https://www.explorationpub.com/Journals/eemd Most Recent Articles : Exploration of Endocrine and Metabolic Diseases. en-us Mon, 13 Apr 2026 14:59:20 GMT https://www.explorationpub.com/Journals/eemd/Article/101430 Hormone replacement therapy (HRT) is essential for alleviating menopausal symptoms and mitigating complications linked to type 2 diabetes mellitus (T2DM) in postmenopausal women. Studies indicate that HRT may contribute to better glycemic control, improved lipid metabolism, and enhanced kidney function, which could help lower the risk of diabetes-related complications. Early initiation of HRT near menopause has shown cognitive and metabolic benefits, while transdermal estrogen is preferred for women with cardiovascular risk due to its safer profile. However, HRT is associated with risks, including thromboembolic events and increased risks of breast and endometrial cancers, necessitating individualized evaluations. Despite its potential, significant gaps remain regarding HRT’s long-term safety and efficacy, its interaction with modern diabetes therapies, and its impact on diverse populations. The optimization of estrogen replacement therapy (ERT) strategies requires further exploration, particularly regarding patient screening, individualized treatment regimens, and personalization of care based on risk factors such as metabolic status, cardiovascular health, and diabetes severity. Current evidence supports the cautious use of HRT in strictly screened postmenopausal women with T2DM, adhering to key principles including early intervention (within 10 years of menopause), low-dose and short-duration therapy (usually < 5 years), and integration of lifestyle interventions (e.g., diet, exercise). Future research should focus on defining clear screening criteria, optimizing treatment regimens, and personalizing ERT to maximize benefits while mitigating risks. This review examines the benefits, risks, and optimization strategies of HRT in postmenopausal women with T2DM. It focuses on its metabolic, cardiovascular, cognitive, and renal effects and emphasizes personalized treatment approaches. Review Mon, 28 Apr 2025 00:00:00 GMT Butheinah A.Al-Sharafi, Samih A.Odhaib, Mon, 28 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101430 https://www.explorationpub.com/Journals/eemd/Article/10141 Not applicable. Editorial Thu, 16 Nov 2023 00:00:00 GMT Stefan R.Bornstein, Thu, 16 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/10141 https://www.explorationpub.com/Journals/eemd/Article/10142 For the past 100 years, insulin supplementation has been the mainstay of treatment for type 1 diabetes (T1D), which is characterized by progressive autoimmune-mediated loss of insulin-producing β cells in the islets of Langerhans over the last decades, technological advances in glucose monitoring and therapeutics have greatly improved the care and management of these patients. However, morbidity, mortality, and quality of life remain challenges for patients with T1D. Islet transplantation has been successfully performed, but there are several limiting factors, such as the lack of cadaveric donors and the need for lifelong immunosuppressive therapy. Therefore, there is a great medical need for alternative therapeutic approaches. In the current review, the current knowledge on novel approaches for the treatment of T1D with a focus on the potential of using chimeric antigen receptor (CAR)-T cells and natural killer (NK) cells is summarized. Review Fri, 17 Nov 2023 00:00:00 GMT CharlotteSteenblock, JiriEitler, Ioannis T.Oikonomakos, MariekeArriens, Stephan R.Künzel, TorstenTonn, Stefan R.Bornstein, Fri, 17 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/10142 https://www.explorationpub.com/Journals/eemd/Article/10144 Artificial intelligence (AI) has gained attention for various reasons in recent years, surrounded by speculation, concerns, and expectations. Despite being developed since 1960, its widespread application took several decades due to limited computing power. Today, engineers continually improve system capabilities, enabling AI to handle more complex tasks. Fields like diagnostics and biology benefit from AI’s expansion, as the data they deal with requires sophisticated analysis beyond human capacity. This review showcases AI’s integration in endocrinology, covering molecular to phenotypic patient data. These examples demonstrate AI’s potential and power in research and medicine. Review Thu, 23 Nov 2023 00:00:00 GMT Ioannis T.Oikonomakos, Ranjit M.Anjana, ViswanathanMohan, CharlotteSteenblock, Stefan R.Bornstein, Thu, 23 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/10144 https://www.explorationpub.com/Journals/eemd/Article/10143 Not applicable. Commentary Tue, 21 Nov 2023 00:00:00 GMT Stefan R.Bornstein, Lan-SunChen, WaldemarKanczkowski, Tue, 21 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/10143 https://www.explorationpub.com/Journals/eemd/Article/10145 Aim: Regenerative and curative strategies would be desirable for neurodegenerative and adrenal diseases, and multipotent adrenal stem cells are considered as promising biological tools for this purpose. Stem-like cells with the potential to proliferate and differentiate in vivo and in vitro were discovered in both cortex and medulla of the adrenal gland. Previously, it was demonstrated that nestin-positive progenitors in the cortex and medulla, play an important role under stress. In the present study, the cultivation of these cells was optimized and their growth in vitro was characterized. Methods: Primary cells from the adrenal cortex and medulla from Nes-GFP mice were isolated and the in vitro culture conditions promoting the growth of stem and progenitor cells using different 3-dimensional (3D) spheroid culture models were optimized. Results: Both cortical and medullary cells could be cultured for at least one month under several different low-adherence conditions maintaining their viability and potential to differentiate. Medullary cells grew faster than cortical cells. Endothelin did not affect the cultures. Conclusions: Adrenomedullary and adrenocortical nestin-positive progenitor cells can be cultured long-term in 3D cultures maintaining their proliferation and differentiation capabilities. Such multidimensional models can potentially be used for drug screening to develop personalized medicines or for transplantation to treat neurodegenerative disorders or adrenal diseases, such as adrenal insufficiency. Original Article Tue, 28 Nov 2023 00:00:00 GMT CharlotteSteenblock, StephanieFliedner, Giatgen A.Spinas, RacheliOfir, PatrickKugelmeier, BarbaraLudwig, NicoleBechmann, Tue, 28 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/10145 https://www.explorationpub.com/Journals/eemd/Article/101440 As women transition to menopause, their risk of cardiovascular disease increases. The risk is mediated by a cluster of abnormalities, the ‘metabolic syndrome’: dyslipidemia, insulin resistance, hypertension, and obesity. The risk is proportional to the duration of menopause, although ethnic differences were reported. Other contributing factors include estrogen deficiency, inflammatory markers, history of gestational diabetes mellitus, preeclampsia, and polycystic ovary syndrome. Susceptibility to metabolic syndrome is mediated by genetic and lifestyle factors. Intervention to prevent metabolic syndrome must begin early with physical exercise, proper nutrition, and, where indicated, nutritional supplements. Although initial results of the Women’s Health Initiative suggested that hormone therapy after menopause led to adverse outcomes, further studies, such as the Early versus Late Intervention Trial with Estradiol (ELITE) study and the Kronos Early Estrogen Prevention Study (KEEPS), showed cardiovascular benefits if hormone replacement is begun early in women not at high risk of cardiovascular disease. A personalized preventive approach must be applied. Review Wed, 24 Sep 2025 00:00:00 GMT NagamaniGumpeny, LakshmiGumpeny, Sridhar R.Gumpeny, Wed, 24 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101440 https://www.explorationpub.com/Journals/eemd/Article/10146 Aim: Epigenetic alterations have been reported in patients with pituitary tumors and those on antipsychotic drugs, which are also responsible for hyperprolactinemia. This suggests a possible role of epigenetics in the etiopathology of hyperprolactinemia. Methods: The study recruited 83 hyperprolactinemia cases with prolactin > 100 ng/mL and 65 controls. Global DNA methylation status was studied by MethylFlash Methylated DNA Quantification Kit and genome-wide methylation analysis (GWMA) by Infinium Methylation EPIC BeadChip 850K array. Results: Hyperprolactinemia cases showed significant global DNA hypermethylation compared to controls. Around 66.67% of hypomethylated and 12.9% of hypermethylated cases were on antipsychotics. Gene enrichment analysis of 5-cytosine-phosphate-guanine-3 (CpG) site-associated genes demonstrated significantly enriched major histocompatibility complex (MHC)-related protein classes and cellular components. Conclusions: The study suggested the role of epigenetics in the etiopathology of hyperprolactinemia. Original Article Thu, 23 May 2024 00:00:00 GMT Amanpreet KaurKalsi, AshutoshHalder, ManishJain, Jai BhagwanSharma, Thu, 23 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/10146 https://www.explorationpub.com/Journals/eemd/Article/10147 Diabetes and cancer are two chronic metabolic diseases with ever-increasing incidence rates worldwide. These disorders can often occur together, as diabetes presents an important risk factor for cancer and some cancers could in turn lead to diabetes. In this perspective article, many more commonalities between diabetes and cancer are highlighted, including the role of lifestyle and environmental factors in the pathogenesis, the presence of a rather long latency period before clinical diagnosis of invasive disease, as well as the ultimate progression to diabetic complications or malignant metastases. Moreover, both of these devastating disorders still lack curative treatment options, whereas several currently approved antidiabetic and anticancer drugs have been originally derived from different natural sources. However, while in the case of diabetes, the main therapeutic goal is to maintain the pancreatic islet mass by preserving β-cells survival, the major purpose of cancer therapy is to kill malignant cells and reduce the neoplastic mass of solid tumors. It is expected that both diabetes and cancer, two systemic diseases with epidemic proportions, would be managed more effectively through an integral approach, considering many different aspects related to their pathogenesis, including also lifestyle changes and dietary modifications. Perspective Thu, 23 May 2024 00:00:00 GMT KatrinSak, Thu, 23 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/10147 https://www.explorationpub.com/Journals/eemd/Article/10148 Aim: To evaluate the prediction ability for quantitative computed tomography (QCT)-based metabolic dysfunction-associated fatty liver disease (MAFLD) of four widely known hepatic steatosis algorithms, namely the fatty liver index (FLI), the hepatic steatosis index (HSI), the Framingham Steatosis index (FSI) and the Zhejiang University index (ZJU index). Methods: From July 2020 to June 2022, health checkup subjects who accepted liver fat quantification with QCT at the Health Management Center of the Second Affiliated Hospital of Chongqing Medical University were recruited in this study. MAFLD was diagnosed by using QCT-based liver fat quantification. The prediction performance of FLI, HSI, FSI, and ZJU index on MAFLD was evaluated using the area under the receiver operating characteristic curve (AUC). Results: Of a total of 4,566 subjects enrolled in this study, 48.7% were diagnosed with MAFLD. The AUC values of FLI, HSI, FSI, and ZJU index were 0.819, 0.792, 0.822 and 0.826, respectively. FLI exhibited the highest sensitivity (SN) of 79.42%, while the ZJU index demonstrated the highest specificity (SP) of 75.35%. Conclusions: All four indices (FLI, HSI, FSI, and ZJU index) have acceptable predictive performance for patients with QCT-based MAFLD. Our study suggests that the above indices have a stable ability for detecting MAFLD. Original Article Thu, 23 May 2024 00:00:00 GMT BingwuXu, CuihongLi, MengxueChen, YongZhang, Thu, 23 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/10148 https://www.explorationpub.com/Journals/eemd/Article/10149 Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is a rare genetic disorder caused by haploinsufficiency of the GATA3 gene. A very limited number of cases have been reported in the literature to date. Diagnosis is challenging as the phenotypic expression has wide heterogeneity due to variable penetrance of the underlying genetic mutation. Although the condition is inherited in an autosomal dominant pattern, sporadic cases do occur. This report presents a case of a 22-year-old female diagnosed with HDR syndrome, featuring bilateral cataract and bicornuate uterus. The GATA3 mutation detected in the patient was not identified in the family, suggesting it to be arising de novo. The present case report describes the rare phenotypic findings of bilateral cataract and bicornuate uterus associated with HDR, thus expanding the clinical spectrum of the syndrome. Case Report Mon, 27 May 2024 00:00:00 GMT RajeshChetiwal, AmitKumar, ShwetaTanwar, PriyankRastogi, Mon, 27 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/10149 https://www.explorationpub.com/Journals/eemd/Article/101410 Adult-onset testosterone deficiency (TD) in men is diagnosed by the finding of low serum testosterone levels and recognised, associated symptoms. The condition has high prevalence in men over 50 years of age, particularly those with type 2 diabetes (T2DM). Accumulating data show adult-onset TD is associated with increased mortality risk. We review the literature and consider the evidence suggesting testosterone therapy (TTh) reduces mortality, especially in men with T2DM. We previously reported that in the Burntwood Lichfield Atherstone Sutton Coldfield Tamworth (BLAST) study screened cohort of men with adult-onset TD and T2DM adult-onset TD was associated with increased mortality with TTh decreasing this higher mortality. The data hinted that the effect was greater in older men. We confirmed this observation with statistical analyses to study the effect of age on the association between adult-onset TD