Insulin Delivery Research Articles

Development of a pH-Sensitive Nanoparticle via Self-Assembly of Fucoidan and Protamine for the Oral Delivery of Insulin.

Objectives: Oral insulin delivery has received much attention over the past 20 years due to its high compliance. The aim of this study is to prepare nanoparticles for the oral delivery of insulin; Methods: Fucoidan and protamine were used to prepare a pH-sensitive nanoparticle via self-assembly. The secondary structure and in vitro stability of the nanoparticles were characterized using FTIR, XRD, ITC, and TEM. the nanoparticles had a controlled release effect on insulin in simulated intestinal fluid. The pre-liminary therapeutic effect on high-fat-fed type 2 diabetic mice; Results: When the fucoidan/protamine mass ratio was 10:3 (w/w), the particle size and zeta potential were 140.83 ± 1.64 nm and -48.13 ± 0.61 mV.The encapsulation efficiency of insulin was 62.97 ± 0.59%. The preliminary therapeutic effect on type 2 diabetic mice showed that the fasting blood glucose of diabetic mice decreased from 10.28 ± 0.88 mmol/L to 9.22 ± 0.64 mmol/L, the area under the curve value of oral glucose tolerance test was reduced by 11.70%, and the insulin se-cretion of diabetic mice was increased by 13.3%; Conclusions: The nanoparticles were prepared successfully by self-assembly. The empty and insulin-loaded nanoparticles remained stable in simulated gastric fluid, and the nanoparticles had a controlled release effect on insulin in simulated intestinal fluid. Moreover, insulin-loaded nanoparticles could relieve on type 2 diabetic mice.

Insulin-Loaded Graphene Oxide Microparticles: Synthesis, Characterization, Insulin Delivery, and Physical Interactions Analysis

Insulin-Loaded Graphene Oxide Microparticles: Synthesis, Characterization, Insulin Delivery, and Physical Interactions Analysis

Glycaemic outcomes in adults with type 2 diabetes over 34 weeks with the Omnipod® 5 automated insulin delivery system.

The aim was to evaluate the effect of extended use of the Omnipod® 5 automated insulin delivery (AID) system in adults with type 2 diabetes and suboptimal glycaemic control. Following an 8-week single-arm, multicentre, outpatient trial of AID in adults with type 2 diabetes and baseline ≥ 64 mmol/mol, participants were given the opportunity to continue use of the AID system in a 26-week (~6 month) extension phase. The primary safety endpoints were percentage of time with sensor glucose ≥ 250 mg/dL and < 54 mg/dL. Additional glycaemic measures, including percentage of time in range (TIR) (70-180 mg/dL) and HbA1c, were evaluated. The use of non-insulin anti-hyperglycaemic medications was permitted throughout the entire study. During the initial 8-week study, participants (N = 22) achieved a decrease in percentage of time ≥ 250 mg/dL from 27.4% ± 21.0% to 10.5% ± 8.8% (p < 0.0001), which further decreased to 9.7% ± 9.2% during the extension phase (p = 0.0002 vs. standard therapy). Percentage of time < 54 mg/dL remained low from standard therapy through extension (median [interquartile range] 0.00% [0.00%, 0.06%] vs. 0.02% [0.00%, 0.05%], p > 0.05). HbA1c decreased by 1.6% ± 1.2% (15.5 ± 13.1 mmol/mol, p < 0.0001) and TIR increased by 22.4% ± 19.2% (p < 0.0001) from standard therapy through extension with no significant change in body mass index and without an observed increase in total daily insulin requirements. These longer-term findings of Omnipod 5 AID system use demonstrate the potential value of AID in helping people with type 2 diabetes reach glycaemic targets.

Experiences of adolescents and young adults with type 1 diabetes and chronically elevated glucose levels following the transition from multiple daily injections to advanced hybrid closed-loop: A qualitative study.

