Application of lacrimal gland herniation in judging the activity of thyroid-associated ophthalmopathy and predicting the efficacy of glucocorticoids

Objective To evaluate the value of lacrimal gland herniation（LGH）in judging the activity of thyroid-associated ophthalmopathy（TAO）and predicting the efficacy of glucocorticoids. Methods A retrospective analysis was conducted on the clinical data of 238 patients with TAO who were hospitalized at the Department of Endocrinology and Metabolic Diseases，the Third Affiliated Hospital of Sun Yat-sen University，from January 2014 to November 2022. Magnetic resonance imaging（MRI）was used to measure LGH and its differences were compared among different activity groups. Spearman rank correlation analysis was used to assess the correlation between LGH and the clinical activity score（CAS）. The effectiveness of LGH in staging TAO activity was evaluated using the receiver operating characteristic（ROC）curve. Follow-up was performed on 92 patients receiving glucocorticoid therapy to analyze the differences in LGH between the different efficacy groups. The influencing factors of efficacy were analyzed by multivariate Logistic regression analysis. Results The LGH of patients in the active group was higher than that in the non-active group（P < 0.05）. Spearman rank correlation analysis results showed a positive correlation between LGH and CAS score（P < 0.05）. The ROC curve analysis showed that the staging efficacy of LGH for TAO activity was optimal when the cut-off value of LGH was 9.78 mm，with an area under the curve（AUC）of 0.703，sensitivity of 78.9%，and specificity of 54.8%. Combining external ocular muscle thickness（EOMT）with LGH further improved staging efficacy，with an AUC of 0.752，sensitivity of 62.7%，and specificity of 78.1%. The AUC for the combined EOMT and LGH was greater than that for LGH alone（Z = 2.052，P < 0.05）. In the glucocorticoid treatment efficacy group，LGH was lower than in the ineffective group（P < 0.05）. Multivariate Logistic regression analysis indicated that LGH was an independent predictor of efficacy（P < 0.05）. Conclusions The LGH of TAO patients is correlated with the CAS score and can be used as a good indicator to judge the activity of TAO. The combination of LGH and EOMT can effectively improve the staging efficacy of TAO，thus providing effective assistance for precise clinical diagnosis and treatment

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

1885-P: Caveolin1 Attenuates Palmitic Acid-Induced Hepatic Steatosis through Upregulating PGC1α-sirt3 Axis

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Caveolae are flask-shaped invaginations of the plasma membrane enriched with cholesterol and phospholipid. Caveolin1 is the resident structural protein of caveolae and has previously been reported to involve in hepatic steatosis and NAFLD, while the mechanism remains elusive. Here we examined the effects of caveolin1 on palmitic acid (PA)-induced hepatic steatosis. Stable caveolin1 overexpressing HepG2 cells were developed by transfection with lentiviral particles containing human CAV1 protein (Lenti-CAV1). Lenti-Control served as a negative control. Compared with BSA treatment, PA treatment of HepG2 cells for 24 hours increased the lipid droplets and TG level (P&amp;lt;0.01). Compared with negative control, overexpression of caveolin1 attenuated the accumulation of lipid droplets and triglyceride content in HepG2 cells (P&amp;lt;0.05). At the same time, quantitative real-time PCR revealed that the mRNA expression of PGC1α and sirt3 were increased in caveolin1 overexpressing cells (P&amp;lt;0.05). In conclusion, caveolin1 may improve PA-induced hepatic steatosis through up-regulating PGC1α-sirt3 axis. Disclosure C. Lin: None. W. Zeng: None. S. Lin: None. K. Liu: None. L. Zeng: None. </jats:sec

1351-P: Association of Muscle/Fat Mass Ratio in the First Trimester with Gestational Diabetes Mellitus in Chinese Subjects