and mortality; Cox regression analysis demonstrated that the reduced risk (hazard ratio: 0.61, 95% CI: 0.38–0.96) following TTh was restricted to men above the median age of 65.89 years. Finally, we speculate on putative mechanisms that may mediate these associations. Heterogeneity in men with adult-onset TD is expected in view of its definition of low testosterone levels together with associated clinical phenotypes that are not always directly related. Many of these classifying phenotypes are associated with increased mortality. Thus, it is perhaps possible that mechanism(s) of all-cause mortality reduction following TTh is via the impact on these associated phenotypes such as the metabolic syndrome (MetS), hyperglycaemia, hypertension, dyslipidaemia, low haematocrit, sex hormone binding levels, erectile dysfunction, etc. We propose that further research studying the effect of TTh takes heterogeneity into account. Review Fri, 28 Jun 2024 00:00:00 GMT AmarMann, Richard C.Strange, GeoffreyHackett, CarolaKönig, SudarshanRamachandran, Fri, 28 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101410 https://www.explorationpub.com/Journals/eemd/Article/101411 Congenital adrenal hyperplasia due to 21-hydroxylase deficiency leads to high morbidity and mortality, despite the availability of life-saving corticosteroid replacement therapy. Gene therapy represents a promising potential treatment for monogenic disorders such as congenital adrenal hyperplasia, overcoming the limitations of corticosteroid replacement approaches. Adeno-associated viral vectors are currently the leading vector for direct in vivo gene delivery. However, physiological properties of the adrenal gland limit the application of adeno-associated viral vector-based gene addition strategies. To achieve durable correction in the adrenal gland, gene editing must be employed to stably introduce a genetic modification into the CYP21A2 locus. The safety of this and other gene editing approaches could be greatly improved by using lipid nanoparticles for the delivery of editing machinery mRNA. While little data exists regarding adrenocortical lipid nanoparticle targeting, physiological features of this organ (such as high relative blood flow, fenestrated endothelium, and cholesterol uptake) indicate the promise of these delivery vectors for the treatment of monogenic diseases of the adrenal cortex. This review discusses the complexities of developing gene therapy for congenital adrenal hyperplasia and explores the viability of novel gene therapy strategies in this application. Review Tue, 09 Jul 2024 00:00:00 GMT Eva B.van Dijk, Samantha L.Ginn, Ian E.Alexander, Lara E.Graves, Tue, 09 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101411 https://www.explorationpub.com/Journals/eemd/Article/101412 Stress is a state of threatened or perceived as threatened homeostasis that can be induced by various external and internal stimuli such as psychosocial factors, inflammatory or injurious conditions, and infections. In order to restore body homeostasis, adrenal glands produce and secrete glucocorticoids (GCs) and catecholamines (CAs), which are the main stress hormones that support the survival and adaptation of the organisms to the new environment. In contrast to the rather beneficial impact of acute and short-lasting stress, chronic stress and related dysregulation of the stress system is implicated in the development of many non-communicable diseases, including cancer. Particularly, ever-increasing experimental and clinical evidence implicates the involvement of CAs and GCs as well as the overexpression of their receptors in the activation of the major pathways involved in tumour development, metastasis, and resistance to various therapies. More importantly, results of experimental and epidemiological studies revealed that overexposure to stress hormones during pre- and early postnatal life might induce life-long or even transgenerational dysregulation of the stress system and predispose it to the development of various tumours. Although the exact mechanisms involved in the latter process are not yet fully known, it has been demonstrated that GC-induced epigenetic modifications can change the expression of several key genes involved in the regulation of the stress system, tumour initiation, and epigenetic imprinting. When such alterations occur in stem/progenitor cells (SPCs), this might not only lead to long-term dysfunction of the stress system but might promote the generation of cancer stem cells (CSCs). This review article discusses a hypothesis that stress hormones-mediated epigenetic reprograming of various SPCs during sensitive developmental periods, might contribute to their dysfunction and increased sensitivity to malignant transformation, thereby promoting tumorigenesis. Review Tue, 16 Jul 2024 00:00:00 GMT WaldemarKanczkowski, MarikoSue, AgnèsWlodarczyk, George P.Chrousos, Tue, 16 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101412 https://www.explorationpub.com/Journals/eemd/Article/101413 The escalating prevalence of diabetes poses a significant health concern. Uncontrolled diabetes leads to a multitude of complications. A comprehensive management plan and continual adaptation of guidelines is needed. The American Diabetes Association (ADA) is a guiding force in this domain, providing diabetes care recommendations for clinicians, laboratorians, researchers, and policymakers since 1989. The latest ADA guidelines present both challenges and opportunities for laboratories. The increased emphasis on glycated hemoglobin (HbA1c) testing for early diagnosis and personalized monitoring is expected to increase testing volumes, potentially leading to a rise in point-of-care testing. Ensuring standardized testing procedures becomes paramount to maintaining consistent and reliable results across laboratories. Moreover, laboratories may need to expand their test menus to accommodate the growing demand for personalized medicine approaches and collaborate closely with healthcare providers to support informed decision-making. This commentary provides a focused analysis of the 2024 ADA guidelines for the laboratory assessment of diabetes. Commentary Tue, 23 Jul 2024 00:00:00 GMT DiptiTiwari, Tar ChoonAw, Tue, 23 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101413 https://www.explorationpub.com/Journals/eemd/Article/101414 Aim: Current diabetes guidelines recommend people with gestational diabetes mellitus (PwGDM) use primarily blood glucose meters (BGM) for diabetes management. We evaluated glycemic trends and guideline-recommended glycemic targets achieved in PwGDM using a diabetes app with a family of Bluetooth® connected BGMs. Methods: Anonymized glucose and app analytics data from 26,382 PwGDM were sourced from a server. Data from their first 7-days using the app with connected BGMs was compared to 7-days prior to a 10-week timepoint. Results: Percent fasting readings in range (RIR, < 5.3 mmol/L) improved by +20.3 percentage points in the overall population. Improved glucose RIR (3.5 to 7.8 mmol/L) (+8.3 percentage points), mean blood glucose (BG, –0.59 mmol/L), and fasting RIR (+33.2 percentage points) were observed in those with baseline mean BG ≥ 6.1 mmol/L. Improvements in mean BG of –0.32 to –2.36 mmol/L, and RIR of +3.0 to +38.3 percentage points correlated with higher baseline mean BG ≥ 6.1 to ≥ 7.8 mmol/L. Only 58.5% of PwGDM with baseline mean BG ≥ 6.1 mmol/L had > 80% RIR at baseline, which improved to 79.5% at 10 weeks. PwGDM averaged 17 app sessions and 90 minutes per week on the app. Conclusions: PwGDM engaged with the diabetes app and connected BGM, facilitating attainment of glycemic targets, an especially important outcome for those with higher mean glucose at baseline. Original Article Wed, 24 Jul 2024 00:00:00 GMT MikeGrady, HilaryCameron, ElizabethHolt, Wed, 24 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101414 https://www.explorationpub.com/Journals/eemd/Article/101415 Aim: To evaluate changes in quality of life via the ageing male symptom scale (AMSS) and somatic, psychological, and sexual sub-scales following testosterone undecanoate (TU) or placebo (P) treatment in men with type 2 diabetes mellitus (T2DM) and adult-onset testosterone deficiency (TD) via a re-analysis of the BLAST (Burntwood, Lichfield, Atherstone, Sutton Coldfield, and Tamworth) randomised controlled trial (RCT). Methods: Analysis of data from the BLAST RCT in men with T2DM and adult-onset TD was performed. Summation baseline and study-end AMSS data were available in 170 men (94: P; 76: TU) with subscale data available in 82 men. Rank-sum and sign-rank tests determined inter/intra-group differences, whilst linear/multiple regression models identified predictors of AMSS change. Results: AMSS improved significantly in P [–2 (median), p = 0.010] and TU [–6 (median), p < 0.0001)] arms, with greater improvement observed in men on TU (p = 0.014). No significant change was seen in either arm with baseline AMSS < 27 (asymptomatic). TU was significantly associated with AMSS improvement in all symptomatic AMSS categories. Improvement in the P arm was confined to men with baseline AMSS > 49. In the cohort with subscale AMSS data, TU was associated with improvements in somatic, psychological, and sexual subscales, whilst improvement was limited to the somatic subscale in the men on P. TU (reference: P) and higher baseline AMSS were significantly and independently associated with AMSS improvement. The improvement in summation AMSS associated with TU (reference: P) was only evident in men with mild depression and no anxiety (based on baseline Hospital Anxiety and Depression Scale data). Conclusions: TU appeared associated with improved AMSS (summation and subscales) in men with T2DM and adult-onset TD demonstrating symptoms (AMSS ≥ 27) with this benefit mediated by levels of depression and anxiety (European Union Clinical Trials Register, EudraCT 2008-000931-16). Original Article Tue, 13 Aug 2024 00:00:00 GMT PravinathRamachandran, MichaelZitzmann, Carola S.König, JosephMulhern, SudarshanRamachandran, GeoffreyHackett, Tue, 13 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101415 https://www.explorationpub.com/Journals/eemd/Article/101416 Stress hormones, namely glucocorticoids, have diverse actions throughout the body in regulating development, tissue metabolism, inflammation, circadian rhythms, and skeletal homeostasis. While endogenous glucocorticoid levels are important to support bodily homeostasis, chronically elevated levels can cause damage to tissues and drive diseases including bone loss (i.e., osteoporosis), myopathy (i.e., sarcopenia) and metabolic disturbances (i.e., glucose intolerance, diabetes, and abnormal fat accrual). There is substantial evidence that basal glucocorticoid levels increase during ageing while at the same time the amplitude of the diurnal variation in glucocorticoid secretion decreases. However, the significance of these changes for skeletal health is not well understood and has only recently been studied in more detail. Evidence from genetically modified mouse models indicates that changes in glucocorticoid signaling associated with ageing induce bone loss, sarcopenia and drive osteoarthritic joint disease. These studies provide important insights into the role of glucocorticoids in age-related skeletal diseases which will aid in the development of novel treatments especially needed for osteoarthritis which disproportionally affects the elderly. Review Fri, 16 Aug 2024 00:00:00 GMT EugenieMacfarlane, HongZhou, Markus JoachimSeibel, Fri, 16 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101416 https://www.explorationpub.com/Journals/eemd/Article/101417 A 74-year-old male patient with beta thalassemia minor presented in 2022 for a follow-up of osteoporosis diagnosed prior to 2004. At the time of presentation, his medical history included: radiation exposure to his head and neck, goiter, prostate cancer status post resection in 2019 without a history of anti-androgen therapy, and atrial fibrillation, for which he had been prescribed apixaban since 2021. Treatment with risedronate occurred from approximately 2004 to about 2011, with improvement in bone density to osteopenia. He had also taken vitamin D and calcium supplementation and engaged in regular weight-bearing exercise. The patient had no other known risk factors for decreased bone mineral density preceding the onset of his osteoporosis, and a previous workup for secondary causes of his osteoporosis etiology proved negative. We propose that beta thalassemia minor is potentially a risk factor for osteopenia and osteoporosis, and that bisphosphonates can be considered for management when therapeutic intervention is indicated. Even in the absence of other known risk factors, clinicians should consider periodically screening beta thalassemia minor patients with DXA for evaluation of bone health. Case Report Fri, 01 Nov 2024 00:00:00 GMT FeliciaWoron, TheaAnderson, CatrionaHong, ParvathyMadhavan, Fri, 01 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101417 https://www.explorationpub.com/Journals/eemd/Article/101420 Not applicable. Correction Fri, 20 Dec 2024 00:00:00 GMT Kailah M.Charles, Matthew A.Nazari, AbhishekJha, SaraTalvacchio, Mickey J. M.Kuo, MayankPatel, AlexanderLing, Ali S.Alzahrani, TamaraProdanov, AlbertaDerkyi, AliceChen, JohnGlod, Jaydira DelRivero, KarelPacak, Fri, 20 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101420 https://www.explorationpub.com/Journals/eemd/Article/101419 The clinical case presented describes a 44-year-old woman with a history of mucinous carcinoma in the right breast, who is diagnosed with a pituitary adenoma. Physical examination revealed signs of acromegaly, such as macroglossia and palmar hyperhidrosis. Hormonal tests were performed and showed elevated levels of insulin-like growth factor type 1 (IGF-1). The patient received GnRH analogues for breast cancer; and started medical treatment with somatostatin analogues for acromegaly, which provided improvement in symptoms. Pituitary bleeding was detected during hormone treatment, which caused the growth of the adenoma, causing it to contact the optic chiasm, although no symptoms of pituitary apoplexy were present. Transsphenoidal endoscopic surgery was performed to remove the adenoma, and the diagnosis of pituitary adenoma was confirmed by pathology. The importance of the evaluation of comorbidities in patients with acromegaly is discussed. Pituitary