Endocrinology and Metabolism

Original Article

Trends in Diabetes Mellitus Burden and Changes in Attributable Risk Factors in Asia from 1990 to 2021: Results from the Global Burden of Disease Study 2021: Xia Zhou, Mei Yang, Mei Xue, Yayun Li; Received October 28, 2025 Accepted February 25, 2026 Published online July 13, 2026; DOI: https://doi.org/10.3803/EnM.2025.2749 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The burden of diabetes mellitus (DM) in Asia has been increasing; however, systematic assessments of long-term incidence trends, subtype-specific differences, and modifiable risk factors remain limited. Using Global Burden of Disease Study 2021 data, we evaluated incidence trends in DM and its subtypes (type 1 diabetes mellitus [T1DM] and type 2 diabetes mellitus [T2DM]) in Asia from 1990 to 2021 and quantified the risk-attributable burden.
Methods
We analyzed the number of cases, age-standardized incidence rate (ASIR), estimated annual percentage change (EAPC), and risk-attributable age-standardized disability-adjusted life year rate (ASDR) for DM and its subtypes. Decomposition analysis was also performed to quantify the contributions of population growth, aging, and epidemiological changes to increases in case numbers.
Results
From 1990 to 2021, DM and T2DM incidence in Asia increased, with T2DM showing the most pronounced rise (ASIR increased by 65.03%, EAPC=1.53; T1DM: 27.04%, EAPC=0.80). Substantial heterogeneity was observed across sex, region, and age group. Decomposition analysis indicated that the increase in T2DM cases was primarily driven by epidemiological changes (contributing 99.03%) and population growth (97.84%). Environmental particulate matter pollution, alcohol consumption, and high sugar-sweetened beverage intake were the fastest-rising risk factors, with ASDR increases of 219.61%, 202.01%, and 182.94%, respectively.
Conclusion
Over three decades, Asia’s DM burden has increased, with T2DM as the primary growth source driven by epidemiological changes. Future prevention and control efforts should focus on environmental and behavioral risk factors and implement tiered intervention strategies tailored to population characteristics.

Review Article

Diabetes, obesity and metabolism
Contemporary Type 2 Diabetes Guidelines: Converging Evidence, Diverging Strategies, and the Position of the Korean Diabetes Association Framework: Suk Kyeong Kim, Dong-Lim Kim, Keeho Song, Shinae Kang, Byung-Wan Lee, Jong Han Choi; Endocrinol Metab. 2026;41(3):351-357. Published online June 16, 2026; DOI: https://doi.org/10.3803/EnM.2026.3080

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Abstract PDF PubReader ePub: The pharmacological management of type 2 diabetes mellitus has changed markedly over the past decade, largely in response to evidence generated by cardiovascular and renal outcome trials. Although contemporary guidelines are informed by a broadly shared evidence base, they differ in how they organize treatment concepts and translate evidence into clinical algorithms. This review compares major diabetes guidelines from the American Diabetes Association (ADA), the National Institute for Health and Care Excellence (NICE), the Japan Diabetes Society (JDS), and the Korean Diabetes Association (KDA), with particular attention to pharmacological algorithms, comorbidity-driven treatment strategies, and the conceptual principles underlying each framework. The ADA guideline uses a person-centered, risk-based approach that prioritizes sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists for patients with cardiorenal disease. The NICE guideline applies a more structured strategy, recommending early dual or triple therapy within a cost-effectiveness framework. The JDS guideline emphasizes pathophysiology-based treatment selection tailored to East Asian populations. The KDA guideline retains a glycemia-centered treatment structure while incorporating comorbidity-based decision-making and allowing early, flexible combination therapy. Thus, despite substantial convergence in the evidence base, these guidelines differ in how cardiovascular risk, glycemic control, and pathophysiological heterogeneity are incorporated into treatment decisions. The KDA framework can be viewed as a pragmatic hybrid model that integrates these dimensions and is further extended by recent consensus efforts addressing disease severity and pathophysiology.

Original Articles

Steatotic Liver Disease Subtypes and Advanced Fibrosis as Independent Predictors of Ischemic Stroke in Type 2 Diabetes Mellitus: Myunghwa Jang, Gyuri Kim, Kyu-na Lee, Rosa Oh, So Hyun Cho, Ji Yoon Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Kyungdo Han, Jae Hyeon Kim; Received November 15, 2025 Accepted February 13, 2026 Published online May 18, 2026; DOI: https://doi.org/10.3803/EnM.2025.2792 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Although type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) are associated with an increased risk of ischemic stroke, the extent to which steatotic liver disease (SLD) subtypes and advanced liver fibrosis confer additional risk in individuals with T2DM remains unclear. We aimed to investigate the association of SLD categories and/or advanced liver fibrosis with ischemic stroke risk among patients with T2DM.
Methods
A total of 2,220,249 patients with T2DM were classified into five groups: no steatosis, MASLD, MASLD with other combined disease, metabolic dysfunction and alcohol-related steatotic liver disease (MetALD), and alcohol-related liver disease (ALD) with metabolic dysfunction (MD). SLD was defined using a fatty liver index (FLI) of ≥30, and advanced fibrosis was defined by a BARD score of ≥2.
Results
Over a median follow-up of 11 years, 135,482 ischemic strokes (6.10%) occurred. Compared with no steatosis, adjusted hazard ratios (aHRs) for stroke were higher in MASLD (aHR, 1.10; 95% confidence interval [CI], 1.08 to 1.11), MASLD with combined disease (aHR, 1.14; 95% CI, 1.12 to 1.17), MetALD (aHR, 1.13; 95% CI, 1.11 to 1.16), and ALD with MD (aHR, 1.32; 95% CI, 1.27 to 1.37). Advanced fibrosis progressively increased stroke risk compared with non-SLD and non-fibrotic SLD. Compared with the FLI <30 group, those with FLI 30–60 and ≥60 showed increased aHRs for stroke. Very heavy drinking was associated with a further increase in risk compared with non-drinking.
Conclusion
In patients with T2DM, all SLD categories and advanced liver fibrosis were associated with an increased risk of ischemic stroke. Very heavy alcohol consumption was generally associated with a higher stroke risk across FLI categories.

