Endocrinology and Metabolism

Original Articles

Sarcopenic Obesity Is Associated with High Insulin Resistance and New-Onset Diabetes Following Pancreaticoduodenectomy: Won-Gun Yun, Youngmin Han, Yoon Soo Chae, Young Jae Cho, Hye-Sol Jung, Wooil Kwon, Jin-Young Jang, Joon Seong Park; Received December 15, 2025 Accepted April 6, 2026 Published online August 6, 2026; DOI: https://doi.org/10.3803/EnM.2025.2859 [Epub ahead of print]

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Abstract PDF: Background
Sarcopenic obesity, characterized by reduced skeletal muscle mass accompanied by excessive visceral fat accumulation, has recently gained attention as a crucial determinant of metabolic dysfunction. Although pancreaticoduodenectomy (PD) is increasingly performed with improved surgical outcomes, the incidence and risk factors for new-onset diabetes after PD remain incompletely understood. This study investigated the impact of sarcopenic obesity on postoperative glucose metabolism.
Methods
A total of 613 patients without preexisting diabetes who underwent PD between 2015 and 2023 were retrospectively analyzed. Diabetes status was evaluated preoperatively and at 3 months postoperatively (Cohort 1), and a subset of 143 patients was reassessed at 1 year (Cohort 2). Sarcopenic obesity was defined as a visceral fat area/skeletal muscle index >2.5 m². Diabetes was defined according to the American Diabetes Association criteria.
Results
At 3 months after surgery, 8.2% (50/613) of patients developed diabetes. Independent predictors included hypertension (odds ratio [OR], 2.45), elevated preoperative hemoglobin A1c (OR, 2.31), and receipt of adjuvant chemotherapy (OR, 3.15). At 1 year, 9.8% (14/143) developed diabetes, with sarcopenic obesity emerging as the sole independent predictor (OR, 3.65; 95% confidence interval, 1.09 to 14.43). Additionally, patients with sarcopenic obesity had significantly higher levels of hemoglobin A1c, Cpeptide, and insulin resistance 1 year after surgery than those without sarcopenic obesity.
Conclusion
Sarcopenic obesity was associated with persistent postoperative insulin resistance. These findings suggest that sarcopenic obesity constitutes a key determinant of new-onset diabetes after PD and highlight the need for preoperative assessment and targeted metabolic interventions in this high-risk population.

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.

YTHDF1-Mediated m⁶A Modification of lncRNA OIP5-AS1 Exacerbates Macrophage Metabolic Dysfunction in Diabetes Mellitus with Coronary Artery Disease: Hongjie Wang, Luyao Li, Zhen Zhen, Zheqi Zhang, Ya Su, Bo Li; Received July 21, 2025 Accepted December 15, 2025 Published online May 7, 2026; DOI: https://doi.org/10.3803/EnM.2025.2566 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Diabetes mellitus (DM) with coronary artery disease (CAD), referred to as DM-CAD, is a prevalent endocrine-metabolic condition characterized by macrophage-driven inflammation and metabolic dysregulation. This study aims to investigate the role of YTH N6-methyladenosine RNA binding protein F1 (YTHDF1)-mediated N⁶-methyladenosine (m⁶A) modification in stabilizing the long non-coding RNA (lncRNA) Opa interacting protein 5 antisense RNA 1 (OIP5-AS1) and to determine its impact on macrophage metabolic dysfunction in DM-CAD.
Methods
Single-cell RNA sequencing and bulk RNA sequencing were performed using DM-CAD mouse models, with downstream analyses conducted using Seurat, CellChat, least absolute shrinkage and selection operator (LASSO) regression, and random forest algorithms. Experimental validation included RNA immunoprecipitation followed by quantitative polymerase chain reaction, actinomycin D-based RNA stability assays, and 2-deoxyglucose (2-DG) interventions in THP-1–derived macrophages, alongside metabolomic profiling and reactive oxygen species (ROS) measurements.
Results
Increased macrophage-endothelial cell coupling was observed in DM-CAD, with both OIP5-AS1 and YTHDF1 significantly upregulated and closely associated with glycolytic metabolic pathways. YTHDF1-mediated m⁶A modification stabilized OIP5-AS1, thereby promoting glycolysis, foam cell formation, ROS production, plaque development, and the upregulation of proinflammatory cytokines, collectively exacerbating atherosclerosis. Notably, treatment with 2-DG markedly reversed these pathological phenotypes.
Conclusion
This study identifies the YTHDF1–m⁶A–OIP5-AS1 axis as a critical regulator of macrophage metabolic dysfunction in DM-CAD, thereby providing an epigenetic framework for understanding disease progression. Targeting this regulatory pathway may attenuate metabolic inflammation and represents a promising therapeutic strategy for endocrine-related cardiovascular complications.

