Endocrinology and Metabolism最新文献

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.

Backgruound: 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.

Backgruound: 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.

Backgruound: The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design.

Methods: This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models.

Results: During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR, 1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD.

Conclusion: In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

Backgruound: In this comprehensive retrospective nationwide cohort study, we examined the relationships between various asthma medications and bone health, utilizing data from the National Health Insurance Service database of South Korea.

Methods: From 2015 to 2019, the relevant dataset included 168,611 individuals aged 66 years, among whom 8,747 were diagnosed with asthma. We focused on a subset of 6,173 patients, all 66-year-old women. Participants were categorized into four groups: nonusers of asthma medication (n=2,868), leukotriene antagonist users (n=2,281), inhaled corticosteroid (ICS) users (n=517), and those using a combination of ICS and long-acting beta-agonist (ICS+LABA) medication (n=507). The primary outcomes measured were the incidences of major osteoporotic fractures and hip fractures during the follow-up period.

Results: Over 2.7 years of follow-up, 615 cases of major osteoporotic fractures and 96 cases of hip fractures were recorded. ICS users exhibited a heightened risk of both injuries, with hazard ratios of 1.38 (95% confidence interval [CI], 1.18 to 1.63; P<0.001) for major osteoporotic fractures and 1.56 (95% CI, 1.33 to 1.83; P<0.001) for hip fractures. Similarly elevated risks were observed in the ICS+LABA group. Notably, the risk associated with ICS was particularly pronounced among patients with osteopenia for both fracture types. Overall, the use of ICS, alone or in combination with LABA, in patients with asthma is associated with significantly increased risks of osteoporotic fractures, especially among those with osteopenia.

Conclusion: These findings underscore the importance of considering bone health when managing asthma, especially in older patients and those with existing bone density issues.

Backgruound: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia.

Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort.

Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027).

Conclusion: C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Backgruound: 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.

Endogenous Cushing's syndrome (CS) refers to the manifestations of chronic cortisol excess. This rare disease is associated with multiple comorbidities, impaired quality of life, and increased mortality. The management of CS remains challenging. Regardless of the underlying cause, surgical resection of the tumor is typically the first-line and preferred treatment. However, when surgery is not feasible or has been unsuccessful, medical therapies may be employed to control CS. The therapeutic strategy should be individualized based on the recommendations of a multidisciplinary team of experts and the patient's preferences, informed by detailed information on the available options. All medications require careful monitoring, along with adequate instructions for patients and caregivers. The aim of this mini-review is to provide an overview of the main medical therapies currently used to treat CS, including their efficacy, safety, and management. Despite the availability of new drugs in recent years, the need remains for more effective specific targeted pharmacological therapies.

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.