Subcutaneous Insulin Research Articles

FRI654 Concentrated Regular U-500 Insulin In An Automated Insulin Delivery System: A Case Report

Abstract Disclosure: J. Aurora: None. A. Saraswat: 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 have been clinical trials using U-500R for continuous subcutaneous insulin infusion (CSII), particularly in Omnipod which has been shown to improve glycemic control and patient satisfaction without an increase in hypoglycemia (1). In addition, U-500R administration via multiple daily injections (MDI) and an investigational U-500R CSII, have been compared and demonstrated improved glycemic control with both modalities, but an increase in nocturnal hypoglycemia with CSII (2). Automated insulin delivery (AID) systems, or hybrid closed loop systems, have not formally been studied in patients with T2DM using U-500R. We present a case of a patient with T2DM with high insulin resistance using U-500R with Omnipod 5 AID system. Clinical Case: A 54-year-old female with T2DM with high insulin resistance was initially on Omnipod Dash with U-100 insulin lispro with baseline A1c 12.1%. She was transitioned to Omnipod 5 in 2022, and over 4 months A1c improved to 8.8%, GMI 8.8%, TIR 38%, TAR 62%, TBR 0%, CV 35.9%, and automated mode 97%. However, her total daily dose was 134 units leading to pod changes every 1.5 days. She expressed interest in switching to U-500R to reduce pod changes while utilizing her current CSII technology. We switched to U-500R, continued automated mode, increased her 24-hour BG target from 120 mg/dL to 130 mg/dL to reduce hypoglycemia risk, and increased her active insulin time from 3 to 6 hours to reflect U-500R kinetics. After 4 weeks, her GMI improved to 8.0%, TIR 47%, TAR 52%, TBR 1%, CV 45.9%, and automated mode 94%. Although nocturnal BG readings were normal, ranging from 70-130 mg/dL, she was having nightly symptoms of relative hypoglycemia. We then adjusted her BG target overnight to 150 mg/dL, which kept BG between 80-130 mg/dL with resolution of her symptoms. Conclusion: U-500R proved to be safe and effective with Omnipod 5 AID. Despite setting a higher BG target, the algorithm continuously kept BG well below this, particularly overnight. However, the safety mechanisms incorporated with the CSII suspended insulin delivery for predicted hypoglycemia. Further research will be required to adapt the automated dosing algorithm to U-500R to reduce the risk of nocturnal hypoglycemia.

THU293 Enhancement Of Best Practices In Diabetic Ketoacidosis Management Using Standardized Order-sets vs Individual Practitioner Orders

Abstract Disclosure: C. Yim: None. Q. Li: None. T.G. Arnason: None. Diabetic ketoacidosis (DKA) is a hyperglycemic emergency occurring in diabetics due to insulin deficiency. This results in urinary losses of water and electrolytes (sodium, potassium, chloride) and ultimately extracellular fluid volume depletion. Hallmark features of DKA include ketoacidosis, arterial pH < 7.3, bicarbonate <15 mmol/L and an anion gap of >12 mmol/L. The 2018 Diabetes Canada (DC) guidelines outline the key steps of DKA management including fluid resuscitation, resolution of ketoacidosis, correction of electrolytes and management of precipitating factors. Its detailed algorithm identifies three pillars to DKA treatment: IV fluids, serum potassium and acidosis. A 2016 DKA outcome audit at the Royal University Hospital (RUH) in Saskatoon identified that practitioners diverged considerably from (2013) Canadian Diabetes Association guidelines. Subsequently, two standardized preprinted DKA order sets were developed incorporating the 2018 DC recommendations for i) INITIAL and ii) MAINTENANCE DKA management. Their rollout overlapped with annual academic half day sessions on DKA management for postgraduate year 1 residents in internal medicine. These order-sets were initially implemented at RUH in November 2018 and subsequently adopted by some practitioners at St. Paul’s Hospital (SPH). To ensure the order-sets were promoting improved outcomes and adhering to best practices, a retrospective chart review was conducted of all adult DKA admissions at RUH and SPH from Nov. 13, 2018 to December 31, 2020. In total, 279 hospital admissions were reviewed: 99 used practitioners’ own orders, 115 used both initial and maintenance order-sets, 26 used only the initial order-set and 38 used only the maintenance order-set. Use of the INITIAL order set significantly improved compliance (p < 0.0001) with DC 2018 guidelines for recommended insulin dose and timing, fluid resuscitation as well as potassium, sodium and dextrose replacement. Use of the MAINTENANCE order set consistently enhanced outcomes for intravenous fluid selection, subcutaneous insulin overlap, and ensuring a closed anion gap at transition (p < 0.0001). Additionally, the chart review revealed that there were hospital differences for uptake of order sets and compliance to DC 2018 guidelines. There was a significant uptake of order sets at RUH versus SPH (p < 0.0001). RUH consistently met outcomes for appropriate insulin dosing, potassium and dextrose replacement (p < 0.0001). RUH also consistently overlapped IV and SC insulin and ensured a closed insulin gap. The anion gap remained consistently closed post-transition at RUH versus SPH (p = 0.035). These results suggest that utilization of a DKA order set does significantly promote adherence to key best practices outlined in the DC 2018 guidelines. Presentation: Thursday, June 15, 2023