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.

Review Article

Miscellaneous Big Data Articles (National Health Insurance Service Database)
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; Endocrinol Metab. 2026;41(1):86-104. Published online February 26, 2026; DOI: https://doi.org/10.3803/EnM.2026.2953

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Abstract PDF PubReader ePub

The Korean National Health Information Database (NHID) is a large-scale dataset created through linkage of National Health Insurance claims with nationwide health screening records. Because it is released in a cohort-based format, the NHID enables longitudinal follow-up and allows investigation of rare endocrine conditions with low population prevalence. Mortality data, including both dates and causes of death, are additionally obtained through linkage with Statistics Korea. Over recent years, use of the NHID has expanded rapidly, establishing it as a major resource for epidemiological research in endocrinology. Nevertheless, because the database was originally developed for administrative and screening purposes rather than for research, investigators face several methodological limitations, particularly the need to construct and validate robust operational definitions of diseases. In this review, we describe the key features of the Korean NHID, summarize operational definitions of endocrine disorders that have been applied in prior research, and provide an overview of recent endocrine studies conducted using this database.

Citations

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Age-specific loss of life expectancy after hip fracture in Asian adults: A nationwide population-based cohort study
Kyoung Jin Kim, Su Jin Kwon, Seunghyun Lee, Seong Hee Ahn, So Young Park, Ha-Young Kim, Kyoung Min Kim
Bone.2026; 208: 117896. 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

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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Abstract PDF PubReader ePub

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.

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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

Decline in Years of Life Lost Due to Diabetes in Korea, 2008–2019: A Cause-Specific Decomposition Analysis: Da Hea Seo, Kyoung Hwa Ha, Dae Jung Kim; Received August 24, 2025 Accepted November 10, 2025 Published online January 28, 2026; DOI: https://doi.org/10.3803/EnM.2025.2622 [Epub ahead of print]

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Background
This study aimed to evaluate trends in years of life lost (YLL) attributable to diabetes and to identify cause-specific contributors to these changes in Korea.
Methods
We analyzed data from the Korean National Health Insurance Service-National Sample Cohort between 2008 and 2019. Standardized mortality ratios (SMRs) were calculated using indirect standardization with age-specific mortality rates of individuals without diabetes as the reference. YLL was defined as the difference in life expectancy between individuals with and without diabetes at a given age. Cause-specific contributions to changes in YLL were estimated using Arriaga’s decomposition method.
Results
From 2008 to 2019, SMRs declined from 2.19 to 1.55 in males and from 2.04 to 1.36 in females. At age 40, life expectancy among individuals with diabetes increased from 32.53 to 37.81 years in males and from 39.41 to 43.77 years in females, accompanied by a reduction in diabetes-attributable YLL from 8.36 to 5.70 years in males and from 7.51 to 5.21 years in females, representing an approximate 30% decrease. The YLL gap narrowed with increasing age. At age 40, cause-specific decomposition showed that the largest relative reductions in YLL were attributable to diabetes (–40% in males, –46% in females), cardiovascular disease (–37% in males, –52% in females), and kidney disease (–33% in both sexes).
Conclusion
Diabetes-related YLL in Korea declined substantially over the past decade, primarily driven by reductions in mortality from diabetes, cardiovascular disease, and kidney disease.

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Female Gender and Life Expectancy: Systematic Review with ☸️SAIMSARA

SAIMSARA Journal.2026;[Epub] CrossRef

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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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.