To understand experiences of using second-generation advanced hybrid closed-loop (AHCL) therapy in adolescents and young adults with chronically elevated glucose levels who were previously using multiple daily injections (MDI) therapy. Semi-structured interviews with participants aged 13-25 years, on AHCL therapy for 3 months as part of a single-arm prospective study. Key inclusions: HbA1c ≥69 mmol/mol (8.5%); diabetes duration ≥1 year; and using MDI therapy prior to the study. Qualitative content analysis was used to identify themes and subthemes. Interviews were conducted among 14 participants with mean age 19.4 ± 4.3 years and mean baseline HbA1c 90 ± 25 mmol/mol (10.4 ± 4.5%). Three themes were identified: (1) substantially improved glucose levels improved perceptions of overall health; (2) features of AHCL aid in adoption and ongoing self-management; and (3) burden of care was reduced through automation of insulin delivery. Overall, there were positive impacts on physical, mental and social well-being. Participants were willing to overlook minor frustrations with AHCL because of the vast benefits that they had experienced. Four participants reported transient pseudo-hypoglycaemia: symptoms of hypoglycaemia when objectively measured glucose was in the clinically recommended range (3.9-10 mmol/L, 70-180 mg/dL). Transition to AHCL therapy positively impacted diabetes management in adolescents and youth with chronically elevated glucose levels. It appears to create a window of opportunity in which youth may re-engage with diabetes management. Pseudo-hypoglycaemia can occur during the transition to AHCL. This could be a barrier to AHCL uptake and is likely to require individualised support.

Experiences of People With Type 1 Diabetes Using the iLet Bionic Pancreas in Primary Care: A Qualitative Analysis

This qualitative substudy sought to identify and understand the experiences of primary care patients with type 1 diabetes using the iLet Bionic Pancreas (Beta Bionics, Inc.) during the first clinical trial testing the automated insulin delivery (AID) system in the primary care setting. Participants in that clinical trial completed a brief semi-structured interview after the trial’s completion during which they were asked questions related to their perceptions of and experiences with using the iLet AID system. Analysis of 16 interviews revealed five major themes, which highlighted the positive and beneficial impact of the system on psychological and behavioral aspects of diabetes management.

8475 Automated Insulin Delivery System with Concentrated Regular U500 Insulin in Cushing Syndrome

Abstract Disclosure: F. Erenler: None. J. Aurora: None. Background: Concentrated regular U-500 (U-500R) insulin is commonly used in patients with T2DM, who are highly insulin-resistant, requiring more than 200 units of insulin per day. Utilizing U-500R reduces the number of daily injections, decreases injection volume, and improves cost effectiveness. There has been a case report with U-500R in an automated insulin delivery (AID) system with successful results (1). To our knowledge there is no data on AID system use in Cushing patients with T2DM using U-500R. We present a case of a patient with Cushing Syndrome (CS) with poor BG control using &amp;gt;250 units/day of SC U-500R with improved BG control after switching to Omnipod 5 AID system. Clinical Case: A 57 y.o. male initially presented with hypogonadotropic hypogonadism and subsequently diagnosed with ACTH-dependent CS, which is complicated by obesity, uncontrolled T2DM, lower extremity wounds, and DVTs. He was diagnosed with CS with multiple abnormal 1 mg dexamethasone suppression tests (DST) (max AM cortisol 5.9 mcg/dL; RR &amp;lt;1.8 mcg/dL, dexamethasone level 300), elevated urine free cortisol (UFC) (max UFC/Cr 77.6 mcg/mg/L; RR: 5-64 mcg/24-hr) and elevated salivary cortisol (max cortisol 0.2 mcg/dL; RR: &amp;lt;0.09 mcg/dL). He had suppressed cortisol with 8 mg DST. An MRI sella showed left-sided hypoechoic 0.9 cm mass. Desmopressin (DDAVP) stimulation test and Ga-68 DOTATATE-PET scan were negative. As a result of his abnormal MRI sella and elevated cortisol, he underwent transsphenoidal surgery of the left pituitary. Pathology was non-diagnostic for a pituitary adenoma. Post-op 24-hr UFC and 1 mg DST levels remained high. DDAVP stimulation test and Ga-68 DOTATATE-PET were repeated post-op and were negative. Due to complications of CS, he was initially treated with cabergoline, but switched to osilodrostat due to intolerances. He is currently on 2 mg BID dose and 24-hr UFC has been normal since then (UFC 20 mcg/L, Cr 0.67 mg, UFC/Cr 12 mcg/mg/L). He continued to have uncontrolled hyperglycemia despite normalization of UFC. On his CGM data, he was in target range (70-180 mg/dL) 5% of the time despite using U-500R 95 units SC TID. Given his severe hyperglycemia and insulin resistance, he was switched to an AID system with U-500R and his time in target range improved over 60% after a month of use and his total daily dose of insulin decreased to less than 200 units. Conclusion: U-500R proved to be safe and effective with Omnipod 5 AID. To our knowledge, this is the first reported patient with CS using U-500R with Omnipod 5 AID. In patients without CS, the AID algorithm continuously kept BG well below the set target, especially overnight. Notably, our patient did not have this overnight hypoglycemia trend, which should be expected with his disease. We are hoping to increase the awareness of U-500R with AID systems, especially for patients with incurable CS. Reference:1.Aurora J Jr, Saraswat A. J Endocr Soc. 2023;7(Suppl 1):bvad114.873. Presentation: 6/3/2024

