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8 pages, 483 KB  
Case Report
Case Report of Overlap of Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State in a 5-Year-Old with New-Onset Type 1 Diabetes Mellitus: Diagnostic and Management Considerations
by Filippos Filippatos, Georgios Themelis, Maria Dolianiti, Christina Kanaka-Gantenbein and Konstantinos Kakleas
Reports 2026, 9(1), 27; https://doi.org/10.3390/reports9010027 - 16 Jan 2026
Viewed by 305
Abstract
Background and Clinical Significance: Overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) in children is a rare but life-threatening metabolic emergency. The coexistence of hyperosmolality and ketoacidosis increases neurologic vulnerability and complicates fluid and insulin management. Early identification and osmolality-guided therapy [...] Read more.
Background and Clinical Significance: Overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) in children is a rare but life-threatening metabolic emergency. The coexistence of hyperosmolality and ketoacidosis increases neurologic vulnerability and complicates fluid and insulin management. Early identification and osmolality-guided therapy are essential to prevent cerebral edema and other complications. This case describes a 5-year-old boy with new-onset type 1 diabetes mellitus (T1D) presenting with DKA/HHS overlap two weeks after influenza vaccination—an unusual temporal association without proven causality. Case Presentation: A previously healthy 5-year-old presented with progressive polyuria, polydipsia, nocturnal enuresis, fatigue, and drowsiness. Two weeks earlier, he had received the influenza vaccine. Examination revealed moderate dehydration without Kussmaul respiration or altered consciousness. Laboratory evaluation showed glucose 45.9 mmol/L (826 mg/dL; reference 3.9–7.8 mmol/L), venous pH 7.29 (reference 7.35–7.45), bicarbonate 12 mmol/L (reference 22–26 mmol/L), moderate ketonuria, and measured serum osmolality 344 mOsm/kg (reference 275–295 mOsm/kg), fulfilling diagnostic criteria for DKA/HHS overlap. After an initial 20 mL/kg 0.9% NaCl bolus, fluids were adjusted to maintenance plus approximately 10% deficit using 0.45–0.75% NaCl according to sodium/osmolality trajectory. Intravenous insulin (approximately 0.03–0.05 IU/kg/h) was initiated once blood glucose no longer decreased adequately with fluids alone and had stabilized near 22.4 mmol/L (≈400 mg/dL). Dextrose was added when glucose reached 13.9 mmol/L (250 mg/dL) to avoid rapid osmolar shifts. Hourly neurological and biochemical monitoring ensured a glucose decline of 2.8–4.2 mmol/L/h (50–75 mg/dL/h) and osmolality decrease ≤3 mOsm/kg/h. The patient recovered fully without cerebral edema or neurologic sequelae. IA-2 antibody positivity with low C-peptide and markedly elevated HbA1c confirmed new-onset T1D. Conclusions: This case highlights the diagnostic and therapeutic challenges of pediatric DKA/HHS overlap. Osmolality-based management, conservative insulin initiation, and vigilant monitoring are crucial for preventing complications. The temporal proximity to influenza vaccination remains incidental. Full article
(This article belongs to the Section Paediatrics)
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25 pages, 4567 KB  
Article
Systematic Development and Characterization of Enzyme-Free, Borax-Crosslinked Microneedles for Glucose-Responsive Insulin Delivery and In Vivo Glycemic Mitigation
by Cuc Thi Dinh, Linh Phuong Nguyen, Uyen Thu Pham, Anh Mai Nguyen, Hanh Thi My Do, Toan Quoc Tran, Phuong Duc Luu, Tien Duy Doan, Mo Thi Hong Bui and Duong Thanh Nguyen
Pharmaceutics 2025, 17(12), 1578; https://doi.org/10.3390/pharmaceutics17121578 - 8 Dec 2025
Viewed by 594
Abstract
Background: Conventional insulin injections cannot mimic physiological pancreatic function and often lead to dangerous hypoglycemic events that glucose-responsive systems aim to prevent. Glucose-responsive microneedles (MNs) offer a promising closed-loop alternative. We developed an enzyme-free, glucose-responsive MN patch composed of a PVA/Dextran hydrogel dynamically [...] Read more.