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Retrospective Validation of a Stage 5 Decision Support Algorithm Using Clinical Trial Data From Stage 4 Smart Insulin Pens
Jee Hee Yoo, Seohyun Kim, Younghoon Kim, Sang-Man Jin, Jae Hyeon Kim
Journal of Diabetes Science and Technology.2026;[Epub] CrossRef

Diabetes, obesity and metabolism
Impact of Carbohydrate Intake Fluctuations on Glucose Profiles: Insights from Continuous Glucose Monitoring-Based Patient Clustering: Hyun Ah Kim, Kyung Hee Kim, Young Lee, Yoon-Ju Song, Joon Ho Moon, Sung Hee Choi, Tae Jung Oh; Endocrinol Metab. 2026;41(1):152-161. Published online December 12, 2025; DOI: https://doi.org/10.3803/EnM.2025.2486

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

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.

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

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

Brief Report

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

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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
Effects of Progranulin Deficiency on Inflammation and Fibrosis in the Kidneys and Liver of Diabetic Mice Fed a High-Fat Diet: Hiroko Sakuma, Maki Murakoshi, Shinji Hagiwara, Terumi Shibata, Yusuke Suzuki, Tomohito Gohda; Endocrinol Metab. 2026;41(1):138-151. Published online September 30, 2025; DOI: https://doi.org/10.3803/EnM.2025.2339

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

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Effect of Tofogliflozin on Skeletal Muscle Mitochondrial Function in Male Diabetic Mice With Muscle Atrophy
Chiaki Kishida, Maki Murakoshi, Hiroko Sakuma, Terumi Shibata, Yusuke Suzuki, Tomohito Gohda
Journal of the Endocrine Society.2026;[Epub] CrossRef
Progranulin Deficiency Improves Metabolic Stress Yet Falls Short of Sodium-Glucose Cotransporter-2 Inhibition in Autophagy-Linked Renal Protection
Seung-Soon Im
Endocrinology and Metabolism.2026; 41(1): 105. 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
Endocrinology and Metabolism.2025; 40(6): 851. CrossRef

Diabetes, obesity and metabolism
Reduced Sphingosine-1-Phosphate Levels Exacerbate Type 2 Diabetes Mellitus and Associated Complications in a High-Fat Diet Mouse Model: Shih-Chang Hsu, Ching-Lu Chen, Chung Te Liu, Hung-Chieh Lo, Ying-Kuo Liu, Pei-Song Gao, Shau-Ku Huang, Chin-Wang Hsu; Endocrinol Metab. 2026;41(1):108-120. Published online August 5, 2025; DOI: https://doi.org/10.3803/EnM.2025.2360

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

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Early-Onset Dementia Risk Escalates with Diabetes Duration: Insights from a Nationwide Cohort Study: Ji-Hong Park, Sun-Joon Moon, Da Yeon Lee, Ji-Hee Ko, Han Na Jang, Hye-Mi Kwon, Se-Eun Park, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2026;41(2):235-244. Published online July 17, 2025; DOI: https://doi.org/10.3803/EnM.2024.2287

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

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Research Progress on Time in Range as a Predictor of Chronic Complications in Type 2 Diabetes Mellitus
晓雨李
Advances in Clinical Medicine.2026; 16(05): 2100. CrossRef

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

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

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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.

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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.

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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.

Citations

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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

Review Article

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

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

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High incidence of eating disorders in individuals with type 2 diabetes and their association with cardiovascular and mortality risks
So Hyun Cho, Seohyun Kim, Rosa Oh, Ji Yoon Kim, Myunghwa Jang, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim
Diabetologia.2026; 69(3): 653. CrossRef
Epidemiology and characteristics of obesity in Koreans based on the 2024 Obesity Fact Sheet
Eun-Jung Rhee
Journal of the Korean Medical Association.2026; 69(1): 4. CrossRef
Association Between Vitamin D Deficiency and Glycemic, Lipid, and Adiposity Markers in Older Adults: A Nationally Representative Study
Yong-Joon Kim, Kyeongmin Jang
Metabolites.2026; 16(4): 270. CrossRef
Socio-economic Determinants of Health Check-up Attendance among Korean Young Adults: Analysis of the 9th KNHANES (2022-2024)
Chang Soo Lee, Mi Ah Han, Seong Woo Choi, So Yeon Ryu
Journal of Health Informatics and Statistics.2026; 51(2): 83. CrossRef
Dietary advanced glycation end products and risk of cardiometabolic disorders in older adults: cross-sectional data from the 2007–2021 Korea National Health and Nutrition Examination Survey (KNHANES)
Arti Sharma, Jimi Kim
BMC Nutrition.2026;[Epub] CrossRef
Korean Society of Interventional Cardiology Expert Consensus for the Management of Chronic Coronary Syndrome: Part 1
Joo Myung Lee, Yisik Kim, Sang Yoon Lee, Woochan Kwon, Doyeon Hwang, Min Ku Chon, Hyun Sung Joh, Seung Hun Lee, Kwan Yong Lee, Young-Hoon Seo, Seonghyeon Bu, Sang-Don Park, Namkyun Kim, Jung-Sun Kim, Pil-Ki Min, Chang-Wook Nam, Cheol Whan Lee, Young Joon
Journal of Cardiovascular Intervention.2026; 5(3): 173. CrossRef
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Original Article

