Search Results (65)

Background/Objectives: Optimal postprandial glycemic control is crucial to maintain time in range (TIR:3.9–10.0 mmol/L, 70–180 mg/dL) and time in tight range (TITR:3.9–7.8 mmol/L, 70–140 mg/dL), both important to reduce microvascular complications in type 1 diabetes mellitus (T1DM). However, insulin dosing based on carbohydrate counting fails to compensate for delayed hyperglycemia from protein and fat. This study evaluated two advanced insulin dosing algorithms designed to improve postprandial control in adolescents with T1DM. Methods: In this randomized, prospective, double-blind, crossover trial, 58 adolescents with T1DM (median age 15.5 years) were enrolled, all using continuous subcutaneous insulin infusion and a continuous glucose monitoring system in non-automated mode. For two consecutive days, participants consumed standardized mixed meals for breakfast (50 g of carbohydrates, 200 kcal from protein and fat) and received an extended bolus delivered for four hours, based on the Pankowska Equation (PE, i.e., Fat-Protein Units × Insulin-to-Carbohydrate Ratio (ICR)) and the Sieradzki Equation (SE, i.e., 30% × Carbohydrate Units × ICR). Postprandial glucose was monitored for five hours using a glucometer and Continuous Glucose Monitoring (CGM). The primary outcome was the capillary blood glucose level at predefined time points. The secondary outcomes were the frequency of hypoglycemia and glycemic variability parameters. Results: Both methods kept postprandial glucose within the recommended TIR. The SE method provided longer TITR (82.51% vs. 70.49%, p = 0.6281) and fewer hypoglycemic episodes at 180 and 300 min. Glucose levels at 60 min, were higher after PE (136 ± 35.2 mg/dL vs. 124 ± 32.2 mg/dL, p = 0.016). Conclusions: Both algorithms provided effective postprandial control after a mixed meal, but SE achieved a longer TITR and fewer late hypoglycemic events. Full article

Interstitial lung disease associated with connective tissue disease (CTD-ILD) is a severe condition characterized by inflammation and progressive lung fibrosis, with limited treatment options. Previous studies have demonstrated the anti-inflammatory and antifibrotic properties of human umbilical cord-derived mesenchymal stem cells (huMSCs), suggesting their potential as novel therapeutic agents. Therefore, we investigated the dose-dependent therapeutic effects of huMSCs on CTD-ILD. A bleomycin-induced mouse model of interstitial lung disease, in which female C57BL/6J mice developed diffuse pulmonary lesions following continuous subcutaneous infusion of bleomycin, was used. Mice subsequently received intravenous huMSCs at doses of 1.0 × 10³, 1.0 × 10⁴, or 1.0 × 10⁵ cells. The medium dose (1.0 × 10⁴ cells) showed the most pronounced effects on pulmonary fibrosis and collagen deposition, while significantly suppressing pro-inflammatory cytokines, including interleukin-1β and interleukin-6; however, this effect was not consistent across all measured outcomes. The treatment also enhanced beneficial matrix remodeling by downregulating TIMP-1 and upregulating MMP-9 expression. Furthermore, huMSC administration modulated macrophage polarization and inhibited the pro-inflammatory M1 phenotype. These findings highlight the therapeutic potential of huMSCs for CTD-ILD and underscore the importance of dose optimization to balance efficacy and safety. Full article

