Archives of Endocrinology Metabolism最新文献

{"title":"Early expression of neuroinflammation in an untreated fatal case of diabetic ketoacidosis.","authors":"Carol M Artlett, Sabri H Abdelwahab, William H Hoffman, Ali S Calikoglu","doi":"10.20945/2359-4292-2024-0074","DOIUrl":"https://doi.org/10.20945/2359-4292-2024-0074","url":null,"abstract":"<p><p>We present the case of a young adult who had lethargy and significant weight loss for the three weeks before his death. The history of the present illness suggested a prodrome of several weeks, with progressive weakness indicating an advancing metabolic decompensation. To our knowledge, this is the first study performed on human brain tissue with type 1 diabetes (T1D) and likely diabetic ketoacidosis (DKA) before treatment. We studied neuroinflammatory markers in an insulin-deficient state without treatment compared with those found in a treated patient with T1D/DKA of similar age and race who died shortly after treatment. The frontal cortex and hippocampus were stained for tight junction proteins, RAGE, NLRP3, and HMGB1. Other markers that can disrupt the blood-brain barrier, such as IL-17, IL-6, IL-1β, GFAP, and IL-10 were also tested. This case study reveals that neuroinflammatory markers are expressed in the DKA brain at a lower level before treatment than those found to be expressed in the brain after treatment. These findings suggest that in DKA, dehydration minimizes inflammation which could be exacerbated with fluids promoting neuroinflammation and cognitive deficits. These findings require further studies and could identify therapeutic targets to reduce the progression of neuroinflammation and brain edema.</p>","PeriodicalId":54303,"journal":{"name":"Archives of Endocrinology Metabolism","volume":"68 ","pages":"e240074"},"PeriodicalIF":1.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142636193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the correlation between lipids related to cardiovascular risk factors and small dense LDL particles in patients with type 2 diabetes.","authors":"Alena Viktorinova, Robert Brnka, Margita Pirosova, Peter Pontuch, Sona Kinova","doi":"10.20945/2359-4292-2024-0069","DOIUrl":"10.20945/2359-4292-2024-0069","url":null,"abstract":"<p><strong>Objective: </strong>Sex differences in lipid metabolism associated with prevalent small dense (S-) low-density lipoprotein (LDL) cholesterol particles are not elucidated. An LDL to apolipoprotein B (ApoB) ratio < 1.2 can estimate how prevalent S-LDL particles are and, thus, reflect cardiovascular risk. The aim of this study was to evaluate the sex distribution of LDL/ApoB ratio among patients with type 2 diabetes (DM) and to assess, in both sexes, the correlations between key lipid parameters and LDL/ApoB < 1.2.</p><p><strong>Subjects and methods: </strong>The study included 190 Caucasian participants (mean age 51.8 ± 6.4 years) with DM (DM group) or without DM (control group) divided into subgroups according to sex. The participants were examined for levels of several lipid parameters, selected lipid-related oxidative stress markers, and estimated S-LDL prevalence.</p><p><strong>Results: </strong>An LDL/ApoB < 1.2 (p < 0.05) was observed in 67% of male and female patients with DM. Although triglyceride levels did not differ between men and women, women had higher levels of total cholesterol (p < 0.05) and LDL cholesterol (p < 0.01) than men. Among women with LDL/ApoB < 1.2, strong correlations were observed between values of lipid hydroperoxides (LOOH) and atherogenic index of plasma (p < 0.005) and between levels of triglycerides and LOOH (p < 0.005) and ApoB (p < 0.0001).</p><p><strong>Conclusions: </strong>The findings indicate that women with LDL/ApoB < 1.2 tend to have a higher cardiovascular risk than men. Additionally, LDL/ApoB < 1.2 can be a surrogate marker for estimating the S-LDL prevalence in individuals with potentially increased cardiovascular risk.</p>","PeriodicalId":54303,"journal":{"name":"Archives of Endocrinology Metabolism","volume":"68 ","pages":"e240069"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accuracy of novel anthropometric indices for assessing the risk for progression of prediabetes to diabetes; 13 years of results from Isfahan Cohort Study.","authors":"Mohammad Fakhrolmobasheri, Davood Shafie, Behrad Manshaee, Shima Karbasi, Alireza Mazroui, Mahsa Mohammadi Najafabadi, Sadegh Mazaheri-Tehrani, Masoumeh Sadeghi, Hamidreza Roohafza, Maryam Emamimeybodi, Maryam Heidarpour, Najmeh Rabanipour, Nizal Sarrafzadegan","doi":"10.20945/2359-4292-2023-0269","DOIUrl":"10.20945/2359-4292-2023-0269","url":null,"abstract":"<p><strong>Objective: </strong>We examined the accuracy of novel anthropometric indices in predicting the progression of prediabetes to diabetes.