Obesity Conditions Research Articles

Mental Health Implications of Weight Loss Medications: A Narrative Review

Obesity and mental illness are commonly encountered clinical issues that nurse practitioners manage. A bidirectional and complex relationship exists between these 2 clinical concerns, with management of either condition affecting the other. Individuals with obesity and/or mental illness experience disparities in health outcomes. Even among individuals without mental health conditions, pharmacologic management of obesity can have mental health adverse effects. This review discusses current weight loss medications and their mental health implications. Nurse practitioners caring for individuals with obesity and/or mental health conditions can benefit from considering the effect of each medication on physical and mental health outcomes.

Association of relative handgrip strength on the development of diabetes mellitus in elderly Koreans.

Diabetes mellitus (DM) is a significant public health concern, particularly in the elderly population. Absolute handgrip strength (HGS) serves to quantify muscle strength. It is recommended that the risk of low muscle strength and increased body mass index be concurrently evaluated using relative HGS. There are currently insufficient evidence regarding the relationship between relative HGS and DM in the elderly Korean population. Therefore, the association between relative HGS and the development of DM in Korean elderly was investigated. Data from the Korean Longitudinal Study of Ageing were used to determine the odds ratio (OR) between relative HGS and DM during the follow-up period from 2006-2020 among Korean men and women aged ≥65 years without DM when they first participated in this survey. Analysis was conducted using the Generalized Estimating Equation method. Trend analysis was performed for DM development based on relative HGS. Among elderly males, higher relative HGS groups had reduced odds of developing DM (Middle tertile: OR 0.87, 95% CI 0.61-1.23, p = 0.419.) (Upper tertile: OR 0.82, 95% CI 0.56-1.18, p = 0.281.) Among elderly females, the reductions were similar. (Middle tertile: OR 0.82, 95% CI 0.66-1.03, p = 0.087.) (Upper tertile: OR 0.79, 95% CI 0.50-1.25, p = 0.306.) However, these differences were not statistically significant. Significant predictors of new-onset DM included age, BMI (overweight/obese), household income, alcohol consumption, hypertension, and chronic liver disease. Trend tests indicated a substantial decrease in the OR as the relative HGS increased for male and total groups (p for trend < 0.05). Relative HGS did not achieve statistical significance. Our findings indicate that BMI, particularly overweight and obesity, significantly predicts new-onset DM. However, trend tests indicated a substantial decrease in the OR as the relative HGS increased for male and total groups (p for trend < 0.05), even after adjusting for BMI categories. Despite the lack of statistical significance in some cases, the trend suggests that promoting resistance exercises to enhance HGS could be beneficial in DM prevention. Comprehensive DM prevention strategies should include managing obesity and chronic conditions for elderly.

Improvement in Symptoms of Depression and Anxiety and Cardiometabolic Risk Factors in Children and Adolescents with Overweight and Obesity Following the Implementation of a Multidisciplinary Personalized Lifestyle Intervention Program

Background/Objectives: Childhood obesity is one of the most challenging contemporary public health problems. Children and adolescents with obesity experience multiple psychosocial difficulties, such as low self-esteem, depression, anxiety, and behavioral problems, which persist for a long time. The aim of the study was to assess the effect of a multidisciplinary personalized lifestyle intervention for depressive and anxiety symptoms, as evaluated by psychometric questionnaires, and their effect and association with cardiometabolic parameters in children and adolescents with overweight and obesity conditions before and after the intervention. Methods: Six hundred and eleven (n = 611) children and adolescents (mean age ± SE: 10.39 ± 0.10 years; 51.5% females, 46.6% pubertal) were studied prospectively. Subjects were classified as being obese (50.2%), overweight (33.5%), or having a normal BMI (16.2%) according to IOTF criteria. All participants entered a 1-year lifestyle intervention program; laboratory investigations were obtained at the beginning and end of the study and two psychometric questionnaires were completed, the CDI and SCARED, which evaluate symptoms of depression and anxiety, respectively. Results: Following the lifestyle intervention, a significant decrease was noted in anxiety scores in all subjects and in depression scores in youth with obesity, as well as in adolescents with obesity, while females presented a reduced response to the intervention. Insulin resistance and metabolic syndrome parameters, cortisol, PRL, and LH concentrations were positive predictors for depressive and anxiety symptoms. Conclusions: The implementation of a multidisciplinary personalized lifestyle intervention program in the management of childhood obesity is associated with a significant decrease in cardiometabolic and psychosocial comorbidities in children with and without excess adiposity. The improvement in mental health is speculated to be mediated by an improvement in energy metabolism with subsequent improvement in neuroinflammation owing to lifestyle changes.

