Search Results (487)

Polycystic ovarian syndrome (PCOS) is a complex endocrine and metabolic disorder that affects reproductive health, metabolic function, and long-term cardiovascular health in women of reproductive age. The syndrome is characterized by hyperandrogenism, chronic anovulation, insulin resistance, oxidative stress, and ovarian microenvironment remodeling. While current treatments focus on symptom relief through hormone regulation, insulin sensitizers, or ovulation induction, there is a need to target the underlying molecular and cellular processes that drive disease progression and infertility. Breakthroughs in reproductive and metabolic medicine have led to the development of next-generation therapeutics for PCOS that aim to restore ovarian function at the molecular level. Nanoparticle- and nanofiber-based drug delivery systems offer targeted delivery to the ovaries, improved bioavailability, and controlled release of insulin sensitizers, antioxidants, and anti-androgens. Metabolic reprogramming strategies that target insulin resistance, mitochondrial dysfunction, and autophagy have emerged as potential disease-modifying interventions. In addition, AI-enabled precision medicine approaches are reshaping PCOS management through phenotype-based classification, predictive modeling, and personalized fertility optimization. In this review, we highlight recent advancements in understanding the molecular pathophysiology of PCOS and introduce novel therapeutics that harness intelligent drug delivery, ovarian microenvironment restoration, and AI-based interventions. We discuss the potential of these innovative strategies to update PCOS management options for long-term ovarian restoration and fertility. Full article

Background: Noninvasive transdermal insulin delivery using ultrasound technology has gained attention for improving the glycemic control of insulin-dependent patients. Methods: Indirect functional comparison and evaluation of insulin dosage, between noninvasive ultrasound-mediated transdermal delivery and needle injection methods, was achieved utilizing in vivo blood glucose measurements of temporary hyperglycemic rabbits. Nine rabbits were divided into three groups: (i) untreated control, (ii) subcutaneous injection and (iii) ultrasound-mediated transdermal delivery. Animals were anesthetized using a combination of ketamine hydrochloride and sodium xylazine to produce temporary hyperglycemic rabbits during the experiments. The rabbits in the control group did not receive insulin, while the animals in the ultrasound group received insulin transdermally for 10 min utilizing a customized single-element piston-shaped ultrasound transducer operated by multi-frequency electrical signals from 100 to 200 kHz. Rabbits in the direct subcutaneous injection group were anesthetized and injected with 0.25 units/kg of insulin. Results: With an initial blood glucose baseline level of 228.7 ± 13.1 (mg/dL) for all rabbits, the in vivo results of control group showed an increase above the baseline by 129.7 ± 27.3 (mg/dL) at the end of the in vivo experimental period (80 min). However, the ultrasound-mediated delivery and subcutaneous injection groups showed noticeable statistically significant percentage reductions in blood glucose levels by 43.9 ± 5.4 and 42.7 ± 6.6, respectively, compared to the control group by the end of the in vivo experiments. Conclusions: In vivo glucose response results confirmed that piston-shaped ultrasound transducers achieved indirectly similar insulin dosage delivery by ultrasound energy for tested animals with no statistically significant differences once compared to the results of the subcutaneous needle injection group. Full article

Background/Objectives: Impairment in pulsatile insulin release contributes to insulin resistance and is one of the earliest markers of developing type 2 diabetes. Insulin delivered to the liver in pulses has a stronger glucose-lowering effect than continuous insulin delivery. Whether pulsatility benefits the islet itself is an open question. We previously showed that reducing glucokinase activity with the glucokinase inhibitor D-mannoheptulose (MH) improves function in islets exposed to prolonged hyperglycemic conditions. In this study, we test whether pulsatile vs. continuous delivery impacts the effectiveness of MH in islets. Methods: Islets were exposed to high-glucose conditions (20 mM glucose) for 24 or 48 h to induce early adaptations to hyperglycemia. We then used a specially designed perifusion system to impose pulsatile activity by exposing mouse islets to 3 min of MH in 20 mM glucose and 3 min of only high levels of glucose. Islets given intermittent MH for 18 h were compared with continuous delivery of MH at a full (2.5 mM) or half (1.25 mM) dose. Results: MH delivered by the forced oscillatory system reversed the effects of hyperglycemia and restored glucose sensing more effectively than continuous delivery. Specifically, fura-2AM imaging of intracellular calcium showed that islets given pulsatile MH had greater reductions in the elevated basal calcium caused by hyperglycemic conditions, improved the glucose stimulation index, and improved phase 0 response (indicating glucose-stimulated calcium uptake by the endoplasmic reticulum). Conclusions: These findings suggest that the loss of oscillatory glucose metabolism in islets contributes directly to beta-cell dysfunction. Full article