apoplexy as an uncommon complication of pituitary adenomas, which may be associated with the use of GnRH analogues, is addressed. Pre-surgical medical treatment in acromegaly is also discussed, highlighting the importance of a comprehensive assessment of prognostic factors and appropriate treatment selection to improve clinical outcomes. In conclusion, the importance of a multidisciplinary and personalized approach in the management of patients with GH-producing pituitary adenomas to improve quality of life and clinical outcomes is highlighted. Case Report Wed, 27 Nov 2024 00:00:00 GMT IgnacioJiménez Hernando, LauraGonzález Fernández, Wed, 27 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101419 https://www.explorationpub.com/Journals/eemd/Article/101421 Aim: Metabolic syndrome (MetS) is associated with chronic conditions, including type 2 diabetes mellitus (T2DM) and cardiovascular disorders. New markers are needed for the early detection and successful treatment of MetS, especially in patients with T2DM. The serum uric acid-to-creatinine ratio (UCR) and waist-to-height ratio (WHR) are novel markers in various chronic metabolic disorders. We aimed to compare WHR, UCR, and other metabolic and laboratory markers in T2DM patients with and without MetS. Methods: Patients with T2DM who visited the outpatient clinics of our institution were enrolled in the study. Total diabetic subjects were 239 of which 180 were in MetS group while 59 were in without MetS group. Data from both study groups were compared. Results: The serum UCR in the MetS and control groups was 6.3 ± 2.1 and 5.8 ± 1.6, respectively (p = 0.04). The WHR in the MetS and control groups was 0.65 (0.47–0.87) and 0.62 (0.35–0.84), respectively (p < 0.001). Significant positive correlations were observed between UCR and triglycerides (r = 0.17, p = 0.009), waist circumference (r = 0.13, p = 0.046), hip circumference (r = 0.18, p = 0.006), BMI (r = 0.2, p = 0.002), and GFR (r = 0.4, p < 0.001). Similarly, significant positive correlations were noted between WHR and systolic blood pressure (r = 0.12, p = 0.049), weight (r = 0.5, p < 0.001), BMI (r = 0.7, p < 0.001), and UCR (r = 0.12, p = 0.047). In the ROC analysis, the sensitivity and specificity of WHR (when higher than 0.64) in detecting MetS were 72% and 54%, respectively (AUC: 0.69, p < 0.001, 95% CI: 0.61–0.77). Conclusions: We propose that WHR and UCR could be valuable tools for the early detection of MetS in patients with T2DM. The ease and low cost of evaluating WHR and UCR make them practical markers for monitoring and diagnosing MetS. Original Article Fri, 10 Jan 2025 00:00:00 GMT ElifBasaran, GulaliAktas, Fri, 10 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101421 https://www.explorationpub.com/Journals/eemd/Article/101422 Type 2 diabetes mellitus (DM) and hypertension (HT) are common major cardiovascular disease (CVD) risk factors. They share common pathophysiological mechanisms and are commonly co-existent. Prevalence of HT is increased among diabetic patients but also DM is more common in hypertensive patients. CVD risk increases multiplicatively in coexistence of HT and DM. Lowering blood pressure (BP) has been shown to be associated with improved morbidity related to both macro- and micro-vascular complications. Although there is debate about target BP levels, in many randomized controlled trials and guidelines a goal of < 130/80 mmHg is advocated in patients with DM, if well tolerated. However, an individualized approach should be cared for depending on risk factors, co-morbidities, and frailty of patients. Lifestyle modifications including weight loss, regular exercise, avoiding smoking and excessive alcohol consumption, and a healthy diet including limitation of salt and fat and total energy intake, are important both as a part of preventive therapy and treatment modality for both DM and HT. Among antihypertensive drugs angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) are warranted due to their potential advantages for slowing albuminuria and progression to kidney failure which is more common in DM. Usually, their combination with calcium-channel blockers (CCBs) or thiazide/thiazide-like diuretics, in a step-wise manner, is recommended. Resistant HT is more common in DM and requires the addition of mineralocorticoid receptor antagonists (MRAs). New antidiabetic drugs like glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to lower BP. Apart from their antihypertensive effects they also improve CVD and renal outcomes. There’re ongoing new trials for new agents. Development of more potent and longer-term effective BP lowering drugs, single pill multiple drug combinations of antiHT agents and combination of antiHT agents with glucose-lowering and antilipidemic agents will probably improve compliance to treatment and achievement of goals in diabetic patients. Review Wed, 05 Feb 2025 00:00:00 GMT YilmazGunes, Wed, 05 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101422 https://www.explorationpub.com/Journals/eemd/Article/101423 Metabolic disorders are due to a deficiency of enzymes, which can severely impact health or cause serious complications without treatment. This study aimed to identify the molecular causes of an infant death who had been hospitalized with complicated health problems and metabolism syndrome. Whole-exome sequencing (WES) was used to screen pathogenic variants in the patient’s genome, followed by examination of variants segregation in her parents. The WES analysis identified two homozygous variants, c.[614C>G; 649A>G] in the HMGCL gene of the patient. These two variants co-locate within the exon 7 of the HMGCL gene, resulting in 2 amino acid substitutions, p.[T205S; M217V], in the conservative region of enzyme protein. Sanger sequencing showed that the patient’s unaffected mother and father carried one mutant allele of the HMGCL gene containing two c.[614C>G; 649A>G] variants. The HMGCL gene encodes the 3-hydroxy-3-methylglutaryl-CoA lyase enzyme, which is critical in the ketogenic pathway. The deficiency of this enzyme was reported to be a life-threatening illness in the neonatal period, and two variants detected in this study were also found in a Japanese patient with sudden, unexpected death in infancy. The frequency of these two variants in the Vietnamese in-hour database and their further functional analysis were also reported in this study. The results of this study have explored the molecular etiology that causes the severe, deadly condition of the patient and provide an understanding of the risk of disease in her family. Case Report Fri, 14 Feb 2025 00:00:00 GMT Hong ThuNguyen-Huu, Khanh LinhNguyen, Phuong NhungVu, Hai HaNguyen, Fri, 14 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101423 https://www.explorationpub.com/Journals/eemd/Article/101418 Pheochromocytomas (PCCs) and paragangliomas (PGLs; together PPGLs) are uncommon neuroendocrine tumors arising from adrenal medullary chromaffin cells and sympathetic/parasympathetic paraganglia. Though PPGLs predominate in adult populations, pediatric cases of PPGLs represent more aggressive disease outcomes with 12% being diagnosed as metastatic. Metastatic disease (spread to bone, lung, lymph nodes, or liver) occurs in a subset of PPGLs, ranging from 15% to 17% depending on the underlying pathogenic variants. Historically, pulmonary metastases present clinically as multiple small lesions; however, cases of PPGLs with innumerable small metastases (a miliary pattern) overwhelming lung parenchyma define a novel yet exceptionally challenging disease presentation. This pattern of pulmonary lesions upon treatment and/or cellular lysis may lead to both respiratory decompensation as well as prolific catecholamine release, incurring significant morbidity and mortality if not appropriately managed. Of the 2,649 PPGL patients enrolled in our protocol from January 1, 2000, to April 30, 2023, 500 had metastatic disease, 122 were children/adolescents, and 3 of the 122 children/adolescents had extensive pulmonary metastatic disease. All three adolescent patients with extensive pulmonary metastases had cluster 1 PPGLs and suffered hypoxemia (due to pulmonary metastases) leading to overactive hypoxia signaling and catecholamine-induced signs and symptoms [among them hypertension and/or tachyarrhythmia(s)]. Interventions including surgery, chemotherapy, and radiotherapy were pursued. Two patients achieved disease stability, while one patient succumbed to disease. Ultimately these divergent outcomes emphasize the importance of recognizing poor prognostic factors and aggressive disease early, to select appropriate treatments. Optimal management of these patients must consider complications of catecholamine excess and the profound influence of hypoxia. Herein, we describe three adolescent cases of extensive pulmonary metastatic PPGL and the unique clinical challenges faced in treating these tumors alongside relevant literature to provide guidance on appropriate interventions (ClinicalTrials.gov identifier: NCT00004847). Case Report Fri, 15 Nov 2024 00:00:00 GMT Kailah M.Charles, Matthew A.Nazari, AbhishekJha, SaraTalvacchio, Mickey J. M.Kuo, MayankPatel, AlexanderLing, Ali S.Alzahrani, TamaraProdanov, AlbertaDerkyi, AliceChen, JohnGlod, Jaydira DelRivero, KarelPacak, Fri, 15 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101418 https://www.explorationpub.com/Journals/eemd/Article/101424 The accumulation of adipose tissue is associated with metabolic disorders, including insulin resistance, type 2 diabetes (T2D), dyslipidemia, metabolic syndrome, and cardiovascular diseases (CVD). Menopause might predispose women to increase body weight and adipose tissue, and decrease lean muscle mass. Furthermore, postmenopausal women display fat mass redistribution with greater accumulation in the visceral area mainly due to hormonal shifts that result in a higher testosterone/estradiol ratio. These effects are associated with a less favorable adipokine profile, dyslipidemia, insulin resistance, and cardiac dysfunction after menopause. Fat mass is determined by the balance between the storage of triacylglycerol (TAG) (lipogenesis) and the removal of stored TAG (lipolysis) in combination with the differentiation of new adipocytes (adipogenesis). Disturbances in adipose tissue dynamics lead to an increase in lipogenesis (hypertrophy) and/or in adipogenesis (hyperplasia) to accommodate excess energy intake. While large adipocytes are dysfunctional and have greater secretion of inflammatory adipocytokines, small adipocytes are healthier and associated with metabolic improvements. Different strategies can be used to prevent or reduce body weight gain and fat mass, as well as to maintain healthy adipose tissue; however, due to robust evidence, lifestyle interventions should be pillars in this process. This review provides a comprehensive summary of findings on the role of a balanced diet and physical exercise in improving body composition and promoting healthy adipose tissue in postmenopausal women. Review Fri, 14 Mar 2025 00:00:00 GMT BrunoVecchiatto, Thiago L.Castro, Natália Juliana RamosFerreira, Fabiana S.Evangelista, Fri, 14 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101424 https://www.explorationpub.com/Journals/eemd/Article/101425 Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as a global health crisis, affecting over 30% of the population and demanding urgent attention. This redefined condition, previously known as non-alcoholic fatty liver disease (NAFLD), reflects a deeper understanding of the intricate interplay between metabolic dysfunction and liver health. At the heart of MASLD lies the troubling accumulation of triglycerides (TGs) in hepatocytes, which precipitates insulin resistance and oxidative stress, ultimately leading to more severe forms like metabolic dysfunction-associated steatohepatitis (MASH). Excitingly, recent research has spotlighted the farnesoid X receptor (FXR) as a groundbreaking therapeutic target. FXR not only regulates lipid metabolism but also combats inflammation and insulin resistance, making it a potential game-changer in the fight against MASLD. With only one FDA-approved drug, resmetirom, currently available, the exploration of FXR agonists opens new avenues for innovative treatments that could revolutionize patient care. By harnessing the power of FXR to restore metabolic balance and integrating advanced strategies like lipidomics and fatty acid profiling, we stand on the brink of transforming how we approach MASLD and its associated complications, paving the way for a healthier future. This review delves into the promising role of FXR in combating MASLD and its implications for related metabolic disorders, emphasizing the urgency for advanced strategies to detect and manage this burgeoning epidemic. Review Wed, 26 Mar 2025 00:00:00 GMT PirangiSrikanth, Khaja MoinuddinShaik, VijayPatibandla, DeepakKumar, SukhenduNandi, Wed, 26 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101425 https://www.explorationpub.com/Journals/eemd/Article/101426 The glucocorticoid receptor alpha (GRα), a vital component of the ancient glucocorticoid (GC) signaling system, is essential for vertebrate survival. It regulates fertility, fetal development, organ function, vascular and neural integrity, metabolism, immune responses, and stress adaptation. While GRα’s anti-inflammatory properties have been acknowledged since the mid-20th century, its crucial role as the master regulator of homeostatic corrections in both health and critical illness has only recently come to light. In critical illness, GRα facilitates a seamless transition through three essential phases of homeostatic correction. Initially, in the Priming Phase, it activates immune responses and mobilizes energy reserves to defend against stressors like infection and injury, enhancing glucose metabolism, supporting mitochondrial function, and strategically deploying immune cells to areas of damage. Next, during the Modulatory Phase, GRα fine-tunes inflammatory responses, manages oxidative stress, regulates vascular tone, and maintains cellular integrity. Finally, in the Restorative Phase, GRα plays a crucial role in resolving inflammation, initiating tissue repair, supporting cellular regeneration, facilitating debris clearance, and reestablishing anatomical and physiological balance for long-term recovery. GRα coordinates complex molecular interactions, including co-regulation with pro-inflammatory transcription