Abstract: Bioidentical hormone replacement therapy (BHRT) traditionally operates within a triad consisting of sex hormones, thyroid hormones, and adrenal glucocorticoids. Despite widespread adoption, a substantial proportion of patients experience persistent dysglycemia, adrenal instability, fluctuations in symptom control, and inconsistent responses to therapy even when laboratory values appear biochemically normalized. These clinical patterns suggest that an essential regulatory element is missing from the current BHRT conceptual model.This narrative review proposes the Insulin–Cortisol–Vitamin C (ICV) Axis as a previously unrecognized hormonal network central to metabolic and endocrine homeostasis. Insulin profoundly influences sex-hormone binding globulin (SHBG), estradiol and testosterone bioavailability, progesterone responsiveness, thyroid hormone conversion, mitochondrial ATP production, and cortisol reactivity—yet insulin is rarely evaluated in BHRT. Cortisol, in turn, directly modulates insulin sensitivity and metabolic function, while vitamin C is required for cortisol synthesis, adrenal recovery, endothelial nitric oxide signaling, mitochondrial redox regulation, and antioxidant defense. Together, disturbances in these three components can generate characteristic clinical presentations frequently encountered in BHRT practice.In parallel, emerging evidence—including metabolic insights from GLP-1 receptor agonist therapy—indicates that vitamin C status and oxidative stress modulation play broader roles in insulin sensitivity and hormonal signaling than previously recognized. Integrating these findings, the ICV Axis provides a systems-level framework capable of explaining BHRT treatment failures, variable patient responses, and persistent symptomatology despite standard hormone optimization.The purpose of this review is to synthesize biochemical, endocrine, and nutritional evidence supporting this new axis, and to outline a clinically actionable update to BHRT incorporating insulin dynamics and vitamin C sufficiency. Recognition of the ICV Axis represents a conceptual advancement that can improve therapeutic outcomes across metabolic, endocrine, and integrative medical practice.

Abstract:

Obesity is increasingly recognized as a chronic molecular disease of visceral adipose tissue rather than a simple excess of body weight. Structural remodeling and biochemical damage within adipose depots — particularly extracellular matrix (ECM) degradation and oxidative protein modification — are believed to play a central role in the development of metabolic complications. This study evaluated matrix metalloproteinase (MMP) activity and protein glycooxidation in visceral and subcutaneous adipose tissue, as well as plasma in individuals with obesity. Using a fluorescence resonance energy transfer (FRET)–based assay and fluorimetric quantification of advanced glycation end-products (AGEs), we demonstrated markedly increased activity of all analyzed MMPs (MMP-1, -2, -7, -9, -11, -13) and significantly higher accumulation of selected AGE-related structures (dityrosine (DT), amyloid cross-β-structure, vesperlysine (VES) , pentosidine (PEN)) in visceral adipose tissue of obese patients. These findings indicate that visceral adipose tissue forms a localized inflammatory–proteolytic microenvironment rather than a reflection of systemic circulating pathology. The coexistence of ECM degradation and glycooxidation may mechanistically promote insulin resistance and cardiometabolic risk. These findings suggest that clinical assessment of obesity may require more than anthropometric parameters and circulating biomarkers. Molecular profiling of visceral adipose tissue — directly or via future non-invasive surrogate markers — could improve patient stratification, support personalized metabolic risk prediction and optimize therapeutic decision-making.

Abstract: Selective inhibition of CYP17A1 17,20-lyase activity is a major strategy for hyper-androgenic disorders, aiming to spare 17α-hydroxylase activity and avoid the side ef-fects of non-selective drugs like abiraterone. We investigated tanshinones isolated from Salvia miltiorrhiza (Danshen) using enzyme and cell-based assays. Dihydro-tanshinone (DT) was identified as the most potent and selective compound. At 10 µM, DT inhibited 17,20-lyase by 56.6% while sparing 17α-hydroxylase activity (>93% re-sidual). This corresponds to a lyase/hydroxylase selectivity index of 8.67, far superior to abiraterone (0.73). Furthermore, DT demonstrated lower off-target inhibition of CYP21A2 (14.9%) compared to abiraterone (29.8%). Molecular modeling suggested DT's efficacy stems from a unique, functionally disruptive binding pose rather than superior thermodynamic affinity. DT is a validated natural product lead, and its dual selectivity over both CYP17A1-hydroxylase and CYP21A2 establishes the tanshinone scaffold as a strong candidate for further medicinal chemistry optimization.