Analysis of ventricular repolarization parameters and heart rate variability in obesity: a comparative study

Obesity is associated with dysfunctional electrocardiographic and cardiac autonomic parameters, which may lead to increased cardiovascular morbidity. Novel electrocardiographic repolarization markers such as Tpeak-Tend (Tpe) interval have not yet been deeply studied in obese patients. We aimed to investigate the association between ventricular repolarization parameters and heart rate variability (HRV) and how they are affected by changes occurring in the cardiac autonomic nervous system. Ninety subjects categorized by Southeast Asian BMI (kg/m2) standards - normal (18-22.9), overweight (23-24.9), and obese (> 24.9), underwent assessment of ventricular repolarization parameters and HRV. Linear correlation between different parameters was also conducted. Obese subjects exhibited longer QTc and Tpe intervals compared to normal-weight subjects (p-value < 0.001, 0.026 respectively). The QTc interval showed a significant correlation (p < 0.05) with all HRV parameters by linear correlation, while the Tpe interval did not. Anthropometric parameters (BMI, WC, and WHR) were also correlated to both ventricular repolarization variables and HRV. While changes in the QTc interval may be due to obesity and/or autonomic changes occurring in the obese state, the Tpe interval does not show a relation with autonomic parameters. Thus, implicating that a change in the Tpe interval is primarily due to the direct effect of either cardiac or visceral obesity. The observed associations between ECG parameters, obesity indices, and HRV parameters suggest a role for ECG in screening for cardiovascular morbidity.

Significance of LIF/LIFR Signaling in the Progression of Obesity-Driven Triple-Negative Breast Cancer

American women with obesity have an increased incidence of triple-negative breast cancer (TNBC). The impact of obesity conditions on the tumor microenvironment is suspected to accelerate TNBC progression; however, the specific mechanism(s) remains elusive. This study explores the hypothesis that obesity upregulates leukemia inhibitory factor receptor (LIFR) oncogenic signaling in TNBC and assesses the efficacy of LIFR inhibition with EC359 in blocking TNBC progression. TNBC cell lines were co-cultured with human primary adipocytes, or adipocyte-conditioned medium, and treated with EC359. The effects of adiposity were measured using cell viability, colony formation, and invasion assays. Mechanistic studies utilized RNA-Seq, Western blotting, RT-qPCR, and reporter gene assays. The therapeutic potential of EC359 was tested using xenograft and patient-derived organoid (PDO) models. The results showed that adipose conditions increased TNBC cell proliferation and invasion, and these effects correlated with enhanced LIFR signaling. Accordingly, EC359 treatment reduced cell viability, colony formation, and invasion under adipose conditions and blocked adipose-mediated organoid growth and TNBC xenograft tumor growth. RNA-Seq analysis identified critical pathways modulated by LIF/LIFR signaling in diet-induced obesity mouse models. These findings suggest that adiposity contributes to TNBC progression via the activation of the LIF/LIFR pathway, and LIFR inhibition with EC359 represents a promising therapeutic approach for obesity-associated TNBC.

Bergamot (Citrus bergamia), a (Poly)Phenol-Rich Source for Improving Osteosarcopenic Obesity: A Systematic Review

This systematic review investigates the potential of bergamot, a polyphenol-rich citrus fruit, in improving osteosarcopenic obesity, a condition characterized by the simultaneous presence of osteoporosis, obesity, and sarcopenia. Bergamot extracts have been suggested to possess several pharmacological properties, including anti-inflammatory and antioxidant effects, which could be useful in the management of age-related diseases and neuromuscular health. The review highlights the promising effects of bergamot extracts on skeletal muscle mass and function, particularly in the context of obesity, metabolic syndrome, osteosarcopenic obesity, and osteoporosis. Furthermore, some studies have shown that bergamot extracts can improve the metabolic balance, endothelial function, and maximal oxygen uptake in athletes, highlighting their potential benefits for skeletal muscle health. Taken together, these results suggest that bergamot extracts, especially those rich in polyphenols, may be a valuable adjunct in the management of osteosarcopenic obesity and other associated clinical conditions involving pro-inflammatory effects on organs and tissues.

Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.

Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential for maintaining physiological functions and metabolic homeostasis. However, chronic elevation of BCAAs causes metabolic diseases such as obesity, type 2 diabetes (T2D), and metabolic-associated fatty liver disease (MAFLD). Adipose tissue, skeletal muscle, and the liver are the three major metabolic tissues not only responsible for controlling glucose, lipid, and energy balance but also for maintaining BCAA homeostasis. Under obese and diabetic conditions, different pathogenic factors like pro-inflammatory cytokines, lipotoxicity, and reduction of adiponectin and peroxisome proliferator-activated receptors γ (PPARγ) disrupt BCAA metabolism, leading to excessive accumulation of BCAAs and their downstream metabolites in metabolic tissues and circulation. Mechanistically, BCAAs and/or their downstream metabolites, such as branched-chain ketoacids (BCKAs) and 3-hydroxyisobutyrate (3-HIB), impair insulin signaling, inhibit adipogenesis, induce inflammatory responses, and cause lipotoxicity in the metabolic tissues, resulting in multiple metabolic disorders. In this review, we summarize the latest studies on the metabolic regulation of BCAA homeostasis by the three major metabolic tissues-adipose tissue, skeletal muscle, and liver-and how dysregulated BCAA metabolism affects glucose, lipid, and energy balance in these active metabolic tissues. We also summarize therapeutic approaches to restore normal BCAA metabolism as a treatment for metabolic diseases.

Questioning the status quo: Latino community members as researchers in the study of health equity.

Latinos experience disproportionate rates of obesity and related conditions like type 2 diabetes, which are projected to increase (Mohebi et al., 2022). Standard interventions for these issues often fall short due to individual-focused approaches and the lack of culturally sensitive definitions of health that include emotional, physical, political, and social domains (Gutierrez Chavez et al., 2022; Ritchie et al., 2020). Multilevel and multidimensional research efforts, integrating social justice-informed orientations, psychotherapy science, and behavioral medicine, are crucial for addressing these health inequities (Asnaani, 2023; Collins et al., 2018; Rodriguez Espinosa & Verney, 2021). Additionally, critically analyzing researcher and participant roles is essential to avoid perpetuating systemic racism (Cook et al., 2023). This article highlights the need for a paradigm shift in psychotherapy research by (a) describing Latino families' eating patterns and coping strategies for emotional distress through focus groups in the community and (b) illustrating the process behind the community-partnered development of a culturally responsive mindfulness-based health intervention. Importantly, this research approach emphasizes liberation psychology theory in the exploration of structural influences affecting health (Martín-Baró, 1996). While mindfulness techniques are feasible in this population (Cotter & Jones, 2020), Latino communities may not be amenable to the current presentation of mainstream psychological science interventions. Our research paradigm informed the conceptualization of mindfulness techniques through both clinical science and critical lenses. Thus, this study argues for reconceptualizing the definition of a successful psychotherapy study to include community engagement and liberatory principles, making the potential for big needle jumps in addressing health inequities incalculable. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

SICOB Italian clinical practice guidelines for the surgical treatment of obesity and associated diseases using GRADE methodology on bariatric and metabolic surgery.