Background: Doxorubicin, a widely used chemotherapeutic agent, has been shown to increase reactive oxygen species (ROS) levels, disrupting cellular homeostasis not only in cancer cells but also in healthy tissues, particularly in cardiomyocytes, which leads to chemotherapy-induced cardiotoxicity. Therefore, new strategies are continually being explored to mitigate these adverse effects. One such approach is the use of additional substances with cardioprotective properties during doxorubicin therapy. A promising candidate is elabela, a peptide of the apelinergic system, which may exert protective effects against doxorubicin-induced oxidative stress in cardiomyocytes. Objectives: This study aims to evaluate the modulatory effects of elabela on oxidative stress markers, malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in the left ventricle of the myocardium following chronic doxorubicin administration in rats. Material and Methods: 32 male, 12-week-old Sprague-Dawley rats (SPRD) were randomly assigned to four experimental groups. For 28 days, all animals received continuous infusions (2.5 μL/h) via subcutaneously implanted osmotic pumps of 0.9% NaCl or elabela (40 μg/kg body weight/day or 200 μg/kg body weight/day). Simultaneously, animals were injected intraperitoneally 4 times at weekly intervals with 0.9% NaCl or DOX (3.5 mg/kg body weight). Next, the animals were sacrificed, and left ventricular (LV) cardiac tissue was collected for further analysis. MDA and 8-OHdG and elabela level in LV lysate were assessed by ELISA. The Ela expression in LV was quantified by Real-Time PCR. The TUNEL assay, labeled with a 5′-triphosphate strand, was used to assess the degree of apoptosis. Results: DOX treatment decreased both the Ela expression and elabela levels in the LV. Elabela administration at a dose of 200 µg/kg body weight/day significantly decreased ELA levels and Ela expression compared to the control group. The level of 8-OhdG was unexpectedly decreased in the DOX group compared to controls, while elabela treatment at both doses restored 8-OHdG levels observed in the control group. However, TUNEL staining demonstrated that elabela administration at 200 µg/kg body weight/day reduced the number of apoptotic cardiomyocytes compared to the DOX-only group, indicating a protective effect against DOX-induced apoptosis. The lower dose of 40 µg/kg body weight/day showed a moderate, non-significant attenuation of apoptosis. Conclusions: Elabela showed a protective effect against DOX-induced cardiomyocyte apoptosis in the LV by promoting processes that reduce oxidative stress in cardiac cells. Full article

Background and Objectives: Eating disorders are one of the most widespread health concerns, mainly among adolescents. Children and adolescents with type 1 diabetes mellitus (T1DM) have been reported to have a high prevalence of eating disorders. The aim of our study is to evaluate the risk of diabetes-specific eating disorders in children with T1DM using continuous subcutaneous insulin infusion (CSII), with real-time glycemic data from continuous glucose monitoring (CGM). Materials and Methods: Sixty-four patients (aged 7–18 years) completed the Diabetes Eating Problem Survey-Revised (DEPS-R). The DEPS-R is a diabetes-specific self-report questionnaire to assess diabetes-specific compensatory behaviors. Auxological findings, sex, age, age at diagnosis, hemoglobin A1c (HbA1c) levels, and all CGM data were obtained from their medical records. Results: Although the median DEPS-R score was higher in children and adolescents using CSII compared to those using multiple daily injections (MDIs) (14 vs. 11), the difference was not statistically significant (p = 0.302). The risk of diabetes-specific eating disorders was identified in six patients (30%) using CSII and in nine patients (20.4%) using multiple daily injections (p = 0.403). Interestingly, in the subgroup with poor glycemic control (HbA1c > 9%), DEPS-R scores were significantly lower among those using CSII compared to the MDI group. Pearson correlation analysis demonstrated positive associations between DEPS-R scores and diabetes duration, weight SDS, body mass index (BMI), BMI SDS, HbA1c, mean glucose, Glucose Management Indicator (GMI), time above range (TAR) (very high), and coefficient of variation (CV), while a moderate negative correlation was observed with time in range (TIR). Conclusions: This study showed that the treatment of CSII had a beneficial effect on the risk of eating disorders in patients with poor glycemic control. As well, from this perspective, CSII maintains its status as a potentially beneficial therapeutic approach in diabetes management. Full article

In addition to its role in angiotensin II (Ang II) production, chymase exhibits various functions, including activation of latent transforming growth factor beta 1 (TGF-β1) and pro-matrix metalloproteinases (MMPs). However, the extent to which these Ang II-independent functions contribute to pathological conditions remains unclear. In this study, we investigated the Ang II-independent roles of chymase in cardiac remodeling and dysfunction. Eighteen male Syrian hamsters, aged 6 weeks and weighing 90–110 g, were used. Exogenous Ang II was administered to a hamster model that mirrors the human chymase-dependent Ang II production pathway, via subcutaneous osmotic mini pumps (2 mg/kg/day) for 4 weeks. A chymase-specific inhibitor, TY-51469 (10 mg/kg/day), was given daily starting 1 day after commencement of Ang II infusion. Evaluation showed that while systolic blood pressure increased significantly, only diastolic dysfunction developed over time. Ang II treatment led to elevated cardiac expression of chymase, TGF-β1, and MMP-2, and increased the number of chymase-positive mast cells, resulting in notable cardiac hypertrophy and fibrosis. TY-51469 effectively suppressed these molecular changes and improved both cardiac structure and diastolic dysfunction, despite continued Ang II exposure. These results suggest that chymase promotes cardiac remodeling and dysfunction not only through Ang II generation but also by activating profibrotic and matrix-degrading factors, such as TGF-β1 and MMP-2. Full article