Hypothalamus and pituitary gland Big Data Articles (National Health Insurance Service Database)
Association between Prolactinoma and Incident Type 2 Diabetes Mellitus: Evidence from a Korean Nationwide Cohort: Han Na Jung, Bo Ram Yang, Min-Seon Kim, Jeong-Hwa Yoon, Se Hee Min; Endocrinol Metab. 2026;41(3):452-460. Published online May 6, 2026; DOI: https://doi.org/10.3803/EnM.2025.2508

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Abstract PDF Supplementary Material PubReader ePub: Background
The effect of prolactinoma on the development of type 2 diabetes mellitus (T2DM) has not been evaluated at the population level. We investigated the association between prolactinoma and incident T2DM in a nationwide cohort.
Methods
We analyzed data from the Korean National Health Insurance Service–National Sample Cohort, which includes 2% of the total national population selected by random sampling, covering the period from 2002 to 2019. A total of 335 patients with newly diagnosed prolactinoma and 1,562 age- and sex-matched controls were included. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for T2DM using Cox proportional hazards regression. Time-dependent HRs were also estimated.
Results
The proportion of prolactinoma patients who developed T2DM was significantly higher than that of controls (10.1% vs. 5.5%; relative risk, 1.84; 95% CI, 1.26 to 2.69). After adjustment for age, sex, income, and comorbidities, the risk of T2DM remained significantly higher in the prolactinoma group (HR, 1.56; 95% CI, 1.01 to 2.41). Subgroup analysis showed a markedly increased risk among individuals aged ≥50 years (HR, 4.47; 95% CI, 1.66 to 12.08). The positive association between prolactinoma and T2DM decreased over time but remained significant for up to 3 years after prolactinoma diagnosis (HR, 9.28 [95% CI, 3.45 to 24.97]; HR, 3.15 [95% CI, 1.55 to 6.38]; and HR, 0.82 [95% CI, 0.44 to 1.53] for ≤1, 1–3, and >3 years, respectively).
Conclusion
Newly diagnosed prolactinoma was independently associated with a higher risk of T2DM, with the association diminishing over 3 years. These findings highlight the importance of monitoring for T2DM during the early management of prolactinoma, particularly in middle-aged patients who may have been previously overlooked.

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Sex Disparity in Suicide Mortality among Patients with Type 2 Diabetes: A Nationwide Population-Based Cohort Study: Chaiho Jeong, Bongseong Kim, Dae Jong Oh, Tae-Seo Sohn, Kyungdo Han, Hyuk-Sang Kwon; Endocrinol Metab. 2026;41(3):405-414. Published online March 19, 2026; DOI: https://doi.org/10.3803/EnM.2025.2669

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Abstract PDF Supplementary Material PubReader ePub: Background
Suicide represents a major public health concern in Korea. Patients with type 2 diabetes mellitus (T2DM) are at higher risk for psychological distress and suicide. Although the male-to-female suicide mortality ratio in the general population has remained about 2.3, the specific differences in suicide mortality by sex among individuals with T2DM are not well characterized.
Methods
We performed a nationwide cohort study utilizing the Korean National Health Insurance Service database, identifying 2,526,769 adults with T2DM who underwent health screening from 2015 to 2016. Participants were monitored until the occurrence of suicide or the study endpoint.
Results
During a median follow-up of 6.0 years, 5,584 suicide deaths occurred (0.30% in men vs. 0.10% in women). Men exhibited a significantly elevated risk of suicide mortality compared to women (adjusted hazard ratio [HR], 2.88; 95% confidence interval [CI], 2.66 to 3.12). The largest disparity was observed in the ≥80 age group (HR, 3.60; 95% CI, 2.88 to 4.51). However, this sex disparity in suicide mortality was reduced among current smokers and heavy alcohol consumers. Among non-smokers, the HR comparing men to women was 3.51 (95% CI, 3.22 to 3.83), while among current smokers, it was 1.73 (95% CI, 1.40 to 2.14). Similarly, the HR among non-drinkers was 3.04 (95% CI, 2.79 to 3.31), compared with 1.36 (95% CI, 0.85 to 2.18) among heavy drinkers.
Conclusion
Men with T2DM had a significantly higher risk of suicide mortality than women, exceeding the sex disparity seen in the general population, with the gap further influenced by age and lifestyle factors.

Songwon Lecture 2025

Diabetes, obesity and metabolism
Postpartum Glucose Intolerance in Women with a History of Gestational Diabetes Mellitus: An In-Depth Review: Kyung-Soo Kim, Soo-Kyung Kim, Yong-Wook Cho; Endocrinol Metab. 2026;41(1):26-33. Published online February 3, 2026; DOI: https://doi.org/10.3803/EnM.2025.2852

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Gestational diabetes mellitus (GDM) is increasing in prevalence worldwide, and postpartum glucose intolerance represents one of the major complications after delivery in women with GDM. A wide range of risk factors for postpartum glucose intolerance have been identified, including ethnicity, genetic predisposition, age, obesity, pre-pregnancy body mass index, gestational weight gain, history of GDM, family history of diabetes, degree of hyperglycemia, insulin treatment, lipid profiles, and other metabolic factors. Lifestyle interventions, including weight loss, are thought to reduce the risk of postpartum glucose intolerance. Careful attention should be paid to the screening of postpartum glucose intolerance in women with GDM, and concerted efforts should be made to prevent or delay the development of diabetes and other metabolic disorders.

Citations

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Diabetes in Pregnancy in Korea: Prevalence, Clinical Characteristics, and Postpartum Comorbidities
Joon Ho Moon, Han Na Jung, Bongseong Kim, Seung-Hyun Ko, Soo Heon Kwak, Kyung-Do Han, Sung Hee Choi
Diabetes & Metabolism Journal.2026; 50(2): 280. CrossRef

Original Articles

Diabetes, obesity and metabolism
Efficacy and Safety of Stage 5 Connected Insulin Pens in Type 1 or Type 2 Diabetes: Randomized Controlled Trial Protocol (SMART-5 Study): 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; Endocrinol Metab. 2026;41(3):393-404. Published online December 12, 2025; DOI: https://doi.org/10.3803/EnM.2025.2579

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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 (Stage 5 connected insulin pen for MDI with Advanced decision support in a Randomized Trial [SMART-5 Study]) 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.