7431 Non-Insulin Treatment of Type 1 Diabetes Mellitus: The Power of GLP-1 and GLP-1/GIP RA

Abstract Disclosure: J. Ferri-Guerra: None. E. Kasper-Guerra: None. O. Abdulhussein: None. G. Madrigal Loria: None. J. Ambalavanan: None. K. Zhou: None. Background: Insulin is the mainstay of treatment of patients with type 1 diabetes mellitus (T1D). However, patients with T1D can also potentially benefit from adjunctive therapies such as GLP-1 receptor agonists or GLP-1/GIP receptor agonists, especially when obesity and elevated cardiovascular risk are present. Case 1: A 64-year-old male with severe coronary artery disease requiring revascularization and obesity with T1D has been wearing a pump for insulin delivery since the age of 43, started on closed loop system Control IQ with Tandem in April 2022. In December 2022, patient had myocardial infarction. At that time, Hba1c was elevated at 7.6% and BMI was elevated at 32.5 kg/m2, and patient was considered a good candidate for tirzepatide, which was prescribed. The tirzepatide dose was slowly increased, up to 10 mg weekly. The new therapy resulted in loss of 17 kg (20.1% decrease of body weight) with only some mild nausea. There was an improvement in HbA1c to 7.1% and a dramatic reduction in daily average insulin use from 90 units to 52 units. Case 2: A 59-year-old female with obesity and T1D diagnosed at the age of 8 had been wearing insulin pump, Medtronic 670G in manual mode, for insulin delivery for the past few years with poor glycemic control. In August 2021, patient was prescribed semaglutide for post prandial hyperglycemia and obesity management (BMI at 31.6kg/m2). Since being on the medication, she lost 12kg (16.8% decrease in body weight), despite being on the lowest dose of 0.25 mg (maximum tolerated). Her HbA1c has improved from 8.2% when therapy was initiated, to 7% with just the introduction of semaglutide to her insulin regimen. Conclusion: Although insulin is a required therapy for patients with T1D, adjunctive therapies may improve glycemic control, reduce insulin requirements and promote weight loss. GLP-1 and dual GLP-1/GIP receptor agonists should be considered for these patients. Presentation: 6/1/2024

Advances in diabetes technology within the digital diabetes ecosystem.

Ongoing innovations in glucose monitoring, insulin delivery, and telehealth technologies have created a digital diabetes ecosystem populated by connected tools and technologies that have been shown to improve clinical outcomes, lower costs, and reduce the burden of diabetes. Advances in connected continuous glucose monitoring devices, insulin pumps, and insulin pens have led to the development of automated insulin delivery systems that modulate insulin infusion based on sensor glucose data. Similar integrations of continuous glucose monitoring and connected blood glucose meter data into "smart" pens have lessened the guesswork of intensive insulin management for individuals who prefer traditional injection therapy. A growing number of health apps that can be accessed through smartphones and wearable devices provide information and advice that support individuals in adopting healthier lifestyles. The differences in features and functionality give users the ability to select the devices that best meet their unique requirements and preferences. This article reviews the most current digital diabetes technologies and discusses how the connectivity of these tools can create an overarching architecture of feedback mechanisms that monitor an individual's health status, motivate and enhance adherence to self-management, and provide advice and decision-support tools to clinicians as well as other members of the health care team to make living with diabetes more manageable.

