Endocrinology and Metabolism

Original Articles

Efficacy and Safety of Stage 5 Connected Insulin Pens in Type 1 or Type 2 Diabetes: Randomized Controlled Trial Protocol: Ji Yoon Kim, Nam Hoon Kim, Soo Heon Kwak, Chang Hee Jung, Eun Seok Kang, Jun Sung Moon, Sun Joon Moon, So Yoon Kwon, Jee Hee Yoo, Younghoon Kim, Tae-min Lee, Chung-il Yang, Jae Hyeon Kim, Sang-Man Jin; Received July 26, 2025 Accepted October 13, 2025 Published online December 12, 2025; DOI: https://doi.org/10.3803/EnM.2025.2579 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
Stage 2 or 3 connected insulin pens (CIPs) refer to tracking insulin pens that are capable of transmitting insulin dose data via cloud connectivity. Stage 4 CIPs feature a bolus calculator that determines appropriate insulin doses based on real-time continuous glucose monitoring (CGM) data, carbohydrate intake, previous dosing history, and preset parameters. Stage 5 CIPs additionally offer advanced decision-support features, such as education modules and coaching. However, the efficacy and safety of Stage 5 CIPs have not yet been established.
Methods
In this prospective, open-label, parallel-group, multicenter, randomized controlled trial, we will include adults aged ≥19 and <75 years with type 1 or type 2 diabetes receiving multiple daily insulin injections (MDI) and having glycosylated hemoglobin (HbA1c) levels of 7.5% to 12.0%. In total, 152 participants will be randomized in a 1:1 ratio to receive either Stage 5 CIPs with CGM or tracking insulin pens with CGM. Stage 5 CIPs include a Setup Wizard that recommends individualized initial settings and an algorithm that provides advanced insulin dosing guidance based on analyses of each participant’s CGM and insulin injection data. The primary outcome will be the change in HbA1c levels from baseline to week 12 (ClinicalTrials.gov, NCT07004153).
Conclusion
This trial will determine whether Stage 5 CIPs are superior to tracking insulin pens in improving glycemic control among adults with type 1 or type 2 diabetes treated with MDI. Overall, this study may offer a promising strategy for enhancing the management and outcomes of patients with diabetes.

Impact of Carbohydrate Intake Fluctuations on Glucose Profiles: Insights from Continuous Glucose Monitoring-Based Patient Clustering: Hyun Ah Kim, Kyung Hee Kim, Young Lee, Yoon-Ju Song, Joon Ho Moon, Sung Hee Choi, Tae Jung Oh; Received June 4, 2025 Accepted September 15, 2025 Published online December 12, 2025; DOI: https://doi.org/10.3803/EnM.2025.2486 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
Continuous glucose monitoring (CGM) is widely applied in daily glucose management. However, its potential to categorize individuals based on glucose profiles is not fully established. This study employed CGM-based patient clustering and examined nutritional factors influencing glucose patterns.
Methods
This prospective observational study enrolled 34 individuals with diabetes. Retrospective professional CGM was conducted over 7 days, during which food intake was recorded. K-means clustering was performed using CGM-derived coefficient of variation (CV) and time in range. Macronutrient intake and its fluctuations were compared across clusters.
Results
Participants were grouped into cluster 1 (well-controlled), cluster 2 (highest CV), and cluster 3 (highest mean glucose). Baseline clinical characteristics, daily energy intake (kcal), and macronutrient intake did not differ significantly among clusters. However, carbohydrate intake fluctuations were greater in cluster 3 (CV 41.0%±32.1%, standard deviation [SD] 502.1±363.4 kcal) than in cluster 1 (CV 21.9%±9.0%, SD 260.2±94.1 kcal) and cluster 2 (CV 19.2%±9.1%, SD 250.2±126.1 kcal) (P=0.123 for CV; P=0.024 for SD). The SD (kcal) of carbohydrate intake was positively correlated with mean glucose levels (rho=0.88, P=0.023).
Conclusion
CGM enables categorization of individuals based on glucose profiles, and higher carbohydrate intake fluctuations are associated with poorer glycemic control. Personalized dietary strategies, particularly stabilizing carbohydrate intake, may support better glucose management in individuals with high mean glucose and low CV.

Distinct Pituitary-Adrenal Responses to Hypoglycemia in Type 1 and Type 2 Diabetes: Yun Hu, Reng-na Yan, Ting-ting Cai, Xiao-wei Zhu, Jian-hua Ma, Bo Ding; Received May 31, 2025 Accepted August 20, 2025 Published online December 3, 2025; DOI: https://doi.org/10.3803/EnM.2025.2479 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Hypoglycemia remains a major barrier to optimal glycemic control in diabetes. Counter-regulatory hormonal responses, particularly those involving the pituitary and adrenal systems, play a central role in mitigating hypoglycemia, yet differences between diabetes subtypes are not well characterized. We aimed to investigate pituitary-target gland responses to hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM).
Methods
We enrolled drug-naive patients with newly diagnosed T2DM or T1DM, along with controls who did not have diabetes. Participants with diabetes received insulin pump therapy until normoglycemia was achieved. Hyperinsulinemic euglycemic-hypoglycemic clamps were then performed in all participants. Hormonal profiles of the pituitary-adrenal axis and C-peptide were serially measured during the clamps.
Results
During hypoglycemic clamps, C-peptide, thyroid-stimulating hormone, estradiol, and testosterone decreased, whereas prolactin, adrenocorticotropic hormone (ACTH), cortisol, and growth hormone (GH) increased significantly according to repeatedmeasures analysis of variance (ANOVA) (P<0.05 for all). Compared to controls and T2DM, patients with T1DM exhibited elevated basal GH (P=0.002) and an exaggerated GH response to hypoglycemia (P=0.002), with earlier onset and sustained elevation. In contrast, patients with T2DM showed higher ACTH (P=0.024) and cortisol (P=0.043) levels during hypoglycemia compared to controls and T1DM. Relative to the T1DM group, the T2DM group demonstrated lower testosterone and higher estradiol levels during hypoglycemia (P<0.001 for both).
Conclusion
Distinct diabetes subtypes demonstrate divergent pituitary-adrenal counter-regulatory responses to hypoglycemia, suggesting unique pathogenic mechanisms contributing to glycemic variability. The exaggerated GH response in T1DM may aggravate glucose fluctuations, whereas elevated ACTH and cortisol in T2DM could perpetuate insulin resistance.

A Nomogram for End-Stage Renal Disease Prediction in Patients with Type 2 Diabetes Mellitus: A Nationwide Cohort Study in Korea: Inha Jung, Bong-Seong Kim, So Young Park, Da Young Lee, Ji Hee Yu, Ji A Seo, Kyung-Do Han, Nan Hee Kim; Received July 22, 2025 Accepted September 18, 2025 Published online November 12, 2025; DOI: https://doi.org/10.3803/EnM.2025.2570 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Despite the rising incidence of end-stage renal disease (ESRD) among individuals with type 2 diabetes mellitus (T2DM) in Korea, no predictive model or nomogram has been developed using a nationwide cohort. In this study, we developed a nomogram to predict the long-term risk of ESRD in patients with T2DM using a large-scale, population-based Korean database.
Methods
Using the Korean National Health Insurance Database, patients with T2DM who underwent health examinations between 2015 and 2016 were assigned as development (n=1,744,277) and validation (n=747,407) cohorts. New ESRD cases were identified using codes for renal replacement therapy. A Cox proportional hazards regression model was used to derive a risk-scoring system, and 13 variables were selected. A risk score nomogram was then created to estimate the risk of ESRD.
Results
In the development cohort, 8,631 patients with T2DM developed ESRD during a follow-up period of 4.8±0.9 years. After multivariable adjustment, significant predictors of ESRD included male sex, current smoking, physical inactivity, low income, low body mass index, hypertension, low-density lipoprotein cholesterol ≥160 mg/dL, chronic kidney disease, insulin use, and longer duration of T2DM. A final nomogram incorporating 13 variables was developed to estimate the individual probability of ESRD. The concordance index for ESRD prediction in the validation cohort was 0.906 (95% confidence interval, 0.9 to 0.912).
Conclusion
This 13-variable nomogram provides a simple tool for identifying patients with T2DM at high risk of ESRD and may aid in early intervention.

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Impact of Glucose Metabolism Status on the Association between Apolipoprotein A-I and Ischemic Risk in Patients with Coronary Artery Disease: A Large-Sample Cohort Study: Kailun Yan, Jiawen Li, Kexin Zhang, Menglu Liu, Pei Zhu, Xiaofang Tang, Deshan Yuan, Yuejin Yang, Runlin Gao, Jinqing Yuan, Xueyan Zhao; Endocrinol Metab. 2025;40(6):904-915. Published online November 7, 2025; DOI: https://doi.org/10.3803/EnM.2025.2407

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Abstract PDF Supplementary Material PubReader ePub: Background
Apolipoprotein A-I (ApoA-I) is a key cardioprotective lipoprotein. Nevertheless, it remains unclear how ApoA-I relates to ischemic risk across glucose metabolism statuses in patients with coronary artery disease (CAD). This study investigated whether glucose metabolism status influences the association between ApoA-I and ischemic risk in CAD patients.
Methods
This cohort study included 10,724 consecutive CAD patients undergoing percutaneous coronary intervention, who were classified into diabetes mellitus (DM), pre-DM, and normal glucose regulation (NGR) groups. The primary clinical endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction, revascularization, and stroke.
Results
Of the 10,232 patients ultimately included, 2,139 (20.9%) experienced MACCE over 5 years. A significant interaction was observed between ApoA-I levels and glucose metabolism status (P for interaction=0.041). In the DM group, an L-shaped association between ApoA-I and MACCE was found, with lower ApoA-I levels linked to a higher risk of MACCE (P for non-linearity= 0.044). Multivariate Cox regression analysis showed that patients in the lowest quintile of ApoA-I had a 1.327-fold increased risk of MACCE compared to those at the lowest risk (hazard ratio, 1.327; 95% confidence interval, 1.097 to 1.604). However, no significant association was observed in the pre-DM or NGR groups (both P>0.05).
Conclusion
This large-scale, 5-year follow-up study is the first to demonstrate that lower ApoA-I levels are associated with increased MACCE risk in CAD patients with DM, highlighting the potential value of ApoA-I in risk stratification and as a therapeutic target.

Brief Report

Diabetes, obesity and metabolism
Early Dose Escalation of Tirzepatide after Switching from Semaglutide in Type 2 Diabetes Mellitus: Noboru Kurinami, Masafumi Takada, Seigo Sugiyama, Akira Yoshida, Kunio Hieshima, Tomoko Suzuki, Fumio Miyamoto, Keizo Kajiwara, Katsunori Jinnouchi, Kenji Ashida, Masatoshi Nomura, Hideaki Jinnouchi; Endocrinol Metab. 2025;40(6):1012-1015. Published online October 15, 2025; DOI: https://doi.org/10.3803/EnM.2025.2420

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Abstract PDF PubReader ePub: Tirzepatide has demonstrated greater efficacy than semaglutide in improving glycemic control and reducing body weight in patients with type 2 diabetes mellitus (T2DM). However, the optimal tirzepatide dose following a switch from 1.0 mg of semaglutide remains unclear. This retrospective study included 15 T2DM patients who switched to tirzepatide due to inadequate weight loss. All patients started tirzepatide at 2.5 mg, with escalation to either 7.5 mg (n=10) or 10 mg (n=5). Changes in glycated hemoglobin (HbA1c) and body weight were assessed over a 3-month period. The 10 mg group experienced a significant reduction in HbA1c (−0.7%±0.3%, P<0.01) and a non-significant trend toward weight loss (−6.6±5.4 kg, P=0.07). In contrast, no significant changes were observed in the 7.5 mg group. There were no statistically significant differences between groups. Since 10 mg of tirzepatide significantly improved glycemic control after switching from 1.0 mg of semaglutide, early escalation to 10 mg may be beneficial for patients who respond inadequately to semaglutide.