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

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

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Review Article

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

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

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Original Articles

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

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

Citations

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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
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Kelley Doherty Sanzen, Natalya S. Salganik, Susanne M. Campbell, Carolyn A. Karner, Pano M. Yeracaris, Stephen J. Kogut
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Identification of IL18/IL18R1 signaling as a predictive biomarker of SGLT2 inhibitor efficacy in type 2 diabetes
I-Jou Teng, Chien-Hsing Lee, Ying-Chen Chen, Sheng-Chiang Su, Chieh-Hua Lu, Peng-Fei Li, Chia-Luen Huang, Li-Ju Ho, Ming-Hsun Lin, Hsin-Ya Liu, Feng-Chih Kuo
iScience.2025; 28(10): 113594. CrossRef

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

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

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Diabetes, obesity and metabolism
Prevalence of Mortality and Vascular Complications in Older Patients with Diabetes in Korea: Kwang Joon Kim, Jeongmin Lee, Yang Sun Park, Yong-ho Lee, Kyeong Hye Park, Hee-Won Jung, Chang Oh Kim, Man Young Park, Hun-Sung Kim, Bong-Soo Cha; Endocrinol Metab. 2025;40(3):448-458. Published online February 18, 2025; DOI: https://doi.org/10.3803/EnM.2024.2173

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

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Efficacy and safety of switching to ezetimibe 10 mg/rosuvastatin 2.5 mg in Korean patients with type 2 diabetes mellitus and dyslipidaemia: A multicentre, prospective study (EROICA study)
Sangmo Hong, Won J. Kim, Sungrae Kim, Jung H. Park, Eun S. Kang, Min K. Moon, Jae T. Kim, Ji‐Oh Mok, Ki Y. Lee, Cheol‐Young Park, Chang B. Lee
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Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Time to Insulin Therapy and Severe Hypoglycemia in Korean Adults Initially Diagnosed with Type 2 Diabetes: A Nationwide Study: You-Bin Lee, Kyungdo Han, Bongsung Kim, So Hee Park, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim, Sang-Man Jin; Endocrinol Metab. 2025;40(3):421-433. Published online February 4, 2025; DOI: https://doi.org/10.3803/EnM.2024.2082

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

Songwon Lecture 2024

Diabetes, obesity and metabolism
Gestational Diabetes Mellitus: Mechanisms Underlying Maternal and Fetal Complications: Jooyeop Lee, Na Keum Lee, Joon Ho Moon; Endocrinol Metab. 2025;40(1):10-25. Published online January 23, 2025; DOI: https://doi.org/10.3803/EnM.2024.2264

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Gestational diabetes mellitus (GDM) affects over 10% of all pregnancies, both in Korea and worldwide. GDM not only increases the risk of adverse pregnancy outcomes such as preeclampsia, preterm birth, macrosomia, neonatal hypoglycemia, and shoulder dystocia, but it also significantly increases the risk of developing postpartum type 2 diabetes mellitus and cardiovascular disease in the mother. Additionally, GDM is linked to a higher risk of childhood obesity and diabetes in offspring, as well as neurodevelopmental disorders, including autistic spectrum disorder. This review offers a comprehensive summary of clinical epidemiological studies concerning maternal and fetal complications and explores mechanistic investigations that reveal the underlying pathophysiology.

