Search Results (30)

An overview of seasonal variations in glycaemic patterns in children and young adults with type 1 diabetes has been addressed in a previous work, which paved the way for an in-depth study involving not only traditional Multiple Dose Injection (MDI) therapy, but also a comparative analysis with the use of Advanced Hybrid Closed-Loop (AHCL) insulin pumps. The widespread use of Flash Glucose Monitoring (FGM) and Continuous Glucose Monitoring (CGM) systems, as well as dedicated platforms for synchronizing and storing CGM reports, has facilitated an efficient approach to analyzing glycaemic patterns. The effect of environmental parameters on glycemic trends undoubtedly has a clinical relevance, which however can be appropriately managed by knowing the responses in patients treated with different therapeutic approaches. In this sense, it is possible to evaluate how the glycemic trend in diabetic patients, in relation to external temperatures, responds differently to therapies. In this work, the response, in terms of glucose level, in diabetic patients was analyzed, according to the different therapeutic approaches and in relation to variations in external temperature. For the same period of the previous work (one year: Autumn 2022–Summer 2023), seasonal variations in CGM metrics (i.e., Time In Range—TIR, Time Above Range—TAR, Time Below Range—TBR and Coefficient of Variation—CV) were analyzed. The results show a better metabolic control, linked to the effect of the algorithm on the trend of glycaemia. However, the analysis focused on the heatwave of July 2023 highlights the role of extreme temperatures as a stress factor in the insulin pumps performance. A further focus was carried out on the comparison of glycaemic patterns during the school and non-school period for all patients until 21 years old. Results suggest that during the school period, glycaemic patterns, in patients treated with MDI, show a greater onset of hyperglycaemia. From all that has emerged, it appears clear that structured education on diabetes self-management for patients and their families is fundamental and must take into account multiple factors (type of therapy, daily activities, atmospheric temperature) in order to keep their effects under control. Full article

Background and Objectives: Automated insulin delivery (AID) systems represent a major advancement in type 1 diabetes (T1D) management, particularly in pediatric populations. However, real-world evidence comparing their effectiveness to conventional multiple daily injection (MDI) therapy in youth remains limited. This study aimed to evaluate the impact of transitioning from MDI therapy to AID systems on glycemic control in children and adolescents with T1D, and to explore potential differences based on baseline HbA1c levels and device type. Materials and Methods: In this single-center, retrospective observational study, 76 children and adolescents with T1D were evaluated before and after switching from MDI to either the Medtronic MiniMed™ 780G or Tandem t:slim X2™ Control-IQ system. Glycemic control was assessed using continuous glucose monitoring (CGM)-derived metrics at three time points: the last 15 days of MDI therapy (T0), 15 days after (T1), and 6 months after (T2) AID initiation. Statistical comparisons were conducted across time points and between subgroups stratified by baseline HbA1c and AID system. Results: Significant improvements in glycemic control were observed as early as 15 days after AID initiation, with sustained benefits at 6 months. Time in range (TIR) increased from 62.0% at baseline to 76.7% at 15 days and 75.8% at 6 months, and time in tight range (TITR) from 39.8% to 53.9% at T1 and 52.1% at T2 (both p < 0.001). Improvements were more pronounced in participants with higher baseline HbA1c (+16.9% for TITR and +22.3% for TIR). No significant differences in glycemic outcomes were observed between device groups, although algorithm-driven differences in insulin delivery patterns were noted. Total daily insulin dose and BMI increased significantly over time (p < 0.001 and p = 0.008, respectively). Conclusions: AID therapy leads to rapid and sustained improvements in glycemic control among youth with T1D, particularly in those with suboptimal baseline control. These benefits highlight the clinical value of AID systems, while also emphasizing the need for monitoring potential metabolic impacts. Full article

