Association between glucagon-like peptide-1 receptor agonists and risk of suicidality: A comprehensive analysis of the global pharmacovigilance database.

AIM: To evaluate the potential association between suicidality and glucagon-like peptide-1 receptor agonists (GLP-1RAs), as well as other medications used for obesity and diabetes, using comprehensive global data. MATERIALS AND METHODS: This study utilized the World Health Organization's pharmacovigilance database, encompassing adverse drug reaction reports from 1967 to 2023, from 170 countries (total reports, N = 131 255 418). We present the reported odds ratios (RORs) with 95% confidence intervals (CIs) and information component (IC) with IC025 regarding the association between GLP-1RA use and suicidality. RESULTS: Although reports of GLP-1RA-associated suicidality increased gradually from 2005 to 2023 (n = 332), no evidence of an association was observed (ROR 0.15 [95% CI 0.13 to 0.16]; IC -2.77 [IC025 -2.95]). The lack of evidence of an association persisted regardless of whether GLP-1RAs were used for diabetes treatment (ROR 0.13 [95% CI 0.11 to 0.14]; IC -2.95 [IC025 -3.14]) or obesity treatment (ROR 0.44 [95% CI 0.34 to 0.58]; IC -1.16 [IC025 -1.62]). However, an association was found between suicidality and other diabetes medications excluding GLP-1RAs (ROR 1.13 [95% CI 1.10 to 1.15]; IC 0.17 [IC025 0.13]). Similarly, the potential association with suicidality was observed in medications used to treat obesity excluding GLP-1RAs (ROR 1.08 [95% CI 1.01 to 1.14]; IC 0.10 [IC025 0.01]). CONCLUSIONS: The suspected association between GLP-1RA use and suicidality, as raised by the European Medicines Agency, was not found in our global analysis. This indicates that the sporadic reports of GLP-1RA-associated suicidality are likely influenced by factors such as comorbidities present in the GLP-1RA user population.

Effect of Hyperprolactinemia on Bone Metabolism: Focusing on Osteopenia/Osteoporosis.

Prolactin is a hormone secreted from lactotroph cells in the anterior pituitary gland to induce lactation after birth. Hyperprolactinemia unrelated to lactation is a common cause of amenorrhea in women of a childbearing age, and a consequent decrease in the gonadotropin-releasing hormone (GnRH) by a high prolactin level can result in decreased bone mineral density. Osteoporosis is a common skeletal disorder characterized by decreased bone mineral density (BMD) and quality, which results in decreased bone strength. In patients with hyperprolactinemia, changes in BMD can be induced indirectly by the inhibition of the GnRH-gonadal axis due to increased prolactin levels or by the direct action of prolactin on osteoblasts and, possibly, osteoclast cells. This review highlights the recent work on bone remodeling and discusses our knowledge of how prolactin modulates these interactions, with a brief literature review on the relationship between prolactin and bone metabolism and suggestions for new possibilities.

Weight Management Health Note, a Mobile Health Platform for Obesity Management Developed by the Korean Society for the Study of Obesity.

The Weight Management Health Note application, developed by the Korean Society for the Study of Obesity (KSSO), was designed to assist individuals in weight management and enhance overall well-being. The Committee of IT-Convergence Treatment of Metabolic Syndrome of the KSSO designed this application. Committee members reviewed and supervised the application's underlying driving algorithms and scientific rationale. A healthcare-specific application developer subsequently finalized the application. This application encompasses a myriad of features, including a comprehensive food diary, an exercise tracker, and tailor-made lifestyle recommendations aligned with individual needs and aspirations. Moreover, it facilitates connections within a community of like-minded individuals endeavoring to manage their weight, fostering mutual support and motivation. Importantly, the application is rich in evidence-based health content curated by the KSSO, ensuring users access accurate information for effective obesity management. Looking ahead, the KSSO is committed to orchestrating diverse academic research endeavors linked to this application and refining its functionalities through continuous feedback from users. The KSSO aspires for this application to serve as a valuable resource for individuals striving to manage their health and enhance their quality of life.