Introduction: In healthcare centers with limited resources, or for patients who prefer to make continuous changes in their treatment themselves and do not want to rely solely on technology, intermittent glucose monitoring (isCGM) with an insulin pump is a viable option that warrants further study. Material and methods: prospective single-center study that collected data at 3 months and after isCGM implantation in pediatric patients with Type 1 diabetes, categorized according to their insulin regimen. Results: We found statistically significant differences in the time in range (TIR) between 70 and 180 mg/dl at 3 months after using the sensor (p = 0.017), although these differences were not maintained at 1 year (p = 0.064). When stricter TIRs (70–140 mg/dl) were analyzed, statistically significant differences were observed at 3 months (p = 0.01) and at 1 year (p = 0.018) in favor of patients using CSII. While 75% of the patients in the CSII group had good control with HbA1c < 7% after one year of sensor use, only 34.6% in the MDI group achieved these values. However, the CSII group presented a higher coefficient of variation (62.31% at 3 months and 43.08% at 1 year) (p = 0.02), and a higher number of hypoglycemic episodes (7.38% and 7.32%, respectively) (p = 0.016). The CSII group also had a higher number of capillary blood glucose measurements at the beginning of the study (8.32/day) (p = 0.249), but this number became similar between both groups after one year. Conclusions: We found statistically significant differences in favor of CSII over MDI in terms of metabolic control after one year of isCGM use. However, the TIR values were still below the range considered to be indicative of good control. These findings lead us to question whether CSII should be initially considered in specific cases where HCL is not possible, or if it would be more effective to wait until the patient is ready, or the necessary resources are available to start directly CSII integrated in a closed loop system. Full article

Background/Objectives: Compared to in the general pregnant population, pregnancy in women with type 1 diabetes (T1D) is still associated with an increased number of perinatal complications affecting both the fetus and the mother. The Great Orchestra of Christmas Charity Foundation (GOCCF) program enables the use of continuous subcutaneous insulin infusion (CSII) enhanced by a hypo-stop function and real-time continuous glucose monitoring (rtCGM) during the preconception or early pregnancy period in patients with T1D. This observational study aimed to analyze the association between pregnancy planning and pregnancy outcomes in patients who qualified for the GOCCF program. Methods: Ninety-eight women with T1D, aged 21–41 years, who began using the CSII + rtCGM system at the planning/early pregnancy stage or at a later stage in the case of an unplanned pregnancy, were eligible for this study. We analyzed glucose control, the insulin requirements, the pregestational BMI, the maternal weight gain, the occurrence of preterm births, congenital malformations and the birthweight of newborns. Results: Women who planned their pregnancies had significantly better glycemic control before and throughout the entire pregnancy, and a significantly higher proportion of them achieved a TIR (time in range) > 70% (58.7% vs. 28.9%, p = 0.014) and TAR (time above range) < 25% (65.2% vs. 24.4%, p < 0.001). Their glucose variability at the end of the pregnancy was significantly lower (29.4 ± 5.5 vs. 31.9 ± 5.1, p = 0.030). They also gave birth later, at a mean of 37.8 ± 0.9 weeks compared to 36.9 ± 1.8 weeks in the non-planned group (p = 0.039). Preterm birth occurred in five women (10.4%) who planned their pregnancies and in fifteen women (30%) who did not, with p = 0.031. Conclusions: Pregnancy planning in women with type 1 diabetes (T1D) is associated with better glucose control before conception and throughout the entire pregnancy, resulting in better pregnancy outcomes. Full article