Background/Objectives: Type 1 diabetes mellitus (T1D) is the most common metabolic disorder in children, with significant physical and emotional impacts. Achieving optimal glucometric control is challenging due to the complex management and limitations of insulin therapy. Advances in pharmacology and technology, including continuous glucose monitoring (CGM) systems, offer new options for diabetes management. We developed Andiacare, an open-source platform for macro/micro-management of diabetes and analyzed its application in a pediatric T1D cohort to evaluate glucometric control patterns. Methods: A retrospective cohort study was conducted in a pediatric population (<18 years old) in Andalusia, Spain. Patients treated with Multiple Daily Injections of Insulin (MDI) and FreeStyle Libre 2 System (Abbott, Spain) were included. The patient data were analyzed using the Andiacare platform, which categorizes patients based on the Advanced Technologies and Treatments for Diabetes (ATTD) panel’s targets for glucometric control. Results: The study included 2215 patients from 18 pediatric hospitals. The Andiacare platform categorized patients into four groups based on glucometric control parameters, enabling patient stratification based on their glucometric control. Only 25.8% of the cohort achieved the recommended Time in Range (TIR), and 9.5% of the patients achieved all target parameters of glucometric control. Age is a determinant factor in adherence and achievement of set goals. Conclusions: This study offers insights into glucometric control in a large pediatric population with T1D in Andalusia. Few patients achieved the recommended glucometric control targets, highlighting the need for improved management strategies. The use of digital platforms such as Andiacare might contribute to facilitating the management of large pediatric cohorts. New algorithms integrating glucometric and non-glucometric parameters are required for improved individual and cohort categorization to optimize therapeutic interventions. Full article

Breast cancer (BC) is the most common malignancy and the second-leading cause of cancer-related mortalities in women. Epidemiological studies suggested the reduced BC incidence in Mediterranean populations due to the daily consumption of diets rich in extra-virgin olive oil (EVOO). EVOO secoiridoid phenolics are widely known for their positive outcomes on multiple cancers, including BC. The current study investigates the suppressive effects of individual and combined EVOO phenolics for BC progression and motility. Screening of a small library of EVOO phenolics at a single dose of 10 µM against the viability of the BC cell lines ZR-75-1 (luminal A) and MDA-MB-231 (triple negative BC, TNBC) identified oleocanthal (OC) and ligstroside aglycone (LA) as the most active hits. Screening of EVOO phenolics for BC cells migration inhibition identified OC, LA, and the EVOO lignans acetoxypinoresinol and pinoresinol as the most active hits. Combination studies of different olive phenolics showed that OC combined with LA had the best synergistic inhibitory effects against the TNBC MDA-MB-231 cells migration. A combination of 5 µM of each of OC and LA potently suppressed the migration and invasion of the MDA-MB-231 cells versus LA and OC individual therapies and vehicle control (VC). Animal studies using the ZR-75-1 BC cells orthotopic xenografting model in female nude mice showed significant tumor progression suppression by the combined OC-LA, 5 mg/kg each, ip, 3X/week treatments compared to individual LA and OC treatments and VC. The BC suppressive effects of the OC-LA combination were associated with the modulation of SMYD2–EZH2–STAT3 signaling pathway. A metastasis–clonogenicity animal study model using female nude mice subjected to tail vein injection of MDA-MB-231-Luc TNBC cells also revealed the effective synergy of the combined OC-LA, 5 mg/kg each, compared to their individual therapies and VC. Thus, EVOO cultivars rich in OC with optimal LA content can be useful nutraceuticals for invasive hormone-dependent BC and TNBC progression and metastasis. Full article