The global population is ageing due to increased life expectancy, and the prevalence of diabetes is proportionally increasing. With advancing age, diabetes in older people is a complex condition due to associated morbidities and geriatric syndromes. As a result, the management of diabetes in old age is challenging. Due to the wide heterogeneity of older people, diabetes management in this age group should be personalised. While strict targets are accepted in fit individuals, relaxed targets should be considered in patients with multiple morbidities and a high risk of hypoglycaemia. The development of frailty changes the metabolic profile of older people, and their insulin resistance and diabetes trajectory, which will have an impact on the choice of glucose-lowering agents and the goals of therapy. For example, intensive therapy, the use of SGLT-2 inhibitors and GLP-1RA, and tight targets should be continued in frail, sarcopenic, obese individuals due to their increased insulin resistance and cardiovascular risk. On the other hand, relaxed targets and deintensification of therapy should be considered in anorexic, malnourished, frail individuals with significant weight loss due to their low insulin resistance, low prevalence of cardiovascular risk factors, and high risk of hypoglycaemia. Annual reviews of older people with diabetes should include screening for frailty, depression and dementia for early diagnosis, and appropriate interventions. The introduction of continuous glucose monitoring is increasingly used in older people with diabetes and has the potential to reduce the incidence of hypoglycaemia. With the expectation of a continued increase in the prevalence of older people with diabetes, the use of mobile health may allow care delivery on a wider scale without the need for face-to-face appointments. In addition, there is a promising scope for artificial intelligence to achieve better diabetes outcomes. Future research is still required to expand the use of these technologies in older age groups. Full article

Background/Objectives: Continuous glucose monitoring (CGM) has transformed diabetes management by enabling high-resolution assessment of glucose dynamics, with well-established use in type 1 diabetes (T1D) and insulin-treated type 2 diabetes (T2D), and expanding applications across broader populations, including non-insulin-treated T2D and gestational diabetes. However, real-world implementation remains constrained by economic barriers, fragmented reimbursement, workflow challenges, and limited capacity for continuous data interpretation. This review examines key barriers to CGM implementation and synthesizes current evidence on pharmacist-integrated CGM care as an emerging model to support CGM adoption across clinical and community-based settings. Methods: A narrative literature review was conducted to synthesize evidence on pharmacist-integrated CGM services in diabetes care. Literature was identified through structured searches of PubMed, Embase, and the Cochrane Library, supplemented by Google Scholar and citation tracking, covering publications from January 2010 to December 2025. Studies were selected based on predefined criteria, including those reporting clinical outcomes, pharmacist involvement, or health system and implementation factors related to CGM use. Relevant survey-based and real-world studies were also considered to capture healthcare professionals’ perspectives and implementation experiences. Evidence was synthesized thematically across clinical, behavioral, and health system domains. Results: Available evidence suggests that pharmacist-integrated CGM care is associated with improvements in glycemic management, including increased time in range, reduced glycemic variability, and more timely pharmacotherapy optimization. Pharmacist involvement may also support patient education, self-management, and engagement with digital health technologies, and facilitate ongoing data interpretation and treatment adjustment between clinical encounters. However, evidence remains heterogeneous and geographically limited, with predominantly retrospective and pilot studies and few randomized trials, constraining the robustness and external validity of the findings. Further studies are needed to confirm its clinical effectiveness, comparative effectiveness, and economic value. Conclusions: Pharmacist-integrated CGM represents a promising and operationally feasible approach to supporting CGM use in routine diabetes care. While current evidence indicates potential benefits in glycemic management and care delivery processes, further research and implementation efforts are required to support its effective and sustainable adoption across diverse healthcare settings. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is a prevalent metabolic disease associated with maternal and neonatal complications. Diets enriched with extra virgin olive oil may benefit metabolism and provide antioxidant effects. We aimed to evaluate the effects of dietary supplementation with extra virgin olive oil on metabolic parameters and insulinization rate in women with GDM. Methods: This is a multicenter, parallel, randomized controlled trial in which 190 patients with GDM were enrolled before week 29 of gestation and randomized into the Control group and the Intervention group. Patients in the Intervention group received the indication to consume three tablespoons of extra virgin olive oil (EVOO) daily. At term, metabolic parameters, insulin requirement and maternal and neonatal outcomes were evaluated. Results: Control and Intervention groups showed no differences in maternal age (31.7 ± 6.0 and 32.4 ± 5.2 years, respectively) or gestational age (26.5 ± 3.6 and 26.7 ± 3.3 weeks, respectively) at enrollment. Primary outcomes showed that EVOO consumption was associated with a reduction in insulin requirement (RR 0.595, 95% CI 0.361–0.967, p < 0.05). There was a significant reduction in triglyceridemia in the EVOO-supplemented group compared to controls (MD −43.3 mg/dL, 95% CI −66.8–−19.8, p < 0.01). There were no effects of the intervention on gestational weight gain. As secondary outcomes, maternal BMI and gestational age at delivery showed no changes between the groups. Although maternal and neonatal composite outcomes were not significantly reduced, the rate of neonates with more than one complication (RR 0.340, 95% CI 0.133–0.870, p < 0.05) and NICU requirement (RR 0.367, 95% CI 0.140–0.939, p < 0.05) were significantly reduced in the Intervention group. Conclusions: In GDM, maternal dietary supplementation with extra virgin olive oil resulted in reduction in maternal triglyceridemia, need of insulinization and neonatal complications. Full article