factors, ensures mitochondrial stability, and metabolic balance under stress. However, depleted bioenergetic and micronutrient reserves in critically ill patients can impair GRα’s capacity, increasing morbidity and mortality risks. This review highlights the need to reassess current GC treatment strategies and integrate micronutrient support to optimize GRα function. Such an approach could strengthen immediate immune defenses, enhance long-term recovery, reduce GC dose and duration, and minimize adverse effects. Review Fri, 28 Mar 2025 00:00:00 GMT Gianfranco UmbertoMeduri, Fri, 28 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101426 https://www.explorationpub.com/Journals/eemd/Article/101427 Obesity is a multifactorial disease linked to many comorbidities and has an impact on brain health. It is also known that obesity disrupts the endocannabinoid (eCB) system in the central nervous system and in the periphery, which complicates the underlying mechanisms behind obesity. However, weight loss through lifestyle interventions or bariatric surgery may alleviate obesity-related comorbidities, as well as restore eCB tone. Several studies have reported a decrease in circulating eCBs following weight loss, likely due to the positive association of these mediators with fat mass. However, further research is needed to clarify whether this reduction is a consequence of weight loss or plays a role in facilitating it. This review explores changes in circulating eCBs following weight loss and their potential roles in cerebral homeostasis and the reward system. It examines how lifestyle modifications and bariatric surgery may influence central eCB signalling and contribute to long-term weight loss success. Understanding the mechanisms behind improved brain function after weight loss could provide insights into optimizing obesity treatments. Review Tue, 08 Apr 2025 00:00:00 GMT GabrielleSt-Arnaud, TristanRocheleau, AlainVeilleux, VolatianaRakotoarivelo, VincenzoDi Marzo, Tue, 08 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101427 https://www.explorationpub.com/Journals/eemd/Article/101428 Diabetes mellitus is a major risk factor for both cardiovascular and chronic kidney disease (CKD) while CKD is also associated with cardiovascular morbidity. In fact, cardiovascular disease is the leading cause of death in patients with diabetes mainly from heart failure or myocardial infarction. The newer therapeutic agents in diabetes have positive impact on both cardiovascular and renal outcomes. Thus, the American Diabetes Association (ADA)’s annual update on the Standards of Medical Care in Diabetes is an important resource for all caregivers involved in diabetes management as it incorporates the latest scientific research, clinical evidence, and emerging technologies in diabetes management. The 2025 guidelines present significant updates that reflect a deeper understanding of diabetes management, emphasizing expanded usage of technologies such as continuous glucose monitoring, personalized pharmacological approaches, and lifestyle interventions. This commentary provides an analysis of the key updates in the 2025 ADA guidelines exploring implications for clinical practice, laboratory assessments, and public health policy. Where relevant, comparisons to the 2024 version will be made. Commentary Tue, 15 Apr 2025 00:00:00 GMT DiptiTiwari, Wann JiaLoh, Tar ChoonAw, Tue, 15 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101428 https://www.explorationpub.com/Journals/eemd/Article/101429 Pediatric adrenocortical tumors (pACTs) are rare endocrine neoplasms with variable prognosis, commonly associated with germline pathogenic variants (PVs) in the tumor suppressor gene TP53. Here, we report the case of a 3.1-year-old female presenting with virilization and Cushing syndrome due to a left-sided adrenal mass. The tumor was completely resected and confirmed as stage II adrenocortical carcinoma (ACC) based on the Wieneke index. Comprehensive molecular profiling revealed heterozygous germline PVs in BRCA2 [c.9382C>T p.(Arg3128*)] and CHEK2 [c.1232G>A p.(Trp411*)]. These findings suggest a potential role of impaired DNA damage repair in ACC pathogenesis, as both PVs are associated with hereditary breast and ovarian cancer (HBOC) syndromes and genomic instability. This case expands the genetic spectrum of pACT and underscores the importance of advanced molecular analyses in identifying rare germline alterations that may inform personalized treatment strategies and cancer prevention programs. Although no additional treatment was required in this case, BRCA2 status highlights the potential for tailored therapeutic approaches, including poly(ADP-ribose) polymerase (PARP) inhibitors, in selected patients. Further research is warranted to explore the specific contributions of BRCA2 and CHEK2 PVs to ACC tumorigenesis and their implic ations for targeted therapies. Case Report Thu, 17 Apr 2025 00:00:00 GMT Victoria E.Fincke, IrmengardSax, MarinaKunstreich, Monika M.Golas, Thomas G.Hofmann, MatthiasSchlesner, RainerClaus, AntjeRedlich, Pascal D.Johann, MichaelaKuhlen, Thu, 17 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101429 https://www.explorationpub.com/Journals/eemd/Article/101431 Iatrogenic hypoparathyroidism is a serious complication that can arise from neck surgery, predominantly during thyroidectomy, parathyroidectomy, and laryngectomy; it can be transient or permanent, requiring lifelong treatment. Early detection and treatment are crucial to prevent severe hypocalcemia, which is potentially fatal. This case report describes a 59-year-old male with a history of well-differentiated squamous cell carcinoma of the vocal cords who developed severe postoperative hypoparathyroidism following total laryngectomy with right hemithyroidectomy. Despite initial treatment with cholecalciferol by nasogastric tube, the patient experienced recurrent severe hypocalcemia, requiring intravenous administration of calcitriol due to his inability to swallow. This case highlights the risk factors for triggering postoperative hypoparathyroidism, such as previous surgery or radiotherapy in the cervical region, underlines the importance of careful monitoring of postoperative hypoparathyroidism and proposes the use of intravenous calcitriol as an effective strategy in acute treatment when oral administration is not feasible. Case Report Fri, 09 May 2025 00:00:00 GMT IgnacioJiménez Hernando, LauraGonzález Fernández, MartaPérez Noguero, Fri, 09 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101431 https://www.explorationpub.com/Journals/eemd/Article/101432 The glucocorticoid receptor (GR) signaling pathway is essential for supporting the integrity of the intestinal barrier, regulating the gut microbiome, and preserving systemic homeostasis in critically ill patients. GR signaling limits bacterial translocation and systemic inflammation by suppressing pro-inflammatory cytokines, reinforcing tight junction proteins, and promoting epithelial renewal. Additionally, physiological levels of glucocorticoids (GCs) stimulate glutamine and proline metabolism, supporting intestinal maturation, with potential clinical relevance. GR signaling modulates inter-organ communication via the gut-lung and gut-brain axes, improving outcomes. Probiotics enhance GC therapy by restoring microbial balance, increasing short-chain fatty acid (SCFA) production, and modulating immune responses. Vitamins A, C, D, and E contribute to gut resilience by stabilizing tight junctions, mitigating oxidative stress, and strengthening mucosal immunity. Specifically, vitamin D balances T-cell subsets and promotes antimicrobial peptides; vitamin C supports collagen synthesis, antioxidant defenses, and immune function; vitamin A promotes immune tolerance and epithelial regeneration; and vitamin E mitigates oxidative damage and excessive cytokine release. GCs, probiotics, and vitamins counteract key drivers of critical illness, including hyperinflammation and dysbiosis, while maintaining strong safety profiles. This integrative approach leverages these interventions’ distinct yet complementary roles to provide a multi-layered defense against gut dysfunction. GCs reduce excessive inflammation and restore immune balance; probiotics enhance microbial diversity and strengthen gut-associated immunity; and vitamins support epithelial integrity and antioxidant defenses. Targeting multiple pathways simultaneously protects the gut barrier and modulates systemic immunity, potentially reducing complications such as sepsis, multiple organ dysfunction syndrome (MODS), and prolonged intensive care unit (ICU) stays. Incorporating these elements into critical care practice offers a novel strategy to mitigate gut dysfunction, reduce systemic inflammation, and enhance immune resilience. This approach may lower infection rates, decrease the incidence of sepsis and MODS, and accelerate recovery by targeting GR signaling, restoring microbial homeostasis, and reinforcing epithelial integrity. Review Thu, 15 May 2025 00:00:00 GMT Gianfranco UmbertoMeduri, Thu, 15 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101432 https://www.explorationpub.com/Journals/eemd/Article/101433 Aim: This study aimed to evaluate and compare the therapeutic effects of resmetirom, semaglutide, and obeticholic acid (OCA) on non-alcoholic fatty liver disease (NAFLD) activity score (NAS) and fibrosis progression across three distinct metabolic dysfunction-associated steatohepatitis (MASH) models. A secondary objective was to assess model-specific variations in drug efficacy to inform future preclinical model selection for MASH research. Methods: The Gubra-Amylin NASH (GAN) diet-induced obesity (DIO)-MASH model was induced by the GAN diet in C57BL/6 mice for 24 weeks, followed by semaglutide and resmetirom treatment for 4 weeks. The ob/ob-MASH model was induced by the GAN diet in ob/ob mice for 6 weeks, followed by semaglutide and resmetirom treatment for 4 weeks. GAN-carbon tetrachloride (CCL4) MASH model was induced by 10 weeks of GAN diet and followed by 4 weeks of CCL4 in C57BL/6 mice, resmetirom and OCA were given in the last 4 weeks. Body weights, serum biochemical markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipids], histopathological NAS scores, fibrosis staging, and α-smooth muscle actin (α-SMA) expression were analyzed. Results: In the GAN DIO-MASH model, both semaglutide and resmetirom reduced NAS significantly, and resmetirom but not semaglutide reduced α-SMA expression. In the ob/ob MASH model, treatment with semaglutide and resmetirom reduced NAS. Semaglutide significantly reduced α-SMA expression. In the GAN-CCL4 MASH model, both resmetirom and OCA significantly reduced MASH progression, resmetirom reduced liver fibrosis and α-SMA expression while OCA reduced α-SMA expression only. Conclusions: Resmetirom, semaglutide, and OCA exhibited model-dependent efficacy in attenuating MASH progression. Although all agents improved the NAS, their antifibrotic effects diverged significantly: resmetirom demonstrated pan-model efficacy, semaglutide selectively reduced α-SMA expression in leptin-deficient models, and OCA showed minimal impact on fibrosis biomarkers. These observations highlight the critical importance of preclinical model selection for MASH therapeutic development, particularly when assessing fibrosis-targeted interventions. Original Article Tue, 24 Jun 2025 00:00:00 GMT RufengZhang, XuechengLi, XiaoshuangLiang, YuhuanKuang, XiangruChen, YunchaoNiu, LingYe, DiruiLi, XiaofeiZhou, ChunliSun, Tue, 24 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101433 https://www.explorationpub.com/Journals/eemd/Article/101434 Aim: Hormone pulsatility is an important aspect of the hypothalamic-pituitary-adrenal (HPA) axis in health and disease. We use the properties of simple mathematical models to determine whether hormone pulsatility reflects the presence of a time delay in the production of hormones and/or is related to the impulsive nature of hormone secretion. Methods: The predictions of two models for HPA pulsatility are compared. The first model assumes pulsatility arises because of a time delay in the synthesis of glucocorticoids (GCs). The second model suggests that pulsatility reflects the impulsive nature of hormone secretion. The generation of oscillations by the second mechanism does not require a time delay. Results: The time delay for the synthesis of GC (0–10 minutes) may not be long enough to account for the oscillations in adrenocorticotrophin (ACTH) and GC observed with constant corticotrophin-releasing hormone (CRH) infusion in rats. A simple mechanism for hormone release, illustrated using an integrate-and-fire mechanism, reproduces the observed hormone pulsatility. Conclusions: The water solubility of CRH and ACTH draws attention to the role played by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in the calcium-dependent exocytosis of peptide hormones. Abnormalities in SNARE proteins are anticipated to cause changes in the amplitude modulation of ACTH and CRH hormone pulses. In mice, a mutation in a SNARE protein causes abnormalities in the HPA axis. Mutations in SNARE proteins occur in many neurodegenerative and neuropsychiatric diseases. Abnormalities in HPA function also occur in these disorders. The identification of SNARE protein mutations in exosomes in serum and cerebrospinal fluid in humans may make it possible to determine whether there exists a causal relationship between an SNARE protein mutation and abnormalities in the HPA axis in this patient group. Original Article Tue, 24 Jun 2025 00:00:00 GMT JohnMilton, AlexanderChurilov, Tue, 24 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101434 https://www.explorationpub.com/Journals/eemd/Article/101435 Diabetes affects approximately 463 million people worldwide, and this number is projected to reach 700 million by 2045. The most significant cause of increased mortality among diabetic patients is cardiovascular disease, with heart failure (HF) being one of the most commonly observed conditions within this group. Type 2 diabetes mellitus (T2DM), characterized by insulin resistance, accounts for more than 90% of all diabetes cases. Patients with T2DM have twice the risk of developing HF compared to non-diabetic individuals. The connection between diabetes mellitus (DM) and HF extends beyond the complications of ischemic heart disease, encompassing metabolic disturbances such as glucose toxicity and lipotoxicity resulting from