Diabetes, obesity and metabolism
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; Endocrinol Metab. 2026;41(1):162-173. Published online December 3, 2025; DOI: https://doi.org/10.3803/EnM.2025.2479

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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.

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
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; Endocrinol Metab. 2026;41(2):245-255. Published online November 12, 2025; DOI: https://doi.org/10.3803/EnM.2025.2570

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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.

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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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.

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Use of Semaglutide and Tirzepatide in Rheumatic and Musculoskeletal Diseases: Insights on Initiation Patterns and Weight Loss From the Rheumatology Informatics System for Effectiveness Registry
Nicholas P. McCormick, Cristiano S. Moura, Jingyi Zhang, Emily E. Holladay, Fenglong Xie, Tapan Mehta, Joshua F. Baker, Jeffrey R. Curtis
ACR Open Rheumatology.2026;[Epub] CrossRef

Original Articles

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.

Citations

Citations to this article as recorded by

Alcohol and the endocrine system: A critical review of disruptions, potential mechanisms, and health implications
Patricia E. Molina, Liz Simon
Alcohol, Clinical and Experimental Research.2026;[Epub] CrossRef
Impact of Moderate Wine Consumption on Type 2 Diabetes
Attilio Giacosa, Josep Masip, Ursula Fradera, Ramon Estruch, Mariangela Rondanelli
Nutrients.2026; 18(12): 2006. CrossRef
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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Background
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.

Citations

Citations to this article as recorded by

Risk Assessment and Prediction of Hepatocellular Carcinoma in Noncirrhotic Metabolic Dysfunction-Associated Steatotic Liver Disease
Emilie K. Mitten, Piero Portincasa, György Baffy
International Journal of Molecular Sciences.2026; 27(7): 3241. CrossRef
Impact of Fatty Liver Index on Cardiovascular Disease and Mortality across Alcohol Consumption Levels in Young Adults
Byung-Hun Han, Joonyub Lee, Hun-Sung Kim, Jae-Hyoung Cho, Kyungdo Han, Seung-Hwan Lee
Endocrinology and Metabolism.2026;[Epub] CrossRef
Circulating GDF15 levels reflect metabolic and inflammatory burden in early dysglycemia: findings from the ADIOS cohort
Ji Yoon Kim, Ah Hyeon Lee, Jiyoon Lee, Hye-Min Jang, Sin Gon Kim, Dong-Hoon Kim, Nam Hoon Kim
Diabetes Research and Clinical Practice.2026; 239: 113461. CrossRef

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.

Citations

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

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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Progenitor CD8+ T cells and hyper-Treg crosstalk: a driver of immune checkpoint inhibitor resistance in esophageal squamous cell carcinoma
Suning Huang, Jingwei Yan, Wenqi Liu, Baijun Li
Apoptosis.2026;[Epub] CrossRef
Sex differences in animal models of complex disorders: Affective disorders, type 2 diabetes mellitus and essential hypertension
Mai Abu-Moch, Abed N. Azab, Muhammad Yousef, Galila Agam
Biomedicine & Pharmacotherapy.2026; 198: 119356. CrossRef
Biological sex affects human islet gene expression and mitochondrial function in type 2 diabetes
Sing-Young Chen, Haoning Howard Cen, Charlotte F Chao, Andrew R Pepper, James D Johnson, Elizabeth J Rideout
Endocrinology.2026;[Epub] CrossRef
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.2026; 63(2): 214. CrossRef
The Association Between the Triglyceride–Glucose Index and the Risk of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study
Munther S. Momani, Raneem Dalaeen, Dia Sarhan, Zaid Sarhan, Suhib Awamleh, Yazan M. Momani, Omar Abu Farsakh
Life.2026; 16(2): 345. CrossRef
Continuous glucose monitoring and risks of acute and chronic diabetes-related complications and mortality in adults with type 1 diabetes: a nationwide cohort study
Ji Yoon Kim, Seohyun Kim, Jae Hyeon Kim
Diabetologia.2026; 69(7): 1858. CrossRef
Longitudinal trajectories of the triglyceride-glucose index and risk of incident type 2 diabetes in adults undergoing repeated health examinations
Nanping Mao, Ruoli Wang, Yi Wang, Lingna Jin, Yanyun He, Wenbin Wu
Frontiers in Endocrinology.2026;[Epub] CrossRef

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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Costos directos y determinantes de las amputaciones en pacientes diabéticos en un hospital de Nicaragua en el año 2024.
Sidley Irania Hurtado Alvarado, Sheila Karina Valdivia Quiroz
Revista Multidisciplinaria Voces de América y el Caribe.2026; 3(1): 12. CrossRef
Nationwide Big Data Studies of Endocrine Diseases Using the Korean National Health Information Database: Research Trends and Standardization of Operational Definitions
Sun Wook Cho, Jung Hee Kim, Kyoung Jin Kim, Beom-Jun Kim, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2026; 41(1): 86. CrossRef
Cardiovascular outcomes with thiazolidinediones and sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus undergoing peripheral artery revascularization
Ji Woong Roh, Jimin Jeon, Joonsang Yoo, Minyoul Baik, Seok-Jae Heo, Deok-Kyu Cho, Jinkwon Kim
Diabetes Research and Clinical Practice.2026; 236: 113281. CrossRef
Diabetes progression and its association with fracture risk in type 2 diabetes
Bongsung Kim, Kyu-Na Lee, Kyungdo Han, Mee Kyoung Kim
Osteoporosis International.2026;[Epub] CrossRef
Development, validation, and pilot implementation of a prognostic model to predict future foot complications among people with diabetes recently discharged from hospital
Surain B. Roberts, Anne Löffler, Dhanesh Ramachandram, Javier Garay-Fernandez, Maia Norman, Conrad Pow, Fahad Razak, Amol A. Verma, Charles de Mestral
Journal of Clinical Epidemiology.2026; 195: 112295. CrossRef
Hemoglobin-albumin-lymphocyte-platelet score associated with diabetic foot severity, unlike modified systemic immune-inflammatory index and modified systemic inflammatory response index
Weiyu Pan, Zhaoyuan Nie, Qizhi Tang, Ling Zhao
Frontiers in Endocrinology.2026;[Epub] CrossRef
Deep learning-derived retinal biomarker associated with diabetes-related amputation in type 2 diabetes
Junseok Park, Jung Soo Yoon, Sahil Thakur, Dongjin Nam, Sunjin Hwang
Frontiers in Endocrinology.2026;[Epub] CrossRef
Diabetes Progression and Its Impact on Kidney Cancer Risk: Insights From a Longitudinal Korean Cohort Study
Jin Yu, Bongseong Kim, Kyungdo Han, Mee Kyoung Kim
The Journal of Clinical Endocrinology & Metabolism.2025; 111(1): e125. CrossRef
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