</p><p><strong>Subjects and methods: </strong>This study was performed on the pre-diabetic sub-population from Isfahan Cohort Study (ICS). Participants were followed up from 2001 to 2013. During every 5-year follow-up survey, patients' data regarding the incidence and time of incidence of diabetes were recorded. We evaluated the association between the risk of developing diabetes and novel anthropometric indices including: visceral adiposity index (VAI), lipid accumulation products (LAP), deep abdominal adipose tissue (DAAT), abdominal volume index (AVI), A body shape index (ABSI), body roundness index (BRI) and weight-adjusted waist index (WWI). We categorized the indices into two groups according to the median value of each index in the population. We used Cox regression analysis to obtain hazard ratios (HR) using the first group as the reference category and used receiver operating characteristics (ROC) curve analysis for comparing the predictive performance of the indices.</p><p><strong>Results: </strong>From 215 included subjects, 79 developed diabetes during the 13-year follow-up. AVI, LAP, BRI, and VAI indicated statistically significant HR in crude and adjusted regression models. LAP had the greatest association with the development of diabetes HR = 2.18 (1.36-3.50) in multivariable analysis. ROC curve analysis indicated that LAP has the greatest predictive performance among indices (area under the curve = 0.627).</p><p><strong>Conclusion: </strong>Regardless of baseline confounding variables, prediabetic patients with a higher LAP index may be at significantly higher risk for developing diabetes.</p>","PeriodicalId":54303,"journal":{"name":"Archives of Endocrinology Metabolism","volume":"68 ","pages":"e230269"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active surveillance of papillary thyroid carcinoma in Latin America: a scoping review.","authors":"Pedro Garnier Manfio, Lucas Albuquerque Chinelatto, Flávio Carneiro Hojaij","doi":"10.20945/2359-4292-2023-0495","DOIUrl":"https://doi.org/10.20945/2359-4292-2023-0495","url":null,"abstract":"<p><p>Thyroid nodules are a very common finding and have a malignancy rate of 7%-15%. Some malignant nodules have an indolent behavior and may not affect mortality if left untreated. Active surveillance (AS) is a strategy to prevent overtreatment in patients with papillary thyroid microcarcinomas (PTMCs). This review was conducted to evaluate the status of AS for low-risk PTMC in Latin America, including cultural and logistical challenges, disease progression data, and financial viability. We searched PubMed (MEDLINE), SciELO, LILACS, and Web of Science for articles published after 2014 and enrolling adult Latin American patients. Articles cited in the selected studies were also retrieved. We analyzed the AS protocols, technical or logistical challenges, patient adherence, reasons for AS interruption, surgical conversion rates, duration of AS, and disease progression during AS in our region. Three articles were included in the analysis, all of which considered AS a viable option and reported tumor progression and outcomes similar to those reported in other countries. Neck ultrasound and serum levels of thyroglobulin, thyroid-stimulating hormone (TSH), thyroxine (T4), and antithyroglobulin antibodies were included in the follow-up. No cases of new distant metastases were reported, and the outcomes were favorable when surgery was required. Anxiety was the main reason for AS interruption. We conclude that AS can be an acceptable approach and is safe and effective in Latin America, although more prospective studies are needed to consolidate this strategy in our region. Adequate infrastructure, follow-up, and patient education, as well as multidisciplinary healthcare teams trained in conducting AS must be ensured for successful results.</p>","PeriodicalId":54303,"journal":{"name":"Archives of Endocrinology Metabolism","volume":"68 ","pages":"e230495"},"PeriodicalIF":1.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights from a Wolfram syndrome cohort: clinical and molecular findings from a specialized diabetes reference center.","authors":"Carolina Paniago Lopes, Gentil Ferreira Gonçalves, Maria Fernanda Vanti Macedo Paulino, Adriana Mangue Esquiaveto-Aun, Maricilda Palandi de Mello, Elizabeth João Pavin, Ikaro Soares Santos Breder, Mariana Zorron Mei Hsia Pu, Sofia Helena Valente de Lemos-Marini, Gil Guerra","doi":"10.20945/2359-4292-2024-0091","DOIUrl":"https://doi.org/10.20945/2359-4292-2024-0091","url":null,"abstract":"<p><strong>Objective: </strong>Considering the rarity and clinical and molecular diversity of Wolfram syndrome (WS), the objective of this study was to identify patients with a clinical presentation suggestive of WS following up at a single Brazilian diabetes service and analyze their clinical and molecular characteristics.