Abstract: Background: For decades, the ketogenic diet has been successfully used for the treatment of obesity, metabolic syndrome, and type 2 diabetes. The mechanisms through which it affects metabolism are not fully understood, but the hormonal changes that occur during ketogenic nutrition are likely to play an important role. Methods: One hundred children aged 8–18 years with obesity were enrolled. After baseline anthropometric, biochemical, and hormonal testing, they followed a 4-month “well-formulated ketogenic diet.” Fifty-eight of them successfully com-pleted the study with follow-up assessments. Among them, 8 girls had polycystic ovary syndrome (PCOS) and 7 children had Hashimoto’s autoimmune thyroiditis. Results: At the end of the 4-month period, there was a significant decrease in basal insulinemia (p< 0.0001) and in mean morning cortisol levels (p=0.04), as well as an increase in adiponectin levels (p=0.04). All girls with PCOS experienced spontaneous menstrual cycles, accompanied by a reduction in testosterone levels. TSH levels showed no change for the whole group (p=0.13), but there was a significant decrease in T3 (p< 0.0001) and a mild increase in T4 (p=0.05). Among patients with Hashimoto’s thyroiditis, TSH levels were significantly higher at the end of the study. Conclusions: A short-term, "well-formulated ketogenic” diet in children with obesity induces hormonal changes that support weight loss and improve insulin sensitivity. The diet shows particularly beneficial effects in girls with PCOS and may be considered as part of a comprehensive therapeutic approach in these patients. Monitoring thyroid function during ketogenic nutrition is advisable in patients with hypothyroidism and thyroid disorders.

Abstract: Background: Gestational diabetes mellitus (GDM) is a frequent pregnancy pathology with poor maternal and fetal outcomes and later life risk of type 2 diabetes. Despite known risk factors, such as obesity, age, and familial history, new data suggest that environmental exposure to agents, such as pesticides, can play a role in the etiogenesis of GDM. Objective: The epidemiologic, experimental, and mechanistic evidence between pesticide exposure and GDM risk is summarized here, and we concentrate on recent research (2000–2025). Methods: We conducted a literature search in PubMed, Embase, and the Cochrane Library from 1 January 2000 to 5 October 2025 using combinations of fertilizers, herbicides, pesticides and diabetes mellitus, gestational diabetes. After deduplication, 12 unique studies met inclusion criteria for qualitative synthesis (GDM endpoint or pregnancy glycemia with pesticide exposure). Results: Occupational and agricultural exposure to pesticides during first pregnancy were determined to be associated with a significantly increased risk of GDM through various epidemiologic studies. New studies have implicated new classes of pesticides, including pyrethroids and neonicotinoids, with higher GDM risk with first-trimester exposure. Experimental studies suggest that pesticides provide potential endocrine-disrupting chemicals that can induce insulin resistance through disruption of hormonal signaling, oxidative stress, inflammation, β-cell toxicity, and epigenetic modifications. However significant limitations exist. Most of the evidence is observational, measurement of exposure is often indirect, and confounding factors are difficult to exclude . Notably, low dietary and residential exposure is not well studied, and dose–response relationships are undefined. Conclusion: New data indicate that pesticide exposure during early pregnancy and occupational exposure may increase the risk of GDM. Prospective cohort studies using biomonitoring, chemical mixture exposure, and geographic variation of pesticide exposure should be the focus of future research. Due to potential public health implications, preventive strategies to ensure the quality of nutrition and to reduce maternal exposure to pesticides during pregnancy are rational.

