Background: Type 1 diabetes (T1D) is increasingly recognized as a condition associated with impaired skeletal health and increased fracture risk. Although osteoporosis is usually considered more clinically relevant after menopause, diabetes-related skeletal alterations may begin earlier in life. This scoping review aimed to map the available evidence on bone-health outcomes in premenopausal women with T1D. Methods: A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). PubMed/MEDLINE, Scopus, Web of Science, CINAHL and the Cochrane Library were searched, supplemented by Google Scholar and manual screening of reference lists. Eligible studies examined bone mineral density (BMD), fracture history or fracture risk, bone turnover markers, quantitative ultrasound parameters, bone microarchitecture, or other skeletal outcomes in premenopausal women or women with T1D. Results: Seven studies met the eligibility criteria. The included studies were mainly observational and varied in sample size, age range, diabetes duration, skeletal sites assessed, and bone-assessment methods. Most studies reported lower BMD or less favorable skeletal parameters in premenopausal women with T1D compared with women without diabetes, particularly at peripheral or hip-related skeletal sites. Quantitative ultrasound studies suggested impaired peripheral skeletal properties, while one MRI-based study identified trabecular microarchitectural deficits. Several studies also reported altered bone turnover markers and associations between poorer glycemic control, adverse health behaviors or diabetes-related complications, and poorer bone outcomes. Fracture data were limited and were based on previous or self-reported fractures. Potential determinants of skeletal health were variably reported across studies, with more consistent consideration of body mass index and selected lifestyle or reproductive factors than of autoimmune, nutritional, medication-related, and detailed reproductive variables. Conclusions: Available evidence indicates that premenopausal women with T1D may exhibit early alterations in skeletal health, including differences in BMD, peripheral bone measures, bone turnover, and microarchitecture. These findings highlight the potential importance of considering bone health before the menopausal transition. However, prospective data on fragility fractures remain limited, and further longitudinal studies incorporating detailed reproductive, metabolic, and clinical factors are needed to clarify the long-term skeletal implications and inform future risk-assessment strategies.

Background/Objectives: Type 2 diabetes mellitus (T2DM) has a growing prevalence, even in developed countries. Because of the increase in life expectancy, the number of older people with T2DM is also increasing. The management and handling of these patients is challenging due to its co-morbidities. Aim: In the present study, we reviewed the literature in order to investigate the impact of sodium–glucose co-transporter 2 inhibitors (SGLT-2 inhibitors) on bone metabolism and fracture incidence. Methods: We searched the literature using the databases of PubMed, CENTRAL and Cochrane Central Register of Controlled Trials up to December 2024. Results: There is a controversial position in the literature concerning the effects of SGLT2 inhibitors when administered in T2DM, with respect to bone metabolism and bone fracture incidence. Multiple studies suggest the SGLT2 inhibitors have a disadvantageous effect on bone metabolism and fracture incidence, while several others suggest a beneficial effect. Conclusions: Patients with type 2 diabetes mellitus are at high risk of alterations in their bone metabolism. SGLT2 inhibitors are a novel class with pleiotropic effects in many organs, such as the kidneys and heart, although their effect on bone metabolism and fracture incidence is still unclear. Until we have more clinical data, all caregivers (medical and nursing staff) should be aware of possible bone fractures in patients receiving this class of agents.