</p><p><strong>Subjects and methods: </strong>The study included all patients with a clinical presentation of WS following up between 1991 and 2022 with early-onset diabetes mellitus and other WS signs and symptoms. A retrospective analysis was conducted, including patients' age, sex, consanguinity, age at symptom onset, diagnosis of diabetes mellitus, optic atrophy, diabetes insipidus, neurological and psychiatric disorders, hearing loss, urinary disorders, hypogonadism, and <i>WFS1</i> molecular analysis.</p><p><strong>Results: </strong>Eight patients were identified, all of whom were diagnosed with diabetes mellitus at an average age of 3.7 years. Optic atrophy, diabetes insipidus, and hearing loss were common, while psychiatric and neurological alterations were observed in some cases. Genetic analysis revealed pathogenic variants in homozygosity or compound heterozygosity. The most frequent variant was p. Val412Serfs29, present in five of the seven families.</p><p><strong>Conclusions: </strong>This study represents the second-largest Brazilian sample of WS and is the first cohort from a single center in Southeast Brazil. The patients had an early, severe, and complete clinical presentation. The genetic variants identified were consistent with previous literature descriptions. The variant p. Val412Serfs29 was particularly common in this cohort, highlighting its relevance in the region.</p>","PeriodicalId":54303,"journal":{"name":"Archives of Endocrinology Metabolism","volume":"68 ","pages":"e240091"},"PeriodicalIF":1.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Follicular cell-derived thyroid carcinomas harboring novel genetic <i>BRAF^NON-V600E</i> mutations: real-world data obtained using a multigene panel.","authors":"Juliana Lima von Ammon, Gabriel Jeferson Rodríguez Machado, Rafael Reis Campos da Matta, Ana Clara Telles, Fabiane Carrijo, Bruno Alexsander França Dos Santos, Juliana Cabral Duarte Brandão, Thiago Magalhães da Silva, Fabio Hecht, Gabriel Avela Colozza-Gama, Julia Helena Tezzei, Janete Maria Cerutti, Helton Estrela Ramos","doi":"10.20945/2359-4292-2024-0067","DOIUrl":"10.20945/2359-4292-2024-0067","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the molecular profile of follicular cell-derived thyroid carcinomas (FCDTCs) and correlate the identified mutations with the clinical and pathological features of the affected patients.</p><p><strong>Materials and methods: </strong>Cross-sectional study of tumor samples from 100 adult patients diagnosed with FCDTC between 2010 and 2019. The patients' clinical and pathological data were collected. Genomic DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumors using the ReliaPrep FFPE gDNA Miniprep System. Genotyping of target genomic regions (<i>KRAS, NRAS, BRAF, EGFR</i>, and <i>PIK3CA</i>) was performed using the AmpliSeq panel, while sequencing was performed on the iSeq 100 platform.</p><p><strong>Results: </strong>The patients' mean age was 39 years. In all, 82% of the tumors were classic papillary thyroid carcinomas. Overall, 54 (54%) tumor samples yielded satisfactory results on next-generation sequencing (NGS), of which 31 harbored mutations. <i>BRAF</i> gene mutations were the most frequent, with the <i>BRAF</i> ^V600E mutation present in 10 tumors. Seven tumors had <i>BRAF</i> ^NON-V600E mutations not previously described in FCDTCs (G464E, G464R, G466E, S467L, G469E, G596D, and the T599Ifs*10 deletion) but described in other types of cancer (<i>i.e.</i>, skin/melanoma, lung, colorectal, and others). One tumor had a previously reported <i>BRAF</i> ^A598V mutation. <i>EGFR</i> gene mutations were found in 16 (29%) and <i>KRAS</i> or <i>NRAS</i> alterations in 8 (14%) of the 54 tumors analyzed.</p><p><strong>Conclusion: </strong>We described herein seven non-hotspot/novel variants in the <i>BRAF</i> gene, highlighting their potential role in expanding our understanding of FCDTC genetics.</p>","PeriodicalId":54303,"journal":{"name":"Archives of Endocrinology Metabolism","volume":"68 ","pages":"e240067"},"PeriodicalIF":1.