.2%). The diagnostic performance of FIB-4 was suboptimal in T2D (area under curve [AUC], 0.653; 95% confidence interval [CI], 0.462 to 0.844) compared to that in non-T2D (AUC, 0.826; 95% CI, 0.724 to 0.927). In conclusion, patients with T2D might be beneficial to conduct transient elastography without screening to avoid missing advanced fibrosis.

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