insulin resistance, as well as vascular endothelial dysfunction, microcirculatory abnormalities, and capillary insufficiency. Lifestyle modifications for individuals with T2DM involve engaging in regular physical activity, maintaining a balanced diet, quitting smoking, and reducing alcohol consumption. For patients with reduced ejection fraction HF [heart failure with reduced ejection fraction (HFrEF)] and T2DM, guideline-recommended medical therapies [including ARNI, angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium glucose co-transporter-2 (SGLT2) inhibitors] should be considered. Recent large randomized controlled trials have demonstrated that SGLT2 inhibitors improve cardiovascular outcomes, including all-cause mortality, independent of diabetes status. This review will focus on the epidemiology, pathophysiology, risk factors for HF development, and treatment approaches in diabetic patients, particularly those with T2DM and systolic HF. Mini Review Tue, 01 Jul 2025 00:00:00 GMT IsaSincer, Tue, 01 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101435 https://www.explorationpub.com/Journals/eemd/Article/101436 Aim: This analysis examined the prevalence and incidence of type 2 diabetes mellitus (T2DM) and co-morbid lung disease in the UK Biobank population. Methods: Non-communicable inflammatory lung diseases, body mass index (BMI), age, glycated haemoglobin (HbA1c), sex, smoking status, diabetes status, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) data were obtained. Participants were categorised by BMI: lean (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥ 30 kg/m2). Fisher’s exact test identified lung disease prevalence and incidence. Kruskal-Wallis assessed lung function variance and its correlation with HbA1c. Cox regression analysed the impact of confounders on time to lung disease events. Results: Overweight and obesity increased the prevalence and incidence of chronic obstructive pulmonary disease, asthma, and bronchitis, but this was not evident in cases of bronchiectasis in those without T2DM (P < 0.05–0.0001). Conversely, T2DM increased lung disease risk across all BMIs (P < 0.0001) and reduced FEV1 and FVC even after HbA1c normalisation (P < 0.0001). FEV1 and FEV1/FVC were negatively correlated with HbA1c. Age, diabetes, being a woman, smoking, reduced FEV1 and FEV1/FVC ratio, but not BMI, were factors in lung disease development in T2DM. Conclusions: Inflammatory lung conditions are more common in T2DM patients, regardless of BMI. The pattern of lung decline suggests restrictive impairment, despite a high risk of obstructive disorders. This data adds to the evidence that the lungs are a target organ of diabetes damage. Original Article Fri, 04 Jul 2025 00:00:00 GMT RoanneLecky, KathrynChristie, PriyankShukla, Paula L.McClean, CatrionaKelly, Fri, 04 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101436 https://www.explorationpub.com/Journals/eemd/Article/101437 Circadian rhythms are present in almost every cell of the body and play important roles in various physiological processes. The central circadian clock in the suprachiasmatic nucleus (SCN) is synchronized to the environmental light-dark cycle and ensures a temporal order for the peripheral clocks, which in turn modulate tissue and organ function. This temporal organization is crucial for the precise timing of bodily processes, including sleep, glucocorticoid release, and the function of the glymphatic system. Sleep and the glymphatic system are significantly impacted by the rhythmic secretion of glucocorticoids. One important function of the glymphatic system is the clearance of waste metabolites, which most likely happens during sleep. Disruptions within the SCN, glucocorticoid rhythms, sleep, or glymphatic clearance have been implicated in compromised brain health. This review explores the current knowledge on the interdependence of the SCN, glucocorticoids, sleep, and the glymphatic system, and emphasizes their importance in homeostasis and pathology; in particular, Alzheimer’s disease. Review Wed, 16 Jul 2025 00:00:00 GMT Laura C. A.van der Zwet, StephanMichel, TomDeboer, Wed, 16 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101437 https://www.explorationpub.com/Journals/eemd/Article/101438 Background: Diabetes mellitus and vitamin D deficiency (VDD) are widespread global health concerns with overlapping metabolic risks. Emerging evidence suggests a bidirectional relationship: VDD exacerbates insulin resistance, whereas diabetes mellitus disrupts vitamin D metabolism. Methods: This meta-analysis was registered prospectively (PROSPERO CRD42025639951). We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library from their inception to January 2025 for observational studies examining the bidirectional associations between VDD and diabetes mellitus. Studies were eligible if they (1) employed cohort or case-control designs, (2) defined VDD as serum 25-hydroxyvitamin D [25(OH)D] < 20 ng/mL, and (3) diagnosed diabetes mellitus according to the American Diabetes Association (ADA) criteria. Two reviewers independently extracted data and assessed study quality using the Newcastle-Ottawa scale. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models (STATA 15.1 and RevMan 5.4). Results: Among 53 studies (n = 552,032), individuals with VDD had a 53% increased risk of developing type 2 diabetes mellitus (T2DM) (OR = 1.53, 95% CI: 1.38–1.70). Conversely, individuals with type 1 diabetes mellitus (T1DM) and T2DM had a 2.02-fold and 2.62-fold increased risk of VDD, respectively. Subgroup analyses demonstrated stronger associations in Asian populations (T1DM: OR = 2.21; Europe: OR = 1.65; P < 0.05 for regional difference) and among normal-weight T2DM patients (OR = 7.68, compared to obese: OR = 5.21). Discussion: This meta-analysis reveals a bidirectional link between VDD and diabetes mellitus, emphasizing subtype- and phenotype-specific risk profiles. Clinically, routine monitoring of serum 25(OH)D levels is recommended for diabetic patients, particularly in high-risk subgroups such as individuals with T1DM or lean T2DM phenotypes, and suggests targeted vitamin D supplementation for high-risk groups. On a public health scale, fortifying staple foods with vitamin D in regions with high deficiency rates, such as Asia, could alleviate the dual burden of VDD and diabetes mellitus. Meta-Analysis Fri, 18 Jul 2025 00:00:00 GMT HuilingHuang, ShaomeiShi, DongshengLi, Fri, 18 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101438 https://www.explorationpub.com/Journals/eemd/Article/101439 Background: Emerging evidence suggests that genetic variations in taste receptor genes may influence dietary behaviors, energy homeostasis, and metabolic risk, contributing to type 2 diabetes mellitus (T2DM) pathogenesis. The objective of this study is to evaluate the association between single nucleotide polymorphisms (SNPs) in taste receptor genes and T2DM. Methods: This systematic review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines and was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022351880). A comprehensive literature search was conducted across PubMed, ScienceDirect, Cochrane Library, and Google Scholar through June 2025. Original studies examining SNPs in taste receptor genes among individuals with T2DM were included. Quality assessment was performed independently by using the Newcastle-Ottawa scale. Results: Sixteen studies involving diverse populations met the inclusion criteria. Significant associations with T2DM were observed for SNPs in type 2 taste receptor gene family R member 3 (TAS2R3; rs11763979), TAS2R4 (rs2233998), TAS2R7, TAS2R9, TAS2R38, TAS2R50, cluster determinant 36 (CD36; rs1761667, rs3211956, rs7755), carbonic anhydrase VI gene (CA6; rs2274327), transient receptor potential vanilloid-1 (TRPV1; rs161364, rs8065080), transient receptor potential cation channel subfamily M gene member 5 (TRPM5; rs4929982), and TRPM8 (rs12472151). These polymorphisms may alter taste perception and gut hormone responses [e.g., glucagon-like peptide 1 (GLP-1)], affecting dietary intake, satiety, insulin secretion, and glucose regulation. Discussion: The findings suggest that genetic variations in taste receptor genes may contribute to T2DM through behavioral and metabolic mechanisms. Incorporating gustatory phenotyping with genotypic profiling could enable personalized dietary strategies and inform novel therapeutic approaches targeting taste-mediated gut signaling. Further large-scale, multi-ethnic, and mechanistic studies are warranted to confirm these associations and elucidate their clinical implications. Systematic Review Fri, 08 Aug 2025 00:00:00 GMT VishnuShivam, SahanaKannan, VishnuHarish, Fri, 08 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101439 https://www.explorationpub.com/Journals/eemd/Article/101446 Fatty liver, defined as lipid accumulation in more than 5% of hepatocytes, has become an increasingly important contributor to liver cirrhosis, particularly as viral hepatitis is being brought under control through vaccination and antiviral therapies. Abdominal obesity and insulin resistance play a central role in its pathogenesis. The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), continues to rise in parallel with the increasing prevalence of obesity and type 2 diabetes mellitus (T2DM). While meta-analyses indicate that the overall worldwide prevalence of MASLD is approximately 30%, higher rates have been reported in regions such as Latin America and North America. Among individuals with T2DM, the prevalence may reach up to 65%, and MASLD in these patients frequently progresses to metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis. Shared pathogenic mechanisms—most notably insulin resistance and chronic low-grade inflammation—drive disease progression, contributing to increased morbidity and mortality. The bidirectional relationship is further underscored by the observation that MASLD itself predisposes to the development of T2DM. In addition, the coexistence of MASLD and T2DM may exert a synergistic effect on cardiovascular disease (CVD) risk, and emerging evidence suggests that MASLD may represent an independent risk factor for CVD. Consequently, individuals with both MASLD and T2DM should be recognized as a particularly high-risk population requiring comprehensive monitoring of both hepatic and cardiovascular health. In this review, we aim to provide a concise overview of the etiopathogenesis, diagnostic approaches, and therapeutic strategies related to the MASLD-T2DM interface, a global health challenge that can be regarded as a pandemic of modern times. Review Mon, 10 Nov 2025 00:00:00 GMT Mehmet AliKosekli, Mon, 10 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101446 https://www.explorationpub.com/Journals/eemd/Article/101441 Aim: Baicalin and ginsenoside Rb1 show the ability to promote adipocyte browning, but their effects, especially combined treatment, and the related mechanisms under pathological conditions are less known. The study investigated the regulation of browning markers by baicalin and Rb1 under lipid overload and explored the potential implication of a serine/threonine protein kinase G protein-coupled receptor kinase 2 (GRK2). Methods: The 3T3-L1 cells under palmitic acid (PA) stimulation and male ICR mice on a high-fat diet (HFD) challenge were used to evaluate the effects of drugs. Results: GRK2 silencing and overexpression inversely regulated the protein abundance of PGC-1α and UCP-1 in 3T3-L1 adipocytes. Baicalin, Rb1, and their combination decreased the PA-induced elevation of GRK2 while increasing the thermogenetic markers at the protein and mRNA levels. In vivo, the tested drugs restored the expression of thermogenetic and mitochondrial biogenetic markers in the inguinal white adipose tissue (WAT) of HFD-fed mice. Consistently, the drug-treated mice displayed an improved metabolic profile. The baicalin-Rb1 combination showed a more potent effect in some examinations, and its effect was comparable to that of GRK2 inhibitor paroxetine or AMP-activated protein kinase activator metformin. Conclusions: Baicalin and Rb1, alone or in combination, improved the browning of adipocytes during differentiation and prevented the whitening shift of WAT on an HFD, which was associated with the downregulation of GRK2. The study expands the understanding of the anti-obesity effects of baicalin and Rb1 and the potential of Scutellariae Radix-Ginseng Radix et Rhizoma compatibility for treating obesity-associated metabolic diseases. Original Article Mon, 13 Oct 2025 00:00:00 GMT ZhuqiWang, JiayiLao, ZiqingWang, HongleiZhang, XinhongShi, KangLiu, Mon, 13 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101441 https://www.explorationpub.com/Journals/eemd/Article/101442 Background: Gestational diabetes mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, poses a significant and growing public health challenge in India. With India housing the world’s largest diabetes population, the rising prevalence of GDM has profound implications for maternal and neonatal health, contributing to complications including preeclampsia, macrosomia, neonatal hypoglycaemia, and increased lifelong risk of type 2 diabetes mellitus (T2DM) for both mother and child. Methods: We conducted a systematic literature search of PubMed, Embase, Google Scholar, and Cochrane Library for studies published between January 2019 and December 2024, with seminal works from 2015–2018. Search terms included “gestational diabetes mellitus”, “India”, “screening”, “prevalence”, “management”, and “health systems”. Eligible studies included peer-reviewed articles, government reports, and systematic reviews focusing on Indian populations. Two reviewers independently screened and extracted data. The PRISMA 2020 framework guided reporting. Results: From 2,847 initial records, 156 studies met the inclusion criteria. GDM prevalence in India ranges from 7.2% to 21.4%, with substantial regional variations. Southern states consistently report higher prevalence (15–22%) compared to northern (10–17%) and eastern regions (8–15%). Key challenges identified include low awareness among pregnant women (32% rural, 58% urban) and healthcare providers, inconsistent adoption of evidence-based guidelines (41% of facilities following standardized protocols), severe resource and infrastructural constraints, and significant socioeconomic barriers. Laboratory facilities for oral glucose tolerance test (OGTT) are available