Background and Clinical Significance: Orofacial granulomatosis is a rare but often disabling condition potentially associated with inflammatory bowel disease (IBD). Pathogenesis is not well understood, and no disease-specific approved treatment exists to date. Case Presentation: A 26-year-old woman with pan-enteric Crohn’s disease developed buccal swelling and deep oral ulcers histologically confirmed as associated orofacial granulomatosis. Multiple therapies were attempted during her life, including systemic steroids and immunomodulator drugs as Thalidomide, Adalimumab, and Ustekinumab in combination with topical steroid injections and Cyclosporin application, with no or minimal benefit. Only Infliximab showed good efficacy, but it was suspended due to side effects. Following secondary loss of response to Ustekinumab, compassionate treatment with Upadacitinib, a recently developed oral Jak-1 selective inhibitor, resulted in the complete resolution of the oral ulcers. Moreover, after the 12-week induction phase and the transition to 30 mg/daily maintenance dosage, the oral disease remained controlled. Due to the clinical recurrence of Crohn’s disease, Vedolizumab was added as associated treatment, resulting in complete clinical benefit after six months of follow-up. Conclusions: This is a unique case of orofacial granulomatosis associated with pan-enteric Crohn’s disease successfully treated with Upadacitinib. More data are needed to explore its potential benefits in this clinical condition. Full article

People with type 1 diabetes (T1D) need to monitor their blood glucose level frequently and use insulin to regulate it. T1D typically develops in young individuals and requires lifelong insulin injections for glycemic control. High or low blood glucose levels can lead to serious health issues. To address the challenges posed by regular monitoring and manual insulin injections, automated glucose control methods have been developed. Various insulin regimes are used to manage blood sugar levels, such as traditional regimes that involve one or two injections per day or multiple daily injection therapy, which offers more flexibility in the diet and dosage but still requires patients to monitor their carbohydrate intake and insulin injections. A proportional integral derivative (PID) controller is an automated glucose control method that is commonly used in commercial and research settings due to its simplicity and robustness. However, despite its effectiveness, this method can be affected by external factors like food, exercise, and illness. This study proposes to set an individualized observation frequency (OF) per user for the PID controller for blood glucose control in T1D. Optimizing the OF improves the PID controller’s performance, maintaining or elevating median glucose levels. Tuning the OF offers a simple and effective enhancement for the widely used PID controller. Full article

Diabetes mellitus, which comprises a group of metabolic disorders affecting carbohydrate metabolism, is characterized by improper glucose utilization and excessive production, leading to hyperglycemia. The global prevalence of diabetes is rising, with projections indicating it will affect 783.2 million people by 2045. Insulin treatment is crucial, especially for type 1 diabetes, due to the lack of β-cell function. Intensive insulin therapy, involving multiple daily injections or continuous subcutaneous insulin infusion, has proven effective in reducing microvascular complications but poses a higher risk of severe hypoglycemia. Recent advancements in insulin formulations and delivery methods, such as ultra-rapid-acting analogs and inhaled insulin, offer potential benefits in terms of reducing hypoglycemia and improving glycemic control. However, the traditional subcutaneous injection method has drawbacks, including patient compliance issues and associated complications. Nanomedicine presents innovative solutions to these challenges, offering promising avenues for overcoming current drug limitations, enhancing cellular uptake, and improving pharmacokinetics and pharmacodynamics. Various nanocarriers, including liposomes, chitosan, and PLGA, provide protection against enzymatic degradation, improving drug stability and controlled release. These nanocarriers offer unique advantages, ranging from enhanced bioavailability and sustained release to specific targeting capabilities. While oral insulin delivery is being explored for better patient adherence and cost-effectiveness, other nanomedicine-based methods also show promise in improving delivery efficiency and patient outcomes. Safety concerns, including potential toxicity and immunogenicity issues, must be addressed, with the FDA providing guidance for the safe development of nanotechnology-based products. Future directions in nanomedicine will focus on creating next-generation nanocarriers with precise targeting, real-time monitoring, and stimuli-responsive features to optimize diabetes treatment outcomes and patient safety. This review delves into the current state of nanomedicine for insulin delivery, examining various types of nanocarriers and their mechanisms of action, and discussing the challenges and future directions in developing safe and effective nanomedicine-based therapies for diabetes management. Full article

