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Thyroid hormones, thyroxin (T4) and the biologically active triiodothyronine (T3), play important roles in liver metabolic regulation, including fatty acid biosynthesis, beta-oxidation, and cholesterol homeostasis. These functions position TH signaling as a potential target for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Elevated T3 levels in the circulation are associated with increased hepatic lipid turnover, which is also under the control of the circadian clock system. In this study, we developed a cell system to study the impact of hepatocyte circadian rhythms on the metabolic response to T3 treatment under control and steatotic conditions. Synchronized AML-12 circadian reporter hepatocytes were treated with T3 at different circadian phases and metabolic conditions. T3 treatment increased metabolic activity in a dose-independent fashion and had no significant effect on circadian rhythms in AML-12 cells. T3 had marked time-of-treatment-dependent effects on metabolic transcript expression. Steatosis induction altered metabolic transcript expression in AML-12 cells. In this condition, the circadian rhythm period was lengthened, and this effect was independent of T3. Under steatotic conditions, T3 had marked time-of-treatment dependent effects on metabolic transcript expression, which differed from those observed under control conditions. These findings reveal a time-of-day-dependent response of hepatocytes to T3, which is further modulated by the metabolic state. Our data suggest that time has a strong influence on liver TH action, which might be considered when treating MASLD. [ABSTRACT FROM AUTHOR]

The current study examined the effects of official chess competition on salivary cortisol and mood swings in adolescent girls. Fourteen girl competitive chess players participated in the 5-day Swiss chess tournament held in nine heavy and light rounds. The tournament was performed at 9:00 a.m. (first, third, fifth, seventh, and ninth rounds) and 3:00 p.m. (second, fourth, sixth, and eighth rounds). Salivary cortisol and mood was measured before the tournament, before and after the second, fourth, sixth, and eighth rounds, and following the tournament (10 samples). The resting levels of salivary cortisol had considerably greater values on the first, second, third, and fourth competition days compared to 1 week before the competition (P = 0.001). The post-competition cortisol concentration was significantly higher on the second and third days than before the competition (P = 0.001). Winners had considerably higher levels of salivary cortisol compared to losers (P = 0.001). There was a significant increase in total mode disturbance (P = 0.001), anger (P = 0.009), and tension (P = 0.045) following heavy rounds (second and third day) compared to the values before the competition. At the same time, the Scores of vigor decreased significantly (P = 0.001). The findings of the present study showed participating in the official chess competition increased salivary cortisol and caused negative alterations in mood components associated with the difficulty and outcome of the match, indicating the psychological stress. Hence, psychological interventions can be used for psychological recovery of competitive chess players after the competition. [ABSTRACT FROM AUTHOR]

Summary: Anti‐Müllerian hormone (AMH) is commonly used as a marker of ovarian reserve. Although obesity is associated with decreased fertility, the relationship between body mass index (BMI) and AMH remains uncertain, hindering the accurate interpretation of AMH. We sought to assess the relationship between serum AMH and BMI in patients with and without polycystic ovarian syndrome (PCOS). This study analysed 500 patients at a single centre between 2020 and 2021. Patients were divided into cohorts: those with BMI <40 kg/m2 and those with BMI >40 kg/m2. Patients with and without PCOS were included. Chi‐square tests, Fisher's exact tests, multiple linear regression analysis and independent t‐tests were performed as appropriate. In the general study population, serum AMH was not significantly different in the BMI >40 kg/m2 group compared to the BMI <40 kg/m2 group (4.3 ± 5.6 vs. 4.3 ± 5.6, p =.35). Patient ages between these two groups differed, with an average age of 35.4 ± 5.4 years in the BMI <40 kg/m2 group and 33.7 ± 5.4 years in the BMI <40 kg/m2 group (p =.031). Our multivariate regression analysis, which adjusted for age, demonstrated a significant interaction effect between BMI and PCOS diagnosis, indicating that the relationship between BMI and AMH is dependent on PCOS status (β = −.03, 95% confidence interval [CI]: −0.05, 0.00, p =.044). In patients without PCOS, we found a non‐significant relationship between AMH and BMI (β =.00, 95% CI −0.01, 0.01, p =.7); however, in patients with PCOS, AMH significantly decreased as BMI increased (β = −.03, 95% CI −0.06, 0.00, p =.034). BMI has an inverse association with AMH levels in patients with PCOS, indicating a need for future research to determine if that interaction represents a clinically significant negative effect on reproductive function. [ABSTRACT FROM AUTHOR]

Objective: To investigate the metabolic, cardiovascular, and neuropsychological phenotype, quality of life (QoL), and hormonal regulation in individuals with congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired synthesis of cortisol in the adrenal cortex and, if untreated compensatory hyperandrogenism. CAH is associated with an increased cardiovascular and metabolic morbidity, possibly due to overtreatment with glucocorticoids, leading to weight gain, insulin resistance, and metabolic syndrome. Design, Participants, Measurements: Thirty‐seven individuals with CAH and 33 age‐ and sex‐matched controls were evaluated at a single centre at Aarhus University Hospital with echocardiography, electrocardiogram, 24‐h blood pressure, biochemistry, anthropometrics, and autism spectrum, anxiety, depression, personality, cognitive failures, and QoL were assessed using questionnaires. Results: CAH individuals had lower height than controls (170.5 vs. 182.9 cm in males and 160.2 vs. 170.1 cm in females, p < 0.01). Compared with female controls, females with CAH had higher haemoglobin (8.8 vs. 8.2 mmol/L, p = 0.003) and BMI (29.7 vs. 25.5 kg/m2, p = 0.006), reduced insulin sensitivity (HOMA‐IR): 2.7 vs. 1.9, p = 0.018), prolonged E‐wave deceleration time (193 vs. 174 cm, p = 0.015), and E/é ratios (5.4 vs. 4.5, p = 0.017), and lower self‐reported QoL. Males with CAH had more cognitive complaints (p = 0.034) and higher autistic scores (19.9 vs. 14.9; p = 0.068) compared with male controls. More individuals with CAH than controls reported writing problems. Conclusion: A sex‐specific comorbidity profile is evident in CAH, with females presenting with decreased metabolic and overall self‐reported health, whereas males with CAH presented with increased cognitive complaints and autistic traits. [ABSTRACT FROM AUTHOR]