Original Articles

Effects of Progranulin Deficiency on Inflammation and Fibrosis in the Kidneys and Liver of Diabetic Mice Fed a High-Fat Diet: Hiroko Sakuma, Maki Murakoshi, Shinji Hagiwara, Terumi Shibata, Yusuke Suzuki, Tomohito Gohda; Received February 6, 2025 Accepted July 23, 2025 Published online September 30, 2025; DOI: https://doi.org/10.3803/EnM.2025.2339 [Epub ahead of print]

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Background
Progranulin (PGRN) is an important regulator of inflammation, insulin resistance, and autophagy. However, the effects of PGRN deficiency on these processes in the kidneys and liver in diabetes remain unclear. In addition, the differential effects of PGRN deficiency and sodium-glucose co-transporter-2 (SGLT2) inhibitors on these organs are unknown.
Methods
Three diabetic mouse models were used: high-fat diet and nicotinamide/streptozotocin-induced diabetic wild-type (WT) and PGRN-knockout (KO) mice (WT-diabetes mellitus [DM] and KO-DM, respectively) and WT-DM mice treated with an SGLT2 inhibitor (tofogliflozin; WT-DM/Tofo).
Results
Despite similar glycemic control in WT-DM/Tofo and KO-DM mice, expression of inflammation- and fibrosis-related genes in the kidneys was highest in WT-DM mice, lower in KO-DM mice, and lowest in WT-DM/Tofo mice. WT-DM/Tofo mice also showed increased anti-microtubule-associated protein 1A/1B-light chain 3B and decreased p62 protein levels compared with KO-DM mice. In contrast, hepatic mRNA levels related to inflammation and fibrosis were improved in both WT-DM/Tofo and KO-DM mice. Moreover, hepatic protein levels of peroxisome proliferator-activated receptor γ (PPARγ) were elevated in both groups compared with WT-DM mice, while those of PPARα were increased in WT-DM/Tofo mice compared with both WT-DM and KO-DM mice.
Conclusion
Kidney inflammation and fibrosis were ameliorated in WT-DM/Tofo mice, but these improvements were limited by autophagy insufficiency in KO-DM mice. Additionally, both WT-DM/Tofo and KO-DM mice demonstrated improved liver inflammation and fibrosis; in the former, this was associated with enhanced fatty acid oxidation via PPARα activation, while in the latter, it appeared to result from improved insulin sensitivity and anti-inflammatory effects through PPARγ activation.

Citations

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SGLT2 Inhibitors as Systemic Metabolic Modulators: Linking Glucose Excretion to Liver Function Restoration
Seung Wan Noh, Han Sol Ryu, Yong-Ho Kim, Byung-Chul Oh
Endocrinology and Metabolism.2025; 40(6): 851. CrossRef

Reduced Sphingosine-1-Phosphate Levels Exacerbate Type 2 Diabetes Mellitus and Associated Complications in a High-Fat Diet Mouse Model: Shih-Chang Hsu, Ching-Lu Chen, Chung Te Liu, Hung-Chieh Lo, Ying-Kuo Liu, Pei-Song Gao, Shau-Ku Huang, Chin-Wang Hsu; Received March 4, 2025 Accepted May 28, 2025 Published online August 5, 2025; DOI: https://doi.org/10.3803/EnM.2025.2360 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Type 2 diabetes mellitus (T2DM) is increasingly prevalent and frequently associated with obesity, insulin resistance, nonalcoholic fatty liver disease, and chronic kidney disease. Emerging evidence suggests sphingosine-1-phosphate (S1P), a bioactive sphingolipid, plays a significant role in the pathogenesis of T2DM. This study aimed to investigate how reduced S1P levels impact T2DM development.
Methods
S1P lyase knock-in (S1PL^C317A KI) mice, characterized by reduced S1P levels due to impaired S1P degradation, were compared with wild-type (WT) mice. Both groups were fed a high-fat diet (HFD) to induce T2DM. Parameters including body weight, insulin resistance, blood glucose levels, hepatic fat accumulation, and kidney pathology were evaluated. Next-generation sequencing was employed to identify differentially expressed genes.
Results
S1PL^C317A KI mice exhibited greater body weight, more pronounced insulin resistance, and higher blood glucose levels compared to WT mice on an HFD. Increased hepatic fat deposition and worsened diabetic kidney disease were also observed in KI mice. Sequencing analysis identified 4,656 differentially expressed genes, notably enriched in mitochondrial and bioenergetic pathways, including 133 diabetes-related genes.
Conclusion
Reduced S1P levels exacerbate T2DM symptoms, indicating that therapeutic targeting of S1P pathways may offer promising strategies for treating T2DM and its related complications.

Early-Onset Dementia Risk Escalates with Diabetes Duration: Insights from a Nationwide Cohort Study: Ji-Hong Park, Sun-Joon Moon, Da Yeon Lee, Ji-Hee Ko, Han Na Jang, Hye-Mi Kwon, Se-Eun Park, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee; Received December 17, 2024 Accepted May 19, 2025 Published online July 17, 2025; DOI: https://doi.org/10.3803/EnM.2024.2287 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The prevalence of diabetes mellitus and early-onset dementia (EOD), defined as dementia diagnosed at an age <65 years, is increasing worldwide, with significant socioeconomic implications. We investigated the association between diabetes, prediabetes, and EOD, focusing on the influence of diabetes duration on EOD risk.
Methods
Using the Korean National Health Insurance Service database, we analyzed data from 1,979,509 patients aged 40–60 years who underwent health checkups in 2009. Patients were categorized into five groups: normal, impaired fasting glucose (IFG), newly diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years. Cox proportional hazard models were used to estimate the adjusted hazard ratios (aHRs) for EOD after adjusting for demographic and clinical covariates.
Results
During the observation period (mean 7.75 years), 8,921 patients with EOD were identified. The diabetes group demonstrated a significantly higher incidence of EOD compared to the normal group (aHR, 1.334; 95% confidence interval [CI], 1.226 to 1.451). EOD risk increased with longer diabetes duration, with the highest risk observed in patients with diabetes ≥5 years (aHR, 1.543; 95% CI, 1.368 to 1.741). No significant difference was observed between the IFG and normal groups (aHR, 0.989; 95% CI, 0.938 to 1.043). Additionally, the hypertension group exhibited a significantly higher incidence of EOD compared to the non-hypertension group (aHR, 1.364; 95% CI, 1.291 to 1.442).
Conclusion
Diabetes is independently associated with increased risk of EOD, and this risk increases with longer diabetes duration. This association remained significant regardless of the presence and duration of hypertension.

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Associations of Alcohol Consumption with All-Cause and Cancer Mortalities in Patients with Type 2 Diabetes Mellitus: A Nationwide Population Cohort Study: Da Yeon Lee, Sun-Joon Moon, Kyung-Do Han, Ji-Hee Ko, Han-na Jang, Hye-Mi Kwon, Se-Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2025;40(6):893-903. Published online July 14, 2025; DOI: https://doi.org/10.3803/EnM.2024.2275

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Background
To investigate the impact of alcohol consumption on all-cause and cancer mortalities in patients with type 2 diabetes (T2D).
Methods
This nationwide cohort study included Korean patients with T2D aged >20 years from a national health exams cohort (2009 to 2012). Participants were categorized based on alcohol consumption: non, mild (<30 g/day), and heavy drinkers (≥30 g/day). Primary outcomes were all-cause and cancer mortality rates. Cox proportional hazard regression analyses were used to calculate adjusted hazard ratios (aHRs) with a 95% confidence interval (CI) with adjustments for age, sex, body mass index, smoking, exercise, comorbidities, diabetes duration, and medications.
Results
Among 2,642,359 participants (median follow-up, 7.8 years), 57.2%, 32.7%, and 10.1% were non, mild, and heavy drinkers, respectively. Compared to non-drinkers, mild alcohol consumption was associated with reduced all-cause mortality (aHR, 0.81; 95% CI, 0.80 to 0.82) and cancer mortality (aHR, 0.88; 95% CI, 0.86 to 0.89), while heavy drinking increased both all-cause (aHR, 1.06; 95% CI, 1.04 to 1.07) and cancer mortalities (aHR, 1.09; 95% CI, 1.06 to 1.11). Subgroup analyses revealed variations: in chronic kidney disease and older age groups, heavy drinkers showed lower risk of all-cause mortality compared to non-drinkers. Regarding cancer mortality, younger and middle-aged groups showed protective effects of alcohol even for heavy drinkers, while females showed linear association between alcohol consumption and cancer mortality.
Conclusion
This study indicates a J-shaped relationship between alcohol consumption and all-cause and cancer mortality risk in patients with T2D, with variations across subgroups. These findings suggest the need for personalized recommendations considering individual risk factors.

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High BMI-attributable female-specific cancers: a comprehensive analysis of the global disease burden and trends from 1990 to 2021 and projections to 2040
Guangming Sun, Junmei Tang, Hao Chen, Yue Zhu, Pan Ren, Hanyue Gan, Wenbin Wu
Frontiers in Oncology.2025;[Epub] CrossRef

Adrenal gland
Deep Learning-Based Adrenal Gland Volumetry for the Prediction of Diabetes: Eu Jeong Ku, Soon Ho Yoon, Seung Shin Park, Ji Won Yoon, Jung Hee Kim; Endocrinol Metab. 2025;40(6):991-1001. Published online June 18, 2025; DOI: https://doi.org/10.3803/EnM.2025.2336

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Abstract PDF Supplementary Material PubReader ePub: Background
The long-term association between adrenal gland volume (AGV) and type 2 diabetes (T2D) remains unclear. We aimed to determine the association between deep learning-based AGV and current glycemic status and incident T2D.
Methods
In this observational study, adults who underwent abdominopelvic computed tomography (CT) for health checkups (2011–2012), but had no adrenal nodules, were included. AGV was measured from CT images using a three-dimensional nnU-Net deep learning algorithm. We assessed the association between AGV and T2D using a cross-sectional and longitudinal design.
Results
We used 500 CT scans (median age, 52.3 years; 253 men) for model development and a Multi-Atlas Labeling Beyond the Cranial Vault dataset for external testing. A clinical cohort included a total of 9708 adults (median age, 52.0 years; 5,769 men). The deep learning model demonstrated a dice coefficient of 0.71±0.11 for adrenal segmentation and a mean volume difference of 0.6± 0.9 mL in the external dataset. Participants with T2D at baseline had a larger AGV than those without (7.3 cm³ vs. 6.7 cm³ and 6.3 cm³ vs. 5.5 cm³ for men and women, respectively, all P<0.05). The optimal AGV cutoff values for predicting T2D were 7.2 cm³ in men and 5.5 cm³ in women. Over a median 7.0-year follow-up, T2D developed in 938 participants. Cumulative T2D risk was accentuated with high AGV compared with low AGV (adjusted hazard ratio, 1.27; 95% confidence interval, 1.11 to 1.46).
Conclusion
AGV, measured using deep learning algorithms, is associated with current glycemic status and can significantly predict the development of T2D.

Diabetes, obesity and metabolism
Fatty Liver Index Dynamics as a Predictor of Hepatocellular Carcinoma in Patients with Type 2 Diabetes Mellitus and Non-Cirrhotic Livers: Eun-Hee Cho, Min Gu Kang, Chang Hun Lee, Shinyoung Oh, Chen Shen, Ha Ram Oh, Young Ran Park, Hyun Lee, Jong Seung Kim, Ji Hyun Park; Endocrinol Metab. 2025;40(6):883-892. Published online May 29, 2025; DOI: https://doi.org/10.3803/EnM.2024.2286

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Type 2 diabetes mellitus (T2DM) is a significant risk factor for hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease; however, surveillance strategies for patients with T2DM, especially without cirrhosis, are inadequate. This study examined whether the fatty liver index (FLI) and its dynamic changes can effectively identify patients with T2DM at increased risk for HCC.
Methods
Data from 92,761 individuals with T2DM aged 40 to 79 who underwent two health screenings (2012 to 2015) were analyzed. The FLI, calculated using waist circumference, body mass index, triglycerides, and gamma-glutamyl transferase, was used to stratify patients by baseline FLI and FLI changes between screenings. HCC cases were identified via International Classification of Diseases codes and reimbursement records (2016 to 2020).
Results
Patients with baseline FLI of 30 to 59.9 had a 1.90-fold higher risk (P<0.01) and those with FLI ≥60 had a 2.94-fold higher risk (P<0.01) of developing HCC compared to those with FLI <30. An increase in FLI from <30 to ≥30 resulted in a 2.10-fold higher risk of HCC (P<0.01), while a reduction in FLI from ≥30 to <30 led to a 0.64-fold lower risk (P=0.03). Protective benefits of FLI reduction took approximately 3 years to manifest.
Conclusion
Baseline and dynamic monitoring of FLI effectively identified HCC risk in T2DM patients with non-cirrhotic livers, supporting early detection and intervention.