Abstract: Background: Obesity management is evolving with the integration of dual GIP/GLP-1 receptor agonists (Tirzepatide) into comprehensive Digital Weight-Loss Services (DWLSs). While clinical trials demonstrate high efficacy, real-world data are necessary to evaluate long-term adherence and identify predictive markers for patient persistence in these scalable care models. This study retrospectively assessed the 12-month effectiveness and adherence of a Tirzepatide-supported DWLS and identified demographic, clinical, and behavioral predictors of weight loss and program attrition. Methods: Data from 19,693 patients enrolled in the Juniper UK DWLS were analyzed. Adherence was defined by a minimum of 10 medication orders and 12-month weight submission. Weight loss in the full cohort was evaluated using the Last Observation Carried Forward (LOCF) method. Binary logistic and multiple linear regression models identified predictors of adherence and weight loss, respectively. Results: The 12-month adherence rate was 27%. The adherent sub-cohort (n=5,322) achieved a mean weight loss of 22.60 (±7.46) percent, compared to 13.62 (±10.85) percent in the full cohort (LOCF). Long-term adherence and weight loss were positively associated with weekly weight tracking consistency and health coach communication. Conversely, intensive tracking frequency and high weight loss velocity in the first month were sig-nificant inverse predictors of 12-month adherence. Reporting side effects was positively correlated with adherence, suggesting a reporting bias among engaged patients. Conclusion: The DWLS model facilitates maximum therapeutic efficacy for adherent patients. However, patient persistence remains the primary translational challenge. Clinical strategies should prioritize promoting sustainable, moderate behavioral pacing to mitigate attrition risk and optimize the public health effectiveness of medicated DWLSs.

Abstract: Abstract Background: Endocrine complications are increasingly recognized in post-acute COVID-19, but long-term evidence beyond the early pandemic phase remains limited. This study aimed to evaluate incident type 2 diabetes (T2D) and thyroid autoimmuni-ty four years after acute COVID-19 in previously non-diabetic, thyroid-healthy adults. Methods: We conducted a cross-sectional reassessment of adults hospitalized for COVID-19 between August 2020 and July 2021, of whom 96 completed standardized follow-up from January 2024 to June 2025. Baseline data included acute disease sever-ity, admission glucose, inflammatory markers, imaging, and treatments. Reassessment included fasting glucose, thyroid function, anti-TPO/anti-thyroglobulin antibodies, and thyroid ultrasound. Results: At four years, 26 participants (27.1%) developed in-cident T2D, 40 (41.6%) showed thyroid autoimmunity, and 15 (15.6%) had both condi-tions; overall, 47.9% displayed at least one endocrine sequela. Admission hyperglyce-mia strongly predicted later T2D, and T2D prevalence increased with acute disease severity. Additional risk factors included age ≥60 years, hypertension, and se-vere/critical initial illness. Thyroid autoimmunity was frequent but showed no associ-ations with demographic or acute-phase characteristics. Conclusions: Nearly half of previously healthy adults hospitalized for COVID-19 de-veloped long-term endocrine sequelae. Admission hyperglycemia and acute severity identify individuals at higher risk for future dysglycemia, whereas thyroid autoim-munity appears widespread but severity-independent. Long-term metabolic monitor-ing and thyroid screening are warranted in COVID-19 survivors.

Abstract: Myocardial infarction (MI) and heart failure (HF) are associated with low bone mineral density (BMD). We aimed to investigate whether MI and HF directly cause bone loss using 3 different experimental models of cardiac injury. Firstly, terminal myocardial in-farction was induced in adult wild-type mice by coronary ligation, followed by periph-eral quantitative computed tomography (pQCT), histomorphometric, and biochemical analyses at 4 and 9 weeks post-infarction. Secondly, myocardial ischemia-reperfusion injury (I/R) was performed in 4- and 9-month-old rats, followed by bone phenotyping 4 weeks after injury. Finally, transverse aortic constriction (TAC) was performed in adult wild-type mice, double Fgf23/VDR (fibroblast growth factor-23/vitamin D receptor) mu-tants and VDR-deficient mice to investigate bone changes in a HF model caused by af-terload-induced cardiac hypertrophy, 4 and 6 weeks after TAC. We found unchanged BMD after MI, in both the terminal ischemia model in mice and in the myocardial I/R injury model in young and aged rats. On the other hand, TAC significantly reduced es-pecially cortical BMD in femora. Global knockout of Fgf23 in Fgf23/VDR compound mutants did not rescue the TAC-induced skeletal phenotype. Collectively, our data demonstrate that TAC–induced HF, but not MI, is causing bone loss in mice in an FGF23-independent manner.