Background: Conventional insulin injections cannot mimic physiological pancreatic function and often lead to dangerous hypoglycemic events that glucose-responsive systems aim to prevent. Glucose-responsive microneedles (MNs) offer a promising closed-loop alternative. We developed an enzyme-free, glucose-responsive MN patch composed of a PVA/Dextran hydrogel dynamically crosslinked with borax, and evaluated its performance, biosafety, and in vivo efficacy. Methods: MNs were fabricated from PVA/Dextran via micromolding and crosslinked with borax. The formulation was systematically optimized based on mechanical properties and glucose-responsive release kinetics. Physicochemical properties, biosafety (cytotoxicity, skin barrier recovery, boron leaching), and in vivo efficacy in a type 1 diabetic mouse model were evaluated in comparison to a subcutaneous (SC) insulin injection. Results: The optimized MNs showed robust mechanics (per-needle fracture force approximately 1.0 N) for reliable skin penetration. The system demonstrated clear glucose sensitivity, with a release flux ratio ≥1.5 between hyperglycemic (e.g., 400 mg·dL−1) and normoglycemic (100 mg·dL−1) conditions and exhibited excellent reversibility under alternating glucose levels. The patch was highly biocompatible, with >95% cell viability, the only transient skin barrier disruption that fully recovered within 24 h, and had low boron release from patches in vitro. In vivo, the optimized sI-MN patch demonstrated a sustained, glucose-responsive release profile, maintaining blood glucose in diabetic mice near 100 mg·dL−1 for approximately 8 h. This pharmacokinetic profile contrasts markedly with the rapid hypoglycemic nadir and rebound hyperglycemia observed with a standard subcutaneous insulin bolus, highlighting the patch’s potential for mitigating hypoglycemia. Conclusions: The enzyme-free PVA/Dextran/borax MN patch enables autonomous, glucose-responsive insulin delivery. It provides more stable and safer glycemic control than conventional injections by mitigating the risk of hypoglycemia. By mitigating the hypoglycemic risk associated with bolus injections, this systematically optimized platform represents a potential step toward a safer, patient-friendly diabetes therapy, though significant challenges in duration and dose scaling remain. Full article
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13 pages, 633 KB  
Article
Comparison of Oral Antidiabetic Medications and Insulin Therapy for Glucocorticoid-Induced Hyperglycemia in Patients with Autoimmune Diseases
by Shinichiro Ueno, Masataka Tajima, Kiyomi Saito, Masayuki Yoshikawa, Takeo Isozaki, Hitoshi Sato and Erika Sugiyama
J. Clin. Med. 2025, 14(24), 8642; https://doi.org/10.3390/jcm14248642 - 5 Dec 2025
Viewed by 639
Abstract
Background: Glucocorticoid-induced hyperglycemia (GCIH) is a common adverse effect of glucocorticoid (GC) therapy. Although evidence on oral antidiabetic medications (OADMs) for GCIH is emerging, direct comparisons with insulin therapy remain limited. This study aimed to compare the efficacy and safety of OADMs [...] Read more.
Background: Glucocorticoid-induced hyperglycemia (GCIH) is a common adverse effect of glucocorticoid (GC) therapy. Although evidence on oral antidiabetic medications (OADMs) for GCIH is emerging, direct comparisons with insulin therapy remain limited. This study aimed to compare the efficacy and safety of OADMs and sliding scale insulin (SSI) in patients with autoimmune diseases who developed GCIH. Methods: We retrospectively analyzed 97 patients who developed GCIH during GC therapy equivalent to ≥20 mg/day of prednisolone. Patients were classified into SSI-only (n = 41), OADM (n = 31), and basal–bolus/basal or bolus insulin (BBI/BI) (n = 25) groups. The primary endpoint was mean preprandial blood glucose (BG), adjusted for patient characteristics. Secondary outcomes included hospital stay, hypoglycemia, insulin use, and glycated hemoglobin. Results: In univariate analysis, the mean preprandial BG levels during the treatment period were significantly associated with the mean initial preprandial BG levels. Adjusted mean preprandial BG during treatment did not differ significantly between the OADM and SSI-only groups, whereas the BBI/BI group had higher pre-breakfast BG (p = 0.016). Among first-time GC users, those in the OADM group using cyclophosphamide had significantly lower fasting BG than non-users (p = 0.011). Conclusions: In patients with autoimmune diseases receiving ≥20 mg/day GC, OADM provided glycemic control comparable to SSI with similar hypoglycemia risk. Early preprandial BG levels during the first 3 days of GC therapy may help predict glycemic outcomes. Prospective studies with standardized regimens are needed to optimize GCIH management. Full article
(This article belongs to the Section Pharmacology)
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15 pages, 2207 KB  
Article
The Impact of Two Different Insulin Dose Calculation Methods on Postprandial Glycemia After a Mixed Meal in Children with Type 1 Diabetes: A Randomized Study
by Magdalena Dymińska, Emilia Kowalczyk-Korcz, Katarzyna Piechowiak and Agnieszka Szypowska
Nutrients 2025, 17(20), 3287; https://doi.org/10.3390/nu17203287 - 20 Oct 2025
Viewed by 1628
Abstract
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 [...] Read more.