Patterns of hormonal changes in hypophysitis by immune checkpoint inhibitor.

BACKGROUND/AIMS: Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events, including endocrine dysfunctions, which can have serious consequences on patient health and quality of life. The clinical course and characteristics of immune-related hypophysitis (irH) are not well established. This study aimed to analyze the clinical course and characteristics of irH. METHODS: This single-center, retrospective study analyzed data from electronic medical records of Asan Medical Center, spanning January 2017 through June 2021. It included adult patients with solid tumors who underwent thyroid and adrenal function tests, along with gonadotropin and/or growth hormone evaluations, following the initiation of ICI treatment within the same period. The study explored the clinical characteristics of ICI-treated patients with and without irH, the incidence of irH, the time to irH onset, and the associated hormonal changes. RESULTS: Twenty-one patients were included in this analysis. Clinical characteristics did not differ significantly between the irH (n = 13) and non-irH (n = 8) groups. Deficiency rates in the irH group were 23.1% for thyroid-stimulating hormone (n = 3), 76.9% for adrenocorticotropic hormone (n = 10), 61.5% for gonadotropin (n = 8), and 15.4% for growth hormone (n = 2). The overall incidence was 0.9 per person-year, with 6-month and 1-year cumulative incidences of 38.8% and 57.1%, respectively. The median time from ICI initiation to irH diagnosis was 7.7 months. Time to levothyroxine replacement was shorter in the irH group. CONCLUSION: The findings provide evidence that could facilitate the prediction of ICI-induced irH based on clinical course and characteristics.

Prediction model for cardiovascular disease in patients with diabetes using machine learning derived and validated in two independent Korean cohorts.

This study aimed to develop and validate a machine learning (ML) model tailored to the Korean population with type 2 diabetes mellitus (T2DM) to provide a superior method for predicting the development of cardiovascular disease (CVD), a major chronic complication in these patients. We used data from two cohorts, namely the discovery (one hospital; n = 12,809) and validation (two hospitals; n = 2019) cohorts, recruited between 2008 and 2022. The outcome of interest was the presence or absence of CVD at 3 years. We selected various ML-based models with hyperparameter tuning in the discovery cohort and performed area under the receiver operating characteristic curve (AUROC) analysis in the validation cohort. CVD was observed in 1238 (10.2%) patients in the discovery cohort. The random forest (RF) model exhibited the best overall performance among the models, with an AUROC of 0.830 (95% confidence interval [CI] 0.818-0.842) in the discovery dataset and 0.722 (95% CI 0.660-0.783) in the validation dataset. Creatinine and glycated hemoglobin levels were the most influential factors in the RF model. This study introduces a pioneering ML-based model for predicting CVD in Korean patients with T2DM, outperforming existing prediction tools and providing a groundbreaking approach for early personalized preventive medicine.

Impact of metabolic risk factors on hepatic and cardiac outcomes in patients with alcohol- and non-alcohol-related fatty liver disease.

Background & Aims: Metabolic risk factors (MetRs) are associated with hepatic and cardiac outcomes in patients with fatty liver disease (FLD). We evaluated whether MetRs have different effects on alcoholic FLD (AFLD) and non-alcoholic FLD (NAFLD). Methods: We used a standardised common data model to analyse data from seven university hospital databases between 2006 and 2015. MetRs included diabetes mellitus, hypertension, dyslipidaemia, and obesity. Follow-up data were analysed for the incidence of hepatic outcomes, cardiac outcomes, and death in patients with AFLD or NAFLD and based on MetRs within AFLD and NAFLD. Results: Out of 3,069 and 17,067 patients with AFLD and NAFLD, respectively, 2,323 (75.7%) and 13,121 (76.9%) had one or more MetR, respectively. Patients with AFLD were at a higher risk of hepatic outcomes (adjusted risk ratio [aRR], 5.81) compared with those with NAFLD irrespective of MetR. The risk of cardiac outcomes in AFLD and NAFLD became similar with the increasing number of MetRs. Patients with NAFLD without MetRs demonstrated a lower risk of cardiac outcomes, but not hepatic outcomes, compared with those with MetRs (aRR, 0.66 and 0.61 for MetR ≥1 and MetR ≥2, respectively; p <0.05). In patients with AFLD, hepatic and cardiac outcomes were not associated with MetRs. Conclusions: The clinical impact of MetRs in patients with FLD may differ between patients with AFLD and those with NAFLD. Impact and Implications: With the increasing prevalence of fatty liver disease (FLD) and metabolic syndrome, the increase in associated complications, such as liver and heart diseases, has become an important social issue. Particularly in patients with FLD with excessive alcohol consumption, the incidence of liver and heart disease is pronounced because of the dominant effect of alcohol over the effects of other factors. Thus, appropriate screening and management of alcohol consumption in patients with FLD are vital.