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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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.2026; 28(3): 1764. CrossRef
A Pre‐Post Assessment of Blood Glucose Control Following Pharmacist‐Led Professional Continuous Glucose Monitoring in Rhode Island Primary Care Practices
Kelley Doherty Sanzen, Natalya S. Salganik, Susanne M. Campbell, Carolyn A. Karner, Pano M. Yeracaris, Stephen J. Kogut
JACCP: JOURNAL OF THE AMERICAN COLLEGE OF CLINICAL PHARMACY.2026;[Epub] CrossRef
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

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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Kenji Ohwaki, Chino Nakamura, Risa Nasu, Kazumasa Takenouchi, Tetsuaki Hirase
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Yuxian Chen, Haiyong Zeng, Ziqi Luo, Haofei Hu, XinYu Wang
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Hirotaka Watada, Shiro Tanaka, Jessica Y. Matuoka, Hamza Alshannaq, Richard F. Pollock, Martin Field, Gregory J. Norman
Journal of Diabetes Investigation.2026; 17(6): 989. CrossRef
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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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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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Efficacy and safety of adding a fourth oral antidiabetic drug versus metformin dose escalation in patients with type 2 diabetes inadequately controlled on triple oral combination therapy (EFFORT): A 24‐week, randomized, open‐label, multicenter trial
So Ra Kim, Jun Hwa Hong, Sin Gon Kim, Soo‐Kyung Kim, Hyuk‐Sang Kwon, Jun Sung Moon, Jung Hwan Park, Jae Myung Yu, Bong‐Soo Cha, Byung‐Wan Lee
Diabetes, Obesity and Metabolism.2026; 28(4): 3305. CrossRef
Contemporary Type 2 Diabetes Guidelines: Converging Evidence, Diverging Strategies, and the Position of the Korean Diabetes Association Framework
Suk Kyeong Kim, Dong-Lim Kim, Keeho Song, Shinae Kang, Byung-Wan Lee, Jong Han Choi
Endocrinology and Metabolism.2026; 41(3): 351. CrossRef
2025 Clinical Practice Guidelines for Diabetes Management in Korea: Recommendation of the Korean Diabetes Association
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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
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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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Assessing the Impact of Glucagon-like Peptide-1 and Glucagon-like Peptide-1/glucose-dependent Insulinotropic Polypeptide Receptor Agonist Shortages on Glycemic Control: A Single Center Study
Christian Dacon, Pramodini Kale-Pradhan, Melissa Lipari
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Sarah E. Alexander, Erin J. Howden
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European Journal of Clinical and Experimental Medicine.2025;[Epub] CrossRef

Original Article

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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Chan Wu, Hanrong Qin, Maoying Wei, Aijing Li, Qingyi Zhu, Jingyi Guo, Anning Sun, Xin Gu, Yincheng Li, Jun Zhang, Yanbing Gong
Frontiers in Endocrinology.2026;[Epub] CrossRef
Development and validation of a clinical prediction model for overactive bladder in type 2 diabetes: a pathophysiology-informed approach
Meiyuan Lv, Guangxu Fu, Dongfeng Yi, Zhihua Zhang, Liangbing Liu
European Journal of Medical Research.2026;[Epub] CrossRef
Hemoglobin glycation index and renal progression in patients with type 2 diabetes: a 5-year cohort study
Chin-Sung Kuo, Nai-Rong Kuo, Fu-Shun Ko, Po-Hsun Huang, Chii-Min Hwu
Endocrine.2026;[Epub] CrossRef
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Jia Xu, Guangdong Wang, Yongfeng Ni, Zhiyuan Ren
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Qianping Zhang, Yan Zhang, Xuemeng Li, Xinyi Tian, Zhijun Meng, Jin Zhang, Jie Weng, Kaifan Lin, Bihuan Cheng, Yuqiang Gong, Ye Gao
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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
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Weiyi Zhou, Lingyu Zhang, Tongqiang Liu
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Frontiers in Endocrinology.2025;[Epub] CrossRef
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Frontiers in Endocrinology.2025;[Epub] CrossRef
Hemoglobin glycation index predicts reduced mortality in critically ill patients with chronic kidney disease
Yangpei Peng, Wenwen Huang, Jie Wang
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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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Kyung-Soo Kim, Soo-Kyung Kim, Yong-Wook Cho
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Diabetes in Pregnancy in Korea: Prevalence, Clinical Characteristics, and Postpartum Comorbidities
Joon Ho Moon, Han Na Jung, Bongseong Kim, Seung-Hyun Ko, Soo Heon Kwak, Kyung-Do Han, Sung Hee Choi
Diabetes & Metabolism Journal.2026; 50(2): 280. CrossRef
Prevalence, Diagnostic Role, and Clinical Features of Zinc Transporter 8 Autoantibody in Korean Children and Adolescents With Diabetes Mellitus
Sohyun Shin, Hyun Ah Woo, Hakyung Lee, Yun Jeong Lee, Hwa Young Kim, Young Ah Lee, Choong Ho Shin, Ho Young Lee, Jaehyun Kim
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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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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.