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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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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
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Diabetes, obesity and metabolism
Metabolic Phenotypes of Women with Gestational Diabetes Mellitus Affect the Risk of Adverse Pregnancy Outcomes: Joon Ho Moon, Sookyung Won, Hojeong Won, Heejun Son, Tae Jung Oh, Soo Heon Kwak, Sung Hee Choi, Hak Chul Jang; Endocrinol Metab. 2025;40(2):247-257. Published online November 28, 2024; DOI: https://doi.org/10.3803/EnM.2024.2089

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Background
Gestational diabetes mellitus (GDM) affects women with diverse pathological phenotypes, but little is known about the effects of this variation on perinatal outcomes. We explored the metabolic phenotypes of GDM and their impact on adverse pregnancy outcomes.
Methods
Women diagnosed with gestational glucose intolerance or GDM were categorized into subgroups according to their prepregnancy body mass index (BMI) and the median values of the gestational Matsuda and Stumvoll indices. Logistic regression analysis was employed to assess the odds of adverse pregnancy outcomes, such as large-for-gestational age (LGA), small-for-gestational age, preterm birth, low Apgar score, and cesarean section.
Results
A total of 309 women were included, with a median age of 31 years and a median BMI of 22.3 kg/m². Women with a higher pre-pregnancy BMI had a higher risk of LGA newborns (adjusted odds ratio [aOR] for pre-pregnancy BMI ≥25 kg/m² compared to 20–23 kg/m², 4.26; 95% confidence interval [CI], 1.99 to 9.12; P<0.001; P for trend=0.001), but the risk of other adverse pregnancy outcomes did not differ according to pre-pregnancy BMI. Women with insulin resistance had a higher risk of LGA (aOR, 1.88; 95% CI, 1.02 to 3.47; P=0.043) and cesarean section (aOR, 2.12; 95% CI, 1.29 to 3.50; P=0.003) than women in the insulin-sensitive group. In contrast, defective β-cell function did not affect adverse pregnancy outcomes.
Conclusion
Different metabolic phenotypes of GDM were associated with heterogeneous pregnancy outcomes. Women with obesity and those with insulin resistance are at greater risk of adverse outcomes and might need strict glycemic management during pregnancy.

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Long-term risk of offspring type 1 and type 2 diabetes following maternal gestational diabetes mellitus: a nationwide birth cohort study with 10-year follow-up
Joon Ho Moon, Han Na Jung, Bongseong Kim, Jaehyun Kim, Young Mi Jung, Hyeon Ji Kim, Jee Yoon Park, Tae Jung Oh, Soo Heon Kwak, Kyung-Do Han, Sung Hee Choi
BMC Medicine.2026;[Epub] CrossRef
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BMC Pregnancy and Childbirth.2026;[Epub] CrossRef
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Endocrinology and Metabolism.2026; 41(1): 26. CrossRef
Placental transport dysfunction in omega-3 and omega-6 fatty acid in patients with gestational diabetes mellitus
Wei Long, Fang Guo, Jun Yao, Qinjun Wei, Lizhong Yin, Jiawen Xu, Xin Cao
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Machine learning‐based prediction model for adverse pregnancy outcomes in women with gestational diabetes mellitus
Jooyeop Lee, Seoung‐Ho Choi, Hyeon Ji Kim, Jee Yoon Park, Tae Jung Oh, Sung Hee Choi, Hak Chul Jang, Joon Ho Moon
Journal of Diabetes Investigation.2026;[Epub] CrossRef
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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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Original Articles

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

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

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

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

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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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Kyuho Kim, Bongseong Kim, Kyuna Lee, Yu-Bae Ahn, Seung-Hyun Ko, Sung Hee Choi, Kyungdo Han, Jae-Seung Yun
Diabetes & Metabolism Journal.2025; 49(2): 183. CrossRef
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Rosa Oh, Seohyun Kim, Sang Ho Park, Myunghwa Jang, So Hyun Cho, Ji Yoon Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim
Cardiovascular Diabetology.2025;[Epub] CrossRef
Association Between Healthy Dietary Patterns and Chronic Kidney Disease in Patients with Diabetes: Findings from Korean National Health and Nutrition Examination Survey 2019–2021
Minsang Kim, Jung Koh, Jeong Cho, Semin Cho, Soojin Lee, Hyuk Huh, Seong Kim, Sehyun Jung, Eunjeong Kang, Sehoon Park, Jin Paek, Woo Park, Kyubok Jin, Seungyeup Han, Kwon Joo, Kyungdo Han, Dong Kim, Yaerim Kim
Nutrients.2025; 17(9): 1600. CrossRef
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Kyoung Hwa Ha, Dae Jung Kim
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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
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Ju-young Lee, Youngeun Yoo, Sanghun Lee
Acupuncture & Electro-Therapeutics Research: International Journal of Integrated Medicine.2025; 49(4): 230. CrossRef
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Shiva Raj Acharya, Sudarshan Subedi, Diwash Timilsina
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Original Articles