Thyroid hormones influence multiple systems, but most often the impact on the cardiovascular system is what brings the patient to the emergency department. Basedow's disease, an autoimmune condition, is one of the most common causes of hyperthyroidism. The purpose of this presentation is to raise attention to an extracardiac cause that can lead to cardiac failure. A 55-year-old woman presented to our cardiology service with rapid palpitations, shortness of breath on small efforts, and extreme fatigue. The electrocardiogram revealed sinus tachycardia with a heart rate of 144 beats per min. Paraclinical investigations and a multidisciplinary team consultation led to a diagnosis of thyrotoxicosis due to Basedow's disease. Following the initiation of cardiological and endocrinological treatments, the patient's condition improved. Although hyperthyroidism is an extracardiac cause, it brought the patient to the cardiology emergency service for heart failure symptoms. The key to achieving a correct diagnosis and determining an optimal treatment lies in the multidisciplinary approach of pathology. [ABSTRACT FROM AUTHOR]

Endocrine physiology is a complex subject for students. Game-based learning (GBL) and case-based learning (CBL) are active methodologies that are widely used because of their potential for motivation and greater proximity to the reality of modern students. We evaluated the effectiveness of GBL and CBL among veterinary medicine students compared with a control group using peer tutoring. Students (n = 106) from two institutions volunteered to participate in this study. The participants were submitted to a pretest questionnaire and subsequently were divided into three paired groups by their performance on the pretest exam: 1) traditional class + peer tutoring, 2) traditional class + GBL, and 3) traditional class + CBL. After the students completed the activities, their performance was once again evaluated by applying a new test with the same initial 10 questions and another set of 10 different questions. The students' perceptions and satisfaction with the methodologies and learning strategies were assessed. Anxiety was assessed with the State-Trait Anxiety Inventory before and after the conventional class and after the active methodologies. The GBL group significantly improved their correct answers compared with the baseline (P < 0.05), with no significant difference from CBL and peer tutoring. Anxiety levels did not differ regardless of the time of evaluation or the teaching methodology applied. GBL promoted a greater perception of the stimulus for self-study and problem-solving ability and contributed to the development of group dynamics compared with the group who received CBL (P < 0.05). In conclusion, GBL showed better results than peer tutoring and CBL. NEW & NOTEWORTHY: We compared the supplementary use of game-based learning, case-based learning, and peer tutoring in the study of endocrine physiology by veterinary students and observed a slight advantage for game-based learning over the other two methodologies. The game was developed by the authors and is an unprecedented tool that can prove useful to improve knowledge acquisition in students of veterinary medicine. Thus, game-based learning is an effective supplementary teaching strategy. [ABSTRACT FROM AUTHOR]

Maturity-onset diabetes of young ‘MODY’ type 6 is a rare form of monogenic diabetes caused by mutations in neuronal differentiation 1 (NEUROD1). Clinical features vary in a large spectrum in terms of age and body mass index (BMI) at diagnosis. Here, we reported the youngest patient with a NEUROD1 variant to the best of our knowledge. A 2.1-year-old girl was referred to pediatric endocrinology clinic for elevated fasting BG (104 mg/dL) which was detected at another center where she had been evaluated for loss of appetite. Her maternal aunt and uncle had been diagnosed with type 2 diabetes mellitus (DM) at the age of 40 and 45 years; they were obese (BMI: 30.2 and 30.6 kg/m² ). At the age of 3.7 years old, she was hospitalized for buccal cellulitis and plasma glucose concentration was 239 mg/dL at admission. Targeted next-generation sequencing (NGS) was performed considering the stress induced hyperglycemia without serious illness, negative islet cell antibodies and insulin autoantibodies, age at the presentation, and family history of DM. NGS analysis revealed a previously reported heterozygous missense variant in NEUROD1. Segregation studies showed that the identified variant was inherited from her 44-year-old mother with a BMI of 27.2 kg/m² and a normal oral glucose tolerance test. Heterozygous NEUROD1 mutations cause low-penetrant diabetes that is heterogeneous in terms of clinical features as some patients fulfill the classic MODY definition and others are mimicking type 2 DM. Clinical manifestations and family history should be carefully evaluated in patients with stress induced hyperglycemia to identify candidate cases for molecular testing, and proper follow-up should be initiated in affected individuals. [ABSTRACT FROM AUTHOR]

Maturity onset diabetes of the young (MODY) is characterized by noninsulin-dependent diabetes diagnosed before the age of 25 years with an autosomal dominant inheritance. Rare mutations in the hepatocyte nuclear factor-1-beta (HNF1B) gene produce a syndrome that resembles MODY. About half of patients diagnosed with MODY type 5 due to HNF1B variants, carry a whole gene deletion, known as 17q12 deletion syndrome. 17q12 deletion syndrome is a rare chromosomal anomaly and is typified by deletion of more than 15 genes, including HNF1B resulting in kidney abnormalities and renal cysts, a diabetes syndrome and neurodevelopmental or neuropsychiatric disorders. A 12-year-old girl was referred after high blood sugar was detected in the hospital where she presented with polyuria and polydipsia, which had persisted for one month. Her serum magnesium (Mg) level was low at 1.5 mg/dL (normal value 1.6-2.6) and glycated hemoglobin was 14% (normal value 3.6-5.8) concurrent with a c-peptide of 1.54 ng/mL (normal value 0.8-4). MODY5 was suspected but the NGS gene panel (ABCC8, BLK, CEL, GCK, HNF1A, HNF1B, HNF4A, INS, KCNJ11, KLF11, NEURODD1, PAX4, PDX1, RFX6, ZFP57, GLIS3, FOXP3, NEUROG3, G6PC2) did not identify any abnormality. During follow-up, her serum Mg remained low (1.2 mg/ dL) together with elevated urinary Mg excretion at 172.5 mg/day. An HNF1B variant was again suspected in a patient with chronic hypomagnesemia with normal basal C peptide level. Abdominal computed tomography and magnetic resonance imaging revealed a 43 mm diameter, cystic lesion in the head of the pancreas, with agenesis of the pancreatic neck, trunk and tail. Genetic testing using a microarray analysis was subsequently performed and a heterozygous deletion at 17q12, including HNF1B, was detected. In case of clinical suspicion of HNF1B variants, further genetic examination using other techniques such as MLPA and CGH array may be required to detect the variant. This is because deletions and duplications may not be detected using next generation screening panel techniques. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) holds the promise of addressing many of the numerous challenges healthcare faces, which include a growing burden of illness, an increase in chronic health conditions and disabilities due to aging and epidemiological changes, higher demand for health services, overworked and burned-out clinicians, greater societal expectations, and rising health expenditures. While technological advancements in processing power, memory, storage, and the abundance of data have empowered computers to handle increasingly complex tasks with remarkable success, AI introduces a variety of meaningful risks and challenges. Among these are issues related to accuracy and reliability, bias and equity, errors and accountability, transparency, misuse, and privacy of data. As AI systems continue to rapidly integrate into healthcare settings, it is crucial to recognize the inherent risks they bring. These risks demand careful consideration to ensure the responsible and safe deployment of AI in healthcare. [ABSTRACT FROM AUTHOR]