in only 34% of community health centers and 12% of primary health centers. Digital health interventions show promise but face implementation barriers, including limited smartphone penetration (45% in rural areas) and inadequate Accredited Social Health Activist (ASHA) workforce training (34% completion rate). Discussion: Despite the escalating burden of GDM in India, numerous unmet needs persist across the care continuum. This review proposes actionable recommendations, including simplified, cost-effective screening strategies, capacity building, integration into existing maternal health programs, and robust postpartum follow-up systems. Success requires sustained commitment to collaborative research, policy initiatives, and integrated, equitable, and sustainable GDM care approaches. Systematic Review Fri, 17 Oct 2025 00:00:00 GMT Sumedha RajendraZade, Sameer UttamraoKhasbage, AbhishekMishra, RekhaMehani, Fri, 17 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101442 https://www.explorationpub.com/Journals/eemd/Article/101443 Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist, showing a bidirectional relationship. MAFLD increases the risk of T2DM, while T2DM independently raises the likelihood of MAFLD. Methods: A comprehensive review was carried out on recent systematic reviews and meta-analyses by searching databases including PubMed, Embase, Web of Science, and the Cochrane database of systematic reviews, covering studies from inception to February 2025. Additionally, manual searches of reference lists were conducted. Inclusion criteria involved systematic reviews and meta-analyses of randomized controlled trials (RCTs) evaluating treatment effects on health outcomes in individuals with T2DM and MAFLD. Results: The search yielded 19 meta-analyses and 112 health outcomes from 622 unique articles. Most analyses focused on treatment effects on endocrine metabolic outcomes (n = 28), lipid metabolic indicators (n = 26), liver health indicators (n = 34), and body composition indicators (n = 24). High-quality evidence indicates that high-intensity interval training improves insulin resistance and low-density lipoprotein cholesterol levels. High-quality evidence also indicates sodium-glucose cotransporter-2 (SGLT-2) inhibitors improved liver proton density fat fraction and fatty liver index, while glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly liraglutide, enhanced subcutaneous adipose tissue (SAT). Moderate-quality evidence shows that dipeptidyl peptidase-4 (DPP-4) inhibitors enhanced insulin resistance and GLP-1RAs benefited triglycerides, aspartate transaminase, liver fat, and visceral adipose tissue. SGLT-2 inhibitors improved controlled attenuation parameter, body mass index (BMI), SAT, visceral fat mass, and moderate-intensity continuous training improved triglycerides and high-density lipoprotein cholesterol. Fifty-six outcomes were rated as low-quality evidence, and five as very low-quality. Discussion: GLP-1RAs, SGLT-2 inhibitors, DPP-4 inhibitors, exercise, and Chinese Herbal Medicines benefited liver health, glycemic control in T2DM with MAFLD, and impacted body composition and lipid metabolism. Systematic Review Thu, 23 Oct 2025 00:00:00 GMT HuilingHuang, ShaomeiShi, DongshengLi, Thu, 23 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101443 https://www.explorationpub.com/Journals/eemd/Article/101444 Type 2 diabetes mellitus (T2DM), expected to exceed 700 million cases by 2045, is usually attributed to obesity and peripheral resistance but neglects insulin’s structural integrity. This review introduces the Sulfur-Insulin Deformation Hypothesis, positing T2DM as a sulfur metabolism disorder where mitochondrial suffocation disrupts the transsulfuration pathway [methionine to cysteine via cystathionine β-synthase (CBS) and γ-lyase (CGL)], depleting cysteine and glutathione (GSH), impairing protein disulfide isomerase (PDI) activity, and deforming insulin’s disulfide bonds (A6–A11, A7–B7, A20–B19) as a primary trigger of insulin resistance. A literature synthesis was conducted (1995–2025) across PubMed, Scopus, Web of Science, and Google Scholar, using Medical Subject Headings (MeSH) terms like “sulfur metabolism”, “insulin misfolding”, and “mitochondrial dysfunction”. From 1,202 articles, 113 studies were selected, including in vitro insulin folding models, animal metabolic stress data, human sulfur biomarker analyses, and trials of sulfur donors (e.g., N-acetylcysteine). Mitochondrial dysfunction reduces adenosine triphosphate (ATP), depleting cysteine and GSH by 30–73.8% (red blood cell GSH: 1.78 ± 0.28 µmol/g vs. 6.75 ± 0.47 µmol/g Hb, P < 0.001), elevating reactive oxygen species (ROS). This impairs PDI isoforms (PDIA1, PDIA3, PDIA4), disrupting insulin bonds; the A6–A11 bond loses 50–70% affinity [r = –0.65, P < 0.05 for homeostatic model assessment of insulin resistance (HOMA-IR)], hindering phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signaling and glucose transporter type 4 (GLUT4) translocation. In 225 T2DM patients, PDIA4 elevation correlated with glucose (r = 0.62, P < 0.01) and reduced sensitivity (r = –0.67, P < 0.01). PDIA4 inhibition [presenilin 1 (PS1), IC50 = 4 μM] cuts ROS by 50% (P < 0.01), lowers hemoglobin A1c (HbA1c) by 1.2% (P < 0.05), and boosts β-cell survival by 30% (P < 0.05). Redox-mediated chain splitting degrades 20% of insulin (0.40 nmol/kg/min) at –137 mV, modulated by GSH. The hypothesis redefines T2DM as a sulfur-driven structural disorder, unveiling the gut-mitochondria-sulfur-insulin axis and advocating sulfur-centric therapies (e.g., N-acetylcysteine, methylsulfonylmethane). Review Mon, 03 Nov 2025 00:00:00 GMT Maher MonirAkl, AmrAhmed, Mon, 03 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101444 https://www.explorationpub.com/Journals/eemd/Article/101445 Adenylyl cyclase 5 knockout (AC5 KO) is a healthful longevity model; not only do the AC5 KO mice live a third longer than wild-type (WT) mice, but they are also protected against obesity, diabetes, heart failure, and exercise intolerance, mediated by anti-apoptosis, cell survival, myocardial biogenesis, and anti-oxidative stress mechanisms. To translate these salutary effects to the clinics, we developed a drug, C90, which recapitulates the AC5 KO model of healthful longevity. We then examined its effects on glucose tolerance and exercise capacity. C90 (30 mg/kg/day) or vehicle was chronically administered to age-matched C57BL/6 mice via an osmotic pump. The WT mice receiving C90 exhibited improved glucose tolerance, following glucose i.v. injection, when compared to the vehicle. Furthermore, the C90-treated mice had a lower fasting glucose level when compared to the vehicle-treated mice (113 ± 6.5 mg/dL vs. 129 ± 4.2 mg/dL, p < 0.05). Additionally, the WT group that received C90 exhibited greater exercise capacity, reflected by longer running distance (384 ± 27 m vs. 253 ± 16 m, p < 0.05) and greater work to exhaustion (18.1 ± 1.5 J vs. 12.4 ± 0.7 J, p < 0.05) than mice receiving vehicle. In view of these findings, C90 is an excellent candidate for clinical development as an effective pharmacological treatment for glucose intolerance and enhancing exercise performance. Short Communication Thu, 06 Nov 2025 00:00:00 GMT Dorothy E.Vatner, Claudio A.Bravo, MarkoOydanich, JieZhang, Jacques Y.Roberge, Stephen F.Vatner, Thu, 06 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101445 https://www.explorationpub.com/Journals/eemd/Article/101447 Hormonal dysregulation plays a central role in aging, exerting a profound, multidimensional impact on quality of life. This narrative review examines the impact of hormonal changes in understanding how age-dependent alterations in key hormonal axes, specifically those related to insulin, IGF-1, cortisol, thyroid hormones, parathyroid hormone, and sex hormones, affect metabolic, musculoskeletal, cognitive, and reproductive health. Altered hormone secretion and receptor sensitivity contribute to conditions such as type 2 diabetes mellitus, osteoporosis, sarcopenia, cognitive decline, and disrupted sleep patterns. Age-related shifts in thyroid and parathyroid function, including decreased T3 conversion and elevated PTH, further compound these physiological changes. These hormonal imbalances manifest as a multidimensional burden on quality of life, encompassing physical, cognitive, and psychosocial domains, which are particularly pronounced in postmenopausal women. Emerging therapies targeting GH secretion, myostatin inhibition, heat shock proteins, and IGF-1 offer promising avenues for mitigating age-associated symptoms and improving quality of life. Review Mon, 10 Nov 2025 00:00:00 GMT CarterCoggins, ShaanPatel, SankalpNigam, VikrantRai, Mon, 10 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101447 https://www.explorationpub.com/Journals/eemd/Article/101448 Aim: To investigate the natural history and progression of non-alcoholic fatty liver disease (NAFLD) in Chinese adults using a community-based longitudinal cohort. Methods: We analyzed data from 24,893 adults in the Beijing Health Management Cohort (2016–2021) with annual follow-up, including questionnaires, physical examinations, and laboratory tests. Participants were categorized into three states: healthy (S1, n = 17,906), NAFLD with body mass index (BMI) < 24 kg/m2 (S2, n = 1,139), and NAFLD with BMI ≥ 24 kg/m2 (S3, n = 5,848). Transition probabilities, mean sojourn times, and determinants of progression were estimated using a multi-state Markov model, with analyses stratified by sex. Results: Most individuals remained in their baseline state. Females in S1 were more likely to stay healthy than males (93.76% vs. 83.52%), while males had a higher risk of progression to S3 (12.59% vs. 4.23%). Females in S3 had a greater chance of reverting to S1 (21.33% vs. 18.18%). Mean sojourn time in S1 was longer for females (18.58 vs. 6.97 years), whereas males spent more time in S3 (5.37 vs. 4.18 years). Age, hyperuricemia, abdominal obesity, high triglycerides, and low high-density lipoprotein cholesterol (HDL-C) significantly increased the risk of progression. Conclusions: Sex differences strongly affect NAFLD progression in Chinese adults. Males are more likely to deteriorate, while females show higher recovery. Metabolic factors and obesity are key targets for early prevention and intervention. Original Article Thu, 13 Nov 2025 00:00:00 GMT JianminTang, HalengbiekeAheyeerke, ChaoTong, XuetongNi, TengruiCao, YumeiHan, ShuoChen, LinrunKong, XinghuaYang, Thu, 13 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101448 https://www.explorationpub.com/Journals/eemd/Article/101449 In this Commentary, we highlight the following issues concerning the development of increasingly more powerful incretin-based therapeutics (IBT) that to date have not been addressed with the attention they may deserve: 1. The appropriateness of BMI-based inclusion criteria for a drug capable of producing weight loss approaching that seen after bariatric surgery; 2. significant limitations inherent in communicating the results of an obesity trial involving a potent IBT; 3. the one-size-fits-all dosing strategies in trials may introduce new challenges for sponsors in the race to develop increasingly powerful IBT; 4. the currently imposed limitations on what can be communicated in the approved IBT product label create an advantageously unlevel playing field for opportunists such as compounding pharmacies. Proposals on how to address these issues are made in the text. While it is realized that the presented topics and solutions are not without controversy, they are intended to provoke further discussion. Commentary Fri, 14 Nov 2025 00:00:00 GMT Jerzy WKolaczynski, EvaSurmacz, Fri, 14 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101449 https://www.explorationpub.com/Journals/eemd/Article/101450 Psychiatric medication is vital in the treatment of a wide range of mental and behavioral health conditions, but has moderate metabolic consequences. The common side effects are weight gain, dyslipidemia, increased adiposity, elevated body mass index, increased insulin resistance, and metabolic alterations. Metabolic risk is lower with antidepressants than with antipsychotics. The side effects are linked to the metabolic syndrome, increasing the risk of heart disease, stroke, and type 2 diabetes. Cardiovascular diseases, dysglycemia and diabetes, atherogenic dyslipidemia, and metabolic syndrome are common complications associated with the use of antipsychotics. Therefore, it is essential to comprehend the metabolic alterations and develop strategies for early detection and intervention to mitigate these effects. This review discusses the metabolic alterations associated with common antipsychotic medications, followed by strategies to attenuate the effects. Review Mon, 24 Nov 2025 00:00:00 GMT MichaelNatalizio, SankalpNigam, VikrantRai, Mon, 24 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101450 https://www.explorationpub.com/Journals/eemd/Article/101451 The glucocorticoid receptor alpha (GRα) is traditionally viewed as a stress-response element with anti-inflammatory properties. Mechanistically, convergent evidence from global and tissue-specific knockout models, translational clinical studies, and evolutionary analyses indicates that GRα’s vital role in maintaining systemic homeostasis challenges its peripheral classification in clinical medicine. To reconceptualize GRα as a master regulator of organismal survival by analyzing its non-redundant, multisystemic functions and evaluating its relevance in health, development, and critical illness. This narrative synthesis combines structured searches performed using the Consensus AI research platform with evidence from genetic knockout models, tissue-specific deletion studies, and translational clinical research. Key findings are framed within comparative receptor analyses and integrated into broader physiological models of homeostasis and allostasis. Evolutionarily, global loss of GRα is perinatally lethal, characterized by failure of lung maturation and respiratory adaptation, accompanied by metabolic and neuroendocrine dysregulation. Tissue-specific deletions reveal essential roles in immune regulation, mitochondrial bioenergetics, cardiovascular function, and neuroendocrine stability. While several other receptors (including MR) are also essential for survival, GRα is distinctive for the breadth of cross-system coordination it provides. GRα exhibits both genomic