Obesity is a chronic disease associated with increased morbidity and mortality and reduced quality of life. Pharmacotherapy can be associated with life style changes in increasing and maintaining weight loss and ameliorating obesity-related complications and comorbidities. In patients affected by obesity and uncontrolled obesity-associated complications or high degrees of BMI (> 40 Kg/m2), metabolic bariatric surgery can be a valid therapeutic option. Many different types of surgical procedures have been developed in last decades, mainly performed via laparoscopic approaches. However, clinical indications for metabolic and bariatric surgery (MBS) and the choice of the most appropriate type of procedure have not been clarified so far.The Italian Society of Bariatric and Metabolic Surgery for Obesity (Società Italiana di Chirurgia dell'Obesità e delle Malattie Metaboliche-SICOB) decided to design and develop the updated version of the Italian guidelines aimed at assisting healthcare professionals in the choice of the surgical option for the treatment of obesity and related conditions. Between June and October 2022, a panel of 24 experts and an evidence review team (ERT, 10 members), participated in the definition of clinical questions, outcomes, and recommendations and collected and analyzed all the available evidence on the basis of pre-specified search strategies. GRADE methodology and PICO (Patient, Intervention, Comparison, Outcome) conceptual framework have been adopted for the development of the present guidelines. Aim of the present guideline is to verify indications to surgery with respect to the presence of comorbid conditions, evaluate the different types of surgical approaches and endoscopic bariatric procedure and revise indication to revision surgery and postoperative procedures.

Molecular and Cellular Neurobiology of Spreading Depolarization/Depression and Migraine: A Narrative Review.

Migraine is a prevalent neurological disorder, particularly among individuals aged 20-50 years, with significant social and economic impacts. Despite its high prevalence, the pathogenesis of migraine remains unclear. In this review, we provide a comprehensive overview of cortical spreading depolarization/depression (CSD) and its close association with migraine aura, focusing on its role in understanding migraine pathogenesis and therapeutic interventions. We discuss historical studies that have demonstrated the role of CSD in the visual phenomenon of migraine aura, along with modern imaging techniques confirming its propagation across the occipital cortex. Animal studies are examined to indicate that CSD is not exclusive to migraines; it also occurs in other neurological conditions. At the cellular level, we review how CSD is characterized by ionic changes and excitotoxicity, leading to neuronal and glial responses. We explore how CSD activates the trigeminal nervous system and upregulates the expression of calcitonin gene-related peptides (CGRP), thereby contributing to migraine pain. Factors such as genetics, obesity, and environmental conditions that influence the CSD threshold are discussed, suggesting potential therapeutic targets. Current treatments for migraine, including prophylactic agents and CGRP-targeting drugs, are evaluated in the context of their expected effects on suppressing CSD activity. Additionally, we highlight emerging therapies such as intranasal insulin-like growth factor 1 and vagus nerve stimulation, which have shown promise in reducing CSD susceptibility and frequency. By elucidating the molecular and cellular mechanisms of CSD, this review aims to enhance the understanding of migraine pathogenesis and support the development of targeted therapeutic strategies.

Roles of thyroid and leptin hormones and their crosstalk in male reproductive functions: an updated review.

This review aims to provide updated information regarding the role of thyroid and leptin hormones and their crosstalk in affecting the male reproductive function in hypothyroid and obesity conditions. A wide literature search was made using online search engines on published articles using keywords including thyroid hormone, hypothyroidism, leptin hormone, hyperleptinemia, obesity, the relationship between thyroid and leptin hormones and male reproduction, and hypothyroidism, obesity, and male reproduction. All information pertaining thyroid and leptin hormone effects on male reproduction, hypothyroidism, hyperleptinemia, and obesity effect on male fertility as well as the related molecular mechanisms are obtained. Thyroid and leptin hormones individually play a significant role in male reproduction. Alterations of these hormones' levels could adversely affect the male reproductive functions. PI3K/AKT signaling was found to be the major signaling pathway involved in mediating the effect of both hormones on male reproduction. Impaired crosstalk between the two hormones may occur in hypothyroidism with obesity which would contribute towards male reproductive dysfunction.

Amphiregulin Upregulation in Visfatin-Stimulated Colorectal Cancer Cells Reduces Sensitivity to 5-Fluororacil Cytotoxicity.