This study aims to evaluate the association of muscle/fat mass ratio in the first trimester with gestational diabetes mellitus (GDM) in Chinese subjects. A total of 3011 pregnant women were recruited from our hospital, Guangzhou, China, from Jan 2017 to Dec 2017. The muscle/fat mass ratio (&amp;lt; 13+6 weeks’ gestation) and 75-g OGTT (24-28 weeks’ gestation) were measured in each subject. The muscle/fat mass ratio was assessed by bioelectrical impedance analysis. GDM was diagnosed according the IADPSG guideline (2010). All subjects had average age 29 years (interquartile range:27-32 years), mean pregestational body mass index 20.7±2.6kg/m2, muscle/fat mass ratio 2.64±0.65. Five hundred and forty eight subjects (17.9%) were diagnosed as GDM. The prevalence of GDM were 25.9%, 20.4%, 14.1%, and 11.3% among subjects with muscle/fat mass ratio in 1st quartile (≤2.15), 2nd quartile (2.16-2.61), 3rd quartile (2.62-3.08), and 4th quartile(≥3.09), respectively. The prevalence of GDM decreased while muscle/fat mass ratio increased. The area under ROC curve was 0.612 (0.595-0.630) for the muscle/fat mass ratio in predicting GDM (P&amp;lt;0.0001) and the threshold of 2.59 yielded the highest combination of sensitivity (63.2%) and specificity (55.7%). This study suggested the muscle/fat mass ratio in the first trimester may be used as an index to predict GDM in Chinese subjects. Disclosure P. Li: None. S. Lin: None. J. Fan: None. L. Zeng: None. Funding Science and Technology Planning Project of Guangdong Province (2017A020215026); Medical Scientific Research Foundation of Guangdong Province (A2017314) </jats:sec

Tariff-Based Optimal Scheduling Strategy of Photovoltaic-Storage for Industrial and Commercial Customers

Photovoltaic (PV) power generation exhibits stochastic and uncertain characteristics. In order to improve the economy and reliability of a photovoltaic-energy storage system (PV-ESS), it is crucial to optimize both the energy storage capacity size and the charging and discharging strategies of the ESS. An optimal scheduling model for PV-ESS is proposed in this paper, comprehensively considering factors in terms of energy cost and charging/discharging constraints of the PV-ESS. Moreover, the model employs a particle swarm optimization-backpropagation (PSO-BP) neural network to predict the PV power using historical generation data from a factory in Xiamen. The proposed two PV-ESS scheduling strategies are compared under three weather conditions. In the demand management strategy, the ESS can flexibly respond to different weather conditions and load demand changes, and effectively reduce the electricity cost for users

2091-P: Effects of Caveolin-1 on the Synthesis and Decomposition of Islet ß-Cell IAPP and Its Mechanism

Objective: Islet amyloid polypeptide(IAPP) is a major component of islet amyloid deposition in type 2 diabetic patients. Our preliminary study showed that membrane protein Caveolin-1 (Cav1) silencing inhibited β-cell apoptosis and promote insulin secretion. The purpose of this study was to investigate the regulation of Cav1 on islet β-cell IAPP and its mechanism. Materials and Methods: Firstly, IAPP secretion of each group of primary islets was detected by ELISA, then Western blot and real-time quantitative PCR (qPCR) were used to detect the expression levels of IAPP, PAM(Peptidyl-glycine alpha-amidating monooxygenase), PC1(Prohormone Convertase-1), BACE2(Beta-secretase 2), IDE(Insulin-Degrading Enzyme), TXNIP(Thioredoxin interacting protein), and finally, it confirmed that Cav1 interacted with the protein of TXNIP by immunofluorescence confocal and co-immunoprecipitation (Co-IP). Results: The secretion of IAPP was decreased in primary pancreatic islets and Cav1 deficiency significantly down-regulated the expression of IAPP in NIT-1 cells, while over-expression of Cav1 in βTC-6 cells significantly up-regulated the expression of IAPP. This effect correlated with Cav1 silencing leading to down-regulation of PAM expression associated with IAPP synthesis and over-expression of Cav1 leading to up-regulation of PC1 associated with IAPP synthesis. On the other hand,Cav1 deficiency resulted in the up-regulation of the expression of BACE2 and IDE, the enzymes associated with IAPP decomposition. While over-expression of Cav1 leaded to down-regulation of BACE2 and IDE. Further studies indicated that Cav1 co-localized with TXNIP, and it interacted with and regulated the expression of TXNIP, which regulates IAPP gene transcription. Conclusion: Cav-1 can regulate the synthesis and decomposition of IAPP in islet β cell by interacting with TXNIP. This study suggests that Cav-1 may protect diabetic islet beta cells by reducing islet amyloid deposition. Disclosure K. Liu: None. W. Zeng: None. S. Lin: None. C. Lin: None. F. Xu: None. N. Cai: None. L. Zeng: None. Funding National Natural Science Funding of China (51873071); Natural Science Foundation of Guangdong Province (2018B030311012) </jats:sec