Proportional–integral–derivative (PID) controllers are always a preferred choice of control strategy in industrial and biomedical systems due to their simplicity, reliability, and easy implementation. However, the systematic tuning of PID parameters for nonlinear, constrained, and safety-critical systems remains challenging, particularly in the presence of disturbances and actuator limitations. This paper presents a unified surrogate-based optimization framework for tuning PID controllers for linear and nonlinear dynamical systems. The tuning problem is formulated as a constrained optimization task, where performance objectives and safety requirements are explicitly incorporated into the cost function. A surrogate-based optimization via clustering (SBOC) approachis employed to efficiently explore the PID parameter space while reducing the number of expensive closedloop simulations. The proposed framework is first applied to the first- and second-order linear time-invariant systems to check its feasibility and then to the nonlinear systems to demonstrate its robustness under nonlinearity and saturation. The approach is further applied to safety-critical systems considering the case of glucose regulation in type 1 diabetes under realistic meal disturbances and insulin delivery constraints. The simulation results show that the surrogate-optimized PID controller achieves stable regulation with improved tracking performance while strictly satisfying safety requirements, including control effort penalties to limit actuator wear and the avoidance of hypoglycemia and hyperglycemia in glucose regulation problems. Full article

Endothelial cells have emerged as critical peripheral nutrient sensors that actively regulate systemic lipid metabolism rather than serving as passive conduits. Endothelial peroxisome proliferator-activated receptor γ maintains redox balance, supports nitric oxide-dependent perfusion, and preserves insulin sensitivity during high-fat feeding, while ghrelin signaling through endothelial GHS-R promotes triglyceride clearance and lipid uptake into white adipose tissue through an endothelial peroxisome proliferator-activated receptor γ-dependent program. These pathways reveal that the endothelium integrates hormonal and metabolic cues to tune lipid trafficking, vectorial fatty acid delivery, and depot-specific energy storage. The concept that the endothelial phenotype, rather than circulating lipid levels alone, determines organ-level lipid exposure reframes endothelial lipid sensing as a key regulator of whole-body metabolic homeostasis. Understanding how endocrine and transcriptional pathways shape endothelial lipid handling may reveal new therapeutic targets for the treatment of obesity, dyslipidemia, and related metabolic diseases. Full article

The ADA 2026 Standards of Care in Diabetes introduces pivotal updates that refine diagnostic and therapeutic workflows. Expanding upon the 2025 guidelines, the 2026 edition broadens continuous-glucose-monitoring (CGM) eligibility to include all individuals on insulin or non-insulin therapies where CGM aids management. Significant new guidance addresses hyperglycemia management in oncology, identifying metformin as the preferred first-line intervention for drug-induced glycemic excursions. Additionally, type 1-diabetes (T1D) risk stratification is refined; a confirmed single IA-2 autoantibody now warrants monitoring levels similar to the Stage 2 disease. Furthermore, prerequisites for automated-insulin-delivery (AID) initiation have been removed to streamline technology access. For laboratory professionals, these revisions emphasize the critical role of advanced glycemic metrics and precise autoantibody profiling in complex clinical contexts. Full article