THU374 Fulminant Type 1 Diabetes Mellitus And DKA Secondary To Pembrolizumab

Abstract Disclosure: I. Iqbal: None. M. Khan: None. M. Ahmad: None. R. Mehreen: None. Introduction: Pembrolizumab is a programmed cell death receptor (PD-1) binder on T cells, which promotes their activation against cancer cells. It can also cause unwanted T cell activation against the body’s own cells, leading to type 1 diabetes mellitus (DM1), among other autoimmune phenomena. We are reporting a case of a new onset pembrolizumab-induced fulminant DM1 who presented with diabetic ketoacidosis (DKA). Despite the emerging data on immune checkpoint inhibitors (ICPI), fulminant DM1 with DKA in a previously nondiabetic patient is still uncommon. Case Presentation: A 66-year-old female with a history of recurrent metastatic non-small cell lung cancer (NSCLC) presented to the emergency room (ER) with an extensive itchy rash. She was enrolled in a clinical trial for NSCLC, where she received immunotherapy with pembrolizumab for five months. Rash was treated outpatient for scabies, with no improvement. She was then started on prednisone 40mg daily and betamethasone 0.05% cream. She applied the cream daily but took prednisone orally for only one day, after which she could not tolerate it due to anxiety and restlessness. She ran out of betamethasone three days before coming to ER. On admission, vitals were: Heart rate 90 beats per minute, blood pressure 119/95 mmHg, respirations 20/minute. The exam showed flushed cheeks, red and dry macules on the skin with excoriations, and dry mucus membranes. Random blood glucose levels (BSL) were 660mg/dl. Labs were; HCO3 16mmol/L, Beta-hydroxy butyrate 20mmol/L, anion gap 17mmol/L, Hemoglobin A1c: 5.6%. For DKA, we started an insulin drip. Workup revealed very low C-peptide levels of 0.2ng/ml, with a concomitant BSL of 500mg/dL. Anti-islet cell and anti-glutamic acid decarboxylase antibodies (anti-GAD) were positive with levels of 0.04 nmol/L and 0.07 nmol/L, respectively. Once she stabilized and the anion gap closed, she was transitioned to subcutaneous insulin and discharged on 42 units of Lantus, along with 12 units of premeal Lispro and sliding-scale insulin. She was removed from the clinical trial due to complications. Unfortunately, she got readmitted with influenza A, Staphylococcus aureus bacteremia, and another episode of DKA, complicated with respiratory failure, and she decided on hospice. The patient passed away after two days. Conclusion: Immune-related adverse event of new-onset fulminant DM1, leading to DKA, is a serious and potentially fatal complication of pembrolizumab. For patients receiving pembrolizumab, who have uncontrolled BSL, we suggest checking the anti-islet cell and anti-GAD antibody levels and DKA risk stratification to allow the timely initiation of insulin and prevent further complications. Presentation: Thursday, June 15, 2023

The use of multiple daily injections versus insulin pump therapy for HgbA1c reduction in patients with insulin-dependent type 2 diabetes.