Gestational diabetes mellitus (GDM) is an important health issue, as it is connected with adverse effects to the mother as well as the fetus. A factor of essence for the pathology of this disorder is the gut microbiota, which seems to have an impact on the development and course of GDM. The role of the gut microbiota on maternal reproductive health and all the changes that happen during pregnancy as well as during the neonatal period is of high interest. The correct establishment and maturation of the gut microbiota is of high importance for the development of basic biological systems. The aim of this study is to provide a systematic review of the literature on the effect of GDM on the gut microbiota of neonates, as well as possible links to morbidity and mortality of neonates born to mothers with GDM. Systematic research took place in databases including PubMed and Scopus until June 2024. Data that involved demographics, methodology, and changes to the microbiota were derived and divided based on patients with exposure to or with GDM. The research conducted on online databases revealed 316 studies, of which only 16 met all the criteria and were included in this review. Research from the studies showed great heterogeneity and varying findings at the level of changes in α and β diversity and enrichment or depletion in phylum, gene, species, and operational taxonomic units in the neonatal gut microbiota of infants born to mothers with GDM. The ways in which the microbiota of neonates and infants are altered due to GDM remain largely unclear and require further investigation. Future studies are needed to explore and clarify these mechanisms.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Diabetes mellitus (DM) has a growing prevalence worldwide, even in developing countries. Many antidiabetic agents are used to improve glycemic control; however, in cases of an insufficient outcome, insulin is administered. Yet, the timing of proper insulin administration is still a subject of intense research. To date, there have been no recommendations or guidelines for the use of continuous subcutaneous insulin infusion (CSII) in Type 2 Diabetes Mellitus (T2DM). In the present study, we have performed a meta-analysis to evaluate the use of CSII in patients with T2DM. An extensive literature search was conducted through the electronic databases Pubmed, Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) from October 2019–May 2022, for interventional studies related to T2DMI and CSII versus multiple daily injections (MDI). We included articles published in the English language only, yielding a total of thirteen studies. We found better outcomes in patients receiving CSII, in regard to glycated hemoglobin (HbA1c) and total insulin dose. In contrast, fasting plasma glucose and body weight did not show statistically significant differences between the two groups. Our analyses showed that CSII could be beneficial in patients with T2DM in order to achieve their glucose targets.

Background and Objectives: The association between diabetes mellitus and increased risk of bone fractures has led to the investigation of the impact of antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP1RAs) are a relatively novel and promising class of anti-hyperglycemic drugs. In addition to their blood glucose lowering action, GLP1RAs seem to have additional pleiotropic properties such as a beneficial skeletal effect; although the underlying mechanisms are not completely understood. The present systematic review summarizes current evidence about GLP1RAs and their effects on bone metabolism and fracture. Methods: An extensive literature search was conducted based on electronic databases namely, PubMed, Google Scholar and Cochrane Central Register of Controlled Trials (CENTRAL) through October 2019 to January 2020 for articles related to bone mineral density, diabetes mellitus and GLP1RAs. We included articles published in English. Finally, we included four randomized controlled trials, three meta-analyses, a case-control study and a population-based cohort analysis. Results: Based on the articles included, the animal studies indicated the salutary skeletal effects of GLP1RAs in opposition to what has been commonly observed in human studies, showing that these agents have no impact on bone mineral density (BMD) and the turnover markers. Moreover, it was demonstrated that GLP1 was not associated with fracture risk as compared to other anti-hyperglycemic drugs. Conclusions: Findings from this systematic review have demonstrated the neutral impact of GLP1RAs on BMD. Moreover, further double-blind randomized controlled trials are needed to draw more meaningful and significant conclusions on the efficacy of GLP1RAs on BMD.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Thalassemia major (TM) is a hereditary disease caused by defective globin synthesis. Because of the significant increase in life expectancy, these patients are suffering from various health conditions, including endocrinopathies and low bone mineral density. The aim of the present study was to investigate the correlation between clinical and biochemical parameters as well as to identify possible relations in a genotype to phenotype pattern. Sixty-four patients with TM (32 men and 32 women) participated in a cross-sectional study design. The patients were recruited from "Aghia Sofia" Children's Hospital. Clinical and biochemical parameters were evaluated as well as specific mutations were identified. We have found significant correlations between biochemical parameters and iron chelation, hormone replacement treatment as well as TM genotype and hematocrit and T-score. To conclude, the current study showed that clinical parameters of TM patients correlate significantly with both biochemical factors and genotypical patient parameters. Our present study showed that there is a connection between genotype and phenotype as, for example, the identified relation between hematocrit and T-scores and TM-specific mutations. This connection indicates that there is still much more to learn about the role of mutations not only in the disease itself but also in the underlying comorbidities.