Gestational Diabetes Mellitus (GDM) is the most common metabolic complication of pregnancy, affecting approximately 14% of pregnancies globally. Despite the frequent normalization of glycemic parameters immediately after delivery, GDM is an important precursor of subsequent chronic disease, increasing the risk of type 2 diabetes (T2DM). Current international guidelines suggest just a strictly observational approach during the immediate puerperium, recommending metabolic screening only between 6 and 12 weeks postpartum. This has contributed to the creation of a therapeutic “orphan window” where women receive no specific metabolic support, leaving their metabolic status unassessed and unmanaged. We postulate that the immediate postpartum period represents a critical window of “metabolic plasticity” where the abrupt cessation of placental hormones offers a unique opportunity to restore insulin sensitivity and promote “beta-cell rest” before the onset of irreversible dysfunction. Consequently, this narrative review and perspective examines the epidemiological urgency of the GDM-to-T2DM transition and provides a biological rationale for early pharmacological or nutraceutical intervention. Specifically, we discuss the limitations of metformin and present the hypothesis of myo-inositol combined with alpha-lactalbumin as a safe, lactation-compatible “bridging therapy” to preserve beta-cell function, improve compliance, and modify the natural history of diabetes in this high-risk population, highlighting that this theoretical proposal requires validation through future clinical trials. Full article

Adipose tissue serves as a critical metabolic and endocrine organ, essential for maintaining systemic energy homeostasis and inter-organ communication. During the aging process, it undergoes significant structural remodeling and functional decline, characterized by dysregulated lipid metabolism, chronic low-grade inflammation, reduced insulin sensitivity, and adipokine imbalance. These alterations not only compromise the physiological integrity of adipose tissue but also contribute to the progression of various age-associated metabolic disorders, including type 2 diabetes, atherosclerosis, and nonalcoholic fatty liver disease. In recent years, natural products have emerged as a focal point in anti-aging research, owing to their broad accessibility, high biological safety, and capacity for multi-target regulation. Polyphenolic and polysaccharide, in particular, have demonstrated robust antioxidant, anti-inflammatory, autophagy-modulating, and mitochondrial-protective effects in cellular and animal models, indicating their promise in attenuating adipose tissue aging. Although the anti-aging effects of these natural compounds are well documented in the neural, hepatic, and cardiovascular systems, their specific mechanisms in adipose depots—especially differential regulatory patterns between white and brown adipose tissues, which may inform depot-specific therapies—and the development of targeted delivery approaches remain inadequately explored. This review, grounded in the three primary hallmarks of adipose tissue aging (oxidative stress, chronic inflammation, and dysregulated lipid metabolism), systematically elucidates the molecular mechanisms and recent advancements in the application of polyphenols and polysaccharides as natural modulators. This review establishes a cohesive theoretical foundation and delivers innovative perspectives to guide the advancement of natural product-based nutritional and therapeutic strategies for combating adipose tissue aging. Full article

Carbon nanoparticles (CNPs) are increasingly being considered for medical applications. The objective of this article is to determine which anti-diabetic drugs and compounds have been enhanced by CNPs, and which CNP scaffolds were found to be successful. The anti-diabetic drugs administered loaded on CNPs include insulin, metformin, glimepiride and vanadium compounds. Carbon quantum dots (CQDs), graphene quantum dots (GQDs), graphene oxide quantum dots (GOQDs), hybrid systems and fullerenes are all carriers able to alleviate symptoms of diabetes. Successful CNPs are 10 nm or less and can have a flat pancake structure, as well as the spherical CQDs and the spherical-but-hollow gadofullerene (Gd-C82). The use of the carbon nanoparticle scaffold includes oral, intravenous administration and placement as an implant in a diabetic animal model system. In vitro studies in an insulin-resistant model demonstrate a 500–1000-fold enhancement of metformin when placed on the pegylated GOQD. Although some CNPs have low toxicity, more information is needed for understanding the metabolism associated with uptake and processing. In summary, CNPs represent a novel class of nanoparticles that has promising potential. They enhance the efficacy of anti-diabetic drugs, have low toxicity, and keep the loaded drug protected until reaching their targets. Full article