More than 35 million Americans live with type 2 diabetes (T2D), resulting in the need for newer strategies and technologies to manage the disease. Insulin pump therapy (IPT) has historically been reserved for type 1 diabetes, although emerging data demonstrates improved glucose outcomes for patients with T2D using IPT. To measure the change in HgbA1c in patients with T2D after changing therapy from multiple daily injections (MDI) to continuous subcutaneous insulin infusion through IPT. A retrospective comparison study was conducted by reviewing the electronic medical record of patients with T2D, older than 18 years, who had been on multiple daily insulin injections for at least 1 year, followed by IPT for at least 1 year. One hundred seventy-one patients met the inclusion criteria. There was a statistically significant reduction in mean HgbA1c from 9.6% to 7.6%. Insulin pump therapy may result in lower HgbA1c levels for T2D not at goal on MDI. Patients on multiple daily insulin injections who are not at goal should be considered for IPT.

High incidence of skin reactions secondary to the use of adhesives in glucose sensors or insulin pumps for the treatment of children with type 1 diabetes

AimsTo evaluate the incidence of the skin reactions secondary to continuous subcutaneous insulin infusion (CSII) or continuous glucose monitoring (CGM), sensors and the characteristics of affected children with type 1 diabetes. MethodsAn observational, retrospective, single-centre study included 198 children with type 1 diabetes, (46% girls, mean age 11.75 years). A standardised questionnaire was completed with the patient during current care to evaluate the skin reactions (mean and percentage), the type of reaction, their impact and the treatment) and the characteristics of affected children with univariate and multivariate analysis. ResultsSixty-seven children (33.8%) reported active skin reactions: 45 children with CSII (30.4%) and 46 with CGM (23.5%). Children with skin reactions were younger (mean age 10.6 yo versus 12.34 yo, p < 0.05), with a younger age at the diagnosis of diabetes (5.59 yo versus 7.08 yo, p < 0.05). Atopy was more frequent in the group with skin reactions (76.1% versus 54.1% p < 0.05). On multivariate analysis, only the personal history of atopy was associated with skin reactions: OR 2.56 [1.16–5.97] (p < 0.05). ConclusionThis study confirms the high incidence of skin reactions to adhesive devices used in the treatment of type 1 diabetes in children.

Pharmacoepidemiological analysis of type 1 diabetes mellitus insulin therapy (According to the Moscow segment of the State Register of Diabetes Mellitus)

BACKGROUND: When developing programs for state reimbursement of the cost of medical services and medicines, when providing assistance to patients suffering from type 1 diabetes mellitus (DM1), data based on the results of pharmacoepide-miological studies (FEI) conducted in real clinical practice of treating patients are needed. The obtained results of the analysis of drug consumption allow us to study the most commonly used insulin therapy regimens and their compliance with modern clinical recommendations. Calculations of the weighted average cost of conducting hypoglycemic therapy in DM1 can be used for further pharmacoeconomical calculations, including analysis of the medical and social cost of the disease.AIM: To conduct a pharmacoepidemiological analysis of the consumption of insulin preparations according to the ATX /DDD methodology, to study the modes of insulin administration and the ratio of the weighted average cost of insulin therapy components per 1 patient with DM1 per year in the outpatient practice of treatment with the introduction of insulin in the mode of multiple injections of insulin (MII) and during continuous subcutaneous insulin infusion (CSII).MATERIALS AND METHODS: A retrospective continuous cohort analytical pharmacoepidemiological study was conducted on the basis of the SRDM database (status as of 01/01/2020), in which 17,617 patients with T1DM aged 18 years and older were registered at the time of the study.RESULTS: 90% of patients received analogues of human insulin in the MII mode using syringe pens, 8.6% used the CSII mode. In 34.5% of patients with DM1 HbA1c was &lt;7%, the proportion of patients with HbA1c &gt;8% was 28%. The average cost of insulin therapy per 1 person per year was 54,977 rubles. The cost of basal insulin treatment per 1 patient per year was approximately 1.5 times higher than the cost of bolus insulin during insulin therapy in the MII mode (33,960 rubles and 21,017 rubles, respectively). The weighted average cost of insulin per 1 patient per year for CSII was 31,822 rubles.CONCLUSION: The majority of patients with DM1 in the study cohort received analogues of human insulin in the basic bolus mode of MII using syringe pens, which corresponds to existing clinical recommendations. The proportion of patients achieving the goals of glycemic control is comparable to the data obtained on the basis of registers of diabetic patients in other economically developed countries

Expected Basal Insulin Requirement during CSII therapy by Age Group, Sex and BMI, based on 25,718 Young People with Type 1 Diabetes in the DPV Registry.