Intelligent microneedle patch based on functionalized alginate and chitosan for long-term self-regulated insulin delivery

Severely diabetic patients need insulin input to maintain the body's glycemic balance. However, traditional injection methods are often associated with poor adherence and an increased risk of hypoglycemia. Microneedle technology offers a promising solution by minimizing pain and trauma during insulin administration. Nonetheless, achieving prolonged glycemic control by microneedle with high insulin loading remains a significant challenge. Herein, we introduce an innovative microneedle patch that draws inspiration from the elegant light-induced blooming of water lily petals. The patch features a glucose-responsive hydrogel network crafted from two modified polysaccharide polymers, which enables the delivery of long-acting insulin without depending on glucose oxidase. By incorporating phenylboronic acid-modified sodium alginate, quaternary ammonium chitosan, and polyvinyl alcohol into a hydrogel matrix, we have created a microneedle system that harbors dynamic borate ester linkages and electrostatic attractions, resulting in heightened sensitivity to blood glucose levels. The electrostatic interaction acts as a relatively stable crosslinking point, balancing the dynamic reproducibility response based on the borate ester bond. This self-adaptive hydrogel can regulate insulin-controlled release by responding to changes in glucose concentration. Herein, we achieved massive insulin loading (20 IU) with long lasting glycaemic control (48 h) in a single treatment of diabetic SD rats.

Injectable Gelled Multiple Emulsion for Glucose-Responsive Insulin Delivery.

A glucose-responsive insulin delivery system that sustains blood glucose equilibrium for an extended duration can address the low therapeutic window of insulin in diabetes treatment. Herein, insulin is loaded in a water-in-oil-in-water (W1/O/W2) gelled multiple emulsion using poly (4-vinylphenylboronic acid) (PVPBA) homopolymer as an effective emulsifier. The gelled multiple emulsion exhibits a high encapsulation efficiency (99%), enhanced stability and remarkable shear-thinning behavior, making it easy to inject. Under hyperglycemic conditions, the gelled emulsion system instantly binds to glucose molecules and reduces the hydrogen bonds of the PVPBA homopolymer, resulting in insulin release. In a streptozotocin-induced type 1 diabetic mouse model, a single subcutaneous injection of the gelled emulsion rapidly responds to high blood glucose concentration (BGC)and release insulin in a glucose dependent manner, thus prolonging the antihyperglycemic effect compared with free insulin.

Evaluation of a mucoadhesive auto-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration

This study investigated the potential of self-nanoemulsifying drug delivery systems (SNEDDS) to optimize the oral bioavailability of insulin. Insulin complexes with phospholipids and enzymatically-modified phospholipids were developed and incorporated into the SNEDDS using Lauroglycol FCC as the oily phase and Cremophor EL and Labrafil M1944CS as the surfactant and co-surfactant, respectively. Additionally, mucoadhesive polysaccharides (sodium alginate and guar gum) were added further to enhance the bioavailability of insulin in these systems. The objective was to increase the bioavailability and bioactivity of an insulin-modified phosphatidylcholine complex by incorporating mucoadhesives into the SNEDDS. After polymer inclusion, the resulting nanoemulsions exhibited droplet diameters ranging from 57 to 83 nm. Cytotoxicity and apparent permeability tests were conducted on Caco-2 and NIH 3 T3 cell lines, revealing that toxicity was related to the concentrations of insulin and surfactant in the nanosystems—formulations containing guar gum as a mucoadhesive showed better tolerance to cell death in the Caco-2 line. In a murine diabetes model, the SNEDDS were observed to reduce glucose levels by up to 61.63 %, with a relative bioavailability of 2.25 % compared to subcutaneously administered insulin. These results suggest that SNEDDS incorporating mucoadhesives could represent a promising strategy for improving oral insulin delivery.

TNF-α inhibitors for type 1 diabetes: exploring the path to a pivotal clinical trial.