Diabetes, obesity and metabolism
Current Status of Delay in Injectable Therapy among Type 2 Diabetes Mellitus Patients in South Korea: Multicenter Retrospective Study (2015–2021): Jong Han Choi, Min Kyong Moon, Hae Jin Kim, Kyung Ae Lee, Hyun Jin Kim, Jung Hae Ko, Jae-Seung Yun, Seung-Hyun Ko, Suk Chon, Nam Hoon Kim; Endocrinol Metab. 2025;40(5):727-736. Published online May 29, 2025; DOI: https://doi.org/10.3803/EnM.2024.2280

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Background
We aimed to assess the therapeutic inertia associated with injectable therapies and the factors influencing glycemic control following these therapies in patients with type 2 diabetes mellitus (T2DM) in South Korea.
Methods
This multicenter, retrospective cohort study included 2,598 T2DM patients aged 20 to 75 years from 10 referral medical centers in South Korea. These patients had been treated with three or four oral antidiabetic drugs (OADs) and were subsequently initiated on insulin (n=1,942) or glucagon-like peptide-1 receptor agonists (GLP-1RAs, n=656) between January 2015 and December 2021. We analyzed the time to initiation of injectable therapy, changes in glycated hemoglobin (HbA1c), and associations between clinical factors and glycemic control.
Results
At the time of injectable therapy initiation, the mean HbA1c was 9.54%, with insulin users having a higher HbA1c level (9.79%) than GLP-1RA users (8.70%). The mean time from starting 3 or 4 OADs to initiating injectable therapy was 3.19 years: 53.5% of patients had started injectable therapy after 2 years, and 24.2% started after 5 years. Among insulin users, older age (P= 0.004), higher body mass index (P=0.035), and lower HbA1c levels at insulin initiation (P<0.001) were associated with better glycemic control. Among GLP-1RA users, only the HbA1c level at therapy initiation (P<0.001) was a significant factor.
Conclusion
This study highlighted significant delays in initiating injectable therapies, particularly insulin, in T2DM patients in South Korea. Early initiation of injectable therapy may improve long-term glycemic control in these patients.

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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

Diabetes, obesity and metabolism
Exploring Sex Differences in Type 2 Diabetes via a Male-Dominant Beta-Cell Cluster from Single-Cell Pancreatic Sequencing of Public Datasets: Nguyen Van Anh, Hyo-Wook Gil, Samel Park, Seongho Ryu; Endocrinol Metab. 2025;40(5):706-717. Published online May 19, 2025; DOI: https://doi.org/10.3803/EnM.2025.2297

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Background
Type 2 diabetes is a complex metabolic disorder characterized by insulin resistance and progressive beta-cell dysfunction. Although sex differences in type 2 diabetes prevalence, progression, and complications have been reported, the molecular mechanisms underlying these differences remain largely unknown. We aimed to utilize single-cell RNA sequencing to identify a beta-cell cluster that is more prevalent in males than in females and exhibits distinct gene expression patterns, gene set enrichment profiles, and cell-cell communication compared to other clusters.
Methods
FASTQ files from four public datasets were preprocessed, aligned to the human genome (GRCh38), and integrated into a high-quality matrix to mitigate batch effects. We focused on beta-cells from type 2 diabetes patients, performed trajectory inference to identify clusters, and conducted differential gene expression and gene set enrichment analyses. These findings were validated using bulk RNA-seq datasets. Additionally, cell-cell communication analysis was performed to identify ligand-receptor interactions, followed by a sensitivity analysis to assess sex-specific differences.
Results
We identified a male-dominant beta-cell cluster (adjusted P value=4.2×10^–6) that displayed unique gene expression patterns and downregulation of pathways associated with protein metabolism and insulin synthesis. Differentially expressed genes (e.g., interleukin 24 [IL24], regulator of G protein signaling like 1 [RGSL1]) were confirmed through bulk analysis. Moreover, the cluster demonstrated distinct communication patterns with other cell types, underscoring sex-specific differences.
Conclusion
We have identified a male-dominant beta-cell cluster characterized by distinct gene expression, signaling pathways, and cell interactions. These findings provide insights into the pathophysiology of type 2 diabetes and may inform the development of more effective, sex-specific therapeutic strategies in the future.

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Exploring Sex-Specific Mechanisms in Type 2 Diabetes Mellitus by Single-Cell Analysis in Pancreatic Islets
Joonyub Lee
Endocrinology and Metabolism.2025; 40(5): 699. CrossRef

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
The Triglyceride-Glucose Index and Risk of End-Stage Renal Disease across Different Durations of Type 2 Diabetes Mellitus: A Longitudinal Cohort Study: Mi-sook Kim, Kyu-Na Lee, Jeongmin Lee, Jeongeun Kwak, Seung-Hwan Lee, Hyuk-Sang Kwon, Jing Hughes, Kyung-Do Han, Eun Young Lee; Endocrinol Metab. 2025;40(5):718-726. Published online May 19, 2025; DOI: https://doi.org/10.3803/EnM.2024.2271

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Background
This study investigated the association between the triglyceride-glucose (TyG) index, a marker of insulin resistance, and the risk of end-stage renal disease (ESRD) in individuals with type 2 diabetes mellitus (T2DM), focusing on variations by diabetes duration.
Methods
We analyzed 1,219,148 Korean adults with T2DM from National Health Insurance Service data who underwent biennial health evaluations (2015 to 2016). ESRD was defined using specific procedural codes (V codes), and Cox proportional hazard models were employed to estimate hazard ratios (HRs) for ESRD across TyG index quartiles and diabetes duration categories, adjusting for various confounders.
Results
Over 6,967,381 person-years of follow-up, 7,548 participants developed ESRD. Higher TyG index quartiles were independently associated with increased risk of ESRD, which was more pronounced with longer diabetes duration. The adjusted HR for ESRD in the highest TyG quartile (Q4) compared to the lowest quartile (Q1) was 1.235 (95% confidence interval [CI], 0.995 to 1.533) in new-onset diabetes, and 1.592 (95% CI, 1.465 to 1.730) in those with diabetes for ≥10 years. Compared to the lowest TyG quartile in new-onset diabetes, the adjusted HR for ESRD in the highest quartile with diabetes duration ≥10 years increased to 10.239 (95% CI, 8.440 to 12.422). Subgroup analysis revealed that a higher TyG index consistently increased the risk of ESRD, with stronger associations observed in younger individuals and those without comorbidities.
Conclusion
The TyG index is a significant predictor of ESRD in T2DM, particularly in those with prolonged diabetes duration. Targeting insulin resistance early may mitigate the risk of ESRD in this population.

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Association between TYG-BMI index and asthma in adults over 45 years of age: analysis of Global Burden of Disease 2021, China Health and Retirement Longitudinal Study, and National Health and Nutrition Examination Survey data
Zhuolin Qin, Longqian Li, Cheng Wang
Journal of Asthma.2025; : 1. CrossRef

Review Article

Diabetes, obesity and metabolism
Prevalence and Current Status of Cardiometabolic Risk Factors in Korean Adults Based on Fact Sheets 2024: Eun-Jung Rhee; Endocrinol Metab. 2025;40(2):174-184. Published online April 24, 2025; DOI: https://doi.org/10.3803/EnM.2025.2398

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Korea has entered ‘super-aged’ society in 2025 with the proportion of people 65 years or older exceeding 20% as of the end of the year 2024. The health burden of cardiovascular diseases increases with age, and the increasing prevalence of cardiovascular risk factors, such as obesity, hypertension, diabetes mellitus, and dyslipidemia, may be linked to increased population-level cardiovascular risk. According to data from 2022, the overall prevalence of obesity reached 38.4%, marking a continued upward trend, based on National Health Insurance medical checkup data. In the combined data of 2021 to 2022, the prevalence of diabetes was 15.5% in Koreans older than 30 years according to the Diabetes Fact Sheet 2024 published by the Korean Diabetes Association, based on data from the Korean National Health and Nutrition Examination Survey. The prevalence of hypertension in the total population of Korea in 2022 was 30% according to the Korean Hypertension Fact Sheet produced by the Korean Society of Hypertension. Lastly, the prevalence of dyslipidemia in 2022 was 40.9% according to the Dyslipidemia Fact Sheet published by the Korean Society of Lipid and Atherosclerosis. In this article, I would like to review the prevalence and current management of cardiovascular risk factors in Korea according to the fact sheets released by various associations in 2024.

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2024 Cardio-cerebrovascular disease fact sheet in Korea
Kyungdo Han, Jin-Hyung Jung, Sang-Suk Choi, Seung-Hyun Ko
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Rishibha Kaushik, B. P. Priyadarshi, Lalit Kumar, Yuvraj Gulati, Madhuri Priyadarshi, S. K. Sinha
International Journal of Advances in Medicine.2025; 12(5): 462. CrossRef
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Original Article

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
The Severity of Diabetes and the Risk of Diabetic Foot Amputation: A National Cohort Study: Jin Yu, Ji-Hyun Kim, Bongseong Kim, Kyungdo Han, Seung Hwan Lee, Mee Kyoung Kim; Endocrinol Metab. 2025;40(4):574-582. Published online April 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2266

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Background
This study aimed to assess whether markers of diabetes severity could serve as predictors for foot amputation risk among patients with type 2 diabetes mellitus.
Methods
We analyzed data from the nationally representative Korean National Health Insurance System database, tracking 2,544,077 patients with type 2 diabetes mellitus who participated in routine health check-ups between 2009 and 2012, with followup extending through the end of 2018. The parameters used to define the diabetes severity score encompassed diabetes duration, insulin usage, the number of oral glucose-lowering medications, the presence of chronic kidney disease, diabetic retinopathy, and cardiovascular disease. Each factor was assigned one point, yielding a cumulative severity score ranging from 0 to 6.
Results
The risk of diabetic foot amputation was predominantly predicted by insulin therapy, diabetic retinopathy, and a prolonged duration of diabetes. The hazard ratios for foot amputation increased with the severity score as follows: 2.31 (95% confidence interval [CI], 2.15 to 2.47) for a score of 1, 4.73 (95% CI, 4.42 to 5.07) for a score of 2, 8.86 (95% CI, 8.24 to 9.53) for a score of 3, 16.95 (95% CI, 15.60 to 18.4) for a score of 4, 23.98 (95% CI, 21.25 to 27.05) for a score of 5, and 37.87 (95% CI, 28.93 to 49.57) for a score of 6.
Conclusion
Specific markers of advanced diabetes effectively identified patients at an elevated risk for diabetic foot amputation.

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Jin Yu, Bongseong Kim, Kyungdo Han, Mee Kyoung Kim
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Association of high-density lipoprotein-related inflammatory indicators with diabetic foot ulcer in patients with diabetes: a population-based study
Renhe Deng, Ruyi Tao, Huiyi Luo, Yueqi Gu, Mengyu Yang, Chaoqi Yin
Diabetology & Metabolic Syndrome.2025;[Epub] CrossRef

Review Article

Diabetes, obesity and metabolism
Advances in Continuous Glucose Monitoring: Clinical Applications: So Yoon Kwon, Jun Sung Moon; Endocrinol Metab. 2025;40(2):161-173. Published online April 8, 2025; DOI: https://doi.org/10.3803/EnM.2025.2370

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Continuous glucose monitoring (CGM) has revolutionized diabetes management, significantly enhancing glycemic control across diverse patient populations. Recent evidence supports its effectiveness in both type 1 and type 2 diabetes management, with benefits extending beyond traditional glucose monitoring approaches. CGM has demonstrated substantial improvements in glycemic control across multiple metrics. Studies report consistent glycosylated hemoglobin reductions of 0.25%–3.0% and notable time in range improvements of 15%–34%. CGM effectively reduces hypoglycemic events, with studies reporting significant reductions in time spent in hypoglycemia. CGM also serves as an educational tool for lifestyle modification, providing real-time feedback that helps patients understand how diet and physical activity affect glucose levels. While skin-related complications remain a concern, technological advancements have addressed many initial concerns. High satisfaction rates and long-term use suggest that device-related issues are manageable with proper education and support. Despite high initial costs, CGM’s prevention of complications and hospitalizations ultimately reduces healthcare expenditures. With appropriate training and support, CGM represents a transformative technology for comprehensive diabetes care.

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Diabetes Research and Clinical Practice.2025; 229: 112951. CrossRef
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Continuous Glucose Monitoring for Pancreatogenic Diabetes After Total Pancreatectomy
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Ji Yoon Kim, Nam Hoon Kim, Soo Heon Kwak, Chang Hee Jung, Eun Seok Kang, Jun Sung Moon, Sun Joon Moon, So Yoon Kwon, Jee Hee Yoo, Younghoon Kim, Tae-min Lee, Chung-il Yang, Jae Hyeon Kim, Sang-Man Jin
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Original Articles

Diabetes, obesity and metabolism
Discrepancies in Dapagliflozin Response in Terms of Glycemic Control and Body Weight Reduction: Ji Eun Jun, Kyoung-Ah Kim, Nan-Hee Kim, Kwan-Woo Lee, In-Kyung Jeong, on Behalf of the BEYOND Investigators; Endocrinol Metab. 2025;40(2):278-288. Published online March 19, 2025; DOI: https://doi.org/10.3803/EnM.2024.2142

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Background
Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduces hyperglycemia and obesity by inhibiting renal glucose reabsorption. This post hoc study evaluated clinical factors influencing patient response to dapagliflozin.
Methods
The analysis focused on patients treated with dapagliflozin (10 mg/day for 52 weeks) within the randomized, double-blind, parallel-group BEYOND trial. Adequate glycemic control (GC) was defined as a reduction in glycated hemoglobin (HbA1c) of ≥ 1.0% or the achievement of an HbA1c level <7.0% at week 52. Significant weight loss (WL) referred to a reduction in body weight of ≥3.0% at week 52. Participants were classified into four groups based on their GC and WL responses: GC+/WL+, GC+/WL−, GC−/WL+, and GC−/WL−.
Results
Among dapagliflozin recipients (n=56), at 52 weeks, HbA1c had decreased by 1.0%±0.8% from baseline, while body weight had declined by 2.4±3.1 kg. Overall, 69.6% of participants achieved GC+, and 57.1% achieved WL+. Male sex and shorter diabetes duration were significantly associated with achieving GC+. Conversely, higher estimated glomerular filtration rate was significantly linked to WL+. The only factor significantly associated with both GC+ and WL+ was shorter diabetes duration (odds ratio, 0.81; 95% confidence interval, 0.68 to 0.97; P=0.023). The GC+ and WL+ groups exhibited favorable responses beginning soon after dapagliflozin therapy was initiated. Furthermore, HbA1c decline was more strongly associated with reduction in visceral fat than with WL.
Conclusion
A short duration of diabetes and early response to treatment appear to represent key factors in maximizing the benefits of dapagliflozin for blood glucose and weight management.