In endocrinology, the types and quantity of digital data are increasing rapidly. Computing capabilities are also developing at an incredible rate, as illustrated by the recent expansion in the use of popular generative artificial intelligence (AI) applications. Numerous diagnostic and therapeutic devices using AI have already entered routine endocrine practice, and developments in this field are expected to continue to accelerate. Endocrinologists will need to be supported in managing AI applications. Beyond technological training, interdisciplinary vision is needed to encompass the ethical and legal aspects of AI, to manage the profound impact of AI on patient/provider relationships, and to maintain an optimal balance between human input and AI in endocrinology. [ABSTRACT FROM AUTHOR]

Background: Ramadan Intermittent Fasting (RIF) has the potential to alter hormonal levels in the body. This study investigates the impact of RIF on hormonal levels among healthy individuals during Ramadan. Methods: A systematic review and meta-analysis of previously published studies were conducted, focusing on healthy non-athlete adults. The intervention examined was Ramadan Intermittent Fasting, and the primary outcomes assessed were changes in endocrine hormonal and biochemical parameters. The pooled effect measure was expressed as odds ratio (OR) and 95% confidence interval (CI) using the random-effects model. Results: A total of 35 original articles were retrieved, with a combined sample size of 1,107 participants eligible for the meta-analysis. No significant relationship was found between pre- and post-Ramadan hormonal levels of T3, T4, TSH, FT3, FT4, Testosterone, LH, FSH, Prolactin, PTH, Calcium, and Phosphorus (P-value<0.05). However, a substantial decrease in morning cortisol levels was observed across the studies (P-value: 0.08, Hedges' g = -2.14, 95% CI: -4.54, 0.27). Conclusions: Ramadan Intermittent Fasting results in minimal hormonal changes and is a safe practice for healthy individuals. The fasting regimen appears to disrupt the circadian rhythm, leading to a decrease in morning cortisol levels. [ABSTRACT FROM AUTHOR]

Background: Health‐related quality‐of‐life (HRQoL) assessment tools are becoming increasingly important for the assessment of diseases in veterinary medicine. Objectives: To develop a tool to assess the HRQoL of hyperthyroid cats and their owners. Animals: Cats with hyperthyroidism (n = 229) and without hyperthyroidism (n = 322). Methods: Cross‐sectional study design. A preliminary list of 28 questions relating to the HRQoL of hyperthyroid cats and the influence their cat's disease might have on owners was created. Each question consisted of 2 subquestions: (1) "how often does the item apply"; (2) "how strongly does the item affect HRQoL." The questionnaire was refined based on statistical analysis, including Mann‐Whitney‐U tests on each item, comparing the results from cats with and without hyperthyroidism. Internal consistency and reliability of the questions were measured by Cronbach's alpha (α). P <.05 was considered significant. Results: Overall, 25/28 questions were retained within the final HRQoL tool, which had an excellent internal consistency (α =.92). The tool produced a score between 0 and 382 (lower scores meaning better HRQoL). The median HRQoL score was 87.5 (range, 2‐348) for cats with hyperthyroidism, and 27 (range, 0‐249) for cats without (P <.001), suggesting the HRQoL was poorer in hyperthyroid cats. Conclusions and Clinical Importance: This validated HRQoL tool is useful to reliably quantify the influence of hyperthyroidism on the quality‐of‐life of affected cats and their owners. In the future, it could be considered of assistance in the clinical assessment of cats with hyperthyroidism. [ABSTRACT FROM AUTHOR]

Background: Accumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity. Methods: In this randomized, double-blind, placebo-controlled trial, we randomly assigned adults with obesity 1:1 (stratified by sex and obesity class) to receive intranasal oxytocin (24 IU) or placebo four times daily for 8 weeks. The primary end point was change in body weight (kg) from baseline to week 8. Key secondary end points included change in body composition (total fat mass [g], abdominal visceral adipose tissue [cm²], and liver fat fraction [proportion; range, 0 to 1; higher values indicate a higher proportion of fat]), and resting energy expenditure (kcal/day; adjusted for lean mass) from baseline to week 8 and caloric intake (kcal) at an experimental test meal from baseline to week 6. Results: Sixty-one participants (54% women; mean age ± standard deviation, 33.6 ± 6.2 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 36.9 ± 4.9) were randomly assigned. There was no difference in body weight change from baseline to week 8 between oxytocin and placebo groups (0.20 vs. 0.26 kg; P=0.934). Oxytocin (vs. placebo) was not associated with beneficial effects on body composition or resting energy expenditure from baseline to week 8 (total fat: difference [95% confidence interval], 196.0 g [-1036 to 1428]; visceral fat: 3.1 cm² [-11.0 to 17.2]; liver fat: -0.01 [-0.03 to 0.01]; resting energy expenditure: -64.0 kcal/day [-129.3 to 1.4]). Oxytocin compared with placebo was associated with reduced caloric intake at the test meal (-31.4 vs. 120.6 kcal; difference [95% confidence interval], -152.0 kcal [-302.3 to -1.7]). There were no serious adverse events. Incidence and severity of adverse events did not differ between groups. Conclusions: In this randomized, placebo-controlled trial in adults with obesity, intranasal oxytocin administered four times daily for 8 weeks did not reduce body weight. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT03043053.) [ABSTRACT FROM AUTHOR]