Colorectal cancer (CRC) has become a prevalent and deadly malignancy over the years. Drug resistance remains a major challenge in CRC treatment, significantly affecting patient survival rates. Obesity is a key risk factor for CRC development, and accumulating evidence indicates that increased secretion of adipokines, including Visfatin, under obese conditions contributes to the development of resistance in CRC to various therapeutic methods. Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family, which activates the EGF receptor (EGFR), influencing multiple tumorigenic characteristics of cancers. Abnormal expression levels of AREG in cancer cells have been associated with resistance to anti-EGFR therapy in patients. However, it remains unclear whether this abnormal expression also impacts CRC resistance to other chemotherapeutic drugs. The aim of this study is to examine whether AREG expression levels could be affected in CRC cells under Visfatin stimulation, thereby initiating the development of resistance to 5-fluororacil (5-FU). Through our results, we found that Visfatin indeed increases AREG expression, reducing the sensitivity of HCT-116 CRC cells to 5-FU cytotoxicity. Moreover, AREG upregulation is regulated by STAT3-CREB transcription factors activated by JNK1/2 and p38 signaling. This study highlights the significant role of AREG upregulation in CRC cells in initiating chemotherapeutic resistance to 5-FU under Visfatin stimulation. These findings provide a deeper understanding of drug resistance development in CRC under obese conditions and offer new insights into the correlation between an abnormal increase in AREG levels and the development of 5-FU-resistance in CRC cells, which should be considered in future clinical applications.

Carbocyclic setmelanotide analogs maintain biochemical potency at melanocortin 4 receptors.

The melanocortin 4 receptor (MC4R) plays a critical role in satiety and energy homeostasis, and its dysregulation is implicated in numerous hyperphagic and obese disease states. Setmelanotide, a disulfide-based cyclic peptide, can rescue MC4R activity and treat obesities caused by genetic defects in MC4R signaling. But this peptide has moderate blood-brain barrier penetrance and metabolic stability, which can limit its efficacy in practice. Based on the cryo-electron microscopy structure of setmelanotide-bound MC4R, we hypothesized that replacing its lone disulfide bond with more metabolically stable and permeability-enhancing carbon-based linker groups could improve pharmacokinetic properties without abolishing activity. To test this, we used chemistry developed by our lab to prepare 11 carbocyclic (alkyl, aryl, perfluoroalkyl, and ethereal) analogs of setmelanotide and determined their biochemical potencies at MC4R in vitro. Ten analogs displayed full agonism, showing that disulfide replacement is tolerant of linkers ranging in size, rigidity, and functional groups, with heteroatom- or aryl-rich linkers displaying superior potencies.

Multifactorial analysis of risk factors for foot ulcers in patients with neurovascular complications of diabetes.

Diabetic foot ulcers (DFU) are a major complication associated with significant morbidity and mortality. While numerous studies have investigated risk factors for these ulcers in general, few have focused specifically on patients with Neurovascular Complications of Diabetes. This study aimed to evaluate the prevalence and risk factors for DFU in this specific population. We analyzed data from the National Institutes of Health (NIS) database for the years 2017-2019, involving a cohort of 161,834 patients aged over 18 who were diagnosed with neurovascular complications of diabetes. Demographic characteristics (age, gender, ethnicity), hospital characteristics, comorbidities, and other relevant data were included for analysis. A binary logistic regression model was generated to identify independent risk factors for DFU. The prevalence of DFU among patients with neurovascular complications of diabetes was 29.4% during the period from 2017 to 2019. Compared to patients without DFU, those with DFU had longer hospitalization times and higher costs. The multiple regression analysis revealed that Iron-deficiency anemia (OR, 1.10; 95% CI, 1.01-1.11; P=0.019), Hypertension (OR, 1.07; 95% CI, 1.03-1.11; P=0.001), Obesity (OR, 1.08; 95% CI, 1.06-1.11; P<0.001), Peripheral vascular disorders (PVD) (OR, 1.69; 95% CI, 1.65-1.74; P<0.001), Osteomyelitis (OR, 7.10; 95% CI, 6.89-7.31; P<0.001), Tinea pedis (OR, 1.89; 95% CI, 1.59-2.26; P<0.001), Sepsis (OR, 1.24; 95% CI, 1.20-1.28; P<0.001), and onychomycosis (OR, 1.26; 95% CI, 1.13-1.42; P<0.001) were independent predictors for DFU in this population. The study found a high prevalence of DFU in patients with neurovascular complications of diabetes. Identifying and addressing risk factors such as deficiency anemia, hypertension, obesity, PVD, infections, and foot conditions may contribute to reducing the prevalence of DFU in this vulnerable population.

A machine learning classifier-based approach for diabetes mellitus risk prediction.