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of liraglutide after bariatric surgery: a 36-month follow-up in a real-world setting in Chile.","authors":"María Magdalena Farías","doi":"10.20945/2359-4292-2023-0234","DOIUrl":"10.20945/2359-4292-2023-0234","url":null,"abstract":"<p><strong>Objective: </strong>Bariatric surgery has several benefits, including sustainable weight loss and improvement or resolution of metabolic comorbidities. However, despite initially successful weight loss, weight regain occurs during long-term follow-up, and many patients are unable to reach or maintain their target weight goals. Liraglutide is a therapy for obesity aimed at preventing weight regain.</p><p><strong>Materials and methods: </strong>This retrospective, observational, single-arm, pre-post study was performed to analyze the relative change in body weight among patients receiving liraglutide after bariatric surgery in a real-world setting in Chile.</p><p><strong>Results: </strong>Treatment with liraglutide at a median dose of 1.2 mg was associated with a mean weight loss from baseline to 3, 6, 12, 24, and 36 months of 5%, 7.7%, 7.6%, 5.8%, and 5.1%, respectively. The mean body mass index reduction was 14.8% at 36 months. Dropout rates were consistent with those of usual obesity treatments. Overall, 70% of the patients were receiving other weight-loss drugs. Liraglutide was well tolerated, but cost barriers led to several patients interrupting its use.</p><p><strong>Conclusion: </strong>Liraglutide is an effective and safe treatment for weight reduction after bariatric surgery in patients receiving routine clinical care in Chile.</p>","PeriodicalId":54303,"journal":{"name":"Archives of Endocrinology Metabolism","volume":"68 ","pages":"e230234"},"PeriodicalIF":1.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Usefulness of prolactin levels in predicting the etiology of hyperprolactinemia in a cohort of 770 patients.","authors":"Lucio Vilar, Clarice Freitas Vilar, Ruy Lyra, Luciano Albuquerque, Ana Carolina Thé Garrido, Patrícia Sampaio Gadelha, Erik Trovão Diniz, Marcos Almeida, Lucia Helena Cordeiro, Erico Higino de Carvalho, Ana Teresa Bezerra de Melo, Karoline Matias Medeiros, Gabriel Rodrigues de Assis Ferreira, José Coelho Mororó, Daniela Zago Ximenes, Camila Ribeiro Coutinho Madruga, Rosália de Oliveira Nunes, Yanna Queiroz Pereira de Sá, Luciana Ansaneli Naves","doi":"10.20945/2359-4292-2023-0391","DOIUrl":"https://doi.org/10.20945/2359-4292-2023-0391","url":null,"abstract":"<p><strong>Objective: </strong>Determining the etiology of hyperprolactinemia is fundamental for selecting the most appropriate treatment strategy. The aim of this study was to evaluate the usefulness and accuracy of prolactin levels in predicting the etiology of nonphysiological hyperprolactinemia.</p><p><strong>Subjects and methods: </strong>In this retrospective study, we reviewed medical records of patients with nonphysiological hyperprolactinemia seen at two neuroendocrine reference centers located in Recife, Brazil, from January 2000 to December 2019.</p><p><strong>Results: </strong>The study included 770 patients aged 12-73 years (65% female). The three most frequent etiologies of hyperprolactinemia were prolactinomas (n = 263; 34.2%), drug-induced hyperprolactinemia (n = 160; 20.8%), and macroprolactinemia (n = 120; 15.6%). The highest mean prolactin levels were observed in cases of prolactinomas and idiopathic hyperprolactinemia. Most patients with hyperprolactinemia due to other etiologies had prolactin levels < 100 ng/mL, but these levels were also found in 16.5% of patients with microproplactinomas and in 20% of those with idiopathic hyperprolactinemia. Likewise, prolactin levels largely overlapped among patients with microprolactinomas, macroprolactinemia, and drug-induced hyperprolactinemia. Notably, prolactin levels > 250 ng/mL enabled a clear distinction between the etiologies of macroprolactinoma and nonfunctioning pituitary adenoma. Moreover, prolactin levels > 500 ng/mL were highly suggestive of macroprolactinomas, although they were also found in very few patients (<2%) with microprolactinomas or drug-induced hyperprolactinemia.</p><p><strong>Conclusion: </strong>Despite considerable overlap in prolactin levels among the different etiologies of hyperprolactinemia, values > 250 ng/mL allowed a clear distinction between macroprolactinomas and nonfunctioning pituitary adenomas. Furthermore, prolactin levels > 500 ng/mL were almost exclusively found in patients with prolactinomas.</p>","PeriodicalId":54303,"journal":{"name":"Archives of Endocrinology Metabolism","volume":"68 ","pages":"e230391"},"PeriodicalIF":1.