Background Since the introduction of insulin pumps into the therapy of paediatric subjects, different approaches have been taken to find optimal basal rates. Previously, the DPV registry provided circadian basal rate patterns for different age groups. As the number of pump users has increased recently and short-acting insulin analogues are now predominant, we performed a new analysis with a larger data pool. Methods We included all recent basal profiles from T1D patients between 1 and 25 years from the DPV 2021 data pool. We excluded night-time-only pump users, human regular insulin users, and daily basal rates < 0.05 U/kgBW/d and >1.0 U/kgBW/d. Results In the analysis of profiles from 25,718 young persons with T1D, differences in the daily pattern of basal rates were found between age groups. In addition, we saw significant (p<0.001) differences in total daily basal dose between genders in all age groups except adults. In addition, the shape of the expected basal-rate pattern differed by BMI, HbA1c and use of continuous glucose monitoring. Discussion This analysis demonstrates multiple factors influencing basal patterns and insulin requirement, including age group, gender, overweight, HbA1c, bolus frequency and sensor use. As circadian basal rates are still mandatory for initiating insulin pump therapy with or without automation, a multimodal approach is necessary to estimate optimal basal rates.

Effects of Type 1 Diabetes Mellitus on Linear Growth: A Comprehensive Review.

Type 1 diabetes mellitus (T1DM) has a significant effect on the growth of children. The disease has a negative effect on growth when considered in relation to the time period and metabolic control. Studies in this review have suggested debilitated growth in children with T1DM and have a few anomalies in the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis when compared to fit children. Some studies show that children with T1DM were taller before the onset of the disease and during early diagnosis. Moreover, the linear growth depends on the interaction between the gonadotropin hormone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex steroid hormones axis and GH-IGF-1; there's a rise in GH during puberty, which has an effect on the estrogen and testosterone, which leads to the pulsatile secretion of GH, this increment leads to insulin resistance. These studies suggest short stature in girls, and some suggest in both. The final height in boys was unchanged, but a slight decline was observed in girls. This review aims to provide the latest understanding of impaired heightin children with T1DM. The most accepted and effective treatment of impaired growth is the administration of long-acting insulin or continuous rapid-acting insulin. However, height was affected by the administration of good basal insulin at puberty and was unaffected by the continuous subcutaneous insulin injection. Hence, new technologies are the therapeutic regimen in children, especially the prepubertal age group; it will be interesting to see their effects on growth patterns in these children with T1DM.

Case Report: Chest Pain as an Uncommon Presentation for Euglycemic Diabetic Ketoacidosis in a Female Patient Using SGLT2 inhibitor

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are well-recognised antidiabetic medications among clinicians due to its highly protective effects on cardiovascular and renal systems on diabetic patients. However, one of its uncommonly reported side effects is the development of euglycemic diabetic ketoacidosis (EuDKA) which is characterized by mild hyperglycemia, ketosis and acidosis. Chest pain as a clinical presentation of EuDKA has been rarely reported in the literature. We present a case of a 46-year-old female with a past medical history of type 2 diabetes mellitus (T2DM), hypertension, and hypertriglyceridemia presented to the hospital with central chest pain that radiates to the back and is associated with mild shortness of breath and one bout of vomiting. She had been taking dapagliflozin, an SGLT2 inhibitor, for four years. She was found to have a blood glucose level of 7 mmol\L, high anion gap metabolic acidosis and ketonuria. Toxicology screening was unremarkable. She was diagnosed as a case of SGLT2-induced EuDKA and was treated with fluid, insulin and potassium chloride (KCL). Her hospital course went smoothly. Dapagloflzi was discontinued, and she was discharged home on oral metformin and subcutaneous insulin. This study highlights the rare occurance of chest pain as a presentation of EuDKA, an uncommon side effect of the widely used SGLT2 inhibitors. Chest pain in patients using SGLT2 Inhibitors should raise the clinician's suspicion for possible EuDKA.

Advantages of sensor-augmented insulin pump therapy for pregnant women with type 1 diabetes mellitus.