Gaucher disease (GD) is a lysosomal storage disease caused by glucocerebrosidase (GCase) enzyme deficiency. Gaucher cells transformed from the macrophages by progressive sphingolipid accumulation and infiltrate bone marrow, spleen, liver, and other organs. The accumulation of substrate causes inflammation, compromised cellular homeostasis, and disturbed autophagy. It has been hypothesized that this proinflammatory state of GD leads cytokines and chemokines release. As a result of inflammatory process, the cellular dysfunction caused by disruption of cellular signaling, organelle dysfunction, or autoimmune antibodies may affect endocrine profile of GD patients such as hormone levels, lipid profile, and bone mineral density status. A total of 13 patients confirmed to have GD, 12 non-neuronopathic type and one subacute neuronopathic type, were enrolled in our study. The median treatment duration in the enzyme therapy was 13.33 years (9–26 years). At least one endocrinological abnormality was detected in blood tests of nine patients. Hyperinsulinism was the most common finding although fasting blood glucose levels HgbA1c levels were normal in all patients. Two patients had osteopenia, and osteoporosis was detected in two patients. Low HDL levels were detected in six patients, but HDL levels below 23 mg/dL associated with disease severity have been detected in two patients who have not receiving enzyme replacement therapy. None of patients had thyroidal dysfunction. This study had revealed endocrinological abnormalities in GD patients that have not led any severe morbidity in our patients. However, thyroid hormone abnormalities, insulin resistance, or lipid profile abnormalities may cause unpredictable comorbidities. Endocrinological assessment in GD patients in routine follow-up may prevent possible clinical manifestation in long term as well as can define efficacy of ERT on endocrine abnormalities. [ABSTRACT FROM AUTHOR]

Context Gestational diabetes mellitus (GDM) is a complex obstetric condition affecting localized glucose metabolism, resulting in systemic metabolic dysfunction. Objective This cross-sectional study aimed to explore visceral adipose tissue (VAT) as an integral contributor to GDM, focusing on elucidating the specific contribution of obesity and GDM pathology to maternal outcomes. Methods Fifty-six nulliparous pregnant women were recruited, including normal glucose tolerant (NGT) (n = 30) and GDM (n = 26) participants. Participants were subgrouped as nonobese (BMI <30 kg/m2) or obese (BMI ≥30 kg/m2). Metabolic markers in circulation, VAT, and placenta were determined. Morphological analysis of VAT and immunoblotting of the insulin signaling cascade were performed. Results GDM participants demonstrated hyperinsulinemia and elevated homeostatic model assessment for insulin resistance (HOMA-IR) scores relative to NGT participants. The GDM-obese subgroup had significant VAT adipocyte hypoplasia relative to NGT-nonobese tissue. GDM-obese VAT had significantly lower insulin receptor substrate (IRS)-2 expression, with elevated ser312 phosphorylation of IRS-1, relative to NGT-nonobese. GDM-obese participants had significantly elevated circulating leptin levels and placental adipsin secretion, while GDM-nonobese participants had elevated circulating adipsin levels with reduced placental adiponectin secretion. Conclusion These findings suggest that GDM-obese pregnancy is specifically characterized by inadequate VAT remodeling and dysfunctional molecular signaling, which contribute to insulin resistance and hinder metabolic health. [ABSTRACT FROM AUTHOR]

Objective: To review the pharmacology of bexagliflozin in addition to its safety and efficacy from available clinical trials used for its approval, as well as available clinical evidence to date. Data Sources: A search of the National Institutes of Health Clinical Trials Registry (http://www.clinicaltrials.gov) and PubMed database was performed from inception through June 1, 2023. Study Selection and Data Extraction Quantification: The following study designs were included: meta-analyses, systematic review, clinical trial, or observational study design. Abstracts and drug monographs were also reviewed. Narrative or scoping reviews were excluded. Only articles in the English language and those evaluating the pharmacology, pharmacokinetics, safety, or efficacy of bexaglifozin in humans were included. Data Synthesis: Bexagliflozin reduces hemoglobin A1c ~0.5% with similar reductions in systolic blood pressure and body weight to other SGLT2 inhibitors. No cardiovascular outcomes trial is published, nor ongoing at this time. Adverse effects are similar to other SGLT2 inhibitors (genital mycotic and urinary tract infections, increased urination) including a warning for lower extremity amputation similar to canagliflozin. Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs: Although no cost-effectiveness data are available, statements from the manufacturer suggest a competitive price point. Given limited trial data, lower cost, if chosen, may create a temporary niche for bexagliflozin pending generic availability of other SGLT2 inhibitors. However, given lack of cardiovascular and renal outcome data, empagliflozin, dapagliflozin, or canagliflozin may be preferred. Conclusion: Bexagliflozin appears safe and effective as monotherapy and add-on pharmacological therapy for the treatment of T2D. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota studies in the field of endocrinology metabolism have attracted increasing attention in recent years. To comprehensively assess the evolving landscape of this research field, we conducted a thorough bibliometric analysis of gut microbiota studies in endocrinology metabolism indexed in the Web of Science database. Methods: We collected and analyzed 3,339 original research articles and reviews published from 1972 to 2023. Using various bibliometric indicators, we investigated publication trends, country contributions, international collaborations, prolific authors, top journals, and influential articles. Results: Our analysis revealed a significant upsurge in publications after 2010, indicating a growing scientific interest in microbiota and endocrinology metabolism. Keyword and thematic analyses have identified gut microbiota, obesity, diabetes, and inflammation as core research themes. Additionally, the roles of probiotics and prebiotics are increasingly researched for their therapeutic effects in shaping the microbiota. Conclusion: This study reveals that research in endocrinology metabolism is increasingly decoding the connection between gut microbiota and diseases. There’s also a growing focus on microbiota manipulation, which points to a shift towards personalized medicine. Future research should focus on integrating these findings into clinical practice, moving from lab-based studies to real-world patient care. [ABSTRACT FROM AUTHOR]