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Identification of IL18/IL18R1 signaling as a predictive biomarker of SGLT2 inhibitor efficacy in type 2 diabetes
I-Jou Teng, Chien-Hsing Lee, Ying-Chen Chen, Sheng-Chiang Su, Chieh-Hua Lu, Peng-Fei Li, Chia-Luen Huang, Li-Ju Ho, Ming-Hsun Lin, Hsin-Ya Liu, Feng-Chih Kuo
iScience.2025; 28(10): 113594. CrossRef
Sodium‐glucose cotransporter 2 inhibitor ameliorates thiazolidinedione‐induced fluid retention through vascular leakage reduction in white adipose tissue
Ji Yoon Kim, Hye‐Min Jang, Hye‐Jin Lee, Ah Hyeon Lee, Dong‐Hoon Kim, Sin Gon Kim, Nam Hoon Kim
Diabetes, Obesity and Metabolism.2025;[Epub] CrossRef

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Association between the Triglyceride-Glucose Index and Cardiovascular Risk and Mortality across Different Diabetes Durations: A Nationwide Cohort Study: Jeongeun Kwak, Kyung-Do Han, Eun Young Lee, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Jeongmin Lee; Endocrinol Metab. 2025;40(4):548-560. Published online March 5, 2025; DOI: https://doi.org/10.3803/EnM.2024.2205

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Background
We aimed to assess the association between triglyceride-glucose (TyG) index and cardiovascular disease (CVD) risk and mortality in a large cohort of diabetes patients.
Methods
A retrospective cohort study of 1,090,485 participants from the Korean National Health Insurance Service database was conducted. Participants were stratified into TyG quartiles.
Results
Higher TyG index quartiles were significantly associated with an increased CVD risk and mortality risk. In fully adjusted models, participants in the highest TyG quartile (Q4) had an 18% higher risk of CVD (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.13 to 1.23) and a 16% higher risk of mortality (HR, 1.16; 95% CI, 1.11 to 1.23) compared to those in the lowest quartile (Q1). The association was particularly pronounced in patients with fasting glucose ≥126 mg/dL (CVD [HR, 1.33; 95% CI, 1.29 to 1.37], mortality [HR, 1.23; 95% CI, 1.20 to 1.26]; P for interaction <0.001). Patients with a diabetes duration of ≥10 years showed the strongest association between the TyG index and CVD risk (HR, 1.44; 95% CI, 1.38 to 1.50), while the mortality risk was particularly elevated in those with a diabetes duration of less than 5 years (HR, 1.23; 95% CI, 1.18 to 1.30). Subgroup analyses revealed stronger associations between TyG index and CVD risk in younger participants, non-obese individuals, and non-smokers.
Conclusion
The TyG index is a significant predictor of CVD and mortality in diabetic patients, particularly in those with poor glycemic control or longer disease duration.

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The Triglyceride-Glucose Index: A Practical Tool for Enhanced Cardiovascular Risk Stratification in Type 2 Diabetes
Jang Won Son
Endocrinology and Metabolism.2025; 40(4): 545. CrossRef
The association between triglyceride-glucose index and all-cause/cardiovascular mortality in patients with different glucose metabolism statuses
Jiajun Liu, Jinhua Kang, Pengpeng Liang, Zhangxiao Song, Guiyun Li, Xueshan Jin, Hongyan Wu
Cardiovascular Diabetology.2025;[Epub] CrossRef
Standardized Triglyceride-Glucose and Plasma Atherogenic Indices as Predictors of Diabetic Nephropathy and Coronary Artery Disease in Patients with Type 1 Diabetes Mellitus
Nazif Yalçın, Nizameddin Koca
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Diabetes, obesity and metabolism
Prevalence of Mortality and Vascular Complications in Older Patients with Diabetes in Korea: Kwang Joon Kim, Jeongmin Lee, Yang Sun Park, Yong-ho Lee, Kyeong Hye Park, Hee-Won Jung, Chang Oh Kim, Man Young Park, Hun-Sung Kim, Bong-Soo Cha; Endocrinol Metab. 2025;40(3):448-458. Published online February 18, 2025; DOI: https://doi.org/10.3803/EnM.2024.2173

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Background
This study investigated the prevalence of diabetes mellitus (DM) and impaired fasting glucose, as well as their management and comorbidities among older Korean adults.
Methods
Data from 269,447 individuals aged 65 years and older from the Korean National Health Insurance Service between 2000 and 2019 were analyzed to evaluate trends in DM prevalence, healthcare utilization, mortality, and complications.
Results
Among 269,447 individuals, 18.6% (n=50,159/269,447) were diagnosed with DM and 27.0% (n=72,670/269,447) had impaired fasting glucose. The DM group had the highest body mass index, waist circumference, and prevalence of current smokers (P<0.001) but not the highest hypertension prevalence. From 2010 to 2019, the prevalence of DM and impaired fasting glucose increased from 15.5% to 21.9% and from 26.0% to 30.6%, respectively. Cancer-related mortality in DM was 1.15 times higher than in those with normal glucose tolerance (P<0.001), and cardiovascular disease-related mortality was 1.32 times higher (P<0.001); all mortalities were higher in female participants. Myocardial infarction (hazard ratio [HR], 1.34; P<0.001), stroke (HR, 1.24; P<0.001), and heart failure (HR, 1.13; P<0.001) were significantly higher in those with DM.
Conclusion
This is the first study to investigate the prevalence of DM and related complications in older individuals based on longterm representative data in Korea. These results highlight the necessity for targeted interventions to enhance management and outcomes in this population.

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Efficacy and safety of switching to ezetimibe 10 mg/rosuvastatin 2.5 mg in Korean patients with type 2 diabetes mellitus and dyslipidaemia: A multicentre, prospective study (EROICA study)
Sangmo Hong, Won J. Kim, Sungrae Kim, Jung H. Park, Eun S. Kang, Min K. Moon, Jae T. Kim, Ji‐Oh Mok, Ki Y. Lee, Cheol‐Young Park, Chang B. Lee
Diabetes, Obesity and Metabolism.2025;[Epub] CrossRef

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Time to Insulin Therapy and Severe Hypoglycemia in Korean Adults Initially Diagnosed with Type 2 Diabetes: A Nationwide Study: You-Bin Lee, Kyungdo Han, Bongsung Kim, So Hee Park, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim, Sang-Man Jin; Endocrinol Metab. 2025;40(3):421-433. Published online February 4, 2025; DOI: https://doi.org/10.3803/EnM.2024.2082

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Abstract PDF Supplementary Material PubReader ePub: Background
We examined the distribution of time to insulin therapy (TIT) post-diabetes diagnosis and the hazard of severe hypoglycemia (SH) according to TIT in Korean adults initially diagnosed with type 2 diabetes (T2D) and who progressed to insulin therapy.
Methods
Using data from the Korean National Health Insurance Service (2002 to 2018), we selected adult incident insulin users (initially diagnosed as T2D) who underwent health examinations between 2009 and 2012. The hazards of SH, recurrent SH, and problematic hypoglycemia were analyzed according to groups categorized using the TIT and clinical risk factors for SH (TIT ≥5 years with risk factors, TIT ≥5 years without risk factors, 3 ≤TIT <5 years, 1 ≤TIT <3 years, and TIT <1 year).
Results
Among 41,637 individuals, 14,840 (35.64%) and 10,587 (25.43%) initiated insulin therapy within <5 and <3 years postdiabetes diagnosis, respectively. During a median 6.53 years, 3,406 SH events occurred. Compared to individuals with TIT ≥5 years and no risk factor for SH, individuals with TIT <3 years had higher outcome hazards in a graded manner (adjusted hazard ratio [95% confidence intervals] for any SH: 1.117 [0.967 to 1.290] in those with 3 ≤TIT <5 years; 1.459 [1.284 to 1.657] in those with 1 ≤ TIT <3 years; and 1.515 [1.309 to 1.754] in those with TIT <1 year). This relationship was more pronounced in the non-obese subpopulation.
Conclusion
Among adults who progressed to insulin therapy after being diagnosed with T2D, a shorter TIT was not uncommon and may predict an increased risk of SH, particularly in non-obese patients.

Review Article

Diabetes, obesity and metabolism
Evolving Characteristics of Type 2 Diabetes Mellitus in East Asia: Joonyub Lee, Kun-Ho Yoon; Endocrinol Metab. 2025;40(1):57-63. Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2193

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In East Asians, type 2 diabetes mellitus (T2DM) is primarily characterized by significant defects in insulin secretion and comparatively low insulin resistance. Recently, the prevalence of T2DM has rapidly increased in East Asian countries, including Korea, occurring concurrently with rising obesity rates. This trend has led to an increase in the average body mass index among East Asian T2DM patients, highlighting the influence of insulin resistance in the development of T2DM within this group. Currently, the incidence of T2DM in Korea is declining, which may indicate potential adaptive changes in insulin secretory capacity. This review focuses on the changing epidemiology of T2DM in East Asia, with a particular emphasis on the characteristics of peak functional β-cell mass.

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Lobeglitazone improves glycaemic control as add‐on therapy to empagliflozin plus metformin in patients with type 2 diabetes mellitus: A double‐blind, randomised, placebo‐controlled trial
Da Hea Seo, Kyung Wan Min, Ho Sang Sohn, Sang Yong Kim, In‐Kyung Jeong, Cheol‐Young Park, Kun‐Ho Yoon, So Hun Kim, Bong‐Soo Cha
Diabetes, Obesity and Metabolism.2026; 28(1): 728. CrossRef
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Sang Min Yoon, Boyoung Park
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Original Articles

Diabetes, obesity and metabolism
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; Endocrinol Metab. 2025;40(1):112-124. Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2164

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Background
Data on the carcinogenic potential of tirzepatide from randomized controlled trials (RCTs) are limited. Furthermore, no meta-analysis has included all relevant RCTs to assess the cancer risk associated with tirzepatide.
Methods
RCTs involving patients receiving tirzepatide in the intervention arm and either a placebo or any active comparator in the control arm were searched through electronic databases. The primary outcome was the overall risk of any cancer, and secondary outcomes were the risks of specific types of cancer in the tirzepatide versus the control groups.
Results
Thirteen RCTs with 13,761 participants were analyzed. Over 26 to 72 weeks, the tirzepatide and pooled control groups had identical risks of any cancer (risk ratio, 0.78; 95% confidence interval, 0.53 to 1.16; P=0.22). The two groups had comparable cancer risks in patients with and without diabetes. In subgroup analyses, the risks were also similar in the tirzepatide versus placebo, insulin, and glucagon-like peptide-1 receptor agonist groups. The overall cancer risk was also comparable for different doses of tirzepatide compared to the control groups; only a 10-mg tirzepatide dose had a lower risk of any cancer than placebo. Furthermore, compared to the control groups (pooled or separately), tirzepatide did not increase the risk of any specific cancer types. Despite greater increments in serum calcitonin with 10- and 15-mg tirzepatide doses than with placebo, the included RCTs reported no cases of papillary thyroid carcinoma.
Conclusion
Tirzepatide use in RCTs over 26 to 72 weeks did not increase overall or specific cancer risk.