Abstract: Diabetes mellitus (DM) is associated with a residual cardiovascular risk that persists even when lipid targets are achieved. Within this context, lipoprotein(a) [Lp(a)], an LDL-like particle of genetic origin with pro-atherogenic and antifibrinolytic properties, emerges as a key determinant in the progression of both microvascular and macrovascular complications. Its structural homology with plasminogen promotes thrombosis, while oxidative and glycation modifications amplify endothelial inflammation. Elevated concentrations of Lp(a) (>30 mg/dL; 75 nmol/L), and particularly >50 mg/dL (125 nmol/L), are independently associated with coronary artery disease, ischemic stroke, diabetic nephropathy, retinopathy, and neuropathy. Conventional lipid-lowering therapies exert neutral or modest effects on Lp(a), in contrast with RNA-based targeted agents (antisense oligonucleotides and siRNA[Small Interfering RNA]), which achieve reductions of 70–95% and show consistent results in phase 2 clinical trials. This review integrates molecular mechanisms and clinical evidence, emphasizing the need to incorporate Lp(a) quantification (at least once in a lifetime, and selectively in DM) to refine risk stratification and guide intensive interventions. In diabetic populations, the adaptation of Lp(a)-targeted therapies could redefine the management of residual risk and improve both cardiovascular and microvascular outcomes.

Abstract: Background/Aim: Extracellular-to-total body water ratio (ECW/TBW) and phase angle (PhA, PA) reflect hydration and cellular health, but their relationship with bone, muscle, and fat, as primary components of body composition, is not fully elucidated. This study aimed to evaluate sex-specific differences in body composition and assess the diagnostic potential of ECW/TBW and PhA for low bone/muscle mass and increased fat mass in generally healthy adults. Methods: This post hoc analysis utilized data from a multicenter, cross-sectional, Italian study (2010–2014) that included 18–90 year adults (n=9717). Body composition was measured by bioelectrical impedance (BIA-ACC, Bio-Tekna®), assessing bone, muscle mass, fat mass, ECW, TBW, and PhA. Low bone/muscle mass and adiposity were defined using standard cutoffs. Associations were examined using nonparametric tests and multiple regression analyses. Results: The mean age of men and women was similar (mean ~48 years). Men had significantly higher body mass index (BMI), intramuscular adipose tissue (IMAT%), T-score (bone), S-score (muscle), and PhA, while women had significantly higher fat mass (FM%) and ECW/TBW. ECW/TBW showed excellent discrimination for low muscle mass (AUC 0.845–0.922) and low bone mass (AUC 0.696–0.885), outperforming PhA. Neither ECW/TBW nor PhA reliably predicted increased fat mass. Regression models indicated ECW/TBW was strongly associated with age, sex, BMI, fat mass, and bone/muscle scores (R² = 0.943), whereas PhA’s association was moderate (R² = 0.368). Conclusions: ECW/TBW and PhA reflected sex-specific differences for body composition and effectively identified low muscle and bone mass (with better predictability of the former). Both showed a limited predictive ability for fat mass. Overall, both parameters provide complementary insights into sarcopenia and osteopenia.

Abstract: Healthcare data is experiencing one of the highest growth rates of any major data sector, driven primarily by rapid advances in genomics, medical imaging, and continuous data from wearable devices. The convergence of universal data standards in healthcare (terminologies, OpenEHR, FHIR, and OMOP) is now providing the common ground needed to translate this data into tangible medical advances through a wide array of different applications. Together with a growing ecosystem of analytics, predictive models, and advanced artificial intelligence tools, this synergy is poised to fundamentally transform the delivery of healthcare. With the maturation of health information technology and proliferation of research in the field, the pivotal challenge has shifted from technological capability to the pervasive inability to implement solutions effectively in routine practice, particularly those tailored to diabetic foot-specific needs. In the context of diabetic foot care, where the paramount goals are patients' well-being, tissue preservation, and amputation prevention, collaborative data management must be recognized as a critical treatment modality itself. “Data is tissue,” it is the foundational element that enables the timely, coordinated, and evidence-based interventions necessary for success. This paper highlights some of the opportunities presented by modern data methodologies to address the current implementation gap.