Objectives: To describe a structured transition model for individuals with type 1 diabetes mellitus (T1DM) from pediatric to adult care in a tertiary hospital, and to explore demographic, clinical, and psychosocial factors associated with glycemic outcomes. Research Design and Methods: We conducted an observational, cross-sectional study including all patients with T1DM who transitioned from the Pediatric Endocrinology Clinic to the Adult Endocrinology and Nutrition Unit at Virgen del Rocío University Hospital between 2021 and 2024. Demographic, clinical, biochemical, glucometric, and socioeducational variables were collected at the first adult care visit. Statistical analyses included nonparametric tests and exploratory multivariate logistic regression models. Results: A total of 73 patients (45% female) were included, with a median age of 18 years and median diabetes duration of 9 years. The 46.6% of our cohort had an HbA1c > 7.5%. Overweight and obesity were present in 25% and 8% of patients, respectively, and 11% were active smokers. Eighteen percent were receiving mental health follow-up, mainly for anxiety–depressive disorders. Those using hybrid closed-loop insulin delivery and continuous glucose monitoring achieved significantly better glycemic control (TIR 67% vs. 48%; p < 0.01) and lower glycemic variability. In exploratory multivariable analyses, continuous glucose monitoring use > 90% of the time and higher maternal educational level were associated with a lower likelihood of HbA1c > 7.5%. Conclusions: In this cross-sectional transition cohort, intensive use of diabetes technology and higher maternal educational level were associated with better glycemic control at the time of transfer to adult care. These findings should be interpreted as exploratory and hypothesis-generating, and warrant confirmation in larger, prospective studies. Full article

Background: Despite major advances in insulin formulations and delivery systems since 1921, many people with diabetes (PwDs) still fail to achieve recommended glycemic targets. Common reasons include inadequate education, injection errors, and poor adherence due to factors such as needle phobia and pain. Recognition of these barriers has driven the development of improved injection systems, particularly thinner and shorter needles. An experimental study previously identified the Pic Insupen 34 G 3.5 mm needle as high performing. We therefore conducted an observational study to assess its acceptability directly among PwDs. Methods: This multicentre, open-label, real-world study enrolled 300 insulin-treated PwDs who compared their usual pen needle (30–33 G) with the new 34 G × 3.5 mm needle over two two-week periods. The primary outcome was perceived puncture pain. Results: Participants overwhelmingly preferred the 34 G needle, based on the following findings: Pain perception: 62% of 34 G users reported minimal or no pain, compared with only 8% using their previous needle. Conversely, 22% of participants reported the highest pain score with their old needle, compared with just 5% using the 34 G. Ease of use: 77% rated the 34 G needle at the highest level of ease of use, compared with 20% for their previous needle. Complications: The 34 G needle was linked to significantly fewer hypo-/hyperglycemic episodes and local skin complications such as bruising or irritation. Eighty per cent reported no glycemic fluctuations while using the 34 G needle. Robustness: Ninety-four per cent of PwDs never observed the 34 G needle bending during use, compared with 64% using their previous needle, confirming greater robustness despite its thinner profile. Conclusions: The Insupen^® 34 G × 3.5 mm needle substantially reduces puncture pain and improves the overall manageability of insulin injections. Its innovative design—combining reduced thickness with optimised tip geometry—is associated with fewer complications and enhanced injection performance. Because reduced pain and ease of use are critical for improving adherence to insulin therapy, the features of the 34 G needle should inform future prescribing decisions. Full article

This work introduces a new mathematical model designed to describe the glucose–insulin dynamics associated with a glucose-responsive smart microneedle patch reported in the literature. The model captures the complete sequence of the patch behavior, from detecting glucose changes to controlled transdermal insulin delivery and gradually restoring blood glucose levels to the normal range. Our simulations show that the patch can effectively manage glucose not only during fasting conditions but also after single and multiple meals, restoring glucose levels to healthy levels within a short period. The model predictions are consistent with experimentally reported trends in previously published studies, which strengthens confidence in the biological realism of the proposed mechanism. Because some parameters in such systems are difficult to measure directly, we also performed a comprehensive sensitivity analysis to understand how variations in key parameters influence system stability. The results highlight the central role of the insulin release rate and the five glucose–regulation parameters examined in the sensitivity analysis, providing clear guidance on the most critical aspects of patch design for reliable performance. Overall, this study provides a simplified yet robust mathematical framework that makes the behavior of a glucose-responsive microneedle patch easy to understand and analyze. It lays the groundwork for future refinement of control strategies and optimization of patch design, improving control strategies, and developing more advanced systems that can maintain healthy glucose levels naturally and intuitively. Full article