To evaluate the efficacy of sensor-augmented pump (SAP) for improving obstetric and neonatal outcomes among pregnant women with type 1 diabetes mellitus by comparing it with continuous subcutaneous insulin infusion plus self-monitoring of blood glucose (continuous subcutaneous insulin infusion [CSII]/SMBG). This retrospective cohort study included 40 cases of pregnancy complicated by type 1 diabetes mellitus treated with SAP (SAP group), and 29 cases of pregnancy complicated by type 1 diabetes mellitus treated with CSII/SMBG (CSII/SMBG group). The obstetric and neonatal outcomes were compared between the two groups. The median of the glycoalbumin levels in the first (18.8% vs 20.9%; P < 0.05) and second (15.4% vs 18.0%; P < 0.05) trimesters, the hemoglobin A1c levels in the peripartum period (6.1% vs 6.5%; P < 0.05) and the standard deviation score of birthweights (0.36 vs 1.52; P < 0.05) were significantly lower in the SAP group than in the CSII/SMBG group. The incidence rate of large for gestational age newborns was significantly lower in the SAP group than in the CSII/SMBG group (27.5% vs 65.5%; P < 0.05). No significant differences in the incidence rates of hypertensive disorders of pregnancy, small for gestational age, respiratory distress syndrome, neonatal hypoglycemia, hypervolemia and hyperbilirubinemia were observed between the groups. The present study showed that SAP therapy is more effective in preventing large for gestational age newborns in pregnant women with type 1 diabetes mellitus than CSII/SMBG.

Monitoring Statistical Properties of Kalman Filter Residuals in an Artificial Pancreas to Detect Overnight Pump Malfunctions Causing Insulin Suspension

Continuous Subcutaneous Insulin Infusion (CSII) pumps are essential components in a closed-loop insulin delivery system (the so-called artificial pancreas), a recent therapeutic option for type 1 diabetes management. The efficacy of glucose regulation obtained by such a system might be severely compromised if the pump fails, possibly putting the patient’s safety at risk. Therefore, reliable and timely detection of these malfunctions is of critical practical importance. For this reason, in this study we present a novel algorithm specifically designed to detect overnight pump malfunctions resulting in insulin suspension. This algorithm adopts a real-time model-based approach and builds upon our team’s previous work, which relied solely on the magnitude of prediction residuals. In contrast, our current contribution extends the fault detection strategy by incorporating a comprehensive analysis of various statistical properties associated with the residuals. These properties encompass not only the magnitude but also the sample mean, median, variance, power, and other statistics related to the whiteness of the residuals. The considered linear black-box patients’ models have been individualized by estimating the model parameters on seven days of each patient’s data. Subsequently, the model is used in a Kalman filter to generate the predicted glucose levels with their confidence intervals. The effectiveness of the new strategy is compared to the previously proposed approach on an in-silico dataset generated by the UVa/Padova Type 1 Diabetes simulator, which has been accepted by the US Food and Drug Administration as a substitute for animal testing prior to human clinical trials with an artificial pancreas. The best performing detection strategy is based on the sign-sum test and achieves a recall of 91.3%, while generating less than 1 false alarm every 10 days. This improves the performance of our previous contribution that exhibits a comparable number of false alarms, but an overall lower recall metric, equal to 82.7%. The proposed algorithm is designed to complement other dedicated modules within the system, aiming to detect malfunctions related to glucose sensors (such as missed samples and pressure-induced sensitivity losses) as well as human errors (including missed meal announcements). A robustness analysis has been conducted to examine the performance of the algorithm in the presence of these additional anomalies. The results of these analyses demonstrated that the proposed algorithm maintains its sensitivity to pump malfunctions while exhibiting only a marginal increase in false alarms.