Objective: The bibliometric perspective examines publications using a quantitative way and statistics to analyze them. The purpose of the current study was to perform a comprehensive overview of the research on the pineal gland through bibliometric methods to determine the trends and rare topics related to the gland. Methods: The Web of Science database was used to identify the publications associated with the gland. The literature review exposed a total of 8719 publications. The identified publications were analyzed using the bibliometric approaches (VOSviewer Version 1.6.13). Results: The first studies on the pineal gland were in the 1970s. The most prolific country is the United States (2451). It was seen that most of the articles were published in Journal of Pineal Research. The majority of publications (97.09%) were written in English. The most prolific author is Reiter, Russel J. Moreover, the most prolific institute is the Centre National De La Recherche Scientifique (France). The most popular keywords in the articles were pineal gland, melatonin, circadian rhythm, rat, retina, photoperiod, circadian, aging, serotonin, oxidative stress, and brain. Conclusion: The results indicated the researchers’ interest in the gland and provided quantitative data about the place of the gland in the scientific area. Studies on this subject have tended to increase in recent years. As far as we know, this research is the first bibliometric study to provide a comprehensive analysis of scientific publications with an emphasis on the pineal gland since 1976. [ABSTRACT FROM AUTHOR]

Purpose: Osteoporosis is a metabolic bone disease characterized by decreased bone strength and mass, which predisposes patients to fractures and is associated with high morbidity and mortality. Like osteoporosis, obesity and diabetes are systemic metabolic diseases associated with modifiable risk factors and lifestyle, and their prevalence is increasing. They are related to decreased quality of life, functional loss and increased mortality, generating high costs for health systems and representing a worldwide public health problem. Growing evidence reinforces the role of bone marrow adipose tissue (BMAT) as an influential factor in the bone microenvironment and systemic metabolism. Given the impact of obesity and diabetes on metabolism and their possible effect on the bone microenvironment, changes in BMAT behavior may explain the risk of developing osteoporosis in the presence of these comorbidities. Methods: This study reviewed the scientific literature on the behavior of BMAT in pathological metabolic conditions, such as obesity and diabetes, and its potential involvement in the pathogenesis of bone fragility. Results: Published data strongly suggest a relationship between increased BMAT adiposity and the risk of bone fragility in the context of obesity and diabetes. Conclusion: By secreting a broad range of factors, BMAT modulates the bone microenvironment and metabolism, ultimately affecting skeletal health. A better understanding of the relationship between BMAT expansion and metabolic disturbances observed in diabetic and obese patients will help to identify regulatory pathways and new targets for the treatment of bone-related diseases, with BMAT as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: The study of thyroid status and its influence on neonatal and postneonatal development of newborns from mothers with endemic goiter (EG) is one of the topical areas of modern endocrinology. Objective: The study of thyroid hormone levels in newborns born to women with endemic goiter. Materials and Methods: The design of the study is based on a randomized controlled method, taking into account the requirements of CONSORT, with distribution into mutually comparable study groups. A study was carried out on 68 newborns born to women with EG. Methods included the collection of history and study of thyroid hormone levels in neonates and women in labor. Results: In newborns born from women with EG, thyroid‑stimulating hormone (TSH) in cord blood averaged 15.6 ± 0.87 mIU/l, which is 22.38% higher compared to the control group (P = 0.038). The difference between free triiodothyronine (T3) and thyroxine (T4) in newborns from mothers with EG in comparison to the control group was below 8.57% and 4.29%, respectively. In the 1st month of life, a lag in weight gain was noted by an average of 9.57% concerning practically healthy newborns. Conclusions: In newborns from women with EG, there was a decrease in T4 – 4.29% and T3 – 8.57%, against the background of an increase in the level of TSH to 22.38% in the cord blood relative to children from the control group. These fluctuations may persist in the 1st month of life and manifest as a delay in weight gain. [ABSTRACT FROM AUTHOR]

Background: Routine clinical coding of clinical outcomes in outpatient consultations still lags behind the coding of episodes of inpatient care. Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) offers an opportunity for standardised coding of key clinical information. Identifying the most commonly required SNOMED terms and grouping these into a reference set will aid future adoption in routine clinical care. Objective: To create a common endocrinology reference set to standardise the coding for outcomes of outpatient endocrine consultations, using a semi‐automated extraction of information from existing clinical correspondence. Methods: Retrospective review of data from an adult tertiary outpatient endocrine clinic between 2018 and 2019. A total of 1870 patients from postcodes within two regional areas of NHS Grampian (Aberdeen City and Aberdeenshire) attended the clinic. Following consultation, an automated script extracted each problem statement which was manually coded using the 'disorder' concepts from SNOMED CT (UK edition). Results: The review identified 298 relevant endocrine diagnoses, 99 findings and 142 procedures. There were a total of 88 (29.5%) commonly seen endocrine conditions (e.g., Graves' disease, anterior hypopituitarism and Addison's disease) and 210 (70.5%) less commonly seen endocrine conditions. Subsequently, consultant endocrinologists completed a survey regarding the common endocrine conditions; 28 conditions have 100% agreement, 25 have 90%–99% agreement, 31 have 50%–89% agreement and 4 have less than 59% agreement (which were excluded). Conclusion: Automated text parsing of structured endocrine correspondence allowed the creation of a SNOMED CT reference set for common endocrine disorders. This will facilitate funding and planning of service provision in endocrinology by allowing more accurate characterisation of the patient cohorts needing specialist endocrine care. [ABSTRACT FROM AUTHOR]

A mass spectrometry (LC‒MS/MS)-based interlaboratory comparison study was performed for nine steroid analytes with five participating laboratories. The sample set contained 40 pooled samples of human serum generated from preanalyzed leftovers. To obtain a well-balanced distribution across reference intervals of each steroid, the leftovers first underwent a targeted mixing step. All participants measured a sample set once using their own multianalyte protocols and calibrators. Four participants used in-house developed measurement platforms, including IVD-CE certified calibrators, which were used by three participants; the 5th lab used the whole LC‒MS kit from an IVD manufacturer. All labs reported results for 17-hydroxyprogesterone, androstenedione, cortisol, and testosterone, and four labs reported results for 11-deoxycortisol, corticosterone, cortisone, dehydroepiandrosterone sulfate (DHEAS), and progesterone. Good or acceptable overall comparability was found in Bland‒Altman and Passing‒Bablok analyses. Mean bias against the overall mean remained less than ±10 % except for DHEAS, androstenedione, and progesterone at one site and for cortisol and corticosterone at two sites (max. −18.9 % for androstenedione). The main analytical problems unraveled by this study included a bias not previously identified in proficiency testing, operator errors, non-supported matrix types and higher inaccuracy and imprecision at lower ends of measuring intervals. This study shows that intermethod comparison is essential for monitoring the validity of an assay and should serve as an example of how external quality assessment could work in addition to organized proficiency testing schemes. [ABSTRACT FROM AUTHOR]