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

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

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Undescribed phenylspirodrimane dimers with anti-gouty activity from the coral-derived fungus Stachybotrys chartarum
Shuang Lin, Yi-Fan Geng, Hanxiao Zeng, Zixue Chai, Baolei Fan, Jun-Cheng Su, Yonghui Zhang, Zhengxi Hu
Phytochemistry.2026; 248: 114891. CrossRef
Gout in the era of multimorbidity: pathogenesis, systemic comorbidities, and evolving therapeutic strategies
Phillip J Kim, Jihun Kang, Jesang Yu, Geun-Tae Kim, Yunkyung Kim
Kosin Medical Journal.2026; 41(1): 26. CrossRef
Acute gout attack in a peritoneal dialysis patient treated with Firsekibart: a case report
Wenqian Wei, Lijie Gu, Hanyu Meng, Nan Zhu, Shu Rong
Open Medicine.2026;[Epub] CrossRef
Polydatin alleviates adenine-induced nephropathy in mice
Tao Sheng, Tianhong Ma, Xin Jin, Debin Chen, Shipeng Che, Jie Wang, Jiadu Shen, Chaoqun Shi, Qiang Li, Yixin Sun, Deqing Chen, Guangtao Xu
Renal Failure.2026;[Epub] CrossRef
Association between TyHGB and hyperuricemia and gout in patients with type-2 diabetes mellitus
Qian Zhang, Jing Xu, Yanying Qian
BMC Endocrine Disorders.2026;[Epub] CrossRef
Heterogeneity in the development of diabetes-related complications: narrative review of the roles of ancestry and geographical determinants
Andrea O. Y. Luk, Yingnan Fan, Baoqi Fan, Edith W. K. Chow, Tony C. K. O
Diabetologia.2025; 68(11): 2386. CrossRef
Relationship between the Chinese visceral adiposity index and gout in individuals with type 2 diabetes mellitus: a cross-sectional population-based study
Ningyu Cai, Mengdie Chen, Ping Feng, Yiyun Wang, Xianping Zhu, Qidong Zheng
Frontiers in Nutrition.2025;[Epub] CrossRef

Diabetes, obesity and metabolism
Insulin Resistance and Impaired Insulin Secretion Predict Incident Diabetes: A Statistical Matching Application to the Two Korean Nationwide, Population-Representative Cohorts: Hyemin Jo, Soyeon Ahn, Jung Hun Ohn, Cheol Min Shin, Eunjeong Ji, Donggil Kim, Sung Jae Jung, Joongyub Lee; Endocrinol Metab. 2024;39(5):711-721. Published online August 30, 2024; DOI: https://doi.org/10.3803/EnM.2024.1986

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Background
To evaluate whether insulin resistance and impaired insulin secretion are useful predictors of incident diabetes in Koreans using nationwide population-representative data to enhance data privacy.
Methods
This study analyzed the data of individuals without diabetes aged >40 years from the Korea National Health and Nutrition Examination Survey (KNHANES) 2007–2010 and 2015 and the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Owing to privacy concerns, these databases cannot be linked using direct identifiers. Therefore, we generated 10 synthetic datasets, followed by statistical matching with the NHIS-HEALS. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were used as indicators of insulin resistance and insulin secretory function, respectively, and diabetes onset was captured in NHIS-HEALS.
Results
A median of 4,580 (range, 4,463 to 4,761) adults were included in the analyses after statistical matching of 10 synthetic KNHANES and NHIS-HEALS datasets. During a mean follow-up duration of 5.8 years, a median of 4.7% (range, 4.3% to 5.0%) of the participants developed diabetes. Compared to the reference low–HOMA-IR/high–HOMA-β group, the high–HOMA-IR/low– HOMA-β group had the highest risk of diabetes, followed by high–HOMA-IR/high–HOMA-β group and low–HOMA-IR/low– HOMA-β group (median adjusted hazard ratio [ranges]: 3.36 [1.86 to 6.05], 1.81 [1.01 to 3.22], and 1.68 [0.93 to 3.04], respectively).
Conclusion
Insulin resistance and impaired insulin secretion are robust predictors of diabetes in the Korean population. A retrospective cohort constructed by combining cross-sectional synthetic and longitudinal claims-based cohort data through statistical matching may be a reliable resource for studying the natural history of diabetes.