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Ping-Tao Tseng, Bing-Yan Zeng, Chih-Wei Hsu, Cheuk-Kwan Sun, Mein-Woei Suen, Andre F. Carvalho, Brendon Stubbs, Yen-Wen Chen, Tien-Yu Chen, Wei-Te Lei, Po-Huang Chen, Jiann-Jy Chen, Yow-Ling Shiue, Bing-Syuan Zeng, Kuan-Pin Su, Chih-Sung Liang
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Diabetes, obesity and metabolism
Effectiveness and Safety of Oral Quadruple Combination Therapy in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis: Jaehyun Bae, Min Heui Yu, Minyoung Lee, Bong-Soo Cha, Byung-Wan Lee; Endocrinol Metab. 2025;40(2):258-267. Published online January 13, 2025; DOI: https://doi.org/10.3803/EnM.2024.2120

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Background
Achieving optimal glucose control is essential in the management of type 2 diabetes (T2D). This study aimed to evaluate the effectiveness and safety of oral quadruple combination therapy for the treatment of T2D.
Methods
This meta-analysis reviewed original research on oral quadruple combination therapy for T2D, including both experimental and observational studies with a minimum duration of 12 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to follow-up. The secondary endpoint was the incidence rate of adverse events. Two investigators independently extracted data and assessed the risk of bias. Outcomes were pooled as the standardized mean difference (using Hedge’s g) and the risk ratio for adverse events in random-effects meta-analyses.
Results
The meta-analysis included 17 studies. Oral quadruple combination therapy resulted in an additional mean reduction in HbA1c levels of 1.1% in patients who did not achieve glycemic control with oral triple combination therapy. Compared with switching to injectables, such as insulin or a glucagon-like peptide-1 receptor agonist–containing regimen, this therapy was non-inferior, even demonstrating a slightly superior glucose-lowering effect. Furthermore, it was determined to be safe, with an adverse event rate of 0.25, indicating no significant difference in safety compared with adding a placebo or switching to an injectable-containing regimen.
Conclusion
Oral quadruple combination therapy is a valid option for patients with T2D who are unable to achieve glycemic targets with oral triple combination therapy, offering both effective glycemic control and a favorable safety profile.

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2025 Clinical Practice Guidelines for Diabetes Management in Korea: Recommendation of the Korean Diabetes Association
Shinae Kang, Seon Mee Kang, Jong Han Choi, Seung-Hyun Ko, Bo Kyung Koo, Hyuk-Sang Kwon, Mi Kyung Kim, Sang Yong Kim, Soo-Kyung Kim, Young-eun Kim, Eun Sook Kim, Jae Hyeon Kim, Chong Hwa Kim, Ji Min Kim, Hae Jin Kim, Min Kyong Moon, Sun Joon Moon, Jun Sung
Diabetes & Metabolism Journal.2025; 49(4): 582. CrossRef
Synergism of Synthetic Sulfonamides and Natural Antioxidants for the Management of Diabetes Mellitus Associated with Oxidative Stress
Ancuța Dinu (Iacob), Luminita-Georgeta Confederat, Ionut Dragostin, Ionela Daniela Morariu, Dana Tutunaru, Oana-Maria Dragostin
Current Issues in Molecular Biology.2025; 47(9): 709. CrossRef
2025 Clinical Practice Guidelines for Diabetes: Pharmacological Treatment of Type 2 Diabetes
Jong Han Choi
The Journal of Korean Diabetes.2025; 26(3): 158. CrossRef
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

Brief Report

Diabetes, obesity and metabolism
Metabolic Consequences of Glucagon-Like Peptide-1 Receptor Agonist Shortage: Deterioration of Glycemic Control in Type 2 Diabetes: Hun Jee Choe, Michael A. Nauck, Joon Ho Moon; Endocrinol Metab. 2025;40(1):156-160. Published online November 25, 2024; DOI: https://doi.org/10.3803/EnM.2024.2150

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In the context of a global shortage of glucagon-like peptide-1 (GLP-1) receptor agonists, we assessed the impact of discontinuing dulaglutide on metabolic control in individuals with type 2 diabetes. Our analysis included data from 69 individuals and revealed a significant deterioration in glycemic control following the discontinuation. Specifically, the average hemoglobin A1c level increased from 7.0%±0.9% to 8.1%±1.4% (P<0.001), and fasting glucose levels rose from 129±31 to 156±50 mg/dL (P<0.001) within 3 months after stopping the medication. Alternative treatments such as dipeptidyl peptidase-4 inhibitors and sodium glucose cotransporter- 2 inhibitors were insufficient substitutes, highlighting the essential role of continuous GLP-1 receptor agonist therapy in maintaining metabolic health.

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Velimir Altabas, Zrinka Orlović, Maja Baretić
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Kornela Kotucha, Katarzyna Kapłon, Magdalena Moś, Jakub Fiegler-Rudol, Alina Pietryszyn-Bilińska, Klaudia Dynarowicz, David Aebisher, Rafał Wiench, Aleksandra Kawczyk-Krupka
European Journal of Clinical and Experimental Medicine.2025;[Epub] CrossRef

Original Articles

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Risk of Diabetes Mellitus in Adults with Intellectual Disabilities: A Nationwide Cohort Study: Hye Yeon Koo, In Young Cho, Yoo Jin Um, Yong-Moon Mark Park, Kyung Mee Kim, Chung Eun Lee, Kyungdo Han; Endocrinol Metab. 2025;40(1):103-111. Published online November 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.2126

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Abstract PDF Supplementary Material PubReader ePub: Background
Intellectual disability (ID) may be associated with an increased risk of diabetes mellitus (DM). However, evidence from longitudinal studies is scarce, particularly in Asian populations.
Methods
This retrospective cohort study used representative linked data from the Korea National Disability Registration System and the National Health Insurance Service database. Adults (≥20 years) who received a national health examination in 2009 (3,385 individuals with ID and 3,463,604 individuals without ID) were included and followed until 2020. ID was identified using legal registration information. Incident DM was defined by prescription records with relevant diagnostic codes. Multivariable-adjusted Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for DM risks in individuals with ID compared to those without ID.
Results
Over a mean follow-up of 9.8 years, incident DM occurred in 302 (8.9%) individuals with ID and 299,156 (8.4%) individuals without ID. Having ID was associated with increased DM risk (aHR, 1.38; 95% CI, 1.23 to 1.55). Sensitivity analysis confirmed a higher DM risk in individuals with ID (aHR, 1.39; 95% CI, 1.24 to 1.56) than those with other disabilities (aHR, 1.11; 95% CI, 1.10 to 1.13) or no disability (reference). Stratified analysis showed higher DM risk in non-hypertensive subjects (aHR, 1.63; 95% CI, 1.43 to 1.86) compared to hypertensive subjects (aHR, 1.00; 95% CI, 0.80 to 1.26; P for interaction <0.001).
Conclusion
Adults with ID have an increased risk of developing DM, highlighting the need for targeted public health strategies to promote DM prevention in this population.

Diabetes, obesity and metabolism
Importance of the Hemoglobin Glycation Index for Risk of Cardiovascular and Microvascular Complications and Mortality in Individuals with Type 2 Diabetes: Claudia Regina Lopes Cardoso, Nathalie Carvalho Leite, Gil Fernando Salles; Endocrinol Metab. 2024;39(5):732-747. Published online October 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.2001

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Background
This study investigated the prognostic importance of the hemoglobin glycation index (HGI) for macrovascular and microvascular outcomes, mortality, and hypoglycemia occurrence in a type 2 diabetes cohort and compared it to glycated hemoglobin (HbA1c).
Methods
Baseline and mean first-year HGI and HbA1c, and the variability thereof, were assessed in 687 individuals with type 2 diabetes (median follow-up, 10.6 years). Multivariable Cox regression was conducted to evaluate the associations of HGI and HbA1c parameters with macrovascular (total and major cardiovascular events) and microvascular outcomes (microalbuminuria, advanced renal failure, retinopathy, and peripheral neuropathy), mortality (all-cause and cardiovascular), and moderate/severe hypoglycemia occurrence.
Results
During follow-up, there were 215 total cardiovascular events (176 major) and 269 all-cause deaths (131 cardiovascular). Microalbuminuria developed in 126 patients, renal failure in 104, retinopathy in 161, and neuropathy in 177. There were 90 hypoglycemia episodes. Both HGI and HbA1c predicted all adverse outcomes, except microalbuminuria and hypoglycemia. Their adjusted risks were roughly equivalent for all outcomes. For example, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), estimated for 1 standard deviation increments, of mean first-year HGI were 1.23 (1.05 to 1.44), 1.20 (1.03 to 1.38), 1.36 (1.11 to 1.67), 1.28 (1.09 to 1.67), and 1.29 (1.09 to 1.54), respectively, for cardiovascular events, all-cause mortality, renal failure, retinopathy, and neuropathy; whereas the respective HRs (95% CIs) of mean HbA1c were 1.31 (1.12 to 1.53), 1.28 (1.11 to 1.48), 1.36 (1.11 to 1.67), 1.33 (1.14 to 1.55), and 1.29 (1.09 to 1.53).
Conclusion
HGI was no better than HbA1c as a predictor of adverse outcomes in individuals with type 2 diabetes, and its clinical use cannot be currently advised.

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Fan Zhang, Rui Zhou, Yan Bai, Liuyan Huang, Jiao Li, Yifei Zhong
Diabetes Research and Clinical Practice.2025; 222: 112054. CrossRef
Association of hemoglobin glycation index and diabetic retinopathy results from NHANES
Ning Feng, Guang-Jie Cheng, Shun-Feng Zhao, Lin-Jun Du, Ning Guo, Na Zhang
International Journal of Diabetes in Developing Countries.2025;[Epub] CrossRef
Association Between the Hemoglobin Glycation Index (HGI) and Risk of Diabetic Nephropathy: A Retrospective Cohort Study
Weiyi Zhou, Lingyu Zhang, Tongqiang Liu
Diabetes, Metabolic Syndrome and Obesity.2025; Volume 18: 1859. CrossRef
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Yue Lv, Lingchen Wei, Ziyue Wang, Zichuan Mu, Jianlin Wu, Fuad Abdu,
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Frontiers in Endocrinology.2025;[Epub] CrossRef
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Review Article

Diabetes, obesity and metabolism
Changes in the Epidemiological Landscape of Diabetes in South Korea: Trends in Prevalence, Incidence, and Healthcare Expenditures: Kyoung Hwa Ha, Dae Jung Kim; Endocrinol Metab. 2024;39(5):669-677. Published online September 25, 2024; DOI: https://doi.org/10.3803/EnM.2024.2073

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Diabetes is a serious public health concern that significantly contributes to the global burden of disease. In Korea, the prevalence of diabetes is 12.5% among individuals aged 19 and older, and 14.8% among individuals aged 30 and older as of 2022. The total number of people with diabetes among those aged 19 and older is estimated to be 5.4 million. The incidence of diabetes decreased from 8.1 per 1,000 persons in 2006 to 6.3 per 1,000 persons in 2014, before rising again to 7.5 per 1,000 persons in 2019. Meanwhile, the incidence of type 1 diabetes increased significantly, from 1.1 per 100,000 persons in 1995 to 4.8 per 100,000 persons in 2016, with the prevalence reaching 41.0 per 100,000 persons in 2017. Additionally, the prevalence of gestational diabetes saw a substantial rise from 4.1% in 2007 to 22.3% in 2023. These changes have resulted in increases in the total medical costs for diabetes, covering both outpatient and inpatient services. Therefore, effective diabetes prevention strategies are urgently needed.

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Kyoung Hwa Ha, Soyoung Shin, EunJi Na, Dae Jung Kim
Journal of Diabetes Investigation.2025; 16(2): 215. CrossRef
Effects of Black Cumin Seed Extract on Pancreatic Islet β-Cell Proliferation and Hypoglycemic Activity in Streptozotocin-Induced Diabetic Rats
Jongkyu Kim, Yoon-Seok Chun, Namkyu Yoon, Byungkwon Kim, Kiin Choi, Sae-Kwang Ku, Namju Lee
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Kyuho Kim, Bongseong Kim, Kyuna Lee, Yu-Bae Ahn, Seung-Hyun Ko, Sung Hee Choi, Kyungdo Han, Jae-Seung Yun
Diabetes & Metabolism Journal.2025; 49(2): 183. CrossRef
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Kyoung Hwa Ha, Dae Jung Kim
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Original Article

Diabetes, obesity and metabolism
Impact of Chronic Kidney Disease and Gout on End-Stage Renal Disease in Type 2 Diabetes: Population-Based Cohort Study: Inha Jung, Da Young Lee, Seung Min Chung, So Young Park, Ji Hee Yu, Jun Sung Moon, Ji A Seo, Kyungdo Han, Nan Hee Kim; Endocrinol Metab. 2024;39(5):748-757. Published online August 30, 2024; DOI: https://doi.org/10.3803/EnM.2024.2020

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Background
We examined the impact of gout on the end-stage renal disease (ESRD) risk in patients with type 2 diabetes mellitus (T2DM) and determined whether this association differs according to chronic kidney disease (CKD) status.
Methods
Using the Korean National Health Insurance Service, this nationwide cohort study enrolled 847,884 patients with T2DM who underwent health checkups in 2009. Based on the presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m²) and gout (two outpatient visits or one hospitalization within 5 years), patients were classified into four groups: CKD⁻Gout⁻, CKD⁻ Gout⁺, CKD⁺Gout⁻, and CKD⁺Gout⁺. Patients with incident ESRD were followed up until December 2018.
Results
Among 847,884 patients, 11,825 (1.4%) experienced progression to ESRD. ESRD incidence increased in the following order: 0.77 per 1,000 person-years (PY) in the CKD⁻Gout⁻ group, 1.34/1,000 PY in the CKD⁻Gout⁺ group, 8.20/1,000 PY in the CKD⁺Gout⁻ group, and 23.06/1,000 PY in the CKD⁺Gout⁺ group. The presence of gout modified the ESRD risk in a status-dependent manner. Hazard ratios (HR) were 1.49 (95% confidence interval [CI], 1.32 to 1.69) and 2.24 (95% CI, 2.09 to 2.40) in patients without and with CKD, respectively, indicating a significant interaction (P<0.0001). The CKD⁺Gout⁺ group had a markedly higher risk of developing ESRD (HR, 18.9; 95% CI, 17.58 to 20.32) than the reference group (CKD⁻Gout⁻).
Conclusion
Gout substantially enhances the risk of ESRD, even in the absence of CKD. Concurrent CKD and gout synergistically increase the risk of ESRD. Therefore, physicians should carefully screen for hyperuricemia to prevent progression to ESRD.