Glycometabolic outcomes in adult type 1 diabetic patients switching to closed-loop systems

ObjectiveThis study aimed to evaluate glycometabolic outcomes in AID technology-naïve T1D patients after switching to Hybrid Closed Loop (HCL) and Advanced Hybrid Closed Loop (AHCL) systems. Research design and methodsThis was a 12-month, prospective, observational, two-center study on 54 type 1 diabetes (T1D) patients aged 19–65 years managed with multiple daily injections (MDI) or Continuous Subcutaneous Insulin Infusion (CSII) in open-loop to evaluate the superiority in terms of effectiveness and safety of Automated Insulin Delivery (AID) systems. ResultsHbA1c levels significantly improved at the end of the study. Time spent with glucose levels in target range (TIR70-180 mg/dL, 3.9-10 mmol/L) increased from 50.5 ± 15.6% at baseline to 73.6 ± 8.0% at 12 months (p < 0.001); time spent above range (TAR180-250 mg/dL, 10-13.9 mmol/L and TAR≥250 mg/dL, 13.9 mmol/L) decreased from 30.6 ± 9.0% and 14.2 ± 10.2 at baseline to 19.3 ± 5.3% and 4.8 ± 3.3% at 12 months (p < 0.001 for both), respectively; time spent below range (TBR54-69 mg/dL, 3-3.8 mmol/L and TBR<54 mg/dL, 3.0 mmol/L) decreased from 3.5 ± 2.6% and 1.2 ± 1.4% at baseline to 1.9 ± 1.5% and 0.4 ± 0.7% at the end of the study (p < 0.001 for both); coefficient of variation (CV) decreased from 35.9 ± 7.8% at baseline to 33.0 ± 5.3% (p < 0.05). Satisfaction with the new technology was scored as high. ConclusionAID-naïve T1D patients switching to HCL/AHCL systems have significantly and safely improved their glycometabolic outcomes with their high satisfaction with the new type of treatment.

Association between different modalities of insulin administration and metabolic dysfunction-associated fatty liver disease in adults with type 1 diabetes mellitus

AimWe examined whether different insulin administration modalities, i.e., multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII by insulin pumps), are differently associated with the risk of having metabolic dysfunction-associated fatty liver disease (MAFLD), with or without coexisting significant liver fibrosis (assessed by validated non-invasive biomarkers), in adults with type 1 diabetes mellitus (T1DM). MethodsWe conducted a retrospective, multicenter, cross-sectional study involving 1,417 adult individuals with established T1DM treated with MDI or CSII. We calculated hepatic steatosis index (HSI) and fibrosis (FIB)-4 index for non-invasively detecting MAFLD (defined by HSI >36), with or without coexisting significant fibrosis (defined by FIB-4 index ≥ 1.3 or <1.3, respectively). ResultsCompared to the MDI group (n = 1,161), insulin-pump users (n = 256; 18.1%) were more likely to be younger (mean age: 40 vs. 48 years, P < 0.001), had better glycemic control (mean hemoglobin A1c: 7.7% vs. 7.9%, P = 0.025) and a markedly lower prevalence of MAFLD with coexisting significant fibrosis (2.7% vs. 8.1%, P = 0.010), but a comparable prevalence of MAFLD without fibrosis. In multinomial logistic regression analysis, CSII therapy was associated with a ∼70%-lower risk of MAFLD with significant fibrosis (unadjusted odds ratio 0.32, 95% confidence interval 0.14–0.70; P = 0.004), but this association was no longer significant after adjustment for age, hemoglobin A1c and other potential confounders. ConclusionThe lower prevalence of MAFLD with coexisting significant fibrosis we observed in adults with T1DM using CSII therapy, compared to those using MDI therapy, is primarily mediated by inter-group differences in age.

Treatment of diabetic ketoacidosis with subcutaneous regular insulin in a non-ICU setting is effective and economical: A single-center experience

Treatment of diabetic ketoacidosis with subcutaneous regular insulin in a non-ICU setting is effective and economical: A single-center experience

Psychosocial and Glycemic Benefits for Insulin-Using Adults With Type 2 Diabetes After Six Months of Pump Therapy: A Quasi-Experimental Approach.