1062-P: Insulin Requirement Profiles of Short-Term Continuous Subcutaneous Insulin Infusion Therapy in Chinese Patients with Type 2 Diabetic Nephropathy

Our study aims to explore the insulin requirement profiles of short-term intensive continuous subcutaneous insulin infusion (CSII) in Chinese patients with type 2 diabetic nephropathy. CSII was applied in 68 patients with diagnosed type 2 diabetic nephropathy (using Paradigm 712, Medtronic). Daily insulin doses were titrated and recorded to achieve and maintain target glucose levels (FPG&amp;lt;7.0mmol/L and 2hPBG&amp;lt;10mmol/L) for 8-12 days. The patients were 60.0±13.1 years in age, 45.6% female (n=31), mean duration 11.3±7.2 years, BMI 25.0±3.3 kg/m2, mean HbA1c of 9.4±2.5%, median urinary microalbumin/creatine 78.2 mg/g (inter-quartile range 36.0-274.6 mg/g), and median creatine 72.0umol/l (inter-quartile range 53.5-110.8 umol/l). At the first day after the glycemic targets were achieved (Day1), total daily insulin dose (TDD), total basal and premeal dose were 44.3±17.5 IU (0.67±0.27 IU/kg), 19.6±9.2 IU (0.30±0.14 IU/kg) and 24.7±10.3 IU (0.37±0.15 IU/kg), respectively. At the end of CSII therapy, TDD was 43.7±18.1 IU (0.66±0.28 IU/kg). Total basal dose and total pre-meal dose were 19.2±9.0 IU (0.29±0.14 IU/kg, P&amp;gt;0.05 compared with Day1) and 24.5±11.2 (0.37±0.17 IU/kg, P &amp;gt; 0.05 compared with Day1), respectively. The ratio of basal insulin dose to TDD were 44%±11% at Day1 and 44%±12% at the end, respectively. The ratio of basal insulin dose to TDD at day 1 were 45%±11% and 40%±9% in subjects with eGFR &amp;gt;60ml/min (n=48) or eGFR &amp;lt;60ml/min (n=20), respectively (P=0.11). The ratio of basal insulin dose to TDD at day 1 were 49%±18% and 39%±12% in subjects with eGFR 60-90 ml/min or eGFR &amp;lt;30ml/min, respectively (P=0.041). The TDD at Day1 were 45.8±12.4 IU in subjects with 40.9±26.1 IU in subjects with eGFR &amp;gt;60ml/min or eGFR &amp;lt;60ml/min, respectively (P&amp;gt;0.05). These results suggested the ratio of basal insulin dose to TDD might be decreased while eGFR declined in patients with type 2 diabetic nephropathy. Disclosure S. Lin: None. K. Zhang: None. P. Li: None. K. Fang: None. L. Zeng: None. Funding Science and Technology Planning Project of Guangdong Province (2017A020215026); Medical Scientific Research Foundation of Guangdong Province (A2017314) </jats:sec

Adrenal Hemorrhage in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome: A Case Report and Literature Review

Antiphospholipid syndrome (APS) is an autoimmune disorder while adrenal hemorrhage could be its rare complication. Herein, we report the case of a 32-year-old unmarried woman with a history of systemic lupus erythematosus (SLE) who was hospitalized after complaints of upper abdominal pain, limb weakness, and loss of appetite for 2 weeks. Laboratory examination revealed hyponatremia, low plasma cortisol levels, increased adrenocorticotropic hormone levels, and a positive anticardiolipin antibody status. Furthermore, computed tomography (CT) revealed the presence of bilateral adrenal masses. Ultimately, based on dynamic changes in CT images, these masses were diagnosed as adrenal hemorrhage owing to APS. A computer-assisted literature search was conducted to identify cases of primary adrenal insufficiency associated with APS and/or SLE. The clinical features, laboratory examination, treatments, and outcomes of these cases were summarized. Our findings emphasize the importance of screening for adrenal insufficiency in patients with SLE or APS who present with abdominal complaints, asthenia, and hyponatremia. It is also recommended to test for APS all patients with adrenal hemorrhage