and non-genomic actions that support rapid stress adaptation and promote restoration of systemic stability. Clinically, despite this broad integrative role, GRα’s survival-critical functions remain underrecognized in therapeutic strategies. Overall, the evidence supports GRα as a central integrator of postnatal survival, metabolic resilience, and immunological competence. GRα is a vital receptor whose systemic regulatory functions exceed its historical classification as a stress hormone mediator. Its role is not ancillary but foundational, anchoring survival across immune, metabolic, cardiovascular, and neuroendocrine systems. The collapse of this receptor’s function is not simply a component of disease—it is the tipping point that drives the organism from adaptation toward systemic breakdown. Recognizing GRα as a master survival receptor redefines therapeutic priorities, guiding biomarker-driven restoration of homeostasis in critical illness. Review Mon, 01 Dec 2025 00:00:00 GMT G. UmbertoMeduri, Mon, 01 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101451 https://www.explorationpub.com/Journals/eemd/Article/101452 Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) and dual incretin agonists have demonstrated significant potential in improving adipose tissue function beyond their established effects on appetite suppression and weight loss. These agents not only reduce overall fat mass but also induce favorable changes in fat distribution and adipose tissue quality. Notably, they enhance brown adipose tissue (BAT) activity and promote the browning of white adipose tissue (WAT), thereby increasing energy expenditure. They are associated with reductions in adipocyte size, particularly within visceral fat depots, alongside improvements in metabolic health markers. The aim of this publication is to provide a literature review on the effects of GLP-1RAs and dual incretin agonists on adipocyte type and size, adipose tissue functional remodeling, and their implications for obesity management. These findings highlight the capacity of incretin-based therapies to modulate adipose tissue biology, offering metabolic benefits that extend beyond weight reduction. Review Fri, 19 Dec 2025 00:00:00 GMT NinoTurashvili, Fri, 19 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101452 https://www.explorationpub.com/Journals/eemd/Article/101453 The global prevalence of obesity and type 2 diabetes mellitus (T2DM)—the most common metabolic disorders—has reached epidemic proportions over the past half-century, with obesity being a key driver of insulin resistance and T2DM development. These disorders are characterized by metaflammation (chronic low-grade inflammation across multiple metabolic organs like adipose tissue, liver, muscle, and the gut), which disrupts metabolic homeostasis, exacerbates insulin resistance, impairs insulin secretion, and links to other comorbidities such as cardiovascular diseases. A major advance in understanding inflammation resolution is the identification of specialized pro-resolving mediators (SPMs), a family of lipid mediators including resolvins, lipoxins, protectins, and maresins. Derived from polyunsaturated fatty acids (e.g., EPA, DHA), SPMs actively regulate inflammation resolution by constraining pro-inflammatory cell infiltration (e.g., neutrophils), promoting anti-inflammatory macrophage polarization (M2), enhancing efferocytosis (clearance of apoptotic cells), and preserving tissue barrier integrity—without inducing immunosuppression. This review summarizes evidence from human and animal studies on obesity-related metaflammation in metabolic tissues and the role of SPMs in resolving this inflammation. It details SPM mechanisms (e.g., maintaining adipose tissue homeostasis, improving insulin sensitivity, alleviating hepatic steatosis) and highlights their dysregulation in obesity (e.g., impaired biosynthesis, reduced receptor expression) as a critical driver of metabolic dysfunction. Finally, the review discusses the therapeutic potential of SPM-targeted strategies (e.g., ω-3 PUFA supplementation, SPM receptor activation) for alleviating obesity, T2DM, metabolic dysfunction-associated steatotic liver disease (MAFLD), and other metabolic disorders, along with future research directions in this field. Review Mon, 05 Jan 2026 00:00:00 GMT Ze-WeiZhao, Mon, 05 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101453 https://www.explorationpub.com/Journals/eemd/Article/101454 Endocrine hypertension (HT) includes a group of secondary hypertensive disorders caused by hormonal excess, primarily primary aldosteronism (PA), pheochromocytoma and paraganglioma (PPGL), and Cushing syndrome (CS). Although relatively uncommon, these conditions confer a disproportionately high cardiovascular risk that extends beyond blood pressure elevation. Aldosterone, catecholamines, and cortisol each induce myocardial fibrosis, oxidative stress, and endothelial dysfunction, leading to left ventricular hypertrophy (LVH), arrhythmias, and heart failure. In PA, chronic aldosterone excess activates mineralocorticoid receptors in cardiac and vascular tissues, promoting collagen deposition, diastolic dysfunction, and atrial fibrillation (AF) that may regress after adrenalectomy or pharmacologic blockade. PPGL causes episodic catecholamine surges resulting in β-adrenergic overstimulation, calcium overload, and microvascular ischemia, producing reversible or sometimes persistent catecholamine-induced cardiotoxicity. CS induces concentric hypertrophy, metabolic derangements, and vascular injury through prolonged glucocorticoid exposure, with cardiovascular recovery often incomplete after biochemical remission. Despite distinct hormonal origins, these disorders share convergent mechanisms, including fibroblast activation, mitochondrial injury, and maladaptive remodeling, that define endocrine cardiomyopathy. Early detection and targeted hormonal treatment can reverse much of the cardiac and vascular damage, whereas delayed recognition leads to irreversible fibrosis and persistent diastolic dysfunction. Recognition of these hormone-specific mechanisms is crucial for clinicians to anticipate, manage, and prevent these deleterious cardiovascular effects. Advances in molecular genetics, cardiac imaging, and biomarker research are improving our understanding of genotype-phenotype relationships and long-term reversibility of injury. Endocrine HT should therefore be recognized as a systemic cardiovascular disorder in which hormonal excess functions as a primary pathogenic driver; timely diagnosis and multidisciplinary care remain key to reducing morbidity and mortality. Review Thu, 08 Jan 2026 00:00:00 GMT Mehmet MuratŞahin, MacitKalçık, MucahitYetim, Muhammet CihatÇelik, LütfüBekar, YusufKaravelioğlu, Thu, 08 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101454 https://www.explorationpub.com/Journals/eemd/Article/101456 Osteoporosis is a disabling disease with a significant impact on the global population, particularly among older men and postmenopausal women. Several factors contribute to the increasing prevalence of osteoporosis, including greater life expectancy and the absence of symptoms in its early stages. The morbidity, mortality, and substantial economic burden associated with osteoporosis, especially due to hip fractures and related complications, constitute a major public health concern. Diagnosis should involve a comprehensive biochemical profile, along with additional tests to rule out secondary causes, which are often underdiagnosed and can influence the progression of the disease. Preventive measures and early diagnosis are essential to maintaining bone health and preventing fractures and disability. This review will focus on the definition, diagnostic approach, and key considerations prior to initiating treatment in patients with osteoporosis. Fracture risk prediction tools, including Fracture Risk Assessment Tool (FRAX), and treatment strategies are not addressed, as this review focuses on the appropriate diagnostic evaluation of osteoporosis and the systematic exclusion of secondary causes. Review Fri, 09 Jan 2026 00:00:00 GMT MaritzaVidal, Nancy E.Lane, Fri, 09 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101456 https://www.explorationpub.com/Journals/eemd/Article/101455 Background: Metabolic syndrome and dyslipidaemia increase the risk of death by two or three times. In this context, the role of apolipoprotein A-I (Apo A-I), the main structural protein of high-density lipoprotein (HDL), stands out, since its anti-inflammatory potential reduces cardiovascular risk. Further, genetic modifications, such as the rs670 single-nucleotide polymorphism (SNP), in the promoter region of the APOA1 gene are associated with the development of cardiovascular events, dyslipidemia, and diabetes, as well as metabolic syndrome. Thus, this study aims to investigate the relation between the occurrence of dyslipidemia and the rs670 SNP genotypes. Methods: An integrative and systematic review was performed with the LitVar2 database according to the PRISMA protocol standards. Studies were researched up to August 2025. Then, a meta-analysis was performed using the fixed-effects model, since the study was considered homogeneous based on the I2 value (< 50%). Results: Of the 99 found articles in the database, 5 referred to metabolic disorders (n = 7,705—4 Chinese studies and 1 Iranian study) and were published between 2015 and 2018. Three (n = 2,784 patients or 36.13%) of the articles indicated an association between the polymorphic allele and a higher risk of developing dyslipidemia with a relative risk of 1.16 (IC 95% 1.09–1.23, p < 0.01, I2 = 0%). Relative risk (IC 95%) was presented, and p < 0.05 was defined as the significance criterion. Discussion: This study reinforces a possible association between the influence of SNP rs670 and dyslipidemia. This emphasizes the importance of conducting further research incorporating a larger and more diverse study group, as well as investigating the genetic and environmental influence on the phenotypic expression of the rs670 SNP. Meta-Analysis Fri, 09 Jan 2026 00:00:00 GMT Cauan FariasAnanias, Mateus OliveiraFernandes, Antônia Gabriellade Souza Freitas, Sarah Maria GuilhermeOliveira, Lais MaurícioKfuri, Emanuel PaulaMagalhães, Glautemberg de AlmeidaViana, Bruna RibeiroDuque, Izabell Maria MartinsTeixeira, Natasha Maria LimaPinheiro, Mac Dionys Rodrigues daCosta, Ramon Róseo Paula Pessoa Bezerra deMenezes, Tiago LimaSampaio, Fri, 09 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101455 https://www.explorationpub.com/Journals/eemd/Article/101457 A pro-inflammatory state with elevated cytokines influenced by both environmental and genetic factors is a key characteristic of both type 1 diabetes (T1DM) and type 2 diabetes (T2DM). Cytokines promote immune cell infiltration and degradation of the pancreatic islets, which play a direct role in the development of insulin resistance in T1DM. Cytokines also interfere with insulin signaling pathways and lead to metabolic dysfunction, contributing to the development of insulin resistance in patients with T2DM. In this narrative review, we have discussed the mechanisms of action and specific effects on insulin resistance of different cytokines, the influence of single-nucleotide polymorphisms and genetic factors that alter cytokine levels, and the development of insulin resistance. Further, we have discussed the complication of diabetes with a focus on diabetic foot ulcers, wounds, impaired wound healing, and reduced angiogenesis in association with the role of cytokines. Finally, the discussion addresses interventions for managing cytokines, such as Treg-based therapies, along with the various challenges presented by therapies targeting cytokine dysregulation and their effects on insulin resistance. Review Wed, 21 Jan 2026 00:00:00 GMT ArbabAlam, SukhjinderMomi, HaroonRiyaz, OdetBehado, VikrantRai, Wed, 21 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101457 https://www.explorationpub.com/Journals/eemd/Article/101458 This commentary discusses a recent article (J Diabetes 2025;17(3):e70063), focusing on interpreting the study’s sex-stratified results in a broader clinical and mechanistic context. The authors of this systematic review and meta-analysis of 14 randomized trials demonstrate that women achieve greater weight loss induced by glucagon-like peptide-1 (GLP-1) receptor agonists compared to men (mean difference of 1.04 kg or 1.69%). Analyses specific to different drugs consistently show that women benefit more from dulaglutide, liraglutide, semaglutide, and retatrutide, with trials focused on obesity further emphasizing this gap. Sensitivity analyses confirm the reliability of these findings and indicate the absence of publication bias. We discuss the clinical implications of these results, suggesting that healthcare providers should consider sex differences when counseling, monitoring, and dosing patients. We also advocate for future trials that are adequately powered and stratified by sex to evaluate factors such as adherence, adverse events, and body composition. Mechanistic hypotheses, such as sex-related pharmacokinetics, estrogen-GLP-1 synergy, and varying inflammatory responses, should be investigated further to inform precision dosing. Lastly, we recommend that regulatory agencies revisit current labeling, which claims no sex differences, as more sex-stratified evidence becomes available. It is important to acknowledge the existing heterogeneity and remaining uncertainties in this area of research. Commentary Mon, 02 Feb 2026 00:00:00 GMT RalfWeiskirchen, AmedeoLonardo, Mon, 02 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101458 https://www.explorationpub.com/Journals/eemd/Article/101459 Aim: Hypertriglyceridemia is linked to increased risk of diabetes diagnosis, incidence, and mortality. However, whether individuals with normal triglyceride levels (i.e., < 1.7 mmol/L) uniformly exhibit low diabetes risk remains underexplored. Specifically, it is unclear whether triglyceride levels within the normal range are associated with plasma glucose levels and the prevalence of type 2 diabetes (T2DM). This study aimed to address these gaps by examining the associations between triglyceride levels and fasting plasma glucose, as well as between triglyceride levels and T2DM, in individuals with triglycerides in the normal range. Methods: This cross-sectional study included 16,706 Chinese adults with triglyceride