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The silent epidemic within the pandemic: pathophysiology and prediction of post-COVID-19 diabetes
Hongjuan Fang, Qiang Wang
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Underweight Status Amplifies Respiratory Infection Mortality in Diabetes: Findings From a Nationwide Cohort Study
Hun Jee Choe, Kyong Do Han, Ji‐Hong Park, Jiwoo Lee, Mi Kyung Kwak, Yun Mi Choi, Sun‐Joon Moon, Eun‐Gyoung Hong
Journal of Cachexia, Sarcopenia and Muscle.2026;[Epub] CrossRef

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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Beyond lipids: fenofibrate in diabetic retinopathy and nephropathy
Mengying Liu, Seok Ting Lim, Weihua Song, Thomas M. Coffman, Xiaomeng Wang
Trends in Pharmacological Sciences.2026; 47(3): 325. CrossRef
Differential Pre‐ and Post‐Treatment Effects of Low‐Dose Antidyslipidemic Drugs on Gentamicin‐Induced Acute Nephrotoxicity in the Rat: A Histopathological and Biochemical Study
Pitchai Balakumar, Sultan Alshahrani, Noohu Abdulla Khan, Rajavel Varatharajan, K. M. Sundram
Journal of Applied Toxicology.2026; 46(6): 1879. CrossRef
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
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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

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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Kyung-Soo Kim, Soo-Kyung Kim, Yong-Wook Cho
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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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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.

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Nephroprotective Potential of Linagliptin and Glimepiride: a Comprehensive Review
Sumaira Tasleem, Farogh Ahsan, Shahzadi Bano, Tarique Mahmood, Asad Ahmad, Soheir A. A. Hagras, Mohammad Sarafroz, Syed Mehdi Hasan Zaidi, Divyanshi Saxena
Current Pharmacology Reports.2026;[Epub] CrossRef

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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Shaminie J. Athinarayanan, Petter Bjornstad, Priya V. Shanmugam, Thomas Weimbs, Adam J. Wolfberg, Jeff S. Volek, Jonathan Himmelfarb, Richard J. Johnson
Diabetes, Obesity and Metabolism.2026;[Epub] CrossRef
Serum ketone body levels and risk of incident kidney and cardiovascular events among patients with type 2 diabetes: a prospective cohort study
Soo Myoung Shin, Jiyoon Lee, Young-Eun Kim, Jung A. Kim, Kyoung Jin Kim, Kyeong Jin Kim, Hee Young Kim, Sin Gon Kim, Nam Hoon Kim
Diabetes Research and Clinical Practice.2026; : 113476. CrossRef
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
Shaminie J. Athinarayanan, Caroline G. P. Roberts, Stephen D. Phinney, Thomas Weimbs, Allon N. Friedman, Jeff S. Volek
Frontiers in Nutrition.2025;[Epub] CrossRef
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
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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.

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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

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.2026; 20(2): 386. CrossRef
Instant messaging-based digital health interventions for diabetes management: a domain-structured systematic review and meta-analysis of randomized controlled trials
Shan Chen, Emma Mirza Wati Mohamad, Arina Anis Azlan, Xixi Zhao
Frontiers in Public Health.2026;[Epub] CrossRef
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
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.

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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
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Yashar Shahbaz, Rasoul Shirmohammadi, Shirin Shamsghahfarokhi, Hooman Esfahani, Mobin Forghan, Hojjat Eghbali Jelodar, Leila Ashrafi, Mohammad Mousavi
Journal of Parathyroid Disease.2025; 13: e13302. 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 Article

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
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Diabetes, Obesity and Metabolism.2026; 28(3): 1764. CrossRef
Development and Validation of a High‐Performance Liquid Chromatography Coupled With Photodiode Array Detection Method for the Simultaneous Analysis of Metformin, Cyanoguanidine, and Antidiabetic Agents in Fixed‐Dose Combinations
Gökhan Bayrak, Selen Al, Aykut Kul, Armağan Önal
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Fikry Ahmad, Suhaili Abubakar, Sharifah Sakinah Syed Alwi, Ng Ooi Chuan, Hasni Idayu Saidi
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A Randomized, Multicenter Study Evaluating the Efficacy, Safety and Tolerability of Dapagliflozin + Gliclazide Fixed Dose Combination Over Dapagliflozin Monotherapy in Type 2 Diabetes Mellitus Patients Inadequately Controlled on Metformin Monotherapy
Suhas G Erande, Amar Raykantiwar, Vivek Shejole, Rashmi GR, Animesh Maiti, A.S. Veeramani Kartheek, Mohamed Hanifah, Richa Giri, Sharvil Gadve, Arindam Ray, Kunal Thakkar, Balram Sharma, Saket Kant, Abhyudaya Verma , Yogesh Yadav, Hiren Prajapati, Honey D
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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.

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Xueqin Xie, Changchun Wu, Ziru Huang, Yuwei Zhou, Jian Huang, Fuying Dao, Dan Yan, Kejun Deng, Hao Lyu, Caiyi Ma, Hao Lin
Briefings in Bioinformatics.2026;[Epub] CrossRef
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Norma Latif Fitriyani, Muhammad Syafrudin, Nur Chamidah, Marisa Rifada, Hendri Susilo, Dursun Aydin, Syifa Latif Qolbiyani, Seung Won Lee
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Jieyun You, Tianwen Wei, Yue Yu, Jing Huang, Yuxiao Sun, Wei Guo, Qi Zhang
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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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Sookyung Won, Hyeon Ji Kim, Jee Yoon Park, Kyung Joon Oh, Sung Hee Choi, Hak Chul Jang, Joon Ho Moon
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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
Endocrinology and Metabolism.2025; 40(5): 668. CrossRef