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
(This article belongs to the Section Nutrition and Diabetes)
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13 pages, 1926 KB  
Article
Performing Dual Glucose Clamp Experiments in Sedated Farm Swine: A Practical Method
by Marc C. Torjman, Winston C. Hamilton, Katherine Dillon, Channy Loeum and Jeffrey I. Joseph
Methods Protoc. 2025, 8(5), 118; https://doi.org/10.3390/mps8050118 - 2 Oct 2025
Viewed by 825
Abstract
The hyperinsulinemic–euglycemic clamp technique is considered the gold standard for measuring insulin sensitivity in large animals. We developed a practical method for conducting concurrent glucose clamp experiments in a pair of sedated farm swine positioned in a sling. Descriptions of customized equipment and [...] Read more.
The hyperinsulinemic–euglycemic clamp technique is considered the gold standard for measuring insulin sensitivity in large animals. We developed a practical method for conducting concurrent glucose clamp experiments in a pair of sedated farm swine positioned in a sling. Descriptions of customized equipment and central venous access surgical procedures for blood collection are provided. Personnel functions are described for execution of the clamp protocol. A total of 24 hyperinsulinemic–euglycemic clamp studies were performed over 6 weeks. Infusaports remained functional for 1454 blood samples. There were three CSII catheter occlusions during bolus administration, and the swine showed no signs of infection or disease. IM telazol at 1.0 mg/kg, administered 1–2 h prior (mean of 3.26 mL ± 1.59) was effective in keeping animals comfortable. SpO2 and heart rate remained within normal ranges. Means ± SD total infused volumes for octreotide, 10% dextrose, and saline were 9.7 ± 0.93 mL, 2328.0 ± 672.8 mL, and 690.3 ± 206.8 mL. Mean blood glucose was maintained between 75.7 and 87.8 mg/dL (CV 3.17%) for the 24 experiments. The GIR infusion rate peaked between 15 and 60 min after insulin bolusing, with insulin Cmax of 108.5 pmol/L and tmax at 10 min. All aspects of the protocol were effectively carried out. The animals remained in good health, and the implanted infusion ports remained patent for over 700 blood draws per animal. This method could potentially reduce the number of animals used and the costs of other similar experiments. Full article
(This article belongs to the Section Biomedical Sciences and Physiology)
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11 pages, 463 KB  
Article
Impact of the Menstrual Cycle on Glycemic Control in Women with Type 1 Diabetes and the Potential Role of AHCL Systems
by Angelo Milioto, Chiara Gulisano, Giordano Spacco, Giulia Siri, Benedetta Caccia, Maria Grazia Calevo, Nicola Minuto, Davide Carlo Maggi, Marta Bassi and Francesco Cocchiara
Diabetology 2025, 6(6), 53; https://doi.org/10.3390/diabetology6060053 - 6 Jun 2025
Viewed by 4890
Abstract
Background/Objectives: Hormonal fluctuations during the menstrual cycle can affect glycemic control in women with type 1 diabetes (T1D), especially during the luteal phase, when increased insulin resistance may lead to prolonged hyperglycemia. Advanced Hybrid Closed-Loop (AHCL) systems could help manage these hormone-driven [...] Read more.
Background/Objectives: Hormonal fluctuations during the menstrual cycle can affect glycemic control in women with type 1 diabetes (T1D), especially during the luteal phase, when increased insulin resistance may lead to prolonged hyperglycemia. Advanced Hybrid Closed-Loop (AHCL) systems could help manage these hormone-driven fluctuations. This study aimed to assess glycemic control across menstrual phases and explore the role of AHCL systems in counteracting the related glucose variability. Methods: A retrospective study was conducted including women with T1D and regular menstrual cycles (study group) and women on estroprogestin therapy (control group). Each group was subdivided by insulin delivery method (AHCL vs. non-AHCL). Glycemic metrics and insulin requirements were compared between the follicular and luteal phases, and between groups. Results: The study included 94 women (62 in the study group, 32 in the control group). In the study group, glycemic control worsened during the luteal phase, with increased average glucose, glycemic variability, and time above range > 250 mg/dL (+0.93%, p = 0.03) and reduced time in range 70–180 mg/dL. These changes were more pronounced among AHCL users, who also showed a significant increase in bolus insulin. No phase-related differences were observed in the control group or among non-AHCL users. Significantly higher insulin needs during the follicular phase were found in the study group compared with the controls. Conclusions: This study confirmed a worsening in glycemic control in women affected by T1D during the luteal phase of the menstrual cycle, suggesting a need for more tailored management. The clear efficacy of AHCL systems in counteracting hormone-related glycemic fluctuations has not been proved, highlighting the need for further research in larger, more homogeneous cohorts. Full article
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11 pages, 230 KB  
Article
Prevalence and Characteristics of Patients with Cystic Fibrosis-Related Diabetes in Croatia
by Lora Stanka Kirigin Biloš, Maja Baretić, Andrea Vukić Dugac, Krešimir Schoenwald, Ivan Bambir, Duška Tješić Drinković, Nevena Krnić and Velimir Altabas
Life 2025, 15(5), 815; https://doi.org/10.3390/life15050815 - 20 May 2025
Viewed by 1017
Abstract
This study investigated the prevalence of cystic fibrosis-related diabetes (CFRD) in the Croatian cystic fibrosis (CF) population, the age at diagnosis, insulin requirements, and the relationship between age at diagnosis and other clinical parameters. Medical records from 152 patients with genetically and laboratory-confirmed [...] Read more.