(1) Background: This study aims to evaluate retinal perfusion by optical coherence tomography angiography (OCTA) in pediatric patients with type 1 diabetes mellitus (T1D) without diabetic retinopathy (DR). (2) Methods: Thirty-one patients affected by T1D were enrolled. All participants were evaluated using OCTA. The foveal avascular zone (FAZ) and superficial and deep macular vessel density (VD) were analyzed. The correlation of these parameters with metabolic factors such as body mass index (BMI), glycated hemoglobin (HbA1c), and the type of insulin therapy (multiple daily injections, MDI vs. continuous subcutaneous insulin infusion, CSII) was determined. (3) Results: None of the OCTA parameters were significantly different between the groups. The patients’ HbA1C level did not influence any of the OCTA parameters. The use of MDI tended to reduce the parafoveal and perifoveal deep VD (p = 0.048 and p = 0.021, respectively) compared to CSII. An elevated BMI tended to increase the deep macular (p = 0.005) and perifoveal VD (p = 0.006). (4) Conclusion: VD and FAZ are normal in pubescent children with T1D without signs of DR. Treatment with CSII may be a better choice compared to MDI, as CSII may be protective against retinal microvascular damage. Our results indicate the need for new clinical parameters of glycemic control in addition to HbA1c which could assess the risk of DR. Full article

Basal insulin analogs, typically administered once or twice daily, have been one of the two pillars of the multiple daily injection (MDI) insulin therapy of patients with type 1 diabetes (T1D) for the last twenty years. Recently, once-weekly basal insulin analogs have been developed and are in late-phase clinical trials. One of these analogs is insulin icodec (icodec), appropriately developed to bind reversibly to albumin and to be gradually released into the patient’s circulation. Icodec has been tried mostly in clinical trials of adult patients with type 2 diabetes. A recent phase 3a clinical trial comprising adult patients with T1D was designed to evaluate icodec’s efficacy and safety compared with a daily basal insulin analog (degludec) after a 26-week main phase plus a safety extension of another 26 weeks. Icodec showed non-inferiority to once-daily degludec in glycated hemoglobin (HbA1c) reduction at week 26, and no significant differences in time in range (TIR) (70–180 mg/dL) and in time above range (TAR) (>180 mg/dL). On the other hand, it was associated with increased rates of clinically significant hypoglycemia (blood glucose < 54 mg/dL) and severe hypoglycemia (external assistance need for recovery), remaining either below or close to the internationally recommended targets for hypoglycemia. Another once-weekly insulin analog, basal insulin Fc (BIF), has been investigated in a phase 2 clinical trial comprising adult patients with T1D, with equally promising results. These preliminary data suggest that once-weekly insulin analogs could be of use for some patients with T1D, for example, patients not taking insulin regularly or those who are on MDI and wish for fewer injections. In addition, due to its prolonged mode of action, it could decrease the risk of diabetic ketoacidosis and the need for hospitalization. Additionally, patients with T1D that struggle with wearing diabetes mellitus devices/closed-loop insulin pumps either due to the cost or due to skin issues may also benefit from long-acting insulin. There is increasing evidence of the benefits of adjunctive therapies to insulin in T1D patients, but these therapies are not FDA-approved due to a possible higher risk of diabetic ketoacidosis. These long-acting insulin analogues could be used with adjunctive therapies in selected patients. This review aims to present available data on the mode of action, clinical trial results, and possible benefits of once-weekly insulin analogs for patients with T1D. In addition, it intends to suggest a future research framework for important clinical questions, such as once-weekly insulin analog use and exercise, sick days, or surgery, that will enhance our knowledge regarding this indisputable innovation in insulin management. Full article

Pregnancies complicated by type 1 diabetes (TID) are associated with an increased risk of obstetric and neonatal adverse outcomes. Optimal glycemic control prior to and through pregnancy is crucial to reduce complications. The use of diabetes technology is rapidly increasing. The aim of the study was to investigate the use and effects of diabetes technology in pregnant women with type 1 diabetes. A retrospective cohort study was conducted; 84 women were included in the analysis and were divided into subgroups according to their glucose monitoring method and insulin delivery method. HbA1c values declined during pregnancy in all subgroups with no significant difference between the subgroups. A difference was, however, found in birth weight z-scores. Women using a sensor and an insulin pump had larger babies compared to women without these treatment modalities. The results of the study indicate that diabetes technology, including insulin pumps and/or glucose sensors are not superior to self-monitoring blood glucose measurement and multiple daily injection insulin therapy, which is comforting in the light of the unequal access to health benefits. Full article