Continuous subcutaneous insulin infusion (CSII) use in adults with type 1 diabetes offers psychosocial and clinical benefits, but little is known about its impact on such outcomes in the type 2 diabetes (T2D) population. To address this gap, we conducted a quasi-experimental prospective study to assess psychosocial, glycemic, and behavioral changes over six months in T2D adults on multiple daily injections (MDI) who were interested in starting Omnipod DASH, comparing those who did versus did not start on it. In total, 458 adults with T2D completed baseline questionnaires assessing psychosocial dimensions (eg, diabetes distress), clinical metrics (eg, HbA1c [glycosylated hemoglobin]), and behavioral measures (eg, missed mealtime boluses). Six months later, 220 (48.0%) completed the same questionnaire again. To examine differences in outcomes over time between those who began CSII (n = 176) versus those who remained on MDI (n = 44), a latent change score approach was used. The CSII users reported greater gains than MDI users on all major psychosocial metrics, including overall well-being (P < .001) diabetes distress (P < .001), perceived T2D impact on quality of life (P = .003), and hypoglycemic worries and concerns (P < .001). The CSII users similarly reported a larger decline in HbA1c than MDI users (P < .05) and greater declines in two critical self-care behaviors: number of missed mealtime boluses (P < .001) and number of days of perceived overeating (P = .001). The introduction of CSII (Omnipod DASH) in T2D adults can contribute to significant psychosocial, glycemic, and behavioral benefits, indicating that broader use of CSII in the T2D population may be of value.

Ultrasound Detected Subcutaneous Changes in a Pediatric Cohort After Initiation of a New Insulin Pump or Glucose Sensor.

Objective: This study examined subcutaneous tissue changes at sites used by continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM), and tested whether these changes, if any, were associated with glycated hemoglobin (HbA1c). Research Design and Methods: This prospective study investigated recently used CSII or CGM sites in 161 children and adolescents during the first year after initiation of a new diabetes device. Subcutaneous changes such as echogenicity, vascularization, and the distance from the skin surface to the muscle at CSII and CGM sites were assessed by ultrasound. Results: The distance from skin surface to muscle fascia at both the upper arm and abdomen was influenced by age, body mass index z-score, and sex. Especially in boys and the youngest, the depth of many devices outreached the mean distance. The mean distance for boys at the abdomen and upper arm ranged from 4.5-6.5 mm and 5-6.9 mm for all ages, respectively. Hyperechogenicity at CGM sites was 4.3% after 12 months. The frequency of subcutaneous hyperechogenicity and vascularization at CSII sites increased significantly over time (41.2% to 69.3% and 2% to 16% respectively, P < 0.001 and P = 0.009). Hyperechogenicity in the subcutis was not a predictor of elevated HbA1c (P = 0.11). Conclusion: There is large variation in the distance from the skin surface to the muscle fascia and many diabetes devices reach even deeper. Hyperechogenicity and vascularization increased significantly over time at CSII sites, but not CGM sites. The importance of hyperechogenicity for insulin absorption is unclear and further investigations are needed. Clinical Trial Registration number: NCT04258904.

Characteristics of pregnancy complicated with type 1 and type 2 diabetes.

Diabetes in pregnancy is a major risk factor for adverse perinatal outcomes such as congenital anomalies, hypertensive disorders of pregnancy (HDP), and macrosomia. For the mechanism of onset of type 1 and type 2 diabetes are different, we focused on the difference in perinatal outcomes between the type 1 and type 2 diabetes groups. We retrospectively reviewed 22 pregnancies with type 1 diabetes and 15 pregnancies with type 2 diabetes, who were managed in our single center, with regard to maternal diabetes conditions during pregnancy and neonatal birthweight and blood glucose level. Furthermore, we checked the effect of continuous glucose monitoring and continuous subcutaneous insulin injection in pregnancies with type 1 diabetes. Type 1 diabetes in pregnancy was less controllable and increased neonatal birth weight and neonatal hypoglycemia within 2h after birth after neonatal care unit admission. Continuous glucose monitoring and continuous subcutaneous insulin injection that are convenient to use, had a similar effect in the management of type 1 diabetes during pregnancy, compared with conventional diabetes treatment. In contrast, maternal BMI and HDP were increased in women with type 2 diabetes. In the management of pregnancy with diabetes, we should pay attention to the difference in pregnancy prognosis between type 1 and type 2 diabetes.