Abstract: Technology has brought about a revolution in the management of type 1 diabetes (T1D). The adoption of continuous glucose monitoring (CGM) and insulin pump therapy in the everyday life of children and adolescents with T1D is a real innovation and the most promising choice for optimizing glycemic control in this population. The incorporation of an alarm system, including notifications, alerts and alarms, warning patients and their parents about glucose levels and upcoming events interfering with safety is an invaluable additional tool for better targeting euglycemia. However, in parallel with clinical benefits of alarm system in ameliorating metabolic control parameters, alarm fatigue was recorded as a phenomenon, negatively affecting everyday life of patients and their caregivers, and as a cause for rejecting or abandoning CGM or pump therapy treatment. There are a few data concerning frequency, consequences and methods of elimination of alarm fatigue among children. As a result, we have conducted a narrative review in order to briefly present the basic philosophy of the existing CGM alarm systems and their positive effect on glycemic management and focus on alarm fatigue; definition, frequency, effect on quality of life and sleep, not only of T1D patients but also of their families, and methods of elimination. Efforts to achieve a more reliable and accurate alarm system and educate on adapting personalized limits and positively interpreting them may protect T1D pediatric population from alarm fatigue and prevent rejection or incomplete use of CGM and insulin pump as the therapeutic choice ensuring the best glycemic control.

Abstract: Introduction: Immune dysfunction plays a significant role in metabolic syndrome, contributing to both IR and chronic low-grade inflammation. This immune dysfunc-tion is characterized by overproduction of inflammatory cytokines among which of primary importance are tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and MCP-1, whereas others such as IFN-γ, IL-17А, and the anti-inflammatory IL-10 appear to be of secondary importance. Cytokines also play a significant role in post-COVID disorders contributing to prolonged immune dysregulation and persistent subclinical inflammation. However, their role in the newly emerging metabolic disorders follow-ing infection remains poorly defined. Methods and materials: In the current study 78 patients (26 men and 52 women) were included, divided into two groups - group 1 (individuals with newly diagnosed car-bohydrate disorders after proven COVID-19 or post-COVID group; n=35) and group 2 (COVID-19 negative persons with Metabolic Syndrome; n=33). They were further di-vided into several subgroups according to type of metabolic disorder present. Standard biochemical, hormonal and immunological parameters were measured using ELISA and ECLIA methods, as wells as some indices for assessment of insulin resistance were calculated using the corresponding formula. Results: Patients from both groups demonstrate similar (P>0.05) metabolic parameters including BMI, lipid profile, uric acid, whereas those from the Post-COVID group demonstrated poor glycaemic parameters (Fasting plasma glucose and HbA1c) (P< 0.05). Patients from both Post-COVID and COVID-negative group demonstrated high levels of IR, the latter having higher mean values of both indices. Higher TNF-α and IL-10 values were registered in the Post-COVID group (P>0.05) whereas higher levels of INF-γ (P< 0.001) and IL-17A we registered in the COVID-negative group (P>0.05). A lot of correlations were found between the immunological parameters evaluated and the metabolic ones. Conclusion: The observed changes in both metabolic and immune parameters studied among the two groups show many similarities, but some significant differences have also been identified. What can be asserted is that cytokines definitely have an im-portant role in Post-COVID newly-emerging metabolic disorders contributing to both adipose tissue dysfunction, IR, dysglycaemia and dyslipidemia observed.

Abstract: Diagnosis of type 2 diabetes using the classical clinical and laboratory biomarkers (HbA1c, glucose, lipids, BMI, and blood pressure) is a classification by symptoms and does not provide insight into the underlying pathophysiological disorders (insulin resistance, ß-cell dysfunction, visceral adipose tissue hormonal secretion, and chronic systemic inflammation). A better understanding of these disorders may help for the selection of appropriate and potentially more successful personalized therapeutic interventions. Based on an extensive clinical trial experience, a method for individual phenotyping and consecutive personalized diabetes therapy has been developed in our practice, which we have been using for more than 15 years and which we would like to share for discussion and debate. In this part 1, the pathophysiological background and the diagnostic approach to phenotyping will be described. A consecutive part 2 will present the translation of the phenotyping result into a personalized diabetes therapy and will provide real-world patient examples when practicing this concept.

