Background: Despite diabetes mellitus (DM) and pancreatitis being known risk factors for pancreatic cancer, patients with these conditions are not included in pancreatic cancer screening due to the low incidence of pancreatic cancer in these populations. This study aimed to determine the high-risk subgroup of patients with diabetes and pancreatitis that would benefit from pancreatic cancer screening. Methods: A nested case-control study was conducted using data from the National Health Information Database of the Korean National Health Insurance Service. Patients were categorized into the following groups: type 2 diabetes mellitus only (T2DM-only), pancreatitis-only (PAN-only), T2DM followed by pancreatitis (T2DM-PAN), post-pancreatitis diabetes mellitus (PPDM), and no diabetes and no pancreatitis (NDNP). Conditional logistic regression was used to determine significant associations of each group with pancreatic cancer development risk. Results: The risk of pancreatic cancer was significantly higher in the T2DM-PAN (adjusted odds ratio [AOR], 4.96; 95% confidence interval [CI], 4.48 to 5.49) and PPDM (AOR, 4.71; 95% CI, 4.12 to 5.37) groups than in the NDNP group. Compared to patients in the NDNP group, those with PPDM using insulin had a 17-fold increased risk (AOR, 16.72; 95% CI, 9.50 to 29.43), and individuals with PPDM who had diabetes for less than 3 years had a more than 8-fold increased risk of pancreatic cancer (AOR, 8.83; 95% CI, 5.99 to 13.01). Conclusion In patients with post-pancreatitis diabetes, insulin use or shorter duration of diabetes was associated with a higher risk of pancreatic cancer, suggesting that patients in these subgroups may require close monitoring for pancreatic cancer development.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: This study aimed to examine trends in the prevalence, incidence, metabolic characteristics, and management of type 2 diabetes mellitus (T2DM) among young adults in South Korea. Methods: Young adults with T2DM were defined as individuals aged 19 to 39 years who met the diagnostic criteria for T2DM. Data from the Korean National Health Insurance Service-Customized Database (2010–2020, n=225,497–372,726) were analyzed to evaluate trends in T2DM prevalence, incidence, metabolic profiles, comorbidities, and antidiabetic drug prescription. Additional analyses were performed using the Korea National Health and Nutrition Examination Survey. Results: The prevalence of T2DM in young adults significantly increased from 1.02% in 2010 to 2.02% in 2020 (P<0.001), corresponding to 372,726 patients in 2020. Over the same period, the incidence rate remained stable within the range of 0.36% to 0.45%. Prediabetes prevalence steadily increased from 15.53% to 20.92%, affecting 3.87 million individuals in 2020. The proportion of young adults with T2DM who were obese also increased, with 67.8% having a body mass index (BMI) ≥25 kg/m² and 31.6% having a BMI ≥30 kg/m² in 2020. The prevalence of hypertension, dyslipidemia, and fatty liver disease also increased, reaching 34.2%, 79.8%, and 78.9%, respectively, in 2020. Although the overall pharmacological treatment rate remained low, the prescription of antidiabetic medications with weight-reducing properties increased over the study period. Conclusion The prevalence of T2DM among young adults in South Korea nearly doubled over the past decade. The strong association with obesity and metabolic comorbidities emphasizes the urgent need for targeted prevention and management strategies tailored to this population.

Background: Patients with diabetes are known to be at high risk for end-stage kidney disease (ESKD), but the accurate annual risk data for new-onset ESKD is still limited. In South Korea, the prevalence and incidence of ESKD are increasing more rapidly compared to the global average. This study aimed to determine the incidence rate (IR) of ESKD by diabetes status from 2012 to 2022. Methods: Using data from the Korean National Health Insurance Service, we calculated the IR and hazard ratio (HR) for newonset ESKD in the general population. Individuals were categorized based on diabetes status into nondiabetes, impaired fasting glucose (IFG), diabetes duration <5 and ≥5 years. Results: Among the participants, 67.6% were nondiabetic, 22.3% had IFG, and 10% had diabetes. In Korea, the IRs of ESKD were 139 per million population (pmp) for nondiabetes, 188 pmp for IFG, 632 pmp for diabetes <5 years, and 3,403 pmp for diabetes ≥5 years. An advanced estimated glomerular filtration rate (eGFR) category was the strongest risk factor for ESKD development. However, even in patients with normal renal function, those with long-standing diabetes had a 14-fold higher risk of ESKD compared to nondiabetic individuals. The risk of ESKD associated with diabetes increased exponentially with declining renal function. Notably, IFG showed an increasing tendency for ESKD in younger patients (<65 years) with early-stage chronic kidney disease (CKD; eGFR ≥60 mL/min/1.73 m²). Conclusion Longer diabetes duration amplifies ESKD risk, particularly as renal function declines. Even in patients with normal renal function, long-standing diabetes significantly increases ESKD risk, while IFG is associated with elevated risk only in younger individuals with early-stage CKD.

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.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Background: Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function. Methods: SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test. Results: The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight. Conclusion These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts.

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.