Currently, Diabetes Mellitus (DM) can be life-threatening due to the dietary habits and lifestyle choices of individuals. Diabetes is characterised by elevated levels of glucose in the blood and an excess of protein in the blood. Poor eating habits and lifestyles are largely responsible for the rise in overweight, obesity, and various related conditions. This study investigated many diabetes-related risk forecasting techniques and algorithms. The eight machine learning (ML) algorithms used the diabetes dataset to test various prediction techniques, including a Support Vector Classifier, gradient-boosting, multilayer perceptron, random forest, K-nearest neighbors, logistic regression, extreme gradient boosting, and decision tree. To enhance the diabetic prediction ability of the model, we suggested using Feature Engineering (FE) and feature scaling. For our investigation, we utilized the Mendeley dataset on diabetes to assess the capacity of the model to predict diabetes. We developed a model by using Python programming and eight classification techniques. The Random Forest with 99.21%, Gradient Boosting with 99.61%, Extreme Gradient Boosting, and Decision Tree achieved the highest F1 score (99.81%), accuracy rate (99.80%), precision (99.81%), and recall (99.81%) of all classification approaches.

8568 Prevalence of Raised Blood Pressure in Individuals With 46,XY DSD: an I-DSD Registry study

Abstract Disclosure: A.K. Lucas-Herald: None. J. Bryce: None. M. Chen: None. C. Naotunna: None. M. Sepich: None. L. Tack: None. M. Cools: None. S. Poyrazoglu: None. E. Globa: None. M. Stancampiano: None. H.L. Claahsen-van der Grinten: None. T. Guran: None. Z. Yavas Abali: None. L. de Vries: None. S.E. Hannema: None. A. Guven: None. D. Janus: None. H.A. AlShaikh: None. L. Guazzarotti: None. G. Herrmann: None. U. Probst: None. N. Lenherr-Taube: None. D. Konrad: None. M.W. O’Reilly: None. M. Steigert: None. A. Ucar: None. M. Wasniewska: None. R. Coco: None. P. Holterhus: None. V.M. Schwitzgebel: None. S.F. Ahmed: None. Introduction: Males with XY Differences of Sex Development (DSD) may have an increased risk of high blood pressure and accelerated vascular ageing. It is not clear which individuals are most at risk of this. Methods: Data were obtained from centres using the International Disorders of Sex Development (I-DSD) Registry on boys and men with 46,XY DSD. Blood pressure (BP) readings were requested as well as information on risk factors for hypertension (birthweight, obesity, family history, associated malformations) as well as ongoing management of any high BP readings. Results: In total BP readings from 208 individuals with 46,XY DSD were available from 22 centres worldwide. Of these, the median (range) age at the time of the BP reading was 13 years (1, 54). In total 97 (47%) had a non-specific XY DSD; 37 (18%) had a disorder of gonadal development; 34 (16%) had a disorder of androgen synthesis; 23 (11%) had a disorder of androgen action; 14 (7%) had hypogonadotrophic hypogonadism; and 3 (1%) had a disorder of Müllerian development. There were 77 (37%) cases ≥16 years of age, of whom 7 (10%) were classified as hypertensive. The median systolic BP of those adults with an underlying DSD was 120 mmHg (90, 153). Of the 131 (63%) individuals &amp;lt;16 years of age, 25 (19%) had a BP &amp;gt; 95th centile for age and height. The median BP standard deviation score (SDS) of those children with an underlying DSD was 0.3 (-2, 3). Of the 25 children with a raised BP, 6 (24%) had a BP &amp;gt;99.8th centile and 19 (76%) had a BP &amp;gt;98th centile. Boys with disorders of gonadal development had the highest median BP SDS at 0.9, although this was not significantly different to any other condition. There were no differences in BP SDS at the time of the study according to gestation at birth, birthweight, type of underlying of condition or presence of obesity or a co-existing anomaly however BP SDS was significantly associated with age. Of the 32 with hypertension, 3 (9%) were treated with antihypertensives; 2 (6%) had an echocardiogram and none (0%) are reported to have had ambulatory blood pressure monitoring. Conclusions: Up to 20% of young people with XY DSD have a BP in the hypertensive range during childhood at clinic compared to approximately 5% reported global prevalence in children. Our findings suggest that routine BP measurements should be recommended in this group as well as investigation to determine whether this is true hypertension or secondary to clinic anxiety. Management of these individuals requires adherence to international guidelines to prevent future cardiovascular damage. More research into the underlying cause of this phenomenon is required. Presentation: 6/1/2024