Abstract: Background/Objectives: Patients with differentiated thyroid cancer (DTC) receive thyroxine substitution targeting thyroid-stimulating hormone (TSH) levels adapted to their response-to-treatment category. However, variations in prescription and TSH inter-assay variability may result in over- or undertreatment. Methods: We measured TSH in 220 consecutive DTC patients using three automated immunoassay platforms (Elecsys, Atellica, Alinity). Each patient was assigned to a response-to-therapy category (Excellent Response [ER], Indeterminate Response [IndR], Biochemical Incomplete Response [BIR], Structural Incomplete Response [SIR]) by an experienced thyroid oncologist. We defined recommended TSH targets according to the American Thyroid Association (ATA) 2015 guidelines and the response-adapted ATA 2025 framework that allows progressive relaxation of TSH suppression in patients with ER while maintaining tight suppression in those with persistent disease. Analytical agreement between assays was assessed using Passing-Bablok regression and Bland-Altman analysis. Clinical appropriateness was evaluated by classifying each measured TSH value as below, within, or above the recommended range for that patient's response category. Results: The three immunoassays demonstrated high analytical agreement with only minor biases unlikely to affect clinical interpretation. However, large deviations from guideline-defined TSH targets were observed. Among ER patients, 37% remained oversuppressed despite the absence of active disease. Conversely, in IndR or BIR patients, 76% had TSH levels above the recommended range, indicating undersuppression where residual disease cannot be excluded. SIR patients were generally managed appropriately. The ATA 2025 framework reclassified more ER patients as appropriately managed, but undersuppression persisted in non-ER patients. Conclusions: Guidelines are not uniformly applied in thyroxine dosing for DTC patients. TSH immunoassays have achieved adequate analytical performance. The focus must now shift toward addressing clinical, educational, and systemic factors that pre-vent optimal levothyroxine management.

Abstract: Congenital hypothyroidism (CH) is one of the most common endocrine disorders of childhood. The primary form of CH is attributable to thyroid dysgenesis (agenesis, hypoplasia, or ectopy) in 65-85% of cases, with the remaining cases being attributed to dyshormogenesis. Thyroid dysgenesis was considered a sporadic disease. However, the recent advantages of molecular techniques have significantly contributed to the understanding of the pathogenesis of the disease. The higher prevalence of congenital malformations and syndromes in patients with CH compared to the general population supports the genetic basis. This narrative review aims to provide an overview of the identified and potential genetic causes of thyroid dysgenesis. Mutations in ten genes involved in thyroid gland development during embryogenesis, TSHR, PAX8, NKX2-1, NKX2-5, FOXE1, JAG1, NTN1, GLIS3, CDC8A, and TUBB1, have been identified in cohorts of patients with thyroid dysgenesis. However, most cases remain unexplained. Novel candidate genes have been proposed. The extant evidence suggests that the pathogenesis of thyroid dysgenesis involves a spectrum of genetic etiologies, ranging from monogenic to multigenic, and that epigenetic or environmental factors may also contribute. As molecular techniques are continuously refined, future studies are expected to elucidate the complex genetic background of thyroid dysgenesis.