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Heterogeneity in the development of diabetes-related complications: narrative review of the roles of ancestry and geographical determinants
Andrea O. Y. Luk, Yingnan Fan, Baoqi Fan, Edith W. K. Chow, Tony C. K. O
Diabetologia.2025; 68(11): 2386. CrossRef
Relationship between the Chinese visceral adiposity index and gout in individuals with type 2 diabetes mellitus: a cross-sectional population-based study
Ningyu Cai, Mengdie Chen, Ping Feng, Yiyun Wang, Xianping Zhu, Qidong Zheng
Frontiers in Nutrition.2025;[Epub] CrossRef

Brief Report

Diabetes, obesity and metabolism
Impact of Diabetes on COVID-19 Susceptibility: A Nationwide Propensity Score Matching Study: Han Na Jang, Sun Joon Moon, Jin Hyung Jung, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2024;39(5):813-818. Published online August 28, 2024; DOI: https://doi.org/10.3803/EnM.2024.2014

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Abstract PDF Supplementary Material PubReader ePub: Prior research has highlighted poor clinical outcomes in coronavirus disease 2019 (COVID-19)-infected patients with diabetes; however, susceptibility to COVID-19 infection in patients with diabetes has not been extensively studied. Participants aged ≥30 years who underwent COVID-19 testing from December 2019 to April 2020 were analyzed using the National Health Insurance Service data in South Korea. In a cohort comprising 29,433 1:1 propensity score-matched participants, COVID-19 positivity was significantly higher in participants with diabetes than in those without diabetes (512 [3.5%] vs. 395 [2.7%], P<0.001). Logistic regression analysis indicated that diabetes significantly increased the risk of COVID-19 test positivity (odds ratio, 1.307; 95% confidence interval, 1.144 to 1.493; P<0.001). Patients with diabetes exhibited heightened COVID-19 infection rates compared to individuals without diabetes, and diabetes increased the susceptibility to COVID-19, reinforcing the need for heightened preventive measures, particularly considering the poor clinical outcomes in this group.

Original Articles

Diabetes, obesity and metabolism
Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE): Nam Hoon Kim, Juneyoung Lee, Suk Chon, Jae Myung Yu, In-Kyung Jeong, Soo Lim, Won Jun Kim, Keeho Song, Ho Chan Cho, Hea Min Yu, Kyoung-Ah Kim, Sang Soo Kim, Soon Hee Lee, Chong Hwa Kim, Soo Heon Kwak, Yong‐ho Lee, Choon Hee Chung, Sihoon Lee, Heung Yong Jin, Jae Hyuk Lee, Gwanpyo Koh, Sang-Yong Kim, Jaetaek Kim, Ju Hee Lee, Tae Nyun Kim, Hyun Jeong Jeon, Ji Hyun Lee, Jae-Han Jeon, Hye Jin Yoo, Hee Kyung Kim, Hyeong-Kyu Park, Il Seong Nam-Goong, Seongbin Hong, Chul Woo Ahn, Ji Hee Yu, Jong Heon Park, Keun-Gyu Park, Chan Ho Park, Kyong Hye Joung, Ohk-Hyun Ryu, Keun Yong Park, Eun-Gyoung Hong, Bong-Soo Cha, Kyu Chang Won, Yoon-Sok Chung, Sin Gon Kim; Endocrinol Metab. 2024;39(5):722-731. Published online August 22, 2024; DOI: https://doi.org/10.3803/EnM.2024.1995

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Background
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

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Ezetimibe attenuates diabetic retinopathy via NRF2-mediated suppression of inflammation and oxidative stress
Lei Cheng, Shan Cheng, Ran Zhu, Guoxu Xu
Journal of Diabetes and its Complications.2026; 40(2): 109250. CrossRef
Current and Emerging Treatment Options for Hypertriglyceridemia: State-of-the-Art Review
Jakub Michal Zimodro, Manfredi Rizzo, Ioanna Gouni-Berthold
Pharmaceuticals.2025; 18(2): 147. CrossRef
Fenofibrate therapy and risk of heart failure outcomes in patients with Type 2 diabetes: a propensity-matched cohort study
Ji Yoon Kim, Nam Hoon Kim, Jiyoon Lee, Dong-Hoon Kim, Sin Gon Kim
European Heart Journal - Cardiovascular Pharmacotherapy.2025; 11(7): 620. CrossRef
Beyond lipids: fenofibrate in diabetic retinopathy and nephropathy
Mengying Liu, Seok Ting Lim, Weihua Song, Thomas M. Coffman, Xiaomeng Wang
Trends in Pharmacological Sciences.2025;[Epub] CrossRef
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Pitchai Balakumar, Sultan Alshahrani, Noohu Abdulla Khan, Rajavel Varatharajan, K. M. Sundram
Journal of Applied Toxicology.2025;[Epub] CrossRef

Diabetes, obesity and metabolism
Amelioration of Insulin Resistance after Delivery Is Associated with Reduced Risk of Postpartum Diabetes in Women with Gestational Diabetes Mellitus: Heejun Son, Joon Ho Moon, Sung Hee Choi, Nam H. Cho, Soo Heon Kwak, Hak Chul Jang; Endocrinol Metab. 2024;39(5):701-710. Published online August 21, 2024; DOI: https://doi.org/10.3803/EnM.2024.1974

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Background
Identifying risk factors for postpartum type 2 diabetes in women with gestational diabetes mellitus (GDM) is crucial for effective interventions. We examined whether changes in insulin sensitivity after delivery affects the risk of type 2 diabetes in women with GDM.
Methods
This prospective cohort study included 347 women with GDM or gestational impaired glucose tolerance, who attended the follow-up visits at 2 months postpartum and annually thereafter. Changes in insulin sensitivity were calculated using the Matsuda index at GDM diagnosis and at 2 months postpartum (ΔMatsuda index). After excluding women with pregestational diabetes or those followed up only once, we analyzed the risk of postpartum type 2 diabetes based on the ΔMatsuda index tertiles.
Results
The incidence of type 2 diabetes at the two-month postpartum visit decreased with increasing ΔMatsuda index tertiles (16.4%, 9.5%, and 1.8%, P=0.001). During a 4.1-year follow-up, 26 out of 230 women who attended more than two follow-up visits (11.3%) developed type 2 diabetes. Compared to the lowest tertile, subjects in the highest ΔMatsuda index tertile showed a significantly reduced risk of type 2 diabetes (hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.93; P=0.036) after adjusting for confounders.
Conclusion
Improvement in insulin sensitivity after delivery is associated with a reduced risk of postpartum type 2 diabetes in women with GDM. Postpartum changes in insulin sensitivity could be a useful prediction for future type 2 diabetes development in women with GDM.

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Gestational Diabetes Mellitus: Mechanisms Underlying Maternal and Fetal Complications
Jooyeop Lee, Na Keum Lee, Joon Ho Moon
Endocrinology and Metabolism.2025; 40(1): 10. CrossRef
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Karolina Karcz, Paulina Gaweł, Barbara Królak-Olejnik
Nutrients.2024; 16(22): 3871. CrossRef

Diabetes, obesity and metabolism
Financial Benefits of Renal Dose-Adjusted Dipeptidyl Peptidase-4 Inhibitors for Patients with Type 2 Diabetes and Chronic Kidney Disease: Hun Jee Choe, Yeh-Hee Ko, Sun Joon Moon, Chang Ho Ahn, Kyoung Hwa Ha, Hyeongsuk Lee, Jae Hyun Bae, Hyung Joon Joo, Hyejin Lee, Jang Wook Son, Dae Jung Kim, Sin Gon Kim, Kwangsoo Kim, Young Min Cho; Endocrinol Metab. 2024;39(4):622-631. Published online August 1, 2024; DOI: https://doi.org/10.3803/EnM.2024.1965

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Abstract PDF Supplementary Material PubReader ePub: Background
Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes.
Methods
This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models.
Results
In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of ≥60, <60, <45, and <30 mL/min/1.73 m², respectively). When model 1 was applied, the cost savings per year were 7.6% for eGFR <60 mL/min/1.73 m² and 30.4% for eGFR <30 mL/min/1.73 m². According to model 2, 15.4% to 51.2% per year could be saved depending on kidney impairment severity.
Conclusion
Adjusting the doses of RDA DPP4 inhibitors based on individual kidney function could alleviate the economic burden associated with medical expenses.

Brief Report

Diabetes, obesity and metabolism
Ketonuria as an Indicator of Improvement of Renal Function in Patients with Type 2 Diabetes Receiving SGLT2 Inhibitor Treatment: Hyun Ah Kim, Han Na Jang, Sung Hye Kong, Young Lee, Sung Hee Choi, Young Min Cho, Hak Chul Jang, Tae Jung Oh; Endocrinol Metab. 2024;39(4):653-658. Published online May 16, 2024; DOI: https://doi.org/10.3803/EnM.2024.1919

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We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, –0.02 mL/min/1.73 m² [95% confidence interval (CI), –3.87 to 3.83 mL/min/1.73 m²] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m² [95% CI, 3.16 to 10.46 mL/min/1.73 m²]; P<0.001). Improvement in estimated glomerular filtration rate at 6 months was associated with female sex and lower baseline body weight, blood pressure, and triglyceride levels in patients with ketonuria. In conclusion, the presence of ketonuria was associated with the renoprotective effect of SGLT2 inhibitors, and female sex and the absence of metabolic syndrome components may serve as additional indicators of these medications’ substantial renoprotective effects in individuals with ketonuria.

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Effects of a continuous remote care intervention including nutritional ketosis on kidney function and inflammation in adults with type 2 diabetes: a post-hoc latent class trajectory analysis
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Seung Wan Noh, Han Sol Ryu, Yong-Ho Kim, Byung-Chul Oh
Endocrinology and Metabolism.2025; 40(6): 851. CrossRef
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Review Articles

Diabetes, obesity and metabolism
Scaling Insulin-Producing Cells by Multiple Strategies: Jinhyuk Choi, Fritz Cayabyab, Harvey Perez, Eiji Yoshihara; Endocrinol Metab. 2024;39(2):191-205. Published online April 4, 2024; DOI: https://doi.org/10.3803/EnM.2023.1910

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In the quest to combat insulin-dependent diabetes mellitus (IDDM), allogenic pancreatic islet cell therapy sourced from deceased donors represents a significant therapeutic advance. However, the applicability of this approach is hampered by donor scarcity and the demand for sustained immunosuppression. Human induced pluripotent stem cells are a game-changing resource for generating synthetic functional insulin-producing β cells. In addition, novel methodologies allow the direct expansion of pancreatic progenitors and mature β cells, thereby circumventing prolonged differentiation. Nevertheless, achieving practical reproducibility and scalability presents a substantial challenge for this technology. As these innovative approaches become more prominent, it is crucial to thoroughly evaluate existing expansion techniques with an emphasis on their optimization and scalability. This manuscript delineates these cutting-edge advancements, offers a critical analysis of the prevailing strategies, and underscores pivotal challenges, including cost-efficiency and logistical issues. Our insights provide a roadmap, elucidating both the promises and the imperatives in harnessing the potential of these cellular therapies for IDDM.