Effects of applications manual pressure and shotblocker to reduce needle-related pain and fear in children with type 1 diabetes mellitus

BackgroundPain and fear associated with insulin injections can cause children with type 1 diabetes mellitus to avoid insulin injections and skip doses. ObjectiveTo evaluate and compare pain and fear levels in children aged 6–12 years receiving subcutaneous insulin injection using the manual pressure and ShotBlocker methods. MethodsA randomized controlled study was conducted with 90 children with type 1 diabetes who were allocated using block randomization to the manual pressure, ShotBlocker, and control groups (n = 30 in each group). Fear and pain levels were rated by the children, their parents, and a member of the study team immediately before and after insulin injection using the Children's Fear Scale and Wong-Baker Faces Pain Rating Scale, respectively. ResultsAll groups had similar self-, parent-, and researcher-reported levels of preprocedural pain and fear (p > 0.05). However, pain and fear scores were lower in the manual pressure and ShotBlocker groups than in the control group after injection (p = 0.0001). There was no significant difference in pain and fear scores between the two intervention groups (p > 0.05). ConclusionManual pressure and the ShotBlocker both reduced fear and pain associated with insulin injection in 6- to 12-year-old children with type 1 diabetes. Implications for practiceBoth the manual pressure and ShotBlocker methods can easily be applied in children receiving insulin injections. As manual pressure is completely cost- and equipment-free, it is a useful option to reduce pain and fear related to insulin injection.Clinical Trial Registration Number: National Institutes of Health (NIH), ClinicalTrials.gov, NCT05789810.

Enhancing oral bioavailability of insulin through bilosomes: Implication of charge and chain length on apical sodium-dependent bile acid transporter (ASBT) uptake

This study investigates the impact of charge and chain length of bile salts in the bilosomes on the oral bioavailability of insulin (IN) by examining their uptake via the apical sodium-dependent bile acid transporter (ASBT). Deoxycholic acid bile salt was conjugated with different amino acids to create conjugates with varying charge and chain length, which were then embedded in liposomes. The resulting bilosomes had a particle size <400 nm, a PDI of 0.121 ± 0.03, and an entrapment efficiency of ∼70 %, while maintaining the chemical and conformational integrity of the loaded IN. Bilosomes also provided superior protection in biological fluids without compromising their biophysical attributes. Quantitative studies using the Caco-2 cell line demonstrated that anionic bilosomes were taken up more efficiently through ASBT than cationic bilosomes with 4- and 1.3-fold increase, respectively. Ex-vivo permeability studies corroborated these findings. In-vivo efficacy studies revealed a 1.6-fold increase in the AUC of IN with bilosomes compared to subcutaneous IN. The developed bilosomes were able to reduce blood glucose levels by ∼65 % at 6 h, with a cumulative hypoglycemic value of 35 % and a BAR of ∼30 %. These results suggest that ASBT can be a suitable target for improving the oral bioavailability of bilosomes containing IN.

Quality of Life and Treatment Satisfaction In Type I Diabetic Patients Treated with Subcutaneous Insulin Multiple Daily Injections

Background: Diabetes represents a major health problem because of its high prevalence, morbidity and mortality, its influence on patient quality of life and its impact on the health system. This impact involves the physical and emotional overload of diabetes, a disease that requires life-long treatment, including lifestyle and pharmacological measures, often with multiple drugs. Quality of life QOL is regarded as a subjective measure of health and well-being related to a disease. Treatment satisfaction is a subjective measure that evaluates the patient's experience of the processes and results of treatment. Furthermore, it is understood that poor satisfaction with treatment compromises treatment adherence. Aim: The aim of this case-control study was to determine and explore the quality of life QOL and treatment satisfaction in patients with Type 1 diabetes (T1DM) treated with subcutaneous insulin multiple daily injections (MDI). Subjects and Method: Consecutive patients aged between 18 and 55 years, and attending diabetes clinics for a routine visit, completed a pre-validated questionnaire created from the Diabetes-Specific Quality-of-Life Scale (DSQOLS), the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the SF-36 Health Survey (SF-36). Results: The result of this study shows that there is no difference in distribution between genders; 53.3% males and 46.7 females. Moreover, the largest percentage of age was between 46-55 (50%). Patient satisfaction presented at a higher percentage in males 81.3%, graduates 40% and patients aged 26-35 (80.0%). Conclusion: To conclude, diabetes Type 1 is a common condition and is considered a significant public health concern that significantly increases the risk of health problems. Health-related quality of life (HRQOL) is considered a multi-dimensional concept that includes domains related to the effect of both physical and mental health perception and their correlates such as the health risks and conditions.