This study investigated the prevalence of cystic fibrosis-related diabetes (CFRD) in the Croatian cystic fibrosis (CF) population, the age at diagnosis, insulin requirements, and the relationship between age at diagnosis and other clinical parameters. Medical records from 152 patients with genetically and laboratory-confirmed CF were reviewed through to 2025. The American Diabetes Association criteria were used to diagnose CFRD. Anthropometric and clinical data were collected from the latest medical records. A total of 17 out of 152 patients had CFRD, with a prevalence of 4.8% in the paediatric population (4/84) and 19.1% in adults (13/68). The median age of CFRD diagnosis was 14 years (range 9–22 years, SD = 3.95). Thirteen patients used insulin: one used bolus only, seven used basal-bolus multiple daily injections, and five used insulin pumps. The average total daily insulin (TDI) per kilogram (kg) body weight was 0.447 U/kg (SD = 0.429). The age at CFRD diagnosis was positively correlated with the body mass index (BMI) (p = 0.029). Patients requiring insulin by age 15 had higher TDI and were more likely to have CF liver disease (p = 0.027, p = 0.037, respectively). The prevalence of CFRD and age at diagnosis aligned with previous studies. Patients diagnosed at a younger age and requiring insulin earlier had lower BMIs, likely due to a faster decline in beta cell function and earlier onset of insulinopenia. Full article
(This article belongs to the Special Issue Cystic Fibrosis: A Disease with a New Face)
13 pages, 2038 KB  
Article
Continuous Intravenous Insulin Infusion in Patients with Diabetes Mellitus After Coronary Artery Bypass Grafting: Impact on Glycemic Control Parameters and Postoperative Complications
by Alexey N. Sumin, Natalia A. Bezdenezhnykh, Dmitry L. Shukevich, Andrey V. Bezdenezhnykh and Olga L. Barbarash
J. Clin. Med. 2025, 14(9), 3230; https://doi.org/10.3390/jcm14093230 - 6 May 2025
Viewed by 1369
Abstract
Objectives: This study compared the efficacy of continuous insulin infusion therapy (CIT) versus standard bolus insulin therapy in maintaining optimal perioperative glycemic control in patients with type 2 diabetes mellitus (T2DM) undergoing coronary artery bypass grafting (CABG), focusing on postoperative outcomes. Methods: In [...] Read more.