Nocturnal hypoglycemia (NH) is a potentially dangerous and underestimated complication of insulin therapy. In this study, we aimed to determine which patterns of nocturnal glucose profiles are associated with NH in patients with type 1 diabetes (T1D) managed with multiple daily insulin injections. A dataset of continuous glucose monitoring (CGM) recordings obtained from 395 adult subjects with T1D was used for modeling. The clustering of CGM data was performed using a hierarchical clustering algorithm. Ten clusters without hypoglycemia and six clusters with NH episode(s) were identified. The differences among the clusters included initial and final glucose levels, glucose change during the night, and the presence of uptrends or downtrends. Post-midnight hyperglycemia was revealed in 5 out of 10 clusters without NH; in patterns with downtrends, initially elevated glucose prevented NH episodes. In clusters with initially near-normal glucose levels and downtrends, most episodes of NH were observed from midnight to 4 a.m.; if glucose was initially elevated, the episodes occurred at 2–4 a.m. or 4–6 a.m., depending on the time of the start of the downtrend. The results demonstrate the diversity of nocturnal glucose profiles in patients with T1D, which highlights the need for a differentiated approach to therapy adjustment. Full article

Glucocorticoids (GCs) are some of the most widely prescribed therapies for treating numerous inflammatory diseases and multiple cancer types. With chronic use, GCs’ therapeutic benefits are concurrent with deleterious metabolic side effects, which worsen when combined with a high-fat diet (HFD). One characteristic of the common Western HFD is the presence of high omega-6 polyunsaturated fatty acids (PUFAs) and a deficiency in omega-3 PUFAs. The aim of this experiment was to determine whether fat composition resulting from HFD affects glucocorticoid-induced alterations in lipid-handling by the liver and skeletal muscle. Male wild-type C57BL/6 mice were randomized into two groups: n-6 (45% fat 177.5 g lard) and n-3 (45% fat 177.5 g Menhaden oil). After 4 weeks on their diets, groups were divided to receive either daily injections of dexamethasone (3 mg/kg/day) or sterile PBS for 1 week while continuing diets. The n-3 HFD diet attenuated adipose and hepatic fatty accumulation and prevented GC-induced increases in liver lipid metabolism markers Cd36 and Fabp. N-3 HFD had little effect on markers of lipid metabolism in oxidative and glycolytic skeletal muscle and was unable to attenuate GC-induced gene expression in the muscle. The present study’s result demonstrated that the change of fat composition in HFD could beneficially alter the fatty acid accumulation and associated lipid metabolism markers in mice treated with dexamethasone. Full article

In this study, we propose a closed-loop insulin administration framework for multiple daily injection (MDI) treatment using a reinforcement learning (RL) agent for insulin bolus therapy. The RL agent, based on the soft actor–critic (SAC) algorithm, dynamically adjusts insulin dosages based on real-time glucose readings, meal intakes, and previous actions. We evaluated the proposed strategy on ten in silico patients with type 1 diabetes undergoing MDI therapy, considering three meal scenarios. The results show that, compared to an open-loop conventional therapy, our proposed closed-loop control strategy significantly reduces glucose variability and increases the percentage of time the glucose levels remained within the target range. In particular, the weekly mean glucose level reduced from 145.34 ± 57.26 mg/dL to 115.18 ± 7.93 mg/dL, 143.62 ± 55.72 mg/dL to 115.28 ± 8.11 mg/dL, and 171.63 ± 49.30 mg/dL to 143.94 ± 23.81 mg/dL for Scenarios A, B and C, respectively. Furthermore, the percent time in range (70–180 mg/dL) significantly improved from 63.77 ± 27.90% to 91.72 ± 9.27% (p = 0.01) in Scenario A, 64.82 ± 28.06% to 92.29 ± 9.15% (p = 0.01) in Scenario B, and 58.45 ± 27.53% to 81.45 ± 26.40% (p = 0.05) in Scenario C. The model also demonstrated robustness against meal disturbances and insulin sensitivity disturbances, achieving mean glucose levels within the target range and maintaining a low risk of hypoglycemia, which were statistically significant for Scenarios B and C. The proposed model outperformed open-loop conventional therapy in all scenarios, highlighting the potential of RL-based closed-loop insulin administration models in improving diabetes management. Full article