8568 Prevalence of Raised Blood Pressure in Individuals With 46,XY DSD: an I-DSD Registry study

Abstract Disclosure: A.K. Lucas-Herald: None. J. Bryce: None. M. Chen: None. C. Naotunna: None. M. Sepich: None. L. Tack: None. M. Cools: None. S. Poyrazoglu: None. E. Globa: None. M. Stancampiano: None. H.L. Claahsen-van der Grinten: None. T. Guran: None. Z. Yavas Abali: None. L. de Vries: None. S.E. Hannema: None. A. Guven: None. D. Janus: None. H.A. AlShaikh: None. L. Guazzarotti: None. G. Herrmann: None. U. Probst: None. N. Lenherr-Taube: None. D. Konrad: None. M.W. O’Reilly: None. M. Steigert: None. A. Ucar: None. M. Wasniewska: None. R. Coco: None. P. Holterhus: None. V.M. Schwitzgebel: None. S.F. Ahmed: None. Introduction: Males with XY Differences of Sex Development (DSD) may have an increased risk of high blood pressure and accelerated vascular ageing. It is not clear which individuals are most at risk of this. Methods: Data were obtained from centres using the International Disorders of Sex Development (I-DSD) Registry on boys and men with 46,XY DSD. Blood pressure (BP) readings were requested as well as information on risk factors for hypertension (birthweight, obesity, family history, associated malformations) as well as ongoing management of any high BP readings. Results: In total BP readings from 208 individuals with 46,XY DSD were available from 22 centres worldwide. Of these, the median (range) age at the time of the BP reading was 13 years (1, 54). In total 97 (47%) had a non-specific XY DSD; 37 (18%) had a disorder of gonadal development; 34 (16%) had a disorder of androgen synthesis; 23 (11%) had a disorder of androgen action; 14 (7%) had hypogonadotrophic hypogonadism; and 3 (1%) had a disorder of Müllerian development. There were 77 (37%) cases ≥16 years of age, of whom 7 (10%) were classified as hypertensive. The median systolic BP of those adults with an underlying DSD was 120 mmHg (90, 153). Of the 131 (63%) individuals &amp;lt;16 years of age, 25 (19%) had a BP &amp;gt; 95th centile for age and height. The median BP standard deviation score (SDS) of those children with an underlying DSD was 0.3 (-2, 3). Of the 25 children with a raised BP, 6 (24%) had a BP &amp;gt;99.8th centile and 19 (76%) had a BP &amp;gt;98th centile. Boys with disorders of gonadal development had the highest median BP SDS at 0.9, although this was not significantly different to any other condition. There were no differences in BP SDS at the time of the study according to gestation at birth, birthweight, type of underlying of condition or presence of obesity or a co-existing anomaly however BP SDS was significantly associated with age. Of the 32 with hypertension, 3 (9%) were treated with antihypertensives; 2 (6%) had an echocardiogram and none (0%) are reported to have had ambulatory blood pressure monitoring. Conclusions: Up to 20% of young people with XY DSD have a BP in the hypertensive range during childhood at clinic compared to approximately 5% reported global prevalence in children. Our findings suggest that routine BP measurements should be recommended in this group as well as investigation to determine whether this is true hypertension or secondary to clinic anxiety. Management of these individuals requires adherence to international guidelines to prevent future cardiovascular damage. More research into the underlying cause of this phenomenon is required. Presentation: 6/1/2024

Luteolin alleviates muscle atrophy, mitochondrial dysfunction and abnormal FNDC5 expression in high fat diet-induced obese rats and palmitic acid-treated C2C12 myotubes