levels below 1.7 mmol/L. Among them, 1,067 had T2DM. Associations between triglyceride levels and fasting plasma glucose were assessed using linear regression, while associations with T2DM were evaluated using binary logistic regression. The optimal triglyceride cut-off for T2DM diagnosis was determined via receiver operating characteristic (ROC) curve analysis. Results: Triglyceride levels were positively associated with fasting plasma glucose after multivariate adjustment (β = 0.034, P < 0.001). A one-unit increase in the natural log of triglyceride levels was associated with a 61% higher adjusted odds of T2DM [odds ratio (OR), 1.61; 95% confidence interval (CI), 1.19–2.17; P = 0.002]. The optimal triglyceride cut-off for T2DM diagnosis was 1.09 mmol/L. Participants with triglyceride levels ≥ 1.09 mmol/L had a 28% higher odds of T2DM (OR, 1.28; 95% CI, 1.07–1.53; P = 0.006) compared to those with levels below the cut-off. Conclusions: Among individuals with normal triglyceride levels, higher triglyceride concentrations were associated with higher odds of T2DM diagnosis, with an optimal diagnostic cut-off of 1.09 mmol/L. These findings suggest that adults with triglyceride levels more than 1.09 mmol/L may benefit from closer monitoring for T2DM development. Original Article Thu, 12 Feb 2026 00:00:00 GMT YutangWang, HongyingLiu, ShenzhouMa, TingtingQian, HuiSun, QunXu, XujuanHou, WenqiHu, GuangZhang, MariaJelinic, YanFang, DavidSong, GuangYang, Thu, 12 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101459 https://www.explorationpub.com/Journals/eemd/Article/101460 The dominant paradigm for healthy ageing in women+ (all genders) focuses on estrogen and sees the menopause, per se, as a major health problem (with low estrogen and progesterone levels). In reality, the risks for diseases that increase at older ages originate during the menstruating years. Rarely discussed evidence supports the central role of progesterone and normally ovulatory menstrual cycles in preventing early cardiovascular disease, fragility fractures, dementia, and cancers. Menstrual cycles with normal and predictable lengths but disturbed ovulation, including short luteal phases with lower progesterone production as well as anovulation without progesterone, likely occur in over 25% of all such cycles. These Subclinical Ovulatory Disturbances are usually an adaptive and protective response to physiological, sociocultural, or emotional stressors. Ovulatory disturbances and risks for health issues during ageing are intrinsically related to the social determinants of health—wholesome food, plentiful physical activity, strong communities, and access to timely and appropriate medical care. This review discusses the empirical evidence that normal ovulation and progesterone production during the premenopausal years lead to the prevention of early heart attacks and fragility fractures. Few studies document the effects of prevalent Subclinical Ovulatory Disturbances on brain issues (sleep, night sweats, ischemic strokes, pain, and addictions) and cancer risks. Serious gaps in women+’s fundamental reproductive physiology must be addressed with unbiased (population-based), rigorously collected longitudinal physiological, hormonal, and sociocultural data. Progesterone therapy during perimenopause and menopause also indirectly leads to healthy ageing through effective treatment of night sweats, hot flushes, and disturbed sleep, which are associated with cardiovascular problems and osteoporosis. Not only is progesterone effective for vasomotor symptoms in menopause, but also effective in perimenopause, a time of high and chaotic estrogen levels. In sum, strong summarized evidence suggests that progesterone and ovulation need further exploration for their important roles in promoting healthy ageing for women+. Review Thu, 26 Feb 2026 00:00:00 GMT Jerilynn C.Prior, Virginia J.Vitzthum, Thu, 26 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101460 https://www.explorationpub.com/Journals/eemd/Article/101461 Diabetes and metabolic dysfunction represent growing global health challenges, and current therapies mitigate hyperglycemia without sufficiently altering the underlying disease processes. Rapid advances in regenerative medicine, gene editing, and nano-enabled drug delivery are reshaping therapeutic possibilities, offering the potential to restore β-cell function, enhance insulin sensitivity, and personalize care at an unprecedented scale. This review synthesizes emerging therapeutic strategies with the greatest translational promise, including stem cell-derived islet replacement, immune-evasive encapsulation devices, CRISPR-based gene correction, and targeted or glucose-responsive nanocarriers engineered for noninvasive insulin delivery. Complementary advances in multi-omics profiling, proteogenomics, microbiome science, and artificial intelligence are enabling stratification of patients based on molecular signatures, optimizing therapeutic selection, and predicting clinical outcomes. Despite remarkable breakthroughs—such as the early-phase clinical success of stem cell-derived β-cell replacement and organ-targeted lipid nanoparticles (LNPs)—significant barriers remain, including immunogenicity, off-target editing, scalability, ethical concerns, and long-term safety. By integrating mechanistic insights with translational developments, this review outlines a forward-looking perspective on next-generation treatments poised to shift diabetes care from glycemic management toward disease modification and personalized metabolic restoration. Review Mon, 09 Mar 2026 00:00:00 GMT Maria-KalliopiSpanorriga, ChristosFragoulis, IriniBega, KyriakiMavromoustakou, IoannisGatsouniotis, Stavroula-PanagiotaLontou, KyriakosDimitriadis, KonstantinosAznaouridis, NikolaosKtenopoulos, AnastasiaThanopoulou, ChristinaChrysohoou, KonstantinosTsioufis, Mon, 09 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101461 https://www.explorationpub.com/Journals/eemd/Article/101462 Aim: In Mexico, 18.3% of patients over 20 years of age suffer from type 2 diabetes mellitus (T2DM). Visceral fat has been identified as a risk factor for developing T2DM, considering that its effect depends mainly on the amount, it has been proposed that its location also participates in the genesis of T2DM. This paper aims to analyze whether the location of fatty depots participates in the appearance of T2DM in patients with metabolic syndrome. Methods: A total of 101 patients with metabolic syndrome according to the criteria of the International Diabetes Federation were included. In all of them, epicardial fat (EF) was measured by echocardiography, according to the Iacobelis criteria. Preperitoneal fat (PreF), mesenteric fat (MF), and perirenal fat (PF) were also measured by ultrasound. The statistical methods used were the odds ratio (OR) and Fisher’s exact test. Results: We found a significant association between EF thickness (OR 8.28, 95% CI 2.16–31.70, p = 0.001) and MF (OR 4.27, 95% CI 1.63–11.13, p = 0.0037) with T2DM, 60% of patients with increased PF presented T2DM. Interestingly, no patient with a PF less than 10 mm presented with T2DM. We found no association between PreF and T2DM (OR 0.88, 95% CI 0.32–2.40). Conclusions: The results suggest that the location of adipose tissue plays an important role in the development of T2DM. This may be due to the type of adipocytokines secreted by the various fat deposits and their metabolic effects. Original Article Tue, 10 Mar 2026 00:00:00 GMT Ivonne G.Narváez-Ortiz, Jorge L.Narváez-Rivera, Daniel R.Benítez-Maldonado, Alberto F.Rubio-Guerra, CarolinaGuerrero-García, AlbertoMaceda-Serrano, Tue, 10 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101462 https://www.explorationpub.com/Journals/eemd/Article/101463 Aim: Necrotizing fasciitis (NF) is a severe and early challenging-to-identify complication of diabetic foot (DF). This study aimed to develop and validate a novel risk assessment model for NF with DF patients utilizing conventional clinical indicators. Methods: A retrospective analysis was conducted on 815 DF patients admitted to the First Affiliated Hospital of Chongqing Medical University between October 2018 and April 2022. Based on the presence of NF, patients were stratified into a DF group (n = 703) and a DF complicated with NF (DNF) group (n = 112). Clinically and statistically significant variables were converted into categorical form. A new risk assessment for DNF (NRADNF) nomogram was developed via multivariable stepwise logistic regression. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) for discriminative ability, the Hosmer-Lemeshow goodness-of-fit test for calibration, decision curve analysis (DCA) for clinical utility, and bootstrap resampling for stability. Results: The final NRADNF model incorporated six indicators: age < 60 years, body temperature ≥ 38°C, foot skin necrosis, neutrophil-to-lymphocyte ratio (NLR) ≥ 8.5, hypersensitive C-reactive protein > 20 mg/L, and hemoglobin ≤ 100 g/L. The model demonstrated favorable predictive performance with an AUC of 0.815 (95% CI: 0.773, 0.857), and it was significantly superior to the RADNF model by our team (P = 0.027). Calibration curves and the Hosmer-Lemeshow test indicated good accuracy. DCA confirmed the model’s clinical net benefit, and internal validation via bootstrap resampling supported its stability. Conclusions: Based on its favorable predictive performance and accessible indicators, the NRADNF model is suitable for preliminary screening of DNF in clinical practice. Original Article Thu, 12 Mar 2026 00:00:00 GMT XunLi, XiaoruZhang, ChaoCheng, XiaNi, QiuhongHuang, ZiweiTang, WenruiZhao, ZhipengDu, QinglianZeng, QingfengCheng, Thu, 12 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101463 https://www.explorationpub.com/Journals/eemd/Article/101464 The hypothesis that early-life antibiotic exposure predisposes to obesity has, over the past decade, gained substantial traction across both biomedical literature and public discourse. Its appeal lies in a seemingly coherent mechanistic framework: disruption of the developing intestinal microbiota is presumed to induce long-lasting alterations in metabolic homeostasis, thereby promoting increased adiposity. However, reported effect sizes are consistently modest, with odds ratios typically ranging from 1.1 to 1.3, values that approach the limits of residual confounding and statistical imprecision. Studies incorporating rigorous adjustment for familial environment, socioeconomic status, and dietary patterns observe a complete loss of the association, underscoring the dominant influence of these confounders. This review revisits the conceptual emergence and sustained prominence of the antibiotic-obesity paradigm, positioning it as a case study in the amplification of weak epidemiological signals through mechanistic plausibility. Notwithstanding its methodological limitations, the hypothesis has exerted a constructive influence by fostering more judicious antibiotic use and stimulating renewed investigation into host-microbiota interactions within the context of metabolic disease. Review Thu, 19 Mar 2026 00:00:00 GMT ValérieLannoy, Thu, 19 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101464 https://www.explorationpub.com/Journals/eemd/Article/101465 Epiploic appendagitis is a rare, self-limiting inflammatory condition of the colonic epiploic appendages. It commonly presents with acute focal lower quadrant abdominal pain and may mimic appendicitis, colitis, or diverticulitis. Rapid weight loss has been proposed as a potential predisposing factor, although clinical evidence remains limited. This report describes a case of epiploic appendagitis occurring in temporal association with substantial and relatively rapid weight reduction during treatment with tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. A 45-year-old individual with a history of obesity, prediabetes, hypertension, hypothyroidism, and inflammatory bowel syndrome presented to primary care with right lower quadrant abdominal pain. Initial evaluation attributed symptoms to constipation; however, pain progressed despite management. Computed tomography (CT) of the abdomen and pelvis with contrast was obtained due to concern for appendicitis and demonstrated imaging findings consistent with epiploic appendagitis localized to the cecum. The patient had experienced clinically significant and relatively rapid weight loss during tirzepatide dose escalation prior to presentation. Management was conservative with nonsteroidal anti-inflammatory drugs and supportive care, without surgical intervention. Symptoms resolved completely within two weeks, and tirzepatide therapy was continued without recurrence. Although epiploic appendagitis has not been identified as a safety signal in randomized trials, systematic reviews, or pharmacovigilance analyses of GLP-1/GIP receptor agonists, this case highlights epiploic appendagitis as an important diagnostic consideration in patients presenting with focal abdominal pain during periods of substantial weight loss. Awareness of this uncommon condition may help prevent misdiagnosis and unnecessary interventions as pharmacologic weight loss therapies become more widely used. Case Report Thu, 02 Apr 2026 00:00:00 GMT Beshoy M.Astfanous, Jennifer D.Goldman, Thu, 02 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101465 https://www.explorationpub.com/Journals/eemd/Article/101466 Osteoarthritis (OA) is the most prevalent form of arthritis and a leading cause of disability worldwide. Epidemiological studies indicate that its global prevalence is rising, particularly among women, who often experience more severe disease than men. This sex disparity is most pronounced around menopause and is influenced by female-specific biological and hormonal factors, joint morphology, reproductive history, and sex-specific comorbidities that contribute to disease onset and progression. A mechanistic understanding of these factors is essential to identify individuals at risk, implement preventive strategies, enable early diagnosis, and mitigate complications, ultimately preserving function and quality of life. This review focuses on the determinants underlying the higher incidence and severity of OA in women, highlighting the interplay between hormonal changes, anatomy, and systemic factors. Review Fri, 10 Apr 2026 00:00:00 GMT MaritzaVidal, Nancy ELane, Fri, 10 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eemd/Article/101466