Search Results (18)

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

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

Multiple daily injections via subcutaneous route are the primary modes of insulin delivery for patients with Diabetes Mellitus. While this process is invasive, painful and may cause patients to develop lipohypertrophy at injection site, the perception of fear surrounding this process causes patients to delay in initiation and remain persistent with insulin therapy over time. Moreover, poor glycemic control may often lead to acute complications, such as severe hypoglycemia and nocturnal hypoglycemia, especially in older patients with diabetes. To address the imperative need for a patient-convenient non-invasive insulin therapy, an insulin-loaded arginine-coated self-emulsifying nanoglobule system (INS-LANano) was developed for nasal delivery of insulin with a biodegradable cationic surfactant—Lauroyl Ethyl Arginate (LAE). Incorporation of LAE resulted in formation of positively charged nanoglobules with L-arginine oriented on the surface. LANano enabled binding of insulin molecules on the surface of nanoglobules via an electrostatic interaction between negatively charged α-helix and LAE molecules at physiological pH. INS-LANano showed a hydrodynamic diameter of 23.38 nm with a surface charge of +0.118 mV. The binding efficiency of insulin on LANano globules was confirmed by zeta potential, circular dichroism (CD) spectroscopy and centrifugal ultrafiltration studies. The attachment of insulin with permeation-enhancing nanoglobules demonstrated significantly higher in vitro permeability of insulin of 15.2% compared to insulin solution across human airway epithelial cell (Calu-3) monolayer. Upon intranasal administration of INS-LANano to diabetic rats at 2 IU/kg insulin dose, a rapid absorption of insulin with significantly higher Cmax of 14.3 mU/L and relative bioavailability (BA) of 23.3% was observed. Therefore, the INS-LANano formulation significant translational potential for intranasal delivery of insulin Full article

Patients with type 2 diabetes (T2D) and end-stage kidney disease (ESKD) on renal replacement therapy represent a specific population with high morbidity and mortality, an increased risk of hypoglycemic episodes and large intra- and interdialysis glycemic variability. Antidiabetic treatment adjustment is therefore challenging, especially in insulin-treated patients. Continuous glucose monitoring (CGM) is increasingly proposed to T2D patients on hemodialysis (HD), although data regarding flash monitoring systems (FMSs) and real-time CGM (rtCGM) in HD patients are limited. Small CGM pilot studies of a short duration demonstrated improvements in glycemic control and decreased hypoglycemic events, despite a lower accuracy of CGM as compared to capillary blood glucose. Moreover, CGM–drug interactions with vitamin C, mannitol and paracetamol can occur in HD diabetic patients and need further study. Despite these shortcomings, professional CGM has the potential to become an integral part of glucose monitoring of HD patients treated with insulin. Personal CGM prescriptions can especially be useful in highly selected, motivated T2D HD patients on multiple daily insulin injections or experiencing frequent hypoglycemia with preserved diabetes self-management abilities or in whom diabetes is fully managed by medical providers. A close collaboration between the clinical staff working on HD units and diabetology teams, and ongoing patient education, are mandatory for optimal use of CGM. Full article

Type 1 diabetes is a chronic illness in which the native beta (β)-cell population responsible for insulin release has been the subject of autoimmune destruction. This condition requires patients to frequently measure their blood glucose concentration and administer multiple daily exogenous insulin injections accordingly. Current treatments fail to effectively treat the disease without significant side effects, and this has led to the exploration of different approaches for its treatment. Gene therapy and the use of viral vectors has been explored extensively and has been successful in treating a range of diseases. The use of viral vectors to deliver β-cell transcription factors has been researched in the context of type 1 diabetes to induce the pancreatic transdifferentiation of cells to replace the β-cell population destroyed in patients. Studies have used various combinations of pancreatic and β-cell transcription factors in order to induce pancreatic transdifferentiation and have achieved varying levels of success. This review will outline why pancreatic transcription factors have been utilised and how their application can allow the development of insulin-producing cells from non β-cells and potentially act as a cure for type 1 diabetes. Full article