Context: New animal welfare legislation and ethical guidelines encourage alternative approaches for canine contraception, instead of surgical gonadectomy which is considered invasive and unjustified in healthy dogs. Aims: Reversible contraception might be achieved by inhibition of aromatase (CYP19), an enzyme catalysing the conversion of androgens to oestrogens. This study provides insights into the spatio-temporal expression and distribution of aromatase in canine ovarian tissue. Methods: Ovarian tissue was collected from 39 healthy and sexually mature bitches during different stages of the oestrous cycle: pro-oestrus (n = 8), oestrus (n = 12), dioestrus (n = 9) (luteal phase) and anoestrus (n = 10). Localisation of cytochrome P450 aromatase was determined by immunohistochemistry. Key results: Aromatase activity in the dog is high during pro-oestrus, ovulation and early dioestrus. Comparing types of follicles and corpora lutea, the highest aromatase abundance was found in antral follicles and luteinising follicles, whereas corpora lutea and early antral follicles showed an intermediate presence of the enzyme. Interesting was the high abundance of aromatase in luteinising theca interna cells, prevailing over granulosa cells. Conclusions and implications: Understanding of cells involved in oestradiol production is important for targeted inhibition of oestradiol synthesis, possibly offering an approach for contraception and suppression of oestrus. In clinical practice, contraception in female dogs is traditionally achieved by surgical gonadectomy. As this method is discouraged by new animal welfare legislation in some parts of the world and is also related to several side effects, alternative possibilities for contraception are needed. Here, we report the distribution of aromatase in the canine ovary during different stages of the oestrous cycle. In-depth knowledge of oestrogen synthesis in the female dog is mandatory for targeted inhibition of oestradiol, possibly by the use of aromatase inhibitors. Photograph by M. P. Kowalewski. [ABSTRACT FROM AUTHOR]

Endocrinology is the study of hormones, endocrine glands and related diseases. Understanding basic hormonal physiology is essential for surgeons to manage patients with endocrine disorders. In this article we present the fundamental physiological mechanisms related to pituitary, thyroid, parathyroid and adrenal hormonal production, secretion and action. Moreover the methods used in the investigation for hormonal disturbances associated with these glands, resulting in excess or deficient secretion, are introduced. [ABSTRACT FROM AUTHOR]

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Hypoglycaemia in term infants is very common. Deciding on appropriate investigations and management is often challenging. The aims of this article are to help with understanding when, how and why to investigate symptoms of hypoglycaemia in full-term infants (born ≥37 weeks' gestational age). [ABSTRACT FROM AUTHOR]

Background: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic–solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli–Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. Conclusions: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening. [ABSTRACT FROM AUTHOR]

Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms generated by the concerted activity of these clocks is associated with metabolic disease. Here we tested the interactions between clocks in two critical components of organismal metabolism, liver and skeletal muscle, by rescuing clock function either in each organ separately or in both organs simultaneously in otherwise clock-less mice. Experiments showed that individual clocks are partially sufficient for tissue glucose metabolism, yet the connections between both tissue clocks coupled to daily feeding rhythms support systemic glucose tolerance. This synergy relies in part on local transcriptional control of the glucose machinery, feeding-responsive signals such as insulin, and metabolic cycles that connect the muscle and liver. We posit that spatiotemporal mechanisms of muscle and liver play an essential role in the maintenance of systemic glucose homeostasis and that disrupting this diurnal coordination can contribute to metabolic disease.

Hormones are indispensable for bone development, growth, and maintenance. While many of the genes associated with osteogenesis are well established, it is the recent findings in endocrinology that are advancing the fields of bone biology and toxicology. Endocrine-disrupting chemicals (EDCs) are defined as chemicals that interfere with the function of the endocrine system. Here, we report recent discoveries describing key hormone pathways involved in osteogenesis and the EDCs that alter these pathways. EDCs can lead to bone morphological changes via altering hormone receptors, signaling pathways, and gene expression. The objective of this review is to highlight the recent discoveries of the harmful effects of environmental toxicants on bone formation and the pathways impacted. Understanding the mechanisms of how EDCs interfere with bone formation contributes to providing a comprehensive toxicological profile of a chemical.

Adaptation of the islet β cell insulin-secretory response to changing insulin demand is critical for blood glucose homeostasis, yet the mechanisms underlying this adaptation are unknown. Here, we have shown that nutrient-stimulated histone acetylation plays a key role in adapting insulin secretion through regulation of genes involved in β cell nutrient sensing and metabolism. Nutrient regulation of the epigenome occurred at sites occupied by the chromatin-modifying enzyme lysine-specific demethylase 1 (Lsd1) in islets. β Cell-specific deletion of Lsd1 led to insulin hypersecretion, aberrant expression of nutrient-response genes, and histone hyperacetylation. Islets from mice adapted to chronically increased insulin demand exhibited shared epigenetic and transcriptional changes. Moreover, we found that genetic variants associated with type 2 diabetes were enriched at LSD1-bound sites in human islets, suggesting that interpretation of nutrient signals is genetically determined and clinically relevant. Overall, these studies revealed that adaptive insulin secretion involves Lsd1-mediated coupling of nutrient state to regulation of the islet epigenome.

Summary: Familial hypercholesterolemia (FH) is a genetic disorder that affects 1 in 300 people, leading to high cholesterol levels and significantly increased cardiovascular risk. The limitations of existing FH treatments underscore the need for innovative therapeutics, and gene therapy offers a promising alternative to address FH more effectively. In this review, we survey approved gene therapy drugs first and then delve into the landscape of gene addition, gene inactivation, and gene editing therapies for hypercholesterolemia, highlighting both approved interventions and those in various stages of development. We also discussed recent advancements in gene editing tools that are essential for their application in gene therapy. Safety considerations inherent to gene therapy are also discussed, emphasizing the importance of mitigating potential risks associated with such treatments. Overall, this review highlights the progress and prospects of gene therapies for FH treatments, underscoring their potential to revolutionize the management of this prevalent and challenging condition.