We previously published that insulin pump initiation immediately after IV insulin therapy was associated with improved post-surgical glycemic outcomes compared to multiple daily injections (MDI) in pediatric patients following a total pancreatectomy with islet autotransplantation (TPIAT). We investigated metabolic outcomes of this population at one-year post-TPIAT to assess if the improved outcomes in the early pump group were sustained over time. We retrospectively reviewed 40 patients post-TPIAT previously studied at 10-days post-surgery (15 used MDI and 25 used pump therapy immediately post-ICU, and all were discharged on pump therapy). Data analyzed included: demographics, islet equivalents per kilogram (IEQ/kg) transplanted, exogenous insulin use, and baseline vs. one-year (via mixed meal testing) HbA1c, fasting glucose, insulinogenic index, and the area under the curve (AUC) for insulin and c-peptide. More patients were off insulin at one year in the early pump group compared to the MDI group (45% vs. 13%, p = 0.07). Of all patients off insulin, 100% of the early pump users weaned off by six months post-TPIAT compared to 30% of the MDI users. Two known variables associated with favorable insulin outcomes, lower age and higher IEQ/kg, were not significantly different between groups. Fasting glucose was lower in the early pump group compared to the MDI group (median 97 vs. 122 mg/dL, p = 0.003), while AUC c-peptide was greater in early pump users at one-year post-TPIAT but did not reach significance (median 57.0 vs. 50.3 ng/mL × minutes, p = 0.14). Other metabolic outcomes did not differ between groups. Despite lower median age and higher IEQ/kg in the MDI group, the early pump group had a lower fasting glucose. Younger TPIAT age (p = 0.02) and early pump users (p = 0.04) were significantly associated with insulin independence at one year. This study was limited by sample size. Early pump use may have long-term benefits in post-TPIAT endogenous insulin secretion. Full article

Background and Objectives: The expedient resolution of postoperative soft tissue edema is particularly important in hand surgery. Prolonged edema and pain become an obstacle to postoperative rehabilitation, delay return to daily life, and in severe cases, lead to a permanent decrease in range of motion. Based on the common physiology between postoperative hand swelling and complex regional pain syndrome (CRPS), we sought to determine if postoperative mannitol and steroid administration to multiple metacarpal bone fracture patients effectively reduces hand swelling and pain and is beneficial for hand rehabilitation. Materials and Methods: From March 2015 to February 2019, 21 patients who received closed pinning for multiple metacarpal fractures were included in a retrospective cohort study. The control group (n = 11) underwent a routine recovery, while the treatment group (n = 10) received dexamethasone and mannitol injections for five days postoperatively. Serial changes in the degree of pain and fingertip-to-palm distance (FPD) were measured in both groups. The duration from surgery to the initiation of rehabilitation and time to full grip was also compared. Results: Compared to the control, the treatment group showed a faster alleviation of pain scores from the postoperative fifth day (2.91 versus 1.80, p = 0.013), and faster recovery of FPD from postoperative two weeks (3.27 versus 1.90, p = 0.002). Time to physical therapy initiation (6.73 versus 3.80 days, p = 0.002) and full grip achievement (42.46 versus 32.70 days, p = 0.002) were also faster in the treatment group. Conclusions: The steroid-mannitol combination treatment for multiple metacarpal bone fracture patients in the acute postoperative phase promoted the reduction of hand edema and pain, leading to the earlier initiation of physical therapy, rapid improvement in joint motion, and faster achievement of full grip. Full article