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Association between body weight time in target range and risk of type 2 diabetes in adults with obesity
Soojin Park, Seohyun Kim, Sang Ho Park, Minkyeong Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim, Gyuri Kim
Diabetology & Metabolic Syndrome.2026;[Epub] CrossRef
Abnormal insulin metabolism and decreased levels of mindfulness in type 2 diabetes mellitus
Xue Zhang, Rui Huang, Jiaxin Li, Mingyue Yang, Daowen Zhang, Cancan Liu, Kuanlu Fan
Diabetology & Metabolic Syndrome.2025;[Epub] CrossRef
Association of Insulin Resistance with Dysglycemia in Elder Koreans: Age- and Sex-Specific Cutoff Values
Sang Min Yoon, Boyoung Park
Journal of Personalized Medicine.2025; 15(9): 438. CrossRef
Evaluating the utility of data integration with synthetic data and statistical matching
Eunjeong Ji, Jung Hun Ohn, Hyemin Jo, Min-Jeong Park, Hang J. Kim, Cheol Min Shin, Soyeon Ahn
Scientific Reports.2025;[Epub] CrossRef
Neck to Waist Circumference Ratio and Insulin Resistance in Adult Korean Population Under 50 Years
Kyu Rae Lee
Metabolic Syndrome and Related Disorders.2025; 23(9): 422. CrossRef
Combining Nationwide Cohorts to Unveil the Predictive Role of Insulin Resistance and Impaired Insulin Secretion in Diabetes
Bukyung Kim
Endocrinology and Metabolism.2024; 39(5): 699. CrossRef

Brief Report

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

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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
Journal of Translational Medicine.2026;[Epub] CrossRef
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
Development and Validation of Green UV Spectrophotometric Method Using Augmented Classical Least Squares for Simultaneous Quantification of Atorvastatin, Ezetimibe, and Fenofibrate in Pharmaceutical and Environmental Samples
Ahmed M. Abdelzaher, Omkulthom Al kamaly, Anwar M. Alnakhli, Mona A. Abdel Rahman
ChemistrySelect.2026;[Epub] CrossRef
Current and Emerging Treatment Options for Hypertriglyceridemia: State-of-the-Art Review
Jakub Michal Zimodro, Manfredi Rizzo, Ioanna Gouni-Berthold
Pharmaceuticals.2025; 18(2): 147. CrossRef
Fenofibrate therapy and risk of heart failure outcomes in patients with Type 2 diabetes: a propensity-matched cohort study
Ji Yoon Kim, Nam Hoon Kim, Jiyoon Lee, Dong-Hoon Kim, Sin Gon Kim
European Heart Journal - Cardiovascular Pharmacotherapy.2025; 11(7): 620. CrossRef

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.

Citations

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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
Endocrinology and Metabolism.2026; 41(1): 26. CrossRef
FGF21 and SHBG as Putative Hepatic Axes in Maternal Metabolic Adaptation: A Hypothetical Framework for Postpartum Insulin Sensitivity Restoration
Kornelia Purc-Bandurko, Katarzyna Trojnar, Angelika Masiarz, Adrian Bandurko, Żaneta Kimber-Trojnar, Bożena Leszczyńska-Gorzelak
Biomolecules.2026; 16(7): 998. CrossRef
Machine learning‐based prediction model for adverse pregnancy outcomes in women with gestational diabetes mellitus
Jooyeop Lee, Seoung‐Ho Choi, Hyeon Ji Kim, Jee Yoon Park, Tae Jung Oh, Sung Hee Choi, Hak Chul Jang, Joon Ho Moon
Journal of Diabetes Investigation.2026;[Epub] CrossRef
Gestational Diabetes Mellitus: Mechanisms Underlying Maternal and Fetal Complications
Jooyeop Lee, Na Keum Lee, Joon Ho Moon
Endocrinology and Metabolism.2025; 40(1): 10. CrossRef
Evaluation of Maternal Factors Affecting Postpartum Insulin Resistance Markers in Mothers with Gestational Diabetes—A Case–Control Study
Karolina Karcz, Paulina Gaweł, Barbara Królak-Olejnik
Nutrients.2024; 16(22): 3871. CrossRef