Summary: Endocrine glands secrete hormones into the circulation to target distant tissues and regulate their functions. The qualitative relationship between hormone-secreting organs and their target tissues is well established, but a quantitative approach is currently limited. Quantification is important, as it could allow us to study the endocrine system using engineering concepts of optimality and tradeoffs. In this study, we collected literature data on 24 human hormones secreted from dedicated endocrine cells. We find that the number of endocrine cells secreting a hormone is proportional to the number of its target cells. A single endocrine cell serves approximately 2,000 target cells, a relationship that spans 6 orders of magnitude of cell numbers. This suggests an economic principle of cells working near their maximal capacity, and glands that are no bigger than they need to be.

Summary: The immune system has emerged as an important target of thyroid hormones (THs); however, the role of TH in T cells has so far remained elusive. In this study, we assessed the effect of TH receptor α (TRα) signaling on activation and function of T cells. Our findings show that lack of canonical TRα action not only increased the frequency of regulatory T cells (Treg) but propelled an activated and migratory Treg phenotype and nuclear factor κB (NF-κB) activation in Treg. Conversely, canonical TRα action reduced activation of the NF-κB pathway previously shown to play a pivotal role in Treg differentiation and function. Taken together, our findings demonstrate that TRα impacts T cell differentiation and phenotype. Given the well-known interaction of inflammation, immune responses, and TH axis in e.g., severe illness, altered TH-TRα signaling may have an important role in regulating T cell responses during disease.

Summary: Chronic kidney disease (CKD) raises major concerns for global public health as it is characterized by high prevalence, low awareness, high healthcare costs, and poor prognosis. Therefore, our study prospectively established and validated native T1 mapping-based radiomics models for the prediction of renal fibrosis and renal function in patients with CKD. Moreover, the area under the receiver operating characteristic curve (AUC) and diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were used to evaluate its performance. Thus, our results show that radiomics based on native T1 mapping images can better identify renal function and renal fibrosis in patients with CKD and outperform conventional T1 mapping parameters of ΔT1 and T1%, thus providing more information for CKD management and clinical decision-making.

Summary: Continuous renal replacement therapy (CRRT) is a commonly utilized treatment modality for individuals experiencing severe acute kidney injury (AKI). The objective of this research was to construct and assess prognostic models for the timely discontinuation of CRRT in critically ill AKI patients receiving this intervention. Data were collected retrospectively from the MIMIC-IV database (n = 758) for model development and from the intensive care unit (ICU) of Huzhou Central Hospital (n = 320) for model validation. Nine machine learning models were developed by utilizing LASSO regression to select features. In the training set, all models demonstrated an AUROC exceeding 0.75. In the validation set, the XGBoost model exhibited the highest AUROC of 0.798, leading to its selection as the optimal model for the development of an online calculator for clinical applications. The XGBoost model demonstrates significant predictive capabilities in determining the discontinuation of CRRT.

Abstract Background Anti‐Müllerian hormone (AMH) holds potential as a biomarker for assessing the superovulation (SO) response in cattle. Nonetheless, there exists scant information regarding this aspect in the literature concerning dairy heifers. Given this gap, our objective is to explore the viability of AMH as an indicator for gauging the SO response specifically in Holstein heifers. Furthermore, our aim encompasses examining the variations in AMH levels within the same individuals before and after undergoing SO. Methods The study included 41 Holstein heifers. All heifers were superovulated and blood samples were taken both before and after the SO protocol. Results The findings revealed that the mean values of serum AMH concentrations before and after SO were 0.122 ng/mL (0.093–0.248 ng/mL) and 0.119 ng/mL (0.084–0.170 ng/mL), respectively. AMH concentrations in heifers were stratified into low (0.127 ng/mL) categories both before and after SO. Conclusions There was no significant correlation between AMH levels in the heifers both before and after SO treatment with the number of follicles, corpora lutea, total embryos collected or embryos transferred (p > 0.05). Furthermore, this study showed that serum AMH concentrations in Holstein heifers did not change after SO treatment. In this study, as AMH levels in Holstein heifers were in a narrow range, a relationship between AMH and SO response could not be determined. In future studies, we believe that it would be more useful to plan more studies in Holstein donor heifers, taking into account the number of animals and AMH levels.

A key goal of the field of endocrinology has been to understand the hormonal mechanisms that drive social behavior and influence reactions to others, such as oxytocin. However, it has sometimes been challenging to understand which aspects and influences of hormonal action are conserved and common among mammalian species, and which effects differ based on features of these species, such as social system. This challenge has been exacerbated by a focus on a relatively small number of traditional model species. In this review, we first demonstrate the benefits of using non-traditional models for the study of hormones, with a focus on oxytocin as a case study in adding species with diverse social systems. We then expand our discussion to explore differing effects of oxytocin (and its response to behavior) within a species, with a particular focus on relationship context and social environment among primate species. Finally, we suggest key areas for future exploration of oxytocin’s action centrally and peripherally, and how non-traditional models can be an important resource for understanding the breadth of oxytocin’s potential effects.

Summary: Patients with tuberous sclerosis complex (TSC) develop multi-organ disease manifestations, with kidney angiomyolipomas (AML) and cysts being one of the most common and deadly. Early and regular AML/cyst detection and monitoring are vital to lower TSC patient morbidity and mortality. However, the current standard of care involves imaging-based methods that are not designed for rapid screening, posing challenges for early detection. To identify potential diagnostic screening biomarkers of AML/cysts, we performed global untargeted metabolomics in blood samples from 283 kidney AML/cyst-positive or -negative TSC patients using mass spectrometry. We identified 7 highly sensitive chemical features, including octanoic acid, that predict kidney AML/cysts in TSC patients. Patients with elevated octanoic acid have lower levels of very long-chain fatty acids (VLCFAs), suggesting that dysregulated peroxisome activity leads to overproduction of octanoic acid via VLCFA oxidation. These data highlight AML/cysts blood biomarkers for TSC patients and offers valuable metabolic insights into the disease.