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β-cells in the pancreas. This destruction leads to chronic hyperglycemia, necessitating lifelong insulin therapy to manage blood glucose levels. Typically diagnosed in children and young adults, T1D can, however, occur at any age. Ongoing research aims to uncover the precise mechanisms underlying T1D and to develop potential interventions. These include efforts to modulate the immune system, regenerate β-cells, and create advanced insulin delivery systems. Emerging therapies, such as closed-loop insulin pumps, stem cell-derived β-cell replacement and disease-modifying therapies (DMTs), offer hope for improving the quality of life for individuals with T1D and potentially moving towards a cure. Currently, there are no disease-modifying therapies approved for stage 3 T1D. Preserving β-cell function in stage 3 T1D is associated with better clinical outcomes, including lower HbA1c and decreased risk of hypoglycemia, neuropathy, and retinopathy. Tumor Necrosis Factor alpha (TNF-α) inhibitors have demonstrated efficacy at preserving β-cell function by measurement of C-peptide in two clinical trials in people with stage 3 T1D. However, TNF-α inhibitors have yet to be evaluated in a pivotal trial for T1D. To address the promising clinical findings of TNF-α inhibitors in T1D, Breakthrough T1D convened a panel of key opinion leaders (KOLs) in the field. The workshop aimed to outline an optimal clinical path for moving TNF-α inhibitors to a pivotal clinical trial in T1D. Here, we summarize the evidence for the beneficial use of TNF-α inhibitors in T1D and considerations for strategies collectively identified to advance TNF-α inhibitors beyond phase 2 clinical studies for stage 3 T1D.

Colonic targeting insulin-loaded trimethyl chitosan nanoparticles coated pectin for oral delivery: In vitro and In vivo studies

Colon-targeted delivery offers several benefits for oral protein delivery, such as low proteolytic enzyme activity, natural pH, and extended residence time, which improve the bioavailability of the encapsulated protein. Therefore, we hypothesize that developing a novel colonic nanocarrier system based on modified chitosan, which enhances solubility at natural pH and is coated with a colon-degradable polymer, will provide an effective delivery system for oral insulin. This study aims to synthesize insulin-loaded pectin-trimethyl chitosan nanoparticles (Ins-P-TMC-NPs) as an oral insulin delivery system and evaluate their efficacy both in vitro and in streptozotocin-induced diabetic male rats. N-trimethyl chitosan (TMC), synthesized via a methylation method, was used to prepare insulin-TMC nanoparticles coated with pectin via the ionic gelation method. The nanoparticles were characterized for their physicochemical properties, cumulative release profile, and surface morphology. In vitro biological cytotoxicity and cellular uptake of the nanoparticles were evaluated against HT-29 cells using an MTT assay and fluorescent microscopy, respectively. The in vivo blood glucose-lowering effect was assessed in diabetic male Sprague–Dawley rats, with in vivo toxicity evaluated in the liver, spleen, duodenum, pancreas, and kidney through histological studies (H&E staining). The results showed that Ins-P-TMC-NPs were spherical, with an average size of 379.40 ± 40.26 nm, a polydispersity index of 24.10 ± 1.03 %, a zeta potential of +17.20 ± 0.52 mV, and a loading efficiency of 83.21 ± 1.23 %. Compared to uncoated TMC nanoparticles, Ins-P-TMC-NPs reduced insulin loss in simulated gastrointestinal fluid by approximately 67.23 ± 0.97 % and provided controlled insulin release in simulated colonic fluid. In vitro bioactivity studies revealed that Ins-P-TMC-NPs were non-toxic, with cell viability of 91.12 ± 0.91 %, and exhibited high cellular uptake in the HT-29 cell line with a fluorescence intensity of 37.80 ± 2.40. Furthermore, in vivo studies demonstrated a sustained reduction in blood glucose levels after oral administration, peaking after 8 h with a glucose reduction of 87 ± 1.03 %. Histological sections showed no signs of toxicity. Overall, the developed colon-targeted oral insulin delivery system shows great potential as a candidate for oral insulin administration.

Oral insulin delivery system development by bioinformatics and protein engineering

Oral insulin delivery system development by bioinformatics and protein engineering

Clinical perspective on innovative insulin delivery technologies in diabetes management.