The diagnosis of gestational diabetes is usually very stressful for pregnant women, especially because they fear that insulin treatment may become necessary. Knowledge about personal risk factors predicting the probability of insulin treatment could therefore help to improve acceptance of the diagnosis and therapy adherence. The aim of this study was to find potential risk factors for insulin dependency and treatment requirements using information available at the time of diagnosis of gestational diabetes during pregnancy. We included 454 singleton pregnancies diagnosed ≥24 weeks of gestation. Multivariate regression analysis was used to evaluate independent associations of metabolic, anthropometric and fetal ultrasound parameters with the general need for insulin treatment and further stratified treatment options: diet (n = 275), bolus insulin only (n = 45), basal insulin only (n = 73) and multiple daily injections (n = 61). Receiver operator characteristics and cut-off values for independent variables were generated. Treatment groups differed significantly concerning pre-pregnancy weight and BMI as well as fasting glucose and 1 h glucose test values. Significant cut-offs for insulin dependency were HbA1c level of 5.4%, FPG of 5.5 mmol/L and 1 h glucose of 10.6 mmol/L. At time of diagnosis, certain patient characteristics and measurements can help to predict treatment necessities and therefore improve individualized counselling. Full article

Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure for patients with chronic pancreatitis and poor quality of life. Euglycemia is critical for islet cell survival and engraftment. We reviewed clinical care practice and hypothesized that early in-hospital transition from intravenous insulin to insulin pump therapy, managed by an endocrine unit trained on post-surgical care, would improve glucose control and impact the length of hospital stay. We completed a retrospective analysis of 40 pediatric patients who underwent TPIAT. Comparative hospitalized postoperative groups included those who received insulin intravenously, followed by multiple daily injections, subsequently managed by pump therapy (n = 14), versus those who received insulin intravenously followed by early pump therapy provided on the endocrine unit trained to manage post-surgical patients (n = 26). The outcomes analyzed included percentage of blood glucoses in target (4.44–6.66 mmol/L (80–120 mg/dL)), hypoglycemia (<3.33 mmol/L (<60 mg/dL)) and hyperglycemia (>7.77 mmol/L (>140 mg/dL)), blood glucose variability, and length of hospital unit stay post-ICU. Hospitalized patients with early transition to pump therapy on a specialized endocrine unit had a higher proportion of glucose values in the target range (61% vs. 51%, p = 0.0003), a lower proportion of hyperglycemia (15% vs. 19%, p = 0.04), and a lower proportion of hypoglycemia, though not statistically significant (3.4% vs. 4.4%, p = 0.33). Early pump users also had lower variability in glucose values over 10 days post-intravenous insulin (p = 0.001), and the post-transition median length of stay was shorter by 5 days (median: 11.5 vs. 16.5 days, p = 0.005). Early in-hospital pump therapy managed by the specialized endocrine unit improved glucose outcomes and reduced the duration of in-unit stay. Full article

Insulin therapy is frequently required to achieve glycemic targets (A1c) in type 2 diabetes (T2D); however, clinicians and patients face barriers with the complexities of multiple daily injection regimens. Patch-like wearable insulin devices, such as V-Go, may simplify and optimize this complexity. This study evaluated the change in A1C and insulin total daily dose (TDD) in a suboptimally-controlled (not achieving A1C targets) T2D population after switching to V-Go. A retrospective chart analysis at a diabetes clinic was performed to evaluate change in A1c measurements from baseline (V-Go initiation) to end of study observation. Of the 139 patients enrolled, A1C significantly decreased from baseline (−1.5 ± 1.79%; p < 0.001). Patients prescribed insulin at baseline (n = 122) used significantly less insulin TDD (−8 u/day; p = 0.006). The percentage of patients meeting the target of A1C < 8% increased from 14% at baseline to 48% at study completion (p = 0.008). Patients prescribed a basal-bolus regimen prior to V-Go achieved an A1C reduction of 1.5 ± 2.0% (p < 0.0001) and experienced the greatest reduction in TDD (−24 u/day; p < 0.0001). Thus, patients switching to V-Go from a variety of therapies at baseline experienced reductions in A1C while using less insulin, with a reduction in clinically relevant hypoglycemia, indicating the potential benefit of V-Go in optimizing and simplifying T2D care. Full article

Type 1 diabetes (T1D) is an autoimmune condition where the body’s immune cells destroy their insulin-producing pancreatic beta cells leading to dysregulated glycaemia. Individuals with T1D control their blood glucose through exogenous insulin replacement therapy, often using multiple daily injections or pumps. However, failure to accurately mimic intrinsic glucose regulation results in glucose fluctuations and long-term complications impacting key organs such as the heart, kidneys, and/or the eyes. It is well established that genetic and environmental factors contribute to the initiation and progression of T1D, but recent studies show that epigenetic modifications are also important. Here, we discuss key epigenetic modifications associated with T1D pathogenesis and discuss how recent research is finding ways to harness epigenetic mechanisms to prevent, reverse, or manage T1D. Full article