Acute lymphoblastic leukemia is the most common childhood malignancy. Rhabdomyosarcoma, on the other hand, is a rare type of malignancy which belongs to the primitive neuroectodermal family of tumors. The aim of the present study was to use computational methods in order to examine the similarities and differences of the two different tumors using two cell lines as a model, the T-cell acute lymphoblastic leukemia CCRF-CEM and rhabdomyosarcoma TE-671, and, in particular, similarities of the metabolic pathways utilized by two different cell types in vitro. Both cell lines were studied using microarray technology. Differential expression profile has revealed genes with similar expression, suggesting that there are common mechanisms between the two cell types, where some of these mechanisms are preserved from their ancestor embryonic cells. Expression of identified species was modeled using known functions, in order to find common patterns in metabolism-related mechanisms. Species expression manifested very interesting dynamics, and we were able to model the system with elliptical/helical functions. We discuss the results of our analysis in the context of the commonly occurring genes between the two cell lines and the respective participating pathways as far as extracellular signaling and cell cycle regulation/proliferation are concerned. In the present study, we have developed a methodology, which was able to unravel some of the underlying dynamics of the metabolism-related species of two different cell types. Such approaches could prove useful in understanding the mechanisms of tumor ontogenesis, progression, and proliferation.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Glucocorticoids (GCs) are still first-line drugs for the treatment of childhood acute lymphoblastic leukemia (ALL). Prednisolone is a corticosteroid and one of the most important agents in the treatment of ALL. We report here a study of Prednisolone treatment using as a model a leukemia cell line with subsequent investigation of resistance-related gene expression. Gene silencing has been used in order to identify significant targets of resistance to GC-induced apoptosis in ALL cells. We analyzed effects of increasing doses of Prednisolone on ALL cell survival and growth, and we monitored immediate effects on gene expression through gene expression assays. We determined Prednisolone cytotoxicity and cell cycle distribution as well as DNA content. Upon treatment with escalating Prednisolone concentration, we observed a gradual decline in cell survival. MCL1 and GRIM19 were investigated as possible genes for the intrinsic capacity of this cell line to respond to corticosteroid and a snapshot of early changes was examined. Early MCL1 and GRIM19 expression correlated significantly to late GC-induced apoptosis. Prednisolone competitively induces MCL1 expression. Consistently with previous studies on primary leukemia blasts, cells are sensitive to proteasome inhibitor MG132; no interference of Prednisolone with MG132 effects on this cell line was noted. The inherent plasticity of clinically evolving cancer justifies approaches to characterize and prevent undesirable activation of early oncogenic pathways. Study of the pattern of intracellular signal pathway activation by anticancer drugs can lead to development of efficient treatment strategies by reducing detrimental secondary effects.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. It is known that deregulation of adipokine pathways is probably implicated in the ontogenesis of ALL. The present work aims at investigating the role of adiponectin and its effects on an ALL cell line. The CCRF-CEM cells were used as a model. Cells have been treated with adiponectin, with different concentrations up to 72 h. Cytotoxicity and cell cycle distribution were investigated for all concentrations using flow cytometry. Selected concentrations were also used for additional microarray analysis, using a small gene set of cancer-related genes. Lower and higher adiponectin concentrations did not produce an inhibition of proliferation, as well as an increase in cell death. It was found that adiponectin regulated differentially genes, such as CD22, CDH1, IFNG, LCK, MSH2, SPINT2, and others. At the same time, it appeared that adiponectin-related gene expression was more active on chromosomes 18 and 1. Machine learning classification algorithms showed that several genes were grouped together indicating common regulatory mechanisms. The present study showed that adiponectin is able to induce gene differential expression in leukemic cells in vitro, suggesting a possible role in the progression of leukemia. It is also an indication that more studies are required in order to further understand the role of adiponectin and adipokines in general in the role of human neoplasms.

Thalassemia Major (TM) is a hereditary disease caused by defective globin synthesis. Because of the significant increase in life expectancy, these patients suffer from various health conditions, including endocrinopathies and low bone mineral density. Aim: The aim of the present study was to evaluate the fracture incidence regarding the markers of bone metabolism, bone mineral density and treatment of osteoporosis as well as treatment of comorbidities. Methods: Sixty-four patients with TM (32 men and 32 women) participated in a cross-sectional study design. The patients were recruited from “Aghia Sofia” Children’s Hospital and evaluated using dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck and with markers of bone remodeling including receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide (CTX), and sclerostin. Results: The statistical analysis of markers of bone metabolism in relation to fractures revealed no statistical significance. However, statistical analysis of bone mineral density and markers of bone metabolism in relation to fractures was also not significant. Conclusions: In TM patients, fractures are not related to bone mineral density. Maybe some other conditions are the cause, haemosidirosis, drugs, comorbid conditions.