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

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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

Review Article

Diabetes, obesity and metabolism
Artificial Intelligence Applications in Diabetic Retinopathy: What We Have Now and What to Expect in the Future: Mingui Kong, Su Jeong Song; Endocrinol Metab. 2024;39(3):416-424. Published online June 10, 2024; DOI: https://doi.org/10.3803/EnM.2023.1913

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Diabetic retinopathy (DR) is a major complication of diabetes mellitus and is a leading cause of vision loss globally. A prompt and accurate diagnosis is crucial for ensuring favorable visual outcomes, highlighting the need for increased access to medical care. The recent remarkable advancements in artificial intelligence (AI) have raised high expectations for its role in disease diagnosis and prognosis prediction across various medical fields. In addition to achieving high precision comparable to that of ophthalmologists, AI-based diagnosis of DR has the potential to improve medical accessibility, especially through telemedicine. In this review paper, we aim to examine the current role of AI in the diagnosis of DR and explore future directions.

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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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Abstract PDF Supplementary Material PubReader ePub

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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Effectiveness of Telehealth Low‐Carbohydrate Intervention in Preventing Chronic Kidney Disease: A Real‐World, Retrospective, Matched Cohort Study
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
Endocrinology and Metabolism.2025; 40(6): 851. CrossRef
Trigger Warning: How Modern Diet, Lifestyle, and Environment Pull the Trigger on Autosomal Dominant Polycystic Kidney Disease Progression
Melina Messing, Jacob A. Torres, Nickolas Holznecht, Thomas Weimbs
Nutrients.2024; 16(19): 3281. CrossRef

Original Article

Diabetes, obesity and metabolism
Reference Standards for C-Peptide in Korean Population: A Korean Endocrine Hormone Reference Standard Data Center Study: Jooyoung Cho, Ho-Chan Cho, Ohk-Hyun Ryu, Hyo-Jeong Kim, Chang Geun Kim, Young Ran Yun, Choon Hee Chung, on Behalf of the Task Force Team for Korean Hormone Reference Standards; Endocrinol Metab. 2024;39(3):489-499. Published online May 9, 2024; DOI: https://doi.org/10.3803/EnM.2023.1888

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Background
The Korean Endocrine Hormone Reference Standard Data Center (KEHRS DC) has created reference standards (RSs) for endocrine hormones since 2020. This study is the first of its kind, wherein the KEHRS DC established RSs for serum Cpeptide levels in a healthy Korean population.
Methods
Healthy Korean adults were recruited from May 2021 to September 2023. After excluding participants according to our criteria, serum samples were collected; each participant could then choose between fasting glucose only or fasting glucose plus an oral glucose tolerance test (OGTT). If their sample showed high glucose (≥100 mg/dL) or hemoglobin A1c (HbA1c) (≥5.70%), their C-peptide levels were excluded from analyzing the RSs.
Results
A total of 1,532 participants were recruited; however, only the data of 1,050 participants were analyzed after excluding those whose samples showed hyperglycemia or high HbA1c. Post-30-minute OGTT data from 342 subjects and post-120-minute OGTT data from 351 subjects were used. The means±2 standard deviations and expanded uncertainties of fasting, post-30-minute and 120-minute OGTT C-peptide levels were 1.26±0.82 and 0.34–3.18, 4.74±3.57 and 1.14–8.33, and 4.85±3.58 and 1.25–8.34 ng/mL, respectively. Serum C-peptide levels correlated with obesity, serum glucose levels, and HbA1c levels.
Conclusion
The RSs for serum C-peptide levels established in this study are expected to be useful in both clinical and related fields.

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Call for Standardization of C-Peptide Measurement
Erwin Schleicher, Kuanysh Kabytaev, Matthias Nauck, Dirk Müller-Wieland, Andreas Peter, Randie R. Little, Lutz Heinemann
Journal of Diabetes Science and Technology.2025;[Epub] CrossRef

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