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of once-daily oral orforglipron on weight and metabolic markers: a systematic review and meta-analysis of randomized controlled trials.","authors":"Carine Lütkemeyer, Eric Pasqualotto, Rafael Oliva Morgado Ferreira, Matheus Pedrotti Chavez, Ilmar Petris, Henrique Vilar Dos Santos, Julia Murbach Wille, Alexandre Hohl, Marcelo Fernando Ronsoni, Simone van de Sande-Lee","doi":"10.20945/2359-4292-2023-0469","DOIUrl":"https://doi.org/10.20945/2359-4292-2023-0469","url":null,"abstract":"<p><p>The aim of this study is to assess the effects of once-daily oral orforglipron on weight and metabolic markers in adult patients. PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were systematically searched until February 2024 for randomized controlled trials (RCTs) comparing orforglipron versus placebo or other anti-obesity medications in adult patients. Weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) or risk differences for binary endpoints were computed, with 95% confidence intervals (CIs). Heterogeneity and risk of bias were assessed with I² statistics and Rob-2, respectively. Statistical analyses were performed using R, version 4.2.2. A total of four studies were included, comprising 815 patients, of whom 620 (76.1%) were prescribed orforglipron. Compared with placebo, orforglipron reduced body weight (WMD -6.14 kg, 95% CI -9.62 to -2.66 kg), body mass index (WMD -2.87 kg/m², 95% CI -4.65 to -1.10 kg/m²), and waist circumference (WMD -5.32 cm, 95% CI -9.13 to -1.51 cm). More patients treated with orforglipron than placebo achieved a weight loss of ≥ 5% (RR 3.31, 95% CI 2.23-4.93), ≥ 10% (RR 5.24, 95% CI 2.07-13.31), and ≥ 15% (RR 9.53, 95% CI 1.26-71.89). The most common adverse events were related to the gastrointestinal tract. In this meta-analysis, the use of once-daily oral orforglipron by adult patients was associated with a significant decrease in body weight, as compared with placebo, with an increase in non-severe gastrointestinal adverse events. Phase 3 RCTs are expected to shed further light on the efficacy and safety of once-daily oral orforglipron over the long term.</p>","PeriodicalId":54303,"journal":{"name":"Archives of Endocrinology Metabolism","volume":"68 ","pages":"e230469"},"PeriodicalIF":1.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GDF-15 levels in patients with polycystic ovary syndrome treated with metformin: a combined clinical and in silico pathway analysis.","authors":"Fernanda M V Magalhães, Rodrigo M C Pestana, Cláudia N Ferreira, Ieda F O Silva, Ana L Candido, Flávia R Oliveira, Fernando M Reis, Karina B Gomes","doi":"10.20945/2359-4292-2023-0416","DOIUrl":"10.20945/2359-4292-2023-0416","url":null,"abstract":"<p><strong>Objective: </strong>Polycystic ovary syndrome (PCOS) is an endocrine disease characterized by metabolic, reproductive, and psychological manifestations. Growth and differentiation factor 15 (GDF-15) is a cytokine associated with metabolic and inflammatory disorders. Metformin is commonly used for the treatment of PCOS. We investigated the relationship between GDF-15 levels and PCOS, the effect of metformin on GDF-15 levels, and potential biologic pathways related to GDF-15.</p><p><strong>Subjects and methods: </strong>The study included 35 women with PCOS and 32 women without PCOS (controls). Both groups were compared in terms of GDF-15 levels. Additional analysis was conducted on samples from 22 women with PCOS who were treated with either metformin (n = 7) or placebo (n = 15), retrieved from a previous randomized, controlled trial. Levels of GDF-15 were measured using MILLIPLEX. The biologic pathways related to GDF-15 were evaluated using the databases STRING, SIGNOR, and Pathway Commons. The statistical analysis was conducted using the software SPSS.</p><p><strong>Results: </strong>Levels of GDF-15 were higher in the PCOS group compared with the non-PCOS group (p = 0.039). Among women with PCOS, GDF-15 levels were higher in those treated with metformin compared with placebo (p = 0.007). The proteins related to GDF-15 overlapped between the databases, and a significant interaction was found between GDF-15 and proteins related to PCOS and its complications, including those related to estrogen response, oxidative stress, ovarian infertility, interleukin (IL)-18, IL-4, the ratio of advanced glycation end products to their receptor (AGE/RAGE), leptin, transforming growth factor beta (TGF-β), adipogenesis, and insulin.</p><p><strong>Conclusion: </strong>The findings of the present study suggest a relationship between GDF-15 and PCOS and a potential increase in GDF-15 levels with metformin treatment. An additional finding was that GDF-15 could be involved in biologic pathways related to PCOS complications.</p>","PeriodicalId":54303,"journal":{"name":"Archives of Endocrinology Metabolism","volume":"68 ","pages":"e230416"},"PeriodicalIF":1.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}