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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Association between fresh fruit intake and cardiovascular disease risk in patients with diabetes: A prospective cohort study
Xin Fang, Xingyi Zhang, Ze Yang, Yefa Zhang, Shaofeng Huang, Tiehui Chen, Ling Yu, Wenling Zhong
Chinese Medical Journal.2025; 138(2): 243. CrossRef
Nutrition du patient diabétique : banane, pomme de terre… vers une réhabilitation des amylacés
Adrien Rossary, Laurent Miclo
Pratiques en nutrition.2025; 21(81): 29. CrossRef
Estilo de vida e controle glicêmico em pacientes com diabetes mellitus tipo 2: uma revisão integrativa da literatura
Alice Lima Borges, Sueli de Souza Costa, José Braz Costa Castro Junior, Beatriz Lima Soares, Nilson Otávio Sampaio Leite, Francisco Henrique Rodrigues Moraes do Carmo
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Association of low vitamin C concentrations and low consumption of fresh fruit and vegetables with cardiovascular disease in type 2 diabetes
Anna Toffalini, Nicolò Vigolo, Nicoletta Rolli, Elisa Paviati, Matteo Gelati, Elisa Danese, Giacomo Zoppini
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The Relationship between Alcohol Consumption and Diabetes in Korean Adults
Gi Tae Kim, Jae Woong Sull
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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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Indian Journal of Clinical Biochemistry.2026;[Epub] CrossRef
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Minyoung Lee, Min Heui Yu, Wonjeong Chae, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Sung-in Jang, Moon Jae Chung
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Emilia Włoszek, Kamila Krupa, Marta Fudalej, Hanna Miski, Anna M. Badowska-Kozakiewicz, Andrzej Deptała
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Diabetes Duration, Cholesterol Levels, and Risk of Cardiovascular Diseases in Individuals With Type 2 Diabetes
Mee Kyoung Kim, Kyu Na Lee, Kyungdo Han, Seung-Hwan Lee
The Journal of Clinical Endocrinology & Metabolism.2024; 109(12): e2317. CrossRef
Anti-Diabetic Therapies and Cancer: From Bench to Bedside
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Biomolecules.2024; 14(11): 1479. CrossRef

Diabetes, obesity and metabolism
Efficacy of Gemigliptin Add-on to Dapagliflozin and Metformin in Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Study (SOLUTION): Byung Wan Lee, KyungWan Min, Eun-Gyoung Hong, Bon Jeong Ku, Jun Goo Kang, Suk Chon, Won-Young Lee, Mi Kyoung Park, Jae Hyeon Kim, Sang Yong Kim, Keeho Song, Soon Jib Yoo; Endocrinol Metab. 2023;38(3):328-337. Published online June 28, 2023; DOI: https://doi.org/10.3803/EnM.2023.1688

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Background
This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin.
Methods
In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks.
Results
The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted.
Conclusion
Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

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Myung Jin Kim, Yun Kyung Cho, Sehee Kim, Jung Yoon Moon, Chang Hee Jung, Woo Je Lee
Diabetes, Obesity and Metabolism.2025; 27(9): 5019. CrossRef
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Diabetes, Obesity and Metabolism.2025; 27(S9): 3. CrossRef
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Patrizia Natale, Suetonia C Green, David J Tunnicliffe, Giovanni Pellegrino, Tadashi Toyama, Giovanni FM Strippoli
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Diabetes, Obesity and Metabolism.2024; 26(9): 3743. CrossRef

Review Article

Mineral, Bone & Muscle
Skeletal Senescence with Aging and Type 2 Diabetes: Joshua Nicholas Farr; Endocrinol Metab. 2023;38(3):295-301. Published online June 14, 2023; DOI: https://doi.org/10.3803/EnM.2023.1727

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Osteoporosis and type 2 diabetes (T2D) are common diseases that often coexist. While both of these diseases are associated with poor bone quality and increased fracture risk, their pathogenesis of increased fracture risk differs and is multifactorial. Mounting evidence now indicates that key fundamental mechanisms that are central to both aging and energy metabolism exist. Importantly, these mechanisms represent potentially modifiable therapeutic targets for interventions that could prevent or alleviate multiple complications of osteoporosis and T2D, including poor bone quality. One such mechanism that has gained increasing momentum is senescence, which is a cell fate that contributes to multiple chronic diseases. Accumulating evidence has established that numerous boneresident cell types become susceptible to cellular senescence with old age. Recent work also demonstrates that T2D causes the premature accumulation of senescent osteocytes during young adulthood, at least in mice, although it remains to be seen which other bone-resident cell types become senescent with T2D. Given that therapeutically removing senescent cells can alleviate age-related bone loss and T2D-induced metabolic dysfunction, it will be important in future studies to rigorously test whether interventions that eliminate senescent cells can also alleviate skeletal dysfunction in context of T2D, as it does with aging.

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Dissecting Spatiotemporal Heterogeneity of Senescence Markers p16/p21 Across Tissues During Type 2 Diabetes Progression
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Original Articles

Diabetes, obesity and metabolism
Association between Serum Amyloid A Levels and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis: Ting Liu, Meng Li, Chunying Cui, Jielin Zhou; Endocrinol Metab. 2023;38(3):315-327. Published online June 7, 2023; DOI: https://doi.org/10.3803/EnM.2023.1621

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Background
To date, consistent data have not been reported on the association between serum amyloid A (SAA) levels and type 2 diabetes mellitus (T2DM). The purpose of this study was to systematically summarize their relationship.
Methods
Databases including PubMed, Cochrane Library, Embase, Web of Science, and MEDLINE were searched until August 2021. Cross-sectional and case-control studies were included.
Results
Twenty-one studies with 1,780 cases and 2,070 controls were identified. SAA levels were significantly higher in T2DM patients than in healthy groups (standardized mean difference [SMD], 0.68; 95% confidence interval [CI], 0.39 to 0.98). A subgroup analysis showed that the mean age of participants and the continent that participants were from were related to differences in SAA levels between cases and controls. Furthermore, in T2DM patients, SAA levels were positively associated with body mass index (r=0.34; 95% CI, 0.03 to 0.66), triglycerides (r=0.12; 95% CI, 0.01 to 0.24), fasting plasma glucose (r=0.26; 95% CI, 0.07 to 0.45), hemoglobin A1c (r=0.24; 95% CI, 0.16 to 0.33), homeostasis model assessment for insulin resistance (r=0.22; 95% CI, 0.10 to 0.34), C-reactive protein (r=0.77; 95% CI, 0.62 to 0.91), and interleukin-6 (r=0.42; 95% CI, 0.31 to 0.54), but negatively linked with highdensity lipoprotein cholesterol (r=–0.23; 95% CI, –0.44 to –0.03).
Conclusion
The meta-analysis suggests that high SAA levels may be associated with the presence of T2DM, as well as lipid metabolism homeostasis and the inflammatory response.