Introduction: Managing glycemic fluctuations in critically ill elderly patients with type 2 diabetes mellitus (T2DM) poses significant challenges. This case report presents a unique scenario in which increased intravenous glucose (Glc) infusion, together with insulin therapy, improved glycemic control and reduced insulin requirements during a septic episode. This finding adds to the scientific literature by suggesting that adequate Glc administration may enhance insulin sensitivity in critically ill T2DM patients. Case report: An 84-year-old female patient with T2DM, hypertension, and chronic renal failure was admitted to the intensive care unit with fever, nausea, loss of appetite, and profound weakness. Laboratory findings revealed severe hyperglycemia, electrolyte imbalances, and markedly elevated inflammatory markers, leading to the diagnosis of decompensated T2DM that was complicated by sepsis. The initial treatment consisted of continuous intravenous (IV) insulin, crystalloid infusions, and broad-spectrum antibiotics. Despite insulin therapy and the absence of nutritional intake, the patient experienced extreme fluctuations in their blood glucose levels, ranging from hyperglycemia to hypoglycemia. Due to persistent glycemic instability, IV Glc infusion was initiated alongside continuous insulin therapy. Paradoxically, increasing Glc infusion administration rate led to a reduction in the required insulin doses and stabilization of blood glucose levels below 10 mmol·L⁻¹. The patient’s C-peptide levels were initially elevated but subsequently decreased following Glc administration as well, suggesting a reduction in endogenous insulin secretion and therefore higher insulin sensitivity. The patient’s clinical condition improved, allowing for the transition to a subcutaneous insulin regime and the initiation of oral feeding. She was later transferred to a general medical ward and discharged without further complications. Conclusions: This case highlights the complex interplay between Glc and insulin in critically ill elderly patients with T2DM during sepsis. The main takeaway is that carefully managed Glc infusion, in conjunction with flexible insulin therapy, can enhance insulin sensitivity and stabilize blood glucose levels without causing further hyperglycemia. Frequent glycemia monitoring and adaptable glycemic management strategies are essential in the ICU to address rapid glycemic fluctuations in this patient population. Full article

Background/Objectives: The association between sexual dysfunction and diabetes is well known, but few studies have investigated its prevalence in type 1 diabetes (T1D). The aim of this study was to evaluate the prevalence of sexual dysfunction in a group of women with T1D, regardless of their age, and to compare its different prevalences in women treated with different insulin regimens. Methods: The population included 77 women affected by T1D, of which 16 were on Multiple Daily Injections (MDI) and 61 on Continuous Subcutaneous Insulin Infusion (45 on Advanced Hybrid Closed Loop System with catheter and 16 on patch pump). All participants completed the Female Sexual Function Index (FSFI), a questionnaire that evaluates several aspects of sexual function. Another questionnaire that evaluated general features, diabetes-specific features and sexual-specific features was proposed to every participant. Results: The overall prevalence of female sexual dysfunction was 49.3%. A correlation was demonstrated between the prevalence of female sexual dysfunction and age; another correlation was found between the prevalence of female sexual dysfunction and dyadic status. No correlation between glycemic control and sexual dysfunction was found. Conclusions: Women with T1D presented a high prevalence of sexual dysfunction, independently from glycometabolic disease control and insulin regimens; on the other hand, a significant correlation was demonstrated with age and dyadic status. Evaluation of sexual function in women with T1D appears to be important in clinical settings independently from disease control. Full article

Background/Objectives: The association between sexual dysfunctions and diabetes is largely known, but few studies investigated its prevalence in Type 1 Diabetes (T1D). The aim of this study was to evaluate the prevalence of sexual dysfunction in a group of men with T1D regardless of their age and to compare the prevalence in men treated with different intensive insulin regimens. Methods: The study population included 68 men affected by T1D, of whom 17 were on Multiple Daily Injections (MDI) and 51 were on Continuous Subcutaneous Insulin Infusion (41 on Advanced Hybrid Closed Loop System with catheters and 10 on patch pumps). All participants completed the International Index of Erectile Function (IIEF-15), which evaluates several domains of sexual function. Another questionnaire that evaluated general features, diabetes-specific features, and sexual-specific features was proposed to every participant. Results: The overall prevalence of erectile dysfunction was 48.5%, and the overall prevalence of a severe grade of erectile dysfunction was 26.5%. Correlations were demonstrated between the prevalence of erectile dysfunction and age and between the prevalence of erectile dysfunction and dyadic status. Age and dyadic status were also correlated with lower scores in several other domains of the IIEF-15 questionnaire. Conclusions: Men with Type 1 Diabetes present a high prevalence of erectile dysfunction, independent of glycometabolic control of the disease and insulin regimens; on the contrary, a great correlation is demonstrated with age and dyadic status. Full article