Abstract: Vitamin D (VD), due to its hormonal action, plays a crucial role in calcium homeostasis and bone metabolism, and its deficiency has been associated with musculoskeletal disorders such as osteoporosis, fractures, and osteomalacia, as well as a growing range of chronic conditions and certain cancers. Despite its physiological relevance and widespread prevalence, particularly among older individuals, patients with chronic diseases, institutionalized populations and pregnant or lactating women, clinical approaches to diagnosing and managing vitamin D deficiency (VDD) remain heterogeneous across guidelines and healthcare settings. This reflects a lack of consensus regarding the benefits and limitations of universal versus selective screening, the definition of adequate serum concentrations, and the clinical indications for supplementation across different patient profiles. This narrative review explores key controversies in the clinical management of VDD, including current perspectives on screening strategies and target populations, indications for empirical supplementation, criteria for biochemical monitoring, and therapeutic goals in bone-related outcomes. In particular, the review discusses the rationale for adopting a 30 ng/mL (75 nmol/L) threshold for adequate serum 25-hydroxyvitamin D levels in skeletal health, the role of vitamin D and calcium in osteoporosis treatment, and the pharmacological advantages of cholecalciferol compared to other vitamin D compounds. Through a synthesis of available evidence and expert consensus, the review aims to support clinical decision-making in the prevention and treatment of VDD and to identify areas that require further clarification or research. This review aims to support evidence-based clinical decision-making.

Abstract: Diabetes mellitus (DM) is a chronic metabolic disorder characterized by an impaired insulin secretion (or action), leading to persistent hyperglycemia. Such a disease, associated with multiple risk factors, can be broadly classified into two major types: Type 1 and type 2 diabetes. In recent years, herbal medicines (HMs) have been gaining significant attention as alternatives or complementary therapeutic options, owing to their rich content of bioactive compounds. These natural agents have been widely investigated for their potential in the prevention and management of several chronic diseases, including (i) cardiovascular disorders, (ii) infections, and notably (iii) diabetes mellitus. In this present state-of-the art review, we highlight the roles and impacts of various medicinal plants originating from diverse families upon emphasizing their active phytoconstituents, and the mechanisms through which they exert antidiabetic effects. Special emphasis is placed on how these bioactive ingredients can modulate glucose metabolism, enhance insulin sensitivity, and ultimately mitigate complications related to diabetes.

Abstract: Clostridial myonecrosis infection with a swift onset of progression results in a high mortality rate. The main pathogen of the issue is Clostridium perfringens. The diabetic patients are prone to showing higher susceptibility to developing foot ulcers due to several reasons, such as vascular insufficiency, neuropathy, and impaired wound healing. Furthermore, diabetics suffer from systemic complications like sepsis and multi-organ failure. Advanced necrosis of tissue leads to limb amputation, with the lower limb being amputated more than the upper extremities. The treatment process challenges include: hyperglycemia, which complicates management; risks of reinfection; and slower healing. Early detection is crucial, as surgical removal of damaged tissue combined with broad-spectrum antibiotics remains an important part of treatment. Patients who experienced hyperbaric oxygen therapy (HBOT) and negative pressure wound therapy (NPWT) are more likely to experience better survival outcomes, as these procedures result in vascular repair, tissue oxygenation, decreased risk of reentrance of bacteria, and lower rates of amputation. This is a retrospective review of both historical and recent literature in clinical, microbiological, and treatment aspects of gas gangrene developed in the context of diabetes.

Abstract: The present review examines the most recent data regarding molecular mechanisms linking OSA and T2DM, analyzing key biomarkers including hypoxia-inducible factors (HIF 1α), inflammatory mediators, adipokines, microRNAs, hormones, and neuropeptides that serve as both diagnostic indicators and potential therapeutic targets. Key molecular findings from the scientific literature report elevated HIF-1α promoting insulin resistance, decreased SIRT1 levels, dysregulated microRNA-181a and microRNA-199a, increased inflammatory cytokines (TNF-α, IL-6, CRP), and altered adipokine profiles with reduced adiponectin and elevated leptin and resistin. Current clinical evidence reveals significant therapeutic potential for modern anti-diabetic medications in the management of OSA. GLP-1 receptor agonists, particularly tirzepatide, that received FDA approval as the first medication for moderate-to-severe OSA in obese adults, showing 55-63% AHI reduction. SGLT2 inhibitors also demonstrate promising results through weight loss and cardiovascular protection mechanisms. This integrated approach represents the evolution toward comprehensive OSA management beyond traditional mechanical ventilation strategies. Future research should focus on developing personalized treatment algorithms based on individual molecular biomarker profiles, investigating combination therapies, and exploring novel targets, including chronotherapy agents.