Summary: The role of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and triglyceride-glucose index (TyG index) in predicting all-cause and cause-specific mortalities remains elusive. This study included 384,420 adults from the Shanghai cohort and the UK Biobank (UKB) cohort. After multivariable adjustment in the Cox models, FPG ≥7.0 mmol/L or HbA1c ≥ 6.5% increased the risk of all-cause mortality, FPG ≥5.6 mmol/L or HbA1c ≥ 6.5% increased CVD-related mortality, and higher or lower TyG index increased all-cause and CVD-related mortalities in the Shanghai cohort; FPG ≥5.6 mmol/L, HbA1c ≥ 5.7%, TyG index

Summary: This comprehensive review delves into the significance of androgens in cervical cancer, examining both epidemiological evidence and the underlying biological mechanisms. Cervical cancer ranks as the fourth most prevalent cancer among women globally, with disproportionately higher incidence and mortality rates in less developed regions where cervical human papillomavirus (HPV) screening remains limited. Recent research highlights the previously underexplored role of androgens in cervical cancer. Notably, cervical tissues house androgen receptors, and elevated levels of endogenous androgens have been linked to an increased risk of cervical cancer. Androgens exert their influence on the development and progression of cervical cancer by impacting key cellular processes, including proliferation, apoptosis, differentiation, and epithelial cell transformation. Furthermore, specific HPV subtypes may interact with androgens, potentially modulating HPV-related cellular degeneration and transformation. In light of these findings, it is evident that androgens assume a crucial role in cervical cancer’s pathogenesis. Consequently, further investigations are warranted to deepen our understanding of the intricate relationship between androgens and cervical cancer. Such knowledge advancements can facilitate improved strategies for early prevention and treatment of cervical cancer, especially in regions with limited HPV screening access. This review underscores the importance of considering androgens as a vital component of the multifaceted landscape of cervical cancer etiology and progression, ultimately contributing to more effective clinical interventions.

This document is an editorial published in the journal Frontiers in Endocrinology. It discusses the role of environmental and internal factors in the neuroendocrine regulation of fish. The editorial highlights the importance of the brain-pituitary axis in controlling various physiological processes in fish, such as growth, reproduction, metabolism, and stress responses. It also mentions recent research findings on new components and mechanisms involved in endocrine regulation and plasticity in fish. The editorial introduces a research topic on neuroendocrine regulations in fish, which includes five original research articles covering different aspects of neuroendocrine regulation in fish. The articles explore the measurement of signaling molecules in fish tissues, the role of aromatases in zebrafish reproduction, the hormonal regulation of oocyte hydration in marine teleosts, the effects of cysteamine on growth and the GH/IGF axis in gilthead sea bream, and the role of somatostatin in regulating growth hormone secretion and reproductive hormone levels in tilapia. The editorial concludes by stating that the research topic provides valuable insights into the complex neuroendocrine mechanisms that regulate growth and reproduction in fish and hopes that it will contribute to the development of more effective strategies for promoting growth and reproductive success in fish populations. [Extracted from the article]

Dr. Gregory F. Ball has been awarded the 2024 Donald S. Farner Medal for Excellence in Research in the Field of Avian Endocrinology. The announcement was made at the International Symposium on Avian Endocrinology in April 2024. Dr. Ball, a professor at the University of Maryland, has made significant contributions to the study of hormones, brain, and behavior in birds. He has published over 350 papers and mentored numerous students and postdocs who have gone on to successful careers in academia. Dr. Ball's research has been funded by NIH and NSF grants, and he has received several prestigious awards throughout his career. [Extracted from the article]

Insulin antibody syndrome (IAS), also known as Hirata disease, is a rare condition characterized by spontaneous hypoglycemic episodes unrelated to exogenous insulin exposure. It is caused by elevated serum levels of insulin autoantibodies (IAA). IAS typically occurs when a triggering factor, such as medication or viral infection, interacts with a predisposing genetic background. Diagnosing IAS is challenging due to its rarity and the presence of multiple potential causes for hyperinsulinemic hypoglycemia. The presence of Whipple triad--symptoms of hypoglycemia, low plasma glucose concentration, and relief of symptoms after raising plasma glucose--strongly supports the diagnosis of IAS. However, the detection of IAA is considered the most reliable test. Timely diagnosis can facilitate appropriate treatment and prevent unnecessary imaging studies and invasive procedures, thereby reducing costs. Currently, no definitive guidelines exist for managing IAS. Most management strategies involve supportive measures due to the high rate of spontaneous remission, with hypoglycemia often managed through dietary interventions. However, a few medications have shown benefit. Although predominantly observed in the Japanese population, IAS cases have been reported in other ethnicities, including Caucasians. This report presents a unique case of IAS in an African American male. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is an autoimmune disease affecting genetically predisposed individuals that leads to chronic hyperglycemia. It is well established that the disease progresses through multiple phases that can extend over several years, from early risk development to clinical disease. The disease starts with presymptomatic islet autoimmunity (stage 1), marked by the presence of two or more islet autoantibodies; it progresses to stage 2, characterized by persistent autoantibodies and glucose abnormalities; and it culminates in stage 3, with clinical onset of hyperglycemia and declining beta-cell function. Novel interventions at each of these early stages have been attempted, with varying degrees of success as measured by delayed progression to stage 3 type 1 diabetes. [ABSTRACT FROM AUTHOR]

Short-chain fatty acids, including butyrate, have multiple metabolic benefits in individuals who are lean but not in individuals with metabolic syndrome, with the underlying mechanisms still being unclear. We aimed to investigate the role of gut microbiota in the induction of metabolic benefits of dietary butyrate. We performed antibiotic-induced microbiota depletion of the gut and fecal microbiota transplantation (FMT) in APOE*3-Leiden.CETP mice, a well-established translational model for developing human-like metabolic syndrome, and revealed that dietary butyrate reduced appetite and ameliorated high-fat diet-induced (HFD-induced) weight gain dependent on the presence of gut microbiota. FMT from butyrate-treated lean donor mice, but not butyrate-treated obese donor mice, into gut microbiota-depleted recipient mice reduced food intake, attenuated HFD-induced weight gain, and improved insulin resistance. 16S rRNA and metagenomic sequencing on cecal bacterial DNA of recipient mice implied that these effects were accompanied by the selective proliferation of Lachnospiraceae bacterium 28-4 in the gut as induced by butyrate. Collectively, our findings reveal a crucial role of gut microbiota in the beneficial metabolic effects of dietary butyrate as strongly associated with the abundance of Lachnospiraceae bacterium 28-4.