Background: Treprostinil, which is administered via continuous subcutaneous or intravenous infusion, is a medication applied in the treatment of pulmonary arterial hypertension (PAH). The dose of treprostinil is adjusted on an individual basis for each patient. A number of factors determine how well patients respond to treatment. Objectives: The aim of this study was to identify factors that may influence the clinical response to the dose of treprostinil at 3 months after the start of therapy. Methods: The factors influencing treatment response were analyzed in consecutive PAH patients who started receiving treprostinil treatment. The treatment efficacy was assessed as improvement in 6 min walk distance (6MWD) and WHO functional class (WHO FC), a reduction in N-terminal prohormone of brain natriuretic peptide (NTproBNP), and the percentage of patients achieving low-risk status after 12 months of treatment. Results: A total of 83 patients were included in this analysis. Classification of patients according to the tertiles of treprostinil dose achieved at 3 months after drug inclusion shows that after 12 months of follow-up, the median WHO FC in the highest dose group was lower than that in the intermediate dose group (WHO FC II vs. WHO FC III, p = 0.005), the median NTproBNP was lower (922 pg/mL, vs. 1686 pg/mL, p = 0.036) and 6MWD was longer (300 m vs. 510 m, p = 0.015). The French Noninvasive Criteria (NIFC) scale score was higher (2 vs. 0, p = 0.008), and the Reveal scale score was lower (5.0 vs. 8.5, p = 0.034). In the group of patients who exceeded a dose of 19.8 ng/kg/min within 3 months, an improvement in 6MWD was observed significantly more often after one year of therapy, and they were more likely to show an increase in NIFC scale scores after one year of therapy than the group of patients who received the lower dose (65% vs. 30%, p = 0.02). In the group of patients younger than 50 years of age, a statistically significant correlation was observed between the dose of treprostinil achieved after three months of treatment and the parameters assessed after 12 months of treatment, including WHO FC, 6MWD, and NIFC prognostic scale scores (all p < 0.05). Conclusions: The clinical effect of treatment is critically dependent on the rapid escalation of the treprostinil dose during the first three months of treatment. Full article

Background: The management of type 1 diabetes in pregnancy with new technologies is challenging. Sometimes the complexity of new-generation systems such as “continuous subcutaneous insulin infusion, CSII” and patient or provider preference do not allow their use, so women with type 1 diabetes in pregnancy continue to be treated with subcutaneous multiple-injection insulin therapy using pens. Smart insulin pens are new tools that allow for data collection on insulin dose and time of administration and have additional connectivity features. Objective: To retrospectively describe the use of a smart insulin pen coupled with rt-CGM (InPen^TM system) in three pregnancies complicated by type 1 diabetes. Methods: Participants used the InPen^TM system in pregnancy and consented to analysis of glycaemic data and pregnancy outcome. Results: An increase in pregnancy specific time-in-range glucose was observed in the three patients related to the duration of insulin action, insulin sensitivity factors, and a pre-set target glucose range for pregnancy. No diabetic ketoacidosis or severe hypoglycaemia occurred. Conclusions: We describe practical considerations in three pregnant patients with type 1 diabetes where the InPen^TM system was used with suggestive improvements in the time-in-range. Full article