Objectives: This study compared the efficacy of continuous insulin infusion therapy (CIT) versus standard bolus insulin therapy in maintaining optimal perioperative glycemic control in patients with type 2 diabetes mellitus (T2DM) undergoing coronary artery bypass grafting (CABG), focusing on postoperative outcomes. Methods: In this single-center, open comparative study, 214 T2DM patients were selected from 1372 CABG cases (2016–2018) and divided into CIT (n = 28) and bolus therapy (n = 186) groups. Both groups were matched for sex, age, smoking status, body mass index, functional class of angina or heart failure, surgical characteristics and preoperative HbA1c. The target glucose range was 7.8–10 mmol/L (140–180 mg/dL), consistent with current guidelines. Glycemic control was assessed through frequent postoperative measurements, with particular attention to glucose variability and hypoglycemic events. Results: The CIT group demonstrated superior glycemic control, with significantly lower median glucose levels at 7, 8, 10, 12, and 13 h post-CABG (p < 0.05). Glycemic variability was reduced by 32% in the CIT group (p = 0.012), and the incidence of hypoglycemia (<3.9 mmol/L) was 3.6% versus 8.1% in the bolus group. While overall complication rates were similar, the CIT group had 0 cases of stroke, myocardial infarction, or wound infections versus 2.7%, 3.2%, and 5.9%, respectively, in the bolus group. Logistic regression confirmed that each 1 mmol/L increase in first-day glucose levels independently predicted both significant (OR 1.20, 95% CI 1.06–1.36) and serious complications (OR 1.16, 95% CI 1.03–1.30). Conclusions: CIT provided more stable postoperative glycemic control with reduced variability and hypoglycemia risk in T2DM patients after CABG. Although underpowered to detect differences in rare complications, our findings suggest CIT may improve outcomes. These results warrant validation in larger randomized trials. Full article
(This article belongs to the Special Issue Cardiovascular Disease and Diabetes: Management of Risk Factors)
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11 pages, 3366 KB  
Case Report
Type I Diabetes—A Rare Adverse Event Described in Patients Receiving Immunotherapy Versus a Side Effect from SARS-CoV-2 Infection
by Raluca-Ileana Pătru, Miruna Ghigeanu, Maria-Alexandra Barbu, Andreea Iuliana Ionescu and Antone-Iordache Ionuț-Lucian
Reports 2025, 8(1), 31; https://doi.org/10.3390/reports8010031 - 14 Mar 2025
Viewed by 1425
Abstract
Background and Clinical Significance: Lung cancer, a leading cause of global cancer diagnoses, maintains the highest mortality risk despite advances in treatment. Immunotherapy agents, such as anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1), have revolutionized care for non-small cell lung cancer (NSCLC). However, the [...] Read more.
Background and Clinical Significance: Lung cancer, a leading cause of global cancer diagnoses, maintains the highest mortality risk despite advances in treatment. Immunotherapy agents, such as anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1), have revolutionized care for non-small cell lung cancer (NSCLC). However, the success is tempered by the emergence of immune-mediated adverse reactions, including the rare onset of type I diabetes. The incidence of diabetes mellitus increased during the SARS-CoV-2 pandemic. While there are several cases of new-onset diabetes after COVID-19 and COVID-19 vaccination, no case of new-onset type 1 diabetes after COVID-19 was described in an immune checkpoint inhibitor (ICI)-treated patient. Case Presentation: A 57-year-old male with stage IV NSCLC (brain and liver metastases) who had been treated with nivolumab for 4 years appeared positive for SARS-CoV-2 infection at a routine check. After two weeks, he was admitted to our clinic with severe fatigue, hyperglycemia, hyponatremia, and hyperkalemia. HbA1c level was normal and serum peptide C was undetectable. Nivolumab treatment was ceased, and the patient became fully dependent on basal–bolus insulin. After 3 months, the patient showed a complete imagistic remission. Conclusions: The case presented significant challenges due to the unclear etiology of newly onset diabetes and the uncommon age at which type 1 diabetes is developed. The outcome suggests that anti-PD-1 and SARS-CoV-2 infection can act synergistically. Full article
(This article belongs to the Section Oncology)
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10 pages, 196 KB  
Case Report
Advancing Telemedicine Using Smart Insulin Pens with Continuous Glucose Monitoring and Telecommunication Systems: A Case Series
by Lakshmi G. Singh, Chikara Gothong, Garrett I. Ash, Reynier Hernandez and Elias K. Spanakis
J. Clin. Med. 2025, 14(6), 1794; https://doi.org/10.3390/jcm14061794 - 7 Mar 2025
Cited by 1 | Viewed by 2885
Abstract
Background: Multiple daily injections (MDIs) have been a mainstay for insulin delivery by persons with type 1 diabetes mellitus (T1DM). “Smart” insulin pens (SIPs) offer several advantages over traditional insulin pens, such as a memory function, bolus calculator, and reminders for patients to [...] Read more.