The primary objective of this study is to report the results of an online questionnaire and the in-person discussion sessions of physicians specializing in diabetes care in which their opinions about current diabetes management was obtained. The Diabetes Innovation Summit 2023 drew attendance from a diverse group of specialized physicians from multiple countries. A comprehensive literature review was conducted to examine the technologies and medical needs associated with diabetes management. Using the results of the review, a questionnaire was developed by three experts from the steering committee to solicit feedback from specialized physicians. The online survey was made accessible between 10th December 2022 and 10th January 2023. Following the online survey, six structured in-person discussion sessions were conducted with specialized physicians from the Middle East, Central-Eastern Europe, and North Africa regions. The study revealed that about 59% of survey requests were answered, with many participants being pediatric endocrinologists from North Africa. Around 60% of diabetes patients followed Multiple Daily Injections (MDI) according to specialized physicians. Among MDI users, 62% employed Blood Glucose Monitors (BGM), 31% used intermittent-scanning Continuous Glucose Monitors (isCGM), and 23% used CGM. In North Africa, nearly 90% of patients used MDI due to financial constraints. While physicians focused on both Time in Range (TIR) and HbA1c for MDI-treated patients, satisfaction with TIR achieved was expressed by 31%, while 74·1% believed Real-Time CGM (rtCGM) was effective. Concerns arose about potentially misleading HbA1c results and the relatively low patient achievement of target TIR despite CGM usage. The Smart MDI System was seen favorably compared to other applications. The system's affordability was a significant barrier, particularly in the Middle East and Africa. The present study highlights that physicians are generally supportive of utilizing new technology. The questionnaires and the open discussion revealed the expectation that the Smart MDI technology provides better control, primarily by identifying missed boluses, while expressing concerns on the use of the technology by teenagers and children, who might forget the device and be reluctant to use in public, and by the older population, who might be challenged by the technology.

Tecnología aplicada a la diabetes

Diabetes technology refers to devices and applications that people with diabetes use to help manage their disease. There are two main categories: blood glucose monitoring systems (including continuous glucose monitoring (CGM) systems) and insulin delivery devices (including insulin pumps and smart insulin pens). CGM devices measure interstitial blood glucose continuously or intermittently (flash measurements), showing alerts and trends that help predict glucose behavior. The data are represented by the ambulatory glucose profile, which provides measurements and a summary graph to aid in its interpretation. Insulin pumps or continuous subcutaneous insulin infusion systems are devices that infuse rapid-acting insulin continuously with the objective of maintaining glucose levels in range. Among these, hybrid closed loop systems are capable of adjusting insulin infusion according to CGM blood glucose figures. Smart insulin pens are linked to smartphone apps and have features that help patients manage their diabetes (dose reminder, bolus calculator, active insulin monitoring).

Real-world efficacy and safety of open-source automated insulin delivery for people with type 1 diabetes mellitus: Experience from mainland China

BackgroundOpen-source automated insulin delivery systems are increasingly adopted yet predominantly discussed outside of Asia. This study aimed to describe efficacy and safety of android artificial pancreas (AAPS) in people with type 1 diabetes mellitus (T1DM) from mainland China. MethodsThis real-world study recruited people who initiated AAPS for ≥ 3 months between 2019 and 2024. Key outcomes included glycated hemoglobin A1c (HbA1c) and metrics from continuous glucose monitoring, rates of diabetic ketoacidosis (DKA) and severe hypoglycemia. Findings292 (male, 46·9 %) participants aged 25·7 (14·7, 35·0) years were included, with 183 (62·7 %) and 68 (23·3 %) using AAPS for 6 and 12 months. Prior-AAPS HbA1c was 7·6 ± 1·7 % with 44·5 % achieving < 7·0 %. After 3 months, mean HbA1c improved by −1·5 ± 2·0 % to 6·3 ± 0·8 % (P < 0.01), with 82·9 % achieving < 7.0 %. Time in range 3·9-10·0 mmol/L (TIR) improved to 78·8 ± 12·9 %, with 80·5 % achieving > 70 %, followed by time below 3·9 mmol/L of 3·9 (2·1, 6·1) %. After 12 months, HbA1c and TIR remained similar at 6·4 ± 1·0 % and 77·9 ± 12·2 %. No DKA and severe hypoglycemia was observed. InterpretationReal-world data from mainland China highlights current uptake of open-source AAPS with potential glycemic benefits. No safety signals are seen. More support to enhance access and utilization of all AID systems in this region is warranted.