Background and Objectives: The rapid growth of the number of advanced Parkinson’s disease (PD) patients has caused a significant increase in the use of device-aided therapies (DATs), including levodopa–carbidopa intestinal gel (LCIG) and continuous subcutaneous apomorphine infusion (CSAI). The objective of this study was to evaluate patients’ satisfaction and the factors influencing preferences for CSAI and LCIG. Materials and Methods: The research focused on individuals diagnosed with advanced PD undergoing DAT at the Neurology Department of the University Hospital in Katowice. A telephone survey conducted between June and July 2024 evaluated the experiences of patients with LCIG and CSAI. The Parkinson’s Disease Questionnaire (PDQ-8) and the Stress Scale for Family Caregivers (BSFC-s) were applied. Based on medical record data comprising reasons for the exclusion of individuals, disease-related and treatment data were collected. Results: Among the original cohort of 64 patients, 50 completed the survey, including 31 who might choose between infusion therapies. The average patient ages were 70.6 ± 4.7 (CSAI) and 71.2 ± 7.2 years (LCIG), with disease durations of 15 (IQR: 12–19) and 18 (IQR: 13–19) years, respectively. LCIG patients presented higher PDQ-8 scores (20 (IQR: 13–27) vs. 13 (IQR: 6–19), p = 0.008), and higher BSFC-s scores (19 (IQR: 12–21) vs. 9 (IQR: 2.5–13), p = 0.011). Furthermore, significant factors influencing patient preferences included fear of surgery (75% vs. 36.8%, p = 0.043) and concerns about DAT safety (83.3% vs. 47.4%, p = 0.049). Conclusions: LCIG and CSAI therapies offer benefits and disadvantages, with safety concerns and fear of surgery seeming to be decisive in the decision-making process. Full article

Type 1 diabetes (T1D) is a complex chronic condition that places young adults aged 18–31 years at high risk for general and diabetes-related distress and poor cardiovascular health. Both general and diabetes distress are linked to higher A1C, a known risk factor for cardiovascular disease (CVD). The purpose of this cross-sectional quantitative descriptive study was to examine the associations between distress symptoms (general and diabetes) and cardiovascular health while considering covariates in young adults ages 18–31 years with T1D. One-hundred and sixty-five young adults with T1D, recruited from specialty clinics through two major health systems and online platforms, completed a demographic and clinical survey along with the 8-item PROMIS Emotional Distress Scale and 17-item Diabetes Distress Scale. Higher diabetes distress and higher general emotional distress were associated with lower cardiovascular health scores. Associations remained statistically significant after adjusting for age, T1D duration, sex at birth, race, and continuous subcutaneous insulin infusion. In young adults with type 1 diabetes, addressing both diabetes and general emotional distress may be important to improve cardiovascular health. However, longitudinal and experimental studies are needed to clarify underlying mechanisms and evaluate the effectiveness of interventions like cognitive behavioral therapy. Full article

Australian children with diabetes commonly struggle to achieve optimal glycaemic control, with minimal improvement observed over the past decade. The scarcity of research in the rural and regional Australian context is concerning, given high incidence rates and prominent barriers to healthcare access in these areas. We conducted a retrospective audit of 60 children attending a regional Australian paediatric diabetes service between January 2020 and December 2023. The majority of patients had type 1 diabetes (n = 57, 95.0%); approximately equal numbers were managed with continuous subcutaneous insulin infusion (CSII) pumps vs. multiple daily injections (MDIs), whilst 88.3% (n = 53) also utilised continuous glucose monitoring (CGM). The mean age at last visit was 14.0 years (SD, 3.4), mean diabetes duration 5.8 years (SD, 4.6), and mean HbA1c level 8.1% (65.3 mmol/mol); only 36.8% achieved the national target of 7.5% (58 mmol/mol). Mean BMI-SDS was 0.8 (SD, 1.0); almost half (n = 27, 45.0%) were overweight or obese. Many patients had mental health conditions (31.7%), which were associated with higher hospitalisation rates (p = 0.007). The attendance rate was 83.2%, with a mean of 3.3 clinic visits per year (SD, 0.7); higher attendance rates were associated with increased CGM sensor usage (r = 0.395, p = 0.007 Overall, the diabetes service performed similarly to other clinics with regards to glycaemic control. Whilst achieving treatment targets and addressing comorbidities remains a challenge, the decent attendance and the high uptake of healthcare technologies is commendable. Further efforts are needed to improve diabetes management for this regional community. Full article