Background: Multiple daily injections (MDIs) have been a mainstay for insulin delivery by persons with type 1 diabetes mellitus (T1DM). “Smart” insulin pens (SIPs) offer several advantages over traditional insulin pens, such as a memory function, bolus calculator, and reminders for patients to take their insulin. SIPs can integrate with CGM, allowing for the collection of accurate insulin and glucose data, which can integrate into combined reports. Using these technologies along with telecommunication modalities provides an infrastructure to improve the way in which healthcare can be delivered to those with diabetes. Methods: Four cases of uncontrolled T1DM managed by MDIs (and not insulin pumps) and deemed to have plateaued in their management were selected to retrospectively review to identify potential advantages of SIP/CGM along with telemedicine as a method of care delivery. Results: This case series revealed potential benefits of this model of care delivery, such as the ability to identify dysglycemia patterns not discernible prior to the use of SIP/CGM, use combined reports as a visual education tool to provide targeted insulin and dietary education, and improve patient engagement in diabetes self-care behaviors. Conclusions: We described the benefits of using SIPs and CGM technologies along with telecommunication solutions, as a novel concept for a comprehensive telemedicine system, to improve management of glycemic control and diabetes self-management capabilities. Full article
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14 pages, 1203 KB  
Article
Metabolic and Hormonal Responses to Isomaltulose Ingestion Before or During Sustained Submaximal Exercise in Adults with Type 1 Diabetes Using Automated Insulin Delivery Systems
by Olivia M. McCarthy, Merete Bechmann Christensen, Sandra Tawfik, Kasper Birch Kristensen, Bolette Hartmann, Jens Juul Holst, Signe Schmidt, Kirsten Nørgaard and Richard M. Bracken
Nutrients 2024, 16(23), 4098; https://doi.org/10.3390/nu16234098 - 28 Nov 2024
Cited by 3 | Viewed by 3763
Abstract
Objectives: This article compares metabolic, pancreatic, and gut-derived hormone responses to isomaltulose ingestion, before versus during submaximal sustained exercise, in adults with type 1 diabetes (T1D) using automated insulin delivery systems. Methods: In a randomized, cross-over trial, eight participants with T1D being treated [...] Read more.
Objectives: This article compares metabolic, pancreatic, and gut-derived hormone responses to isomaltulose ingestion, before versus during submaximal sustained exercise, in adults with type 1 diabetes (T1D) using automated insulin delivery systems. Methods: In a randomized, cross-over trial, eight participants with T1D being treated with automated insulin pumps (five females, age: 47 ± 16 years, BMI: 27.5 ± 3.8 kg·m2, diabetes duration: 23 ± 11 years, HbA1c: 8.3 ± 0.9 [67.5 ± 9.5]% [mmol/mol]) attended the laboratory on two separate occasions and consumed an isocaloric amount of isomaltulose as either (1) a single serving (0.75g CHO·kg−1 BM) with a 25% reduction in bolus insulin 90 min before 45 min of cycling (PEC) or (2) three separate isocaloric servings (0.25g CHO·kg−1 BM each) without bolus insulin during exercise (DEC). Plasma glucose (PG), gut incretins (GLP-1 and GIP), pancreatic glucagon, exogenous insulin, and whole-body fuel oxidation rates were determined. Data were treated via a two-way repeated measures ANOVA, with p ≤ 0.05 accepted as significant. Results: PG concentrations throughout exercise were higher and less variable with DEC compared to PEC. The exercise-induced change in PG was directionally divergent between trials (PEC: ∆ − 3.2 ± 1.2 mmol/L vs. DEC: ∆ + 1.7 ± 1.5 mmol/L, p < 0.001), changing at a rate of −0.07 ± 0.03 mmol/L/min with PEC and +0.04 ± 0.03 mmol/L/min with DEC (p < 0.001 between conditions). Throughout the exercise period, GLP-1, GIP, glucagon, and total insulin concentrations were lower with DEC (all p ≤ 0.02). The oxidation rates of carbohydrates were lower (p = 0.009) and of lipids were greater (p = 0.014) with DEC compared to PEC. Conclusions: The consumption of smaller servings of isomaltulose during, rather than as a single isocaloric serving before, submaximal sustained exercise provided (i) a better glycemic protective effect, (ii) a lesser push on pancreatic and gut-mediated glucoregulatory hormones, and (iii) a lower reliance on whole-body carbohydrate oxidation. Such information serves to remind us of the potential importance of nutrition for modulating the metabolic fate of an acute bout of exercise and may help inform best practice guidelines for exercise management in the T1D-sphere. Full article
(This article belongs to the Special Issue Advances in Nutrition and Lifestyle Interventions for Type 1 Diabetes)
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13 pages, 605 KB  
Article
The Effect of the Oral Contraceptive Pill on Acute Glycaemic Response to an Oral Glucose Bolus in Healthy Young Women: A Randomised Crossover Study
by Julia M. E. Cree, Niamh M. Brennan, Sally D. Poppitt and Jennifer L. Miles-Chan
Nutrients 2024, 16(20), 3490; https://doi.org/10.3390/nu16203490 - 15 Oct 2024
Cited by 1 | Viewed by 5692
Abstract
Background/Objective: The oral contraceptive pill (OCP) is widely used by women worldwide, yet the influence of the OCP on carbohydrate metabolism remains under-investigated, with existing studies being few and largely cross-sectional. The study objective was to assess, for the first time, the effect [...] Read more.