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Acute peripheral versus central inhibition of insulin receptors differentially alters cytokine and blood–brain barrier responses to an inflammatory stimulus
Tanmai Bandarupalli, Cassidy Noonan, Kim Hansen, Riley Weaver, Kristen Baumann, William A. Banks, Michelle A. Erickson, Elizabeth M. Rhea
Brain, Behavior, and Immunity.2026; 133: 106251. CrossRef
Analysis of Biomarkers in Diabetic Foot Ulcer Patients With Dampness–Heat Syndrome Based on 4D‐DIA Proteomics Technology
Jinlun Jiang, Shiyu Wang, Yiming Ni, Jiawei Feng, Mingmei Zhou, Cheng Zhao, Dana Ciobanu
Journal of Diabetes Research.2026;[Epub] CrossRef
Increased levels of soluble TNF-R1 and serum amyloid A in patients with diabetic nephropathy
Mahboobeh Freidoon, Sara Assadiasl, Hadi Kazemzadehghadim, Naghmeh Sayadi, Narjes Soleimanifar, Sepehr Safdel, Maryam Sadr, Hanieh Mojtahedi, Pedram Chezanisharahi, Mohammad Hossein Nicknam
International Journal of Diabetes in Developing Countries.2026;[Epub] CrossRef
Recent Advances in Studies of Serum Amyloid A: Implications in Inflammation, Immunity and Tumor Metastasis
Yixin Chang, Yezhou Liu, Yuanrui Zou, Richard D. Ye
International Journal of Molecular Sciences.2025; 26(3): 987. CrossRef
From immune activation to disease progression: Unraveling the complex role of Serum Amyloid A proteins
Praveen Papareddy, Heiko Herwald
Cytokine & Growth Factor Reviews.2025; 83: 77. CrossRef
Formyl peptide receptor 2 antagonist WRW4 ameliorates diabetes-induced cognitive decline in mice
Hiroki Uno, Takahide Itokazu, Toshihide Yamashita
Neuroscience Research.2025; 218: 104932. CrossRef
Amyloid Light Chain Proteins in Cardiovascular Disease: Pathogenesis and Emerging Therapies for Cardiac Amyloidosis
Hanyan Hu, Yiqiang Wang, Mingming Xu
Pharmaceutical Research.2025; 42(12): 2405. CrossRef
Serum Amyloid A (SAA) and Its Interaction with High-Density Lipoprotein Cholesterol (HDL-C): A Comprehensive Review
Angela P. Moissl-Blanke, Graciela E. Delgado, Bernhard K. Krämer, Rüdiger Siekmeier, Daniel Duerschmied, Winfried März, Marcus E. Kleber
International Journal of Molecular Sciences.2025; 27(1): 241. CrossRef
Correlation between insulin resistance and the rate of neutrophils-lymphocytes, monocytes-lymphocytes, platelets-lymphocytes in type 2 diabetic patients
Yuanyuan Zhang, Huaizhen Liu
BMC Endocrine Disorders.2024;[Epub] CrossRef
Integrated Network-Based Analysis of Diseases Associated with Amyloid Deposition Through a Disease–Protein–Drug Network
Aikaterini E. I. Rizou, Georgia I. Nasi, Avgi E. Apostolakou, Meletios A. Dimopoulos, Efstathios Kastritis, Vassiliki A. Iconomidou
Pharmaceuticals.2024; 17(12): 1736. CrossRef
Antioxidant and Anti-Inflammatory Functions of High-Density Lipoprotein in Type 1 and Type 2 Diabetes
Damien Denimal
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Diabetes, obesity and metabolism
Effects of Weight Loss and Interaction with Physical Activity on Risks of Cardiovascular Outcomes in Individuals with Type 2 Diabetes: Claudia R. L. Cardoso, Nathalie C. Leite, Gil F. Salles; Endocrinol Metab. 2023;38(3):305-314. Published online May 31, 2023; DOI: https://doi.org/10.3803/EnM.2023.1690

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Background
This study investigated the effects of weight loss during follow-up on cardiovascular outcomes in a type 2 diabetes cohort and tested interactions with clinical and laboratory variables, particularly physical activity, that could impact the associations.
Methods
Relative weight changes were assessed in 651 individuals with type 2 diabetes and categorized as ≥5% loss, <5% loss, or gain. Associations between weight loss categories and incident cardiovascular outcomes (total cardiovascular events [CVEs], major adverse cardiovascular events [MACEs], and cardiovascular mortality) were assessed using multivariable Cox regression with interaction analyses.
Results
During the initial 2 years, 125 individuals (19.2%) lost ≥5% of their weight, 180 (27.6%) lost <5%, and 346 (53.1%) gained weight. Over a median additional follow-up of 9.3 years, 188 patients had CVEs (150 MACEs) and 106 patients died from cardiovascular causes. Patients with ≥5% weight loss had a significantly lower risk of total CVEs (hazard ratio [HR], 0.52; 95% confidence interval, 0.33 to 0.89; P=0.011) than those who gained weight, but non-significant lower risks of MACEs or cardiovascular deaths. Patients with <5% weight loss had risks similar to those with weight gain. There were interactions between weight loss and physical activity. In active individuals, ≥5% weight loss was associated with significantly lower risks for total CVEs (HR, 0.20; P=0.004) and MACEs (HR, 0.21; P=0.010), whereas in sedentary individuals, no cardiovascular protective effect of weight loss was evidenced.
Conclusion
Weight loss ≥5% may be beneficial for cardiovascular disease prevention, particularly when achieved with regular physical activity, even in high-risk individuals with long-standing type 2 diabetes.