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Diabetes, obesity and metabolism
Glucocorticoid-Induced Hyperglycemia: A Neglected Problem: Jung-Hwan Cho, Sunghwan Suh; Endocrinol Metab. 2024;39(2):222-238. Published online March 27, 2024; DOI: https://doi.org/10.3803/EnM.2024.1951

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Glucocorticoids provide a potent therapeutic response and are widely used to treat a variety of diseases, including coronavirus disease 2019 (COVID-19) infection. However, the issue of glucocorticoid-induced hyperglycemia (GIH), which is observed in over one-third of patients treated with glucocorticoids, is often neglected. To improve the clinical course and prognosis of diseases that necessitate glucocorticoid therapy, proper management of GIH is essential. The key pathophysiology of GIH includes systemic insulin resistance, which exacerbates hepatic steatosis and visceral obesity, as well as proteolysis and lipolysis of muscle and adipose tissue, coupled with β-cell dysfunction. For patients on glucocorticoid therapy, risk stratification should be conducted through a detailed baseline evaluation, and frequent glucose monitoring is recommended to detect the onset of GIH, particularly in high-risk individuals. Patients with confirmed GIH who require treatment should follow an insulin-centered regimen that varies depending on whether they are inpatients or outpatients, as well as the type and dosage of glucocorticoid used. The ideal strategy to maintain normoglycemia while preventing hypoglycemia is to combine basal-bolus insulin and correction doses with a continuous glucose monitoring system. This review focuses on the current understanding and latest evidence concerning GIH, incorporating insights gained from the COVID-19 pandemic.

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Original Article

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

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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
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.2025; 31(4): 471. 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.2025; 31(5): 703. 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
Effect of beinaglutide, a thrice-daily GLP-1 receptor agonist, on body weight and metabolic parameters: A systematic review and meta-analysis
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Review Article

Adrenal gland
The Fascinating Interplay between Growth Hormone, Insulin-Like Growth Factor-1, and Insulin: Eline C. Nijenhuis-Noort, Kirsten A. Berk, Sebastian J. C. M. M. Neggers, Aart J. van der Lely; Endocrinol Metab. 2024;39(1):83-89. Published online January 9, 2024; DOI: https://doi.org/10.3803/EnM.2024.101

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This review intends to provide the reader with a practical overview of several (patho)physiological conditions in which knowledge of the interplay between growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin is important. This might help treating physicians in making the right decisions on how to intervene and improve metabolism for the benefit of patients, and to understand why and how metabolism responds in their specific cases. We will specifically address the interplay between GH, IGF-1, and insulin in type 1 and 2 diabetes mellitus, liver cirrhosis, and acromegaly as examples in which this knowledge is truly necessary.

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Original Articles

Diabetes, obesity and metabolism
Effectiveness of a Social Networking Site Based Automatic Mobile Message Providing System on Glycemic Control in Patients with Type 2 Diabetes Mellitus: Kyuho Kim, Jae-Seung Yun, Joonyub Lee, Yeoree Yang, Minhan Lee, Yu-Bae Ahn, Jae Hyoung Cho, Seung-Hyun Ko; Endocrinol Metab. 2024;39(2):344-352. Published online December 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1871

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Background
This study investigated the effectiveness of a social networking site (SNS)-based automatic mobile message providing system on glycemic control in patients with type 2 diabetes mellitus (T2DM).
Methods
A 3-month, randomized, open-label, controlled, parallel-group trial was conducted. One hundred and ten participants with T2DM were randomized to a mobile message system (MMS) (n=55) or control group (n=55). The MMS group received protocolbased automated messages two times per day for 10 weeks regarding diabetes self-management through KakaoTalk SNS messenger. The primary outcome was the difference in the change in glycated hemoglobin (HbA1c) levels (%) from baseline to week 12.
Results
HbA1c levels were more markedly decreased in the MMS group (8.4%±0.7% to 8.0%±1.1%) than in the control group (8.5%±0.8% to 8.4%±0.8%), resulting in a significant between-group difference (P=0.027). No differences were observed in changes in fasting glucose levels, lipid profiles, and the number of participants who experienced hypoglycemia, or in changes in lifestyle behavior between groups. However, the self-monitoring of blood glucose frequency was significantly increased in the MMS group compared to the control group (P=0.003). In addition, sleep duration was increased in the MMS group, but was not changed in the control group.
Conclusion
An SNS-based automatic mobile message providing system was effective in improving glycemic control in patients in T2DM. Studies which based on a more individualized protocol, and investigate longer beneficial effect and sustainability will be required in the future.

Citations

Citations to this article as recorded by

Text messaging interventions are associated with reductions in HbA1c among patients with diabetes: a systematic review and meta-analysis
Neda Pirouzmand, Grace S Ko, Lucas C Godoy, Olivia Haldenby, Cynthia A Jackevicius, Ayman Jubran, Candace D McNaughton, Baiju R Shah, Maneesh Sud, Karen Tu, Dennis T Ko
BMJ Open Diabetes Research & Care.2025; 13(6): e005218. CrossRef
Effectiveness of text message-delivered health behaviour intervention on HbA1c change in adults with type 2 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials
Qiumian Hong, Xiaoying Zhang, Mengxi Guo, Zhaoyang Wen, Qing Tang, Jiali Zhou, Peige Song, Xiaolin Wei, Ning Zhang
Health Psychology Review.2025; : 1. CrossRef
Effects of multimodal mobile health interventions on cardiovascular risk factor management in patients with diabetes: a systematic review and meta-analysis
Yan Zhang, Xingqi Cao, LiJuan Huang, Yue Zhu, Liying Chen
BMJ Open.2025; 15(12): e108371. CrossRef

Mineral, Bone & Muscle Big Data Articles (National Health Insurance Service Database)
Association between Smoking Status and the Risk of Hip Fracture in Patients with Type 2 Diabetes: A Nationwide Population-Based Study: Se-Won Lee, Jun-Young Heu, Ju-Yeong Kim, Jinyoung Kim, Kyungdo Han, Hyuk-Sang Kwon; Endocrinol Metab. 2023;38(6):679-689. Published online December 6, 2023; DOI: https://doi.org/10.3803/EnM.2023.1760

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Background
Limited longitudinal evidence exists regarding the potential association between smoking status and hip fracture among individuals with type 2 diabetes. We investigated this association using large-scale, nationwide cohort data for the Korean population.
Methods
This nationwide cohort study included 1,414,635 adults aged 40 and older who received Korean National Health Insurance Service health examinations between 2009 and 2012. Subjects with type 2 diabetes were categorized according to their smoking status, amount smoked (pack-years), number of cigarettes smoked per day, and duration of smoking. The results are presented as hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between smoking status parameters and risk of hip fracture in multivariable Cox proportional hazard regression analysis.
Results
Compared with never-smokers, an increased adjusted HR (aHR) for hip fracture was observed in current smokers (1.681; 95% CI, 1.578 to 1.791), and a comparable aHR for hip fracture was found in former smokers (1.065; 95% CI, 0.999 to 1.136). For former smokers who had smoked 20 pack-years or more, the risk was slightly higher than that for never-smokers (aHR, 1.107; 95% CI, 1.024 to 1.196). The hip fracture risk of female former smokers was similar to that of female current smokers, but the hip fracture risk in male former smokers was similar to that of male never-smokers.
Conclusion
Smoking is associated with an increased risk of hip fracture in patients with type 2 diabetes. Current smokers with diabetes should be encouraged to quit smoking because the risk of hip fracture is greatly reduced in former smokers.

Citations

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Hip fractures and type 2 diabetes in the elderly: Risk factors analysis of the Nedices cohort
Federico Hawkins Carranza, Cristina Martín-Arriscado Arroba, Arturo Corbatón-Anchuelo, Guillermo Martínez Díaz-Guerra, Félix Bermejo Pareja
Diabetes & Metabolism.2025; 51(4): 101656. CrossRef
Bone Health in Type 1 and Type 2 Diabetes: Pathophysiological Mechanisms, Clinical Implications, and Management Strategies
Hermine Carine Pouabe Epse Bodah, Suraiya Rahman Shifa, Sara Saleh, Tuba Abeer Hashmi, Tuleen Al Shawa, Badreshiya Kajal Akshaykumar, Nabeel Sufwan, Rajvinder Kaur, Andrii Shevchuk, Usman Ul Haq, Manju Rai
SN Comprehensive Clinical Medicine.2025;[Epub] CrossRef
Influence of quitting smoking on diabetes-related complications: A scoping review with a systematic search strategy
Magdalena Walicka, Arkadiusz Krysiński, Giusy Rita Maria La Rosa, Ang Sun, Davide Campagna, Agostino Di Ciaula, Tabinda Dugal, Andre Kengne, Phuong Le Dinh, Anoop Misra, Riccardo Polosa, Syed Abbas Raza, Cristina Russo, Roberta Sammut, Noel Somasundaram
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2024; 18(5): 103044. CrossRef

Review Articles

Diabetes, obesity and metabolism
Initial Combination Therapy in Type 2 Diabetes: Ji Yoon Kim, Nam Hoon Kim; Endocrinol Metab. 2024;39(1):23-32. Published online November 30, 2023; DOI: https://doi.org/10.3803/EnM.2023.1816

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Type 2 diabetes (T2D) is a progressive disease in which it is challenging to achieve long-term durable glycemic control. However, intensive glycemic control is crucial for preventing diabetes-related complications. Previous studies showed that monotherapy with a stepwise add-on approach was seldom effective for long-term durable glycemic control. Combination therapy, which refers to the use of two or more drugs to control hyperglycemia, has multiple benefits, including the ability to target a variety of pathophysiological processes underlying hyperglycemia. In clinical trials, initial combination therapy showed better glycemic control than monotherapy or a stepwise approach. Emerging evidence indicates that initial combination therapy is associated with preserved β-cell function and fewer complications in T2D. However, cost-effectiveness and adverse events with combination therapy are issues that should be considered. Therefore, initial combination therapy is an important option for patients with T2D that clinicians should consider with a view toward balancing benefits and potential harms. In this review, we summarize the literature addressing initial combination therapy in T2D, and we suggest optimal strategies based on clinical situations and patient characteristics.

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Glycemia Risk Index is Associated With Risk of Albuminuria Among Individuals With Type 1 Diabetes
Ji Yoon Kim, Jee Hee Yoo, Nam Hoon Kim, Jae Hyeon Kim
Journal of Diabetes Science and Technology.2025;[Epub] CrossRef
Ginsenoside Rb1 and berberine synergistically protect against type 2 diabetes mellitus via GDF15/HAMP pathway throughout the liver lobules: Insights from spatial transcriptomics analysis
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Pharmacological Research.2025; 215: 107711. CrossRef
Factors associated with prescription of modern antidiabetics in newly diagnosed patients with type 2 diabetes. a real-world data study in a Spanish region
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Frontiers in Pharmacology.2025;[Epub] CrossRef
Fenofibrate therapy and risk of heart failure outcomes in patients with Type 2 diabetes: a propensity-matched cohort study
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European Heart Journal - Cardiovascular Pharmacotherapy.2025; 11(7): 620. CrossRef
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Amra Demirović, Alija Uzunović, Anisa Veledar-Hamalukić
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Results in Chemistry.2025; 18: 102830. CrossRef
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Diabetes & Metabolism Journal.2025; 49(6): 1287. CrossRef
Anti-Senescence Effect of Inhibiting Sodium-Glucose Cotransporter 2 and α-Glucosidase in a Type 2 Diabetes Mellitus Animal Model
Serin Hong, Byung Soo Kong, Hyunsuk Lee, Young Min Cho
Diabetes & Metabolism Journal.2025; 49(6): 1229. CrossRef
Targeting adipose remodeling: Synergistic mechanisms of drugs and adipose-derived stem cells in obese type 2 diabetes mellitus
Cheng Luo, Xian-Mei Yu, Liang-Yan Hua, Mei-Qi Zeng, Hui Xu, Cheng-Zheng Duan, Shi-Yu Xu, Da Sun, Li-Ya Ye, Dong-Juan He
World Journal of Stem Cells.2025;[Epub] CrossRef
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Ji Yoon Kim, Hye‐Min Jang, Hye‐Jin Lee, Ah Hyeon Lee, Dong‐Hoon Kim, Sin Gon Kim, Nam Hoon Kim
Diabetes, Obesity and Metabolism.2025;[Epub] CrossRef
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Abubakar Gapizov, Ahmad Mohammad, Shivam Singla, Bhavna Singla, Saifullah Syed, Sunita Kumawat, Zulqurnain Ali
Cureus.2025;[Epub] CrossRef
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Meditsinskiy sovet = Medical Council.2024; (16): 135. CrossRef

Miscellaneous
Toward Systems-Level Metabolic Analysis in Endocrine Disorders and Cancer: Aliya Lakhani, Da Hyun Kang, Yea Eun Kang, Junyoung O. Park; Endocrinol Metab. 2023;38(6):619-630. Published online November 21, 2023; DOI: https://doi.org/10.3803/EnM.2023.1814

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Metabolism is a dynamic network of biochemical reactions that support systemic homeostasis amidst changing nutritional, environmental, and physical activity factors. The circulatory system facilitates metabolite exchange among organs, while the endocrine system finely tunes metabolism through hormone release. Endocrine disorders like obesity, diabetes, and Cushing’s syndrome disrupt this balance, contributing to systemic inflammation and global health burdens. They accompany metabolic changes on multiple levels from molecular interactions to individual organs to the whole body. Understanding how metabolic fluxes relate to endocrine disorders illuminates the underlying dysregulation. Cancer is increasingly considered a systemic disorder because it not only affects cells in localized tumors but also the whole body, especially in metastasis. In tumorigenesis, cancer-specific mutations and nutrient availability in the tumor microenvironment reprogram cellular metabolism to meet increased energy and biosynthesis needs. Cancer cachexia results in metabolic changes to other organs like muscle, adipose tissue, and liver. This review explores the interplay between the endocrine system and systems-level metabolism in health and disease. We highlight metabolic fluxes in conditions like obesity, diabetes, Cushing’s syndrome, and cancers. Recent advances in metabolomics, fluxomics, and systems biology promise new insights into dynamic metabolism, offering potential biomarkers, therapeutic targets, and personalized medicine.