Background/Objective: The oral contraceptive pill (OCP) is widely used by women worldwide, yet the influence of the OCP on carbohydrate metabolism remains under-investigated, with existing studies being few and largely cross-sectional. The study objective was to assess, for the first time, the effect of the combined OCP on postprandial glycaemic response to an oral glucose bolus, using a randomised crossover design. Methods: The effect of a combined monophasic OCP phase on glucose homeostasis and metabolic profile was investigated in 21 healthy young women, who were regular users of either androgenic or anti-androgenic OCP formulations. Plasma glycaemic markers (glucose, insulin and C-peptide) were assessed prior to a 60 g glucose drink (fasting) and for a further 4 h postprandially; once during the “active” (hormone-containing) pill phase and once during the “inactive” (hormone-free) pill phase of the OCP usage cycle. Results: Despite no change in fasting values, in androgenic pill users, postprandial glucose and insulin responses to an oral glucose bolus were ~100% and ~50% greater, respectively, during the active versus inactive phase. In contrast, in anti-androgenic pill users there was no significant change in response between the two OCP usage cycle phases. Conclusions: These findings highlight an acute, but potentially detrimental, influence of the combined OCP on glucose homeostasis, particularly in users of formulations containing androgenic progestogens. Given the high global prevalence of OCP use and increasingly common prolonged active pill regimens, which may continue for months, years or even decades, potential cumulative effects of such changes on metabolic risk demand further investigation. Full article
(This article belongs to the Section Nutrition in Women)
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25 pages, 2856 KB  
Review
Is It Time for a New Algorithm for the Pharmacotherapy of Steroid-Induced Diabetes?
by Aleksandra Ostrowska-Czyżewska, Wojciech Zgliczyński, Lucyna Bednarek-Papierska and Beata Mrozikiewicz-Rakowska
J. Clin. Med. 2024, 13(19), 5801; https://doi.org/10.3390/jcm13195801 - 28 Sep 2024
Cited by 4 | Viewed by 10074
Abstract
Glucocorticoids (GS) are widely used in multiple medical indications due to their anti-inflammatory, immunosuppressive, and antiproliferative effects. Despite their effectiveness in treating respiratory, skin, joint, renal, and neoplastic diseases, they dysregulate glucose metabolism, leading to steroid-induced diabetes (SID) or a significant increase of [...] Read more.
Glucocorticoids (GS) are widely used in multiple medical indications due to their anti-inflammatory, immunosuppressive, and antiproliferative effects. Despite their effectiveness in treating respiratory, skin, joint, renal, and neoplastic diseases, they dysregulate glucose metabolism, leading to steroid-induced diabetes (SID) or a significant increase of glycemia in people with previously diagnosed diabetes. The risk of adverse event development depends on the prior therapy, the duration of the treatment, the form of the drug, and individual factors, i.e., BMI, genetics, and age. Unfortunately, SID and steroid-induced hyperglycemia (SIH) are often overlooked, because the fasting blood glucose level, which is the most commonly used diagnostic test, is insufficient for excluding both conditions. The appropriate control of post-steroid hyperglycemia remains a major challenge in everyday clinical practice. Recently, the most frequently used antidiabetic strategies have been insulin therapy with isophane insulin or multiple injections in the basal–bolus regimen. Alternatively, in patients with lower glycemia, sulphonylureas or glinides were used. Taking into account the pathogenesis of post-steroid-induced hyperglycemia, the initiation of therapy with glucagon-like peptide 1 (GLP-1) analogs and dipeptidyl peptidase 4 (DPP-4) inhibitors should be considered. In this article, we present a universal practical diagnostic algorithm of SID/SIH in patients requiring steroids, in both acute and chronic conditions, and we present a new pharmacotherapy algorithm taking into account the use of all currently available antidiabetic drugs. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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18 pages, 2199 KB  
Systematic Review
Once-Weekly Insulin Icodec in Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Clinical Trials (ONWARDS Clinical Program)
by Giuseppe Lisco, Anna De Tullio, Vincenzo De Geronimo, Vito Angelo Giagulli, Edoardo Guastamacchia, Giuseppina Piazzolla, Olga Eugenia Disoteo and Vincenzo Triggiani
Biomedicines 2024, 12(8), 1852; https://doi.org/10.3390/biomedicines12081852 - 14 Aug 2024
Cited by 8 | Viewed by 9429
Abstract
Background. One hundred years have passed since the discovery of insulin, which is one of the most relevant events of the 20th century. This period resulted in extraordinary progress in the development of novel molecules to improve glucose control, simplify the insulin regimen, [...] Read more.