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Diabetes, Obesity and Metabolism.2024; 26(2): 567. CrossRef
Body weight variability and the risk of liver‐related outcomes in type 2 diabetes and steatotic liver disease: a cohort study
Nathalie C. Leite, Claudia R. L. Cardoso, Cristiane A. Villela‐Nogueira, Gil F. Salles
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Seung-Hwan Lee
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Effects of body weight variability on risks of macro- and microvascular outcomes in individuals with type 2 diabetes: The Rio de Janeiro type 2 diabetes cohort
Claudia R.L. Cardoso, Nathalie C. Leite, Gil F. Salles
Diabetes Research and Clinical Practice.2023; 205: 110992. CrossRef

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

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

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Namgok Lecture 2022

Diabetes, Obesity and Metabolism
Incretin and Pancreatic β-Cell Function in Patients with Type 2 Diabetes: Chang Ho Ahn, Tae Jung Oh, Se Hee Min, Young Min Cho; Endocrinol Metab. 2023;38(1):1-9. Published online February 13, 2023; DOI: https://doi.org/10.3803/EnM.2023.103

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To maintain normal glucose homeostasis after a meal, it is essential to secrete an adequate amount of insulin from pancreatic β-cells. However, if pancreatic β-cells solely depended on the blood glucose level for insulin secretion, a surge in blood glucose levels would be inevitable after the ingestion of a large amount of carbohydrates. To avoid a deluge of glucose in the bloodstream after a large carbohydrate- rich meal, enteroendocrine cells detect the amount of nutrient absorption from the gut lumen and secrete incretin hormones at scale. Since insulin secretion in response to incretin hormones occurs only in a hyperglycemic milieu, pancreatic β-cells can secrete a “Goldilocks” amount of insulin (i.e., not too much and not too little) to keep the blood glucose level in the normal range. In this regard, pancreatic β-cell sensitivity to glucose and incretin hormones is crucial for maintaining normal glucose homeostasis. In this Namgok lecture 2022, we review the effects of current anti-diabetic medications on pancreatic β-cell sensitivity to glucose and incretin hormones.

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Review Article

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

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

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John R. Ussher, Daniel J. Drucker
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Stephen C Bain, Thinzar Min
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Kwok M. Ho, Anna Lee, William Wu, Matthew T.V. Chan, Lowell Ling, Jeffrey Lipman, Jason Roberts, Edward Litton, Gavin M. Joynt, Martin Wong
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Original Article

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

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

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Brief Report

Diabetes, Obesity and Metabolism
Identification of Healthy and Unhealthy Lifestyles by a Wearable Activity Tracker in Type 2 Diabetes: A Machine Learning-Based Analysis: Kyoung Jin Kim, Jung-Been Lee, Jimi Choi, Ju Yeon Seo, Ji Won Yeom, Chul-Hyun Cho, Jae Hyun Bae, Sin Gon Kim, Heon-Jeong Lee, Nam Hoon Kim; Endocrinol Metab. 2022;37(3):547-551. Published online June 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.1479

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Lifestyle is a critical aspect of diabetes management. We aimed to define a healthy lifestyle using objectively measured parameters obtained from a wearable activity tracker (Fitbit) in patients with type 2 diabetes. This prospective observational study included 24 patients (mean age, 46.8 years) with type 2 diabetes. Expectation–maximization clustering analysis produced two groups: A (n=9) and B (n=15). Group A had a higher daily step count, lower resting heart rate, longer sleep duration, and lower mean time differences in going to sleep and waking up than group B. A Shapley additive explanation summary analysis indicated that sleep-related factors were key elements for clustering. The mean hemoglobin A1c level was 0.3 percentage points lower at the end of follow-up in group A than in group B. Factors related to regular sleep patterns could be possible determinants of lifestyle clustering in patients with type 2 diabetes.

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Review Article

Diabetes, Obesity and Metabolism
Recent Updates to Clinical Practice Guidelines for Diabetes Mellitus: Jin Yu, Seung-Hwan Lee, Mee Kyoung Kim; Endocrinol Metab. 2022;37(1):26-37. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.105

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Guidelines for the management of patients with diabetes have become an important part of clinical practice that improve the quality of care and help establish evidence-based medicine in this field. With rapidly accumulating evidence on various aspects of diabetes care, including landmark clinical trials of treatment agents and newer technologies, timely updates of the guidelines capture the most current state of the field and present a consensus. As a leading academic society, the Korean Diabetes Association publishes practice guidelines biennially and the American Diabetes Association does so annually. In this review, we summarize the key changes suggested in the most recent guidelines. Some of the important updates include treatment algorithms emphasizing comorbid conditions such as atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease in the selection of anti-diabetic agents; wider application of continuous glucose monitoring (CGM), insulin pump technologies and indices derived from CGM such as time in range; more active screening of subjects at high-risk of diabetes; and more detailed individualization in diabetes care. Although there are both similarities and differences among guidelines and some uncertainty remains, these updates provide a good approach for many clinical practitioners who are battling with diabetes.

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Original Article

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Risk and Risk Factors for Postpartum Type 2 Diabetes Mellitus in Women with Gestational Diabetes: A Korean Nationwide Cohort Study: Mi Jin Choi, Jimi Choi, Chae Weon Chung; Endocrinol Metab. 2022;37(1):112-123. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1276

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Background
There are differences in risk and risk factor findings of postpartum type 2 diabetes mellitus (T2DM) after gestational diabetes depending on study design and subjects of previous studies. This study aimed to assess these risk and risk factors more accurately through a population-based study to provide basic data for prevention strategies.
Methods
This open retrospective cohort included data of 419,101 women with gestational diabetes and matched 1,228,802 control women who delivered between 2004 and 2016 from the South Korea National Health Information Database of the National Health Insurance Service. Following 14 (median 5.9) years of follow-up, the incidence and hazard ratio (HR) of postpartum T2DM were evaluated using Kaplan-Meier curves and Cox proportional regression models.
Results
The incidence and HR of postpartum T2DM in women with gestational diabetes (compared to women without gestational diabetes) after the 14-year follow-up was 21.3% and 2.78 (95% confidence interval [CI], 2.74 to 2.82), respectively. Comorbid obesity (body mass index [BMI] ≥25 kg/m²) increased postpartum T2DM risk 7.59 times (95% CI, 7.33 to 7.86). Significant risk factors for postpartum T2DM were fasting glucose level, BMI, age, family history of diabetes, hypertension, and insulin use during pregnancy.
Conclusion
This population-based study showed higher postpartum T2DM risk in women with gestational diabetes than in those without, which was further increased by comorbid obesity. BMI and fasting glucose level were important postpartum risk factors. The management of obesity and glycemic control may be important strategies to prevent the incidence of diabetes after delivery.

Citations

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