Time in range and mean glucose cut-off points for reduction of fetal outcomes in pregnant women with type 1 diabetes using automated insulin delivery systems

AimIn pregnant women with Type 1 Diabetes (T1D), achieving a lower recommended time in range (TIRp,63–140 mg/dl) could have an impact on fetal outcomes. To determine the TIRp and mean glucose cut-off point associated with better fetal outcomes in pregnant women using automated insulin delivery (AID) systems. MethodsA prospective cohort of pregnant women with T1D, using AID systems and followed-up in Latin America was analyzed. Optimal TIRp and mean glucose cut-off points for predicting large for gestational age (LGA) were determined using the Liu method. Fetal outcomes were evaluated for the identified cut-off point and the one recommended by guidelines (TIRp > 70 %). ResultsSixty-two patients were included (mean age 31.9 ± 5.9 years, HbA1c 7.57 %±1.29 %, TIRp 59.8 %±14.6 %). 27.5 % on advanced hybrid closed loop systems (AHCL). LGA (50 vs 17.9 %,p = 0.010) and hyperbilirubinemia (45 % vs 11.8 %,p = 0.016) were more common in patients with TIRp < 59.1 %. Optimal cut-off of TIRp in the second trimester for predicting LGA was < 59.1 % (sensitivity 75 %, specificity 61 %) with an AUC of 0.68(CI 0.48–0.88). Optimal cut-off for mean glucose was 133 mg/dL (sensitivity 69 %, specificity 70 %) with an AUC of 0.70(CI 0.51–0.88) in the same trimester. Better metabolic control during the third trimester was seen in the AHCL users compared to other devices. ConclusionsTIRp > 59.1 % and mean glucose < 133 mg/dl in the second trimester, is associated with lower fetal outcomes of large for gestational age. One of the strategies that would improve TIRp is the early use of AHCL systems. Further studies are needed before a strong recommendation can be made.

Microcrystalline cellulose and itaconic acid pH sensitive semi interpenetrating network hydrogel for oral insulin delivery

Diabetes mellitus is one of the important causes of death worldwide. Generally, a subcutaneous route is used for insulin administration, but has showed low patient compliance. Extensive research has been conducted to identify molecules capable of delivering insulin orally, for this hydrogel based on microcrystalline cellulose and itaconic acid have been produced and explored. Free radical polymerization as a technique was employed for manufacturing the hydrogels using potassium persulphate as initiator and N, N′-methylene bisacrylamide (NNMBA) as a crosslinker. These pH- sensitive exhibited a swelling capacity of up to 20.38 g/g in distilled water and also revealed stronger swelling in glucose solutions than saline solutions. The pH sensitivity of the hydrogels was confirmed by studying the swelling in different pH solutions. Alkaline solutions showed higher swelling than acidic solutions. SEM established the porous nature, and the structure was examined by FTIR analysis. Thermal degradation was examined using TGA. In vitro release study was done by Bradford assay at 595 nm. The result was further confirmed by in-vivo investigations on male Wistar adult rats and hence is an excellent vehicle for oral insulin administration.

Pioneering Oral Insulin Formulations and Delivery Techniques: A Review

The development of oral insulin presents significant promise for diabetes treatment, mitigating peripheral hyperinsulinemia, weight gain, and hypoglycemia while enhancing patient convenience and facilitating rapid insulinization of the liver. Effective oral insulin products are crucial for early intensive insulin therapy, which ensures tight glycaemic control and delays diabetes complications. However, despite the need, oral insulin has faced many challenges, and past technologies have had limited success. Repeated insulin injections can result in local hypertrophy over time generating attention to user-friendly oral insulin delivery systems that are not invasive to the body and copy the natural pathway. This review article examines New methods for oral insulin delivery that have shown promise, using techniques like complexation, hydrogels, and nanoparticles to boost effectiveness, though they still trail injectable insulin. Further studies will help determine how well oral insulin works at various doses and inform the development of competing formulations.