Background. One hundred years have passed since the discovery of insulin, which is one of the most relevant events of the 20th century. This period resulted in extraordinary progress in the development of novel molecules to improve glucose control, simplify the insulin regimen, and ameliorate the quality of life. In late March 2024, the first once-weekly basal analog Icodec was approved for diabetes mellitus, generating high expectations. Our aim was to systematically review and meta-analyze the efficacy and safety of Icodec compared to once-daily insulin analogs in type 1 (T1D) and type 2 diabetes (T2D). Methods. PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov were searched for randomized clinical trials (RCTs). Studies were included for the synthesis according to the following prespecified inclusion criteria: uncontrolled T1D or T2D, age ≥ 18 years, insulin Icodec vs. active comparators (Degludec U100, Glargine U100, Glargine U300, and Detemir), phase 3, multicenter, double-blind or open-label RCTs, and a study duration ≥ 24 weeks. Results. The systematic review included 4347 patients with T1D and T2D inadequately controlled (2172 randomized to Icodec vs. 2175 randomized to once-daily basal analogs). Icodec, compared to once-daily basal analogs, slightly reduced the levels of glycated hemoglobin (HbA1c) with an estimated treatment difference (ETD) of −0.14% [95%CI −0.25; −0.03], p = 0.01, and I2 68%. Patients randomized to Icodec compared to those on once-daily basal analogs had a greater probability to achieve HbA1c < 7% without clinically relevant or severe hypoglycemic events in 12 weeks from randomization with an estimated risk ratio (ERR) of 1.17, [95%CI 1.01, 1.36], p = 0.03, and I2 66%. We did not find a difference in fasting glucose levels, time in range, and time above range between Icodec and comparators. Icodec, compared to once-daily basal analogs, resulted in a slight but statistically significant weight gain of 0.62 kg [95%CI 0.25; 0.99], p = 0.001, and I2 25%. The frequency of hypoglycemic events (ERR 1.16 [95%CI 0.95; 1.41]), adverse events (ERR 1.04 [95%CI 1.00; 1.08]), injection-site reactions (ERR 1.08 [95%CI 0.62; 1.90]), and the discontinuation of treatments were similar between the two groups. Icodec was found to work better when used in a basal-only than basal-bolus regimen with an ETD in HbA1c of −0.22%, a probability of achieving glucose control of +33%, a probability of achieving glucose control without clinically relevant or severe hypoglycemia of +28%, more time spent in target (+4.55%) and less time spent in hyperglycemia (−5.14%). The risk of clinically relevant or severe hypoglycemic events was significantly higher when background glinides and sulfonylureas were added to basal analogs (ERR 1.42 [95%CI 1.05; 1.93]). Conclusion. Insulin Icodec is substantially non-inferior to once-daily insulin analogs in T2D, either insulin-naïve or insulin-treated. However, Icodec works slightly better than competitors when used in a basal-only rather than basal-bolus regimen. Weight gain and hypoglycemic risk are substantially low but not negligible. Patients’ education, adequate lifestyle and pharmacological interventions, and appropriate therapy adjustments are essential to minimize risks. This systematic review is registered as PROSPERO CRD42024568680. Full article
(This article belongs to the Special Issue New Advances in Insulin—100 Years since Its Discovery)
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20 pages, 2534 KB  
Article
Testing the Quality of the Mobile Application Interface Using Various Methods—A Case Study of the T1DCoach Application
by Marek Milosz, Małgorzata Plechawska-Wójcik and Mariusz Dzieńkowski
Appl. Sci. 2024, 14(15), 6583; https://doi.org/10.3390/app14156583 - 27 Jul 2024
Cited by 2 | Viewed by 2731
Abstract
The T1DCoach mobile application is designed to educate patients—children with type 1 diabetes (T1D) and their caregivers and diabetes educators. The idea behind the mobile application is that its users perform actions that the patient needs to perform in real life. These include [...] Read more.
The T1DCoach mobile application is designed to educate patients—children with type 1 diabetes (T1D) and their caregivers and diabetes educators. The idea behind the mobile application is that its users perform actions that the patient needs to perform in real life. These include measuring blood glucose levels, operating the insulin pump, meal calculation, bolus administration, etc. These in-application activities are performed on the patient’s digital twin. To increase user engagement, gamification elements have been implemented in the application. An important element of the T1DCoach mobile application is its interface, which should be adapted to very different groups of users: children, their caregivers and educators. In addition to presenting the T1DCoach application, the paper presents the stage examining the quality of the interface using three research groups: children, their caregivers and educators. The research was conducted using the scenario method, using eye-tracking, recording activities and thinking aloud. After the application testing sessions, surveys were carried out using the System Usability Scale method and focus group interviews were conducted. The research results are presented in the article along with the most important recommendations for improving the application interface. Full article
(This article belongs to the Special Issue Application of Information Systems)
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