Obesity is associated with a series of skeletal muscle impairments and dysfunctions, which are characterized by metabolic disturbances and muscle atrophy. Luteolin is a phenolic phytochemical with broad pharmacological activities. The present study aimed to evaluate the protective effects of Luteolin on muscle function and explore the potential mechanisms in high-fat diet (HFD)-induced obese rats and palmitic acid (PA)-treated C2C12 myotubes. Male Sprague-Dawley (SD) rats were fed with a control diet or HFD and orally administrated 0.5% sodium carboxymethyl cellulose (vehicle) or Luteolin (25, 50 and 100 mg/kg, respectively) for 12 weeks. The results showed that Luteolin ameliorated HFD-induced body weight gain, glucose intolerance and hyperlipidemia. Luteolin also alleviated muscle atrophy, decreased ectopic lipid deposition and prompted muscle-fiber-type conversion in the skeletal muscle. Meanwhile, we observed an evident improvement in mitochondrial quality control and respiratory capacity, accompanied by reduced oxidative stress. Mechanistic studies indicated that AMPK/SIRT1/PGC-1α signaling pathway plays a key role in the protective effects of Luteolin on skeletal muscle in the obese states, which was further verified by using specific inhibitors of AMPK and SIRT1. Moreover, the mRNA expression levels of markers in brown adipocyte formation were significantly up-regulated post Luteolin supplementation in different adipose depots. Taken together, these results revealed that Luteolin supplementation might be a promising strategy to prevent obesity-induced loss of mass and biological dysfunctions of skeletal muscle.

Preferential inhibition of α-amylase by cinnamaldehyde-based hydrazones: A comparative study

The escalating issue of obesity and related health conditions, including diabetes mellitus and coronary heart disease, necessitates the development of digestive enzyme inhibitors. Targeting pancreatic lipase to inhibit fatty acid generation to attain reduced lipid absorption is a promising approach for identifying effective agents. Orlistat, the only clinically approved pancreatic lipase inhibitor, is associated with gastrointestinal side effects like oily stools, spotting, and flatulence. Concurrently, α-amylase inhibitors can mitigate rapid spikes in blood sugar levels. With the growing significance of natural products in pharmaceutical research, cinnamaldehyde has been recognized as a potential enzyme inhibitor. This study explores the effects of cinnamaldehyde-derived hydrazone Schiff bases on lipase and α-amylase through in vitro experiments. The synthesized compounds exhibited IC50 value for lipase in the same range ((0.41–12.58) × 10−8 M) as exhibited by the commercial drug orlistat (5.76 × 10−8 M). However, for α-amylase inhibition, the compounds (IC50 value = 0.37–9.54 × 10−9 M) were found effective inhibitors of acarbose (IC50 value = 6.76 × 10−6 M) and curcumin (IC50 value = 467 × 10−9 M). In silico DFT studies, molecular docking, drug likeliness, bioactivity score, ADME, and toxicity are also investigated for these compounds.

Effect of Obesity and Metabolic Health Status on Metabolic-Associated Steatotic Liver Disease among Renal Transplant Recipients Using Hepatic Steatosis Index

Background/Objectives: Obesity and metabolic conditions increase the risk of metabolic-associated steatotic liver disease (MASLD). This study examined the risk of MASLD in 137 renal transplant recipients (RTRs) from a single-center hospital on the basis of their obesity and metabolic health status. Methods: Participants were categorized into four groups: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically abnormal nonobese (MANO), and metabolically abnormal obese (MAO). MASLD was assessed using the hepatic steatosis index (HSI), calculated as 8 × (aspartate aminotransferase/alanine aminotransferase ratio) + body mass index + 2 (if diabetic) + 2 (if woman). The HSI scores were 29.50 ± 4.55, 38.08 ± 5.44, 33.61 ± 5.23, and 39.86 ± 4.13 in the MHNO, MHO, MANO, and MAO groups, respectively (p &lt; 0.05). Results: Overall, 25.55% of the participants (57.14% men) were classified as having MASLD (HSI &gt; 36). A multivariate-adjusted regression analysis revealed significantly higher HSI scores in the MAO group than in the MHNO group. Both MHO and MANO groups also had significantly higher HSI scores. The odds ratios for more severe MASLD were 2.74 (95% CI: 0.88–8.52) for the MANO group and 74.59 (95% CI: 13.29–418.68) for the MAO group compared with the MHNO group. Conclusions: These findings suggest that RTRs with obesity have a higher risk of MASLD, but even those with a normal weight and metabolic abnormalities are at increased risk.