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Development and validation of an interpretable machine learning model for predicting intraoperative HDI in PPGL based on intratumoral and peritumoral CT radiomics
Shurong Li, Zhiqiang Zhang, Yubing Zhang, Yulong Chen, Jian Ling, Qingfen Hong, Xuanling Wu, Fufu Zheng, Cheng Luo
European Journal of Radiology.2026; 195: 112559. CrossRef
Factors Associated with the Development of Skin Lesions in Hospitalized Patients Admitted to a Nursing Preventive Care Program in Colombia
Gaby E. Escobar, Ángela F Espinosa, Olga L. Cortés, Nicolás Molano González
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Editorial: Tumor metabolism and programmed cell death
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Molecular subtypes of clear cell renal carcinoma based on PCD-related long non-coding RNAs expression: insights into the underlying mechanisms and therapeutic strategies
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Original Article

Miscellaneous
Prediction of Cardiovascular Complication in Patients with Newly Diagnosed Type 2 Diabetes Using an XGBoost/GRU-ODE-Bayes-Based Machine-Learning Algorithm: Joonyub Lee, Yera Choi, Taehoon Ko, Kanghyuck Lee, Juyoung Shin, Hun-Sung Kim; Endocrinol Metab. 2024;39(1):176-185. Published online November 21, 2023; DOI: https://doi.org/10.3803/EnM.2023.1739

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Background
Cardiovascular disease is life-threatening yet preventable for patients with type 2 diabetes mellitus (T2DM). Because each patient with T2DM has a different risk of developing cardiovascular complications, the accurate stratification of cardiovascular risk is critical. In this study, we proposed cardiovascular risk engines based on machine-learning algorithms for newly diagnosed T2DM patients in Korea.
Methods
To develop the machine-learning-based cardiovascular disease engines, we retrospectively analyzed 26,166 newly diagnosed T2DM patients who visited Seoul St. Mary’s Hospital between July 2009 and April 2019. To accurately measure diabetes-related cardiovascular events, we designed a buffer (1 year), an observation (1 year), and an outcome period (5 years). The entire dataset was split into training and testing sets in an 8:2 ratio, and this procedure was repeated 100 times. The area under the receiver operating characteristic curve (AUROC) was calculated by 10-fold cross-validation on the training dataset.
Results
The machine-learning-based risk engines (AUROC XGBoost=0.781±0.014 and AUROC gated recurrent unit [GRU]-ordinary differential equation [ODE]-Bayes=0.812±0.016) outperformed the conventional regression-based model (AUROC=0.723± 0.036).
Conclusion
GRU-ODE-Bayes-based cardiovascular risk engine is highly accurate, easily applicable, and can provide valuable information for the individualized treatment of Korean patients with newly diagnosed T2DM.

Citations

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A Novel Approach Utilizing Bagging, Histogram Gradient Boosting, and Advanced Feature Selection for Predicting the Onset of Cardiovascular Diseases
Norma Latif Fitriyani, Muhammad Syafrudin, Nur Chamidah, Marisa Rifada, Hendri Susilo, Dursun Aydin, Syifa Latif Qolbiyani, Seung Won Lee
Mathematics.2025; 13(13): 2194. CrossRef
Development and validation of a machine learning model for cardiovascular disease risk prediction in type 2 diabetes patients
Chunming Xu, Fachao Shi, Wenlong Ding, Cunming Fang, Caoyang Fang
Scientific Reports.2025;[Epub] CrossRef
Practice Primacy: Revisiting the Knowledge–Action Gap in Pro-Environmental Behavior with eXplainable AI
Xun Yang, Shensheng Chen, Tingting Liu, Junjie Luo, Yuzhen Tang
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Jieyun You, Tianwen Wei, Yue Yu, Jing Huang, Yuxiao Sun, Wei Guo, Qi Zhang
Frontiers in Medicine.2025;[Epub] CrossRef

Review Article

Diabetes, obesity and metabolism
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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The Use of Continuous Glucose Monitoring in Comparison to Self-Monitoring of Blood Glucose in Gestational Diabetes: A Systematic Review
Bhavadharini Balaji, Wesley Hannah, Polina V. Popova, Uma Ram, Mohan Deepa, Janeline Lunghar, Kumaran Uthra, Haritha Sagili, Sadishkumar Kamalanathan, Ranjit Mohan Anjana, Viswanathan Mohan
Journal of Diabetes Science and Technology.2026; 20(1): 173. CrossRef
Glucose circadian rhythm assessment in pregnant women for gestational diabetes screening
Rafael Bravo, Kyung Hyun Lee, Sarah A. Nazeer, Jocelyn A. Cornthwaite, Michal Fishel Bartal, Claudia Pedroza
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Quality of Life in Women With Gestational Diabetes Mellitus and Treatment Satisfaction Upon Intermittently Scanned Continuous Glucose Monitoring
Sookyung Won, Hyeon Ji Kim, Jee Yoon Park, Kyung Joon Oh, Sung Hee Choi, Hak Chul Jang, Joon Ho Moon
Journal of Korean Medical Science.2025;[Epub] CrossRef
Glucose time in range trajectories during pregnancy and association with adverse perinatal outcomes: a joint latent-class trajectory modeling approach
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Journal of Diabetes Science and Technology.2025;[Epub] CrossRef
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Michael Joubert, Benjamin Bouillet, Gaëtan Prevost, Bruno Vermesse, Helen Mosnier-Pudar, Jean-François Thébaut, Jean-Pierre Riveline, Noëlle Davoust, Bruno Guerci, Laurent Meyer
Médecine des Maladies Métaboliques.2025; 19(4): 331. CrossRef
Continuous glucose monitoring system in diabetes in pregnancy: a narrative review
Melanie Rodacki, Marcio Krakauer, Denise Reis Franco, Patricia Medici Dualib, Mauro Sancovski, Lenita Zajdenverg
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Hee Sun Kang, Hyang Rang Park, Jangmi Kang, Chun-Ja Kim
The Science of Diabetes Self-Management and Care.2025; 51(6): 559. CrossRef
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Original Articles

Diabetes, obesity and metabolism
Coronary Artery Calcium Score as a Sensitive Indicator of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus: A Long-Term Cohort Study: Dae-Jeong Koo, Mi Yeon Lee, Sun Joon Moon, Hyemi Kwon, Sang Min Lee, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki Won Oh, Sung Rae Cho, Young-Hoon Jeong, Eun-Jung Rhee; Endocrinol Metab. 2023;38(5):568-577. Published online October 10, 2023; DOI: https://doi.org/10.3803/EnM.2023.1770

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Background
Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden.
Methods
We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease.
Results
The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100.
Conclusion
CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.

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Innovative Lipid-Lowering Strategies: RNA-Based, Small Molecule, and Protein-Based Therapies
Youngwoo Jang, Eun-Jung Rhee, Sung Hee Choi
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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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Diabetes, obesity and metabolism
Intake of Fruit and Glycemic Control in Korean Patients with Diabetes Mellitus Using the Korea National Health and Nutrition Examination Survey: Eunju Yoon, Ji Cheol Bae, Sunghwan Suh; Endocrinol Metab. 2023;38(5):538-544. Published online August 8, 2023; DOI: https://doi.org/10.3803/EnM.2023.1730

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Background
Despite the well-recognized health benefits of fresh fruit consumption, there is still substantial uncertainty about its potential effects on glycemic control in patients with type 2 diabetes mellitus (T2DM).
Methods
We examined the association of fresh fruit consumption and glycemic control in patients with T2DM using data from the 6th Korea National Health and Nutrition Examination Survey. The study sample was divided into three groups based on weekly fruit consumption frequency for the analysis.
Results
Patients with the highest fruit intake were older than those in the other two groups, and women were more likely to consume fruits in general. Being a current smoker and weekly alcohol intake also showed negative correlations according to the fruit intake tertiles. Fruit consumption was positively correlated with better hemoglobin A1c (HbA1c) levels. Moreover, patients in the highest tertile of fruit intake were 3.48 times more likely to be in good glycemic control defined as HbA1c <7%.
Conclusion
We observed that fruit consumption can be helpful in glycemic control in Korean patients with T2DM.

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Diabetes, obesity and metabolism
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; Endocrinol Metab. 2023;38(4):426-435. Published online July 20, 2023; DOI: https://doi.org/10.3803/EnM.2023.1737

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Background
The effects of dipeptidyl peptidase 4 (DPP-4) inhibitors over the course of long-term treatment remain unclear, and concerns have been raised regarding the role of DPP-4 inhibitors in carcinogenesis in the pancreas. Earlier studies of pancreatic adverse events have reported conflicting results.
Methods
This study analyzed Korean National Health Insurance Service data from January 2009 to December 2012. Patients who had type 2 diabetes mellitus and took two or more oral glucose-lowering drugs (GLDs) were included. Patients prescribed DPP-4 inhibitors (n=51,482) or other GLDs (n=51,482) were matched at a 1:1 ratio using propensity score matching. The risk of pancreatic cancer was calculated using Kaplan-Meier curves and Cox proportional-hazards regression analysis.
Results
During a median follow-up period of 7.95 years, 1,051 new cases of pancreatic cancer were identified. The adjusted hazard ratio (HR) for DPP-4 inhibitor use was 0.99 (95% confidence interval [CI], 0.88 to 1.12) compared with the other GLD group. In an analysis limited to cases diagnosed with pancreatic cancer during hospitalization, the adjusted HR for the use of DPP-4 inhibitors was 1.00 (95% CI, 0.86 to 1.17) compared with patients who took other GLDs. Using the other GLD group as the reference group, no trend was observed for elevated pancreatic cancer risk with increased DPP-4 inhibitor exposure.
Conclusion
In this population-based cohort study, DPP-4 inhibitor use over the course of relatively long-term follow-up showed no significant association with an elevated risk of pancreatic cancer.

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Diabetes, obesity and metabolism
Greater Severity of Steatosis Is Associated with a Higher Risk of Incident Diabetes: A Retrospective Longitudinal Study: Ji Min Han, Jung Hwan Cho, Hye In Kim, Sunghwan Suh, Yu-Ji Lee, Jung Won Lee, Kwang Min Kim, Ji Cheol Bae; Endocrinol Metab. 2023;38(4):418-425. Published online July 12, 2023; DOI: https://doi.org/10.3803/EnM.2023.1729

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Background
Fatty liver is associated with increased risk of developing type 2 diabetes. We aimed to evaluate whether the severity of hepatic steatosis is associated with incident diabetes.
Methods
We conducted a longitudinal analysis using data from 1,798 participants who underwent a comprehensive health checkup and abdominal computed tomography (CT). We assessed the association between baseline liver attenuation value on non-contrast CT images and risk of incident diabetes. All the participants were categorized into three groups based on the baseline liver attenuation value on non-contrast CT images: without hepatic steatosis (>57 Hounsfield unit [HU]), mild hepatic steatosis (41–57 HU), and moderate to severe hepatic steatosis (≤40 HU).
Results
During a median follow-up period of 5 years, 6.0% of the study participants progressed to diabetes. The incidence of diabetes was 17.3% in the moderate to severe hepatic steatosis group, 9.0% in the mild steatosis group, and 2.9% in those without hepatic steatosis. In a multivariate adjustment model, as compared with participants without hepatic steatosis, those with moderate to severe steatosis had a hazard ratio (HR) of 3.24 (95% confidence interval [CI], 1.64 to 4.2) for the development of diabetes, and those in the mild steatosis group had a HR of 2.33 (95% CI, 1.42 to 3.80). One standard deviation decrease in mean CT attenuation values of the liver was associated with a 40% increase in the development of diabetes (multivariate adjusted HR, 1.40; 95% CI, 1.2 to 1.63).
Conclusion
We found a positive association between severity of hepatic steatosis and risk of incident diabetes. Greater severity of steatosis was associated with a higher risk of incident diabetes.

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