Impact of abdominal obesity on the risk of glioma development in patients with diabetes: A nationwide population-based cohort study in Korea.

BACKGROUND: Abdominal obesity has been suggested as a risk factor for glioma; however, it is unclear whether this association applies to people with diabetes. This study examined the association between abdominal obesity and the risk of developing gliomas in diabetic patients. METHODS: We conducted a retrospective cohort study using the National Health Insurance System of South Korea from 2009 to 2012. The primary outcome was the incidence of newly diagnosed gliomas according to waist circumference (WC), and subgroup analyses were performed according to demographic characteristics and diabetes status including disease duration, number of oral hypoglycemic agents, and insulin use. RESULTS: Of a total of 1,893,057 participants, 1,846 (0.10%) cases of gliomas occurred. After adjusting for confounding factors, WC ≥90 cm (men)/85 cm (women) was associated with significantly higher risks of gliomas (adjusted HR [95% CI]; 1.279 [1.053, 1.554], 1.317 [1.048, 1.655], and 1.369 [1.037, 1.807] in the WC <95 cm (men)/90 cm (women) group, WC <100 cm (men)/95 cm (women) group, and WC ≥100 cm (men)/95 cm (women) group, respectively). Subgroup analysis showed that patients with larger WC had a consistently higher incidence of glioma than their lean counterparts, except for insulin users (insulin user vs. nonuser, P for interaction = .03). CONCLUSIONS: Abdominal obesity was associated with the development of gliomas in diabetic patients in a nationwide population-based database. Further study is needed in diabetic patients to stratify the risk for glioma development according to WC and to establish the underlying mechanism of carcinogenesis.

Association between organochlorine pesticides and nonalcoholic fatty liver disease in the National Health and Nutrition Examination Survey 2003-2004.

While endocrine disruptors are emerging as a cause of nonalcoholic fatty liver disease (NAFLD), little is known about the link between NAFLD and organochlorine pesticides (OCPs), one of the endocrine disruptors. We retrospectively analyzed the U.S. National Health and Nutrition Examination Survey 2003-2004 and compared the baseline demographics in individuals according to the presence of NAFLD (fatty liver index [FLI] ≥ 60). Logistic regression analysis was performed to determine whether OCP concentration affected NAFLD prevalence and subgroup analyses regarding NAFLD-related variables and advanced hepatic fibrosis (FIB-4 ≥ 2.67) were performed. Of the 1515 individuals, 579 (38.2%) had NAFLD. Oxychlordane showed concentration-dependent risk for NAFLD (OR 3.471 in fourth quartile [Q4]; 95% CI 1.865-6.458; P = 0.007). p,p'-DDE and trans-nonachlor showed similar trends without statistical significance. Conversely, mirex showed the lowest risk for NAFLD in the highest concentration quartile (OR 0.29 in Q4; 95% CI 0.175-0.483; P < 0.001). Oxychlordane showed the most pronounced association with the levels of each component of FLI and liver enzymes. None of the OCPs were significantly associated with advanced fibrosis. In conclusion, among OCPs, exposure to oxychlordane showed the most prominent impact associated with NAFLD.